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to the target –although inhomogeneous on the inside- with
a rapid dose fall-off in the direction of the surrounding
normal tissue, which is mainly due to the inverse square
law. This, we have to recognise, is not a belief, but simple
and straightforward physics. Consequently, the resulting
‘dosimetry’ compares very favourably with other radiation
therapy techniques. When applied to the selected patient
groups the clinical results in terms of survival and toxicity
are the best you (i.e., the patient) can get, as has been
shown in many clinical and comparative studies.
Notwithstanding these apparent benefits, the numbers of
patients treated with BT show a persistent tendency to
decline, while the use of other techniques such as IMRT,
volumetric arc therapies, and –in near future- particle
therapies increases. This happens especially for those
cancer types for which BT has outstanding prospects, such
as in cervical, prostate, and breast cancer. Evidence for
the benefits linked to a given BT standard of care seems
to be bluntly ignored, but it is unclear for what reasons:
are these economical reasons (time consumption,
reimbursement issues for the institution and the radiation
oncologist), complexity of treatment (invasive
procedures, high skills and QA demands), or lacking
technical solutions compared to other techniques (tissue
inhomogeneity correction in TPS, advanced imaging
facilities for advanced IGBT, BT treatment verification)? It
is very clear that in these areas BT still has to work hard
to make the necessary huge steps forward. Many studies
exploring this are on-going. And all of this is really
feasible! Precisely in the fields mentioned here the GEC-
ESTRO Braphyqs group (started under the ESTRO-ESQUIRE
project in 2001) made significant contributions over the
years of its existence. A strong cooperation was developed
in the entire radiation oncology community, including
clinical and GEC committees, the physics committee of
the ABS and the AAPM-BTSC, together with IAEA and the
Euramet group of standard laboratories in Europe. The
question is now whether or not time is allowed for these
developments to reach the point of being fully introduced
into clinical practice, while other and maybe at the first
sight more ‘sexy’ radiation technology and possibly also
other competing cancer treatment approaches are
knocking on our doors. In all cases, it will be the patient
who deserves her/his optimal treatment strategy. Title:
free to John J. Osborne
Award Lecture: Honorary Physicist Award Lecture
SP-0096 Cognitive perspective in the radiation
oncology physics domain
V. Valentini
1
1
Università Cattolica del Sacro Cuore - Policlinico A.
Gemelli, Gemelli ART, Rome, Italy
Cognitive technology can learn a new problem domain,
reason through the hypotheses, resolve ambiguity, evolve
towards more accuracy, and interact in natural means.
Some prototype showed this approach to be enable to
adapt and make sense of many data: “read” text, “see”
images and “hear” natural speech with context; to
interpret information, to organize it and to offer
explanations of what it means, with rationale for the
conclusions; to accumulate data and to derive insight at
every interaction, indefinitely. The interest of this
evolving technology in radiation oncology is very high.
Radiotherapy is domain in medicine in which modeling
the contents of the clinical choices permeates daily life.
The opportunity to have a physic subdomain in
radiation oncology and the interaction among all the
professionals involved in this oncology field could
represent a great opportunity to benefit of this
approach. Possible implications of the cognitive
approach in radiation
oncology, starting from the physic subdomain, will be
explored.
Symposium: The optimal approach to treat
oligometastastic disease: different ways to handle an
indication quickly gaining acceptance
SP-0097 Clinical approach to abscopal effects
P.C. Lara Jimenez
1
1
Hospital Universitario de Gran Canaria Dr. Negrín,
Radiation Oncology, Las Palmas de Gran Canaria- Ca,
Spain
SBRT is becoming a common approach to cancer
treatment. By using this few, high dose per fraction
schedules tumour responses are higher than predicted.
Indirect cell death would account for this “extra cell kill”
induced
by
high
doses
of
radiotherapy.
These indirect “non targeted” effects of radiotherapy
could be related to vessel damage through radiation-
induced endotelial apoptosis, but also, to an inmune
response to reject the tumour cells. In fact, SBRT is
probably the most convenient, less toxic and more
powerful way to “autovaccinate” patients eliciting
antigen release from dying tumour cells. Endothelial
damage, increased vessel´s permeability, increased tumor
infiltrating lymphocytes and “immune cell death” (ICD)
types as necrosis or mitotic catastrophe that led to the
release of calreticulin, ATP or HMBG-1, are mechanisms
triggering the immune response. Later on, maduration of
dendritic cells, APC-dependent antigen presentation to T
cells in the nodes, microenviroment´s modification and
immune response against the tumour, through interferón
γ release, are already demonstrated.
Besides this local effect, a distant immune-mediated non-
targeted effect in tumor locations away from the
radiotherapy treated disease, is called “abscopal effect”.
Radiation-induced T cell maduration against tumour
antigens “make visible” other distant tumour focii to this
especifically adapted citotoxic lymphocytes (CTL).
Abscopal effect after radiotherapy alone, is uncommonly
observed in the clinical setting, probably due to the
exhaustion of the immune response. The suppressor
microenviroment surrounding the tumur focii, the CD8+
lymphocyte supression and/or PD1/PDL-1 overexpression
could be major mediators of tumour resistance to the
immune attack. Abscopal effect could be raised to clinical
relevance by reverting this scenario, through
reinvigorating the patient´s immune system. Immune chek
point inhibitors (ICIs) are drugs that block the constitutive
regulatory supressor mechanisms designed to prevent
“autoinmune attacks” from the immune sytem, to normal
tissue. These mechanisms are constitutive either in
lymhocytes (CTL4/ PD-1/PD-L1) but also in tumour cells
(PD-1/PDL-1). Then by “supressing the supressors” (using
anti CTL4 , Anti PD-1 or anti PD-L1 antibodies) the immune
system is free of the regulatory supressive signals and
results reinvigorated to respond to antigen stimulii.
Therefore, SBRT autovaccination-mediated antigen
presentation results in increased abscopal effect as the
immune system is reinvigorated by the ICI-mediated
activation. Preclinical and clinical evidence support this
approach. Abscopal effect rate of presentation is
increased when ICIs are combined with SBRT without
increase in toxicity. ICIs toxicity is mainly related to
autoinmune reactions as hypophysitis, colitis etc and
should be carefully monitored. Dose reduction, halt drug
administration, systemic corticosteroids or in severe
cases, anti-TNF
a
therapy should be taken in to account.
But still some questions remain to be solved, namely, the
best SBRT schedule, the temporal integration of SBRT and
ICIs and the combinaton of SBRT and more tan one ICIs.