Pencil Beam Scanning Proton Therapy for Adolescents and Young Adults with Head and Neck Sarcomas.

Purpose: To assess clinical outcomes of adolescents and young adults (AYAs) with head and neck sarcomas (HNSs) treated with pencil beam scanning proton therapy (PBSPT) and to report quality of life (QoL). Materials and Methods: Twenty-eight AYAs (aged 15 to 39 years) with HNS treated between January 2001 and July 2022 at our institution were included. The median age was 21.6 years. Rhabdomyosarcoma (39.3%), Ewing sarcoma (17.9%), chondrosarcoma (14.3%), and osteosarcoma (14.3%) were the most frequent diagnoses. Three (10.7%) patients were metastatic before PBSPT and 13 (46.4%) patients had a tumor with intracranial extension. The median total radiation dose was 63 GyRBE (range, 45 to 74 GyRBE). Thirteen (46.4%) patients received concomitant chemotherapy. Toxicity was reported according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US National Institutes of Health, Bethesda, Maryland). Survival was estimated using the Kaplan-Meier method. QoL was assessed using a PEDQOL (Pediatric Quality of Life Questionnaire) questionnaire. Self-reported outcomes were assessed using institutional questionnaires. Results: With a median follow-up of 57 months (range, 3.7 to 243 months), 5 patients (17.8%) had local failure (LF) only, 2 (7.1%) experienced distant failure (DF) only, and 2 (7.1%) had LF and DF. The estimated 5-year local control (LC) and distant control (DC) rates were 71.8% and 80.5%, respectively. The median times to LF and DF were 13.4 and 22.2 months, respectively. Four (14.3%) patients died, all but one from their HNS. Estimated 5-year overall survival was 90.7%. Six (21.4%) patients developed nonocular grade ≥3 toxicity, which consisted of otitis media (n = 2), hearing impairment (n = 2), osteoradionecrosis (n = 1), and sinusitis (n = 1). Four (14.3%) patients developed cataracts that required surgery. The 5-year freedom from nonocular grade 3 toxicity was 91.1%. No grade 4 or higher toxicity was observed. Adolescents rated their quality of life before treatment worse than their parents did. Conclusion: Excellent outcomes with acceptable late-toxicity rates were observed for AYAs with HNS after PBSPT.

Quality of Life, Clinical, and Patient-Reported Outcomes after Pencil Beam Scanning Proton Therapy Delivered for Intracranial Grade WHO 1-2 Meningioma in Children and Adolescents.

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.

Quality-of-life evaluations in children and adolescents with Ewing sarcoma treated with pencil-beam-scanning proton therapy.

BACKGROUND: With improved survival rates for children with cancer, quality-of-life (QoL) issues have increasingly become the focus of attention. We report the QoL of children with Ewing sarcoma (EWS) treated with pencil-beam-scanning proton therapy (PT). METHODS: A PEDQOL (QoL questionnaire for children 4-18 years) self/proxy questionnaire was used to prospectively assess the QoL of 23 children <18 years with EWS treated with PT. This questionnaire evaluates eight different domains. Children (self-rating) and parents (proxy-rating) filled out the questionnaire at the start of PT (E1), 2 months after treatment (E2), and thereafter once yearly (E≥3). RESULTS: Compared with healthy controls, parents rated the QoL of their children at E1 significantly worse in all but two (cognition and social functioning-family) domains. At E4, significant differences between the two groups only remained in three of eight domains. At E1, children self-rated their QoL significantly worse in the domain Physical functioning (p = .004) and significantly better in the domain Body image (p = .044) compared to healthy controls, whereas no significant differences were observed at E4. For the longitudinal comparison E1 versus E4, according to parents, Emotional functioning, Cognition and Social functioning-peers were slightly decreased 2 years after PT. The children rated Emotional functioning and Body image poorly 2 years after PT. CONCLUSIONS: Children with EWS usually recovered seemingly well to normal QoL levels 2 years after the end of PT. They tended to rate their QoL substantially higher than their parents. However, in the longitudinal analysis at 2 years, children rated their Emotional functioning and Body image scores poorly.

A Prospective Study on Health-Related Quality of Life and Patient-Reported Outcomes in Adult Brain Tumor Patients Treated with Pencil Beam Scanning Proton Therapy.

Proton therapy (PT) is delivered to complex brain tumors to obtain an optimal curative treatment with limited toxicity. Value-based oncological medicine is increasingly important, particularly when long-term survival is to be expected. This study aims to evaluate health-related quality of life (HRQOL) and patient reported outcomes (PROs) in patients treated with PT for brain tumors. Adult patients with brain tumors treated with PT filled out the EORTC-QLQ-C30 and BN20 questionnaires up to three years following PT. Toxicity was scored using the CTCAE v4.03. QoL and PRO were correlated to clinical factors. Three-year overall survival, distant brain control and local control rates were 98%, 97% and 84%, respectively. No ≥G3 acute toxicity was observed. Late PT-related ≥G3 severe toxicity occurred in seven patients (5.7%). Lower global QoL scores after PT were significantly correlated to low Karnofsky performance status (KPS) before PT (p = 0.001), surgical complications before PT (p = 0.04) and progressive disease (p = 0.017). A low QLQ-30 summary score at one year follow-up was correlated to sex (p = 0.015), low KPS before PT (p < 0.001), and central nervous system symptoms before PT (p = 0.018). Reported QLQ-BN20 neurological symptoms were correlated to lower KPS at baseline (p < 0.001) and surgical complications before PT (p = 0.03). PT-related toxicity only influenced reported symptoms directly following PT, but not QoL. Although global QoL temporarily decreased after treatment, it improved again from one year onwards. Global QoL and reported symptoms over time were not correlated with the proton therapy and were more related to preexisting symptoms and progressive disease. This study assists in improving patient support in patients with brain tumors receiving PT.

Clinical outcomes of head and neck adenoid cystic carcinoma patients treated with pencil beam-scanning proton therapy.

OBJECTIVE: The aim of this study was to evaluate the outcome of patients with head and neck adenoid cystic carcinoma (ACC) treated using pencil beam scanning proton therapy (PBS PT) at our institution. MATERIALS AND METHODS: Thirty-five patients who underwent treatment with PBS PT for ACC between 2001 and 2017 were included. Local control (LC), distant control (DC), progression-free survival (PFS), overall survival (OS) and their prognostic factors were evaluated. Adverse effects were prospectively assessed. RESULTS: The median patient follow-up was 30 months. Prior to PT, 26 patients (74.3%) underwent surgery with R0/R1/R2 outcome in 5, 13 and 8 cases, respectively. Nine patients (25.7%) presented with inoperable disease. The 2-year LC, DC, PFS and OS was 92.2%, 77.8%, 74.3% and 88.8%, respectively. LC was influenced by patient age (p = 0.002) with a significant difference between local and distant failure (median 61.3 vs. 42.3 years, p = 0.005). Tumor T stage was a significant risk factor for PFS (p = 0.045) and tumor prognostic group affected OS (p = 0.049). No significant survival advantage for operable vs. inoperable disease could be identified. The acute and late grade 3 toxicity rates were 14.3% and 6.1%, respectively. No acute or late grade 4/5 toxicities were observed. CONCLUSIONS: PBS PT is an effective and safe treatment for patients with head & neck ACC in both definitive and adjuvant setting. Distant metastases are the main pattern of failure. Age, tumor stage and clinical stage had a significant negative impact on LC, OS and PFS.