PubMed | Georgetown University, University of Chicago, University of California at Los Angeles, City of Hope Comprehensive Cancer Center and 6 more.
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2016
KRAS mutations in NSCLC are associated with a lack of response to epidermal growth factor receptor inhibitors. Selumetinib (AZD6244; ARRY-142886) is an oral selective MEK kinase inhibitor of the Ras/Raf/MEK/ERK pathway.Advanced nonsmall-cell lung cancer (NSCLC) patients failing one to two prior regimens underwent KRAS profiling. KRAS wild-type patients were randomized to erlotinib (150 mg daily) or a combination of selumetinib (150 mg daily) with erlotinib (100 mg daily). KRAS mutant patients were randomized to selumetinib (75 mg b.i.d.) or the combination. The primary end points were progression-free survival (PFS) for the KRAS wild-type cohort and objective response rate (ORR) for the KRAS mutant cohort. Biomarker studies of ERK phosphorylation and immune subsets were carried out.From March 2010 to May 2013, 89 patients were screened; 41 KRAS mutant and 38 KRAS wild-type patients were enrolled. Median PFS in the KRAS wild-type arm was 2.4 months [95% confidence interval (CI) 1.3-3.7] for erlotinib alone and 2.1 months (95% CI 1.8-5.1) for the combination. The ORR in the KRAS mutant group was 0% (95% CI 0.0% to 33.6%) for selumetinib alone and 10% (95% CI 2.1% to 26.3%) for the combination. Combination therapy resulted in increased toxicities, requiring dose reductions (56%) and discontinuation (8%). Programmed cell death-1 expression on regulatory T cells (Tregs), Tim-3 on CD8+ T cells and Th17 levels were associated with PFS and overall survival in patients receiving selumetinib.This study failed to show improvement in ORR or PFS with combination therapy of selumetinib and erlotinib over monotherapy in KRAS mutant and KRAS wild-type advanced NSCLC. The association of immune subsets and immune checkpoint receptor expression with selumetinib may warrant further studies.
Gill A.A.,John rtha Cancer Center |
Enewold L.,John rtha Cancer Center |
Zahm S.H.,U.S. National Institutes of Health |
Shriver C.D.,John rtha Cancer Center |
And 5 more authors.
Diseases of the Colon and Rectum | Year: 2014
BACKGROUND: In the general US population, blacks and whites have been shown to undergo colon cancer treatment at disproportionate rates. Accessibility to medical care may be the most important factor influencing differences in colon cancer treatment rates among whites and blacks. OBJECTIVE: We assessed whether racial disparities in colon cancer surgery and chemotherapy existed in an equal-access health care system. In addition, we sought to examine whether racial differences varied according to demographic and tumor characteristics. DESIGN AND SETTING: Database research using the Department of Defense Military Health System. PATIENTS: Patients included 2560 non-Hispanic whites (NHW) and non-Hispanic blacks (NHB) with colon cancer diagnosed from 1998 to 2007. MAIN OUTCOME MEASURES: Logistic regression was used to assess the associations between race and the receipt of colon cancer surgery or chemotherapy while controlling for available potential confounders, both overall and stratified by age at diagnosis, sex, and tumor stage. RESULTS: After multivariate adjustment, the odds of receiving colon cancer surgery or chemotherapy for NHBs versus NHWs were similar (OR, 0.75 [95% CI, 0.37-1.53]; OR, 0.79 [95% CI, 0.59-1.04]). In addition, no effect modifications by age at diagnosis, sex, and tumor stage were observed. LIMITATIONS: Treatment data might not be complete for beneficiaries who also had non-Department of Defense health insurance. CONCLUSIONS: When access to medical care is equal, racial disparities in the provision of colon cancer surgery and chemotherapy were not apparent. Thus, it is possible that the inequalities in access to care play a major role in the racial disparities seen in colon cancer treatment in the general population. © The ASCRS 2014.
Gierach G.L.,U.S. National Cancer Institute |
Pfeiffer R.M.,U.S. National Cancer Institute |
Patel D.A.,U.S. National Cancer Institute |
Black A.,U.S. National Institutes of Health |
And 4 more authors.
Menopause | Year: 2014
OBJECTIVE: As bilateral salpingo-oophorectomy is frequently performed with hysterectomy for nonmalignant conditions, defining health outcomes associated with benign bilateral salpingo-oophorectomy performed at different ages is critical. METHODS: We assessed mortality risk associated with benign total abdominal hysterectomy or bilateral salpingo-oophorectomy among 52,846 Breast Cancer Detection Demonstration Project follow-up study participants. Surgery and risk factor data were ascertained via baseline interview (1979-1986) and three questionnaires (1987-1998). During follow-up through December 2005 (mean, 22.1 y), 13,734 deaths were identified. We estimated hazard ratios (HRs) and 95% CIs for overall and disease-specific mortality for total abdominal hysterectomy or bilateral salpingo-oophorectomy performed by age 35, 40, 45, 50, or 55 years, compared with not having surgery, using landmark analyses and multivariable Cox regression. RESULTS: Undergoing bilateral salpingo-oophorectomy by age 35 years was associated with increased mortality risk (HR35 y, 1.20; 95% CI, 1.08-1.34), which decreased with age (HR40 y, 1.12; 95% CI, 1.04-1.21; HR45 y, 1.10; 95% CI, 1.03-1.17). Total abdominal hysterectomy alone performed by age 40 years was associated with increased mortality risk to a lesser extent (HR40 y, 1.08; 95% CI, 1.01-1.15). Analyses based on matched propensity scores related to having gynecologic surgery yielded similar results. Elevated mortality risks were largely attributable to noncancer causes. CONCLUSIONS: Benign gynecologic surgeries among young women are associated with increased mortality risk, which attenuates with age. © 2014 The North American Menopause Society.
Andaya A.A.,John rtha Cancer Center |
Enewold L.,U.S. National Cancer Institute |
Zahm S.H.,U.S. National Cancer Institute |
Shriver C.D.,John rtha Cancer Center |
And 8 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2013
Studies have shown that Whites have a higher colorectal cancer survival rate than Blacks. However, it is unclear whether racial disparities result from unequal access to medical care or factors other than health care access or both. This study assessed whether non-Hispanic Whites (NHW) and non-Hispanic Blacks (NHB) differ in colon cancer survival in an equal-access health care system and examined whether racial differences varied by demographic and tumor characteristics. The study included 2,537 Military Health System patients diagnosed with colon cancer between 1998 and 2007. Median follow-up time was 31.4 months. Cox models estimated HRs and 95% confidence intervals (CI) for race, overall and stratified by age at diagnosis, sex, and tumor stage. No difference in overall survival (OS) between NHWs and NHBs was observed in general. However, among patients younger than 50 years old, NHBs experienced significantly worse OS than NHWs (HR: 2.03, 95% CI: 1.30-3.19). Furthermore, stratification by sex and tumor stage showed that this racial disparity was confined towomen(HR: 2.87; 95% CI: 1.35-6.11) and patients with distant stage disease (HR: 2.45; 95%CI: 1.15-5.22) in this age group. When medical care is equally available to NHWs and NHBs, similar overall colon cancer survival was observed; however, evidence of racial differences in survival was apparent for patients younger than 50 years old. This study suggests that factors other than access to care may be related to racial disparities in colon cancer survival among younger, but not older, patients. © 2013 American Association for Cancer Research.
PubMed | Uniformed Services University of the Health Sciences, John rtha Cancer Center and U.S. National Cancer Institute
Type: | Journal: Cancer epidemiology | Year: 2016
While the incidence of bladder cancer is twice as high among whites than among blacks, mortality is higher among blacks than whites. Unequal access to medical care may be an important factor. Insufficient access to care could delay cancer detection and treatment, which can result in worse survival. The purpose of this study was to evaluate whether survival differed between black and white bladder cancer patients in the Department of Defense (DoD), which provides universal healthcare to all beneficiaries regardless of racial background.This study was based on data from the U.S. DoD Automated Central Tumor Registry (ACTUR). White and black patients histologically diagnosed with bladder cancer between 1990 and 2004 were included in the study and followed to the end of 2007. The outcomes were all-cause mortality and recurrence. We assessed the relationship between race and outcomes of interest using Cox proportional hazard ratios (HRs) for all, non-muscle invasive (NMIBC), and muscle invasive (MIBC) bladder cancers, separately.The survival of black and white individuals did not differ statistically. No significant racial differences in survival (HR: 0.96, 95% CI: 0.76-1.22) or recurrence-free survival (HR: 0.94, 95% CI: 0.69-1.30) were observed after adjustment for demographic variables, tumor characteristics, and treatment. Similar findings were observed for NMIBC and MIBC patients, respectively.Black patients were more likely to present with MIBC than white patients. However, white and black patients with bladder cancer were not significantly different in overall and recurrence-free survival regardless of muscle invasion. Our study suggests the importance of equal access to healthcare in reducing racial disparities in bladder cancer survival.
Lee S.,The Surgical Center |
Lee S.,John rtha Cancer Center |
Ryu H.,The Surgical Center |
Ryu H.,Hongik Hospital |
And 6 more authors.
Annals of Surgical Oncology | Year: 2014
Background: Minimally invasive parathyroidectomy (MIP) is a targeted operation to cure primary hyperparathyroidism utilizing intraoperative parathyroid hormone monitoring (IOPTH). The purpose of this study was to quantify the operative failure of MIP. Methods: Utilizing institutional parathyroid surgery database, demographic, operative, and biochemical data were analyzed for successful and failed MIP. Operative failure was defined as <6 months of eucalcemia after operation. Results: Five hundred thirty-eight patients (96.6 %) had successful MIP with mean follow-up of 13 months, and 19 (3.4 %) had operative failure. The major cause of operative failure (11 of 19) was the result of surgeons' inability to identify all abnormal parathyroid glands. The remaining eight operative failures were the result of falsely positive IOPTH results. Eleven of 19 patients whose MIP had failed underwent a second parathyroid surgery. All but one of these patients achieved operative success, and 9 patients had missed multigland disease. Only 46 (8.3 %) of 557 patients had conversion to bilateral cervical exploration (BCE). Eighty percent of patients had more than 70 % IOPTH decrease, and all had successful operations. Patients with a marginal IOPTH decrease (50-59 %) had a treatment failure rate of 20 %. Conclusions: The most common cause of operative failure in MIP utilizing IOPTH was the result of surgeons' failure to identify all abnormal parathyroid glands. Falsely positive IOPTH is rare, and a targeted MIP utilizing IOPTH can achieve an excellent operative success rate without routine BCE. Selective BCE on patients with marginal IOPTH decrease may improve surgical outcome. © 2014 Society of Surgical Oncology.
Theeler B.J.,John rtha Cancer Center |
Ellezam B.,University of Montréal |
Sadighi Z.S.,St Jude Childrens Research Hospital |
Mehta V.,Baylor College of Medicine |
And 4 more authors.
Neuro-Oncology | Year: 2014
Background Adult pilocytic astrocytomas (PAs) are rare and have an aggressive clinical course compared with pediatric patients. Constitutive Ras/RAF/MAPK signaling appears to be an important oncogenic event in sporadic PA. We evaluated clinical data and molecular profiles of adult PAs at our institution. Methods We identified 127 adult PAs in our institutional database. Cases with available tissue were tested for BRAF-KIAA1549 fusion/duplication (B-K fusion) by fluorescence in situ hybridization and submitted for mutation profiling using the Sequenom mutation profiling panel. Subgroup analyses were performed based on clinical and molecular data. Results The majority of adult PAs are supratentorial. Twenty-two percent of cases had an initial pathologic diagnosis discordant with the diagnosis made at our institution. Recurrence was seen in 42% of cases, and 13% of patients died during follow-up. Adjuvant radiotherapy following surgical resection was associated with a statistically significant decrease in progression-free survival (P =. 004). B-K fusion was identified in 20% (9 of 45) of patients but was not associated with outcome. No BRAF V600E mutations (0 of 40 tested) were found. Conclusion This was the largest single institution series of adult PA. A significant proportion of adult PAs follow an aggressive clinical course. Our results support a period of observation following biopsy or surgical resection. B-K fusion in adult PA does not influence outcome, and BRAF V600E mutation appears to be a very rare event. Further study of tumor biology and optimal treatment is needed, given a more aggressive clinical behavior. © 2014 The Author(s).
Theeler B.J.,John rtha Cancer Center |
Ellezam B.,University of Montréal |
Yust-Katz S.,University of Houston |
Slopis J.M.,University of Houston |
And 2 more authors.
Journal of Neurology | Year: 2014
Astrocytic tumors, especially optic pathway pilocytic astrocytomas, are common in pediatric NF1 patients. High-grade gliomas (HGGs) appear to be rare in adult and pediatric NF1 patients. This is a series of five consecutive, adult NF1 patients with recurrent HGGs treated at The University of Texas MD Anderson Cancer Center. Four patients met consensus clinical criteria for NF1 and one patient had presumed segmental NF1. Three patients had glioblastomas, one gliosarcoma, and one progressive, enhancing optic pathway glioma which was not biopsied. Two tumors had molecular testing performed; both were IDH wild type and activating oncogene mutations (1 BRAFV600E and 1 PIK3CA mutation) were found in these tumors. All five patients received bevacizumab-containing regimens at tumor recurrence. The median number of 4-week cycles of bevacizumab was 20. All five patients experienced prolonged post-recurrence survival following bevacizumab treatment ranging from ten to 72 months. The median overall survival from HGG diagnosis was 72.6 months with three patients alive and progression free at last follow-up. Three out of five patients developed vascular complications leading to bevacizumab discontinuation. In this case series, adult NF1 patients with recurrent HGGs had prolonged, post-recurrence survival after treatment with bevacizumab-containing regimens. Based on these results, further study of antiangiogenic therapy in NF1 patients with HGGs and bevacizumab-response in sporadic HGG patients with NF1-mutated tumors is warranted. © 2014 Springer-Verlag Berlin Heidelberg.
Donahue T.F.,John rtha Cancer Center |
Cha E.K.,Sloan Kettering Cancer Center |
Bochner B.H.,Sloan Kettering Cancer Center
Current Urology Reports | Year: 2016
Parastomal hernias (PH) represent a clinically significant problem for many patients after radical cystectomy and ileal conduit diversion. The prevalence may be as high as 60 % and in some series, up to 30 % of patients require surgical intervention due to the complications of pain, poor fit of an ostomy appliance, leakage, urinary obstruction, and bowel obstruction or strangulation. Due to the potential morbidity associated with PH repair, there have been efforts to prevent PH development at the time of the index surgery. Four randomized trials of prophylactic mesh placement at the time of colostomy and ileostomy stoma formation have demonstrated significant reductions in PH rates with acceptably low complication rates. In this review, we describe the clinical and radiographic definitions of PH, the clinical impact and risk factors behind its development, and the rationale behind prophylactic mesh placement for patients undergoing ileal conduit urinary diversion. Additionally, we report our experience with prophylactic mesh placed at radical cystectomy at our institution. © 2016, Springer Science+Business Media New York.
PubMed | National Cancer Institute and John rtha Cancer Center
Type: Journal Article | Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | Year: 2016
Higher cancer-related mortality has been observed among people with mental health disorders than in the general population. Both delay in diagnosis and inadequate treatment due to health care access have been found to explain the higher mortality. The U.S. Military Health System (MHS), in which all beneficiaries have equal access to health care, provides an ideal system to study this disparity where there are no or minimal barriers to health care access. This study assessed preexisting mental health disorders and stage at diagnosis, receipt of cancer treatment, and overall survival among patients with non-small cell lung cancer (NSCLC) in the U.S. MHS.The study used data from the linked database from the Department of Defenses Central Cancer Registry and the MHS Data Repository (MDR). The study subjects included 5,054 patients with histologically confirmed primary NSCLC diagnosed between 1998 and 2007.Patients with a preexisting mental disorder did not present with more advanced disease at diagnosis than those without. There were no significant differences in receiving cancer treatments between the two groups. However, patients with a mental health disorder had a higher mortality than those without [adjusted HR, 1.11; 95% confidence interval (CI), 1.03-1.20].Poor survival in NSCLC in patients with a preexisting mental health disorder is not necessarily associated with delay in diagnosis and/or inadequate cancer treatment.This study contributes to the current understanding that health care access may not be sufficient to explain the poor survival among patients with NSCLC with preexisting mental health disorders. Cancer Epidemiol Biomarkers Prev; 25(12); 1564-71. 2016 AACR.