He et al. BMC Cancer 2010, 10:681 http://www.biomedcentral.com/1471-2407/10/681 Table 4 Multivariate Analysis Variable Adverse covariate Relative risk 95% CI ECOG 1 Weight loss ≥5% 2.757 2.585 1.162-6.546 1.107-6.035 95% CI indicates 95% Confidence Interval; ECOG Eastern Cooperative Oncology Group. P 0.021 0.028 end point. By further classifying SD patients, this study indicates that no optimal percentage change in tumour size associated with PFS exists in patients with NSCLC. All SD patients enjoy similar PFS and OS, which implies that they might benefit from their original treatments. This study further verifies that the current clinical norm of continuation of treatments in patients with NSCLC who have SD after two cycles of first-line platinum- based chemotherapy is the standard treatment. As noted above, this study is based solely on morpho- logical features, i.e. tumour size, which cannot reflect tumour cell viability in advanced NSCLC precisely. A study conducted by Liu-Jarin et al. also supports the notion that no correlation between tumour viability and radiographic response has been found after examination of the histological appearance of tumours after neoadju- vant therapy [28]. Since lung cancers are typically het- erogeneous, composed of both cancer cells and a host inflammatory response in various proportions. Measur- ing tumour size by anatomic imaging studies alone pro- vides only a macroscopic description of the lesion [29]. It is hard, sometimes even unlikely, to distinguish tumour from inflammatory response by a chest CT scan. For instance, a reduction in tumour cells but an increase in inflammatory component might seem equal to an increase in tumour cells but a decrease in inflam- matory component as judged from early radiographic response alone. A similar phenomenon has been noted in the evaluation of gastrointestinal stromal cell tumours (GISTs). The treatments of GISTs with chemotherapeu- tic agents rarely results in a reduction of overall tumour size, but decreases the tumour cell burden, which is undetectable by macroscopic measurement alone [30]. Histological studies of treated NSCLC have demon- strated that the percentage of residual viable tumour cells is a reliable predictor of survival, and that many tumours that exhibit little change in overall size might actually have regressed significantly [31,32]. Recent ima- ging developments based on both tumour morphology and tumour function make correct, precise, and repro- ducible measurement available. In addition, it has been proved that functional response appears relatively earlier than radiographic response [33-35]. RECIST cannot accurately reflect the change of viabi- lity of a tumour cell. This is especially true with the occurrence of targeted therapy. Many studies indicate Page 9 of 11 that after functional evaluation, some initial SD patients benefit greatly from their treatments, while some others should use an alternative therapy as early as possible. Just as Choi et al. suggest in their study that more sensi- tive criteria, a 10% decrease in size or a 15% decrease in density on contrast-enhanced CT, have been shown to be more accurate in the assessment of treatment efficacy and the prediction of survival in patients with GIST [16]. The application of PET, which can predict survival [36], to the initial SD subgroup might attain a functional response rather than an anatomical response. PET can provide some early guidance in clinical practice. Some published data indicate that the percentage [18F]fluoro- deoxyglucose uptake after one and three courses of induction chemotherapy predicts survival in stage IIIA- N2 patients [37]. Still, integration of tumour biomarkers into standard response criteria might be useful in the evaluation of NSCLC because tumour biomarkers have been proven meaningful in determining tumour biology, viability in NSCLC, and predicting outcome in patients with early stage lung cancer [38,39]. Future studies could integrate functional evaluation into the initial SD subgroup, thus might provide some early guidance on continuation/replacement of chemotherapy. It might be more important to individualize treatment for initial SD patients with advanced NSCLC as early as possible to optimize the effectiveness of the treatment. Conclusion Firstly, non-progression, i.e. PR, SD derived from the initial radiographic response after the first two courses of platinum-based chemotherapy enjoys similar PFS and OS for patients with advanced NSCLC; secondly, focused on the SD subgroup, different levels of SD (dif- ferent percentages of tumour shrinkage or increase) undergo similar PFS and OS; lastly, RECIST remains a reliable norm in assessing the effectiveness of che- motherapy for patients with advanced NSCLC and instructing clinical medication before any functional assessment has been imported into the criteria. Hope- fully, further studies will integrate functional assessment, such as contrast-enhanced CT and PET/CT, tumour biomarkers into the RECIST criteria, thus are likely to create a more reliable response criteria for advanced NSCLC in the future. Acknowledgements We thank our clinical and laboratory colleagues who have contributed to our research. Author details 1Department of Medical Oncology, The First Hospital, China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang City, China. 2Department of Respiratory Medicine, The First Hospital, China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang