Combined treatment with intensive PCV followed by high-dose chemotherapy with autologous stem cell support achieved excellent disease control and preservation of neurologic function in this cohort of patients with anaplastic and aggressive oligodendrogliomas. At present, there is a considerable variety of treatment options for patients with newly diagnosed anaplastic oligodendroglioma. Many patients are treated with focal radiotherapy alone, and the results of a recently reported Radiation Therapy Oncology Group (RTOG) study would support this strategy (Cairncross et al., 2004
). The chemosensitivity of oligodendrogliomas has persuaded many practitioners to offer chemotherapy alone, usually temozolomide or PCV, and defer radiotherapy until relapse; several reported series support this approach; however, other reports suggest that chemotherapy alone is inadequate to provide long-term disease control (Chibbaro et al., 2004; Paleologos et al., 1999; Soffietti, 2004
). This protocol was designed to replace radiotherapy with a myeloablative dose of thiotepa in an effort to eradicate microscopic disease and provide nonneurotoxic antitumor therapy. With long-term follow-up, more than half of the patients remain in remission without any evidence of treatment-related neurologic injury.
Less than half of the patients who completed the planned therapy developed tumor progression. Relapse rarely occurred within the first year of follow-up but has been observed as late as seven years after completion of therapy, which indicates the need for long-term follow-up. Furthermore, most patients (83%) whose disease relapsed responded to salvage therapy with control of their recurrent tumor for six months or longer. It would appear that both radiotherapy and additional salvage chemotherapy, including temozolomide, could induce further disease control.
Surviving patients in a continuous CR are functioning at a high level that is at or close to their level of function prior to tumor diagnosis. Detailed neurocognitive testing and quality-of-life measures were not included in this protocol, and it is therefore possible that subtle cognitive deficits or reduced quality of life were not detected. However, no clinically apparent neurologic deterioration or treatment-induced myelodysplasia have developed.
Combined allelic loss of chromosomes 1p and 19q are associated with durable responses to chemotherapy in oligodendroglial neoplasms (Cairncross et al., 1998; Ino et al., 2001; Smith et al., 2000
). Our study did not analyze the molecular genetic status of our patient’s tumors prospectively; however, since our initial report, we obtained genetic information regarding the molecular status on 10 of our patients. The available data suggest that most of our patients had 1p and/or 19q LOH and excellent response to therapy; however, several with combined allelic loss had a brief response to chemotherapy and varying duration of survival after salvage therapy. Furthermore, one patient with intact 1p and 19q had a durable response to initial chemotherapy and prolonged survival following salvage radiotherapy. This highlights the difficulty of predicting an individual patient’s treatment response based on prognostic genetic factors and emphasizes the importance of analyzing the prognostic implications of 1p and 19q status prospectively in order to develop appropriate therapeutic guidelines. Recent publications suggest that other genetic alterations play an important role, either complimenting or negatively impacting the effect of 1p and 19q LOH (Ino et al., 2001
). Other cases of excellent outcome in patients with intact 1p and 19q further indicate that other genetic alterations are likely important prognostic markers of response to therapy and overall outcome (Ino et al., 2001
These encouraging data suggest that some high-grade oligodendrogliomas may be treatable by chemotherapy alone and that effective treatment can result in excellent neurologic function for many years. These results should be interpreted in the context of the relatively small sample size, young age, and excellent performance status of our patients. Careful selection of patients who are medically appropriate to be considered for high-dose chemotherapy with autologous stem cell support introduces a selection bias that may be reflected in the long-term outcome of our patients. However, this is the group of patients who may derive the most benefit from an aggressive treatment strategy that defers radiotherapy in an effort to avoid delayed cognitive impairment.