Prevalence of High Tumor Mutational Burden and Association With Survival in Patients With Less Common Solid Tumors

Shao, Changxia; Li, Gerald; Huang, Lingkang; Pruitt, Scott K.; Castellanos, Emily; Frampton, Garrett M.; Carson, Kenneth R.; Snow, Tamara; Singal, Gaurav; Fabrizio, David; Alexander, Brian M.; Jin, Fan; Zhou, Wei

doi:10.1001/jamanetworkopen.2020.25109

Cited by 108 publications

(80 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The overall prevalence of TMB-H in this study was 15.5%, similar to that reported in the KEYNOTE-158 study. Also, in our study, NETs and biliary tumors had much higher TMB-H rates than that in the KEYNOTE-158 study (43.8% vs 29.3%, 25.5% vs 4.0%, respectively) ( 20 , 50 ). Given the high prevalence of TMB-H status in rare tumors, the effect of TMB on immunotherapy response in rare tumors deserves further exploration.…”

Section: Discussioncontrasting

confidence: 55%

Comprehensive Genomic Profiling of Rare Tumors in China: Routes to Immunotherapy

et al. 2021

View full text Add to dashboard Cite

Treatment options for rare tumors are limited, and comprehensive genomic profiling may provide useful information for novel treatment strategies and improving outcomes. The aim of this study is to explore the treatment opportunities of patients with rare tumors using immune checkpoint inhibitors (ICIs) that have already been approved for routine treatment of common tumors. We collected immunotherapy-related indicators data from a total of 852 rare tumor patients from across China, including 136 programmed cell death ligand-1 (PD-L1) expression, 821 tumors mutational burden (TMB), 705 microsatellite instability (MSI) and 355 human leukocyte antigen class I (HLA-I) heterozygosity reports. We calculated the positive rates of these indicators and analyzed the consistency relationship between TMB and PD-L1, TMB and MSI, and HLA-I and PD-L1. The prevalence of PD-L1 positive, TMB-H, MSI-, and HLA-I -heterozygous was 47.8%, 15.5%, 7.4%, and 78.9%, respectively. The consistency ratio of TMB and PD-L1, TMB and MSI, and HLA-I and PD-L1 was 54.8% (78/135), 87.3% (598/685), and 47.4% (54/114), respectively. The prevalence of the four indicators varied widely across tumors systems and subtypes. The probability that neuroendocrine tumors (NETs) and biliary tumors may benefit from immunotherapy is high, since the proportion of TMB-H is as high as 50% and 25.4% respectively. The rates of PD-L1 positivity, TMB-H and MSI-H in carcinoma of unknown primary (CUP) were relatively high, while the rates of TMB-H and MSI-H in soft tissue tumors were both relatively low. Our study revealed the distribution of immunotherapeutic indicators in patients with rare tumors in China. Comprehensive genomic profiling may offer novel therapeutic modalities for patients with rare tumors to solve the dilemma of limited treatment options.

show abstract

Section: Discussioncontrasting

confidence: 55%

Comprehensive Genomic Profiling of Rare Tumors in China: Routes to Immunotherapy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Cancer in adult humans typically has dozens to hundreds of mutations per case, while pediatric cancers usually have far fewer mutations per case ( 58 ). A commonly employed metric for describing the frequency of mutations in a given cancer case is the tumor mutational burden (TMB), represented by the number of mutations per Mb (megabase, i.e., one million DNA bases) ( 81 ). A recent review of over 100,000 human cancer cases across more than 500 cancer types revealed a wide TMB spectrum, ranging from 0 to over 1,000 mutations/Mb, with a median of 3.6 mutations/Mb and increasing with patient age ( 82 ).…”

Section: Fundamentals Of Cancer Genomicsmentioning

confidence: 99%

Horizons in Veterinary Precision Oncology: Fundamentals of Cancer Genomics and Applications of Liquid Biopsy for the Detection, Characterization, and Management of Cancer in Dogs

Chibuk¹,

Flory²,

Kruglyak³

et al. 2021

Front. Vet. Sci.

View full text Add to dashboard Cite

Cancer is the leading cause of death in dogs, in part because many cases are identified at an advanced stage when clinical signs have developed, and prognosis is poor. Increased understanding of cancer as a disease of the genome has led to the introduction of liquid biopsy testing, allowing for detection of genomic alterations in cell-free DNA fragments in blood to facilitate earlier detection, characterization, and management of cancer through non-invasive means. Recent discoveries in the areas of genomics and oncology have provided a deeper understanding of the molecular origins and evolution of cancer, and of the “one health” similarities between humans and dogs that underlie the field of comparative oncology. These discoveries, combined with technological advances in DNA profiling, are shifting the paradigm for cancer diagnosis toward earlier detection with the goal of improving outcomes. Liquid biopsy testing has already revolutionized the way cancer is managed in human medicine – and it is poised to make a similar impact in veterinary medicine. Multiple clinical use cases for liquid biopsy are emerging, including screening, aid in diagnosis, targeted treatment selection, treatment response monitoring, minimal residual disease detection, and recurrence monitoring. This review article highlights key scientific advances in genomics and their relevance for veterinary oncology, with the goal of providing a foundational introduction to this important topic for veterinarians. As these technologies migrate from human medicine into veterinary medicine, improved awareness and understanding will facilitate their rapid adoption, for the benefit of veterinary patients.

show abstract

“…Theoretically, a higher TMB should therefore increase the likelihood for tumor neo-antigen production and as such the probability for immune recognition and tumor cell killing [ 147 ]. Even though MPM is considered to have a low TMB [ 48 , 148 , 149 ], TMB has been assessed is some available studies of checkpoint inhibitors.…”

Section: Outstanding Issues and Other Therapeutic Considerationsmentioning

confidence: 99%

Emerging avenues in immunotherapy for the management of malignant pleural mesothelioma

Gray

2021

BMC Pulm Med

View full text Add to dashboard Cite

Background The role of immunotherapy in cancer is now well-established, and therapeutic options such as checkpoint inhibitors are increasingly being approved in many cancers such as non-small cell lung cancer (NSCLC). Malignant pleural mesothelioma (MPM) is a rare orphan disease associated with prior exposure to asbestos, with a dismal prognosis. Evidence from clinical trials of checkpoint inhibitors in this rare disease, suggest that such therapies may play a role as a treatment option for a proportion of patients with this cancer. Main text While the majority of studies currently focus on the established checkpoint inhibitors (CTLA4 and PD1/PDL1), there are many other potential checkpoints that could also be targeted. In this review I provide a synopsis of current clinical trials of immunotherapies in MPM, explore potential candidate new avenues that may become future targets for immunotherapy and discuss aspects of immunotherapy that may affect the clinical outcomes of such therapies in this cancer. Conclusions The current situation regarding checkpoint inhibitors in the management of MPM whilst encouraging, despite impressive durable responses, immune checkpoint inhibitors do not provide a long-term benefit to the majority of patients with cancer. Additional studies are therefore required to further delineate and improve our understanding of both checkpoint inhibitors and the immune system in MPM. Moreover, many new potential checkpoints have yet to be studied for their therapeutic potential in MPM. All these plus the existing checkpoint inhibitors will require the development of new biomarkers for patient stratification, response and also for predicting or monitoring the emergence of resistance to these agents in MPM patients. Other potential therapeutic avenues such CAR-T therapy or treatments like oncolytic viruses or agents that target the interferon pathway designed to recruit more immune cells to the tumor also hold great promise in this hard to treat cancer.

show abstract

Prevalence of High Tumor Mutational Burden and Association With Survival in Patients With Less Common Solid Tumors

Cited by 108 publications

References 32 publications

Comprehensive Genomic Profiling of Rare Tumors in China: Routes to Immunotherapy

Comprehensive Genomic Profiling of Rare Tumors in China: Routes to Immunotherapy

Horizons in Veterinary Precision Oncology: Fundamentals of Cancer Genomics and Applications of Liquid Biopsy for the Detection, Characterization, and Management of Cancer in Dogs

Emerging avenues in immunotherapy for the management of malignant pleural mesothelioma

Contact Info

Product

Resources

About