Stereotactic Radiosurgery for Cranial and Spinal Hemangioblastomas: A Single-Institution Retrospective Series.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) has been an attractive treatment modality for both cranial and spinal hemangioblastomas, especially for multiple lesions commonly associated with von Hippel-Lindau (VHL) disease. This study aims to provide the largest long-term analysis of treatment efficacy and adverse effects of SRS for cranial and spinal hemangioblastomas at a single institution. METHODS: We evaluated the clinical and radiological outcomes of patients with hemangioblastomas treated with CyberKnife SRS at our institute from 1998 to 2022. The follow-up data were available for 135 hemangioblastomas in 35 patients. Twenty-eight patients had 123 hemangioblastomas associated with VHL, and 7 had 12 sporadic hemangioblastomas. The median age was 36 years, and the median tumor volume accounted for 0.4 cc. The SRS was administered with the median single-fraction equivalent dose of 18 Gy to the 77% median isodose line. RESULTS: At a median follow-up of 57 months (range: 3-260), only 20 (16.2%) of the VHL-associated and 1 (8.3%) sporadic hemangioblastomas progressed. The 5-year local tumor control rate was 91.3% for all hemangioblastomas, 91.7% among the sporadic lesions, and 92.9% in patients with VHL. SRS improved tumor-associated symptoms of 98 (74.8%) of 131 symptomatic hemangioblastomas, including headache, neck pain, dizziness, visual disturbances, dysesthesia, ataxia, motor impairment, seizures, and dysphagia. Two patients developed radiation necrosis (5.7%), and 1 of them required surgical resection. CONCLUSION: SRS is a safe and effective treatment option for patients with hemangioblastomas in critical locations, such as the brainstem, cervicomedullary junction, and spinal cord, and in patients with multiple hemangioblastomas associated with VHL disease.

[Case of Long-Term Response to Radiotherapy for Intramedullary Spinal Cord Metastasis from Ovarian Cancer after Surgery].

Intramedullary spinal cord metastasis(ISCM)often causes spinal cord neuropathy and should be treated as an oncologic emergency. However, it recurs in most cases after treatment, ISCM is a disease with a very unfavorable prognosis. Herein, we report a successfully treated case of ISCM with emergent and high-dose radiotherapy. A 53-year-old woman had difficulty walking without assistance 2 years after surgery for ovarian cancer. She received emergent radiotherapy at a total dose of 50 Gy in 25 fractions. Her neurological symptoms dramatically improved over 3 weeks after radiotherapy. ISCM has been controlled using the imaging tests at 5 years after radiotherapy. We believe that both emergent and high-dose radiotherapy were effective for ISCM.

Multi-institutional Characterization of Outcomes for Pediatric and Young Adult Patients With High-Risk Myxopapillary Ependymoma After Radiation Therapy.

PURPOSE: Myxopapillary ependymoma (MPE) is a rare, typically slow-growing subtype of spinal ependymomas. There are no standard guidelines for radiotherapy and long-term outcomes after radiation, particularly patterns of relapse, for pediatric and young adult (YA) patients with MPE remain under-characterized. METHODS AND MATERIALS: This is an Institutional Review Board-approved multi-institutional retrospective cohort study of 60 pediatric and YA patients diagnosed with MPE and received radiotherapy between 2000-2020. Clinical and treatment characteristics, and long-term outcomes were recorded. Site(s) of progression was compared to radiation fields. Survival outcomes were analyzed using Kaplan-Meier method. Cumulative incidence of local in-field progression (CILP) after initial radiotherapy was analyzed using Gray's method with out-of-field-only progression as a competing risk. Univariate analyses were performed using Cox proportional hazard's model. RESULTS: The median age at radiation was 14.8 years (range: 7.1-26.5). At time of radiotherapy, 45 (75.0%) and 35 (58.3%) patients had gross residual and multifocal disease, respectively. Forty-eight (80.0%), seven (11.7%) and five (8.3%) patients received involved field radiotherapy, craniospinal irradiation, and whole spine radiation, respectively. Median follow-up from end of radiotherapy was 6.2 years (range: 0.6-21.0). Five-year overall survival, progression-free survival, and CILP were 100%, 60.8% and 4.1%, respectively. Both local recurrences were at sites of gross residual disease. Of the eighteen out-of-field first recurrences after radiotherapy, all were superior to the initial treatment field and nine had intracranial relapse. On univariate analyses, distant-only recurrence before radiation (HR: 4.00, 95% CI: 1.54-10.43, p = 0.005) was significantly associated with shorter time to progression. CONCLUSIONS: While the risk of recurrence within the radiation field is low, pediatric and YA patients with high-risk MPE remain at risk for recurrences in the spine above the radiation field and intracranially after radiotherapy. Future prospective studies are needed to investigate the appropriate radiation field and dose based on the extent of metastases.

Efficacy and toxicity of primary re-irradiation for malignant spinal cord compression based on radiobiological modelling: a phase II clinical trial.

BACKGROUND: The efficacy and safety of primary re-irradiation for MSCC are not known. Our aim was to establish the efficacy and safety of biologically effective dose-based re-irradiation. METHODS: Patients presenting with MSCC at a previously irradiated spine segment, and not proceeding with surgical decompression, were eligible. A 3 Gray per fraction experimental schedule (minimum 18 Gy/6 fractions, maximum 30 Gy/10 fractions) was used, delivering a maximum cumulative spinal dose of 100 Gy2 if the interval since the last radiotherapy was within 6 months, or 130 Gy2 if longer. The primary outcome was a change in mobility from week 1 to week 5 post-treatment, as assessed by the Tomita score. The RTOG SOMA score was used to screen for spinal toxicity, and an MRI performed to assess for radiation-induced myelopathy (RIM). RESULTS: Twenty-two patients were enroled, of whom eleven were evaluable for the primary outcome. Nine of eleven (81.8%) had stable or improved Tomita scores at 5 weeks. One of eight (12.5%) evaluable for late toxicity developed RIM. CONCLUSIONS: Re-irradiation is an efficacious treatment for MSCC. There is a risk of RIM with a cumulative dose of 120 Gy2. CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland (ICORG 07-11); NCT00974168.

Cervical Spinal Ependymoma With Hemorrhage in a Renal Transplant Patient.

Ependymomas are the most common intramedullary spinal tumors in adults and constitute around 20% of all spinal tumors in adults. There are 3 subgroups of ependymomas according to World Health Organization classification: subependymoma or myxopapillary (grade 1), ependymoma (grade 2), and anaplastic (grade 3). Therapy for patients is aimed at safe and total surgical removal and, in selected cases, postoperative radiotherapy. Bleeding from a spinal ependymoma, with subsequent urgent surgery, is extremely rare. Here, we present a case of a renal transplant patient who had a cervical ependymoma. Although a considerable volume of peritumoral blood was observed during surgery, the patient had no neurologic deficits and no signs of deterioration.

Bicentric Treatment Outcomes After Proton Therapy for Nonmyxopapillary High-Grade Spinal Cord Ependymoma in Children.

PURPOSE: Few studies report outcomes in children treated with radiation for nonmyxopapillary ependymoma of the spinal cord, and little evidence exists to inform decisions regarding target volume and prescription dose. Moreover, virtually no mature outcome data exist on proton therapy for this tumor. We describe our combined institutional experience treating pediatric classical/anaplastic ependymoma of the spinal cord with proton therapy. METHODS AND MATERIALS: Between 2008 and 2019, 14 pediatric patients with nonmetastatic nonmyxopapillary grade II (n = 6) and grade III (n = 8) spinal ependymoma received proton therapy. The median age at radiation was 14 years (range, 1.5-18 years). Five tumors arose within the cervical cord, 3 within the thoracic cord, and 6 within the lumbosacral cord. Before radiation therapy, 3 patients underwent subtotal resection, and 11 underwent gross-total or near total resection. Two patients received chemotherapy. For radiation, the clinical target volume received 50.4 Gy (n = 8), 52.2 (n = 1), or 54 Gy (n = 5), with the latter receiving a boost to the gross tumor volume after the initial 50.4 Gy, modified to respect spinal cord tolerance. RESULTS: With a median follow-up of 6.3 years (range, 1.5-14.8 years), no tumors progressed. Although most patients experienced neurologic sequela after surgery, only 1 developed additional neurologic deficits after radiation: An 18-year-old male who received 54 Gy after gross total resection of a lumbosacral tumor developed grade 2 erectile dysfunction. There were 2 cases of musculoskeletal toxicity attributable to surgery and radiation. At analysis, no patient had developed cardiac, pulmonary, or other visceral organ complications or a second malignancy. CONCLUSION: Radiation to a total dose of 50 to 54 Gy can be safely delivered and plays a beneficial role in the multidisciplinary management of children with nonmyxopapillary spinal cord ependymoma. Proton therapy may reduce late radiation effects and is not associated with unexpected spinal cord toxicity.

Stereotactic body radiotherapy for intramedullary metastases: a retrospective series at the Oscar Lambret center and a systematic review.

BACKGROUND: Intramedullary metastasis (IMM) is a rare disease with poor prognosis. The incidence of IMMs has increased, which has been linked to improved systemic treatment in many cancers. Surgery and/or radiotherapy are the most commonly used treatments; only small-sample retrospective studies and case reports on stereotactic body radiotherapy (SBRT) have reported acceptable results in terms of local control and clinical improvement, with no reported toxicity. Thus, we performed this monocentric retrospective study on five cases treated with SBRT for IMMs, which we supplemented with a systematic review of the literature. METHODS: We included all patients treated for IMM with SBRT. The target tumor volume, progression-free survival, prescription patterns in SBRT, survival without neurological deficit, neurological functional improvement after treatment, and overall survival were determined. RESULTS: Five patients treated with a median dose of 30 Gy in a median number of fractions of 5 (prescribed at a median isodose of 86%) included. The median follow-up duration was 23 months. Two patients showed clinical improvement. Three patients remained stable. Radiologically, 25% of patients had complete response and 50% had stable disease. No significant treatment-related toxicity was observed. CONCLUSION: SBRT appears to be a safe, effective, and rapid treatment option for palliative patients.

[A Case of Emergency Radiotherapy for Intramedullary Spinal Cord Metastasis from Breast Cancer].

Intramedullary spinal cord metastasis(ISCM)is rare. However, with advances in diagnostic imaging, the incidence of ISCM is increasing. We herein present a case of breast cancer metastasis in the lower thoracic spinal intramedullary area in a patient who was then successfully treated with emergency radiotherapy. A 56‒year‒old woman with breast cancer was admitted to our hospital due to rapidly progressing weakness in both legs and bladder and rectal disturbance. Spinal MRI revealed a gadolinium‒enhancing intramedullary lesion. The patient was treated with emergency radiotherapy and oral steroids. Although the prognosis of ISCM is extremely poor, emergency radiotherapy could be an effective treatment for ISCM to improve the patient's quality of life(QOL).

Lumbar Laminoplasty for Resection of Myxopapillary Ependymoma of the Conus Medullaris: 2-Dimensional Operative Video.

Myxopapillary ependymomas are slow-growing tumors that are located almost exclusively in the region of the conus medullaris, cauda equina, and filum terminale of the spinal cord. Surgical intervention achieving a gross total resection is the main treatment modality. If, however, a gross total resection cannot be achieved, surgery is augmented with radiation therapy. In this video, we present the case of a 27-yr-old male with persistent back pain and radiculopathy who was found to have a myxopapillary ependymoma that was adherent to the conus. Preoperative imaging demonstrated that the tumor was displacing the conus and nerve roots ventrally. A laminoplasty at L1-L2 was performed with near-total resection because of the intimate involvement of neural tissue. The key features of the video include performing laminoplasty and rationale, and performing maximum safe tumor resection with a combination of bipolar cautery, suction, and ultrasonic aspiration augmented with frequent stimulation, gel foam pledgets intradurally, and achieving a watertight closure of the dura and fascia. The patient tolerated the surgery well without any complications. Given his gross residual disease along the conus and young age, he was at a high risk for continued tumor growth without adjuvant therapy, with a recurrence rate of roughly 33% to 45% in patients who underwent subtotal resection. With the addition of adjuvant radiation therapy, the recurrence rate is 20% to 29%.1,2 He was discharged to home with a plan for conventional fractionated external beam radiation. At the most recent follow-up, he reported decreased back pain and radiculopathy. Appropriate patient consent was obtained.

Intensity-modulated radiation therapy administered to a previously irradiated spine is effective and well-tolerated

Purpose This study sought to discern the clinical outcomes of intensity-modulated radiation therapy (IMRT) administered to the spine in patients who had undergone previous radiotherapy. Methods A total of 81 sites of 74 patients who underwent previous radiotherapy administered to the spine or peri-spine and subsequently received IMRT for the spine were analyzed in this study. The prescribed dose of 80 Gy in a biologically effective dose (BED) of α/β = 10 (BED10) was set as the planning target volume. The constraint for the spinal cord and cauda equine was D0.1 cc ≤ 100 Gy and ≤ 150 Gy of BED for re-irradiation alone and the total irradiation dose, respectively. Results The median follow-up period was 10.1 (0.9–92.1) months after re-irradiation, while the median interval from the last day of the previous radiotherapy to the time of re-irradiation was 15.6 (0.4–210.1) months. Separately, the median prescript dose of re-irradiation was 78.0 (28.0–104.9) of BED10. The median survival time in this study was 13.9 months, with 1-, 3-, and 5-year overall survival rates of 53.7%, 29.3%, and 26.6%, respectively. The 1-, 3-, and 5-year local control rates were 90.8%, 84.0%, and 84.0%, respectively. Neurotoxicity was observed in two of 72 treatments (2.8%) assessed after re-irradiation. Conclusion Re-irradiation for the spine using IMRT seems well-tolerated. Definitive re-irradiation can be a feasible treatment option in patients with the potential for a good prognosis (AU)

Grade III intradural extramedullary anaplastic ependymoma managed with near-complete resection and adjuvant radiotherapy: a case report.

INTRODUCTION: Of the 23 cases of spinal intradural-extramedullary ependymomas which have been reported to date, 11 were diagnosed as anaplastic. Here we present a very rare case of a thoracic intradural-extramedullary (not intramedullary) anaplastic ependymoma in an adult along with a literature review. CASE PRESENTATION: A 29-year-old man presented with rapidly progressive gait disturbance, a sensory-deficit below the trunk and urination disorders that had begun a few months earlier. Magnetic resonance imaging of his thoracic spine revealed a dorsal-located intradural-extramedullary tumor at T4-5. The rapid deterioration of his symptoms within several months led him to refer to our department for surgery. Within one month the size of tumor increased to involve the T4-6 level, consequently worsening his gait disturbance. He underwent surgery and tumor mass was resected. However, there was leptomeningeal dissemination of the tumor cells on the surface of cord. A near-total resection was therefore achieved. Histopathology revealed the resected specimen had immunoreactivity for EMA/Vimentin/CD56/CD99/S-100/GFAP, with a Ki-67 index of ~35%. These factors led to the diagnosis of anaplastic ependymoma. Seven weeks postoperatively he received adjuvant radiotherapy to the whole brain and the whole spinal cord. He recovered as an independent ambulator without recurrence 1 year postoperatively. DISCUSSION: Because of their rarity, there are no clear treatment or adjuvant therapy guidelines for spinal anaplastic ependymoma. Adjuvant radiotherapy to the whole brain and spinal cord was necessarily indicated after near-total resection. Although the patient's condition has not recurred 1 year after surgery, careful and serial follow-up is necessary for this individual.

Outcomes following limited-volume proton therapy for multifocal spinal myxopapillary ependymoma.

PURPOSE: Spinal myxopapillary ependymoma (MPE) often presents with a multifocal distribution, complicating attempts at resection. There remains no standard approach to irradiating these patients. We report disease control and toxicity in pediatric patients with multifocal spinal MPE treated with limited-volume proton therapy. MATERIALS/METHODS: Twelve patients (≤21 years old) with multifocal spinal MPE were treated between 2009 and 2018 with limited-volume brain-sparing proton therapy. Median age was 13.5 years (range, 7-21). Radiotherapy was given as adjuvant therapy after primary surgery in five patients (42%) and for recurrence in seven (58%). No patient received prior radiation. Eleven patients (92%) had evidence of gross disease at radiotherapy. Eleven patients received 54 GyRBE; one received 50.4 GyRBE. Treatment toxicity was graded per the CTCAEv4.0. We estimated disease control and survival using the Kaplan-Meier product-limit method. RESULTS: The median follow-up was 3.6 years (range, 1.8-10.6). The five-year actuarial rates of local control, progression-free survival, and overall survival were 100%, 92%, and 100%, respectively. One patient experienced an out-of-field recurrence in the spine superior to the irradiated region. No patients developed in-field recurrences. Following surgery and irradiation, one patient developed grade three spinal kyphosis and one patient developed grade 2 unilateral L5 neuropathy. CONCLUSION: 54 GyRBE to a limited volume appears effective for disseminated spinal MPE in both the primary and salvage settings, sparing children the toxicity of full craniospinal irradiation. Compared with historical reports, this approach using proton therapy improves the therapeutic ratio, resulting in minimal side effects and high rates of disease control.

Surgical and Radiotherapeutic Management of Malignant Extradural Spinal Cord Compression.

Malignant spinal cord compression is one of the most dreaded complications of advanced malignancy, with patients presenting with progressive paralysis, paresthesia and/or autonomic dysfunction. The choice of management should be guided by the expected prognosis and outcome, not just from a neurological function point-of-view but also from the metastatic cancer itself. The main indications for surgery are: impending cord compression, spinal instability from tumour progression, bony retropulsion, for tissue diagnosis and for pain resistant to conventional therapies. Here, surgical principles, traditional and novel techniques and complications will be reviewed. For radiotherapy, multiple randomised studies have shown that for most patients a single fraction of external radiation has the same functional outcomes compared with multi-fractionation protocols. The experience of a specialised centralised interdisciplinary team will also be discussed.

Intramedullary spinal nephroblastoma in a mixed breed dog.

A 1-year-old male mixed breed dog presented for the evaluation of progressive hindlimb paresis. Neurological examination indicated a spinal cord lesion between the 3rd thoracic and 3rd lumbar vertebrae. Magnetic resonance imaging (MRI) revealed an intramedullary spinal cord lesion located at the level of the 1st and 2nd lumbar vertebrae. Following cytoreductive surgery of the mass, palliative radiation therapy was administered. A diagnosis of nephroblastoma was made based on histological examination. After radiation therapy, the disappearance of the spinal lesion was confirmed by MRI. The dog was improved from gait abnormality and alive at 16 months postoperatively, with slight signs of neurological dysfunction.

Stereotactic Radiosurgery for Benign Spinal Tumors.

Benign spinal tumors are rare clinical conditions, including meningiomas, schwannomas, and neurofibromas. Although these tumors are usually treated with open surgical resection, spinal stereotactic radiosurgery may be a safe and effective alternative to surgery in selected patients.

Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression.

BACKGROUND: The optimal EBRT schedule for MSCC is undetermined. Our aim was to determine whether a single fraction (SF) was non-inferior to five daily fractions (5Fx), for functional motor outcome. METHODS: Patients not proceeding with surgical decompression in this multicentre non-inferiority, Phase 3 trial were randomised to 10 Gy/SF or 20 Gy/5Fx. A change in mobility from baseline to 5 weeks for each patient, was evaluated by a Modified Tomita score: 1 = 'Walk unaided', 2 = 'With walking aid' and 3 = 'Bed-bound'. The margin used to establish non-inferiority was a detrimental change of -0.4 in the mean difference between arms. RESULTS: One-hundred and twelve eligible patients were enrolled. Seventy-three patients aged 30-87 were evaluated for the primary analysis. The 95% CI for the difference in the mean change in mobility scores between arms was -0.12 to 0.6. Since -0.4 is not included in the interval, there is evidence that 10 Gy/SF is non-inferior to 20 Gy/5Fx. One grade 3 AE was reported in the 5Fx arm. Twelve (26%) patients in the 5Fx arm had a Grade 2-3 AE compared with six (11%) patients in the SF arm (p = 0.093). CONCLUSION: For mobility preservation, one 10-Gy fraction is non-inferior to 20 Gy in five fractions, in patients with MSCC not proceeding with surgical decompression. CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland ICORG 05-03; NCT00968643; EU-20952.

National trends in management of adult myxopapillary ependymomas.

Myxopapillary ependymomas (MPE) are WHO Grade I ependymomas that annually occur in 0.05-0.08 per 100,000 people. Surgical resection is the recommended first line therapy. Due to the rarity of the disease, there is a relatively poor understanding of the use of radiotherapy (RT) in managing this disease. The National Cancer Database (NCDB) was analyzed for patterns of care foradult MPE diagnosed between 2002 and 2016. Of 753 qualifying cases, the majority of patients underwent resection (n = 617, 81.9%). A relatively small portion received RT (n = 103, 13.3%) with most receiving RT post-operatively (n = 98, 95.1%). The likelihood of patients to undergo resection and RT was associated with patient age at diagnosis (p = 0.002), tumor size (p < 0.001), and race (p = 0.017). Chemotherapy was not widely utilized (0.27% of patients). One limitation of our analysis is that there was no data on progression free survival (PFS), an important outcome given the high survival rate in this disease. Surgery remains the primary means to manage adult MPE. For spinal MPE, it is understood that gross total resection (GTR) should be attempted whenever possible as GTR has been associated with improved PFS in several studies. The impact of RT on overall survival (OS) is indeterminate given the 1.6% death rate in the cohort. Analyses of the impact of RT on PFS in a larger database would be beneficial for determining an algorithm for post-operative and definitive RT in this disease entity.

Clinical characteristics and surgical outcomes of spinal myxopapillary ependymomas.

Spinal myxopapillary ependymoma (SME) is a rare pathological variant of ependymoma, which most commonly occurs in the cauda equina and filum terminale of the spinal cord. Although SME is considered as a benign entity, histologically corresponding to WHO grade I, local recurrence and metastasis have been reported in many cases. The purpose of this large-scale, single-center study was to investigate the clinical characteristics and surgical outcomes of SME. A total of 34 consecutive patients diagnosed with SME were enrolled in this retrospective study. All patients underwent magnetic resonance imaging (MRI) and were treated with surgical resection. Individual clinical data were collected, and surgical outcomes were evaluated during the follow-up period. There were 21 males and 13 females, with an average age of 29.97 years. Clinical symptoms included back pain (82.4%), weakness (44.1%) and numbness (20.6%) in extremities, and sphincter dysfunction (26.5%). The tumor locations included lumbar segments (52.9%), thoracolumbar segments (23.5%), lumbosacral segments (17.6%), and thoraco-lumbo-sacral segments (5.9%). On MRI, all SMEs appeared hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging, with remarkable enhancement. Gross total resection was achieved in 18 patients, and subtotal resection (STR) was achieved in 16 patients. After an average follow-up period of 41.5 months, recurrence was noted in 5 patients (5 of 16) who underwent STR. SMEs have some characteristic features on MRI which can facilitate the preoperative diagnosis. Complete surgical resection is the best treatment of choice with a favorable outcome. In cases of incomplete resection, postoperative radiotherapy may be an effective alternative.