Oral Oncology 46 (2010) 439441

Contents lists available at ScienceDirect

Oral Oncology
journal homepage: www.elsevier.com/locate/oraloncology

Review

Advances in radiotherapy for head and neck cancer

S.A. Bhide, C.M. Nutting *
Royal Marsden Hospital and Institute of Cancer Research, London, UK

a r t i c l e

i n f o

Article history:
Available online 20 April 2010
Keywords:
Radiotherapy
Head and neck cancer

s u m m a r y
Radiotherapy and surgery are the principal curative modalities in treatment of head and neck cancer.
Conventional (two dimensional, 2D and three-dimensional conformal radiotherapy, 3DCRT) result in signicant side-effects and altered quality of life. Intensity modulated radiotherapy (IMRT) can spare the
normal tissues, while delivering a curative dose to the tumour bearing tissues. Technical advances like
volumetric intensity modulated arc therapy (VMAT) have helped optimise IMRT further. Image guided
radiotherapy (IGRT) can be used to aid target delineation and also help reduce the PTV margins to further
enhance the therapeutic ratio. Particle therapy using protons provides signicant advantage in terms of
normal tissue sparing and is recommended for small cranial tumours and in radiotherapy for paediatric
patients.
2010 Elsevier Ltd. All rights reserved.

Introduction
Radiotherapy (RT) is an extremely effective treatment for head
and neck cancer, both as a primary modality and as an adjuvant
treatment following surgery. RT causes signicant acute (during
and up to 3 months post-radiation) and late toxicities when used
at doses required to sterilise the loco-regional disease (radical
doses).
The acute toxicities of RT include mucositis, dysphagia, xerostomia, dermatitis and pain. Radiation-induced mucositis of the upper
aero-digestive tract results in signicant morbidity and altered
quality of life (QOL) during radiotherapy.1
The late radiation induced toxicities include xerostomia2 (60
90% incidence), grade 3 dysphagia2,3 (1530%), osteoradionecrosis
(ORN) of the jaws4 (515%), sensori-neural hearing loss5
(4060%) skin brosis and laryngeal cartilage necrosis. The late
radiation toxicity is permanent and results in reduced QOL for
the patient; xerostomia and dysphagia in particular.6
Intensity modulated radiotherapy (IMRT) has been a signicant
technological advance in the led of radiotherapy in recent years,
since it allows sparing of normal tissue while delivering radical
radiation doses to the target volumes.

Benets of IMRT
Intensity modulated radiotherapy (IMRT) is an advanced approach to 3-D treatment planning and conformal therapy. It optimises the delivery of irradiation to irregularly-shaped volumes
* Corresponding author.
E-mail address: chris.nutting@rmh.nhs.uk (C.M. Nutting).
1368-8375/$ - see front matter 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.oraloncology.2010.03.005

and has the ability to produce concavities in radiation treatment

volumes. It allows for greater sparing of normal structures such
as salivary glands, upper aero-digestive tract mucosa, optic nerves,
cochlea, pharyngeal constrictor muscles, brain stem, and spinal
cord.79
Salivary gland sparing using IMRT in various head and neck subsites has been demonstrated in three randomised phase III trials. The
multi-centre study (PARSPORT) that compared parotid sparing IMRT
with standard radiotherapy in patients with oropharyngeal and
hypopharyngeal cancer showed a signicant reduction (40% vs.
74%) in rate of grade 2 xerostomia (LENT-SOMA) in the IMRT arm
at 1 year post-radiotherapy.2 Two phase III randomised controlled
trials, investigating parotid gland sparing using IMRT for patients
with nasopharyngeal cancer showed similar results.10,11 This also
translates into improved QOL for the patients. IMRT also enables
sparing of the pharyngeal constrictor muscles, which are important
for a normal swallow and therefore has the potential to reduce acute
and late radiation induced dysphagia. By virtue of its ability to spare
the cochlea, IMRT has the potential to reduce the incidence of radiation-induced hearing loss. The signicant increase in the burden
of toxicity resulting from RT can be reduced using IMRT.
Escalation of radiation dose may improve outcomes in this
group of patients taking advantage of the steep dose response relationships for squamous cell carcinomas. The initial results from a
phase I dose-escalation study using IMRT with concomitant cisplatin in patients with stage III and IV squamous cell carcinoma
(SCC) of the larynx/hypopharynx showed that dose escalation
was safe and tolerable.12 The 2-year loco-regional control was
higher for dose escalated patients. There was no other signicant
late toxicity of note. Although the patient numbers are small, and
the follow-up short, the results are encouraging and justify further
investigation.13

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S.A. Bhide, C.M. Nutting / Oral Oncology 46 (2010) 439441

Image-guided radiotherapy (IGRT)

IMRT can be optimised further making use of advances in the
imaging techniques, i.e. image-guided radiotherapy (IGRT). This,
in its simplest form, can be used to minimise the geographical
miss resulting from changes in the patient anatomy. Studies have
demonstrated the dosimetric changes resulting from volume
alteration in tumours and organs at risk.1417 Adaptive radiotherapy using regular scanning and planning can reduce the dosimetric uncertainties associated with the volume changes. Radiation
dose escalation (taking advantage of the slope of the dose response curves) could improve the outcomes in advanced head
and neck cancers. Clinical trials that attempted to further intensify radiotherapy using hyperfractionation and/or acceleration
have had to close prematurely or have the radiation schedule
modied due to excessive acute toxicity.18,19 Selective dose escalation based on the biological activity of tumours, might improve
the outcomes without increasing the normal tissue toxicity. Positron emission tomography (PET) enables biological imaging of
tumours, and initial studies using [(18)-F] uoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), which highlights
the proliferating areas of the tumour, have been reported.20 These
studies have shown that FDG-PET guided dose escalation using
IMRT is feasible. Hypoxic regions of tumours are radioresistant
and increasing the radiation dose might help overcome the radioresistance. PET scanning using two radioactive tracers namely
uorine-18-labeled uoromisonidazole (F-MISO) and copper (II)diacetyl-bis(N(4)-methylthiosemicarbazone) (Cu-ATSM) have
been shown to highlight the hypoxic areas of tumours. Preliminary studies escalating the radiation dose to the hypoxic areas
have demonstrated the feasibility of this approach in terms of
acute toxicity.21,22 The PET images could be fused with the planning CT scans and these could be used for biological dose optimisation (as opposed to the currently used dose volume histogram
(DVH) based optimisation during inverse planning IMRT). However, follow-up data for outcomes and toxicity from larger studies
using PET guided dose escalation are required before this approach can be used in standard clinical practise.
Volumated intensity modulated arc therapy (VMAT)
Volumated intensity modulated arc therapy (VMAT) is a newer
technique of delivering IMRT. VMAT delivers IMRT-like distributions in a single rotation of the gantry, varying the gantry speed
and dose rate during delivery in contrast to standard IMRT, which
uses xed gantry beams. This technique has been implemented in
the Eclipse treatment planning software (Varian Medical Systems,
Palo Alto, CA) under the name RapidArc (RA). Planning studies
using RA demonstrate shorter planning and treatment time, lesser
monitor units for treatment delivery, better dose homogeneity and
normal tissue sparing.23,24 There is a lack of data as regards clinical
implementation of this technique.
Particle therapy
Charged particles like protons deposit little energy until they
reach the end of their range (depending on their energy) at which
point most of the energy is deposited in a small area, known as the
Bragg peak. This has advantages in terms of normal tissue sparing,
better dose homogeneity and a reduced dose bath effect (low radiation dose to normal tissue). Intensity modulated proton therapy
(IMPT) allows modulation of the uence and the position of the
Bragg peak, permitting three-dimensional dose distributions.
There are no randomised trials comparing IMPT with IMRT reported as yet. Single centre experiences in certain head and neck

sub-sites have been reported. Combination of photon and proton

therapy for advanced malignant sino-nasal tumours demonstrated
control rates comparable to historical controls using IMRT alone.
The rate of grade 3 oculo-visual toxicity (symptomatic and interfering with activities of daily living, Common Toxicity Criteria)
was 5.6% at a median follow-up of 52.4 months.25 Retrospective
single institution studies in nasopharyngeal and oropharyngeal
cancers have reported on similar outcomes.26 The delivery of proton therapy on a wide scale is restricted by the limited availability
of proton therapy machines due to the nancial resources required.
The current role of proton therapy therefore lies in the treatment of
tumours close to the skull base or spinal cord, and in paediatric patients,27 where proton therapy provides maximum benet in terms
of normal tissue sparing.

Conict of interest statement

None declared.

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