Impact of margin status on survival after radical nephrectomy for renal cell carcinoma.

BACKGROUND: Data about the impact of surgical margin positivity on patient outcomes following radical nephrectomy (RN) for renal cell carcinoma (RCC) is limited. We evaluate the effect of positive surgical margins (PSMs) on relapse-free survival (RFS) and overall survival (OS.) METHODS: Clinicopathologic data of patients who underwent RN for RCC was analyzed based on margin status. χ2 and Student t test were used to compare groups. Cox regression analysis was used for the analysis. Kaplan-Meier method was used for survival curves. RESULTS: A total of 485 patients who underwent RN for RCC were analyzed. Most patients with T1/T2 stage had NSM. Most patients with T4 had PSM. T3 patients were split between the two groups. Analysis of the T3 group showed shorter RFS in the PSM group at 3 years (hazard ratio [HR]: 4.3, p = .01), and 5 years (HR: 4.3, p = .01.) OS analysis showed worse OS in PSM but not statistically significant. There was a significant association between PSM and laterality (p = .023) and histologic type (p = .025.) CONCLUSIONS: PSM was associated with shorter RFS after RN in T3 RCC patients. There was a trend towards worse OS in the PSM group, but it did not reach statistical significance. Laterality and histologic type were associated with surgical margin status.

Next-Generation Sequencing and In Silico Analysis Facilitate Prolonged Response to Pazopanib in a Patient With Metastatic Urothelial Carcinoma of the Renal Pelvis.

With the advent of widespread tumor genetic profiling, an increased number of mutations with unknown significance are being identified. Often, a glut of uninterpretable findings may confuse the clinician and provide little or inappropriate guidance in therapeutic decision-making. This report describes a method of protein modeling by in silico analysis (ie, using computer simulation) that is easily accessible to the practicing clinician without need for further laboratory analysis, which can potentially serve as a guide in therapeutic decisions based on poorly characterized tumor mutations. An example of this model is given wherein poorly characterized KIT, PDGFRB, and ERBB2 mutations were discovered in a patient with treatment-refractory metastatic transitional cell carcinoma of the renal pelvis. The KIT and PDGFRB mutations were predicted to be pathogenic using in silico analysis, whereas the ERBB2 mutation was predicted to be benign. Based on these findings, the patient was treated with pazopanib and achieved a partial response that lasted for 7.5 months. We propose that in silico analysis be explored as a potential means to further characterize genetic abnormalities found by tumor profiling assays, such as next-generation sequencing.

Mortality, length of stay, and health care costs of febrile neutropenia-related hospitalizations among patients with breast cancer in the United States.

PURPOSE: Febrile neutropenia is a potentially life threatening complication of breast cancer chemotherapy associated with a significant amount of morbidity, mortality, and health care resource utilization. Recent data on the national estimates of mortality rate, length of stay, and health care costs among the subpopulation of febrile neutropenia admissions with breast cancer are lacking. METHODS: We used the Nationwide Inpatient Sample database to identify patients with breast cancer hospitalized for febrile neutropenia from 2009 to 2011. We derived data on inhospital mortality rate, length of stay, and mean health care costs and compared it with previous studies. RESULTS: The average inhospital mortality rate during 2009-2011 was 2.6 % (n = 685). Advanced age (≥ 65 years) was found to be significantly associated with a higher odds of mortality (4.4 vs 1.7 %, OR 2.7, 95 % CI 2.3-3.1, p < 0.01). The mean length of stay was 5.7 days (95 % CI 5.5-5.9 days), whereas the mean cost of hospitalization was $37,087 (95 % CI $34,009-$40,165). CONCLUSION: Febrile neutropenia-related hospitalizations continue to account for significant morbidity, mortality, and health care resource utilization among patients with breast cancer. Further efforts should be focused on curtailing the rising health care costs without compromising the quality of care.

Personalized Medicine in Oncology in the Developing World: Barriers and Concepts to Improve Status Quo.

Personalized medicine (PM) has revolutionized oncology management in high human development indexed countries. By interrogating both disease and host factors through a variety of tools, oncologists have been able to better target an individual's cancer, leading to improved outcomes. But both the tools used to define these variables, such as next generation sequencing, large immunohistochemical and fluorescence in situ hybridization (FISH) panels, and the weapons employed against each target are extremely expensive. The expenses have to be measured as not only the direct cost to the patient but also the cost to the system to develop and deploy the necessary infrastructure to optimally use them. However, the concepts of predictive, timely prevention and PM have demonstrated improvement in patient's satisfaction and cost effectiveness. In this paper we will summarize the relevant barriers and challenges that limit the implementation of PM in the developing world with an emphasis on the challenges in Nigeria and Nepal.

Association Between Pesticide Use and Incidence of Diffuse Large B-Cell Lymphoma.

BACKGROUND/AIM: Exposure to pesticides has been reportedly associated with several types of cancer. MATERIALS AND METHODS: In this study, we used data from The United States Geological Survey (USGS), United States Census, and the Surveillance, Epidemiology, and End Results (SEER) database to analyze the association between the area density of specific agricultural pesticides and the county level annual incidence of diffuse large B-cell lymphoma (DLBCL). RESULTS: Incidence of DLBCL was significantly associated with an area density of 14 of the pesticides reported by USGS. CONCLUSION: This highlights the need for further investigation into the safety of the use of these pesticides. The importance of this study comes not only from the significant association it shows between pesticides and the incidence of cancer, but also from the fact that it included all compounds reported to USGS as being used in agriculture. This helps in prioritizing pesticides for further evaluation.

Distribution of Breast Cancer Subtypes Among Nigerian Women and Correlation to the Risk Factors and Clinicopathological Characteristics.

BACKGROUND: Breast cancer in African women differs from the Caucasian. Understanding the profile of Nigerian women with breast cancer will help with preventive measures and treatment. This study focused on the clinico-pathological characteristics, with risk factors of breast cancer patients in Nigeria. METHODS: Newly diagnosed female patients with breast cancer were assessed over 12 months. Patients were reviewed using a predesigned proforma which focused on socio-demographic information, clinical information, risk factors and tumor biology. RESULTS: A total of 251 women were identified; their mean age was 46 years. More than half (62.5%) are premenopausal at presentation, 37.8% with Eastern Cooperative Oncology Group (ECOG) score of 0 and right side (50.2%) as the most common primary site of disease. Less than half of them (43.0%) are estrogen receptor (ER) positive, 27.9% are progesterone receptor (PR) positive, 43.8% and 47.4% are hormone receptor positive and triple negative, respectively. Most patients presented at the latter stage of the disease, stage III (66.9%) and stage IV (18.3%). Only 15.9% are well differentiated and almost all (92.8%) had invasive ductal histological type. Obesity (66.2%) and physical inactivity (41.9%) are the most common risk factors for the disease. A significant relationship was found between immunohistochemistry status and family history of breast cancer, tumor site, previous breast surgery, previous lump and alcohol intake. CONCLUSION: Findings from this study showed that Nigerian breast cancer patients differ from their counterparts in the high human development index (H-HDI) countries in terms of the patients and disease characteristics. In view of this, prevention and treatment options should consider this uniqueness to ensure better outcome.

Therapy related acute myeloid leukemia in breast cancer survivors, a population-based study.

The aim of this study was to determine the association between age and stage at diagnosis of breast cancer with the subsequent development of acute myeloid leukemia (AML). The National Cancer Institute's Surveillance, Epidemiology, and End Results program were analyzed for incidence of second malignancies by age and stage at diagnosis of breast cancer. 420,076 female patients were identified. There was an age dependent risk of a subsequent diagnosis of AML in women younger than 50 years old (RR 4.14; P < 0.001) and women 50-64 years old (RR 2.19; P < 0.001), but not those 65 and older (RR 1.19; P = 0.123) when compared with the expected incidence of AML. A similar age dependent pattern was observed for second breast and ovarian cancers. There was also a stage dependent increase in risk of subsequent AML in younger women with stage III disease when compared with stage I disease (RR 2.92; P = 0.004), and to a lesser extent in middle age women (RR 2.24; P = 0.029), but not in older women (RR 0.79; P = 0.80).Younger age and stage III disease at the time of breast cancer diagnosis are associated with increased risk of a subsequent diagnosis of AML. This association maybe explained by either greater chemotherapy exposure or an interaction between therapy and genetic predisposition.

A phase II study of 5-day intravenous azacitidine in patients with myelodysplastic syndromes.

The approved 7-day schedule of subcutaneous azacitidine for myelodysplastic syndrome is associated with injection site reactions and bruising and may be inconvenient because of the need for weekend doses. Although pharmacokinetic data with IV azacitidine suggests equivalence, there are no efficacy data published. Patients with all myelodysplastic syndromes (MDS) FAB subtypes were enrolled and received 75 mg/m(2)/d of azacitidine by 20-min intravenous infusion for 5 days in every 28 days. Global methylation studies were performed at baseline and prior to Cycle 3. Twenty-five patients were enrolled and 22 were evaluable. Median age was 69.5 years; 9 (41%) patients had lower-risk disease (IPSS Low or Int-1) and 13 (59%) had higher-risk disease (IPSS Int-2 or High). Twenty-seven percent of patients responded (5 CRs and 1 PR). The median time to response was 108 days. The median PFS was 339 days (11.3 months), the median OS was 444 days (14.8 months) and the median duration of response (DOR) was 450 days (15.0 months). Global methylation studies suggest a greater degree of demethylation in responders. This regimen appeared to offer a PR + CR rate and median DOR somewhat similar to what has been reported with the 7-day subcutaneous regimen; however, OS was shorter.

Salvage therapy for acute myeloid leukemia with fludarabine, cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G-CSF.

The current salvage therapies for relapsed/refractory acute myeloid leukemia (AML) are unsatisfactory. Over the past 7 years, we have used two salvage regimens: fludarabine, cytarabine, and idarubicin with (FLAG-IM) or without gemtuzumab ozogamicin (GO) (9 mg/m(2) on Day 8) (FLAG-I) in relapsed/refractory AML. Three-quarters of patients also received concurrent G-CSF. Seventy-one patients were treated, 23 with FLAG-I and 48 with FLAG-IM. The median duration of follow-up was 30.6 months. The treatment groups were well balanced with median ages of 48 years (range 18-70) and 47 years (range 20-68), unfavorable cytogenetics in 57% and 35%, prior allogeneic stem cell transplant in 43% and 42%, and CR1 duration <1 year in 60% and 67%, respectively, for FLAG-I and FLAG-IM. The complete remission (CR) rate in the FLAG-I group was 39% with an additional 13% achieving a CRp [overall response rate (ORR) 52%]; the CR rate in the FLAG-IM group was 29% with an additional 27% achieving a CRp (ORR 56%). The median duration of response (DOR; 16.8 vs. 8.3 months), event-free survival (EFS; 7.4 vs. 4.1 months), and overall survival (OS; 8.8 vs. 5.0 months) trended to favor FLAG-I over FLAG-IM. The patients who received G-CSF concurrent with chemotherapy had superior overall response rate (ORR; 62% vs. 29%, P = 0.026), median EFS (6.2 vs. 3.4 months, P = 0.010), and OS (8.8 vs. 3.9 months, P = 0.004) when compared with those who sequentially received G-CSF and chemotherapy, regardless of chemotherapy regimen. The addition of GO, at this dose and schedule, to FLAG-I failed to improve the outcomes in patients with relapsed/refractory AML. The patients who received G-CSF concurrently with chemotherapy had improved outcomes. Am. J. Hematol., 2009. (c) 2009 Wiley-Liss, Inc.

Molecular Alterations Associated with DNA Repair in Pancreatic Adenocarcinoma Are Associated with Sites of Recurrence.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies with a rising incidence. Mutational analysis of PDAC has provided valuable information but has not yet dramatically changed the therapeutic landscape due to the number of variations detected in any one individual. The pattern of molecular alterations-gene mutations, variations in copy number, and changes in gene expression-has been described in the literature. The purpose of this study is to further investigate the molecular alterations in recurrent or metastatic PDAC based on the site of disease. METHODS: Molecular alterations in patients with recurrent or metastatic PDAC from 2007 to 2015 were analyzed. The most common molecular alterations found in PDAC tumors from the pancreas were compared to metastatic PDAC specimens from the liver, lung, peritoneum, and other locations. Means were compared with a two-tailed Student's t test or ANOVA as appropriate. Rates of molecular alterations among the different groups were compared with Pearson's χ2. RESULTS: Two thousand five hundred fifty-two patients with PDAC were identified in a retrospective database, and the 15 most common molecular alterations were utilized for analysis. The most common alterations among all patients were mutations in KRAS and PTEN (59 and 62%, respectively), with differences in prevalence by site of metastasis (p = 0.042 and p = 0.037, respectively). KRAS mutations were more commonly found in metastasis in the lung (72%) than in other sites (59%, p = 0.042). Low expression of ERCC1 was found in 49% of lung metastases from PDAC but only 15% in PDAC in the pancreas (p < 0.001). Five of the 8 molecular alterations significantly associated with site of metastatic disease were involved in DNA maintenance, repair, replication, or transcription (each p < 0.001). CONCLUSIONS: Aberrant expression or mutation in genes involved in DNA maintenance is found in association with specific sites of metastatic PDAC. Personalizing therapy for metastatic PDAC based on site of disease and their associated molecular alterations warrants further investigation.