Roland Eid

New developments in the management of head and neck cancer – impact of pembrolizumab

Head and neck squamous cell carcinoma (HNSCC), a heterogeneous group of upper aerodigestive tract malignancies, is the seventh most common cancer worldwide. Tobacco use and alcohol consumption were the most identified risk factors of HNSCC. However, human papilloma virus, a sexually transmitted infection, has been determined as another primary cause of HNSCC. Early-stage disease is treated with surgery or radiotherapy. Recurrent or metastatic HNSCC is associated with poor prognosis with a median overall survival of 10 months. The EXTREME protocol is commonly used in first-line setting. Recently, pembrolizumab, an anti-programmed death-1 agent, has been approved by the US Food and Drug Administration for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy. It demonstrated a durable objective response rate with a good safety profile and quality of life. Many ongoing trials are evaluating the use of pembrolizumab for the treatment of HNSCC in various indications such as adjuvant and neoadjuvant setting, maintenance and recurrent disease, alone or in combination with chemotherapy, radiation and targeted therapy. Finding those biomarkers predictive of response to immune checkpoints inhibitors has been a major concern. However, markers have been identified, such as PD-L1 expression, human papilloma virus infection, interferon-γ signature score, microsatellite instability and neoantigen production.

Watch and Wait in Lebanese Chronic Lymphocytic Leukemia Patients: How Relevant is it?

BACKGROUND Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in Europe and North America, and it mainly affects older individuals. Many approaches are implemented in the management of CLL from a watch and wait (WandW) strategy to chemotherapeutic regimens. We here reviewed our clinical practice for the relevance of the W and W strategy in Lebanese CLL patients. MATERIALS AND METHODS A total of 95 patients with CLL diagnosed in four institutions in Lebanon, between 1992 and 2013, were selected and their files were reviewed. Characteristics of these patients were noted including age, sex, RAI and Binet scores, CBC values, presence of hepatomegaly or splenomegaly, performance of bone marrow biopsy or peripheral blood flux cytometry for diagnosis, adoption of W and W strategy, different chemotherapeutic regimens and the indications for treatment. RESULTS Some 38 patients (40%) diagnosed with CLL were women and 57 (60%) were men with a mean age of 65.1 years [36-89]. Of the total, 50.5%, 17.2%, 14%, 7.5% and 10.8% had an RAI score at diagnosis of 0, 1, 2, 3 and 4, respectively, while 65.6%, 17.2% and 17.2% had Binet scores of I, II and III. The mean lymphocyte count at diagnosis was 39885/mm3 [1596-290000], the mean hemoglobin level was 12.7 g/dl [6.2-17] and the mean platelet count was 191255/mm3 [14000-458000]. While 26.3% of patients with CLL had splenomegaly, only 7.4% had hepatomegaly. Some 33.7% had undergone a bone marrow biopsy, 66.3% flow cytometry of circulating blood and 5.3% a lymph node biopsy. Overall, the W and W was adopted in 62.4% (58) of patients with a mean duration of 37.7 months [3-216]. The W and W was used in 82.6%, 73.3%, 46.2%, 14.3% and 0% of patients having RAI scores of 0, 1, 2, 3 and 4, respectively, and, it was used in 80%, 46.7% and 6.25% with Binet scores of I, II and III. The most frequent indication for treatment was anemia and thrombocytopenia, accounting for 32.7% of cases. The most frequently used chemotherapeutical regimens were chlorambucil until the end of the last century and flufarabine-cyclophosphamide-rituximab during the last decade. CONCLUSIONS This retrospective review of CLL clinical practice showed an important implementation of the W and W strategy with a long duration, especially in early stage cases with low RAI or Binet scores.

ALK-rearranged adenocarcinoma transformed to small-cell lung cancer: a new entity with specific prognosis and treatment?

Driving molecular mutations such as rearrangement of ALK and EGFR mutation is present in 5-10% of non-small-cell lung cancer. Tyrosine kinase inhibitors have shown good efficacy and thus become the standard of care. However, tumors have developed several resistance mechanisms against tyrosine kinase inhibitors, including transformation to small-cell lung carcinoma (SCLC). Transformation to SCLC after administration of anti-EGFR in EGFR-mutated adenocarcinoma has been well documented. Similarly, it appears that the same transformation happens in ALK-rearranged adenocarcinoma after the use of anti-ALK. In fact, to date eight cases have been reported in the literature. We aimed in this paper to focus on the characteristics, prognosis and treatment of these transformed SCLC.

Aggressive Grade 2 Neuroendocrine Tumor Salvaged by Temozolomide- Based Therapy: A Case Report and Literature Review

We are reporting a 59-year-old woman with a grade 2 (G2) moderately differentiated metastatic neuroendocrine (NET) tumor of unknown origin with Ki67 rate of 15%. First-line treatment with etoposide and cisplatin failed with evidence of rapid disease progression. However, second-line therapy with temozolomide associated to capecitabine proved an unexpected efficacy resulting in a consistent partial response. Immunohistochemistry staining for O-6methylguanine-DNA methyltransferase (MGMT) expression was performed retrospectively and was negative, which could predict response to temozolomide. Systematic treatment strategies of non-well differentiated NETs are reviewed, as well as the role of MGMT as predictive factor for the efficacy of temozolomide. differentiated (G2) neuroendocrine tumor was confirmed. Gallium scan showed the same pattern of disease extension but failed to identify a primary lesion. Chromogranin serum assessment was not done. 24hour urine 5-hydroxyindoleacetic acid was within normal range. The patient received cytotoxic chemotherapy with etoposide 100 mg/m2 intravenously (IV) on days 1 to 3 and cisplatin 75 mg/m2 day 1 of a 21 day cycle for four cycles, associated with zoledronic acid 4 mg IV. Pain and weight loss increased after the second cycle, along with progression of the lesions by more than 75% on subsequent disease assessment. She received second-line therapy with temozolomide 150 mg/m2 divided into two doses daily on days 1 to 5, and capecitabine 600 mg/m2 orally twice daily on days 1-14 of a 21-day cycle. After the completion of her second cycle, the patient presented with a complete disappearance of her pain, regain of appetite and weight, as well as a decrease in disease extension of more than 30%. Actually, the disease remains in sustained partial response while the patient is receiving the eighth cycle. MGMT IHC was subsequently performed (Caris Life Sciences) and was negative (2% staining).