Anne Gomez-Brouchet1, Eric Mascard2, Aurore Siegfried3, Gonzague de Pinieux4, Nathalie Gaspar5, Corinne Bouvier6, Sébastien Aubert7, Perrine Marec-Bérard8, Sophie Piperno-Neumann9, Béatrice Marie10, Frédérique Larousserie11, Christine Galant12, Fabrice Fiorenza13, Philippe Anract14, Jérôme Sales de Gauzy15, François Gouin16. 1. Département de pathologie, IUCT-oncopole, CHU de Toulouse and université de Toulouse, 1, avenue Irène Joliot Curie, 31059 Toulouse cedex 9, France. Electronic address: brouchet.anne@chu-toulouse.fr. 2. Département de chirurgie orthopédique pédiatrique, hôpital-Necker, 149, rue de Sèvres, 75015 Paris, France. 3. Département de pathologie, IUCT-oncopole, CHU de Toulouse and université de Toulouse, 1, avenue Irène Joliot Curie, 31059 Toulouse cedex 9, France. 4. Service d'anatomie et cytologie pathologiques et université de Tours, CHRU de Tours, Avenue de la République, 37170 Chambray-lès-Tours, France. 5. Département de cancérologie de l'enfant et l'adolescent, Gustave-Roussy cancer campus, 114, rue Edouard Vaillant, 94800 Villejuif, France. 6. Département de pathologie, CHU la Timone, 278, rue Saint-Pierre, 13005 Marseille, France. 7. Université de lille - institut de pathologie, centre de biologie pathologie, 1, rue Philippe Marache, 59000 Lille, France. 8. Département d' oncologie pédiatrique, IHOPe/Centre Léon Bérard, 28, promenade Léa et Napoléon Bullukian, 69008 Lyon, France. 9. Département d'oncologie médicale, institut Curie, 26, rue d'Ulm, 75005 Paris, France. 10. Département de Pathologie, CHU Nancy, 25, rue Lionnois, 54000 Nancy, France. 11. Service de pathologie et université Paris Descartes, AP-HP, hôpital Cochin, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France. 12. Service d'anatomie pathologique des cliniques universitaires Saint-Luc, 10, avenue Hippocrate, 1200 Brussels, Belgium. 13. Département de chirurgie orthopédique, CHU de Limoges, 2, avenue Martin Luther King, 87000 Limoges, France. 14. Département de chirurgie orthopédique, CHU de Cochin, AP-HP, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France. 15. Département de chirurgie orthopédique pédiatrique, hôpital-Mère-Enfant, CHU Toulouse, 330, avenue de Grande Bretagne, 31300 Toulouse, France. 16. Centre Léon-Bérard, CHU Nantes, Nantes/Inserm, UMR 1238, Phy-Os, université de Nantes, 28, rue Laennec, 69008 Lyon France.
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.
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.
Authors: Denis Ehrl; Nikolaus Wachtel; David Braig; Constanze Kuhlmann; Hans Roland Dürr; Christian P Schneider; Riccardo E Giunta Journal: J Pers Med Date: 2022-04-01