RTOG 0539 - "Phase II Trial of Observation for Low-Risk Meningiomas and of Radiotherapy for Intermediate- and High-Risk Meningiomas"

Treatment Plan    (Supplied Drug:  N/A)

STEP 1 REGISTRATION

Central Path Review / Histology Confirmation

Must be completed b/f STEP 2 registration can occur.

STEP 2 REGISTRATION

Group I (Low Risk)

Observation

Group II (Intermediate Risk)

RT:  54Gy in 30 fx (3D-CRT or IMRT)

Group III (High Risk)

RT:  60Gy in 30 fx (must be IMRT)

Eligibility

• Histol-documented WHO grade I, II, or III meningioma, new dx or recur, of any resection extent confirmed by central path review.  Extent of resection is based on neurosurgeon's asmt & post-op MRI.

  • Group I (low-risk):  New dx WHO grade I meningioma that is gross totally resected (Simpson's grade I, II, or III resections w/no residual nodular enhancement on post-op imaging) or subtotally resected (residual nodular enhancement or Simpson grade IV or V excision).

  • Group II (intermediate-risk):  New dx gross totally resected WHO grade II meningioma or recur WHO grade I meningioma irrespective of resection extent.

  • Group III (high-risk):  New dx or recur WHO grade III meningioma of any resection extent; pts w/recur WHO grade II meningioma of any resection extent; or new dx subtotally resected WHO grade II meningioma.  For new dx meningioma,  the histologic dx must have been reached w/i 6 mos of Step 2 regist.

  • For new dx meningioma, the histol dx must be made w/i 24 wks prior to Step 2 regist.  For recur meningioma, there are no time constraints.  Additional resection or bx is encouraged for pts w/recur, but is not required.  If further bx or resection is performed at recurrence, these specimens must be submitted (submission of orig path specimens is encouraged, but not required).  Dx of recur solely on basis of imaging is permitted, but if no additional resection is performed, specimens from prior resection must be submitted.

  • For new dx or surgically treated recur meningioma, the operating neurosurgeon must provide Simpson grade for degree of resection.

• Zubrod 0-1.

• Age >18.

• MRI w/i 12 wks prior to Step 2 regist.  Both pre-op & post-op MRIs are required for all new dx Group I, II, or III pts.  For Group II or III pts w/recur or progres meningioma & w/o recent surgery, a pre-op study may not apply, but MRI documentation of recur or progres is required.  MRIs must include pre-contrast T1, T2, flair images, & post-contrast multiplanar T1.  Post-op MRI w/i 12 wks of surgery.

  • Group I:  All pts will have surgery.  Pre- & post-op MRIs are required.

  • Group II:  Surgery will be done for those w/gross totally resected WHO grade II meningioma.  Pre- & post-op MRIs are needed.  For those w/recur WHO grade I meningioma, pre- & post-op MRIs are required if surgery is done for recur/progres tumor.  Only follow-up imaging documenting recur/progres will apply if further surgery is not completed.

  • Group III:  Surgery will be done for those w/new dx WHO grade III meningioma.  Pre- & post-op MRIs are required.  For those w/recur WHO grade II or III meningioma, pre- & post-op MRIs are required if surgery is done for recur/progres tumor.  Only follow-up imaging documenting recur/progres will apply if further surgery is not completed.

• Women of childbearing potential who are intermediate- or high-risk:  1) negative serum pregnancy test w/i 14 days prior to Step 2 regist; & 2) must practice adequate contraception from time of negative serum pregnancy test through entire course of EBRT.

• No extracranial meningioma.

• No multiple meningiomas.

• No hemangiopericytoma.

• No major medical illness or psychiatric impairment to preclude informed consent or protocol therapy (investigator's opinion).

• No prior RT to scalp, cranium, brain, or skull base.

• No prior invasive malignancy (except non-melanoma skin cancer) unless disease-free >3 yrs.

• No severe, active co-morbidity (not limited to):

  • Unstable angina &/or CHF requiring hospitalization at time of Step 2 regist

  • Transmural MI w/i last 6 mos

  • Acute bacterial or fungal infection requiring IV antibiotics at time of Step 2 regist

  • COPD exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at time of Step 2 regist

  • Hepatic insufficiency resulting in clinical jaundice &/or coagulation defects.  NOTE:  Lab tests for liver function & coagulation parameters are not required for study entry.

  • AIDS based on current CDC definition.  NOTE:  HIV testing is not required for study entry.

  • Active connective tissue disorders if pt is intermediate- or high-risk.

• PRE-STUDY REQUIREMENTS:

  • Neuro exam, H&P*

  • MMSE**

  • Steroid dose documentation*

  • Documentation of other hormonal agents*

  • Perf status*

  • CBC/diff/platelets, ANC*

  • Brain MRI***

  • Serum pregnancy test (if applicable, Groups II & III)**

  • Tissue block (central path review) - MANDATORY prior to Step 2 regist##

  • Tissue block or fresh frozen tissue***#

  • Serum or plasma***#

  • Buffy coat***#

  • Urine***#

  *       Within 8 wks prior to Step 2 regist

  **     Within 14 days prior to Step 2 regist

  ***   Within 12 wks prior to Step 2 regist

  #       Encouraged, but not mandatory.  Pts must be offered opportunity to participate.  Contact KCCOP for kit.  Ship via overnight delivery (send Mon-Wed only for frozen specimens; can be stored at -80^oC until ready for shipment).  See protocol for collection & shipping requirements.

  ##    1) 1 H&E stained slide per paraffin block; 2) paraffin-embedded tissue tumor block or 2mm diameter core of tissue punched from block containing the tumor; & 3) path report documenting that materials submitted meet protocol constraints.

• Signed informed consent.