Ann Thorac Surg 2008;86:910-911. doi:10.1016/j.athoracsur.2008.07.008
© 2008 The Society of Thoracic Surgeons
Original Articles: General Thoracic
Invited Commentary
Ken Kodama, MD
Department of Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511 Japan
(Email: kodama-ke{at}mc.pref.osaka.jp).
Although several trials of induction chemoradiotherapy followed by surgery have been reported to date, the role of tri-modality therapy in stage III nonsmall cell lung cancer (NSCLC) is highly controversial. Edelman and colleagues [1] reported the results of a phase I–II trial of maximally local and systemic disease control for biopsy proven stage IIIA or IIIB NSCLC. The main objective was to determine the ability to intensify tri-modality therapy using concurrent 69.6 Gy of hyperfractionated radiotherapy and more aggressive consolidative chemotherapy. As a result, the median survival time (MST) was 55.8 months for 28 patients with mediastinal clearance who underwent resection. The MST is favorable compared with other reports. However, it is controversial whether patients with a tumor originating from the lower lobe requiring a larger radiation field, including the primary tumor, pulmonary hilum, and mediastinum should be included as candidates for this type of tri-modality therapy.
The optimal treatment of locally advanced NSCLC should be based on accurate staging of the mediastinal lymph nodes both at diagnosis and after induction chemoradiotherapy. The re-staging procedure allows for the selection of subgroups of patients in whom surgery seems to improve survival. Thus, it is important to note that 15 patients with persistent mediastinal disease, despite the successful completion of induction therapy, were excluded from the candidates for radical surgery in the present study. Previous trials identified mediastinal lymph node clearance and complete resection by lobectomy (but not pneumonectomy) as two significant prognostic factors for improving the overall survival.
A pathologic complete response was noted in 28% (8 of 29) of the surgical patients or 17% (8 of 47) of the entire study population in the present study. Approximately 9 to 10 months are required from the start of induction chemoradiotherapy through to surgery via consolidative chemotherapy followed by prophylactic cranial irradiation (PCI). Sites of failure in 29 patients were equally distributed locally or systemically. These results may suggest that a small population of cancer cells arrested in the G0 phase of the cell cycle (ie, cancer stem cells may be inherently resistant to the current therapeutic approaches, even if aggressive consolidative chemotherapy and PCI are administered). The development of a method to kill cancer stem cells as an alternative may constitute a significant future field of study. The elimination of cancer stem cells may result in improved therapeutic outcomes for patients with advanced NSCLC. Also, when we consider the cost–benefit ratio and improved survival, future studies should address methods of customizing drugs based on the expression levels of molecular markers.
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- Edelman MJ, Suntharalingam M, Burrows W, et al. Phase I/II trial of hyperfractionated radiation and chemotherapy followed by surgery in stage III lung cancer Ann Thorac Surg 2008;86:903-911.[Abstract/Free Full Text]
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Phase I/II Trial of Hyperfractionated Radiation and Chemotherapy Followed by Surgery in Stage III Lung Cancer
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