Patterns of Pretreatment Diagnostic Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Non-Small Cell Lung Cancer (NSCLC): Special Characteristics in the COVID Pandemic and Influence on Outcomes.

The pandemic raised a discussion about the postponement of medical interventions for non-small cell lung cancer (NSCLC). We analyzed the characteristics of pretreatment diagnostic assessment in the pandemic and the influence of diagnostic assessment on outcomes. A total of 96 patients with stereotactic body radiation therapy (SBRT) for NSCLC were included. The number of patients increased from mean 0.9 (2012-2019) to 1.45 per month in the COVID era (p < 0.05). Pandemic-related factors (contact reduction, limited intensive care unit resources) might have influenced clinical decision making towards SBRT. The time from pretreatment assessment (multidisciplinary tumor board decision, bronchoscopy, planning CT) to SBRT was longer during the COVID period (p < 0.05). Reduced services, staff shortage, or appointment management to mitigate infection risks might explain this finding. Overall survival, progression-free survival, locoregional progression-free survival, and distant progression-free survival were superior in patients who received a PET/CT scan prior to SBRT (p < 0.05). This supports that SBRT guidelines advocate the acquisition of a PET/CT scan. A longer time from PET/CT scan/conventional staging to SBRT (<10 vs. ≥10 weeks) was associated with worse locoregional control (p < 0.05). The postponement of diagnostic or therapeutic measures in the pandemic should be discussed cautiously. Patient- and tumor-related features should be evaluated in detail.

Assessment of Sodium MRI at 7 Tesla as Predictor of Therapy Response and Survival in Glioblastoma Patients.

The purpose of this work was to prospectively investigate sodium (23Na) MRI at 7 Tesla (T) as predictor of therapy response and survival in patients with glioblastoma (GBM). Thus, 20 GBM patients underwent 23Na MRI at 7T before, immediately after and 6 weeks after chemoradiotherapy (CRT). The median tissue sodium concentration (TSC) inside the whole tumor excluding necrosis was determined. Initial response to CRT was assessed employing the updated response assessment in neuro-oncology working group (RANO) criteria. Clinical parameters, baseline TSC and longitudinal TSC differences were compared between patients with initial progressive disease (PD) and patients with initial stable disease (SD) using Fisher's exact tests and Mann-Whitney-U-tests. Univariate proportional hazard models for progression free survival (PFS) and overall survival (OS) were calculated using clinical parameters and TSC metrics as predictor variables. The analyses demonstrated that TSC developed heterogeneously over all patients following CRT. None of the TSC metrics differed significantly between cases of initial SD and initial PD. Furthermore, TSC metrics did not yield a significant association with PFS or OS. Conversely, the initial response according to the RANO criteria could significantly predict PFS [univariate HR (95%CI) = 0.02 (0.0001-0.21), p < 0.001] and OS [univariate HR = 0.17 (0.04-0.65), p = 0.005]. In conclusion, TSC showed treatment-related changes in GBM following CRT, but did not significantly correlate with the initial response according to the RANO criteria, PFS or OS. In contrast, the initial response according to the RANO criteria was a significant predictor of PFS and OS. Future investigations need to elucidate the reasons for treatment-related changes in TSC and their clinical value for response prediction in glioblastoma patients receiving CRT.

Improving the modelling of irradiation-induced brain activation for in vivo PET verification of proton therapy.

BACKGROUND AND PURPOSES: A reliable Monte Carlo prediction of proton-induced brain tissue activation used for comparison to particle therapy positron-emission-tomography (PT-PET) measurements is crucial for in vivo treatment verification. Major limitations of current approaches to overcome include the CT-based patient model and the description of activity washout due to tissue perfusion. MATERIAL AND METHODS: Two approaches were studied to improve the activity prediction for brain irradiation: (i) a refined patient model using tissue classification based on MR information and (ii) a PT-PET data-driven refinement of washout model parameters. Improvements of the activity predictions compared to post-treatment PT-PET measurements were assessed in terms of activity profile similarity for six patients treated with a single or two almost parallel fields delivered by active proton beam scanning. RESULTS: The refined patient model yields a generally higher similarity for most of the patients, except in highly pathological areas leading to tissue misclassification. Using washout model parameters deduced from clinical patient data could considerably improve the activity profile similarity for all patients. CONCLUSIONS: Current methods used to predict proton-induced brain tissue activation can be improved with MR-based tissue classification and data-driven washout parameters, thus providing a more reliable basis for PT-PET verification.

Generation of a New Disease-specific Prognostic Score for Patients With Brain Metastases From Small-cell Lung Cancer Treated With Whole Brain Radiotherapy (BMS-Score) and Validation of Two Other Indices.

INTRODUCTION: Patients with small-cell lung cancer (SCLC) demonstrate an exception in the treatment of brain metastases (BM), because in patients with SCLC whole brain radiotherapy (WBRT) only is the preferred treatment modality. The purpose of this study was to develop a prognostic score for patients with brain metastases from SCLC treated with WBRT. PATIENTS AND METHODS: The present study was conducted utilizing a single-institution, previously described, retrospective database of patients with SCLC who were treated with WBRT (n = 221). Univariate and multivariate analyses were performed to generate the "brain metastases from SCLC score" (BMS score) based on favorable prognostic factors: Karnofsky performance status (KPS > 70), extracerebral disease status (stable disease/controlled), and time of appearance of BM (synchronous). Furthermore, the disease-specific graded prognostic assessment score as well as the recursive partitioning analysis (RPA) were performed and compared with the new BMS score by using the log-rank (Mantel-Cox) test. RESULTS: BMS score and RPA showed the most significant differences between classes (P < .001). BMS score revealed a mean overall survival (OS) of 2.62 months in group I (0-1 points), 6.61 months in group II (2-3 points), and 12.31 months in group III (4 points). The BMS score also identified the group with the shortest survival (2.62 months in group I), and the numbers of patients in each group were most equally distributed with the BMS score. CONCLUSION: The new BMS score was more prognostic than the RPA and disease-specific graded prognostic assessment scores. The BMS score is easy to use and reflects known prognostic factors in contemporary patients with SCLC treated with WBRT. Future studies are necessary to validate these findings.

Clinical implementation and range evaluation of in vivo PET dosimetry for particle irradiation in patients with primary glioma.

PURPOSE: The physical and biological properties of ion-beams offer various advantages in comparison to conventional radiotherapy, though uncertainties concerning quality assurance are still left. Due to the inverted depth dose profile, range accuracy is of paramount importance. We investigated the range deviations between planning simulation and post-fractional PET/CT measurement from particle therapy in primary glioblastoma. METHODS AND MATERIALS: 20 patients with glioblastoma undergoing particle therapy at our institution were selected. 10 received a proton-boost, 10 a carbon-ion-boost in addition to standard treatment. After two fractions, we performed a PET/CT-scan of the brain. We compared the resulting range deviation based on the Most-likely-shift method between the two measurements, and the measurements with corresponding expectations, calculated with the Monte-Carlo code FLUKA. RESULTS: A patient's two measurements deviated by 0.7mm (±0.7mm). Overall comparison between measurements and simulation resulted in a mean range deviation of 3.3mm (±2.2mm) with significant lower deviations in the (12)C-arm. CONCLUSION: The used planning concepts display the actual dose distributions adequately. The carbon ion group's results are below the used PTV safety margins (3mm). Further adjustments to the simulation are required for proton irradiations. Some anatomical situations require particular attention to ensure highest accuracy and safety.

Assessment of early toxicity and response in patients treated with proton and carbon ion therapy at the Heidelberg ion therapy center using the raster scanning technique.

UNLABELLED: PUROPOSE: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. PATIENTS AND METHODS: Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. RESULTS: In all 118 patients, few side effects were observed, in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. CONCLUSIONS: Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility.