Abstract

Martin Schmitt¹, Lucie Aussenac², Joseph Seitlinger³, Veronique Lindner⁴, Georges Noël⁵, Delphine Antoni⁵

¹Institut de cancérologie Strasbourg Europe , Radiotherapy department , Strasbourg, France; ²Hautepierre University Hospital, Pathology department , Strasbourg, France; ³Lorraine Heart and Vessel Institute, Thoracic Surgery Departement, Vandœuvre-lès-Nancy, France; ⁴Hautepierre University Hospital, Pathology Department, Strasbourg, France; ⁵Institut de cancérologie Strasbourg Europe, Radiotherapy department , Strasbourg, France

Stereotactic radiotherapy for localized stage Non Small Cell Lung Carcinoma (NSCLC) is an alternative indication for patients who are inoperable or refuse surgery. Local control, specific and overall survival rates are similar to surgery. A study showed that the microscopic tumor extension (ME) of NSCLC varied according to the histological type, which allowed to deduce adapted margins for the clinical target volume (CTV). However, to date no study has been able to define the most relevant margins for patients with stage 1 tumors. 

We realized a retrospective analysis including patients with adenocarcinoma (ADC) or squamous cell carcinoma (SCC) of localized stage T1N0 or T2aN0 operated at the Strasbourg University Hospitals. We analyzed preoperative chest scans, delineated target volumes and analyzed the boundary between tumor tissue and healthy tissue on the surgical specimens. ME was measured from this boundary. The profile of the type of tumor spread was also evaluated.

One hundred and twelve patients with ADC and 42 patients with SCC were analyzed. The margin required to cover the ME of a localized NSCLC with a 95% probability is 4.4 mm and 2.9 mm for SCC and ADC respectively. There is a significant difference in maximum distance of ME between the tumor infiltrating lymphocyte (TILs) 0-10% and 50-90% (p<0.05) for SCC. To cover 95% of the samples in the TILs 0-10%, 20-40% and 50-90% groups a margin of 4.97 mm, 2.13 mm and 0 mm respectively would be required. There is a significant difference in maximum ME distance depending on whether the patient has chronic obstructive pulmonary disease (COPD) or not (p = 0.011) for ADC. To cover 95% of the ADC sample with COPD, a margin of 3.74 mm would be required. To cover 95% of the ADC sample without COPD, a margin of 2.27 mm would be required.

CTV margins of 8 mm and 6 mm for ADC and SCC respectively seem too large, however the absence of CTV margins in view of our results does not seem wise. We propose a decision tree to assist in the application of margins according to histologic type, COPD status and TILs rate. This approach should be considered in conjunction with the data set and other margins to be applied when stereotactic body radiation therapy is used.