Response to trametinib in recurrent low-grade serous ovarian cancer with NRAS mutation: A case report.

Low-grade serous ovarian cancer represents a minority of ovarian cancers and has distinctive features from high grade epithelial ovarian cancer. While less aggressive, in advanced stage they can be poorly chemo-responsive and incur a treatment challenge. Next generation sequencing of tumors has allowed for the potential for targeted therapy in cancer treatment, which can allow for avoidance of traditional cytotoxic chemotherapy. We present a case of a 56 year old female with advanced recurrent low grade serous ovarian cancer found to have NRAS mutation who underwent targeted therapy with trametinib with immediate and sustained disease response. We review the response and toxicity experienced by the patient, as well as treatment for her toxicity.

Adherence to treatment recommendations and outcomes for women with ovarian cancer at first recurrence.

OBJECTIVE: Treatment selection for recurrent ovarian cancer is typically based on the duration of time between the completion of adjuvant, platinum-based therapy and the time of recurrence, the platinum free interval (PFI). We examined the use of, and outcomes associated with platinum-based chemotherapy based on the PFI in women with recurrent ovarian cancer. METHODS: The Surveillance, Epidemiology, and End Results-Medicare database was used to identify women aged >65years with epithelial ovarian cancer who underwent surgery and platinum-based chemotherapy and who developed a recurrence >3months after the completion of adjuvant therapy. Patients were stratified by PFI into 3 groups: PFI <6months, PFI 7-12months, and PFI >12months. Multivariable models were used to examine predictors of use of platinum-based therapy and survival for each group. RESULTS: A total of 2369 patients were identified. In women with a PFI of ≤6months, treatment consisted of platinum-based combination therapy in 28.2%, single agent platinum in 5.2% and non-platinum therapy in 66.6%. Corresponding rates of these treatments among women with a PFI of 7-12months were 39.7%, 12.4% and 47.9%, respectively; the rates were 57.6%, 13.2% and 29.3% in those with a PFI of >12months, respectively. Median survival was 13, 18, and 27months for patients with a PFI of ≤6months, 7-12months, and >12months, respectively (P<0.0001). For all three groups, platinum combination therapy was associated with decreased risk of death compared to non­platinum based therapy. CONCLUSION: Platinum free interval is a strong predictor of survival in elderly women with recurrent ovarian cancer. There is widespread variation in treatment selection for women with recurrent ovarian cancer with many women receiving non-guideline based regimens.

Long-term mortality among women with epithelial ovarian cancer.

OBJECTIVES: Patients with solid tumors are at greatest risk for dying from their cancers in the five years following diagnosis. For most malignancies, deaths from other chronic diseases begin to exceed those from cancer at some point. As little is known about the causes of death among long-term survivors of ovarian cancer, we examined causes of death by years from diagnosis. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women diagnosed with ovarian cancer between 1988 and 2012. We compared causes of death by stage, age, and interval time after diagnosis. RESULTS: A total of 67,385 women were identified. For stage I neoplasms, 13.6% (CI, 13.0-14.2%) died from ovarian cancer, 4.2% (CI, 3.8-4.5%) from cardiovascular disease, 3.6% (CI, 3.3-3.9%) from other causes and 2.6% (CI, 2.4-2.9%) from other tumors; ovarian cancer was the leading cause of death until 7 years after diagnosis after which time deaths are more frequently due to other causes. For those with stage III-IV tumors, 67.8% (CI, 67.3-68.2%) died from ovarian cancer, 2.8% (CI, 2.6-2.9%) from other causes, 2.3% (CI, 2.2-2.4%) from cardiovascular disease and 1.9% (CI, 1.7-2.0%) from other cancers; ovarian cancer was the most frequent cause of death in years 1-15 after which time deaths were more commonly due to other causes. CONCLUSIONS: The probability of dying from ovarian cancer decreases with time. Ovarian cancer remains the most common cause of death for 15 years after diagnosis in women with stage III-IV tumors.

Protein targets for broad-spectrum mycosis vaccines: quantitative proteomic analysis of Aspergillus and Coccidioides and comparisons with other fungal pathogens.

Aspergillus species are responsible for most cases of fatal mold infections in immunocompromised patients, particularly in those receiving hematopoietic stem cell transplants. Experimental vaccines in mouse models have demonstrated a promising avenue of approach for the prevention of aspergillosis, as well as infections caused by other fungal pathogens, such as Coccidioides, the etiological agent of valley fever (coccidioidomycosis). Here, we investigated the hyphal proteomes of Aspergillus fumigatus and Coccidioides posadasii via quantitative MS(E) mass spectrometry with the objective of developing a vaccine that cross-protects against these and other species of fungi. Several homologous proteins with highly conserved sequences were identified and quantified in A. fumigatus and C. posadasii. Many abundant proteins from the cell wall of A. fumigatus present themselves as possible cross-protective vaccine candidates, due to the high degree of sequence homology to other medically relevant fungal proteins and low homologies to human or murine proteins.