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Due to their rarity, histologic heterogeneity, and localization, treatment of malignant salivary gland tumors requires an interdisciplinary approach. First-line treatment includes complete tumor resection. Postoperative radiation therapy is advised in patients with risk factors, i.e., incomplete tumor resection, high-grade tumors, or perineural invasion. Definitive radiation therapy is only advised for inoperable tumors because of significantly lower local control and survival rates when compared to combined surgery and radiation therapy. In radiation oncology, modern techniques such as intensity-modulated radiation therapy (IMRT) or particle therapy with heavy ions (i.e., C12) have led to improved outcomes in the treatment of head and neck tumors, especially of adenoid cystic carcinomas. Given the biological and physical benefits of particles, particle therapy, particularly carbon ion radiation, is a promising therapeutic approach for salivary gland tumors that will be further investigated in prospective clinical studies.Die Therapie der malignen Speicheldrüsentumoren ist aufgrund der heterogenen Histologie und Lokalisation eine interdisziplinäre Aufgabe. Primär wird die vollständige Resektion des Tumors empfohlen. Eine Radiotherapie (RT) ist postoperativ indiziert bei inkompletter Resektion oder Vorliegen von Risikofaktoren, die für eine aggressive Ausbreitung des Tumors sprechen (u. a. High-Grade-Tumoren, Perineuralscheideninfiltration). Eine definitive RT ist bei inoperablen Tumoren möglich, sollte jedoch bei Möglichkeit einer R0-Resektion hintenangestellt werden. In den letzten Jahren konnte auf dem Gebiet der Radioonkologie durch die Weiterentwicklung moderner Therapieverfahren und den Einsatz der Partikel-RT insbesondere beim adenoidzystischen Karzinom (ACC) bereits eine höhere lokale Kontrollrate oder eine Reduktion der Nebenwirkungen im Vergleich zur konventionellen Photonen-RT beobachtet werden. Aufgrund der biologischen und physikalischen Vorteile sowie erster klinischer Studien ist die Partikel-RT, v. a. mit Kohlenstoffionen, ein vielversprechendes Konzept für die Therapie der Speicheldrüsenkarzinome. Ergebnisse weiterer prospektiver Studien werden erwartet, um den Stellenwert der Partikel-RT in der Therapie der Speicheldrüsentumoren zu stärken.

Simple Summary Since inception, radiation therapy in pediatric brain tumor patients has been associated with neurocognitive decline and persistent impairment. Recently published studies suggest improved cognitive outcomes with advanced radiation techniques due to increased conformality. Our study compares different treatment modalities through longitudinal assessment of seven neurocognitive domains as well as examining the overall effect on scholastic performance in long-term follow-up more than four years after treatment. Comprehensive data were available due to interdisciplinary cooperation of pediatric neuro-oncologists, radiation oncologists, neurosurgeons, and clinical psychologists. To our knowledge, only a few such detailed testing results have been published, allowing a more granular examination of neurocognitive outcomes rather than basic IQ testing. Our study was able to show no differences in performance after adding modern conformal proton or photon radiation therapy to surgery compared to surgery alone. We could rule out radiation therapy as severe confounding factor in neurocognitive decline after brain tumor treatment in our study. Abstract 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.

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.

Background Delivery of stereotactic body radiotherapy (SBRT) to ultracentral lung tumors remains a major challenge, with potentially excessive SBRT-related toxicity. This study investigates a risk-optimized approach to ultracentral SBRT in an elderly and comorbid patient cohort. Patients and Methods Analysis encompassed 129 patients (mean age: 70 ± 11 years, median Charlson comorbidity index: 4 [range, 3-5]) following risk-adapted SBRT to central or ultracentral primary and secondary lung tumors between 2012 and 2019 (78 central, 51 ultracentral). Ultracentral tumors were defined by planning target volume overlap with the proximal bronchial tree. Whereas ultracentral tumors were treated with a risk-optimized fractionation scheme of 50 Gy in 10 fractions, central tumors received higher-fractionated 60 Gy in 8 fractions. Outcome parameters and toxicity for ultracentral and central tumors were assessed using Kaplan-Meier and competing risk analyses. Results Local failure rate was not significantly increased in ultracentral tumors compared with central tumors (2-year local failure rate ultracentral, 26.9%; 95% confidence interval [CI], 12.2%-44.2%; central, 14.6%; 95% CI, 6.6%-25.5%; P = .17). Overall survival was similar in both groups (2-year overall survival central, 55.4%; 95% CI, 44.5%-68.9%; ultracentral, 54.9%; 95% CI, 40.8%-73.9%; P = .6). Toxicity was moderate, with toxicity ≥ grade 3 rates of 15.3% (95% CI, 5.9%-28.9%) for ultracentral and 7.3% (95% CI, 2.7%-15.0%) for central tumors after 2 years (P = .27). No grade 4 toxicity and only 1 potential grade 5 toxicity were observed in the ultracentral cohort. Conclusion Risk-optimized SBRT to ultracentral lung tumors is a reasonably effective and safe treatment alternative in frail patients.