Vasu Tumati

Background: This study sought to determine the oncologic impact of delays to surgery, radiotherapy, and completion of therapy in patients with head and neck squamous cell carcinoma.Methods: The impact of biopsy to surgery (BTS) time, surgery to start of radiation time (STSR), and radiation treatment time (RTT) on locoregional recurrence (LRR), distant metastases (DMs), and cancer‐specific mortality (CSM) was examined. The cumulative incidences (CI) of LRR, DMs, and CSM were examined using Fine–Gray testing.Results: A total of 277 patients treated with surgery and adjuvant radiotherapy were analyzed. On multivariable testing, BTS >50 days was associated with DM (P = .03), whereas RTT and STSR were not. RTT >43 days was associated with LRR (P = .02) in patients with non‐p16‐positive‐oropharynx cancer.Conclusions: An increase in DM appears to be the mechanism by which prolonged time to treatment initiation leads to worse overall survival. Prolonged RTT has the greatest impact on patients with non‐p16 positive oropharynx cancers.

Objectives: To characterise the frequency and detailed anatomical sites of failure for patients receiving post‐radical prostatectomy (RP) salvage radiation therapy (SRT). Patients and Methods: A multi‐institutional retrospective study was performed on 574 men who underwent SRT between 1986 and 2013. Anatomical recurrence patterns were classified as lymphotrophic (lymph nodes only), osteotrophic (bone only), or multifocal if both were present. Isolated first failure sites were defined as sites of initial clinically detected recurrence that remained isolated for at least 3 months. Results: The median follow‐up after SRT was 6.8 years. The 8‐year rates of local, regional, and distant failure for patients undergoing SRT were 2%, 6%, and 21%, respectively. Of the 22% men (128 of 574) who developed a clinically detectable recurrence, 17%, 50%, and 31% were lymphotrophic, osteotrophic, and multifocal, respectively. The trophic nature of metastases was prognostic for distant metastases‐free survival (DMFS) and prostate cancer‐specific survival (PCSS); the 10‐year rates of DMFS were 18%, 5%, and 7% ( P < 0.01), and PCSS were 78%, 68%, and 56% ( P < 0.01), for lymphotrophic, osteotrophic, and multifocal failure patterns, respectively. Conclusions: We demonstrate that trophism for metastatic site has significant prognostic impact on PCSS in men treated with SRT. Radiographic local failure is an uncommon event after SRT when compared to historical data of patients treated with surgery monotherapy. However, distant failure remains a challenge in this patient population and warrants further therapeutic investigation.

E16553 Background: Our pilot study, which analyzed DAB2IP expression in 46 patients' biopsies and had short follow up, showed that DAB2IP reduction correlates with worse outcome in patients with high-risk prostate cancer treated with radiation therapy and androgen deprivation. With longer follow up and increased sample size, we hypothesized that pretreatment tumor status of DAB2IP would also predict worse prostate cancer-specific survival (PCSS). Methods: Immunohistochemistry of pretreatment biopsies was scored by an expert genitourinary pathologist. PCSS was defined as death due to prostate cancer, radiation toxicity, or unknown cause with distant metastasis or castration resistance. Other endpoints analyzed include freedom from biochemical failure (FFBF), castration resistance-free survival (CRFS), and distant metastasis-free survival (DMFS). Results: 79 patients with NCCN-defined high-risk prostate cancer treated with radiotherapy from 2005-2012 at our institution were evaluated. 28% (22/79) of pretreatment biopsies revealed DAB2IP-reduction while 72% (57/79) retained DAB2IP expression. The median follow up times were 4.8 years and 5.3 years for patients in the DAB2IP-reduced group and DAB2IP-retained group, respectively. Patients with reduced DAB2IP were statistically more likely to have higher T stage (p = 0.0149), pretreatment PSA (p = 0.0379), and Gleason scores (p = 0.0048). Patients with reduced DAB2IP also demonstrated worse outcome compared to patients retaining DAB2IP, including FFBF (4-year: 34% vs. 92%; p < 0.0001), CRFS (4-year: 58% vs. 96%; p = 0.0039), DMFS (4-year: 58% vs. 100%; p = 0.0006), and PCSS (5-year: 83% vs. 100%; p = 0.0102). Univariate analysis showed T stage, N stage, and Gleason score were statistically significant variables. Pretreatment tumor DAB2IP status remained significant in the multivariable analysis. Conclusions: This study suggests that about one-fourth of men with high-risk prostate cancer have decreased DAB2IP tumor expression. This subpopulation with reduced DAB2IP has a suboptimal response and worse PCSS following radiation therapy and androgen deprivation. Further study into improving treatment response and survival in this subpopulation is warranted.

133 Background: 20% of men with prostate cancer (PCa) are diagnosed with high-risk disease. The optimal therapy for these patients, prostatectomy followed by adjuvant radiation therapy (ART) or definitive radiation with androgen deprivation (DRT), is still unclear. Previous randomized trials failed to accrue; therefore we sought to answer this using an IRB-approved retrospective cohort study. Methods: High-risk PCa was defined using NCCN criteria. Adjuvant radiation was defined as radiotherapy started within 6 months of prostatectomy. Biochemical progression-free survival (BPFS), castrate resistance-free survival (CRFS), distant metastasis-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were calculated using Kaplan-Meier estimates. Biochemical failure was defined using the AUA definition in the ART group and by the Phoenix definition in the DRT group. Castrate resistance was defined as ≥2 episodes of rising PSA with testosterone

NSCLC cells demonstrate differential mode of cell death in response to the combined treatment of radiation and a DNA-PKcs inhibitor NSCLC cells demonstrate differential mode of cell death in response to the combined treatment of radiation and a DNA-PKcs inhibitor

One of the many issues of using radiosensitizers in a clinical setting is timing daily radiation treatments to coincide with peak drug concentration in target tissue. To overcome this deficit, we have synthesized a novel nanoparticle (NP) system consisting of poly (lactic‐co‐glycolic acid) (PLGA) NPs conjugated with prostate cancer cell penetrating peptide‐R11 and encapsulated with a potent radio‐sensitizer 8‐dibenzothiophen‐4‐yl‐2‐morpholin‐4‐yl‐chromen‐4‐one (NU7441) to allow prostate cancer‐specific targeting and sustained delivery over 3 weeks. Preliminary characterization studies showed that the R11‐conjugated NPs (R11‐NU7441 NPs) had an average size of about 274 ± 80 nm and were stable for up to 5 days in deionized water and serum. The NPs were cytocompatible with immortalized prostate cells (PZ‐HPV‐7). Further, the particles showed a bi‐phasic release of encapsulated NU7441 and were taken up by PC3 prostate cancer cells in a dose‐ and magnetic field‐dependent manner while not being taken up in nonprostate cancer cell lines. In addition, R11‐NU7441 NPs were effective radiation sensitizers of prostate cancer cell lines in vitro. These results thus demonstrate the potential of R11‐conjugated PLGA NPs as novel platforms for targeted radiosensitization of prostate cancer cells. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1632–1639, 2015.