Review
Oncology Received: October 26, 2017
DOI: 10.1159/000489217
Locoregional Control and Toxicity in Head and
Neck Carcinoma Patients following Helical
Tomotherapy-Delivered Intensity-Modulated
Radiation Therapy Compared with 3D-CRT Data
Olalla Santa Cruz a Pelagia Tsoutsou a Cyril  Castella b Kaouthar Khanfir b
Sandro Anchisi b Salim  Bouayed b Oscar  Matzinger c Mahmut Ozsahin d
a HôpitalNeuchâtelois de La Chaux-de-Fonds, La Chaux-de-Fonds, Switzerland; b Centre Hospitalier du
Valais Romand, Sion, Switzerland; c Hôpital Riviera-Chablais, Vevey, Switzerland; d Centre Hospitalier Universitaire
Vaudois, Lausanne, Switzerland
Keywords
Head and neck cancer · Helical tomotherapy ·
Intensity-modulated RT toxicity
Abstract
Objectives: To assess the feasibility and efficacy of intensity-
modulated radiation implemented with helical tomothera-
py image-guided with daily megavoltage computed tomog-
raphy for head and neck cancer. Methods: Between May
2010 and May 2013, 72 patients were treated with curative
intent. The median age was 64 years, with 57% undergoing
definitive and 43% postoperative radiotherapy. Primary tu-
mour sites were oral cavity (21%), oropharynx (26%), hypo-
pharynx (20%), larynx (22%), and others (11%). Staging in-
cluded 4% stage I, 15% II, 26% III, 48% IVa, and 7% IVb. Radio-
therapy was combined with chemotherapy in 64%. Primary
endpoint was locoregional control, and secondary end-
points survival and toxicity. Results: Median follow-up was
20 months, with 11 locoregional recurrences. Three-year dis-
ease-free survival was 58% and overall survival 57%. In the
multivariate analysis, age under 64 years, no extracapsular
© 2018 S. Karger AG, Basel
E-Mail karger@karger.com
www.karger.com/ocl
Accepted after revision: April 11, 2018
Published online: June 12, 2018
extension, postoperative radiotherapy, induction chemo-
therapy, and non-oral cavity tumour were significant favour-
able prognostic factors for disease-free-survival. The overall
incidence of acute grade ≥3 toxicities were mucositis 32%,
pain 11%, xerostomia 7%, dysphagia 53%, radiodermatitis
44%, and osteonecrosis 1%. Late grade ≥3 toxicities were
fibrosis 6%, dysphagia 21%, fistula 1%, and skin necrosis 1%.
Conclusions: Intensity-modulated radiation with helical to-
motherapy achieved respectable locoregional control and
overall survival, with acceptable toxicity, in head and neck
cancer patients. © 2018 S. Karger AG, Basel
Introduction
Radiation therapy (RT) is a mainstay of curative treat-
ment for head and neck cancer (HNC) patients, com-
bined or not with surgery. Many regimens have been eval-
uated in an attempt to improve locoregional and overall
survival (OS) in these patients. The MARCH meta-anal-
ysis [1] showed improved survival rates with altered frac-
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Kaohsiung Medical University Library
Dr. Olalla Santa Cruz
Hôpital Neuchâtelois de La Chaux-de-Fonds
Rue de Chasseral 20
CH–2300 La Chaux-de-Fonds (Switzerland)
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E-Mail santacruzolalla @ gmail.com
tionation compared to standard radiotherapy, with an ab-
solute benefit of 3–4% at 5 years. The benefit was signifi-
cantly higher with hyperfractionated radiotherapy (8% at
5 years) than with accelerated radiotherapy. New tech-
niques are now achieving greater precision in RT by im-
proving dose delivery, optimising non-uniform beam in-
tensities and by decreasing the radiation dose to the nor-
mal tissues.
Intensity-modulated RT (IMRT) is an attractive treat-
ment strategy for HNC patients because of dose distribu-
tion conformity to tumour topography while simultane-
ously limiting normal tissue exposure to relatively high
radiation doses [2]. Sparing non-target areas has led some
to assume that IMRT reduces toxicity compared with
3-dimensional conformal RT (3DCRT) [3].
Evidence on the comparative effectiveness of RT mo-
dalities for HNC is limited and lacks uniformity regard-
ing 3DCRT versus IMRT. In a recent US update, new
moderate-strength evidence found reduced late xerosto-
mia with IMRT compared with 3DCRT, with no relative
change in other adverse events or quality of life [4]. How-
ever, the high conformity of this technique can increase
the risk of recurrence due to geographic miss [5].
Toxicity can also affect radiotherapy compliance and,
hence, disease control. In the TROG 02.02 trial, there was
a 20% difference in the 2-year OS between deficient and
compliant RT [6].
At locoregionally advanced stages, concomitant
chemoradiotherapy (CRT) has been shown to improve
survival and is considered the standard of care [7]. There
is no evidence from randomised trials suggesting that
Tax-PF followed by RT (± concomitant chemotherapy) is
superior to concomitant CRT [8, 9].
Therefore, this retrospective study was undertaken
with the aim of quantifying the toxicity, related to dosi-
metric parameters.
Methods
Patients and Tumour Characteristics
Seventy-two HNC patients were treated with curative helical
tomotherapy (HT) between May 2010 and May 2013. These cases
were extracted from the Radiation Department’s patient registry
at Centre Hospitalier du Valais Romand and retrospectively re-
viewed. Patients were diagnosed by panendoscopy and staged ac-
cording to the American Joint Committee on Cancer (AJCC) stag-
ing system (7th ed.) with CT, MRI, and PET-CT imaging. All tu-
mours were histologically confirmed. The treatment modality was
defined following a multidisciplinary committee discussion. Pa-
tients received definitive or postoperative RT with or without che-
motherapy. Clinical data, treatment, and dosimetric parameters
were retrospectively reviewed and evaluated as prognostic factors.
2 Oncology
DOI: 10.1159/000489217
Treatment Technique
All patients were treated with HT (Accuray, Sunnyvale, CA,
USA) using 6-MV photon beams and daily fan-beam MV CT im-
age guidance (image guidance radiotherapy). HT delivers highly
modulated IMRT plans in a helical way using a binary multi-leaf
collimator (MLC). The MLC consists of 64 interleaved leaves with
a nominal width of 6.25 mm at the isocentre. Before treatment de-
livery, all plans underwent a phantom-based quality assurance
(QA) validation to verify the delivered pattern and the calculated
dose. The phantom used was the Octavius phantom (PTW,
Freiburg, Germany), which acquires a dose plane with 729 ion
chambers. Our QA acceptance criteria were >95% of the measured
points having a gamma below 1 (3% of max. dose, 3 mm).
Statistical Analyses
Descriptive statistics were used to generate data for patient and
treatment characteristics.
The statistical analysis was performed using JMP, version 10.0.
All tests to determine statistical significance were two sided, and
the statistical significance was defined as a p value <0.05. Discrete
variables were compared with the χ2 test and continuous variables
with the t test. Differences between medians were assessed using
the Wilcoxon test. Crude rates were used in calculating local, re-
gional, and distal recurrence rates. Survival curves, rates of recur-
rence and toxicity incidences were plotted based on the Kaplan-
Meier method, and compared (univariate analyses) using the log
rank test. Multivariate analysis was performed using nominal lo-
gistic regression analysis to adjust for explanatory confounding
prognostic variables with p value <0.10 on the univariate analyses.
Toxicity Assessment and Response
Acute toxicities were graded according to the Common Termi-
nology Criteria for Adverse Events (CTCAE, version 3.0). A per-
cutaneous endoscopic gastrostomy tube was placed at the start of
treatment in patients likely to require tube-feeding for longer than
6 weeks after RT. All patients were evaluated by their radiation
oncologist and a nutritionist at least once a week during the RT
course. Late toxicity was graded according to the Radiation Ther-
apy Oncology Group/European Organisation for Research and
Treatment of Cancer (RTOG/EORTC) late radiation morbidity
scoring system. Severe early and chronic toxicities (G3–4) were
correlated with common risk factors.
Response evaluation consisted of a physical examination, CT/
MRI scan and, when needed, with a FDG-PET/CT scan 3 months
after treatment. Patients were regularly followed up every 2 months
for the first 2 years, every 3 months for the third year, every 6
months for the fifth year, and then once a year. The frequency of
radiologic assessment was at the discretion of the physician.
Dosimetric Data
The definitive RT dose was 69.3–70 Gy, and 60–66 Gy in the
postoperative setting. Dose distributions to PTVs (planned target
volumes) and OARs (organs at risk) were correlated with severe
toxicities and treatment effectiveness, using Cox regression and
contingency analysis. We evaluated the average, median dose,
D2%, D95%, and D98% for PTVs (PTV1: 66–70 Gy, PTV2: 52.8–
60 Gy, and PTV3: 52.8–54 Gy). Elective radiation delivered in
HNC treatment follows the Groupe d’Oncologie Radiothérapie
Tête et Cou (GORTEC) guidelines at our institution. For OARs,
the organ volume, mean and maximum doses were reported. Spi-
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Santa Cruz et al.
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nal cord, brainstem, parotid glands, submandibular glands, man- Table 1. Patients’ characteristics
dible, cochlea, oral cavity, larynx, oesophagus, and brachial plexus
(when needed) were outlined in all patients. Total radiation treat- Age, years
ment time (TTT) was reported, with 10 patients having been re- Median 64
planned during RT due to anatomical changes. Range 41–91
Gender
Male 56 (78%)
Female 16 (22%)
Results Tobacco history
Current, during RT 35 (49%)
Patient and Tumour Characteristics Former, patient stopped prior to RT 26 (36%)
The baseline patient and tumour characteristics are Never 8 (11%)
Unknown 3 (4%)
shown in Table 1. Alcohol history
All patients had primary non-metastatic tumours, and Yes, >80 g/day 44 (61%)
the median follow-up was 20 months (range, 9–39 No 26 (36%)
Unknown 2 (3%)
months). The majority of patients had squamous-cell car- Autoimmune disease
cinoma (92%), which was poorly differentiated in 36%. A Yes 7 (10%)
total of 57% underwent definitive RT and 43% postop- No 65 (90%)
erative RT. Boost technique consisted of a simultaneous- Tumour characteristics
ly integrated boost in 47% and a sequential boost in 53% Staging modality
of patients. In the postoperative group, 54.8% of patients CT scan
Yes 54 (75%)
had microscopically involved margins, while 96.7% had No 18 (25%)
ipsilateral lymphadenectomy, and 51.6% contralateral. MRI
Two patients treated with RT alone had debulking sur- Yes 50 (70%)
No 21 (30%)
gery, and 1 patient an adenectomy. Treatment was com- 18FDG PET/CT
bined with chemotherapy in 67% of patients. The chemo- Yes 41 (57%)
therapy regimen used was induction in 2, concomitant in No 31 (43%)
36 and induction + concomitant in 10. Synchronous tu- 18FDG PET/CT SUVmax
Primary tumour, mean ± SD 14±0.98
mours were diagnosed in 7% patients (other H&N local­ Lymph nodes, mean ± SD 10±0.96
isation, lung and prostate cancer). Histology
Squamous-cell carcinoma 66 (92%)
Adenocarcinoma 2 (3%)
OS and PFS Adenoid cystic carcinoma 2 (3%)
At the time of the analysis, 19 patients had died, and Small-cell carcinoma 1 (1%)
actuarial OS rates at 1, 2, and 3 years were 90% (95% CI: Other 1 (1%)
83–97%), 73% (95% CI: 61–85%), and 57% (95% CI: 39– Histology differentiation
76%), respectively. Median survival time was 17 months Moderate 35 (50%)
(95% CI: 8–26 months) (Fig. 1). Poor 26 (37%)
Unknown 9 (13%)
Seven patients had primary uncontrolled tumour or Extracapsular extension or >2 cm
progression 3 months after treatment. Progressive disease Yes 28 (39%)
(local, regional, and/or systemic) occurred in 15 patients No 44 (61%)
Tumour localisation
(21%) with a median interval of 14 months (range, 10–24 OC 15 (21%)
months). Recurrences were confirmed with biopsy in 11 OP 19 (26%)
patients, with CT scan in 2 patients, and with FDG-PET/ HP 14 (20%)
CT in another 2. In patients who progressed, the primary LAR 16 (22%)
Others 8 (11%)
tumour location was as follows: oral cavity in 5 patients, TNM stage (7th ed.)
oropharynx in 3, hypopharynx in 3, and larynx in 4. Elev- I 2 (3%)
en patients developed a locoregional recurrence after II 11 (15%)
III 19 (26%)
treatment. Local recurrence was observed in 8 patients IVA 35 (49%)
(11%), 6 within the PTV; there were 6 regional recurrenc- IVB 5 (7%)
es (8%), 4 within the PTV. Distant progression with new
metastases occurred in 5 patients (7%), all of whom had OC, oral cavity; OP, oropharynx; HP, hypopharynx; LAR, larynx.
progression within the lung. Most patients also pro-
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Control and Toxicity in H&N Carcinoma Oncology 3

Patients: HT-IMRT versus 3D-CRT DOI: 10.1159/000489217
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 Color version available online
1.0 1.0

0.8 0.8

Disease-free survival
Overall survival

0.6 0.6

0.4 0.4

0.2 0.2

0 0
0 12 24 36 0 12 24 36
Months Months

1.0 1.0

0.8 0.8
Locoregional control

0.6 Distant control 0.6

0.4 0.4

0.2 0.2

0 0
0 12 24 36 0 12 24 36
Months Months

Fig. 1. Overall survival, disease-free survival, and locoregional and distant control in 72 head and neck cancer patients.

gressed in multiple sites, such as the sternum, the para-
gastric nodes, the liver and the brain.
The 3-year disease-free survival (DFS) was 58% (95%
CI: 43–73%), and disease control was 65% (95% CI: 49–
80%). Local control was 71% (95% CI: 57–86%), regional
control 91% (95% CI: 84–98%), and distant control 88%
(95% CI: 76–99%). A further 7 patients received salvage
surgery, 3 of whom died of disease progression.
Our data showed that an oral cavity primary tumour
and age ≤64 years were statistically significant predictors
for DFS in univariate analysis (p < 0.05 for both). Patients
aged over 64 years had a better outcome than younger
patients, with 3-year DFS rates of 69 versus 47% (p =
0.01). Oral cavity location of primary tumour was a sig-
nificant predictor of poorer DFS (p = 0.005). Sex, lifestyle
habits, TNM, and tumour histology characteristics did
not influence DFS (Table 2).
A multivariate analysis including five variables was
performed to evaluate the impact of these variables on a
patient’s likelihood of disease relapse. The five variables
included in the model were age > 64 years, an invaded
lymph node with extracapsular extension or bigger than
2 cm, definitive RT, chemotherapy type, and oral cavity
tumour localisation. Of these variables, age over 64 years,
lymph nodes with nodal extracapsular extension, defini-
tive RT, non-induction chemotherapy, and oral cavity
primary tumour were associated with a significant lower
DFS (Table 3).
OARs, PTVs, and Toxicity
Dose-volume histograms (DVHs) of the PTVs and
OARs are described in Table 4. Larger primary PTVs
(>131 cm3) resulted in significant higher early dysphagia
rates (64.8 vs. 35.14%; p = 0.02) and late dysphagia rates
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4 Oncology Santa Cruz et al.

DOI: 10.1159/000489217
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Table 2. Univariate analysis for disease-free survival (DFS) Table 3. Multivariate Cox analysis for disease free-survival

Variable 3-year DFS Variable RR 95% CI p

n DFS, % 95% CI p
Age >64 years 2.14 1.7–2.6 0.03
Capsular extension or >2 cm 1.55 1.1–2 0.005
All patients 72 58 43–73
Definitive/postoperative 1.47 1–1.9 0.003
Sex
Chemotherapy type (induction better) 1.49 0.7–2.26 0.05
Female 16 58 31–84 0.6
Oral cavity vs. other primary 1.27 0.78–1.75 0.002
Male 56 58 41–75
Age
>64 (median) years 36 47 28–65 0.01
≤64 years 36 69 47–91
Smoker
Yes (current or former) 35 52 31–73 0.3 dysphagia and dermatitis (p < 0.0001) in the multivariate
No (never or unknown) 37 64 45–83 analysis.
Alcohol Dosimetric values showed that the mean ipsilateral dose
Yes 44 52 30–74 0.9 delivered in the parotid gland was 21 Gy, and 16 Gy in the
No 28 65 46–84
contralateral one. Likewise for the submandibular glands,
Autoimmune disease
Yes 7 71 38–104 0.9 the level I elective radiation delivered a mean dose of 44 Gy
No 65 57 42–72 ipsilaterally and 36 Gy contralaterally. The larynx was con-
Prior cancer history toured in tumours without infiltration, with a mean dose
Yes 11 60 29–91 0.8 of 29 Gy. Maximum doses to spinal cord, brainstem, and
No 61 57 40–73 mandible were 35, 20, and 56 Gy, respectively.
TNM The DVHs for the salivary glands were evaluated by
I/II 13 68 35–101 0.7 comparing the mean relative volumes at selected dose
III 19 63 41–85
values between patients with and without toxicities. The
IV 40 52 29–75
Differentiation ANOVA analysis showed no statistical significance be-
Poor 26 52 27–77 0.5 tween these two factors. The contoured volume of OARs
Other 46 62 45–79 was not associated with toxicity.
Histology The reported severe early toxicities were mucositis
Squamous 66 56 40–72 0.2
(31%), pain (11%), xerostomia (7%), dysphagia (52%),
Other 6 75 32–117
Localisation dermatitis (45%), eye or auditory disorders (3%), and
Oral cavity 15 40 15–65 0.005 lymphedema (1%). One case of osteonecrosis was ob-
Other 57 64 48–80 served within 3 months after treatment in a patient with
Chemotherapy a limited laryngeal tumour. This complication was prob-
Induction 12 82 60–104 0.1 ably not associated with the radiation treatment, because
Other 60 53 37–69
Radiotherapy DVH revealed that the necrotic region did not receive
Definitive 41 49 29–69 0.1 doses >30 Gy. Severe chronic dysphagia occurred in 21%
Postoperative 31 67 45–89 of patients, 1% had permanent eye or auditory disorders,
Extracapsular extension or >2 cm 5% severe cutaneous fibrosis, and 1% flap necrosis more
Yes 28 55 36–74 0.2 than 6 months after ending radiotherapy.
No 44 61 42–80

Total Treatment Time

(47.9 vs. 52%; p = 0.059). There was a trend for larger pri-
mary tumour PTVs to correlate with decreased outcomes
compared with smaller tumours (OS at 3 years, 36 vs.
74%; p = 0.23). Severe chronic toxicities were observed in
36% of recurrences. Age was associated with acute severe
toxicity. Older patients (> 64 years) had more pain and
xerostomia (p < 0.0001), and younger patients had more
Twenty-five patients (35%) started treatment on Mon-
day and 21 (29%) at the end of the week (Thursday or
Friday). Treatment interruptions occurred in 64 (89%)
patients. Only 33% of patients followed the standard
treatment duration (< 47 days), 56% had a minor TTT
prolongation deviation (47–54 days), and 11% a major
TTT prolongation (> 54 days). TTT was not associated
with acute or late severe toxicities or OS. Patients re-
planned during treatment (n = 10) experienced more
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Control and Toxicity in H&N Carcinoma Oncology 5

Patients: HT-IMRT versus 3D-CRT DOI: 10.1159/000489217
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Table 4. Volume and dose distributions of planned target volumes (PTVs) and organs at risk

Parameter n Mean SD Parameter n Mean SD

PTV1 68 Contralateral eye 16

Volume, cm3 154 112 Volume, cm3 9 2
Mean dose, Gy 100 0.7 Mean dose (Gy) 2 3
D98% 97 1.4 Max (Gy) 7 8.6
D95% 98 1 Brainstem 35
D2% 116 11 Volume, cm3 18 9.7
PTV2 68 Mean dose, Gy 8 8
Volume, cm3 382 284 Max, Gy 20 12
Mean dose, Gy 116 8 Spinal cord (partial volume of
D98% 99 5 involved site) 69
D95% 101 4 Volume, cm3 29 11
D2% 127 18 Mean dose, Gy 15 6
Ipsilateral parotid 67 Max, Gy 31 5
Volume, cm3 22 7 Mandible 47
Mean dose, Gy 21 10 Volume, cm3 63 15
Median dose, Gy 21 27 Mean dose, Gy 29 11
Contralateral parotid 70 Max, Gy 56 12
Volume, cm3 23 8
Larynx 33
Mean dose, Gy 16 9
Volume, cm3 33 16
Median dose, Gy 13 9
Mean dose, Gy 29 13
Ipsilateral submandibular gland 34 Median dose, Gy 28 13
Volume, cm3 6 3 Brachial plexus 9
Mean dose, Gy 44 15 Volume, cm3 22 27
Median dose, Gy 43 16 Mean dose, Gy 37 7
Contralateral submandibular gland 42 Max, Gy 58 7
Volume, cm3 7 6 Oral cavity 29
Mean dose, Gy 36 19 Volume, cm3 51 30
Median dose, Gy 36 20 Mean dose, Gy 23 11
Ipsilateral cochlea 13 Max, Gy 42 18
Volume, cm3 0.3 0.1 Thyroid 18
Mean dose, Gy 13 14 Volume, cm3 19 14
Max, Gy 46 Mean dose, Gy 38 19
Contralateral cochlea 13 Max, Gy 52 19
Volume, cm3 0.3 0.2 Oesophagus (partial volume of
Mean dose, Gy 13 14 involved site) 19
Max, Gy 37 Volume, cm3 19 25
Ipsilateral eye 15 Mean dose, Gy 16 8
Volume, cm3 8 1 Max, Gy 48 19
Mean dose, Gy 3 4
Max, Gy 9 12

acute toxicity (pain and xerostomia, p < 0.01) with no im-
provement in locoregional control or OS. Replanning in-
duced significant longer TTT (p = 0.0001).
Discussion
A patient cohort was studied in our centre, treated
with IMRT in combination with surgery (43%) or che-
motherapy (64%). This study focused on patterns of
toxicity and recurrence after IMRT treatment com-
pared to 3D-RT. There were 15% (11 patients) locore-
gional recurrences as initial failure sites, with 7% (n = 8
patients) local recurrences, 4% (n = 6) regional, and 3
both local and regional, at a median follow-up of 1.6
years. Recurrence sites were projected on the initial RT
planning CT scan, to evaluate IMRT locoregional treat-
ment failure. All recurrences were within the high-risk/
elective planning target volume except for those in 2
patients.
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6 Oncology Santa Cruz et al.

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 These findings can be compared with the results pub-
lished by the GORTEC group in 2012 [10], where a big-
ger, but also heterogeneous group of patients, a part of
whom received a postoperative IMRT treatment (46%)
and a part of whom (37.5%) received concurrent chemo-
therapy. In this study, 12.2% locoregional recurrence
rates were observed at a median follow-up of 25.3 months.
Three of these recurrences were marginal and one was
outfield.
Regarding survival data, a 2-year OS rate of 73% was
reported in a review of patients, 81% of whom present-
ing locally advanced stages. In a similar population,
more promising results were reported by Yao et al. [11],
with a 2-year OS rate of 85% in a population presenting
with locally advance stages in 85.4% of the patients
studied.
The published clinical results demonstrate equiva-
lence or non-inferiority of IMRT in terms of tumour
control or survival in any head and neck site [9, 12–16],
while IMRT plays a significant role on the reduction of
radiation-induced toxicity [17–20]. According to our
analysis, 53% of patients had severe acute dysphagia.
Chronic remaining dysphagia was observed in 21% of
them. Xerostomia is known as the main chronic toxicity
in head and neck patients after radiation treatment. Its
evaluation is difficult to standardise. Several clinical trials
established a correlation between parotid-sparing mean
dose and salivary flow preservation after irradiation.
Mean doses below 25–30 Gy were associated with com-
plete recovery of salivary flow [10, 21–23]. In our study,
where generally large PTV volumes were treated, pre-
serving parotid glands with a mean dose of 21 Gy at the
ipsilateral gland and 16 Gy at the contralateral one was
possible with HT IMRT.
Another risk factor for toxicities was age, which was
significantly associated with the occurrence for acute se-
vere toxicity. Younger patients had more dysphagia and
dermitis. Considering younger patients are more suitable
candidates for chemotherapy treatment, these results are
in accordance with the GORTEC trial, where severe mu-
cositis was significantly associated with chemotherapy
and more advanced local stages.
Limitations to the interpretation of our results are re-
lated to the retrospective nature of our study, its small
sample size with heterogeneous stages and multimodality
treatments. However, our data add to emerging informa-
tion about toxicity profiles and recurrence patterns with
a technique (tomotherapy IMRT) that is not widely used
yet and where data are lacking.
Control and Toxicity in H&N Carcinoma
Patients: HT-IMRT versus 3D-CRT
Conclusions
Given the limited OS and DFS in patients with HNC
(most presenting with advanced disease and significant
morbidity associated with RT), IMRT appears to be an
excellent treatment option to obtain an optimal tumour
conformation and to spare normal tissues. This retro-
spective analysis reports that HT improves the coverage
of PTV and preserves the salivary glands, even in cases of
large volumes. Radiotherapy delivered with HT achieved
respectable 3-year local and regional control (71 and 91%,
respectively) and OS (57%) in HNC patients, with accept-
able late toxicity (21% severe dysphagia needing continu-
ous tube feeding). Differences in toxicities according to
age may be related to other factors such as HPV (younger
patients) and basal salivary gland atrophy (older pa-
tients). Consistent with previous reports, the worst out-
comes were found in patients harbouring tumours of the
oral cavity.
Our findings showed that local and regional recur-
rences were mainly within the target RT volume (PTV).
This suggests a lack of radiation effectiveness in some ag-
gressive tumours, since our results provide evidence of
good PTV coverage using tomotherapy IMRT. Systemic
progression was always preceded by lung metastases. In-
duction chemotherapy was associated with more favour-
able DFS than concomitant chemotherapy in this study,
but this conclusion remains questionable due to the small
sample size and retrospective nature of the study.
Despite the large number of patients with a longer
treatment period, we did not observe a negative impact
on local control and OS. Conversely, patients in whom an
adaptive plan had to be employed (due to greater toxicity
with bigger anatomical changes) did not present im-
proved toxicity or OS rates.
Statement of Ethics
This study did not require informed consent or review/approv-
al by the appropriate ethics committee.
Disclosure Statement
The authors declare that there was no funding for this study
and they have no competing interests.
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DOI: 10.1159/000489217
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