Editorial
Hypo Fractionated Radiotherapy in Prostate Cancer
Georgios Plataniotis*
Department of Clinical Oncology, Brighton and Sussex University Hospitals, UK
*Corresponding author: Georgios Plataniotis, Department of Clinical Oncology, Brighton and Sussex University Hospitals, UK
Published: 13 Feb, 2017
Cite this article as: Plataniotis G. Hypo Fractionated
Radiotherapy in Prostate Cancer. Clin
Oncol. 2017; 2: 1201.
Editorial
External beam Radiation Therapy (RT) is given in many small fractions (fractionated RT)
usually 20-40 with a dose per fraction of 1.8-2 Gy, because it is known that cell-killing is much less
compared to a single-dose or few large doses [1-3]. Fractionation spares some of the radiationinduced
damage of the normal tissues--surrounding the area of the tumour--which they can recover
from, while neoplastic tissues will not, resulting in the cure of cancer with radiotherapy.
The macroscopic and clinical effects of fractionation on neoplastic and normal tissues can be
measured with the iso-effective Linear-Quadratic formulation [1-4] which calculates the Biologically
Effective Dose of fractionated RT schedules. The basic tissue-related parameter in this formula is the
α/β ratio which characterizes each type of tissue [4,5].
Tumours and late-responding normal tissues respond differently in variable RT dose
fractionations because of the larger proportion of cycling cells in tumors. Late reacting normal
tissues have a lower α/β ratio (2-5 Gy) and therefore a higher fractionation sensitivity compared to
the early-reacting normal tissues and most of the tumors (α/β = 8-15 Gy).
The last ones have a high fractionation sensitivity as an increase in the dose per fraction (for a
given total dose) causes more cell-kill to them, compared to the cell-kill an equal increase of dose
per fraction (for the same total dose) causes to tissues characterized by a high α/β ratio [6] (the interested reader can look at references 1 and 2 and they can also do their own simple calculations
using clinical examples).
Prostate tumors contain smaller (than the other cancers)fractions of cycling cells, so after an
analysis of the clinical RT data and dose-response relationships, various authors suggested that
prostate tumors might not respond to changes in fractionation similarly to other cancers. They
are characterized by low α/β ratios and therefore have high-fractionation sensitivity. For prostate
cancer α/β ratio has been calculated at 1.5 Gy [7-11] and more recently based on data of modern
clinical studies at 1.3 Gy or higher at 1.8 Gy in the CHHIP trial [12-15].
Consequently there is a therapeutic benefit expected if they were treated with fewer and larger
fractions—a technique called hypo fractionated RT [6] -- where doses per fraction of 2.5-3.5 Gy are employed. With the recent advancements of technical capacity in RT and the excellent localization,
treatment planning and dose delivery techniques (IMRT, IGRT, Tomotherapy) it has been possible
to make hypo fractionation feasible and safe (in terms of normal tissue sparing) especially in prostate
cancer patients.
The relevant, with the prostate, late-responding normal tissue is the rectum and there is some
evidence that α/β ratio of the rectumis around 4 Gy, i.e. higher than for most other late sequelae
[16]. As Brenner [7] has noted this would result in increased tumor control for a given level of late
complications, or decreased late complications for a given level of tumor control i.e. an increase of
therapeutic ratio.
However hypo fractionation for prostate Ca is not an entirely novel treatment approach.
Satisfactory outcomes have been reported 22 years’ experience (1962–1984) with 232 prostate cancer
patients treated with 6-fractions of 6 Gy each with the much inferior dose distributions of that age
(compared to the current ones) [17]. There is also extensive experience from the Manchester “hypo fractionation school” of treating prostate cancer with a 15 x 3.1 Gy (total 46.5 Gy) [18].
In the last couple of years, randomized studies (Table 1) comparing standard with hypo
fractionated RT schedules in more than 6,000 patients—mainly of low and intermediate-risk—have
reported that hypo fractionated RT is working at least equally well with standard fractionation.
Of note is that the effect of hypo fractionation remained regardless of the use of hormonotherapy.
The urinary and gastrointestinal reactions were comparable and the interested reader should refer to the original publications [12-15] taking into account the possible
differences in RT techniques.
The simultaneous integrated boost technique used in the Intensity
Modulated RT (IMRT) involves a dose gradient across the (three in
most techniques) Planning Target Volumes (PTVs), and reduces the
dose and the dose per fraction by identical proportions and therefore
is not expected to be affecting the observed hypo fractionation effect [19].
Following the reported and gained experience it is felt that
hypo fractionated RT for the low and intermediate-risk prostate Ca
patients can become a standard of care [20], provided that advanced
RT techniques are used. This will increase patients’ convenience and
turnover in RT departments [20].
Table 1
References
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