Brain Radionecrosis Research Articles

Irradiated Volume as a Predictor of Brain Radionecrosis After Linear Accelerator Stereotactic Radiosurgery

To investigate the correlation between volume of brain irradiated by stereotactic radiosurgery (SRS) and the incidence of symptomatic and asymptomatic brain radionecrosis (RN). A retrospective analysis was performed of patients treated with single-fraction SRS for brain metastases at our institution. Patients with at least 6-month imaging follow-up were included and diagnosed with RN according to a combination of criteria, including appearance on serial imaging and histology. Univariate and multivariate analyses were performed to determine the predictive value of multiple variables, including volume of brain receiving a specific dose (V8 Gy-V18 Gy). Sixty-three patients were reviewed, with a total of 173 lesions. Most patients (63%) had received previous whole-brain irradiation. Mean prescribed SRS dose was 18 Gy. Symptomatic RN was observed in 10% and asymptomatic RN in 4% of lesions treated. Multivariate regression analysis showed V8 Gy-V16 Gy to be most predictive of symptomatic RN (p < 0.0001). Threshold volumes for significant rise in RN rates occurred between the 75th and 90th percentiles, with a midpoint volume of 10.45 cm(3) for V10 Gy and 7.85 cm(3) for V12 Gy. Analysis of patient and treatment variables revealed V8 Gy-V16 Gy to be the best predictors for RN using linear accelerator-based single-fraction SRS for brain metastases. We propose that patients with V10 Gy >10.5 cm(3) or V12 Gy >7.9 cm(3) be considered for hypofractionated rather than single-fraction treatment, to minimize the risk of symptomatic RN.

Hyperbaric oxygen therapy for radiation‐induced brain necrosis in a patient with primary central nervous system lymphoma

A 45-year-old man who developed brain radionecrosis in the right frontal and left temporoparietal lobes after receiving whole brain radiotherapy and stereotactic radiosurgery for primary central nervous system lymphoma. Since high dose steroid treatment failed and he declined to undergo surgery, he was referred to hyperbaric oxygen (HBO) therapy. Both clinical and radiological findings improved after HBO therapy. Steroid requirements were also reduced. HBO therapy may have a potential value in treatment of brain radionecrosis.

Dosimetry study of a phase II multiple-dose intracavitary administration of 131I-TM601 in adult patients with recurrent high-grade glioma

e13006 Background: Postoperative radiotherapy for glioma has been shown to improve survival with increased radiation doses. Dose escalation of external beam radiotherapy or brachytherapy is limited by normal brain radionecrosis. Radiolabeled targeting molecules can deliver localized radiation to tumor and reduce normal brain radionecrosis. TM601, or synthetic Chlorotoxin, is a peptide derived from scorpion venom that specifically binds to tumor cells. Here we report dosimetry results of an imaging sub-study of a phase II trial, in which weekly doses of 131I-TM601 were infused into surgically created tumor resection cavities for 3 or 6 weeks. Methods: Five out of 76 patients treated in a phase II trial were imaged after receiving 1, 3, or 6 doses of 40 mCi/0.8 mg 131I-TM601 intracavitarily. For each imaging study, 5 sequential SPECT images (1–168 hour) were registered with MRI to determine the 131I-TM601 radiation dose to the 2-cm tumor cavity margin. Five sequential body scans were also acquired to determine 131I-TM601 radiation dose to extra-cranial organs. Results: 131I-TM601 is a rapidly penetrating and clearing radiolabeled peptide. The median residual activity in the cavity at 7 days post injection was 8.4%. Median radiation dose to the cavity margin was 121 cGy/mCi and ranged 52- 338 cGy/mCi in 5 subjects. The median coefficient of variation (intra-patient inter-fraction) for the 2-cm margin dose was 14.7% and ranged 7.1–18.9%. Median tumor cavity volume was 11.4 mL, and ranged 5.2 - 35.5 mL. There was no observed correlation between the 2-cm margin dose and the cavity volume. Median radiation dose to thyroid, kidneys, red marrow, and body was 8.3, 1.3, 0.4, and 0.6 cGy/mCi, respectively. Conclusions: Radiation dose ratio for 2-cm cavity margin-to-normal tissues was quite high. While intra-patient reproducibility was relatively good, cumulative effect of the residual activity was only meaningful within a week. These results support the multi-dose fractionation scheme for 131I-TM601 to minimize normal tissue toxicity, including radiation necrosis, and extend continuous irradiation to clinical or sub-clinical residual tumor cells after surgery. [Table: see text]

Irradiated Volume as a Predictor of Brain Radionecrosis after LINAC Stereotactic Radiosurgery

Stereotactic radiosurgery (SRS) is a widely-used tool for the treatment of metastatic brain tumors. The most important late toxicity of SRS is brain radionecrosis (RN), but there is relatively little data regarding predictive factors for the development of necrosis. This retrospective review investigates the correlation between the volume of brain irradiated at a given dose and the incidence of symptomatic (SRN) and asymptomatic radionecrosis (ARN).

Radionécrose cérébrale chez les patients irradiés pour cancer du nasopharynx : à propos de neuf cas

Purpose To study the clinical, radiological, therapeutic and progressive aspects of brain radionecrosis after treatment for nasopharyngeal carcinoma. Patients and methods Nine patients (seven men and two women) of mean age 47.7 years old (extremes: 18–57 years old) were treated for UCNT (undifferentiated carcinoma of the nasopharynx) between 1989 and 2003 and developed cerebral radionecrosis. All patients were treated with radical radiotherapy. The mean total dose was 73.5 Gy (70–75 Gy). Dose per fraction was 2 to 2.5 Gy, one fraction daily. One patient received adjuvant brachytherapy to the dose of 8 Gy and four patients also received chemotherapy. Results Brain radionecrosis was authenticated by brain imaging (CT scan ± MRI): the imaging was ordered in seven cases to elucidate non-specific neurological signs and two cases were discovered fortuitously. The time to the appearance of neurological signs was 40.3 months (10 to 108 months). The localization was temporal in six cases, parieto-occipital (one case) and bulbomedullar (two cases). After a mean follow-up period of 30.6 months (12–84 months), clinical outcomes were favorable in all cases receiving medical treatment (corticoids), with a stabilization of the radiological lesions in eight cases and complete radiological regression in one patient. Conclusion Brain radionecrosis is a late complication rarely occurring in patients irradiated for UCNT. Imaging techniques (CT scan but more so MRI) play a major role in the diagnosis. Corticotherapy resulted in a durable objective response in all patients and, in most cases, resulted in radiological stabilization.

Results of three-dimensional stereotactically-guided radiotherapy in recurrent medulloblastoma.

To evaluate survival rates and side effects after stereotactically-guided radiotherapy (SRT) in patients with recurrent medulloblastoma of the brain. Between 1992 and 2000, 20 patients with 29 radiological manifestations were treated with fractionated SRT (n = 21) or radiosurgery (n = 8). Median age was 16 years with 6 patients < or = 14 years. All patients had prior cranio-spinal radiotherapy plus boost to the posterior fossa with a total dose of 54 Gy. Time to recurrence was 33 months mean. Eighteen of the 29 lesions were located within the boost volume. Chemotherapy was given according to current international study protocols (HIT) in all patients. Mean total dose for re-irradiation was 24 Gy for fractionated stereotactically-guided radiotherapy, and 15 Gy for radiosurgery. Mean follow-up was 88.5 months. Overall local control was 89.7%. Thirteen recurrences showed partial or complete response in CT/MR-imaging, 13 showed stable disease. Local tumor progression was seen 5 months mean after radiotherapy in three cases. A multifocal intracranial progression was seen in 9 patients, 5 patients developed additional spinal metastases. Thirteen patients died with disseminated cranio-spinal progression, after 72.6 months median. No late toxicity > CTC II(o) especially no brain radionecrosis was seen after radiotherapy. SRT is effective and safe in the treatment of recurrent medulloblastoma to improve local control without evident side effects. The main problem remains the control of subclinical cranio-spinal dissemination.

Fractionated stereotactically guided radiotherapy and radiosurgery in the treatment of functional and nonfunctional adenomas of the pituitary gland

Purpose: We evaluated survival rates and side effects after fractionated stereotactically guided radiotherapy (SCRT) and radiosurgery in patients with pituitary adenoma. Methods and Materials: Between 1989 and 1998, 68 patients were treated with FSRT ( n = 63) or radiosurgery ( n = 5) for pituitary adenomas. Twenty-six had functional and 42 had nonfunctional adenomas. Follow-up included CT/MRI, endocrinologic, and ophthalmologic examinations. Mean follow-up was 38.7 months. Seven patients received radiotherapy as primary treatment and 39 patients received it postoperatively for residual disease. Twenty-two patients were treated for recurrent disease after surgery. Mean total dose was 52.2 Gy for SCRT, and 15 Gy for radiosurgery. Results: Overall local tumor control was 93% (60/65 patients). Forty-three patients had stable disease based on CT/MRI, while 15 had a reduction of tumor volume. After FSRT, 26% with a functional adenoma had a complete remission and 19% had a reduction of hormonal overproduction after 34 months’ mean. Two patients with STH-secreting adenomas had an endocrinologic recurrence, one with an ACTH-secreting adenoma radiologic recurrence, within 54 months. Reduction of visual acuity was seen in 4 patients and partial hypopituitarism in 3 patients. None of the patients developed brain radionecrosis or radiation-induced gliomas. Conclusion: Stereotactically guided radiotherapy is effective and safe in the treatment of pituitary adenomas to improve local control and reduce hormonal overproduction.

Prognostic factors and results of therapy for adult thalamic and brainstem tumors.

This report is a retrospective analysis of 83 adults (greater than 16 years of age) with histologically proven or presumed primary neoplasms of the thalamus, hypothalamus, midbrain, pons, and medulla. Patients were treated with combined surgery and postoperative irradiation or with irradiation alone at the Washington University Medical Center (St. Louis, MO) from January 1950 through December 1984. Histologic analysis confirmed the diagnosis of tumor in 21, including nine with well-differentiated astrocytoma, four with astrocytoma with anaplasia, and eight with glioblastoma multiforme. Overall and disease-free survivals at 5 years were 28.7 and 23.2%, respectively. A statistical analysis was performed to ascertain the prognostic importance of the following variables: age, race, gender, duration of symptoms, cranial nerve paresis, primary site, extent of surgery, histology, and irradiation dose. The only factor identified by univariate analysis to be critical for survival was primary location of disease. Patients with supratentorial (thalamus/hypothalamus, midbrain) tumors had a 10-year disease-free survival of 15.4% compared to 29.6% for those with infratentorial (pons, medulla) tumors (P = 0.07). Patients with lesions of the pons had a 5-year disease-free survival of 35.8% compared to 13.8% for those with tumors of the thalamus (P = 0.05). Increasing irradiation dose was not correlated with superior survival. Factors evaluated but established to be insignificant were age (P = 0.27), race (P = 0.63), gender (P = 0.27), duration of symptoms (P = 0.19), cranial nerve paresis (P = 0.71), histologic type (P = 0.16), and extent of surgery (P = 0.94). Follow-up for 13 surviving patients ranged from 2.6 to 28.7 (mean, 12.0) years. Neurologic deficits in surviving patients were absent in 15% (two of 13), mild in 62% (eight of 23), and moderate in 23% (three of 13). One case of brain radionecrosis was identified (6000 cGy, 200 cGy daily).

Prognostic factors and results of surgery and postoperative irradiation in the management of pituitary adenomas

Prognostic factors and results of therapy were analyzed in a retrospective examination of 121 patients with pituitary adenomas treated with surgery and postoperative irradiation (RT) from January 1954 through December 1982 at the Radiation Oncology Center, Mallinckrodt Institute of Radiology. The 10-year overall and disease-free survival for all patients was 85.1 and 89.4%. The expected survival for an age-, gender-, and race-matched population was not significantly distinct at 85.3% ( p = 0.72). Follow-up of 94 surviving patients ranged from 3.4 to 29.5 years (mean, 11.7). Statistical analysis was performed for multiple prognostic factors including age, race, gender, disease bulk, visual field symptoms, disease type, surgical approach, and irradiation dose and volume. The only prognostic variable identified by univariate analysis to significantly alter disease-free survival was irradiation dose. Patients receiving 5000–5400 cGy had a tumor control rate of 94.1% ( 64 68 ) compared to 85.0% ( 17 20 ) for 4000–4999 cGy, 75.0% ( 18 24 ) for 3000–3999 cGy, and 28.6% ( 2 7 ) for<3000 cGy ( p = 0.000059). Factors evaluated but established to be insignificant were age, race, gender, disease bulk, visual field symptoms, disease type, surgical approach, and irradiated volume. The 10-year disease-free survival by classification was 93.3% for patients with amenorrhea/galactorrhea, 89.9% for non-functioning adenomas, and 76.4% for acromegaly ( p = 0.21). Overall improvement in visual field defects subsequent to treatment occurred in 48.4% ( 44 91 ) of those with visual field defects before RT and was significantly correlated with RT dose. The median time to progression of disease was 10.2 years with the last failure occurring at 25 years following the fulfillment of RT. Severe complications related to RT were apparent in 1.7% ( 2 121 ). None were known to have endured brain radionecrosis. Serious surgical complications occurred in 9.9% ( 12 121 ).

Multifocal brain radionecrosis masquerading as tumor dissemination

The authors report on an autopsy-proven case of multifocal widespread radionecrosis involving both cerebral hemispheres and masquerading as tumor dissemination on a CT scan done 13 months after complete resection of an oligodendroglioma followed by radiation therapy. This case demonstrates that radiation damage may be present in a CT scan as a multifocal, disseminated lesion. Since the survival of brain-tumor patients who have undergone radiation therapy is prolonged by aggressive therapy, the incidence and variability of radiation-induced complications in such cases is likely to increase. For similar reasons, the radionecrosis in such cases should be taken into consideration. A short review of the CT scan findings and diagnostic and therapeutic considerations in a case of widespread radionecrosis is presented. The need for appropriate diagnosis and subsequent life-saving management is emphasized.

Cerebral radionecrosis: Incidence and risk in relation to dose, time, fractionation and volume

The authors irradiated 152 patients with primary brain and pituitary tumors from 1974 to 1976. Seven of 139 patients (5%) who received 4500 rad or greater using 180 to 200 rad fractions, developed pathologically documented cerebral radionecrosis within a median time of 14 months after completion of irradiation. The necrosis was documented by autopsy in four patients, at reoperation in two and after needle biopsy in one. It was located in the brain, distant from the original tumor in three patients, adjacent to tumor in two, and within the tumor bed in two. The latter two were classified as radionecrosis because one patient died with only minimal tumor remaining and the other patient deteriorated neurologically and stabilized after removal of the necrotic mass. On clinical grounds, we suspect that two additional patients had radiation damage to the brain, because they deteriorated neurologically without neuroradiologic evidence of tumor. Study of computerized tomography (CT) scans and superimposed dose distributions showed that necrosis was mot always within the zone of highest dose (3 patients). Risk of radionecrosis was greatest in the upper regions of dose but could not be associated with shorter time, larger fractions, or larger field size. Pathologically documented radionecrosis of brain did not develop below doses that were biologically equivalent to 5400 rad in 30 fractions over 42 days.

(Richmond, Virginia)

Journal Article A Study in Chronic Brain Radionecrosis Get access R. H. Brownson, Ph.D., R. H. Brownson, Ph.D. Richmond, Virginia Search for other works by this author on: Oxford Academic PubMed Google Scholar W. M. Shanklin, Ph.D., W. M. Shanklin, Ph.D. Richmond, Virginia Search for other works by this author on: Oxford Academic PubMed Google Scholar D. B. Suter, Ph.D. D. B. Suter, Ph.D. Richmond, Virginia Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Neuropathology & Experimental Neurology, Volume 23, Issue 4, October 1964, Pages 660–675, https://doi.org/10.1097/00005072-196410000-00006 Published: 01 October 1964