AbstractQuantification and detection of circulating tumor DNA (ctDNA) has been used to identify the presence of cancers. Ablative radiation therapy kills tumor cells to reduce tumor burden and it follows that these dying tumor cells could lead to increased ctDNA abundance. We carried out deep, error-corrected sequencing of cell-free DNA collected serially from 12 stage I, and 2 stage II/III non-small cell lung cancer (NSCLC) patients undergoing external-beam radiation treatment (EBRT) after initial diagnosis. We found that ctDNA detection rates decreased at the first blood draw as compared to baseline (43% to 7% of patients). Total ctDNA abundance decreased in 6 patients and increased in 5 patients between those same blood draws, with one patient showing evidence of tumoral heterogeneity. Both patients with stage II/III disease had the largest increases in ctDNA abundance from baseline. Multiple blood draws improved ctDNA detection rates from 43% to 50% with a second blood draw and to 71% with 4 blood draws. Additionally, EGFR mutations were detectable in 6 patients during EBRT that were not detected prior to treatment. Taken together, these results provide an early-stage NSCLC counterpoint to previous work that reported improved ctDNA detection after radiation therapy in more advanced disease.

Simple Summary The role of neoadjuvant therapy in pancreatic cancer is poorly defined. Our results show improved overall survival in patients who received neoadjuvant therapy, driven by improved chemotherapy delivery, with no apparent increase in early or late perioperative complications. The role of neoadjuvant chemoradiotherapy and/or chemotherapy (neoCHT) in patients with pancreatic ductal adenocarcinoma (PDAC) is poorly defined. We hypothesized that patients who underwent neoadjuvant therapy (NAT) would have improved systemic therapy delivery, as well as comparable perioperative complications, compared to patients undergoing upfront resection. This is an IRB-approved retrospective study of potentially resectable PDAC patients treated within an academic quaternary referral center between 2011 and 2018. Data were abstracted from the electronic medical record using an institutional cancer registry and the National Surgical Quality Improvement Program. Three hundred and fourteen patients were eligible for analysis and eighty-one patients received NAT. The median overall survival (OS) was significantly improved in patients who received NAT (28.6 vs. 20.1 months, p = 0.014). Patients receiving neoCHT had an overall increased mean duration of systemic therapy (p < 0.001), and the median OS improved with each month of chemotherapy delivered (HR = 0.81 per month CHT, 95% CI (0.76-0.86), p < 0.001). NAT was not associated with increases in early severe post-operative complications (p = 0.47), late leaks (p = 0.23), or 30-90 day readmissions (p = 0.084). Our results show improved OS in patients who received NAT, driven largely by improved chemotherapy delivery, without an apparent increase in early or late perioperative complications compared to patients undergoing upfront resection.

PURPOSE:We describe the implementation of a novel virtual educational program for medical students, Radiation Oncology Virtual Education Rotation (ROVER), and its effect on student interest and knowledge in radiation oncology.METHODS AND MATERIALS:ROVER comprised a series of virtual educational panels with case-based discussions across disease sites tailored to medical students. The panels were moderated by radiation oncology residents and included faculty panelists from academic radiation oncology programs across the country. Student pre- and postsession surveys were collected. Paired t tests were used to compare the pre- and postsession assessment results.RESULTS:Six ROVER sessions were held from June 4, 2020, to August 20, 2020, with a total of 427 medical students registering for at least 1 session. Of these, 231 students attended at least 1 session, with 140 completing at least 1 postsession survey (60.6% response rate). Fourth-year medical students were the largest group represented among attendees (32.0%). Most attendees had exposure to radiation oncology (78.8%) before the sessions. The majority of students signed up for these sessions for education (90.6%). Some students signed up for the sessions to help with specialty selection (30.9%) and to network (30.4%). Medical students' understanding of the role of radiation oncology in each disease site (breast, sarcoma, central nervous system, pediatrics, gastrointestinal, genitourinary, gynecologic, lymphoma, lung, and head and neck) was improved by attending each session (pre- vs postsession; P < .0001 for all disease sites). Over three-quarters of respondents stated they were considering applying or were likely to apply to radiation oncology both before and after the sessions.CONCLUSIONS:ROVER improved medical student perceived knowledge of radiation oncology across all disease sites covered. ROVER fulfills a need for a national medical student education platform for radiation oncology. Future work is warranted to augment virtual and open educational platforms to improve access to radiation oncology education.

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n = 3) and rectal cancer (n = 2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the Dual-Index Degenerate Adaptor-Sequencing (DIDA-Seq) error-correction method, we serially interrogated plasma cell-free DNA at 28–41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient- and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted.

BACKGROUND Determination of the comparative efficacy of one therapy over another for hepatocellular carcinoma (HCC) can be challenging. Application of a recognized value framework to published studies could objectively compare the potential benefit across available therapies. MATERIALS AND METHODS An umbrella review of phase III trials for HCC therapies was performed. ASCO Value Framework Net Health Benefit Score version 2 (ASCO-NHB v2) scores, the primary analysis, and European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 scores, the secondary analysis, were computed using selected drug registration trials. Both scores were compared between drugs that were Food and Drug Administration (FDA)-approved by 2020 and those that were not. RESULTS Of the 22 studies identified, nine were FDA-approved and 13 were not. Across 22 trials, the median overall survival (OS) was 9.2 months (range, 1.9-16.4 months), with a median gain of 0.35 month (range, 2.3-3.3 months). HCC therapies that were FDA-approved showed longer OS (median 10.7 v 7.9 months, P < .01) and higher ASCO NHB scores (+18.4 v -5.7 scores, P < .01). The median gain in OS was 2.2 months in the approved treatments compared with -0.3 months in the unapproved group, with no difference in progression-free survival between the two groups. CONCLUSION The nine FDA-approved therapies for HCC have higher mean NHB score than those that were not FDA-approved. The application of ASCO-NHB v2 and other proposed value frameworks could examine data of future therapies for HCC through a patient-oriented approach.