bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of postoperative complications on adjuvant chemotherapy use in stage III colon cancer.
Authors: Merkow Ryan P. , Bentrem David J , Chow Warren B. , Cohen Mark E , Ko Clifford Y. , Bilimoria Karl Y. 
Published: February 2017

551 Background: The National Quality Forum has endorsed the use of adjuvant chemotherapy in stage III colon cancer yet a substantial treatment gap exists in the United States. Our objective was to evaluate the contribution of postoperative complications on the use of adjuvant therapy after colectomy for cancer. Methods: Patients from the ACS NSQIP and the NCDB who underwent colon resection for cancer were linked (2006-2008) to create a novel dataset containing robust information on comorbidities, complications, and oncologic variables. The association of complications on adjuvant chemotherapy use was assessed using multivariable regression models. Results: From 140 hospitals, 2414 patients underwent resection for stage III colon adenocarcinoma (open colectomy: 64%, laparoscopic colectomy: 36%). Overall, 896 (37.1%) patients were not treated with adjuvant therapy, of which 116 (12.9%) had documented severe comorbidities or advanced age as the reason for no adjuvant therapy receipt. Of the remaining 780 patients, 202 (25.9%) had a potential complication that could account for not receiving adjuvant therapy: 33 perioperative deaths and 169 patients with ≥1 serious complications including organ space infection (n=32), wound dehiscence (n=12), respiratory failure (n=48), pneumonia (n=45), renal failure (n=22) and septic shock (n=38). The remaining 611 patients did not have a documented reason for not receiving adjuvant chemotherapy. Complications independently associated with decreased adjuvant therapy use were renal failure (OR 0.17, 95% CI 0.0-0.59), respiratory failure (OR 0.23, 95% CI 0.11-0.51) and pneumonia (OR 0.36, 95% CI 0.18-0.75). Organ space infection was not associated with decreased use of adjuvant therapy, but significantly increased time to treatment (69 vs. 45 days, P<0.05). Superficial SSI did not decrease adjuvant therapy use or delay treatment. Conclusions: Serious postoperative complications explained one quarter of the adjuvant chemotherapy treatment gap among stage III colon cancer patients and should be considered in quality assessment of colon cancer care. Judging provider performance on quality metrics is challenging without clinical data.
Assimilation of evidence-based medicine into clinical practice: Adjuvant radiotherapy in the multidisciplinary treatment of rectal cancer.
Authors: Fitzgerald Timothy Louis , Brinkley Jason , Zervos Emmanuel E. , Wong Jan H. 
Published: February 2017

552 Background: Implementation of evidence based standards is recognized to be problematic. Level 1 evidence supports the superiority of neoadjuvant therapy for stage II/III rectal cancer. The purpose of this study was to determine to what extent evidence based medicine has impacted clinical practice. Methods: Stage II/III rectal cancer patients undergoing surgery from 1998-2007 were identified in the SEER tumor registry using SEER*Stat 6.2. Variables were extracted and analyzed in SPSS; trends were evaluated with regression models and survival with log rank test. Results: A total of 25,129 patients were identified, 15,769 (63%) were treated with adjuvant radiotherapy. A majority were > 60 years old (56%), white (82.8%), male (60.9%), had stage III cancers (59.2%) and treated with neoadjuvant radiotherapy (54.5%). Significant changes in timing of adjuvant radiotherapy were noted over the study period. In 1998 28.1% of patients were treated neoadjuvantly, this increased to 74% in 2007, a 263% increase. Scatter plot best fit lines intersect in approximately year 2002, p value of trend <0.001. On univarate analysis race (p=0.018), sex (p<0.001), year of diagnosis (p<0.001), age (p<0.001), and stage (p<0.001) were associated increased likelihood of neoadjuvant radiotherapy. Logistic regression found male sex (OR 1.14, p<0.001), year (OR 1.223, p<0.001) and stage II (OR 1.39, p<0.001) were predictors of neoadjuvant therapy. Significant increases in preoperative radiotherapy were observed for all races and cancer stages (p<0.001). There was a significant survival advantage for those treated with adjuvant radiotherapy, median survival 39 vs. 93 months p<0.0001. There, however, was no survival advantage to neoadjuvant vs. postoperative radiotherapy, median survival 94 vs. 93 months, p=0.749. Conclusions: When adjuvant radiotherapy is utilized, there has been rapid adoption of evidence based standards for Stage II/III rectal cancer. However, substantial numbers of patients are not receiving care recognized to improve outcomes.
Factors associated with delayed time to adjuvant chemotherapy (AC) in stage III colon cancer: British Columbia Cancer Agency (BCCA) cohort experience.
Authors: Chan Angela , Woods Ryan , Gill Sharlene 
Published: February 2017

574 Background: The current standard for resected stage 3 colon cancer after surgical resection is adjuvant 5FU-based chemotherapy. In trials, AC is mandated within 8 weeks after surgery, but outside the trial setting, up to 19% of patients do not receive treatment within 8 weeks. A recent meta-analysis confirms that AC started more than 8 weeks after surgery results in significantly decreased overall survival. Our objective was to ascertain logistical and patient factors associated with delayed AC delivery (defined as >56 days from surgery) in referred patients with resected stage 3 colon cancer. Methods: A population-based cohort of patients diagnosed with stage 3 colon cancer between January 2008 to December 2009 referred to the BCCA and treated with at least one cycle of AC were identified. Patient characteristics, and time intervals between surgery, referral, medical oncology consultation (MOC) and AC were assessed. Differences in patient characteristics and time intervals between patients were assessed using the Chi-square and Wilcoxon Rank-sum tests. Results: Median time from surgery to AC was 58 days with 54% of patients receiving AC beyond 56 days. Temporal differences were identified in all intervals between the between the timely and delayed groups (see table 1). Referral was most commonly initiated after hospital discharge. The only patient factors associated with delayed initiation included poorer ECOG status and being treated at the most urban centre within BCCA. Age, gender, comorbidity index, T stage and tumour location were not different between the groups. Conclusions: 54% of patients with stage 3 colon cancer had a delayed AC initiation. Process related delays at each step of the referral process need to be addressed including timely referral, MOC triage and addressing chemotherapy waitlists. [Table: see text]
Do cancer-specific variables improve risk-adjusted hospital quality comparisons?
Authors: Merkow Ryan P. , Kmiecik Thomas E. , Bentrem David J , Cohen Mark E , Hall Bruce L , Chow Warren B. , Ko Clifford Y. , Bilimoria Karl Y. 
Published: February 2017

585 Background: For patients undergoing surgery for cancer, it has been suggested that risk-adjustment with cancer-specific variables is needed when evaluating short-term outcomes. Our objectives were to assess the influence of cancer-related variables on postoperative complications and hospital quality comparisons. Methods: Patients from ACS NSQIP and NCDB who underwent colorectal resection for cancer were linked (2006-2008) to create a dataset containing robust information on comorbidities, complications, and oncologic variables. Three hierarchical models were developed predicting the NSQIP outcome 30-day mortality or any serious morbidity using variables from (1) NSQIP only, (2) NCDB only, and (3) a combined model using NSQIP and NCDB. Models were compared with fit statistics and hospital outlier agreement. Results: From 146 NSQIP hospitals, 11401 patients underwent a colorectal resection for cancer, of which, 1954 (17%) experienced a mortality or serious morbidity event. The first five variables selected in the NCDB-only model were Charlson comorbidity score, neoadjuvant therapy use, T stage, primary payer, and M stage (c-statistic, 0.64; AIC, 9886). The first five variables selected in the NSQIP-only model were ASA class, preop sepsis, albumin, surgical procedure, and COPD (c-statistic, 0.66; AIC, 9787). In the combined model, neoadjuvant therapy use was the only cancer-specific variable selected in the top five. The remaining variables were ASA class, preop sepsis, albumin, and wound class (c-statistic, 0.67; AIC, 9455). At the hospital-level, the NCDB-only model identified three high outliers (worse than expected) and one low outlier (better than expected). Both the NSQIP-only and combined models identified the same four high and two low outlying hospitals (kappa: 1.0), which agreed marginally with the NCDB-only model (kappa: 0.59). Conclusions: Addition of cancer-specific variables to NSQIP models slightly improved model fit; however, hospital outcome comparisons were identical. For patients with colorectal cancer undergoing resection, cancer-related factors have limited predictive ability for short-term outcomes and did not influence hospital quality comparisons.
Evaluation of the necessity of primary tumor resection for synchronous metastatic colorectal cancer.
Authors: Miyamoto Yuji , Sakamoto Yasuo , Ida Satoshi , Watanabe Masayuki , Baba Hideo 
Published: February 2017

592 Background: Recent advances in chemotherapy have improved survival in patients with metastatic colorectal cancer. Resection of primary tumor for patients with metastatic colorectal cancer remains controversial. Primary tumor with obstruction or bleeding may be recommended to resection pior to chemotherapy. In contrast, it should be considered potential complications associated with resection of primary tumor and disadvantage of the delay in chemotherapy. Here, we evaluate the needs of primary tumor resection for colorectal cancer patients with synchronous metastases. Methods: A retrospective analysis of patients with synchronous metastatic colorectal cancer treated at Kumamoto University Hospital between April, 2005 and December, 2009 was performed. We compared the survival of resected patients and non-resected patients. Results: 104 patients were identified. Sixty-four and 40 patients were included in the resected group and the non-resected group respectively. The mean follow-up time was 16.1 months. Median age was 61.9 and 64.3 years respectively. The non-resected group was more likely to have right-sided tumors (resected: 28%, non-resected: 43%). The number of patient with metastatic disease limited to the liver was similar in both group(resected: 48%, non-resected: 50%). In the resected group, 12 patients (18%) developed postoperative complications. In the nonresected group, 5 patients (12.5%) required creation of a diverting colostomy during the course of their treatment due to obstruction, and 2 patients (5%) required emergency surgical treatment for intestinal perforation due to the primary tumor. No significant difference in survival was observed between the groups, (logrank P=0.33). Median survival period was not significantly different (resected: 27.3 months, non-resected: 21.5 months, P=0.43). Conclusions: We concluded that it was not necessary to resect the primary lesion in patients with synchronous metastatic colorectal cancer when obstruction or bleeding was not found in primary lesions.
Influence of bevacizumab on early postoperative complications after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis of colorectal origin.
Authors: Eveno Clarisse , Glehen Olivier , Goéré Diane , Lukaszewicz Anne-Claire , Passot Guillaume , Elias Dominique , Pocard Marc 
Published: February 2017

601 Background: Increasingly patients with IV stage colorectal cancer received systemic chemotherapy combined with targeted therapy among which bevacizumab. In neoadjuvant situation, a delay of at least 6 weeks between discontinuation of bevacizumab and surgery is recommended, not to increase the risk of complications (delayed healing, bleeding) related to bevacizumab. The goal of this study was to analyze the potential impact of bevacizumab on early morbidity after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis of colorectal origin. Methods: From 2004 to 2010, in three hospitals, 183 patients treated with complete cytoreduction followed by HIPEC for colorectal carcinomatosis, received preoperative treatment. It was either systemic chemotherapy alone (Chemo group, n = 100) or by chemotherapy combined with bevacizumab (Beva group, n = 83). Results: Both patient groups were comparable in the extent of carcinomatosis, assessed on peritoneal cancer index means (10.4 vs 10, p> 0.05), number of resected organs (4.3 vs 3.8, p> 0.05), operative time (420 vs. 380 minutes, p> 0.05) and volume of blood loss (470 vs 510ml, p> 0.05). The median time from discontinuation of bevacizumab and HIPEC was 7 weeks (6-10), always greater than 6 weeks. Nine patients postoperatively died, 4 (4%) in the chemo group and 5 (6%) in the beva group (ns). Grade 3 to 5 complication rate was higher in the beva group (25 vs 12%, p <0.05). Whatever the hospital, complications that may be related to bevacizumab occurred more frequently in patients in the beva group: with more digestive fistulas (18 vs 8%, p <0.05), deep abscesses (13 vs 3 %, p <0.01) and delayed healing (11 vs 2%, p <0.02). Conclusions: Administration of bevacizumab before surgery with complete cytoreduction followed by HIPEC for carcinomatosis colorectal is associated with increased morbidity, probably due to multiple organ resections performed during the surgery. The oncologic benefit of bevacizumab before HIPEC remains to be evaluated.
Impact of mismatch repair (MMR) testing on colorectal cancer (CRC) oncology clinical practice.
Authors: Hewish Madeleine , Stamp Gordon , Puckey Loretto , Shanley Susan , Costello Clare , Webb Janine , Hulkki Wilson Sanna , Gonzalez de Castro David , Barbachano Yolanda , Saffery Claire , Swanton Charles , Lord Christopher J. , Reis-Filho Jorge S. , Ashworth Alan , Chau Ian , Cunningham David 
Published: February 2017

603 Background: MMR deficiency (dMMR) has been reported in 15% of CRC, but with a lower frequency in advanced disease. Most cases are due to sporadic MLH1 promoter hypermethylation (often with BRAF mutations), with a minority reflecting germline mutations in MLH1, MSH2, PMS2, or MSH6 (Lynch Syndrome [LS]). The Revised Bethesda Guidelines (RBG) are one means of selecting individuals at risk of LS for further assessment, but will miss a proportion of cases. Methods: We screened all consenting patients for eligibility for CRC trials recruiting specific genetic aberrations, which included MMR assessment. Results: Of 314 patients, immunohistochemistry (IHC) for MMR protein expression is complete on 171. Staining was reduced/absent in 19.3% of tests, and heterogeneous in 12.1%. The dMMR rate was 6.4%. 2 dMMR patients* were identified as at risk of LS, and referred to genetics by their treating clinician before IHC results were known. However 4 other cases† were not referred, and an underlying predisposition would have been missed without this unbiased approach. 4 patients developed metastatic disease, with none experiencing a partial response to chemotherapy thus far. (Table.) Conclusions: This data is representative of a practice with a high proportion of metastatic disease. It suggests that within oncology, an unbiased screening approach for LS is preferable. Whilst the RBG detect the majority of cases, they may be underutilised as other management issues take precedence in oncology clinics. A cost-effective alternative may be the introduction of a nurse-led programme to identify cases at risk, as is being introduced at our centre. A spectrum of clinical behavior exists amongst metastatic dMMR CRC, and larger numbers will reveal if this affects therapeutic response. [Table: see text]
IXOA regimen, irinotecan (I), capecitabine (X), oxaliplatin (O), and bevacizumab (A), as first-line therapy for advanced unresectable colorectal cancer (aCRC): Preliminary results.
Authors: Maroun Jean Alfred , Jonker Derek J. , Cripps M. Christine , Goel Rakesh , Asmis Timothy R. , Goodwin Rachel Anne , Yarom Nirit , Marginean Horia 
Published: February 2017

604 Background: IXO showed acceptable toxicities and promising efficacy in a phase I/II study as 1st-line therapy for aCRC patients (pts). Combination with A might enhance the efficacy of IXO treatment. Methods: The objectives of the study were to evaluate the recommended dose (RD) of IXO regimen when used in combination with A (IXO+A), and to document safety and efficacy of the combination. Starting dose was: I 160mg/m2 IV d1, X 950mg/m2 bid PO d2-15, O 100mg/m2 IV d1, A 7.5 mg/kg iv d1, q3w. IXO regimen dose adjustments were planned in case of therapy-attributed severe toxicities. Results: 23 pts enrolled and evaluable for toxicity, 16M/7F, median age 65 years (range 28-77), PS 0/1/2 in 7/16/0, sites of disease (colon 18/rectum 5) received 288 cycles, median 8 (range 1-40). Gr.4 neutropenia and thromboembolic toxicity in the first 6 pts induced a 15% I and 20% X dose reduction, followed by another 10% I dose reduction in the following 6 pts due to diarrhea and febrile neutropenia. The adjusted regimen with reduced I 25% and X 20% from initial IXO, was considered safe for cohort expansion. Overall Gr.3+ toxicity included: 35% neutropenia, 4% febrile neutropenia, 13% leucopenia, 4% thrombopenia, 7% thromboembolic events, 44% diarrhea, 22% nausea and vomiting, 22% fatigue, 17% dehydration. Two treatment-related deaths (MI and pancolitis) were observed. Among 18 evaluable pts (2 NE, 3 too early for evaluation) response was 12 PR (up to 37 months), 5 SD and one DP. At a median follow-up of 16.5 months, 7 pts have progressed after median 15 months (range 2.5-32.1). Median PFS and OS were not reached. Conclusions: The IXO+A combination required I and X dose adjustment as compared with the initial IXO regimen, with diarrhea, neutropenia and thromboembolic events being the main toxicities. Recruitment continues in an expanded cohort at the newly identified phase II RD: I 125mg/m2, X 750mg/m2, O 100mg/m2, A 7.5 mg/kg. IXO+A shows promising efficacy and acceptable toxicity. Supported by Roche Canada.
Number of lymph nodes recovered as an independent prognostic factor in predicting outcome in patients with pathologically node-negative rectal cancer following preoperative chemo/radiotherapy.
Authors: Rodda Sree Lakshmi , Dhadda Amandeep Singh , Dickinson Peter D. , Zaitoun Abed M , Bessell Eric M 
Published: February 2017

606 Background: To determine the importance of number of lymph nodes recovered on outcome in pathological node negative rectal cancer patients who had received chemo/radiotherapy prior to surgery. Methods: We retrospectively analysed data from 262 patients with locally advanced rectal cancer who received pre-operative chemo/radiotherapy at Castle Hill Hospital, Cottingham and Nottingham University Hospital between 2001 and 2008. Patients were treated with CT planned radiotherapy to a dose of 45-50 Gy in 25 fractions with concurrent fluoropyrimidine chemotherapy. Surgery was normally performed at an interval of 6-8 weeks. There were 152 patients who were found to be pathologically node negative for further analysis. Median follow-up was 51.5 months Patients were grouped into < 10 nodes recovered or > 10 nodes recovered. Disease free survival (DFS) and overall survival (OS) was assessed using Log rank test. Multivariate analysis was performed using Cox-regression analysis. Results: Of the 152 patients analysed, 67.1 % (n=102 ) had fewer than 10 nodes recovered and 32.8% (n=50) had greater than 10 nodes recovered. The median number of nodes recovered was 7 (range 0-39). There was a improvement in 5 year DFS and OS in group who had more than 10 nodes recovered compared to group with less than 10 nodes recovered ( DFS at 5yrs :86.5% vs. 61.5%, p=0.01, OS at 5 yrs : 77.8% vs. 67.4% , P =0.059). On multivariate analysis pathological T-stage , circumferential resection margin (CRM) status and number of lymph nodes recovered were found to be independent predictors of disease free survival (p=0.002). Conclusions: The number of lymph nodes retrieved following surgery for locally advanced rectal cancer patients following chemo/radiotherapy is an independent prognostic factor in pathologically node negative patients. This may need to be considered when making subsequent adjuvant chemotherapy decisions.
Accuracy of computed tomography in staging colon cancer patients.
Authors: Oxner Christopher Ryan , Nelson Rebecca A. , Lee Wendy , Duldulao Marjun Philip , Wiatrek Rebecca Lynn , Chen Steven , Pigazzi Alessio , Kim Joseph , Garcia-Aguilar Julio 
Published: February 2017

614 Background: Though adjuvant chemotherapy is well-established for treating patients with AJCC Stage III colon cancer, there is growing interest in giving chemotherapy neoadjuvantly for these patients. Since clinical staging to determine eligibility requires accurate preoperative imaging, our objective was to determine whether computed tomography (CT) scans can be used to detect nodal disease in colon cancer patients. Methods: We identified patients with AJCC stage I-III colon cancer who underwent curative resection between 2006 and 2010 at our institution. Patient CT scans were obtained and final radiologic reports were recorded in a database. CT images underwent secondary prospective review by a blinded independent surgeon with the intent to identify mesenteric lymphadenopathy (N+). Clinical staging from the original radiologic report and secondary surgeon review of the CT images were then compared with pathologic staging. Results: Imaging and pathology were available for 67 colon cancer patients. Original radiologic review reported N+ disease in 10 of 67 patients (15%), but final pathology revealed 31 of 67 (46%) patients to be N+. Therefore, radiological review correctly predicted Stage III disease in 10 of 31 (32%) patients. On final pathology, 36 of 67 (54%) patients had no nodal disease (N0). Radiologic reports noted absence of lymphadenopathy in 29 of 67 (43%) patients, thus accurately predicting N0 disease in 29 of 36 (80%) patients. Of 67 studies, 14 (21%) had no mention of lymphadenopathy and were considered N0. Of these 14, 6 were N+ on final pathology. Surgeon review accurately identified N+ disease in 4 of these 6 patients. On surgeon review, sensitivity increased from 32% to 68% while specificity dropped from 80% to 61%, corresponding to a decrease in false negatives from 68% to 32% and an increase in false positives from 20% to 39%. Conclusions: Current clinical staging of colon cancer by CT has low accuracy. However, actively seeking nodal disease improves sensitivity but with minor loss of specificity. Improved radiologic criteria and technology may further increase accuracy in clinical staging of Stage III colon cancer patients who will receive neoadjuvant treatment.