Pancreatic cancer remains one of the most difficult malignancies to treat, particularly when patients present with borderline resectable or locally advanced disease. In these cases, surgery is often not immediately possible because of vascular involvement, and the central challenge becomes how to convert more patients to safe, margin-negative resection while controlling early disease progression.
A new prospective study published in Advances in Radiation Oncology evaluated whether introducing stereotactic body radiotherapy early in the neoadjuvant sequence could strengthen disease control when followed by chemoimmunotherapy.
The study, titled “Neoadjuvant Early Stereotactic Body Radiotherapy Followed by Chemoimmunotherapy in Borderline Resectable and Locally Advanced Pancreatic Cancer,” examined nab-paclitaxel and gemcitabine plus camrelizumab, with or without early SBRT, in patients with previously untreated borderline resectable pancreatic cancer or locally advanced pancreatic cancer.
Why the Timing of Radiotherapy Matters
Neoadjuvant therapy has become an important strategy in pancreatic cancer because it may treat micrometastatic disease early, improve the chance of later surgery, and help identify patients whose disease biology is too aggressive for immediate operative management.
Chemotherapy combinations such as FOLFIRINOX and nab-paclitaxel plus gemcitabine have shown activity in this setting. Radiotherapy, including SBRT, has also been incorporated into neoadjuvant treatment strategies. However, its role remains debated, especially after mixed results from prior trials.
The question is no longer only whether radiotherapy should be used. Increasingly, the question is when it should be used.
Most previous neoadjuvant strategies have delivered radiotherapy concurrently with systemic therapy or after induction chemotherapy. This study explored a different approach: giving SBRT first, then moving quickly into chemoimmunotherapy.
A Prospective Study in a High-Risk Population
The single-center, prospective, open-label, nonrandomized trial enrolled 22 adults with treatment-naive borderline resectable or locally advanced pancreatic ductal adenocarcinoma.
Patients were assigned to one of two cohorts:
An SBRT cohort receiving early SBRT at 25 Gy in 5 fractions, followed by nab-paclitaxel, gemcitabine, and camrelizumab.
A non-SBRT cohort receiving the same chemoimmunotherapy regimen without radiotherapy.
Each cohort included 11 patients. The chemotherapy backbone consisted of nab-paclitaxel 125 mg/m² and gemcitabine 1000 mg/m² on days 1 and 8 of a 3-week cycle. Camrelizumab was administered at 200 mg every 3 weeks.
In the SBRT cohort, chemoimmunotherapy began within one week after completion of SBRT. Patients were reassessed every 6 to 8 weeks, and surgical eligibility was determined by a multidisciplinary team.
The primary endpoint was objective response rate. Secondary endpoints included disease control rate, R0 resection rate, downstaging, progression-free survival, overall survival, locoregional failure-free survival, distant metastasis-free survival, and safety.
Disease Control Was Achieved in All Patients
Across the full study population, the objective response rate was 36.4%, with 8 of 22 patients achieving a partial response. No complete responses were reported.
The disease control rate was 100%, with all patients achieving either partial response or stable disease. Objective response rates were identical between the two cohorts, with 4 patients in each group achieving partial response.
Although response rates were similar, time-to-event outcomes suggested a potential advantage for early SBRT.
With a median follow-up of 30.0 months, median progression-free survival was 12.5 months in the SBRT cohort compared with 6.6 months in the non-SBRT cohort. This exploratory between-cohort comparison reached statistical significance.
Median overall survival was 20.8 months in the SBRT cohort and 13.9 months in the non-SBRT cohort. The difference was not statistically significant.
Surgery After Neoadjuvant Therapy
After neoadjuvant treatment, 7 patients were considered resectable by the multidisciplinary team. One patient declined surgery, and 6 ultimately underwent resection.
All 6 resected patients achieved clinical-to-pathologic downstaging and R0 margins. Four of these surgeries occurred in the SBRT cohort, and two occurred in the non-SBRT cohort.
This finding is notable because margin-negative resection remains one of the key goals in borderline resectable and locally advanced pancreatic cancer. Although the number of surgical patients was small, the consistency of R0 resection among those who underwent surgery supports the feasibility of the approach.
Early SBRT May Improve Local Disease Control
The exploratory failure-pattern analysis offered another important signal.
Median locoregional failure-free survival was 18.9 months in the SBRT cohort compared with 8.1 months in the non-SBRT cohort. This suggests that the improvement in progression-free survival may have been driven, at least in part, by stronger local disease control.
Median distant metastasis-free survival was 12.5 months in the SBRT cohort and 9.6 months in the non-SBRT cohort, with no significant difference between groups.
This pattern is clinically relevant. In pancreatic cancer, systemic progression is common, but uncontrolled local disease can also cause major morbidity and may prevent later surgical opportunities. A short-course, early SBRT strategy may help consolidate local control without delaying systemic therapy for long.
CA19-9 Decline Provided an Additional Signal
The study also explored CA19-9 dynamics during neoadjuvant therapy.
A decline of at least 50% in CA19-9 was observed in 81.8% of patients in the SBRT cohort and 63.6% of patients in the non-SBRT cohort.
In the overall cohort, patients with a CA19-9 decline of at least 50% had longer median progression-free survival and locoregional failure-free survival than those with a smaller decline. However, this association was not significant within individual cohorts, likely reflecting the small sample size.
The finding supports the continuing interest in CA19-9 as a practical marker of treatment response in pancreatic cancer, while also underscoring the need for stronger biomarker-driven studies.
Safety Was Manageable
The treatment strategy showed acceptable tolerability.
Treatment-related adverse events occurred in 95.5% of patients. Grade 3 or higher treatment-related adverse events occurred in 36.4% of patients, with equal frequency in the SBRT and non-SBRT cohorts.
The most common all-grade adverse events included anemia, leukopenia, thrombocytopenia, and nausea or vomiting. The most common grade 3 or higher events were leukopenia and neutropenia.
No treatment-related deaths were reported. Importantly, no grade 3 or higher acute luminal gastrointestinal toxicity was observed in the SBRT cohort.
Among the 6 patients who underwent surgery, postoperative complications were limited to Clavien–Dindo grade 1–2 events. No grade 3 or higher postoperative complications and no surgery-related deaths occurred.
A Feasible Strategy, But Not Yet Definitive
The study provides preliminary prospective evidence that early SBRT followed by chemoimmunotherapy is feasible in borderline resectable and locally advanced pancreatic cancer. The longer progression-free survival and locoregional failure-free survival observed in the SBRT cohort are encouraging.
However, the findings must be interpreted carefully.
The trial was single-center and nonrandomized. Treatment allocation was based on patient preference and multidisciplinary team decision, which introduces potential selection bias. The sample size was small, with only 22 patients overall and 11 patients in each cohort. Between-cohort comparisons were exploratory rather than definitive.
There were also baseline imbalances between cohorts, including differences in tumor location and the proportion of patients with locally advanced disease. These factors may have influenced outcomes.
For these reasons, the results should be viewed as hypothesis-generating. Larger randomized studies will be needed to determine whether early SBRT truly adds benefit to neoadjuvant chemoimmunotherapy and to identify which patients are most likely to benefit.
What This Study Adds
This study addresses an important question in pancreatic cancer treatment: whether radiotherapy should be moved earlier in the neoadjuvant sequence.
The approach is biologically plausible. Radiotherapy may remodel the tumor microenvironment, promote antigen release, and potentially improve sensitivity to immunotherapy. SBRT also offers a short treatment course, allowing rapid transition to systemic therapy.
In this study, early SBRT was completed within one week, followed promptly by chemoimmunotherapy. Compliance was high, toxicity was manageable, and local disease-control signals were encouraging.
For a disease where treatment progress remains difficult, even early signals matter. This study does not establish a new standard of care, but it adds meaningful prospective evidence to an evolving field and supports further investigation of radiotherapy sequencing in pancreatic cancer.
Title: “Neoadjuvant Early Stereotactic Body Radiotherapy Followed by Chemoimmunotherapy in Borderline Resectable and Locally Advanced Pancreatic Cancer”
Authors: Shuhan Zhao, Jing Tang, Xin Li, Tao Yin, ShanMiao Gou, Jing Wang, Zhenyu Lin, Jianli Hu, Hongli Liu, Xiaoxue Gou, Heshui Wu, Tao Zhang, Jun Xue
Journal: Advances in Radiation Oncology
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