The aim of this study was to assess the clinical outcome, including QoL, of patients with intracranial meningiomas WHO grade 1–3 who were treated with Pencil Beam Scanning Proton Therapy (PBS PT) between 1997 and 2022. Two hundred patients (median age 50.4 years, 70% WHO grade 1) were analyzed. Acute and late side effects were classified according to CTCAE version 5.0. Time to event data were calculated. QoL was assessed descriptively by the EORTC-QLQ-C30 and BN20 questionnaires. With a median follow-up of 65 months (range: 3.8–260.8 months) the 5 year OS was 95.7% and 81.8% for WHO grade 1 and grade 2/3, respectively (p < 0.001). Twenty (10%) local failures were observed. Failures occurred significantly (p < 0.001) more frequent in WHO grade 2 or 3 meningioma (WHO grade 1: n = 7, WHO grade 2/3: n = 13), in patients with multiple meningiomas (p = 0.005), in male patients (p = 0.005), and when PT was initiated not as upfront therapy (p = 0.011). There were no high-grade toxicities in the majority (n = 176; 88%) of patients. QoL was assessed for 83 (41.5%) patients and for those patients PT did not impacted QoL negatively during the follow-up. In summary, we observed very few local recurrences of meningiomas after PBS PT, a stable QoL, and a low rate of high-grade toxicity.

Background: Moderate hyperthermia is a potent and evidence-based radiosensitizer. Several indications are reimbursed for the combination of deep hyperthermia with radiotherapy (dHT+RT). We evaluated the current practice of dHT+RT in Switzerland. Methods: All indications presented to the national hyperthermia tumor board for dHT between January 2017 and June 2021 were evaluated and treatment schedules were analyzed using descriptive statistics. Results: Of 183 patients presented at the hyperthermia tumor board, 71.6% were accepted and 54.1% (99/183) finally received dHT. The most commonly reimbursed dHT indications were “local recurrence and compression” (20%), rectal (14.7%) and bladder (13.7%) cancer, respectively. For 25.3% of patients, an individual request for insurance cover was necessary. 47.4% of patients were treated with curative intent; 36.8% were in-house patients and 63.2% were referred from other hospitals. Conclusions: Approximately two thirds of patients were referred for dHT+RT from external hospitals, indicating a general demand for dHT in Switzerland. The patterns of care were diverse with respect to treatment indication. To the best of our knowledge, this study shows for the first time the pattern of care in a national cohort treated with dHT+RT. This insight will serve as the basis for a national strategy to evaluate and expand the evidence for dHT.

Purpose: The purpose of this study was to report the clinical and patient-reported outcomes of children and adolescents with intracranial meningioma treated with pencil beam scanning proton therapy (PBS-PT). Material and methods: Out of a total cohort of 207 intracranial meningioma patients treated with PBS-PT between 1999 and 2022, 10 (4.8%) were children or adolescents aged < 18 years. Median age was 13.9 years (range, 3.2–17.2). Six (60%) children were treated as primary treatment (postoperative PT, n = 4; exclusive PT, n = 2) and four (40%) at the time of tumor recurrence. Acute and late toxicities were registered according to Common Terminology Criteria of Adverse Events (CTCAE). Quality of life (QoL) before PBS-PT was assessed using PEDQOL questionnaires. Educational, functional, and social aspects after PT were assessed through our in-house developed follow-up surveys. Median follow-up time was 71.1 months (range, 2.5–249.7), and median time to last questionnaire available was 37.6 months (range, 5.75–112.6). Results: Five (50%) children developed local failure (LF) at a median time of 32.4 months (range, 17.7–55.4) after PBS-PT and four (80%) were considered in-field. One patient died of T-cell lymphoma 127.1 months after PBS-PT. Estimated 5-year local control (LC) and overall survival (OS) rates were 19.4% and 100.0%, respectively. Except for one patient who developed a cataract requiring surgery, no grade ≥3 late toxicities were reported. Before PT, patients rated their QoL lower than their parents in most domains. During the first year after PT, one child required educational support, one needed to attend to a special school, one had social problems and another three children required assistance for daily basic activities (DBA). Three years after PT, only one child required assistance for DBA. Conclusions: The outcome of children with intracranial meningioma treated with PBS-PT is in line with other centers who have reported results of radiation therapy delivered to this particular patient group. This therapy provides acceptable functional status profiles with no high-grade adverse radiation-induced events.

PURPOSE: Circulating tumor DNA (ctDNA) holds promise for prognostication and disease monitoring in solid tumors. However, rare and heterogenous tumors with low mutational burden like soft tissue sarcomas (STS) present a technical challenge for ctDNA analysis. We investigated the ability of personalized ctDNA analysis to predict outcomes and track response to radiotherapy and pembrolizumab in patients with localized STS. METHODS: We analyzed 313 plasma samples collected pretreatment, postradiotherapy/presurgery, and postsurgery from 106 patients treated with preoperative radiotherapy with or without perioperative pembrolizumab for high-risk, localized STS in the SU2C-SARC032 phase II randomized trial. Personalized ctDNA assays were designed to track a median of 46 somatic mutations per patient. Associations between ctDNA levels and outcomes were assessed using univariable and multivariable models adjusting for clinical risk factors. RESULTS: Personalized ctDNA profiling detected baseline ctDNA in 85% of patients. Baseline ctDNA levels correlated with tumor size, grade 3 disease, and expression of genes related to hypoxia and the cell cycle. ctDNA levels pretreatment, after radiotherapy with or without immunotherapy but before surgery, and postsurgery were strongly associated with disease-free and overall survival on univariable and multivariable analyses. Patients treated with pembrolizumab, who had significantly better disease-free survival, had a greater decrease in their ctDNA levels after neoadjuvant therapy. Finally, personalized ctDNA analysis enabled noninvasive subclone tracking and patients with multiple tumor clones detected by ctDNA analysis after surgery had inferior outcomes. CONCLUSION: Tumor-informed, personalized profiling enables sensitive ctDNA detection and quantitative monitoring in localized STS, providing independent prognostic information across the perioperative course. These findings support prospective ctDNA-guided interventional trials in STS.

Radiotherapy (RT) combined with surgery is standard of care for most soft tissue sarcoma (STS) of the extremity and trunk. Preoperative RT is often preferred because it enables a lower radiation dose and is associated with more favorable late toxicity profiles. We report real-world, long-term oncological, toxicity, and functional outcomes of patients treated with preoperative RT at a sarcoma reference center. We did a retrospective analysis of data from our prospectively maintained database (data collected from April 1989 to November 2020) from a single sarcoma center in Canada. We included patients with histologically confirmed STS of extremity or trunk. Eligible patients received preoperative RT with either 2D/3D-Conformal Radiation Therapy (3D-CRT) or Intensity Modulated Radiation Therapy (IMRT), followed by surgery 4–6 weeks later. Local and oncological outcomes were assessed. Long-term toxicities were graded using the RTOG late toxicity scoring criteria. The Musculoskeletal Tumor Society Rating Scale (MSTS) and Toronto Extremity Salvage Score (TESS) evaluated functional outcomes. Further study endpoints included the occurrence of distant metastases (DM) and overall survival (OS), stratified by histology. Among 1027 patients (370 3D-CRT, 657 IMRT), the median follow-up was 5.9 years (range: 0.5–24.6 years). Major wound complications occurred in 28% with 3D-CRT and in 21% with IMRT (p = 0.09). The 5-year cumulative rates of local recurrence (LR) and distant metastasis were 5.2% vs. 5.4% and 25.5% vs. 25.6%, with a 5-year overall survival of 79.3%. None of these outcomes differed significantly between 3D-CRT and IMRT. Grade ≥2 late toxicity occurred in 25% (30% in 3D-CRT and 22% in IMRT), including fibrosis (17%), skin toxicity (9%), joint stiffness (6%), and edema (9%). IMRT was associated with significantly lower rates of grade ≥2 skin toxicity (OR 0.28), subcutaneous fibrosis (OR 0.55), and joint stiffness (OR 0.49) compared to 3D-CRT. Functional outcomes were comparable between IMRT and 3D-CRT. Patients with grade ≥2 toxicities had lower functional scores (p < 0.001). In this large cohort with mature follow-up, long-term local control and function were excellent with low rates of high-grade toxicity. Modern RT techniques were associated with less late toxicity without compromising local control, but acute wound complications and distant metastases remain ongoing challenges. None.