MALIGNANT NEOPLASM OF BRAIN-TARGET VOLUME DELINEATION

Initial assessment and workup

• In the management of patients with malignant primary brain tumors, obtain a detailed history and neurologic-focused physical examination.
• Perform appropriate laboratory investigations, including assessment of hormonal function as well as baseline blood counts for patients undergoing chemotherapy.
• Baseline visual field and visual acuity testing, audiometric assessment, and baseline neurocognitive function are all important.
• Baseline assessments allow comparison during and after treatment and help to identify treatment-related toxicities early.

Role of surgery and radiotherapy

• Maximal safe surgical resection, with an objective of achieving a gross-total resection, remains the standard of care for patients who are medically operable and have surgically accessible tumors.
• Definitive radiation therapy is used for patients who undergo a biopsy alone and adjuvant radiotherapy is used for the majority of patients after resection.
• The radiation therapy approach to benign variants of these tumors is discussed separately; this section focuses on malignant primary brain tumors.

Radiation techniques

• A variety of radiotherapy techniques are used in patients with malignant primary brain tumors, including:
  • 3D-conformal radiotherapy (3D-CRT)
  • Fractionated stereotactic radiotherapy (FSRT)
  • Intensity-modulated radiation therapy (IMRT)
  • Volumetric-modulated arc therapy (VMAT)
  • Stereotactic radiosurgery (SRS)
  • Proton beam radiotherapy (PBT)
• The choice of technique depends on tumor size, location, proximity to organs-at-risk (OARs), prior treatments, and institutional expertise.

Imaging for target delineation

• Accurate delineation of the target volumes and the organs-at-risk is key to determining the best treatment option for each patient and to creating an optimal radiotherapy treatment plan.
• Treatment planning MR images should be obtained as close as possible to the time of CT simulation.
• Sequences that best allow visualization of the tumor include T1-post contrast and FLAIR images.
• Sequences helpful for normal anatomy include:
  • T1 images to delineate the hippocampus
  • 3D T2 or CISS sequences to delineate cranial nerves

Patient positioning

• Patients with malignant primary brain tumors are typically simulated in the supine position.
• Arms are positioned extending parallel to the body with shoulders in a natural and comfortable position.

Immobilization devices

• For patients undergoing CT simulation and treatment, an indexed 3-point thermoplastic mask is used for immobilization.
• A 5-point thermoplastic mask can be used for patients with base-of-skull tumors or tumors close to the optic apparatus where reinforced neck positioning with the extended mask is helpful.
• For patients undergoing MRI simulation and treatment, a clam shell mask is used.

Head and neck position

• The head and chin are placed in a neutral position unless specific instructions for base-of-skull positioning are required.
• Careful alignment of external landmarks and immobilization system indices must be documented for reproducibility.

CT simulation parameters

• Axial CT simulation images are obtained with:
  • 1 mm slice thickness for SRS, FSRT, or PBT
  • 2 mm slice thickness for 3D-CRT, IMRT, or VMAT
• The scan should include the entire head of the patient and extend down to the level of the shoulders.

MR imaging and image fusion

• Co-registration of diagnostic MR imaging is strongly recommended for target volume delineation for primary brain tumors, unless there is a clear medical or clinical contraindication.
• Intravenous contrast can be used to delineate primary tumors, resected tumor cavities, or to aid with fusion to pre-treatment MR imaging.

General principles

• Organs-at-risk (OARs) are delineated on the treatment planning CT scan with the aid of pre-treatment MR imaging.
• Planning risk volumes (PRVs) can be created for tumors abutting nearby critical organs to assist in dosimetric planning and dose assessment at the time of plan evaluation.
• A list of normal contours delineated for most primary brain tumors is summarized in Table 30.1 below.
• Examples of contours of key OARs for primary intracranial cases are provided in the “Benign Tumors of the CNS” chapter (Figs. 30.1–30.4).

Suggested organs-at-risk for primary brain tumors

Organ-at-risk
Brain
Uninvolved brain (brain—GTV or CTV, depending on clinical scenario)
Brainstem (brainstem core, brainstem surface)
Spinal cord
Right cochlea
Left cochlea
Right globe
Left globe
Right lens
Left lens
Right optic nerve
Left optic nerve
Optic chiasm
Right retina
Left retina
Right lacrimal gland
Left lacrimal gland
Right temporal lobe
Left temporal lobe
Right hippocampus
Left hippocampus
Hypothalamus
Pituitary

General treatment principles

• Patients with high-grade astrocytoma and oligodendroglioma undergo maximal safe resection for diagnosis and molecular characterization as well as to safely remove as much gross disease as feasible.
• Patients are treated with conventionally fractionated radiation therapy to a dose of 59.4–60 Gy along with chemotherapy, either in the concurrent or adjuvant setting.
• Poor-risk, elderly, or frail patients with high-grade gliomas can be treated with hypofractionated radiotherapy schedules, including:
  • 40.05 Gy in 15 fractions, or
  • 25 Gy in 5 fractions, with reduced margins (0.5–1 cm), with or without chemotherapy.

Recommended target volumes for high-grade glioma

Tumor type	Recommended dose / fractionation	GTV definition	Suggested CTV expansions	PTV expansions
Anaplastic glioma (enhancing tumor)	Sequential cone down: PTV1: 50.4 Gy at 1.8 Gy/fraction PTV2: 59.4 Gy at 1.8 Gy/fraction Simultaneous integrated boost: PTV1: 54.45 Gy at 1.65 Gy/fraction PTV2: 59.4 Gy at 1.8 Gy/fraction	GTV1 is defined by the T2 or FLAIR volume. GTV2 is defined by the post-operative cavity and residual tumor by the post-contrast T1 MRI.	CTV1 is defined by a 1.5 cm expansion, reduced around natural barriers to tumor spread. CTV2 is defined by a 1.0 cm expansion, reduced around natural barriers to tumor spread.	0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology.
Anaplastic glioma (non-enhancing tumor) IDH-wild type diffuse astrocytoma	PTV1: 59.4 Gy at 1.8 Gy/fraction	GTV is defined by the post-operative cavity volume and residual tumor by T2 or FLAIR.	CTV is defined by a 1.5 cm expansion, reduced around natural barriers to tumor spread.	0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology.
Glioblastoma	Sequential cone down: PTV1: 46 Gy at 2 Gy/fraction PTV2: 60 Gy at 2 Gy/fraction Simultaneous integrated boost: PTV1: 50–51 Gy at 1.67–1.7 Gy/fraction PTV2: 60 Gy at 2 Gy/fraction	GTV1 is defined by the T2 or FLAIR volume. GTV2 is defined by the post-operative cavity and residual tumor by the post-contrast T1 MRI.	CTV1 is defined by a 2 cm expansion, reduced around natural barriers to tumor spread. CTV2 is defined by a 2 cm expansion, reduced around natural barriers to tumor spread.	0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology.
Gliosarcoma	Sequential cone down: PTV1: 46 Gy at 2 Gy/fraction PTV2: 60 Gy at 2 Gy/fraction Simultaneous integrated boost: PTV1: 50–51 Gy at 1.67–1.7 Gy/fraction PTV2: 60 Gy at 2 Gy/fraction	GTV1 is defined by the T2 or FLAIR volume. GTV2 is defined by the post-operative cavity and residual tumor by the post-contrast T1 MRI.	CTV1 is defined by a 1.5–2 cm expansion, reduced around natural barriers to tumor spread. CTV2 is defined by a 1.5–2 cm expansion, reduced around natural barriers to tumor spread.	0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology.

Additional notes

• For hypofractionated schedules such as 25 Gy in 5 fractions, margins around the GTV are typically reduced to 0.5–1 cm.
• Treatment paradigms for patients with gliosarcoma mirror those for patients with glioblastoma.

Clinical background

• Meningiomas represent the most common primary intracranial tumors in adults.
• Fewer than 30% of meningiomas are classified as atypical (WHO grade II) or malignant (WHO grade III).
• Adjuvant radiation therapy can be considered for patients who undergo a gross-total resection of WHO grade II meningioma.
• Adjuvant radiation therapy is recommended for patients who undergo a subtotal resection of a WHO grade II meningioma.
• For patients with a WHO grade III meningioma, adjuvant radiation therapy is recommended for all patients regardless of the extent of resection.
• Given that grade II and III meningiomas can involve bone and brain, it is important on image review and target volume delineation to recognize that skull and normal brain are not necessarily natural barriers to tumor spread.
• Margins should include normal brain if there is brain invasion noted as part of operative or pathology findings.
• Adjuvant radiation therapy is recommended for patients who undergo resection of a hemangiopericytoma.

Recommended target volumes for grade II/III meningioma and hemangiopericytoma

Tumor type	Recommended dose / fractionation	GTV definition	Suggested CTV expansions	PTV expansions
Grade II meningioma (upfront)	PTV: 54–59.4 Gy at 1.8 Gy/fraction	GTV is defined by the post-operative cavity and residual tumor, including suspicious dural and/or bone involvement by the post-contrast T1 MRI.	CTV is defined by a 0.5 cm expansion, reduced around natural barriers to tumor spread.	0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology.
Grade II meningioma (recurrent)	PTV: 54–59.4 Gy at 1.8 Gy/fraction	GTV is defined by the post-operative cavity and residual tumor, including suspicious dural and/or bone involvement by the post-contrast T1 MRI. Evaluation of prior dural attachment at initial diagnosis is also recommended.	CTV is defined by a 0.5–1.0 cm expansion, reduced around natural barriers to tumor spread.	0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology.
Grade III meningioma (upfront or recurrent)	PTV: 59.4–60 Gy at 1.8–2 Gy/fraction	GTV is defined by the post-operative cavity and residual tumor, including suspicious dural and/or bone involvement by the post-contrast T1 MRI. Evaluation of prior dural attachment at initial diagnosis is also recommended.	CTV is defined by a 1–1.5 cm expansion, reduced around natural barriers to tumor spread.	0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology.
Hemangiopericytoma	PTV: 59.4–60 Gy at 1.8–2 Gy/fraction	GTV is defined by the post-operative cavity and residual tumor, including suspicious dural and/or bone involvement by the post-contrast T1 MRI.	CTV is defined by a 1.5 cm expansion, reduced around natural barriers to tumor spread, but should include the entirety of involved bone.	0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology.