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CHICAGO - New data suggest that microscopic vascular invasion may be a more powerful prognosticator in early lung cancer than are the tumor size-based categories suggested in the new TNM staging system.
Italian researchers used histologic and immunohistochemical techniques to identify microscopic vascular invasion (MVI), or the presence of neoplastic structures inside the lumen of a vessel, in one-third (154) of 512 patients with resected, pathologically staged T1a to T3 node-negative non-small cell lung cancer (NSCLC). The 2009 edition of the tumor, node, metastasis (TNM) staging system for lung tumors was used.
MVI was significantly correlated with the presence of tumor-infiltrating lymphocytes (odds ratio 1.65, P value = .03), adenocarcinoma histology (OR 1.32, P = .003), and increased tumor size (OR 1.13, P = .009).
Five-year overall survival was significantly lower for patients with MVI at 50% vs. those without MVI at 66% (P = .001), Dr. Enrico Ruffini said at the Chicago Multidisciplinary Symposium in Thoracic Oncology.
The difference in survival remained significant even in those with squamous cell carcinoma (45% vs. 61%, P = .05), although it was more pronounced in those with adenocarcinoma (56% vs. 70%, P = .03).
"Microscopic vascular invasion is a significant independent negative prognostic factor," he said.
When patients with pT1a-T2b tumors were stratified by T-size category, the presence of MVI resulted in a one-category upstaging for each T category, said Dr. Ruffini of the division of thoracic surgery at the University of Torino (Italy). For example, T1a patients with MVI had a prognosis similar to that of patients with T1b tumors without MVI. The number of T3 cases was too small to stratify.
T size was prognostic of survival in the MVI-negative patients (P = .03) but was not a statistically significant factor in MVI-positive patients (P = .9), indicating that MVI is indeed a more powerful prognosticator, he said.
The 2009 TNM stresses the importance of tumor size as a major prognostic factor, but no TNM edition has so far included MVI as a major determinant in the staging of NSCLC.
In a multivariate survival analysis that included age, sex, histology, grading, T-size determinant, MVI, perineural invasion, and tumor-infiltrating lymphocytes, MVI was a stronger prognostic indicator (hazard ratio 1.43, P = .02) than T-size determinant (HR 1.06, P = .06), Dr. Ruffini said.
"The use of adjuvant chemotherapy in NSCLC patients with MVI may be considered," he said.
Invited discussant Dr. Mark Socinski pointed out that 88% of patients in the analysis had 5 cm or smaller tumors, a category of patients in which the role of adjuvant therapy has been discouraged. He highlighted the recent LACE meta-analysis of 4,584 NSCLC patients in five cisplatin-based adjuvant chemotherapy trials that showed an overall significant survival benefit of 4% at 5 years, but also a potentially negative effect in resected stage 1A (Ann. Oncol. 2010 Oct;21 Suppl. 7:vii196-vii198).
"We need to make sure [MVI] is easily reproducible amongst pathologists, and we also clearly need to demonstrate that adjuvant therapy can overcome the biologic impact of this histopathologic finding," said Dr. Socinski of the Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill.
Dr. Ruffini acknowledged that bias could have been introduced into the study through its retrospective design, use of overall survival rather than disease-free survival as an outcome measure, and the long study period of January 1998 to August 2008. Prospective validation of MVI is underway using the prospective International Association for the Study of Lung Cancer database, he said.
The median tumor size among the 512 patients was 3.4 cm, with 164 classified as having T1a (less than 2 cm) tumors, 123 T1b (2-3 cm), 164 T2a (3-5 cm), 50 T2b (5-7 cm), and 11 T3 (greater than 7 cm) tumors.
The researchers and Dr. Socinski disclosed no relevant conflicts.
Subtle histologic markers have long been championed as a potential means to this ends, but historically gain little traction because essentially all are trumped by the presence of either metastic disease or regional lymph node involvement as important risks for recurrence. Consequently, the use of more sophisticated, but perhaps less reproduceable, pathologic markers is retricted to node-negative cancers, where T (of TNM) descriptors are important. This represents only about one-quarter of all lung cancers detected.
The authors have proposed microscopic vascular invasion (MVI) as an important factor that might be a reasonable addition to the T aspect of the new staging system. Their data demonstrate that MVI (found in a relatively small cohort of all node-negative patients in their study) appears to be an important risk for mortality. However, the road to the perfect staging system is paved with new histopathologic markers, and few are adopted because another one soon emerges and it is difficult for pathologists to keep up.
I think that molecular and radiologic characterization will eventually supplant all such subjective histopathologic markers and, within the next few years, will make the microscope something we'll be telling our grandkids about.
Subtle histologic markers have long been championed as a potential means to this ends, but historically gain little traction because essentially all are trumped by the presence of either metastic disease or regional lymph node involvement as important risks for recurrence. Consequently, the use of more sophisticated, but perhaps less reproduceable, pathologic markers is retricted to node-negative cancers, where T (of TNM) descriptors are important. This represents only about one-quarter of all lung cancers detected.
The authors have proposed microscopic vascular invasion (MVI) as an important factor that might be a reasonable addition to the T aspect of the new staging system. Their data demonstrate that MVI (found in a relatively small cohort of all node-negative patients in their study) appears to be an important risk for mortality. However, the road to the perfect staging system is paved with new histopathologic markers, and few are adopted because another one soon emerges and it is difficult for pathologists to keep up.
I think that molecular and radiologic characterization will eventually supplant all such subjective histopathologic markers and, within the next few years, will make the microscope something we'll be telling our grandkids about.
Subtle histologic markers have long been championed as a potential means to this ends, but historically gain little traction because essentially all are trumped by the presence of either metastic disease or regional lymph node involvement as important risks for recurrence. Consequently, the use of more sophisticated, but perhaps less reproduceable, pathologic markers is retricted to node-negative cancers, where T (of TNM) descriptors are important. This represents only about one-quarter of all lung cancers detected.
The authors have proposed microscopic vascular invasion (MVI) as an important factor that might be a reasonable addition to the T aspect of the new staging system. Their data demonstrate that MVI (found in a relatively small cohort of all node-negative patients in their study) appears to be an important risk for mortality. However, the road to the perfect staging system is paved with new histopathologic markers, and few are adopted because another one soon emerges and it is difficult for pathologists to keep up.
I think that molecular and radiologic characterization will eventually supplant all such subjective histopathologic markers and, within the next few years, will make the microscope something we'll be telling our grandkids about.
CHICAGO - New data suggest that microscopic vascular invasion may be a more powerful prognosticator in early lung cancer than are the tumor size-based categories suggested in the new TNM staging system.
Italian researchers used histologic and immunohistochemical techniques to identify microscopic vascular invasion (MVI), or the presence of neoplastic structures inside the lumen of a vessel, in one-third (154) of 512 patients with resected, pathologically staged T1a to T3 node-negative non-small cell lung cancer (NSCLC). The 2009 edition of the tumor, node, metastasis (TNM) staging system for lung tumors was used.
MVI was significantly correlated with the presence of tumor-infiltrating lymphocytes (odds ratio 1.65, P value = .03), adenocarcinoma histology (OR 1.32, P = .003), and increased tumor size (OR 1.13, P = .009).
Five-year overall survival was significantly lower for patients with MVI at 50% vs. those without MVI at 66% (P = .001), Dr. Enrico Ruffini said at the Chicago Multidisciplinary Symposium in Thoracic Oncology.
The difference in survival remained significant even in those with squamous cell carcinoma (45% vs. 61%, P = .05), although it was more pronounced in those with adenocarcinoma (56% vs. 70%, P = .03).
"Microscopic vascular invasion is a significant independent negative prognostic factor," he said.
When patients with pT1a-T2b tumors were stratified by T-size category, the presence of MVI resulted in a one-category upstaging for each T category, said Dr. Ruffini of the division of thoracic surgery at the University of Torino (Italy). For example, T1a patients with MVI had a prognosis similar to that of patients with T1b tumors without MVI. The number of T3 cases was too small to stratify.
T size was prognostic of survival in the MVI-negative patients (P = .03) but was not a statistically significant factor in MVI-positive patients (P = .9), indicating that MVI is indeed a more powerful prognosticator, he said.
The 2009 TNM stresses the importance of tumor size as a major prognostic factor, but no TNM edition has so far included MVI as a major determinant in the staging of NSCLC.
In a multivariate survival analysis that included age, sex, histology, grading, T-size determinant, MVI, perineural invasion, and tumor-infiltrating lymphocytes, MVI was a stronger prognostic indicator (hazard ratio 1.43, P = .02) than T-size determinant (HR 1.06, P = .06), Dr. Ruffini said.
"The use of adjuvant chemotherapy in NSCLC patients with MVI may be considered," he said.
Invited discussant Dr. Mark Socinski pointed out that 88% of patients in the analysis had 5 cm or smaller tumors, a category of patients in which the role of adjuvant therapy has been discouraged. He highlighted the recent LACE meta-analysis of 4,584 NSCLC patients in five cisplatin-based adjuvant chemotherapy trials that showed an overall significant survival benefit of 4% at 5 years, but also a potentially negative effect in resected stage 1A (Ann. Oncol. 2010 Oct;21 Suppl. 7:vii196-vii198).
"We need to make sure [MVI] is easily reproducible amongst pathologists, and we also clearly need to demonstrate that adjuvant therapy can overcome the biologic impact of this histopathologic finding," said Dr. Socinski of the Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill.
Dr. Ruffini acknowledged that bias could have been introduced into the study through its retrospective design, use of overall survival rather than disease-free survival as an outcome measure, and the long study period of January 1998 to August 2008. Prospective validation of MVI is underway using the prospective International Association for the Study of Lung Cancer database, he said.
The median tumor size among the 512 patients was 3.4 cm, with 164 classified as having T1a (less than 2 cm) tumors, 123 T1b (2-3 cm), 164 T2a (3-5 cm), 50 T2b (5-7 cm), and 11 T3 (greater than 7 cm) tumors.
The researchers and Dr. Socinski disclosed no relevant conflicts.
CHICAGO - New data suggest that microscopic vascular invasion may be a more powerful prognosticator in early lung cancer than are the tumor size-based categories suggested in the new TNM staging system.
Italian researchers used histologic and immunohistochemical techniques to identify microscopic vascular invasion (MVI), or the presence of neoplastic structures inside the lumen of a vessel, in one-third (154) of 512 patients with resected, pathologically staged T1a to T3 node-negative non-small cell lung cancer (NSCLC). The 2009 edition of the tumor, node, metastasis (TNM) staging system for lung tumors was used.
MVI was significantly correlated with the presence of tumor-infiltrating lymphocytes (odds ratio 1.65, P value = .03), adenocarcinoma histology (OR 1.32, P = .003), and increased tumor size (OR 1.13, P = .009).
Five-year overall survival was significantly lower for patients with MVI at 50% vs. those without MVI at 66% (P = .001), Dr. Enrico Ruffini said at the Chicago Multidisciplinary Symposium in Thoracic Oncology.
The difference in survival remained significant even in those with squamous cell carcinoma (45% vs. 61%, P = .05), although it was more pronounced in those with adenocarcinoma (56% vs. 70%, P = .03).
"Microscopic vascular invasion is a significant independent negative prognostic factor," he said.
When patients with pT1a-T2b tumors were stratified by T-size category, the presence of MVI resulted in a one-category upstaging for each T category, said Dr. Ruffini of the division of thoracic surgery at the University of Torino (Italy). For example, T1a patients with MVI had a prognosis similar to that of patients with T1b tumors without MVI. The number of T3 cases was too small to stratify.
T size was prognostic of survival in the MVI-negative patients (P = .03) but was not a statistically significant factor in MVI-positive patients (P = .9), indicating that MVI is indeed a more powerful prognosticator, he said.
The 2009 TNM stresses the importance of tumor size as a major prognostic factor, but no TNM edition has so far included MVI as a major determinant in the staging of NSCLC.
In a multivariate survival analysis that included age, sex, histology, grading, T-size determinant, MVI, perineural invasion, and tumor-infiltrating lymphocytes, MVI was a stronger prognostic indicator (hazard ratio 1.43, P = .02) than T-size determinant (HR 1.06, P = .06), Dr. Ruffini said.
"The use of adjuvant chemotherapy in NSCLC patients with MVI may be considered," he said.
Invited discussant Dr. Mark Socinski pointed out that 88% of patients in the analysis had 5 cm or smaller tumors, a category of patients in which the role of adjuvant therapy has been discouraged. He highlighted the recent LACE meta-analysis of 4,584 NSCLC patients in five cisplatin-based adjuvant chemotherapy trials that showed an overall significant survival benefit of 4% at 5 years, but also a potentially negative effect in resected stage 1A (Ann. Oncol. 2010 Oct;21 Suppl. 7:vii196-vii198).
"We need to make sure [MVI] is easily reproducible amongst pathologists, and we also clearly need to demonstrate that adjuvant therapy can overcome the biologic impact of this histopathologic finding," said Dr. Socinski of the Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill.
Dr. Ruffini acknowledged that bias could have been introduced into the study through its retrospective design, use of overall survival rather than disease-free survival as an outcome measure, and the long study period of January 1998 to August 2008. Prospective validation of MVI is underway using the prospective International Association for the Study of Lung Cancer database, he said.
The median tumor size among the 512 patients was 3.4 cm, with 164 classified as having T1a (less than 2 cm) tumors, 123 T1b (2-3 cm), 164 T2a (3-5 cm), 50 T2b (5-7 cm), and 11 T3 (greater than 7 cm) tumors.
The researchers and Dr. Socinski disclosed no relevant conflicts.