Blueberry

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Dose rate effects on tumor cell response to
intensity modulated fractionated radiation therapy
ASTRO 2005 Denver
Harald Paganetti Massachusetts General
Hospital Harvard Medical School Boston, MA 02114
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Motivation

• Complex treatment techniques (IMRT, IMPT)
  require longer dose delivery times (decrease in
  dose rate)
• Dose-rate effects in IM treatments can be
  expected to make cell killing more nonuniform
  over the target volume

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• Cell killing tends to decrease with increasing
  fraction delivery time because of sublethal
  damage repair
• When fraction delivery times are comparable to
  or longer than the half-time for repair,
  decreases in cell killing may significantly
  reduce overall treatment effectiveness

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Methods and Materials

• Linear quadratic model
• phenomenological dose rate parameter
• More mechanistic radiobiological models
• based on repair kinetics
• dose rate effects considered naturally

ASTRO 2005 Denver
Lethal / Potentially Lethal (LPL) Curtis
Lethal and Potentially Lethal Lesions Induced by
Radiation -A Unified Repair Model. Radiat Res
1986 106 252-270
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Results I
I. Cell survival for different dose rates
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PLL (solid line) and LL (dashed line) for HX118
Potentially Lethal Lesions (PLL) and Lethal
Lesions (LL) during irradiation with 2Gy/min
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Cell survival as a function of dose delivered
with 2 Gy/min and after infinite repair time.
For RT112, cell survival for 2 Gy/min after
different times post irradiation based on lethal
lesions only.
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Potentially lethal lesions (short-dashed line),
lethal lesions (long-dashed line) and total
number of lesions (solid line) after a 2 Gy
irradiation of RT112
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After irradiation
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2 Gy fraction delivered in 30 min ( 0.07 Gy/min)
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Results II
II. Cell survival for different dose rates for
fractionated irradiation

• 60 Gy in 30 fractions
• Each irradiation (except for the first fraction)
  starts with a number of LLs and PLLs remaining
  from the previous fraction
• Time for repair is set to 24 hours after each
  irradiation and 72 hours every 5 fractions
• After 30 fractions, there is infinite time for
  repair (t?8)

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Cell Survival (for 9 endpoints) for different
dose rates Lower figures detailed view on the
first 5 fractions All PLLs present at a given
time after irradiation are assumed to be lethal
to illustrate repair effects
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For dose delivery with lt 2 Gy/min (prolonged
delivery) additional dose has to be delivered to
achieve the same effect as with a 2 Gy/min
treatment !
10 decrease in equivalent dose can result in a
reduction in tumor control probability in the
order of 20
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Conclusions

• For the considered endpoints, 2 Gy delivered in
  30 min reduces the equivalent dose between 1.3
  and 12 compared to 2 Gy delivered in 1 min
• A manuscript describing this study is currently
  in press in
• International Journal of Radiation Oncology,
  Biology, Physics
• Paganetti H Changes in tumor cell response due
  to prolonged delivery times in fractionated
  radiation therapy.

ASTRO 2005 Denver