A groundbreaking new study known as TORPEDO is currently redefining the therapeutic landscape for patients diagnosed with inoperable, non-metastasized pancreatic ductal adenocarcinoma (PDAC). This malignancy is notorious for its aggressive nature, with late symptom onset and high mortality rates. Radical surgical resection remains the gold standard curative option—yet the majority of patients present with locally advanced disease characterized by extensive vascular involvement, rendering them unsuitable for surgery. The TORPEDO trial investigates the efficacy of integrating stereotactic body radiation therapy (SBRT) into the treatment paradigm, aiming to improve survival and local tumor control beyond what is achievable with chemotherapy alone.
Pancreatic cancer constitutes one of the most formidable oncologic challenges, often detected when tumors have infiltrated critical vascular structures that complicate surgical intervention. Accordingly, systemic chemotherapy is typically the frontline treatment to address microscopic metastatic disease and palliate symptoms. Despite advances, locoregional progression remains a significant cause of morbidity, negatively impacting patients’ quality of life due to pain, biliary obstruction, and other complications. Conventional chemoradiotherapy approaches have yielded inconsistent results, highlighting the urgent need for innovative regimens that can offer better local control while maintaining tolerable toxicity profiles.
TORPEDO represents a rigorously designed, multicenter randomized phase II clinical trial that targets this unmet need. Specifically, it enrolls patients with locally advanced PDAC who are not candidates for immediate surgery, as well as those with borderline resectable tumors who are medically unable or unwilling to undergo resection. The study’s premise is to evaluate whether the strategic addition of SBRT—an advanced form of high-precision radiation delivered in hypofractionated doses—after induction chemotherapy leads to meaningful improvements in progression-free survival and overall outcomes compared to continued chemotherapy alone.
The clinical trial protocol stipulates an initial 12-week induction chemotherapy phase, utilizing commonly adopted regimens such as modified FOLFIRINOX or gemcitabine combined with nab-paclitaxel. These treatments aim to reduce tumor burden, eradicate micrometastases, and select patients with stable disease devoid of distant metastasis. Only these responders then proceed to the randomization phase where they are assigned either to arm A—with continued chemotherapy—or to arm B, where chemotherapy is followed by the application of SBRT at a dose schedule of 5 fractions of 8 Gy each. This dosing strategy is meticulously calculated to maximize tumor cytotoxicity while sparing adjacent normal tissues.
The primary endpoint of TORPEDO is 2-year progression-free survival, reflecting the trial’s focus on delaying or preventing local tumor progression and distant spread. Secondary endpoints incorporate overall survival metrics, detailed analyses of local and metastasis-free survival timelines, objective response rates evaluated radiographically, surgical outcomes including resectability and R0 resection rates, postoperative complications, toxicity profiles, and patient-reported quality of life measurements. These comprehensive endpoints will collectively elucidate the value of SBRT integration in this challenging patient population.
Reasoned by robust preclinical data and emerging clinical experience, SBRT offers distinct dosimetric and biological advantages over traditional fractionated radiation. It delivers ablative doses with submillimeter precision, guided by advanced imaging technologies that account for respiratory motion and organ displacement. This technological sophistication minimizes radiation exposure to surrounding critical structures such as the duodenum, stomach, and major blood vessels, which is paramount in pancreatic cancer radiotherapy due to inherent anatomical constraints.
From a biological standpoint, hypofractionated SBRT induces enhanced DNA damage, vascular endothelial disruption, and potentially synergizes with systemic chemotherapy to potentiate tumor cell kill. Its shorter treatment duration compared to conventional radiation schedules also minimizes patient inconvenience and allows quicker resumption of systemic therapies. The TORPEDO trial’s investigation of the interplay between radiation dose intensities and resultant clinical outcomes seeks to optimize the therapeutic window for maximum efficacy with tolerable toxicity.
Incorporating a multidisciplinary tumor board to assess tumor resectability after neoadjuvant treatments ensures that surgical options remain viable for select patients, emphasizing an integrative approach. This is crucial because resection with negative margins (R0) continues to be the only curative option, offering the best chance for long-term survival. The trial’s permissive inclusion of borderline resectable cases who decline or cannot undergo surgery reflects real-world clinical scenarios, thereby enhancing the external validity of the results.
Patient quality of life is a significant concern in pancreatic cancer management, given the disease’s symptomatic burden and aggressive course. Effective local tumor control could translate into reduced pain, improved nutrition, and better overall functional status, marking important endpoints beyond classical survival measures. The TORPEDO study includes validated quality-of-life instruments to capture these patient-centered outcomes rigorously.
This study is ethically sanctioned by the GZA Hospitals Ethics Committee as of April 2024 and boasts registration on ClinicalTrials.gov under identifier NCT06691425, ensuring transparency and adherence to international clinical trial standards. Its multicenter design enables enrollment of a diverse patient cohort, enhancing statistical power and generalizability.
Should TORPEDO confirm that SBRT combined with chemotherapy prolongs survival and improves local control, it could establish a new standard of care for a patient population with hitherto limited curative options. This could revolutionize existing treatment algorithms by introducing a more aggressive locoregional approach, challenging the historical nihilism associated with inoperable pancreatic cancer.
Moreover, the findings would stimulate further translational research into radiobiological mechanisms, potentially unveiling biomarkers predictive of response to SBRT. Such advancements could pave the way for personalized radiation oncology strategies and integration with emerging systemic immunotherapies or targeted agents.
In conclusion, the TORPEDO trial embodies a pivotal step toward enhancing the therapeutic arsenal against one of the deadliest malignancies. By combining cutting-edge radiation techniques with effective chemotherapy protocols, it seeks to overcome the formidable challenges of controlling pancreatic adenocarcinoma locally and systemically. The oncology community eagerly awaits the maturation of this trial’s results, anticipating data that could transform clinical practice and improve patient survival and quality of life in this devastating disease.
Subject of Research: Stereotactic body radiation therapy combined with chemotherapy in inoperable, non-metastasized pancreatic ductal adenocarcinoma.
Article Title: Stereotactic body radiation therapy for inoperable non-metastasized pancreatic adenocarcinoma: a randomised phase II study (TORPEDO).
Article References:
Stas, D., Vandamme, T., Roeyen, G. et al. Stereotactic body radiation therapy for inoperable non-metastasized pancreatic adenocarcinoma: a randomised phase II study (TORPEDO). BMC Cancer 25, 1671 (2025). https://doi.org/10.1186/s12885-025-15041-8
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