ABSTRACT
BACKGROUND: To evaluate whether single-nucleotide polymorphisms (SNPs) reflecting common variation in the tumor suppressor BRCA1 affect prostate cancer outcomes. Because radiation therapy (RT) induces DNA damage, we hypothesized that common variation in BRCA1 has a role in progression to lethal prostate cancer, particularly in patients receiving RT. METHODS: We followed 802 men diagnosed with localized prostate cancer (cT1-T3/N0/M0) who were treated with RT in the US Health Professionals Follow-up Study (HPFS) and Physicians' Health Study (PHS), for progression to lethal prostate cancer. Six SNPs (rs3737559, rs1799950, rs799923, rs915945, rs4474733 and rs8176305) were genotyped in HPFS to capture common variation across BRCA1. rs4474733 and rs8176305 were also evaluated in the PHS cohort. Cox proportional hazards models were used to estimate per-allele hazard ratios (HR) and 95% confidence intervals (CI) stratified by primary treatment. RESULTS: In the RT group (n=802), 71 men progressed to lethal disease during a mean follow-up of 12 years. We found that two SNPs, rs4473733 (HR: 0.65; 95% CI 0.42-0.99) and rs8176305 (HR: 2.03; 95% CI 1.33-3.10), were associated with lethal prostate cancer in men receiving RT. CONCLUSIONS: Common variation in BRCA1 may influence clinical outcomes in patients receiving RT for localized prostate cancer by modifying the response to RT. Our findings merit further follow-up studies to validate these SNPs and better understand their functional and biological significance.
Subject(s)
BRCA1 Protein/genetics , Genetic Variation , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Adult , Aged , Alleles , Combined Modality Therapy , DNA Damage , Disease Progression , Follow-Up Studies , Genotype , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Staging , Polymorphism, Single Nucleotide , Proportional Hazards Models , Prostatic Neoplasms/mortality , Prostatic Neoplasms/radiotherapyABSTRACT
BACKGROUND: In this meta-analysis, we evaluated associations between statins and recurrence-free survival (RFS) following treatment of localized prostate cancer, with attention to potential benefits among patients treated primarily with radiotherapy (RT) versus radical prostatectomy. PATIENTS AND METHODS: We identified original studies examining the effect of statins on men who received definitive treatment of localized prostate cancer using a systematic search of the PubMed and EMBASE databases through August 2012. Our search yielded 17 eligible studies from 794 references; 13 studies with hazard ratios (HRs) for RFS were included in the formal meta-analysis. RESULTS: Overall, statins did not affect RFS (HR 0.90, 95% CI 0.74-1.08). However, in RT patients (six studies), statins were associated with a statistically significant improvement in RFS (HR 0.68; 95% CI 0.49-0.93); this benefit was not observed in radical prostatectomy patients (seven studies). Sensitivity analyses suggested that primary treatment modality may impact the effect of statins on prostate cancer recurrence. CONCLUSIONS: Our meta-analysis suggests a potentially beneficial effect of statins on prostate cancer patients treated with RT but not among radical prostatectomy patients. Although limited by the lack of randomized data, these results suggest that primary treatment modality should be considered in future studies examining associations between statins and oncologic outcomes.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Prostatectomy/trends , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Humans , Male , Neoplasm Recurrence, Local/diagnosis , Prostatic Neoplasms/diagnosisABSTRACT
BACKGROUND: Hodgkin lymphoma (HL) survivors have an increased risk of secondary malignancies. We analyzed outcomes in patients with lung cancers following HL treatment. PATIENTS AND METHODS: Cases of thoracic malignancies were retrospectively identified from a multi-institutional database of 1976 patients treated for HL from 1969 to 2007. Data regarding risk factors, disease characteristics and outcomes were obtained from medical records. RESULTS: Lung malignancies were identified in 55 patients a median of 19.5 years after initial HL therapy. Thirty-one patients (56%) had a >10 pack-year history of tobacco use, 48 (87%) received thoracic irradiation and 26 (47%) received alkylating chemotherapy. Of the 42 patients with known stage at lung cancer diagnosis, 23 (55%) were stage IV and 5 (12%) were stage III. The method of lung cancer detection was known for 35 patients; of these, 12 (34%) were detected incidentally. Median survival time after diagnosis was 10 months for all 55 patients. Median survival time for patients with incidentally detected tumors has not been reached with a median follow-up of 39 months. CONCLUSIONS: Lung malignancies diagnosed in patients successfully treated for HL generally have a dismal prognosis. However, a subset of patients diagnosed incidentally may have potentially curable disease.
Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnosis , Hodgkin Disease/therapy , Lung Neoplasms/diagnosis , Neoplasms, Second Primary/diagnosis , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/mortality , Female , Humans , Incidental Findings , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Male , Middle Aged , Neoplasms, Second Primary/mortality , Retrospective Studies , Young AdultABSTRACT
The Trail Making Test (TMT) is one of the most frequently used measures in clinical neuropsychology. Data obtained from the TMT practice times were analyzed to determine their utility in predicting success and failure on the full version of the test and to allow establishment of criteria by which to judge administration or discontinuation of the full test. Results indicated that TMT practice times were useful in predicting successful completion of Part A and B of the TMT. Tables are provided which describe the classification accuracy of various TMT practice times. These tables allow clinicians to select a practice-time cutoff and then use the cutoff as a heuristic to assist in the decision to administer the remainder of that particular part of the TMT or discontinue the test. A 20-s cutoff resulted in optimal prediction of successful completion (< 180 s) of TMT Part A. A cutoff of 30 s optimally predicted successful completion (< 300 s) of TMT Part B.
