Oncology Commons^™

Atm Deficiency Confers Specific Therapeutic Vulnerabilities In Bladder Cancer, Yuzhen Zhou, Judit Börcsök, Elio Adib, Sophia C. Kamran, Alexander J. Neil, Konrad Stawiski, Dory Freeman, Dag Rune Stormoen, Zsofia Sztupinszki, Amruta Samant, Amin Nassar, Raie T. Bekele, Timothy Hanlon, Henkel Valentine, Ilana Epstein, Bijaya Sharma, Kristen Felt, Philip Abbosh, Chin-Lee Wu, Jason A. Efstathiou, David T. Miyamoto, William Anderson, Zoltan Szallasi, Kent W. Mouw

Einstein Health Papers

Ataxia-telangiectasia mutated (ATM) plays a central role in the cellular response to DNA damage and ATM alterations are common in several tumor types including bladder cancer. However, the specific impact of ATM alterations on therapy response in bladder cancer is uncertain. Here, we combine preclinical modeling and clinical analyses to comprehensively define the impact of ATM alterations on bladder cancer. We show that ATM loss is sufficient to increase sensitivity to DNA-damaging agents including cisplatin and radiation. Furthermore, ATM loss drives sensitivity to DNA repair-targeted agents including poly(ADP-ribose) polymerase (PARP) and Ataxia telangiectasia and Rad3 related (ATR) inhibitors. ATM loss …

Cellular Metabolism Therapy Slowing Growth Rate Of Glioblastomas, Heet Patel

Rowan-Virtua Research Day

Glioblastoma Multiforme (GBM), more commonly known as glioblastomas, are a form of specialized brain tumors called gliomas. Glioblastomas most commonly occur in glial cells of the central nervous system and the average age of diagnosis is 64. Treatment methods implemented currently are surgery of the removable masses followed by courses of chemotherapy and radiotherapy. These methods can only prolong the life span by a few months and as such, new research focused on tumor cell metabolism is being conducted to determine its impact on the progression of this tumor. Tumor masses, such as Glioblastomas, modify their metabolism via the Warburg …

Evaluating The Effect Of A Taxane-Based Anti-Cancer Drug On The Adult Taste Organ Using A Mouse Model, Archana Kumari, Lucre'ce Estropia

Rowan-Virtua Research Day

Chemosensory alteration is one of the major side effects of chemotherapy that can negatively impact the quality of life of cancer patients. Decreased appetite and food aversions can consequently lead to substantial reductions in food intake and thereby malnutrition and poor patient outcomes. The chemotherapeutic agent, taxane (docetaxel), is an effective choice of treatment for breast cancer, gastric cancer, or prostate cancer. Despite its major effects as an anti-cancer medication, patients under taxane treatments have reported taste alterations. Essentially, the drug disrupts normal microtubule growth by inhibiting microtubule depolymerization. By binding to ß-tubulin, a major component of mitotic spindles, docetaxel …

Mcl-1 Inhibition Modulates Erk-Mediated Resistance In Multiple Myeloma, Omar Al-Odat, Krishne Gowda, Shantu Amin, Tulin Budak-Alpdogan, Subash Jonnalagadda, Manoj Pandey

Rowan-Virtua Research Day

Novel multiple myeloma (MM) treatments have significantly improved over the previous several decades, primarily on account of targeting bone marrow microenvironment (BMM) pathways. However, drug resistance and patient relapse remain major clinical problems. The role of BMM in the upregulation of anti-apoptotic protein Mcl-1 is well documented. The Mcl-1 protein plays a critical role in the progression and acquired drug resistance in MM. The regulation of Mcl-1, a protein characterized by a short half-life, from transcription to degradation is crucial for understanding its role in cell survival. The GSK3β and Erk play important role in the stability of Mcl-1. Also, …

Cancer Stem Cell Assay-Guided Chemotherapy Improves Survival Of Patients With Recurrent Glioblastoma In A Randomized Trial, Tulika Ranjan, Soma Sengupta, Michael J. Glantz, Richard M. Green, Alexander Yu, Dawit Aregawi, Rekha Chaudhary, Ricky Chen, Mario Zuccarello, Christine Lu-Emerson, Hugh D. Moulding, Neil Belman, Jon Glass, Aaron Mammoser, Mark Anderson, Jagan Valluri, Nicholas Marko, Jason Schroeder, Steven Jubelirer, Frances Chow, Pier Paolo Claudio, Anthony M. Alberico, Seth T. Lirette, Krista L. Denning, Candace M. Howard

Department of Neurosurgery Faculty Papers

Therapy-resistant cancer stem cells (CSCs) contribute to the poor clinical outcomes of patients with recurrent glioblastoma (rGBM) who fail standard of care (SOC) therapy. ChemoID is a clinically validated assay for identifying CSC-targeted cytotoxic therapies in solid tumors.

In a randomized clinical trial (NCT03632135), the ChemoID assay, a personalized approach for selecting the most effective treatment from FDA-approved chemotherapies, improves the survival of patients with rGBM (2016 WHO classification) over physician-chosen chemotherapy. In the ChemoID assay-guided group, median survival is 12.5 months (95% confidence interval [CI], 10.2-14.7) compared with 9 months (95% CI, 4.2-13.8) in the physician-choice group (p = …

Nivolumab Plus Ipilimumab Versus Extreme Regimen As First-Line Treatment For Recurrent/Metastatic Squamous Cell Carcinoma Of The Head And Neck: The Final Results Of Checkmate 651., Robert I. Haddad, Kevin Harrington, Makoto Tahara, Robert L. Ferris, Maura Gillison, Jerome Fayette, Amaury Daste, Piotr Koralewski, Bogdan Zurawski, Miren Taberna, Nabil F. Saba, Milena Mak, Andrzej Kawecki, Gustavo Girotto, Miguel Angel Alvarez Avitia, Caroline Even, Joaquin Gabriel Reinoso Toledo, Alexander Guminski, Urs Müller-Richter, Naomi Kiyota, Mustimbo Roberts, Tariq Aziz Khan, Karen Miller-Moslin, Li Wei, Athanassios Argiris

Department of Medical Oncology Faculty Papers

Purpose: CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

Methods: Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and …

Geographic Variations And The Associated Factors In Adherence To And Persistence With Adjuvant Hormonal Therapy For The Privately Insured Women Aged 18-64 With Breast Cancer In Texas, Junghyun Kim, Man S Kim, Suja S Rajan, Xianglin L Du, Luisa Franzini, Tae Gi Kim, Sharon H Giordano, Robert O Morgan

Journal Articles

The purpose of this study is to examine the geographical patterns of adjuvant hormonal therapy adherence and persistence and the associated factors in insured Texan women aged 18-64 with early breast cancer. A retrospective cohort study was conducted using 5-year claims data for the population insured by the Blue Cross Blue Shield of Texas (BCBSTX). Women diagnosed with early breast cancer who were taking tamoxifen or aromatase inhibitors (AIs) for adjuvant hormonal therapy with at least one prescription claim were identified. Adherence to adjuvant hormonal therapy and persistence with adjuvant hormonal therapy were calculated as outcome measures. Women without a …

Geographic Variations And The Associated Factors In Adherence To And Persistence With Adjuvant Hormonal Therapy For The Privately Insured Women Aged 18-64 With Breast Cancer In Texas, Junghyun Kim, Man S Kim, Suja S Rajan, Xianglin L Du, Luisa Franzini, Tae Gi Kim, Sharon H Giordano, Robert O Morgan

Journal Articles

The purpose of this study is to examine the geographical patterns of adjuvant hormonal therapy adherence and persistence and the associated factors in insured Texan women aged 18-64 with early breast cancer. A retrospective cohort study was conducted using 5-year claims data for the population insured by the Blue Cross Blue Shield of Texas (BCBSTX). Women diagnosed with early breast cancer who were taking tamoxifen or aromatase inhibitors (AIs) for adjuvant hormonal therapy with at least one prescription claim were identified. Adherence to adjuvant hormonal therapy and persistence with adjuvant hormonal therapy were calculated as outcome measures. Women without a …

Antibody Therapies For The Treatment Of Acute Myeloid Leukemia: Exploring Current And Emerging Therapeutic Targets, Joshua W Morse, Margarita Rios, John Ye, Adan Rios, Cheng Cheng Zhang, Naval G Daver, Courtney D Dinardo, Ningyan Zhang, Zhiqiang An

Journal Articles

INTRODUCTION: Acute myeloid leukemia (AML) is the most common and deadly type of leukemia affecting adults. It is typically managed with rounds of non-targeted chemotherapy followed by hematopoietic stem cell transplants, but this is only possible in patients who can tolerate these harsh treatments and many are elderly and frail. With the identification of novel tumor-specific cell surface receptors, there is great conviction that targeted antibody therapies will soon become available for these patients.

AREAS COVERED: In this review, we describe the current landscape of known target receptors for monospecific and bispecific antibody-based therapeutics for AML. Here, we characterize each …

Chemotherapy-Induced Toxicities And Their Associations With Clinical And Non-Clinical Factors Among Breast Cancer Patients In Vietnam, Sang M Nguyen, Anh T Pham, Lan M Nguyen, Hui Cai, Thuan V Tran, Xiao-Ou Shu, Huong T T Tran

Journal Articles

Understanding the burden and factors related to chemotherapy-induced toxicity is important in treatment planning for breast cancer patients. We conducted a prospective study among 396 newly diagnosed and chemotherapy-treated breast cancer patients recruited in two major cancer hospitals in northern Vietnam. Toxicities were captured through medical chart reviews and patient self-reports and graded using NCI CTCAE classification. Associations for sociodemographic and clinical factors with chemotherapy-induced toxicities during first-line chemotherapy were evaluated via multivariable logistic regression. Severe (i.e., grade ≥ 3) hematological (38.6%), and gastrointestinal (12.9%) toxicities were common. A pre-existing nephrological condition was significantly associated with the risk of severe …

Tumor Treating Fields With Radiation For Glioblastoma: A Narrative Review, Ryan C. Miller, Muneeb Khan Niazi, Olga Russial, Spencer Poiset, Wenyin Shi

Department of Radiation Oncology Faculty Papers

Background and objective: With a phase 3 clinical trial (EF-32, ClinicalTrials.gov: NCT04471844) currently underway examining the potential benefit of concurrent chemoradiation and tumor treating fields (TTFields) for patients with glioblastoma (GBM), we present the following narrative review to highlight the current evidence that supports this approach. The current management paradigm for GBM includes maximal safe surgical resection followed by concurrent chemoradiation with further temozolomide (TMZ) and TTFields used as maintenance therapy. Despite several treatment advances over the past few decades, the overall prognosis remains poor and new strategies are currently under investigation, including the use of chemoradiation concurrently with …

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 …

Ramucirumab: A New Agent For Advanced Or Metastatic Gastric Junction Adenocarcinoma, Adam Smith, Rebecca Worden, Jessica Hoffert, Brendon Rasor, Hannah Stewart, David Koh

Pharmacy and Wellness Review

Ramucirumab (Cyramza®), approved April 21, 2014, is a vascular endothelial growth factor receptor 2 (VEGFR2) antagonist with a U.S. Food and Drug Administration (FDA) indication for the treatment of advanced or metastatic gastric/gastroesophageal junction adenocarcinoma. Gastric cancer is a prevalent cancer in the United States with a poor prognosis. The phase 3 trial, REGARD, shows that ramucirumab, when used within four months after the last dose of first-line chemotherapy or six months after the last dose of adjuvant chemotherapy, increases overall survival. Also, ramucirumab has been included in combination therapy, such as in the RAINBOW trial, which demonstrated its effectiveness …

Gilteritinib Or Chemotherapy For Relapsed Or Refractory Flt3-Mutated Aml, Alexander E. Perl, Giovanni Martinelli, Jorge E. Cortes, Andreas Neubauer, Ellin Berman, Stefania Paolini, Pau Montesinos, Maria R. Baer, Richard A. Larson, Celalettin Ustun, Francesco Fabbiano, Harry P. Erba, Antonio Di Stasi, Robert Stuart, Rebecca Olin, Margaret Kasner, Fabio Ciceri, Wen-Chien Chou, Nikolai Podoltsev, Christian Recher, Hisayuki Yokoyama, Naoko Hosono, Sung-Soo Yoon, Je-Hwan Lee, Timothy Pardee, Amir T. Fathi, Chaofeng Liu, Nahla Hasabou, Xuan Liu, Erkut Bahceci, Mark J. Levis

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (AML) with mutations in the FMS-like tyrosine kinase 3 gene (FLT3) infrequently have a response to salvage chemotherapy. Gilteritinib is an oral, potent, selective FLT3 inhibitor with single-agent activity in relapsed or refractory FLT3-mutated AML.

METHODS: In a phase 3 trial, we randomly assigned adults with relapsed or refractory FLT3-mutated AML in a 2:1 ratio to receive either gilteritinib (at a dose of 120 mg per day) or salvage chemotherapy. The two primary end points were overall survival and the percentage of patients who had complete remission …

Potential Use Of Dopamine And Dopamine Agonists As Angiogenesis Inhibitors In The Treatment Of Cancer, Benjamin Finley, Katherine Liu, Daniel Powell, Jamie Kellner, David H. Kinder

Pharmacy and Wellness Review

In recent years, there have been numerous developments in monoclonal antibodies used as anticancer drugs with a focus on reducing the ability of cancers to metastasize and produce new vasculature. These agents are called angiogenesis inhibitors and although these agents have been proven effective in treating certain types of cancers, production and administration of monoclonal antibodies comes at a steep cost with a severe side effect profile. Under normal physiologic conditions, angiogenesis is an important mechanism to create new blood vessels from preexisting vessels, usually occurring in adults. Tumor cells can hijack the angiogenesis pathway to produce new distant tumors …

Multiple Sclerosis Outcomes After Cancer Immunotherapy, Catherine R. Garcia, Rani Jayswal, Val R. Adams, Lowell B. Anthony, John L. Villano

Markey Cancer Center Faculty Publications

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes.

METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution.

RESULTS: We identified 14 cases of MS …

Neurological Improvement Of Perineural And Leptomeningeal Spread Of Squamous Cell Carcinoma Treated With Intrathecal Chemotherapy And Systemic Egfr Inhibition., Vincent Alexander Van Vugt, Marlon Garzo Saria, Andres Javier, Navin Kesari, Tiffany Turpin, Santosh Kesari

Marlon Garzo Saria, PhD, RN, AOCNS, FAAN

Squamous cell carcinoma (SCC) is a common cancer of the skin. Risk factors include fair skin, excessive sun and ultraviolet light exposure, and history of xeroderma pigmentosa. Perineural invasion (PNI), an uncommon manifestation of SCC, involves microscopic tumor cells invading various layers of the nerve sheath. It is associated with a poorer prognosis. Standard treatment for PNI includes radiation therapy. Here, we describe a case an older gentleman with a history of SCC with PNI successfully treated with erlotinib and intrathecal chemotherapy.

Inotuzumab Ozogamicin In Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia., Deepa Bhojwani, Richard Sposto, Nirali N. Shah, Vilmarie Rodriguez, Constance Yuan, Maryalice Stetler-Stevenson, Maureen M. O'Brien, Jennifer L. Mcneer, Amrana Quereshi, Aurelie Cabannes, Paul Schlegel, Claudia Rossig, Luciano Dalla-Pozza, Keith August, Sarah Alexander, Jean-Pierre Bourquin, Michel Zwaan, Elizabeth A. Raetz, Mignon L. Loh, Susan R. Rheingold

Manuscripts, Articles, Book Chapters and Other Papers

Although inotuzumab ozogamicin (InO) is recognized as an effective agent in relapsed acute lymphoblastic leukemia (ALL) in adults, data on safety and efficacy in pediatric patients are scarce. We report the use of InO in 51 children with relapsed/refractory ALL treated in the compassionate use program. In this heavily pretreated cohort, complete remission was achieved in 67% of patients with overt marrow disease. The majority (71%) of responders were negative for minimal residual disease. Responses were observed irrespective of cytogenetic subtype or number or type of prior treatment regimens. InO was well-tolerated; grade 3 hepatic transaminitis or hyperbilirubinemia were noted …

Buparlisib In Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase Ii Trial., Patrick Y Wen, Mehdi Touat, Brian M Alexander, Ingo K Mellinghoff, Shakti Ramkissoon, Christine S Mccluskey, Kristine Pelton, Sam Haidar, Sankha S Basu, Sarah C Gaffey, Loreal E Brown, Juan Emmanuel Martinez-Ledesma, Shaofang Wu, Jungwoo Kim, Wei Wei, Mi-Ae Park, Jason T Huse, John G Kuhn, Mikael L Rinne, Howard Colman, Nathalie Y R Agar, Antonio M Omuro, Lisa M Deangelis, Mark R Gilbert, John F De Groot, Timothy F Cloughesy, Andrew S Chi, Thomas M Roberts, Jean J Zhao, Eudocia Q Lee, Lakshmi Nayak, James R Heath, Laura L Horky, Tracy T Batchelor, Rameen Beroukhim, Susan M Chang, Azra H Ligon, Ian F Dunn, Dimpy Koul, Geoffrey S Young, Michael D Prados, David A Reardon, W K Alfred Yung, Keith L Ligon

Articles, Abstracts, and Reports

PURPOSE: Phosphatidylinositol 3-kinase (PI3K) signaling is highly active in glioblastomas. We assessed pharmacokinetics, pharmacodynamics, and efficacy of the pan-PI3K inhibitor buparlisib in patients with recurrent glioblastoma with PI3K pathway activation.

METHODS: This study was a multicenter, open-label, multi-arm, phase II trial in patients with PI3K pathway-activated glioblastoma at first or second recurrence. In cohort 1, patients scheduled for re-operation after progression received buparlisib for 7 to 13 days before surgery to evaluate brain penetration and modulation of the PI3K pathway in resected tumor tissue. In cohort 2, patients not eligible for re-operation received buparlisib until progression or unacceptable toxicity. Once …

Rare But Recurrent Ros1 Fusions Resulting From Chromosome 6q22 Microdeletions Are Targetable Oncogenes In Glioma., Monika A Davare, Jacob J Henderson, Anupriya Agarwal, Jacob P Wagner, Sudarshan R Iyer, Nameeta Shah, Randy Woltjer, Romel Somwar, Stephen W Gilheeney, Ana Decarvalo, Tom Mikkelson, Erwin G Van Meir, Marc Ladanyi, Brian J Druker

Articles, Abstracts, and Reports

PURPOSE: Gliomas, a genetically heterogeneous group of primary central nervous system tumors, continue to pose a significant clinical challenge. Discovery of chromosomal rearrangements involving kinase genes has enabled precision therapy, and improved outcomes in several malignancies.

EXPERIMENTAL DESIGN: Positing that similar benefit could be accomplished for patients with brain cancer, we evaluated The Cancer Genome Atlas (TCGA) glioblastoma dataset. Functional validation of the oncogenic potential and inhibitory sensitivity of discovered ROS1 fusions was performed using three independent cell-based model systems, and an

RESULTS:

CONCLUSIONS: Our findings highlight that CNS tumors should be specifically interrogated for these rare intrachromosomal 6q22 microdeletion …

Oncolog, Volume 63, Number 05-06, May - June 2018, Joe Munch, Sunita Patterson, Bryan Tutt

OncoLog MD Anderson's Report to Physicians (All issues)

• Breast Cancer Treatment without Surgery: New approach may let certain breast cancer patients who respond to systemic therapy forgo surgery
• INBRIEF: Targeted Drug BLU-667 Shows Promise against Solid Tumors with RET Alterations
• Diet May Improve Gut Microbiome in Colorectal Cancer Survivors: Trial tests whether adding beans to diet affects markers of cancer risk, metabolic health
• TRK Inhibition Shows Activity in Solid Tumors: Early results of clinical trials for adult, pediatric patients with NTRK gene fusions show promise
• HOUSE CALL: Preparing for Natural Disasters-People with cancer or other chronic illnesses should take extra precautions

Oncolog, Volume 63. Number 03, March 2018, Bryan Tutt

OncoLog MD Anderson's Report to Physicians (All issues)

• Local Consolidative Therapy Plus Immunotherapy or Targeted Agents for NSCLC: Clinical trials explore surgery/radiation plus immune checkpoint or tyrosine kinase inhibitors for metastatic non-small cell lung cancer
• INBRIEF: CAR T Cells Elicit Durable Responses in Large B Cell Lymphoma
• Managing Opioid Use in Cancer Patients: Vigilance and interventions ensure patient safety
• Hepatitis C Virus Linked to Head and Neck Cancers: Association of HCV with extrahepatic cancers has implications for HCV testing, treatment
• HOUSE CALL: Understanding cancer Risk and Risk factors-Your risk factors might affect your need for cancer screening

Oncolog, Volume 63, Number 01, January 2018, Bryan Tutt

OncoLog MD Anderson's Report to Physicians (All issues)

• Immunotherapy for Genitourinary Cancers: Clinical trials explore immune checkpoint inhibitors for bladder, kidney, prostate cancers
• Active Surveillance for Ductal Carcinoma in Situ: COMET trial compares frequent mammography to standard treatment with surgery
• Radiation Plus Chemotherapy for Nasal NK T Cell Lymphoma: Clinical trial may standardize treatment for rare cancer
• HOUSE CALL: Mammography Is Essential for Breast cancer Screening- FDA warns against clinics that advertise screening without mammography
• USEFULRESOURCES: Videoconferences Allow Collaboration in Cancer Prevention, Treatment, Survivorship

Tumor And Microenvironment Evolution During Immunotherapy With Nivolumab., Nadeem Riaz, Jonathan J Havel, Vladimir Makarov, Alexis Desrichard, Walter Urba, Jennifer S Sims, F Stephen Hodi, Salvador Martín-Algarra, Rajarsi Mandal, William H Sharfman, Shailender Bhatia, Wen-Jen Hwu, Thomas F Gajewski, Craig L Slingluff, Diego Chowell, Sviatoslav M Kendall, Han Chang, Rachna Shah, Fengshen Kuo, Luc G T Morris, John-William Sidhom, Jonathan P Schneck, Christine E Horak, Nils Weinhold, Timothy A Chan

Articles, Abstracts, and Reports

The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by whole-exome, transcriptome, and/or T cell receptor (TCR) sequencing. In responding patients, mutation and neoantigen load were reduced from baseline, and analysis of intratumoral heterogeneity during therapy demonstrated differential clonal evolution within tumors and putative selection against neoantigenic mutations on-therapy. Transcriptome analyses before and during nivolumab therapy revealed increases in distinct immune cell subsets, activation of specific …

Oncolog, Volume 62, Number 11-12, November - December 2017, Joe Munch, Bryan Tutt

OncoLog MD Anderson's Report to Physicians (All issues)

• Managing Chemotherapy-Induced Neuropathy: Neuromodulation, pharmacological treatments show promise against peripheral neuropathy in cancer patients.
• Treating Tobacco Addiction: MD Anderson provides pharmacotherapy, counseling to help smokers quit plus cessation education, resources for community practitioners
• HOUSE CALL: Smoking-Related Cancers- Cancer risks from tobacco are not limited to the lungs, but quitting reduces these risks

Efficacy And Safety Of Pembrolizumab In Patients Enrolled In Keynote-030 In The United States: An Expanded Access Program., Tara C Gangadhar, Wen-Jen Hwu, Michael A Postow, Omid Hamid, Adil Daud, Roxana Dronca, Richard Joseph, Steven J O'Day, F S Hodi, Anna C Pavlick, Harriet Kluger, Romina P Oxborough, Aiming Yang, Mihaela Gazdoiu, Debra A Kush, Scot Ebbinghaus, April K S Salama

Articles, Abstracts, and Reports

KEYNOTE-030 (ClinicalTrials.gov ID, NCT02083484) was a global expanded access program that allowed access to pembrolizumab, an antiprogrammed death 1 antibody, for patients with advanced melanoma before its regulatory approval. Patients with unresectable stage III/IV melanoma that progressed after standard-of-care therapy, including ipilimumab and, if BRAF mutant, a BRAF inhibitor, were eligible to receive pembrolizumab 2 mg/kg every 3 weeks. Response was assessed by immune-related response criteria by investigator review. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. In the United States, 979 patients enrolled between April and September 2014. …

Oncolog, Volume 62, Number 10, October 2017, Sarah Bronson, Bryan Tutt

OncoLog MD Anderson's Report to Physicians (All issues)

• Organ-Sparing Therapy for Esophageal Cancer: Endoscopic surgery, ablation treat early-stage cancer, dysplasia while avoiding esophagectomy.
• INBRIEF: Surgeons Perform Unique Allogeneic Soft Tissue Transplant Between Identical Twins
• Advances in Breast Reconstruction: New reconstruction techniques increase breast cancer surgical options, improve cosmetic outcomes.
• HOUSE CALL: Facing the Financial Burden of Cancer Treatment-Talking to care team, seeking out resources are important steps in managing cancer-related financial stress
• INBRIEF: Proton Therapy plus Chemotherapy Shows Promise in Lung Cancer Trial

Neurological Improvement Of Perineural And Leptomeningeal Spread Of Squamous Cell Carcinoma Treated With Intrathecal Chemotherapy And Systemic Egfr Inhibition., Vincent Alexander Van Vugt, Marlon Garzo Saria, Andres Javier, Navin Kesari, Tiffany Turpin, Santosh Kesari

Articles, Abstracts, and Reports

Squamous cell carcinoma (SCC) is a common cancer of the skin. Risk factors include fair skin, excessive sun and ultraviolet light exposure, and history of xeroderma pigmentosa. Perineural invasion (PNI), an uncommon manifestation of SCC, involves microscopic tumor cells invading various layers of the nerve sheath. It is associated with a poorer prognosis. Standard treatment for PNI includes radiation therapy. Here, we describe a case an older gentleman with a history of SCC with PNI successfully treated with erlotinib and intrathecal chemotherapy.

Ibrutinib Unmasks Critical Role Of Bruton Tyrosine Kinase In Primary Cns Lymphoma., Christian Grommes, Alessandro Pastore, Nicolaos Palaskas, Sarah S. Tang, Carl Campos, Derrek Schartz, Paolo Codega, Donna Nichol, Owen Clark, Wan-Ying Hsieh, Dan Rohle, Marc Rosenblum, Agnes Viale, Viviane S. Tabar, Cameron W. Brennan, Igor T. Gavrilovic, Thomas J. Kaley, Craig P. Nolan, Antonio Omuro, Elena Pentsova, Alissa A. Thomas, Elina Tsyvkin, Ariela Noy, M. Lia Palomba, Paul Hamlin, Craig S. Sauter, Craig H. Moskowitz, Julia Wolfe, Ahmet Dogan, Minhee Won, Jon Glass, Scott Peak, Enrico C. Lallana, Vaios Hatzoglou, Anne S. Reiner, Philip H. Gutin, Jason T. Huse, Katherine S. Panageas, Thomas G. Graeber, Nikolaus Schultz, Lisa M. Deangelis, Ingo K. Mellinghoff

Department of Neurology Faculty Papers

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor-associated …

Oncolog, Volume 62, Number 08, August 2017, Bryan Tutt, Sarah Bronson

OncoLog MD Anderson's Report to Physicians (All issues)

• Immunotherapy for Smoldering Myeloma: Clinical trials test PD-1, DC38 inhibitors to delay progression from premalignant disease to multiple myeloma.
• Malignant Pheochromocytoma and Sympathetic Paraganglioma Research: Studies may expand treatment options for patients with rare neuroendocrine tumors.
• Hypofractionated Partial-Breast Irradiation: Clinical trial tests 10-day external-beam radiation therapy regimen after lumpectomy for patients with early-stage breast cancer.
• HOUSE CALL: Support for Cancer Patients: Patients, caregivers find many types of support from various organizations