Medicine and Health Sciences Commons^™

Invariant Characteristics Of Carcinogenesis., Simon Sherman, Nirosha Rathnayake, Tengiz Mdzinarishvili

Journal Articles: Eppley Institute

Carcinogenic modeling is aimed at mathematical descriptions of cancer development in aging. In this work, we assumed that a small fraction of individuals in the population is susceptible to cancer, while the rest of the population is resistant to cancer. For individuals susceptible to cancer we adopted methods of conditional survival analyses. We performed computational experiments using data on pancreatic, stomach, gallbladder, colon and rectum, liver, and esophagus cancers from the gastrointestinal system collected for men and women in the SEER registries during 1975-2009. In these experiments, we estimated the time period effects, the birth cohort effects, the age effects …

A Phase 3 Trial Of 2 Years Of Androgen Suppression And Radiation Therapy With Or Without Adjuvant Chemotherapy For High-Risk Prostate Cancer: Final Results Of Radiation Therapy Oncology Group Phase 3 Randomized Trial Nrg Oncology Rtog 9902., Seth A. Rosenthal, Daniel Hunt, A. Oliver Sartor, Kenneth J. Pienta, Leonard G. Gomella, David Grignon, Raghu Rajan, Kevin J. Kerlin, Christopher U. Jones, Michael Dobelbower, William U Shipley, Kenneth Zeitzer, Daniel A. Hamstra, Viroon Donavanik, Marvin Rotman, Alan C. Hartford, Jeffrey Michalski, Michael Seider, Harold Kim, Deborah A. Kuban, Jennifer Moughan, Howard Sandler

Department of Urology Faculty Papers

PURPOSE: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS).

METHODS AND MATERIALS: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥ 7 or clinical stage ≥ T2 and GS ≥ 8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was …

Is Extended Volume External Beam Radiation Therapy Covering The Anastomotic Site Beneficial In Post-Esophagectomy High Risk Patients?, Edward Yu, Rashid Dar, George Rodrigues, Larry Stitt, Gregory Videtic, Pauline Truong, Anna Tomiak, Robert Ash, Ed Brecevic, Richard Inculet, Richard Malthaner, Mark Vincent, Ian Craig, Walter Kocha, Michael Lefcoe

Richard A. Malthaner

Background and purpose: To assess the impact of extended volume radiation therapy (RT) with anastomotic coverage on local control in high risk post-operative esophageal cancer patients.

Patients and methods: This is a retrospective study of high risk (T(3), T(4), nodes positive, with or without margin involvement) post-operative esophageal cancer patients treated at London Regional Cancer Centre from 1989 to 1999. After esophagectomy, all patients received adjuvant combined modality therapy consisting of four cycles of fluorouracil-based chemotherapy, and loco-regional RT with or without coverage of the anastomotic site. RT dose ranged from 45 to 60 Gy at 1.8-2.0 Gy/fraction with treatment …

Management And Prognosis In Synchronous Solitary Resected Brain Metastasis From Non–Small-Cell Lung Cancer, Alexander Louie, George Rodrigues, Brian Yaremko, Edward Yu, A. Dar, Brian Dingle, Mark Vincent, Michael Sanatani, Richard Malthaner, Richard Inculet

Richard A. Malthaner

Background: Reports in the medical literature have described cases of extended survival of patients with non-small-cell lung cancer (NSCLC) with solitary metastatic disease who have received aggressive treatment both to the brain metastasis and to the local/regional disease. The objective of this research is to analyze prognostic factors that predict for outcome in this unique patient population.

Patients and methods: A single-institution, retrospective chart review was performed on 35 patients with NSCLC and a synchronous solitary brain metastasis (SSBM) treated with craniotomy and whole-brain radiation therapy. Eight patients (22.9%) had chest surgery, 24 (68.6%) had chemotherapy, and 14 (40%) had …

Is Extended Volume External Beam Radiation Therapy Covering The Anastomotic Site Beneficial In Post-Esophagectomy High Risk Patients?, Edward Yu, Rashid Dar, George Rodrigues, Larry Stitt, Gregory Videtic, Pauline Truong, Anna Tomiak, Robert Ash, Ed Brecevic, Richard Inculet, Richard Malthaner, Mark Vincent, Ian Craig, Walter Kocha, Michael Lefcoe

Richard A. Malthaner

Background and purpose: To assess the impact of extended volume radiation therapy (RT) with anastomotic coverage on local control in high risk post-operative esophageal cancer patients.

Patients and methods: This is a retrospective study of high risk (T(3), T(4), nodes positive, with or without margin involvement) post-operative esophageal cancer patients treated at London Regional Cancer Centre from 1989 to 1999. After esophagectomy, all patients received adjuvant combined modality therapy consisting of four cycles of fluorouracil-based chemotherapy, and loco-regional RT with or without coverage of the anastomotic site. RT dose ranged from 45 to 60 Gy at 1.8-2.0 Gy/fraction with treatment …

Subsets More Likely To Benefit From Surgery Or Prophylactic Cranial Irradiation After Chemoradiation For Localized Non-Small-Cell Lung Cancer, Bruce Keith, Mark Vincent, Larry Stitt, Anna Tomiak, Richard Malthaner, Edward Yu, Pauline Truong, Richard Inculet, Michael Lefcoe, A. Dar, Walter Kocha, Ian Craig

Richard A. Malthaner

After chemoradiation for localized non-small-cell lung cancer, surgery and prophylactic cranial irradiation (PCI) have been used as additional therapies. Less than a third of patients develop brain recurrences, or have local recurrence as their sole initial site of recurrence; these are groups that would benefit from PCI or surgery, respectively. Pretreatment identification of patients more likely to benefit from surgery or PCI would be useful. A retrospective analysis of 80 patients was performed to determine prognostic factors for such patterns of failure. Twenty-nine patients were subsequently selected for surgery in a nonrandomized manner. Seventeen patients had isolated local initial recurrence …

Management And Prognosis In Synchronous Solitary Resected Brain Metastasis From Non–Small-Cell Lung Cancer, Alexander Louie, George Rodrigues, Brian Yaremko, Edward Yu, A. Dar, Brian Dingle, Mark Vincent, Michael Sanatani, Richard Malthaner, Richard Inculet

Richard A. Malthaner

Background: Reports in the medical literature have described cases of extended survival of patients with non-small-cell lung cancer (NSCLC) with solitary metastatic disease who have received aggressive treatment both to the brain metastasis and to the local/regional disease. The objective of this research is to analyze prognostic factors that predict for outcome in this unique patient population.

Patients and methods: A single-institution, retrospective chart review was performed on 35 patients with NSCLC and a synchronous solitary brain metastasis (SSBM) treated with craniotomy and whole-brain radiation therapy. Eight patients (22.9%) had chest surgery, 24 (68.6%) had chemotherapy, and 14 (40%) had …

Subsets More Likely To Benefit From Surgery Or Prophylactic Cranial Irradiation After Chemoradiation For Localized Non-Small-Cell Lung Cancer, Bruce Keith, Mark Vincent, Larry Stitt, Anna Tomiak, Richard Malthaner, Edward Yu, Pauline Truong, Richard Inculet, Michael Lefcoe, A. Dar, Walter Kocha, Ian Craig

Richard A. Malthaner

After chemoradiation for localized non-small-cell lung cancer, surgery and prophylactic cranial irradiation (PCI) have been used as additional therapies. Less than a third of patients develop brain recurrences, or have local recurrence as their sole initial site of recurrence; these are groups that would benefit from PCI or surgery, respectively. Pretreatment identification of patients more likely to benefit from surgery or PCI would be useful. A retrospective analysis of 80 patients was performed to determine prognostic factors for such patterns of failure. Twenty-nine patients were subsequently selected for surgery in a nonrandomized manner. Seventeen patients had isolated local initial recurrence …

Long-Term Oncological Outcomes Of A Phase Ii Trial Of Neoadjuvant Chemohormonal Therapy Followed By Radical Prostatectomy For Patients With Clinically Localised, High-Risk Prostate Cancer., Jonathan L. Silberstein, Stephen A. Poon, Daniel D. Sjoberg, Alexandra C. Maschino, Andrew J. Vickers, Aaron Bernie, Badrinath R. Konety, William Kevin Kelly, James A. Eastham

Department of Urology Faculty Papers

OBJECTIVE: To determine long-term oncological outcomes of radical prostatectomy (RP) after neoadjuvant chemohormonal therapy (CHT) for clinically localised, high-risk prostate cancer.

PATIENTS AND METHODS: In this phase II multicentre trial of patients with high-risk prostate cancer (PSA level >20 ng/mL, Gleason ≥8, or clinical stage ≥T3), androgen-deprivation therapy (goserelin acetate depot) and paclitaxel, carboplatin and estramustine were administered before RP. We report the long-term oncological outcomes of these patients and compared them to a contemporary cohort who met oncological inclusion criteria but received RP only.

RESULTS: In all, 34 patients were enrolled and followed for a median of 13.1 years. …

Risk Analysis Of Prostate Cancer In Practical, A Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci., Ali Amin Al Olama, Sara Benlloch, Antonis C Antoniou, Graham G Giles, Gianluca Severi, David E Neal, Freddie C Hamdy, Jenny L Donovan, Kenneth Muir, Johanna Schleutker, Brian E Henderson, Christopher Haiman, Fredrick R Schumacher, Nora Pashayan, Paul D P Pharoah, Elaine A Ostrander, Janet L Stanford, Jyotsna Batra, Judith A Clements, Suzanne K Chambers, Maren Weischer, Børge G Nordestgaard, Sue A Ingles, Karina D Sorensen, Torben F Orntoft, Jong Y Park, Cezary Cybulski, Christiane Maier, Thilo Doerk, Joanne L Dickinson, Lisa Cannon-Albright, Hermann Brenner, Timothy R Rebbeck, Charnita Zeigler-Johnson, Tomonori Habuchi, Stephen N Thibodeau, Kathleen A Cooney, Pierre O Chappuis, Pierre Hutter, Radka P Kaneva, William D Foulkes, Maurice P Zeegers, Yong-Jie Lu, Hong-Wei Zhang, Robert Stephenson, Angela Cox, Melissa C Southey, Amanda B Spurdle, Liesel Fitzgerald, Daniel Leongamornlert, Edward Saunders, Malgorzata Tymrakiewicz, Michelle Guy, Tokhir Dadaev, Sarah J Little, Koveela Govindasami, Emma Sawyer, Rosemary Wilkinson, Kathleen Herkommer, John L Hopper, Aritaya Lophatonanon, Antje E Rinckleb, Zsofia Kote-Jarai, Rosalind A Eeles, Douglas F Easton

Department of Medical Oncology Faculty Papers

BACKGROUND: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer.

METHODS: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history.

RESULTS: The prostate cancer risk for men in the top 1% of the …

Comparison Of Survival In Patients With T Cell Lymphoma After Autologous And Allogeneic Stem Cell Transplantation As A Frontline Strategy Or In Relapsed Disease., Amer Beitinjaneh, Rima M. Saliba, L. Jeffrey Medeiros, Francesco Turturro, Gabriela Rondon, Martin Korbling, Luis Fayad, Michelle A. Fanale, Amin M. Alousi, Paolo Anderlini, Oran Betul, Uday R. Popat, Barbara Pro, Issa F. Khouri

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

We studied the roles of autologous (A) and allogeneic (allo) stem cell transplantation (SCT) in the treatment of 134 patients with T cell lymphoma (TCL) at our center. For frontline SCT, 58 patients were studied. The 4-year overall survival (OS) rates for ASCT (n = 47; median age, 49 years) and alloSCT (n = 11; median age, 55 years) groups were 76% and 54%, respectively (P > .05). The 4-year OS rates for first complete remission (CR1) patients were 84% and 83%, respectively. For SCT for relapsed disease, 76 patients were studied (41 with ASCT and 35 with alloSCT). The 4-year …

Plasma Tnf-Α And Soluble Tnf Receptor Levels After Doxorubicin With Or Without Co-Administration Of Mesna-A Randomized, Cross-Over Clinical Study, John Hayslip, Emily Van Meter Dressler, Heidi L. Weiss, Tammy J. Taylor, Mara D. Chambers, Teresa Noel, Sumitra Miriyala, Jeriel T. R. Keeney, Xiaojia Ren, Rukhsana Sultana, Mary Vore, D. Allan Butterfield, Daret St. Clair, Jeffrey A. Moscow

Markey Cancer Center Faculty Publications

PURPOSE: Chemotherapy-induced cognitive impairment (CICI) is a common sequelae of cancer therapy. Recent preclinical observations have suggested that CICI can be mediated by chemotherapy-induced plasma protein oxidation, which triggers TNF-α mediated CNS damage. This study evaluated sodium-2-mercaptoethane sulfonate (Mesna) co-administration with doxorubicin to reduce doxorubicin-induced plasma protein oxidation and resultant cascade of TNF-α, soluble TNF receptor levels and related cytokines.

METHODS: Thirty-two evaluable patients were randomized using a crossover design to receive mesna or saline in either the first or second cycle of doxorubicin in the context of a standard chemotherapy regimen for either non-Hodgkin lymphoma or breast …

African American Men With Low-Grade Prostate Cancer Have Increased Disease Recurrence After Prostatectomy Compared With Caucasian Men., Kosj Yamoah, Curtiland Deville, Neha Vapiwala, Elaine Spangler, Charnita M. Zeigler-Johnson, Bruce Malkowicz, David I Lee, Michael Kattan, Adam P. Dicker, Timothy R. Rebbeck

Department of Radiation Oncology Faculty Papers

PURPOSE: To explore whether disparities in outcomes exist between African American (AA) and Caucasian (CS) men with low-grade prostate cancer and similar cancer of the prostate risk assessment-postsurgery (CAPRA-S) features following prostatectomy (RP).

METHODS: The overall cohort consisted of 1,265 men (234 AA and 1,031 CS) who met the National comprehensive cancer network criteria for low- to intermediate-risk prostate cancer and underwent RP between 1990 and 2012. We first evaluated whether clinical factors were associated with adverse pathologic outcomes and freedom from biochemical failure (FFbF) using the entire cohort. Next, we studied a subset of 705 men (112 AA and …

Early Toxicity Predicts Long-Term Survival In High-Grade Glioma., Y. R. Lawrence, M Wang, Adam Dicker, David W Andrews, Walter J Curran, J M Michalski, L Souhami, W-Ka Yung, M Mehta

Yaacov R. Lawrence

BACKGROUND: Patients with high-grade gliomas are treated with surgery followed by chemoradiation. The risk factors and implications of neurological side effects are not known.

METHODS: Acute and late ≥ grade 3 neurological toxicities (NTs) were analysed among 2761 patients from 14 RTOG trials accrued from 1983 to 2003. The association between acute and late toxicity was analysed using a stepwise logistic regression model. The association between the occurrence of acute NT and survival was analysed as an independent variable.

RESULTS: There were 2610 analysable patients (86% glioblastoma, 10% anaplastic astrocytoma). All received a systemic agent during radiation (83% chemotherapy, 17% …

Splenic Infarction: An Update On William Osler's Observations., Yaacov R Lawrence, Ma Mbbs Mrcp, Russell Pokroy, Mb Bch, Daniel Berlowitz, Mb Bch, Dvora Aharoni, Md, Daniel Hain, Md, Gabriel S Breuer, Md

Yaacov R. Lawrence

BACKGROUND: Osler taught that splenic infarction presents with left upper abdominal quadrant pain, tenderness and swelling accompanied by a peritoneal friction rub. Splenic infarction is classically associated with bacterial endocarditis and sickle cell disease. OBJECTIVES: To describe the contemporary experience of splenic infarction. METHODS: We conducted a chart review of inpatients diagnosed with splenic infarction in a Jerusalem hospital between 1990 and 2003. RESULTS: We identified 26 cases with a mean age of 52 years. Common causes were hematologic malignancy (six cases) and intracardiac thrombus (five cases). Only three cases were associated with bacterial endocarditis. In 21 cases the splenic …

Targeted Mutational Profiling Of Peripheral T-Cell Lymphoma Not Otherwise Specified Highlights New Mechanisms In A Heterogeneous Pathogenesis., J. H. Schatz, S. M. Horwitz, J. Teruya-Feldstein, Matthew A. Lunning, A. Viale, K. Huberman, N. D. Socci, N. Lailler, A. Heguy, I. Dolgalev, J. C. Migliacci, M. Pirun, M. L. Palomba, D. M. Weinstock, H-G Wendel

Journal Articles: Oncology and Hematology

No abstract provided.

Clinical Significance Of A Point Mutation In Dna Polymerase Beta (Polb) Gene In Gastric Cancer., Xiaohui Tan, Hongyi Wang, Guangbin Luo, Shuyang Ren, Wenmei Li, Jiantao Cui, Harindarpal S. Gill, Sidney W. Fu, Youyong Lu

Medicine Faculty Publications

Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal …