Lower Median Overall Survival Research Articles

Characteristics of patients with metastatic malignant melanoma in Colombia: Results of the Epidemiologic Registry of Malignant Melanoma REMMEC ACHO.

e21530 Background: The features and prognostic factors of patients with metastatic malignant melanoma are not well established in our country. Our objective is to collect and analyze the characteristics of a cohort of Colombian patients. Methods: Analytical cohort study based on the Epidemiologic Registry of Malignant Melanoma in Colombia (REMMEC). Data were collected between January 2011 and December 2023. Patients older than 18 years with a confirmed diagnosis of advanced melanoma were included. Descriptive analysis of demographic and clinical characteristics and survival analysis using Cox regression and Kaplan-Meier models were performed. Results: 322 patients were included. Median age was 66.5 years (range 55-76), 56% (180) of patients were men, 87% (280) had advanced disease at diagnosis, most (82%) with non-brain metastases and 51% (164) with multiple organ involvement. Table 1. For first-line treatment, patients received single-agent immunotherapy (37.26%), doublet immunotherapy (10.25%), targeted therapy (9%), and chemotherapy (7.14%), while 29% received best supportive care BSC. In the second line, single agent immunotherapy 9.32%, targeted therapy (4.34%), doublet immunotherapy 3.42%, chemotherapy (5%) and 77% received BSC. In the third line, only 9% (29) of patients were able to receive any therapy. Median follow-up was 16 months (IQR 7-32), median progression-free survival (PFS) was 8 months (IQR 4-35) and median overall survival (OS) was 23 months (IQR 9-66). OS in the first-line setting with immunotherapy as monotherapy was 23 months (IQR 12-40) HR 0.40 P 0.035 and with doublet immunotherapy 16 months (IQR 8-28) HR 0.16 P 0.005 Clinical characteristics associated with lower median OS were brain metastasis (HR 1,95 P 0.001), ECOG 3-4 (HR 5,49 P 0.001) and multiple metastatic disease (HR 2,15 P 0.001). According to acral vs. non-acral histologic type, the median OS was 26 vs. 44 months, respectively (HR 1.30 P 0.26). Conclusions: In our cohort of patients with metastatic melanoma, we found clinical outcomes similar to those reported in the worldwide literature. It is necessary to continue the registry and follow-up of patients to identify specific prognostic factors. [Table: see text]

Clinical value of endoscopic ultrasound sound speed in differential diagnosis of pancreatic solid lesion and prognosis of pancreatic cancer.

Differential diagnosis of pancreatic solid lesion (PSL) and prognosis of pancreatic cancer (PC) is a clinical challenge. We aimed to explore the differential diagnostic value of sound speed (SS) obtained from endoscopic ultrasonography (EUS) in PSL and the prognostic value of SS in PC. Patients with PSL in The Third Xiangya Hospital of Central South University from March 2019 to October 2019 were prospectively enrolled, who obtained SS from PSL. Patients were divided into the PC group and the pancreatic benign lesion (PBL) group. SS1 is the SS of lesions and SS2 is the SS of normal tissues adjacent to lesions. Ratio1 is equal to SS1 divided by SS2 of PSL (ratio1 = SS1/SS2). Eighty patients were enrolled (24 PBL patients, 56 PC patients). SS1 and ratio1 in PC group were higher compared with PBL group (SS1:1568.00 vs. 1550.00, Z = -2.066, p = 0.039; ratio1: 1.0110 vs. 1.0051, Z = -3.391, p = 0.001). The SS1 in PC (Z = -6.503, p < 0.001) was higher compared to SS2. In the nonsurgical group of PC, low ratio1 predicted high overall survival (OS) (7.000 months vs. 4.000 months; p = 0.039). In the surgical group of PC, low SS1 was associated with low median OS (4.000 months vs. 12.000 months; p = 0.033). SS plays a vital role in distinguishing between PBL and PC. Higher SS1 and ratio1 obtained by EUS are more related to PC than PBL. In PC patients, high SS1 may predict pancreatic lesions. In the nonsurgical group of PC, low ratio1 may predict high OS. However, in the surgical group of PC, low SS1 may predict low OS.

Co-Mutational Patterns with BCOR Influences Biological Characteristics and Clinical Outcomes of Myeloid Neoplasms

Introduction BCL6 co-repressor ( BCOR), a tumor suppressor gene located on chromosome X (locus Xp11.4) is involved in hematopoiesis via non-canonical polycomb repressive complex 1 (PRC1). The prevalence of BCOR mutation in myeloid neoplasms (MN) is approximately 5%, and it is also implicated in clonal hematopoiesis. In the 2022 ELN, WHO, and ICC classifications, BCOR is categorized as a myelodysplasia-related gene. Mutational patterns include frequent co-occurrence with DNMT3A and RUNX1 in AML and mutual exclusivity with NPM1 mutations. Although it has been theorized that BCORMT may cooperate preferentially with certain groups of genes, the prognostic significance of the BCOR co-mutational landscape has yet to be fully studied. Methods The total cohort (n = 20149) consists of 624 MN patients (169 primary (p) AML, 136 secondary (s) AML, 84 MDS, 34 MDS/MPN, 66 MPN, and 135 with other MN) from Karmanos Cancer Institute, publicly available metanalytic cohort consisting of various sub-studies (Awada et al., 2021; Kewan et al., 2023), and cohorts from open-access cancer genomics resource cBioPortal and AACR GENIE (v13.1) (Cerami et al., 2012; Gao et al., 2013). Clinical and genomic characteristics were reviewed. Chi-square and T-tests were used for analysis of various parameters as described, and Kaplan-Meier and log-rank methods were used to estimate overall survival (OS). The prevalence of BCORMT, co-occurring mutations, and their outcomes were analyzed based on co-mutational patterns. Results A total of 745 (3.7%) patients carried BCORMT. Male: Female ratio was 1.48, with a median age of 68 ys.(IQR 59-75). BCORMTshowed a trend to be most frequent in pAML compared to other MN (54 vs 46%, p=0.33). BCORMT was less associated with abnormal karyotype vs. BCORWT [41 vs. 51%, p=0.0002]. Median variant allele frequency (VAF) was 45% (IQR 22-69), and most mutations were frameshift (41%) followed by nonsense (27%), and missense (22%). Median OS was not different between BCORWT and BCORMT patients [21.9 vs. 19.6 mo., p=0.089] in the entire cohort. Oncoprint analysis centered around BCOR revealed frequent co-mutations with RUNX1, DNMT3A, TET2 and ASXL1. As a result, the patients were divided into 10 groups (groups A-J), and the OS was analyzed between groups and compared with BCORWT. Patients with BCOR/TET2, BCOR/RUNX1/TET2, and BCOR/ASXL1 (groups G, B, and H resp.) had the lowest median OS with 14.5 mo., 16.7 mo., and 17.4 mo., resp. However, no significant differences in median OS were observed between the compared groups except those involving BCOR/ASXL1 vs. BCOR/Others and BCORWT. BCOR/ASXL1 patients had significantly lower median OS compared to BCOR/Others [17.4 vs. 22.5 mo., p=0.022] and BCORWT [17.4 vs. 21.9 mo., p=0.017]. Further BCORMT and ASXL1MT comutational analysis irrespective of other co-occurring mutations, revealed that in those with BCORMT, ASXL1 co-mutation was seen in 143 (19.2%) patients. BCOR and ASXL1 co-mutation were primarily enriched in primary AML (49%), followed by sAML (25%). Median BCOR VAF was higher than ASXL1 [39 vs. 31%, p&amp;lt;0.0001]. The most associated mutational categories in this subgroup were related to myeloid transcription factors (TF) ( RUNX1, CEBPA; 62%), spliceosome ( SRSF2, U2AF1, SF3B1, ZRSR2; 22%), and DNA methylation family ( DNMT3A, TET2, IDH1/2; 8%). BCORMT/ ASXL1MT/DNA Methylation mutations had poorer median OS compared to BCORMT/ ASXL1MT/Spliceosome mutations [9.2 vs. 17.4 mo., p=0.044]. Whereas BCORMT/ ASXL1MT/Myeloid TF and BCORMT/ ASXL1MT/Spliceosome mutations had no significant survival difference compared to BCORWT, patients with BCORMT/ ASXL1MT/DNA Methylation had worse median OS [9.2 vs. 21.9 mo., p=0.007]. Conclusion This large cohort study confirms common BCOR co-mutation patterns and reveals prognostic differences in patients with co-occurring ASXL1 mutation. We demonstrated BCORMT with ASXL1MT without concurrent RUNX1MT, DNMT3AMT, and TET2MT had poorer overall survival. Furthermore, patients with BCORMT, ASXL1MT, and concomitant DNA methylation-related gene mutations had worse outcomes compared to those with concomitant spliceosome mutation and BCORWT. Our findings suggest that co-mutational patterns of BCOR may further clarify diagnosis and classification schemes, highlighting potential synergies among subcategories of gene mutations and their prognostic value.

A Phase 2 Study with Volasertib for Ven-HMA Relapsed/Refractory Acute Myeloid Leukemia Patients Guided By a Predictive Precision Medicine Platform

Introduction Acute myeloid leukemia (AML) represents a significant clinical challenge, with complex genetic heterogeneity that underlies the variable patient response to existing treatment modalities. While molecular features and novel therapeutic options offer promising solutions, their effectiveness is often compromised by inter-patient and intra-leukemia variability, coupled with an overall lack of biomarkers that can reliably inform therapeutic benefit. Consequently, these therapies yield clinical responses limited to only a subset of patients. Predicting a patient's response before initiating therapy optimizes treatment selection by improving the benefit/risk ratio (therapeutic index) and increasing response rates. This helps avoid treating non-responding patients, thereby reducing the occurrence of adverse effects and minimizing the costs associated with ineffective care. Here, we present an actionable strategy in AML that employs an automated, high-throughput, multi-color flow cytometry-based predictive precision medicine platform (PPMP) offering a genetic biomarker-agnostic approach to identify responders to standard-of-care (SOC) treatments and the polo-like kinase 1 (PLK-1) inhibitor volasertib. Clinical validation of the PPMP To date, we have conducted four studies evaluating the PPMP's predictive performance in myelodysplastic syndromes, adult AML, and pediatric AML with several SOC agents. For all studies, pre-induction blood or bone marrow samples were collected from patients then ex vivo treatment responses of individual leukemic cells were assessed using multi-color flow cytometry. The results were validated with the patient's actual clinical response as reported by physicians and indicated high precision-with positive predictive values (PPVs) of 83-100%. These findings help establish a PPMP-based pursuit of investigational therapies to enhance their therapeutic utility in distinct response groups. Case study: Volasertib One application of this approach involves the revival of volasertib, a PLK-1 inhibitor with demonstrated activity in AML, that was discontinued by Boehringer Ingelheim (BI) after failing its Phase 3 study. A BI Phase 2 study showed volasertib combined with low-dose cytarabine (V+LDAC) delivered a complete response (CR) + CR with incomplete count recovery (CRi) rate of 31.0% compared to 13.3% from LDAC monotherapy, and higher overall survival (OS). Similarly, in a global Phase 3 study a CR + CRi rate for V+LDAC (27.7% overall response) compared to Placebo+LDAC (17.1%) was reported. However, the Phase 3 study showed a higher frequency of fatal events with V+LDAC, especially in non-responders, resulting in lower median OS. By accurately pinpointing clinical responders, the integration of PPMP aims to identify those patients deriving clinical benefit (CR or CRi) from volasertib. Clinical trial design We plan on initiating a Phase 2a single-arm, open-label clinical trial in AML with volasertib in Ven-HMA relapsed or refractory patients, while co-developing PPMP as a companion diagnostic to selectively enroll predicted responders in a follow-up Phase 2b study (Figure 1). Intially, 20-30 patients will be enrolled. Once sufficient responders are achieved and certain performance thresholds of the drug sensitivity platform are met, an additional 20-30 patients will be enrolled, utilizing the companion diagnostic to selectively enroll predicted responders. The primary objectives will be focused on efficacy and safety of intravenous volasertib (possibly in combination with another drug) in patients with relapsed/refractory AML. Secondary objectives will include ex vivo response data collection to optimize the diagnostic parameters for the Phase 2b study. Primary Phase 2a endpoints include AML disease response assessment per pre-specified criteria. Secondary endpoints include an assessment of the diagnostic performance characteristic of Notable's drug sensitivity score in predicting in vivo volasertib clinical response. Specific strategies, including tailored dosing, robust infection control, and carefully selecting drug combination partners are designed to mitigate the adverse events observed in BI's Phase 3 trial and maximize volasertib's therapeutic impact regarding both efficacy and safety.

Co-Occurring Mutations in ASXL1 and SRSF2 Define a Unique, Prognostically Relevant Chromatin-Spliceosome Gene Signature in De Novo acute Myeloid Leukemia

Background: Prior studies with extensive acute myeloid leukemia (AML) molecular profiling identified various subgroups wherein co-mutations in genes related to chromatin regulation and RNA splicing showed no survivors, irrespective of age or treatment. Within the chromatin-spliceosome family, co-mutations of ASXL1 and SRSF2 are linked to poor outcomes. However, the representation of this co-mutational pair in de novo, secondary, and therapy-associated AML is not well described. Also, there is no evidence to demonstrate if HSCT would alter poor prognostic outcomes in this unique molecular subgroup of AML. We sought to assess the clinicogenomic characteristics of ASXL1/ SRSF2 co-mutation and its outcomes in a large, well-annotated, sequenced cohort of real-world AML patients. Methods: We conducted a retrospective analysis of adult AML patients with ASXL1 MT/ SRSF2 MT by screening well-annotated public databases, cBioPortal (Cerami et al., 2012) and AACR GENIE (v 13.1), and expanded with a published metanalytic cohort of various sub-studies from Cleveland Clinic Foundation from 2012-2021 (Awada et al., Blood 2021, Kewan et al., Nature Communications, 2023). We analyzed the NGS data in the context of baseline clinical parameters, coexisting mutations, variant allele frequencies, karyotype, and AML subtypes. The primary endpoint was overall survival (OS), and secondary outcomes included survival based on AML subtype, karyotype, and hematopoietic stem cell transplant treatment (HSCT). The chi-square test was used to study various described parameters, and Kaplan-Meir curves were used for survival analyses. Results: We screened a total of 15,742 adult patients with AML, and 2,471 eligible patients were separated into 3 cohorts: 280 (11.3%) patients with ASXLMT/SRSF2 MT,1,025 (41.5%) patients with ASXLMT/ SRSF2WT and 1,166 (47.2%) patients with ASXLWT/ SRSF2MT. In addition, three AML subtypes were established: de novo AML (dnAML), secondary AML (sAML), and therapy-associated AML (tAML). The median age of the co-mutated cohort was 70.1 ys. [range 42-100 ys.], compared to the ASXL1MT [17-100 ys., p=0.0046] and SRSF2MT cohorts [25-99 ys., p=0.5]. Females were more prominently represented in the ASXL1MT cohort compared to the SRSF2MT cohort [47% vs 30%, p&amp;lt;0.0001]. All three cohorts were predominantly enriched by dnAML (69%, 70%, and 67%), the ASXL1MT cohort had the most tAML (2.2%), and sAML enriched the SRSF2MT cohort (31%). Abnormal karyotype enriched the ASXL1MT/ SRSF2WT cohort compared to SRSF2MT [50% vs 39%, p=0.0001] and equivalent in ASXL1MT cohorts (50% vs 51%, p=0.06]. Median OS was driven in part by the ASXL1MT clone and lowest for the co-mutated compared to the ASXL1MT [12.0 vs 12.5 mo., p=0.0055] and SRSF2MT cohorts [12.0 vs 17.5 mo., p =&amp;lt;0.0001]. When divided by AML-subtype, dnAML had the lowest median OS in the co-mutated, compared to the ASXL1MT [12 vs 15 mo., p =0.03] and the SRSF2MT cohorts [12 vs 17 mo., p =0.02]. sAML had nearly equivalent survival across all cohorts (10.0 vs 9.3 vs 9.4 mo.), and although tAML offered numerically better survival (NE vs 8.7 vs 17.5 mo.), it was not significant. Normal karyotype offered a numerical survival advantage (NE vs 14.39 vs 16.85 mo.). The median number of mutations in the co-mutated cohort was 4 (range 3 - 7), Fig 1(A). The most common co-occurring mutations in this cohort were RUNX1 (78%), TET2 (48%), IDH2 (43%), NRAS (16%), and CEBPA (15%). 21 patients were transplant-eligible from the co-mutated cohort, with median OS after HSCT being 33 vs 12 mo. without HCT (p =0.0010), Fig 1 (B). Conclusions: ASXL1/ SRSF2 co-mutated patients represent a unique chromatin-spliceosome signature, most prominently in de novo AML, associated with a significantly lower OS. Therefore, it must be identified at diagnosis for improved prognostic assessment and potential therapeutic implications. HSCT can provide longer-term survival in these patients. This represents the largest reported cohort of patients with ASXL1/ SRSF2 co-mutated AML. Further studies are warranted to validate the chromatin-spliceosome signature and prognosis.

Elucidating the molecular role of MUC5B in progressive lung adenocarcinoma: Prospects for early diagnosis.

Gel-forming mucin MUC5B is significantly deregulated in lung adenocarcinoma (LUAD), however, its role in tumor progression is not yet clearly understood. Here, we used an integrated computational-pipeline-initiated with gene expression analysis followed by network, functional-enrichment, O-linked glycosylation analyses, mutational profiling, and immune cell infiltration estimation to functionally characterize MUC5B gene in LUAD. Thereafter, clinical biomarker validation was supported by the overall survival (OA) and comparative expression profiling across clinical stages using computational algorithms. The gene expression profile of LUAD identified MUC5B to be significantly up-regulated (logFC: 2.36; p-value: 0.01). Network analysis on LUAD interactome screened MUC5B-related genes, having key enrichment in immune suppression and O-linked glycosylation with serine-threonine-rich tandem repeats being highly glycosylated. Furthermore, positive correlation of mutant MUC5B with immune cells in tumor microenvironment (TME) such as cancer-associated fibroblasts and myeloid-derived suppressor cells indicates TME-mediated tumor progression. The positive correlation with immune inhibitors suggested the enhanced tumor proliferation mediated by MUC5B. Structural stability due to genetic alterations identified overall rigid N-H-backbone dynamics (S2 : 0.756), indicating an overall stable mutant protein. Moreover, the low median OA (<50 months) with a hazard ratio of 1.4 and clinical profile of MUC5B gene showed high median expression corresponding to lymph node (N2) and tumor (T3) stages. Our study concludes by highlighting the functional role of O-glycosylated and mutant MUC5B in promoting LUAD by immune suppression. Further, clinical gene expression validation of MUC5B suggests its potential role as a diagnostic biomarker for LUAD metastasis.

Efficacy and toxicity of stereotactic body radiotherapy for un-resectable stage III non-small cell lung cancer patients unfit for concurrent chemoradiation therapy: a retrospective study

BackgroundIn this study, we evaluated the efficacy and toxicity of stereotactic body radiotherapy (SBRT) as replacement strategy of conventionally fractionated radiation therapy in stage III non-small cell lung cancer (NSCLC) patients unfit for concurrent chemoradiation therapy (CRT).MethodsWe analyzed the clinical outcomes in patients with unresectable stage III NSCLC who received SBRT from January 1, 2013 to December 31, 2018. Both induction and consolidation chemotherapy were allowed. The survival rates and toxicities were calculated using the Kaplan-Meier method, and potential risk factors were investigated by multivariate Cox regression.ResultsA total of 213 consecutive patients who had received SBRT were enrolled. The median overall survival (OS) and progression-free survival (PFS) were 36.5 months and 16.1 months respectively. The estimated 1-, 2- and 3-year OS rates were 90.6%, 73.7% and 52.0%, respectively and the corresponding PFS rates were 69.5%, 25.4% and 15.0%, respectively. Treatment failures were largely (n = 151, 70.9%) distant metastases, with low rates of local (n = 74, 34.74%) and regional (n = 76, 35.68%) recurrences. In 13.1% patients (n = 28), ≥ grade (G) 3 toxicities were identified, including radiation pneumonia (n = 20, 9.4%) and bronchopulmonary hemorrhage (n = 8, 3.8%). None of the patients suffered from ≥ G 3 late toxic effects. Compared with patients with peripheral tumors, patients with central tumors had lower median OS (P<0.001) and the biological effective dose (BED) was not a predictor for OS.ConclusionsSBRT combined with chemotherapy for stage III NSCLC produced favorable treatment outcomes with acceptable toxicity. For patients with central tumors, an appropriate BED reduction can be considered. Further studies are warranted.Trial registrationRetrospectively registered.

Evaluating depth of disparities in relation to relative survival rates: Analysis of SEER data.

6602 Background: Prior studies have identified widening survival disparities between Black vs White patients (pts) in solid tumors with higher 5-year relative survival rates (RSR), a surrogate for higher amenability to treatment (Tehranifar et al., 2009). Given major advancements in treatment for hematologic malignancies leading to higher RSR, we sought to evaluate whether disparities worsened with higher RSR, especially among Black pts compared to White pts, in the modern era of therapy. We hypothesized that racial disparities would be larger in malignancies with higher amenability, as measured by 5-year RSR. Methods: We identified first hematologic malignancies among pts ages ≥18 years diagnosed between 2009-2019 in a collection of 17 Surveillance, Epidemiology and End Results (SEER) Program registries. We treated RSR as a continuous variable. Cox proportional-hazards model was used to correlate RSR and race with overall survival (OS) controlling for other pt characteristics. The interaction between RSR and race was included in the model to test if the racial effect on OS differed at various RSR levels. Results: We identified 363,340 pts who met inclusion criteria. Median age was 66 years and 55% were male. 82% were White and 10% Black. With a median follow-up of 48 months (mos), median RSR was 68.2% and median OS was 101 mos (95% CI 100-102 mos). Black pts had a lower median RSR than White pts, 63.8% vs 68.9%, and lower median OS, 90 mos (95% CI 87-93 mos) vs 99 mos (95% CI 98-100 mos). On univariable analysis, all variables were statistically significant given the large sample size. On multivariable analysis (MVA), Black pts had a higher risk of death than White pts. The interaction between 5-year RSR and race was highly significant (p=&lt;0.01, not shown in Table), as indicated by slightly increasing hazard ratios (HRs) reflecting Black-White survival differences with increasing RSR level (i.e., as RSR increased, Black pts had slightly worse OS than White pts) (Table). Conclusions: We hypothesized that with increasing RSR, Black-White disparities might increase, as all effective therapies which contribute to improved RSR might not be equitably available to all populations. We observed that statistically significant disparities were present across RSR levels and increased only minimally for those with hematologic malignancies with higher RSR. In conclusion, disparities are prevalent in hematologic malignancies despite the degree of amenability to treatment. [Table: see text]

Survival benefit and optimal timing for re-resection in patients with gallbladder cancer: A National Cancer Database analysis.

614 Background: Often times, gallbladder cancer is diagnosed incidentally after cholecystectomy. Most patients will then undergo re-resection for potential residual disease, however overall survival (OS) benefit data in this scenario is variable. Further, limited literature regarding optimal time to re-resection exists. Prior studies found the optimal time to re-resection to be approximately 4-8 weeks after initial diagnosis; however, additional data is needed to further validate these findings. In this National Cancer Database(NCDB) analysis we compare OS in patients diagnosed with T1b – T3 gallbladder cancer who underwent re-resection and evaluate if time to resection impacts OS. Methods: We reviewed the NCDB for patients who had received initial cholecystectomy for gallbladder cancer and were subsequently eligible for re-resection based on tumor stage (T1b-T3 disease) from 2004-2018. We excluded patients with metastatic M1 disease and T0, T1a, T1, or T4 disease. Patients with re-resection were further subdivided into four cohorts based on time to re-resection: 0-4 weeks, 5-8 weeks, 9-12 weeks and &gt;12 weeks. We used a Cox proportional hazards ratio to identify factors associated with worse survival and logistic regression to evaluate characteristics associated with re-resection. OS was calculated using Kaplan Meier curves. Results: 791 (5.82%) patients received re-resection of 13,601patients meeting inclusion and exclusion criteria. Cox proportional hazards analysis showed a Comorbidity Score of 1 was associated with worse survival. Patients with higher Comorbidity Scores (1,2, or 3) and treatment at comprehensive community, integrated or academic cancer programs were less likely to undergo re-resection (in comparison to community programs). Patients treated at an Urban facility or diagnosed from 2009-2018 were more likely to undergo re-resection. The cohort with no re-resection had the lowest median OS [17.61 months; CI 17.05- 18.20] and re-resection showed significantly improved OS [HR 0.87; 95 CI 0.77-0.98; p=0.02]. Significantly improved survival was noted when re-resection was completed at 5-8 weeks [HR 0.67; CI 0.57- 0.81], 9-12 weeks [HR 0.64; CI 0.52- 0.79], or &gt;12 weeks [HR 0.61; CI 0.47- 0.78]. Conclusions: Despite the retrospective nature and small sample size of our study, the results are consistent with prior studies depicting a survival benefit with re-resection. Additionally, optimal timing to re-resection supports previous data showing a clear benefit at any time &gt;4 weeks. However, there was no significant survival difference as to whether re-resection was completed at 5-8 weeks, 9-12 weeks, or &gt; 12 weeks post initial cholecystectomy. Decreased post-operative inflammation and accurate staging at &gt;4 weeks may account for improved survival with later re-resection; however, future investigations are warranted to delineate underlying causes.

P11.45.B Improved overall survival following Stereotactic Radiosurgery for brain metastases - a single institution experience

Abstract Background Brain metastases are increasingly common due to longer survival associated with advancements in treatment. Approximately 40% of cancer patients are diagnosed with brain metastases at some point during their disease. Stereotactic radiosurgery (SRS) avoids the neuro-cognitive toxicity associated with whole brain radiotherapy and has been increasingly offered as a treatment alternative for brain metastases. Combined with developments in systemic treatments, this approach has resulted in improved overall survival (OS). This study reviewed patients treated with single fraction SRS at our institution with a primary endpoint of overall survival. Material and Methods A retrospective review determined overall survival for 237 patients who received single fraction SRS for 451 brain metastases from solid tumours between 1st January 2017 and 31st December 2021. Primary tumour sites were classified as breast, kidney, colorectal, melanoma, lung or other. SPSS v.27 was used for Kaplan Meier OS determination. The median follow up was 10.3 months. Cox regression analysis assessed the association between Gross Tumour Volume (GTV) and OS. Results In this patient cohort, 60% (N=142) were female and 40% (N=95) were male, with a median age of 63 [32-85]. 63.7% (N = 151) had a solitary metastasis. Patients received a single fraction of 15, 17.5 or 20 Gy (prescribed to 80% isodose) dependent on the planning target volume (PTV) size and whether it was initial treatment or re-treatment. 71% of all patients were alive at 6 months with median OS of 12.0 months [10.6-13.4]. Primary tumour site significantly affected OS (Log rank, Chi squared 15.656, p0.008) with breast cancer patients (N=58) surviving longest with a median OS 16.0 months [13.6-18.4] followed by melanoma median OS 15.0 months [7.6-22.4], kidney cancer patients (N = 24) median OS 12.0 months [8.3-15.7] and lung patients (N=87) median OS 10.0 months [8.9-11.3]. The lowest median OS was for colorectal patients at 7.0 months [1.4-12.6]. However, considering the small sample size, N = 15, more data is needed to confirm the significance. The larger the GTV volume the lower the survival time (Chi squared 8.692, p 0.003). Conclusion 71% of patients had an OS of 6.0 months or more with a median of 12.0 months. As expected, primary tumour site has a significant impact on OS, with breast cancer patients living longest. In addition, increasing GTV size is associated with significantly worse survival. Given the improved survival for these patients, the avoidance of neuro cognitive decline remains of paramount importance and outcomes for these patients need to be reported in future work.

High rates of treatment stage migration for early hepatocellular carcinoma and association with adverse outcomes: An Australian multicenter study.

Background and AimThe rate of contraindications to percutaneous ablation (PA) for inoperable early hepatocellular carcinoma (HCC) and subsequent outcomes is not well described. We investigated the prevalence and outcomes of inoperable early HCC patients with contraindications to PA, resulting in treatment stage migration (TSM).MethodsBarcelona Clinic Liver Cancer (BCLC) 0/A patients diagnosed between September 2013 and September 2019 across five hospitals were identified. Primary endpoint was proportion of BCLC 0/A HCCs with contraindications to PA. Secondary endpoints included overall survival (OS), local tumor control (LTC), and recurrence‐free survival (RFS). The causal effects of PA versus TSM were assessed using a potential outcome means (POM) framework in which the average treatment effects (ATEs) of PA were estimated after accounting for potential selection bias and confounding.ResultsTwo hundred twenty patients with inoperable BCLC 0/A HCC were identified. One hundred twenty‐two patients (55.5%) had contraindications to PA and received TSM therapy, 98 patients (44.5%) received PA. The main contraindication to PA was difficult tumor location (51%). Patients who received TSM therapy had lower median OS (2.4 vs 5.3 years), LTC (1.0 vs 4.8 years), and RFS (0.8 vs 2.9 years); P < 0.001, respectively, compared with PA. The ATE for PA versus TSM yielded an additional 1.11 years (P = 0.019), 2.45 years (P < 0.001), and 1.64 years (P < 0.001) for OS, LTC, and RFS, respectively. Three‐year LTC after PA was suboptimal (65%).ConclusionOur study highlights high rates of contraindication to PA in early HCCs, resulting in TSM and poorer outcomes. The LTC rate for PA appears suboptimal despite being considered as curative therapy. Both findings support the exploration of improved treatment options for early HCCs.

Abstract 3668: Socioeconomic disparities in healthcare utilization and overall survival among patients with cancer: Application of area-level socioeconomic status in a nationwide electronic health record-derived database

Abstract Introduction: While lower socioeconomic status (SES) is associated with worse cancer outcomes, most electronic health records (EHRs) lack documentation of SES. Here we apply an area-level SES measure to an EHR-derived database to evaluate representativeness according to SES. We then examine socioeconomic disparities in the timeliness of healthcare utilization (biomarker testing and systemic treatment) and overall survival (OS) in 3 common cancers. Methods: This retrospective study uses the nationwide Flatiron Health EHR-derived de-identified database of cancer patients who have clinical activity between January 2011-August 2021. Census block group data from the American Community Survey (2015-2019) was used to measure SES per the Yost Index (incorporating income, home values, rental costs, poverty, blue-collar employment, unemployment, and education information). SES quintiles were determined from the US population and then applied to patients based on their residential addresses. Our database included 2,067,644 cancer patients from community practices. Patients with advanced non-small-cell lung cancer (aNSCLC, n=51,596), metastatic breast cancer (mBC, n=18,268), and multiple myeloma (MM, n=8,246) were sampled and followed from advanced, metastatic, or initial diagnosis date, respectively. Differences were evaluated using Χ2 tests for categorical variables and log-rank tests for Kaplan-Meier survivor functions. Results: Compared to the US population, our database of cancer patients has a similar SES distribution (differences &amp;lt;3%), capturing cancer patients living in the most (Q1) and least affluent areas (Q5) of the country. Yet, among the 1.5% of cancer patients who participated in clinical trials, only 15.2% lived in the least affluent areas. aNSCLC and mBC patients living in the least affluent areas were less likely to receive biomarker testing within 30 days of index diagnosis than those in the most affluent areas (59.4% vs. 68.7%; 74.9% vs. 81.0%, both p&amp;lt;.01). Similar patterns were observed in receipt of systemic treatment within 60 days of index diagnosis (aNSCLC: 58.9% vs. 64.9%; mBC: 76.0% vs. 80.1%, both p&amp;lt;.01). No differences in healthcare utilization were observed among MM patients. Patients in the least affluent areas had lower median OS (months) than those in the most affluent areas (aNSCLC: 10.8 [95% CI: 10.4-11.3] vs. 12.2 [95% CI: 11.8-12.7]; mBC: 28.0 [95% CI: 26.6-29.5] vs. 34.5 [95% CI: 33.1-36.9], MM: 57.4 [95% CI: 53.5-61.5] vs. 67.5 [95% CI: 62.5-76.4]; all p&amp;lt;.01). Conclusion: Lower SES was associated with reduced clinical trial participation, less timely healthcare utilization, and worse OS. Making SES available in real-world data can support the development of inclusive clinical trials and inform interventions to reduce cancer care disparities. Citation Format: Jenny S. Guadamuz, Xiaoliang Wang, Jeremy Snider, James Walters, Rebecca A. Miksad, Gregory S. Calip. Socioeconomic disparities in healthcare utilization and overall survival among patients with cancer: Application of area-level socioeconomic status in a nationwide electronic health record-derived database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3668.

Clinical outcomes in immunotherapy and chemotherapy in minority populations with non-small cell lung cancer (NSCLC).

e20508 Background: Lung cancer is the leading cause of cancer deaths for Hispanics (HIS). Similarly, non-Hispanic blacks (NHB) are often disproportionately represented among cancer deaths compared to other racial/ethnic groups with lung cancer being the second most common cancer in black men and women, as well as the leading cause of cancer death. Despite these statistics, HIS and NHB remain underrepresented in non-small cell lung cancer (NSCLC) research. The aim of this study was to determine if there was a difference in outcomes between HIS, NHB and NH Whites (NHW) who had NSCLC and were treated with surgery, immunotherapy or chemotherapy. Methods: We studied 645,221 observations from the 2004-2018 National Cancer Database (NCDB), categorized as HIS, NHB or NHW, who received surgery, immunotherapy or chemotherapy for NSCLC. Categorical variables were analyzed using Pearson’s chi-square test or Fisher’s exact test. Continuous variables were analyzed using ANOVA. Survival outcomes were assessed using a Cox regression model and Kaplan-Meier curves with log-rank tests. Results: Regardless of treatment types, HIS had the highest median overall survival (OS) compared to other groups (NHW: 14.7 months; NHB: 15.0 months; HIS: 16.4 months) (P &lt; 0.001). Regardless of the type of systematic therapy received (immunotherapy or chemotherapy), HIS had the highest median OS (P &lt; 0.001) with HIS in the immunotherapy cohort having the highest survival advantage of all other race/ethnicity and chemotherapy groups. Multivariate Cox regression model further support the survival advantage of HIS compared to NHW (HR = 0.86; P = 0.009). OS was also assessed between patients who received surgery and/or chemotherapy. Patients who received a combination of surgery and chemotherapy had the highest OS compared to patients who underwent surgery only or received chemotherapy only. Among the cohort who received both, HIS had the highest median OS (NHW: 55.2 months; NHB: 55.5 months; HIS: 61.5 months). The surgery only cohort had the next highest median OS of all treatment groups; however, the HIS ethnicity group was non-estimable due to the small sample size. Of all three treatment groups, the chemotherapy only cohort had the lowest median OS while HIS had the highest median OS (NHW: 11.8 months; NHB: 12.9 months; H: 13.5 months) (P &lt; 0.001). Conclusions: Results of our study suggest immunotherapy may offer an increased survival advantage for HIS and NHB compared to chemotherapy. For patients receiving chemotherapy, a combination of surgery and chemotherapy may offer a greater survival advantage for NSCLC patients. Hispanic ethnicity was associated with better survival regardless of the type of treatment received.

Association of BRAF V600E mutation with survival in patients with metastatic mismatch repair-deficient colorectal cancer.

174 Background: Colorectal cancer (CRC), while one of the most common cancer diagnoses, can behave heterogeneously based on molecular characteristics. A subset of patients (pts) with CRC are characterized with mismatch repair deficiency (MMR-d), these pts exhibit encouraging responses to immunotherapy. The predictive nature of various factors, such as BRAF status, age, and MMR-D protein loss type, have been investigated in pts with MMR-d CRC. However, the prognostic role of these factors has not been well established. The purpose of this study was to identify characteristics that influence survival in MMR-d mCRC. Methods: This study evaluated pts with MMR-d mCRC in the Flatiron database. Overall survival (OS) was determined from date of diagnosis of stage IV disease to date of death and stratified based on age greater than or less than 50 years, BRAF mutation status, RAS mutation status, and type of MMR gene loss. For statistical analysis, the Chi-Square test was implemented to determine the prognostic significance of clinical and molecular features. Univariate and multivariate analyses were determined through the Cox regression model. Results: There were 1,101 pts in the study. The majority of pts were older than 50 (79.7%), Caucasian (75%), and had ECOG 0-1 (83.4%). Among the 803 pts with known BRAF status, 44.3% (n=356) had BRAF V600E mutation and 55.7% (n=447) were BRAF wildtype. Pts with BRAF V600E mutation had OS of 18.9 months vs. 33.2 months for pts with wild type BRAF (HR 1.52, 95% CI: 1.25-1.86, p&lt;0.001). Pts older than 50 had a lower median OS vs. those who were ≤50 at 21.4 months vs. 38.7 months (HR 1.66, 95% CI: 1.33-2.07, p&lt;0.001). When comparing MSH2/MSH6 mutations to MLH1/PMS2, a trend towards improved OS was seen with median survival of 35.2 months vs. 22.7 months, respectively (HR 0.79, 95% CI: 0.61-1.02, p=0.067). On multivariate analysis, BRAF mutation and older age continued to be associated with differences in survival, while KRAS mutation and specific MMR gene loss did not. Conclusions: BRAF V600E mutation and age greater than 50 are associated with decreased survival for pts with MMR-D mCRC. KRAS mutations and specific MMR alterations are not associated with differences in survival.

Preoperative Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and CEA as the Potential Prognostic Biomarkers for Colorectal Cancer.

Background This study was to evaluate the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) in colorectal cancer (CRC) patients and to identify the potential and easily accessible prognostic biomarkers for CRC. Methods We retrospectively reviewed altogether the records of 330 CRC patients according to inclusion criteria. The clinical characteristics include age at diagnosis, body mass index (BMI), preoperative CEA level, neutrophil , lymphocyte, and platelet count, tumor primary site and size, clinical pathological TNM stage, and survival status were recorded through the review of medical records. The overall survival (OS) was calculated using the Kaplan–Meier method. The Cox proportional hazards model was used for the univariate and multivariate analysis to evaluate the prognostic factors of CRC. Results A total of 330 patients were finally included in the current study. The mean follow-up duration was 32.8 ± 19.1 months (range, 0.1–67.7). Compared with the median OS, preoperative high NLR, PLR, and CEA, and low BMI had lower median OS. The NLR and PLR value rise indicates lower median OS in stage I-II CRC; however, the NLR value and CEA level rise indicates lower median OS in stage III-IV CRC. Preoperative high NLR, PLR, and CEA level and low BMI have poorer OS by univariate analysis. By multivariate analysis, the age, sex, N, M stage, and BMI demonstrated independently influence the OS of CRC. NLR was an independent predictor of stage I-II CRC, and the CEA level was an independent predictor of stage III-IV CRC. Conclusions Our results show that preoperative high NLR, PLR, CEA, and low BMI had poorer OS, NLR was an independent predictor of stage I-II CRC, and the CEA level was an independent predictor of stage III-IV CRC.

Экспрессия PD-L1 и PU.1 в злокачественных опухолях из оболочек периферических нервов

Introduction. Malignant peripheral nerve sheath tumors (MPNSTs) belong to a rare heterogeneous group of aggressive neoplasms of mesenchymal origin. The relationship between the PD-L1 expression and development and prognosis of MPNSTs has not yet been determined. In addition, it is yet to explore the role of tumor microenvironment, in particular tumor-associated macrophages, in solid tumors. The aim of the study was to determine the relationship between (1) PD-L1 expression and the nuclear marker of PU.1 expression in stromal cells and (2) overall survival (OS) and recurrence-free survival (RFS) in patients with MPNSTs. Materials and methods. The retrospective study included 46 adult patients with MPNSTs who underwent surgical or combined treatment from 1998 to 2021 at the N.N. Blokhin Oncology Research Center. We analyzed clinical and morphological parameters as well as the outcomes of surgical treatment. Immunohistochemistry was used to detect the expression of PD-L1, PU.1, and Ki-67. Results. We found positive PD-L1 staining in 28% of cases. PU.1 expression was observed in all samples. We showed a statistically significant correlation between PU.1 and PD-L1 expression levels. At a median follow-up of 37 months, PD-L1 positive status was associated with a lower median OS and RFS in the group of patients with grade III tumors (p=0.0003 and p=0.004, respectively). The median OS for tumors with high and low number of PU.1+ cells was 21 and 78 months, respectively (p&lt;0.0001). Conclusion. To the best of our knowledge, this is the first study to describe the prognostic value of the macrophage marker PU.1 in patients with MPNST. High levels of PU.1+ cells, regardless of the tumor grade, and PD-L1 expression &gt;1% of tumor cells in the patients with poorly-differentiated MPNSTs, produced a negative effect on OS and RFS. The analyzed expression of these markers can be used in prognostic tests and developing novel therapeutic treatment options. Keywords: malignant peripheral nerve sheath tumor, PD-L1 immunohistochemistry, PU.1, surgical treatment

Immunonutritive Scoring for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Evaluation of the CALLY Index.

Simple SummaryThe novel CRP–albumin–lymphocyte (CALLY) index has been identified as a highly predictive tool for stratification of patients with hepatocellular carcinoma (HCC) who have undergone tumor resection. This study aimed to validate the predictive ability of the CALLY index in patients with HCC treated with transarterial chemoembolization (TACE). The CALLY index was an independent prognostic predictor for overall survival. However, the CALLY index was not superior to other immunonutritive and inflammation scoring systems in predicting the median OS, although all of the individual parameters of the CALLY index were predictive for the median OS. Thus, future studies should re-evaluate the mathematical calculation of the index for patients with HCC undergoing TACE.The novel CRP–albumin–lymphocyte (CALLY) index is an improved immunonutritive scoring system, based on serum C-reactive protein (CRP), serum albumin, and the lymphocyte count. It has shown promise as a prognostic index for patients with hepatocellular carcinoma (HCC) undergoing resections. This study evaluated the prognostic ability of the CALLY index for patients with HCC undergoing transarterial chemoembolization (TACE). We retrospectively identified 280 treatment-naïve patients with HCC that underwent an initial TACE at our institution, between 2010 and 2020. We compared the CALLY index to established risk factors in univariate and multivariate regression analyses for associations with median overall survival (OS). A low CALLY score was associated with low median OS (low vs. high CALLY: 9.0 vs. 24.0 months, p < 0.001). In the multivariate analysis, the CALLY index remained an independent prognostic predictor (p = 0.008). Furthermore, all factors of the CALLY index reached significance in univariate and in-depth multivariate analyses. However, the concordance index (C-index) of the CALLY index (0.60) was similar to the C-indices of established immunonutritive and inflammation scoring systems (range: 0.54 to 0.63). In conclusion, the CALLY index showed promise as a stratification tool for patients with HCC undergoing TACE. Notably, the CALLY index was not superior to other immunonutritive and inflammation scoring systems in predicting the median OS. Thus, future studies should re-evaluate the mathematical calculation of the index, particularly the contributions of individual parameters.

Disease Progression on Ibrutinib Therapy Is Associated with a Poor Clinical Outcome in Chronic Lymphocytic Leukemia (CLL) Patients Managed in Standard Clinical Practice

Introduction: Ibrutinib is an irreversible Bruton Tyrosine Kinase (BTK) inhibitor that has shown efficacy in the treatment of CLL as a front-line therapy or in patients with relapse/refractory (RR) disease. Anecdotally, accelerated disease progression and refractoriness to subsequent therapies in CLL or other B-cell malignancies patients treated with ibrutinib has been observed. In our present contribution, we studied in a real-world patient population the clinical outcome of CLL patients treated with ibrutinib who discontinued therapy. Methods: We conducted a comprehensive retrospective analysis on CLL patients receiving ibrutinib at our Institute. Demographic characteristics, response to subsequent therapies, and results of FISH analysis were obtained. Correlation between clinical outcomes and status on ibrutinib therapy (responding, progressing, or discontinuing due to toxicity) was performed. Statistical analysis was carried out in SPSS v20. Chi Square, Fisher's exact test were used to compare categorical data, Kaplan Meier and Log rank tests for time to event analysis and Cox regression for univariate analysis. Results: A total of 70 CLL patients treated with ibrutinib were followed for a median period of 19.4 mo [ range 0.3 - 41.3]. Sixty-three patients had RR CLL and 7 received ibrutinib as frontline therapy. Our patients had a median age of 67.9 years (46 - 92), a majority had advanced stage disease (Rai stage 3 - 31.4%, Rai stage 4 - 41.4%). Median number of prior treatments was 2 (range 0-7). Overall response rate (ORR) to ibrutinib was 52.8% (complete response [CR] - 11.4%, partial response [PR] - 41.4%]. Additionally, stable disease [SD] was present in 25.7% leading to a Clinical Benefit Rate (CBR) of 78.5%. A total of 25 (38%) patients discontinued therapy. Reasons for discontinuation included progressive disease (PD) in 13 (52%) (5 with Richter's transformation [RT]), drug toxicity (DT) in 7 (28%), and other reasons in 5 (20%) patients. DTs included atrial fibrillation (n=2), sepsis (n=2), pneumonia (n=1), congestive heart failure (n=1) and fatigue (n=1). Other reasons for discontinuation were other terminal cancer (n=2), patient preference, alcoholism and insurance issues. Univariate analysis showed an increased risk of discontinuation associated with del(13q) (HR 1.56, 95%CI 0.7-3.7, p=0 .32), ATM deletion (HR 1.32, 95%CI 0.5-3.4, p=0 .57), Unmutated IgH (HR 3.5, 0.5-27.3, p=0 .23) though none reached statistical significance. We did not observe an increased risk of discontinuation in patients with del(17p) (HR 0.80, 95%CI 0.3-2.7, p=0 .72). Cytogenetic data after ibrutinib discontinuation was available in 12 patients and showed new onset del(13q) (n= 3), del(17p) (n= 4) and ATM deletion (n= 1) including 1 patient who had complex cytogenetics (≥3 cytogenetic abnormalities). In patients who discontinued therapy, we observed a mortality rate of 72% (18/25) with a median overall survival (OS) of 17.8 mo (95% CI, 7.4-28.2); in comparison, median OS was not reached in patients who remained on therapy (p <0.05). A lower median OS was observed in patients who discontinued due to DT (5.9 mo, 95% CI, 3.9-8), compared to those with RT (11.5 mo, 95% CI 3.1-20), PD (18.2 mo, 95%CI 3.8-32.6) though this was not statistically significant (p= 0.117). Despite trends towards lower median OS in patients who discontinue ibrutinib, univariate analysis did not show a statistically significant association with del(13q) (HR 1.8, 95%CI 0.7-5, p=0 .248), ATM deletion (HR 1.32, 95%CI 0.5-3.9, p=0 .61), Unmutated IGH (HR 1.08, 95%CI 0.13-9, p=0 .94), and ZAP70+ (HR 1.15, 95%CI 0.36-3.64, p=0 .81). Two patients had complex cytogenetics with a median OS of 1.5 mo (HR 4.5, 95%CI 0 .9-22.4, p <0.05). Thirteen patients received subsequent therapy after ibrutinib discontinuation with idelalisib (n=3), lenalidomide (n=3), rituximab with bendamustine (n=2), R-CHOP (n=2), or other treatments (n=3). ORR to post ibrutinib therapy was 23.1% with CR in 3/13 patients (reason for discontinuation- RT - 1, other reasons- 2). Two patients had SD (both discontinued Ibrutinib for PD) leading to a CBR of 38.5%. Eight of 13 patients had PD and died during follow up period. Conclusion: Ibrutinib has good efficacy in the treatment of CLL as front-line therapy and in relapse refractory disease in a real-world setting. However, patients who discontinue therapy have poor survival outcomes and poor response to salvage therapy. DisclosuresNo relevant conflicts of interest to declare.

Body composition measurements and overall survival in patients with resectable pancreatic adenocarcinoma receiving neoadjuvant chemotherapy: Analysis from SWOG S1505.

4131 Background: Sarcopenia and sarcopenic obesity have been associated with overall survival (OS) in patients (pts) with borderline resectable and advanced pancreatic ductal adenocarcinoma (PDA), but little is known about the effect of body composition on OS in pts with resectable PDA. We examined the relationship between skeletal muscle and adipose tissue measurements on baseline computed tomography (CT) and OS of pts with resectable PDA in a secondary analysis of SWOG S1505 (NCT02562716). Methods: SWOG S1505 enrolled pts with resectable PDA who were randomized to receive neoadjuvant FOLFIRINOX or gemcitabine-nab paclitaxel, followed by surgical resection. Baseline axial CT images at the L3 level were analyzed with externally validated software and measurements were recorded for skeletal muscle area (SMA), density (SMD) and index (SMI); visceral adipose tissue area (VATA) and density (VATD); and subcutaneous adipose tissue area (SATA) and density (SATD). Sarcopenia was defined as SMI &lt; 52 cm2/m2 for men and &lt; 39 cm2/m2 for women; sarcopenic obesity was defined as sarcopenia and a body mass index (BMI) &gt;30 kg/m2. The relationships between CT metrics and OS were analyzed using Cox regression models, with 95% CI. Statistical significance was defined as p &lt; 0.05. Results: Of 98 pts with available baseline abdominal CT, 8 were excluded for scan quality, resulting in 90 evaluable cases: 51 men (57%), 39 women (43%); mean age, 63.2 years, SD 8.5; mean BMI, 29.3 kg/m2, SD 6.4; 80 (89%) White, 6 (7%) Black, and 4 (4%) unknown. Sarcopenia was present in 32 (36%) and sarcopenic obesity in 10 (11%) patients. Univariable analyses for the variables of interest indicated VATA (HR 1.24; 0.97-1.60; p = 0.09) and SMD (HR 0.75; 0.57-0.98; p = 0.04) were associated with OS. Analyses adjusted for sex, race, age, BMI, performance score, contrast use, sarcopenia, and sarcopenic obesity showed VATA was associated with OS (HR 1.58; 1.0-2.51; p = 0.05). No significant difference in median OS was observed between pts with vs. without sarcopenia (OS 23.6 [19.3-NA] vs. 27.9 months [18.6-NA], respectively). Pts with vs. without sarcopenic obesity had lower median OS: 18.6 (14.7-NA) vs. 25.1 (10.5-46.0) months, respectively, but this difference was not statistically significant (HR 1.90, 95%CI 0.81-4.47, p = 0.14). Conclusions: This is one of the first studies to systematically evaluate body composition parameters in a prospective trial of patients with resectable PDA who received neoadjuvant chemotherapy. We found that visceral fat (VATA) is a prognostic marker in this population, but that sarcopenia may not be predictive in early PDA. Further studies to define the impact of longitudinal changes in body composition on individual outcomes may provide greater precision in predicting OS for subsets of pts with pancreatic cancer. Clinical trial information: NCT02562716.

Impact of the COVID-19 pandemic on care delivery and outcomes for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).

4137 Background: The coronavirus disease 2019 (COVID-19) pandemic has caused abrupt changes to the US health system and disruption in cancer care delivery. Little has been reported on the impact of COVID-19 on patients with mPDAC and the care delivery. Our study aimed to characterize the impact of COVID-19 on healthcare utilization and outcomes for patients with mPDAC in the US in the community oncology setting. Methods: We performed a retrospective cohort study of adult patients diagnosed with mPDAC between March – September 2019 and March – September 2020 using the nationwide Flatiron Health EHR database, comprising data from over 280 (largely community based) cancer clinics. Patients were stratified into two cohorts based on the year of diagnosis (2019 vs. 2020). Clinical characteristics were summarized including age at metastatic diagnosis, stage at initial diagnosis, and ECOG performance score (PS). Overall survival (OS) from metastatic diagnosis was estimated using Kaplan-Meier methods. A sensitivity analysis limiting the follow-up time to November of each year was conducted. Results: Overall, 1,719 patients were included in the study (2019: n = 923, 2020: n = 796); both cohorts had similar demographic compositions in terms of age and sex (2019: median age = 70 (IQR: 62 – 76), 52.2% male; 2020: median age = 70 [IQR: 62 – 76], 53.5% male). In 2020, the number of newly diagnosed mPDAC patients decreased by 13.8% compared to 2019. A slightly higher proportion of patients were initially diagnosed with stage IV disease in 2020 (69.7%) vs 2019 (62.3%). A similar proportion of patients with ECOG PS 0-1 was observed between the two cohorts (2019: 48.5%; 2020: 47.9%). The number of visits recorded within the first 90 days after metastatic diagnosis was similar between the two cohorts (2019: median 8 [IQR: 3 – 14]; 2020: median 9 [IQR: 4 – 14]). For both cohorts, the proportion of patients who received 1L treatment was similar (2019: 75.8%; 2020: 76.5%), and the most common 1L treatment regimen was gemcitabine plus nab-paclitaxel (2019: 37.6%; 2020: 40.9%). Of the 1L treated populations, 37.6% of patients diagnosed in 2019 received second line (2L) compared to 17.9% of the 2020 cohort; 16.9% of 1L treated patients in 2019 received 2L in the sensitivity analysis. Patients diagnosed in 2020 had a significantly lower median OS of 6.1 months (95% CI: 5.4 – 6.9) compared to patients diagnosed in 2019: 8.4 months (7.5 – 9.0) (p &lt; 0.001). Conclusions: During the COVID-19 pandemic era, the diagnoses of de novo mPDAC appears to have been impacted, with a higher number of patients diagnosed with advanced stage at presentation. Our analysis suggests that while patients diagnosed in 2020 received a similar level of care as those in 2019, their survival outcomes were adversely affected. Further research is necessary to characterize the impact of the COVID-19 pandemic on cancer care and outcomes.