Thoracic radiotherapy improves survival in small-cell lung cancer patients

1. The addition of thoracic radiotherapy in patients receiving prophylactic cranial irradiation and chemotherapy was shown to significantly increase overall survival at two years in patients with extensive-stage small cell lung cancer (ES-SCLC).

2. Disease progression was less likely in patients receiving thoracic radiotherapy in addition to prophylactic cranial irradiation and chemotherapy, than in patients receiving prophylactic cranial irradiation and chemotherapy alone.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Approximately 13% of all lung cancer is small-cell lung cancer, which often presents at an advanced stage. The prognosis is poor and few adjunct treatments are available, with chemotherapy being the mainstay of treatment. While prophylactic cranial irradiation has shown to be effective for prevention of brain metastasis, treating intrathoracic disease remains a challenge. This study investigated the use of thoracic radiotherapy for treatment of intrathoracic disease in patients receiving prophylactic intracranial irradiation who had shown a response to chemotherapy. In addition to prophylactic cranial irradiation and chemotherapy, patients were randomly assigned to either receive thoracic radiotherapy (experimental group) or no thoracic radiotherapy (control group).

The study found that the addition of thoracic radiotherapy did not significantly improve one-year overall survival, but that two-year overall survival was significantly improved and progression-free survival greatly increased. This finding implicates the consideration of intrathoracic radiotherapy in addition to prophylactic intracranial irradiation for patients with ES-SCLC who respond to chemotherapy. This study’s strength comes from the effective randomization and high participant compliance rate (95%). A limitation of this study is the lack of patient-reported outcomes related to quality of life, which may actually encompass the patient experience more effectively than the treatment does. Quality of life in patients with advanced stage cancers is always an important consideration.

This study was funded by Dutch Cancer Society (CKTO), Dutch Lung Cancer Research Group, Cancer Research UK, Manchester Academic Health Science Centre Trials Coordination Unit, and the UK National Cancer Research Network.

Click to read the study, published today in The Lancet

Relevant Reading: Clinical Outcomes of Extensive Stage Small Cell Lung Carcinoma Patients Treated With Consolidative Thoracic Radiotherapy

In-Depth [randomized controlled trial]: This phase 3 randomized controlled study was conducted across 42 hospitals in the Netherlands, Belgium, the United Kingdom, and Norway. Participants were age 18+ with a WHO performance status of 0-2 who had extensive-stage SCLC that had responded to chemotherapy. The experimental group, 247 patients, received thoracic radiotherapy in addition to intracranial irradiation and chemotherapy. The control group, 248 patients, received no thoracic radiotherapy in addition to intracranial irradiation and chemotherapy. Overall survival at one year was the primary endpoint, and median overall survival and overall survival at two years were also analyzed.

Overall survival at one year was 33% (95% confidence interval, CI, 27-39) in the experimental group and 28% (95% CI 22-34) in the control group. This difference was not significant (hazard ratio, HR, 0.84, 95% CI 0.69–1.01, p=0.066). Median overall survival was found to be eight months in both groups. Overall survival at two years was 13% (95% CI 9-19) in the experimental group and 3% (95% CI 2-8) in the control group (p=0.004). The experimental group also showed less likely disease progression than the control group (HR 0.73, 95% CI 0.61-0.87, p=0.001).

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