Results of the Scandinavian Sarcoma Group XIV protocol for classical osteosarcoma: 63 patients with a minimum follow-up of 4 years

Background and purpose The Scandinavian Sarcoma Group (SSG) XIV protocol is based on experience from previous SSG trials and other osteosarcoma intergroup trials, and has been considered the best standard of care for patients with extremity localized, non-metastatic osteosarcoma. We analyzed the outcome in 63 consecutive patients. Patients and methods From 2001 through 2005, 63 patients recruited from centers in Sweden, Norway, and Finland were included. They received preoperative chemotherapy consisting of 2 cycles of paired methotrexate (12 g/m(2)), cisplatin (90 mg/m(2)), and doxorubicin (75 mg/m(2)). 3 cycles were administered post-operatively, and poor histological responders were given 3 additional cycles of ifosfamide (10-12 g/m(2)) as a salvage strategy. Results With a median follow-up of 77 months for survivors, the estimated metastasis-free and sarcoma-related survival at 5 years was 70% and 76%, respectively. 53 patients were treated with limb salvage surgery or rotationplasty and 2 patients experienced a local recurrence. 3 toxic deaths were recorded, all related to acute toxicity from chemotherapy. The 5-year metastasis-free survival of poor histological responders receiving add-on treatment with ifosfamide was 47%, as compared to 89% for good histological responders. Interpretation Outcome from the SSG XIV protocol compares favorably with the results of previous SSG trials and other published osteosarcoma trials. However, salvage therapy given to poor responders did not improve outcome to a similar degree as for good responders. In a multi-institutional setting, more than four-fifths of the patients were operated with limb salvage surgery or rotationplasty, with few local recurrences

Studies of cerebral blood flow and cerebrospinal fluid in childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and more than 80% of the patients are cured today. Treatment might cause side effects and central nervous system (CNS) irradiation has been replaced by systemic high-dose methotrexate (MTX) and intrathecal (IT) MTX due to the risk of late effects. However, treatment without CNS irradiation is also neurotoxic and might cause brain damage. Three patients developed subacute neurotoxicity, one after IT MTX and two after HDMTX including IT MTX. All showed impaired regional cerebral blood flow (rCBF) when examined by single photon emission computed tomography (SPECT). The patients improved within a few days during treatment with the Ca2+-channel blocker nimodipine and all recovered completely. Another three patients, without neurological symptoms, were examined at different phases of ALL treatment and all had disturbances in rCBF. The heterogeneous cerebral hypoperfusion was however less pronounced than in the patients with symptoms. Twenty-five patients were examined during remission induction with prednisolone, doxorubicin, vincristine and IT MTX. Sixteen of these patients were first examined before start of treatment and nine during the first week. None had any neurologic symptoms but rCBF had deteriorated in all patients when re-examined after four weeks. The nine patients examined during the first week had heterogeneous cerebral hypoperfusion already at the first examination but to a lesser degree than at four weeks when the two groups showed similar results. Fourteen of the twenty-five patients were re-examined seven years later, i.e. five years after cessation of treatment. Eleven had normalized rCBF, one had improved, one was unchanged and the last one had sequelae after a stroke. Impact on CNS can also be studied by analyzing neurochemical markers of brain damage in cerebrospinal fluid (CSF). Samples were collected before start of treatment, at day 8, at day 15 and at day 29. The levels of three brain specific proteins increased during remission induction indicating damage to neurons and glia cells. Neuron-specific enolase (NSE), a marker of neurons, reached the highest level at day 8. Glia fibrillary acidic protein (GFAp), a marker of astrocytes, and the light subunit of neurofilament protein (NFp), a marker of axons, reached the highest level at day 29. Analyses of ascorbyl radical (AsR) as a marker of oxidative stress were not conclusive