Page 204 - 2014 Printable Abstract Book
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with partial tumor response in the unirradiated lung. An increase in cytotoxic T cells was observed in both
irradiated and unirradiated lungs after radiation and checkpoint blockade. This preclinical study provides
evidence to support combination trials with RT and checkpoint blockade.
(PS3-25) Simulations of SABR using the individual cell model, HYP-RT. Do we need to deliver extra dose
to hypoxic tumors that cannot reoxygenate? Wendy M. Harriss-Phillips and Eva Bezak
Royal Adelaide Hospital, Adelaide, South Australia, Australia
Purpose: Stereotactic ablative radiation therapy (SABR) is becoming an increasingly important
treatment modality to deliver large localized radiation doses for primary as well as oligometastatic disease
sites, for cancers such as HNSCC. Non-conventional dose fractionation effects are still a subject of
radiobiological research; including issues such as non-linear-quadratic dose response and reduction of
beneficial reoxygenation effects. To compare cell kill dynamics of conventional radiotherapy with SABR,
an established stochastic tumor growth and radiotherapy model has been utilized to compare oxic and
8
hypoxic tumor response to extreme hypofractionation. Methods: Virtual tumors consisting of 10 cells
and realistic pO2 profiles received doses of 6, 9, 12 and 15 Gy/# (2-3 fractions/week), with and without
volume dependent tumor reoxygenation. Linear-quadratic-cubic (LQC) response was modelled using
-1
cubic coefficient, γ = β/3DL, to calculate cell survival probabilities (DL = 10 or 18 Gy, α = 0.3 Gy , β = 0.03
Gy ). Oxygenation enhancement ratios of 1-3 were based on pO2, while phase dependent radiosensitivity
-2
and cell kinetics were based on HNSCC. Results: Tumor control doses for 2 Gy/# RT were consistent with
clinical doses of 73±4 Gy for oxic tumors. Hypoxic tumors an extra required 13 Gy, in spite of
reoxygenation, while 30 Gy extra was required with no reoxygenation modelled. SABR tumor control EQD2
ranged from 66-94 Gy and 104-128 Gy for oxic vs. hypoxic tumors, corresponding to +1 (15Gy/#), +1
(12Gy/#), +3 (9Gy/#) or +5 (6Gy/#) fractions (±1). 12-15 Gy/# was potent enough to ignore reoxygenation,
while reoxygenation reduced outcomes by 1-2 fractions for 6 and 9 Gy/#. LQC vs. LQ differences were only
observed for oxic tumors, with LQC requiring an extra fraction for 50% of simulations. Altering DL from 18
to 10 Gy had an additional +1 fraction impact. Summary: The HYP-RT model of individual cell proliferation
predicted SABR hypoxic tumor control doses (EQD2) of 104-128 Gy for four ablative dose schedules, which
were 30-40 Gy higher than for oxic tumors. Reoxygenation effects were not significant above 12 Gy/#.
Impending simulations will consider effects such as immediate versus delayed accelerated cellular
repopulation and alternate cell kinetic/response parameters applicable to NSCLC.
(PS3-26) Modeling Radiobiological Effects induced by proton therapy. Reza Taleei, PhD; Uwe Titt, PhD;
Christopher R. Peeler, PhD Candidate; and Radhe Mohan, The University of Texas, MD Anderson Cancer
Center, Houston, TX
The physics of proton therapy has been well characterized, however the radiobiological effects of
proton therapy have not been fully elucidated. A mechanistic model for cell survival which can incorporate
all the biological events including; initial damage to the cell, subsequent DNA repair and signaling, as well
as cell death and other biological consequences such as mutation is still missing. The field of radiation
biology has progressed over the last three decades and advanced our knowledge of DNA repair, cell
signaling, chromosome aberrations and cell survival responses to radiation. This offers an opportunity to
propose mechanistic models for the series of biological events which arise in response to radiation
202 | P a g e
irradiated and unirradiated lungs after radiation and checkpoint blockade. This preclinical study provides
evidence to support combination trials with RT and checkpoint blockade.
(PS3-25) Simulations of SABR using the individual cell model, HYP-RT. Do we need to deliver extra dose
to hypoxic tumors that cannot reoxygenate? Wendy M. Harriss-Phillips and Eva Bezak
Royal Adelaide Hospital, Adelaide, South Australia, Australia
Purpose: Stereotactic ablative radiation therapy (SABR) is becoming an increasingly important
treatment modality to deliver large localized radiation doses for primary as well as oligometastatic disease
sites, for cancers such as HNSCC. Non-conventional dose fractionation effects are still a subject of
radiobiological research; including issues such as non-linear-quadratic dose response and reduction of
beneficial reoxygenation effects. To compare cell kill dynamics of conventional radiotherapy with SABR,
an established stochastic tumor growth and radiotherapy model has been utilized to compare oxic and
8
hypoxic tumor response to extreme hypofractionation. Methods: Virtual tumors consisting of 10 cells
and realistic pO2 profiles received doses of 6, 9, 12 and 15 Gy/# (2-3 fractions/week), with and without
volume dependent tumor reoxygenation. Linear-quadratic-cubic (LQC) response was modelled using
-1
cubic coefficient, γ = β/3DL, to calculate cell survival probabilities (DL = 10 or 18 Gy, α = 0.3 Gy , β = 0.03
Gy ). Oxygenation enhancement ratios of 1-3 were based on pO2, while phase dependent radiosensitivity
-2
and cell kinetics were based on HNSCC. Results: Tumor control doses for 2 Gy/# RT were consistent with
clinical doses of 73±4 Gy for oxic tumors. Hypoxic tumors an extra required 13 Gy, in spite of
reoxygenation, while 30 Gy extra was required with no reoxygenation modelled. SABR tumor control EQD2
ranged from 66-94 Gy and 104-128 Gy for oxic vs. hypoxic tumors, corresponding to +1 (15Gy/#), +1
(12Gy/#), +3 (9Gy/#) or +5 (6Gy/#) fractions (±1). 12-15 Gy/# was potent enough to ignore reoxygenation,
while reoxygenation reduced outcomes by 1-2 fractions for 6 and 9 Gy/#. LQC vs. LQ differences were only
observed for oxic tumors, with LQC requiring an extra fraction for 50% of simulations. Altering DL from 18
to 10 Gy had an additional +1 fraction impact. Summary: The HYP-RT model of individual cell proliferation
predicted SABR hypoxic tumor control doses (EQD2) of 104-128 Gy for four ablative dose schedules, which
were 30-40 Gy higher than for oxic tumors. Reoxygenation effects were not significant above 12 Gy/#.
Impending simulations will consider effects such as immediate versus delayed accelerated cellular
repopulation and alternate cell kinetic/response parameters applicable to NSCLC.
(PS3-26) Modeling Radiobiological Effects induced by proton therapy. Reza Taleei, PhD; Uwe Titt, PhD;
Christopher R. Peeler, PhD Candidate; and Radhe Mohan, The University of Texas, MD Anderson Cancer
Center, Houston, TX
The physics of proton therapy has been well characterized, however the radiobiological effects of
proton therapy have not been fully elucidated. A mechanistic model for cell survival which can incorporate
all the biological events including; initial damage to the cell, subsequent DNA repair and signaling, as well
as cell death and other biological consequences such as mutation is still missing. The field of radiation
biology has progressed over the last three decades and advanced our knowledge of DNA repair, cell
signaling, chromosome aberrations and cell survival responses to radiation. This offers an opportunity to
propose mechanistic models for the series of biological events which arise in response to radiation
202 | P a g e
