Abstract
Background
Pancreatic cancer is the 4th deadliest cancer in Canada, with an overall 5-year survival of only 6%. Every year, approximately 4000 Canadians are diagnosed with pancreatic cancer, and only 10–15% of these patients have surgically resectable disease. No satisfactory treatment exists for patients with inoperable locally advanced pancreatic carcinoma. The best survival has been achieved using a combination of chemotherapy and radiotherapy. Conventional radiotherapy has inadequate local disease control as the therapeutic radiation dose to the tumour is limited by the sensitivities of surrounding tissues. Stereotactic body radiotherapy (SBRT) is a minimally invasive treatment technique that allows for ultra-high doses of radiation to be delivered to small areas. The CyberKnife® Robotic Radiosurgery System is a radiation unit designed to deliver SBRT. Fiducial markers placed by endoscopic ultrasound help direct the radiotherapy. It is hypothesized that a higher overall dose of radiation will result in higher rates of local control, and potentially improved survival.
Aims
The goal of this study is to establish the safety and feasibility of using stereotactic body radiotherapy boost technique via CyberKnife in treating unresectable locally advanced pancreatic cancer, as well as to determine the maximal tolerable radiation dose (MTD) of the SBRT boost that can be safely delivered.
Methods
This is a prospective single-arm, single-institution phase I Time-to-event Continual Reassessment Methodology (TITE-CRM) radiation dose escalation trial. This study enrolled patients aged 18–84 with pathologically confirmed pancreatic cancer who were determined to have surgically unresectable disease, with an ECOG ≤2. These patients were treated with SBRT prior to starting conventional radiotherapy, which consisted of a total dose of 45 Gy in 25 fractions over 5 weeks.
Results
Between 2012 and 2018, a total of 11 patients met the eligibility criteria of this study. Their ages ranged from 61 to 84 with a mean of 71.5 years, and they were 64% (7/11) male. At the time of this analysis, 10 of the 11 patients had passed away. The mean and median survival times were 413 days and 313 days, respectively. Three of the patients had significant complications attributed to the radiotherapy, 2 gastric outlet obstructions and 1 deep duodenal ulcer. The doses used ranged from 21 Gy in 3 fractions to 50 Gy in 5 fractions.
Conclusions
This phase 1, single arm study demonstrates that stereotactic body radiotherapy in the treatment of locally advanced, unresectable pancreatic cancer is technically feasible. When combined with conventional radiotherapy, this therapy is generally well tolerated, and can effectively deliver higher doses of radiation to pancreatic malignancies. Doses up to 50 Gy in 5 fractions were tolerated, with the most common dose being 21 Gy in 3 fractions.
Funding Agencies
National Pancreatic Cancer Canada Foundation
Dose escalation of radiation therapy with or without induction chemotherapy for unresectable locally advanced pancreatic cancer
