Pancreatic cancer (PC) has one of the highest mortality rates of any cancer, with an estimated 5-year survival rate of only 11.5% and a complete surgical resection provides the only chance for cure (1). The role of radiotherapy (RT) in the management of PC remains controversial. However, in cases where the tumor is found to be borderline resectable (BRPC) or locally advanced (LAPC), since complete resection with negative surgical margins (R0) may not be possible, emerging evidence suggest a potential role for RT with the aim of improving negative margin rates or reducing the burden of local disease and enhancing local control when surgery is not possible. Neoadjuvant chemoradiotherapy has recently been shown to improve overall survival (OS) when compared to upfront surgery plus adjuvant chemotherapy in patients with resectable and borderline resectable pancreatic cancer (2–4).

Modern advances in RT delivery, particularly stereotactic body RT (SBRT), allow for the precise delivery of a high radiation dose to the target, steep dose gradients beyond the target, as well as reduced overall treatment time (5, 6). However, due in part to the novelty of SBRT in the management of PC, guidelines standardizing optimal patient selection for pancreas SBRT, dosing, simulation technique, and volume delineation are lacking (6). In fact, SBRT was included in the multi-institutional Alliance A021501 phase II trial of neoadjuvant therapy using FOLFIRINOX combined with SBRT versus FOLFIRINOX alone for patients with BRPC and the R0 resection rate was lower in the SBRT arm (7). This study was also associated with low rates of pancreatectomy (35%) and treatment completion (18%) in the SBRT arm, sharply conflicting with the results of many single institution studies of pre-operative SBRT for BRPC and LAPC (8–10). Incorporating pre-operative SBRT followed by surgery in a national study that was performed at small centers with limited experience using this approach instead of limiting the enrollment to high-volume pancreas cancer centers may have impacted on the outcome of this study.

Treatment at higher-volume radiation oncology centers has been associated with improved OS in patients with various cancers (11–15). This association between OS and high-volume centers has also been established in PC resection, with significantly higher mortality rates in patients treated in low-volume centers (16–18). However, the impact of facility volume on OS in patients with PC that receive RT, particularly SBRT, is not well understood. Additionally, despite expanding evidence on the benefits of SBRT in PC in single-institution studies (8, 9, 19), it remains unknown how practice patterns of radiotherapy in BRPC and LAPC are changing in the United States. Ascertaining this information can better characterize the role of RT in PC, as well as identify variations in treatment that can ultimately be addressed to improve care. In the case of pancreatic cancer, where treatment modalities and their outcomes can vary significantly, an examination of these patterns of care can greatly contribute to our understanding and aid in improving treatment strategies.

While high-volume radiation oncology centers are generally linked to better survival outcomes in various cancers (11–15), the impact of facility volume on PC patients, especially in the context of evolving RT practices for BRPC and LAPC in the U.S., remains poorly understood. This study examined how facility volume affects OS in PC patients receiving RT, particularly SBRT. These findings suggest that high-volume centers are associated with improved OS in patients with LAPC or BRPC treated with RT across the United States, as well as characterize some patterns of care of RT in PC.

High-volume RT centers demonstrated superior OS compared to low-volume RT centers (HR 0.863, p<0.001), consistent with other RT studies examining the association of institutional volume with OS (11, 12). This trend highlights the potential benefits of treatment at high-volume centers, which could be due to factors such as higher rates of compliance with national treatment guidelines, more specialization among radiation oncologists leading to increased experience with tumor identification and contouring, more sophisticated motion management and treatment planning techniques, improved multidisciplinary collaboration, more robust RT quality assurance, and a greater availability of experienced diagnostic, therapeutic, and supportive services (15).

These findings are also consistent with the surgical literature that pancreatic cancer resection at high-volume centers is associated with improved survival outcomes (17, 18, 21). In PC, where resection can be complex due to factors such as anatomical positioning, major blood vessel involvement, and late presentation, underscoring the importance of surgeon experience in navigating these high-risk procedures and the enhanced post-operative care and comprehensive ancillary services in high-volume centers (21). Similarly, the complexity of SBRT for PC, characterized by its novelty, technical and planning sophistication, precise targeting, and lack of guideline standardization emphasizes the role of radiation oncologist expertise. In short, the multidisciplinary team experience and specialization that can be found in high volumes centers likely contribute to improved outcomes in patients receiving complex procedures.

Studies in other cancers such as prostate and lung demonstrate exponential growth in the utilization of SBRT over the past two decades (22, 23). This study suggests a similar increase in the utilization of SBRT in PC; from 2004 to 2011, only 8.5% of PC cases were treated with SBRT, however, from 2016 to 2019, 30% of PC cases were treated with SBRT. When stratified by facility volume, SBRT adoption increased across all center types but was most pronounced at high-volume institutions. SBRT use rose from 7.7% to 45.3% in high-volume centers, compared with 5.9% to 20.4% in low-volume centers and 5.2% to 30.9% in intermediate-volume centers (Supplementary Table 1). The slower rise among low- and intermediate-volume centers suggests ongoing disparities in access to SBRT capabilities and experience.

Previous single-institution studies at high-volume centers demonstrate improved OS following neoadjuvant SBRT (8, 9, 19). This study suggests that these findings are consistent among patients treated across the United States, suggesting that there may be improved OS in patients receiving SBRT (HR 0.869, p<0.001) compared to standard fractionation. The Kaplan-Meier curves demonstrate that this trend is not limited to only high-volume centers but is consistent across low- and intermediate-volume centers as well.

Despite the superior OS associated with SBRT, only 17.6% of patients in this study received SBRT, and the majority of these patients were treated in high-volume centers. One explanation could be the extensive multidisciplinary preparation SBRT requires including placing gold fiducial markers endoscopically, high quality treatment planning capabilities, and experienced physicists and radiation therapy staff to implement motion management techniques (24).

The study demonstrated that although low-volume centers utilize SBRT less than high-volume centers, most patients are treated in low-volume RT centers (49.7%). This is a significant finding as it underscores the need to enhance access to treatment options that show significantly improved survival, such as SBRT, in these settings.

In general, our findings suggest that there is a significant increase in OS in patients with PC treated with RT from 2004-2019, across all institutions and treatment types. In addition to more effective chemotherapy regimens such as FOLFIRINOX and gemcitabine/nab-paclitaxel, other contributing factors include advancements in diagnostic techniques, better palliative care, improved chemotherapy and surgery guidelines, as well as advancements in RT such as SBRT.

Despite the large sample size and plethora of variables available through the NCDB, it is limited by its retrospective nature. RT modality was not coded for most patients, hence modality was determined from RT dosing and fractionation. Additionally, the significant underrepresentation of Hispanic patients in our cohort, at only 4.0% versus the national average of 19.1% (25), suggests potential issues in either the NCDB’s ethnicity data collection or access to care at NCDB affiliated centers. This discrepancy is consistent with previous literature, which has documented challenges in accurately capturing ethnicity data from the NCDB, and thus it was excluded from the multivariable analysis (26). Facility-level surgical and radiotherapy volumes are likely correlated in pancreatic cancer, as both treatments are typically concentrated at tertiary centers. While this overlap is unavoidable in real-world data, it should be recognized as a general limitation of national database analyses. The NCDB also does not code for certain factors potentially affecting survival outcomes by radiation facility volume, such as protocol adherence, diagnostic imaging availability, supportive services, and multidisciplinary tumor boards or clinics.

These findings suggest that radiation oncologists’ expertise is critical for providing high-quality RT in PC, especially for SBRT. However, given that most patients receive treatment in low-volume centers, it is crucial to ensure that the high standards of care and treatment protocols established in high-volume centers are consistently implemented in these lower-volume settings.

In conclusion, this study highlights the importance of facility volume in the survival outcomes of PC patients, particularly with the use of SBRT. The increasing adoption of SBRT, its impact on survival, and the current underutilization in lower-volume centers point to the need for broader access to advanced radiation therapies and dissemination of standardized guidelines for contouring, treatment planning and treatment delivery. Educational opportunities should be provided through radiation oncology national societies to ensure that radiation oncologists who may not have training in pancreas SBRT are given the tools they need to incorporate the new techniques into their practices. Incentivizing physicians to pursue further training can be achieved through providing accreditation to radiation oncology sites for specialized techniques such as SBRT based on performance. The observed improvement in survival over time underscores the ongoing advancements in PC treatment, while also indicating areas for future research and guideline development.