Predictive and prognostic roles of BRAF mutation in stage III colon cancer: results from intergroup trial CALGB 89803.

Purpose: Alterations in the RAS-RAF-MAP2K (MEK)-MAPK signaling pathway are major drivers in colorectal carcinogenesis. In colorectal cancer, BRAF mutation is associated with microsatellite instability (MSI), and typically predicts inferior prognosis. We examined the effect of BRAF mutation on survival and treatment efficacy in patients with stage III colon cancer.

A genome-wide association study of overall survival in pancreatic cancer patients treated with gemcitabine in CALGB 80303.

Background And Aims: Cancer and Leukemia Group B 80303 was a randomized, phase III study in patients with advanced pancreatic cancer treated with gemcitabine plus either bevacizumab or placebo. We prospectively collected germline DNA and conducted a genome-wide association study (GWAS) using overall survival (OS) as the endpoint.

Experimental Design: DNA from 351 patients was genotyped for more than 550,000 single-nucleotide polymorphisms (SNP).

Relationship between statin use and colon cancer recurrence and survival: results from CALGB 89803.

Background: Although preclinical and epidemiological data suggest that statins may have antineoplastic properties, the impact of statin use on patient survival after a curative resection of stage III colon cancer is unknown.

Methods: We conducted a prospective observational study of 842 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial from April 1999 to May 2001 to investigate the relationship between statin use and survival. Disease-free survival (DFS), recurrence-free survival (RFS), and overall survival (OS) were investigated by Kaplan-Meier curves and log-rank tests in the overall study population and in a subset of patients stratified by KRAS mutation status (n = 394), and Cox proportional hazards regression was used to assess the simultaneous impact of confounding variables.

A phase 2 trial of gemcitabine, 5-fluorouracil, and radiation therapy in locally advanced nonmetastatic pancreatic adenocarcinoma : cancer and Leukemia Group B (CALGB) 80003.

Background: The purpose of this study was to assess the efficacy and safety of 5-fluorouracil (5FU) and gemcitabine administered concurrently with radiation in patients with locally advanced, nonmetastatic pancreatic cancer.

Methods: Eligible patients had histologically confirmed pancreatic adenocarcinoma deemed locally unresectable without evidence of metastatic disease. In addition, all patients underwent laparoscopy or laparotomy before study entry to rule out peritoneal carcinomatosis.

A Cancer and Leukemia Group B phase II study of sunitinib malate in patients with previously treated metastatic pancreatic adenocarcinoma (CALGB 80603).

Background: The Cancer and Leukemia Group B (CALGB) conducted a phase II study evaluating sunitinib in patients with progressive metastatic pancreas adenocarcinoma following prior gemcitabine-based therapy (trial CALGB 80603; ClinicalTrials.gov identifier, NCT00397787). The primary endpoint was to determine the disease control rate (DCR) as measured by the Response Evaluation Criteria in Solid Tumors (complete response, partial response [PR], and stable disease) at 6 weeks.

Multivitamin use is not associated with cancer recurrence or survival in patients with stage III colon cancer: findings from CALGB 89803.

Purpose: Multivitamin use is widespread in the United States, especially among patients with cancer. However, the influence of multivitamin supplementation on cancer recurrence and death after a curative resection of colon cancer is unknown.

Patients And Methods: We conducted a prospective, observational study of 1,038 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial.

Factors associated with the development of brain metastases: analysis of 975 patients with early stage nonsmall cell lung cancer.

Background: The risk of developing brain metastases after definitive treatment of locally advanced nonsmall cell lung cancer (NSCLC) is approximately 30%-50%. The risk for patients with early stage disease is less defined. The authors sought to investigate this further and to study potential risk factors.

Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303).

Purpose: The combination of gemcitabine plus bevacizumab produced a 21% response rate and a median survival of 8.8 months in a multicenter phase II trial in patients with metastatic pancreatic cancer. These encouraging data led Cancer and Leukemia Group B (CALGB) to conduct a double-blind, placebo-controlled, randomized phase III trial of gemcitabine/bevacizumab versus gemcitabine/placebo in advanced pancreatic cancer patients.

Impact of smoking on patients with stage III colon cancer: results from Cancer and Leukemia Group B 89803.

Background: Cigarette smoking has been shown to increase the risk of developing colorectal cancer, particularly smoking early in life. Little is known about the impact of tobacco use on colon cancer recurrence among colon cancer survivors.

Methods: The authors prospectively collected lifetime smoking history from stage III colon cancer patients enrolled in a phase 3 trial via self-report questionnaires during and 6 months after completion of adjuvant chemotherapy.

KRAS mutation in stage III colon cancer and clinical outcome following intergroup trial CALGB 89803.

Purpose: Alterations in the RAS and RAF pathway relate to epigenetic and epigenomic aberrations, and are important in colorectal carcinogenesis. KRAS mutation in metastatic colorectal cancer predicts resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy (cetuximab or panitumumab). It remains uncertain, however, whether KRAS mutation predicts prognosis or clinical outcome of colon cancer patients independent of anti-EGFR therapy.

Timing of local and distant failure in resected lung cancer: implications for reported rates of local failure.

Introduction: Most adjuvant lung cancer trials only report first sites of failure. The relative timing of local (i.e.

Randomized phase II study of gemcitabine administered at a fixed dose rate or in combination with cisplatin, docetaxel, or irinotecan in patients with metastatic pancreatic cancer: CALGB 89904.

Purpose: The relative value of gemcitabine-based combination chemotherapy therapy and prolonged infusions of gemcitabine in patients with advanced pancreatic cancer remains controversial. We explored the efficacy and toxicity of gemcitabine administered at a fixed dose rate or in combination with cisplatin, docetaxel, or irinotecan in a multi-institutional, randomized, phase II study.

Patients And Methods: Patients with metastatic pancreatic cancer were randomly assigned to one of the following four regimens: gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 with cisplatin 50 mg/m(2) on days 1 and 15 (arm A); gemcitabine 1,500 mg/m(2) at a rate of 10 mg/m(2)/min on days 1, 8, and 15 (arm B); gemcitabine 1,000 mg/m(2) with docetaxel 40 mg/m(2) on days 1 and 8 (arm C); or gemcitabine 1,000 mg/m(2) with irinotecan 100 mg/m(2) on days 1 and 8 (arm D).

Local recurrence after surgery for early stage lung cancer: an 11-year experience with 975 patients.

Background: The objective of the current study was to evaluate the actuarial risk of local failure (LF) after surgery for stage I to II nonsmall cell lung cancer (NSCLC) and assess surgical and pathologic factors affecting this risk.

Methods: The records, including pertinent radiologic studies, of all patients who underwent surgery for T1 to T2, N0 to N1 NSCLC at Duke University between 1995 and 2005 were reviewed. Risks of disease recurrence were estimated using the Kaplan-Meier method.

Regional lung density changes after radiation therapy for tumors in and around thorax.

Purpose: To study the temporal nature of regional lung density changes and to assess whether the dose-dependent nature of these changes is associated with patient- and treatment-associated factors.

Methods And Materials: Between 1991 and 2004, 118 patients with interpretable pre- and post-radiation therapy (RT) chest computed tomography (CT) scans were evaluated. Changes in regional lung density were related to regional dose to define a dose-response curve (DRC) for RT-induced lung injury using three-dimensional planning tools and image fusion.

Phase I and pharmacokinetic study of sorafenib in patients with hepatic or renal dysfunction: CALGB 60301.

Purpose: We sought to characterize the pharmacokinetics (PK) and determine a tolerable dose of oral sorafenib in patients with hepatic or renal dysfunction.

Patients And Methods: Patients were assigned to one of nine cohorts: cohort 1, bilirubin < or = upper limit of normal (ULN) and AST < or = ULN and creatinine clearance (CC) > or = 60 mL/min; cohort 2, bilirubin more than ULN but < or = 1.5x ULN and/or AST more than ULN; cohort 3, CC between 40 and 59 mL/min; cohort 4, bilirubin more than 1.

Association between RT-induced changes in lung tissue density and global lung function.

Purpose: To assess the association between radiotherapy (RT)-induced changes in computed tomography (CT)-defined lung tissue density and pulmonary function tests (PFTs).

Methods And Materials: Patients undergoing incidental partial lung RT were prospectively assessed for global (PFTs) and regional (CT and single photon emission CT [SPECT]) lung function before and, serially, after RT. The percent reductions in the PFT and the average changes in lung density were compared (Pearson correlations) in the overall group and subgroups stratified according to various clinical factors.

Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group.

Purpose: Imatinib mesylate is standard treatment for patients who have advanced gastrointestinal stromal tumor (GIST), but not all patients benefit equally. In previous studies, GIST genotype correlated with treatment outcome and optimal imatinib dosing.

Patients And Methods: We examined the relationship between kinase genotype and treatment outcome for 428 patients enrolled on the North American phase III study SWOG S0033/CALGB 150105 and treated with either 400 mg or 800 mg daily doses of imatinib.

Impact of body mass index and weight change after treatment on cancer recurrence and survival in patients with stage III colon cancer: findings from Cancer and Leukemia Group B 89803.

Purpose: Obesity is a risk factor for the development of colon cancer. However, the influence of body mass index (BMI) on the outcome of patients with established colon cancer remains uncertain. Moreover, the impact of change in body habitus after diagnosis has not been studied.

Dose-dependent effects of radiation therapy on cerebral blood flow, metabolism, and neurocognitive dysfunction.

Purpose: A prospective study was performed to formally relate dose-dependent radiologically defined changes in normal brain induced by radiotherapy (RT) to neurocognitive dysfunction in subjects with primary brain tumors.

Methods And Materials: Adult patients receiving three-dimensional RT for central nervous system (CNS) tumors were enrolled. Positron emission tomography (PET) scanning and neuropsychological testing were performed before RT and 3 weeks and 6 months after treatment.

Association of family history with cancer recurrence and survival among patients with stage III colon cancer.

Context: A family history of colorectal cancer in a first-degree relative increases the risk of developing colorectal cancer. However, the influence of family history on cancer recurrence and survival among patients with established disease remains uncertain.

Objective: To examine the association of family history of colorectal cancer with cancer recurrence and survival of patients with colon cancer.

Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781.

Purpose: The primary treatment modality for patients with carcinoma of the esophagus or gastroesophageal junction has been surgery, although primary radiation therapy with concurrent chemotherapy produces similar results. As both have curative potential, there has been great interest in the use of trimodality therapy. To this end, we compared survival, response, and patterns of failure of trimodality therapy to esophagectomy alone in patients with nonmetastatic esophageal cancer.

A phase II prospective multi-institutional trial of adjuvant active specific immunotherapy following curative resection of colorectal cancer hepatic metastases: cancer and leukemia group B study 89903.

Background: Patients with curatively resected colorectal cancer hepatic metastases often harbor occult metastatic disease and are at high risk of experiencing recurrence. This patient cohort is ideally suited to test novel therapies such as immunotherapy. We treated patients-post-hepatic resection-with anti-idiotype monoclonal antibody vaccines to the tumor-associated antigens carcinoembryonic antigen (CeaVac) and human milk fat globule (TriAb), both of which are co-expressed in more than 90% of colorectal cancer patients.

Prospective assessment of radiotherapy-associated cardiac toxicity in breast cancer patients: analysis of data 3 to 6 years after treatment.

Background: Radiation therapy (RT) to the left breast/chest wall has been linked with cardiac dysfunction. Previously, the authors identified cardiac perfusion defects in approximately 50% to 60% of patients 0.5 to 2 years post-RT.

Association of dietary patterns with cancer recurrence and survival in patients with stage III colon cancer.

Context: Dietary factors have been associated with the risk of developing colon cancer but the influence of diet on patients with established disease is unknown.

Objective: To determine the association of dietary patterns with cancer recurrences and mortality of colon cancer survivors.

Design, Setting, And Patients: Prospective observational study of 1009 patients with stage III colon cancer who were enrolled in a randomized adjuvant chemotherapy trial (CALGB 89803) between April 1999 and May 2001.

Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803.

Purpose: Randomized studies have shown that irinotecan (CPT-11) extends survival in metastatic colorectal cancer patients when administered in second-line and when added to fluorouracil (FU) plus leucovorin (LV) in first-line therapy of metastatic colorectal cancer. When this study was initiated, FU plus LV was standard adjuvant treatment for stage III colon cancer. We evaluated the efficacy and safety of weekly bolus CPT-11 plus FU plus LV in the treatment of patients with completely resected stage III colon cancer.