Lung cancer is one of the most common and lethal types of cancer, accounting for 17% of the total new cancer cases and approximately one-fourth of the total cancer-related deaths worldwide (1). Non-small-cell lung cancer (NSCLC) includes adenocarcinoma, squamous cell carcinoma and large-cell carcinoma and is responsible for ~85% of newly diagnosed lung cancer cases (2). Approximately 80% of lung cancer cases have already advanced at the time of diagnosis, thus eliminating surgery as a treatment option. Multidisciplinary treatment is currently the main therapeutic approach for advanced NSCLC. The main method to quickly and effectively control tumor growth is a combination of local treatment and systemic therapy (3). However, the clinical outcomes for radiotherapy combined with chemotherapy, the main therapeutic regimen for advanced NSCLC under the traditional multidisciplinary approach, have been disappointing, with a 5-year survival rate of <20% (4–6).

With the increase of the application of targeted therapy for lung cancer, the combination of targeted therapy and radiotherapy has also become a popular therapeutic modality. Theoretically, due to its low toxicity, the combination regimen may be an effective approach, particularly suitable for elderly patients and those with additional underlying diseases (7,8).

However, certain specifications that have been traditionally used for chemotherapy may not be applicable to targeted therapy. Unless disease progresses significantly during the course of targeted therapy, the general recommendation is to continue medication without interruption, as treatment termination is likely to result in rapid disease progression (9). Nishie et al (9) reported a statistically significant difference in the median survival of NSCLC patients who continued epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and those who discontinued such therapy after disease progression, indicating that the management strategy of targeted therapy should be differentiated from that of radiotherapy or chemotherapy.

Stereotactic body radiation therapy (SBRT) delivers high doses of radiation to the involved target field and diminishes the radiation fields by reducing the effects of tumor motion for accuracy and precision, thus contributing to a reduction in the volume of irradiation of normal tissues and an increase in the dose delivered to the target field (10). SBRT was recently used for lung cancer in patients for whom surgery is not a suitable option, with an efficacy comparable to that of surgery for early lung cancer (11). Rowe et al (12) expanded SBRT to central lung cancer and reported that the approach was safe and effective, with mostly tolerable early complications. However, late complications were not addressed in that study. In this study, we report the development of severe obstructive atelectasis as a late complication in two patients with central lung cancer who received SBRT. The obstructive atelectasis interrupted the evaluation of the efficacy of the subsequent gefitinib treatment for NSCLC. Informed consent was obtained from the two patients prior to the study. This study was approved by the Ethics Committee of Daping Hospital [(2012)NO.10].

As interstitial pneumonia is one of the most severe side effects of EGFR-TKIs and radiotherapy, EGFR-TKIs and concurrent radiotherapy have been used with caution in clinical practice. Wang et al (13) reported only a low incidence rate (4%) of third-degree radiation pneumonitis in NSCLC patients receiving EGFR-TKI treatment plus radiotherapy. Okamoto et al (6), however, reported radiation pneumonitis in 2 of 7 stage III unresectable NSCLC patients. Onal et al (14) also reported on a patient who received erlotinib after radiotherapy, which induced radiation pneumonitis. Due to the aforementioned reasons, combination therapy was not prescribed for our two patients. Rather, additional EGFR-TKI treatment was administered sequentially after the completion of radiotherapy.

The main advantage of SBRT is its short radiation time and less damage to the surrounding tissues, resulting in a decreased risk of radiation pneumonitis in lung cancer. Wang et al (15) reported that in 14 patients with advanced NSCLC, SBRT combined with gefitinib resulted in a disease remission rate of up to 57.1%. The median time of disease remission was 8 months, while the 1-year survival rate was 69.6%, suggesting that this regimen may improve local control and disease remission rates with few side effects. Compared to 3D-RT or intensity-modulated radiotherapy, SBRT in combination with EGFR-TKIs may be a more suitable treatment option for elderly patients or those with diseases that are a contraindication to radiotherapy, such as chronic obstructive pulmonary disease (16).

However, our two patients with central lung lesions developed severe obstructive atelectasis while on gefitinib after undergoing SBRT, which interrupted our evaluation of gefitinib efficacy. Our analysis indicated that the occurrence of obstructive atelectasis mainly resulted from SBRT for lesions located in the hilum of the lung, which caused the late complication of radioactive bronchial fibrosis, in turn leading to bronchial stenosis. However, such severe obstructive atelectasis cannot exclude the synergistic role of gefitinib. Due to the misjudgement of obstructive atelectasis as a result of disease progression in Case 1, gefitinib was wrongly terminated after 2 weeks, depriving the patient of the opportunity to receive effective treatment. Case 2 was slightly more complicated. The patient did not undergo any gene mutation detection tests. The clinical trial from IPASS (17), suggested that the majority of the patients developed drug resistance within 6–8 months of taking the medication. This patient developed atelectasis exactly 7 months after gefitinib initiation. A PET-CT examination confirmed that there was no progression of the original lesions. Hence, we did not adopt the suggestion by outpatient physicians to discontinue the medication. In fact, Takeda et al (18) reported that, for patients with NSCLC after SBRT, the SUV from PET-CT are of higher diagnostic value regarding local recurrence compared to those from CT.

Our experience with patients who have recently undergone radiotherapy suggests that, if disease progression occurs at the site of radiotherapy during the course of EGFR-TKI treatment, the decision to discontinue the medication should be based on PET-CT rather than CT alone. Furthermore, radioactive atelectasis differs from radiation pneumonitis. If the patient is able to tolerate the condition without severe breathing difficulties, the recommendation is to continue medication. However, our empirical findings must be substantiated and confirmed through further clinical trials.