bluuebunny/crossref_metadata_2025_split huggingface dataset:
A clinical parameters-based predictive model to predict early efficacy for rectal cancer patients with neoadjuvant chemotherapy alone: Subgroup efficacy analysis of a phase II study.
Authors: Zhang Jianwei , Cai Yue , Hu Huabin , Lan Ping , Wang Jianping , Huang Meijin , Kang Liang , Deng Yanhong 
Published: February 2017

716 Background: To avoid the damage of radiotherapy for a part of patients, we have an ongoing phase II study comparing Neoadjuvant FOLFOX6 chemotherapy with or without radiation in Rectal Cancer. To define the population who could obtain benefit from neoadjuvant chemotherapy alone, we aimed to develop a model in which clinical parameters are used to predict early efficacy of neoadjuvant chemotherapy for rectal cancer, including tumor regression grade (TRG) and ypTNM down-staging. Methods: Until now, 116 patients were enrolled into FOLFOX6 chemotherapy alone group. All the clinical parameters were collected, including gender, age, tumor location and size by MRI imaging, blood routine test, blood biochemistry and serum tumor markers, TRG and ypTNM staging. 96 patients were used to be training set and another 20 patients was the validation set. Binary logistic regression was used to analyze the effect of all clinical factors on TRG and ypTNM stage. Clinical variables were incorporated into the Cox models for multivariate analysis. Results: Among the 116 patients, 9 patients had TRG 0 (complete regression), 26 patients with TRG 1 and 81 patients with TRG 2 to 3 (poor regression). 47 (40.5%) patients had good down-staging with ypTNM stage 0 and stage I. The optimal multivariable predictive model for TRG (0-1 vs. 2-3) was a four-variable model consisting of age, ApoA1, tumor length and tumor encircle size (AUC=0.732, 95% CI, 0.614–0.849). The model for ypTNM (stage 0-I vs. II-III) was also the four parameters (AUC=0.725, 95% CI, 0.615–0.835). Patients with younger age, shorter tumor length, smaller encircle size and higher ApoA1 had better outcome with chemotherapy. Applying the four clinical parameters model to the validation cohort, a good performance (AUC=0.792, 95% CI, 50.54–0.95) was obtained. Conclusions: With this predictive model, the patients who might obtain good efficacy from neoadjuvant FOLFOX6 chemotherapy could avoid radiotherapy damage. And better suggestion would be provided for patients who might be high risk with chemotherapy alone.
Clinical significance of cellular and acellular mucin pools in rectal carcinoma following preoperative chemoradiotherapy.
Authors: Cienfuegos Javier A. , Rotellar Fernando , Baixauli Jorge , Sola Iosu , Arredondo Jorge , Pastor Carlos , Hernandez-Lizoain Jose Luis 
Published: February 2017

718 Background: Currently, the standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (CRT) followed by surgery. Pathological findings in post-treated specimens remain the most significant prognostic factor. The presence of mucin pools and their prognostic significance is a controversial issue. Methods: The aim of this study was to analyze the incidence of cellular and acellular mucin pools and their clinical significance in 446 consecutive prospectively collected specimens from patients with stages II/III treated with preoperative CRT and surgery. Results: Mucin pools were present in 182 specimens (40.8%); 66 (14.7%) were acellular, and viable tumor cells were identified in 116 (26.0%). If acellular mucin is considered as a type of response and not residual tumor, the complete pathological response rate was 12.8% (57 of 446). With a median follow-up of 79.0 months, the 5- and 10-year disease-free survivals for patients with acellular and cellular mucin pools, were 81.8% and 63.4%, respectively (p < 0.0225). The presence of cells in the colloid response to treatment was associated with a 2.5-fold increase in the possibility of dying of rectal cancer (HR = 2.5 [1.1 − 5.76], p= 0.028 univariant Cox regression analysis). Conclusions: Thus, our results suggest that cellular mucin pools are an indicator of an aggressive phenotype and harbingers of a worse prognosis.
DEBIRI and capecitabine in refractory prevalently liver metastases of colorectal cancer: A phase II study.
Authors: Marsico Valentina Angela , Orlandi Armando , Cerchiaro Eleonora , Iezzi Roberto , Di Noia Vincenzo , Mannavola Francesco , Calegari Maria Alessandra , Corallo Salvatore , Cassano Alessandra , Barone Carlo 
Published: February 2017

724 Background: Treatment options for metastatic colorectal cancer (mCRC) patients refractory to chemotherapy are limited and clinical outcome is poor. In mCRC patients with liver-dominant disease hepatic locoregional therapy might be a treatment option. In this pilot study we evaluated the safety, tolerance, and efficacy of drug-eluting beads irinotecan (DEBIRI) in combination with capecitabine in the treatment of patients with mCRC with predominally liver disease. Methods: Twenty patients affected by liver metastasis of colorectal cancer were included in this study. All patients had progression of disease after two or more lines of chemotherapy and liver was the major or the predominant site of disease. DEBIRI, beads loaded with 100 mg irinotecan, was administered biweekly via hepatic artery. All patients assumed capecitabine 1,000 mg/m2 twice daily on days 1 to 14 every 3 weeks, until disease progression. Primary endpoints were safety, tolerance and overall responce rate (ORR); secondary endpoints were progression free servival (PFS) and overall survival (OS). Results: Twenty patients underwent a total of 54 DEBIRI treatments of the 66 planned; the median number was 3 (range 2-4) administrated for patients. Grade 1-2 toxic effects included fatigue (70%), diarrhea (45 %), anemia (45%), elevated liver enzymes (45%), nausea (40%), neutropenia (35%) and thrombocytopenia (25%). One grade 3 diarrhea and a case of acute vasospastic angina were observed and required patient hospitalization, but no deaths at 30 days post occurred. Two partial responses were reported (10%) with ORR of 60%. PFS and OS were 4 and 7, 3 months respectively. Univariate analysis showed that patients with KRAS wild-type, good ECOG performance status and single lobe metastases have a better prognosis. Multivariate analysis confirmed that only the good clinical conditions represent an important positive prognostic factor (p=0.03). Conclusions: DEBIRI with capecitabine seem to be a safe, technically feasible and well-tolerated treatment in chemotherapy refractory mCRC with prevalently liver metastases. It has a moderate but not negligible activity in this heavily treated group of patients and deserves further studies in a larger series.
A validation study of preventing oxaliplatin-induced hypersensitivity reactions by dexamethasone: The AVOID trial.
Authors: Hirata Keiji , Yoshida Yoichiro , Matsuoka HIroshi , Iwamoto Shigeyoshi , Kotaka Masahito , Fujita Hideto , Aisu Naoya , Hoshino Seiichiro , Kosaka Takeo , Maeda Kotaro , Yamashita Yuichi 
Published: February 2017

727 Background: Patients treated with oxaliplatin are at risk for hypersensitivity reactions. The incidence of hypersensitivity reactions in clinical practice is estimated to be 12% to 20%. Prescribing information says that oxaliplatin is incompatible in solution with alkaline medications or media and must not be mixed these or administered simultaneously through the same infusion line. Because steroid is alkaline, the coinfusion of steroids and oxaliplatin can make oxaliplatin unstable due to the elevation of pH; further, the effectiveness of steroid in this therapy is unknown. Therefore, dexamethasone is routinely given to patients before they receive chemotherapy. However, we have reported that the pH after the addition of DEX (6.6 mg) to oxaliplatin was less than 7.4, and there is possibility that hypersensitivity reactions to oxaliplatin could have been prevented by coinfusion of dexamethasone (DEX) (Yoshida et al.2012 ASCO-GI) but just in a retrospective study. This prospective study was undertaken to evaluate the effectiveness of coinfusion of DEX to oxaliplatin for controlling hypersensitivity reactions caused by oxaliplatin. Methods: The AVOID trial is a prospective, multicenter, open-label, single-arm, phase II trial investigating hypersensitivity reactions to oxaliplatin could have been prevented by coinfusion of DEX. The study included 73 patients who received XELOX or XELOX +bevacizumab therapy for colorectal cancer. In all the patients, oxaliplatin (130mg/m²) was administered in combination with DEX (6.6 mg). Results: Hypersensitivity reactions developed in 3 patients (4.1%). Respiratory symptoms, ocular symptoms and anaphylaxis were not observed in 73 patients. The three patients experienced cutaneous reaction (erythema: grade1). Grade 3 or higher hemotoxicity was noted in 13.7% of the patients, and grade 3 or higher nonhematological toxicity was noted in 13.7%. The response rate was 58.1%. Conclusions: This trial supports coinfusion of dexamethasone and oxaliplatin reduced oxaliplatin-related hypersensitivity reactions. This effective approach should be considered for all patients who receive oxaliplatin, allowing treatment to be completed as planned. Clinical trial information: UMIN000009742.
A multi-institutional feasibility study of S-1/oxaliplatin (SOX) plus bevacizumab in patients with advanced/metastatic colorectal cancer: HiSCO-02 prospective phase II study.
Authors: Kurayoshi Manabu , Shinozaki Katsunori , Hinoi Takao , Kobayashi Tsuyoshi , Shimomura Manabu , Yoshimitsu Masanori , Toyota Kazuhiro , Nakahara Masahiro , Ishizaki Yasuyo , Hirata Yuzo , Kodama Shinya , Shimizu Yosuke , Kawaguchi Koji , Tokunaga Masakazu , Sumitani Daisuke , Ohdan Hideki 
Published: February 2017

728 Background: mFOLFOX6 regimen, which is a standard regimen for metastatic colorectal cancer (CRC), is inconvenient owing to its requirement for continuous infusion via vascular access. We aimed to investigate the efficacy and safety of S-1/oxaliplatin (SOX) plus bevacizumab, a promising alternative treatment to replace mFOLFOX6. Methods: We undertook a clinical phase II trial in 12 institutions in Hiroshima, Japan. We enrolled individuals aged 20–80 years who had metastatic CRC, had an Eastern Cooperative Oncology Group performance status (PS) of 0 or 1, had assessable lesions, and had received no previous chemotherapy. Eligible patients were assigned SOX plus bevacizumab (S-1: 80-120 mg/body/day, day 1–14 orally administrated, oxaliplatin: 130mg/m2 day 1 i.v., bevacizumab: 7.5mg/kg day 1 i.v. q3w). The primary endpoint was response rate (RR), and the secondary end points were progression-free survival (PFS), overall survival (OS), and safety. Results: From May 2011 to January 2014, 55 patients (mean age, 64 years) were enrolled. The number of metastatic organs were one: 29 cases (52.7%), two or more: 25 cases (45.4%), and 2 cases had no target lesions (3.6%). Median follow up time was 12.8 months (range, 1.4-38.6 months). RR was 45.4% (95% CI, 32.2%-58.6%) and disease control rate was 87.3% (95% CI, 78.5-96.1%). Median PFS and OS time were 9.2 months (95% CI, 7.6-10.8) and 22.0 months (95% CI, 17.7-26.2), respectively. The median number of cycles of chemotherapy was 7 (range, 1-16). The median relative dose intensity of oxaliplatin, S-1, and bevacizumab were 85%, 85%, and 87%, respectively. Major toxic effects (grade 3/4) were thrombocytopenia (5.7%), neutropenia (7.5%), sensory neuropathy (13.2%), and anorexia (17.0%). Conclusions: These data indicated that the SOX plus bevacizumab regimen is effective and well tolerated in patients with metastatic CRC. Clinical trial information: UMIN000004976.
Angiopoietin-like protein 2 as a novel biomarker for diagnosis and prognosis in esophageal cancer.
Authors: Ide Shozo , Toiyama Yuji , Shimura Tadanobu , Mori Koichiro , Noguchi Tomofumi , Imaoka Hiroki , Okigami Masato , Yasuda Hiromi , Kitajima Takahito , Saigusa Susumu , Ohi Masaki , Tanaka Koji , Araki Toshimitsu , Inoue Yasuhiro , Mohri Yasuhiko , Kusunoki Masato 
Published: February 2017

73 Background: Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein with homology to the angiopoietins and overexpression of ANGPTL2 is known to act as a causative mediator of chronic inflammatory carcinogenesis. Recently, expression in tumor cells which are associated with tumor progression has been recognized in lung, breast, colon and gastric cancer. However, to our knowledge, functional and clinical significance of ANGPTL2 expression has not been investigated in esophageal cancer (EC). Aim: We investigated the functional roles of ANGPTL2 in vitro assay and evaluated the clinical significance of ANGPTL2 expression in both primary tumor and matched serum in patients with EC. Materials and Methods: First, in vitro assays were performed for functional analysis of ANGPTL2 using small interfering RNA (siRNA). Next, ANGPTL2 expression in EC tissues was evaluated by immunohistochemically (IHC) in 71 EC patients. Finally, we investigated serum ANGPLT2 levels from EC patients (n=71) and healthy controls (n=35) by ELISA. Results: Knockdown of ANGPTL2 expression decreased proliferative, invasive and migrated capacity in EC cell lines. ANGPTL2 expression in EC tissues was significantly elevated in EC patients with high T stage, squamous cell carcinoma, and high TNM stage. Kaplan–Meier analysis showed that patients with high expression of ANGPTL2 had significantly poorer overall (p<0.01) and disease-free survival (p<0.01) than those with low expression, respectively. Furthermore, multivariate analysis revealed that high ANGPTL2 expression in EC tissues was an independent predictive marker for poor prognosis (HR: 2.30, p=0.04). On the other hands, serum ANGPTL2 levels in EC patients was significantly elevated compared to healthy controls (p<0.001), and it can discriminate EC patients from healthy controls with high accuracy (AUC=0.913). However, no significant association between serum ANGPTL2 levels and clinicopathological findings were recognized in EC patients. Conclusions: We have demonstrated several novel evidences for biological and clinical significance of ANGPTL2 in EC. This study indicates ANGPTL2 had the potential to be useful as a biomarker in EC.
Factors associated with receipt of radiation therapy for rectal cancer.
Authors: Sussman Daniel A. , McClure Laura A. , Hernandez Monique N. , Tannenbaum Stacey L. , Bonner Judith M. , Zheng D. Diane , Lee David J. 
Published: February 2017

747 Background: Appropriate treatment for rectal cancer is vital to increasing the likelihood of survival. Disparities in receipt of appropriate radiation treatment have been observed with respect to race/ethnicity and socioeconomic status. We used enriched cancer registry data to identify alternative factors associated with receipt of appropriate radiation therapy for rectal cancer. Methods: Data were obtained from the Florida Cancer Data System and were enriched with detailed treatment information collected from a Centers for Disease Control and Prevention Comparative Effectiveness Research study. Using multivariable regression, we evaluated factors associated with receipt of radiation therapy among rectal cancer cases summary stage II/III. Our sample (n=403) included cases diagnosed in Florida in 2011 who were 18 years and older. Cases clinically staged as 0/1/4 were excluded. Though patients over age 80 years (n=67) and those with stage IIA disease (n=185) may not routinely be prescribed radiation, these cases were included in order to maximize the sample size. Results: Our sample was an average of 64 years-old, more often male (59%), NH White (56%), diagnosed with stage III disease (54%), insured (92%), had received surgical intervention (87%), chemotherapy (68%), or radiation (57%), were in the highest SES quartile (56%), and had one or more comorbid condition (57%). Older age (OR=0.96; 95%CI=0.94-0.97), the presence of more than one comorbidity (0.61; 0.39-0.96), and receipt of surgical intervention (0.44; 0.22-0.90) were predictors of not receiving radiation. Conclusions: Contrary to our hypothesis, socio-demographic factors such as race/ethnicity, insurance status, and socioeconomic status, did not influence the receipt of radiation. Further research is needed, however, to understand why age, comorbidity, and surgery present a barrier to radiation, particularly given that radiotherapy is a well-tolerated modality.
Association of early tumor shrinkage with progression-free survival in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy: HGCSG0802.
Authors: Nakatsumi Hiroshi , Yuki Satoshi , Muranaka Tetsuhito , Fukushima Hiraku , Kato Takashi , Meguro Takashi , Nakamura Michio , Iwanaga Ichiro , Ehira Nobuyuki , Sonoda Norikazu , Kudo Mineo , Kato Kanji , Miyashita Kencho , Abe Masakazu , Miyamoto Noriyuki , Sakamoto Keita , Kudo Kohsuke , Sakamoto Naoya , Sakata Yuh , Komatsu Yoshito 
Published: February 2017

749 Background: It was reported that early tumor shrinkage (ETS) was associated with better overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC) receiving cetuximab. We investigated association of ETS with progression free survival (PFS) in pts with unresectable colorectal liver metastases (CLM) from HGCSG0802 observational cohort study in pts with mCRC treated with first-line bevacizumab (BV)-based chemotherapy. Methods: The objective of HGCSG0802 was to evaluate PFS, OS, time to treatment failure (TTF), response rate (RR), safety and so on. The key eligibility criteria were evaluable lesions, older than 20 years old, ECOG PS 0-2. In this analysis, association of ETS at 8 weeks from the start of chemotherapy with pts characteristics, PFS and TTF was evaluated. Pts characteristics were compared using Student-t test, chi-square test and Fisher’s exact test. PFS and TTF were analyzed with Kaplan-Meier method and compared using log-rank test. Univariate analysis for the association of pts characteristics with PFS and TTF was performed using log-rank test, and multivariate analysis was performed using Cox proportional hazards model. Results: Of 108 pts (the full analysis set), 74 pts with CLM were evaluable for ETS. Forty-nine pts (66.2%) had ETS ≥20%. The pts characteristics between ETS ≥20% and <20% were well balanced. The median PFS was 7.3 months in ETS <20% versus 10.0 months in ETS ≥20% (HR 0.55; p=0.025). In multivariate analysis for PFS, there was no significant difference between ETS ≥20% and <20% (HR 0.585; p=0.066). The median TTF (ETS <20% v ≥20%) was 5,1 months vs. 7.7 months (HR 0.46; p=0.003). In multivariate analysis for TTF, there was significant difference between ETS ≥20% and <20% (HR 0.509; p=0.017). Conclusions: In this analysis, ETS ≥20% might be positive predictive marker for PFS and TTF in pts with CLM receiving first-line BV-based chemotherapy.
Intratumor heterogeneity of DNA copy number aberrations in gastric and oesophageal adenocarcinomas.
Authors: Davies Matthew N , Alpar Donat , Griffiths Beatrice , Barber Louise J , Lipinski Kamil A , Eltahir Zakaria , Agoston Emese , Harsanyi Laszlo , Wotherspoon Andrew , Szasz A Marcell , Gerlinger Marco 
Published: February 2017

78 Background: DNA copy number aberrations (CNAs) are common in oesophageal and gastric adenocarcinomas (OGCs) and display extensive inter-tumour heterogeneity. CNA patterns define gastric cancer molecular subtypes and ERBB2 amplifications, present in a small fraction of patients with OGC, are predictive for ERBB2-targeted drug sensitivity. Together, this suggests a critical role of CNAs determining OGC tumour biology and clinical outcomes. Despite this, predictive and prognostic CNA biomarkers have not been identified for the majority of OGCs, precluding the development of effective personalized therapy approaches for these aggressive tumours. Intra-tumour heterogeneity, characterized by the presence of multiple subclones with distinct genetic profiles within an individual cancer, can hinder the accurate molecular analysis and classification of tumours. The aim of this pilot study was to assess whether chemotherapy-naïve localized OGCs display intra-tumour macroheterogeneity of CNA profiles. Methods: Tissue specimens from four tumour regions representing the macroscopic spatial extent of each of five OGCs were systematically collected after surgical resection. DNA extracted from these FFPE specimens was analysed by molecular inversion probe SNP arrays for high resolution CNA detection. Results: Comparison of genome wide copy number and B-allele frequency profiles suggested highly concordant CNA profiles across the regions from individual primary tumours. Eight driver CNAs leading to amplification of the MET, KRAS, ERBB2, PIK3CA or FGFR2 oncogenes were identified in 4/5 tumours. Only one out of these eight driver CNA’s, harbouring the KRAS oncogene, was heterogeneous within a tumour. Conclusions: Although chromosomal instability is thought to be common in this tumour type, this pilot study suggests that macroheterogeneity is limited and that CNA profiles assessed from a single tumour biopsy are likely to be representative of the dominant CNA profile of localized OGCs. Thus, clinical correlative CNA analyses may be possible from single biopsies of localized OGCs. Mutational heterogeneity and microheterogeneity in microdissected and single cells are currently being investigated.
Observational cohort study of first-line bevacizumab combined with chemotherapy in metastatic colorectal cancer (HGCSG0802): Sub-group analysis by KRAS Exon2 status.
Authors: Takahata Takenori , Yuki Satoshi , Nakatsumi Hiroshi , Harada Kazuaki , Fukushima Hiraku , Sato Atsushi , Kato Takashi , Meguro Takashi , Nakamura Michio , Ehira Nobuyuki , Iwanaga Ichiro , Tateyama Miki , Hatanaka Kazuteru , Eto Kazunori , Okuda Hiroyuki , Kobayashi Yoshimitsu , Muto Osamu , Abe Masakazu , Sakata Yuh , Komatsu Yoshito 
Published: February 2017

782 Background: A few reports have shown the efficacy of bevacizumab (BV) independent of the KRAS Exon2 mutational status (KRAS). We performed a sub-group analysis by KRAS from the HGCSG0802 observational cohort study with investigated 115 patients (pts) treated with first line BV for metastatic colorectal cancer (mCRC). Methods: The objective of HGCSG0802 was to evaluate progression-free survival (PFS), overall survival (OS), time to treatment-failure (TTF), response rate (RR), safety, etc. The key eligibility criteria were with evaluable lesions, older than 20 years, ECOG PS 0-2. In this analysis, pts characteristics, RR and safety were compared using Fisher’s exact test. Univariate and multivariate analysis for PFS were performed using patient characteristics. Survival analyses were performed with Kaplan-Meier method, log-rank test, and Cox proportional hazards model. Results: Of 108 pts (the full analysis set), 98 pts were evaluable for KRAS. Sixty-one pts (62.2%) had KRAS wild-type (wt) and 37 pts (37.8%) had mutation (mt). The pts characteristics between those with wt and with mt were generally balanced except for PS 0 (91.8% in wt, 75.7% in mt; p=0.037) and lung metastasis (34.4% in wt, 62.2% in mt; p=0.012).The median TTF was 7.4 months in wt versus 6.6 months in mt, and RR was 69.5% in wt versus 65.7% in mt. Adverse events related to BV were almost balanced except for bleeding (any grade) (31.1% in wt, 13.5% in mt; p=0.056).The median PFS was 9.9 months in wt versus 7.9 months in mt (HR=1.506; p=0.071). Although KRAS mt showed shorter PFS, there were not significant difference regardless of KRAS in Cox multivariate analysis (HR 1.314, 95% CI, 0.820-2.107, p=0.257). Conclusions: The HGCSG0802 could be a database to investigate first line BV for mCRC in clinical practice. Depending on the KRAS Exon2 mutational status, efficacy, and adverse events were no significant difference. We plan to conduct further follow up for survival, and to perform this analysis again.