EVALUATING GLIOMA THERAPIES - MODELING TREATMENTS AND PREDICTING OUTCOMES

Background: Intra-arterial chemotherapy with carmustine (BCNU) and int erstitial radiation therapy with the use of stereotactically placed I- 125 sources are aggressive local therapies for malignant glioma, These therapies emerged in the 1980s and both appeared promising in phase I I studies but yielded disappointing results in subsequent randomized c ontrolled trials by the Brain Tumor Cooperative Group (BTCG), Florell and colleagues had prepared us for the possibility that brachytherapy would have less impact on survival than anticipated from the phase II experience by demonstrating that patients who were judged eligible for interstitial radiation, but treated conventionally, lived significant ly longer than those who were ineligible and had better than average o utcomes, Purpose: To further examine the impact of patient selection o n outcome, we used the database of Florell et al, to assess the surviv al of patients with malignant glioma who were eligible or ineligible f or chemotherapy by three intra-arterial methods, one of which was simi lar to that employed by the BTCG in its randomized, controlled trial e valuating intra-arterial BCNU, Methods: The medical records and comput ed tomography (CT) scans of 102 consecutive patients with malignant gl ioma receiving standard treatment (i,e,, maximum feasible surgical res ection, external-beam radiotherapy, and often adjuvant systemic chemot herapy) at a single cancer center in Canada during the calendar years 1988 and 1989 were used for this analysis, Based on CT imaging and bli nd to outcome, an interventional neuroradiologist decided which patien ts were eligible or ineligible for intra-arterial chemotherapy via inj ection of two major arteries, via injection of one major artery, or vi a selective middle-cerebral artery injection, A Karnofsky performance score of greater than or equal to 60 was required, The percent of elig ible patients, the median survival time, and the distribution of progn ostic factors were analyzed for each group of eligible and ineligible patients, Median survival times were compared with the use of the gene ralized Wilcoxon (Breslow) test, All P values were based on two-tailed tests, Results: For two-vessel treatment, 72.5% of the patients (74 o f 102) were eligible; the eligible patients on average lived longer th an the ineligible patients (14.8 versus 3.5 months; P<.00001), For one -vessel treatment, 48% of the patients (49 of 102) were eligible; agai n, the eligible patients lived longer than the ineligible patients (18 .4 versus 5.1 months; P<.00001). For middle-cerebral artery treatment, 30% of the patients (31 of 102) were eligible, and these eligible pat ients did live somewhat longer than the ineligible patients, but this result did not reach statistical significance (13.6 versus 9.9 months; P = .1304), Trends were similar for patients with glioblastoma multif orme and anaplastic glioma, The median duration of survival was 11.4 m onths for all patients, Conclusions: Patients who were eligible for in tra-arterial chemotherapy lived significantly longer or somewhat longe r (depending on the selection criteria used) than patients who were in eligible and had better than expected outcomes, Patients who were judg ed eligible for intra-arterial chemotherapy by the two-vessel method a nd the control group in the BTCG phase III trial of intra-arterial che motherapy had similar median survival times (14.8 versus 14. 0 months) , Implications: Modeling treatments with the use of a comprehensive cl inical and imaging database of unselected, conventionally treated pati ents may help investigators decide if new therapies warrant definitive evaluation in randomized trials by measuring the degree to which pati ent selection may have enhanced phase II study outcomes.