bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loco-regional outcomes of a population-based cohort of rectal neuroendocrine tumors.
Authors: Tsang Erica S , McConnell Yarrow Jean , Schaeffer David F. , Speers Caroline , Kennecke Hagen F. 
Published: February 2017

668 Background: Optimal management of rectal neuroendocrine tumors (NETs) is not well defined. We characterized the clinicopathologic features, loco-regional, and systemic management of a population-based cohort of rectal NETs. Methods: Patients diagnosed with rectal NETs from 1999-2011 were identified from British Columbia provincial databases. NETs were classified as G1 and G2 tumors with a Ki-67 ≤ 20% and/or mitotic count ≤ 20 per high power field. Results: Of 91 rectal NETs, median age was 58 (IQR 48-65) years and 35 (38%) were male. Median tumor size was 6 (IQR 4-8) mm. Median overall survival was 164.7 months, with 3 patients presenting with stage IV disease. Treatment included local excision (n = 79), surgical resection (n = 6), and pelvic radiation (n = 1; T3N1 tumor). Final margin status was positive in 17 (20%) cases. Local relapse occurred in 8 (9%) cases, and one relapse to bone 13 months after T3N1 tumor resection. Univariate analysis demonstrated an association between local relapse and T classification, Ki-67, mitotic count, grade, and perineural invasion (p< 0.01), but not N or M classification, or lymphovascular invasion. Local relapse was not associated with surgical management or margin status. Of 3 patients with metastatic disease, two received systemic management, with capecitabine and temozolomide. Conclusions: Rectal NETs generally presented with small, early tumors and were treated with local excision or surgical resection without pelvic radiation. [Table: see text]
ARID1A alterations in gastrointestinal cancers as therapeutic opportunities.
Authors: Basu Gargi D. , White Tracey , LoBello Janine R , Lau Kevin R , Syring Michael , Krishnan Subha , Gonzalez Laura , Royce Thomas , Kurdoglu Ahmet , Halbert Matthew J , Kiefer Jeff , Cherni Irene , Aldrich Jessica , Izatt Tyler , Russell Megan , Nasser Sara , Carpten John D. , Craig David W. , Demeure Michael J 
Published: February 2017

671 Background: The gene encoding the AT-rich interacting domain (ARID1A) is a tumor suppressor and a subunit of the Switch/Sucrose Non fermentable (SWI/SNF) chromatin remodeling complex that regulates gene expression. Additionally, ARID1A functions to maintain genomic integrity by interacting with ATR. Mutations in ARID1A have been observed in a number of cancers. Inactivation of ARID1A has been reported to lead to increased sensitivity to inhibitors of PARP and PI3K/AKT pathway. We evaluated ARID1A alterations in gastrointestinal (GI) cancers to identify new therapeutic options. Methods: Comprehensive genomic profiling was performed on 55 GI cancer samples with 28 metastatic and 27 primary samples. Targeted sequencing was performed on 562 cancer associated genes in paired tumor and blood DNA samples. Results: ARID1A alterations were noted in 20% (11/55) of GI cancers. Alterations included frameshift and nonsense mutations, INDELs and structural breakpoints which are predicted to cause loss of ARID1A function. Tumor tissues harboring ARID1A alterations included 2/8 gastro-esophageal cancers, 2/2 duodenal cancers, 3/29 colorectal (CRC) cancers, 2/2 small bowel cancers, and 2/7 bile duct cancers. Mutations in the C-terminal half of ARID1A, known to interact with ATR and mediate its recruitment to double strand breakpoints was present in 2/11 samples. No pathogenic changes in the DNA repair genes (BRCA1/2, CHEK1/2, ATM, ATR or PALB2) or MMR genes were present in the tumors harboring ARID1A alterations. Interestingly, ARID1A mutations frequently coexisted with alterations leading to activation of the PI3K pathway. We found 45% (5/11) samples with mutated ARID1A had pathogenic alterations in PIK3CA, AKT, NF1, STK11, TSC1 and TSC2 genes which may increase sensitivity to PI3K pathway inhibitors. Conclusions: Targeted sequencing demonstrated that ARID1A is a frequent event in GI cancer. Our results suggest there may be a correlation between samples with ARID1A alteration and PI3K/AKT pathway activation which may lead to therapeutic opportunities with PI3K pathway inhibitors. The presence of ARID1A mutations especially those in the C-terminal half may predict clinical utility of PARP inhibitors in GI cancer.
Optimal timing for curative surgery after preoperative chemoradiotherapy in locally advanced rectal cancer.
Authors: Kwak Yoo-Kang 
Published: February 2017

677 Background: This study is a multicenter retrospective analysis conducted by the Korean Radiation Oncology Group (KROG) to identify the optimal operation timing after preoperative chemoradiotherapy (CRT) in rectal cancer. Methods: The study included data of 1786 patients who were diagnosed with locally advanced rectal cancer (cT3-4N0-2M0) and received preoperative CRT followed by curative surgery from 2003 to 2014, at 8 institutions in Korea. Total radiation dose was 50.4 Gy in 28 fractions, delivered in 1.8 Gy per fraction. All patients received total mesorectal resection. Interval time between preoperative CRT and surgery ranged from 1 week to 136 weeks, and median interval time was 7 weeks. Downstaging rate was assessed by comparing clinical pre-CRT and pathological post-CRT stages and downstaging was defined as ypStage 0-I (ypT0-2N0M0). Pathologically complete response (ypCR) was defined as the complete absence of viable tumor (ypT0N0M0). Primary end point of this study was to evaluate the period of highest downstaging and ypCR rates to determine the optimal timing for surgery after CRT. Results: Analyses on downstaging and ypCR rates were done with all patients. Downstaging rates peaked between 6 and 7 weeks and declined afterwards. ypCR rates increased from 5 to 6 weeks and decreased after 9 to 10 weeks. The patients were divided into two arms according to the median interval time between preoperative CRT and surgery. Downstaging rates were similar between the two arms showing 36.9% in the early arm (≤ 7 weeks) and 37.0% in the delayed arm ( > 7 weeks). However, ypCR rates were significantly higher in the delayed arm, compared to the early arm (12.3% vs. 8.6%, p = 0.011). Complete tumor regression was superior in the delayed arm, as compared to the early arm (13.2% vs. 9.1%, p = 0.004). The delayed arm had higher sphincter preservation rates than the early arm with a marginal significance (92.4% vs. 89.9%, p = 0.078). There was no statistically significant difference regarding overall survival and disease-free survival. Conclusions: The optimal timing for surgery for advanced rectal cancer is after 7 weeks and before 10 weeks following preoperative CRT.
Clinical effectiveness of adjuvant chemotherapy (AC) with or without oxaliplatin following neoadjuvant chemoradiotherapy (nCRT) in stage II rectal cancer (RC).
Authors: Loree Jonathan M. , Kennecke Hagen F. , Powell Erin Diana , Goodwin Rachel Anne , Tang Patricia A. , Heng Daniel Yick Chin , Price Hiller Julie A. , Monzon Jose Gerard , Vickers Michael M. , Cheung Winson Y. 
Published: February 2017

686 Background: Use of AC in RC following nCRT is controversial because of concerns regarding its potentially small magnitude of benefit. We aimed to 1) examine real-world patterns of AC use in stage II RC and assess its impact on outcomes and 2) determine whether the addition of oxaliplatin to fluoropyrimidines modifies effectiveness. Methods: Using a cohort of yp stage II RC patients from 5 Canadian centers that underwent curative surgery, we assessed the relationship between AC +/- oxaliplatin and overall (OS) and disease free survival (DFS). Cox models adjusting for age, gender, ECOG, and high risk features (T4 lesion, poor differentiation, inadequate lymph node sampling, lymphovascular/perineural invasion, and obstruction/perforation) were constructed. Results: Among 485 pts, 74% received AC of whom 19% received oxaliplatin-based treatment. Median follow up was 4.5 yrs. Pts in the AC group were younger (median age 61 vs 64; P= 0.003) and had higher rates of TME (82% vs 79%; P= 0.049), but they had similar demographics, ECOG, high risk features, preoperative CEA, margin status and nCRT regimen when compared to pts in the non-AC group (all P> 0.05). Multivariate analyses demonstrated that receipt of any AC (OS HR 0.93 95% CI 0.58-1.50 P =0.77; DFS HR 0.91 95% CI 0.58-1.43 P =0.69), fluoropyrimidine AC (OS HR 0.82 95% CI 0.49-1.36 P =0.44; DFS HR 0.83 95% CI 0.51-1.34 P =0.44), or oxaliplatin-based AC (OS HR 1.37 95% CI 0.74-2.55 P =0.32; DFS HR 1.17 95% CI 0.66-2.05 P =0.59) did not improve outcomes versus no AC. In subgroup analyses that stratified pts by high risk features, presence of 1, 2, or 3 high risk factors, preoperative CEA and margin status, AC did not result in better OS or DFS in any subgroup. A further exploratory analysis that focused only on those receiving AC within 12 weeks of surgery did not reveal any consistent correlations between AC and survival. Conclusions: Use of fluoropyrimidine or oxaliplatin-based AC in this multi-institutional cohort of yp stage II RC pts after nCRT did not improve outcomes compared to observation. Conventional high risk features used to risk stratify stage II colon cancer for AC decision making have limited utility in RC after nCRT.
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.