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J Thorac Cardiovasc Surg 2004;127:108-113
© 2004 The American Association for Thoracic Surgery
General thoracic surgery |
a Department of Radiation Oncology, University of Pennsylvania Medical Center, Philadelphia, Pa, USA
a Hudner Oncology Center, Saint Anne's Hospital, Fall River, Mass, USA
c Department of Medical Oncology, University of Pennsylvania Medical Center, Philadelphia, Pa, USA
d Department of Thoracic Surgery, University of Pennsylvania Medical Center, Philadelphia, Pa, USA
e Department of Medical Oncology, Fox Chase Cancer Center/Temple University, Philadelphia, Pa, USA
Received for publication February 25, 2003; revisions received June 30, 2003; accepted for publication July 16, 2003.
* Address for reprints: Mitchell Machtay, MD, Hospital of the University of Pennsylvania, Department of Radiation Oncology, 2 Donner Bldg, 3400 Spruce St, Philadelphia, PA 19104, USA
machtay{at}xrt.upenn.edu
BACKGROUND: We performed this study to determine the outcomes (pathologic response, survival, local-regional control, and toxicity) in patients treated with neoadjuvant chemoradiotherapy and planned operation for stage IIIA non–small cell lung carcinoma.
METHODS: Patients treated from 1993 to 2000 with neoadjuvant chemoradiotherapy and a predetermined plan for subsequent surgical resection for stage III non–small cell lung carcinoma were analyzed. All patients underwent pretreatment evaluation at the university's Multidisciplinary Lung Cancer Center. Most patients (87%) had complete mediastinoscopy staging, and all were believed to be poor candidates for up-front operation because of bulky extent of disease. The radiotherapy program used conventional, 2-dimensionally planned treatment to 45 to 54 Gy in 1.8- to 2-Gy fraction size. Concurrent chemotherapy consisted of etoposide/cisplatin or carboplatin/paclitaxel. Study end points included resectability, pathologic response, local-regional control, survival, and toxicity. An exploratory comparison between pathologic response and long-term survival was performed. An exploratory comparison between older chemotherapy (etoposide/cisplatin) and third-generation chemotherapy (carboplatin/paclitaxel) was also performed.
RESULTS: Of 53 patients, 45 (85%) were deemed surgical candidates after induction therapy. Twenty-two (42% of the initial cohort) patients had a major pathologic response to stage 0, I, or II disease. The 5-year actuarial survival was 31%. Major pathologic response was associated with improved survival (48% vs 24%; P = .027). The overall rate of early death potentially related to therapy in this series was 9%; this mostly occurred in patients who underwent right pneumonectomy. There was no difference in efficacy or mortality between etoposide/cisplatin and radiotherapy versus carboplatin/paclitaxel and radiotherapy, although the latter regimen was associated with less grade 3 or higher acute toxicity necessitating interruption or hospitalization during neoadjuvant treatment (P = .02). In-field local control was achieved in 83% of all patients (90% of the patients who underwent resection). Brain metastases as the first site of treatment failure occurred in 23% of all patients.
CONCLUSIONS: Neoadjuvant concurrent chemoradiation delivers high resectability, major pathologic response rate, and excellent local-regional control, with encouraging long-term survival considering the patient population studied. Major pathologic response correlates with long-term survival. Neoadjuvant carboplatin/paclitaxel and radiotherapy is an appropriate framework on which to add new therapies.
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