Page 303 - 2014 Printable Abstract Book
P. 303
a robust up-regulation of EDA2R a member of the TNFR superfamily mediating anoikis in jejunum, ileum
and colon from day 4 to day 12. Conclusions: The activation of TNF mediated matrix proteases and anoikis
signaling could contribute intestinal mucosal shedding and epithelial barrier breakdown at early time
points after TBI.
(PS5-28) Radiation-induced inflammatory plasma cytokines are associated with lung toxicity in patients
with non-small cell lung cancer. Shankar Siva; Michael MacManus; Tomas Kron; Nickala Best; Jai Smith;
Pavel Lobachevsky; David Ball; and Olga Martin, Peter MacCallum Cancer Centre, East Melbourne,
Australia
Purpose: Lung inflammation leading to severe pulmonary toxicity can occur in patients receiving
radiotherapy (RT) for non-small cell lung cancer (NSCLC). We investigated the kinetics and clinical
correlates of RT-induced inflammatory cytokine concentrations in serial blood samples in patients treated
with curative-intent RT. Our hypothesis was that one or a combination of cytokines could be prognostic
for clinical lung toxicity. Experimental Design: This was a translational substudy of an independent ethics
board approved prospective clinical trial. Twelve patients with NSCLC received definitive RT to 60 Gy in
6weeks. Six of these received concurrent platinum based chemotherapy (ChemoRT group). Blood samples
st
were drawn and plasma separated before therapy, at 1 and 24 hours after the 1 fraction, 4 weeks into
RT, and 12 weeks after completion of treatment. These were analysed using an ELISA based multiplex
assay of 22 inflammatory cytokines. Results: Of 12 cytokines found in concentrations above the limit of
detection, 10 demonstrated significant temporal changes in plasma concentration across sampled
timepoints. For Eotaxin, IL-33, IL-6, MDC, MIP-1a and VEGF this was dependent upon treatment group
(ChemoRT vs RT, p < 0.010), whilst expression of IP-10, MCP-1, MCP-3, MIP-1, TIMP-1 and TNF- was not.
A correlation between mean lung radiation dose delivered and a reduction in cytokine concentration was
2
2
2
found at 1 hour for IP-10 (r = 0.858, p < 0.001), MCP-1 (r = 0.653, p = 0.003), MCP-3 (r = 0.721, p = 0.002)
2
and IL-6 (r = 0.531, p = 0.017). In patients with severe pulmonary toxicity there were significant
differences in Eotaxin, IL-6 and TIMP-1 concentration at 24 hours, as well as in IP-10 and MCP-1 at 1 hour
(all p-values < 0.050) compared to baseline. Conclusions: Inflammatory cytokine concentrations changed
during and after RT. Early inducible changes in IP-10, MCP-1, MCP-3 and IL-6 correlated with mean lung
dose. Changes in IP-10, MCP-1, Il-6, Eotaxin, and TIMP-1 were associated with severe toxicity. Early
changes in inducible cytokines during to RT, several not previously documented, could help predict lung
toxicity and lead to new therapeutic strategies.
(PS5-29) A novel technique for high-throughput, high-precision spatial mapping of the biologic
1
1
1
1
effectiveness of therapeutic proton beams. Fada Guan ; Lawrence Bronk ; Matthew D. Kerr ; Uwe Titt ;
1
2
1
2
1
1
Steven H. Lin ; Dragan Mirkovic ; Ronald X. Zhu ; Mary Sobieski ; Clifford Stephan ; Radhe Mohan ; and
1
1
David R. Grosshans , UT MD Anderson Cancer Center, Houston, TX and Texas A&M Health Science Center,
Houston, TX
2
Background: The physical properties of protons have been well characterized and their dose
distributions are superior to traditional photon therapy. Unlike photons, the linear energy transfer (LET)
and hence biologic effectiveness of proton beams varies along the beam path. The selective placement of
areas of high effectiveness could enhance tumor cell kill and simultaneously spare normal tissues.
301 | P a g e
and colon from day 4 to day 12. Conclusions: The activation of TNF mediated matrix proteases and anoikis
signaling could contribute intestinal mucosal shedding and epithelial barrier breakdown at early time
points after TBI.
(PS5-28) Radiation-induced inflammatory plasma cytokines are associated with lung toxicity in patients
with non-small cell lung cancer. Shankar Siva; Michael MacManus; Tomas Kron; Nickala Best; Jai Smith;
Pavel Lobachevsky; David Ball; and Olga Martin, Peter MacCallum Cancer Centre, East Melbourne,
Australia
Purpose: Lung inflammation leading to severe pulmonary toxicity can occur in patients receiving
radiotherapy (RT) for non-small cell lung cancer (NSCLC). We investigated the kinetics and clinical
correlates of RT-induced inflammatory cytokine concentrations in serial blood samples in patients treated
with curative-intent RT. Our hypothesis was that one or a combination of cytokines could be prognostic
for clinical lung toxicity. Experimental Design: This was a translational substudy of an independent ethics
board approved prospective clinical trial. Twelve patients with NSCLC received definitive RT to 60 Gy in
6weeks. Six of these received concurrent platinum based chemotherapy (ChemoRT group). Blood samples
st
were drawn and plasma separated before therapy, at 1 and 24 hours after the 1 fraction, 4 weeks into
RT, and 12 weeks after completion of treatment. These were analysed using an ELISA based multiplex
assay of 22 inflammatory cytokines. Results: Of 12 cytokines found in concentrations above the limit of
detection, 10 demonstrated significant temporal changes in plasma concentration across sampled
timepoints. For Eotaxin, IL-33, IL-6, MDC, MIP-1a and VEGF this was dependent upon treatment group
(ChemoRT vs RT, p < 0.010), whilst expression of IP-10, MCP-1, MCP-3, MIP-1, TIMP-1 and TNF- was not.
A correlation between mean lung radiation dose delivered and a reduction in cytokine concentration was
2
2
2
found at 1 hour for IP-10 (r = 0.858, p < 0.001), MCP-1 (r = 0.653, p = 0.003), MCP-3 (r = 0.721, p = 0.002)
2
and IL-6 (r = 0.531, p = 0.017). In patients with severe pulmonary toxicity there were significant
differences in Eotaxin, IL-6 and TIMP-1 concentration at 24 hours, as well as in IP-10 and MCP-1 at 1 hour
(all p-values < 0.050) compared to baseline. Conclusions: Inflammatory cytokine concentrations changed
during and after RT. Early inducible changes in IP-10, MCP-1, MCP-3 and IL-6 correlated with mean lung
dose. Changes in IP-10, MCP-1, Il-6, Eotaxin, and TIMP-1 were associated with severe toxicity. Early
changes in inducible cytokines during to RT, several not previously documented, could help predict lung
toxicity and lead to new therapeutic strategies.
(PS5-29) A novel technique for high-throughput, high-precision spatial mapping of the biologic
1
1
1
1
effectiveness of therapeutic proton beams. Fada Guan ; Lawrence Bronk ; Matthew D. Kerr ; Uwe Titt ;
1
2
1
2
1
1
Steven H. Lin ; Dragan Mirkovic ; Ronald X. Zhu ; Mary Sobieski ; Clifford Stephan ; Radhe Mohan ; and
1
1
David R. Grosshans , UT MD Anderson Cancer Center, Houston, TX and Texas A&M Health Science Center,
Houston, TX
2
Background: The physical properties of protons have been well characterized and their dose
distributions are superior to traditional photon therapy. Unlike photons, the linear energy transfer (LET)
and hence biologic effectiveness of proton beams varies along the beam path. The selective placement of
areas of high effectiveness could enhance tumor cell kill and simultaneously spare normal tissues.
301 | P a g e
