Ruchika Gutt

Statin Use and Risk of Prostate Cancer Recurrence in Men Treated With Radiation Therapy

PURPOSE There has been growing interest in the potential anticancer activity of statins based on preclinical evidence of their antiproliferative, proapoptotic, and radiosensitizing properties. The primary objective of this study was to determine whether statin use is associated with improved clinical outcomes in patients treated with radiotherapy (RT) for prostate cancer. PATIENTS AND METHODS In total, 691 men with prostate adenocarcinoma treated with curative-intent RT between 1988 and 2006 were retrospectively analyzed. Of those, 189 patients (27%) were using statins, either during initial consultation or during follow-up. Lipid panels were collected (n = 298) a median of 5 months before RT start. Median follow-up was 50 months after RT. RESULTS Statin use was associated with improved freedom from biochemical failure (FFBF; P < .001), freedom from salvage androgen deprivation therapy (FFADT; P = .0011), and relapse-free survival (RFS; P < .001). Improved FFBF for statin users was seen in low-, intermediate-, and high-risk groups (P = .0401, P = .0331, and P = .0034, respectively). The improvement in FFBF with statin use was independent of ADT use or radiation dose. On multivariable analysis, statin use was associated with improved FFBF (P < .001) along with pretreatment prostate-specific antigen < or = 8.4 (P < .001), stage less than T2b (P = .0111), and Gleason score < 7 (P = .0098). On univariate analysis, pretreatment total cholesterol < 187 (89% v 80%; P = .0494) and low-density lipoprotein (LDL) < 110 (96% v 85%; P = .0462) were associated with improved 4-year FFBF. CONCLUSION Statin use was associated with a significant improvement in FFBF, FFADT, and RFS in this cohort of men treated with RT for prostate cancer. The favorable effect of statins may be mediated by direct effect or via the LDL-lowering effect of these medications.

The role of radiotherapy in locally advanced pancreatic carcinoma

The prognosis for locally advanced pancreatic carcinoma remains dismal despite advances in chemotherapy and radiotherapy over the past few decades. The use of radiotherapy for pancreatic carcinoma is often disputed because of the hypothesis that patients with pancreatic cancer die from distant metastases. It is well accepted that the greatest chance for cure of pancreatic cancer involves surgical resection of the primary tumor. However, there is much controversy about the role of radiotherapy in local disease control. The aim of this Review is to discuss data from the available studies, both prospective and retrospective, that evaluate treatment options for locally advanced pancreatic cancer. We focus on the benefits associated with local therapies, including radiotherapy and surgical resection, as they relate to improved local disease control, prolonged overall survival and improved symptom control.

Adjuvant radiotherapy for resected pancreatic cancer: a lack of benefit or a lack of adequate trials?

Surgical resection is the most effective means of controlling nonmetastatic pancreatic cancer, but recurrence rates are high even after complete resection. For several types of tumor of the gastrointestinal tract, combined modality therapy that includes radiation therapy has been shown to reduce the recurrence rate and improve disease-free survival. The use of adjuvant radiotherapy for pancreatic cancer, however, is controversial. Results of the few randomized trials of adjuvant radiotherapy for pancreatic cancer are conflicting. In addition, as pancreatic cancer is associated with high rates of distant recurrence, the additional benefit provided by local therapy has been perceived as questionable. This article reviews the studies—prospective and retrospective—of adjuvant radiotherapy for pancreatic cancer and the issues surrounding the use of this strategy.

Advanced radiation oncology technology within the Veterans Health Administration (VHA).

52 Background: The rapid evolution of technology in the treatment of cancer has paralleled other technological advancements in modern society. Intensity Modulated Radiotherapy (IMRT), Image Guided Radiotherapy (IGRT), Brachytherapy (BT), Cone Beam Computed Tomography (CBCT), Stereotactic Radiosurgery (SRS), and Stereotactic Body Radiotherapy (SBRT) facilitate treatment with higher, more conformal radiation doses, potentially improving cancer control while reducing normal tissue toxicity. Recent Surveillance, Epidemiology and End Results (SEER) program data and physician surveys indicate prostate BT is declining and the integration of SRS and SBRT is slower compared to IMRT. As utilization of technology increases, an understanding of its availability within the VHA is necessary to ensure quality and patient safety. METHODS An electronic survey was sent to 82 Radiation Oncologists (ROs)at 38 active VHA Radiation Oncology Centers with subsequent follow-up phone calls. The survey occurred from May-June 2014. ROs were queried on the availability of advanced RT technologies including IMRT, IGRT, BT, CBCT, SRS and SBRT at their facility. Practitioner specific details: years in practice, academic appointment and VHA employment status were collected. RESULTS Responses were obtained from 62 ROs representing 75% of VHA ROs and 34 or 89% of facilities. Full time VHA employees made up 60% of respondents with 35% in practice for <5 years and 34% practicing for >20 years; 71% held an academic appointment. The Table shows on site availability of advanced RT technologies within the 34 VHA sites that responded. CONCLUSIONS For veterans receiving cancer treatment, VHA ROs are able to routinely use IMRT and IGRT with CBCT capabilities. However, stereotactic (SRS and SBRT) and BT services are less available, and may require referrals externally or to other VHA facilities. Limited availability of SRS and SBRT parallels the community experience. Likewise the decreasing utilization of BT is common to the VHA and private sector. SBRT, SRS and BT require significant expertise and technology. [Table: see text].

The availability of and satisfaction with palliative care services among VHA-based radiation oncologists.

55 Background: Palliative care services enhance quality of life in patients with advanced malignancies and are an integral component of multidisciplinary cancer care. They provide symptom control and psychosocial support for patients and family members. A survey in non-VHA cancer centers showed that despite availability of palliative care programs, there was wide variability in the use of these services (Hui et al, JAMA 2010). Palliative care services are a component of the VHA medical benefits package. We sought to determine the ease of access to palliative care services and provider satisfaction among VHA Radiation Oncologists. METHODS VHA-based Radiation Oncologists were identified using the National VHA Radiation Oncology list serve group. All practicing Radiation Oncologists were surveyed to determine the extent of Palliative Care Services available to them and to measure their level of satisfaction with these services. Eighty two surveys were electronically mailed to practitioners at the 38 active VHA Radiation Oncology sites, followed by a reminder phone call.This survey was conducted over a four week period in May of 2014. RESULTS Sixty four of the 82 surveys distributed over the 4 week period, or 78% were completed. They represent 89% (34/38) of VHA Radiation Oncology Services. All respondents had Palliative Care Services available to them and 98% were happy with the services rendered by the Palliative Care teams. CONCLUSIONS All VHA-based Radiation Oncologists who responded to this survey have access to local VHA based Palliative Care Services. This represented 82% of VHA Radiation Oncology practitioners and 98% were satisfied with the services rendered. Further studies should explore the scope and extent of palliative care involvement including when these services are integrated into the management of patients with advanced malignancies, availability of outpatient palliative care services and variations in care delivery. Radiation therapy is utilized in over 50% of patients with malignancy, often in advanced disease for symptom management and standard guidelines integrating radiotherapy and palliative care should be developed.

Abstract 573: Ionizing radiation activates IFN signaling in tumor cells

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Ionizing radiation (IR) uses multiple pathways to mediate killing in tumor cells. We found that fractionated irradiation leads to the constitutive overexpression of Interferon Stimulated Genes (ISGs) which are controlled by Signal Transducer and Activator of Transcription 1 (Stat1). Stat1 mediated IFN signal transduction and at the same time was involved in the production of Type I and Type II IFNs. IR-induced ISGs represent the following groups: 1) mitochondrial-related genes with pro- and anti-apoptotic functions, 2) cell cycle control and regulators of transcription, 3) protein modification and degradation, 4) cytoplasmic sensors of nucleic acids, and 5) anti-viral defense. Fractionated or single-dose IR induced the IFN pathway mediated by activation of Stat1 in breast, colon, prostate and head and neck tumor xenografts. Depletion of tumor-derived IFNs led to the suppression of IR response indicating that IFN production/signaling is a component of anti-tumor IR action. Cell-autonomous experiments indicated that tumor cells up-regulate Stat1 and ISGs and produce IFNα in response to single dose IR (3Gy). Up-regulated Stat1 in irradiated tumor cells was not phosphorylated at Tyr701 position compared to Stat1 activation following interferon stimulation. In a syngeneic tumor model of B16F1, IR-induced activation of IFN signaling in tumors (assessed both by up-regulation of the Stat1-dependent pathway and induction of Type I and Type II IFNs) was dependent on TNFα signaling in the host and was impaired in TNFR1,2-/- mice. We therefore conclude that IR induces IFN signaling in tumor cells as a component of the cytotoxic response. This interferon induction depends on TNFα signaling in host cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 573. doi:10.1158/1538-7445.AM2011-573