Recurrent Intracranial Meningioma Research Articles

Advances in Boron Neutron Capture Therapy (BNCT) for Recurrent Intracranial Meningioma.

Meningiomas are the most frequently diagnosed primary intracranial tumors in adults. Surgical resection is preferred if the meningioma is accessible; for those that are not suitable for surgical resection, radiotherapy should be considered to improve local tumor control. However, recurrent meningiomas are challenging to treat, as the recurrent tumor might be located in the previously irradiated area. Boron Neutron Capture Therapy (BNCT) is a highly selective radiotherapy modality in which the cytotoxic effect focuses mainly on cells with increased uptake of boron-containing drugs. In this article, we describe four patients with recurrent meningiomas treated with BNCT in Taiwan. The mean boron-containing drug tumor-to-normal tissue uptake ratio was 4.125, and the tumor mean dose was 29.414 GyE, received via BNCT. The treatment response showed two stable diseases, one partial response, and one complete response. We also introduce and support the effectiveness and safety of BNCT as an alternative salvage treatment for recurrent meningiomas.

Recurrent Intracranial Meningioma with Pulmonary Metastases: A Case Report

We report a 40-year-old female diagnosed with histological grade III meningioma of OMS 2016 in the right side of the temporo-parietal region of skull vault. After a partial resection of the primary site, she rapidly developed unusual multiple metastasis in the pulmonary parenchyma. The patient received adjuvant radiotherapy on the residual volume with palliative decompressive intent due to the gross tumor volume. A review of the literature revealed well documented cases of benign meningiomas that metastasized in an interval of up to 10-12 years after primary tumor resection. This case illustrates that meningiomas Grade III WHO with progression disease of the primary tumor have the potential to develop hematogenous rapid metastases, emphasize the role of multimodal management and the role of genetic behavior to predict such evolution.

Re-operation for recurrent intracranial meningioma – is it worth it?

Abstract Aims Meningioma is the commonest primary brain tumour. Despite surgery, meningiomas can recur. Surgery is usually the first line treatment for recurrent meningioma. The aim was to determine the risk factors associated with clinical outcomes (performance status, morbidity, mortality, recurrence) following re-operation for recurrence of intracranial meningioma. Method Retrospective cohort study (1998-2018). Eligible patients had re-operation for local recurrence of a previously operated meningioma. Collected data included baseline clinical and imaging characteristic. Primary outcome measure was performance status after each re-operation. Secondary outcome measures were medical and surgical morbidity, recurrence-free survival (RFS) and overall survival (OS). Results Fifty-eight patients were eligible (38 female, mean age at 1st re-operation 56 years (SD=11.4)). Eleven patients (18.9%) had 2 re-operations and 3 patients (3.4%) had 3 re-operations. Median follow up was 125.5 months (IQR 73-191.5). Median time to 1st recurrence and 1st re-operation were 36.5 (IQR 24.2–79.1) and 43.8 months (IQR 22.9–102.7), respectively. Fifteen patients (25.9%) had worse performance status after 1st re-operation, compared to 6.9% (n=4) after the primary operation (Figure 1). Complication rate was 32.8% (n=19) after the primary operation compared to 46.6% (n=27) after 1st re-operation. At primary operation, there were 29 (50%) grade 1, 26 (44.8%) grade 2, and 1 (1.7%) grade 3 tumours. Median RFS after first re-operation was 68 months (95% CI 45.5-90.5) (figure 2). Median OS was 312 months (95% CI 236.9-387.1) (Figure 3). Post-operative complications were a risk factor for worsened performance status following re-operation (OR 4.91, 95% CI 1.3-18.4). Conclusion Re-operation is associated with a worse performance status and increased risk of complications. Re-operating meningiomas for radiological recurrence without symptoms increases patient morbidity. Shared-care management decision should be made with patients when considering operating for radiological recurrence only.

Extensive Pulmonary Metastases of Intracranial Anaplastic Meningioma: Case Report

Most meningiomas are benign; however anaplastic meningiomas are usually highly invasive and grow rapidly. These tumors can metastases outside the blood-brain barrier occurring to the lungs. We present an unusual case of multiple pulmonary metastases from anaplastic and recurrent intracranial meningioma in a 59-year-old male patient. Multiple pulmonary metastases from meningioma are very rare, but we should be aware of this possibility in patients with intracranial malignant meningioma especially, with potential predictive factors include anaplastic meningioma, venous sinus invasion, recurrence or previous intracranial surgery, and loss of heterozygosity.

CTNI-54. LONG-TERM USE OF EVEROLIMUS PLUS OCTREOTIDE FOR RECURRENT INTRACRANIAL OR SPINAL MENINGIOMA: A SINGLE INSTITUTION EXPERIENCE

Abstract BACKGROUND Selection of systemic therapy for recurrent meningiomas with progression after resection and/or radiation therapy represents a challenge. The combination of everolimus, an mTOR inhibitor, plus octreotide long-acting repeatable (LAR), a somatostatin agonist, suggests synergistic activity in preclinical studies. Its long-term clinical impact in recurrent meningiomas warrants further study. METHODS We reviewed the records of adult patients with recurrent intracranial or spinal meningioma (WHO grade I, II, or III), not candidates for further surgery or radiation therapy, who were treated with everolimus and octreotide, between 1/1/2015 and 06/1/2020 at MD Anderson Cancer Center. Patients received everolimus (10 mg PO daily) each 28-day cycle and octreotide 30 mg SC once monthly. Molecular features were determined by next generation sequencing (T-200–1, Oncomine). RESULTS A total of 18 patients were identified, including WHO grade I tumors (n=4), grade II (n=10), and grade III (n=4); furthermore, 8 patients harbored NF2 mutation, followed by mutations in CREBBP (n=2), NOTCH2 (n=1), MHL1 (n=1), PTEN (n=1), SETD2 (n=1), and TP53 genes (n=1). One patient had spinal meningioma. The 6- and 12-month PFS were 77.8% and 61.1%, 6- and 12-month OS were 94.4% and 83.3% respectively. Seven (38.9%) patients had tolerated treatment for more than 12 cycles, 3 (16.7%) remain on treatment for more than 24 cycles and 1 patient is still on treatment for 31 cycles. Only 1 patient required dose reduction to 7.5 mg daily due to pneumonitis, otherwise there is an acceptable toxicity profile. Four patients had resolution of trigeminal neuralgia. CONCLUSIONS In our patient population, combination treatment with everolimus and octreotide seems to have antitumor activity and proved to be safe without major side effects from long-term exposure. It also contributed to control of neuralgia. Further tissue analysis of the role of mTOR pathway and SSTR2A expression is ongoing.

Toxicity, Disease Control, and Survival Following Proton Therapy-Fractionated Re-Irradiation for Recurrent Intracranial Meningioma Not Amenable to Radiosurgery

With its finite range and sharper lateral penumbrae, proton therapy provides unique dosimetric advantages for fractionated re-irradiation of recurrent intracranial meningioma not amenable to radiosurgery due to either bulky tumor size or adjacent organs-at-risk. This analysis features the largest such clinical series to date and seeks to determine whether these dosimetric advantages translate into favorable clinical outcomes. Patients who received fractionated proton therapy re-irradiation for recurrent intracranial meningioma not amenable to radiosurgery were included. Toxicity was assessed using the NCI’s Cancer Treatment Common Terminology for Adverse Events (CTCAE) version 5.0. Local control (LC, defined as tumor control within the re-irradiated region), intracranial progression-free survival (PFS, including progression within and outside the re-irradiated region) and overall survival (OS) rates were estimated using the Kaplan-Meier method. 30 patients with follow-up ≥90 days were identified at a single institution. Median age was 65 years (range: 32 – 87). Median target volume was 61.57cc (range: 5.59 – 325.48), with 24 patients having >25cc target volume. Median follow-up for living patients was 26 months (interquartile range: 9-35 months). Prior to re-irradiation, patients received a median of 1 radiotherapy treatment (range: 1 – 5). 69% of prior treatments were radiosurgery and 31% were fractionated radiotherapy. Median time from prior radiotherapy to re-irradiation was 57 months (range: 11 – 278). Median re-irradiation dose was 54.1 CGE (range: 48.7 – 60.3). At the time of re-treatment, 16 patients had a surgically confirmed WHO grade, with 6, 9, and 1 being WHO grade III, II, and I, respectively. For the overall cohort, median PFS was 12.3 months, median OS was not reached, and one-year local control was 52.3%. For surgically confirmed WHO grade III tumors, median PFS was 11 months, median OS was 17 months, and one-year local control was 41.7%. For surgically confirmed WHO grade II tumors, median PFS was 16 months, median OS was not reached, and one-year local control was 74.1%. Acute toxicity included grade 1 fatigue, radiation dermatitis, and alopecia in 43%, 47%, and 70% of patients, respectively. Radiation-related intracranial edema occurred in 23% of patients and in every case resolved with dexamethasone. Late toxicity included 3 cases of grade 1 radiation necrosis (RN), 1 case of grade 2 RN requiring bevacizumab, and no cases of grade 3 RN. Proton therapy fractionated re-irradiation for recurrent intracranial meningioma not amenable to radiosurgery leads to favorable tumor control and survival with limited RN risk, including in high-risk tumors for which salvage therapy options remain limited.

Large volume re-irradiation for recurrent meningioma with pulsed reduced dose rate radiotherapy

Meningiomas comprise up to 30% of primary brain tumors. The majority of meningioma patients enjoy high rates of control after conventional therapies. However, patients with recurrent disease previously treated with radiotherapy have few options for salvage treatment, and systemic interventions have proven largely ineffective. The aim of this study was to determine whether pulsed reduced dose rate radiotherapy (PRDR) was well tolerated in a small cohort of patients with recurrent meningioma. We retrospectively identified eight patients with recurrent intracranial meningioma treated with PRDR from April 2013 to August of 2017 at a single institution. All patients had radiographic and/or pathologic evidence of progression prior to treatment and had previously completed conventional radiotherapy. Acute and late toxicities were graded based on CTCAE 4.0. Of eight patients, six had histologically confirmed atypical meningiomas upon recurrence. All patients were re-treated with IMRT at an apparent dose rate of 0.0667Gy/min. Median time between radiation courses was 7.7years. Median PRDR dose was 54Gy in 27 fractions to a median volume of 261.6cm3. Two patients (25%) had in field failure with a median follow up of 23.3months. PFS at 6months was 100%. All but one (87.5%) patient was still alive at last follow up. No patient experienced grade ≥ 2 acute or late toxicities. PRDR re-irradiation was well tolerated and appeared effective for a small cohort of patients with recurrent meningioma previously treated with radiotherapy. A phase II trial to assess this prospectively is in development.

Is the Simpson Grading System Applicable to Estimate the Risk of Tumor Progression After Microsurgery for Recurrent Intracranial Meningioma?

We analyzed the applicability of the Simpson grading system to estimate the risk of tumor recurrence after microsurgery for recurrent meningiomas. Correlations between the Simpson grade and the extent of resection (EOR) (gross total resection [Simpson grade I and II] vs. subtotal resection [Simpson grade ≥III]) with tumor relapse after microsurgery for meningioma recurrence were investigated compared with the findings in primary diagnosed tumors. Location-specific differences were further elucidated in subgroup analyses. A total of 829 individuals (88% in group A) with primary diagnosed meningioma and 109 patients with first postoperative recurrence (12% in group B) who underwent surgery were included. In group A, both Simpson grade (P= 0.003) and EOR (P < 0.001) correlated strongly with recurrence. In group B, Simpson grade correlated with tumor location (P= 0.030), and the risk of subtotal resection was greater in the posterior fossa (odds ratio, 5.26; P= 0.018) and skull base (odds ratio, 6.16; P= 0.002) meningiomas. Older age at tumor relapse (hazard ratio [HR], 1.05; P= 0.001), male sex (HR, 2.19; P= 0.02), and grade 2/3 histologic findings (HR, 2.18; P= 0.02). However, neither the Simpson grade nor dichotomized EOR correlated with further tumor recurrence. The frequency of postoperative complications was similar in both groups. Surgery for recurrent meningiomas is not generally associated with an increased risk of postoperative complications compared with resection of primary diagnosed tumors. However, the Simpson grade and EOR in recurrent meningiomas correlated poorly with further tumor relapse. The lower prognostic value of the tumor remnants left behind during microsurgery for recurrent meningiomas should be considered when operating on lesions that can be surgically challenging.

Evaluation of particle radiotherapy for the re-irradiation of recurrent intracranial meningioma

BackgroundWith the advance of modern irradiation techniques, the role of radiotherapy (RT) for intracranial meningioma has increased significantly throughout the past years. Despite that tumor’s generally favorable outcome with local control rates of up to 90% after ten years, progression after RT does occur. In those cases, re-irradiation is often difficult due to the limited radiation tolerance of the surrounding tissue. The aim of this analysis is to determine the value of particle therapy with its better dose conformity and higher biological efficacy for re-irradiating recurrent intracranial meningioma. It was performed within the framework of the “clinical research group heavy ion therapy” and funded by the German Research Council (DFG, KFO 214).MethodsForty-two patients treated with particle RT (protons (n = 8) or carbon ions (n = 34)) for recurrent intracranial meningioma were included in this analysis. Location of the primary lesion varied, including skull base (n = 31), convexity (n = 5) and falx (n = 6). 74% of the patients were categorized high-risk according to histology with a WHO grading of II (n = 25) or III (n = 6), in the remaining cases histology was either WHO grade I (n = 10) or unknown (n = 1). Median follow-up was 49,7 months.ResultsIn all patients, re-irradiation could be performed safely without interruptions due to side effects. No grade IV or V toxicities according to CTCAE v4.0 were observed. Particle RT offered good overall local control rates with 71% progression-free survival (PFS) after 12 months, 56,5% after 24 months and a median PFS of 34,3 months (95% CI 11,7–56,9). Histology had a significant impact on PFS yielding a median PFS of 25,7 months (95% CI 5,8–45,5) for high-risk histology (WHO grades II and III) while median PFS was not reached for low-risk tumors (WHO grade I) (p = 0,03). Median time to local progression was 15,3 months (Q1-Q3 8,08–34,6). Overall survival (OS) after re-irradiation was 89,6% after 12 months and 71,4% after 24 months with a median OS of 61,0 months (95% CI 34,2–87,7). Again, WHO grading had an effect, as median OS for low-risk patients was not reached whereas for high-risk patients it was 45,5 months (95% CI 35,6–55,3).ConclusionRe-irradiation using particle therapy is an effective method for the treatment of recurrent meningiomas. Interdisciplinary decision making is necessary to guarantee best treatment for every patient.

Recurrent intracranial meningioma with multiple pulmonary metastases – A case report

Recurrent intracranial meningioma with multiple pulmonary metastases – A case report

Application of arterial spin labeling perfusion MRI to differentiate benign from malignant intracranial meningiomas

PurposeDifferentiating WHO grade I–III of meningioma by non-invasive imaging is challenging. This study investigated the potential of MR arterial spin labeling (ASL) to establish tumor grade in meningioma patients. Material and methodsPseudo-continuous ASL with 3D background suppressed gradient and spin echo (GRASE) was acquired on 54 patients with newly diagnosed or recurrent intracranial meningioma. Perfusion patterns characterized in CBF color maps were independently evaluated by three neuroradiologists blinded to patient history, and correlated with tumor grade from histo-pathological review. ResultsThree perfusion patterns could be discerned by visual evaluation of CBF maps. Pattern 1 consisted of homogeneous hyper-perfusion of the entire tumor; pattern 2 demonstrated heterogeneous hyper-perfusion; pattern 3 showed no substantial hyper-perfusion. Evaluation of the perfusion patterns was highly concordant among the three readers (Kendall W=0.9458, P<0.0001). Pattern 1 was associated with WHO Grade I meningioma of (P<0.0001). Patterns 2 and 3 were predictive of WHO Grade II and III meningioma (P<0.0001), with an odds ratio (OR, versus pattern 1) of 49.6 (P<0.01) in a univariate analysis, and an OR of 186.4 (P<0.01) in a multivariate analysis. ConclusionQualitative evaluation of ASL CBF maps can help differentiate benign (WHO Grade I) from higher grade (WHO Grade II and III) intracranial meningiomas, potentially impacting therapeutic strategy.

Abstract 4812: A novel set of patient-derived orthotopic xenograft (PDOX) models of primary and recurrent intracranial meningioma

Abstract Background: Meningioma is the most common brain tumors in adults. Despite the overall benign nature of meningioma, cranial-base tumors are difficult to achieve complete resection while others exhibit progression and aggressive profiles characterized by high recurrence rates, pleomorphic histology, and resistance to standard treatment. The lack of clinically relevant animal models is blocking the development of novel therapies. Here, we report our establishment of orthotopic xenograft mouse models and in vitro culture systems from surgical specimens of primary and recurrent meningiomas. Material and Methods: 6 primary surgical samples (3 WHO grade I and 3 atypical), and 4 recurrent samples (1 WHO grade I, 2 atypical and 1 anaplastic meningiomas) were obtained from meningioma patients. Tumor tissues were dissociated into single cells and directly implanted into right cranial base of NOD/SCID mice (1x105 cells/mouse). Primary cultures were initiated in serum-free and traditional FBS-based media. Tumor growth was monitored by small animal MRI. Pathologic features of the PDOX models and the matched patient tumors were compared with standard H&amp;E and immunohistochemical staining. Molecular fidelity of PDOX tumor was examined through genomic analysis and comparison with the parental tumors. Results: Three of the 10 tumors were not tumorigenic, and xenograft tumor formation from 5 additional samples is pending. Growth of intracranial (cranial base) xenograft was confirmed in two samples derived from the same patient diagnosed as atypical meningioma (K029MEN) and progressed as anaplastic meningioma at recurrence (K037MEN). These patient derived orthotopic xenografts (PDOX) have since been serially subtransplanted in mouse brains for generation 2 and can be cryopreserved for long-term maintenance of tumorigenicity. The xenograft tumors replicated histopathological features (invasion, high proliferation and increased microvessel density) of their parental tumors. Genomic analysis is being performed to examine the similarities between parental tumors and the corresponding orthotopic xenograft tumors and the discrepancies between the primary and the recurrent tumor-derived models. In vitro growth of K029MEN and K037MEN as neurospheres and monolayer were maintained for 2 months and passage for 10 times. Additionally, cells from K030MEN, a WHO grade I meningioma, has been passaged as monolayer for more than 30 times. Conclusion: A novel set of meningioma PDOX models derived from matching primary and recurrent tumor was established. The xenograft tumors replicated the histopathological and key molecular features of the original patient tumors, providing a unique opportunity to understand the biology of malignant meningiomas and to conduct preclinical drug testing. Note: This abstract was not presented at the meeting. Citation Format: Huiyuan Zhang, Lin Qi, Yuchen Du, Frank K. Braun, Mari Kogiso, Sibo Zhao, Holly B. Lindsay, Sarah G. Injac, Patricia A. Baxter, Jack M. Su, Akash J. Patel, Xiao-nan Li, Baylor College of Medicine. A novel set of patient-derived orthotopic xenograft (PDOX) models of primary and recurrent intracranial meningioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4812. doi:10.1158/1538-7445.AM2017-4812

Molecular progression in unusual recurrent non-pediatric intracranial clear cell meningioma.

We report a case of a recurrent clear cell meningioma (ccm) in the frontal lobe of the brain of a 67-year-old man. The patient developed three recurrences: at 3, 10, and 12 years after his initial surgery. Histopathology observations revealed a grade 2 ccm with positivity for vimentin and epithelial membrane antigen. Expression of E-cadherin was positive only in the primary tumour and in the first available recurrence. Fluorescence in situ hybridization analyses demonstrated 1p and 14q deletions within the last recurrence. Multiplex ligation-dependent probe amplification studies revealed a heterozygous partial NF2 gene deletion, which progressed to total loss in the last recurrence. The last recurrence showed homozygous deletions in CDKN2A and CDKN2B. The RASSF1 gene was hypermethylated during tumour evolution. In this report, we show the genetic alterations of a primary ccm and its recurrences to elucidate their relationships with the changes involved in the progression of this rare neoplasm.

OS08.2 A novel set of patient-derived orthotopic xenograft (PDOX) models of primary and recurrent intracranial meningioma

OS08.2 A novel set of patient-derived orthotopic xenograft (PDOX) models of primary and recurrent intracranial meningioma

Recurrent intracranial meningioma with multiple pulmonary metastases: A case report.

Meningiomas are slow-growing tumors, which are generally considered to be benign and rarely metastasize. Although cases of extracranial metastatic meningioma have previously been reported, multiple pulmonary metastases from a benign intracranial meningioma is particularly rare. In the present report, a case of recurrent transitional meningioma with multiple lung nodules, which were demonstrated to be metastatic meningioma, is presented. A 54-year-old female patient received surgical resection of the tumor located in the left base of the middle cranial fossa in 2006. Post-surgery pathological examination indicated a transitional meningioma of World Health Organization grade I. The tumor recurred at the original site 1 year and 3 months later and was completely surgically removed once again. Radiotherapy was administered following the second surgery. Gamma Knife was used to remove the recurrent tumor 18 months following the second surgery. Simultaneously, a chest computed tomography scan revealed multiple pulmonary nodules, which were demonstrated to be metastatic meningioma following wedge resection of the superior lobe of the right lung. The clinical behavior of meningioma does not always correlate with the classification of meningioma. A higher rate of cellular proliferation is not essential for extracranial metastasis, and an individual meningioma of any type may metastasize. Comprehensive examinations should be performed for patients with a history of recurrent intracranial meningioma to detect any distant metastases as early as possible, even when the primary tumor is benign.

Late Metastasis of an Intracranial Meningioma to the Hard Palate

Meningiomas are benign neoplasms that arise from cellular elements of the meninges. Although meningiomas are usually considered as benign tumors, they have a potential to become aggressive and to metastasize to the extracranial structures. Distant metastasis most commonly occurs in lung, liver, and long bones. We present an extremely rare case of a delayed metastasis of a recurrent intracranial meningioma to the hard palate 19 years after the initial diagnosis. The patient underwent surgical excision without any complication and follow-up showed no recurrence.

Phase II study of monthly pasireotide LAR (SOM230C) for recurrent or progressive meningioma.

2040 Background: Patients with recurrent or progressive meningiomas who have exhausted surgical and radiation options have limited remaining treatment choices. Somatostatin receptors are expressed in nearly 90% of meningiomas, and somatostatin inhibits meningioma growth in vitro. The somatostatin analog octreotide had promising results in a pilot clinical study. Pasireotide LAR is a long-acting somatostatin analog that has higher binding affinity for most somatostatin receptor subtypes than octreotide. Methods: This is an open label, single arm phase II trial of monthly pasireotide LAR 60 mg intramuscularly in patients with recurrent or progressive intracranial meningioma. Treatment cycles are 28 days. Treatment continues until progressive disease or unacceptable toxicity. Restaging MRIs are performed every 3 cycles and response is assessed using Macdonald criteria. Octreotide scans are performed in all patients at baseline. Results: Twenty-six participants have been accrued, 17 (65%) of whom have atypical/malignant meningiomas, median age 56 (range 36-74), 11 men (42%), median KPS 85 (range 60-100), and 22 (85%) with previous radiation therapy. Twenty-two tumors (85%) show at least intermediate octreotide uptake. There are no radiographic responses. Of 22 evaluable patients, 16 (73%) achieved stable disease. Median PFS overall is 20 weeks (95% CI: 9-21) and PFS6 29% (benign meningiomas - median PFS 27 weeks [95% CI: 8-not yet reached], PFS6 50%; atypical/malignant meningiomas - median PFS 16 weeks [95% CI: 8-20], PFS6 20%). Toxicity has been mild except for grade 3 hyperglycemia in 5 (19%) patients, grade 4 hyperglycemia in 1 (4%) patient, and grade 3 lipase in 2 (8%) patients. Conclusions: Pasireotide LAR is a well-tolerated somatostatin analog that is under investigation for heavily pre-treated, recurrent meningiomas. Updated results will be presented at the meeting.

Metastatic Meningioma to the Lungs

Meningioma with extracranial metastases is a rare occurrence. However, the lungs are the most common site of extracranial metastases. We describe a case of a patient with recurrent intracranial meningioma and intrapulmonary metastases.

Resection of multiple pulmonary metastases from a recurrent intracranial meningioma

Surgical resection of multiple pulmonary metastases from a recurrent intracranial meningioma in a 53-year-old woman is presented. The primary tumor was diagnosed in 1984 and partially excised in early 1985. The tumor recurred and was re-excised in 1989 and 1992. A fourth intracranial recurrence was noted in 1993, accompanied by multiple bilateral pulmonary metastases. The metastases were excised using staged thoracotomies in July and September 1994. The patient is surviving with cranial tumor residual.