Radiation-induced Brain Tumors Research Articles

NCMP-27. CHARACTERISTICS OF RADIATION-INDUCED BRAIN TUMORS AFTER CRANIAL IRRADIATION

Abstract INTRODUCTION The use of radiation therapy (RT) improves the outcome of cancer patients, while additionally increasing the risk of radiation-induced neoplasms in cancer survivors. The most common radiation-induced brain tumors (RIBT) are gliomas (RIG), meningiomas (RIM), and sarcomas (RIS). To investigate the characteristics of RIBT, we reviewed our case series and all relevant cases from the literature review. METHODS From our case series and literature review, we identified 920 RIBT patients who received cranial irradiation. We analyzed the age at irradiation for primary disease. The latency period from irradiation to the development of each RIBT and the median overall survival (OS) of RIBT were analyzed with Kaplan–Meier method. RESULTS Among RIBT patients, 23.2 % were irradiated less than 5 years, and 41.6% were irradiated in the first decade. The median age (interquartile range) at cranial irradiation were 9 (4.35 - 16) years in RIM patients, 9 (5 - 23) years in RIG patients, and 27 (13.7 - 40) years in RIS patients. The latency periods from irradiation to the development of RIM was significantly longer than RIG and RIS (RIM: 21 years, RIG: 9 years, RIS: 10 years; p < 0.0001). The median OS was significantly longer in patients with RIM than in those with RIG and RIS (RIM: not reached, RIG: 11 months, RIS 11 months; p < 0.0001). CONCLUSIONS RIG and RIS had a poor prognosis, while RIM had a relatively better prognosis. Because RIBTs develop more than a decade after cranial irradiation, long-term follow-up is crucial.

Differentiating Radiation Necrosis from Brain Tumor Using Hyperpolarized Carbon-13 MR Metabolic Imaging.

Differentiation between radiation-induced necrosis and tumor recurrence is crucial to determine proper management strategies but continues to be one of the central challenges in neuro-oncology. We hypothesized that hyperpolarized 13C MRI, a unique technique to measure real-time in vivo metabolism, would distinguish radiation necrosis from tumor on the basis of cell-intrinsic metabolic differences. The purpose of this study was to explore the feasibility of using hyperpolarized [1-13C]pyruvate for differentiating radiation necrosis from brain tumors. Radiation necrosis was initiated by employing a CT-guided 80-Gy single-dose irradiation of a half cerebrum in mice (n = 7). Intracerebral tumor was modeled with two orthotopic mouse models: GL261 glioma (n = 6) and Lewis lung carcinoma (LLC) metastasis (n = 7). 13C 3D MR spectroscopic imaging data were acquired following hyperpolarized [1-13C]pyruvate injection approximately 89 and 14days after treatment for irradiated and tumor-bearing mice, respectively. The ratio of lactate to pyruvate (Lac/Pyr), normalized lactate, and pyruvate in contrast-enhancing lesion was compared between the radiation-induced necrosis and brain tumors. Histopathological analysis was performed from resected brains. Conventional MRI exhibited typical radiographic features of radiation necrosis and brain tumor with large areas of contrast enhancement and T2 hyperintensity in all animals. Normalized lactate in radiation necrosis (0.10) was significantly lower than that in glioma (0.26, P =.004) and LLC metastatic tissue (0.25, P =.00007). Similarly, Lac/Pyr in radiation necrosis (0.18) was significantly lower than that in glioma (0.55, P =.00008) and LLC metastasis (0.46, P =.000008). These results were consistent with histological findings where tumor-bearing brains were highly cellular, while irradiated brains exhibited pathological markers consistent with reparative changes from radiation necrosis. Hyperpolarized 13C MR metabolic imaging of pyruvate is a noninvasive imaging method that differentiates between radiation necrosis and brain tumors, providing a groundwork for further clinical investigation and translation for the improved management of patients with brain tumors.

RONC-18. ANALYSIS OF BRAIN TUMOR INDUCED BY IRRADIATION IN CHILDHOOD - A SINGLE INSTITUTIONAL ANALYSIS

BACKGROUNDRadiation-induced brain tumors are rare tumors that appear during long-term follow-up after radiation therapy. Children are at greater risk for radiation -induced brain tumors than adults. The clinical characteristics of radiation-induced brain tumor treated at our hospital were retrospectively examined.PATIENTS AND METHODSClinical characteristics of seven radiation-induced brain tumors that developed in 6 patients irradiated in their childhood at our hospital were analyzed. The background disease, age at irradiation, irradiation dose, period from irradiation to onset, pathological diagnosis, and treatment for radiation-induced brain tumor were examined.RESULTSBackground diseases for irradiation were leukemia in 3 patients, germinoma in 2, medulloblastoma in 1, and the average cranial irradiation dose was 23.2 Gy. The patients tended to be young at irradiation (2–17 yeays; median:4 years old). The time between irradiation and the onset of radiation-induced brain tumors ranged from 9.5 to 39.1 years (median:28 years). Radiation-induced brain tumors comprised 6 meningioma（grade I:5, grade II:1）and 1 high-grade gliomas. All patients underwent surgical removal of the radiation-induced brain tumors and 2 received additional irradiation. During a median of 5.3 years of follow-up after the diagnosis of radiation-induced brain tumors, 2 underwent second surgery, while the remaining 4 have no recurrence. DISCUSSION: In most cases, radiation-induced brain tumors occur for a long time after irradiation in childhood. Monitoring of radiation-induced brain tumors as well as primary tumor recurrence was considered important.

Atypical teratoid rhabdoid tumor located in the pineal region following prophylactic irradiation for acute lymphoblastic leukemia

Atypical teratoid rhabdoid tumor (AT/RT) is a rare entity. In the central nervous system, AT/RT generally arises from the posterior fossa of infants and behaves aggressively. AT/RT is reported to arise from the infratentorial region (63%) and other sites, such as the suprasellar region, cerebellopontine angle, and spinal cord. The pineal region is rare (6%) as a site of origin. Radiation-induced brain tumors are well known. In this report, we present a case of a pineal region tumor causing acute hydrocephalus that could be pathologically diagnosed as AT/RT following prophylactic cranial irradiation for acute lymphoblastic leukemia.

Anaplastic oligodendrogliomas after treatment of acute lymphoblastic leukemia in children

Radiation-induced brain tumors are suggested to be the late complication of acute lymphoblastic leukemia (ALL) treatment. High-grade gliomas, meningiomas, and sarcomas are the most frequent neoplasms. Secondary anaplastic oligodendrogliomas are exceedingly rare. Five cases of pure anaplastic oligodendroglioma have been reported in the literature, and only 1 case was in a child after ALL treatment. The authors present 2 cases of pediatric anaplastic oligodendroglioma after treatment of ALL. Furthermore, they performed a molecular cytogenetic study and found loss of 1p in both cases. The authors provide a review of the previous cases and discuss their findings.

High-grade gliomas in survivors of childhood acute lymphoblastic leukaemia

Dear Editor: We read with great interest the recent article by Bien et al. on high-grade gliomas that occurred in children cured of acute lymphoblastic leukaemia (ALL). In this study, the authors reported two cases of glioblastoma multiforme and one case of anaplastic astrocytoma with poor overall survival despite aggressive treatment. Cranial irradiation has been considered as the most important factor for the development of secondary brain tumours. The authors concluded that early detection followed by complete resection and chemoradiotherapy is of paramount importance; however, they do not warrant better prognosis [1]. We recently studied the secondary malignant brain tumours in children who were previously treated for ALL in our institute and we encountered one case of glioblastoma multiforme and two cases of anaplastic oligodendrogliomas. The tumours developed after a mean period of 6.8 years after ALL treatment. The occurrence of anaplastic oligodendrogliomas is exceedingly rare and only eight cases have been reported in the literature. For further investigation, we undertook a molecular cytogenetic study of the oligodendroglioma specimens obtained from the two patients using fluorescence in situ hybridization (FISH) with DNA probes mapping to chromosome 1p36, 19p13 and 19q13. FISH analysis demonstrated in both cases 1p36 deletions (unpublished data). Studies of oligodendroglioma patients indicated that a loss of chromosome 1p and 19q was associated with high sensitivity to chemotherapy and radiotherapy and a better probability of survival [2]. We believe that it would be interesting to investigate if the allelic loss differs from those observed in primary lesions. Further research is needed to clarify if certain underlying genetic characteristics may also be associated with an increased risk of radiation-induced brain tumours.

Cancer: Strong Signal for Cell Phone Effects

Cancer: Strong Signal for Cell Phone Effects

Radiation-induced brain tumours after central nervous system irradiation in childhood: a review

Radiation-induced cerebral tumours constitute a significant risk for subjects undergoing radiotherapy for the management of cerebral neoplasms. Age-related cerebral vulnerability could be a specific factor in the genesis of these complications. The pertinent literature of both paediatric and adult series has been reviewed. Three personal cases were added. One hundred forty-two paediatric second brain tumours were evaluated. Out of them, 69 were malignant gliomas, 33 meningiomas, 8 sarcomatous lesions and 13 low-grade astrocytomas. The average latency period for the appearance of the second tumour was 8 years. Among the second tumours occurring in adults, meningioma is the most common. In this subgroup, the latency period ranged between 16 and 30 years. Paediatric radiation-induced brain tumours differ from the adult counterpart for both the histological subtypes. These figures indicate a specific vulnerability of the infantile brain demonstrated by the most frequent occurrence of highly malignant lesions.

Thiopurine methyltransferase Genotype Is Not a Risk Factor for Secondary Malignant Neoplasias after Treatment for Childhood Acute Lymphoblastic Leukemia on Berlin-Frankfurt-Muenster Protocols.

The thiopurines mercaptopurine and thioguanine are important components of contemporary polychemotherapeutic treatment protocols for acute leukemias. Thiopurines are prodrugs that undergo intestinal and hepatic metabolism. Activation occurs via a multistep pathway to form thioguanine nucleotides, which are thought to be the major cytotoxic compound through triggering cell cycle arrest and apoptosis. This process is in competition with direct inactivation of thiopurines or their metabolites by thiopurine S-methyltransferase (TPMT). TPMT is a cytosolic enzyme that is ubiquitously expressed in the human body and catalyzes the S-methylation of thiopurines. The TPMT locus is subject to genetic polymorphism, with heterozygous individuals (5 to 11% of Caucasians) having intermediate TPMT activity, and homozygous individuals (0.3 to 0.5% of Caucasians) having low TPMT activity. At least 20 variant TPMT alleles (*2 to *18) have been described so far that confer decreased enzyme activities compared to the TPMT*1 wild-type allele. TPMT genotype is highly concordant with TPMT phenotype. With regard to long-term adverse effects, patients who have diminished TPMT activity were shown to be at increased risk of developing chemotherapy-induced acute myeloid leukemia and radiation-induced second brain tumors tumors after exposure towards mercaptopurine during therapy for childhood acute lymphoblastic leukemia (ALL). To investigate if such an association is generalizable to other entities of secondary malignant neoplasms (SMN) and different treatment approaches for ALL, we collected specimens of 72 patients who developed a SMN after ALL treatment on Berlin-Frankfurt-Muenster (BFM) protocols, analyzed their TPMT genotype and compared genotype frequencies to these in the general ALL patient population. The 72 patient cohort consisted of 49 hematological SMN (half of them received cranial irradiation), 12 brain tumors, and 11 other solid SMN. Neither in the entire patient group nor in subgroup analyses, differences in allele frequencies of TPMT variants conferring diminished enzyme activity were detectable when comparing SMN patients to the overall ALL patient population. Thus, low TPMT activity does not seem to play a major role in the etiology of SMN after treatment for childhood ALL according to BFM treatment strategies. Factors potentially helpful for the explanation of the previously described relationsship of TPMT activity with SMN will be presented.

Radiation-induced brain tumours in nevoid basal cell carcinoma syndrome: implications for treatment and surveillance

We report two cases of radiation-induced intracranial tumours after treatment for medulloblastoma presenting in children with nevoid basal cell carcinoma syndrome. These cases illustrate the need for judicious use of post-operative radiotherapy as secondary tumors are commonly reported. This is particularly important as the initial tumour in this cohort is of the 'less aggressive' desmoplastic subtype.

Long-Term Follow-up for Brain Tumor Development after Childhood Exposure to Ionizing Radiation for Tinea Capitis

Ionizing radiation is an established risk factor for brain tumors, yet quantitative information on the long-term risk of different types of brain tumors is sparse. Our aims were to assess the risk of radiation-induced malignant brain tumors and benign meningiomas after childhood exposure and to investigate the role of potential modifiers of that risk. The study population included 10,834 individuals who were treated for tinea capitis with X rays in the 1950s and two matched nonirradiated groups, comprising population and sibling comparison groups. The mean estimated radiation dose to the brain was 1.5 Gy. Survival analysis using Poisson regression was performed to estimate the excess relative and absolute risks (ERR, EAR) for brain tumors. After a median follow-up of 40 years, an ERR/Gy of 4.63 and 1.98 (95% CI = 2.43-9.12 and 0.73-4.69) and an EAR/Gy per 10(4) PY of 0.48 and 0.31 (95% CI = 0.28-0.73 and 0.12-0.53) were observed for benign meningiomas and malignant brain tumors, respectively. The risk of both types of tumors was positively associated with dose. The estimated ERR/Gy for malignant brain tumors decreased with increasing age at irradiation from 3.56 to 0.47 (P = 0.037), while no trend with age was seen for benign meningiomas. The ERR for both types of tumor remains elevated at 30-plus years after exposure.

25 invited Radiation induced brain tumours. Anecdotal reports or ral risk? Evidence from pituitary radiotherapy

25 invited Radiation induced brain tumours. Anecdotal reports or ral risk? Evidence from pituitary radiotherapy

Radiation-induced brain tumours: potential late complications of radiation therapy for brain tumours.

The development of neoplasms subsequent to therapeutic cranial irradiation is a rare but serious and potentially fatal complication. In this study, we retrospectively reviewed the clinical and pathological aspects of 11 patients who underwent cranial irradiation (range, 24-110 cGy) to treat their primary disease and thereafter developed secondary tumours within a span of 13 years. All tumours arose within the previous radiation fields, and satisfied the widely used criteria for the definition of radiation-induced neoplasms. There was no sex predominance (M: 5, F: 6) and the patients tended to be young at irradiation (1.3-42 years; median age: 22 years). The median latency period before the detection of the secondary tumour was 14.5 years (range: 6.5-24 years). Meningiomas developed in 5 patients, sarcomas in 4, and malignant gliomas in 2. A pre-operative diagnosis of a secondary tumour was correctly obtained in 10 patients based on the neuro-imaging as well as nuclear medicine findings. All patients underwent a surgical removal of the secondary tumour, 3 underwent additional chemotherapy, and one received stereotactic secondary irradiation therapy. During a median of 2 years of follow-up review after the diagnosis of a secondary tumour, 3 patients died related to the secondary tumours (2 sarcomas, 1 glioblastoma), one died of a recurrent primary glioma, while the remaining 7 have been alive for from 10 months to 12 years after being treated for the secondary tumours (median: 3 years). Based on these data, the clinicopathological characteristics and possible role of treatment for secondary tumours are briefly discussed.

Experimental simulation of proton space radiation environments: A dosimetric perspective

Three-dimensional dose calculation techniques developed for radiotherapy treatment planning were used to calculate dose distributions from unidirectional, planar rotational and omnidirectional incident radiation (experimental proton beams and solar flares). The calculations predicted regions of high dose within primate heads exposed to 55-MeV protons, supporting the postulate of radiation-induced brain tumors within this population/1/. Comparisons among predicted doses to the human head from solar flares of three different energies demonstrated differences between unidirectional and omnidirectional irradiation in the space environment. The results can be used to estimate dose distributions based on a) limited phantom measurements, or b) nonuniformly incident radiation in orbit; both situations are difficult to replicate under laboratory exposure conditions.