Lung cancer is a leading cause of cancer-related death globally, with a significant portion of patients presenting with stage III non-small cell lung cancer (NSCLC). Concurrent chemoradiotherapy has been the standard of care, but the PACIFIC trial demonstrated that adding Durvalumab significantly improved progression-free and overall survival. However, Durvalumab's unavailability in Lebanon led to the use of Atezolizumab, a drug with a similar mechanism of action, in this study. This paper investigates the incidence of pneumonitis, a known adverse effect of these immunotherapies, in a cohort of stage III NSCLC patients receiving Atezolizumab after concurrent chemoradiation.

Concurrent chemoradiotherapy has been the established standard of care for unresectable stage III NSCLC, improving survival rates compared to sequential treatment. The PACIFIC trial highlighted the significant benefit of adding Durvalumab to concurrent chemoradiation, improving progression-free survival and overall survival. However, Durvalumab, like Atezolizumab, carries a risk of pneumonitis, a serious adverse event. Previous studies have explored the incidence and risk factors of pneumonitis in patients receiving immune checkpoint inhibitors, with some suggesting that squamous cell carcinoma histology might be associated with a higher risk. The rate of pneumonitis with anti-PD-1 agents is thought to be slightly higher than that with PD-L1 inhibitors, although more research is needed to confirm this.

This retrospective study analyzed data from the lung cancer registry at the American University of Beirut Medical Center. The study included 14 patients aged 18 or older diagnosed with stage III NSCLC who received Atezolizumab as consolidation therapy following concurrent chemoradiation therapy since January 2018. Data were collected from patients' medical records. Pneumonitis diagnosis relied on symptoms (cough, dyspnea, weight loss) and radiological findings (consolidation or ground-glass opacities), graded using CTCAE criteria (grades 1-5). The two-sample t-test (assuming unequal variances) was used to compare means of patient characteristics between patients with and without pneumonitis. PD-L1 status, age, gender, smoking status, and histology were analyzed as potential predictive factors for pneumonitis development.

Of the 14 patients, 8 (57.1%) developed pneumonitis. There was no significant association between pneumonitis and age (p=0.98), gender (p=1), or smoking status (p=0.86). The impact of PDL-1 status could not be definitively assessed due to the small sample size and missing data. Histology showed a trend towards higher pneumonitis incidence in patients with squamous cell carcinoma (all 5 patients developed pneumonitis), although this did not reach statistical significance (p=0.078). The mean onset of pneumonitis was 3.62 months after completing chemoradiation and 2.45 months after starting Atezolizumab. Grade 1 pneumonitis was detected later (on average 4.76 months after the end of chemoradiotherapy and 3.62 months after starting Atezolizumab) than more severe grades (2 and 3). Patients with grade 2 and 3 pneumonitis required treatment with corticosteroids, and Atezolizumab was discontinued for grade 3.

This study shows a high incidence of pneumonitis in patients receiving Atezolizumab after chemoradiation for stage III NSCLC. While age, gender, and smoking status did not appear to be significant risk factors in this cohort, the findings suggest a potential association between squamous cell carcinoma histology and increased pneumonitis risk. The small sample size limits the generalizability of these findings and prevents definitive conclusions about PDL-1 status's influence. The results emphasize the importance of close monitoring for pneumonitis in patients receiving this treatment regimen. This risk should be weighed against the potential benefits of Atezolizumab.

This retrospective study reveals a high incidence of pneumonitis in stage III NSCLC patients treated with Atezolizumab following chemoradiation. Although some trends were observed regarding histology, the small sample size limits the ability to draw firm conclusions about risk factors. Further, larger, prospective studies are needed to confirm these findings and identify reliable predictive factors for pneumonitis to better inform treatment strategies and patient management.

The main limitation of this study is its small sample size, which restricts the statistical power to identify significant associations between patient/tumor characteristics and pneumonitis risk. The retrospective nature of the study and potential for selection bias are additional limitations. Missing data on PDL-1 status further hampered the analysis of this potential risk factor.