Medicine and Health Sciences Commons^™

Pomalidomide, Dexamethasone, And Daratumumab In Relapsed Refractory Multiple Myeloma After Lenalidomide Treatment., David S Siegel, Gary J Schiller, Christy Samaras, Michael Sebag, Jesus Berdeja, Siddhartha Ganguly, Jeffrey Matous, Kevin Song, Christopher S Seet, Giampaolo Talamo, Mirelis Acosta-Rivera, Michael Bar, Donald Quick, Bertrand Anz, Gustavo Fonseca, Donna Reece, William E Pierceall, Weiyuan Chung, Faiza Zafar, Amit Agarwal, Nizar J Bahlis

Articles, Abstracts, and Reports

Patients with multiple myeloma who have relapsed after or become refractory to lenalidomide in early treatment lines represent a clinically important population in need of effective therapies. The safety and efficacy of pomalidomide, low-dose dexamethasone, and daratumumab was evaluated in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM) after one to two prior treatment lines in the phase 2 MM-014 study. Patients received pomalidomide 4 mg daily from days 1-21 and dexamethasone 40 mg weekly (28-day cycles). Daratumumab 16 mg/kg was administered per label. Primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. …

Long Term Survival And Local Control Outcomes From Single Dose Targeted Intraoperative Radiotherapy During Lumpectomy (Targit-Iort) For Early Breast Cancer: Targit-A Randomised Clinical Trial., Jayant S Vaidya, Max Bulsara, Michael Baum, Frederik Wenz, Samuele Massarut, Steffi Pigorsch, Michael Alvarado, Michael Douek, Christobel Saunders, Henrik L Flyger, Wolfgang Eiermann, Chris Brew-Graves, Norman R Williams, Ingrid Potyka, Nicholas Roberts, Marcelle Bernstein, Douglas Brown, Elena Sperk, Siobhan Laws, Marc Sütterlin, Tammy Corica, Steinar Lundgren, Dennis R Holmes, Lorenzo Vinante, Fernando Bozza, Montserrat Pazos, Magali Le Blanc-Onfroy, Günther Gruber, Wojciech Polkowski, Konstantin J Dedes, Marcus Niewald, Jens Blohmer, David Mccready, Richard Hoefer, Pond Kelemen, Gloria Petralia, Mary Falzon, David J Joseph, Jeffrey S Tobias

Articles, Abstracts, and Reports

OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer.

DESIGN: Prospective, open label, randomised controlled clinical trial.

SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada.

PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT).

INTERVENTIONS: …

Oral Cancer: Clinicopathological Features And Associated Risk Factors In A High Risk Population Presenting To A Major Tertiary Care Center In Pakistan, Namrah Anwar, Shahid Pervez, Qurratulain Chundriger, Mohammad Sohail Awan, Tariq Moatter, Tazeen Saeed Ali

Department of Pathology and Laboratory Medicine

Oral squamous cell carcinoma (OSCC) has the highest prevalence in head and neck cancers and is the first and second most common cancer in males and females of Pakistan respectively. Major risk factors include peculiar chewing habits like areca nut, betel quid, and tobacco. The majority of OSCC presents at an advanced stage with poor prognosis. On the face of such a high burden of this preventable cancer, there is a relative lack of recent robust data and its association with known risk factors from Pakistan. The aim of this study was to identify the socioeconomic factors and clinicopathological features …

Covid-19 Medical Papers Have Fewer Women First Authors Than Expected., Jens Peter Andersen, Mathias Wullum Nielsen, Nicole L Simone, Resa E Lewiss, Reshma Jagsi

Department of Radiation Oncology Faculty Papers

The COVID-19 pandemic has resulted in school closures and distancing requirements that have disrupted both work and family life for many. Concerns exist that these disruptions caused by the pandemic may not have influenced men and women researchers equally. Many medical journals have published papers on the pandemic, which were generated by researchers facing the challenges of these disruptions. Here we report the results of an analysis that compared the gender distribution of authors on 1893 medical papers related to the pandemic with that on papers published in the same journals in 2019, for papers with first authors and last …

Beyond An Updated Graded Prognostic Assessment (Breast Gpa): A Prognostic Index And Trends In Treatment And Survival In Breast Cancer Brain Metastases From 1985 To Today, Paul W Sperduto, Shane Mesko, Jing Li, Daniel Cagney, Ayal Aizer, Nancy U Lin, Eric Nesbit, Tim J Kruser, Jason Chan, Steve Braunstein, Jessica Lee, John P Kirkpatrick, Will Breen, Paul D Brown, Diana Shi, Helen A Shih, Hany Soliman, Arjun Sahgal, Ryan Shanley, William Sperduto, Emil Lou, Ashlyn Everett, Drexell Hunter Boggs, Laura Masucci, David Roberge, Jill Remick, Kristin Plichta, John M Buatti, Supriya Jain, Laurie E Gaspar, Cheng-Chia Wu, Tony J C Wang, John Bryant, Michael Chuong, James Yu, Veronica Chiang, Toshimichi Nakano, Hidefumi Aoyama, Minesh P Mehta

Journal Articles

PURPOSE: Brain metastases are a common sequelae of breast cancer. Survival varies widely based on diagnosis-specific prognostic factors (PF). We previously published a prognostic index (Graded Prognostic Assessment [GPA]) for patients with breast cancer with brain metastases (BCBM), based on cohort A (1985-2007, n = 642), then updated it, reporting the effect of tumor subtype in cohort B (1993-2010, n = 400). The purpose of this study is to update the Breast GPA with a larger contemporary cohort (C) and compare treatment and survival across the 3 cohorts.

METHODS AND MATERIALS: A multi-institutional (19), multinational (3), retrospective database of 2473 …

Protein-Altering Germline Mutations Implicate Novel Genes Related To Lung Cancer Development., Xuemei Ji, Semanti Mukherjee, Maria Teresa Landi, Yohan Bosse, Philippe Joubert, Dakai Zhu, Ivan Gorlov, Xiangjun Xiao, Younghun Han, Olga Gorlova, Rayjean J Hung, Yonathan Brhane, Robert Carreras-Torres, David C Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, Chu Chen, Jinyoung Byun, Konstantin H Dragnev, John K Field, Lambertus Fa Kiemeney, Philip Lazarus, Shan Zienolddiny, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Pier A Bertazzi, Angela C Pesatori, Nancy Diao, Li Su, Lei Song, Ruyang Zhang, Natasha Leighl, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher Haiman, Lynne Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Erik H F M Van Der Heijden, Jin Hee Kim, Michael P A Davies, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Gary E Goodman, Angela Cox, Fiona Taylor, Penella Woll, Erich Wichmann, Thomas Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances Shepherd, Ming-Sound Tsao, Susanne M Arnold, Eric B Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Lesley M Butler, Kenneth Offit, Preethi Srinivasan, Chaitanya Bandlamudi, Matthew D Hellmann, David B Solit, Mark E Robson, Charles M Rudin, Zsofia K Stadler, Barry S Taylor, Michael F Berger, Richard Houlston, John Mclaughlin, Victoria Stevens, David C Nickle, Ma'en Obeidat, Wim Timens, María Soler Artigas, Sanjay Shete, Hermann Brenner, Stephen Chanock, Paul Brennan, James D Mckay, Christopher I Amos

Articles, Abstracts, and Reports

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10-15) and replication (adjusted OR = 2.93, P = 2.22 × 10-3) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is …

Effect Of Pembrolizumab Plus Neoadjuvant Chemotherapy On Pathologic Complete Response In Women With Early-Stage Breast Cancer: An Analysis Of The Ongoing Phase 2 Adaptively Randomized I-Spy2 Trial., Rita Nanda, Minetta C Liu, Christina Yau, Rebecca Shatsky, Lajos Pusztai, Anne Wallace, A Jo Chien, Andres Forero-Torres, Erin D Ellis, Heather Han, Amy Clark, Kathy Albain, Judy C Boughey, Nora T Jaskowiak, Anthony Elias, Claudine Isaacs, Kathleen Kemmer, Teresa Helsten, Melanie Majure, Erica Stringer-Reasor, Catherine Parker, Marie C Lee, Tufia Haddad, Ronald N Cohen, Smita Asare, Amy Wilson, Gillian L Hirst, Ruby Singhrao, Katherine Steeg, Adam Asare, Jeffrey B Matthews, Scott Berry, Ashish Sanil, Richard Schwab, W Fraser Symmans, Laura Van 'T Veer, Douglas Yee, Angela Demichele, Nola M Hylton, Michelle Melisko, Jane Perlmutter, Hope S Rugo, Donald A Berry, Laura J Esserman

Articles, Abstracts, and Reports

Importance: Approximately 25% of patients with early-stage breast cancer who receive (neo)adjuvant chemotherapy experience a recurrence within 5 years. Improvements in therapy are greatly needed.

Objective: To determine if pembrolizumab plus neoadjuvant chemotherapy (NACT) in early-stage breast cancer is likely to be successful in a 300-patient, confirmatory randomized phase 3 neoadjuvant clinical trial.

Design, Setting, and Participants: The I-SPY2 study is an ongoing open-label, multicenter, adaptively randomized phase 2 platform trial for high-risk, stage II/III breast cancer, evaluating multiple investigational arms in parallel. Standard NACT serves as the common control arm; investigational agent(s) are added to this backbone. Patients with …

Randomized Phase Ii Study Of Stereotactic Body Radiotherapy And Interleukin-2 Versus Interleukin-2 In Patients With Metastatic Melanoma., Brendan Curti, Marka R Crittenden, Steven K Seung, Christopher B Fountain, Roxanne Payne, Shuching Chang, Jessica Fleser, Kimberly Phillips, Ian Malkasian, Lyn B Dobrunick, Walter Urba

Articles, Abstracts, and Reports

BACKGROUND: A pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL-2) showed a higher than anticipated objective response rate (ORR) among patients with metastatic melanoma (MM). We performed a prospective randomized study to determine if the ORR of SBRT + IL-2 was greater than IL-2 monotherapy in patients with advanced melanoma.

METHODS: Patients with MM who had adequate physiological reserve for IL-2 and at least one site suitable for SBRT were eligible. There was a 1:1 randomization to SBRT + IL-2 or IL-2 monotherapy. Patients received one or two doses of SBRT (20 Gy per fraction) …

Targeting The Tumor Core: Hypoxia-Responsive Nanoparticles For The Delivery Of Chemotherapy To Pancreatic Tumors, Matthew I. Confeld, Babak Mamnoon, Li Feng, Heather Jensen Smith, Priyanka Ray, James Froberg, Jiha Kim, Michael A. Hollingsworth, Mohiuddin Quadir, Yongki Choi, Sanku Mallik

Journal Articles: Eppley Institute

In pancreatic ductal adenocarcinoma (PDAC), early onset of hypoxia triggers remodeling of the extracellular matrix, epithelial-to-mesenchymal transition, increased cell survival, the formation of cancer stem cells, and drug resistance. Hypoxia in PDAC is also associated with the development of collagen-rich, fibrous extracellular stroma (desmoplasia), resulting in severely impaired drug penetration. To overcome these daunting challenges, we created polymer nanoparticles (polymersomes) that target and penetrate pancreatic tumors, reach the hypoxic niches, undergo rapid structural destabilization, and release the encapsulated drugs. In vitro studies indicated a high cellular uptake of the polymersomes and increased cytotoxicity of the drugs under hypoxia compared to …

Transcriptional And Immunohistological Assessment Of Immune Infiltration In Pancreatic Cancer., Brady Bernard, Venkatesh Rajamanickam, Christopher Dubay, Brian D. Piening, Emilio Alonso, Zeljka Jutric, Ephraim Tang, Pippa Newell, Paul D Hansen, Terry R Medler, Andrew J Gunderson, Kristina H Young, Carlo Bifulco, Joanna Pucilowska, Marka R Crittenden, Michael J. Gough

Articles, Abstracts, and Reports

Pancreatic adenocarcinoma is characterized by a complex tumor environment with a wide diversity of infiltrating stromal and immune cell types that impact the tumor response to conventional treatments. However, even in this poorly responsive tumor the extent of T cell infiltration as determined by quantitative immunohistology is a candidate prognostic factor for patient outcome. As such, even more comprehensive immunophenotyping of the tumor environment, such as immune cell type deconvolution via inference models based on gene expression profiling, holds significant promise. We hypothesized that RNA-Seq can provide a comprehensive alternative to quantitative immunohistology for immunophenotyping pancreatic cancer. We performed RNA-Seq …

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 …