bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional differences in efficacy/safety/biomarkers in a randomised study of axitinib in 2nd line patients (pts) with advanced hepatocellular carcinoma (HCC).
Authors: Kudo Masatoshi , Park Joong-Won , Obi Shuntaro , Qin Shukui , Assenat Eric , Umeyama Yoshiko , Chakrabarti Debasis , Valota Olga , Fujii Yosuke , Martini Jean-Francois , Williams James Andrew , Kang Yoon-Koo 
Published: February 2017

329 Background: A randomised, double-blind phase II study of axitinib plus BSC [AXI] vs placebo plus BSC [PBO] was conducted in HCC pts after failure of one antiangiogenic therapy. Primary outcome was presented at ESMO 2014. No significant differences in overall survival (OS) between two arms were noted overall and in pre-specified subgroup analysis (non-Asian [nA] and Asian [A]). Interestingly, improvements favouring AXI (P < 0.01) were observed in secondary efficacy endpoints and retained among A. Methods: Exploratory efficacy/safety/biomarker analyses were performed by geographic region (nA; A; A subgroups: Japan/Korea [JK] and China/Hong Kong/Taiwan [CHT]) including: OS excluding pts intolerant to prior therapy; relationship between a subset of 26 baseline micro RNAs (miR) and AXI effect. Results: 78 nA pts (76% male, 60% with vascular invasion/extrahepatic spread) and 124 A pts (73JK/51CHT) (86% [84% JK, 90% CHT] male; 86% [82% JK, 92% CHT] with vascular invasion/extrahepatic spread) were randomized. In regional subgroups, OS HR excluding pts intolerant to prior therapy was: nA HR = 0.700 (95% CI 0.373–1.316; p = 0.1318) for AXI (45) vs PBO (16); A HR = 0.653 (95% CI 0.415–1.027; p = 0.0312) for AXI (76) vs PBO (35); JK HR = 0.479 (95% CI 0.250–0.918; p = 0.0118) for AXI (46) vs PBO (17); CHT HR = 0.918 (95% CI 0.480–1.756; p = 0.3954) for AXI (30) vs PBO (18). AXI safety profile was generally similar in regional subgroups. Differences were seen in dose modification pattern: dose reduction or discontinuation due to adverse events in 24% nA / 41% A / 51% JK / 26% CHT or in 39% nA / 22% A / 16% JK / 32% CHT, respectively. miR analysis for OS showed a trend of predictive and/or prognostic effect in overall population (e.g., let-7e-5p); a strong predictive effect of multiple miR (e.g., miR-3648) was seen in A but not in nA. Conclusions: AXI showed favorable OS vs PBO in nA and A, particularly in JK, when pts intolerant to prior therapy were excluded, suggesting that pts who progress on prior therapy are more suitable population for new agent studies in HCC. Appropriate dose modifications may also play a role in treatment duration. Baseline miR signature may have predictive value for AXI OS in A. Clinical trial information: NCT01210495.
Staging laparoscopy with cytology analysis in gastric cancer.
Authors: Ikoma Naruhiko , Elimova Elena , Blum Mariela A. , Ajani Jaffer A. , Chiang Y. Sabrina , Fournier Keith F. , Mansfield Paul F. , Badgwell Brian D. 
Published: February 2017

35 Background: The purpose of this study was to identify clinicopathologic factors associated with the identification of peritoneal disease in patients with gastric cancer and to compare the yield of laparoscopy over time. Methods: The medical records of 7,404 patients with gastric or gastroesophageal adenocarcinoma presenting to our institution (1/1995 to 12/2012) were reviewed to identify patients who underwent diagnostic laparoscopy as a staging procedure before treatment. Associations between clinicopathologic factors and peritoneal disease were examined with chi square and logistic regression analysis. The yield on laparoscopy was stratified according to time. Results: We identified 880 patients who underwent staging laparoscopy for gastric adenocarcinoma. Excluded patients included those with recurrent gastric cancer, those who underwent prior chemotherapy and/or radiation therapy, those with known distant metastatic disease (except for equivocal radiological findings), and those who underwent procedures not for staging purposes, leaving 711 patients in this study: 43.5% with gastroesophageal junctional tumors, 72.9% with poorly differentiated adenocarcinoma, and 53.0% with signet ring cell morphology. Endoscopic ultrasound (EUS) most commonly identified T3 (83.9%) and N-positive (66.4%) tumors. As results of laparoscopy, 148 patients (20.8%) were found to have macroscopic peritoneal carcinomatosis. Among 514 macroscopically negative patients who had peritoneal lavage cytology analysis, 68 (13.2%) were found to have positive. Of the 711 study patients, 42 (5.9%) had other unexpected clinically important findings (e.g., distant metastasis, cirrhosis). Multivariate analysis showed a high positive rate of laparoscopy in patients with poorly differentiated pathology, linitis plastica, or equivocal CT scan, after adjusting race, signet ring cell, and tumor location. The yield of laparoscopy did not change over time when divided into three 6-year periods (p = 0.58). Conclusions: Laparoscopy remains an important staging procedure to evaluate for peritoneal spread when considering treatment or surgery, even in the current era of high-quality imaging evaluation.
Splenic radiation during pancreatic cancer radiotherapy: Are we throwing the baby out with the bath water?
Authors: Chadha Awalpreet Singh , Liu Guan , Arora Harpreet Kaur , Thames Howard D , Krishnan Sunil 
Published: February 2017

354 Background: Lymphopenia is commonly seen following chemoradiation and is associated with a poor prognosis. We conducted this study to determine if the severity of lymphopenia is dependent on the radiation dose and the fractional volume of spleen irradiated unintentionally during definitive chemoradiation in patients with locally advanced pancreatic cancer (LAPC). Methods: 177 patients with LAPC were treated with induction chemotherapy (FOLFIRINOX or gemcitabine- based regimens) followed by chemoradiation (CRT; median 50.4 Gy with concurrent capecitabine) from 1/2006 to 12/2012. Absolute lymphocyte count (ALC) was recorded at baseline, prior to CRT and 2-10 weeks after the end of CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and the percentage of splenic volume receiving at least 5 Gy (V5), 10 Gy (V10), 15 Gy (V15) and 20 Gy (V20) dose. Overall survival (OS) was analyzed using Cox model and multivariate logistic regression was used to assess the development of post CRT severe lymphopenia (ALC < 0.5 K/UL) using baseline and treatment factors. Results: Median post-CRT ALC (0.68 K/UL, range 0.13 to 2.72) was significantly lower than both baseline (1.42 K/UL, range 0.34- 3.97; p < 0.0001) and pre-CRT ALC (1.32 K/UL, range 0.36- 4.82; p < 0.0001). Post-CRT ALC < 0.5 K/UL was associated with inferior OS on univariate (16.8 vs. 21.2 months, p = 0.004) and multivariate analysis (HR = 1.9, p = 0.002).The MSD was 8.8 Gy and log MSD showed a significant negative correlation (r = -0.18, p = 0.02) with post-CRT ALC. Median V5, V10, V15 and V20 were 34%, 21%, 13% and 8% respectively. Median V10 (32.6 vs. 16%, p = 0.04), V15 (23.2 vs. 9.5%, p = 0.03) and V20 (15.4 vs. 4.6%, p = 0.02) were significantly higher in patients with severe lymphopenia. On multivariate logistic regression analysis, baseline lymphopenia (ALC < 1 K/UL; p = 0.003, OR = 4.6) and MSD (p = 0.03, OR = 7.3) were independent predictors for the development of severe post-CRT lymphopenia. Conclusions: LAPC patients receiving high MSD during CRT are at increased risk of developing severe lymphopenia, which is an independent predictor of poor OS. Routine assessment of splenic DVHs prior to acceptance of treatment plans may minimize this risk.
Role of adjuvant therapy after R0 resection for patients with distal cholangiocarcinoma.
Authors: Kim Young Saing , Hwang In Gyu , Park Song-ee , Kim Eun Young , Kang Jung Hun , Go Se-Il , Park Inkeun , Oh Sung Yong , Ji Jun Ho , Song Haa-na , Park Se Hoon , Kim Seung Tae 
Published: February 2017

355 Background: There is still debated regarding the optimal treatment strategy in cholangiocarcinoma after curative resection. The aim of this study was to analyze the role of adjuvant therapy in R0-resected distal cholangiocarcinoma. Methods: We retrospectively reviewed the medical records of patients who underwent R0 resection for distal cholangiocarcinoma between January 2001 and December 2013 at six cancer centers in Korea. Adjuvant therapy consisted of chemotherapy (CT), chemoradiotherapy (CRT), or radiotherapy (RT). Multivariable Cox proportional hazards model was used to identify prognostic factors for overall survival (OS). Results: A total of 158 patients were included in the analysis; 47 patients (29.7%) had lymph node involvement. Fifty-six patients (35.4%) received adjuvant therapy (CT/CRT/RT: 27/20/9, respectively). Patients with advanced TNM stage (p = 0.001), T3/T4 disease (p = 0.009), positive lymph nodes (p = 0.052) and elevated CA 19-9 (p = 0.071) were more likely to receive adjuvant therapy. The effect of adjuvant therapy varied according to the treatment modality. Multivariable analysis showed a significant improvement in OS with CRT (Hazard ratio (HR) 0.25, 95% CI 0.08-0.83, p = 0.024) and CT (HR 0.21, 95% CI 0.08-0.53, p = 0.001). However, RT alone was associated with shorter OS (HR 2.38, p = 0.040), along with T3/T4 disease (HR 2.12, p = 0.012) and positive lymph nodes (HR 2.30, p = 0.008). In the subset analysis according to lymph node status, adjuvant therapy not including RT alone was associated with a significant OS advantage both in node-negative patients (median, 103.3 vs. 54.9 months, p = 0.037) and node-positive patients (not reached vs. 22.6 months, p = 0.013). Conclusions: Our results showed that patients receiving adjuvant CT or CRT had significant improvement in OS. In addition, the benefit of adjuvant therapy (except RT alone) was observed even in patients with negative lymph nodes.
The impact of maximum tumor shrinkage of primary site (MTSP) by FOLFIRINOX in the first-line treatment of pancreatic cancer.
Authors: Saito Kei , Ozaka Masato , Kanata Ryo , Yamada Ikuhiro , Sasaki Takashi , Matsuyama Masato , Takano Kouichi , Sasahira Naoki 
Published: February 2017

356 Background: FOLFIRINOX is the first-line chemotherapy for patients with unresectable pancreatic cancer and yielded a longer overall survival, a superior progression-free survival, a higher objective response rate compared with gemcitabine alone. Maximum tumor shrinkage of primary site (MTSP) was associated with the survival outcome in colon cancer. However the data of tumor shrinkage in pancreatic cancer has not been well-documented. Therefore, we re-evaluated FOLFIRINOX focusing on the tumor shrinkage of primary site. We also assessed impact of tumor shrinkage on survival of unresectable pancreatic cancer. Methods: Medical records were retrospectively reviewed for consecutive patients receiving FOLFIRINOX as the first-line chemotherapy between January and December 2014. Response was evaluated by CT scan every 2 or 3 months until the end of treatment. We analyzed patients’ characteristics and rate of MTSP related to overall survival (OS) and progression free survival (PFS). Results: Thirty one patients were analyzed: median age of 62, male gender in 64.5%, performance status of 0 in 90.3%, metastatic cancer in 58.1%, the head of cancer in 41.9%, the UGT1A1 wild type in 48.4%, overall response rate in 25.8%. PFS was 7.7 months (95%CI: 6.57-9.6). Rate of MTSP were 18.8% (locally 18.8%, metastatic 18.1%) and rate of GRs/non-GRs/non-R (GRs (Good responders) were defined as patients whose MTSP were more than 20% and non-GRs (non-Good responders) were less than 20%) were 45.2%/35.5%/19.3%. PFS was 9.0(95%CI, 6.7- ) months in GRs, compared with 6.9(95%CI, 3.6-10.2) months in non-GRs (p = 0.15). Conclusions: MTSP by FOLFIRINOX could not affect PFS of pancreatic cancer.
Impact of radiation and surgery for intraductal papillary neoplasm of the bile duct: A population-based analysis.
Authors: Szeja Sean , Dandapani Savita V. , Swanson Todd A. 
Published: February 2017

363 Background: Intraductal Papillary Neoplasm of the Bile Duct (IPNB), either in-situ or invasive, is a histological variant with better prognosis then the more common adenocarcinoma. This study’s purpose is to use the Surveillance Epidemiology and End Results (SEER) database to evaluate prognostic factors: histology, stage, location, extent of surgery and the use of radiation therapy (RT). Methods: Cases from 1973-2011 were acquired. Inclusion criteria included intrahepatic (IHD), extrahepatic bile duct (EHD) or ampulla of vater (AoV) locations, first primary, extent of surgery and RT history. Kaplan-Meier and Log-Rank methods measured overall survival (OS) and disease specific survival (DSS) in months (m) and their medians (MOS, MDSS). Cox multivariate regression computed hazard ratios (HR) controlling for stage, treatment, surgical extent and histology. Results: . For non-invasive cases, 14% were IPNB (n = 31). Survival was similar for EHD & AoV cases. Surgery was associated with prolonged MOS of 120m compared to 8m without surgery or RT. A trend suggested better survival with lesser extent of surgery for EHD & AoV cases (p < 0.16, n = 8 at both sites). For invasive cases, 5% were IPNB (n = 1309). For cases not receiving surgery, RT was associated with prolonged OS & DSS from 3 to 7m (p = 0.026) and 4 to 8m (p = 0.074). In T1N0M0 EHD cases, surgery with and without RT had similar OS & DSS. Cox analysis observed similar OS & DSS for surgery with and without RT for EHD and AoV cases. Mucin-producing IPNB was less likely local stage disease (10% vs 39%, p < 0.01), with shorter OS 5m vs 23 m (p < 0.01) and DSS 6m vs 28m (p < 0.01), and for EHD cases, with HR = 2.0 (p < 0.01) compared to papillary type IPNB. Conclusions: For non-invasive IPNB, surgery with less extensive resections was associated with better prognosis. For invasive IPNB cases not amenable to surgery, RT improved short term survival. If high-risk factors such as suboptimal surgical margins, which are not recorded in SEER, correlated with the use of RT, then the outcomes in EHD & AoV locations could be explained by an imparted benefit. As well, mucin-associated IPNB, was associated with worse survival than papillary type. Further work is necessary to validate these findings.
Optimal prognostic lymph node staging system for gallbladder adenocarcinoma: A multi-institutional study.
Authors: Amini Neda , Kim Yuhree , Wilson Ana , Ethun Cecilia Grace , Maithel Shishir Kumar , Poultsides George A. , Tran Thuy , Idrees Kamran , Isom Chelsea A , Fields Ryan C. , Weber Sharon M. , Salem Ahmed Abdel-Fattah , Martin Robert C. G. , Scoggins Charles Raben , Shen Perry , Mogal Harveshp , Schmidt Carl Richard , Hatzaras Ioannis , Shenoy Rivfka , Pawlik Timothy M. 
Published: February 2017

364 Background: The American Joint Committee on Cancer (AJCC) classification is the most universally accepted lymph node (LN) staging system for gallbladder adenocarcinoma (GBA); however, it focuses more on location of LN metastasis than number of LN metastasis. Other lymph node staging systems have been proposed for GBA. We therefore sought to examine the performance of different staging systems including AJCC LN staging system, number of metastatic LN (NMLN), log odds of metastatic LN (LODDS), and LN ratio (LNR). Methods: Patients who underwent curative-intent resection for GBA between 2000 and 2015 and who had lymphadenectomy were identified from a multi-institutional database. The prognostic performance of four staging systems was compared by Harrell’s C and Akaike information criterion (AIC). Results: Overall 214 patients with a median age of 66.7 years (IQR 56.5, 73.1) were identified. A total 1,334 LNs were retrieved from 214 patients, with a median of 4 (IQR 2-8) LNs per patient. In the study cohort, 98 (45.5%) patients had LN metastasis with total of 271 positive LNs [median of 1 (IQR 1-3)]. Patients with LN metastasis had an increased risk of death (HR 1.87, 95%CI 1.24-2.82; P = 0.003). In addition, risk of death increased by each additional LN metastasis (HR 1.20, 95%CI 1.06-1.37; P = 0.005). In the entire cohort, LNR, in either a continuous (C-index: 0.603, AIC: 808.4) or a discrete scale (C-index 0.609, AIC 802.2), provided better discrimination versus LODDS, AJCC LN staging system, and NMLN. The relative performance of all scoring systems was better among patients who had ≥ 4 LN examined. In the cohort of patients with ≥ 4 LN examined, LODDS (C-index 0.621, AIC 363.8) had the best performance compared with LNR (C-index 0.615, AIC 368.7), AJCC LN staging system (C-index 0.601, AIC 373.4), and NMLN (C-index 0.613, AIC 369.5). Conclusions: LODDS and LNR performed better than the AJCC LN staging system. Among those who had more LN examined, LODDS performed better than LNR. LODDS and LNR should be incorporated into the AJCC LN staging system of GBA.
Effect of time to initiation of adjuvant chemotherapy on survival in resected pancreatic cancer.
Authors: Mirkin Katelin Anne , Hollenbeak Christopher S , Wong Joyce 
Published: February 2017

368 Background: Pancreatic cancer carries a grim prognosis. Surgical resection followed by adjuvant chemotherapy is standard of care, but little is known about the temporal relationship of chemotherapy initiation and survival. This study analyzed the impact of time to initiation of adjuvant chemotherapy on survival in patients with resected pancreatic cancer. Methods: The National Cancer Data Base (2003-2011) was retrospectively reviewed for patients with clinical stages 1-3 resected pancreatic carcinoma. Time to chemotherapy was stratified at the 12-week post-operative timepoint. Univariate statistics, Kaplan-Meier estimates, and Cox proportional hazard modeling were performed. Results: 5,205 patients who had undergone surgical resection alone, 3,144 patients who had undergone surgical resection and adjuvant chemotherapy initiated at or before 12 weeks, and 906 patients who had undergone surgical resection followed by adjuvant therapy started after 12 weeks were included. Patients who received chemotherapy > 12 weeks tended to be older, have more co-morbidities, receive treatment at academic centers, and undergo whipple procedures. In all pathologic disease stages, adjuvant chemotherapy conferred a significant survival benefit over surgical resection alone (p < 0.0001). However, there was no significant overall survival benefit for patients receiving adjuvant chemotherapy before 12 weeks as compared to after (p = 0.85). When stratified by pathological stage, there was still no significant survival benefit for earlier initiation of chemotherapy (£ vs. > 12 weeks): stage I, p = 0.16, stage II, p = 0.12, stage III, p = 0.38. After controlling for patient, disease, and surgery characteristics, patients who received adjuvant chemotherapy after 12 weeks had a 31% lower odds of mortality at 5 years, while those who initiated it before 12 weeks had a 34% lower odds (p < 0.0001, p < 0.0001 respectively), versus surgery-alone. Conclusions: Earlier initiation of adjuvant chemotherapy does not significantly impact long-term survival in patients with resected pancreatic cancer. However, because adjuvant chemotherapy confers a survival benefit, delayed chemotherapy should be offered when appropriate.
Clinical outcomes of resectable small bowel adenocarcinoma treated by surgery alone: Case series in a Japanese single institution.
Authors: Noda Shoko , Honma Yoshitaka , Moro Hiroshi , Nakamura Shoko , Sasaki Yusuke , Takahashi Naoki , Iwasa Satoru , Okita Natsuko , Takashima Atsuo , Kato Ken , Hamaguchi Tetsuya , Boku Narikazu , Esaki Minoru , Shimada Kazuaki , Morita Shinji , Fukagawa Takeo , Katai Hitoshi 
Published: February 2017

372 Background: Small bowel adenocarcinoma (SBA) is known as a poor prognostic cancer even in surgically resected cases. Its five-year survival rates were reported as 65%, 48%, and 35% in stage I, II, and III SBA, respectively. However, clinical outcomes of curatively resected SBA, especially without peri-operative adjuvant chemotherapy, are still unknown in Japanese population. Methods: We retrospectively reviewed medical records of patients who were diagnosed as Stage I, II, and III SBA after curative surgery between July 1994 and June 2014 at National Cancer Center Hospital. Overall survival (OS) and relapse-free survival (RFS) were calculated by Kaplan-Meier method. Cox proportional-hazards analysis was performed to identify the prognostic factors. Results: From a total of 76 patients with SBA received surgical resection, 56 were selected in this study who underwent curative resection with histological confirmation and did not receive adjuvant chemotherapy. The median age was 64 years (range: 20-85). Thirty-five patients (61%) were male. Forty-five patients (80%) had tumors in duodenum, 6 (11%) in jejunum and 5 (9%) in ileum. Pathological T stage were pT1a/T1b/T2/T3/T4 in 9/2/4/14/27 patients, and pathological N stage (pN) were pN0/N1/N2 in 29/16/11. The 1/3/5-year OS in all patients were 92.5/77.5/71.6%, and 1/3/5-year RFS were 76.5/68.9/61.6%. The 5-year RFS of pN0 (stage I/IIA/IIB) / N1 (stage IIIA) /N2 (stage IIIB) were 81.2/51.6/20.8%, and 5-year OS were 88.2/71.6/26.7%, respectively. Univariate analysis demonstrated that pN, presence of lymphatic and venous invasion were associated with poor OS. In multivariate analysis, pN was a significant predictor of poor OS (HR: 5.39 [N0 vs N1], 21.74 [N0 vs N2], 4.03 [N1 vs N2], p = 0.042). These findings were also seen in RFS. Conclusions: This study showed survival outcome of curatively resected SBA was better compared with previous reports, and pN was a significant prognostic factor of RFS and OS.
Radiotherapy for intrahepatic cholangiocarcinoma: An analysis of the National Cancer Database.
Authors: Hammad Abdulrahman Y , Younan George , Rajeev Rahul , Berger Nicholas Gerard , Turaga Kiran , Johnston Fabian McCartney , Christians Kathleen K. , Gamblin T. Clark 
Published: February 2017

379 Background: The role of radiotherapy (RT) for surgically resected intrahepatic cholangiocarcinoma (ICC) remains poorly defined. Radiotherapy is often considered when a positive resection margin exists. The present study sought to examine the impact of radiotherapy following liver resection. Methods: Patients with early stage ICC, who underwent surgical resection, were identified from the National Cancer Database (1998-2011). Patients were stratified by resection margin status and receipt of RT. Survival was analyzed by Kaplan-Meier method and a multivariate regression model was used to identify predictors of survival. Results: A total of 2,182 patients were identified. R0 status was obtained in 1,624 patients (74.4%). RT was delivered to 405 patients (R0=209, R1/R2=196). In the R1/R2 group, 196 patients received RT vs. 362 R1/R2 patients that did not receive RT. Survival for R0 vs. R1/R2 was 32m vs. 16.5m (p<0.001). RT appeared to trend toward improving survival for R1/R2 patients, though this was not significant (20.4m vs. 14.5m, p=0.191). In a multivariate model accounting for age, sex, comorbidities, disease stage and resection margins, RT was not a predictor of survival. Negative predictors of survival included age>65years (Hazards Ratio [HR]: 1.20 (95%CI: 1.04-1.39), p=0.013), and positive resection margins (HR: 1.95 (95%CI: 1.65-2.30), p<0.001). Female sex was the only positive predictor of survival identified (HR: 0.76 (95%CI: 0.65 -0.88), p<0.001). Conclusions: Surgical resection with negative margins provides the best outcome for patients with ICC. Radiotherapy does not appear to significantly impact survival in patients with positive resection margins.