bluuebunny/crossref_metadata_2025 huggingface dataset:
FOLFIRINOX for the treatment of advanced pancreatic cancer: U.K. West Midlands experience.
Authors: Jain Ankit , Scott-Brown Martin , Correa Peter Denzil , Sothi Sharmila , Davies Amy , Candish Charles , Peake David , Tsalic Medy , Punia Pankaj , Ma Yuk Ting
Published: February 2017

450

Background: The PRODIGE 4/ACCORD 11 trial demonstrated that FOLFIRINOX significantly improved response rates and survival in patients with metastatic pancreatic cancer, compared to gemcitabine. However this regimen is associated with significant toxicity. We have thus analysed the safety, tolerability and efficacy of FOLFIRINOX given outside a clinical trial setting. Methods: A retrospective analysis was conducted on all patients treated with FOLFIRINOX for advanced pancreatic cancer between July 2012 and July 2014, within the West Midlands region in the UK. Data was collected on baseline demographics, disease stage, toxicity and response to chemotherapy. Results: A total of 60 patients were identified (28 locally advanced, 32 metastatic). The median age was 59 (range 34-74) and 12% of patients were aged 70 or over. The primary tumour was located in the head of the pancreas in 68% of patients and 38% of patients had a biliary stent. All patients had an ECOG performance status of 0 or 1 (45% and 55% respectively), and had received no prior chemotherapy for advanced pancreatic cancer. FOLFIRINOX was commenced at reduced doses in 79% of patients, and subsequent dose reductions were required in 81% of patients. The median number of FOLFIRINOX cycles administered was 6 (range 1-14) but 33% of patients currently remain on treatment. Hospital admissions were required in 58% of patients but only 22% of hospital admissions were for neutropenic sepsis. FOLFIRINOX was discontinued in 30% of patients due to toxicity. There were no treatment related deaths. Of 40 patients who were eligible for assessment of response, 38% achieved a partial response and a further 45% achieved stable disease. Four patients with LA pancreatic cancer became suitable for curative surgical resection following chemotherapy; 2 of these also received chemoradiotherapy. The median overall survival for patients with metastatic disease was 12 months and the median overall survival for patients with locally advanced disease has not been reached. Conclusions: Our data shows that FOLFIRINOX can be safely delivered in a real world setting. Even with reduced doses, the response rates and survival outcomes are comparable with the results from the PRODIGE 4/ACCORD 11 trial.
Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios at the time of chemoradiation to predict survival in resected pancreatic cancer patients.
Authors: Xu Vanessa , Choi Enid , Hanlon Alexandra , Regine William , Chuong Michael David
Published: February 2017

452

Background: Higher pre-treatment neutrophil-to-lymphocyte ratio (NLR) and lower platelet-to-lymphocyte ratio (PLR) are independent predictors for worse survival in cancer patients. The effect of chemoradiation (CRT) on NLR and PLR in pancreatic cancer patients who also undergo surgical resection has not been reported. Methods: A retrospective review was performed of pancreatic cancer patients treated at our institution with CRT either prior to or after surgery with curative intent. Overall survival was evaluated using Kaplan-Meier method. Univariate and multivariate Cox regression models were applied to evaluate the independent prognostic significance of NLR and PLR. Results: After excluding patients who did not have surgery, who received palliative radiation doses, or who had incomplete medical records, 81 out of 282 patients remained with median age 62 years (35-86). Of these, 24 (29.6%) were borderline resectable (BR) and received preoperative CRT while 57 (70.4%) received adjuvant CRT. Median total dose and number of fractions were 50.4 Gy (30-59.4) and 28 (5-33), respectively. Median pre-CRT and post-CRT NLR were 2.9 and 7.8, respectively. Median pre-CRT and post-CRT PLR were 211.3 and 457.5, respectively. Most patients had a decrease in NLR (85.2%) and PLR (72.8%) after CRT, with median changes of -4.95 for NLR and -178.33 for PLR. Cox proportional hazards analysis showed a trend towards significance for pre-CRT NLR (p=.08) regarding OS. A significant relationship was found between relapse free survival and both pre-CRT NLR (p=0.02) and PLR (p=0.01). The difference or percent change of neither NLR nor PLR was found to correlate with clinical outcomes. Conclusions: This is the first study to evaluate the effect of CRT on NLR and PLR in resected pancreas cancer patients. Similar to other reports, our data indicate that a significant relationship exists between NLR, PLR, and clinical outcomes. Identification of clinically meaningful NLR and PLR cut-off points for resected pancreatic cancer patients who also receive CRT is needed.
Outcome and cause of death of hepatocellular carcinoma patients with extrahepatic metastases.
Authors: Shiba Satoshi , Kondo Shunsuke , Sakamoto Yasunari , Sasaki Mitsuhito , Koga Futa , Hosoi Hiroko , Morizane Chigusa , Ueno Hideki , Okusaka Takuji
Published: February 2017

456

Background: Sorafenib is an orally active multi-kinase inhibitor that has been approved for the treatment of advanced hepatocellular carcinoma (HCC). Advanced HCC patients often exhibit two co-existing and life-threatening factors, cancer and cirrhosis, complicating prognostic evaluations. The present study investigated the survival and causes of death of HCC patients with extrahepatic metastases in the sorafenib era. Methods: We retrospectively analyzed 72 HCC patients with extrahepatic metastases who had received sorafenib. The causes of death among the HCC patients were classified as either hepatic causes (HC) or non-hepatic causes (NHC). Each cause of death was analyzed in the two subgroups. We then compared and assessed their clinical features and outcomes using the Chi square test, the Kaplan-Meier method, and a multivariate analysis. Results: Of the 72 HCC patients (female/male, 12/60), 50 patients had died at the time of the analysis. The median age was 66 (range, 30-84) years. At the time when sorafenib was started, the number of patients with a performance status of 0, 1, or 2 was 63 (88%), 8 (11%), and 1 (1%), respectively, and the number of patients with Child-Pugh class A, and B were 67 (93%), and 5 (7%), respectively. The median survival time and the 1-year survival rate were 11.8 (95% confidence interval 5.3-18.3) months and 49.7%, respectively. The incidence of HC and NHC was 29 (58%) and 21 (42%), respectively. Differences between the HC group and the NHC group were examined according to the patient characteristics, and the following significant differences were observed: main portal vein invasion (P<.05), intrahepatic tumor stage (P<.05), alpha-fetoprotein (AFP) (P<.05), and the des-gamma-carboxy-prothrombin level (P<.05). A multivariate analysis showed that portal vein invasion (hazard ratio [HR] = 2.29, P<.05), a Child-Pugh B status (HR = 7.19, P<.01), and high serum levels of AFP (HR = 2.18, P<.05) were independent predictors of a poor outcome, respectively. Conclusions: This study revealed differences in the clinical characteristics at the time of the start of sorafenib between patients with HC and NHC death. The present results may be useful in the design and analysis of future clinical trials.
A retrospective study of FOLFOX in the treatment of patients with advanced duodenal adenocarcinoma: A Japanese single-center experience.
Authors: Yamada Ikuhiro , Ozaka Masato , Ishii Hiroshi , Sasahira Naoki , Takano Kouichi , Matsuyama Masato , Sasaki Takashi , Saito Kei , Osumi Hiroki , Suenaga Mitsukuni , Igarashi Masahiro
Published: February 2017

457

Background: Duodenal adenocarcinoma is a rare tumor with poor prognosis. There is little data on the efficacy of chemotherapy for this disease. Methods: The current study included data from all consecutive patients who were diagnosed as having duodenal adenocarcinoma at our hospital between October 2008 and December 2013. Selection criteria were as follows: patients who 1) had histologically confirmed duodenal adenocarcinoma, 2) were diagnosed as having unresectable or recurrent disease, and 3) received first-line chemotherapy with infusional 5-FU, leucovorin and oxaliplatin (FOLFOX). We examined efficacy and toxicity of FOLFOX therapy from the case cards and analyzed their survival data. Results: There were 20 patients who met the selection criteria. The median age was 67.5 years (range, 35-76). Of the 20, 11 (45%) were male, 17 (85%) had a good performance status, 15 (75%) had received resection of the primary tumor, and 13 (65%) had a liver metastasis. They received median of 8 (range, 1-32) chemotherapy cycles. There was no complete response. Of the 20, 4 (20%) achieved partial response, 9 (45%) remained stable disease, 6 (30%) showed progressive disease and the remaining one did not have a CT evaluation. The median progression free survival and overall survival months from the initiation of FOLFOX therapy were 5.0 and 11.7, respectively. Grade 3/4 toxicities were observed in 9 (45%). Although there was no febrile neutropenia, grade 3/4 neutropenia was observed in 7 (35%). Treatment-related death due to pneumonitis was documented in one. Whereas prognostic factor was not found in multivariate analysis, a peritoneum metastasis tended to be associated with poor progression free survival (p=0.06). Conclusions: The FOLFOX therapy shows moderately activity with acceptable toxicities for the treatment of advanced duodenal adenocarcinoma.
Effect of renin-angiotensin system (RAS) inhibition on survival in advanced ductal adenocarcinoma (PDAC).
Authors: Winston Rachel , Weiss Glen J. , Baldwin Ashley , Frank Samuel , Tims Lucas , Brooks Nakia Lashawn , Kundranda Madappa N.
Published: February 2017

464

Background: Advanced PDAC portends a poor survival due to several factors including development of resistance to therapies via tumor-stromal interactions. In preclinical studies, RAS inhibition has been implicated in PDAC development due to its anti-inflammatory effect by reducing pancreatic inflammation and fibrosis via suppressed activation of pancreatic stellate cells. Methods: A retrospective analysis was conducted at two institutions in North America of patients (pts) with advanced PDAC receiving palliative chemotherapy. Data collection included age, gender, ECOG, prescription for an angiotensin I-converting enzyme inhibitors (ACEIs) and/or angiotensin II type-1 receptor blockers (ARBs), and overall survival (OS). Statistical analysis included Kaplan Meier survival analysis along with the log-rank test to compare treatment strata. Additionally, multivariate analyses were performed using a Cox proportional hazard model. Results: The 403 pts included had a median age of 61 years (range: 25-86 yrs); 176(43%) were women and 329 (>80%) had an ECOG performance status of 0 or 1. A majority of patients received combination therapy that was either gemcitabine or 5-flurouracil based. 57 (14%) received ACEIs and 25(6.2%) received ARBs. There was no statistically significant difference in median OS between those prescribed ACEI or ARB and those who were not (13.7 vs. 14.2 months; p=0.432). Subgroup analysis of ACEI vs. no ACEI or ARBs vs. no ARBs was similar (ACEI =13.8 vs. 14.2 months (p=0.741) and ARB=13.7 vs. 14.2 months (p=0.405). In addition, ACEI vs. ARB showed similar results 13.8 months (ACEIs) vs. 13.7 months (ARBs) (p=0.687). Conclusions: Our study did not demonstrate a statistically significant difference in OS between advanced PDAC patients in North America that were prescribed ACEI, ARB, or to those who were not. Compliance with taking prescribed ACEI or ARB medications could not be determined. A prospective phase 2 study in a Japanese population using the combination of gemcitabine and candesartan (an ARB) did not demonstrate a survival benefit with the combination. Based on these clinical evaluations, use of ACEI or ARB to take advantage of blocking RAS in advanced PDAC cannot be supported.
Comparative efficacy of S-1 versus best supportive care in advanced hepatocellular carcinoma.
Authors: Yu Pengfei
Published: February 2017

466

Background: S-1, an oral fluoropyrimidine derivative, has been shown to be clinically effective against hepatocellular carcinoma (HCC). We carried out a retrospective study to evaluate the efficacy of S-1, compared to best supportive care (BSC) in patients with advanced hepatocellular carcinoma. Methods: From 2009.12 to 2013.12, 32 cases of advanced hepatocellular carcinoma (the presence of extrahepatic metastasis or locally advanced disease not amenable to surgical resection or other locoregional therapies) were retrospectively analysed. 18 patients received S-1 (80 mg/m2/day, administered during days 1~14 and repeated every 21 days) and 14 patients received best supportive care (BSC). The time to progression (TTP), overall survival (OS) and safety were assessed. Results: 17 of 32 (53.1%) patients had metastatic disease, including the retroperitoneal lymph nodes (7 cases), lung (4 cases), supraclavicular lymph nodes (3 cases), abdominal wall (3 cases), brain (2 cases) and adrenal glands (2 cases). 12 patients (37.5%) had portal vein tumor thrombus. The two groups were well matched at baseline. In S-1 group,a total of 63 cycles were administered with median of 3.5 cycles (range, 2~7).The most common grade 3/4 toxicities were thrombocytopenia (28.1%), neutropenia (21.8%), elevated serum aspartate aminotransferase levels (15.6%) and rash (9.4%). A patient (5.6%) had a partial response,11 (61.1%) had stable disease, and 6 (33.3%) had progressive disease. Median TTP was 4.7 months in the S-1 group compared with 2.3 months in the BSC group (P=0.013). Overall survival was 15.1 months in patients treated with S-1, compared with 8.3 months in those who received BSC (P=0.027). Conclusions: S-1 showed an acceptable safety profile and benefit in survival in patients with advanced HCC.The conclusion needs further evaluation in randomized clinical trials.
Changing epidemiology of gastric sarcomas in the United States.
Authors: Lin Albert Y. , Ravdin Peter
Published: February 2017

47

Background: The introduction of imatinib as targeted therapy for the treatment of gastrointestinal stromal tumors (GIST) has supplied a strong impetus for the reclassification of gastric sarcomas (GS). We examined the changes in the incidence and mortality over the last 20 years for GS subtypes using the Surveillance, Epidemiology, and End Results (SEER) database over the last 20 years. Methods: Based on information from SEER, GS cases were identified by primary cancer site and ICD-O-3 codes. SEER*stat was used to make estimates of incidence and cause specific survival. Joinpoint software was used to test for trends. Results: The overall incidence of GS increased of from 1991 and to 2011 from 2.9 (standard error [SE] 0.4) to 6.6 (SE 0.6) cases per million per year. The histologic subtypes of changed over this time interval with the leiomyosarcoma being initially the leading GS subtype with an incidence from 2.3 (SE 0.4) decreasing to 0.1 (SE 0.1). The incidence of gastric GIST increased from 0.1 (SE 0.1) to 6.3 (SE 0.6) representing 95% of all GS cases in 2011. For GS test for trend with Joinpoint model did not detect a discontinuity in the trend (occurring at a rate of 4.7% [p < 0.001]) relative increase per year. Much of the total GS increase in incidence was for localized disease with the incidence rates which increased from 1.2 to 4.5 cases per 10^6/year a relative increase of 6.8% (p < 0.01) per year. During this period the 3-year cause specific mortality improved for localized GS from 9.4% to 0.9%. Improvements were also seen for mortality outcomes for regional and distant disease. Conclusions: Between 1991 and 2011, more than a doubling of incidence of GS was observed with a concurrent rapid change in GIST - most in localized disease and a dramatic improvement in its outcome. It seems unlikely that this is due to changes in the underlying biology of the disease, or to imatinib alone, but may be, in part, due to changes in diagnostic techniques or pathologic evaluation
Evaluation of dynamic tumor-tracking IMRT for patients with pancreatic cancer using gimbaled linac of vero system.
Authors: Nakamura Akira , Nakamura Mitsuhiro , Itasaka Satoshi , Kishi Takahiro , Ishihara Yoshitomo , Mukumoto Nobutaka , Akimoto Mami , Mizowaki Takashi , Kokubo Masaki , Hiraoka Masahiro
Published: February 2017

481

Background: We have started dynamic tumor-tracking intensity-modulated radiotherapy (DT-IMRT) using the gimbaled linac of Vero4DRT from June 2013. This study reports the first clinical evaluation of DT-IMRT for patients with locally-advanced pancreatic cancer (LAPC). Methods: Five patients with histologically proven LAPC and written informed consent were enrolled. One Visicoil fiducial marker was percutaneously or endoscopically inserted inside the tumor. DT-IMRT was performed with the gimbaled X-ray head which can swing the intensity-modulated beam towards the moving tumor based on a correlation model of external-to-internal motion. During the beam delivery, the Visicoil was continually monitored with the kV and MV imagers mounted on the gantry of the Vero4DRT, and the correlation model was recalibrated when needed. An escalated dose of 45-51 Gy in 15 fractions was delivered to the planning target volume (PTV) with concurrent full-dose gemcitabine (1,000 mg/m2). The following factors were evaluated: the differences in PTV volume and the absolute volume receiving 39Gy or 42Gy (V39 or V42) for stomach and duodenum between DT-IMRT and a conventional technique; positional errors between the predicted tumor and irradiated positions; in-room time for the daily treatment; and radiotherapy-induced toxicities. Results: The mean reduction in PTV volume was 15%. The planned V39/V42 to stomach and duodenum were reduced approximately by 92%/96% and 83%/91%, respectively, when compared with a conventional technique, while tumor doses were comparable. The 95th percentiles of positional errors were within 2.5, 2.8, and 3.2 mm in left-right, anterior-posterior, and cranio-caudal directions, respectively. The mean in-room time was 24.5 minutes. All patients completed the planned radiotherapy and concurrent full-dose gemcitabine. There were mild hematological toxicities, but no severe gastrointestinal toxicities directly attributable to the DT-IMRT. Conclusions: A safe dose-intensification was achieved applying DT-IMRT for patients with LAPC, based on the high accuracy for tumor-tracking and the reductions in PTV volume and high-dose volume in critical organs.
Efficacy of chemotherapy after self-expanding metal stent placement for gastric outlet obstruction caused by an unresectable malignant tumor.
Authors: Yamamoto Taikan , Miyashita Kouichirou , Shimada Ken , Sekikawa Takashi , Uto Yu , Nunoue Toshikazu , Kaga Yasuhiro , Kitahara Yu , Saito Yusuke , Kobayashi Kouji , Kinugasa Eriko
Published: February 2017

484

Background: Gastric outlet obstruction (GOO) is a late complication of advanced and metastatic malignant tumors. Self-expanding metal stent (SEMS) placement is a safe and effective palliative treatment for patients with GOO. In general, the median survival time after SEMS placement for GOO is approximately 90 days, and advanced chemotherapeutic treatment could further improve prognosis. Methods: This retrospective study aimed to analyze the efficacy of chemotherapy after SEMS placement on improvement of oral intake and survival time. Eight patients with symptomatic malignant GOO were treated by SEMS placement in our hospital. Surgical bypass could not be performed due to severe advanced malignant tumors. Patients were classified into two groups depending on whether they received chemotherapy after SEMS placement. Group A included five patients who were treated with palliative therapy alone (median age: 72 years; cases 1, 2, 3, and 4 with advanced gastric cancer, and case 5 with advanced pancreatic carcinoma). Group B included three patients who were treated with palliative therapy, followed by chemotherapy (median age: 68 years; case 6 with advanced pancreatic cancer treated with gemcitabine chemotherapy; case 7 with advanced gastric carcinoma treated with TS-1 and paclitaxel chemotherapy; and case 8 with duodenal stenosis due to advanced colonic carcinoma treated with irinotecan and cetuximab chemotherapy after SEMS placement). We estimated the gastric outlet obstruction scoring system (GOOSS ; no oral intake: 0; only liquids: 1; soft solids: 2; low-residue or full diet: 3) and survival time as the main outcomes. Results: SEMS placement using endoscopy was successful in all cases. No complications occurred after the procedure. Performance status did not change after SEMS placement. GOOSS improved from 0 to 1 in group A and from 0 to 2 in group B. Median survival time was 68 days in group A and 188 days in group B. We considered chemotherapy after SEMS contributed lifetime. Conclusions: Our study findings indicate that SEMS placement is a safe and effective method for managing malignant GOO and that chemotherapy after SEMS placement can improve diet intake and prognosis.
Results of surgical treatment of colorectal cancer liver metastases in Latvia oncology center.
Authors: Sivins Armands , Lauka Lelde , Ancans Guntis , Gerkis Sergejs , Pcolkins Andrejs , Krumins Viesturs , Nemiro Ineta , Strazdina Arta , Kreice Ilona , Plate Signe , Kasperova Svetlana , Boka Viesturs , Leja Marcis
Published: February 2017

485

Background: Colorectal cancer (CRC) is the third leading cause of cancer death. At the time of diagnosis 25% of patients present with stage IV disease and out of all CRC patients 50% develop liver metastases. About 15% of them have initially resectable disease. Surgical resection is the best treatment option as it is associated with longer survival. Latvia Oncology center (LOC) provide expertise in managment of all cancers, including metastatic CRC. Methods: Data about CRC patients with surgicaly treated liver metastases was colected and analysed from Latvia Oncology center in period 2011-2014. This data is also included in LiverMetSurvey international registry of patients operated for CRC liver metastases. 66 patients underwent hepatectomies, 10 patients had 2 or more surgeries due to a reccurent disease. Results: 77 surgeries were performed, 31 were hemihepatectomies and 46 were limited resections. Sinchronous surgery for liver metastases and primary tumor were performed in 19 cases: 11 for left colon cancer, 6 for rigt colon cancer and 2 for rectal cancer. Initially resectable liver disease was found in 70 cases. Unilateral metastases were diagnosed in 61 cases while there were 17 cases of bilateral disease. Postoperative complications developed in 18 patients, 5 of those after sinchronous surgeries for primary tumor. In 10 cases complications developed after major anatomical right sided hemihepatectomy and in 8 cases after atypical resections. Most frequent hepatic complications were infected collection in hepatic loge (n=9), non infected collection (n=3) and biliary leak (n=3); all of those were successfully treated with percutaneous dreinage. 1 patient died due to a postoperative liver insufficiency after right sided hemihepatectomy for recurrent disease. Conclusions: Overall 77 hepatectomies were performed, mostly limited non anatomical resections. In majority of patients 1 or 2 metastases were diagnosed. Initally resectable were 89% of cases. Mass of postoperative complications developed after major hepatectomies, were liver related and successfully treated with minimally invasive procedures. Complication rate (16%) in LOC is comperable to other Europian centers.
Safety and feasibility of S-1 adjuvant chemotherapy for pancreatic cancer in elderly patients.
Authors: Murakawa Masaaki , Aoyama Toru , Katayama Yusuke , Asari Masahiro , Sawazaki Sho , Yamaoku Koichiro , Kanazawa Amane , Higuchi Akio , Kobayashi Satoshi , Shiozawa Manabu , Yamamoto Naoto , Yukawa Norio , Yoshikawa Takaki , Ohkawa Shinichi , Rino Yasushi , Masuda Munetaka , Akaike Makoto , Morinaga Soichiro
Published: February 2017

486

Background: The safety and feasibility of starting S-1 adjuvant chemotherapy for pancreatic cancer has not been evaluated in elderly patients. Methods: The patients who underwent curative D2 surgery for pancreatic cancer were selected to this retrospective study. The patients were diagnosed within stage I to III disease, and received adjuvant S-1 at our hospital. Patients were categorized into two groups; non-elderly patients (age<70 years: group A) and elderly patients (age≥70 years: group B). The toxicity and drug continuation rates in the two groups were compared. Results: Total 40 patients were evaluated in this study. There were no grade 3 and 4 toxicities. The incidences of grade 2 hematological toxicities were 0% in group A and 11% in group B. The incidences of grade 2 non-hematological toxicities were 50% in group A and 27.8% in group B. The differences in both groups were not significant. The continuation rate at 6 months was 55.7% in group A and 72.7% in group B, and there was also no significant difference in the groups. Conclusions: These results suggest that S-1 adjuvant chemotherapy for pancreatic cancer is safe and feasible, regardless of the age of the patient; especially in elderly patients.
Therapy response of Chinese herbal medicine in primary liver cancer.
Authors: Gong Yongling
Published: February 2017

488

Background: Aiming at starting the ball rolling and contributing humble effort to promote Chinese traditional medicine, we report successful cases of Chinese herbal decoction for primary liver cancer. Methods: Conventional therapy of surgical resection and artery catheterization chemotherapy was applied in cases reported. In the meantime, we administered Chinese medicine (Gan Decoction, mixed with a variety of effective herbal components) to help them to recover from poor condition. Results: After taking the Chinese herbal decoction for months, the tumour marker (AFP, CA19-9) level dramatically decreased to the normal range. Most residual intrahepatic metastatic sites reduced according to ultrasonography/CT imaging, and the patient felt free from the complaint of abdominal discomfort. The quality of life has been greatly improved, we managed to have prolonged the PFS (Progression-Free-Survival) and TTP (Time-to-Progression) from the onset to date. Conclusions: Chinese medicine considers human body as a dynamic platform in which all organs are correlative and bind each other. Each case showed distinguished liver cancer progression and heterogeneity with individual therapy response. Our report suggested that Chinese herbs might be an additional choice with its better benefits and tolerability in the treatment of primary liver cancer.
Cross-sectional analysis of patients with non-mGC in China: An update of EVIDENCE gastric cancer registry study.
Authors: Wang Xin , Ji Jiafu , Zheng Zhichao , Zhang Helong , Zhou Weiping , Su Wuyun , Luo Qi , Guo Qunyi , Li Xiaoyi , Tang Yong , Xu Jian-Ming , Tao Feng , Li Wei , Li Xiaoqin , Qin Shukui , Yu Eric Chi-Wang , Yang Chen , Shen Lin
Published: February 2017

49

Background: According to WHO estimation, > 400,000 new cases of gastric cancer have occurred in 2012 in China, making it the second most common malignancy in the country. However, little is known about epidemiological data of gastric cancer in China. This analysis aimed to evaluate clinicopathological and socioeconomic characteristics of Chinese patients with non-mGC. Methods: EVIDENCE was a prospective registry study. 2,600 patients with newly diagnosed gastric cancer from 85 hospitals across China were planned to be enrolled into this study. Patients who have histopathologically confirmed diagnosis of gastric cancer and corresponding HER2 IHC status diagnostic results within 6 months before enrollment are eligible. According to overall stage of disease, HER2 status, and use of trastuzumab (Herceptin®), patients are continuously assigned to 5 different cohorts until number of patients has reached the designated limit of each cohort. Results: Until 31st May 2014, 885 eligible patients were continuously enrolled before completion of recruitment of any cohort. Of these patients, 538 (60.8%) patients who were diagnosed with non-mGC were included in this analysis. In this population, 15.6% of these patients were HER2-positive (IHC3+ or IHC2+/ISH+), 73.6% were male, median age of diagnosis was 60 (range: 26-85). 75.3% (403/535) of patients were diagnosed with upper endoscopy, 65% (348/535) with biopsy, and 23.9% (128/535) with surgery. Primary tumor site of 37.2% (191/514) of patients was at the antrum (the lower third of stomach), 22.8% (117/514) was at the body (the middle third of stomach), 17.7% (91/514) was at the gastro-oesophageal junction, and 10.9% (56/514) was at the fundus (the upper third of stomach). 43.0% were former or current smokers, 30.3% had reported light to moderate alcohol consumption habit. Most of the patients (39.5%) had completed primary education or below, 53.6% reported their family annual income of RMB 35,000 (US$5,700) or below. Conclusions: Analysis of clinicolpathological and socioeconomic characteristics of Chinese patients with GC will help to improve disease management of these patients. Patient recruitment and additional analyses will be continued as planned. Clinical trial information: NCT01839500.
Endoscopic response evaluation of gastric primary lesion for chemotherapy compared to CT in advanced gastric cancer.
Authors: Chin Keisho , Yamamoto Yorimasa , Fujisaki Junko , Ogura Mariko , Shinozaki Eiji , Suenaga Mitsukuni , Mizunuma Nobuyuki
Published: February 2017

50

Background: Significance of evaluation of gastric primary lesion with endoscopy remains unclear in chemotherapy (CTx) for advanced gastric cancer (AGC). Endoscopic evaluation is not necessary in RECIST. Methods: We compare the response of chemotherapy using RECIST by CT with or without upper GI endoscopy in AGC cases retrospectively. Among 175 cases of unresectable AGC treated by CTx in our institution between 2004 and 2008, we reviewed 141 evaluations in 74 cases which were examined by both endoscopy and CT within 2 weeks before and after CTx. Results: Patient backgrounds: Gender; M47/F27, Age; median 59(24-75), PS; 0or1=71/2=3, histological type; intestinal28/diffuse46, metastatic site; LN47/liver26/peritoneum29, CT per case; median number 4.5/ median interval 64.5days, endoscopy per case; median number 2/ median interval 91.3days. Response evaluation for gastric primary lesion between CT and endoscopy was compared in 141 examinations. Identical response 123(87.2%); both non-CR/non-PD 101/ both PD 22, not identical response 10(7.1%); endoscopy PD /CT non-CR/non-PD 10, not detected by CT; 8(5.7%). All of the cases of not identical response between CT and endoscopy were PD in endoscopy whereas non-CR/non-PD in CT. The overall response evaluation with or without endoscopy was concord in 133 evaluations (94.3%). Conclusions: It is almost appropriate that response evaluation of chemotherapy in AGC is mainly performed by CT without endoscopy to primary gastric lesion.
HapB3 and the deep intronic variant c.1129-5923 C>G of the dihydropyrimidine dehydrogenase gene (DPYD) to predict toxicity in stage III colon cancer (CC) patients (pts) (NCCTG Alliance N0147).
Authors: Lee Adam M , Shi Qian , Alberts Steven R. , Sargent Daniel J. , Sinicrope Frank A. , Berenberg Jeffrey L. , Goldberg Richard M. , Diasio Robert B.
Published: February 2017

508

Background: Severe adverse events (AEs) to 5-fluorouracil (5-FU) constitute a major dilemma in CC treatment. We recently demonstrated that specific deleterious DPYD variants in the coding region were highly predictive of grade >3 (G3+) AEs in stage III CC pts receiving adjuvant 5-FU based combination chemotherapy [Lee et al. JNCI. In press]. Other studies have suggested potential associations between AEs and non-coding DPYD variants: a novel haplotype (HapB3) containing three intronic variants (c.483+18 G>A, c.680+139 G>A, and c.959-51 T>C), one synonymous variant (c.1236 G>A, E412E), and a deep intronic variant (c.1129-5923 C>G) that affects pre-mRNA splicing. However, these studies included a diversity of cancer types, stages and treatments. The findings require further evaluation in a refined population. Methods: A total of 2,134 Caucasian stage III CC pts without DPYD*2A, D949V, and I560S variants from NCCTG N0147 trial who received adjuvant FOLFOX or FOLFIRI +/- cetuximab were genotyped by multiplexed single-base extension assays on the Sequenom MassARRAY. G3+ AEs were recorded (CTCAE v3) and classified as common to 5-FU treatment (5FU-AEs). Logistic regressions were used to assess the univariate and multivariate associations. Results: Analyzed pts displayed the following characteristics: 54.3% male, median age 59 [19-85], proficient MMR 87.5%, PS-0 76.5%, + irinotecan 8.5%, and + cetuximab 46.5%. Pts carrying c.1129-5923 C>G were significantly associated with higher risk of G3+ 5FU-AEs (Odds Ratio [OR]=1.539, 95% confidence interval [CI]=1.001 – 2.367, p=0.049). Only marginal association was observed for one of the HapB3 variants, c.1236 G>A (p=0.058). A linearly increasing risk of G3+ 5FU-AEs was identified for HapB3, comparing pts with no, one or >1 variant present (unadjusted OR=1.539, 95% CI=1.001 – 2.367, p=0.041; adjusted OR=1.198, 95% CI=0.998-1.437, p=0.052). Conclusions: In the largest study to date, c.1129-5923 C>G and HapB3 were predictive of 5FU-AE risk in stage III CC patients without DPYD*2A, D949V, and I560S variants receiving 5-FU-based combination chemotherapy.
Influence of adjuvant pretreatment on outcome of FIRE-3 (AIO KRK-0306): A randomized phase III study of FOLFIRI plus cetuximab or bevacizumab as first-line treatment for wild-type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC) patients.
Authors: Stintzing Sebastian , Modest Dominik Paul , Fischer von Weikersthal Ludwig , Decker Thomas , Kiani Alexander , Vehling-Kaiser Ursula , Al-Batran Salah-Eddin , Heintges Tobias , Lerchenmuller Christian A. , Kahl Christoph , Seipelt Gernot , Kullmann Frank , Stauch Martina , Scheithauer Werner , Held Swantje , Giessen Clemens Albrecht , Moehler Markus Hermann , Jung Andreas , Kirchner Thomas , Heinemann Volker
Published: February 2017

515

Background: The FIRE-3 study (AIO KRK-0306) was designed to compare the efficacy of FOLFIRI + cetuximab (cet) to FOLFIRI + bevacizumab (bev) as first-line treatment in KRAS WT mCRC patients. FOLFIRI plus cet resulted in comparable overall response rates (ORR) and progression free survival (PFS) when compared to FOLFIRI + bev. Overall survival (OS) was significantly longer in the FOLFIRI + cet arm. Methods: In an exploratory subgroup analysis, patients pretreated with adjuvant chemotherapy were analyzed by Fisher's exact and log rank-test according to tumor response (ORR) and survival data. Patients of the ITT (n=592) and the final RAS wild-type population (n=400) were investigated. Results: See table. Conclusions: Results in patients treated with any adjuvant chemotherapy mirrored those in the whole study population. In adjuvant pretreated RASwt patients a significantly higher ORR was reached in the cet arm when compared to the bev arm (p=0.01). The role of adjuvant treatment on efficacy of first-line therapy remains to be further evaluated. Clinical trial information: NCT00433927. [Table: see text] [Table: see text]
The diagnostic value of the immunochromatographic fecal tumor M2 pyruvate kinase test as a screening tool for colorectal malignant lesions.
Authors: Kim Jin Il , Kim Jae J.
Published: February 2017

517

Background: The M2 pyruvate kinase (M2-PK) is known as a specific enzyme produced in undifferentiated and proliferating tissues. However, the fecal tumor M2-PK ELISA test is expensive and time consuming, and also needs an available laboratory. For this reason, in the same way as immunochromatographic fecal occult blood test (iFOBT), an immunochromatographic fecal tumor M2-PK test (iM2-PK), has recently been developed. This is the study for the diagnostic value of the iM2-PK as a screening test for colorectal malignant and premalignant lesions. Methods: A total of 323 individuals participated. iFOBT and iM2-PK were performed with the stool samples. The participants consisted of 60 healthy volunteers, 124 patients with colonic adenoma, and 139 patients with colorectal cancer (CRC). The fecal tumor M2-PK ELISA tests were performed with the rest of stool samples from 68 participants, consisting of 40 patients with CRC, 26 patients with colonic adenoma, and 2 healthy volunteers. Results: For diagnosing CRC, the sensitivity, specificity, and area under the curve (AUC) were 92.8%, 83.3%, and 0.88 in iM2-PK, and 47.5%, 83.3%, and 0.65 in iFOBT. For diagnosing adenoma, the sensitivity, specificity, and AUC were 69.4%, 83.3%, and 0.76 in iM2-PK, and 12.1%, 83.3%, and 0.52% in iFOBT. The diagnostic accuracy of iM2-PK by using AUC was significantly higher than that of iFOBT for diagnosing CRC and adenoma (p< 0.05). In ELISA study, the sensitivity for CRC was 97.5% in iM2-PK, 47.5% in iFOBT, and 80.0% in fecal tumor M2-PK ELISA test. The sensitivity for adenoma was 69.2% in iM2-PK, 19.2% in iFOBT, and 61.5% in fecal tumor M2-PK ELISA test. The sensitivity of iM2-PK for diagnosing CRC was superior to that of iFOBT and M2-PK ELISA test (p< 0.05). Conclusions: iM2-PK is a rapid and cost-effective test for diagnosing CRC and colonic adenoma, and can easily performed in outpatient clinics. iM2-PK is a useful test in screening for CRC and colonic adenoma.
Prevalence of RAS mutations among patients with metastatic colorectal cancer by country and region in randomized clinical trials: A pooled analysis.
Authors: Peeters Marc , Kafatos George , Taylor Aliki , Gastanaga Victor M. , Yu Hua , Oliner Kelly Smith , Maglinte Gregory A. , Terwey Jan-Henrik , Krieken Han H. J. M.
Published: February 2017

520

Background: Global mCRC treatment guidelines for EGFR inhibitors require prior confirmation of wild-type RAS status (KRAS exons 2, 3, 4 and NRAS 2, 3, 4). The aim of this study was to estimate the prevalence of RAS mutations among mCRC patients by country, demographic characteristics, and clinical risk factors. A secondary aim was to estimate BRAF and KRASexon 2 mutation prevalence. Methods: Data from 5 published Amgen-sponsored randomized clinical trials (RCTs) were merged in a retrospective pooled analysis. There were 3 phase III, 1 phase II, and 1 phase Ib/II studies. For 4 out of 5 RCTs, RAStesting was conducted in a U.S. laboratory (Transgenomic Inc.) using Sanger sequencing on DNA extracted from tumor samples. For the remaining trial, a combination of next-generation sequencing and Sanger sequencing was used. Results: A total of 3,196 patients from 36 countries were included. The overall unadjusted prevalence of RAS mutations among mCRC subjects was 55.9% (95% CI, 53.9%, 57.9%); KRAS exon 2 mutation prevalence was 42.6% (40.7%, 44.5%). The prevalence by exon is given in the table below. BRAFmutation prevalence was 8.1% (6.7%, 9.6%). There were no statistically significant differences in RAS mutation prevalence by gender, age, or clinical factors such as performance status, tumour site, biopsy origin, or metastasis characteristics. Statistically significant differences in RAS mutation prevalence estimates were observed by country and by region with rates for Central West Europe being significantly lower than Eastern Europe (49.4% [44.4%, 54.3%] and 61.5%; [55.3%; 67.4%] respectively). Statistically significant RASmutation prevalence differences were observed between studies which could be due to varying patient characteristics. Conclusions: By merging data from RCTs, the analysis provides robust estimates of RASmutation prevalence. Studies using observational data are needed to confirm these findings. [Table: see text]
Temporal trends in colorectal cancer stage and presentation since the introduction of a national bowel screening program.
Authors: Mansouri David , Crearie Christine , Mcmillan Donald C. , Crighton Emilia M. , Horgan Paul G.
Published: February 2017

522

Background: Screening for colorectal cancer using the fecal occult blood test (FOBt) reduces cancer specific mortality through the detection of early stage disease. However, population screening programs are limited by both uptake and the sensitivity of the test. The present study aimed to examine the effect of a national screening program on TNM stage and presentation in our geographical region. Methods: A biennial FOBt screening program, inviting all males and females aged 50 to 74 years, was introduced in 2007 in a stepwise manner across the region with full coverage achieved by 2011. Regional cancer audit databases and national population statistics were examined to compare Early screening introduction (2007/8), Late screening introduction (2009/10) and Post screening (2011/12) time periods. Results: In a population of 2.4 million, over a 6 year period, 9,723 patients were diagnosed with colorectal cancer (3098 Early; 3282 Late; 3343 Post). There was a small overall increase in incidence during the study period (0.064%/year Early vs 0.068%/year Post, p=0.017). This increase remained when adjusting for sex in both males and females. There was no difference in the age, sex or socioeconomic deprivation status of patients across the three time periods. The proportion of screen-detected cancers increased over time (3% Early vs 18% Post, p<0.001) with a concomitant fall in elective symptomatic presentations (62% Early vs 47% Post, p<0.001). No difference in the proportion of emergency presentations was seen (13% Early vs 13% Post, p=0.282). There was no difference in tumor site (p=0.692) or overall TNM stage at diagnosis (p=0.548) over time. However, when those presenting with non-metastatic disease were examined separately, there was clear trend towards earlier stage disease (18% Stage 1 Early vs 28% Stage 1 Late, p<0.001). Conclusions: Despite only accounting directly for a limited proportion of all tumors detected, the introduction of a national screening program has been accompanied by a stage shift in colorectal cancer disease towards earlier presentation. Further work is required to target those more likely to present as an emergency as they appear resistant to the current program.
Ziv-aflibercept (Z) in combination with FOLFIRI for second-line treatment of patients (pts) with metastatic colorectal cancer (mCRC): Interim safety data from the global Aflibercept Safety and Quality-of-Life Program in pts pretreated with bevacizumab (B).
Authors: Sobrero Alberto F. , Bordonaro Roberto , Bencardino Katia , Pietrantonio Filippo , Bauer Stefan , Taïeb Julien , Garreau-Laporte Pascale , Zilocchi Chiara , Dochy Emmanuelle , Lledo Gérard
Published: February 2017

528

Background: In the VELOUR study, adding ziv-aflibercept (Z) (known as aflibercept outside the United States) to FOLFIRI resulted in improved OS, PFS, and RR in metastatic colorectal cancer (mCRC) patients (pts) who had received prior oxaliplatin. Prior treatment with bevacizumab (B) did not appear to impact safety profile of Z. The global ASQoP/AFEQT studies are 2 clinical studies (ASQoP [NCT01571284]; AFEQT [NCT01670721]) designed to capture QoL and safety data from a population similar to VELOUR but treated in a real-life setting. We report safety data from the 4th interim analysis in B-pretreated pts. Methods: ASQoP/AFEQT are single-arm, open-label trials of Z in mCRC pts previously treated with an oxaliplatin-containing regimen. Eligible pts receive Z (4 mg/kg) q2w on day 1 of each cycle followed by FOLFIRI until disease progression, unacceptable toxicity, death, or investigator/pt decision. Initial starting doses of FOLFIRI and subsequent modifications are at treating physician’s discretion. % of pts with grade (G) 3 or 4 AEs in the combined B-pretreated safety population of ASQoP/AFEQT is compared with B-pretreated pts in the Z + FOLFIRI arm of VELOUR. Results: At data cutoff, overall safety population comprised 688 pts with ≥1 completed treatment cycle; 343 (49.9%) were B-pretreated. Currently, median number of cycles administered to ASQoP/AFEQT pts is 6; in VELOUR, pts in Z + FOLFIRI arm had a median of 9. Table shows summary of TEAEs in B-pretreated pts. Conclusions: Thisinterim safety analysis of ASQoP/AFEQT in B-pretreated pts identified no new safety signals for Z and a trend toward decreased G3/4 events. The analysis provides additional safety data suggesting an acceptable toxicity profile in a real-life setting. Clinical trial information: NCT01571284. [Table: see text]
The impact of hepatic fiblosis on the incidence of liver metastasis from colorectal cancer.
Authors: Kondo Takayuki , Okabayashi Koji , Hasegawa Hirotoshi , Tsuruta Masashi , Seishima Ryo , Matsui Shimpei , Yamada Toru , Takahashi Hidena , Shimada Takehiro , Matsuda Mutsuhito , Yahagi Masashi , Yoshikawa Yusuke , Asada Yusuke , Sugiura Kiyoaki , Suzuki Yoshiyuki , Tajima Yuki , Nakadai Junpei , Kitagawa Yuko
Published: February 2017

529

Background: Non-alcoholic steatohepatitis (NASH) is closely associated with hepatic fibrosis (HF). The number of patients who have NASH is increasing by eating high-calorie diet. It remains unclear how much impact such NASH and HF on the development of liver metastasis by colorectal cancer (CRC). The objectives of this study is to clarify the influence of HF on metachronous liver-specific recurrence in colorectal cancer patients who underwent colorectal surgery with curative intent. Methods: Between 2000 and 2010, patients who underwent a curative surgical resection for CRC were included in this study. We evaluated the progression of HF by using non-alcoholic fatty liver disease fibrosis score (NFS) based on preoperative blood test result, age, BMI and DM. The patients with NFS higher than 0.676 were objectively defined as HF. The influence of HF on hepatic recurrence was assessed by survival analyses. Results: A total of 953 CRC patients were enrolled, comprised of 293 in stage I, 327 in stage II and 333 in stage III. The mean of NFS was 1.32±1.55, where the included patients were categorized into 77 HF and 876 non-HF. 5-year liver-specific disease-free survival rate in HF was significantly poorer than non-HF (HS 87.0% vs. non-HF 94.5%, log-rank p=0.009). Multivariate analysis demonstrated that HF significantly promoted liver-specific recurrence compared to non-HF (HR=2.16, 95% CI, 1.00 to 4.64; p=0.049). Conclusions: Hepatic fibrosis had a great impact on hepatic recurrence after curative surgical resection of CRCs. These findings indicated that HF might be a favorable microenvironment in developing colorectal liver metastasis. The evaluation of the degree of HF can be useful in selection of adjuvant chemotherapy and postoperative surveillance.
Effect of arecoline, the major alkaloid of areca nut, on the number of N-benzyl-N-methylnitrosamine (NMBA)-induced esophageal papilloma in F344 male rats.
Authors: Wu Ming-Tsang
Published: February 2017

53

Background: Arecoline is the major alkaloid of areca nut which is one major risk of developing esophageal squamous cell carcinoma (ESCC) in the Asian population. This study aims to establish one rat model to study the relationship of areca nut exposure with the development of ESCC. Methods: Six-week-old Fischer 344 male rats were injected subcutaneously with 0.5 mg/kg NMBA thrice a week for the first 5 weeks and given water without or with arecoline (500 mg/ml) for 30 weeks. Results: With co-treatment of arecoline, NMBA-injected rats had significantly more esophageal papillomas (p = 0.02) and marginally significantly more tongue papillomas (p= 0.09) per rat, compared to those with NMBA only in the end of week 30. No papilloma was found in the lung, liver and/or stomach among all experimental groups. The histological features of esophageal papilloma showed the hyperplastic changes of squamous epithelium. Conclusions: This established animal model can be ideally used to study areca nut-associated esophageal carcinogenesis.