bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized, controlled trial comparing UFT with S-1 as adjuvant therapy for curatively resected stage III colorectal cancer.
Authors: Koda K. , Miyauchi H. , Ochiai T. , Yasuda H. , Kaiho T. , Tanaka N. , Yokoi K. , Kobayashi S. , Matsubara H. 
Published: February 2017

515 Background: Oral anticancer drug, UFT, has recently been reported to improve both overall survival (OS) and relapse-free survival (RFS) for patients with stage III colorectal cancer in Japan. We conducted a randomized clinical trial to compare S-1 with UFT for adjuvant therapy in patients with stage III colorectal cancer. Methods: Patients with stage III colorectal cancer (PS, 0 to 1; age, 20 to 80 years) were randomized to take either UFT (400mg/m2/day, 5days per week) or S-1 (80mg/m2/day, 28days per 6weeks) for 1 year started within 6 weeks following curative resection. The primary endpoint was to investigate relations of relapse-free survival (RFS) and tissue mRNA levels of 5-FU metabolism-related enzymes. The secondary endpoint was over all survival (OS) and safety. Results: Between July 2005 and February 2008, a total of 100 patients were registered from 21 centers. There were no clear intergroup differences in background factors. When patients who relapsed within 1 year postoperatively were excluded, the percentages of patients who took expected dosage of medicine were 73% (30/41) and 72% (33/46) in UFT and S-1 groups, respectively. Grade 3 liver dysfunction (4%) or diarrhea (4%) occurred in UFT group, whereas grade3 to 4 myelosuppression (4%), diarrhea (4%), stomatitis (2%) were observed in S-1 group, but all of them were reversible. With a median follow-up period of 1,250 days, OS in patients of UFT and S-1 groups were 86.6% and 95.9%, respectively (p=0.06). The number of patients who relapsed in rectal cancer was significantly higher in UFT group (11/25) than in S-1 group (4/21, p<0.01). In a multivariate analysis, dihydropyrimidine dehydrogenase (DPD) mRNA level was shown as a factor of the recurrences. And S-1 improved RFS in patients with rectum cancer with high orotate phosphoribosil transferase (OPRT) mRNA level. Conclusions: Oral anticancer drug, S-1, was no less effective than UFT as an adjuvant therapy for stage III colorectal cancer. Tissue levels of both DPD and OPRT mRNA were important parameters for postoperative prognosis in patients with stage III colorectal cancer who take oral 5-FU derivatives for adjuvant therapy. No significant financial relationships to disclose.
Reproducibility of colon tumor grade and relationship to recurrence in the context of clinical, pathologic, and genomic tumor features in 504 patients with stage II colon cancer treated with surgery alone at the Cleveland Clinic.
Authors: Lavery I. C. , Baehner F. L. , Lopatin M. , Iezza G. , Millward C. , Clark-Langone K. , Lee M. 
Published: February 2017

526 Background: High tumor grade is included in practice guidelines as a marker of higher recurrence risk in stage II colon cancer. Multiple systems for tumor grading exist, without a standardized approach. We characterize agreement of 2 methods for tumor grading and association with recurrence in the context of clinical, pathologic, and genomic tumor features including mismatch repair (MMR) and the 12-gene recurrence score (RS). Methods: Colon tumors were graded independently by 2 academic GI pathologists (P1, P2). Grade was defined by % tumor with gland-like structures: well (> 95%), moderately (50-95%) and poorly (< 50%) differentiated. P1 used this 3-tier system while P2 used 2-tier scheme with well and moderately differentiated tumors defined as low grade and poorly differentiated as high grade. All mucinous tumors were high-grade by P2 but not P1. Relationship to recurrence-free interval (RFI) was assessed by Cox regression. Results: Primary tumors from 504 stage II colon cancer treated with surgery alone were included. 18% (P1) and 31% (P2) were high grade. High grade tumors were more likely right-sided (≥ 60%) and MMR deficient (≥ 35%) for P1 and P2 (all p < 0.001). Proportion of mucinous tumors was similar for high and low grade by P1 (25% vs. 21%, p = 0.39). P2 high grade trended to lower recurrence (HR = 0.63, p = 0.10) while P1 grade was not associated w/ RFI (p = 0.46). In multivariate analyses including grade and RS, P2 high grade was associated with lower recurrence (p = 0.007) but P1 grade was not associated w/ RFI (p = 0.30). Neither grade was associated w/ RFI (p > 0.30) after controlling for RS, MMR, tumor location and mucinous histology. Using the two-tier scheme, agreement b/w the 2 pathologists was low (kappa = 0.30, 95% CI 0.21-0.39) in all pts and moderate if mucinous tumors were excluded (kappa = 0.52, 95% CI 0.40-0.64). Conclusions: High tumor grade was not found to be a marker of higher recurrence risk in stage II colon cancer. Other markers validated in stage II colon cancer, such as MMR and RS, should be considered. Interpathologist agreement on colon tumor grade is modest, even with central expert review. [Table: see text]
Helical tomotherapy for anal cancer: Initial clinical outcomes and organ motion.
Authors: Siker M. L. , Qi X. S. , Hu B. , Wong S. J. , Li X. A. , Erickson B. 
Published: February 2017

530 Background: Helical tomotherapy (HT) delivers rotational IMRT with megavoltage CT (MVCT) guidance for patient positioning, offering improved dose conformality and accuracy. We report preliminary clinical outcomes using HT in patients with anal cancer with estimated organ motion and delivered doses. Methods: From 9/2005-8/2009, 15 patients with anal cancer were treated with HT and concurrent chemotherapy (MMC 10 mg/m2 IV bolus d1 and 29; 5FU 1,000 mg/m2/day CI d1-4 and 29-32). Median doses for primary tumor, involved lymph nodes and uninvolved lymph nodes were 50.5, 50.4 and 45 Gy. Dose specifications and target definitions were per RTOG 0529 for the majority. Treatment plans, daily MVCT, and initial clinical outcomes and toxicity were retrospectively analyzed. Center-of-mass (COM) locations and volumes of the targets and OAR with daily shifts were analyzed on selected patients. Doses actually delivered daily were reconstructed. Results: At median follow-up of 15 months, all patients were alive without any evidence of recurrence. There were 40% male, 27% HIV+, 13% T3/4, and 47% lymph node positive. Four patients required treatment break of ≤ 1 week. There were no non-hematologic grade 4/5 toxicities. Overall non-hematologic grade 3 toxicity was 33.3% (GI and skin). All other patients had ≤ grade 2 GI or skin toxicity that completely resolved with aggressive supportive care. There was 40% overall hematologic grade 4 toxicity. Overall hematologic grade 3 toxicity was 60%. Daily shifts were 0.6 ± 3.3, 0.4 ± 3.0, and 0.5 ± 2.2 (SD) mm in lateral, longitudinal and vertical directions. Average daily displacements of the COM from their locations on the planning CT were 9 ± 3, 7 ± 4, 9 ± 2, and 7 ± 2 (SD) mm, for anus, rectum, bladder and vulva. Interfractional organ motion and deformation resulted in variations in the dose delivered in each fraction.For example, daily dose covering 95% of PTV varied by 4%, and vulva volume covered by 50 Gy changed by 23% daily. Conclusions: HT with concurrent chemotherapy is well-tolerated compared to historical reports. Interfractional organ motion is significant and can result in deviations in dose delivery to the target and OAR. Such deviations should be considered in analyzing dose response outcome. No significant financial relationships to disclose.
Long-term follow-up of a multicenter phase II study of chemo-immunotherapy in the treatment of metastatic colorectal cancer (MCC).
Authors: Recchia F. , Candeloro G. , Necozione S. , Lippe P. , Desideri G. , Rea S. 
Published: February 2017

536 Background: The combination of low-dose interleukin-2 (IL-2) and 13-cis retinoic acid (RA) has been shown to decrease vascular endothelial growth factor (VEGF) of patients with MCC (Anticancer Res, 2005). Moreover, results of various studies have shown that the addition of IL-2 and RA to chemotherapy (CT) increased treatment efficacy, inducing a statistically significant decrease of VEGF, with a low cost. Methods: Patients with MCC, deemed unresectable, were given the following treatment for two consecutive days (D1-D2): Oxaliplatin 50 mg/m2, Leucovorin (LV), 200 mg/m2, 5-fluorouracil (5-FU) 400 mg/m2, Capecitabine (C) 2,000 mg/m2 (FOCFOX). After 2 weeks Camptothecin, 90 mg/m2 (D1-D2), was administered with the same doses of LV, 5-FU and C (FOCFIRI) as first-line treatment of MCC. Subcutaneous IL-2 1.8 x 106 I.U. and oral RA, 0.5 mg/kg were given 5 days/week. Induction CT was administered for 12 courses, alternating FOCFOX and FOCFIRI, followed by maintenance treatment with the same schedule of IL-2 + RA, for 3 weeks/month. The primary endpoint was the decrease ≥ 30% of VEGF of patients with MCC. Secondary endpoints were the cost of IL-2 and RA with respect to bevacizumab, toxicity, progression- free survival (PFS), and overall survival (OS). Results: From 08/2000 to 08/2006, fifty-four patients with MCC were entered into the trial. After a median follow up of 64 months (95% CI 62-85%), a statistically significant > 30% (p<0.001) decrease of VEGF was observed. Costs of therapy were $ 304.00/month for IL-2/RA and $ 1,700.00/month for bevacizumab (82% cost reduction). The most common adverse events of CT were grade 3/4 neutropenia, leukopenia, thrombocythopenia, and anemia in 33%, 9%, 2%, and 2% of patients, respectively, peripheral neuropathy in 10% of patients. Mild cutaneous skin rash, fever and autoimmune reactions were observed in the patients who received the maintenance immunotherapy. PFS at 10 months was 76% (95% CI 62-86). Median PFS was 27.8 months, while median OS was 48.8 months. Conclusions: These data show that maintenance immunotherapy with low-dose IL-2 and oral RA in patients with MCC has a low toxicity profile, is cost effective, decrease VEGF and seems to improve expected PFS and OS. No significant financial relationships to disclose.
Survival advantage associated with palliative oophorectomy in patients with metastatic colorectal cancer (CRC) to the ovaries (mCRC-O): A single institution retrospective analysis.
Authors: George B. , You Y. , Viswanathan C. , Wen S. , Baladandayuthapani V. , Overman M. J. , Kee B. K. , Kopetz S. , Eng C. , Garrett C. R. 
Published: February 2017

539 Background: The ovaries are an uncommon site for secondary spread from metastatic CRC. We hypothesize that palliative oophorectomy improves survival among patients with mCRC-O. Methods: We undertook a single institution IRB-approved (DR-09-623) retrospective evaluation of women with mCRC-O from 2001-2008; 110 pts with ovarian metastases and follow-up information for survival analysis were identified out of 3,776 female pts with CRC (2.9%). Survival data was calculated from the date of diagnosis of ovarian metastases (by pathology or radiology) to date of death. Results: Median age of patients was 49 years (range 19-82); median duration of follow-up was 49 months. Twenty patients were identified from 1,758 female patients with CRC seen at our institution from 2001-2004 (1.1%) and ninety patients identified from 2,018 female CRC patients from 2005-2008 (4.5%). KRAS mutation was present in the primary tumor in 23 of 43 (54%). Sixteen evaluable patients who received systemic chemotherapy with mCRC-O and other sites of metastatic disease were identified; five (31%) had a mixed radiographic response (progression in the ovarian metastases with disease response in other sites of metastases). Seventy-one (64.5%) patients had metastatic disease at the time of initial presentation; 39 (35.5%) had completely resected stage II or III CRC with mCRC-O occurring at a later date. 86 (78.2%) underwent unilateral or bilateral oophorectomy for treatment of their disease. Patients who had metastatic disease at presentation and underwent oophorectomy had a median survival of 39.4 months versus 18.2 months for those with ovarian metastases left in situ (p < 0.0001); patients who developed ovarian relapse after prior colectomy and subsequently underwent oophorectomy had a median survival of 50 months versus 12 months for those patients who did not (p = 0.001). Patients with mCRC-O and peritoneal metastases had a significantly worse survival (p = 0.003). Conclusions: This single institution retrospective data analysis suggests that women with colorectal cancer metastatic to the ovaries may derive a survival benefit from palliative oophorectomy. No significant financial relationships to disclose.
Identification of chemosensitivity markers for postoperative adjuvant chemotherapy using cellular, molecular, and immunohistochemical profiles of advanced carcinomas from gastrointestinal tract.
Authors: Nishizuka S. , Ishida K. , Uesugi N. , Matsuo T. , Chiba T. , Ikeda M. , Sugai T. , Otsuka K. , Koeda K. , Wakabayashi G. 
Published: February 2017

55 Background: The prediction of chemotherapeutic efficacy is a fundamental problem. We have developed an effective system to identify prediction markers based on an in vitro approach using a quantitative matrix of chemosensitivity assay (CSA) and protein expression by reverse-phase protein lysate microarrays (RPA), followed by tissue microarrays (TMA). In the present study, we attempted to identify predictive markers by extracting candidate proteins from the “chemosensitivity x protein expression matrix” of 12 cancer cell lines and 12 chemotherapeutic agents, followed by examination using TMA in post-operative adjuvant chemotherapy for advanced gastric and colorectal carcinomas. Methods: The “chemosensitivity x protein expression matrix” was constructed using quantitative data from CSA and RPA. TMA was constructed from parafin-embedded, formalin-fixed surgically removed tissues from 30 gastric and 49 colorectal carcinomas. All subjects had received post-operative adjuvant chemotherapy. Expression and/or localization of candidate marker proteins on TMA were evaluated for the comparison of time to relapse (TTR) between the groups based on the score of each candidate marker protein. Results: TTR was compared in each binary score for a candidate marker that showed a moderate to high correlation coefficient of the “chemosensitivity x protein expression matrix” of 144 combinations. Among these candidate combinations, it was found that the presence/absence of NFkB protein nuclear localization and the TTR of those patients who received 5-FU based adjuvant chemotherapy differed significantly. The three-year relapse rate was 28% in NFkB absent cases, whereas it was 84% in the present cases. Conclusions: We identified NFkB nuclear localization as an effective 5-FU based chemotherapeutic prediction marker in the context of gastrointestinal post-operative adjuvant chemotherapy. The combination of CSA, RPA, and TMA technologies may allow rapid identification of chemotherapeutic prediction markers. No significant financial relationships to disclose.
Self-report of neuropathy from oxaliplatin-based regimens in the treatment of colorectal cancer: With or without bevacizumab.
Authors: Wang X. S. , Eng C. , Fogelman D. R. , Malekifar M. , Liao K. E. , Glover K. Y. , Cleeland C. S. 
Published: February 2017

551 Background: Neuropathy attributed to oxaliplatin-based chemotherapy is a dose limiting factor in the administration of chemotherapy. With premising clinical outomes, bevacizumab (BV) has been added with colorectal cancer (CRC) patients in first line and second- line therapy. Although toxicity been well documented, there is no evidence of the impact of adding BV to oxaliplatin-based chemotherapy on patient's neuropathy development during therapy. Methods: The study enrolled 66 colorectal cancer patients naïve to oxaliplatin or to any microtubule stabilizing agents scheduled for oxaliplatin-based chemotherapy, 29 (44%) of whom also received BV. From first therapy cycle start date, patients rated symptoms weekly during chemotherapy via the M. D. Anderson Symptom Inventory (MDASI), and continued symptom assessment every two weeks for up to 48 weeks. Longitudinal symptom responses were analyzed by mixed-effect modeling which controlled for age, sex, staging, prior diabetes, and total cycles of chemotherapy received. All cases completed at least 2 cycles chemotherapy. Results: A third of the sample was female; 24% were older than 65 years; 59% with stage IV disease. The five most severe symptoms were numbness, fatigue, sleep disturbance, drowsiness, and distress on MDASI symptom items. The severity of patient-reported numbness/tingling, rated on MDASI, increased overtime in following 48 weeks after started therapy (p < 0.0001). Oxaliplatin-based therapy plus BV, compared to no BV in the regimen, resulted a significant lower severity on numbness/tingling during the study period (estimate = -1.1325, p = 0.0005). Older patients reported more numbness/tingling. In contrast, pain severity remained low during the initial cycles of therapy, but significantly increased over time during therapy. Therapy with or without BV did not produce differences in pain development. Conclusions: This prospective study suggests that adding BV to standard oxaliplitin-based therapy for CRC was associated with significantly reduced numbness/tingling development. This observation needs to be confirmed in larger studies. The mechanism(s) by which neuropathy could be attenuated by BV are unknown. No significant financial relationships to disclose.
Phase II study of combination chemotherapy with biweekly cetuximab and irinotecan for wild-type KRAS metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines.
Authors: Yuki S. , Shitara K. , Yoshida M. , Takahari D. , Utsunomiya S. , Yokota T. , Sato Y. , Tajika M. , Muro K. 
Published: February 2017

561 Background: Weekly cetuximab and irinotecan is a standard regimen in heavily pretreated patients with metastatic colorectal cancer (MCRC). The aim of this study was to prospectively evaluate the efficacy of combination chemotherapy with biweekly cetuximab and irinotecan in patients with pretreated MCRC harboring wild-type KRAS. Methods: Patients with wild- type KRAS MCRC that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included in this study. Cetuximab was administered at 500 mg/m2 biweekly with irinotecan. The primary endpoint was response rate. The secondary endpoints included adverse events, progression-free survival, and overall survival. The pharmacokinetics of cetuximab was also evaluated in five patients. Results: From May, 2009 to February, 2010, a total of 31 patients were enrolled from five institutions. One patient was not eligible. Among the 30 assessable patients, ECOG PS was 0 in 12, 1 in 16, and 2 in two patients. The objective response rate was 30.0% (95% confidence interval [CI], 14.7-49.4), and the disease control rate (complete response, partial response, or stable disease) was 76.7% (95%CI, 61.4-92.3). The median progression-free survival was 5.3 months (95%CI, 3.4-7.3). Grade 3 skin toxicity was observed in 3 patients (10%), and treatment related death due to pneumonia occurred in one patient. Conclusions: The efficacy data are similar to those of standard dose of cetuximab plus irinotecan. Combination chemotherapy with biweekly cetuximab and irinotecan is effective for pretreated metastatic wild-type KRAS MCRC. No significant financial relationships to disclose.
Nurse-lead clinics for capecitabine: A prospective audit evaluating changes in toxicity profile and efficacy.
Authors: Samuel L. M. , Lynch D. , Christie G. , Collie J. , McLachlan N. , Jordan J. , Macdonald A. , Gent P. 
Published: February 2017

564 Background: Oral chemotherapy offers patients equal efficacy but fewer visits to hospital and less time spent traveling, but there are concerns about toxicity and compliance. Nursing and physician interactions with patients are different, and when a nurse-lead oral chemotherapy service was developed in NE Scotland in 2003 a prospective audit was begun to monitor safety and efficacy. Methods: Patients with colorectal cancer who declined or were not eligible for appropriate clinical trials had their course of adjuvant or palliative capecitabine chemotherapy prospectively monitored through a nurse-lead clinic. At every clinic visit data was collected on patient demographics, blood and imaging results, and adverse events (AEs). Any decision to change dose was made by the colorectal oncology medical staff. Results: From September 2003 to November 2006 there were 177 patients prospectively monitored through the nurse-lead clinics. Palliative patients (n = 100), median age 69 (range 43-89) and majority PS 0 or 1. Initial dose reduction in 30% due to low GFR and 13% due to being >75 years old. Overall 77% of patients completed on the starting dose. AE's, shown in table, and efficacy compared with capecitabine registration data (younger age group). Median overall survival 47.7 weeks (cf 56.6 weeks). Adjuvant patients (n = 77), median age 64 (range 40-88) and all PS 0 or 1. Initial dose reduction in 19% due to low GFR and 2% due to being >75 years old. Overall 58% completed on the starting dose (= X-ACT study). AEs, other than 5% G3/4 lethargy, and efficacy similar when compared with X-ACT data, including 3 year DFS of 64% (cf X-ACT 64%). Conclusions: Using nurses to assess patients receiving capecitabine does not seem to significantly alter efficacy but does alter the AE profile compared with the registration data, particularly in the palliative patients. Differences in the nurse-patient relationship with nurses seen as less busy, more approachable and not taking treatment decisions can improve the quality of care in patients receiving capecitabine chemotherapy. [Table: see text] [Table: see text]
The role of UGT1A1 polymorphisms (*28 and *6) in Japanese cancer patients.
Authors: Morimoto S. , Shimada M. , Kurita N. , Iwata T. , Nishioka M. , Yoshikawa K. , Miyatani T. , Mikami C. , Kashihara H. 
Published: February 2017

570 Background: Combination protocol using FU-LV with irinotecan (FOLFIRI) is currently regarded as standard first-line therapy in advanced colorectal cancer (CRC). Although irinotecan prolongs survival, it causes severe diarrhea and neutropenia. Recent pharmacogenetic studies on irinotecan have revealed significant associations of UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms *28 and *6, the latter being specifically detected in East Asians resulting in severe toxicity. It is necessary that the dose-finding trial that decided the optimal dose according to the gene polymorphism to draw out the maximum therapeutic effect while evading the side effect. Here we present the result of prospective trial of the safety about FOLFIRI therapy according to each gene type of UGT1A1 for Japanese patients with advanced CRC. Methods: From 2008, 250 Japanese patients in TOKUSHIMA University were enrolled in this study. Homo group (*6/*6 and *28/*28 or a both hetero types), hetero group (It was *28 and either *6 was hetero type), and wild group (*28 and *6 were wild types) were defined. On the 23 patients with advanced CRC treated with FOLFIRI after standard chemotherapy, wild and homo groups were administered 150mg/m2 irinotecan, and homo group was 100mg/m2. Results: On the 23 patients, the genotypes of UGT1A1 *28 were homozygous in 1 (0.5%) and heterozygous in 5 (28%), *6 were homozygous in 0 and heterozygous in 6 (26%). In *6 heterozygous patients, severe toxicities (grade 3 or more) were found (33%), but in *28 heterozygous patients were not (0%). There was no decrease of irinotecan doses in each group. In Japanese people, UGT1A1 *6 polymorphisms were higher than *28 (*6 homo 3%, hetero 27% vs *28 homo 0.5%, hetero 13%). Conclusions: When the dosage of irinotecan is decided, it is necessary to consider the UGT1A1 *6 heterozygous in Japanese cancer patients. [Table: see text]