Indications for Radiotherapy

Surgical resection is the mainstay of treatment of meningiomas, but there are a variety of cases for which surgery alone may not be adequate treatment:

• 
  

  Meningiomas not amenable to curative resection

  
  
• 
  

  Recurrent or multiply recurrent meningiomas after surgery, which are at high risk for further recurrence at shorter intervals1

  
  
• 
  

  Malignant meningiomas, and perhaps also atypical meningiomas, which have a high risk of recurrence even after total resection2–5

Furthermore, subtotal resection with later postoperative radiotherapy may be preferable over complete resection in some cases:

• 
  

  Meningiomas for which risks of complete resection outweigh benefits (e.g., optic nerve sheath meningiomas and many cavernous sinus meningiomas)

There are also instances in which surgery may not even be indicated for tumors with typical appearance of benign meningioma:

• 
  

  In patients who are not surgical candidates due to medical inoperability or advanced age

  
  
• 
  

  In patients with asymptomatic or minimally symptomatic tumor in whom surgical debulking is not necessary for symptom relief and in whom curative surgical resection would not be possible or in whom risks of surgery may outweigh benefits.

In such cases, radiosurgery or radiation therapy may be indicated, either as an alternative to surgical resection, postoperatively, or at the time of progression or recurrence after surgery.

As shown in Table 40.1 , gross total (Simpson grade I, II, or III)6 resection alone results in a high likelihood of durable tumor control, 96% as a crude percentage7 with actuarial freedom from progression probabilities of up to 98% at 5 years4 and 75 to 80% at 10 years.1,3,5 However, subtotal (Simpson grade IV) resection alone yields crude tumor freedom-from-progression rates of only 40 to 52%7,8 and freedom-from-progression or progression-free survival probabilities of only 38 to 62% at 5 to 10 years.1,3–5,9,10 The addition of postoperative radiotherapy to subtotal resection increases the progression-free survival probability to 78 to 91% at 5 to 10 years, comparable to the results of gross total resection alone.3,9,10

As clinicians have become more comfortable with radiotherapy in the treatment of meningiomas, it has become more commonplace to manage selected patients with radiotherapy alone as an alternative to surgery alone or surgery with postoperative radiotherapy, with equivalent results.11–15 Thus radiotherapy alone without surgical resection yields progression-free survival equivalent to that of subtotal resection plus radiotherapy.

The choice of radiosurgery versus radiotherapy is governed primarily by risk to surrounding normal tissues. The tumor dose used for radiosurgery exceeds normal tissue tolerance but is acceptable for small targets because of the very precise targeting and very steep dose fall-off outside of the target. The larger the target, the less steep the dose fall-off and the greater the volume of the shell of surrounding normal tissue exposed to a potentially damaging radiation dose level. Thus radiosurgery may be an excellent treatment option for small tumors less than ~3 to 4 cm in diameter and at least 2 to 3 mm away from the optic nerve and chiasm. For larger tumors or those adjacent to or compressing optic nerve or chiasm or with extensive brain stem compression, radiotherapy given over 5 to 6 weeks is preferred and is generally well tolerated by adjacent normal tissue.

Limitations and Expectations of Radiotherapy

Although radiotherapy is generally successful at preventing further growth of benign meningiomas, it tends to result in little or no tumor shrinkage over time owing to underlying radiobiological principles. The major mode of cell death after exposure to ionizing radiation is via double-strand breaks in DNA, and for most kinds of tumor cells, cell death occurs after one or more cell divisions, because DNA mistakes accumulate in daughter cells. Rapidly dividing cells tend to die quickly after radiotherapy, resulting in marked tumor shrinkage or even complete disappearance of malignant tumors over weeks or months. In contrast, very slowly dividing cells may survive for many years after radiotherapy, resulting in little or no tumor shrinkage. Thus bulky benign tumors causing significant symptoms from mass effect may require surgical debulking, given that radiation therapy cannot be counted upon to reduce significant tumor mass effect in a timely manner. Over years after radiotherapy, ~20 to 30% of meningiomas shrink at least 2 mm in diameter or 25% by volume ( Table 40.2 ). In one series, 14% of meningiomas had partial response (at least 50% shrinkage) after radiotherapy,16 but complete disappearance is rare. Cases of rapid, marked tumor shrinkage in the absence of histological verification should raise one’s suspicion of a diagnosis of dural metastasis, hemangiopericytoma, or leiomyosarcoma, which typically shrink dramatically after radiosurgery or radiotherapy.

On the other hand, visible tumor shrinkage is not necessary to see improvement in cranial nerve deficits; symptomatic improvement of cranial nerve deficits is relatively common after radiotherapy, despite the fact that there may be little or no visible tumor shrinkage. Papers containing detailed reports of symptomatology before and after radiotherapy describe improvement in 50 to 81% of symptoms, including cranial neuropathies,12,17 and clinical improvement in 43 to 71% of patients ( Table 40.2 ).11,14,18,19 This is particularly relevant for cavernous sinus meningiomas and optic nerve sheath meningiomas. In the case of optic nerve sheath meningiomas, surgery often carries a high risk of visual deterioration, whereas primary radiotherapy has a low risk of visual deterioration and may improve vision in about one third to one half of the patients with useful vision before radiotherapy.20,21

Evaluation of the success of radiotherapy for meningiomas is complicated by the facts that untreated meningiomas may grow very slowly and treated meningiomas may shrink very slowly, if at all. Because meningiomas are expected to remain stable or shrink very slowly over time, results of radiotherapy for meningiomas are usually described in terms of freedom from tumor progression or progression-free survival (sometimes called relapse-free survival), and at least 5 to 10 years of follow-up are desirable to assess treatment results.

Another important major limitation of radiotherapy is that it can generally only be given once to the same area without incurring major risks of brain necrosis or other serious complications, unless the volume of normal tissue exposed to retreatment is very small. The radiation dose that is required for good tumor control is close to the tolerance of normal brain tissue, and normal cells repair radiation injury to some extent, but never completely.