Survival In Pancreatic Cancer Research Articles

Mutation-site localized non-B DNA burden and survival heterogeneity in early-stage pancreatic cancer.

4166 Background: Pancreatic cancer is a highly aggressive disease with a poor prognosis, and one in which most measure of genomic instability (e.g., tumor mutation burden (TMB), fraction of genome altered (FGA)) have thus far, not proven informative in differentiating survival. Non-B DNA are alternative DNA forms that deviate from the canonical B-DNA structure with potential to increase susceptibility to mutations, leading to the development of cancer. The role of non-B in pancreatic cancer has not been fully explored. Herein, we investigate the relationship between gene mutation sites co-localized with non-B DNA motifs in terms of survival and B-DNA features. Methods: Using TCGA data, we derived a genome-wide mutation signature on 104 early-stage pancreatic patients. We introduced a metric, mutation-localized non-B burden (MLNB) by the number of non-b motifs containing mutation sites, normalized to the number of mutations and motif library size. We applied MLNB to patient-specific mutation signatures to derive an MLNB burden for non-B DNA structure motifs: G-quadruplexes (G4), Z-DNA, inverted repeats (IR), mirror repeats (MR), direct repeats (DR), and short tandem repeats (STR). We performed a cluster analysis on MLNB and compared groups based on overall survival (OS) in months (mos) using a log-rank test. Comparisons of B-DNA-derived molecular features among clusters were performed using a Kruskal-Wallis and Fisher Exact test. Results: Among the 104 early-stage pancreatic patients with a mutation signature, MLNB clustering resulted in six patient clusters that differentiated by non-B DNA structure, with DR burden the longest OS cluster (n=23, median OS=30mos), significantly (p < 0.05) differing as compared to IR (n=23, median OS=15 mos), STR (n=20, median OS=16mos), MR with lack of IR (n=14, median OS=13mos) and MR with IR (n=16, median OS=8mos). A mix of Z-DNA and G4 burden defined a cluster with shorter OS (n=22, median OS=14mos) as compared to DR, though not significant. Patients with the longest OS, MLNB-DR burden cluster had mutation signatures enriched in MAPK and Notch signaling pathways, as compared to the other clusters enriched with double-stranded break and mismatch repair (IR), hedgehog and WNT signaling (STR), and interleukin-4 signaling (MR) pathways. Among all clusters, CDKN2A deletion was most prevalent except for MLNB-DR burden cluster. No Significant differences were found between the MLNB clusters with age, race gender, KRAS and TP53 mutations, FGA, TMB, tumor purity, Bailey and Moffit subtypes. Conclusions: Our results point towards the potential use of MLNB as an emerging marker of site-structure genomic instability. Considering that triplex DNA is emerging as a marker genomic instability, and that we distinguish between two MR groups based on IR burden, our results may provide insights into various instability mechanisms associated with poor survival in pancreatic cancer.

The genomic, transcriptomic, and immunological landscape of TROP2 in solid tumors.

3118 Background: TROP2 expression is associated with decreased overall survival in colorectal and pancreatic cancers. The antibody drug conjugate sacituzumab delivers a SN38 toxic payload to TROP2-expressing cells and is approved for the treatment of breast cancer and urothelial carcinoma. We aimed to explore the genomic and immunological landscape of TACSTD2 (TROP2-encoding gene) in different solid tumors. Methods: Tumors from breast cancer (BC, N=11,246), colorectal carcinoma (CRC, N= 15,425), liver cancer (LC, N=433), pancreatic cancer (PC, N=5,488) and urothelial carcinoma (UC, N=5,488) were assessed at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing of DNA (592-gene or whole exome) and RNA (whole transcriptome). PD-L1 (SP142; Positive (+): ≥2+, ≥5%) expression was assessed by IHC. When investigating the genomic landscape, mutation prevalence was calculated for pathogenic SNVs/indels. TACSTD2-High (H) and -Low (L) expression was defined as top and bottom quartile of TACSTD2 transcripts per million, respectively. A transcriptomic signature predictive of response to immunotherapy was applied (T cell-inflamed score [Bao, 2020]). tests were applied as appropriate, with P-values adjusted for multiple comparisons ( p < .05). Real-world overall survival data was obtained from insurance claims and Kaplan-Meier estimates were calculated for molecularly defined subpopulations of patients. Results: Compared to TACSTD2-L, TACSTD2-H tumors had a higher prevalence of TP53 mutations in BC ( TACSTD2-H 59% vs -L 48%), CRC (77% vs 71%), LC (43% vs 23%) and PC (83% vs 69%), whereas UC TACSTD2-H had a lower prevalence (54% vs 67%, p < .05 for all). TACSTD2-H tumors had a higher rate of KRAS mutations in CRC (55% vs 38%, p < .05) and PC (96% vs 78%, p < .05). In CRC, the percentage of KRAS mutations that were G12C was higher in TACSTD2-H (7.3% vs 6.4%, p < .05). TACSTD2-H tumors had a higher rate of ARID1A mutations in CRC (6.7% vs 10%, p < .05) and UC (29 vs 20%, p < .05). A higher prevalence of PD-L1+ tumors was observed in CRC TACSTD2-H (6.4 vs 3.9%, p < .05) and the opposite pattern was observed in UC (16% vs 37%, p < .05). TACSTD2-H tumors were more frequently T cell-inflamed across investigated cancers (BC: TACSTD2-H 36% vs -L 19%, CRC: 29% vs 14%, LC: 54% vs 10%, PC: 42% vs 20%, UC: 32% vs 28%, all p < .05). TACSTD2-H was associated with worse overall survival in PC (HR 1.31 [1.19-1.44], p < .001), BC (HR 1.13 [1.03-1.23], p < .007) and CRC (HR 1.33 [1.24-1.42], p < .001), while this association was not observed in UC (HR .98 [.86-1.12], p = .75) or LC (HR 1.14[.82-1.57], p = .44). Conclusions: The association of TACSTD2 expression with KRAS, TP53 and ARID1A mutations and T cell-inflamed tumors (ICI responsive) should be considered as possible combination therapies with TROP2 targeting antibody drug conjugates are investigated.

P-370 The role of Ca 19-9 in progression, recurrence and survival of borderline resectable pancreatic cancer

P-370 The role of Ca 19-9 in progression, recurrence and survival of borderline resectable pancreatic cancer

Real-world impact of time-to-treatment initiation and initial treatment modality on survival in pancreatic and colorectal cancers.

e15646 Background: Overall survival for patients with pancreatic ductal adenocarcinoma (PDAC) and colorectal cancers (CRC) has increased significantly over the past decade; however, the optimal time-to-treatment initiation (TTI) and initial treatment modality (ITM) have not been defined. These variables have likely been affected by increased adoption and changes in types of neoadjuvant treatment strategies for these cancer types. Thus, we performed a retrospective observational study of TTI and ITM in patients with CRC and PDAC within the MHealth/Fairview medical system. Methods: We identified 424 patients with stage I-III RC and 316 patients with stage I-III PDAC within the MHealth/Fairview system (Minneapolis, MN) from 2011-2021 with North American Association of Central Cancer Registries data enriched by the electronic health record. Patients were stratified by TTI from diagnoses as: 0-7 days, 8-14 days, 15-28 days, 29-42 days, and over 43 days. ITM, defined as initial chemotherapy/chemoradiation, surgery, or radiation, was analyzed independently for patients with rectal cancer (N = 267) and PDAC. Effect of TTI and ITM on overall survival was calculated using a Cox proportional Hazard (CPH) model controlling for clinical stage. Results: TTI was significantly associated with survival in CRC, with patients treated in 8-14 days and 15-28 days showing increased survival over patients treated in over 43 days (HR 0.397, p = 0.007 and HR 0.276 p < 0.001, respectively). There was no significant hazard for TTI and survival in PDAC. We also found that neoadjuvant chemotherapy/chemoradiation had a lower hazard for death in rectal cancer relative to upfront surgery (HR 0.323, p = 0.002), when controlling for stage. Surgery was significantly more likely to be correlated with stage I or II disease than chemotherapy/chemoradiation (68.5% vs 24.7%, p < 0.0001 by Spearman method). There was no significant association between ITM and survival in patients with PDAC. Conclusions: Early treatment for CRC is associated with improved survival in this population, implying that treatment delays decrease the efficacy of curative-intent therapy. Evaluation of treatment modality in the rectal sub-group showed improved outcomes with neoadjuvant chemotherapy and chemoradiation, despite upfront surgery being associated with lower stage. The lack of association between TTI and survival in PDAC is likely related to the relatively poor outcomes observed with this disease and highlights the need for better screening and treatment for resectable disease. These results are notable because they suggest that a thorough workup and appropriate therapy may be more important than rapid treatment.

Trends in treatment patterns and survival outcomes in pancreatic cancer: A nationwide population-based study in Korea

BackgroundThe treatment of pancreatic cancer has evolved; however, real-world data on treatment trends remain scarce. This study investigated treatment patterns for pancreatic cancer and patient survival using a nationwide population-based study in Korea. MethodsUsing the National Health Insurance database, data from 78,920 patients diagnosed with pancreatic cancer in Korea between 2006 and 2019 were extracted. Treatment patterns and survival by age group and year of diagnosis were examined. ResultsPrimary treatment was delivered as follows: 16,562 patients (21.0%) underwent surgery, 20,998 patients (26.6%) received chemotherapy, 1332 patients (1.7%) received chemoradiotherapy, and 40,040 patients (50.7%) received supportive care only. The proportion of patients undergoing surgery or chemotherapy increased gradually in all age groups over time. The commonly used anti-cancer drugs have changed from gemcitabine±erlotinib to gemcitabine+nab-paclitaxel and FOLFIRINOX. Survival improved mainly in patients who underwent surgery or chemotherapy. Median overall survival for all patients improved from 5.5 months in 2006–2008 to 9.8 months in 2018–2019, with greater improvement observed in younger age groups: 8.8–18.8 months, age ≤59 years, 6.8–14.6 months, age 60–69 years, 4.2–8.3 months, age 70–79 years and 2.4–3.4 months, age ≥80 years (all p < 0.0001). ConclusionsAn increase in the rates of surgery and chemotherapy for pancreatic cancer was observed. Survival rates for pancreatic cancer have generally improved over the past decade and are greater in patients undergoing surgery or chemotherapy and in younger age groups.

Factors associated with failure to operate and its impact on survival in early-stage pancreatic cancer.

Curative intent for localized pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) requires surgery, but despite improved perioperative outcomes, surgery remains underutilized. This study analyzed the Texas Cancer Registry (TCR) to identify resectable PDAC patients who underwent curative-intent surgery in Texas between 2004 and 2018. We then evaluated demographic and clinical factors associated with failure to operate and survival (OS). We identified patients with localized PDAC or regional lymph node spread between 2004 and 2018 in the TCR. Resection rates were determined and multivariable regression and cox proportional hazards were used to identify factors associated with failure to OS. Of 4274 patients, 22% underwent resection, 57% were not offered surgery, 6% had comorbidities precluding surgery, and 3% refused. Resection rates decreased from 31% in 2004 to 22% in 2018. Increasing age was associated with failure to operate (odds ratio [OR] 2.55; 95% confidence interval [CI] 1.80-3.61; p < 0.0001) while treatment at a Commission on Cancer (CoC) center correlated with reduced failure to operate (OR 0.63; 95% CI 0.50-0.78; p < 0.0001). Resection correlated with survival (HR 0.34; 95% CI 0.31-0.38; p < 0.0001) as did treatment at a National Cancer Institute (NCI)-designated center (hazard ratio 0.79; 95% CI 0.70-0.89; p < 0.0001). Surgery is underutilized for the treatment of resectable PDAC in Texas with decreasing utilization, annually. Evaluation at CoC was associated with improved resection rates and NCI was associated with increased survival. Expanding access to multidisciplinary care including trained hepato-pancreatico-biliary surgeons may improve outcomes for PDAC patients.

Association of rurality, socioeconomic status, and race with pancreatic cancer surgical treatment and survival.

Pancreatectomy is a necessary component of curative intent therapy for pancreatic cancer, and patients living in nonmetropolitan areas may face barriers to accessing timely surgical care. We evaluated the intersecting associations of rurality, socioeconomic status (SES), and race on treatment and outcomes of Medicare beneficiaries with pancreatic cancer. We conducted a retrospective cohort study, using fee-for-service Medicare claims of beneficiaries with incident pancreatic cancer (2016-2018). We categorized beneficiary place of residence as metropolitan, micropolitan, or rural. Measures of SES were Medicare-Medicaid dual eligibility and the Area Deprivation Index. Primary study outcomes were receipt of pancreatectomy and 1-year mortality. Exposure-outcome associations were assessed with competing risks and logistic regression. We identified 45 915 beneficiaries with pancreatic cancer, including 78.4%, 10.9%, and 10.7% residing in metropolitan, micropolitan, and rural areas, respectively. In analyses adjusted for age, sex, comorbidity, and metastasis, residents of micropolitan and rural areas were less likely to undergo pancreatectomy (adjusted subdistribution hazard ratio = 0.88 for rural, 95% confidence interval [CI] = 0.81 to 0.95) and had higher 1-year mortality (adjusted odds ratio = 1.25 for rural, 95% CI = 1.17 to 1.33) compared with metropolitan residents. Adjustment for measures of SES attenuated the association of nonmetropolitan residence with mortality, and there was no statistically significant association of rurality with pancreatectomy after adjustment. Black beneficiaries had lower likelihood of pancreatectomy than White, non-Hispanic beneficiaries (subdistribution hazard ratio = 0.80, 95% CI = 0.72 to 0.89, adjusted for SES). One-year mortality in metropolitan areas was higher for Black beneficiaries (adjusted odds ratio = 1.15, 95% CI = 1.05 to 1.26). Rurality, socioeconomic deprivation, and race have complex interrelationships and are associated with disparities in pancreatic cancer treatment and outcomes.

Pathologic Tumor Regression is Associated With Improved Survival in Pancreatic Cancer.

The advent of effective chemotherapy regimens has increased the use of neoadjuvant multiagent chemotherapy in pancreatic cancer. However, the effect of tumor downstaging with neoadjuvant treatment on survival is unclear. Retrospective study included all resected patients with pancreatic adenocarcinoma who underwent neoadjuvant chemotherapy with FOLFIRINOX or gemcitabine/Abraxane. Downstaging was quantified using (1) difference between presenting AJCC clinical and final pathologic stage and (2) College of American Pathologists (CAP) Tumor Regression Grading Schema. Eighty-seven patients met inclusion criteria. FOLFIRINOX was the most common regimen, 63.2% vs 21.8%. Change in regimen occurred in 15% of patients. Downstaging based on a difference in AJCC stage group occurred in only 4.6%. In contrast, 45.2% were classified as downstaged by the CAP Tumor Regression of 0-2. Downstaging was similar for FOLFIRINOX gemcitabine/Abraxane (64.7 vs 53.6, P = .12) using the CAP criteria. On univariate analysis, treatment regimen (gemcitabine/Abraxane vs FOLFIRINOX, median survival 27 vs 29 mo; HR 1.57, P = .2) had similar survival. Downstaging by the AJCC stage was not associated with improved survival (HR 1.51, P = .4). However, there was a survival benefit for those downstaged by the CAP Tumor Regression Grading Schema, the median survival of 41 mo vs 25 mo; HR 3.05, P = .009. Improved survival 3.32 (1.35-8.16), P = .009) was maintained on multivariate analysis. Survival is significantly improved in those downstaged, as assessed by the CAP Tumor Regression Schema. Downstaging is an important prognostic variable that can help with joint decision making for clinicians and patients.

Prediction of risk and overall survival of pancreatic cancer from blood soluble immune checkpoint-related proteins.

Immune checkpoint inhibition holds promise as a novel treatment for pancreatic ductal adenocarcinoma (PDAC). The clinical significance of soluble immune checkpoint (ICK) related proteins have not yet fully explored in PDAC. We comprehensively profiled 14 soluble ICK-related proteins in plasma in 70 PDAC patients and 70 matched healthy controls. Epidemiological data of all subjects were obtained through structured interviews, and patients' clinical data were retrieved from electronical health records. We evaluated the associations between the biomarkers with the risk of PDAC using unconditional multivariate logistic regression. Consensus clustering (k-means algorithm) with significant biomarkers was performed to identify immune subtypes in PDAC patients. Prediction models for overall survival (OS) in PDAC patients were developed using multivariate Cox proportional hazards regression. Harrell's concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve and calibration curve were utilized to evaluate performance of prediction models. Gene expressions of the identified ICK-related proteins in tumors from TCGA were analyzed to provide insight into underlying mechanisms. Soluble BTLA, CD28, CD137, GITR and LAG-3 were significantly upregulated in PDAC patients (all q < 0.05), and elevation of each of them was correlated with PDAC increased risk (all p < 0.05). PDAC patients were classified into soluble immune-high and soluble immune-low subtypes, using these 5 biomarkers. Patients in soluble immune-high subtype had significantly poorer OS than those in soluble immune-low subtype (log-rank p = 9.7E-03). The model with clinical variables and soluble immune subtypes had excellent predictive power (C-index = 0.809) for the OS of PDAC patients. Furthermore, the immune subtypes identified with corresponding genes' expression in PDAC tumor samples in TCGA showed an opposite correlation with OS to that of immune subtypes based on blood soluble ICK-related proteins (log-rank p =0.02). The immune-high subtype tumors displayed higher cytolytic activity (CYT) score than immune-low subtype tumors (p < 2E-16). Five soluble ICK-related proteins were identified to be significantly associated with the risk and prognosis of PDAC. Patients who were classified as soluble immune-low subtype based on these biomarkers had better overall survival than those of the soluble immune-high subtype.

Gene signature developed for predicting early relapse and survival in early-stage pancreatic cancer.

The aim of this study was to construct a predictive signature integrating tumour-mutation- and copy-number-variation-associated features using machine learning to precisely predict early relapse and survival in patients with resected stage I-II pancreatic ductal adenocarcinoma. Patients with microscopically confirmed stage I-II pancreatic ductal adenocarcinoma undergoing R0 resection at the Chinese PLA General Hospital between March 2015 and December 2016 were enrolled. Whole exosome sequencing was performed, and genes with different mutation or copy number variation statuses between patients with and without relapse within 1 year were identified using bioinformatics analysis. A support vector machine was used to evaluate the importance of the differential gene features and to develop a signature. Signature validation was performed in an independent cohort. The associations of the support vector machine signature and single gene features with disease-free survival and overall survival were assessed. Biological functions of integrated genes were further analysed. Overall, 30 and 40 patients were included in the training and validation cohorts, respectively. Some 11 genes with differential patterns were first identified; using a support vector machine, four features (mutations of DNAH9, TP53, and TUBGCP6, and copy number variation of TMEM132E) were further selected and integrated to construct a predictive signature (the support vector machine classifier). In the training cohort, the 1-year disease-free survival rates were 88 per cent (95 per cent c.i. 73 to 100) and 7 per cent (95 per cent c.i. 1 to 47) in the low-support vector machine subgroup and the high-support vector machine subgroup respectively (P < 0.001). Multivariable analyses showed that high support vector machine was significantly and independently associated with both worse overall survival (HR 29.20 (95 per cent c.i. 4.48 to 190.21); P < 0.001) and disease-free survival (HR 72.04 (95 per cent c.i. 6.74 to 769.96); P < 0.001). The area under the curve of the support vector machine signature for 1-year disease-free survival (0.900) was significantly larger than the area under the curve values of the mutations of DNAH9 (0.733; P = 0.039), TP53 (0.767; P = 0.024), and TUBGCP6 (0.733; P = 0.023), the copy number variation of TMEM132E (0.700; P = 0.014), TNM stage (0.567; P = 0.002), and differentiation grade (0.633; P = 0.005), suggesting higher predictive accuracy for prognosis. The value of the signature was further validated in the validation cohort. The four genes included in the support vector machine signature (DNAH9, TUBGCP6, and TMEM132E were novel in pancreatic ductal adenocarcinoma) were significantly associated with the tumour immune microenvironment, G protein-coupled receptor binding and signalling, cell-cell adhesion, etc. The newly constructed support vector machine signature precisely and powerfully predicted relapse and survival in patients with stage I-II pancreatic ductal adenocarcinoma after R0 resection.

Prognostic Role of Geriatric Nutritional Risk Index in Patients with Pancreatic Cancer: A Meta-Analysis

Background: The Geriatric Nutritional Risk Index (GNRI) is used to assess the prognosis of patients with pancreatic cancer. Therefore, this meta-analysis was conducted to evaluate the association between the GNRI and prognosis in pancreatic cancer. Methods: We performed a pooled analysis of the hazard ratios (HRs) and 95% confidence intervals (CIs) of the GNRI for survival in pancreatic cancer. Using pooled odds ratios (ORs) and 95% CIs, we investigated the association between the GNRI and clinicopathological characteristics of pancreatic cancer. Results: Six studies were included in this meta-analysis, totaling 1,513 patients. A low GNRI was significantly associated with a poorer overall survival (OS) in the pooled results (HR, 1.95; 95% CI, 1.29–2.94; p = 0.002) in pancreatic cancer. However, GNRI was not significantly associated with progression-free survival (PFS) in pancreatic cancer (HR, 1.57; 95% CI, 0.90–2.73; p = 0.114). The pooled results indicated that a low GNRI was significantly associated with tumor location of pancreas head (OR, 2.18; 95% CI, 1.45–3.29; p < 0.001). Conclusions: This meta-analysis showed that low GNRI was significantly associated with poor OS but not with poor PFS in patients with pancreatic cancer. The GNRI is a novel and effective risk factor and a potential biomarker for the prognosis of pancreatic cancer.

Exploration and Validation of Pancreatic Cancer Hub Genes Based on Weighted Gene Co-Expression Network Analysis and Immune Infiltration Score Analysis.

To find pancreatic cancer (PC)-related hub genes based on weighted gene co-expression network analysis (WGCNA) construction and immune infiltration score analysis and validate them immunohistochemically by clinical cases, to generate new concepts or therapeutic targets for the early diagnosis and treatment of PC. In this study, WGCNA and immune infiltration score were utilized to identify the relevant core modules of PC and the hub genes within these core modules. Using WGCNA analysis, data from PC and normal pancreas integrated with TCGA and GTEX were analyzed and brown modules were chosen from the six modules. Five hub genes, including DPYD, FXYD6, MAP6, FAM110B, and ANK2, were discovered to have differential survival significance via validation tests utilizing survival analysis curves and the GEPIA database. The DPYD gene was the only gene associated with PC survival side effects. Validation of the Human Protein Atlas (HPA) database and immunohistochemical testing of clinical samples showed positive results for DPYD expression in PC. In this study, we identified DPYD, FXYD6, MAP6, FAM110B, and ANK2, as immune-related candidate markers for PC. Only the DPYD gene had a negative impact on the survival of PC patients. Through validation of the HPA database and immunohistochemical testing of clinical cases, we believe that the DPYD gene brings novel ideas and therapeutic targets in the diagnosis and treatment of PC.

Management, Survival, and Costs of Pancreatic Cancer: Population-Based Observational Study in Catalonia

Few published studies comprehensively describe the characteristics of patients with pancreatic cancer and their treatment in clinical practice. This study aimed to describe the current clinical practice for treating pancreatic cancer in Catalonia, along with the associated survival and treatment costs. A retrospective observational cohort study in patients diagnosed with pancreatic cancer from 2014 to 2018, using data from the healthcare records of the Public Health System of Catalonia, was conducted. Treatment patterns and costs were described by age groups from 2014 to 2018, with survival reported until December 2021. The proportion of patients receiving surgery with curative intent was low, especially in older patients (23% of patients <60 years and 9% of patients ≥80 years). The percentage of patients treated with drugs for unresectable disease also decreased with age (45% of patients <60 years and 8% of patients ≥80 years). Although age was associated with significant differences in survival after curative surgery, no differences attributable to age were observed in patients who received pharmacological treatment for unresectable disease. In patients under 60 years of age, the mean cost of the first year of treatment was EUR 17,730 (standard deviation [SD] 5754) in those receiving surgery and EUR 5398 (SD 9581) in those on pharmacological treatment for unresectable disease. In patients over 80, the mean costs were EUR 15,339 (SD 2634) and EUR 1845 (SD 3413), respectively. Half of the patients diagnosed with pancreatic cancer did not receive specific treatment. Surgery with curative intent was associated with longer survival, but only 18% of (mostly younger) patients received this treatment. Chemotherapy was also used less frequently in patients of advanced age, though survival in treated patients was comparable across all age groups, so careful oncogeriatric assessment is advisable to ensure the most appropriate indication for eligibility in older patients. In general, earlier diagnosis and more effective pharmacological treatments are necessary to treat frail patients with high comorbidity, a common profile in older patients.

ASO Visual Abstract: Hospital Designations and Their Impact on Guideline-Concordant Care and Survival in Pancreatic Cancer: Do They Matter?

ASO Visual Abstract: Hospital Designations and Their Impact on Guideline-Concordant Care and Survival in Pancreatic Cancer: Do They Matter?

The Revised R Status is an Independent Predictor of Postresection Survival in Pancreatic Cancer After Neoadjuvant Treatment.

To investigate the oncological outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) who had an R 0 or R 1 resection based on the revised R status (1mm) after neoadjuvant therapy (NAT). The revised R status is an independent prognostic factor in upfront-resected PDAC; however, the significance of 1mm margin clearance after NAT remains controversial. Patients undergoing pancreatectomy after NAT for PDAC were identified from 2 prospectively maintained databases. Clinicopathological and survival data were analyzed. The primary outcomes were overall survival (OS), recurrence-free survival (RFS), and pattern of recurrence in association with R 0 >1mm and R 1 ≤1mm resections. Three hundred fifty-seven patients with PDAC were included after NAT and subsequent pancreatic resection. Two hundred eight patients (58.3%) received FOLFIRINOX, 41 patients (11.5%) received gemcitabine-based regimens, and 299 individuals (83.8%) received additional radiotherapy. R 0 resections were achieved in 272 patients (76.2%) and 85 patients (23.8%) had R 1 resections. Median OS after R 0 was 41.0 months, compared with 20.6 months after R 1 resection ( P = 0.002), and even longer after additional adjuvant chemotherapy ( R 0 44.8 vs R1 20.1 months; P = 0.0032). Median RFS in the R 0 subgroup was 17.5 months versus 9.4 months in the R 1 subgroup ( P < 0.0001). R status was confirmed as an independent predictor for OS ( R 1 hazard ratio: 1.56, 95% CI: 1.07-2.26) and RFS ( R 1 hazard ratio: 1.52; 95% CI: 1.14-2.0). In addition, R 1 resections were significantly associated with local but not distant recurrence ( P < 0.0005). The revised R status is an independent predictor of postresection survival and local recurrence in PDAC after NAT. Achieving R 0 resection with a margin of at least 1mm should be a primary goal in the surgical treatment of PDAC after NAT.

Naples prognostic score may predict overall survival in metastatic pancreatic cancer.

Naples prognostic score (NPS) based on nutritional and inflammatory parameters can predict response to chemotherapy and overall survival (OS) in many cancer types. However, its significance in metastatic pancreatic cancer (PC) remains unclear. We evaluated the prognostic significance of the NPS in patients with metastatic PC receiving first line chemotherapy. We retrospectively analyzed 215 patients with metastatic PC receiving first line FOLFIRINOX chemotherapy. NPS's were calculated using pre-chemotherapy laboratory data. Patients were divided into three groups according to their scores (NPS: 0; 1 & 2; 3 & 4 were grouped as 1, 2 and 3, respectively). The association of NPS with clinicopathological features and OS were evaluated. Median age was 64 years, and median OS was 10.5 months. Hemoglobin levels were lower and Ca-19-9 values were higher with increasing NPS. Frequency of patients with bone and/or liver metastases, and with greater than 5 metastatic focus were higher in group 3. A lower NPS was associated with longer OS. The median OS in groups 1, 2, and 3 were 19.5, 12, and 8 months, respectively, and differed significantly. Univariate analysis revealed effect of NPS (3-4) on OS (HR: 2.38, 1.77-3.19). Other prognostic factors affecting OS were age, ECOG, liver, bone or lymph node metastases, number of metastatic foci (<5 vs >5), de-novo metastatic disease, and serum Ca-19-9 levels. NPS (3-4) was identified as an independent prognostic factor negatively affecting OS (HR: 1.89, 1.34-2.65) in multivariate analysis. NPS may be a useful prognostic marker for the prediction of OS in metastatic PC patients receiving systemic chemotherapy.

Abstract 5918: Interrogating host-intratumoral microbial interactions in pancreatic cancer

Abstract Cancer is increasingly becoming a rising cause of mortality worldwide. Microbiota, both within the gut and tumors, has emerged as a significant player influencing tumor growth and responses to therapies. The tumor niche provides a privileged microenvironment for microbial colonization. Recent evidence links microbiota and pancreatic tumorigenesis. Pancreatic ductal adenocarcinoma (PDAC), is an aggressive cancer surrounded by a highly immuno-suppressive tumor microenvironment (TME) which limits efficacy of most available therapies. We have previously reported that rare long-term survival in pancreatic cancer is associated with an intratumoral microbial signature which correlates with enhanced TME immunoactivation, suggestive of microbial mediated immune cell recruitment. A gut-to-tumor microbial crosstalk was also found in a human-to-mouse Fecal Microbiota Transplant (FMT) tumor model. While we have identified the vital role of microbiota in affecting tumor immunity, there is still a gap of knowledge about local microbial interactions within TME. Deeper understanding of the microbial mediated events that are triggered and follow PDAC development, which act to induce and support tumor growth, would provide us with potential novel targets that could be blocked to reverse PDAC immunosuppression and tumor growth. To interrogate the features of the pancreatic tumor microbial niche, we performed spatial co-detection of microbial and host targets to identify the cellular compartment which interacts with microbes inside the TME in clinical samples. We developed novel qualitative and quantitative imaging methodologies for evaluating crosstalk between the host and microbes. We also evaluated the effect of microbial burden on transcriptomic changes in host cells through multiple spatial sequencing approaches. Overall, we dissect the functional role of microbes in orchestrating TME organization and their effect on tumor signaling. Citation Format: Vidhi Chandra, Hajar Rajaei, Seyda Baydogan, Javier Gomez, Sammy Ferri-Borgogno, Anirban Maitra, Erick Riquelme, Ismet Sahin, Jared Burks, Michael Kim, Florencia McAllister. Interrogating host-intratumoral microbial interactions in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5918.

Abstract 1914: Pancreatic cancer and racial disparity in Hampton Roads

Abstract Background: Pancreatic cancer is one of the most lethal diseases, with a dismal five-year survival rate of 9% and a median post-diagnosis survival of 6 months. It is currently the third leading cause of cancer-related death in the United States. The dismal prognosis of patients diagnosed with pancreatic cancer points to our limited arsenal of effective anticancer therapies and screening tools. Pancreatic cancer disproportionately affects the Black and Jewish populations; nationally we see lower survival and later stage at diagnosis among the black population when compared to their white counterparts. Objectives: This study aims to measure racial disparity in overall survival, diagnosis, and treatment regimens of pancreatic cancer in Hampton Roads Virginia in comparison to the national average. We hope to highlight the similarities/differences of cancer disparity in the two major racial groups in our local Pancreatic Ductal Adenocarcinoma (PDAC) cohort. Methods: This retrospective study uses a cohort of 640 patients diagnosed with pancreatic cancer between 2008 and 2016 within the Sentara Healthcare and/or Virginia Oncology Associates (VOA) system in Hampton Roads. The cohort was stratified into two groups: 191 patients diagnosed with operable disease who underwent surgical resection, and 449 patients diagnosed with inoperable disease; and then further separated into a white and black populations. Survival was calculated from date of initial diagnosis to date of last follow-up or death from all-cause mortality. Clinical and pathological parameters (TNM classification) and standard treatment modalities were reviewed, validated, and compared using electronic medical records at Sentara EPIC and VOA iKnow Medicine. Results: Of the 191 pancreatic cancer patients, 45 underwent surgical resection only, 100 received surgery and adjuvant chemotherapy, and 46 received NACT and surgery. In the operable cohort, 41.5% of the PDAC patients are African American (AA) and 55.8% are Caucasians. Thus, pancreatic cancer incidence among black patients was over-represented in Hampton Roads Virginia that has a 31.3% AA population. Treatment provided and stage of diagnosis for pancreatic cancer are comparable in the two major race groups. The total length of survival of our black patients was not worse when compared to the white patients in both operable and inoperable cohorts, however white patients more frequently met the 5-year survival milestone. Conclusion: Our PDAC patients of the two race groups still have a lower 5-year survival as compared to that of the national average (SEER data). The underlying factors contributing to the dismal 5-year survival rate and higher incidence are likely multifactorial, possibly explained by unhealthy diet, genetic factors, mutant carriers, social economic status, insurance, and increased risk behaviors as compared to national averages. Citation Format: Zakary L. Kolkey. Pancreatic cancer and racial disparity in Hampton Roads [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1914.

NcRNA-mediated upregulation of FAM83A is associated with poor prognosis and immune infiltration in pancreatic cancer.

Malignant pancreatic cancer has poor long-term survival. Increasing evidence shows that FAM83A (family with sequence similarity 83 member A) plays a vital role in tumorigenesis and malignant progression in some human cancer types. The present study explored the potential mechanism of FAM83A in improving the prognosis of pancreatic cancer patients. Transcriptomic and clinical data from patients were obtained from The Cancer Genome Atlas while FAM83A expression was measured in tumorous pancreatic tissue compared with normal controls by quantitative real-time PCR and immunohistochemistry. FAM83A is a vital prognostic indicator and potential oncogene in pancreatic cancer via pan-cancer analysis. In silico analysis revealed that AL049555.1/hsa-miR-129-5p axis was the pivotal upstream ncRNA- mediated pathway of FAM83A in pancreatic cancer. Furthermore, FAM83A expression was related to immune cell infiltration through vital immune-related genes including programmed cell death 1 (PDCD1), and tumorigenesis through common mutation genes including KRAS protooncogene GTPase (KRAS), and SMAD family member 4 (SMAD4). In summary, ncRNA-mediated upregulation of FAM83A is associated with poor long-term survival and immune cell infiltration in pancreatic cancer. FAM83A may be used as a novel survival-related and immune-related biomarker. This information suggests that FAM83A may be a novel therapeutic target for combined or individual treatment for patients with pancreatic cancer.

Hospital Designations and Their Impact on Guideline-Concordant Care and Survival in Pancreatic Cancer. Do They Matter?

Pancreatic ductal adenocarcinoma (PDAC) requires complex multidisciplinary care. European evidence suggests potential benefit from regionalization, however, data characterizing the ideal setting in the United States are sparse. Our study compares the significance of four hospital designations on guideline-concordant care (GCC) and overall survival (OS). The Texas Cancer Registry was queried for 17,071 patients with PDAC treated between 2004 and 2015. Clinical data were correlated with hospital designations: NCI designated (NCI), high volume (HV), safety net (SNH), and American College of Surgeons Commission on Cancer accredited (ACS). Univariable (UVA) and multivariable (MVA) logistic regression were used to assess associations with GCC [on the basis of National Comprehensive Cancer Network (NCCN) recommendations]. Cox regression analysis assessed survival. Only 43% of patients received GCC. NCI had the largest associated risk reduction (HR 0.61, CI 0.58-0.65), followed by HV (HR 0.87, CI 0.83-0.90) and ACS (HR 0.91, CI 0.87-0.95). GCC was associated with a survival benefit in the full (HR 0.75, CI 0.69-0.81) and resected cohort (HR 0.74, CI 0.68-0.80). NCI (OR 1.52, CI 1.37-1.70), HV (OR 1.14, CI 1.05-1.23), and SNH (OR 0.78, CI 0.68-0.91) all correlated with receipt of GCC. For resected patients, ACS (OR 0.63, CI 0.50-0.79) and SNH (OR 0.50, CI 0.33-0.75) correlate with GCC. A total of 43% of patients received GCC. Treatment at NCI and HV correlated with improved GCC and survival. Including GCC as a metric in accreditation standards could impact survival for patients with PDAC.