Phase II Trial of Flaxseed to Prevent Acute Complications After Chemoradiation for Lung Cancer.

Background: Thoracic radiotherapy is complicated by acute radiation-induced adverse events such as radiation pneumonitis (RP) and radiation esophagitis (RE). Based on preclinical work and a randomized pilot trial from our laboratory, this single-arm phase II trial investigated administering flaxseed as a radioprotector in patients receiving definitive chemoradiation for nonsmall cell lung cancer (NSCLC). Methods: Between June 2015 and February 2018, 33 patients with locally advanced or metastatic NSCLC with planned definitive chemoradiation were enrolled. Finely-ground Linum usitatissimum L. (Linaceae; flaxseed or linseed) in 40-g packets were provided for daily consumption in any patient-desired formulation 1 week before radiotherapy and throughout radiotherapy as tolerated. The primary outcomes were overall adverse events, with particular focus on Grade ≥3 RP, and flaxseed tolerability. Adverse events were graded according to CTCAE v4.0. Results: Of the 33 patients enrolled, 5 patients (15%) did not receive chemoradiation, 4 (12%) withdrew promptly after enrollment, 4 (12%) did not return a flaxseed consumption log, and 1 patient had irritable bowel syndrome (3%). The remaining 19 patients (57%) had chemoradiation and flaxseed ingestion with a mean completion and standard deviation of the intended flaxseed course of 62% ± 8.3%. Nine (50%) of these 19 patients reported difficulties with flaxseed consumption, citing nausea, constipation, odynophagia, or poor taste or texture. One patient (5%), with unverifiable flaxseed consumption, developed Grade 3 RP. There were no cases of Grade 2 RP. Six patients (32%) developed Grade 2 RE, but no patients developed Grade ≥3 RE. Median overall and progression-free survival were 31 and 12 months, respectively. Conclusions: Despite the low incidence of acute radiation-induced complications reported, significant treatment-related gastrointestinal toxicities and subsequently low flaxseed tolerability inhibit accurate determination of flaxseed effect in patients receiving concurrent thoracic chemoradiation. Thus, further investigations should focus on optimizing flaxseed formulation for improved tolerability and evaluation. ClinicalTrials.gov ID: NCT02475330.

Multiblock Discriminant Analysis of Integrative 18F-FDG-PET/CT Radiomics for Predicting Circulating Tumor Cells in Early-Stage Non-small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy.

PURPOSE: The main objective of the present study was to integrate 18F-FDG-PET/CT radiomics with multiblock discriminant analysis for predicting circulating tumor cells (CTCs) in early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic body radiation therapy (SBRT). METHODS: Fifty-six patients with stage I NSCLC treated with SBRT underwent 18F-FDG-PET/CT imaging pre-SBRT and post-SBRT (median, 5 months; range, 3-10 months). CTCs were assessed via a telomerase-based assay before and within 3 months after SBRT and dichotomized at 5 and 1.3 CTCs/mL. Pre-SBRT, post-SBRT, and delta PET/CT radiomics features (n = 1548 × 3/1562 × 3) were extracted from gross tumor volume. Seven feature blocks were constructed including clinical parameters (n = 12). Multiblock data integration was performed using block sparse partial least squares-discriminant analysis (sPLS-DA) referred to as Data Integration Analysis for Biomarker Discovery Using Latent Components (DIABLO) for identifying key signatures by maximizing common information between different feature blocks while discriminating CTC levels. Optimal input blocks were identified using a pairwise combination method. DIABLO performance for predicting pre-SBRT and post-SBRT CTCs was evaluated using combined AUC (area under the curve, averaged across different blocks) analysis with 20 × 5-fold cross-validation (CV) and compared with that of concatenation-based sPLS-DA that consisted of combining all features into 1 block. CV prediction scores between 1 class versus the other were compared using the Wilcoxon rank sum test. RESULTS: For predicting pre-SBRT CTCs, DIABLO achieved the best performance with combined pre-SBRT PET radiomics and clinical feature blocks, showing CV AUC of 0.875 (P = .009). For predicting post-SBRT CTCs, DIABLO achieved the best performance with combined post-SBRT CT and delta CT radiomics feature blocks, showing CV AUCs of 0.883 (P = .001). In contrast, all single-block sPLS-DA models could not attain CV AUCs higher than 0.7. CONCLUSIONS: Multiblock integration with discriminant analysis of 18F-FDG-PET/CT radiomics has the potential for predicting pre-SBRT and post-SBRT CTCs. Radiomics and CTC analysis may complement and together help guide the subsequent management of patients with ES-NSCLC.

Higher Dose Volumes May Be Better for Evaluating Radiation Pneumonitis in Lung Proton Therapy Patients Compared With Traditional Photon-Based Dose Constraints.

PURPOSE: The dosimetric parameters used clinically to reduce the likelihood of radiation pneumonitis (RP) for lung cancer radiation therapy have traditionally been V20Gy ≤ 30% to 35% and mean lung dose ≤ 20 to 23 Gy; however, these parameters are derived based on studies from photon therapy. The purpose of this study is to evaluate whether such dosimetric predictors for RP are applicable for locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with proton therapy. METHODS AND MATERIALS: In the study, 160 (78 photon, 82 proton) patients with LA-NSCLC treated with chemoradiotherapy between 2011 and 2016 were retrospectively identified. Forty (20 photon, 20 proton) patients exhibited grade ≥2 RP after therapy. Dose volume histograms for the uninvolved lung were extracted for each patient. The percent lung volumes receiving above various dose levels were obtained in addition to V20Gy and Dmean. These dosimetric parameters and patient characteristics were evaluated with univariate and multivariate logistic regression tests. Receiver operating characteristic curves were generated to obtain the optimal dosimetric constraints through analyzing RP and non-RP sensitivity and specificity values. RESULTS: The multivariate analysis showed V40Gy and Dmean to be statistically significant for proton and photon patients, respectively. V35Gy to V50Gy were strongly correlated to V40Gy for proton patients. Based on the receiver operating characteristic curves, V35Gy to V50Gy had the highest area under the curve compared with other dose levels for proton patients. A potential dosimetric constraint for RP predictor in proton patients is V40Gy ≤ 23%. CONCLUSIONS: In addition to V20Gy and Dmean, the lung volume receiving higher doses, such as V40Gy, may be used as an additional indicator for RP in LA-NSCLC patients treated with proton therapy.

Efficacy and safety of stereotactic body radiation therapy for the treatment of pulmonary metastases from sarcoma: A potential alternative to resection.

BACKGROUND/OBJECTIVES: Oligometastatic sarcoma pulmonary metastases (PM) are typically treated with resection and/or chemotherapy. We hypothesize that stereotactic body radiotherapy (SBRT) can be an alternative to surgery that can achieve high rates of local control (LC) with limited toxicity. METHODS: Thirty consecutive sarcoma patients received SBRT to 39 PM's from 2011 to 2015 at two university hospitals to a median dose of 50 Gy in 4-5 fractions with CyberKnife or linear accelerator. Patients underwent CT or PET/CT scans q3 months after SBRT. RESULTS: 77% received prior chemotherapy, 70% had 1-3 prior pulmonary resections, and 26% received prior thoracic radiotherapy. Median lesion size was 2.4 cm (range 0.5-8.1 cm). Median follow-up was 16 and 23 months for patients alive at last follow-up. At 12 and 24 months, LC was 94% and 86%, and OS was 76% and 43%. LC and OS did not differ by SBRT technique, fractionation regimen, lesion location, histology, or size (all P > 0.05). Three developed grade 2 chest-wall toxicity with no other grade ≥2 toxicities. CONCLUSIONS: This is the largest series on SBRT for sarcoma PM's and demonstrates that SBRT is well-tolerated with excellent LC across tumor locations and sizes. SBRT should be considered in these patients, and prospective studies are warranted. J. Surg. Oncol. 2016;114:65-69. © 2016 Wiley Periodicals, Inc.

Dose-Escalated Irradiation and Overall Survival in Men With Nonmetastatic Prostate Cancer.

IMPORTANCE: In 5 published randomized clinical trials, dose-escalated external-beam radiation therapy (EBRT) for prostate cancer resulted in improved biochemical and local control. However, scarce evidence addresses whether dose escalation improves overall survival. OBJECTIVE: To examine the association between dose-escalated EBRT and overall survival among men with nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective, nonrandomized comparative effectiveness study of dose-escalated vs standard-dose EBRT for prostate cancer diagnosed from 2004 to 2006 using the National Cancer Database (NCDB), which includes data from patients treated at Commission on Cancer-accredited community, academic, and comprehensive cancer facilities. Three cohorts were evaluated: men with low-risk (n = 12,229), intermediate-risk (n = 16,714), or high-risk (n = 13,538) prostate cancer. EXPOSURES: We categorized patients in each risk cohort into 2 treatment groups: standard-dose (from 68.4 Gy to <75.6 Gy) or dose-escalated (≥75.6 Gy to 90 Gy) EBRT (1 Gy = 100 rad). MAIN OUTCOMES AND MEASURES: We compared overall survival between treatment groups in each analytic cohort using Cox proportional hazard models with an inverse probability weighted propensity score (IPW-PS) approach. In secondary analyses, we evaluated dose response for survival. RESULTS: Dose-escalated EBRT was associated with improved survival in the intermediate-risk (IPW-PS adjusted hazard ratio [HR], 0.84; 95% CI, 0.80-0.88; P < .001) and high-risk groups (HR, 0.82; 95% CI, 0.78-0.85; P < .001) but not the low-risk group (HR, 0.98; 95% CI, 0.92-1.05; P = .54). For every incremental increase of about 2 Gy in dose, there was a 7.8% (95% CI, 5.4%-10.2%; P < .001) and 6.3% (95% CI, 3.3%-9.1%; P < .001) reduction in the hazard of death for intermediate- and high-risk patients, respectively. CONCLUSIONS AND RELEVANCE: Dose-escalated EBRT is associated with improved overall survival in men with intermediate- and high-risk prostate cancer but not low-risk prostate cancer. These results add to the evidence questioning aggressive local treatment strategies in men with low-risk prostate cancer but supporting such treatment in men with greater disease severity.