bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I study of olaparib in combination with capecitabine-based chemoradiation (CRT) in patients (pts) with locally advanced pancreatic cancer (LAPC).
Authors: Evans T.R. Jeffry , Eatock Martin McKinlay , Lewsley Liz-Anne , Kelly Caroline , McCartney Elaine , Duffton Aileen , Houston Peter , Harrison Claire , Purcell Colin , Ashton Miranda , Morton Alanna , Graham Jill , Chalmers Anthony J. , Thomson Fiona , Pou Chantevy , Bilsland Alan , Cooke Susie , McIntosh David , Grose Derek B. 
Published: February 2020

709 Background: Olaparib is a potent inhibitor of PARP-1, which has a critical role in signalling DNA single strand breaks (SSB) as part of the base excision repair pathway, and may have radio-sensitizing effects due to impaired resolution of radiation induced SSB. We hypothesize that O may potentiate the effects of X-CRT in pts with LAPC. Methods: Eligible pts with LAPC, ECOG < 1, tumor diameter < 6cm, with stable disease (SD) or response after 12 weeks’ induction chemotherapy, were treated with 1 of 4 escalating doses of O given bid po starting on day -3, and then in combination with X (830 mg/m2 bid) and radiation (50·4 Gy in 28 fractions) all administered Mon-Fri. Dose limiting toxicities (DLT) were determined on clinical and lab toxicity assessments (NCI-CTC AE v4.03) performed weekly from the start of O until completion of O plus X-CRT (i.e. 6 weeks). Dose escalation continued with a rolling-six design until the Maximum Tolerated Dose (MTD) was reached. Blood samples for PK analyses of O and PD measurement (inhibition of PARP activity) were collected on day -3 (O monotherapy) and during week 1 of O + X-CRT. Results: 18 pts, (9 m, 9 f, ECOG 0/1 [n=6/12]), age range 49-81 (median=70) years, with histologic (14) or cytologic (4) proven LAPC, had received induction chemotherapy with gemcitabine [GEM] (n=2), GEM + X (12), or FOLFIRINOX (3) with partial response (n=4) or stable disease (14). Pts received 50 (3), 100 (4), 150 (6), or 200 (5) mgs bid of O with X+CRT. DLTs were observed in 2 pts (both at 200mgs bid): 1 pt with grade 3 nausea (on optimal anti-emetics) and grade 3 fatigue, 1 pt with grade 3 anorexia. 6 pts were subsequently recruited at 150mgs bid with no DLTs. No pts had complete response, 2 pts had partial response (1 pt each at 100 and 150 mgs bid) and 1 pt (at 100 mgs bid) had progressive disease; the remaining 14 pts had SD. Conclusions: The recommended dose (RP2) of O is 150mgs bid when given in combination with X + CRT in LAPC. Recruitment of up to 12 pts with borderline operable LAPC at the RP2 is ongoing. PK analyses of O, PD studies (PARP inhibition – PBMCs; cytokeratin 18 – serum; γH2AX foci – hair follicles), and exploratory predictive marker studies (tumor – NGS; RNA exome sequencing) are ongoing. Clinical trial information: ISRCTN10361292.
Phase Ia, first-in-human study of AbGn-107, a novel antibody-drug conjugate (ADC), in patients with gastric, colorectal, pancreatic, or biliary cancers.
Authors: Ko Andrew H. , Coveler Andrew L. , Schlechter Benjamin L. , Bekaii-Saab Tanios S. , Wolpin Brian M. , Clark Jeffrey William , Cheng Yi-Lin , Cheng Ting-Ying , Langecker Peter J. , Lin Shih-Yao 
Published: February 2020

713 Background: AbGn-107 is an ADC directed against AG-7 antigen, a Lewis A-like glycol-epitope expressed in 24-61% of gastric (G), colorectal (CRC), pancreatic (PDA), and biliary (BIL) cancers. Based on promising antitumor activity of AbGn-107 in both in vitro and in vivo preclinical studies, we performed a Phase Ia trial in pts with the aforementioned GI malignancies. Methods: Standard 3+3 dose escalation was used. Key eligibility criteria: locally adv or metastatic G, CRC, PDA, or BIL cancer, previously treated, ECOG PS 0-1; positive AG-7 expression was not required. Two dosing intervals were tested: AbGn-107 administered i.v. Q4 weeks (at doses ranging from 0.1-1.2 mg/kg) and Q2 weeks (at doses from 0.8-1.0 mg/kg). DLTs were based on grade 3/4 hematologic and non-heme AEs occurring during the initial 4-week rx window. Pts were treated until dz progression or unacceptable toxicity, with tumor assessments Q8 weeks. 1o objectives: safety and MTD; 2o objectives: PK, immunogenicity, and efficacy defined by ORR (RECIST 1.1). Results: 35 patients were enrolled across 6 dose levels (median age 61.5 yo (range 40 – 81); G (0)/CRC (12)/PDA (20)/BIL (3); median # lines of prior rx = 3 (range 1-7). Safety: 5 pts experienced Grade 3 or 4 neutropenia, all at higher dose levels, with 1 episode of febrile neutropenia. Other frequent drug-related AEs, mostly grade 1/2, inc. fatigue (29%), nausea (20%), and diarrhea (14%). DLTs include grade 4 CK elevation (n = 1) at 0.8 mg/kg Q4W and grade 3 arthralgias (n = 1) at 1.2 mg/kg Q4W. MTD was not reached at either 1.2 mg/kg Q4W or 0.8 mg/kg Q2W; the 1.0 mg/kg Q2W cohort will complete enrollment in Oct 2019. Efficacy: Median duration of treatment = 56 days (range, 8 – 225 days); best response observed to date is stable dz lasting > 6 months at 0.8 mg/kg Q4W and Q2W cohorts (n = 1 each). Conclusions: Overall, AbGn-107 appears well-tolerated with encouraging prelim signs of efficacy (prolonged dz control) in non-biomarker selected pts with advanced GI cancers. Pre-screening for high AG-7 expression is underway for subjects with G, CRC, PDA, and BIL cancers for the cohort expansion phase of this study, which will be open across multiple sites in U.S. and Taiwan. Clinical trial information: NCT02908451.
Homologous recombination deficiency (HRD) by BROCA-HR and survival outcomes after surgery for patients (pts) with pancreatic adenocarcinoma (PC): A single institution experience.
Authors: Chang Amy E. , Zhen David Bing , Radke Marc , Baker Kelsey K. , Coveler Andrew L. , Wong Kit Man , Pillarisetty Venu Gopal , Redman Mary Weber , Swisher Elizabeth , Chiorean E. Gabriela 
Published: February 2020

732 Background: 5-7% of PC pts exhibit deleterious germline mutations (MUT) in HR tumor suppressor genes BRCA1 and BRCA2. BROCA-HR is a targeted capture and massively parallel sequencing assay designed to detect all mutation classes including gene rearrangements, copy number variations, and gene aberrations within the Fanconi Anemia-BRCA HR, non-homologous end joining (NHEJ) DNA repair, and DNA mismatch repair pathways. BROCA-HR has been successfully used in breast and ovarian cancer pts for overall prognosis and prediction of response to platinum-based therapies. While BRCA1/2 MUT may confer survival advantage for PC pts if treated with platinum-chemotherapy, the survival impact of HRD is less well defined. Methods: We retrospectively identified 100 consecutive pts who underwent surgical resection for suspected PC at University of Washington Medical Center between 1999 and 2008. Formalin-fixed paraffin embedded resected tumors were sequenced using BROCA-HR. HRD was grouped based on the following deleterious genetic mutations: 1) BRCA1, BRCA2; 2) core HRD: BARD1, BRIP1, RAD51C, RAD51D, PALB2, CDK12, NBN; 3) non-core HRD: ATM, ATR, ATRX, BAP1, BLM, CHEK1/2, ERCC, FANC A/C/D2/E /F/G/L, MRE11, RAD50/51/51B, RIF1, SLX4; 4) HR proficient. Overall survival (OS) was measured from diagnosis until death or last follow-up. Results: 95 pts had histologically confirmed PC, and 81 pts had adequate tumor DNA for analysis. Six pts (7%) had BRCA1/2 MUT (n = 5), or BRCA1 methylation (n = 1), 1 pt (1%) had non-BRCA core HRD ( PALB2 MUT), 7 pts (9%) had non-core HRD: ERCC (2), CHEK2 (2), ATR, RAD51D, and FANCA MUT (1 each). Median OS was: all pts 1.93 yrs (95% C.I. 1.53, 2.16), BRCA1/2 pts 3.09 yrs (95% CI 0.41, 12.21), all core HRD pts 1.21 yrs (95% CI 0.41, 12.21), all core and non-core HRD pts 1.89 yrs (95% CI 0.57, 4.96), HR proficient pts 1.93 yrs (95% CI 1.51, 2.15). There were no OS differences between pts with HRD vs those HR proficient. Conclusions: HRD is common (17%) but does not affect OS for pts with resected PC. Prospective clinical trials should test neo/adjuvant therapies including platinum chemotherapy and PARP inhibitors for pts with HRD.
Tumor infiltration and cytokine biomarkers of prostate stem cell antigen (PSCA)-directed GOCAR-T cells in patients with advanced pancreatic tumors.
Authors: Shaw Joanne , Ballard Brandon , Yi Xiaohui , Malankar Aditya , Collinson-Pautz Matthew R. , Becerra Carlos Roberto , Woodard Joseph Paul , Foster Aaron E. 
Published: February 2020

734 Background: PSCA is a cell surface protein overexpressed in approximately 60% of pancreatic cancers. BPX-601 is an autologous GOCAR-T cell therapy engineered to express a PSCA-CD3ζ CAR and the MyD88/CD40 (iMC) costimulatory domain activated by rimiducid (Rim), designed to boost CAR-T performance in solid tumors. The safety and activity of BPX-601 activated with Rim in PSCA+ metastatic pancreatic cancer is being assessed in a Phase 1/2 clinical trial, BP-012 (NCT02744287). Methods: Phase 1 of BP-012 is a 3+3 dose escalation of BPX-601 (1.25-5 x106/kg) administered on Day 0 with a single, fixed-dose of Rim (0.4 mg/kg) on Day 7 in subjects with previously treated PSCA+ metastatic pancreatic cancer. All 5 subjects in cohort 5B received Flu/Cy lymphodepletion followed by BPX-601 (5 x106/kg) and Rim. BPX-601 kinetics, PBMC phenotype, and serum cytokines were assayed by qPCR, flow cytometry, and cytokine multiplex, respectively. Baseline and on-treatment biopsies were evaluated by RNAscope in situ hybridization. Results: BPX-601 cells expanded in all subjects and persisted up to 9 months (median 42 days). Transient reduction in BPX-601 vector copy number and total T cell count concurrent with Rim infusion, supports margination of activated BPX-601 cells. Increased serum cytokines, such as IFN-γ and GM-CSF, were observed following BPX-601 infusion with further elevation after Rim activation. All subjects with evaluable on-treatment biopsies had infiltration of BPX-601 cells (n = 3) proximal to tumor cells 7-15 days after Rim, but not in an end of treatment biopsy > 200 days after Rim (n = 1). Stratification by best response (RECIST 1.1) revealed stable disease in 3 subjects and progressive disease in 2 subjects was potentially associated with distinct cytokine signatures. Conclusions: BPX-601 GOCAR-T cells expand and persist in patients with PSCA+ metastatic pancreatic cancer and infiltrate metastatic lesions. A peripheral cytokine signature was observed following BPX-601 infusion. Select cytokines were enhanced after GOCAR-T cell activation and may correlate with clinical response. A cohort of subjects exploring serial administration of Rim is open for enrollment. Clinical trial information: NCT02744287.
Comparison of gemcitabine delivery and tumor response in a pressurized pancreatic retrograde venous infusion versus systemic infusion in an orthotopic murine model.
Authors: Vicente Diego , Shankara Narayanan Jayanth , Ray Partha , Chai Louis F. , Erdem Suna , Carr Matthew , Capacio Benedict , Cox Bryan , Jaroch David , Katz Steven C. , White Rebekah Ruth 
Published: February 2020

737 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with limited response to systemic therapy (ST). Elevated tumor interstitial fluid pressures (IFP) inhibit penetration of ST. Regional Pressure Enabled Drug Delivery has recently demonstrated improved response for liver tumors in a clinical trial. However, this delivery method has not been evaluated in PDAC. We compared gemcitabine (Gem) by systemic delivery vs. a novel pressurized Pancreatic Retrograde Venous Infusion (PRVI) method in an orthotopic PDAC mouse model. Methods: PDAC murine cell line (KPC4580P) tumors were transplanted onto the pancreatic tail of C57BL/6J mice. Groups of 15 mice were randomly assigned to PRVI Gem, PRVI saline (Control), or intraperitoneal Gem (Systemic) groups. Five mice from the PRVI and Systemic groups were randomly selected after one hour post infusion to evaluate Gem tumor concentrations by liquid chromatography - tandem mass spectrometry (ng/mg), and the remainder of mice were euthanized after 7 days to evaluate treatment response. Results: Tumor concentrations of Gem were significantly higher following PRVI compared to Systemic (128 vs. 19, p < 0.01) at one hour after treatment. Seven days after treatment, PRVI Gem mice demonstrated lower mean tumor volume (mm3) than Systemic Gem and Control mice (274 vs. 857 vs. 629, p < 0.01), respectively. Histologic evaluation of tumors demonstrated decreased cellularity in the PRVI Gem mice compared to Systemic and Control mice (35 vs. 78 vs. 71%, p = 0.01), respectively. No differences were seen in Ki67% or immune cell infiltrate between groups. Conclusions: PRVI delivery resulted in increased PDAC Gem concentrations and improved treatment responses with decreased tumor burden and cellularity. These findings suggest that pressurized regional chemotherapy infusion overcomes the elevated PDAC IFP and justifies additional translational pre-clinical studies with other chemotherapeutics (including immunomodulating antibodies) with different physicochemical properties.
Pharmacogenomic blood-based assay to predict chemotherapy response and survival in pancreatic cancer.
Authors: Yu Kenneth H. , McCarthy Brian , Isacoff William H. , Cooper Brandon , Bartlett Andrew , Park Jennifer , Purcell Fay , McCarthy Devan , O'Reilly Eileen Mary 
Published: February 2020

738 Background: Pancreatic adenocarcinoma (PDAC) is for most patients a refractory disease. Modern cytotoxic chemotherapeutics (C) are not yet optimal for inducing responses and extending life. We are developing a blood-based pharmacogenomic (PGx) assay profiling circulating tumor and invasive cells (CTICs) to predict sensitivity and resistance to C. Methods: The PGx assay was studied in two cohorts of patients (pts) presenting for frontline C therapy of metastatic PDAC. Cohort 1 is from an ongoing prospective study (planned n=80); pts are enrolled prior to receiving either FOLFIRINOX or gemcitabine (Gem)/nab-paclitaxel (Nab-P). Cohort 2 (n=50) consists of pts enrolled prior to receiving bespoke combinations of C agents informed by the assay. 6 mL of peripheral blood was collected from pts at baseline and while on C therapy. CTICs were isolated by previously described collagen invasion assay, total RNA was extracted and gene-expression analysis was performed. PGx models for seven C agents used in PDAC were applied, and correlated to treatment received. Pts were classified as sensitive if C received were predicted to be effective and resistant if not. Objective endpoints were PFS and OS. Results: Cohort 1 patients who received sensitive first-line C combinations experienced significantly longer time to progression (TTP) v resistant (Table). In Cohort 2, the PGx assay was predictive of TTP and OS when used across multiple lines of therapy, with a two-year survival of 38%. Greater OS was observed in Cohort 2 pts receiving heterogenous C regimens more highly correlated to those predicted by the PGx assay. Conclusions: The PGx assay has promising predictive performance in both standard and personalized C regimens. A prospective, directed trial comparing these approaches is warranted. Clinical trial information: NCT03033927. [Table: see text]
Prognostic utility of inflammation biomarkers in a PDAC trial involving the human anti-CTGF antibody pamrevlumab.
Authors: Sternlicht Mark D. , Li Dongxia , Nguyen Viet-Tam , Carney Mairead , Zhou Duo , Lipson Kenneth E. , Kouchakji Elias , Picozzi Vincent J. , Carrier Ewa , Seeley Todd W. 
Published: February 2020

752 Background: Pancreatic ductal adenocarcinomas (PDAC) often exhibit desmoplasia, elevated CTGF (connective tissue growth factor) expression and inflammation. The influence of inflammation on patient outcomes was examined in a dose-ranging trial of the anti-CTGF antibody pamrevlumab in combination with a fixed regimen of gemcitabine and erlotinib in locally advanced or metastatic PDAC patients (NCT01181245; Picozzi et al. J Cancer Clin Trials 2017 2:123; n = 75). Methods: The prognostic utility of pre-treatment plasma levels of C-reactive protein (CRP), transforming growth factor β1 (TGFβ1), albumin, CTGF and CA 19-9 were assessed by univariate and multivariate Cox analysis. Demographic parameters, treatment cohort, and pamrevlumab exposure determined on treatment day 15 were also evaluated, as were changes in biomarker levels over the first four weeks of treatment. Results: Elevated baseline CTGF and CRP were prognostic for shorter overall survival (OS) by univariate analysis (HR = 3.2 for CRP > 10 mg/L, p= 0.00002 and HR = 1.6 for CTGF > 10 ng/mL, p= 0.045). In a five-factor multivariate Cox model that included CRP and TGFβ1 as continuous Ln-transformed variables, performance status, age, and pamrevlumab treatment cohort, cohort assignments associated with increasing pamrevlumab exposure predicted improved OS (HR = 0.87, p= 0.03). Removing CRP from this model reduced the prognostic utility of pamrevlumab cohort assignment and exposure, indicating an important contribution of inflammation to interpretation of treatment outcome. Changes in inflammation biomarkers over the course of treatment were also evaluated, but were not prognostic in this study. Conclusions: In multivariate Cox models, assessment of pre-treatment CRP levels improved ability to detect significant differences in PDAC patient survival outcomes associated with pamrevlumab treatment. Our results emphasize the utility of accounting for pre-treatment CRP levels as an independent prognostic factor in PDAC treatment effect models.
Serum glycoproteomic-based liquid biopsy for the detection of pancreatic ductal adenocarcinoma.
Authors: Kasi Pashtoon Murtaza , Shen Ling , Ramachandran Prasanna , Moser Kaitlynn , Xu Gege , Buckley Padraig , Serie Daniel , Lebrilla Carlito , Xu Hui , Chan Carlos Hou Fai 
Published: February 2020

763 Background: Non-invasive biomarkers with high sensitivity and specificity would be of great value for patients with Pancreatic Ductal Adenocarcinoma (PDAC). This would aid in early detection and serve other purposes that 'liquid biopsies' are being explored in. Besides circulating tumor DNA (ctDNA) and methylation markers, glycosylation markers hold great potential promise. We developed a novel workflow using high-resolution quantification of site-specific protein glycosylation by liquid chromatography and tandem mass spectrometry to evaluate the clinical utility of glycoprotemics signature for patients with PDAC. Methods: Serum samples from newly diagnosed PDAC patients and controls were obtained from a commercial biobank (Indivumed, Hamburg, Germany), and a panel of 504 glycan motifs, representing 73 previously reported proteomic markers, was determined. Age-adjusted generalized linear regression models were used to evaluate the differential abundance of each marker, and stepwise variable selection was used for model construction. Results: We analyzed 45 PDAC and 136 control samples. PDAC patients (60% male) had a mean age of 67 (±11) years. with 4.4%, 71.1%, 4.4%, and 20% at stage 1, 2, 3,4, respectively. Controls were women with benign histology after pelvic mass surgery; with a mean age of 61 (±11) years. Twenty-six glycoproteomic markers showed statistically highly significant differential abundance among cases and controls (p<1e-4 each) and were highly reproducible(Pearson’s r > 0.85), which were glycoforms in proteins that have previously been found to be associated with PDAC. Fourteen of these markers displayed >0.8 area under the curve of the receiver operating characteristic (AUC). Multivariate logistic regression modeling with backward selection yielded a classification model with an AUC of 0.94 (95% CI: 0.89-0.99), sensitivity of 91% (95% CI: 75-97%) and specificity of 86% (95% CI: 81-92%). Conclusions: Circulating glycoproteomic biomarkers may be useful in the early detection and clinical management of PDAC patients; offering a new platform to explore and validate.
Survival outcomes of pancreatic intraepithelial neoplasm (PanIN) versus intraductal papillary mucinous neoplasm (IPMN) associated pancreatic adenocarcinoma.
Authors: McGinnis Timothy , Bantis Leonidas , Madan Rashna , Dandawate Prasad , Kumer Sean , Schmitt Timothy , Paluri Ravi Kumar , Saeed Anwaar , Kasi Anup 
Published: February 2020

766 Background: Pancreatic intraepithelial neoplasms (PanINs) and intraductal papillary mucinous neoplasms (IPMNs) are common pancreatic adenocarcinoma precursor lesions. However, data regarding their respective associations with prognosis is lacking. Methods: We retrospectively evaluated 72 resected pancreatic adenocarcinoma cases at the KU Cancer Center between Aug 2009 and March 2019. Patients were divided into either one of two groups, PanIN or IPMN, based on the results of the surgical path report. We compared baseline characteristics, overall and progression free survival between the two groups, as well as OS and PFS based on local or distant tumor recurrence. Results: 52 patients had PanIN and 20 patients had IPMN. Demographic and baseline characteristics are as follows (PanIN/IPMN): Median age 62.5/69; Gender (male) 63%/65%; ECOG status (0-1) 98%/85%; pancreatic head tumors 87%/70%; pancreatic body tumors 6%/15%; pancreatic tail tumors 7%/15%; Abnormal CA19-9 at diagnosis 79%/67%; Comorbidity Index 5/5 respectively. Median PFS was 26.2 months (95% CI: 21.4-31.0) for PanIN and 74.3 months (95% CI: 15.7-132.9) for IPMN [p = 0.004]. Median OS was 70.3 months (95% CI: 35.4-105.2) for PanIN and 78.8 months (95% CI: 33.2-124.4) for IPMN [p = 0.013]. Within the PanIN group, median OS after recurrence was 71.3 months (95% CI: 68.8.-73.4) for local recurrence and 46.7 months (95% CI: 39.2-54.2) for distant recurrence [p = 0.330]. Conclusions: Patients who had a IPMN associated pancreatic cancer had better PFS and OS when compared to patients with PanIN associated pancreatic cancer. In patients with PanIN associated cancer that recurred, OS was better with local recurrence compared to distant recurrence but did not meet statistical significance. The results need to be validated in a larger cohort. [Table: see text]
Young-onset pancreas cancer (PC) in patients less than or equal to 50 years old at Memorial Sloan Kettering (MSK): Descriptors, genomics, and outcomes.
Authors: Varghese Anna M. , Singh Isha , Singh Ritu Raj , Capanu Marinela , Chou Joanne F. , Wong Winston , Stadler Zsofia Kinga , Salo-Mullen Erin E. , Iacobuzio-Donahue Christine A , Kelsen David Paul , Park Wungki , Yu Kenneth H. , O'Reilly Eileen Mary 
Published: February 2020

774 Background: For individuals ≤ 50 years old, cancer incidence is increasing, particularly gastrointestinal and obesity related cancers (Sung, Lancet Public Health 2019). Limited details are known about young onset PC. Herein, we report the epidemiologic, pathologic, and molecular characteristics of PC in patients (pts) ≤ 50 years. Methods: MSK institutional database was queried for medical and treatment history, genomics, and outcomes in pts ≤ 50 years old diagnosed with PC between January 2008 and July 2018. Neuroendocrine cancers were excluded. Overall survival (OS) from date of PC diagnosis was estimated using Kaplan-Meier methods. Results: N = 450 pts ≤ 50 years old with a diagnosis of PC were identified. Ninety-six percent had adenocarcinoma, and 4% had acinar cell carcinoma/other histologies. Table summarizes demographics. Median OS was 16 months in the entire cohort and 11.3 months in stage IV disease. For N = 236 pts diagnosed after 2014, 119 (50%) underwent successful somatic testing with at least one alteration identified, and 21/119 tumors were RAS wild-type with identification of several actionable alterations (NRG1 fusions (n=2), NTRK fusions (n=2), IDH1 R132C (n=1), and microsatellite unstable tumors (n=1) ). N = 114 pts had germline testing (routine after 2015), and 33/114 (29%) had pathologic germline alterations, including BRCA1/2 (n=18), CHEK2 (n=3), PALB2 (n=3), ATM (n=2), MLH1 (n=1), and MSH3 (n=1). Conclusions: Pathogenic germline alterations are present in a substantial percentage of pts with young onset PC, and actionable somatic alterations were seen frequently in the subgroup of young onset PC RAS-wild type tumors. These observations underpin the need for germline and somatic profiling in PC. [Table: see text]