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evolution to current treatment intensity did not consider
HPV-related disease. The profiles of patients with HPV-
related OPC at risk of DM are now being better
understood. There is opportunity to modify approaches so
that intensive local treatment can be minimized while
patients at risk of DM are still selected for systemic
treatments. These strategies are being carefully explored
in clinical trials using risk-stratified approaches directed
by relevant end-points intended to safely return to less
intensive treatments analogous to those used in a previous
era.
SP-0192 Potential of radiation therapy to convert the
tumor into an in situ vaccine
S. Formenti
1
1
Weill Cornell Medical Center of Cornell University, New
York- NY, USA
Radiation therapy contributes both immunogenic and
immunosuppressive
signals
to
the
tumor
microenvironment. Preclinical strategies to enhance the
formers and/or mitigate the latter have demonstrated the
concrete possibility to shift this balancing act toward a
therapeutic success (J Natl Cancer Inst. 2013;105(4):256-
265). Preclinical experiments in several syngeneic mouse
models that mimic the setting of advanced cancer have
demonstrated promise of combining radiation and
immunotherapy. The preclinical data has consistently
found clinical confirmation. Particularly when combined
with immune checkpoint blockade, radiotherapy has
demonstrated to be a powerful adjuvant to
immunotherapy (Clin Cancer Res. 2005;11:728-734).
Clinical examples of synergy between radiation and
immune checkpoint inhibitors have been reported (N Engl
J
Med.
2012;366(10):925-931;
Transl
Oncol.
2012;5(6):404-407; Int J Radiat Oncol Biol Phys.
2013;85(2):293-295; Cancer Immunol Res 2013;1(6):365-
372) and and interim results in our prospective clinical
trial confirm this finding (presented in room 1, May 17
session 051). Currently, multiple clinical trials are
exploring optimal combinations and scheduling of
radiotherapy and immunotherapy. Early evidence from
these trials confirms the hypothesis that radiation can
enhances responses to immune checkpoint inhibitors but
in the majority of patients tumors remain unresponsive,
warranting research to identify markers that predict
response. A recent study testing radiation with ipilimumab
in melanoma suggested that tumor expression of PDL-1
may predict lack of response to radiation and ipilimumab.
However, in lung cancer patients treated with radiation
and ipilimumab we found high PDL-1 expression among
patients achieving durable complete and partial
responses, without addition of PD-1 pathway inhibitors
(ASTRO Proceedings 2015, abstract #149). In fact, higher
expression of immune checkpoints has been hypothesized
as a marker of more immunogenic tumors (Science,
2015,October 9: 207-211). In addition, pre-treatment
mutational load has been found to be associated with
responses to immune checkpoint inhibitors (Science, 2015
Apr 3: 124-8). It will be important to determine if
radiation can compensate tumors with a low mutational
load, by inducing induce de novo T cell priming to multiple
tumor antigens (12) and could, therefore, achieve
responses in the absence of pre-existing neoantigens
(Science 2015;348(6230):69-74). The overall degree of
immune impairment of the patients may also be a critical
predictor of response to radiation + immunotherapy. For
instance, we found the pretreatment neutrophil /
lymphocyte ratio might enable
a priori
selection of
individuals with a propensity to develop abscopal
responses to the combination of radiation and GM-CSF
(Lancet Oncol. 2015 Jul;16(7):795-803). Strategies at
reducing radiation-induced lymphopenia are warranted to
assure adequate availability of naïve T cells when
radiotherapy is harnessed to convert the tumor into an
individualized cancer vaccine. Overall, while radiation has
emerged as a promising partner for immunotherapy and
current research is focusing at identifying tumor and
patient characteristics that can predict which patients
should receive upfront the combination of immunotherapy
with radiotherapy instead of immunotherapy alone.
SP-0193 Quality improvement in radiotherapy:
history, significance and impact of dosimetry audits
J. Izewska
1
1
IAEA - International Atomic Energy Agency, Dosimetry
and Medical Radiation Physics Section, Vienna, Austria
The concept of verification of radiation doses in medical
applications was introduced in early 20th century, not long
after radiation started to be used for treating cancer.
Initially, to estimate the adequate daily fraction of
radiation to be given to patients physicians exposed the
skin of their own arms to radiation to produce the
‘erythema dose’. Since then, the methodologies, dose
measurement tools and radiation therapy equipment have
made a great progress. In 1925 R. Sievert established a
circulating physical department for standardizing the
Roentgen radiation used in cancer therapy in Sweden. The
department found some unreliable dose meters and
identified the need for better protective equipment. At
the same time, the measurements of percentage depth
doses collected during the visits were used as a reference
dataset for the Roentgen facilities in Sweden. Another
example of early dosimetry audits was documented in
Poland; following the idea by Marie Curie, the
Measurement Laboratory was established in 1936 for
radiation dose measurements at Polish hospitals using
radium and
X-ray
beams.
The Dosimetry Laboratory of the International Atomic
Energy Agency (IAEA) was set up in early 1960s with the
aim of the provision of dosimetry audits for radiotherapy
centres worldwide and for ensuring international
consistency in radiation dosimetry. First trial inter-
hospital comparisons were implemented by the IAEA in
1965–1966. In parallel, dosimetry comparisons of Co-60
and high energy beams from early medical accelerators
were conducted among hospitals of France, Sweden, and
in other countries. In USA, the Radiological Physics Center
was established in 1968 to operate as an independent
quality assurance office for multi-institutional cooperative
group clinical trials.
Since 1969, the calibration of radiotherapy beams in 2200
hospitals in 132 countries has been verified by the IAEA
jointly with the World Health Organization (WHO) through
postal dosimetry audits. One important part of the
auditing process is related to resolving dosimetry
discrepancies occurring in the audit; errors are traced,
analysed and corrected. In early years, only approximately
50% audited centres had the acceptable beam calibration.
Over the time, several radiotherapy centres improved
their practices, and the current percentage of acceptable
results exceeds 97%.