S.P. Giri

Integrative Genomic Analysis for the Discovery of Biomarkers in Prostate Cancer

Genome-wide association studies (GWAS) have achieved great success in identifying single nucleotide polymorphisms (SNPs, herein called genetic variants) and genes associated with risk of developing prostate cancer. However, GWAS do not typically link the genetic variants to the disease state or inform the broader context in which the genetic variants operate. Here, we present a novel integrative genomics approach that combines GWAS information with gene expression data to infer the causal association between gene expression and the disease and to identify the network states and biological pathways enriched for genetic variants. We identified gene regulatory networks and biological pathways enriched for genetic variants, including the prostate cancer, IGF-1, JAK2, androgen, and prolactin signaling pathways. The integration of GWAS information with gene expression data provides insights about the broader context in which genetic variants associated with an increased risk of developing prostate cancer operate.

Stereotactic body radiation therapy in lung

Lung cancer is the leading cause of cancer death worldwide, in both men and women. Contrary to the improved survival outcomes for many other types of cancers, the prognosis for people diagnosed with lung cancer remains poor, with 5-year relative survival ranging 6-18%. Majority of lung cancers diagnosed at locally advanced stage, due to the lack of observable symptoms for early stage lung cancer. Recently Lung Cancer screening in high-risk population with low dose CT scan showed 20% reduction in relative death from cancer. Screening allows diagnosing the cancer at early stage. For early (local only) stage, lobectomy is he treatment of choice that offers best 5-year overall survival of 60%. But majority of these patients are unable to tolerate the surgery due to poor pulmonary reserve or medical co morbidity. With the advent of new technology, improvements in imaging and treatment delivery enable us to extend the stereotactic radiation therapy to extra cranial sites. Stereotactic radiation therapy to lung reported 5-year local control rates in excess of 90% and overall survival of 40%. In this review article, we discussed the rationale, evidence supporting stereotactic body radiation therapy (SBRT) in lung tumors, radiobiology of hypofractionation, mediastinal staging, the treatment planning, and delivery process and also the role of SBRT in metastatic setting.

Abstract C85: Do African-American veterans need distinct “Prostate Cancer Screening Guidelines” to overcome outcome disparities?

Background: The United States Preventive Task Force recommended against the prostate-specific antigen (PSA)-based screening for prostate cancer in 2012, a recommendation that applies to all American men. African-American men, however, have the highest incidence of prostate cancer and are more likely to be diagnosed with an advanced stage and poor prognostic-form of prostate cancer. The incidence of prostate cancer is almost 60% higher, and the mortality rate is two- to three-times greater among African Americans than that of Caucasian men1. The Veteran9s Health Administration is an unbiased, race-color blind, equal and open access, single-payor, government run health care system2. Yet, due to complex interactions of ethnicity, biology, comorbidities, environmental interactions, as well as social causes, African-American veterans are present with more aggressive disease and carry a worse outcome. Therefore African-American veterans need specific interventions to improve prostate cancer outcomes; i.e., improve survivals and quality of life. We hypothesize that by developing specific and structured prostate cancer screening recommendations, we can improve the overall prostate cancer outcomes among African-American veterans. Methods: We performed a PubMed search using the keywords: African American, African American veterans, Prostate cancer, Outcomes, Molecular markers, Prostate-specific Antigen velocity, and PSA density to derive data relevant to our hypothesis. Results: 1. Men over the age of 65 are most susceptible to prostate cancer, and the average age of veterans is 582. So, they are at a nearly optimal age for preventative prostate cancer screening. 2. The USPSTF guidelines were based on two studies, and one of these studies reported that only 4% of its participants were African American. So, it is inappropriate to use the same guidelines for African American veterans. 3. Several aspects of prostate cancer are different between African Americans and Caucasians. These differences include prostate cancer incidence and outcome, genetic differences, comorbidity, PSA levels, social barriers, and course of the disease. 4. Prior to the new USPSTF guidelines, African American veterans were just as likely as white veterans to undergo PSA testing3. 5. Among the diseases linked to comorbidity with prostate cancer, cardiovascular disease is the most frequent. Hence, the leading cause of death in both the African-American population and the African-American veteran population is cardiovascular disease.2 Conclusion: 1. Because there is no cure for metastatic prostate cancer, early diagnosis and intervention for African-American veterans will lead to saving lives; specific guidelines for prostate cancer will be very beneficial. 2. This will also decrease the costs of treating recurrent and metastatic disease and conserve the resources of the VA Health System. 3. Because the Veterans Health System is equal access, it is an optimal environment to test different prostate cancer screening guidelines for African Americans. 4. Specific draft guidelines will be presented. References: 1. Shenoy D, Packianathan S, Chen AM, Vijayakumar S. Do African-American men need separate prostate cancer screening guidelines? BMC Urology. 2016;16:19. doi:10.1186/s12894-016-0137-7. 2. Veterans Health Administration. Veterans Health Administration. http://www.va.gov/health/. Published June 21, 2016. Accessed June 23, 2016. 3. Hudson MA, Luo S, Chrusciel T, et al. Do Racial Disparities Exist in the Use of Prostate Cancer Screening and Detection Tools in Veterans? Urologic oncology. 2014;32(1):34.e9-34.18. doi:10.1016/j.urolonc.2013.01.003. Citation Format: Arthi Gadum Reddy, Divya Shenoy, Satya Packianathan, Shankar Giri, Srinivasan Vijayakumar. Do African-American veterans need distinct “Prostate Cancer Screening Guidelines” to overcome outcome disparities? [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C85.

Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer: A Retrospective, Single-Center Study of 55 Patients.

Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) is an effective treatment for patients with early-stage non-small cell lung cancer (NSCLC) who are not surgical candidates or who refuse surgical management. In this study, we report on our clinical outcomes and toxicity in the treatment of early-stage NSCLC with SBRT. Methods and Materials: Fifty-five patients with 59 T1-2N0M0 NSCLC lesions were treated at our institution between December 2009 and August 2014. The majority of the patients [38 (69%)] were treated with 50 Gy in 5 fractions, 7 patients (13%) with 48 Gy in 4 fractions, 8 patients (14%) with 60 Gy in 3 fractions, 1 patient (2%) with 62.5 Gy in 10 fractions, and 1 patient (2%) with 54 Gy in 3 fractions. Tumor response was evaluated using RECIST 1.1, and toxicity was graded using the CTCAE (Common Terminology Criteria for Adverse Events) version 3.0. The primary endpoints of this retrospective review included rates of overall survival, disease-free and progression-free survival, local failure, regional failure, and distant failure. A secondary endpoint included radiation-related toxicities. Results: The median follow-up was 23.8 months (range 1.1-57.6). The 3-year local control, progression-free survival, and overall survival rates were 91, 55, and 71%, respectively. The median age at diagnosis was 67.9 years (range 51.4-87.1). There were a total of 54 T1N0 tumors (92%) and 5 T2N0 lesions (8%). Adenocarcinoma was the most common pathology, comprising 54% of the lesions. A total of 16 of the patients (29%) failed. Among these, 5 local (9%), 14 regional (25%), and 4 distant failures (7%) were observed. On follow-up, one patient had grade 2 and another had grade 5 pneumonitis. Three patients experienced grade 2 chest wall tenderness. Two patients had grade 1 rib fractures, one of which could not be discerned from radiation-induced toxicity versus a traumatic fall. Conclusion: The University of Mississippi Medical Center SBRT experience has shown that SBRT provides satisfactory local control and overall survival rates with minimal toxicity in early-stage NSCLC patients.

SU-E-T-504: Usefulness of CT-MR Fusion in Radiotherapy Planning for Prostate Cancer Patient with Bilateral Hip Replacements

PURPOSE Target localization of prostate for Intensity Modulated Radiation Therapy (IMRT) in patients with bilateral hip replacements is difficult due to artifacts in Computed Tomography (CT) images generated from the prostheses high Z materials. In this study, Magnetic Resonance (MR) images fused with CT images are tested as a solution. METHODS CT images of 2.5 mm slice thickness were acquired on a GE Lightspeed scanner with a flat-topped couch for a prostate cancer patient with bilateral hip replacements. T2 weighted images of 5 mm separation were acquired on a MR Scanner. After the MR-CT registration on a radiotherapy treatment planning system (Eclipse, Varian), the target volumes were defined by the radiation oncologists on MR images and then transferred to CT images for planning and dose calculation. The CT Hounsfield Units (HU) was reassigned to zero (as water) for artifacts. The Varian flat panel treatment couch was modeled for dose calculation accuracy with heterogeneity correction. A Volume Matrix Arc Therapy (VMAT) and a seven-field IMRT plans were generated, each avoiding any beam transversing the prostheses; the two plans were compared. The superior VMAT plan was used for treating the patient. In-vivo dosimetry was performed using MOSFET (Best Canada) placed in a surgical tube inserted into the patient rectum during therapy. The measured dose was compared with planned dose for MOSFET location. RESULTS The registration of MR-CT images and the agreement of target volumes were confirmed by three physicians. VMAT plan was deemed superior to IMRT based on dose to critical nearby structures and overall conformality of target dosing. In-vivo measured dose compared with calculated dose was -4.5% which was likely due to attenuation of the surgical tube surrounding MOSFET. CONCLUSION When artifacts are present on planning CT due to bilateral hip prostheses, MR-CT image fusion is a feasible solution for target delineation.