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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.

The aim of this analysis was to assess the early clinical results of pencil beam scanning proton therapy (PT) in the treatment of young children with non-metastatic atypical teratoid/rhabdoid tumor (ATRT) of the CNS. Fifteen children (male, n=8, 53%) were treated with PT between May 2008 and January 2013. Mean age at diagnosis was 17.4±7.0months. The localization was infratentorial in 9 (60%) patients. Gross total resection of the primary tumors was achieved in 7 (47%) patients. The dose administered focally under sedation was 54Gy (RBE). After a median follow-up of 33.4months (range 9.7-69.2), 3 (20%), 4 (27%) and 2 (13%) patients presented with local failure (LF), distant brain failure (DBF) and spinal failure (SF), respectively. Six patients died, all of tumor progression. The 2-year overall- and progression-free survival was 64.6 and 66.0%. Tumor location (supratentorial) and the extent of surgical resection (non-gross total resection) were negative prognostic factors for both OS and PFS. PT was well tolerated. No grade >2 acute toxicity was observed. The estimated 2-year toxicity-free survival was 90%. As assessed by the PedsQoL proxy, no decrease in QoL was observed after PT. We conclude that PBS PT is an effective treatment for young children with ATRT. After PT, with or without concomitant chemotherapy, two third of the patients survived >2years. Acute toxicity was manageable. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and treatment-induced toxicity.

We report on a comparative dosimetrical study between deep inspiration breath hold (DIBH) and shallow breathing (SB) in prone crawl position for photon and proton radiotherapy of whole breast (WB) and locoregional lymph node regions, including the internal mammary chain (LN_MI). We investigate the dosimetrical effects of DIBH in prone crawl position on organs-at-risk for both photon and proton plans. For each modality, we further estimate the effects of lung and heart doses on the mortality risks of different risk profiles of patients. Thirty-one patients with invasive carcinoma of the left breast and pathologically confirmed positive lymph node status were included in this study. DIBH significantly decreased dose to heart for photon and proton radiotherapy. DIBH also decreased lung doses for photons, while increased lung doses were observed using protons because the retracting heart is displaced by low-density lung tissue. For other organs-at-risk, DIBH resulted in significant dose reductions using photons while minor differences in dose deposition between DIBH and SB were observed using protons. In patients with high risks for cardiac and lung cancer mortality, average thirty-year mortality rates from radiotherapy-related cardiac injury and lung cancer were estimated at 3.12% (photon DIBH), 4.03% (photon SB), 1.80% (proton DIBH) and 1.66% (proton SB). The radiation-related mortality risk could not outweigh the ~ 8% disease-specific survival benefit of WB + LN_MI radiotherapy in any of the assessed treatments.

OBJECTIVE Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). METHODS: Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. RESULTS: Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369-1142). All patients completed PT and received a median of 5 HT sessions (range, 2-6). Median follow-up was 18 months (range, 9-26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9-72). All patients experienced acute Grade 2-3 local pain. One patient presented with a late Grade 3 iliac fracture. CONCLUSION Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. ADVANCES IN KNOWLEDGE: This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.

OBJECTIVE The aim of this paper was to evaluate the prognostic factors in surgical and adjuvant care for spinal chordomas and chondrosarcomas after surgery followed by high-dose pencil-beam scanning proton therapy (PBS-PT). METHODS From 1997 to 2016, 155 patients (61 female patients; median age 55 years) with spinal (cervical, n = 61; thoracic, n = 29; lumbar, n = 13; sacral, n = 46; pelvic, n = 6) classic chordomas (n = 116) and chondrosarcomas (n = 39; most were low grade) were treated with maximal safe resection followed by PBS-PT (median dose prescribed: 74 Gy [relative biological effectiveness], range 48.6-77 Gy). The majority of patients (n = 153, 98.7%) had undergone at least 1 resection prior to PBS-PT (median 1, range 0-5; biopsy only, n = 2). Fewer than half (45.1%) of the surgeries were rated as gross-total resections (GTRs) prior to PBS-PT. Surgical stabilization (SS) was present in 39% of all patients (n = 60). Ninety-one patients (59%) presented with macroscopic tumor at the start of PBS-PT. The median follow-up duration was 64.7 months (range 12.2-204.8 months). RESULTS The 5-year local tumor control, disease-free survival (DFS), and overall survival were 64.9% (95% CI 56.3%-73.5%), 59.4% (95% CI 50.6%-68.2%), and 77.9% (95% CI 70.6%-85.2%), respectively. In total, 63 patients (40.6%) experienced failure during the follow-up period: local only in 32 (20.6%), distal only in 7 (4.5%), local + distal in 19 (12.3%), surgical pathway failure (SPF) only in 2 (1.3%), local + SPF in 2 (1.3%), and distal + SPF in 1 (< 1%). Univariate analysis identified gross residual disease, the presence of SS, and treatment era prior to 2008 as highly significant for worse outcome, with all 3 remaining significant on multivariate analysis. The type of surgery (GTR or subtotal resection/biopsy) and whether GTR was achieved by en bloc or curettage did not show a significant prognostic effect. Surgical complications prior to PBS-PT were present in 42.5% of all surgically treated patients and were seen more commonly in patients with multiple surgical interventions (p = 0.005) and those operated on with the intent of en bloc resection (p = 0.006). CONCLUSIONS The extent of resection and metallic stabilization substantially influenced clinical outcomes for patients with spinal chordoma or chondrosarcoma despite high-dose adjuvant PBS-PT. Optimal upfront surgical management of these tumors continues to include GTR, as possible, with prompt adjuvant proton therapy.