Pancreatic Stereotactic Body Radiotherapy: Safety Concerns
pancreatic SBRT Shows Promising Survival, But Late GI Toxicity Remains a Concern
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New research highlights the survival benefits of Stereotactic Body Radiation Therapy (SBRT) for pancreatic cancer, while also underscoring the importance of managing late gastrointestinal (GI) toxicity, particularly in patients who have not undergone prior surgery.
A recent study published in the Journal of the National Comprehensive Cancer Network investigated the outcomes of patients with unresectable or medically inoperable pancreatic cancer treated with SBRT. The findings reveal a median overall survival of 18 months for the entire cohort, with a median follow-up of 21.2 months from the end of SBRT.
Key Findings from the Study
The study’s “TAKEAWAY” section provides critical insights into the efficacy and safety of pancreatic SBRT.
Survival and Early Mortality
Median Overall Survival: The full cohort of patients achieved a median overall survival of 18.0 months.
Early Mortality: Within 90 days of receiving SBRT, 7.5% of patients (n = 38) died.The primary cause of these early deaths was disease progression (47.3%).Infection accounted for 18.4% of early deaths (n = 7), with six deaths attributed to infection and one to pulmonary embolism. The causes of death for the remaining 13 patients were unknown.
Hospitalizations and Toxicity
Hospital Admissions: Nearly a quarter of patients (24.3%) required hospitalization within 90 days of SBRT.Infections were the most frequent reason for admission, followed by acute GI toxicity.
Late GI Toxicity: Among patients with sufficient follow-up to assess late GI toxicity, the crude rate of grade 3 or higher radiation therapy-attributed toxicity was 13.3%. Specific severe GI complications included upper GI bleeding (32 patients), radiation enteritis (11 patients), pseudoaneurysm (8 patients), and fistula (3 patients). The median time to the onset of high-grade GI bleeding was 10.9 months.
Factors Influencing Toxicity
Surgical Resection: The study found that surgical resection was associated with a considerably reduced risk of high-grade GI toxicity (hazard ratio, 0.57; P = .047), even after adjusting for SBRT dose.
SBRT Dose: Lower-dose SBRT regimens were linked to a lower risk of severe GI toxicity. the 2-year actuarial risks for high-grade GI toxicity were 25.0% for very high BED (Biologically Effective Dose), 19.4% for high BED, and 16.0% for moderate BED.
Expert Commentary and Clinical Implications
The authors of the study emphasized that pancreatic SBRT is associated with relatively low mortality rates in the initial 90 days post-treatment.However, they also highlighted the notable risks of adverse events, particularly infections and GI toxicity.
“Infections were a major cause of hospital admission,” the authors noted. “Severe gastrointestinal toxicity primarily occurred as a late event and was associated with the absence of prior surgery and the use of high-BED SBRT regimens.”
This suggests that future studies involving dose escalation in SBRT for pancreatic cancer should incorporate long-term follow-up protocols to meticulously monitor patients for the development of late-onset severe gastrointestinal toxicity.
Study Limitations and Future Directions
The researchers acknowledged several limitations in their study, including its retrospective design and a substantial proportion of patients lost to follow-up. Changes in SBRT fractionation (from single and three fractions to five fractions) and evolving chemotherapy regimens may have introduced confounding factors and bias. Moreover, shorter survival in certain patient subgroups coudl potentially lead to an underestimation of late toxicity rates.
Disclosures
The authors reported no funding for the study and declared no relevant conflicts of interest.
SOURCE: Ellsworth SG, et al.Stereotactic Body Radiation Therapy for Unresectable or Medically Inoperable Pancreatic Cancer. journal of the national Comprehensive Cancer Network. Published online July 2023.