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Hodgkin's lymphoma emerging radiation treatment techniques: trade-offs

between late radio-induced toxicities and secondary malignant neoplasms

Radiation Oncology

2013,

: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)

ISSN

1748-717X

Article type

Research

Submission date

8 November 2012

Acceptance date

20 January 2013

Publication date

30 January 2013

Article URL

http://www.ro-journal.com/content/8/1/22

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Hodgkin’s lymphoma emerging radiation treatment

techniques: trade-offs between late radio-induced

toxicities and secondary malignant neoplasms

Laura Cella

1,2

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

1,2*

Corresponding author

Email: pacerto@yahoo.com

Institute of Biostructures and Bioimaging, National Council of Research (CN

R),

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

Switzerland

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

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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

Keywords

Hodgkin’s lymphoma, Emerging radiotherapy techniques, Radio-induced toxicity, Sec

ond

malignant neoplasm

Background

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

ks.

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

ed.

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].

Methods

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

(CTV

). The CTV

included the upper mediastinal and left supraclavear nodal sites; the CTV