bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time to adjuvant chemotherapy (TTAC) after open or laparoscopic resection surgeries in colorectal cancers (CRC).
Authors: Miller Selene A. , Sevick Laura , Acuna Sergio , Mercado Marck , Baxter Nancy N. , Burnstein Marcus J. , De Montbrun Sandra , Rotstein Ori D. , Tang Grace , Varatheswaran Winthya , Brezden-Masley Christine 
Published: February 2017

768 Background: This single institution retrospective study evaluates the reason for delay in Time To Adjuvant Chemotherapy (TTAC) from curative resection surgery to start of adjuvant therapy in CRC. The reason for this study was to determine if type of surgery (laparoscopic versus open) increased TTAC of which evidence indicates poorer disease free survival and overall survival (Biagi J, Raphael M, Mackillop W, Kong W, King W, Booth C. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA, 305(22):2335-42. doi: 10.1001/jama.2011.749.) Methods: CRC patients treated at St. Michael’s Hospital in Toronto, Canada were included if diagnosed with stage II or III disease, underwent curative resection surgery between January 1, 2006, and December 31, 2012, and either received systemic adjuvant chemotherapy or surveillance protocol. Results: Among 259 patients, 92 patients (35.7%) underwent curative laparoscopic resection and 166 open resection (64.3%). Intraoperative and/or postoperative complications were experienced in 73 patients. Complications were less prevalent among patients who underwent laparoscopic surgery versus open resection (11.9% vs. 36.8%; p<0.0001). Of these 73 complications, wound infection (39.7%), intraoperative procedural complication (14.3%), and postoperative gastrointestinal complications (6.4%) were most prevalent. After adjusting for complication and clustering within the operating surgeon, there were no statistical differences in TTAC between open (51.310 ± 1.7 days) and laparoscopic (49.2 ± 1.6 days) resection surgeries (p=0.1996). However, presence of a complication was associated with delay in TTAC (HR 0.501; 95% CI, 0.43-0.58; p<0.001). Conclusions: TTAC in CRC patients does not differ statically for each type of resection surgery. However, presence of a complication is associated with delays in TTAC and is over three-fold more prevalent in open than laparoscopic resections. Therefore, there is an increased risk of delay in TTAC for open resection surgeries than laparoscopic resections due to a higher prevalence of surgical complications.
Effect of dementia diagnosis on receipt of postoperative colon cancer chemotherapy.
Authors: Chen Yingjia , Semrad Thomas John , Cress Rosemary Donaldson , Beckett Laurel A. 
Published: February 2017

769 Background: Colon cancer and dementia have a high risk of co-occurrence. Prior studies found that patients with dementia have higher mortality than non-demented counterparts, mostly from non-cancer causes. We hypothesized that a dementia diagnosis using an improved algorithm would be associated with reduced use of postoperative therapy. Methods: In addition to the claims-based algorithm for dementia published by Centers for Medicare and Medicaid Services that uses SEER-Medicare Medicare Provider Analysis and Review, Carrier Claims, Home Health Agencies, and Outpatient files, we developed a medication-based algorithm using the part D file based on prescription for any of the five FDA-approved dementia drugs (donepezil, galantamine, memantine, rivastigmine, tacrine). We measured agreement between the two diagnostic algorithms with k-statistics. Using each algorithm and a final combined algorithm, we used multivariable logistic regression adjusting for demographics and disease characteristics to examine the effect of dementia on the use of post-operative colon cancer chemotherapy. Parallel analyses restricted the population to later-stage cancer patients (stage III/IV). Results: 46,126 patients diagnosed between 2007 and 2009 were identified. 20% had dementia by either of the algorithms. 9% of the dementia cases were identified through Part D data. The two algorithms showed moderate agreement (k>0.49, p=0.007). After surgery, those patients with dementia by the combined algorithm were less likely to receive chemotherapy (OR = 0.641, 95% CI: 0.597-0.688). Those with dementia identified by part D data were even less likely to receive chemotherapy than those identified by the claims algorithm (OR=0.617, 95% CI: 0.466-0.816 for medication; OR=0.767, 95% CI: 0.684-0.860 for claims). A similar pattern was detected when restricting to stage III/IV patients (OR=0.667, 95% CI: 0.457-0.973). Conclusions: Part D data increases the sensitivity for identifying dementia cases in SEER-Medicare. Patients with dementia are significantly less likely to receive post-operative chemotherapy. Thus, reduced postoperative colon cancer therapy among patients with dementia may contribute to higher cancer-related mortality.
Prophylactic use of oral dexamethasone (DEX) to alleviate fatigue during regorafenib (REG) treatment for patients with advanced colorectal cancer (aCRC).
Authors: Fukuoka Shota , Shitara Kohei , Noguchi Masaaki , Kawazoe Akihito , Kuboki Yasutoshi , Bando Hideaki , Okamoto Wataru , Kojima Takashi , Doi Toshihiko , Ohtsu Atsushi , Yoshino Takayuki 
Published: February 2017

774 Background: Regorafenib (REG) is an oral multi-kinase inhibitor which demonstrated significant overall survival (OS) benefit for patient with advanced colorectal cancer (aCRC). Fatigue is the most common toxicity in all grade associated toxicity with REG, which is one of major reasons for early dose modification. On the other hand, recent study suggested that dexamethasone (DEX) improve the cancer associated fatigue. Methods: We retrospectively analyzed the effect of prophylactic use of oral DEX on fatigue during REG treatment for patients with aCRC. Ninety-three patients who received REG in our institution between May 2013 and June 2014 were divided into two groups according to use of oral DEX (2 mg per day; by investigator’s discretion). Outcomes measured in this study were a time to dose modification, incidences of toxicities, and anti-tumor effects. Results: Prophylactic DEX was administrated in 24 patients (DEX group) with regorafenib, and 69 patients received REG alone (no DEX). There were no significant differences in baselinepatient characteristics between 2 groups including starting dose of REG (79.1% in DEX and 84.1% in no DEX started with 160 mg/day). Time to dose modification was significantly longer in DEX than in no DEX (15 vs. 9 days; p=0.009). Incidence of fatigue (grade>1) was lower in DEX (25%) than no DEX (43%) by 18%, although the difference was not statistically significant (p=0.11). Fewer patients experienced decreased appetite (grade>1) with DEX than no DEX (4.2 vs. 33.3%; p=0.005) as well as hand foot skin reaction (grade>3; 0 vs. 27.5%, p=0.02). In contrast, the frequency of oral candidiasis, which was improved within 1 week, was higher in DEX group (14.3% and 0%; p=0.001). Disease control rate (45.8 vs. 36.2%), progression-free survival (median, 2.1 vs. 1.8 months) and OS (median, 7.6 vs. 6.0 months) were almost compatible between DEX group and no DEX. Conclusions: Although the incidence of fatigue was not significantly decreased by use of DEX, it prolonged time to dose modification of REG in our preliminary analysis. Decreased incidence of appetite loss and HFSR also suggest that concurrent DEX with REG warrants further investigation.
Efficacy and safety of capecitabine plus oxaliplatin (XELOX) as the perioperative treatment of patients with potentially resectable liver-only metastases from colorectal cancer: A single arm, open-label, multicenter phase II trial (ML22298; NCT00997685).
Authors: Lin Feng , Li Guoxin , Chu Zhonghua , Hao Chunyi , Chen Mingqing , Jiang Zhiwei , Chen Huanqiu , Lin Jianjiang , Li Dechuan , Hu Bing , Wang Xishan 
Published: February 2017

777 Background: Surgical resection can improve survival of patients with resectable colorectal liver metastases (CLMs). Here, we investigatedthe efficacy and safety of XELOX as perioperative treatment for patients with potentially resectable CLM. Methods: Patients with potentially resectable liver-only metastases from CRC were enrolled. The primary endpoint of this study was progression-free survival (PFS); and the secondary endpoints included objective response rate (ORR), R0 resection rate, overall survival (OS) and safety profile of perioperative treatment of XELOX. Eligible patients were treated with XELOX (oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1,000 mg/m2 b.i.d. for 14 days every 3 weeks). Tumor remission was assessed by CT after 6 weeks (2 cycles) of chemotherapy. Resectability of CLM was assessed by CT after 12 weeks (4 cycles) of chemotherapy. Adjuvant chemotherapy using XELOX was started within 8 weeks after hepatectomy. Results: Thirty patients (17 males and 13 females) were enrolled from 10 medical sites between January 2010 and October 2011, with median age of 57.5 years (range: 32-77). Median PFS was 336 days (95% CI: 173~385), and median OS was 912 days (95% CI: 516~1332). The ORR was 40% (12/30). The conversion rate from unresectable to resectable was 43.3% (13/30). Among these 11 patients who had received surgery (2 had withdrawn consent), 10 (90.9%) had received R0 resection. Subgroup analysis shows that patients who had received hepatectomy had longer median PFS [95% CI] (382 days [210~518] vs. 173 days [111~337], p = 0.0268) and median OS [95% CI] (1332 [721~NA] vs. 516 [295~1046], p = 0.005). There were 4 patients with post-operation complications of ascites and/or hydrothorax, and 3 patients had early chemotherapy termination due to drug-related AEs, including leukopenia, hepatotoxicity and diarrhea. Conclusions: Perioperative chemotherapy of XELOX is an option for patients with potentially resectable CLM due to the effect in prolonging PFS and OS, as well as the manageable toxicities and post-operation complications. Clinical trial information: NCT00997685.
Management tips for the low incidence, of adverse events and well efficacy of regorafenib for metastatic colorectal cancer in Juntendo University Medical Hospital.
Authors: Higashihara Yoshie , Serizawa Nobuko , Kato Junko , Kodani Tomohiro , Osada Taro , Nagahara Akihito , Watanabe Sumio 
Published: February 2017

778 Background: Regorafenib is an oral multi-kinase inhibitor that has demonstrated significant overall survival for metastatic colorectal cancer in CORRECT study. In the Japanese subset of CORRECT study, adverse events (AEs) such as hand-foot skin reaction (HFSR), anorexia, and liver dysfunction occurred at high frequency. Therefore, those AEs were one of the causes for treatment discontinuation. Methods: We retrospectively analyzed the safety and efficacy in 14 patients who received regorafenib monotherapy in our hospital between June 2013 and August 2014. Results: Among the 14 patients, median age was 64.5 years old (range 53-76). Median follows up time was 209 days (range 72-340), median PFS was 64 days (range 19-272), and median TTF was 66.5 days (range 18-280). There was no patient who had complete or partial response. The disease control rate was 36%. Nine patients initiated with 160 mg of regorafenib once daily, 4 patients with 120 mg, and one patient with 80 mg. The most common grade 3 or more AEs were HFSR, AST and ALT elevations and hypertension (2 patients, 14.2%, respectively). The frequency of HFSR was lower in our cohort the Japanese patients of CORRECT study. Treatment discontinuation due to drug related AEs occurred to 5 patients (35.7%). Dose reduction and interruption of regorafenib were required in 10 patients (71.4%) and 8 patients (57.1%), respectively. For prevention of HFSR, more than 90% of the patients were received proactive treatment including heparinoid and strong steroid from the start of the therapy. We carefully monitored their toxicities every week during the first cycle, and chose interruption if patients were had more grade 2 AEs. It is very important, we think to give the patients instructions on possible AEs and how to manage them using an illustrated book. Conclusions: Our cohort had lower HFSR in frequency than and similar efficacy to the Japanese subpopulation in CORRECT study. Enough explanation and instruction to patients might be important to decrease an incidence of AEs and treatment discontinuation due to drug- related AEs. We will increase the number of cases and examine in future.
Strategy for cStage4 colorectal cancer: Chemotherapy or resection of primary tumor?
Authors: Iwamoto Shigeyoshi , Hamada Madoka , Oishi Masaharu , Sakaguchi Tatsuma , Michiura Taku , Inoue Kentaro , Kwon A-Hon 
Published: February 2017

779 Background: It is controversial that the primary tumor must be removed prior chemotherapy in cStage4 colorectal cancer, because some cases prognostic factor were metastatic sites. We report cases of cStage4 colorectal cancer which were underwent intrensive chemotherapy prior the primary tumor resection. Methods: 190 cases of metastatic colorectal cancer were treated by L-OHP based chemotherapy plus bevacizumab/cetuximab/panitumumab in September 2007 to June 2012. 56 cases were treated by intensive chemotherapy prior primary tumor resection, and 44 cases were underwent surgical resection of primary tumor after evaluation of chemotherapy response. Results: 38/10/8 cases were treated by bevacizumab/cetuximab/panitumumab with L-OHP combined therapy as intensive treatment. 30 patient with obstructed primary lesion were underwent stoma surgery (53.6%). Evaluable lesions except primary lesion were liver (50.0%), lung (12.5%), LNs (33.9%). Response rate of chemotherapy were 67.9% (PR/NC/PD: 38/14/4), and 44 cases were performed resection of primary lesion in PR and SD cases. Pathological G2 and G3 response in resected primary lesion were 18.4% (G1a/G1b/G2/G3:17/18/8/2). A GI perforation and bowel obstruction in chemotherapy and 3 cases of anastomotic leakage and 6 cases of SSI in perioperable period were observed respectively. Conclusions: It is seemed to contribute improvement of QOL and local control that start with systemic chemotherapy prior primary lesion resection, therefore some cStage4 cases were difficult to R0 resection also primary lesion and systemic chemotherapy could be reduced symptom with metastatic sites. Only 18.4% of the resected primary tumor were G2/3 pathological response by systemic chemotherapy, on the other hand preoperative chemo-radiation in rectal cancer accomplished 67.3% of G2/3 pathological response (in house data). The end-point of therapy in stage 4 colorectal cancer patient are QOL and prolong survival, and should be selected treatments depending on the patient condition.
Analysis of the GERCOR index in KRAS Exon2 WT patients with mCRC treated with salvage-line cetuximab-based chemotherapy: HGCSG0901.
Authors: Hosokawa Ayumu , Yuki Satoshi , Nakatsumi Hiroshi , Hatanaka Kazuteru , Tsuji Yasushi , Okuda Hiroyuki , Takahashi Yasuo , Konno Jun , Eto Kazunori , Kawamoto Yasuyuki , Sonoda Norikazu , Sato Yasushi , Saito Mayuko , Miyagishima Takuto , Ikeda Shinichiro , Yoshizaki Koji , Sasaki Takahide , Saitoh Soh , Sakata Yuh , Komatsu Yoshito 
Published: February 2017

781 Background: The GERCOR index (GI) based on performance status and serum LDH was reported to be useful to predict survival for patients with previously untreated mCRC. However, in the salvage setting, the validity of the GI has not been reported in patients treated with cetuximab (Cmab)-based chemotherapy. Methods: 269 patients with mCRC treated with Cmab contained chemotherapy were retrospectively registered from 27 centers in Japan. This analysis was included in the KRAS Exon2 wild type patients who were refractory to or intolerant of 5-FU / irinotecan/ oxaliplatin and were never administered anti-EGFR-antibody. Univariate and multivariate analysis for overall survival (OS) were performed using patient characteristics. Survival analyses were performed with the Kaplan-Meier method, log-rank test and the Cox proportional hazards model. The analysis was also designed to determine whether the GERCOR index could be extended to progression-free survival (PFS). Results: All data were available for prognostic categorization in 132 patients. Median OS and PFS were 9.8 and 4.3 months. The distribution and median OS / PFS for GI were as follows: low risk (L)(n = 28; 17.9/3.8 months), intermediate risk (I)(n = 52; 12.2/5.0 months), and high risk (H)(n = 52; 7.5/4.1 months). For OS, there was significant difference between L and H (p < 0.001) and between I and H (p < 0.001), but not between L and I (p = 0.076). For PFS, there was significant difference between I and H (p = 0.017), but not between L and I (p = 0.407), and between L and H (p = 0.222). In the Cox multivariate analysis, GI showed an independent prognostic impact (L vs. I ; HR 2.195, p=0.003 / L vs. H ; HR 4.028, p<0.001), but not predictive impact (L vs. I ; HR 0.987, p=0.958 / L vs. H ; HR 1.314, p=0.268). Conclusions: In this analysis, GI might be a prognostic factor in salvage treatment with Cmab-based chemotherapy.
Factors affecting chemotherapy use and delay (≥ 8 weeks) after colorectal cancer surgery and the impact of chemotherapy delay on survival.
Authors: Kim Ik Yong , Kim Young Wan 
Published: February 2017

784 Background: To date, reasons for adjuvant chemotherapy (AC) omission and delay have not been extensively studies. This study aimed to evaluate factors affecting chemotherapy use and delay (≥8 weeks) after colorectal cancer surgery and their impact on survival. Methods: Between 2008 and 2013, consecutive 584 patients undergoing major resection for stage II and III colorectal cancer in a single tertiary referral center. Results: Among 584 patients with stage II and III diseases, AC was performed in 460 (78.8%) patients. Regimens included fluorouracil with folinic acid (n=257, 55.9%), FOLFOX (n=134, 29.1%), capecitabline (n=62, 13.5%), and tegafur-uracil (n=7, 1.5%). Factors affecting not receiving AC were older age (>80 years), American Society of Anesthesiologists score (≥3), presence of postoperative complication, and not receiving preoperative chemoradiation. Overall survival was 87.2% (AC +) and 58.5% (no AC, p<0.001) in stage II disease, and 79.5% (AC +) and 24.6% (no AC, p<0.001) in stage III disease, respectively. Recurrence-free survival was 83.7% (AC +) and 61.9% (no AC, p=0.003) in stage II disease, and 60.5%(AC +) and 21.8% (no AC, p<0.001) in stage III disease, respectively. Among 460 patients undergoing AC, AC was initiated within 8 weeks in 438 patients (95.2%) and after 8 weeks in 22 patients (4.8%). Factors affecting AC delay were male gender, rectal primary, intraoperative blood loss (>100ml), and presence of postoperative complications. Overall survival was 90.8% (AC +) and 40.0% (no AC, p=0.111) in stage II disease, and 82% (AC +) and 35.6% (no AC, p=0.275) in stage III disease, respectively. Recurrence-free survival 80.1% (AC +) and 54.5% (no AC, p=0.133) in stage II disease, and 64.4% (AC +) and 0.0% (no AC, p=0.014), respectively. Conclusions: In stage II, III patients, it appears that use of AC is more closely related patient’s survival rather than the time of AC initiation. To improve oncologic outcomes after curative resection, it is important to increase the proporation of AC use.
Oxaliplatin rechallenge in patients with metastatic colorectal cancer prior treatment with oxaliplatin.
Authors: Kim Jeong-Eun , Hong Yong Sang , Kim Kyu-Pyo , Park Seong Joon , Lee Jae-Lyun , Kim Tae Won 
Published: February 2017

785 Background: With limited number of available cytotoxic agents for the treatment of metastatic colorectal cancer (mCRC) patients (pts), rechallenge of chemotherapy can be considered for continuum of treatment. We investigated the efficacy and feasibility of oxaliplatin rechallenge in mCRC pts who have been already exposed to prior oxaliplatin-based chemotherapy. Methods: mCRC pts, who were re-treated with oxaliplatin-based chemotherapy as second or later line treatment in the presence of evaluable disease, were retrospectively accrued. Only those who remained disease-free or progression-free at least 6 months after the last dose of prior oxaliplatin were included. Results: Between January 2009 and May 2014, 110 pts were retreated with oxaliplatin-based regimen; 42 (38.2%) patients received prior oxaliplatin as adjuvant chemotherapy and 68 (61.8%) as palliative chemotherapy. Median disease-free or progression-free duration after prior oxaliplatin was 15.4 months (range, 12.9-17.6 months). All of them received oxaliplatin rechallenge in combination with fluoropyrimidines. The overall response rate to the oxaliplatin rechallenge was 30.9% (34/110), and the disease-control rate was 68.2% (75/110) with 1 complete response, 33 partial responses, and 41 stable diseases. Median progression-free survival and overall survival with rechallenge of oxaliplatin-based therapy were 5.9 months (95% CI, 4.6-7.2 months) and 19.7 months (95% CI, 11.9-27.5 months), respectively. Grade 2 or 3 neuropathy was observed in 16 patients. Any grade hypersensitivity reaction was observed in 10 patients within 4 cycle of treatment. Among them, 6 patients stopped treatment due to grade 3 or 4 hypersensitivity reaction. Conclusions: Rechallenge of oxaliplatin-based therapy could be a treatment option in patients who achieved at least 6 months of disease-free or progression-free survival with prior oxaliplatin-based chemotherapy, especially in those who have lack of further treatment option with good performance status. However, neurotoxicity and hypersensitivity reaction should be cautiously monitored in this setting.
Identification of the gastric microbiome from endoscopic biopsy samples using whole genome sequencing.
Authors: Zhang Chao , Cleveland Kyle , Schnoll-Sussman Felice , McClure Bridget , Bigg Michelle , Thakkar Prashant , Schultz Nikolaus , Pamer Eric G. , Betel Doron , Shah Manish A. 
Published: February 2017

8 Background: H. pylori is the primary risk factor for gastric cancer (GC). However, virtually all infected patients do not develop GC, and H. pylori eradication does not reduce GC risk. We established a whole genome sequencing (WGS) pipeline to detect the gastric microbiome from small endoscopic samples directly. With it, we are not only be able to accurately detect H. pylori infection in GC, but also examine the microbiome in samples from other malignancies. Methods: Patients (pts) undergoing upper endoscopy without chronic inflammatory disease or chronic NSAID use were eligible for participation, categorized as follows: (1) active infection (H. pylori identified on biopsy, or positive CLOtest), (2) prior infection (previous H. pylori treatment, or ELISA IgG positive), and (3) gastric cancer. Endoscopic biopsies from 3 locations in the antrum/body were freshly frozen for WGS on a HiSeq2500 platform at ~10X coverage. Our customized computational pipeline successively removes human sequences, with remaining un-mapped reads aligned to 1,400 unique bacteria genomes. Results: 16 biopsy samples taken from 10 pts were sequenced. All H. pylori positive samples detected by our pipeline have been successfully validated by qPCR. Surprisingly, H. pylori was identified in previously treated pts. We also applied our pipeline to control samples to evaluate the performance of bacterial identification. Negative sample are blood samples from HapMap projects with human DNA only. In contrast, positive samples are bacteria enriched samples from Human Microbiome Project. Our identifications matched the previously reported results. Finally, we profiled 37 gastric cancer tumors and matching normal WGS samples from TCGA and found that 40% of them are H. pylori positive. This result is a novel discovery that was not reported in the TCGA GC study. Conclusions: This is the first demonstration of detailed unbiased microbiome detection performed from gastric endoscopic biopsy samples using WGS. We found that standard treatment does not always eradicate H. pylori possibly explaining why H. pylori treatment fails to reduce cancer risk. We also found that ~40% of gastric cancers have evidence of persistent H. pylori bacterial content.