6061 Background: In several cancers, including head and neck squamous cell carcinoma (HNSCC), the immunosuppressive components of the tumor microenvironment (TME) can impact the effectiveness of immune checkpoint inhibitors (ICI). One significant component of the TME is the extracellular matrix, which is rich in collagen fibers. In this work we used machine learning and image analysis approaches on whole slide images (WSIs) to characterize collagen disorder architecture (CoDA) features and evaluated their association with outcomes in HNSCC patients receiving ICI. Methods: WSIs of HNSCC patients treated with ICI were obtained from University Hospitals (S1, n=43) and Emory University (S2, n=31). Tiles from the tumor annotated regions of the WSIs were extracted, and a derivative-of-Gaussian model was used to identify collagen fibers in the stroma of these tiles. Various CoDA features were then calculated as follows: (1) collagen fiber fragmentation measure, (2) collagen fiber bundling percentage, (3) collagen fiber rigidity measure, (4) collagen fiber anisotropy index and (5) collagen fiber density index. CoDA features of S1and S2 were combined and split into 50:50 for training and validation. For survival analysis using overall survival (OS) as endpoint, the median risk score in the training set was applied for risk stratification in the validation set by means of a Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression model. For predictive analysis, CoDA features from patients with objective response (OR) to ICI were identified (S1, non-responder=23, responder=20), (S2, non-responder=23, responder=8). The top features were then selected using the LASSO and combined with a Generalized Linear Model classifier. A 5-fold cross-validation assessed Area Under the Receiver Operating Characteristics Curve (AUC) for predicting OR, with average AUC as the final performance metric in the validation set. Results: For survival analysis, high risk patients in the validation set had worse survival than low risk patients (HR=2.7 (95% CI=1.1-6.6, p=0.02)). For predicting OR, the selected top CoDA features were collagen fiber fragmentation measure, collagen fiber bundling percentage, collagen fiber rigidity measure and collagen fiber density index and the average AUC was 0.64±0.16. More fragmentation of the collagen fibers along with dense thick bundles and straightened fibers were observed in the WSIs of non-responder patients to ICI. Conclusions: High risk CoDA features correlated with worse survival in patients with HNSCC receiving ICI. Also, we established a correlation of specific CoDA features with OR to ICI. The prognostic and predictive value of CoDA deserves additional exploration with confirmatory data from larger, independent multi-site validation.

e14710 Background: Lung cancer affects a disproportional number of socioeconomically disadvantaged patients (pts). Responses to checkpoint inhibitor therapy (CIT) vary. Microbiome diversity may correlate with benefit from CIT. High fiber diets lead to microbiome diversity. We hypothesize that unexplained lung cancer disparities may be in part due to differences in microbiome diversity determined by unhealthy dietary patterns dictated by lower SES. Methods: Following IRB review, 25 pts with metastatic NSCLC starting CIT-based treatment were enrolled. Pre-treatment oral and fecal samples were collected. 24-hour dietary recalls were obtained. SES index was calculated based on education, employment, housing and annual income. High fiber intake was defined as > 20 g/day. Best treatment response per RECIST 1.1 was assessed. Microbial 16s rRNA were sequenced with Illumina MiSeq platform. Sequence analyses utilized QIIME 2 with DADA2 plugin. Taxonomic assignments used the Greengenes database. Microbiome composition was analyzed by calculating alpha diversity (Chao1, Shannon diversity and Simpson index), beta diversity and differential abundance of microbial compositions. Hierarchical linear model was constructed for each SES variable with and without biological covariates. Results: Pts with samples >1000 operational taxonomic unit (OTU) levels were included (N = 22) in the analysis. 50% were male, median age was 71, 36% (8/22) were of Black race and 23% (5/22) were of low SES. Median fiber intake was 11.9 grams. Males had higher alpha diversity than females (p=.038). Pts with high fiber intake had greater fecal Proteobacteria compared to low fiber intake pts (p<0.05). Bacteroides and Firmicutes fecal levels were significantly different for all pts compared to Human Microbiome Project (HMP) reported normal levels (p<0.01). Actinobacteria and Proteobacteria levels for low-fiber intake pts were also significantly elevated compared to HMP normal levels (p<0.05). There were no differences observed in microbiome when comparing SES index. However, high SES index patients had elevated fecal levels of Actinobacteria, Firmicutes and Proteobacteria and lower levels of Bacteroides compared to HMP levels. There was a trend towards higher alpha diversity of oral samples in partial responders pts compared to those with stable or progression of the disease (p=0.08). Conclusions: Pts with metastatic NSCLC exhibited different microbial composition compared to HMP normal levels. Associations between SES and microbial distribution in such pts warrant further investigation. Increased sample size is needed to better determine differences in oral microbiome in responders to immunotherapy and better evaluate the role of sex in this setting.

PURPOSECancerLinQ seeks to use data sharing technology to improve quality of care, improve health outcomes, and advance evidence-based research. Understanding the experiences and concerns of patients is vital to ensure its trustworthiness and success.METHODSIn a survey of 1,200 patients receiving care in four CancerLinQ-participating practices, we evaluated awareness and attitudes regarding participation in data sharing.RESULTSOf 684 surveys received (response rate 57%), 678 confirmed cancer diagnosis and constituted the analytic sample; 54% were female, and 70% were 60 years and older; 84% were White. Half (52%) were aware of the existence of nationwide databases focused on patients with cancer before the survey. A minority (27%) indicated that their doctors or staff had informed them about such databases, 61% of whom indicated that doctors or staff had explained how to opt out of data sharing. Members of racial/ethnic minority groups were less likely to be comfortable with research (88% v 95%; P = .002) or quality improvement uses (91% v 95%; P = .03) of shared data. Most respondents desired to know how their health information was used (70%), especially those of minority race/ethnicity (78% v 67% of non-Hispanic White respondents; P = .01). Under half (45%) felt that electronic health information was sufficiently protected by current law, and most (74%) favored an official body for data governance and oversight with representation of patients (72%) and physicians (94%). Minority race/ethnicity was associated with increased concern about data sharing (odds ratio [OR], 2.92; P < .001). Women were less concerned about data sharing than men (OR, 0.61; P = .001), and higher trust in oncologist was negatively associated with concern (OR, 0.75; P = .03).CONCLUSIONEngaging patients and respecting their perspectives is essential as systems like CancerLinQ evolve.

6047 Background: Though immunotherapy (IO) has robust clinical efficacy, only a subset of head and neck squamous cell carcinoma (HNSCC) patients have shown to benefit from it. Collagen, a major component of the Tumor Microenvironment (TME), is involved in cancer fibrosis and collagen fiber organization has been shown to be associated with patient outcome for different cancers. In this work, we evaluated whether computationally extracted collagen fiber orientation disorder (CFOD) features from tumor related stroma regions (TS) in digitized H&E-stained slides can help in distinguishing between responders and non-responders to immunotherapy in HNSCC patients. Methods: Whole slide images (WSIs) from 43 HNSCC patients treated with immunotherapy (23 non-responders and 20 responders) were obtained from University Hospitals, Cleveland; response was defined as per RECIST v1.1. A derivative-of-Gaussian model was used to identify collagen fiber orientations in TS of the digitized WSIs. Different statistics (e.g. mean, standard deviation, skewness) of the various disorder descriptors (e.g., contrast and entropy) were calculated across all the neighborhood windows in the tumor region to generate the final CFOD feature set. Minimum Redundance Maximum Relevance algorithm was employed to identify the top 3 features, which were combined with a Naive Bayes classifier to differentiate between responders and non-responders. Cross-validation was used to validate the classifier over 100 iterations via the area under the receiver operating characteristics curve (AUC). Multivariable analysis was done using a logistic regression method to see how different parameters (gender, age, smoking status) will affect IO response. Results: WSIs of responders to immunotherapy showed more disorganized collagen fiber structure as compared to non-responders WSIs. The selected top 3 features were related to the contrast feature descriptor from the orientation co-occurrence matrix. The average AUC for the model based on CFOD was 0.77±0.24. The results for multivariable analysis are shown in Table 1. Conclusions: We demonstrated an association between the architectural organization of collagen fiber from baseline biopsies of HNSCC patients with response to immunotherapy. Furthermore, we demonstrate a classifier based on computationally derived CFOD features able to derive detailed assessments of collagen orientation. None of the parameters analyzed were significantly associated with change in IO response (p<0.05). Further validation on a larger independent cohort is warranted. Multivariable analysis for IO response. Parameter p value Gender (Male/Female) p=0.14 Age (<60 years/≥60years) p=0.19 Smoking status (Yes/No) p=0.54

Abstract Purpose: TRC102, a small-molecule base-excision repair inhibitor, potentiates the cytotoxicity of pemetrexed and reverses resistance by binding to chemotherapy-induced abasic sites in DNA. We conducted a phase I clinical trial combining pemetrexed and TRC102 with cisplatin–radiation in stage III nonsquamous non–small cell lung cancer (NS-NSCLC). Patients and Methods: Fifteen patients were enrolled from 2015 to 2019. The primary objective was to determine the dose-limiting toxicity and maximum tolerated dose of TRC102 in combination with pemetrexed, cisplatin, and radiotherapy. Secondary objectives were to assess toxicity, tumor response, and progression-free survival at 6 months. Based on our preclinical experiments, pemetrexed–TRC102 was given on day 1, and cisplatin/radiotherapy was initiated on day 3. This schedule was duplicated in the second cycle. After completion, two additional cycles of pemetrexed–cisplatin were given. Toxicities were assessed using NCI CTACAE versions 4/5. Results: The median age was 69 years (45–79) with the median follow-up of 25.7 months (range, 7.9–47.4). No dose-limiting toxicities and no grade 5 toxicity were seen. Hematologic and gastrointestinal toxicities were the most common side effects. No clinical radiation pneumonitis was seen. Of 15 evaluable patients, three had complete response (20%), and 12 had partial response (80%). The 6-month progression-free survival was 80%, and the 2-year overall survival was 83%. Conclusions: Pemetrexed–TRC102 combined with cisplatin/radiotherapy in NS-NSCLC is safe and well tolerated. The recommended phase II dose is 200 mg TRC102 along with cisplatin–pemetrexed. No additional safety signal was seen beyond the expected CRT risks. A phase II trial, integrating post-CRT immunotherapy with this aggressive DNA-damaging regimen, is warranted.

PURPOSE:Comprehensive tumor biomarker testing is a fundamental step in the selection of highly effective molecularly driven therapies for a variety of solid tumors. The primary objective of this study was to examine racial differences in biomarker testing and clinical trial participation in the United States using a real-world database.METHODS:Patients in a real-world deidentified database diagnosed with advanced/metastatic non-small-cell lung cancer (NSCLC), metastatic colorectal cancer (CRC), or metastatic breast cancer were eligible. Biomarker testing and clinical trial participation was compared between Black and White racial groups using chi-squared test and stepwise logistic regression controlling for baseline covariates.RESULTS:A total of 23,488 patients met eligibility criteria. Next-generation sequencing (NGS) testing rates differed significantly between White versus Black race before first-line therapy (36.6% v 29.7%, P < .0001) and at any given time (54.7% v 43.8%, P < .0001) in the nonsquamous NSCLC cohort. Similar disparities in NGS testing rates at any time during the study were observed among patients with CRC (White 51.6%; Black 41.8%, P < .0001). No differences were observed in the breast cancer cohort. Patients of Black race were less likely to be treated in a clinical trial in the overall NSCLC cohort when compared with White counterparts (3.9% v 2.1%, P = .0002). A statistically significant relationship between biomarker/NGS testing and clinical trial enrollment was observed in all cohorts (P < .003) after adjusting for covariates.CONCLUSION:In a real-world database, significant disparities in NGS-based testing rates were observed between Black and White races in NSCLC and CRC. NGS and any biomarker testing were both associated with trial enrollment in all cohorts. There is a need for interventions to promote access to comprehensive testing for patients with advanced/metastatic tumors.

Purpose: Patients with head and neck (H & N) and esophageal cancer are at high risk for treatment-related symptomatic dehydration, often leading to interventions and hospital admissions. We tested the hypothesis that preemptive daily oral hydration during curative-intent radiation therapy would decrease dehydration as measured by intravenous fluid (IVF) delivery, acute care clinic (ACC) visits, and emergency department (ED) presentations. Methods and Materials: Patients with H & N or esophageal cancer undergoing definitive radiation therapy were enrolled in this prospective pilot study. Beyond standard nutritional counseling, patients were given one 20-oz bottle of an electrolyte-infused solution (EIS) daily throughout treatment. Compliance, presentations to the hospital ACC and/or ED for dehydration-related indications, and IVF infusions were documented and compared with a matched contemporary control cohort. The incidence and frequency of outcomes were compared with the Fisher exact test and Wilcoxon rank-sum test, respectively. Results: Thirty-one patients were compared during a 6-month period. Mean and median compliance rates were 87.4% and 100%, respectively. There were 0 unplanned dehydration-related ED presentations in the study group versus 3 (9.7%) among controls (P = .08). Of patients in the intervention cohort, 32.3% required presentation to the ACC, versus 64.5% in the control cohort (P = .02), with a total of 26 versus 117 visits, respectively (P = .002). On multivariable analysis, receipt of the EIS in the intervention cohort was the only significantly associated factor (P = .02). Among patients in the intervention cohort, 35.5% required IVF during treatment, versus 64.5% among controls (P = .004). The difference in ACC visits (P = .003) and IVF received (P = .008) was especially notable among patients with esophageal cancer. Patients with & GE;60% EIS compliance had slightly fewer ACC visits versus those with < 60% compliance (P = .067). Conclusions: Regimented oral hydration during radiation for H & N and esophageal cancer was associated with a significant decrease in ACC visits and IVF delivery during definitive radiation therapy. This noninvasive and inexpensive preventative program in a high-risk cohort warrants further study. (C) 2022 The Author(s). Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.

OPINION STATEMENT:Advanced non-melanoma skin cancers have been challenging to treat due to limited treatment options. Treatment paradigm has shifted with the approval of immunotherapeutic agents cemiplimab and pembrolizumab which have been a key development and have changed the landscape of advanced or metastatic squamous cell skin cancers. Hedgehog inhibitors, vismodegib and sonidegib, remain upfront options for advanced or metastatic basal cell carcinomas. Current clinical trials are continuing to evaluate the use of immune checkpoint inhibitors and hedgehog pathway inhibitors. There is further need for ongoing research and development of new therapies in both malignancies.

9005 Background: Cancer racial disparities may exist at many levels in the health care system, from screening to timely diagnosis and treatments received, as well as clinical trial enrollment. This study investigated differences in black versus white race among patients with NSCLC undergoing biomarker testing and clinical trial enrollment in the US. Methods: This retrospective observational study utilized the Flatiron Health database, which includes longitudinal data of patients with advanced/metastatic NSCLC. Patients were eligible if they had evidence of systemic therapy in the database from 1/1/2017 through 10/30/2020. Descriptive analyses summarized differences by race in biomarker testing and trial enrollment. Multivariable regression examined the relationship between these factors. Results: A total of 14,768 patients were eligible: 9,793 (66.3%) were white and 1,288 (8.7%) were black. 76.4% of white patients and 73.6% of black patients underwent at least one single molecular test or comprehensive genomic analysis (p = 0.03). Next-generation sequencing (NGS) was performed among 50.1% of white patients and 39.8% of black patients (p < 0.0001. Trial participation was observed among 3.9% of white and 1.9% of black patients (p = 0.0002). There was a statistically significant association between race (white vs black) and both biomarker testing (ever vs never) and trial participation (yes vs no) (both p < 0.001, unadjusted chi square). Differences in NGS testing, baseline biomarker testing, and race were retained as statistically significant (p < 0.01) in adjusted regression analyses. The receipt of first-line targeted therapy was comparable between white and black patients (10.2% and 9.2%, respectively, p = 0.24); however, this summary did not consider biomarker test results. First line use of pembrolizumab+carboplatin+pemetrexed was observed among 19.8% of white and 22.6% of black patients; carboplatin+paclitaxel was observed among 16.5% and 18.6%, and single-agent pembrolizumab was observed among 14.8% and 11.5%, respectively. Conclusions: The use of NGS-based testing, which is recommended by the National Comprehensive Cancer Network Clinical Guidelines in Oncology for patients with advanced/metastatic NSCLC, is the most notable disparity among black patients, with more than a 10 percentage-point difference in receipt of this testing versus white counterparts. This may in part contribute to the more than double the rate of participation in clinical trials observed among white patients, as many second line and beyond trials utilize molecular targets as inclusion criteria. While multiple factors are known to impact health care disparities, access to and receipt of appropriate biomarker testing may be an attenable goal in order to ensure equal access to quality care.

In head and neck squamous cell carcinoma (HNSCC), anti-PD-1 inhibitors are approved for recurrent/metastatic (R/M) disease and anticipated to expand to other indications. The impact of p16 status and anatomical site on overall survival (OS) in immunotherapy-treated HNSCC patients remains unresolved. We performed a retrospective analysis of R/M HNSCC patients receiving anti-PD-1 immunotherapy at our academic medical center with an extensive community satellite network. Fifty-three R/M HNSCC patients were treated with anti-PD-1 immunotherapy and had a median OS of 6 months. Anatomical site was associated with distinct OS; oropharynx and larynx patients have superior OS compared to oral cavity patients. Analysis of the OPSCC subset showed p16+ status as a favorable, independent prognostic biomarker (HR 7.67 (1.23–47.8); p = 0.029). Further studies to assess the link between anatomical site, p16 status, and anti-PD-1 treatment outcomes in large cohorts of R/M HNSCC patients managed in real-world clinical practices and clinical trials should be prioritized.

125 Background: Racial disparities may exist at many levels in the health care system; in oncology, yet little is known about racial disparities in biomarker testing and clinical trial enrollment among patients with mCRC. This study was designed to explore racial differences in comprehensive biomarker testing and clinical trial enrollment in the US using a large real-world database. Methods: This retrospective observational study utilized the Flatiron Health electronic health records database, which includes longitudinal data from patients diagnosed with mCRC. Patients with mCRC were eligible for this study if they had evidence of systemic therapy from 1/1/2017 through 10/30/2020 and were alive for at least 120 days after metastatic diagnosis. Unadjusted analyses summarized differences in biomarker testing and clinical trial enrollment between White and Black race, adjusted regression analyses were conducted using all baseline variables as covariates. These data are de-identified and are not considered human subjects research in accordance with the US Code of Federal Regulations (45 CFR Part 46). Results: A total of 7,879 patients were eligible: 4,803 (61.0%) were White and 838 (10.6%) were Black. Comprehensive testing by next-generation sequencing (NGS) was received by 51.6% and 41.8% of patients who were White and Black, respectively (p < 0.0001). There was no significant difference in clinical trial participation across all lines of therapy (2.9%, White and 2.9% Black). There was a statistically significant relationship between NGS-based testing and clinical trial enrollment (p < 0.0001), however, race was not identified a moderating factor in this relationship in adjusted regression analyses. The receipt of molecularly-targeted therapy was comparable between both races (11.9% and 9.7% for White and Black, respectively; p = 0.06). Patients received FOLFOX+bevacizumab most commonly in the first line (34.3% White; 40.5% Black), all other regimens were within 2 percentage points between racial groups. Targeted agents were each used by less than 7.4% of the study population. Conclusions: The use of NGS-based testing is significantly different by race in this database. The significant relationship between NGS testing and clinical trial enrollment at any time in the database did not appear to be moderated by race; however, descriptive analyses suggest that the ongoing analyses by line of therapy and considering timing of testing may better quantify these relationships. These data may not be generalizable to the entire US population as they are obtained from a single database that is limited to practices using this EHR system.

e18516 Background: Lack of diverse representation in clinical trials negatively impacts the cancer survival of patients and populations unaccounted for in clinical research. Efforts such as the 1993 NIH Revitalization Act have focused on improving the diversity of trial participants in the US. This retrospective study evaluated the racial distribution of oncology clinical trial participants using data published in clinicaltrials.gov from Jan 2010 through Dec 2020. Methods: I2E of Linguamatics (IQVIA, Inc), a natural language processing software, was used to identify participant race in oncology trials. Data extracted included trial identifier, year of completion, sponsor, cancer type, and race. Studies were limited to academic, cooperative group and government studies headquartered in the US. Clinical trial results were compared to the racial distribution of SEER 2010 data using z-test. Results: Data from 35,686 patients (14,220 enrolled to 236 phase 2 and 21,471 enrolled to 47 phase 3 trials) were available for analysis. A summary by race is provided in the Table, excluding unknown, which represented 8.5% of phase 2 and 3.5% of phase 3 trials. The proportions of white/black patients enrolled to phase 2 and phase 3 trials beginning in 2010-12 were 84.4%/11% and 83.1%/9.9%, respectively (total enrollment 84.9%/9.6%). For trials beginning in 2015-17, white/black enrollment represented 88.5%/8.1% of patients enrolled to phase 2 and 86.4%/10.1% of patients in phase 3 trials. Black patients represented 9.6% of all trial participants, in contrast with the SEER data where 12% of all patients were black (p < 0.001). For lung cancer trials, black participants represented only 7.9% of all trial participants whereas in breast cancer trials, 10.2% of participants were black, versus the SEER data specific to these tumor types (black patients represent 10.9%/11.5% of lung/breast cancer diagnoses between 2013 to 2017, both p < 0.01). Conclusions: This study suggests that over the past decade most races (other than white) have been significantly underrepresented in US oncology clinical trials, and is even more pronounced for black patients with lung cancer. Based on this analysis, there is no evidence that trial enrollment distribution, particularly of white versus black participants, has changed since 2010. Data are limited to the relative lack of studies reporting results that began enrollment after 2017. These findings suggest that the development of new strategies to improve the recruitment of racial minorities to oncology clinical trials are warranted.[Table: see text]

Anti-PD-1 immunotherapies (IOs) have robust clinical benefit in a subset of head and neck squamous cell carcinoma (HNSCC) patients and is considered as a standard of care option in the recurrent/metastatic setting.1 Previous studies showed association of higher number of lymphocytes and density of tumor-infiltrating lymphocytes (TILs) with better survival probability and prognosis in HNSCC patients.2 3 In this study, we evaluate whether the spatial interplay between TILs with surrounding nuclei and TIL density from digitized H&E-stained slides was associated with better immunotherapy response in HNSCC patients.Whole slide images (WSIs) from 43 HNSCC patients treated with IO at University Hospitals, Cleveland were selected. Response to immunotherapy was defined as per RECIST v1.1.4 Computerized algorithms identified and built clusters for nuclei of TILs and TIL density and spatial arrangement of the clusters was quantified using network graph-metrics. To assess the predictive ability of the combination of spatial arrangement and density features of TILs, a cross-validation scheme was used as follows: at each iteration, the dataset was randomly split into training (60%) and validation sets (40%). The Wilcoxon method selected top two features in the training set, then used to train a Naïve Bayes classifier to differentiate between responders and non-responders. Next, the classifier was applied to the validation set and its performance was evaluated by computing the area under the curve (AUC) for the receiver operating characteristic (ROC) curve. This process was repeated 250 times. For comparison, the same cross-validation procedure was used on (1) TIL arrangement and (2) TIL density features.Figure 1(A) and 1(B) show the violin plots corresponding to the two selected top features across the cross-validation iterations for responders and non-responders. Figure 1(C) illustrates the average ROC curves for the three assessed models and corresponding AUC. The average AUCs for the model based on combination (TIL arrangement + TIL density), TIL arrangement and TIL density only yielded an average AUCs of 0.84+0.14, 0.81+0.02 and 0.74+0.06 respectively. After DeLong assessment of the ROC curves, significant difference was found for TIL combination vs. TIL density (p=0.03) whereas no significant difference was found for TIL combination vs. TIL arrangement (p=0.55).We present a predictive model based on image biomarkers i.e. spatial interplay between TILs and surrounding nuclei along with TIL density in order to distinguish HNSCC patients responding and not responding to immunotherapy. The model based on TIL combination performed better in comparison to only TIL density.Patel RR, Ludmir EB, Augustyn A, et al. De-intensification of therapy in human papillomavirus associated oropharyngeal cancer: a systematic review of prospective trials. Oral Oncol 2020;103:104608. https://doi.org/10.1016/j.oraloncology.2020.104608.Lilja-Fischer JK, Eriksen JG, Georgsen JB, et al. Prognostic impact of PD-L1 in oropharyngeal cancer after primary curative radiotherapy and relation to HPV and tobacco smoking. Acta Oncol 2020;59(6):666–672. https://doi.org/10.1080/0284186X.2020.1729407.Peled M, Onn A, Herbst RS. Tumor-infiltrating lymphocytes—location for prognostic evaluation. Clin Cancer Res 2019;25(5):1449–1451. https://doi.org/10.1158/1078-0432.CCR-18-3803.Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000;92(3):205–16. https://doi.org/10.1093/jnci/92.3.205Abstract 829 Figure 1(A) Violin plot for topmost feature 1 selected by Wilcoxon test (Feature selected from number of clusters surrounding a specific cluster type) (Responder vs. Non-responder p=0.0006). (B) Violin plot for topmost feature 2 selected by Wilcoxon test (Feature selected from the intersected area from the cell clusters formed from the centroids of the cell clusters) (Responder vs. Non-responder p=0.00016) (C) Average receiver operating characteristic curves for the 3 assessed models i.e. TIL combination (AUC=0.84+0.14), TIL arrangement (AUC=0.81+0.02) and TIL density (AUC=0.74+0.06). Significant difference between the ROC curves i.e. TIL combination vs. TIL density (p=0.03), TIL combination vs. TIL arrangement (p=0.55), TIL arrangement vs. TIL density (p=0.32)

212 Background: Prior authorizations in medical oncology generate additional work and subsequent stress to providers, contributing to physician burnout. Denials of payments can also impact patient care and lead to loss of revenue for the institution. In 2018, first pass denial rates averaged 8.41% per month at our institution. Imaging/scans denials created the majority of this additional work for providers. We aimed to decrease the monthly first pass denial rate average of oncology scans by 25% by May 31, 2020. Methods: Following the creation of a process map of the current prior authorization process and a cause and effect diagram, we identified many factors that could not be controlled (i.e. Insurance company policies). We subsequently created a priority/pay-off-matrix using factors that we could control. Introducing standardized order template for oncology scans was identified as a high impact and feasible countermeasure. Plan-do-study-act cycles (PDSA) plan was developed using this countermeasure to achieve our aim. PDSA 1 included creating template for order entry, educating the nurse partners and advance practice providers (APPs). PDSA 2 included educating physicians and measuring the compliance rate of the template. PDSA 3 addressed the barriers for compliance and education on resources was provided. PDSA 4 included education of the prior authorization staff and reinforcement of template use. A sustainability plan created consisting of a designated RN liaison for review of peer-to-peer requests for oncology scans. Results: PDSA 1: 100% of the nurse partners and APPs were educated. PDSA2: 80% of physicians were educated and 32.8% compliance rate of template use. PDSA 3: 39.2% compliance. PDSA 4: 95% of the radiology prior authorization staff was educated. While our compliance rate for the standardized order template use did increase, we identified many other opportunities to improve the process. Unfortunately, due to COVID-19 pandemic outbreak, resources have been temporarily allocated to relief efforts and the sustainability plan continues to be a work in progress. Conclusions: Peer to peer requests for imaging/scans following authorization denials consume time and effort of providers contributing to burnout and potentially impacting patient care. While many factors cannot be controlled, standardizing ordering process and educating the involved personnel may decrease the number for peer to peer requests. ASCO’s quality training program process helped our institution identify a provider controlled barrier and helped standardize this approach.

e14103 Background: The rapid development of digital technology holds enormous potential to transform the delivery of cancer care. Despite these digital innovations, we still face significant challenges in healthcare in using these emerging digital technologies in the clinical setting. Clinicians generally underestimate the severity and extent of chemotherapy toxicity of patients. This project seeks to conduct an exploratory field study to collect patient feedback on their experiences, and the design/functionality of the prototype of the digital health service platform designed to monitor their symptoms. Methods: Using the National Cancer Institute item library addressing the most common symptoms for chemotherapy toxicity, a digital health platform was designed by Samsung Research America (SRA) and University Hospitals. Patients age ≥ 18 years old, willingness to agree to the consent document, ability to understand use of wearable device and willingness to answer patient reported outcomes questions were included in this study. Patients who are not undergoing oral chemotherapy treatment for their cancer were excluded. Patients were given a phone that had our designed platform along with a watch. The watch had the capability of tracking blood pressure, heart rate, and pulse oximetry. Patients were set up with an electronic account that queried them on patient Reported Outcomes (PRO) regarding potential toxicity they may be experiencing. They were also able to track medication consumption and input their weight. Subjects were be asked to use the wearable device and phone for at least 28 days and no more than 90 days. At the end of the study, a phone survey was attempted. Results: Total patients enrolled: 21. 18/21 (85.7%) patients completed the 90 days of the study. Only 9 patients provided PRO with total number of side effects reported 28 times. Watch device was only utilized by 15/21 (71.4%) patients. On an average across 90 days, these patients wore the watch 430 minutes per day. At the end of the treatment, 5 patients agreed to participate in the phone survey. Three patients stated that they would do similar study in the future noting that the digital platform helped them stay on track and monitor symptoms accurately. Every patient questioned had a complaint regarding the watch functionality. Patients also found it difficult to carry a second phone in addition to their personal phone. Conclusions: Improving our digital health service platform will get us closer to achieving effective bi-lateral patient communication and ultimately improving patient care.

9027 Background: About 35% of all NSCLC presents with locally advanced disease and chemo-radiation results in 5-year OS of only ~31%. PEM-platinum combination is approved in stage IV NSCLC and has similar efficacy to platinum-etoposide in stage 3 NSCLC and a favorable toxicity profile (Proclaim trial). TRC102 is an oral small molecule inhibitor of BER. TRC102 potentiates the cytotoxicity of antimetabolites and alkylators and reverses chemotherapy resistance by rapidly and covalently binding to chemotherapy-induced abasic sites in DNA. TRC102 increased radio-sensitization by PEM of NSCLC cell lines and H1299 and A549 xenografts. Methods: Between 11/2015 and 5/2019, 15 patients were enrolled in a 3+ 3 design: 12 with stage III and 3 with oligometastatic stage IV NS-NSCLC. The primary objective was to determine dose-limiting toxicities (DLT’s) and recommended Phase 2 dose (RP2D) of TRC102 in combination with PEM, cisplatin and radiotherapy. Secondary objectives were to assess toxicity, tumor response and PFS at 6 months. Based on pre-clinical data, PEM-TRC102 was given on day 1, and cisplatin/radiotherapy was initiated on day 3. This schedule was duplicated on day 21 and day 23 of the second cycle. After completion of radiotherapy, two additional cycles of PEM-cisplatin were given. Toxicities were assessed by NCI CTACAE version 4 and 5. Results: Median patient age was 69 years (45-79) and median follow up was 16.6 months (3.1-38.6). There were no DLTs or grade 5 toxicity. Hematologic and GI toxicities were the most common adverse events (Table) and radiation pneumonitis was not seen. The RP2D of TRC102 was 200 mg when given with cisplatin/radiotherapy and PEM. Of 15 evaluable patients, 3 had CR (20%) and 12 had PR (80%). The 2-year PFS rate was 49%. Conclusions: PEM-TRC102 combined with cisplatin/radiotherapy in non-squamous NSCLC was safe and well tolerated, and did not cause safety signals beyond those expected from CRT. Preliminary response data and PFS in this cohort was encouraging. A phase 2 trial, integrating post-CRT immunotherapy with this aggressive DNA-damaging regimen is warranted. Clinical trial information: NCT02535325. [Table: see text]

37 Background: Immune related thyroiditis is a common adverse effect of Immune checkpoint inhibitors (ICI). We sought to determine if the incidence of hypothyroidism (HT) in patients with primary head and neck cancers (pHNC) who received ICI, is increased compared to other primary cancers (lung, gastrointestinal (GI), skin melanoma or urinary system(GU). Methods: Data were obtained from a commercial de-identified database (IBM Explorys Solutions, IBM, Inc.). Cases included patients ≥ 18 years with a diagnosis of pHNC and controls included patients with a diagnosis of lung, GI, skin melanoma or GU cancer. All patients received one of 5 ICI (Avelumab, Atezolizumab, Durvalumab, Nivolumab or Pembrolizumab). Incidence of HT was defined as patient with a new diagnosis of HT at least 1 day following initiation of ICI. All patients with diagnosed HT, thyroid cancer (previous/concurrent), lymphomas were excluded. Odds ratios (OR) and confidence intervals (CI) were calculated using chi-square test. Results: There were 238,490 patients with a diagnosis of pHNC, and 616,850 patients with a diagnosis of other cancers in the database. Out of 710 pHNC patients, 80 patients (18.6%) and out of 7420 patients with other primary cancers, 850 (12.57%) had a new diagnosis of HT. When compared to non-HNC patients, HNC cases had a 1.6 (CI = 1.23 - 2.05) times higher odds of developing HT. In subgroup analyses, HNC cases were significantly more likely to develop HT compared to patients with GI or lung cancer, but not with skin melanomas or GU cancers. Overall, male cases and adults aged 18 - 65 years were significantly more likely to develop HT. (Table). Conclusions: The risk of developing HT after ICI is higher in patients with HNC compared to other primary cancers. Men and patients between the ages 18-65 years with pHNC were more likely to become HT. [Table: see text]

Introduction The treatment of stage III non-small cell lung cancer (NSCLC) remains challenging and associated with overall poor outcomes. Since seminal studies in the early 90s introduced concurrent chemo-radiotherapy as standard of care for treatment of this disease, no major advances have been introduced in this landscape. Both radiation dose escalation and neoadjuvant/adjuvant chemotherapy strategies were unsuccessful to improve the survival over standard of care radiation dose and chemotherapy schedule: five-year overall survival (OS) ranging from 15-20%. However, in 2017 the PACIFIC Trial demonstrated that the addition of consolidative immune checkpoint inhibitor durvalumab for 1 year led to superior progression-free survival (PFS) and 3-year overall survival with no significant increase in toxicity compared to placebo in patients who achieved disease control with concurrent chemo-RT. Areas covered This article reviews the treatment evolution of stage III NSCLC over the past decades, discusses current standard of care strategies, and highlights potential future directions for the management of this condition. Expert opinion Ongoing trials incorporating upfront checkpoint inhibitors with radiotherapy will answer whether adding checkpoint inhibitors to chemotherapy or substituting them for chemotherapy altogether will improve long-term outcome.