Chemotherapeutic adjuvant treatment for osteosarcoma: where do we stand?

AIM: Since the introduction of chemotherapy, survival in localised high-grade osteosarcoma has improved considerably. However, there is still no worldwide consensus on a standard chemotherapy approach. In this systematic review evidence for effectiveness of each single drug and the role of response guided salvage treatment of adjuvant chemotherapy are addressed, whereas in a meta-analysis the number of drugs in current protocols is considered. METHODS: A systematic literature search for clinical studies in localised high-grade osteosarcoma was undertaken, including both randomised and non-randomised trials. Historical clinical studies from the pre-chemotherapy era were included for comparison purposes. RESULTS: Nine historical studies showed a long-term survival of 16% after only local treatment. Fifty single agent phase II studies showed high response rates for adriamycin (A, 43%), ifosfamide (Ifo, 33%), methotrexate (M, 32%), cisplatin (P, 26%) but only 4% for etposide (E). In 19 neo-adjuvant studies the mean 5-year event free survival (EFS) was 48% for 2-drug regimens and 58% for ⩾3 drug regimens, with a 5-year overall survival (OAS) of 62% and 70%, respectively. Meta-analysis showed that ⩾3 drug regimens including methotrexate plus adriamycin plus cisplatin (plus ifosfamide) (MAP(Ifo)) had significant better outcome (EFS: HR=0.701 (95% confidence interval [95% CI]: 0.615-0.799); OAS: HR=0.792 (95% CI: 0.677-0.926) than 2-drug regimens, but there was no significant difference between MAP and MAPIfo (or plus etoposide). Salvage of poor responders by changing drugs, or intensifying treatment postoperatively has not proven to be useful in this analysis. CONCLUSION: Meta-analysis in patients with localised high-grade osteosarcoma shows that 3-drug regimens, for example MAP are the most efficacious drug regimens.

Radiofrequency ablation of spinal osteoid osteoma: clinical outcome.

STUDY DESIGN: A prospective study on 24 patients with spinal osteoid osteoma treated with radiofrequency ablation (RFA). OBJECTIVE: To determine if and when computed tomography (CT)-guided RFA is a safe and effective treatment for spinal osteoid osteomas. SUMMARY OF BACKGROUND DATA: Surgery has been considered the standard treatment for spinal osteoid osteomas. Surgery may cause spinal instability, infection, and nervous injury. We evaluated CT-guided RFA as an alternative treatment. METHODS: A total of 28 RFA procedures in 24 patients with spinal osteoid osteoma were performed, using a 5-mm noncooled electrode. Clinical symptoms and spinal deformity were evaluated before and after the procedure. Unsuccessful treatment was defined as the presence of residual or recurrent symptoms. The mean follow-up was 72 months (range: 9-142 months). RESULTS: Nineteen (79%) patients were successfully treated after 1 RFA, and all except one after repeat RFA. One patient with nerve root compression needed further surgery. No complications were observed. Spinal deformity persisted in 3 of 7 patients after successful RFA. CONCLUSION: CT-guided RFA is a safe and effective treatment for spinal osteoid osteoma. Surgery should be reserved for lesions causing nerve root compression.

The healing pattern of osteoid osteomas on computed tomography and magnetic resonance imaging after thermocoagulation.

OBJECTIVE: To compare the healing pattern of osteoid osteomas on computed tomography (CT) and magnetic resonance imaging (MRI) after successful and unsuccessful thermocoagulation. MATERIALS AND METHODS: Eighty-six patients were examined by CT and 18 patients by dynamic gadolinium-enhanced MRI before and after thermocoagulation for osteoid osteoma. Thermocoagulation was successful in 73% (63/86) and unsuccessful in 27% (23/86) of patients followed by CT. Thermocoagulation was successful in 72% (13/18) of patients followed by MRI. After treatment, the healing of the nidus on CT was evaluated using different healing patterns (complete ossification, minimal nidus rest, decreased size, unchanged size or thermonecrosis). On MRI the presence of reactive changes (joint effusion, "oedema-like" changes of bone marrow and soft tissue oedema) and the delay time (between arterial and nidus enhancement) were assessed and compared before and after thermocoagulation. RESULTS: Complete ossification or a minimal nidus rest was observed on CT in 58% (16/28) of treatment successes (with > 12 months follow-up), but not in treatment failures. "Oedema-like" changes of bone marrow and/or soft tissue oedema were seen on MR in all patients before thermocoagulation and in all treatment failures. However, residual "oedema-like" changes of bone marrow were also found in 69% (9/13) of treatment successes. An increased delay time was observed in 62% (8/13) of treatment successes and in 1/5 of treatment failures. CONCLUSION: Complete, or almost complete, ossification of the treated nidus on CT correlated with successful treatment. Absence of this ossification pattern, however, did not correlate with treatment failure. CT could not be used to identify the activity of the nidus following treatment. The value of MR parameters to assess residual activity of the nidus was limited in this study.

Osteoid osteoma: factors for increased risk of unsuccessful thermal coagulation.

PURPOSE: To retrospectively identify risk factors that may impede a favorable clinical outcome after thermocoagulation for osteoid osteoma. MATERIALS AND METHODS: Informed consent (permission for the procedure and permission to use patient data for analysis) was obtained from all patients who met study criteria, and institutional review board did not require approval. Analysis included age, sex, size and location of osteoid osteoma, presence of calcified nidus, number of needle positions used for coagulation, coagulation time, accuracy of needle position, learning curve of radiologist, and previous treatment in 95 consecutive patients with osteoid osteoma treated with thermocoagulation. With chi(2) analysis, Fisher exact test, or unpaired Student t test and logistic regression analysis, 23 unsuccessfully treated patients were compared with 72 successfully (pain-free) treated patients. RESULTS: Parameters associated with decreased risk for treatment failure were advanced age (mean age, 24 years in treatment success group vs 20 years in treatment failure group) and increased number of needle positions during thermocoagulation. Estimated odds ratios were, respectively, 0.93 (95% confidence interval: 0.88, 0.99) and 0.10 (95% confidence interval: 0.02, 0.41). Patients with a lesion of 10 mm or larger seemed at risk for treatment failure (odds ratio = 2.68), but the 95% confidence interval of 0.84 to 8.52 included the 1.00 value. Needle position was inaccurate in nine of 23 patients with treatment failure; only one needle position was used in eight of these nine patients. Lesion location, calcification, sex, coagulation time, radiologist's learning curve, and previous treatment were not risk factors. CONCLUSION: Multiple needle positions reduce the risk of treatment failure in all patients and should especially, but not exclusively, be used in large (> or =10-mm) lesions or lesions that are difficult to engage to reduce the risk for unsuccessful treatment.

Osteoid osteoma: clinical results with thermocoagulation.

PURPOSE: To determine the clinical results in an unselected group of consecutive patients with osteoid osteoma treated with thermocoagulation. MATERIALS AND METHODS: In 97 consecutive patients with clinical and/or radiologic evidence of osteoid osteoma at any location, the clinical symptoms were assessed before and after thermocoagulation with computed tomographic guidance. A good response was defined as disappearance of symptoms that were manifested at presentation and attributed to osteoid osteoma. Clinical assessment was performed prior to discharge; within 2 weeks after the procedure; and at 3, 6, 12, and 24 months follow-up. After 24 months, a postal questionnaire was used for assessment. RESULTS: The mean clinical follow-up after the only or the last thermocoagulation session was 41 months (range, 5-81 months). Response was good after one session of thermocoagulation in 74 (76%) of 97 patients, and the 95% CI was 68% to 85%. Patients with persistent symptoms did well after repeated thermocoagulation (good response in 10 of 12 patients), but results of repeated thermocoagulation were poor in patients with recurrent symptoms (good response in five of 10). The overall success rate after one or two thermocoagulation procedures combined was 92% (89 of 97 patients), and the 95% CI was 86% to 97%. Complications were observed in two patients. CONCLUSION: Percutaneous thermocoagulation is a safe and effective method for treatment of osteoid osteoma at any location. Repeated thermocoagulation is successful in patients with persistent symptoms.