Elsevier

Practical Radiation Oncology

Volume 8, Issue 5, September–October 2018, Pages e275-e284
Practical Radiation Oncology

Basic Original Report
Impact of timing of radiation therapy on outcomes in atypical meningioma: A clinical audit

https://doi.org/10.1016/j.prro.2018.01.010Get rights and content

Abstract

Background

The role of early adjuvant radiation therapy (RT) in patients with atypical meningioma remains controversial. The goal of this work was to report the impact of timing of RT on outcomes in atypical meningioma.

Methods and materials

Patients of atypical meningioma were identified through electronic search of institutional database. Following surgery, RT was delivered either in upfront adjuvant setting (early adjuvant RT) or after recurrence/progression (salvage RT).

Results

There were 51 patients in the early adjuvant RT group and 30 patients in the salvage RT group. Six of 51 (12%) patients in the early adjuvant RT group recurred/progressed compared with 34 of 35 (97%) patients kept on observation after initial surgery. Thirty of these 34 patients received salvage RT, mostly after reexcision. Twelve of 30 (40%) patients recurred/progressed after salvage RT, compared with 6 of 51 (12%) patients after early adjuvant RT (P = .003). Post-RT 5-year progression-free survival was significantly better for early adjuvant RT compared to salvage RT (69% vs 28%, log-rank P < .001).

Conclusions

Within the limitations of any retrospective analysis, upfront early adjuvant RT can significantly reduce the risk of local recurrence/progression in atypical meningiomas compared with initial observation. A sizeable proportion of patients who are observed initially recur/progress over time necessitating salvage therapy; however, reexcision followed by salvage RT may not be as effective as early adjuvant RT.

Introduction

Meningiomas are the most common primary brain neoplasms in adults, composing 25% to 35% of all central nervous system tumors.1 Meningiomas have an estimated incidence of approximately 5 to 6 per 100,000 population; however, they are often detected on incidental brain imaging and autopsy.2 The World Health Organization (WHO) classification system for central nervous system tumors[3], [4], [5] recommends a 3-tiered system for meningioma grading: benign (WHO grade I), atypical (WHO grade II), and anaplastic or malignant (WHO grade III) meningiomas reflecting their natural history and expected clinical behavior. Although patients with benign meningiomas have excellent long-term outcomes[6], [7] atypical and malignant meningiomas are biologically more aggressive with resultant poorer prognosis.[6], [8] Because of subjective and varied interpretation,[9], [10], [11] however, grading of meningiomas was challenging in the past, rendering interinstitutional comparison of results difficult. The adoption of the revised WHO classification[4], [5] with clear, objective criteria for grading has reduced variability in interpretation with higher pathology concordance levels.12

Surgical excision in the form of gross total resection (GTR) remains the preferred first-line therapy for symptomatic meningiomas.[6], [7], [8] Extent of resection in meningioma has traditionally been classified using the Simpson grading system.13 Simpson grade 1 through 3 resections are considered as GTR, whereas grade 4 and 5 resections are classified as subtotal resection (STR). Benign (grade 1) meningiomas have an acceptably low rate of local recurrence/progression after GTR (approximately 7% to 12% at 5 years) and are managed expectantly with surveillance imaging, obviating the need for any radiation therapy (RT) in the postoperative adjuvant setting.[6], [14]; however, adjuvant RT has been variably advocated following STR and/or in the recurrent setting.[14], [15] In contrast, atypical meningiomas have a much higher proliferative capacity with a 7- to 8-fold increased risk of local recurrence within 5 years of initial diagnosis with surgery alone, leaving only 35% of patients disease free at 10 years[7], [8] without RT. A particularly controversial issue in the management of patients with atypical meningioma has been the role and timing of RT. Although the use of early adjuvant RT can significantly reduce the need for subsequent surgeries, this must be balanced against its potential late morbidity with resultant negative impact upon health-related quality of life.16 Morbidity of RT not only depends upon dose, but also is a function of volume of normal brain irradiated. Reported toxicities associated with wide fields without beam shaping used in the past may not necessarily apply in the modern era of high-precision techniques with tight conformation of high doses to appropriately defined target volumes. There is inconsistent and conflicting low-quality evidence regarding the role of RT in atypical meningioma, leading to widespread variation in neuro-oncologic practice. This report is a contemporary clinical audit of atypical meningiomas with a special focus on the impact of timing of RT on recurrence rates and survival in patients who were treated at an academic neuro-oncology unit in a tertiary care comprehensive cancer center.

Section snippets

Methods and materials

All patients with a histological diagnosis of atypical meningioma registering at the institute between the years 2007 and 2014 were identified through an electronic search of a prospectively maintained neuro-oncology database. The study was duly approved by the institutional ethics committee that granted waiver of informed consent owing to retrospective nature of analyses. Histologic diagnosis of grade 2 atypical meningioma as per the revised WHO 2007 classification was confirmed via dedicated

Results

Electronic search of the neuro-oncology database from 2007 through 2014 identified 86 patients with a histologically confirmed diagnosis of atypical (WHO grade II) meningioma. The demographic characteristics of this cohort are summarized in Table 1. The median age of the study cohort was 51 years (range, 13-79). Sixty-five (76%) patients had been referred for adjuvant RT after undergoing surgery outside at another institute either at initial diagnosis or after reexcision following

Discussion

This retrospective audit of patients with atypical meningioma clearly demonstrates significantly increased local recurrence rates and worse survival outcomes for patients treated with salvage RT at the time of recurrence/progression compared with patients treated with upfront adjuvant RT. This study cohort may be reflective of a higher risk group and more aggressive phenotype, possibly from a strong selection bias, wherein patients deemed at higher risk of recurrence are referred for further

Conclusions

Maximal safe resection (ideally GTR) remains the preferred front-line therapy for symptomatic meningiomas. Within the caveats and limitations inherent to any retrospective analyses, postoperative adjuvant RT in the upfront setting can significantly reduce the risk of local recurrence/progression in atypical meningiomas compared with initial observation. A sizable proportion of patients who are observed initially (regardless of the extent of resection) recur/progress over time necessitating

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    Supplementary material for this article (https://doi.org/10.1016/j.prro.2018.01.010) can be found at www.practicalradonc.org.

    Ethical approval: The study was duly approved by the Institutional Ethics Committee that also granted waiver of consent because of the retrospective nature of analyses.

    Presented in part at the 5th Quadrennial Meeting of the World Federation of Neuro-Oncologic Societies, May 2017, Zurich, Switzerland.

    Sources of support: None.

    Conflicts of interest: None.

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