Metastases to central nervous system (CNS) are very common in nonsmall cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-positive mutation. Brain is the most affected part of CNS where blood-brain barrier (BBB) presents a challenge to currently available chemotherapeutic agents as well as first- (erlotinib and gefitinib) and second (afatinib)-generation EGFR tyrosine kinase inhibitors (TKIs) due to their poor penetrability. A rapid development of EGFR T790M secondary mutation is another cause of treatment failure, and patients tend to progress despite initial response to first- and second-generation EGFR TKIs. Moreover, conventional treatments with heavy dose of radiation have a number of side effects compared to benefits attained. Recently, third-generation EGFR TKIs have been developed with proven efficacy in various clinical setups against EGFR mutation-positive cases of brain metastases in NSCLC. One such agent, osimertinib, is available in India. It has not only better penetration ability to BBB compared to other EGFR TKIs but also has significantly increased potency for most prevalent EGFR T790M mutations. Furthermore, it is active in patients who progress upon first- and second-generation EGFR TKIs. The purpose of this review article is to present an updated clinical preview of EGFR TKIs over conventional treatment, mainly radiation therapy to consider them as "use first" agents against EGFR T790M mutation in the treatment of patients with advanced NSCLC.
Plasma cell leukemia (PCL) is a rare entity. There are two presentations of PCL, primary or secondary. The primary or de novo form of PCL presents with an acute and rapidly progressive leukemic phase. This form occurs when the patient has no pre-existing multiple myeloma (MM). The secondary form is the most advanced form of MM. The PCL is a rare disorder representing 1–2% of the diagnosed cases of MM. Median age at presentation is usually above 50 years. The monoclonal protein in patients with PCL may be IgG (50%), IgA (15%), or in rare cases IgD or IgE (6%). We report a case of IgA primary PCL that is very rare. Patient was started on combination therapy with vincristine, adriamycin, and dexamethasone. There was poor response and patient died three months after diagnosis.
effect on survival.13 of the 30 patients had progressive disease after first-line chemotherapy. DS levels and DS/NT ratio were lower in patients after progression compared with levels at the time of diagnosis (p¼0.013 and 0.033). Conclusion: Lower levels of thiol groups may contribute to lung cancer pathogenesis as a result of enhanced oxidative stress.The deficiency of this antioxidant compounds may relate to structural damage of signal, transcription, apoptosis mechanisms in lung cancer cell lines. The lower levels of DS and DS/NT ratio after progression may be an indicator of the high tumor volume and enhanced cell turnover.Background: Development of brain and leptomeningeal metastases has prognostic and therapeutic implications in oncogene driven non small cell lung cancer (NSCLC). A rising trend is being observed in the incidence of central nervous system (CNS) metastases in such populations, probably due to better imaging techniques as well as improved survival of patients. The presence of EGFR and ALK mutations could have a significant impact on the pattern of metastatic disease spread. Data from the Indian subcontinent on this subject is scarce. The information gained from this study may have clinical relevance in today's era of first line use of second and third generation tyrosine kinase inhibitors (TKIs). Method: 286 EGFR mutated (220) or ALK rearranged (66) NSCLC patients were selected for this retrospective analysis. All patients with clinically suspected CNS metastases underwent contrast enhanced MR imaging of brain. Two groups of patients were identified as per their driver mutation status. The CNS lesions were analysed with regards to number, size, site (parenchymal or meningeal) and nature (morphological heterogeneity and central necrosis) Result: Incidence of brain metastases was found to be higher in the ALK group (24/66, 36.3 %) as compared to the EGFR group (68/220, 30.9%). Leptomeningeal spread in the ALK group was found to be less compared to the EGFR group (2/ 24, 8.3% as opposed to 18/68, 26.4%). Morphological heterogeneity and central necrosis in parenchymal lesions was more common in the ALK group (8/24, 33.3%) as opposed to EGFR group (2/68, 2.94%). Conclusion: The incidence, type and morphology of CNS lesions vary with the driver mutation status in NSCLC patients. This may have prognostic and therapeutic implications, especially in identifying patients who may benefit from upfront second or third generation TKI's.
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