From the Journals

Antiangiogenics linked to fatal bleeds after RT in patients with “ultracentral” lung tumors



In patients with tumors bordering the central airway, use of antiangiogenic agents has been linked to fatal hemorrhage after radiation treatment, according to investigators reporting a large, retrospective case series.

Most hemorrhagic events in these patients with so-called “ultracentral” lung tumors occurred in those who received bevacizumab or pazopanib within 30 days of stereotactic body radiation therapy (SBRT), according to radiation oncologist Abraham J. Wu, MD, and coinvestigators at Memorial Sloan Kettering Cancer Center in New York.

Based on these new data, the combination of antiangiogenic agents (AAAs) and SBRT should be avoided in patients with ultracentral lung tumors, the researchers wrote.

“Although this report is limited by its retrospective nature, these findings strongly suggest that AAAs potentiate severe SBRT-related toxic effects,” Dr. Wu and coinvestigators wrote in a report on the study in JAMA Oncology. While AAAs are not indicated for treatment of patients with early-stage lung cancer, they may be used to treat oligometastatic disease, which may also be treated with SBRT.

The study included 88 patients with a median age of 74 years who had a lung tumor abutting the proximal bronchial tree, a planned target volume overlapping the esophagus, or both. There were lung metastases in 35 patients.

Nine patients had received bevacizumab, pazopanib, or ramucirumab, stopping a median of 30 days prior to SBRT and resuming a median of 29 days after the end of the radiation treatment.

There were six fatal pulmonary hemorrhages in 19.6 months of follow-up, Dr. Wu and coinvestigators reported. Of those six patients, four had received an antiangiogenic agent (three bevacizumab, one pazopanib) within 30 days of SBRT.

The probability of fatal pulmonary hemorrhage was significantly higher in the patients receiving AAAs versus those who did not (hazard ratio, 16.9; 95% confidence interval, 3.2-88.8; P less than .001).

Another six patients received AAAs more than 90 days before or after SBRT, and none of them had fatal hemorrhages.

A high rate of fatal hemorrhage was reported in another recent study of patients with ultracentral lung tumors, but that study did not identify any risk factors related to this toxic effect, Dr. Wu and coauthors wrote.

The research was partly supported by the National Institutes of Health, the China Scholarship Council, and the Joanne & John Dallepezze Foundation. The investigators reported disclosures related to AstraZeneca, CivaTech Oncology, Alpha Tau Medical, Varian Medical Systems, Boehringer Ingelheim, Pfizer, Merck, and Elekta.

SOURCE: Wu AJ et al. JAMA Oncol. 2019 Apr 4. doi: 10.1001/jamaoncol.2019.0205.

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