40 Conformal Radiation Techniques for Meningiomas



10.1055/b-0034-81219

40 Conformal Radiation Techniques for Meningiomas

Sneed Penny K., Barani Igor J.

Radiation therapy plays an important role in the management of meningiomas that are not amenable to complete surgical resection or radiosurgery. In general, radiation therapy given 5 days weekly over ~6 weeks yields a high probability of preventing further tumor growth with a relatively low risk of significant complications. This chapter discusses the indications for conformal radiotherapy, limitations and expectations, techniques, results, and complications.



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 resection25


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.1,35,9,10 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.1115 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.




































































































Table 40.1 Results of Surgery ± Radiotherapy for Meningiomas

First Author


Year


n


Median or Mean Follow-Up (years)


Freedom from Progression or Progression-Free Survival Probability (No. of Patients)


Time Point


GTR Alone


STR Alone


Radiotherapy ± STR


Mirimanoff1


1985


225


~6


80% (145)


45% (80)


NA


10 years


Barbaro7


1987


135


6.5


96% (51)


40% (30)


68% (54)


Crude


Miralbell9


1992


115


6.0



48% (79)


78–88% (36)


8 years


Mahmood4


1994


246


5.2


98% (181)


62% (65)



5 years


Peele8


1996


86


~4



52% (44)


100% (42)


Crude


Condra3


1997


246


8.2


80% (174)


40% (55)


87% (17)


10 years


Stafford5


1998


581


9


75% (463)


39% (115)



10 years


Soyuer10


2004


92


7.7


77% (48)


38% (32)


91% (12)


5 years


Abbreviations: GTR, gross total (Simpson grade I–III) resection; STR, subtotal (Simpson grade IV–V) resection.



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.







































































































































































































































































Table 40.2 Results of Radiotherapy for Meningiomas, With or Without Prior Subtotal Resection

First Author


Year


Total No. of Patients


Benign/Atypical/Malignant/No Tissue


Radiation Technique


Median or Mean Dose (Gy)


Median or Mean Follow-Up (years)


FFP/PFS Probability %


Time-Point (years)


Incidence of


Clinical Improvement %


Tumor Shrinkage %


Grade 3–5 Late Toxicity %


Goldsmith22


1994


117


117/0/0/0


EBRT


54.0


3.3


77


10




3.6


Nutting25


1999


82


82/0/0/0


EBRT


55–60


9


–/83


10




13


Vendrely15


1999


156


65/5/5/81


EBRT


50


3.3


79*/89.5


5


59


29


8


Wenkel30


2000


46


46/0/0/0


Protons+RT


59.0


4.4


–/88


10




20


Pourel26


2001


45


26/2/5/12


EBRT


56


2.5


–/76


5




2.2


Dufour18


2001


31


20/0/0/11


EBRT


52


6.1


–/93


10


59§/71


29


3.2


Jalali23


2002


41


33/0/0/8


FSRT


55


1.8


100/91


3


27


22


12.2


Uy28


2002


40


25/0/0/15


IMRT


50.4


2.5


93/88


5



23


5


Pirzkall19


2003


20


16/0/0/4


IMRT


52


3


100/100



60


25


0


Selch27


2004


45


29/0/0/16


FSRT


50.4


3


97/97


3


20


18


0


Weber29


2004


16


11/2/0/3


Protons


56


2.8


92/92


3


13


19


12.5


Milker-Zabel14


2005


317


153/26/0/138


FSRT


57.6


5.7


–/89


10


43


23


0


Noël17


2005


51


44/0/0/7


Protons+RT


60.6


2.1


98/98


4


69§


20


3.9


Henzel11


2006


224


113/10/6/95


mostly FSRT


55.8


3


97/–


5


43


46


0


Milker-Zabel24


2007


94


51/9/4/30


IMRT


57.6


4.4


94*/95


5


40


20


4


Liter12


2009


100


26/0/0/74


FSRT


45


2.8


94/–


5


50–81§


9


0


Metellus13


2010


53


22/3/0/28


FSRT


52.9


6.9


–/96


10


58


30


1.9


Abbreviations: EBRT, external beam radiotherapy; FFP, freedom from progression; FSRT, fractionated stereotactic radiotherapy; IMRT, intensity-modulated radiotherapy; PFS, progression-free survival; RT, radiotherapy.


* Crude percentage rather than actuarial probability.


† Excluding atypical or malignant meningiomas.


§ Percentage of patients with improvement, by symptom.

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Jul 14, 2020 | Posted by in NEUROLOGY | Comments Off on 40 Conformal Radiation Techniques for Meningiomas
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