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15 years of Proton Radiosurgery Experience at the Ithemba Labs, Long Term Results for AVM’s, Meningiomas, and Acoustic Neuromas

Reviewer: Eric Shinohara MD, MSCI
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 26 de mayo del 2008

Presenter: Frederick Vernimmen
Presenter's Affiliation: Stellenbosch University
Type of Session: Scientific

Background

• There are a number of benign diseases which can be treated with radiation and the present study is a review of the long term outcomes in patients treated with protons for AVM, meningiomas and acoustic neuromas at Ithemba labs.

• Acoustic Neuromas (AN) arise from schwann cells which surround the vestibular portion of the vestibulocochlear nerve. AN comprise approximately 8% of adult brain tumors and occur at a median age of 50 years. Approximately 10% of patients who develop AN have neurofibromatosis type 2. The majority of patients will present with tinnitus or hearing loss and slightly more than half will have unsteadiness or vertigo.

• Prior studies have shown that stereotactic radiation is effective (97% recurrence free survival at 10 years) and has good preservation of function (70% of patients with unchanged hearing, 79% with facial nerve preservation, 73% with trigeminal nerve preservation).

• AVM’s occur in about 0.1% of the population. 90% of AVM’s are supratentorial and most of the remaining AVM’s are located in the posterior fossa. They account for approximately 1-2% of all strokes. Stereotactic radiation can be used to treat AVM with success largely dependent on the size of the AVM. An 80% ablation rate is seen in AVM of less than 3 cm with AVM’s larger than 3 cm responding 30-70% of the time. Higher doses appear to be more effective.

• Meningiomas arise form the arachnoid cap cells of the meningies and 90% are benign. They account for approximately 13-30% of all primary intracranial tumors. Radiation therapy is commonly used for incompletely resected tumors and as a primary treatment. Prior studies have shown that radiation decreases recurrence rates in patients who are incompletely resected (~50%) and prolongs the time to recurrence. The best candidates for stereotactic radiation have meningiomas measuring approximately 3 cm in size. Patients seem to have comparable rates of control with surgery versus stereotactic radiation, however 5-10% of patients will develop complications related to radiation.

Materials and Methods

This is a retrospective single institution review of long term control in AVM, meningiomas and acoustic neuromas treated with fractionated stereotactic proton therapy. A total of 500 patients have been treated at Ithemba labs since 1993 and of these 500 patients, 81 were treated for AVM, 41 for meningioma, and 64 for acoustic neuroma. The majority of the 500 patients were treated with radiosurgery as the beam was available only two days a week. Only small fields were available due to limitation related to the passive scatter beam that was used.

All patients were treated with 3-4 fields with two to three fractions. Fractions were given twice a week (Monday and Friday) and all fields were treated daily. A fixed 200 MeV passive scatter photon beam was used for treatment and custom collimation was used for each patient. Each patient was treated using a non-invasive stereophotogrammatic patient support and positioning system. A mask and bite block was used for immobilization. Markers on the mask were monitored using a video camera system and aligned using a computerized adjustable chair. Treatment planning was done using Voxelplan with the addition of Proxelplan for the Bragg peak dose calculation model. No distal beam shaping was used.

Results

AVM:

• Median Age: 34 years
• Male/Female Ratio: 1.8
• Median ICRU reference dose: 20.1 CGE
• Median volume: 15.6 cc (range: 1.7 to 110.6 cc)
• Median Follow Up: 4.8 years
• Overall Obliteration: 52% and this was volume dependent (<14 cc 75% and for patients with AVM >14 cc 46%)
• Clinical Outcome: 53% of patients had a good response and 34% of patients had stable disease The AVM’s in this study tended to be larger than in prior studies. When examining results comparing AVM measuring 20-30 cc treated in the present study with prior studies of similar sized AVM treated with stereotactic radiosurgery results were comparable per the authors.
• Meningioma:
• Median Age: 53 years
• Male/Female Ratio: 3
• Median ICRU reference dose: 21.5 CGE
• Median volume: 8.4 cc (range: 2.6 to 63 cc)
• Median Follow Up: 6.8 years
• Radiologic Control: (defined as the absence of growth) 89%
• Clinical Improvement: 60% It was noted by the authors that there were a significant number of patients who did not have a radiological response but who did have a clinical response. As with AVM, these meningiomas tended to be larger compared with prior radiosurgery studies but the results were comparable to prior radiosurgery studies per the authors.
• Acoustic Neuromas:
• Median Age: 42 years
• Median ICRU reference dose: 16.3 CGE
• Median volume: 7 cc (range: 1 to 45.7 cc)
• Median Follow Up: 5.3 years
• Radiologic Control: (defined as the absence of growth) 95%
• Hearing/Facial Nerve Preservation: 61%/87% It was noted by the authors that half of patients had hearing loss prior to treatment. They noted that the median dose in the present study was higher than prior radiosurgery studies (generally 12-13 Gy). The authors note that results from this study were consistent with prior radiosurgery studies examining treatment of acoustic neuromas. They did note that protons were particularly useful in the treatment of bilateral acoustic neuromas.

Author's Conclusions

1. This is a retrospective single institution study
2. Results are comparable with photon based radiosurgery
3. The lesions in the present study tended to be larger than prior studies
4. It appeared that there was an advantage to stereotactic proton therapy in the treatment of bilateral acoustic neuromas
5. There have been no cases of secondary malignancy thus far

Clinical/Scientific Implications

Current radiotherapy techniques with gamma knife and linac based stereotactic radiotherapy have been fairly effective in the treatment of the above mentioned benign conditions. How then do protons potentially improve on what can be achieved with photon based radiosurgery? There is the potential for better conformality with proton beam therapy due to the ability to control the distal boarder of the treatment field. Spot scanning beam proton therapy may allow even greater control of the dose distribution and spare even more normal tissue, which due to the location of these masses is critical. Specifically, in acoustic neuromas hearing preservation as well as sparing of the facial nerve is important and it may be possible to improve on the rates of nerve damage with proton therapy, perhaps best with fractionated therapy rather than radiosurgery. The present study appears to show a high rate of preservation of the facial nerve and hearing despite the higher dose used in the present study. The AVM, acoustic neuromas and meningiomas tended to be larger in this study and it is possible that proton based radiosurgery may be able to address larger tumors than can be treated with gammaknife safely. However, the proton range is not absolute and there is some uncertainty about where the distal boarder ends. Hence, until we are better able to account for this it critical to consider this uncertainty during treatment planning.

Whenever treating benign disease with radiation it is always important to consider serious side effects as these diseases can often be treated with other modalities and are usually not fatal. Secondary malignancy is one of the most serious potential late effects and unfortunately more follow up is needed for all three groups. In theory, there should be less dose delivered to normal tissues with proton therapy reducing the risk for secondary malignancy. Retrospective data from Harvard suggest that secondary malignancy is uncommon with proton treatment, despite concerns about neutron contamination. Hence, secondary malignancy may not be a large problem in the long term follow up of these patients.

For proton therapy to become a standard indication for treatment of these lesions, clinical trials showing superiority over conventional stereotactic and gamma knife are needed due to the cost of this therapy over the other modalities. This is particularly important in a disease where currently available treatments are tolerated well and successful.