Dosimetric Predictors of Radiotherapy-Induced Lymphocytopenia in Lung Cancer.

Abstract

We read with interest the study by Abravan et al.1Abravan A. Faivre Finn C. Kennedy J. McWilliam A. van Herk M. Radiotherapy-related lymphopenia affects overall survival in patients with lung cancer. J Thorac Oncol.https://doi.org/10.1016/j.jtho.2020.06.008Google Scholar on the dosimetric predictors of radiotherapy-induced lymphopenia in lung cancer. The prognostic effect of posttreatment lymphocytopenia and its correlation with integral dose in lung cancer has been reported previously in our study conducted in the same institution.2Joseph N. McWilliam A. Kennedy J. et al.Post-treatment lymphocytopaenia, integral body dose and overall survival in lung cancer patients treated with radical radiotherapy.Radiother Oncol. 2019; 135: 115-119Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar Although the study is of interest, we believe that there are aspects that are open to further discussion. Lymphocyte nadir may be reached at different time points and, as stated by the authors, could be transient with recovery during treatment.1Abravan A. Faivre Finn C. Kennedy J. McWilliam A. van Herk M. Radiotherapy-related lymphopenia affects overall survival in patients with lung cancer. J Thorac Oncol.https://doi.org/10.1016/j.jtho.2020.06.008Google Scholar Because white cell counts or neutrophil counts were not analyzed separately, the possibility that lymphocyte nadir was accompanied by panleucopenia in some patients has not been excluded. The lack of temporal precision of nadir count is relevant because in the analysis of dosimetric variables, the dose delivered for the whole course of treatment, including the component delivered after reaching nadir, was considered. We believe that some of these pitfalls could have been avoided if posttreatment lymphocyte count had been selected for analysis. Apart from temporal precision, posttreatment counts may be of greater importance because consolidation with immunotherapy after radiotherapy has proven efficacy in this setting.3Antonia S.J. Villegas A. Daniel D. et al.Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC.N Engl J Med. 2018; 379: 2342-2350Crossref PubMed Scopus (1216) Google Scholar Furthermore, analysis of lymphocyte count as a dichotomous rather than a continuous variable oversimplifies the data, risking an underestimation of the effect of variation within the study. The mean heart dose and mean lung dose emerged as the most robust dosimetric predictors of lymphopenia, and the authors suggested that “irradiation of circulating blood volume is the most important mechanism of lymphopenia.”1Abravan A. Faivre Finn C. Kennedy J. McWilliam A. van Herk M. Radiotherapy-related lymphopenia affects overall survival in patients with lung cancer. J Thorac Oncol.https://doi.org/10.1016/j.jtho.2020.06.008Google Scholar These findings are in conformity with our previous study.2Joseph N. McWilliam A. Kennedy J. et al.Post-treatment lymphocytopaenia, integral body dose and overall survival in lung cancer patients treated with radical radiotherapy.Radiother Oncol. 2019; 135: 115-119Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar We chose the integral dose, defined as the product of mean body dose and body volume, as the dosimetric predictor given that it encompasses both low-dose and high-dose regions (including doses to heart and lung) in a single robust parameter.2Joseph N. McWilliam A. Kennedy J. et al.Post-treatment lymphocytopaenia, integral body dose and overall survival in lung cancer patients treated with radical radiotherapy.Radiother Oncol. 2019; 135: 115-119Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar Interestingly the authors also reported a correlation with the volume of thoracic vertebrae receiving 20 Gy or higher (V20) and suggested a threshold effect for this parameter.1Abravan A. Faivre Finn C. Kennedy J. McWilliam A. van Herk M. Radiotherapy-related lymphopenia affects overall survival in patients with lung cancer. J Thorac Oncol.https://doi.org/10.1016/j.jtho.2020.06.008Google Scholar However, we noted in the illustration of correlation coefficients that the mean thoracic vertebral dose achieved a coefficient close to that of V20.1Abravan A. Faivre Finn C. Kennedy J. McWilliam A. van Herk M. Radiotherapy-related lymphopenia affects overall survival in patients with lung cancer. J Thorac Oncol.https://doi.org/10.1016/j.jtho.2020.06.008Google Scholar Indeed, for all three structures, the correlation coefficients are worse with extreme dosimetric parameters and better with moderate ones.1Abravan A. Faivre Finn C. Kennedy J. McWilliam A. van Herk M. Radiotherapy-related lymphopenia affects overall survival in patients with lung cancer. J Thorac Oncol.https://doi.org/10.1016/j.jtho.2020.06.008Google Scholar Therefore, although thoracic vertebrae V20 did achieve a numerically better correlation coefficient than the mean dose, this may not signify a threshold effect. The integral dose would also encompass the dose to thoracic vertebrae and, therefore, the three significant dosimetric predictors would be captured by the integral dose in a single parameter.2Joseph N. McWilliam A. Kennedy J. et al.Post-treatment lymphocytopaenia, integral body dose and overall survival in lung cancer patients treated with radical radiotherapy.Radiother Oncol. 2019; 135: 115-119Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar Although the model was validated in a cohort of patients with esophageal cancer, there are differences between them and patients with lung cancer. Quite distinct from the anatomical variability of lung tumors, which could be central and peripheral in addition to being affected by laterality, the esophagus and its tumors are cylindrical structures that lie in the midline between the heart, lungs, and vertebrae. It stands to reason that any dosimetric comparison of dose among these organs will be affected more by tumor volume in esophageal tumors than in lung cancer. It is, therefore, imperative that the model undergoes proper validation in an independent cohort of patients with lung cancer. In conclusion, we commend the authors for this very interesting study and look forward to further work in this exciting space exploring the effects of radiation on the systemic immune system. Prof. Choudhury thanks the National Institute for Health Research Manchester Biomedical Research Centre for their support. Radiotherapy-Related Lymphopenia Affects Overall Survival in Patients With Lung CancerJournal of Thoracic OncologyVol. 15Issue 10PreviewLymphopenia after radiotherapy has an adverse effect on the patient’s outcome. However, the relationship between radiotherapy dose delivery and lymphopenia is not fully understood. This work used image-based data mining to identify anatomical regions where the received dose is correlated with severe lymphopenia. Full-Text PDF Open Archive