Phase 3 Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampus Avoidance in SCLC (NCT01780675)

Introduction: To compare neurocognitive functioning in patients with SCLC who received prophylactic cranial irradiation (PCI) with or without hippocampus avoidance (HA). Methods: In a multicenter, randomized phase 3 trial (NCT01780675), patients with SCLC were randomized to standard PCI or HA-PCI of 25 Gy in 10 fractions. Neuropsychological tests were performed at baseline and 4, 8, 12, 18, and 24 months after PCI. The primary end point was total recall on the Hopkins Verbal Learning Test-Revised at 4 months; a decline of at least five points from baseline was considered a failure. Secondary end points included other cognitive outcomes, evaluation of the incidence, location of brain metastases, and overall survival. Results: From April 2013 to March 2018, a total of 168 patients were randomized. The median follow-up time was 26.6 months. In both treatment arms, 70% of the patients had limited disease and baseline characteristics were well balanced. Decline on the Hopkins Verbal Learning Test-Revised total recall score at 4 months was not significantly different between the arms: 29% of patients on PCI and 28% of patients on HA-PCI dropped greater than or equal to five points (p = 1.000). Performance on other cognitive tests measuring memory, executive function, attention, motor function, and processing speed did not change significantly different over time between the groups. The overall survival was not significantly different (p = 0.43). The cumulative incidence of brain metastases at 2 years was 20% (95% confidence interval: 12%-29%) for the PCI arm and 16% (95% confidence interval: 7%-24%) for the HA-PCI arm. Conclusions: This randomized phase 3 trial did not find a lower probability of cognitive decline in patients with SCLC receiving HA-PCI compared with conventional PCI. No increase in brain metastases at 2 years was observed in the HA-PCI arm. (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved

Refining Critical Structure Contouring in STereotactic Arrhythmia Radioablation (STAR): Benchmark Results and Consensus Guidelines from the STOPSTORM.eu Consortium.

BACKGROUND AND PURPOSE In patients with recurrent ventricular tachycardia (VT), STereotactic Arrhythmia Radioablation (STAR) shows promising results. The STOPSTORM consortium was established to investigate and harmonise STAR treatment in Europe. The primary goals of this benchmark study were to standardise contouring of organs at risk (OAR) for STAR, including detailed substructures of the heart, and accredit each participating centre. MATERIALS AND METHODS Centres within the STOPSTORM consortium were asked to delineate 31 OAR in three STAR cases. Delineation was reviewed by the consortium expert panel and after a dedicated workshop feedback and accreditation was provided to all participants. Further quantitative analysis was performed by calculating DICE similarity coefficients (DSC), median distance to agreement (MDA), and 95th percentile distance to agreement (HD95). RESULTS Twenty centres participated in this study. Based on DSC, MDA and HD95, the delineations of well-known OAR in radiotherapy were similar, such as lungs (median DSC=0.96, median MDA=0.1mm and median HD95=1.1mm) and aorta (median DSC=0.90, median MDA=0.1mm and median HD95=1.5mm). Some centres did not include the gastro-oesophageal junction, leading to differences in stomach and oesophagus delineations. For cardiac substructures, such as chambers (median DSC=0.83, median MDA=0.2mm and median HD95=0.5mm), valves (median DSC=0.16, median MDA=4.6mm and median HD95=16.0mm), coronary arteries (median DSC=0.4, median MDA=0.7mm and median HD95=8.3mm) and the sinoatrial and atrioventricular nodes (median DSC=0.29, median MDA=4.4mm and median HD95=11.4mm), deviations between centres occurred more frequently. After the dedicated workshop all centres were accredited and contouring consensus guidelines for STAR were established. CONCLUSION This STOPSTORM multi-centre critical structure contouring benchmark study showed high agreement for standard radiotherapy OAR. However, for cardiac substructures larger disagreement in contouring occurred, which may have significant impact on STAR treatment planning and dosimetry evaluation. To standardize OAR contouring, consensus guidelines for critical structure contouring in STAR were established

Four-dimensional computed tomographic analysis of esophageal mobility during normal respiration

BACKGROUND: Chemo-radiotherapy for thoracic tumors can result in high-grade radiation esophagitis. Treatment planning to reduce esophageal irradiation requires organ motion to be accounted for. In this study, esophageal mobility was assessed using four-dimensional computed tomography (4DCT). METHODS AND MATERIALS: Thoracic 4DCT scans were acquired on a 16-slice CT scanner in 29 patients. The outer esophageal wall was contoured in two extreme phases of respiration in 9 patients with nonesophageal malignancies. The displacement of the center of contour was measured at 2-cm intervals. In 20 additional patients with Stage I lung cancer, the esophagus was contoured in all 10 phases of each 4DCT at five defined anatomic levels. Both approaches were then applied to 4DCT scans of 4 patients who each had two repeat scans performed. A linear mixed effects model was constructed with fixed effects: measurement direction, measurement type, and measurement location along the cranio-caudal axis. RESULTS: Measurement location and direction were significant descriptive parameters (Wald F-tests, p <0.001), and the interaction term between the two was significant (p = 0.02). Medio-lateral mobility exceeded dorso-ventral mobility in the lower half of the esophagus but was of a similar magnitude in the upper half. Margins that would have incorporated all movement in medio-lateral and dorso-ventral directions were 5 mm proximally, 7 mm and 6 mm respectively in the mid-esophagus, and 9 mm and 8 mm respectively in the distal esophagus. CONCLUSIONS: The distal esophagus shows more mobility. Margins for mobility that can encompass all movement were derived for use in treatment planning, particularly for stereotactic radiotherap

BETER na hodgkinlymfoom; nazorg op maat voor langetermijneffecten van de behandeling

The Dutch BETER consortium has established a national care infrastructure for Hodgkin lymphoma survivors. 'BETER' [the Dutch word for 'better'] stands for Better care after Hodgkin lymphoma (HL): Evaluation of long-term Treatment Effects and screening Recommendations. The survivorship care focuses on long-term effects of HL treatment. Over 10,000 HL survivors who were treated in the period spanning 1965-2008 have been identified. As part of the survivorship care initiative, specific BETER out-patient clinics have been set up. A dedicated website, www.beternahodgkin.nl, provides HL survivors with relevant information. The stakeholders of the BETER survivorship care programme aim to achieve an improved healthy life expectancy for patients treated for HL

Standardizing the Cardiac Radioablation Targeting Workflow: Enabling Semi-Automated Angulation and Segmentation of the Heart According to the American Heart Association Segmented Model

Purpose: Cardiac radioablation has evolved as a potential treatment modality for therapy-refractory ventricular tachycardia. To standardize cardiac radioablation treatments, promote accurate communication and target identification, and to assess toxicity, robust, and reproducible methods for angulation and cardiac segmentation are paramount. In this study, we developed and evaluated a tool for semiautomated angulation and segmentation according to the American Heart Association 17-segment model. Methods and Materials: The semiautomated angulation and segmentation of the planning-computed tomography (CT) was based on an in-house developed tool requiring placement of only 4 point-markers and a rotation matrix. For angulation, 2 markers defining the cardiac long-axis were placed: at the cardiac apex and at the center of the mitral valve. A rotation matrix was derived that angulates the CT volume, resulting in the cardiac short axis. Segmentation was subsequently performed based on marking the 2 left ventricular hinge points. To evaluate reproducibility, 5 observers independently placed markers in planning CTs of 6 patients. Results: The root mean square of the standard deviation for the angulation and segmentation marker positions were ≤0.5 cm. The 17 segments were subsequently generated and compared between the observers resulting in a median Dice coefficient of 0.8 (interquartile range: 0.70-0.87) and a median of the mean Hausdorff distance of 0.09 cm (interquartile range: 0.05-0.17). The interquartile ranges of Euler angles α and β, determined by the angulation markers, was less than 3 degrees for all patients except one. For the γ angle, determined by the hinge point markers, the interquartile range was up to 12 degrees. Conclusions: In this study a method for semiautomatic angulation and segmentation of the heart for cardiac radioablation according to the American Heart Association Segmented Model is presented and evaluated. Based on our results we believe that the segmentation is reproducible and that it can be used to promote communication between radiation oncology and cardiology, enables cardiology-oriented targeting and permits focused toxicity evaluations

Improved progression free survival for patients with diabetes and locally advanced non-small cell lung cancer (NSCLC) using metformin during concurrent chemoradiotherapy

The aim was to investigate whether the use of metformin during concurrent chemoradiotherapy (cCRT) for locally advanced non-small cell lung cancer (NSCLC) improved treatment outcome. A total of 682 patients were included in this retrospective cohort study (59 metformin users, 623 control patients). All received cCRT in one of three participating radiation oncology departments in the Netherlands between January 2008 and January 2013. Primary endpoint was locoregional recurrence free survival (LRFS), secondary endpoints were overall survival (OS), progression-free survival (PFS) and distant metastasis free survival (DMFS). No significant differences in LRFS or OS were found. Metformin use was associated with an improved DMFS (74% versus 53% at 2years; p=0.01) and PFS (58% versus 37% at 2years and a median PFS of 41months versus 15months; p=0.01). In a multivariate cox-regression analysis, the use of metformin was a statistically significant independent variable for DMFS and PFS (p=0.02 and 0.03). Metformin use during cCRT is associated with an improved DMFS and PFS for locally advanced NSCLC patients, suggesting that metformin may be a valuable treatment addition in these patients. Evidently, our results merit to be verified in a prospective tria

Additional weekly Cetuximab to concurrent chemoradiotherapy in locally advanced non-small cell lung carcinoma: efficacy and safety outcomes of a randomized, multi-center phase II study investigating

Modest benefits from concurrent chemoradiotherapy in patients with locally advanced NSCLC warrant further clinical investigations to identify more effective treatment regimens. Cetuximab, a monoclonal antibody against the epidermal growth factor receptor has shown activity in NSCLC. We report on the safety and efficacy of the combination of daily dose Cisplatin and concurrent radiotherapy with or without weekly Cetuximab. Patients received high dose accelerated radiotherapy (66 Gy in 24 fractions) and concurrent daily Cisplatin (6 mg/m(2)) without (Arm A) or with (Arm B) weekly Cetuximab (400 mg/m(2) loading dose one week prior to radiotherapy followed by weekly 250 mg/m(2)). The primary endpoint of the trial was objective local control rate (OLCR) determined at 6-8 weeks after treatment. Toxicity was reported as well. Between February 2009 and May 2011, 102 patients were randomized. Median follow up was 29 months. The OLCR was 84% in Arm A and 92% in Arm B (p=0.36). The one-year local progression free interval (LPFI) and overall survival (OS) were 69% and 82% for Arm A and 73% and 71% for Arm B, respectively (LPFI p=0.39; OS p=0.99). Toxicity compared equally between both groups. The addition of Cetuximab to radiotherapy and concurrent Cisplatin did not improve disease control in patients with locally advanced NSCLC but increased treatment related toxicit