1072 - Interim Analysis of a Phase 2 Single Arm Trial of Extended Lymph Node Proton Irradiation for High Risk Prostate Cancer
Presenter(s)
P. R. Patel1, V. R. Dhere1, N. Sebastian2, S. A. Patel3, M. Rupji4, K. D. Godette5, B. Hershatter1, and A. Jani3; 1Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, 2Emory Proton Therapy Center, Atlanta, OH, 3Department of Radiation Oncology, Emory University, Atlanta, GA, 4Department of Biostatistics & Bioinformatics, Rollins School of Public Health, and Winship Cancer Institute at Emory University, Atlanta, GA, 5Winship Cancer Institute, Department of Radiation Oncology, Emory University, Atlanta, GA
Purpose/Objective(s): In high risk prostate cancer (PCa), irradiation of the pelvic lymph nodes is associated with improved biochemical relapse free survival and distant metastasis free survival with modest worsening of acute grade 2 gastrointestinal (GI) toxicity (30-45% incidence). Patterns of failure analyses using PET imaging show up to 50% of lymph node recurrences are outside of the RTOG consensus pelvic lymph node atlas with 20-40% involvement of the lower paraaortic (PA) lymph nodes. We hypothesized that the use of proton therapy for extended lymph node irradiation of the pelvic and PA lymph nodes would be feasible and associated with acceptable GI toxicity.
Materials/Methods: Patients with high risk or node-positive PCa were enrolled on a prospective phase 2, single institution, single arm trial. Lymph node metastases up to the L1-L2 interspace were allowed. All patients were treated with androgen deprivation therapy and intensity modulated proton therapy. The elective lymph node volume included the pelvic and lower PA lymph nodes up to the L1-L2 interspace. Positive lymph nodes were targeted for simultaneous integrated boost (SIB). The prostate and seminal vesicles were boosted with sequential boost (SeqB), SIB, or brachytherapy (BT). The trial (planned n=30) was powered to detect at least a 50% reduction in Common Toxicities Criteria for Adverse Events (CTCAE) version 5 acute grade 2+ GI toxicity, the primary endpoint, compared to the historical standard at the time of trial conception (47% in RTOG 9413). The rate of acute grade 2+ GI and GU toxicity was compared to the whole pelvis arm of the POP-RT trial using Fisher’s exact test.
Results: Of the 27 consented patients, 6 were ineligible and 1 withdrew and thus this initial report includes 20 patients enrolled from 4/2021 to 9/2024. The median age was 69 years (range 51-87) and 13/20 (65%) patients were node positive. The median PSA was 28.1 ng/mL (interquartile range [IQTR] 16.0-53.5). Prostate/SV boost was delivered via SeqB, SIB or BT in 12, 5, and 3 patients, respectively. PET positive lymph nodes received an SIB node boost dose of 55-62.5 Gy in 25-28 fractions. The mean bowel V45Gy was 36.4 ml (IQRT 10.5-39.4). The median follow-up is 16.5 months (range 1-44). One patient developed grade 2 acute GI toxicity (crude rate 5% vs. 32.7% in POP-RT, p=0.01). The rate of grade 2+ acute GU toxicity was 50% with 1 grade 3 event for retention after BT (vs. 32.7% in POP-RT, p=0.20). There was one late grade 2 GI toxicity (diarrhea) present at 37 months follow-up and 4 patients with late grade 2 GU toxicity. No grade 3 or higher late toxicity was recorded. Disease recurrence was noted in 3 patients with 1 death attributable to PCa. One patient died due to heart failure without recurrence at 17.5 months post treatment.
Conclusion: Extended lymph node proton irradiation is feasible. The acute grade 2+ GI toxicity rate of only 5% in this study compares favorably to contemporary photon-based trials. Further evaluation of extended lymph node irradiation in high risk PCa is warranted.