bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet-to-hemoglobin ratio to predict progression-free survival for patients with locally advanced hepatocellular carcinoma.
Authors: Li Xing , Xing Yan-Fang , Lin Zhi-Huan , Hong Ying-fen , Wu Dong-hao , Wang Tian-tian , Ma Xiao-kun , Huang Mingsheng , Dong Min , Lin Qu , Wu Xiang-yuan
Published: March 2017

463

Background: The prognosis of locally advanced hepatocellular carcinoma (HCC) patients is far from being identified which makes the treatment decision controversial. The present study aimed to assess role of blood cell counts, routine liver function tests in predicting the progression-free survival (PFS) of these patients. Methods: A total of 243 HCC patients staged Barcelona Clinic Liver Cancer (BCLC) B or C were analyzed retrospectively. The current staging systems of HCC were investigated about their performance on predicting PFS. And then, the novel prognostic factors were evaluated by integrating in to the best staging systems which was used to determine their independent prognostic value. Results: Cancer of the liver Italian program (CLIP) score system and advanced liver cancer prognostic system (ALCPS) stages were indentified to be testing systems with best akaike information criterion (AIC) index and linear trend χ2 among all the current 12 staging systems for this patient subgroup. Then, the prognostic value of novel parameters was assessed by integration into CLIP and ALCPS score systems. Platelet-to-Hemoglobin Ratio (PHR) were confirmed to an independent predictor for PFS of locally advanced HCC patients when integrated into CLIP and ALCPS score systems ( p= 0.026 and 0.009, respectively) with the other parameters, including platelet and hemoglobin, failed to reach statistical significance. Moreover, PHR improved the performance of CLIP and ALCPS score systems by adjusted into it, which improved their discriminatory ability. Furthermore, PHR were designated ≤ 1.26 as low level and > 1.26 as high level, according to which HCC patients were dichotomized into two groups. Locally advanced HCC patients with low PHR presented better 1 year disease progress rate (24.0% vs 41%) and overall survival (62.5% vs 38.8%) compared with patients with high PHR level. Besides, PHR level was associated with prognostic factors such as international normalized ratio, presence of ascites, serum albumin, serum α-fetoprotein, total bilirubin and portal vein thrombosis. Conclusions: The present study firstly indentified PHR as an independent prognostic factor in locally advanced HCC patients.
Modified FOLFIRINOX for metastatic pancreatic adenocarcinoma after failure of nab-paclitaxel plus gemcitabine.
Authors: Ozaka Masato , Sasaki Takashi , Kataoka Seita , Kanata Ryo , Ishigaki Kazunaga , Yamada Ikuhiro , Matsuyama Masato , Takano Koichi , Sasahira Naoki
Published: March 2017

467

Background: Both FOLFIRINOX and Nab-paclitaxel plus Gemcitabine standard treatment in first-line treatment of metastatic pancreatic adenocarcinoma (MPA). It could be of interest to use them consecutively, knowing that there is currently no standard for 2nd line treatments for MPA. The aim of this study was to evaluate the efficacy and tolerability of modified FOLFIRINOX after gemcitabine plus Nab-paclitaxel failure in MPA. Methods: From January 2015 to March 2016, medical records were retrospectively reviewed for consecutive patients receiving modified FOLFIRINOX for a histologically proven MPA after failure of Nab-paclitaxel plus Gemcitabine. Patients were treated with modified FOLFIRINOX every 2 weeks as follows: intravenous oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, 5-FU infusion 2,400 mg/m2 over 46 h, no bolus 5-FU, until disease progression, patient refusal or unacceptable toxicity. Results: Modified FOLFIRINOX was administered to 23 pts. Among these patients, median age was 64 years (range 42.4 - 74.2). 83% of the patients had a PS 0, the primary site of the tumor was the head of the pancreas in 39% of patients, and 26% of patients experienced recurrence after resection. Disease control rate was 66.7% (n = 17) with a 23.8 % (n = 17) objective response rate (RECIST). Within the whole cohort, median PFS was 4.3 months (95% CI: 3.1-5.3) and median overall survival (OS) was 9.3 months (95% CI: 3.8-14.8). Since the start date of first line chemotherapy with Nab-paclitaxel plus Gemcitabine, median OS was 18.8 months (95% CI: 9.6-27.9). No toxic death occured. Grade 3-4 toxicities were reported in 30% of patients and were neutropenia (17%), anemia (8%), cholangitis (8%) and acute kidney injury (4%). Conclusions: Modified FOLFIRINOX seems promising with a manageable toxicity profile after Nab-paclitaxel plus Gemcitabine failure, in selected patients able to receive second line treatment for a MPA. These promising results have now to be confirmed in a phase III randomized trial.
The short- and long-term outcomes of pancreatic resection for pancreatic adenocarcinoma in patients older than 75 years.
Authors: Kazama Keisuke , Aoyama Toru , Atsumi Yosuke , Murakawa Masaaki , Shiozawa Manabu , Kobayashi Satoshi , Ueno Makoto , Morimoto Manabu , Yukawa Norio , Oshima Takashi , Yoshikawa Takaki , Rino Yasushi , Masuda Munetaka , Morinaga Soichiro
Published: March 2017

470

Background: The short- and long-term outcomes of pancreatic resection for pancreatic adenocarcinoma have not been evaluated in elderly patients. Methods: This retrospective study selected patients who underwent curative surgery for pancreatic cancer at our institution. Patients were categorized into two groups; non-elderly patients(age <75 years: group A) and non-elderly patients (age ≥75 years: group B). The surgical morbidity, motality, overall survival (OS), and recurrence-free survival (RFS) rates in the two groups were compared. Results: A total of 221 patients were evaluated in the study. The overall complication rates are 44.8% in Group A and 52.6% in Group B. Surgical mortality was observed in 2 patients due to an abdominal abcess and cardiovascular disease in Group A (1.1%) and in 1 patient due to postoperative bleeding in Group B (2.6%). There were no significant differences (p=0.379 and p=0.456, respectively). Furthermore, the 5-year OS and RFS rates were similar between the elderly patients and non-elderly patients (18.55% vs. 20.2%, p=0.946 and 13.1% vs. 16.0%, p=0.829 respectively). Conclusions: The short-term outcomes and long-term outcomes survival after pancreatic resection for pancreatic adenocarcinoma were almost equal in the elderly and the non-elderly patients in this study. Therefore, it is unnecessary to avoid pancreatic resection for pancreatic adenocarcinoma in elderly patients simply because of their age.
An open-label, single-group, multicenter phase II study of lanreotide autogel (LAN) in Japanese patients (pts) with neuroendocrine tumors (NET).
Authors: Ito Tetsuhide , Hisamatsu Seiichi , Nakajima Akihiro , Shimatsu Akira
Published: March 2017

471

Background: LAN is a long-acting somatostatin analog indicated in EU for the treatment of carcinoid syndrome and in the US and EU as antiproliferative treatment in pts with gastroenteropancreatic (GEP) -NET. The antitumor efficacy of LAN in pts with GEP-NET was evaluated in the phase III CLARINET study. No study to date has reported the antitumor effects of somatostatin analog in Japanese pts with NET. Methods: In this open-label, single-arm study, Japanese pts with Grade 1 or 2 unresectable metastatic or locally advanced NET received 120 mg once every 4 weeks for 48 weeks. Pts who completed the study were subsequently enrolled in the long-term extension study. The primary endpoint was the clinical benefit rate (CBR: the ratio of pts with a complete response, a partial response (PR), or stable disease over 24 weeks). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) (RECIST 1.1, central review), serum chromogranin A (CgA) level and quality of life using the EORTC QLQ-C30. The results of the CLARINET study cohort were compared with those from a matched population. Results: 32 pts were recruited in 10 sites. Mean age was 61.7 years. 67.9% were male. The primary tumor sites were pancreas (n = 14), foregut (2), midgut (2), hindgut (8), and unknown (6). Four pts had gastrinoma, and 3 of them had multiple endocrine neoplasia type 1. In the Full Analysis Set (n = 28), 39.3% of pts had progressive disease at baseline according to RECIST criteria. The CBR at 24 weeks was 64.3% (18 of 28 pts) and the median PFS was 36.3 weeks. A PR was confirmed in 1 patient during the 60 weeks of the extension study (ORR: 3.6%). For PFS, the subgroup analysis showed that the results of pts with no progressive disease at baseline or prior treatments for NET were similar to the results of pts in the CLARINET study. LAN decreased serum CgA by at least 50% in 15 of 17 pts (88.2%) who had elevated CgA levels at baseline. Frequent adverse reactions included injection site induration (28.1%), pale stools (18.8%), flatulence (12.5%), and diabetes (12.5%). Conclusions: The efficacy and safety of LAN in this study clearly show that LAN will be a useful treatment option for Japanese pts with NET. Clinical trial information: 132375,142698.
The efficacy of first-line chemotherapy in recurrent pancreatic cancer after S-1 adjuvant chemotherapy.
Authors: Kanata Ryo , Ozaka Masato , Kataoka Seita , Ishigaki Kazunaga , Yamada Ikuhiro , Sasaki Takashi , Matsuyama Masato , Takano Kouichi , Sasahira Naoki
Published: March 2017

475

Background: In Japan, adjuvant chemotherapy with S-1 for 6 months is standard care for resected pancreatic cancer. However, the efficacy of chemotherapy for recurrent pancreatic cancer(RPC) after adjuvant S-1 chemotherapy is not well evaluated. Methods: Medical records were retrospectively reviewed for consecutive patients who had RPC after adjuvant S-1 treatment and received chemotherapy between April 2013 and July 2016. Recurrence free interval (RFI) was defined as the interval from adjuvant S-1 initiation to cancer recurrence. Overall survival (OS) and progression free survival (PFS) after 1st line chemotherapy for RPC were compared between patients with RFIs of shorter than 6 month (Group S) and longer than 6 months (Group L). Results: In the 53 patients evaluated, the median duration of adjuvant S-1 chemotherapy was 5.1 months, and the median RFI was 8.3 months. After recurrence, they received Gemcitabine alone (20 patients), Gemcitabine+nab-paclitaxel (28 patients), modified FOLFIRINOX (one patient), and other regimen (4 patients). In all patients, the median PFS was 7.3 months and the median OS was 14.8 months. When compered in two groups (group S and group L), median OS in group S and group L was 6.7 months (95% confidence interval(CI): 4.2-12.9) and NA (95% CI: 13 months-NA) , respectively (p < 0.001), and median PFS was 3.8 months (95%CI: 2.5-9.1) and 7.3 months (95%CI: 3.9-15.3), respectively (p = 0.11). Multivariate Cox regression analysis revealed CEA < 4.0 mg/dl before chemotherapy and an RFI of ≥ 6 months were significantly associated with longer survival. Conclusions: These data suggest that RFI < 6 months is a surrogate marker for a poor prognosis in patients with RPC.
A phase II study of gemcitabine, erlotinib, and S-1 in patients with advanced pancreatic cancer.
Authors: Han Boram , Kim Hyeong Su , Choi Dae Ro , Shim Byoungyong , Lee Kyung Hee , Kim Jin Won , Kim Jung Han , Kim Jung Hoon , Song Hunho , Park Choong Kee , Moon Sung Hoon , Kim Jong Hyeok , Jeon Jang Yong , Lee Jung Woo , Zang Dae Young
Published: March 2017

476

Background: Gemcitabine-based chemotherapy is considered as a standard front-line treatment for patients with advanced pancreatic cancer. Although addition of erlotinib or S-1 to gemcitabine has yielded better outcomes, it has showed just modest improvement in survival. To overcome this limitation, we evaluated the efficacy and safety of the combination of gemcitabine, erlotinib, and S-1 for the treatment of advanced pancreatic cancer. Methods: Chemotherapy-naïve patients with pathologically proven locally advanced, recurrent or metastatic pancreatic adenocarcinoma were assessed for eligibility. Gemcitabine at 1,000 mg/m2 was administered intravenously on day 1, and 8, erlotinib at 100 mg/day was administered on day 1-21, and S-1 at 60 mg/m2 was administered on days 1-14 every 21 days and continued to maximum of 8 cycles of treatment. Dose escalation of S-1 to 80 mg/m2 was permitted from second cycle for pre-defined tolerable patients. Results: Thirty-seven patients (median age 61.5 years) were enrolled. A total of 140 cycles of chemotherapy were administered (median of 3.8; range 1–8 cycles). Toxicities were evaluated in 36 patients, and the responses were evaluated in 31 patients. Major grade 3/4 toxicities included neutropenia (25%), febrile neutropenia (2.8%), fatigue (22.2%), infection (8.3%), vomiting (5.6%), and mucositis (5.6%). The overall response rate was 12.9% [95% confidence interval (CI), 5.1-28.9%] and disease control rate was 74.2% (95% CI, 56.8-86.3%). The median progression-free survival and overall survival were 3.4 months (95 % CI, 2.3-4.5 months) and 5.7 months (95 % CI, 3.9-7.6 months), respectively. Conclusions: The combination of gemcitabine, erlotinib, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced pancreatic cancer. Clinical trial information: NCT01693419.
Clinical outcomes of FOLFIRINOX in locally advanced pancreatic cancer: A single center experience.
Authors: Lee Jongchan , Lee Jong-Chan , Kim Hyoung Woo , Kim Jaihwan , Hwang Jin-Hyeok
Published: March 2017

480

Background: Approximately, one third of pancreatic cancer patients have locally advanced status at diagnosis. Systemic chemotherapy or chemoradiotherapy is the main option for patients with locally advanced pancreatic cancer (LAPC). Recently, many studies have been investigating the efficacy of FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan and leucovorin) in LAPC patients. The aim of this study is to assess the clinical outcomes of FOLFIRINOX in patients with LAPC. Methods: Patients with LAPC who received FOLFIRINOX as an initial chemotherapy were identified via the Seoul National University Bundang Hospital database warehouse retrospectively. Demographic characteristics, disease status, chemotherapy duration and cumulative relative dose intensity (cRDI), conversion to resection and clinical outcomes were reviewed. Resectabilitywas determined based on National Cancer Comprehensive Network (NCCN) guidelines version 1.2016. Results: Fifty-one LAPC patients between Apr. 2012 and Dec. 2015 were enrolled. The median age of the patients was 60 years (30-77 years). The median overall survival (OS) of total patients was 13.3 months. The number of treatment cycles administered was 10 (2-20) and cRDI was 69.2% (35.6-91.2%). Fourteen of 51 patients (27.5%) underwent surgery and R0 resection was achieved in 11 patients (78.6%). Three patients received preoperative radiotherapy. The median OS of resected patients did not reach the 50% mark during the follow-up period compared with 13.3 months of OS in the patients without resection. Eleven of 14 resected patients did not experience recurrence during the follow-up of 10.7 months (1.8-23.5 months). The cRDI was higher in resected patients versus others (71.5 vs. 66.7%). The median time to resection was 6.7 months (3.2-14.3 months). Conclusions: FOLFIRINOX is considerable active regimen in patients with LAPC promising R0 resection rate. Future research should assess adequate duration and dose intensity of FOLFIRINOX and proper point of radiotherapy in the patients with LAPC to achieve higher rate of R0 resection.
Patterns of treatment outcomes in older patients with metastatic pancreatic cancer.
Authors: Jung Hyun Ae , Lim Sung Hee , Han Boram , Kim Ho Young , Kim Hyo Jung , Zang Dae Young , Jung Joo Young
Published: March 2017

481

Background: Although pancreatic cancers are common in older age-groups, treatment approaches and outcomes are understudied in this population. We undertook this study to compare treatment outcomes for older patients with metastatic pancreatic cancer. Methods: Data from 167 patients aged 70 years or over with metastatic pancreatic cancer from January 2010 to July 2015, were analyzed. The clinic-pathologic variables and treatment outcome retrospectively reviewed. Results: One hundred and sixty three patients were identified. Among them, only 22.1% (n=36) patients receive palliative chemotherapy. The median age was 74.0 years old (range: 70-84) in the groups of chemotherapy as compared with 78.6 years old (range: 70-94.6) in the groups of supportive care. The median survival was 9.2 months (range: 1.0-24.9) in the chemotherapy group as compared with 2.3 month (range: 0.1-31.8) in the supportive care group. Among chemotherapy group, 50% (n=18) patients receive gemcitabine-based double therapy. Nine patients (30%) receive 2nd line chemotherapy. In group of supportive care, 55.8% (n=74) were survival less than 3 months. However, the median survival except for early deaths (less than 3 months) was 6.5 months. Conclusions: The current results showed that older patient with metastatic pancreatic cancer received chemotherapy less likely. However, the survival benefit from the chemotherapy was comparable outcome with historical data. Further study of identifying older patients who would benefit from cytotoxic chemotherapy was needed.
The efficacy and safety of gemcitabine + nab-PTX for recurrence and refractory pancreatic cancer.
Authors: Saito Kei , Nakai Yousuke , Isayama Hiroyuki , Takahara Naminatsu , Mizuno Suguru , Kogure Hirofumi , Matsubara Saburo , Tada Minoru , Koike Kazuhiko
Published: March 2017

485

Background: Gemcitabine + nab-Paclitaxel (GnP) is considered as one of the standard first-line chemotherapy for advanced pancreatic cancer (PC), but its efficacy and safety of GnP in patients with refractory or recurrent (Ref/Rec) PC has not been fully reported. Therefore, we conducted this retrospective analysis of GnP in patients with Ref/Rec PC. Methods: Consecutive patients with PC who received GnP at the University of Tokyo Hospital were retrospectively studied. Clinical outcomes in patients with Ref/Rec PC were compared with those in patients with PC receiving GnP as 1st line therapy. Dose intensity was calculated as the total amout of drug given in eight weeks. Tumor response was evaluated using RECIST 1.1 and adverse event using CTCAE ver 4.0. Progression free survival (PFS) were evaluated using the Kaplan-Meier method and compared by long-rank test. Cox regression models were used to calculate hazard ratios (HRs) to evaluate the prognostic factors in patients with Ref/Rec PC and in patients receiving GnP as 1stline therapy. Results: A total of 80 patients (37 as 1st line, 18 refractory and 25 recurrent) received GnP between January 2015 and July 2016. There were no significant differences in patient characteristics between 1st line therapy group and Ref/Rec group other than sex (Male in 41 vs. 67%). In relative dose intensity (RDI), there were no significant difference (75 vs. 72%). AE rates, both hematologic and non-hematologic, did not differ significantly between two groups. RDI was 75 vs. 72% for gemcitabine and 80 vs. 79% for nab-Paclitaxel. Response rate and disease control rate were 23 and 93% vs. 11 and 86%. The median PFS were 9.0 (95%CI: 4.9-13.9) vs. 5.5 (95%CI: 3.5-8.0) months (p = 0.06) and 1-year survival rate were 42.9 vs. 14.3% (p = 0.16). In the multivariate analyses, HRs of RDI < 70 were 2.44 (95%CI: 1.07-5.49, p = 0.04) in Ref/Rec group, while the association was not significant in the 1st line group (HR 1.70 [95%CI: 0.63-4.25], p = 0.28). Conclusions: GnP was safely administered in patients with Ref/Rec PC with DI comparable to 1st line therapy. However, PFS in refractory and recurrent group tended to be short compared to those receiving GnP as 1st line therapy. DI was associated with the prognosis only in Ref/Rec PC.
Palliative chemotherapy and travel distance impacts hospice referral in patients with stage IV pancreatic cancer.
Authors: Duff Jennifer Michelle , Thomas Ryan M.
Published: March 2017

490

Background: Despite advances in chemotherapy (CTx), the prognosis for metastatic pancreatic ductal adenocarcinoma (mPDAC) is poor and while hospice is known to improve end-of-life care, referrals are often placed close to death. This may be due to accessibility issues or misconceptions that referral implies abandonment. We hypothesized that utilization of palliative CTx and travel distance to the treatment center impacts hospice referral patterns. Methods: Patients with histologically confirmed or radiographically presumed mPDAC as their initial diagnosis were retrospectively identified in a Veterans Administration Medical Center (VAMC) from 2005-2014. Demographic and clinical data were collected according to timing of hospice referral. Results: Fifty-eight mPDAC patients were identified with a median age of 63yr of which 57 (98.3%) were male. Palliative CTx was used in 26 (44.8%) patients with 32 (55.2%) not treated due to poor performance status (n = 18; 56.3%) or patient refusal (n = 14; 43.8%). Of the 52 (89.7%) patients referred to hospice, the median time from diagnosis to referral and referral to death was 2.4wk (Interquartile Range [IQR] 14.9) and 3.1wk (IQR 6.5), respectively. The median time to hospice referral was 18.7wk for patients treated with CTx vs 1.4wk for those who did not undergo therapy (p < 0.001). The median distance from residence to the VAMC was 58.5mi (IQR 77). Subset analysis for those living > 60mi vs < 60mi to the VAMC, the median time to hospice referral was 1.7wk vs 4.7wk, respectively (p = 0.1). With no significant differences between groups in age, sex, race, or disease burden, univariate analysis demonstrated that those referred to hospice > 2.4wk from diagnosis more often received CTx (p < 0.001) and lived > 60mi from the treatment center (p = 0.05). Conclusions: The majority of patients with mPDAC were enrolled in hospice and while travel distance trended to shorter time to referral, this was not significant. However, receipt of palliative chemotherapy did delay referral and those with this delay lived farther from the hospital. These data suggest that physicians delay hospice care in patients who are able to tolerate treatment and travel long distance to receive it.
Sorafenib treatment for advanced hepatocellular carcinoma: Effectiveness, safety, and controversial points.
Authors: Oikawa Takayoshi , Sawara Kei , Kuroda Hidekatsu , Takikawa Yasuhiro
Published: March 2017

496

Background: Sorafenib is only molecular target drug for hepatocellular carcinoma (HCC) in worldwide, however the effect and toxicity are different from cytotoxic anticancer agent. We evaluated that the efficacy and safety of sorafenib for unresectable HCC. Methods: This study population included fifty-eight patients that we can follow-up in 80 patients treated by sorafenib between May 2009 and May 2015 in our hospital. We evaluated the profile of sorafenib treatment (cause, initial dose, rate of changing dose), clinical response by mRECIST, adverse events by CTCAE v.4.0, Overall survival (OS) (total OS, median OS), conversion therapy and tumor response after progressive disease (PD). Results: HBV/HCV/alcohol/NBNC: 17/19/15/5, Child Pugh grade A/B: 54/4, cStage Ⅱ/Ⅲ/ⅣA/ⅣB: 1/17/15/23, extrahepatic spread(EHS) (lung /bone /adrenal gland /others): 9/5/2/7, prior treatment : 42/58 (72.4%). Cause of sorafenib treatment : TACE refractory (28%), vascular invasion or EHS (48%), initial dose 400mg (90%), changing dose :escalation (400→800); 15.5% reduction;10.3%. tumor response: objective response; 11.4%, disease control rate (DCR); 60.5%, OS: median OS 8.6 months, 3 year survival rate; 8.1%. There was significant difference in OS between Child Pugh score(CPS) (CPS:5, mOS 17.8 months, p < 0.01). Adverse events: skin disorders (17.2%), gastrointestinal disorders (17.2%), hepatobilliary disorders (17.2%), respectively. In clinical course of after PD response, 10 patients (17.2%) received hepatic arterial infusion chemotherapy for conversion therapy from sorafenib, and had 40% of DCR. Conclusions: Sorafenib is good therapeutic drug for advanced HCC and TACE refractory patients. Taking 400mg dosage of sorafenib is good response which depends on liver function. After PD response by sofafenib, conversion therapy from sorafenib has possibilities of good response.
Primary results of a phase III trial to evaluate bursectomy for patients with subserosal/serosal gastric cancer (JCOG1001).
Authors: Terashima Masanori , Doki Yuichiro , Kurokawa Yukinori , Mizusawa Junki , Katai Hitoshi , Yoshikawa Takaki , Kimura Yutaka , Takiguchi Shuji , Nishida Yasunori , Iwasaki Yoshiaki , Fukushima Norimasa , Kaji Masahide , Hirao Motohiro , Kurita Akira , Ito Seiji , Yabusaki Hiroshi , Sano Takeshi , Katayama Hiroshi , Nakamura Kenichi , Sasako Mitsuru ,   Stomach Cancer Study Group, Japan Clinical Oncology Group
Published: March 2017

5

Background: The role of bursectomy dissecting the peritoneal lining covering the pancreas and the anterior plane of the transverse mesocolon for preventing peritoneal metastasis had long been controversial. We conducted a phase III trial evaluating the role of bursectomy in patients with subserosal (SS) / serosal (SE) gastric cancer. Patient accrual had been completed on Mar. 2015. Methods: Eligibility criteria included histologically proven adenocarcinoma of the stomach; cT3(SS) or cT4a(SE). Patients were intraoperatively randomized to non-bursectomy arm or bursectomy arm. Primary endpoint was overall survival. A total of 1,200 patients were required to detect a hazard ratio of 0.77 with a one-sided alpha of 5% and 80% power. Results: Between Jun 2010 and Mar 2015, 1,204 patients were accrued from 57 institutions (non-bursectomy 602, bursectomy 602). Patients’ background and operative procedures were well balanced between the arms. After completion of patient enrollment, the second interim analysis was performed on Sep 2016, with 54% (196/363) of the expected events observed. The 3y-survival were 86.0% (95%CI, 82.7 to 88.7) in non-bursectomy arm and 83.3% (95%CI, 79.6 to 86.3) in bursectomy arm. Hazard ratio for bursectomy was 1.075 (98.5%CI: 0.760 to 1.520) with predictive probability in favor of bursectomy at the final analysis of 12.7%. These results led to early study termination based on the recommendation of the Data and Safety Monitoring Committee. Operation time was longer (median 222 min vs 254 min) and blood loss was larger (230 ml vs 330 ml) in bursectomy arm; however, the incidence of patients received blood transfusion was not different between the arms (4.8% vs 4.5%). Although the incidence of pancreatic fistula was a bit higher in bursectomy arm (2.5% vs 4.8%), the incidence of Grade 3 or higher complications was not different between the arms (11.6% vs 13.3%). Five patients in non-bursectomy arm and one patient in bursectomy showed in-hospital death. Conclusions: Although bursectomy can be safely performed without increasing morbidity and mortality, bursectomy was not recommended as a standard treatment for cT3 or cT4 gastric cancer. Clinical trial information: UMIN000003688.
Molecular variances between rectal and left-sided colon cancers.
Authors: Marshall John , Lenz Heinz-Josef , Xiu Joanne , El-Deiry Wafik S. , Swensen Jeffrey , El Ghazaly Hesham , Gatalica Zoran , Hwang Jimmy J. , Philip Philip Agop , Shields Anthony Frank , Salem Mohamed E.
Published: March 2017

522

Background: Recent analysis of CALGB 80405 showed that left sided colon tumors (LT) respond differently to biologics compared with right-sided tumors, likely due to molecular differences. Molecular variations between LT and rectal tumors remain undefined. Herein, we report our exploration of these variations. Methods: Tumors with origins clearly defined as splenic flexure to descending colon (SFT), sigmoid colon (SgT), or rectum (RT) were included. Protein expression, gene amplification and NextGen sequencing was tested. Microsatellite instability (MSI) was measured by PCR. Tumor mutational load (TML) was calculated using only somatic nonsynonymous missense mutations. Chi-square tests were used for comparative analyses. Results: In total, 1,457 primary tumors (SFT 125; SgT 460, and RT 872) were examined. When compared with SFT, RT had a higher frequency of TP53 (71% vs. 57%, p = 0.03) and APC (66% vs. 49%, p = 0.01); a lower frequency of PIK3CA (11% vs. 22%, p = 0.02), BRAF (3% vs. 15% p = 0.0001), GNAS (0.9% vs. 4%, p = 0.04), HNF1A (0.7% vs. 5%, p = 0.01), and CTNNB1(0.3% vs. 4%, p = 0.003); and a higher expression of TOPO1 (52% vs. 31%, p = 0.0001), ERCC1 (29% vs. 15%, p = 0.03), and MGMT (64% vs. 53%, p = 0.048). When compared with SgT, RT had higher expression of TLE3 (33% vs. 23%, p = 0.007), TOPO1 (52% vs. 35%, p < 0.001), TUBB3 (41% vs. 28%, p = 0.003), and MGMT (64% vs. 54%, p = 0.003). There were no differences between SFT, SgT, and RT in the frequency of PD-L1 expression (5%, 2%, and 2%) on tumor cells, PD-1 expression on tumor-infiltrating lymphocytes (54%, 42%, and 42%), or Her-2 expression (1%, 2%, and 3%) and amplification (3%, 3%, and 5%). MSI was seen in 7% of SFT, 4% of SgT, and 0.7% of RT (total LT vs. RT, p = 0.01). Mean TML was 23, 6.5, and 7 mutations (mut)/MB (332 tumors), and the portion of tumors carrying a TML of > 17mut/MB was 9%, 1.6%, and 4% for SFT, SgT, and RT, respectively. In all 3 cohorts, a TML > 17 mut/MB was highly concordant with MSI. There was a correlation between PD-1 and TML in RT (p = 0.04) but not in SFT or SgT. There were no correlations between PD-L1 and TML. Conclusions: Tumors arising in the rectum may carry genetic alterations that are distinct from LT. A better understanding of disease biology may help to identify therapeutic targets and advance precision medicine
Cost-effectiveness of surveillance after curative resection (CR) of metastatic colorectal cancer (CRC).
Authors: Lee-Ying Richard M. , Kennecke Hagen F. , Nguyen Liem , Cheung Winson Y.
Published: March 2017

526

Background: Surveillance after CR of stage I-III CRC is recommended by most major oncology organizations to detect asymptomatic recurrences. Such recurrences are more likely to benefit from early interventions such as CR of metastases. Only the NCCN recommends a surveillance schedule after CR of metastases that includes CEA testing, imaging and clinical evaluation every 3-6 months for 2 years, and then every 6-12 months in years 3 to 5. Periodic endoscopy is also recommended. It is unclear if there is cost-effective surveillance strategy for metastatic CRC after CR. Methods: A Monte Carlo micro-simulation model was constructed using a 1-month cycle length and 10 year time horizon. Surveillance strategies were compared based on NCCN guidelines, with testing every 3 months (3M) or 6 months (6M), as well as two alternate strategies of testing every 12 months (12M) or no surveillance (None) for 5 years. Recurrence, repeat CR rates, and survival outcomes were modeled from population-based outcomes of 257 patients who had CR of mCRC in British Columbia, Canada. Asymptomatic recurrences were more likely to undergo CR, compared to symptomatic ones. Additional costs, utilities, and probabilities were derived from the literature. Costs are in 2015 CAD and utilities in Quality-adjusted life years (QALY), and both discounted at 3% and half-cycle corrected. Analyses were performed using TreeAge Pro with 1000 trials and 1000 distribution samplings. Results: The incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) are listed in the Table. Increasing the frequency of surveillance tests does lead to modest gains in QALY, however, the cost of surveillance and subsequent treatment is high. Using a willingness to pay threshold of 150 000 CAD, the 6M strategy would be favored. Conclusions: In the Canadian context, the optimal surveillance strategy after CR of mCRC matches with the 6M strategy recommended by the NCCN. An additional Canadian data set will be used to externally validate the model outcomes. [Table: see text]
Importance of genetic testing for patients with multiple colorectal cancer primaries.
Authors: Elsas Caroline , LaDuca Holly , Profato Jessica , Mak Bryan
Published: March 2017

528

Background: Individuals with hereditary colorectal cancer (CRC) may be at increased risk for a second primary CRC. Therefore, a personal history of multiple CRCs may be considered an indication for genetic testing. Methods: Multi-gene panel test (MGPT) results and age at CRC diagnoses were reviewed for 7046 CRC patients who underwent testing from March 2012 to June 2016. Depending on the panel ordered, analysis of up to 49 genes associated with CRC and/or other cancers was performed. The diagnostic yield and age at CRC diagnoses were compared between patients with a history of one CRC (n=6739) and those with two or more CRCs (n=307). Results: Individuals with a history of multiple CRCs had an overall positive rate of 23.8% (n=73), as compared to 12.4% (n=836) in those with a history of one CRC (OR=2.2; p=1.1E-7; 95%CI [1.653,2.907]). In the multiple CRCs group, 77 mutations were identified as follows: MLH1 (n=29), MSH2 (n=18), MSH6 (n=5), PMS2 (n=5), biallelic MUTYH (n=5), CHEK2 (n=5), APC (n=2), BRCA2 (n=3), RAD50 (n=1), BRIP1 (n=1), BRCA1 (n=1), ATM (n=1), and PTEN(n=1). Four patients carried mutations in two different genes. Of the mutation-positive patients with multiple CRCs, 72.6% were diagnosed with their first CRC before age 50, as compared to 59.3% of mutation-positive patients with one CRC. Consequently, the mutation-positive rate increased to 36.3% in patients with multiple CRCs whose first CRC was diagnosed before age 50; whereas it was 12.4% for patients diagnosed with both CRCs at age 50 or above. Conclusions: Overall, individuals with multiple CRCs were approximately twice as likely to be mutation-positive than those with a history of one CRC. This data highlights the importance of genetic testing for those with multiple CRCs, particularly in cases where the first CRC is diagnosed before age 50. Additionally, genetic testing of patients with early onset CRC at the time of diagnosis has the potential to capture patients who may benefit from consideration of additional options to reduce their risk of developing a secondary CRC. Furthermore, mutations were identified in various genes associated with extra-colonic cancers, presenting additional opportunities for cancer risk reduction in patients and their relatives.
Characterization of tumor mutation burden (TMB) in gastrointestinal (GI) cancers.
Authors: Salem Mohamed E. , Xiu Joanne , Weinberg Benjamin Adam , El-Deiry Wafik S. , Weiner Louis M. , Gatalica Zoran , Liu Zhuqing , El Ghazaly Hesham , Xiao Nianqing , Hwang Jimmy J. , Philip Philip Agop , Shields Anthony Frank , Lenz Heinz-Josef , Marshall John
Published: March 2017

530

Background: GI cancers are generally insensitive to immune checkpoint inhibitors (ICIs). Response to ICIs has been shown to correlate with TMB. Herein, we attempt to quantify TMB in GI cancers and its correlation with PD-1/PDL-1 expression. Methods: Tumor from various GI sites: right-sided and left-sided colon cancers (RT and LT), rectal cancer (RC), small bowel adenocarcinoma (SBA), gastric adenocarcinoma (GA), anal cancer (SCCA), hepatocellular carcinoma (HCC), esophageal adenocarcinoma and squamous cell carcinoma (EA and E-SCC), biliary cancer (BC), pancreatic adenocarcinoma (PA), and pancreatic neuroendocrine tumors (PNET), were analyzed by NextGen sequencing. TMB was calculated using only somatic nonsynonymous missense mutations sequenced with a 592-gene panel. MSI was assessed by fragment analysis. Correlation of PD-1/PD-L1 expression with TMB was calculated by student’s t test. Results: In total, 1375 tumors were examined. Among the different GI cancer types, RT and LT had the highest TMB (mean: 11.6 and 9.9 mutations [mut]/megabase [MB]), whereas BC and PA had the lowest levels (mean: 5.7 and 4.9 mut/MB) (Table). Overall primary tumors had higher TMB than metastases (mean: 8.3 vs. 6.5 mut/MB, p = 0.037). Using a cut-off of 17 mut/MB to define high vs. low TMB, high TMB was seen in all 24 MSI-H and 2 MSS colon tumors with POLE mutations, but not in other MSS colon tumors (n = 325, p < 0.0001). Similarly, among 6 GA tumors tested for MSI, high TMB was seen in 2 MSI-H while low TMB was seen in the 4 MSS tumors. Overall high TMB was seen most frequently in RT (12%), GA (11%), and SCCA (8%), and least frequently in PA (1.3%) and E-SCC (0%). PD-1 correlated with TMB in some tumor types (RT and RC), as did PD-L1 (RT and HCC). Conclusions: TMB varies among GI cancers. Forthcoming prognostic analysis to assess the correlation between TMB and response to ICIs in GI cancers is underway. [Table: see text]
Awareness and misconceptions of colorectal cancer risk factors among laypersons and physicians.
Authors: Viguier Jerome , Eisinger François , Couraud Sebastien , Guibaudet Lysel , Blay Jean-Yves , Greillier Laurent , Lhomel Christine , Cortot Alexis B. , Morere Jean F. , Pivot Xavier B.
Published: March 2017

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Background: The aim of EDIFICE surveys is to improve insight into the behavior of the French population with regard to cancer prevention and participation in screening programs. The colorectal cancer (CRC) screening program is in place and targets the 50-74-yr age group. CRC prevention also relies on increased awareness of known risk factors (behavioral [BRF] or non-behavioral [NBRF]). This analysis focuses on awareness of CRC risk factors among the lay population and physicians. Methods: The 4th nationwide observational survey was conducted by phone interviews using the quota method. A representative sample of 1463 individuals with no history of cancer (age, 40-75 yrs) was interviewed between June 12 and July 10, 2014. A mirror survey on a representative sample of 301 physicians was conducted between July 9 and August 8, 2014. Interviewees were asked to cite the five main RF for CRC. Results: Heredity/family history of CRC was widely cited by physicians but far less by laypersons (LP) (95.3% vs. 26.1%, P < 0.01). Digestive disorders, age, polyps and Crohn’s disease were also cited as NBRF by 38.2%, 22.9%, 15.3% and 12.3% of physicians, respectively. In comparison, these RF were very rarely cited by LP (5.4%, 1.5%, 1.7% and 0.1%, respectively, P < 0.01). Unhealthy-lifestyle RF were cited by 86.4% and 52.7% of physicians and LP, respectively (P < 0.01): poor eating habits, ranked first for both physicians and LP (80.1 vs 46.8%, P < 0.01), including unbalanced or excessively rich diet (52.8% vs. 41.2%, P < 0.01) and excessive quantities of red meat (12.6% vs. 2.2%, P < 0.01). Among unhealthy-lifestyle RF, after poor eating habits, physicians cited first tobacco (24.3%), then alcohol (19.9%), and lack of exercise (14.6%) as other BRF. These were cited by 12.2% (P < 0.01), 16.0% (NS) and 4.7% (P < 0.01) of LP, respectively. Overweight/obesity was cited by 19.6% of physicians but by only 1.8% of LP. Conclusions: Overall, there is a lower level of awareness of CRC risk factors in lay persons than in physicians. Physicians are generally aware that heredity/family history and unhealthy lifestyle are the major RF for CRC, in line with the widely recognized RF. In contrast, lay persons rank BRF highest, and notably those related to poor eating habits.
Performance of 18FDG-PET in the management of non-metastatic HIV+ anal squamous cell carcinoma (ASCC).
Authors: Baba Hamed Nabil , Deplanque Gael , Kassis Raid , Gatineau Michel , Staudacher Lionel , Chaiba Imene , Savinelli Francesco , Sverdlin Robert , Maiga Oumou , Marin Jean Luc , de Parades Vincent , Lemarchand Nicolas , Marty Olivier , Levoir Damien , Loriau Jerome , Zerbib Eric , Zins Marc , Boulay Isabelle , Raymond Eric
Published: March 2017

541

Background: ASCC remains rare, but the incidence has been increasing over the last decade, especially in patients with HIV infection (HIV+). A recent meta-analysis demonstrated the usefulness of 18FDG-PET in initial staging and response assessment in ASCC. HIV+ patients may develop opportunistic infections which can cause false positives lymph nodes on PET scanning and, therefore, our objective was to evaluate performance of 18FDG-PET in HIV+ patients. Methods: Retrospective analysis of consecutive patients with non-metastatic ASCC, treated in our institution during six years. HIV+ patients were analyzed separately in two groups according to their lymph nodes status, group 1 (Gr 1): N0, group 2 (Gr 2): N1, N2, N3. Results: A total of 87 patients with ASCC were analyzed, including 24 HIV+ patients (21 males, median age was 53 for male and 50 for women). There were 15 patients in Gr 1 and 9 in Gr 2. All patients performed conventional imaging (MRI and CT-scan). In Gr 1, 12/15 patients had 18FDG-PET, it resulted in upstaging nodal disease in 2 patients. In Gr 2, 6/9 patients had 18FDG-PET, it resulted in upstaging nodal disease in 1 patient and downstaging nodal disease in 2 patients. Both of sensibility and specificity of FDG-PET were 83% in our HIV+ population. All patients underwent Mitomycine C and 5FU based chemoradiation or exclusive radiation therapy. Mean radiation dose received was 63.3Gy in G1 and 63.9Gy in G2. 18FDG-PET drives a modification in treatment strategy in only 1 patient in both of groups. Post-treatment 18FDG-PET was performed 4 months after treatment completion. Among patients who had post-treatment 18FDG-PET, a metabolic complete response was observed in 6/11 patients in Gr 1 and 3/5 patients in Gr 2. Survival at 5 years was 89% and 75% in Gr 1 and Gr 2, respectively. Conclusions: Based on our experience, 18FDG-PET drives substantial changes neither in staging nor in therapeutic strategy for ASCC HIV+ patients, however, it may be useful for radiation therapy planning.
Incidence of colorectal carcinoma following liver transplantation: A retrospective analysis using the United Network for Organ Sharing (UNOS) database.
Authors: Krishnan Mridula , Gharzai Laila , Qurie Ahmad , Diab Osama , Narayanan Mahesh Anantha , Vivekanandan Renuga , Walters Ryan W
Published: March 2017

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Background: Since 1988, approximately 145,000 liver transplants (LT) have been performed in the United States, with 7,127 in 2015 alone. Several malignancies occur more frequently in solid organ transplant recipients. Studies have shown increased risk of Colorectal cancer (CRC) post LT in adults with primary sclerosing cholangitis, whether the risk of de novo CRC is increased or not remains controversial. Methods: A retrospective analysis was conducted using the UNOS database. Between-group differences in CRC rates were compared using Fisher’s exact test whereas, the differences in observed years between liver transplant and CRC were compared using negative binomial regression models. Results: We retrospectively analyzed 12,337 recipients of LT within the UNOS database. The overall incidence of CRC post LT was estimated to be at 3.8 percent. Interestingly, the incidence was higher in women and non-obese recipients. All immunosuppressive agents within the limits of the database were analysed for maintenance and anti-rejection. The two agents with some increase in incidence were cyclosporine and cellcept but this was statistically insignificant.(Table 1) Women and elderly ( > 65 years) were likely to develop CRC approximately 25 percent earlier than men and younger patients (p = 0.003 and p = 0.001, respectively). Conclusions: Studies have shown a trend toward increased incidence of CRC post LT. These studies were limited by the sample size and were single-center trials. To date there are no elaborate guidelines on surveillance of CRC in LT recipients. In our study there was a shorter interval to development of CRC in older patients and women, suggesting that this population may benefit from early initiation of screening. [Table: see text]
Effect of colon cancer sidedness compared to tumor biology on stage-specific survival.
Authors: Dehal Ahmed , Vuong Brooke , Graff-Baker Amanda N , Lee Jihey , Bilchik Anton , Goldfarb Melanie R
Published: March 2017

543

Background: Recent studies have reported a survival difference between right colon cancer (RCC) and left colon cancer (LCC) but were limited by lack of data on surgical therapy and underlying tumor biology including microsatellite instability (MSI) status. Our objective was to examine the influence of tumor sidedness on stage-specific survival after adjustment for those factors using a large national database. Methods: Adult patients with primary invasive colon cancer were identified from the National Cancer Data Base (NCDB) between 2009 and 2012. Cecum, ascending colon, hepatic flexure, and transverse colon were classified as “RCC” and sigmoid, descending colon, and splenic flexure were classified as “LCC”. Differences in 3-year overall survival (OS) between RCC versus LCC, stratified by stage, were obtained. Results: Of 24,092 patients, 9,095 (37.75%) presented with a LCC and 14,997 (62.25%) with a RCC. After adjustment for confounding factors, including demographics, MSI, KRAS, nodal retrieval and treatment, patients with RCC stage I, III, or IV had a 31-35% decreased OS compared to those with a LCC. However, in patients with stage II disease, RCC had a 15% improvement in OS compared to LCC (Table 1). MSI positivity was not significantly different in RCC versus LCC stage for stage nor did it contribute to decreased OS for either side. Conclusions: Colon cancer sidedness is an independent risk factor for decreased survival after adjusting for potential confounders including tumor biology and treatment characteristics. For patients with stage I, II, and IV disease, RCC portends a decreased survival compared to LCC, whereas the opposite is true for patients with stage II disease. Further research is needed to elucidate the exact the role of sidedness in risk-profiling and staging for colon cancer patients. [Table: see text]
Preoperative evaluation of heat shock protein 47 expression to identify patients with colorectal cancer with lymph node metastasis and poor prognosis.
Authors: Mori Koichiro , Toiyama Yuji , Okugawa Yoshinaga , Ichikawa Takashi , Nagano Yuka , Oki Satoshi , Imaoka Hiroki , Okigami Masato , Fujikawa Hiroyuki , Hiro Junichiro , Saigusa Susumu , Kobayashi Minako , Inoue Yasuhiro , Mohri Yasuhiko , Kusunoki Masato
Published: March 2017

546

Background: Accumulating evidences reveal that overexpression of Heat shock protein 47 (HSP47) increase cancer progression, and that HSP47 expression in the tumor-associated stroma serve as diagnostic marker in various cancers. In addition, we recently performed immunohistochemistry to evaluate HSP47 expression in surgical colorectal cancer (CRC) specimens, and showed that the count of HSP47 positive spindle cell in cancer stroma was significantly associated with lymph node (LN) metastasis, early recurrence and poor prognosis in CRC patients. Thus, evaluating HSP47 expression in CRCs preoperatively may be valuable for planning the treatment of patients with CRC. In this study, we quantified the messenger RNA(mRNA) expression of HSP47 in CRCs by using preoperative biopsy samples, and analyzed the association between HSP47 mRNA expression and clinico-pathological factors including prognosis in patients with CRC. Methods: A total of 139 CRC samples, which were taken by biopsy before surgery at Mie University Hospital from 2000 to 2005, were enrolled. HSP47 gene expression was determined by quantitative real-time reverse transcription–PCR using Power SYBR Green PCR methods. Results: All CRC patients were classified according to the tumor-node-metastasis (TNM) classification system as follows: stage I (n = 33); stage II (n = 44); stage III (n = 33), and stage IV (n = 29). High HSP47 expression in CRC was significantly associated with higher T stage (p = 0.0163), LN metastasis (p = 0.0186), vessel invasion (p = 0.0328) and higher TNM staging (p = 0.0115). Kaplan-Meier analysis showed that patients with high HSP47 expression had significantly poorer overall survival (OS) than those with low (p = 0.0003). Furthermore, multivariate analyses revealed that HSP47 expression was an independent predictive marker for LN metastasis and poor OS in CRC patients, respectively (LN metastasis; OR; 2.3946, p = 0.0249, OS; HR; 2.7407, p = 0.00224). Conclusions: In conclusion, quantification of HSP47 expression using biopsy samples can identify the CRC patients who may suffer from LN metastasis and poor prognosis, preoperatively.