Early FDG-PET imaging after radical radiotherapy for non-small cell lung cancer: Inflammatory changes in normal tissues correlate with tumor response and do not confound therapeutic response evaluation

Abstract

Purpose/ObjectiveTo investigate the relationship between PET-detected inflammatory changes in irradiated normal tissues and metabolic response at tumor sites in patients receiving radical radiotherapy (RRT) or chemo/RT for non-small cell lung cancer (NSCLC). The prognostic significance of these changes was also studied. We have previously reported that metabolic response powerfully predicts survival.Materials/MethodsIn 73 consecutive patients 18F-FDG PET was performed at a median of 70 days after completion of RRT or chemo/RT (60 Gy in 6 weeks in all but 2 cases, with concurrent platinum based chemotherapy in 60 cases). Radiation-induced inflammatory change was scored for normal tissues within the RT volume using a 0–3 grading scale as follows; Grade 0- No abnormality identified in normal tissues within the RT volume. Grade 1-Increased activity in the pleural reflections and soft tissues within the RT volume but no parenchymal lung changes. Grade 2-Increased parenchymal lung uptake in the radiation treatment volume of equal or lower intensity than normal soft tissues in the mediastinum or chest wall located outside the radiation field. Grade 3-Increased parenchymal lung uptake in the radiation treatment volume of greater intensity than normal soft tissues in the mediastinum or chest wall. Metabolic tumor response was assessed using a pattern-recognition algorithm comparing pre- and post-treatment scans. Prognostic significance of inflammatory changes was tested using the Cox proportional hazards regression model.ResultsIncreased FDG uptake in normal tissues (radiotoxicity) was associated with a greater likelihood of complete or partial metabolic tumor response on both PET (p = 0.0044) and CT (p = 0.029): 95% of patients with grade 2 or 3 uptake achieved a complete or partial metabolic response compared with 70% of patients with grade 0 or 1 uptake. The degree of prognostic stratification provided by metabolic response was unaffected by the presence of significant normal tissue uptake (p = 0.98, test for interaction). PET response provided significant prognostic stratification for patients both with and without significant normal tissue uptake, with estimated hazard ratios of 1.9 (95% CI:1.2–3.2) and 2.1 (95% CI:1.0–4.0) respectively associated with each decrease in tumor response category from complete metabolic response to progressive metabolic disease.ConclusionsInflammatory changes in normal tissues are commonly detected by FDG-PET after thoracic RT and have been considered an impediment to tumor response assessment. Our results indicate that these changes are positively correlated with tumor response, suggesting that tumor radioresponsiveness and normal tissue radiosensitivity may be linked. Prognostic stratification provided by PET does not appear to be compromised by inflammatory changes in lung and pleura if a meticulous visual response assessment technique is used Purpose/ObjectiveTo investigate the relationship between PET-detected inflammatory changes in irradiated normal tissues and metabolic response at tumor sites in patients receiving radical radiotherapy (RRT) or chemo/RT for non-small cell lung cancer (NSCLC). The prognostic significance of these changes was also studied. We have previously reported that metabolic response powerfully predicts survival. To investigate the relationship between PET-detected inflammatory changes in irradiated normal tissues and metabolic response at tumor sites in patients receiving radical radiotherapy (RRT) or chemo/RT for non-small cell lung cancer (NSCLC). The prognostic significance of these changes was also studied. We have previously reported that metabolic response powerfully predicts survival. Materials/MethodsIn 73 consecutive patients 18F-FDG PET was performed at a median of 70 days after completion of RRT or chemo/RT (60 Gy in 6 weeks in all but 2 cases, with concurrent platinum based chemotherapy in 60 cases). Radiation-induced inflammatory change was scored for normal tissues within the RT volume using a 0–3 grading scale as follows; Grade 0- No abnormality identified in normal tissues within the RT volume. Grade 1-Increased activity in the pleural reflections and soft tissues within the RT volume but no parenchymal lung changes. Grade 2-Increased parenchymal lung uptake in the radiation treatment volume of equal or lower intensity than normal soft tissues in the mediastinum or chest wall located outside the radiation field. Grade 3-Increased parenchymal lung uptake in the radiation treatment volume of greater intensity than normal soft tissues in the mediastinum or chest wall. Metabolic tumor response was assessed using a pattern-recognition algorithm comparing pre- and post-treatment scans. Prognostic significance of inflammatory changes was tested using the Cox proportional hazards regression model. In 73 consecutive patients 18F-FDG PET was performed at a median of 70 days after completion of RRT or chemo/RT (60 Gy in 6 weeks in all but 2 cases, with concurrent platinum based chemotherapy in 60 cases). Radiation-induced inflammatory change was scored for normal tissues within the RT volume using a 0–3 grading scale as follows; Grade 0- No abnormality identified in normal tissues within the RT volume. Grade 1-Increased activity in the pleural reflections and soft tissues within the RT volume but no parenchymal lung changes. Grade 2-Increased parenchymal lung uptake in the radiation treatment volume of equal or lower intensity than normal soft tissues in the mediastinum or chest wall located outside the radiation field. Grade 3-Increased parenchymal lung uptake in the radiation treatment volume of greater intensity than normal soft tissues in the mediastinum or chest wall. Metabolic tumor response was assessed using a pattern-recognition algorithm comparing pre- and post-treatment scans. Prognostic significance of inflammatory changes was tested using the Cox proportional hazards regression model. ResultsIncreased FDG uptake in normal tissues (radiotoxicity) was associated with a greater likelihood of complete or partial metabolic tumor response on both PET (p = 0.0044) and CT (p = 0.029): 95% of patients with grade 2 or 3 uptake achieved a complete or partial metabolic response compared with 70% of patients with grade 0 or 1 uptake. The degree of prognostic stratification provided by metabolic response was unaffected by the presence of significant normal tissue uptake (p = 0.98, test for interaction). PET response provided significant prognostic stratification for patients both with and without significant normal tissue uptake, with estimated hazard ratios of 1.9 (95% CI:1.2–3.2) and 2.1 (95% CI:1.0–4.0) respectively associated with each decrease in tumor response category from complete metabolic response to progressive metabolic disease. Increased FDG uptake in normal tissues (radiotoxicity) was associated with a greater likelihood of complete or partial metabolic tumor response on both PET (p = 0.0044) and CT (p = 0.029): 95% of patients with grade 2 or 3 uptake achieved a complete or partial metabolic response compared with 70% of patients with grade 0 or 1 uptake. The degree of prognostic stratification provided by metabolic response was unaffected by the presence of significant normal tissue uptake (p = 0.98, test for interaction). PET response provided significant prognostic stratification for patients both with and without significant normal tissue uptake, with estimated hazard ratios of 1.9 (95% CI:1.2–3.2) and 2.1 (95% CI:1.0–4.0) respectively associated with each decrease in tumor response category from complete metabolic response to progressive metabolic disease. ConclusionsInflammatory changes in normal tissues are commonly detected by FDG-PET after thoracic RT and have been considered an impediment to tumor response assessment. Our results indicate that these changes are positively correlated with tumor response, suggesting that tumor radioresponsiveness and normal tissue radiosensitivity may be linked. Prognostic stratification provided by PET does not appear to be compromised by inflammatory changes in lung and pleura if a meticulous visual response assessment technique is used Inflammatory changes in normal tissues are commonly detected by FDG-PET after thoracic RT and have been considered an impediment to tumor response assessment. Our results indicate that these changes are positively correlated with tumor response, suggesting that tumor radioresponsiveness and normal tissue radiosensitivity may be linked. Prognostic stratification provided by PET does not appear to be compromised by inflammatory changes in lung and pleura if a meticulous visual response assessment technique is used