Subgroup Of Astrocytomas Research Articles

Individualized discrimination of tumor progression from treatment-related changes in different types of adult-type diffuse gliomas using [11C]methionine PET.

This study aimed to assess the ability of [11C]methionine (MET) PET in distinguishing between tumor progression (TP) and treatment-related changes (TRCs) among different types of adult-type diffuse gliomas according to the 2021 World Health Organization classification and predict overall survival (OS). We retrospectively selected 113 patients with adult-type diffuse gliomas with suspected TP who underwent MET PET imaging. Maximum and mean tumor-to-background ratios (TBRmax, TBRmean) and metabolic tumor volume (MTV) were calculated. Diagnoses were verified by histopathology (n = 50) or by clinical/radiological follow-up (n = 63). The diagnostic performance of MET PET parameters was evaluated through receiver operating characteristic (ROC) analysis and area under the curve (AUC) calculation. Survival analysis employed the Kaplan-Meier method and Cox proportional-hazards regression. TP and TRCs were diagnosed in 76 (67%) and 37 (33%) patients, respectively. ROC analysis revealed TBRmax had the best performance in differentiating TP from TRCs with a cut-off of 1.96 in IDH-mutant astrocytoma (AUC, 0.87; sensitivity, 93%; specificity 69%), 1.80 in IDH-mutant and 1p/19q-codeleted oligodendroglioma (AUC, 0.96; sensitivity, 100%; specificity, 89%), and 2.13 in IDH wild-type glioblastoma (AUC, 0.89; sensitivity, 89%; specificity, 78%), respectively. On multivariate analysis, higher TBRmean and MTV were significantly correlated with shorter OS in all IDH-mutant gliomas, as well as in IDH-mutant astrocytoma subgroup. This work confirms that MET PET has varying diagnostic performances in distinguishing TP from TRCs within three types of adult-type diffuse gliomas, and highlights its high diagnostic accuracy in IDH-mutant and 1p/19q-codeleted oligodendroglioma and potential prognostic value for IDH-mutant gliomas, particularly IDH-mutant astrocytoma.

Abstract 4020: Methylation analysis of matched primary and recurrent IDH-mutant astrocytoma; an update from the GLASS-NL consortium

Abstract INTRODUCTION. Diffuse gliomas are the most frequent and devastating primary CNS tumors in adults. Standard treatment has limited efficacy and without exception these gliomas recur. The evolutionary processes that drive progression in glioma of the IDH-mutant astrocytoma subgroup, remain unclear. The GLASS-NL consortium was initiated to gain insight into the molecular mechanisms underlying glioma evolution and to identify markers of progression in IDH-mutant astrocytomas. Such markers can ultimately assist clinical decision making. Here, we present the results of genome wide DNA-methylation profiling of samples included in the GLASS-NL study. METHODS. 110 adult patients were identified with an IDH-mutant, 1p19q non-codeleted, astrocytoma at first diagnosis. All patients underwent surgical resection of the tumor at least twice, separated by >6 months with a median of 41.9 months (IQR:26.5-65.9). After surgical resection of the initial tumor, 63% and 22% of the patients were treated with radiotherapy or chemotherapy respectively. DNA-methylation profiling was performed on 235 samples from 103 patients, using the Illumina Infinium MethylationEPIC BeadChip array. Copy number alterations (CNAs) were extracted from these data. Methylation subclasses were determined according to Capper et al. (Nature, 2018). Overall survival (OS) was measured from date of initial surgery. RESULTS. Of all primary tumors, 85 (87%) of the tumor samples were assigned to the A_IDH (‘low grade’) methylation subclass and 10 (10%) to the A_IDH_HG (‘high grade’) subclass. The relative proportion of high grade tumors increased ~three-fold at tumor recurrence (32/101, 32%) and even further in the second recurrence (15/29, 52%). The high grade subclass of the recurrent, but not the initial tumor sample, was negatively associated with OS (p < 0.0001). The overall DNA-methylation levels of recurrent samples were lower than that of initial samples. This difference is explained by the increased number of high grade samples at recurrence, since near identical DNA-methylation levels were observed in samples that remained low grade. Analysis of CNAs revealed several chromosomal arms and bands that were more frequently altered in samples of the high grade methylation subclass compared to low grade. In addition, gains and losses of specific genes, such as homozygous deletion (HD) of CDKN2A/B, were more frequent in high grade samples. Overall DNA-methylation levels of recurrent samples with CDKN2A/B HD were lower than that of samples without this deletion. However, CDKN2A/B HD alone does not fully explain DNA-demethylation at malignant progression and other molecular aberrations are likely to contribute as well. CONCLUSION. Longitudinal methylation profiling analysis of IDH-mutant astrocytoma reveals a shift towards a higher grade at tumor recurrence coinciding with reduced genome-wide DNA-methylation levels. Citation Format: Wies Rijan Vallentgoed, Anneke Niers, Karin van Garderen, Martin van den Bent, Erik van Dijk, Kaspar Draaisma, Paul van Eijk, Iris de Heer, Mathilde Kouwenhoven, Johan Kros, Wendy de Leng, Ivonne Martin, Pierre Robe, Marion Smits, Mircea Tesileanu, Hinke van Thuijl, Roel Verhaak, Bart Westerman, Mark van de Wiel, Bauke Ylstra, Pieter Wesseling, Pim French. Methylation analysis of matched primary and recurrent IDH-mutant astrocytoma; an update from the GLASS-NL consortium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4020.

Gene expression profiling of 19q-loss astrocytomas suggest a specific pattern associated with the better prognosis.

We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. The aim of this study was to further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their relatively benign clinical behavior. We compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. By comparing expression levels of genes of 19q-loss astrocytomas to those of 19q-intact astrocytomas, 102 up-regulated genes and 162 down-regulated genes were extracted. The down-regulated genes clustered heavily to 19q and 4p while the up-regulated genes clustered to 4q. It was noteworthy that fibroblast growth factor 1 associated with stem cell maintenance and multiple genes associated with glioma progression were down-regulated in 19q-loss astrocytomas, and these results were validated with the independent TCGA data set. On t-SNE analysis of the 19q-loss astrocytomas with other IDH-mutant glioma subgroups from the TCGA datasets, the expression pattern of the 19q-loss astrocytomas showed no shift toward oligodendrogliomas with 1p/19q codeletion but rather constituted a subgroup of astrocytoma. These findings suggested that 19q-loss in astrocytomas is more likely acquired event rather than an early event in oncogenesis like the 1p/19q-codeletion in oligodendrogliomas, and that the biological features of 19q-loss astrocytomas are possibly related to differentially expressed genes associated with stem cell maintenance and glioma progression.

PATH-11. PROGNOSTIC SIGNIFICANCE OF EPIGENETIC SUBTYPES AND CpGs ASSOCIATED WITH PROGRESSION TO G-CIMP LOW IN THE EORTC RANDOMIZED PHASE III INTERGROUP CATNON

Abstract BACKGROUND Uncontrolled studies have suggested that methylation-based epigenetic subtypes can be used for prognostication of glioma. We used the prospective randomized CATNON trial to validate the clinical relevance of these epigenetic subtypes. METHODS The phase III CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4 Gy radiotherapy +/- concurrent and/or adjuvant TMZ. CNV data and methylation data were derived from Infinium MethylationEPIC arrays. Epigenetic subtyping and risk of progression to G-CIMP low were determined from random forest models and 7 specific CpGs (PMID: 29642018). IDH1/2 status was determined with a glioma-tailored NGS panel. Overall survival (OS) was measured from date of randomization. RESULTS Methylation analysis was performed on 654 tumors: 440 were IDH1/2mt, 204 IDH1/2wt and of 10 IDH1/2 status was unknown; 8 IDH1/2mt were 1p/19q codeleted. Based on methylation, tumors were classified as G-CIMP high (n=409), G-CIMP low (n=19), codel-like (n=18), mesenchymal-like (n=107), classic-like (n=48), and PA-like tumors (n=53). Median OS between these epigenetic subtypes varied considerably: codel-like 9.1 yrs, G-CIMP high 9.5 yrs, G-CIMP low 2.8 yrs, mesenchymal-like 1.3 yrs, classic-like 1.6 yrs, and PA-like 2.8 yrs. The difference in OS of the IDH1/2mt astrocytoma subgroup patients was prominent [G-CIMP low vs G-CIMP high: HR 4.12, 95% CI 2.37-7.19, p < 0.001]. Within the IDH1/2mt G-CIMP high astrocytoma patients, 115 tumors were predicted to have risk of progression to G-CIMP low and patients with such tumors indeed had poorer survival [risk vs no-risk: HR 1.59, 95% CI 1.10-2.31, p = 0.02]. Median OS in G-CIMP high tumors with (n=37) and without (n=366) CDKN2A/B HD was 3.3 yrs versus not reached [p< 0.001], in G-CIMP low tumors it was 1.2 yrs (n=6) versus 4.4 yrs (n=12) [p=0.008]. CONCLUSIONS In IDH1/2mt anaplastic astrocytoma, G-CIMP status and CDKN2A/B HD are of independent prognostic value.

Engrailed 1 overexpression as a potential prognostic marker in Lower Grade Glioma.

BackgroundEngrailed 1 (EN1), as a member of homeobox-containing transcription factors, participates in the development of the brain. High expressions of EN1 exist in various tumors. However, the role of EN1 in lower grade glioma (LGG) is still unknown.MethodsCoefficients of Cox regression were examined by data mining among 13 cancer types using OncoLnc to validate EN1 expressions in LGG patients from The Cancer Genome Atlas database (TCGA). Bioinformatic analysis was performed by using R2 and the UCSC Xena browser based on the data from 273 glioma cases in GSE16011 from GEO datasets and 530 cases of LGG patients in TCGA. Cases in GSE16011 were divided into two groups according to IDH1 mutation status. Cases in TCGA-LGG were classified to subtypes according to histopathological results, IDH1 mutation status and 1p19q status. The Kaplan–Meier survival curves were performed to analyze the relationship between EN1 expressions and clinicopathological characteristics and survival time respectively.ResultsCox regression results showed that LGG was ranked statistically first among 13 different cancer types according to the false discovery rate (FDR) correction. Results from GSE16011 showed that: glioma, LGG and LGG with IDH1 mutation patients with high EN1 expressions had significantly shorter 5, 10, and 15-year overall survival time (OS) (p < 0.001). Similar results from TCGA-LGG showed that LGG patients with high EN1 expressions had significantly shorter 15-year OS, irrespective of IDH1 mutation and 1p19q co-deletion (p < 0.001). The astrocytoma subgroup showed highest levels of EN1 expression and shortest 5, 10 and 15-year OS compared with oligoastrocytoma and oligodendroglioma (p < 0.05).ConclusionEN1 can be used as a prognostic marker in LGG patients, combined with IDH1 mutation and 1p19q co-deletion.

Texture analysis on conventional MRI images accurately predicts early malignant transformation of low-grade gliomas.

Texture analysis performed on MRI images can provide additional quantitative information that is invisible to human assessment. This study aimed to evaluate the feasibility of texture analysis on preoperative conventional MRI images in predicting early malignant transformation from low- to high-grade glioma and compare its utility to histogram analysis alone. A total of 68 patients with low-grade glioma (LGG) were included in this study, 15 of which showed malignant transformation. Patients were randomly divided into training (60%) and testing (40%) sets. Texture analyses were performed to obtain the most discriminant factor (MDF) values for both training and testing data. Receiver operating characteristic (ROC) curve analyses were performed on MDF values and 9 histogram parameters in the training data to obtain cutoff values for determining the correct rates of discrimination between two groups in the testing data. The ROC analyses on MDF values resulted in an area under the curve (AUC) of 0.90 (sensitivity 85%, specificity 84%) for T2w FLAIR, 0.92 (86%, 94%) for ADC, 0.96 (97%, 84%) for T1w, and 0.82 (78%, 75%) for T1w + Gd and correctly discriminated between the two groups in 93%, 100%, 93%, and 92% of cases in testing data, respectively. In the astrocytoma subgroup, AUCs were 0.92 (88%, 83%) for T2w FLAIR and 0.90 (92%, 74%) for T1w + Gd and correctly discriminated two groups in 100% and 92% of cases. The MDF outperformed all 9 of the histogram parameters. Texture analysis on conventional preoperative MRI images can accurately predict early malignant transformation of LGGs, which may guide therapeutic planning. • Texture analysis performed on MRI images can provide additional quantitative information that is invisible to human assessment. • Texture analysis based on conventional preoperative MR images can accurately predict early malignant transformation from low- to high-grade glioma. • Texture analysis is a clinically feasible technique that may provide an alternative and effective way of determining the likelihood of early malignant transformation and help guide therapeutic decisions.

18F-DOPA uptake does not correlate with IDH mutation status and 1p/19q co-deletion in glioma.

The role of amino acid positron emission tomography (PET) in glioma grading and outcome prognostication has not yet been well established. This is particularly true in the context of the new WHO 2016 classification, which introduced a definition of glioma subtypes primarily based on molecular fingerprints. The aim of the present study was to correlate 3,4‑dihydroxy‑6‑[18F]‑fluoro-L‑phenylalanine (F-DOPA) uptake parameters with IDH mutation, 1p/19q status, and survival outcomes in patients with glioma. The study population consisted of 33 patients (17 M/16 F, mean age: 46 ± 13years) who underwent F-DOPA PET/CT for the evaluation of tumor extent before the start of chemo or radiotherapy. The presence of IDH mutation and 1p/19q status was assessed in all the cases. Tumor volume and semiquantitative uptake parameters, namely SUVmax, tumor-to-normal brain ratio and tumor-to-normal striatum ratio, were calculated for each tumor. Imaging-derived parameters were compared between patients stratified according to molecular fingerprints, using parametric or non-parametric tests, where appropriate. The Kaplan-Meier method was used to assess differences of overall survival (OS) and progression-free survival (PFS) between groups. PET parameters were also tested as prognostic factors in univariate Cox survival regression models. There were 12 IDH-wild-type and 21 IDH-mutant patients. Stratification according to 1p/19q co-deletion resulted in 20 non-co-deleted and 13 co-deleted patients. Median follow-up time from PET/CT exam was 30.5months (range 3.5-74months). Semiquantitative uptake parameters did correlate neither with IDH mutation nor with 1p/19q status. Uptake was similar in low-grade and high-grade tumors, respectively. In addition, F-DOPA uptake parameters, macroscopic tumor volume, or tumor grade did not stratify OS, while a correlation between SUVmax and PFS was shown in the subgroup of astrocytomas. On the other hand, IDH mutation status and presence of 1p/19q co-deletion had a significant impact on survival outcomes. The prognostic value of IDH mutation status was also confirmed in the subgroup of patients with astrocytic tumors. F-DOPA uptake parameters do not correlate with tumor molecular and histological characteristics. The predictive value of PET-derived parameters on outcomes of survival is limited.

VRK2 identifies a subgroup of primary high-grade astrocytomas with a better prognosis

BackgroundMalignant astrocytomas are the most common primary brain tumors and one of the most lethal among human cancers despite optimal treatment. Therefore, the characterization of molecular alterations underlying the aggressive behavior of these tumors and the identification of new markers are thus an important step towards a better patient stratification and management.Methods and resultsVRK1 and VRK2 (Vaccinia-related kinase-1, -2) expression, as well as proliferation markers, were determined in a tissue microarray containing 105 primary astrocytoma biopsies. Kaplan Meier and Cox models were used to find clinical and/or molecular parameters related to overall survival. The effects of VRK protein levels on proliferation were determined in astrocytoma cell lines. High levels of both protein kinases, VRK1 or VRK2, correlated with proliferation markers, p63 or ki67. There was no correlation with p53, reflecting the disruption of the VRK-p53-DRAM autoregulatory loop as a consequence of p53 mutations. High VRK2 protein levels identified a subgroup of astrocytomas that had a significant improvement in survival. The potential effect of VRK2 was studied by analyzing the growth characteristics of astrocytoma cell lines with different EGFR/VRK2 protein ratios.ConclusionHigh levels of VRK2 resulted in a lower growth rate suggesting these cells are more indolent. In high-grade astrocytomas, VRK2 expression constitutes a good prognostic marker for patient survival.

Correlation between Cerebral Blood Volume Measurements by Perfusion-Weighted Magnetic Resonance Imaging and Two-Year Progression-Free Survival in Gliomas

Our goal was to determine whether relative cerebral blood volume (rCBV) can serve as an adjunct to histopathologic grading in the assessment of gliomas, with the hypothesis that rCBV can predict two-year survival. We evaluated 29 newly diagnosed gliomas (13 WHO grade II, seven grade III, nine grade IV; 17 astrocytomas, 12 oligodendroglial tumors). Dynamic susceptibility-weighted contrast-enhanced perfusion MR images and CBV maps were obtained. rCBVmax measurements (maximum tumor CBV/contralateral normal tissue CBV) and progression-free survival (PFS) were recorded. Receiver operating characteristic curves and Kaplan-Meier survival curves were calculated for rCBVmax and histologic grade. rCBVmax measurements differed between gliomas without (2.38 +/- 1.22) and with progression (5.57 +/- 2.84) over two years. The optimal rCBVmax cut-off value to predict progression was 2.95. rCBVmax < 2.95 was a significant predictor of two-year PFS, almost as accurate as WHO grade II. In the pure astrocytoma subgroup, the optimal rCBVmax cut-off value to predict progression was 2.85. In this group rCBVmax < 2.85 was a significant predictor of two-year PFS, an even better predictor of two-year PFS than WHO grade II. rCBVmax can be used to predict two-year PFS in patients with gliomas, independent of pathologic findings, especially in tumors without oligodendroglial components.

Intellectual aspects of cognitive performance in children after treatment for medulloblastoma and astrocytoma.

present study investigated the relationship between posterior fossa tumors (astrocytoma and medulloblastoma) and their respective treatments and cognitive performance in Brazilian children by measuring Intelligence Quotient (IQ). Twenty children were enrolled in the study, of whom 13 were diagnosed with astrocytoma (average age at evaluation, 10.2 years; eight girls and five boys) and seven were diagnosed with medulloblastoma (average age at evaluation, 9.2 years; five girls and two boys). The first subgroup underwent exclusively tumor resection surgery, and the second subgroup underwent surgery, chemotherapy (Vincristine, Cisplatine, and Carmustine), and radiotherapy (total dose, 54 Gy). The inclusion criteria for the clinical group were normal social and emotional behavior before the diagnosis and motor and visual performance not excessively deteriorated after surgery. All participants were submitted to the Wechsler Intelligence Scale for Children - third version, and their scores were related to standard norms established for Brazilian children and compared with regard to the diagnosis subgroups and treatment modalities. Statistically significant differences were identified between the two diagnosis subgroups in Performance IQ and Processing Speed scores. The medulloblastoma subgroup presented poorer performance in all domains compared with the astrocytoma subgroup. Time interval between diagnosis and neuropsychological evaluation also had a significant effect on Processing Speed and Freedom from Distractibility in the medulloblastoma subgroup. These results provide empirical evidence of a possible significant effect of radiotherapy exposure on processing speed and global intellectual capacity. Keywords: posterior fossa tumor, radiotherapy, intelligence evaluation.

The familiality of primary brain tumors as studied in the Utah Population Database (UPDB)

1526 Background: The UPDB is a unique database linking 2.5 million Utah individuals with genealogical data to 80,000 Utah SEER cancer registry records since 1973. The familial nature of cancer has been well studied using this resource. Here we use similar techniques to investigate 1550 individuals diagnosed with brain tumors. Methods: We estimated the relative risk of brain cancer in relatives of brain cancer cases using internal age- and sex-specific rates of brain cancer estimated from UPDB. We estimated the average relatedness of brain cancer cases (compared to the average relatedness for 1000 matched control groups) using the Genealogical Index of Familiality measure, which extends beyond first degree relatives and looks at all pair wise relationships between cases. We considered all 1550 brain cancers as a group, the subgroup of 364 astrocytomas and the subgroup of 571 glioblastomas. Results: The relative risk for brain cancer in 1st degree relatives of all brain cancer cases is 2.78 (p=5.1xe-7). The average relatedness of all brain cancers was significantly higher than expected in controls (p=0.03). The relative risk for brain cancer in 1st degree relatives of cases with astrocytoma was 3.03. The astrocytoma subgroup also showed significantly higher average relatedness than controls (p=0.002). The relative risk of all brain cancers in the first-degree relatives of glioblastoma cases was 2.60 (p=2.0xe-3). The glioblastoma subgroup of cases did not show significantly higher average relatedness than expected in controls (p=0.68). Conclusions: The UPDB resource provides strong evidence for a familial component in brain cancer that seems to extend beyond first-degree relatives. The subgroup of astrocytoma showed more evidence for underlying genetic component than the glioblastoma subgroup. Study of high-risk pedigrees could allow increased understanding of brain cancer predisposition genes. No significant financial relationships to disclose.

Increased incidence rates but no space-time clustering of childhood astrocytoma in Sweden, 1973-1992

Incidence patterns, trends, and spatial and/or temporal clustering of childhood brain tumors were analyzed in the population-based national cancer registry of Sweden. Temporal trends were analyzed by a logistic regression procedure in which the average annual percentages of change in incidence rates and the corresponding 95% confidence intervals (CIs) were calculated. Spatial and/or temporal clustering were investigated by using a geographic information system and analyzed with a modified version of the Knox test and a spatial scan statistic. Primary brain tumors in 1223 children ages 0-15 years were registered during 1973-1992. In 80% of cases, the tumor was classified as malignant. Conclusive histopathology was classified in 1142 cases. The age-adjusted incidence rate for all subtypes of brain tumors was 35.9 cases per million children, and for malignant brain tumors 28.6. A statistically significant increasing temporal trend was observed for the group of malignant brain tumors as a whole (P=0.0001) and the astrocytoma subgroup (P=0.0001). The annual average increases were 2.6% (95% CI=1.5-3.8) and 3.0%, respectively (95% CI=1.6-4.4). The increase in astrocytoma cases was significantly larger for girls than for boys (P=0.021) and was most striking for girls ages 6-15 years, with an annual average increase of 4.7%. Rates had not increased for the primitive neuroectodermal tumor (PNET)/medulloblastoma or ependymoma subgroups. The geographic distribution of astrocytoma cases was homogenous. No statistically significant space-time interaction or local clusters in space and/or time were found for astrocytomas only or when astrocytomas were grouped with PNETs/medulloblastomas and ependymomas. The results show statistically increased incidence rates of childhood astroglial tumors, predominantly for girls, in Sweden during the period 1973-1992, but no clustering in space or time.

Increased incidence rates but no space–time clustering of childhood astrocytoma in Sweden, 1973–1992

BACKGROUND Incidence patterns, trends, and spatial and/or temporal clustering of childhood brain tumors were analyzed in the population-based national cancer registry of Sweden. METHODS Temporal trends were analyzed by a logistic regression procedure in which the average annual percentages of change in incidence rates and the corresponding 95% confidence intervals (CIs) were calculated. Spatial and/or temporal clustering were investigated by using a geographic information system and analyzed with a modified version of the Knox test and a spatial scan statistic. RESULTS Primary brain tumors in 1223 children ages 0–15 years were registered during 1973–1992. In 80% of cases, the tumor was classified as malignant. Conclusive histopathology was classified in 1142 cases. The age-adjusted incidence rate for all subtypes of brain tumors was 35.9 cases per million children, and for malignant brain tumors 28.6. A statistically significant increasing temporal trend was observed for the group of malignant brain tumors as a whole (P = 0.0001) and the astrocytoma subgroup (P = 0.0001). The annual average increases were 2.6% (95% CI = 1.5–3.8) and 3.0%, respectively (95% CI = 1.6–4.4). The increase in astrocytoma cases was significantly larger for girls than for boys (P = 0.021) and was most striking for girls ages 6–15 years, with an annual average increase of 4.7%. Rates had not increased for the primitive neuroectodermal tumor (PNET)/medulloblastoma or ependymoma subgroups. The geographic distribution of astrocytoma cases was homogenous. No statistically significant space–time interaction or local clusters in space and/or time were found for astrocytomas only or when astrocytomas were grouped with PNETs/medulloblastomas and ependymomas. CONCLUSIONS The results show statistically increased incidence rates of childhood astroglial tumors, predominantly for girls, in Sweden during the period 1973–1992, but no clustering in space or time. Cancer 1999;85:2077–90. © 1999 American Cancer Society.

Interstitial Irradiation and Hyperthermia for the Treatment of Recurrent Malignant Brain Tumors

Abstract Between June 1987 and June 1989, 29 recurrent malignant gliomas or recurrent solitary brain metastases in 28 patients were treated in a Phase I study of interstitial irradiation and hyperthermia. Patient age ranged from 18 to 65 years, and the Karnofsky Performance Status scores ranged from 40 to 90%. There were 13 glioblastomas, 10 anaplastic astrocytomas. 3 melanomas, and 3 adenocarcinomas. Catheters were implanted stereotactically after computed tomography-based preplanning. Hyperthermia was administered before and after brachytherapy, using one to six 2450- or 915-MHz helical coil microwave antennas and one to three multisensor fiberoptic thermometry probes. The goal was to heat as much of the tumor as possible to 42.5±C for 30 minutes. Within 30 minutes after the first hyperthermia treatment, implant catheters were afterloaded with high-activity iodine-125 seeds delivering tumor doses of 32.6 to 61.0 Gy. Most patients had no sensation of heating. Complications included seizures in 5 patients, reversible neurological changes in 9 patients, a scalp burn in 1, and infections in 3. Of 28 evaluable 2-month follow-up scans, 11 showed definite improvement in the radiological appearance of the tumor, 4 were slightly improved, 7 were stable, and 6 showed tumor progression. Ten patients underwent reoperation for persistent tumor and/or necrosis. Eleven of 28 patients are alive 40 to 97 weeks after treatment. Thirteen patients died of a brain tumor, 2 died of extracranial melanoma metastases, 1 died of new brain melanoma metastases, and 1 died of a pulmonary embolus. The median survival was 55 weeks overall. Median survival has not yet been reached for the anaplastic astrocytoma subgroup. We conclude that interstitial brain hyperthermia using helical coil microwave antennas is technically feasible. The level of toxicity is acceptable, and the computed tomographic response rate is encouraging.

Interstitial irradiation and hyperthermia for the treatment of recurrent malignant brain tumors

Between June 1987 and June 1989, 29 recurrent malignant gliomas or recurrent solitary brain metastases in 28 patients were treated in a Phase I study of interstitial irradiation and hyperthermia. Patient age ranged from 18 to 65 years, and the Karnofsky Performance Status scores ranged from 40 to 90%. There were 13 glioblastomas, 10 anaplastic astrocytomas, 3 melanomas, and 3 adenocarcinomas. Catheters were implanted stereotactically after computed tomography-based preplanning. Hyperthermia was administered before and after brachytherapy, using one to six 2450- or 915-MHz helical coil microwave antennas and one to three multisensor fiberoptic thermometry probes. The goal was to heat as much of the tumor as possible to 42.5 degrees C for 30 minutes. Within 30 minutes after the first hyperthermia treatment, implant catheters were afterloaded with high-activity iodine-125 seeds delivering tumor doses of 32.6 to 61.0 Gy. Most patients had no sensation of heating. Complications included seizures in 5 patients, reversible neurological changes in 9 patients, a scalp burn in 1, and infections in 3. Of 28 evaluable 2-month follow-up scans, 11 showed definite improvement in the radiological appearance of the tumor, 4 were slightly improved, 7 were stable, and 6 showed tumor progression. Ten patients underwent reoperation for persistent tumor and/or necrosis. Eleven of 28 patients are alive 40 to 97 weeks after treatment. Thirteen patients died of a brain tumor, 2 died of extracranial melanoma metastases, 1 died of new brain melanoma metastases, and 1 died of a pulmonary embolus. The median survival was 55 weeks overall. Median survival has not yet been reached for the anaplastic astrocytoma subgroup. We conclude that interstitial brain hyperthermia using helical coil microwave antennas is technically feasible. The level of toxicity is acceptable, and the computed tomographic response rate is encouraging.