bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of preoperative dexamethasone on the postoperative systemic inflammatory response and complications following surgery for colorectal cancer.
Authors: McSorley Stephen Thomas , Horgan Paul G. , McMillan Donald C
Published: February 2017

692

Background: It is now clear that there is a significant association between the magnitude of the systemic inflammatory response and postoperative complications (Adamina et al. Br J Surg 2015;102(6):590-8). The present study examined the impact of preoperative steroids on the postoperative systemic inflammatory response and complications, following elective surgery for colorectal cancer. Methods: The administration of dexamethasone at induction of anaesthesia was prospectively audited from a cohort of patients who underwent elective, potentially curative surgery for colorectal cancer at a single centre between 2008 and 2013. Results: 286 patients were included, of which the majority were male (161, 57%), over 65 (190, 66%) with colonic (183, 64%) and node negative disease (192, 67%). 114 (40%) received dexamethasone at induction of anaesthesia. There was a significant association (Table 1) between preoperative dexamethasone administration and the proportion of patients breaching established CRP thresholds on postoperative days 2 (190mg/L, 14% vs. 50%, p<0.001), and 3 (170mg/L, 27% vs. 49%, p<0.001) but not 4 (145mg/L, 50% vs. 36%, p=0.658). There was no significant association between preoperative dexamethasone and postoperative complications. Conclusions: The present study suggests that the systemic inflammatory response following surgery for colorectal cancer may be attenuated by preoperative steroids. It remains to be determined whether this will lead to a reduction in postoperative complications. [Table: see text]
Colorectal liver metastases management in the Veterans Health Administration: Geographic disparity.
Authors: Mobarek Dalia A. , Visser Brendan C. , Krasnow Steven , Chang Ji Won , Nechodom Patricia , DuVall Scott L.
Published: February 2017

694

Background: Multidisciplinary management including surgical resection of Colorectal Liver Metastases (CLM) offers the greatest chance of long-term survival. We aimed to study surgical intervention types, rates and factors affecting the decision making in the Veterans Health Administration. Methods: The Veterans Affairs Central Cancer Registry (VACCR) and VA Informatics & Computing Infrastructure (VINCI) were queried and linked to retrospectively analyze stage IV CLM from 10/01/2004-12/31/2012. Cohort construction and statistical analyses were performed utilizing SQL Server, SAS software, version 9.4 (SAS Institute Inc., Cary, NC) and Microsoft Excel. Results: We identified 118 VA stations and 1245 subjects meeting the inclusion criteria. Hemicolectomy was identified in 79%, (637) and 21 % (168) liver metastatectomy. Open versus laparoscopic hemicolectomy was 87.96% and 12.04% respectively. Follow-up imaging post metastatic disease diagnosis was carried in 88.9% (1,108) subjects. Immense variation in the percentage of surgeries conducted and the sites of surgery when stratified by geographic location. The percentage of patients receiving surgery at the colon remained high across almost all the stations. In 53 stations, hemicolectomy and hepatectomy were attempted in at least 15% of subjects with stage IV colorectal cancer and isolated liver metastases. Of the high volume stations, only 52% had a 15% or higher percentage of hemicolectomy and hepatectomy. Subjects receiving hepatectomy only were the least frequent and occurred in only three stations. Age at diagnosis, gender, Charlson comorbidity scores and the performance status at diagnosis did not differ significantly among surgery versus no-surgery groups. Conclusions: Geographic disparity emerged as a factor affecting metastatectomy decisions. Ongoing analysis to identify and analyze the differences amongst various stations is underway. Additional characterization of the liver metastases including size, number, and specific hepatic lobe and the surgical expertise is underway.
Use and impact of bevacizumab in patients undergoing liver resection for metastatic colorectal cancer in routine clinical practice.
Authors: Kwan Edmond Michael , Lee Belinda , Wong Hui-Li , Lee Margaret , Wong Rachel , Shapiro Jeremy David , Burge Matthew E. , Lipton Lara Rachel , Kosmider Suzanne , Gibbs Peter
Published: February 2017

698

Background: In metastatic colorectal cancer (mCRC) patients with isolated liver metastases, surgical resection offers the greatest likelihood of cure. Whilst for mCRC patients treated with palliative intent the addition of bevacizumab to the chemotherapy backbone is of proven benefit, whether to use bevacizumab in the resectable or potentially resectable population is a clinical dilemma. Methods: Consecutive patients who underwent resection of liver metastases were identified from a prospective Australian mCRC registry that captures comprehensive data on patient and tumor characteristics (including resectability), treatment and outcome. The use of bevacizumab in this setting was examined and the impact on outcomes was explored. Results: From a total mCRC population of 1,700 patients, 543 patients with liver-only mCRC were identified, of which 217 patients (40%) underwent liver resection. Perioperative chemotherapy was administered to 185 patients (85.3%), with bevacizumab added to chemotherapy in 73 (39.5%) patients. There was a trend for bevacizumab treated patients to be younger (median age 60.4 vs 65.1 years, p = 0.07) and fitter (mean Charlson score 2.22 vs 2.64, p = 0.054). Patients that received bevacizumab with perioperative chemotherapy were considerably less likely to have disease regarded as resectable at diagnosis (39 of 73 (53.4%) vs 95 of 112 (84.8%), p =<.01). At 5 years, overall survival was similar for bevacizumab treated and non-treated patients (61.4% vs. 59.2%, HR 0.83, p=0.52). There were no deaths within 30 days of surgery in any patients. Conclusions: Despite limited evidence to support the use of bevacizumab in patients with resectable or potentially resectable liver-only mCRC, clinicians are not infrequently utilising this approach, particularly in younger and fitter patients and those not considered to have resectable disease at diagnosis. The addition of bevacizumab did not appear to impact survival outcomes. A multivariate analysis is underway to better define the impact of bevacizumab on survival outcomes.
Treatment patterns and outcomes in metastatic colorectal cancer (mCRC).
Authors: Cartwright Thomas H. , Wen Lonnie Kent , Harrell Robyn K. , Fox Patricia S. , Espirito Janet L. , Wang Ed
Published: February 2017

699

Background: Treatment (tx) selection for mCRC is multifactorial and affected by patient (pt) and disease factors, comorbidities, and previous tx. Few agents existed for therapy after second progression (i.e. third line (3L) at the time of this study. We aimed to capture mCRC tx patterns up to 3L and associated clinical and economic outcomes. Methods: A retrospective observational study of mCRC pts initiating 1L tx from 1/1/07 to 6/30/11 and 3L tx before 6/30/12. Data was extracted from The US Oncology Network (USON)/McKesson Specialty Health EHR and claims database. Pts on clinical trial or with another cancer diagnosis were excluded. Tx was organized into tx backbone categories and lines of therapy (LOTs), and adherence to NCCN guidelines and USON pathways assessed. The Kaplan-Meier method was used to estimate overall survival (OS). A multivariable generalized linear regression model was used to evaluate total costs during 3L tx as a function of 3L covariates by Medicare allowable. Clinical outcomes in 3L have been previously reported. Additional information on cost and other utilization is provided. Results: Of756 eligible 1L pts, 577 pts received 3L tx. At 1L, median age was 61 yrs (range 26-90+), male (55%), normal BMI (43%), ECOG performance status (PS) of 1 (65%), and Medicare (39%) insurance. The most utilized txs in 1L, 2L, and 3L were oxaliplatin-based (FOLFOX + bevacizumab, 46%), irinotecan-based (FOLFIRI + bevacizumab, 23%), and irinotecan + anti-EGFR (irinotecan + cetuximab, 24%) respectively. Adherence to NCCN and USON recommendations for 1L, 2L, and 3L was 88%/75%/55% and 84%/62%/38% respectively. OS in 3L was influenced by PS, BMI, and KRAS (p < 0.05), but was not different by tx backbone (p = 0.47). In the multivariable model of total cost per pt in 3L, there were no significant predictors. Conclusions: Knowledge of tx sequencing aids in understanding selection choices and outcomes in pts who are candidates for later lines of therapy of mCRC. High utilization of targeted therapies was observed in each line. Adherence to guidelines decreased with increasing lines of therapy. Utilization and costs by tx backbone in the 3L during this time frame varied. 3L OS did not differ according to tx backbone.
Efficacy and safety of FOLFIRI regimen in elderly versus nonelderly patients with advanced colorectal and gastric cancer.
Authors: Kim Jin Won , Kim Kyu-Pyo , Lee Ju Hyun , Hong Yong Sang , Kim Sun Young , Park Sook Ryun , Nam Byung-Ho , Lee Keun-Wook , Chung Ik-Joo , Park Young Suk , Kim Jee Hyun , Kim Tae Won
Published: February 2017

701

Background: Irinotecan-based chemotherapy is a standard backbone in patients (pts) with advanced colorectal (CRC) or gastric cancer (GC). However, there is still a paucity of information concerning the efficacy and safety of irinotecan-based regimen in elderly pts. Methods: Using pt cohort (N = 1,545) of the UGT1A1 genotype study (Kim KP, et al. J Clin Oncol 33, 2015 (suppl; abstr 3600)), we performed subgroup analysis comparing the efficacy and safety between elderly (age ≥ 70 years, median 73 years, N = 245) and non-elderly ( < 70 years, median 57 years, N = 1,300) pts with advanced CRC or GC who received first- or second-line FOLFIRI chemotherapy. Results: In both CRC (N = 934) and GC cohorts (N = 611), elderly pts received significantly lower dose of irinotecan (CRC: mean 74.8% vs. 80.9%, P < 0.001; GC: 72.4% vs. 76.2%, P = 0.018) and infusional 5-fluorouracil (CRC: 61.6% vs. 71.8%, P < 0.001; GC: 47.1% vs. 55.8%, P = 0.004). However, the response rate was similar between elderly and non-elderly pts in both CRC (28.7% vs. 32.9%, P = 0.347) and GC cohorts (22.9% vs. 18.3%; P = 0.369). The progression-free survival was also similar between the two age groups in both CRC (median 27.9 vs. 29.1 weeks, P = 0.202) and GC cohorts (20.1 vs. 17.0 weeks, P = 0.407). In addition, the overall survival was comparable between the two age groups in both CRC (81.9 vs. 91.8 weeks, P = 0.965) and GC cohorts (33.6 vs. 49.3 weeks, P = 0.085). In both cohorts, asthenia was significantly more frequent in elderly pts, while nausea and vomiting were significantly more frequent in non-elderly pts. In CRC cohort, grade 3-4 toxicities that were significantly more frequent in elderly pts were asthenia (1.3% vs. 0.2% per cycle, P < 0.001), mucositis (0.4% vs. 0.1%, P = 0.021), and anorexia (0.8% vs. 0.2%, P = 0.005) in CRC cohort. However, in GC cohort, grade 3-4 toxicities were not significantly different between the two age groups. Conclusions: Despite relatively lower dose intensity in elderly pts, efficacy of FOLFIRI regimen in this subset was comparable to that of non-elderly pts. FOLFIRI regimen was relatively well tolerated in elderly pts. Taken together, FOLFIRI is a considerable standard backbone in elderly pts with advanced CRC or GC.
Adjuvant pelvic radiotherapy in patients with stage IVA rectal adenocarcinoma.
Authors: Fossum Croix C. , Romak Lindsay B. , Funk Ryan K. , Harmsen William S. , Haddock Michael G. , Neben-Wittich Michelle A. , Martenson James A. , Larson David W. , Mathis Kellie L. , Smoot Rory L. , Hubbard Joleen Marie , Hallemeier Christopher Leigh
Published: February 2017

711

Background: For patients with stage IVA rectal cancer with liver metastases treated with curative-intent chemotherapy and surgery, the role of adjuvant pelvic radiotherapy (RT) is unclear. The purpose of this study was to evaluate the impact of pelvic RT on oncologic outcomes in this patient population. Methods: We retrospectively reviewed medical records of all patients with stage IVA rectal adenocarcinoma with liver metastases treated with curative-intent resection of the primary tumor and all liver metastases at our institution between 1991 and 2010. Patient and treatment characteristics were compared between patients who did or did not receive pelvic RT using chi-square and unpaired ttests. Survival and recurrence estimates were calculated from date of initial diagnosis using the Kaplan-Meier method. Local recurrence (LR) was defined as recurrence in the pelvis occurring at or before distant recurrence (DR). Cox regression was used to compare rates of freedom from LR (FFLR), freedom from DR (FFDR), and overall survival (OS) between patients who did or did not receive pelvic RT. Results: The analysis included 65 patients. Median patient age at diagnosis was 59 years (range, 27-87). Tumor stage was T2 (n = 4), T3 (n = 53), or T4 (n = 8). The median number of liver metastases was 2 (range, 1-14). Surgery was low anterior resection (n = 54) or abdominoperineal resection (n = 11). All patients received perioperative fluoropyrimidine based chemotherapy. Pelvic RT was administered to 35 patients (54%), either preoperatively (n = 22) or postoperatively (n = 13). Median RT dose was 50.4 Gy (range 25-58). Patient characteristics were similar for those who did or did not receive pelvic RT. Median follow-up was 3.7 years. The 3-year estimates of FFLR, FFDR and OS were 81% vs 58% (p =.056), 35% vs 29% (p =.75), and 66% vs 71% (p =.81) for RT vs no RT, respectively. Conclusions: In this analysis of patients with stage IVA rectal cancer with liver metastases undergoing curative intent therapy, pelvic RT (vs. no pelvic RT) was associated with a trend to lower rates of LR and similar rates of DR and OS.
Nomogram including pretherapeutic parameters for prediction of early response after neoadjuvant treatment in rectal cancer: Results from a prospective randomized study.
Authors: Zhang Jianwei , Cai Yue , Hu Huabin , Lan Ping , Wang Lei , Huang Meijin , Kang Liang , Wu Xiaojian , Ling Jiayu , Xiao Jian , Wang Jianping , Deng Yanhong
Published: February 2017

716

Background: To establish a clinical nomogram with pretherapeutic parameters for predicting pathologic complete response (pCR) and tumor downstaging after neoadjuvant treatment in patients with rectal cancer. Methods: From Jan 2011 to Feb 2015, complete data was available for 309 patients with rectal cancer who received concurrent chemoradiotherapy or chemotherapy alone enrolled in FOWARC study. All pre-treatment clinical parameters were collected to build a nomogram for pCR and tumor down-staging. The model was subjected to bootstrap internal validation. The predictive performance of the model was assessed with concordance index (c-index) and calibration. Results: Of the 309 patients, 55 (17.8%) had achieved pCR, 138 (44.7%) patients were classified as good down-staging with ypTNM stage 0-I. Basing on the multivariate logistic regression and clinical consideration, 5 factors were identified to be the independent predictors for pCR and good downstaging, respectively (Table 1). The predictive nomograms were developed (fig 1 and 2) to predict the probability of pCR and good down-staging with a C-index of 0.802 (95% CI: 0.736-0.867) and 0.73 (95% CI: 0.672-0.784). Calibration plots showed good performance on internal validation. Conclusions: The nomograms provide individual prediction of response to different preoperative treatment for patients with rectal cancer. This model may help physician in patient selection for optimized treatment. Further external validation is warranted. [Table: see text]
Short- and long-term outcomes of neoadjuvant-synchronus S-1+radiotherapy for locally advanced rectal cancer: Multicenter phase II study.
Authors: Hiratsuka Takahiro , Akagi Tomonori , Nakajima Kentaro , Empuku Shinichiro , Shibata Tomotaka , Ueda Yoshitake , Tojigamori Manabu , Shiroshita Hidefumi , Etoh Tsuyoshi , Ninomiya Shigeo , Hiroishi Kazuaki , Takeuchi Yu , Sasaki Atsushi , Tahara Koichiro , Fujii Kyuzo , Shiromizu Akio , Ishikawa Koichi , Matsumoto Toshifumi , Bando Toshio , Inomata Masafumi
Published: February 2017

720

Background: Fluorouracil-based chemoradiotherapy (CRT) is regarded as a standard perioperative treatment in locally advanced rectal cancer. We investigated the efficacy and safety of substituting fluorouracil with the oral prodrug S-1. Methods: A multi-institutional (17 specialized centers), interventional phase II trial, was conducted from April 2009 to August 2011. For inclusion, patients must fulfill the following requirements before neoadjuvant CRT: (i) histologically proven rectal carcinoma; (ii) tumor located in the rectum (upper, lower); (iii) cancer classified as T3-4, N0–3 and M0; Two cycles of neoadjuvant CRT with S-1 (100 mg/m2 on days 1-5, 8-12, 22-26, and 29-33) was administered, and irradiation (total 45Gy/25fr, 1.8Gy/day, on days 1-5, 8-12, 15-19, 22-26, and 29-33) was performed. Total mesorectal excision was performed during the 4th and 8th week after the end of the neoadjuvant CRT. The primary endpoint is rate of complete treatment of neoadjuvant CRT. Secondary endpoints are response rate of neoadjuvant CRT, short-term clinical outcomes, rate of curative resection, and pathological response (grade2/3). Results: This trial included 37 patients (clinical StageIIA: 8, IIIB: 19, IIIC: 10; tumor located in the upper rectum; 4, the lower rectum; 33). A complete treatment of neoadjuvant CRT was found in 86.5% of patients (95%CI;75.5-97.5%), and an adverse event (grade 3/4) occurred in 4 patients(11.1%). Response rate (PR/CR;RECIST 1.0) was 56.8% (95%CI; 40.8-72.7%), and pathologic response rate (grade2/3) was 48.6% (95%CI; 32.5-64.8%). The median operating time was 448.5 min (IQR 340.5-505.5), and median blood loss was 422.5 mL (IQR 182.5-1125). Grade 3-4 postoperative complications occurred in 6 (16.7%) patients. The most common grade 3 or 4 postoperative complication was anastomotic leakage (2 [5.6%]). The 3-year overall survival rate was 88.5%. The 3-year disease free survival rate was 70.9%. Median length of follow-up was 42 months. Conclusions: A neoadjuvant-synchronus S-1+Radiotherapy for locally advanced rectal cancer is feasible in terms of pathological response, adverse events, accompany with favorable long-term outcome. Clinical trial information: 03396.
Prognostic significance of regional lymph nodes status in stage IV colorectal cancer.
Authors: Ahmed Shahid , Leis Anne , Kanthan Selliah , Fields Anthony L.A. , Reeder Bruce , Zaidi Adnan , Haider Kamal , Abbas Tahir , Iqbal Nayyer , Pahwa Punam
Published: February 2017

721

Background: Lymph node involvement is one of the most important prognostic variables in early stage CRC and an indication for adjuvant therapy. However, the prognostic significance of regional nodal metastases and the ratio of metastatic to examined lymph nodes (LNR), in stage IV CRC remain unknown. The current study aims to determine prognostic importance of nodal status and LNR in patients with stage IV CRC who undergo primary tumor resection (PTR). Methods: Retrospective cohort study involving patients with synchronous metastatic CRC diagnosed in Saskatchewan, during 1992-2010 and underwent PTR. Cox Proportional multivariate analyses were performed to determine prognostic significance of nodal status and LNR. Results: 2,294 patients were diagnosed with synchronous metastatic CRC during the study period. Of those 1257 underwent PTR, 148 patients did not have information about nodal status and were excluded. Median age of 1109 eligible patients was 70 yrs (22-98) and M:F was 1.2:1. 26% patients had rectal cancer, 96% had T3/T4 tumor, and 82% had node positive disease. The median LNR was 0.36 (0-1.0). 54% received chemotherapy. Median overall survival of patients who had LNR of ≥ 0.36 and received chemotherapy was 29.7 months (95% CI: 26.6-32.9) compared with 15.6 months (13.6-17.6) with LNR of < 0.36 [p < 0.001]. On multivariate analyses, among prognostic variables use of any chemotherapy, HR: 2.36 (2.0-2.79); metastasectomy, HR: 1.95 (1.63-2.32); nodal status, HR 1.34 (1.14-1.59); LNR ≥0.36, HR: 1.59 (1.38-1.84); and T status, 1.23 (1.07-1.40) were correlated with survival. Test for interaction was positive for LNR and high grade cancer, HR: 1.17 (1.031-1.33). In a sub-cohort of patients who underwent metastasectomy both LNR using a cut-off of 0.36 and nodal status, independent of chemotherapy and other prognostic variables were correlated with survival, HR of 2.38 (95%: 1.64-3.47) for LNR ≥ 36 and 1.57 (95% CI: 1.05-2.34) for node positive disease. Conclusions: Our results suggest that regional nodal status and LNR are important prognostic factor independent of chemotherapy in stage IV CRC patients undergoing PTR. Future studies are required to elucidate the mechanism by which nodal status affect survival in stage IV CRC.
Capecitabine dosing using skeletal muscle index (SMI) compared to body surface area (BSA).
Authors: Sun Julia , Ilich Alastair , Kim Christina , Wong Grace , Ghosh Sunita , Danilak Melanie , Mulder Karen E. , Spratlin Jennifer L. , Chambers Carole , Sawyer Michael B.
Published: February 2017

722

Background: Capecitabine dose used to treat colorectal (CRC) and breast cancer (BC) is calculated using BSA. Capecitabine dose is 1250 mg/m2 in CRC and 1000 mg/m2 in BC. Using BSA to calculate dose does not consider body composition. We hypothesize that differences in capecitabine dose between CRC and BC patients (pts) is due to body composition differences between men and women, not cancer type. We hypothesize females starting treatment at 1250 mg/m2 have a higher capecitabine dose/SMI than males, and dose reductions for dose-limiting toxicity (DLT) would lead to male and female CRC pts receiving the same capecitabine dose/SMI. Methods: This is a retrospective study of early stage CRC pts treated with adjuvant capecitabine from 2008-2012. Collected demographic data included age, stage, gender, height, weight, and performance status. Capecitabine doses at cycles 1 and 3 were documented. SMI was calculated using pre-treatment CT scans. Results: 183 pts (101 males, 82 females) were identified. Females received a higher starting capecitabine dose compared to males based on SMI. Mean capecitabine/SMI dose was 5107.4 mg/cm2/m2 (SD 1113.8) for females compared to 4711.9 mg/cm2/m2 (SD 870.6) for males (p = 0.009). At cycle 3, females still had a higher dose of 3875.1 mg/cm2/m2 (SD 1663.5), although it was not statistically significant from their male counterparts at 3691.6 mg/cm2/m2 (SD 1629.5) (p = 0.4580). Conclusions: Females received higher capecitabine doses/SMI than males at the CRC 1250 mg/m2 dose. This is in keeping with our previous study that showed female CRC pts on adjuvant capecitabine experience more DLTs compared to males. After adjusting capecitabine doses for DLTs, male and female CRC pts received the same cape dose/SMI. This suggests SMI may be more useful than BSA when adjusting capecitabine doses.
A retrospective comparison between regorafenib and TAS-102 for refractory metastatic colorectal cancer.
Authors: Masuishi Toshiki , Taniguchi Hiroya , Hamauchi Satoshi , Komori Azusa , Kito Yosuke , Mitani Seiichiro , Hasegawa Hiroko , Narita Yukiya , Kadowaki Shigenori , Ura Takashi , Ando Masashi , Mori Keita , Tajika Masahiro , Yasui Hirofumi , Muro Kei , Yamazaki Kentaro
Published: February 2017

723

Background: Regorafenib (R) and TAS-102 (T) prolonged survival for patients (pts) with refractory metastatic colorectal cancer (mCRC) in phase 3 trials. However, little is known regarding optimal sequence of administration of R and T, because of lack of head-to-head trials. Methods: We retrospectively evaluated pts who had been treated with R or T in two institutions from May 2013 to March 2015. Inclusion criteria were ECOG PS 0–2, refractory or intolerant to fluoropyrimidines, oxaliplatin, irinotecan, angiogenesis inhibitors, and anti-EGFR antibodies (if KRAS wild type), and no previous treatment with R or T. Results: A total of 182 pts (R/T: 138/44) were eligible for the study. The baseline characteristics were similar for the two groups as follows (R/T): median age, 64/63.5; male, 61%/52%; and KRAS wild type, 52%/59%. However, the proportion of pts with ECOG PS 2 (8%/18%) and who had not received irinotecan (1%/14%) was lower in R than in T. Efficacies were as follows (R/T): response rate, 0.8%/0%; disease control rate, 34%/33%; median time to treatment failure, 1.8/1.9 months (m) (median duration of follow-up, 5.6/5.0 m); median progression-free survival (PFS), 2.1/2.0 m (HR 1.09, p= 0.62, adjusted HR 0.97, p= 0.89 [11 covariates such as age, PS, and KRAS status]); median survival time (MST), 5.9/5.8 m (HR 0.92, p= 0.70); and MST for 74 eligible pts (R/T: 30/44) after the approval of T in Japan, 6.4/5.8 m (HR 0.94, p= 0.84, median duration of follow-up 4.7/5.0 m). Subgroup analysis suggested that pts with higher age and poor PS had shorter PFS in R than in T. The frequency (R/T) of grade 3 or 4 hand–foot syndrome and increased ALT were higher in R than in T (21%/0% and 10%/0%). Conversely, the frequencies of grade 3 or 4 neutropenia, anemia, and febrile neutropenia were lower in R than in T (2%/34%, 8%/27%, and 0%/7%, respectively). The main reason for discontinuation was disease progression (R/T: 85%/82%). Subsequent chemotherapies were received in 53%/46% (R/T). Conclusions: Our retrospective analysis suggested that regorafenib and TAS-102 had similar efficacy in patients with refractory mCRC. Our study results indicate that different toxicity profiles should be considered when selecting a drug treatment.
Time to first-line chemotherapy and travel distance to the cancer center and their relationship to subsequent-line therapies in stage IV CRC.
Authors: Iqbal Mahjabeen Fatima , Suo Aleksi Emil , Papneja Neha , Iqbal Nayyer , Abbas Tahir , Haider Kamal , Zaidi Adnan , Ahmed Shahid
Published: February 2017

724

Background: Second and third line therapies in stage IV colorectal (CRC) have been associated with significant improvement in survival. However, not all patients receive all available therapies. Delay in starting treatment and travel burden can affect patient access and use of future therapy. Little is known about time to first line chemotherapy (TC) and travel distance to cancer center (TD) and their relationship to future therapies in stage IV CRC. The study aims to determine relationship between TC and TD with second and subsequent line of therapies. Methods: A patients cohort diagnosed with synchronous stage IV CRC during 2006-2010 in the province of Saskatchewan, Canada was studied. Patients with ECOG performance status of > 1 or who did not receive chemotherapy were excluded. The logistic regression analyses were performed to assess relationship between TC and TD and subsequent line therapies. Results: 569 patients were diagnosed with synchronous stage IV CRC. 326 patients received first line chemotherapy (mostly FOLFIRI ± bevacizumab). Of 326 patients 62 with ECOG performance status (PS) > 1 were excluded. The median age of 264 eligible patients was 62 yrs (IQR:53-72). 61% were male and 38% had ECOG PS of 0. Mean Charlson score was 9±1.3. 24% underwent metastasectomy. Median TC was 77 days (IQR: 53-107) and median TD was 64.4 km (IQR:4.8-166). 42.8% patients had to travel > 100 km for their treatment. Of 326 patients 144 (55%) received future therapies. On multivariate analysis absence of comorbid illness (as per Charlson comorbid index), odd ratio (OR) 1.45 (95% CI: 1.19-1.77), no metastasectomy, OR 1.89 (1.03-3.46) and TD < 100 km, OR 1.69 (1.003-2.84) were correlated with the utility of 2ndand subsequent line therapies. Conclusions: Our result revealed that although time to first line chemotherapy did not correlate with future systemic therapies, travel distance to Cancer Center > 100 km was associated with low rate of second or subsequent line therapies in statge IV CRC patients with good performance status.
Systemic therapy for advanced anorectal squamous cell carcinomas: A single institutional experience.
Authors: Boland Patrick McKay , Wang Katy , Kohen Aniqa
Published: February 2017

728

Background: Anorectal squamous cell carcinomas (SCCs) are rare in the United States with < 10,000 cases annually. Uncommonly, patients present with stage IV disease or recurrence after definitive therapy. Limited options exist for these patients. We queried Roswell Park Cancer Institute (RPCI) patient records to determine systemic treatments utilized and outcomes for these patients. Methods: Patients with anal or rectal SCC between 1/1/99 and 7/1/2014 were identified via the cancer registry. 65 patients were flagged for review. From manual review, 31 patients received treatment at RPCI and were deemed evaluable. Demographic data, histology, staging, treatment history, time receiving any specific therapy and response assessment were abstracted from the records. Results: Of the 31 patients, 45% were male, 55% female. Primary tumors were anorectal (84%) or rectal (16%) in origin. 5(16%) presented with rectal SCC. Sites of metastatic disease were most commonly identified as lymph nodes (48%), liver (35) or lung (16%). At the time of analysis 5 (16%) were alive, with 3 (10%) disease free. Median overall survival (OS) was 44.1 months (95% CI, 28.9 - 62.6). The most commonly utilized chemotherapy regimens were 5-fu/cisplatin (n = 22 patients) and taxol (n = 10). Mean time on therapy was 4 months for 5-fu/platinum doublets (n = 24), 4 months for taxanes/platinum combinations (n = 6), 3.4 months for anti-EGFR containing regimens (n = 7) and 2.43 months for taxane monotherapy (n = 10). The most common reasons for discontinuation of therapy were progressive disease (47%) or patient choice (15%). Conclusions: New therapies are desperately needed for advanced anorectal SCCs. At present, 5-FU/cisplatin is the best endorsed and most frequently utilized regimen. Consistent with other reports, platinum doublets and anti-EGFR targeted therapies appear to confer significant benefits, within the realm of 5-fu/cisplatin, with single agent taxanes appearing to have lesser activity. Small absolute patient numbers and lack of reliable response measurements preclude firm conclusions. Future clinical trials to evaluate systemic therapies in advanced anorectal SCCs, including anti-EGFR regimens, are warranted.
Perioperative outcomes for robotic total mesorectal excision after preoperative chemoradiation for rectal cancer.
Authors: Nassour Ibrahim , Borja Nicholas , El-Mokdad Ali , Hirsch Hannah , Meyer Jeffrey John , Polanco Patricio , Balch Glen C.
Published: February 2017

732

Background: Laparoscopic total mesorectal excision (TME) after preoperative chemoradiation therapy (P-CRT) for mid to low rectal cancer was shown to be safe and feasible by a recent randomized trial (COREAN trial). However, the safety and short-term efficacy for robotic assisted laparoscopic TME has not been demonstrated. This study is a review of the perioperative outcomes of robotic TME after P-CRT for mid to low rectal cancer at our institution. Methods: All patients that underwent robotic TME after P-CRT for rectal cancer were retrospectively reviewed in our prospectively maintained, IRB-approved surgical oncology database. All relevant demographic, clinical, operative, pathology and perioperative data were analyzed. These were compared to the COREAN trial results. Results: From 2010 to 2014, 42 patients underwent robotic TME for rectal cancer after P-CRT. Mean patient age was 60+/-13. Robotic low anterior resections (R-LAR) were performed in 69% and 31% had a robotic abdominoperineal resection (R-APR). A majority were obese patients as 74% had a BMI ≥ 25, and 50% had an ASA ≥ 3. Conversion to open rate was 9.5% (n = 4) but 3 of these were within the first 8 cases. Median estimated blood loss was 105 ml (50-400 ml). The 30-day major complication rate (Clavien III-IV) was 11.9% (n = 5) and 90-day rate was 14.2% (n = 6). One patient (2.4%) had an anastomotic leak. There were no mortalities within 90-days from operation. Median length of stay was 7 days (6-12 days). Pathological complete response was 19% while 24% had no response. The average number of lymph nodes harvested was 14.2+/-9.5. The circumferential resection margin was negative in 95.2% (n = 40) of patients. Conclusions: As compared to laparoscopic TME patients in the COREAN trial, the robotic patients in our series were more obese and had a higher ASA classification. Our conversion rate was slightly higher, but this was related to the learning curve. All other short-term outcomes were similar. It appears that robotic TME is safe and feasible after P-CRT even among a more obese and higher risk population than previously reported in large series.
Rectal adenocarcinoma: Surveillance and timing of surgical resection after neoadjuvant chemoradiotherapy in a retrospective cohort.
Authors: Pachón Olmos Vanessa , Reguera Puertas Pablo , Saavedra Serrano Cristina , Ferreiro Monteagudo Reyes , Longo Federico , Guillén Ponce Carmen , Gómez Rueda Ana , Rodríguez Garrote Mercedes , Vaz Salgado María Ángeles , Gion Cortés Maria , Salgado Alfonso Cortes , Muñoz del Toro Jacobo , Cortez Castedo Silvia Patricia , Hervás Morón Asunción , Sempere Ortega Cayetano , Die Trill Javier , García Pérez Juan Carlos , Moreno Montes Irene , Tobaruela de Blas Estela , Carrato Alfredo
Published: February 2017

737

Background: There is some evidence relating delay of surgery (DS) by more than 8 weeks after the end of chemoradiotherapy and achievement of complete pathological response (ypCR). However, the relationship with overall survival (OS) seems to be negative. Methods: Records of 171 patients diagnosed from January 2003 to December 2011 with rectal adenocarcinoma T3/T4 and/or positive node staged by ultrasound or MRI were collected retrospectively from the Pathology Department database. Results: Of the 171 patients, 62% were male, median age at diagnosis 69.3 years (31.3 years -85.3 years). All of them received 50.4 Gy with different concomitant regimens (capecitabine, continuous infusion of fluoracil or bolus of fluoracil-leucovorin). 72.5% of the cohort received adjuvant chemotherapy. 13% of patients achieved ypCR, independently of DS (13.7% in DS vs 11.8%, p 0.722). OS was significantly worse among DS patients (67.9 months vs 54.8 months, p 0.016). In addition, more sphincter preservations (SP) were not achieved (60.8% in DS vs 57.1%, p 0.881). Conclusions: In contrast with published literature, in our cohort DS failed to show higher rates of ypCR. Neither an improvement in OS or SP was observed with DS. It is recommended that clinical trials be designed in order to establish ideal surgical timing.
Blood serum albumin as prognostic factor in patients with colorectal carcinoma.
Authors: Onate-Ocana Luis F. , Gonzalez-Trejo Sagrario , Nunez Gloria , Herrera-Goepfert Roberto , Carrillo Jose F. , Ochoa-Carrillo Francisco J. , Aiello-Crocifoglio Vincenzo
Published: February 2017

740

Background: During the las decades, Colorectal carcinoma (CRC) has become the commonest gastrointestinal neoplasm in Mexico, being stages III and IV the most frequent, reaching thus,, diagnosed by colonoscopy and biopsyand a dismal prognosis. Basal blood serum albumin has been reported as significant prognostic factor in several diseases and in several cancers. Therefore, our aim is to define the role of the basal measurement of blood serum albumin at diagnosis as prognostic factor. Methods: Consecutive cases with CRC diagnosed by colonoscopy and biopsy and treated at a single cancer center in Mexico City from January 2010 to December 2014, were included in this cohort. Clinical history and laboratory data were registered, and patients were treated according to standard guidelines. Follow-up continued until September 2015; the Kaplan-Meier method and the Cox model were used to analyze the association of prognostic factors and overall survival (OS). Results: There were 567 patients with CRC: 258 women (45.5%) and 309 males (55.5%); mean age was 60.04 years (SD 15.6). Fifty-seven, 155, 113 and 242 were stages I, II, III and IV, respectively; 132 were located in right colon, 33 in transverse, 35 in left, 114 in sigmoid, 239 in rectum and 14 in anal canal. Neither gender, age, blood hemoglobin, lymphocyte count, albumin-lymphocyte interaction, nor Nutritional prognostic index were significantly associated with OS. Serum albumin was associated to OS, by bivariate and by multivariate analysis. This association remainded significant after adjustment for TNM stages, locations, and other clinically relevant factors. Conclusions: Serum albumin at diagnosis is an independent, significant, simple, cheap and widely available prognostic factor in patients with CRC in Mexico, adding significant prognostic information to TNM classification. Feasibly, it can be used to develop multivariate prognostic models with clinical impact.
Treatment strategy for obstructive colorectal cancer.
Authors: Iwagami Shiro , Miyanari Nobutomo , Kubota Tatsuo , Nakao Yousuke , Yamao Takanobu , Sugihara Hidetaka , Sawayama Hiroshi , Mizumoto Takao , Kitano Yuuki , Baba Hideo
Published: February 2017

741

Background: The number of patients with colorectal cancer has been increasing in all over the world. Approximately 10 percent of CRC is complicated by obstructive symptoms at the time of their diagnosis. Obstructive colorectal cancer (OCRC) could be a fatal because of perforation peritonitis or sepsis, and it is necessary to immediate treatment. The aim of this study was to explore the treatment strategies for patients with OCRC. Methods: Between April 2008 and December 2014, six hundred seventy two patients underwent surgery in out institute. The numbers of OCRC were 82 cases (12.2%). We evaluated the feasibility and effectiveness of our treatments for OCRC. Results: Treatment strategies were adopted according to the location of CRC. For patients with right-sided OCRC, we performed one-stage surgery. They underwent primary tumor resection and anastomosis at the same time. For left-sided OCRC, patients were treated by two-stage surgery. At first, they were managed by decompression of their colon with colostomy or transanal ileus tube, and then, underwent colectomy. The cases of right-side OCRC were 23 cases, and all of them underwent one-stage surgery. We could find no cases of anastomotic leakage in these cases. The cases of left-side OCRC were 59 cases, and 50 patients (86%) of them were treated two-stage surgery. Stage IV OCRC patients tended to undergo colostomy only. Conclusions: One-stage surgery was feasible for patients with right-sided OCRC. For left-sided OCRC cases, two-stage surgery was effective to prevent perioperative complications.
Outcome comparison between bridge to surgery stenting and emergency surgery in stage II, III obstructive left colon cancer: A multicenter retrospective study.
Authors: Yoo Han-mo , Kang Won-Kyung
Published: February 2017

747

Background: A SEMS (Self Expandable Metallic Stents) has been widely used for obstructive colorectal cancer as a bridge to surgery to avoid emergency surgery. However, it may increase the tumor spillage so that the long-term survival would be compromised. The aim of our study was to compare the short- and long-term outcome of surgery after stent insertion with those of emergency surgery alone for the left colon malignant obstruction patients. Methods: The medical records of patients who received curative resection due to obstructive primary left colon cancer and diagnosed to stage II or III from January 2004 to December 2010 in six hospitals affiliated to the Catholic Medical Center. Overall survival and disease free survival were compared between the SEMS (n = 158) and emergency surgery (n = 56) group. Short-term outcome was also compared. Factors affecting disease-free survival in the SEMS group were analyzed using the cox proportional hazards model. Results: Baseline characteristics were comparable between two groups by pathologic stage. Intra-operative complication (0.0% vs. 7.1%, p = 0.004), re-operation (1.3% vs. 7.1%, p = 0.042), post-operative hospital stay (11.2 ± 6.5 days vs. 14.6 ± 8.9 days, p = 0.010) and conversion rate (3.5% vs. 16.7%, p = 0.028) showed short-term advantages of the SEMS. 5-year DFS in stage II patients was 87.2% for the SMES group, 73.5% for the ES group (p = 0.117). Among stage III patients, 5-year DFS was 55.8% for the SEMS group and 72.0% for the ES group (p = 0.129). 5-year OS of the SEMS group was 90.2%, and of the ES group was 92.4% in stage II patients (p = 0.694). 5-year OS in the SEMS group was 82.8%, and the ES group 73.0% in stage III patients (p = 0.577). For the stage III SEMS patients, hospital of procedure (p = 0.041) and operation date (HR 0.400, 95% C.I 0.176-0.905, p = 0.028) were independent factors on disease free survival. Conclusions: If there’s an intervention team with sufficient experience for the SEMS and a sufficient preparation for emergency surgery, the SEMS is a good therapeutic option for malignant obstruction in left colon cancer.
Effect of first-line molecular targeted agents on the efficacy of second-line bevacizumab-containing regimen for metastatic colorectal cancer.
Authors: Hasegawa Hiroko , Taniguchi Hiroya , Mitani Seiichiro , Komori Azusa , Masuishi Toshiki , Narita Yukiya , Kadowaki Shigenori , Ura Takashi , Andoh Masashi , Muro Kei
Published: February 2017

748

Background: Bevacizumab (BV)-containing regimen is a standard second-line chemotherapy(CTX) for patients (pts) with metastatic colorectal cancer (mCRC) regardless of the prior use of BV in the first-line CTX. However, little is known about the efficacy of the second-line BV-containing regimen after first-line CTX with anti-EGFR agents. Methods: We retrospectively evaluated the efficacy of a BV-containing regimen as the second-line CTX for mCRC. The eligibility criteria for the pts included in the study were as follows: ECOG PS 0–2, KRAS wild-type tumors, and refractory to first-line CTX with fluoropyrimidine and oxaliplatin or irinotecan from March 2007 to March 2015. The Kaplan–Meier method with a log-rank test and Cox regression analysis were performed to evaluate the progression-free survival (PFS) of the pts. Results: A total of 123 pts were eligible. The pts’ characteristics were as follows: males/females 73/50, median age 59 years, PS 0-1/2 118/5, LDH levels < 400IU/l / ≥ 400IU/l 91/32, second-line CTX regimen FOLFIRI+BV/FOLFOX+BV 111/12. The patients were categorized into the following 3 cohorts according to the prior use of molecular targeted agents: anti EGFR agents (cohort E, 35 pts), BV (cohort B, 58 pts), no molecular targeted agents (cohort C, 30 pts). There was hardly any difference in the baseline characteristics of the 3 cohorts; however, LDH levels in cohort E were higher than those in the other cohorts. Treatment efficacies were as follows (cohort E/B/C): response rate, 30%/10%/20%, with a significant difference between cohort E and B (OR = 1.50, p = 0.035) and median PFS, 8.6/5.9/6.9 months, with a significant difference between cohort E and B (p = 0.025). Multivariate analyses for PFS were adjusted for baseline characteristics such as histology, PS, chemotherapy regimen, presence of peritoneal metastasis, LDH levels, and duration of PFS in the first-line CTX. The PFS of cohort E was better than that of cohort B (HR = 2.180, p = 0.0025) and was not much different from that of cohort C (HR = 1.682, p = 0.64)in multivariate analyses. Conclusions: The second-line BV-containing regimen is effective regardless of the prior use of anti-EGFR agents.
Impact of relative dose intensity and G-CSF use in the adjuvant treatment of resected colon cancer.
Authors: Breadner Daniel Adam , Whiston Frances , Stitt Larry , Welch Stephen
Published: February 2017

752

Background: The benefits of adjuvant chemotherapy in stage III colon cancer (CC) are well established. However, the consequences of dose delays and modifications are not well established. Relative dose intensity (RDI) and dose scheduling have been shown to have prognostic significance in a number of cancers. We examine the effect of RDI, dose intensity (DI) and dose delays on disease free survival (DFS) and overall survival (OS) in stage III CC. Furthermore, we investigate the role of G-CSF in CC and its role in preserving RDI, and its effect on outcomes. Methods: A retrospective review was conducted for patients with stage III CC seen at a Canadian academic cancer center between 2006 and 2011. Patients who received at least three cycles of FOLFOX or at least two cycles capecitabine were included in the analysis. The RDI and DI were calculated and examined for correlation with DFS and OS. The influence of G-CSF on RDI and DI was also investigated. Results: FOLFOX was used more commonly than capecitabine, 64% vs. 36%. Within the FOLFOX regimen median RDI for oxaliplatin was 76.3%, and 83.5% for 5-FU. Median capecitabine RDI was 73.8%. Median DI were similar at 75.4%, 86.5%, and 69.1%, respectively. 60% of patients receiving FOLFOX got over 80% of their intended dose, while only 29% of patients receiving capecitabine achieved this DI. 3-year DFS was higher when RDI or DI was > 80%, compared to ≤ 80%, for each chemotherapeutic, however the differences did not reach significance. 3-year OS trended towards being higher in patients with an RDI and DI > than 80%, however there were limited events in these groups. Over half of patients on FOLFOX experienced a dose delay, 56.9%, most of whom then received G-CSF, 64.9%. Patients who received G-CSF had a higher DI than those who did not, 74.9% and 87.4% versus 66.5% and 76.8%, for the oxaliplatin and 5-FU components, respectively. 3-year DFS and OS was higher in patients who received G-CSF versus those who did not, 78.3% and 97.5% vs. 69.8% and 91.5%, respectively. Conclusions: In patients with stage III colon cancer an RDI or DI is associated with improved 3-year DFS and OS, although the difference did not reach significance in our review. G-CSF as secondary prophylaxis improves RDI, DI, DFS and OS.