Purpose To evaluate efficacy and toxicity (CTCAE v4.0) outcomes in patients with adenoid cystic carcinoma (ACC) treated with proton beam therapy (PBT). Patients and Methods From 2012 through 2023, 79 patients with non-metastatic ACC were treated with PBT and enrolled on the Proton Collaborative Group (PCG) registry. Kaplan-Meier analyses quantified locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). ACC patients receiving reirradiation with PBT were excluded from this analysis. Results Median follow-up was 3 years (0.01-6.72). Twenty-six patients were unable to undergo surgery and received definitive PBT versus postoperative PBT (n=53). Median postoperative PBT dose was 66 GyE and 70 GyE for definitive patients treated with conventional fractionation. Most patients had localized disease (n=75); few had nodal metastases (n=4). 62% were locally advanced (T3-T4) at the time of PBT treatment.3-year Locoregional control (LRC) for all patients was 98% [95% CI (94.3, 100)]. Advanced T-staging, positive margins and definitive-intent PBT were not associated with worsened LRC. 3-year Progression free survival (PFS) was 80.5% (70.6, 91.7). Patients receiving definitive intent PBT had lower but nonsignificant PFS (73.3% vs. 83.8%, p-0.075). Advanced T-staging and positive margins did not have worsened PFS. Overall survival at 3 years was 89.2% (81.4, 97.8).Acute grade 3 toxicities occurred in 16 patients, the most common included the following: mucositis (n=5), oral pain (n=3), and dermatitis (n=5). Late grade 3 toxicity (n=2) included middle ear inflammation (n=1) and skin ulceration (n=1). There were no grade 4+ toxicities. Conclusion PBT appears to be highly efficacious in providing LRC for patients with ACC including those patients treated with definitive intent. PBT toxicity was acceptable. Longer follow-up is needed.
Objective.Proton LATTICE radiotherapy (LRT), a form of spatially fractionated radiotherapy (SFRT), delivers a high dose to intratumoral vertices while maintaining low valley dose. Single-field optimization (SFO) is robust for preserving peak-to-valley patterns but results in a high entrance dose. Prior evidence suggests that smaller, more closely spaced high-dose regions may improve the therapeutic ratio. In this work, we propose aperture-collimated proton LRT (AC-LATTICE), which reshapes SFO proton LATTICE fields into narrow GRID-like entrance beamlets to reduce entrance dose while preserving vertex coverage, spatial modulation, and robustness.Approach. A multi-field, geometry-constrained semi-face-centered-cubic vertex optimization framework was developed to generate non-overlapping intratumoral vertices (4.4 mm diameter; minimum 3D spacing 1.4 ± 0.2 cm) and map each vertex to a deliverable GRID beamlet with minimal geometric error under spacing/clearance constraints. A fixed GRID entrance pattern was imposed in beam's-eye view (1.0 cm hole pitch; 5 mm openings); this two-dimensional pitch defines aperture-plane sampling and is distinct from the achieved 3D vertex spacing after feasibility constraints. Proton AC-LATTICE plans were retrospectively created in RayStation v2023B for eight DIBH primary liver cancer patients (mean GTV 89.7 cc; range 57.6-160.6 cc) following consensus guidance. Prescription was 18 Gy per vertex and 3 Gy to GTV using SFO. Metrics included GTVD95%, Dmean, gEUD (a= - 10), PVDR (D2%/D50%), skinD1%, and liver-GTVDmean. Robustness evaluations used 3.5% range and 5 mm setup uncertainties (second-worst-case), with CBCT-based analysis across the course. Statistical comparisons were performed using a two-sided paired t-test.Main results. AC-LATTICE preserved spatial modulation (PVDR ⩾3.5) across dosimetric analyses while maintaining stable target and normal-tissue metrics. Nominal plans achieved PVDR 3.6 ± 0.4, GTVD95%3.1 ± 0.08 Gy, GTVDmean5.8 ± 0.6 Gy, gEUD 3.5 ± 0.1 Gy, liver-GTVDmean0.9 ± 0.3 Gy, and skinD1%1.4 ± 0.6 Gy. PVDR decreased to 3.3 ± 0.4 in the robust second-worst-case scenario (p< 0.05), with average changes of 1.7%, 5.8%, and 2.8% in GTVD95%,Dmeanand gEUD (p< 0.05). CBCT evaluation maintained PVDR (3.6 ± 0.6 on the first CBCT; 3.5 ± 0.6 on the last CBCT), with no meaningful degradation in other metrics. For the end-to-end test using a head-and-neck phantom, the gamma passing rate was 99% using 2%/2 mm criteria.Significance and conclusion. AC-LATTICE is a compact, robust, and clinically feasible proton LRT delivery strategy that maintains robust spatial fractionation under treatment uncertainties and anatomical variation, supporting broader applicability of proton SFRT when the entrance dose is of concern. This compact approach may extend SFRT to more patients, including those with smaller or difficult-to-treat targets.
PURPOSE:Recent national policies have championed new standards in family and medical leave for graduate medical trainees. We hypothesize there remains variability in residency program leave policies. Project PARENT aimed to create a database of parental leave policies at US radiation oncology and medical physics residency programs. METHODS AND MATERIALS:A mixed methods design was used in this study. A 29-question survey was distributed in 2024 to all US radiation oncology physician (RO) and medical physics (MP) residency programs by email and remained open for 6 weeks. For programs that did not supply a survey response, document analysis (data abstraction) was performed with information from program websites. All programs were offered a data verification opportunity. RESULTS:The survey was distributed to 84 US RO, 107 MP therapy, and 43 MP imaging residency programs. Composite survey responses were completed by 32 of 84 (38%) physician residencies and 75 of 100 (50%) MP programs (62 therapy + 13 imaging). Altogether, website data abstraction for programs without responses resulted in a final program representation of 99% and 100% in RO and MP programs, respectively. Among programs who provided a specific value, the median 'maximum parental leave' provided was 12 weeks (IQR, 8-12) for RO birthing parents, 12 weeks (IQR, 12-12) for MP birthing parents, 12 weeks (IQR, 6-12) for RO non-birthing parents, and 12 weeks (IQR, 8-12) for MP non-birthing parents; the median length of paid leave provided to all parents in RO and MP residency programs was 6 weeks. CONCLUSIONS:Project PARENT is the first comprehensive parental leave information source in any medical specialty. We anticipate this family leave program policy database will empower residency program leaders and applicants to navigate family leave policies to the mutual benefit of all.
Tumor-infiltrating lymphocyte (TIL) therapy is an emerging option for treatment-refractory melanoma. Studies for TIL therapy approval excluded patients with uncontrolled melanoma brain metastases (MBMs). Given the timeline from TIL harvest to infusion and use of lymphodepletion there are concerns about intralesional hemorrhage, intracranial progression and toxicity. There are limited data on management of MBMs during the peri-TIL therapy window and the safety/efficacy of integrating radiotherapy (RT). We performed a retrospective analysis of patients with advanced melanoma that underwent TIL harvest at a single institution from May to December 2024 with attention to clinical outcomes, RT parameters and adverse events (CTCAEv5.0) related to TIL therapy or RT. Patients with MBMs were stratified by receipt of RT and timing of development of MBMs relative to TIL harvest. 9 patients with MBMs and undergoing TIL harvest were identified. Median time from TIL harvest to infusion was 2.1mo and median follow-up post-harvest was 4.4mo. Two patients had known MBMs and underwent RT >3mo prior to TIL harvest. 55% (5 of 9) of patients developed new MBMs during the window from TIL harvest to infusion. 67% (6 of 9 patients) underwent brain-directed RT. Of note, 50% of patients that underwent RT had evidence of possible intralesional bleed noted on brain MRI prior to RT. RT-related toxicity was minimal with grade 1-2 fatigue, grade 1 headaches and no radiographic or symptomatic radiation necrosis. There were no intracranial bleeding events after TIL harvest. Extracranial, regional brain and irradiated/local control was 44%, 67%, 83%, respectively. Our experience suggests that treatment of MBMs with RT in patients undergoing TIL therapy is feasible and safe. Given the risk of intracranial progression or development of new MBMs between TIL harvest and infusion, RT is an option as a consolidative ‘bridging’ therapy for intracranial disease control.
