Philadelphia Medicine Summer 2018 - 19

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n my relatively short career as a radiation
oncologist, the field of radiation oncology
has evolved considerably. In 2007, while
I was a resident at Fox Chase Cancer Center,
I attended a conference hosted by Fox Chase
called "Hypofractionation, a Shortcut to the
Future." Hypofractionation is a technique of
delivering higher doses of radiation per day over
fewer days than conventional radiation, and
was being used only sporadically at that time
as its safety and efficacy were largely unproven.
I remember many heated debates at this
conference among thoughtful leaders in the
field of radiation oncology regarding all of the
issues surrounding this novel approach. There
were a lot of skeptics, as hypofractionation was
a broad departure from standard radiation
techniques where lower doses of radiation are
delivered over several weeks.

increase the risk of late effects. Late effects can
occur many, many years after radiation.
Thus, patients need to be followed for a long
time to detect these effects. One way to mitigate
normal tissue toxicity is to use very small
margins of error around the tumor. However,
this requires improved target delineation and,
for tumors that move with respiration, a means
of tracking the tumor in real time. There are
many radiation machines on the market that
can do this, however, one that is particularly well
suited for real time tracking is the CyberKnife.

Conventional radiation has a long track record of being safe
with a generally low risk of damage to normal, healthy tissues.
However, for some cancers, it is not that effective. Thus, the idea of
hypofractionation came about. This made sense from a theoretical
standpoint, but practically speaking, how could one deliver these high
doses of radiation safely? The short answer was, better technology.
With improvements in technology, new radiation machines
began to be developed that had better ways of imaging tumors
and focusing radiation more precisely on the target while sparing
the adjacent normal tissues. This allowed radiation oncologists to
deliver radiation more accurately and prescribe higher doses which
meant improvements in tumor response and ultimately cure while
at the same time not increasing the risk of collateral damage to the
adjacent normal tissues.
This is the holy grail of radiation oncology! Phase I and II clinical
trials were being conducted to determine which cancers were best
suited to hypofractionation and what doses and fractionation schemes
provided the best results. Early stage lung cancer was one of the sites
for which this technique was employed early on, primarily because
high radiation doses are necessary to ablate lung cancer cells, and
the normal lung tissue is exquisitely sensitive to radiation.
Prostate cancer is another cancer for which hypofractionation
has been found to be very useful. Based on the biology of prostate
cancer, higher radiation doses per fraction induce better cell death
than lower radiation doses. The concern when delivering higher doses
of radiation per fraction is what will be the effects on the normal
tissues? Radiobiology principles tell us that higher doses per fraction

The CyberKnife is essentially a linear accelerator mounted on a
robotic arm with a sophisticated imaging system that allows for real
time tumor tracking during treatment delivery. For tumors that
move with respiration, this is very useful, as one can decrease the
margin of error around the tumor, thereby minimizing the dose to
the surrounding normal tissues and allowing for higher doses to be
delivered to the target.
The ultimate effect is that one is able to improve the therapeutic
index, meaning better tumor control with less toxicity. The concept
of delivering very high doses of radiation in few fractions using a
coordinated system to identify the target ("stereotaxis") was developed
by a Swedish neurosurgeon, Dr. Lars Leksell, in 1951. The first
machine to accomplish this was the Gamma Knife which was first
used in 1967 to treat a craniopharyngioma. The Gamma Knife is
composed of 211 well collimated beams from Cobalt 60 sources,
distributed around a half-spherical collimator helmet, allowing a
circumscribed focus of beams to be produced in the central part of
the patient's skull.
Continued on page 20

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