bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor sidedness, adjuvant chemotherapy (AC), and other factors affecting survival in patients with stage II colon cancer (CC-II).
Authors: Mukkamalla Shiva Kumar Reddy , Huynh Donny V. , Somasundar Ponnandai Sadasivan , Rathore Ritesh 
Published: March 2017

768 Background: The role of AC in CC-II is not well defined due to lack of conclusive randomized trial data. This updated analysis using National Cancer Database (NCDB) addresses the overall survival (OS) benefit from AC in CC-II using more refined and case appropriate population cohort. Methods: NCDB was queried for patients diagnosed with CC-II from 2004-2008 with survival information through 2013. Only those patients with pathologically confirmed CC diagnosis were included. Patients undergoing any surgical procedure less than a partial colectomy were excluded. Pearson Chi-square test, Kaplan Meier survival curves and Cox proportional hazards model were used for statistical analysis. Results: A cohort of 36,630 patients was identified for analysis. Elderly patients received less frequent AC (p < 0.0001) and AC was associated with an improved 5-year OS with no difference noted in outcomes from single or multi-agent regimens. AC was an independent predictor of OS regardless of age, gender, race, comorbidity index, insurance status, income level, year of diagnosis, tumor sidedness, tumor grade, adequacy of lymph node evaluation, pathologic tumor (pT) status, colectomy type, margin involvement or academic level of treating institution. In multivariate analysis, right-sided cancers had better survival outcomes compared to left-sided cancers (HR 0.91; p < 0.0001). Conclusions: This study validates previous findings of improved OS from AC in CC-II while addressing some of the shortcomings of prior retrospective studies. Only patients with CC-II without any other primary cancer diagnoses were included. To our knowledge this is the most uptodate analysis of AC in CC-II which includes cases diagnosed up to 2008. Our study found similar improvement in 5-year OS irrespective of chemotherapy regimen. Interestingly, improved OS was seen in right sided tumors compared to left sided tumors, in contrary to that seen with metastatic colon cancer (Venook et al). [Table: see text]
Clinical efficacy and safety of regorafenib (REG) in the treatment of metastatic colorectal cancer (mCRC) in daily practice in Germany: Interim results of the prospective multicentre noninterventional RECORA study.
Authors: Schulz Holger , Janssen Jan , Strauss Uwe P. , Langen Markus , Frey Marcel , Fiala-Buskies Sabine , Bokemeyer Carsten 
Published: March 2017

769 Background: In 2013 REG was approved for mCRC based on the results achieved in the CORRECT trial. However, prospective data from daily practice use are still scarce. Methods: RECORA is investigating efficacy and safety of REG in routine clinical care in Germany. Male/female mCRC patients (pts) ≥ 18 years for whom the decision was taken to treat with REG in its approved indication were enrolled. Primary objective was overall survival (OS). Secondary objectives included progression-free survival time (PFS), time-to-progression (TTP), disease control rate (DCR), and incidence of treatment-emergent adverse events (TEAE). Results of a planned interim analysis with data cut-off 11 July 2016 are presented. Results: 480 pts were enrolled at 90 sites between 10/13 and 07/16; 458 pts were included in this interim analysis for safety, 457 for efficacy. Mean/median age was 67 years, 61% of pts were male, baseline ECOG PS was 0 in 20%, 1 in 61%, 2 in 18%, and 3 in 1% of pts, 62% had a primary colon cancer, 46% had KRAS mutated tumors at diagnosis, 23% had mets in the liver only, 9% in the lung only, and 22% in both lung and liver. Median OS was 5.6 months (mos) (95% CI 5.2-6.6) based on 277 deaths, median PFS was 3.2 mos (95% CI 2.9-3.5) based on 337 progression or death events, median TTP was 4.5 mos (95% CI 3.8-5.4) based on 195 progressions, DCR was 29.9% based on 234 tumor evaluations. There were no significant differences in OS in subgroups according to age ( < 65/ ≥ 65), sex, KRAS status, number of prior treatment lines, and site of mets; whereas OS was significantly different in subgroups according to ECOG PS (ECOG 0/1 vs. 2), primary tumor site, and time from initial diagnosis ( < 18/ ≥ 18 mos). Mean duration of treatment was 2.7 mos. TEAE grade ≥ 3 occurred in 23.7% of pts, in 17.3% REG related. A serious TEAE was recorded in 47.8% of pts, in 8.3% considered as REG related. Overall, 26.6% died of an AE, in 0.4% REG related. 23.8% of pts received another anti-tumor therapy after REG was stopped. Conclusions: RECORA showed clinical benefit and acceptable tolerability for REG in this interim analysis. OS was in the range of the pivotal study. Clinical trial information: NCT01959269.
Intermittent maintenance treatment with bevacizumab in patients with metastatic colorectal cancer: A single centre experience.
Authors: Cerchiaro Eleonora , Squadroni Michela , Sauta Maria Grazia , Bonomi Maria , Brena Federica , Ripa Cristina , Barile Rosalba , Salvini Piermario , Ceresoli Giovanni Luca , Beretta Giordano D. 
Published: March 2017

776 Background: The main objective of care in patients with metastatic colorectal cancer (mCRC) is survival prolongation preserving the quality of life (QoL). Optimal duration of chemotherapy after induction treatment is still a matter of debate, such as the treatment strategies that could be adopted (intermittent versus continuous maintenance chemotherapy). Methods: In this monoinstitutional retrospective study we evaluated 70 patients (pts) diagnosed with mCRC with stable or responsive disease after chemotherapy with Bevacizumab (12 courses of FOLFIRI-Bevacizumab) as first or second-line treatment. We observed three groups: group A (20pts): maintenance therapy with de Gramont-Bevacizumab 2 months on/2 months off until disease progression (intermittent strategy); group B (30 pts): no maintenance treatment; group C (20 pts): induction treatment exclusively as first line followed by continuous maintenance with de Gramont-Bevacizumab. Results: Median progression free survival (PFS) was 21 months in Group A (range: 10-51 months), 9 months in Group B (range 6.6-12.9 months), 11 months in groups C (range 10.4-13.3 months), the difference resulted significant among group in favor of intermittent strategy (p = 0.006). Median OS was 60.6 months (range: 35.6-96.2 months) in group A, 27.2 months (range 19.5-39.9 months) in group B and 23.6 months in group C (range: 19.1-31 months); p = 0.0011. The most frequent adverse events of all grades were: hypertension, neutropenia, thrombocytopenia, diarrhea, asthenia. No toxic death was observed. Adverse events (AEs) of all grades were more frequent in group C (15% Grade 3-4), comparing with Group A and B (10% Grade 3-4 AEs) Conclusions: According to our retrospective analysis, intermittent maintenance treatment with chemotherapy and Bevacizumab appears to be a feasible strategy in pts with stable or responsive disease. PFS and OS resulted longer in patients treated with intermittent strategy comparing with other groups. The study has at least three bias: selection of patients, small sample size and retrospective nature, however we can conclude that intermittent strategy could improve patients outcome with an acceptable toxicity profile.
Bevacizumab in addition to chemotherapy first-line for right-side metastatic colorectal cancer: A cost-effectiveness analysis.
Authors: Chen Gong , Liu Maobai , Li Te , Wu Bin 
Published: March 2017

777 Background: To test the cost-effectiveness of bevacizumab treatment compared with cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for patients with right-side metastatic colorectal cancer (mCRC). Methods: A Markov model was developed to Chinese clinical practice. The model incorporated clinical and utility data from published literatures, resource utilization and unit prices based on local charge. The lifetime horizontal was used and sensitivity analyses were carried out to test the robustness of the model results. The impact of patient assistance program (PAP) was also evaluated in scenario analyses. Results: Baseline analysis showed that the addition of cetuximab gained additional 0.232 QALYs with more $60,371 relative to bevacizumab therapy, resulting in an ICER of $259,775 /QALY. When PAP was available, the incremental cost decreased to $24,161, which yielded an ICER of $60,371 /QALY, which indicated that the strategy was not cost-effective at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China ($22,200/QALY). Sensitivity analyses found that the costs of bevacizumab was the most influential parameter. Conclusions: Bevacizumab treatment for right-side mCRC is not a cost-effective option in comparison with standard chemotherapy in Chinese context.
Updated analysis: A retrospective cohort study evaluating the safety and efficacy of regorafenib in patients with metastatic colorectal cancer—HGCSG1401.
Authors: Ota Yumiko , Yuki Satoshi , Harada Kazuaki , Yoshida Shuntaro , Tsuji Yasushi , Kobayashi Yoshimitsu , Hatanaka Kazuteru , Okuda Hiroyuki , Sasaki Takahide , Dazai Masayoshi , Konno Jun , Ohta Tomoyuki , Honda Takuya , Ishiguro Atsushi , Muto Osamu , Sato Yasushi , Kato Sosuke , Onodera Kei , Sakata Yuh , Komatsu Yoshito 
Published: March 2017

778 Background: The CORRECT trial revealed the safety and efficacy of regorafenib (REG) for patients (pts) with colorectal cancer including Japanese. REG was approved in Japan in March 2013. However, there are few studies exploring the efficacy and safety of REG in a large number of patients, particularly in daily practice. Methods: We analyzed 173 pts who received REG from May 2013 in the multi-institutional retrospective study (HGCSG1401). This study was analyzed by CTCAE v4.0 for adverse events (AEs), RECIST v1.1 for response rate (RR)/disease control rate (DCR), and Kaplan-Meier method for progression free survival (PFS) and overall survival (OS). Results: Patients’ characteristics were as follows; male/female 98/75, median age 66 (range 29-87), ECOG PS (0/1/2/3) 58/96/18/1, KRAS Exon2 wild/mutant 98/74 (1 patient ; KRAS Exon2 status was not tested). The initial starting dose was 160 mg (n = 145, 83.8%), 120mg (n = 22, 12.7%), and 80mg (n = 6, 3.5%) respectively. Dose reductions were required in 73 pts (42.2%); 38 pts (22.0%) discontinued therapy due to AEs. The common ≥ grade 3 AEs ( ≥ 15%) were palmar-plantar erythrodysesthesia syndrome (n = 48; 27.7%), hypertension (n = 34; 19.7%), proteinuria (n = 24; 19.2%) and AST increased (n = 24; 13.9%). RR and disease control rate (DCR) were 1.3% and 29.6%, respectively. Median PFS and median survival time (MST) were 2.1 and 6.3 months. In an analysis on relationship between ECOG PS (PS 0-1 vs. PS 2-3) and efficacy, median PFS was 2.3 vs. 1.2 months (HR 3.598, p < 0.001), and MST was 7.0 vs. 2.1 months (HR 4.751, p < 0.001). Conclusions: The efficacy of REG in pts with PS 0–1 was similar to the previous report; however, REG was not effective in patients with PS 2–3. In adverse events, hypertension and liver dysfunction were expressed more frequently than previously reported. We will continue the analysis of the factors associated with liver dysfunction and prognostic/predictive factors.
The risk factors for vomiting and nausea in patients with oxaliplatin-based chemotherapy: Subgroup analysis of SENRI trial.
Authors: Nishimura Junichi , Kudo Toshihiro , Takemoto Hiroyoshi , Komori Takamichi , Kim Ho Min , Ota Hirofumi , Suzuki Rei , Ikenaga Masakazu , Ikeda Masataka , Yamamoto Hirofumi , Satoh Taroh , Hata Taishi , Takemasa Ichiro , Mizushima Tsunekazu , Doki Yuichiro , Mori Masaki 
Published: March 2017

779 Background: We previously reported, in the SENRI trial, usefulness of aprepitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in colorectal cancer patients receiving an oxaliplatin-based regimen which is classified as moderately emetogenic cancer chemotherapy. In this study, we assessed the risk factors for CINV in colorectal cancer patients who received Oxaliplatin-based chemotherapy. Methods: A total of 370 patients was analyzed as for the rate of vomiting, and significant nausea in overall phase. We also assessed the proportion of CINV in patients divided by gender. Results: First, we analyzed the risk factors for vomiting and nausea. Female gender and aprepitant use were associated with the incidence of vomiting and significant nausea. Significantly more women suffered from vomiting than men (84.5 % vs. 92.9 % in women and men, respectively; P= 0.0001). The rate of no nausea, complete response, complete protection, and total control was also lower in women. The rate of use of rescue therapy was significantly higher in women. We compared the rate of CINV between aprepitant and control groups and found that, in women, the rate of no nausea, no vomiting, and total control was higher in the aprepitant group than in the control group. Conclusions: Gender and no aprepitant use were risk factors of CINV in colorectal patients who received oxaliplatin-based chemotherapy.Aprepitant therapy was more effective for women than for men in the prevention of CINV in colorectal cancer patients receiving an oxaliplatin-based regimen. Clinical trial information: NCT01344304.
Methionine gamma-lyase-encapsulated into red blood cells (ERY-MET) antitumor activity in gastric carcinoma.
Authors: Bourgeaux Vanessa , Sénéchal Karine , Aguera Karine , Gay Fabien , Horand Françoise 
Published: March 2017

78 Background: Methionine (Met) requirement is a cancer specific–metabolic defect that seems a promising target, especially in gastric cancers. Methionine gamma–lyase (MGL), a pyridoxal–5′–phosphate (PLP)–dependent enzyme, is an emerging approach consisting in tumors Met starvation via systemic Met depletion. ERY-MET is a new therapeutic product overcoming the short in vivo half-life of free MGL by its encapsulation into Red Blood Cells (RBCs). Indeed, ERY-MET works as a bioreactor degrading Met that passively diffuses inside the RBC. In addition, entrapped MGL activity can be controlled by supplying Vitamin B6 (PN), the precursor of MGL’s cofactor (PLP), converted inside RBCs. ERY-MET anti-tumor activity was evaluated in vivo in NMRI nudemice bearing subcutaneous gastric carcinoma. Methods: First, in vitro sensitivity of NCI-N87 and AGS human gastric cell lines to free MGL was assessed by IC50 determination using CCK–8 assay. MGL encapsulated into mouse RBCs by hypotonic dialysis was injected once in CD1 mice to determine PK-PD parameters with or without PN supplementation. The anti-tumor activity of weekly ERY-MET injections (x5) at 116 IU/kg ± 25% was assessed with or without PN supplementation in female NMRI nudemice (n = 10/group) xenografted with NCI-N87 cells. Met depletion was determined 6 days after each cumulative injection while tumor growth was followed twice a week by caliper measurement. Results: In vitro studies showed that NCI-N87 as well as AGS cell lines displayed a sensitivity to free MGL with IC50 of 0.35 ± 0.01 and 0.12 ± 0.02 IU/mL, respectively. ERY-MET with daily PN supplementation significantly increased active MGL half-life in vivo (from < 24h to 8–9 days). ERY-MET induced 80% inhibition of tumor growth at day 45 (p < 0.0001). Response rate obtained was 76% of treated mice (15/20). Besides, PN supplementation induced a slow-down of tumor growth during the supplementation period and improved ERY-MET efficacy. Conclusions: Theses results suggest that ERY-MET can induce tumor growth inhibition in mice bearing human gastric adenocarcinoma and that its effect can be regulated by PN supplementation. As such, ERY-MET seems a promising anti-tumor drug to treat gastric cancers.
ECOG performance status as a predictor of adjuvant chemotherapy (AC) toxicities in stage III colorectal cancer (CRC) patients.
Authors: Watanabe Akie , Yang Charlie , Cheung Winson Y. 
Published: March 2017

789 Background: Toxicities acquired from AC can greatly impact quality of life. ECOG performance status is a clinical factor that is frequently considered in AC treatment decision-making, but its associations with common toxicity outcomes remain unclear. Methods: We reviewed a cohort of 371 CRC patients treated with adjuvant monotherapy (Capecitabine) or combination therapy (FOLFOX or CAPOX) within 12 weeks of curative resection at the British Columbia Cancer Agency, and determined the associations between ECOG (0, 1, ≥ 2) and toxicity outcomes. We also categorized toxicities into early, intermediate, or late based on their time of onset. Results: Among 371 patients, median age was 65 years, 52% were men, and 45%, 41%, and 14% were ECOG 0, 1, and ≥ 2, respectively. In this cohort, 41% received monotherapy and 59% received combination therapy. There was a trend of decreased toxicity for specific side effects, such as nausea, vomiting, and diarrhea, with each additional treatment cycle. For monotherapy, ECOG was found on univariate analyses to be associated with several toxicities including early onset hand foot syndrome and early onset anemia (both P < 0.05). When compared to ECOG 0, multivariate analyses showed that patients with worse ECOG were more likely to develop early hematological toxicities (ECOG 1, OR 2.75, 95% CI 1.01-7.49, P= 0.04; ECOG ≥ 2, OR 4.38, 95% CI 1.24-15.49, P= 0.02). ECOG ≥ 2 patients also had higher odds of experiencing late hematological toxicities (OR 4.52, 95% CI 1.05-19.52, P= 0.04) and neuropathy (OR 5.73, 95% CI 1.25-26.14, P= 0.02). In univariate analyses of combination therapy, ECOG was associated with early gastrointestinal and late hematologic toxicities (both P < 0.05). On multivariate analyses, however, ECOG was predictive of only early hematologic toxicities (ECOG 1, OR 2.13, 95% CI 1.05-4.32, P= 0.04; ECOG ≥ 2, OR 3.85, 95% CI 1.18-12.6, P= 0.03). Further analyses did not show any consistent correlations between ECOG and other toxicity outcomes. Conclusions: Although specific toxicities appear to decrease with each successive cycle of AC, poor ECOG is associated with an increased likelihood of certain side effects that can further inform AC discussions.
The efficacy and safety of CapeOX plus bevacizumab therapy with a planned oxaliplatin stop-and-go strategy in patients with metastatic colorectal cancer: A multi-center, single-arm, phase II study (CCOG-0902 study).
Authors: Sunakawa Yuuki , Nakayama Goro , Ishigure Kiyoshi , Yokoyama Hiroyuki , Uehara Keisuke , Kanda Mitsuro , Murotani Kenta , Fujii Tsutomu , Kodera Yasuhiro 
Published: March 2017

795 Background: The aim of this study was to evaluate the efficacy and safety of CapeOX plus bevacizumab with a planned oxaliplatin stop-and-go strategy in Japanese patients with metastatic colorectal cancer (mCRC). Methods: Patients with untreated mCRC were treated with 4 cycles of CapeOX plus bevacizumab therapy, followed by capecitabine plus bevacizumab maintenance therapy. Reintroduction of oxaliplatin was scheduled after 8 cycles of maintenance therapy or upon tumor progression. The primary endpoint was progression-free survival (PFS), and secondary end points included overall survival (OS), objective response rate to each treatment, reintroduction rate of oxaliplatin, frequency of peripheral sensory neuropathy (PSN), and safety. Results: The 52 patients who received the protocol treatment were included in the evaluation of efficacy and safety. Median PFS and OS were 12.4 months (95% confidence interval [CI], 10.0–14.8) and 30.6 months (95% CI, 27.6–33.5), respectively. The objective response rates were 55.8% for the initial CapeOX plus bevacizumab therapy, 17.8% for capecitabine plus bevacizumab maintenance therapy, and 31.0% for reintroduced CapeOX plus bevacizumab therapy. The frequency of PSN was 63.5%, including 3.8% of patients with grade 3 PSN. No patients required treatment discontinuation because of PSN during the induction or maintenance therapy. Conclusions: CapeOX plus bevacizumab therapy with a planned oxaliplatin stop-and-go strategy is a feasible first-line treatment for Japanese patients with mCRC. Clinical trial information: UMIN000006478.
Evaluation and response of mucin pools in primary rectal cancer tissue during chemoradiotherapy (CRT).
Authors: Miyakita Hiroshi , Sadahiro Sotaro , Saito Gota , Okada Kazutake , Tanaka Akira , Suzuki Toshiyuki 
Published: March 2017

798 Background: Mucinous carcinoma (MC) has been defined as carcinoma with > 50% of tumor volume showing mucin pool (MP). The incidence of MC had been reported to be 4 to 12% of colorectal cancer and to be less effective for chemotherapy and CRT. The incidence of MC was 3 to 8% in rectal cancer treated with surgery alone and 13 to 24% in patients treated with CRT. These findings suggest that MP may be induced by CRT in some patients. We therefore compared the degree of MP in MRI findings before CRT, after CRT and in resected specimens. Methods: The study group comprised 205 patients with rectal cancer who received CRT (40 to 45 Gy) from 2006 through 2014. MPs on MRI were evaluated using T2-weighted fast-spin echo images, and the MP area ratios on maximum cross-section of the primary tumor were calculated. An MP area ratio of 0% was designated as class 0, 1 to 9% as class I, 10 to 29% as class II, 30 to 50% as class III, and 50% or higher as class IV. Results: On MRI before CRT, the MP area ratio was class 0 in 181 patients (88%), class I in 11 (5%), and class II or higher in 13 (6%). On MRI after CRT, the MP area ratio was class 0 in 186 patients (91%), class I in 4 (2%), and class II or higher in 15 (7%). The prevalence of MP classes did not change appreciably. The MP class evaluated on MRI before and after CRT changed by 2 or more levels in only 2 patients, both of whom had marked tumor shrinkage. Among 175 patients with an MP area ratio of class 0 or I in the resected specimens, the MRI findings after CRT were consistent with the findings of the resected specimens. However, the MP area ratio was underestimated by 2 or more levels on MRI in 14 (47%) of 30 patients who had an MP area ratio of class II or higher. A pathological complete response (pCR) was obtained in 24 patients (12%), all of whom had an MP area ratio of class 0 or I on MRI before CRT. No patient with an MP area ratio of class II or higher before CRT had a pCR. Conclusions: The degree of MP evaluated on MRI did not change during CRT. In patients who had an MP area ratio of > 10% in their resected specimens, the evaluation of MP on MRI was often underestimated. Patients with an MP area ratio of > 10% before CRT had a poor response to CRT, with no pCR.