Introduction

Pancreatoblastoma is an extremely rare pediatric pancreatic tumor, occurring in <1 in 10 million individuals [1]. It primarily affects children <10 years of age, with a mean age of onset of 5 years [2]. Pancreatoblastoma is believed to arise from the remnants of fetal pancreatic acinar cells, with tumor development linked to the activation of the Wnt/β-catenin and insulin-like growth factor 2 signaling pathways [3]. We analyzed pediatric pancreatic tumors using data from a population-based cohort collected from the Surveillance, Epidemiology, and End Results database between 1975 and 2018. Pancreatoblastoma accounted for 11.3% of the 195 cases and occurred more frequently in young children [4].

The main treatment for pancreatoblastoma is surgical resection, because complete removal of the primary tumor is associated with a significantly better prognosis than conventional pancreatic cancer. However, invasion of the splenic vein, superior mesenteric artery, duodenum, or lymph nodes has been identified as a key risk factor for pancreatoblastoma and is associated with incomplete resection [5]. Multidisciplinary treatment approaches, including chemotherapy and radiotherapy, are essential for clinical management, and risk factors should be considered in therapeutic planning before surgery. Preoperative chemotherapy is recommended to reduce the volume of non-resectable tumors at diagnosis [6].

Despite advances in our current understanding of the risk factors and treatment strategies, the role of radiotherapy in the management of pancreatoblastoma remains unclear. To address this gap, a comprehensive review of the current evidence addressing the use of radiotherapy, particularly in terms of appropriate dose and fractionation, is warranted to determine its potential role in treatment protocols and to optimize disease management.

Methods

A quantitative literature search of the PubMed database using the key terms “Pancreatoblastoma” AND (“RADIOTHERAPY” OR “RADIATION THERAPY”) for relevant studies published from January 1986 to November 2024 was performed in December 2024. The inclusion criteria were case reports and case series that explicitly confirmed the use of radiotherapy for the treatment of pancreatoblastoma. Owing to the rarity of this disease, to the best of our knowledge, no large-scale studies of radiotherapy in pancreatoblastoma have been reported as of December 2024.Patients for whom radiotherapy was not specified were excluded. In addition, review articles and reports with unclear clinical descriptions were excluded to ensure accuracy and avoid duplication.

Thirty-six records were retrieved from the initial literature search (Fig. 1). Following the initial screening, 19 records were excluded for reasons such as lack of institutional access, absence of a digital object identifier, and classification as a review article. As a result, 17 case reports underwent further detailed assessment. During the detailed review, 10 additional studies were excluded because they either did not provide evidence of radiotherapy use or lacked radiation dose data. Ultimately, seven case reports were included in this study.

Results

Seven case reports comprising eight patients were included in the analysis. A flow diagram illustrating the study selection process is shown in Fig. 1. Stereotactic radiotherapy was used in two cases as an adjuvant therapy for distant intracranial metastases [7,8]. Although this approach is not specific to pancreatoblastoma, it is widely accepted for the management of brain metastases. Stereotactic radiotherapy represents a recent development in radiation therapy [9]. Stereotactic radiotherapy after resection of brain metastases has been shown to be a useful recurrence-preventive treatment with fewer side effects than whole-brain irradiation [10]. In the cases analyzed, postoperative stereotactic radiotherapy was administered at 25 Gy in five fractions and 18 Gy in one fraction.

Patient characteristics and radiation doses administered to the remaining six patients are summarized in Table 1. Excluding intraoperative radiation therapy, the median external radiation dose was 40 Gy (range, 36–46.2 Gy). Intraoperative radiation therapy was administered in two cases at doses of 15 Gy and 20 Gy.

Souzaki et al. [11] reported a case involving a 6-year-old girl who presented with a bulky pancreatic mass, for which initial resection was deemed impossible. After five cycles of induction chemotherapy, the patient underwent radiotherapy (40 Gy) in combination with chemotherapy and stem cell transplantation. Subsequently, a definitive pylorus-preserving pancreaticoduodenectomy was performed to achieve complete tumor resection.

Mumme et al. [12] described a case involving a 22-year-old female treated using a multimodal approach. Radiotherapy included an intraoperative dose of 15 Gy and postoperative computed tomography (CT)-guided three-dimensional conformal radiotherapy, with a total dose of 36 Gy delivered in fractions of 1.8 Gy each. Combined with chemotherapy, this approach enabled complete tumor resection. The treatment was well tolerated, with no significant adverse effects such as myelosuppression or mucositis. The patient has remained recurrence-free for 9 months after treatment.

Murakami et al. [13] reported a case involving a 5-year-old boy who underwent initial tumor resection complicated by spillage, followed by postoperative radiotherapy with 40 Gy delivered in 20 fractions over a period of 4 weeks combined with chemotherapy. Subsequently, the locally recurrent tumor was treated by incomplete resection and intraoperative radiotherapy at 20 Gy. The patient remained disease-free for 3 years and 8 months after treatment.

Vannier et al. [14] reported two pediatric cases of pancreatoblastoma treated with a combination of chemotherapy and radiotherapy. In the first case, the tumor was initially localized to the body and tail of the pancreas and local resection was performed, which was considered incomplete. Radiotherapy was subsequently delivered using an 18-MeV linear accelerator, with 40 Gy administered to the tumor bed and 30 Gy to the pancreatic head and right lobe of the liver. The patient remained tumor-free and was in first remission 40 months after treatment completion. In the second case, radiotherapy was administered as a consolidation therapy following salvage chemotherapy for the relapsed tumor. A total dose of 36 Gy was delivered to the initial tumor bed and recurrence fields. However, 7 months after therapy, a second relapse involving the supraclavicular lymph node and liver occurred.

Griffin et al. [15] reported a case involving a 3-year-old girl with recurrent pancreatoblastoma, who was successfully treated with radiotherapy after experiencing two local recurrences. The second recurrence was managed solely with radiotherapy, resulting in significant tumor regression, as observed on CT after treatment completion. Radiotherapy targeted the primary and recurrent tumor volumes, delivering a total dose of 46.2 Gy in 28 fractions over 7 weeks using a 4-MeV linear accelerator. The patient was disease-free 2 years after treatment.

Discussion

The efficacy of radiotherapy for treating pancreatoblastoma remains unclear. The European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) analyzed cases from Italy’s national groups between 2000 and 2009 [16]. Among the 20 patients aged <18 years (median age, 4 years), nine had distant metastases at diagnosis. Seventeen patients underwent tumor resection, 18 received chemotherapy, and seven underwent radiotherapy (35%). The reported 5-year event-free survival rate was 58.8%, and the overall survival rate was 79.4%.

Dhebri et al. [17] examined various treatment modalities in 116 patients diagnosed with pancreatoblastoma. Surgical resection was performed in 96 (81%), chemotherapy in 62 (53%), and radiotherapy in 24 (21%) patients. Radiotherapy was used as an adjunct to surgery in 22 patients and unresectable disease in two. The 5-year survival rate of the patients who received adjuvant radiotherapy was 60%.

Yin et al. [18] highlighted the differences in treatment strategies between adult pancreatoblastoma and pancreatic ductal adenocarcinoma. Chemotherapy use was similar between the groups, with rates of 60.9% and 70.7%, respectively; however, radiotherapy was significantly less frequently utilized in patients with pancreatoblastoma (4.8% compared with 37%). These findings emphasize the need for further research to optimize the treatment strategies for pancreatoblastoma across different age groups.

The role of radiotherapy in pediatric pancreatoblastoma remains unclear. According to the EXPeRT, radiotherapy may be recommended after macroscopically incomplete surgery or recurrence [19]. It may also be considered in patients with positive surgical margins, lymph node involvement, or tumor spillage. However, the long-term side effects in young children require careful consideration.

Although cisplatin and doxorubicin are commonly used, there is no consensus on adjuvant chemotherapy regimens for pancreatoblastoma. Recently, Leng et al. [20] demonstrated the efficacy of surufatinib, a tyrosine kinase inhibitor, in achieving progression-free survival for ≥14 months and enabling surgical resection of liver metastases in a 27-year-old patient diagnosed with pancreatoblastoma.

Meneses et al. [21] proposed stem cell transplantation as a strategy for incomplete resection without radiotherapy in microscopic residual disease. In one case, a 14-year-old girl underwent preoperative chemotherapy followed by surgery with microscopic margins, postoperative chemotherapy, and high-dose chemotherapy with autologous hematopoietic stem cell transplantation. Four years later, the patient remained disease-free.

Conclusion

Radiotherapy has emerged as a valuable component of multidisciplinary management of pancreatoblastoma, particularly in cases of incomplete resection or tumor recurrence. Although surgical resection remains the cornerstone of therapy, incomplete resection is clearly associated with poor prognosis. Dhebri et al. [17] analyzed 153 patients with pancreatoblastoma and reported an overall 5-year survival rate of 50%, with non-resectable disease at presentation associated with a significantly worse prognosis (p<0.001). Bien et al. [19] found that the 5-year event-free survival rate in patients with complete (R0) primary or delayed resection was 75.0% compared to only 28.6% in those who did not undergo complete tumor resection. For patients with incomplete resection, despite the limited follow-up period in studies to date, our findings indicate that the addition of radiotherapy may provide effective disease control. However, the number of cases included in this review was limited, and the treatment regimens and evaluation criteria varied across the different studies. Therefore, the efficacy of radiotherapy demonstrated in this review remains hypothetical, and the level of evidence is limited. Further prospective studies with larger patient cohorts and standardized protocols are needed to establish definitive evidence for the role of radiotherapy in pancreatoblastoma management.

However, the potential long-term side effects of radiotherapy, especially in pediatric patients, must be carefully weighed against its benefits. The rarity of pancreatoblastoma has limited large-scale studies, leaving gaps in our current understanding of the optimal dose, fractionation, and timing of radiotherapy. Future research should focus on refining radiotherapy protocols, evaluating their integration with emerging therapies, such as targeted agents and immunotherapy, and developing age-appropriate treatment strategies to minimize toxicity. Radiotherapy remains an essential but underutilized tool for the treatment of pancreatoblastoma, with the potential for broader applications in well-defined clinical settings.

Article information

Conflicts of interest

No potential conflict of interest relevant to this article was reported.

Funding

None.

Fig. 1.

Flow diagram illustrating the study selection process for case reports addressing radiotherapy in pancreatoblastoma. A total of 36 studies were initially retrieved from a search of the PubMed database using specific keywords. The exclusion criteria are lack of access, absence of a digital object identifier, and review articles, resulting in 17 eligible case reports. These were further assessed, with additional exclusions made for studies lacking radiation dose or radiation use data, leaving seven case reports included in the study analysis.

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