A case of indolent systemic mastocytosis responding to treatment with Avapritinib.

Low dose Avapritinib is a new medication that is a potential treatment option not just for advanced systemic mastocytosis, but also for the indolent form.

Circulating tumor DNA use in a community oncology practice.

BACKGROUND: This retrospective single center study aimed to describe circulating tumor DNA (ctDNA) comprehensive genomic profiling (CGP) utilization in a community practice for patients with advanced solid tumors. METHODS: All patients were included who were seen at the Scripps Hillcrest Oncology Clinic (San Diego, CA, USA) between September 2016 to March 2018 who had ctDNA assay testing performed. In this cohort, all ctDNA testing was performed to aid therapeutic decision making with wide variety in both the type of advanced solid tumor, as well as the line of therapy. RESULTS: Of the assays performed in the 41 patients included in this review, 42% of therapeutic actions following ctDNA assay results were influenced by the ctDNA result, including initiation of the corresponding Federal Drug Administration (FDA) approved therapy, placement on clinical trial, and initiation of off label-targeted options. In addition, CGP results guided clinicians away from futile or harmful treatments, such as EGFR inhibition in colorectal cancer patients with discovered KRAS mutations. No additional prognostic or therapeutic information was gathered in one quarter of patients for which ctDNA was drawn. Furthermore, discovered genomic alterations by ctDNA testing did not influence therapeutic action in 58% of cases. CONCLUSIONS: These results highlight the conundrum that having additional information regarding an individual's tumor biology does not yet translate into meaningful targeted therapy in the majority of cases. Further studies are needed regarding ctDNA utilization to help guide community oncologists who will continue to face the choice between targeted therapy, immunotherapy, and cytotoxic chemotherapy as science advances.

Activity of Entrectinib in a Patient With the First Reported NTRK Fusion in Neuroendocrine Cancer.

Despite advances in genomic analysis, the molecular origin of neuroendocrine tumors (NETs) is complex and poorly explained by described oncogenes. The neurotrophic TRK family, including NTRK1, 2, and 3, encode the proteins TRKA, TRKB, TRKC, respectively, involved in normal nerve development. Because NETs develop from the diffuse neuroendocrine system, we sought to determine whether NTRK alterations occur in NETs and whether TRK-targeted therapy would be effective. A patient with metastatic well-differentiated NET, likely of the small intestine, was enrolled on the STARTRK2 trial (ClinicalTrials.gov identifier: NCT02568267) and tissue samples were analyzed using an RNA-Seq next-generation sequencing platform. An ETV6:NTRK3 fusion was identified and therapy was initiated with the investigational agent entrectinib, a potent oral tyrosine kinase inhibitor of TRKA, TRKB, and TRKC. Upon treatment with entrectinib, the patient experienced rapid clinical improvement; his tumor response was characterized by initial tumor growth and necrosis. This is the first report of an NTRK fusion in NETs. Our patient's response to entrectinib suggests that NTRK fusions can be important in the pathogenesis of NETs. Recent DNA-based genomic analyses of NETs may have missed NTRK fusions due its large gene rearrangement size and multiple fusion partners. The tumor's initial pseudoprogression may represent a unique response pattern for TRK-targeted therapies. An effort to characterize the prevalence of NTRK fusions in NETs using optimal sequencing technology is important.

Antioxidants in the Treatment of Cancer.

Several clinical trials have produced conflicting results regarding the benefit of antioxidants in cancer therapy thus questioning the incorporation of these substances in standard treatment regimens. Vitamins E and C, selenium, carotenoids, lycopene, soy products, and green tea extract are a few substances with antioxidant properties that have been studied in detail. This article reviews the results generated over the last 20 years through in vitro and in vivo studies in various types of cancers and stages of cancer treatment. Despite the commercial popularity and the multitude of studies examining antioxidant therapy, the true role of antioxidants is yet to be determined, requiring further investigation into its propagative, causal, or protective nature.

Melanoma in patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma.

BACKGROUND: The relationship between melanoma and chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL) has been minimally investigated. OBJECTIVE: The objective of this study was to examine the incidence of melanoma in patients with a history of CLL or NHL, and their associated mortality. METHODS: Cohorts of Kaiser Permanente Southern California members with a history of CLL and NHL were identified. Age-adjusted incidence density rates of melanoma among patients with CLL or NHL were compared with rates of melanoma among the general population of Kaiser Permanente Southern California patients. The mortality of patients with melanoma was examined using Cox proportional hazards modeling. RESULTS: The age-adjusted incidence rate per 100,000 person-years for melanoma among patients with either CLL or NHL was 107 (95% confidence interval 84.4-129.6) versus 25.9 among the general population (95% confidence interval 84.4-129.6, P < .001). Patients with melanoma and a history of CLL or NHL had 2.46 greater odds of death compared with those without CLL or NHL (95% confidence interval 1.77-3.41). LIMITATIONS: This study was retrospective in nature; the International Classification of Diseases, Ninth Revision codes used may contain diagnostic errors; and only overall survival was used in our analysis. CONCLUSIONS: Patients with a history of CLL or NHL have a higher incidence of melanoma. Patients with CLL or NHL who are subsequently given the diagnosis of melanoma have a higher mortality than patients with melanoma without a preceding diagnosis of CLL.

Bilateral nephrectomy for the treatment of refractory lupus nephritis with features overlapping with thrombotic microangiopathy resembling thrombotic thrombocytopenia purpura.

We report a patient with a diagnosis of systemic lupus erythematosus who concurrently developed a syndrome of thrombotic microangiopathy that resembled thrombotic thrombocytopenic purpura. The patient underwent plasma exchange and immunosuppressive therapy for months before clinical improvement was finally achieved through bilateral nephrectomy. Ultimately, our patient died of disseminated aspergillosis from prolonged immunosuppression. We believe that recognition of bilateral nephrectomy as a potential treatment earlier in her course would have spared her this unfortunate demise. We hope that this review of current literature will help the reader to consider bilateral nephrectomy in patients with refractory systemic lupus erythematosus with clinical overlap of thrombotic microangiopathy resembling thrombotic thrombocytopenic purpura.