A Royal College of Radiologists National Audit of Radiotherapy in the Treatment of Metastatic Spinal Cord Compression and Implications for the Development of Acute Oncology Services

AimsTo audit the current use of radiotherapy in UK cancer centres for the treatment of metastatic spinal cord compression against national standards that seek to optimise functional and quality of life outcomes.Materials and methodsA Royal College of Radiologists prospective national audit of patients treated with radiotherapy in UK cancer centres was carried out over a 3 month period between September and December 2008, with a repeat audit carried out in August 2012.ResultsFive hundred and ninety-six cases were received from 42 cancer centres (74%) in 2008, with data from 323 cases received from 52 (90%) centres in 2012. Ninety-three per cent (358) of patients had a diagnostic magnetic resonance imaging scan carried out within 24 h of referral for radiotherapy in 2008 compared with 205 patients (97%) in 2012. One hundred and eleven (32%) good prognosis patients were discussed with spinal surgeons; only 10 good prognosis patients were recorded as proceeding to surgery in 2008. This improved in 2012, with 94 (41% of good prognosis patients recorded as having been discussed with nine proceeding to surgery). Sixty-nine per cent of paraplegic patients in 2008 received multiple fractions of radiotherapy, which was similar to 2012 when 62% received more than a single fraction. A metastatic spinal cord compression co-ordinator was available in just over 50% of cases (164/323) and was involved in patient management in 26% of cases in 2012.ConclusionDespite level 1 evidence of the superior functional outcome and survival benefit for surgery, few good prognosis patients were recorded as having been discussed with surgeons and even fewer proceeded to surgery.     

The Potential of Targeted Radiotherapy in the Treatment of Central Nervous System Leukaemia

We describe the results of clinical studies investigating the role of monoclonal antibody (MoAb) targeted radiotherapy in the treatment of central nervous system (CNS) leukaemia. Seven children, aged 3-16 years, in second or subsequent meningeal relapse of acute lymphoblastic leukaemia (ALL), have been treated. Each patient received a single injection into the cerebrospinal fluid (CSF) of between 629 and 1,702 MBq of 131-Iodine (¹³¹I) conjugated to MoAb HD37 (CD 19, n = 2), WCMH 15.14 (CD 10, n = 4) or both antibodies (n = 1). One patient underwent a course of repeated targeted therapy following his initial treatment. Acute toxicity was manifest in five patients by a transient aseptic meningitis. Myelosuppression was observed in four children. Pharmacokinetic studies investigated whole body, blood and CSF clearance of radioisotope. Progressively more rapid systemic clearance of ¹³¹I was noted in the patient receiving repeated therapy, indicating the development of the human anti-mouse Ig (HAMA) response. Dosimetric studies revealed a radiation dose to the red bone marrow of between 0.6 and 2.2 Gy. The dose to the subarachnoid CSF was between 12.2 and 25.3 Gy, over six times higher than that to the surface tissue of the brain and spinal cord and between 40 and 140 times higher than that to the whole brain. In all but one patient, a transient complete response, in terms of disappearance of lymphoblasts from the CSF, was observed. These studies demonstrate the feasibility of targeted radiotherapy in CNS ALL. The discussion focuses on both future developments, by which the response to therapy may be improved, and the potential of this technique in becoming part of accepted therapy for meningeal leukaemia.     

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.     

Spinal Cord Gangliogliomas: A Review of 56 Patients

There have been only case reports concerning the management of intramedullary spinal cord gangliogliomas. We review our experience of 56 patients with respect to functional status, progression-free survival and long-term outcome. In this retrospective review, 56 patients, 35 males and 21 females ranging in age from 7 months to 25 years (mean, 7.0 y), underwent surgical treatment for intramedullary gangliogliomas located throughout the spinal cord. Forty-six patients had gross total resection as confirmed by postoperative imaging studies, and 10 had radical subtotal resection. Only five patients underwent postoperative irradiation or chemotherapy after surgery at our center and therefore outcome was attributed to surgery alone. There were no operative deaths, and the 5-year actuarial survival rate was 88%. The progression-free survival rate at 5 years was 67%. Neurological function in the surviving patients at recent follow-up evaluation was stable or improved in 72%. Patients have a long survival following radical surgery. These tumors have an indolent course, and radiotherapy appears to be unnecessary.     

Acute Metastatic Spinal Cord Compression: Urgent Surgery versus Radiotherapy and Treatment Result Prediction versus Actual Results

Background Context: The role of radiotherapy versus surgery in treating acute metastatic spinal cord compression (AMSCC) has changed over the years. Purpose: Our study evaluates neurological and functional outcomes following urgent surgery and radiotherapy (USFR) versus urgent radiotherapy alone in treating AMSCC. Study Design/Setting: A retrospective cohort of 54 patients with AMSCC with variable neurological deficits. Overall, 32 patients were treated with USFR, and 22 received urgent radiotherapy alone. Outcome Measures: Neurological status regarding the Asia and Frankel scores, continence and ambulation, and Kranofsky’s functional score and patient life span comprised the outcome measures. Methods: This was a retrospective EMR study. Results: USFR and radiotherapy cohorts were similar in age, gender, tumor origin, and the number of spinal metastases. The most common cause of AMSCC was carcinoma of the breast (24.1%), followed by carcinoma of the lung (16.7%) and multiple myeloma (13%). Neurological status at AMSCC presentation was similar between cohorts regarding Asia and Frankel scores, continence and ambulation, and Kranofsky’s functional score. Following USFR, 59.3% of the patients had a motor strength improvement, 31.3% regained sphincter function, and 34.4% regained ambulation, while 90% of the patients treated by radiotherapy did not show any improvement. One patient under radiotherapy lost sphincter function. The treatment received did not affect the patient’s survival. A subanalysis of patients with a short life expectancy, by Tomita and Tokuhashi scores, showed missed prediction in 29.4% of cases. Conclusion: The study supports the beneficial effect of UFSR compared to urgent radiotherapy alone in treating AMSCC in all subgroups. Early surgery improved function, motor strength, sphincter control, and ambulation without affecting life span. Prognostic scores failed to predict life span in almost one-third of the patients, requiring further investigation.     

脊髓髓内肿瘤的显微外科治疗——附53例临床分析

背景与目的：脊髓髓内肿瘤作为神经外科的一种常见疾病被广大神经外科医生所重视，其治疗效果随着显微外科技术的发展在近几年得到了较大的提高。通过总结我科近一年来收治的脊髓髓内肿瘤患者的治疗情况探讨治疗经验并评估其效果。方法：对我科2006～2007年经手术治疗的53例脊髓髓内肿瘤患者进行回顾性研究。对肿瘤病理类型、肿瘤部位、临床症状及体征、辅助检查、手术切除程度、术后疗效进行分析。结果：本组室管膜瘤49．1％，星形细胞瘤30．2％，脂肪瘤15．1％，血管母细胞瘤5．7％，本组总全切率为56．6％．次全切除率为30．2％，部分切除或活检率为13．2％，室管膜瘤全切率可达96％，无手术死亡患者。结论：通过早期诊断及早期显微手术治疗脊髓髓内肿瘤可以明显减轻患者症状，改善其生活质量，特别是对室管膜瘤及血管母细胞瘤大都可做到全切并且少有复发。     

脊髓髓内室管膜瘤的显微外科治疗——附173例临床总结

背景与目的：随着神经影像技术，显微外科技术和术中监测手段的发展，大多数脊髓髓内肿瘤的早期诊断和治疗已成为现实。本研究旨在探讨显微外科手术治疗脊髓室管膜瘤的经验。方法：回顾性研究北京天坛医院神经外科脊柱脊髓组从2000年1月至2005年4月经显微外科手术治疗的髓内室管膜瘤173例，并分析其预后影响因素。结果：肿瘤全切除163例（94．2％），近全切除8例（4．6％），大部分切除2例（1．2％），出院3-6个月门诊随访好转142例（76．3％），余随访不全。结论：积极的显微外科治疗，争取全切是髓内室管膜瘤治疗的最佳选择，术前神经功能状况、肿瘤的性质与部位、手术技巧与切除程度等都是影响预后的重要因素。     

Radiation Therapy of Metastatic Spinal Cord Compression. Multidisciplinary team diagnosis and treatment

Purpose: To evaluate the effectiveness of a multidisciplinary approach to spinal cord compression (SCC) in accordance with prospective protocol, providing a uniform approach to diagnosis, decision making concerning optimal treatment modality in any particular case of SCC, treatment performance and evaluation of treatment results. The SCC patients treated by radiation therapy are described.Materials and Methods: Patients with SCC were examined and treated by a multidisciplinary team consisting of a neurologist, radiologist, oncologist, orthopedic surgeon, and neurosurgeon. Seventy-nine patients for whom radiation was recommended received a 30Gy radiation dose to a compression-causing mass and course of high dose dexamethasone. Three fractions of 5Gy and 5 fractions 3Gy each were delivered by Co60 or 8MV photon beam in 12 days. Treatment outcome was essentially evaluated by ambulation capabilities which were considered to be the main problem of SCC. Changes in other neurologic motor, sensory and autonomic disturbances were also evaluated.Results: Seventy-two percent of the patients were already non-ambulatory at diagnosis. The first symptom was motor deficiency in only 33% of them while in all other cases it was pain. Ambulation capability was the main prognosticator of treatment outcome; 90% of patients who were ambulatory before treatment remained so while 33% of the non-ambulatory patients regained their ability to walk. The grade of motor disturbance was also an important variable: among the non-ambulatory patients, 50% of the paretic but only 14% of the plegic ones became ambulatory. Overall, 51% of the study patients were ambulatory after undergoing radiation. The ambulatory state after treatment was the main predictor for survival.Conclusion: Close cooperation of a multidisciplinary team in diagnosis and treatment according to the above protocol enabled the achievement of good results of radiation treatment in SCC. Early diagnosis and early treatment should further enhance therapeutic outcome.     

Pericarditis Associated with High-Dose Cytarabine Therapy for Acute Myeloblasts Leukemia: a Rare Complication of Therapy

Drug induced pericarditis is rare. We describe a 51 year old patient with acute myeloblasts leukemia (AML) who developed pericarditis during treatment with high dose cytarabine. The cytarabine was subsequently stopped and the patient recovered with steriod therapy. The platelet count was carefully monitored, and multiple platelet transfusions were given to prevent cardiac tamponade. Early recognition of this potentially life-threatening complication and appropriate management will usually result in the patient's recovery.     

Primary neurocytoma of the spinal cord: a case report and review of literature

Summary Most central neurocytomas (CN) and spinal neurocytomas (SN) have a bland well-differentiated histologic picture and uneventful clinical course. However, rare examples showing histologic atypia, recurrence and even CSF dissemination have been reported. Herein we report a case of recurrent spinal neurocytoma in a 24-year-old male who presented with a 2-month history of weakness and numbness of the left upper and lower limbs, and was previously operated at the same site 10 months ago. MRI revealed a contrast enhancing intramedullary mass involving C5-T1 region. Radiologic and operative impression at both surgeries was that of a glioma, possibly anaplastic. Histologic and immunohistochemical features in both resections were those of an atypical neurocytoma. The tumor showed rare mitoses, focal mild vascular proliferation in both specimens, and necrosis in the initial specimen. MIB1 labeling indices were 9 and 10%, respectively. Based on the analysis of this case and limited data from the literature, it is hypothesized that SN shows a histopathologic picture, immunoprofile and biologic behavior very similar to CN. However, the presence of histologic atypia and increased MIB1 index in SN appear to more closely correlate with tumor recurrence and a worse overall outcome, in part due to their location in the critical region of cervical spinal cord. Therefore, we hypothesize that SN with atypia requires a close clinical follow up. As in CN, radiation therapy is perhaps best reserved for atypical, progressive and recurrent SN.     

Prognostic Impact of Extramedullary Infiltration in Pediatric Low-risk Acute Myeloid Leukemia: A Retrospective Single-center Study Over 10 Years

BackgroundThe impact of extramedullary infiltration (EMI) on the clinical outcomes of pediatric patients with acute myeloid leukemia (AML) are controversial.Patients and MethodsA total of 214 pediatric patients with low-risk AML were classified as having EMI (central nervous leukemia [CNSL] and/or myeloid sarcoma [MS]) and not having EMI. Patients with isolated MS before AML diagnosis by bone marrow examination were confirmed with histopathologic examination. For patients diagnosed with AML by bone marrow examination, a thorough physical examination and radiologic imaging were used to confirm MS.ResultsMale gender, a high white blood cell count, the FAB-M5 subtype, t(8;21) and t(1;11) abnormalities, and c-KIT mutations were associated with EMI. The presence of MS was associated with a low complete remission rate (63.6% vs. 79.4%; P = .000) and poor 3-year relapse-free survival (RFS) (62.6% ± 7.5% vs. 87.0% ± 2.8%; P = .000) and 3-year overall survival (73.5% ± 7% vs. 88.8% ± 2.6%; P = .011). Multivariate analysis revealed that MS was a poor prognostic factor for RFS and overall survival. Bone infiltration was an independent risk factor for inferior RFS with MS. Patients with CNSL had a low complete remission rate (58.3% vs. 77.2%; P = .045); however, CNSL did not significantly affect the survival of low-risk patients with AML.ConclusionMS should be considered an independent risk factor to guide stratified treatment.     

Central nervous system neurocytoma and neuroblastoma in adults-report of eight cases

Summary The clinical features, pathologic findings and treatment courses of eight adults with central nervous system small-cell neuronal tumors were reviewed. Five patients had central neurocytomas, two patients central nervous system neuroblastomas, and one patient a neurocytoma-like spinal cord tumor. The neurocytomas were intraventricular, moderately cellular tumors with bland nuclei and perinuclear halos. Patients with neurocytoma were treated with surgery, radiation therapy, and/or chemotherapy, and have followed favorable clinical courses. The neuroblastomas were intraparenchymal, hypercellular tumors with necrosis and frequent mitoses. Patients with neuroblastomas were treated with surgery, radiation therapy and chemotherapy, with some clinical response, but overall poor survival. One of the two patients developed extracranial metastasis. The spinal cord tumor had histologic features of neurocytoma, and responded well to biopsy and radiation therapy. The cases are compared with the varieties of small-celled neuronal tumors described in the literature, and pathologic, histogenetic and treatment implications are discussed. This paper was presented in part at the United States and Canadian Academy of Pathology meeting, Boston, MA, March 7, 1990     

Autologous Stem Cell Transplantation in Central Nervous System Lymphoma: A Multicenter Retrospective Series and a Review of the Literature

BackgroundCentral nervous system (CNS) lymphoma is associated with poor outcomes. Autologous stem cell transplantation (ASCT) has been reported to improve outcomes when used as a consolidation strategy in primary CNS lymphoma (PCNSL) and as a salvage strategy in patients with disease relapse limited to the CNS. Herein, we describe our experience of using ASCT in PCNSL and secondary CNS lymphoma (SCNSL).Patients and MethodsWe evaluated clinical outcomes of 18 patients from 2 major academic centers with a median age of 55 (range, 46-72) years. Thirteen patients had PCNSL and 5 patients had SCNSL. Most of the cases were in the first (CR1) or second (CR2) complete remission (CR1 = 7, CR2 = 7) at the time of ASCT. Carmustine with thiotepa (n = 12, 67%) was the most commonly prescribed preparative regimen.ResultsThe median follow-up from ASCT for surviving patients was 12 (range, 0.9-115) months. The 2-year progression-free survival (PFS) and overall survival (OS) were 74% (95% confidence interval [CI], 48%-99%) and 80% (95% CI, 55%-100%), respectively. Two-year non-relapse mortality was 0%. The 2-year cumulative incidence of relapse/progression was 27% (95% CI, 10%-72%). In subgroup analysis of PCNSL patients, 2-year PFS, OS, and relapse were 71% (95% CI, 38%-100%), 71% (95% CI, 38%-100%), and 29% (95% CI, 9%-92%), respectively.ConclusionIn this retrospective study of patients with CNS lymphoma, consolidation with ASCT after high-dose methotrexate-based chemotherapy is safe and effective in reducing disease relapse.     

Reducing the Overall Treatment Time for Radiotherapy of Metastatic Spinal Cord Compression (MSCC): 3-Year Results of a Prospective Observational Multi-Center Study

BACKGROUND: This prospective multi-center study investigates a reduction of the overall treatment time for radiotherapy of MSCC, which is important for these mostly disabled patients. PATIENTS AND METHODS: Two standard fractionation schedules, 30 Gy/10 fractions/2 weeks (n = 71) and 40 Gy/20 fractions/4 weeks (n = 65) were compared for functional outcome and ambulatory status. Motor function was graded using an 8-point-scale before RT, at the end and at 6, 12 and 24 weeks after RT. A multi-variate analysis was performed for functional outcome. Included variables were the fractionation schedule and the three relevant prognostic factors. These factors are the type of primary tumor, the time of developing motor deficits before RT and the pre-treatment ambulatory status. RESULTS: The ambulatory rates were 49% in the 30 Gy group and 52% in the 40 Gy group before RT (P = 0.888), and 56% and 60% after RT (P = 0.888). Improvement of motor function occurred in 45% of the 30 Gy group and 40% of the 40 Gy group (P = 0.752). The relevant prognostic factors were comparably distributed in both groups. According to the multivariate analysis, a slower development of motor deficits (P < 0.001), a favorable histology (P = 0.040) and being ambulatory (P = 0.045) were associated with better functional outcome, whereas the fractionation schedule had no significant impact (P = 0.311). CONCLUSIONS: The data suggest both schedules to be comparably effective for functional outcome. Thus, 30 Gy/10 fractions/2 weeks should be applied instead of 40 Gy/20 fractions/4 weeks. The reduction of the overall treatment time from 4 to 2 weeks means less discomfort for the paraparetic or paraplegic patient.     

Spinal Cord Metastasis of a Non-neurofibromatosis Type-1 Malignant Peripheral Nerve Sheath Tumor: An Unusual Manifestation of a Rare Tumor

Summary Malignant peripheral nerve sheath tumors are rare spindle-cell sarcomas derived from Schwann cells or pluripotent cells of the neural crest. They arise from the spinal roots, peripheral nerves, brachial and lumbosacral plexi, cranial nerves and terminal nerve fibers within soft tissue, intestine, lung and bone. These tumors recur either locally, or metastasize distally. Most of these tumors occur in association with neurofibromatosis type 1. Spinal cord metastasis from malignant nerve sheath tumors associated with neurofibromatosis type 1 is very rare. We describe a rare case of near-total spinal cord metastasis in a patient with malignant nerve sheath tumor in the absence of neurofibromatosis, and highlight the microscopic findings and natural history of this disease process.     

Perineural Spread of Malignant Mesothelioma Resulting in an Intradural Spinal Cord Mass: Case Report

Spinal cord involvement by perineural spread of malignant mesothelioma is rare. We report a case of malignant mesothelioma that spread locally to invade the bony spine with both extradural and intradural perineural spread into the spinal canal that resulted in spinal cord compression. A 61-year-old man with a history of malignant mesothelioma presented with progressive leg weakness and right-sided arm weakness. Magnetic resonance imaging showed an enhancing lesion in the apex of the right lung with extension through the C7–T1 foramina with right hemicord enhancement. The patient underwent a C7–T1 laminectomy and right-sided C7–T1 and T1–T2 foraminotomies for neural decompression and biopsy of the lesion. Intraoperatively, tumor extended epidurally, and intradural perineural tumor spread along the C8 and T1 nerve roots into the spinal cord. Because it adhered to the spinal cord, no dissectible plane could be identified that would allow for safe total removal of the tumor. The epidural portion of the tumor, the adjacent involved bone, and the T1 nerve root were resected. Pathologic examination revealed malignant mesothelioma with bony invasion and perineural spread along the T1 nerve root. After decompression of the spinal cord, the patient had moderate improvement of his hand and leg function. Perineural spread of malignant mesothelioma resulting in spinal cord compression is an unusual clinical presentation. Intimate involvement of the spinal cord may prohibit aggressive tumor resection.     

Spinal angiolipoma: Report of three cases and review of MRI features

We report three cases of spinal angiolipoma, two intramedullary and one epidural, and review their MRI features. Diagnoses were established preoperatively in all cases. Specific MRI features including the importance of postgadolinium fat‐saturated T1‐weighted images and presence of vascular flow‐voids are discussed with histopathological correlation. A characteristic morphological appearance of intramedullary angiolipoma has been suggested.