The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

PurposeFinancial hardship from cancer care is associated with poor patient outcomes. Economic disruption during the COVID-19 pandemic may have exacerbated patients’ financial concerns. We explore how social deprivation index (SDI), clinical, and treatment-related factors impacted financial hardship in this observational secondary analysis using data collected prospectively during implementation of financial hardship screening from our NCI-designated center during COVID-19.MethodsAdults aged ≥18 years undergoing active treatment for stage 0-IV breast or lung cancer and who completed a 5-point Likert response-item screening for financial difficulty between 11/2020 and 11/2021 were included. Generalized estimating equations assessed associations between quartiles of zip-code level SDI, a composite obtained using data from US Census and American Community Survey, and binary outcome of financial hardship adjusting for relevant covariates.ResultsOf 2245 patients, 87% identified as White, 9% as Black, 2% as Asian. The majority of patients identified as non-Hispanic (99%). Median age was 62 years old (IQR 53–71).The majority were treated for breast cancer (79%). Significant financial hardship (Likert responses ≥2) was reported by 7%. Most were married, had managed-care insurance, resided in urban settings, and had early-stage cancers (all p < 0.001). Of those included, 83% received surgery, 52% received chemotherapy, and 65% received radiation. Compared to the lowest SDI quartile, penultimate and highest quartiles were associated with financial hardship (Q3 aOR 1.86; 95%CI 1.13–3.05); Q4 aOR 2.05; 95%CI 1.15–3.63). Younger age, Black race, comorbidities, radiation, and chemotherapy were also associated with greater financial hardship (p < 0.05).ConclusionIn this study, greater SDI, younger age, Black race, comorbidities, receipt of radiation and/or chemotherapy were associated with financial hardship. These factors may guide focused screening of vulnerable populations to assist with equitable access to resources that offset the economic effects of cancer care.

TPS292 Background: Neuroendocrine differentiated prostate cancer (NED PCa) is an aggressive form of prostate cancer with few treatment options and a poor prognosis. There is evidence that NED PCa and advanced castration resistant prostate cancers (CRPC) overexpress the somatostatin receptor (SSTR), which can be targeted with Lu-177 DOTATATE, a radiopharmaceutical therapy that improves survival in neuroendocrine tumors of the midgut. We are conducting a phase II trials investigating Lu-177 DOTATATE in NED PCa. Methods: This is a phase II trial run through the National Cancer Institute’s (NCI) Experimental Therapeutics Clinical Trials Network (ETCTN). Key inclusion criteria include evidence of neuroendocrine differentiation by histology (i.e. small cell carcinoma or positivity for synaptophysin or chromogranin A), molecular features (TP53, PTEN, and/ or RB1 loss), serum markers (chromogranin A or neuron-specific enolase), or clinical factors (progression of visceral metastases in the absence of PSA progression). Patients must have a positive Ga-68 DOTATATE PET/CT to proceed with Lu-177 DOTATATE therapy, defined as at least 1 lesion with a maximum standardized uptake value (SUV max ) greater than the mean SUV of normal liver. The primary objective for the trial is objective response rate (ORR), defined by Prostate Cancer Working Group 3 (PCWG3) criteria. Secondary objectives include 6-month radiographic progression-free survival as well as the correlation between ORR and change in fluorodeoxyglucose PET/CT signal pre- to mid-treatment. Exploratory objectives include SPECT/CT-based dosimetry of Lu-177 DOTATATE and gene expression analysis of circulating tumor cells collected prior to treatment, during treatment, and at time of progression. A pre-specified activity goal for the first 15 enrolled patients was met, and accrual of an additional 10 patients is currently in progress. Clinical trial information: NCT05691465 .

PURPOSE National Comprehensive Cancer Network guidelines recommend weekly cisplatin and weekly carboplatin with paclitaxel as alternative concurrent systemic therapy regimens among patients with head and neck cancer undergoing definitive chemoradiation. However, there is a paucity of literature comparing outcomes with these two regimens. We performed an observational cohort study of patients with head and neck cancer treated with definitive chemoradiation receiving either cisplatin or carboplatin with paclitaxel. METHODS A single-institution database was queried for patients with head and neck cancer diagnosed between October 2011 and December 2023 who underwent chemoradiation with either once a week cisplatin (40 mg/m 2 ) or once a week carboplatin (AUC 1) with paclitaxel (30 mg/m 2 ). Cox multivariable analysis (MVA), Kaplan-Meier, Fine-Gray MVA, logistic MVA, and propensity score matching were performed to evaluate treatment outcomes. RESULTS A total of 488 patients were identified. Median follow-up was 43.1 months (95% CI, 41.0 to 45.4). The majority of patients received at least five cycles. Those with older age, former smoking history, and worse performance status were more likely to undergo carboplatin and paclitaxel. Carboplatin and paclitaxel were associated with no statistically significant overall survival (adjusted hazards ratio [aHR], 1.12 [95% CI, 0.69 to 1.82]; P = .64), progression-free survival (aHR, 1.45 [95% CI, 0.96 to 2.19]; P = .08), locoregional failure (aHR, 1.91 [95% CI, 0.85 to 4.32]; P = .12), and distant failure (aHR, 1.33 [95% CI, 0.70 to 2.54]; P = .39) compared with cisplatin. Similar findings were noted on 109 matched pairs as well as subgroups stratified by p16 status. CONCLUSION Our study suggested that those treated with weekly carboplatin and paclitaxel had no statistically significant survival and tumor control outcomes compared with those with weekly cisplatin. Older age and poor performance status were independently associated with the receipt of weekly carboplatin and paclitaxel.

158 Background: We previously reported that olaparib significantly improves radiographic progression-free survival (rPFS) when added to radium-223 for bone-dominant mCRPC in the COMRADE study (NCT03317392). Here, we investigate ctDNA and PSA dynamics by arm from patients on the COMRADE study. Methods: Cell free DNA from banked plasma was sequenced on FoundationOne Monitor as a research use test. ctDNA was quantified as ctDNA tumor fraction (TF). rPFS and overall survival (OS) were assessed by Kaplan-Meier analysis and univariate Cox proportional hazard models, landmarked from the relevant sample collection date; patients with progression before the landmark were excluded. Molecular response (MR) and PSA response (PSA50) were defined as ≥50% decrease from C1D1. Results: Of 113 patients receiving any study treatment, ctDNA results were successfully generated for 102 patients at cycle 1 day 1 (C1D1), of whom 53 were randomized to radium-223+olaparib (Arm A) and 49 to radium-223 alone (Arm B). Across arms, the median ctDNA TF at C1D1 was 16% [Interquartile Range: 1.3-43%]. Across arms, 99 patients had ctDNA results at C2D1: 5 with progression prior to C2D1, 9 patients with no result at C1D1, and 8 with unquantifiable ctDNA change were excluded. ctDNA TF clearance from C1D1 to C2D1 was achieved in 13/77 patients (17%; Arm A: 17%, Arm B: 17%), and 50-99% reduction in 14/77 patients (18%; Arm A: 22%, Arm B: 15%). 15/77 patients (19%; Arm A: 22%; Arm B: 17%) were negative at both timepoints and not included in assessment of MR. MR was associated with significant, favorable PFS (MR: 4.6 months vs No MR: 2.0 months, p=0.01) and OS (MR: 21.2 months vs No MR: 12.2 months, p=0.005) with similar trends within both treatment arms. A greater improvement in rPFS with the addition of olaparib was observed for patients who achieved MR (MR: HR = 0.35 [95% confidence interval (CI): 0.14-0.91]; No MR: HR = 0.65 [95% CI 0.29-1.43]). Similar to TF, baseline PSA was prognostic: when stratified at the median (51.6 ng/mL), patients with lower PSA demonstrated significantly improved rPFS (11.0 vs 3.8 months for low vs high PSA, p&lt;0.0001) and OS (26.6 vs 13.2 months, p&lt;0.0001). Of the 13 patients that ever-achieved PSA50, including after crossover, 69% achieved MR compared to 37% in 49 patients without PSA50. Conclusions: Early MR (by C2D1) was achieved in 35% of patients and strongly associated with improved rPFS and OS while PSA50 responses by C2D1 were not observed in any patients. The rPFS benefit of adding olaparib to radium-223 appeared more evident in those who achieved a MR. Early on treatment ctDNA dynamics in bone-dominant mCRPC may be a valuable tool for treatment decisions with radium-223 therapy. Clinical trial information: NCT03317392 .

Glioblastoma (GBM) is an extremely aggressive and incurable primary tumor of the brain. GBM is characterized by interpatient and intratumoral heterogeneity, making this cancer particularly resistant to therapy and likely to recur. Mapping the complex dynamics that underpin the development and evolution of gliomas with human-based in vitro models is difficult. This study aimed to generate 3D glioma patient-derived tumor constructs (PTCs) using a clinically relevant, Matrigel-free, hyaluronic acid system, evaluate their suitability in drug screening assays, and determine the stability of their genetic profiles compared to originating tumors. In this study, we utilized a synthetically modified hyaluronic acid and gelatin hydrogel system to generate tumor constructs containing cells from clinical glioma biospecimens. PTCs were characterized phenotypically, after which they were deployed in chemotherapy drug screens using temozolomide (TMZ) and a P53 activator compound. Drug responses of these 3D cultures were compared with 2D cultures, as well as PTCs that were generated after passaging in 2D. RNA sequencing was used to evaluate genetic parity between PTCs or 2D cultures with originating tumor tissues, using The Cancer Genome Atlas (TCGA) GBM subpopulations for subcategorizing. PTCs were created successfully from five World Health Organization (WHO) grade 4, two grade 3, and two grade 2 gliomas. PTCs were maintained with high viability. Chemotherapy drug screens demonstrated that expected TMZ responses were observed for Isocitrate dehydrogenase (IDH) mutant diffuse gliomas while drug response was variable for IDH wildtype GBM PTCs. PTCs demonstrated stable drug response over time, while 2D passaging resulted in significant shifts in drug sensitivity. RNA sequencing revealed maintenance of subpopulation signatures for PTCs which clustered with their originating patient tumor tissue. In contrast, 2D cultures largely clustered together regardless of the patient. Our PTC approach utilizes a defined hydrogel biomaterial system that maintains the genotypic and drug response characteristics of patient tumors making this an ideal ex vivo model for translational applications.

<title>Abstract</title> Targeted RNA sequencing (RNAseq) is widely used to detect gene fusions in tumors but clinical diagnostic use of expression data from these panels in fusion-negative cases has been limited. To facilitate this application, we evaluated methods for sequence read counting and gene normalization to optimize them for smaller gene sets. We present comparative methods to derive differential gene expression (DGE) data using ~ 200-gene clinically validated RNAseq fusion panels and compared them to parallel full RNAseq. We compared five methods for read counting, demonstrating that featureCounts is the most rapid and robust. For normalization prior to DGE with DESeq2, we compared five different normalization strategies and showed normalization using the 5 most stably expressed genes provided optimal centralization for these smaller gene sets. DGE output was assessed by principal component analysis (PCA), t-SNE and heatmap-clustering. The final pipeline was validated using PCA and pathway analysis by comparison with full RNAseq separately performed on a common set of challenging tumors with comparable results observed with the targeted gene panel. Overall, we show using an optimized bioinformatic pipeline that usable gene expression data can be obtained from smaller targeted RNAseq panels to maximize the clinical utility of these assays.