| Objective: Three dimensional conformal radiotherapy (3DCRT) is a mode of precision radiation therapy which offers the prospect of improved local control of locally advanced non-small cell lung cancer (NSCLC). The determination of the clinical target volume (CTV) is probably one of the most difficult challenges for radiotherapists. They must define the limits of the CTV based exclusively on their own experience, as none of the available imaging techniques allows to detect microscopic extension (ME) directly. To define the CTV according to the degree of local microscopic extension is one of the most important steps of the three dimensional conformal radiotherapy. In this study, we tried to quantify this ME in non-small-cell lung cancer with pathological method.Methods: From February 2003 to September 2003, surgical specimens were obtained from 79 cases with NSCLC who had undergone resection of the primary tumor with lymph node dissection at the Forth Hospital of HeBei Medical University. 69 specimens were selected, 30 were adenocarcinoma (ADC) and 39 specimens were squamous cell carcinoma (SCC). The surgical resection specimens for which the border between tumor and adjacent lung parenchyma were examined on routine sections. Defining the border of tumors with the naked eye, outlined it with a marker pen. The value of the local ME outside of this border was measured with an eyepiece micrometer by light microscopy and the maximum value of each slide was recorded. Pathologic type, histological grade, vascular extension of tumors and other factors also were studied. The mean length of ME in different clinicopathological subgroups were analyzed statistically.Results: A total of 167 slides were studied, corresponding to 64 slides for adenocarcinoma (38.3%) and 103 slides for squamous cell carcinoma (61.7%). (1) The value of ME was 1.95±1.38mm for ADC, significantly greater than that of SCC, which was 1.03±1.42mm (t=4.129, p=0.000<0.05). To take into account 95% of the ME, a margin of 4.21 mm and 3.32 mm must be chosen for ADC and SCC, respectively. (2) For both ADC and SCC, tumors with vascular extension had greater microscopic extension than those which presented exclusively local extension (2.70 vs 1.79 mm, t=3.216, p=0.003 and 2.02 vs 0.76mm, t=3.319, p=0.003). (3) For SCC, we found that ME was greater for the tumors with spiculated apperance than those which presented nodular apperance (1.65 vs 0.82 mm, p=0.028), the difference was similar but not statistically significant for ADC (t=0.325, p=0.746>0.05). (4) The value of ME in ADC of two groups (maximum diameter ≤3cm and ＞3cm) were 1.26±1.46mm and 2.68±0.80mm respectively, there was statistical significance between the two groups (t=-4.874, p=0.000<0.001). The same two groups of SCC of which ME were 1.77±1.25mm and 0.88±1.41mm respectively also had statistical significance (t=2.442, p=0.016<0.05). (5) In the same pathological types, either ADC or SCC, no significant difference was found between the ME of the subgroups of tumor site (t=-0.258, p=0.797>0.05; t=-0.906, p=0.370>0.05), histological grade (t=0.681, p=0.499>0.05; t=-0.707, p=0.481>0.05). (6)The differences of ME between different T-stage have statistical significance according to ANONA in the same pathological types (FADC=3.780, pADC=0.028<0.05; FSCC=3.227, pSCC=0.044<0.05). (7) According to ANONA, significant differences were found between different N-stage for SCC (F=4.343, p=0.006<0.05), but not for ADC (F=1.679, p=0.195>.05).Conclusions: The difference of the ME between ADC and SCC have statistical significance. To cover 95% of the ME, a margin of 4.21mm and 3.32mm must be chosen for ADC and SCC respectively at least. In our study, in the same pathological types, factors such as vascular extension, tumor size and T-stage significantly correlated with ME, but no significant difference was found between the ME of the subgroups of tumor site, histological grade. Significant differences were found between different N-stage for SCC but not for ADC.
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