bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in overall survival for patients with cholangiocarcinoma: Racial/ethnic disparity or socioeconomic factors?
Authors: Lee Rachel M , Liu Yuan , Zaidi Mohammad Yahya , Gamboa Adriana Carolina , Russell Maria C. , Cardona Kenneth , Maithel Shishir K. 
Published: January 2019

380 Background: Inequities in cancer survival are well documented. Whether disparities in overall survival (OS) result from inherent racial differences in underlying disease biology or socioeconomic factors (SEF) is not known. Our aim was to define the association of race/ethnicity and SEF with OS in pts with cholangiocarcinoma (CCA). Methods: Pts with CCA of all sites and stages in the National Cancer Data Base (2004-14) were included. Racial/ethnic groups were defined as non-Hispanic White (NH-W), non-Hispanic Black (NH-B), Asian, and Hispanic. Income and education were based on census data for pts’ zip code. Income was defined as high (³$63,000) vs low ( < $63,000). Primary outcome was OS. Results: 27,151 pts were included with a mean age of 68 yrs; 51% were male. 78% were NH-W, 8% NH-B, 6% Asian, and 6% Hispanic. 56% had Medicare, 33% private insurance, 7% Medicaid, and 4% were uninsured. 67% had high income. 21% lived in an area where > 20% of adults did not finish high school. NH-B and Hispanic pts had more unfavorable SEF including uninsured status, low income, and less formal education than NH-W and Asian pts (all p < 0.001). They were also younger, more likely to be female and to have metastatic disease (all p < 0.001). Despite this, NH-B race and Hispanic ethnicity were not associated with decreased OS. Male sex, older age, non-private insurance, low income, lower education, non-academic facility, location outside the Northeast, higher Charlson-Deyo score, worse grade, larger tumor size, and higher stage were all associated with decreased OS (all p < 0.001). On MV analysis, along with adverse pathologic factors, type of insurance (p = 0.003), low income (p < 0.001), and facility type and location of treatment (p < 0.001) remained associated with decreased OS; non-white race/ethnicity was not. Conclusions: Disparities in survival exist in CCA, however they are not driven by race/ethnicity. Non-privately insured and low-income pts had decreased OS, as did pts treated at non-academic centers and outside the Northeast. This suggests that decreased ability to access and afford care results in worse outcomes, rather than biological differences amongst racial/ethnic groups.
Gemcitabine, docetaxel, and capecitabine (GTX) as a first-line regimen in metastatic pancreatic adenocarcinomas (mPAC): A single institution experience.
Authors: Singh Vikas , Sharma Vivek R. 
Published: January 2019

385 Background: After decades of minimal to no therapeutic options, Gemcitabine emerged as the only safe & effective frontline regimen for mPAC. A 3-drug combination regimen, GTX, first optimized by Fine et al in 2009 showed improved progression free (PFS) & median overall survival (mOS) based on a multicentric prospective phase II study. It didn’t receive much wider acceptance likely due to lack of phase III data and emergence of newer regimens such as Gemcitabine plus nab-Paclitaxel (GA) and FOLFIRINOX (FFX). We reviewed our institutions experience with GTX and other regimens in mPAC patients. Methods: We performed a retrospective review of clinical outcomes in patients diagnosed with mPAC between January 2005 and December 2015 and treated at our institution. Attempts were made to include all eligible patients to reduce any selection bias. Results: Fifty patients with mPAC were analyzed for mOS and toxicities with different regimens. 50% patients received GTX while remaining received – FFX (22%), Gemcitabine (14%), GA (4%), FOLFOX (4%) & other (6%) regimens. The mOS for all the patients was 7.67 months (95% CI 5.98-10.81). The mOS was significantly improved in patients who received GTX as first line regimen compared to patients who received non-GTX regimens (9.45 vs 6.08 months; P-0.0157). GTX also showed non-statistically significant improvement in mOS compared to FFX (9.45 vs 6.08 months; P-0.1436). Compared with FFX, GTX was associated with fewer severe GI (40 vs 45.5%; p – 1.00) and hematologic (20 vs 36.4%; p – 0.40) toxicities. Conclusions: GTX significantly improved mOS and had fewer severe toxicities compared to non-GTX regimens. Limitations include the retrospective and non-randomized nature of the study and the small sample size. However, GTX may be considered an alternative first line regimen in mPAC patients who are unable to tolerate aggressive regimens such as FFX and in whom the need to balance quality of life with efficacy is particularly important.
Combination of everolimus and lu-177 PRRT in treatment of G1-2 neuroendocrine tumors (NET): Phase 1-2 study.
Authors: Aljubran Ali Husain , Alrowaili Mohamed , Raef Hussein , Bazarbashi Shouki , Alzahrani Ahmed M , Almuhaideb Ahmed , Almanea Hadeel , Badran Ahmed ali , Al-Dalee Abdelmuniem , Tuli Mahmoud 
Published: January 2019

386 Background: Everolimus and Lutetium-177 PRRT were approved as monotherapy. However, animal model research showed synergistic effect of the combination. The goal of this study is to assess the safety and efficacy of the combination in treatment of unresectable G1-2 NETs of all gastrointestinal, lung and pancreatic origins. Methods: This is a phase 1-2 study. Phase 1 part involves finding the maximum tolerating dose (MTD) of everolimus and accordingly to recommend dose for phase II part. Starting everolimus dose was 5 mg OD. Patients were treated concurrently with Lu-177 DOTATOC therapy at intervals of 8 weeks (+/-1 week) with average of 4 sessions. Sample size calculation was based on the expected response of the combination to be 30% with power of 80 and type 1 of .05, compared to the known response rate of everolimus alone of 5%. Primary end point is safety. Other end points include response rate, PFS and OS. Results: Eleven patients, with progressive disease, were enrolled. Characteristics are summarized in the table. Everolimus MTD was 10 mg once daily. However, dose was reduced to 5 mg OD in 3 patients and to 5 mg once every other day in 2 patients. Median number of sessions of Lu-177: 3 sessions, and median cumulative dose: 300 mci. Most common G1-2 toxicities: stomatitis (90.9%), Nausea (72.7%), Fatigue (63.6%), anorexia (36.4%), diarrhea (36.4%) and skin and nail changes (36.4%). G3 toxicities (36%) were infection, fatigue, pneumonitis and neutropenia. No grade 4 toxicities. Reasons of discontinuation were toxicity in 3 patients, progression in 3, stroke in 1 and due to interruption of therapy in 4 patients. ORR: 1 PD, 1 PR and 9 SD. At median FU of 18.9 months, 7 patients are still alive, 3 died, and 1 lost to FU. Median PFS: 23.3 months. Conclusions: Combination of Everolimus and the Lu-177 PRRT appear to be safe and effective. Four patients, due to strict compliance criteria in the study protocol, were removed from the study prematurely resulting in undertreatment. Larger and randomized studies are required to confirm such findings.[Table: see text]
Understanding practices and gaps in multidisciplinary hepatocellular carcinoma (HCC) care within the community oncology setting.
Authors: Lucas Lorna , Philip Philip Agop , Gandee Marianne , Kramar Amanda 
Published: January 2019

390 Background: HCC incidence continues to rise and presents a myriad of complex challenges involving multi disciplines to screen, diagnose, and provide personalized therapy. Recent advances in diagnostics and therapies necessitate a well-coordinated multidisciplinary approach in managing HCC patients, signaling a need to understand care within community care. The study aimed to understand how multidisciplinary cancer programs were structured to manage HCC care and to identify challenges and practices for management of HCC, a cancer less commonly seen in community care settings. Methods: The Association of Community Cancer Centers (ACCC) developed a survey to identify factors associated with delivery and coordination of care for HCC patients. The survey deployed electronically in July 2018 to multidisciplinary providers, representing 17 oncology professions. Of responses (n = 31), 69% identified their care setting as a “non-teaching community hospital, freestanding cancer center, private practice or other.” Results: 61% of respondents indicated their cancer programs do not have specialized hepatobiliary multidisciplinary team. Among those who have hepatobiliary multidisciplinary teams the composition and degree of specialization varied. 85% of respondents that do not have a specialized hepatobiliary team indicated that HCC patients are managed in consultation with a general tumor board. 52% indicated their program discussed participation in clinical trials with all HCC patients, and 55% of cancer programs conducted HCC clinical trials. 52% indicated their program had a formal pathway that outlines adherence to the NCCN guidelines for HCC management, 5% were in the process of developing and 43% were not in the process of developing such a pathway. Of respondents that reported barriers their program faces (n = 13) 31% indicated lack of psychosocial services, lack of screening and no/limited access to clinical trials. 23% responded delayed treatment and 15% responded delayed diagnosis as challenges. Conclusions: Review of multidisciplinary care delivery for HCC patients revealed unique protocols and challenges within primarily community-based settings.
Dose intensity of neoadjuvant FOLFIRINOX (FFX) in borderline and locally advanced pancreatic cancer (LAPC): A comparison to the adjuvant benchmark.
Authors: Murphy Janet E. , Ly Leilana , Wo Jennifer Yon-Li , Ryan David P. , Clark Jeffrey W. , Yeap Beow Y , Drapek Lorraine C. , Blaszkowsky Lawrence Scott , Parikh Aparna Raj , Nipp Ryan David , Kwak Eunice Lee , Allen Jill N. , Corcoran Ryan Bruce , Faris Jason Edward , Zhu Andrew X. , Goyal Lipika , DeLaney Thomas F. , Ferrone Cristina , Fernandez-del Castillo Carlos , Weekes Colin D. 
Published: January 2019

392 Background: Optimal timing and duration of FFX for resectable, borderline resectable, and LAPC has not been established. The PRODIGE 24/CCTG PA.6 study used 12 cycles of adjuvant modified FFX (eliminating bolus 5FU, irinotecan at 150mg/m2) demonstrating superior DFS (21.6 mo) over gemcitabine (12.8 mo). However, only 48% of patients (pts) received 70% of intended chemo dosing, and 66.4% of pts completed all doses due to postoperative tolerability. We conducted total neoadjuvant therapy (TNT) studies in borderline and LAPC. (LAPC study included Losartan experimentally.) Dose intensity of TNT with FFX is compared to the benchmark adjuvant data. Methods: In this retrospective analysis, chemotherapy data were analyzed from NCT01821729 (LAPC) and NCT01591733 (Borderline). Both studies included 8 cycles of neoadjuvant FFX: b5FU 400mg/m2, CI 5U 1200mg/m2/d x 2d, oxaliplatin 85mg/m2, and irinotecan 180mg/m2. Results: 92 pts were studied: Borderline n = 43, LAPC n = 49. Sixteen of 92 (17.3%) patients discontinued chemotherapy prior to 8 cycles due to: withdrawal of consent (2), chemotherapy toxicity (6), progression (4), and disease-related complications (4). 82.6% of patients completed 8 doses. 61.4% of all bFU was given at the intended dose of 400 mg/m2. The mean relative dose intensity of b5FU (the actual cumulative dose relative to the planned cumulative dose over 8 cycles) was 72%. 65.5% of patients required a reduction in b5FU over eight cycles. Data for all chemotherapy are presented in Table 1. Overall, 71 of 92 patients (77.2%) had > 70% dose of FFX, with mean relative dose intensity of 81.2%. Among surgically resected patients, mPFS was 21.3 months in LAPC (n = 34) and 48.6 months in Borderline (n = 33). Conclusions: Compared to adjuvant therapy, dose intensity was achieved in a higher proportion of participants with TNT, utilizing a FFX regimen that included b5FU and irinotecan at 180mg/m2. PFS among resected patients reflects this highly active treatment. [Table: see text]
Clinicopathological features and outcomes of fibrolamellar hepatocellular carcinoma.
Authors: Chakrabarti Sakti , Kommalapati Anuhya , Tella Sri Harsha , Huffman Brandon M. , Yadav Siddhartha , Riaz Irbaz Bin , Goyal Gaurav , Borad Mitesh J. , Mahipal Amit 
Published: January 2019

393 Background: Clinicopathological features and the outcomes of patients with fibrolamellar hepatocellular carcinoma (FLHCC) are not clearly defined. Methods: Data were collected by retrospective chart review on 42 patients with FLHCC treated between 1990 and 2017 at the Mayo Clinic. Clinicopathological characteristics, response to treatment, recurrence pattern and survival were analyzed. Results: Of 42 patients (17 males and 25 females; median age at diagnosis 22 years, range 15 to 39), 10 patients (23%) had stage I disease and 32 patients (77%) had stage II to IVB disease. All 10 patients with stage I disease and 21 of 32 patients with stage II-IVB disease underwent resection at presentation. In stage I patient group, 6 patients experienced recurrence with a median time to recurrence of 30.5 months, resulting in a 5 year overall survival (OS) of 86%. Patients with stage II to IVB disease who underwent resection (n=21) at presentation had a median OS of 32.5 months and 5 year OS of 44%. In the upfront surgery group, 71% of the patients experienced recurrent disease. The median OS of patients with unresectable disease (n=11) was 10 months. Systemic therapy was given to 17 patients which included sorafenib, FOLFOX (5-fluorouracil/leucovorin and oxaliplatin), gemcitabine plus oxaliplatin, single agent adriamycin or gemcitabine, capecitabine plus interferon alfa, gemcitabine plus cisplatin, cisplatin plus adriamycin and nivolumab . Sorafenib was given to 9 patients and 4 patients achieved stable disease (SD) with duration ranging from 5 months to 5 years. One programmed cell death receptor positive-1 patient had a durable complete response after 2 months of therapy with nivolumab. Conclusions: In FLHCC, surgical resection was associated with prolonged OS. However, recurrences were common after the surgery. Limited benefit was derived from the systemic treatment. In rare cases, therapy with a checkpoint inhibitor may provide a viable treatment option.
A network meta-analysis of adjuvant systemic therapy in resected pancreatic cancer.
Authors: Chaves Porras Jorge , Perry Kaitlyn , Putri Rahmadian Amanda , Delos Santos Seanthel , Ko Yoo-Joung , Berry Scott R. , Doherty Mark , Chan Kelvin K. 
Published: January 2019

396 Background: Multiple randomized controlled trials (RCTs) have established several systemic therapy regimens as adjuvant therapy treatment options for resected pancreatic cancer, including modified FOLFRINOX (mFFX), gemcitabine and capecitabine (GemCap) and S1, mostly based on comparison with gemcitabine (Gem) alone. Many of these regimens have not been directly compared in RCTs and their relative survival benefits are unknown. Methods: A systematic review was conducted using MEDLINE, EMBASE, Cochrane Central and ASCO abstracts to identify phase III RCTs up to June 2018 that examined adjuvant systemic therapy in resected pancreatic cancer. Two reviewers independently reviewed the studies and discrepancies were resolved either by discussion or by a third reviewer. Data including study characteristics and outcomes including overall survival (OS) and disease-free survival (DFS) were extracted. Indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analyses (NMA) (R package “netmeta”) which maintains randomization within trials. Results: Nine phase III RCTs involving 3,394 patients and 6 regimens (5-flourouracil and folinic acid, Gem, gemcitabine and erlotinib (GemErl), GemCap, mFFX and S1) were identified. Hazard ratios (HR) and 95% confidence intervals (CI) of OS and DFS of selected comparisons from the results of the NMA are shown in the table. Conclusions: Both mFFX and S1 appeared to be superior to GemCap and can be considered as reasonable standard treatment options for suitable patients and as control arm regimens of future adjuvant clinical trials. [Table: see text]
Predictors of survival in pancreatic squamous cell carcinoma (PSCC): An analysis from the National Cancer Database (NCDB).
Authors: Kommalapati Anuhya , Tella Sri Harsha , Goyal Gaurav , Mahipal Amit 
Published: January 2019

399 Background: PSCC is a rare form of exocrine pancreatic malignancy with a dismal prognosis. Using the NCDB, we determined the prognostic factors and survival outcomes of PSCC in the United States. Methods: We performed a retrospective analysis of patients with histologically confirmed PSCC from 2004-2015 using NCDB. Kaplan-Meier method and log-rank test were used to perform overall survival (OS) analysis. Hazard Ratios were calculated using the Cox-proportional hazard method. Results: Of the 654 cases included in our analysis, 46% were female. Median age at diagnosis was 70 years and did not differ by sex (p = 0.19). The proportion of patients with stage I, II, III and IV diseases were 5%, 18%, 12%, and 54%, respectively (10%, unknown stage). Among these, 23% (35 of 150) of stage I and II disease, 10% (8 of 78) of stage III, and 2% (7 of 353) received surgical resection of the primary tumor. The rate of R0 resection was 74% in stage I and II; 38% in stage III; 29% in stage IV disease. Median OS for the entire cohort was 4 months and was significantly higher in patients who received surgical resection of the primary tumor (17 vs. 4 months, p < 0.001). On stage wise sub-group analysis, stage I-II patients had OS benefit from surgery (21 vs. 5 months, p < 0.001) as opposed to stage III (7 vs. 6 months, p = 0.31) and IV disease (5 vs. 3 months, p = 0.17). Adjuvant chemotherapy had no role in prolonging survival in stage I-II disease (20 vs 24 months, p = 0.6). Stage IV patients treated with chemotherapy had a better median OS than those without (5 vs. 2 months, p < 0.0001). On Cox multivariable analysis, stage IV disease (HR: 1.92 CI: 1.46-2.52, p < 0.001) and advanced patient age (HR: 1.02; CI:1.01-1.03, p < 0.001 were associated with poor OS, whereas OS was not dependent on the sex, race, grade, insurance status, surgery, and chemotherapy. Conclusions: This is the largest registry-based study on PSCC to date. PSCC had a diverse OS varied significantly according to increasing age and stage of the disease at presentation. Surgical resection of primary tumor was associated with improved OS in stages I-II, whereas chemotherapy improved OS in stage IV disease. The results of our study may aid the prognostication of patients and in treatment decision making.
A phase III, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of andecaliximab combined with mFOLFOX6 as first-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma (GAMMA-1).
Authors: Shah Manish A. , Yanez Ruiz Eduardo Patricio , Bodoky Gyorgy , Starodub Alexander , Cunningham David , Yip Desmond , Wainberg Zev A. , Bendell Johanna C. , Thai Dung , Bhargava Pankaj , Ajani Jaffer A. 
Published: January 2019

4 Background: Andecaliximab (ADX) is a monoclonal antibody that inhibits matrix metalloproteinase 9, an extracellular enzyme involved in matrix remodeling, tumor growth, and metastasis. A phase I/Ib study of mFOLFOX6 + ADX revealed encouraging antitumor activity in patients (pts) with gastric or gastroesophageal junction (GEJ) adenocarcinoma (median first-line, progression-free survival [PFS] of 9.9 months). Methods: This phase 3, randomized, double-blind, multicenter study investigated the efficacy and safety of mFOLFOX6 with/without ADX in pts with untreated HER2-negative gastric or GEJ adenocarcinoma. Randomization was 1:1 to mFOLFOX6 + ADX or mFOLFOX6 + placebo (PBO). Oxaliplatin was administered on Days 1 and 15 of each 28-day treatment cycle (total of 6 cycles), followed by leucovorin and 5-fluorouracil dosing on Days 1 and 15 of each 28-day treatment cycle until disease progression. ADX/PBO 800 mg was infused on Days 1 and 15 of each 28-day cycle until disease progression. The study had 85% power (one-sided significance of 0.025) to detect a hazard ratio of 0.7 for overall survival (OS) by intention-to-treat analysis using the log-rank test. Secondary endpoints were PFS, objective response rate (ORR, RECIST 1.1), and safety. Results: Between September 2015 and May 2017, 432 pts were randomized; 218 pts to ADX and 214 pts to PBO. Median (95% CI) OS was 12.5 (11.2, 14.0) vs 11.8 (10.3, 13.5) months in the ADX and PBO groups, respectively (HR 0.93 [0.74, 1.18], two-sided p=0.56). Median PFS was 7.5 vs 7.1 months in the ADX and PBO groups, respectively (HR 0.84 [0.672, 1.038], two-sided p=0.10). Median investigator assessed ORR was 50.5% vs 41.1% in the ADX and PBO groups, respectively (two-sided p=0.049). The most common treatment-emergent adverse events were nausea, diarrhea, neutropenia, and fatigue. There were no meaningful differences in the safety profile of the ADX vs PBO groups. Subgroup analysis is ongoing. Conclusion: Additionof ADX to mFOLFOX6 does not improve OS in pts with untreated HER2-negative gastric or GEJ adenocarcinoma. Clinical trial information: NCT02545504.
Oral chemotherapy as second-line treatment option for gemcitabine-refractory advanced pancreatic cancer with poor performance status.
Authors: Park Se Jun , Lee Myung Ah 
Published: January 2019

405 Background: There is few data for effective second-line treatment in advanced pancreatic cancer, and most patients have poor performance status after progressive disease. We evaluated the efficacy, toxicity, and median dose intensity of oral chemotherapy, capecitabine, or TS-1 in gemcitabine-refractory advanced pancreatic cancer for second-line treatment. Methods: Patients who have progressive disease after first-line gemcitabine-based chemotherapy were retrospectively analyzed between Jan. 2011 and Nov. 2017. These patients were treated with capecitabine or TS-1 as second-line treatment. Capecitabine were administered as 2,500 mg/m2 divided dose on day 1-14, followed by one week rest. In TS-1 group, TS-1 was taken orally based on patient’s BSA (60mg twice daily in BSA > 1.5, 50mg twice daily in BSA 1.25-1.5, and 40mg twice daily in BSA < 1.25) through 28 days, by two week rest. Median dose intensity was compared by calculating a percent of target dose achieved in the average cycle for each patient. Results: Of the total 62 patients, 41 patients were treated with capecitabine and 21 patients were treated with TS-1. The median age was 61 years for the capecitabine group compared with 62 years for the TS-1 group. In capecitabine group, males were 56%, and in TS-1 group, males were 66%. 29% of capecitabine group received prior fluorouracil base therapy, and 47% of TS-1 group were receiving such therapy. The objective response rate was similar in the two groups: 12.2% with capecitabine and 4.8% with TS-1 (p = 0.358). There was no difference in median progression free survival between capecitabine and TS-1 (2.1 months vs. 2.7 months, p = 0.102), however, TS-1 group showed better median overall survival time than capecitabine group (6.9 months vs. 4.6 months, p = 0.048). Most of the adverse events were similar in both group, except that grade 3 or 4 mucositis was more common in TS-1 group. There was no significant difference in median dose intensity between two groups. (Capecitabine 91.5% vs. TS-1 90.1%, p = 0.216). Conclusions: Oral agents such as TS-1 or capecitabine can be second-line treatment for advanced pancreatic cancer patients with poor performance status after progression to gemcitabine-based regimen.