Molecularly targeted therapies in non-small cell lung cancer: The evolving role of tyrosine kinase inhibitors.

Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer. Patients with NSCLC are diagnosed at a locally advanced or metastatic stage where prognosis with palliative chemotherapy is poor. The discovery of epidermal growth factor receptor (EGFR) mutations has revolutionized cancer treatment for NSCLC by promoting the development of molecularly targeted therapies like tyrosine kinase inhibitors (TKIs). This review summarizes the clinical efficacy and tolerability of EGFR-TKIs, including osimertinib, in EGFR-mutated advanced NSCLC. EGFR-TKIs have demonstrated superior response and overall survival rates compared with chemotherapy in EGFR-mutated NSCLC. However, despite the initial rapid and durable clinical responses, acquired resistance to first- and second-generation TKIs eventually develops in most cases, with disease progression observed mostly within 12 months of treatment initiation. Osimertinib, a potent third-generation TKI, irreversibly inhibits mutated EGFR alleles, including T790M. In addition to longer survival and higher response rate, osimertinib has a favorable safety profile with a lower incidence of grade ≥3 treatment-related adverse events compared with other TKIs. Based on the efficacy and safety results, recently the National Comprehensive Cancer Network (NCCN) has included osimertinib as the "preferred first-line of treatment" in patients with metastatic EGFR mutationpositive NSCLC. Thus, osimertinib as first-line therapy for EGFRpositive patients irrespective of the T790M mutation status could be an ideal choice in the Indian setting where only 50% of patients opt for any second-line therapy after first-line failure.

Biomarkers in Non-Small Cell Lung Cancers: Indian Consensus Guidelines for Molecular Testing.

Novel molecular targets and promising targeted therapies have reshaped diagnostics in patients with advanced non-small cell lung cancer (NSCLC). Despite this progress, the implementation of molecular screening to identify predictive biomarkers in Indian clinical and pathology settings has been challenging due to operational and logistical constraints. This consensus guideline brings together medical oncologists, molecular pathologists and pathologists from India to provide a quick and competent reference for biomarker testing in NSCLC. The guideline summarizes the importance of targetable mutations in NSCLC such as epidermal growth factor receptor (EGFR), rearrangements in anaplastic lymphoma kinase and receptor tyrosine kinase encoded by ROS-1 gene, overexpression of programmed cell death ligand-1 and resistant EGFR mutations. It reaffirms recommendations from international working groups, discusses vulnerable pre-analytical procedures and provides a balanced review on the pros and cons of different diagnostic tests (immunohistochemistry, fluorescence in situ hybridization, polymerase chain reaction-based testing and next-generation sequencing). The document also provides an algorithm to aid diagnostic decision-making and a checklist to assess the quality of testing laboratories that will help the medical oncologists make an informed choice. Overall, these recommendations are based on evidence and clinical experience and will aid policymakers, oncologists, health care practitioners and pathologists who strive to implement molecular strategies and make informed decisions for improved care in NSCLC in India.Funding: AstraZeneca Pharma India Limited.

Practical consensus recommendations on ovarian suppression in early breast cancer (adjuvant).

Substantial survival benefits exist for patients with early-stage breast cancer who undergo treatment with single-modality ovarian suppression, but its value is uncertain. Expert oncologist discussed to determine whether additional benefits exist with ovarian suppression plus multiple adjuvant therapy which provides a new treatment option that reduces the risk of recurrence in early breast cancer. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

Advanced therapeutic options and importance of rebiopsy in epidermal growth factor receptor-tyrosine kinase inhibitor-progressed nonsmall cell lung carcinoma patients: An expert opinion.

Advanced nonsmall cell lung cancer (NSCLC) treatment is primarily based on platinum-based chemotherapy. Although epidermal growth factor receptor (EGFR) targeting has shifted the treatment paradigm toward personalized tyrosine kinase inhibitors (TKIs), resistance develops inevitably and EGFR T790M is the most common acquired resistance mechanism. Rebiopsy of resistant NSCLC cases can provide additional information on the underlying resistant mechanisms and therefore can help clinicians in taking better management decisions. An expert panel meeting of renowned cancer oncologists was held to discuss the management of advanced-stage NSCLC. The present paper is based on the recommendations made by the expert panel and is supported by an exhaustive literature search. It was suggested that identification of driver mutation leads to better treatment decisions. TKIs have proven to be better treatment option in EGFR-positive patients as compared to chemotherapy. Third-generation TKIs (osimertinib) promise to bring optimal and improved care for NSCLC cases failing first-line TKI treatment.

Unusual metastasis in colorectal cancer.

Metastasis from colorectal carcinoma occurs by either lymphatic or hematogenous spread. The most common sites of colorectal metastasis are the liver and lung. Involvement of the skin, muscles and bones are quite rare. The prognosis in such patients is usually poor. Herewith, we are reporting a case of colonic carcinoma who had cutaneous metastasis, muscular involvement and diffuse skeletal metastasis. At the end, she had brain metastasis, but liver and lung involvement was not observed till the end.

Simultaneous occurrence of multiple myeloma and acute myeloid leukemia.

Multiple myeloma and acute leukemia may sometimes occur in the same patient, usually in patients with myeloma who receive chemotherapy and subsequently develop acute leukemia. However, simultaneous occurrence of myeloma and acute leukemia on presentation is rare, with only a handful of such cases reported in the literature.

Waldenstrom's macroglobulinemia.

Waldenstrom's macroglobulinemia is an uncommon lymphoplasmacytic lymphoma presenting with hyperviscocity and autoimmune phenomenon. Disease is characterized by bone marrow infiltration by lymphoplasmacytic cells and raised IgM. Bone marrow morphology and immunohistochemistry is important for diagnosis. Course is indolent and anemia and age are most important prognostic factors. Treatment options include alkylating agents, anti-purine anti-metabolites, which though not curative but offer valuable responses. Newer agents like Rituximab and autologous transplant are being tried.

ICON 2013: practical consensus recommendations for hormone receptor-positive Her2-negative advanced or metastatic breastcancer.

The management of hormone receptor-positive Her2-negative breast cancer patients with advanced or metastatic disease is a common problem in India and other countries in this region. This expert group used data from published literature, practical experience, and opinion of a large group of academic oncologists, to arrive at practical consensus recommendations for use by the community oncologists.

Sino-oral zygomycosis due to Absidia corymbifera in a patient with acute leukemia.

Fungi belonging to class Zygomycetes become pathogenic in certain predisposing conditions; principally diabetes mellitus, immunosuppression, trauma or burns. We report a case of a 31-year-old man with acute promyelocytic leukemia who developed infection of the sino-oral cavity, due to Absidia corymbifera during a neutropenic phase following induction chemotherapy. A provisional diagnosis of zygomycosis was made by demonstration of broad aseptate branching filamentous hyphae in the scrapings of the palate, which was subsequently confirmed as A. corymbifera by culture. Surgical debridement could not be done due to the thrombocytopenic status of the patient; instead antifungal therapy with amphotericin B was instituted. However, the patient succumbed to the infection after 15 days of its diagnosis. Although infections with Absidia are infrequent, this case highlights the need for its awareness as a potentially lethal opportunistic fungal infection that can present even with short duration of exposure to the usual risk factors.