Whole Brain — Hippocampal Avoidance

CNSBrainWhole brainHA-WBRTHippocampal avoidanceBrain metastasesIMRTVMATNRGPlan Evaluation
Overview

Hippocampal-avoidance whole-brain radiotherapy: IMRT or VMAT that treats the whole brain to 30 Gy in 10 fractions while holding the hippocampi to a low dose. The planning problems are an MRI-defined avoidance structure in the middle of the target, a steep dose gradient around it, and a clear priority order between the optic structures, the hippocampi and target coverage.

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Schedule & Planning Goals

Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) treats the whole brain to 30 Gy in 10 fractions while keeping the hippocampi to a low dose. It is a different planning technique from conventional whole brain: inverse-planned IMRT or VMAT instead of two lateral fields, and an MRI-defined avoidance structure in the middle of the target.

It is based on RTOG 0933 and the randomized NRG CC001 trial, where HA-WBRT with memantine reduced cognitive decline compared with conventional whole brain with memantine. The ASTRO guideline recommends it for patients with a good prognosis and no metastases in or near the hippocampi who are receiving whole-brain treatment.

In the CC001 protocol, plans were normalized so that 95% of the PTV received 30 Gy, and the PTV was also scored on its hottest 2% (D2% ≤37.5 Gy per protocol) and on D98% (≥25 Gy per protocol). The protocol ranked the planning priorities in this order:

  1. Optic chiasm
  2. Optic nerves
  3. Hippocampi
  4. PTV
  5. Lenses

CC001 did not use a boost to individual metastases, although some centers add a simultaneous integrated boost.

Simulation & Imaging

Hippocampal avoidance depends on MRI far more than conventional whole brain does.

Mask and head position
Hippocampal avoidance relies on a steep dose gradient, so the head must be in the same position every day.

What is it?

Supine in a thermoplastic mask with a neck support, as for other brain treatment.

Why does it matter?

The hippocampi sit in the middle of a 30 Gy target with a steep dose gradient around them, so the head has to be in the same position every day for the avoidance to work.

Planning CT
Thin slices keep the small hippocampal contours and the dose gradient around them accurate.

What is it?

A thin-slice CT of the whole head. CC001 asked for slices no thicker than 2.5 mm, matched to the MRI slice thickness as closely as possible. More →

Why does it matter?

Thin slices keep the small hippocampal contours and the steep dose gradient around them accurate.

Image fusion — MRI
The hippocampi are contoured on a thin-slice MRI, so the fusion around the temporal lobes has to be right.

What is it?

Image fusion aligns an outside scan with the planning CT so the target can be drawn using information the CT doesn't show. For hippocampal avoidance this is a thin-slice, contrast-enhanced 3D T1-weighted MRI (such as SPGR or MP-RAGE) plus T2 FLAIR. The MRI doesn't need to be taken in the treatment position, but geometric distortion has to be corrected.

Why does it matter?

The hippocampus can't be contoured reliably on CT. The MRI also confirms that there are no metastases in or next to the hippocampi. A poor fusion misplaces the avoidance structure, so the registration is checked around the temporal lobes. Because the eyes move between scans, CC001 contoured the lenses and optic nerves on the CT.

Target & Avoidance Structures

What each structure represents. Structure definitions come from your protocol.

CTV — Whole brain

Definition

The whole-brain parenchyma. CC001 took it down to the foramen magnum; one current protocol extends it to C1, or to C2 when there are posterior fossa metastases.

Why it matters

Unlike the conventional technique, the target is a contoured volume rather than a field edge on a DRR, so the lower border and the tissue near the skull base are defined by the contour.

Contouring resources

Organ contouring guides →

Relevant protocols

Hippocampi — The organ being spared

Definition

Both hippocampi, contoured on the fused MRI by the treating physician using the RTOG hippocampal contouring atlas, with each side also named separately.

Why it matters

The dose limits apply to these contours, so their accuracy decides whether the plan truly spares the hippocampi. Trials required contouring credentialing.

Contouring resources

Organ contouring guides →

Relevant protocols

Hippocampal avoidance region — Removed from the PTV

Definition

The hippocampi grown in three dimensions — by 5 mm in CC001 — to form a region that is subtracted from the target.

Why it matters

It gives the dose room to fall from 30 Gy to the hippocampal limit. Tissue inside the region but outside the hippocampi receives an intermediate dose.

Contouring resources

Organ contouring guides →

Relevant protocols

PTV — Planning target volume

Definition

The CTV minus the hippocampal avoidance region. CC001 added no setup margin; one current protocol adds a small margin before removing the avoidance region.

Why it matters

Because the PTV has a hole in its center, some hot spots near the avoidance region are expected; the protocol's D2% limit caps them.

Contouring resources

Organ contouring guides →

Relevant protocols

Organs at Risk & Dose Constraints

Click an organ for its anatomy, why it matters and contouring resources. Superscripts link to the source of each value.

Organ30 Gy / 10 fxNRG CC001
HippocampusBoth hippocampi, evaluated as one structure. The limits apply to the hippocampi, not to the avoidance region around them.
  • D100% ≤9 Gy (per protocol), ≤10 Gy (variation acceptable)1
  • Max (0.03 cc) ≤16 Gy (per protocol), ≤17 Gy (variation acceptable)1
Optic Chiasm & Optic NervesChiasm and each optic nerve. Top of the planning priority list.
  • Max (0.03 cc) ≤30 Gy (per protocol), ≤37.5 Gy (variation acceptable)1
LensTarget coverage should not be compromised to meet this.
  • Max ≤5 Gy (ideal)2
  • Above the variation-acceptable level, the protocol scores a plan as an unacceptable deviation.
  • RTOG 0933 and one current protocol use ≤37.5 Gy as the optic limit.
References (2)
  1. NRG CC001 — NRG-CC001 protocol — A Randomized Phase III Trial of Memantine and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Patients With Brain Metastases. Protocol document, NRG-CC001 (ClinicalTrials.gov NCT02360215) Source
  2. eviQ 3882 — Brain metastases palliative EBRT hippocampal avoidance whole brain (eviQ ID 3882). eviQ Radiation Oncology protocol 3882 Source

Values quoted from NRG CC001 and eviQ 3882 (last reviewed 21 August 2025; review due 31 December 2029), checked by DoseLab on 2026-09-25. Verify against your protocol, institutional policy and physician directive before clinical use.

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Protocols & Literature

Clinical protocolSource Verified

The NRG CC001 trial protocol (version date 26 September 2017, copy posted on ClinicalTrials.gov for NCT02360215). Arm 1 was standard whole-brain radiotherapy with 3D conformal fields; arm 2 was IMRT-based hippocampal avoidance, both 30 Gy in 10 fractions with memantine. Sections 5.2.4–5.2.8 define the CTV and PTV, the required structures (hippocampi, the hippocampal avoidance region, lenses, optic nerves and chiasm), the normalization, the per-protocol and variation-acceptable limits for the PTV, hippocampi and optic structures, and the planning priority order. DoseLab's hippocampal avoidance table quotes section 5.2.7 directly.

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Landmark trialUnder Review

Phase 3 trial of 518 patients with brain metastases randomized to whole-brain radiotherapy with or without hippocampal avoidance, both with memantine. Hippocampal avoidance lowered the risk of cognitive failure with no difference in survival or intracranial control. Citation checked against Crossref.

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Landmark trialUnder Review

Final results of NRG CC001 with more than a year of median follow-up: sustained preservation of cognition and fewer patient-reported neurologic symptoms with hippocampal avoidance. Citation checked against Crossref.

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Landmark trialUnder Review

Single-arm phase 2 trial of hippocampal-avoidance whole-brain radiotherapy, 30 Gy in 10 fractions, compared with a historical control; it showed less memory decline at 4 months. Its protocol defined the hippocampal contouring and dose limits later used in NRG CC001. Citation checked against Crossref.

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