Medicine and Health Sciences Commons^™

Autologous Cell Immunotherapy (Igv-001) With Igf-1r Antisense Oligonucleotide In Newly Diagnosed Glioblastoma Patients, Ian Y. Lee, Simon Hanft, Michael Schulder, Kevin D. Judy, Eric T. Wong, J. Bradley Elder, Linton T. Evans, Mario Zuccarello, Julian Wu, Sonikpreet Aulakh, Vijay Agarwal, Rohan Ramakrishna, Brian J. Gill, Alfredo Quiñones-Hinojosa, Cameron Brennan, Brad E. Zacharia, Carlos Eduardo Silva Correia, Madhavi Diwanji, Gregory K. Pennock, Charles Scott, Raul Perez-Olle, David W. Andrews, John A. Boockvar

Department of Neurosurgery Faculty Papers

Standard-of-care first-line therapy for patients with newly diagnosed glioblastoma (ndGBM) is maximal safe surgical resection, then concurrent radiotherapy and temozolomide, followed by maintenance temozolomide. IGV-001, the first product of the Goldspire™ platform, is a first-in-class autologous immunotherapeutic product that combines personalized whole tumor-derived cells with an antisense oligonucleotide (IMV-001) in implantable biodiffusion chambers, with the intent to induce a tumor-specific immune response in patients with ndGBM. Here, we describe the design and rationale of a randomized, double-blind, phase IIb trial evaluating IGV-001 compared with placebo, both followed by standard-of-care treatment in patients with ndGBM. The primary end point is progression-free …

Association Of Social Deprivation With Survival In Younger Adult Patients With Aml: An Alliance Study, Melanie Rebechi, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

No abstract provided.

Association Of Radiotherapy Duration With Clinical Outcomes In Patients With Esophageal Cancer Treated In Nrg Oncology Trials: A Secondary Analysis Of Nrg Oncology Randomized Clinical Trials, Christopher L. Hallemeier, Jennifer Moughan, Michael G. Haddock, Arnold M. Herskovic, Bruce D. Minsky, Mohan Suntharalingam, Kenneth L. Zeitzer, Madhur K. Garg, Bruce D. Greenwald, Ritsuko U. Komaki, Lindsay L. Puckett, Hyun Kim, Shane Lloyd, David A. Bush, Harold E. Kim, Thomas E. Lad, Joshua E. Meyer, Gordon S. Okawara, Adam Raben, Tracey E. Schefter, Jerry L. Barker, Carla I. Falkson, Gregory M.M. Videtic, Rojymon Jacob, Kathryn A. Winter, Christopher H. Crane

Einstein Health Papers

IMPORTANCE: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes.

OBJECTIVE: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT).

DESIGN, SETTING, AND PARTICIPANTS: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology …

Association Of Radiotherapy Duration With Clinical Outcomes In Patients With Esophageal Cancer Treated In Nrg Oncology Trials: A Secondary Analysis Of Nrg Oncology Randomized Clinical Trials, Christopher L Hallemeier, Hyun Kim, Et Al.

2020-Current year OA Pubs

IMPORTANCE: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes.

OBJECTIVE: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT).

DESIGN, SETTING, AND PARTICIPANTS: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology …

Is Local Review Of Positron Emission Tomography Scans Sufficient In Diffuse Large B-Cell Lymphoma Clinical Trials? A Calgb 50303 Analysis, Pallawi Torka, Levi D Pederson, Michael V Knopp, David Poon, Jun Zhang, Brad S Kahl, Howard R Higley, Gary Kelloff, Jonathan W Friedberg, Lawrence H Schwartz, Wyndham H Wilson, John P Leonard, Nancy L Bartlett, Heiko Schöder, Amy S Ruppert

2020-Current year OA Pubs

BACKGROUND: Quantitative methods of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) interpretation, including the percent change in FDG uptake from baseline (ΔSUV), are under investigation in lymphoma to overcome challenges associated with visual scoring systems (VSS) such as the Deauville 5-point scale (5-PS).

METHODS: In CALGB 50303, patients with DLBCL received frontline R-CHOP or DA-EPOCH-R, and although there were no significant associations between interim PET responses assessed centrally after cycle 2 (iPET) using 5-PS with progression-free survival (PFS) or overall survival (OS), there were significant associations between central determinations of iPET ∆SUV with PFS/OS. In this patient cohort, we retrospectively compared local …

Treatment Outcomes And Roles Of Transplantation And Maintenance Rituximab In Patients With Previously Untreated Mantle Cell Lymphoma: Results From Large Real-World Cohorts, Peter Martin, Jonathon B Cohen, Michael Wang, Anita Kumar, Brian Hill, Diego Villa, Jeffrey M Switchenko, Brad Kahl, Kami Maddocks, Natalie S Grover, Keqin Qi, Lori Parisi, Katherine Daly, Angeline Zhu, Gilles Salles

2020-Current year OA Pubs

PURPOSE: Commonly used first-line (1L) treatments for mantle cell lymphoma include high-dose cytarabine-based induction followed by autologous stem-cell transplant (ASCT) for younger patients and several chemoimmunotherapy regimens for older patients. Continuous debates exist on the role of ASCT in younger patients and maintenance rituximab (MR) after bendamustine plus rituximab (BR).

METHODS: Retrospective data from 4,216 patients with mantle cell lymphoma in the Flatiron Health electronic record-derived deidentified database diagnosed between 2011 and 2021, mostly in US community oncology settings, were evaluated for treatment patterns and outcomes. The efficacy findings with ASCT and MR were validated in an independent cohort of …

Postibrutinib Relapse Outcomes For Patients With Marginal Zone Lymphoma, Narendranath Epperla, Lauren Shea, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

No abstract provided.

Postibrutinib Relapse Outcomes For Patients With Marginal Zone Lymphoma, Narendranath Epperla, Qiuhong Zhao, Sayan Mullick Chowdhury, Lauren Shea, Tamara K. Moyo, Nishitha Reddy, Julia Sheets, David M. Weiner, Praveen Ramakrishnan Geethakumari, Malathi Kandarpa, Ximena Jordan Bruno, Colin Thomas, Michael C. Churnetski, Andrew Hsu, Luke Zurbriggen, Xiao-Wei Cherie Tan, Kathryn Lindsey, Joseph Maakaron, Paolo F. Caimi, Pallawi Torka, Celeste Bello, Sabarish Ayyappan, Timothy S. Oh, Reem Karmali, Seo-Hyun Kim, Anna Kress, Shalin Kothari, Yazeed Sawalha, Beth Christian, Kevin A. David, Irl Brian Greenwell, Murali Janakiram, Vaishalee P. Kenkre, Adam J. Olszewski, Jonathon B. Cohen, Neil Palmisiano, Elvira Umyarova, Ryan A. Wilcox, Farrukh T. Awan, Juan Pablo Alderuccio, Stefan K. Barta, Natalie S. Grover, Nilanjan Ghosh, Nancy L. Bartlett, Alex F. Herrera, Geoffrey Shouse

Department of Medicine Faculty Papers

No abstract provided.

Identification Of Patients With Ovarian Cancer Experiencing The Highest Benefit From Bevacizumab In The First-Line Setting On The Basis Of Their Tumor-Intrinsic Chemosensitivity (Kelim): The Gog-0218 Validation Study, Benoit You, David Mutch, Et Al.

2020-Current year OA Pubs

PURPOSE: In patients with high-grade ovarian cancer, predictors of bevacizumab efficacy in first-line setting are needed. In the ICON-7 trial, a poor tumor intrinsic chemosensitivity (defined by unfavorable modeled cancer antigen-125 [CA-125] ELIMination rate constant K [KELIM] score) was a predictive biomarker. Only the patients with high-risk disease (suboptimally resected stage III, or stage IV) exhibiting unfavorable KELIM score < 1.0 had overall survival (OS) benefit from bevacizumab (median: 29.7

METHODS: In GOG-0218, 1,873 patients were treated with carboplatin-paclitaxel ± concurrent-maintenance bevacizumab/placebo. Patient KELIM values were calculated with CA-125 kinetics during the first 100 chemotherapy days by the Lyon University team. The association between KELIM score (favorable ≥ 1.0, or unfavorable …

Overall Survival With Brentuximab Vedotin In Stage Iii Or Iv Hodgkin's Lymphoma, Stephen M Ansell, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

BACKGROUND: Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available.

METHODS: We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has …

Preoperative Magnetic Resonance Imaging In Locoregional Breast Cancer, Franklin Aldecoa Bedoya, Maritza Placencia Medina

Revista de la Facultad de Medicina Humana

Introduction. The use of preoperative magnetic resonance imaging (PMR) in patients with breast cancer is debatable, with little agreement on its usefulness above routine scans. The goal of this study was to assess comparative studies of individuals with non-advanced breast cancer who were treated with or without PMR. Methods. A search was conducted in MEDLINE/PUBMED, LILACS, and SCIELO for medical literature published between January 1, 2000 and March 31, 2021, and publications that satisfied the inclusion criteria were included. Results. There were 3,828 publications, 53 of which matched the inclusion requirements; the papers were examined, and the findings were summarized …

A Systematic Review Of Higher-Risk Myelodysplastic Syndromes Clinical Trials To Determine The Benchmark Of Azacitidine And Explore Alternative Endpoints For Overall Survival, Jacqueline S Garcia, Ronan T Swords, Gail J Roboz, Meagan A Jacoby, Guillermo Garcia-Manero, Wan-Jen Hong, Xiaoqing Yang, Ying Zhou, Uwe Platzbecker, David P Steensma, Johannes E Wolff, Pierre Fenaux

2020-Current year OA Pubs

The hypomethylating agent azacitidine can prolong overall survival (OS) in patients with higher risk-myelodysplastic syndromes (HR-MDS) compared to conventional regimens. However, outcomes differ largely between studies, making it challenging to determine the contribution of novel therapies added to azacitidine. Further, a discrepancy is seen between complete (CR) or partial (PR) response rates and OS improvement with azacitidine, making it challenging to rely on earlier endpoints than OS. We conducted a systematic literature search and study-level systematic review of 237 clinical studies to better understand outcomes for HR-MDS patients treated with azacitidine. Pooled marrow CR was 9% (N = 2654; 95% …

Neoadjuvant Anti-Ox40 (Medi6469) Therapy In Patients With Head And Neck Squamous Cell Carcinoma Activates And Expands Antigen-Specific Tumor-Infiltrating T Cells., Rebekka Duhen, Carmen Ballesteros-Merino, Alexandra K Frye, Eric Tran, Venkatesh Rajamanickam, Shu-Ching Chang, Yoshinobu Koguchi, Carlo Bifulco, Brady Bernard, Rom Leidner, Brendan Curti, Bernard A Fox, Walter Urba, Richard Bryan Bell, Andrew D Weinberg

Articles, Abstracts, and Reports

Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity in tumor-bearing hosts. Here we describe the results from a phase Ib clinical trial (NCT02274155) in which 17 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) received a murine anti-human OX40 agonist antibody (MEDI6469) prior to definitive surgical resection. The primary endpoint was to determine safety and feasibility of the anti-OX40 neoadjuvant treatment. The secondary objective was to assess the effect of …

Carfilzomib, Lenalidomide, And Dexamethasone Plus Transplant In Newly Diagnosed Multiple Myeloma, Jagoda K Jasielec, Ravi Vij, Et Al.

2020-Current year OA Pubs

In this phase 2 multicenter study, we evaluated the incorporation of autologous stem cell transplantation (ASCT) into a carfilzomib-lenalidomide-dexamethasone (KRd) regimen for patients with newly diagnosed multiple myeloma (NDMM). Transplant-eligible patients with NDMM received 4 cycles of KRd induction, ASCT, 4 cycles of KRd consolidation, and 10 cycles of KRd maintenance. The primary end point was rate of stringent complete response (sCR) after 8 cycles of KRd with a predefined threshold of ≥50% to support further study. Seventy-six patients were enrolled with a median age of 59 years (range, 40-76 years), and 35.5% had high-risk cytogenetics. The primary end point …

Prospective Molecular Profiling Of Circulating Tumor Cells From Patients With Melanoma Receiving Combinatorial Immunotherapy., Selena Y Lin, Shu-Ching Chang, Stella Lam, Romela Irene Ramos, Kevin Tran, Shuichi Ohe, Matthew P Salomon, Ali Asgar S Bhagat, Chwee Teck Lim, Trevan D Fischer, Leland J Foshag, Christine L Boley, Steven J O'Day, Dave Hoon

Articles, Abstracts, and Reports

BACKGROUND: Blood molecular profiling of circulating tumor cells (CTCs) can enable monitoring of patients with metastatic melanoma during checkpoint inhibitor immunotherapy (CII) and in combination with targeted therapies. We developed a microfluidics-based CTC platform to explore CTC profiling utility in CII-treated patients with melanoma using a melanoma messenger RNA (mRNA)/DNA biomarker panel.

METHODS: Blood samples (n = 213) were collected prospectively from 75 American Joint Committee on Cancer-staged III/IV melanoma patients during CII treatment and those enriched for CTCs. CTC profiling was performed using 5 known melanoma mRNA biomarkers and BRAF V600E DNA mutation. CTC biomarker status associations with clinical …

Outcomes Of Hematopoietic Cell Transplantation In Patients With Germline Samd9/Samd9l Mutations., Ibrahim A. Ahmed, Midhat S. Farooqi, Mark T. Vander Lugt, Jessica Boklan, Melissa Rose, Erika D. Friehling, Brandon Triplett, Kenneth Lieuw, Blachy Davila Saldana, Christine M. Smith, Jason R. Schwartz, Rakesh K. Goyal

Manuscripts, Articles, Book Chapters and Other Papers

Germline mutations in SAMD9 and SAMD9L genes cause MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) (OMIM: *610456) and ataxia-pancytopenia (OMIM: *611170) syndromes, respectively, and are associated with chromosome 7 deletions, myelodysplastic syndrome (MDS), and bone marrow failure. In this retrospective series, we report outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with hematologic disorders associated with SAMD9/SAMD9L mutations. Twelve patients underwent allogeneic HCT for MDS (n = 10), congenital amegakaryocytic thrombocytopenia (n = 1), and dyskeratosis congenita (n = 1). Exome sequencing revealed heterozygous mutations in SAMD9 (n = 6) or SAMD9L (n = …

A High-Throughput Screen Indicates Gemcitabine And Jak Inhibitors May Be Useful For Treating Pediatric Aml, Christina D. Drenberg, Anang Shelat, Jinjun Dang, Anitria Cotton, Shelley J. Orwick, Mengyu Li, Jae Yoon Jeon, Qiang Fu, Daelynn R. Buelow, Marissa Pioso, Shuiying Hu, Hiroto Inaba, Raul C. Ribeiro, Jeffrey E. Rubnitz, Tanja A. Gruber, R. Kiplin Guy, Sharyn D. Baker

Pharmaceutical Sciences Faculty Publications

Improvement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed to the development of better treatment regimens. High risk subtypes continue to have poor outcomes with event free survival rates < 40% despite the use of high intensity chemotherapy in combination with hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, and in vivo efficacy studies to identify therapeutic strategies for pediatric AML. We report therapeutics not currently used to treat AML, gemcitabine and cabazitaxel, have broad anti-leukemic activity across subtypes and are more effective relative to the AML standard of care, cytarabine, both in vitro and in vivo. JAK inhibitors are selective for acute megakaryoblastic leukemia and significantly prolong survival in multiple preclinical models. Our approach provides advances in the development of treatment strategies for pediatric AML.

Comparative Effectiveness Of Intensity Modulated Radiation Therapy To 3-Dimensional Conformal Radiation In Locally Advanced Lung Cancer: Pathological And Clinical Outcomes., Sarit Appel, Jair Bar, Alon Ben-Nun, Marina Perelman, Dror Alezra, Damien Urban, Maoz Ben-Ayun, Nir Honig, Efrat Ofek, Tamar Katzman, Amir Onn, Sumit Chatterji, Sergey Dubinski, Lev Tsvang, Shira Felder, Judith Kraitman, Ory Haisraely, Tatiana Rabin Alezra, Sivan Lieberman, Edith M. Marom, Nir Golan, David Simansky, Zvi Symon, Yaacov Richard Lawrence

Department of Radiation Oncology Faculty Papers

OBJECTIVE: Intensity-modulated radiotherapy (IMRT) has better normal-tissue sparing compared with 3-dimensional conformal radiation (3DCRT). We sought to assess the impact of radiation technique on pathological and clinical outcomes in locally advanced non-small cell lung cancer (LANSCLC) treated with a trimodality strategy.

METHODS: Retrospective review of LANSCLC patients treated from August 2012 to August 2018 at Sheba Medical Center, Israel. The trimodality strategy consisted of concomitant chemoradiation to 60 Gray (Gy) followed by completion surgery. The planning target volume (PTV) was defined by co-registered PET/CT. Here we compare the pathological regression, surgical margin status, local control rates (LC), disease free (DFS) …

Effect Of Aspirin On Disability-Free Survival In The Healthy Elderly, John J Mcneil, Robyn L Woods, Mark R Nelson, Christopher M Reid, Brenda Kirpach, Rory Wolfe, Elsdon Storey, Raj C Shah, Jessica E Lockery, Andrew M Tonkin, Anne B Newman, Jeff D Williamson, Karen L Margolis, Michael E Ernst, Walter P Abhayaratna, Nigel Stocks, Sharyn M Fitzgerald, Suzanne G Orchard, Ruth E Trevaks, Lawrence J Beilin, Geoffrey A Donnan, Peter Gibbs, Colin I Johnston, Joanne Ryan, Barbara Radziszewska, Richard Grimm, Anne M Murray

Journal Articles

BACKGROUND: Information on the use of aspirin to increase healthy independent life span in older persons is limited. Whether 5 years of daily low-dose aspirin therapy would extend disability-free life in healthy seniors is unclear.

METHODS: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or physical disability. Participants were randomly assigned to receive 100 mg per day of enteric-coated aspirin or placebo orally. The primary end …

Age Adjusted Hematopoietic Stem Cell Transplant Comorbidity Index Predicts Survival In A T-Cell Depleted Cohort, Hayder Saeed, Swati Yalamanchi, Meng Liu, Emily Van Meter, Zartash Gul, Gregory Monohan, Dianna Howard, Gerhard C. Hildebrandt, Roger Herzig

Markey Cancer Center Faculty Publications

Objectives: Allogeneic hematopoietic stem cell transplant (HCT) continues to evolve with the treatment in higher risk patient population. This practice mandates stringent update and validation of risk stratification prior to undergoing such a complex and potentially fatal procedure. We examined the adoption of the new comorbidity index (HCT-CI/Age) proposed by the Seattle group after the addition of age variable and compared it to the pre-transplant assessment of mortality (PAM) that already incorporates age as part of its evaluation criteria.

Methods: A retrospective analysis of adult patients who underwent HCT at our institution from January 2010 through August 2014 was …

Cetuximab Plus Carboplatin And Paclitaxel With Or Without Bevacizumab Versus Carboplatin And Paclitaxel With Or Without Bevacizumab In Advanced Nsclc (Swog S0819): A Randomised, Phase 3 Study, Roy S. Herbst, Mary W. Redman, Edward S. Kim, Thomas J. Semrad, Lyudmila Bazhenova, Gregory Masters, Kurt Oettel, Perry Guaglianone, Christopher Reynolds, Anand Karnad, Susanne M. Arnold, Marileila Varella-Garcia, James Moon, Philip C. Mack, Charles D. Blanke, Fred R. Hirsch, Karen Kelly, David R. Gandara

Markey Cancer Center Faculty Publications

Background

EGFR antibodies have shown promise in patients with advanced non-small-cell lung cancer (NSCLC), particularly with squamous cell histology. We hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH) can identify patients most likely to benefit from these drugs combined with chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy in patients with advanced NSCLC who are EGFR FISH-positive.

Methods

We did this open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico. We randomly assigned (1:1) eligible patients with treatment-naive stage IV NSCLC to receive paclitaxel (200 mg/m ²; every …

Ecog-Acrin (E4805) Randomized Phase Ii Study To Determine The Effect Of 2 Different Doses Of Aflibercept In Patients With Metastatic Renal Cell Carcinoma, Roberto Pili, Opeyemi Jegede, Michael A. Carducci, Judith Manola, David L. Groteluschen, Leonard L. Appleman, Glenn Liu, James C. Shanks, Shaker R. Dakhil, Janice Dutcher, Robert S. Dipaola

Internal Medicine Faculty Publications

Background—Aflibercept is a recombinantly-produced fusion protein that has potent anti-VEGF activity. We tested whether aflibercept has clinical activity in clear cell renal cell carcinoma (ccRCC). The recommended Phase 2 dose was 4 mg/kg but several patients treated at 1 mg/kg demonstrated prolonged progression-free survival (PFS). We therefore tested both doses in a parallel group randomized trial.

Methods—Eligible patients (pts) had histologically confirmed advanced or metastatic ccRCC and previous treatments including prior exposure to a VEGF RTKI. Patients received aflibercept (either 1 mg/kg or 4 mg/kg) day 1 of a 14-day cycle until progression. Patients randomized to 1 mg/kg …

Characterization Of Pulmonary Metastases In Children With Hepatoblastoma Treated On Children's Oncology Group Protocol Ahep0731 (The Treatment Of Children With All Stages Of Hepatoblastoma): A Report From The Children's Oncology Group., Allison F. O'Neill, Alexander J. Towbin, Mark D. Krailo, Caihong Xia, Yun Gao, M. Beth Mccarville, Rebecka L. Meyers, Eugene D. Mcgahren, Greg M. Tiao, Stephen P. Dunn, Max R. Langham, Christopher B. Weldon, Milton J. Finegold, Sarangarajan Ranganathan, Wayne L. Furman, Marcio Malogolowkin, Carlos Rodriguez-Galindo, Howard M. Katzenstein

Department of Pediatrics Faculty Papers

Purpose To determine whether the pattern of lung nodules in children with metastatic hepatoblastoma (HB) correlates with outcome. Methods Thirty-two patients with metastatic HB were enrolled on Children's Oncology Group Protocol AHEP0731 and treated with vincristine and irinotecan (VI). Responders to VI received two additional cycles of VI intermixed with six cycles of cisplatin/fluorouracil/vincristine/doxorubicin (C5VD), and nonresponders received six cycles of C5VD alone. Patients were imaged after every two cycles and at the conclusion of therapy. All computed tomography scans and pathology reports were centrally reviewed, and information was collected regarding lung nodule number, size, laterality, timing of resolution, and …

Association Of Disease Location And Treatment With Survival In Diffuse Large B-Cell Lymphoma Of The Eye And Ocular Adnexal Region., Aseef H H. Ahmed, C. Stephen Foster, Carol L. Shields

Wills Eye Hospital Papers

Importance: Primary diffuse large B-cell lymphoma (DLBCL) of the ocular region is rare, and the utility of surgery and radiation therapy remains unresolved.

Objective: To explore the clinical characteristics and determine factors associated with overall survival in primary vitreoretinal lymphoma (PVRL) and ocular adnexal (OA)-uveal DLBCL.

Design, Setting, and Participants: This retrospective analysis included 396 patients with ophthalmic DLBCL from January 1, 1973, through December 31, 2014, using the Surveillance, Epidemiology, and End Results database. The median follow-up was 39.0 months (interquartile range, 5.1-72.9 months). All patients diagnosed with primary DLBCL of the eye or retina (PVRL) or the eyelid, …

Effects Of Socioeconomic Status On Children With Well-Differentiated Thyroid Cancer., Evan F Garner, Ilan I Maizlin, Matthew B Dellinger, Kenneth W Gow, Melanie Goldfarb, Adam B Goldin, John J Doski, Monica Langer, Jed G Nuchtern, Sanjeev A Vasudevan, Mehul V Raval, Elizabeth A Beierle

Articles, Abstracts, and Reports

BACKGROUND: Well-differentiated thyroid cancer is the most common endocrine malignancy in children. Adult literature has demonstrated socioeconomic disparities in patients undergoing thyroidectomy, but the effects of socioeconomic status on the management of pediatric well-differentiated thyroid cancer remains poorly understood.

METHODS: Patients ≤21 years of age with well-differentiated thyroid cancer remains were reviewed from the National Cancer Data Base. Three socioeconomic surrogate variables were identified: insurance type, median income, and educational quartile. Tumor characteristics, diagnostic intervals, and clinical outcomes were compared within each socioeconomic surrogate variable.

RESULTS: A total of 9,585 children with well-differentiated thyroid cancer remains were reviewed. In multivariate …

Impact Of Time Between Diagnosis And Slnb On Outcomes In Cutaneous Melanoma., Daniel W Nelson, Stacey Stern, David E Elashoff, Robert Elashoff, John F Thompson, Nicola Mozzillo, Omgo E Nieweg, Harald J Hoekstra, Alistair J Cochran, Mark B Faries

Articles, Abstracts, and Reports

BACKGROUND: Hypothetically, delay between melanoma diagnosis and SLNB could affect outcomes, either adversely by allowing growth and dissemination of metastases, or beneficially by allowing development of an anti-melanoma immune response. Available data are conflicting about the effect of SLNB delay on patient survival. Our objective was to determine whether delay between initial diagnosis and SLNB affects outcomes in patients with cutaneous melanoma.

STUDY DESIGN: We performed query and analysis of a large prospectively maintained database of patients with primary cutaneous melanomas undergoing SLNB. An independent dataset from MSLT-1 (Multicenter Selective Lymphadenectomy Trial-1) was used for validation. Primary outcomes included disease-free …

Phase Ib/Ii Study Of The Safety And Efficacy Of Combination Therapy With Multikinase Vegf Inhibitor Pazopanib And Mek Inhibitor Trametinib In Advanced Soft Tissue Sarcoma., Vivek Subbiah, Christian Meyer, Ralph G. Zinner, Funda Meric-Bernstam, Marianna L. Zahurak, Ashley O'Connor, Jason Roszik, Kenna Shaw, Joseph A. Ludwig, Razelle Kurzrock, Nilofe A. Azad

Department of Medical Oncology Faculty Papers

Purpose: Pazopanib, a multireceptor tyrosine kinase inhibitor targeting primarily VEGFRs1–3, is approved for advanced soft tissue sarcoma (STS) and renal cell cancer. Downstream of VEGFR, trametinib is an FDA-approved MEK inhibitor used for melanoma. We hypothesized that vertical pathway inhibition using trametinib would synergize with pazopanib in advanced STS. Experimental Design: In an open-label, multicenter, investigator-initiated National Comprehensive Cancer Network (NCCN)-sponsored trial, patients with metastatic or advanced STS received pazopanib 800 mg and 2 mg of trametinib continuously for 28-day cycles. The primary endpoint was 4-month progression-free survival (PFS). Secondary endpoints were overall survival, response rate, and disease control rate. …

Mismatch Repair Deficiency Predicts Response Of Solid Tumors To Pd-1 Blockade., Dung T Le, Jennifer N Durham, Kellie N Smith, Hao Wang, Bjarne R Bartlett, Laveet K Aulakh, Steve Lu, Holly Kemberling, Cara Wilt, Brandon S Luber, Fay Wong, Nilofer S Azad, Agnieszka A Rucki, Dan Laheru, Ross Donehower, Atif Zaheer, George A Fisher, Todd S Crocenzi, James J Lee, Tim F Greten, Austin G Duffy, Kristen K Ciombor, Aleksandra D Eyring, Bao H Lam, Andrew Joe, S Peter Kang, Matthias Holdhoff, Ludmila Danilova, Leslie Cope, Christian Meyer, Shibin Zhou, Richard M Goldberg, Deborah K Armstrong, Katherine M Bever, Amanda N Fader, Janis Taube, Franck Housseau, David Spetzler, Nianqing Xiao, Drew M Pardoll, Nickolas Papadopoulos, Kenneth W Kinzler, James R Eshleman, Bert Vogelstein, Robert A Anders, Luis A Diaz

Articles, Abstracts, and Reports

The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis …

Adjuvant Radiation Therapy, Androgen Deprivation, And Docetaxel For High-Risk Prostate Cancer Postprostatectomy: Results Of Nrg Oncology/Rtog Study 0621., Mark D. Hurwitz, Jonathan Harris, Oliver Sartor, Ying Xiao, Bobby Shayegan, Paul W. Sperduto, Kasra R. Badiozamani, Colleen A.F. Lawton, Eric M. Horwitz, Jeff M. Michalski, Kevin Roof, David C. Beyer, Qiang Zhang, Howard M. Sandler

Department of Radiation Oncology Faculty Papers

BACKGROUND: Phase 3 trials have demonstrated a benefit from adjuvant radiation therapy (ART) for men who have adverse factors at radical prostatectomy (RP). However, some patients have a high risk of progression despite ART. The role of systemic therapy with ART in this high-risk group remains to be defined.

METHODS: Patients who had either a post-RP prostate-specific antigen (PSA) nadir > 0.2 ng/mL and a Gleason score ≥7 or a PSA nadir ≤0.2 ng/mL, a Gleason score ≥8, and a pathologic tumor (pT) classification ≥ pT3 received 6 months of androgen-deprivation therapy (ADT) plus radiotherapy and 6 cycles of docetaxel. The …

Completion Dissection Or Observation For Sentinel-Node Metastasis In Melanoma., Mark B. Faries, John F. Thompson, Alistair J. Cochran, Robert H. Andtbacka, Nicola Mozzillo, Jonathan S. Zager, Tiina Jahkola, Tawnya L. Bowles, Alessandro Testori, Peter D. Beitsch, Harald J. Hoekstra, Marc Moncrieff, Christian Ingvar, Michel W.J.M. Wouters, Michael S. Sabel, Edward A. Levine, Doreen Agnese, Michael Henderson, Reinhard Dummer, Carlo R. Rossi, Rogerio I. Neves, Steven D. Trocha, Frances Wright, David R. Byrd, Maurice Matter, Eddy Hsueh, Alastair Mackenzie-Ross, Douglas B. Johnson, Patrick Terheyden, Adam C. Berger, Tara L. Huston, Jeffrey D. Wayne, B. Mark Smithers, Heather B. Neuman, Schlomo Schneebaum, Jeffrey E. Gershenwald, Charlotte E. Ariyan, Darius C. Desai, Lisa Jacobs, Kelly M. Mcmasters, Anja Gesierich, Peter Hersey, Steven D. Bines, John M. Kane, Richard J. Barth, Gregory Mckinnon, Jeffrey M. Farma, Erwin Schultz, Sergi Vidal-Sicart, Richard A. Hoefer, James M Lewis, Randall Scheri, Mark C. Kelley, Omgo E. Nieweg, R. Dirk Noyes, Dave S.B. Hoon, He-Jing Wang, David A. Elashoff, Robert M. Elashoff

Department of Surgery Faculty Papers

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear.

METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis.

RESULTS: Immediate completion …