Early Identification of Pneumonitis in Patients Irradiated for Lung Cancer-Final Results of the PARALUC Trial.

Radiotherapy of lung cancer may cause pneumonitis that generally occurs weeks or months following therapy and can be missed. This prospective trial aimed to pave the way for a mobile application (app) allowing early diagnosis of pneumonitis. The primary goal was the identification of the optimal cut-off of a score to detect pneumonitis of grade ≥2 after radiotherapy for lung cancer. Based on the severity of symptoms (cough, dyspnea, fever), scoring points were 0−9. Receiver operating characteristic (ROC)-curves were used to describe the sensitivity and specificity. The area under the ROC-curve (AUC) was calculated to judge the accuracy of the score, Youden-index was employed to define the optimal cut-off. Until trial termination, 57 of 98 patients were included. Eight of 42 patients evaluable for the primary endpoint (presence or absence of radiation pneumonitis) experienced pneumonitis. AUC was 0.987 (0.961−1.000). The highest sensitivity was achieved with 0−4 points (100%), followed by 5 points (87.5%), highest specificity with 5−6 points (100%). The highest Youden-index was found for 5 points (87.5%). The rate of patient satisfaction with the symptom-based scoring system was 93.5%. A cut-off of 5 points was identified as optimal to differentiate between pneumonitis and no pneumonitis. Moreover, pneumonitis was significantly associated with an increase of ≥3 points from baseline (p < 0.0001). The scoring system provided excellent accuracy and high patient satisfaction. Important foundations for the development of a mobile application were laid.

Prognostic Factors of Survival After Radiotherapy for Lung Cancer-The Impact of Smoking Pack Years.

BACKGROUND/AIM: The prognostic role of smoking pack years after thoracic irradiation for lung cancer needs further clarification, since previous studies showed conflicting results. Therefore, this study investigated potential prognostic factors for survival including pack years in 170 lung cancer patients receiving local radiotherapy. PATIENTS AND METHODS: Twelve factors were retrospectively evaluated for survival including age, sex, tumor site, histology, primary tumor stage, nodal stage, distant metastasis, radiation dose, upfront surgery or systemic treatment, pulmonary function, and number of pack years. RESULTS: On univariate analyses, absence of distant metastasis (p=0.049), radiation dose >56 Gy (p=0.019), and ≤40 pack years (p=0.005) were significantly associated with better survival. In the multivariate analysis, number of pack years (hazard ratio 2.18, 95% confidence interval 1.25-3.82, p=0.006) maintained significance; distant metastasis (p=0.34) and radiation dose (p=0.16) were not significant. CONCLUSION: Number of pack years was an independent predictor of survival after thoracic irradiation for lung cancer.

Estimating the Probability of Not Completing the Intended Course of Thoracic Radiotherapy for Lung Cancer.

BACKGROUND/AIM: In some patients with lung cancer scheduled for thoracic radiotherapy (RT), treatment is discontinued before reaching the planned dose. For optimal treatment personalization, a tool estimating whether a patient can complete radiotherapy would be helpful. PATIENTS AND METHODS: Eleven pre-RT characteristics were analyzed in 170 patients receiving local RT for lung cancer. Characteristics included age, sex, tumor site, histology, tumor and nodal stage, distant metastasis, surgery, systemic treatment, pulmonary function, and smoking history. RESULTS: Age >75 years (p=0.038), distant metastasis (p=0.009), and forced expiratory volume in 1 second <1.2 l (p=0.038) were significantly associated with discontinuation of RT. A prognostic instrument was developed in 126 patients with complete data regarding these characteristics. It included three groups (0, 1, and 2-3 points) with non-completion rates of 33.3%, 55.0% and 75.0% (p=0.004). CONCLUSION: This new instrument can help estimating the probability that lung cancer patients assigned to local RT cannot complete the planned course of RT.

A Prognostic Tool to Estimate the Risk of Pneumonitis in Patients Irradiated for Lung Cancer.

BACKGROUND/AIM: Radiotherapy of lung cancer can lead to pneumonitis. This study aimed to identify risk factors and create a prognostic tool. PATIENTS AND METHODS: Sixteen factors were evaluated in 169 patients irradiated for lung cancer including age, sex, lung function, primary tumor/nodal stage, histology, tumor location, surgery, systemic treatment, radiation volume, total dose, mean dose to ipsilateral lung, history of another malignancy, pack years, chronic inflammatory disease, and cardiovascular disease. RESULTS: Forty-one patients experienced pneumonitis. Significant associations were found for total doses >56 Gy (p=0.023), mean lung doses >20 Gy (p=0.002) or >13 Gy (p<0.001), and chronic inflammatory disease (p=0.034). Considering mean lung dose and chronic inflammatory disease, scores were 2, 3, 4, or 5 points. Pneumonitis rates were 0% (0/35), 24% (14/58), 32% (21/66), and 60% (6/10) (p=0.001), respectively. CONCLUSION: Based on significant risk factors, a prognostic tool was developed that can help estimate the risk of pneumonitis and contribute to personalized follow up of patients.

Pneumonitis after radiotherapy for lung cancer (PARALUC): an interventional study to create a symptom-based scoring system for identification of patients developing radiation pneumonitis.

BACKGROUND: Pneumonitis is a possible side effect of radiotherapy for lung cancer. Since it can occur up to several months following treatment, symptoms may not be associated with previous radiotherapy, and pneumonitis can become severe before diagnosed. This study aimed to develop a symptom-based scoring system to contribute to earlier detection of radiation pneumonitis requiring medical intervention (grade ≥ 2). METHODS: Patients irradiated for lung cancer complete a paper-based questionnaire (symptom-based score) during and up to 24 weeks following radiotherapy. Patients rate symptoms potentially associated with pneumonitis, and scoring points are assigned to severity of these symptoms. Sum scores are used to identify radiation pneumonitis. If radiation pneumonitis is suspected, patients undergo standard diagnostic procedures. If grade ≥ 2 pneumonitis is confirmed, medical intervention is indicated. The discriminative power of the score will be assessed by calculating the area under the receiver operating characteristic curve (AUC). If statistical significance of the AUC is reached, the optimal sum score to predict radiation pneumonitis will be established, which is defined as a cut-off value with sensitivity ≥90% and specificity ≥80%. Assuming a ratio between patients without and with pneumonitis of 3.63, a sample size of 93 patients is required in the full analysis set to yield statistical significance at the level of 5% with a power of 90% if the AUC under the alternative hypothesis is at least 0.9. Considering potential drop-outs, 98 patients should be recruited. If > 20% of patients are not satisfied with the score, modification is required. If the dissatisfaction rate is > 40%, the score is considered not useful. In 10 patients, functionality of a mobile application will be tested in addition to the paper-based questionnaire. DISCUSSION: If an optimal cut-off score resulting in sufficiently high sensitivity and specificity can be identified and the development of a symptom-based scoring system is successful, this tool will contribute to better identification of patients experiencing pneumonitis after radiotherapy for lung cancer. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT04335409 ); registered on 2nd of April, 2020.

Prevalence and Characteristics of Symptomatic Pneumonitis After Radiotherapy of Patients With Locally Advanced Lung Cancer.

BACKGROUND/AIM: Radiotherapy of locally advanced lung cancer often requires high doses potentially leading to pneumonitis. This study evaluated the rate of symptomatic pneumonitis and characteristics in these patients. PATIENTS AND METHODS: This study included 278 patients irradiated for locally advanced lung cancer between 2016 and 2019. In patients experiencing symptomatic pneumonitis, patient and treatment characteristics were analyzed. RESULTS: Pneumonitis was diagnosed in 21 patients (7.6%) after a median of 9 (1-23) weeks. Ipsilateral lungs received mean doses >13 Gy in 21 (100%) and >20 Gy in 15 patients (71.4%). Seventeen patients (81.0%) received chemotherapy and/or immunotherapy, 12 (57.1%) had significant cardiovascular disease (all 21 patients had risk factors), 11 (52.4%) were heavy smokers (≥40 pack years), 7 (33.3%) were aged ≥74 years, 5 (23.8%) had chronic inflammatory disease and 4 (19.0%) had previous tumors. CONCLUSION: Overall pneumonitis rate was 7.6%. Frequent characteristics included high mean lung doses, systemic treatment, cardiovascular disease (and risk factors), heavy smoking, older age, chronic inflammatory disease and history of a previous tumor.