Phase IV Trial to Use Stereotactic Body Radiotherapy for Head and Neck Tumors
Phase: PHASE4
Conditions: Squamous Cell Carcinoma of the Head and Neck, Nasopharyngeal Carcinoma, Salivary Gland Cancer, Head and Neck Sarcoma, Paraganglioma of Head and Neck, Chordoma of Head and Neck, Chondrosarcoma of Head and Neck, Angiofibroma of Head and Neck
Sponsor: Mercy Research

 
 
 
 
 
 
PHASE IV TRIAL TO USE STEREOTACTIC BODY 
RADIOTHERAPY (SBRT) FOR HEAD AND NECK TUMORS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigators 
 
 
 
Radiation Oncology 
Robert Frazier, M.D. 
 
 
Kathy Baglan, M.D. 
 
 
Jeffrey Craft, M.D. 
 
 
Julie Mai, M.D. 
 
 
Jaymeson Stroud, M.D. 
 
 
David C. Pratt Cancer Center 
 
 
(314) 251-6844 
 
 
Fax (314) 251-4337 
 
 
Oncology Research 
Bethany Sleckman, M.D. 
 
 
David C. Pratt Cancer Center 
 
 
(314) 251-7057 
 
 
Fax (314) 251-5665 
 
 
Activation Date: 
August 1, 2008 
 
Amendment 1: 
February 26, 2009 
 
Amendment 2:  
February 4, 2013 

Amendment 2: February 4, 2013 
1
Index 
 
1   Introduction/Background ……………………………………………………………………………3 
2 
Objectives 
 
2.1 
Hypothesis ………………………….……………………………………………………….4 
 
2.2 
Study Design ……………………………………………….………………………………..4 
 
2.3 
Endpoints ………………………….…………………………………………………………4 
3 
Patient Selection  
 
3.1 
Eligibility Criteria …………………………………………………………………………...4 
 
3.2 
Exclusion Criteria …………………………………………………………………………...4 
4 
Pretreatment Evaluation …………………………………………………………………………….5 
5 
Simulation …………………………………………………………………………………………..5 
6 
Radiation Treatment Planning 
 
6.1 
Target Definition …………………………………………………………………………….5 
 
6.2 
Dose Specification …………………………………….……………………………………..5 
 
6.3 
Normal Tissue Dose Constraints …………………………………………………………….6 
7 
Stereotactic Body Radiotherapy Treatment Delivery 
 
7.1 
Premedication ……………………………………………………………………………..…7 
 
7.2 
Treatment …………………………………………………………………………………….7 
8 
Drug Therapy ………………………………………………………………………………………..8 
9 
Patient Assessment 
 
9.1 
Study Parameters …………………………………………………………………………….8 
 
9.2 
Response Evaluation ……………………………………………………………………….. .8 
 
9.3 
Toxicity ……………………………………………………………………………………....8 
 
9.4 
Patient Withdrawal …………………………………………………………………………..9 
10 Risk/Benefit Analysis 
 
 
10.1 Risk associated with SBRT for Head and Neck Tumors …………………………….….…. .9 
 
10.2 Minimization of Risks ……………………………………………………………………….10 
 
10.3 Potential Patient Benefits …………………………………………………………………... .10 
 
10.4 Justification of the Study …………………………………………………………………….10 
 
10.5 Statistical Analysis …………………………………………………………………………..10 
11 References …………………………………………………………………………………………...11 
12 Appendices 
 
12.1 Appendix I - Sample Informed Consent ……………………………..….…………………...12 
 
12.2 Appendix II - Performance Status …………………………………..….…………………....17 
 
12.3 Appendix III - Toxicity Score ……………………………….…...………………………….18 
 
12.4 Appendix IV - Patient Demographic Form ……………………..…..…….…………….…...22 
 
12.5 Appendix V – Treatment Form ……………………………………………………………....24 
 
12.6 Appendix VI - Patient Follow-up Form ……….….…………..……………………………..25 
 
 
 
 
 
 
 
 
 
 
 
 

Amendment 2: February 4, 2013 
2
PHASE IV TRIAL TO USE STEREOTACTIC BODY 
RADIOSURGERY (SBRT) FOR BENIGN AND MALIGNANT 
HEAD AND NECK TUMORS 
 
 
SCHEMA 
 
 
 
 
 
R 
Stereotactic Body Radiotherapy (SBRT) 
 
 
E 
Benign Head and Neck Tumors: Paraganglioma  
 
 
 
 
Chordoma  
 
G 
 
 
Chondrosarcoma 
 
 
I 
Suggested Dose-Fractionation: 14-16 Gy / 1 fraction 
 
 
 
 
18-21 Gy / 3 fractions (6-7 Gy per fraction) 
 
S 
 
 
25-45 Gy / 5 fractions (5-9 Gy per fraction) 
 
 
T 
Malignant Head and Neck Tumors: Nasopharynx Cancer 
 
 
 
 
 
Unresectable Cancers 
 
E 
 
 
 
Suggested Dose-Fractionation: 8-12 Gy / 1 fraction 
 
R 
 
 
12-18 Gy / 3 fractions (4-6 Gy per fraction) 
 
 
 
 
35-45 Gy / 5 fractions (7-9 Gy per fraction) 
 
 
 
 
Chemotherapy 
Chemotherapy may be given at the discretion of the patient’s medical oncologist.  However, ideally 
chemotherapy, including immune-modifying drugs, should not have been given within 2 weeks of starting 
radiation and should not resume until at least 2 weeks after completing radiation.  
 
Eligibility 
- Patient age > 18 years 
- Zubrod performance status of 0-3 
- Benign head and neck tumors such as paragangioma (ex. Glomus jugulare, glomus tympanicum, carotid  
 body tumors),chordoma, chondrosarcoma, angiofibroma 
- Malignant head and neck cancers such as invasive squamous cell carcinoma, adenocarcinoma,  
 nasopharyngeal carcinoma, salivary gland cancers, and sarcomas 
- No pregnant or lactating women (negative pregnancy test for women of child-bearing age) 
- Signed study-specific consent form 

Amendment 2: February 4, 2013 
3
1.0   Introduction 
 
 
Stereotactic Body Radiotherapy (SBRT) is a novel technique in the radiation oncology community.  
SBRT has evolved as a treatment option for malignant skull base lesions, and can be used to treat 
recurrent head and neck cancers (1-6).   
 
 
Nasopharynx cancer has been treated effectively with radiation therapy.  Due to recent advances in 
radiation oncology and the combined use of chemotherapy, improvements in local control and overall 
survival have been obtained over the last decade.  Local recurrence still occurs and generally the outcome 
for salvage treatment has been poor.  Due to the anatomical location of the nasopharynx, recurrent 
nasopharynx cancer is difficult to treat.  SBRT has been use successfully to treat recurrent disease (3-6).  
In addition to recurrent disease, SBRT has been used successfully as a boost after external beam radiation 
to safely increase the radiation dose to tumors (7,8).  
 
For patients with locally recurrent head and neck cancer arising form the oral cavity, oropharyx, 
larynx, or hypopharynx treatment options may be limited.  For patients who have received prior radiation 
therapy, additional standard external beam radiation therapy may not be an option.  For patients who 
develop recurrence at the skull base, complete surgical resection usually can not be achieved.  Patients 
may experience symptoms which can diminish their quality of life.  Pain is a common symptom of 
recurrent head and neck cancer.  Stereotactic body radiotherapy may provide excellent palliation for 
patients with recurrent head and neck cancers.  Most patients who receive SBRT have excellent palliation 
of pain.  In addition, some patients may achieve long term local control (9-11).   
 
Chordomas are locally aggressive and destructive tumors with high recurrence rates.  
Chondrosarcomas arise from the skull base and tend to affect lower cranial nerves.  Complete surgical 
resection is rarely feasible for these lesions.  Various modalities of fractionated radiation therapy have 
been used to increase local control.  Stereotactic body radiotherapy delivers more conformal radiation 
with greater radiobiological effect than conventional radiation therapy.  Compared to conventional 
radiation therapy, SBRT may reduce toxicity to normal surrounding structures and potentially cause fewer 
complications.  Martin et al. from the University of Pittsburg reported on 28 patients treated with SBRT 
as a boost after external beam radiation or as the sole treatment.  The median follow up was 7 years.  The 
five year local control rate for chondrosarcomas was 80%. The five year local control rate for chordomas 
was 62%.  One patient developed mild dizziness and nausea which was controlled with a two week course 
of corticosteroids.  No long term side effects were reported.  The authors concluded that SBRT is an 
important treatment option for chordomas and chondrosarcomas(12-15).   
 
 
    

Amendment 2: February 4, 2013 
4
2.0 Objectives 
 
 
This study will evaluate the local control rates as well as acute and late toxicity rates of stereotactic 
body radiotherapy (SBRT) for the treatment of benign and malignant head and neck tumors. 
 
 
2.1 Hypothesis 
 
 
2.1.1 For selected patients with primary or recurrent head and neck tumors, stereotactic body 
radiotherapy (SBRT) is technically feasible with acceptable complication rates. 
 
 
2.2 Study Design 
 
 
2.2.1 Single site, non-randomized, prospective, phase IV sudy 
 
 
2.2.2 Composed of 3 patient groups: 
 
 
 
- Benign tumors, such as paraganglioma (ex. Glomus jugulare, glomus tympanicum,  
                              carotid body tumor) chordoma, chondrosarcoma, as the sole treatment or to gross  
 
 
 
  residual disease after maximal safe resection 
 
 
 
- Malignant tumors, such as nasopharynx cancer and squamous cell carcinoma, after  
 
 
 
  initial external beam radiation (Residual Disease Group) 
 
 
 
- Unresectable malignant tumors, such as nasopharynx cancer and squamous cell  
 
 
 
  carcinoma, adenocarcinoms, and sarcomas which are recurrent after prior radiation  
 
 
 
  (Primary RT Group)   
 
 
2.2.3 Data collected will include baseline patient demographics, pathology data, radiation 
therapy procedure, tumor recurrence data, and toxicities.   
 
 
2.2.4 Follow up data will be collected during the patient’s standard office visits.  The 
 
  
 
anticipated duration of this study is 5 years. 
 
 
2.3 End Points 
 
 
2.3.1 Primary endpoints will be local control rate and complication rate   
 
 
 
- Local recurrence is defined as cancer recurrence within the target volume.  
 
 
 
-  Local control rate will be evaluated by imaging techniques, physical exam and biopsy,  
 
 
 
 if applicable.  
 
 
 
- Evaluation of complication rates (see Section 9.3 for definitions) 
2.3.2 Secondary endpoint will be overall survival 
 
3.0 Patient Selection 
 
 
3.1 Eligibility Criteria 
  
3.1.1 Patient age > 18 years 
  
3.1.2 Zubrod performance status of 0-3 
  
3.1.3 Benign head and neck tumors such as paragangliomas (ex. Glomus jugulare, glomus  
                            tympanicum carotid body tumor), chordoma, chondrosarcoma 
                3.1.4    Malignant head and neck cancers such as invasive squamous cell carcinoma,  
                            adenocarcinoma, nasopharyngeal carcinoma, salivary gland cancers, and sarcoma 
  
3.1.5 No pregnant or lactating women (negative pregnancy test for women of child-bearing  
  
  
age) 
  
3.1.6 Signed study-specific consent form 
 
 
3.2 Exclusion Criteria 
 
 
3.2.2 
Pregnant or lactating women, due to potential exposure of the fetus to RT and  
 
 
 
unknown effects of RT on lactating females  
 
 
3.2.3 
Patients with psychiatric or addictive disorder that would preclude obtaining informed  
 
 
 
consent 

Amendment 2: February 4, 2013 
5
 
4.0 Pretreatment Evaluation 
 
 
4.1 Patient history, including prior radiation and chemotherapy treatments 
 
4.2 Physical examination with the location and palpable size of the lesion in cm 
 
4.3 CT scan of involved head and neck region 
 
4.4 Other imaging studies are optional, including PET 
 
5.0 Simulation 
 
 
5.1 
Fabrication of a custom mask and bite block immobilization device or placement of a  
 
 
stereotactic head frame 
 
5.2 
Treatment planning CT scan acquired in treatment position with patient’s head immobilized 
 
6.0 Radiation Therapy 
 
 
6.1 
Target Definition 
 
 
6.1.1 
Gross tumor volume (GTV) is contoured on the planning CT scan.  If available, 
Diagnostic CT scan, MRI and/or PET images may be utilized to construct the GTV by 
registering them to the planning CT dataset. 
 
 
6.1.2 
At the discretion of the treating radiation oncologist, the GTV margins may be  
 
 
 
expanded to form the planning target volume (PTV). 
 
 
 
6.2 
Dose-Specification 
 
 
6.2.1 
Radiation beams will conform to the PTV outline without additional margin and the  
 
 
 
dose will be prescribed to the isodose line (IDL) that covers at least 95% of the PTV,  
 
 
 
which is typically around 80%. 
 
 
6.2.2 
SBRT dose-fractionation scheme will be chosen at the discretion of the treating  
 
 
 
radiation oncologist, but the normal tissue dose constraints should be maintained. 
 
 
 
Suggested dose-fractionation schemes, derived from the available literature, are listed 
 
 
 
below.  Also included are the corresponding biologic equivalent dose (BED) for each 
 
 
 
based on the linear-quadratic model:  
 
 
 
 
 
SBRT scheme 
BED1 
(α/β=10) 
BED2 
(α/β=3) 
Equivalent 
2 Gy/Fx 
Dose1 
(α/β=10) 
Equivalent 
2 Gy/Fx 
Dose2 
(α/β=3) 
 
Paraganglioma 
 
 
14 Gy x 1 
15 Gy x 1 
16 Gy x 1 
 
6 Gy x 3 
7 Gy x 3 
 
5 Gy x 5 
 
33.6 Gy 
37.5 Gy 
41.6 Gy 
 
28.8 Gy 
35.7 Gy 
 
37.5 
79.3 
90 
101 
 
54 
70 
 
66.7 
28 
31.3 
34.7 
 
24 
29.9 
 
31.3 
47.6 
53.9 
60.5 
 
32.4 
41.9 
 
40.0 

Amendment 2: February 4, 2013 
6
Chordoma 
Chondrosarcoma 
 
6 Gy x 5 
7 Gy x 5 
8 Gy x 5 
9 Gy x 5 
 
48 
59.5 
72 
85.5 
90 
117 
147 
180 
40 
49.6 
60 
71.3 
53.9 
70 
88 
108 
Malignant Cancer 
(Residual Disease) 
 
8 Gy x 1 
9 Gy x 1 
10 Gy x 1 
11 Gy x 1 
12 Gy x 1 
 
4 Gy x 3 
5 Gy x 3 
 
14.4 
17.1 
20 
23.1 
26.4 
 
16.8 
22.5 
29.3 
36 
43 
51.3 
60 
 
28 
40 
12 
14.3 
16.7 
19.3 
22 
 
14 
18.8 
17.6 
21.6 
25.8 
30.1 
35.9 
 
16.8 
23.9 
Malignant Cancers 
(Recurrent) 
 
8 Gy x 1 
9 Gy x 1 
10 Gy x 1 
11 Gy x 1 
12 Gy x 1 
13 Gy x 1 
14 Gy x 1 
 
4 Gy x 3 
5 Gy x 3 
6 Gy x 3 
 
7 Gy x 5 
8 Gy x 5 
9 Gy x 5 
 
 
14.4 
17.1 
20 
23.1 
26.4 
29.9 
33.6 
 
16.8 
22.5 
28.8 
 
59.5 
72 
85.5 
 
 
29.3 
36 
43 
51.3 
60 
69.3 
79.3 
 
28 
40 
54 
 
117 
147 
180 
 
 
12 
14.3 
16.7 
19.3 
22 
24.9 
28 
 
14 
18.8 
24 
 
49.6 
60 
71.3 
 
 
17.6 
21.6 
25.8 
30.1 
35.9 
41.6 
47.6 
 
16.8 
23.9 
32.4 
 
70 
88 
108 
 
 
 
 
 
1Cancers are assumed to have an α/β ratio of approximately 10 
 
 
 
 
2Normal tissues are assumed to have an α/β ratio of approximately 3 
 
 
6.3 
Normal Tissue Dose Constraints 
 
 
6.3.1 
Normal tissue dose constraints will depend on whether nearby critical normal tissues  
 
 
 
 
have received prior external beam radiation, what dose they received, and the time  
 
 
 
 
between prior radiation and the current SBRT treatment course.  These dose limits  
 
 
 
 
will ultimately be determined by the treatment radiation oncologist.  For patients who  
 
 
 
 
have received prior radiation therapy, every effort should be taken to limit the  
 
 
 
 
cumulative doses to adjacent critical normal tissues as follows based on standard  
 
 
 
 
fractionation schemes (1.8-2 Gy per day): 
 
 
 
 
Spinal cord – Dmax = 50 Gy 
 
 
 
 
Brainstem – Dmax = 60 Gy 
 
 
 
 
Optic Nerves – Dmax = 50 Gy 
 
 
 
 
Optic Chiasm - Dmax = 54 Gy 
 
 
6.3.2 
For patients in whom SBRT is planned following initial standard- 
 
 
 
 
fractionation wide-field external beam radiation (Residual Disease Group), the initial  
 
 
 
 
radiation course should be designed to limit exposure to adjacent critical normal  
 
 
 
 
tissues as follows: 
 
 
 
 
Spinal cord – Dmax = 40 Gy 

Amendment 2: February 4, 2013 
7
 
 
 
 
Optic Apparatus – Dmax = 50 Gy 
 
 
 
 
Brainstem – Dmax = 50 Gy 
 
 
6.3.3 
For patients who have not received prior radiation therapy, the following dose limits  
 
 
 
 
should be maintained: 
Structure 
1 Fraction 
3 Fractions 5 Fractions 
Optic Chiasm 
8 Gy Dmax 
12 Gy Dmax 
14 Gy Dmax 
Optic Nerve 
8 Gy Dmax 
12 Gy Dmax 
14 Gy Dmax 
Brainstem  
14 Gy Dmax 
22 Gy Dmax 
27 Gy Dmax 
Spinal Cord 
8 Gy to < 0.5 cc 
10 Gy to < 0.3 cc 
12 Gy to < 0.15 cc 
18 Gy Dmax 
22 Gy Dmax 
Brachial Plexus 
14 Gy Dmax 
24 Gy Dmax 
25 Gy Dmax 
Internal Carotid Artery  
in Cavernous Sinus 
25 Gy Dmax 
 
32 Gy Dmax 
 
35 Gy Dmax 
 
Oculomotor Nerves in 
Cavernous Sinus 
30 Gy Dmax 
32 Gy Dmax 
 
35 Gy Dmax 
 
Esophagus 
15 Gy Dmax 
24 Gy Dmax 
30 Gy Dmax 
Skin 
15 Gy Dmax 
24 Gy Dmax 
30 Gy Dmax 
 
 
 
 
 
7.0 Stereotactic Body Radiotherapy Treatment Delivery 
 
 
7.1 
Premedication 
 
 
The decision to premedicate a patient prior to head and neck SBRT is at the discretion of the  
 
 
treating radiation oncologist.  Most patients typically do not need premedication.  The 
 
 
following are a list of agents that have been used by some investigators to potentially reduce  
 
 
patient discomfort and possibly prevent acute and/or late toxicity if used as premedication  
 
 
prior to SBRT.  
 
 
7.1.1 
Corticosteroids (Decadron 4 mg PO or equivalent) 15-60 minutes prior to each  
 
 
 
fraction for the intended purpose of modulating immediate inflammatory effects.   
 
 
7.1.2 
Analgesic premedication to avoid general discomfort during long treatment durations. 
 
 
7.1.3 
Anti-anxity medication for patient comfort during long treatment duration  
 
 
7.2 
Treatment 
 
 
7.2.1 
The medical physics staff will perform routine quality assurance checks on the  
 
 
 
treatment machine to ensure that the mechanical isocenter stability is within  
 
 
 
specification (ie. diameter < 1.5 mm).  
 
 
7.2.2 
The medical physics staff will perform patient-specific quality assurance  
 
 
 
measurements to ensure that the treatment plan is deliverable and that the dose  
 
 
 
distribution is accurate.  
 
 
7.2.3 
The patient will be positioned in the custom immobilization device on the Hexapod®  
 
 
 
treatment couch and aligned with the in-room lasers. 
 
 
7.2.4 
Daily CT localization of the GTV isocenter is required prior to each fraction.  Once  
 
 
 
the patient is properly positioned, a cone-beam CT of the treatment area is acquired,  
 
 
 
fused, and aligned to the treatment planning CT.  Translational and rotational  
 
 
 
adjustments of patient positioning are performed as indicated.  If adjustment are  
 
 
 
required, an orthogonal (ex. AP and LATERAL) set of electronic portal images is then  
 
 
 
obtained prior to treatment to confirm proper alignment of the isocenter. 
 
 
7.2.5 
Either multiple coplanar or noncoplanar static gantry angle intensity-modulated fields 
or rotational arcs will be utilized. 
 
 
7.2.6 
Only photon (x-ray) beams will be used, preferably in energies of 6 MV. 

Amendment 2: February 4, 2013 
8
 
 
 
8.0 Drug Therapy 
 
 
8.1 
The use of chemotherapy is left to the discretion of the medical oncologist. 
 
8.2 
Chemotherapy agents during radiation is not allowed.  If chemotherapy is planned, it should  
 
 
ideally not have been given within 2 weeks of starting radiation and should not resume until at  
 
 
least 2 weeks after completing radiation.  
 
 
9.0 
Patient Assessment 
 
 
9.1 
Study Parameters 
 
 
The following are suggested patient follow-up intervals and evaluations that may be  
 
 
performed to either assess for treatment toxicity or tumor response to SBRT: 
Assessment 
Pre-Rx Post-Rx 
6 wk 
Post-Rx  
3 mo 
Post-Rx 
6 mo 
Post-Rx 
9 mo 
Post-Rx 
1 yr 
History & Physical 
X 
X 
X 
X 
X 
Xb 
Weight 
X 
X 
X 
X 
X 
Xb 
Disease status 
X 
X 
X 
X 
X 
Xb 
Toxicity Assessment 
 
X 
X 
X 
X 
Xb 
Pregnancy test 
Xa 
 
 
 
 
 
CT and/or MRI  
(head and neck) 
X 
X 
- 
X 
- 
Xb 
 
 
 
a 
if clinically appropriate  
 
 
 
b 
clinical examination, late toxicity, and disease status assessment at 3 month intervals for first year,  
 
 
 
 
then at the discretion of the treating radiation oncologist 
 
 
 
 
9.2  
Response Criteria 
 
 
 
9.2.1 
CT scan of the soft tissues of the neck with IV contrast (MRI may be used) 
 
 
 
 
- Local recurrence is defined as tumor recurrence within the planning target volume.  
 
 
 
 
If necessary, a PET/CT scan may be used to aid in diagnoses local tumor  
 
 
 
 
recurrence. 
 
 
 
9.2.2 
PET/CT scan 
 
 
 
 
- May be obtained at the discretion of the treating radiation oncologist if there is  
 
 
 
 
uncertainty on the diagnostic CT scan as to the disease status in the head and neck. 
 
 
 
9.2.3 
A local recurrence is defined as cancer recurrence within the planning target volume.  
 
 
 
9.2.4 
Distant metastases will not be considered a treatment failure unless accompanied  
 
 
 
 
by local recurrence. 
 
 
9.3 
Toxicity 
 
 
9.3.1 
The investigator will report and record all serious adverse events that occur.  Adverse  
 
 
 
events should be reported using the CTC grading system (Appendix III).   
 
 
9.3.2 
Examples of anticipated acute adverse events include: 
 
 
 
 
- General malaise 
 
 
 
 
- Radiation dermatitis – dryness, tanning, redness, itching 
 
 
 
 
- Localized hair loss 
 
 
 
 
- Mucositis 
 
 
 
 
- External otitis 
 
 
 
 
- Otitis Media 
 
 
 
 
- Xerostomia 
 
 
 
 
- Mastoiditis 

Amendment 2: February 4, 2013 
9
 
 
 
 
- Weight loss 
 
 
 
 
- Pharyngitis 
 
 
 
 
- Vertigo 
 
 
 
9.3.3 
Examples of anticipated late adverse events include:   
 
 
 
 
 - Radionecrosis of the temporal bone, skull base, mandible 
 
 
 
 
 - Radionecrosis of brain tissue 
 
 
 
 
 - Soft tissue necrosis 
 
 
 
 
 - CVA 
 
 
 
 
 - Cranial nerve neuropathy 
 
 
 
 
 - Ipsilateral hearing loss 
 
 
 
 
 - Vocal cord paralysis 
 
 
 
 
 - Nasal hemorrhage 
 
 
 
 
 - Localized skin fibrosis, edema, and/or ulceration 
 
 
 
 
 - Radiation-induced malignancy (ex. Fibrosarcoma) 
 
 
9.3.4 
Reporting of unanticipated or serious adverse events will be reported according to the  
 
 
 
institutions IRB policy.  An unanticipated adverse effect is defined as follows: 
 
 
 
 
Any serious adverse effect on health or safety or any life-threatening problem or  
 
 
 
 
death caused by, or associated with, stereotactic body radiotherapy, if that effect,  
 
 
 
 
problem, or death was not previously identified in nature, severity, or degree of  
 
 
 
 
incidence in the investigational plan or application (including a supplementary  
 
 
 
 
plan or application), or any other unanticipated serious problem associated with a  
 
 
 
 
treatment that relates to the rights, safety, or welfare of subjects. 
  
 
9.4 
Patient Withdrawal from Study 
 
 
During the course of the study, it is possible that patients may withdraw or be withdrawn from  
 
 
the study.  Factors that may lead to a withdrawal from the study may include, but are not  
 
 
limited to the following: 
 
 
 
Patient Withdrawal……………At any time a patient may voluntarily withdraw from the  
 
 
 
 
 
 
study.  This withdrawal will not affect their future medical  
 
 
 
 
 
 
treatment or benefits.   
 
 
 
Patient Lost to Follow-Up…….Should a patient be classified as lost to follow-up, efforts  
 
 
 
 
 
 
to contact the patient should be made.  
 
 
 
Physician Decision……………Should a physician decide that continuing in the study is  
 
 
 
 
 
 
detrimental to the health and welfare of the patient, the  
 
 
 
 
 
 
patient may be withdrawn from the study.   
 
 
 
Medical Reason……………….Should the patient condition deteriorate the patient may be  
 
 
 
 
 
 
withdrawn from the study to allow for proper medical care.   
 
 
 
10.0 Risk/Benefit Analysis 
 
 
10.1 Risk associated with Stereotactic Body Radiotherapy for head and neck tumors 
 
 
10.1.1 Acute toxicities reported to occur as a result of SBRT for head and neck tumors  
 
 
 
include, but are not limited to:  
 
 
 
 
 
- General malaise 
 
 
 
 
- Radiation dermatitis – dryness, tanning, redness, itching 
 
 
 
 
- Localized hair loss 
 
 
 
 
- Mucositis 
 
 
 
 
- External otitis 
 
 
 
 
- Otitis Media 
 
 
 
 
- Xerostomia 

Amendment 2: February 4, 2013 
10 
 
 
 
 
- Mastoiditis 
 
 
 
 
- Weight loss 
 
 
 
 
- Pharyngitis 
 
 
 
 
- Vertigo 
 
 
 
 
 
10.1.3 Late toxicities reported to occur as a result of SBRT for head and neck tumors  
 
 
 
include, but are not limited to:  
 
 
 
 
 
 - Radionecrosis of the temporal bone, skull base, mandible 
 
 
 
 
 - Radionecrosis of brain tissue 
 
 
 
 
 - Soft tissue necrosis 
 
 
 
 
 - CVA 
 
 
 
 
 - Cranial nerve neuropathy 
 
 
 
 
 - Ipsilateral hearing loss 
 
 
 
 
 - Vocal cord paralysis 
 
 
 
 
 - Nasal hemorrhage 
 
 
 
 
 - Localized skin fibrosis, edema, and/or ulceration 
 
 
 
 
 - Radiation-induced malignancy (ex. Fibrosarcoma) 
 
 
 
 
 
10.2 Minimization of Risks 
 
 
Although the risks outlined in Section 9.3 may occur, the likelihood of serious events  
 
 
occurring is considered uncommon as long as certain precautions are taken.  The potential  
 
 
risks have been minimized by strict compliance with normal tissue dose constraints as  
 
 
described in Sections 6.3. 
 
 
10.3 Potential Patient Benefits 
 
 
10.3.1 Ability to offer effective aggressive local therapy to patients with recurrent  
 
 
 
unresectable head and neck cancers who have received prior wide-field radiation 
 
 
10.3.2 Reduction in amount of radiation delivered to adjacent normal structures 
 
 
10.3.3 Reduced treatment duration compared to standard-fractionation radiation therapy 
 
 
10.4 Justification of the Study 
 
 
Patients who have locally recurrent or persistent malignant head and neck cancer after  
 
 
definitive conventionally fractionated radiation therapy pose a therapeutic challenge since  
 
 
complete surgical resection is often not feasible and surrounding critical normal tissues have  
 
 
typically received close to maximum tolerable radiation doses.   High dose, precisely targeted  
 
 
radiation with stereotactic body radiotherapy, which delivers minimal additional radiation dose  
 
 
to nearby normal tissues can produce durable local control and palliation of local symptoms  
 
 
such as pain.  In addition, some benign head and neck tumors which are located near the skull  
 
 
base and/or involve critical vasculature also pose a surgical challenge.  These tumors appear to  
 
 
have a reasonably high local control probability with radiation therapy.  SBRT is  
 
 
advantageous in this setting by limiting the dose to adjacent normal tissues in patients who  
 
 
otherwise have a long life expectancy. 
 
 
10.5 Statistical Analysis 
 
 
10.5.1 The overall survival and local control rates will be analyzed. 
 
 
10.5.2 The incidence rate for any serious adverse events will be calculated. 
 

Amendment 2: February 4, 2013 
11 
11.0 References 
 
(1) Cmelak AJ, Cox RS, Adler JR. et al. Radiosurgery for skull base malignancies and nasopharyngeal 
carcinoma.  Int J Radiat Oncol Biol Phys 1997;37:997-1003.  
 
(2)   Kocher M, Voges J, Starr S, et al. Linear accelerator radiosurgery for recurrent maliganant tumors of 
the skull base. Am J Clin Onc (CCT) 1998;21:18-22 
 
(3)  Chua DTT, Sham JST, Nung KN et al. Sereotactic radiosuregry as a salvage treatment for locally 
persistent and recurrent nasopharyngeal cancinoma.  Head Neck 1999;21:620-626.  
 
(4) Chen HJ, Leung SW, Su CY. Linear accelerator based radiosuregry as a salvage treatment for skull 
base and intracranial invasion of recurrrent nasopharyngeal carcinoma.  Am J Clin Oncol (CCT) 
2001;24:255-258.   
 
(5)   Chua DTT, Sham JST, Hung KN et al. Salvage treatment for persisitent and recurrent T1-2 
nasopharygeal carcinoma by stereotactic radiosuregry. Head Neck 2001;23:791-798. 
 
(6) Wu S, Chua, DTT, Deng M et al. Outcome of fractionated stereotactic radiotherapy for 90 patients 
with locally persistent and recurrent nasopharygeal carcinoma.  Int J Radiat Oncol Biol Phys 
2007;69:761-769.  
 
 
(7)    Helen HWC, Sen-Tien T, Mei-Shu W et al. Experience in fractionated stereotactic body radiation 
therapy boost for newly diagnosed nasopharyngeal carcinaoma.  Int J Radiat Onc Biol Phys 2006; 
66:1408-1414 
 
(8)   Quynh-Thu L, Tate D, Koong A, et al.  Improved local control with stereotactic radiosurgical boost 
in patients with nasopharyngeal carcinoma. Int J Radiat Onc Biol Phys 2003;56:1046-1054 
 
(9)   Voynov G, Heron DE, Burton S et al. Frameless stereotactic radiosurgery for recurrent head and 
neck cancer. Technol Cancer Res Treat 2006;5:529-35,  
 
(10)  Oda K, Mori Y, Kobayashi T et al.  Stereotactic radiosurgery as a salvage treatment for recurrent 
epipharygeal carcinoma.  Stereotactic  Funct Neorosurg 2006;84:103-8.   
 
(11)  Ryu S, Khan M, Yin FF:  Image-Guided Radiosurgery of head and neck cancers.  Otolaryngol Head 
Neck Surg 2004;130: 690-7 
 
(12) Martin J, Niranjan A, Kondziolka et al.  Radiosurgery for chordomas and chondrosarcomas of the 
skull base.  J Neurosurgery 107; 758-764, 2007)  
 
(13)Kondziolka D, Lunsford LD, Flickinger JC: The role of radiosuregry in the management of chordoma 
and chondrosarcoma of the cranial base. Neurosurgery 29; 38-46, 1991.   
 
(14)Krishan S, Foote RL, Brown PD: Radiosurgery for cranial base chordoma and chrondrosarcomas. 
Neurosurgery 56; 777-784, 2005.   
 
(15)Muthukumar N, Kondziolka D, Lunsford LD et al. Stereotactic radiosurgery for chordoma snd 
chrondrosarcoma: futher experience. Int J Radiol Biol Phys 41:387-392,1998.) 
 
 

Amendment 2: February 4, 2013 
12 
12.0 Appendices 
 
 
12.1 Appendix I 
 
St. John’s Mercy Medical Center 
Informed Consent for a Clinical Research Study 
 
STUDY TITLE: 
PHASE IV TRIAL TO USE STEREOTACTIC BODY RADIOTHERAPY (SBRT) FOR  
 
HEAD AND NECK TUMORS 
 
This is a clinical trial (type of research study).  Clinical trials include only patients who choose to take 
part.  This consent form may contain words that you do not understand.  Please ask the study doctor or the 
study staff to explain any words or information that you do not clearly understand.  You may take home 
an unsigned copy of this consent form to think about or discuss with family and friends before making 
your decision.   
 
WHAT SHOULD YOU KNOW ABOUT THE RESEARCH DOCTOR? 
 
You should know that your relationship with a research doctor is different from your relationship with 
your personal doctor.  Your personal doctor is treating your specific problem with the hope of a benefit 
for you.  When a doctor is your research doctor, he/she is treating all subjects under a specific protocol to 
learn about the results of a treatment, and with the understanding that you may or may not benefit from 
your participation in the study.  Be sure to ask questions of the study doctor if you want more information 
about this relationship. 
 
WHY IS THIS STUDY BEING PERFORMED? 
 
Some head and neck cancers recur locally even after aggressive surgery and/or several weeks of daily 
radiation therapy, with or without chemotherapy.  They often cause significant pain or other troublesome 
local symptoms such as difficulty eating.  These are very often not resectable due to nearby critical 
normal tissues such as major blood vessels and nerves.  The ability to give additional radiation using 
standard methods is also very limited since there is a maximum dose that normal tissues can tolerate 
before sustaining permanent injury.  Similarly, some benign head and neck tumors which are located near 
the skull base and/or involve major blood vessels or nerves may also not be easily removed without a 
high risk for permanent tissue injury.   
 
Recent technological advancements now make it possible to deliver high doses of precisely targeted 
radiation directly to tumors, while giving very low doses of radiation to nearby normal tissues.  This 
technology is called stereotactic body radiotherapy.  A similar technology, termed stereotactic 
radiosurgery, has been used for many years to successfully treat malignant and benign tumors in the brain.  
More recently, several institutions have reported successful treatment of both malignant and benign 
tumors that begin in the upper aerodigestive tract and neck.  The purpose of this study is to collect 
additional data on the effectiveness of stereotactic body radiotherapy for unresectable skull base tumors 
and locally recurrent head and neck cancer.   
 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY? 
 
Approximately 50 people are expected to participate in this clinical study. 
 
WHAT IS INVOLVED IN THE STUDY? 
 

Amendment 2: February 4, 2013 
13 
If you wish to take part in this study, a series of tests will be performed to determine if you qualify for 
participation in the clinical study.  Your physician will ask you a series of questions regarding your 
medical history and a standard physical exam will be performed.  If you are a woman of childbearing age, 
you may be asked to give a urine or blood specimen so that a pregnancy test can be performed.  
 
If you qualify for the study, you will undergo a radiation treatment planning session called a simulation.  
At this visit, a custom mask and bite block device will be fabricated or a stereotactic frame will be placed 
to immobilize your head in the correct position for treatment.  Permanent small tattoos may be applied to 
your skin to aid in positioning your body on the treatment table. 
 
There may be several days between the simulation and the day you begin radiation.  During this time, 
complex radiation treatment planning will be performed by your radiation oncologist and their medical 
physics staff.  You will receive between 1-5 radiation treatments.  Your physician will explain your 
treatment in more detail.  Each radiation session may take an hour or longer to complete.  After the entire 
radiation course is complete, you will be given follow-up instructions.    
 
HOW LONG WILL I BE IN THE STUDY? 
 
We anticipate that you will remain in the study for approximately 5 years.  After treatment is completed 
routine follow-up visits will be conducted, typically at 3 month intervals for the first year, then less 
frequently. 
 
Your physician may decide stop your treatment if: 1) your disease becomes worse, or 2) side effects 
become very severe, or 3) new scientific developments occur that indicate the treatment is not in your best 
interest, or 4) your physician believes that this treatment is no longer in your best interest.  If your 
treatment is stopped, your doctor will discuss further treatment options with you.  
 
WHAT ARE THE RISKS OF THE STUDY? 
 
By participating in this study, you are at risk for several possible expected and unexpected side effects 
associated with stereotactic radiotherapy to the Head and Neck.  Some of these are described below; 
however, there also may be other side effects that we cannot predict.  Most side effects go away shortly 
after the radiation therapy is stopped, but in some cases side effects can be serious, long-lasting, or 
permanent.  
 
Risks arising from the delivery of stereotactic radiotherapy to the head and neck which may occur shortly 
after completing treatment may include, but are not limited to:  
 
 
- Generalized fatigue 
 
 
- Nausea and/or vomiting 
 
 
- Loss of appetite 
 
 
- Hair loss over the treatment area 
 
 
- Skin redness and/or tanning over the treatment area 
 
 
- Dry and/or moist skin peeling of skin over the treatment area 
 
 
- Dry itchy skin 
 
 
- Thickened saliva and/or dry mouth 
 
 
- burning sensation with swallowing 
 
 
- Change in taste 
 
 
- Inflammation of the outer ear canal and/or inner ear  
 
 
- Inflammation of the mastoid bone behind the ear 
 
 
- Pain and ulcers in the mouth and/or throat  
 
 
- Sore throat which could lead to weight loss 

Amendment 2: February 4, 2013 
14 
 
 
- Dizziness 
 
Risks arising from the delivery of stereotactic radiotherapy to the head and neck which may develop 
several months to years after completing treatment may include, but are not limited to:  
 
 
- Radionecrosis/Injury of the temporal bone, skull base, mandible 
 
 
- Radionecrosis/Injury of brain tissue 
 
 
- Soft tissue necrosis/damage 
 
 
- Stroke 
 
 
- Cranial nerve neuropathy/damage 
 
 
- Hearing loss 
 
 
- Vocal cord paralysis 
 
 
- Nasal hemorrhage/bleeding 
 
 
- Localized skin hardening, thickening, swelling, and/or ulceration 
 
 
- Radiation-induced cancer (ex. Fibrosarcoma) 
 
 
- Low thyroid gland function 
 
I understand that all these side effects are possible.  I may experience no side effects, some of them, or 
most of them.  Although I will be closely monitored, not all side effects can be predicated and unforeseen 
problems can arise.  I understand that there may be some unknown or unanticipated risks or discomforts 
in addition to those specified here. 
 
Reproductive risks:  Because even very small doses of radiation can affect an unborn baby, you should 
not become pregnant while receiving radiation treatment.  You should also not nurse a baby while 
receiving radiation treatment.  
    
ARE THERE BENEFITS TO TAKING PART IN THE STUDY? 
 
If you agree to take part in this study, there may or may not be a direct medical benefit to you.  However, 
there have been several trials completed at other institutions that have shown high local control rates after 
stereotactic body radiotherapy for haed and neck cancer.  It is also convenient, requiring only 1-5 
radiation sessions and no anesthesia or hospitalization.  Toxicity risk has been reported to be fairly low. 
 
WHAT OTHER OPTIONS ARE THERE? 
 
Other treatment options may include chemotherapy, standard-fractionation radiation therapy, or other 
investigational procedures or medications.  Another option is no further therapy.  Your doctor can provide 
information about your disease and the benefits of the different treatments for you.  You should feel free 
to talk with your doctor about your disease and expected outcomes.  The doctor involved in your care will 
be available to answer any questions you have about this program.  You are free to ask your doctor any 
questions concerning this program now or in the future.  
 
You are free to seek care from a doctor of your choice at any time.  If you do not take part in, or withdraw 
from, the study you will continue to receive alternate care.   
 
WHAT ABOUT CONFIDENTIALITY? 
 
Efforts will be made to keep your personal information confidential.  We cannot guarantee absolute 
confidentiality.  This Informed Consent and another document called an “Authorization to Use and 
Disclose Health Information” control how your health information may be used and disclosed during and 
after this study.  The results of this study may be published or presented at meetings but will not include 
your name or reveal your identity.  To participate in this study, you must sign both the Informed Consent 

Amendment 2: February 4, 2013 
15 
and the Authorization to Use and Disclose Health Information.  Your personal information may be 
disclosed if required by law. 
 
WHAT ARE THE COSTS? 
 
Taking part in this study may lead to added costs to you or your insurance carrier.  Specifically, you or 
your insurance carrier will be responsible for the costs of the baseline blood tests, diagnostic imaging 
studies, stereotactic radiotherapy planning and delivery, and follow-up visits which would otherwise be a 
standard part of your care.  Please ask about any expected added costs or insurance problems.  St. John’s 
Mercy Medical Center has personnel that can assist you with this.   
 
Every precaution will be taken to prevent any injury to you during the study. In the event that injury 
occurs as a result of this study, treatment will be available.  You or your insurance carrier will be 
responsible for the costs of the treatment.  No funds have been set aside for compensation in the event of 
a research related injury.   
 
You or your insurance company will be charged for continuing medical care and/or hospitalization.   
 
You will not receive payment for participating in this study.   
 
WHAT ARE MY RIGHTS AS A PARTICIPANT? 
 
Your participation is voluntary.  You may choose not to take part or may leave the study at any time.  
Your choice will not affect your doctors from providing care to you.  Choosing not to participate or 
leaving the study will not result in any penalty or loss of benefits to which you are entitled. 
 
You will be told of any important new findings developed during the course of your participation in this 
study that may affect your willingness to continue in the study.  The investigator may withdraw you from 
this study if issues occur that show that you should not continue to participate. 
 
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?    
 
If you have any questions or concerns regarding this study, or a research-related injury, you may contact 
one of the Principal Investigators, Dr. Robert Frazier at 314-251-6844 or Dr. Bethany Sleckman at 314-
251-7057 
 
For questions about your rights as a research participant, contact Dr. Donald York, Chairman of the St. 
John’s Mercy Medical Center Institutional Review Board (which is a group of people who review the 
research to protect your rights), at 314-251-6453. 
 
Your doctor understands the importance of your contribution to clinical studies that attempt to improve 
medical care.  Your doctor will make every effort to minimize, control, and treat any problems that may 
happen as a result of your participation in this study.  If you believe that you are injured solely as a result 
of the study, or if you have questions regarding the study, please contact the Principal Investigator. 
 
WHERE CAN I GET MORE INFORMATION? 
 
You may call the NCI’s Cancer Information Service at 1-800-422-6237 or TTY:1-800-322-8615 
 
Visit the NCI’s Web Sites: 
• 
Cancer Trials: comprehensive clinical trials information 

Amendment 2: February 4, 2013 
16 
 
http://cancertrials.nci.nih.gov 
• 
CancerNet: accurate cancer information including PDQ 
 
http://cancernet.nci.nih.gov 
 
SIGNATURES 
 
I have read all the above, asked questions, and received answers concerning areas I did not understand.  I 
have had the opportunity to take this consent form home for review or discussion.  I willingly give my 
consent to participate in this study.  Upon signing this form I will receive a copy.  I may also request a 
copy of the protocol (full study plan). 
 
Participant (sign) ______________________________________________________________ 
 
Participant (written) ___________________________________________________________ 
 
Date _________________________________________________________________________ 
 
Principal Investigator ___________________________________________________________ 
 
Staff Member Performing Consent Process _________________________________________ 
 
Witness _______________________________________________________________________ 
 
IRB Stamp (This form is INVALID if the stamp is not present.) 

Amendment 2: February 4, 2013 
17 
12.2 
Appendix II  
 
 
KARNOFSKY PERFORMANCE SCALE 
 
 
 
100 
Normal; no complaints; no evidence of disease 
 
 
 
90 
Able to carry on normal activity; minor signs or symptoms of disease 
 
 
 
80 
Normal activity with effort; some signs or symptoms of disease 
 
 
 
70 
Cares for self; unable to carry on normal activity or do active work 
 
 
 
60 
Requires occasional assistance, but is able to care for most personal needs 
 
 
 
50 
Requires considerable assistance and frequent medical care 
 
 
 
40 
Disabled; requires special care and assistance 
 
 
 
30 
Severely disabled; hospitalization is indicated, although death not imminent 
 
 
 
20 
Very sick; hospitalization necessary; active support treatment is necessary 
 
 
 
10 
Moribund; fatal processes progressing rapidly 
 
 
 
0 
Dead 
 
 
 
ZUBROD PERFORMANCE SCALE 
 
 
 
0 
Fully active, able to carry on all pre-disease activities without restriction 
 
 
 
(KPS 90-100) 
 
 
 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out  
 
 
 
work of a light or sedentary nature.  For example, light housework, office work 
 
 
 
(KPS 70-80) 
 
 
 
2 
Ambulatory and capable or all self-care but unable to carry out any work  
 
 
 
activities.  Up and about more than 50% of waking hours  
 
 
 
(KPS 50-60) 
 
 
 
3 
Capable of only limited self-care, confined to bed or chair 50% of more of  
 
 
 
waking hours 
 
 
 
(KPS 30-40) 
 
 
 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or  
 
 
 
chair 
 
 
 
(KPS 10-20) 
 

Amendment 2: February 4, 2013 
18 
 
12.3 Appendix III 
 
Common Terminology Criteria for Adverse Events v3.0 (CTCAE) 
 
 
GRADE 
Toxicity 
1 
2 
3 
4 
5 
 
CONSTITUTIONAL 
 
 
 
 
 
 
Fatigue 
Mild fatigue over baseline 
Moderate or causing 
difficulty performing 
some ADL 
Severe fatigue interfering 
with ADL 
Disabling 
- 
Fever 
100.4-102.2°F 
102.3-104.0°F 
> 104.0°F for < 24 hr 
> 104.0°F for > 24 
hr 
Death 
Weight loss 
5 - < 10% of baseline 
10 - < 20% of baseline 
> 20% of baseline; tube 
feeding or TPN indicated 
- 
- 
 
PAIN 
 
 
 
 
 
 
Pain due to radiation 
Mild pain not interfering 
with function 
Moderate pain: pain or 
analgesics interfering 
with function, but not 
interfering with ADL 
Severe pain: pain or 
analgesics severely 
interfering with ADL 
Disabling 
- 
Myositis 
(inflammation or 
damage of muscle) 
Mild pain not interfering 
with function 
Pain interfering with 
function, but not 
interfering with ADL 
Pain interfering with 
ADL 
Disabling 
Death 
 
SKIN 
 
 
 
 
 
 
Radiation dermatitis 
Faint erythema or dry 
desquamation 
Moderate to brisk 
erythema; patchy moist 
desquamation, mostly 
confined to skin folds and 
creases; moderate edema 
Moist desquamation 
other that skin folds and 
creases; bleeding induced 
by minor trauma or 
abrasion 
Skin necrosis or 
ulceration of full 
thickness dermis; 
spontaneous 
bleeding from 
involved site 
 
Telangiectasia 
Few 
Moderate number 
Many and confluent 
- 
- 
Ulceration 
- 
Superficial ulceration < 2 
cm size; local wound 
care; medical intervention 
indicated 
Ulceration > 2 m size; 
operative debridement, 
primary closure or other 
invasive intervention 
indicated (ex. Hyperbaric 
oxygen) 
Life-threatening 
consequences; 
major invasive 
intervention (ex. 
Complete resection, 
tissue 
reconstruction, flap, 
grafting) 
Death 
Induration 
Increased density on 
palpation 
Moderate impairment of 
function not interfering 
with ADL; marked 
increase in density and 
firmness on palpation 
with or without minimal 
retraction 
Dysfunction interfering 
with ADL; ery marked 
density, retraction or 
fixation 
- 
- 
 
SOFT TISSUE 
 
 
 
 
 
 
Fibrosis 
Increased density, 
“ spongy” feel 
Increased density with 
firmness or tethering 
Increased density with 
fixation of tissue; 
operative intervention 
indicated; interfering 
with ADL 
Life-threatening; 
disability; loss of 
limb; interfering 
with vital organ 
function 
Death 
Soft Tissue Necrosis 
- 
Local wound care; 
medical intervention 
indicated 
Operative debridement or 
other invasive 
intervention indicated 
(ex. Hyperbaric oxygen) 
Life-threatening 
consequences; 
major invasive 
intervention 
indicated (ex. 
Tissue 
reconstruction, flap, 
or grafting) 
Death 

Amendment 2: February 4, 2013 
19 
Osteonecrosis 
Asymptomatic, 
radiographic findings only 
Symptomatic and 
interfering with function, 
but not interfering with 
ADL; minimal bone 
removal indicated (minor 
sequestrectomy) 
Symptomatic and 
interfering with ADL; 
operative intervention or 
hyperbaric oxygen 
indictaed 
Disabling 
Death 
 
AUDITORY/EAR 
 
 
 
 
 
 
Hearing 
_ 
Hearing loss not requiring 
hearing aid or 
intervention (i.e., not 
interfereing with ADL) 
Hearing loss requiring 
hearing aid or 
intervention (i.e., 
interfereing with ADL) 
Profound bilateral 
hearing loss (>90 
dB) 
- 
Otitis, external ear 
(non-infectious) 
External otitis with 
erythema or dry 
desquamation 
External otitis with moist 
desquamation, edema, 
enhanced cerumen, or 
discharge; tympanic 
membrane perforation; 
tympanostomy 
External otitis with 
mastoiditis; stenosis or 
osteomyelitis 
Necrosis of soft 
tissue or bone 
Death 
Otitis, middle ear 
(non-infectious) 
Serous otitis 
Serous otitis, medical 
intervention indicated 
Otitis with discharge; 
mastoiditis 
Necrosis of canal 
soft tissue or bone 
Death 
 
GI TRACT 
 
 
 
 
 
 
Dental, periodontal 
disease 
Gingival recession or 
gingivitis; limited to 
bleeding on probing; mild 
local bone loss 
Moderate ginival 
recession or gingivitis; 
multiple sites of bleeding 
on probing; moderate 
bone loss 
Spontaneous bleeding; 
severe bone loss with or 
without tooth loss; 
osteonecrosis of maxilla 
or mandible 
- 
- 
Dental, teeth 
Surface stains, dental 
caries; restorable, without 
extractions 
Less than full mouth 
extractions; tooth fracture 
or crown amputation or 
repair indicated 
Full mouth extractions 
indicated 
- 
- 
Xerostomia 
Symptomatic (dry or thick 
saliva) without significant 
dietary alteration; 
unstimulated saliva flow > 
0.2 ml/min 
Symptomatic and 
significant oral intake 
alteration (e.g.; copious 
water, other lubricants, 
diet limited to purees and 
/or soft, moist foods) 
unstimulated saliva flow 
0.1 to 0.2 ml/min 
Symptoms leading to 
inability to adequately 
aliment orally; IV fluids, 
tube feedings, or TPN 
indicated; unstimulated 
saliva <0.1 ml/min 
- 
- 
Nausea 
Loss of appetite without 
alteration in eating habits 
Oral intake decreased 
without significant weight 
loss, dehydration, or 
malnutrition; IV fluids 
indicated < 24 hr 
Inadequate oral caloric or 
fluid intake; IV fluids, 
tube feedings, or TPN 
indicated > 24 hr 
Life-threatening 
consequences 
Death 
Vomiting 
1 episode in 24 hr 
2-5 episodes in 24 hr; IV 
fluids indicated < 24 hr 
> 6 episodes in 24 hr; IV 
fluids or TPN indicated > 
24 hr 
Life-threatening 
consequences 
Death 
Dysphagia 
Symptomatic, able to eat 
regular diet 
Symptomatic, and altered 
eating/swallowing (e.g., 
altered dietary habits, oral 
supplements); IV fluids 
indicated < 24 hours 
Symptomatic, and 
severely altered 
eating/swallowing (e.g., 
inadequate oral caloric or 
fluid intake); IV fluids, 
tube feedins, or TPN  
indicated ≥ 24 hours 
Life-threatening 
consequences (e.g./ 
obstruction, 
perforartion) 
Death 
Mucositis 
(clinical exam) 
Erythema of the mucosa 
Patchy ulcerations or 
pseudomembranes 
Confluent ulcerations or 
pseudomembranes; 
bleeding with minor 
trauma 
Tissue necrosis; 
significant 
spontaneous 
bleeding; life 
threatening 
consequences 
Death 
Esophagitis 
 
Asymptomatic, 
pathologic,radiographic or 
endoscopic findings only 
Symptomatic; altered 
eating/swallowing (e.g. 
altered dietary habits, oral 
supplements) IV fluids 
indicated < 24 hours 
Symptomatic and severly 
altered eating/swallowing 
(e.g. inadequate oral 
caloric or fluid intake) IV 
fluids, tube feedings, or 
TPN indicated ≥ 24 hours 
Life-threatening 
consequences 
Death 
Ulceration 
Asymptomatic, 
Symptomatic; altered GI 
Symptomatic and 
Life-threatening 
Death 

Amendment 2: February 4, 2013 
20 
radiographic or endoscopic 
findings only 
function (altered dietary 
habits, oral supplements); 
IV fluids indicated < 24 
hr 
severely altered GI 
function (inadequate oral 
caloric or fluid intake); 
IV fluids, tube feedings, 
or TPN indicated > 24 hr 
consequences 
Bleeding 
Mild, intervention (other 
than iron supplements) not 
indicated 
Symptomatic and medical 
intervention or minor 
cauterization indicated  
Transfusion, 
interventional radiology, 
endoscopic, or operative 
intervention indicated 
Life-threatening 
consequences; 
major urgent 
intervention 
indicated 
Death 
Perforation 
Asymptomatic radiographic 
findings only 
Medical intervention 
indicated; IV fluids 
indicated < 24 hr 
IV fluids, tube feedings, 
or TPN indicated > 24 hr; 
operative intervention 
indicated 
Life-threatening 
consequences 
Death 
Stricture 
Asymptomatic radiographic 
findings only 
Symptomatic; altered GI 
function (altered dietary 
habits, vomiting, 
bleeding, diarrhea); IV 
fluids indicated < 24 hr 
Symptomatic and 
severely altered GI 
function (altered dietary 
habits, diarrhea, or GI 
fluid loss); IV fluids, 
tube feedings, or TPN 
indicated > 24 hr; 
operative intervention 
indicated 
Life-threatening 
consequences; 
operative 
intervention 
requiring complete 
organ resection 
Death 
Fistula 
Asymptomatic; 
radiographic findings only 
Symptomatic; altered GI 
function (ex. Altered 
dietary habits, diarrhea, or 
GI fluid loss); IV fluids 
indicated < 24 hr 
Symptomatic and 
severely altered GI 
function (ex. Altered 
dietary habits, diarrhea, 
or GI fluid loss); IV 
fluids, tube feedings, or 
TPN indicated > 24 hr 
Life-threatening 
consequences 
Death 
Taste Alterations 
Altered taste but no change 
in diet 
Altered taste with chage 
in diet (e.g.; oral 
supplements); noxious or 
unpleasant taste; loss of 
taste 
- 
- 
- 
 
LYMPHATICS 
 
 
 
 
 
 
Lymphatics (head 
and neck) 
Localized to dependant 
areas, no disability or 
functional impairment 
Localized facial or neck 
edema with functional 
impairment 
Generalized facial or 
neck edema with 
functional impairment 
(e.g.; difficulty in turning 
neck or opening mouth 
compared to baseline) 
Severe with 
ulceration or 
cerebral edema; 
tracheotomy or 
feeding tube 
Death 
 
NEUROLOGY 
 
 
 
 
 
 
Brachial plexopathy 
Asymptomatic 
Symptomatic, not 
interfering with ADL 
Symptomatic, interfering 
with ADL 
Disabling 
Death 
CNS Necrosis 
Asymptomatic, 
radiographic findings only 
Symptomatic, not 
interfering with ADL; 
medical intervention 
indicated 
Symptomatic and 
interfering with ADL; 
hyperbaric oxygen 
indicated 
Life-threatening; 
disabling; operative 
intervention 
indicated to prevent 
or treat CNS 
necrosis/cystic 
progression 
Death 
Myelitis 
Asymptomatic, mild signs 
(e.g.; Babinski’s or 
Lhermitte’s sign) 
Weakness or sensory loss 
not interfering with ADL 
Weakness or sensory loss 
interfering with ADL 
Disabling 
Death 
 
OCULAR/VISUAL 
 
 
 
 
 
 
 
 
Cataract 
 
 
 
Asymptomatic, detected 
only on exam 
Symptomatic, with 
moderate decrease in 
visual acuity (20/40 or 
better); decreased visual 
function correctable with 
glasses 
Symptomatic with 
marked decrease in 
visual acuity (worse than 
20/40); operative 
intervention indicated 
(e.g.; cataract surgery) 
- 
- 
Dry eye syndrome 
Mild, intervention not 
Symptomatic, interfering 
Symptomatic or decrease 
- 
- 

Amendment 2: February 4, 2013 
21 
indicated 
with function but not 
interfering with ADL; 
medical intervention 
indicated 
in visual acuity  
interfering with ADL; 
operative intervention 
indicated 
Rentinopathy 
Asymptomatic 
Symptomatic, with 
moderate decrease in 
visual acuity (20/40 or 
better) 
Symptomatic with 
marked decrease in 
visual acuity (worse than 
20/40) 
Blindness  
(20/200 or worse 
- 
 
SECONDARY 
MALIGNANCY 
 
- 
- 
Non-life-threatening 
basal or squamous cell 
carcinoma of the skin 
Solid tumor, 
leukemia, or 
lymphoma 
Death 
 
 

Amendment 2: February 4, 2013 
22 
 
12.4 Appendix IV 
 
DEMOGRAPHIC FORM – Page 1 of 1 
 
 
1.  Name ____________________(last)   ____________________(first)    
 
2.  Date of Birth  ____/____/__________ 
 
3. RT Number ____________________ 
 
4.  Race: 
 Asian 
 Caucasian 
 Black 
 Other, specify _______________________ 
 
 
5.  Zubrod PS:  
 0 
 1 
 2 
 3 
 
6. Radiation oncologist:  __________________________________ 
 
7. Medical oncologist:  ___________________________________ 
 
8.  Surgeon:  ___________________________________________ 
 
9. Tumor category:  
 Benign Head and Neck tumor, specify type __________ 
 
 
 
 
 
 
 
 Malignant Head and Neck Tumor, specify type __________ 
 
 
 
 
10. Maximum tumor diameter:  _______ cm   
 
 
11. AJCC Staging Classification: 
 I 
 II 
 III 
 IV  
 N/A (recurrence) 
 
12. Status of distant metastatic disease: 
 No distant metastatic disease 
 
 
 Stable distant metastatic disease 
 
 
 Progressive metastatic disease 
 
13.  Pretreatment CT scan: 
Date of CT scan __________ 
 
 
 
 
14.  Prior Head and Neck radiation: 
 No 
 Yes, explain  ______________________________ 
 
15.  Pre-SBRT chemotherapy: 
 No 
 
 
 Yes, regimen & last cycle date _______________________________________ 
 
 
Person completing form :  Signature _________________________     Print Name __________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 

Amendment 2: February 4, 2013 
23 
12.5 
Appendix V 
 
TREATMENT FORM – Page 1 of 1 
 
 
1.  Name ____________________(last)   ____________________(first)    
 
2. RT Number ____________________ 
 
3.  Tumor Details:   
 
Tumor category:  
 Benign Head and Neck tumor, specify type __________  
 
 
 
 
 
 
 Malignant Head and Neck Tumor, specify type __________ 
 
 
Lesion # 
 
Location 
Maximum  
Diameter  
(cm) 
GTV  
Volume  
(cc) 
CTV  
Margin  
(cm) 
PTV  
Margin  
(cm) 
PTV  
Volume  
(cc) 
 
 
 
 
 
AP 
RL 
CC 
 
1 
 
 
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
 
5 
 
 
 
 
 
 
 
 
 
4. Treatment Portal Design: 
 
 
 Static gantry angle (coplanar), specify number of fields __________ 
 
 
 Static gantry angle (non-coplanar), specify number of fields __________ 
 
 
 Dynamic arc (coplanar), specify number of arcs __________ 
 
 
 Dynamic arc (non-coplanar), specify number of arcs __________ 
 
5. Dose-Fractionation Scheme:  
Lesion # 
Total Dose  
(Gy) 
Dose per Fx  
(Gy) 
# Fx 
Prescription  
IDL (%) 
Dmax 
(Gy) 
BEDα/β=10 
(Gy) 
BEDα/β=3 
(Gy) 
CI 
1 
 
 
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
 
5 
 
 
 
 
 
 
 
 
 
 
6.  Dose to Normal Tissues: 
 
 
Prior Head and Neck radiation: 
 No (Table 1) 
 Yes (Table 2) 
 
 
 
 
Table 1 (No prior Head and Neck radiation) 
 
Normal Tissue 
Dmax (Gy) 
Optic Chiasm 
 
Optic Nerve 
 
Brainstem 
 
Spinal Cord 
 
Brachial Plexus 
 

Amendment 2: February 4, 2013 
24 
Internal Carotid Artery  
in Cavernous Sinus 
 
Oculomotor Nerves in 
Cavernous Sinus 
 
Esophagus 
 
Skin 
 
 
 
 
 
 
Table 2 (Prior Head and Neck radiation) 
 
 
 
Normal Tissue 
 
Dmax (Gy) 
 
Prior RT Dmax  
(Gy)* 
 
 
Total Dmax (Gy) 
(Dmax + Prior RT Dmax) 
Optic Chiasm 
 
 
 
Optic Nerve 
 
 
 
Brainstem  
 
 
 
Spinal Cord 
 
 
 
Brachial Plexus 
 
 
 
Internal Carotid Artery  
in Cavernous Sinus 
 
 
 
Oculomotor Nerves in 
Cavernous Sinus 
 
 
 
Esophagus 
 
 
 
Skin 
 
 
 
 
 
*Estimation of the dose (Gy) may be required 
 
7. 
Premedication: 
 
 
 None 
 
 
 Anti-nausea, specify drug __________, dose _____ mg,  
 
 
 Decadron, specify dose _____ mg  
 
 
 Analgesics, specify drug __________, dose _____ mg 
 
 
 Acetaminophen, specify dose _____ mg 
 
 
Person completing form :  Signature _________________________     Print Name __________________________ 
 
 
 

Amendment 2: February 4, 2013 
25 
 
12.6 Appendix VI 
 
FOLLOW-UP VISIT FORM – Page 1 of 2 
 
1.  Name ____________________(last)   ____________________(first)    
 
2. RT Number ____________________ 
 
3. Date of Visit:  ____/____/__________ 
 
4.  CT scan date:  ____/____/__________ 
 
5. Radiation Therapy related adverse events 
Adverse Event 
CTC V3.0 
Grade 
Timing  Treatment 
Comments 
ACUTE 
 
 
 
 
 Fatigue  
 
 
 
 
 Fever 
  
 
 
 
 Nausea 
 
 
 
 
 Vomiting  
 
 
 
 
 Loss of appetite 
 
 
 
 
 Weight loss 
 
 
 
 
 Esophagitis 
 
 
 
 
 Alopecia 
 
 
 
 
 Radiation dermatitis 
 
 
 
 
 Musculoskeletal pain 
 
 
 
 
 Mucositis 
 
 
 
 
 Hoarseness 
 
 
 
 
 Pneumonitis 
 
 
 
 
 Xerostomia 
 
 
 
 
 External otitis 
 
 
 
 
 Otitis Media 
 
 
 
 
 Mastoiditis 
 
 
 
 
 Dizzyness 
 
 
 
 
LATE 
 
 
 
 
 Radionecrosis of temporal bone, skull base, mandible 
 
 
 
 
 Radionecrosis of brain tissue 
 
 
 
 
 CVA 
 
 
 
 
 Cranial nerve neuropathy 
 
 
 
 
 Hearing loss 
 
 
 
 
 Vocal cord paralysis 
 
 
 
 
 Nasal hemorrhage 
 
 
 
 
 Hypothyroidism 
 
 
 
 
 Esophageal stricture/perforation 
 
 
 
 
 Brachial plexopathy 
 
 
 
 
 Telangiectasia 
 
 
 
 
 Skin Ulceration 
 
 
 
 
 Skin/SubQ Tissue Fibrosis 
 
 
 
 
 Soft Tissue Necrosis 
 
 
 
 
 Radiation-induced Malignancy 
 
 
 
 
 
5. Serious adverse event?  
 No   
 Yes, submit report to HIC 
 
6. Has systemic therapy been given?  
 No   
 Yes 

Amendment 2: February 4, 2013 
26 
 
If yes, list therapy 
 
Agent(s) 
Start Date 
Stop Date 
 
__________________________ 
____/____/__________ 
____/____/__________ 
 
__________________________ 
____/____/__________ 
____/____/__________ 
 
__________________________ 
____/____/__________ 
____/____/__________ 
 
7. CT scan since last follow-up visit?  
 No   
 Yes, date ____ / ____ / __________ 
 
Tumor Response: 
 Complete response 
 
 
 Partial response 
 
 
 Stable disease 
 
 
 Progressive disease 
 
8. PET/CT scan since last follow-up visit?  
 No   
 Yes, date ____ / ____ / __________ 
 
Tumor Response: 
 Complete response 
 
 
 Partial response 
 
 
 Stable disease 
 
 
 Progressive disease 
 
8. Disease Status  
 
 No evidence of tumor 
Date of Diagnosis 
 
 Local recurrence within the treatment volume 
____/____/_________ 
 
 
 Progressive liver disease outside the treatment volume 
____/____/_________ 
 Distant recurrence, specify site _______________________ 
____/____/_________ 
 
9. Additional treatment for recurrent disease  
 
Surgical excision 
 Yes  
 No   
Date of surgery ____/____/_________ 
 
Chemotherapy, agents ___________________ 
 Yes  
 No   
Start date ____/____/_________ 
 
Other, specify _________________________ 
 Yes  
 No   
Start date ____/____/_________ 
  
10. Death?   
  No   
 Yes, date ____/____/__________  Cause? ____________________________ 
 
 
Person completing form :  Signature _________________________     Print Name __________________________