Atezolizumab-induced encephalitis in a patient with metastatic breast cancer: a case report and review of neurological adverse events associated with checkpoint inhibitors

Immune-mediated encephalitis as an adverse event due to checkpoint inhibitors is very rare. We describe herein the case of a 38-year-old woman with metastatic triple-negative breast cancer who developed seizures and somnolence twelve days after receiving the first dose of Atezolizumab. Work up ruled out all infectious etiologies, and the patient was eventually diagnosed with immune-mediated meningoencephalitis. Symptoms recovered with a high-dose of steroids, and she was found to have an excellent response on follow-up imaging, which raised the question of whether a relationship exists between the occurrence, and severity of the adverse event and the response to treatment. Only a few other cases of atezolizumab–related encephalitis have been published. Early recognition and treatment are crucial; the reason why we are describing this case along with a review of the literature and a review on all the neurological immune-related adverse events due to the different checkpoint inhibitors

Evaluation of prophylactic dosages of Enoxaparin in non-surgical elderly patients with renal impairment

BACKGROUND: Thromboprophylaxis dosing strategies using enoxaparin in elderly patients with renal disease are limited, while dose adjustments or monitoring of anti-Xa levels are recommended. We sought to evaluate the efficacy and safety of enoxaparin 20 mg versus 30 mg subcutaneously daily by comparing anti-Xa levels, thrombosis and bleeding. METHODS: We conducted a prospective, single-blinded, single-center randomized clinical trial including non-surgical patients, 70 years of age or older, with renal disease requiring thromboprophylaxis. Patients were randomized to receive either 20 mg or 30 mg of enoxaparin. The primary endpoint was peak anti-Xa levels on day 3. Secondary endpoints included trough anti-Xa levels on day 3, achievement of within range prophylactic target peak anti-Xa levels and the occurrence of hemorrhage, thrombosis, thrombocytopenia or hyperkalemia during hospitalization. RESULTS: Thirty-two patients were recruited and sixteen patients were randomized to each arm. Mean peak anti-Xa level was significantly higher in 30 mg arm (n = 13) compared to the 20 mg arm (n = 11) 0.26 +/- 0.11, 95%CI (0.18-0.34), versus 0.14 +/- 0.09, 95CI (0.08-0.19) UI/ml, respectively; p = 0.004. Mean trough anti-Xa level was higher in 30 mg arm (n = 10) compared to the 20 mg arm (n = 16), 0.06 +/- 0.03, 95CI (0.04-0.08) versus 0.03 +/- 0.03, 95CI (0.01-0.05) UI/ml, respectively; p = 0.044. Bleeding events reported in the 30 mg arm were one retroperitoneal bleed requiring multiple transfusions, and in the 20 mg arm one hematuria. No thrombotic events were reported. CONCLUSION: Peak anti-Xa levels provided by enoxaparin 20 mg were lower than the desired range for thromboprophylaxis in comparison to enoxaparin 30 mg. TRIAL REGISTRATION: The trial was retrospectively registered on ClinicalTrials.gov identifier: NCT03158792 . Registered: May 18, 2017

A patient with metastatic breast cancer 15 years after bilateral prophylactic total mastectomy and oophorectomy

The ideal management of patients carriers of the Breast Cancer gene mutation in clinical practice (BRCA)1 or BRCA2 mutations is unknown. Prophylactic mastectomy and oophorectomy reduces the risk of invasive breast cancer in patients with BRCA1 and BRCA2. The risk of invasive breast cancer is not completely eliminated by prophylactic mastectomy and oophorectomy. We report the case of a patient who underwent prophylactic total mastectomy and oophorectomy and presented with metastatic breast cancer 15 years after the surgeries. To our knowledge this is the first case report of metastatic breast cancer presenting after mastectomy and oophorectomy without evidence of a primary tumor and the first case report of carcinomatous meningitis as a presenting sign of metastatic breast cancer after prophylactic mastectomy and oophorectomy. © 2012 Elsevier Inc

A patient with metastatic breast cancer 15 years after bilateral prophylactic total mastectomy and oophorectomy

The ideal management of patients carriers of the Breast Cancer gene mutation in clinical practice (BRCA)1 or BRCA2 mutations is unknown. Prophylactic mastectomy and oophorectomy reduces the risk of invasive breast cancer in patients with BRCA1 and BRCA2. The risk of invasive breast cancer is not completely eliminated by prophylactic mastectomy and oophorectomy. We report the case of a patient who underwent prophylactic total mastectomy and oophorectomy and presented with metastatic breast cancer 15 years after the surgeries. To our knowledge this is the first case report of metastatic breast cancer presenting after mastectomy and oophorectomy without evidence of a primary tumor and the first case report of carcinomatous meningitis as a presenting sign of metastatic breast cancer after prophylactic mastectomy and oophorectomy. © 2012 Elsevier Inc

Consensus on the management of platinum-sensitive high-grade serous epithelial ovarian cancer in Lebanon

Ovarian cancer is the most lethal gynecologic cancer. The high grade serous epithelial (HGSE) subtype is the most aggressive and it often presents at advanced stages, while screening programs have not proven beneficial. Management of the advanced stages (FIGO III and IV), which constitute the majority of diagnoses, usually consists of platinum-based chemotherapy and cytoreductive surgery (primary or interval) followed by maintenance therapy. Currently, the standard-of-care for advanced newly diagnosed HGSE ovarian cancer, as per international medical societies, starts with upfront cytoreductive surgery, followed by platinum-based chemotherapy (mostly carboplatin and paclitaxel) and/or anti-angiogenic agent bevacizumab, then maintenance therapy with a poly(ADP-ribose) polymerase (PARP) inhibitor with/without/or bevacizumab (continued). PARP inhibitor use depends on the patient’s genetic signature, mainly the breast cancer gene (BRCA) mutation and the homologous recombination deficiency (HRD) status. Therefore, genetic testing is recommended at diagnosis to inform treatment and prognosis.In line with the evolving standard-of-care for ovarian cancer, a panel of experts in treating advanced ovarian cancer convened to lay down practical recommendations on the management of advanced ovarian cancer in Lebanon; since the currently applicable guidelines by the Lebanese Ministry of Public Health for cancer treatment have not been updated yet to reflect the treatment paradigm shift brought upon by the development and approval of PARP inhibitors. The current work reviews the leading clinical trials on PARP inhibitors (as maintenance for newly diagnosed advanced and platinum-sensitive relapsed ovarian cancer), presents international recommendations, and proposes treatment algorithms for optimal local practice

Outcomes of patients with myelodysplatic syndrome and chronic myelomonocytic leukemia post clofarabine failure

BackgroundThe outcome of patients with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) post clofarabine is unknown.MethodsWe reviewed 109 patients with MDS or CMML with a median age of 67 years, treated with a clofarabine-based chemotherapy as frontline (n = 38) or salvage (n = 71) therapy. A total of 58 (53%) patients received salvage therapy after clofarabine failure: 13 allogeneic stem cell transplant (ASCT), 18 high-dose cytarabine-containing regimen, 10 hypomethylating agents and 17 investigational treatments.ResultsEight patients achieved complete remission (CR) and three had stable disease for an overall response rate of 19%. With a median follow-up of 3 months from clofarabine failure, 12 patients (11%) remained alive, 5 remain in CR, 4 of them after ASCT. The median overall survival post clofarabine failure was 4 months with a 1-year survival rate of 23%.ConclusionsThis outcome is predictable, with patients with high-risk disease at the time of clofarabine failure having the worse survival. To date, patients with MDS continue to have a short survival after failure of all available therapies. Ultimately, patients who are candidates for additional treatments should be offered novel approaches. In conclusion, the outcome of patients with MDS and CMML post clofarabine failure is poor. The pattern is similar to patients with MDS post hypomethylating agent failure and predictable using University of Texas M. D. Anderson Cancer Center global scoring system