bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic markers of time to local recurrence and overall survival in early-stage rectal cancer.
Authors: Patel Sagar A , Chen Yu-Hui , Hornick Jason L. , Catalano Paul J. , Nowak Jonathan , Zukerberg Lawrence R. , Hong Theodore S. , Mamon Harvey J. 
Published: February 2017

473 Background: Surgical resection without adjuvant therapy results in a low recurrence rate for patients with early stage (i.e. T1-2 N0) rectal cancer, in the range of 4-15% at 5 years. There are limited data regarding clinical or pathologic markers that are prognostic for recurrence in this population. This study assesses factors associated with time to local recurrence (TTLR) and overall survival (OS) in these patients. Methods: From 2000 to 2008, 177 patients with stage I rectal cancer treated with surgery alone were identified. Data were retrospectively reviewed to identify markers associated with TTLR and OS, including staging method, preoperative CEA, type of surgery, tumor size, lymph node resection, histological grade, circumferential resection margin, and presence of lymphovascular invasion (LVI), lymphocytic infiltration, or ulceration on pathology. Data were analyzed using a Cox proportional hazards regression model. Results: Of the eligible cohort, 137 patients had complete follow up data for analysis of TTLR, and 23 (16.8%) locally recurred. Among these 23 patients, the median TTLR was 1.1 years (0.1-7.8). On univariate analysis, male gender, current alcohol use, LVI and tumor ulceration were associated with heightened risk for LR, and male gender (HR 3.3, p=0.02), current alcohol use (HR 3.4, p=0.01) and tumor ulceration (HR 4.2, p=0.001) remained statistically significant on multivariate analysis. Of the original cohort, 173 patients had complete follow up for OS analysis. Among these patients, the median OS was 12 years. On univariate analysis, age at diagnosis > 65 years, T2 pathologic stage, and tumor size > 4.5 cm were associated with decreased OS, and age at diagnosis > 65 years (HR 2.1, p=0.04) and T2 pathologic stage (HR 2.5, p=0.008) were predictors of reduced OS on multivariate analysis. Conclusions: For patients with stage I rectal cancer treated with surgery alone, male gender, current alcohol use, and tumor ulceration are poor prognostic markers for TTLR. Within this population, age at diagnosis > 65 years and T2 pathologic stage are predictive for reduced OS. These results provide important prognostic information for patients and may help identify those who could benefit from additional therapy.
Randomized phase II study of mixing steroid to reduce venous pain in patients with colorectal cancer receiving oxaliplatin through peripheral vein (APOLLO study).
Authors: Hata Taishi , Toyokawa Akihiro , Kobayashi Michiya , Miyake Masakazu , Tsuda Masahiro , Tobimatsu Kazutoshi , Okamoto Ken , Tokunaga Yukihiko , Takase Kozo , Morita Satoshi , Sakamoto Junichi , Mishima Hideyuki 
Published: February 2017

474 Background: Although theCapeOX (capecitabine+oxaliplatin) regimen obviates the need for a central venous port, administration of oxaliplatin through peripheral vein can cause venous pain. One of the reasons is pH. The pH level of oxaliplatin solution is about 4.8 and that of buffered by steroid is approximately 7.0. To test the hypothesis that adjusting the pH of oxaliplatin solution by mixing steroid can reduce venous pain, we have conducted the randomized control study to compare pH-adjusted oxaliplatin solution with unadjusted oxaliplatin solution. Methods: This was a single-blinded multicenter randomized phase II study. Colorectal cancer patients receiving oxaliplatin through peripheral vein were enrolled and randomly assigned to arm A (oxaliplatin 130 mg/m2 with dexamethasone (DEX) 2 mg) or arm B (the same, without DEX) (UMIN000004286. Venous pain was evaluated according to CTCAE criteria (ver. 4.0) and the verbal rating scale (VRS). Assessments were conducted every 3 weeks until cycle 4. Results: A total of 53 patients (38 men and 15 women; median age, 67 y.o.) were enrolled at 9 institutions in Japan. Of these, 47 evaluable patients were randomized to either arm A (n = 24) or arm B (n = 23). The incidence of venous pain (grade ≥ 2) was 33.3% in arm A and 60.9% in arm B (relative risk 0.55; p = 0.082). The venous pain (VRS score ≥ 3) was 12.5% in arm A and 26.1% in arm B (relative risk 0.48; p = 0.286). No difference was observed in response rate and safety. Conclusions: Adjusting the pH of oxaliplatin solution by addition of a low dose of DEX reduced severe venous pain without influence on response rate and safety. Clinical trial information: UMIN000004286. [Table: see text]
Ultra-staging of node negative (pN0i-) colon cancer: Preliminary results of an international prospective clinical trial.
Authors: Bilchik Anton J. , Nissan Aviram , Protic Mladjan , Wainberg Zev A. , Wasserberg Nir , Avital Itzhak , Stojadinovic Alexander 
Published: February 2017

484 Background: We recently reported in a prospective randomized trial that ultra-staging of patients with colon cancer is associated with significantly improved disease-free survival (DFS) compared with conventional staging (Ann Surg, Sept 2012). This trial was not controlled for lymph node (LN) number, nor use of adjuvant chemotherapy. Methods: The purpose of the present trial, “Ultra-staging in Early Colon Cancer” (UECC) NCI Clinical Trial #00949312 is to evaluate prospectively whether the 12-LN quality measure with ultra-staging impacts DFS without adjuvant chemotherapy. Eligibility criteria included: a) biopsy-proven colon adenocarcinoma; b) no evidence of metastatic disease; c) ≥ 12 LNs staged pathologically; d) pan-cytokeratin immunohistochemistry(IHC) of H&E-negative LNs; d) no adjuvant chemotherapy. The accrual goal is 300 patients with minimum three-year follow-up. Results: To date 126 patients have been accrued with mean and median follow-up of 40 months; 30 didn’t meet the ≥12-LN threshold. Of 52 males and 74 females, 23, 24, and 66 had T1, T2, T3 tumors, respectively. Ninety-six patients had ≥12 H&E and IHC negative LNs (pN0i-). Thirty patients were <12 LNs/pN0i-. Three-year DFS for all patients was 95%. Three-year DFS for patients with ≥12 LNs and pN0i- was 98% compared with 84% for <12 LNs / pN0i- (p=0.002). Three-year DFS differed significantly according to nodal yield in pN0i- patients: 96% vs. 80%, ≥12 vs. <12 LNs, respectively, p=0.03. Conclusions: This is the first prospective trial to demonstrate that adjuvant chemotherapy does not offer any disease-free survival benefit if patients have ≥12LNs ultra-staged by both H&E and IHC (pN0i-). Both surgical and pathological quality measures are essential in the planning of adjuvant chemotherapy trials in node-negative colon cancer. Clinical trial information: NCT00949312.
A phase II trial of salvage treatment with gemcitabine and S-1 combination in heavily pretreated patients with metastatic colorectal cancer.
Authors: Sym Sun Jin , Hong Junshik , Ahn Hee Kyung , Park Jinny , Cho Eun Kyung , Lee Jae Hoon , Lee Won-Suk , Baek Jeong-Heum , Park Yeon Ho , Shin Dong Bok 
Published: February 2017

488 Background: We conducted a phase II trial of gemcitabine with S-1 to evaluate the activity and toxicity of such a combination in heavily pre-treated patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after treatment with 5-fluorouracil (5-FU), oxaliplatin and irinotecan. Methods: 34 pts were enrolled, with the following characteristics: 17 (50%) females, median age 57 years (28-72), 28 (82%) ECOG PS 0-1. S-1 was given orally (30 mg/m2) b.i.d for 14 consecutive days and gemcitabine (1000 mg/m2) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of 9 cycles. The primary endpoint was objective response rate (ORR). Results: The median number of cycles was four (range 1-9). ORR was 14.7% (95% confidence interval [CI] 2.8-26.6) and disease control rate was 58.8% (95% CI 42.2-75.3) with five partial responses and fifteen stable diseases. Median duration of disease control was 5.1 months (95% CI 3.3-7.0). Median progression-free survival was 3.2 months (95% CI 2.3-4.1) and median overall survival was 11.8 months (95% CI 7.0-16.5). Grade 3-4 toxicities were neutropenia (12%), anemia (12%), thrombocytopenia (3%) and diarrhea (3%). Conclusions: Combination chemotherapy with gemcitabine and S-1 was well tolerated and efficacious for heavily pre-treated mCRC pts, and could be an alternative for pts with good PS but no further treatment options.
Clinicopathologic significance of expression of nuclear factor kappa Β and vascular endothelial growth factor in gastric cancer patients.
Authors: Park Keon-Woo , Kwon Hyuk-Chan , KIm Su-Jin , Lee Hyung-Sik 
Published: February 2017

50 Background: Nuclear factor-κB (NF-κB) and vascular endothelial growth factor (VEGF) are involved in cell proliferation, invasion, angiogenesis and metastases. The principal objective of this study was to assess the prognostic significance of NF-κB and VEGF expression in gastric cancer Methods: The tumor tissues of 154 patients with gastric cancer, all of whom underwent potentially curative resection, were immunohistochemically evaluated using monoclonal antibodies against NF-κB and VEGF. Results: Positivity rates of NF-κB and VEGF were 44.2% and 39.6%, respectively. NF-κB expression in tumor tissues was correlated significantly with VEGF expression (p < 0.001). VEGF expression was related to Lauren’s classification (p = 0.002), differentiation (p = 0.043), depth of invasion (p = 0.005), carcinoembryonic antigen (p = 0.032), and stage (p = 0.026). However, NF-κB expression was not related to any of these parameters. Univariate analysis demonstrated that NF-κB expression was significantly related with both 5-year disease free survival (65.2% vs. 46.4%, p = 0.007), and 5-year overall survival (60.0% vs. 42.5%, p = 0.014). Multivariate analysis verified that NF-κB was independently associated with disease free survival (hazard ratio: 2.082, p = 0.005), and overall survival (hazard ratio: 1.841, p = 0.008). However, VEGF did not appear to be related to adverse clinical outcome. Conclusions: NF-κB expression in tumor tissue is associated with poor survival in gastric cancer patients.
Outcomes in patients (pts) with colorectal cancer (CRC) treated with oxaliplatin-based chemotherapy (OC) following prior oxaliplatin exposure.
Authors: Bhadkamkar Nishin Anil , Sahin Ibrahim Halil , Shen Yehua , Hassabo Hesham Mohamed , Kee Bryan K. , Hassan Manal , Garrett Chris R. 
Published: February 2017

500 Background: Pts frequently treated with OC in the adjuvant, perioperative, or first-line setting for CRC may be retreated with oxaliplatin at the time of relapse or progression; the efficacy of retreatment is not known. Methods: Under an IRB-approved protocol, the pharmacy records identified 1,166 pts who received OC for CRC at our institution from 1/1/2004-12/30/2009. Pts were categorized as having previously received OC initially for the indication of adjuvant (group A, n=29), unresectable metastatic disease (group B, n=75), or perioperative therapy for metastasectomy (group C, n =22). Results: Four RECIST responses (14%) were seen in group A (2 of these pts received cetuximab in combination), four responses in group B (5%), and no responses in group C. Retreatment with OC following initial oxaliplatin exposure was associated with a low radiographic and biochemical response rate and a short time to progression or withdrawal of OC (Table). Retreatment duration was limited by cumulative neurotoxicity and allergic reactions (data not presented). Significant activity was observed more frequently when a novel biologic agent was added to the pt's treatment. Conclusions: Retreatment with OC demonstrated minimal clinical efficacy and is limited by cumulative neurotoxicity and hypersensitivity reactions. [Table: see text]
Effect of primary tumor resection on survival in patients with metastatic colorectal cancer in the post-2000 era: A California Cancer Registry analysis.
Authors: Rodriguez Fahrni Ana Milena , Gong I-Yeh , Chen Yingjia , Cress Rosemary , Semrad Thomas John , Khatri Vijay P. 
Published: February 2017

504 Background: Resection of primary tumors in the setting of metastatic colorectal cancer (MCRC) is controversial. Fewer primary tumor resections are being performed due to the improved tumor response and disease control rates associated with modern systemic therapy. Recent studies suggest a survival benefit for patients with MCRC who had primary tumors resection prior to systemic therapy. This analysis evaluates the independent prognostic impact of primary tumor resection on overall survival (OS) for patients with MCRC using the California Cancer Registry (CCR). Methods: We queried the CCR for all patients with MCRC diagnosed between 2003 and 2010. Patients were categorized by whether or not they had primary tumor resection at time of diagnosis. Covariates included gender, age, race/ethnicity, socioeconomic status (SES), and rural-urban commuting area (RUCA) score of patients. Univariate comparisons were made using the Kaplan Meier method. Multivariate comparisons were performed using the Cox proportional hazards regression method. Results: 19,836 patients met the criteria for analysis of whom 11,566 (58%) had primary tumor resection. Primary tumor resection rates declined over this time period (63% in 2003 v. 52.8% in 2010, p<0.0001), varied by SES (55% v. 62%: lowest versus highest, p<0.001) and residence (63% in rural versus 58% for urban, P=0.0160). On multivariate analysis, overall survival was significantly better for patients that had primary tumor resection (HR: 0.467 [95% CI: 0.467-0.482]; p<0.0001). Survival was statistically longer in younger patients (HR: 1.385 for age 65-75, HR: 2.217 if greater than age 75), highest SES (HR: 0.869, p<0.0001), Hispanics (HR: 0.884, p<0001), and Asian/Pacific Islanders (HR:0.892, p<0.0001). Overall survival was worse for African Americans (HR:1.105, P=0.0001). Conclusions: Our study demonstrates the independent prognostic value on survival of primary tumor resection in patients with MCRC. There is significant variability of resection rates by SES and rural-urban residence. As analysis of CCR data cannot eliminate the influence of patient and provider biases, a prospective randomized trial is warranted.
Impact of relative dose intensity on the outcome of metastatic colorectal cancer.
Authors: Nakayama Goro , Asada Takahiro , Hayashi Naomi , Tanaka Chie , Yamada Suguru , Fujii Tsutomu , Koike Masahiko , Fujiwara Michitaka , Kodera Yasuhiro 
Published: February 2017

508 Background: Relative dose intensity (RDI) is the ratio of delivered dose intensity of chemotherapy to standard dose intensity. There is established evidence supporting the significance of RDI in patients with various cancer, however data in patients with metastatic colorectal cancer (mCRC) are limited. In this study, we evaluate the significance of RDI of irinotecan and oxaliplatin-based chemotherapy on the outcome of mCRC. Methods: A retrospective analysis of mCRC patients entered into two prospective clinical trials, testing FOLFIRI (CCOG-0502) and mFOLFOX6 (CCOG-0704), was performed. RDI was calculated as the delivered dose intensity divided by standard dose intensity calculated for each regimen and compared to objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS). Results: The median RDI of irinotecan in FOLFIRI and oxaliplatin in mFOLFOX6 were 80% and 79%. ORRs In higher RDI (>median) group and lower RDI (<median) group were 64.7% and 5.9% of irinotecan (p=0.001), and 46.7% and 33.3% of oxaliplatin (p=0.456). DCRs in higher and lower group were 100% and 41.2% in FOLFIRI (p=0.003), and 100 and 73.3% in mFOLFOX6 (p=0.032). PFS in higher and lower group were 9.9 and 5.6 months in FOLFIRI (p=0.002), and 8.5 and 6.2 months in mFOLFOX6 (p=0.064). Conclusions: RDI of key cytotoxic agents is a significant predictor of disease control in patients with mCRC, especially in irinotecan-based regimen. Dose reductions and treatment delays could be minimized to achieve an RDI of at least 80%.
Time from surgery to first adjuvant chemotherapy: Experiences at an inner-city Canadian hospital.
Authors: Marchand Christina , Hassan Maha , Ebrahim Jalal , Bookwala Ammar , Sevick Laura , Ansari Ata , Wong Audrey , Hogeveen Sophie , Nisenbaum Rosane , Topic Delilah Lisa , Brezden-Masley Christine 
Published: February 2017

527 Background: Cancer Care Ontario (CCO) guidelines advise that colorectal cancer (CRC) patients receive their first adjuvant chemotherapy (AC) no later than 8 weeks after surgical resection, with new data suggesting optimal treatment to commence between 4 and 6 weeks. This retrospective study was performed to determine treatment timelines and identify barriers at St. Michael’s Hospital (SMH). Methods: Of the 507 patients diagnosed with CRC between Jan 1, 2005 and May 1, 2012 at SMH, 304 patients had stage II or III CRC. Our sample population of 159 patients received both surgical resection and AC at SMH. Data collected included: time between surgery and first AC, patient demographics, systemic/clinical barriers and recurrence-free survival. Data was analyzed using SAS statistical software assuming p-values <0.05 as significant. Results: Of our 159 patients, mean age was 61.3 years (range 28 – 91); 54% male and 70% had stage III disease; colon cancer (64%) and mean follow-up was 2.2 years (range 0.1 – 5.7). Mean time from surgery to first AC was 50.4 days (sd = 15.8) or 7.2 weeks ranging from 3 to almost 17 weeks. Medical complications affected 21.4% of patients. The presence of a complication was associated with delay in AC (9.5 days, p=0.001). Moreover, 11.1% of patients were excluded from sample, since complications exceeded treatment past 12 weeks, equating to no AC. Referral from surgeon averaged 21 days (sd=12.0), 10 days awaiting pathology. Medical Oncology consult to first AC averaged 19 days (sd=12.7), 12 days awaiting port-a-cath insertion. Each part of referral process was correlated with delay to AC. Only 18.9% of patients recurred. While trends were identified, association between delay and recurrence was weak (p=0.1457). Medical complication correlated strongly with recurrence (p=0.0472). Patients with complications had a higher rate of recurrence (32.4% vs 15.2%). Conclusions: Compliance to current CCO guidelines can be optimized in CRC patients at SMH. Barriers to timely treatment include patient age, timely referral and presence of a medical complication. Quality improvement rapid cycling of confounding barriers will be used prospectively to lower variance and achieve greater consistency in treatment.
Skin toxicity and treatment compliance of first-line cetuximab with irinotecan, oxaliplatin, and fluoropyrimidines-based chemotherapy in metastatic colorectal cancer (mCRC): The preliminary analysis of observer study.
Authors: Pinto Carmine , Rosati Gerardo , Lolli Ivan , Ruggeri Enzo , Ciuffreda Libero , Ferrari Daris , Di Fabio Francesca , Chiara Silvana , Tralongo Paolo , Ianniello Giovanni Paolo , Frassoldati Antonio , Tumolo Salvatore , DI Costanzo Francesco 
Published: February 2017

530 Background: The ObservEr study evaluated the quality of life (QoL), skin toxicity control and treatment compliance of cetuximab plus first-line chemotherapy in a general cohort of patients with mCRC. Methods: ObservEr is a non interventional, observational, multicenter, prospective study. The primary end point is the evaluation of change in QoL during the period in which a first line treatment chemotherapy is given, with specific focus on the impact of the dermatological toxicity of this treatment. Data on QoL (Dermatology Life Quality Index/DLQI and EORTC QLQ C30) is assessed at baseline weekly for the first 8 weeks of treatment. Results: Between April 2011 and September 2012, the expected 210 patients (pts) were enrolled in 31 Italian centers. This preliminary analysis includes 112 pts enrolled to until April 2012. Pt characteristics were: 77(68.7%) males, 35(31.3%) females; median age 70 years (44-80 years); PS ECOG-0 86(76.8%), ECOG-1 36(23.2%); potentially resectable liver metastasis 32(28.6%); chemotherapy regimen FOLFIRI 55(49.1%), XELIRI 13(11.6%), FOLFOX 22(19.6%), XELOX 10(8.9%), irinotecan 4(3.6%), 5FU/AF (de Gramont) 2(1.8%), others 6(5.4%). The interval time between request and result of KRAS test was 10 days (7-16 days). Prophylactic skin toxicity with vitamin K1 cream was performed in 79(70.5%) pts, and reactive skin toxicity treatment included vitamin K1 cream in 32(28.6%). Grade 1-3 skin toxicity was observed in 87(77.7%) pts, and grade 3 in 10(8.9%). No significant difference in grade 3 skin toxicity was detected between males vs females (10.4 vs 5.7%; p=0.722), age <60 vs ≥60 years (9.7 vs 8.6%; p=1.000), and prophylactic vs reactive treatment (7.6 vs 12.5%; p=0.470). Cetuximab temporary and permanent discontinuation relation to skin toxicity was observed in 15(13.4%) and 2(1.8%) pts, respectively. Conclusions: This results suggest that the introduction of K1 cream in the prophylactic or reactive treatment reduce the incidence of grade 3 skin toxicity with improvement of cetuximab compliance. The results of QoL will be available for the 2013 ASCO GI Meeting. Clinical trial information: ID239.
Locally recurrent colorectal cancer and hepatic metastases: Safety, feasibility, and outcomes after concomitant resection.
Authors: Boostrom Sarah York , Mathis Kellie Leanne , Dozois Eric J. , Nagorney David , Cima Robert R , Larson David W , Wolff Bruce G. , Pemberton John H 
Published: February 2017

535 Background: The most effective management of locally recurrent colorectal cancer (CRC) is resection. This is also true for hepatic metastases (HM). Data remains limited, however, regarding concomitant resection of recurrent CRC and HM. The aims of this study were to determine the feasibility, safety and outcomes in terms of disease-free survival (DFS) and overall survival (OS) in patients undergoing concomitant resection of recurrent CRC with HM. Methods: All patients who underwent resection of recurrent CRC from 1/1995 to 1/2007 at Mayo Clinic, Rochester were reviewed (n=406). The study group consisted of patients who underwentconcomitant resection of locally recurrent CRC and hepatic resection for metastatic CRC (n= 45). Kaplan-Meier Survival was used to estimate DFS and OS. Results: The study group consisted of 27 men and 18 women. The median age was 59 years. Surgical management involved pelvic dissection in 43 patients and ileotransverse colectomy in two. 17 patients required resection of contiguous organs. 24 patients received intra-operative radiation. 34 patients underwent multiple hepatic wedge resections, 6 patients segmentectomy, 3 left hepatectomy, and 2 right hepatectomy. There was no perioperative mortality. Morbidity was 37%, 2 patients required re-operation. The 1, 3, and 5 year DFS was 72.2, 42.3, and 18.5%, respectively. The 1, 3, and 5 year OS was 87.7, 47.6, and 36.2%, respectively. Conclusions: Synchronous resection of locally recurrent CRC and HM is safe and feasible; morbidity is reasonable and mortality zero. DFS and OS in this patient population appear comparable to that of patients undergoing separate, staged resections.