bluuebunny/crossref_metadata_2025_split huggingface dataset:
MAVERICC, a phase 2 study of mFOLFOX6-bevacizumab (BV) vs FOLFIRI-BV with biomarker stratification as first-line (1L) chemotherapy (CT) in patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Lenz Heinz-Josef , Lee Fa-Chyi , Yau Linda , Koh Han A. , Knost James A. , Mitchell Edith P. , Bosanac Ivan , Mancao Christoph , Parikh Aparna 
Published: February 2017

493 Background: Standard 1L mCRC treatment (tx) includes a CT backbone (e.g., modified leucovorin [LV]/5-fluorouracil [5-FU]/oxaliplatin [mFOLFOX6] or LV/ 5-FU/ irinotecan [FOLFIRI]) and biologic therapy (e.g., BV). The preferred CT backbone for anti VEGF tx is unknown. MAVERICC (NCT01374425), a global, randomized, open-label, phase 2 trial, assessed tx efficacy and safety of mFOLFOX6-BV vs FOLFIRI-BV in pts with mCRC. Intratumoral ERCC1 and plasma VEGF-A were studied as biomarkers for oxaliplatin- and BV-containing tx, respectively. Methods: Pts with mCRC (≥1 measurable metastatic lesion, ECOG performance status ≤1) were randomized 1:1 to receive BV (5 mg/kg) + mFOLFOX6 or FOLFIRI every 2 weeks, stratified by ERCC1 level (low [£1.7] vs high [>1.7]) and region. VEGF-A levels were measured at baseline. Primary objectives were to evaluate: ERCC1 as a biomarker of progression-free survival (PFS) in 1L mCRC tx (mFOLFOX-BV vs FOLFIRI); and VEGF-A as a biomarker for BV and as a biomarker in combination with ERCC1 for PFS following CT + BV. Secondary objectives were to evaluate: the effect of ERCC1 and VEGF-A on overall survival (OS), objective response rate, hepatic metastases resection, and safety. PFS and OS were estimated by Kaplan–Meier methods, hazard ratios (HR) were estimated by Cox regression, and p-values were based on stratified log-rank tests. ERCC1 biomarker analyses are presented here. Results: A total of 376 pts were randomized: median age, 61 yr; white race, 83%; US region, 85%. Baseline characteristics: ERCC1 high, 35%; KRAS mutant, 34%. Efficacy results are shown (see Table). Conclusion: Consistent with previous findings, PFS and OS were comparable in pts treated with either 1L mFOLFOX6-BV or FOLFIRI-BV. Exploratory analyses within pts with high ERCC1 levels suggest consistent results. VEGF-A analyses are ongoing. Clinical trial information: NCT01374425. [Table: see text] [Table: see text]
A phase II therapeutic, open label, multi-center clinical trial of NPC-1C, a chimeric monoclonal antibody(mAb), in adults with chemotherapy refractory metastatic colorectal cancer (mCRC), initial results.
Authors: Kim Richard D. , Azad Nilofer Saba , Morse Michael , Tan Benjamin R. , Poplin Elizabeth , Beatson Melony A. , Mavroukakis Sharon , Arlen Philip M. , Beg Muhammad Shaalan 
Published: February 2017

500 Background: NEO-102 is a novel chimeric mAb targeting a variant of MUC5AC with specificity to colorectal cancer. Its mechanism of action is through antibody dependent cellular cytotoxicity (ADCC). An earlier, phase I study, established the maximum tolerated dose at 3.0 mg/kg IV every 2 weeks with encouraging early signs of clinical activity. We report initial results of the subsequent phase II study. Methods: This is a single arm, open label multi-center clinical trial of NEO-102 in adults with mCRC pts who failed at least two lines of standard chemotherapy (C). An immunohistochemistry (IHC) based companion diagnostic assay was used to select eligible pts whose tumors express the target in > 20% of tumor cells. NEO-102 at 3.0 mg/kg IV was administered q 2 weeks until disease progression. The primary endpoint was OS. A minimum of 43 pts were needed assuming that treatment with NEO-102 will improve OS by 40% (7.0 months) using a one-sided significance level of 10% and 80% power for this study compared to historical control of 5 months. Additional objectives were to evaluate response rate as measured by RECIST criteria and analyze patient PBMCs for ADCC and immune cytokine profiling. Results: A total of 47 pts enrolled were evaluable. 26 pts were male and 35 pts were white. Twenty-four out of 47 pts (51%) remain alive as of September 2015 with an ongoing median OS of 7.0 months (Range 2-22 months). Of these heavily pre-treated pts, 42 were evaluable for response, 13 (31%) demonstrated stable disease by RECIST. Seven pts had more than 4 doses of treatment, maximum 13 doses. Grade 3 adverse events were anemia 1/47 (2%), hyperbilirubinemia 1/47 (2%), diarrhea 1/47 (2%), fatigue 1/47 (2%), headache 1/47 (2%), nausea 1/47 (2%) and vomiting 1/47 (2%). No grade 4 toxicities were reported. Conclusions: In the monotherapy phase 2 study of NEO 102 in patients with refractory mCRC preliminary results demonstrate excellent tolerability and encouraging OS. Updated OS and Progression Free Survival data will be presented at the ASCO 2016 GI Cancers symposium. Additional combination trials with NEO-102 and C are underway. Clinical trial information: NCT01040000.
Assessing solid tumor response with and without RECIST.
Authors: Deng Aileen , Leiby Benjamin E , Schilder Russell J. , Kelly William Kevin , Deshmukh Sandeep , Sama Ashwin Reddy 
Published: February 2017

504 Background: Response Evaluation Criteria in Solid Tumors (RECIST) has become widely accepted as gold standard for response evaluation in clinical trials. It remains underutilized in routine clinical practice. We compared tumor response assessment made with and without RECIST. Methods: This study included patients with solid tumors who underwent imaging from January 2013 to December 2014 at a single academic center. Tumor response was assessed by a radiologist using RECIST and by an oncologist (Onc) and resident (Res) without using RECIST (standard report). Tumor response was classified as progressive disease (PD), stable disease (SD), partial response (PR) and complete response (CR). Agreement in assessment between RECIST and standard report was determined by percent agreement and Kappa statistic. Results: 292 imaging studies were included. Concordance between RECIST and Onc-interpreted standard report is presented in Table 1. Overall agreement between RECIST and Onc-interpreted standard report was 56% (95% CI: 46-65%) and Kappa was 0.31 (95% CI: 0.19-0.44). Similar results were seen between RECIST and Res-interpreted standard report (Table 1). Overall agreement between RECIST and Res-interpreted report was 54% (95% CI: 44%-63%) and Kappa was 0.26 (95% CI: 0.13-0.40). Conclusions: Our study found variability in tumor response assessment between clinicians and radiologists. RECIST-classified PD was often interpreted as SD and vice versa, a distinction that affect treatment decisions. Our study highlights the need to standardize tumor response assessment. [Table: see text]
Correlation of pretreatment p63-positive subtype of gastroesophageal adenocarcinoma (GEAC) with pathologic complete response (pathCR) in patients receiving preoperative chemoradiation.
Authors: Elimova Elena , Kim Soo-Mi , Wang Xuemei , Shimodaira Yusuke , Sohn Bo Hwa , Skinner Heath Devin , Lee Jeffrey H. , Weston Brian , Bhutani Manoop S. , Minsky Bruce D. , Rice David C. , Hwang Jun Eul , Swisher Stephen , Hofstetter Wayne Lewis , Blum Mariela A. , Maru Dipen M. , Ajani Jaffer A. , Lee Ju-Seog 
Published: February 2017

51 Background: Biomarker or biomarker signature(s) is needed to help optimize therapy of GEAC patients undergoing multimodality therapy. p63 is a transcription factor important in the development of squamous epithelial lineage and mediating ectodermal-mesenchymal interactions. Methods: Primary objective of this study was to study the predictive value of p63-associated subtype for pathCR. Other outcomes were also studied. Results: Unsupervised cluster analysis of gene expression data from 185 GEAC patients uncovered two distinct subtypes of GEAC with differences in expression of p63 mRNA: p63-positive and p63-negative. All patients had chemoradiation and surgery. Most were men (88%), all had adenocarcinoma, and most were p63-negative (69%). 25% of patients achieved a pathCR. The median follow-up for all patients was 3.9 years (range, 0.1 – 11.5). p63-positive subtype was associated with pathCR in both a univariate and multivariate analyses (p = 0.04 and p = 0.02, respectively). Female patients with p63-positive subtype, lower no. of ypNodes, and low grade GEACs had a higher probability of pathCR. However, p63-positive subtype was not prognostic (PFS, p = 0.26 or OS, p = 0.80). The median OS for all patients was 4.8 years (95% CI, 3.3 – 6.7 years). Higher no. of ypNodes, higher histologic grade, and mid- or higher esophageal primary were associated with shorter OS (with p-values of < 0.0001, 0.0004 and 0.0001, respectively). Conclusions: Our data suggest that pretreatment p63-positive subtype of GEAC highly correlates with pathCR. Further refinement/validation and combination with other biomarkers is warranted.
Is the accuracy of preoperative MRI stage in rectal carcinoma influenced by tumor height?
Authors: Poulsen Laurids Østergaard , Yilmaz Mette K. N. , Oddershede Lars , Bøgsted Martin , Holt Gitte , Eld Mikkel , Ljungmann Ken , Falkmer Ursula 
Published: February 2017

514 Background: In order to select patients with adenocarcinoma of the rectum (RC) for optimal treatment strategies, there is a need for accurate staging of the neoplastic disease. Here, magnetic resonance imaging (MRI) is considered to be the gold standard. However, some concerns have been raised about the reproducibility of earlier results. Newer treatment strategies which include organ saving in RC patients will further emphasize the need. The aim of the present study was to evaluate the degree of accuracy of the MRI staging. Methods: All patients diagnosed with RC in northern Denmark 2009-2013 (n = 1017) were screened for inclusion. All MRI were performed on 1.5 T MRI scanners and the evaluations were made by in all four expert GI-radiologists. Only patients who were offered surgery without preoperative treatment were included (n = 357). The result of the preoperative MRI staging was correlated to the postoperative histopathological stage. Results: There were 56, 131 and 190 patients respectively with low- (0-5 cm from the anal verge), mid- (5-10 cm) and high RC (10-15 cm). MRI T-staging was in accordance with the histopathology in 84 % of the cases (81% for low, 86% for mid, and 83% for high tumors, respectively) and the accuracy was not affected by tumor height. The results were consistent over time. Concerning the MRI staging of nodal-involvement, there was a sensitivity of 88% and a specificity of 30%. Data regarding tumor invasion and distance from the tumor to mesorectal fascia will be presented at the meeting. Conclusions: MRI T-stage correlated well with postoperative histopathological T-stage, whereas the correlation to nodal involvement was poor and in accordance with previous results.
Changes in non-invasive liver fibrosis indices during chemotherapy: Potential marker for oxaliplatin-induced sinusoidal obstruction syndrome.
Authors: Kim Jin-Soo , Park Sehhoon , Kim Ki Hwan , Park Jin Hyun , Kim Won , Choi In Sil , Jung Yong Jin , Kim Hwi Young 
Published: February 2017

515 Background: Oxaliplatin-based regimens are standard treatments for patients with colorectal (CRC) and advanced gastric cancer (AGC). However, the use of oxaliplatin sometimes results in hepatic sinusoidal obstruction syndrome (SOS). The aim of the study was to evaluate the utility of non-invasive liver fibrosis indices for monitoring oxaliplatin-induced hepatic SOS. We have reported a preliminary data in ASCO Annual Meeting 2014. Methods: From February 2004 to April 2014, patients with CRC or AGC who received oxaliplatin-based chemotherapy were studied. Possibility of SOS development was evaluated before and after the oxaliplatin exposure with splenic volume index (SVI). Four different non-invasive liver fibrosis indices were used for risk analysis: age-platelet index (API), AST to platelet ratio index (APRI), platelet to spleen ratio (PSR), Fibrosis-4 score (FIB-4). A prospective observation with serial elastrography is also ongoing. Results: A total of 275 patients were eligible for evaluation: 200 patients had CRC, and 75 patients had AGC. Using a cutoff of SVI increase ≥ 0.3, 113 patients (41.1%) were positive for hepatic SOS. Changes of indices were significantly correlated with SVI increase. Adjusted odds ratios for those indices were as follows: API = 1.16 (95% Confidential Interval [CI], 1.01 - 1.32; P = 0.032); APRI = 2.45 (95% CI, 1.30 - 4.63; P = 0.006); PSR = 0.69 (95% CI, 0.59 - 0.80; P < 0.001); FIB-4 = 1.37 (95% CI, 1.16 - 1.63; P < 0.001). Optimal cutoff-value with statistical significance were calculated and suggested. A total of 20 patients have been enrolled into the prospective observation until now. Comparison of elastographic changes and the indices in these patients will be presented. Conclusions: Changes of non-invasive liver fibrosis indices showed good correlation with SVI increase during oxaliplatin-based chemotherapy. These indices might be useful markers for monitoring of oxaliplatin-induced hepatic SOS. Serial monitoring of hepatic elastography could also be used for non-invasive monitoring of hepatic SOS.
Epidemiology and survival of small cell carcinoma of gastrointestional tract: A Surveillance, Epidemiology, and End Results (SEER) database review.
Authors: Kumar Abhijeet , Sundararajan Srinath , Cui Haiyan , Patel Hitendra , Elquza Emad 
Published: February 2017

518 Background: Small cell carcinoma of the gastrointestinal tract is an uncommon histology. Limited literature is available to clinicians about the incidence, distribution and prognosis of small cell carcinoma of the gastrointestinal tract (SCGIT). We reviewed the Survival, Epidemiology and End Result (SEER) database of National Cancer Institute to understand its epidemiology and prognosis. Methods: SEER database was reviewed for patients with histologically confirmed SCGIT (8041-45) and its variants in the GIT between 2002-2007 (all stages). Variables included were age, gender, race, primary site and disease specific survival. The incidence pattern across race, gender, and site of origin for SCGIT was investigated. Chi square test was used to assess the difference of incidence pattern. 5-yr survival rate across various sites was estimated using the Kaplan–Meier method and the difference in 5-yr survival was tested by log-rank test. If the significant difference is detected, the paired comparison was performed and the p-values were adjusted by Tukey multiple-comparison method. Results: A total of 645 patients were included. The distribution of SCGIT was: colorectal (30.08%), esophagus (22.17%), pancreas (20.16%), hepatobiliary (11.63%), stomach (9.61%) and NOS (6.63%). The incidence pattern of SCGIT in males and female was significantly different (p < 0.0008). Males had a higher incidence of esophagus; stomach and pancreas while females had a higher incidence of hepatobiliary, colorectal and NOS sites. Five-year survival of SCGIT was significantly associated with the primary site of disease (p = 0.03). Paired-comparison results showed that the 5-yr survival rate for patients with pancreas small cell cancer was significantly lower than patients with stomach or NOS(4.80% -pancreas vs 5.22 %-stomach and 12.81% - NOS) (p = 0.04 and p = 0.003 respectively). There was not a significant difference between other sites. Conclusions: Small cell carcinoma of the GI tract has difference in incidence patterns between genders. The 5-yr survival of patients with pancreatic small cell carcinoma is significantly lower as compared to stomach or NOS.
Case review for ramucirumab as a single agent in our hospital.
Authors: Murahashi Satoshi , Takahari Daisuke 
Published: February 2017

52 Background: Ramucirumab is approved in the USA, EU, and Japan as second-line treatment in advanced gastric or gastroesophageal junction adenocarcinoma. This agent is often used with paclitaxel, but we can use it as a single agent in second-line treatment. Because REGARD trial has shown that Ramucirumab as a single agent prolongs overall survival and progression-free survival. However, this trial doesn’t include Japanese patients, and we have no trial concerning the efficacy of Ramucirumab as third or later-line treatment up to date. We reviewed retrospectively the efficacy and safety of Ramucirumab as a single agent in our hospital. Methods: We investigated 12 cases from June (when Ramucirumab has been approved) to September. Results: The median age was 61 years old, 6 male and 6 female patients. Performance status (0/1/2) = (1/10/1) cases. (second/third/fourth or later)-lines = (4/4/4) cases. Metastatic sites are lymph node, liver, lung, bone, and peritoneum. 7 patients had gastrectomy and 5 patients of them received adjuvant chemotherapy. Response rate is 50%, median progressive-free survival is 51 days, and median overall survival is 13 months. Some patients experienced grade 1or 2 adverse events: fatigue, loss of appetite, diarrhea, and hypertension. Conclusions: We cannot say that single agent administration of Ramucirumab demonstrates good response, some patients kept stable disease in this regimen. Ramucirumab as a single agent can be an option of treatments after paclitaxel fails or when it is difficult to administrate it.
The novel diagnostic method for colorectal cancer: Detection of methyl mercaptan from flatus.
Authors: Ishibe Atsushi , Ota Mitsuyoshi , Tsuboi Hiroshi , Takeshita Akemi , Suwa Yusuke , Suzuki Shinsuke , Suwa Hirokazu , Momiyama Masashi , Watanabe Jun , Kosaka Takashi , Watanabe Kazuteru , Akiyama Hirotoshi , Ichikawa Yasushi , Kunisaki Chikara , Endo Itaru 
Published: February 2017

529 Background: Fecal occult blood test screening for colorectal cancer (CRC) reduces cancer specific mortality through the detection of early stage disease. However, medical examination rate is very low in Japan because of the inconvenience of sampling of stool. On the other hand, it is reported that dogs can be trained to distinguish breath samples of patients with lung and breast cancer from those of control. It is unclear that odour materials become effective tools in CRC screening. The aims of this study were to evaluate the gas components in the flatus of CRC patients and to compare with healthy controls. Methods: Thirty-two patient before elective colorectal surgery in Yokohama City University and 13 healthy controls were enrolled in this study.The apparatus for gas sampling was placed in the toilet. Defecation gas from a patient in a toilet stool was collected in a 25L sampling bag. A fan (50 L / min ) was arranged to aspirate air in the toilet stool. Defecation gas components were collected as follows: (1) Air in the toilet stool was aspirated with the fan and passed through a commercial gas sensor. (2) Gas sampling started after the gas sensor detecting gas components.Volatile sulfur-containing compounds in sampling bag were injected into the gas chromatography by Entech pre-concentrator and analyzed. Results: The amount of methyl mercaptan was significant higher compared with control. Methyl mercaptan and hydrogen sulfide were related to tumor size (r = 0.415，p = 0.018, r = 0.454，p = 0.009). Methyl mercaptan tended to increase as the stage advances (p = 0.022）．Based on an optimal cut-off value calculated by ROC curve analysis had accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 68.9%, 68.8%, 69.2%, 84.6%and 47.3%, respectively, for the diagnosis of CRC. Conclusions: The methyl mercaptan from the toilet stool during defecation was increasing in CRC patients. Measurements of methyl mercaptan suggests possibility of more easily and precise colorectal cancer screening.
Lynch Syndrome diagnosis in Ireland: The impact of universal mismatch repair protein testing.
Authors: Corrigan Lynda , Clabby Catherine , Green Andrew J. , Barton David , Gallagher David James 
Published: February 2017

532 Background: It is estimated that approximately 2-4% of colorectal cancers (CRCs) are attributable to Lynch Syndrome (LS). Immunohistochemical testing for mismatch repair proteins is increasingly being performed on CRC specimens. In some centres all incident cases undergo this testing. An abnormal result should initiate a cascade of testing to determine if the loss of mismatch repair protein expression is sporadic or hereditary. We examined the pattern of cancer genetics referral for hereditary CRC diagnosed in Ireland under the age of 70 years. Methods: The number of patients with CRC diagnosed under the age of 70 between 2005 and 2013 was obtained from the National Cancer Registry of Ireland. The number of patients referred for cancer genetics work-up with a diagnosis of CRC < 70 years of age was ascertained from the Department of Clinical Genetics, Our Lady’s Hospital, Crumlin (DCG), the only genetics laboratory in Ireland which processes such samples. The database of the DCG was searched for referrals for hereditary CRC syndromes; and the clinical reason for referral recorded. Results: Between 2005 and 2013, 10,334 patients were diagnosed with CRC less than 70 years of age. 85% were between 50 and 69 years of age (n = 8,736). 229 people under the age of 70 years were referred for cancer genetics work-up for LS with a diagnosis of CRC. Those referred for a non-CRC LS phenotypic manifestation and for predictive testing were excluded. For 41 individuals the reason for referral was not specified. Individuals with CRC were referred for one of the following reasons: diagnosis of CRC < 70 years in 76 patients (33%), diagnosis of CRC < 70 with a family history of LS-associated malignancy in 137 patients (60%), and diagnosis of CRC < 70 with known familial genetic mutation in 16 patients (7%).This represents a referral rate of approximately 0.02% for CRC diagnosed under 70 years of age. Conclusions: 0.2% of colorectal cancer cases diagnosed at < 70 years of age in Ireland over a nine year period were referred for cancer genetics opinion. Increased immunohistochemical testing for mismatch repair proteins should result in increased cancer genetics referral, which will require appropriate service provision within oncology management pathways.