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Proton beam radiotherapy (PRT) is used in the treatment of low-grade glioma (LGG) to mitigate long-term sequelae. Following PRT, increased rates of radiation-induced contrast enhancements (RICE) are suspected but poorly understood. We analyzed consecutive 227 patients (42 children and 185 adults) treated with PRT (54Gy RBE) for LGG from 2010 to 2020 and followed with serial clinical exams and magnetic resonance imaging for in median 5.6 years. Tumors were graded WHO 1 in a minority (n = 22, 12%) of adults, but a majority of children (n = 29, 69%). In contrast, tumors were graded WHO 2 in the majority (n = 160, 87%) of adults and a minority of children (n = 10, 24%). Five-year overall survival following PRT was 81% in adults and 91% in children. The risk of RICE was 5-fold more frequent in adults (25%) versus children (5%) (p = 0.0043). Also, within the adult cohort, RICE risk increases with age (p = 0,00128). In children and adults, RICE were symptomatic in 50% and 55% (n = 1 and 26) of cases with CTCAE grade 0 in 47% (n = 23), grade 1 in 25% (n = 12), 0% grade 2 (n = 0) and 29% grade 3 (n = 14), respectively. In adults, RICE risk was associated to WHO grading (8% in WHO grade 1 vs. 24% in WHO grade 2, p = 0.026), independent of age (p = 0.44) and irradiation dose (p = 0.005), but not independent of IDH mutational status. These data demonstrate effectiveness of PRT for LGG in both children and adults. The RICE risk is lower in children which are a main target group for PRT and differs with WHO grading.

Meningiomas represent the most common primary brain tumor type, with a recurrence rate of approximately 20% following resection. Classification by molecular classes was demonstrated to be more accurate in identifying patients at high risk of disease progression in meningiomas, compared to WHO grading only. Novel radiotherapeutic modalities using protons or carbon ions provide an increased relative biological effectiveness (RBE) compared to photons, enabling a higher local dose deposition while reducing the radiation dose for organs of risks. The prospective single-arm phase II - MARCIE trial investigated a bimodal radiotherapy using photons (50 Gy in 25 fractions) and a carbon-ions boost with 18 Gy (RBE) in 6 fractions. Local progression-free survival after 3 years was defined as primary endpoint. In total, 33 patients were recruited before termination of the trial. After 3 years, local progression free survival was estimated at 94.7% and overall survival at 89.8%. Serious adverse events in the form of radiation necrosis were observed in 3 cases, requiring a subsequent treatment with bevacizumab. Post-hoc DNA methylation profiling revealed that relapses occur more frequently in high-risk meningiomas following radiotherapy, compared to the intermediate risk-group, confirming the prognostic relevance of the methylation-based meningioma classifier.Subsequently, a retrospective matched-pair analysis was performed to compare irradiated (n > 100) and non-irradiated meningiomas, stratified into the molecular risk groups (ben, int, high). The clinical benefit of postoperative radiotherapy and dose escalation with regard to the local control are currently being assessed for the respective molecular meningioma classes. Postoperative, bimodal radiotherapy with carbon-ion boost represent an auspicious treatment modality with an excellent local tumor control following resection. Molecular risk stratification is crucial in identifying patients who might benefit from postoperative radiotherapy.

We aimed to evaluate the treatment outcome of primary and postoperative bimodal radiotherapy (RT) including intensity modulated photon radiotherapy (IMRT) and carbon ion radiotherapy (CIRT) for sinonasal adenoid cystic carcinoma (ACC) patients. Medical records of 227 consecutive patients who received either a primary (n = 90, 40%) or postoperative (n = 137, 60%, R2, n = 86, 63%) IMRT with doses between 48 and 56 Gy in 1.8 or 2 Gy fractions and active raster-scanning carbon ion boost with 18 to 24 Gy (RBE, relative biological effectiveness) in 3 Gy (RBE) fractions between 2009 and 2019 up to a median total dose of 80 Gy (EQD2, equivalent dose in 2 Gy single dose fractions, range 71&ndash, 80 Gy) were reviewed. Results: Median follow-up was 50 months. In univariate and multivariate analysis, no significant difference in local control (LC) could be shown between the two treatment groups (p = 0.33). Corresponding 3-year LC rates were 79% for primary bimodal RT and 82% for postoperative bimodal RT, respectively. T4 stage (p = 0.002) and solid histology (p = 0.005) were identified as independent prognostic factors for decreased LC. Significant worse long-term treatment tolerance was observed for postoperatively irradiated patients with 17% vs. 6% late grade 3 toxicity (p &lt, 0.001). Primary radiotherapy including IMRT and carbon ion boost for dose-escalation results in adequate LC with less long-term grade 3 toxicity compared to postoperative bimodal radiotherapy in sinonasal ACC patients. The high rate of macroscopic tumor disease in the postoperative group makes the interpretation of the beneficial results in LC for primary RT difficult.

Renal cell carcinoma (RCC) is traditionally considered to be radioresistant. Radiotherapy response rates are believed to improve with hypofractionated, high dose stereotactic body radiotherapy (SBRT). However, limited data exist regarding the role of SBRT in the treatment of pulmonary metastases.The working group "Stereotactic Radiotherapy" of the German Society of Radiation Oncology analyzed its multi-institutional database of more than 700 patients who received SBRT for pulmonary metastases. Treatment was performed at 10 centers between 2001 and 2016. Patients with metastatic RCC were included in the study. Tumor characteristics, treatment details, and follow-up data including survival, local control (LC), distant metastases, and toxicity were evaluated.A total of 46 RCC patients treated with SBRT for 67 lung metastases were identified, who received a median total biologically effective dose (BEDSBRT for pulmonary metastases from RCC was associated with low treatment-associated toxicity, promising survival, and excellent LC, especially in those patients receiving a BED

Purpose: Salvage surgery of recurrent hypopharyngeal and laryngeal squamous cell carcinoma (SCC) results in limited local control and survival rates. As a result of recent technological progress, radiotherapy (RT) has become a valuable, potentially curative therapeutic option. Thus, we aimed to determine prognostic factors for survival outcome in order to optimize patient selection for salvage radiotherapy after failure of first-line treatment with surgery alone in this special patient cohort. Methods: Seventy-five patients (85% male, median age of 64 years) underwent salvage RT in a secondary setting for recurrent hypopharyngeal or laryngeal SCC after prior surgery alone between 2007 and 2017. On average, patients were treated with one prior surgery (range 1–4 surgeries). Median time between surgery and salvage RT was 7 months (range 1–47 months) for initially advanced tumors (T3/4, N+, extracapsular spread) and 18 months (range 5–333 months) for initially early stage tumors. The majority of patients received concomitant chemotherapy (n = 48; 64%) or other kind of systemic treatment concurrent to radiotherapy (n = 10; 13%). Results: Median follow-up was 41 months (range 3–120 months). Overall, fifteen patients were diagnosed with local failure (all were in-field) at last follow-up (20%). Median time to recurrence was 35 months (range 3–120 months) and 3-year local progression-free survival (LPFS) was 75%, respectively. Dose-escalated RT with 70.4 Gy applied in 2.1 Gy or 2.2 Gy fractions corresponding an EQD2 > 70 Gy (p = 0.032) and the use of concomitant cisplatin weekly chemotherapy (p = 0.006) had a significant positive impact on LPFS. 3-year OS and DPFS were 76 and 85%, respectively. No toxicity-related deaths occurred. Reported grade > 3 side effects were rare (n = 4/70, 6%). Conclusion: Salvage radiotherapy resulted in excellent local control rates while radiation dose and the use of cisplatin weekly chemotherapy were identified as prognostic factors for LPFS. Nevertheless, patient selection for curative salvage treatment remains challenging.

Radiotherapy and oncology 127(Supplement 1), PV-0043 (2018). doi:10.1016/S0167-8140(18)30353-0 special issue: "ESTRO 37, April 20-24, 2018, Barcelona, Spain", Published by Elsevier Science, Amsterdam [u.a.]