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1. SUCCOR Nodes: May Sentinel Node Biopsy Determine the Need for Adjuvant Treatment?

Author

Berasaluce Gomez, A, Martin-Calvo, N, Boria, F, Manzour, N, Chacon, E, Bizzarri, N, Chiva, L, Martinez, A, Quesada, A, Kucukmetin, A, Vazquez, A, Mandic, A, Casajuana, A, Kavallaris, A, Fagotti, A, Perrone, A, Ferrero, A, Lekuona, A, Uppin, A, Stepanyan, A, Chiofalo, B, Morillas, B, Tauste, C, Andrade, C, Mom, C, Brucker, C, Sarac, C, Vazquez-Vicente, D, Cibula, D, Querleu, D, Erasun, D, Kaidarova, D, Tsolakidis, D, Haidopoulos, D, Golub, D, Bonci, E, Aksahin, E, Goncalves, E, Moratalla, E, Karaman, E, Myriokefalitaki, E, Ghezzi, F, Narducci, F, Roldan, F, Raspagliesi, F, Goffin, F, Grandjean, F, Guyon, F, Demirkiran, F, Fiol, G, Chakalova, G, Mancebo, G, Vorgias, G, Gebauer, G, Meili, G, Hernandez-Cortes, G, Bogani, G, Cordeiro, G, Vujic, G, Mendinhos, G, Trum, H, Bonsang-Kitzis, H, Haller, H, Vergote, I, Zapardiel, I, Aluloski, I, Berlev, I, Pete, I, Kalogiannidis, I, Kotsopoulos, I, Yezhova, I, Diez, J, Feron, J, Scharf, J, Beltman, J, Haesen, J, Ponce, J, Cea, J, Minguez, J, Garcia, J, Arevalo-Serrano, J, Gilabert, J, Alcazar, J, Kukk, K, Galaal, K, Cardenas, L, Pirtea, L, Mereu, L, Anchora, L, Dostalek, L, Klasa, L, Pakizimre, M, Undurraga, M, Jedryka, M, Bernardino, M, Alonso-Espias, M, Martin-Salamanca, M, Cuadra, M, Tavares, M, Malzoni, M, Fehr, M, Luyckx, M, Lanner, M, Leht, M, Meydanli, M, Mallmann, M, Capilna, M, Redecha, M, Mitrovic, M, Maenpaa, M, Guijarro, M, Abdalla, N, Gomes, N, Povolotskaya, N, Badzakov, N, Arencibia, O, Akbayir, O, Cavalle, P, Zusterzeel, P, Rolland, P, Coronado, P, Bharathan, R, Saaron, R, Sousa, R, Fruscio, R, Jach, R, Poka, R, Barrachina, R, Domingo, S, Morales, S, Akgol, S, Fernandez-Gonzalez, S, Aliyev, S, Herrero, S, Fidalgo, S, Prader, S, Smrkolj, S, Petousis, S, Kovachev, S, Turan, T, Toptas, T, Castellanos, T, da Costa, T, Marina, T, Zanagnolo, V, Martin, V, Gonzalez, V, Student, V, Sukhin, V, Berasaluce Gomez A., Martin-Calvo N., Boria F., Manzour N., Chacon E., Bizzarri N., Chiva L., Martinez A., Quesada A., Kucukmetin A., Vazquez A., Mandic A., Casajuana A., Kavallaris A., Fagotti A., Perrone A., Ferrero A., Lekuona A., Uppin A., Stepanyan A., Chiofalo B., Morillas B., Tauste C., Andrade C., Mom C., Brucker C., Sarac C. -P., Vazquez-Vicente D., Cibula D., Querleu D., Erasun D., Kaidarova D., Tsolakidis D., Haidopoulos D., Golub D., Bonci E. -A., Aksahin E., Goncalves E., Moratalla E., Karaman E., Myriokefalitaki E., Ghezzi F., Narducci F., Roldan F., Raspagliesi F., Goffin F., Grandjean F., Guyon F., Demirkiran F., Fiol G., Chakalova G., Mancebo G., Vorgias G., Gebauer G., Meili G., Hernandez-Cortes G., Bogani G., Cordeiro G., Vujic G., Mendinhos G., Trum H., Bonsang-Kitzis H., Haller H., Vergote I., Zapardiel I., Aluloski I., Berlev I., Pete I., Kalogiannidis I., Kotsopoulos I., Yezhova I., Diez J., Feron J. G., Scharf J. -P., Beltman J., Haesen J., Ponce J., Cea J., Minguez J. A., Garcia J., Arevalo-Serrano J., Gilabert J., Alcazar J. L., Kukk K., Galaal K., Cardenas L., Pirtea L., Mereu L., Anchora L. P., Dostalek L., Klasa L., PakizImre M., Undurraga M., Jedryka M., Bernardino M., Alonso-Espias M., Martin-Salamanca M. B., Cuadra M., Tavares M., Malzoni M., Fehr M., Luyckx M., Lanner M., Leht M., Meydanli M., Mallmann M., Capilna M., Redecha M., Mitrovic M., Maenpaa M. M., Guijarro M., Abdalla N., Gomes N., Povolotskaya N., Badzakov N., Arencibia O., Akbayir O., Cavalle P., Zusterzeel P., Rolland P., Coronado P., Bharathan R., Saaron R., Sousa R., Fruscio R., Jach R., Poka R., Barrachina R., Domingo S., Morales S., Akgol S., Fernandez-Gonzalez S., Aliyev S., Herrero S., Fidalgo S., Prader S., Smrkolj S., Petousis S., Kovachev S., Turan T., Toptas T., Castellanos T., da Costa T. D., Marina T., Zanagnolo V., Martin V., Gonzalez V., Student V., Sukhin V., Berasaluce Gomez, A, Martin-Calvo, N, Boria, F, Manzour, N, Chacon, E, Bizzarri, N, Chiva, L, Martinez, A, Quesada, A, Kucukmetin, A, Vazquez, A, Mandic, A, Casajuana, A, Kavallaris, A, Fagotti, A, Perrone, A, Ferrero, A, Lekuona, A, Uppin, A, Stepanyan, A, Chiofalo, B, Morillas, B, Tauste, C, Andrade, C, Mom, C, Brucker, C, Sarac, C, Vazquez-Vicente, D, Cibula, D, Querleu, D, Erasun, D, Kaidarova, D, Tsolakidis, D, Haidopoulos, D, Golub, D, Bonci, E, Aksahin, E, Goncalves, E, Moratalla, E, Karaman, E, Myriokefalitaki, E, Ghezzi, F, Narducci, F, Roldan, F, Raspagliesi, F, Goffin, F, Grandjean, F, Guyon, F, Demirkiran, F, Fiol, G, Chakalova, G, Mancebo, G, Vorgias, G, Gebauer, G, Meili, G, Hernandez-Cortes, G, Bogani, G, Cordeiro, G, Vujic, G, Mendinhos, G, Trum, H, Bonsang-Kitzis, H, Haller, H, Vergote, I, Zapardiel, I, Aluloski, I, Berlev, I, Pete, I, Kalogiannidis, I, Kotsopoulos, I, Yezhova, I, Diez, J, Feron, J, Scharf, J, Beltman, J, Haesen, J, Ponce, J, Cea, J, Minguez, J, Garcia, J, Arevalo-Serrano, J, Gilabert, J, Alcazar, J, Kukk, K, Galaal, K, Cardenas, L, Pirtea, L, Mereu, L, Anchora, L, Dostalek, L, Klasa, L, Pakizimre, M, Undurraga, M, Jedryka, M, Bernardino, M, Alonso-Espias, M, Martin-Salamanca, M, Cuadra, M, Tavares, M, Malzoni, M, Fehr, M, Luyckx, M, Lanner, M, Leht, M, Meydanli, M, Mallmann, M, Capilna, M, Redecha, M, Mitrovic, M, Maenpaa, M, Guijarro, M, Abdalla, N, Gomes, N, Povolotskaya, N, Badzakov, N, Arencibia, O, Akbayir, O, Cavalle, P, Zusterzeel, P, Rolland, P, Coronado, P, Bharathan, R, Saaron, R, Sousa, R, Fruscio, R, Jach, R, Poka, R, Barrachina, R, Domingo, S, Morales, S, Akgol, S, Fernandez-Gonzalez, S, Aliyev, S, Herrero, S, Fidalgo, S, Prader, S, Smrkolj, S, Petousis, S, Kovachev, S, Turan, T, Toptas, T, Castellanos, T, da Costa, T, Marina, T, Zanagnolo, V, Martin, V, Gonzalez, V, Student, V, Sukhin, V, Berasaluce Gomez A., Martin-Calvo N., Boria F., Manzour N., Chacon E., Bizzarri N., Chiva L., Martinez A., Quesada A., Kucukmetin A., Vazquez A., Mandic A., Casajuana A., Kavallaris A., Fagotti A., Perrone A., Ferrero A., Lekuona A., Uppin A., Stepanyan A., Chiofalo B., Morillas B., Tauste C., Andrade C., Mom C., Brucker C., Sarac C. -P., Vazquez-Vicente D., Cibula D., Querleu D., Erasun D., Kaidarova D., Tsolakidis D., Haidopoulos D., Golub D., Bonci E. -A., Aksahin E., Goncalves E., Moratalla E., Karaman E., Myriokefalitaki E., Ghezzi F., Narducci F., Roldan F., Raspagliesi F., Goffin F., Grandjean F., Guyon F., Demirkiran F., Fiol G., Chakalova G., Mancebo G., Vorgias G., Gebauer G., Meili G., Hernandez-Cortes G., Bogani G., Cordeiro G., Vujic G., Mendinhos G., Trum H., Bonsang-Kitzis H., Haller H., Vergote I., Zapardiel I., Aluloski I., Berlev I., Pete I., Kalogiannidis I., Kotsopoulos I., Yezhova I., Diez J., Feron J. G., Scharf J. -P., Beltman J., Haesen J., Ponce J., Cea J., Minguez J. A., Garcia J., Arevalo-Serrano J., Gilabert J., Alcazar J. L., Kukk K., Galaal K., Cardenas L., Pirtea L., Mereu L., Anchora L. P., Dostalek L., Klasa L., PakizImre M., Undurraga M., Jedryka M., Bernardino M., Alonso-Espias M., Martin-Salamanca M. B., Cuadra M., Tavares M., Malzoni M., Fehr M., Luyckx M., Lanner M., Leht M., Meydanli M., Mallmann M., Capilna M., Redecha M., Mitrovic M., Maenpaa M. M., Guijarro M., Abdalla N., Gomes N., Povolotskaya N., Badzakov N., Arencibia O., Akbayir O., Cavalle P., Zusterzeel P., Rolland P., Coronado P., Bharathan R., Saaron R., Sousa R., Fruscio R., Jach R., Poka R., Barrachina R., Domingo S., Morales S., Akgol S., Fernandez-Gonzalez S., Aliyev S., Herrero S., Fidalgo S., Prader S., Smrkolj S., Petousis S., Kovachev S., Turan T., Toptas T., Castellanos T., da Costa T. D., Marina T., Zanagnolo V., Martin V., Gonzalez V., Student V., and Sukhin V.

Abstract

Background: The SUCCOR cohort was developed to analyse the overall and disease-free survival at 5 years in women with FIGO 2009 stage IB1 cervical cancer. The aim of this study was to compare the use of adjuvant therapy in these women, depending on the method used to diagnose lymphatic node metastasis. Patients and Methods: We used data from the SUCCOR cohort, which collected information from 1049 women with FIGO 2009 stage IB1 cervical cancer who were operated on between January 2013 and December 2014 in Europe. We calculated the adjusted proportion of women who received adjuvant therapy depending on the lymph node diagnosis method and compared disease free and overall survival using Cox proportional-hazards regression models. Inverse probability weighting was used to adjust for baseline potential confounders. Results: The adjusted proportion of women who received adjuvant therapy was 33.8% in the sentinel node biopsy + lymphadenectomy (SNB+LA) group and 44.7% in the LA group (p = 0.02), although the proportion of positive nodal status was similar (p = 0.30). That difference was greater in women with negative nodal status and positive Sedlis criteria (difference 31.2%, p = 0.01). Here, those who underwent a SNB+LA had an increased risk of relapse [hazard ratio (HR) 2.49, 95% confidence interval (CI) 0.98–6.33, p = 0.056] and risk of death (HR 3.49, 95% CI 1.04–11.7, p = 0.042) compared with those who underwent LA. Conclusions: Women in this study were less likely to receive adjuvant therapy if their nodal invasion was determined using SNB+LA compared with LA. These results suggest a lack of therapeutic measures available when a negative result is obtained by SNB+LA, which may have an impact on the risk of recurrence and survival.

Published
2023

2. SUCCOR Risk: Design and Validation of a Recurrence Prediction Index for Early-Stage Cervical Cancer

Author

Manzour, N, Chiva, L, Chacon, E, Martin-Calvo, N, Boria, F, Minguez, J, Alcazar, J, Zanagnolo, V, Querleu, D, Capilna, M, Fagotti, A, Kucukmetin, A, Mom, C, Chakalova, G, Aliyev, S, Malzoni, M, Narducci, F, Arencibia, O, Raspagliesi, F, Toptas, T, Cibula, D, Kaidarova, D, Meydanli, M, Tavares, M, Golub, D, Perrone, A, Poka, R, Tsolakidis, D, Vujic, G, Jedryka, M, Zusterzeel, P, Beltman, J, Goffin, F, Haidopoulos, D, Haller, H, Jach, R, Yezhova, I, Berlev, I, Bernardino, M, Bharathan, R, Lanner, M, Sukhin, V, Feron, J, Fruscio, R, Kukk, K, Ponce, J, Abdalla, N, Akbayir, O, Akgol, S, Aksahin, E, Alonso-Espias, M, Aluloski, I, Andrade, C, Badzakov, N, Barrachina, R, Bogani, G, Bonci, E, Bonsang-Kitzis, H, Brucker, C, Cardenas, L, Casajuana, A, Cavalle, P, Cea, J, Chiofalo, B, Cordeiro, G, Coronado, P, Cuadra, M, Diez, J, da Costa, T, Domingo, S, Dostalek, L, Demirkiran, F, Erasun, D, Fehr, M, Fernandez-Gonzalez, S, Fidalgo, S, Fiol, G, Galaal, K, Garcia, J, Gebauer, G, Ghezzi, F, Gilabert, J, Gomes, N, Goncalves, E, Gonzalez, V, Grandjean, F, Guijarro, M, Guyon, F, Haesen, J, Hernandez-Cortes, G, Herrero, S, Pete, I, Kalogiannidis, I, Karaman, E, Kavallaris, A, Klasa, L, Kotsopoulos, I, Kovachev, S, Leht, M, Lekuona, A, Luyckx, M, Mallmann, M, Mancebo, G, Mandic, A, Marina, T, Martin, V, Martin-Salamanca, M, Martinez, A, Meili, G, Mendinhos, G, Mereu, L, Mitrovic, M, Morales, S, Moratalla, E, Morillas, B, Myriokefalitaki, E, Pakizimre, M, Petousis, S, Pirtea, L, Povolotskaya, N, Prader, S, Quesada, A, Redecha, M, Roldan, F, Rolland, P, Saaron, R, Sarac, C, Scharf, J, Smrkolj, S, Sousa, R, Stepanyan, A, Student, V, Tauste, C, Trum, H, Turan, T, Undurraga, M, Uppin, A, Vazquez, A, Vergote, I, Vorgias, G, Zapardiel, I, Manzour N., Chiva L., Chacon E., Martin-Calvo N., Boria F., Minguez J. A., Alcazar J. L., Zanagnolo V., Querleu D., Capilna M., Fagotti A., Kucukmetin A., Mom C., Chakalova G., Aliyev S., Malzoni M., Narducci F., Arencibia O., Raspagliesi F., Toptas T., Cibula D., Kaidarova D., Meydanli M., Tavares M., Golub D., Perrone A., Poka R., Tsolakidis D., Vujic G., Jedryka M., Zusterzeel P., Beltman J., Goffin F., Haidopoulos D., Haller H., Jach R., Yezhova I., Berlev I., Bernardino M., Bharathan R., Lanner M., Sukhin V., Feron J. G., Fruscio R., Kukk K., Ponce J., Abdalla N., Akbayir O., Akgol S., Aksahin E., Alonso-Espias M., Aluloski I., Andrade C., Badzakov N., Barrachina R., Bogani G., Bonci E. -A., Bonsang-Kitzis H., Brucker C., Cardenas L., Casajuana A., Cavalle P., Cea J., Chiofalo B., Cordeiro G., Coronado P., Cuadra M., Diez J., da Costa T. D., Domingo S., Dostalek L., Demirkiran F., Erasun D., Fehr M., Fernandez-Gonzalez S., Fidalgo S., Fiol G., Galaal K., Garcia J., Gebauer G., Ghezzi F., Gilabert J., Gomes N., Goncalves E., Gonzalez V., Grandjean F., Guijarro M., Guyon F., Haesen J., Hernandez-Cortes G., Herrero S., Pete I., Kalogiannidis I., Karaman E., Kavallaris A., Klasa L., Kotsopoulos I., Kovachev S., Leht M., Lekuona A., Luyckx M., Mallmann M., Mancebo G., Mandic A., Marina T., Martin V., Martin-Salamanca M. B., Martinez A., Meili G., Mendinhos G., Mereu L., Mitrovic M., Morales S., Moratalla E., Morillas B., Myriokefalitaki E., PakizImre M., Petousis S., Pirtea L., Povolotskaya N., Prader S., Quesada A., Redecha M., Roldan F., Rolland P., Saaron R., Sarac C. -P., Scharf J. -P., Smrkolj S., Sousa R., Stepanyan A., Student V., Tauste C., Trum H., Turan T., Undurraga M., Uppin A., Vazquez A., Vergote I., Vorgias G., Zapardiel I., Manzour, N, Chiva, L, Chacon, E, Martin-Calvo, N, Boria, F, Minguez, J, Alcazar, J, Zanagnolo, V, Querleu, D, Capilna, M, Fagotti, A, Kucukmetin, A, Mom, C, Chakalova, G, Aliyev, S, Malzoni, M, Narducci, F, Arencibia, O, Raspagliesi, F, Toptas, T, Cibula, D, Kaidarova, D, Meydanli, M, Tavares, M, Golub, D, Perrone, A, Poka, R, Tsolakidis, D, Vujic, G, Jedryka, M, Zusterzeel, P, Beltman, J, Goffin, F, Haidopoulos, D, Haller, H, Jach, R, Yezhova, I, Berlev, I, Bernardino, M, Bharathan, R, Lanner, M, Sukhin, V, Feron, J, Fruscio, R, Kukk, K, Ponce, J, Abdalla, N, Akbayir, O, Akgol, S, Aksahin, E, Alonso-Espias, M, Aluloski, I, Andrade, C, Badzakov, N, Barrachina, R, Bogani, G, Bonci, E, Bonsang-Kitzis, H, Brucker, C, Cardenas, L, Casajuana, A, Cavalle, P, Cea, J, Chiofalo, B, Cordeiro, G, Coronado, P, Cuadra, M, Diez, J, da Costa, T, Domingo, S, Dostalek, L, Demirkiran, F, Erasun, D, Fehr, M, Fernandez-Gonzalez, S, Fidalgo, S, Fiol, G, Galaal, K, Garcia, J, Gebauer, G, Ghezzi, F, Gilabert, J, Gomes, N, Goncalves, E, Gonzalez, V, Grandjean, F, Guijarro, M, Guyon, F, Haesen, J, Hernandez-Cortes, G, Herrero, S, Pete, I, Kalogiannidis, I, Karaman, E, Kavallaris, A, Klasa, L, Kotsopoulos, I, Kovachev, S, Leht, M, Lekuona, A, Luyckx, M, Mallmann, M, Mancebo, G, Mandic, A, Marina, T, Martin, V, Martin-Salamanca, M, Martinez, A, Meili, G, Mendinhos, G, Mereu, L, Mitrovic, M, Morales, S, Moratalla, E, Morillas, B, Myriokefalitaki, E, Pakizimre, M, Petousis, S, Pirtea, L, Povolotskaya, N, Prader, S, Quesada, A, Redecha, M, Roldan, F, Rolland, P, Saaron, R, Sarac, C, Scharf, J, Smrkolj, S, Sousa, R, Stepanyan, A, Student, V, Tauste, C, Trum, H, Turan, T, Undurraga, M, Uppin, A, Vazquez, A, Vergote, I, Vorgias, G, Zapardiel, I, Manzour N., Chiva L., Chacon E., Martin-Calvo N., Boria F., Minguez J. A., Alcazar J. L., Zanagnolo V., Querleu D., Capilna M., Fagotti A., Kucukmetin A., Mom C., Chakalova G., Aliyev S., Malzoni M., Narducci F., Arencibia O., Raspagliesi F., Toptas T., Cibula D., Kaidarova D., Meydanli M., Tavares M., Golub D., Perrone A., Poka R., Tsolakidis D., Vujic G., Jedryka M., Zusterzeel P., Beltman J., Goffin F., Haidopoulos D., Haller H., Jach R., Yezhova I., Berlev I., Bernardino M., Bharathan R., Lanner M., Sukhin V., Feron J. G., Fruscio R., Kukk K., Ponce J., Abdalla N., Akbayir O., Akgol S., Aksahin E., Alonso-Espias M., Aluloski I., Andrade C., Badzakov N., Barrachina R., Bogani G., Bonci E. -A., Bonsang-Kitzis H., Brucker C., Cardenas L., Casajuana A., Cavalle P., Cea J., Chiofalo B., Cordeiro G., Coronado P., Cuadra M., Diez J., da Costa T. D., Domingo S., Dostalek L., Demirkiran F., Erasun D., Fehr M., Fernandez-Gonzalez S., Fidalgo S., Fiol G., Galaal K., Garcia J., Gebauer G., Ghezzi F., Gilabert J., Gomes N., Goncalves E., Gonzalez V., Grandjean F., Guijarro M., Guyon F., Haesen J., Hernandez-Cortes G., Herrero S., Pete I., Kalogiannidis I., Karaman E., Kavallaris A., Klasa L., Kotsopoulos I., Kovachev S., Leht M., Lekuona A., Luyckx M., Mallmann M., Mancebo G., Mandic A., Marina T., Martin V., Martin-Salamanca M. B., Martinez A., Meili G., Mendinhos G., Mereu L., Mitrovic M., Morales S., Moratalla E., Morillas B., Myriokefalitaki E., PakizImre M., Petousis S., Pirtea L., Povolotskaya N., Prader S., Quesada A., Redecha M., Roldan F., Rolland P., Saaron R., Sarac C. -P., Scharf J. -P., Smrkolj S., Sousa R., Stepanyan A., Student V., Tauste C., Trum H., Turan T., Undurraga M., Uppin A., Vazquez A., Vergote I., Vorgias G., and Zapardiel I.

Abstract

Objective: Based on the SUCCOR study database, our primary objective was to identify the independent clinical pathological variables associated with the risk of relapse in patients with stage IB1 cervical cancer who underwent a radical hysterectomy. Our secondary goal was to design and validate a risk predictive index (RPI) for classifying patients depending on the risk of recurrence. Methods: Overall, 1116 women were included from January 2013 to December 2014. We randomly divided our sample into two cohorts: discovery and validation cohorts. The test group was used to identify the independent variables associated with relapse, and with these variables, we designed our RPI. The index was applied to calculate a relapse risk score for each participant in the validation group. Results: A previous cone biopsy was the most significant independent variable that lowered the rate of relapse (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.17–0.60). Additionally, patients with a tumor diameter >2 cm on preoperative imaging assessment (OR 2.15, 95% CI 1.33–3.5) and operated by the minimally invasive approach (OR 1.61, 95% CI 1.00–2.57) were more likely to have a recurrence. Based on these findings, patients in the validation cohort were classified according to the RPI of low, medium, or high risk of relapse, with rates of 3.4%, 9.8%, and 21.3% observed in each group, respectively. With a median follow-up of 58 months, the 5-year disease-free survival rates were 97.2% for the low-risk group, 88.0% for the medium-risk group, and 80.5% for the high-risk group (p < 0.001). Conclusion: Previous conization to radical hysterectomy was the most powerful protective variable of relapse. Our risk predictor index was validated to identify patients at risk of recurrence.

Published
2022

3. Adult primary cervical rhabdomyosarcomas: A Multicentric cross-national case series

Author

Ricciardi, E, Plett, H, Sangiorgio, V, Paderno, M, Landoni, F, Aletti, G, Prader, S, Du Bois, A, Harter, P, Colombo, N, Ricciardi E., Plett H., Sangiorgio V., Paderno M., Landoni F., Aletti G., Prader S., Du Bois A., Harter P., Colombo N., Ricciardi, E, Plett, H, Sangiorgio, V, Paderno, M, Landoni, F, Aletti, G, Prader, S, Du Bois, A, Harter, P, Colombo, N, Ricciardi E., Plett H., Sangiorgio V., Paderno M., Landoni F., Aletti G., Prader S., Du Bois A., Harter P., and Colombo N.

Abstract

Objectives: Adult primary cervical rhabdomyosarcoma is a very rare disease and data regarding treatment are sparce. The goal of this study was to report on our experience with the management of this rare entity, along with an evaluation of the literature. Methods: We conducted a review of the medical records at four centers from January 1990 to December 2017. We reviewed clinical characteristics including age at diagnosis, BMI, medical history and tumor stage, as well as treatment in the primary and recurrent settings and follow-up data. We reclassified tumors according to the Intergroup Rhabdomyosarcoma Study (IRS) clinical group. Results: A total of 15 patients were included in the analysis. Median age at diagnosis was 35 years (range 17-55). Median tumor size at presentation was 5 cm (range 3-10). Eleven patients had the embryonal variant, including five showing the botryoid subtype. Four patients had a pleomorphic rhabdomyosarcoma. Eleven patients had disease classified as IRS Clinical Group I, while the remaining four fell into groups II or III. Fertility-sparing treatment was offered to five patients. Primary treatment types were: surgery alone in eight patients, surgery followed by adjuvant chemotherapy in six patients, and neoadjuvant chemotherapy in two patients. The main risk factors for relapse were: IRS clinical group greater than I, tumor size greater than 5 cm, lymph nodal involvement, and non-embryonal histology. At a median follow-up of 35 months (range 3-282), we observed a 5-year overall survival rate of 78.2% and a progression-free survival of 58.2%. No patient in the IRS I group died of the disease. Three out of four patients in the IRS II-III group died of the disease (survival range 5-16 months following treatment). Conclusion: Our data show that cervical rhabdomyosarcomas account for at least two prognostic groups, demonstrating the existence of low-risk and high-risk patterns. The best predictor of prognosis appearsd to be the IRS clinical gr

Published
2020

4. Treatment of Multisystem Inflammatory Syndrome in Children

Author

McArdle A. J., Vito O., Patel H., Seaby E. G., Shah P., Wilson C., Broderick C., Nijman R., Tremoulet A. H., Munblit D., Ulloa-Gutierrez R., Carter M. J., De T., Hoggart C., Whittaker E., Herberg J. A., Kaforou M., Cunnington A. J., Levin M., Vazquez J. A., Carmona R., Perez L., Rubinos M., Veliz N., Yori S., Haerynck F., Hoste L., Leal I. A., Da Silva A. R. A., Silva A. E. A., Barchik A., Barreiro S. T. A., Cochrane N., Teixeira C. H., Arauj J. M., Ossa R. A. P. -D. L., Vieira C. S., Dimitrova A., Ganeva M., Stefanov S., Telcharova-Mihaylovska A., Biggs C. M., Scuccimarri R., Withington D., Raul B. B., Ampuero C., Aravena J., Casanova D., Cruces P., Diaz F., Garcia-Salum T., Godoy L., Medina R. A., Galaz G. V., Avila-Aguero M. L., Brenes-Chacon H., Ivankovich-Escoto G., Yock-Corrales A., Badib A., Badreldin K., Elkhashab Y., Heshmat H., Heinonen S., Angoulvant F., Belot A., Ouldali N., Beske F., Heep A., Masjosthusmann K., Reiter K., Heuvel I. V. D., Both U. V., Agrafiotou A., Antachopoulos C., Eleftheriou I., Farmaki E., Fotis L., Kafetzis D., Lampidi S., Liakopoulou T., Maritsi D., Michailidou E., Milioudi M., Mparmpounaki I., Papadimitriou E., Papaevangelou V., Roilides E., Tsiatsiou O., Tsolas G., Tsolia M., Vantsi P., Pineda L. Y. B., Aguilar K. L. B., Quintero E. M. C., Ip P., Kwan M. Y. W., Kwok J., Lau Y. L., To K., Wong J. S. C., David M., Farkas D., Kalcakosz S., Szekeres K., Zsigmond B., Aslam N., Andreozzi L., Bianco F., Bucciarelli V., Buonsenso D., Cimaz R., D'Argenio P., Dellepiane R. M., Fabi M., Mastrolia M. V., Mauro A., Mazza A., Romani L., Simonini G., Tipo V., Valentini P., Verdoni L., Reel B., Pace D., Torpiano P., Flores M. F., Dominguez M. G., Vargas A. L. G., Hernandez L. L., Figueroa R. P. M., Gaxiola G. P., Valadez J., Klevberg S., Knudsen P. K., Maseide P. H., Carrera J. M., Castano E. G., Timana C. A. D., Leon T. D., Estripeaut D., Levy J., Norero X., Record J., Rojas-Bonilla M., Iramain R., Hernandez R., Huaman G., Munaico M., Peralta C., Seminario D., Yarleque E. H. Z., Gadzinska J., Mandziuk J., Okarska-Napierala M., Alacheva Z. A., Alexeeva E., Ananin P. V., Antsupova M., Bakradze M. D., Bobkova P., Borzakova S., Chashchina I. L., Fisenko A. P., Gautier M. S., Glazyrina A., Kondrikova E., Korobyants E., Korsunskiy A. A., Kovygina K., Krasnaya E., Kurbanova S., Kurdup M. K., Mamutova A. V., Mazankova L., Mitushin I. L., Nargizyan A., Orlova Y. O., Osmanov I. M., Polyakova A. S., Romanova O., Samitova E., Sologub A., Spiridonova E., Tepaev R. F., Tkacheva A. A., Yusupova V., Zholobova E., Grasa C. D., Segura N. L., Martinon-Torres F., Melendo S., Echevarria A. M., Guzman J. M. M., Argueta J. R. P., Rivero-Calle I., Riviere J., Rodriguez-Gonzalez M., Rojo P., Manubens J. S., Soler-Palacin P., Soriano-Arandes A., Tagarro A., Villaverde S., Altman M., Brodin P., Horne A., Palmblad K., Brotschi B., Sauteur P. M., Schmid J. P., Prader S., Relly C., Schlapbach L. J., Seiler M., Truck J., Wutz D., Ketharanathan N., Vermont C., Ozkan E. A., Erdeniz E. H., Borisova G., Boychenko L., Diudenko N., Kasiyan O., Katerynych K., Melnyk K., Miagka N., Teslenko M., Trykosh M., Volokha A., Akomolafe T., Al-Abadi E., Alders N., Avram P., Bamford A., Bank M., Roy R. B., Beattie T., Boleti O., Broad J., Carrol E. D., Chandran A., Cooper H., Davies P., Emonts M., Evans C., Fidler K., Foster C., Gong C., Gongrun B., Gonzalez C., Grandjean L., Grant K., Hacohen Y., Hall J., Hassell J., Hesketh C., Hewlett J., Hnieno A., Holt-Davis H., Hossain A., Hudson L. D., Johnson M., Johnson S., Jyothish D., Kampmann B., Kavirayani A., Kelly D., Kucera F., Langer D., Lillie J., Longbottom K., Lyall H., MacKdermott N., Maltby S., McLelland T., McMahon A. -M., Miller D., Morrison Z., Mosha K., Muller J., Myttaraki E., Nadel S., Osaghae D., Osman F., Ostrzewska A., Panthula M., Papachatzi E., Papadopoulou C., Penner J., Polandi S., Prendergast A. J., Ramnarayan P., Rhys-Evans S., Riordan A., Rodrigues C. M. C., Romaine S., Seddon J., Shingadia D., Srivastava A., Struik S., Taylor A., Tran S., Tudor-Williams G., Van Der Velden F., Ventilacion L., Wellman P. A., Yanney M. P., Yeung S., Badheka A., Badran S., Bailey D. M., Burch A. K., Burns J. C., Cichon C., Cirks B., Dallman M. D., Delany D. R., Fairchok M., Friedman S., Geracht J., Langs-Barlow A., Mann K., Padhye A., Quade A., Ramirez K. A., Rockett J., Sayed I. A., Shahin A. A., Umaru S., Widener R., Angela M. H., Kandawasvika G., McArdle A.J., Vito O., Patel H., Seaby E.G., Shah P., Wilson C., Broderick C., Nijman R., Tremoulet A.H., Munblit D., Ulloa-Gutierrez R., Carter M.J., De T., Hoggart C., Whittaker E., Herberg J.A., Kaforou M., Cunnington A.J., Levin M., Vazquez J.A., Carmona R., Perez L., Rubinos M., Veliz N., Yori S., Haerynck F., Hoste L., Leal I.A., Da Silva A.R.A., Silva A.E.A., Barchik A., Barreiro S.T.A., Cochrane N., Teixeira C.H., Arauj J.M., Ossa R.A.P.-D.L., Vieira C.S., Dimitrova A., Ganeva M., Stefanov S., Telcharova-Mihaylovska A., Biggs C.M., Scuccimarri R., Withington D., Raul B.B., Ampuero C., Aravena J., Casanova D., Cruces P., Diaz F., Garcia-Salum T., Godoy L., Medina R.A., Galaz G.V., Avila-Aguero M.L., Brenes-Chacon H., Ivankovich-Escoto G., Yock-Corrales A., Badib A., Badreldin K., Elkhashab Y., Heshmat H., Heinonen S., Angoulvant F., Belot A., Ouldali N., Beske F., Heep A., Masjosthusmann K., Reiter K., Heuvel I.V.D., Both U.V., Agrafiotou A., Antachopoulos C., Eleftheriou I., Farmaki E., Fotis L., Kafetzis D., Lampidi S., Liakopoulou T., Maritsi D., Michailidou E., Milioudi M., Mparmpounaki I., Papadimitriou E., Papaevangelou V., Roilides E., Tsiatsiou O., Tsolas G., Tsolia M., Vantsi P., Pineda L.Y.B., Aguilar K.L.B., Quintero E.M.C., Ip P., Kwan M.Y.W., Kwok J., Lau Y.L., To K., Wong J.S.C., David M., Farkas D., Kalcakosz S., Szekeres K., Zsigmond B., Aslam N., Andreozzi L., Bianco F., Bucciarelli V., Buonsenso D., Cimaz R., D'Argenio P., Dellepiane R.M., Fabi M., Mastrolia M.V., Mauro A., Mazza A., Romani L., Simonini G., Tipo V., Valentini P., Verdoni L., Reel B., Pace D., Torpiano P., Flores M.F., Dominguez M.G., Vargas A.L.G., Hernandez L.L., Figueroa R.P.M., Gaxiola G.P., Valadez J., Klevberg S., Knudsen P.K., Maseide P.H., Carrera J.M., Castano E.G., Timana C.A.D., Leon T.D., Estripeaut D., Levy J., Norero X., Record J., Rojas-Bonilla M., Iramain R., Hernandez R., Huaman G., Munaico M., Peralta C., Seminario D., Yarleque E.H.Z., Gadzinska J., Mandziuk J., Okarska-Napierala M., Alacheva Z.A., Alexeeva E., Ananin P.V., Antsupova M., Bakradze M.D., Bobkova P., Borzakova S., Chashchina I.L., Fisenko A.P., Gautier M.S., Glazyrina A., Kondrikova E., Korobyants E., Korsunskiy A.A., Kovygina K., Krasnaya E., Kurbanova S., Kurdup M.K., Mamutova A.V., Mazankova L., Mitushin I.L., Nargizyan A., Orlova Y.O., Osmanov I.M., Polyakova A.S., Romanova O., Samitova E., Sologub A., Spiridonova E., Tepaev R.F., Tkacheva A.A., Yusupova V., Zholobova E., Grasa C.D., Segura N.L., Martinon-Torres F., Melendo S., Echevarria A.M., Guzman J.M.M., Argueta J.R.P., Rivero-Calle I., Riviere J., Rodriguez-Gonzalez M., Rojo P., Manubens J.S., Soler-Palacin P., Soriano-Arandes A., Tagarro A., Villaverde S., Altman M., Brodin P., Horne A., Palmblad K., Brotschi B., Sauteur P.M., Schmid J.P., Prader S., Relly C., Schlapbach L.J., Seiler M., Truck J., Wutz D., Ketharanathan N., Vermont C., Ozkan E.A., Erdeniz E.H., Borisova G., Boychenko L., Diudenko N., Kasiyan O., Katerynych K., Melnyk K., Miagka N., Teslenko M., Trykosh M., Volokha A., Akomolafe T., Al-Abadi E., Alders N., Avram P., Bamford A., Bank M., Roy R.B., Beattie T., Boleti O., Broad J., Carrol E.D., Chandran A., Cooper H., Davies P., Emonts M., Evans C., Fidler K., Foster C., Gong C., Gongrun B., Gonzalez C., Grandjean L., Grant K., Hacohen Y., Hall J., Hassell J., Hesketh C., Hewlett J., Hnieno A., Holt-Davis H., Hossain A., Hudson L.D., Johnson M., Johnson S., Jyothish D., Kampmann B., Kavirayani A., Kelly D., Kucera F., Langer D., Lillie J., Longbottom K., Lyall H., MacKdermott N., Maltby S., McLelland T., McMahon A.-M., Miller D., Morrison Z., Mosha K., Muller J., Myttaraki E., Nadel S., Osaghae D., Osman F., Ostrzewska A., Panthula M., Papachatzi E., Papadopoulou C., Penner J., Polandi S., Prendergast A.J., Ramnarayan P., Rhys-Evans S., Riordan A., Rodrigues C.M.C., Romaine S., Seddon J., Shingadia D., Srivastava A., Struik S., Taylor A., Tran S., Tudor-Williams G., Van Der Velden F., Ventilacion L., Wellman P.A., Yanney M.P., Yeung S., Badheka A., Badran S., Bailey D.M., Burch A.K., Burns J.C., Cichon C., Cirks B., Dallman M.D., Delany D.R., Fairchok M., Friedman S., Geracht J., Langs-Barlow A., Mann K., Padhye A., Quade A., Ramirez K.A., Rockett J., Sayed I.A., Shahin A.A., Umaru S., Widener R., Angela M.H., Kandawasvika G., Pediatric Surgery, Pediatrics, University of Zurich, National Institute of Health and Medical Research, Wellcome Trust, Medical Research Foundation, Shah, Priyen [0000-0001-9164-8862], Ulloa-Gutierrez, Rolando [0000-0002-9157-9227], Herberg, Jethro A [0000-0001-6941-6491], Cunnington, Aubrey J [0000-0002-1305-3529], Levin, Michael [0000-0003-2767-6919], and Apollo - University of Cambridge Repository

Subjects
Inotrope, Male, medicine.medical_treatment, 2700 General Medicine, 030204 cardiovascular system & hematology, Antibodies, Viral, Medical and Health Sciences, Cohort Studies, 0302 clinical medicine, Glucocorticoid, hemic and lymphatic diseases, Medicine and Health Sciences, 030212 general & internal medicine, Viral, Child, 11 Medical and Health Sciences, OUTCOMES, Respiration, Immunoglobulins, Intravenous, General Medicine, Systemic Inflammatory Response Syndrome, 3. Good health, Hospitalization, Treatment Outcome, Child, Preschool, Combination, Artificial, Regression Analysis, Drug Therapy, Combination, Female, Original Article, Intravenous, Life Sciences & Biomedicine, Cohort study, Human, medicine.medical_specialty, BATS Consortium, Adolescent, Immunoglobulins, 610 Medicine & health, Regression Analysi, Antibodies, Immunomodulation, 03 medical and health sciences, Medicine, General & Internal, Pharmacotherapy, Drug Therapy, Clinical Research, Internal medicine, General & Internal Medicine, medicine, MANAGEMENT, Confidence Intervals, Humans, Preschool, Propensity Score, Glucocorticoids, Mechanical ventilation, Science & Technology, business.industry, SARS-CoV-2, Inflammatory and immune system, COVID-19, Odds ratio, medicine.disease, Respiration, Artificial, Confidence interval, KAWASAKI-LIKE DISEASE, COVID-19 Drug Treatment, Systemic inflammatory response syndrome, 10036 Medical Clinic, Immunoglobulins, Intravenou, Propensity score matching, Cohort Studie, business, ACUTE RESPIRATORY SYNDROME, Confidence Interval, TOXIC-SHOCK-SYNDROME
Abstract

BackgroundEvidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.MethodsWe performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation.ResultsData were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups.ConclusionsWe found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).

Published
2021

5. SUCCOR Risk: Design and Validation of a Recurrence Prediction Index for Early-Stage Cervical Cancer

Author

Manzour, N., Chiva, L., Chacon, E., Martin-Calvo, N., Boria, F., Minguez, J. A., Alcazar, J. L., Zanagnolo, V., Querleu, D., Capilna, M., Fagotti, Anna, Kucukmetin, A., Mom, C., Chakalova, G., Aliyev, S., Malzoni, M., Narducci, F., Arencibia, O., Raspagliesi, F., Toptas, T., Cibula, D., Kaidarova, D., Meydanli, M., Tavares, M., Golub, D., Perrone, A., Poka, R., Tsolakidis, D., Vujic, G., Jedryka, M., Zusterzeel, P., Beltman, J., Goffin, F., Haidopoulos, D., Haller, H., Jach, R., Yezhova, I., Berlev, I., Bernardino, M., Bharathan, R., Lanner, M., Sukhin, V., Feron, J. G., Fruscio, R., Kukk, K., Ponce, J., Abdalla, N., Akbayir, O., Akgol, S., Aksahin, E., Alonso-Espias, M., Aluloski, I., Andrade, C., Badzakov, N., Barrachina, R., Bogani, G., Bonci, E. -A., Bonsang-Kitzis, H., Brucker, C., Cardenas, L., Casajuana, A., Cavalle, P., Cea, J., Chiofalo, B., Cordeiro, G., Coronado, P., Cuadra, M., Diez, J., da Costa, T. D., Domingo, S., Dostalek, L., Demirkiran, F., Erasun, D., Fehr, M., Fernandez-Gonzalez, S., Fidalgo, S., Fiol, G., Galaal, K., Garcia, J., Gebauer, G., Ghezzi, F., Gilabert, J., Gomes, N., Goncalves, E., Gonzalez, V., Grandjean, F., Guijarro, M., Guyon, F., Haesen, J., Hernandez-Cortes, G., Herrero, S., Pete, I., Kalogiannidis, I., Karaman, E., Kavallaris, A., Klasa, L., Kotsopoulos, I., Kovachev, S., Leht, M., Lekuona, A., Luyckx, M., Mallmann, M., Mancebo, G., Mandic, A., Marina, T., Martin, V., Martin-Salamanca, M. B., Martinez, A., Meili, G., Mendinhos, G., Mereu, L., Mitrovic, M., Morales, S., Moratalla, E., Morillas, B., Myriokefalitaki, E., Pakizimre, M., Petousis, S., Pirtea, L., Povolotskaya, N., Prader, S., Quesada, A., Redecha, M., Roldan, F., Rolland, P., Saaron, R., Sarac, C. -P., Scharf, J. -P., Smrkolj, S., Sousa, R., Stepanyan, A., Student, V., Tauste, C., Trum, H., Turan, T., Undurraga, M., Uppin, A., Vazquez, A., Vergote, I., Vorgias, G., Zapardiel, I., Fagotti A. (ORCID:0000-0001-5579-335X), Manzour, N., Chiva, L., Chacon, E., Martin-Calvo, N., Boria, F., Minguez, J. A., Alcazar, J. L., Zanagnolo, V., Querleu, D., Capilna, M., Fagotti, Anna, Kucukmetin, A., Mom, C., Chakalova, G., Aliyev, S., Malzoni, M., Narducci, F., Arencibia, O., Raspagliesi, F., Toptas, T., Cibula, D., Kaidarova, D., Meydanli, M., Tavares, M., Golub, D., Perrone, A., Poka, R., Tsolakidis, D., Vujic, G., Jedryka, M., Zusterzeel, P., Beltman, J., Goffin, F., Haidopoulos, D., Haller, H., Jach, R., Yezhova, I., Berlev, I., Bernardino, M., Bharathan, R., Lanner, M., Sukhin, V., Feron, J. G., Fruscio, R., Kukk, K., Ponce, J., Abdalla, N., Akbayir, O., Akgol, S., Aksahin, E., Alonso-Espias, M., Aluloski, I., Andrade, C., Badzakov, N., Barrachina, R., Bogani, G., Bonci, E. -A., Bonsang-Kitzis, H., Brucker, C., Cardenas, L., Casajuana, A., Cavalle, P., Cea, J., Chiofalo, B., Cordeiro, G., Coronado, P., Cuadra, M., Diez, J., da Costa, T. D., Domingo, S., Dostalek, L., Demirkiran, F., Erasun, D., Fehr, M., Fernandez-Gonzalez, S., Fidalgo, S., Fiol, G., Galaal, K., Garcia, J., Gebauer, G., Ghezzi, F., Gilabert, J., Gomes, N., Goncalves, E., Gonzalez, V., Grandjean, F., Guijarro, M., Guyon, F., Haesen, J., Hernandez-Cortes, G., Herrero, S., Pete, I., Kalogiannidis, I., Karaman, E., Kavallaris, A., Klasa, L., Kotsopoulos, I., Kovachev, S., Leht, M., Lekuona, A., Luyckx, M., Mallmann, M., Mancebo, G., Mandic, A., Marina, T., Martin, V., Martin-Salamanca, M. B., Martinez, A., Meili, G., Mendinhos, G., Mereu, L., Mitrovic, M., Morales, S., Moratalla, E., Morillas, B., Myriokefalitaki, E., Pakizimre, M., Petousis, S., Pirtea, L., Povolotskaya, N., Prader, S., Quesada, A., Redecha, M., Roldan, F., Rolland, P., Saaron, R., Sarac, C. -P., Scharf, J. -P., Smrkolj, S., Sousa, R., Stepanyan, A., Student, V., Tauste, C., Trum, H., Turan, T., Undurraga, M., Uppin, A., Vazquez, A., Vergote, I., Vorgias, G., Zapardiel, I., and Fagotti A. (ORCID:0000-0001-5579-335X)

Abstract

Objective: Based on the SUCCOR study database, our primary objective was to identify the independent clinical pathological variables associated with the risk of relapse in patients with stage IB1 cervical cancer who underwent a radical hysterectomy. Our secondary goal was to design and validate a risk predictive index (RPI) for classifying patients depending on the risk of recurrence. Methods: Overall, 1116 women were included from January 2013 to December 2014. We randomly divided our sample into two cohorts: discovery and validation cohorts. The test group was used to identify the independent variables associated with relapse, and with these variables, we designed our RPI. The index was applied to calculate a relapse risk score for each participant in the validation group. Results: A previous cone biopsy was the most significant independent variable that lowered the rate of relapse (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.17–0.60). Additionally, patients with a tumor diameter >2 cm on preoperative imaging assessment (OR 2.15, 95% CI 1.33–3.5) and operated by the minimally invasive approach (OR 1.61, 95% CI 1.00–2.57) were more likely to have a recurrence. Based on these findings, patients in the validation cohort were classified according to the RPI of low, medium, or high risk of relapse, with rates of 3.4%, 9.8%, and 21.3% observed in each group, respectively. With a median follow-up of 58 months, the 5-year disease-free survival rates were 97.2% for the low-risk group, 88.0% for the medium-risk group, and 80.5% for the high-risk group (p < 0.001). Conclusion: Previous conization to radical hysterectomy was the most powerful protective variable of relapse. Our risk predictor index was validated to identify patients at risk of recurrence.

Published
2022

6. SUCCOR cone study

Author

Chacon, E, Manzour, N, Zanagnolo, V, Querleu, D, Núñez-Córdoba, Jm, Martin-Calvo, N, Căpîlna, Me, Fagotti, A, Kucukmetin, A, Mom, C, Chakalova, G, Shamistan, A, Gil Moreno, A, Malzoni, M, Narducci, F, Arencibia, O, Raspagliesi, F, Toptas, T, Cibula, D, Kaidarova, D, Meydanli, Mm, Tavares, M, Golub, D, Perrone, Am, Poka, R, Tsolakidis, D, Vujić, G, Jedryka, Ma, Zusterzeel, Plm, Beltman, Jj, Goffin, F, Haidopoulos, D, Haller, H, Jach, R, Yezhova, I, Berlev, I, Bernardino, M, Bharathan, R, Lanner, M, Maenpaa, Mm, Sukhin, V, Feron, Jg, Fruscio, R, Kukk, K, Ponce, J, Minguez, Ja, Vázquez-Vicente, D, Castellanos, T, Boria, F, Alcazar, Jl, Chiva, L, SUCCOR study group, SUCCOR study Group: Abdalla, N, Akgöl, S, Aksahin, D, Aliyev, S, Alonso-Espias, M, Aluloski, I, Andrade, C, Badzakov, N, Barrachina, R, Bogani, G, Bonci, E-A, Bonsang-Kitzis, H, Brucker, C, Cárdenas, L, Casajuana, A, Cavalle, P, Cea, J, Chiofalo, B, Cordeiro, G, Coronado, P, Cuadra, M, Díez, J, Diniz da Costa, T, Domingo, S, Dostalek, L, Elif, F, Erasun, D, Fehr, M, Fernandez-Gonzalez, S, Ferrero, A, Fidalgo, S, Fiol, G, Galaal, K, García, J, Gebauer, G, Ghezzi, F, Gilabert, J, Gomes, N, Gonçalves, E, Gonzalez, V, Grandjean, F, Guijarro, M, Guyon, F, Haesen, J, Hernandez-Cortes, G, Herrero, S, Pete, I, Kalogiannidis, I, Karaman, E, Kavallaris, A, Klasa, L, Kotsopoulos, I, Stefan Kovachev, S, U A, Leht, Lekuona, A, Luyckx, M, Mallmann, M, Mancebo, G, Mandic, A, Marina, T, Martin, V, M B, Martín-Salamanca, Lago, V, Martinez, A, Meili, G, Mendinhos, G, Mereu, L, Mitrovic, M, Morales, S, Moratalla, E, N R, Gómez-Hidalgo, Morillas, B, Myriokefalitaki, E, Pakižimre, M, Petousis, S, Pirtea, L, Povolotskaya, N, Prader, S, Quesada, A, Redecha, M, Roldan, F, Rolland, P, Saaron, R, Sarac, C-P, Scharf, J-P, Smrkolj, S, Sousa, R, Stepanyan, A, Študent, V, Tauste, C, Trum, H, Turan, T, Undurraga, M, Vázquez, A, Vergote, I, Vorgias, G, and Zapardiel, I, Obstetrics and gynaecology, CCA - Cancer Treatment and quality of life, Amsterdam Reproduction & Development (AR&D), Chacon, E, Manzour, N, Zanagnolo, V, Querleu, D, Núñez-Córdoba, J, Martin-Calvo, N, Căpîlna, M, Fagotti, A, Kucukmetin, A, Mom, C, Chakalova, G, Shamistan, A, Gil Moreno, A, Malzoni, M, Narducci, F, Arencibia, O, Raspagliesi, F, Toptas, T, Cibula, D, Kaidarova, D, Meydanli, M, Tavares, M, Golub, D, Perrone, A, Poka, R, Tsolakidis, D, Vujić, G, Jedryka, M, Zusterzeel, P, Beltman, J, Goffin, F, Haidopoulos, D, Haller, H, Jach, R, Yezhova, I, Berlev, I, Bernardino, M, Bharathan, R, Lanner, M, Maenpaa, M, Sukhin, V, Feron, J, Fruscio, R, Kukk, K, Ponce, J, Minguez, J, Vázquez-Vicente, D, Castellanos, T, Boria, F, Alcazar, J, and Chiva, L

Subjects
Adult, Databases, Factual, cervical cancer, Conization, Obstetrics and Gynecology, Uterine Cervical Neoplasms, Middle Aged, Disease-Free Survival, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], surgery, Settore MED/40 - GINECOLOGIA E OSTETRICIA, laparoscopes, laparoscope, Oncology, laparotomy, Humans, Minimally Invasive Surgical Procedures, Female, Neoplasm Recurrence, Local, hysterectomy, Propensity Score, Retrospective Studies
Abstract

ObjectiveTo evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009).MethodsA multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score.ResultsWe obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively).ConclusionsIn this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

Published
2022
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7. Treatment of Multisystem Inflammatory Syndrome in Children

Author

McArdle, A.J. Vito, O. Patel, H. Seaby, E.G. Shah, P. Wilson, C. Broderick, C. Nijman, R. Tremoulet, A.H. Munblit, D. Ulloa-Gutierrez, R. Carter, M.J. De, T. Hoggart, C. Whittaker, E. Herberg, J.A. Kaforou, M. Cunnington, A.J. Levin, M. Vazquez, J.A. Carmona, R. Perez, L. Rubinos, M. Veliz, N. Yori, S. Haerynck, F. Hoste, L. Leal, I.A. Da Silva, A.R.A. Silva, A.E.A. Barchik, A. Barreiro, S.T.A. Cochrane, N. Teixeira, C.H. Arauj, J.M. Ossa, R.A.P.-D.L. Vieira, C.S. Dimitrova, A. Ganeva, M. Stefanov, S. Telcharova-Mihaylovska, A. Biggs, C.M. Scuccimarri, R. Withington, D. Raul, B.B. Ampuero, C. Aravena, J. Casanova, D. Cruces, P. Diaz, F. Garcia-Salum, T. Godoy, L. Medina, R.A. Galaz, G.V. Avila-Aguero, M.L. Brenes-Chacon, H. Ivankovich-Escoto, G. Yock-Corrales, A. Badib, A. Badreldin, K. Elkhashab, Y. Heshmat, H. Heinonen, S. Angoulvant, F. Belot, A. Ouldali, N. Beske, F. Heep, A. Masjosthusmann, K. Reiter, K. Heuvel, I.V.D. Both, U.V. Agrafiotou, A. Antachopoulos, C. Eleftheriou, I. Farmaki, E. Fotis, L. Kafetzis, D. Lampidi, S. Liakopoulou, T. Maritsi, D. Michailidou, E. Milioudi, M. Mparmpounaki, I. Papadimitriou, E. Papaevangelou, V. Roilides, E. Tsiatsiou, O. Tsolas, G. Tsolia, M. Vantsi, P. Pineda, L.Y.B. Aguilar, K.L.B. Quintero, E.M.C. Ip, P. Kwan, M.Y.W. Kwok, J. Lau, Y.L. To, K. Wong, J.S.C. David, M. Farkas, D. Kalcakosz, S. Szekeres, K. Zsigmond, B. Aslam, N. Andreozzi, L. Bianco, F. Bucciarelli, V. Buonsenso, D. Cimaz, R. D'Argenio, P. Dellepiane, R.M. Fabi, M. Mastrolia, M.V. Mauro, A. Mazza, A. Romani, L. Simonini, G. Tipo, V. Valentini, P. Verdoni, L. Reel, B. Pace, D. Torpiano, P. Flores, M.F. Domínguez, M.G. Vargas, A.L.G. Hernandez, L.L. Figueroa, R.P.M. Gaxiola, G.P. Valadez, J. Klevberg, S. Knudsen, P.K. Maseide, P.H. Carrera, J.M. Castano, E.G. Timana, C.A.D. Leon, T.D. Estripeaut, D. Levy, J. Norero, X. Record, J. Rojas-Bonilla, M. Iramain, R. Hernandez, R. Huaman, G. Munaico, M. Peralta, C. Seminario, D. Yarleque, E.H.Z. Gadzinska, J. Mandziuk, J. Okarska-Napierała, M. Alacheva, Z.A. Alexeeva, E. Ananin, P.V. Antsupova, M. Bakradze, M.D. Bobkova, P. Borzakova, S. Chashchina, I.L. Fisenko, A.P. Gautier, M.S. Glazyrina, A. Kondrikova, E. Korobyants, E. Korsunskiy, A.A. Kovygina, K. Krasnaya, E. Kurbanova, S. Kurdup, M.K. Mamutova, A.V. Mazankova, L. Mitushin, I.L. Nargizyan, A. Orlova, Y.O. Osmanov, I.M. Polyakova, A.S. Romanova, O. Samitova, E. Sologub, A. Spiridonova, E. Tepaev, R.F. Tkacheva, A.A. Yusupova, V. Zholobova, E. Grasa, C.D. Segura, N.L. Martinon-Torres, F. Melendo, S. Echevarria, A.M. Guzman, J.M.M. Argueta, J.R.P. Rivero-Calle, I. Riviere, J. Rodriguez-Gonzalez, M. Rojo, P. Manubens, J.S. Soler-Palacin, P. Soriano-Arandes, A. Tagarro, A. Villaverde, S. Altman, M. Brodin, P. Horne, A. Palmblad, K. Brotschi, B. Sauteur, P.M. Schmid, J.P. Prader, S. Relly, C. Schlapbach, L.J. Seiler, M. Truck, J. Wutz, D. Ketharanathan, N. Vermont, C. Ozkan, E.A. Erdeniz, E.H. Borisova, G. Boychenko, L. Diudenko, N. Kasiyan, O. Katerynych, K. Melnyk, K. Miagka, N. Teslenko, M. Trykosh, M. Volokha, A. Akomolafe, T. Al-Abadi, E. Alders, N. Avram, P. Bamford, A. Bank, M. Roy, R.B. Beattie, T. Boleti, O. Broad, J. Carrol, E.D. Chandran, A. Cooper, H. Davies, P. Emonts, M. Evans, C. Fidler, K. Foster, C. Gong, C. Gongrun, B. Gonzalez, C. Grandjean, L. Grant, K. Hacohen, Y. Hall, J. Hassell, J. Hesketh, C. Hewlett, J. Hnieno, A. Holt-Davis, H. Hossain, A. Hudson, L.D. Johnson, M. Johnson, S. Jyothish, D. Kampmann, B. Kavirayani, A. Kelly, D. Kucera, F. Langer, D. Lillie, J. Longbottom, K. Lyall, H. MacKdermott, N. Maltby, S. McLelland, T. McMahon, A.-M. Miller, D. Morrison, Z. Mosha, K. Muller, J. Myttaraki, E. Nadel, S. Osaghae, D. Osman, F. Ostrzewska, A. Panthula, M. Papachatzi, E. Papadopoulou, C. Penner, J. Polandi, S. Prendergast, A.J. Ramnarayan, P. Rhys-Evans, S. Riordan, A. Rodrigues, C.M.C. Romaine, S. Seddon, J. Shingadia, D. Srivastava, A. Struik, S. Taylor, A. Taylor, A. Taylor, A. Tran, S. Tudor-Williams, G. Van Der Velden, F. Ventilacion, L. Wellman, P.A. Yanney, M.P. Yeung, S. Badheka, A. Badran, S. Bailey, D.M. Burch, A.K. Burns, J.C. Cichon, C. Cirks, B. Dallman, M.D. Delany, D.R. Fairchok, M. Friedman, S. Geracht, J. Langs-Barlow, A. Mann, K. Padhye, A. Quade, A. Ramirez, K.A. Rockett, J. Sayed, I.A. Shahin, A.A. Umaru, S. Widener, R. Angela, M.H. Kandawasvika, G. BATS Consortium

Subjects
hemic and lymphatic diseases
Abstract

BACKGROUND Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2. METHODS We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation. RESULTS Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups. CONCLUSIONS We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. Copyright © 2021 Massachusetts Medical Society.

Published
2021

8. Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia

Author

Zielen, S., Duecker, R.P., Woelke, S., Donath, H., Bakhtiar, S., Buecker, A., Kreyenberg, H., Huenecke, S., Bader, P., Mahlaoui, N., Ehl, S., El-Helou, S.M., Pietrucha, B., Plebani, A., Flier, M. van der, Aerde, K.J. van, Kilic, S.S., Reda, S.M., Kostyuchenko, L., McDermott, E., Galal, N., Pignata, C., Pérez, J.L.S., Laws, H.J., Niehues, T., Kutukculer, N., Seidel, M.G., Marques, L., Ciznar, P., Edgar, J.D.M., Soler-Palacín, P., Bernuth, H. von, Krueger, R., Meyts, I., Baumann, U., Kanariou, M., Grimbacher, B., Hauck, F., Graf, D., Granado, L.I.G., Prader, S., Reisli, I., Slatter, M., Rodríguez-Gallego, C., Arkwright, P.D., Bethune, C., Deripapa, E., Sharapova, S.O., Lehmberg, K., Davies, E.G., Schuetz, C., Kindle, G., Schubert, R., Zielen, S., Duecker, R.P., Woelke, S., Donath, H., Bakhtiar, S., Buecker, A., Kreyenberg, H., Huenecke, S., Bader, P., Mahlaoui, N., Ehl, S., El-Helou, S.M., Pietrucha, B., Plebani, A., Flier, M. van der, Aerde, K.J. van, Kilic, S.S., Reda, S.M., Kostyuchenko, L., McDermott, E., Galal, N., Pignata, C., Pérez, J.L.S., Laws, H.J., Niehues, T., Kutukculer, N., Seidel, M.G., Marques, L., Ciznar, P., Edgar, J.D.M., Soler-Palacín, P., Bernuth, H. von, Krueger, R., Meyts, I., Baumann, U., Kanariou, M., Grimbacher, B., Hauck, F., Graf, D., Granado, L.I.G., Prader, S., Reisli, I., Slatter, M., Rodríguez-Gallego, C., Arkwright, P.D., Bethune, C., Deripapa, E., Sharapova, S.O., Lehmberg, K., Davies, E.G., Schuetz, C., Kindle, G., and Schubert, R.

Abstract

Item does not contain fulltext, Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA deficiency collected from the European Society for Immunodeficiencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe-University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (n = 31) due to a further decrease of naïve CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-ß repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials.gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978).

Published
2021

9. X-Linked Lymphoproliferative Disease Mimicking Multisystem Inflammatory Syndrome in Children-A Case Report

Author

Prader, S, Ritz, N, Baleydier, F, Andre, MC, Staehli, N, Schmid, K, Schmid, H, Woerner, A, Diesch, T, Sauteur, PMM, Trueck, J, Gebistorf, F, Opitz, L, Killian, MP, Marchetti, T, Vavassori, S, Blanchard-Rohner, G, Mc Lin, V, Grazioli, S, Schmid, JP, Prader, S, Ritz, N, Baleydier, F, Andre, MC, Staehli, N, Schmid, K, Schmid, H, Woerner, A, Diesch, T, Sauteur, PMM, Trueck, J, Gebistorf, F, Opitz, L, Killian, MP, Marchetti, T, Vavassori, S, Blanchard-Rohner, G, Mc Lin, V, Grazioli, S, and Schmid, JP

Abstract

Most children with a SARS-CoV-2 infection are asymptomatic or exhibit mild symptoms. However, a small number of children develop features of substantial inflammation temporarily related to the COVID-19 also called multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), clinically similar to Kawasaki disease, toxic shock syndrome and hemophagocytic lymphohistiocytosis (HLH). It is well-known that genetic pre-disposition plays an important role in virally-triggered diseases such as Epstein-Barr virus (EBV)-associated HLH, while this has not yet been established for patients with MIS-C. Here we describe a male patient fulfilling the diagnostic criteria of MIS-C, who was initially treated according to current consensus guidelines. Presence of hypofibrinogenemia, normal lymphocyte counts and C-reactive protein, but substantial hyperferritinemia distinguish this patient from others with MIS-C. The clinical course following initial presentation with acute respiratory distress syndrome was marked by fatal liver failure in the context of EBV-associated HLH despite treatment with steroids, intravenous immunoglobulins, interleukin (IL)-1 receptor blockade and eventually HLH-directed treatment. X-linked lymphoproliferative disease type 1 (XLP1), a subtype of primary HLH was diagnosed in this patient post-mortem. This case report highlights the importance of including HLH in the differential diagnosis in MIS-C with severe disease course to allow specific, risk-adapted treatment and genetic counseling.

Published
2021

10. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Author

De Placido, S, Gallo, C, De Laurentiis, M, Bisagni, G, Arpino, G, Sarobba, M, Riccardi, F, Russo, A, Del Mastro, L, Cogoni, A, Cognetti, F, Gori, S, Foglietta, J, Frassoldati, A, Amoroso, D, Laudadio, L, Moscetti, L, Montemurro, F, Verusio, C, Bernardo, A, Lorusso, V, Gravina, A, Moretti, G, Lauria, R, Lai, A, Mocerino, C, Rizzo, S, Nuzzo, F, Carlini, P, Perrone, F, Accurso, A, Agostara, B, Aieta, M, Alabiso, O, Alicicco, M, Amadori, D, Amaducci, L, Amiconi, G, Antuzzi, G, Ardine, M, Ardizzoia, A, Aversa, C, Badalamenti, G, Barni, S, Basurto, C, Berardi, R, Bergamasco, C, Bidoli, P, Bighin, C, Biondi, E, Boni, C, Borgonovo, K, Botta, M, Bravi, S, Bruzzi, P, Buono, G, Butera, A, Caldara, A, Candeloro, G, Cappelletti, C, Cardalesi, C, Carfora, E, Cariello, A, Carrozza, F, Carteni, G, Caruso, M, Casadei, V, Casanova, C, Castori, L, Cavanna, L, Cavazzini, G, Cazzaniga, M, Chilelli, M, Chiodini, P, Chiorrini, S, Ciardiello, F, Ciccarese, M, Cinieri, S, Clerico, M, Coccaro, M, Comande, M, Corbo, C, Cortino, G, Cusenza, S, Daniele, G, D'Arco, A, D'Auria, G, Dazzi, C, De Angelis, C, de Braud, F, De Feo, G, De Matteis, A, De Tursi, M, Di Blasio, A, di Lucca, G, Di Lullo, L, Di Rella, F, Di Renzo, G, Di Stefano, P, Di Stefano, A, Diana, A, Donati, S, Fabbri, A, Fabi, A, Faedi, M, Farina, G, Farris, A, Febbraro, A, Fedele, P, Federico, P, Ferrau, F, Ferretti, G, Ferro, A, Floriani, I, Forcignano, R, Forciniti, S, Forestieri, V, Fornari, G, Frisinghelli, M, Fusco, V, Gallizzi, G, Galvano, A, Gambardella, A, Gambi, A, Gebbia, V, Gervasi, E, Ghilardi, M, Giacobino, A, Giardina, G, Giotta, F, Giraudi, S, Giuliano, M, Grassadonia, A, Grasso, D, Grosso, F, Guizzaro, L, Incoronato, P, Incorvaia, L, Iodice, G, La Verde, N, Labonia, V, Landi, G, Latorre, A, Leonardi, V, Levaggi, A, Limite, G, Lina Bascialla, L, Livi, L, Maiello, E, Mandelli, D, Marcon, I, Menon, D, Montedoro, M, Moraca, L, Moretti, A, Morritti, M, Morselli, P, Mura, A, Mura, S, Musacchio, M, Muzio, A, Natale, D, Natoli, C, Nigro, C, Nistico, C, Nuzzo, A, Orditura, M, Orlando, L, Pacilio, C, Palumbo, G, Palumbo, R, Pasini, F, Paterno, E, Pazzola, A, Pelliccioni, S, Pensabene, M, Perroni, D, Pesenti Gritti, A, Petrelli, F, Piccirillo, M, Pinotti, G, Pogliani, C, Poli, D, Prader, S, Recchia, F, Rizzi, D, Romano, C, Rossello, R, Rossini, C, Salvucci, G, Sanna, V, Santini, A, Saracchini, S, Savastano, C, Scambia, G, Schettini, F, Schiavone, P, Schirone, A, Seles, E, Signoriello, S, Signoriello, G, Silva, R, Silvestri, A, Simeon, V, Spagnoletti, I, Tamberi, S, Teragni, C, Thalmann, V, Thomas, R, Thomas, G, Tienghi, A, Tinari, N, Tinessa, V, Tomei, F, Tonini, G, Torri, V, Traficante, D, Tudini, M, Turazza, M, Vignoli, R, Vitale, M, Zacchia, A, Zagarese, P, Zanni, A, Zavallone, L, Zavettieri, M, Zoboli, A, De Placido S., Gallo C., De Laurentiis M., Bisagni G., Arpino G., Sarobba M. G., Riccardi F., Russo A., Del Mastro L., Cogoni A. A., Cognetti F., Gori S., Foglietta J., Frassoldati A., Amoroso D., Laudadio L., Moscetti L., Montemurro F., Verusio C., Bernardo A., Lorusso V., Gravina A., Moretti G., Lauria R., Lai A., Mocerino C., Rizzo S., Nuzzo F., Carlini P., Perrone F., Accurso A., Agostara B., Aieta M., Alabiso O., Alicicco M. G., Amadori D., Amaducci L., Amiconi G., Antuzzi G., Ardine M., Ardizzoia A., Aversa C., Badalamenti G., Barni S., Basurto C., Berardi R., Bergamasco C., Bidoli P., Bighin C., Biondi E., Boni C., Borgonovo K., Botta M., Bravi S., Bruzzi P., Buono G., Butera A., Caldara A., Candeloro G., Cappelletti C., Cardalesi C., Carfora E., Cariello A., Carrozza F., Carteni G., Caruso M., Casadei V., Casanova C., Castori L., Cavanna L., Cavazzini G., Cazzaniga M., Chilelli M., Chiodini P., Chiorrini S., Ciardiello F., Ciccarese M., Cinieri S., Clerico M., Coccaro M., Comande M., Corbo C., Cortino G., Cusenza S., Daniele G., D'arco A. M., D'auria G., Dazzi C., De Angelis C., de Braud F., De Feo G., De Matteis A., De Tursi M., Di Blasio A., di Lucca G., Di Lullo L., Di Rella F., Di Renzo G., Di Stefano P., Di Stefano A., Diana A., Donati S., Fabbri A., Fabi A., Faedi M., Farina G., Farris A., Febbraro A., Fedele P., Federico P., Ferrau F., Ferretti G., Ferro A., Floriani I., Forcignano R., Forciniti S., Forestieri V., Fornari G., Frisinghelli M., Fusco V., Gallizzi G., Galvano A., Gambardella A., Gambi A., Gebbia V., Gervasi E., Ghilardi M., Giacobino A., Giardina G., Giotta F., Giraudi S., Giuliano M., Grassadonia A., Grasso D., Grosso F., Guizzaro L., Incoronato P., Incorvaia L., Iodice G., La Verde N., Labonia V., Landi G., Latorre A., Leonardi V., Levaggi A., Limite G., Lina Bascialla L., Livi L., Maiello E., Mandelli D., Marcon I., Menon D., Montedoro M., Moraca L., Moretti A., Morritti M. G., Morselli P., Mura A., Mura S., Musacchio M., Muzio A., Natale D., Natoli C., Nigro C., Nistico C., Nuzzo A., Orditura M., Orlando L., Pacilio C., Palumbo G., Palumbo R., Pasini F., Paterno E., Pazzola A., Pelliccioni S., Pensabene M., Perroni D., Pesenti Gritti A., Petrelli F., Piccirillo M. C., Pinotti G., Pogliani C., Poli D., Prader S., Recchia F., Rizzi D., Romano C., Rossello R., Rossini C., Salvucci G., Sanna V., Santini A., Saracchini S., Savastano C., Scambia G., Schettini F., Schiavone P., Schirone A., Seles E., Signoriello S., Signoriello G., Silva R. R., Silvestri A., Simeon V., Spagnoletti I., Tamberi S., Teragni C., Thalmann V., Thomas R., Thomas G., Tienghi A., Tinari N., Tinessa V., Tomei F., Tonini G., Torri V., Traficante D., Tudini M., Turazza M., Vignoli R., Vitale M. G., Zacchia A., Zagarese P., Zanni A., Zavallone L., Zavettieri M., Zoboli A., De Placido, S, Gallo, C, De Laurentiis, M, Bisagni, G, Arpino, G, Sarobba, M, Riccardi, F, Russo, A, Del Mastro, L, Cogoni, A, Cognetti, F, Gori, S, Foglietta, J, Frassoldati, A, Amoroso, D, Laudadio, L, Moscetti, L, Montemurro, F, Verusio, C, Bernardo, A, Lorusso, V, Gravina, A, Moretti, G, Lauria, R, Lai, A, Mocerino, C, Rizzo, S, Nuzzo, F, Carlini, P, Perrone, F, Accurso, A, Agostara, B, Aieta, M, Alabiso, O, Alicicco, M, Amadori, D, Amaducci, L, Amiconi, G, Antuzzi, G, Ardine, M, Ardizzoia, A, Aversa, C, Badalamenti, G, Barni, S, Basurto, C, Berardi, R, Bergamasco, C, Bidoli, P, Bighin, C, Biondi, E, Boni, C, Borgonovo, K, Botta, M, Bravi, S, Bruzzi, P, Buono, G, Butera, A, Caldara, A, Candeloro, G, Cappelletti, C, Cardalesi, C, Carfora, E, Cariello, A, Carrozza, F, Carteni, G, Caruso, M, Casadei, V, Casanova, C, Castori, L, Cavanna, L, Cavazzini, G, Cazzaniga, M, Chilelli, M, Chiodini, P, Chiorrini, S, Ciardiello, F, Ciccarese, M, Cinieri, S, Clerico, M, Coccaro, M, Comande, M, Corbo, C, Cortino, G, Cusenza, S, Daniele, G, D'Arco, A, D'Auria, G, Dazzi, C, De Angelis, C, de Braud, F, De Feo, G, De Matteis, A, De Tursi, M, Di Blasio, A, di Lucca, G, Di Lullo, L, Di Rella, F, Di Renzo, G, Di Stefano, P, Di Stefano, A, Diana, A, Donati, S, Fabbri, A, Fabi, A, Faedi, M, Farina, G, Farris, A, Febbraro, A, Fedele, P, Federico, P, Ferrau, F, Ferretti, G, Ferro, A, Floriani, I, Forcignano, R, Forciniti, S, Forestieri, V, Fornari, G, Frisinghelli, M, Fusco, V, Gallizzi, G, Galvano, A, Gambardella, A, Gambi, A, Gebbia, V, Gervasi, E, Ghilardi, M, Giacobino, A, Giardina, G, Giotta, F, Giraudi, S, Giuliano, M, Grassadonia, A, Grasso, D, Grosso, F, Guizzaro, L, Incoronato, P, Incorvaia, L, Iodice, G, La Verde, N, Labonia, V, Landi, G, Latorre, A, Leonardi, V, Levaggi, A, Limite, G, Lina Bascialla, L, Livi, L, Maiello, E, Mandelli, D, Marcon, I, Menon, D, Montedoro, M, Moraca, L, Moretti, A, Morritti, M, Morselli, P, Mura, A, Mura, S, Musacchio, M, Muzio, A, Natale, D, Natoli, C, Nigro, C, Nistico, C, Nuzzo, A, Orditura, M, Orlando, L, Pacilio, C, Palumbo, G, Palumbo, R, Pasini, F, Paterno, E, Pazzola, A, Pelliccioni, S, Pensabene, M, Perroni, D, Pesenti Gritti, A, Petrelli, F, Piccirillo, M, Pinotti, G, Pogliani, C, Poli, D, Prader, S, Recchia, F, Rizzi, D, Romano, C, Rossello, R, Rossini, C, Salvucci, G, Sanna, V, Santini, A, Saracchini, S, Savastano, C, Scambia, G, Schettini, F, Schiavone, P, Schirone, A, Seles, E, Signoriello, S, Signoriello, G, Silva, R, Silvestri, A, Simeon, V, Spagnoletti, I, Tamberi, S, Teragni, C, Thalmann, V, Thomas, R, Thomas, G, Tienghi, A, Tinari, N, Tinessa, V, Tomei, F, Tonini, G, Torri, V, Traficante, D, Tudini, M, Turazza, M, Vignoli, R, Vitale, M, Zacchia, A, Zagarese, P, Zanni, A, Zavallone, L, Zavettieri, M, Zoboli, A, De Placido S., Gallo C., De Laurentiis M., Bisagni G., Arpino G., Sarobba M. G., Riccardi F., Russo A., Del Mastro L., Cogoni A. A., Cognetti F., Gori S., Foglietta J., Frassoldati A., Amoroso D., Laudadio L., Moscetti L., Montemurro F., Verusio C., Bernardo A., Lorusso V., Gravina A., Moretti G., Lauria R., Lai A., Mocerino C., Rizzo S., Nuzzo F., Carlini P., Perrone F., Accurso A., Agostara B., Aieta M., Alabiso O., Alicicco M. G., Amadori D., Amaducci L., Amiconi G., Antuzzi G., Ardine M., Ardizzoia A., Aversa C., Badalamenti G., Barni S., Basurto C., Berardi R., Bergamasco C., Bidoli P., Bighin C., Biondi E., Boni C., Borgonovo K., Botta M., Bravi S., Bruzzi P., Buono G., Butera A., Caldara A., Candeloro G., Cappelletti C., Cardalesi C., Carfora E., Cariello A., Carrozza F., Carteni G., Caruso M., Casadei V., Casanova C., Castori L., Cavanna L., Cavazzini G., Cazzaniga M., Chilelli M., Chiodini P., Chiorrini S., Ciardiello F., Ciccarese M., Cinieri S., Clerico M., Coccaro M., Comande M., Corbo C., Cortino G., Cusenza S., Daniele G., D'arco A. M., D'auria G., Dazzi C., De Angelis C., de Braud F., De Feo G., De Matteis A., De Tursi M., Di Blasio A., di Lucca G., Di Lullo L., Di Rella F., Di Renzo G., Di Stefano P., Di Stefano A., Diana A., Donati S., Fabbri A., Fabi A., Faedi M., Farina G., Farris A., Febbraro A., Fedele P., Federico P., Ferrau F., Ferretti G., Ferro A., Floriani I., Forcignano R., Forciniti S., Forestieri V., Fornari G., Frisinghelli M., Fusco V., Gallizzi G., Galvano A., Gambardella A., Gambi A., Gebbia V., Gervasi E., Ghilardi M., Giacobino A., Giardina G., Giotta F., Giraudi S., Giuliano M., Grassadonia A., Grasso D., Grosso F., Guizzaro L., Incoronato P., Incorvaia L., Iodice G., La Verde N., Labonia V., Landi G., Latorre A., Leonardi V., Levaggi A., Limite G., Lina Bascialla L., Livi L., Maiello E., Mandelli D., Marcon I., Menon D., Montedoro M., Moraca L., Moretti A., Morritti M. G., Morselli P., Mura A., Mura S., Musacchio M., Muzio A., Natale D., Natoli C., Nigro C., Nistico C., Nuzzo A., Orditura M., Orlando L., Pacilio C., Palumbo G., Palumbo R., Pasini F., Paterno E., Pazzola A., Pelliccioni S., Pensabene M., Perroni D., Pesenti Gritti A., Petrelli F., Piccirillo M. C., Pinotti G., Pogliani C., Poli D., Prader S., Recchia F., Rizzi D., Romano C., Rossello R., Rossini C., Salvucci G., Sanna V., Santini A., Saracchini S., Savastano C., Scambia G., Schettini F., Schiavone P., Schirone A., Seles E., Signoriello S., Signoriello G., Silva R. R., Silvestri A., Simeon V., Spagnoletti I., Tamberi S., Teragni C., Thalmann V., Thomas R., Thomas G., Tienghi A., Tinari N., Tinessa V., Tomei F., Tonini G., Torri V., Traficante D., Tudini M., Turazza M., Vignoli R., Vitale M. G., Zacchia A., Zagarese P., Zanni A., Zavallone L., Zavettieri M., and Zoboli A.

Abstract

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is regist

Published
2018

11. Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis

Author

Felber, M., Steward, C.G., Kentouche, K., Fasth, A., Wynn, R.F., Zeilhofer, U., Haunerdinger, V., Volkmer, B., Prader, S., Gruhn, B., Ehl, S., Lehmberg, K., Muller, D., Gennery, A.R., Albert, M.H., Hauck, F., Rao, K., Veys, P., Hassan, M., Lankester, A.C., Schmid, J.P., Hauri-Hohl, M.M., Gungor, T., Inborn Errors Working Party IEWP E, European Soc Immunodeficiencies ES, and University of Zurich

Subjects
medicine.medical_specialty, Hemophagocytic lymphohistiocytosis, business.industry, medicine.medical_treatment, 2720 Hematology, 610 Medicine & health, Hematology, Hematopoietic stem cell transplantation, Defibrotide, medicine.disease, Gastroenterology, Fludarabine, medicine.anatomical_structure, 10036 Medical Clinic, Cord blood, Internal medicine, 540 Chemistry, Medicine, Alemtuzumab, Bone marrow, business, Busulfan, 10038 Institute of Clinical Chemistry, medicine.drug
Abstract

Reduced-intensity/reduced-toxicity conditioning and allogeneic T-cell replete hematopoietic stem cell transplantation are curative in patients with hemophagocytic lymphohistiocytosis (HLH). Unstable donor chimerism (DC) and relapses are clinical challenges . We examined the effect of a reduced-intensity conditioning regimen based on targeted busulfan to enhance myeloid DC in HLH. The European Society for Bone and Marrow Transplantation–approved reduced-intensity conditioning protocol comprised targeted submyeloablative IV busulfan, IV fludarabine, and serotherapy comprising IV alemtuzumab (0.5-0.8 mg/kg) for unrelated-donor and IV rabbit anti–T-cell globulin for related-donor transplants. We assessed toxicity, engraftment, graft-versus-host disease (GHVD), DC in blood cell subtypes, and overall survival/event-free survival. Twenty-five patients from 7 centers were treated (median age, 0.68 year). The median total dose and cumulative area under the curve of busulfan was 13.1 mg/kg (6.4-26.4) and 63.1 mg/L × h (48-77), respectively. Bone marrow, peripheral blood stem cell, or cord blood transplants from HLA-matched related (n = 7) or unrelated (n = 18) donors were administered. Donor cells engrafted in all patients (median: neutrophils d+20/platelets d+28). At last follow-up (median, 36 months; range, 8-111 months), the median DC of CD15+ neutrophils, CD3+ T cells, and CD16+56+ natural killer cells was 99.5% (10-100), 97% (30-100), and 97.5% (30-100), respectively. Eight patients (32%) developed sinusoidal obstruction syndrome, resolving after defibrotide treatment. The 3-year overall survival and event-free survival rates were both 100%. None of the patients developed acute grade III to IV GHVD. Limited chronic GVHD was encountered in 4%. This regimen achieves excellent results with stable DC in patients with HLH.

Published
2020

13. Dilution of molecular-pathologic gene signatures (MPG) by parameter unrelated to tumor biology (UTB) may prevent prediction of the resection status after debulking surgery in patients with advanced ovarian cancer : Oral Communication 3 – Ovarian Cancer

Author

Heitz, F., Kommoss, S., Tourani, R., Grandelis, A., Uppendahl, L., Aliferis, C., Burges, A., Wang, C., Canzler, U., Wang, J., Belau, A., Prader, S., Hanker, L., Ma, S., Ataseven, B., Hilpert, F., Schneider, S., Sehouli, J, Kimmig, Rainer, Kurzeder, C., Schmalfeldt, B., Braicu, I., Harter, P., Dowdy, S. C., Winterhoff, B. J. N., Pfisterer, J., and Bois, A. du

Subjects
Medizin
Published
2019

14. Disease evolution and response to rapamycin in Activated Phosphoinositide 3-Kinase delta syndrome: the european society for immunodeficiencies-Activated Phosphoinositide 3-Kinase d syndrome registry

Author

Maccari, M.E., Abolhassani, H., Aghamohammadi, A., Aiuti, A., Aleinikova, O., Bangs, C., Baris, S., Barzaghi, F., Baxendale, H., Buckland, M., Burns, S.O., Cancrini, C., Cant, A., Cathebras, P., Cavazzana, M., Chandra, A., Conti, F., Coulter, T., Devlin, L.A., Edgar, J.D.M., Faust, S., Fischer, A., Prat, M.G., Hammarstrom, L., Heeg, M., Jolles, S., Karakoc-Aydiner, E., Kindle, G., Kiykim, A., Kumararatne, D., Grimbacher, B., Longhurst, H., Mahlaoui, N., Milota, T., Moreira, F., Moshous, D., Mukhina, A., Neth, O., Neven, B., Nieters, A., Olbrich, P., Ozen, A., Schmid, J.P., Picard, C., Prader, S., Rae, W., Reichenbach, J., Rusch, S., Savic, S., Scarselli, A., Scheible, R., Sediva, A., Sharapova, S.O., Shcherbina, A., Slatter, M., Soler-Palacin, P., Stanislas, A., Suarez, F., Tucci, F., Uhlmann, A., van Montfrans, J., Warnatz, K., Williams, A.P., Wood, P., Kracker, S., Condliffe, A.M., and Ehl, S.

Abstract

Activated phosphoinositide 3-kinase (PI3K) δ Syndrome (APDS), caused by autosomal\ud dominant mutations in PIK3CD (APDS1) or PIK3R1 (APDS2), is a heterogeneous primary\ud immunodeficiency. While initial cohort-descriptions summarized the spectrum of clinical\ud and immunological manifestations, questions about long-term disease evolution and\ud response to therapy remain. The prospective European Society for Immunodeficiencies\ud (ESID)-APDS registry aims to characterize the disease course, identify outcome predictors,\ud and evaluate treatment responses. So far, 77 patients have been recruited (51\ud APDS1, 26 APDS2). Analysis of disease evolution in the first 68 patients pinpoints the early\ud occurrence of recurrent respiratory infections followed by chronic lymphoproliferation,\ud gastrointestinal manifestations, and cytopenias. Although most manifestations occur by\ud age 15, adult-onset and asymptomatic courses were documented. Bronchiectasis was\ud observed in 24/40 APDS1 patients who received a CT-scan compared with 4/15 APDS2\ud patients. By age 20, half of the patients had received at least one immunosuppressant,\ud but 2–3 lines of immunosuppressive therapy were not unusual before age 10. Response\ud to rapamycin was rated by physician visual analog scale as good in 10, moderate in 9,\ud and poor in 7. Lymphoproliferation showed the best response (8 complete, 11 partial,\ud 6 no remission), while bowel inflammation (3 complete, 3 partial, 9 no remission) and\ud cytopenia (3 complete, 2 partial, 9 no remission) responded less well. Hence, non-lymphoproliferative\ud manifestations should be a key target for novel therapies. This report from\ud the ESID-APDS registry provides comprehensive baseline documentation for a growing\ud cohort that will be followed prospectively to establish prognostic factors and identify\ud patients for treatment studies.

Published
2018

16. Liquid biopsy zur objektiven Beurteilung des post-operativen Tumorrestes bei Patientinnen mit fortgeschrittenem high-grade serösem Ovarialkarzinom

Author

Hengsbach, A, additional, Lakis, S, additional, Heitz, F, additional, Talwar, A, additional, Sehouli, J, additional, Bommert, M, additional, Bertrand, M, additional, Ataseven, B, additional, Müller, JN, additional, Schneider, S, additional, Mariotti, E, additional, Prader, S, additional, Menon, R, additional, Leenders, F, additional, Heukamp, LC, additional, Braicu, I, additional, Glöckner, C, additional, du Bois, A, additional, and Heuckmann, JM, additional

Published
2018
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17. Change of patient perceptions of chemotherapy side effects in breast and ovarian cancer patients

Author

Frindte, J, additional, Ataseven, B, additional, Harter, P, additional, Göke, G, additional, Podkowinkski, J, additional, Vogt, C, additional, Bluni, V, additional, Vincent, M, additional, Traut, A, additional, Heitz, F, additional, Kümmel, S, additional, Prader, S, additional, Bommert, M, additional, Schneider, S, additional, and du Bois, A, additional

Published
2018
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20. Change of patient perceptions of chemotherapy side effects in breast and ovarian cancer patients

Author

Ataseven, B., primary, Frindte, J., additional, Harter, P., additional, Göke, G., additional, Holtschmidt, J., additional, Vogt, C., additional, Traut, A., additional, Vincenzo, B., additional, Vincent, M., additional, Florian, H., additional, Kuemmel, S., additional, Prader, S., additional, Sporkmann, M., additional, Schneider, S., additional, and du Bois, A., additional

Published
2017
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36. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Author

Sabino De Placido, Ciro Gallo, Michelino De Laurentiis, Giancarlo Bisagni, Grazia Arpino, Maria Giuseppa Sarobba, Ferdinando Riccardi, Antonio Russo, Lucia Del Mastro, Alessio Aligi Cogoni, Francesco Cognetti, Stefania Gori, Jennifer Foglietta, Antonio Frassoldati, Domenico Amoroso, Lucio Laudadio, Luca Moscetti, Filippo Montemurro, Claudio Verusio, Antonio Bernardo, Vito Lorusso, Adriano Gravina, Gabriella Moretti, Rossella Lauria, Antonella Lai, Carmela Mocerino, Sergio Rizzo, Francesco Nuzzo, Paolo Carlini, Francesco Perrone, Antonello Accurso, Biagio Agostara, Michele Aieta, Oscar Alabiso, Maria Grazia Alicicco, Dino Amadori, Laura Amaducci, Gianna Amiconi, Giustino Antuzzi, Mara Ardine, Antonio Ardizzoia, Caterina Aversa, Giuseppe Badalamenti, Sandro Barni, Carlo Basurto, Rossana Berardi, Cinzia Bergamasco, Paolo Bidoli, Claudia Bighin, Edoardo Biondi, Corrado Boni, Karen Borgonovo, Mario Botta, Stefano Bravi, Paolo Bruzzi, Giuseppe Buono, Alfredo Butera, Alessia Caldara, Giampiero Candeloro, Claudia Cappelletti, Cinzia Cardalesi, Elisabetta Carfora, Anna Cariello, Francesco Carrozza, Giacomo Cartenì, Michele Caruso, Virginia Casadei, Claudia Casanova, Luigi Castori, Luigi Cavanna, Giovanna Cavazzini, Marina Cazzaniga, Mario Chilelli, Paolo Chiodini, Silvia Chiorrini, Fortunato Ciardiello, Mariangela Ciccarese, Saverio Cinieri, Mario Clerico, Mariarosa Coccaro, Mario Comande, Claudia Corbo, Giuseppina Cortino, Stefania Cusenza, Gennaro Daniele, Alfonso Maria D'arco, Giuliana D'auria, Claudio Dazzi, Carmine De Angelis, Filippo de Braud, Gianfranco De Feo, Andrea De Matteis, Michele De Tursi, Anna Di Blasio, Giuseppe di Lucca, Liberato Di Lullo, Francesca Di Rella, Gianfranco Di Renzo, Pia Di Stefano, Aida Di Stefano, Anna Diana, Sara Donati, Agnese Fabbri, Alessandra Fabi, Marina Faedi, Gabriella Farina, Antonio Farris, Antonio Febbraro, Palma Fedele, Piera Federico, Francesco Ferraù, Gianluigi Ferretti, Antonella Ferro, Irene Floriani, Rosachiara Forcignanò, Samantha Forciniti, Valeria Forestieri, Gianni Fornari, Michela Frisinghelli, Vittorio Fusco, Giulia Gallizzi, Antonio Galvano, Antonio Gambardella, Angelo Gambi, Vittorio Gebbia, Erika Gervasi, Mara Ghilardi, Alice Giacobino, Giovanni Giardina, Francesco Giotta, Sara Giraudi, Mario Giuliano, Antonino Grassadonia, Donatella Grasso, Federica Grosso, Lorenzo Guizzaro, Pasquale Incoronato, Lorena Incorvaia, Giovanni Iodice, Nicla La Verde, Vincenzo Labonia, Gabriella Landi, Agnese Latorre, Vita Leonardi, Alessia Levaggi, Gennaro Limite, Linda Lina Bascialla, Lorenzo Livi, Evaristo Maiello, Daniela Mandelli, Ilaria Marcon, Daniela Menon, Michele Montedoro, Lucia Moraca, Anna Moretti, Maria Grazia Morritti, Patrizia Morselli, Antonella Mura, Silvia Mura, Michela Musacchio, Alberto Muzio, Donato Natale, Clara Natoli, Cinzia Nigro, Cecilia Nisticò, Antonio Nuzzo, Michele Orditura, Laura Orlando, Carmen Pacilio, Giuliano Palumbo, Raffaella Palumbo, Felice Pasini, Emanuela Paterno, Antonio Pazzola, Silvia Pelliccioni, Matilde Pensabene, Davide Perroni, Angela Pesenti Gritti, Fausto Petrelli, Maria Carmela Piccirillo, Graziella Pinotti, Claudia Pogliani, Davide Poli, Sonia Prader, Francesco Recchia, Daniele Rizzi, Carmen Romano, Rosalba Rossello, Chiara Rossini, Giuseppina Salvucci, Valeria Sanna, Alessandra Santini, Silvana Saracchini, Clementina Savastano, Giovanni Scambia, Francesco Schettini, Paola Schiavone, Alessio Schirone, Elena Seles, Simona Signoriello, Giuseppe Signoriello, Rosa Rita Silva, Antonia Silvestri, Vittorio Simeon, Ilaria Spagnoletti, Stefano Tamberi, Cristina Teragni, Verena Thalmann, Renato Thomas, Guglielmo Thomas, Amelia Tienghi, Nicola Tinari, Vincenza Tinessa, Federica Tomei, Giuseppe Tonini, Valter Torri, Divina Traficante, Marianna Tudini, Monica Turazza, Roberto Vignoli, Maria Giuseppa Vitale, Alessandra Zacchia, Pasquale Zagarese, Alda Zanni, Laura Zavallone, Maria Zavettieri, Alessandra Zoboli, De Placido, S., Gallo, C., De Laurentiis, M., Bisagni, G., Arpino, G., Sarobba, M. G., Riccardi, F., Russo, A., Del Mastro, L., Cogoni, A. A., Cognetti, F., Gori, S., Foglietta, J., Frassoldati, A., Amoroso, D., Laudadio, L., Moscetti, L., Montemurro, F., Verusio, C., Bernardo, A., Lorusso, V., Gravina, A., Moretti, G., Lauria, R., Lai, A., Mocerino, C., Rizzo, S., Nuzzo, F., Carlini, P., Perrone, F., Accurso, A., Agostara, B., Aieta, M., Alabiso, O., Alicicco, M. G., Amadori, D., Amaducci, L., Amiconi, G., Antuzzi, G., Ardine, M., Ardizzoia, A., Aversa, C., Badalamenti, G., Barni, S., Basurto, C., Berardi, R., Bergamasco, C., Bidoli, P., Bighin, C., Biondi, E., Boni, C., Borgonovo, K., Botta, M., Bravi, S., Bruzzi, P., Buono, G., Butera, A., Caldara, A., Candeloro, G., Cappelletti, C., Cardalesi, C., Carfora, E., Cariello, A., Carrozza, F., Carteni, G., Caruso, M., Casadei, V., Casanova, C., Castori, L., Cavanna, L., Cavazzini, G., Cazzaniga, M., Chilelli, M., Chiodini, P., Chiorrini, S., Ciardiello, F., Ciccarese, M., Cinieri, S., Clerico, M., Coccaro, M., Comande, M., Corbo, C., Cortino, G., Cusenza, S., Daniele, G., D'Arco, A. M., D'Auria, G., Dazzi, C., De Angelis, C., de Braud, F., De Feo, G., De Matteis, Ma., De Tursi, M., Di Blasio, A., di Lucca, G., Di Lullo, L., Di Rella, F., Di Renzo, G., Di Stefano, P., Di Stefano, A., Diana, A., Donati, S., Fabbri, A., Fabi, A., Faedi, M., Farina, G., Farris, A., Febbraro, A., Fedele, P., Federico, P., Ferrau, F., Ferretti, G., Ferro, A., Floriani, I., Forcignano, R., Forciniti, S., Forestieri, V., Fornari, G., Frisinghelli, M., Fusco, V., Gallizzi, G., Galvano, A., Gambardella, A., Gambi, A., Gebbia, V., Gervasi, E., Ghilardi, M., Giacobino, A., Giardina, G., Giotta, F., Giraudi, S., Giuliano, M., Grassadonia, A., Grasso, D., Grosso, F., Guizzaro, L., Incoronato, P., Incorvaia, L., Iodice, G., La Verde, N., Labonia, V., Landi, G., Latorre, A., Leonardi, V., Levaggi, A., Limite, G., Lina Bascialla, L., Livi, L., Maiello, E., Mandelli, D., Marcon, I., Menon, D., Montedoro, M., Moraca, L., Moretti, A., Morritti, M. G., Morselli, P., Mura, A., Mura, S., Musacchio, M., Muzio, A., Natale, D., Natoli, C., Nigro, C., Nistico, C., Nuzzo, A., Orditura, M., Orlando, L., Pacilio, C., Palumbo, G., Palumbo, R., Pasini, F., Paterno, E., Pazzola, A., Pelliccioni, S., Pensabene, M., Perroni, D., Pesenti Gritti, A., Petrelli, F., Piccirillo, M. C., Pinotti, G., Pogliani, C., Poli, D., Prader, S., Recchia, F., Rizzi, D., Romano, C., Rossello, R., Rossini, C., Salvucci, G., Sanna, V., Santini, A., Saracchini, S., Savastano, C., Scambia, G., Schettini, F., Schiavone, P., Schirone, A., Seles, E., Signoriello, S., Signoriello, G., Silva, R. R., Silvestri, A., Simeon, V., Spagnoletti, I., Tamberi, S., Teragni, C., Thalmann, V., Thomas, R., Thomas, G., Tienghi, A., Tinari, N., Tinessa, V., Tomei, F., Tonini, G., Torri, V., Traficante, D., Tudini, M., Turazza, M., Vignoli, R., Vitale, M. G., Zacchia, A., Zagarese, P., Zanni, A., Zavallone, L., Zavettieri, M., Zoboli, A., De Placido, Sabino, Gallo, Ciro, De Laurentiis, Michelino, Bisagni, Giancarlo, Arpino, Grazia, Sarobba, Maria Giuseppa, Riccardi, Ferdinando, Russo, Antonio, Del Mastro, Lucia, Cogoni, Alessio Aligi, Cognetti, Francesco, Gori, Stefania, Foglietta, Jennifer, Frassoldati, Antonio, Amoroso, Domenico, Laudadio, Lucio, Moscetti, Luca, Montemurro, Filippo, Verusio, Claudio, Bernardo, Antonio, Lorusso, Vito, Gravina, Adriano, Moretti, Gabriella, Lauria, Rossella, Lai, Antonella, Mocerino, Carmen, Rizzo, Sergio, Nuzzo, Francesco, Carlini, Paolo, Perrone, Francesco, Accurso, Antonello, Agostara, Biagio, Aieta, Michele, Alabiso, Oscar, Alicicco, Maria Grazia, Amadori, Dino, Amaducci, Laura, Amiconi, Gianna, Antuzzi, Giustino, Ardine, Mara, Ardizzoia, Antonio, Aversa, Caterina, Badalamenti, Giuseppe, Barni, Sandro, Basurto, Carlo, Berardi, Rossana, Bergamasco, Cinzia, Bidoli, Paolo, Bighin, Claudia, Biondi, Edoardo, Boni, Corrado, Borgonovo, Karen, Botta, Mario, Bravi, Stefano, Bruzzi, Paolo, Buono, Giuseppe, Butera, Alfredo, Caldara, Alessia, Candeloro, Giampiero, Cappelletti, Claudia, Cardalesi, Cinzia, Carfora, Elisabetta, Cariello, Anna, Carrozza, Francesco, Cartenì, Giacomo, Caruso, Michele, Casadei, Virginia, Casanova, Claudia, Castori, Luigi, Cavanna, Luigi, Cavazzini, Giovanna, Cazzaniga, Marina, Chilelli, Mario, Chiodini, Paolo, Chiorrini, Silvia, Ciardiello, Fortunato, Ciccarese, Mariangela, Cinieri, Saverio, Clerico, Mario, Coccaro, Mariarosa, Comande, Mario, Corbo, Claudia, Cortino, Giuseppina, Cusenza, Stefania, Daniele, Gennaro, D'arco, Alfonso Maria, D'auria, Giuliana, Dazzi, Claudio, De Angelis, Carmine, de Braud, Filippo, De Feo, Gianfranco, De Matteis, Andrea, De Tursi, Michele, Di Blasio, Anna, di Lucca, Giuseppe, Di Lullo, Liberato, Di Rella, Francesca, Di Renzo, Gianfranco, Di Stefano, Pia, Di Stefano, Aida, Diana, Anna, Donati, Sara, Fabbri, Agnese, Fabi, Alessandra, Faedi, Marina, Farina, Gabriella, Farris, Antonio, Febbraro, Antonio, Fedele, Palma, Federico, Piera, Ferraù, Francesco, Ferretti, Gianluigi, Ferro, Antonella, Floriani, Irene, Forcignanò, Rosachiara, Forciniti, Samantha, Forestieri, Valeria, Fornari, Gianni, Frisinghelli, Michela, Fusco, Vittorio, Gallizzi, Giulia, Galvano, Antonio, Gambardella, Antonio, Gambi, Angelo, Gebbia, Vittorio, Gervasi, Erika, Ghilardi, Mara, Giacobino, Alice, Giardina, Giovanni, Giotta, Francesco, Giraudi, Sara, Giuliano, Mario, Grassadonia, Antonino, Grasso, Donatella, Grosso, Federica, Guizzaro, Lorenzo, Incoronato, Pasquale, Incorvaia, Lorena, Iodice, Giovanni, La Verde, Nicla, Labonia, Vincenzo, Landi, Gabriella, Latorre, Agnese, Leonardi, Vita, Levaggi, Alessia, Limite, Gennaro, Lina Bascialla, Linda, Livi, Lorenzo, Maiello, Evaristo, Mandelli, Daniela, Marcon, Ilaria, Menon, Daniela, Montedoro, Michele, Moraca, Lucia, Moretti, Anna, Morritti, Maria Grazia, Morselli, Patrizia, Mura, Antonella, Mura, Silvia, Musacchio, Michela, Muzio, Alberto, Natale, Donato, Natoli, Clara, Nigro, Cinzia, Nisticò, Cecilia, Nuzzo, Antonio, Orditura, Michele, Orlando, Laura, Pacilio, Carmen, Palumbo, Giuliano, Palumbo, Raffaella, Pasini, Felice, Paterno, Emanuela, Pazzola, Antonio, Pelliccioni, Silvia, Pensabene, Matilde, Perroni, Davide, Pesenti Gritti, Angela, Petrelli, Fausto, Piccirillo, Maria Carmela, Pinotti, Graziella, Pogliani, Claudia, Poli, Davide, Prader, Sonia, Recchia, Francesco, Rizzi, Daniele, Romano, Carmen, Rossello, Rosalba, Rossini, Chiara, Salvucci, Giuseppina, Sanna, Valeria, Santini, Alessandra, Saracchini, Silvana, Savastano, Clementina, Scambia, Giovanni, Schettini, Francesco, Schiavone, Paola, Schirone, Alessio, Seles, Elena, Signoriello, Simona, Signoriello, Giuseppe, Silva, Rosa Rita, Silvestri, Antonia, Simeon, Vittorio, Spagnoletti, Ilaria, Tamberi, Stefano, Teragni, Cristina, Thalmann, Verena, Thomas, Renato, Thomas, Guglielmo, Tienghi, Amelia, Tinari, Nicola, Tinessa, Vincenza, Tomei, Federica, Tonini, Giuseppe, Torri, Valter, Traficante, Divina, Tudini, Marianna, Turazza, Monica, Vignoli, Roberto, Vitale, Maria Giuseppa, Zacchia, Alessandra, Zagarese, Pasquale, Zanni, Alda, Zavallone, Laura, Zavettieri, Maria, Zoboli, Alessandra, Mocerino, Carmela, D'Arco, Alfonso Maria, D'Auria, Giuliana, De Placido, S, Gallo, C, De Laurentiis, M, Bisagni, G, Arpino, G, Sarobba, M, Riccardi, F, Russo, A, Del Mastro, L, Cogoni, A, Cognetti, F, Gori, S, Foglietta, J, Frassoldati, A, Amoroso, D, Laudadio, L, Moscetti, L, Montemurro, F, Verusio, C, Bernardo, A, Lorusso, V, Gravina, A, Moretti, G, Lauria, R, Lai, A, Mocerino, C, Rizzo, S, Nuzzo, F, Carlini, P, Perrone, F, Accurso, A, Agostara, B, Aieta, M, Alabiso, O, Alicicco, M, Amadori, D, Amaducci, L, Amiconi, G, Antuzzi, G, Ardine, M, Ardizzoia, A, Aversa, C, Badalamenti, G, Barni, S, Basurto, C, Berardi, R, Bergamasco, C, Bidoli, P, Bighin, C, Biondi, E, Boni, C, Borgonovo, K, Botta, M, Bravi, S, Bruzzi, P, Buono, G, Butera, A, Caldara, A, Candeloro, G, Cappelletti, C, Cardalesi, C, Carfora, E, Cariello, A, Carrozza, F, Carteni, G, Caruso, M, Casadei, V, Casanova, C, Castori, L, Cavanna, L, Cavazzini, G, Cazzaniga, M, Chilelli, M, Chiodini, P, Chiorrini, S, Ciardiello, F, Ciccarese, M, Cinieri, S, Clerico, M, Coccaro, M, Comande, M, Corbo, C, Cortino, G, Cusenza, S, Daniele, G, D'Arco, A, D'Auria, G, Dazzi, C, De Angelis, C, de Braud, F, De Feo, G, De Matteis, A, De Tursi, M, Di Blasio, A, di Lucca, G, Di Lullo, L, Di Rella, F, Di Renzo, G, Di Stefano, P, Di Stefano, A, Diana, A, Donati, S, Fabbri, A, Fabi, A, Faedi, M, Farina, G, Farris, A, Febbraro, A, Fedele, P, Federico, P, Ferrau, F, Ferretti, G, Ferro, A, Floriani, I, Forcignano, R, Forciniti, S, Forestieri, V, Fornari, G, Frisinghelli, M, Fusco, V, Gallizzi, G, Galvano, A, Gambardella, A, Gambi, A, Gebbia, V, Gervasi, E, Ghilardi, M, Giacobino, A, Giardina, G, Giotta, F, Giraudi, S, Giuliano, M, Grassadonia, A, Grasso, D, Grosso, F, Guizzaro, L, Incoronato, P, Incorvaia, L, Iodice, G, La Verde, N, Labonia, V, Landi, G, Latorre, A, Leonardi, V, Levaggi, A, Limite, G, Lina Bascialla, L, Livi, L, Maiello, E, Mandelli, D, Marcon, I, Menon, D, Montedoro, M, Moraca, L, Moretti, A, Morritti, M, Morselli, P, Mura, A, Mura, S, Musacchio, M, Muzio, A, Natale, D, Natoli, C, Nigro, C, Nistico, C, Nuzzo, A, Orditura, M, Orlando, L, Pacilio, C, Palumbo, G, Palumbo, R, Pasini, F, Paterno, E, Pazzola, A, Pelliccioni, S, Pensabene, M, Perroni, D, Pesenti Gritti, A, Petrelli, F, Piccirillo, M, Pinotti, G, Pogliani, C, Poli, D, Prader, S, Recchia, F, Rizzi, D, Romano, C, Rossello, R, Rossini, C, Salvucci, G, Sanna, V, Santini, A, Saracchini, S, Savastano, C, Scambia, G, Schettini, F, Schiavone, P, Schirone, A, Seles, E, Signoriello, S, Signoriello, G, Silva, R, Silvestri, A, Simeon, V, Spagnoletti, I, Tamberi, S, Teragni, C, Thalmann, V, Thomas, R, Thomas, G, Tienghi, A, Tinari, N, Tinessa, V, Tomei, F, Tonini, G, Torri, V, Traficante, D, Tudini, M, Turazza, M, Vignoli, R, Vitale, M, Zacchia, A, Zagarese, P, Zanni, A, Zavallone, L, Zavettieri, M, and Zoboli, A

Subjects
Oncology, Receptor, ErbB-2, Settore MED/06 - Oncologia Medica, letrozole, law.invention, Adjuvant anastrozole, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Exemestane, law, exemestane, tamoxifen, breast cancer, Antineoplastic Combined Chemotherapy Protocols, 030212 general & internal medicine, Aromatase Inhibitors, Letrozole, Hazard ratio, Middle Aged, Receptors, Estrogen, Tolerability, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, Receptors, Progesterone, Breast Neoplasm, Human, medicine.drug, medicine.medical_specialty, Socio-culturale, Anastrozole, Breast Neoplasms, Disease-Free Survival, Drug Administration Schedule, 03 medical and health sciences, Breast cancer, Internal medicine, medicine, Aromatase Inhibitor, Humans, Aged, Antineoplastic Combined Chemotherapy Protocol, Androstadiene, business.industry, medicine.disease, Androstadienes, chemistry, business, Tamoxifen
Abstract

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46–72), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88·5% (95% CI 86·7–90·0) with the switch strategy and 89·8% (88·2–91·2) with upfront treatment (hazard ratio 0·89, 95% CI 0·73–1·08; p=0·23). 5-year disease-free survival was 90·0% (95% CI 87·9–91·7) with anastrozole (124 events), 88·0% (85·8–89·9) with exemestane (148 events), and 89·4% (87·3 to 91·1) with letrozole (129 events; p=0·24). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3–4 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3–4 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency.

Published
2018

37. Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations

Author

Tim Niehues, Catherine Waruiru, Conleth Feighery, Uwe Schauer, Virginie Courteille, Kai Lehmberg, Ingo Müller, I. Esteves, Henner Morbach, Michael Borte, Patrick Hundsdoerfer, Klaus Schwarz, Ewelina Gowin, Alessandro Aiuti, Andreas Holbro, Federica Barzaghi, João Farela Neves, Dagmar Graf, Hannah Tamary, Veneta Milenova, Benedikt Boetticher, Eleonora Gambineri, Vera Goda, Alia Eldash, Jan-Christian Wasmuth, Fabio Candotti, Svetlana O. Sharapova, Markus Metzler, Juergen Brunner, Anna Hilfanova, Brindusa Ruxandra Capilna, Pere Soler-Palacín, Arnau Antolí, Horst von Bernuth, Vassilios Lougaris, Maria Carrabba, Bernd H. Belohradsky, Julian Thalhammer, Nathalie de Vergnes, Peter Olbrich, Peter Kopač, Leif G. Hanitsch, Alexandra Nieters, Filomeen Haerynck, Juliana Gabzdilova, Sezin Aydemir, Rabab El Hawary, Patrick F.K. Yong, Maria Giovanna Danieli, Alberto Tommasini, Sandra Steinmann, Ulrich Baumann, Figen Dogu, Elisabeth Förster-Waldl, Carolina Marasco, Donato Amodio, Lorenzo Lodi, Xavier Solanich, Caterina Cancrini, Brigita Sitkauskiene, Torsten Witte, Clementina Vanessa, Nima Rezaei, Jean-Christophe Goffard, Kirsten Wittke, Emmanouil Liatsis, Helen Baxendale, Susana L. Silva, Bodo Grimbacher, Henrike Ritterbusch, Evangelia Farmaki, Safa Meshaal, Sujal Ghosh, Larysa Kostyuchenko, David Edgar, Simone Cesaro, R Zeuner, Nerea Salmón Rodríguez, Isabella Quinti, Stephan Ehl, Pauline Brosselin, Joerg C. Henes, Pilar Llobet Agulló, Rosa Maria Dellepiane, Andrea Meinhardt, Marina Kojić, Georgios Sogkas, Stephan Borte, Catharina Schuetz, Suheyla Ocak, Karin Marschall, Lukas M. Gasteiger, Stefan Raffac, Sofia Tantou, Sadia Noorani, Matthaios Speletas, Philippe Randrianomenjanahary, Ursula Holzer, Ayca Kiykim, Johannes G. Liese, Angelo Vacca, Gisela Fecker, Ekrem Unal, Koen J. van Aerde, Alba Parra-Martínez, Kaan Boztug, Sophie Stiehler, Sybille Landwehr-Kenzel, Claudio Pignata, Jennifer Neubert, Janine Reichenbach, Shahnaz Parvin, Sarah Goddard, Andrea Schroll, Dirk Holzinger, Asghar Aghamohammadi, Hassan Abolhassani, Johannes Trück, Estela Paz-Artal, Shereen M. Reda, Anna Shcherbina, Maria Raptaki, Jaroslava Orosova, Beata Wolska-Kuśnierz, Tessa Kerre, Gerrit Ahrenstorf, Ben Zion Garty, Dirk Foell, Benjamin Becker, Ulrike F. Demel, Androniki Kapousouzi, Abraham Rutgers, Klaus Warnatz, Gemma Rocamora Blanch, Stephan Rusch, Luis M. Allende, Dalia Abd Elaziz, Safa Baris, Jorisvan Montfrans, Dominik T. Schneider, Raphael Scheible, Juana Gil-Herrera, Gerhard Kindle, Annarosa Soresina, Giovanna Fabio, Uwe Wintergerst, Emilia Faria, Maria Fasshauer, Silvia Ricci, Aisha Elmarsafy, Barbara Pietrucha, Carsten Speckmann, Nizar Mahlaoui, Ulrich Heininger, Isabelle Meyts, Matthew Buckland, Efimia Papadopoulou-Alataki, Robin Kobbe, A Herwadkar, Sebastian F. N. Bode, Ali Sobh, László Maródi, Baldassarre Martire, Chiara Azzari, Maximilian Heeg, Katja Masjosthusmann, Michael H. Albert, Matteo Chinello, Juan Luis Santos-Pérez, Aarnoud Huissoon, Tanya I. Coulter, Hendrik Schulze-Koops, Norbert Graf, Radwa Alkady, Jolanta Bernatoniene, Seraina Prader, Alenka Gagro, Joachim Roesler, Taco W. Kuijpers, Ewa Więsik-Szewczyk, Maria Elena Maccari, Conrad Ferdinand Lippert, Miriam González-Amores, Johannes Dirks, Daniel E Pleguezuelo, Christof M. Kramm, Anders Fasth, Volker Schuster, Olov Ekwall, Nikolaus Rieber, Javier Carbone, Petra Kaiser-Labusch, Diana Ernst, Lucia Augusta Baselli, Luis Ignacio Gonzalez-Granado, Maria Kanariou, Stefanie S. V. Henriet, Sigune Goldacker, Kerstin Felgentreff, Oana Joean, Fine Roosens, Fabian Hauck, Eva C. Schwaneck, Milos Jesenak, Manfred Hoenig, Lenka Kapustova, Christoph Boesecke, Alain Fischer, Sara Pereira da Silva, Julia Körholz, Ansgar Schulz, Carolynne Schwarze-Zander, Mikko Seppänen, Nermeen Galal, Nora Naumann-Bartsch, Tomaz Garcez, Peter Ciznar, Klara M. Posfay-Barbe, Zelimir Pavle Eric, Reinhold E. Schmidt, Hermann J. Girschick, Sabine Heine, Anika-Kerstin Biegner, Annick A. J. M. van de Ven, Stefan Schreiber, J. Merlijn van den Berg, Nurit Assia Batzir, Alexandra Jablonka, Kim Stol, Gregor Dückers, Antonios G.A. Kolios, Ioannis Kakkas, Christian Klemann, Marina N. Guseva, Sofia Grigoriadou, Elif Karakoc-Aydiner, Antonio Marzollo, Peter D. Arkwright, Urs C. Steiner, Sara Sebnem Kilic, Romina Dieli-Crimi, Gergely Kriván, Monika Sparber-Sauer, Marco Cazzaniga, Fulvio Porta, Paraskevi Maggina, Tomas Milota, Robbert G. M. Bredius, Martine Pergent, Klaus Tenbrock, Jana Pachlopnik Schmid, Florentia Dimitriou, Cathal Laurence Steele, Helen Bourne, Anna Bobcakova, Gerd Horneff, Judith Potjewijd, Marc Schmalzing, Tobias Ankermann, Paul Ryan, Oksana Boyarchuk, Necil Kutukculer, Carl Friedrich Classen, Zita Chovancová, Moira Thomas, Cinzia Milito, Michaela Bitzenhofer-Grüber, Faranaz Atschekzei, Eva Hlaváčková, Viviana Moschese, Julie Smet, Hans-Hartmut Peter, Carla Teixeira, Sabine M El-Helou, Suzanne de Kruijf Bazen, Helmut Wittkowski, Donate Jakoby, Marina Garcia-Prat, Esther de Vries, Richard Herriot, Sven Kracker, Alessandro Plebani, Lisa Göschl, Laura Hora Marques, Anna Sediva, Jiri Litzman, Mark M. Gompels, Renate Krüger, Şefika İlknur Kökçü Karadağ, Nadine Binder, Anna Szaflarska, Peter Jandus, Lisa Ibberson, Johann Greil, Ulf Schulze-Sturm, Mehtap Sirin, Aydan Ikinciogullari, Edyta Heropolitańska-Pliszka, Michael E. Weiss, Alla Skapenko, Lukas Wisgrill, Hana Alachkar, Uta Behrends, Silvia Sánchez-Ramón, Maria N. Hatzistilianou, Otilia Petrovicova, Darko Richter, Zoreh Nademi, Jürgen K. Rockstroh, Sohilla Lotfy, Markus G. Seidel, Timothy Ronan Leahy, Audra Blažienė, Translational Immunology Groningen (TRIGR), Paediatric Infectious Diseases / Rheumatology / Immunology, AII - Inflammatory diseases, ARD - Amsterdam Reproduction and Development, University of Zurich, Ehl, Stephan, Thalhammer, J., Kindle, G., Nieters, A., Rusch, S., Seppanen, M. R. J., Fischer, A., Grimbacher, B., Edgar, D., Buckland, M., Mahlaoui, N., Ehl, S., Boztug, K., Brunner, J., Demel, U. F., Forster-Waldl, E., Gasteiger, L. M., Goschl, L., Kojic, M., Schroll, A., Seidel, M. G., Wintergerst, U., Wisgrill, L., Sharapova, S. O., Goffard, J. -C., Kerre, T., Meyts, I., Roosens, F., Smet, J., Haerynck, F., Eric, Z. P., Milenova, V., Gagro, A., Richter, D., Chovancova, Z., Hlavackova, E., Litzman, J., Milota, T., Sediva, A., Elaziz, D. A., Alkady, R. S., El Sayed El Hawary, R., Eldash, A. S., Galal, N., Lotfy, S., Meshaal, S. S., Reda, S. M., Sobh, A., Elmarsafy, A., Brosselin, P., Courteille, V., De Vergnes, N., Kracker, S., Pergent, M., Randrianomenjanahary, P., Ahrenstorf, G., Albert, M. H., Ankermann, T., Atschekzei, F., Baumann, U., Becker, B. C., Behrends, U., Belohradsky, B. H., Biegner, A. -K., Binder, N., Bode, S. F. N., Boesecke, C., Boetticher, B., Borte, M., Borte, S., Classen, C. F., Dirks, J., Duckers, G., El-Helou, S., Ernst, D., Fasshauer, M., Fecker, G., Felgentreff, K., Foell, D., Ghosh, S., Girschick, H. J., Goldacker, S., Graf, N., Graf, D., Greil, J., Hanitsch, L. G., Hauck, F., Heeg, M., Heine, S. I., Henes, J. C., Hoenig, M., Holzer, U., Holzinger, D., Horneff, G., Hundsdoerfer, P., Jablonka, A., Jakoby, D., Joean, O., Kaiser-Labusch, P., Klemann, C., Kobbe, R., Korholz, J., Kramm, C. M., Kruger, R., Landwehr-Kenzel, S., Lehmberg, K., Liese, J. G., Lippert, C. F., Maccari, M. E., Masjosthusmann, K., Meinhardt, A., Metzler, M., Morbach, H., Muller, I., Naumann-Bartsch, N., Neubert, J., Niehues, T., Peter, H. -H., Rieber, N., Ritterbusch, H., Rockstroh, J. K., Roesler, J., Schauer, U., Scheible, R., Schmalzing, M., Schmidt, R. E., Schneider, D. T., Schreiber, S., Schuetz, C., Schulz, A., Schulze-Koops, H., Schulze-Sturm, U., Schuster, V., Schwaneck, E. C., Schwarz, K., Schwarze-Zander, C., Sirin, M., Skapenko, A., Sogkas, G., Sparber-Sauer, M., Speckmann, C., Steinmann, S., Stiehler, S., Tenbrock, K., von Bernuth, H., Warnatz, K., Wasmuth, J. -C., Weiss, M., Witte, T., Wittke, K., Wittkowski, H., Zeuner, R. A., Farmaki, E., Hatzistilianou, M. N., Kakkas, I., Kanariou, M. G., Kapousouzi, A., Liatsis, E., Maggina, P., Papadopoulou-Alataki, E., Raptaki, M., Speletas, M., Tantou, S., Goda, V., Krivan, G., Marodi, L., Abolhassani, H., Aghamohammadi, A., Rezaei, N., Feighery, C., Leahy, T. R., Ryan, P., Batzir, N. A., Garty, B. Z., Tamary, H., Aiuti, A., Amodio, D., Azzari, C., Barzaghi, F., Baselli, L. A., Cancrini, C., Carrabba, M., Cazzaniga, M., Cesaro, S., Chinello, M., Danieli, M. G., Dellepiane, R. M., Fabio, G., Gambineri, E., Lodi, L., Lougaris, V., Marasco, C., Martire, B., Marzollo, A., Milito, C., Moschese, V., Pignata, C., Plebani, A., Porta, F., Quinti, I., Ricci, S., Soresina, A., Tommasini, A., Vacca, A., Vanessa, C., Blaziene, A., Sitkauskiene, B., Gowin, E., Heropolitanska-Pliszka, E., Pietrucha, B., Szaflarska, A., Wiesik-Szewczyk, E., Wolska-Kusnierz, B., Esteves, I., Faria, E., Marques, L. H., Neves, J. F., Silva, S. L., Teixeira, C., Pereira da Silva, S., Capilna, B. R., Guseva, M. N., Shcherbina, A., Bobcakova, A., Ciznar, P., Gabzdilova, J., Jesenak, M., Kapustova, L., Orosova, J., Petrovicova, O., Raffac, S., Kopac, P., Allende, L. M., Antoli, A., Blanch, G. R., Carbone, J., Dieli-Crimi, R., Garcia-Prat, M., Gil-Herrera, J., Gonzalez-Granado, L. I., Agullo, P. L., Olbrich, P., Parra-Martinez, A., Paz-Artal, E., Pleguezuelo, D. E., Rodriguez, N. S., Sanchez-Ramon, S., Santos-Perez, J. L., Solanich, X., Soler-Palacin, P., Gonzalez-Amores, M., Ekwall, O., Fasth, A., Bitzenhofer-Gruber, M., Candotti, F., Dimitriou, F., Heininger, U., Holbro, A., Jandus, P., Kolios, A. G. A., Marschall, K., Schmid, J. P., Posfay-Barbe, K. M., Prader, S., Reichenbach, J., Steiner, U. C., Truck, J., Bredius, R. G., de Kruijf- Bazen, S., de Vries, E., Henriet, S. S. V., Kuijpers, T. W., Potjewijd, J., Rutgers, A., Stol, K., van Aerde, K. J., Van den Berg, J. M., van de Ven, A. A. J. M., Montfrans, J., Aydemir, S., Baris, S., Dogu, F., Ikinciogullari, A., Karakoc-Aydiner, E., Kilic, S. S., Kiykim, A., Kokcu Karadag, S. I., Kutukculer, N., Ocak, S., Unal, E., Boyarchuk, O., Hilfanova, A., Kostyuchenko, L. V., Alachkar, H., Arkwright, P. D., Baxendale, H. E., Bernatoniene, J., Coulter, T. I., Garcez, T., Goddard, S., Gompels, M. M., Grigoriadou, S., Herriot, R., Herwadkar, A., Huissoon, A., Ibberson, L., Nademi, Z., Noorani, S., Parvin, S., Steele, C. L., Thomas, M., Waruiru, C., Yong, P. F. K., and Bourne, H.

Subjects
0301 basic medicine, Male, Pediatrics, syndromic, Sex Factor, Disease, registry, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Primary Immunodeficiency Disease, inborn error of immunity, Immunology and Allergy, warning signs, Age Factor, Registries, Family history, presenting symptom, Child, Primary immunodeficiency, Granuloma, autoimmune, immune dysregulation, inflammatory, Adult, Autoimmune Diseases, Female, Humans, Infections, Lymphoproliferative Disorders, Middle Aged, Primary Immunodeficiency Diseases, Sex Factors, Age Factors, 10177 Dermatology Clinic, Infections/epidemiology, 3. Good health, Settore MED/02, Warning signs, Lymphoproliferative Disorder, 2723 Immunology and Allergy, Infection, Human, medicine.medical_specialty, Immunology, 610 Medicine & health, Malignancy, primary immunodeficiency, Autoimmune Disease, 03 medical and health sciences, Immunity, Autoimmune Diseases/epidemiology, medicine, 2403 Immunology, business.industry, warning sign, Common variable immunodeficiency, Granuloma/epidemiology, Immune dysregulation, medicine.disease, Primary Immunodeficiency Diseases/epidemiology, 030104 developmental biology, Lymphoproliferative Disorders/epidemiology, Cohort Studie, business, 030215 immunology
Abstract

BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

Published
2021

38. SUCCOR Risk: Design and Validation of a Recurrence Prediction Index for Early-Stage Cervical Cancer

Author

Manzour, Nabil, Chiva, Luis, Chacón, Enrique, Martin-Calvo, Nerea, Boria, Felix, Minguez, José A, Alcazar, Juan, L, Vanna, Zanagnolo, Denis, Querleu, Mihai, Căpîlna, Anna, Fagotti, Ali, Kucukmetin, Constantijne, Mom, Galina, Chakalova, Shamistan, Aliyev, Mario, Malzoni, Fabrice, Narducci, Octavio, Arencibia, Francesci, Raspagliesi, Tayfun, Toptas, David, Cibula, Dilyara, Kaidarova, Mehmet, Meydanli, Mariana, Tavares, Dmytro, Golub, Anna, Perrone, Robert, Poka, Dimitrios, Tsolakidis, Goran, Vujić, Marcin, Jedryka, Petra, Zusterzeel, Jogchum, Beltman, Frédéric, Goffin, Dimitros, Haidopoulos, Herman, Haller, Robert, Jach, Iryna, Yezhova, Igor, Berlev, Margarida, Bernardino, Rasiah, Bharathan, Maximilian, Lanner, Vladyslav, Sukhin, Jean, G Feron, Robert, Fruscio, Kersti, Kukk, Jordi, Ponce, Nabil, Abdalla, Özgür, Akbayir, Sedat, Akgöl, Elif, Aksahin, Maria, Alonso-Espias, Igor, Aluloski, Claudia, Andrade, Nikola, Badzakov, Rosa, Barrachina, Giorgio, Bogani, Eduard-Aexandru, Bonci, Hélène, Bonsang-Kitzis, Cosima, Brucker, Laura, Cárdenas, Andrea, Casajuana, Pere, Cavalle, Jorge, Cea, Benito, Chiofalo, Gloria, Cordeiro, Pluvio, Coronado, Maria, Cuadra, Javier, Díez, Teresa Diniz da Costa, Santiago, Domingo, Lukas, Dostalek, Fuat, Demirkiran, Diego, Erasun, Mathias, Fehr, Sergi, Fernandez-Gonzalez, Soledad, Fidalgo, Gabriel, Fiol, Khadra, Galaal, José, García, Gerhard, Gebauer, Fabio, Ghezzi, Juan, Gilabert, Nana, Gomes, Elisabete, Gonçalves, Virginia, Gonzalez, Frederic, Grandjean, Miriam, Guijarro, Frédéric, Guyon, Jolien, Haesen, Gines, Hernandez-Cortes, Sofía, Herrero, Imre, Pete, Ioannis, Kalogiannidis, Erbil, Karaman, Andreas, Kavallaris, Lukasz, Klasa, Ioannis, Kotsopoulos, Stefan, Kovachev, Meelis, Leht, Arantxa, Lekuona, Mathieu, Luyckx, Michael, Mallmann, Gemma, Mancebo, Aljosa, Mandic, Tiermes, Marina, Victor, Martin, María Belén Martín-Salamanca, Alejandra, Martinez, Gesine, Meili, Gustavo, Mendinhos, Mereu, Liliana, Milena, Mitrovic, Sara, Morales, Enrique, Moratalla, Bibiana, Morillas, Eva, Myriokefalitaki, Maja, Pakižimre, Stamatios, Petousis, Laurentiu, Pirtea, Natalia, Povolotskaya, Sonia, Prader, Alfonso, Quesada, Mikuláš, Redecha, Fernando, Roldan, Philip, Rolland, Reeli, Saaron, Cosmin-Paul, Sarac, Jens-Peter, Scharf, Špela, Smrkolj, Rita, Sousa, Artem, Stepanyan, Vladimír, Študent, Carmen, Tauste, Hans, Trum, Taner, Turan, Manuela, Undurraga, Arno, Uppin, Alicia, Vázquez, Ignace, Vergote, George, Vorgias, Ignacio, Zapardiel, Amsterdam Reproduction & Development (AR&D), Obstetrics and gynaecology, CCA - Imaging and biomarkers, Manzour, N, Chiva, L, Chacon, E, Martin-Calvo, N, Boria, F, Minguez, J, Alcazar, J, Zanagnolo, V, Querleu, D, Capilna, M, Fagotti, A, Kucukmetin, A, Mom, C, Chakalova, G, Aliyev, S, Malzoni, M, Narducci, F, Arencibia, O, Raspagliesi, F, Toptas, T, Cibula, D, Kaidarova, D, Meydanli, M, Tavares, M, Golub, D, Perrone, A, Poka, R, Tsolakidis, D, Vujic, G, Jedryka, M, Zusterzeel, P, Beltman, J, Goffin, F, Haidopoulos, D, Haller, H, Jach, R, Yezhova, I, Berlev, I, Bernardino, M, Bharathan, R, Lanner, M, Sukhin, V, Feron, J, Fruscio, R, Kukk, K, Ponce, J, Abdalla, N, Akbayir, O, Akgol, S, Aksahin, E, Alonso-Espias, M, Aluloski, I, Andrade, C, Badzakov, N, Barrachina, R, Bogani, G, Bonci, E, Bonsang-Kitzis, H, Brucker, C, Cardenas, L, Casajuana, A, Cavalle, P, Cea, J, Chiofalo, B, Cordeiro, G, Coronado, P, Cuadra, M, Diez, J, da Costa, T, Domingo, S, Dostalek, L, Demirkiran, F, Erasun, D, Fehr, M, Fernandez-Gonzalez, S, Fidalgo, S, Fiol, G, Galaal, K, Garcia, J, Gebauer, G, Ghezzi, F, Gilabert, J, Gomes, N, Goncalves, E, Gonzalez, V, Grandjean, F, Guijarro, M, Guyon, F, Haesen, J, Hernandez-Cortes, G, Herrero, S, Pete, I, Kalogiannidis, I, Karaman, E, Kavallaris, A, Klasa, L, Kotsopoulos, I, Kovachev, S, Leht, M, Lekuona, A, Luyckx, M, Mallmann, M, Mancebo, G, Mandic, A, Marina, T, Martin, V, Martin-Salamanca, M, Martinez, A, Meili, G, Mendinhos, G, Mereu, L, Mitrovic, M, Morales, S, Moratalla, E, Morillas, B, Myriokefalitaki, E, Pakizimre, M, Petousis, S, Pirtea, L, Povolotskaya, N, Prader, S, Quesada, A, Redecha, M, Roldan, F, Rolland, P, Saaron, R, Sarac, C, Scharf, J, Smrkolj, S, Sousa, R, Stepanyan, A, Student, V, Tauste, C, Trum, H, Turan, T, Undurraga, M, Uppin, A, Vazquez, A, Vergote, I, Vorgias, G, and Zapardiel, I

Subjects
cervical cancer, Cevical cancer, Uterine Cervical Neoplasms, Hysterectomy, Prognosis, Risk Assessment, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], conization, Settore MED/40 - GINECOLOGIA E OSTETRICIA, Oncology, Recurrence, radical hysterectomy, Humans, Female, Surgery, Neoplasm Recurrence, Local, Neoplasm Staging, Retrospective Studies
Abstract

Objective Based on the SUCCOR study database, our primary objective was to identify the independent clinical pathological variables associated with the risk of relapse in patients with stage IB1 cervical cancer who underwent a radical hysterectomy. Our secondary goal was to design and validate a risk predictive index (RPI) for classifying patients depending on the risk of recurrence. Methods Overall, 1116 women were included from January 2013 to December 2014. We randomly divided our sample into two cohorts: discovery and validation cohorts. The test group was used to identify the independent variables associated with relapse, and with these variables, we designed our RPI. The index was applied to calculate a relapse risk score for each participant in the validation group. Results A previous cone biopsy was the most significant independent variable that lowered the rate of relapse (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.17–0.60). Additionally, patients with a tumor diameter >2 cm on preoperative imaging assessment (OR 2.15, 95% CI 1.33–3.5) and operated by the minimally invasive approach (OR 1.61, 95% CI 1.00–2.57) were more likely to have a recurrence. Based on these findings, patients in the validation cohort were classified according to the RPI of low, medium, or high risk of relapse, with rates of 3.4%, 9.8%, and 21.3% observed in each group, respectively. With a median follow-up of 58 months, the 5-year disease-free survival rates were 97.2% for the low-risk group, 88.0% for the medium-risk group, and 80.5% for the high-risk group (p < 0.001). Conclusion Previous conization to radical hysterectomy was the most powerful protective variable of relapse. Our risk predictor index was validated to identify patients at risk of recurrence.

Published
2022
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39. A degranulation assay using Vγ9Vδ2 T cells for the rapid diagnosis of familial hemophagocytic syndromes.

Author

Jorisch-Mühlebach O, Pitts D, Tinner R, Teh HY, Roelli C, Prader S, Vavassori S, and Pachlopnik Schmid J

Subjects
Humans, Female, Male, Receptors, Antigen, T-Cell, gamma-delta metabolism, Receptors, Antigen, T-Cell, gamma-delta genetics, Child, Preschool, Child, Infant, Adolescent, rab27 GTP-Binding Proteins genetics, Membrane Proteins genetics, Membrane Proteins metabolism, Adult, T-Lymphocytes immunology, Reproducibility of Results, Lymphocyte Activation, Sensitivity and Specificity, Munc18 Proteins, Lymphohistiocytosis, Hemophagocytic diagnosis, Lymphohistiocytosis, Hemophagocytic immunology, Lymphohistiocytosis, Hemophagocytic genetics, Cell Degranulation, Killer Cells, Natural immunology, Killer Cells, Natural metabolism
Abstract

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune disorder characterized by uncontrolled lymphocyte and macrophage activation and a subsequent cytokine storm. The timely initiation of immunosuppressive treatment is crucial for survival., Methods: Here, we harnessed Vγ9Vδ2 T cell degranulation to develop a novel functional assay for the diagnosis of HLH. We compared the novel assay with the conventional natural killer (NK) cell stimulation method in terms of efficiency, specificity, and reliability. Our analysis involved 213 samples from 182 individuals, including 23 samples from 12 patients with degranulation deficiency (10 individuals with UNC13D deficiency, 1 with STXBP2 deficiency, and 1 with RAB27A deficiency)., Results: While both tests exhibited 100% sensitivity, the Vγ9Vδ2 T cell degranulation assay showed a superior specificity of 86.2% (n=70) compared to the NK cell degranulation assay, which achieved 78.9% specificity (n=213). The Vγ9Vδ2 T cell degranulation assay offered simpler technical requirements and reduced labor intensity, leading to decreased susceptibility to errors with faster processing times., Discussion: This efficiency stemmed from the sole requirement of dissolving ( E )-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) powder, contrasting with the intricate maintenance of K562 cells necessary for the NK cell degranulation assay. With its diminished susceptibility to errors, we anticipate that the assay will require fewer repetitions of analysis, rendering it particularly well-suited for testing infants., Conclusion: The Vγ9Vδ2 T cell degranulation assay is a user-friendly, efficient diagnostic tool for HLH. It offers greater specificity, reliability, and practicality than established methods. We believe that our present findings will facilitate the prompt, accurate diagnosis of HLH and thus enable rapid treatment and better patient outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jorisch-Mühlebach, Pitts, Tinner, Teh, Roelli, Prader, Vavassori and Pachlopnik Schmid.)

Published
2024
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40. Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia.

Author

García-García A, Pérez de Diego R, Flores C, Rinchai D, Solé-Violán J, Deyà-Martínez À, García-Solis B, Lorenzo-Salazar JM, Hernández-Brito E, Lanz AL, Moens L, Bucciol G, Almuqamam M, Domachowske JB, Colino E, Santos-Perez JL, Marco FM, Pignata C, Bousfiha A, Turvey SE, Bauer S, Haerynck F, Ocejo-Vinyals JG, Lendinez F, Prader S, Naumann-Bartsch N, Pachlopnik Schmid J, Biggs CM, Hildebrand K, Dreesman A, Cárdenes MÁ, Ailal F, Benhsaien I, Giardino G, Molina-Fuentes A, Fortuny C, Madhavarapu S, Conway DH, Prando C, Schidlowski L, Martínez de Saavedra Álvarez MT, Alfaro R, Rodríguez de Castro F, Meyts I, Hauck F, Puel A, Bastard P, Boisson B, Jouanguy E, Abel L, Cobat A, Zhang Q, Casanova JL, Alsina L, and Rodríguez-Gallego C

Subjects
Child, Humans, Adaptor Proteins, Signal Transducing, SARS-CoV-2, Toll-Like Receptor 7, COVID-19 complications, Myeloid Differentiation Factor 88 genetics
Abstract

X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4-dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8-207.8, P < 0.001). The patients' susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia., (© 2023 García García et al.)

Published
2023
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41. Case report: ETS1 gene deletion associated with a low number of recent thymic emigrants in three patients with Jacobsen syndrome.

Author

Trachsel T, Prader S, Steindl K, and Pachlopnik Schmid J

Subjects
Child, Preschool, Humans, Thymus Gland, Gene Deletion, T-Lymphocytes, Phenotype, Proto-Oncogene Protein c-ets-1 genetics, DNA-Binding Proteins genetics, Jacobsen Distal 11q Deletion Syndrome genetics
Abstract

Jacobsen syndrome is a rare genetic disorder associated with a terminal deletion in chromosome 11. The clinical presentation is variable. Although immunodeficiency has been described in patients with Jacobsen syndrome, a clear genotype-phenotype correlation has not yet been established. Here, we report on the immunologic phenotypes of four patients with Jacobsen syndrome. All four patients showed one or more atypical immunologic features. One patient suffered from recurrent viral infections, two patients had experienced a severe bacterial infection and one had received antibiotic prophylaxis since early childhood. One patient had experienced severe, transient immune dysregulation. Hypogammaglobulinemia and low B cell counts were found in two patients, while the number of recent thymic emigrants (CD31+CD45RA+ CD4 cells) was abnormally low in three. When considering the six immune-related genes located within the affected part of chromosome 11 ( ETS1, TIRAP, FLI1, NFRKB, THYN1 , and SNX19 ), only the ETS1 gene was found be deleted in the three patients with low numbers of recent thymic emigrants and non-switched memory B cells. Our findings support the hypothesis whereby Jacobsen syndrome is associated with a combined immunodeficiency with variable presentation. Further investigations of potential genotype-phenotype correlations are warranted and might help to personalize patient management in individuals lacking immune-related genes. In addition, we recommend immunologic follow-up for all patients with Jacobsen syndrome, as immune abnormalities may develop over time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Trachsel, Prader, Steindl and Pachlopnik Schmid.)

Published
2022
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42. Validation analysis of the novel imaging-based prognostic radiomic signature in patients undergoing primary surgery for advanced high-grade serous ovarian cancer (HGSOC).

Author

Fotopoulou C, Rockall A, Lu H, Lee P, Avesani G, Russo L, Petta F, Ataseven B, Waltering KU, Koch JA, Crum WR, Cunnea P, Heitz F, Harter P, Aboagye EO, du Bois A, and Prader S

Subjects
Humans, Neoplasm, Residual, Prognosis, Retrospective Studies, Neoplasm Recurrence, Local diagnostic imaging, Ovarian Neoplasms diagnostic imaging, Ovarian Neoplasms drug therapy, Ovarian Neoplasms surgery
Abstract

Background: Predictive models based on radiomics features are novel, highly promising approaches for gynaecological oncology. Here, we wish to assess the prognostic value of the newly discovered Radiomic Prognostic Vector (RPV) in an independent cohort of high-grade serous ovarian cancer (HGSOC) patients, treated within a Centre of Excellence, thus avoiding any bias in treatment quality., Methods: RPV was calculated using standardised algorithms following segmentation of routine preoperative imaging of patients (n = 323) who underwent upfront debulking surgery (01/2011-07/2018). RPV was correlated with operability, survival and adjusted for well-established prognostic factors (age, postoperative residual disease, stage), and compared to previous validation models., Results: The distribution of low, medium and high RPV scores was 54.2% (n = 175), 33.4% (n = 108) and 12.4% (n = 40) across the cohort, respectively. High RPV scores independently associated with significantly worse progression-free survival (PFS) (HR = 1.69; 95% CI:1.06-2.71; P = 0.038), even after adjusting for stage, age, performance status and residual disease. Moreover, lower RPV was significantly associated with total macroscopic tumour clearance (OR = 2.02; 95% CI:1.56-2.62; P = 0.00647)., Conclusions: RPV was validated to independently identify those HGSOC patients who will not be operated tumour-free in an optimal setting, and those who will relapse early despite complete tumour clearance upfront. Further prospective, multicentre trials with a translational aspect are warranted for the incorporation of this radiomics approach into clinical routine., (© 2021. The Author(s).)

Published
2022
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43. Cell-free tumor DNA, CA125 and HE4 for the objective assessment of tumor burden in patients with advanced high-grade serous ovarian cancer.

Author

Heitz F, Lakis S, Harter P, Heikaus S, Sehouli J, Talwar J, Menon R, Ataseven B, Bertrand M, Schneider S, Mariotti E, Bommert M, Müller JN, Prader S, Leenders F, Hengsbach A, Gloeckner C, Braicu EI, Heukamp LC, du Bois A, and Heuckmann JM

Subjects
Humans, Female, Middle Aged, Aged, Prospective Studies, Tumor Burden, Circulating Tumor DNA blood, Circulating Tumor DNA genetics, Proteins genetics, Tumor Suppressor Protein p53 genetics, Adult, Mutation, Biomarkers, Tumor blood, Biomarkers, Tumor genetics, Membrane Proteins genetics, Membrane Proteins blood, Neoplasm Grading, Cystadenocarcinoma, Serous genetics, Cystadenocarcinoma, Serous pathology, Cystadenocarcinoma, Serous blood, Ascites genetics, Ascites pathology, Ascites blood, Carcinoma, Ovarian Epithelial blood, Carcinoma, Ovarian Epithelial genetics, Carcinoma, Ovarian Epithelial pathology, Cell-Free Nucleic Acids blood, Cell-Free Nucleic Acids genetics, CA-125 Antigen blood, Ovarian Neoplasms genetics, Ovarian Neoplasms blood, Ovarian Neoplasms pathology, WAP Four-Disulfide Core Domain Protein 2 analysis, WAP Four-Disulfide Core Domain Protein 2 metabolism
Abstract

Background: The present prospective study aimed at determining the impact of cell-free tumor DNA (ct-DNA), CA125 and HE4 from blood and ascites for quantification of tumor burden in patients with advanced high-grade serous epithelial ovarian cancer (EOC)., Methods: Genomic DNA was extracted from tumor FFPE and ct-DNA from plasma before surgery and on subsequent post-surgical days. Extracted DNA was subjected to hybrid-capture based next generation sequencing. Blood and ascites were sampled before surgery and on subsequent post-surgical days. 20 patients (10 undergoing complete resection (TR0), 10 undergoing incomplete resection (TR>0)) were included., Results: The minor allele frequency (MAF) of TP53 mutations in ct-DNA of all patients with TR0 decreased significantly, compared to only one patient with TR>0. It was not possible to distinguish between patients with TR0 and patients with TR>0, using CA125 and HE4 from blood and ascites., Conclusions: Based upon the present findings, ct-DNA assessment in patients with high-grade serous EOC might help to better determine disease burden compared to standard tumor markers. Further studies should prospectively evaluate whether this enhancement of accuracy can help to optimize management of patients with EOC., Competing Interests: FH: Travel grants: AstraZeneca, Tesaro, Roche; Honoraria: Roche, AstraZeneca; Clovis, Advisory: Roche; SL: personal fees from NEO New Oncology GmbH, personal fees from BioNTech Diagnostics, personal fees from Definiens GmbH; PH: Honoraria: Roche, AstraZeneca, Tesaro; Advisory: Roche, AstraZeneca, Tesaro, PharmaMar, Lilly; SH: none; JS: HONORARIA: Astra Zeneca, Eisai, Clovis, Olympus, Johnsons and Johnson, PharmaMar, Pfizer, TEVA, TESARO, MSD; CONSULTING OR ADVISORY ROLE: Astra Zeneca, Clovis, Lilly, PharmaMar, Pfizer, Roche, TESARO, MSD; RESEARCH FUNDING: Astra Zeneca, Clovis, Merck, Bayer, PharmaMar, Pfizer, TESARO, MSD; TRAVEL, ACCOMODATIONS, EXPENSES: Astra Zeneca, Clovis, PharmaMar, Roche, Pfizer, TESARO, MSD; JT: employed at New Oncology; RM: employed at New Oncology; BA: reports receiving honoraria from Roche, Tesaro, Clovis, AstraZeneca, and Celgene for lectures, and is an unpaid consultant/advisory board member for Roche and Amgen; MB employed at New Oncology; SS: none; EM: employed at New Oncology; MB: Travel support from prIME Oncology; JNM: employed at New Oncology; SP: none; FL: employed at New Oncology; AH: none; CG: employed at New Oncology; EIB: reports receiving honoraria for advisory board and educational activities from AstraZeneca, Clovis, Tesaro, GSK, Roche Pharma, Incyte, Eisai, MSD, Abbvie; reports receiving travel costs from Clovis, Tesaro, Roche Pharma; LCH: employed at New Oncology; AdB: reports honorary for advisory board and educational activities for Roche, Astra Zeneca, Tesaro, Clovis, Biocad, and Genmab; JMH: employed at New Oncology. That the competing interests does not alter our adherence to PLOS ONE policies on sharing data and materials.

Published
2022
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44. Cell-Free-DNA-Based Copy Number Index Score in Epithelial Ovarian Cancer-Impact for Diagnosis and Treatment Monitoring.

Author

Braicu EI, du Bois A, Sehouli J, Beck J, Prader S, Kulbe H, Eiben B, Harter P, Traut A, Pietzner K, Glaubitz R, Ataseven B, Chekerov R, Keck C, Winkler T, Heikaus S, Gellendin P, Schütz E, and Heitz F

Abstract

Background: Chromosomal instability, a hallmark of cancer, results in changes in the copy number state. These deviant copy number states can be detected in the cell-free DNA (cfDNA) and provide a quantitative measure of the ctDNA levels by converting cfDNA next-generation sequencing results into a genome-wide copy number instability score (CNI-Score). Our aim was to determine the role of the CNI-Score in detecting epithelial ovarian cancer (EOC) and its role as a marker to monitor the response to treatment., Methods: Blood samples were prospectively collected from 109 patients with high-grade EOC. cfDNA was extracted and analyzed using a clinical-grade assay designed to calculate a genome-wide CNI-Score from low-coverage sequencing data. Stored data from 241 apparently healthy controls were used as a reference set., Results: Comparison of the CNI-Scores of primary EOC patients versus controls yielded sensitivities of 91% at a specificity of 95% to detect OC, respectively. Significantly elevated CNI-Scores were detected in primary (median: 87, IQR: 351) and recurrent (median: 346, IQR: 1891) blood samples. Substantially reduced CNI-Scores were detected after primary debulking surgery. Using a cut-off of 24, a diagnostic sensitivity of 87% for primary and recurrent EOC was determined at a specificity of 95%. CNI-Scores above this threshold were detected in 21/23 primary tumor (91%), 36/42 of platinum-eligible recurrent (85.7%), and 19/22 of non-platinum-eligible recurrent (86.3%) samples, respectively., Conclusion: ctDNA-quantification based on genomic instability determined by the CNI-Score was a biomarker with high diagnostic accuracy in high-grade EOC. The applied assay might be a promising tool for diagnostics and therapy monitoring, as it requires no a priori information about the tumor.

Published
2021
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45. X-Linked Lymphoproliferative Disease Mimicking Multisystem Inflammatory Syndrome in Children-A Case Report.

Author

Prader S, Ritz N, Baleydier F, Andre MC, Stähli N, Schmid K, Schmid H, Woerner A, Diesch T, Meyer Sauteur PM, Trück J, Gebistorf F, Opitz L, Killian MP, Marchetti T, Vavassori S, Blanchard-Rohner G, Mc Lin V, Grazioli S, and Pachlopnik Schmid J

Abstract

Most children with a SARS-CoV-2 infection are asymptomatic or exhibit mild symptoms. However, a small number of children develop features of substantial inflammation temporarily related to the COVID-19 also called multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), clinically similar to Kawasaki disease, toxic shock syndrome and hemophagocytic lymphohistiocytosis (HLH). It is well-known that genetic pre-disposition plays an important role in virally-triggered diseases such as Epstein-Barr virus (EBV)-associated HLH, while this has not yet been established for patients with MIS-C. Here we describe a male patient fulfilling the diagnostic criteria of MIS-C, who was initially treated according to current consensus guidelines. Presence of hypofibrinogenemia, normal lymphocyte counts and C-reactive protein, but substantial hyperferritinemia distinguish this patient from others with MIS-C. The clinical course following initial presentation with acute respiratory distress syndrome was marked by fatal liver failure in the context of EBV-associated HLH despite treatment with steroids, intravenous immunoglobulins, interleukin (IL)-1 receptor blockade and eventually HLH-directed treatment. X-linked lymphoproliferative disease type 1 (XLP1), a subtype of primary HLH was diagnosed in this patient post-mortem. This case report highlights the importance of including HLH in the differential diagnosis in MIS-C with severe disease course to allow specific, risk-adapted treatment and genetic counseling., Competing Interests: JP is member of a data monitoring committee for Leniolisib for Novartis and advisory board for Emapalumab for SOBI. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Prader, Ritz, Baleydier, Andre, Stähli, Schmid, Schmid, Woerner, Diesch, Meyer Sauteur, Trück, Gebistorf, Opitz, Killian, Marchetti, Vavassori, Blanchard-Rohner, Mc Lin, Grazioli and Pachlopnik Schmid.)

Published
2021
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46. Swiss newborn screening for severe T and B cell deficiency with a combined TREC/KREC assay - management recommendations.

Author

Trück J, Prader S, Natalucci G, Hagmann C, Brotschi B, Kelly J, Bassler D, Steindl K, Rauch A, Baumgartner M, Fingerhut R, Hauri-Hohl M, Güngör T, Pachlopnik Schmid J, Berger C, and Reichenbach J

Subjects
B-Lymphocytes, Humans, Infant, Newborn, Switzerland, T-Lymphocytes, Neonatal Screening, Severe Combined Immunodeficiency diagnosis, Severe Combined Immunodeficiency genetics, Severe Combined Immunodeficiency therapy
Abstract

The recent introduction of newborn screening for severe primary T and B cell deficiencies in Switzerland allows rapid identification of patients with severe combined immunodeficiency (SCID). Outcomes for SCID are greatly improved by early diagnosis and treatment with allogeneic haematopoietic stem cell transplantation or, in selected cases, gene therapy. National centralised newborn screening is performed in Switzerland since January 2019 using a combined T cell receptor excision circles (TREC) / &kappa;-deleting recombination excision circles (KREC) assay, also revealing infants with non-SCID severe T and B cell disorders, who are often diagnosed with a substantial delay. Here, we outline the screening procedure currently performed in Switzerland and give recommendations for diagnostic evaluations and precautionary measures against infection in children with abnormal screening test results.

Published
2020
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47. Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis.

Author

Felber M, Steward CG, Kentouche K, Fasth A, Wynn RF, Zeilhofer U, Haunerdinger V, Volkmer B, Prader S, Gruhn B, Ehl S, Lehmberg K, Müller D, Gennery AR, Albert MH, Hauck F, Rao K, Veys P, Hassan M, Lankester AC, Schmid JP, Hauri-Hohl MM, and Güngör T

Subjects
Animals, Busulfan, Humans, Neoplasm Recurrence, Local, Rabbits, Transplantation Conditioning, Hematopoietic Stem Cell Transplantation, Lymphohistiocytosis, Hemophagocytic therapy
Abstract

Reduced-intensity/reduced-toxicity conditioning and allogeneic T-cell replete hematopoietic stem cell transplantation are curative in patients with hemophagocytic lymphohistiocytosis (HLH). Unstable donor chimerism (DC) and relapses are clinical challenges . We examined the effect of a reduced-intensity conditioning regimen based on targeted busulfan to enhance myeloid DC in HLH. The European Society for Bone and Marrow Transplantation-approved reduced-intensity conditioning protocol comprised targeted submyeloablative IV busulfan, IV fludarabine, and serotherapy comprising IV alemtuzumab (0.5-0.8 mg/kg) for unrelated-donor and IV rabbit anti-T-cell globulin for related-donor transplants. We assessed toxicity, engraftment, graft-versus-host disease (GHVD), DC in blood cell subtypes, and overall survival/event-free survival. Twenty-five patients from 7 centers were treated (median age, 0.68 year). The median total dose and cumulative area under the curve of busulfan was 13.1 mg/kg (6.4-26.4) and 63.1 mg/L × h (48-77), respectively. Bone marrow, peripheral blood stem cell, or cord blood transplants from HLA-matched related (n = 7) or unrelated (n = 18) donors were administered. Donor cells engrafted in all patients (median: neutrophils d+20/platelets d+28). At last follow-up (median, 36 months; range, 8-111 months), the median DC of CD15+ neutrophils, CD3+ T cells, and CD16+56+ natural killer cells was 99.5% (10-100), 97% (30-100), and 97.5% (30-100), respectively. Eight patients (32%) developed sinusoidal obstruction syndrome, resolving after defibrotide treatment. The 3-year overall survival and event-free survival rates were both 100%. None of the patients developed acute grade III to IV GHVD. Limited chronic GVHD was encountered in 4%. This regimen achieves excellent results with stable DC in patients with HLH., (© 2020 by The American Society of Hematology.)

Published
2020
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48. Dataset on patients with Recurrent Borderline Ovarian Tumors and Table with Review of Literature on Fertility and Oncologic Outcomes of patients with Borderline Ovarian Tumors.

Author

Plett H, Ricciardi E, Harter P, Ataseven B, Heitz F, Prader S, Schneider S, Heikaus S, Fisseler-Eckhoff A, Kommoss F, Lax SF, Staebler A, Traut A, and du Bois A

Abstract

The data presented here is related to the research article entitled "FERTILITY-SPARING SURGERY AND REPRODUCTIVE-OUTCOMES IN PATIENTS WITH BORDERLINE OVARIAN TUMORS" by Plett et al. in Journal of Gynecologic Oncology [1] and is analysed and discussed in detail. 18 Patients with Recurrent Borderline Ovarian Tumors (BOT) were identified and listed in Table 1. All patients underwent treatment for primary BOT either per radical surgery (RS) or fertility sparing surgery (FSS) by the same team in Horst Schmidt Klinik (HSK) in Wiesbaden and the Department of Gynecology and Gynecologic Oncology at Kliniken Essen-Mitte between January 2000 and December 2018 and were followed up closely. Details on patients` and surgical characteristics are given as well as management of character of recurrent disease. In Table 2 important publications from the last 20 years are listed in order to visualize better the oncologic outcomes (invasive and non-invasive relapses) and calculated risks of recurrence with the purpose to understand better the important findings of the related article cited above., (© 2020 The Authors.)

Published
2020
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49. Dilution of Molecular-Pathologic Gene Signatures by Medically Associated Factors Might Prevent Prediction of Resection Status After Debulking Surgery in Patients With Advanced Ovarian Cancer.

Author

Heitz F, Kommoss S, Tourani R, Grandelis A, Uppendahl L, Aliferis C, Burges A, Wang C, Canzler U, Wang J, Belau A, Prader S, Hanker L, Ma S, Ataseven B, Hilpert F, Schneider S, Sehouli J, Kimmig R, Kurzeder C, Schmalfeldt B, Braicu EI, Harter P, Dowdy SC, Winterhoff BJ, Pfisterer J, and du Bois A

Subjects
Biomarkers, Cytoreduction Surgical Procedures, Female, Humans, Neoplasm Staging, Carcinoma, Ovarian Epithelial, Ovarian Neoplasms
Abstract

Purpose: Predicting surgical outcome could improve individualizing treatment strategies for patients with advanced ovarian cancer. It has been suggested earlier that gene expression signatures (GES) might harbor the potential to predict surgical outcome., Experimental Design: Data derived from high-grade serous tumor tissue of FIGO stage IIIC/IV patients of AGO-OVAR11 trial were used to generate a transcriptome profiling. Previously identified molecular signatures were tested. A theoretical model was implemented to evaluate the impact of medically associated factors for residual disease (RD) on the performance of GES that predicts RD status., Results: A total of 266 patients met inclusion criteria, of those, 39.1% underwent complete resection. Previously reported GES did not predict RD in this cohort. Similarly, The Cancer Genome Atlas molecular subtypes, an independent de novo signature and the total gene expression dataset using all 21,000 genes were not able to predict RD status. Medical reasons for RD were identified as potential limiting factors that impact the ability to use GES to predict RD. In a center with high complete resection rates, a GES which would perfectly predict tumor biological RD would have a performance of only AUC 0.83, due to reasons other than tumor biology., Conclusions: Previously identified GES cannot be generalized. Medically associated factors for RD may be the main obstacle to predict surgical outcome in an all-comer population of patients with advanced ovarian cancer. If biomarkers derived from tumor tissue are used to predict outcome of patients with cancer, selection bias should be focused on to prevent overestimation of the power of such a biomarker. See related commentary by Handley and Sood, p. 9 ., (©2019 American Association for Cancer Research.)

Published
2020
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