Intensity-modulated radiotherapy at high-volume centers improves survival in patients with esophageal adenocarcinoma receiving trimodality therapy.

The standard of care trimodality therapy for resectable locally advanced esophageal adenocarcinoma is complex and necessitates multidisciplinary care and expertise. In this work, it is hypothesized that facility clinical volume and utilization of intensity-modulated radiotherapy (IMRT) may influence outcomes. The National Cancer Data Base was queried for patients with cT1-4-N0-3 M0 esophageal adenocarcinoma undergoing trimodality therapy from 2004 to 2013 (n = 2445). All patients received chemoradiation followed by esophagectomy at a Commission on Cancer facility. The facility volume was categorized into tertiles: high-volume centers (HVCs) in the highest 25th percentile of cases per year, intermediate-volume centers (IVCs) with the next highest 25th percentile of cases, and low- and very low-volume centers (LVCs) in the lowest 50th percentile. Overall survival (OS) was estimated using Kaplan-Meier methods and Cox proportional hazard regression. Propensity score matching to balance patient characteristics between volume centers was performed. Subgroup analysis was done comparing IMRT versus 3D conformal radiotherapy. The median follow-up was 26 months. Treatment at an HVC (hazard ratio 0.63, 95% CI 0.49-0.81, P < 0.001) was found to be independently associated with improved overall survival in multivariable analysis. Three-year OS was 58.4%, 46.2%, and 47.5% for HVCs, IVCs, and LVCs, respectively (P < 0.001). Patients at HVCs were more likely to receive IMRT over 3D chemoradiation (CRT; OR 3.45, 95% CI 2.4-5.0, P < 0.001). Patients treated using IMRT at HVCs had improved OS compared to those treated at IVCs or LVCs (HR 0.68, 95% CI 0.52-0.90, P < 0.01), while patients treated with 3D CRT at HVCs had no survival advantage over those at IVCs or LVCs (P = 0.28). Patients with locally advanced esophageal adenocarcinoma treated with IMRT and at HVCs appear to have improved survival.

Dose escalated neoadjuvant chemoradiotherapy with dose-painting intensity-modulated radiation therapy and improved pathologic complete response in locally advanced esophageal cancer.

We compared pathologic complete response (pCR) rate, toxicity, and postoperative complications between patients treated preoperatively with 50.4 Gy versus dose escalation with dose-painting intensity-modulated radiation therapy (dp-IMRT) to 56 Gy in locally advanced esophageal cancer. We evaluated esophageal cancer patients treated between 2006 and 2014 with preoperative IMRT chemoradiation to a dose of 50.4 Gy versus 56 Gy. The endpoints were pCR and toxicity. We identified 113 patients (50.4 Gy: n = 40; 56 Gy: n = 73). There were no significant differences in tumor or patient characteristics. Patients treated with 56 Gy demonstrated a higher pCR rate (56.2% vs. 30.0%) and lower pathologic nonresponse rate (4.1% vs. 20.0%) compared to patients treated to 50.4 Gy (P = 0.008). This remained significant on multivariate analysis (OR 3.375 95%CI 1.3-8.8, P = 0.013). Patients treated to 56 Gy also had an improved 3-year locoregional control rate compared to those treated to 50.4 Gy (93.8% vs. 78.5%; P = 0.022). The estimated 3-year freedom from failure was also superior in the 56 Gy arm (73.7% vs. 52.2%; P = 0.051), approaching significance. There were no differences in treatment related grade ≥3 toxicities, hospital admissions, feeding tube, esophageal stent placement, or dilation. There was, however, a statistically significant increase in postoperative atrial fibrillation in patients treated with 56 Gy (30.1% vs. 12.5%; P = 0.036). There was no difference in postoperative 30 or 60 day mortality. Dose escalation to 56 Gy with dp-IMRT is safe and results in significantly higher complete pathologic response rates in esophageal cancer without an increase in treatment-related toxicity. Prospective trials using dp-IMRT are needed to address the role of dose escalation on pCR rate and survival in esophageal cancer.

Delta radiomics analysis of Magnetic Resonance guided radiotherapy imaging data can enable treatment response prediction in pancreatic cancer.

BACKGROUND: Magnetic Resonance Image guided Stereotactic body radiotherapy (MRgRT) is an emerging technology that is increasingly used in treatment of visceral cancers, such as pancreatic adenocarcinoma (PDAC). Given the variable response rates and short progression times of PDAC, there is an unmet clinical need for a method to assess early RT response that may allow better prescription personalization. We hypothesize that quantitative image feature analysis (radiomics) of the longitudinal MR scans acquired before and during MRgRT may be used to extract information related to early treatment response. METHODS: Histogram and texture radiomic features (n = 73) were extracted from the Gross Tumor Volume (GTV) in 0.35T MRgRT scans of 26 locally advanced and borderline resectable PDAC patients treated with 50 Gy RT in 5 fractions. Feature ratios between first (F1) and last (F5) fraction scan were correlated with progression free survival (PFS). Feature stability was assessed through region of interest (ROI) perturbation. RESULTS: Linear normalization of image intensity to median kidney value showed improved reproducibility of feature quantification. Histogram skewness change during treatment showed significant association with PFS (p = 0.005, HR = 2.75), offering a potential predictive biomarker of RT response. Stability analyses revealed a wide distribution of feature sensitivities to ROI delineation and was able to identify features that were robust to variability in contouring. CONCLUSIONS: This study presents a proof-of-concept for the use of quantitative image analysis in MRgRT for treatment response prediction and providing an analysis pipeline that can be utilized in future MRgRT radiomic studies.