ReviewRadiotherapy in small-cell lung cancer: Where should it go?
Introduction
Small-cell lung cancer (SCLC) represents about 12–20% of lung cancers. The histopathological differentiation between small cell and non-small cell (NSCLC) is very important as treatment strategies vary according to the pathological type. As SCLC has a high propensity for early metastatic dissemination, chemotherapy is the cornerstone treatment, but SCLC is also very sensitive to radiotherapy. Patients often have an initial bulky mediastinal presentation and have a high risk of metastatic spreading because of an elevated doubling-time [1]. Because of its unique behaviour, it has a separate staging system from NSCLC. After staging procedure, SCLC is classified as limited or extensive disease according to the Veterans Administration Lung Cancer Study Group Classification [2]. Limited disease is defined as confined to a hemithorax and the regional lymphatic nodes (mediastinum, homolateral and contralateral hilar regions, homolateral supraclavicular fossa), thus theoretically accessible to radiotherapy. Limited disease represents about a third of patients. Even if this classification has been used for many years, the International Association for the Study of Lung Cancer (IASLC) has recently published recommendations in order to use the new TNM classification also in SCLC [3]. The 7th TNM classification seems more accurate to identify patient subgroups and its use could be useful in the future.
Section snippets
Radiotherapy and chemotherapy combination
Thoracic radiotherapy (TR) was the main treatment for limited disease SCLC before the introduction of chemotherapy in the 70s. With the increasing use of chemotherapy, with response rates varying between 70% and 90%, the role of TR progressively diminished. Nevertheless, when chemotherapy was used alone, clinicians observed a high rate of local recurrence, of about 50%, which could be divided by 2 or 3 when radiotherapy was combined to chemotherapy. Several randomized trials were then performed
Thoracic radiotherapy
Even if chemotherapy is the backbone of SCLC treatment especially in extensive disease, TR has been evaluated as a consolidative therapy after chemotherapy. As thoracic control may be problematic, Jeremic et al. [67] decided to undertake a randomized study to evaluate whether thoracic radiotherapy as consolidation treatment could improve the poor results observed in SCLC extensive disease. Only patients who had an extra-thoracic complete response to 3 cycles of chemotherapy were randomized;
Conclusion
In the past ten years, progress in small-cell lung cancer comes mainly from a better integration of chemotherapy with both thoracic radiotherapy and prophylactic cranial irradiation. However there are many issues still unanswered in terms of optimal thoracic dose, optimal fractionation, optimal drug combination that need to be addressed within randomized studies. The interval between the “start of any treatment until the end of radiotherapy” (SER) which should be as short as possible, and
Conflicts of interest
None declared.
References (69)
- et al.
The IASLC Lung Cancer Staging Project: proposals regarding the relevance of TNM in the pathologic staging of small cell lung cancer in the forthcoming (seventh) edition of the TNM classification for lung cancer
J Thorac Oncol
(2009) - et al.
Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG)
Ann Oncol
(2001) - et al.
Systematic review and meta-analysis of randomised, controlled trials of the timing of chest radiotherapy in patients with limited-stage, small-cell lung cancer
Ann Oncol
(2006) - et al.
Long-term results of a phase III trial comparing once-daily radiotherapy with twice-daily radiotherapy in limited-stage small-cell lung cancer
Int J Radiat Oncol Biol Phys
(2004) - et al.
Phase I study of hypofractionated dose-escalated thoracic radiotherapy for limited-stage small-cell lung cancer
Int J Radiat Oncol Biol Phys
(2006) - et al.
Dose escalation model for limited-stage small-cell lung cancer
Radiother Oncol
(2009) - et al.
70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small-cell lung cancer: analysis of Cancer and Leukemia Group B study 39808
Int J Radiat Oncol Biol Phys
(2004) - et al.
Phase I Study of thoracic radiation dose escalation with concurrent dose escalation with concurrent chemotherapy for patients with limited small cell lung cancer: report of radiation therapy oncology group (RTOG) protocol 97-12
Int J Radiat Oncol Biol Phys
(2005) - et al.
Patterns of first failure in a phase II study of accelerated high dose thoracic radiation therapy (TRT) with concurrent chemotherapy for limited small-cell lung cancer (LSCLC): Radiation Therapy Oncology Group (RTOG) 0239
Int J Radiat Oncol Biol Phys
(2009) - et al.
Thoracic radiotherapy for limited-stage small-cell lung cancer: controversies and future developments
Clin Oncol
(2005)