Validation of the Decipher genomic classifier in patients receiving salvage radiotherapy without hormone therapy after radical prostatectomy - an ancillary study of the SAKK 09/10 randomized clinical trial.

BACKGROUND: The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase III trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy. PATIENTS AND METHODS: A clinical-grade whole-transcriptome assay was carried out on radical prostatectomy samples obtained from patients enrolled in Swiss Group for Clinical Cancer Research (SAKK) 09/10, a phase III trial of 350 men with biochemical recurrence after radical prostatectomy randomized to 64 Gy versus 70 Gy without concurrent hormonal therapy or pelvic nodal RT. A prespecified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, postradical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks. RESULTS: The analytic cohort of 226 patients was representative of the overall trial, with a median follow-up of 6.3 years (interquartile range 6.1-7.2 years). The GC (high versus low-intermediate) was independently associated with biochemical progression [subdistribution hazard ratio (sHR) 2.26, 95% confidence interval (CI) 1.42-3.60; P < 0.001], clinical progression (HR 2.29, 95% CI 1.32-3.98; P = 0.003), and use of hormone therapy (sHR 2.99, 95% CI 1.55-5.76; P = 0.001). GC high patients had a 5-year freedom from biochemical progression of 45% versus 71% for GC low-intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower versus higher GC scores. CONCLUSIONS: This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. These data confirm the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting.

Value of fine-needle aspiration cytology of parotid gland masses.

OBJECTIVE: To evaluate the usefulness and accuracy of fine-needle aspiration cytology (FNAC) in the diagnosis of parotid gland masses. STUDY DESIGN: Retrospective chart review of patients undergoing FNAC. METHODS: Between January 1990 and December 1998, 410 parotid glands were resected at the Department of Otorhinolaryngology-Head and Neck Surgery at the University of Berne, Inselpital (Berne, Switzerland). Included in the study were 228 cases with preoperative FNAC. In a retrospective study the results of FNAC were analyzed and compared with the corresponding histopathological diagnosis. RESULTS: Histological evaluation revealed 65 malignant tumors and 163 benign lesions (150 neoplasms and 13 nonneoplastic lesions). The cytological findings were nondiagnostic in 13 (5.7%), true-negative in 146 (64%), true-positive in 39 (17%), false-negative in 22 (9.8%) and false-positive in 8 (4.5%) cases in detecting malignant tumors. Nineteen of 39 (49%) malignant tumors (true-positive) and 123 of 146 (84%) benign lesions (true-negative) were classified accurately. The accuracy, sensitivity, and specificity were 86%, 64%, and 95% respectively. CONCLUSIONS: Fine-needle aspiration cytology is a valuable adjunct to preoperative assessment of parotid masses. Preoperative recognition of malignant tumors may help prepare both the surgeon and patient for an appropriate surgical procedure.

Temporal analysis of DNA restriction digests by capillary electrophoresis.

We demonstrate a facile means for temporal analysis of DNA restriction enzyme digests by capillary electrophoresis-laser-induced fluorescence (CE-LIF) detection. phi X-174 DNA was digested with HaeIII restriction enzyme under conditions that allowed the monitoring of digestion as it proceeded toward completion. Separation by a polymer solution of methylcellulose in a polyacrylamide coated capillary allowed high resolution and a high degree of reproducibility between sequential runs. At pre-selected time intervals an injection of the digest, directly from the reaction mixture, was made. Sensitive detection was achieved by using ethidium bromide as an intercalation dye and allowing intercalation to occur on-column. It is demonstrated that the course of the digestion (i.e., the creation and diminishing of fragment peaks) can be followed using this methodology. Also demonstrated is the ability to use temporal analysis to determine ideal conditions for producing a single cut within a cloning and expression vector (pET3a-PAI-1) which contains 11 potential restriction endonuclease cleavage sites. This initial attempt to follow a restriction digest on-column not only provides meaningful information for the biochemical researcher, but also furthers the use of CE a diagnostic tool for the biochemical laboratory.