G. Kasymjanova

Epidermal Growth Factor Receptor Mutations Detected by Denaturing High-Performance Liquid Chromatography in Nonsmall Cell Lung Cancer Impact on Response to Therapy With Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors

Somatic mutations in the epidermal growth factor receptor (EGFR) kinase domain are associated with sensitivity to EGFR‐tyrosine kinase inhibitors (EGFR‐TKI) in patients with nonsmall cell lung cancer (NSCLC).

Lung cancer histologies associated with emphysema on computed tomography

BACKGROUNDnMultiple studies have demonstrated an increased risk of lung cancer in the presence of emphysema detected visually on computed tomography (CT) independent of smoking history and airflow obstruction. The relationship between emphysema and specific histologic subtypes of lung cancer remains uncertain.nnnOBJECTIVEnTo determine the extent to which emphysema on chest CT is associated with lung cancer histology.nnnMETHODSnCross-sectional analysis of consecutive lung cancer patients referred to the Jewish General Hospital was performed (2001-2009). All those with demographic data, smoking history (pack-years), documented histology and chest CT were included. Emphysema was graded on CT by three readers, using a standardized rubric. Odds of each lung cancer subtype were compared between patients with and without emphysema, and adjusted for age, sex, physician diagnosed COPD and smoking history by multiple logistic regression.nnnRESULTSnComplete data were available for 498 lung cancer patients (mean age 68 years; 44% female; 16% never smokers; 53% without emphysema on CT). The most common histologies were adenocarcinoma (242 [49%]), squamous (71 [14%]), undifferentiated (48 [10%]) and small cell carcinoma (42 [8%]). The presence of emphysema was associated with increased odds of squamous (OR 3.1; 95% CI 1.8-5.3) and small cell (OR 2.1; 95% CI 1.1-4.1) carcinoma. After adjustment for age, sex, COPD and smoking history, emphysema was associated with squamous (adjusted OR 2.6; 95% CI 1.4-4.8) but not small cell (adjusted OR 1.5; 95% CI 0.76-3.1) carcinoma. Sensitivity analysis was performed by sequential censoring of each histologic subtype yielding similar results. Adenocarcinoma was less common in the presence of emphysema relative to squamous and small cell carcinoma (adjusted OR 0.62; 95% CI 0.41-0.92). When these latter histologies were censored, no significant association between adenocarcinoma and emphysema was observed (adjusted OR 1.0; 95% CI 0.49-2.1).nnnCONCLUSIONSnRelative to other histologic subtypes, the odds of squamous carcinoma were significantly increased among lung cancer patients with emphysema after adjustment for age, sex, COPD and smoking history. Other common subtypes were not independently associated with emphysema.

Comparison of the Yield of Different Diagnostic Procedures for Cellular Differentiation and Genetic Profiling of Non–Small-Cell Lung Cancer

Introduction: As treatments for non–small-cell lung cancer (NSCLC) become personalized, cellular and molecular differentiation of the tumor is becoming the standard of care. Our objective is to compare the yield of different diagnostic procedures for cellular differentiation of NSCLC and analysis of epidermal growth factor receptor (EGFR) mutation. Methods: We evaluated all patients diagnosed with NSCLC from January 2004 to September 2010 at the Jewish General Hospital, Montreal. Diagnostic procedures included surgical biopsies, nonsurgical histologic biopsies (endobronchial and core needle), transbronchial needle aspirate (TBNA) and transthoracic needle aspirate (TTNA), bronchoalveolar lavage (BAL), and pleural fluid samples. Results: We included 702 subjects investigated for histopathologic differentiation of NSCLC. Of these, 269 were also investigated for EGFR mutation. Failure to ascertain the cellular subtype and EGFR mutation status was least likely with surgical specimens (0% and 1.8%, respectively); followed by TTNA (14% and 10%, respectively) and histologic biopsy (18% for both); and was frequent with TBNA (39% and 30%, respectively). Although BAL and pleural fluid specimens provided reasonable yield for cellular differentiation (20 % and 11%, respectively), their results were not accurate in 6% of their samples when compared with concurrent or subsequent surgical specimens (reference standard) performed in a subgroup of patients. Conclusion: Radiologically guided TTNA and histologic biopsies provided high yield for both molecular and histologic analyses. The yield of unguided TBNA was relatively low. Further studies are needed to assess the adequacy of BAL and pleural fluid samples for EGFR mutation analysis and accurate characterization of cellular subtypes of NSCLC.

Does Granulocyte Colony–Stimulating Factor Affect Survival in Patients with Advanced Non-small Cell Lung Cancer?

Background: Platinum-based chemotherapy is standard treatment for patients with advanced lung cancer. The common side effect of this therapy is myelosuppression, for which different stimulating factors are used. In this article, the effect of granulocyte colony–stimulating factor (G-CSF) administration on the survival of patients with unresectable non–small-cell lung cancer (NSCLC) was evaluated. Methods: The charts of 127 patients, treated with carboplatin-based chemotherapy, were reviewed for histology, stage, performance status, weight loss, treatment regimen, toxicity, and survival. Eighty patients were stage IIIA/IIIB NSCLC; 47 were stage IIIB (pleural effusion) or stage IV. Eighty-one patients (63%) experienced severe (grades 3 and 4) neutropenia. Forty-two patients received G-CSF, 37 patients for severe neutropenia (14 with febrile neutropenia) and five patients for active infection during chemotherapy. Results: Preliminary analyses, both unadjusted (median survival, 20 months versus 13.8 months; log-rank test, p = 0.02) and adjusted for covariates of interest (Cox regression, hazard ratio = 0.62, p = 0.03) showed a significant effect of the use of G-CSF on survival, even though the groups were balanced with respect to stage, performance status, weight loss, and dose intensity of chemotherapy. Patients with grades 3 and 4 neutropenia (whether they received G-CSF or not) had a better survival outcome compared to those who did not have neutropenia (median survival, 17.6 months versus 11.9 months, log-rank test, p = 0.04). A landmark analysis showed a marginally significant effect of G-CSF on survival (median survival, 18.6 months versus 15.1 months, log-rank test, p = 0.08), even after adjustment for covariates. The Cox regression with the use of G-CSF defined as a binary time-varying covariate also showed similar results (Cox regression, hazard ratio = 0.67, 95% CI: 0.42–1.04, p = 0.07). Conclusion: In this study, the time bias due to the delayed administration of G-CSF contributed to the longer survival of patients receiving G-CSF. Prospective studies are required to determine whether G-CSF has any effect on survival in patients with advanced NSCLC.

Cytology cell blocks are suitable for immunohistochemical testing for PD-L1 in lung cancer

BackgroundnPD-L1 immunohistochemistry (IHC) testing is usually carried out on tissue blocks from core needle biopsy or surgical resections. In this study, we assessed the feasibility of using cytology cell blocks for PD-L1 IHC assay.nnnMethodsnA total of 1419 consecutive cases of non-small-cell lung cancer (NSCLC), including 371 cytology cell blocks, 809 small biopsies, and 239 surgical specimens, were included in the study. The cytology cell blocks were prepared with formalin only, methanol/alcohol only or both. PD-L1 expression was examined by staining with Dako PD-L1 IHC 22C3 pharmDx kit. A Tumor Proportion Score (TPS) was categorized asu2009<1%, 1%-49% andu2009≥50% tumor cells. A total of 100 viable tumor cells were required for adequacy.nnnResultsnOf the cytology cell blocks, 92% of the specimens had an adequate number of tumor cells, not significantly different from small biopsies. The rate of TPS ≥50% differed between sample types and was observed in 42% of cytology cell blocks versus 36% of small biopsies (Pu2009=u20090.04), and 29% of surgical resections (Pu2009=u20090.001). The fixative methods did not affect the immunostaining, with overall PD-L1 high expression (TPS ≥50%) rates of 42% in formalin-fixed specimens versus 40% in specimens with combined fixation by methanol/alcohol and formalin (NS). The PD-L1 high expression rate was not associated with EGFR, ALK or KRAS molecular alterations. Higher stage (IV) was associated with higher PD-L1 TPS (P=u20090.001).nnnConclusionnOur results show that when the TPS ≥50% is used as the end point, PD-L1 IHC performs well with cytology cell blocks. Cell blocks should be considered as a valuable resource for PD-L1 testing in advanced NSCLC. The clinical significance of higher PD-L1 IHC scores in cytology specimens needs to be evaluated prospectively.