Low Dose Radiationin Medical Interventions(Radiation Oncology Experience)
Tomoaki Tamaki
Department of Radiation Oncology

Basic assumption of radiation
exposures for medical purposes• “With regard to medical exposure of patients, it is not
appropriate to apply dose limits or dose constraints,
because such limits would often do more harm than
good. Often, there are concurrent chronic, severe, oreven life-threatening medical conditions that are morecritical than the radiation exposure. …”(ICRP, 2007. Radiological Protection in Medicine. ICRP Publication 105. Ann. ICRP 37 (6).)• It is important to understand that medical exposure isfundamentally different from exposure to the public.
• But, with that said, …

Data on the Applicationof Radiation in Medicine• In the month of September, 2011,
CT>2,000,000 patients*
PET, PET/CT>48,000 patients*
Radiotherapy >20,000 patients*** Number of tests ** number of CT simulation

Population of Fukushima prefecture: ≈1,890,000 (2017)
How much radiation are these people (patients) receiving?

Radiotherapy• Radiation oncology professionals prescribes ionizing
radiation to treat cancer in the form of external beam
radiotherapy or brachytherapy.
• In curative treatment, it is our aim to cure the patientsand expect long-term survival.
• In Japan, about 200,000 patients/year receive
radiotherapy.
• The dose we prescribe is about 60 Gy to the malignantlesion.
• In most cases, radiotherapy is given in 2 Gy/fraction.

So, how much is the radiation
used for radiotherapy?
• Natural radiation ≈ 2 mSv/year• CT (diagnosis) ≈ 5-30 mSv/scan• Radiotherapy ≈ 2 Gy (Sv)/day (This is 2,000 mSv/day)→ This is about 1,000 years worth of natural radiation, per day.
(Average natural radiation in Japan = 2.1 mSv/year)“Millennium radiation/day”
In total, the dose is 60-70 Gy (Sv)/treatment.
(This is 30,000-35,000 years worth of natural radiation in total.)
What is “low dose” in radiotherapy? – Certainly, NOT in RT field.
So, how about the dose outside of the radiation field?

How much is out-of-field radiation?
Breast Cancer
Whole breast irradiation

Prostate Cancer
Prostate irradiation

2.2 mSv (Top of the head) 0.8 mSv
2 Gy(Sv)

1.3 mSv (Chest)

2.3 mSv (Pelvis)

2 Gy(Sv)

30-70 mSv
In this presentation,“low dose” is definedin totalas the dose outside of the radiation field.

What is the effect of low dose?
(out-of-field dose)• There are no acute symptoms which raise concerns
for radiation oncologists in a regular clinic.
• The only concern may be the risk of second cancers.
• HOWEVER, for clinicians, the risk of second cancers
in high-dose regions within the radiation fields tend
to be a much bigger concern (for logical reasons).
• How much is the risk of second cancers from the“low dose”?

Issues in the analysis ofsecond primary cancer (SPC)• The incidence of SPC is influenced by many factors• Radiation (in-field and out-of-field)• Other factors: age, genetic factors, environmentalfactors, etc.

• Often, “radiation induced” SPC is defined by thefollowing characteristics:• Diagnosed after a latency period (often ≥5 years)• Within the radiation field• Different histology from the original cancer• Not present at the time of radiotherapy

Issues in the analysis ofsecond primary cancer (SPC)• Who to compare with…

• General population vs. non-irradiated patients• The presence of bias (difference in surveillance,background risk factors, observed duration) requires
attention• Study Designs• Population-based study• Higher statistical power: large cohort• Limited information of possible risk factors (other thanradiation)• Institutional study• Lower statistical power: limited size
• Possible bias (selection, etc)
• Ability to analyze the effect of risk factors

Radiotherapy for breast cancer• For early stage breast cancer, the patients receive
breast conserving surgery and post-surgery wholebreast irradiation.
• The post-surgery radiotherapy reduces the risk ofrecurrence in breast to about 1/3.
• Recent development in surgery, radiotherapy, andchemo/hormonal therapy is improving the clinicaloutcomes of breast cancer treatment including
loco-regional control.

Radiotherapy for breast cancer

Risk of second primary cancer (meta-analysis)• Incidence of SPC in close proximity to radiation field (lung,esophagus, soft tissues and the thyroid regions) wereanalyzed.
• “... irradiated patients overall had a 23% higher risk of
second non-breast cancer compared with the general
female population. ...” (non-irradiated had a 8% higher risk)• “The above findings do not upset the benefit of radiation in
the loco-regional treatment of breast cancer, but it certainly
calls for awareness.”(Grantzau T, Overgaard J. Radiother Oncol 121:402-423, 2016)

Radiotherapy for breast cancer

Risk of second primary cancer (national population based study)
Radiotherapy-associated site vs. non-RT associated sites(high-dose region)(low-dose region)• The estimated attributable risk related toradiotherapy:• Radiotherapy-associated sites (high-dose region):→ 1 second cancer in every 200 women treated.
• Non-radiotherapy-associated sites (“low-dose” region):→ No increased risk.
(Grantzau T, et al. Radiother Oncol 106:42-49, 2013)

Subtotal RT-associated sites

HR 1.34 (1.11 – 1.61)

Subtotal non-RT-associated sites

HR 1.04 (0.94 – 1.16)(Grantzau T, et al. Radiother Oncol 106:42-49, 2013)

Prostate Cancer• Good clinical outcomes compared to other cancers
10-year relative survival rate – Overall 94.5%(Report from National Cancer Center Japan)• Stage I: 100%
• Stage II: 100%
• Stage III: 100%
• Stage IV: 40.5%• Multiple treatment options: Active surveillance,
hormonal therapy, surgery, and radiotherapy.
• Common radiotherapy today: Total of 70―80 Gy in
2 Gy/fraction using IMRT technique.

Radiotherapy for prostate cancer

Risk of second primary cancer (meta-analysis)• “Given the multiple factors involved, and heterogeneity amongstudies, it is very difficult to tease out definitive answers
regarding irradiation and the risk of SPCs.”• “Putting all the potential cofounders and biases aside, however, it
must be acknowledged that a small increased risk of SPC andRISPC (radiation-induced SPC) in irradiated prostate patients has
been observed in several studies.”• The risk of RISPC appears small: in the range of 1 in 220 to 1 in
290 over all durations of follow-up, based on older radiation
techniques.

(Murray L, et al. Radiother Oncol 110:213-228, 2014)

Radiotherapy for prostate cancer

Risk of second primary cancer (institutional study)• 2658 patients
Surgery (n=1348)
IMRT (n=897)
Brachy (n=413)• The 10-year SPC-free survival:• Surgery 89%, IMRT 83%, Brachy 87%(Surgery vs. IMRT, p = 0.002)• Overall, the incidence of SPC after IMRT or BT, both pelvic (highdose) and extrapelvic (low-dose), was not significantly different fromthat after surgery when adjusted for age and smoking history.
(Zelefsky MJ, et al. BJU International, 110:1696-1701, 2012)

List of priorities...
• Local Control (curability of treated region)• Acute toxicities (high dose region)• Disease control (recurrence)• Late toxicities (high dose region)...
• Second primary cancer (high dose region)
RT-independent >> RT-related• Second primary cancer (low dose region)
RT-independent >> RT-related

Summary• In the field of radiotherapy (radiation oncology), the magnitude
of out-of-field radiation dose can be in the range of 10-100
mSv.
• The effect of low dose radiation (≈mSv) do not usually receive
much attention compared to the high dose radiation (≈Sv(Gy))
in radiotherapy.
• A small increase in second primary cancer related to high dose
irradiation (often within irradiation fields) has been reported incancer patients receiving radiotherapy. Such an increase is not
significantly observed in low-dose region outside of theirradiation field, even in many of the population-based studies.
• The effect of radiation on the incidence of SPC should be
carefully analyzed in the view of other significant risk factors,