ABSTRACT
Endometrial cancer is the most common gynecologic malignancy in the U.S. and, although the majority of cases present at an early stage and can be treated with curative intent, those who present with advanced disease, or develop metastatic or recurrent disease, have a poorer prognosis. A subset of endometrial cancers exhibit mismatch repair (MMR) deficiency. It is now recognized that MMR-deficient cancers are particularly susceptible to programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, and in a landmark judgement in 2017, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab for these tumors, the first tumor-agnostic approval of a drug. However, less is known about the sensitivity to PD-1 blockade among patients with known mutations in double-strand break DNA repair pathways involving homologous recombination, such as those in BRCA1 or BRCA2. Here we report a case of a patient with an aggressive somatic MMR-deficient endometrial cancer and a germline BRCA1 who experienced a rapid complete remission to pembrolizumab. KEY POINTS: Endometrial cancers, and in particular endometrioid carcinomas, should undergo immunohistochemical testing for mismatch repair proteins.Uterine cancers with documented mismatch repair deficiency are candidates for treatment with programmed cell death protein 1 inhibition.Genomic testing of recurrent, advanced, or metastatic tumors may be useful to determine whether patients are candidates for precision therapies.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , BRCA1 Protein/genetics , DNA Mismatch Repair/genetics , Germ-Line Mutation/genetics , Adult , Antibodies, Monoclonal, Humanized/pharmacology , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/pathology , Female , Humans , Remission InductionABSTRACT
PURPOSE OF REVIEW: The current article reviews the advances and challenges in the fight with cancer and the hope for cure, with a focus on clinical trials, at the one time with the best outcomes; first-line therapy. RECENT FINDINGS: To date there have been four great stories that bridge inception to development of new drugs in ovarian cancer: Serendipitous insight into the role of platinum, discovery of taxanes, understanding the microenvironment and angiogenesis, and following the science in the development of Poly (ADP-Ribose) Polymerase (PARP) inhibitors. There is a fundamental difference between overall survival (OS), simply living longer; and eradicating disease, cure. The scientific underpinning of both our understanding and the recent developments encourages an optimistic view of the remaining hurdles. SUMMARY: There has been an unprecedented explosion in the number of new drugs approved for the treatment of ovarian cancer with three new classes of agent, and five new drugs receiving food and drug administration approval in the last 3 years (Fig. 2). Getting the right drug truly transforms patients' experience with the seminal event being the development of imatinib in CML. In 1980, an average patient would have lived only 3 years, and now they only live 3 years less than a full lifespan [Bower et al. (2016). J Clin Oncol 34:2851].
Subject(s)
Biomedical Research/history , Evidence-Based Medicine , Ovarian Neoplasms/therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/history , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Protocols , Biomedical Research/methods , Biomedical Research/trends , Combined Modality Therapy/adverse effects , Combined Modality Therapy/history , Drug Approval/history , Female , History, 18th Century , History, 19th Century , History, 20th Century , History, 21st Century , Humans , Immunotherapy, Adoptive/adverse effects , Immunotherapy, Adoptive/history , Molecular Targeted Therapy/adverse effects , Molecular Targeted Therapy/history , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/history , Ovarian Neoplasms/mortality , Survival Rate , United States/epidemiology , United States Food and Drug AdministrationABSTRACT
Many people suffering from chronic headaches use headache diaries to help track trends in their episodes. Studies have shown that electronic headache diaries are more effective than paper diaries for both patients and providers. We designed and implemented a full-size and mobile Web-based headache tracker and a database management system to store the data from the websites. The full-size website allows users to retrieve their data by viewing or downloading a table of the raw values they entered, or they can see a graphical visualization linking the severity of their headaches to any of several variables. Through this system's capacity to illustrate trends and track contributing factors for headaches, users, researchers and health service providers may gain better understanding of and control over chronic headaches.
Subject(s)
Computer Graphics , Headache Disorders/classification , Information Storage and Retrieval/methods , Internet , Mobile Applications , Telemedicine/methods , User-Computer Interface , Dictionaries, Medical as Topic , Electronic Health Records , Headache Disorders/diagnosis , Health Records, Personal , HumansABSTRACT
Many people suffering from chronic headaches use headache diaries to help track trends in their episodes. Studies have shown that electronic headache diaries are more effective than paper diaries for both patients and providers. We de-signed and implemented a full-size and mobile Web-based headache tracker and a database management system to store the data from the websites. The fullsize website allows users to retrieve their data by viewing or downloading a table of the raw values they entered, or they can see a graphical visualization linking the severity of their headaches to any of several variables. Through this system's capacity to illustrate trends and track contributing factors for headaches, users, researchers and health service providers may gain better understanding of and control over chronic headaches.
