Increased bowel toxicity in patients treated with a vascular endothelial growth factor inhibitor (VEGFI) after stereotactic body radiation therapy (SBRT).
OBJECTIVE
Gastrointestinal injury occurs rarely with agents that affect the vascular endothelial growth factor receptor and with abdominal stereotactic body radiation therapy (SBRT). We explored the incidence of serious bowel injury (SBI) in patients treated with SBRT with or without vascular endothelial growth factor inhibitor (VEGFI) therapy.


METHODS
Seventy-six patients with 84 primary or metastatic intra-abdominal lesions underwent SBRT (median dose, 50 Gy in 5 fractions). Of the patients, 20 (26%) received VEGFI within 2 years after SBRT (bevacizumab, n=14; sorafenib, n=4; pazopanib, n=1; sunitinib, n=1). The incidence of SBI (Common Terminology Criteria for Adverse Events, version 4.0, grade 3-5 ulceration or perforation) after SBRT was obtained, and the relationship between SBI and VEGFI was examined.


RESULTS
In the combined population, 7 patients (9%) had SBI at a median of 4.6 months (range, 3-17 months) from SBRT. All 7 had received VEGFI before SBI and within 13 months of completing SBRT, and 5 received VEGFI within 3 months of SBRT. The 6-month estimate of SBI in the 26 patients receiving VEGFI within 3 months of SBRT was 38%. No SBIs were noted in the 63 patients not receiving VEGFI. The log-rank test showed a significant correlation between SBI and VEGFI within 3 months of SBRT (P=.0006) but not between SBI and radiation therapy bowel dose (P=.20).


CONCLUSIONS
The combination of SBRT and VEGFI results in a higher risk of SBI than would be expected with either treatment independently. Local therapies other than SBRT may be considered if a patient is likely to receive a VEGFI in the near future.
Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA. barney.brandon@mayo.edu
Brandon M
BM
Barney
Svetomir N
SN
Markovic
Nadia N
NN
Laack
Robert C
RC
Miller
Jann N
JN
Sarkaria
O Kenneth
OK
Macdonald
Heather J
HJ
Bauer
Kenneth R
KR
Olivier
D000008:Abdominal Neoplasms / Q000000981:diagnostic imaging / Q000601:surgery*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D000068258:Bevacizumab; D004378:Duodenal Diseases / Q000209:etiology; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000009:adverse effects; D007410:Intestinal Diseases / Q000209:etiology*; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000009:adverse effects; D011743:Pyrimidines / Q000009:adverse effects; D011758:Pyrroles / Q000009:adverse effects; D011859:Radiography; D016634:Radiosurgery / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D000077157:Sorafenib; D013276:Stomach Ulcer / Q000209:etiology*; D013449:Sulfonamides / Q000009:adverse effects; D000077210:Sunitinib; D014456:Ulcer / Q000209:etiology*
D061067:Antibodies, Monoclonal, Humanized; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D009536:Niacinamide; D000068258:Bevacizumab; C516667:pazopanib; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib