bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extent of lymph node resection and effect on pancreatic cancer overall survival.
Authors: Cox Brian , Manguso Nicholas , Quadri Humair , Crystal Jessica , Atkins Katelyn Mae , Lee Jaewon , Hendifar Andrew Eugene , Kamrava Mitchell , Tuli Richard , Gong Jun , Gangi Alexandra 
Published: February 2020

682 Background: Lymph node (LN) metastases affect overall survival (OS) in pancreatic cancer (PC). However, a LN sampling threshold does not exist. We examined the impact of nodal sampling on overall survival (OS). Methods: Patients with Stage I-III PC ≥55 years old who underwent curative resection from 2004-2016 were identified from the National Cancer Database (NCDB). After adjusting for age, gender, grade, stage, and Charlson-Deyo score, multiple binomial logistic regression analyses assessed the impact of the LN ratio (LNR) on OS. LNR was defined as the number of positive LN over the number of LN examined. Regression analyses, a Cox-Regression, and a Kaplan-Meier survival curve assessed how many LN should be sampled. Results: A total of 13,673 patients, median age 69 years (55-90), were included. Most were Caucasian (86.6%) males with Charlson-Deyo scores ≤ 1 (90.3%) and moderately to poorly differentiated PC (90.1%). Median number of LN examined was 15 (1-75) with a median of 1 positive LN (0-35). As expected, increased number of positive LNs was associated with reduced OS, p < 0.001. After data normalization, an increasing LNR was associated with a 12-fold likelihood of death [OR: 11.9, p < 0.001 (CI 6.0, 23.7)]. Subsequent regression models established evaluation of ≥ 16 LNs as the greatest predictor of OS. A regression model evaluating < or ≥ 16 lymph nodes was performed to ascertain the effects of age, gender, ethnicity, grade, stage, and LN examined on OS. The logistic regression model correctly classified 74.5% of cases with a specificity of 99.6% (p < 0.001). Examination of < 16 LN, Caucasian race, grade, stage, and higher Charlson-Deyo scores were significantly associated with decreased OS. If ≥ 16 LNs were examined, patients had a 1.5-fold likelihood of better OS, p < 0.001 (CI 1.4, 1.6). An adjusted Cox Regression showed increased HR of 1.2, p < 0.001 (CI 1.1, 1.2) and an unadjusted Kaplan Meier survival curve predicted ≥ 16 LN examined are associated with an increase in OS of 2.8 months [log-rank: 32.0, p < 0.001]. Conclusions: Patients undergoing curative intent resection for PC should have adequate nodal sampling. Stratification of patients by LNR may provide useful information of OS. Examination of ≥ 16 LNs impacts OS in patients with Stage I-III PC.
Goals of care designations in advanced pancreatic cancer patients undergoing palliative chemotherapy.
Authors: Anaka Matthew , Lee Minji , Lim Elisa , Ghosh Sunita , Cheung Winson Y. , Spratlin Jennifer L. 
Published: February 2020

683 Background: Discussion of goals of care (GoC) is a key part of quality care for patients with palliative cancer. Numerous studies have shown that documentation of GoC in this population remains low. In 2014, Alberta Health Services launched a health-system wide initiative to provide patients with physical copies of their GoC designation intended to be available at all health-system interactions. Here we describe rates of GoC documentation in the period surrounding this initiative. Methods: This is a retrospective cohort analysis of 240 patients with locally advanced or metastatic pancreatic cancer treated with palliative chemotherapy from 2012-2015 in Alberta, Canada. Data were obtained from outpatient electronic medical record documentation and the provincial cancer registry. Results: 63.8% (153/240) of patients had a documented GoC discussion, with 60.4% (145/240) receiving a specific GoC designation. 59.6% (143/240) of patients were referred to palliative care, with 32.5% (78/240) seen by palliative care physician. Of 334 individual GoC discussions documented, 38.6% (129/334) were by medical oncologists, 2.3% (10/334) were by radiation oncologists, 27.2% (91/334) were by palliative care, and 19.2% (64/334) were by other inpatient physicians during hospital admissions. At least 9.6% (32/334) referenced discussions that occurred prior to initial consultation with an oncology physician. Conclusions: The majority of pancreatic cancer patients undergoing palliative chemotherapy had a documented GoC designation during the study period. Providing patients with physical copies of their GoC designation may therefore represent a simple but effective means of increasing GoC documentation in the outpatient oncology setting.
Risk factors for severe neutropenia among pancreatic cancer patients receiving nab-paclitaxel and gemcitabine combination therapy.
Authors: Kawakami Kazuyoshi , Ito Genta , Aoyama Takeshi , Yokokawa Takashi , Nakamura Masashi , Ozaka Masato , Sasahira Naoki , Kizaki Hayato , Hashiguchi Masayuki , Hama Toshihiro , Hori Satoko 
Published: February 2020

684 Background: Albumin-bound paclitaxel (nab-paclitaxel) and gemcitabine combination therapy (GnP therapy) significantly extends overall survival in patients with metastatic pancreatic cancer, compared to conventional gemcitabine monotherapy. However, severe neutropenia (Grade ≥ 3) occurred in 67.6% of patients in the Japanese phase I/II trials of GnP therapy, and is often a limiting factor. The purpose of this study was to identify the risk factors for severe neutropenia in pancreatic patients receiving GnP therapy in clinical settings. Methods: A retrospective study of 222 consecutive patients with pancreatic cancer who received GnP therapy at the Cancer Institute Hospital from December 2014 to December 2016 was conducted. Univariate and multivariate analyses were used to compare blood test values and patients’ characteristics between patients with no neutropenia or Grade 1/2 (non-serious) neutropenia and those with Grade ≥ 3 (severe) neutropenia. Results: There were 19 patients (8.6%) with modified FOLFIRINOX in the previous treatment history. The median doses of nab-paclitaxel and gemcitabine were 192.5 mg (range 134-277.5) and 1,545 mg (range 1,000-2,220), respectively. Severe neutropenia and febrile neutropenia occurred in 118 patients (53.2%) and 15 patients (6.8%), respectively. Multivariate logistic regression analysis indicated that ANC (absolute neutrophil count) < 3.03 x 103 /μL (OR: 4.806, 95% CI: 2.416-9.558, p = 0.000), T-Bil ≥ 0.6 mg/dl (OR: 1.964, 95% CI: 1.040-3.708, p = 0.037) and CRP < 0.13 mg/dl (OR: 2.607, 95% CI: 1.331-5.106, p = 0.005) were significant risk factors for severe neutropenia. The incidence rate of severe neutropenia was 85.7% (18/21) in patients with all three identified factors, while it was 27.7% (13/47) in patients with none of them. Age was not a risk factor in either univariate or multivariate analysis. Conclusions: Low ANC, high T-Bil, and low CRP were found to be risk factors for severe neutropenia in patients receiving GnP therapy. It would be desirable to monitor patients with these risk factors carefully, even if their values are within the standard ranges.
Adverse events (AEs) with maintenance olaparib in patients with a germline BRCA mutation (gBRCAm) and metastatic pancreatic cancer (mPaC): Phase III POLO trial.
Authors: Reni Michele , Kindler Hedy L. , Hammel Pascal , 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 , McGuinness David , Cui Karen , Schlienger Katia , Locker Gershon Y. , Golan Talia 
Published: February 2020

686 Background: In POLO (NCT02184195), maintenance olaparib was well tolerated and led to a significant progression-free survival benefit vs placebo in patients with a gBRCAm and mPaC whose disease had not progressed on first-line platinum-based chemotherapy (HR 0.53; 95% CI 0.35–0.82) (Golan et al. NEJM 2019). We analyzed common AEs and their management in POLO. Methods: Patients were randomized (3:2) to maintenance olaparib (tablets; 300 mg bid) or placebo until disease progression or unacceptable toxicity. AEs were graded using CTCAE v4.0. Results: Of 154 randomized patients, 151 were treated (olaparib, n=91; placebo, n=60) and included in safety analyses. Median treatment duration was 6.0 months (m) for olaparib and 3.7 m for placebo. Management of fatigue/asthenia, nausea, anemia and vomiting included supportive treatment and/or dose modification; few patients discontinued treatment due to AEs (Table). Of patients with anemia, 14 olaparib recipients received a blood transfusion while on study treatment; one olaparib recipient received epoetin beta. Conclusions: The AE profile of maintenance olaparib in patients with a gBRCAm and mPaC was consistent with that seen in other tumor types.Common AEs of fatigue/asthenia, nausea, anemia and vomiting occurred early, were manageable and led to few treatment discontinuations. Clinical trial information: NCT02184195 . [Table: see text]
Outcomes of advanced gastrointestinal (GI) cancer patients in relationship to opioid use: An individual patient data pooled analysis from eight clinical trials.
Authors: Abdel-Rahman Omar , Karachiwala Hatim , Easaw Jacob C. 
Published: February 2020

687 Background: The current study aims at assessing the patterns of opioid use, and evaluating the impact of opioid use on survival outcomes among patients with advanced GI cancers who were included in eight clinical trials. Methods: De-identified datasets of eight clinical trials evaluating first-line systemic treatment for advanced GI cancers (NCT01124786; NCT00844649; NCT00290966; NCT00678535; NCT00699374; NCT00272051; NCT00305188; NCT00384176) were accessed from the Project Data Sphere platform. These trials evaluated patients with pancreatic, gastric, hepatocellular and colorectal carcinoma. Multivariable logistic regression analysis was used to evaluate factors predicting the use of opioids. Kaplan-Meier survival estimates were used to compare survival outcomes in each disease entity among patients who did or did not receive opioid treatment. Multivariable Cox regression analysis was used to assess the impact of opioid use on survival outcomes in each disease entity. Results: A total of 3441 participants were included in the current analysis. The following factors predicted a higher probability of opioid use within logistic regression analysis: younger age (P = 0.004), non-white race (P = 0.010), higher ECOG score (P < 0.001) and pancreatic primary site (P < 0.001). Use of opioids was consistently associated with worse overall survival in Kaplan-Meier survival estimates of each disease entity (for pancreatic cancer: P = 0.008; for gastric cancer: P < 0.001; for hepatocellular carcinoma: P < 0.001 and for colorectal cancer: P < 0.001). Within multivariable Cox regression analysis, opioid use was associated with worse overall survival among patients with pancreatic cancer (HR = 1.245; 95% CI: 1.063-1.459; P = 0.007), gastric cancer (HR = 1.725; 95% CI: 1.403-2.122; P < 0.001), hepatocellular carcinoma (HR = 1.841; 95 CI: 1.480-2.290; P < 0.001) and colorectal cancer (HR = 1.651; 95% CI: 1.380-1.975; P < 0.001). Conclusions: Opioid use is consistently associated with worse overall survival among patients with different GI cancers. Further studies are needed to evaluate the underlying mechanisms of this observation.
An exploratory study of metformin (Met) with or without rapamycin (Rapa) as maintenance therapy after induction chemotherapy in patients (Pts) with metastatic pancreatic adenocarcinoma (PDA).
Authors: Bever Katherine M. , Borazanci Erkut Hasan , Thompson Elizabeth , Wu Annie , Durham Jennifer N. , Liu Meizheng , Wilt Cara , Fu Wei , Leal Jeffrey P. , De Jesus-Acosta Ana , Wang Hao , Cosgrove David , Zheng Lei , Laheru Daniel A. , Von Hoff Daniel D. , Jaffee Elizabeth M. , Powell Jonathan , Le Dung T. 
Published: February 2020

700 Background: Few studies have examined maintenance therapy in unselected pts with metastatic PDA (mPDA). mTOR signaling is central to several oncogenic pathways in PDA and also has a role in T cell differentiation and activation, and we hypothesized a role for mTOR inhibition (mTORi) in the maintenance setting. Methods: This was a randomized open-label study conducted at 2 sites. Eligible pts had mPDA with stable disease for ≥6 months on chemotherapy and ECOG PS 0/1. Pts were randomized 1:1 to Met 850mg BID alone (Arm A) or with Rapa 4mg daily (Arm B), stratified by prior FOLFIRINOX. Baseline and on-treatment PET scans and peripheral blood mononuclear cells were obtained for exploratory analyses. Results: 23 pts were randomized. Median age was 64 (range 34-77) and 82% had ECOG PS 1. 12 of 23 received prior FOLFIRINOX; 8 received >1 prior line of therapy. 22 subjects (11 per arm) were treated per protocol. Treatment related adverse events of Grade ≥3 were seen in 0% vs 27% of pts in Arm A vs B and were all asymptomatic hematologic or electrolyte abnormalities that were not clinically significant. Median PFS/OS were 3.5 (95% CI: 2.9-9.2)/13.2 mos (95% CI: 7.8 to not reached) respectively, with 2 yr OS rate of 37% (95% CI: 21-66%); there were no differences between treatment arms. As expected in the maximally debulked setting, no responses were observed by RECIST; however, decreases in FDG avidity and/or CA199 were observed in several long-term survivors. Better survival was associated with low baseline neutrophil to lymphocyte ratio, baseline lack of assessable disease by PET, and with expansion of dendritic cells following treatment. Compared to Met alone, Met + Rapa was associated with decreased mTOR activity on some immune cell subsets and decreased metabolic fitness, but this was not correlated with outcome. Conclusions: Met +/- rapa maintenance for mPDA was well-tolerated and several pts achieved stable disease associated with exceptionally long survival. Further prospective studies are needed to clarify the role of mTORi in the maintenance setting and to enhance pt selection for such approaches. Clinical trial information: NCT02048384.
Single institutional analysis of resectable pancreatic cancer.
Authors: Wiisanen Jeff , Navin Patrick , El Khatib Moustafa , Bamlet William R , Cleary Sean P. , McWilliams Robert R. , Truty Mark J. , Ho Thanh P. , Hartgers Mindy L. , Yadav Siddhartha , Mahipal Amit 
Published: February 2020

706 Background: In recent years, there has been a shift towards neo-adjuvant treatment (NAT) of non-metastatic pancreas cancer in the hopes of improving negative margin rate, lymph node negativity, recurrence and survival. Even patients deemed resectable based on NCCN criteria are receiving NAT but data for these patients remains limited. This current study evaluated the outcomes of patients diagnosed with resectable pancreatic adenocarcinoma. Methods: Patients were retrospectively identified through the Mayo Clinic, Rochester SPORE pancreatic cancer registry as well as search of the electronic medical record via Advanced Cohort Explorer from May 2011 to 2016. Baseline demographics, tumor characteristics, treatments rendered, and outcomes were collected. Variables were analyzed for association with recurrence from time of surgery and survival from time of diagnosis using Kaplan-Meier curves and Cox proportional hazards regression. Results: A total of 520 patients with resectable pancreatic adenocarcinoma were identified. 72 patients received upfront chemotherapy with 44 (61.1%) proceeding to surgical resection. 62 patients received upfront chemotherapy followed by radiation with 33 (53.2%) proceeding to surgical resection. 12 patients received upfront radiation alone with 7 (58.3%) proceeding to surgical resection. 374 patients did not receive any NAT with 293 (78.3%) proceeding to surgical resection. In total, 377 (72.5%) went to resection. Median time to recurrence from surgery was 27.7 months vs. 21.7 months for NAT and upfront resection, respectively (HR 0.87, 95% CI 0.60-1.72, p = 0.48). Median overall survival from diagnosis for those receiving NAT was 40.6 months vs. 24.7 months for those receiving upfront resection (HR 0.62, 95% CI 0.41-0.92, p = 0.02). Conclusions: This study shows an approximate 16 month improvement in overall survival of patients receiving upfront NAT for resectable pancreatic adenocarcinoma. This might be due to a better selection of patients. It also highlights that not all patients with resectable cancer undergo resection. Further studies are warranted to identify why resectable patients are not proceeding to resection and which specific NAT approaches benefit patients the most.
Pancreatic ductal adenocarcinoma (PDAC), BRCA: Detailed analysis and outcomes of cohort from Memorial Sloan Kettering Cancer Center (MSK).
Authors: Momtaz Parisa , O'Connor Catherine Anne , Chou Joanne F. , Capanu Marinela , Yu Kenneth H. , Varghese Anna M. , Park Wungki , Zervoudakis Alice , Li Jia , Ku Geoffrey Yuyat , Reidy Diane Lauren , Shcherba Marina , Harding James J. , Goldberg Zoe , Abou-Alfa Ghassan K. , Stadler Zsofia Kinga , Salo-Mullen Erin E. , O'Reilly Eileen Mary 
Published: February 2020

708 Background: Given encouraging responses of platinum agents and poly-ADP ribose polymerase inhibitors (PARPi) in BRCA mutated (mut) PDAC, we sought to identify patients (pts) with BRCA mut PDAC treated at MSKCC and to evaluate outcome. Methods: Institutional database at MSK with IRB approval was queried for PDAC germline (g) or somatic (s) BRCA1/2 mut. Genomic profiling, clinicopathologic characteristics and outcomes were collected. Overall survival (OS) from diagnosis was estimated using Kaplan-Meier method. Results: n = 126 with BRCA1/2 mut PDAC were identified between 1/2011-12/2018. n = 77 (61%) male and median age of 62 (range 24-85) at diagnosis. n = 78 (62%) had g BRCA mut (n = 21 BRCA1; n = 57 BRCA2). n = 54 (43%) had a family history of BRCA-related malignancies; 35pts (28%) with a personal history of other BRCA-associated malignancy. n = 66 (52%) AJCC stage IV; of these 43pts (65%) received platinum-based therapy with a partial response (PR) in 35pts (81%); median duration 7 months (m) (range 0.5-39m). n = 40 (32%) received ≥ 4 lines of therapy (range 1-6 lines). n = 44 (35%) received PARPi and 11% (n = 14) received immunotherapy. Median OS for the entire cohort 32.1 m (95% CI 23.9, 42.6). Median OS for stage I-II 49.9m (95% CI 38.5,-); stage III 43m (95% CI 33.9,-) and stage IV 19.1m (95% CI 19.1 16.1,25.8). We did not observe a statistically significant difference in OS between BRCA1 vs BRCA2 pts. Conclusions: BRCA mut PDAC constitutes a small but likely distinct biologic subgroup. Improved OS was notable relative to historical data, possibly due to the integration of platinum and PARPi therapy and possibly due to contribution from disease biology. [Table: see text]
Clinical outcome of initially unresectable pancreatic cancer patients: Conversion surgery after modified FOLFIRINOX or gemcitabine nab-paclitaxel.
Authors: Ushida Yuta , Inoue Yosuke , Ito Hiromichi , Ono Yoshihiro , Sato Takafumi , Takahashi Yu 
Published: February 2020

725 Background: Although pancreatic cancer (PC) is unfavorable clinical entity, the prognosis of resectable PC has been improving due to perioperative chemotherapy. Meanwhile, the prognosis of unresectable (UR) PC remains poor. In highly selected patients, however, conversion surgery (CS) has been performed with good outcome. Indication criteria of CS remain unestablished because the number of patients who underwent CS was very small in each institution. Methods: From 2014 to 2018, 485 consecutive patients with UR-PC who received modified FOLFIRINOX (mFFX) / Gemcitabine Nab-Paclitaxel (GnP) chemotherapy were reviewed. Among them, patients with disease control for more than 8 months were enrolled and divided into two groups; patients who underwent CS (CS group) and patients who did not undergo CS (non-CS group). We compared clinical characteristics and survival outcomes between groups. Our surgical indications were as follows: 1) Decreasing trend in CA19-9, 2) With response for chemotherapy in image, 3) Disease control more than 8 months, 4) Decision in Cancer board as for metastatic cases. Results: In UR-PC patients, 358 patients had distant metastasis (MPC) and 127 patients had locally advanced (LA) PC. The overall survival (OS), progression free survival (PFS) and conversion rate of LAPC were significantly better than MPC (OS; 21 vs. 13 months, PFS; 12 vs. 7 months, Conversion rate; 16 vs. 5 %, p < 0.001). Chemotherapy regimen (mFFX/GnP) had no significant difference in survival outcome. Between CS group (n = 39) with non-CS group (n = 160), age, sex, body mass index, location of lesion, CEA, CA19-9, regimen of chemotherapy and histology had no significant differences. The median survival time of CS group was significantly better than that of non-CS group (OS; NA vs. 21 months, p < 0.001, PFS; 24 vs. 14 months, p = 0.01). In CS group, median operative duration was 509 minutes, blood loss was 735 ml, hospital stay was 26 days, and there was no 90-days mortality case. Conclusions: In our retrospective study, CS for UR-PC can be safely performed, and among carefully selected patients, reasonable short and long term outcomes can be obtained without acceptable morbidity rate.
Establishment of patient-derived tumor xenograft (PDX) model as artificially-created liver metastasis using cryopreserved pancreatic ductal adenocarcinoma.
Authors: Kimura Kenjiro , Tanaka Ryota , Amano Ryosuke , Kubo Shoji , Tanaka Hiroaki , Muguruma Kazuya , Hirakawa Kosei , Ohira Masaichi 
Published: February 2020

729 Background: Translational research using patient-derived tumor xenograft (PDX) model is progressing rapidly, and is also becoming widespread in pancreatic cancer research. The purpose of this study was to establish the liver transplant PDX model as artificially-created liver metastasis with cryopreserved primary pancreatic ductal adenocarcinoma(PDAC). Methods: The primary PDAC from 10 patients were cryopreserved and transplanted into NSG mice using liver pocket method. For engraftment and similarity evaluation, H&E staining and immunohistochemical staining such as Ki-67, p53, SMAD4, and MUC1 were performed. Results: Patient-derived xenograft was succeeded in 6 cases (60%), 10 mice (33.3%). Ki-67 index of primary PDAC and the interval of cryopreservation were significantly related to successful engraftment, respectively (p = 0.003, p = 0.007). Conclusions: In this study, we succeeded in establishing a liver transplant PDX mouse model as a preclinical platform. The factors such as Ki-67 index and the interval of cryopreservation would affect the successful establishment.