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isolated from blood drawns harvested before the
administration of the first fractioned dose of RT and 24 h
later. 4. Statistical analysis: Anova test is performed to
analyse the differential expression across IRS classes and
a Spearman analysis is performed to assess correlation
between expression and IRS index.
Results
The expression of
DDB2, GADD45A, CDKN1A,
and
ATM
genes following irradiation
2,3
has been correlated with the
in vitro
IRS evaluated by the G2-chromosomal assay; at
present, a positive correlation between
ATM
expression
and IRS could be inferred despite the unavoidable inter-
individual variability. The analyses on other DDR genes are
in progress.
Conclusion
The innovation of this study is the use of a molecular
biology approach to assess patient radiosensitivity before
RT, in the frame of an integrated approach between
clinicians and biologists.
References
1. Pantelias GE. & Terzoudi G. I.
Radiother. Oncol.
101
(2011).
2. Mognato M. & Celotti L.
Mutat. Res. Mol. Mech.
Mutagen.
578
(2005).
3. Girardi C.
et al.
PLoS One
7
(2012).
Poster: Radiobiology track: Radiobiology of lung cancer
PO-0975 Clinical utilization of the radiation-hypoxia-
induced abscopal/bystander effect in lung cancer
S. Tubin
1,2
, S. Gupta
3
, A.M. Mansoor
4
1
KABEG Klinikum Klagenfurt, Radioonkologie, Klagenfurt,
Austria
2
Sylvester Comprehensive Cancer Center- University of
Miami Leonard Miller School of Medicine, Department of
Radiation Oncology, Miami, USA
3
Georgia Cancer Center- Augusta University- Augusta-
GA- USA, Health Sciences, Augusta, USA
4
National Cancer Institute- National Institutes of Health,
Radiotherapy Development Branch- Radiation Research
Program- Division of Cancer Treatment and Diagnosis,
Rockville, USA
Purpose or Objective
To report on initial results in a small series of consecutive
patients treated with high-dose hypofractioneted
radiotherapy (1-3 fractions) in the treatment of
oligometastatic patients with large tumor masses focusing
on application of results previously obtained by in vitro
studies on radiation-induced abscopal/bystander effect.
Our previous study (unpublished data) focused on
targeting tumor hypoxia that induced a strong
abscopal/bystander effect. We provide data that support
the contention that high-dose radiation to the part of a
large gross tumor volume (GTV) has the potency to induce
a robust bystander effect, as well as abscopal (distant)
effects.
Material and Methods
In the in vitro studies conditioned medium-transfer
experiments with A-549, H-460 lung cancer cells, as well
as their hypoxic clones (A-549HR, H-460HR), were
performed. All the cells were irradiated in normoxic or
hypoxic conditions with 10Gy single dose and cell growth
and survival were monitored by real time cell electronic
sensing (RTCES) System and colony forming assay,
respectively. In the clinical study, 5 consecutive
oligometastatic patients with large hypoxic cancers of
lung (3), neck (1) and mediastinum (1) were treated with
high dose radiotherapy using high-energy photons. All
lesions were irradiated partially by targeting the central
hypoxic region (Figure 1), which corresponded to 30% of
total GTV (Mean GTV volume 181 cc, mean diameter 6, 8
cm) with 10Gy single fraction prescribed to the 70%
isodose line (Dmax 14 Gy). No patient got
chemotherapy/immune therapy.
Results
10Gy- in vitro induced abscopal effect in hypoxic
conditions was very effective in inducing growth delay of
both, unirradiated normoxic and hypoxic lung cancer cells
(Table 1), so we moved forward with clinical application
of bystander/abscopal effect. In all the treated patients,
a significant bystander effect after mean time of 3 weeks
and in 1 of the patients significant abscopal effect was
also observed (Figure 2). Overall response rates for
symptom relief and mass response were 100% (1 complete
and 4 good partial response).No patient experienced acute
or late toxicity of any grade.
Conclusion
Considering
the clinical benefit/toxicity ratio, the clinical
exploitation
of
biological
properties
of
bystander/abscopal effect induced by partial irradiation
of large tumor masses, and almost any dose distribution to
the normal tissue outside the irradiated tumor, could
make bystander/abscopal effect at least more effective
than conventional radiation therapy for treatment of
advanced cancers and the perfect treatment option for
symptomatic patient. Further, by inducing the distal
responses, like in the case of one of the patients,