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

Tumor control and QoL outcomes of very young children with atypical teratoid/rhabdoid tumor treated with focal only chemo-radiation therapy using pencil beam scanning proton therapy

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 ± 7.0 months. 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 54 Gy (RBE). After a median follow-up of 33.4 months (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 >2 years. Acute toxicity was manageable. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and treatment-induced toxicity

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

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

Proton therapy for brain tumours in the area of evidence-based medicine.

ADVANCES IN KNOWLEDGE This review details the indication of brain tumors for proton therapy and give a list of the open prospective trials for these challenging tumors

Long-Term Clinical Safety of High-Dose Proton Radiation Therapy Delivered With Pencil Beam Scanning Technique for Extracranial Chordomas and Chondrosarcomas in Adult Patients: Clinical Evidence of Spinal Cord Tolerance.

PURPOSE To assess the radiation dose tolerance of the spinal cord by reviewing our institutional experience regarding the incidence of radiation-induced spinal cord toxicity after high-dose pencil beam scanning proton therapy (PBSPT). METHODS AND MATERIALS Seventy-six patients (median age 53 years; range, 23-79 years) treated for spinal chordoma (n=55) or chondrosarcoma (n=21) met the following criteria and were retrospectively analyzed: PBSPT only, no reirradiation or concomitant chemotherapy, maximum dose (Dmax) to the spinal cord of ≥45 Gy(relative biological effectiveness [RBE]), ≥18 years of age, and follow-up of ≥12 months. The delivered dose was 59.4 to 75.2 Gy(RBE) [median 73.9 Gy(RBE)] delivered with conventional fractionation between 2000 and 2014. The Dmax, D2%, and V40-V60 of the surface (sSC) and center (cSC) of the spinal cord were recorded. Toxicity was scored according to the Common Terminology Criteria for Adverse Events, version 4.03. RESULTS Median follow-up was 65.5 months (range, 13-173 months). Patients received a mean Dmax and D2% to the sSC of 59.0 (median 58.7; range, 48.3-75.9) and 55.3 (median 52.7; range, 43.1-73.8) Gy(RBE), respectively. The corresponding values for the cSC were 52.3 (median 52.7; range, 32.3-73.3) and 51.1 (median 52.0; range, 25.3-73.1) Gy(RBE), respectively. Four patients (5%) developed acute radiation-induced neurotoxicity (grade [G] 1, n=1; G2, n=3). Twelve patients (16%) experienced late neurologic toxicities (G1, n=7; G2, n=4; G4, n=1). One patient with a history of pre-PBSPT symptomatic spinal cord compression redeveloped tetraplegia (G4) after receiving a Dmax of 57.8 Gy(RBE) to the sSC and 54.1 Gy(RBE) to the cSC. No significant correlation was found between sSC Dmax and D2%, cSC Dmax and D2%, or the length of CTV and toxicity. CONCLUSIONS High-dose conformal PBSPT may be delivered safely in close proximity to the spinal cord with minimal neurotoxicity. Dose constraints of 64 Gy(RBE) as D2% for the sSC and 54 Gy(RBE) for the cSC seem appropriate for clinical use

Long term outcomes of patients with skull-base low-grade chondrosarcoma and chordoma patients treated with pencil beam scanning proton therapy

To evaluate the long term tumor control and toxicity of skull base tumors treated with pencil beam scanning proton therapy (PT)

Long-Term Clinical Outcomes of Pencil Beam Scanning Proton Therapy for Benign and Non-benign Intracranial Meningiomas.

PURPOSE To assess and report long-term clinical outcomes regarding local control, overall survival, and toxicity-free survival after pencil beam scanning proton therapy for intracranial meningiomas at a single institution. PATIENTS AND METHODS Ninety-six patients (male/female, 29/67; median age 52.8 years) with intracranial meningiomas (World Health Organization [WHO] grade 1, n=61 [63.5%]; WHO grade 2, n=33 [34.4%]; WHO grade 3, n=2 [2.1%]) were treated with pencil beam scanning proton therapy (n=53 [55.2%] at diagnosis, n=17 [17.7%] at recurrence, and n=26 [27.1%] for tumor progression). Median gross tumor volume before PBSPT was 21.4 cm3 (range, 0.0-546.5 cm3), with a median planning target volume of 123.4 cm3 (range, 4.6-1142.0 cm3). Median duration of follow-up was 56.9 months (range, 12.1-207.2 months). Late toxicity was graded according to the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS Thirteen failures (14%) (male/female, 6/7) were observed, of which the majority (n=9, 69%) were of non-benign histology. The 5-year actuarial local control and overall survival were 86.4% and 88.2%, respectively. Five-year grade ≥3 toxicity-free survival was 89.1%. On univariate analysis, local control was worse for patients with higher WHO grade (P≤.001), those treated after at least 1 recurrence (P=.006), those with non-skull base tumor location (P=.014), and males (P=.032). Significant prognosticators for 5-year overall survival were local control (P≤.001), age (P=.002), and timing of proton therapy (initial vs recurrence) (P=.002). CONCLUSIONS Pencil beam scanning proton therapy is an effective and safe treatment for patients with intracranial meningiomas, resulting in high local control rates with limited toxicity. Up-front radiation likely results in improved outcomes and should be considered, especially for patients with non-benign tumors and/or for those with incomplete resections

Tumor control and QoL outcomes of very young children with atypical teratoid/rhabdoid Tumor treated with focal only chemo-radiation therapy using pencil beam scanning proton therapy

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