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Year : 2015  |  Volume : 52  |  Issue : 4  |  Page : 590--597

Role of adjuvant radiation in the management of central neurocytoma: Experience from a tertiary cancer care center of India

S Mallick1, S Roy1, S Das1, NP Joshi2, V Roshan1, AK Gandhi1, M Jana3, PK Julka1, GK Rath1,  
1 Department of Radiation Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
2 Department of Radiation Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences; Department of Radiation Oncology, Max Super-Speciality Hospital, Saket, New Delhi, India
3 Department of Radiology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
S Roy
Department of Radiation Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi


BACKGROUND AND OBJECTIVE: Neurocytoma (NC) is a rare benign neuronal tumor. A complete excision remains curative for most of these tumors, but atypical histology and extra-ventricular location often necessitates adjuvant therapy. We intended to explore the clinico-pathological features and treatment outcome in patients of NC in our institute. MATERIALS AND METHODS: Medical records were reviewed and data collected on NC over a 6-year period (2006-2012) from the departmental archives. Disease free survival (DFS) was analyzed by Kaplan-Meier method. RESULTS: A total of 18 patients met the study criteria. Fourteen patients had intra-ventricular neurocytoma (IVNC), right lateral ventricle being the most common site of origin. Gross total resection and near total resection were achieved in eight cases each whereas tumor decompression and biopsy could be done in two cases. On post-operative histopathological examination, eight patients were found to have atypical NC while 10 patients had typical NC. All patients underwent adjuvant radiation. The median dose of post-operative radiation was 56 Gy. All patients were alive at their final follow-up. One patient had both clinical and radiological evidence of local relapse. In the evaluable patients (n = 18), after a median follow-up of 35 months the DFS rate at 2 years and 3 years are 100% and 83% respectively. CONCLUSION: Use of adjuvant radiation to a total dose of 56 Gy enhances the local control and achieves superior survival in patients of NC. Use of 3D conformal planning techniques may help us to achieve better therapeutic ratio in patients with NC.

How to cite this article:
Mallick S, Roy S, Das S, Joshi N P, Roshan V, Gandhi A K, Jana M, Julka P K, Rath G K. Role of adjuvant radiation in the management of central neurocytoma: Experience from a tertiary cancer care center of India.Indian J Cancer 2015;52:590-597

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Mallick S, Roy S, Das S, Joshi N P, Roshan V, Gandhi A K, Jana M, Julka P K, Rath G K. Role of adjuvant radiation in the management of central neurocytoma: Experience from a tertiary cancer care center of India. Indian J Cancer [serial online] 2015 [cited 2020 Feb 21 ];52:590-597
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Neurocytoma (NC) is a rare benign neuronal tumor. It is more common in young adults. It arises from the neuronal cells of the septum pellucidum and the subependymal cells of the lateral ventricles.[1] Less than 500 cases have been reported since 1982, when this entity was established.[2] Neurocytomas can be divided in two major groups, typical (well-differentiated) neurocytomas and atypical neurocytomas. Atypical lesions are characterized by a MIB-1 (Antibody used for determining Ki-67 proliferative index) labeling index >3% and atypical histologic features such as necrosis, increased mitotic activity and vascular proliferation.[3] A complete excision remains curative for most of these tumors, but atypical histology and extra-ventricular location often necessitates adjuvant therapy. Adjuvant radiotherapy (RT) is found to be associated with a better local control and survival. The aim of this study was to evaluate retrospectively the clinico-pathological features and treatment outcome in patients of neurocytoma attending the institute rotary cancer hospital in our institute from 2006 to 2012.

 Materials and Methods


Medical records were reviewed and data collected on all neurocytoma patients over a 6 year period (2006-2012) from the departmental archives. Ethical clearance was obtained from the institutional review board. Details regarding demographic data, clinical, radiological and pathological data, treatment details, response to treatment and survival were evaluated. Complete response (CR), partial response (PR), stable disease and progressive disease were defined as per the Response Evaluation Criteria in Solid Tumors.

Pre-treatment evaluation

Patients referred for adjuvant treatment were evaluated thoroughly. The imaging, surgical details and histopathology were reviewed for the study. The common indications for delivering adjuvant radiation in these patients were recurrent tumor, atypical histology and residual disease as evident in immediate post-operative imaging. In our institute, 18 patients were found to have received adjuvant radiation therapy over this period. A total of 20 patients were found to have one or more indications for delivering adjuvant radiation over this period, but 2 patients defaulted.

Extent of surgery

Extent of resection was defined as gross-total resection ([GTR], no residual enhancement), near-total resection ([NTR], thin rim of enhancement in resection cavity only) or sub-total resection ([STR], residual nodular enhancement) based on immediate post-operative magnetic resonance imaging (MRI) findings.

RT planning

The RT planning required a customized thermoplastic immobilization device in all cases with the patient positioned supine with hands by side. With the passage of time, conventional two-dimensional planning had gradually evolved into conformal 3D planning. For three dimensional planning contrast enhanced computed tomography (CECT) simulation with was done for patients using Philips large bore CT scanner with 3 mm slice thickness. The planning was done using Eclipse™ treatment planning system (TPS) version 6.5 or Pinnacle™ TPS version 8.0 for three dimensional conformal radiation delivery techniques (3D-CRT) and Brain lab I-planning system for stereotactic radiotherapy (SRT). The gross tumor volume (GTV) was defined as the residual tumor evident on the planning CT scan. No CTV was delineated for typical neurocytoma and a 5 mm uniform expansion was given around the GTV to form the planning target volume (PTV). For atypical neurocytoma (NC), the entire post-operative bed was delineated to form the clinical target volume (CTV). The CTV volume was restricted with respect to the natural barrier such as bone. A five mm uniform expansion was given around CTV to define the PTV. The dose delivered varied from 50 Gray (Gy) to 60 Gy. Two Gray was delivered in each fraction of radiation. During the RT planning of intracranial tumors highest priority was given to achieve a conformal dose distribution covering the PTV followed by maximal sparing of the optic structures. We evaluated the patients once every week while on RT, for assessment of any radiation induced morbidity and proper management was done to prevent unplanned interruption in radiation therapy. Homogeneity index (HI) was defined as the ratio of the dose received by 5% of volume of PTV and that received by 95% volume of PTV. Conformity index (CI) was defined as the ratio of the volume of PTV getting the prescribed dose and volume of the body receiving the prescribed dose.

Follow-up policy

After completion of treatment the patients were first reviewed after 4 weeks with repeat imaging, preferably contrast enhanced magnetic resonance imaging (CEMRI) or at least a CECT of head. Then the patients were reviewed once every 3 months in the 1st year after completion of therapy, once every 6 months from 2nd year to 5th year and after that they were followed-up once in a year. Imaging studies were repeated at 6 months interval.

Statistical method

Event free survival (EFS) was calculated from the date of diagnosis to the date of any event such as death, progression or recurrence. EFS was analyzed by Kaplan-Meier method. SPSS statistical software version 18 (manufacturer: IBM corporation USA) was used for the analysis.


Patient demographics

A total of 18 patients met the study criterion. The male:female ratio was 1.25:1. The median age at presentation was 23 years (range: 8-36 years) [Table 1]. The median Karnofsky's Performance Status score at presentation was 80. Headache was the most frequent presentation (n = 13) and it correlated with the ventricular obstruction. Vomiting, hemiparesis and visual complaints were found in 6, 4 and 6 patients respectively [Figure 1]. Only 2 patients presented with generalized tonic-clonic seizure. One patient had a complaint of paraparesis, sensory loss and numbness below the level of the umbilicus. The median duration of symptoms was 6 months (range: 1-48 months).{Table 1}{Figure 1}


A total of 15 patients were having a pre-operative CEMRI of brain while 3 patients had CECT of brain. In this cohort, 14 patients were found to be IVNC and the rest were extra-ventricular neurocytoma (EVNC) (n = 4). Right lateral ventricle (n = 9) was the most common site of epicenter followed by 3rd ventricle (n = 4) for IVNC. EVNC were found to arise from the frontal lobe, perimesencephlic area and thalamus. One patient had an intramedullary spinal neurocytoma (involving D8-L1). The difference between IVNC and EVNC in our study cohort has been shown in [Table 4]. The tumors were iso-intense to hyper-intense in T1 and hyperintense T2 weighted MRI images [Figure 2]. After intravenous Gadolinium administration, the tumors showed heterogeneous enhancement. A solid cystic variegated mass was the most common appearance in MRI (n = 4). Only two cases revealed evidence of calcification in MRI. An enhancing mass lesion in relation to the body of the left sided lateral ventricle was the finding in all of the 3 patients in whom CECT head was done.{Table 2}{Table 3}{Table 4}{Figure 2}

Surgical policy

All patients underwent surgical excision. The median delay for surgical treatment from the date of diagnosis was 45 days (range: 0-108 days). GTR and NTR were achieved in eight cases each whereas tumor decompression and biopsy could be done in two cases. None of the 4 patients of EVNC could undergo a GTR. Two patients in the IVNC group required a shunt placement. The immediate post-operative MRI of the brain revealed varied volume of residual disease in 9 patients. [Figure 3] is showing post-operative residual disease in such a patient evident on an immediate post-operative CECT of brain.{Figure 3}


The post-operative histopathological examination revealed eight cases to be of atypical variant and the rest were typical neurocytoma (n = 10). The EVNC showed high MIB labeling index (median: 12.5%; range: 10-18%) and glial differentiation and all were atypical variant. The median MIB labeling index for the intra-ventricular NC cases is 3% (range: 0.5-8%). In this group, four were atypical and ten were typical. On immunohistochemical, study 15 tumors were found to be synaptophysin (SP) positive, one was SP negative. Glial fibrillary acidic protein (GFAP) was positive in two cases. Chromosome 19q deletion was found in two cases and both were EVNC.

Adjuvant radiation

All of the 17 patients who had intracranial neurocytoma received post-operative partial cranial irradiation. The radiation was planned and delivered by 3D-CRT in 10 patients [Figure 4], SRT was planned for one patient and in 7 patients radiation was planned by conventional two dimensional radiation delivery technique. In 15 patients, the prescribed dose was 56 Gy in 28 fractions over 5.5 weeks. The dose prescribed in the remaining 3 cases was 60 Gy, 54 Gy and 50 Gy respectively. The planning and dosimetric parameters of 3D-CRT are demonstrated in [Table 2].{Figure 4}

For those patients who were planned by 3D-CRT, the median dose prescribed was 56 Gy. The median number of fields used for 3D-CRT planning of intracranial neurocytomas was three. The most common beam arrangement was use of two planar parallel opposed portal with 6 megavolt (MV) photon energy and one non-coplanar superior vertex portal with 15 MV photon energy. Median HI was 1.038 and median CI was 1.33. The median brain stem dose was 52.88 Gy while the median optic chiasm dose was 40.49 Gy. The median dose received by right temporal lobe was 50.92 Gy and median dose received by the left temporal lobe was 58.85 Gy. The median dose delivered to the right and left eye and the right and left optic nerve were 2.12 Gy, 1.37 Gy, 2.22 Gy, and 3.83 Gy respectively. The PTV volume was 16.2 ml in the patient who underwent SRT.

3D-CRT planning was done to deliver localized radiation to the patient of spinal neurocytoma with the use of two fields-one anterior and one posterior. 6MV photon energy was used for both the fields. The total dose delivered was 56 Gy.

All patients tolerated treatment well. Grade II (Radiation Therapy Oncology Group acute radiation induced morbidity scoring) scalp skin toxicity was noted to be the commonest acute radiation induced morbidity and was found in 4 patients. One patient had Grade II central nervous system (CNS) morbidity while on radiation. She had the symptoms of headache, projectile vomiting and ataxia with gait imbalance. She was managed by oral steroid (dexamethasone) and acetazolamide based medical decompression therapy.

Patterns of failure and salvage therapy

One patient had both clinical and radiological evidence of local relapse. On retrospective review, she was found to have EVNC and she received adjuvant radiation to a total dose of 54 Gy after a primary near total excision. Salvage re-excision was carried out for that patient and after 7 months of surgery she is alive without any evidence of disease.

Survival analysis

All patients were alive at their final follow-up. In the evaluable patients (n = 18) after a median follow-up of 35 months (range: 3-89.8 months) the 2 year disease free survival (DFS) was noted to be 100% whereas at 3 years the DFS rate was 83% [Figure 5].{Figure 5}


Central neurocytomas (CN) are uncommon, benign (Grade-II) tumors [4] of the CNS. They are associated with favorable outcome. They consist of 0.1-0.5% of all brain tumors.[5] They can be classified in two categories: Typical and atypical according to the histological finding.

Typically young adults in their second or third decade are affected. Although cases in fourth and rarely fifth decade have been reported, the highest incidence is in the third decade (25%).[6] In our study population the median age was 23 years and more than one third of patients were below 20 years of age.

Most neurocytomas are midline supratentorial lesions straddling the lateral and third ventricles, often in relation to the foramen of Monroe and arising from the septum pellucidum, fornix, or walls of the lateral ventricles. Extra-ventricular and extra-cranial locations are also well recognized. Reported extra-ventricular locations in the nervous system include cerebral parenchyma, thalamus, cerebellum, pons, amygdala, pineal gland, retina and spinal cord.[7] In our series, 4 cases were EVNC. Three of them were found to arise from the frontal lobe, perimesencephalic area and thalamus.

In its typical form, CN present with an insidious onset of symptoms related to increased intracranial pressure. In most cases of intra-ventricular tumors the symptoms are secondary to obstructive hydrocephalus depending upon the proximity of the lesion to the foramen of Monroe.[1],[8] Common symptoms include headaches, seizures, nausea-vomiting, visual impairment, gait, bladder and memory disturbances. Lateralizing signs are uncommon in intra-ventricular location, but have been reported in cases of parenchymal lesions.[6] The duration of symptoms is generally short with symptoms usually being present for only several months by the time of presentation.[9] In our cohort, headache was the most frequent presentation followed by vomiting and visual complaints. All the patients who had a headache on presentation were found to have IVNC on imaging. Five of the patients who were having visual complaints had IVNC while one of them had EVNC (involving frontal lobe). Four patients had a complaint of hemiparesis and three of them had EVNC while one had IVNC. Seizure was a relatively uncommon symptom in our cohort and was noted in two cases. Both of them were having EVNC. In one of them the tumor was located in the frontal lobe while in the other it was located in perimesencephalic area. No patient in our cohort had memory or other higher functional deficits. None of them had symptoms related to bowel and bladder control. In our cohort, the median duration of symptoms was found to be 6 months.

Since the original description by Hassoun et al.,[2] it has generally been accepted that CN develop from the nuclei of the septum pellucidum. However, differentiation between CN and other intra-ventricular neoplasms based on histopathological appearance at the light microscopic level may be very difficult as they can all exhibit small uniform cells with perinuclear halos. Thus, the definitive diagnosis must be based on immunohistochemistry (IHC) and/or electron microscopic studies. Positivity for SP and Neuron specific enolase (NSE) and negativity for GFAP are the main IHC features of CN. Strong immunostaining for SP has been recognized as the most reliable diagnostic marker.[10] A recent report by You et al.[11] further proposed that CN cells can differentiate into neuronal cells in vivo and into glial cells in vitro. This bipotential property possibly explains the (GFAP)-immunopositive cell population observed in true CN. In our cohort, two cases were simultaneously positive for SP and GFAP suggestive of glial differentiation.

Central neurocytoma shows calcifications in up to 50% of cases.[12] It will present as a well-defined high density mass at CT scan. The presence of micro and macrocysts gives the tumor a heterogeneous appearance. Contrast enhanced CT reveals variable enhancement of the tumor: From mild-to-moderate. Most reports describe MRI appearances of CN as iso-intense or slightly hypo-intense compared to surrounding brain in T1-weighted images and hyper-intense in T2-weighted images. In both T1 and T2 weighted sequences, flow voids, which can be numerous within a lesion, are indicative of its increased vascularity while the presence of multiple foci of signal drop outs is the expression of intralesional calcifications. Sometimes multiple foci of low signal intensities are present within a lesion in proton density and T2-weighted sequences. Such abnormal signals indicate intratumoural hemorrhage.[6] They show moderate to strong enhancement after gadolinium administration.[13]

It has been estimated that neurocytomas can be completely resected in one-third to one-half of cases and it is the cornerstone of management,[14] but progression after subtotal excision and local recurrences after radiologically proven total resection are well-recognized. There is no clear association between proliferative activity and resectability. Resectability of the tumor is usually dictated by the site, size and extent of the lesion, adherence to eloquent structures, especially the fornix, vascularity of the tumor and the operator experience. There can be multiple approaches like: Standard microsurgical approaches or trans-cortical or transcallosal trans-ventricular approaches. In either approach main aims of surgery are to establish the obstructed CSF pathway, determine the histological diagnosis and accomplish maximal surgical resection with minimum risk of neurological impairment.[7] In our cohort, GTR could be achieved in eight patients, while NTR, decompression and biopsy was done in eight, one and one patients respectively. Shunt placement was required in 2 patients. Residual disease was evident in 10 patients on immediate post-operative CEMRI of brain.

Role of RT as adjuvant following GTR remains debatable since this subset of patients already have a better local control. The effect and dose of adjuvant radiation after an incomplete surgery for neurocytoma has been defined by Rades et al.[15] They reviewed all cases reported since 1982 for age, gender, resection status, total dose, dose per fraction, local control and overall survival. Additional data were obtained from the authors. Two groups were formed according to the equivalent dose in 2-Gy fractions: Group A (40.0-53.6 Gy) and Group B (54.0-62.2 Gy). In a total of 89 patients they found that at 5 years, the local control rate was 98% for Group B versus 69% for Group A. At 10 years, it was 89% versus 65% (P = 0.0066). The 5-year and 10-year survival rate was 98% for group B versus 88% for Group A (P = 0.1). They recommended a target volume of the tumor bed plus a 1.5-2.0 cm margin for adjuvant radiation after incomplete resection (ITR) of neurocytoma.

The total dose prescribed in other series (n = 6) also has been ranging from 50.4 Gy to 55.8 Gy with a median of 54 Gy.[16] In their series, 2 patients also received extended field radiation-one received whole brain radiation while the other received craniospinal radiation. The radiation dose was prescribed by use of the point calculation method or the 2D planning system. In one other series of 25 patients Hallock et al.[17] used radiation as salvage treatment after relapse. The 3 patients who received salvage radiation were treated with focal radiation to 50-54 Gy in 25-30 fractions. Leenstra et al.[18] after retrospectively analyzing 45 patients concluded that one-third of patients experienced tumor recurrence or progression regardless of initial resection. They recommended routine adjuvant RT in incompletely resected atypical tumors and in those with a high mitotic index.

Kulkarni et al.[19] studied the effect of whole brain RT post-stereotactic biopsy in eight patients. None had procedure related side-effects. Out of this one had disseminated intracranial disease at 15 months while the rest remained symptom free with good local control at 78 months of follow-up.

Finally, Rades and Schild [20] defined the role of adjuvant radiation after a comprehensive review of 438 patients. They found that after complete resection (CTR), outcome was not significantly improved by RT. After ITR, RT improved survival in typical lesions (P = 0.03) as well as atypical lesions (P = 0.05), but this survival advantage was not evident in children (P = 0.16). Local control was improved in all groups. Doses >54 Gy appeared beneficial after ITR of atypical lesions. In children, radiation dose of <50 Gy and >50 Gy were comparable. They recommended that CTR does not require post-operative RT. Following ITR, RT improves outcome. A total dose of 50-54 Gy appears sufficient for typical lesions. Atypical lesions require 56-60 Gy of adjuvant radiation.

In our institute, we irradiated a smaller volume of PTV than that recommended by Rades et al. We have omitted the concept of CTV for typical neurocytoma. Still only one patient had a local relapse in our series. The DFS rate in our series is in accordance with published world literature in spite of reducing the target volume of radiation in our study cohort. This approach needs further validation from large randomized controlled studies.

The different types of stereotactic radiosurgery (SRS) such as gamma knife surgery (GKS), linear accelerator based radiosurgery (LINAC) and Cyber knife have been used for the treatment of CNs. Cobery et al.[21] used GKS as an adjuvant therapy for residual tumor after STR as an alternative to conventional RT, in 3 cases while Hara et al.[22] introduced it in a single case. All 4 cases showed marked decrease in tumor size during a follow-up period ranging from 12 months to 99 months with minimal side effects. Recently, Yen et al.[23] studied 9 patients treated with GKS (1989-2004). These patients were followed up to 60 months' post-GKS. Among these four of nine tumors disappeared, four shrank significantly and one patient had hemorrhage jeopardizing accurate tumor volume measurement post-GKS. Based on this experience, they recommend GKS as an acceptable treatment alternative. Martin et al.[24] utilized LINAC based radiosurgery in the management of 4 patients with residual lesion after initial surgery. Two were cured; one showed considerable reduction in tumor size and the fourth remained stable. They concluded that in cases of small residual tumors or recurrences, radiosurgery allows open surgery to be avoided and is a safe and potentially effective approach.

Chemotherapy has been found beneficial in inoperable cases of central neurocytoma (CN), which showed no response to RT.[25] Multiple chemotherapeutic agents, including topetecan, cyclophosphamide, etoposide, carmustine, lomustine, vincristine and cisplatin have been tried. Brandes et al.[26] reported 3 cases of CN, who had partial tumor regression following a combination chemotherapy comprising of etoposide, cyclophosphamide and cisplatin. One patient had local recurrence in addition to cranio-spinal spread, 3 years after GTR. Three cycles of this combination resulted in partial resolution of cranial neurocytoma and complete resolution of spinal drop metastasis up to 36 months of follow-up. Second case presented with tumor recurrence 6 years after STR and CR to radiation. Third case following STR and PR to radiation presented 5 years later with recurrence. Partial resolution was noted after five cycles of chemotherapy in the second and third cases respectively. Procarbazine, CCNU, vincristine chemotherapy has also shown an advantage over RT when the recurrent tumors are too large for SRS.[27]

Experience regarding neurocytoma from Indian subcontinent has really been sparse. Experience from our own institute has been published previously.[13] It was a retrospective analysis of 20 patients over a period of 15 years (1980-1995). The mean age of the cohort was 23.1 years and the male:female ratio was 1.8:1. All were IVNC and ten of them originated from the right lateral ventricle. Only two were of atypical histology. MIB-1 labeling index (MIB-1 LI) varied from 0.1 to 3. Seven tumors were having mitoses and necrosis on histopathological examination. MIB-1 LI tended to be higher in these tumors. All of them were synaptophysin positive on immunohistochemical study. All underwent maximal safe surgery. GTR could be done in 14 cases while in 6 cases only ITR was possible. The radiation dose ranged from 40 Gy-60 Gy over 4-6 weeks and after a mean follow-up of 32 months 5 patients succumbed to complications of surgery while the rest were alive and asymptomatic. In our present series no surgical complication has been noted. This disparity points toward the modernization and adaptation of less morbid surgical techniques. The comparison between the present and past study has been shown in [Table 3].

This study gives a glimpse of the management of a rare brain tumor in a real world situation in a developing nation. Future studies should address the use of recent advances in radiation therapy, e.g. intensity modulation, image guidance or stereotactic radiation in a substantial number of patients and should find out whether evolution of radiation techniques really have an impact on local control, survival of patients with neurocytoma. As these patients are expected to survive for a long duration, we should also keep an eye on delayed effects of radiation such as neuro-cognitive deficits, growth deficit or secondary malignancies. More development in the field of genetics and molecular biology in the future era may help us to identify patients who actually need adjuvant radiation. Keeping in mind the scarcity of health resources in developing nations, the cost-benefit ratio of any such future approach should not be overlooked.


Neurocytoma is a benign neuronal tumor commonly occurring in the intra-ventricular locations though may involve extra-ventricular sites. Typical neurocytoma has a significantly better prognosis than atypical lesions. Complete resection is associated with a better outcome than incomplete surgery in all groups of neurocytomas and should be performed, whenever safely possible. We recommend post-operative radiation in the cases of atypical histology, ITR and recurrent tumors. The optimum dose prescribed should be 56 Gy in 28-30 fractions to achieve superior local control, irrespective of the surgical extent. Future studies are required to validate the concept of reduced target volume for radiation in patients of neurocytoma.


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