bluuebunny/crossref_metadata_2025_split huggingface dataset:
Next Generation Sequencing (NGS) to reveal mutations in IDH1 and its effect on patient (pt) outcomes in advanced biliary tract cancer (aBTC) who received gemcitabine and cisplatin (GC).
Authors: Ahn Daniel H. , Ahn Chul , Jain Apurva , Mikhail Sameh , Wu Christina Sing-Ying , Goldberg Richard M. , Ciombor Kristen Keon , Noonan Anne M. , Sadavartia Priyanka , Shroff Rachna T. , Javle Milind M. , Chen James Lin , Bekaii-Saab Tanios S. 
Published: February 2017

287 Background: aBTC is uncommon and has a dismal prognosis with limited therapeutic options. First-line therapy for untreated aBTC is GC, with no approved therapies in the refractory setting. To assess for tumor-specific genetic variants that affect outcomes in patients (pts) who received GC in aBTC, we performed NGS in pts treated with who received GC as first-line therapy. Methods: Archival formalin-fixed, paraffin-embedded samples from pts with mBTC from Ohio State University and MD Anderson Cancer Center who received GC in the first-line and underwent NGS as part of routine care. 315 cancer-related genes plus select introns from 28 genes altered in solid tumors were included in the NGS panel. Univariate Cox regression model was used to determine the association between gene mutations with progression free survival (PFS) and (OS). Results: 80 evaluable pts with aBTC treated with first-line GC chemotherapy underwent successful genomic profiling. A total of 414 cancer-specific mutations were identified, where 49 (12%) genes had mutations with > 5% frequency. 17 of the 49 were known mutations. From the comprehensive analysis, somatic mutations in IDH1 (11 of 80 pts; 13%) (HR 0.31; p = 0.035) was associated with improved overall survival (OS) and progression free survival (PFS). Pts wild type for IDH1 had a median OS of 17.7 months and PFS of 4.5 months, while those with an IDH1 mutation had a median OS that was not reached and an improved PFS of 5.7 months. Conclusions: Somatic mutations in IDH1 were associated with improved clinical outcomes in pts with aBTC who received GC as first-line therapy which is consistent with other solid tumor malignancies. IDH1 is a therapeutic target of interest, where future prospective studies will be necessary to validate the predictive utility and its relevance in pt outcomes in aBTC.
Intra and extrahepatic cholangiocarcinoma: An evaluation of adjuvant therapy.
Authors: Wiisanen Jeff , Hubbard Joleen Marie , Bergquist John , Alberts Steven R. , Nagorney David , Truty Mark Joseph 
Published: February 2017

291 Background: Cholangiocarcinoma (CCA) is a rare malignancy with poor survival. The only curative therapy is resection and the role of adjuvant therapy is not well defined. Despite the unproven benefit, adjuvant therapy is used in resected CCA. The aim of this study is to analyze our institution’s outcomes for peri-operative treatment of resected intrahepatic and extrahepatic CCA. Methods: We retrospectively analyzed 145 intrahepatic (iCCA) and 109 extrahepatic (eCCA) CCA patients who underwent resection at the Mayo Clinic, Rochester. The majority of treated patients received adjuvant chemotherapy; however neo-adjuvant and radiation were also included. Results: In stage 1-2 iCCA patients, the HR indicated worse outcomes for time to recurrence and death. For stage 3-4 or node positive disease, outcomes were not significantly different. Those with node unknown/negative disease had significantly worse time to recurrence but not OS. There was a significant difference in stage and treatment modality between these groups (see table). Among eCCA, for any stage and node positive disease, outcomes were not different. In the node unknown/negative group, neither time to recurrence nor OS differed significantly. In controlling for different features in multi-variable analyses, no significant differences were observed (see table). Conclusions: This retrospective study does not show a significant difference in recurrence free or OS for treated patients. The apparent lack of benefit most likely reflects selection bias among treatment groups. Prospective, randomized trials are needed to make sound recommendations in adjuvant treatment for CCA. [Table: see text] [Table: see text]
Did multiagent chemotherapy improve clinical outcomes of advanced pancreatic cancer? A single center experience of 408 cases.
Authors: Nakai Yousuke , Isayama Hiroyuki , Ishigaki Kazunaga , Takahara Naminatsu , Hamada Tsuyoshi , Mizuno Suguru , Kogure Hirofumi , Matsubara Saburo , Yamamoto Natsuyo , Tada Minoru , Koike Kazuhiko 
Published: February 2017

293 Background: We previously reported the introduction of S-1 improved overall survival (OS) in advanced pancreatic cancer (PC), but in a pooled analysis of 3 RCTs, a combination of gemcitabine and S-1 (GS) improved OS in locally advanced PC (LAPC), but not in metastatic PC (MPC), compared to gemcitabine (Gem) alone. More recently, FOLFIRINOX, a multiagent chemotherapy, is shown to improve OS in MPC. We conducted clinical trials of a combination of Gem, S-1 and leucovorin (GSL) to further enhance antitumor effects. Herein, we retrospectively studied whether these multiagent regimens, GSL & FOLFIRINOX, affected the prognosis of APC, especially MPC. Methods: A total of 408 pts with APC receiving chemotherapy were grouped by treatment era into 3 groups: Group 1 (Years 2001-5: 53 pts prior to S-1 introduction), Group 2(Years 2005-11: 240 pts post S-1 introduction) and Group 3 (2012-14: 115 pts post multiagent treatment introduction), and clinical outcomes were compared. Results: Patient characteristics and protocol are shown in Table 1. Treatment protocol was single in 233, dual 142, and multiagent in 33. Response rate & disease control rate in Groups 1/2/3 were 2/8/17% & 26/67/73%. In LAPC, PFS was 6.2/8.9/7.9 & OS was 13.4/17.2/19.7 months in Groups 1/2/3. Meanwhile, in MPC, PFS was 2.0/3.5/4.8 & OS was 6.7/8.6/9.6 months in Groups 1/2/3. When treatment protocols were compared, in LAPC, PFS & OS were 7.0/11.7/8.8 & 13.6/22.6/22.6 months in singe/dual/multiagent chemotherapy. In MPC, PFS & OS were 3.1/3.5/6.0 & 8.3/8.1/13.7 months in single/dual/multiagent chemotherapy. Conclusions: While the introduction of S-1 led to longer OS in LAPC, recent introduction of multiagent chemotherapy appeared to improve OS in MPC. Whether multiagent chemotherapy would lead to longer OS than dual chemotherapy in LAPC needs further investigation. Table 1. [Table: see text]
Effect of ablative radiotherapy on survival in patients with inoperable intrahepatic cholangiocarcinoma: A dose response analysis.
Authors: Crane Christopher H. , Tao Randa , Bhosale Priya , Javle Milind M. , Shroff Rachna T. , Aloia Thomas A. , Kaseb Ahmed Omar , Koay Eugene Jon , Bishop Andrew Justin , Swanick Cameron Williams , Hong Theodore S. , Das Prajnan , Krishnan Sunil 
Published: February 2017

294 Background: Advances in radiotherapy (RT) techniques and image guidance (IGRT) have enabled ablative doses to be delivered to large liver tumors. We evaluated the effects of RT dose escalation in the treatment of intrahepatic cholangiocarcinoma (IHCC). Methods: 79 consecutive patients with inoperable IHCC were treated between 2002–2014. Median tumor size 7.9 cm (range 2.2–17 cm), 57% had nodes+ and 20% had metastatic disease. 89% received gemcitabine and cisplatin before RT (35–100 Gy, median 58.05 Gy) for a median biologic equivalent dose (BED) of 80.5 Gy (range 43.75–180 Gy). 57% were treated with concurrent capecitabine. CT on rails IGRT with gating were used to deliver higher doses. Results: Median FU was 33 months (range 11–93 ). Median overall survival rate (OS) after diagnosis was 30 months; 1, 2, and 3-year OS rates were 87%, 61%, 44%. The median duration of local tumor control (LC) was 23 months; 1, 2, and 3-year LC rates were 81%, 45% and 27%. RT dose was the most important prognostic factor. Higher doses correlated with improved LC and OS. The 3-year OS for a BED greater than 80.5 was 73% versus 38% for those receiving lower doses (P =0.017). Similarly, 3-year LC was significantly higher (78% versus 45%, P= 0.04). On multivariate analysis, RT dose was significant for LC (P= 0.004) and OS (P= 0.006). The majority of patients (32/36, 89%) whose cause of death could be determined died from liver failure related to intrahepatic disease progression. Only 4 patients (11%) died from distant metastatic disease. There were no significant treatment related toxicities. Conclusions: Higher doses of RT improve LC and OS in inoperable IHCC. A BED > 80.5 Gy appears to be ablative for large IHCCs. Long term survival rates compare favorably to resection. RT schedules that achieve a BED > 80.5, such as 67.5 Gy in 15 fractions and 75 Gy in 25 fractions, should be used. Solutions for internal organ motion and IGRT are necessary for safe delivery of high doses near bowel. These findings support the use of 67.5 Gy in 15 fractions (BED = 97.88 Gy) in the current phase III NRG-GI001 randomized trial evaluating whether the addition of RT to chemotherapy affects survival for inoperable IHCC patients.
Clinicopathological features and response to platinum-based chemotherapy in pancreatic neuroendocrine carcinoma: A retrospective multicenter study of 70 patients.
Authors: Hijioka Susumu , Hosoda Waki , Matsuo Keitaro , Ueno Makoto , Furukawa Masayuki , Yoshitomi Hideyuki , Kobayashi Noritoshi , Ikeda Masafumi , Ito Tetsuhide , Nakamori Shoji , Ishii Hiroshi , Kodama Yuzo , Morizane Chigusa , Yanagimoto Hiroaki , Yane Kei , Notohara Kenji , Furuse Junji , Yatabe Yasushi , Mizuno Nobumasa ,   Japan pNEC Study Group
Published: February 2017

298 Background: The WHO classified pancreatic neuroendocrine Neoplasms (pNEN) in 2010 as G1, G2, and neuroendocrine carcinoma (NEC). However, pNEC is suspected to include heterogeneous disease entities, but is still not fully studied. We aimed to clarify the clinicopathological and molecular characteristics of NECs. Methods: A total of 100 cases clinical data and pathological slides originally diagnosed as NEC by the WHO in 2010(WHO-NEC) were retrospectively collected from 31 institutes. Expert pathologists were reassessed all cases slide using the designed protocol and reclassified as well differentiated NET (NET-G3), small cell NEC(SCNEC), and large cell NEC(LCNEC) by morphological features. Results: Thirty cases were eliminated mostly because acinar cell carcinoma, NET-G2 and malignant tumor not otherwise specified. Remaining 70 cases were subclassified into 21(30%) NET-G3, 31 (44.3%) SCNEC, 18(25.7%) LCNEC. Comparisons of NET-G3 vs. SCNEC vs. LCNEC revealed the following traits: ENETS stageⅣ: 76%, 81% and 78%; median Ki67 LI: 28.5% (15-53), 85 % (50-100) and 70.0 %(22-90); abnormal Rb expression: 0 %, 59% and 47%; KRAS mutations: 0 %, 48% and 50%; response rates to platinum-based chemotherapy: 0%, 60% and 44.4% ;and median survival(days): 1255, 340 and 196, respectively. When KRAS divided wild (n = 20) and KRAS mutation group (n = 42), response rate to platinum-based chemotherapy was 77% vs 23%.In the same manner, when Rb immune stain divided negative (n = 24) and positive (N = 41), response rate to platinum-based chemotherapy was 80% vs 23.8%. Besides response rate to platinum-based chemotherapy of KRAS mutation(+) and Rb immunopositivity(-) group (n = 7) were 100%, on the other hand, KRAS mutation(-) and Rb immunopositivity(+) group (n = 7) were 18.7%. Conclusions: In this retrospective study, WHO-NEC include 30% NET-G3. NET-G3 are genetically different from SCNEC and LCNEC. As for chemotherapy,Mutated KRAS and/or Rb immunonegativity in tumors with pNEC is associated with response to platinum-based chemotherapy.
Aggressive surgery for advanced colorectal liver metastases in the era of multidisciplinary approaches.
Authors: Mise Yoshihiro , Inoue Yosuke , Ishizawa Takeaki , Takahashi Yu , Saiura Akio 
Published: February 2017

299 Background: The number of colorectal liver metastases (CLM) is accepted as a strong predictor of survival after surgery. However, recent advances in multidisciplinary approaches have dramatically changed surgical outcomes of CLM. Clinical implications of aggressive surgery for advanced CLM need to be reviewed in relation to the trend in treatment strategies. Methods: We reviewed 581 patients who underwent curative hepatectomy for CLM from 1999 to 2012. One hundred and eighty-nine patients underwent surgery for advanced CLM (n ≥ 4) and were classified according to year of surgery (first: 1999–2003 [n = 30]; second: 2004–2008 [n = 82]; and third: 2009–2012 [n= 77]). The frequency of perioperative chemotherapy for CLM, preoperative gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI), and contrast-enhanced intraoperative ultrasonography (CE-IOUS), and long-term outcomes were compared among the three periods. Results: The frequency of perioperative chemotherapy, EOB-MRI, and CE-IOUS increased with time (P <.001). The 3-/5-year overall survival in the third period (58.7/51.8%) was similar to that in the second period (59.8/43.9%, P =.828) and that of 72 patients who had 1–3 CLM in the first period (70.8/51.0%, P =.991). Advanced CLM was an independent factor in the first (P =.001, hazard ratio: 2.91) and second (P=.040, hazard ratio: 1.56) periods. However, multivariate analysis revealed that advanced CLM was not a predictive factor of overall survival in the third period. Conclusions: The prognostic impact of advanced CLM diminished owing to evolution in multidisciplinary treatment. Aggressive surgery for advanced CLM offers favorable prognosis similar to that of patients with few CLM in the early period.
The role of adjuvant therapy after R0 resection for patients with intrahepatic and perihilar cholangiocarcinoma.
Authors: Kim Young Saing , Park Inkeun , Oh Sung Yong , Go Se-Il , Kang Jung Hun , Song Haa-na , Park Joon Oh , Ji Jun Ho , Hwang In Gyu , Jang JoungSoon 
Published: February 2017

302 Background: There is still debated regarding the optimal treatment strategy in cholangiocarcinoma (CC) after curative resection. The aim of this study was to analyze the role of adjuvant therapy in R0-resected intrahepatic and perihilar CC. Methods: We retrospectively reviewed the medical records of patients who underwent R0 resection for intrahepatic and perihilar CC between January 2001 and December 2013 at six cancer centers. Adjuvant therapy consisted of chemotherapy (CT), chemoradiotherapy (CRT), or radiotherapy (RT). The outcomes of our study were recurrence-free survival (RFS) and overall survival (OS). Multivariable Cox proportional hazards model was used to identify prognostic factors for survival. Results: A total of 137 patients were included in the analysis; 58.4% of patients had intrahepatic CC and 25.5% had lymph node involvement. Seventy-three patients (53.3%) received adjuvant therapy (CT/CRT/RT: 48/13/12, respectively). A greater percentage of patients receiving adjuvant therapy had stage III-IVA (P = 0.010), high histologic grade (P = 0.035), and positive lymph nodes (P = 0.088). Multivariable analysis identified positive nodes (hazard ratio (HR), 3.60; P < 0.001), poor tumor differentiation (HR, 2.35, P = 0.048), and high baseline CA 19-9 level (HR, 1.97; P = 0.013) as predictors of decreased OS. The effect of adjuvant therapy varied according to the treatment modality. Adjuvant CRT was significantly associated with longer RFS (HR, 0.44; P = 0.036) but OS benefit was non-significant HR, 0.56; P = 0.245). In node-positive patients, CRT had a trend for longer OS (HR, 0.24; P = 0.097). In contrast, CT did not improve RFS (HR, 1.13; P = 0.617) or OS (HR, 1.70; P = 0.114). RT alone was associated shorter RFS (HR 3.08; P = 0.009) and OS (HR, 6.86, P < 0.001). Conclusions: Adjuvant CT and RT were not associated with a survival advantage in R0-resected intrahepatic and perihilar CC. CRT appears to be appropriate treatment after complete resection especially in lymph node-positive patients.
Randomized clinical trial of the effect of simo decoction plus acupuncture and chewing gum on postoperative ileus in patients with hepatocellular carcinoma after hepatic resection.
Authors: Zhong Jian-Hong , You Xue-Mei , Ma Liang , Li Le-Qun 
Published: February 2017

307 Background: Postoperative ileus (POI) is a common complication following hepatic resection that delays recovery of bowel function and increases length of hospital stay. Simo decoction (SMD) and acupuncture tsusanli acupoint are used to enhance bowel hypomotility in China. Chewing gum reducing POI is reported. The aim of study is to evaluate the effect of SMD plus acupuncture tsusanli acupoint and chewing gum alone on POI and length of hospital stay in patients with hepatocellular carcinoma (HCC) after hepatic resection. Methods: Primary HCC patients undergoing hepatic resection were randomized to SMD plus acupuncture, chewing gum, or empty control group. Interventions were started on postoperative day 1 for six consecutive days or until flatus. Primary endpoints were POI and length of hospital stay. Secondary endpoints were surgical complications. Results: Between March 2015 and August 2015, 162 patients were randomized to SMD plus acupuncture (55), chewing gum (53), or empty control (54). SMD plus acupuncture or chewing gum group have significantly shorter first peristalsis, flatus, and defaecation time than empty control group (all P< 0.05). The mean (s.d.) length of hospital stay of the three groups was 14.0 (4.9), 14.7 (6.2), and 16.5 (6.8) days. The difference between SMD plus acupuncture and empty control group was significant (P = 0.014). However, chewing gum cannot significantly shorten hospital stay than empty control (P = 0.147). Interventions groups had less grade I and II complications. Conclusions: SMD plus acupuncture or chewing gum is a safe treatment to reduce POI and shorten hospital stay. Registration number: NCT02438436 (https://clinicaltrials.gov). Clinical trial information: NCT02438436.
Efficacy of chemotherapy in patients with pancreatic acinar cell carcinoma.
Authors: Yoo Changhoon , Kim Bumjun , Kim Kyu-Pyo , Lee Jae-Lyun , Kim Tae Won , Ryoo Baek-Yeol , Chang Heung-Moon 
Published: February 2017

308 Background: Pancreatic acinar cell carcinoma (ACC) is a rare cancer of the exocrine pancreas. Because of its rare incidence, efficacy of chemotherapy in this patient population still remains largely unknown. Therefore, we retrospectively analyzed the outcomes of patients with pancreatic ACC who received chemotherapy. Methods: Between January 1997 and March 2015, a total of 22 patients with histologically confirmed locally advanced unresectable or metastatic pancreatic ACC were identified in Asan Medical Center, Seoul, Korea. Among them, 15 patients received chemotherapy and 2 patients with locally advanced disease underwent concurrent chemoradiotherapy followed by chemotherapy; these 17 patients were included in this analysis. Results: Median age was 58 year old (range, 29-72), and 15 patients (88%) were male. Mixed acinar-neuroendocrine tumor and mixed acinar-adenocarcinoma was found in 1 (6%) and 2 (12%) patients, respectively. The most common metastatic site was liver (n = 9, 53%), followed by intraabdominal lymph nodes (n = 5, 29%), and peritoneum (n = 3, 18%). As 1st-line therapy, 5-FU or its derivative were given in 7 patients (41%), gemcitabine in 6 (35%), gemcitabine plus capecitabine in 2 (12%) and FOLFOX in 2 (12%). Objective response rate (ORR) was 30% and median time-to-progression (TTP) was 5.8 months (95% CI, 2.9-8.6). After progression, 2nd-line chemotherapy was given in 9 patients; 5 and 4 patients received FOLFOX and gemcitabine, respectively. On 2nd-line chemotherapy, ORR was 44% and median TTP was 6.3 months (95% CI, 0.3-12.4); patients with FOLFOX had significantly better TTP compared to those with gemcitabine (median 6.5 vs 1.4 months, p = 0.003). The ratio of TTP at 1st-line chemotherapy to TTP at 2nd-line chemotherapy was significantly higher in patients with FOLFOX (2.10 [range, 0.16-8.30] compared to those with gemcitabine (0.12 [0.08-0.25]; p = 0.03). Median overall survival in all patients was 16.9 months (95% CI, 14.4-19.4). Conclusions: Pancreatic ACC seems to have better prognosis compared to pancreatic adenocarcinoma. Our results suggest that oxaliplatin-containing regimen may have improved activity against pancreatic ACC.
Peri-operative modified FOLFIRINOX (mFOLFIRINOX) in resectable pancreatic cancer (PDAC): A pilot study.
Authors: Marsh Robert de Wilton , Baker Marshall , Catenacci Daniel V.T. , Kozloff Mark , Polite Blase N. , Posner Mitchell C. , Roggin Kevin K. , Talamonti Mark S. , Kindler Hedy Lee 
Published: February 2017

312 Background: Surgical resection plus adjuvant gemcitabine or 5-FU is standard therapy for resectable PDAC. Infusional 5-FU, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) has substantial activity in metastatic PDAC. Efficacy and tolerability of peri-operative FOLFIRINOX in resectable PDAC is unknown. Methods: Patients (pts) with ECOG PS 0/1 and resectable PDAC confirmed by multidisciplinary review received 4 cycles of mFOLFIRINOX (mFFX)(oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2 day 1, 5-FU 2400 mg/m2 x 48 hours, peg-filgrastim 6 mg SQ day 3) pre- and 4 cycles post- surgery. Results: 21/21 enrolled pts started therapy (median age: 63 (47-78), 81% ECOG 0). 20/21 pts completed 4 cycles of preoperative mFFX (1 withdrew for toxicity), 17/21 pts had successful surgical resection (3 had disease noted in the liver at surgery) and 14/21 completed 4 cycles of postoperative mFFX (2 pts expired prior to postoperative mFFX within 90 days of surgery -1 from an M.I. and 1 from a GI bleed; 1 pt had excessive toxicity after cycle 5). Radiographic response by RECIST following preoperative therapy was 1 CR, 3 PR, 16 SD, 0 PD. Of the 17 (81%) patients undergoing curative-intent surgery, 16/17 (94%) had R0 resections. Treatment effect was seen in 10/17 specimens with 1 pathologic CR. Doses were modified per protocol in 30% pts preoperatively (neuropathy 1; thrombocytopenia 2; neutropenia 3; diarrhea 2) and 26% postoperatively (neuropathy 3; diarrhea 3; allergic reaction 1). Grade III and IV adverse events were observed in 23% and 14% pts (overlapping) in the preoperative, and 26% and 0.06% pts in the postoperative phases. 18 pts are alive with a median follow up of 17.3 months. Conclusions: 17/21 (81%) pts completed neoadjuvant mFFX and surgical resection. 14/21 (66%) pts completed all planned therapy. Radiographic responses were rare but efficacy is suggested by the high R0 resection rate: 16/17 (94%) in pts undergoing resection, and 16/21 (76%) pts overall. Toxicity was manageable and within the expected range. 8 cycles of mFFX is a feasible and tolerable peri-operative regimen in pts with resectable PDAC and ECOG PS 0/1. Definitive assessment of efficacy will require longer follow up and larger studies. Clinical trial information: NCT01660711.