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Abstract Background Due to the increasing expertise in transoral laser surgery and image-guided radiation therapy, treatment outcomes have recently improved in patients with early-stage glottic cancer. The objective of the current study was to evaluate intensity-modulated proton therapy (IMPT) as novel treatment option. Methods A total of 15 patients with T1-2N0 glottic squamous cell carcinoma, treated between 2017 and 2020, were evaluated. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Results The majority were T1a/b tumors (66.7%) and no patient had lymph node or distant metastases. The median total dose was 70 Gy relative biological effectiveness (RBE) (range 66–70 Gy RBE). The one- and two-year OS and metastases-free survival were 100%. One patient developed local failure and received salvage laryngectomy. No higher-grade acute or late toxicity was reported. The mean number of CTCAE grade I and II overall toxicity events per patient was 4.1 (95%-[confidence interval] CI 3.1–5.3) and 1.0 (95%-CI 0.5–1.5). Conclusion High-precision proton therapy of T1-2N0 glottic cancer resulted in exceptional treatment tolerability with high rates of laryngeal function preservation and promising oncological outcome. IMPT has the potential to become a standard treatment option for patients with early-stage laryngeal cancer.

Abstract Background Carbon ion radiotherapy (CIRT) yields biophysical advantages compared to photons but randomized studies for the reirradiation setting are pending. The aim of the current project was to evaluate potential clinical benefits and drawbacks of CIRT compared to volumetric modulated arc therapy (VMAT) in recurrent head and neck cancer. Methods Dose-volume parameters and local failure patterns of CIRT compared to VMAT were evaluate in 16 patients from the randomized CARE trial on head and neck cancer reirradiation. Results Despite an increased target dose, CIRT resulted in significantly reduced organ at risk (OAR) dose across all patients (− 8.7% Dmean). The dose-volume benefits were most pronounced in the brainstem (− 20.7% Dmax) and the optic chiasma (− 13.0% Dmax). The most frequent local failure was type E (extraneous; 50%), followed type B (peripheral; 33%) and type A (central; 17%). In one patient with type A biological and/or dosimetric failure after CIRT, mMKM dose recalculation revealed reduced target coverage. Conclusions CIRT resulted in highly improved critical OAR sparing compared to VMAT across all head and neck cancer reirradiation scenarios despite an increased prescription dose. Local failure pattern analysis revealed further potential CIRT specific clinical benefits and potential pitfalls with regard to image-guidance and biological dose-optimization.

Abstract Background Intensity-modulated re-radiotherapy (reIMRT) has been established as a standard local treatment option in patients with non-resectable, recurrent head and neck cancer (rHNC). However, the clinical outcome is unfavorable and severe toxicities (≥grade III) occurred in 30–40% of patients. The primary aim of the current trial is to investigate carbon ion reirradiation (reCIRT) compared to reIMRT in patients with rHNC regarding safety/toxicity as well as local control, overall survival (OS), and quality of life (QoL). Methods The present trial will be performed as a single center, two-armed, prospective phase II study. A maximum of 72 patients will be treated with either reIMRT or reCIRT to evaluate severe (≥grade III) treatment-related toxicities (randomization ratio 1:1). The primary target value is to generate less than 35% acute/subacute severe toxicity (≥grade III), according to the Common Terminology Criteria for Adverse Events v5.0, within 6 months after study treatment. The total dose of reirradiation will range between 51 and 60 Gy or Gy (RBE), depending primarily on the radiotherapy interval and the cumulative dose to organs at risk. Individual dose prescription will be at the discretion of the treating radiation oncologist. The local and distant progression-free survival 12 months after reirradiation, the OS, and the QoL are the secondary endpoints of the trial. Explorative trial objectives are the longitudinal investigation of clinical patient-related parameters, tumor parameters on radiological imaging, and blood-based tumor analytics. Discussion Recent retrospective studies suggested that reCIRT could represent a feasible and effective treatment modality for rHNC. This current randomized prospective trial is the first to investigate the toxicity and clinical outcome of reCIRT compared to reIMRT in patients with rHNC. Trial registration ClinicalTrials.gov ; NCT04185974 ; December 4th 2019.

Advanced radiation techniques can reduce the severity of neurocognitive sequelae in young brain tumor patients. In the present analysis, we sought to compare neurocognitive outcomes after proton irradiation with patients who underwent photon radiotherapy (RT) and surgery. Neurocognitive outcomes were evaluated in 103 pediatric brain tumor patients (proton RT n = 26, photon RT n = 30, surgery n = 47) before and after treatment. Comparison of neurocognitive outcomes following different treatment modalities were analyzed over four years after treatment completion. Longitudinal analyses included 42 months of follow-up after proton RT and 55 months after photon RT and surgery. Neurocognitive assessment included standardized tests examining seven domains. A comparison of neurocognitive outcomes after RT (proton and photon with >90% additional surgery) and surgery showed no significant differences in any neurocognitive domain. Neurocognitive functioning tests after proton RT failed to identify alterations compared to baseline testing. Long-term follow up over four years after photon RT showed a decrease in non-verbal intelligence (−9.6%; p = 0.01) and visuospatial construction (−14.9%; p = 0.02). After surgery, there was a decline in non-verbal intelligence (−10.7%; p = 0.01) and processing speed (14.9%; p = 0.002). Differences in neurocognitive outcomes between RT and surgical cohorts in direct intermodal comparison at long-term follow-up were not identified in our study, suggesting that modern radiation therapy does not affect cognition as much as in the past. There were no alterations in long-term neurocognitive abilities after proton RT, whereas decline of processing speed, non-verbal intelligence, and visuospatial abilities were observed after both photon RT and surgery. Domains dependent on intact white matter structures appear particularly vulnerable to brain tumor treatment irrespective of treatment approach.