The Cancer Journal最新文献

{"title":"Real-World Evidence for Chronic Lymphocytic Leukemia in the Era of Targeted Therapies","authors":"P. Islam, A. Mato","doi":"10.1097/PPO.0000000000000407","DOIUrl":"https://doi.org/10.1097/PPO.0000000000000407","url":null,"abstract":"Abstract The landscape of chronic lymphocytic leukemia has transformed in the era of small molecule inhibitor targeted therapies. While randomized controlled trials remain the criterion standard in evaluating new therapies, they are often unable to keep pace with the clinical questions that arise during the use of novel agents. Real-world evidence is generated through analysis of data such as electronic medical records, payer claims, and patient registry databases and can provide invaluable information to supplement randomized controlled trials, such as outcomes in patient populations excluded from clinical trials, rates of discontinuation or dose reductions in clinical practice, survival outcomes, and optimal sequencing of novel agents. This review aims to discuss major findings from recent, relevant, real-world evidence publications that have greatly informed our understanding of chronic lymphocytic leukemia as it is treated in clinical practice.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"4 1","pages":"442 - 448"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81841803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Shifting Paradigm in Chronic Lymphocytic Leukemia","authors":"N. Jain, S. O'brien","doi":"10.1097/PPO.0000000000000417","DOIUrl":"https://doi.org/10.1097/PPO.0000000000000417","url":null,"abstract":"Abstract Chemoimmunotherapy (CIT) was the standard treatment for patients with chronic lymphocytic leukemia for the last 2 decades. Recently, with the introduction of targeted therapies, the role of CIT has declined significantly. In the first-line setting, the role of CIT is limited to young fit patients with mutated immunoglobulin heavy chain variable region and without del(17p)/TP53 mutation. There is a limited role for CIT in relapsed chronic lymphocytic leukemia.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"9 1","pages":"374 - 377"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78765609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Therapy in Chronic Lymphocytic Leukemia","authors":"T. Kipps, M. Choi","doi":"10.1097/PPO.0000000000000416","DOIUrl":"https://doi.org/10.1097/PPO.0000000000000416","url":null,"abstract":"Abstract Despite a prevailing view that advances in cancer therapy will come through selective targeting of enzymes encoded by mutated oncogenes responsible for the neoplastic phenotype, recent advances in the treatment of patients with chronic lymphocytic leukemia (CLL) have instead exploited knowledge of its biology. Indeed, CLL cells depend on interactions with cells and soluble factors present in the tumor microenvironment for proliferation and survival. B-cell receptor signaling and chemokine-receptor signaling play prominent roles. Elucidation of these signaling pathways has defined physiologic targets for drugs, such as ibrutinib, which inhibit Bruton tyrosine kinase and are therapeutically effective. The characteristic high-level expression of BCL2 in CLL that can enhance leukemia-cell survival has now become an Achilles heel targeted by clinically effective drugs such as venetoclax. Here we discuss advances in such targeted therapy and highlight other disease attributes, such as the distinctive expression of ROR1, which may be targeted for clinical benefit, alone or in combination with other targeted therapies.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"298 1","pages":"378 - 385"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76475824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resistance Mechanisms to Targeted Agents in Chronic Lymphocytic Leukemia","authors":"A. Kittai, J. Woyach","doi":"10.1097/PPO.0000000000000406","DOIUrl":"https://doi.org/10.1097/PPO.0000000000000406","url":null,"abstract":"Abstract Agents that specifically target pathologic mechanisms of survival have now been approved for the treatment of chronic lymphocytic leukemia in both the treatment-naive and relapsed/refractory settings. These 4 agents include the Bruton tyrosine kinase inhibitor ibrutinib, the B-cell leukemia/lymphoma-2 inhibitor venetoclax, and the phosphatidylinositol-3 kinase inhibitors idelalisib and duvelisib. Although clinical outcomes are improved with all of these inhibitors, acquired resistance does occur and leads to progression of disease. Resistance to targeted therapy can occur through direct mutations of the target or through the overexpression of alternative cell survival pathways not affected by the specific inhibitor. Determining which patients will develop resistance, why resistance occurs, how to overcome resistance, and when to test for resistance are all subjects of ongoing research. In this review, we describe the current data relative to the development of resistance to targeted therapies in CLL.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"1 1","pages":"428 - 435"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85232020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relevance of Minimal Residual Disease in the Era of Targeted Agents","authors":"S. Heltai, P. Ghia, L. Scarfò","doi":"10.1097/PPO.0000000000000413","DOIUrl":"https://doi.org/10.1097/PPO.0000000000000413","url":null,"abstract":"Abstract The evaluation of minimal residual disease (MRD) in chronic lymphocytic leukemia (CLL) has evolved in parallel with the enormous progresses in the therapeutic armamentarium and the application of cutting-edge diagnostic techniques the CLL community witnessed in the past few years. Minimal residual disease is considered an objective measure of disease status defined by the number of residual leukemic cells detected in a sample of peripheral blood and/or bone marrow as proportion of the total white blood cells and defined undetectable if fewer than 1 CLL cell among 10,000 white blood cells (10−4 or 0.01%) is detected. In this review, we aim at shedding light on how to evaluate MRD, what we already know about MRD from the experience with chemoimmunotherapy, and why MRD evaluation remains still relevant in the era of targeted agents.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"58 1","pages":"410 - 417"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84770432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visit-to-Visit Hemoglobin A1c Variability Is Associated With Later Cancer Development in Patients With Diabetes Mellitus","authors":"Yuki Saito, H. Noto, O. Takahashi, D. Kobayashi","doi":"10.1097/PPO.0000000000000387","DOIUrl":"https://doi.org/10.1097/PPO.0000000000000387","url":null,"abstract":"Purpose Recent studies have shown that patients with diabetes mellitus have a higher risk of tumorigenesis. However, the effect of glycemic variability on tumorigenesis among diabetic patients has not been well investigated. Hence, we performed a retrospective cohort study to analyze the effect of visit-to-visit hemoglobin A1c (HbA1c) variability and later onset of malignancies. Methods This study included 2640 patients with diabetes mellitus 50 years or older. To analyze visit-to-visit glycemic activity, we calculated intrapersonal SD of all recorded HbA1c and used SD-HbA1c as a measure of glycemic variability. Because the number of individual visits varied, we divided SD-HbA1c by visit times in order to adjust for the potential influence of visit time difference between individuals. Patients were divided into quartiles according to their HbA1c variability, and Cox regression models were used to evaluate the association between glycemic variability and later onset of tumorigenesis. Results Three hundred thirty patients (12.5%) developed malignancy during follow-up. The median follow-up period was 1511 days (4.1 years; interquartile range, 2487.5 days). Relative to the group with the lowest glycemic variability (first quartile), the groups with higher glycemic variability showed a dose-dependent association with tumorigenesis. The odds ratios for the second, third, and fourth quartiles were 1.20 (95% confidence interval, 0.88–1.65), 1.43 (1.02–2.00), and 2.19 (1.52–3.17), respectively. The mean HbA1c and diabetes mellitus duration periods were not significantly associated with tumorigenesis. This result was consistent when limiting the number of covariates. Conclusions These results demonstrated that visit-to-visit HbA1c variability is a potential risk factor for later tumorigenesis. The association may be mediated by oxidative stress or hormone variability. Routine cancer screening may be suggested for diabetic patients with unstable glycemic control.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"20 1","pages":"237 - 240"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90858168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision Cancer Trials With Immunomodulatory Agents","authors":"M. Baretti, N. Azad","doi":"10.1097/PPO.0000000000000390","DOIUrl":"https://doi.org/10.1097/PPO.0000000000000390","url":null,"abstract":"Abstract Advances in high-throughput technologies have yielded impressive insights into the molecular biology behind cancers, resulting in a powerful ally for the development of biomarkers-selected clinical trials, which are critical for translating our genomic knowledge into clinically meaningful outcomes. “Basket studies” or histology-agnostic clinical trials in biomarker-defined populations represent an important research strategy to continue making progress in this field. The recent accelerated US Food and Drug Administration approvals of anti–programmed death 1 pembrolizumab and nivolumab for mismatch repair–deficient cancers, as well as larotrectinib for cancers carrying TRK fusions, support the fundamental premise that some cancers may be best classified based on molecular phenotype and not site of origin. The studies that were conducted showing the efficacy of this approach serve as validation of the basket study paradigm. In the field of immune oncology, the advent of tumor agnostic strategies represents an important step toward discovering biomarkers of response and elucidating mechanisms of treatment efficacy and resistance across a variety of cancer types. We present a review and discussion of the progress in biomarker-defined approaches to drug development in immunology.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"14 1","pages":"287 - 295"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73130875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycemic Variation and Cancer Occurrence—A New Paradigm","authors":"Rajeev Sharma","doi":"10.1097/PPO.0000000000000388","DOIUrl":"https://doi.org/10.1097/PPO.0000000000000388","url":null,"abstract":"","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"25 1","pages":"241 - 242"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75142511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining, Identifying, and Understanding “Exceptional Responders” in Oncology Using the Tools of Precision Medicine","authors":"A. Tsimberidou, R. Said, L. Staudt, B. Conley, N. Takebe","doi":"10.1097/PPO.0000000000000392","DOIUrl":"https://doi.org/10.1097/PPO.0000000000000392","url":null,"abstract":"Abstract Widely available molecular profiling technology, including next-generation sequencing has changed the landscape of drug development in cancer. An increasing number of clinical trials in early drug development require patient selection based on molecular alterations. Concurrently, efforts to identify molecular alterations in tumors that exhibited exceptional response after systemic treatment with standard or investigational agents have been published or are in progress. These discoveries may ultimately serve as predictive markers or “actionable mutations” for future therapies. To test the feasibility of collecting the archival tissues from proposed exceptional responder patients and successful subsequent molecular profiling, the National Cancer Institute opened a nationwide exceptional responder initiative protocol in 2014. In addition, an increasing number of exceptional responder cases have been identified and published from academia institutions. The Network of Enigmatic Exceptional Responders study uses crowdsourcing to identify exceptional responders and will molecularly profile tumors to discern molecular correlates with exceptional response. In this review, we discuss the potential role of exceptional responder molecular analysis in new biomarker discovery efforts to further advance precision medicine in oncology therapeutics.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"32 1","pages":"296 - 299"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77829897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Errors in Genetic Testing: The Fourth Case Series","authors":"Meagan B. Farmer, Danielle C. Bonadies, S. Mahon, M. Baker, Sumedha Ghate, Christine Munro, Chinmayee B. Nagaraj, A. Besser, Kara Bui, Christen M Csuy, B. Kirkpatrick, A. McCarty, S. McQuaid, Jessica Sebastian, D. Sternen, L. Walsh, E. Matloff","doi":"10.1097/PPO.0000000000000391","DOIUrl":"https://doi.org/10.1097/PPO.0000000000000391","url":null,"abstract":"Purpose In this ongoing national case series, we document 25 new genetic testing cases in which tests were recommended, ordered, interpreted, or used incorrectly. Methods An invitation to submit cases of adverse events in genetic testing was issued to the general National Society of Genetic Counselors Listserv, the National Society of Genetic Counselors Cancer Special Interest Group members, private genetic counselor laboratory groups, and via social media platforms (i.e., Facebook, Twitter, LinkedIn). Examples highlighted in the invitation included errors in ordering, counseling, and/or interpretation of genetic testing and did not limit submissions to cases involving genetic testing for hereditary cancer predisposition. Clinical documentation, including pedigree, was requested. Twenty-six cases were accepted, and a thematic analysis was performed. Submitters were asked to approve the representation of their cases before manuscript submission. Results All submitted cases took place in the United States and were from cancer, pediatric, preconception, and general adult settings and involved both medical-grade and direct-to-consumer genetic testing with raw data analysis. In 8 cases, providers ordered the wrong genetic test. In 2 cases, multiple errors were made when genetic testing was ordered. In 3 cases, patients received incorrect information from providers because genetic test results were misinterpreted or because of limitations in the provider's knowledge of genetics. In 3 cases, pathogenic genetic variants identified were incorrectly assumed to completely explain the suspicious family histories of cancer. In 2 cases, patients received inadequate or no information with respect to genetic test results. In 2 cases, result interpretation/documentation by the testing laboratories was erroneous. In 2 cases, genetic counselors reinterpreted the results of people who had undergone direct-to-consumer genetic testing and/or clarifying medical-grade testing was ordered. Discussion As genetic testing continues to become more common and complex, it is clear that we must ensure that appropriate testing is ordered and that results are interpreted and used correctly. Access to certified genetic counselors continues to be an issue for some because of workforce limitations. Potential solutions involve action on multiple fronts: new genetic counseling delivery models, expanding the genetic counseling workforce, improving genetics and genomics education of nongenetics health care professionals, addressing health care policy barriers, and more. Genetic counselors have also positioned themselves in new roles to help patients and consumers as well as health care providers, systems, and payers adapt to new genetic testing technologies and models. The work to be done is significant, but so are the consequences of errors in genetic testing.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"36 1","pages":"231 - 236"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91304235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}