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Hodgkin's lymphoma emerging radiation treatment techniques: trade-offs
between late radio-induced toxicities and secondary malignant neoplasms
Radiation Oncology
:22 doi:10.1186/1748-717X-8-22
Laura Cella (laura.cella@cnr.it)
Manuel Conson (m.conson@gmail.com)
Maria Cristina Pressello (mpressello@scamilloforlanini.rm.it)
Silvia Molinelli (Silvia.Molinelli@Cnao.it)
Uwe Schneider (uwe.schneider@uzh.ch)
Vittorio Donato (vdonato@scamilloforlanini.rm.it)
Roberto Orecchia (roberto.orecchia@ieo.it)
Marco Salvatore (marsalva@unina.it)
Roberto Pacelli (pacerto@yahoo.com)
Article type
Submission date
8 November 2012
Acceptance date
20 January 2013
Publication date
30 January 2013
Article URL
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Hodgkin’s lymphoma emerging radiation treatment
techniques: trade-offs between late radio-induced
toxicities and secondary malignant neoplasms
Laura Cella
Email: laura.cella@cnr.it
Manuel Conson
Email: m.conson@gmail.com
Maria Cristina Pressello
Email: mpressello@scamilloforlanini.rm.it
Silvia Molinelli
Email: Silvia.Molinelli@Cnao.it
Uwe Schneider
Email: uwe.schneider@uzh.ch
Vittorio Donato
Email: vdonato@scamilloforlanini.rm.it
Roberto Orecchia
Email: roberto.orecchia@ieo.it
Marco Salvatore
Email: marsalva@unina.it
Roberto Pacelli
Corresponding author
Email: pacerto@yahoo.com
Institute of Biostructures and Bioimaging, National Council of Research (CN
Napoli, Italy
Department of Diagnostic Imaging and Radiation Oncology, University
“Federico II” of Napoli, Napoli, Italy
Department of Health Physics, S. Camillo-Forlanini Hospital, Roma, Italy
Unit of Medical Physics, Centro Nazionale di Adroterapia Oncologica
Foundation, Pavia, Italy
Vetsussie Faculty, University of Zürich and Radiotherapy, Hirslanden, Aara
Radiotherapy Oncology, Department of Radiology of Radiotherapy, Policlinico
Umberto I, University of Rome La Sapienza, Roma, Italy
Advanced Radiotherapy Center, European Institute of Oncology, Milano, Italy
Purpose of this study is to explore the trade-offs between radio-induc
ed toxicities and second
malignant neoplasm (SMN) induction risk of different emerging radiot
herapy techniques for
Hodgkin’s lymphoma (HL) through a comprehensive dosimetric analysis
on a representative
clinical model.
Three different planning target volume (PTV
) scenarios of a female patient with
supradiaphragmatic HL were used as models for the purpose of this st
udy. Five treatment
radiation techniques were simulated: an anterior-posterior paral
lel-opposed (AP-PA), a
forward intensity modulated (FIMRT), an inverse intensity modulate
d (IMRT), a
Tomotherapy (TOMO), a proton (PRO) technique. A radiation dose of 30 G
y or CGE was
prescribed. Dose-volume histograms of PTVs and organs-at-risk (OA
Rs) were calculated and
related to available dose-volume constraints. SMN risk for breast
s, thyroid, and lungs was
estimated through the Organ Equivalent Dose model considering cell re
population and
inhomogeneous organ doses.
With similar level of PTV
coverage, IMRT, TOMO and PRO plans generally reduced the
OARs’ dose and accordingly the related radio-induced toxicities. H
owever, only TOMO and
PRO plans were compliant with all constraints in all scenarios.
For the IMRT and TOMO
plans an increased risk of development of breast, and lung SMN compared
with AP-PA and
FIMRT techniques was estimated. Only PRO plans seemed to reduce
the risk of predicted
SMN compared with AP-PA technique.
Our model–based study supports the use of advanced RT techniques to succes
sfully spare
OARs and to reduce the risk of radio-induced toxicities in HL patients
. However, the
estimated increase of SMNs’ risk inherent to TOMO and IMRT te
chniques should be
carefully considered in the evaluation of a risk-adapted therapeutic strateg
Hodgkin’s lymphoma, Emerging radiotherapy techniques, Radio-induced toxicity, Sec
malignant neoplasm
In the past decades, treatment improvements have made Hodgkin’s
lymphoma (HL) one of
the most curable malignancies. However, due to the low patients mean
age, the combined use
of potentially harmful therapeutic agents and the efficiency o
f the therapy that allows a high
cure rate with a long life span expectation, late effects of H
L treatment represent an important
and considerable threat for surviving patients. Indeed, the older series
of successfully treated
long term surviving patients showed a high rate of late side ef
fects of therapy including
iatrogenic lung, heart and thyroid diseases [1-3].
Technological advances in HL radiation therapy (RT) [4-11] by hig
h conformal treatments
potentially increase control over organs-at-risk (OAR) dose distr
ibution. Dose-volume
histogram (DVH) predictors in HL patients have been reported for
late side effects such as
radiation pneumonitis [12], hypothyroidism [13], and cardiovascular disease
s [14,15]
supporting the planning optimization procedures so as to limit OAR complication ris
However, considering the low mean age, the high cure rate, and the c
onsequent long survival
expectation of HL patients, caution must be taken in the application of
modern techniques
such as intensity modulated radiotherapy or Tomotherapy because of t
he greater volume of
normal tissue receiving low-to-moderate radiation doses and their i
nherent risk of second
malignant neoplasms (SMNs) that may be significantly higher c
ompared with 3D conformal
radiotherapy [16]. Moreover, the impact on SMN incidence from particle
therapy producing
secondary neutrons causes some concern [17]. Structures with a high pot
ential for the
development of second malignancies, such as lung, thyroid and breast, must be consider
Predicting SMN risk from these newer and sophisticated RT deliver
y techniques is
complicated by their having been only recently introduced and by the
consequent absence of
epidemiological data [18]. As an alternative, biologically-based ma
thematical models can be
used to estimate the risk of SMNs related to a given RT techni
que using organ dose
distribution through dose-volume histograms [19-23]. These models allow t
o compare dose
distributions with regard to the estimated risk of SMNs in the i
rradiated organs as a function
of point dose in the radiotherapy dose range also including fractionation effects.
The aim of this study is to analyze normal tissue sparing capability of differe
nt RT techniques
for one representative supradiaphragmatic HL model case, in parti
cular to explore the trade-
offs between radio-induced toxicities and SMNs induction risk. For this
purpose, we have
conceived three different size planning target volumes (PTVs), ea
ch with different
involvement of OARs such as heart, thyroid, breasts and lungs. We have s
imulated RT plans
using five different delivery techniques. DVHs were then used to pr
edict the impact of the
different analysed RT techniques on late side effects and on SMN i
nduction risk estimated
through the Organ Equivalent Dose (OED) model considering cell repopulat
ion and
inhomogeneous organ doses [20].
Planning CT-scan of a female patient with supradiaphragmatic HL
in standard supine
position with 5-mm slices acquisition was considered. Different involve
d field clinical target
volume (CTV
) size scenarios were generated: small (CTV
), medium (CTV
), and large
). The CTV
included the upper mediastinal and left supraclavear nodal sites; the CTV