A Phase II Investigation of Contralateral Arytenoid Sparing IMRT for T1a and T2a Larynx Cancer With Detailed Analysis of Post-treatment Laryngeal Function
Phase: PHASE2
Conditions: Laryngeal Neoplasms
Sponsor: Fox Chase Cancer Center

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RT-083 A phase II investigation of contralateral arytenoid sparing IMRT for T1a and T2a 
larynx cancer with detailed analysis of post-treatment laryngeal function
Supported by: Department of Radiation Oncology
Principal Investigator:
Thomas Galloway MD
Fox Chase Cancer Center
333 Cottman Avenue
Philadelphia PA, 19111
Phone: 215-728-5536
Fax: 215-214-1629
Email: thomas.galloway@fccc.edu
Co-Investigators:
Nausheen Jamal MD
Fox Chase Cancer Center
333 Cottman Avenue
Philadelphia PA, 19111
Phone: 215-214-7873
Fax: 215-214-1629
Email: nausheen.jamal@fccc.edu
Barbara Ebersole MA, CCC-SLP
Fox Chase Cancer Center
333 Cottman Avenue
Philadelphia PA, 19111
Phone: 215-728-0568
Email: barbara.ebersole@fccc.edu
Statistician:
Elizabeth Handorf PhD 
Fox Chase Cancer Center
Department of Biostatistics
333 Cottman Avenue
Philadelphia PA, 19111
Phone: 215-728-4773
Email: elizabeth.handorf@fccc.edu
Version Date: 06/20/2015 
Amendment 1: 09/19/2015

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Amendment 2: 02/07/2017
Amendment 3: 07/31/2017
Table of Contents
Table of Contents
2
1.0 Introduction
4
1.1
Study Rationale
4
2.0 Objectives
7
2.1 Primary Objective
7
2.2 Secondary Objectives
7
3.0 Study Plan
8
3.1 Description of Study Design, Population and Duration of Study Therapy
8
4.0 Patient Selection Inclusion & Exclusion
9
4.1 Inclusion Criteria
9
4.2 Exclusion Criteria
9
4.3 Inclusion of Women and Minorities
10
4.4 Pregnancy
10
4.5 Patient Registration
11
5.0 Treatment Plan
11
5.1 Targets
11
5.2 Volume and ICRU Reference Point Definitions
10
5.3 Targets and Critical Normal Tissue Definitions
11
5.4 Planning
12
5.5 External beam equipment and beam delivery methods
13
5.6 Daily Treatment Localization/IGRT
13
5.7 Concomitant Medications, Supportive Care, Excluded Therapies and Restrictions
16
5.8 Duration of Therapy
16
5.9 Duration of Follow up
16
5.10 Criteria for Discontinuation
16
6.0 Risks to Participants
17
7.0 Potential Benefits to Participants
17
8.0 Cost to Participants
17
9.0 Study Calendar
18
10.0 Adverse Events
19

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10.1 Definitions
19
10.2 Recording and Reporting Responsibilities
20
10.3 Pregnancy
22
11.0 Statistical Analysis
23
12.0 Data and Safety Monitoring Plan
23
12.1 Monitoring Plan
24
12.2 Data Safety Monitoring Committee
24
13.0 Administrative
24
13.1 Data Reporting
25
13.2 Retention of Records
25
13.3 Informed Consent
25
14.0
References
26
Eating Assessment Tool – 10 (EAT-10)
28

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1.0 Introduction
Parallel opposed portal external beam radiation is the standard nonsurgical treatment 
for T1-2N0 glottic cancer.1  This technique involves treatment of the entire larynx for 
tumors that are small and limited.  Although technological advances now allow 
radiation oncologists selectively to target and avoid adjacent sub-portions of any 
organ, these tools have not been applied T1-2N0 glottic cancer due to the perceived 
low toxicity of standard therapy.  However, radiotherapy for early glottic cancer is 
not without functional side effects 2 and it is not known whether post-treatment 
function after whole larynx radiation is superior to a more targeted surgical approach3 
This is a phase II study to treat unilateral glottic cancer (Stage T1a and T2aN0) with 
intensity modulated radiation therapy (IMRT).  In view of the anticipated small 
volume of disease at presentation and need to limit the potential for a “marginal 
miss”, treatment will include the entire involved vocal fold, anterior commissure, and 
the anterior 1/3 of the contralateral vocal fold thus sparing the contralateral arytenoid 
cartilage and musculature (“contralateral arytenoid sparing IMRT”).   In addition, we 
propose to perform sophisticated objective and patient reported measures regarding 
speech outcomes for two years after the completion of therapy at specified intervals, 
to better gain an understanding of the effects of therapy.  Our findings will have the 
potential to dramatically advance the field of early larynx cancer therapy by 
demonstrating the efficacy of limiting the volume of uninvolved larynx that receives 
radiation and comprehensively assessing the functional outcomes of said therapy.
1.1 Study Rationale 
T1-2N0 glottic squamous cell carcinoma (SCC) is traditionally treated with 
simple, parallel opposed radiation fields 4 with a gratifying control rate 1,5-7.  
Although the technological sophistication of the administration of external 
beam radiation has increased dramatically in the past 50 years, treatment of 
early stage larynx cancer has changed little since 1964 5.  The reason for this 
is twofold: the efficacy of radiation therapy prescribed in this manner and the 
perceived low toxicity of treatment.  
The favorable toxicity profile of parallel opposed radiation for early glottic 
tumors is largely a result of the low incidence of nodal metastases 8, 
permitting omission of elective nodal irradiation from treatment plans.  Thus, 
most radiosensitive normal tissues9 are clear of the radiation field.  Large 
single-institution retrospective experiences of both primary radiation 5,10 and 
transoral surgery 8 report long term serious complications on the order of 1%.  
Randomized trials of primary radiation 6,7,11 report higher rates of long term 
toxicity, approaching 10%, perhaps due to more careful prospective reporting.   
The combination of low long term toxicity and excellent efficacy is appealing, 
however early larynx tumors are typically quite small 8 and parallel opposed 
radiotherapy results in treatment of the entire larynx, complicating salvage 
operations when necessary .  Typical head and neck radiation assessments of 
toxicity 12 may not be applicable.

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The excellent treatment outcomes of early larynx cancer and its incidence 13 
(which may be rising) suggest that survivorship concerns merit greater 
consideration than previously afforded in the reported experiences.  One facet 
of head and neck cancer survivorship that can uniquely be addressed in early 
larynx cancer is radiation dose to the carotid arteries, because elective 
lymphatic radiation is not required.  External beam radiotherapy is an 
independent risk factor for accelerating carotid atherogenesis 14; head and 
neck cancer patients treated with radiation have been demonstrated in some 
data sets to have an increased risk of ischemic stroke 15,16. In parallel opposed 
radiation, the carotid arteries generally receive a dose of radiation similar to 
that of the tumor (Figure 2).   By contrast, they can be significantly avoided 
without compromising target coverage through IMRT, and pilot studies have 
demonstrated encouraging results with this technique 17.
However, it is difficult to assess the benefit of ‘carotid artery avoidance 
IMRT’.  It is impossible to spare the artery completely 18 and it is unknown 
whether the development of a cerebrovascular event is dose-dependent.  In 
addition, the median time to an occurrence is roughly 10 years 15 after the 
completion of radiation, making any current determination of the efficacy of 
the change impossible.  By contrast, determining the benefit of “contralateral 
arytenoid sparing IMRT” does not suffer from such limitations.  Dose-volume 
relationships in the development of head and neck radiation toxicity are well 
described for advanced head and neck tumors 19 and it is reasonable to expect 
that similar dose volume parameters can be defined for early larynx cancer.  
The assessment of toxicity for early glottic cancer must focus on vocal quality 
and deglutition. 
Any new application of highly conformal intensity modulated radiotherapy 
must account for organ motion during treatment (intrafraction uncertainty) 
and setup error (interfraction uncertainty).  For the larynx, organ motion will 
be expected to be secondary to respiration.  Although it is intuitive that the 
larynx moves with respiration, the movement relative to the contralateral cord 
is relatively minimal in early larynx cancer patients.  A 4DCT analysis 
demonstrated that internal vocal cord motion is approximately 1 mm in all 
measured planes, suggesting that single vocal cord irradiation would not be 
hampered by respiratory motion20.  To correct for daily setup uncertainty, 
daily CBCT registration and correction reduces random positioning errors to 
less than 1 mm21.  Despite these small displacements, the uncertainty of single 
vocal cord IMRT combined with the success of conventional treatment 
demands caution.  Using proposed contouring expansions (section 5.2.3) the 
following normal tissue goals were obtained on the 5 most recent 
TIS/T1a/T2a patients treated at FCCC:

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Contralateral 
Aretynoid
Ipsilateral Carotid 
Artery
Contralateral 
Carotid Artery
Inferior Pharyngeal 
Constrictor
Esophageal Verge
Spinal Cord
1
21.36
53.3
4.7
43.2
54
16.8
2
16.9
32.3
7.5
38
34
20
3
33.3
39
4
35
28
14
4
12
46.5
6
50
33.7
22
5
20.5
29
12.4
43.1
20.5
9
MEAN
20.81
40.02
6.92
41.86
34.04
16.36
1All doses listed in Gy
2All dose listed are mean dose to organ except spinal cord (maximum dose to 
a point)
In this planning exercise, reducing dose to the spinal cord well below the 
standard dose of 45 Gy was prioritized because 1.) standard parallel opposed 
radiation delivers negligible dose to the spinal cord and 2.) second tumors in 
this population are not uncommon22 and diagnosis of such may require an 
additional course of head and neck radiation which would be complicated by 
unnecessary dose to the spinal cord.
Many recent studies have attempted to document the voice outcomes 
following treatment of early glottic carcinomas2,3,20-26.  Using many different 
instruments, these analyses suggest that regardless of treatment modality and 
radiation fractionation, some voice dysfunction is common after treatment.  In 
view of the high cure rates associated with this disease, the functional 
outcomes of each modality become especially important. Clinician awareness 
and patient education regarding potential side effects and declines in voice 
and/or swallow function can help guide the decision-making process. Thus, 
the functional outcomes of early glottic cancer patients undergoing treatment 
with IMRT are of substantial importance as well.
The above referenced studies document voice changes based both upon 
perception of clinicians and patients. The present study will incorporate the 
most commonly used tools employed in these studies. Objective clinician 
analysis most commonly includes use of a validated, perceptual scale, such as 
the GRBAS scale (APPENDIX) 27. In this scale, each of the named vocal 
characteristics is assigned a score of 0 to 3, where 0 represents normal and 3 
represents severe. This is done by experienced listeners (in this study, two 
speech and language pathologists and a laryngologist). Typical objective 
measures include measurements of fundamental phonation frequency (F0, 
measured in Hz), maximal phonation times (MPT, measured in seconds), jitter 
(percent frequency perturbation), shimmer (percent amplitude perturbation), 
and noise-to-harmonic ratio (NHR). These measurements are performed using 
electro-acoustic analysis of a recorded voice sample. Further objective 
analysis will be performed using laryngovideostroboscopy. This is performed 
using a transnasal or transoral endoscope, which records vocal fold movement 

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and vibration using a strobe light source. These recordings will then be 
evaluated for amplitude, symmetry, and periodicity of the vocal fold mucosal 
wave; presence or absence of glottic closure; and degree of mobility by 
measuring the angle of abduction of each vocal fold from the midline. The 
most widely used subjective patient perception tool is the VHI, which is a 
validated, self-administered 30 item questionnaire covering three domains: 
functional, physical, and emotional (APPENDIX) 28. This questionnaire will 
be administered at each visit and takes less than 10 minutes to complete. 
Deglutition changes following treatment of early glottic carcinomas with 
radiation are not well-studied. Peretti et al. reviewed swallow outcomes 
following transoral laser surgery for T2-T3 cancers, and found that up to 4% 
of patients develop aspiration with high patient-perceived difficulty with 
swallowing23. Another study reviewed quality of life concerns in patients who 
had undergone endoscopic laser resection of T1-T2 cancers, and found that 
two issues of highest concern to recovering patients were salivary 
production/control and swallowing29. Similar data are unavailable for patients 
undergoing radiation therapy. 
The proposed study will therefore include objective and subjective measures 
of swallow function. Objective evaluation will be employed using the 
Penetration-Aspiration Scale as well as the Functional Outcome of 
Swallowing Scale 30,31. Subjective evaluation will be performed using the 
validated EAT-10, which is a 10 item self-administered questionnaire that 
takes 1-2 minutes to complete 32
2.0 Objectives 
To define a new treatment technique for T1a larynx cancer that maintains excellent 
local control with less extensive radiation fields
Hypothesis: Contralateral arytenoid sparing IMRT for T1a larynx cancer maintains 
the excellent local control associated with whole larynx radiation and results in 
functional outcomes at 24 months after therapy that are suggestive of improved 
function when compared to historical controls
2.1 Primary Objectives and Endpoints
Voice quality outcomes at 24 months after contralateral arytenoid sparing 
IMRT for T1a/T2a larynx cancer
Two year local control with contralateral arytenoid sparing IMRT for T1a/T2a 
larynx cancer

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2.2 Endpoints 
2.1.1
Primary endpoint
Demonstrate a 50% improvement in the VHI (voice handicap index) score 
at 24 months after the completion of therapy
2.2.2 Secondary Endpoints
Demonstrate a similar 2-yr local control of (>85%) with IMRT therapy for 
T1a and T2aN0 larynx cancer
Evaluate clinician-reported voice quality at defined intervals up to 24 
months after the completion of radiation using the Grade, Roughness, 
Breathiness, Asthenia, and Strain (GRBAS) scale
Use the Eating Assessment Tool (EAT-10) to evaluate patient-reported 
satisfaction with swallowing at up to 24 months after the completion of 
radiation
Evaluate clinician-reported measures of swallowing 24 months after the 
completion of radiation as measured by fiberoptic endoscopic evaluation 
of swallowing (FEES) using the penetration, aspiration scale (PAS) scores 
for 3 commonly evaluated textures (cookie, puree, thin). 
2.3 Purpose/Specific Aim of this Research Study: To define a new treatment technique 
for T1a larynx cancer that maintains excellent local control with less extensive 
radiation fields
2.4 Hypothesis: Contralateral arytenoid sparing IMRT for T1a larynx cancer maintains 
the excellent local control associated with whole larynx radiation and results in 
functional outcomes at 24 months after therapy that are suggestive of improved 
function when compared to historical controls
3.0 Study Plan 
3.1 Description of Study Design, Population and Duration of Study Therapy 
This is a single arm phase II study.  All subjects will be treated with the standard 
fractionation for T1a glottic cancer at FCCC: 63 Gy in 28 fractions6 for T1a and 
65.25 Gy in 29 fractions33 for T2a.  

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Subjects will be patients referred to FCCC or Temple for treatment of T1 glottic 
cancer.  Patients will be approached for trial accrual during the pretreatment 
process.  Patients will be provided with the informed consent document to educate 
themselves regarding the rationale of the study. Patients with T1a larynx cancer 
that agree to the functional assessment of the study will be identified as potential 
candidates. The duration of protocol assessment is 24 months.
Subjects will be seen in follow-up at least every 3 months for the first year and 
every 4 months for the second year after therapy for tumor surveillance, 
consistent with the standard of care.  
Subjects will also be seen by speech therapy on a separate schedule, consistent 
with current institutional practice of voice rehabilitation after this therapy.  At the 
1,3,6,12, and 24 months follow-up patient reported questionnaires and functional 
assessments will be captured and recorded
Number of 
subjects per 
year projected 
at 
FCCC/Temple
Total number of 
subjects at 
FCCC/Temple
Number of subjects 
nationally or 
internationally (if 
applicable
Number of 
subjects at 
collaborating 
institutions (if 
applicable)
Up to: 4
Up to: 30
0
0
4.0 Patient Selection Inclusion & Exclusion
4.1 Inclusion Criteria  
4.1.1 Patients with histologically proven invasive squamous cell carcinoma 
arising from the true vocal cord.
4.1.2 T1a and T2a squamous cell carcinoma of the glottic larynx (tumor 
limited to one vocal cord with normal cord mobility).
4.1.3 Squamous cell carcinoma in-situ of a single vocal cord (Tis) is eligible.
4.1.4 Minimum age of entry is 18 years.
4.1.5 Patients must be able to read and write English to comply with the 
questionnaire portions of the protocol.
4.1.6 ECOG performance status of 0 or 1.
4.2 Exclusion Criteria  
4.2.1 Patients with verrucous or adenocarcinoma

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4.2.2 Patients with T1 tumors on both cords (T1b)
4.2.3 Patients with T2b-T4 true larynx tumors
4.2.4 Patients with primary supraglottic tumors that involve the true larynx
4.2.5 Patients with a prior or concurrent malignancy (other than non-
melanoma skin cancer or carcinoma in-situ of the cervix) are ineligible 
unless the previous cancer was treated 5 years or more prior to the 
current tumor and the patient has remained continually disease free
4.2.6 Prior radiation to the head and neck
4.2.7 Pregnant or breastfeeding. A negative blood-pregnancy test is required 
for women of childbearing potential (WOCBP) within 14 days prior to 
her CT stimulation for treatment planning. Refer to section 4.4 for 
further detail.
4.3 Inclusion of Women and Minorities
Men and women, regardless of race, ethnic group or sexual orientation are 
eligible for this study.  
4.4 Pregnancy
The effects of radiation therapy on the developing human fetus at the 
recommended therapeutic dose are known to be teratogenic.  For this reason 
women of child-bearing potential (WOCBP) and men must agree to use 
adequate contraception (hormonal or barrier method of birth control; 
abstinence) prior to study entry, for the duration of treatment.  Should a 
woman become pregnant or suspect she is pregnant while participating in this 
study, she must inform her treating physician immediately.
Prior to study enrollment, WOBCP must be advised of the importance of 
avoiding pregnancy during trial participation and the potential risk factors for 
an unintentional pregnancy.  In additional, men enrolled on this study should 
understand the risks to any sexual partner of childbearing potential.
All WOCBP must have a negative pregnancy test within 14 days prior to CT 
stimulationfor treatment planning.  If the pregnancy test is positive, the patient 
must not receive the CT nor protocol treatment and must not be enrolled in the 
study.
WOCBP is defined as follows: Any female who has experienced menarche 
and who has not undergone successful surgical sterilization (hysterectomy, 
bilateral tubal ligation, or a bilateral oophorectomy) or is not postmenopausal 
(defined as amenorrhea > 12 consecutive months, or women on hormone 

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replacement therapy (HRT) with documented plasma follicle-stimulating 
hormone (FSH) level > 35 mIU/ml).  Even women who are using oral, 
implanted, or injectable contraceptive hormones or mechanical products 
(diaphragm, condoms, spermicides) to prevent pregnancy or practicing 
abstinence or where partner is sterile (e.g. vasectomy), should be considered 
to be WOCBP.
4.5 Patient Registration
Participants may be registered from 8:00 am to 5:00 pm EST excluding holidays 
by emailing the Investigator-Sponsored Research Unit (ISRU) at: 
FCCC.MONITOR@fccc.edu. Eligible participants will be entered on study 
centrally once the following items have been received by email:

Completed registration form 

Consent and HIPAA signature pages 

Eligibility checklist
Following registration, participants must begin protocol treatment within 14 
calendar days of registration.  Issues that would cause treatment delays must be 
discussed with the Sponsor-Investigator.  If a registered participant does not 
receive protocol therapy following registration, the participant will be recorded as 
withdrawn from study.  The Study Monitor must be notified as soon as possible if 
a participant does not begin protocol treatment as scheduled. For additional 
registration questions, please email FCCC.MONITOR@fccc.edu or call (215) 
728-5544.
The FCCC ISRU will notify the site by email once registration is confirmed and 
the sequence number has been assigned.  Participants must be registered and have 
received a sequence number prior to the initiation of treatment.  
Exceptions to the current registration policies will not be permitted. 
5.0 Treatment Plan
This is a single arm phase II study. All subjects will be treated with the standard 
fractionation for T1a glottic cancer at FCCC/Temple: 63 Gy in 28 fractions6 for T1a 
and 65.25 Gy in 29 fractions33 for T2a as detailed below.
5.1 Targets
5.1.1 The immobilization device must include neck and shoulder 
immobilization.  An aquaplast face mask is required.  The shoulders can 
either be immobilized by a shoulder depression device or an extended 
aquaplast configuration
5.1.2 Treatment planning CT scan in the immobilized position will be 
required to define the tumor, clinical and planning target volume.

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5.1.3 CT thickness must be ≤3mm for the CT simulation.  The CT must 
include the entire larynx
5.1.4 The GTV, CTV, and PTV and normal tissues must be outlined on the 
CT slices in which they exist
5.2 Volume and ICRU Reference Point Definitions
5.2.1 The Gross Tumor Volume (GTV) is defined as all gross disease 
determined from CT, clinical information and endoscopic findings.  T1a 
tumors are small by definition.  There are tumors for which a GTV will 
not be readily available on the CT scan due to small size of the tumor or 
gross tumor extirpation by a biopsy procedure.  For patients where a 
clear GTV is not evident, no GTV volume will be defined
5.2.2 The Clinical Target Volume is defined as the area thought to contain 
gross disease and areas potentially at risk for microscopic disease.  
Regardless of whether a GTV is evident on imaging, the CTV will be 
very simular for every patient
 5.2.2.1 Superior border: Superior extent of the arytenoid cartilage
5.2.2.2 Inferior border: Inferior extent of the true vocal fold
5.2.2.3 Lateral border: Outer aspect of the ipsilateral thyroid 
cartilage
5.2.2.4 Medial border: Air within the larynx at the midline of the 
body
5.2.2.5 Anterior: Volume will completely treat the anterior 
commissure and up to the anterior 1/3 of the contralateral 
vocal fold, in order to minimize the risk of marginal miss
5.2.2.6 Posterior border: Posterior aspect of the arytenoid cartilage. 
Inferiorly, the arytenoid cartilage will not be visible on slices that 
extend to the inferior extent of the true vocal fold.  The posterior 
border in this region should include the ipsilateral portion of the 
cricoid cartilage immediately inferior to the arytenoid and the 
adjacent ipsilateral cricoarytenoid musculature
5.2.3 The Planning Target Volume (PTV) will provide a margin around the 
CTV to compensate for the variabilities of treatment setup and internal 
organ motion.  An asymmetric PTV will be employed due to concerns of 
deglutition preferentially displacing the larynx in the superior/inferio and 
anterior/posterior orientations. Mid-neck anatomy does not allow for a 
10 mm anterior/posterior margin.  Thus 5 mm was chosen  

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5.2.3.1 Superior/inferior PTV expansion: 10 mm
5.2.3.2 Anterior/Posterior 5 mm
5.2.3.3 Meidal/Lateral: 3 mm
5.2.4 After completion of contouring as detailed in 5.2.2 and 5.2.3 the 
superior/inferior extent of the PTV will be measured.  If it measures less 
than 4.0 cm, it will be extended to such a length (the typical treated 
length for standard therapy) by copying and extending the most superior 
and most inferior contour superiorly and inferiorly (respectfully) until a 
4 cm field is achieved.
5.3 Targets and Critical Normal Tissue Definitions
5.3.1 Targets
5.3.1.1
There will be a single target for this protocol – a single 
PTV.  There will be no elective nodal irradiation
5.3.2 Dose
5.3.2.1
Tis and T1a: 63 Gy in 28 fractions T2a: 65.25 Gy in 29 
fractions
5.3.3 Critical Normal Tissue Structures
5.3.4. GSL
5.3.4.1 A secondary volume of GSL – PTV will be createdThis will be 
defined as the glottic and supraglottic larynx, including the tip of the 
epiglottis, the aryepiglottic folds, arytenoids, false cords, and true 
cords, bounded by the thyroid cartilage laterally, anteriorly the anterior 
edge of the pre-epiglottic fat, and posteriorly bounded by the anterior 
edge of the pharyngeal wall or the posterior edge of the arytenoid 
and/or cricoid cartilage.
5.3.5 Contralateral arytenoid
5.3.5.1 The arytenoids are small, 3-sided pyramidal structures that sit 
superior to the cricoid cartilage in the posterior larynx.  They are small 
(mean volume estimated at 0.312 cc).  An attached supplement 
demonstrates 2 contouring examples.  No attempt will be made to 
differentiate the artetynoid and corniculate cartilage  
5.3.6 Ipsilateral carotid artery

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5.3.6.1 Both carotid arteries will be contoured on all slices that include 
a PTV plus 1-2 slices above and below.
5.3.7 Contralateral carotid artery
5.3.8 Spinal Cord
5.3.8.1 The cord will be contoured on all slices that include a PTV plus 
1-2 slices above and below
5.3.9 Inferior pharyngeal constrictor
5.3.9.1 Defined as the pharyngeal musculature beginning at the level of 
the inferior hyoid superiorly and extending to the esophageal verge 
inferiorly.
5.3.10 Esophageal verge
5.3.10.1Extending superiorly from the inferior phyarngeal constrictor 
extending inferiorly to the most inferior level with a PTV contour
5.4 Planning
5.4.1 The treatment for each patient will be inverse planned.  Either step-and-
shoot intensity modulated radiation therapy (IMRT) or volumetric arc 
therapy (VMAT) will be employed. if ste-and-shoot IMRT is employed, 
beams that enter through the contralateral arytenoid should be avoided to 
help with dosimetric goals.
5.4.2 Dose specification
5.4.2.1 95% of the PTV will receive the prescription dose 
5.4.2.2 ≥99.5% of the PTV will receive 95% of the prescription 
dose
5.4.2.3 < 1% of the PTV will receive > 110% of the prescription
5.4.2.4 Prescription will be 63 Gy in 28 fractions (T1a an dTis) or 
65.25 Gy in 29 fractions
5.4.3 Critical Normal Tissue Structures Guidelines 
Spinal cord: < 25 Gy; deviation acceptable <30 Gy
5.4.3.1 Contralateral Arytenoid: Mean Dose ≤ 21 Gy
5.4.3.2 Ipsilateral carotid artery: < 45 Gy
5.4.3.3 Contralateral carotid artery < 10 Gy

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5.4.3.4 Spinal cord: 0.1 cc < 20 Gy
5.4.3.5 Inferior pharyngeal constrictor: Mean Dose < 31.5 Gy
5.4.3.6 Esophageal Verge: < 20 Gy
5.4.4 Doses are prescribed as above.  IMRT prescribing requires 
prioritization.  Prioritization for this investigation is as below:
5.4.4.1 PTV 63
5.4.4.2 Contralateral arytenoids
5.4.4.3 Inferior pharyngeal constrictor
5.4.4.4 Esophageal verge
5.4.4.5 Spinal cord
5.4.4.6 Contralateral carotid artery
5.4.4.7 Ipsilateral carotid artery
5.5 External beam equipment and beam delivery methods
5.5.1 4 or 6 MV beams are required
5.6 Daily Treatment Localization/IGRT
5.6.1 Daily image guidance (IGRT) is required.  This may be achieved 
with the following technique:
5.6.1.1 Linear accelerator mouth kV and MV conebeam CT images
5.6.1.2 CT on rails images
5.6.2 Treatment day procedure to register the imaging dataset are as 
follows:
5.6.2.1 Region of interest (ROI) for fusion is the larynx
5.6.2.2 Both manual and automatic types of registration can be 
used.
5.6.2.3 The result of the fusion must be visually checked for the 
alignment of the cartilages of the larynx (thyroid and 
cricoid cartilage) and the adjacent bony anatomy (cervical 
spine).  

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5.6.2.4 In the instance of a disagreement between cartilage and 
spine alignment, cartilage alignment will be prioritized
5.6.2.5 Following the registration, the translational corrections will 
be applied to the treatment couch.  If one or more 
corrections are larger than 5 mm, imaging must be 
repeated.  
5.6.2.6 Special consideration of first fraction of radiation: If one of 
more corrections are larger than 10 mm, it will be assumed 
that the patient was swallowing during acquisition and the 
image will be repeated.  If the repeat image similarly 
requires a larger than 10 mm, the start of radiation will be 
cancelled for that day.  The same treatment localization will 
then be performed on the next clinic day.  Should a shift 
larger than 10 mm be required again, it will be assumed 
that the patient was swallowing during the CT simulation 
acquisition, introducing a systematic error.  In this 
situation, a new CT simulation and a new treatment plan 
will be required.
5.7 Concomitant Medications, Supportive Care, Excluded Therapies and 
Restrictions
Patients should receive full supportive care therapies concomitantly during the 
study when appropriate. Any disease progression requiring other forms of 
specific anti-tumor therapy will be cause for early discontinuation of study 
treatment.  
Use of concurrent investigational agents is not permitted.
5.8 Duration of Therapy
In the absence of treatment delays due to adverse events, patients will 
receive 6 weeks of treatment unless one of the following criteria applies:
•
Disease progression
•
Intercurrent illness that prevents further administration of treatment
•
Unacceptable adverse events
•
Patient becomes pregnant
•
Patient decides to withdraw from the study or
•
General or specific changes in the patient’s condition that render the
patient unacceptable for further treatment in the judgment of the 
investigator.
5.9 Duration of Follow up

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Patients will be followed for 24 months after completion of radiation. Patients 
removed from study for unacceptable adverse events that are related to the 
study treatment will be followed until resolution or stabilization of the adverse 
event.
5.10 Criteria for Discontinuation
Patients will be removed from study when any of the criteria listed in Section 
5.8 applies.  The reason for study removal and the date the patient was 
removed must be documented in the medical record and case report form.
6.0 Risks to Participants
Limited field radiation may not be as successful as whole larynx RT and there 
may be an increased risk of treatment failure
It is unknown if unilateral radiation introduces asymmetric function in the larynx.  
However, single vocal cord targeted therapy (surgery) causes no noticeable 
asymmetric symptoms3 (reduced comfort and exacerbated throat clearing), so the 
risk is anticipated to be small
7.0 Potential Benefits to Participants
Patients will have more dedicated follow-up with laryngology – this potentially 
will lead to better post-treatment function.
Patients will receive therapy to a smaller volume, and potentially have improved 
functional outcomes as a consequence.
 
8.0 Cost to Participants
There are no unanticipated costs to participants in this trial.  IMRT is a covered service 
by insurance/Medicare in the treatment of larynx cancer. Stroboscopy is a covered 
service for the follow-up of patients with larynx cancer.  

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9.0 Study Calendar
Screening
Pre-TX
WK
1 RT
WK  
2 RT
WK
3 RT
WK
4 RT
WK
5 RT
WK
6 RT
1 
Month
3 
Month
6 
Month
9 
Month
12 
Month
16
Month
20 
Month
24 
Month
Medical HistoryC
X
Physical ExamC
X
Vital SignsB,C
X
X
X
X
X
X
X
X
X
Performance 
StatusC
X
X
X
X
X
X
X
X
X
Pregnancy TestA
XA
CT NeckC
X
CT Simulation
X
Informed ConsentC
X
Video Stroboscopy 
and Functional 
AssessmentD
X
X
X
X
X
X
X
Patient 
Questionnaire –
EAT-10
X
X
X
X
X
X
X
Adverse Event 
Evaluation
X
X
X
X
X
X
X
X
X
IMRT
X
X
X
X
X
X
TREATMENT COMPLETE
A) A Serum pregnancy test must be performed on WOCBP within 14 days prior to exposure to radiation. The first study-related exposure is at the time of the CT scan of the 
neck.
B) Vital signs include temperature, blood pressure, pulse, respiration rate
C) All screening procedures must be obtained within 30 days of registration.
D) During the assessment the following forms will be completed:
-Voice Handicap Index (VHI)
-Grade, roughness, breathiness, asthenia, and strain (GRBAS) scale
-Penetration aspiration scale (PAS)

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10.0 Adverse Events 
10.1 Definitions
10.1.1 Adverse Events (AE) is any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom or disease temporally 
associated with the use of a medicinal (investigational) product, treatment or 
procedure regardless of whether it is considered related to the medical 
treatment or procedure (NCI CTEP Guidelines March 28, 2011)
10.1.2 Serious Adverse Event (SAE) is an AE that is fatal or life 
threatening, requires inpatient hospitalization or prolongation of existing 
hospitalization (for > 24 hours), persistent or significant incapacity or 
substantial disruption of the ability to conduct normal life functions, or is a 
congenital anomaly/ birth defect, or results in any important medical event 
that may not result in death, be life threatening, or require hospitalization 
may be considered an SAE when, based upon appropriate medical 
judgment, may jeopardize the subject and may require medical or surgical 
intervention to prevent any of the above outcomes.  A “life-threatening” 
adverse event places the patient at immediate risk of death in the judgment 
of the investigator or sponsor.
10.1.3 Severity Rating
 
The investigator will evaluate the severity of each adverse event.  NCI 
Common Terminology Criteria for Adverse Events (CTCAE v.4.0) or study 
specific toxicity tables provided in the protocol define severity.  If not 
included in CTCAE v.4.0, severity is expressed in numerical grade using the 
following definitions:
1.
Grade 1: Mild-asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated.
2.
Grade 2: Moderate-minimal, local or noninvasive intervention 
indicated; limiting age appropriate instrumental ADL.
3.
Grade 3: Severe-severe or medically significant but not immediately 
life-threatening; hospitalization or prolongation of hospitalization 
indicated; disabling; limiting self care ADL.
4.
Grade 4: Life-threatening consequences; urgent intervention indicated. 
5.
Grade 5: Death related to AE
10.1.4 Attribution/Relationship to study drug 
1. Definite – clearly related
2. Probable – likely related
3. Possible – may be related
4. Unlikely – doubtfully related
5. Unrelated – clearly not related

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10.1.5 Expectedness
 
An Expected Adverse Event is one where the specificity or severity is 
consistent with the current information available from the resources.
An Unexpected Adverse Event is one where the nature, severity, or 
frequency of the event is related to participation in the research is not 
consistent with either:
1. The known or foreseeable risk of adverse events associated with the 
procedures involved in the research that are described in (a) the 
protocol-related documents, such as the IRB-approved research 
protocol, any applicable investigator brochure, and the current IRB-
approved informed consent document, and (b) other relevant sources 
of information, such as product labeling and package inserts: or
2. The expected natural progression of any underlying disease, disorder, 
or condition of the subject (s) experiencing the adverse event and the 
subjects(s) predisposing risk factor profile for the adverse event.
(OHRP Guidance on reviewing unanticipated problems 2007)
10.2 Recording and Reporting Responsibilities
10.2.1 Investigative site recording responsibilities:
1. Upon identification of an AE or SAE, the site investigator will 
utilize the above definitions to properly classify the event.  Each 
category listed above must be recorded for each event.
2. All AEs and SAEs will be recorded in the “AE case report forms” 
(CRF) and in progress reports with details about the grade and 
attribution of each episode, action taken with respect to the study 
drug, and the patient’s outcome will be recorded in the CRF.  All 
events will be recorded on case report forms for the duration of the 
study until they resolve.
3. All SAEs will be recorded on the FDA MedWatch form 3500a.  
After submitting the initial report it may be necessary to submit 
follow up reports to the ISRU, Sponsor and the FDA should the 
event require further investigation.
10.2.2 Investigative site reporting responsibilities:
1. The investigator/ site is responsible to report all SAEs to the ISRU 
within 24 hours of becoming aware of the event.  A written report 
must follow within 48 hours.

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2. Each investigator is responsible to report all AEs/SAEs to their local 
IRB following guidelines set by that IRB.  The FCCC OCR reserves 
the right to request an event be reported to the IRB at their 
discretion.  Copies of events reviewed by the IRB must be emailed to 
SAE.FCCC@fccc.edu.
3. If the investigator or IRB feels the event warrants a revision to the 
informed consent that was not already initiated by the ISRU, draft 
revisions will be made in track changes and submitted to the ISRU 
for consideration.  Any consent revisions must receive ISRU 
approval prior to submission to the IRB.
4. Any investigator who is in doubt of whether a particular AE needs to 
be reported is directed to call the FCCC ISRU for confirmation with 
the Principal Investigator
5. If the results of an investigator or OCR investigation show an 
adverse event not initially determined to be reportable is so 
reportable, the investigator will report the event following the above 
guidelines based on the date the determination is made.
6. Copies of all related correspondence and reporting documents must 
be submitted to the ISRU and will be maintained in a regulatory file.
The participating site should report events to:
Investigator-Sponsored Research Unit
Office of Clinical Research
 
           Fox Chase Cancer Center
SAE.FCCC@fccc.edu
10.2.3 OCR Reporting Responsibilities:
1. Adverse events which meet all of the following criteria must be 
reported to all participating institutions for IRB submission within 2 
weeks of notification of the event.  
i.
Unexpected (in terms of nature, severity, or frequency) given (a) 
the research procedures that are described in the protocol-related 
documents, such as the IRB-approved research protocol and 
informed consent document; and (b) the characteristics of the 
subject population being studied;
ii. Possibly related to participation in the research (possibly related 
means there is a reasonable possibility that the incident, 
experience, or outcome may have been caused by the procedures 
involved in the research); and

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iii. Serious (refer to above definition) or otherwise one that suggests 
that the research places subjects or others at a greater risk of 
physical or psychological harm than was previously known or 
recognized.
2. If the adverse event requires modification of the study protocol and 
informed consent, these changes will be provided to all participating 
institutions in the form of an amendment from the OCR for each site’s 
IRB of record along with the report of the adverse event.  
3. Copies of all related correspondence and reporting documents will be 
maintained in a centralized regulatory file for this study at ISRU.
10.3 Pregnancy 
All WOCBP should be instructed to contact the Investigator immediately if 
they suspect they might be pregnant (e.g., missed or late menstrual period) at 
any time during study participation.
In the event of a confirmed pregnancy in a patient participating in the study, 
the Investigator must immediately notify the Fox Chase Cancer Center 
Investigator-Sponsored Research Unit. 
11.0 Statistical Analysis
This is a single arm phase II trial. Prior head and neck investigations of IMRT to 
minimize 3D conformal toxicity have anticipated (and demonstrated) a 30% decrease in 
symptoms when IMRT is utilized38.  Non-randomized analyses have suggested that the 
benefit of IMRT approaches a 50% decrease in symptoms39.  Thus, to be conservative, 
the null hypothesis of this analysis is that two year VHI scores will be 33% lower than 
baseline. This represents a decline from an average VHI global score of 44 to about 29, 
a decline of 15 points. Our alternative of interest is a 50% decline in VHI global score, 
a decline of 22 points.  L. Di Nicola et al (ref) tabulated such scores and we have taken 
their estimate of the standard deviation at baseline of VHI global score, std = 8.5. We 
used this same value for the 2 year score, which is not given by Di Nicola, but is close 
to the 3 year score when VHI scores have further declined.  This, in turn, gives the std 
of baseline less 2 year scores of 8.5 times 1.414. VHI average scores are estimated to be 
normally distributed.
We will obtain baseline and 2 year VHI scores for an initial cohort of 15 patients.  We 
will terminate the study after the first 15 patients have been evaluated at 2 years if their 
average decline is less than 15. Otherwise we will recruit an additional 15 patients. If 
the overall average of all 30 patients is at least 19.2 we will reject the null hypothesis. 
The design has 50% chance of early stopping under the null and a 2.58% chance of 
early stopping in error. The overall type I error is 5% and the study power is 85%.
We will test the null hypothesis that at most 85% of patients will achieve local control 
versus the alternative that at most 95% of them will. If less than 13 of the initial cohort 

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of 15 experience local control, we will interrupt the study for futility. If at least 28 of 30 
acquire local control we will reject the null and declare the local control rate to be 95%. 
The chance of early stopping for lack of local control is 40% when the true local 
control rate is 85%. The chance of early stopping in error is 3.6%. The overall power is 
81% and overall type I error is 15.1%.
12.0 Data and Safety Monitoring Plan
This is a deintensification study – patients will be receiving a smaller field of 
radiation to the same dose as standard therapy.  
Therefore, this study is felt to represent a minimal risk to patient safety outside of the 
primary endpoint.
Even though the investigational treatment is the same dose as prescribed in the 
standard of care but to a smaller volume, unknown factors relating to toxicity will not 
be discounted.  We accept the possibility of at most 5% SAEs among our patients and 
will consider the treatment too toxic if a 20% SAE rate is encountered.  
If 3 patients have a SAE within the first cohort of 15 treatments, the trial will be 
terminated.  
If 5 patients among the 30 experience a DLT the treatment will be considered too 
toxic and will not be pursued further.  The chance of early termination if the SAE rate 
is 5% is 3.62% and the rate of early termination when the true SAE rate is 20% is 
60.2%.  
The overall chance of declaring the treatment too toxic in error is 4.34% and this 
chance when the true toxic rate is 20% is 79.3%.
Per standard institutional protocol, patients will have acute toxicity monitored at least 
weekly using CTCAE v4.0.
12.1 Monitoring Plan 
FCCC ISRU will monitor the medical and study records of each participant 
accrued throughout the course of the study.  In addition, the ISRU will collect 
and report data to the study Principal Investigator who will review these data 
on a regular basis at a rate dependent on subject accrual.  All serious adverse 
events (SAEs) will be reviewed on a real time basis first by the study site PI 
and subsequently by the ISRU and study PI as applicable.
12.2 Data Safety Monitoring Board  
Interim analysis of toxicity, outcome and ongoing scientific investigations 
may be performed at least every 6 months by the Fox Chase Cancer Center 

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Data Safety Monitoring Board (FCCC DSMB).  In this capacity the FCCC 
DSMB will serve as an advisory committee to the OCR.  The FCCC DSMB 
will review those aspects of this trial that are outlined in the responsibilities 
section of the Data and Safety Monitoring Plan (DSMP).  If the committee 
decides that changes should be made to this trial, it will make 
recommendations in writing to the Study Principal Investigator, the Associate 
Director of Clinical Research, and the Protocol Management Executive 
Committee, which, in turn, have the authority to approve or disapprove these 
recommendations.  These changes will be discussed with the Study Principal 
Investigator before they are implemented.  These changes may include early 
termination of accrual.  Other changes might include altering the accrual goals 
or changing the eligibility criteria for the trial.
13.0 Administrative  
This study will be conducted in accordance will local, state and Federal regulations 
and according to accepted good clinical practice guidelines.
13.1 Data Reporting
The FCCC Study Monitor will request case report forms to be completed 
within 2 weeks of the protocol visit.  Participating sites are responsible to 
respond to queries prior to the next scheduled monitoring visit.  
The ISRU is responsible for compiling and submitting data to the study PI and 
statistician on an ongoing basis for monitoring as described in the data safety 
monitoring plan and reporting to the Extramural Data and Safety Monitoring 
Board.
All patient information will be stored in an EDC system accessible only to the 
study team members for the purpose of entering, reviewing and analyzing 
data.  Any paper records, such as case report files, produced will be stored in  
in a secure location. 
The ISRU is responsible for distributing and tracking review of all Safety 
Reports and study specific Serious Adverse Events
13.2 Retention of Records  
The FCCC ISRU must be notified of any plans to move records to an offsite 
location prior to doing so.
13.3 Informed Consent
The IRB approved informed consent documents must be signed by the patient, 
or the patient’s legally authorized representative, before his or her 

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participation in the study.  The case history for each patient shall document 
that informed consent was obtained prior to participation in the study.  A copy 
of the informed consent documents must be provided to the patient or the 
patient’s legally authorized representative.  
If applicable, they will be 
provided in a certified translation of the local language.
Original signed consent forms must be filed in each patient’s study file or 
medical record with a copy in the study file.

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14.0 References
1.
Ridge JA, Lawson J, Yom SS, et al: American College of Radiology 
Appropriateness Criteria((R)) treatment of stage I T1 glottic cancer. Head Neck 36:3-8, 2014
2.
Al-Mamgani A, van Rooij PH, Woutersen DP, et al: Radiotherapy for T1-2N0 
glottic cancer: a multivariate analysis of predictive factors for the long-term outcome in 1050 
patients and a prospective assessment of quality of life and voice handicap index in a subset of 
233 patients. Clin Otolaryngol 38:306-12, 2013
3.
van Gogh CD, Verdonck-de Leeuw IM, Wedler-Peeters J, et al: Prospective 
evaluation of voice outcome during the first two years in male patients treated by radiotherapy or 
laser surgery for T1a glottic carcinoma. Eur Arch Otorhinolaryngol 269:1647-52, 2012
4.
Million RR CN, Mancuso AAL: Larynx, in Million RR, Cassisi NJ (eds): 
Management of Head and Neck Cancer: A Multidisciplinary Approach (ed 2).431-497, 1994
5.
Chera BS, Amdur RJ, Morris CG, et al: T1N0 to T2N0 squamous cell carcinoma 
of the glottic larynx treated with definitive radiotherapy. Int J Radiat Oncol Biol Phys 78:461-6, 
2010
6.
Yamazaki H, Nishiyama K, Tanaka E, et al: 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 64:77-82, 2006
7.
Trotti A, 3rd, Zhang Q, Bentzen SM, et al: Randomized Trial of 
Hyperfractionation Versus Conventional Fractionation in T2 Squamous Cell Carcinoma of the 
Vocal Cord (RTOG 9512). Int J Radiat Oncol Biol Phys 89:958-63, 2014
8.
Canis M, Ihler F, Martin A, et al: Transoral laser microsurgery for T1a glottic 
cancer: Review of 404 cases. Head Neck, 2014
9.
van de Water TA, Bijl HP, Westerlaan HE, et al: Delineation guidelines for 
organs at risk involved in radiation-induced salivary dysfunction and xerostomia. Radiother 
Oncol 93:545-52, 2009
10.
Warde P, O'Sullivan B, Bristow RG, et al: T1/T2 glottic cancer managed by 
external beam radiotherapy: the influence of pretreatment hemoglobin on local control. Int J 
Radiat Oncol Biol Phys 41:347-53, 1998
11.
Chatani M, Matayoski Y, Masaki N, et al: Radiation therapy for early glottic 
carcinoma (T1N0M0). The final results of prospective randomized study concerning radiation 
field. Strahlenther Onkol 172:169-72, 1996
12.
Trotti A, Pajak TF, Gwede CK, et al: TAME: development of a new method for 
summarising adverse events of cancer treatment by the Radiation Therapy Oncology Group. 
Lancet Oncol 8:613-24, 2007
13.
Brandstorp-Boesen J, Falk RS, Boysen M, et al: Long-term trends in gender, T-
stage, subsite and treatment for laryngeal cancer at a single center. Eur Arch Otorhinolaryngol, 
2014
14.
So NM, Lam WW, Chook P, et al: Carotid intima-media thickness in patients 
with head and neck irradiation for the treatment of nasopharyngeal carcinoma. Clin Radiol 
57:600-3, 2002
15.
Dorresteijn LD, Kappelle AC, Boogerd W, et al: Increased risk of ischemic 
stroke after radiotherapy on the neck in patients younger than 60 years. J Clin Oncol 20:282-8, 
2002
16.
Smith GL, Smith BD, Buchholz TA, et al: Cerebrovascular disease risk in older 
head and neck cancer patients after radiotherapy. J Clin Oncol 26:5119-25, 2008
17.
Rosenthal DI, Fuller CD, Barker JL, Jr., et al: Simple carotid-sparing intensity-
modulated radiotherapy technique and preliminary experience for T1-2 glottic cancer. Int J Radiat 
Oncol Biol Phys 77:455-61, 2010

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18.
Chera BS, Amdur RJ, Morris CG, et al: Carotid-sparing intensity-modulated 
radiotherapy for early-stage squamous cell carcinoma of the true vocal cord. Int J Radiat Oncol 
Biol Phys 77:1380-5, 2010
19.
Rancati T, Schwarz M, Allen AM, et al: Radiation dose-volume effects in the 
larynx and pharynx. Int J Radiat Oncol Biol Phys 76:S64-9, 2010
20.
Di Nicola L, Gravina GL, Marampon F, et al: The impact of conventional or 
hypofractionated radiotherapy on voice quality and oncological outcome in patients with early 
glottic cancer. Oncol Rep 24:1383-8, 2010
21.
Lau VH, Leonard RJ, Goodrich S, et al: Voice quality after organ-preservation 
therapy with definitive radiotherapy for laryngeal cancer. Head Neck 34:943-8, 2012
22.
van Loon Y, Sjogren EV, Langeveld TP, et al: Functional outcomes after 
radiotherapy or laser surgery in early glottic carcinoma: a systematic review. Head Neck 34:1179-
89, 2012
23.
Peretti G, Piazza C, Del Bon F, et al: Function preservation using transoral laser 
surgery for T2-T3 glottic cancer: oncologic, vocal, and swallowing outcomes. Eur Arch 
Otorhinolaryngol 270:2275-81, 2013
24.
Yoo J, Lacchetti C, Hammond JA, et al: Role of endolaryngeal surgery (with or 
without laser) versus radiotherapy in the management of early (T1) glottic cancer: A systematic 
review. Head Neck, 2013
25.
Remmelts AJ, Hoebers FJ, Klop WM, et al: Evaluation of lasersurgery and 
radiotherapy as treatment modalities in early stage laryngeal carcinoma: tumour outcome and 
quality of voice. Eur Arch Otorhinolaryngol 270:2079-87, 2013
26.
Abdurehim Y, Hua Z, Yasin Y, et al: Transoral laser surgery versus radiotherapy: 
systematic review and meta-analysis for treatment options of T1a glottic cancer. Head Neck 
34:23-33, 2012
27.
Hirano M: Psycho-acoustic evaluation of voice. Disorders of Human 
Communication, 5, Clinical Examination of Voice In: Arnold, Winckel, Wyke, eds. , 1981
28.
Jacobson BH JA, Grywalsky C, et al.: The voice handicap index (VHI): 
development and validation. American Journal of Speech Language Pathology 6:66-70, 1997
29.
Bajaj Y, Uppal S, Sharma RK, et al: Evaluation of voice and quality of life after 
transoral endoscopic laser resection of early glottic carcinoma. J Laryngol Otol 125:706-13, 2011
30.
Rosenbek JC, Robbins JA, Roecker EB, et al: A penetration-aspiration scale. 
Dysphagia 11:93-8, 1996
31.
Salassa JR: A functional outcome swallowing scale for staging oropharyngeal 
dysphagia. Dig Dis 17:230-4, 1999
32.
Belafsky PC, Mouadeb DA, Rees CJ, et al: Validity and reliability of the Eating 
Assessment Tool (EAT-10). Ann Otol Rhinol Laryngol 117:919-24, 2008
33.
Mendenhall WM, Werning JW, Hinerman RW, et al: Management of T1-T2 
glottic carcinomas. Cancer 100:1786-92, 2004

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Appendix I
FCCC Health Voice, Airway, and Swallowing Center
Eating Assessment Tool – 10 (EAT-10)
Circle the appropriate response:
To what extent are the following scenarios 
problematic for you?
0 = No problem   
4  = Severe problem
1.    My swallowing problem has caused me to lose weight.
0
1
2
3
4
2.
My swallowing problem interferes with my ability to go 
out for meals.
0
1
2
3
4
3.
Swallowing liquids takes extra effort.
0
1
2
3
4
4.
Swallowing solids takes extra effort.
0
1
2
3
4
5.
Swallowing pills takes extra effort.
0
1
2
3
4
6.
Swallowing is painful.
0
1
2
3
4
7.
The pleasure of eating is affected by my swallowing.
0
1
2
3
4
8.
When I swallow food sticks in my throat.
0
1
2
3
4
9.
I cough when I eat.
0
1
2
3
4
10. Swallowing is stressful.
0
1
2
3
4
TOTAL
Participant Signature:________________________________________
Date:_________________________