bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival analysis of colorectal cancer patients treated with first-line modified FOLFOX6 with or without bolus fluorouracil.
Authors: Shaib Walid Labib , Draper Amber , Kalu Kalu , Byers Kristina F. , El-Rayes Bassel F. , Wu Christina , Alese Olatunji B. , Akce Mehmet , Goyal Subir , Zakka Katerina Mary
Published: January 2021

35

Background: The combination of oxaliplatin, bolus 5-FU (b5FU), infusional 5-FU (5-FUCI), and leucovorin (LV) is the preferred first line treatment option for mCRC. This study evaluates the impact of b5FU on survival in first line therapy for mCRC patients treated with mFOLFOX6. Methods: This was a retrospective chart review of patients ≥ 18 years old with mCRC receiving palliative first line mFOLFOX6 chemotherapy with or without b5FU/ LV from January 1, 2010 through June 1, 2019 at Winship Cancer Institute, Emory University. Data collection included the following: demographics (age, race, gender), disease characteristics (tumor sidedness), microsatellite status, KRAS status, BRAF status, addition of monoclonal antibodies (bevacizumab, panitumumab), ECOG PS, grade 3/4 neutropenic events, addition of growth factors, and treatment delays. The primary endpoint was PFS. The multivariable Cox proportional hazards model for PFS and OS was performed with selected covariates of interest. Results: A total of 252 patients with mCRC met the inclusion criteria. Median follow-up time was 2.4 years. 161 patients (64%) received mFOLFOX6 with b5FU/LV and 91 patients (36%) received mFOLFOX6 with no b5FU/LV. More cycles were delivered in the b5FU group as compared to the non-b5FU group (mean, 4.8 v. 3.8 cycles, respectively; p < 0.001). There were no differences in grade 3 and 4 neutropenic events between groups. Growth factor usage was numerically higher in the bolus group though not significantly different (p = 0.06). No difference was observed in treatment delays between groups (p = 0.83). There was no statistical difference in PFS between treatment groups (1.1 years in the b5FU/LV group v. 0.8 years (95% CI, 0.6-1.0) in the no 5-FU/LV bolus group; p = 0.076). The median OS was 2.5 years in the b5FU/LV group compared to 1.8 years in the no b5FU/LV group (p = 0.012). On univariate analysis, tumor sidedness and performance status were significantly different between groups. On multivariate analysis, none of the variables were significantly different between groups. Conclusions: The omission of the b5FU/LV from mFOLFOX6 does not significantly impact PFS, toxicity or treatment delays. However, OS is significantly shorter when the b5FU/LV is omitted suggesting the clinical importance of maintaining bolus administration with 5-FUCI in the first line palliative treatment of mCRC.
Radiographic response of desmoplastic mesenteric lesions to peptide receptor radionuclide therapy (PRRT).
Authors: Pelle Eleonora , Al-Toubah Taymeyah E. , Morse Brian , El-Haddad Ghassan , Strosberg Jonathan R.
Published: January 2021

362

Background: 177Lu-dotatate PRRT is indicated in well-differentiated, SSTR+ small bowel NETs. These tumors often metastasize to mesenteric lymph nodes and produce a desmoplastic reaction, consisting of tumor cells mixed with fibrotic tissue. We hypothesized that in patients treated with 177Lu-dotatate, mesenteric tumors would remain stable even as liver tumor size changes were observed. Methods: We retrospectively reviewed the records of all patients treated with 177Lu-dotatate between 4/2018 and 12/2019. Among patients with desmoplastic mesenteric tumors and liver metastases, we evaluated changes in tumor size of mesenteric and liver lesions based on pre and post-treatment radiology reports. Due to the infrequency of objective radiographic response (ORR), any reported changes in tumor size were considered significant. Scans were subsequently reviewed by a radiologist to confirm findings. Results: 21 patients met the inclusion criteria: 9 had evidence of shrinkage of liver lesion(s), 1 report described mild progression of liver lesions, 7 described stable hepatic disease and 4 described mixed hepatic progression/response. 2 of the patients with hepatic tumor shrinkage met criteria for PR by RECIST 1.1. Desmoplastic mesenteric lesions remained unchanged in size, regardless of the changes detected on liver lesions. Conclusions: 177Lu-dotatate does not impact desmoplastic mesenteric tumors typically associated with midgut NETs. Patients whose disease is confined to desmoplastic mesenteric lesions are unlikely to respond radiographically to PRRT. Moreover, the inclusion of desmoplastic mesenteric lesions as target lesions in RECIST measurements increases rates of disease stability versus response or progression.
Temozolomide and capecitabine (CAPTEM) is effective in metastatic well-differentiated gastrointestinal neuroendocrine tumors.
Authors: Dogan İzzet , Tastekin Didem , Karabulut Senem , Sakar Burak
Published: January 2021

366

Background: The study aimed to evaluate patients' outcomes and prognosis with metastatic gastrointestinal neuroendocrine tumors (mgNET) who treated temozolomide and capecitabine (CAPTEM). Methods: The data of forty-three patients were retrospectively evaluated. Clinicopathological features and treatment approaches were recorded. Kaplan-Meier analysis was used for overall survival (OS) and progression-free survival (PFS). Prognostic factors were assessed with Cox-regression analysis. Results: Median age was 59 (27-85) years. The number of male and female patients was 23 (%53.5) and 20 (%46.5), respectively. Pancreas (%51.2) was the most common site of the tumor. The number of patients with well- and poorly-differentiated mgNET was 38 (%88.4) and 5 (%11.6), respectively. The most common metastatic sites were liver (%62.8), lymph node (%58.1), and bone (%18.6). Eleven (%25.6) of the patients previously had undergone surgery, and some patients received radiotherapy (%9.5), chemotherapy (%19), and nuclear therapy (%9.3). Also, patients received octreotide (%86) or lanreotide (%14) with CAPTEM. In patients with well-differentiated mgNET, median PFS was 17.4 months, and disease control ratio %79.4 (%3-complete response, %38.2-partial response, and %38.2-stable response). No response observed in patients with poorly differianted mgNET, and the median PFS was calculated as 4.5 months. Grade 1-2 toxicity was observed in 34 (%79.1) of the patients, and grade 3-4 toxicity in 8 (%18.6). Four (%9.5) patients discontinued therapy for the toxicity. The most common toxicities were anemia (%37.2), thrombocytopenia (%25.6), and fatigue (%16.3). At a median follow-up of 33.8 (2.9-172.73) months, the ratio of five-years OS was %61. In multivariate analysis; gender (p=0.008), age (p=0.007), and Ki-67 levels (p=0.011) were a statistically significant for OS. However, the site of the tumor (p=0.186), number of metastatic sites (p=0.255), and type of somatostatin receptor ligand (p=0.903) were not. Conclusions: In the study, we showed that CAPTEM + somatostatin receptor ligands (octreotide or lanreotide) were effective and well-tolerated in patients with well-differentiated mgNET. But, it was not effective in patients with poorly-differentiated mgNET. Male gender, aged over 60 years, and tumor with a high level of Ki-67 were negative prognostic factors.
Incidence and patterns of secondary malignancies in patients with neuroendocrine neoplasms: A SEER database analysis.
Authors: Sadaps Meena , Mehta Neal , Li Hong , Estfan Bassam N.
Published: January 2021

374

Background: Neuroendocrine tumors (NETs) are comprised of a group of biologically and clinically heterogenous malignancies arising from a variety of anatomic sites, the majority of which lie within the gastrointestinal tract. Prior literature has reported on the association between NETs and other primary malignancies (OPM), most of which also end up being within the gastrointestinal tract, but these studies are limited by small sample sizes. We aim to further analyze the association of NETs and OPM on a larger scale using a population-based cancer registry. Methods: Malignant primary cancer with NET features were identified from the Surveillance Epidemiology and Ends Results (SEER) registry between 1975 and 2017. The histology/behavior of NET included carcinoid tumor, neuroendocrine carcinoma, pancreatic endocrine tumor, atypical carcinoid tumor, and other including insulinoma, glucagonoma, gastrinoma, VIPoma, somatostatinoma and enterochromaffin cell carcinoid. First NET observation from each patient was examined. Patients with NET were grouped into three categories: only one primary cancer with NET, first primary cancer with NET and first primary cancer without NET based on sequence number of primary cancer recorded in SEER. Distribution of NET between gastrointestinal (GI) and non-GI sites was described. Demographics were compared by NET sequence group and between GI and non-GI sites. Results: 45,896 patients with NET were analyzed (77.9% Caucasian, 47.0% male, median age 62.0 years). More than half (65.7%) of the NETs were observed in GI sites. Within the GI tract, 31.3% were in the small intestine, 25.1% in the rectum, 16.6% in pancreatobiliary, and < 11% in other GI locations. Age at NET diagnosis was younger in those with GI NETs (median 60.0 vs 65.0, p < 0.001 ). 71.2% of NET found in only cancer diagnosis, 10.4% of NET in first followed by a second primary malignancy, and 18.4% in a non-NET primary followed by NET. Mean age was 58.9 for NET primary only, 61.0 for NET primary first and 68.3 for non-NET primary first (p < 0.0001). More Caucasian patients had non-NET primary first (82.3%) compared to NET primary only (76.9%) and NET primary first (75.5%). No gender differences were observed amongst the three groups. Carcinoid tumor histology was more prevalent in NET primary first (78.6%) compared to NET primary only (67.3%) and non-NET primary first (66.6%), while neuroendocrine carcinoma histology was more prevalent in NET only (27.4%) and non-NET first (29.3%) compared to NET first. Conclusions: 28.8% of patients with NETs were found to have OPM, either preceding or following their NET diagnosis. It is imperative that patients with NET undergo age-appropriate cancer screening to help identify any concurrent malignancies. Further research is warranted to identify the location of such additional malignancies and the timeframe in which they occur in relation to the NET.
Improved overall survival for patients with early-onset pancreatic ductal adenocarcinoma.
Authors: Nair Kanika G. , Kamath Suneel Deepak , Wei Wei , Tullio Katherine , Estfan Bassam N. , Khorana Alok A.
Published: January 2021

379

Background: The median age of diagnosis of pancreatic ductal adenocarcinomas (PDAC) is 70 years. Only about 20% of patients are diagnosed prior to the age of 60. We sought to identify clinical characteristics and outcomes of patients with early-onset PDAC as compared to later-onset PDAC. Methods: We identified histologically confirmed cases of pancreatic adenocarcinoma with information about age and overall survival (OS) diagnosed between 2004 and 2016 from the National Cancer Database (NCDB). Differences in demographic, disease and treatment characteristics and socioeconomic factors between younger and older patients were assessed by Chi-square test. The effect of age, race, insurance status, community median income and community educational attainment on overall survival (OS) were assessed using log rank test. Results: Of 321,896 patients who met inclusion criteria, 71,263 (22%) were younger than 60 years and 250,633 were 60 years of age or older at diagnosis. Median OS for younger patients was 9.5 months, compared to 5.6 months for older patients ( p< 0.0001). Younger patients were more likely to be diagnosed with stage IV disease (47.8% vs 43.4%), to be Black (16.1% vs 10.7%) or Hispanic (6.4% vs 4.5%), have a Charlson-Deyo comorbidity index of 0 (73.5% vs 63.3%), have private insurance (65.1% vs 20.5%), and receive treatment at academic centers (45.9% vs 40.9) (all p< 0.0001). Younger patients were also more likely to receive surgery (26.2% vs 19.5%), radiation (23.0% vs 15.9%), and chemotherapy (65.9% vs 46.7%) (all p< 0.0001). Conclusions: Survival for patients with early-onset PDAC is significantly better than older patients despite more patients being diagnosed with stage IV disease. This may be attributable to younger patients having less comorbidities and receiving more treatment. Concerningly, Black and Hispanic patients make up a larger proportion of younger patients with PDAC, and further work is needed to investigate these differences and underlying causes.
Adjuvant therapy in patients with resected pancreatic adenocarcinoma: Analysis of treatment allocation patterns in a Canadian provincial institution.
Authors: Chahal Manik , Loree Jonathan M. , Lim Howard John , Davies Janine Marie , Renouf Daniel John , Gill Sharlene
Published: January 2021

383

Background: In recent years adjuvant therapy (AT) for pancreatic cancer has evolved. Improved overall survival (OS) was demonstrated first in 2017 with gemcitabine and capecitabine (GemCap), and then further improved in 2018 with FOLFIRINOX compared to gemcitabine (gem) alone. Given these options, we retrospectively reviewed the patterns of AT allocation in the province of British Columbia (BC) during these periods of adoption of newer AT regimens. Methods: Patients (pts) treated at BC Cancer centers between January 2017 to June 2018 (the GemCap era), and July 2018 to July 2019 (the FOLFIRINOX era), who had undergone curative intent resection and received at least one cycle of AT were included for chart review. Patient and disease characteristics, treatment details, and stated rationale for choice of AT regimen were collected. Analyses were performed with one-way ANOVA for comparison of means between regimens, and Chi-squared or Fisher Exact tests to determine correlation between clinicopathologic factors and likelihood of undergoing a given AT regimen. Results: 122 pts were identified: 67 treated in the GemCap era (gem: 25, 37%, and GemCap: 42, 63%) and 55 treated in the FOLFIRINOX era (gem: 18, 33%, GemCap: 18, 33%, FOLFIRINOX: 19, 34%). Examined variables included age, gender, ECOG, T and N stage, margins, lymphovascular invasion and post-operative CA19-9. In the GemCap era, use of GemCap vs Gem was associated with younger average age (p = 0.001) and positive lymph node status (91% vs. 60%, p = 0.005). In the FOLFIRINOX era, use of gem AT was associated with a delayed time from surgery to consultation. (p = 0.036) AT assignment was not influenced by high volume vs low volume centre in the GemCap era; however, pts were more likely to receive GemCap in low-volume centres during the mFOLFIRINOX era (p = 0.045). The most common stated reasons for choice of a less intense AT regimen were pt comorbidities or functional status (GemCap era: 24% and FOLFIRINOX era: 31%). Conclusions: Despite improvements in survival with newer AT regimens, the majority of pts in our real-world setting were assigned a less intense AT regimen. Within the limits of a small sample size, significant pt or disease factors predictive of AT assignment were not identified aside from age and lymph node positivity in the GemCap era, and time from surgery to consultation in the FOLFIRINOX era. Efforts to improve adoption of newer AT regimens and optimize pt eligibility for FOLFIRINOX are warranted.
AGIG chemo-immunotherapy in patients with advanced pancreatic cancer: A single-arm, single-center, phase II study.
Authors: Dai Wangshu , Qiu Xin , Lu Changchang , Zou Zhengyun , Sha Huizi , Kong Weiwei , Liu Baorui , Du Juan
Published: January 2021

384

Background: To date, chemotherapy remains the only effective treatment of unresectable pancreatic adenocarcinoma. In the last few years, the interest in the use of immunological anticancer strategies is greatly increased. AGIG is a novel chemo-immunotherapy regimen that combines nab-paclitaxel + gemcitabine chemotherapy with sequential recombinant interleukin-2 and granulocyte-macrophage colony stimulating factor (GM-CSF) therapy. We conducted a single-arm prospective phase II study to determine the efficacy and safety of the first-line treatment of advanced pancreatic cancer with AGIG regimen. Methods: Nab-paclitaxel (120 mg/m2) and gemcitabine (1000 mg/m2) were administered intravenously to all patients on days 1 and 8 triweekly, interleukin-2 and GM-CSF (100 µg) were administered subcutaneously on days 3-5 after chemotherapy. The primary end point was ORR by the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included safety profile, progression-free survival (PFS), overall survival (OS). Patients’ conditions and the efficacy and safety were assessed every 4 cycles. Results: Between 11/2018 and 01/2020, 64 patients were enrolled. In the 64 evaluable patients, the ORR and DCR were 43.75% and 76.6%, respectively. The median follow-up time was 12.1 (range 7.1–22.4) months, the median PFS was 5.7 (range 1.63–15.8) months, and the median OS was 14.2 (range 2.9–22.0) months. The most common adverse event was fever (75%). The incidence of grade 3/4 neutropenia was 4.69%. In subgroup analyses, we found that eosinophil count in the blood elevated three times higher than baseline level predicted a longer survival. Conclusions: The AGIG Chemo-immunotherapy regimen has presented encouraging ORR, OS, and manageable toxicities as first-line therapy for advanced pancreatic cancer. This regimen may be a novel reliable therapeutic option for patients with preserved performance status. The improvement of treatment efficiency may be related to the activation of non-specific immune response. Clinical trial information: NCT0376867. Research Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School. [Table: see text]
Real-world genomic and treatment landscape in advanced colorectal cancer identifies treatment differences pre- and post-ctDNA genomic profiling.
Authors: Yu Junhua , Raghav Kanwal Pratap Singh , Parikh Aparna Raj , Hanna David , Marino Enrique , Raymond Victoria M. , Nagy Rebecca , Zhang Nicole , Corcoran Ryan Bruce , Kopetz Scott , Strickler John H. , Lang Kathryn
Published: January 2021

39

Background: Clinical insights gained from real-world data have led to numerous advances in oncology including new and expanded drug approvals and an understanding of real-world clinical utilization. In this precision oncology age, integrating real-world clinical data with genomic data can lead to further advancements. We aimed to understand the genomic and treatment landscape in advanced colorectal cancer (aCRC) by leveraging a uniquely large and detailed clinical-genomic database. Methods: The GuardantINFORM (Guardant Health) database comprises aggregated commercial payer health claims and de-identified records from over 100,000 individuals with comprehensive ctDNA results (Guardant360). GuardantINFORM was queried for patients (pts) with a diagnosis of CRC. Pts with fewer than two pharmacy claims prior to or after the first ctDNA test were excluded from the regimen analysis. Latest claims data was truncated as of 8/31/2020. Results: 10,845 pts had a total of 13,510 ctDNA tests (1 – 19 tests/pt). The first ctDNA test date was from 06/2014 - 06/2020. The majority of pts had one ctDNA test (86.7%) while 5% had three or more tests. 87.9% of ctDNA tests had at least one genomic alteration identified, with the distribution of alterations consistent with prior reports (Table). 78% of pts had at least two pharmacy claims before and/or after the first ctDNA test. Of those pts with at least one CRC treatment, the most commonly prescribed CRC regimens up to one year prior to the first ctDNA test were FOLFOX +/- bevacizumab (16%, 18%), FOLFIRI +/- bevacizumab (17%, 11%), capecitabine (15%), 5-FU (12%), and regorafenib (5.2%). Anti-EGFR mono and combination therapy was reported in 6% and 16% of pts pre ctDNA testing. Immune checkpoint inhibitor (ICPi) mono and combination therapy was reported in 2% and 0.5% of pts. The most commonly prescribed CRC regimens post first ctDNA test were capecitabine (16%), FOLIRI +/- bevacizumab (15%, 13%), tipiracil and trifluridine (15%), FOLFOX +/- bevacizumab (12%, 14%), 5-FU (11%), and regorafenib (10%). Anti-EGFR mono and combination therapy was reported in 8% and 18% of pts post ctDNA testing. ICPi mono and combination therapy was reported in 5% and 1% of pts. Conclusions: Using a large and uniquely detailed clinical-genomic dataset, we produced results that replicate the observed distribution of ctDNA identified mutations present in aCRC. This genomic information combined with real-world clinical data provides valuable insights into the variety of longitudinal treatments, including before and after comprehensive ctDNA genomic profiling, allowing for detailed outcomes research, especially focused on precision oncology. [Table: see text]
Real-world study of treatment patterns and outcomes among patients with metastatic pancreatic ductal adenocarcinoma (PDAC) in Europe.
Authors: Taieb Julien , Hammel Pascal , Reni Michele , Palmer Daniel H. , Bridgewater John A. , Cubillo Antonio , Prager Gerald W. , Vermeire Alice , D'Esquermes Nathalie , Biville-Hedouin Fabienne , Teng Zhaoyang , Seufferlein Thomas , Macarulla Teresa
Published: January 2021

391

Background: Few data are available regarding real-world treatment patterns and outcomes for metastatic PDAC (mPDAC) in Europe. Methods: This retrospective, observational, chart-review study involved medical oncologists and gastroenterologists from France, Germany, Italy, Spain, and the UK. Physicians completed online patient (pt) reports for 20 consecutive pts diagnosed with PDAC between 01 and 10/2016. Here, the analysis is focused on treated pts diagnosed with mPDAC. Reports provided information on general disease and pt characteristics, diagnosis, and treatment of metastatic disease. Outcomes included median PFS and OS according to each line of metastatic therapy. In addition, how baseline performance status (PS) and treatment sequence affected OS and PFS were assessed. Results: 304 physicians (France [n=62], Germany [n=60], Italy [n=63], Spain [n=66], UK [n=53]) participated and enrolled 6,000 pts with PAC, of whom 3827 had mPDAC. Of the 3827, 3432 were treated for their metastatic disease. The most common first-line therapies were modified FOLFIRINOX (28.4%), gemcitabine + nab-paclitaxel (28.0%), and gemcitabine monotherapy (23.0%), while the most common second-line therapies were gemcitabine monotherapy (25.0%), 5-FU + oxaliplatin (21.8%), and gemcitabine + nab-paclitaxel (16.7%). The longest median PFS and OS were obtained when using mFOLFIRINOX as first-line therapy, with gemcitabine-based combinations as second-line therapy. However, pt characteristics were more favorable with FOLFIRINOX compared with the other regimens used in first line. The most common treatment in first line for patients with a worse baseline PS (PS >1) was gemcitabine monotherapy (571 patients [46%]); in addition, having a worse baseline PS was predictive of shorter survival in second line. The most common reason for discontinuation of either line was disease progression. The study showed that the choice of first- and second-line treatment among European physicians is in accordance with current ESMO guidelines; in contrast, the choice of subsequent line was more heterogeneous, according to local practices. Additional data concerning first and second line OS and PFS per treatment regimen will be presented at the meeting. Conclusions: This large real-life study highlights a clear picture of treatment patterns in European real-world clinical practice and outcomes for metastatic PDAC, which may help in more effectively managing such patients in the future. Further univariate and multivariate analysis will complete this first description.
Genomic characterization of ATM alterations in advanced pancreatic ductal adenocarcinoma (PDAC).
Authors: Perera Sheron , Denroche Robert Edward , Holter Spring , Kelly Deirdre , Zhang Amy , Wang Yifan , Dodd Anna , Ramotar Stephanie , Hutchinson Shawn , Tehfe Mustapha , Ramjeesingh Ravi , Biagi James Joseph , Wilson Julie , Notta Faiyaz , Fischer Sandra , Zogopoulos George , Grant Robert C , Gallinger Steven , Knox Jennifer J. , O'Kane Grainne M.
Published: January 2021

396

Background: BRCA1/2 and PALB2 are genes critical to the faithful repair of double strand breaks through the homologous recombination repair (HRR) pathway. Alterations in these genes serve as predictive biomarkers to both platinum and PARP inhibitors. Ataxia-telangiectasia mutated ( ATM) is also indirectly involved in HRR; however, its role as a predictive biomarker to DNA damage response agents is debated. Herein we evaluated the genomic characteristics and clinical outcomes of patients with ATM alterations on the Comprehensive Molecular Characterization of Advanced Ductal Pancreas Adenocarcinoma for Better Treatment Selection (COMPASS) trial. Methods: Patients on this study undergo a biopsy for whole genome sequencing (WGS) and RNA sequencing prior to chemotherapy; those with germline variants in ATM were reviewed by a genetics counsellor and defined as pathogenic, likely pathogenic, variant of unknown significance (VUS) or benign/likely benign. Genomic characteristics were reviewed and published classifiers of homologous recombination deficiency (HRD) were applied to all cases and included the percentage of substitution base signature (SBS) 3, the HRDetect score, the computed algorithm of large scale transitions, telomeric allelic imbalances and loss of heterozygosity (LOH), otherwise known as the genomic instability score (GIS). Results: As of January 2020, 304 patients were enrolled and 245 patients had both WGS and clinical data available. 86 germline variants in ATM were present in 70 patients. The majority of these (80%) were classified as benign or likely benign. 10 VUS were detected and 4 patients (2%) had pathogenic/likely pathogenic variants (PV). Of these 4 patients, LOH or a second somatic hit was evident in 1 case. Upon review of the PVs and VUS, SBS were consistent with typical PDAC and tumour mutational burden was low. HRDetect scores were low ( < 0.1) for 13/14 cases with either a VUS or PV; one VUS without biallelic loss, had a high HRDetect score, with presence of SBS 3 and a high GIS. This particular case was also found to have a tandem duplicator phenotype. None of the 4 cases with PV had evidence of HRD. Furthermore all four were treated with platinum based regimens without evidence of response. Conclusions: In a large series of sequenced pancreatic cancers, the presence of pathogenic germline variants in ATM was rare, with none of the cases demonstrating evidence of HRD. This suggests that this population is unlikely to benefit from PARP inhibition.
Opportunity costs of undergoing surgical resection and perioperative chemotherapy for pancreatic adenocarcinoma.
Authors: Lim Szu-Aun , Hao Scarlett , Boyd Breana , Mitsakos Anastasios , Irish William , Parikh Alexander A. , Snyder Rebecca A
Published: January 2021

398

Background: Treatment of early stage pancreatic ductal adenocarcinoma (PDAC) includes surgical resection and either neoadjuvant or adjuvant chemotherapy. Due to the intensity of treatment and perioperative morbidity rates of pancreatic resection, patients may spend a significant portion of their survival time in receipt of clinical care. However, time spent in receipt of care has not been previously described in patients with early stage PDAC. The primary aim of this study was to determine the total time spent in receipt of surgical and perioperative chemotherapy in patients with resectable PDAC. Methods: A retrospective cohort study was performed of patients diagnosed with PDAC who underwent curative-intent resection at a single institution tertiary care center between January 2015 and October 2019. Patients who died within 30 days of surgery were excluded. Total care time, including all relevant clinician visits, laboratory, radiologic and procedural studies, and treatment visits, was abstracted from the primary medical record. Care time included estimated travel time based on patient address. Care time was divided into preoperative, surgical, and systemic therapy phases of care. Time spent in surgical care included the hospital length of stay, postoperative follow-up visits, and admissions for postoperative complications. Results: A total of 86 patients were identified. Median total preoperative care time was 29 hours (IQR 11-135; 0.4% of survival time, range 0% - 72.7%). Median total time spent in surgical care was 216 hours (IQR 164-371; 2% of survival time, range 0.3% - 68.4%). Among the patients who received systemic chemotherapy care within the same institutional health system (N = 41), median total time spent in receipt of systemic therapy was 447 hours (IQR 194-647; 3% of survival time, range 0.1% - 55.4%). 10.5% of patients (N = 9) spent more than 10% of total survival time in surgical care and 5.8% (N = 5) patients spent more than 10% of survival time in receipt of systemic care. Median cumulative travel time for patients was 19 hours (IQR 10.2-37.6). Conclusions: For the majority of patients undergoing resection for PDAC, time spent in receipt of surgical care does not appear to represent a substantial time burden relative to survival time. However, for a subset of patients, the time burden is considerable. Further research to determine predictors of increased time spent in receipt of multimodality cancer care is warranted to better inform patient and surgeon communication and decision-making.
POLO: Radiologic assessment of the impact of maintenance olaparib in patients (pts) with metastatic pancreatic cancer (mPaC).
Authors: Schwartz Lawrence Howard , Kindler Hedy L. , Hammel Pascal , Reni Michele , Van Cutsem Eric , Macarulla Teresa , Hall Michael J. , Park Joon Oh , Hochhauser Daniel , Arnold Dirk , Oh Do-Youn , Reinacher-Schick Anke C. , Tortora Giampaolo , Algül Hana , O'Reilly Eileen Mary , Fromageau Jeremie , Ghiorghiu Dana C. , McGuinness David , Locker Gershon Y. , Golan Talia
Published: January 2021

412

Background: The phase III POLO study (NCT02184195) demonstrated a benefit of maintenance olaparib over placebo in the radiologically assessed primary endpoint of progression-free survival (PFS) in pts with mPaC (median 7.4 vs 3.8 months [mo]; 12-mo rate 34% vs 15%). The impact of radiologic assessment of pancreatic lesions, which is considered challenging, was explored. Methods: Tumors were assessed using Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review (BICR) in pts with mPaC treated with maintenance olaparib or placebo. PFS was analyzed in subsets of pts based on various event criteria. Results: All 154 randomized pts had mPaC prior to chemotherapy, of whom 122 had disease in the pancreas at POLO baseline (BL); 34% (53/154) had pancreas-only target lesions (TL), 26% (40/154) also had ≥1 TL outside of the pancreas, and in 19% (29/154) pancreatic disease was recorded as non-TL. Sensitivity analyses were consistent with the primary PFS analysis (Table), including when all pancreas lesion assessments were discounted (median PFS 7.4 vs 4.7 mo; 12-mo rate 38% vs 22%). Of 53 pts with pancreas-only TLs at BL, 34 had disease progression (PD); in 20 pts this was not solely based on TL measurements (16 had new lesions; 4 had multiple-cause PD). Confirmed objective responses occurred during study maintenance treatment in 20% of olaparib pts (18/92) and 10% of placebo pts (6/62). In pts with pancreas-only TLs at BL there were 7 responses in the olaparib arm (1 complete response [CR], 6 partial responses [PR]) and 2 (2 PR) in the placebo arm. In pts who had ≥1 TL outside of the pancreas at BL there were 11 (1 CR, 10 PR) and 4 (4 PR) responses, respectively. Responses were generally durable irrespective of TL location. Conclusions: The significant PFS benefit with maintenance olaparib over placebo shown in the primary analysis was consistent across all sensitivity analyses and was not impacted by radiologic assessment of pancreatic TLs. Taken together, these findings suggest that contrary to historically held belief, primary pancreas TLs may be appropriate for inclusion as sites of RECIST-evaluable disease and for assessment of treatment outcome. Clinical trial information: NCT02184195. [Table: see text]
Type of fiducial marker and clinical outcomes in stereotactic body radiation therapy for pancreatic cancer.
Authors: Baclay J Richelcyn , Minneci Madeline , Abid Dania , Toesca Diego Augusto Santos , von Eyben Rie , Pollom Erqi L. , Chang Daniel Tandel
Published: January 2021

414

Background: Stereotactic body radiation therapy (SBRT) for pancreatic cancers has been shown to improve local control, and is an important option for treatment, especially for unresectable disease. Verifying the tumor location prior to delivery of SBRT is challenging, so fiducial markers are used to track tumor location. There is currently no standard of which fiducials to use in treatment. This study would like to compare outcomes of patients treated with SBRT using different fiducial markers. Methods: Records of patients diagnosed with primary pancreas cancer who were treated with chemotherapy and SBRT were reviewed from 2006-2019. Patients were excluded if they were treated with Cyberknife, were metastatic at presentation, recurrence /persistent disease after Whipple/radiation therapy, were secondary metastatic disease (from another primary), and if they were resected after SBRT. Patients were categorized according to the fiducial used for tumor tracking during SBRT treatment: gold seeds, intrabiliary stent, or both. Cumulative incidence of local recurrence (CIR) was analyzed with death as competing event, and time to over-all survival was estimated using Kaplan-Meier curves. Results: A total of 129 patients with available fiducial information were included in this study, of which 64 (49.6%) were treated with SBRT using gold seeds, 23 (17.8%) using intrabiliary stent, and 42 (32.6%) using both the seeds and stent. There were no difference between groups in terms of baseline characteristics such as age (p = 0.169), sex (p = 0.293), and stage grouping (p = 0.293). Median follow-up time was 15 months (range: 0.3-37.3 months). The 6- and 12-month CIR were 1.5% (95%CI, 0.1%-7.4%) and 11% (95%CI, 4.8%-20.2%) for patients treated with seeds, 4.3% (95%CI, 0.2%-18.6%) and 30.4% (95%CI, 13.1%-49.8%) for patients treated with stent, and 4.8% (95%CI, 0.8%-14.6%) and 19.5% (95%CI, 9.0%-32.9%) for patients treated with both (p = 0.007). Median time to overall survival was 15.3 months (95%CI, 13-17.8 months) for patients treated with seeds, 21.3 months (95%CI, 14.7-29.6 months) for patients treated with stent, and 15.7 months (95%CI, 11.5-19.7 months) for patients treated with both (p = 0.307). Univariate analysis for predictors of local failure did not show significance for age (p = 0.812), or advanced stage (p = 0.483), but was significant for the presence of seeds (p = 0.006). Conclusions: The type of fiducial marker used for tracking during pancreas SBRT treatment was associated with local failure but no difference in overall survival. Further analysis is warranted to see which clinical factors contribute to this difference.
Evaluating the intratumor microbiome of pancreatic ductal adenocarcinoma (PDAC) by analyzing the fresh frozen tissues obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA).
Authors: Nakano Shintaro , Kawamoto Yasuyuki , Harada Kazuaki , Yuki Satoshi , Ito Ken , Saitoh Rika , Yamamura Takahiro , Hirata Hajime , Takishin Yunosuke , Furukawa Ryutaro , Nagai Kousuke , Kuwatani Masaki , Komatsu Yoshito , Sakamoto Naoya
Published: January 2021

418

Background: Recent studies implied that intratumor microbiome was associated with carciniogenesis, development, prognosis and chemoresistance of pancreatic cancer (PC). There was more abundant bacteria in tumor tissue of pancreatic cancer than that of healthy controls. In clinical setting, diversity of intratumor bacteria was associated with good outcome of patients with resected pancreatic cancer. Specific intratumor bacteria could inactivate gemcitabine, which is crucial drug for PDAC, and may contribute to the resistance of gemcitabine.While most previous studies analyzed intratumor bacteria in PC by using resected tumor tissues, it was often impossible to obtain tumor sample from unresectable advanced PC. In addition, it is unclear whether tiny tissue obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is useful for analyzing intratumor microbiome.Therefore, we planned to evaluate the intratumor microbiome by analyzing the sample from EUS-FNA. Methods: This study was carried out as a single center, prospective observational study. The patients with PC were eligible for this study. PC tissues were collected from patients who undergo EUS-FNA. Biopsy tissues from the duodenal and gastric mucosa were also collected from the same patients. All samples were immediately stored at -80°C until use. Bacterial DNA was extracted from these specimens and 16S rRNA sequencing was performed. The endpoints of this study were success rate of detecting intratumor bacteria and association between intratumor bacteria and bacteria on the duodenal or gastric mucosa. Results: A total of 90 tissue samples from 30 patients were collected. The median age was 70 years (range 54-86 years), 19/5/6 patients had pancreatic head/body/tail tumor, 16s rRNA sequencing analyses showed that 24 samples (80%) of FNA from pancreatic tumor, 30 samples (100%) of gastric mucosa and 29 samples (97%) of duodenum mucosa could be analyzed. In diversity analyses, PC showed a lower alpha diversity compared to gastric or duodenum tissue. There was a significant difference in microbial structure between PC and duodenum tissue. In PC, dominant phylum was Proteobacteria and dominant genus was Acinetobacter. Conclusions: PC tissues obtained by EUS-FNA were useful for analyzing intratumor microbiome.
Mutational profile analysis and related outcomes in primary and metastatic pancreatic cancer (PC).
Authors: Rohatgi Abhinav , Desai Aveena , Hindenburg Alexander A.
Published: January 2021

427

Background: PC has not been well molecularly characterized and there is an unmet need in our understanding of the biological properties of PC. One previous study has found that the presence of CDKN2A mutations is an independent negative prognostic OS indicator. We evaluated molecular analysis on tumor specimens to determine whether increased mutational burden affects survival. Methods: PDAC samples from patients seen at the NYU Perlmutter Cancer Center at Winthrop Oncology Hematology Associates between 2015-2020 were profiled using next generation sequencing through Foundation Cdx. Genomic data was correlated with mined clinical data. Pt outcomes were correlated with the presence of mutations defined in 3 categories: 3 or less mutations, 4 mutations, 5 or more mutations. Results: Our cohort (N = 81) included 42% men and 58% women. 55% percent had primary (localized and locally advanced) disease and 44% had stage IV disease. Genetic mutations were most commonly found in KRAS, CDKN2A, TP53, NOTCH, SMAD4. Mutations seen less frequently were BRAF, HER2, RB1, ARID1A, MTAP, MLL, BRCA2. 43% of pts had 3 or less mutations, 15% 4 mutations, 42% had 5 or more mutations. There was no difference in number of mutations present between primary vs metastatic cancers. Median PFS was 13.5 months and overall survival (OS) for all pts was 20.0 months. The OS in primary group was 26.1 mos while it was 12.4 mos in the metastatic group. Patients with 5+ mutations had a 1.5 mos decreased OS and a 10% decreased 24-mos OS%. When stratified by primary (localized) disease, there was an 8.3 mos decrease in the 5+ mutation group vs 3 mutation group. When stratified by metastatic disease at diagnosis, there was no appreciable difference in OS between mutational groups. Conclusions: In the primary PC cohort, increasing burden of gene alteration patterns from 3 to 5+ mutations is correlated with decreased overall survival. The effect did not extend to the metastatic group likely due to disease burden driving survival whereas in primary PC group, survival reflected the tumor biology. This suggests that as additional carcinogenic pathways (DNA repair, growth, apoptosis) are mutated, tumor biology becomes more aggressive. This study provides an impetus for mutational profiling in early stage pancreatic cancer. These findings can contribute to the use of molecular profiles for prognostication and further development of targeted therapies. [Table: see text]
Evaluating the clinical impact of primary tumor location in pancreatic adenocarcinoma.
Authors: Carhart Randi Zukas , Micaily Ida , Fratamico Roberto Stefan , Daskalakis Constantine , Lam Sophia , Cohen Steven J. , Basu Mallick Atrayee
Published: January 2021

428

Background: Pancreatic adenocarcinoma is the fourth most common cause of cancer-related death in the US. The location of the primary lesion has long been thought to influence survival due to differences in time to presentation and ability to undergo cancer directed surgery. We hypothesized that patients with tumors arising in the body or tail (distal) would have poorer survival than patients who presented with lesions in the head of the pancreas (proximal) and that this difference would be true regardless of stage at diagnosis due in part to other factors such as intrinsic differences in the biology of these tumor types. A retrospective chart review at a single center with a high volume of pancreatic cancer directed surgery was carried out to address this question. Methods: Institution database was queried to identify patients with the ICD9 diagnosis of pancreatic adenocarcinoma of the head, body, and tail between 2014-2017; the inclusion criteria were 18 years or older, biopsy proven adenocarcinoma and a single mass in the pancreas at presentation. A total of 907 entries were screened with 324 patients being analyzed (236 proximal and 88 distal). CDC National Death Index registry and obituary reports were utilized to determine official dates of death. Results: Overall median survival was statistically higher in the proximal group than the distal group 16.0 vs 11.2 months (p=0.015). However, there was no significant difference in survival by stage of the proximal group over the distal group with stage I/II in the proximal group surviving 21 months versus distal 25.7 months, p=0.436; stage III, proximal surviving 11.7 months versus distal 18.0 months, p=0.393; stage IV, proximal surviving 6.5 months versus distal 4.9 months, p=0.675. The distal group was more likely to be metastatic on diagnosis (59% versus 18%) and was less likely to undergo surgery (34% vs 50%). In the surgical group, there was similar survival of 24.6 months in the proximal group versus 19.4 distal (p=0.795). Conclusions: Patients in the proximal group had a higher overall survival than the distal group as expected. Overall, however, when broken down by stage or surgery, the difference in survival between the proximal and distal groups was minimal with Hazard Ratio 0.96 (95%, CI=0.7, 1.30). Therefore, early stage diagnosis or surgery strongly account for the survival benefit in the proximal population rather than other factors like an intrinsic difference in the nature of the tumors themselves.
Significant lipid and neutrophil accumulation and active inflammasome in high BMI tumor regions of human pancreatic ductal adenocarcinoma.
Authors: Khattab Ahmed , Patruni Sunita , Garciafigueroa Yesica , Phillips Brett , Engman Carl , Khatoon Nazia , Shankar Karthik , Rizvi Ali , Miller Stacey , Giannoukakis Nick , Monga Dulabh K.
Published: January 2021

438

Background: Obesity is an established risk factor for cancer and cancer-related mortality. Adipocytes may act as a “damage” signal resulting in the accumulation of innate immune cells, fueling an inflammatory micro-environment. Among the innate immune cells, tumor-associated neutrophils (TANs) are confirmed to accumulate inside the tumor. As obesity is a significant risk factor for a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), we hypothesize that obesity-driven adipose fuels the progression of PDAC in a TAN and inflammasome-facilitated manner. This may happen through several mechanisms, including genomic instability of aggressive PDAC clonal populations. Methods: Tissue from resected tumors of PDAC patients (n = 44) with a body-mass index (BMI) > 27 (obese [n = 21]) and BMI < 22 (normal [n = 23]) were incubated with anti-human CD66b antibodies and detected using standard immunofluorescent microscopy techniques. Images were acquired in a Zeiss Axioplan microscope workstation and analyzed by ZEN and Metamorph software. Results: We identified the presence of adipocytes in all tissue sections and CD66b+ neutrophils in all tissue sections of normal BMI patients and in 81% of high BMI patients. There is a significantly greater density of adipocytes in the tumor environment when compared to adjacent normal areas, suggesting that these cells are acting as a damage signal. Our novel data also shows that high BMI results in a significantly higher neutrophil count in tumor specific tissue when compared to patients with a low BMI. These data suggest an association between BMI and inflammasome accumulation in the tumor environment. Conclusions: Our data uniquely shows that CD66b+ neutrophils tend to accumulate inside PDAC in high BMI patients and this is associated with intra-tumoral active inflammasomes. The higher concentrations of these inflammasomes in higher BMI patients may be of mechanistic relevance in understanding how inflammation induces progression of PDAC. A larger cohort of tissues from PDAC obtained from low and high BMI individuals will be needed to test our hypothesis and to begin to decipher the role of obesity on inflammation and PDAC progression.