bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of adjuvant therapy for treatment of stage II colon cancer in patients with diabetes.
Authors: Dinh T. , Alperin P. , O'Neil B. H. 
Published: February 2017

421 Background: The decision to treat stage II colon cancer patients with adjuvant chemotherapy involves assessment of life expectancy, risk for recurrent disease, and the potential benefit and likelihood of adverse effects from treatment. This is a challenging task, particularly for patients with pre-existing chronic illnesses such as diabetes, which may increase side effects and potentially lessen response to chemotherapy. Methods: We use the Archimedes Model to analyze cost effectiveness of adjuvant therapy in stage II colon cancer patients with pre-existing diabetes. The Archimedes Model is a large-scale, integrated mathematical model of human physiology, diseases, and healthcare systems, including pathways relating to diabetes, cardiovascular disease, and cancers of the breast, lung, and colon. The colon cancer model is built using the SEER, ACCENT databases and meta-analyses of clinical trials. Costs relating to colon cancer, diabetes and its complications are based on Medicare reimbursement rates. We simulate a trial in which stage II colon cancer patients are subjected to two treatment strategies: no treatment vs. adjuvant chemotherapy by FOLFOX regimen. We report incremental cost-effectiveness ratio (ICER), measured by cost per quality-adjusted life year (QALY) gained, of adjuvant therapy compared with no treatment. Results: Cost effectiveness is strongly dependent on a patient's tumor profile, age and duration of diabetes. For instance, adjuvant therapy saves ∼0.2 QALYs per person in stage IIA patients who are 75 and older and have been diagnosed with diabetes >10 years, at an ICER of >$150,000/QALY gained. In contrast, it saves 1.1 QALYs per person in stage IIB patients aged 60-65, recently diagnosed with diabetes, at an ICER of <$30,000/QALY gained. Results are sensitive to assumptions on efficacy and side effects of chemotherapy in diabetic patients, as well as cost of adjuvant therapy. Conclusions: The current study suggests that the decision to proceed with adjuvant chemotherapy requires careful assessment of severity of diabetes in stage II colon cancer patients with pre-existing diabetes. No significant financial relationships to disclose.
Biomarker study in rectal cancer patients after 5FU-based radiochemotherapy: Evaluation of the prognostic capacity of thymidylate synthase in pretreatment biopsies and resected adenocarcinoma.
Authors: Conradi L. , Bleckmann A. , Schirmer M. , Sprenger T. , Homayounfar K. , Wolff H. A. , Becker H. , Ghadimi B. M. , Beissbarth T. , Liersch T. 
Published: February 2017

435 Background: Fluorouracil (5FU) remains the backbone of neoadjuvant radiochemotherapy (RCT) as well as adjuvant therapeutic strategies in multimodal treatment of rectal cancer patients. Due to its central role as the major target of 5FU thymidylate synthase (TS) is a promising biomarker in rectal cancer. We assessed TS in 208 patients with regard to its predictive/prognostic capacity for disease free DFS and overall cancer specific survival (CSS). Methods: 167 patients cUICC stages II (28%) and III (72%) received preoperative 5FU based RCT followed by total mesorectal excision (TME) A comparison group n = 41 received postoperative RCT after primary TME. All patients were treated after standardized protocols within phase-II/-III trials of the German Rectal Cancer Study Group. TS levels from pretreatment biopsies and corresponding resection specimens were assessed by immunohistochemical staining for their impact on DFS and CSS. Additionally, a TS gene polymorphism (28 bp repeat) was analysed in respect to intracellular protein expression levels and prognostic significance. Results: Patients with low TS expression in pre-treatment biopsies showed a correlation with impaired CSS (p = 0.015). After neoadjuvant RCT there was evidence of lymph node metastases ypUICC stage III in 32.6%. Complete histopathologically confirmed tumor regression TRG 4 was achieved in 16 patients (9.5%). During follow-up (median 57 months) patients with low intratumoral TS expression and positive nodal status were at high risk for local and/or distant metastatic recurrence (p = 0.040). Analysis of the 28bp repeat revealed a correlation of *3/*3 genotype with high TS expression in pretherapeutical biopsies (p = 0.05). Conclusions: TS represents a prognostic biomarker in locally advanced rectal cancer indicating an unfavourable outcome for patients with low TS expression and might help to adapt adjuvant therapy regimens by stratifying patients according to their risk for cancer recurrence. No significant financial relationships to disclose.
Ten fractions of preoperative radiotherapy for advanced rectal cancer: Is it a new protocol to follow?
Authors: Gu J. 
Published: February 2017

439 Background: This study is a retrospective analysis to investigate the efficiency of short-course preoperative radiotherapy following standardized total mesorectal excision (TME) for locally advanced rectal cancer. Methods: Clinical data of locally advanced mid-low rectal cancer who received TME in Beijing Cancer Hospital from 2001 to 2005 were collected retrospectively. Survival analysis was performed between patients who had TME following short-course preoperative radiotherapy (biological equivalent dose: 36Gy) or TME alone at the corresponding period. Results: Two hundred and sixty-three patients were eligible for analysis including 101 patients who received TME plus preoperative radiotherapy (PRT group) and 162 patients with TME alone (TME group). The occurrence of TNM downstaging in PRT group was 49.5%, including five percent who had complete response. The local reccurence rate was 4% in PRT group and 8.4% in TME group, with statistically different (p=0.04). An significant improved 5-year overall survival and disease-free survival was obtained in PRT group comparing with TME group (77.2% vs. 69.8%, p=0.04; 76.2% vs. 67.3%, p=0.03). Conclusions: Improved local control and survival benefits could be achieved by short-course preoperative radiotherapy on the basis of standardized TME for locally advanced rectal cancer. No significant financial relationships to disclose.
The optimum number of retrieved lymph nodes for locally advanced rectal cancer following short-course preoperative radiotherapy: A study by fat clearance.
Authors: Gu J. , Wang L. 
Published: February 2017

449 Background: The optimum number of retrieved lymph nodes following preoperative radiotherapy and surgery for locally advanced rectal cancer is still controversial. This study is designed to confirm the least number of retrieved lymph nodes for locally advanced rectal cancer following 30Gy/10f short-course preoperative radiotherapy. Methods: From Aug 2002 to Mar 2010, two hundred and twelve patients with locally advanced rectal cancer received 30Gy/10f preoperative radiotherapy (BED: 36Gy), standardized total mesorectal excision and fat-clearance based pathological evaluation in Beijing Cancer Hospital. The size of retrieved lymph nodes (LNs) was recorded. The sequence of LNs was arranged by a descending sort by retrieved nodes' size and the serial number of the largest metastatic lymph node (mLN) was recorded. The serial number of the first largest mLN is regarded as the least number of LNs to distinguish ypN+ status. The cumulative accuracy of ypN stage by variable numbers of LNs was calculated and analyzed. Results: There were total 4,669 retrieved LNs and 354 mLNs. The median retrieved LNs number was 21 (range 4-61). The ypN positive rate was 40.6%. The peak-value of quantitive distribution of LNs and mLNs was observed in 1-2mm and 3-4mm level. The incidence of retrieving mLNs shows an intensifying tendency for increasing size of LNs. The analysis for sequence of LNs sorting suggested that 85.4% of cases could confirm their ypN stage by the first largest LN. The cumulative accuracy ascended to 95.1% or 98.1% when the first 5 or 9 largest LNs were retrieved. Conclusions: For rectal cancer following 30Gy/10f preoperative radiotherapy, retrieving 12 or more lymph nodes seems not to be mandatory for confirming ypN stage. The accuracy in confirming negative ypN stage when retrieving 5 or 9 largest nodes is sufficient for majority of patients. In those cases that could not retrieve 5 or more nodes by routine fixation, fat clearance is indispensable. No significant financial relationships to disclose.
Frequency of UGT1A1*28 gene polymorphism in Chinese gastrointestinal cancer patients and its relationship with irinotecan-related diarrhea.
Authors: Su Y. , Ma T. , Ye Z. b. , Zhang J. , Zhu Z. G. 
Published: February 2017

451 Background: The incidence of irinotecan-related adverse events was associated with the polymorphism of uridine diphosphate glucuronosyltransferases (UGTs) gene, and demonstrated as obvious ethnic diversity. The aim of this study is to observe the frequency and severity of various adverse events in Han patients with advanced gastrointestinal cancer who was treated with irinotecan-based therapy. Simultaneously, the relationship between the severe adverse events and UGT1A1 gene promoter polymorphism (UGT1A1*28) was investigated. Methods: A total of 109 patients (65 men and 44 women; median 57 years; range: 34-76 years) with advanced gastrointestinal carcinoma receiving irinotecan-based chemotherapy were enrolled. The adverse events during the course chemotherapy, the pretreatment serum bilirubin level, as well as the time to the Grade 3-4 toxicities occurrence were recorded. Genomic DNA was extracted from the peripheral blood to detect the polymorphism of UGT1A1*28 (TATA box thymine-adenine TA repeats). The relationship between the severity of adverse events and UGT1A1*28 polymorphism was investigated. Results: Of all these 109 enrolled patients, 90 patients were identified with thymine-adenine (TA)6/(TA)6 genotype, 19 patients with the thymine-adenine (TA)6/(TA)7 genotype, and no (TA)7/(TA)7 genotype was found. Forty-six and 12 patients developed grade 3-4 neutropenia, while 8 and 5 patients occurred grade 3-4 diarrhea in (TA)6/(TA)6group and (TA)6/(TA)7 group, respectively. The occurrence of grade 3-4 diarrhea but not neutropenia was closely related with (TA)6/(TA)7 genotype in UGT1A1 promoter region in patients receiving irinotecan-based chemotherapy (P=0.033). Conclusions: The frequency of UGT1A1*28 gene polymorphism in Han patients is 17.4%, which is lower than that reported in western populations. The marked increase in grade 3-4 diarrhea is related with (TA)6/(TA)7 genotype of UGT1A1 in patients receiving irinotecan-based chemotherapy. [Table: see text]
Effect of a gene expression-based tissue of origin test's impact on patient management for difficult-to-diagnose primary cancers.
Authors: Hornberger J. C. , Amin M. , Varadhachary G. R. , Henner W. D. , Nystrom J. S. 
Published: February 2017

459 Background: An important step for a novel test is assessing its clinical utility and real-world effect on diagnosis and patient management. This report describes the results of a survey of physicians who have ordered a gene expression profile assay for identification of tumor tissue of origin (Pathwork Tissue of Origin Test) for patients with difficult-to-diagnose primary cancers. Methods: The IRB-approved registry collects data from participating physicians who have ordered the Tissue of Origin test for their patients. To minimize recall bias, a detailed interview is conducted using both a web-based questionnaire and a confirmatory telephone interview with the physicians. Chart survey includes collection of data on patient demographics, diagnostic procedures including imaging and pathology including immunohistochemistry as well as therapy. The physicians are queried regarding their working diagnoses and treatment recommendations prior to and after Tissue of Origin Test result availability. Results: Enrollment in the registry is ongoing. Fifty-nine patients (34 women) have been studied and 48 participating physicians have completed the interview. Survey results suggest that most patients have undergone extensive evaluation including multiple imaging tests (median, 6) and exhaustive immunohistochemistry (median, 10) prior to gene expression analysis. For these 59 pts, based on clinicopathologic evaluation, physicians reported working diagnoses for 46% of patients prior to test results and 83% after test results. Treatment recommendations were changed for 53% of patients. The majority (70%) of treatment changes were for chemotherapy. Physicians (n=26) reported that the Tissue of Origin test decreased the diagnosis associated anxiety in 62% of patients. Conclusions: This ongoing registry study confirms that in patients with difficult-to-diagnose primary cancers, extensive baseline diagnostics is not uncommon and less than half of the patients have an established working diagnosis. Survey results suggest that the Tissue of Origin Test led to a change in working diagnosis and changed treatment recommendations in over half the patients. [Table: see text]
Effect of platelet inhibition on the risk of development of metastatic disease in colorectal cancer.
Authors: Pulte D. , Chalasani S. B. , Bryan M. , Pliner L. F. 
Published: February 2017

470 Background: Platelet inhibition has been shown to decrease the risk of metastatic disease in numerous animal models. The use of aspirin to decrease the risk of colorectal cancer (CRC) has been documented in several large studies. However, to date, no studies of whether the use of aspirin or other platelet inhibiting agent (PIA) will reduce the risk of recurrence in patients who develop CRC have been performed. Methods: In this study, we reviewed the charts of all patients treated at the University of Medicine and Dentistry of New Jersey at Newark for stage II or III colon or rectal cancer. Data extracted included use of PIA, stage, treatment, recurrence, time of last contact, and patient characteristics. Patients were defined as having taken a PIA if any evidence of use could be documented. Statistical significance of differences observed was determined using a Fisher's exact test. Results: 111 charts were initially identified. Use of PIA could not be determined for 6, six had metastatic disease at presentation, and one was stage I, leaving 98 patients for analysis. Of these, 35 had evidence of having used PIA, including 20 patients who were taking aspirin. Forty patients without history of use of a PIA had no metastatic disease, compared to 23 patients who developed metastatic disease. For patients taking PIA, 6 developed metastatic disease (Table). Conclusions: Our results suggest that PIA may help decrease the likelihood of the development of metastatic disease in patients who are diagnosed with stage II or III CRC. The study was limited by the number of patients available, which was not large enough to allow consideration of all possible confounders. Further study of the effects of PIA in a translational and clinical setting including a larger, prospective trial of PIA in stage II/III CRC may lead to further insight into this question. [Table: see text] No significant financial relationships to disclose.
Outcome according to metastatic site in patients with KRAS wild-type tumors: Analysis from the CRYSTAL and OPUS studies.
Authors: Van Cutsem E. , Bokemeyer C. , Heeger S. , Sartorius U. , Rougier P. , Kohne C. 
Published: February 2017

472 Background: The randomized CRYSTAL and OPUS studies showed that adding cetuximab (cet) to first-line chemotherapy (CT) significantly improved clinical benefit in patients (pts) with KRAS wild-type (wt) metastatic colorectal cancer (mCRC). R0 resection of colorectal liver metastases is a potentially curative option in this setting. In this descriptive analysis of these trials the benefit of adding cet to CT according to metastatic site was investigated. Methods: KRAS wt pts were grouped according to liver-limited disease (LLD) and those with other metastatic sites (non-LLD). Treatment arms were compared for response rates (RR), R0 resection rates (R0R), progression-free (PFS) and overall survival (OS). Results: The proportion of patients with LLD was comparable in each study and treatment arm (21%-30%). For most efficacy endpoints, pts with LLD derived greater benefit from CT alone or cet + CT compared with pts with non-LLD (Table). The highest R0R were seen in pts with LLD receiving cet + CT; increasing 2.3 and 3.7 fold from CT alone in the CRYSTAL and OPUS studies respectively. In pts with non-LLD adding cet to CT increased median OS by 5.1 and 3.4 months in the CRYSTAL and OPUS studies respectively (Table). Conclusions: The addition of cet to standard CT increases the R0R, RR, PFS and prolongs OS in first-line mCRC in KRAS wt pts, regardless of LLD. In pts with non- LLD treated with cet and FOLFIRI median OS was prolonged by more than 5 months. [Table: see text] [Table: see text]
Axitinib or bevacizumab (bev) plus FOLFOX or FOLFIRI as second-line therapy in patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Bendell J. C. , Tournigand C. , Bednarczyk M. , Swieboda-Sadlej A. , Chung I. , Barone C. , Tarazi J. C. , Rosbrook B. , Ricart A. D. , Sobrero A. F. 
Published: February 2017

478 Background: Axitinib (AG-013736,AG), an oral selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3, shows activity in multiple tumor types including those refractory to front-line chemotherapy. Methods: This multicenter, open-label, randomized phase II trial compared AG and bev in combination with FOLFOX or FOLFIRI in second-line mCRC. Pts previously treated with irinotecan were randomized to mFOLFOX6 plus AG 5 mg BID or bev 5 mg/kg q2wk; pts who received oxaliplatin were randomized to FOLFIRI with AG or bev at the same doses, with stratification by performance status and prior bev therapy. Primary endpoint was progression-free survival (PFS). Results: 171 pts were randomized from March 2008 to July 2009. There were no significant differences in PFS or median overall survival (mOS) between the AG and bev arms with FOLFOX or FOLFIRI. However, there was a trend towards reduced mOS in the FOLFIRI arms with AG compared to bev, and a trend towards improved mOS with AG+FOLFOX vs bev+FOLFOX. There were more treatment discontinuations (DCs) and a higher incidence of grade ≥3 adverse events (AEs) in the AG arms (diarrhea, asthenia, fatigue; Table). Conclusions: This study did not meet the primary endpoint, showing similar PFS with AG compared to bev when added to second-line chemotherapy. A potential factor in these results was earlier DCs in the AG versus bev arms, likely secondary to increased AEs. While VEGF inhibitors may have a role in second-line treatment of mCRC, at current dosing regimens AG-based chemotherapy shows no improvement in outcome compared to bev. [Table: see text] [Table: see text]
Cetuximab weekly (q1w) versus every two weeks (q2w) plus FOLFOX4 as first-line therapy in patients (pts) with KRAS wild-type (wt) metastatic colorectal cancer (mCRC).
Authors: Ciuleanu T. , Nikolic V. , Shmueli E. , Vrbanec D. , Plate S. , Krmpotic Z. M. , Dank M. , Purkalne G. , Brodowicz T. , Zielinski C. 
Published: February 2017

494 Background: FOLFOX4 + q1w cetuximab is a standard 1st-line regimen in KRAS wt mCRC. This trial evaluated FOLFOX4 + q1w cetuximab (Arm A) and FOLFOX4 + q2w cetuximab (Arm B) as 1st-line therapy in KRAS wt mCRC. Methods: Pts with KRAS wt mCRC were randomized to q1w cetuximab (400 mg/m2initial dose then 250 mg/m2/wk) or q2w cetuximab (500 mg/m2 every 2 wks). Both arms received FOLFOX4 (folinic acid 200 mg/m2, then 5-FU 400 mg/m2bolus, then 5-FU 600mg/m2 over 22 h on days 1+2, plus oxaliplatin 85 mg/m2 on day 1 q2w). Primary endpoint is objective response rate (ORR) which was analyzed in a protocol specified interim analysis. Secondary efficacy endpoints are progression- free survival (PFS) and overall survival. Results: From Sep 2007 to Sep 2009, 152 pts with KRAS wt tumors (22 centers in 12 countries) were randomized and received ≥1 dose of study treatment, arm A (n=75) and arm B (n=77). Baseline characteristics were well balanced (A vs B): mean age: 57 vs 60 years, Karnofsky Performance Score (PS) 80: 15% vs 18%, PS 90: 45% vs 40%, PS 100: 40% vs 42%, male gender: 40% vs 45%, prior adjuvant or neoadjuvant therapy: 23% vs 17%, metastases at initial diagnosis: 65% vs 64%, and >2 involved organs: 24% vs 29%. Median follow up was 12 months. ORR (CR + PR) was 51% in arm A and 63% in arm B, respectively, the difference between arm B and A was 12% (95% CI: -4% to 27%). Preliminary results for PFS time did not indicate relevant differences between both arms. Mature PFS results will be presented at the symposium. Based on current data, most common grade 3-4 adverse events (≥ 10% in any arm, A vs B) were neutropenia/neutrophil count decreased in 32 vs 34%, rash in 15 vs 16% and diarrhea in 7 vs 10% of the pts. Conclusions: These data suggest that cetuximab q2w has comparable efficacy and an equivalent safety profile as q1w dosing in combination with FOLFOX4. Data collection and analysis is ongoing. [Table: see text] [Table: see text]
Effective management of patients receiving XELOX: Evaluation of impact of dose modifications on outcome in patients from the NO16966, NO16967, and NO16968 trials.
Authors: Cassidy J. , Cox J. V. , Scotto N. , Schmoll H. 
Published: February 2017

497 Background: In patients (pts) with metastatic colorectal cancer (MCRC), XELOX is non-inferior to FOLFOX4 in terms of PFS and OS as either first-line (NO16966, Cassidy et al. JCO 2008) or second-line therapy (NO16967, Rothenberg et al. Ann Oncol 2008). In pts with stage III colon cancer (NO16968, Haller et al. ECCO-ESMO 2009), adjuvant XELOX is superior to 5-FU/LV in terms of DFS. While XELOX is generally well tolerated, regional differences in fluoropyrimidine tolerability were noted in a pooled analysis [Rothenberg et al. ASCO GI 2008], leading to use of lower than recommended doses of capecitabine (i.e. 1,000mg/m2 bid d1–15 with oxaliplatin 130mg/m2 d1 q3w) in some countries. Methods: NO16966, NO16967 and NO16968 protocols included standard dose/schedule modifications for capecitabine, 5-FU and oxaliplatin for treatment-related adverse events (AEs). Safety parameters included AEs, deaths, laboratory parameters, exposure to trial medication, and withdrawals. In NO16966 and NO16967, Kaplan-Meier curves for PFS were developed for pts with no treatment modifications, and pts with dose reductions, treatment interruptions or cycle delays to assess the effect of treatment modifications on efficacy. NO16968 also included a planned analysis of the effect of dose modifications on DFS. Results: NO16966 included 1335 pts with previously untreated MCRC receiving XELOX or FOLFOX4. NO16967 included 627 pts with previously treated MCRC receiving XELOX or FOLFOX4. NO16968 included 1886 pts with resected stage III disease receiving XELOX or 5-FU/LV; dose modifications were required for capecitabine in 65% and oxaliplatin in 62% of pts in NO16968. Kaplan-Meier curves of PFS (NO16966/NO16967) or DFS (NO16968) for pts who did and did not require dose modifications indicated that the efficacy of XELOX did not appear to be compromised by dose modifications. Indeed, pts who required dose modifications seemed to have a favourable outcome compared with those who did not. Conclusions: From these data we cannot make a recommendation that initial dosing should be lower than the labeled dose. However, it is clear that dose modification does not seem to impact patient outcome. [Table: see text]