bluuebunny/crossref_metadata_2025_split huggingface dataset:
Six months compared with 12 months of capecitabine as adjuvant chemotherapy for stage III (Dukes' C) colon cancer: Rationale for the open-label randomized phase III study, JFMC37-0801.
Authors: Takahashi T. , Yoshida K. , Hamada C. , Sakamoto J. , Satoh T. , Sadahiro S. , Mishima H. , Watanabe M. , Sugihara K. , Tomita N. 
Published: February 2017

517 Background: The standard duration of adjuvant chemotherapy (CT) in patient with stage III colorectal cancer is 6 months. On the other hand, no clinical trial which investigate an optimal duration of oral chemotherapeutic agents has yet been implemented for adjuvant treatments. According to the ACCENT database (Sargent, et al. J Clin Oncol 27: 872- 877, 2009), 83% of recurrences in stage II and III pts have occurred within the first 3 years after surgery and peak was observed around one year after surgery. Also, single-agent FU-based adjuvant CT reduced the hazard rate of OS, DFS, and TTR, although the peak of events around one year was still remained especially for stage III pts. We analyzed the data of recurrent risk of curatively resected colon cancer pts provided by JFMC7-1-7-2-15, X-ACT. Surgery alone group and 6 months CT (5FU/LV or capecitabine [Cape]) showed highest peak between 12 months to 18 months after surgery, but 12 months oral 5-FUs group did not show recurrence peak between 12 months to 18 months after surgery. Therefore, to clarify the benefit of 12 month administration of Cape, we planned a phase III randomized trial for a comparison of 6 months treatment and 12 months treatment. Methods: JFMC37 is a multicenter, randomized phase III trial. Patients with fully resected stage III colon or recto sigmoid cancer were eligible. Patients were randomized 1:1 to receive Cape of 6 months (arm A) or Cape of 12 months (arm B). Primary endpoint is disease-free survival. The statistical design is based on superiority hypothesis; 5-yrs DFS is 60% in arm A, 67% in arm B; unilateral α=0.05, 1-β=0.8; and planed accrual is 1200 pts. Results: Between September 2008 to December 2009, 1,304 pts were randomized. Patients characteristics are (armA/armB); number 653/651, gender M352-F301/M343-F308, median age 65 years/65 years, ECOG PS=0-1 620-33/632-19, involvement of lymph nodes=N0-N1-N2 503-130-20/499-128-24. There were no differences in baseline characteristics between arm A and arm B. Conclusions: This trial is expected to show if 1 year adjutant chemotherapy with capecitabine can reduce the peak of recurrence in 1 year and provide long-term OS benefit. [Table: see text]
Racial disparity trends in clinical presentation and outcomes in colorectal cancer: Findings from an urban university hospital.
Authors: Mitchell E. P. , Topham A. , Singla R. , Maron S. , Schoenfeld J. , Guiles F. , Goldstein S. , Anne P. R. , Isenberg G. , Maxwell P. J. 
Published: February 2017

518 Background: African Americans (AA) have a higher incidence and lower survival rates from colon and rectal cancer than Caucasian Americans (C). This disparity has been attributed to many factors, including diagnosis at later stage, unfavorable histopathologic features, inadequate treatment, and socioeconomic factors. The multidisciplinary management setting ensures similarity in management and treatment planning. In this study, we assessed the pathological features and evaluated survival outcomes in patients with CRC in AA and CA using a large single institutional database. Methods: We compiled data from 3,826 patients with colon and rectal cancer treated at Thomas Jefferson University Hospital from 1988-2009 and used Surveillance Epidemiology and End Results registry data from 1988-2004 to compare survival rates. Independent variables included age, racial background, site of primary tumor, degree of differentiation, stage at presentation, recurrence-free survival and overall survival rates for colon and rectal cancer and for each stage of disease. We compared survival rates using statistical modeling to account for differences in patient and disease characteristics between the two groups. Results: At diagnosis, AA pts presented with more advanced stage of disease (p < 0.0001), were more likely to have proximal disease (p < 0.000000528), had worse overall 5-year survival, and worse survival stage-by-stage than C patients. Data also showed that the odds ratio for risk of nodal involvement was greater for AA pts than C pts with lower T tumors. AA pts were more likely to have less well differentiated colon tumors, but more well differentiated rectal tumors, younger age and worse survival stage-by stage than C pts. Although C pts were more likely to have rectal cancer (p < 0.0001), they were less likely to have stage IV disease at presentation. Conclusions: AA pts with CRC are more likely to present at a younger age with later stage, more proximal tumors, have higher nodal involvement with lower T lesions, and less well differentiated tumors than C. Additional studies on biological feature sand molecular markers are ongoing to and will be presented. No significant financial relationships to disclose.
Rapid 5-fluorouracil plasma quantification by immunoassay: Validation with FOLFOX6 clinical samples.
Authors: Salamone S. J. , Benfield C. N. , Courtney J. B. , Harney R. L. , Kozo D. R. , Li Y. , Lundell G. D. 
Published: February 2017

563 Background: 5-fluorouracil (5-FU) is one of the most widely used chemotherapy agents in the treatment of colorectal cancer. Studies over the last 30 years have demonstrated wide pharmacokinetic variability of 5-FU which can lead to undue toxicity and suboptimal treatment. Recent clinical studies have demonstrated that managing plasma 5-FU levels and adjusting doses to target steady state concentrations effectively minimizes toxicity and improves outcome. Methods: An existing immunoassay using a novel antibody to 5-FU was modified to directly quantify 5-FU in patient plasma samples without any sample pretreatment. The assay was adapted to Beckman Coulter AU analyzers and to Roche COBAS c 111 analyzer. Method comparison to LC-MS/MS, limit of detection (LoD), lower limit of quantitation (LLoQ), precision, and linearity of the assay were evaluated. The assay was also validated by testing samples of patients being treated by modified FOLFOX6 from an on-going clinical trial ( NCT00943137 ). Results: The modified immunoassay was confirmed to have a linear reportable range from 85 to 18,000ng/mL and a LoD of 52ng/mL. The immunoassay was established to have good precision (CV<6%) around the medical decision points for FOLFOX and FOLFIRI regimens. Method comparison of the immunoassay obtained by testing 58 clinical samples from patients under 5-FU treatment provides excellent correlation to LC- MS/MS: Deming slope 1 ± 0.05, R > 0.98. Another 82 samples of patients on modified FOLFOX6 regimen from clinical trial (( NCT00943137 ) were tested using the immunoassay and range of these sample were reported to be from 95 to 2,970 ng/mL. Conclusions: The assay provided the performance required to rapidly quantify 5-FU plasma concentrations. It was fast (time to 1st result < 10 minutes), precise, correlated well to a physical method, required only 100uL sample on the analyzer and 7ul for actual testing per assay, and was easily adapted to a variety of clinical analyzers. Clinical and pharmacokinetic laboratories could use this assay to introduce an evidence-based approach to optimize 5-FU dosing that would have higher throughput, simpler methodology, and require less labor, space or expense than the physical methods. [Table: see text]
Incidence of FOLFOX induced amenorrhea in women age 40 and younger with colorectal cancer.
Authors: Cercek A. , Reidy D. L. , Saltz L. 
Published: February 2017

567 Background: The effects of oxaliplatin-based chemotherapy on female fertility are largely unknown. Studies have indicated that the incidence of young women diagnosed with colorectal cancer is on the rise, thus there is an increasing number of female colorectal cancer survivors of child-bearing age. Adjuvant FOLFOX chemotherapy is the most widely used standard treatment for stage III and high- risk stage II colon cancer. The objective of this analysis was to evaluate the incidence of amenorrhea as a crude measure of potential fertility in women age 40 and younger treated with FOLFOX. Methods: A search of computerized pharmacy records identified 45 women age 40 or younger who received adjuvant FOLFOX chemotherapy at Memorial Sloan-Kettering for stage II or III colorectal cancer from January 2002 and January 2009. Fourteen patient s had received pelvic radiation and 3 developed metastatic disease and were thus ineligible. A total of 28 patients were eligible and were mailed an anonymous questionnaire asking their age at time of diagnosis and specific questions regarding their menses pre-, during, and post-chemotherapy. The returned surveys were reviewed and the results tallied. Results: Of the 28 patients that met the eligibility criteria and were mailed the survey 16 (57%) returned the questionnaire. One patient had undergone bilateral oophorectomy and was ineligible. The majority of patients were 31-35 years old (range 21-40). All but one patient had regular pretreatment menses. Of the 15 eligible patients, 7 maintained their usual menses throughout chemo, 3 noted a change in their menses, and 6 lost their cycles. Only 1 (6%) did not regain her menstrual cycle 6 months after stopping chemotherapy. Conclusions: In this small retrospective study, the incidence of amenorrhea in young women treated with FOLFOX chemotherapy is quite low. Prospective studies are planned to more accurately characterize the impact of FOLFOX on female fertility. [Table: see text]
Bidirectional intraperitoneal chemotherapy with oxaliplatin in the context of CRS and HIPEC in patients with peritoneal carcinomatosis.
Authors: Glockzin G. , Schlitt H. J. , Piso P. 
Published: February 2017

568 Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provide a promising therapeutic option for selected patients with peritoneal carcinomatosis. The use of oxaliplatin as an intraperitoneal cytostatic agent seems to further improve the efficacy of the combined treatment concept. Nevertheless, additional toxicity in comparison to mitomycin C and/or doxorubicin might be exspected. Methods: Between 02/2008 and 08/2010 40 patients underwent CRS and HIPEC with oxaliplatin at a concentration of 300 mg/sqm at the University Medical Center Regensburg. Thirty-five of these patients received bidirectional chemotherapy with additional intravenous application of 5FU/LV and 5 patients intraperitoneal oxaliplatin only. Perfusion time was 30 and 60 minutes, respectively. A matched-pair analysis was performed to compare IP oxaliplatin to our former standard HIPEC with mitomycin C and doxorubicin. Matching criteria were operating time, age and sex. Results: The mean operating time in the OX and the MMC group was 315 and 313 minutes, respectively. The mean age was 52 and 51 years, and 15 versus 16 patients were female, respectively. Median hospital stay was 15.5 days in the OX group and 17 days in the MMC group. The median stay on ICU was one day in both groups. The grade 3/4 morbidity rate was 42.5 % versus 37.5 % (p = 0.648). Five versus six patients had to be reoperated. Perioperative morbidity was 2.5 % versus 0 %. Main complications in the OX group were pleural effusion (5), thrombosis (2), cardiac arrhythmia (2), and abscess (2). In the MMC group postoperative morbidity was mainly caused by ileus (4), anastomotic leakage (3), pulmonary embolism (2), and wound infection (2). Conclusions: Our data suggest that the use of IP oxaliplatin in the context of CRS and HIPEC does not increase perioperative morbidity and/or mortality rate. Nevertheless, randomized controlled trials are required to determine the best intraperitoneal chemotherapeutic regimen regarding toxicity and oncological outcome. No significant financial relationships to disclose.
Role of thrombospondin 1 (THBS1) expression in peritoneal metastasis of gastric cancer treated with taxanes.
Authors: Kurita N. , Shimada M. , Iwata T. , Nishioka M. , Morimoto S. , Yoshikawa K. , Miyatani T. , Mikami C. , Kashihara H. 
Published: February 2017

57 Background: To clarify the utility of taxanes and to pick up the prognostic factors in the treatment with 5FU- based chemotherapy for peritoneal metastasis of gastric cancer. Methods: Responder analysis: 18 patients with peritoneal metastasis of gastric cancer were enrolled in phase I study. The regimen consists of S-1 (80-120 mg) for 14 days and intraperitoneal infusion of PTX (dose escalation: 40 - 100 mg/m2) at day 1 and 14, which was repeated 2 cycles. To pick up the predictive factors, the 137 genes, which were selected in the viewpoint of sensitivity of 5FU, CPT11 and taxanes, were analyzed using focused DNA microarray for the 12 patients. Role of THBS1 expression: THBS1 expressions were evaluated in immunohistochemical (IHC) staining of surgical specimens of 59 patients with peritoneal metastasis of gastric cancer who were administered 5FU-based chemotherapy. THBS1 positive was defined > 30% of the population stained moderate to strong. Results: Responder analysis: Expressions of THBS1 gene of the 6 patients who had clinical benefits (2: partial response, 2: positive adenocarcinoma cells in peritoneal cytology became negative, 2: remarkable decrease of ascites) were more than 2 folds higher than those of no responders. THBS1 expression was confirmed in 5 (83.3%) using IHC staining, who had significantly higher survival rate compared with that of the negative. Role of THBS1 expression: 17 patients (28.8%) was THBS1 positive and had significantly better prognosis compared with negative patients (1year survival: 64.7% vs 34.7%). 38 patients treated with regimes including taxanes revealed a tendency of improved overall survival rates (p=0.05). Overall survival of 15 patients with THBS1 positive administered taxanes was significantly higher than that of the negative patients. (1 year survival: 66.7% vs 42.4%) Conclusions: PTX could improve the survival of peritoneal metastasis of gastric cancer. THBS1 is a prognostic factor especially in the patients treated with taxanes, which leads to tailor-made therapy. [Table: see text]
Phase II trial of cetuximab plus irinotecan for FOLFOX and FOLFIRI-refractory patients with EGFR-positive advanced and/or metastatic colorectal cancer: Evaluation of the efficacy and safety based on KRAS mutation status (T- CORE0801).
Authors: Shimodaira H. , Soeda H. , Gamoh M. , Andoh H. , Yamaguchi T. , Watanabe M. , Isobe H. , Sudo T. , Kato S. , Ishioka C. ,   T-CORE
Published: February 2017

573 Background: Activating mutation of the KRAS gene is a predictive biomarker for loss of efficacy to anti-EGFR antibody therapy. However, this was mainly established by the evidences of Caucasian studies. Then, this prospective study investigated the role of KRAS mutations on efficacy and safety to cetuximab plus irinotecan in Japanese patients with metastatic colorectal cancer (mCRC). Methods: We conducted a prospective study to analyze objective response to cetuximab plus irinotecan in molecularly defined KRAS wild-type (WT) or mutant subgroups of chemotherapy-refractory mCRC. KRAS mutations were detected by direct sequence on DNA from formalin-fixed, paraffin-embedded tissue of patients treated in 11 centers in Japan. Additional EGFR related genes such as BRAF, PIK3CA etc. and antibody-dependent cellular cytotoxicity related polymorphism in FCγRIIa and RIIIa genes were also examined. Results: Forty-three patients were enrolled. KRAS mutations were found in 31.7% of 41 eligible patients. Response rate (RR) to cetuximab plus irinotecan, the primary endpoint of the study, was 17.9% and 0% for the patients with tumor harboring WT and mutant KRAS, respectively. No significant differences in toxicity were observed between the KRAS WT and mutant groups. Detail statistical analyses are ongoing. Conclusions: We confirmed that KRAS status is a useful predictive maker for the efficacy to cetuximab plus irinotecan therapy in Japanese mCRC patients, even though the response rate in the KRAS WT group was lower than expected. [Table: see text]
Primary colon cancer site as a predictor of bevacizumab effectiveness in metastatic colon cancer patients.
Authors: Islam R. , Chyou P. , Ege H. , Deedon A. , Burmester J. K. 
Published: February 2017

574 Background: Bevacizumab has been approved by the FDA for first-line treatment in combination with chemotherapy for metastatic colon cancer. Although bevacizumab extends progression free survival and overall survival for many metastatic colon cancer patients, primary cancer site has not been examined as a predictor of its effectiveness. Methods: Data regarding bevacizumab treatment for colorectal cancer were abstracted from the medical record of 175 patients treated at a large multi-specialty clinic. Data were collected regarding demographics, body mass index, weight loss, lifestyle variables (smoking status, drinking habit), history of colon polyps, family history of cancer, primary site of tumor in the colon, tumor stage, lymph node involvement, metastasis, tumor grade of metastasis, cancer cell type, symptoms related to the cancer, and other comorbidities (cardiovascular disease, diabetes mellitus, Crohn's disease, diverticulitis, and irritable bowel syndrome).Tumor response was measured by radiologic and biochemical markers. Univariate and multivariate analyses were performed using Fisher's exact test, Wilconox rank sum test, and unconditional logistic regression modeling. Results: Univariate analysis demonstrated that positive tumor response was positively correlated with blood in stool (p=0.0301), advanced lymph node stage (p=0.048), and adenocarcinoma cancer cell type (p=0.0387), but negatively correlated with chemotherapy treatment of the primary tumor (p=0.0387) and primary site of the colon cancer (p=0.0328). Multivariate stepwise logistic regression analysis demonstrated that patients with primary tumor located in the transverse or descending/sigmoid colon were more likely (odds ratio=5.88, 95% confidence interval: 1.72–20.00; p=0.0046) to have a positive tumor response than patients whose primary tumor site was cecal/ascending colon. Conclusions: Primary site of metastatic colon cancer may influence the effectiveness of bevacizumab therapy. Future randomized, controlled trials are needed to examine the primary site as a predictor of tumor response in metastatic colon cancer patients using bevacizumab therapy. No significant financial relationships to disclose.
Colorectal cancer in elderly patients: A single-center experience.
Authors: Resch G. , Poetscher M. , Schauer W. , Hoebling W. , Mayrbaeurl B. , Burgstaller S. , Thaler J. 
Published: February 2017

576 Background: In Austria more than 40% of cancers occur in adults over the age of 75 years. As the current population ages and more people live longer, the incidence of cancer in elderly patients (pts) is expected to rise. Several studies have shown that cancer treatment is beneficial for elderly pts in adjuvant and palliative setting. However, elderly pts with cancer have been underrepresented in clinical trials and there is little literature on this pts group. We now want to present our own experience in the treatment of elderly pts with colorectal cancer (CRC). Methods: Since July 2006 all pts with new diagnosed CRC were recorded in a tumor registry at the Klinikum Wels- Grieskirchen. Patients were followed for treatment decision, progression free survival and overall survival. In this retrospective analysis elderly pts >75 years diagnosed with CRC have been evaluated. Results: Overall, 165 pts >75 years (range 75-92) with a diagnosis of CRC stage I-IV were recorded from July 2006-July 2010 in our registry. Seventy-six (46.1%) and 89 (53.9%) out of these pts were men and women. Stage I has been diagnosed in 25 pts (15.2%), stage II in 57 pts (34.5%), stage III in 47 pts (28.5%) and stage IV in 36 pts (21.8%). 30.7 % (51 pts) had a tumor located in the rectum and 69.3% had colon cancer. 154 out of 165 pts underwent surgery (tumorectomy or colectomy). In one patient with stage II and in 11 pts with stage IV surgery was not possible because of poor performance status. Adjuvant chemotherapy was given in 8 pts with stage II and in 25/47 pts with stage III CRC. 11/36 pts were treated with palliative chemotherapy in stage IV CRC. 17 pts with stage I-III develop distant metastases and 11 out of these pts have been treated with palliative chemotherapy. Hemihepatectomy and lobectomy has been performed in 7 and 1 pts. Overall 13 pts (7.9%) were treated within a clinical trial for CRC. Chemotherapy regimens, progression free survival and overall survival data will be presented. Conclusions: Although elderly pts often have comorbidities and poor performance status, age alone should not determine treatment options and person's eligibility in clinical trials. A careful discussion of treatment risks and benefits, especially in elderly pts, needs to be considered in the therapy decision. No significant financial relationships to disclose.
Outcomes of definitive chemoradiation for squamous cell carcinoma of the anus and the effect of radiation technique on hematologic parameters.
Authors: Novak C. J. , Golden D. W. , Liauw S. L. 
Published: February 2017

580 Background: Chemotherapy-radiation (CRT) is an established therapy for squamous cell carcinoma of the anus. A limiting factor in the successful completion of CRT is bone marrow toxicity. The effect of intensity modulated radiation therapy (IMRT) on marrow toxicity is not well defined. We evaluated the effect of IMRT on the severity of cytopenias for patients receiving CRT. We also explored the influence of cytopenias on disease outcome both pre-CRT or during CRT. Methods: 43 patients were treated with CRT between 1994-2010. The median delivered dose was 50.4 Gy (range, 32.4-59.4). 31 patients (72%) were treated with IMRT. All patients received concurrent chemotherapy, usually 5FU and mitomycin-C (n = 34, 79%). White blood cell (WBC), hemoglobin (Hg), and platelet counts were recorded pre- CRT, weekly during CRT, and within 7 days post-CRT. Hematologic values were analyzed according to type of RT and for association with treatment outcome. Results: 2-year locoregional failure (LRF) and distant failure were 14% and 14%, respectively. 21 patients required a treatment break due to any cause. In 9 (43%) patients the break was due to hematologic toxicity. 34 patients had complete blood values available. IMRT did not affect the rate of ≥ grade 2 cytopenia (p = 0.64) or median treatment nadirs; Hg (9.1 vs. 8.3 g/dL, p = 0.24), WBC (1.7 vs. 1.2 K/uL, p = 0.95), or platelets (90.5 vs. 61.5 k/uL, p = 0.88). Median time to nadir was not different for WBC (7 vs. 7 days, p = 0.36) or Hg (36 vs. 22 days, p = 0.29), but patients treated with IMRT did have a delayed platelet nadir (33 vs. 14 days, p = 0.01). Hg nadir ≤ 9 g/dL was associated with a higher rate of 2- year LRF (> 9 g/dL 100% vs. ≤ 9 g/dL 73%, p = 0.03). No other hematologic values were associated with LRF. Conclusions: In this cohort of patients, nearly 50% of patients required a treatment break, which was related to a cytopenia 43% of the time. IMRT did not appear to have significant impact on acute marrow toxicity, although sample size may limit our power to detect a difference. Low Hg during CRT appears to influence LRF. More detailed dose volume histogram analysis will be useful to further explore how IMRT might influence acute hematologic toxicity, and therefore treatment outcomes. No significant financial relationships to disclose.