Assessment of resection margins in bone sarcoma treated by neoadjuvant chemotherapy: Literature review and guidelines of the bone group (GROUPOS) of the French sarcoma group and bone tumor study group (GSF-GETO/RESOS)

Abstract

Background: Standardized reports are essential to meeting the bone sarcoma reference center certification requirements of the French National Cancer Institute (INCa). The usual classifications of the Musculoskeletal Tumor Society (MSTS), the American Joint Committee on Cancer (AJCC/IUCC) TNM R classification and the American College of Pathologists, are inexact inasmuch as they fail to include chemotherapy impact on tumor cells in assessing surgical margins. This leads to inconsistent interpretation by teams managing bone sarcoma. The present literature analysis sought to assess the limitations of existing classifications for purposes of standardized reporting of the management of surgical specimens from patients with osteosarcoma or Ewing sarcoma receiving neoadjuvant chemotherapy, by addressing the following questions: 1) What is the prognostic value of margins and chemotherapy response in the classifications? 2) What are the histologic changes induced by chemotherapy, with what impact on interpretation of margins?

Method: A PubMed literature analysis was performed, targeting the prognostic value of resection margin assessment, in September 2018. French bone pathology group (Groupe français des pathologistes osseux) and international guidelines on bone specimen management were referred to so as select items for a standardized report. Eight of the 523 articles retrieved met the study eligibility criteria.

Results: Minimal distance between tumor and surgical margin, with a>2mm threshold, seemed to be the optimal parameter for predicting local recurrence. Good chemotherapy response and appendicular skeletal location were associated with lower risk of local recurrence. None of the available classifications take into account the microscopic changes induced by chemotherapy in interpreting resection margins.

Discussion: To standardize practice, GROUPOS developed a standardized report for bone sarcoma specimens, considering the histopathologic changes in the tumor after neoadjuvant chemotherapy. The TNM R system was adapted and a threshold of>2mm was chosen as an acceptable limit to qualify surgical resection as safe (R0). R1 status (≤2mm) was subdivided into subgroups a, b and c, to include margin measurement in relation to the post-chemotherapy scar: R1a, resection within the scar; R1b, resection in healthy tissue,≤2mm from the scar and/or residual viable cells; and R1c, resection within the lesion in contact with viable cells or within coagulation necrosis areas. The GROUPOS members drew up this standardized report so as to ensure a common language, improving bone sarcoma management in specialized centers. Reliable data can thus be established for national and international multicenter studies.

Level of evidence: IV.

Keywords: Bone sarcoma; Chemotherapy; Ewing sarcoma; Margins; Osteosarcoma.