Meta-analysis of the influence of surgical margin and adjuvant radiotherapy on local recurrence after resection of sporadic desmoid-type fibromatosis.

BACKGROUND: Extra-abdominal desmoid-type fibromatosis (DF) is a rare, locally aggressive neoplasm that is usually managed conservatively. When treatment is indicated, it typically involves surgical resection, possibly with adjuvant radiotherapy. The indications for postoperative radiotherapy and its effectiveness are unclear. The objective of this study was to estimate the effect of surgical resection margins and adjuvant radiotherapy on rates of recurrence of DF. METHODS: Literature published between 1999 and 2015 was extracted from MEDLINE, Embase, Cochrane Central Registry of Trials, Web of Science and Google Scholar. Recurrence rate was analysed by meta-analysis and compared between subgroups. RESULTS: Sixteen reports were included, consisting of a total of 1295 patients with DF. In patients treated by surgical resection alone, the risk of local recurrence was almost twofold higher for those with microscopically positive resection margins (risk ratio (RR) 1·78, 95 per cent c.i. 1·40 to 2·26). Adjuvant radiotherapy after surgery with negative margins had no detectable benefit on recurrence. In contrast, after incomplete surgical resection, adjuvant radiotherapy improved recurrence rates both in patients with primary tumours (RR 1·54, 1·05 to 2·27) and in those with recurrent DF (RR 1·60, 1·12 to 2·28). CONCLUSION: DF resected with microscopically positive margins has a higher risk of recurrence. Adjuvant radiotherapy appears to reduce the risk of recurrence after incomplete surgical resection, particularly in patients with recurrent tumours.

Pathologic fracture a poor prognostic factor in osteosarcoma: Misleading conclusions from meta-analyses?

AIM: Recently published meta-analyses have concluded that pathologic fracture is a negative prognostic factor in osteosarcoma. But several confounding variables were not accounted for in the index studies, thereby compromising internal validity. METHODS: A multivariable survival analysis of a retrospective cohort of 131 patients with conventional, high-grade osteosarcoma of the extremity long bones treated with neoadjuvant chemotherapy and surgical resection was performed. RESULTS: There were no significant differences in clinicopathologic variables between the 21 patients who suffered pathologic fracture and the 110 patients who did not in standard bivariable statistical tests. Hazard ratios for decreased overall and disease-free survival of patients with pathologic fracture failed to reach statistical significance in univariable Cox proportional hazard regression. Furthermore, pathologic fracture did not significantly affect patient outcome (hazard ratio for overall survival, 1.15 [95% CI 0.56-2.38], P = 0.71 or disease-free survival, 1.01 [95% CI 0.53-1.91], P = 0.98) after controlling for confounding factors not accounted for in prior meta-analyses, such as tumor size, chemotherapy response, and proximal tumor location. CONCLUSIONS: Pathologic fracture is not a significant prognostic factor for extremity osteosarcoma after controlling for other established prognostic factors. Although a useful statistical method, meta-analysis can generate false conclusions if important confounding factors are ignored. Analysis of individual patient data, which would require collaboration among different groups, would circumvent this limitation of meta-analysis.

Immunohistochemical analysis of receptor tyrosine kinase signal transduction activity in chordoma.

AIMS: Currently, there are no effective chemotherapeutic protocols for chordoma. Reports of receptor tyrosine kinase (RTK) expression in chordoma suggest that these tumours may respond to kinase inhibitor therapy. However, RTK signalling activity has not been extensively investigated in chordoma. METHODS: A tissue microarray containing 21 cases of chordoma was analysed for expression of a number of proteins involved in signal transduction from RTKs by immunohistochemistry. RESULTS: Platelet-derived growth factor receptor-beta, epidermal growth factor receptor (EGFR), KIT and HER2 were detected in 100%, 67%, 33% and 0% of cases, respectively. Platelet-derived growth factor receptor-beta staining was of moderate-to-strong intensity in 20 of 21 cases. In contrast, KIT immunoreactivity was weak and focal in each of the seven positive cases. Total EGFR staining was variable; weak staining for phosphorylated EGFR was detected in nine cases. Phosphorylated isoforms of p44/42 mitogen-activated protein kinase, Akt and STAT3, indicative of tyrosine kinase activity, were detected in 86%, 76% and 67% of cases, respectively. CONCLUSIONS: Chordomas commonly express RTKs and activated signal transduction molecules. Although there were no statistically significant correlations between the expression of any of the markers studied and disease-free survival or tumour location, the results nonetheless indicate that chordomas may respond to RTK inhibitors or modulators of other downstream signalling molecules.