SBRT may increase risk for noncancer death in patients with NSCLC

Stereotactic body radiation therapy appeared to slightly increase risk for noncancer death among patients with non–small cell lung cancer, according to the results of a study presented at the European Society for Therapeutic Radiology and Oncology conference.

This risk appeared greatest when patients received high doses to the left atrium of the heart and the superior vena cava.

“We found that dose to all substructures of the heart were associated with noncancer death for this group of patients,” Barbara Stam, PhD, of the department of radiotherapy at the Netherlands Cancer Institute, said in a press release. “Patients with low doses on the left atrium combined with low doses on the superior vena cava have a higher chance of survival than patients with high doses on the left atrium combined with high doses on the superior vena cava.”

Stam and colleagues sought to investigate noncancer deaths associated with stereotactic body radiation therapy (SBRT) based on the location and dosage of therapy.

The analysis included 565 patients who were treated with cone-beam CT–guided SBRT for early-stage NSCLC.

Using a technique called deformable image registration, researchers mapped heart substructures for individual patients and added radiation doses to determine parameters for various parts of the heart. Based on deformable image registration in 109 patients, researchers created an average heart anatomy to deform the corresponding dose distribution of all patients in the study.

After a median follow-up of 28 months, 58% of patients were alive and 3% had a central tumor.

Multivariate analysis showed statistically significant results for maximum dose to the left atrium (HR = 1.012, P = 0.03) and dose to 2 cc of the superior vena cava (HR = 1.022, P = 0.3).

“Finding if there is a relation between dose to substructures and noncancer death is only relevant if this relation still exists when other factors that are known to be related to noncancer are also taken into account,” Stam said. “Therefore, we performed a second statistical analysis, including factors such as age, lung function and performance status."

In a secondary multivariate analysis — adjusted for performance status, age, sex, biological dose, distance to bronchus, comorbidity index, lung function, tumor diameter, T-stage, institute and smoking pack-years — maximum dose to the left atrium and superior vena cava remained significantly associated with noncancer death.

Researchers also found noncancer death was associated with age (HR = 1.034, P < 0.001), performance status (HR = 1.138, P = 0.004), comorbidity index (HR = 1.125, P = 0.03), lung function (HR = 0.984, P < 0.001) and pack-years smoking (HR = 1.011, P = 0.004).

Overall, each 1-Gy dose above the average 7.9-Gy dose to the left atrium increased risk for noncancer death 1.5%. In other substructures, the risk increased by 1% to 2%.

“Clinically, this could mean that patients might benefit from heart-sparing radiotherapy,” Stam said. “For early-stage lung cancer patients treated with SBRT, we still need to investigate if heart sparing is possible, what compromises need to be made and whether it can increase survival.”

More research about this association is needed, especially about the specific causes of death, according to Philip Poortmans, MD, PhD, head of department of radiation oncology at Radboud University Medical Center in Nijmegen, the Netherlands, as well as president of ESTRO.

“This study confirms that we should take the dose to organs at risk into consideration, not only for malignant lymphoma and breast cancer patients, who are in general younger and have a much longer life expectancy, but also for lung cancer patients when cure is an option,” Poortmans said. “The complex interaction between dose to the heart and comorbidity and age and its influence on noncancer related death remains to be explored in further detail as the excess death rate is seen starting a very short time after treatment, in contrast to the data in lymphoma and breast patients.

“Research into the details of the dose distribution and the (largely unknown) causes of death is required before these results could be translated to the daily clinics’ environment — apart from the advice to keep the dose to the heart as low as possible while maintaining tumor control,” he added. – by Nick Andrews

Reference :

Stam B, et al. Abstract E35-1427. Presented at: ESTRO Conference 35; April 29-May 3, 2016; Turin, Italy.

Disclosure: The study was funded in part by Elekta Oncology Systems LTD and the Dutch Cancer Society.