An investigation of neuropsychiatric symptoms, contextual factors, and antidepressant treatment as risk factors for dementia development in people with mild cognitive impairment.

BACKGROUND: While some people with mild cognitive impairment (MCI) progress to dementia, many others show no progression. The aim of this study was to identify factors associated with risk of dementia development in this population. METHOD: A large naturalistic retrospective cohort study was assembled from mental healthcare records in a south London catchment. Patients were selected at first recorded diagnosis of MCI and subsequent dementia diagnosis was ascertained from case notes or death certificate, excluding those with dementia diagnoses and deaths within 6 months of MCI diagnosis. A range of demographic and clinical characteristics were ascertained around MCI diagnosis and Cox proportional hazards models were used to investigate independent predictors of dementia, focussing on neuropsychiatric symptoms, contextual factors, and antidepressant treatment. RESULTS: Of 2250 patients with MCI, 236 (10.5%) developed dementia at least 6 months after MCI diagnosis. Aside from older age, lower cognitive function, and activities of daily living impairment, impaired social relationships and recorded loneliness were associated with a higher risk of developing dementia. Patients of Black (compared to White) ethnicity were at a lower risk. For depression and antidepressant receipt, only tricyclic use compared to no antidepressant use was associated with an increased dementia risk. CONCLUSIONS: No evidence was found for co-morbid affective disorders or different antidepressant classes as risk factors for dementia development following MCI diagnosis, but loneliness and social impairment were independent predictors and would be worth evaluating as targets for interventions to delay progression.

Predictors of Extracapsular Extension in Patients With Squamous Cell Carcinoma of the Head and Neck and Outcome Analysis.

Introduction Extracapsular extension (ECE) in the lymph nodes for patients with head and neck cancer has been found to be a poor prognostic factor in multiple studies. The purpose of the study is to evaluate the predictive factors for ECE on computer tomography (CT) imaging for patients undergoing surgery and to analyze outcomes. Methods We conducted an Institutional Review Board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective review of 82 patients with biopsy-proven squamous cell carcinomas of the head and neck who underwent definitive surgery without neoadjuvant chemotherapy or radiation therapy. CT scans were evaluated for the level of involvement, size, and presence or absence of central necrosis. Extracapsular extension in lymph nodes on the postoperative pathology was correlated with the central necrosis in the lymph nodes appreciated on the CT neck with contrast. Survival estimates were evaluated using the Kaplan-Meier test. Results ECE on postoperative pathology was seen in 74.07% of patients who had evidence of central necrosis in lymph nodes on preoperative CT neck compared to 46.43% without CT necrosis (p=0.013). The incidence of ECE is higher in poorly differentiated tumors and also nodal stages >N2c at presentation. Patents with ECE had inferior disease-free and overall survival (OS). Conclusions Our results reveal that patients with necrosis on CT and with moderately to poorly differentiated tumors have a high incidence of extracapsular extension. There was no difference in local control (LC) between the groups of patients, but the OS was inferior in patients with ECE. Predicting extracapsular extension upfront helps to formulate the appropriate treatment. We propose to study additional chemotherapy to improve outcomes in patients with positive extracapsular extension.

Small Cell Carcinoma of the Prostate: A Case Report and Review of the Literature.

Small cell carcinoma of the prostate (SCCP) is a rare malignancy that is considered a lethal entity of prostate cancer. Once it is diagnosed, patients characteristically experience an aggressive clinical course with poor overall survival rates, which unfortunately still holds even with modern treatments. In this report, we discuss the case of a 63-year-old African American male who initially presented to the hospital with an elevated prostate-specific antigen (PSA) level of 9.41 ng/mL and was found to have locally extensive SCCP. After one cycle of chemotherapy, the patient's symptoms worsened, and his disease continued to progress with an increased metastatic burden. In a matter of just a few months, the patient's disease progressed from a locally advanced entity to a diffusely metastatic one, showcasing the true aggressive nature of this disease. Through an extensive literature review, this case report also sheds further light on SCCP's histological characteristics, its apparent differences from adenocarcinoma of the prostate, and its aggressive nature even through treatment.

Prostate Cancer Screening Guidelines for African American Veterans: A New Perspective.

BACKGROUND: Prostate cancer is the most common form of cancer, other than skin cancers, in American men and the second leading cause of cancer deaths. In 2012, the US Preventative Task Force recommended against the prostate specific antigen-based screening for prostate cancer, regardless of race or age, due to overtreatment of low-risk disease and lack of impact on disease outcomes. In African-American men, however, the incidence of prostate cancer is almost 60% higher and the mortality rate is two- to three-times greater than that of Caucasian men. In the subpopulation of African-American veterans, many have been exposed to chemicals that increase incidence of high-risk prostate cancer. The yearly total number of veterans with prostate cancer based on quantification is 3471.9, and the total number of annual prostate cancer deaths is 556. Considering these facts, we examine whether or not it is appropriate to screen African-American veteran males for prostate cancer. Previously, we reviewed data on African-Americans in the general population. We concluded that new guidelines needed to be implemented for screening African-Americans. Here we review the pertinent issues related to African-American veterans. METHODS: We performed a PubMed and Google Scholar search using the keywords: African-American veteran, prostate cancer, mortality, PSA density, molecular markers, and Agent Orange. The articles that were relevant to the clinical, molecular, social, and health policy aspects of the diagnosis and treatment of prostate cancer in African-American veterans were analyzed. The data was then summarized. RESULTS: After surveying the literature, we found several areas where the African-American veteran population differed from their Caucasian counterparts. These areas were incidence, clinical course, social differences, PSA levels, mortality rate, and molecular markers. A subset of the veteran population was also exposed to Agent Orange, which has been shown to increase the incidence of aggressive forms of prostate cancer. Lastly, the current USPTF guidelines recommending against prostate cancer screening were based on patient cohorts containing disproportionately low numbers of African-Americans, limiting their extension to the African-American veteran population. CONCLUSION: After reviewing and summarizing the literature, we contend that a need exists to develop and implement more targeted prostate cancer screening guidelines for African-American veterans.

Racial disparities in tumor features and outcomes of patients with squamous cell carcinoma of the tonsil.

OBJECTIVE: To identify differences in 3-year overall survival (OS) and disease-free survival (DFS) based on race in patients with tonsillar squamous cell carcinoma. METHODS: We retrospectively analyzed 80 patients with squamous cell carcinoma of the tonsil treated between 2006 and 2015. Overall survival and DFS curves comparing white and black patients were generated using the Kaplan-Meier method. Cox regression was used to determine covariables associated with OS and DFS. RESULTS: Forty-one percent of the patients in this cohort were black and 59% were white. Three-year OS for black patients was 45.5% versus 88.1% for white patients (P = 0.003). Three-year DFS for black patients was 41.1% versus 66.6% in white patients (P = 0.001). Black race (hazard ratio [HR] 4.81, 95% confidence interval [CI] 1.48-15.6, P = 0.009) and lack of insurance (HR 9.50, 95% CI 2.92-13.0, P < 0.009) were independently associated with worse OS on multivariable analysis. Black patients were more likely to have high-risk tumor features. Black patients with stage IV disease (American Joint Committee on Cancer, 7th edition) had decreased OS as compared to white patients, 41.4% versus 82.1% (P = 0.005). There was a trend toward worse OS in human papillomavirus (HPV)-negative black patients compared to HPV-negative white patients. Uninsured black patient experienced worse OS than white patients without insurance, 22.2% versus 68.1%, respectively (P < 0.001). CONCLUSION: Significant racial disparities were found in presentation, tumor, and nodal characteristics, as well as in outcomes in this group of patients with tonsillar cancer. The difference in HPV-associated tonsillar cancer is likely the primary cause of these disparities, but other factors may also contribute to inferior outcomes in black patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 129:643-654, 2019.

Outcomes utilizing intensity-modulated radiotherapy in oropharyngeal cancers: Tonsils versus base of tongue.

BACKGROUND: The purpose of this study was to present the outcomes of oropharyngeal cancers treated with intensity-modulated radiotherapy (IMRT) especially the differences between tonsillar and base of tongue (BOT) primaries. METHODS: Retrospective analysis of 124 patients with biopsy proven squamous cell carcinomas of the oropharynx, treated with IMRT. RESULTS: Human papillomavirus (HPV) association correlated with improvement in survivals in both tonsillar and BOT primaries. At the 2-year median follow-up, the cumulative incidences of locoregional recurrences were 8% in both the tonsil and BOT groups (P = .76) but the distant metastases were 8% in the tonsil group versus 26% in the BOT group (P = .009). Thirty percent of tonsil primaries has ≥N2c neck disease as compared to 54% of BOT. Incidence of distant metastases increases with advanced nodal classification, especially >N2c. CONCLUSION: Even though the locoregional controls are excellent with IMRT and chemotherapy, these patients continue to fail distantly, particularly significant for the BOT group and for nodal stage >N2c.

Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer: A Retrospective, Single-Center Study of 55 Patients.

Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) is an effective treatment for patients with early-stage non-small cell lung cancer (NSCLC) who are not surgical candidates or who refuse surgical management. In this study, we report on our clinical outcomes and toxicity in the treatment of early-stage NSCLC with SBRT. METHODS AND MATERIALS: Fifty-five patients with 59 T1-2N0M0 NSCLC lesions were treated at our institution between December 2009 and August 2014. The majority of the patients [38 (69%)] were treated with 50 Gy in 5 fractions, 7 patients (13%) with 48 Gy in 4 fractions, 8 patients (14%) with 60 Gy in 3 fractions, 1 patient (2%) with 62.5 Gy in 10 fractions, and 1 patient (2%) with 54 Gy in 3 fractions. Tumor response was evaluated using RECIST 1.1, and toxicity was graded using the CTCAE (Common Terminology Criteria for Adverse Events) version 3.0. The primary endpoints of this retrospective review included rates of overall survival, disease-free and progression-free survival, local failure, regional failure, and distant failure. A secondary endpoint included radiation-related toxicities. RESULTS: The median follow-up was 23.8 months (range 1.1-57.6). The 3-year local control, progression-free survival, and overall survival rates were 91, 55, and 71%, respectively. The median age at diagnosis was 67.9 years (range 51.4-87.1). There were a total of 54 T1N0 tumors (92%) and 5 T2N0 lesions (8%). Adenocarcinoma was the most common pathology, comprising 54% of the lesions. A total of 16 of the patients (29%) failed. Among these, 5 local (9%), 14 regional (25%), and 4 distant failures (7%) were observed. On follow-up, one patient had grade 2 and another had grade 5 pneumonitis. Three patients experienced grade 2 chest wall tenderness. Two patients had grade 1 rib fractures, one of which could not be discerned from radiation-induced toxicity versus a traumatic fall. CONCLUSION: The University of Mississippi Medical Center SBRT experience has shown that SBRT provides satisfactory local control and overall survival rates with minimal toxicity in early-stage NSCLC patients.

Integrative genomic analysis for the discovery of biomarkers in prostate cancer.

Genome-wide association studies (GWAS) have achieved great success in identifying single nucleotide polymorphisms (SNPs, herein called genetic variants) and genes associated with risk of developing prostate cancer. However, GWAS do not typically link the genetic variants to the disease state or inform the broader context in which the genetic variants operate. Here, we present a novel integrative genomics approach that combines GWAS information with gene expression data to infer the causal association between gene expression and the disease and to identify the network states and biological pathways enriched for genetic variants. We identified gene regulatory networks and biological pathways enriched for genetic variants, including the prostate cancer, IGF-1, JAK2, androgen, and prolactin signaling pathways. The integration of GWAS information with gene expression data provides insights about the broader context in which genetic variants associated with an increased risk of developing prostate cancer operate.

Transoral carbon dioxide laser supraglottic laryngectomy and irradiation in stage I, II, and III squamous cell carcinoma of the supraglottic larynx: report of Southwest Oncology Group Phase 2 Trial S9709.

OBJECTIVE: To evaluate feasibility, functional outcome, and disease control of endoscopic surgery and irradiation in patients with squamous cell carcinoma of the supraglottic larynx. DESIGN: Prospective, single-arm, phase 2 multi-institutional trial. SETTING: Southwest Oncology Group trial S9709. PATIENTS: Thirty-four patients diagnosed as having stage I, stage II, or selected stage III (T1-2N1M0) supraglottic laryngeal carcinoma enrolled from September 15, 1997, to December 1, 2001. INTERVENTIONS: Transoral supraglottic laryngectomy by carbon dioxide laser followed by planned postoperative radiotherapy. MAIN OUTCOME MEASURES: Three-year progression-free survival, proportion of patients requiring tracheostomy as a result of surgery, and time to adequate oral intake. RESULTS: All 34 patients underwent surgery without major protocol deviation. Thirty-two patients (94%) completed planned postoperative radiotherapy without major deviation. At the time of analysis, only 1 patient (3%) had documented local disease recurrence at the primary disease site and required salvage total laryngectomy, and 2 patients (6%) had documented regional recurrence and required salvage neck dissection. Estimated 3-year progression-free survival and overall survival were 79% and 88%, respectively. No subjects required tracheostomy as a direct consequence of endoscopic resection. Patients who required tracheostomy before endoscopic resection due to either obstructive tumor bulk or unfavorable anatomy that precluded safe intubation (4 patients [12%]) were all decannulated in the early postoperative period (

Report from the Radiation Oncology Committee of the Southwest Oncology Group (SWOG): Research Objectives Workshop 2003.

To achieve the ultimate goal of cancer treatment, which is 100% cancer control with negligible toxicity, the therapeutic window must be enlarged, allowing for higher doses of beneficial treatments with reduced toxicity. The advent of image- and metabolism-guided therapy offers the best opportunity to date for combining modern radiation targeting and imaging techniques. Indeed, for the first time, it is reasonable to locally target metastatic disease with the goal of sterilization. Combining these focal radiation techniques with novel targeted antiproliferative agents and full-dose classic cytotoxic chemotherapy will become more effective as we learn to use these compounds in a less systemically toxic manner and as radiation fields become more defined. In addition, increasing numbers of biologic modifiers of normal tissue response are becoming available, and they suggest great promise for decreasing the normal tissue toxicity resulting from both radiation and chemotherapy treatments. Thus, radiation metastectomy for gross metastases, used together with systemic control of micrometastatic disease, may yield improved survival rates. This hypothesis is ready for testing in cancers of the breast, prostate, colon, and in sarcomas. Enlarging the therapeutic window is a major goal that would allow for an increasingly favorable therapeutic gain.