bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prognostic nomogram for predicting recurrence and survival in rectal cancers without neoadjuvant treatment.
Authors: Peng Junjie , Ding Ying , Wu Hongbin , Cai Sanjun 
Published: February 2017

555 Background: To develop a prognostic nomogram for predicting recurrence and survival in patients with locally advanced rectal cancers that were not able to receive preoperative treatment. Methods: A total of 887 patients with AJCC (7th edition) stage II-III rectal cancers were retrospectively collected from a single institution. All patients did not receive any preoperative treatment before curative resection of the primary tumor. Cox proportional hazards model was performed to develop the predictive model for OS. Results: The 5-year local recurrence rate, distant metastases rate, and overall survival rate were 22.2%, 32.9%, and 63.9%, respectively. A prognostic nomogram was successfully developed to predicting patients’ 5-year overall survival, with a concordance index of 0.7. Factors in this model included patients’ age, gender, CEA value, tumor location, T stage, N stage, metastatic lymph nodes ratio, lymphvascular invasion, perineural invasion, adjuvant chemotherapy, adjuvant chemoradiotherapy. Our nomogram improved the predicting accuracy of current AJCC stage system (7th edition). Conclusions: The prognostic nomogram integrated patients demographic and clinicopathologic factors, which is better able to account for tumor and patient heterogeneity. Our individualized prediction nomogram could help physicians counsel and advise patients about their personalized treatment strategies and follow-up protocols. [Table: see text]
Ziv-aflibercept (Z) in combination with FOLFIRI for second-line treatment of patients (pts) with metastatic colorectal cancer (mCRC): Interim safety data from the global aflibercept safety and quality-of-life program in pts pretreated with bevacizumab (B).
Authors: Ferry David Raymond , Sobrero Alberto F. , Bordonaro Roberto , Siena Salvatore , Pietrantonio Filippo , Bauer Stefan , Taïeb Julien , Garreau-Laporte Pascale , Brette Sandrine , Dochy Emmanuelle , Lledo Gérard 
Published: February 2017

556 Background: In the VELOUR study, adding Z (known as aflibercept outside the United States) to FOLFIRI resulted in improved OS, PFS, and RR in mCRC pts who had received prior oxaliplatin. Prior treatment with B (~30% of the ITT population) did not appear to impact the safety profile of Z. Results from VELOUR supported initiation of the global Aflibercept Safety and Quality-of-Life (QoL) Program composed of two clinical studies (ASQoP [NCT01571284]; AFEQT [NCT01670721]) to capture QoL and safety data from a population similar to that of VELOUR in a real-life setting. We report early safety data from this interim analysis in pts pretreated with B. Methods: ASQoP and AFEQT are single-arm, open-label trials evaluating safety and QoL of Z in mCRC pts previously treated with an oxaliplatin-containing regimen. Eligible pts receive Z (4 mg/kg) q2wks on day 1 of each cycle followed by FOLFIRI until disease progression, unacceptable toxicity, death, or investigator/pt decision. Initial starting doses and subsequent modifications are at treating physicians’ discretion. The percentage of pts with grade (G) 3/4 adverse events (AEs) in the combined safety population of ASQoP and AFEQT in B-pretreated pts is compared with that of B-pretreated pts in VELOUR. Results: At data cut-off, the safety population comprised 116 pts with ≥1 completed treatment cycle; 67 (57.8%) were pretreated with B. At least 1 G3/4 AE was experienced by 49.3% of pts vs 82.5% in VELOUR. Most G3/4 AEs were G3. There were no reports of G4 hypertension or proteinuria. Conclusions: Thisinterim safety analysis from ASQoP/AFEQT in pts pretreated with B has identified no new safety signals for Z and a trend toward decreased incidence of G3/4 events. The early analysis provides additional safety data and suggests an acceptable toxicity profile in this real-life setting. Clinical trial information: NCT01571284. [Table: see text]
Inhibition of migration and invasion of gastric cancer cells by Snail-regulated MiR-375 through JAK2 targeting.
Authors: Yanjun Xu , Tianhua Zhou , Jianmin Si , Wei Zhuo 
Published: February 2017

56 Background: Migration and invasion of cancer cells are essential process during cancer metastatic procession. In gastric cancer, cells invasion into the surrounding tissue is a crucial early step. However, the mechanisms have not been fully understood. MicroRNAs, which are a class of small single-stranded non-coding RNA, participate in the malignant progressions of cancer, including metastasis. We study the association between specific dysregulated miRNA and specific metastasis step of gastric cancer, which will provide insights into the potential mechanisms of gastric cancer cells migration, invasion and metastasis. Methods: The expression of miR-375 was assayed using the quantitative real-time PCR analysis. Scratch-wound healing assay, Transwell migration and invasion assay were conducted to study the migration and invasion abilities of cells. Animal experiment was also conducted to examine the effect on liver and lung metastases by overexpression of miR-375. Luciferase assay was conducted to study the association between Snail and miR-375. Results: MiR-375 is downregulated in gastric cancer cells with greater migration and invasion abilities. The expression level of miR-375 is decreased in gastric cancer tissues from metastasis-positive patients compared with that from metastasis-free patients. Overexpression of miR-375 inhibits the migration and invasion abilities of gastric cancer cells. JAK2, which may be a target gene of miR-375, could reverses miR-375 induced inhibition of gastric cancer cells migration and invasion. Liver metastasis was not detected in mice injected with miR-375 overexpressed cells but was apparent in mice injected with cells which were transfected with control vector. The transcription factor Snail, which binds directly to the putative promoter of miR-375, could reduce the expression level of miR-375 significantly. A distinct inverse correlation was found between miR-375 expression and Snail mRNA level. Conclusions: These findings demonstrate that tumor suppressor miR-375, whose expression is directly regulated by the transcription factor Snail, inhibits gastric cancer cells migration, invasion and metastasis by targeting an important protein JAK2.
Use of preoperative tattooing to increase lymph nodes (LNs) retrieved in patients with locally advanced rectal cancer who receive preoperative chemoradiotherapy (CRT): A randomized controlled trial.
Authors: Okada Kazutake , Sadahiro Sotaro , Suzuki Toshiyuki , Tanaka Akira , Saito Gota , Kamijo Akemi 
Published: February 2017

561 Background: Retrieval of 12 or more LNs has been recommended for accurate staging of colorectal cancer. Patients with 12 or more LNs revealed better survival than those with less than 12 LNs. Preoperative tattooing has been reported to improve LNs retrieval in colorectal cancer. Preoperative CRT had been reported to decrease the number of LNs in rectal cancer. We conducted a randomized controlled study to validate whether preoperative tattooing increases the number of LNs in patients who receive preoperative CRT. Methods: Fifty patients with cStage II or III rectal cancer were randomly assigned to a group in which tattooing was performed at the time of colonoscopy one day before surgery (T group) or a group without tattooing (C group). Submucosal injection of India ink was performed into two sites at the lower tumor margin. All patients had received 40/45 Gy of radiotherapy in 20/25 fractions with concurrent oral UFT or S-1 chemotherapy. Mesorectal excision was performed 6 to 8 weeks after completion of CRT. Results: There were no significant differences in characteristics between the groups. The numbers of retrieved LNs (mean±SD) in T group and C group were 14±7 and 8±6, respectively (p < 0.01). The number of patients with 12 or more LNs was greater in T group (56%) than in C group (20%) (p < 0.01). The numbers of metastatic LNs were similar in both groups (0.5±1.2 and 0.5±1.4, respectively p = 0.92). In patients with poor histologic tumor regression (TRG grade 3 to 5), the number of LNs was significantly greater in T group (17±9) than in C group (6±5; p < 0.01). However, in patients with good histologic response (TRG grade 1 or 2), the numbers of LNs in T group and C group were 11±5 and 9±6, respectively (p = 0.31). In T group, the numbers of LNs and metastatic LNs were significantly greater only in patients with poor histologic regression. Conclusions: Preoperative tattooing increases the number of retrieved LNs. In patients with poor histologic response following CRT, tattooing significantly increases the numbers of LNs. However, tattooing does not increase the numbers of retrieved LNs and metastatic LNs in patients with good histologic response. Clinical trial information: 11R-004.
Safety and efficacy of bevacizumab and systemic therapy in metastatic colorectal cancer (mCRC) patients with peritoneal disease in the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) database.
Authors: Roohullah Aflah , Wong Hui-li , Sjoquist Katrin Marie , Field Kathryn Maree , Tran Ben , Shapiro Jeremy David , McKendrick Joseph James , Yip Desmond , Nott Louise M. , Gibbs Peter , Chantrill Lorraine A. 
Published: February 2017

569 Background: Patients (pts) with peritoneal metastases from CRC are considered a poor prognostic group. Data on safety and efficacy of systemic chemotherapy and bevacizumab (BEV) in these pts are limited. Of particular concern peritoneal disease has been reported to increase the risk of GI perforation in pts treated with BEV. Methods: TRACC is a prospective, multisite, mCRC registry with data collection ongoing at 14 Australian hospitals since July 2009. Data related to baseline demographics, treatment and outcomes were extracted and differences between pts with and without peritoneal disease were examined. Results: 1,012 pts were identified, median age 68 years (range 19-97), 179 (17.7%) had peritoneal disease at diagnosis; median follow up was 20.9 months (m). In pts with peritoneal disease there were a higher proportion of pts with poor ECOG (2-4) 30.2% vs. 17.1% p = 0.0002; colon primary 87.7% vs. 66.7% p < 0.0001; and multiple disease sites p < 0.0001. A similar proportion received chemotherapy in the peritoneal group 136/179 (76.0%) compared to the non-peritoneal group 619/833 (74.3%). In the peritoneal group 90/136 (66.2%) received BEV. For patients with peritoneal disease the addition of BEV to chemotherapy was associated with an improved PFS 8.6m vs. 5.1m (HR = 0.62 95%CI 0.40-0.96 p = 0.034) and OS 18.7m vs. 12.1m (HR = 0.59 95%CI 0.36-0.96 p = 0.032) compared to chemotherapy alone. On univariate analysis the proportional benefit from the addition of BEV was similar to the non-peritoneal group. GI perforation was not increased in BEV-treated pts with peritoneal disease 2/90 (2.2%) vs. 8/332 (2.4%) without peritoneal disease, p = 1.000. Conclusions: In routine clinical practice, clinicians appear comfortable prescribing BEV in the presence of peritoneal disease. The addition of BEV to chemotherapy in these pts appears to be safe, with no apparent excess risk of GI perforation, and is associated with an improved PFS and OS. Multivariate analyses are planned.
A phase I/II study of cetuximab (cet) in combination with S-1 and oxaliplatin (SOX) in first-line treatment for metastatic colorectal cancer (mCRC) (JACCRO CC-06).
Authors: Tsuji Akihito , Sunakawa Yu , Denda Tadamichi , Takinishi Yasutaka , Kotaka Masahito , Tanioka Hiroaki , Shimada Ken , Kochi Mitsugu , Watanabe Takanori , Nakamura Masato , Ueda Hiroto , Inukai Michio , Masuishi Toshiki , Tani Satoshi , Negoro Yuji , Okuno Tatsuya , Takeuchi Masahiro , Ichikawa Wataru , Fujii Masashi , Nakajima Toshifusa 
Published: February 2017

571 Background: Both SOX and cet are effective treatments each other in patients (pts) with mCRC. COIN trial indicated that the use of cet in combination with capacitabine and oxaliplatin should not be recommended. However, the safety and efficacy of cet plus SOX are not clear. To evaluate the safety and clinical efficacy of the combination, we conducted a multi-center phase I/II study. Methods: In this trial, we assigned pts with KRAS wild type (wt), EGFR-expressing tumor and no prior chemotherapy to receive cet (initial dose 400, and 250 mg/m2 weekly) followed by SOX (oxaliplatin on day 1 and S-1 40 mg/m2 twice daily on days 1-14). The treatment was repeated every 3 weeks. The phase I part was designed to determine the maximum tolerated dose (MTD) and recommended dose (RD) according to the dose adaptation schedule of oxaliplatin (100 mg/m2 for level 1 and 130 mg/m2 for level 2). In the following phase II part, the enrolled pts were treated with the RD. The primary endpoint was response rate (RR) evaluated by the external review board according to RECIST criteria v1.1. Secondary endpoints included PFS, OS, and safety. In addition, we prospectively evaluated early tumor shrinkage (ETS). Results: A total of 67 pts were enrolled from January 2012 to February 2013. In the phase I part, level 2 was determined to be the RD. The MTD was not determined because dose limiting toxicity was not confirmed in level 2. In the phase II part, 59 pts including 6 pts of phase I cohort were assessable for the efficacy. The median age was 64 years, 51% of pts were male, and ECOG PS 0 was observed in 85% of pts. The median course of treatment was 5 (range 1-14). The RR was 62.7% (95%CI, 50.4 to 75.1) and ETS was observed in 72% of pts. In safety analysis, grade 3 or worse adverse events were platelet count decreased (13.1%), neutropenia (8.2%), anorexia (11.7%), rash acneform (6.7%) and peripheral neuropathy (3.3%). Conclusions: We determined the RD of cet plus SOX treatment in pts with mCRC. This combination is tolerable at full doses of cet and SOX, with manageable toxicities, and demonstrates advantages in RR for pts with KRAS wt tumor. Updated safety and efficacy data will be presented. Clinical trial information: UMIN000007022.
Dietary and behavioral adjustments to control bowel function by long-term colorectal cancer survivors.
Authors: Sun Virginia , Grant Marcia , Wendel Christopher S. , McMullen Carmit K. , Bulkley Joanna E. , Altschuler Andrea , Ramirez Michelle L. , Baldwin Carol M. , Rawl Susan , Herrinton Lisa J. , Hornbrook Mark C. , Krouse Robert S. 
Published: February 2017

573 Background: Bowel dysfunction is a known complication of colorectal cancer (CRC) treatment, and has a detrimental impact on survivors’ health-related quality of life (HRQOL). The prevalence of dietary and behavioral modifications in CRC survivors has been described in only a small number of studies. To better understand dietary and behavioral adjustments that long-term (≥ 5 years) CRC survivors make to regulate their bowel function, we performed a mixed methods analysis, comparing survivors with a permanent ostomy and those with anastomosis. Methods: CRC survivors with or without permanent ostomies were surveyed with the modified version of the City of Hope Quality of Life for Ostomy tool (N=919).Dietary adjustments were compared by ostomy status (ostomy versus anastomosis) and higher quartile versus lower quartile HRQOL scores.Student’s t-tests were used to compare HRQOL measures between groups. Qualitative data from 13 focus groups (N=63) and interviews with 30 female ostomates were analyzed to explore specific strategies used for regulating bowel function. Results: CRC survivors make substantial andpermanent dietary adjustments following treatment. The majority of survivors reported that they took more than one month to feel comfortable with their diet, and many (10% to 18%) never became comfortable. No significant dietary adjustment differences were noted based on ostomy status. Survivors who took less time (<1 month) to feel comfortable with their diet and for their appetite to return had better HRQOL (p < 0.001) ≥ 5 years later. Adjustments to control bowel function consisted of four overall strategies: dietary adjustments, behavioral adjustments, exercise, and medications. Conclusions: CRC survivors use a multitude of adaptive strategies to control their bowel function. Many survivors struggle with unpredictable bowel function continually for the rest of their lives, and many never find any set of management strategies to achieve regularity. Understanding the myriad of adjustments made by CRC survivors will lead to evidence-based recommendations to foster positive adjustments after cancer treatment.
A phase II clinical trial of preoperative chemoradiotherapy (CRT) with oral S-1 plus bevacizumab in patients with middle or lower rectal adenocarcinoma.
Authors: Sadahiro Sotaro , Suzuki Toshiyuki , Tanaka Akira , Okada Kazutake , Saito Gota , Kamijo Akemi 
Published: February 2017

575 Background: Preoperative CRT decreases local failure and increases sphincter preservation in patients with clinical stage II or III rectal cancer. Patients with ypCR after CRT reveal better oncologic outcomes. S-1 is an oral fluoropyrimidine with radiosensitizing activity. We previously reported preoperative CRT with S-1 was effective (ypCR 22.2%) and safe (Oncology 2011). Combining bevacizumab with 5-FU- or capecitabine-based CRT had been reported to provide promising results. We evaluated the effectiveness and safety of bevacizumab plus S-1-based CRT. Methods: The subjects were 46 patients with clinical stage II or III adenocarcinoma of the mid or low rectum enrolled from Feb. 2011 through May 2013. Pelvic radiotherapy was given in a total dose of 45 Gy, delivered in 25 factions. S-1 (80 mg/m2/day) was given orally twice daily for a total of 28 days during weeks 1, 2, 4, and 5. Bevacizumab (5 mg/kg) was administered a total of 3 times at day 1, 15, and 29. Mesorectal excision was performed 6 to 8 weeks after the completion of CRT. The primary endpoint was the ypCR rate. Secondary endpoints were the degree of tumor shrinkage, sphincter-preservation rate, and safety. Results: Clinical stage was II in 13 patients and III in 33. The median interval from the completion of CRT to surgery was 8 weeks (range, 4 to 9). The ypCR rate was 21.7% (10/46), with a T downstaging rate of 54.3% and an N downstaging rate of 50.0%. The degree of tumor shrinkage was 51.8 ± 16.6% (mean ± SD) on barium enema and 77.7 ± 11.1% on a volumetric analysis based on MRI. The sphincter-preservation rate was 76.1% (35/46). Grade 3 or higher adverse event occurring during CRT was leukopenia in 1 patient (2.2%). Surgery was not postponed because of adverse events in any patient. However, 63.0% of the patients had anal pain (grade 1, 6 patients; grade 2, 23). Postoperative complications occurred in 32.6%: anastomotic leakage in 25.7% (9/35) in LAR and perineal wound dehiscence in 18.2% (2/11) in APR. Conclusions: CRT with S-1 plus bevacizumab had similar antitumor effectiveness and adverse events as CRT only with S-1, but was associated with higher incidences of perioperative complications related to wound healing. Clinical trial information: 10R-113.
Efficacy and safety of single agent (SA) or combination (CO) adjuvant chemotherapy (AC) in elderly patients with colon cancer: A Canadian cancer institute experience.
Authors: Kim Christina , Spratlin Jennifer L. , Ghosh Sunita , Armstrong Dawn Elizabeth , Mulder Karen E. 
Published: February 2017

581 Background: Although AC is recommended for colon cancer, the pattern of AC use in elderly patients (pts), the toxicity profile, & survival benefit is unclear. We sought to (1)determine whether pts ≥ 65 years old with stage III colon cancer were being offered SA or CO AC; (2)evaluate the reason for selecting SA vs. CO AC; (3)evaluate the toxicity profile of SA and CO in the elderly; and (4)determine whether a survival benefit exists for elderly pts receiving CO AC. Methods: Pts ≥ 65 diagnosed with stage III colon cancer at the Cross Cancer Institute from 2004-2010 were identified from the cancer registry. A retrospective analysis of electronic and paper patient records was performed to identify baseline characteristics, AC protocols used, toxicity, dose intensity and survival. Results: 258 pts ≥ 65 years old were diagnosed and treated with AC from 2004-2010. Of these, 168 were treated with SA and 90 with CO AC. The most common reasons for choosing SA AC were patient preference (64%), comorbidities (10%), and lack of drug coverage by provincial formulary (15%). 93 pts ≥age 75 were treated with SA AC, whereas only 10 pts ≥ 75 were treated with CO AC. Multivariate analysis revealed that for each year above 65, the adjusted odds of receiving CO over SA AC decreased by 22%. The presence of cardiac comorbidities decreased the adjusted odds of receiving CO AC by 58%. 28% of pts treated with SA and 6% of those treated with CO AC had initial dose reductions, with most common reasons being comorbidities and age. 67%, 71%, and 29% received dose delays, reductions or drug discontinuation in the SA group, respectively. 72%, 58%, and 34% received dose delays, reductions or drug discontinuation in the CO group respectively, mostly due to hematologic toxicity. The 5 year OS was 73% in pts who received SA AC, compared to 84% in those who received CO AC. A competing risk analysis showed no difference in cancer-related deaths between the CO and SA AC groups. Conclusions: In elderly pts treated with AC for stage III colon cancer, SA AC is used more frequently than CO AC, based on age, comorbidities, and patient choice. Toxicity with CO AC in elderly pts is high, leading to decreased dose intensity. No survival benefit was seen with CO AC over SA AC.
Cost differential among systemic therapies for colon cancer.
Authors: Nadeem Hasan , Jayakrishnan Thejus T. , Gamblin T. Clark , Turaga Kiran 
Published: February 2017

583 Background: The National Comprehensive Cancer Network (NCCN) has outlined recommendations for the treatment of various cancers that incorporates alternative chemotherapeutic strategies presumed to be of similar effectiveness. We hypothesized that there is a significant cost-differential between the therapeutically equivalent systemic therapy regimens for colon cancer. Methods: Details of chemotherapy regimens outlined in NCCN guidelines (2013) were acquired for colon cancer. Costs (US$) were calculated based on the payment allowance for Medicare part-B drugs database (2013). Dosage amounts were calculated for an average American patient and additional costs (treatment time, pumps) were added to determine total treatment costs for 6 months. Results: Total of 25 regimens were studied. The median cost for systemic treatment of metastatic colon cancer for a 6-month period was $34,840 (IQR $9,420-$68,840, n=20). The median cost for adjuvant treatment alone was $13,870 (range $2,600-$33,230, n=5). The cost-differential for a single patient between FOLFOX and Folfiri+ziv-aflibercept was $4.2 million for metastatic colon cancer. The addition of novel antineoplastics dramatically increased the price of chemotherapy (Table). Conclusions: Economically significant cost differential exist between chemotherapeutic regimens prescribed as equally effective. Hierarchical adoption of regimens based on therapeutic benefit, cost and patient-specific toxicity profile may help reduce health care costs. [Table: see text]