Small Cell Cancer of the Lung

Thoracic Radiotherapy (from the NCCN)

The addition of thoracic radiotherapy has improved survival for patients with limited-stage disease. Meta-analyses that included more than 2000 patients show that thoracic radiation for limited stage disease causes a 25% to 30% reduction in local failure and a corresponding 5% to 7% improvement in 2-year survival. However, achieving local control using conventional chemoradiotherapy for patients with limited-stage SCLC remains a challenge.

The administration of thoracic radiotherapy requires the assessment of several factors, including the timing of chemotherapy and radiotherapy (concurrent versus sequential versus alternating therapy), timing of radiotherapy (early versus late), volume of the radiation port (original tumor volume versus shrinking field as the tumor responds), dose of radiation, and fractionation of radiotherapy.

A randomized trial by the Japanese Cooperative Oncology Group assessed sequential versus concurrent thoracic radiotherapy combined with EP for patients with limited-stage disease, and reported that patients treated with concurrent radiotherapy lived longer than those treated with sequential radiotherapy. Another randomized phase III trial by the National Cancer Institute of Canada compared radiotherapy beginning with either cycle 2 or cycle 6 of chemotherapy, and demonstrated that early radiotherapy was associated with improved local and systemic control and longer survival.

A systematic review on the timing of thoracic radiotherapy in limited-stage SCLC determined that early concurrent radiotherapy results in a small, but significant, improvement in overall survival when compared to late concurrent or sequential radiotherapy. Based on a phase II study by Turrisi et al, the Eastern Cooperative Oncology Group/Radiation Therapy Oncology Group (ECOG/RTOG) compared once a day to twice a day radiotherapy with EP. In this trial, 412 patients with limited-stage SCLC were treated with concurrent chemoradiotherapy using a total dose of 45 Gy delivered either twice a day over 3 weeks or once a day over 5 weeks. The twice- daily schedule produced a survival advantage along with a higher incidence of grade 3-4 esophagitis. Median survival was 23 versus 19 months ( = .04), and 5-year survival was 26% versus 16% in the twice-daily and once-daily radiotherapy arms, respectively. A caveat to these encouraging long-term survival results is that twice-daily fractionation is technically challenging for patients with bilateral mediastinal adenopathy. In addition, the once-a-day therapy was not delivered at its maximum tolerated dose, so it remains unclear if hyperfractionation is superior to once daily chest radiotherapy given to a biologically equivalent dose. Another randomized phase III trial demonstrated no survival difference between once-a-day thoracic radiotherapy to 50.4 Gy with concurrent EP and a split-course of twice-a-day thoracic radiotherapy to 48 Gy with concurrent EP. However, split-course radiotherapy may be less efficacious because of interval tumor regrowth between courses. Overall, patients selected for combined modality treatment that incorporates twice-a-day radiotherapy must have an excellent PS and good baseline pulmonary function.

For limited-stage disease, the NCCN guidelines recommend that radiation should be delivered concurrently with chemotherapy and should start with the first or second cycle at a dose of either 1.5 Gy twice daily to a total dose of 45 Gy, or 1.8 Gy/day to at least 50 Gy. The radiation target volumes should be defined on the CT scan obtained at the time of radiotherapy planning. However, the pre-chemotherapy CT scan should be reviewed to include the originally involved lymph node regions in the treatment fields.