Jelic, S.

Pavlidis, N.

Stupp, R.

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ESMO Minimum Clinical Recommendations for diagnosis,treatment and follow-up of malignant gliomaIncidence. The incidence of malignant glioma is 5–7/100 000. Malig-nant glioma may develop at all ages, the peak incidencebeing in the fifth and sixth decades of life.Diagnosis. Malignant glioma comprises glioblastoma multiforme(WHO grade IV), anaplastic astrocytoma (WHO grade III),mixed anaplastic oligoastrocytoma (WHO grade III), andanaplastic oligodendroglioma (WHO grade III). Diagnosisafter biopsy or tumor resection is made according to therevised WHO classification.Staging and risk assessment. Staging includes imaging of the brain, ideally with MRI. Ifrepeat imaging is deemed necessary to determine residualdisease, it should be done within 24–48 h after surgery.Lumbar puncture is generally not necessary and staging ofother organs is not needed.. Other than tumor grade, good performance status and anintact neurological function, tumor resection, and age <50years have been identified as more favorable prognosticfactors.. Prognosis depends on tumor grade. Glioblastoma carry theworst prognosis, while pure oligodendroglioma tend to havea better outcome and improved response to therapy. Mixedanaplastic oligoastrocytoma behave similarly to anaplasticastrocytoma with an intermediate prognosis.Treatment plan. Patients should be evaluated by a specialized multidisciplin-ary team. Special consideration needs to be given to per-formance status and neurological function.Newly-diagnosed patients. Surgery is commonly the initial therapeutic approach fordebulking and obtaining tissue for diagnosis. Tumor resec-tion is of prognostic value, but attempting maximal tumorresection remains controversial [IV, C]. Implantation of che-motherapy-impregnated wafer (BCNU-polymer) into theresection cavity has shown only a marginal benefit [II, B].. Fractionated focal radiotherapy (60 Gy, 2 Gy 30; or equiv-alent doses/fractionations) is the standard treatment afterresection or biopsy [I, A]. Escalating doses beyond 60 Gyhas not been shown of value. In elderly patients or patientswith a low performance status shorter hypofractionated regi-mens (e.g. 3 Gy 10) are commonly proposed.. Adjuvant chemotherapy with procarbazine, lomustine(CCNU) and vincristine (PCV regimen) has failed toimprove survival in prospective randomized studies [I, A].Nevertheless, based on a large meta-analysis [III, B] nitro-sourea-based chemotherapy may improve survival inselected patients.. Concomitant and adjuvant temozolomide chemotherapy hasdemonstrated to significantly improve median and 2-yearsurvival in a large randomized trial [I, A]. Selecting patientslikely to benefit from therapy based on MGMT gene methyl-ation has been suggested [II, B].Recurrent disease. Some benefit of chemotherapy has been shown for patientswith an adequate performance status who have not receivedprior adjuvant cytotoxic therapy. Anaplastic astrocytomasare more likely to respond to chemotherapy than glioblas-toma. [III, B].. Repeat surgery and implantation of chemotherapy-impreg-nated polymers may prolong survival in selected patients[II, B].Oligodendroglioma. Oligodendroglioma carry a somewhat better prognosis. Inparticular the subgroup of patients with a deletion onchromosome 1p and 19q seem to have a longer survival andbetter response to chemotherapy. However, at the currenttime 1p/19q LOH determination should not be routinely per-formed and should not influence the initial treatment rec-ommendations. In patients with recurrent oligodendroglioma,chemotherapy should be considered [II, B].Response evaluation. If response is evaluated, it should be done with MRI. Con-trast enhancement and presumed tumor progression on ima-ging 4–8 weeks after the end of radiotherapy may be animaging artifact due to changes in the blood-brain barrierpermeability and should be confirmed 4 weeks later with asecond MRI.. Response to chemotherapy is evaluated according to theWHO criteria, but should also include an assessment of theneurological function and corticosteroid use (Macdonaldcriteria).Annals of Oncology 16 (Supplement 1): i64–i65, 2005doi:10.1093/annonc/mdi834q 2005 European Society for Medical OncologyFollow-up. Follow-up consists of a clinical evaluation with particularattention to neurological function, seizures or seizureequivalents and corticosteroid use. Patients should betapered off steroid use as early as possible.. Laboratory tests are not indicated unless patient is receivingchemotherapy (blood counts), corticosteroids (glucose) oranti-epileptic drugs (blood counts, liver function tests).NoteLevels of Evidence [I–V] and Grades of Recommendation[A–D] as used by the American Society of Clinical Oncologyare given in square brackets. Statements without grading wereconsidered justified standard clinical practice by the expertauthors and the ESMO faculty.Literature1. DeAngelis LM. Medical Progress: Brain Tumors. N Engl J Med2001; 344: 114–123.2. Stewart LA. Chemotherapy in adult high-grade glioma: a systematicreview and meta-analysis of individual patient data from 12 random-ised trials. Lancet 2002; 359: 1011–1018.3. Medical Research Council Brain Tumor Working Party. Randomizedtrial of procarbazine, lomustine and vincristine in the adjuvant treat-ment of high-grade astrocytoma: A Medical Research Council trial. JClin Oncol 2001; 19: 509–518.4. Stupp R, Mason WP, van den Bent MJ et al. on behalf of the Euro-pean Organisation for Research and Treatment of Cancer BrainTumor and Radiotherapy Groups and National Cancer Institute ofCanada Clinical Trials Group. Concomitant and adjuvant temozolo-mide and radiotherapy for newly diagnosed glioblastoma multiforme.New Engl J Med 2005; 352: 987–996.5. Hegi ME, Diserens AC, Godard S et al. Clinical trial substantiates thepredictive value of O-6-methylguanine-DNA methyltransferase pro-moter methylation in glioblastoma patients treated with temozolo-mide. Clin Cancer Res 2004; 10: 1871–1874.6. Westphal M, Hilt DC, Bortey E et al. A phase 3 trial of local che-motherapy with biodegradable carmustine (BCNU) wafers (Gliadelwafers) in patients with primary malignant glioma. Neuro-oncol 2003;5: 79–88.7. Yung WK, Albright RE, Olson J et al. A phase II study of temozolo-mide vs. procarbazine in patients with glioblastoma multiforme atfirst relapse. Br J Cancer 2000; 83: 588–593.8. Brandes AA, Tosoni A, Basso U et al. Second-line chemotherapywith irinotecan plus carmustine in glioblastoma recurrent or progress-ive after first-line temozolomide chemotherapy: a phase II study ofthe Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO). J ClinOncol 2004; 22: 4727–4734.9. van den Bent M, Chinot OL, Cairncross JG. Recent developments inthe molecular characterization and treatment of oligodendroglialtumors. Neuro-Oncol 2003; 5: 128–138.10. van den Bent MJ, Taphoorn MJ, Brandes AA et al. Phase II study offirst-line chemotherapy with temozolomide in recurrent oligodendro-glial tumors: the European Organization for Research and Treatmentof Cancer Brain Tumor Group Study 26 971. J Clin Oncol 2003; 21:2525–2528.11. Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG. Responsecriteria for phase II studies of supratentorial malignant glioma. J ClinOncol 1990; 8: 1277–1280.12. Wong ET, Hess KR, Gleason MJ et al. Outcomes and prognostic fac-tors in recurrent glioma patients enrolled onto phase II clinical trials.J Clin Oncol 1999; 17: 2572–2578.13. Lacroix M, Abi-Said D, Fourney DR et al. A multivariate analysis of416 patients with glioblastoma multiforme: prognosis, extent of resec-tion, and survival. J Neurosurg 2001; 95: 190–198.Coordinating authors for the ESMO Guidelines Task Force: R. Stupp1,N. Pavlidis2 & S. Jelic31Invited author, University Hospital (CHUV), Multidisciplinary OncologyCenter, 1011 Lausanne, Switzerland; 2Assigned task force member,University of Ioannina, Dept. Medical Oncology, 45 110 Ioannina,Greece; 3Assigned task force member, Institute of Oncology andRadiology of Serbia, Department of Medical Oncology, Pasterova 14,11000 Belgrade, SerbiaApproved by the ESMO Guidelines Task Force: December 2004.Correspondence to:ESMO Guidelines Task ForceESMO Head OfficeVia La Santa 7CH-6962 LuganoSwitzerlandi65

ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of malignant glioma

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