In this study the investigators are testing if the addition of Stereotactic Body Radiation therapy (SBRT) prior to surgery improves surgical outcome in patients with borderline resectable or resectable pancreatic cancer (BRPC).
This is a single arm prospective phase I dose escalation radiation study investigating 5-fraction stereotactic radiotherapy prior to planned surgical resection in borderline resectable or resectable pancreatic cancer. Surgical resection is the only potentially curative technique for managing pancreatic cancer. However more than 80% of patients present with disease that cannot be cured with surgical resection. Negative margin (R0 resection), tumour size, absence of lymph nodes metastases are the strongest prognostic indicators for long term survival. Stereotactic body radiation therapy (SBRT) is a radiation technique for pancreatic cancer where an ablative dose of radiotherapy (RT) can be delivered to a small volume targeting the at risk surgical margin in a short time (1 week versus 5-6 weeks for standard radiotherapy), achieving much higher biologically equivalent dose (BED) (100Gy versus 50Gy) than conventionally fractionated radical RT. The short time of delivery and minimal acute toxicity makes this an attractive treatment option in BPRC as offers the opportunity to integrate systemic treatment. With standard fractionation schedules larger volumes of normal tissue are usually irradiated than with SBRT and an effective dose is limited by toxicity despite the use of Intensity Modulated RT. This study builds on the current evidence base in SBRT pancreas, which has so far been largely used in the locally advanced setting with promising results and aims to take it a step further. This study aims to test the safety and benefit of pre-operative SBRT, delivering very high local doses to the at risk surgical margin which is usually around the main vessels in the retroperitoneum. The concept of margin-intensive therapy is novel, and aims to deliver a higher radiation dose while limiting toxicity to organs at risk.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
The investigators expect to need a maximum of 3 dose levels investigating dose to the area at risk of involved resection lines and to the tumour bed to assess the tolerability of SBRT in this setting. Patient entry will commence at level 1. There is the option to de-escalate to Level -1 should 2 or more DLTs be observed at the starting level. SBRT will not be escalated above level 3. Level -1: Tumour (PTV) 6Gy/# (total dose 30Gy). Area at risk of R1 (PTV\_R) 8Gy/# (total dose 40Gy) Level 1: Tumour (PTV) 6Gy/# (total dose 30Gy). Area at risk of R1 (PTV\_R) 9Gy/# (total dose 45Gy) Level 2: Tumour (PTV) 6.5Gy/# (total dose 32.5Gy). Area at risk of R1 (PTV\_R) 9.5Gy/# (total dose 47.5Gy) Level 3: Tumour (PTV) 7Gy/# (total dose 35Gy). Area at risk of R1 (PTV\_R) 10Gy/# (total dose 50Gy)
The Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
St James' Hospital
Leeds, United Kingdom
Northern Centre for Cancer Care, The Freeman Hospital
Newcastle, United Kingdom
City Hospital
Nottingham, United Kingdom
Maximum tolerated dose (MTD)
The maximum tolerated dose (MTD) is defined as the highest dose of margin-intensive SBRT delivered pre-operatively at which no more than 1 of 6 patients or 0 of 3 patients experiences a dose limiting toxicity (DLT)
Time frame: 30 days from SBRT day 1
Definitive resection rate
Time frame: Surgery
R0/R1/R2 resection margin rates
Time frame: Pathological specimen evaluated at surgery
Rate of pathological complete response
Time frame: Pathological specimen evaluation post operation
Any Late GI AE/other AE > grade 2 CTCAE v4.03
Time frame: >1 month to 6 months post-surgery
Overall survival and progression free survival at 12 and 24 months post D1 SBRT
Time frame: 12 and 24m FU
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The Churchill Hospital, Oxford University Hospitals Trust
Oxford, United Kingdom