Transformation Into Small Cell Lung Cancer : a Mode of Resistance to Treatment

An international multicentric retrospective collection of cases was performed between 2005 and 2017. A global e-mailing to a network of thoracic oncology centers in France and Italy called for the selection of retrospective cases. Consecutive non small cell lung cancer (NSCLC) patients with stage III or IV EGFR NSCLC with or without initial EGFR mutation with a secondary transformation to small cell lung cancer (SCLC) in participating centers in France and Italy were included. Patients with a previous history of SCLC or neuroendocrine tumor of the lung were excluded as well as patients with combined Small cell/ Non-small cell lung cancer on the initial pathology sample.

Study ethics approval was obtained on December 8th of 2015 (CECIC Rhône-Alpes-Auvergne, Clermont-Ferrand, IRB 5891). Anonymized data were collected at each center then centrally analyzed at the Albert Bonniot Institute, Inserm U 823, Grenoble Alpes University, in Grenoble, France.

The primary objective of this study was to analyze survival data after transformation to SCLC. The secondary objectives were to define: the epidemiological characteristics at the time of diagnosis of NSCLC, the histomolecular characteristics at the time of diagnosis of NSCLC and at the time of diagnosis of SCLC; the clinical characteristics at the time of diagnosis of NSCLC and SCLC and the treatment characteristics before and after transformation from NSCLC to SCLC.

All identified cases will be analyzed. This concerns about sixty two patients because the transformation into small cell lung cancer is a rare mechanism of resistance, it is for this reason that all the cases will be included in order to obtain the most exhaustive data possible.

Continuous variables were described as median (25%-75% interquartile range [IQR]) and categorical variables as number (%). Associations between categorical variables were compared using the chi-2 test or Fisher's exact test and those between continuous variables using the Wilcoxon test. Patients were followed until November of 2017. Overall survival (OS) is the time from the initial diagnosis of lung cancer to death and survival after SCLC transformation is from the rebiopsy to death. Kaplan-Meier plots of survival curves were compared between groups using the log-rank test. All tests were two-sided, and P values <0.05 were considered statistically significant. All statistical analyses were performed using SAS 9.3 (SAS Institute, Cary, NC, USA).

Inclusion criteria

• Patient with no history of small cell cancer or Neuroendocrine cancer
• Patients with non-small cell lung cancer at baseline, stage IIIB or IV
• Transformation during treatment of non small cell lung cancer, in small cell cancer proven by biopsy

Exclusion criteria

• History of small cell cancer or Neuroendocrine cancer
• Absence of histological evidence of the transformation into small cell lung cancer after treatment of non small cell lung cancer
• Patients with non-small cell lung cancer at initial biopsy, stage I, II, IIIA