bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating parent of origin effects (POE) and anticipation in Irish Lynch syndrome kindreds.
Authors: Farrell Michael P. , Hughes David J. , Schmid Jasmin , Boonstra Philip S. , Mukherjee Bhramar , Walshe Margaret B. , Mac Mathuna Padraic M. , Gallagher David J. 
Published: February 2017

431 Background: Genetic diseases associated with dynamic mutations often display parent-of-origin effects (POEs) in which the risk of disease depends on the sex of the parent from whom the disease allele was inherited. Genetic anticipation describes the progressively earlier onset and increased severity of disease in successive generations of a family. Previous studies have provided limited evidence for and against both POE effect and anticipation in Lynch syndrome. We sought evidence for a specific POE effect and anticipation in Irish Lynch syndrome families. Methods: Affected parent-child pairs (APCPs) (N = 53) were evaluated from kindreds (N = 20) from two hospital-based registries of MMR mutation carriers. POE were investigated by studying the ages at diagnosis in the offspring of affected parent-child pairs. Anticipation was assessed using the bivariate Huang and Vieland model. Results: Paired t-test revealed anticipation with children developing cancer mean 11.8 years earlier than parents, and 12.7 years using the Veiland and Huang bivariate model (p < 0.001). Conclusions: These data demonstrate a similar age at diagnosis among all offspring of affected mothers that was indistinguishable from affected fathers. Affected sons of affected mothers were diagnosed with cancer almost 3 years younger than female offspring; however, this finding failed to reach statistical significance. Genetic anticipation was present in this cohort of LS families, emphasizing the importance of early-onset screening. An additional 60 LS kindreds are under review and updated data will be presented at the meeting. [Table: see text]
Association of time to adjuvant chemotherapy (TTAC) and overall survival among patients with rectal cancer treated with preoperative radiation.
Authors: Gresham Gillian , Speers Caroline , Woods Ryan , Cheung Winson Y. , Schaff Kimberly , Fung Mayo , Kennecke Hagen F. 
Published: February 2017

461 Background: Studies suggest that delayed adjuvant chemotherapy (AC) beyond 8 weeks is associated with inferior survival in early-stage colon cancer (CA). The optimal TTAC in rectal CA remains unclear. The objective of this study was to determine the prognostic effect of TTAC in stage II and III rectal CA treated with standard preoperative (op) chemoradiation. Methods: Patients with stage II/III rectal CA treated with pre-op chemoradiation, received post-op AC, and referred to the British Columbia Cancer Agency between 1999 and 2008 were included. Univariate and multivariate analyses were conducted using Kaplan Meier and Cox regression methods to evaluate the association between TTAC and outcomes. X-tiles cut-point analysis was performed to determine the optimal TTAC. Results: A total of 327 eligible patients were identified: median age 61 (range 22-85), 70% male, and 75% stage III. In terms post-op AC, 51% received 5-fluorouracil (5-FU), 32% received capecitabine, 12% received 5-FU and oxaliplatin, and 5% received other chemotherapy. Median TTAC was 7.0 weeks (wks) (range 1.6-33.3 wks). Cut-point analysis revealed the optimal TTAC to be 5.6 wks (HR: 0.42, 95%CI 0.22-0.82, p=0.0087). Initiation of AC within optimal TTAC (5.6 wks) and 6 wks from date of surgery (sx) was associated with a significant survival benefit while no significant effect was seen at 8 wks. TTAC of ≤ 6 wkswas found to be a significant prognostic factor in multivariate analysis (p=0.047) adjusted for ECOG, age, sex, stage, margin status, and grade. In stratified analysis by stage, patients with stage III disease benefited from AC (p=0.018) while those with stage II did not (p=0.71). Conclusions: In this study, the optimal TTAC was 6 weeks or less. Initiation of AC within this time frame was associated with improved OS. This is less than the optimal timeframe indicated in the literature for colon CA. [Table: see text]
Predictors of gastrointestinal toxicity during pelvic radiotherapy.
Authors: Yang T. Jonathan , Oh Jung Hun , Son Christina , Apte Aditya , Deasy Joseph O. , Wu Abraham Jing-Ching , Goodman Karyn A. 
Published: February 2017

472 Background: To identify clinical and dosimetric factors associated with acute gastrointestinal (GI) toxicities due to pelvic radiotherapy (PRT) in patients with rectal cancer. Methods: We analyzed 177 consecutive rectal cancer patients treated between 2007-2010. Clinical information including age, gender, stage, chemotherapy, and weekly proctitis and diarrhea grade (CTCAE 3.0) during PRT were obtained. The bowel, rectum, and anal canal were contoured on CT treatment planning images. Doses to GI structures were calculated using the original treatment plan, and dose-volume parameters were extracted for modeling using CERR software. Logistic regression models were used to test the association between GI toxicity grade and predictors. Results: The mean age was 59; 76 (43%) patients were women; 166 (94%) received concurrent 5-FU based chemotherapy. Over half (56%) were treated with intensity modulated radiotherapy (IMRT), 44% were treated with 3D conformal RT (3DCRT). Grade 2+ proctitis and diarrhea were seen in 57 (32%) and 44 (25%) patients, respectively. On univariate analysis, age inversely predicts for Grade 2+ proctitis (Rs=-0.22, p=0.009). 3DCRT (Rs=0.27, p=0.001) and female gender (Rs=0.28, p=0.0008) predict for Grade 2+ diarrhea. On multivariate analysis, the normal tissue complication model including volume of anal canal receiving >15Gy, anal canal minimal dose, and age was most predictive of Grade 2+ proctitis (AUC=0.67, Rs=0.25, p<0.001). The model including bowel volume receiving 45Gy, female gender, and use of 3DCRT was highly predictive of Grade 2+ diarrhea (AUC=0.76, Rs=0.35, p<0.001). Patients treated with IMRT had significantly less bowel volume receiving ≥ 45Gy compared to 3DCRT (V45Gy=10.9% vs. 21.7%, p<0.0001). Conclusions: In this analysis of a large cohort of patients receiving PRT for rectal cancer, we identified clinical and dosimetric predictors of acute GI toxicity. Younger patients and women have higher rates of acute Grade 2+ proctitis and diarrhea, respectively. IMRT resulted in a 50% relative reduction in bowel volume receiving 45Gy and a lower risk for clinically significant diarrhea. Dose-volume constraints using these parameters should be considered, particularly in higher risk patients.
Patterns of care of locoregional radiation therapy in patients with stage IV rectal cancer: A SEER analysis.
Authors: Logan Jennifer K. , DiPetrillo Thomas A. , Leonard Kara Lynne 
Published: February 2017

477 Background: Per the 2012 NCCN guidelines, pelvic radiation therapy (RT) is one of the preferred treatment regimens for patients with metastatic rectal cancer (MRC). This study aims to analyze patterns of care and outcomes data for the use of neoadjuvant/adjuvant pelvic RT in patients with MRC using the SEER database. Methods: Patients with stage IV rectal or rectosigmoid cancer were identified in the SEER database (1973-2009). Patients were stratified according to their primary site of disease (rectum vs. rectosigmoid), T-, and N-stage. Treatment regimens (+/- surgical resection, +/-RT, or a combination of both) were recorded. Fischer's exact test was used to compare RT rates based on stratified factors. 2-yr survival rates were compared among treatment groups. Results: A total of 6,873 patients with stage IV rectal CA and 3,417 patients with rectosigmoid CA were identified. In total, 20.5% of rectal CA patients received surgery alone while 38.7% received RT alone or RT + surgery. Within the rectosigmoid group, 51.4% of patients received surgery alone and 15.1% of patients received either RT alone or RT + surgery. The use of RT differed significantly between those with Tis-2 and T3-4 disease (p < 0.001) and between those with N0 vs. N1-2 disease (p < 0.001). 2-yr and 5-yr survival differed significantly between treatment groups with the highest survival rates among those receiving surgery and RT. Detailed data is provided in the table below. Conclusions: The primary treatments for patients with MRC include surgery +/- RT. RT is used more commonly in patient with primary rectal (as opposed to rectosigmoid) tumors, N0, or Tis-T2 disease. Treatment with combination surgery and RT is associated with prolonged survival. [Table: see text]
Effectiveness of bevacizumab (BV) beyond disease progression in metastatic colorectal cancer (mCRC): Analyses by sex in the ARIES observational cohort study (OCS).
Authors: Cohn Allen Lee , Hurwitz Herbert , Bekaii-Saab Tanios S. , Bendell Johanna C. , Kozloff Mark , Tezcan Haluk , Flick Elizabeth Dawn , Mun Yong , Fish Susan , Dalal Darshan , Grothey Axel 
Published: February 2017

514 Background: Randomized trials and OCSs have demonstrated that BV treatment in 1st-line (1L), in 2L, and across multiple lines is associated with longer survival in patients (pts) with mCRC. This analysis was aimed at comparing the effectiveness of BV after 1st disease progression (PD) between male and female mCRC pts who received 1L BV-containing therapy in a real-world setting. Methods: ARIES is a large, prospective OCS that enrolled pts who received BV and chemotherapy (CT) for 1L mCRC. Post-PD effectiveness was assessed for men and women characterizing BV use by cumulative and dichotomous approaches. The primary analysis treated BV exposure as cumulative BV doses after 1st PD and post-progression overall survival (ppOS) as the time from 1st PD to death. A time-dependent Cox regression model was fitted to assess the effect of cumulative BV exposure on ppOS, while controlling for potential confounders. A dichotomous secondary analysis characterized BV exposure as receipt of CT + BV (BBP) or CT alone (No BBP) within 2 months after PD and ppOS as time from 1st PD + 2 months to death. Results: Among the 1,550 1L mCRC pts enrolled, 1,199 (532 women) had PD. In the primary analysis, hazard ratios (HRs) for ppOS decreased, on average, by 1.2% with each additional BV dose. When stratified by sex, the average risk reduction per BV dose over 15 doses was 1.8% in women and 0.7% in men. In the secondary analysis that included 331 women (BBP, 180; No BBP, 151) and 417 men (BBP, 245, No BBP, 172) who received BV ± CT within 2 months post-PD, the HRs for ppOS with BBP treatment were 0.46 (95% CI, 0.35–0.59) in women and 0.52 (95% CI, 0.41–0.67) in men. Statistical interaction tests for differences in the effectiveness of BV between men and women were negative for primary and secondary analyses (P of 0.58 and 0.77). Protocol-specified adverse events occurred in 17.8% of women and 10.2% of men in the BBP population; this difference was largely related to rates of hypertension (8.3% vs 2.4%, respectively). Conclusions: In ARIES, the effectiveness of BV after first PD was not statistically different between women and men with mCRC. Clinical trial information: NCT00388206.
The outcome of preoperative chemotherapy followed by surgery and upfront surgery for liver metastases from colorectal cancer.
Authors: Kim Jung Sun , Kim Sunyoung , Cho Hye Jeong , Shim Eun Kyung , Oh Jae Hwan , Kim Dae Yong , Han Sung-Sik , Kim Seoung Hoon , Park Sang Jae , Baek Ji Yeon 
Published: February 2017

516 Background: Hepatic metastasectomy is the only curative option for patients (pts) with colorectal liver metastases (CRLM) but the optimal sequence of surgery and chemotherapy has not been established. We evaluated disease-free survival (DFS) in pts who were treated with difference sequences for resectable CRLM. Methods: Pts who had radiologically diagnosed with CRLM and underwent preoperative chemotherapy (preopCT) followed by surgery or upfront hepatic resection from Jan 2008 to Dec 2010, in National Cancer Center, Korea, were identified and their medical records were reviewed. Pts with number of metastatic nodules (mets) less than 6, and who were untreated for metastastic setting were analyzed. Those with tumor invasion of major intrahepatic vessels, extrahepatic metastases, or combined other advanced cancer were excluded. Results: Of 208 pts who underwent hepatic metastasectomy for suspicious CRLM, 123 pts who fulfilled the above criteria were analyzed. 34 (28%) pts received preopCT followed by surgery and 89 (72%) pts underwent upfront surgery. Postoperative chemotherapy was administered for 34 (100%) of preopCT group and 73 (82%) of upfront surgery group. Number of mets, baseline tumor marker levels, and R0 resection rate were similar between the two groups. But, early relapse was more in upfront surgery group. DFS at 3 year was 14% (95% CI 29%-34%) in preopCT group and 48% (95% CI 36%-59%) in upfront surgery group. In multivariate analysis, age > 65, Charlson comorbidity index > 0, mets≥3, and R1/R2 resection were significantly associated with increased risk for DFS events, while PreopCT was marginally associated with adverse outcome (Table). Conclusions: Upfront surgery, rather than preoperative chemotherapy followed by surgery, might be a favorable treatment option for resectable CRLM in terms of DFS. [Table: see text]
Treatment patterns and costs in second-line (2L) metastatic colorectal cancer (mCRC).
Authors: Teitelbaum April H. , Evans Dana , Yu Elaine , Morlock Robert , Byfield Stacey DaCosta 
Published: February 2017

544 Background: Administrative claims databases are an important data source to examine treatment (tx) patterns, costs and outcomes, but are subject to limitations. This study included a chart review to assess a claims-based algorithm for identifying 2L mCRC patients (pts). Tx patterns and costs were compared between mCRC pts treated with bevacizumab (BEV) or cetuximab (CET). Methods: 2LmCRC pts were identified from a US commercial insurance claims database (1/2008-6/2011). Initial identification required pts to have ≥2 claims ≥30 d apart for colon or rectal cancer and metastatic (met) disease. Continuous enrollment for ≥6 mo before and after the date of 1st met claim, ≥2 lines of therapy (LOT), and 2L tx with BEV or anti-EGFR was required. 2L was defined as addition of any new agent ≥28 d after start of 1st LOT. Charts from 92 pts were abstracted and used to refine and corroborate the algorithm. Generalized Linear Models (GLM) were used to assess differences in healthcare costs between patients on BEV or CET during 2L. Results: The match rate of claims identified mCRC pts treated with multiple lines of therapy confirmed by chart abstraction ranged from 85% to 97%. Applying the final algorithm to the overall claims data resulted in the identification of 569 pts: 450 pts receiving BEV and 119 pts receiving CET. A total of 38 panitumumab patients were excluded from analysis due to small sample size. Pt characteristics were similar; mean age was 61 years and 58% were males. In 2L, BEV was commonly used with 5FU or capecitabine-based regimens (81%) and CET with irinotecan-based regimens (73%). BEV pts had significantly lower all-cause healthcare costs (adjusted difference: –$12,239, p=0.02), and medical costs (–$13,672, p=0.01) during 2L. While on second-line therapy, BEV pts also had lower average monthly all-cause and medical costs than CET pts. Sensitivity analysis using variations of the case finding algorithm yield similar results. Conclusions: The use of BEV during second line treatment of mCRC was found to be associated with significantly lower healthcare costs relative to the use of CET from a large US healthcare claims database.
Effect of coinfusion of dexamethasone to oxaliplatin on hypersensitivity reactions induced by oxaliplatin in patients with colorectal cancer treated with XELOX.
Authors: Aisu Naoya , Yoshida Yoichiro , Miyake Toru , Tanimura Syu , Hoshino Seiichiro , Yamashita Yuichi 
Published: February 2017

560 Background: Oxaliplatin is a third-generation platinum compound and a key agent for the management of colorectal cancer. Patients treated with oxaliplatin are at risk for hypersensitivity reactions. The incidence of severe anaphylactic reaction of oxaliplatin is estimated to be 0.5%, whereas the incidence of other hypersensitivity reactions in clinical practice is estimated to be 12% to 20%. We have reported that there is possibility that hypersensitivity reactions to oxaliplatin could have been prevented by co-infusion of dexamethasone (DEX) (Yoshida et al.2012 ASCO-GI, Yoshida et al, Br J Med Med Res 2012) but just in a small cohort. This study was undertaken to evaluate the effectiveness of co-infusion of DEX to oxaliplatin for controlling hypersensitivity reactions caused by the administration of oxaliplatin. Methods: A retrospective study of patients with advanced colorectal cancer who received XELOX was performed. The study included 101 patients who received XELOX or XELOX +bevacizumab therapy for advanced or recurrent colorectal cancer. In all the patients, oxaliplatin (130mg/m²) was administered in combination with DEX (6.6mg) via the peripheral vein. Results: A total of 101 patients were studied. Hypersensitivity reactions developed in 2 patients (1.98%).Respiratory symptoms, ocular symptoms and anaphylaxis were not observed in 101 patients. Two patients experienced cutaneous reaction (erythema). Grade 3 or higher hemotoxicity was noted in 13.9% of the patients, and grade 3 or higher nonhematological toxicity was noted in 17.8% of the patients. The response rate was 55.4%. Conclusions: Co-infusion of dexamethasone to oxaliplatin reduced oxaliplatin-related hypersensitivity reactions. This effective approach should be considered for all patients who receive XELOX, allowing treatment to be completed as planned. We have already started a new phase II trial to confirm the effects of DEX to prevent the hypersensitivity.
A retrospective cohort study to determine the prognostic factors in metastatic colorectal cancer (mCRC) patients (pts) undergoing lung metastatectomy.
Authors: Socola Francisco , Nguyen Dao M. , Ochoa Roberto Enrique , Rocha Lima Caio Max S. , Hosein Peter Joel 
Published: February 2017

565 Background: Resection of liver metastases is now accepted as a potentially curative strategy in some pts with mCRC. Resection of lung metastases (LMs) may also be beneficial but this is not well established. We hypothesized that resection of LMs may lead to prolonged survival in highly selected pts with mCRC. Methods: In this IRB-approved retrospective cohort study, cases were defined as mCRC pts with LMs as their only site of disease who underwent metastatectomy. Controls consisted of mCRC pts who had LMs but did not undergo resection. Charts were reviewed for clinical characteristics; survival data was obtained from the institutional tumor registry. The primary endpoint was overall survival (OS) in the cases versus controls. The secondary endpoint was to determine prognostic factors associated with better survival. Results: We included 26 consecutive cases of mCRC undergoing resection of LMs and randomly selected 26 controls. All pts in the both groups were treated with contemporary chemotherapy, as well as bevacizumab and anti-EGFR monoclonals when appropriate. The median OS from the time of diagnosis with LMs was 29.8 months (95% CI 22.9-36.6) in the control group versus 56.6 months (95% CI 47.3-65.8) for the cases who underwent resection (log rank p=0.04). A number of baseline factors were significantly different between the cases and controls. The control group contained more pts with poorly differentiated tumors (p=0.016); had more pts with synchronous versus metachronous presentation of LM's (p=0.001); had more pts with multiple vs solitary LM's (p<0.001); and had more pts with bilateral vs unilateral LMs (p<0.001). The interval from initial diagnosis to the onset of LMs was significantly longer in the resection group vs controls (22.9 vs 2.9 months, p<0.001). Conclusions: In this retrospective study, pts with mCRC to the lung who were referred for resection were more likely to have well differentiated, solitary, unilateral tumors, with a long interval between the original diagnosis and the onset of LMs. Pts selected using these criteria may have a significant survival benefit from surgical resection of their LMs.
A novel preoperative protocol for locally advanced rectal cancer: Hyperfractionated short-course radiotherapy combined with chemotherapy.
Authors: Doi Hiroshi , Beppu Naohito , Takada Yasuhiro , Niwa Yasue , Fujiwara Masayuki , Kimura Fumihiko , Yanagi Hidenori , Yamanaka Naoki , Kamikonya Norihiko , Hirota Shozo 
Published: February 2017

577 Background: Neoadjuvant chemoradiotherapy (NACRT) has become a widely accepted strategy for rectal cancer (RC). The purpose of this study is to examine the safety and efficacy of a novel protocol of neoadjuvant hyperfractionated short-course radiotherapy (NAHSRT) combined with chemotherapy for locally advanced RC. Methods: 82 patients (pts) with RC were treated with NACRT followed by radical surgery between March 2008 and May 2012. 50 pts with RC of cT3N1M0 were analyzed in the present study. NAHSRT was performed with a dose of 2.5 Gy twice daily, with an interval of at least 6 hours between fractions, up to a total dose of 25 Gy (25 Gy in 10 fractions for 5 days) with chemotherapy. Radical surgery was performed within 3 week following the end of the NAHSRT. Results: 50 pts included 37 men and 13 women. The median age was 65.0 (range: 39-85) years. The median follow-up term was 12.0 (2-36) months. S-1, oxaliplatin with capecitabine, and fluorouracil, leucovorin plus irinotecan (FOLFIRI) was administered with NAHSRT in 48 pts, 1 pt, and 1 pt, respectively. 48 pts (96%) had no apparent adverse events before surgery. 49 pts (98%) completed NACRT except for 1 pt stopped chemotherapy (S-1) because of grade 3 gastrointestinal toxicity (CTCAE v.3). In addition, no pts showed grade 4 toxicities. Postoperative complications were found in 30 pts (60.0%). 33 pts (66.0%) received adjuvant chemotherapy. S-1, capecitabine, oxaliplatin with capecitabine, uracil/tegafur (UFT) and oral leucovorin, and oxaliplatin combined with S-1 (SOX) was delivered after surgery in 20 pts, 4 pts, 4 pts, 4 pts, and 1 pt, respectively. No pts. developed local failure, although distant failures were found in 3 pts. The median disease free survival and overall survival was 11.6 (2-36) months and 12.0 (2-36) months, respectively. In addition, disease-specific survival rate was 100.0%. Conclusions: We presented a novel protocol of NAHSRT for locally advanced RC and the short-term outcome. NAHSRT was well tolerated and produced excellent short-term outcomes in pts with locally advanced RC.
Expression of mRNA as a prognostic factor of colon-rectal cancer.
Authors: Watanabe Takafumi , Tamura Kazuhiko , Enomoto Masanobu , Saitho Hitoshi , Ohsaka Yoshiaki , Takagi Yuu , Tsuchida Akihiko 
Published: February 2017

585 Background: Several cancer-associated genes are known as prognostic factors of colon-rectal cancer. We measured and compared mRNA expression levels for each gene in colon-rectal cancer tissues obtained from biopsied and excised specimens. Methods: 53 cases of colon-rectal cancer surgery were examined. By the DNP method, mRNA expression levels of cancer-associated genes were measured. Measurements and examinations were performed for 10 genes: TS, DPD, TP, FPGS, GGH, DHFR, ERCC1, Topo-I, EGFR and VEGF. Results: Among 53 patients who underwent operations for colon-rectal cancer, a comparison was conducted between 43 recurrence-free patients and 10 metastatic recurrent patients. Conclusions: The results thereof showed a tendency in metastatic recurrent cases toward decreased activity of Topo-I. Topo-I’s decrease in activity is said to be related to CPT-11 tolerance, and its low degree of activity in metastatic recurrent cases is predicted to be a factor in poor prognoses. At the same time, ERCC1 showed a tendency toward high activity in metastatic recurrent cases. ERCC1 is said to reduce sensitivity to platinum-based medications. Based on these results, further observation of the progress of treatment in each case is intended.