1p/19q loss within oligodendroglioma is predictive for response to first line temozolomide but not to salvage treatment.
BACKGROUND
Combined loss of 1p/19q predicts an almost 100% response rate to first line procarbazine, CCNU and vincristine chemotherapy (PCV) chemotherapy in oligodendroglial tumours. We assessed the impact of 1p and 19q loss on the outcome to first line temozolomide (TMZ) chemotherapy and to second line PCV or TMZ in progressive oligodendroglial tumours.


METHODS
Tumour samples from patients included in two prospective EORTC studies on first line and second line TMZ chemotherapy in recurrent oligodendroglioma were used for this study. Most patients in the first line TMZ trial received PCV at further progression. Loss of 1p and 19q was assessed on paraffin embedded tumour samples by fluorescent in situ hybridisation with locus specific probes for 1p36 and 19q13.


RESULTS
Losses of 1p and 19q were mainly observed in morphologically classical oligodendrogliomas (OD). Thirteen out of 18 patients with 1p loss (72%) responded to first line temozolomide (p<0.01). Both response to second line salvage PCV or to second line temozolomide was limited, even in patients with combined 1p/19q loss. Patients with tumours with 1p loss treated with salvage PCV had improved PFS (p<0.05). More patients with 1p loss were alive at 60 and 120 months after initial surgery (p<0.001).


CONCLUSIONS
Combined 1p/19q loss is mainly observed in classical OD. Responses to first line temozolomide are strongly correlated to loss of 1p. Response to second line alkylating treatment is modest even in tumours with 1p/19q loss. For further improvement of outcome in OD novel treatments are needed.
Kouwenhoven
Mathilde C M
MC
Department of Neuro-Oncology, Daniel den Hoed Oncology Center, P.O. Box 5201, 3008AE Rotterdam, The Netherlands.
Kros
Johan M
JM
French
Pim J
PJ
Biemond-ter Stege
Elize M
EM
Graveland
Wilfried J
WJ
Taphoorn
Martin J B
MJ
Brandes
Alba A
AA
van den Bent
Martin J
MJ
D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D017322:Clinical Trials, Phase II as Topic; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015337:Multicenter Studies as Topic; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009837:Oligodendroglioma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D011446:Prospective Studies; D016879:Salvage Therapy; D016019:Survival Analysis; D000077204:Temozolomide; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide