Stephen Greco

Background/Objectives: Limited data exists comparing photon-based intensity-modulated (IMRT) or volumetric modulated arc therapy (VMAT) against intensity-modulated proton therapy (IMPT) when treating pelvic or para-aortic nodal recurrences of prostate cancer following prior irradiation. The aim of this study was to evaluate dosimetric differences between VMAT and IMPT when treating nodal recurrences in the re-irradiation setting. Methods: VMAT and IMPT plans for 15 patients with node-recurrent disease were evaluated. Prescription doses to the whole pelvis and prostate bed planning target volumes (PTVs) from the initial VMAT plans were 45–50.4 Gy and 66.6–72 Gy, respectively. IMPT re-irradiation prescription doses were 45–53.75 Gy radiobiological equivalent (GyE) (proton radiobiological effective dose 1.1) to at-risk pelvic and para-aortic nodal chains and 60–64 GyE to gross nodal disease. For re-planning and comparative study purposes, clinical target volume (CTV) prescription doses were standardized to 50.4 Gy for the regional pelvic and para-aortic nodes, and 63 Gy for the grossly involved nodal disease. Organ-at-risk (OAR) contours were standardized and re-irradiation plans were generated on Raystation. Student’s t-test was used to compare CTV coverage and dose to OARs. Results: CTV coverage was met for all plans, with 99% of CTVs receiving ≥99% of prescription doses. Composite analysis demonstrated IMPT not only sustained dosimetric benefits in the re-irradiation setting for all OARs except sigmoid but also conferred significant advantages. Select endpoints with significant differences on composite analysis included bowel cavity V45Gy, left kidney V18Gy and mean dose, right kidney V18Gy and mean dose, and integral dose to ‘Body-CTV’. Conclusions: Composite analysis of the initial treatment and re-irradiation plans showed that IMPT delivered and maintained significant OAR dose reductions in the nodal re-irradiation setting, potentially decreasing the risk of long-term toxicities. This provides a rationale for the utilization of IMPT in this clinical setting.

Delayed radiation-induced injuries generally manifest months to years after the completion of radiation therapy and can be challenging to diagnose and treat because of a paucity of evidence-based therapeutic options. Individuals who receive high doses of radiation therapy are more likely to experience delayed radiation injuries, but those who receive relatively low radiation doses may also rarely develop this condition. We present the case of a patient who developed delayed radiation-induced enteritis several weeks after receiving low-dose radiation therapy to the terminal ileum. The patient's signs and symptoms improved significantly after administration of hyperbaric oxygen therapy.

Multimodal therapies were combined to eradicate the primary site, metastatic, and micrometastatic disease in men with newly diagnosed, synchronous, oligometastatic prostate cancer. The investigation included companion, phase II studies: total eradication therapy-1 (TET-1) for those treatment-naïve and total eradication therapy-2 (TET-2) for those post-prostatectomy. The treatment-naive protocol included androgen deprivation and docetaxel (with concurrent abiraterone added in a protocol amendment), followed by a prostatectomy, adjuvant radiation (if positive margins, T3/4, or detectable PSA), and metastasis-directed therapy. The post-prostatectomy protocol assigned the same therapies (omitting the prostatectomy). The primary endpoint was an undetectable PSA with recovered testosterone. The safety boundaries were ≤ 50% for grade 3/4 neutropenic and ≤ 20% for grade 3/4 surgical- and radiation-related toxicities. Enrollment was planned for 60 patients per protocol, to detect a PSA progression-free survival ≥ 32%, as compared to 15% in a historic control. Enrollment closed early. An interim analysis was conducted once > 50% of patients were evaluable for the primary endpoint. The primary endpoint duration was assessed by median progression-free survival. 52 patients were enrolled (n = 26 per protocol). Medium follow-up was 30.3 months. 80% (24/30) of evaluable patients achieved the primary endpoint; the duration was not reached. Of those not evaluable, 77% (17/22) had not reached the endpoint and 23% (5/22) had exited. There were 8% (4/52) grade 3/4 neutropenic and 2% (1/48) grade 3/4 surgical or radiation-induced toxicities. Interim findings suggest the trials’ endpoints were met, advancing the concept of total eradication therapy in men with oligometastatic prostate cancer.

In men with a rising PSA following radical prostatectomy, salvage radiation therapy (SRT) offers a second chance for cure. Hormonal therapy can be combined with SRT in order to increase prostate tumor control, albeit with associated higher rates of treatment side effects. This trial studies the effectiveness of SRT combined with hormonal therapy using a more potent anti-androgen with a favorable side effect profile. Enzalutamide, a next generation selective androgen receptor antagonist, is approved by the Food and Drug Administration for the treatment of metastatic castrate-resistant prostate cancer (CRPC) where it has been shown to improve overall survival in combination with androgen deprivation therapy. The primary objective of this study is to evaluate the efficacy of combination SRT and enzalutamide for freedom-from-PSA-progression. Secondary objectives include time to local recurrence within the radiation field, metastasis-free survival and safety as determined by frequency and severity of adverse events. This is a randomized, double-blind, phase II, prospective, multicenter study in adult males with biochemically recurrent prostate cancer following radical prostatectomy. Following registration, enzalutamide 160 mg or placebo by mouth (PO) once daily will be administered for 6 months. Following two months of study drug, external beam radiotherapy to 66.6–70.2 Gray (Gy) will be administered to the prostate bed over 7–8 weeks while continuing daily placebo/enzalutamide. This is followed by two additional months of placebo/enzalutamide. The SALV-ENZA trial is the first phase II placebo-controlled double-blinded randomized study to test SRT in combination with a next generation androgen receptor antagonist in men with high-risk recurrent prostate cancer after radical prostatectomy. The primary hypothesis of this study is that clinical outcomes will be improved by the addition of enzalutamide compared to standard-of-care SRT alone and pave the path for phase III evaluation of this combination. ClinicaltTrials.gov Identifier: NCT02203695 Date of Registration: 06/16/2014. Date of First Participant Enrollment: 04/16/2015.