Person:

Tanguturi, Shyam

Purpose. We investigated whether NS-RP increased risk of PSA failure and whether PSA should be included as a selection criterion for NS. Methods:. We evaluated 357 consecutive men with screen-detected PC who underwent open RP without adjuvant radiotherapy between 9/11/2001 and 12/30/2008. Criteria for NS included Gleason score ≤3 + 4, percentage of positive biopsies (PPB) ≤50%, percentage of core involvement ≤50%, nonapical location, no perineural invasion, and no palpable disease on pre- or intraoperative exam but did not include a PSA threshold. Cox multivariable regression assessed whether increasing PSA or unilateral- or bilateral-NS versus non-NS-RP was associated with PSA failure adjusting for prognostic factors. Results:. After a median follow-up of 3.96 years, 34 men sustained PSA failure (9.5%). Increasing PSA was significantly associated with increased risk of PSA failure in the interaction model (adjusted hazard ratio (AHR): 1.09 [95% CI: 1.03–1.16]; P = 0.005), whereas unilateral (AHR: 1.24 [95% CI: 0.36–4.34]; P = 0.73) or bilateral NS (AHR: 0.41 [95% CI: 0.06–2.59]; P = 0.34) versus non-NS RP was not. Conclusion:. NS-RP in a screened cohort did not increase risk of PSA failure using NS criteria not including PSA.

Background:. Whole lung irradiation (WLI) is a standard treatment component for children with metastatic Ewing Sarcoma (ES), but data on WLI for adults are sparse. Design:. An email survey was sent to expert sarcoma-dedicated oncologists worldwide: An adult with excellent performance status presents with primary ES in the leg and multiple pulmonary metastases. The patient achieves complete radiographic response after chemotherapy and resection of the primary. Would you give bilateral WLI to (1) this adult patient?, (2) this patient if 20 years old (yo)?, (3) this patient if 45 yo?, or (4) this patient if 60 yo? Results. 38 experts responded, including 24 adult, 1 adolescent young adult, and 13 pediatric oncologists. 63%, 63%, 62%, and 50% of respondents offered WLI to the adult, 20-year-old, 45-year-old, and 60-year-old, respectively. Pediatric oncologists more likely endorsed WLI across all ages including the adult (P = 0.01), 20-year-old (P = 0.005), 45-year-old (P = 0.01), and 60-year-old (P = 0.08). There were no significant differences between medical and radiation oncologists or between European/Australian and American providers. Conclusions:. Almost two-thirds of experts surveyed supported WLI for adults with metastatic ES up to age 45 and half supported WLI for a 60-year-old. Continued collaboration across adult and pediatric oncology is needed to define evidence-based strategies across the age spectrum.

The worldwide burden of sickle cell disease is enormous, with over 200,000 infants born with the disease each year in Africa alone. Induction of fetal hemoglobin is a validated strategy to improve symptoms and complications of this disease. The development of targeted therapies has been limited by the absence of discrete druggable targets. We developed a unique bead-based strategy for the identification of inducers of fetal hemoglobin transcripts in primary human erythroid cells. A small-molecule screen of bioactive compounds identified remarkable class-associated activity among histone deacetylase (HDAC) inhibitors. Using a chemical genetic strategy combining focused libraries of biased chemical probes and reverse genetics by RNA interference, we have identified HDAC1 and HDAC2 as molecular targets mediating fetal hemoglobin induction. Our findings suggest the potential of isoform-selective inhibitors of HDAC1 and HDAC2 for the treatment of sickle cell disease.