Stereotactic Body Radiation Therapy Improves OS for Locally Advanced Pancreatic Cancer

An international systematic review and meta-analysis published in Cancer, titled CRiSP, suggested that stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) may offer a modest improvement in overall survival (OS) compared to conventionally fractioned radiation therapy with concurrent chemotherapy (CFRT), with a more favorable toxicity profile. 

However, the researchers noted that further studies assessing the use of SBRT for patients with LAPC are needed to improve outcomes for this patient population. 

“There is currently no well-defined standard of care in the management of patients with LAPC,” the authors wrote. “This is the first meta-analysis to compare SBRT with CFRT for LAPC.” 

Using a PICOS/PRISMA/MOOSE selection protocol, the researchers identified studies that fit their inclusion criteria. Inclusion criteria included patients diagnosed with locally advanced N0-1 M0 pancreatic cancer, CFRT 1.8 to 2.0 Gy/fraction with chemotherapy per protocol or SBRT ≥5 Gy/fraction in ≤5 fractions, either no control group or another definitive chemotherapy or radiation therapy arm, at least 1 of the outcome measures reported, and single or multi-arm phase II/III prospective study for CFRT and/or phase I/II or retrospective study for SBRT.  

Overall, 470 studies were screened and of those, 9 studies assessed SBRT and 11 assessed CFRT. For SBRT, the median dose was 30 Gy, and the most common regiment was 30 Gy/5 fractions. For CFRT, the doses ranged from 45 to 54 Gy in 1.8- to 2.0-Gy fractions, with the majority of studies administering 50.4 Gy in 28 fractions with concurrent gemcitabine. 

The random effects estimate for 2-year OS was 26.9% (95% CI, 20.6%-33.6%) for SBRT versus 13.7% (95% CI, 8.9%-19.3%) for CFRT and was statistically significant in favor of SBRT. For 1-year OS, the random effects estimate was 53.7% (95% CI, 39.3%-67.9%) for SBRT versus 49.3% (95% CI, 39.3%-59.4%) for CFRT, and was not statistically significant. 

Moreover, the random effects estimate for acute grade 3/4 toxicity was 5.6% (95% CI, 0.0%-20.0%) for SBRT versus 37.7% (95% CI, 24.0%-52.5%) for CFRT and was statistically significant in favor of SBRT. The random effects estimate for late grade 3/4 toxicity was 9.0% for SBRT (95% CI, 3.3%-17.1%) versus 10.1% (95% CI, 1.8%-23.8%) for CFRT, which was not statistically significant. 

“This meta-analysis demonstrates a statistically significant improvement in 2-year OS for patients treated with SBRT compared with CFRT (13.7% vs 26.9%), with lower rates of acute grade 3/4 toxicity (5.6% vs 37.7%) and no difference in late toxicity,” the authors wrote. “When we excluded papers using dose/fractionation schemes, which are now known to be excessively toxic, there was a slightly higher improvement in 2-year OS in the SBRT group relative to the CFRT group (28.6% vs 13.7%, respectively), again with lower rates of acute toxicity (2% vs 37.7% for CFRT, respectively) and no difference in late toxicity.”

According to the researchers, SBRT offers several advantages over CFRT, the first being its short treatment course, given that it is both more convenient for patients and allows for minimal interruptions in the delivery of high-dose systemic chemotherapy, which has previously been found to improve survival in these patients. Further, SBRT is generally well tolerated, with minimal acute toxicity, and may also be more cost-effective than long-course radiation, depending on which conventional radiation technique is used. However, the most significant advantage of SBRT may be its sharp dose fall-off, which allows for dose escalation beyond what can be achieved with conventional radiation techniques. 

“Our study thus serves as a benchmark for further investigation into the use of SBRT for dose escalation, as is currently underway (NCT03621644, ClinicalTrials.gov),” the authors wrote. 

Pancreatic cancer is the third leading cause of cancer death in the US, according to the study, with a 5-year OS of only 9%. And despite advances in both chemotherapy and radiation therapy techniques, the median OS for patients with LAPC is only 12 months.

Reference:

Tchelebi LT, Lehrer EJ, Trifiletti, et al. Conventionally Fractionated Radiation Therapy Versus Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Cancer (CRiSP). Cancer; 2020. doi:10.1002/cncr.32756.