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1. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial

Author

McCormack, M, Whitmarsh, K, Allerton, R, Gregory, D, Symonds, P, Hoskin, PJ, Adusumalli, M, Anand, A, Wade, R, Stewart, A, Taylor, W, Lutgens, LCHW, Hollema, H, Pras, E, Snyers, A, Westerveld, GH, Jobsen, JJ, Slot, A, Mens, JM, Stam, TC, Van Triest, B, Van der Steen-Banasik, EM, De Winter, KAJ, Quinn, MA, Kolodziej, I, Pyman, J, Johnson, C, Capp, A, Fossati, R, Colombo, A, Carinelli, S, Ferrero, A, Artioli, G, Davidson, C, McLachlin, CM, Ghatage, P, Rittenberg, PVC, Souhami, L, Thomas, G, Duvillard, P, Berton-Rigaud, D, Tubiana-Mathieu, N, de Boer, Stephanie M, Powell, Melanie E, Mileshkin, Linda, Katsaros, Dionyssios, Bessette, Paul, Haie-Meder, Christine, Ottevanger, Petronella B, Ledermann, Jonathan A, Khaw, Pearly, D'Amico, Romerai, Fyles, Anthony, Baron, Marie-Helene, Jürgenliemk-Schulz, Ina M, Kitchener, Henry C, Nijman, Hans W, Wilson, Godfrey, Brooks, Susan, Gribaudo, Sergio, Provencher, Diane, Hanzen, Chantal, Kruitwagen, Roy F, Smit, Vincent T H B M, Singh, Naveena, Do, Viet, Lissoni, Andrea, Nout, Remi A, Feeney, Amanda, Verhoeven-Adema, Karen W, Putter, Hein, and Creutzberg, Carien L

Published
2019
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3. Radiation Therapy Techniques and Treatment-Related Toxicity in the PORTEC-3 Trial: Comparison of 3-Dimensional Conformal Radiation Therapy Versus Intensity-Modulated Radiation Therapy

Author

Wortman, BG, Post, CCB, Powell, ME, Khaw, P, Fyles, A, D'Amico, R, Haie-Meder, C, Jurgenliemk-Schulz, IM, McCormack, M, Do, V, Katsaros, D, Bessette, P, Baron, MH, Nout, RA, Whitmarsh, K, Mileshkin, L, Lutgens, LCHW, Kitchener, HC, Brooks, S, Nijman, HW, Astreinidou, E, Putter, H, Creutzberg, CL, de Boer, SM, Wortman, BG, Post, CCB, Powell, ME, Khaw, P, Fyles, A, D'Amico, R, Haie-Meder, C, Jurgenliemk-Schulz, IM, McCormack, M, Do, V, Katsaros, D, Bessette, P, Baron, MH, Nout, RA, Whitmarsh, K, Mileshkin, L, Lutgens, LCHW, Kitchener, HC, Brooks, S, Nijman, HW, Astreinidou, E, Putter, H, Creutzberg, CL, and de Boer, SM

Abstract

PURPOSE: Radiation therapy techniques have developed from 3-dimensional conformal radiation therapy (3DCRT) to intensity modulated radiation therapy (IMRT), with better sparing of the surrounding normal tissues. The current analysis aimed to investigate whether IMRT, compared to 3DCRT, resulted in fewer adverse events (AEs) and patient-reported symptoms in the randomized PORTEC-3 trial for high-risk endometrial cancer. METHODS AND MATERIALS: Data on AEs and patient-reported quality of life (QoL) of the PORTEC-3 trial were available for analysis. Physician-reported AEs were graded using Common Terminology Criteria for Adverse Events v3.0. QoL was assessed by the European Organisation for Research and Treatment of Cancer QLQC30, CX24, and OV28 questionnaires. Data were compared between 3DCRT and IMRT. A P value of ≤ .01 was considered statistically significant due to the risk of multiple testing. For QoL, combined scores 1 to 2 ("not at all" and "a little") versus 3 to 4 ("quite a bit" and "very much") were compared between the techniques. RESULTS: Of 658 evaluable patients, 559 received 3DCRT and 99 IMRT. Median follow-up was 74.6 months. During treatment no significant differences were observed, with a trend for more grade ≥3 AEs, mostly hematologic and gastrointestinal, after 3DCRT (37.7% vs 26.3%, P = .03). During follow-up, 15.4% (vs 4%) had grade ≥2 diarrhea, and 26.1% (vs 13.1%) had grade ≥2 hematologic AEs after 3DCRT (vs IMRT) (both P < .01). Among 574 (87%) patients evaluable for QoL, 494 received 3DCRT and 80 IMRT. During treatment, 37.5% (vs 28.6%) reported diarrhea after 3DCRT (vs IMRT) (P = .125); 22.1% (versus 10.0%) bowel urgency (P = 0039), and 18.2% and 8.6% abdominal cramps (P = .058). Other QoL scores showed no differences. CONCLUSIONS: IMRT resulted in fewer grade ≥3 AEs during treatment and significantly lower rates of grade ≥2 diarrhea and hematologic AEs during follow-up. Trends toward fewer patient-reported bowel urgency and abdominal cramps w

Published
2022

4. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial

Author

de Boer, S, Powell, M, Mileshkin, L, Katsaros, D, Bessette, P, Haie-Meder, C, Ottevanger, P, Ledermann, J, Khaw, P, D'Amico, R, Fyles, A, Baron, M, Jurgenliemk-Schulz, I, Kitchener, H, Nijman, H, Wilson, G, Brooks, S, Gribaudo, S, Provencher, D, Hanzen, C, Kruitwagen, R, Smit, V, Singh, N, Do, V, Lissoni, A, Nout, R, Feeney, A, Verhoeven-Adema, K, Putter, H, Creutzberg, C, Mccormack, M, Whitmarsh, K, Allerton, R, Gregory, D, Symonds, P, Hoskin, P, Adusumalli, M, Anand, A, Wade, R, Stewart, A, Taylor, W, Lutgens, L, Hollema, H, Pras, E, Snyers, A, Westerveld, G, Jobsen, J, Slot, A, Mens, J, Stam, T, Van Triest, B, Van der Steen-Banasik, E, De Winter, K, Quinn, M, Kolodziej, I, Pyman, J, Johnson, C, Capp, A, Fossati, R, Colombo, A, Carinelli, S, Ferrero, A, Artioli, G, Davidson, C, Mclachlin, C, Ghatage, P, Rittenberg, P, Souhami, L, Thomas, G, Duvillard, P, Berton-Rigaud, D, Tubiana-Mathieu, N, de Boer S. M., Powell M. E., Mileshkin L., Katsaros D., Bessette P., Haie-Meder C., Ottevanger P. B., Ledermann J. A., Khaw P., D'Amico R., Fyles A., Baron M. -H., Jurgenliemk-Schulz I. M., Kitchener H. C., Nijman H. W., Wilson G., Brooks S., Gribaudo S., Provencher D., Hanzen C., Kruitwagen R. F., Smit V. T. H. B. M., Singh N., Do V., Lissoni A., Nout R. A., Feeney A., Verhoeven-Adema K. W., Putter H., Creutzberg C. L., McCormack M., Whitmarsh K., Allerton R., Gregory D., Symonds P., Hoskin P. J., Adusumalli M., Anand A., Wade R., Stewart A., Taylor W., Lutgens L. C. H. W., Hollema H., Pras E., Snyers A., Westerveld G. H., Jobsen J. J., Slot A., Mens J. M., Stam T. C., Van Triest B., Van der Steen-Banasik E. M., De Winter K. A. J., Quinn M. A., Kolodziej I., Pyman J., Johnson C., Capp A., Fossati R., Colombo A., Carinelli S., Ferrero A., Artioli G., Davidson C., McLachlin C. M., Ghatage P., Rittenberg P. V. C., Souhami L., Thomas G., Duvillard P., Berton-Rigaud D., Tubiana-Mathieu N., de Boer, S, Powell, M, Mileshkin, L, Katsaros, D, Bessette, P, Haie-Meder, C, Ottevanger, P, Ledermann, J, Khaw, P, D'Amico, R, Fyles, A, Baron, M, Jurgenliemk-Schulz, I, Kitchener, H, Nijman, H, Wilson, G, Brooks, S, Gribaudo, S, Provencher, D, Hanzen, C, Kruitwagen, R, Smit, V, Singh, N, Do, V, Lissoni, A, Nout, R, Feeney, A, Verhoeven-Adema, K, Putter, H, Creutzberg, C, Mccormack, M, Whitmarsh, K, Allerton, R, Gregory, D, Symonds, P, Hoskin, P, Adusumalli, M, Anand, A, Wade, R, Stewart, A, Taylor, W, Lutgens, L, Hollema, H, Pras, E, Snyers, A, Westerveld, G, Jobsen, J, Slot, A, Mens, J, Stam, T, Van Triest, B, Van der Steen-Banasik, E, De Winter, K, Quinn, M, Kolodziej, I, Pyman, J, Johnson, C, Capp, A, Fossati, R, Colombo, A, Carinelli, S, Ferrero, A, Artioli, G, Davidson, C, Mclachlin, C, Ghatage, P, Rittenberg, P, Souhami, L, Thomas, G, Duvillard, P, Berton-Rigaud, D, Tubiana-Mathieu, N, de Boer S. M., Powell M. E., Mileshkin L., Katsaros D., Bessette P., Haie-Meder C., Ottevanger P. B., Ledermann J. A., Khaw P., D'Amico R., Fyles A., Baron M. -H., Jurgenliemk-Schulz I. M., Kitchener H. C., Nijman H. W., Wilson G., Brooks S., Gribaudo S., Provencher D., Hanzen C., Kruitwagen R. F., Smit V. T. H. B. M., Singh N., Do V., Lissoni A., Nout R. A., Feeney A., Verhoeven-Adema K. W., Putter H., Creutzberg C. L., McCormack M., Whitmarsh K., Allerton R., Gregory D., Symonds P., Hoskin P. J., Adusumalli M., Anand A., Wade R., Stewart A., Taylor W., Lutgens L. C. H. W., Hollema H., Pras E., Snyers A., Westerveld G. H., Jobsen J. J., Slot A., Mens J. M., Stam T. C., Van Triest B., Van der Steen-Banasik E. M., De Winter K. A. J., Quinn M. A., Kolodziej I., Pyman J., Johnson C., Capp A., Fossati R., Colombo A., Carinelli S., Ferrero A., Artioli G., Davidson C., McLachlin C. M., Ghatage P., Rittenberg P. V. C., Souhami L., Thomas G., Duvillard P., Berton-Rigaud D., and Tubiana-Mathieu N.

Abstract

Background: The PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy versus pelvic radiotherapy alone for women with high-risk endometrial cancer. We updated the analysis to investigate patterns of recurrence and did a post-hoc survival analysis. Methods: In the multicentre randomised phase 3 PORTEC-3 trial, women with high-risk endometrial cancer were eligible if they had International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage I, endometrioid grade 3 cancer with deep myometrial invasion or lymphovascular space invasion, or both; stage II or III disease; or stage I–III disease with serous or clear cell histology; were aged 18 years and older; and had a WHO performance status of 0–2. Participants were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or chemoradiotherapy (two cycles of cisplatin 50 mg/m2 given intravenously during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2 given intravenously), by use of a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage, and histological type. The co-primary endpoints were overall survival and failure-free survival. Secondary endpoints of vaginal, pelvic, and distant recurrence were analysed according to the first site of recurrence. Survival endpoints were analysed by intention-to-treat, and adjusted for stratification factors. Competing risk methods were used for failure-free survival and recurrence. We did a post-hoc analysis to analyse patterns of recurrence with 1 additional year of follow-up. The study was closed on Dec 20, 2013; follow-up is ongoing. This study is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138. Findings: Between Nov 23, 2006, and Dec 20, 2013, 686 women were enrolled, of whom 660 were eligible and evaluable (330 in the chemoradiotherapy group, and 330 in the rad

Published
2019

5. OC-0298 Toxicity and patient-reported symptoms after 3D-conformal or intensity-modulated pelvic radiotherapy

Author

Wortman, B., primary, Post, C., additional, Powell, M., additional, Khaw, P., additional, Fyles, A., additional, D’Amico, R., additional, Haie-Meder, C., additional, Jurgenliemk-Schulz, I., additional, McCormack, M., additional, Do, V., additional, Katsaros, D., additional, Bessette, P., additional, Baron, M., additional, Nout, R., additional, Whitmarsh, K., additional, Mileshkin, L., additional, Lutgens, L., additional, Kitchener, H., additional, Brooks, S., additional, Nijman, H., additional, Astreinidou, E., additional, Putter, H., additional, Creutzberg, C., additional, and de Boer, S., additional

Published
2021
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6. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial

Author

de Boer, S, Powell, M, Mileshkin, L, Katsaros, D, Bessette, P, Haie-Meder, C, Ottevanger, P, Ledermann, J, Khaw, P, Colombo, A, Fyles, A, Baron, M, Jurgenliemk-Schulz, I, Kitchener, H, Nijman, H, Wilson, G, Brooks, S, Carinelli, S, Provencher, D, Hanzen, C, Lutgens, L, Smit, V, Singh, N, Do, V, D'Amico, R, Nout, R, Feeney, A, Verhoeven-Adema, K, Putter, H, Creutzberg, C, Mccormack, M, Whitmarsh, K, Allerton, R, Gregory, D, Symonds, P, Hoskin, P, Adusumalli, M, Anand, A, Wade, R, Stewart, A, Taylor, W, Kruitwagen, R, Hollema, H, Pras, E, Snyers, A, Stalpers, L, Jobsen, J, Slot, A, Mens, J, Stam, T, Van Triest, B, Van der Steen - Banasik, E, De Winter, K, Quinn, M, Kolodziej, I, Pyman, J, Johnson, C, Capp, A, Fossati, R, Gribaudo, S, Lissoni, A, Ferrero, A, Artioli, G, Davidson, C, Mclachlin, C, Ghatage, P, Rittenberg, P, Souhami, L, Thomas, G, Duvillard, P, Berton-Rigaud, D, Tubiana-Mathieu, N, de Boer S. M., Powell M. E., Mileshkin L., Katsaros D., Bessette P., Haie-Meder C., Ottevanger P. B., Ledermann J. A., Khaw P., Colombo A., Fyles A., Baron M. -H., Jurgenliemk-Schulz I. M., Kitchener H. C., Nijman H. W., Wilson G., Brooks S., Carinelli S., Provencher D., Hanzen C., Lutgens L. C. H. W., Smit V. T. H. B. M., Singh N., Do V., D'Amico R., Nout R. A., Feeney A., Verhoeven-Adema K. W., Putter H., Creutzberg C. L., McCormack M., Whitmarsh K., Allerton R., Gregory D., Symonds P., Hoskin P. J., Adusumalli M., Anand A., Wade R., Stewart A., Taylor W., Kruitwagen R. F. P. M., Hollema H., Pras E., Snyers A., Stalpers L., Jobsen J. J., Slot A., Mens J. -W. M., Stam T. C., Van Triest B., Van der Steen - Banasik E. M., De Winter K. A. J., Quinn M. A., Kolodziej I., Pyman J., Johnson C., Capp A., Fossati R., Gribaudo S., Lissoni A. A., Ferrero A., Artioli G., Davidson C., McLachlin C. M., Ghatage P., Rittenberg P. V. C., Souhami L., Thomas G., Duvillard P., Berton-Rigaud D., Tubiana-Mathieu N., de Boer, S, Powell, M, Mileshkin, L, Katsaros, D, Bessette, P, Haie-Meder, C, Ottevanger, P, Ledermann, J, Khaw, P, Colombo, A, Fyles, A, Baron, M, Jurgenliemk-Schulz, I, Kitchener, H, Nijman, H, Wilson, G, Brooks, S, Carinelli, S, Provencher, D, Hanzen, C, Lutgens, L, Smit, V, Singh, N, Do, V, D'Amico, R, Nout, R, Feeney, A, Verhoeven-Adema, K, Putter, H, Creutzberg, C, Mccormack, M, Whitmarsh, K, Allerton, R, Gregory, D, Symonds, P, Hoskin, P, Adusumalli, M, Anand, A, Wade, R, Stewart, A, Taylor, W, Kruitwagen, R, Hollema, H, Pras, E, Snyers, A, Stalpers, L, Jobsen, J, Slot, A, Mens, J, Stam, T, Van Triest, B, Van der Steen - Banasik, E, De Winter, K, Quinn, M, Kolodziej, I, Pyman, J, Johnson, C, Capp, A, Fossati, R, Gribaudo, S, Lissoni, A, Ferrero, A, Artioli, G, Davidson, C, Mclachlin, C, Ghatage, P, Rittenberg, P, Souhami, L, Thomas, G, Duvillard, P, Berton-Rigaud, D, Tubiana-Mathieu, N, de Boer S. M., Powell M. E., Mileshkin L., Katsaros D., Bessette P., Haie-Meder C., Ottevanger P. B., Ledermann J. A., Khaw P., Colombo A., Fyles A., Baron M. -H., Jurgenliemk-Schulz I. M., Kitchener H. C., Nijman H. W., Wilson G., Brooks S., Carinelli S., Provencher D., Hanzen C., Lutgens L. C. H. W., Smit V. T. H. B. M., Singh N., Do V., D'Amico R., Nout R. A., Feeney A., Verhoeven-Adema K. W., Putter H., Creutzberg C. L., McCormack M., Whitmarsh K., Allerton R., Gregory D., Symonds P., Hoskin P. J., Adusumalli M., Anand A., Wade R., Stewart A., Taylor W., Kruitwagen R. F. P. M., Hollema H., Pras E., Snyers A., Stalpers L., Jobsen J. J., Slot A., Mens J. -W. M., Stam T. C., Van Triest B., Van der Steen - Banasik E. M., De Winter K. A. J., Quinn M. A., Kolodziej I., Pyman J., Johnson C., Capp A., Fossati R., Gribaudo S., Lissoni A. A., Ferrero A., Artioli G., Davidson C., McLachlin C. M., Ghatage P., Rittenberg P. V. C., Souhami L., Thomas G., Duvillard P., Berton-Rigaud D., and Tubiana-Mathieu N.

Abstract

Background: Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer. Methods: PORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup. Eligible women had high-risk endometrial cancer with FIGO 2009 stage I, endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular space invasion (or both), endometrioid-type stage II or III, or stage I to III with serous or clear cell histology. Women were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or radiotherapy and chemotherapy (consisting of two cycles of cisplatin 50 mg/m2 given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2) using a biased-coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The co-primary endpoints were overall survival and failure-free survival. We used the Kaplan-Meier method, log-rank test, and Cox regression analysis for final analysis by intention to treat and adjusted for stratification factors. The study was closed on Dec 20, 2013, after achieving complete accrual; follow-up is ongoing. PORTEC-3 is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138. Results: 686 women were enrolled between Nov 23, 2006, and Dec 20, 2013. 660 eligible patients were included in the final analysis, of whom 330 were assigned to chemoradiotherapy and 330 were assigned to radiotherapy. Median follow-up was 60·2 months (IQR 48·1–73·1). 5-year overall survival was 81·8% (95% CI

Published
2018

7. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial

Author

de Boer S. M., Powell M. E., Mileshkin L., Katsaros D., Bessette P., Haie-Meder C., Ottevanger P. B., Ledermann J. A., Khaw P., Colombo A., Fyles A., Baron M. -H., Jurgenliemk-Schulz I. M., Kitchener H. C., Nijman H. W., Wilson G., Brooks S., Carinelli S., Provencher D., Hanzen C., Lutgens L. C. H. W., Smit V. T. H. B. M., Singh N., Do V., D'Amico R., Nout R. A., Feeney A., Verhoeven-Adema K. W., Putter H., Creutzberg C. L., McCormack M., Whitmarsh K., Allerton R., Gregory D., Symonds P., Hoskin P. J., Adusumalli M., Anand A., Wade R., Stewart A., Taylor W., Kruitwagen R. F. P. M., Hollema H., Pras E., Snyers A., Stalpers L., Jobsen J. J., Slot A., Mens J. -W. M., Stam T. C., Van Triest B., Van der Steen - Banasik E. M., De Winter K. A. J., Quinn M. A., Kolodziej I., Pyman J., Johnson C., Capp A., Fossati R., Gribaudo S., Lissoni A. A., Ferrero A., Artioli G., Davidson C., McLachlin C. M., Ghatage P., Rittenberg P. V. C., Souhami L., Thomas G., Duvillard P., Berton-Rigaud D., Tubiana-Mathieu N., de Boer, S, Powell, M, Mileshkin, L, Katsaros, D, Bessette, P, Haie-Meder, C, Ottevanger, P, Ledermann, J, Khaw, P, Colombo, A, Fyles, A, Baron, M, Jurgenliemk-Schulz, I, Kitchener, H, Nijman, H, Wilson, G, Brooks, S, Carinelli, S, Provencher, D, Hanzen, C, Lutgens, L, Smit, V, Singh, N, Do, V, D'Amico, R, Nout, R, Feeney, A, Verhoeven-Adema, K, Putter, H, Creutzberg, C, Mccormack, M, Whitmarsh, K, Allerton, R, Gregory, D, Symonds, P, Hoskin, P, Adusumalli, M, Anand, A, Wade, R, Stewart, A, Taylor, W, Kruitwagen, R, Hollema, H, Pras, E, Snyers, A, Stalpers, L, Jobsen, J, Slot, A, Mens, J, Stam, T, Van Triest, B, Van der Steen - Banasik, E, De Winter, K, Quinn, M, Kolodziej, I, Pyman, J, Johnson, C, Capp, A, Fossati, R, Gribaudo, S, Lissoni, A, Ferrero, A, Artioli, G, Davidson, C, Mclachlin, C, Ghatage, P, Rittenberg, P, Souhami, L, Thomas, G, Duvillard, P, Berton-Rigaud, D, and Tubiana-Mathieu, N

Subjects
Canada, Antineoplastic Combined Chemotherapy Protocol, Paclitaxel, Time Factor, Risk Factor, Australia, Chemoradiotherapy, Adjuvant, Middle Aged, Carboplatin, Europe, Treatment Outcome, Gynecologic Surgical Procedures, Lymph Node Excision, Endometrial Neoplasm, Female, Radiotherapy, Adjuvant, Dose Fractionation, Radiation, Cisplatin, Neoplasm Grading, Carcinoma, Endometrioid, Aged, Human, Neoplasm Staging, New Zealand
Abstract

Background: Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer. Methods: PORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup. Eligible women had high-risk endometrial cancer with FIGO 2009 stage I, endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular space invasion (or both), endometrioid-type stage II or III, or stage I to III with serous or clear cell histology. Women were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or radiotherapy and chemotherapy (consisting of two cycles of cisplatin 50 mg/m2 given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2) using a biased-coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The co-primary endpoints were overall survival and failure-free survival. We used the Kaplan-Meier method, log-rank test, and Cox regression analysis for final analysis by intention to treat and adjusted for stratification factors. The study was closed on Dec 20, 2013, after achieving complete accrual; follow-up is ongoing. PORTEC-3 is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138. Results: 686 women were enrolled between Nov 23, 2006, and Dec 20, 2013. 660 eligible patients were included in the final analysis, of whom 330 were assigned to chemoradiotherapy and 330 were assigned to radiotherapy. Median follow-up was 60·2 months (IQR 48·1–73·1). 5-year overall survival was 81·8% (95% CI 77·5–86·2) with chemoradiotherapy versus 76·7% (72·1–81·6) with radiotherapy (adjusted hazard ratio [HR] 0·76, 95% CI 0·54–1·06; p=0·11); 5-year failure-free survival was 75·5% (95% CI 70·3–79·9) versus 68·6% (63·1–73·4; HR 0·71, 95% CI 0·53–0·95; p=0·022). Grade 3 or worse adverse events during treatment occurred in 198 (60%) of 330 who received chemoradiotherapy versus 41 (12%) of 330 patients who received radiotherapy (p

Published
2018

8. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial

Author

de Boer, Stephanie M, primary, Powell, Melanie E, additional, Mileshkin, Linda, additional, Katsaros, Dionyssios, additional, Bessette, Paul, additional, Haie-Meder, Christine, additional, Ottevanger, Petronella B, additional, Ledermann, Jonathan A, additional, Khaw, Pearly, additional, D'Amico, Romerai, additional, Fyles, Anthony, additional, Baron, Marie-Helene, additional, Jürgenliemk-Schulz, Ina M, additional, Kitchener, Henry C, additional, Nijman, Hans W, additional, Wilson, Godfrey, additional, Brooks, Susan, additional, Gribaudo, Sergio, additional, Provencher, Diane, additional, Hanzen, Chantal, additional, Kruitwagen, Roy F, additional, Smit, Vincent T H B M, additional, Singh, Naveena, additional, Do, Viet, additional, Lissoni, Andrea, additional, Nout, Remi A, additional, Feeney, Amanda, additional, Verhoeven-Adema, Karen W, additional, Putter, Hein, additional, Creutzberg, Carien L, additional, McCormack, M, additional, Whitmarsh, K, additional, Allerton, R, additional, Gregory, D, additional, Symonds, P, additional, Hoskin, PJ, additional, Adusumalli, M, additional, Anand, A, additional, Wade, R, additional, Stewart, A, additional, Taylor, W, additional, Lutgens, LCHW, additional, Hollema, H, additional, Pras, E, additional, Snyers, A, additional, Westerveld, GH, additional, Jobsen, JJ, additional, Slot, A, additional, Mens, JM, additional, Stam, TC, additional, Van Triest, B, additional, Van der Steen-Banasik, EM, additional, De Winter, KAJ, additional, Quinn, MA, additional, Kolodziej, I, additional, Pyman, J, additional, Johnson, C, additional, Capp, A, additional, Fossati, R, additional, Colombo, A, additional, Carinelli, S, additional, Ferrero, A, additional, Artioli, G, additional, Davidson, C, additional, McLachlin, CM, additional, Ghatage, P, additional, Rittenberg, PVC, additional, Souhami, L, additional, Thomas, G, additional, Duvillard, P, additional, Berton-Rigaud, D, additional, and Tubiana-Mathieu, N, additional

Published
2019
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10. Treatment: the role of contact X‐ray brachytherapy (Papillon) in the management of early rectal cancer.

Author

Sripadam, R., Whitmarsh, K., Sun Myint, A., Franklin, A., Stewart, A., Mills, J., Roy, R., and Dhadda, A.

Subjects
*RECTAL cancer, *RADIOISOTOPE brachytherapy, *X-rays
Abstract

The article focuses on the use of contact X-ray brachytherapy (CXB) to assess rectal caner during it's early stages inorder to manage and treat the cancer. It talks about the risk of mortality and morbidity associated with radical surgery for the treatment of rectal cancer in the patient. It tells about CXB being used for the treatment of rectal cancer and for improving the external beam radiotherapy.

Published
2019
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17. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial

Author

Carien L. Creutzberg, Petronella B. Ottevanger, Annamaria Ferrero, Luis Souhami, Pearly Khaw, GH Westerveld, Diane Provencher, Gillian Thomas, Jan Pyman, V. Do, Annerie Slot, C Davidson, G. Wilson, Stephanie M. de Boer, Peter Hoskin, C M McLachlin, Michael A. Quinn, Deborah Gregory, Remi A. Nout, Hans W. Nijman, J.J. Jobsen, Tanja C. Stam, Vincent T.H.B.M. Smit, K Whitmarsh, Paul Bessette, Roy F.P.M. Kruitwagen, W Taylor, Dionyssios Katsaros, Chantal Hanzen, Henry C Kitchener, M McCormack, Prafull Ghatage, Dominique Berton-Rigaud, J.W.M. Mens, Melanie E Powell, Elisabeth Pras, Jonathan A. Ledermann, Karen W Verhoeven-Adema, Harmen Hollema, Andrea Lissoni, Linda Mileshkin, Anjana Anand, Amanda Feeney, Sergio Gribaudo, Marie-Helene Baron, R Allerton, Hein Putter, Colin D. Johnson, P. Symonds, Ina M. Jürgenliemk-Schulz, Romerai D'Amico, Ilka Kolodziej, M Adusumalli, Naveena Singh, G Artioli, An Snyers, R Wade, Christine Haie-Meder, Roldano Fossati, Nicole Tubiana-Mathieu, Anthony Fyles, Silvestro Carinelli, Anne Capp, Alexandra J. Stewart, Kaj De Winter, B. van Triest, L.C.H.W. Lutgens, Susan Brooks, E. Van der Steen-Banasik, Pierre Duvillard, Pvc Rittenberg, Alessandro Colombo, de Boer, S, Powell, M, Mileshkin, L, Katsaros, D, Bessette, P, Haie-Meder, C, Ottevanger, P, Ledermann, J, Khaw, P, D'Amico, R, Fyles, A, Baron, M, Jurgenliemk-Schulz, I, Kitchener, H, Nijman, H, Wilson, G, Brooks, S, Gribaudo, S, Provencher, D, Hanzen, C, Kruitwagen, R, Smit, V, Singh, N, Do, V, Lissoni, A, Nout, R, Feeney, A, Verhoeven-Adema, K, Putter, H, Creutzberg, C, Mccormack, M, Whitmarsh, K, Allerton, R, Gregory, D, Symonds, P, Hoskin, P, Adusumalli, M, Anand, A, Wade, R, Stewart, A, Taylor, W, Lutgens, L, Hollema, H, Pras, E, Snyers, A, Westerveld, G, Jobsen, J, Slot, A, Mens, J, Stam, T, Van Triest, B, Van der Steen-Banasik, E, De Winter, K, Quinn, M, Kolodziej, I, Pyman, J, Johnson, C, Capp, A, Fossati, R, Colombo, A, Carinelli, S, Ferrero, A, Artioli, G, Davidson, C, Mclachlin, C, Ghatage, P, Rittenberg, P, Souhami, L, Thomas, G, Duvillard, P, Berton-Rigaud, D, Tubiana-Mathieu, N, MUMC+: MA Toegelatenen Obstetrie Gynaecologie (9), MUMC+: MA Obstetrie Gynaecologie (3), MUMC+: MA Arts Assistenten Obstetrie Gynaecologie (9), RS: GROW - R2 - Basic and Translational Cancer Biology, Obstetrie & Gynaecologie, Translational Immunology Groningen (TRIGR), and Targeted Gynaecologic Oncology (TARGON)

Subjects
0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, MED/40 - GINECOLOGIA E OSTETRICIA, MULTICENTER, THERAPY, CARCINOMA PATIENTS, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Survival analysis, MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA, III TRIAL, Manchester Cancer Research Centre, Performance status, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Endometrial cancer, Hazard ratio, CHEMOTHERAPY, OPEN-LABEL, medicine.disease, Carboplatin, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], IRRADIATION, 3. Good health, Radiation therapy, 030104 developmental biology, Oncology, chemistry, Endometrial cancer, radiotherapy, chemotherapy, adjuvant treatment, 030220 oncology & carcinogenesis, MED/06 - ONCOLOGIA MEDICA, RADIATION, Lymphadenectomy, business, Chemoradiotherapy
Abstract

BACKGROUND:The PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy versus pelvic radiotherapy alone for women with high-risk endometrial cancer. We updated the analysis to investigate patterns of recurrence and did a post-hoc survival analysis.METHODS:In the multicentre randomised phase 3 PORTEC-3 trial, women with high-risk endometrial cancer were eligible if they had International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage I, endometrioid grade 3 cancer with deep myometrial invasion or lymphovascular space invasion, or both; stage II or III disease; or stage I-III disease with serous or clear cell histology; were aged 18 years and older; and had a WHO performance status of 0-2. Participants were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or chemoradiotherapy (two cycles of cisplatin 50 mg/m2 given intravenously during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2 given intravenously), by use of a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage, and histological type. The co-primary endpoints were overall survival and failure-free survival. Secondary endpoints of vaginal, pelvic, and distant recurrence were analysed according to the first site of recurrence. Survival endpoints were analysed by intention-to-treat, and adjusted for stratification factors. Competing risk methods were used for failure-free survival and recurrence. We did a post-hoc analysis to analyse patterns of recurrence with 1 additional year of follow-up. The study was closed on Dec 20, 2013; follow-up is ongoing. This study is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138.FINDINGS:Between Nov 23, 2006, and Dec 20, 2013, 686 women were enrolled, of whom 660 were eligible and evaluable (330 in the chemoradiotherapy group, and 330 in the radiotherapy-alone group). At a median follow-up of 72·6 months (IQR 59·9-85·6), 5-year overall survival was 81·4% (95% CI 77·2-85·8) with chemoradiotherapy versus 76·1% (71·6-80·9) with radiotherapy alone (adjusted hazard ratio [HR] 0·70 [95% CI 0·51-0·97], p=0·034), and 5-year failure-free survival was 76·5% (95% CI 71·5-80·7) versus 69·1% (63·8-73·8; HR 0·70 [0·52-0·94], p=0·016). Distant metastases were the first site of recurrence in most patients with a relapse, occurring in 78 of 330 women (5-year probability 21·4%; 95% CI 17·3-26·3) in the chemoradiotherapy group versus 98 of 330 (5-year probability 29·1%; 24·4-34·3) in the radiotherapy-alone group (HR 0·74 [95% CI 0·55-0·99]; p=0·047). Isolated vaginal recurrence was the first site of recurrence in one patient (0·3%; 95% CI 0·0-2·1) in both groups (HR 0·99 [95% CI 0·06-15·90]; p=0·99), and isolated pelvic recurrence was the first site of recurrence in three women (0·9% [95% CI 0·3-2·8]) in the chemoradiotherapy group versus four (0·9% [95% CI 0·3-2·8]) in the radiotherapy-alone group (HR 0·75 [95% CI 0·17-3·33]; p=0·71). At 5 years, only one grade 4 adverse event (ileus or obstruction) was reported (in the chemoradiotherapy group). At 5 years, reported grade 3 adverse events did not differ significantly between the two groups, occurring in 16 (8%) of 201 women in the chemoradiotherapy group versus ten (5%) of 187 in the radiotherapy-alone group (p=0·24). The most common grade 3 adverse event was hypertension (in four [2%] women in both groups). At 5 years, grade 2 or worse adverse events were reported in 76 (38%) of 201 women in the chemoradiotherapy group versus 43 (23%) of 187 in the radiotherapy-alone group (p=0·002). Sensory neuropathy persisted more often after chemoradiotherapy than after radiotherapy alone, with 5-year rates of grade 2 or worse neuropathy of 6% (13 of 201 women) versus 0% (0 of 187). No treatment-related deaths were reported.INTERPRETATION:This updated analysis shows significantly improved overall survival and failure-free survival with chemoradiotherapy versus radiotherapy alone. This treatment schedule should be discussed and recommended, especially for women with stage III or serous cancers, or both, as part of shared decision making between doctors and patients. Follow-up is ongoing to evaluate long-term survival.FUNDING:Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council, Project Grant, Cancer Australia Grant, Italian Medicines Agency, and the Canadian Cancer Society Research Institute.

Published
2019

18. Radiation Therapy Techniques and Treatment-Related Toxicity in the PORTEC-3 Trial: Comparison of 3-Dimensional Conformal Radiation Therapy Versus Intensity-Modulated Radiation Therapy.

Author

Wortman BG, Post CCB, Powell ME, Khaw P, Fyles A, D'Amico R, Haie-Meder C, Jürgenliemk-Schulz IM, McCormack M, Do V, Katsaros D, Bessette P, Baron MH, Nout RA, Whitmarsh K, Mileshkin L, Lutgens LCHW, Kitchener HC, Brooks S, Nijman HW, Astreinidou E, Putter H, Creutzberg CL, and de Boer SM

Subjects
Humans, Quality of Life, Radiotherapy Planning, Computer-Assisted methods, Radiotherapy, Conformal adverse effects, Radiotherapy, Conformal methods, Radiotherapy, Intensity-Modulated adverse effects, Radiotherapy, Intensity-Modulated methods
Abstract

Purpose: Radiation therapy techniques have developed from 3-dimensional conformal radiation therapy (3DCRT) to intensity modulated radiation therapy (IMRT), with better sparing of the surrounding normal tissues. The current analysis aimed to investigate whether IMRT, compared to 3DCRT, resulted in fewer adverse events (AEs) and patient-reported symptoms in the randomized PORTEC-3 trial for high-risk endometrial cancer., Methods and Materials: Data on AEs and patient-reported quality of life (QoL) of the PORTEC-3 trial were available for analysis. Physician-reported AEs were graded using Common Terminology Criteria for Adverse Events v3.0. QoL was assessed by the European Organisation for Research and Treatment of Cancer QLQC30, CX24, and OV28 questionnaires. Data were compared between 3DCRT and IMRT. A P value of ≤ .01 was considered statistically significant due to the risk of multiple testing. For QoL, combined scores 1 to 2 ("not at all" and "a little") versus 3 to 4 ("quite a bit" and "very much") were compared between the techniques., Results: Of 658 evaluable patients, 559 received 3DCRT and 99 IMRT. Median follow-up was 74.6 months. During treatment no significant differences were observed, with a trend for more grade ≥3 AEs, mostly hematologic and gastrointestinal, after 3DCRT (37.7% vs 26.3%, P = .03). During follow-up, 15.4% (vs 4%) had grade ≥2 diarrhea, and 26.1% (vs 13.1%) had grade ≥2 hematologic AEs after 3DCRT (vs IMRT) (both P < .01). Among 574 (87%) patients evaluable for QoL, 494 received 3DCRT and 80 IMRT. During treatment, 37.5% (vs 28.6%) reported diarrhea after 3DCRT (vs IMRT) (P = .125); 22.1% (versus 10.0%) bowel urgency (P = 0039), and 18.2% and 8.6% abdominal cramps (P = .058). Other QoL scores showed no differences., Conclusions: IMRT resulted in fewer grade ≥3 AEs during treatment and significantly lower rates of grade ≥2 diarrhea and hematologic AEs during follow-up. Trends toward fewer patient-reported bowel urgency and abdominal cramps were observed after IMRT compared to 3DCRT., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2022
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20. Dose Escalation Using Contact X-ray Brachytherapy After External Beam Radiotherapy as Nonsurgical Treatment Option for Rectal Cancer: Outcomes From a Single-Center Experience.

Author

Sun Myint A, Smith FM, Gollins S, Wong H, Rao C, Whitmarsh K, Sripadam R, Rooney P, Hershman M, and Pritchard DM

Subjects
Adenocarcinoma pathology, Adenocarcinoma secondary, Adenocarcinoma surgery, Adult, Aged, Aged, 80 and over, Brachytherapy adverse effects, Chemoradiotherapy, Disease-Free Survival, Female, Humans, Male, Middle Aged, Neoplasm Recurrence, Local surgery, Neoplasm, Residual, Rectal Neoplasms pathology, Rectal Neoplasms surgery, Salvage Therapy methods, Treatment Outcome, Adenocarcinoma radiotherapy, Brachytherapy methods, Radiotherapy Dosage, Rectal Neoplasms radiotherapy
Abstract

Purpose: To review the outcomes of rectal cancer patients treated with a nonsurgical approach using contact x-ray brachytherapy (CXB) when suspicious residual disease (≤3 cm) was present after external beam chemoradiation therapy/radiation therapy (EBCRT/EBRT)., Methods and Materials: Outcome data for rectal cancer patients referred to our institution from 2003 to 2012 were retrieved from an institutional database. These patients were referred after initial local multidisciplinary team discussion because they were not suitable for, or had refused, surgery. All selected patients received a CXB boost after EBCRT/EBRT. Most patients received a total of 90 Gy of CXB delivered in 3 fractions over 4 weeks., Results: The median follow-up period was 2.5 years (range 1.2-8.3). Of 345 consecutive patients with rectal cancer referred to us, 83 with suspicious residual disease (≤3 cm) after EBCRT/EBRT were identified for a CXB boost. Their median age was 72 years (range 36-87), and 58 (69.9%) were men. The initial tumor stages were cT2 (n = 28) and cT3 (n = 55), and 54.2% were node positive. A clinical complete response (cCR) was achieved in 53 patients (63.8%) after the CXB boost that followed EBCRT/EBRT. Of these 53 patients, 7 (13.2%) developed a relapse after achieving a cCR, and the 6 patients (11.6%) with nonmetastatic regrowth underwent salvage surgery (100%). At the end of the study period, 69 of 83 patients (83.1%) were cancer free., Conclusions: Our data suggest that a CXB boost for selected patients with suspicious residual disease (≤3 cm) after EBCRT/EBRT can be offered as an alternative to radical surgery. In our series, patients with a sustained cCR had a low rate of local regrowth, and those with nonmetastatic regrowth could be salvaged successfully. This approach could provide an alternative treatment option for elderly or comorbid patients who are not suitable for surgery and those with rectal cancer who wish to avoid surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Published
2018
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21. Dose escalation using contact X-ray brachytherapy (Papillon) for rectal cancer: does it improve the chance of organ preservation?

Author

Sun Myint A, Smith FM, Gollins SW, Wong H, Rao C, Whitmarsh K, Sripadam R, Rooney P, Hershman MJ, Fekete Z, Perkins K, and Pritchard DM

Subjects
Adult, Aged, Aged, 80 and over, Critical Pathways, Disease-Free Survival, Dose-Response Relationship, Radiation, Endosonography, Female, Humans, Kaplan-Meier Estimate, Magnetic Resonance Imaging, Male, Middle Aged, Neoplasm Recurrence, Local prevention & control, Organ Sparing Treatments methods, Retrospective Studies, Tomography, X-Ray Computed, Treatment Outcome, Brachytherapy methods, Neoplasm Recurrence, Local radiotherapy, Rectal Neoplasms radiotherapy
Abstract

Objective: A watch and wait policy for patients with a clinical complete response (cCR) after external beam chemoradiotherapy (EBCRT) for rectal cancer is an attractive option. However, approximately one-third of tumours will regrow, which requires surgical salvage for cure. We assessed whether contact X-ray brachytherapy (CXB) can improve organ preservation by avoiding surgery for local regrowth., Methods: From our institutional database, we identified 200 of 573 patients treated by CXB from 2003 to 2012. Median age was 74 years (range 32-94), and 134 (67%) patients were males. Histology was confirmed in all patients and was staged using CT scan, MRI or endorectal ultrasound. All patients received combined CXB and EBCRT, except 17 (8.5%) who had CXB alone., Results: Initial cCR was achieved in 144/200 (72%) patients. 38/56 (68%) patients who had residual tumour received immediate salvage surgery. 16/144 (11%) patients developed local relapse after cCR, and 124/144 (86%) maintained cCR. At median follow up of 2.7 years, 161 (80.5%) patients were free of cancer. The main late toxicity was bleeding (28%). Organ preservation was achieved in 124/200 (62%) patients., Conclusion: Our data suggest that CXB can reduce local regrowth to 11% compared with around 30% after EBCRT alone. Organ preservation of 62% achieved was higher than reported in most published watch and wait studies. Advances in knowledge: CXB is a promising treatment option to avoid salvage surgery for local regrowth, which can improve the chance of organ preservation in patients who are not suitable for or refuse surgery.

Published
2017
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22. Factors affecting the outcome of autologous bone marrow transplantation.

Author

Gulati SC, Yahalom J, Whitmarsh K, Clarkson BD, and Gee T

Subjects
Antineoplastic Combined Chemotherapy Protocols therapeutic use, Combined Modality Therapy, Cyclophosphamide administration & dosage, Etoposide administration & dosage, Hodgkin Disease surgery, Hodgkin Disease therapy, Humans, Leukemia, Myeloid, Acute surgery, Leukemia, Myeloid, Acute therapy, Lymphoma, Non-Hodgkin mortality, Lymphoma, Non-Hodgkin surgery, Lymphoma, Non-Hodgkin therapy, Prognosis, Remission Induction, Survival Rate, Transplantation, Autologous, Whole-Body Irradiation, Bone Marrow Transplantation mortality
Abstract

Various protocols have been used at Memorial Sloan-Kettering Cancer Center to improve the results of autologous bone marrow transplantation (ABMT) for hematopoietic malignancies. Results suggest that patients who undergo ABMT while in complete remission (after induction or reinduction treatment) do better than those who undergo ABMT in incomplete remission. In patients with relapsed or refractory lymphoma, the addition of etoposide to the total body irradiation/cyclophosphamide conditioning regimen has decreased the relapse rate from 53% to 7%. For patients with refractory or relapsed Hodgkin's disease, the dosages of different drugs can be altered to improve the overall success. Dose escalation of etoposide shows significant promise. Relapse after ABMT and/or toxic complications are the main factors that need to be addressed in the future. Pulmonary toxicity occurs mainly in patients with mediastinal disease. Factors that can decrease relapse rate and toxicity are discussed.

Published
1991
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23. Results of autologous bone marrow transplantation for acute leukaemia.

Author

Gulati SC, Whitmarsh K, Reich L, Berman E, Yahalom J, Yopp J, Clarkson B, and Gee T

Subjects
Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Clinical Trials as Topic, Combined Modality Therapy, Female, Humans, Leukemia, Myeloid, Acute drug therapy, Male, Middle Aged, Transplantation, Autologous, Bone Marrow Transplantation, Leukemia, Myeloid, Acute surgery
Published
1989

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