bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between the development of rash and clinical and quality of life outcomes by Kras mutation status in patients with colorectal cancer treated with cetuximab in NCIC CTG CO.17.
Authors: O'Callaghan C. J. , Tu D. , Karapetis C. S. , Au H. , Moore M. J. , Tebbutt N. C. , Trudeau M. G. , Price T. J. , Yip D. , Jonker D. J. 
Published: February 2017

481 Background: The NCIC Clinical Trials Group CO.17 trial, conducted with the Australasian Gastrointestinal Trials Group, showed cetuximab monotherapy (CET vs. best supportive care [BSC]) improved overall (OS) and progression-free survival (PFS) and maintained quality of life (QoL) in patients previously treated for advanced colorectal cancer. Correlative analyses showed strong relationships between CET benefits and both rash development and Kras mutation status. Association between rash and CET benefits is now presented by Kras mutation status. Methods: Rash was graded weekly by NCI CTC 2.0 criteria. Landmark-type analyses (LTA) were performed by excluding patients who died within 28 days and then grouping by rash severity (gr 2+ vs. gr 0/1) based both on worst grade ever developed (LTA1) and worst grade on or before day 28 (LTA2). Multivariate Cox models were conducted separately for wild-type (WT) and mutated (MUT) Kras tumors. Results: More rash of severity gr 2+ was observed in WT than MUT patients treated with CET (57.3% vs. 44.4%; p = 0.08). The median OS, PFS, and HRs from LTA2 are presented for WT and MUT groups (see Table). Conclusions: Rash severity was positively correlated with PFS and OS in Kras WT patients who received CET, although only for gr 2+ rash did OS significantly exceed that of BSC patients. In Kras MUT patients, neither gr 0/1 nor gr 2+ rash was associated with either improved PFS or OS vs. BSC patients. Quality of life outcomes will also be reported by Kras mutation status. [Table: see text] [Table: see text]
Pushing the envelope beyond a centimeter in rectal cancer: Oncologic implications of close but negative margins.
Authors: Fitzgerald T. L. , Brinkley J. , Zervos E. E. 
Published: February 2017

487 Background: Advances in surgery, adjuvant therapy and understanding of the natural history of rectal cancer has enabled sphincter preservation surgery for most patients. A 1 cm margin is commonly accepted as minimal distal margin, when not achievable many are relegated to permanent colostomy. Our purpose was to determine if distal margins of < 1 cm is justified by the world's published experience. Methods: Studies were identified with a MEDLINE search using terms rectal cancer, colorectal cancer, margins and distal margins with an additional manual search. There were no restrictions on data type or year of publication. All studies were retrospective or prospective, none were randomized controlled. Studies were excluded if specific margins, local recurrence rates or case level data could not be extracted. Extracted variables included year of publication, time span, number of patients, standardized surgery, radiotherapy, margins, follow up, local recurrence rates and overall survival. Meta-analysis was performed using a random weighting scheme. Values were aggregated across studies to determine overall impact and p-values. Results: Seventeen studies reported margins with thirteen studies, 3,232 patients, reporting outcomes when < 1cm. Meta-analysis of all studies indicated a nonsignificant trend favoring greater margins. However, in order to understand distal margins in the context of current standards additional analyses were performed. Of the thirteen studies 4 reported neither TME nor use adjuvant radiotherapy and 9 studies reported use of one or both. When either total mesorectal excision and/or adjuvant radiotherapy was reported there was no significant increase in local recurrence with distal margins < 1 cm. In studies that used neither therapy > 1 cm margins were statistically less prone to recurrence. Conclusions: Sphincter preservation is possible with < 1 cm distal margin when optimal surgical and adjuvant therapy are applied. [Table: see text]
Use of class III beta tubulin to predict efficacy from paclitaxel- or docetaxel-based chemotherapy in patients with advanced gastric cancer.
Authors: Ahn J. , Jung M. , Chang H. , Zhang X. , Jeung H. , Kim T. , Roh J. K. , Chung H. C. , Rha S. Y. 
Published: February 2017

52 Background: To predict clinical outcome in patients with advanced gastric cancer (AGC) received paclitaxel or docetaxel based chemotherapy, we evaluated expression of class III beta tubulin (bTubIII). Methods: Expression of bTubIII was evaluated by immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded tumors from the primary gastric cancer. Tumors were classified as bTubIII “low” and “high” according to median of IHC score [intensity (0-3) × portion (0-100)]. The expression of bTubIII was investigated for their association with clinical outcomes of efficacy and toxicity. Results: One hundred twenty-four AGC pts who were treated with paclitaxel or docetaxel combined with an infusional 5-fluorouracil and low-dose leucovorin as first and second-line palliative chemotherapy were enrolled. Thirty-three patients (26.7%) were confirmed to have high expression of bTubIII. The patients with high expression of bTubIII showed higher disease control rate (DCR) and longer progression-free survival (PFS) than those with low expression in patients treated with paclitaxel (79.3 % vs. 57.3 %, p = 0.039, and 3.0 months vs. 1.5 months, p = 0.073). By contrast, there was no difference of DCR and PFS according to expression of bTubIII in patients treated with docetaxel. The expression of bTubIII was not associated with toxicity in both patients treated with paclitaxel or docetaxel. Conclusions: The expression of bTubIII may be a predictive marker in AGC patients received paclitaxel based chemotherapy, but not docetaxel. No significant financial relationships to disclose.
A randomized phase II trial of chemoradiotherapy with oral fluoropyrimidine inhibitory for dihydropyrimidine dehydrogenase for low rectal cancer: An interim report.
Authors: Nishioka M. , Shimada M. , Kurita N. , Iwata T. , Morimoto S. , Yoshikawa K. , Higashijima J. , Miyatani T. , Kashihara H. , Mikami C. 
Published: February 2017

524 Background: Preoperative chemoradiotherapy (CRT) has been widely used to improve local control of disease and to preserve anal sphincter in the treatment of rectal cancer. However, the response to CRT differs among individual tumors. In ASCO 2008 Gastrointestinal Cancers Symposium, we reported that the patients with up-regulation of 17 genes were suggested to be good responder of CRT. Our purpose of this study was to evaluate the toxicity and efficacy of CRT using UFT versus S-1 and explore biomarkers for response in patients with locally advanced rectal cancer. Methods: Fifty patients who received preoperative CRT (40Gy radiotherapy) were randomly assigned to either UFT or S-1. UFT and S-1 were administered during the radiotherapy course. S-1 was a novel oral fluoropyrimidine inhibitory for dihydropyrimidine dehydrogenase and had potent radiosensitizing property. Biopsy specimens were obtained from rectal cancer before preoperative CRT and were analyzed by focused DNA microarray (132 genes). To pick up the predictive factors, the 132 genes were selected in the view of sensitivity of 5FU. Response to CRT was determined by RECIST and histopathologic examination of surgically resected specimens and classified as responders (CR, PR and grade 2, 3) or nonresponders (SD, PD and grade 0, 1). Results: UFT group (n=25) and S-1 group (n=25) were enrolled. Response rate (grade 2 or 3) to CRT determined by histopathologic examination of surgically resected specimens was 58% in the UFT group and was 75% in the S-1 group. Response rate evaluated by RECIST criteria was 62% in the UFT group and was 77% in the S-1 group. National Cancer Institute Common Toxicity Criteria grade 2 or 3 toxicity was observed in 8% of the patients in the UFT group and 23% of patients in the S-1 group. Grade 2 or 3 toxicity in the UFT group was neutropenia and was diarrhea, neutropenia and dermatitis in the S-1 group. In ASCO 2010, we will report each candidate biomarker genes for response to CRT in the UFT and S-1 group. Conclusions: The results have suggested that CRT using UFT or S-1 is feasible and effective for patients with locally advanced rectal cancer. [Table: see text]
Treatment patterns and health care resource utilization of metastatic colorectal cancer (mCRC) patients who received bevacizumab or cetuximab in second-line regimen.
Authors: Yang H. , Yu A. P. , Yim Y. , Yu E. , Wu E. 
Published: February 2017

525 Background: Targeted therapies such as bevacizumab (BV) and cetuximab (CX) are important treatment options in mCRC. Real-world treatment patterns and resource utilization of mCRC patients (Pts) receiving BV and CX in second-line (2L) treatment are not well studied. Methods: Pts with mCRC were identified from the PharMetrics pharmacy and medical insurance claims database (2002-2009). Included Pts received BV or CX in 2L therapy. 2L was defined as change in therapy from first-line (1L) at least 4 weeks after 1L initiation. Healthcare resource utilization and costs were evaluated during the 6 months following 2L start. Results: A total of 2,188 Pts were included in the analysis, including 1,808 2L BV Pts and 380 2L CX Pts. Demographic and baseline characteristics were similar between groups. Pts' mean age was 61 years and 56% were male. Among all study Pts, 34.1% and 2.7% received BV and CX in 1L, respectively. 60.1% of Pts received oxaliplatin-based regimens in 1L. In 2L, irinotecan and oxaliplatin containing regimens were most commonly used. During the 6 months period following 2L therapy start, BV vs. CX Pts incurred significantly lower risk-adjusted total costs (difference: -$10,231, p=0.020) and inpatient costs ($-3,681, p<0.001). Mean targeted therapy cost was significantly higher for CX ($33,425) than BV ($23,622) (-$10,260, p<0.001). BV Pts incurred significantly less inpatient visits (0.5 vs. 0.7, p<0.001) compared to CX Pts and shorter duration of total hospital stay (3.6 vs. 5.6 days, p=0.007). Conclusions: In 2L treatment of mCRC Pts in the real world setting, BV was most used with oxaliplatin- and irinotecan-based regimens, whereas CX was commonly used with irinotecan-based regimens. Overall, less healthcare resource utilization and costs were observed in patients treated with 2L BV compared to 2L CX. Use of BV in 2L treatment of mCRC was associated with lower number of claims for targeted agents, lower healthcare costs and fewer hospitalizations than CX. [Table: see text] [Table: see text]
Phase I results of the randomized, placebo controlled, phase I/II study of the novel oral c-Met inhibitor, ARQ 197, irinotecan (CPT-11), and cetuximab (C) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC) who have received front-line systemic therapy.
Authors: Eng C. , Bendell J. C. , Bessudo A. , Gabrail N. Y. , Diamond J. , Pande A. U. , Gorbatchevsky I. 
Published: February 2017

527 Background: ARQ 197 selectively inhibits the c-Met receptor tyrosine kinase (RTK), which has been implicated in tumor cell migration, invasion, proliferation, and angiogenesis. CPT-11 plus C is a standard of care for CPT-11-refractory mCRC pts with WT KRAS tumors. Resistance to C has been associated with activation of alternative RTK pathways including c-Met. We hypothesize that adding ARQ 197 to CPT-11 plus C may decrease resistance to C therapy and improve pt outcomes. Methods: The primary objectives of phase I were to evaluate safety and tolerability of ARQ 197 administered in combination with CPT-11 plus C, and to define a recommended phase II dose (RPTD). Pts with surgically unresectable locally advanced or mCRC who received at least 1 prior line of chemotherapy, KRAS WT and ECOG performance status < 2 were eligible. Cohorts of 3 pts each were treated with CPT-11 (180 mg/m2) and C (500 mg/m2) every 2 weeks along with escalating doses of ARQ 197 (120, 240, 360 mg) PO BID. Blood and tissue were collected for PK, biomarker, and other analyses. If no DLTs were observed during the first 28-day cycle in 3 pts treated in cohort 3, 360 mg BID would be defined as the RPTD. Responses were assessed every 8 weeks per RECIST v1.1. Results: Nine pts were treated in 3 cohorts. Median age: 53 yrs (range 30-77); ECOG PS 0/1: 4/5; median prior therapies: 2 (range 1-4). No DLTs were observed. The RPTD for ARQ 197 was 360 mg BID. To date, two pts have discontinued (1 disease progression and 1 withdrew consent after achieving complete response) and 7 pts remain on study. The reported grade 3/4 adverse events were: neutropenia (3/4: 1/1), and one case each of grade 3 fatigue, leucopenia, acneiform rash, vomiting, anemia and syncope. Preliminary efficacy data in 9 evaluable pts include 1 CR (after 4 cycles), 2 PR (after 2 cycles), 5 SD, and 1 PD as best response. Conclusions: The combination of ARQ 197 and CPT-11 plus C was well tolerated with encouraging preliminary antitumor activity. The RPTD for ARQ 197 was 360 mg BID. The randomized phase II portion of the study continues accrual. [Table: see text]
Racial/ethnic differences in use of surgery and adjuvant chemotherapy for nonmetastatic colon cancer: Where's the rub?
Authors: Yang J. , Mauldin P. , Ebeling M. , Hulsey T. , Thomas M. B. , Esnaola N. F. 
Published: February 2017

529 Background: Disparities in receipt of recommended medical therapy for colon cancer have been reported. The objective of this study was to determine the independent effect of black race and Hispanic ethnicity on use of surgery/adjuvant therapy in patients (pts) with nonmetastatic colon cancer, controlling for surgical/medical oncology consultation Methods: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified 26,946 pts aged 66 and older with resected stage I-III colon cancer diagnosed between 1999-2004. Surgical/medical oncology consultation and receipt of chemotherapy were ascertained from Medicare claims. The relationships between patient/tumor characteristics, surgical/medical oncology consultation, and use of surgery/adjuvant therapy were analyzed using chi square tests. Odds ratios (OR) of receipt of surgery/chemotherapy were calculated using logistic regression analysis. Results: We identified 23,834 white, 2,022 black, and 1,090 Hispanic pts with stage I (7,088 pts), stage II (9,510 pts), and stage III (7,236 pts) colon cancer. Blacks and Hispanics were more likely to be younger, less educated, of lower income, and have greater comorbidity compared to whites. Rates of surgical resection were lower among blacks than Hispanics (86.6% vs. 88.8% vs. 92.0% in whites, all p < 0.001). Blacks with stage III colon cancer (but not Hispanics) were also less likely to receive adjuvant chemotherapy (48.2% vs. 54.7% in whites, p < 0.001). After controlling for socioeconomic status, comorbidity, and surgical/medical oncology consultation, black race (but not Hispanic ethnicity) was independently associated with underuse of surgery (adjusted OR, 0.68; 95% confidence interval [CI], 0.51-0.89) and adjuvant chemotherapy (adjusted OR, 0.71; 95% CI, 0.60-0.85). Conclusions: Black race, but not Hispanic ethnicity, is a powerful, independent predictor of underuse of surgery and adjuvant chemotherapy in pts with nonmetastatic colon cancer. Qualitative studies are needed to determine whether patient misperceptions about colon cancer surgery/chemotherapy or suboptimal physician-patient interactions may underlie these observations. No significant financial relationships to disclose.
Clinical outcomes in patients age 40 or younger at diagnosis of synchonous metastatic colorectal cancer.
Authors: Lowery M. A. , Gallagher D. J. , Kemeny N. E. 
Published: February 2017

531 Background: The impact of age ≤ 40 at diagnosis of colorectal cancer on outcome is unclear. The higher incidence of tumor microsatellite instability (MSI) in young patients may confound the estimation of survival in this population due to the more favorable biology associated with MSI cancers. Methods: All pts diagnosed with metastatic colorectal adenocarcinoma at ≤ 40 years old between Jan 2000-Jan 2010 were identified from the institutional database with prior IRB approval. Clinical and pathology records were reviewed. Only patients with synchronous metastases at presentation were included. Immunohistochemistry for DNA mismatch repair proteins (MMR) was performed in 40 pts of whom 5 had loss of MMR and were excluded from the analysis. Results: 185 pts were identified; median age at diagnosis was 36 years (range 18–40) Primary site was in the right colon in 50 cases (27%). All pts received at least one line of systemic chemotherapy. For pts receiving systemic therapy median survival was 23.4 months and for those receiving hepatic arterial infusion (HAI) plus systemic the median survival was 48.2 months. Median survival for those who underwent liver resection (78 pts) was 54.6 months. Other factors such as race, post partum and KRAS mutation impacted on survival as shown below. Conclusions: Overall survival in this cohort of young pts is similar to that observed in clinical trials of modern combination therapy for metastatic CRC. African American race, presence of a KRAS mutation, and presentation following pregnancy may be associated with reduced survival in this group. [Table: see text] No significant financial relationships to disclose.
Phase Ib study of drozitumab combined with cetuximab (CET) plus irinotecan (IRI) or with FOLFIRI with or without bevacizumab (BV) in previously treated patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Baron A. D. , O'Bryant C. L. , Choi Y. , Royer-Joo S. , Portera C. C. 
Published: February 2017

532 Background: Drozitumab is a monoclonal antibody that triggers tumor cell apoptosis by selective agonistic interaction with the Apo2 ligand/TNF-related apoptosis-inducing ligand death receptor 5. This study assessed the safety of drozitumab combined with two standard IRI- containing regimens in previously treated mCRC pts. Methods: Multicenter, open-label, dose-escalation study with treatment until disease progression or treatment intolerance. For CET+IRI regimen (Cohorts 1-4), a 21-day cycle (cy) = drozitumab on Day 1 at escalating doses of 1, 4, 10, or 15mg/kg, IRI on Day 1, and CET on Days 1, 8, and 15. For FOLFIRI (Cohort 5), a 14-day cy = drozitumab on Day 1 given as a 10 mg/kg loading dose followed by 7 mg/kg in continuing cys, with FOLFIRI (plus BV in pts not previously treated with BV) on Day 1. Dose-limiting toxicity (DLT) was assessed through 2 doses of drozitumab (29 days for CET+IRI; 28 days for FOLFIRI). Adverse events (AE) were recorded through all cys. Response was assessed by RECIST. Results: 14 pts received a median of 6.5 cys (range 2-21) of drozitumab with CET+IRI and 6 pts received a median of 12 cys (range 3-21) of drozitumab with FOLFIRI. No DLTs occurred at the time of dose escalation. The most frequent AEs were diarrhea (85%), fatigue (80%), nausea (80%), alopecia (70%), neutropenia (70%), and decreased appetite (50%). Most of the toxicities were grades 1-2. The most frequent grade ≥3 AEs were neutropenia (60%), diarrhea (15%), hypokalemia (15%), and leukopenia (15%). Two pts discontinued due to AEs: 1 grade 2 fatigue, 1 grade 3 pyrexia. Among the 20 total pts, best responses included 3 partial responses (2 confirmed, 1 unconfirmed), 12 stable disease and 5 progressive disease. The study enrollment was stopped early by the sponsor for reasons unrelated to safety or efficacy. Conclusions: The addition of drozitumab to two standard second-line IRI-containing regimens (CET+IRI or FOLFIRI ± BV) was well tolerated in mCRC pts. AEs were similar to those previously reported for the chemotherapy alone. Tumor responses suggest no adverse interactions between drozitumab and the chemotherapy evaluated in this study. [Table: see text]
The extent of lymphadenectomy and overall survival depend on the timing of radiotherapy for rectal cancer.
Authors: Le M. N. , Mailey B. A. , Lee W. , Duldulao M. P. , Garcia-Aguilar J. , Kim J. 
Published: February 2017

540 Background: Accurate staging and local disease control depend on the extent of lymphadenectomy (LAD) in rectal cancer. Previous studies suggest that lymph node (LN) number varies with neoadjuvant therapies. Our objectives were to measure the impact of timing of radiotherapy on extent of LAD and to determine the prognostic role of LN number in rectal cancer. Methods: Patients undergoing curative-intent surgery for rectal adenocarcinoma (1988-2006) in Los Angeles County were identified from the Cancer Surveillance Program. Patients were grouped according to radiotherapy timing (neoadjuvant, adjuvant, or none). To measure prognostic significance, an optimal cutoff was assessed for patients with N0 disease by dichotomizing LN numbers from 3-7. Results: Query of the registry identified 6,358 patients. Of these, 20% (n = 1,280), 25% (n = 1,573), and 55% (n = 3,545) received neoadjuvant, adjuvant, and no radiotherapy, respectively. There was no difference in LN number in patients with and without radiotherapy (7 vs. 8 LNs, p = NS). However, within the radiotherapy cohort, there was significantly lower LNs in the neoadjuvant group (5 vs. 9 LNs, respectively; p < 0.001). Survival differences favored the groups with higher LN number. The optimal LN cutoff with no survival difference was 7 in the adjuvant radiotherapy group; there was no optimal cutoff for neoadjuvant therapy patients. Conclusions: From our population-based cohort, we observed that patients receiving neoadjuvant radiotherapy had decreased LN retrieval and that LN number was non-prognostic. In contrast, the extent of LAD is a prognostic factor for overall survival in patients receiving adjuvant radiotherapy. [Table: see text] No significant financial relationships to disclose.
How to reduce the risk of recurrence after surgical treatment of colorectal liver metastases?
Authors: Benhaim L. , Goárá D. , Bonnet S. , Dumont F. , Malka D. , Ducreux M. , Eveno C. , Elias D. 
Published: February 2017

544 Background: After surgery with curative intent for colorectal liver metastases (MHCCR), liver recurrence occurs in more than 60% of patients, despite the administration of adjuvant systemic chemotherapy. The objective of this study was to compare the prognosis of patients operated on MHCCR with high risk of recurrences in the liver, treated by postoperative chemotherapy hepatic arterial infusion (HAI) by oxaliplatin, to that obtained after adjuvant systemic chemotherapy. Methods: From January 2000 to December 2009, 113 patients who underwent curative resection of more than 3 MHCCR, were selected from a prospective database. Among these 113 patients, 47 had received postoperative HAI associated with systemic chemotherapy (HAI+) and 66, systemic chemotherapy alone (HAI-). Results: The two groups were comparable in age, sex, stage of primary, rates of synchronous (> 75%), and bilobar (> 90%) MHCCR. The number of MHCCR was significantly higher in the group HAI+ (p < 0.0001). Twenty-seven patients (57%) received more than 6 courses of HAI. HAI was discontinued in 6 patients (12%) due to technical problems with the catheter. After a median follow up of 75 months (7-125), the overall survival and recurrence-free survival at 5 years were higher for patients HAI+ compared to those HAI-, respectively 52.9% vs. 12.3% (p = 0.06) and 30.8% vs. 2% (p < 0.0001). Conclusions: The postoperative administration of oxaliplatin-based HAI associated to systemic chemotherapy after cure of MHCCR, improves recurrence-free survival of patients at high risk of hepatic recurrence, compared to systemic chemotherapy alone. No significant financial relationships to disclose.