Pancreatic
adenocarcinoma remains a lethal malignancy, being the gastrointestinal tumour
with the most sombre prognosis and the fourth most common cause of cancer mortality in
Europe. Surgery is considered the only possible curative treatment option for
these patients although less than 10% of patients are operable at diagnosis. The
role of radiotherapy remains controversial, often used in combination with
chemotherapy in the consolidation of the treatment in locally advanced
pancreatic cancers, resulting in an improved progression free survival (PFS).
Refined radiotherapy
treatment techniques, aiming to improve target definition and motion management,
allowed for an increase in the radiotherapy dose per fraction while limiting
the toxicity to the surrounding tissues.
Stereotactic
body radiotherapy (SBRT) nowadays is considered a treatment option in patients
with locally advanced pancreatic cancer who do not progress following systemic
therapy. Early phase II trials using extreme hypofractionation schedules
demonstrated an improved local control at the expense of substantial
gastrointestinal toxicity associated with reduced overall survival (OS). As a
result, further studies of fractionated SBRT with lower single fraction dose have
been proved to be less toxic and, when integrated with chemotherapy, to lead even
in improved OS. De Geus et al (Cancer, 2017) in one of the largest retrospective
studies, including 14,331 patients from the National Cancer Data Base, showed
that SBRT following chemotherapy in unresectable pancreatic adenocarcinomas improved
OS compared to chemotherapy alone or compared to the addition of external beam
radiotherapy or intensity modulated radiotherapy to chemotherapy.
The next
question that needs to be addressed is at what dose can we achieve the maximum
disease control with minimum toxicity. There is still no consensus on this as
there are no randomised trials available. Among the published data there is
great variability on the total dose prescribed, the dose per fraction as well
as the prescription isodose. A frequently reported dose is 40 Gy in 5 fractions
(BED10 72 Gy, BED3 147 Gy) while doses of 3 fractions (total
dose 30 – 45 Gy) and 5 fractions (total dose 25 -45 Gy) have also been described.
Another key
element in the successful treatment of pancreatic cancers with SBRT is the
management of the motion. Insertion of at least three fiducial markers usually
endoscopically is often implemented while biliary stents are controversial surrogates
for tumour position. A 4-dimensional computed tomography (4DCT) scan is
mandatory for all patients while contrast enhanced end-expiratory breath hold scans
are also recommended in order to define an internal target volume (ITV) and gastrointestinal
structure planning organ-at-risk volume (PRV). There is also the option to
treat during free breathing and in that case appropriate compensation such as
gating, tracking, compression, or a combination is recommended and according to
tumour or fiducial movement on respiration amplitude-reducing methods are appropriate.
Despite the limited
consensus on SBRT of pancreatic adenocarcinomas, it is widely agreed that this
treatment should be offered in high volume centres in order to achieve the best
possible outcomes. The Mobility / Technology Transfer Grant of ESTRO allowed me
to undertake a visit at the Erasmus MC Cancer Institute to observe this
treatment at all the stages; from simulation to planning and execution. This
knowledge has proved extremely valuable to our expanding department in a
University hospital that is also a tertiary centre for hepatobiliary cancers.