bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between sarcopenia and treatment outcomes in patients with pancreatic cancer undergoing chemoradiation.
Authors: Patel Kajal , Shaikh Talha , Wang Lora S , Hoffman John Parker , Cohen Steven J. , Meyer Joshua E. 
Published: February 2017

415 Background: Sarcopenia (Sp) or severe loss of muscle mass is a prognostic factor in cancer patients. We assessed the association between Sp and outcomes in borderline resectable or locally advanced/unresectable pancreatic cancer patients undergoing chemoradiation (CRT). Methods: We reviewed all patients who underwent CRT at an NCI-designated cancer center between 2007-2012. Patients with available pre-treatment imaging were included in the analysis. Sp was defined as a lumbar skeletal muscle area/height of < 55.4 cm2/m2 for males and < 38.9 cm2/m2for females. Sp was correlated to treatment toxicity, cause specific survival (CSS), and overall survival (OS). Analysis was performed using chi-square test for categorical variables and Mann-Whitney U test for continuous variables. Kaplan-Meier method and Cox regression was used for survival analysis. Results: A total of 86 patients met the inclusion criteria with 32 (37%) patients being sarcopenic. The median age was 70 (range 46-91) with a median follow-up of 14 months (3-68). The majority of patients were male (57%), had T3 disease (47%), or were borderline resectable (63%). Twenty nine (33.7%) patients underwent surgery. Sarcopenic patients were less likely to undergo surgery (p = 0.024) versus non-sarcopenic patients. Otherwise there was no difference in clinical or treatment factors. The 12-month actuarial OS for patients with and without Sp was 47.9% and 70.7%, respectively (p = 0.047). The 12-month actuarial CSS for patients with and without Sp was 48% and 76%, respectively (p = 0.007). On multivariable analysis, after controlling for T-stage, N-stage, resectability, gender, pre-treatment CA 19-9, and surgery, Sp was no longer associated with CSS (HR 0.284 95% CI 0.774-2.398) or OS (HR 1.077 95% CI 0.626-1.853). Surgery remained associated with CSS (HR 0.205 95% CI = 0.102-0.412) and OS (HR 0.187 95% CI 0.096-0.363). T-stage also remained associated with both CSS (HR 0.616 95% CI 0.410-0.925) and OS (HR 0.649 95% CI 0.440-0.957). Conclusions: The presence of Sp decreases the likelihood of undergoing curative surgery for pancreatic cancer. This may be another useful tool to identify poor prognosis patients.
Comparative effectiveness and resource utilization of nab-paclitaxel plus gemcitabine (nab-P+G) versus gemcitabine monotherapy (G) in first-line treatment of advanced pancreatic adenocarcinoma (PDAC) in a U.S. community oncology setting.
Authors: Braiteh Fadi S. , Patel Manish , Parisi Monika , Ni Quanhong , Park Si yeon , Faria Claudio 
Published: February 2017

429 Background: Based on a randomized clinical trial (RCT), nab-P+G had superior overall survival (OS) compared to G for the treatment of advanced PDAC, but limited data is available comparing the effectiveness of these treatment options in a real-world setting. The objective of this study is to compare treatment patterns of patients receiving nab-P+G versus G for first-line treatment of PDAC. Methods: A retrospective cohort study was performed using fully de-identified data from a nationally representative electronic medical record platform of 1,300 community oncology physicians. Patients diagnosed with advanced PDAC between September 2013 and October 2014 who received first-line therapy with either nab-P+G or Gm were included in the analysis. We calculated the median time to treatment discontinuation (TTD) and database persistence (DP), a proxy for OS, using the Kaplan Meier method, and assessed supportive care usage with Poisson regression. Results: Out of 851 patients, 168 met eligibility criteria for the analysis (nab-P+G, n=122; G, n=46). Patients in the nab-P+G arm were younger (mean age 67.0 v 72.0; p <0.01) and mostly males (60% v 44%). Other baseline characteristics were comparable. Patients treated with nab-P+G had a statistically significant longer median TTD (3.4 v 2.2 mos; p <0.01) and median DP (8.6 v 5.3 mos; p=0.03). Patients receiving nab-P+G had fewer AEs-related to discontinuation (18% v 26%); but they utilized more doses of granulocyte-colony stimulating factor (2.02 v 0.73 doses, p<0.01), erythropoietin-stimulating agents (0.90 v 0.54, p<0.01) and steroids (7.89 v 0.58 doses, p<0.01) per 100 days compared to patients receiving G. Conclusions: Similar to the RCT comparing nab-P+G with G,patients receiving nab-P+G experienced significantly longer TTD and DP in this real-world analysis compared to patients receiving G. Additionally, patients receiving nab-P+G had fewer AEs leading to discontinuation compared to patients receiving G. More supportive care may have been used in the nab-P+G group due to longer treatment duration.
Outcome analysis of primary liver carcinomas.
Authors: Doyle Maria Majella , Vachhajarani Neeta , Saad Nael , Fowler Kathryn , Tan Benjamin R. , Brunt Elizabeth , Chapman William C. 
Published: February 2017

438 Background: Treatments for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCCa) are established. Significant debate exists over optimal treatment for biphenotypic primary liver carcinomas (PLC) with combined HCC and IHCCa (B-PLC) and is considered to be a contraindication for transplantation. The purpose of this analysis is to determine single center outcomes of patients with B-PLC compared to HCC and IHCCa. Methods: A prospective database was reviewed to determine treatments and survivals of patients with HCC, IHCCa and B-PLC. Results: From 1/1/2009 to 12/31/2014, 810 patients with PLC were treated with resection (LRx) (n = 117), liver transplant (OLT) (n = 224) or liver directed therapy (LDT) (n = 469). 723 patients had HCC, 34 had IHCCa and 53 had B-PLC. Overall Survival (OS) in the LDT group, was similar comparing all tumor types at 1 yr (61.7%) and 3 yrs. (23.8%) (p =.3) Median survival (MS) was 16.2 months. OS in the LRx group was also similar between tumor types (1yr 81.1% and 5yrs. 41.1%, p =.2) and MS was 40.9 months. Comparing OLT patients with HCC (n = 212, 77% within Milan) to B-PLC (n = 10, 70% within Milan), OS (1yr 92.5% and 5 yrs. 77.0%, p =.8) was comparable and so also were disease-specific (1yr 99.0% and 5yr 97.3%, p =.6) and disease-free (1yr 88.7% and 5yrs. 73.5%, p =.4) survivals. OS for patients with B-PLC was significantly greater in patients receiving OLT vs. LRx or LDT (p =.005). Conclusions: Biphenotypic PLC has a poor prognosis and has been considered a contraindication for OLT. In this limited series, however, outcomes with transplantation appear acceptable.
A matched pair analysis of five-fraction stereotactic body radiation therapy versus protracted conventional radiation therapy in patients receiving chemotherapy for locally advanced pancreatic cancer.
Authors: Koroulakis Antony , Prins Petra , Gabrielson Andrew , Silveri Chris , Hwang Andrew , Abdulkadir Saman , McCullough Brianna , Marshall John , Pishvaian Michael J. , He Aiwu Ruth , Smaglo Brandon George , Collins Sean P. , Unger Keith Robert 
Published: February 2017

444 Background: Stereotactic body radiation therapy (SBRT) is a novel treatment modality for unresectable, locally advanced pancreatic cancer (LAPC). SBRT delivers high doses of radiation over a shorter duration, with minimal acute toxicities, compared with conventional radiation therapy (CRT) using intensity modulated radiation therapy (IMRT) or 3D conformal techniques (3D-CRT). Few studies have compared outcomes between SBRT and CRT techniques. We conducted a retrospective matched pair analysis of LAPC patients receiving chemotherapy and either SBRT or CRT to assess local control (LC), progression-free survival (PFS), and overall survival (OS). Methods: We retrospectively analyzed 28 patients with LAPC who were treated between August 2006 and August 2014 with 5-FU- or gemcitabine-based chemotherapy combined with CRT (45–56 Gy over 25–28 fractions) or SBRT (25–30 Gy over 5 fractions). Fourteen patients treated with CRT were matched with 14 patients treated with SBRT for age (< 65 vs. ≥ 65 years); nodal staging (N0 or N1); and chemotherapy type (gemcitabine-based or 5-FU-based, administered either concurrently or as induction therapy). Tumor response was assessed using RECIST and all outcomes were calculated from the date of diagnosis. The Log Rank test of Kaplan-Meier curves was used for statistical analyses. Results: Median follow-up time was 11 months (mo). The median duration of LC, PFS, and OS for the entire cohort was 11, 8, and 14 mo, respectively. Median duration of LC was 10 mo for CRT and 11 mo for SBRT (p > 0.05). Median PFS was 8 mo for both groups (p > 0.05). The median OS times were 12 mo for SBRT and 16 mo for 3D-CRT/IMRT (p > 0.05). Conclusions: In this small matched-pair analysis, LAPC patients treated with chemotherapy had similar outcomes following 5 fractions of SBRT as compared with a protracted course of CRT. Given the shorter treatment duration with SBRT, further study is warranted with increased cohort sizes and stratification by other patient and disease characteristics.
Are practice patterns of high-volume pancreatic surgeons distinct from low-volume pancreatic surgeons? A IHPBA/AHPBA web-based survey study.
Authors: Macedo Fransisco Igor , Anantha Sandeep , Race Alice J , Singh Awinderpreet , Jacobs Michael J , Parikh Janak A 
Published: February 2017

449 Background: Pancreatoduodenectomy (PD) is still one of the most complex operations with varied intraoperative techniques and postoperative management. The surgeon volume performing this complex surgery can determine patient outcomes and they might have distinct practice patterns. We aim to compare the practice patterns in perioperative management between high- (HV) and low-volume (LV) hepatobiliary surgeons. Methods: A 25-item survey questionnaire was electronically distributed using Survey Monkey to IHPBA and AHPBA members between May and August 2015 regarding their practice patterns for PD. HV surgeons were defined as those performing greater than 10 PD per year. Results: A total of 285 responses were included (HV, n=229; LV, n=57). The majority of participants were from United States (34.7%), Asia (14.3%) and Europe (28.1%). A significant higher proportion of LV surgeons were observed in Europe (p=0.04) and Asia (p=0.003). LV surgeons are more likely to continue perioperative antibiotics beyond 24 hours postoperatively (57.1% vs. 36.2%, p=0.009) and use more drains (p=0.04), however less likely to routinely measure postoperative drain amylase (73.6% vs. 85.6%, p=0.003). No significant difference was observed regarding management of infection, bile culture, or wound care. Conclusions: Practice patterns are variable between LV and HV pancreatic surgeons. LV surgeons are more likely to prolong prophylactic antibiotics, and use more suction drains, however HV surgeons have closer monitoring for signs of pancreatic leak. Further studies are warranted to elucidate the impact of these variations on surgical outcomes of patients undergoing pancreatoduodenectomy.
Carcinoid syndrome-related symptoms in pancreatic neuroendocrine tumors (pNETs) and impact on health care utilization.
Authors: Broder Michael S. , Chang Eunice , Reddy Sheila R. , Neary Maureen 
Published: February 2017

450 Background: PNETs, rare neoplasms originating from secretory neuroendocrine cells, produce peptides and neuroamines causing hormonal syndromes, including carcinoid syndrome (CS). Somatostatin analogues (SSAs) are usual 1st-line treatment; everolimus and sunitinib are targeted therapies (TT) approved for progressive disease. Carcinoid or hormonal symptoms associated with CS may occur in pNET and are treated with SSAs. Information is limited on impact of these symptoms on health resource use in pNET. Methods: This retrospective cohort study merged 2 large HIPAA-compliant claims databases and identified pNET patients (ICD-9-CM 157.4) initiating treatment with TT or cytotoxic chemo (CC) from 2009-2012. Patients had no prior TT or CC for pNET for 1 year preindex and were continuously enrolled 1 year postindex. Descriptive statistics were reported for comorbidities and health care use, overall and by presence of symptoms defined to include: diarrhea, nausea/vomiting, flushing, cardiac palpitations, asthma, wheezing, fatigue, hypotension, or dizziness. Chi-square and t-tests were used for analyses of categorical and continuous variables, respectively. Results: This study included 338 newly treated pNET patients with 1 year followup; 237 1st-line CC and 101 TT (64 everolimus, 37 sunitinib). Mean age was 54.5; 46% female. Patients had mean of 5 (SD 2.0) chronic conditions and Charlson Index of 10.1 (SD 2.9). Utilization included 43.5% hospitalizations, 48.8% ED visits, and mean of 25.5 (SD 24.8) office visits. 212 (62.7%) patients had symptoms. Other conditions were infection (34.9%) and anemia (29.9%). PNET patients with symptoms had considerably higher rates of hospitalization, ED visits, and office visits than those without: 57.5% vs. 19.8%, 64.2% vs. 23.0%, mean 29.2 vs. 19.3, all P < 0.001. Conclusions: In this study, nearly 2/3 of treated pNET patients had carcinoid or hormonal symptoms; about 1/3 had infection and anemia. Symptoms may influence drug treatment patterns. PNET patients with symptoms were high utilizers of health resources; over half were treated as inpatients and more sought ED care. This increased use may result from a high burden of symptoms and comorbid conditions.
Comprehensive genomic profiling of advanced colorectal carcinoma in the course of clinical care to identify KRAS insertions not detected by focused molecular testing.
Authors: Rankin Andrew , Schrock Alexa Betzig , Elvin Julia Andrea , Chmielecki Juliann , Erlich Rachel , Morosini Deborah , Frampton Garrett Michael , Grothey Axel , Rosenblum Alan , Bufill Jose A. , Helton Derek A. , Sequeria Judy , George Thomas J. , Klempner Samuel Jacob , Ross Jeffrey S. , Stephens Phil , Miller Vincent A. , Ali Siraj Mahamed 
Published: February 2017

497 Background: As activating RAS mutations have been shown to predict lack of benefit from anti-EGFR therapies in advanced CRC, NCCN guidelines recommend testing for KRAS exon 2 and non-exon 2 mutations; however, these alterations are thought to explain only a subset of de novo resistance to targeted therapy. In a large set of CRC assayed with comprehensive genomic profiling (CGP) in the course of clinical care, we assessed the frequency of less common KRAS short insertions that may predict failure of anti-EGFR therapy. Methods: 4,422 CRC cases were assayed with CGP performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of > 650X for at least 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. All classes of genomic alterations (GA) were identified, including base pair substitutions, insertions/deletions, copy number alterations, and rearrangements. Pertinent available prior molecular testing results and clinical history was reviewed for selected cases. Results: Out of 4,422 CRC cases analyzed, KRAS short variants were identified in 50.9% of cases. A majority of cases contained a KRAS alteration at either codon G12 (35.5%) or G13 (9.1%), while alterations at codons Q61 or A146 were identified in 2.2% and 3.1% of cases, respectively. KRAS insertions were identified in 8 ( < 0.5%) cases. All KRAS insertions identified fell within codons 9-13, and 6/8 cases harbored V9_G10 insertions. Out of 6 patients with prior KRAS testing results available, 5 (83%) were negative by previous testing. Conclusions: CGP identifies KRAS insertions within or adjacent to hotspot regions in CRC cases which have previously tested negative for KRAS mutations. Given the importance of KRAS alterations in predicting lack of response to anti-EGFR therapies in CRC, accurate detection of these alterations in the course of clinical care is essential for effective treatment. CGP offers the possibility of identifying KRAS insertions that may impact efficacy of anti-EGFR targeted therapy and should be considered when previous focused testing for KRAS mutations is negative.
A randomized, open-label, multicenter, adaptive phase 2/3 study of trastuzumab emtansine (T-DM1) versus a taxane (TAX) in patients (pts) with previously treated HER2-positive locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (LA/MGC/GEJC).
Authors: Kang Yoon-Koo , Shah Manish A. , Ohtsu Atsushi , Van Cutsem Eric , Ajani Jaffer A. , van der Horst Tina , Harle-Yge Marie-Laurence , Piao Yongzhe , Althaus Betsy , Thuss-Patience Peter C. 
Published: February 2017

5 Background: Trastuzumab (H) + capecitabine/fluorouracil + cisplatin is standard of care for 1st-line HER2-positive MGC/GEJC but there is no established HER2-targeted 2nd-line regimen. T-DM1 (H linked to DM1) is approved for HER2-positive metastatic breast cancer previously treated with H + TAX (separately or in combination). This and preclinical HER2-positive GC models provided the rationale for GATSBY (NCT01641939). Methods: GATSBY is a 3-arm randomized, adaptive, seamless phase 2/3 global study of T-DM1 vs TAX in pts with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization-positive), unresectable LA/MGC/GEJC who progressed during or after 1st-line fluoropyrimidine + platinum ± HER2-targeted therapy. Pts were initially randomized 2:2:1 to T-DM1 3.6 mg/kg every 3 weeks (q3w), T-DM1 2.4 mg/kg weekly (qw), or physician’s choice of paclitaxel 80 mg/m2 qw or docetaxel 75 mg/m2q3w. An independent data monitoring committee selected T-DM1 qw for further study and subsequent patients were randomized 2:1 to this or TAX. The primary endpoint is overall survival (OS); all T-DM1 qw data are analyzed, including dose selection. Results: At clinical cutoff, 06/30/15, 415 pts had been randomized overall: 228 to T-DM1 qw, 117 to TAX (70 T-DM1 q3w pts reported separately); 77.4% had prior HER2-targeted therapy; 29.9% prior gastrectomy; 46.1% were Asian. Efficacy/safety are tabulated. Conclusions: T-DM1 2.4 mg/kg qw did not show an efficacy benefit over TAX. Grade ≥3 AE rates were numerically lower with T-DM1 vs TAX and rates of SAEs, fatal AEs, and treatment discontinuations due to AEs were comparable between arms. Clinical trial information: NCT01641939. [Table: see text]
Outcomes by hypomagnesemia (hypomag) in the randomized phase III ASPECCT trial of patients (pts) with chemofractory wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC).
Authors: Peeters Marc , Kim Tae Won , Li Jin , Cascinu Stefano , Ruff Paul , Suresh Attili Venkatasatya , Thomas Anne , Tjulandin Sergei , Guan Xuesong , Hoang Tien , Hei Yong Jiang , Price Timothy Jay 
Published: February 2017

507 Background: ASPECCT demonstrated that panitumumab (pmab) was noninferior to cetuximab (cmab) for overall survival (OS). Ad hoc analyses from ASPECCT suggested that hypomag was associated with better outcomes for pmab and cmab (Price 2015). However, results from the phase 3 NCIC CTG/AGITG CO.17 trial indicated hypomag at day 28 was associated with worse outcomes for cmab (Vickers 2013). Methods: Patients (pts) with chemorefractory WT KRASexon 2 mCRC were randomized 1:1 to receive pmab or cmab. Ad hoc analyses by hypomag were performed from the final analysis of ASPECCT at week 5, consistent with the NCIC CTG/AGITG CO.17 trial analysis (Vickers, 2013). Results: 999 pts were treated: 496 received pmab and 503 received cmab. Any grade hypomag was 29.0% and grade ≥3 was 7.3% in the pmab arm vs 19.3% and 2.8% in the cmab arm, respectively. In the pmab arm, 1.2% of pts discontinued treatment and 5% of pts had dose modifications due to hypomag vs 0.4% and 3% in the cmab arm, respectively. Efficacy results by hypomag are shown (Table). Conclusions: In ASPECCT, rates of hypomag were higher in the pmab vs the cmab arm. Pts who developed any grade hypomag with pmab or cmab had longer median OS compared with those pts who did not. Consistent with previous analyses, development of hypomag at week 5 was associated with worse median OS for cmab. Clinical trial information: NCT01001377. [Table: see text]
To screen or not to screen: Colonoscopy, a story of successful population-based screening.
Authors: Mosquera Catalina , Lea C. Suzanne , Imai Satomi , Fitzgerald Timothy Louis 
Published: February 2017

508 Background: Screening for neoplasia of the breast and prostate has come under increasing scrutiny. However, little is understood regarding the temporal impact of screening on incidence and mortality for colorectal cancer (CRC). Methods: We selected states that had both CRC screening prevalence estimates from The Behavioral Risk Factor Surveillance System (BRFSS) and cancer registry data from The Surveillance, Epidemiology, and End Results (SEER) data from 1988-2012. We used SEER*Stat to compute age-adjusted incidence and mortality rates by state.Correlation coefficients were computed for change in screening. Results: The states California, Connecticut, Georgia, Hawaii, Iowa, New Mexico, and Utah were included. Each statehad unique population and tumor characteristics for age, gender, race, socioeconomic status, stage of presentation,and location of the primary, < 0.0001. Over the study period for ages 50 +, there was an increase in screening endoscopy (41 to 64%, R2 = 0.77, p < 0.0001) and a slight decrease in fecal occult blood testing (25 to 23%, R2 = 0.28, p < 0.0001). Similar trends were noted by state. There was an inverse relationship between increased screening endoscopy and incidence of CRC (60.03 to 34.68/100.000, R2 = 0.95 and p = < 0.0001); this was pronounced for early disease (45.4 to 25.7/100,000, p = < 0.0001) and minimal for late stage disease (10.5 to 7.2/100,000, p = 0.014). There was comparable trend in mortality (23.27 to 13.47 per 100.000). When evaluating states individually, the association between increasing endoscopic screening and the trends in incidence and mortality were robust (R2 0.75 – 0.92 and R2 0.65-0.95, respectively p < 0.0001). However, when states were analyzed collectively the association of screening with decreases in incidence and mortality was weaker (R2 = 0.27, p = 0.005 and R2 = 0.65, p = 0.06, respectively). Conclusions: Increased screening for CRC coincides with a decrease in incidence and mortality, disproportionality decreasing early stage cancer. This correlation is very strong within states but diminished between states, suggesting factors in addition to creening are influencing the epidemiology of CRC.