A Reassessment of the Barrier Effect of the Physis against Metaphyseal Osteosarcoma: A Comprehensive Pathological Study with Its Radiological and Clinical Follow-Up Correlations

Abstract

Osteosarcoma is a primary malignant bone tumor usually arising at the metaphysis of long bones, particularly around the knee. The physis has been regarded as a barrier capable of blocking tumor extension, thus allowing it to preserve their epiphysis and therefore improve functional results. With the objective of clarifying how effective the physis is as a barrier to tumor spread, a large series of skeletally immature patients with osteosarcoma were reviewed. From 452 metaphyseal osteosarcomas a selection of 282 cases in which the tumor was close or crossing the physis were carried out. This sub-sample was split into two groups according to the surgical treatment (epiphyseal preservation or not). The specimens obtained by resection were studied, and the physeal and metaphyseal areas were studied by multiple sections. Immunostaining against VEGF of physis was obtained in selected cases. In about half of the patients affected by metaphyseal malignant bone tumors, the growth plate and epiphysis were not compromised by the tumor. Three sequential invasive growth patterns of an osteosarcoma in its relationship with the physis could be distinguished. An intense angiogenesis and osteoclastic reaction could be observed in the growth plate in the free zone between the tumor and the physis. The local recurrence incidence was lower in the epiphyseal preservation treated patients than it was in the conventional treatment (8% vs. 12%). Most local recurrences appeared in the first 2 years. The overall survival of patients treated with epiphyseal preservation was better than that of the patients treated without preserving the epiphysis (73% vs. 59%; p = 0.03) at a mean follow-up of 18 years. We have described an angiogenic and osteoclastic reaction in the base of the growth plate in the proximity of the advance front of the tumor, which could facilitate the osteosarcoma invasion. It is also shown that the preoperative imaging method for examination is a valid approach for the decision to carry out epiphyseal preservation. Finally, we concluded that epiphyseal preservation combined with protective chemotherapy is an excellent clinical approach for selected patients with metaphyseal osteosarcoma.

A Cohort Study to Evaluate the Efficacy and Value of CT Perfusion Imaging in Patients with Metastatic Osteosarcoma after Chemotherapy

“…The rich vascular network provides sufficient oxygen and nutrients to tumor cells, and it is also a gateway for tumor metastasis, so the ability of angiogenesis is considered to be one of the markers of tumor aggressiveness. Tumor neovascularization plays an important role in the occurrence, development, invasion, and metastasis of osteosarcoma [ 10 , 11 ]. Understanding angiogenesis in osteosarcoma can help predict the prognosis of the tumor.…”

Epiphyseal distraction prior to resection in paediatric bone sarcomas

“…The same pronounced VEGF expression was found in tumours that crossed the physis. 15 These findings suggest that neovascularization is a relevant pathological change that helps tumour cells to cross the physis. The obtained results open the possibility of treating metaphyseal osteosarcoma with anti-angiogenic therapies, to halt the osteosarcoma invasion through the physis.…”

“…We found 73% (73 patients) of disease-free survival in osteosarcoma and 68% (47 patients) in Ewing's sarcoma at a mean follow-up of 15 years versus 59% in those cases in which the epiphysis could not be preserved. 15 In addition, patients whose epiphyses could not be preserved had more metastases at diagnosis. Both datasets suggest the important role of an early diagnosis.…”

What Do We Know about Survival in Skeletally Premature Children Aged 0 to 10 Years with Ewing Sarcoma? A Multicenter 10-Year Follow-Up Study in 60 Patients

“…This might result in longer patient delay and thus larger tumor size and more frequent metastases at time of diagnosis. In pediatric osteosarcoma and ES, time from initial symptoms to start of treatment matters in terms of survival and local recurrence rates [33,34]. However, in both osteosarcoma and ES, it has also been suggested that treatment delay would not influence outcome, so maybe biological behavior of these malignancies is more important for prognoses [35,36].…”