A Prospective Registry Study of 68Ga-DOTATATE PET/CT Incorporation Into Treatment Planning of Intracranial Meningiomas.

PURPOSE: The current standard for meningioma treatment planning involves magnetic resonance imaging-based guidance. Somatostatin receptor ligands such as 68Ga-DOTATATE are being explored for meningioma treatment planning due to near-universal expression of somatostatin receptors 1 and 2 in meningioma tissue. We hypothesized that 68Ga-DOTATATE positron emission tomography (PET)-guided treatment management for patients with meningiomas is safe and effective and can identify which patients benefit most from adjuvant radiation therapy. METHODS AND MATERIALS: A single-institution prospective registry study was created for inclusion of patients with intracranial meningiomas who received a 68Ga-DOTATATE PET/CT to assist with radiation oncologist decision making. Patients who received a PET scan from January 1, 2018, to February 25, 2022, were eligible for inclusion. RESULTS: Of the 60 patients included, 40%, 47%, and 5% had World Health Organization grades 1, 2, and 3 meningiomas, respectively, and 8% (5 patients) had no grade assigned. According to Radiation Therapy Oncology Group 0539 criteria, 22%, 72%, and 7% were categorized as high, intermediate, and low risk, respectively. After completing their PET scans, 48 patients, 11 patients, and 1 patient proceeded with radiation therapy, observation, and redo craniotomy, respectively. The median follow-up for the entire cohort was 19.5 months. Of the 3 patients (5%) who experienced local failure between 9.2 and 28.5 months after diagnosis, 2 had PET-avid disease in their postoperative cavity and elected for observation before recurrence, and 1 high-risk patient with multifocal disease experienced local failure 2 years after a second radiation course and multiple previous recurrences. Notably, 5 patients did not have any local PET uptake and were observed; none of these patients experienced recurrence. Only 1 grade 3 toxicity was attributed to PET-guided radiation. CONCLUSIONS: This study examined one of the largest known populations of patients with intracranial meningiomas followed by physicians who used 68Ga-DOTATATE PET-guided therapy. Incorporating 68Ga-DOTATATE PET into future trials may assist with clinician decision making and improve patient outcomes.

Incidental Meningioma With Altered PSMA Expression After Systemic Hormone Therapy and Local Radiotherapy Detected by 68 Ga-PSMA PET/CT.

ABSTRACT: A 59-year-old man underwent radical prostatectomy for adenocarcinoma in 2009. Because of the progression of PSA levels, a 68 Ga-PSMA PET/CT scan was performed in January 2020. A suspicious uptake was detected in the left cerebellar hemisphere, and there was no evidence of distant metastatic disease other than recurrent malignancy in the prostatectomy bed. MRI revealed a meningioma located in the left cerebellopontine angle. Although PSMA uptake of the lesion increased in the first imaging after hormone therapy, partial regression was noted after radiotherapy applied to this region.

Occurrence of pituitary hormone deficits in relation to both pituitary and hypothalamic doses after radiotherapy for skull base meningioma.

CONTEXT: Little accurate information is available regarding the risk of hypopituitarism after irradiation of skull base meningiomas. DESIGN: Retrospective study in a single centre. PATIENTS: 48 patients with a skull base meningioma and normal pituitary function at diagnosis, treated with radiotherapy (RXT) between 1998 and 2017 (median follow-up of 90 months). MEASUREMENTS: The GH, TSH, LH/FSH and ACTH hormonal axes were evaluated yearly for the entire follow-up period. Mean doses delivered to the pituitary gland (PitD) and the hypothalamus (HypoD) were calculated, as well as the doses responsible for the development of deficits in 50% of patients after 5 years (TD50). RESULTS: At least one hormone deficit was observed in 38% of irradiated patients and complete hypopituitarism in 13%. The GH (35%), TSH (32%) and LH/FSH axes (28%) were the most frequently affected, while ACTH secretion axis was less altered (13%). The risk of hypopituitarism was independently related to planning target volume (PTV) and to the PitD (threshold dose 45 Gy; TD50 between 50 and 54 Gy). In this series, the risk was less influenced by the HypoD, increasing steadily between doses of 15 and 70 Gy with no clear-cut dose threshold. CONCLUSIONS: Over a median follow-up period of 7.5 years, hypopituitarism occurred in more than one third of patients irradiated for a skull base meningioma, and this prevalence was time- and dose-dependent. In this setting, the risk of developing hypopituitarism was mainly determined by the irradiated target volume and by the dose delivered to the pituitary gland.

Brachytherapy for meningiomas.

Interstitial intracranial radiotherapy implants, or brachytherapy, is an adjuvant option for treatment of recurrent high-grade meningiomas after resection. The implants are placed in the resection cavity following tumor resection. The most commonly used isotope is Iodine-125 (I-125). While there are no controlled studies comparing treatment of meningiomas with or without brachytherapy, several case series report good long-term survival, suggesting that this may be a useful adjuvant for recurrent high-grade tumors. Complications can occur including radiation necrosis, impaired wound healing, hydrocephalus and infection. In the future, new isotopes are being explored that may have fewer complications and better safety profiles.

Brachytherapy as an Adjuvant for Recurrent Atypical and Malignant Meningiomas.

BACKGROUND: Recurrent atypical and malignant meningiomas have poor outcomes with surgical therapy alone. Neither adjuvant chemotherapy nor postoperative radiation therapy remedies this problem. OBJECTIVE: To evaluate our experience with the treatment of 15 patients treated with I-125 or Cs-131 brachytherapy radiation seeds as an adjuvant in these difficult cases. METHODS: Patients with high-grade recurrent meningioma who underwent resection and intraoperative placement of brachytherapy seeds at our institution from 2002 to 2014 were identified and studied by retrospective chart review. RESULTS: Fifteen patients with median age of 68.8 yr were treated with I-125 (n = 13) or Cs-131 (n = 2) brachytherapy seeds for cases of recurrent, grade II (n = 8), or grade III (n = 7) meningioma at our institution from 2002 to 2014. These lesions originated from a variety of locations including, convexity (3), falcine (3), frontal (2), occipital (1), parietal (2), 2 sphenoid wing (2), and temporal (2), based recurrent meningiomas. Patients had a median of 2 prior open surgical interventions and received local radiation therapy with a median dose of 55 Gy prior to brachytherapy. Survival at 2.5 yr was 56% for grade II and 17% for grade III lesions. Survival was significantly associated with patient age but not tumoral pathology. Forty percent of patients required reoperations for wound complications following brachytherapy. CONCLUSION: Brachytherapy with implantation of permanent radiation seeds provides a viable alternative treatment for recurrent meningioma while carrying a significant clinical risk of wound infection and need for reoperation.

Surgical Resection and Interstitial Iodine-125 Brachytherapy for High-Grade Meningiomas: A 25-Year Series.

BACKGROUND: Atypical and malignant meningiomas can recur despite resection and radiation. OBJECTIVE: To determine outcomes of patients with recurrent atypical or malignant meningioma treated with repeat resection and permanent iodine-125 ( 125 I) brachy-therapy. METHODS: Charts of patients who underwent surgical resection and 125 I brachyther-apy implantation for atypical and malignant meningiomas between 1988 and 2013 were retrospectively reviewed. The Kaplan-Meier actuarial method was used to calculate progression-free and overall survival. The log-rank test was used to compare groups. Significance was set at P < .05. RESULTS: Forty-two patients underwent 50 resections with 125 I brachytherapy im-plantations. All patients had undergone previous resections and 85% had previously undergone radiation. Median follow-up was 7.5 years after diagnosis and 2.3 years after brachytherapy. Median time to progression after resection with 125 I brachytherapy was 20.9 months for atypical meningioma, 11.4 months for malignant meningioma, and 11.4 months for the combined groups. Median survival after re-resection and 125 I brachytherapy was 3.5 years for atypical meningioma, 2.3 years for malignant menin-gioma, and 3.3 years for all subjects. Median overall survival after diagnosis was 11.1 years for atypical meningioma, 9.1 years for malignant meningioma, and 9.4 years for all subjects. Complications occurred in 17 patients and included radiation necrosis (n = 8, 16%), wound breakdown (n = 6, 12%), hydrocephalus (n = 4, 8%), infection (n = 3, 6%), and a pseudomeningocele (n = 2, 5%). CONCLUSION: This is the largest experience with adjuvant 125 I brachytherapy for recurrent high-grade meningiomas. The outcomes support the use of adjuvant brachytherapy as an option for these aggressive tumors.

The ROAM/EORTC-1308 trial: Radiation versus Observation following surgical resection of Atypical Meningioma: study protocol for a randomised controlled trial.

BACKGROUND: Atypical meningiomas are an intermediate grade brain tumour with a recurrence rate of 39-58 %. It is not known whether early adjuvant radiotherapy reduces the risk of tumour recurrence and whether the potential side-effects are justified. An alternative management strategy is to perform active monitoring with magnetic resonance imaging (MRI) and to treat at recurrence. There are no randomised controlled trials comparing these two approaches. METHODS/DESIGN: A total of 190 patients will be recruited from neurosurgical/neuro-oncology centres across the United Kingdom, Ireland and mainland Europe. Adult patients undergoing gross total resection of intracranial atypical meningioma are eligible. Patients with multiple meningioma, optic nerve sheath meningioma, previous intracranial tumour, previous cranial radiotherapy and neurofibromatosis will be excluded. Informed consent will be obtained from patients. This is a two-stage trial (both stages will run in parallel): Stage 1 (qualitative study) is designed to maximise patient and clinician acceptability, thereby optimising recruitment and retention. Patients wishing to continue will proceed to randomisation. Stage 2 (randomisation) patients will be randomised to receive either early adjuvant radiotherapy for 6 weeks (60 Gy in 30 fractions) or active monitoring. The primary outcome measure is time to MRI evidence of tumour recurrence (progression-free survival (PFS)). Secondary outcome measures include assessing the toxicity of the radiotherapy, the quality of life, neurocognitive function, time to second line treatment, time to death (overall survival (OS)) and incremental cost per quality-adjusted life year (QALY) gained. DISCUSSION: ROAM/EORTC-1308 is the first multi-centre randomised controlled trial designed to determine whether early adjuvant radiotherapy reduces the risk of tumour recurrence following complete surgical resection of atypical meningioma. The results of this study will be used to inform current neurosurgery and neuro-oncology practice worldwide. TRIAL REGISTRATION: ISRCTN71502099 on 19 May 2014.

Hyperbaric oxygen treatment for post-radiation central nervous system injury: a retrospective case series.

Increased use of radiation therapy and increasing life spans following radiation treatment has led to an increase in the finding of post-radiation central nervous system injury in patients who have previously undergone radiation treatments. At this time, information regarding treatment for patients suffering from this serious side effect is limited and not readily available. It is imperative to examine possible treatment options, complications and success rates for these patients. This retrospective review will look at 10 patients who underwent hyperbaric oxygen therapy for post-radiation injury to the central nervous system. Review and investigation of the subjective, clinical and radiologic outcomes of these patients was conducted. It was determined that for patients with post-radiation central nervous system injury it is important to distinguish the exact diagnosis for each patient. For those patients with radiation necrosis, conclusion was made that hyperbaric oxygen (HBO2) therapy does lead to improvement in subjective, clinical and radiologic outcomes. However, the results were not consistent across all patients. For those patients with non-specific delayed radiation injury, findings showed that HBO2 does not lead to any improvement. Therefore, we conclude that for those patients who have been diagnosed with radiation necrosis of the central nervous system, we recommend HBO2 therapy as a potential treatment option for some patients.

[Management of WHO grade II and II meningiomas: retrospective study of surgical series of 36 cases at a single institution]. / Prise en charge des méningiomes OMS grade II et III : étude rétrospective monocentrique d'une série chirurgicale de 36 cas.

INTRODUCTION: Atypical and malignant meningiomas are a rare disease whose histological definition is still recent. Their management is not consensual. The aim of this study was to review the outcome, prognostic factors and the role of complementary therapies. PATIENTS AND METHODS: Between 1999 and 2007, 36 patients with atypical or malignant meningiomas were managed in our hospital. All surgical specimens were reviewed according to the 2007 WHO classification system. The sex ratio was 1.25 male, the median age was 59 years. The median follow-up was 55 months. Thirty meningiomas were atypical and six were malignant. RESULTS: Five and 10 years overall survival rate are respectively 72 and 41%, whereas 5 and 10 years progression free survival rate are 61 and 23%. We only identify female sex, age over 70 years and Karnofsky status under 70% as negative prognostic factors. CONCLUSION: Atypical and malignant meningiomas are difficult to manage and have high recurrence and poor survival rates. The prognostic of OMS II meningiomas is heterogeneous. Adjuvant radiation therapy is recommended in case of malignant menigioma or in case of atypical meningioma if incomplete surgical excision is performed.

Radiation-inducible silencing of uPA and uPAR in vitro and in vivo in meningioma.

Stereospecific radiation treatment offers a distinct opportunity for temporal and spatial regulation of gene expression at tumor sites by means of inducible promoters. To this end, a plasmid, pCArG-U2, was constructed by incorporating nine CArG elements (in tandem) of EGR1 gene upstream to uPA and uPAR siRNA oligonucleotides in a pCi-neo vector. Radiation-induced siRNA expression was detected in a meningioma cell line (IOMM-Lee). Immunoblotting and RT-PCR analyses confirmed downregulation of uPA and uPAR. A similar effect was observed in transfected cells followed by H2O2 treatment. Moreover, pre-treatment of transfected cells with N-acetyl L-cysteine blocked the silencing of uPA and uPAR, which further confirmed the oxidative damage-mediated downregulation. Cell proliferation assays and Western blot analysis for apoptotic molecules confirmed cell death in a radiation-inducible fashion. Migration and matrigel invasion assays also revealed a marked decrease in migration and invasion. Immunocytochemistry showed a marked decrease in uPA and uPAR levels in transfected and irradiated cells. H&E staining revealed a decrease in the pre-established tumor volume among the animals treated with pCArG-U2 and radiation. Immunohistochemistry of the brain sections established with intracranial tumors also revealed a marked decrease in uPA and uPAR in a radiation-inducible fashion. Taken together, our data suggest pCArG-U2 as a suitable candidate for radiation-inducible gene therapy.

Boron neutron capture therapy for recurrent malignant meningioma. Case report.

Malignant meningioma is a rare brain tumor with a high risk of recurrence. If this tumor recurs after complete resection and adjuvant radiotherapy, there is no optimal treatment to control it. The authors report the first case of recurrent malignant meningioma treated using boron neutron capture therapy (BNCT). This 25-year-old pregnant woman presented with a large frontal tumor. After her baby was born, she underwent gross-total resection of the tumor. A second resection and three Gamma Knife surgeries could not control progression of the enhancing mass; therefore, the authors applied BNCT based on their experience with it in the treatment of malignant gliomas. The minimum tumor dose and maximum brain tissue dose were estimated as 39.7 Gy-Eq and less than 9.0 Gy-Eq, respectively. Before BNCT the patient was mobile by wheelchair only, whereas 1 week after therapy she was able to walk. Twenty-two weeks later she underwent a second BNCT for tumor regrowth on the contralateral side, and the lesion was subsequently reduced. The tumor volume was markedly decreased from 65.6 cm3 at the time of the first BNCT to 31.8 cm3 at 26 weeks thereafter. The treatment of recurrent malignant meningioma is difficult and has been discouraging thus far. Data in the present case indicate that BNCT may be a promising treatment option for this challenging tumor.

Long-term tumor control and functional outcome in patients with cavernous sinus meningiomas treated by radiotherapy with or without previous surgery: is there an alternative to aggressive tumor removal?

OBJECTIVE: We report the long-term follow-up of 31 patients with cavernous sinus meningiomas who were treated either with surgery and radiotherapy (RT) or with RT alone. This retrospective review was undertaken to compare long-term efficacy and morbidity of RT with or without previous surgery versus complete, aggressive surgical removal. METHODS: Between 1980 and 1997, we performed a retrospective study of 31 patients harboring cavernous sinus meningiomas. The patient group comprised 25 women and 6 men. Patients were divided into two therapeutic categories: patients treated with surgery and RT (Group I, 17 patients) and patients treated with RT alone (Group II, 14 patients). Twenty-five patients (14 in Group I and 11 in Group II) were treated for primary tumors, and 6 patients (3 in Group I and 3 in Group II) were treated for recurrent disease. All three patients who were treated by RT alone at the time of recurrent disease had had previous surgery as initial treatment. Tumor control, treatment morbidity, and functional outcomes were evaluated for all patients. Twenty-eight patients were alive at the time of analysis, with a median follow-up period of 6.1 years. RESULTS: The progression-free survival rate was 92.8% at 10-year follow-up. Only two patients exhibited tumor progression after initial treatment. One of the patients who experienced tumor regrowth 4 years after surgery and RT benefited from additional conventional external beam radiation, and this patient exhibited no evidence of tumor progression at the last follow-up examination 6 years later. Two patients experienced cranial nerve impairment after surgery, and no patients developed late radiation toxicity. Follow-up status as measured by the Karnofsky Performance Scale deteriorated in 7% of patients and was the same or improved in 93% of patients. CONCLUSION: The results of combined surgery and RT or RT alone indicated a high rate of tumor control and a low risk of complications. Complete aggressive surgical removal of cavernous sinus meningiomas is associated with an increased incidence of morbidity and mortality and does not demonstrate a better rate of tumor control. Conventional external beam radiation seems to be an efficient and safe initial or adjuvant treatment of these lesions, and these findings should serve as a basis for evaluating new alternatives such as radiosurgery or stereotactic RT.

X-ray phototherapy for canine brain masses.

Brain masses diagnosed in 47 pet dogs as tumors by CT scans, and confirmed in 12 dogs by necropsies, were injected with iodinated contrast media and treated by a modified CT scanner, the CTRx. Twenty-six dogs that received six or more weekly treatments of about 5.6 Gy per fraction, of which about 25% was contributed by radiation from the iodine, for a median total dose of 39 Gy, had a median survival of 230 days. This compares well with the 150 days reported for 25 dogs given 46-48 Gy of cobalt-60 radiation to the whole brain, and is significantly greater than the 6 to 13 days in untreated historic controls.

Continuous low dose rate brachytherapy with high activity iodine-125 seeds in the management of meningiomas.

The purpose of this study was to evaluate if meningiomas can be effectively treated with brachytherapy using permanent implantation of high activity I-125 seeds. Thirteen patients with intracranial meningiomas were treated by means of permanent stereotactic implantation of one or more high-activity I-125 seeds. The physical characteristics of I-125 enabled us to deliver a minimum tumor dose ranging from 100 Gy to 500 Gy at a low dose rate of 5 cGy to 25 cGy per hr. Indications for this procedure included recurrence after initial surgery or as primary modality of treatment in patients who were not candidates for surgery. All 13 patients are alive at a median follow-up of 25 months. Nine of 13 patients achieved complete resolution of the tumor and in the remaining four, more than 50% reduction in tumor volume was noted at the last follow-up. No late complications were observed. We conclude from this initial data that localized high dose irradiation delivered at a low dose rate using I-125 permanent implantation is an effective, safe, and simple method in the treatment of both recurrent and primary intracranial meningiomas.

A new method for treatment of unresectable, recurrent brain tumors with single permanent high-activity 125iodine brachytherapy.

We describe a new method for treating unresectable recurrent brain tumors in previously-irradiated patients with localized high-dose intracranial brachytherapy of 10,000-30,000 rads using permanent implantation of a single high-activity 125Iodine seed. For unresectable recurrent previously-irradiated pituitary tumors, a single high-activity 125Iodine seed is permanently implanted into the center of the tumor with an interstitial needle inserted under fluoroscopic guidance via a transsphenoidal approach. For unresectable recurrent meningiomas, a single high-activity seed is permanently implanted into the tumor at craniotomy. The clinical course of five patients treated by this method is described. Excellent long-term local control was obtained in all implanted cases. There were no intraoperative, postoperative, or chronic complications.

Radiation therapy for brain tumors.

Results of radiation therapy obtained at the University of California, San Francisco over the last 25 years for various adult types of brain tumors are presented. Included are astrocytomas, ependymomas, pineal and suprasellar tumors, meningiomas, and malignant gliomas. For each tumor type considered, the disease-free survival rate appeared to be improved when subtotal resection was followed by irradiation. The lack of improvement in survival with malignant gliomas has prompted investigation into more aggressive multimodality therapies. These are discussed along with a new program using high-activity iodine 125 sources to deliver high-dose radiotherapy to malignant gliomas. It is possible that this new approach will lead to improved survival rates and be applicable to many tumors within the central nervous system.