Additional Treatment for Isolated Local Pancreatic Cancer Recurrence Using Stereotactic Body Radiation Therapy

A Randomized Controlled Trial on Additional Treatment for Isolated Local Pancreatic Cancer Recurrence Using Stereotactic Body Radiation Therapy

A randomized controlled trial, nested within an existing prospective cohort (Dutch Pancreatic Cancer Project; PACAP) according to the 'trials within cohorts' (TwiCs) design in which the effect of additional local ablative therapy compared to current standard of care alone, on survival after recurrence in patients with isolated local pancreatic ductal adenocarcinoma (PDAC) recurrence. The most important secondary endpoint is quality of life. Other secondary endpoints are treatment response, acute and late toxicity, overall survival, progression-free survival, local progression-free survival, distant metastases free survival and reasons for non-eligibility or exclusion.

Rationale: Disease recurrence remains the main cause of mortality in patients who underwent resection for PDAC. In case of recurrence, patients are currently treated with palliative chemotherapy or best supportive care. In 20-30% of all patients, isolated local PDAC recurrence occurs after resection, which is frequently associated with considerable morbidity from local destructive tumor growth. Although survival after recurrence is predominantly determined by systemic disease, additional local ablative therapy might be of value to improve local disease control in these patients, which could positively affect survival and quality of life (QoL). Previously, radiation therapy has played only a minor role in the treatment of PDAC. As the pancreas is tightly surrounded by organs with limited radiation dose tolerance and subjected to abdominal motion due to respiration and peristalsis, optimal dose delivery has been impeded with conventional radiotherapy techniques. The development of image-guided stereotactic body radiation therapy (SBRT) techniques, however, enabled safe delivery of high irradiation doses to pancreatic lesions. Early retrospective studies have suggested that SBRT might lead to improved local control in patients with isolated local PDAC recurrence, potentially having a beneficial effect on both survival and QoL. In the current, multicenter randomized controlled trial, the value of SBRT in addition to standard of care in patients with isolated local PDAC recurrence is compared to standard of care alone, with regard to both survival and quality of life outcomes.

Objective: The main objective of this study is to improve survival after recurrence in patients with isolated local PDAC recurrence using local ablative treatment with SBRT in addition to standard of care. Furthermore, the effects of additional SBRT on QoL will be evaluated within this study.

Study design: A randomized controlled trial, nested within a prospective cohort (PACAP) according to the TwiCs design.

Study population: PACAP-participants with isolated local PDAC recurrence after primary resection who provided informed consent for being randomized in future studies.

Intervention: Local ablative therapy (5 times 8 Gray SBRT) in addition to standard of care.

Comparison: standard of care.

Main study endpoints: The main study endpoint is survival after recurrence. The most important secondary endpoint is quality of life. Other secondary endpoints are radiological treatment response, acute and late toxicity, overall, progression-free, local progression-free and distant metastasis free survival and reasons for non-eligibility or exclusion.

Inclusion Criteria:

• Participation in the PACAP cohort with written informed consent for being randomized in future studies
• Isolated local recurrence after primary PDAC resection
• Minimum age of 18 years

Exclusion Criteria:

• Distant metastases
• Expected lifespan < 3 months
• Ineligibility for MRI or CT according to the protocol of the local radiology department;
• Highly selective cases with resectable, isolated local recurrence without the need for either systemic or local ablative induction therapy, eligible for re-resection according to the expert panel.