Abstract
A uniform classification of response to chemotherapy is essential to allow comparison of local effect and ultimate prognosis between different therapy schedules. We define a histological grading system for assessment of the response to chemotherapy in Ewing's sarcoma, based on the amount and architectural pattern of residual histologically viable-appearing tumour, the preferential sites of minimal residual tumour and the amount of tumour necrosis. Twenty-six consecutive patients with a biopsy-proven Ewing's sarcoma were treated with chemotherapy prior to surgery. The effect of chemotherapy was evaluated microscopically on the specimens obtained after surgery. Response to chemotherapy was classified as minimal or no effect (<10% tumour necrosis), moderate effect (solid areas of remnant viable tumour), minimal residual disease, and no evidence of disease (100% tumour necrosis or well-vascularized fibrous tissue). The subperiosteal area in particular, and, less frequently, soft tissues and intramedullary compartment were identified as sites of predilection for persistence of microscopic viable tumour foci, frequently depicted as pseudo-rosettes in a characteristic scattered pattern. Although it is not well known whether morphological viability of these residual clusters in Ewing's sarcoma indicates biological viability, accurate preoperative local staging, with special attention to preferential sites of residual viable tumour, is essential. The proposed grading system can be used to standardize assessment of chemotherapy in trials, and may serve as a standard for non-invasive monitoring of preoperative chemotherapy with magnetic resonance imaging.
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Meyers, PA, Heller, G, Healy, J, et al. Chemotherapy for nonmetastatic osteogenic sarcoma: the Memorial Sloan-Kettering experience. J. Clin Oncol 1992; 10: 5–15.
Jürgens H, Dunst J, Göbel U, et al. Improved survival in Ewing's sarcoma with response based local therapy and intensive chemotherapy. Proc Am Soc Clin Oncol 1991; 10: 316.
Woude HJ van der, Bloem JL, Holscher HC, et al. Monitoring the effect of chemotherapy in Ewing sarcoma of bone with MR imaging. Skeletal Radiol 1994; 23: 493–500.
Misdorp W, Hart G, Delemarre JFM, Voûte PA, Eijken JW van der. An analysis of spontaneous and chemotherapy-associated changes in skeletal osteosarcomas. J Pathol 1988; 156: 119–128.
Barbiere E, Emiliani E, Zini G, et al. Combined therapy of localized Ewing's sarcoma of bone: analysis of results in 100 patients. Int J Radiat Oncol Biol Phys 1990; 19: 1165–1170.
Hayes FA, Thompson EI, Hustu HO, Kumar M, Coburn T, Webber B. The response of Ewing's sarcoma to sequential cyclophosphamide and adriamycin induction therapy. J Clin Oncol 1983; 1: 45–51.
Huvos AG, Rosen G, Marcove RC. Primary osteogenic sarcoma: pathologic aspects in 20 patients after treatment with chemotherapy, en bloc resection, and prosthetic bone replacement. Arch Pathol Med 1977; 101: 14–18.
Rosen G, Nirenberg A. Chemotherapy for osteogenic sarcoma: an investigative method, not a recipe. Cancer Treat Rep 1982; 66: 1687–1697.
Sauer R, Jürgens H, Burgers JMV, Dunst J, Hawlicek R, Michaelis J. Prognostic factors in the treatment of Ewing's sarcoma. The Ewing's sarcoma study group of the German Society of Paediatric Oncology CESS 81. Radiol Oncol 1987; 10: 101–110.
Winkler K, Beron G, Kotz R, et al. Neoadjuvant chemotherapy for osteogenic sarcoma: results of a cooperative German/Austrian study. J Clin Oncol 1984; 2: 617–624.
Winkler K, Beron G, Delling G, et al. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumour response. J Clin Oncol 1988; 6: 329–337.
Denekamp J. Angiogenesis, neovascular proliferation and vascular pathophysiology as targets for cancer therapy. Br J Radiol 1993; 66: 181–196.
Picci P, Bacci G, Campanacci M, et al. Histologic evaluation of necrosis in osteosarcoma induced by chemotherapy: regional mapping of viable and nonviable tumor. Cancer 1985; 56: 1515–1521.
Rosen G, Caparros B, Huvos AG, et al. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer 1982; 49: 1221–1230.
Chaplin DJ. The effect of therapy on tumour vascular function. Int J Radiat Biol 1991; 60: 311–325.
Jain R. Determinants of tumor blood flow: a review. Cancer Res 1988; 48: 2641–2658.
Bacci G, Dallari D, McDonald D, et al. Neoadjuvant chemotherapy for localized Ewing's sarcoma of the extremities: preliminary results of a protocol which uses surgery (alone or followed by radiotherapy) for local control. Tumori 1989; 75: 456–462.
Bacci G, Toni A, Avella M, et al. Long-term results in 144 localized Ewing's sarcoma patients treated with combined therapy. Cancer 1989; 63: 1477–1486.
Bloem JL, Holscher HC, Taminiau AHM. Magnetic resonance imaging and computed tomography of primary malignant musculoskeletal tumors. In: Bloem JL, Sartoris DJ, eds. MRI and CT of the musculoskeletal system. Baltimore: Williams and Wilkins, 1991.
MacVicar AD, Olliff JFC, Pringle J, ross Pinkerton C, Husband JES. Ewing's sarcoma: MR imaging of chemotherapy-induced changes with histologic correlation. Radiology 1992; 184: 859–864.
Ambros IM, Ambros PF, Strehl S, Kovar H, Gadner H, SalzerKuntschik M. MIC2 is a specific marker for Ewing's sarcoma and peripheral primitive neuroectodermal tumors. Cancer 1991; 67: 1886–1893.
Marina NM, Etcubanas E, Parham DM, Bowman LC, Green A. Peripheral primitive neuroectodermal tumor (peripheral neuroepithelioma) in children- a review of the St. Jude experience and controversies in diagnosis and management. Cancer 1989; 64: 1953–1960.
Schmidt D, Herrmann C, Jürgens H, Harms D. Malignant peripheral neuroectodermal tumor and its necessary distinction from Ewing's sarcoma. Cancer 1991; 68: 2251–2259.
Hartman KR, Triche TJ, Kinsella TJ, Miser JS. Prognostic value of histopathology in Ewing's sarcoma. Long-term follow-up of distal extremity primary tumors. Cancer 1991; 67: 163–171.
Kushner BH, Hajdu SI, Gulati SC, Erlandson RA, Exelby PR, Lieberman PH. Extracranial primitive neuroectodermal tumors. Cancer 1991; 67: 1825–1829.
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van der Woude, H.J., Bloem, J.L., Taminiau, A.H.M. et al. Classification of histopathologic changes following chemotherapy in Ewing's sarcoma of bone. Skeletal Radiol. 23, 501–507 (1994). https://doi.org/10.1007/BF00223077
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DOI: https://doi.org/10.1007/BF00223077