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Recurrent high-grade intracranial malignancies have a grim prognosis and uniform management guidelines are lacking. Re-irradiation is underused due to concerns about irreversible side effects. Pulsed-reduced dose rate radiotherapy (PRDR) aims to reduce toxicity while improving tumor control by exploiting dose-rate effects. We share our initial experience with temporally modulated pulsed proton re-irradiation (TMPPR), focusing on workflow, safety, feasibility, and outcomes for the first patient cohort. TMPPR was administered to patients with recurrent or progressive central nervous system malignancies using intensity modulated proton therapy with three fields. Patient and treatment data were collected, responses categorized using RANO assessment, and toxicities graded using CTCAE v5.0. Five patients received TMPPR between October 2022 and May 2023, with a median age of 54 years (Range: 32-72), and a median time from initial radiotherapy to re-RT of 23 months (Range 14-40). Treatment was completed without delay, with a median dose of 60 GyRBE in 30 fractions. Initial treatment response assessment showed complete (n = 1) or partial (n = 3) responses. Limited toxicity was observed, primarily grade 2 alopecia and one case of radiation necrosis graded at 2. This early experience demonstrates the feasibility of TMPPR delivery, highlighting the importance of prospective evaluations in the re-irradiation setting., (© 2024. The Author(s).)

Purpose: To provide a methodology for characterization of the technical properties of a newly developed non-metallic tissue expander for intensity modulated proton therapy., Methods: Three tissue expanders (AlloX2-Pro: plastic-dual port, AlloX2: metal-dual port, and Dermaspan: metal-single port) were deconstructed, CT-scanned, and modeled in RayStation12A. A 165 MeV single spot was used to create RayStation dose planes, and the integrated depth dose profiles were calculated and the DR90 extracted to predict water equivalent thickness (WET). These predictions were compared to measurements taken with an IBA Giraffe MLIC. Native, water, and fully modelled overrides were compared for the AlloX2 Pro to quantify differences in override choices. Geometric considerations between expanders were compared using a ray-tracing technique to contour the "no-fly" zone around metallic components using a clinical, three beam arrangement. Lastly, a planning and evaluation framework was provided using a single plan as an illustration., Results: The measured AlloX2-Pro WET values were within 0.22 cm of RayStation predictions while metallic values ranged from 0.08 to 0.46 cm. Using natively scanned density values for the AlloX2 Pro improved the discrepancy in WET between predicted and measured from -0.22 to -0.09 cm (drain) and from -0.17 to -0.12 cm (injection). The "no-fly" zone volume of all three beams reduced 95% between the AlloX2-Pro and Dermaspan, which geometrically allowed more uniform coverage behind the port and reduced need for beam modulation., Conclusion: The beam perturbation of the AlloX2-Pro is well modeled, but improved agreement with measured WET values was observed when utilizing native densities in calculations. The AlloX2 Pro can support beam arrangements that traverse the ports, which can enable simpler beam geometry and a reduction in dose modulation around the port to promote improved robustness and treatment delivery quality., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Introduction: Stereotactic radiosurgery (SRS) is highly conformal, high-dose radiation therapy delivered in 1-5 fractions, and is considered the standard of care for several central nervous system (CNS) indications. Particle therapies, such as protons, have physical and dosimetric advantageous properties compared to photons. However, proton SRS (PSRS) is not widely performed given the few particle therapy facilities, high-cost, and limited outcomes research as a sole modality and in comparative studies. The data available differs from each pathology. For AVMs, especially those with deep or eloquent locations, PSRS obliteration rates outcomes appear favorable and superior. For meningiomas, PSRS has been used for grade 1 alone, and for higher grades a PSRS boost has been considered. For vestibular schwannoma, PSRS seems to have favorable control rates with modest toxicity outcomes. For pituitary tumors, data shows excellent results with PSRS for functional and non-functioning adenomas. For brain metastasis, moderate doses of PSRS achieves high local control rates with low rates of radiation necrosis. For uveal melanoma, dedicated eyeline PSRS (4-5 fractions) are associated with very high tumor control and eye retention rates., Conclusions: PSRS is effective and safe for various intracranial pathologies. Limited data, usually retrospective and single institution series exist. There are numerous advantages of protons over photons, so it is important to understand limitations with further studies. Published clinical outcomes and widespread adoption of proton therapy will be key to unlocking the potential benefits of PSRS., Competing Interests: None

Purpose: To compare spatially fractionated radiation therapy (GRID) treatment planning techniques using proton pencil-beam-scanning (PBS) and photon therapy., Materials and Methods: PBS and volumetric modulated arc therapy (VMAT) GRID plans were retrospectively generated for 5 patients with bulky tumors. GRID targets were arranged along the long axis of the gross tumor, spaced 2 and 3 cm apart, and treated with a prescription of 18 Gy. PBS plans used 2- to 3-beam multiple-field optimization with robustness evaluation. Dosimetric parameters including peak-to-edge ratio (PEDR), ratio of dose to 90% of the valley to dose to 10% of the peak VPDR(D90/D10), and volume of normal tissue receiving at least 5 Gy (V5) and 10 Gy (V10) were calculated. The peak-to-valley dose ratio (PVDR), VPDR(D90/D10), and organ-at-risk doses were prospectively assessed in 2 patients undergoing PBS-GRID with pretreatment quality assurance computed tomography (QACT) scans., Results: PBS and VMAT GRID plans were generated for 5 patients with bulky tumors. Gross tumor volume values ranged from 826 to 1468 cm 3 . Peak-to-edge ratio for PBS was higher than for VMAT for both spacing scenarios (2-cm spacing, P = .02; 3-cm spacing, P = .01). VPDR(D90/D10) for PBS was higher than for VMAT (2-cm spacing, P = .004; 3-cm spacing, P = .002). Normal tissue V5 was lower for PBS than for VMAT (2-cm spacing, P = .03; 3-cm spacing, P = .02). Normal tissue mean dose was lower with PBS than with VMAT (2-cm spacing, P = .03; 3-cm spacing, P = .02). Two patients treated using PBS GRID and assessed with pretreatment QACT scans demonstrated robust PVDR, VPDR(D90/D10), and organs-at-risk doses., Conclusions: The PEDR was significantly higher for PBS than VMAT plans, indicating lower target edge dose. Normal tissue mean dose was significantly lower with PBS than VMAT. PBS GRID may result in lower normal tissue dose compared with VMAT plans, allowing for further dose escalation in patients with bulky disease., Competing Interests: Conflict of Interest: The authors have no relevant conflicts of interest to report., (©Copyright 2022 The Author(s) 2023.)

Purpose: Regional nodal irradiation improves disease-free and distant disease-free survival in patients with high-risk breast cancer (BC). Trials demonstrating this used 2- or 3-dimensional conformal radiation therapy (2-dimensional or 3-dimensional [3D] conformal radiotherapy [CRT]) fields based on bony anatomy. Modern volumetric-modulated arc therapy (VMAT) and pencil beam scanning proton therapy (PBSPT) may underdose regional nodes (RNs) not contoured but covered by 3D CRT. Multiple atlases guide modern treatment planning. This study addresses the risk of underdosing when relying on published atlases and treating with 3D CRT, VMAT, and PBSPT., Methods and Materials: Targets per the Radiation Therapy Oncology Group (RTOG), European Society for Radiotherapy and Oncology (ESTRO), and Radiotherapy Comparative Effectiveness Consortium (RADCOMP) atlases were contoured on a representative patient CT scan. 3D CRT plans based on anatomic borders and VMAT and PBSPT plans for each set of target volumes were generated. Positron emission tomography/computed tomography (PET/CT) scans were reviewed. CT-positive and 18 F-fluorodeoxyglucose ( 18 F-FDG)-avid RNs (n = 389) were mapped from 102 patients with locally advanced (n = 51; median 2; range, 1-8 nodes) and metastatic (n = 51; median 4; range, 1-19 nodes) BC: axillary (AX; n = 284), supraclavicular (SCV; n = 60), and internal mammary nodal (IMN; n = 45). 18 F-FDG-avid RNs falling within the 95% isodose line were considered adequately covered., Results: 3D CRT plans provided excellent RN coverage. Low AX nodes were covered (≥99%) in all plans. Underdosing of 18 F-FDG-avid RNs falling in the high AX (78%-92%), SCV (52%-75%), and IMN (84%-89%) volumes was observed following the RTOG and ESTRO atlases for VMAT and PBSPT plans. Use of the RADCOMP atlas provided coverage of these areas (89%-100%) with slightly increased heart and lung doses. Atlas guided VMAT/PBSPT plans provided cumulative nodal coverage as follows: ESTRO (89%/88%), RTOG (93%/91%), and RADCOMP (98%/96%)., Conclusions: VMAT and PBSPT for regional nodal irradiation in patients with high-risk BC risks underdosage in the high AX, SCV, and IMN nodal regions unless comprehensive target delineation is performed., (Published by Elsevier Inc.)

Multicriteria optimization (MCO), a novel commercially available optimization method for IMRT and VMAT has the potential to improve treatment planning techniques and workflows. MCO allows planners and physicians to assess in real time the impact and tradeoffs between all clinical goals and organ constraints. We investigate the feasibility of a universal set of objectives and constraints for VMAT plans in different anatomical sites and the impact of involving the Physician in the navigation of the generated Pareto plans. We randomly selected 20 prostate only, 14 whole pelvis, 10 advanced lung, 15 pancreas, and 7 head and neck plans planned with a VMAT technique. Using the clinically delivered isocenter and beam set-up, we retrospectively generated MCO plans with a universal set of constraints and objectives for each anatomical site. The MCO plan scores were compared with clinical plans or an independent plan generated with DMPO. For prostate only plans the TCP values for the clinical and MCO plans were similar and the rectum NTCP values and overall P+ were slightly better for the MCO plans. For whole pelvis, the resulting MCO plans were comparable in all the dosimetric measures to the clinical plans. For lung, the MCO dosimetric comparison also yielded comparable plans but when evaluating individual patients, there were 5 patients for which MCO plans had a clear advantage in reducing dose to lung and/or esophagus while improving/maintaining target coverage, 4 patients with comparable plans and 1 patient where MCO was worse. Allowing the physician to navigate independently produced a different selection of dosimetric trade-offs. Comparable MCO plans were also obtained for pancreas and head and neck. Based on our experience with many anatomical sites and a large number of patient plans, we have found that VMAT MCO plans are comparable to the clinical plans and can be produced with a universal set of objectives and constraints, even for a wide range of geometries and anatomies., (Copyright © 2019 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: Whole pelvis radiation therapy (WPRT) in premenopausal women with cervical cancer can cause permanent ovarian damage, resulting in premature menopause. Oophoropexy, often considered as an initial step, demonstrates safety of sparing 1 ovary at the cost of delay in initiating WPRT. Therefore, we dosimetrically compared volumetric modulated arc radiotherapy (VMAT) and intensity modulated proton therapy (IMPT) techniques to allow for ovarian-sparing WPRT., Materials and Methods: Ten patients previously treated for cervical cancer at our institution were included in this institutional review board-approved analysis. A modified clinical treatment volume (CTV) was designed, sparing 1 ovary (left or right), as determined by the physician (ovarian-sparing CTV) and disease extent, including physical exam, positron emission tomography/computed tomography and magnetic resonance imaging. An ovarian-sparing planning target volume was determined as the ovarian-sparing CTV+5 mm for patients who were supine and 7 mm for those who were prone. All plans were calculated to a dose of 45 Gy with specific optimization goals for target volumes, while attempting to maintain a mean ovary dose (D mean ) < 15 Gy. Dosimetric goals were compared across the 2 modalities using the Mann-Whitney U test., Results: Both treatment modalities were able to achieve primary clinical goal coverage to the uterus/cervix ( P = .529, comparing VMAT versus IMPT), ovarian-sparing CTV ( P = .796) and ovarian-sparing planning target volume ( P = .004). All 10 IMPT plans were able to accomplish the ovary objective (14.0 ± 1.66 Gy). However, only 4 of the 10 VMAT plans were able to achieve a D mean  < 15 Gy to the prioritized ovary, with an average dose of 15.3 ± 4.10 Gy., Conclusion: Sparing an ovary in women undergoing WPRT for cervical cancer is dosimetrically feasible with IMPT without sacrificing coverage to important clinical targets. Future work will incorporate the brachytherapy dose to the ovarian-sparing CTV and assess the clinical response of this technique as a means to preserve ovarian endocrine function., Competing Interests: Conflicts of Interest: The authors have no relevant conflicts of interest to disclose., (©Copyright 2019 The Author(s).)