Trastuzumab emtansine and stereotactic radiosurgery: an unexpected increase in clinically significant brain edema.
BACKGROUND
In the last 10 years, multiple new targeted agents have been developed for patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. Up to 55% of patients with HER2+ breast cancer will develop brain metastases requiring some form of radiation therapy. The interaction between radiation and these targeted agents is unknown and previously unreported.


METHODS
In this series, we describe 4 patients who developed clinically significant brain edema at sites of treated brain metastases. These patients were treated with stereotactic radiosurgery and trastuzumab emtansine, the newest FDA-approved agent for metastatic HER2+ breast cancer. Additionally, we present rates of clinically significant radiation necrosis among all breast cancer patients treated during this same time period.


RESULTS
Using previously published clinical and preclinical data, we then hypothesize possible mechanisms for this striking interaction.


CONCLUSIONS
Increased awareness of potential interactions between targeted agents and radiation to the brain is crucial.
Julie A
JA
Carlson
Zohra
Z
Nooruddin
Chad
C
Rusthoven
Anthony
A
Elias
Virginia F
VF
Borges
Jennifer R
JR
Diamond
Brian
B
Kavanagh
Peter
P
Kabos
D000080044:Ado-Trastuzumab Emtansine; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D001929:Brain Edema / Q000209:etiology* / Q000473:pathology; D001932:Brain Neoplasms / Q000556:secondary* / Q000628:therapy*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003131:Combined Modality Therapy / Q000009:adverse effects; D005260:Female; D006801:Humans; D008453:Maytansine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008875:Middle Aged; D009336:Necrosis / Q000209:etiology; D016634:Radiosurgery / Q000009:adverse effects*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D000068878:Trastuzumab
D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008453:Maytansine; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human