title: Posttreatment histology and microcirculation status of osteogenic sarcoma after a neoadjuvant chemo- and radiotherapy in combination with local electromagnetic hyperthermia.
abstract: BACKGROUND
  Many biological attributes of tumors (including regional blood flow and microcirculation) can deteriorate the homogeneity of heat distribution and temperature elevation during hyperthermia. We analyzed the connection between the microcirculation status of osteogenic sarcomas and the posttreatment histology after neoadjuvant chemotherapy, irradiation and local hyperthermia.
  
  
  METHODS
  62 patients with histologically verified osteosarcoma (35 men, 27 women, age 9-53, average 21 years) were enrolled in the retrospective pathohistological study. 61 patients were evaluable. In 72.6% of cases the tumor was localized in bones forming knee joints. All patients received neoadjuvant treatment [6 hyperthermias (60 min, 42-45 degrees C), daunorubicin 30-50 mg/m(2), 6 infusions, adriamycin or cisplatin 30 mg/m(2) for 3 days or once 90 mg/m(2) monochemotherapy before the hyperthermic procedure; subsequently gamma-therapy, 20-36 Gy] followed by surgery. From archives, a control group was formed of 20 therapy-naive tumors. Resected tumors were histologically examined for assessment of spontaneous and therapeutically induced alterations. For analysis of the functionality status of microcirculation on histological cuts, 40 tumors (without selection) were investigated: 10 controls and 10 cases each with minimal, subtotal and total posttreatment alterations.
  
  
  RESULTS
  Chemotherapy and radiotherapy in combination with local hyperthermia induced a distinct damage to osteosarcoma. In 39.3 and 35.7% of cases there was subtotal and total devitalization of tumor parenchyma, respectively. Thrombosis of magistral and middle vessels, stasis in the microcirculation tree (collapse), damage to intimal vessels and endothelial cells, and necrotic alterations of the vessel walls appeared predominantly in central areas of tumors. Tumors with minimal devitalization of the parenchyma had a share of nonfunctional vessels ranging from 10.6 to 61.7%, mean 29.7%. In tumors with subtotal necrosis, between 34.5 and 72.0% (mean 49.46%) of vessels were nonfunctional (stasis, thrombosis). In 10 cases with 100% necrosis of the osteosarcoma parenchyma, a mean of 56.05% of nonfunctional vessels was registered (12.3-83.0%). In the control group, between 2.85 and 73.4% (mean 21.69%) of vessels showed damage to the microcirculation.
  
  
  CONCLUSIONS
  There is a direct correlation between deterioration of the microcirculation in osteosarcoma and thermo-radiochemotherapy- induced tissue alteration; the devitalization grade is directly proportional to the number of nonfunctional vessels in the tumor.
authors.affiliation: Klinik St. Georg, Bad Aibling, Germany. j.bogovic@t-online.de
authors.forename: J
authors.initials: J
authors.lastname: Bogovic
authors.forename: F
authors.initials: F
authors.lastname: Douwes
authors.forename: G
authors.initials: G
authors.lastname: Muravjov
authors.forename: J
authors.initials: J
authors.lastname: Istomin
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D001842:Bone and Bones / Q000098:blood supply / Q000473:pathology; D002648:Child; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D008833:Microcirculation / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D008875:Middle Aged; D009336:Necrosis; D012516:Osteosarcoma / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D011859:Radiography; D018714:Radiotherapy, Adjuvant