bluuebunny/crossref_metadata_2025_split huggingface dataset:
HSP90 expression and early recurrence in gastroenteropancreatic neuroendocrine tumors: Potential for novel therapeutic targets.
Authors: Ethun Cecilia Grace , Postlewait Lauren McLendon , Lopez-Aguiar Alexandra Grace , Zhelnin Kristen , Krasinskas Alyssa , El-Rayes Bassel F. , Russell Maria C. , Kooby David A. , Staley Charles A. , Cardona Kenneth , Maithel Shishir Kumar 
Published: March 2017

235 Background: Heat shock protein (HSP) 90 promotes tumor growth and is overexpressed in many malignancies. HSP90 expression profile and its potential as a therapeutic target in primary and metastatic neuroendocrine tumors (NETs) are not known. Methods: HSP90 cytoplasmic expression and Ki-67 index were re-reviewed and scored by a pathologist blinded to all other clinicopathologic variables using tissue microarray (TMA) blocks created in triplicate for patients who underwent resection of primary and metastatic gastroenteropancreatic (GEP) neuroendocrine tumors at a single institution from 2000-2013. Primary outcome was recurrence-free survival (RFS). Results: Of 278 tumors reviewed, 194 (68%) were primary GEP NETs, and 31 (11%) were NET liver metastases. Of the primary GEP NETs, mean age was 56yrs, 42% were male; 103 (53%) were pancreas and 44 (23%) were small bowel. HSP90 expression was high in 66 (34%) and low in 128 (66%). Compared to low expression, high HSP90 was associated with lymphovascular invasion (70vs42%; p = 0.049) and advanced T-stage (T3/T4: 48vs27%; p = 0.01). Among patients who underwent curative-intent resections for primary, non-metastatic NETs (n = 147), high HSP90 was associated with decreased 1-, 3-, and 5-yr RFS (80%, 72%, 62%) compared to low (89%, 86%, 83%; p = 0.03), which persisted on multivariable analysis (HR 5.2, 95%CI 1.7-16.0; p = 0.004), after accounting for positive margin, LN involvement, increased tumor size, site of primary tumor, and Ki-67 index. When assessing NET liver metastases, high HSP90 expression was seen in 4 (13%) patients and low in 27 (87%). Similar to primary GEP NETs, patients with liver metastases that exhibited high HSP90 expression had decreased 1-, 3-, and 5-yr progression-free survival (25%, 25%, 0%) compared to those with low HSP90 (69%, 49%, 33%; p = 0.052). Conclusions: Heat shock protein 90 exhibits differential expression in resected GEP NETs and liver metastases. High cytoplasmic expression is associated with early recurrence of disease, even after accounting for other adverse pathologic factors, including Ki-67 index. HSP90 inhibition is a potential target for novel therapeutic strategies for neuroendocrine tumors.
Second cancer risk after diagnostic and monitoring radiation exposure with computed tomography in patients with hepatocellular carcinoma.
Authors: Park Joong-Won , Ki Moran , Choi Hwa Young , Cho Hyunsoon , Lee Ju Hee , Koh Young Hwan 
Published: March 2017

238 Background: Contrast-enhanced dynamic computed tomography (CT) is preferred for initial diagnosis and post-treatment monitoring of hepatocellular carcinoma (HCC). The risk of a second cancer with diagnostic and monitoring CT radiation exposure in HCC patients is unclear. Methods: We analyzed cumulative radiation dose (CRD) for diagnostic and monitoring CT with/without transarterial chemoembolization (TACE) in patients with HCC alone (HA group) and HCC patients with a second cancer (SC group), using the big dataset of the National Health Insurance of South Korea. We performed survival analysis, with death treated as a competing risk. Results: A total of 20,073 patients with HCC were enrolled. With a median follow-up of 5.7 years, the SC group comprised 2,005 patients, resulting in a standardized incidence ratio of 1.5 (95% confidence interval [CI], 1.4-1.6) in men and 1.7 (95% CI, 1.6-1.9) in women, as compared with the general population. Use of CT/positron emission tomography (PET) was significantly higher in the SC group (p<0.001). However, the CRD of CT/PET was not significantly different between the SC group and the alive HA group (median effective dose [ED], 93 mSv for the SC group and alive HA group, respectively, p=0.510). After including TACE (n= 9,004 [44.9%], median frequency 2), total CRD was not significantly different between the SC group and the alive HA group. CRD >300 mSv significantly increased the risk of second malignant neoplasms in the subgroup with >7 years of follow-up (YFU) (hazard ratio [HR] 2.01, 95% CI 1.38-2.92, p<0.001). Second cancers in digestive organs and respiratory-intrathoracic organs were significantly increased by CRD in the subgroup with >300 mSv and over 7 YFU (HR 2.41, 95% CI 1.26-4.62; HR 5.69, 95% CI 1.62-20.04, respectively, p<0.01). TACE did not affect the increased risk of second cancers in digestive and respiratory organs in the subgroup >300 mSv and over 7 YFU. Conclusions: The risk of second cancers increased in HCC patients who survived over 7 years with CRD >300 mSv. Consideration of alternative monitoring tests and guidelines for reducing radiation exposure is crucial for long-term HCC survivors.
Long-term quality of life comparison after endoscopic submucosal dissection versus surgery in early gastric cancer patients.
Authors: Kim Young-Il , Kim Young Ae , Kim Chan Gyoo , Ryu Keun Won , Kim Young Woo , Sim Jin Ah , Yun Young Ho , Choi Il Ju 
Published: March 2017

24 Background: The aim of this study was to compare the serial changes of health-related quality of life (HRQOL) after Endoscopic submucosal dissection (ESD) with those after surgery in patients with early gastric cancer (EGC). Methods: Gastric cancer patients were prospectively enrolled from 2004 through 2007. HRQOLs of 161 EGC patients were prospectively assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) and the stomach cancer-specific module EORTC-QLQ-STO22 at the baseline, 1, 6, 12, 18 and 24 months after treatments. Analysis was done using the generalized linear model and paired- ttests. Results: Of 161 patients, 48 (29.8%) underwent ESD (ESD group) and 113 (70.2%) underwent surgery (surgery group). The median age of stomach cancer patients was 57 years. Surgery group had poorer scores compared with those of ESD group in the most HRQOL factors one month after treatments ( P< 0.05), except for emotional and cognitive functioning, financial problems, anxiety, and hair loss. However, most of the functional and symptom scales after surgery subsequently improved and became insignificant until 24 months of follow up. Only 3 parameters including physical functioning, diarrhea and body image in ESD group still remained better until 24 months after treatment ( P< 0.05). Conclusions: Because poorer HRQOLs after surgery in the early post-treatment periods become insignificant during long-term follow-up, surgical treatment should not be discouraged in EGC treatment solely based on the QOL aspects.
Clinical features and tumor mutational profile of younger versus older patients with cholangiocarcinoma (CCA).
Authors: Goyal Lipika , Reyes Stephanie , Jain Apurva , Shroff Rachna T. , Le Tri Minh , Rahma Osama E. , Kelley Robin Kate , Bocobo Andrea Grace , Kanakamedala Advaita , Boyhen Kylie , VanCott Christine , Lindsey Stacie , Zheng Hui , Zhu Andrew X. , Javle Milind M. 
Published: March 2017

240 Background: As seen in lung cancer, young patients with cancer can have different risk factors, presentation, and tumor genotype than older patients with the same disease. The clinical and molecular features of young patients with CCA have yet to be well characterized. Methods: Retrospective chart review was performed on patients with intrahepatic (ICC) or extrahepatic cholangiocarcinoma (ECC) across 5 institutions. Data on demographics, risk factors, treatments, pathology, and overall survival (OS) were collected. Tumor genotyping results from MGH SNaPShot and Foundation Medicine were analyzed. Log-rank tests and Kaplan-Meier survival curves were used for statistical analysis. Results: Of 567 patients analyzed, 134 (23.6%) were < 50 years old (yo) and 455 (80.2%) had ICC. When assessed for risk factors, younger patients ( < 50yo) were more likely to have primary sclerosing cholangitis (PSC) (p < 0.001) and less likely to have diabetes (p = 0.05), compared to older patients ( ≥ 50yo). Surgical resection rates were similar in younger vs older patients (41.9 vs 42.6%, p = 0.890), but younger patients had larger tumors (median size 7.1 vs 5.3cm p = 0.012). Younger patients were also more likely to receive palliative systemic chemotherapy (p < 0.001) and more lines of therapy (median, 2 vs 1 line, p < 0.001). Frequency of treatment with liver directed therapy did not differ between the two groups. Molecular testing was performed on 222/567 (39.1%) patients of which 84/134 (62.7%) were younger patients and 138/433 (31.9%) were older patients. FGFR aberrations were more common in younger patients versus older patients (17.6 vs. 5.7%, p = 0.002). Targeted therapy was given to 15/84 (17.9%) younger and 28/138 (20.3%) older patients based on results of mutational profiling. Finally, no significant difference was seen in OS between younger and older patients (22.9 vs 22.7 months, p = 0.89). Conclusions: Younger patients with CCA may have different risk factors, tumor biology, and tolerance of systemic therapy compared to older patients. Further study is needed as referral patterns to tertiary care centers and motivation of younger patients to seek tertiary care may impact these results.
Real-world evidence (RWE) to show improved time to progression among resected pancreatic cancer (RPC) patients receiving adjuvant chemotherapy (adjch).
Authors: Kish Jonathan , Feinberg Bruce A. , Maida Tracy , Biggs Craig , Mujumdar Urvi , Chopra Dhruv , Laney Jalyna R. , Kennedy Eugene 
Published: March 2017

242 Background: Two recent clinical trials (IMPRESS and APACT) suggest the overall survival (OS) of patients with resected pancreatic cancer (RPC) is far longer than previously believed. Improvements in patient selection, intra/post-operative surgical care adjch are suggested as explanations for the improved OS. RWE of time to progression (TTP) from surgery were calculated to assess if the results of these trials are generalizable. Methods: RPC patients (ICD-9=157.x, excluding 157.4; CPT=48140, 48146, 48150, 48152-5) diagnosed between 03/2012-06/2015 were selected from the Inovalon More2 administrative claims database. Adjch was defined as initiating chemotherapy within 90 days of surgery. TTP was the time from surgery until the first claim for metastatic disease (ICD-9 =196.0-.3, .5-.6, 197.0-.8, 198.0-.8) using the Kaplan-Meier method. Patients without a metastatic diagnosis during their follow-up were censored at 12 months to adjust for underreporting of metastatic disease codes in claims. Results: 1,014 RPC patients selected. Mean follow-up time was 12.9 months (SD = 10.8). Mean age at diagnosis was 62.7 years (SD = 13.0) and 39.7% (n=403) had commercial insurance, 40.9% (n=415) Medicare and 18.5% (n=188) Medicaid. Of all RPC patients, 54.4% (n=552) received any chemotherapy of which 59.8% (n=330) was adjch; 37.4% (n=379) were diagnosed with metastatic disease at the time of or following resection. The rate of progression events was 40.5% (n=277) without adjch and 30.9% (n=102) with adjch (p<0.01). Among all resected patients, median TTP was 15.7 months (95% CI: 13.8-26.0) with 93.7% (n=355) of progression events by 12 months. Median TTP was 20.4 months (95% CI: 15.5-NR) in patients receiving adjch vs 17.7 months (95% CI: 17.7-31.5) without adjch (p=<0.0001). Conclusions: This analysis demonstrated a 2.7 month longer TTP for patients who received adjch compared to those who did not (p<0.0001). The median TTP in both adjch and non-adjch groups was longer than the observed in the ESPAC-1 trial for adjch patients TTP (15.3 months) and OS (20.1 months). These data support a new baseline for efficacy in adjch trials and are in line with more recent RCT estimates.
Incidentally discovered pancreatic ductal adenocarcinoma: Is detection of asymptomatic cancer associated with better outcomes than symptomatic cancer?
Authors: Takeda Yoshinori , Saiura Akio , Mise Yoshihiro , Ishizawa Takeaki , Inoue Yosuke , Takahashi Yu , Ito Hiromichi 
Published: March 2017

243 Background: The number of incidentally discovered asymptomatic pancreatic ductal adenocarcinoma (APDAC) has been increasing along with recent wide spread use of imaging studies in general practice. However, the clinical implication in early detection of asymptomatic pancreatic cancer remains yet to be determined. In this study, we reviewed our experience of patients with PDAC in high volume cancer center and compared the characteristics and long-term outcomes between those with APDAC and symptomatic PDAC (SPDAC). Methods: This retrospective study included 569 consecutive patients with PDAC initially treated in our institution from January 2007 to December 2012. Median follow-up period was 29 months for the survivors. Two hundred and fifty patients underwent surgical resection and 319 patients were deemed unresectable. The patient’s demographics, tumor locations, pathologic stages, and treatment type received, and the overall survival (OS) were compared between the patients with APDAC and those with SPDAC. Results: One hundred and sixty-three patients (29%) presented without any subjective symptoms. When compared with SPDAC, APDAC was associated with early stage (stage I, 6% vs. 1%, p<0.01). Among 163 patients with APDAC, 104 patients (64%) underwent surgical resection, while only 146 patients (36%) out of 406 SPDAC underwent resection ( p<0.01). The 5-year OS rate of the patients with APDAC was 18%, comparing with 7% for those with SPDAC ( p<0.01). Among the patients who underwent resection, the presence of symptoms did not affect the chance of incomplete resection (R1, 12% vs. 22% for patients with APDAC and SPDAC, respectively, p=0.06) and the 5-year OS rate (23% vs. 22%, p=0.09). However, the patients with SPDAC required complex operation (concomitant vascular resection and reconstruction 56% vs. 29% for those with APDAC, p<0.01). Conclusions: Asymptomatic PDAC is associated with better long-term outcomes than symptomatic PDAC due to early stage at presentation and higher chance of resectability. Our findings highlight the potential implication of screening program for early detection of PDAC for selected high-risk patient population.
Multigene hereditary cancer panel testing for patients with pancreatic cancer.
Authors: McGill Anna K , Solomon Sheila R , Marshall Megan L , Susswein Lisa , Fillman Corrine , Skora Katherine A , Vogel Postula Kristen J , Klein Rachel , Hruska Kathleen S. , Xu Zhixiong 
Published: March 2017

244 Background: Pancreatic ductal adenocarcinoma (PC) is associated with multiple hereditary cancer syndromes. Genes implicated in hereditary PC include ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2 and PMS2. The advent of multi-gene hereditary cancer panel testing streamlines diagnoses and medical management for clinicians and patients. Our objective was to assess the yield of pathogenic/likely pathogenic variants (PV/LPV) in individuals with PC undergoing panel testing as an initial test at GeneDx. Methods: We retrospectively reviewed panel test results of 605 individuals reporting a personal history of PC. Panel testing evaluated up to 32 genes associated with hereditary cancer. Individuals reporting neuroendocrine pathology or previous BRCA1/BRCA2 testing were excluded. Results: In this cohort, 61 PV/LPV were detected in 57 individuals in the following genes: ATM (17), BRCA2 (14), BRCA1 (5), CDKN2A (5), PALB2 (5), CHEK2 (4), MLH1 (2), MUTYH (2), PMS2 (2), BARD1 (1), FANCC (1), MSH2 (1), RAD51D (1) and TP53 (1), corresponding to a positive yield of 9.4% (57/605). Fifty-one of 61 PV/LPV were detected in genes associated with PC (84%) while 10 PV/LPV (16%) were identified in other genes including BARD1, CHEK2, FANCC, MUTYH, and RAD51D. The diagnostic yield among those reporting a family history of PC (33/294, 11.2%) was not statistically different from those without a reported family history (24/311, 7.7%). However, PV/LPV in ATM were detected more often in individuals reporting a family history of PC compared to those without a family history (4.1% vs. 1.6%, p=0.018). Conclusions: In total, 9.4% of patients with PC tested positive for PV/LPV in 14 different genes by panel testing. Although the majority of PV/LPV were identified in known PC genes, 16% of positive findings occurred in genes not typically associated with PC. ATM was most commonly implicated and more frequently reported in patients reporting family histories of PC. Assessing whether these genes are indeed causally related to PC and/or are possibly associated with other cancer types requires further investigation. Based on our results we conclude multi-gene panel testing may be considered as a first option for patients with PC regardless of their family history.
A population-based study of biliary tract cancers (BTCs) in Alberta, Canada: How do our patients fare?
Authors: Lui Arthur Gregory Ang , Yusuf Dimas , Randolph Brock , Tam Vincent C. , Bathe Oliver F. , Ghosh Sunita , Spratlin Jennifer L. 
Published: March 2017

246 Background: BTCs are poorly studied due to their rarity and heterogeneity. We explored demographics and outcomes of BTC pts over a 15 year period. Methods: All patients (pts) with biopsy-proven BTC (intrahepatic [IC] and extrahepatic [EC] cholangiocarcinomas, gallbladder cancers [GB], and ampulla of vater cancers [AV]) in Alberta were reviewed from January 1, 2000, to December 31, 2015. Demographic, pathologic, and survival data were extracted from electronic charts. Descriptive statistics were utilized. Overall survival (OS) was defined as the time from pathologic diagnosis to death date. Results: A total of 1,718 pts with BTCs were identified. Median age was 68 with 52% being male. The Table demonstrates OS breakdown based on tumour location and stage. Regardless of location of primary tumour, grade impacted survival (median OS in with well differentiated tumours vs undifferentiated tumors 26.6 vs 3.9 months). Pts who received standard of care palliative cisplatin/gemcitabine (Cis/Gem) chemotherapy (n = 123) had a median OS of 15.4 months. Conclusions: Patients with AV and IC have the best and worst prognosis, respectively. Shorter survival is observed with higher stage, grade, and unresectable disease. Pts who received palliative Cis/Gem had better OS than reported in the pivotal phase III trial. Further analysis of prognostic factors will be presented. [Table: see text]
Racial and ethnic disparities among young patients with gastric cancer.
Authors: Nassour Ibrahim , Mokdad Ali , Khan Madiha , Mansour John C. , Yopp Adam Charles , Minter Rebecca M , Polanco Patricio , Augustine Mathew M , Choti Michael A. , Wang Sam C. , Porembka Matthew 
Published: March 2017

25 Background: Although up to 15% of patients with gastric cancer present at young age, the characteristics of these patients are not well described. We sought to determine if there are different clinical and pathologic characteristics associated with race and ethnicity in young gastric cancer patients. Methods: We identified all gastric adenocarcinoma patients who were younger than 45 years in the National Cancer Data Base between 2006 and 2013. We analyzed patient, tumor, and treatment-related factors as well as overall survival using standard statistical methods. Results: 5,869 patients were identified with 40.6% being Non-Hispanic Whites (NHW), 27.7% Hispanics (HS), 16.9% African Americans (AA), and 9.0% Asians (AS). HS patients presented at a younger age compared to the other groups (p < 0.01). HS presented most often with metastatic disease (59.2%) followed by AA (50.2%), NHW (49.6%), and AS (49.8%; p < 0.01). NHW presented more often with tumors in the cardia (45.7%) compared to AA (12.7%), HS (12.5%), and AS (9.6%, p < 0.01). HS (28.4%) and AA (14.2%) were more likely to be uninsured compared to AS (12.0%) and NHW (7.1%; p < 0.01). AA (60.5%) and HS (49.1%) were more likely to have below median income compared to NHW (35.8%) and AS (24.2%, p < 0.01). AS had better overall outcome, with median overall survival of 22.7 months compared to 15.2 months for NHW, 14.0 months for HS and 13.6 months for AA (p < 0.01). Independent variables associated with favorable survival included being AS or HS, cardia tumor, treatment at an academic center, higher income, and low Charlson Comorbidity Index. Conclusions: There is racial/ethnic variability in disease presentation, treatment delivery, and outcomes in young gastric cancer patients. Further studies are warranted to determine whether these variations are due to disparity in health care access and/or inherent difference in biology.
Impact of BRCAness on the efficacy of oxaliplatin-based chemotherapy in patients with unresectable pancreatic cancer.
Authors: Kondo Tomohiro , Kanai Masashi , Kou Tadayuki , Sakuma Tomohiro , Mochizuki Hiroaki , Kamada Mayumi , Nakatsui Masahiko , Uza Norimitsu , Kodama Yuzo , Masui Toshihiko , Takaori Kyoichi , Matsumoto Shigemi , Miyake Hidehiko , Okuno Yasushi , Muto Manabu 
Published: March 2017

250 Background: Defects in individual genes that are involved in homologous recombination repair (HRR) is called “BRCAness” and several studies suggested that patients with BRCAness are more sensitive to platinum-based chemotherapy (Golan et al, 2014; Lowery et al, 2011; Vollebergh et al, 2014). We introduced the multiplex gene panel test into daily clinical practice since April 2015 at Kyoto University Hospital, in which we can monitor the entire coding region of 215 cancer-related genes and the rearrangement of 17 frequently rearranged genes. The purpose of this study was to evaluate the association between BRCAness status monitored by multiplex gene panel test and clinical outcome of patients with unresectable pancreatic ductal adenocarcinoma (PDAC) who received oxaliplatin-based chemotherapy. Methods: A total of consecutive 17 patients with histologically confirmed PDAC who underwent multiplex gene panel test were eligible. BRCAness status was determined according to the results of multiplex gene panel test. Oxaliplatin-based chemotherapy included FOLFIRINOX, GEMOX and SOX. We assessed the time to treatment failure (TTF) to evaluate the efficacy of oxaliplatin-based chemotherapy by log-rank test. Results: BRCAness-related mutations were detected in BRCA2 (n = 6), ATM (n = 4), ATR (n = 2), BRCA1 (n = 2), and PALB2 (n = 1). Based on these results, 11 patients were classified into non-BRCAness group and six patients were into BRCAness group. Seven and five patients received oxaliplatin-based chemotherapy in non-BRCAness and BRCAness group, respectively. Median TTF of oxaliplatin-based chemotherapy was 52 days (95% confidence interval [CI], 40–90 days) in non-BRCAness group and 294 days (95% CI, 56 days–NA) in BRCAness group. The difference was statistically significant (P = 0.027). Of note, two patients with BRCAness showed good response to FOLFIRINOX without disease progression > 500 days. Conclusions: BRCAness-related mutations could be a promising predictive marker of the efficacy of oxaliplatin-based chemotherapy.