J Thorac Cardiovasc Surg 2008;136:241-242
© 2008 The American Association for Thoracic Surgery
Factors predicting poor survival after resection of stage IA non–small cell lung cancer
Laura Paleari, PhDa,
Patrizia Russo, PhDa,
Alfredo Cesario, MD, PhDb,c,
Pierluigi Granone, MD, PhDb
a Lung Cancer Unit, National Cancer Research Institute, Genoa, Italy
b Surgical Pathology Unit, Catholic University, Rome, Italy
c Respiratory Unit, IRCCS "San Raffaele", Rome, Italy
To the Editor:
We have read with interest the paper by Chang and associates.1
Interestingly, we observe that the factors considered to predict poor survival after resection of stage IA non–small cell lung cancer (NSCLC) still remain tumor size, gender, age, and extent of resection.
It is true, in fact, that lung cancer staging currently rests on histopathologic and clinical criteria that have only limited power to predict relapse and survival. A major effort to improve the control of NSCLC entails the use of molecular profiling to characterize tumors and provide accurate predictions of the outcome after standard or novel treatments. Moreover, molecular profiling, as we2 already discussed in 2003, could really provide an entirely new classification system.
Recently, one study has demonstrated the potential clinical applications of gene expression profiling in a cohort of 89 patients with early-stage NSCLC in predicting the risk of disease recurrence.3 The authors evaluated the predictor in two independent groups of 25 patients from the American College of Surgeons Oncology Group Z0030 study and 84 patients from the Cancer and Leukemia Group B 9761 study. The overall predictive accuracy was 72% and 79%, respectively. The predictor also identified a subgroup of patients with stage IA disease who were at high risk for recurrence and who might be best treated by adjuvant chemotherapy. Additionally, an 11-gene expression signature associated with "stem cell-ness" was found to divide patients with different cancers, including NSCLC, into good- and poor-prognosis groups; however, this stem cell–associated signature has not been validated or further studied in NSCLC.4 On a pragmatic basis, a rigorous prospective approach, using training and testing cohorts, to study molecular prognostic markers could improve chances of identifying true molecular prognostic markers that may be reliably applied to clinical practice. Potential research goals may include the following (1): identify molecular tissue, blood, and plasma markers (ie, gene expression profile, genetic polymorphism, genetic/epigenetic alterations, plasma proteomic) predictive of survival, recurrence, and metastasis development in patients with NSCLC; (2) establish characteristics of precursor lesions and the field of cancerization phenomenon in NSCLC pathogenesis by smoking status, gender, and ethnic background; (3) establish molecular markers to discover occult micrometastasis in lymph nodes (sentinel lymph node); (4) evaluate the presence of "stem-cancer cells"; (5) identify molecular tissue and blood markers to predict response to adjuvant chemotherapy; (6) identify molecular markers predictive of response to chemotherapeutic or targeted therapeutic agents at time of recurrence. Therefore, development of a tissue and blood (serum, plasma, and circulating cells) bank with specimens obtained in clinical trials, including detailed prospective collected clinical data, is of the utmost importance. This new phase of target profiling and agent-specific profiling will probably require an algorithm that would include genomic, proteomic, clinical, and imaging factors.
Patients with early-stage NSCLC will be assigned to particular drugs on the basis of the molecular characteristics of their tumors. Then the development of drugs for the treatment of NSCLC will be focused on personalized therapy.
Figure 1 outlines a possible application of molecular biology to refine the assessment of risk and guide the use of adjuvant chemotherapy in stage IA NSCLC.
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Figure 1. Application of molecular biology to refine the assessment of risk and guide the use of adjuvant chemotherapy in stage IA non–small cell lung cancer (NSCLC).
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References
- Chang MY, Mentzer SJ, Colson YL, Linden PA, Jaklitsch MT, Lipsitz SR, et al. Factors predicting poor survival after resection of stage IA non–small cell lung cancer. J Thorac Cardiovasc Surg 2007;134:850-856.[Abstract/Free Full Text]
- Cesario A, Galletta D, Russo P, Margaritora S, Granone P. The role of the surgeon in translational research. Lancet 2003;362:1082.[Medline]
- Potti A, Mukherjee S, Petersen R, Dressman HK, Bild A, Koontz J, et al. A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. N Engl J Med 2006;355:570-580.[Medline]
- Glinsky GV, Berezovska O, Glinskii AB. Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest 2005;115:1503-1521.[Medline]
