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Biomedical subjects

Javier F Torres-Roca

Publications and source records attributed to Javier F Torres-Roca.

4 recordsLinked to original sources

The role of external-beam radiation therapy in the treatment of clinically localized prostate cancer.

BACKGROUND: The treatment of clinically localized prostate cancer is controversial. Options include radical prostatectomy, external-beam radiation therapy (EBRT), brachytherapy, cryotherapy, and watchful waiting. METHODS: The author reviews EBRT as treatment for clinically localized prostate cancer, with particular emphasis on the technological advances that have allowed dose escalation and fewer therapy-related side effects. RESULTS: Technological advances in the last two decades have significantly improved the delivery of EBRT to the prostate. This has resulted in an overall increase in the total dose that can be safely delivered to the prostate, which has led to modest improvements in biochemical outcome. An alternative approach of combining androgen suppression therapy and EBRT has also been successful in improving clinical outcomes. However, establishing the optimal therapy for prostate cancer remains controversial. CONCLUSIONS: Recent progress has led to improvements in clinical outcomes in patients treated with EBRT for prostate cancer. It is hoped that the next decades will bring continued advances in the development of biologicals that will further improve current clinical outcomes.

Brachytherapy↗

Prediction of radiation sensitivity using a gene expression classifier.

The development of a successful radiation sensitivity predictive assay has been a major goal of radiation biology for several decades. We have developed a radiation classifier that predicts the inherent radiosensitivity of tumor cell lines as measured by survival fraction at 2 Gy (SF2), based on gene expression profiles obtained from the literature. Our classifier correctly predicts the SF2 value in 22 of 35 cell lines from the National Cancer Institute panel of 60, a result significantly different from chance (P = 0.0002). In our approach, we treat radiation sensitivity as a continuous variable, significance analysis of microarrays is used for gene selection, and a multivariate linear regression model is used for radiosensitivity prediction. The gene selection step identified three novel genes (RbAp48, RGS19, and R5PIA) of which expression values are correlated with radiation sensitivity. Gene expression was confirmed by quantitative real-time PCR. To biologically validate our classifier, we transfected RbAp48 into three cancer cell lines (HS-578T, MALME-3M, and MDA-MB-231). RbAp48 overexpression induced radiosensitization (1.5- to 2-fold) when compared with mock-transfected cell lines. Furthermore, we show that HS-578T-RbAp48 overexpressors have a higher proportion of cells in G2-M (27% versus 5%), the radiosensitive phase of the cell cycle. Finally, RbAp48 overexpression is correlated with dephosphorylation of Akt, suggesting that RbAp48 may be exerting its effect by antagonizing the Ras pathway. The implications of our findings are significant. We establish that radiation sensitivity can be predicted based on gene expression profiles and we introduce a genomic approach to the identification of novel molecular markers of radiation sensitivity.

Carrier Proteins↗

Treatment of intermediate-risk prostate cancer with brachytherapy without supplemental pelvic radiotherapy: a review of the H. Lee Moffitt Cancer Center experience.

PURPOSE: To determine the biochemical outcomes of patients with intermediate-risk prostate cancer treated at the H. Lee Moffitt Cancer Center with an I-125 permanent seed implant without supplemental pelvic radiotherapy. METHODS AND MATERIALS: Under an institutional review board approved protocol, the charts of 88 patients with intermediate-risk prostate cancer and a minimum follow-up of 36 months treated with brachytherapy without supplemental pelvic radiotherapy were reviewed. Median follow-up for the whole cohort was 57 months (range 37-121). Biochemical failure was defined using the American Society for Therapeutic Radiology and Oncology definition. RESULTS: The 5-year biochemical failure-free survival for the cohort was 83%. Patients with perineural invasion had a worse biochemical outcome, which was statistically significant (perineural invasion vs. no perineural invasion, 5-year biochemical failure-free survival 64% vs. 89%, P = 0.004). None of the following factors were found significant in this subset of patients: Gleason scores 6 versus 7, primary Gleason grades 3 versus 4, percentage of core positive <20% versus >20%, number of cores positive <2 versus 2 versus >2, hormonal therapy versus no hormonal therapy, T1 versus T2, prostate-specific antigen <10 versus >10, or > or =2 intermediate risk factors versus 1 intermediate risk factor. CONCLUSIONS: Our data suggest that patients with intermediate-risk prostate cancer may be treated effectively with brachytherapy without supplemental pelvic radiotherapy. However, because of the limited nature of our study, we cannot exclude that patients with intermediate-risk prostate cancer may benefit from supplemental external beam radiotherapy.

Brachytherapy↗

Bladder preservation protocols in the treatment of muscle-invasive bladder cancer.

BACKGROUND: Over the last 3 decades, we have seen a paradigm shift in our approach to the treatment of malignancy. During that time, organ conservation protocols have become standard in the treatment of breast cancer, laryngeal cancer, esophageal cancer, anal cancer and soft tissue sarcomas. METHODS: Data from reports of bladder preservation protocols were reviewed to evaluate organ preservation approaches in muscle-invasive bladder cancer. RESULTS: These trials have shown equivalent disease control rates when compared to radical surgery, with the advantage of organ function preservation. In spite of this, organ preservation efforts in muscle-invasive bladder cancer have lagged behind this overall trend in clinical oncology. However, efforts by several investigators over the last 2 decades have shown that for a number of selected patients with muscle-invasive bladder cancer, bladder preservation is feasible without an apparent compromise of overall survival. CONCLUSIONS: Bladder preservation therapy with a trimodality approach for a carefully selected patient population is safe and effective. Formal randomized trials comparing radical cystectomy and trimodality bladder-sparing therapy are justified.

Antineoplastic Agents↗