Setting the Stage: Feasibility and Baseline Characteristics in the PARTIQoL Trial Comparing Proton Therapy vs. IMRT for Localized Prostate Cancer.

PURPOSE/OBJECTIVES: Men with localized prostate cancer may receive either photon-based intensity-modulated radiotherapy (IMRT) or proton beam therapy (PBT). The XXXXX trial (NCT01617161), demonstrates the feasibility of performing a large, multicenter phase 3 randomized trial comparing IMRT to PBT for localized prostate cancer. Here, we report baseline features of patients enrolled on this trial and present strategies to improve feasibility of other similar trials. MATERIALS/METHODS: Patients with low- or intermediate-risk prostate cancer were randomized to either PBT or IMRT with stratification by institution, age, use of rectal spacer, and fractionation schedule (conventional fractionation: 79.2 Gy in 44 fractions vs. moderate hypofractionation: 70.0 Gy in 28 fractions). The primary endpoint is a change from baseline bowel health using the EPIC score 24 months after radiotherapy. Secondary objectives include treatment-related differences in urinary and erectile functions, adverse events, and efficacy endpoints. RESULTS: Between 07/2012 and 11/2021, 450 patients were successfully accrued. Patients were randomized to either PBT (N=226) or to IMRT (N=224); 13 were ineligible or withdrew prior to treatment. The median age of 437 analyzed patients was 68 years (range 46-89). 41% of patients had low-risk and 59% had intermediate-risk disease. 49% of patients were treated with conventional fractionation and 51% with moderately hypofractionation. For patients receiving PBT, 48% used a rectal balloon, 44% a rectal spacer, and 5% both. For patients receiving IMRT, 46% used a rectal balloon, 42% a rectal spacer, and 5% both. PBT and IMRT arms were balanced for baseline variables. CONCLUSIONS: Despite significant challenges, the XXXXX trial demonstrated that, with targeted recruitment approaches, multicenter collaboration, payer engagement, and protocol updates to incorporate contemporary techniques, it is feasible to perform a large phase III randomized clinical trial to assess whether PBT improves outcomes. We will separately report primary results and continue to monitor participants for longer followup and secondary endpoints.

Quality of life and clinical outcomes in rectal cancer patients treated on a 1.5T MR-Linac within the MOMENTUM study.

Background and purpose: This study assessed quality of life (QoL) and clinical outcomes in rectal cancer patients treated with magnetic resonance (MR) guided short-course radiation therapy (SCRT) on a 1.5 Tesla (T) MR-Linac during the first 12 months after treatment. Materials and methods: Rectal cancer patients treated with 25 Gy SCRT in five fractions with curative intent in the Netherlands (2019-2022) were identified in MOMENTUM (NCT04075305). Toxicity (CTCAE v5) and QoL (EORTC QLQ-C30 and -CR29) was primarily analyzed in patients without metastatic disease (M0) and no other therapies after SCRT. Patients who underwent tumor resection were censored from surgery. A generalized linear mixed-model was used to investigate clinically meaningful (≥10) and significant (P < 0.05) QoL changes. Clinical and pathological complete response (cCR and pCR) rates were calculated in patients in whom response was documented. Results: A total of 172 patients were included, of whom 112 patients were primarily analyzed. Acute and late radiation-induced high-grade toxicity were reported in one patient, respectively. CCR was observed in 8/64 patients (13 %), 14/37 patients (38 %) and 13/16 patients (91 %) at three, six and twelve months; pCR was observed in 3/69 (4 %) patients. After 12 months, diarrhea (mean difference [MD] -17.4 [95 % confidence interval [CI] -31.2 to -3.7]), blood and mucus in stool (MD -31.1 [95 % CI -46.4 to -15.8]), and anxiety (MD -22.4 [95 % CI -34.0 to -10.9]) were improved. Conclusion: High-field MR-guided SCRT for the treatment of patients with rectal cancer is associated with improved disease-related symptom management and functioning one year after treatment.

Use of high and very high dose radiotherapy after radical prostatectomy for prostate cancer in the United States.

BACKGROUND: The cost-benefit tradeoff of radiation dose-intensification for prostate cancer in the post-prostatectomy setting is difficult to predict and is ideally studied in randomized trials. The purpose of this study was to assess the use of dose-escalated post-operative radiation (PORT) for prostate cancer in the United States, during a period in which there were no published level 1 studies on dose-escalation. METHODS: We performed analyses on pT2-3, N0, M0 prostate cancer patients who received PORT after an R0-1 resection within the National Cancer Data Base (NCDB), 2003-2012. We classified patients according to the use of high dose (>66.60 cGy) and very high dose (>70.20 cGy) radiation. We used regression analysis to assess the association of year of treatment with use of high and very high dose PORT. To demonstrate the potential of a registry-based network like the NCDB to prospectively monitor changes in radiation dosing patterns, we determined the year in which a significant change in dose could have been first detected had dose been actively monitored. RESULTS: Between 2003 and 2012, the use of high dose PORT increased from 29.9% CI (26.7-33.1) to 63.5% CI (60.6-66.5) and very high dose PORT from 4.5% CI (3.1-5.9) to 10.8% CI (8.9-12.6) (adjusted p < 0.01, for both trends). Patients diagnosed at community centers were less likely to be treated with high dose PORT compared to those at academic or comprehensive centers (p < 0.01 for both comparisons). Had the NCDB network been prospectively monitoring PORT dose, significant increases in dose would have been detected as early as 2004 and after every year of the study period. CONCLUSIONS: The use of both high dose and very high dose PORT increased two-fold from 2003 to 2012 in the absence of randomized studies. This change in practice may be exposing patients to excess toxicity without cancer control benefits. Monitoring dosing patterns using cancer registries is feasible.

Brain-sparing total meningeal radiation for a patient with widespread progressive meningiomas using helical intensity modulated radiation.

Multiple meningioma is a rare but difficult clinical entity. We describe the case of a patient with widespread progressive meningiomas who could not safely have surgery or radiosurgery. We have previously treated these patients with whole brain radiation, despite the risks of neuropsychological side effects. In this case, we treated with a novel use of helical intensity modulated radiation therapy: brain-sparing total meningeal radiation. The brain-sparing technique allowed us to treat the patient's meninges with higher doses than would have been possible with whole brain radiation and with the goal of achieving long-term disease control.