Spot-Scanning based proton radiation therapy for complex benign, atypical, and anaplastic meningiomas: 5 year results from the Paul Scherrer Institute (PSI)

Reporter: Arpi Thukral, MD MPH
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 13, 2011

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Presenter/Author:Ralf Schneider, MD
Presenter's Affiliation:Center for Proton Therapy, Paul Scherrer Institute (PSI), Switzerland

Background

  • Meningiomas are the most common non-glial brain tumors, which are slow growing and extra-axial. They arise from the arachnoid cap cells of the central nervous system.
  • The WHO classification system is widely used to characterize the histologic behavior of meningiomas. Although the majority of meningiomas are benign (WHO grade I), 7-10% are classified as atypical and anaplastic meningiomas (WHO grade II/III, respectively).
  • For benign meningiomas, if resectable, surgery is the mainstay of treatment and results in local control rates of >70% in many previous studies. If subtotal resection is performed, local recurrence rates are much higher, and post-operative radiation with either external beam photon therapy, IMRT, or stereotactic radiosurgery is generally recommended.
    • If the tumor is inoperable, or if there are contraindications to surgery, definitive radiation can be delivered with 5-year local tumor control rates in 80% range, according to published data.
  • Local control rates for atypical and anaplastic meningiomas are much lower than that for benign tumors, and post-operative radiation therapy is highly recommended to reduce risk of recurrence in these patients.
  • During radiation of meningiomas, dose has to be very precisely delivered to spare normal brain and critical normal structures. Volumes of radiation for complex benign or high-grade meningiomas can often be quite large due to extent of tumor, and present a challenge in sparing organs at risk.
  • Proton beam radiation therapy (PRT) offers a potential advantage is this disease site due to its increased conformality and homogeneous dose distribution. This may allow better sparing of normal tissues such as the optic pathway, brainstem and pituitary gland.
  • The purpose of this study was to evaluate the long-term clinical results of proton radiation in patients with difficult to treat intracranial meningiomas, using a spot-scanning technique at the Paul Scherrer Institute (PSI) in Switzerland.

Materials and Methods

  • This study was retrospective analysis of 39 patients with meningioma that were treated at PSI with proton therapy using a spot-scanning technique at PSI between July 1997 and January 2010.
  • Patient characteristics:
    • 29 patients (74%) had complex benign meningiomas (24/29 were biopsy-proven)
    • 10 patients (16%) had atypical or anaplastic meningiomas.
    • 32 patients (82%) had skull base involvement.
    • 32 patients treated for primary disease (PRT only in 8 patients and post-operative PRT in 24 patients).
    • All patients except 1 had pathology reviewed according to the latest WHO Classification.
    • Mean age: 48.3 years +/- 17.9 years.
    • Female to male ratio: 3.3.
    • 3 patients had a history of prior irradiation.
  • Radiation:
    • GTV volume ranged from 0.76-546.5 cc (median 21.5 cc)
    • All patients were positioned with a bite bloc or head mask.
    • Prescribed median dose: 56.0 Gy; range 52.2 -66.6 Gy)
      • 55 Gy for benign (RBE); range 52.2-64 Gy
      • 60.8 Gy for higher grade histology (RBE); range 54.0-66.6 Gy
      • 1.8-2 Gy (RBE)/ fraction
      • RBE=1.1
  • OAR constraints:
    • 54.0/63.0 Gy to center and surface of brainstem, respectively
    • 56 Gy to optic chiasm/nerve
  • Late toxicity was assessed via CTCAE v. 4.0.

Results

  • Mean f/up time: 62.0 months; all patients were followed for over 6 months.
  • 6 patients (15.4%) with local failure (LF) and 6 deaths during follow-up (4 deaths due to tumor progression, 1 due to vascular complications, 1 due to pneumonia).
  • 5-year actuarial local control (LC) for all patients: 84%
  • 5 year actuarial overall survival (OS) for all patients: 81.8%
    • 5 year LC and OS for benign histology: 100%
    • 5 year LC and OS for atypical/anaplastic histology: 60% and 70% respectively
  • Grade 1-2 acute toxicity including skin erythema (n=25) and alopecia (n=24) was seen.
  • Grade 1-2 late toxicity seen in 11 patients
    • Pituitary dysfunction, brain edema, retinitis, optic neuropathies, ischemic stroke
  • 5 year grade >3 late toxicity-free survival rates were 84.5%
    • Grade >3 late toxicity seen in 5 patients (3 patients with brain necrosis/edema interfering with ADLs and 2 patients with grade 4 optic neuropathy causing unilateral blindness)
      • All of these patients had large volumes irradiated.
  • Univariate analysis:
    • LC negatively influenced by WHO grade (p=0.001), GTV (p=0.013) and male gender (p=0.058).
      • GTV size was also correlated with decreased LC. Local recurrence occurred in 1 patient with small volume treated (<24.1 cc) vs. 5 patients with large volume treated (>24.1 cc).

Author’s Conclusions

  • The authors conclude that proton therapy was able to effectively control complex benign meningiomas, except for patients with larger tumors or optic apparatus involvement.
  • They state that LC and OS rates seen in this study are comparable to previous work in this area from Uppsala, MGH, and Orsay studies.
  • Only a minority of patients presented with late I-II grade toxicities after proton therapy.
  • However, local control rates for atypical and anaplastic meningiomas continue to remain disappointing at current dose levels.
  • Dose escalation studies should be considered as a future work in this area.

Clinical Implications

  • Although the majority of meningiomas are benign tumors, they have the propensity to recur locally and can cause neurologic and ophthalmic consequences given their location.
  • Radiation in an effective treatment for control of complex benign and high grade meningiomas, however side effects of radiation such as brainstem necrosis or ophthalmic injury can be quite devastating, especially considering the high radiation doses required to control these tumors.
  • In the study presented here, these authors have examined proton therapy for treatment of meningiomas in an effort to minimize long-term toxicity while effectively controlling tumor.
  • The authors of this study were able to demonstrate that LC and OS were comparable to previous studies for small cohort of 39 patients.
  • However, local control rates for atypical/anaplastic meningiomas were not significantly improved using a proton therapy technique when compared to historical data. Results remain suboptimal.
  • Furthermore, severe toxicity, including brainstem necrosis and Grade 4 optic neuropathy, was seen in 15% of patients, all of whom had a large volume treated. Although these patients may have had tumors close to these critical structures, one needs to be extremely careful when treating these patients with proton therapy. Proton therapy, due to its high conformality index and range uncertainty, can deliver very high doses to adjacent structures, and may not be the optimal modality of treatment for certain meningiomas depending on location.
  • Limitations of this study include its small cohort and short-term follow up. To fully evaluate long-term toxicity outcomes in this population, many more years of follow-up data will be necessary.
  • Proton therapy offers an effective option for clinicians presented with the challenge of treating complex meningiomas, however they must proceed with caution in patients who are treated to large volumes and for tumors close to the brainstem or optic pathways. A comparison of various photon, SRS, and protons plans may be beneficial in these instances.


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