Phase I Trial of Pelvic Nodal Dose Escalation With Hypofractionated IMRT for High-Risk Prostate Cancer

Abstract

Purpose Toxicity concerns have limited pelvic nodal prescriptions to doses that may be suboptimal for controlling microscopic disease. In a prospective trial, we tested whether image-guided IMRT can safely deliver escalated nodal doses while treating the prostate with hypofractionated radiotherapy in 5–1/2 weeks. Methods and Materials Pelvic nodal and prostatic image-guided IMRT was delivered to 53 NCCN high risk patients to a nodal dose of 56 Gy in 2 Gy fractions with concomitant treatment of the prostate to 70 Gy in 28 fractions of 2.5 Gy, and 50 of 53 patients received androgen deprivation for a median duration of 12 months. Results The median follow-up was 25.4 months (range 4.2–57.2). No early grade 3 (Gr3) RTOG or CTCAE v.3.0 GU or GI toxicities were seen. The cumulative actuarial incidence of Gr2 early GU toxicity (primarily alpha blocker initiation) was 38%. The rate was 32% for Gr2 early GI toxicity. None of the dose-volume descriptors correlated with GU toxicity, and only the volume of bowel receiving ≥30 Gy correlated with early GI toxicity (p=0.029). Maximum late grades 1,2 and 3 GU toxicities were seen in in 30%, 25% and 2%, respectively. Maximum late grade 1 and 2 GI toxicities were seen in 30% and 8% (rectal bleeding requiring cautery), respectively. The estimated 3-year biochemical control (nadir + 2) was 81.2 ± 6.6%. No patient manifested pelvic nodal failure, while two experienced para-aortic nodal failure outside the field. The 6 other clinical failures were distant only. Conclusions Pelvic IMRT nodal dose escalation to 56 Gy was delivered concurrently with 70 Gy of hypofractionated prostate radiotherapy in a convenient, resource-efficient and well-tolerated 28 fraction schedule. Pelvic nodal dose escalation may be an option in any future exploration of potential benefits of pelvic radiation therapy in high-risk prostate cancer patients.

Late Toxicity and Outcomes in High-risk Prostate Cancer Patients Treated With Hypofractionated IMRT and Long-term Androgen Suppression Treatment

“…Nevertheless, these nonrandomized studies for highrisk prostate cancer currently support the use of HFRT with AST to the prostate and PLN, with the absence of severe GI or GU toxicity reported to date. 8,[19][20][21][22] The length of follow-up, 60 months, strengthens the late toxicity reported from our current study, with comparable results to those demonstrated by Quon et al 22 with a follow-up of 40 months, and similar EQD2 of 81 versus 82 Gy in the present study. As highlighted in the present study, late toxicity at 5 years for GU toxicity was seen in 1 patient (2.44%) experiencing grade 3 and no patients experiencing G3 toxicity at 5 years, in comparison with 0% and 4% for GI and GU toxicity ZG3 in the study by Quon et al 22 Despite the heterogeneity within HFRT technical aspects in current trials, there is mounting evidence to the benefits of HFRT.…”

“…In addition, with a median follow-up of 63 months (range, 7 to 80 mo), late toxicity reporting is strengthened allowing comparison with other studies reporting outcome of HFRT for prostate cancer. 11,14,15 Increasing the strength of the study is the consistent use of TomoTherapy IMRT for all patients, in contrast to other studies utilizing both 2D RT and 3DCRT 7,14 ; nevertheless, multiple trials using conformal RT (Tomotherapy, SIB IMRT) have been published [19][20][21][22]27 but few of these studies have reported late toxicity and outcomes with adequate follow-up intervals.…”

Hypofractionated simultaneous integrated boost (IMRT-SIB) with pelvic nodal irradiation and concurrent androgen deprivation therapy for high-risk prostate cancer: results of a prospective phase II trial

“…The lower rates of side effects that we observed, compared to the prospective studies reporting late toxicity of prostate hypofractionation combined with WPRT [30][31][32] were likely attributed to the robustness of our planning (in terms of severe DVH constraints for OARs and quality of dose distribution), to an accurate daily preparation phase of the patients to minimize the impact of the organ movement and to permit a reliable on-line IGRT strategy.…”

“…Concerning the secondary end point, the good results compared to the prospective studies regarding high-risk prostate patients treated with ADT and IMRT-SIB [30][31][32] might have been related to the adequacy of pelvic LN coverage, as explained by Spratt et al [4]. Although encouraging results need to be interpreted with caution due to the design of our investigation.…”

A Systematic Review of Hypofractionation for Primary Management of Prostate Cancer

“…Small bowel, often abutting the nodal regions at risk for metastatic spread, is relatively sensitive to dose and fraction size and thus prevents hypofractionation of a nodal treatment plan. Several phase 2 studies have treated pelvic lymph nodes in high-risk patients using a simultaneous integrated boost (SIB) technique, meaning that the pelvic region is treated at 1.8-2 Gy per day while the prostate receives 2.5-2.7 Gy during the same fraction [42][43][44]. These studies, which have included long-term ADT, have noted 3-to 4-yr biochemical control of 80 + % (median followup: 24-42 mo).…”