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1. Survival associated with extent of radical hysterectomy in early-stage cervical cancer: a subanalysis of the Surveillance in Cervical CANcer (SCCAN) collaborative study

Author

Bizzarri, N, Querleu, D, Dostalek, L, van Lonkhuijzen, L, Giannarelli, D, Lopez, A, Salehi, S, Ayhan, A, Kim, S, Ortiz, D, Klat, J, Landoni, F, Pareja, R, Manchanda, R, Kostun, J, Ramirez, P, Meydanli, M, Odetto, D, Laky, R, Zapardiel, I, Weinberger, V, Dos Reis, R, Pedone Anchora, L, Amaro, K, Akilli, H, Abu-Rustum, N, Salcedo-Hernandez, R, Javurkova, V, Mom, C, Scambia, G, Falconer, H, Cibula, D, Bizzarri N., Querleu D., Dostalek L., van Lonkhuijzen L. R. C. W., Giannarelli D., Lopez A., Salehi S., Ayhan A., Kim S. H., Ortiz D. I., Klat J., Landoni F., Pareja R., Manchanda R., Kostun J., Ramirez P. T., Meydanli M. M., Odetto D., Laky R., Zapardiel I., Weinberger V., Dos Reis R., Pedone Anchora L., Amaro K., Akilli H., Abu-Rustum N. R., Salcedo-Hernandez R. A., Javurkova V., Mom C. H., Scambia G., Falconer H., Cibula D., Bizzarri, N, Querleu, D, Dostalek, L, van Lonkhuijzen, L, Giannarelli, D, Lopez, A, Salehi, S, Ayhan, A, Kim, S, Ortiz, D, Klat, J, Landoni, F, Pareja, R, Manchanda, R, Kostun, J, Ramirez, P, Meydanli, M, Odetto, D, Laky, R, Zapardiel, I, Weinberger, V, Dos Reis, R, Pedone Anchora, L, Amaro, K, Akilli, H, Abu-Rustum, N, Salcedo-Hernandez, R, Javurkova, V, Mom, C, Scambia, G, Falconer, H, Cibula, D, Bizzarri N., Querleu D., Dostalek L., van Lonkhuijzen L. R. C. W., Giannarelli D., Lopez A., Salehi S., Ayhan A., Kim S. H., Ortiz D. I., Klat J., Landoni F., Pareja R., Manchanda R., Kostun J., Ramirez P. T., Meydanli M. M., Odetto D., Laky R., Zapardiel I., Weinberger V., Dos Reis R., Pedone Anchora L., Amaro K., Akilli H., Abu-Rustum N. R., Salcedo-Hernandez R. A., Javurkova V., Mom C. H., Scambia G., Falconer H., and Cibula D.

Abstract

Background: International guidelines recommend tailoring the radicality of hysterectomy according to the known preoperative tumor characteristics in patients with early-stage cervical cancer. Objective: This study aimed to assess whether increased radicality had an effect on 5-year disease-free survival in patients with early-stage cervical cancer undergoing radical hysterectomy. The secondary aims were 5-year overall survival and pattern of recurrence. Study Design: This was an international, multicenter, retrospective study from the Surveillance in Cervical CANcer (SCCAN) collaborative cohort. Patients with the International Federation of Gynecology and Obstetrics 2009 stage IB1 and IIA1 who underwent open type B/C1/C2 radical hysterectomy according to Querleu-Morrow classification between January 2007 and December 2016, who did not undergo neoadjuvant chemotherapy and who had negative lymph nodes and free surgical margins at final histology, were included. Descriptive statistics and survival analyses were performed. Patients were stratified according to pathologic tumor diameter. Propensity score match analysis was performed to balance baseline characteristics in patients undergoing nerve-sparing and non–nerve-sparing radical hysterectomy. Results: A total of 1257 patients were included. Of note, 883 patients (70.2%) underwent nerve-sparing radical hysterectomy, and 374 patients (29.8%) underwent non–nerve-sparing radical hysterectomy. Baseline differences between the study groups were found for tumor stage and diameter (higher use of non–nerve-sparing radical hysterectomy for tumors >2 cm or with vaginal involvement; P<.0001). The use of adjuvant therapy in patients undergoing nerve-sparing and non–nerve-sparing radical hysterectomy was 27.3% vs 28.6%, respectively (P=.63). Five-year disease-free survival in patients undergoing nerve-sparing vs non–nerve-sparing radical hysterectomy was 90.1% (95% confidence interval, 87.9–92.2) vs 93.8% (95% confidence in

Published
2023

2. Stratification of lymph node metastases as macrometastases, micrometastases, or isolated tumor cells has no clinical implication in patients with cervical cancer: Subgroup analysis of the SCCAN project

Author

Dostalek, L, Benesova, K, Klat, J, Kim, S, Falconer, H, Kostun, J, dos Reis, R, Zapardiel, I, Landoni, F, Ortiz, D, van Lonkhuijzen, L, Lopez, A, Odetto, D, Borcinova, M, Jarkovsky, J, Salehi, S, Nemejcova, K, Bajsova, S, Park, K, Javurkova, V, Abu-Rustum, N, Dundr, P, Cibula, D, Dostalek L., Benesova K., Klat J., Kim S. H., Falconer H., Kostun J., dos Reis R., Zapardiel I., Landoni F., Ortiz D. I., van Lonkhuijzen L. R. C. W., Lopez A., Odetto D., Borcinova M., Jarkovsky J., Salehi S., Nemejcova K., Bajsova S., Park K. J., Javurkova V., Abu-Rustum N. R., Dundr P., Cibula D., Dostalek, L, Benesova, K, Klat, J, Kim, S, Falconer, H, Kostun, J, dos Reis, R, Zapardiel, I, Landoni, F, Ortiz, D, van Lonkhuijzen, L, Lopez, A, Odetto, D, Borcinova, M, Jarkovsky, J, Salehi, S, Nemejcova, K, Bajsova, S, Park, K, Javurkova, V, Abu-Rustum, N, Dundr, P, Cibula, D, Dostalek L., Benesova K., Klat J., Kim S. H., Falconer H., Kostun J., dos Reis R., Zapardiel I., Landoni F., Ortiz D. I., van Lonkhuijzen L. R. C. W., Lopez A., Odetto D., Borcinova M., Jarkovsky J., Salehi S., Nemejcova K., Bajsova S., Park K. J., Javurkova V., Abu-Rustum N. R., Dundr P., and Cibula D.

Abstract

Background: In cervical cancer, presence of lymph-node macrometastases (MAC) is a major prognostic factor and an indication for adjuvant treatment. However, since clinical impact of micrometastases (MIC) and isolated tumor-cells (ITC) remains controversial, we sought to identify a cut-off value for the metastasis size not associated with negative prognosis. Methods: We analyzed data from 967 cervical cancer patients (T1a1L1-T2b) registered in the SCCAN (Surveillance in Cervical CANcer) database, who underwent primary surgical treatment, including sentinel lymph-node (SLN) biopsy with pathological ultrastaging. The size of SLN metastasis was considered a continuous variable and multiple testing was performed for cut-off values of 0.01-1.0 mm. Disease-free survival (DFS) was compared between N0 and subgroups of N1 patients defined by cut-off ranges. Results: LN metastases were found in 172 (18%) patients, classified as MAC, MIC, and ITC in 79, 54, and 39 patients, respectively. DFS was shorter in patients with MAC (HR 2.20, P = 0.003) and MIC (HR 2.87, P < 0.001), while not differing between MAC/MIC (P = 0.484). DFS in the ITC subgroup was neither different from N0 (P = 0.127) nor from MIC/MAC subgroups (P = 0.449). Cut-off analysis revealed significantly shorter DFS compared to N0 in all subgroups with metastases ≥0.4 mm (HR 2.311, P = 0.04). The significance of metastases <0.4 mm could not be assessed due to limited statistical power (<80%). We did not identify any cut-off for the size of metastasis with significantly better prognosis than the rest of N1 group. Conclusions: In cervical cancer patients, the presence of LN metastases ≥0.4 mm was associated with a significant negative impact on DFS and no cut-off value for the size of metastasis with better prognosis than N1 was found. Traditional metastasis stratification based on size has no clinical implication.

Published
2023

3. Association of Hospital Surgical Volume With Survival in Early-Stage Cervical Cancer Treated With Radical Hysterectomy

Author

Bizzarri, N, Dostalek, L, Van Lonkhuijzen, L, Giannarelli, D, Lopez, A, Falconer, H, Querleu, D, Ayhan, A, Kim, S, Ortiz, D, Klat, J, Landoni, F, Rodriguez, J, Manchanda, R, Kostun, J, Ramirez, P, Meydanli, M, Odetto, D, Laky, R, Zapardiel, I, Weinberger, V, Dos Reis, R, Pedone Anchora, L, Amaro, K, Salehi, S, Akilli, H, Abu-Rustum, N, Salcedo-Hernandez, R, Javurkova, V, Mom, C, Scambia, G, Cibula, D, Bizzarri N., Dostalek L., Van Lonkhuijzen L. R. C. W., Giannarelli D., Lopez A., Falconer H., Querleu D., Ayhan A., Kim S. H., Ortiz D. I., Klat J., Landoni F., Rodriguez J., Manchanda R., Kostun J., Ramirez P. T., Meydanli M. M., Odetto D., Laky R., Zapardiel I., Weinberger V., Dos Reis R., Pedone Anchora L., Amaro K., Salehi S., Akilli H., Abu-Rustum N. R., Salcedo-Hernandez R. A., Javurkova V., Mom C. H., Scambia G., Cibula D., Bizzarri, N, Dostalek, L, Van Lonkhuijzen, L, Giannarelli, D, Lopez, A, Falconer, H, Querleu, D, Ayhan, A, Kim, S, Ortiz, D, Klat, J, Landoni, F, Rodriguez, J, Manchanda, R, Kostun, J, Ramirez, P, Meydanli, M, Odetto, D, Laky, R, Zapardiel, I, Weinberger, V, Dos Reis, R, Pedone Anchora, L, Amaro, K, Salehi, S, Akilli, H, Abu-Rustum, N, Salcedo-Hernandez, R, Javurkova, V, Mom, C, Scambia, G, Cibula, D, Bizzarri N., Dostalek L., Van Lonkhuijzen L. R. C. W., Giannarelli D., Lopez A., Falconer H., Querleu D., Ayhan A., Kim S. H., Ortiz D. I., Klat J., Landoni F., Rodriguez J., Manchanda R., Kostun J., Ramirez P. T., Meydanli M. M., Odetto D., Laky R., Zapardiel I., Weinberger V., Dos Reis R., Pedone Anchora L., Amaro K., Salehi S., Akilli H., Abu-Rustum N. R., Salcedo-Hernandez R. A., Javurkova V., Mom C. H., Scambia G., and Cibula D.

Abstract

OBJECTIVE: To evaluate the association of number of radical hysterectomies performed per year in each center with disease-free survival and overall survival. METHODS: We conducted an international, multicenter, retrospective study of patients previously included in the Surveillance in Cervical Cancer collaborative studies. Individuals with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB1-IIA1 cervical cancer who underwent radical hysterectomy and had negative lymph nodes at final histology were included. Patients were treated at referral centers for gynecologic oncology according to updated national and international guidelines. Optimal cutoffs for surgical volume were identified using an unadjusted Cox proportional hazard model, with disease-free survival as the outcome and defined as the value that minimizes the P-value of the split in groups in terms of disease-free survival. Propensity score matching was used to create statistically similar cohorts at baseline. RESULTS: A total of 2,157 patients were initially included. The two most significant cutoffs for surgical volume were identified at seven and 17 surgical procedures, dividing the entire cohort into low-volume, middle-volume, and high-volume centers. After propensity score matching, 1,238 patients were analyzed - 619 (50.0%) in the high-volume group, 523 (42.2%) in the middle-volume group, and 96 (7.8%) in the low-volume group. Patients who underwent surgery in higher-volume institutions had progressively better 5-year disease-free survival than those who underwent surgery in lower-volume centers (92.3% vs 88.9% vs 83.8%, P=.029). No difference was noted in 5-year overall survival (95.9% vs 97.2% vs 95.2%, P=.70). Cox multivariable regression analysis showed that FIGO stage greater than IB1, presence of lymphovascular space invasion, grade greater than 1, tumor diameter greater than 20 mm, minimally invasive surgical approach, nonsquamous cell carcinoma histology, and lower-volum

Published
2023

6. The annual recurrence risk model for tailored surveillance strategy in patients with cervical cancer

Author

Cibula, D, Dostalek, L, Jarkovsky, J, Mom, C, Lopez, A, Falconer, H, Fagotti, A, Ayhan, A, Kim, S, Isla Ortiz, D, Klat, J, Obermair, A, Landoni, F, Rodriguez, J, Manchanda, R, Kostun, J, dos Reis, R, Meydanli, M, Odetto, D, Laky, R, Zapardiel, I, Weinberger, V, Benesova, K, Borcinova, M, Pari, D, Salehi, S, Bizzarri, N, Akilli, H, Abu-Rustum, N, Salcedo-Hernandez, R, Javurkova, V, Slama, J, van Lonkhuijzen, L, Cibula D., Dostalek L., Jarkovsky J., Mom C. H., Lopez A., Falconer H., Fagotti A., Ayhan A., Kim S. H., Isla Ortiz D., Klat J., Obermair A., Landoni F., Rodriguez J., Manchanda R., Kostun J., dos Reis R., Meydanli M. M., Odetto D., Laky R., Zapardiel I., Weinberger V., Benesova K., Borcinova M., Pari D., Salehi S., Bizzarri N., Akilli H., Abu-Rustum N. R., Salcedo-Hernandez R. A., Javurkova V., Slama J., van Lonkhuijzen L. R. C. W., Cibula, D, Dostalek, L, Jarkovsky, J, Mom, C, Lopez, A, Falconer, H, Fagotti, A, Ayhan, A, Kim, S, Isla Ortiz, D, Klat, J, Obermair, A, Landoni, F, Rodriguez, J, Manchanda, R, Kostun, J, dos Reis, R, Meydanli, M, Odetto, D, Laky, R, Zapardiel, I, Weinberger, V, Benesova, K, Borcinova, M, Pari, D, Salehi, S, Bizzarri, N, Akilli, H, Abu-Rustum, N, Salcedo-Hernandez, R, Javurkova, V, Slama, J, van Lonkhuijzen, L, Cibula D., Dostalek L., Jarkovsky J., Mom C. H., Lopez A., Falconer H., Fagotti A., Ayhan A., Kim S. H., Isla Ortiz D., Klat J., Obermair A., Landoni F., Rodriguez J., Manchanda R., Kostun J., dos Reis R., Meydanli M. M., Odetto D., Laky R., Zapardiel I., Weinberger V., Benesova K., Borcinova M., Pari D., Salehi S., Bizzarri N., Akilli H., Abu-Rustum N. R., Salcedo-Hernandez R. A., Javurkova V., Slama J., and van Lonkhuijzen L. R. C. W.

Abstract

Purpose: Current guidelines for surveillance strategy in cervical cancer are rigid, recommending the same strategy for all survivors. The aim of this study was to develop a robust model allowing for individualised surveillance based on a patient's risk profile. Methods: Data of 4343 early-stage patients with cervical cancer treated between 2007 and 2016 were obtained from the international SCCAN (Surveillance in Cervical Cancer) consortium. The Cox proportional hazards model predicting disease-free survival (DFS) was developed and internally validated. The risk score, derived from regression coefficients of the model, stratified the cohort into significantly distinctive risk groups. On its basis, the annual recurrence risk model (ARRM) was calculated. Results: Five variables were included in the prognostic model: maximal pathologic tumour diameter; tumour histotype; grade; number of positive pelvic lymph nodes; and lymphovascular space invasion. Five risk groups significantly differing in prognosis were identified with a five-year DFS of 97.5%, 94.7%, 85.2% and 63.3% in increasing risk groups, whereas a two-year DFS in the highest risk group equalled 15.4%. Based on the ARRM, the annual recurrence risk in the lowest risk group was below 1% since the beginning of follow-up and declined below 1% at years three, four and >5 in the medium-risk groups. In the whole cohort, 26% of recurrences appeared at the first year of the follow-up, 48% by year two and 78% by year five. Conclusion: The ARRM represents a potent tool for tailoring the surveillance strategy in early-stage patients with cervical cancer based on the patient's risk status and respective annual recurrence risk. It can easily be used in routine clinical settings internationally.

Published
2021

7. 12P Any size of lymph node metastasis should be considered N1 in patients with cervical cancer

Author

Cibula, D., primary, Benešová, K., additional, Klát, J., additional, Falconer, H., additional, Kim, S., additional, Van Lonkhuijzen, L., additional, Lopez, A., additional, Isla, D., additional, Landoni, F., additional, Kostun, J., additional, Dos Reis, R., additional, Odetto, D., additional, Zapardiel, I., additional, Borčinová, M., additional, Jarkovský, J., additional, Javůrková, V., additional, Salehi, S., additional, Abu-Rustum, N., additional, and Dostálek, L., additional

Published
2022
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8. 942 Survival after recurrence in early-stage cervical cancer patients

Author

Van Lonkhuijzen, L, primary, Dostalek, L, additional, Jarkovsky, J, additional, Lopez, A, additional, Falconer, H, additional, Scambia, G, additional, Ayhan, A, additional, Kim, S, additional, Isla Ortiz, D, additional, Klat, J, additional, Obermair, A, additional, Martino, GDI, additional, Pareja, R, additional, Manchanda, R, additional, Kostun, J, additional, Dos Reis, R, additional, Zapardiel, I, additional, Weinberger, V, additional, and Cibula, D, additional

Published
2021
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9. 960 The annual recurrence risk model for tailored surveillance strategy in cervical cancer patients

Author

Cibula, D, primary, Jarkovsky, J, additional, Van Lonkhuijzen, L, additional, Falconer, H, additional, Fagotti, A, additional, Ayhan, A, additional, Kim, S, additional, Isla Ortiz, D, additional, Klat, J, additional, Obermair, A, additional, Landoni, F, additional, Rodriguez, J, additional, Manchanda, R, additional, Kostun, J, additional, Dos Reis, R, additional, Meydanli, MM, additional, Odetto, D, additional, Laky, R, additional, Borčinová, M, additional, and Lopez, A, additional

Published
2021
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10. 898 The impact of micrometastases in cervical cancer patients – a retrospective study of the SCCAN (Surveillance in Cervical CANcer) project

Author

Dostalek, L, primary, Borcinova, M, additional, Benesova, K, additional, Klat, J, additional, Falconer, H, additional, Kim, SH, additional, Van Lonkhuijzen, LR, additional, Lopez, A, additional, Isla Ortiz, D, additional, Landoni, F, additional, Kostun, J, additional, Dos Reis, R, additional, Odetto, D, additional, Zapardiel, I, additional, Jarkovsky, J, additional, Javukova, V, additional, Salehi, S, additional, Abu-Rustum, NR, additional, Graf, P, additional, and Cibula, D, additional

Published
2021
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11. SURVIVAL AFTER RECURRENCE IN EARLY-STAGE CERVICAL CANCER PATIENTS

Author

Van Lonkhuijzen, L., Dostalek, L., Jarkovsky, J., Lopez, A., Falconer, H., Scambia, G., Ayhan, A., Kim, S., Isla Ortiz, D., Klat, J., Obermair, A., Martino, Gdi, Pareja, R., Manchanda, R., Kostun, J., Dos Reis, R., Zapardiel, I., Weinberger, V., Cibula, D., Obstetrics and Gynaecology, and CCA - Cancer Treatment and Quality of Life

Published
2021

12. THE IMPACT OF MICROMETASTASES IN CERVICAL CANCER PATIENTS - A RETROSPECTIVE STUDY OF THE SCCAN (SURVEILLANCE IN CERVICAL CANCER) PROJECT

Author

Dostalek, L., Borcinova, M., Benesova, K., Klat, J., Falconer, H., Kim, S. H., Van Lonkhuijzen, L. R., Lopez, A., Isla Ortiz, D., Landoni, F., Kostun, J., Dos Reis, R., Odetto, D., Zapardiel, I., Jarkovsky, J., Javukova, V., Salehi, S., Abu-Rustum, N. R., Graf, P., Cibula, D., Obstetrics and Gynaecology, and CCA - Cancer Treatment and Quality of Life

Published
2021

13. The annual recurrence risk model for tailored surveillance strategy in patients with cervical cancer

Author

Cibula, D., Dostalek, L., Jarkovsky, J., Mom, C. H., Lopez, A., Falconer, H., Fagotti, Anna, Ayhan, A., Kim, S. H., Isla Ortiz, D., Klat, J., Obermair, A., Landoni, F., Rodriguez, J., Manchanda, R., Kostun, J., dos Reis, R., Meydanli, M. M., Odetto, D., Laky, R., Zapardiel, I., Weinberger, V., Benesova, K., Borcinova, M., Pari, D., Salehi, S., Bizzarri, N., Akilli, H., Abu-Rustum, N. R., Salcedo-Hernandez, R. A., Javurkova, V., Slama, J., van Lonkhuijzen, L. R. C. W., Fagotti A. (ORCID:0000-0001-5579-335X), Cibula, D., Dostalek, L., Jarkovsky, J., Mom, C. H., Lopez, A., Falconer, H., Fagotti, Anna, Ayhan, A., Kim, S. H., Isla Ortiz, D., Klat, J., Obermair, A., Landoni, F., Rodriguez, J., Manchanda, R., Kostun, J., dos Reis, R., Meydanli, M. M., Odetto, D., Laky, R., Zapardiel, I., Weinberger, V., Benesova, K., Borcinova, M., Pari, D., Salehi, S., Bizzarri, N., Akilli, H., Abu-Rustum, N. R., Salcedo-Hernandez, R. A., Javurkova, V., Slama, J., van Lonkhuijzen, L. R. C. W., and Fagotti A. (ORCID:0000-0001-5579-335X)

Abstract

Purpose: Current guidelines for surveillance strategy in cervical cancer are rigid, recommending the same strategy for all survivors. The aim of this study was to develop a robust model allowing for individualised surveillance based on a patient's risk profile. Methods: Data of 4343 early-stage patients with cervical cancer treated between 2007 and 2016 were obtained from the international SCCAN (Surveillance in Cervical Cancer) consortium. The Cox proportional hazards model predicting disease-free survival (DFS) was developed and internally validated. The risk score, derived from regression coefficients of the model, stratified the cohort into significantly distinctive risk groups. On its basis, the annual recurrence risk model (ARRM) was calculated. Results: Five variables were included in the prognostic model: maximal pathologic tumour diameter; tumour histotype; grade; number of positive pelvic lymph nodes; and lymphovascular space invasion. Five risk groups significantly differing in prognosis were identified with a five-year DFS of 97.5%, 94.7%, 85.2% and 63.3% in increasing risk groups, whereas a two-year DFS in the highest risk group equalled 15.4%. Based on the ARRM, the annual recurrence risk in the lowest risk group was below 1% since the beginning of follow-up and declined below 1% at years three, four and >5 in the medium-risk groups. In the whole cohort, 26% of recurrences appeared at the first year of the follow-up, 48% by year two and 78% by year five. Conclusion: The ARRM represents a potent tool for tailoring the surveillance strategy in early-stage patients with cervical cancer based on the patient's risk status and respective annual recurrence risk. It can easily be used in routine clinical settings internationally.

Published
2021

14. EP265 The role of methylation silencing of tumor suppressor genes in cervical HSIL: a prospective cytologic-histologic correlation study of 70 cases

Author

Ondic, O, primary, Bouda, J, additional, Nemcova, J, additional, Kinkorova-Lunackova, I, additional, Chytra, J, additional, Presl, J, additional, Alaghehbandan, R, additional, Cerna, K, additional, Gomolcakova, B, additional, Kostun, J, additional, Sidlova, H, additional, Vlasak, P, additional, and Majek, O, additional

Published
2019
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20. Stratification of lymph node metastases as macrometastases, micrometastases, or isolated tumor cells has no clinical implication in patients with cervical cancer: Subgroup analysis of the SCCAN project

Author

Dostálek, Lukáš, Benešová, Klára, Klát, Jaroslav, Kim, Sarah H., Falconer, Henrik, Kostun, Jan, dos Reis, Ricardo, Zapardiel, Ignacio, Landoni, Fabio, Ortiz, David Isla, van Lonkhuijzen, Luc R. C. W., Lopez, Aldo, Odetto, Diego, Borčinová, Martina, Jarkovsky, Jiri, Salehi, Sahar, Němejcová, Kristýna, Bajsová, Sylva, Park, Kay J., Javůrková, Veronika, Abu-Rustum, Nadeem R., Dundr, Pavel, Cibula, David, Dostalek, L, Benesova, K, Klat, J, Kim, S, Falconer, H, Kostun, J, dos Reis, R, Zapardiel, I, Landoni, F, Ortiz, D, van Lonkhuijzen, L, Lopez, A, Odetto, D, Borcinova, M, Jarkovsky, J, Salehi, S, Nemejcova, K, Bajsova, S, Park, K, Javurkova, V, Abu-Rustum, N, Dundr, P, Cibula, D, Obstetrics and Gynaecology, and CCA - Cancer Treatment and Quality of Life

Subjects
History, Low volume metastasis, Macrometastasi, Polymers and Plastics, Prognosi, Disease-free survival, Isolated tumor cells, Macrometastasis, Obstetrics and Gynecology, Isolated tumor cell, Classification, Prognosis, Industrial and Manufacturing Engineering, Low volume metastasi, Micrometastasis, Micrometastasi, Oncology, Cervical cancer, Histopathological ultrastaging, Business and International Management, Sentinel lymph node
Abstract

Background: In cervical cancer, presence of lymph-node macrometastases (MAC) is a major prognostic factor and an indication for adjuvant treatment. However, since clinical impact of micrometastases (MIC) and isolated tumor-cells (ITC) remains controversial, we sought to identify a cut-off value for the metastasis size not associated with negative prognosis. Methods: We analyzed data from 967 cervical cancer patients (T1a1L1-T2b) registered in the SCCAN (Surveillance in Cervical CANcer) database, who underwent primary surgical treatment, including sentinel lymph-node (SLN) biopsy with pathological ultrastaging. The size of SLN metastasis was considered a continuous variable and multiple testing was performed for cut-off values of 0.01-1.0 mm. Disease-free survival (DFS) was compared between N0 and subgroups of N1 patients defined by cut-off ranges. Results: LN metastases were found in 172 (18%) patients, classified as MAC, MIC, and ITC in 79, 54, and 39 patients, respectively. DFS was shorter in patients with MAC (HR 2.20, P = 0.003) and MIC (HR 2.87, P < 0.001), while not differing between MAC/MIC (P = 0.484). DFS in the ITC subgroup was neither different from N0 (P = 0.127) nor from MIC/MAC subgroups (P = 0.449). Cut-off analysis revealed significantly shorter DFS compared to N0 in all subgroups with metastases ≥0.4 mm (HR 2.311, P = 0.04). The significance of metastases

Published
2023
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21. Association of Hospital Surgical Volume With Survival in Early-Stage Cervical Cancer Treated With Radical Hysterectomy

Author

Bizzarri, Nicolò, Dostálek, Lukáš, van Lonkhuijzen, Luc R. C. W., Giannarelli, Diana, Lopez, Aldo, Falconer, Henrik, Querleu, Denis, Ayhan, Ali, Kim, Sarah H., Ortiz, David Isla, Klat, Jaroslav, Landoni, Fabio, Rodriguez, Juliana, Manchanda, Ranjit, Kosťun, Jan, Ramirez, Pedro T., Meydanli, Mehmet M., Odetto, Diego, Laky, Rene, Zapardiel, Ignacio, Weinberger, Vit, Dos Reis, Ricardo, Pedone Anchora, Luigi, Amaro, Karina, Salehi, Sahar, Akilli, Huseyin, Abu-Rustum, Nadeem R., Salcedo-Hernández, Rosa A., Javůrková, Veronika, Mom, Constantijne H., Scambia, Giovanni, Cibula, David, Obstetrics and Gynaecology, CCA - Cancer Treatment and Quality of Life, Bizzarri, N, Dostalek, L, Van Lonkhuijzen, L, Giannarelli, D, Lopez, A, Falconer, H, Querleu, D, Ayhan, A, Kim, S, Ortiz, D, Klat, J, Landoni, F, Rodriguez, J, Manchanda, R, Kostun, J, Ramirez, P, Meydanli, M, Odetto, D, Laky, R, Zapardiel, I, Weinberger, V, Dos Reis, R, Pedone Anchora, L, Amaro, K, Salehi, S, Akilli, H, Abu-Rustum, N, Salcedo-Hernandez, R, Javurkova, V, Mom, C, Scambia, G, Cibula, D, Obstetrics and gynaecology, CCA - Cancer Treatment and quality of life, CCA - Cancer biology and immunology, and Amsterdam Reproduction & Development (AR&D)

Subjects
Settore MED/40 - GINECOLOGIA E OSTETRICIA, Radical Hysterectomy, Obstetrics and Gynecology, Cervical Cancer, Hospital Surgical Volume, Surgery and Survival in Early-Stage Cervical Cancer
Abstract

OBJECTIVE: To evaluate the association of number of radical hysterectomies performed per year in each center with disease-free survival and overall survival. METHODS: We conducted an international, multicenter, retrospective study of patients previously included in the Surveillance in Cervical Cancer collaborative studies. Individuals with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB1-IIA1 cervical cancer who underwent radical hysterectomy and had negative lymph nodes at final histology were included. Patients were treated at referral centers for gynecologic oncology according to updated national and international guidelines. Optimal cutoffs for surgical volume were identified using an unadjusted Cox proportional hazard model, with disease-free survival as the outcome and defined as the value that minimizes the P-value of the split in groups in terms of disease-free survival. Propensity score matching was used to create statistically similar cohorts at baseline. RESULTS: A total of 2,157 patients were initially included. The two most significant cutoffs for surgical volume were identified at seven and 17 surgical procedures, dividing the entire cohort into low-volume, middle-volume, and high-volume centers. After propensity score matching, 1,238 patients were analyzed - 619 (50.0%) in the high-volume group, 523 (42.2%) in the middle-volume group, and 96 (7.8%) in the low-volume group. Patients who underwent surgery in higher-volume institutions had progressively better 5-year disease-free survival than those who underwent surgery in lower-volume centers (92.3% vs 88.9% vs 83.8%, P=.029). No difference was noted in 5-year overall survival (95.9% vs 97.2% vs 95.2%, P=.70). Cox multivariable regression analysis showed that FIGO stage greater than IB1, presence of lymphovascular space invasion, grade greater than 1, tumor diameter greater than 20 mm, minimally invasive surgical approach, nonsquamous cell carcinoma histology, and lower-volume centers represented independent risk factors for recurrence. CONCLUSION: Surgical volume of centers represented an independent prognostic factor affecting disease-free survival. Increasing number of radical hysterectomies performed in each center every year was associated with improved disease-free survival.

Published
2023
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22. The annual recurrence risk model for tailored surveillance strategy in patients with cervical cancer

Author

Jaroslav Klat, Darwin Pari, Luc R.C.W. van Lonkhuijzen, Klára Benešová, Nicolò Bizzarri, Ignacio Zapardiel, Nadeem R. Abu-Rustum, Aldo Lopez, Jiří Sláma, Andreas Obermair, Fabio Landoni, Mehmet Mutlu Meydanli, Anna Fagotti, Diego Odetto, Veronika Javůrková, Sarah H. Kim, Vít Weinberger, Rosa A. Salcedo-Hernández, Jiri Jarkovsky, Henrik Falconer, Ali Ayhan, Jan Kosťun, David Cibula, L Dostalek, Constantijne H. Mom, Sahar Salehi, Juliana Rodriguez, Ranjit Manchanda, Martina Borčinová, Ricardo dos Reis, David Isla Ortiz, Rene Laky, Huseyin Akilli, Obstetrics and Gynaecology, CCA - Cancer Treatment and Quality of Life, Cibula, D, Dostalek, L, Jarkovsky, J, Mom, C, Lopez, A, Falconer, H, Fagotti, A, Ayhan, A, Kim, S, Isla Ortiz, D, Klat, J, Obermair, A, Landoni, F, Rodriguez, J, Manchanda, R, Kostun, J, dos Reis, R, Meydanli, M, Odetto, D, Laky, R, Zapardiel, I, Weinberger, V, Benesova, K, Borcinova, M, Pari, D, Salehi, S, Bizzarri, N, Akilli, H, Abu-Rustum, N, Salcedo-Hernandez, R, Javurkova, V, Slama, J, van Lonkhuijzen, L, Amsterdam Reproduction & Development (AR&D), CCA - Cancer Treatment and quality of life, and Obstetrics and gynaecology

Subjects
Cancer Research, medicine.medical_specialty, Article, Recurrence risk, 03 medical and health sciences, 0302 clinical medicine, Risk groups, Internal medicine, Medicine, In patient, Cervical cancer, 030219 obstetrics & reproductive medicine, Framingham Risk Score, Surveillance, business.industry, Proportional hazards model, medicine.disease, 3. Good health, Settore MED/40 - GINECOLOGIA E OSTETRICIA, Oncology, 030220 oncology & carcinogenesis, Annual recurrence risk, Cohort, Prognostic model, business
Abstract

Purpose Current guidelines for surveillance strategy in cervical cancer are rigid, recommending the same strategy for all survivors. The aim of this study was to develop a robust model allowing for individualised surveillance based on a patient's risk profile. Methods Data of 4343 early-stage patients with cervical cancer treated between 2007 and 2016 were obtained from the international SCCAN (Surveillance in Cervical Cancer) consortium. The Cox proportional hazards model predicting disease-free survival (DFS) was developed and internally validated. The risk score, derived from regression coefficients of the model, stratified the cohort into significantly distinctive risk groups. On its basis, the annual recurrence risk model (ARRM) was calculated. Results Five variables were included in the prognostic model: maximal pathologic tumour diameter; tumour histotype; grade; number of positive pelvic lymph nodes; and lymphovascular space invasion. Five risk groups significantly differing in prognosis were identified with a five-year DFS of 97.5%, 94.7%, 85.2% and 63.3% in increasing risk groups, whereas a two-year DFS in the highest risk group equalled 15.4%. Based on the ARRM, the annual recurrence risk in the lowest risk group was below 1% since the beginning of follow-up and declined below 1% at years three, four and >5 in the medium-risk groups. In the whole cohort, 26% of recurrences appeared at the first year of the follow-up, 48% by year two and 78% by year five. Conclusion The ARRM represents a potent tool for tailoring the surveillance strategy in early-stage patients with cervical cancer based on the patient's risk status and respective annual recurrence risk. It can easily be used in routine clinical settings internationally.

Published
2021
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23. The Role of HE4 in the Follow-Up of Advanced Ovarian, Fallopian Tube, and Primary Peritoneal Cancer-CEEGOG OX-01 Study.

Author

Presl J, Havelka P, Weinberger V, Ovesna P, Fekete P, Fruhauf F, Jedryka M, Bystricky B, Strojna A, Volodko N, Matylevich O, Herboltova P, Blecharz P, Kalist V, Ehrlichova L, Stranik P, Masak L, Poncova R, Czekanski A, Chaloupkova B, Koblizkova M, Smoligova V, Hrabalova M, Jaksicova A, Linkesch P, Viktora L, Bouda J, Vlasak P, and Kostun J

Abstract

Background : Ovarian, fallopian tube, and primary peritoneal cancers often share clinical characteristics and are typically diagnosed at advanced stages due to nonspecific symptoms. The utility of tumor markers, particularly CA125 and HE4, in the diagnosis and follow-up of these cancers remains an area of active investigation. Objectives : The CEEGOG (Central and Eastern European Gynecologic Oncology Group) OX-01 study aimed to evaluate HE4's role alongside CA125 in follow-up for advanced-stage ovarian, fallopian tube, and primary peritoneal cancers. It assessed the potential for detecting recurrence using marker elevation and imaging methods, examining the necessity of dynamic monitoring and current cut-off values' accuracy for early relapse detection. Methods : In this multicenter prospective cohort study, 117 eligible patients with Stage III-IV cancers were included. Patients had elevated CA125 or HE4 at diagnosis and achieved complete remission after first-line treatment. HE4 and CA125 levels were monitored every 3-4 months in the first two years and every six months thereafter. CT scans were performed if markers exceeded set thresholds or increased by over 20%. Results : During a median follow-up of 13.7 months, 73% of patients relapsed. Median HE4 levels were significantly higher in relapsed patients. A 10 IU/mL increase from baseline in CA125 had a sensitivity of 83% and specificity of 93%, while a 15 pmol/L increase in HE4 had a sensitivity of 74% and specificity of 92% for predicting relapse up to three months before CT scan detection. Conclusions : The study found that dynamic changes in HE4 and CA125 levels, rather than predefined cut-off values, are crucial for early relapse detection. These markers may offer a significant lead time over imaging, potentially enabling earlier intervention. Further research is needed to validate these findings.

Published
2024
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24. Diagnostic Reliability, Accuracy and Safety of Ultrasound-guided Biopsy and Ascites Puncture in Primarily Inoperable Ovarian Tumours.

Author

Vlasak P, Bouda J, Kostun J, Berezovskiy D, Zikan M, Weinberger V, Ondic O, Rusavy Z, Kucera R, Topolcan O, Novotny Z, and Presl J

Subjects
Ascites pathology, Cytodiagnosis, Female, Histocytochemistry, Humans, Reproducibility of Results, Retrospective Studies, Image-Guided Biopsy methods, Image-Guided Biopsy standards, Ovarian Neoplasms diagnosis, Punctures methods, Ultrasonography methods
Abstract

Background/aim: To compare the diagnostic reliability, accuracy and safety of ultrasound-guided biopsy (Tru-Cut biopsy) and ascites puncture in patients with a primarily inoperable malignant ovarian tumor., Patients and Methods: This is a retrospective analysis of the studied methods in consecutively examined patients and a prospective validation of these methods. 79 women with a suspected primarily inoperable ovarian tumor underwent Tru-Cut biopsies and were included in the ultrasound-guided biopsy group. In addition, 55 patients after ascites puncture were enrolled in the comparison group. Both procedures were performed in 48 patients for the prospective validation., Results: Significant differences in favour of ultrasound-guided biopsy were found in all studied variables (malignancy confirmation 72.9% vs. 95.8%, tumor origin 52.1% vs. 89.6%, histologic subtype 43.8% vs. 85.4% and accuracy, i.e. agreement of preoperative and definitive diagnosis 43.7% vs. 95.4%)., Conclusion: Ultrasound-guided biopsy is an accurate, reliable, safe and minimally invasive method. Owing to the high reliability and accuracy, it has the capacity to replace ascites puncture with cytologic examination or a more invasive method (laparoscopy, laparotomy) for adequate tumor sampling., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Published
2020
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25. Calreticulin exposure correlates with robust adaptive antitumor immunity and favorable prognosis in ovarian carcinoma patients.

Author

Kasikova L, Hensler M, Truxova I, Skapa P, Laco J, Belicova L, Praznovec I, Vosahlikova S, Halaska MJ, Brtnicky T, Rob L, Presl J, Kostun J, Cremer I, Ryska A, Kroemer G, Galluzzi L, Spisek R, and Fucikova J

Subjects
Adult, Aged, Aged, 80 and over, Endoplasmic Reticulum Stress, Female, Humans, Middle Aged, Ovarian Neoplasms genetics, Prognosis, RNA-Seq, Tumor Microenvironment genetics, Tumor Microenvironment immunology, Calreticulin immunology, Ovarian Neoplasms immunology
Abstract

Background: Adjuvanticity, which is the ability of neoplastic cells to deliver danger signals, is critical for the host immune system to mount spontaneous and therapy-driven anticancer immune responses. One of such signals, i.e., the exposure of calreticulin (CALR) on the membrane of malignant cells experiencing endoplasmic reticulum (ER) stress, is well known for its role in the activation of immune responses to dying cancer cells. However, the potential impact of CALR on the immune contexture of primary and metastatic high-grade serous carcinomas (HGSCs) and its prognostic value for patients with HGSC remains unclear., Method: We harnessed a retrospective cohort of primary (no = 152) and metastatic (no = 74) tumor samples from HGSC patients to investigate the CALR expression in relation with prognosis and function orientation of the tumor microenvironment. IHC data were complemented with transcriptomic and functional studies on second prospective cohort of freshly resected HGSC samples. In silico analysis of publicly available RNA expression data from 302 HGSC samples was used as a confirmatory approach., Results: We demonstrate that CALR exposure on the surface of primary and metastatic HGSC cells is driven by a chemotherapy-independent ER stress response and culminates with the establishment of a local immune contexture characterized by T H 1 polarization and cytotoxic activity that enables superior clinical benefits., Conclusions: Our data indicate that CALR levels in primary and metastatic HGSC samples have robust prognostic value linked to the activation of clinically-relevant innate and adaptive anticancer immune responses.

Published
2019
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26. CD44 as a cancer stem cell marker and its prognostic value in patients with ovarian carcinoma.

Author

Bartakova A, Michalova K, Presl J, Vlasak P, Kostun J, and Bouda J

Subjects
Adult, Aged, Aged, 80 and over, Biomarkers, Tumor analysis, Biomarkers, Tumor metabolism, Carcinoma pathology, Female, Humans, Hyaluronan Receptors metabolism, Immunohistochemistry, Middle Aged, Neoplasms, Glandular and Epithelial pathology, Ovarian Neoplasms pathology, Ovary pathology, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Regression Analysis, Retrospective Studies, Carcinoma metabolism, Hyaluronan Receptors analysis, Neoplasms, Glandular and Epithelial metabolism, Neoplastic Stem Cells metabolism, Ovarian Neoplasms metabolism
Abstract

The aim of our study was to clarify whether the CD44 adhesion molecule as a cancer stem cell marker could also serve as a prognostic factor in patients with epithelial ovarian cancer (EOC). A retrospective study was performed on 87 patients with histologically verified EOC. Specimens of both primary tumour and implantation metastases were tested from 48 of them. CD44 expression was detected by immunohistochemistry. We looked for the cut-off levels of CD44 expression using the Cox regression model. We confirmed statistically significant prognostic factors for overall survival (OS) and disease-free interval (DFI) to be: stage of the disease, postoperative residual tumour and papillary serous histological type. We demonstrated a statistically significant correlation between low CD44 expression and serous papillary carcinoma histotype, tumour recurrence and chemoresistance at a value below 2%. CD44 was neither a prognostic factor of OS nor of DFI. IMPACT STATEMENT What is already known about this subject: Epithelial ovarian cancer is the second most common gynaecological cancer in developed countries. Despite great efforts devoted to ovarian cancer research during past decades, levels of patient mortality have changed very little. Cancer stem cells (CSCs) are subpopulations of cells with typical characteristics of stem cells - i.e. the ability to self-renew and differentiate in a variety of cell types. The main surface marker typical for CSCs is CD44. The aim of our study was to clarify whether the CD44 as a CSCs marker could serve as a prognostic factor in patients with epithelial ovarian cancer. Previous studies published on this topic revealed controversial results. The novelty of our study lies in looking for the cut-off using the Cox regression model., What This Study Adds: We demonstrated a statistically significant correlation between low CD44 expression and serous papillary carcinoma histotype, tumour recurrence and chemoresistance at a value below 2%, however, CD44 was neither a prognostic factor of overall survival nor of disease-free interval. We propose to investigate other markers including other CSCs as a prognostic factors or potential aims for targeted therapy in ovarian cancer.

Published
2018
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27. Importance of Preoperative Knowledge of the Biomarker HE4 in Early-stage Endometrial Cancer Regarding Surgical Management.

Author

Presl J, Ovesna P, Novotny Z, Vlasak P, Bouda J, Kostun J, Topolcan O, Kucera R, Bednarikova M, and Weinberger V

Subjects
Aged, CA-125 Antigen blood, Endometrial Neoplasms diagnostic imaging, Endometrial Neoplasms pathology, Endometrial Neoplasms surgery, Female, Humans, Lymphatic Metastasis, Middle Aged, Neoplasm Staging, Preoperative Period, Ultrasonography, WAP Four-Disulfide Core Domain Protein 2, Biomarkers, Tumor blood, Endometrial Neoplasms blood, Proteins analysis
Abstract

Aim: To analyze the utility of HE4 assessment in preoperative management of patients with early-stage endometrial cancer for stratification into low-risk and high-risk groups., Patients and Methods: The following data were prospectively collected from patients operated for endometrial cancer from 05/2012 till 9/2016; age, HE4, CA125, expert ultrasound examination of the pelvis, histotype, grade, FIGO stage., Results: In total, 124 patients were enrolled. A cut-off of ≥113 pmol/l HE4 demonstrated 40.3% sensitivity and 83.9% specificity for detection of high-risk patients. Correlations of HE4 with age (p<0.001), depth of myometrial invasion (p=0.001), clinical stage of the disease according to ultrasound - T1a vs. T1b (63.6 pmol/l vs. 110.6 pmol/l, p<0.001) were found. However, no correlation of HE4 with lymph node invasion (p=0.07) and tumor grade (p=0.212) was identified., Conclusion: HE4 levels correspond to clinical and FIGO stage of the disease. The sensitivity and specificity does not reach the transvaginal ultrasound results in preoperative assessment of the extent of the disease. Combination of HE4 with ultrasound does not improve the stratification of patients into low-risk and high-risk groups. Preoperative assessment of HE4 is useful providing no imaging method is available., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Published
2017
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