Early outcome after craniospinal irradiation with pencil beam scanning proton therapy for children, adolescents and young adults with brain tumors.

Central nervous system (CNS) tumors are the most common solid malignancies in children and adolescents and young adults (C-AYAs). Craniospinal irradiation (CSI) is an essential treatment component for some malignancies, but it can also lead to important toxicity. Pencil beam scanning proton therapy (PBSPT) allows for a minimization of dose delivered to organs at risk and, thus, potentially reduced acute and late toxicity. This study aims to report the clinical outcomes and toxicity rates after CSI for C-AYAs treated with PBSPT. Seventy-one C-AYAs (median age: 7.4 years) with CNS tumors were treated with CSI between 2004 and 2021. Medulloblastoma (n = 42: 59%) and ependymoma (n = 8; 11%) were the most common histologies. Median prescribed total PBSPT dose was 54 GyRBE (range: 18-60.4), and median prescribed craniospinal dose was 24 GyRBE (range: 18-36.8). Acute and late toxicities were coded according to Common Terminology Criteria for Adverse Events. After a median follow-up of 24.5 months, the estimated 2-year local control, distant control, and overall survival were 86.3%, 80.5%, and 84.7%, respectively. Late grade ≥3 toxicity-free rate was 92.6% at 2 years. Recurrent and metastatic tumors were associated with worse outcome. In conclusion, excellent tumor control with low toxicity rates was observed in C-AYAs with brain tumors treated with CSI using PBSPT.

Achieving a Pathologic Complete Response for Locally Advanced Esophageal Adenocarcinoma Using Cone-Beam Computed Tomography-Based Online Adaptive Radiotherapy.

Neo-adjuvant chemoradiotherapy (CRT) and perioperative chemotherapy are different strategies for treating non-metastatic esophageal cancer (EC). The advantages of neo-adjuvant therapies are primarily seen in patients who achieve a pathologic complete response (pCR) and therefore show higher survival rates and better prognosis. In general, less than one-third of patients with EC experience pCR after neo-adjuvant therapies; however, patients with esophageal adenocarcinoma (AC) demonstrate lower rates of pCR compared to those with esophageal squamous cell carcinoma (SCC), respectively. Herein, we describe two cases of locally advanced esophageal AC treated with cone-beam computed tomography (CBCT)-based online adaptive radiotherapy (ART) on the ETHOS platform. Both patients received CRT with 50.4 Gy in 28 fractions, combined with weekly carboplatin and paclitaxel. For each fraction, we evaluated scheduled and adapted plans using dose-volume histogram (DVH) data, and patients were treated with the superior plan. We prioritized ensuring optimal coverage of the planning target volume (PTV) over limiting the dose to organs at risk (OARs) when selecting the superior treatment plan. In this instance, we present the translation of superior dosimetric data into clinical benefits, as evidenced by an excellent pathologic response.

Craniospinal irradiation using pencil beam Scanning: The PSI experience.

INTRODUCTION: We present the dosimetric evaluation of craniospinal irradiation (CSI) treatments delivered with protons at Paul Scherrer Institute (PSI), with special focus on local recurrences and late toxicity outcome. METHODS: This study included 71 children, adolescents and young adults (c-AYA), who received or intended to receive (3 patients, pts) CSI using PBS-PT at PSI between 2004 and January 2021. The most frequent primary tumours were: medulloblastoma (42 pts), ependymoma (8 pts) and germ cell tumors (6 pts). The patients were treated prone on Gantry1 (G1; 22 pts) up to 2017, and afterwards supine on Gantry2 (G2; 49 pts). Accuracy of prone vs. supine setup was evaluated. Nine patients received CSI for local failure (LF) after a first course of local fractionated radiation therapy (RT). For 59/71 patients (excluding three patients not receiving PBS-PT CSI and nine preirradiated) CSI plans were compared considering gantry and planning technique. Detailed analysis of the full treatment (CSI and boost series) was performed for 8 patients presenting with LFs (4 of them presented also distal failure) and for selected patients presenting with late toxicity (G2 to G4) or asymptomatic radiation-induced radiological findings. RESULTS: Supine positioning resulted in lower systematic and random errors as compared to prone (0.25 mm and 0.4 mm systematic errors respectively for supine and prone; random errors in PA direction reduced from 1.8 mm for prone to 1.4 mm for supine). CONCLUSIONS: LFs were not correlated with potential dose inaccuracies or lack of robustness and no correlation of toxicities to enhanced LET have been observed.

Clinical outcome after pencil beam scanning proton therapy and dysphagia/xerostomia NTCP calculations of proton and photon radiotherapy delivered to patients with cancer of the major salivary glands.

OBJECTIVES: The purpose of this study is to report the oncological outcome, observed toxicities and normal tissue complication probability (NTCP) calculation for pencil beam scanning (PBS) PT delivered to salivary gland tumour (SGT) patients. METHODS: We retrospectively reviewed 26 SGT patients treated with PBSPT (median dose, 67.5 Gy(RBE)) between 2005 and 2020 at our institute. Toxicities were recorded according to CTCAEv.4.1. Overall survival (OS), local control (LC), locoregional control (LRC) and distant control (DC) were estimated. For all patients, a photon plan was re-calculated in order to assess the photon/proton NTCP. RESULTS: With a median follow-up time of 46 months (range, 3-118), 5 (19%), 2 (8%), 3 (12%) and 2 (8%) patients presented after PT with distant, local, locoregional failures and death, respectively. The estimated 4 year OS, LC, LCR and DC were 90%, 90%, 87 and 77%, respectively. Grade 3 late toxicity was observed in 2 (8%) patients. The estimated 4 year late high-grade (≥3) toxicity-free survival was 78.4%. The calculated mean difference of NTCP-values after PBSPT and VMAT plans for developing Grade 2 or 3 xerostomia were 3.8 and 2.9%, respectively. For Grade 2-3 dysphagia, the grade corresponding percentages were 8.6 and 1.9%. Not using an up-front model-based approach to select patients for PT, only 40% of our patients met the Dutch eligibility criteria. CONCLUSION: Our data suggest excellent oncological outcome and low late toxicity rates for patients with SGT treated with PBSPT. NTCP calculation showed a substantial risk reduction for Grade 2 or 3 xerostomia and dysphagia in some SGT patients, while for others, no clear benefit was seen with protons, suggesting that comparative planning should be performed routinely for these patients. ADVANCES IN KNOWLEDGE: We have reported that the clinical outcome of SGT patients treated with PT and compared IMPT to VMAT for the treatment of salivary gland tumour and have observed that protons delivered significantly less dose to organs at risks and were associated with less NTCP for xerostomia and dysphagia. Noteworthy, not using an up-front model-based approach, only 40% of our patients met the Dutch eligibility criteria.

Clinical Outcome After Pencil Beam Scanning Proton Therapy of Patients With Non-Metastatic Malignant and Benign Peripheral Nerve Sheath Tumors.

Objective: Peripheral nerve sheath tumors (PNSTs) commonly arise from peripheral nerve roots and grow locally invasive. Malignant PNSTs (mPNSTs) represent aggressive sarcomas of neural origin that can originate from PNSTs. Radiation therapy is commonly used as part of the required multimodal treatment. However, both entities tend to occur early in life and are associated with the genetic disorder neurofibromatosis type 1 (NF-1), which is known to cause increased radiosensitivity. Pencil beam scanning proton therapy (PBSPT) allows for a minimization of the dose delivered to organs at risk and the integral dose and, thus, potentially also a reduction of radiation-induced adverse events. We report the clinical outcome and toxicity rates of patients with (m)PNSTs treated with PBSPT. Methods: We retrospectively reviewed 36 patients who received PBSPT (median dose, 64 GyRBE) with curative intent for (m)PNSTs between 1999 and 2020 at our institute. Twenty-eight (78%) and 8 (22%) patients were treated at diagnosis and for tumor recurrence/progression, respectively. The median age was 32 years (range, 3-75), and 25 (69%) patients were male. mPNST and PNST were diagnosed in 31 (86%) and 5 (14%) patients, respectively. Underlying NF-1 disease was found in 8 (22%) patients. Acute and late toxicities were recorded according to Common Terminology Criteria for Adverse Events, version 4.1 (CTCAE v4.1). Overall survival (OS), local control (LC), and distant control (DC) were estimated using the Kaplan-Meier method. Results: With a median follow-up time of 31 months (range, 4-194), 13 (36%) patients died from a progressive disease, 8 (22%) experienced local failure, and 14 (39%) experienced distant failure after PBSPT. Estimated 2-year OS, LC, and DC were 75.5%, 73.5%, and 61.2%, respectively. Acute grade 3 toxicity (dermatitis, mucositis, and pain) was observed in 5 (14%) patients. Late grade 3 cataract and osteonecrosis were both observed in 1 (3%) patient at 34 and 194 months after PBSPT, respectively. There was no late grade >3 toxicity or radiation-induced secondary cancer. Conclusion: To our knowledge, this is the first study to analyze the outcome of (m)PNSTs treated with proton therapy using a PBS delivery paradigm. In our cohort, consisting mainly of patients with mPNSTs, we report reasonable oncological outcomes and low toxicity rates after PBSPT.