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Ann Thorac Surg 2003;76:187-193
© 2003 The Society of Thoracic Surgeons
a Thoracic Oncology Program, Comprehensive Cancer Center, Duke University Medical Center, Durham, North Carolina, USA
* Address reprint requests to Dr Harpole, DUMC Box 3627, Durham, NC 27710, USA.
e-mail: harpo002{at}surgerytrials.duke.edu
Presented at the Forty-eighth Annual Meeting of the Southern Thoracic Surgical Association, San Antonio, TX, Nov 8–10, 2001.
BACKGROUND: The long-term survival of patients with stage III non–small cell lung cancer treated with a combination of chemotherapy and radiation is 10% to 20%. Survival could potentially be increased and toxicity limited if one could identify patients most likely to respond to a particular treatment regimen. This project prospectively evaluated a panel of potential immunohistochemical markers of chemoresistance in a population of patients with pathology-confirmed stage III non–small cell lung cancer in order to determine the prognostic value of each marker in relation to response to chemotherapy or survival.
METHODS: Immunohistochemical staining was performed on histologically positive mediastinal nodal specimens obtained from 59 patients (mean age, 62 years; range, 41 to 79 years) without evidence of distant metastatic disease treated with navelbine-based chemotherapy and external beam radiation therapy between 1996 and 2001. Included were markers for apoptosis (p53, bcl-2), drug efflux/degradation (MDR, GST-
), growth factors (EGFr, Her2-neu), and mismatch repair (hMLH1, hMSH2). After chemotherapy, patients underwent radiologic evaluation for response measured by standard criteria.
RESULTS: After a median 41 months of follow-up (range, 17 to 55 months), 43 patients had recurrent disease and 38 of these patients were dead of cancer (median cancer-free survival of 10 months and overall survival of 18 months). Patients who demonstrated a complete or partial response (n = 38) had a significantly improved survival (p = 0.002) compared with those with stable or progressive cancer (n = 21). Multivariable Cox step-wise regression analysis of marker expression associated overexpression of p53 and low expression of hMSH2 with poor treatment response and cancer death.
CONCLUSIONS: These preliminary data suggest that marker expression may allow the separation of patients into low- and high-risk groups with respect to survival after combined navelbine-based chemotherapy and XRT. This could represent a novel method of selecting patients for a particular treatment regimen if these data are reproduced in a larger prospective trial.
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