bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-agent neoadjuvant chemotherapy improves response and survival in patients with resectable pancreatic cancer.
Authors: Maramara Taylor , Huston Jamie , Shridhar Ravi , Meredith Kenneth L 
Published: January 2019

409 Background: Neoadjuvant therapy (NT) for resectable pancreatic adenocarcinoma (PAC) continues to be debated. We sought to establish the impact of single agent (SAC) versus multi-agent chemotherapy (MAC) with or without radiation (RT) on survival in patients with resectable pancreatic cancer. Methods: Utilizing the National Cancer Database we identified patients with PAC who underwent up front surgery (UFS), SAC, or MAC ± RT followed by surgery. Patient characteristics and survival were compared with Mann-Whitney U, Pearson’s Chi-square, and the Kaplan-Meier method. Multivariable analysis (MVA) was developed to identify predictors of survival. All tests were two-sided and α < 0.05 was significant. Results: We identified 26,563 patients of which, 23,877 (89.9%) UFS, 1,482 (5.6%) NT+RT (SAC+RT 768, MAC+RT 560), and 1,204 (4.5%) chemo only (SAC 262, MAC 864) with a median age of 66 (25-90). The median tumor size was smaller, p = 0.003 and Charlson/Deyo was lower, p = 0.008 in the UFS. Despite this, the 90 day mortality was higher at 8% versus 7.5% in NT+RT and 4.8% in NT, p = 0.003. There were higher R0 resections in the NT+RT versus NT-RT or UFS, 82.4%, 80.5%, and 76%, p < 0.001. Additionally, there were less N1 disease in NT+RT 35.4%, 59.5%, and 68.1%, p < 0.001. Pathologic complete response (pCR) rates were higher in the NT+RT versus NT-RT, 3.1% versus 1.7%, p < 0.001. Examining the response rates by SAC±RT and MAC±RT, pCR was 0.5% in SAC, 2.8% SAC+RT, 2.2% MAC, and 3.3 MAC+RT, p = 0.004. The median survival was 22.2 mo in UFS, 23.1 mo in SAC, 26 mo in SAC+RT, 27.9 mo in MAC+RT, and 29.8 mo in MAC, p < 0.001. On multivariable analysis, age, Chalson/Deyo score, tumor size, grade, margin status, facility volume, and MAC were predictors of survival. Conclusions: Multi-agent chemotherapy with or without radiation improves overall survival, R0 resections rates, and complete pathological response rates in patients undergoing neoadjuvant therapy for resectable pancreatic cancer.
Neutrophil/lymphocyte ratio (NLR) may predict prognostic factor with gemcitabine, cisplatin (GC) for patients with advanced biliary tract cancer.
Authors: Otsuru Toru , Sakai Daisuke , Kimura Akie , Inagaki Chiaki , Nishida Naohiro , Iwagami Yoshifumi , Noda Takehiro , Asaoka Tadafumi , Gotoh Kunihito , Kobayashi Shogo , Eguchi Hidetoshi , Satoh Taroh 
Published: January 2019

410 Background: There is little information available about prognostic markers of GC (gemcitabine, cisplatin) in patients with advanced biliary tract cancer (BTC). Neutrophil/lymphocyte ratio (NLR) in several cancers was might to be a prognostic factor associated with clinical outcomes, we examine NLR in patient with BTC underwent chemotherapy (GC). Methods: Retrospective chart review for consecutive patients who underwent GC for advanced BTC in our institute were performed. The patients who were enrolled in ongoing clinical trials were excluded. Gemcitabine and cisplatin were administered intravenously at doses of 1,000 or 25 mg/m2, on day one and eight, every three weeks. We divided these patients based on estimated NLR, and evaluated the clinicopathological factors and survival in the two groups (NLR ≥ 3 or < 3). Results: 57 patients from 2013 to 2017 were reviewed. 23 patients were in NLR ≥ 3 group and 34 patients were in NLR < 3 group. Patients characteristics were as follows; median age, 68 years old (range: 38-83) years: male 36 (63%); primary tumor lesion, intrahepatic bile duct 6 (10%)/extrahepatic bile duct 32 (56%)/gallbladder 18 (32%)/ampulla of vater 1 (2%); therapeutic purpose, palliative 50 (88%)/adjuvant 5 (8%)/neoadjuvant 2 (4%); PS, 0/1. Response rate of the patients who had measurable lesion according to RECIST v1.1 was 17% (8/46), and disease control rate was 70% (32/46). The progression-free survival rate between the two groups is not significantly different. Although, the median overall survival (OS) of NLR ≥ 3 group was 11.8 months, while OS of NLR < 3 group was 29.2 months. The overall survival rate in the NLR ≥ 3 group was significantly lower than that in the NLR < 3 group ( P = 0.0339). Conclusions: Our study confirmed that high NLR is associated with worse OS and PFS, and suggested it may be a predictive marker for GC chemotherapy in patients with BTC.
Pulsed high-dose erlotinib with gemcitabine as second-line therapy for pancreatic adenocarcinoma.
Authors: Larson Christopher , Reid Tony R. 
Published: January 2019

421 Background: The options for treatment of pancreatic cancer follow progression on first line therapy are limited and associated with significant toxicity. Erlotinib has been approved for treatment of pancreatic cancer in first-line therapy. We conducted a phase I dose-escalation trial of erlotinib in combination with gemcitabine for patients that had failed first-line therapy. Erlotinib was administered by a novel pulse-dose schedule where the drug was given orally for 3 days every two weeks. Purpose: Assess the safety and determine a recommended phase II dose for pulsed high dose erlotinib in combination with gemcitabine for pancreatic cancer, and obtain preliminary data on activity. Methods: Patients with pancreatic cancer that progressed on or after first-line therapy were treated in a dose escalation study with erlotinib at 750 to 2,000 mg daily for three days every two weeks in combination with weekly gemcitabine at 1,000 mg/m2 for three weeks on and one week off. Results: No dose limiting toxicities were encountered and erlotinib-induced rash was mild and transient. Median overall survival was 6.7 months and 12-month overall survival was 27%. Progression free survival but not overall survival was longer in patients who did not previously receive gemcitabine. Rash was not associated with longer survival. Conclusions: The recommended phase II dose is erlotinib 2,000 mg daily for three consecutive days every two weeks in combination with gemcitabine. Tolerability was excellent, and outcomes were better than expected for second-line therapy in pancreatic cancer. Further studies are warranted, both as therapy after first-line and as first-line therapy for patients unable to tolerate more aggressive regimens. Clinical trial information: NCT02154737.
Real world eligibility for cabozantinib (C), regorafenib (Reg), and ramucirumab (Ram) in hepatocellular carcinoma (HCC) patients after sorafenib (S).
Authors: Fung Andrea S. , Tam Vincent C. , Meyers Daniel E. , Sim Hao-Wen , Knox Jennifer J. , Zaborska Valeriya O. , Davies Janine Marie , Ko Yoo-Joung , Batuyong Eugene , Cheung Winson Y. , Samawi Haider , Lee-Ying Richard M. 
Published: January 2019

422 Background: The CELESTIAL, RESORCE, and REACH-2 trials showed survival benefit of C, Reg, and Ram, respectively, when given after S to HCC patients. However, strict eligibility criteria (SEC) may limit generalizability. In clinical practice, modified eligibility criteria (MEC) may be used to offer treatments to select patients with slightly worse performance status (ECOG 2) or limited liver dysfunction (Child-Pugh (CP) B7). This study evaluated which patients in the real world would be eligible for these new treatments using SEC and MEC, and their prognostic impact. Methods: HCC patients who received S between 01/2008-06/2017 in British Columbia, Alberta, Princess Margaret Cancer Centre, and Sunnybrook Cancer Centre in Canada were included. Clinical, pathologic, laboratory and outcome data were collected. Patients were classified as eligible or ineligible based on available CELESTIAL, RESORCE, REACH-2 clinical trial SEC or MEC. Median overall survival (mOS) for these groups was assessed using the Kaplan-Meier method. Results: A total of 730 patients were identified. Using SEC, only 13.1% of patients would be eligible for C, Reg, or Ram (table). Expanding eligibility to include patients who meet MEC increased the proportion of eligible patients to 31.7%. Patients who met SEC had longer mOS compared to those who were ineligible. The most common reasons for not meeting SEC across all 3 trials were ECOG ≥ 2 (61.7%) and CP ≥ B (63.9%). Higher ineligibility for Reg or Ram was likely driven by strict trial-specific criteria, with 28.0% of patients ineligible for Reg due to S intolerance and 58.9% ineligible for Ram due to AFP < 400. Conclusions: Only a small proportion of real-world HCC patients would be eligible for C, Reg, or Ram based on SEC. More than twice as many patients would likely receive treatment if MEC were applied. If MEC are adopted, ongoing real-world evidence generation will be important to evaluate outcomes in these unstudied patient groups. [Table: see text]
Regional, racial/ethnic, and socioeconomic disparities and treatment outcomes in patients with hepatocellular carcinoma (HCC) in the United States.
Authors: Parikh Neehar , Malahias Laura , Brown Robert S , Cabrera Roniel , Jones Patricia Denise , Landis Charles , Lee Hannah , Mantry Parvez , Mena Edward , Poddar Nishant , Reddy K. Rajender , Shrestha Roshan , Thuluvath Paul , Zink Richard , Singal Amit G. 
Published: January 2019

424 Background: Racial/ethnic (R/E) minorities and patients of low socioeconomic (SE) status are reported to have higher mortality related to HCC than their counterparts. However, prior studies are limited to administrative datasets without annotation for clinical covariates or represent single-center data with limited generalizability. The aim of this analysis was to characterize geographic, R/E, and SE disparities in HCC presentation, treatment, and survival among a representative sample of HCC patients in the US. Methods: TARGET-HCC is an observational, retrospective/prospective study of patients with HCC from academic and community sites. Complete medical records from consented patients are abstracted into a secure database. Multivariable logistic regression with random intercepts for site and Cox proportional hazard models with frailty adjustment were fit with adjustment for age, sex, BMI, liver disease etiology (LDE) and history of alcohol abuse to identify factors associated with early HCC detection, receipt of curative-intent therapy (CIT) and overall survival. Results: 925 patients with HCC (63% non-Hispanic white, 21% black, and 8% Hispanic) were consented from 42 sites in the US (22% Northeast, 27% Southeast, 21% Midwest, 14% South, and 16% West). Median age was 64 years and 76% were men. The most common LDE was hepatitis C (72%), and 72% had Child Pugh A cirrhosis. Most patients were diagnosed with early-stage HCC (72% Barcelona Clinic Liver Cancer 0/A). CIT was the initial therapy in 249 (32%), including 32% of BCLC 0/A. Although early tumor detection and CIT did not differ by region or R/E, there were SE disparities in CIT. Among those with early stage HCC, patients with private insurance [OR = 0.51, 95% CI (0.29, 0.91)] or Medicaid [OR = 0.50, 95% CI (0.25, 0.97)] were significantly less likely to undergo CIT. Overall survival was associated with BCLC stage and type of HCC treatment, with no significant association with region, R/E, or insurance. Conclusions: In this sample of HCC patients, there were no geographic or R/E disparities in early detection, treatment, and survival although SE disparities in administration of CIT were identified and warrant further study.
Lymphocyte-to-monocyte ratio and neutrophil-to-lymphocyte ratio independently predict survival in resected small bowel adenocarcinoma.
Authors: Huffman Brandon M. , Patel Shruti , Yadav Siddhartha , Jin Zhaohui , Mahipal Amit 
Published: January 2019

426 Background: Small bowel adenocarcinoma is a rare malignancy affecting approximately 2,000 patients per year. There is a paucity of evidence prognosticating patients with small bowel adenocarcinoma. We aimed to evaluate multiple factors in patients with resected small bowel adenocarcinoma to determine any association with survival outcomes. Methods: Ninety three patients who underwent resection for stage I-III small bowel adenocarcinoma were retrospectively identified utilizing the pathology database at a single tertiary referral institution. All patients had complete follow up data and were included in the survival analysis. JMP software was used for statistical analysis. Overall survival was performed utilizing Kaplan-Meier method, and log-rank tests were used for statistical comparisons. Cox proportional hazards were performed to control for age, gender, location of tumor, tumor size, tumor stage, and adjuvant therapy. Sensitivity analysis was performed to establish best cutoff points for continuous variables. All tests were two sided and a P value of < 0.05 was considered significant. Results: The median age at diagnosis was 65 years (range 32-90). 61% were male. Median tumor size was 4.5 cm. There were 20, 36, and 37 patients with stage I, stage II, and stage III disease, respectively. Median overall survival (OS) was 151 months, 104 months, and 44 months for stages I, II, and III disease. In a multivariate analysis, independent predictor factors included presurgical lymphocyte to monocyte ratio (LMR) > 4.0, with a Hazard Ratio (HR) 0.13 (95% CI 0.007-0.69, p = 0.01), presurgical neutrophil to lymphocyte ratio (NLR) < 8.0, HR 0.39 (95% CI 0.17-0.96, p = 0.04), and tumor size < 7.5 cm, HR 0.22 (95% CI 0.07-0.85, p = 0.03). Stage, age, T stage, and N stage influenced overall survival in univariate analysis, but were not statistically significant on multivariate analysis. Conclusions: LMR and NLR independently predict survival in patients with resected small bowel adenocarcinoma.
Phase I study of tramatinib combined with sorafenib in patients (pts) with advanced hepatocellular cancer (HCC).
Authors: Wang Emilie , Kim Dae Won , Mahipal Amit , Chen Dung-Tsa , Cao Biwei , Masawi Fadzai , Kim Richard D. 
Published: January 2019

431 Background: RAS/RAF/MEK/ERK (MAPK) signaling pathway is associated with proliferation, progression, and survival of HCC. Preclinical data suggests that activation of MAPK pathway may be one of resistant mechanisms of sorafenib, and the combination of MEK inhibitor and sorafenib can induce synergistic anticancer activity in HCC. We evaluated the safety and efficacy of trametinib (MEK inhibitor) combined with sorafenib in HCC. Methods: This was a phase I single center study with standard 3+3 design for pts with treatment naïve advanced HCC. The primary endpoints are determining dose limiting toxicities (DLT) and maximum tolerated dose (MTD). Secondary endpoints include overall survival (OS), progression free survival (PFS), and disease control rate (DCR). Initial plan was to enroll pts in 4 escalating dose levels (dl)—trametinib 1mg daily (qd)/sorafenib 200mg twice daily (bid)(dl 1), trametinib 1.5mg qd/sorafenib 200mg bid (dl 2), trametinib 1.5mg qd/sorafenib 400mg bid (dl 3), trametinib 2mg qd/sorafenib 400mg bid (dl 4). Eligible pts had advanced unresectable HCC, ECOG PS 1, Child-Pugh Score 6, and adequate organ function. Results: 17 pts were treated in 3 different dl of trametinib and sorafenib (3 in dl 1, 8 in dl 2, and 6 in dl 3). Median age was 65 years (range 40-80) with 64.7% male. All pts were evaluated for toxicity, but only 15 were evaluable for DLT. 2 pts were replaced as they came off of study within 1 month (1 pt in dl 3 due to varices unrelated to the study drug, 1 pt in dl 2 for voluntary withdrawal due to side effects). DLT was noted in dl 3 with 2 pts (grade 4 hypertension (HTN) and grade 3 elevated (elev) of bilirubin/AST/ALT > 7 days). Most common grade 3/4 treatment related adverse events were elev AST (47.1%), HTN (23.5%), elev Alk Phos (17.6%), elev ALT (5.9%), elev bilirubin (5.9%), and diarrhea (5.9%). The median PFS was 4.0 months (mo), and median OS was 5.8 mo. 11 pts were evaluable for response after cycle 2 (8 stable disease (SD), 2 disease progression (PD), 1 partial response). 3 pts were evaluable for response after cycle 4 (1 SD, 2 PD). DCR was 63.6%. Conclusions: Trametinib and sorafenib can be safely administered up to trametinib 1.5mg qd and sorafenib 200mg bid for pts with advanced HCC. Clinical trial information: NCT02292173.
Outcomes for patients with borderline resectable (BR) and locally advanced (LA) pancreatic cancer (PC) treated with induction FOLFIRINOX (FFX) +/- radiation (RT) followed by surgery compared to induction FFX followed by consolidative RT.
Authors: Cecchini Michael , Miccio Joseph , Pahade Jay , Lacy Jill , Salem Ronald R , Johnson Skyler Bryce , Stein Stacey , Kortmansky Jeremy S. , Johung Kimberly 
Published: January 2019

437 Background: Induction FFX for PC deemed either BR or LA at diagnosis provides an opportunity to downstage pts with the aim of an R0 surgery. The addition of RT after induction FFX may further downstage. However, there is a paucity of data regarding long-term survival for BR and LA patients successfully downstaged and resected. We performed a retrospective review of BR and LA PC treated with induction FFX +/- RT followed by surgery or consolidative RT at the Yale Cancer Center (YCC) to assess survival in these two cohorts. Methods: Clinical data was abstracted for pts with BR or LA PC who had surgery or received consolidative RT without surgery after induction FFX +/- RT at the YCC from 2010-2018. Surgical pts were re-reviewed by a radiologist to assess vascular involvement (BR vs. LA) using NCCN criteria. PFS and OS for surgery and consolidative RT were analyzed by the Kaplan-Meier method. Survival was compared via the log rank test. Results: 102 pts met inclusion criteria (BR=47, LA=55), 41 pts had surgery [BR=29/47 (62%) LA=12/55 (22%)] and 61 pts had consolidative RT [(BR= 18/47 (38%), LA= 43/55 (78%)] after induction FFX. 18 surgery pts received RT prior to resection and all surgery pts had R0 resection. Median follow up was 25 mo (range 5 – 97). Median PFS with surgery was 22 mo (95% CI 15 – 59) vs 14 mo (95% CI 10.9 – 20.1) with consolidative RT (p<0.001), while OS with surgery was 42 mo (95% CI 25-NR) vs 20 mo (95% CI 17-25) without surgery (p<0.001). For pts with ≥ 2 yr follow up, 12/22 (55%) surgery pts and 17/18 (94%) consolidative RT pts relapsed. For pts with ≥ 3 yr follow up, 6/12 (50%) surgery pts and 10/10 (100%) consolidative RT pts relapsed. 2 yr PFS and OS was 45% (95% CI 28-61) and 74% (95% CI 57 – 86) with surgery versus 15% (95% CI 7-27) and 40% (95% CI 26-53) with consolidative RT. Conclusions: Surgery was associated with a high R0 rate and prolonged PFS and OS compared to consolidative RT in pts with BR and LA PC after FFX +/- RT. However, survival benefit was not statistically significant when selecting only LA pts although numbers are limited.
Resection of primary tumor in liver only metastatic midgut neuroendocrine tumors.
Authors: Manguso Nicholas , Lee Jaewon , Hendifar Andrew Eugene , Tuli Richard , Gangi Alexandra 
Published: January 2019

446 Background: Surgical management of metastatic midgut neuroendocrine tumors (NET) remains controversial. Resection of primary tumor only without liver resection is advocated only in select patients, frequently for palliation. Additionally, no standard algorithm exists, and the risk profile for these patients is not well documented in the literature. We evaluated these midgut NETs with liver metastasis in the National Cancer Data Base (NCDB) to determine if resection of the primary tumor only affected survival outcomes. Methods: The NCDB was queried to identify patients with liver only metastatic midgut NET tumors between 2010 and 2015. Patients who underwent surgery of their liver metastasis were excluded. The cohort was separated into two groups, those who underwent resection of the primary tumor and those who did not. Patient demographics, year of diagnosis, clinicopathologic tumor characteristics and Charlson/Deyo comorbidity index were compared among the two groups. The primary outcome was overall survival (OS). Kaplan-Meier estimates were used to predict OS. Results: One-thousand nine hundred fifty-two patients with median age of 63 were identified. Median tumor size was 2.4 cm. Of these, 1,295 (66.0%) patients underwent resection of the primary tumor and 667 (34.0%) did not. Patients undergoing resection were younger (median age 63 vs. 65, p < 0.001) and had smaller tumors (median 2.3 cm vs. 3.0 cm, p < 0.001). There was no difference between the groups with respect to sex, year of diagnosis or Charlson/Deyo Comorbidity Score. Median follow up time was 42.8 months (IQR 29.7). A total of 483 deaths occurred in the entire cohort with a 5-year OS of 60.8%. The 5-year OS for patients undergoing resection of the primary tumor was 65.9% and 49.3% for those not undergoing resection (p < 0.001). Conclusions: Patients with liver only metastatic midgut neuroendocrine tumors had an overall survival advantage when the primary tumor was resected. Patients with liver only metastatic midgut NET may benefit from surgical resection and should be evaluated for surgery at the time of diagnosis.
Local control following stereotactic body radiotherapy to adrenal oligometastases.
Authors: Figura Nicholas B , Oliver Daniel Eli , Johnstone Peter Anthony , Hoffe Sarah E. , Frakes Jessica 
Published: January 2019

447 Background: The role and associated risks of stereotactic body radiotherapy (SBRT) for adrenal metastases remain unclear. We report our single institution experience and report novel techniques to selectively dose-escalate treatment while concurrently minimizing dose to nearby critical structures. Methods: We retrospectively reviewed patients with evidence of metastatic adrenal disease originating from any primary histology treated with SBRT from 2013 to 2018. The primary endpoint was local control (LC). Secondary endpoints were disease-free survival (DFS), overall survival (OS), and treatment-related toxicity. LC, DFS, and OS were calculated with Kaplan-Meier analysis. Univariable and multivariable analysis were performed with long-rank and Cox proportional analysis. Results: A total of 45 adrenal metastases in 41 patients received SBRT. The median age was 67 years (range 40-80). The most common primary histologies were non-small cell lung cancer (51%), renal cell carcinoma (24%), and small cell lung cancer (10%). The median gross internal and planned target volumes were 21.23cc (range, 3.1–124.7cc) and 31.68cc (range, 5.2–175.9cc), respectively. The median dose administered was 50 Gy with 30 (67%) lesions receiving ≥50 Gy and 14 (31%) receiving 60 Gy. Twenty-six (58%) lesions were selectively dose-painted. Of the 42 simulations, 26 (62%) were treated supine, 5 (12%) prone, and 11 (26%) in the left lateral decubitus position. At a median follow-up of 10.5 months, there were 3 local recurrences (LR). 12-month LC rate was 96% with a median LC of 35 months. All three LR were in the metachronous, oligometastatic patients. One patient developed a hypertensive crisis which required intravenous antihypertensives. Conclusions: Adrenal SBRT for oligometastatic disease is a reasonable, noninvasive option with excellent LC and minimal toxicity. Lesions in close proximity to radiosensitive organs may benefit from techniques, such as dynamic patient positioning and selective dose-painting, for further dose-escalation to optimize LC rates while simultaneously limiting associated toxicity risks.