Introduction
Laryngeal cancers constitute 1.1% (157.000 new cases)
of all new cancer cases worldwide. Laryngeal cancers are more common in men than in women. The male/
female ratio is 7/1.[] Approximately 2/3 of the laryngeal
cancers arises from the glottic region, while
between 80% and 85% of glottic cancers are in the early-stage (T1-T2N0M0) at the time of diagnosis.[]
Providing larynx and voice preservation is an important
factor in the choice of treatment.[] In EGL cancer,
surgical and radiotherapy treatment techniques
give similar survival results, and their superiority
over each other remains controversial.[] However,
to many patients, radiotherapy is recommended since
it provides better voice preservation.[] Patients with
EGL cancer are under high risk of cardiovascular disease
and metachronous secondary head and neck cancer
since they have a smoking history.[,] These risks
should be considered in the selection of radiotherapy
techniques. Although using conventionally used parallel-
opposed wedge field techniques (2 Dimensional
Radiotherapy-2D RT, 3 Dimensional Conformal Radiotherapy-
3D-CRT), high local control rates can be
reached, tissues around the tumor receive high doses
uprising the risk of side effects due to irradiated the
critical organs and their possible subsequent deterioration.[,] The re-irradiation of the neck may cause
critical organ doses to exceed tolerance doses. Several
studies showed that the traditionally used parallel-opposed
field techniques produce high doses on carotid
vessels and may cause late cerebrovascular diseases,
vascular stenosis, and ischemic strokes.[,] As
a part of the late side effects of radiation, hyperthyroidism
and hypothyroidism may also be seen.[] By
the protection of the spinal cord and submandibular
glands, the risk of myelopathy and dry mouth may be
reduced.[,] Lower radiation exposure on these
structures may reduce the radiation damage and side
effects. Intensity Modulated Radiation Treatment
modalities (such as Dynamic Intensity Modulated
Radiotherapy (D-IMRT), Intensity Modulated Arc
Radiotherapy (IMAT), Helical Tomotherapy (HT))
using more advanced technology can maintain high
levels of local control with lower normal tissue exposure
than conventional radiotherapy and provides
sharp dose decreases at the target volume boundaries.
[] These modern techniques provide a more conformal
dose distribution on tumor volume while providing
low dose exposure on normal tissues, reducing
the risk of normal tissue damage from high radiation
exposure. However, healthy tissue volume with a low
dose is particularly important for radiation-induced
secondary cancer risk and an important concern for
IMRT techniques is that they increase in normal tissue
volume with low doses. It is estimated that the incidence
of secondary cancers can be almost doubled
with IMRT techniques compared to conventional
techniques.[]
Ekici et al. administer a treatment dose of 63 Gy
to PTV in their study comparing four techniques for
T1N0 EGL cancer radiotherapy. However, they did
not perform any study to increase the dose beyond 63
Gy.[] Using IMRT treatment techniques (D-IMRT,
IMAT, HT), it is possible to increase the treatment
dose of EGL. This study aims to investigate the treatment
plan parameters and Organ at Risk (OAR) doses
obtained by 3-D CRT, D-IMRT, IMAT and HT techniques
to increase the treatment dose from 63 Gy to 70
Gy in the radiotherapy of EGL cancer.
Methods
DICOM sets of 15 previously treated early glottic laryngeal
cancer (T1-T2, N0, M0) patients were obtained
from the archives of our institute. This study was approved
by the Ethics committee before the start (Date:
01.12.2017, Registration number: 2017/1399). Treatment
volumes and critical organs were contoured by a
radiation oncologist according to the guidelines of our
institute. The planning target volume-70 Gy (PTV-70)
was created by giving a 1-cm margin to the gross tumor
volume (GTV) in all axes. A 5-mm margin was given
to larynx in all axes to create the PTV-63 volume. Mean
treatment volumes were 95.56 cm3, 28.26 cm3 for PTV-
63 and PTV-70, respectively.
The prescription dose was defined as 2.12 Gy per
fraction to a total of 33 fractions. At least 95% of the
PTV-63 and PTV-70 treatment volumes (D95%) were
normalized to be administered 63 Gy and 70 Gy, respectively.
The dose homogeneity of treatment volumes
was aimed to be between 95-107%. Conventional-
boost technique (a sequential boost) was used
for 3D-CRT plans and Simultaneous-Integrated-Boost
(SIB) technique was used for D-IMRT, IMAT and HT
plans. 3D-CRT, D-IMRT, and IMAT plans were performed
using an Eclipse treatment planning software
version 15.6 (Varian Medical Systems Inc., Palo Alto,
CA). TomoHDA™ treatment planning software version
2.0 was used for HT plans.
For the 3D-CRT plans, parallel opposed-lateral
fields (at 900 and 2700) were used for PTV-63 volumes
and wedge filters (350 and 450 angles) were used
to provide dose homogeneity. After the PTV-63 plan
was created, oblique fields from the anterior part of the
neck (coplanar or noncoplanar) were used according
to the PTV-70 position. PTV-63 and PTV-70 plans
were combined to obtain cumulative-dose volume histograms
(c-DVH). The c-DVHs and isodose lines were
used to examine the plan sum. By examining the parameters shown on the plan sum, PTV-63 and PTV-70
were normalized to the adequate isodose line so that
95% of the PTVs received the prescribed doses. A bolus
was not necessary for these plans.
The 5-field D-IMRT plans 00, 510, 1020, 2550, 3060
oblique fields were used for 14 patients, and the fields
of 00, 400, 800, 1200, 3200 were used to remove the shoulders
from the treatment fields for one patient.
Two full arcs were used in the IMAT plans. The first
arc was started with 180.10-179.90 angles and the other
arc was set to rotate on the same plane in the opposite
direction (179.90-180.10) of the first arc. To avoid the
interleaf leakage radiation, the primary and secondary
fields were given a 3000 and 3300 collimation angle, respectively.
A dose calculation algorithm was used for
3D-CRT, D-IMRT, and IMAT plans. Photon Optimizer
(PO) and Progressive Resolution Optimizer (PRO) algorithms
were utilized for the D-IMRT and IMAT, respectively.
For HT in all plans, the width of the field was 2.5
cm, the modulation factor was 2.5, and the pitch factor
was 0.446. The dose calculations for HT plans were
performed using the Convolution/Superposition algorithm.
All plans were generated with 6-MV photons
using a multileaf collimator. Planning parameters for
critical organs in the process of optimization for DIMRT,
IMAT and HT techniques: Spinal cords Dmax<20
Gy, Carotid arteries Dmean<35 Gy and V35,50,63Gy <35,
50, 63(%), Thyroid glands Dmean<30 Gy and V30,50Gy<
30,50(%), Submandibular glands Dmean<39 Gy were
used. As an example of treatment plans, the dose distribution
of an individual patient plan obtained from
the four treatment modalities is shown in Figure 1.
Fig 1: The dose distribution of an individual patient
plan obtained from the four treatment modalities.
D2% (near-max), D98% (near-min) and D50% (dosemean)
were analyzed in evaluation of PTV volumes
(doses received by 2%, 98% 50% of the treatment volumes)
as described in ICRU 83 guidelines. For Homogeneity
Index (HI); HI=(D%2-D%98)/D%50 formula and
for Conformity Index (CI); CI=Vri/TV (Where Vri is the
volume of reference isodose and TV is the treatment
volume covered by reference isodose line) formula
were used. HI values approximating to zero indicate a
more homogeneous dose distribution in the target volume
(zero is the ideal value). The ideal CI value is equal
to 1.[]
For the statistical comparison, the One-Way
ANOVA test was employed when parametric conditions
were provided; otherwise, the Kruskal-Wallis test
was used. When parametric conditions were provided
for pair-wise comparisons, the Bonferroni test was
used; otherwise, the Mann-Whitney U test was used. The P-value of <0.05 is considered statistically significant.
The IBM SPSS 24.0 version (SPSS Inc., IL, USA)
was applied for statistical comparison. Table 1 and
Table 2 indicate comparison and analysis data of PTVs,
OARs, and MU.
Table 1: D2%, D98%, D50%, HI, CI and MU values for PTV-63 Gy and PTV-70 Gy and their statistical results (The values are the average data of the 15 patients)
Table 2: OAR dose parameter values and their statistical results for the four treatment techniques (The values are the average of 15 patients" data)
Results
Evaluation of Treatment Plan Parameters for PTV
The results of the PTV comparison of four different
techniques are shown in Table 1. When PTV-70 volume
was evaluated concerning D2%, D98% and D50% values, DIMRT,
IMAT and HT techniques were found to be significantly
more optimal than the 3D-CRT technique.
There was no significant difference between intensitymodulated
techniques (p>0.05). Between IMAT and
HT techniques, significantly differences were observed
for D%2 of PTV-63. The IMAT was superior to the HT.
No significant differences were found between IMAT
vs. D-IMRT and D-IMRT vs. HT. There was no statistically
significant difference between D98% for PTV-63
volumes of 4 techniques (p>0.05).
In the comparison of HI and CI, three intensitymodulated
modalities (D-IMRT, IMAT, HT) were found to be statistically more optimal than 3D-CRT
and HI index of D-IMRT, IMAT and HT were found
as 0.059, 0.055 and 0.054, respectively. The lowest HI
was obtained by HT. The nearest result to the desired
CI value was obtained with the IMAT, and the worst
was with 3D-CRT. The maximum Monitor Unit (MU)
value was with HT (2181±260) against LINAC-based
modalities (3D-CRT, D-IMRT, IMAT). The minimum
MU was with IMAT.
Evaluation of OAR Doses Parameters
The statistical comparison of the critical organ values
[Dose Maximum (Dmax), Mean (Dmean) and Dose
volumes (VGy%)] obtain by four different technique is
given in Table 2.
The average Dmax (Gy) values of the spinal cord were
significantly lower with the 3D-CRT technique compared
to D-IMRT, IMAT and HT techniques. Although
there was no statistically significant difference between
D-IMRT, IMAT and HT techniques, better values were
provided with the D-IMRT technique.
The evaluation of Dmean (Gy), Dmax (Gy) and volumebased
criteria (V35%, V50% and V63%) values for the right
and left carotid arteries showed that three different
intensity modalities were statistically significantly superior
to 3D-CRT in dose sparing of the carotid arteries.
No statistically significant differences were found
between the IMRT techniques in the comparison of
carotid artery dose values. The lowest Dmean (Gy) values
were obtained with HT for bilateral carotid arteries.
The results found in the evaluation of Dmean (Gy) of
submandibular glands were similar to carotid arteries.
While IMRT techniques provide statistically significantly
superiority compared to 3D-CRT, no statistically
differences were found among the IMRT techniques.
Looking at the average Dmean (Gy), IMAT yielded
smaller dose values than D-IMRT and HT. When the
thyroid gland doses were evaluated, the IMRT techniques
exhibited statistically significantly superiority
to 3D-CRT concerning the average Dmean (Gy), V30%
and V50%. The average Dmean (Gy) dose values to the thyroid
glands were 29.28, 20.16, 18.31 and 20.54 Gy for
3D-CRT, D-IMRT, IMAT and HT plans, respectively.
There was no statistically significant difference among
the IMRT techniques. Similar results were observed
when volume-based criteria (V30% and V50%) were examined.
IMAT provided superior values compared to
D-IMRT and HT for sparing the thyroid gland.
The average mean dose values of the Pharyngeal
Constrictor Muscles (PCM) were 32.76, 30.38, 29.33,
and 29.49 Gy for 3D-CRT, D-IMRT, IMAT and HT plans, respectively. Although there was no statistically
significant difference to the results of the comparison
of four techniques, the IMRT techniques have lower
PCM (Gy) values compared to 3D-CRT. The lowest average
values were reached by the IMAT technique.
When the volumes of normal tissue of receiving 5
Gy (V5Gy) were evaluated, the average mean volumes
to 5 Gy were 3.55, 8.35, 8.76 and 9.10 cc for 3D-CRT,
D-IMRT, IMAT and HT, respectively. There were
statistically significant differences among the IMRT
techniques. The 3D-CRT plans compared to intensity-
modulated techniques (D-IMRT, IMAT, HT) had a
lower average V5Gy.
Discussion
In the treatment of EGL cancer, high cure rates can be
obtained with both surgery and radiotherapy. Although
these treatment modalities offer similar treatment outcomes,
many factors, such as the location of the tumor,
the degree of the disease, the physician and patient's
choice, are important in the choice of the modality.[]
With radiotherapy, the 5-year local control is at >90%
and 80% for T1 and T2 disease, respectively.[] The controversy
continues between the modalities of surgery
and radiotherapy in the treatment of EGL cancer, while
the researches on the dose/fractions schemes, treatment
contouring and techniques in the radiotherapy
of EGL also continue. Several institutions use different
dose/fraction schemes with different radiotherapy techniques.
While EGL cancer can be treated using standard
dose/fractions schemes daily 2 Gy dose total 66-70 Gy,
there are studies on hypo-fraction schemes (2.25x28=63
Gy) and stereotactic dose fraction schemes (4.50x10=45
Gy), including our institute.[20,21] A few studies have
indicated that local control is more optimal with higher
doses per fraction, specifically when ≥2.25 Gy per fraction
is used.[] Radiation therapy has been delivered
using lateral-opposed field, low energy photon fields
that cover the whole larynx. The parallel-opposed fields
(2D-RT and 3D-CRT) are used and given high survival
rates in EGL radiotherapy before the advancement of
radiotherapy techniques. Some authors have suggested
that conventional lateral opposed fields RT for EGL
cancer should be avoided because conventional lateral
technique increases the dose of carotid arteries. IMRT
based techniques decrease dose to the nearby critical
structures of target volüme.[]
In this work, we compared four different RT modalities
for EGL cancer of 15 patients who were treated before.
Our goal was to determine the capability of each modality, how to provide PTV coverage and evaluate
the data of critical organ doses.
As shown in Table 1, our data suggest that three
different IMRT techniques (D-IMRT, IMAT, HT) better
than 3D-CRT concerning PTV doses, HI and CI.
These IMRT techniques (D-IMRT, IMAT, HT) show
similar results about PTV doses, CI and HI values. HT
had much more MU than other techniques. High MU
values are suspected to increase the risk of secondary
cancer since the volume of normal tissue receiving low
doses increased due to scattering and leakage caused
by scattering leaf intervals in the IMRT techniques. The
minimum MU values were achieved with the IMAT
technique. A reduction in beam-on time may reduce
radiation failure stemmed from organ and patient"s
movements.[]
The stroke can be seen as the most important toxicity
in EGL radiotherapy. Several studies show that irradiation
of neck increases the paralysis incidence and
cerebrovascular diseases.[,] Dorresteijn et al.[]
reported that ischemic paralysis risk after radiotherapy
of the neck was 10 times greater than the general
population under 60 years old. We determined that the
carotid dose is lower in three IMRT techniques than a
3D-CRT technique for EGL cancer. Many studies have
suggested the use of a dangerous dose-response value
instead of a carotid artery threshold dose. Martin et
al.[] suggested that thickness intima-media was statistically
significant for the dose ?35-50 Gy. As shown
in Table 2, in this work, the most suitable V35% and V50%
values were obtained from three different IMRT techniques
compared to 3D-CRT. These values in our study
were determined higher than literature values. This
may be due to the higher PTV volumes and higher
treatment dose in our study.
In the study, IMAT plans had the lowest V30%, V50%
and the lowest mean dose for the thyroid glands. The
IMRT techniques had lower thyroid gland doses than
3D-CRT. It has been shown that head and neck cancer
radiotherapy causes side effects, such as hypothyroidism,
hyperthyroidism, Graves" disease and thyroid
malignancies on thyroid glands.[] It has been
reported that 25 to 50% of patients undergoing head
and neck radiotherapy have some reduction in thyroid
function and 6 to 15% have hypothyroidism.[] The
dose given to the thyroid gland has critical importance
in EGL cancer radiotherapy. IMRT techniques may
provide a clinical benefit in lowering the adverse effects
of thyroid function because of the capability of delivering
a lower dose to the thyroid than the 3D-CRT.[]
Submandibular glands are another significant organ near PTV. When evaluated concerning dose-response,
Murdoch-Kinch et al. show that submandibular gland?
stimulated salivary function decreased remarkably
after a mean dose of >40 Gy. In this work, the IMRT
techniques were provided much more sparing than
3D-CRT in left-right submandibular glands with lower
Dmean doses.
In conventional fractionation treatments, the tolerance
dose for the spinal cord is about 50 Gy.[]
Spinal cord doses above 60 Gy can cause very serious
side effects known as chronic progressive radiation
myelopathy.[,] Our results indicate that 3D-CRT
has lower spinal cord Dmax doses than the IMRT techniques.
Although there was no statistically significant
difference among the 3 IMRT techniques, some values
obtained by the D-IMRT technique were better. The
technique that keeps the spinal cord doses at the lowest
level is the 3D-CRT. The use of the 3D-CRT technique
can be considered in cases for whom a low dose of the
spinal cord is desired in re-irradiation.
Radiotherapy for head and neck cancer may cause
increased side-effects, including dysphagia and aspiration.
Feng et al.,[] in a study of the pharyngeal constrictors
of the average dose (Dmean) <60 Gy, if the limit
is below this to no patients have suggested that no aspiration.
Based on the videofluoroscopy findings, Eisbruch
et al.[] suggested that the average dose of PCM
was significantly associated with the occurrence of late
dysphagia and aspiration at doses >50 Gy. The average
mean dose values to the PCM were 32.76, 30.38, 29.33,
and 29.49 Gy for 3D-CRT, D-IMRT, IMAT and HT
plans, respectively. Although there was no statistically
significant difference to the results of comparison of 4
techniques, D-IMRT, IMAT and HT techniques have
lower PCM Dmean (Gy) values compared to 3D-CRT.
Low-dose on healthy tissue outside the treatment
area is particularly important for radiation-induced
secondary cancers. An important concern for IMRT
techniques is that low doses of radiation increase the
scattering over normal tissue volume and potentially
increase the risk of secondary cancer. It is estimated
that the incidence of secondary cancers can be almost
doubled with IMRT techniques compared to conventional
techniques.[] When the volumes of normal
tissue of receiving 5 Gy (V5Gy) were evaluated, 3D-CRT
plans compared to the IMRT techniques had a lower
average of V5Gy. Although no statistically significant
differences were found among the IMRT techniques,
Helical Tomotherapy (HT) plans had more V5Gy than
other IMRT techniques.
When using a 63 Gy treatment dose by Ekici et al.,[] HT treatment planning has been shown to be
the most effective method for lowest right carotid, left
carotid, submandibular and thyroid doses. In our study,
where we prescript a 70 Gy dose to PTV, we found that
HT treatment planning was the most effective method
for the lowest right carotid, left parotid, submandibular
and thyroid doses. On the other hand, we found
that IMAT planning provided the lowest right and left
submandibular (V5Gy), thyroid (V5Gy) and PCM (V5Gy)
doses. The results of our study suggest that HT and
IMAT planning are the most appropriate methods to
increase the treatment dose from 63 Gy to 70 Gy.
Conclusion
The findings obtained in this study suggest that it is
possible to administer a treatment dose of 70 Gy to the
PTV of EGL with all planning techniques used in this
work. However, it is observed that there are advantages
or disadvantages among each other. Based on the dosimetric
findings in this study, D-IMRT, IMAT and HT
treatment plans that were created using the SIB technique
were superior to the 3D-CRT plans created using
conventional boost technique concerning the PTV (coverage),
CI and HI values of the treatment volumes. With
the 3D-CRT technique, it is difficult to achieve sharp
dose drops in treatment volumes with overlapping PTV.
However, this technique that keeps the spinal cord doses
at the lowest level is. The use of the 3D-CRT technique
can be considered in organs where low doses preferred
to where complications of re-radiotherapy should be
taken account in advance, such as spinal cord. Three different
IMRT techniques provided superiority with less
variation among themselves compared to 3D-CRT plans
concerning carotid artery, thyroid gland, submandibular
glands and PCM doses. IMAT and 3D-CRT techniques
yielded minimum MU values compared to other techniques.
On the other hand, in the case of normal tissue
doses, which are important for secondary cancers, the
3D-CRT technique is superior to the IMRT techniques.
We recommend to increase the treatment dose
from 63 Gy to 70 Gy in the radiotherapy of EGL cancer
but to select the technique according to the patient"s
condition. Patient age, treatment volumes, and critical
organ protection should be taken into consideration
for patient-specific decision-making.
Peer-review: Externally peer-reviewed.
Conflict of Interest: The authors declare that they have no
conflict of interest.
Ethics Committee Approval: This study was conducted in
accordance with local ethical rules. (Date: 01.12.2017, Registration
number: 2017/1399)
Financial Support: This work has no funding source.
Authorship contributions: Concept - M.O., B.Ş.; Design
- M.O., B.Ş.; Supervision - M.O., M.A.; Funding - M.O.,
B.Ş., C.K., K.Ö.T., M.A.; Materials - M.O., B.Ş., C.K., K.Ö.T.,
M.A.; Data collection and/or processing - M.O., B.Ş., C.K.;
Data analysis and/or interpretation - M.O., B.Ş., B.D.; Literature
search - B.Ş., M.O.; Writing - M.O., B.Ş., B.D.; Critical
review - M.O., K.Ö.T., B.D., M.A.
References
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent
J, Jemal A. Global cancer statistics, 2012. CA Cancer J
Clin 2015;65(2):87-108.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin
DM. Estimates of worldwide burden of cancer in 2008:
GLOBOCAN 2008. Int J Cancer 2010;127(12):2893-
917.
Niederhuber JE, Armitage JO, Doroshow JH, Kastan
MB, Tepper JE. Abeloff"s. Clinical Oncology. 5th ed.
Elsevier Inc; 2013.
Higgins KM, Shah MD, Ogaick MJ, Enepekides D.
Treatment of early-stage glottic cancer: meta-analysis
comparison of laser excision versus radiotherapy. J
Otolaryngol Head Neck Surg 2009;38(6):603-12.
Halperin EC, Brady LW, Wazer DE, Perez CA. Perez
and Brady"s principles and practice of radiation oncology.
6th ed. Philadelphia: Wolters Kluwer Health/
Lippincott Williams & Wilkins; 2013.
Zumsteg ZS, Riaz N, Jaffery S, Hu M, Gelblum D, Zhou
Y, et al. Carotid sparing intensity-modulated radiation
therapy achieves comparable locoregional control to
conventional radiotherapy in T1-2N0 laryngeal carcinoma.
Oral Oncol 2015;51(7):716-23.
Fujita M, Rudoltz MS, Canady DJ, Patel P, Machtay
M, Pittard MQ, et al. Second malignant neoplasia in
patients with T1 glottic cancer treated with radiation.
Laryngoscope 1998;108(12):1853-5.
Mendenhall WM, Werning JW, Hinerman RW, Amdur
RJ, Villaret DB. Management of T1-T2 glottic carcinomas.
Cancer 2004;100(9):1786-92.
Rosier JF, Grégoire V, Counoy H, Octave-Prignot M,
Rombaut P, Scalliet P, et al. Comparison of external
radiotherapy, laser microsurgery and partial laryngectomy
for the treatment of T1N0M0 glottic carcinomas:
a retrospective evaluation. Radiother Oncol
1998;48(2):175-83.
Dorresteijn LD, Kappelle AC, Boogerd W, Klokman
WJ, Balm AJ, Keus RB, et al. Increased risk of ischemic stroke after radiotherapy on the neck in patients
younger than 60 years. J Clin Oncol 2002;20(1):282-8.
Smith GL, Smith BD, Buchholz TA, Giordano SH,
Garden AS, Woodward WA, et al. Cerebrovascular
disease risk in older head and neck cancer patients
after radiotherapy. J Clin Oncol 2008;26(31):5119-25.
Tell R, Sjödin H, Lundell G, Lewin F, Lewensohn
R. Hypothyroidism after external radiotherapy for
head and neck cancer. Int J Radiat Oncol Biol Phys
1997;39(2):303-8.
Murdoch-Kinch CA, Kim HM, Vineberg KA, Ship
JA, Eisbruch A. Dose-effect relationships for the submandibular
salivary glands and implications for their
sparing by intensity modulated radiotherapy. Int J Radiat
Oncol Biol Phys 2008;72(2):373-82.
Kirkpatrick JP, van der Kogel AJ, Schultheiss TE. Radiation
dose-volume effects in the spinal cord. Int J Radiat
Oncol Biol Phys 2010;76(3 Suppl):S42-S9.
Rosenthal DI, Fuller CD, Barker JL Jr, Mason B, Garcia
JA, Lewin JS, et al. Simple carotid-sparing intensitymodulated
radiotherapy technique and preliminary
experience for T1-2 glottic cancer. Int J Radiat Oncol
Biol Phys 2010;77(2):455-61.
Hall EJ, Wuu CS. Radiation-induced second cancers:
the impact of 3D-CRT and IMRT. Int J Radiat Oncol
Biol Phys 2003;56(1):83-8.
Ekici K, Pepele EK, Yaprak B, Temelli O, Eraslan AF,
Kucuk N, et al. Dosimetric comparison of helical tomotherapy,
intensity-modulated radiation therapy,
volumetric-modulated arc therapy, and 3-dimensional
conformal therapy for the treatment of T1N0 glottic
cancer. Med Dosim. 2016;41(4):329-33.
Prescribing, Recording, and Reporting Photon-Beam
Intensity-Modulated Radiation Therapy (IMRT):
ICRU Report No: 83, J ICRU 2010;10(1). Available at:
https://academic.oup.com/jicru/article-abstract/10/1/
NP/910527?redirectedFrom=fulltext. Accessed Mar
17, 2020.
Gomez D, Cahlon O, Mechalakos J, Lee N. An investigation
of intensity-modulated radiation therapy versus
conventional two-dimensional and 3D-conformal
radiation therapy for early stage larynx cancer. Radiat
Oncol 2010;5:74.
Ding C, Chun SG, Sumer BD, Nedzi LA, Abdulrahman
RE, Yordy JS, et al. Phantom-to-clinic development
of hypofractionated stereotactic body radiotherapy
for early-stage glottic laryngeal cancer. Med
Dosim 2017;42(2):90-6.
Yamazaki H, Nishiyama K, Tanaka E, Koizumi M,
Chatani M. Radiotherapy for early glottic carcinoma
(T1N0M0): results of prospective randomized study of
radiation fraction size and overall treatment time. Int J
Radiat Oncol Biol Phys 2006;64(1):77-82.
Martin JD, Buckley AR, Graeb D, Walman B, Salvian
A, Hay JH. Carotid artery stenosis in asymptomatic
patients who have received unilateral head-
-and-neck irradiation. Int J Radiat Oncol Biol Phys
2005;63(4):1197-205.
Garcia-Serra A, Amdur RJ, Morris CG, Mazzaferri E,
Mendenhall WM. Thyroid function should be monitored
following radiotherapy to the low neck. Am J
Clin Oncol 2005;28(3):255-8.
Matthiesen C, Herman Tde L, Singh H, Mascia A, Confer
M, Simpson H, et al. Dosimetric and radiobiologic
comparison of 3D conformal, IMRT, VMAT and proton
therapy for the treatment of early-stage glottic cancer.
J Med Imaging Radiat Oncol 2015;59(2):221-8.
Emami B, Lyman J, Brown A, Coia L, Goitein M,
Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys
1991;21(1):109-22.
Esik O, Csere T, Stefanits K, Szakáll S Jr, Lengyel Z,
Sáfrány G, et al. Increased metabolic activity in the
spinal cord of patients with long-standing Lhermitte"s
sign. Strahlenther Onkol 2003;179(10):690-3.
Feng FY, Kim HM, Lyden TH, Haxer MJ, Feng M,
Worden FP, et al. Intensity-modulated radiotherapy of
head and neck cancer aiming to reduce dysphagia: early
dose-effect relationships for the swallowing structures.
Int J Radiat Oncol Biol Phys 2007;68(5):1289-98.
Eisbruch A, Lyden T, Bradford CR, Dawson LA, Haxer
MJ, Miller AE, et al. Objective assessment of swallowing
dysfunction and aspiration after radiation concurrent
with chemotherapy for head-and-neck cancer. Int
J Radiat Oncol Biol Phys 2002;53(1):23-8.
