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Letter to the Editor
Clinical evidence that more precisely defined dose distributions will
improve cancer survival and decrease morbidity
!Received 6 March 2003; accepted for publication 7 March 2003"
#DOI: 10.1118/1.1570371$
To the Editor,
In a recent letter, Dr. Schulz and Dr. Kagan discuss their
pessimistic view that ‘‘More precisely defined dose distributions are unlikely to affect cancer mortality.’’ 1 They introduce the idea of the ‘‘Infinitron,’’ a hypothetical radiation
source than can create arbitrary dose distributions within the
body. They state that the Infinitron might result in fewer
complications, but improvements in survival for the average
cancer patient are likely to be imperceptible. They give several supporting arguments, including !a" a perfect radiation
source approximates surgery, !b" the dearth of diseasespecific survival data, and !c" the rising cost of unproven
technologies. We wish to address each of these points separately.
!a" A perfect radiation source approximates surgery. In
some cases curative cancer surgical procedures, such as the
Whipple procedure for pancreatic cancer resection, carry
substantial risk of operative and post-operative morbidity
and even mortality including post-operative infections and
complications of anesthesia. Many tumors are surgically inaccessible or technically unresectable, or if resectable carry a
high risk of collateral damage to surrounding organ systems.
Furthermore, a significant fraction of patients referred for
definitive radiation therapy, particularly for lung cancer, are
medically inoperable due to co-morbid conditions such as
compromised cardiac/lung function or obesity. Radiation can
succeed where surgery cannot.
The perfect radiation source might compete successfully
with surgery in many sites. Apart from the associated morbidity described above for surgery, radiation therapy can utilize the differential repair capabilities to kill tumor cells embedded within normal tissue while leaving the normal tissue
viable. In surgery, the tumor as well as normal tissue is removed. Furthermore, surgery cannot remove all of the clonogenic cells. The Infinitron and even currently available
treatment delivery technology, is a less invasive option to
surgery for treating microscopic disease extension or surrounding regional lymphatics which are at risk for tumor
recurrence. For example, post-surgery radiation therapy for
early stage breast cancer has proven to reduce cancer recurrence over surgery alone, even for patients with negative
surgical margins.2–5
!b" The dearth of disease-specific survival data. Though it
may be true that no randomized clinical trials showing the
benefits of IMRT or proton therapy have yet been reported,
nevertheless many clinical studies have described the dose
response for both normal tissue and tumors. We will use lung
cancer as an example. Several studies have shown a survival
advantage for higher dose levels.6 –11 Martel et al.8 estimate
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Med. Phys. 30 „6…, June 2003
from their data that to achieve 50% local progression-free
survival at 30 months 85 Gy will be required; this dose level
is considerably higher than that used routinely in clinics due
to the risk of lung complications. These lung complications
have been shown to be correlated with mean lung dose !or
similar surrogate, such as V 20). 12–17 Thus, there is clinical
evidence that technologies which allow increased dose to the
tumor while sparing healthy tissue will improve the balance
between complications and cure. For lung cancer, the Infinitron !or at least its current closest approximations" is exactly
what is needed to increase the poor 15% 5-year survival
#Cancer Facts and Figures 2003, American Cancer Soci
ety, !http://www.cancer.org/downloads/STT/CAFF2003PW
Secured.pdf"$ for lung cancer sufferers.
!c" The cost of unproven technologies. Any ‘‘new’’ technology is likely to be more expensive than the currently
available mass-produced devices to which it is compared, at
least initially. However, given the capabilities of modern engineering design and manufacturing, such new devices may
not always be more expensive, especially if their market
grows as they replace older generation systems. Let physicists and physicians investigate high risk/high return research, and leave it to the engineers to transfer the successful
scientific innovations into practical, useful and economical
devices. We agree with Schulz and Kagan that the ultimate
proof of any new technology is through randomized clinical
trials. However, this should not discourage researchers from
performing and publishing treatment planning studies
!thought experiments" to estimate the potential clinical significance of devices, such as magnetic dose focusing units,
before they are made. In fact, these treatment planning studies provide some data that is necessary to perform such costbenefit analyses.
In summary, we applaud and support those researchers
working in the areas of magnetic dose focusing, advanced
image-guided therapy, molecular imaging, Monte Carlobased dose calculation, IMRT, respiratory gating/breathhold/4D methods, proton therapy, etc. Though the Infinitron
does not yet exist, all of the aforementioned research efforts
are bringing us closer to this goal.
1
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2
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3
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0094-2405Õ2003Õ30„6…Õ1281Õ2Õ$20.00
© 2003 Am. Assoc. Phys. Med.
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P. J. Keall and J. F. Williamson: Letters to the Editor
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6
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7
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8
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9
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11
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13
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16
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!2002".
Paul J. Keall and Jeffrey F. Williamson
Department of Radiation Oncology,
Virginia Commonwealth University,
Richmond, Virginia 23298