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. 2022 Mar 2;14(5):1282.
doi: 10.3390/cancers14051282.

Evaluation of Microscopic Tumour Extension in Localized Stage Non-Small-Cell Lung Cancer for Stereotactic Radiotherapy Planning

Martin Schmitt  1 , Lucie Aussenac  2 , Joseph Seitlinger  3 , Véronique Lindner  2 , Georges Noël  1 , Delphine Antoni  1
Affiliations

Evaluation of Microscopic Tumour Extension in Localized Stage Non-Small-Cell Lung Cancer for Stereotactic Radiotherapy Planning

Martin Schmitt et al. Cancers (Basel). .

Abstract

Background: Stereotactic radiotherapy for localised stage non-small-cell lung carcinoma (NSCLC) is an alternative indication for patients who are inoperable or refuse surgery. A study showed that the microscopic tumour extension (ME) of NSCLC varied according to the histological type, which allowed us 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 tumours. Methods: We performed a retrospective analysis including patients with adenocarcinoma (ADC) or squamous cell carcinoma (SCC) of localised stage T1N0 or T2aN0 who underwent surgery. The ME was measured from this boundary. The profile of the type of tumour spread was also evaluated. Results: The margin required to cover the ME of a localised NSCLC with a 95% probability is 4.4 mm and 2.9 mm for SCC and ADC, respectively. A significant difference in the maximum distance of the ME between the tumour-infiltrating lymphocytes (TILs), 0−10% and 50−90% (p < 0.05), was noted for SCC. There was a significant difference in the maximum ME distance based on whether the patient had chronic obstructive pulmonary disease (COPD) (p = 0.011) for ADC. Multivariate analysis showed a statistically significant relationship between the maximum microextension distance and size with the shrinkage coefficient. Conclusion: This study definitively demonstrated that the ME depends on the pathology subtype of NSCLC. According to International Commission on Radiation Units and Measurements (ICRU) reports, 50, 62 and 83 CTV margins, proposed by these results, should be added to the GTV (Gross tumour volume). When stereotactic body radiation therapy is used, this approach should be considered in conjunction with the dataset and other margins to be applied.

Keywords: adenocarcinoma; non-small-cell lung carcinoma; squamous cell carcinoma; stereotactic body radiation therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Example of microinvasion measurement. (A). Tumour stained with hematoxylin and eosin and delineated with marker pen. (B). Microscopic tumour extension measured from the boundary between the tumour and healthy tissue to the most distant tumour cell using a micrometre.
Figure 2
Figure 2
Bland-Altmann plots. Radiologic size and histologic size with shrinkage coefficients for adenocarcinoma (A) and squamous cell carcinoma (B).
Figure 2
Figure 2
Bland-Altmann plots. Radiologic size and histologic size with shrinkage coefficients for adenocarcinoma (A) and squamous cell carcinoma (B).
Figure 3
Figure 3
Correlation between maximal distance microextension and tumour size for adenocarcinoma (A) and squamous cell carcinoma (B).
Figure 4
Figure 4
Decision tree according to histological type, COPD status and TIL rate to cover 95% of the distance of diffusion probability. ADC: adenocarcinoma; COPD: chronic obstructive pulmonary disease; CT: computed tomography; NSCLC: non-small-cell lung carcinoma; SCC: squamous cell carcinoma.
See this image and copyright information in PMC

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