For high risk prostate cancer, the treatment volumes and even dose levels are still a controversial issue. The aim of this study is to evaluate the dosemetric parameters and acute toxicity of dose-escalated whole pelvis (WP) Intensity Modulated Radiation Therapy (IMRT) and volumetric modulated arc therapy (VMAT) prostate boost following neoadjuvant and concomitant with androgen deprivation therapy in high-risk prostate cancer patients. This analysis included 73 high-risk prostate cancer patients treated with WP-IMRT followed by boost to the prostate by VMAT to total dose of 80 Gy; between January 2014 and October 2016. Androgen deprivation therapy (ADT) was given for all patients before and during radiation therapy. Drawing the dose volume histograms (DVHs) was done for planning target volumes (PTVs), including Prostate PTV & nodal PTV, and organs at risk including rectum, bladder, femoral heads, and bowel bag for the plans. Acute radiation toxicities were reported during the radiation course and the following 3 months. The DVH analysis showed good coverage of PTVs and organs at risk doses were acceptable. No recorded acute Grade ≥ 3 toxicity. Acute grade 1 toxicity for Gastrointestinal (GI) and Genitourinary (GU) were 65% and 35% respectively, while Grade 2 toxicity was 30% for both. The Proctitis and frequency were the commonest acute toxicity and were maximal during the 5th week of radiation therapy. Dose escalation in two phases utilizing Simultaneous integrated boost (SIB) combined with ADT in high risk prostate cancer patient is feasible and associated with acceptable acute GI and GU toxicity.
Beckendorf, V., Guerif, S., Le Prise, E., et al. (2011) 70 Gy versus 80 Gy in Localized Prostate Cancer: 5-Year Results of GETUG 06 Randomized Trial. International Journal of Radiation Oncology, Biology, Physics, 80, 1056-1063. https://doi.org/10.1016/j.ijrobp.2010.03.049
Zietman, A.L., DeSilvio, M.L., Slater, J.D., et al. (2005) Comparison of Conventional-Dose vs High-Dose Conformal Radiation Therapy in Clinically Localized Adenocarcinoma of the Prostate: A Randomized Controlled Trial. The Journal of the American Medical Association, 294, 1233-1239. https://doi.org/10.1001/jama.294.10.1233
Al-Mamgani, A., van Putten, W.L., van der Wielen, G.J., Levendag, P.C. and Incrocci, L. (2011) Dose Escalation and Quality of Life in Patients with Localized Prostate Cancer Treated with Radiotherapy: Long-Term Results of the Dutch Randomized Dose-Escalation Trial (CKTO 96–10 Trial). International Journal of Radiation Oncology, Biology, Physics, 79, 1004-1012. https://doi.org/10.1016/j.ijrobp.2009.12.039
Roach, M., De Silvio, M., Lawton, C., et al. (2003) Phase III Trial Comparing Whole-Pelvis versus Prostate-Only Radiotherapy and Neoadjuvant versus Adjuvant Combined Androgen Suppression: Radiation Therapy Oncology Group 9413. Journal of Clinical Oncology, 21, 1904-1911. https://doi.org/10.1200/JCO.2003.05.004
Lawton, C.A., De Silvio, M., Roach, M., et al. (2007) An Update of the Phase III Trial Comparing Whole Pelvic to Prostate Only Radiotherapy and Neoadjuvant to Adjuvant Total Androgen Suppression: Updated Analysis of RTOG 94-13, with Emphasis on Unexpected Hormone/Radiation Interactions. International Journal of Radiation Oncology, Biology, Physics, 69, 646-655. https://doi.org/10.1016/j.ijrobp.2007.04.003
Pahlajani, N., Ruth, K.J., Buyyounouski, M.K., et al. (2012) Radiotherapy Doses of 80 Gy and Higher Are Associated with Lower Mortality in Men with Gleason Score 8 to 10 Prostate Cancer. International Journal of Radiation Oncology, Biology, Physics, 82, 1949-1956. https://doi.org/10.1016/j.ijrobp.2011.04.005
Zelefsky, M.J., Pei, X., Chou, J.F., et al. (2011) Dose Escalation for Prostate Cancer Radiotherapy: Predictors of Long-Term Biochemical Tumor Control and Distant Metastases-Free Survival Outcomes. European Urology, 60, 1133-1139. https://doi.org/10.1016/j.eururo.2011.08.029
Hennequin, C., Richaud, P.M., Roca, L., et al. (2015) Randomized Phase 3 Trial of Dose Escalation (80 vs 70 Gy) in High-Risk Prostate Cancers Combined with Long-Term Androgen Deprivation: GETUG-AFU 18 Trial, Acute and 1-Year Toxicities. International Journal of Radiation Oncology, Biology, Physics, 93, S44-S45. https://doi.org/10.1016/j.ijrobp.2015.07.107
Sanguineti, G., Cavey, M.L., Endres, E.J., et al. (2006) Does Treatment of the Pelvic nodes with IMRT Increase Late Rectal Toxicity over Conformal Prostate-Only Radiotherapy to 76 Gy? Strahlentherapie und Onkologie, 182, 543-549. https://doi.org/10.1007/s00066-006-1586-9
Wang-Chesebro, A., Xia, P., Coleman, J., Akazawa, C. and Roach, M, (2006) Intensity Modulated Radiotherapy Improves Lymph Node Coverage and Dose to Critical Structures Compared with Three-Dimensional Conformal Radiation Therapy in Clinically Localized Prostate Cancer. International Journal of Radiation Oncology, Biology, Physics, 66, 654-662. https://doi.org/10.1016/j.ijrobp.2006.05.037
Sheets, N.C., Goldin, G.H., Meyer, A.M., et al. (2012) Intensity-Modulated Radiation Therapy, Proton Therapy, or Conformal Radiation Therapy and Morbidity and Disease Control in Localized Prostate Cancer. The Journal of the American Medical Association, 307, 1611-1620. https://doi.org/10.1001/jama.2012.460
Muren, L.P., Wasbo, E., Helle, S.I., et al. (2008) Intensity-Modulated Radiotherapy of Pelvic Lymph Nodes in Locally Advanced Prostate Cancer: Planning Procedures and Early Experiences. International Journal of Radiation Oncology, Biology, Physics, 71, 1034-1041. https://doi.org/10.1016/j.ijrobp.2007.11.060
Pervez, N., Small, C., MacKenzie, M., et al. (2010) Acute Toxicity in Highrisk Prostate Cancer Patients Treated with Androgen Suppression and Hypofractionated Intensity-Modulated Radiotherapy. International Journal of Radiation Oncology, Biology, Physics, 76, 57-64. https://doi.org/10.1016/j.ijrobp.2009.01.048
Bayley, A., Rosewall, T., Craig, T., et al. (2010) Clinical Application of High-Dose, Image-Guided Intensity-Modulated Radiotherapy in High-Risk Prostate Cancer. International Journal of Radiation Oncology, Biology, Physics, 77, 477-483. https://doi.org/10.1016/j.ijrobp.2009.05.006
Guckenberger, M., Baier, K., Richter, A., Vordermark, D. and Flentje, M. (2008) Does Intensity Modulated Radiation Therapy (IMRT) Prevent Additional Toxicity of Treating the Pelvic Lymph Nodes Compared to Treatment of the Prostate Only? Radiation Oncology, 3, 3. https://doi.org/10.1186/1748-717X-3-3
Zhang, P., Happersett, L., Hunt, M., et al. (2010) Volumetric Modulated Arc Therapy: Planning and Evaluation for Prostate Cancer Cases. International Journal of Radiation Oncology, Biology, Physics, 76, 1456-1462. https://doi.org/10.1016/j.ijrobp.2009.03.033
Aznar, M.C., Petersen, P.M., Logadottir, A., et al. (2010) Rotational Radiotherapy for Prostate Cancer in Clinical Practice. Radiotherapy and Oncology, 97, 480-484. https://doi.org/10.1016/j.radonc.2010.09.014
Kopp, R.W., Duff, M., Catalfamo, F., et al. (2011) VMAT vs. 7-Field-IMRT: Assessing the Dosimetric Parameters of Prostate Cancer Treatment with a 292-Patient Sample. Medical Dosimetry, 36, 365-372. https://doi.org/10.1016/j.meddos.2010.09.004
Edge, S.B. and Compton, C.C. (2010) The American Joint Committee on Cancer: The 7th Edition of the AJCC Cancer Staging Manual and the Future of TNM. Annals of Surgical Oncology, 17, 1471-1474. https://doi.org/10.1245/s10434-010-0985-4
Lawton, C.A.F., Michalski, J., El-Naqa, I., et al. (2009) RTOG GU Radiation Oncology Specialists Reach Consensus on Pelvic Lymph Node Volumes for High-Risk Prostate Cancer. International Journal of Radiation Oncology, Biology, Physics, 74, 383-387. https://doi.org/10.1016/j.ijrobp.2008.08.002
Gay, H.A., Barthold, H.J., O’Meara, E., et al. (2012) Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas. International Journal of Radiation Oncology, Biology, Physics, 83, e353-e362. https://doi.org/10.1016/j.ijrobp.2012.01.023
Morikawa, L.K. and Roach, M. (2011) Pelvic Nodal Radiotherapy in Patients with Unfavorable Intermediate and High-Risk Prostate Cancer: Evidence, Rationale, and Future Directions. International Journal of Radiation Oncology, Biology, Physics, 80, 6-16. https://doi.org/10.1016/j.ijrobp.2010.11.074
Pommier, P., Chabaud, S., Lagrange, J.L., et al. (2007) Is There a Role for Pelvic Irradiation in Localized Prostate Adenocarcinoma? Preliminary Results of GETUG-01. Journal of Clinical Oncology, 25, 5366-5373. https://doi.org/10.1200/JCO.2006.10.5171
Radiation Therapy Oncology Group (2011) Androgen Deprivation Therapy and High Dose Radiotherapy with or without Whole-Pelvic Radiotherapy in Unfavorable Intermediate or Favorable High Risk Prostate Cancer: A Phase III Randomized Trial.
Kaidar-Person, O., Roach, M. and Crehange, G. (2013) Whole-Pelvic Nodal Radiation Therapy in the Context of Hypofractionation for High-Risk Prostate Cancer Patients: A Step forward. International Journal of Radiation Oncology, Biology, Physics, 86, 600-605. https://doi.org/10.1016/j.ijrobp.2013.02.006
Yoo, S., Wu, Q.J., Lee, W.R. and Yin, F.-F. (2010) Radiotherapy Treatment Plans with Rapid Arc for Prostate Cancer Involving Seminal Vesicles and Lymph Nodes. International Journal of Radiation Oncology, Biology, Physics, 76, 935-942. https://doi.org/10.1016/j.ijrobp.2009.07.1677
Riou, O., Mothe, P.R., Azria, D., et al. (2013) Simultaneous Integrated Boost Plan Comparison of Volumetric-Modulated Arc Therapy and Sliding Window Intensity-Modulated Radiotherapy for Whole Pelvis Irradiation of Locally Advanced Prostate Cancer. Journal of Applied Clinical Medical Physics, 14, 26-35. https://doi.org/10.1120/jacmp.v14i4.4094
Deville, C., Both, S., Hwang, W.T., Tochner, Z. and Vapiwala, N. (2010) Clinical Toxicities and Dosimetric Parameters after Whole-Pelvis versus Prostate-Only Intensity-Modulated Radiation Therapy for Prostate Cancer. International Journal of Radiation Oncology, Biology, Physics, 78, 763-772. https://doi.org/10.1016/j.ijrobp.2009.08.043
Ishii, K., Ogino, R., Hosokawa, Y., et al. (2015) Whole-Pelvic Volumetric-Modulated Arc Therapy for High-Risk Prostate Cancer: Treatment Planning and Acute Toxicity. Journal of Radiation Research, 56, 141-150. https://doi.org/10.1093/jrr/rru086
Vargas, C., Martinez, A., Kestin, L.L., et al. (2005) Dose-Volume Analysis of Predictors for Chronic Rectal Toxicity after Treatment of Prostate Cancer with Adaptive Image-Guided Radiotherapy. International Journal of Radiation Oncology, Biology, Physics, 62, 1297-308. https://doi.org/10.1016/j.ijrobp.2004.12.052
Michalski, J.M., Yan, Y., Watkins-Bruner, D., et al. (2013) Preliminary Toxicity Analysis of 3-Dimensional Conformal Radiation Therapy versus Intensity Modulated Radiation Therapy on the High-Dose Arm of the Radiation Therapy Oncology Group 0126 Prostate Cancer Trial. International Journal of Radiation Oncology, Biology, Physics, 87, 932-938. https://doi.org/10.1016/j.ijrobp.2013.07.041
De Meerleer, G., Vakaet, L., Meersschout, S., et al. (2004) Intensitymodulated Radiotherapy as Primary Treatment for Prostate Cancer: Acute Toxicity in 114 Patients. International Journal of Radiation Oncology, Biology, Physics, 60, 777-787. https://doi.org/10.1016/j.ijrobp.2004.04.017
Arcangeli, S., Saracino, B., Grazia, M., et al. (2007) Analysis of Toxicity in Patients with High Risk Prostate Cancer Treated with Intensitymodulated Pelvic Radiation Therapy and Simultaneous Integrated Dose Escalation to Prostate Area. Radiotherapy and Oncology, 84, 148-155. https://doi.org/10.1016/j.radonc.2007.06.011
Ferjani, S., Huang, G., Shang, Q., et al. (2013) Alignment Focus of Daily Image Guidance for Concurrent Treatment of Prostate and Pelvic Lymph Nodes. International Journal of Radiation Oncology, Biology, Physics, 87, 383-389. https://doi.org/10.1016/j.ijrobp.2013.06.003
Chung, H.T., Xia, P., Chan, L.W., Park-Somers, E. and Roach, M. (2009) Does Image-Guided Radiotherapy Improve Toxicity Profile in Whole Pelvic-Treated High-Risk Prostate Cancer? Comparison between IG-IMRT and IMRT. International Journal of Radiation Oncology, Biology, Physics, 73, 53-60. https://doi.org/10.1016/j.ijrobp.2008.03.015
Soloway, M.S., Sharifi, R., Wajsman, Z., McLeod, D., Wood Jr., D.P. and Puras-Baez, A. (1995) Randomized Prospective Study Comparing Radical Prostatectomy alone versus Radical Prostatectomy Preceded by Androgen Blockade in Clinical Stage B2 (T2bNxM0) Prostate Cancer. The Lupron Depot Neoadjuvant Prostate Cancer Study Group. Journal of Urology, 154, 424-428. https://doi.org/10.1016/S0022-5347(01)67067-8
Mercader, M., Bodner, B.K., Moser, M.T., Kwon, P.S., Park, E.S., Manecke, R.G., et al. 2001. T-Cell Infiltration of the Prostate Induced by Androgen Withdrawal in Patients with Prostate Cancer. Proceedings of the National Academy of Sciences of the United States of America, 98, 14565-14570. https://doi.org/10.1073/pnas.251140998