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

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.

• Patient reported Quality of Life as assessed using Exocrine Pancreatic Insufficiency (EPI) questionnaire [Time frame: At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP-cohort. Assessed through study completion, up to 18 months]
• Patient reported non-disease specific health-related Quality of Life (HRQoL) as assessed using the EQ-5D-5L [Time frame: At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP-cohort. Assessed through study completion, up to 18 months]
• Patient reported cancer-specific HRQoL as assessed using the EORTC QLQ-C30 [Time frame: At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP-cohort. Assessed through study completion, up to 18 months]
• Patient reported tumor-specific HRQoL as assessed using the EORTC LQPAN26 [Time frame: At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP-cohort. Assessed through study completion, up to 18 months]
• Patient reported chemotherapy-induced peripheral neuropathy as assessed using the EORTC QLQ-CIPN20 [Time frame: At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP-cohort. Assessed through study completion, up to 18 months]
• Patient reported Quality of Life as assessed using the happiness, hospital, anxiety and depression scale (HADS) [Time frame: At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP-cohort. Assessed through study completion, up to 18 months]
• Patient reported Quality of Life as assessed using the worry of progression of cancer scale (WOPS) [Time frame: At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP-cohort. Assessed through study completion, up to 18 months]
• Treatment response assessed on CT-imaging (graded according to RECIST guidelines) [Time frame: During and immediately after the intervention (SBRT treatment)]
• Acute and late toxicity of SBRT as assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [Time frame: Through study completion, an average of 18 months]
• Overall survival [Time frame: From the date of primary resection until the date of death from any cause or last follow-up, whichever came first, assessed up to 18 months]
• Progression-free survival [Time frame: From the date of disease recurrence until the date that local and/or distant progression of disease occurs, assessed up to 18 months]
• Local progression-free survival [Time frame: From the date of disease recurrence until the date that locoregional progression of disease occurs, assessed up to 18 months]