bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world timelines of BRCA1/2-related molecular testing in pancreatic cancer.
Authors: Li Weiyan , Amin Suvina , Joo Seongjung , Adeboyeje Gboyega , DeArbeloa Patricia , Petricoin Emanuel , Blais Edik Matthew , Pishvaian Michael J. 
Published: January 2022

601 Background: BRCA1/2 mutations are present in ̃6-8% of patients with pancreatic adenocarcinoma. Olaparib is a recently approved PARP inhibitor (PARPi) in the US and Europe for germline BRCA1/2-mutated metastatic PaC in the 1st line maintenance setting following response to at least 16 weeks of a platinum-containing regimen. However, the availability of BRCA1/2 testing results at the time of 1st line and subsequent treatment decisions in the advanced stage has not been established in real-world settings. Methods: Longitudinal clinical/molecular data collected between 1/2012-12/2020 were retrospectively analyzed in 75 PaC pts with germline or somatic BRCA1/2 mutations (BRCA1/2m) who enrolled in Perthera’s US real-world observational registry. Tumor NGS testing results were generated by commercial labs for all patients. Germline status was assessed by a molecular tumor board when testing results are available. BRCA1/2m discovery timing (days since advanced presentation), molecular testing turnaround time (days from physician order to result), and platinum utilization were abstracted from physician records. Associations between BRCA1/2m discovery timing and platinum utilization were evaluated using Fisher’s exact test. Results: At the time of advanced PaC diagnosis, BRCA1/2m status was known in a minority of patients (29% (22 of 75). In the remaining 71% (53 of 75) patients, the median time to report BRCA1/2m status was 76 days (IQR=56-558) following advanced diagnosis. The median tumor NGS testing turnaround time was 35 days after physician order (IQR=24-54). Platinum use in any setting was documented in 85% (64 of 75) of patients and the majority of these patients (62%, 40 of 64) initiated a platinum-based regimen before BRCA1/2m status was first reported. Platinum agents were initiated before 2nd line in 75% (48 of 64) patients, and this was associated with BRCA1/2m identification before advanced diagnosis (p=0.03). Conclusions: BRCA1/2 testing results may not always be available when 1st line regimens are chosen which can impact ideal treatment sequencing in PaC patients. These real-world analyses underscore the importance of upfront BRCA1/2 testing in PaC patients.
The impact of germline and somatic mutations in the homologous recombination repair pathway in pancreatic cancer patients who undergo perioperative chemotherapy.
Authors: Jonsdottir Gudbjorg , Masson Asgeir Thor , Jacobus Laura S. , Churchman Michelle L. , Edge Stephen B. , Noonan Anne M. , Cavnar Michael J. , Ulahannan Susanna Varkey , Sahin Ibrahim Halil Halil , Chan Carlos Hou Fai 
Published: January 2022

602 Background: Limited data is available regarding the effects of germline and somatic mutations in the homologous recombination repair (HRR) pathway in patients with resectable pancreatic cancer and exactly which mutations can be targeted with platinum-based chemotherapy. We aimed to assess the impact of HRR pathway mutations in a large cohort of pancreatic patients who underwent curative intent surgical resection. Methods: Patients with resectable pancreatic cancer who underwent perioperative chemotherapy, diagnosed from 1999-2020 from the participating members of the Oncology Research Information Exchange Network (ORIEN) were included in the study. Patients with germline and somatic whole exome sequencing data were analyzed for known pathogenic and likely pathogenic variants according to ClinVar in the following HRR pathway genes: BRCA1, BRCA2, PALB2, BRIP1, BRAD1, ATM, RAD51C, RAD51, RAD50, CHECK2, FANCC, FANCA, MRE11 and XRCC2. The Kaplan Meier method was used to compare median overall survival (OS) between patients with adenocarcinoma, with and without HRR pathway mutations. Multivariate cox proportional hazard model was used to calculate HR and 95% CI adjusting for age at diagnosis, sex and pathologic stage. Results: During the study period, the ORIEN cohort included 417 patients with resectable pancreatic cancer and whole exome sequencing. Of these 313 (75%) patients had adenocarcinoma and 104 (25%) neuroendocrine tumor. A total of 19 patients (5%) had an HRR pathway mutation - 15 (5%) in the adenocarcinoma group and 4 (4%) in the neuroendocrine group. In the adenocarcinoma group, 97 (31%) patients underwent platinum-based perioperative chemotherapy. Median OS was 2.8 years (IQR 2.5-3.3) in the adenocarcinoma group without HRR pathway mutation and 3.8 years (IQR 3.4-NA) in the group with HRR pathway mutation (HR 0.6: 95% CI 0.3-1.4, p = 0.76). Conclusions: There was a trend towards improved survival in patients with adenocarcinoma receiving perioperative platinum-based chemotherapy with HRR pathway mutations compared to those without a mutation. This finding supports previous data in the literature regarding the prognostic role of HRR pathway alterations in pancreatic cancer. Larger prospective studies are needed to assess the predictive role of these mutations in the perioperative setting in response to platinum-based chemotherapy.
The impact of CA 19-9 on survival in patients with clinical stage I pancreatic cancer.
Authors: Melucci Alexa D. , Chacon Alexander C , Burchard Paul R. , Ullman Nicholas A. , Tsagkalidis Vasleios , Casabianca Anthony S. , Reitz Alexandra , Swift David A. , Goyal Subir , Switchenko Jeffrey M. , Carpizo Darren R. , Shah Mihir Maheshkumar 
Published: January 2022

606 Background: Standard of care for early-stage resectable pancreatic cancer (PC) includes a combination of surgical resection and chemotherapy. Frequently, CA 19-9 is used as a biomarker to monitor treatment effect and has prognostic significance. We evaluated the impact of CA 19-9 on overall survival (OS) in patients with clinical stage I PC (cT1N0 and cT2N0) utilizing the National Cancer Database (NCDB). Methods: The NCDB was queried between 2010 and 2014 to identify patients with clinical stage I PC. Patients who had missing or undocumented CA 19-9 value at diagnosis were excluded. Demographic and clinical characteristics were analyzed. Patients were stratified into two cohorts based on the CA 19-9 value at diagnosis – CA 19-9 < 98 U/mL and CA 19-9 > 98 U/mL. Univariable and multivariable analyses were performed, and variables associated with OS were identified. Kaplan-Meier survival curves were computed to compare the OS between the two cohorts. Results: A total of 12,480 patients met our inclusion criteria. A majority of patients were female (51.9%), white (84.4%), with a median age of 70 years. Nearly, half the patients received care in an academic/research program (49.5%). A majority of patients had tumors located in the head of the pancreas (71.9%), and received single-agent (35.1%) or multiagent (22.9%) chemotherapy. Over half the patients (6505 patients, 52.1%) had a CA 19-9 value > 98 U/mL. A CA 19-9 value > 98 U/mL in patients predicted a significantly shorter median OS of 12.1 months compared to 19.4 months in patients with a CA 19-9 < 98 U/mL, p<0.0001 (Table). The 5-year OS rate was 9.9% in patients with a CA 19-9 value of > 98 U/mL compared to a 5-year OS rate of 18.1% for patients with a CA 19-9 value < 98 U/mL. On multivariable analysis, CA 19-9 > 98 compared to CA 19-9 < 98 (HR 1.53, p<0.001) and black race compared to white race (HR 1.10, p<0.001) was associated with worse survival, whereas tumor location in the body and tail compared to the head (HR 0.82, p<0.001), single-agent (HR 0.55, p<0.001) and multiagent (HR 0.55, p<0.001) chemotherapy compared to no chemotherapy, independently predicted improved OS. Conclusions: This is the first National Cancer Database study to demonstrate the prognostic value of CA 19-9 in patients with clinical stage I pancreatic cancer, with a value < 98 U/mL predicting improved survival. Clinical stage I pancreatic cancer patients appear to derive a significant benefit from chemotherapy, including single and multiagent chemotherapy, irrespective of the CA 19-9 value.[Table: see text]
High-plex proteomic prognostic marker discovery for patients with pancreatic cancer adenocarcinoma using digital spatial profiling.
Authors: Jamieson Nigel Balfour , Legrini Assya , Leslie Holly , Dreyer Stephan , Biankin Andrew V , Chang David Kuang-Fu 
Published: January 2022

611 Background: The long-term outcomes following surgical resection for Pancreatic Ductal Adenocarcinoma (PDAC) remain poor, with only 20% of patients surviving 5 years after pancreatectomy. With its immune-privileged nature, starting from the early pre-neoplastic state, it appears to escape easily from the antitumor immune response. Despite rationale for targeting immune pathways in PDAC, there has been little benefit observed at this point. The aim of the current study was to interrogate immune landscape of PDAC utilising the Nanostring GeoMx Digital Spatial Profiler (DSP), a state-of-the art analysis platform enabling Hi-plex proteomic characterisation whilst maintaining tumor microenvironment (TME) topographical features. Methods: We assessed Formalin Fixed Paraffin Embedded (FFPE) tumor samples from 28 treatment-naive PDAC cases represented in a multi-regional tissue microarray (TMA) for which extensive IHC, molecular, genomic characterisation and clinicopathological follow-up data is available. Following multiplex IHC staining for DAPI, panCK, aSMA and CD3 to guide region selection, we employed the GeoMx DSP system (NanoString) to select regions within multiple TMA cores. We quantified 60 immune markers simultaneously in multiple tissue compartments defined by immunofluorescence co-localization including (tumor [panCK+ve], immune stroma (PanCK-ve]. Data analysis was performed by a combination of DSP analysis suite and custom R pipeline. Results: The spatially informed variable assessment by DSP was validated by both regression and variable prognostication compared with IHC for stromal CD3, CD8 CD68 in near serial TMA PDAC sections. Unsupervised analysis of DSP proteome data in the panCK-negative regions identified an immune poor group associated with shorter Overall Survival (OS) (13.0 versus 31.1months, P = 0.005). When transcriptomic subtype was considered, the checkpoint inhibitor B7-H3 was significantly upregulated in the squamous subtype tumours versus the classical group (Log2: 1.63, P = 0.001). Patients with high B7-H3 expression, using a median expression cut-off, were associated with shorter OS on multivariate analysis (Hazard Ratio: 4.16, P = 0.01) including lymph node and resection margin status, a finding that was validated in an external cohort at the transcriptome level. Conclusions: This pilot scale discovery study shows the potential of the Nanostring DSP technology in the identification of spatially-informed biomarkers with prognostic relevance in biopsy sized samples from treatment-naive PDAC. We identified a number of relevant candidate immune predictors in spatial context that are currently undergoing validation in larger independent cohorts and the neoadjuvant setting. Future studies will apply this technology to pre- and post-treatment biopsy samples.
Association of pancreatic adenocarcinoma location (head/body/tail) with DDR mutation status and response to platinum-based therapy.
Authors: Micaily Ida , Blais Edik Matthew , Cohen Steven J , Cannaday Shawnna , Krampitz Geoffrey , Wadlow Raymond Couric , Shroff Rachna T. , McRee Autumn Jackson , Chuy Jennifer W. , Zheng Lei , Hendifar Andrew Eugene , Matrisian Lynn McCormick , Gregory Gary Lee , Thach Dzung , Brody Jonathan Robert , Petricoin Emanuel , Pishvaian Michael J. , Lavu Harish , Yeo Charles , Basu Mallick Atrayee 
Published: January 2022

612 Background: Pancreatic adenocarcinoma is an aggressive disease with poor clinical prognosis that can originate from either the head (H) or body/tail (BT). Potential prognostic implications for H versus BT tumors have been reported; however, the molecular underpinnings associated with these differences in survival have not fully been explored. Using a large-scale real-world cohort of H and BT tumors with NGS results available from commercial labs, we retrospectively aim to identify potential differences between H and BT tumors in their response to standard therapies to help understand whether the treatment prioritization for pancreatic adenocarcinoma should take into account anatomical sidedness, as is recognized today with left-sided versus right-sided colorectal cancers. Methods: We analyzed outcomes across 1540 pts with NGS results from Perthera’s Real-World Evidence database who were diagnosed with PDAC originating from the H or BT. Progression-free survival (PFS) was evaluated from initiation of 1st line for advanced disease until discontinuation due to disease progression. Hazard ratios and p-values were computed via Cox regression when comparing PFS between 1st line FOLFIRINOX and gemcitabine/nab-paclitaxel. Differences in frequencies of genomic alterations between proximal and distal were analyzed by Fisher’s exact test. Results: Mutations in BRCA1/ BRCA2/ PALB2 were enriched (unadjusted p-value=0.017) in BT tumors (8.6% of 619) relative to H tumors (5.4% of 921). An expanded set of DDR pathway alterations (e.g. ATM, FANCA, CHEK2, BAP1, BRIP1, etc) were also enriched (unadjusted p-value=0.003) in BT tumors (21.4% of 619) relative to H tumors (15.6% of 921). In BT tumors, mPFS on 1st line FOLFIRINOX was longer (Table) than 1st line gemcitabine/nab-paclitaxel (p=0.0078) but this difference was not observed in H tumors (p=0.34). Overall survival data in these patients and an independent institutional cohort which motivated these analyses will also be discussed. Conclusions: DDR pathway alterations are known predictors of increased benefit from platinums and these real-world insights preliminarily suggest that DDR mutations are more common in BT vs. H. Prospective studies may be warranted to confirm the hypothesis-generating findings that platinum-based regimens should be prioritized in patients with BT tumors while underscoring the importance of routine NGS testing in both BT and H tumors given the prevalence of DDR pathway alterations on both sides of the pancreas.[Table: see text]
Pancreatic cancer: Cutaneous metastases, clinical descriptors and outcomes.
Authors: Gu Lilly , Paras Mehta , Rao Devika , Rotemberg Veronica , Capanu Marinela , Chou Joanne F. , Sigel Carlie S. , Busam Klaus J. , Boyce Lindsay , Gordon Allison , O'Reilly Eileen Mary 
Published: January 2022

615 Background: The occurrence of cutaneous metastasis from pancreatic cancer (PC) is rare, and the exact incidence is unknown. The literature to date is primarily limited to isolated case reports. Herein, we evaluate the clinical, genomic, and other descriptors of patients with PC and cutaneous metastases. Methods: Institutional databases were queried using search terms “pancreas cancer” and “cutaneous mets”. Clinical history, demographics, PC cutaneous metastasis details, and survival outcomes were abstracted. Results were described using descriptive statistics, and overall survival (OS) from the diagnosis of cutaneous metastasis was estimated using Kaplan-Meier methods. Results: Of 140 on initial search, 40 patients met inclusion criteria of PC and cutaneous metastases and were analyzed. The median age (Q1-Q3, IQR) of pancreatic cancer diagnosis was 66.0 (59.3-72.3, 12.9) years. Most common histologic subtype was adenocarcinoma (n= 39, 98%), and one patient had a neuroendocrine malignancy. Most patients had stage IV disease at diagnosis (n=26, 65%). The most common location of the primary tumor was tail of the pancreas (n=17, 43%). Forty-eight percent (n= 19) had cutaneous metastasis at/within one month of cancer diagnosis. Most patients received chemotherapy (n=37, 93%), with 14 patients (35%) patients also receiving local therapy in the form of local excision or radiation. The most common cutaneous metastasis site was the abdomen (n=40, 66%), with umbilical lesions occurring in 58% (n=23) of abdominal lesions. The median interval (Q1-Q3, IQR) between diagnosis of pancreatic cancer and development of cutaneous metastasis was 1.4 (0-14.5, 14.5) months. The median OS (95% CI) from cutaneous metastasis diagnosis was 11 months (7.0, 20). Table details the observed differences between umbilical vs. non-umbilical metastases. Sixteen of 40 (40%) patients underwent somatic testing. The most frequently mutated genes were KRAS (n= 16, 100%), TP53 (n=7, 44%), CDKN2Ap14ARF (n=5, 31%), CDKN2Ap16INK4A (n=5, 31%), and CDKN2B (n=3, 19%). Germline testing was undertaken in 12 (30%) patients, and pathogenic variants were observed in 3: CHEK2 (n=1, 8%), BRCA1 (n=1, 8%), and ATM (n= 1, 8%). Summary of cutaneous metastasis characteristics. Conclusions: Cutaneous metastases from PC are rare and can be present at the time of diagnosis of stage IV disease, occurring most frequently in the umbilicus. Cutaneous metastases can be classified into umbilical and non-umbilical metastases, which may be due to a different biology.[Table: see text]
Retrospective study of survival outcomes in patients with hereditary pathogenic and variants of unknown significance mutations in pancreatic adenocarcinoma.
Authors: Lin Ching Ying , Moshayedi Natalie , Thomassian Shant , Gong Jun , Osipov Arsen , Hendifar Andrew Eugene 
Published: January 2022

616 Background: Since 2019, all patients with pancreatic adenocarcinoma (PDAC) are recommended to undergo germline testing per the National Comprehensive Cancer Network guidelines. Outside of PARP inhibitors in germline BRCA mutated PDAC, the predictive and prognostic implications of these genetic alterations are unclear. Many hereditable mutations are continually discovered, but the majority are considered Variants of Unknown Significance (VUS). The purpose of this retrospective study is to characterize the clinical characteristics of multiple pathogenic and VUS germline mutations in PDAC. Methods: An IRB approved institutional database of PDAC patients (n=442) was queried for patients diagnosed between 2007 and 2021. Only patients who tested positive for hereditary mutations (n=35) or VUS (n=41) were included. Patients with both pathogenic mutation and VUS were considered in the pathogenic mutation group. Results: 76 patients (35 pathogenic, 41 VUS) were included in the analysis. Pathogenic mutations were divided into subcategories including DNA repair (n=21), polyposis (n=2), pancreatitis-associated (n=11), and other (n=2). With a mean follow-up period of 636 days, the overall survival (OS) for pathogenic mutations at 90 days, 180 days, 1 year, and 2 years was 100%, 97.1%, 88.6%, and 74.3% respectively. The cumulative recurrence was 2.9%, 11.4%, 22.9%, and 37.1%. For VUS, the OS was 97.6%, 95.1%, 75.6%, and 56.1% and cumulative recurrence was 0%, 14.6%, 31.7%, and 43.9% in the same time intervals. Conclusions: This data suggests that patients with germline mutations may have favorable outcomes when compared to the general population. Overall germline alterations in our intuitional cohort had a 2-year survival of nearly 75%. Notably, pancreatitis-associated hereditable mutations consisted a sizeable portion of our overall cohort. Although current therapy is most focused on DNA repair mechanisms, these results show that other novel germline genetic alterations may be prognostic and warrant further investigation.[Table: see text]
Clinical characteristics, treatment, and oncological outcomes in patients with ampullary cancer at a reference center in Mexico.
Authors: Torres Valdiviezo Lucero Itzel , Rodríguez Flores Karla Lucero , Rosas Camargo Vanessa Rosas , Noguez-Ramos Alejandro , Meneses Medina Mónica Isabel , Rosas Flota Ximena , Gamboa Dominguez Armando , Huitzil Melendez Fidel David 
Published: January 2022

617 Background: Ampullary cancer (AC) represents 0.2% of gastrointestinal cancers. Given the rarity of the disease, information regarding treatment strategies and outcomes derives from studies that include the different types of periampullary cancers, which constitute a heterogeneous group. Our aim was to describe the clinical characteristics, treatment modalities and outcomes in patients (pts) with true AC treated at our institution. Methods: A retrospective review of medical records of all consecutive pts with histological diagnosis of AC evaluated at our institution from Jan 2009-Dec 2019. Clinical, pathological and laboratory variables at diagnosis were recorded. Overall survival (OS) was estimated by Kaplan-Meier and compared with the Log-rank test. Statistical significance was determined at P<0.05. Results: 133 pts with AC were included. Median age was 62 yo (IQR 53-70), 51.9% were women. 25% had ampullary adenoma history. Symptoms at diagnosis: 89% jaundice, 63% weight loss and 56% abdominal pain. Median laboratory values were total bilirubin 1.7 mg/dL (0.7-5.1), albumin 3.7 g/dL (3.1-4.2), hemoglobin 12.6 g/dL (10.9-14.2), carbohydrate antigen (CA) 19-9 34.7 U/mL (6.4-113.9) and carcinoembryonic antigen (CEA) 2.6 ng/mL (1.2-4.2). Most tumors were moderately differentiated (59%). Histologic subtypes of adenocarcinoma were available in 84 pts: intestinal 46.4%, pancreaticobiliary 39.3% and mixed 14.3%. Stage at diagnosis was localized (46%), locally advanced N+ (29%) and advanced (25%). For those with localized/locally advanced disease, 91% (91/100) underwent surgical resection, 25.3% (23/91) received adjuvant chemotherapy (ChT), 69.6% (16/23) received single agent and 30.4% (7/23) duplet. Pts who received adjuvant Cht presented N+ in 69.6%, moderate differentiation in 73.9%, intestinal 47.8% and pancreaticobiliary subtype 43.5%. In advanced setting, 63.6% (21/33) received palliative Cht, 66.7% received a duplet regimen. Median OS was 32.8 (22.9-42.8) months (mos). Median OS according to stage was 152.1, 28.1 and 10.2 mos for localized, locally advanced, and advanced, respectively (P<0.001). OS univariate analysis is shown in table. Conclusions: Most of pts presented with localized/locally advanced disease, were eligible to surgical resection and had a better survival. For those with N+ disease it is required to evaluate the role of adjuvant Cht. In the advanced setting, Cht improves prognosis.[Table: see text]