Determinants of ten-year overall survival of acute myeloid leukemia: a large national cancer database analysis.

Clinical trials do not routinely capture long-term overall survival (OS) in acute myeloid leukemia (AML). We utilized a large National Cancer Database (NCDB) to determine different factors affecting 10-year OS in AML. For patients, 18-59 years who were treated with chemotherapy only without upfront hematopoietic cell transplant (HCT), younger age, female, CBF AML, higher income, and private insurance conferred higher 10-year OS. Among patients, 18-59 years treated with chemotherapy and upfront HCT, younger age and private insurance conferred higher 10-year OS. In a Cox proportional hazard model, the likelihood of death decreased with younger age, fewer comorbidities, treatment at an academic center, private insurance, and use of multiagent chemotherapy. Our results demonstrate poor long-term OS even among younger patients and highlights disparities in leukemia care based on insurance type.

Multimodality Therapy for Limited-Stage Small-Cell Lung Cancer.

Limited-stage small-cell lung cancer (SCLC) occurs in only one third of patients with SCLC, but it is potentially curable. Combined-modality therapy (chemotherapy and radiotherapy) has long been the mainstay of therapy for this condition, but more recent data suggest a role for surgery in early-stage disease. Prophylactic cranial irradiation seems to improve outcomes in patients who have responded to initial therapy. This review addresses the practical aspects of staging and treatment of patients with limited-stage SCLC.

Clinicopathologic characteristics and management trends of cutaneous invasive and in situ melanoma in older patients: a retrospective analysis of the National Cancer Data Base.

BACKGROUND: The incidence of melanoma in older patients is on the rise. Prior studies have shown disparities in surgical management and poor survival of older patients with melanoma. METHODS: This is a retrospective study of adult patients diagnosed with cutaneous invasive and in situ melanoma between 2000 and 2011 in the National Cancer Data Base. Characteristics and management of older patients (≥60 years) were compared with younger patients (20-59 years) using χ(2) testing. RESULTS: Of 476,623 total cases, 54% (n = 258,153) were diagnosed among older patients. The reported cases in the older patients increased by 1.74-fold between 2000 and 2011. The majority were white (96%), men (65%), with early-stage disease (76% stage 0-II), and superficial spreading melanoma histology (39%). Older patients, compared with younger patients, were more likely to be men (65% versus 49%, p < 0.0001), and have in situ melanoma (28% versus 21%, p < 0.0001); less likely to have nodal metastases (7% versus 9%, p < 0.0001), receive care in academic centers (30% versus 35%, p < 0.0001), undergo wide excision or major amputation for stage I-III disease (68% versus 72%, p < 0.0001) and systemic therapy for stage III (18% versus 45%, p < 0.0001) and IV disease (30% versus 50%, p < 0.0001). CONCLUSION: Older patients with melanoma are less likely to receive care in academic centers, undergo wide excision for stage I-III disease and receive systemic therapy for stage III-IV disease. Particularly, the utilization of systemic therapy is markedly low. This disparity is particularly important with the availability of less intense more effective therapies.

A retrospective analysis of reported errata in five leading medical journals in 2012.

BACKGROUND: Although medical publications are frequently used as the source of information, the prevalence of errata remains unclear. The objective of this study was to examine peer-review and publication processes of medical journals as well as to determine the occurrence of reported errata in medical journals and timeliness in identifying and correcting errata. METHODS: Five medical journals, New England Journal of Medicine, Annals of Internal Medicine, British Medical Journal, Journal of American Medical Association, and Lancet, were evaluated. The characteristics of these journals were obtained from editors' survey. All these journals report errata noted in their prior publications. We retrospectively analyzed all errata reported from January 1, 2012, to December 31, 2012. The mean number of reported errata per issue, the most common errata, and the mean time to report errata were calculated. RESULTS: The journals had high impact factors (14-51), received 3,200 to more than 15,000 submissions in 2012, and utilized two or more external reviewers and usually two or more editors for any accepted articles. All the journals edited the accepted articles, including references, figures, and tables for style. A mean of 1.3 articles with ≥1 errata was reported per issue (a total of 306 articles with errata in 226 issues). Errata in author's information, numeric errata, and errata in the figures and tables were the most common errata. The mean time to report the errata was 122 days. CONCLUSION: The high-impact journals, with extensive pre-publication review, reported relatively few errata per issue. The delay in reporting errata needs further exploration.

Cyclooxygenase-2 expression in non-metastatic triple-negative breast cancer patients.

Triple-negative breast cancer (TNBC) is characterised by lack of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER)2/neu gene amplification. TNBC patients typically present at a younger age, with a larger average tumor size, higher grade and higher rates of lymph node positivity compared to patients with ER/PR-positive tumors. Cyclooxygenase (COX)-2 regulates the production of prostaglandins and is overexpressed in a variety of solid tumors. In breast cancer, the overexpression of COX-2 is associated with indicators of poor prognosis, such as lymph node metastasis, poor differentiation and large tumor size. Since both TNBC status and COX-2 overexpression are known poor prognostic markers in primary breast cancer, we hypothesized that the COX-2 protein is overexpressed in the primary tumors of TNBC patients. The purpose of this study was to determine whether there exists an association between TNBC status and COX-2 protein overexpression in primary breast cancer. We prospectively evaluated COX-2 expression levels in primary tumor samples obtained from 125 patients with stage I-III breast cancer treated between February, 2005 and October, 2007. Information on clinicopathological factors was obtained from a prospective database. Baseline tumor characteristics and patient demographics were compared between TNBC and non-TNBC patients using the Chi-square and Fisher's exact tests. In total, 60.8% of the patients were classified as having ER-positive tumors, 51.2% were PR-positive, 14.4% had HER-2/neu amplification and 28.0% were classified as TNBC. COX-2 overexpression was found in 33.0% of the patients. TNBC was associated with COX-2 overexpression (P=0.009), PR expression (P=0.048) and high tumor grade (P=0.001). After adjusting for age, menopausal status, body mass index (BMI), lymph node status and neoadjuvant chemotherapy (NACT), TNBC was an independent predictor of COX-2 overexpression (P=0.01). In conclusion, the association between TNBC and COX-2 overexpression in operable breast cancer supports further investigation into COX-2-targeted therapy for patients with TNBC.

Outpatient management of heart failure in the United States, 2006-2008.

Better outpatient management of heart failure might improve outcomes and reduce the number of rehospitalizations. This study describes recent outpatient heart-failure management in the United States. We analyzed data from the National Ambulatory Medical Care Survey of 2006-2008, a multistage random sampling of non-Federal physician offices and hospital outpatient departments. Annually, 1.7% of all outpatient visits were for heart failure (51% females and 77% non-Hispanic whites; mean age, 73 ± 0.5 yr). Typical comorbidities were hypertension (62%), hyperlipidemia (36%), diabetes mellitus (35%), and ischemic heart disease (29%). Body weight and blood pressure were recorded in about 80% of visits, and health education was given in about 40%. The percentage of patients taking ß-blockers was 38%; the percentage taking angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs) was 32%. Medication usage did not differ significantly by race or sex. In multivariate-adjusted logistic regression models, a visit to a cardiologist, hypertension, heart failure as a primary reason for the visit, and a visit duration longer than 15 minutes were positively associated with ACEI/ARB use; and a visit to a cardiologist, heart failure as a primary reason for the visit, the presence of ischemic heart disease, and visit duration longer than 15 minutes were positively associated with ß-blocker use. Chronic obstructive pulmonary disease was negatively associated with ß-blocker use. Approximately 1% of heart-failure visits resulted in hospitalization. In outpatient heart-failure management, gaps that might warrant attention include suboptimal health education and low usage rates of medications, specifically ACEI/ARBs and ß-blockers.

Angioimmunoblastic T-cell lymphoma management.

Angioimmunoblastic T-cell lymphoma (AITL) is a frequent subtype of peripheral T-cell lymphoma (PTCL) that is clinically characterized by generalized lymphadenopathy, extranodal involvement, advanced stage at presentation, hypergammaglobulinemia, and significant immune dysregulation resulting in infections as the most common cause of death. Recent advances in pathobiology of AITL have improved our understanding of it as a clonal T-cell disorder and of its effect on B cells in the tumor microenvironment. Reponses to first-line therapies have largely been dismal. In this review, we discuss the clinical features, pathobiology, prognostic models, standard therapy, and newer therapeutic agents used and their implications for the future.

Disseminated tumor cells in biologic subtypes of stage I-III breast cancer patients.

BACKGROUND: Triple receptor-negative breast cancers (TNBC) are higher grade and more likely to metastasize. Recurrences after 5 years are rare in TNBCs. Conversely, late recurrences are seen in estrogen receptor (ER)-positive (luminal) cancers. Disseminated tumor cells (DTCs) may be responsible for late recurrences. We compared rates of DTCs in basal and luminal subtypes. METHODS: We evaluated 205 stage I-III patients. DTCs were assessed from bone marrow aspirates using anti-cytokeratin (CK) antibody following cytospin, and the presence of ≥ 1 CK-positive cells was considered positive. Pathologic complete response (pCR) was defined as lack of invasive disease in primary tumor and regional lymph nodes after neoadjuvant chemotherapy (NAC). Statistical analyses used chi-square and Fischer's exact test. RESULTS: Median follow-up (f/u) was 27 months, and 40% of patients had NAC. Forty patients had TNBC, and 148 had luminal cancers. Seventeen percent of TNBC patients, and 27% of those with luminal subtype, had DTCs after NAC (P = NS). Following NAC, pCR occurred in 28% of TNBC and 23% of luminal patients. Luminal A subtypes were less likely to achieve pCR when compared with non-luminal A subtypes (16 versus 41%; P = 0.01). All TNBC patients who achieved pCR had complete eradication of DTCs, whereas 36% of luminal (A and B) subtypes had DTCs. CONCLUSIONS: DTCs were found in 29% of stage I-III patients. TNBCs were more likely to have complete eradication of DTCs after pCR. Further study is needed to determine whether DTCs are responsible for late recurrences in patients with luminal cancers.

Evaluation of a CXCR4 antagonist in a xenograft mouse model of inflammatory breast cancer.

CXCL12/CXCR4 signaling, being important in the homing of cancer cells to lungs, bone and other organs, is a promising therapeutic target. Our purpose was to determine whether a peptide-based antagonist of CXCR4 would reduce primary tumor growth and/or metastasis in a preclinical mouse model of inflammatory breast cancer. We improved an existing model of inflammatory breast cancer for this study by luciferase transfection of SUM149 cells and the monitoring of such cells in mice by imaging and the luciferase assay. We implanted 2 x 10(6) SUM49-Luc cells along with matrigel into the left thoracic mammary fat pad of nude mice to produce tumors. Our mouse model exhibited important features of inflammatory breast cancer, namely, aggressive local disease, local metastases and distant metastases. To evaluate the efficacy of a CXCR4 antagonist CTCE-9908, by itself or in combination with paclitaxel, we treated groups of ten mice each with CTCE-9908 (25 mg/kg, injected subcutaneously 5 days/week), control peptide SC-9908, paclitaxel (10 mg/kg, injected subcutaneously twice a week), and CTCE-9908 plus paclitaxel concurrently. We assessed all mice weekly by whole-body luciferase imaging to quantify relative primary tumor burden and distant metastases. At the end of the experiment, we quantified primary tumors by weight and lung metastases by luciferase activity assay on tissue lysates. Paclitaxel, a known chemotherapeutic, inhibited primary tumor growth in our model (P < 0.05). CTCE-9908 did not significantly inhibit primary tumor growth or lung metastases as compared to control groups, without or with paclitaxel (P > 0.05). However, CTCE-9908 as a single therapy inhibited organ-specific metastasis to leg (P < 0.05 by chi-squared test and by two-sample t-test).

HER2 status predicts the presence of circulating tumor cells in patients with operable breast cancer.

INTRODUCTION: Circulating tumor cells (CTCs) correlate with worse prognosis in patients with metastatic breast cancer, but there are little data on CTCs in operable patients. We hypothesized that primary tumor characteristics would predict the likelihood of identifying CTCs in patients with operable breast cancer. METHODS: Clinical and pathological data from 92 patients with operable breast cancer were collected. The CellSearch system was used to detect CTCs in 30 ml of peripheral blood. CTCs were defined as nucleated cells lacking CD45 but expressing cytokeratins 8, 18, or 19. Univariate analysis was performed to determine if the presence of any primary tumor characteristic was predictive of CTCs. As a secondary objective we evaluated if nodal or bone marrow status was predictive of CTCs. RESULTS: Thirty-eight percent of patients (35/92) had evidence of CTCs, with a median number of 1.0 CTC per CTC positive patient (range 1-22). HER2 status was the sole primary tumor characteristic that reliably predicted the presence of CTCs (P = 0.01, risk ratio = 3.66). No significant association was found between the presence of CTCs and tumor size (T), estrogen receptor (ER) status, progesterone receptor (PR) status, grade, histologic type, degree of nodal involvement (N), lymphovascular invasion (LVI) or Ki-67 proliferation. Bone marrow micrometastases were found in 17/64 (26.6%) of the patients but did not correlate with the presence of CTCs. CONCLUSION: HER2 status was the only primary tumor characteristic that correlated with the presence of CTCs. Long-term follow-up will be required to determine the significance of CTCs in operable breast cancer.

Cyclooxygenase-2 expression in primary breast cancers predicts dissemination of cancer cells to the bone marrow.

PURPOSE: Cyclooxygenase-2 (COX2) plays a role in breast cancer progression at various stages starting from pre-malignant phenotype to clinical metastasis. Breast cancer metastasizes commonly to the bone and preclinical studies suggest an involvement of COX2 in this process. Detection of disseminated tumor cells in the bone marrow of patients at the time of surgery correlates with the subsequent development of clinical bone metastasis. Therefore, to investigate whether COX2 is important for breast cancer metastasis in humans, we analyzed COX2 protein expression by immunostaining of primary tumors from 112 operable stages I, II, or III patients and determined its correlation with bone marrow micrometastasis (BMM). METHODS: We detected COX2 protein in primary tumors by immunostaining with a monoclonal antibody, and tumor cells present in the bone marrow by immunostaining for epithelial cytokeratins and by morphological criteria. RESULTS: COX2 expression in primary breast cancer correlated with BMM in a highly statistically significant manner (P = 0.006). Our statistical analyses of correlations of the COX2 positivity in primary tumor with other clinically relevant indicators revealed that COX2 positivity correlates with high nuclear grade (P = 0.0004). Furthermore, we were able to detect COX2 protein in BMM by immunostaining. CONCLUSIONS: These studies indicate that COX2 produced in primary breast cancer cells may be vital to the initial development of BMM that may subsequently lead to osteolytic bone metastases in patients with breast cancer, and that COX2 inhibitors may be useful in halting this process.