Association Between Pulmonary Uptake of Fluorodeoxyglucose Detected by Positron Emission Tomography Scanning After Radiation Therapy for Non–Small-Cell Lung Cancer and Radiation Pneumonitis

Purpose

To study the relationship between fluorodeoxyglucose (FDG) uptake in pulmonary tissue after radical radiation therapy (RT) and the presence and severity of radiation pneumonitis.

Methods and Materials

In 88 consecutive patients, ¹⁸F-FDG–positron emission tomography was performed at a median of 70 days after completion of RT. Patients received 60 Gy in 30 fractions, and all but 15 had concurrent platinum-based chemotherapy. RT-induced pulmonary inflammatory changes occurring within the radiation treatment volume were scored, using a visual (0 to 3) radiotoxicity grading scale, by an observer blinded to the presence or absence of clinical radiation pneumonitis. Radiation pneumonitis was retrospectively graded using the Radiation Therapy Oncology Group (RTOG) scale by an observer blinded to the PET radiotoxicity score.

Results

There was a significant association between the worst RTOG pneumonitis grade occurring at any time after RT and the positron emission tomograph (PET) radiotoxicity grade (one-sided p = 0.033). The worst RTOG pneumonitis grade occurring after the PET scan was also associated with the PET radiotoxicity grade (one-sided p = 0.035). For every one-level increase in the PET toxicity scale, the risk of a higher RTOG radiation pneumonitis score increased by approximately 40%. The PET radiotoxicity score showed no significant correlation with the duration of radiation pneumonitis.

Conclusions

The intensity of FDG uptake in pulmonary tissue after RT determined using a simple visual scoring system showed significant correlation with the presence and severity of radiation pneumonitis. ¹⁸F-FDG–PET may be useful in the prediction, diagnosis and therapeutic monitoring of radiation pneumonitis.

Introduction

Tumor response assessment after radiation therapy (RT) or chemo-RT has historically been made using computed tomography (CT). We have previously reported that fluorodeoxyglucose–positron emission tomography (FDG-PET) is superior to CT for response assessment after radical chemo-RT for non–small-cell lung cancer (NSCLC) (1), and that PET response is strongly correlated with survival and patterns of relapse (2). Other groups have reported that FDG-PET can provide important prognostic information on tumor response in NSCLC and other malignancies (3). FDG-PET scans performed after RT or chemo-RT for NSCLC may detect changes in normal tissues (4). These changes include increased FDG uptake in pleura and lung parenchyma compared with baseline scans, and we have previously reported that these changes can be graded using a simple visual “radiotoxicity” scale (Table 1) (4). The presence of FDG uptake in normal lung did not prevent a post- treatment FDG-PET scan from providing valuable prognostic information on tumor response after RT using qualitative reporting but could potentially confound automated evaluation using standardized uptake value (SUV) analysis. In that study, we presumed that FDG uptake in previously normal lung was due to radiation pneumonitis but did not investigate the potential correlation between a visual assessment of FDG uptake and symptoms and signs of pneumonitis.

Radiation pneumonitis is a relatively common and potentially life-threatening complication that is most likely to occur in patients who receive high doses of radiation to large volumes of lung. It normally occurs in the first few months after RT, and can cause symptoms ranging in severity from mild cough to overwhelming dyspnea and fatal respiratory failure. It is characterized by cough, dyspnea, and the presence of chraracteristic radiological abnormalities, most prominent in but not always confined to the radiation ports (5). Radiation pneumonitis is often treated with corticosteroids (6), and steroid use is itself a component in the widely used Radiation Therapy Oncology Group (RTOG) grading system. Diagnosis and management of pneumonitis is complicated by the fact that many lung cancer patients have pre-existing lung disease, most commonly chronic obstructive pulmonary disease (COPD), which can cause cough and dyspnea and is associated with acute exacerbations caused by infection. Respiratory symptoms after RT may be due to one or more pathologic conditions occurring simultaneously, including radiation pneumonitis, COPD, and infection. FDG-PET has the potential to help diagnose and manage pneumonitis. The primary aim of this study was to investigate the possible relationship between a visual assessment of FDG uptake in previously normal lung or pleura after RT and the risk of radiation pneumonitis. Because it is a straightforward method that does not require coregistration of pre- and posttreatment PET scans or detailed correlative regional SUV assessments, a visual toxicity scale could potentially be used as a diagnostic tool in community practice.