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Long term outcome analysis of role of radiotherapy in Grade I meningiomas: A single centre experience from North India

Long term outcome analysis of role of radiotherapy in Grade I meningiomas: A single centre... Background: Intracranial meningiomas are the second most common tumor of the central nervous system. Grade I tumors are the most common variety of meningioma and have a benign course. Surgery is the mainstay of treatment. Radiotherapy (RT) decreases the local recurrence rates and progression in patients with subtotal excision (STE). The authors present our institute’s experience in combined modality management of 18 successive patients of Grade I meningioma. Materials and Methods: We retrospectively reviewed 18 patients of Grade I meningioma treated in our institute from 2003 to 2011. Clinical characteristics and treatment modality in form of surgery and RT were noted. Statistical analysis was done with regards to recurrence free survival and overall survival using Kaplan–Meier survival analysis. Results: The median age of the patients was 52.5 years. Seven patients were males and 11 patients were females. The median duration of symptoms was 8 months. Headache was the most common presenting symptom followed by vomiting, seizures, motor weakness and visual deficits. Five patients underwent complete excision while 13 had STE. 11 patients received early RT while 5 patients received RT at recurrence. Median RT dose delivered was 50 Gy. RT had significant effect on local control especially in subtotal resections, with overall 93.75% local control rates. Conclusions: Grade I meningiomas represent a benign neoplasm. The mainstay of therapy is gross total resection at the initial surgery. Postoperative adjuvant RT should be offered to patients with subtotal resection. Long‑term follow‑up is important as local recurrences and progression can develop years after the initial treatment. Key words: Meningioma, radiotherapy, recurrence Submission: 24‑03‑2014 Accepted: 16‑09‑2014 [1] of all primary brain tumors in adults. Meningiomas are Introduction histopathologically classified as Grade I, II, or III according to the 2000 World Health Organization (WHO) classification Intracranial meningiomas are the second most common [2] system. Ninety percent of meningiomas are WHO tumor of the central nervous system, accounting for 15–20% [3] Grade I benign tumors. Evidence in the literature comes mainly from retrospective studies carried out over long Address for correspondence: Dr. Ritesh Kumar, Department of Radiotherapy and Regional Cancer Centre, periods in which diagnostic workup changed dramatically Postgraduate Institute of Medical Education and Research, and therapeutic modalities in form of surgical techniques Chandigarh, India. and radiotherapy (RT) techniques have also evolved E‑mail: riteshkr9@gmail.com significantly. The optimal method of treatment consists of maximal safe resection (MSR). Postoperative adjuvant Access this article online RT decreases progression of tumor in incompletely Quick Response Code: [4] Website: resected tumors. It decreases the local recurrence and www.ijabmr.org progression and can be used as a adjuvant treatment [4] modality after incomplete surgical resection. We herein report our institutional experience of 18 successive DOI: 10.4103/2229-516X.157169 patients of intracranial Grade I meningiomas being treated from 2003 to 2011. International Journal of Applied and Basic Medical Research, May-Aug 2015, Vol 5, Issue 2 128 Kumar, et al.: Role of radiotherapy in Grade I meningiomas Follow‑up Materials and Methods The period between the first complaint and diagnosis was registered as symptom duration. Survival, recurrence and Patient population and initial evaluation progression information were collected through chart review, We retrospectively reviewed the patients of Grade I patient or relative contact. Response evaluation was noted meningioma from March 2003 to April 2011 treated both clinically and radiologically and RECIST criteria were in our institute. Total number of patients was 18. We [5] applied. reviewed the records of these patients to extract the following information: Age, sex, clinical symptoms, Statistical analysis histolog y, radiolog y (computed tomography/magnetic SPSS version 15 was used for statistical analysis. The Kaplan– resonance imaging [MRI]), tumor extent, and extent of Meier survival analysis was done for analyzing recurrence free surgical resection, radiation (technique, total dose, dose [6] survival (RFS) and overall survival (OS). per fraction, number of fractions), toxicity, response, recurrence, progression and death. Results Surgicop ‑ athological review Patient characteristics Operative notes were reviewed to determine intraoperative Patient characteristics are summarized in Table 1. Between suspicion of invasion, gross tumor extension into adjoining March 2003 and April 2011, 18 patients of Grade I structures, and completeness of resection. Pathology reports intracranial meningioma were registered in our department. were obtained for all patients and the tumors were graded as [2] The median age of the patients was 52.5 years and ranges per WHO histopathological grade. from 24 years to 66 years. Seven patients (38.9%) were males and 11 patients (61.1%) were females. The tumor Treatment was located at the convexity in 8 patients (44.4%), at the Surgery and RT were used in the treatment. MSR skull base in 5 patients (27.7%), parasagitally or along the was the surgical approach and RT was delivered in falx in 3 patients (16.6%), and in other locations including conventional 1.8–2 Gy per fraction. Median RT dose was the intraventricular regions or orbit in 2 patients (11.1%). 50.0 Gy which ranged from 45 to 54 Gy. RT planning The median duration of symptoms was 8 months. Headache evolved with time and expertise and patients were planned with two‑dimensional and three‑dimensional conformal was the most common presenting symptom manifesting radiotherapy (3DCRT) techniques. Six patients received in all 18 patients followed by vomiting, seizures, motor RT with two‑dimensional technique and the ten patients weakness and visual deficits. No patient had a history of received RT with 3DCRT technique. neurofibromatosis. Table 1: Patient characteristics, treatment details and outcome Age Sex Surgery Early postoperative RT Progression/recurrence T/t of progression Status 36 Female STE Yes No ‑ Alive, asymptomatic 29 Male STE Yes No ‑ Alive, asymptomatic 34 Female GTE No No ‑ Alive, asymptomatic 40 Female STE No Yes S+RT Alive, asymptomatic 60 Female STE No Yes S+RT Alive, asymptomatic 24 Male STE No Yes S+RT Progressive disease 62 Female STE Yes No ‑ Alive, asymptomatic 32 Female STE Yes No ‑ Alive, asymptomatic 62 Male STE Yes No ‑ Alive, asymptomatic 40 Female GTE No Yes S+RT Alive, asymptomatic 53 Female STE Yes No ‑ Alive, asymptomatic 66 Male GTE No Yes S+RT Alive, asymptomatic 58 Female STE Yes No ‑ Alive, asymptomatic 63 Male STE Yes No ‑ Alive, asymptomatic 56 Female GTE No No ‑ Alive, asymptomatic 49 Male STE Yes No ‑ Alive, asymptomatic 54 Female STE Yes No ‑ Alive, asymptomatic 52 Male GTE Yes No ‑ Alive, asymptomatic RT: Radiotherapy; STE: Subtotal excision; GTE: Gross total excision International Journal of Applied and Basic Medical Research, May-Aug 2015, Vol 5, Issue 2 129 Kumar, et al.: Role of radiotherapy in Grade I meningiomas Treatment details Overall survival and recurrence free survival Treatment modalities consisted of surgery and RT. All Median duration of follow‑up was 77 months (range, 15–126). patients underwent primary surgery, out of which 5 patients Mean OS was 119.7 months. underwent gross total excision (GTE) and 13 underwent subtotal excision (STE). The reasons for STE were adherence Mean RFS was 95.76 months. 5 year overall RFS was 78% to dura and adjacent brain matter, and proximity to vital and 10 year overall RFS was 60% [Figure 1]. Early adjuvant neural structures. Early postoperative RT (within 6 weeks of postoperative RT had significant impact on RFS. Mean RFS for surgery) was delivered in 11 patients and 7 patients were kept patients with early postoperative RT was 119.7 months while on regular follow‑up. 5 out of these 7 patients had recurrence for patients who did not received early postoperative RT was and received RT when they had recurrence of disease, while 58.14 months only (P = 0.2). 2 patients did not receive any RT [Table 2]. For RT planning, Total number of patients who received RT (early or after gross tumor volume (GTV) was defined as the macroscopic recurrence) was 16 and only 1 of them had progression even lesion visible on the contrast‑enhanced imaging and/or the after RT. Thus the local control rate after RT for patients in resection cavity. The planning target volume was calculated this study was 93.75%. from the GTV using a uniform three‑dimensional expansion of 1 cm. Median RT dose was 50.0 Gy which ranged from Treatment toxicity and compliance 45 to 54 Gy. There were no surgical complications in form of postoperative Clinical and radiological response deaths or wound complications. RT toxicity occurred in all After treatment completion, patients were assessed for patients in form of Grade I‑II dermatitis and there was no response both clinically and radiologically. All were Grade III or higher toxicity. All patients completed treatment asymptomatic and had significant improvement in symptoms. with no significant toxicity or treatment interruption. Eleven patients who received early postoperative adjuvant Discussion RT were alive and did not have recurrence or progression irrespective of the extent of resection. Of these eleven Intracranial meningiomas are the second most common patients, ten patients had initial STE while only one patient tumor of the central nervous system, accounting for 15–20% had initial GTE. [1] of all primary brain tumors in adults. Meningiomas are derived from nonneuroepithelial progenitor cells known as But, five out of seven patients who did not receive postoperative [3] adjuvant RT had recurrence and progression. Of these five, arachnoid cap cells. Risk factors for developing meningiomas three had initial STE only while two had initial GTE. All the range from hereditary syndromes, chromosomal deletions, [3] five recurrence cases were managed with re‑excision and and previously ionizing RT. No patients in our series had any further localized RT. Four of them are alive with clinical history of these risk factors. The incidence of these tumors and radiologically free from disease while further disease increases with age and is most commonly seen in sixth and [7] progression was seen in 1 patient. seventh decades of life. The median age of patients in our series was 52.5 years. Table 2: Treatment details Treatment modality Number of patients (%) Extent of resection Complete (GTE) 5 (27.8) Subtotal (STE) 13 (72.2) Initial treatment approach Surgery only 7 (38.9) Surgery+RT 11 (61.1) RT Adjuvant (early) 11 (61.1) After progression 5 (27.7) No RT 2 (11.1) Dose (median) 50.0 Gy Dose (range) 45‑54 Gy RT modality Two‑dimensional 6 Three‑dimensional 10 RT: Radiotherapy; STE: Subtotal excision; GTE: Gross total excision Figure 1: Kaplan–Meier curve showing recurrence free survival International Journal of Applied and Basic Medical Research, May-Aug 2015, Vol 5, Issue 2 130 Kumar, et al.: Role of radiotherapy in Grade I meningiomas Histologically they are classified as Grade I, II, or III according are not amenable to surgery and to those who are medically [2] [12] to the 2000 WHO classification system. Ninety percent of inoperable. [3] meningiomas are WHO Grade I benign tumors. Most of the Patients with Grade I benign diseases have a favorable Grade I meningiomas asymptomatic and discovered incidentally, [3] long‑term survival, which can increase to more than 90% thereby earning the name incidentaloma. However, if the by adding RT. Condra et al. examined 229 patients treated meningioma growth causes secondary compression of vital with external‑beam RT for benign and atypical disease structures, then the patient becomes symptomatic. The most at the University of Florida between 1964 and 1992. The common locations of meningiomas, in descending order of 10‑year local control improved to 90% with the addition of frequency, are convexity (19–34%), parasagittal (18–25%), RT, compared with 80% and 40% in those receiving gross sphenoid and middle cranial fossa (17–25%), frontal base (10%) [13] total and subtotal resection alone, respectively. Brell et al. and posterior fossa (9–1 5%), cerebellar convexity (5%), treated 30 cavernous sinus meningiomas with fractionated cerebellopontine angle (2–4%), intraventricular (1–5%), and [8] RT in Barcelona, Spain, between 1997 and 2001. Patients clivus (1%). In our series, the most common location was were treated with a once‑daily fraction of 2 Gy to a median the convexity (44.4%) followed by the skull base (27.7%) [14] of 52 Gy. The actuarial local PFS was 93% at 4 years. In our and parasagital (16.6%). The clinical presentation in these series, RFS was significantly increased with addition of early patients is determined by tumor location and size. Typical postoperative adjuvant RT which was more effective in patients clinical presentations have been extensively described in the with subtotal resection. Of the 13 patients who had subtotal literature, the most common of which are headache, seizures, resection, 3 did not receive RT and all three had progression. visual symptoms, motor weakness and mental status changes. Overall the local control rate after RT for patients in our [9] The optimal method of treatment consists of MSR. study was 93.75%. Surgery offers immediate relief of mass effect and allows Radiosurgery may be used for patients who have recurrent histopathological confirmation of diagnosis. Gross total resection (GTR) is preferred approach but the frequent or residual tumors or as a primary treatment in patients association with vital neural structures often makes GTR unwilling or unable to undergo surgery and who possess a challenging. In our series, only 27.7% of patients underwent lesion with the typical imaging characteristics of a meningioma. complete (GTR) surgical excision while the rest 72.3% of Radiosurgery for meningiomas is usually performed with the [15] patients underwent STE only. The reasons for STE were gamma knife (GK). Modified linear accelarators or proton adherence to dura and adjacent brain matter, and proximity beam can also be used. This method of treatment is designed to vital neural structures. The extent of surgical resection is for smaller tumors ≤3 cm, located more than 3 mm from [16] the most important factor in the prevention of recurrence. radiosensitive structures, such as the optic nerve. Stafford In 1957, Simpson retrospectively reviewed the postoperative et al. treated 178 patients with radiosurgery at the Mayo course of 265 patients who had meningiomas, 55 of whom Clinic. The 5‑year cause‑specific survival rate was 100%, and [17] experienced recurrences (21%). Recurrence rates were higher local control was 98%. Kreil et al. treated benign skull‑base [9] in patients with subtotal resection as compared to GTR. meningiomas with GK radiosurgery and reported 5 year and [18] Mathiesen et al. also reported decreased recurrence rates 10 year PFS of 98.5% and 97.2%, respectively. Hasegawa [10] with increasing extensiveness of resection. Soyuer et al. et al. reported on 115 patients with benign cavernous sinus reported 92 patients treated at M. D. Anderson Hospital and meningiomas treated with GK radiosurgery. The local control [19] found that patients who had a GTR had a favourable PFS at rates at 5 and 10 years were 94% and 92%, respectively. 5 years of 77% compared to 52% in patients who received a [4] The present literature and evidence argues in favor of early subtotal resection. [4] RT in patients with subtotal resections. In our series also, 3 However, their anatomic location near vital neural structures out of 13 patients of initial subtotal resection had progression and at the base of skull makes complete resection of the tumor when early RT was not given. One main argument commonly difficult and for that reason, a subtotal resection and adjuvant used against early RT was the development of neurocognitive RT is frequently the optimal treatment regimen. Because of deficits. However, with modern RT techniques the risk of RT the well‑circumscribed nature and slow progression rate of related neurocognitive deficits is very low because of sparing [20,21] WHO Grade I tumors, surgery is a reasonable option for of normal tissues. symptomatic lesions that are completely resectable with acceptable morbidity. Otherwise, subtotal resection followed Extent of surgical excision and early RT are important [11] [22,23] by postoperative RT is an effective treatment option. prognostic factor in local control. In our series also, Definitive RT may be offered to patients with tumors that early adjuvant RT had a significant impact on local control International Journal of Applied and Basic Medical Research, May-Aug 2015, Vol 5, Issue 2 131 Kumar, et al.: Role of radiotherapy in Grade I meningiomas 12. Rockhill J, Mrugala M, Chamberlain MC. Intracranial meningiomas: An and recurrence. Long term follow‑up with periodic MRI and overview of diagnosis and treatment. Neurosurg Focus 2007;23:E1. thorough neurological examination is recommended because 13. Condra KS, Buatti JM, Mendenhall WM, Friedman WA, Marcus RB Jr, meningiomas may recur years after treatment. Rhoton AL. Benign meningiomas: Primary treatment selection affects survival. Int J Radiat Oncol Biol Phys 1997;39:427‑36. The management of Grade I meningiomas is a paradigm of 14. Brell M, Villà S, Teixidor P, Lucas A, Ferrán E, Marín S, et al. Fractionated stereotactic radiotherapy in the treatment of exclusive cavernous sinus cooperation between clinicians, surgeons and pathologists from meningioma: Functional outcome, local control, and tolerance. Surg establishing diagnosis to organizing the therapeutic strategy. Neurol 2006;65:28‑33. With new techniques, there is a significant improvement of 15. Kondziolka D, Lunsford LD, Coffey RJ, Flickinger JC. Stereotactic therapeutic standard and meningiomas represent a model of radiosurgery of meningiomas. J Neurosurg 1991;74:552‑9. 16. Hamm K, Henzel M, Gross MW, Surber G, Kleinert G, Engenhart‑Cabillic R. therapeutic implementation and achievement in oncology. Radiosurgery/stereotactic radiotherapy in the therapeutical concept Novel strategies including advanced RT techniques such as for skull base meningiomas. Zentralbl Neurochir 2008;69:14‑21. IMRT, SRS, SRT and proton therapy should be prospectively 17. Stafford SL, Pollock BE, Foote RL, Link MJ, Gorman DA, Schomberg PJ, et al. investigated Meningioma radiosurgery: Tumor control, outcomes, and complications among 190 consecutive patients. Neurosurgery 2001;49:1029‑37. 18. Kreil W, Luggin J, Fuchs I, Weigl V, Eustacchio S, Papaefthymiou G. Long References term experience of gamma knife radiosurgery for benign skull base meningiomas. J Neurol Neurosurg Psychiatry 2005;76:1425‑30. 1. Bondy M, Ligon BL. Epidemiology and etiology of intracranial 19. Hasegawa T, Kida Y, Yoshimoto M, Koike J, Iizuka H, Ishii D. Long‑term meningiomas: A review. J Neurooncol 1996;29:197‑205. outcomes of Gamma Knife surgery for cavernous sinus meningioma. 2. Moradi A, Semnani V, Djam H, Tajodini A, Zali AR, Ghaemi K, et al. J Neurosurg 2007;107:745‑51. Pathodiagnostic parameters for meningioma grading. J Clin Neurosci 20. van Nieuwenhuizen D, Klein M, Stalpers LJ, Leenstra S, Heimans JJ, 2008;15:1370‑5. Reijneveld JC. Differential effect of surgery and radiotherapy on 3. Marosi C, Hassler M, Roessler K, Reni M, Sant M, Mazza E, et al. neurocognitive functioning and health‑related quality of life in WHO Meningioma. Crit Rev Oncol Hematol 2008;67:153‑71. grade I meningioma patients. J Neurooncol 2007;84:271‑8. 4. Soyuer S, Chang EL, Selek U, Shi W, Maor MH, DeMonte F. Radiotherapy 21. Dijkstra M, van Nieuwenhuizen D, Stalpers LJ, Wumkes M, Waagemans M, after surgery for benign cerebral meningioma. Radiother Oncol Vandertop WP, et al. Late neurocognitive sequelae in patients with WHO 2004;71:85‑90. grade I meningioma. J Neurol Neurosurg Psychiatry 2009;80:910‑5. 5. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, 22. Mirimanoff RO, Dosoretz DE, Linggood RM, Ojemann RG, Martuza RL. et al. New response evaluation criteria in solid tumours: Revised RECIST Meningioma: Analysis of recurrence and progression following guideline (version 1.1). Eur J Cancer 2009;45:228‑47. neurosurgical resection. J Neurosurg 1985;62:18‑24. 6. Kaplan EL, Meier P. Nonparametric estimation from incomplete 23. Ayerbe J, Lobato RD, de la Cruz J, Alday R, Rivas JJ, Gómez PA, observations. J Am Stat Assoc 1958;53:457‑81. et al. Risk factors predicting recurrence in patients operated on for 7. Whittle IR, Smith C, Navoo P, Collie D. Meningiomas. Lancet intracranial meningioma. A multivariate analysis. Acta Neurochir (Wien) 2004;363:1535‑43. 1999;141:921‑32. 8. Buetow MP, Buetow PC, Smirniotopoulos JG. Typical, atypical, and misleading features in meningioma. Radiographics 1991;11:1087‑106. How to cite this article: Kumar R, Kumar N, Khosla D, Gupta SK, Radotra BD, 9. Simpson D. The recurrence of intracranial meningiomas after surgical Sharma SC. Long term outcome analysis of role of radiotherapy in Grade I treatment. J Neurol Neurosurg Psychiatry 1957;20:22‑39. meningiomas: A single centre experience from North India. Int J App Basic 10. Mathiesen T, Lindquist C, Kihlström L, Karlsson B. Recurrence of cranial Med Res 2015;5:128-32. base meningiomas. Neurosurgery 1996;39:2‑7. 11. Chamberlain MC. Intracerebral Meningiomas. Curr Treat Options Neurol Source of Support: Nil. Conflict of Interest: None declared. 2004;6:297‑305. International Journal of Applied and Basic Medical Research, May-Aug 2015, Vol 5, Issue 2 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Journal of Applied and Basic Medical Research Pubmed Central

Long term outcome analysis of role of radiotherapy in Grade I meningiomas: A single centre experience from North India

International Journal of Applied and Basic Medical Research , Volume 5 (2) – Nov 1, 168

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Copyright: © International Journal of Applied and Basic Medical Research
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2229-516X
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2248-9606
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10.4103/2229-516X.157169
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Abstract

Background: Intracranial meningiomas are the second most common tumor of the central nervous system. Grade I tumors are the most common variety of meningioma and have a benign course. Surgery is the mainstay of treatment. Radiotherapy (RT) decreases the local recurrence rates and progression in patients with subtotal excision (STE). The authors present our institute’s experience in combined modality management of 18 successive patients of Grade I meningioma. Materials and Methods: We retrospectively reviewed 18 patients of Grade I meningioma treated in our institute from 2003 to 2011. Clinical characteristics and treatment modality in form of surgery and RT were noted. Statistical analysis was done with regards to recurrence free survival and overall survival using Kaplan–Meier survival analysis. Results: The median age of the patients was 52.5 years. Seven patients were males and 11 patients were females. The median duration of symptoms was 8 months. Headache was the most common presenting symptom followed by vomiting, seizures, motor weakness and visual deficits. Five patients underwent complete excision while 13 had STE. 11 patients received early RT while 5 patients received RT at recurrence. Median RT dose delivered was 50 Gy. RT had significant effect on local control especially in subtotal resections, with overall 93.75% local control rates. Conclusions: Grade I meningiomas represent a benign neoplasm. The mainstay of therapy is gross total resection at the initial surgery. Postoperative adjuvant RT should be offered to patients with subtotal resection. Long‑term follow‑up is important as local recurrences and progression can develop years after the initial treatment. Key words: Meningioma, radiotherapy, recurrence Submission: 24‑03‑2014 Accepted: 16‑09‑2014 [1] of all primary brain tumors in adults. Meningiomas are Introduction histopathologically classified as Grade I, II, or III according to the 2000 World Health Organization (WHO) classification Intracranial meningiomas are the second most common [2] system. Ninety percent of meningiomas are WHO tumor of the central nervous system, accounting for 15–20% [3] Grade I benign tumors. Evidence in the literature comes mainly from retrospective studies carried out over long Address for correspondence: Dr. Ritesh Kumar, Department of Radiotherapy and Regional Cancer Centre, periods in which diagnostic workup changed dramatically Postgraduate Institute of Medical Education and Research, and therapeutic modalities in form of surgical techniques Chandigarh, India. and radiotherapy (RT) techniques have also evolved E‑mail: riteshkr9@gmail.com significantly. The optimal method of treatment consists of maximal safe resection (MSR). Postoperative adjuvant Access this article online RT decreases progression of tumor in incompletely Quick Response Code: [4] Website: resected tumors. It decreases the local recurrence and www.ijabmr.org progression and can be used as a adjuvant treatment [4] modality after incomplete surgical resection. We herein report our institutional experience of 18 successive DOI: 10.4103/2229-516X.157169 patients of intracranial Grade I meningiomas being treated from 2003 to 2011. International Journal of Applied and Basic Medical Research, May-Aug 2015, Vol 5, Issue 2 128 Kumar, et al.: Role of radiotherapy in Grade I meningiomas Follow‑up Materials and Methods The period between the first complaint and diagnosis was registered as symptom duration. Survival, recurrence and Patient population and initial evaluation progression information were collected through chart review, We retrospectively reviewed the patients of Grade I patient or relative contact. Response evaluation was noted meningioma from March 2003 to April 2011 treated both clinically and radiologically and RECIST criteria were in our institute. Total number of patients was 18. We [5] applied. reviewed the records of these patients to extract the following information: Age, sex, clinical symptoms, Statistical analysis histolog y, radiolog y (computed tomography/magnetic SPSS version 15 was used for statistical analysis. The Kaplan– resonance imaging [MRI]), tumor extent, and extent of Meier survival analysis was done for analyzing recurrence free surgical resection, radiation (technique, total dose, dose [6] survival (RFS) and overall survival (OS). per fraction, number of fractions), toxicity, response, recurrence, progression and death. Results Surgicop ‑ athological review Patient characteristics Operative notes were reviewed to determine intraoperative Patient characteristics are summarized in Table 1. Between suspicion of invasion, gross tumor extension into adjoining March 2003 and April 2011, 18 patients of Grade I structures, and completeness of resection. Pathology reports intracranial meningioma were registered in our department. were obtained for all patients and the tumors were graded as [2] The median age of the patients was 52.5 years and ranges per WHO histopathological grade. from 24 years to 66 years. Seven patients (38.9%) were males and 11 patients (61.1%) were females. The tumor Treatment was located at the convexity in 8 patients (44.4%), at the Surgery and RT were used in the treatment. MSR skull base in 5 patients (27.7%), parasagitally or along the was the surgical approach and RT was delivered in falx in 3 patients (16.6%), and in other locations including conventional 1.8–2 Gy per fraction. Median RT dose was the intraventricular regions or orbit in 2 patients (11.1%). 50.0 Gy which ranged from 45 to 54 Gy. RT planning The median duration of symptoms was 8 months. Headache evolved with time and expertise and patients were planned with two‑dimensional and three‑dimensional conformal was the most common presenting symptom manifesting radiotherapy (3DCRT) techniques. Six patients received in all 18 patients followed by vomiting, seizures, motor RT with two‑dimensional technique and the ten patients weakness and visual deficits. No patient had a history of received RT with 3DCRT technique. neurofibromatosis. Table 1: Patient characteristics, treatment details and outcome Age Sex Surgery Early postoperative RT Progression/recurrence T/t of progression Status 36 Female STE Yes No ‑ Alive, asymptomatic 29 Male STE Yes No ‑ Alive, asymptomatic 34 Female GTE No No ‑ Alive, asymptomatic 40 Female STE No Yes S+RT Alive, asymptomatic 60 Female STE No Yes S+RT Alive, asymptomatic 24 Male STE No Yes S+RT Progressive disease 62 Female STE Yes No ‑ Alive, asymptomatic 32 Female STE Yes No ‑ Alive, asymptomatic 62 Male STE Yes No ‑ Alive, asymptomatic 40 Female GTE No Yes S+RT Alive, asymptomatic 53 Female STE Yes No ‑ Alive, asymptomatic 66 Male GTE No Yes S+RT Alive, asymptomatic 58 Female STE Yes No ‑ Alive, asymptomatic 63 Male STE Yes No ‑ Alive, asymptomatic 56 Female GTE No No ‑ Alive, asymptomatic 49 Male STE Yes No ‑ Alive, asymptomatic 54 Female STE Yes No ‑ Alive, asymptomatic 52 Male GTE Yes No ‑ Alive, asymptomatic RT: Radiotherapy; STE: Subtotal excision; GTE: Gross total excision International Journal of Applied and Basic Medical Research, May-Aug 2015, Vol 5, Issue 2 129 Kumar, et al.: Role of radiotherapy in Grade I meningiomas Treatment details Overall survival and recurrence free survival Treatment modalities consisted of surgery and RT. All Median duration of follow‑up was 77 months (range, 15–126). patients underwent primary surgery, out of which 5 patients Mean OS was 119.7 months. underwent gross total excision (GTE) and 13 underwent subtotal excision (STE). The reasons for STE were adherence Mean RFS was 95.76 months. 5 year overall RFS was 78% to dura and adjacent brain matter, and proximity to vital and 10 year overall RFS was 60% [Figure 1]. Early adjuvant neural structures. Early postoperative RT (within 6 weeks of postoperative RT had significant impact on RFS. Mean RFS for surgery) was delivered in 11 patients and 7 patients were kept patients with early postoperative RT was 119.7 months while on regular follow‑up. 5 out of these 7 patients had recurrence for patients who did not received early postoperative RT was and received RT when they had recurrence of disease, while 58.14 months only (P = 0.2). 2 patients did not receive any RT [Table 2]. For RT planning, Total number of patients who received RT (early or after gross tumor volume (GTV) was defined as the macroscopic recurrence) was 16 and only 1 of them had progression even lesion visible on the contrast‑enhanced imaging and/or the after RT. Thus the local control rate after RT for patients in resection cavity. The planning target volume was calculated this study was 93.75%. from the GTV using a uniform three‑dimensional expansion of 1 cm. Median RT dose was 50.0 Gy which ranged from Treatment toxicity and compliance 45 to 54 Gy. There were no surgical complications in form of postoperative Clinical and radiological response deaths or wound complications. RT toxicity occurred in all After treatment completion, patients were assessed for patients in form of Grade I‑II dermatitis and there was no response both clinically and radiologically. All were Grade III or higher toxicity. All patients completed treatment asymptomatic and had significant improvement in symptoms. with no significant toxicity or treatment interruption. Eleven patients who received early postoperative adjuvant Discussion RT were alive and did not have recurrence or progression irrespective of the extent of resection. Of these eleven Intracranial meningiomas are the second most common patients, ten patients had initial STE while only one patient tumor of the central nervous system, accounting for 15–20% had initial GTE. [1] of all primary brain tumors in adults. Meningiomas are derived from nonneuroepithelial progenitor cells known as But, five out of seven patients who did not receive postoperative [3] adjuvant RT had recurrence and progression. Of these five, arachnoid cap cells. Risk factors for developing meningiomas three had initial STE only while two had initial GTE. All the range from hereditary syndromes, chromosomal deletions, [3] five recurrence cases were managed with re‑excision and and previously ionizing RT. No patients in our series had any further localized RT. Four of them are alive with clinical history of these risk factors. The incidence of these tumors and radiologically free from disease while further disease increases with age and is most commonly seen in sixth and [7] progression was seen in 1 patient. seventh decades of life. The median age of patients in our series was 52.5 years. Table 2: Treatment details Treatment modality Number of patients (%) Extent of resection Complete (GTE) 5 (27.8) Subtotal (STE) 13 (72.2) Initial treatment approach Surgery only 7 (38.9) Surgery+RT 11 (61.1) RT Adjuvant (early) 11 (61.1) After progression 5 (27.7) No RT 2 (11.1) Dose (median) 50.0 Gy Dose (range) 45‑54 Gy RT modality Two‑dimensional 6 Three‑dimensional 10 RT: Radiotherapy; STE: Subtotal excision; GTE: Gross total excision Figure 1: Kaplan–Meier curve showing recurrence free survival International Journal of Applied and Basic Medical Research, May-Aug 2015, Vol 5, Issue 2 130 Kumar, et al.: Role of radiotherapy in Grade I meningiomas Histologically they are classified as Grade I, II, or III according are not amenable to surgery and to those who are medically [2] [12] to the 2000 WHO classification system. Ninety percent of inoperable. [3] meningiomas are WHO Grade I benign tumors. Most of the Patients with Grade I benign diseases have a favorable Grade I meningiomas asymptomatic and discovered incidentally, [3] long‑term survival, which can increase to more than 90% thereby earning the name incidentaloma. However, if the by adding RT. Condra et al. examined 229 patients treated meningioma growth causes secondary compression of vital with external‑beam RT for benign and atypical disease structures, then the patient becomes symptomatic. The most at the University of Florida between 1964 and 1992. The common locations of meningiomas, in descending order of 10‑year local control improved to 90% with the addition of frequency, are convexity (19–34%), parasagittal (18–25%), RT, compared with 80% and 40% in those receiving gross sphenoid and middle cranial fossa (17–25%), frontal base (10%) [13] total and subtotal resection alone, respectively. Brell et al. and posterior fossa (9–1 5%), cerebellar convexity (5%), treated 30 cavernous sinus meningiomas with fractionated cerebellopontine angle (2–4%), intraventricular (1–5%), and [8] RT in Barcelona, Spain, between 1997 and 2001. Patients clivus (1%). In our series, the most common location was were treated with a once‑daily fraction of 2 Gy to a median the convexity (44.4%) followed by the skull base (27.7%) [14] of 52 Gy. The actuarial local PFS was 93% at 4 years. In our and parasagital (16.6%). The clinical presentation in these series, RFS was significantly increased with addition of early patients is determined by tumor location and size. Typical postoperative adjuvant RT which was more effective in patients clinical presentations have been extensively described in the with subtotal resection. Of the 13 patients who had subtotal literature, the most common of which are headache, seizures, resection, 3 did not receive RT and all three had progression. visual symptoms, motor weakness and mental status changes. Overall the local control rate after RT for patients in our [9] The optimal method of treatment consists of MSR. study was 93.75%. Surgery offers immediate relief of mass effect and allows Radiosurgery may be used for patients who have recurrent histopathological confirmation of diagnosis. Gross total resection (GTR) is preferred approach but the frequent or residual tumors or as a primary treatment in patients association with vital neural structures often makes GTR unwilling or unable to undergo surgery and who possess a challenging. In our series, only 27.7% of patients underwent lesion with the typical imaging characteristics of a meningioma. complete (GTR) surgical excision while the rest 72.3% of Radiosurgery for meningiomas is usually performed with the [15] patients underwent STE only. The reasons for STE were gamma knife (GK). Modified linear accelarators or proton adherence to dura and adjacent brain matter, and proximity beam can also be used. This method of treatment is designed to vital neural structures. The extent of surgical resection is for smaller tumors ≤3 cm, located more than 3 mm from [16] the most important factor in the prevention of recurrence. radiosensitive structures, such as the optic nerve. Stafford In 1957, Simpson retrospectively reviewed the postoperative et al. treated 178 patients with radiosurgery at the Mayo course of 265 patients who had meningiomas, 55 of whom Clinic. The 5‑year cause‑specific survival rate was 100%, and [17] experienced recurrences (21%). Recurrence rates were higher local control was 98%. Kreil et al. treated benign skull‑base [9] in patients with subtotal resection as compared to GTR. meningiomas with GK radiosurgery and reported 5 year and [18] Mathiesen et al. also reported decreased recurrence rates 10 year PFS of 98.5% and 97.2%, respectively. Hasegawa [10] with increasing extensiveness of resection. Soyuer et al. et al. reported on 115 patients with benign cavernous sinus reported 92 patients treated at M. D. Anderson Hospital and meningiomas treated with GK radiosurgery. The local control [19] found that patients who had a GTR had a favourable PFS at rates at 5 and 10 years were 94% and 92%, respectively. 5 years of 77% compared to 52% in patients who received a [4] The present literature and evidence argues in favor of early subtotal resection. [4] RT in patients with subtotal resections. In our series also, 3 However, their anatomic location near vital neural structures out of 13 patients of initial subtotal resection had progression and at the base of skull makes complete resection of the tumor when early RT was not given. One main argument commonly difficult and for that reason, a subtotal resection and adjuvant used against early RT was the development of neurocognitive RT is frequently the optimal treatment regimen. Because of deficits. However, with modern RT techniques the risk of RT the well‑circumscribed nature and slow progression rate of related neurocognitive deficits is very low because of sparing [20,21] WHO Grade I tumors, surgery is a reasonable option for of normal tissues. symptomatic lesions that are completely resectable with acceptable morbidity. Otherwise, subtotal resection followed Extent of surgical excision and early RT are important [11] [22,23] by postoperative RT is an effective treatment option. prognostic factor in local control. In our series also, Definitive RT may be offered to patients with tumors that early adjuvant RT had a significant impact on local control International Journal of Applied and Basic Medical Research, May-Aug 2015, Vol 5, Issue 2 131 Kumar, et al.: Role of radiotherapy in Grade I meningiomas 12. Rockhill J, Mrugala M, Chamberlain MC. Intracranial meningiomas: An and recurrence. Long term follow‑up with periodic MRI and overview of diagnosis and treatment. Neurosurg Focus 2007;23:E1. thorough neurological examination is recommended because 13. Condra KS, Buatti JM, Mendenhall WM, Friedman WA, Marcus RB Jr, meningiomas may recur years after treatment. Rhoton AL. Benign meningiomas: Primary treatment selection affects survival. Int J Radiat Oncol Biol Phys 1997;39:427‑36. The management of Grade I meningiomas is a paradigm of 14. Brell M, Villà S, Teixidor P, Lucas A, Ferrán E, Marín S, et al. Fractionated stereotactic radiotherapy in the treatment of exclusive cavernous sinus cooperation between clinicians, surgeons and pathologists from meningioma: Functional outcome, local control, and tolerance. Surg establishing diagnosis to organizing the therapeutic strategy. Neurol 2006;65:28‑33. With new techniques, there is a significant improvement of 15. Kondziolka D, Lunsford LD, Coffey RJ, Flickinger JC. Stereotactic therapeutic standard and meningiomas represent a model of radiosurgery of meningiomas. J Neurosurg 1991;74:552‑9. 16. Hamm K, Henzel M, Gross MW, Surber G, Kleinert G, Engenhart‑Cabillic R. therapeutic implementation and achievement in oncology. Radiosurgery/stereotactic radiotherapy in the therapeutical concept Novel strategies including advanced RT techniques such as for skull base meningiomas. Zentralbl Neurochir 2008;69:14‑21. IMRT, SRS, SRT and proton therapy should be prospectively 17. Stafford SL, Pollock BE, Foote RL, Link MJ, Gorman DA, Schomberg PJ, et al. investigated Meningioma radiosurgery: Tumor control, outcomes, and complications among 190 consecutive patients. Neurosurgery 2001;49:1029‑37. 18. Kreil W, Luggin J, Fuchs I, Weigl V, Eustacchio S, Papaefthymiou G. Long References term experience of gamma knife radiosurgery for benign skull base meningiomas. J Neurol Neurosurg Psychiatry 2005;76:1425‑30. 1. Bondy M, Ligon BL. Epidemiology and etiology of intracranial 19. Hasegawa T, Kida Y, Yoshimoto M, Koike J, Iizuka H, Ishii D. Long‑term meningiomas: A review. J Neurooncol 1996;29:197‑205. outcomes of Gamma Knife surgery for cavernous sinus meningioma. 2. Moradi A, Semnani V, Djam H, Tajodini A, Zali AR, Ghaemi K, et al. J Neurosurg 2007;107:745‑51. Pathodiagnostic parameters for meningioma grading. J Clin Neurosci 20. van Nieuwenhuizen D, Klein M, Stalpers LJ, Leenstra S, Heimans JJ, 2008;15:1370‑5. Reijneveld JC. Differential effect of surgery and radiotherapy on 3. Marosi C, Hassler M, Roessler K, Reni M, Sant M, Mazza E, et al. neurocognitive functioning and health‑related quality of life in WHO Meningioma. Crit Rev Oncol Hematol 2008;67:153‑71. grade I meningioma patients. J Neurooncol 2007;84:271‑8. 4. Soyuer S, Chang EL, Selek U, Shi W, Maor MH, DeMonte F. Radiotherapy 21. Dijkstra M, van Nieuwenhuizen D, Stalpers LJ, Wumkes M, Waagemans M, after surgery for benign cerebral meningioma. Radiother Oncol Vandertop WP, et al. Late neurocognitive sequelae in patients with WHO 2004;71:85‑90. grade I meningioma. J Neurol Neurosurg Psychiatry 2009;80:910‑5. 5. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, 22. Mirimanoff RO, Dosoretz DE, Linggood RM, Ojemann RG, Martuza RL. et al. New response evaluation criteria in solid tumours: Revised RECIST Meningioma: Analysis of recurrence and progression following guideline (version 1.1). Eur J Cancer 2009;45:228‑47. neurosurgical resection. J Neurosurg 1985;62:18‑24. 6. Kaplan EL, Meier P. Nonparametric estimation from incomplete 23. Ayerbe J, Lobato RD, de la Cruz J, Alday R, Rivas JJ, Gómez PA, observations. J Am Stat Assoc 1958;53:457‑81. et al. Risk factors predicting recurrence in patients operated on for 7. Whittle IR, Smith C, Navoo P, Collie D. Meningiomas. Lancet intracranial meningioma. A multivariate analysis. Acta Neurochir (Wien) 2004;363:1535‑43. 1999;141:921‑32. 8. Buetow MP, Buetow PC, Smirniotopoulos JG. Typical, atypical, and misleading features in meningioma. Radiographics 1991;11:1087‑106. How to cite this article: Kumar R, Kumar N, Khosla D, Gupta SK, Radotra BD, 9. Simpson D. The recurrence of intracranial meningiomas after surgical Sharma SC. Long term outcome analysis of role of radiotherapy in Grade I treatment. J Neurol Neurosurg Psychiatry 1957;20:22‑39. meningiomas: A single centre experience from North India. Int J App Basic 10. Mathiesen T, Lindquist C, Kihlström L, Karlsson B. Recurrence of cranial Med Res 2015;5:128-32. base meningiomas. Neurosurgery 1996;39:2‑7. 11. Chamberlain MC. Intracerebral Meningiomas. Curr Treat Options Neurol Source of Support: Nil. Conflict of Interest: None declared. 2004;6:297‑305. International Journal of Applied and Basic Medical Research, May-Aug 2015, Vol 5, Issue 2

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International Journal of Applied and Basic Medical ResearchPubmed Central

Published: Nov 1, 168

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