Erlotinib usage after prior treatment with gefitinib in advanced non-small cell lung cancer: A clinical perspective and review of published literature

Erlotinib and gefitinib are among the most widely researched, used and available molecularly targeted therapies for treatment of advanced non-small cell lung cancer(NSCLC). They are both tyrosine kinase inhibitors(TKIs) of the epidermal growth factor receptor(EGFR). In the past decade, there have been reports on clinical benefit from use of erlotinib after gefitinib failure in NSCLC patients. A review of published literature on this focussed topic is provided herein. Pooled analysis of published literature shows that majority of patients were female(60.6%), non-smokers(64.5%), had adenocarcinoma histology(88.3%) and were of East Asian ethnicity(92.3%). Presence of sensitizing EGFR mutation was detected in 48.4% of subjects. Disease control rates with prior gefitinib therapy and with subsequent erlotinib treatment were 79.4% and 45.4% respectively. Based upon our review, the most important predictive factor for clinical benefit from erlotinib identified was previous response to gefitinib. The exact explanations for the potential benefit from erlotinib use in this patient population is still not known and further studies are required to determine the role of molecular mechanismsespecially those related to resistance to initial EGFR TKI therapy.

Interconversion of two commonly used performance tools: An analysis of 5844 paired assessments in 1501 lung cancer patients

AIM To establish the Karnofsky performance status(KPS) categories which would facilitate the interconversion of the KPS scale to the Eastern Cooperative Oncology Group(ECOG) performance status(PS) scale.METHODS This was a retrospective analysis of all patients attending the lung cancer clinic at a tertiary care center over a 5-year period(September 2009 to August 2014). All patients were assessed with both KPS and ECOG PS scales at each visit. Correlation between KPS and ECOG PS was assessed using Spearman's correlation coefficient. KPS categories equivalent to ECOG PS scores were compared using hit rate and weighted kappa(κw).RESULTS A total of 1501 patients were assessed over the study period, providing 5844 paired KPS and ECOG PS assessments. The study cohort had a mean(standard deviation; SD) age of 58.4(10.8) years, with the majority being current or ex-smokers(76.9%) and males(82.3%). Non-small cell lung cancer was the most common histological type(n = 1196, 79.7%) with the majority having advanced(stage ⅢB/Ⅳ) disease(83.4%). Mean baseline KPS and ECOG PS scores were 77.6(SD = 14.4) and 1.5(SD = 1) respectively. The most frequent KPS score was 80(29%), and the most frequent ECOG PS score was 1(43%). The overall correlation between KPS and ECOG PS was good(Spearman r =-0.84, P < 0.0001) but ranged from-0.727 to-0.972 between visits. KPS categories derived from our cohort [10-40(ECOG 4), 50-60(ECOG 3), 70(ECOG 2), 80-90(ECOG 1), 100(ECOG 0)] performed better [hit rate 78.1%, κw = 0.749(0.736-0.762) P < 0.0001] than those suggested in the past literature.CONCLUSION The current study provides the largest set of paired KPS-ECOG assessments to date. We suggest that the KPS categories 10-40, 50-60, 70, 80-90, and 100 are equivalent to ECOG PS categories of 4, 3, 2, 1, and 0 respectively.

Extrapulmonary small cell carcinoma of lymph node: Pooled analysis of all reported cases

AIM: To study clinical outcomes and management of lymph nodes extrapulmonary small cell carcinoma(LNEPSCC). METHODS: Herein, we perform a systematic search of published literature in the PubMed and EMBASE databases for studies describing LNEPSCC. For uniformity of reporting, LNEPSCC was staged as limited if it involved either single lymph node station or if surgery with curative intent had been undertaken. The disease was staged extensive if it involved two or more lymph node regions.RESULTS: The systematic literature review yielded eight descriptions(n = 14) involving cervical, submandibular and inguinal lymph nodes. Eleven(64.7%) patients had limited disease(LD) and six(35.3%) had extensive disease(ED) at presentation. Chemotherapy(n = 6, 35.3%) or surgery(n = 4, 23.5%) were the most common form of treatment given to these patients. Complete response was achieved in 12(70.6%) of the patients. Median(interquartile range) progression free survival and overall survival was 15(7-42) mo and 22(12.75-42) mo respectively. Of the three illustrative cases, two patients each had ED at presentation and achieved complete remission with platinum based combination chemotherapy.CONCLUSION: LNEPSCC is a rare disease with less than 15 reported cases in world literature. Surgical resection with curative intent is feasible in those with LD while platinum based combination chemoradiation is associated with favorable outcomes in patients with ED. Prognosis of LNEPSCC is better than that of small cell lung cancer in general.

Non-syndromic hypo-hyperdontia—A rare case report and review of literature

Abnormalities of tooth number in development of the dentition are quite common;however, concomitant hypo-hyperdontia is a rare mixed numeric anomalous condition, especially when it occurs in the same dental arch and in a non-syndromic situation. The presence of this condition specifically in the mandibular anterior region is reported very infrequently. This case report presents the case of a 9 years old non-syndromic male with missing mandibular central incisors and an erupted mandibular mesiodens along with the review of literature. To ensure optimum function and aesthetics, cosmetic recontouring was performed after oral prophylaxis. This is the ninth case reported in the dental literature till date, with the two anomalies manifesting in the anterior region of the mandible. This article also discusses the review of literature of concomitant hypo-hyperdontia.

Malignant pleural mesothelioma:The disdained member of thoracic oncology!

Pleural mesothelioma is a very aggressive malignancy that arises from the pleural mesothelial cell lining and is linked strongly to prior asbestos exposure.The ban on asbestos has helped to lower the incidence,but in developing countries like India,it is expected to rise.It has an extended latency period usually progressing over decades and presents with nonspecific symptoms.It has a median survival ranging between 10-22 months.The diagnosis of malignant pleural mesothelioma is challenging and is done using computed tomography(CT),magnetic resonance imaging,or positron emission tomography-CT,with the last two predicting the resectability of the tumor better than CT alone.A pleural biopsy along with an array of immunohistochemical markers,such as p16,BRCA1 associated protein 1,and claudin-4,are required for a definitive diagnosis.Several genetic alterations have prognostic significance as well.The current histological subtype identification is indispensable for decision making because of the new therapeutic avenues being explored.The combination of nivolumab and ipilimumab-based immunotherapy outperformed platinum and pemetrexed-based chemotherapy in terms of survival benefit and improved quality of life especially for non-epithelioid subtypes.However,the latter continues to be a robust treatment option for patients with the epithelioid subtype.Surgery is recommended for resectable cases with radiotherapy being indicated in neoadjuvant,adjuvant,and palliative settings along with systemic treatment.This review article provides an overview of epidemiology,etiology,clinical manifestations,diagnostic approaches(including immunohistochemical and genetic markers),staging,and multidisciplinary approaches to current treatment for malignant pleural mesothelioma using surgery,chemotherapy,immunotherapy,and radiotherapy.It also sheds light on some recent studies(EMPHACIS,CALGB30901,Checkmate-743,etc.)that have led to significant developments in recent years with clinically meaningful results.