Medicine and Health Sciences Commons^™

Tp53 Abnormalities Correlate With Immune Infiltration And Associate With Response To Flotetuzumab Immunotherapy In Aml., Jayakumar Vadakekolathu, Catherine Lai, Stephen Reeder, Sarah E Church, Tressa Hood, Anbarasu Lourdusamy, Michael P Rettig, Ibrahim Aldoss, Anjali S Advani, John E Godwin, Matthew J Wieduwilt, Martha Arellano, John Muth, Tung On Yau, Farhad Ravandi, Kendra Sweet, Heidi Altmann, Gemma A Foulds, Friedrich Stölzel, Jan Moritz Middeke, Marilena Ciciarello, Antonio Curti, Peter J M Valk, Bob Löwenberg, Ivana Gojo, Martin Bornhäuser, John F Dipersio, Jan K Davidson-Moncada, Sergio Rutella

Articles, Abstracts, and Reports

Somatic TP53 mutations and 17p deletions with genomic loss of TP53 occur in 37% to 46% of acute myeloid leukemia (AML) with adverse-risk cytogenetics and correlate with primary induction failure, high risk of relapse, and dismal prognosis. Herein, we aimed to characterize the immune landscape of TP53-mutated AML and determine whether TP53 abnormalities identify a patient subgroup that may benefit from immunotherapy with flotetuzumab, an investigational CD123 × CD3 bispecific dual-affinity retargeting antibody (DART) molecule. The NanoString PanCancer IO360 assay was used to profile 64 diagnostic bone marrow (BM) samples from patients with TP53-mutated (n = 42) and TP53-wild-type (TP53-WT) …

Targeting Breast Cancer Metabolism With A Novel Inhibitor Of Mitochondrial Atp Synthesis., Myoung Sook Kim, Ramkishore Gernapudi, Yessenia Cedeño Cedeño, Brian M Polster, Ramon Martinez, Paul Shapiro, Santosh Kesari, Elmar Nurmemmedov, Antonino Passaniti

Articles, Abstracts, and Reports

Inhibitors of mitochondrial respiration and ATP synthesis may promote the selective killing of respiration-competent cancer cells that are critical for tumor progression. We previously reported that CADD522, a small molecule inhibitor of the RUNX2 transcription factor, has potential for breast cancer treatment. In the current study, we show that CADD522 inhibits mitochondrial oxidative phosphorylation by decreasing the mitochondrial oxygen consumption rate (OCR) and ATP production in human breast cancer cells in a RUNX2-independent manner. The enzyme activity of mitochondrial ATP synthase was inhibited by CADD522 treatment. Importantly, results from cellular thermal shift assays that detect drug-induced protein stabilization revealed that …

Tp53 Abnormalities Correlate With Immune Infiltration And Associate With Response To Flotetuzumab Immunotherapy In Aml., Jayakumar Vadakekolathu, Catherine Lai, Stephen Reeder, Sarah E Church, Tressa Hood, Anbarasu Lourdusamy, Michael P Rettig, Ibrahim Aldoss, Anjali S Advani, John E Godwin, Matthew J Wieduwilt, Martha Arellano, John Muth, Tung On Yau, Farhad Ravandi, Kendra Sweet, Heidi Altmann, Gemma A Foulds, Friedrich Stölzel, Jan Moritz Middeke, Marilena Ciciarello, Antonio Curti, Peter J M Valk, Bob Löwenberg, Ivana Gojo, Martin Bornhäuser, John F Dipersio, Jan K Davidson-Moncada, Sergio Rutella

Articles, Abstracts, and Reports

Somatic TP53 mutations and 17p deletions with genomic loss of TP53 occur in 37% to 46% of acute myeloid leukemia (AML) with adverse-risk cytogenetics and correlate with primary induction failure, high risk of relapse, and dismal prognosis. Herein, we aimed to characterize the immune landscape of TP53-mutated AML and determine whether TP53 abnormalities identify a patient subgroup that may benefit from immunotherapy with flotetuzumab, an investigational CD123 × CD3 bispecific dual-affinity retargeting antibody (DART) molecule. The NanoString PanCancer IO360 assay was used to profile 64 diagnostic bone marrow (BM) samples from patients with TP53-mutated (n = 42) and TP53-wild-type (TP53-WT) …

Navigating The Paradox Of Scarcity: The Case For Radiologist-Driven Care., Daniel A Ortiz, Kevin M Cregan, Join Y Luh, Taj M Kattapuram

Articles, Abstracts, and Reports

No abstract provided.

No Time To Die: The Consensus Immunoscore For Predicting Survival And Response To Chemotherapy Of Locally Advanced Colon Cancer Patients In A Multicenter International Study., Paolo A Ascierto, Francesco M Marincola, Bernard A Fox, Jérôme Galon

Articles, Abstracts, and Reports

The multicenter international Society for Immunotherapy of Cancer (SITC) study of the consensus Immunoscore demonstrated the prediction of survival and response to chemotherapy in 763 Stage III colon cancer (CC) patients. Similar Immunoscore groups were found in elderly patients, and densities of immune cells and intratumoral T-cell repertoire were not decreasing with age in the tumor microenvironment. In two independent cohorts, Immunoscore significantly predicted time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS), including within high-risk (T4 or N2) and low-risk (T1-3, N1) patients. In stratified Cox multivariable analysis for TTR, DFS, and OS, Immunoscore's association to outcomes …

Feasibility Of Treating High Grade Gliomas In Children With Tumor-Treating Fields: A Case Series., John Crawford, Marlon G Saria, Girish Dhall, Ashley Margol, Santosh Kesari

Articles, Abstracts, and Reports

Children diagnosed with high grade gliomas (HGG) have dismal prognoses and treatment options remain limited. Tumor treating fields (TTFields) in combination with temozolomide (TMZ) is approved for the treatment of newly diagnosed and recurrent glioblastoma (GBM) in adult patients. However, clinical experience with TTFields in the pediatric HGG population is lacking. This retrospective review of four clinical cases was undertaken to evaluate the feasibility of treating children diagnosed with HGG off-label with TTFields. Patients were evaluated for device compliance, safety, and outcome. Treatment with TTFields was delivered via four transducer arrays placed on the shaved scalp, which were connected to …

Society For Immunotherapy Of Cancer Clinical And Biomarkers Data Sharing Resource Document: Volume I-Conceptual Challenges., Sergio Rutella, Michael A Cannarile, Sacha Gnjatic, Bruno Gomes, Justin Guinney, Vaios Karanikas, Mohan Karkada, John M Kirkwood, Beatrix Kotlan, Giuseppe V Masucci, Els Meeusen, Anne Monette, Aung Naing, Vésteinn Thorsson, Nicholas Tschernia, Ena Wang, Daniel K Wells, Timothy L Wyant, Alessandra Cesano

Articles, Abstracts, and Reports

The sharing of clinical trial data and biomarker data sets among the scientific community, whether the data originates from pharmaceutical companies or academic institutions, is of critical importance to enable the development of new and improved cancer immunotherapy modalities. Through data sharing, a better understanding of current therapies in terms of their efficacy, safety and biomarker data profiles can be achieved. However, the sharing of these data sets involves a number of stakeholder groups including patients, researchers, private industry, scientific journals and professional societies. Each of these stakeholder groups has differing interests in the use and sharing of clinical trial …

Untargeted Longitudinal Analysis Of A Wellness Cohort Identifies Markers Of Metastatic Cancer Years Prior To Diagnosis., Andrew T Magis, Noa Rappaport, Matthew P Conomos, Gilbert S Omenn, Jennifer C Lovejoy, Leroy Hood, Nathan D Price

Articles, Abstracts, and Reports

We analyzed 1196 proteins in longitudinal plasma samples from participants in a commercial wellness program, including samples collected pre-diagnosis from ten cancer patients and 69 controls. For three individuals ultimately diagnosed with metastatic breast, lung, or pancreatic cancer, CEACAM5 was a persistent longitudinal outlier as early as 26.5 months pre-diagnosis. CALCA, a biomarker for medullary thyroid cancer, was hypersecreted in metastatic pancreatic cancer at least 16.5 months pre-diagnosis. ERBB2 levels spiked in metastatic breast cancer between 10.0 and 4.0 months pre-diagnosis. Our results support the value of deep phenotyping seemingly healthy individuals in prospectively inferring disease transitions.

Nivolumab In Advanced Hepatocellular Carcinoma: Safety Profile And Select Treatment-Related Adverse Events From The Checkmate 040 Study., Karen Julien, Hiu Tung Leung, Carmen Fuertes, Megumi Mori, Miao-Jen Wang, Jocelyn Teo, Lisa Weiss, Sara Hamilton, Holly Difebo, Yoon Jin Noh, Aralee Galway, Jane Koh, Edith Brutcher, Huanyu Zhao, Yun Shen, Marina Tschaika, Yue-Yun To

Articles, Abstracts, and Reports

BACKGROUND: CheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment-related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open-label CheckMate 040 study.

MATERIALS AND METHODS: Select TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose-escalation and -expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and …

The Society For Immunotherapy Of Cancer (Sitc) Clinical Practice Guideline On Immunotherapy For The Treatment Of Acute Leukemia., Michael M Boyiadzis, Ivan Aksentijevich, Daniel A Arber, John Barrett, Renier J Brentjens, Jill Brufsky, Jorge Cortes, Marcos De Lima, Stephen J Forman, Ephraim J Fuchs, Linda J Fukas, Steven D Gore, Mark R Litzow, Jeffrey S Miller, John M Pagel, Edmund K Waller, Martin S Tallman

Articles, Abstracts, and Reports

Acute leukemia is a constellation of rapidly progressing diseases that affect a wide range of patients regardless of age or gender. Traditional treatment options for patients with acute leukemia include chemotherapy and hematopoietic cell transplantation. The advent of cancer immunotherapy has had a significant impact on acute leukemia treatment. Novel immunotherapeutic agents including antibody-drug conjugates, bispecific T cell engagers, and chimeric antigen receptor T cell therapies have efficacy and have recently been approved by the US Food and Drug Administration (FDA) for the treatment of patients with acute leukemia. The Society for Immunotherapy of Cancer (SITC) convened a panel of …

Lenvatinib Plus Pembrolizumab In Patients With Advanced Endometrial Cancer., Vicky Makker, Matthew H Taylor, Carol Aghajanian, Ana Oaknin, James Mier, Allen L Cohn, Margarita Romeo, Raquel Bratos, Marcia S Brose, Christopher Disimone, Mark Messing, Daniel E Stepan, Corina E Dutcus, Jane Wu, Emmett V Schmidt, Robert Orlowski, Pallavi Sachdev, Robert Shumaker, Antonio Casado Herraez

Articles, Abstracts, and Reports

PURPOSE: Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors.

METHODS: Patients took lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks, in 3-week cycles. The primary end point was objective response rate (ORR) at 24 weeks (ORR

RESULTS: At data cutoff, 108 patients with previously treated endometrial carcinoma were enrolled, with a median follow-up of 18.7 months. The ORR

CONCLUSION: Lenvatinib plus pembrolizumab showed …

Perspectives In Melanoma: Meeting Report From The "Melanoma Bridge" (December 5th-7th, 2019, Naples, Italy)., Paolo A Ascierto, Igor Puzanov, Sanjiv S Agarwala, Christian Blank, Richard D Carvajal, Sandra Demaria, Reinhard Dummer, Marc Ernstoff, Soldano Ferrone, Bernard A Fox, Thomas F Gajewski, Claus Garbe, Patrick Hwu, Roger S Lo, Georgina V Long, Jason J Luke, Iman Osman, Michael A Postow, Ryan J Sullivan, Janis M Taube, Giorgio Trinchieri, Hassane M Zarour, Corrado Caracò, Magdalena Thurin

Articles, Abstracts, and Reports

The melanoma treatment landscape changed in 2011 with the approval of the first anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 checkpoint inhibitor and of the first BRAF-targeted monoclonal antibody, both of which significantly improved overall survival (OS). Since then, improved understanding of the tumor microenvironment (TME) and tumor immune-evasion mechanisms has resulted in new approaches to targeting and harnessing the host immune response. The approval of new immune and targeted therapies has further improved outcomes for patients with advanced melanoma and other combination modalities are also being explored such as chemotherapy, radiotherapy, electrochemotherapy and surgery. In addition, different strategies of drugs administration including …

Sequential Complications Of Hypercalcemia, Necrotizing Granulomatous Vasculitis, And Aplastic Anemia Occurring In One Patient With Angioimmunoblastic T-Cell Lymphoma., Sriman Swarup, Jonathan Kopel, Kyaw Zin Thein, Kaiser Tarafdar, Khatrina Swarup, Seshadri Thirumala, Donald P Quick

Articles, Abstracts, and Reports

In this case report of a patient with angioimmunoblastic T-cell lymphoma (AITL), we describe the occurrence of three sequential complications that have been reported uncommonly in this disease subtype. Firstly, the patient developed hypercalcemia due to elevated 1,25-didydroxyvitamin D. Although hypercalcemia in AITL is not rare (1-2% incidence), this case was unusual in that the complication developed when disease appeared stable and symptomatically, he was doing well otherwise. Hypercalcemia surprisingly resolved a few months later at a time when his disease appeared to be progressing. A year later, the patient presented with digital ischemia necessitating partial amputation of a finger. …

Neoantigen-Specific Cd4(+) T-Cell Response Is Critical For The Therapeutic Efficacy Of Cryo-Thermal Therapy, Peng Peng, Hong-Ming Hu, Ping Liu, Lisa X Xu

Articles, Abstracts, and Reports

Background: Traditional tumor thermal ablations, such as radiofrequency ablation (RFA) and cryoablation, can result in good local control of tumor, but traditional tumor thermal ablations are limited by poor long-term survival due to the failure of control of distal metastasis. Our previous studies developed a novel cryo-thermal therapy to treat the B16F10 melanoma mouse model. Long-term survival and T-cell-mediated durable antitumor immunity were achieved after cryo-thermal therapy, but whether tumor antigen-specific T-cells were augmented by cryo-thermal therapy was not determined.

Methods: The long-term antitumor therapeutic efficacy of cryo-thermal therapy was performed in B16F10 murine melanoma models. Splenocytes derived from mice …

Efficacy And Safety Of First-Line Avelumab In Patients With Advanced Non-Small Cell Lung Cancer: Results From A Phase Ib Cohort Of The Javelin Solid Tumor Study., Claire F Verschraegen, Guy Jerusalem, Edward F Mcclay, Nicholas Iannotti, Charles H Redfern, Jaafar Bennouna, Franklin L Chen, Karen Kelly, Janice Mehnert, John C Morris, Matthew H Taylor, David Spigel, Ding Wang, Hans Juergen Grote, Dongli Zhou, Neru Munshi, Marcis Bajars, James L Gulley

Articles, Abstracts, and Reports

INTRODUCTION: Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC).

METHODS: In a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks. Endpoints included best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

RESULTS: Overall, 156 patients were enrolled …

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: …

Molecular Profiling Of Melanoma Brain Metastases Compared To Primary Cutaneous Melanoma And To Extracranial Metastases., Gino K In, Kelsey Poorman, Michelle Saul, Steven O'Day, Jeffrey M Farma, Anthony J Olszanski, Michael S Gordon, Jacob S Thomas, Burton Eisenberg, Lawrence Flaherty, Amy Weise, Steven Daveluy, Geoffrey Gibney, Michael B Atkins, Ari Vanderwalde

Articles, Abstracts, and Reports

BACKGROUND: Brain metastases are a significant cause of mortality and morbidity for patients with melanoma. We hypothesize that the development of brain metastases may be explained by molecular heterogeneity between primary cutaneous melanoma (PCM) or extracranial (ECM) and brain (MBM) melanoma metastases.

MATERIALS AND METHODS: We compared next-generation sequencing, tumor mutational burden (TMB), and immunohistochemical staining for PD-L1 expression, among 132 MBM, 745 PCM, and 1190 ECM.

RESULTS: The most common genetic alterations among MBM included: BRAF (52.4%), NRAS (26.6%), CDKN2A (23.3%), NF1 (18.9%), TP53 (18%), ARID2 (13.8%), SETD2 (11.9%), and PBRM1 (7.5%). Four genes were found with higher frequency …

Incorporating Breast Cancer Recurrence Events Into Population-Based Cancer Registries Using Medical Claims: Cohort Study., Teresa A'Mar, J David Beatty, Catherine Fedorenko, Daniel Markowitz, Thomas Corey, Jane Lange, Stephen M Schwartz, Bin Huang, Jessica Chubak, Ruth Etzioni

Articles, Abstracts, and Reports

BACKGROUND: There is a need for automated approaches to incorporate information on cancer recurrence events into population-based cancer registries.

OBJECTIVE: The aim of this study is to determine the accuracy of a novel data mining algorithm to extract information from linked registry and medical claims data on the occurrence and timing of second breast cancer events (SBCE).

METHODS: We used supervised data from 3092 stage I and II breast cancer cases (with 394 recurrences), diagnosed between 1993 and 2006 inclusive, of patients at Kaiser Permanente Washington and cases in the Puget Sound Cancer Surveillance System. Our goal was to classify …

The Great Debate At 'Immunotherapy Bridge', Naples, December 5, 2019., Paolo A Ascierto, Carlo Bifulco, Jerome Galon, Claus Garbe, Samir N Khleif, Jennifer Mcquade, Kunle Odunsi, Hideho Okada, Chrystal M Paulos, Sergio A Quezada, Hussein A Tawbi, John Timmerman, Giorgio Trinchieri, Lisa H Butterfield, Igor Puzanov

Articles, Abstracts, and Reports

As part of the 2019 Immunotherapy Bridge congress (December 4-5, Naples, Italy), the Great Debate session featured counterpoint views from leading experts on six topical issues in immunotherapy today. These were the use of chimeric antigen receptor T cell therapy in solid tumors, whether the Immunoscore should be more widely used in clinical practice, whether antibody-dependent cellular cytotoxicity is important in the mode of action of anticytotoxic T-lymphocyte-associated protein 4 antibodies, whether the brain is immunologically unique or just another organ, the role of microbiome versus nutrition in affecting responses to immunotherapy, and whether chemotherapy is immunostimulatory or immunosuppressive. Discussion …

Inter-Tumor Heterogeneity-Melanomas Respond Differently To Gm-Csf-Mediated Activation., Adi Moshe, Sivan Izraely, Orit Sagi-Assif, Sapir Malka, Shlomit Ben-Menachem, Tsipi Meshel, Metsada Pasmanik-Chor, Dave Hoon, Isaac P Witz

Articles, Abstracts, and Reports

Granulocyte-monocyte colony stimulating factor (GM-CSF) is used as an adjuvant in various clinical and preclinical studies with contradictory results. These were attributed to opposing effects of GM-CSF on the immune or myeloid systems of the treated patients or to lack of optimal dosing regimens. The results of the present study point to inter-tumor heterogeneity as a possible mechanism accounting for the contrasting responses to GM-CSF incorporating therapies. Employing xenograft models of human melanomas in nude mice developed in our lab, we detected differential functional responses of melanomas from different patients to GM-CSF both in vitro as well as in vivo. …

Perianal Basal Cell Carcinoma: A Common Cancer In An Uncommon Location., Ed Hagen, Nathan Hite, John A Griffin, Rodney Kratz

Articles, Abstracts, and Reports

This is a case of a perianal basal cell carcinoma, a common skin cancer in an unusual location. Our patient is a 67-year-old male with a perianal lesion. He first noticed this painless lesion 5 years prior to presentation and was having fecal incontinence and weight loss. He had a fully encompassing ulcerated lesion involving the entirety of the anal margin. We performed a biopsy that returned on pathology as a basal cell carcinoma. Due to the size of the lesion and his current nutritional status, it was determined to be unresectable. We were able to provide him with a …

A Phase Ii Single-Arm Study Of Pembrolizumab With Enzalutamide In Men With Metastatic Castration-Resistant Prostate Cancer Progressing On Enzalutamide Alone., Julie N Graff, Tomasz M Beer, Joshi J Alumkal, Rachel E Slottke, William L. Redmond, George V Thomas, Reid F Thompson, Mary A Wood, Yoshinobu Koguchi, Yiyi Chen, Emile Latour, Raymond C Bergan, Charles G Drake, Amy E Moran

Articles, Abstracts, and Reports

BACKGROUND: Checkpoint inhibitors can induce profound anticancer responses, but programmed cell death protein-1 (PD-1) inhibition monotherapy has shown minimal activity in prostate cancer. A published report showed that men with prostate cancer who were resistant to the second-generation androgen receptor inhibitor enzalutamide had increased programmed death-ligand 1 (PD-L1) expression on circulating antigen-presenting cells. We hypothesized that the addition of PD-1 inhibition in these patients could induce a meaningful cancer response.

METHODS: We evaluated enzalutamide plus the PD-1 inhibitor pembrolizumab in a single-arm phase II study of 28 men with metastatic castration-resistant prostate cancer (mprogressing on enzalutamide alone. Pembrolizumab 200 mg …

Integrated Assessment Of Circulating Cell-Free Microrna Signatures In Plasma Of Patients With Melanoma Brain Metastasis., Matias Bustos, Kevin Tran, Negin Rahimzadeh, Rebecca Gross, Selena Y Lin, Yoshiaki Shoji, Tomohiro Murakami, Christine L Boley, Linh T Tran, Hunter Cole, Daniel F Kelly, Steven J O'Day, Dave Hoon

Articles, Abstracts, and Reports

Primary cutaneous melanoma frequently metastasizes to distant organs including the brain. Identification of cell-free microRNAs (cfmiRs) found in the blood can be used as potential body fluid biomarkers for detecting and monitoring patients with melanoma brain metastasis (MBM). In this pilot study, we initially aimed to identify cfmiRs in the blood of MBM patients. Normal donors plasma (healthy, n = 48) and pre-operative MBM patients' plasma samples (n = 36) were compared for differences in >2000 microRNAs (miRs) using a next generation sequencing (NGS) probe-based assay. A 74 cfmiR signature was identified in an initial cohort of MBM plasma …

Complex Oncological Decision-Making Utilizing Fast-And-Frugal Trees In A Community Setting-Role Of Academic And Hybrid Modeling., Ravi Salgia, Isa Mambetsariev, Tingting Tan, Amanda Schwer, Daryl Pearlstein, Hazem Chehabi, Angel Baroz, Jeremy Fricke, Rebecca Pharaon, Hannah Romo, Thomas Waddington, Razmig Babikian, Linda Buck, Prakash Kulkarni, Mary Cianfrocca, Benjamin Djulbegovic, Sumanta K Pal

Articles, Abstracts, and Reports

Non-small cell lung cancer is a devastating disease and with the advent of targeted therapies and molecular testing, the decision-making process has become complex. While established guidelines and pathways offer some guidance, they are difficult to utilize in a busy community practice and are not always implemented in the community. The rationale of the study was to identify a cohort of patients with lung adenocarcinoma at a City of Hope community site (n = 11) and utilize their case studies to develop a decision-making framework utilizing fast-and-frugal tree (FFT) heuristics. Most patients had stage IV (N = 9, 81.8%) disease …

Discrimination Of Benign From Malignant Breast Lesions In Dense Breasts With Model-Based Analysis Of Regions-Of-Interest Using Directional Diffusion-Weighted Images., Alan I Penn, Milica Medved, Vandana Dialani, Etta D Pisano, Elodia B Cole, David Brousseau, Gregory S Karczmar, Guimin Gao, Barry D Reich, Hiroyuki Abe

Articles, Abstracts, and Reports

BACKGROUND: There is an increasing interest in non-contrast-enhanced magnetic resonance imaging (MRI) for detecting and evaluating breast lesions. We present a methodology utilizing lesion core and periphery region of interest (ROI) features derived from directional diffusion-weighted imaging (DWI) data to evaluate performance in discriminating benign from malignant lesions in dense breasts.

METHODS: We accrued 55 dense-breast cases with 69 lesions (31 benign; 38 cancer) at a single institution in a prospective study; cases with ROIs exceeding 7.50 cm

RESULTS: The region-growing algorithm for 3D lesion model generation improved inter-observer variability over hand drawn ROIs (DSC: 0.66 vs 0.56 (p < 0.001) with substantial agreement (DSC > 0.8) …

Bilateral Pulmonary Metastases Of Papillary Thyroid Carcinoma In A 12-Year-Old Child-A Case Report And Review Of The Literature., V Thirumala, C O'Souji, S Thirumala

Articles, Abstracts, and Reports

Metastatic disease of the lung has been extensively documented in the adult patient population. The most common primary sources for pulmonary metastases include breast, colon gastrointestinal including pancreas and urinary bladder. Malignant lung tumors in pediatric population is extremely rare. However, like in adult patient population, metastases are more common than primary tumors in lung in pediatric patients. Metastatic spread of tumors can occur both by way of hematogenous spread and lymphatic pathways. We present a rare case of biopsy proven metastatic thyroid carcinoma in the lung in a 12-year-old male child masquerading as bilateral miliary nodules on imaging studies. …

Robotic Surgery For Gynecologic Cancers: Indications, Techniques And Controversies., Kiran H Clair, Krishnansu S Tewari

Articles, Abstracts, and Reports

Minimally invasive surgery for gynecologic cancers is associated with fewer postoperative complications including less blood loss and quicker recovery time compared to traditional laparotomy. The robotic platform has allowed patients access to minimally invasive surgery due to its increased utilization by gynecologic oncologists. Many surgeons have embraced the robotic platform due to its technological advances over traditional laparoscopy including high-definition 3D optics, wristed instrumentation, camera stability and improved ergonomics. While robotic surgery continues as a mainstay in the management of gynecologic cancers, it remains controversial in regards to its cost effectiveness and more recently, its long-term impact on clinical and …

Novel Application Of Vinylpolysiloxane Hearing Aid Impression Mold As Patient-Specific Bolus For Head And Neck Cancer Radiotherapy., Anne Elizabeth Gunter, John Burgoyne, Min Park, Namou Kim, Daliang Cao, Vivek Mehta

Articles, Abstracts, and Reports

Hearing aid impression material composed of vinylpolysiloxane is an ideal bolus material which may be used to aid in delivery of adjuvant radiation to complex surgical defects of the head and neck. It is affordable, easily accessed, and efficient.

Correction To: Small Molecule Kras Agonist For Mutant Kras Cancer Therapy., Ke Xu, Dongkyoo Park, Andrew T Magis, Jun Zhang, Wei Zhou, Gabriel L Sica, Suresh S Ramalingam, Walter J Curran, Xingming Deng

Articles, Abstracts, and Reports

An amendment to this paper has been published and can be accessed via the original article.

Allosteric Inhibitor Of Β-Catenin Selectively Targets Oncogenic Wnt Signaling In Colon Cancer., Anton Cheltsov, Natsuko Nomura, Venkata Mahidhar Yenugonda, Jatin Roper, Rajesh Mukthavaram, Pengfei Jiang, Nam-Gu Her, Ivan Babic, Santosh Kesari, Elmar Nurmemmedov

Articles, Abstracts, and Reports

Abnormal regulation of β-catenin initiates an oncogenic program that serves as a main driver of many cancers. Albeit challenging, β-catenin is an attractive drug target due to its role in maintenance of cancer stem cells and potential to eliminate cancer relapse. We have identified C2, a novel β-catenin inhibitor, which is a small molecule that binds to a novel allosteric site on the surface of β-catenin. C2 selectively inhibits β-catenin, lowers its cellular load and significantly reduces viability of β-catenin-driven cancer cells. Through direct binding to β-catenin, C2 renders the target inactive that eventually activates proteasome system for its removal. …