bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rates of pathologic complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with or without regional pelvic hyperthermia for locally advanced rectal cancer.
Authors: Gani Cihan , Schroeder Christopher , Lamprecht Ulf , Bamberg Michael , Berger Bernhard 
Published: February 2017

622 Background: Regional pelvic hyperthermia is frequently added to neoadjuvant radiochemotherapy for locally advanced rectal cancer. The present retrospective study is the first to evaluate the impact of hyperthermia on rates of complete pathologic response and sphincter-sparing surgery in the context of a standard up-to-date neoadjuvant radiochemotherapy scheme. Methods: Between 2007 and 2010, 85 consecutive patients with locally advanced cancer (cT3, cT4, cN+) of the middle and lower rectum received neoadjuvant radiochemotherapy at our institution. 45 of 85 patients (“RCT group”) received standard treatment consisting of radiotherapy to the pelvis with 5040 cGy in 28 fractions of 180 cGy and 5-fluorouracil as a continuous infusion with 1000 mg/m² over 120 hours during the first and fifth week of treatment. 40 of 85 patients (“HRCT group”) received the same treatment with at least four treatments of weekly regional hyperthermia. Target temperature was 40.5°C for at least 60 minutes. Total mesorectal excision was routinely performed. Results: No significant difference in the distribution of age, gender, clinical stage and tumor grade was observed between both groups. Complete pathologic response was seen in 6.7% of patients in the RCT group and 22% of patients in the HRCT group (p=0.034). Overall rates of sphincter-sparing surgery were 64% in the RCT group and 65% in HRCT. However for deep seated tumors located within 4 cm of the anal verge (based on initial staging), sphincter sparing surgery was achieved in only 11.1% of patients in the RCT group but 35.7% of patients in the HRCT group (p = 0.19). Conclusions: The addition of regional hyperthermia to neoadjuvant radiochemotherapy significantly increases the rate of complete pathologic response, with a tendency towards higher rates of sphincter-sparing surgery for deep seated tumors.
Validation study of a prognostic classification system in patients with metastatic colorectal cancer who received irinotecan-based second-line chemotherapy.
Authors: Yamazaki Kentaro , Naito Yoichi , Yuki Satoshi , Kawamoto Yasuyuki , Yasui Hirofumi , Takano Toshimi , Komatsu Yoshito , Muro Kei , Shitara Kohei 
Published: February 2017

624 Background:Previously, five prognostic factors (ECOG PS 2, pathologically poorly differentiated adenocarcinoma, peritoneal metastasis, PFS of 1st-line therapy <6 months, and LDH >400 IU/L) were identified in 124 patients with metastatic colorectal cancer who received irinotecan-based second-line chemotherapy (Shitara K, et al. ASCO-GI 2009). Patients were categorized into three prognostic groups (low-risk = no factors, intermediate-risk = 1 factor, high-risk = 2 or more factors), with significant differences in median overall survival (23.5, 14.6, and 5.5 months, respectively). The purpose of this study was to validate this prognostic classification in an external validation cohort. Methods: We retrospectively analyzed 198 patients with metastatic colorectal cancer who received irinotecan-based second-line chemotherapy after first-line oxaliplatin-based chemotherapy in 3 institutions. This was our validation cohort. Results: The median overall survival of this validation cohort was not significantly different from that of the generating cohort (12.1 vs. 14.6 months; P=0.47). The distribution of the three prognostic groups in the validation cohort was as follows: low-risk (n=68; 35%), intermediate-risk (n=80; 41%), high-risk (n=45; 23%), with a higher proportion of intermediate-risk patients in comparison with the generating cohort. The median overall survival of each prognostic group in the validation cohort was 19.8, 11.0, and 7.9 months, respectively, with significant differences among groups (P<0.01), as was shown for the generating cohort. A similar tendency was observed for progression-free survival. Conclusions: Our results validated the previously defined prognostic classifications in patients with metastatic colorectal cancer who received irinotecan-based second-line chemotherapy. This classification may be useful as a stratification factor in clinical trials or in considering treatment strategies for individual patients.
Fast-track surgery in colorectal surgery: When laparoscopy is not an option.
Authors: Silva José Pedro Carvalho Moreira da 
Published: February 2017

642 Background: “Fast-track” protocols are multimodal programs that when applied to colorectal surgery, permit a reduction in morbidity, hospital stay and a faster recovery after the surgery. Most of these protocols are associated to laparoscopic surgery. However it is possible to reproduce these results with open surgery, when laparoscopy is not an option (lack of material or medical experience or in low-resource scenario). Methods: Main objective: 1) Apply a fast-track protocol, designed to our patients that have colon malignancies and are submitted to colon resections through an open procedure 2) To study the peri-operative morbidity in the first 30 days after surgery. We conducted a pilot study with 30 patients in 2007. After assuring the feasibility of this protocol we started to apply it regularly in 2009; 177 patients underwent to fast track open colorectal surgery until July 2011. Main studied outcomes were duration of the surgical procedure, pain control, postoperative complications, and length of hospital stay. Other variables included patient (demographic characteristics, BMI, ASA and POSSUM scores), tumour (TNM status) and surgery (type) related variables. Results: 54,8% of the patients were male. Median age was 63 years old (Min.: 36; Máx.: 79). 53,7% had sigmoid or rectosigmoid tumors. Most were classified as pT3N0 tumors. In 89% of the patients, epidural catheter was placed. 92,7% had a vertical median abdominal incision with a median of 19 cm (Min.: 10; Máx.: 30). The most performed surgery was the sigmoid colectomy and the anterior rectosigmoid resection. 89,3% tolerated oral clear liquids, 2 hours after surgery. 31,6% of the patients referred nauseas or vomits in the post-operative period. 83,6% didn't refer pain after the surgery. 2,83% had an anastomotic fistula and had to be reoperated (similarly to historical data). 36,7% were discharged at day three after surgery and 87% have been discharged by the 5th day. Conclusions: The “Fast-track” protocol applied to open colon surgery is feasible, doesn’t increase the morbidity or mortality and permits shorter hospital stays and is not expensive. To its success contribute the detailed information to the patient, the formation and the motivation of the health care people involved.
The management of patients with T1 adenocarcinoma of the low rectum: An updated decision analysis.
Authors: Johnston Calvin F. , Tomlinson George A. , Temple Larissa K. F. , Baxter Nancy N. 
Published: February 2017

645 Background: Patients with T1 adenocarcinoma of the low rectum are faced with a choice between Transanal Local Excision (TLE) and Abdonimoperineal Resection (APR). Fundamentally a tradeoff between quantity and quality of life, this problem is well-suited to decision analysis. A previous decision analysis examined this issue in 1999, but subsequent case series have reported TLE recurrence rates higher than that study considered plausible. Decision analytic techniques have also evolved by incorporating Markov modeling, which better accounts for the temporal aspects of the problem, and microsimulation, which allows for greater flexibility. Methods: We developed a Markov-type microsimulation to evaluate the decision between APR and TLE in T1 adenocarcinoma of the low rectum. We used the software package 'R' and have made all computer code freely available for full transparency. Critical parameters such as transition rates and utilities were elicited by systematic literature reviews and expert opinion. Conflicting values were resolved by weighted averaging and sensitivity analyses. Results: On average, selecting TLE over APR for T1 rectal cancer resulted in a loss of 0.53 years of life expectancy but a gain of 0.97 quality-adjusted life years; hence, TLE was considered the preferable option in the majority of patients. APR was preferred if and only if the patient was unwilling to yield 7% of his or her life expectancy to avoid a permanent stoma. This transition point shifted depending on the anticipated risk of recurrence after TLE. Sensitivity analysis indicated robustness of our findings. Conclusions: Though performing an APR for T1 adenocarcinoma of the low rectum does provide an extra six months of life expectancy, a TLE is the preferable approach for the majority of patients when quality-of-life is taken into consideration. The decision in an individual patient's case can be facilitated by tumour risk-stratification and by ascertaining the patient's willingness to yield life expectancy to avoid a permanent stoma.
First-line treatment of advanced colorectal cancer with bevacizumab in France: The ThInDiT observational cohort study.
Authors: Doat Solene , Samson Solene , Ricordeau Philippe , Guillemot Didier , Mitry Emmanuel 
Published: February 2017

655 Background: ThInDiT (Therapeutic Innovations in Digestive Tumors) is an ambispective observational cohort study based on the database of the French national health insurance system. Using this database, we analysed the use of bevacizumab in the front-line treatment of metastatic colorectal cancer. Methods: Patients and treatment characteristics were collected for 4 273 incident cases of colorectal cancer with synchronous metastases diagnosed between April 1st and September 30th 2009. A logistic regression was used to identify factors predictive of non-prescription of bevacizumab among patients receiving chemotherapy within the first three months. Results: 2 757 (64.5%) received chemotherapy, in combination with bevacizumab in 827 patients (30% of the treated patients). Median age was 64 years in the bevacizumab group against 70 years in the no bevacizumab group (p<0.0001). Major factors significantly associated with the non-prescription of bevacizumab in multivariate analysis were: age ≥ 75 years (OR= 2.47, IC95% 1.9-3.1), unresected primary tumour (OR=1.44, IC95% 1.2-1.8), rectal site (OR= 1.37, IC95% 1.1-1.8), peritoneal carcinosis (OR=1.37, IC95% 1.1-1.7), radiotherapy within the last month (OR=3.59, IC95% 2.1-6.1), arterial (OR= 1.72, IC95% 1.1-2.6) or venous (OR=2.04, IC95% 1.3-3.1) thromboembolic event within 6 months, arterial hypertension (OR=1.37, IC95% 1.1-1.7), wound (OR=3.35, IC95% 1.3-8.7), chronic bronchopneumopathy (OR=1.66, IC95%: 1.0-2.7), nephropathy (OR=2.69, IC95% 1.5-4.7). Brain metastasis and colonic endoprothesis were not associated. 1-year overall survival rate was 81% in the bevacizumab group and 76% in the no bevacizumab group. Conclusions: Based on the database of the national health insurance system, this analysis reports data on the use of chemotherapy in combination with bevacizumab in the French population, reflecting the real life practice among non-selected patients. About 2/3 of the patients with synchronous metastatic colorectal cancer are treated with chemotherapy, in combination with bevacizumab in 30% of the cases. Patients receiving bevacizumab are younger with less comorbidities.
Treatment patterns and outcomes of acneiform eruptions from anti-epidermal growth factor receptor (EGFR) therapies for metastatic colorectal cancer (MCRC).
Authors: Dascalu Bogdan , Kennecke Hagen F. , Lim Howard John , Cheung Winson Y. 
Published: February 2017

668 Background: Use of anti-EGFR therapies, such as cetuximab (cmab) and panitumumab (pmab), is associated with acneiform eruptions. Because prior research suggests a possible correlation between rash severity and outcomes in unselected patients, concerns remain that prophylactic treatment of rash may interfere with anti-tumor activities of these drugs. Our aims were to: 1) characterize the treatment patterns for rashes due to cmab and pmab; and 2) evaluate if a prophylactic vs. reactive approach to rash management modifies outcomes. Methods: All patients diagnosed with wild-type K-ras MCRC from July 2009 to June 2011 in British Columbia, Canada and prescribed either cmab or pmab were identified. We conducted a detailed retrospective review to describe prophylactic (before rash) and reactive (after rash) use of antibiotics and steroid creams. Using Cox regression, the relationship between rash management and overall survival was characterized. Results: In total, 78 eligible patients were analyzed: median age was 62 years, 65% were male, 27% received cmab and 73% pmab, and median number of anti-EGFR treatment was 9 cycles. Rash occurred in 88% of patients. Among them, reactive treatment was favored over prophylactic treatment (74% vs. 26%). There were no differences in rash management based on any patient or tumor characteristics (all p>0.05). Median overall survival was 7.2 months. The number of treatment cycles and overall survival were similar in both prophylactic and reactive groups. In Cox regression, ECOG 2+ correlated with worse overall survival (HR for death 5.95, 95% CI 1.68- 21.13). However, outcomes were statistically similar between patients prescribed antibiotics prophylactically vs. reactively (HR=1.47, 95% CI 0.37-5.90) and between patients given steroid creams prophylactically vs. reactively (HR=0.75, 95% CI 0.11-4.88). Conclusions: Prophylactic treatment of anti-EGFR related rash is associated with similar outcomes as reactive rash treatment in wild-type K-ras MCRC patients. Because rash can lead to decreased quality of life, pre-emptive skin treatment represents a reasonable strategy for patients on anti-EGFR therapies.
Phase II trial of bevacizumab, irinotecan, cisplatin, and radiation as preoperative therapy in esophageal adenocarcinoma.
Authors: Ilson David , Goodman Karyn A. , Janjigian Yelena Yuriy , Shah Manish A. , Kelsen David Paul , Rizk Nabil P. , Rusch Valerie W. , Wu Abraham Jing-Ching , Campbell Jenny , Capanu Marinela , Bains Manjit S. 
Published: February 2017

67 Background: Preop chemo and radiotherapy (RT) with weekly irinotecan (I), cisplatin (C) and 5040 cGy is tolerable and active [Cancer, in press]. Bevacizumab (B) + weekly I/C in advanced esophagogastric cancer increased response rate and PFS without an increase in toxicity [JCO 24: 5201; 2006]. In a phase II trial in esophageal adenocarcinoma (EA) we combined B + I/C + RT as preop therapy. A toxicity analysis after 10 patients (pts) undergoing surgery indicated no unexpected toxicity with B [JCO 27: Abstract 4573; 2009]. We completed a planned accrual of 33 pts. Methods: Pts had resectable Siewert’s I or II EA, T2-3 or N1 staged by EUS, PET, and CT scan. Induction chemo: I 50-65 mg/m2 + C 30 mg/m2 weeks 1,2,4,5, B 7.5 mg/kg weeks 1 and 4; Chemort: 180 cGy daily fractions to 5040 cGy, I/C weeks 7,8,10,11+ B weeks 7,10. Esophagectomy was planned 6-8 weeks after RT. Postop: B 7.5 mg/kg every 3 weeks for 8 cycles. Results: 33 pts were enrolled. 26 male: 7 female; 13 Siewert I (39%): 20 Siewert II (61%); 21 T3N1 (64%); 10 T3N0 (30%); 2 T2N0-1 (6%). 25/33 pts went to surgery (76%), 24 had R0 resection (73%). Pathologic CR 4/33 pts (12%). 8 pts did not go to surgery: 2 for adverse events (9%, 1 CVA due to patent foramen ovale, 1 esophageal perforation due to endoscopic biopsy), 5 for progressive disease (15%). 21/24 pts (88%) received adjuvant B, 20 (95%) completed all cycles. Grade 3/4 toxicity in 30 evaluable pts during chemort: 27% neutropenia, 3% neutropenic fever, 23% esophagitis, 13% dehydration, 13% thrombocytopenia, 7% pulmonary embolism, 3% nausea/vomiting. Surgical complications: 3 anastamotic leaks (12%), 4 respiratory failure (16%), 1 pulmonary embolism (4%), 2 post op deaths (8%). At a median follow up of 20 months, PFS was 14 months and OS was 30 months. Conclusions: The addition of B to preop chemoRT in EA was tolerable without increase in treatment toxicity or surgical complications. There was no suggestion of improved pathologic CR, PFS, or OS with the addition of B to I/C/RT. Evaluation of B in phase III trials of chemort does not appear warranted. Supported by a grant from Genentech.
Retrospective cohort study on the safety and efficacy of bevacizumab for metastatic colorectal cancer patients: The HGCSG0801 study—Efficacy of KRAS mutational status.
Authors: Sogabe Susumu , Yuki Satoshi , Hayashi Hideyuki , Naruse Hirohito , Nakamura Michio , Iwanaga Ichiro , Kato Takashi , Takagi Tomofumi , Okuda Hiroyuki , Komatsu Yoshito 
Published: February 2017

680 Background: Mutations of the KRAS gene were identified as a prognostic marker in metastatic colorectal cancer(mCRC). Previously reported data suggests that the longer overall survival (OS) observed with bevacizumab(BV) treatment in mCRC is independent of alterations in the KRAS mutation status. So we analyzed efficacy of bevacizumab combined chemotherapy in mCRC relative to KRAS mutation status. Methods: In the retrospective analysis(n=212) of patients treated with BV(HGCSG0801), additional statistical analyses were done with data from KRAS mutation analyses. The Response Evaluation in Solid Tumors (RECIST) criteria version 1.0 was used to assess tumor response. The Kaplan–Meier method was used to determine Progression-free survival(PFS) and OS. Log-rank test was used to compare with mutant or wild-type KRAS in terms of PFS and OS. All statistical tests were performed using SPSS. Results: KRAS status was assessed in 88 patients (41.5%). Response rate was 58.9% with wild-type and 62.5% with mutant KRAS, that was not significant(p=0.823). The median Progression-free survival was 11.5 months with wild-type and 11.5 months with mutant KRAS, that was not significant(p=0.222). And median OS was 31.8 months with wild-type and 27.5 months with mutant KRAS, that was not significant(p=0.760) as well. Similar results were seen among patients with first-line therapy. Conclusions: Bevacizumab provides clinical benefit in patients with mCRC expressing either mutant or wild-type KRAS.
Retrospective cohort study on the safety and efficacy of cetuximab for metastatic colorectal cancer patients: HGCSG0901—Analysis of predictive markers.
Authors: Hatanaka Kazuteru , Yuki Satoshi , Nakatsumi Hiroshi , Kogawa Takahiro , Fukushima Hiraku , Fujikawa Koshi , Sato Yasushi , Saito Mayuko , Munakata Masaki , Komatsu Yoshito 
Published: February 2017

683 Background: The anti-EGFR antibody Cetuximab (Cmab) do not provide therapeutic effect to patients with KRAS mutations. It has been reported that there is no correlation between the staining intensity of EGFR and efficacy of Cmab. Moreover, the previous studies have suggested that the intensity of skin toxicity that occurs after the administration is a predictive marker of Cmab. Methods: Of 269 cases registered in the multi-institutional retrospective study (HGCSG0901) treated with Cmab, 252 patients for 3rd line or after treatment line were analyzed. Each degree of skin toxicity, KRAS mutation status and EGFR expression status, respectively, were analyzed for response rates, progression-free survival (PFS) and overall survival (OS). The Response Evaluation in Solid Tumors (RECIST) criteria version 1.0 was used to assess tumor response. The Kaplan–Meier method was used to determine PFS and OS. Log-rank test was used to compare each regimen in terms of PFS and OS. All statistical tests were performed using SPSS. Results: KRAS status: wild type (WT)/mutant type (MT): 135/32, EGFR status: positive/negative: 210/38, Skin toxicity: Grade 0/1/2/3: 31/50/128/43. Analysis of KRAS status: Response rate: WT 23.7%/MT 6.3% (p=0.028), Progression-free survival: WT 4.8 months /MT 2.1 months (p<0.001), Overall survival: WT 9.9 months/MT 5.3 months (p=0.003). There was a significant correlation between the degree of skin toxicity and efficacy. However, EGFR expression status showed no differences in efficacy. Conclusions: Here, we reported the results of efficacy analysis for each predictive marker of Cmab. As with previous reports, patients with KRAS mutations did not benefit from Cmab. Degree of skin toxicity was a useful indicator of effectiveness after starting treatment, whereas EGFR status was not effective predictor in daily practice setting.
Retrospective cohort study on the safety and efficacy of bevacizumab for metastatic colorectal cancer patients: The HGCSG0801 study—Analysis of bevacizumab beyond progression (BBP).
Authors: Fukushima Hiraku , Yuki Satoshi , Kobayashi Yoshimitsu , Hatanaka Kazuteru , Kusumi Takaya , Hosokawa Ayumu , Miyagishima Takuto , Takeuchi Satoshi , Kudo Mineo , Komatsu Yoshito 
Published: February 2017

684 Background: Bevacizumab (BV) is widely used in first-line chemotherapy for metastatic colorectal cancer in Japan, but the use of beyond bevacizumab first progression (BBP) has been controversial yet. Methods: Of patients treated with first-line BV in our retrospective cohort study (HGCSG0801), patients treated with BBP (n=22) and those without BBP ( n=19) in second-line setting were analyzed. The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used to assess adverse events. The Response Evaluation in Solid Tumors (RECIST) criteria version 1.0 was used to assess tumor response. The Kaplan–Meier method was used to determine PFS and OS. Log-rank test was used to compare each group in terms of PFS and OS. All statistical tests were performed using SPSS. Results: PS (0/1/2) before second line chemotherapy was 18/3/1 in BBP and 10/8/1 in NBBP, respectively. In the safety analysis, five patients in BBP showed a worsening/newer hypertension, which wasn’t a clinical problem. In the efficacy analysis, the response rate was 22.8% in BBP and 0% in NBBP. The median PFS was better in BBP (6.7 months in BBP and 2.7 months in NBBP), but there was no significant difference in median OS from first BV administration between two groups (27.3 months in BBP and 22.2 months in NBBP). Conclusions: We analyzed BBP in daily practice in Japan. Adverse events were well tolerated, but survival advantage of BBP was not suggested. About the efficacy of BBP, we are waiting the results of ongoing Phase III trials.
Efficacy and tolerability of bevacizumab (BEV) plus capecitabine and cisplatin (XP) in Chinese patients (pts) with locally advanced or metastatic gastric/gastroesophageal junction cancer (AGC): Results from the AVATAR study.
Authors: Shen Lin , Li Jin , Xu Jian-Ming , Pan Hong-Ming , Dai Guanghai , Qin Shukui , Wang Liwei , Wang Jinwan , Yang Zhenzhou , Yongqian Shu 
Published: February 2017

73 Background: In the AVAGAST study, chemotherapy (fluoropyrimidine and cisplatin) + BEV did not significantly improve overall survival (OS) vs. chemotherapy + placebo. Geographic differences in efficacy were observed, but only 12 Chinese pts were included. AVATAR, a study similar in design to AVAGAST, is a randomized double-blind study conducted exclusively in China in pts with AGC. Methods: Pts aged >18 years with gastric adenocarcinoma were randomized 1:1 to XP + BEV 7.5 mg/kg or placebo + XP. The primary objective was OS; secondary objectives included progression-free survival (PFS) and safety. Results: Baseline characteristics of the 202 pts were well balanced. The primary efficacy endpoint of improved OS in the BEV arm was not met (HR 1.11, 95% CI 0.79–1.56; p=0.5567; see table ). BEV + XP was well tolerated. Grade 3–5 adverse events (AEs) and serious AEs were 60% and 19% for BEV and 68% vs. 21% for placebo, respectively. Grade 3–5 AEs of special interest with BEV occurred in 8% of BEV pts and 15% of placebo pts; the difference was mainly due to grade 3–5 haemorrhage (BEV 4%, placebo 12%). Conclusions: Addition of BEV to XP in Chinese pts with AGC did not significantly improve outcomes in AVATAR. The results from AVATAR are consistent with the findings seen in the Asian sub-population of the previous AVAGAST study. [Table: see text]