In an EORTC (European Organisation for Research and Treatment) study, Dr. Martin J. van den Bent, at Erasmus Medical Center in Rotterdam, Holland, and colleagues treated 368 patients with newly diagnosed anaplastic oligodendrogliomas with 59.4 Gy of radiotherapy or the same dose of RT followed by six cycles of procarbazine, lomustine, and vincristine (PCV) chemotherapy.
Menawhile, in a study for the Radiation Therapy Oncology Group (RTOG), Dr. Gregory Cairncross, with Foothills Medical Centre in Calgary, Alberta, Canada, and colleagues randomized 291 such patients to four cycles of PVC chemotherapy followed by 59.4 Gy of radiotherapy or radiotherapy alone.
Both studies are being published currently by the Journal of Clinical Oncology, online October 15.
In the European study, median overall survival among all the patients was significantly longer in the RT/PVC arm at 42.3 months versus 30.6 months in the RT-only group. Corresponding overall survival in the RTOG study was not significantly different at 4.6 vs 4.7 years.
However, in both studies, survival was markedly different among the subgroup of patients with codeleted tumors – ie, both the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q) are deleted.
Among these patients in the EORTC study, median overall survival has not yet been reached in the RT/PVC group, while in the RT-only group it is 112 months. Among a similar subgroup of patients in the RTOG study, corresponding survival figures are 14.7 years versus 7.3 years.
Both teams of researchers conclude that PCV plus RT may be especially effective for 1p/19q codeleted anaplastic oligodendrogliomas, although the RTOG authors caution that “this observation was derived from an unplanned analysis.”
Reuters Health asked Dr. Cairncross how this might affect the robustness of the finding. “I think this conclusion is very secure, especially given an identical finding by the EORTC,” he responded.
“In both trials,” he added, “the analysis of the effect of codeletion was, by necessity, post-hoc, because David Louis and I did not discover its clinical relevance (ie, highly associated with chemosensitivity in oligodendrogliomas) until 1998, 4 years after RTOG 9402 and the EORTC trial commenced. However, the need for the genetic analysis was always on our minds as the trials slowly accrued and follow-up ensued.”
Going forward, there are now at least two big clinical questions to be answered, Dr. Cairncross commented. First, “Can we substitute temozolomide (modern) for PCV (older regimen) and get the same excellent results in codeleted cases?”
The second question centers around how best to treat patients whose tumors do not have the codeletion. “The latter is not a trivial matter,” Dr. Cairncross explained, “because there were more long-term survivors after chemo-radiotherapy within the non-codeleted subset as well (25% vs 10% at 10 years) suggesting that another subgroup also benefit from combined treatment at diagnosis. We’re hard at work in the laboratory trying to find them.”
He added, “It will need to be a genetic marker because the tumors of longer and shorter survivors after chemo-radiotherapy are indistinguishable under the light microscope.”
The authors of the EORTC study have similar questions, and hope for answers from the currently ongoing CATNON (Concurrent and Adjuvant Temozolomide Chemotherapy in Non-1p/19q Deleted Anaplastic Glioma) study.
“In this EORTC study conducted in Europe, Australia, and North America, patients are treated with various combinations of radiotherapy and temozolomide,” they write in the conclusion of their paper. “The presence of an RT-only control arm will allow a further characterization of patients with grade 3 glioma who benefit from chemotherapy.”