The Impact of Induction Chemotherapy and the Associated Tumor Response on Subsequent Radiation-Related Changes in Lung Function and Tumor Response

Abstract

Purpose-To assess the impact of induction chemotherapy, and associated tumor shrinkage, on the subsequent radiation-related changes in pulmonary function and tumor response.Methods and Materials-As part of a prospective IRB-approved study, 91 evaluable patients treated definitively with thoracic RT for unresectable lung cancer were analyzed. The rates of RTassociated pulmonary toxicity and tumor response were compared in the patients with and without pre-RT chemotherapy. In the patients receiving induction chemotherapy, the rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without a response (modified RECIST criteria) to the pre-RT chemotherapy. Comparisons of the rates of improvements in PFTs post-RT, dyspnea requiring steroids, and percent declines in PFTs post-RT were compared in patient subgroups using Fisher's exact test, analysis of variance, and linear or logistic regression.Results and conclusion-The use of pre-RT chemotherapy appears to increase the rate of radiation-induced pneumonitis (p=0.07-0.01), but has no consistent impact on changes in PFTs. The degree of induction-chemotherapy-associated tumor shrinkage is not associated with the rate of subsequent-RT-associated pulmonary toxicity. The degree of tumor response to chemotherapy is not related to the degree of tumor response to RT. Additional study is needed to better clarify this issue.

Association Between RT-Induced Changes in Lung Tissue Density and Global Lung Function

“…9, 17–20, 31. For example, we observed that patients with SPECT perfusion defects adjacent to a central mediastinal mass might have improved PFTs following RT 17.…”

“…Further, since prior analysis demonstrated that patients with large central tumors and adjacent hypoperfusion (based on pre-RT SPECT scan) have a ≈ 50% probability of experiencing improvements in PFTs post RT 17, analysis was repeated excluding these patients. Since there may be surgery- or chemotherapy-associated changes in lung density, the analysis was repeated in subgroups based on pre-RT surgery or chemotherapy 9, 18–20. Last, the analysis was repeated using recognized PFT cut-offs (FEV1 < 2L, ≥ 2L; DLCO < 60%, ≥ 60% predicted) 21, since pre-RT PFTs might be considered for clinical decisions in routine treatments.…”

“…The study of RT-induced lung injury is complicated by the multiple endpoints frequently considered (e.g., radiologic vs. symptomatic vs. functional) 4. Interpretation of the literature can be challenging since the reported frequency of injury is highly dependent on the endpoint considered 5–8, which may be impacted by potentially confounding clinical factors 9–12, and the association between the different endpoints is not entirely clear.…”

Combining multiple models to generate consensus: Application to radiation‐induced pneumonitis prediction

“…Chemotherapy has also been previously implicated in causing radiation pneumonitis. 5, 36,42,43 The fusion also extracted female sex and squamous cell histology as being predictive, though less influential than either chemotherapy or the two dose groups ͑Table III͒. Figure 4 appears to suggest that females undergoing pre-RT chemotherapy are more susceptible to radiation injury.…”

“…Patient and treatment characteristics are listed in Table I ͑subsets of this patient group have been analyzed previously 36,37 ͒. The patients were typically treated with either anterior-posterior primary beams delivering 40-45 Gy, followed by off-cord parallel opposed boost beams, or multiple noncoplanar, nonaxial beams.…”