Hippocampal-Avoiding Whole Brain Irradiation With Simultaneous Integrated Boost for Treatment of Brain Metastases

We propose to use conformal avoidance of the hippocampal region during whole brain
radiotherapy to reduce the dose to the hippocampi, thereby putatively limiting the
radiation-induced inflammation of the hippocampal region and subsequent alteration of the
microenvironment of the neural progenitor cells

Inclusion Criteria:

1. Pathologically (histologically or cytologically) proven diagnosis of a
non-hematopoietic malignancy other than small cell lung cancer and germ cell
malignancy.. Direct biopsy of CNS lesions is not necessarily required although could
constitute an allowed site of tissue confirmation as medically prudent. Patients who
have been disease free for more than 5 years prior to the appearance of CNS metastases
should undergo repeat biopsy of either a systemic metastasis or the CNS metastases to
confirm the recurrent malignancy.

2. Patients with measurable brain metastasis outside a 5-mm margin around either
hippocampus

3. Patients with measurable brain metastasis who have not been or will not be treated
with SRS or surgical resection (Note: These treatment options are only permitted at
relapse)

4. History/physical examination within 28 days prior to registration

5. Patients must fall into RTOG recursive partitioning analysis (RPA) class I or II

6. Patients must have a life expectancy of at least 4 months.

7. Age ≥ 18 years

8. Karnofsky performance status ≥ 70

9. Patients must provide study-specific informed consent prior to study entry

10. Women of childbearing potential and male participants must practice adequate
contraception

11. Women of childbearing potential must have a negative, qualitative serum pregnancy test
≤2 weeks prior to study entry

Exclusion Criteria:

1. Patients with greater than 9 discrete metastases on MRI.

2. Patients with leptomeningeal metastases

3. Patients with measurable brain metastasis not resulting from small cell lung cancer
and germ cell malignancy

4. Plan for chemotherapy or targeted therapies during WBRT or over the subsequent 7 days

5. Contraindication to MR imaging such as implanted metal devices or foreign bodies,
severe claustrophobia AND patients unable to receive gadolinium contrast agents

6. Serum creatinine > 1.4 mg/dl ≤ 28 days prior to study entry

7. Prior radiation therapy to the brain

8. Patients planning to undergo radiosurgery to any CNS lesion OR patients planning to
have surgical resection of ALL of their CNS lesions