Radiation-induced tumors (RITs) represent a rare yet serious long-term complication of ionizing radiation, particularly relevant in pediatric patients due to their long life expectancy. Proton therapy (PT) is widely used in children because of its favorable dose distribution compared to photon therapy. However, PT generates secondary neutrons that may contribute to RIT development. In a previously reported cohort of 119 children treated with pencil beam scanning (PBS) PT for intracranial ependymoma at the Paul Scherrer Institute (PSI), four RITs (3.4%) were observed after a median follow-up of 5.3 years. The present study aimed to explore potential risk factors for RITs within our institution's PBS-PT treatment protocol. A literature review identified one comparable cohort of 51 pediatric patients treated with commercial-like PBS-PT systems, in which no RITs were reported after a median follow-up of 5 years. In parallel, Monte Carlo simulations were performed to compare neutron production between the two PSI gantries. Neutron dose calculations revealed higher secondary neutron exposure associated with Gantry 1 compared to Gantry 2. Variability in system-specific neutron dose emissions may contribute to differential RIT risks. However, given the limited number of events, differences in follow-up duration, and potential confounding factors such as chemotherapy and treatment volumes, these findings should be considered hypothesis-generating. Continued optimization of PT delivery and long-term monitoring of pediatric patients treated with PBS-PT are required to establish causal relationship.

Background: RMS is the most common soft tissue sarcoma in children. Pencil beam scanning proton therapy (PBS PT) enables highly conformal dose delivery with reduced exposure to surrounding healthy structures, making it particularly suited for RMS in critical anatomical regions. Long-term clinical outcome data for this new radiation technique are scarce. Purpose: This study reports long-term outcomes and quality of life after PBS PT in children and adolescents with rhabdomyosarcoma (RMS). Methods and Materials: We retrospectively reviewed 114 children and adolescents with RMS (mostly embryonal, n = 100; 87.7%) treated between 2000 and 2020. Their median age was 4.6 years (range, 0.3–18). All received systemic chemotherapy according to prospective protocols. The median total PT dose delivered was 52 Gy (RBE; range, 41.4–64.8). Results: After a median follow-up period of 7.1 years (range, 0.3 to 17 years), we observed 26 failures overall; 21 (80.8%) occurred in-field. The 5-year local control and overall survival were 81.2% and 81%, respectively. The composite endpoint (non-ocular grade ≥3 toxicity- and failure-free survival) counting the first occurrence of any failure (local or distant), death, or non-ocular CTCAE v5.0 grade ≥3 toxicity was 77.3% at 5 years. At the start of PT, parents and children reported a quality of life significantly worse than that of a German normative group, but during the follow-up period, their scores improved to normal values in nearly all domains within two years. Conclusions: Our two decades of experience with PBS PT provide data that reflect good local control rates and minimal late non-ocular grade 3 toxicity. We also show that quality of life returned to normal scores in nearly all domains within 2 years. Children and adolescents with RMS seem to benefit from PBS PT in terms of toxicity and quality of life, but further prospective, multi-institutional comparative trials are needed.

Background and purpose:Standard care for head and neck cancer (HNC) treatment with proton therapy typically involves a 4-6 field Intensity Modulated Proton Therapy plan to enhance robustness towards anatomical changes and patient misalignments. This study aimed to evaluate whether a more efficient plan with fewer beams, designed for faster delivery, can be combined with online daily adaptation (DAPT) to provide treatment of comparable quality, and improve treatment outcomes. Materials and methods:We retrospectively analyzed five HNC patients with available daily 3D imaging treated at our institution. To simulate DAPT, synthetic Computed Tomography (CT) images were generated by deforming planning CT to each daily Cone-Beam CT with targets and organs-at-risk (OARs) propagated to daily images. Three plans were created per-patient: OfflineSBC and DAPTSBC with standard, and DAPTRBC with reduced, beam configuration. DAPTSBC and DAPTRBC were reoptimized on daily synCTs, while OfflineSBC followed clinical workflow, with offline replanning as needed. Results:OfflineSBC showed >5% target underdosage in 15% of fractions, with both adaptive approaches significantly improving coverage. Although DAPTRBC outperformed OfflineSBC for target coverage, its advantage in OARs sparing was less definitive. DAPTSBC reduced pooled average normal tissue dose across patients and fractions by 13% and pooled average normal tissue complication probability for xerostomia by 7%. Delivery of DAPTRBC with fewer beams was 24% faster than plans with conventional arrangement. Conclusions:Our delivery efficiency study shows that DAPT can allow fewer beams to achieve faster delivery, as shown in case of DAPTRBC workflow, and a reduction in the dose to normal tissue.

Background and purpose In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used to convert proton dose into an equivalent photon dose. However, RBE varies with tissue type, fraction dose, and beam quality parameters beyond dose such as linear energy transfer (LET) raising concerns about increased local effectiveness and potential toxicity. This work aims to harmonize quantities used for clinical consideration of variable RBE for proton therapy. Materials and methods A survey was distributed to proton centres to determine agreement on RBE-related concerns and clinical implementations. A subsequent clinical expert meeting facilitated by the European Particle Therapy Network was held to achieve consensus and to make clinical recommendations how to prescribe and report beyond using dose and constant RBE. Results The survey was answered by 17 out of 23 centres contacted (74%). For proton RBE, most concerns existed regarding toxicity in serial organs, while the assumption of an RBE of 1.1 was considered valid for targets. Most physicists intended to consider a physical quantity beyond dose in clinical decision making. Conclusions A constant RBE of 1.1 was the consensus for prescribing dose. However, current practice of recording and reporting dose in proton therapy must be complemented: the recommended quantity beyond dose was the dose-averaged LET in water from primary and secondary protons, normalized to unit density. This will facilitate analyses of treatment data on effectiveness beyond dose and between centres. No consensus on a single variable RBE model was found. More clinical training on proton RBE is needed.

BACKGROUND AND AIMS:To assess clinical outcomes and quality of life (QoL) of children, adolescents, and young adults (C-AYAs) with chordomas (CH) or chondrosarcomas (CS) after pencil beam scanning proton therapy (pbsPT). METHODS:A total of 76 C-AYAs treated between 1999 and 2023 were included. Median age was 16.6 years (1.5-25.4). A total of 44 (57.9%) were AYAs (15-25 years). Most tumors were CHs (n = 49; 64.5%) and located in the skull base (68.4%). Median radiation dose was 73.8 Gy (RBE) (54-75.6). A total of 26 (34.2%) patients underwent complete resection. PEDQOL questionnaire was used to assess QoL. Kaplan-Meier and log-rank tests were used for the analysis. RESULTS:With a median follow-up of 88.4 months (range, 1.8-257.6), 9 (11.8%) patients died. Local failure only developed in 9 (11.8%) patients. Two (2.6%) presented with distant failure only and another (1.3%) had both. Seven-years overall survival (OS), local control (LC), and distant control (DC) were 86.3%, 87.7%, and 95.7%, respectively. Children when compared to AYAs had worse 7-years DC (90% vs. 100%, p = 0.049). Surgical resection vs. biopsy was associated with better 7-years LC (87.1% vs. 67.7%, p = 0.031). Recurrent tumors showed worse OS, LC, and DC (94.5% vs. 44.6%, p < 0.001; 93.2% vs. 36.6%, p < 0.001; 98.3% vs. 77.6%, p = 0.003). Seven-years freedom from grade ≥3 late toxicity was 83.1%. Three (3.9%) children with CH developed secondary tumors. QoL did not differ from a healthy cohort 2 years after pbsPT. CONCLUSIONS:Excellent clinical outcomes with acceptable long-term toxicity and QoL were observed for C-AYAs with CH/CS after pbsPT. Recurrent tumors, young age, and lack of surgical resection were associated with worse prognosis.

Background and Purpose: Although reirradiation of glioblastoma has a long history of clinical practice, guidance on how to perform it in the context of recent technological advances, modern imaging modalities or systemic therapy is scarce. This joint ESTRO/EANO guideline aims to collect the existing evidence to produce recommendations for safe reirradiation of glioblastoma. Methods: The basis of this ESTRO/EANO clinical practice guideline are nine key questions (KQ) which were formulated by a consortium of radiation-oncologists, radiologists, medical oncologists, neurooncologists, medical physicists and radiation therapists. A systematic review was conducted and the KQ were addressed based on this evidence and expert opinion to draft recommendations and statements which were then voted on in a modified DELPHI process. Results: The DELPHI consensus process resulted in 18 recommendations and nine statements of which all achieved group consensus. Thirteen (48%) were based on available prospective evidence and 14 (52%) on expert opinion. Level of evidence did not exceed "moderate", reflecting the scarcity of prospective randomized evidence for most aspects of reirradiation. Consensus recommendations and statements reflected aspects of patient se- lection, imaging for recurrence assessment, target volume delineation, treatment planning, combined modality treatment, and follow-up. Conclusions: Currently, based on the ESTRO/EANO consensus, reirradiation may be considered in selected pa- tients with glioblastoma. GTV definition is based on T1-weighted MR-sequences, while a GTV to CTV margin is not mandatory. A PTV margin of maximum 3 mm is recommended based on the individual mask system and IGRT procedures. A biological effective dose greater than 36 Gy in 2 Gy fractions is recommended. A careful assessment of prognostic factors on survival such as age, interval from initial radiation, large treatment volumes, poor KPS, and poor neurologic/neurocognitive status is essential for making a clinical recommendation.