Updated January 2014
Thoracic Irradiation for Limited Stage Small Cell Lung Cancer
Guideline: Thoracic irradiation for limited SCLC should be delivered concurrently with cisplatin/etoposide chemotherapy early (within first six weeks) in the treatment program rather than at a later time or sequentially after chemotherapy completion.
Level of Evidence: I
Integration of Chemotherapy and Radiotherapy
A randomised clinical trial performed by the National Cancer Institute of Canada showed that integration of thoracic irradiation with chemotherapy early in the treatment program (concurrently with cisplatin/etoposide at week 3) was superior to thoracic irradiation delivered at week 15 (Murray, 1993). The median survival and 5-year survival for early thoracic irradiation was 21 months and 22% versus 16 months and 13% for delayed thoracic irradiation. A number of other randomized studies have examined the effect of radiotherapy timing with results that are not entirely consistent. However, several meta-analyses have been performed that demonstrate a superior survival outcome for early thoracic irradiation for median and long-term survival (Fried, 2004, Pijls-Johannesma M). The best survival outcomes have consistently been associated with protocols that deliver cisplatin and etoposide concurrently with early thoracic irradiation (De Ruyscher). Initial concurrent chemoradiation is widely used for a number of locally advanced but non-metastatic cancers (non-small cell lung cancer, brain cancer, head and neck cancer, cancer of the cervix and cancer of the rectum. This model of therapy obeys fundamental radiobiological principles more than induction chemotherapy followed by radiotherapy.
Cyclophosphamide and anthracycline chemotherapy regimens are inferior to cisplatin and etoposide protocols in limited stage disease (Sundstrom). There is no evidence that more than four cycles of cisplatin and etoposide is associated with any survival advantage (BCCA Protocol LUSCPERT).
References:
1. Murray N, Coy P, Pater J, et al. Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. J Clin Oncol 1993;11:336-344.
2. Fried DB, Morris DE, Poole C, et al. Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol 22:4837-4845, 2004
3. Pijls-Johannesma M, De Ruysscher D, Vansteenkiske J, et al. Timing of chest radiotherapy in patients with limited stage small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials. Cancer Treat Rev 33:461-473, 2007
4. De Ruyscher D, Pijils-Johannesma M, Bentzen SM, et al : Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited-disease small-cell lung cancer. J Clin Oncol 24:1057-1063, 2006.
5. Sundstrom S, Bremnes R, Kaasa S, et al. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years’ follow-up. J Clin Oncol 20:4665-4672, 2002.
Thoracic Irradiation Dose/Fractionation in Limited SCLC
The dose/fractionation scheme traditionally employed in Canada for limited stage small cell lung cancer is 4000 cGy in 15 fractions delivered over 3 weeks. This is usually given concurrently with the first or second cycle of radiotherapy. Prompt referral to a radiation oncologist is encouraged so that arrangements may be made for early thoracic radiotherapy. Altered fractionation schemes have been investigated in limited stage small cell lung cancer. One randomized trial showed that accelerated fractionation (45Gy in three weeks with a twice daily fractionation) was superior to 45 Gy in five weeks with one fraction daily (Turrisi). It is unknown whether longer radiotherapy regimens that give a higher total dose change survival. To date, the evidence suggests that a “short-sharp” radiotherapy regimen is superior.
References:
1. Murray N, Coy P, Pater J et al. Importance of Timing for Thoracic irradiation in the Combined Modality Treatment of Limited –Stage Small-Cell Lung Cancer. Journal of Clinical Oncology 11:336-344, 1993.
2. Turrisi AT, Kim K, Blum R, Sause W, Livingston R, Komaki R, Wagner H, Aisner S, Johnson D. Twice daily compared with once-daily thoracic irradiation in limited stage small-cell lung cancer treated with concurrent cisplatin and etoposide. N Engl J Med 199;340;265-71, 1999
Thoracic Irradiation Volume in Limited SCLC
The volume to be irradiated includes the primary tumour and the affected lymph. Targeting and treating only nodal structures that measure 1 cm or larger on computed tomographic scan, clinically palpable nodes in the supraclavicular fossa and disease found by bronchoscopy constitute an appropriate target. Elective treatment of uninvolved nodes does not have a good rationale, and the risk of normal tissue exposure with toxicity of esophagitis and reduction in lung function militates strongly against expansive volumes. Early concurrent chemoradiation generally treats the pre-chemotherapy volume. When the pre-chemotherapy volume is unduly large, the treating radiation oncologist may reduce the radiation volume after a chemotherapy response. PET scans may useful to refine the radiotherapy volume.
Reference:
Murray N, Turrisi A. A review of first-line treatment for small-cell lung cancer. J Thorac Oncol. 1:270-278, 2006
