Treatment utilization and outcomes in elderly patients with locally advanced esophageal carcinoma: A review of the National Cancer Database

For elderly patients with locally advanced esophageal cancer, therapeutic approaches and outcomes in a modern cohort are not well characterized. Patients ≥70 years old with clinical stage II and III esophageal cancer diagnosed between 1998 and 2012 were identified from the National Cancer Database and stratified based on treatment type. Variables associated with treatment utilization were evaluated using logistic regression and survival evaluated using Cox proportional hazards analysis. Propensity matching (1:1) was performed to help account for selection bias. A total of 21,593 patients were identified. Median and maximum ages were 77 and 90, respectively. Treatment included palliative therapy (24.3%), chemoradiation (37.1%), trimodality therapy (10.0%), esophagectomy alone (5.6%), or no therapy (12.9%). Age ≥80 (OR 0.73), female gender (OR 0.81), Charlson-Deyo comorbidity score ≥2 (OR 0.82), and high-volume centers (OR 0.83) were associated with a decreased likelihood of palliative therapy versus no treatment. Age ≥80 (OR 0.79) and Clinical Stage III (OR 0.33) were associated with a decreased likelihood, while adenocarcinoma histology (OR 1.33) and nonacademic cancer centers (OR 3.9), an increased likelihood of esophagectomy alone compared to definitive chemoradiation. Age ≥80 (OR 0.15), female gender (OR 0.80), and non-Caucasian race (OR 0.63) were associated with a decreased likelihood, while adenocarcinoma histology (OR 2.10) and high-volume centers (OR 2.34), an increased likelihood of trimodality therapy compared to definitive chemoradiation. Each treatment type demonstrated improved survival compared to no therapy: palliative treatment (HR 0.49) to trimodality therapy (HR 0.25) with significance between all groups. Any therapy, including palliative care, was associated with improved survival; however, subsets of elderly patients with locally advanced esophageal cancer are less likely to receive aggressive therapy. Care should be taken to not unnecessarily deprive these individuals of treatment that may improve survival

A single-institution phase I feasibility study of dose-escalated IMRT for non-operative locally advanced esophageal carcinoma

•Dose escalation with IMRT to 60 Gy for esophageal cancer is feasible.•Dose escalation with cisplatin/5-FU still results in significant toxicity.•Improved local control, but comparable survival compared to historical controls.•Pretreatment weight loss was found to be an independent predictor of poor survival.•Our dose escalation study is one of few with predominant adenocarcinoma histology. Radiation dose escalation to improve poor outcomes with chemoradiation in locally advanced esophageal carcinoma is limited in part by increased toxicity. This Phase I study investigates the use of IMRT to improve tolerability of dose escalation. A single-institution, prospective study was conducted between 2007 and 2013 for individuals with inoperable esophageal carcinoma. Gross disease received 60 Gy in 30 fractions and at-risk sites received 54 Gy with simultaneous integrated boost. Concurrent chemotherapy primarily consisted of cisplatin/5-FU. The primary objective was to assess feasibility (<15% rate of grade 4–5 toxicity). Secondary objectives included assessment of overall survival (OS), progression free survival (PFS), and locoregional (LRR) and distant recurrence. Twenty-six patients were enrolled with median follow up of 17.6 months (range 0.1 to 152.0). The majority were AJCC 7th edition Stage III (54%), distal esophagus primary (81%), and adenocarcinoma histology (85%). Twenty-one patients (81%) completed their course of radiation therapy, while only 55% received 2 cycles of concurrent cisplatin/5-FU. One grade 5 and one grade 4 cardiac event occurred, both during chemoradiation and before receiving 50 Gy. The 3-year OS was 48.6% (95% CI: 32.5 to 72.2%) and PFS was 28.5% (95% CI: 14.6 to 55.5%). Half developed distant failure with LRR occurring in 10 patients (38%), isolated in 5 patients. While feasibility was demonstrated, toxicity and compliance remained limiting factors with outcomes similar to historical controls. There remains an uncertain role for dose escalation in definitive management of locally advanced esophageal cancer

Pre-radiotherapy ctDNA liquid biopsy for risk stratification of oligometastatic non-small cell lung cancer

Abstract The optimal treatment paradigm for patients with oligometastatic non-small cell lung cancer (NSCLC) remains unclear. Some patients with oligometastatic disease experience prolonged remission after locally consolidative radiation therapy (RT), while others harbor micrometastatic disease (below limits of detection by imaging) and benefit from systemic therapy. To risk-stratify and identify the patients most likely to benefit from locally consolidative RT, we performed a multi-institutional cohort study of 1487 patients with oligometastatic NSCLC undergoing liquid biopsy analysis of circulating tumor DNA (ctDNA). In total, 1880 liquid biopsies were performed and approximately 20% of patients (n = 309) had ctDNA measured prior to RT and after their diagnosis of oligometastatic disease. Patients with undetectable ctDNA (pathogenic or likely pathogenic variants in plasma using the Tempus xF assay) before RT had significantly improved progression-free survival (PFS) (P = 0.004) and overall survival (OS) (P = 0.030). ctDNA maximum variant allele frequency (VAF) pre-RT and ctDNA mutational burden pre-RT were both significantly inversely correlated with PFS (maximum VAF P = 0.008, mutational burden P = 0.003) and OS (maximum VAF P = 0.007, mutational burden P = 0.045). These findings were corroborated by multivariate Cox proportional hazards models that included eight additional clinical and genomic parameters. Overall, these data suggest that in patients with oligometastatic NSCLC, pre-RT ctDNA can potentially identify the patients most likely to benefit from locally consolidative RT and experience prolonged PFS and OS. Similarly, ctDNA may be useful to identify undiagnosed micrometastatic disease where it may be appropriate to prioritize systemic therapies

Initial clinical experience building a dual CT- and MR-guided adaptive radiotherapy program

Introduction: Our institution was the first in the world to clinically implement MR-guided adaptive radiotherapy (MRgART) in 2014. In 2021, we installed a CT-guided adaptive radiotherapy (CTgART) unit, becoming one of the first clinics in the world to build a dual-modality ART clinic. Herein we review factors that lead to the development of a high-volume dual-modality ART program and treatment census over an initial, one-year period. Materials and Methods: The clinical adaptive service at our institution is enabled with both MRgART (MRIdian, ViewRay, Inc, Mountain View, CA) and CTgART (ETHOS, Varian Medical Systems, Palo Alto, CA) platforms. We analyzed patient and treatment information including disease sites treated, radiation dose and fractionation, and treatment times for patients on these two platforms. Additionally, we reviewed our institutional workflow for creating, verifying, and implementing a new adaptive workflow on either platform. Results: From October 2021 to September 2022, 256 patients were treated with adaptive intent at our institution, 186 with MRgART and 70 with CTgART. The majority (106/186) of patients treated with MRgART had pancreatic cancer, and the most common sites treated with CTgART were pelvis (23/70) and abdomen (20/70). 93.0% of treatments on the MRgART platform were stereotactic body radiotherapy (SBRT), whereas only 72.9% of treatments on the CTgART platform were SBRT. Abdominal gated cases were allotted a longer time on the CTgART platform compared to the MRgART platform, whereas pelvic cases were allotted a shorter time on the CTgART platform when compared to the MRgART platform. Our adaptive implementation technique has led to six open clinical trials using MRgART and seven using CTgART. Conclusions: We demonstrate the successful development of a dual platform ART program in our clinic. Ongoing efforts are needed to continue the development and integration of ART across platforms and disease sites to maximize access and evidence for this technique worldwide