eligibility checklist -step 2 (10/17/13)
references (10/17/13)

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Vineberg KA, Eisbruch A, Coselmon MM, et al. Is uniform target dose possible in IMRT plans in the head and neck? *IJROBP*. 52:1159-72, 2002. Wallace MR, Logan H, et al. HPV in head and neck cancers among 5-year survivors. *Am J Clin Oncol*.  
33(4): 425-6, 2010. Webster GJ, Rowbottom CG, Ho KF, et al. Evaluation of larynx-sparing techniques with IMRT when treating the head and neck. *IJROBP*. 72:617-22, 2008.  
Weismann P, Weismanova E, et al. The detection of circulating tumor cells expressing E6/E7 HR-HPV
oncogenes in pereipheral blood in cervical cancer patients after radical hysterectomy. *Neoplasma*. 56(3):
230-8, 2009.  
West K, Brognard J, et al. Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells." *J Clin Invest*. 111(1): 81-90, 2003.  
Wheeler SE, Suzuki S, et al. Epidermal growth factor receptor variant III mediates head and neck cancer cell invasion via STAT3 activation. *Oncogene*. 29(37): 5135-45, 2010.  
Worden FP, Kumar B, Lee JS, et al. Chemoselection as a strategy for organ preservation in advanced oropharynx cancer: response and survival associated with HPV copy number. *J Clin Oncol*. 26: 3138-46, 2008.  
Yellen SB, Cella DF, Webster K et al. Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system. *J Pain Symptom Manage*.  
13(2): 63-74, 1997.  
Zhang ZF, Morgenstern H, Spitz MR, et al. Marijuana use and increased risk of squamous cell carcinoma of the head and neck. *Canc Epidem Biomarkers Prev.* 8(12): 1071-8, 1999.  
Zuur CL, Simis YJ, Lansdaal PE, et al. Risk factors of ototoxicity after cisplatin-based chemo-irradiation in patients with locally advanced head-and-neck cancer: A multivariate analysis. *IJROBP.* 68(5);1320-1325, 2007.
eligibility checklist -step 2 (10/17/13)
appendix i study parameter table

| Assessments                                                                                                                                                                                                                                                                                                                                                           | Within 8 weeks                                                      | Within 2 weeks   |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------|------------------|
| prior to registration                                                                                                                                                                                                                                                                                                                                                 | prior to registration                                               |                  |
| Eligibility-related tissue collection                                                                                                                                                                                                                                                                                                                                 | Prior to Step 2 registration                                        |                  |
| Smoking history survey (CASI)                                                                                                                                                                                                                                                                                                                                         | Prior to Step 2 registration                                        |                  |
| History                                                                                                                                                                                                                                                                                                                                                               | X                                                                   |                  |
| Rad Onc exam                                                                                                                                                                                                                                                                                                                                                          | X                                                                   |                  |
| Med Onc exam                                                                                                                                                                                                                                                                                                                                                          | X                                                                   |                  |
| ENT or H&N Surgeon exam                                                                                                                                                                                                                                                                                                                                               | X                                                                   |                  |
| Chest imaging                                                                                                                                                                                                                                                                                                                                                         | *X (see Section 11.2.1)                                             |                  |
| Performance Status                                                                                                                                                                                                                                                                                                                                                    | X                                                                   |                  |
| CDC w/diff & ANC                                                                                                                                                                                                                                                                                                                                                      | X                                                                   |                  |
| Total bilirubin; AST or ALT                                                                                                                                                                                                                                                                                                                                           | X                                                                   |                  |
| Creatinine or                                                                                                                                                                                                                                                                                                                                                         |                                                                     | X                |
| Creatinine Clearance  Serum pregnancy test (if                                                                                                                                                                                                                                                                                                                        |                                                                     | X                |
| applicable)  Na, K, Cl, glucose, Ca, Mg,                                                                                                                                                                                                                                                                                                                              | Within 2 weeks prior to treatment                                   |                  |
| albumin  *CD4 count for pts. with known                                                                                                                                                                                                                                                                                                                               | Prior to Step 1 registration                                        |                  |
| HIV  Dental assessment                                                                                                                                                                                                                                                                                                                                                | Within 8 weeks prior to treatment                                   |                  |
| Swallowing eval (Section 4.1.4)                                                                                                                                                                                                                                                                                                                                       | Within 4 weeks prior to treatment                                   |                  |
| Audiogram                                                                                                                                                                                                                                                                                                                                                             | Required: Within 12 weeks prior to treatment                        |                  |
| Whole body PET/CT                                                                                                                                                                                                                                                                                                                                                     | Recommended: Within 8 weeks prior to treatment                      |                  |
| Nutrition/feeding tube eval                                                                                                                                                                                                                                                                                                                                           | *Recommended: Within 2 weeks prior to treatment  See Section 11.2.2 |                  |
| CT or MRI or PET/CT of neck,                                                                                                                                                                                                                                                                                                                                          | X                                                                   |                  |
| with contrast  Adverse event eval                                                                                                                                                                                                                                                                                                                                     | Evaluation of condition prior to treatment                          |                  |
| The QOL component was closed to accrual on 2/28/13 QOL/Functional Assessments –if the patient  consents: QLQ-C30; QLQ-H&N35; EQ-5D; PRO-CTCAE-H&N; Work Status, HHIA-S: Prior to start of  treatment  Risk Factor Survey (CASI) –if the patient consents: Prior to start of treatment  Specimen collection for banking- if the patient consents: Prior to start of tx |                                                                     |                  |
eligibility checklist -step 2 (10/17/13)
appendix i study parameter table

| Assessments                            | Weekly during radiation          | As clinically indicated   |
|----------------------------------------|----------------------------------|---------------------------|
| History                                | *brief history                   | *brief history            |
| Rad Onc exam  Med Onc exam             | X                                |                           |
| Performance Status                     | X                                |                           |
| CDC w/diff & ANC                       | X                                |                           |
| Creatinine or Creatinine               | X                                |                           |
| Clearance  Na, K, Cl, glucose, Ca, Mg, | X                                |                           |
| albumin  Whole body PET/CT             | X                                |                           |
| CT or MRI or PET/CT of neck,           | X                                |                           |
| with contrast  Biopsy                  | If suspicion of tumor recurrence |                           |
| Adverse Event eval                     | X                                | X                         |
eligibility checklist -step 2 (10/17/13)
appendix i study parameter table

| Assessments                                                | At 1 month postXRT                                                       | q3 mos. from end of  RT for 2 yrs; q6 mos.  for 3 yrs; then  annually   | As clinically indicated                 |
|------------------------------------------------------------|-------------------------------------------------------|-------------------------------------------------------------------------|-----------------------------------------|
| History                                                    | brief history                                         | brief history                                                           |                                         |
| Exam by Rad Onc or Med  Onc or ENT or H&N                  | X                                                     | *X                                                                      |                                         |
| Surgeon  Chest imaging                                     | *X                                                    |                                                                         |                                         |
| Performance Status                                         | X                                                     | X                                                                       |                                         |
| CDC w/diff & ANC                                           | X                                                     |                                                                         |                                         |
| Total bilirubin; AST or                                    | X                                                     |                                                                         |                                         |
| ALT  Na, K, Cl, glucose, Ca,                               | X                                                     |                                                                         |                                         |
| Mg, albumin  Dental assessment                             | At 12, 24, 60, and 120  months from end of  treatment |                                                                         |                                         |
| Whole body PET/CT                                          | *X                                                    | X                                                                       |                                         |
| Nutrition/feeding tube eval                                | X                                                     |                                                                         |                                         |
| CT or MRI or PET/CT of                                     |                                                       | *X                                                                      | After 5 years, as clinically  indicated |
| neck, with contrast  Biopsy                                | If suspicion of tumor  recurrence                     |                                                                         |                                         |
| Adverse event eval                                         | X                                                     | X                                                                       | X                                       |
| QOL/Functional  Assessments –if the patient  consented and is one of the  400 accrued to QOL  component (closed to  accrual 2/28/13): QLQ-C30;  QLQ-H&N35; EQ-5D; PROCTCAE-H&N; Work Status,  HHIA-S                                                            | End of treatment                                      | At 3, 6, and 12 months  from end of treatment                           |                                         |
| Specimen collection for  banking- if the patient  consents | At 3 and 6 months from  end of treatment              |                                                                         |                                         |  
0 Fully active, able to carry on all predisease activities without restriction 1 Restricted in physically strenuous activity but ambulatory and able to carry work of a light or sedentary nature. For example, light housework, office work 2 Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours 3 Capable of only limited self-care, confined to bed or chair 50% or more of waking hours 4 Completely disabled. Cannot carry on self-care. Totally confined to bed 5 Death
appendix iii staging system edge
staging-primary tumor (t)

TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ  
| TX                                                                                                                     | Primary tumor cannot be assessed                                                                                                                                                                                                                                                                                                                                                                            |
|------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| T0                                                                                                                     | No evidence of primary tumor                                                                                                                                                                                                                                                                                                                                                                                |
| Tis                                                                                                                    | Carcinoma in situ                                                                                                                                                                                                                                                                                                                                                                                           |
| T1                                                                                                                     | Tumor 2 cm or less in greatest dimension                                                                                                                                                                                                                                                                                                                                                                    |
| T2                                                                                                                     | Tumor more than 2 cm but not more than 4 cm in greatest dimension                                                                                                                                                                                                                                                                                                                                           |
| T3                                                                                                                     | Tumor more than 4 cm in greatest dimension                                                                                                                                                                                                                                                                                                                                                                  |
| T4a                                                                                                                    | Moderately advanced local disease*  (lip) Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or  skin of face (i.e., chin or nose)  (oral cavity) Tumor invades adjacent structures only (e.g., through cortical bone  [mandible or maxilla] into deep [extrinsic] muscle of tongue [genioglossus,  hyoglossus, palatoglossus, and styloglossus], maxillary sinus, skin of face) |
| T4b                                                                                                                    | Very advanced disease  Tumor invades masticator space, pterygoid plates or skull base and/or encases  internal carotid artery                                                                                                                                                                                                                                                                               |
| *Note: Superficial erosion alone of bone/tooth socket by gingival primary is not sufficient to classify a tumor as T4. |                                                                                                                                                                                                                                                                                                                                                                                                             |  
| Maxillary Sinus  T1 Tumor limited to maxillary sinus mucosa with no erosion or destruction of bone  T2 Tumor causing bone erosion or destruction including extension into the hard palate  and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and  pterygoid plates  T3 Tumor invades any of the following: bone of the posterior wall of maxillary sinus,  subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, ethmoid sinuses  T4a Moderately advanced local disease  Tumor invades anterior orbital contents, skin of cheek, pterygoid plates,  infratemporal fossa, cribriform plate, sphenoid or frontal sinuses  T4b Very advanced local disease  Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa,  cranial nerves other than maxillary division of trigeminal nerve (V2), nasopharynx or  clivus    Nasal Cavity and Ethmoid Sinus  T1 Tumor restricted to any one subsite, with or without bony invasion  T2 Tumor invading two subsites in a single region or extending to involve an adjacent  region within the nasoethmoidal complex, with or without bony invasion  T3 Tumor extends to invade the medial wall or floor of the orbit, maxillary sinus, palate,   |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| or cribriform plate   |                                                                                                                                                                                                                                                                                                                                                                   |
|-----------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| T4a                   | Moderately advanced local disease  Tumor invades any of the following: anterior orbital contents, skin of nose or cheek,  minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal  sinuses  Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa,  cranial nerves other than V2, nasopharynx, or clivus |  
| PHARYNX    Nasopharynx  T1                                                    | Tumor confined to the nasopharynx, or tumor extends to oropharynx and/or nasal  cavity with out parapharyngeal extension*                                  |
|-------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------|
| T2                                                                            | Tumor with parapharyngeal extension*                                                                                                                       |
| T3                                                                            | Tumor involves bony structures of skull base and/or paranasal sinuses                                                                                      |
| T4                                                                            | Tumor with intracranial extension and/or involvement of cranial nerves, hypopharynx,  orbit, or with extension to the infratemporal fossa/masticator space |
| *Note: Parapharyngeal extension denotes posterolateral infiltration of tumor. |                                                                                                                                                            |  
| T1   | Tumor 2 cm or less in greatest dimension                                                                                                                                                                                                                       |
|------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| T2   | Tumor more than 2 cm but not more than 4 cm in greatest dimension                                                                                                                                                                                              |
| T3   | Tumor more than 4 cm in greatest dimension or extension to lingual surface of  epiglottis                                                                                                                                                                      |
| T4a  | Moderately advanced local disease  Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate,  or mandible*  Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or  skull base or encases carotid artery |  
Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery *Note: Mucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of larynx.  
| Hypopharynx  T1                                                                                  | Tumor limited to one subsite of hypopharynx and/or 2 cm or less in greatest  dimension                                                                                          |
|--------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| T2                                                                                               | Tumor invades more than one subsite of hypopharynx or an adjacent site, or  measures more than 2 cm but not more than 4 cm in greatest diameter without  fixation of hemilarynx |
| T3                                                                                               | Tumor measures more than 4 cm in greatest dimension or with fixation of hemilarynx  or extension to esophagus                                                                   |
| T4a                                                                                              | Moderately advanced local disease  Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, esophagus or  central compartment soft tissue.*                          |
| T4b                                                                                              | Very advanced local disease  Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal  structures                                                     |
| *Note: Central compartment soft tissue includes prelaryngeal strap muscles and subcutaneous fat. |                                                                                                                                                                                 |  
| LARYNX    Supraglottis  T1                                                                                                                                                                                                                                                                                         | Tumor limited to one subsite of supraglottis with normal vocal cord mobility                                                                                                                                                                                            |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| T2                                                                                                                                                                                                                                                                                                                 | Tumor invades mucosa of more than one adjacent subsite of supraglottis or glottis or  region outside the supraglottis (e.g., mucosa of base of tongue, vallecula, medial wall  of pyriform sinus) without fixation of the larynx                                        |
| T3                                                                                                                                                                                                                                                                                                                 | Tumor limited to larynx with vocal cord fixation and/or invades any of the following:  postcricoid area, pre-epiglottic tissues, paraglottic space, and/or inner cortex of  thyroid cartilage                                                                           |
| T4a                                                                                                                                                                                                                                                                                                                | Moderately advanced local disease  Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx  (e.g., trachea, soft tissues of the neck including deep extrinsic muscle of the tongue,  strap muscles, thyroid, or esophagus)                 |
| T4b                                                                                                                                                                                                                                                                                                                | Very advanced local disease  Tumor invades prevertebral space, encases carotid artery, or invades mediastinal  structures                                                                                                                                               |
| Glottis  T1                                                                                                                                                                                                                                                                                                        | Tumor limited to the vocal cord(s) [may involve anterior or posterior commissure] with  normal mobility                                                                                                                                                                 |
| T1a                                                                                                                                                                                                                                                                                                                | Tumor limited to one vocal cord                                                                                                                                                                                                                                         |
| T1b                                                                                                                                                                                                                                                                                                                | Tumor involves both vocal cords                                                                                                                                                                                                                                         |
| T2                                                                                                                                                                                                                                                                                                                 | Tumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord  mobility                                                                                                                                                                              |
| T3                                                                                                                                                                                                                                                                                                                 | Tumor limited to the larynx with vocal cord fixation, and/or invasion of paraglottic  space, and/or inner cortex of the thyroid cartilage                                                                                                                               |
| T4a                                                                                                                                                                                                                                                                                                                | Moderately advanced local disease  Tumor invades through the outer cortex of the thyroid cartilage and/or invades  tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic  muscle of the tongue, strap muscles, thyroid, or esophagus) |
| T4b                                                                                                                                                                                                                                                                                                                | Very advanced local disease  Tumor invades prevertebral space, encases carotid artery, or invades mediastinal  structures.                                                                                                                                              |
| Subglottis  T1                                                                                                                                                                                                                                                                                                     | Tumor limited to the subglottis                                                                                                                                                                                                                                         |
| T2                                                                                                                                                                                                                                                                                                                 | Tumor extends to vocal cord(s) with normal or impaired mobility                                                                                                                                                                                                         |
| T3                                                                                                                                                                                                                                                                                                                 | Tumor limited to larynx with vocal cord fixation                                                                                                                                                                                                                        |
| T4a                                                                                                                                                                                                                                                                                                                | Moderately advanced local disease  Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx  (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue,  strap muscles, thyroid, or esophagus)                     |
| T4b                                                                                                                                                                                                                                                                                                                | Very advanced local disease  Tumor invades prevertebral space, encases carotid artery, or invades mediastinal  structures.                                                                                                                                              |
| REGIONAL LYMPH NODES (N) Excluding Nasopharynx    NX Regional lymph nodes cannot be assessed  N0 No regional lymph node metastasis  N1 Metastasis in a single ipsilateral node, 3 cm or less in greatest dimension  N2 Metastasis in a single ipsilateral node, more than 3 cm, but not more than 6 cm in greatest |                                                                                                                                                                                                                                                                         |  
101 RTOG 1016, Version Date: 2/23/16  
| dimension, or in multiple ipsilateral lymph nodes, none greater than 6 cm in greatest  dimension, or bilateral or contralateral nodes, none more than 6 cm in greatest dimension                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           |                                                                                                       |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------|
| N2a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        | Metastasis in a single ipsilateral node more than 3 cm, but not more than 6 cm in greatest  dimension |
| N2b                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        | Metastasis in multiple ipsilateral nodes, none more than 6 cm in greatest dimension                   |
| N2c                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        | Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest  dimension      |
| N3                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         | Metastases in a lymph node, more than 6 cm in greatest dimension                                      |
| REGIONAL LYMPH NODES (N) Nasopharynx  NX Regional lymph nodes cannot be assessed  N0 No regional lymph node metastasis  N1 Unilateral metastasis in lymph node(s), 3 cm or less in greatest dimension  N2 Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in  greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest  dimension  N2a Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in  greatest dimension  N2b Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension  N2c Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest  dimension  N3 Metastasis in a lymph node, more than 6 cm in greatest dimension    DISTANT METASTASIS (M)  M0 No distant metastasis  M1 Distant metastasis  MX Distant metastasis cannot be assessed  STAGE GROUPING, Excluding Nasopharynx STAGE GROUPING Nasopharynx  Stage 0 Tis, N0, M0 Stage 0 Tis, N0, M0  Stage I T1, N0, M0 Stage I T1, N0, M0  Stage II T2, N0, M0 Stage II T2, N0, M0  Stage III T3, N0, M0  T1-3, N1, M0    Stage III T1-T3, N1, M0  T3, N0, M0  Stage IVA T4a, N0-1, M0  Stage IVA T4a, N0-2, M0  Any T, N2, M0  T1-3, N2, MO  Stage IVB  T4b, Any N, MO  Stage IVB Any T, N3, M0    Any T, N3, M0  T4b, Any N, M0  Stage IVC Any T, Any N, M1 Stage IVC Any T, Any N, M1 |                                                                                                       |
appendix iv management of dental
staging-primary tumor (t)

Dental Care for Irradiated Patients Goals for a dental care program include:
1. To reduce incidence of bone necrosis. 2. To reduce incidence of irradiation caries.  
3. To allow proper fitting of dentures following treatment.
Pre-irradiation Care and Procedures The patients may be grouped into four groups in accordance with the problems they present prior to irradiation.  
Group 1 Includes edentulous patients. They may require surgical removal of any symptomatic cysts, infected retained root tips, or alveolar hyperplasia. These patients require hygiene instruction and precautionary instruction about trauma with premature use of a prosthesis.
appendix iv management of dental
group 2

Includes those with poor dental hygiene, including those patients whose teeth are beyond repair by ordinary dental procedure, those with generalized oral sepsis, those with generalized periodontal disease, and those with chronic periapical abscesses or granulomas. Procedures performed on this group include removal of all remaining teeth prior to irradiation with primary closure and surgical preparation of the alveolar ridges to laterally support a prosthesis. There should be antibiotic coverage during the healing stage and adequate time prior to the start of radiation therapy. These patients need complete hygiene instruction and precautionary instruction about premature use of a prosthesis.
appendix iv management of dental
group 3

Includes those in whom dental condition is fair, including those patients whose teeth are restored, ordinary dental procedures, periodontal pockets are less than 3 mm deep, carious lesions are not in proximity to the pulp, and no more than 20 restorable carious lesions are present. X-ray examinations show at least 1/2 of the bone still present around root surfaces. These patients require removal of any teeth that are non-salvageable in accordance with the above and restorations of the remaining teeth as required. The patients are instructed for dental prophylaxis and the patients utilize custom-made fluoride carriers.
appendix iv management of dental
group 4

Includes those in whom dental hygiene is good. This includes patients who do not have severe malocclusion in whom few carious lesions are present. Carious lesions are not in close proximity to the pulp and are correctable by conventional methods. These patients require periodontal evaluation and dental prophylaxis training, restorations as needed, no extractions prior to radiation therapy, and fitting for custom carriers.
appendix iv management of dental
extraction of teeth

If extraction of teeth is necessary prior to radiation therapy, the bone must be contoured so that closure at the extraction site is possible. All loose spicules and sharp projections must be removed. The approximation of the gingival tissue must be such that the closure is neither too loose nor too tight. At least 10 days are required for adequate healing prior to initiation of therapy.
appendix iv management of dental
causative factors

The major causative factors appear to be the reduction of the amount of saliva and secondarily, reduced pH in the mouth. This occurs following high dose radiation to the major salivary glands using parallel opposed fields. The decay process usually occurs in the first year following radiation therapy. It tends to occur more quickly in teeth which have a large amount of root cementum exposed to those teeth with large amounts of plaque formation present. Doses of radiation in excess of 20 Gy to salivary tissue place the teeth at risk.
appendix iv management of dental
appendix iv (continued) preventive program

The rationale behind the use of fluoride treatments is to make the tooth surfaces less susceptible to the decay process. This is accomplished by a combination of increasing fluoride concentration on the tooth surface and by the effect of fluoride on the plaque and flora that are present in the oral cavity. Adequate results are obtained by: 1) cleansing the teeth thoroughly, followed by a good home care dental prophylaxis program, 2) construction of fluoride carriers, custom-made mouth guards, which provide local application of fluoride solution to the gingiva and tooth surfaces. Fluoride carriers are made individually with the use of casts. Material used for making a mouth guard is "Sta-Guard" plastic used in conjunction with vacutrole unit produced by Jelrus Technical Products, Corp., both of which are available through local dental supply. This material is molded to the cast impression and allowed to harden. A fluoride solution prepared at the M.D. Anderson Hospital is now available from the Emerson Laboratories, Inc., Dallas, Texas 75221. It has been used to coat the plastic carrier for use in the mouth. The patients are instructed to cleanse their teeth prior to placement of the carrier. It is then worn in place for 5 minutes each day. The patients are instructed to rinse their mouths thoroughly following the use of the carrier. This will be continued for an indefinite period of time. Close follow-up is necessary.
appendix iv management of dental
results

In the 5-1/2 year program at the M.D. Anderson Hospital beginning in 1966, a study of 304 patients shows that the incidence of necrosis of the jaw was reduced to approximately 21% compared to 37% prior to initiation of the study. Groups 3 and 4 patients randomized with and without fluoride treatment showed reduction in radiation carries from 67% to 34% among Group 3 patients, and from 65% to 22% among Group 4 patients.
appendix iv management of dental
failure to control decay

Management of failure to control radiation decay includes silver fillings with continued use of fluoride treatments. If the decay process is sufficiently advanced that a filling will no longer stay in place, these teeth are merely smoothed so that there will be no sharp, irritating edges. The mere existence of such a decayed tooth is not necessarily reason for extraction, for it must be remembered that extraction could lead to complications such as bone necrosis. Pulp exposure resulting from the decay process can usually be handled by use of antibiotics and/or root-canal therapy. Hypersensitivity of Teeth Occasionally, a patient will exhibit extreme sensitivity of the teeth secondary to diminished amounts of saliva. This has been shown to be reduced in incidence with the fluoride treatments. Should this problem become manifest, increasing the fluoride treatment to 10 to 15 minutes 3 times a day is recommended.
appendix iv management of dental
infections

Infections occurring in patients under or after radiation therapy are best managed conservatively with good oral hygiene, irrigation and flushing procedures, and systemic antibiotics.
appendix iv management of dental
bone necrosis

The patients receiving radiation therapy to a high dose to the head and neck region have increased susceptibility to bone necrosis for several reasons including: impairment of normal metabolism, increased susceptibility to infection and severely limited repair process. Bone necrosis occurs most often after dental or oral surgery in patients who have been previously radiated. Conservative management should be tried first, though in more aggressive lesions a more radical approach may ultimately be necessary.
appendix v instructions for rtog
shipping instructions

US Postal Service Mailing Address: For Non-urgent or Non-frozen Specimens Only NRG Oncology Biospecimen Bank University of California San Francisco Campus Box 1800 2340 Sutter Street, Room S341 San Francisco, CA 94143-1800 Courier Address (FedEx, UPS, etc.): For Urgent FFPE and Frozen Specimens NRG Oncology Biospecimen Bank University of California San Francisco 2340 Sutter Street, Room S341 San Francisco, CA 94115 Include all NRG Oncology paperwork in pocket of biohazard bag. Check that the ST Form has the consent boxes checked off. Check that all samples are labeled with NRG Oncology study and case number, and include date of collection as well as collection time point.
appendix v instructions for rtog
ffpe specimens

o Slides should be shipped in a plastic slide holder/ slide box. Place a small wad of padding in top of container If you can hear the slides shaking they are likely to be break during shipping.  
o FFPE Blocks can be wrapped with paper towel, or placed in a cardboard box with padding. Do not wrap blocks with bubble wrap. Place padding in top of container so that if you shake the container the blocks are not shaking. If you hear them shaking they are likely to be breaking during shipping.  
o Slides, Blocks or Plugs can be shipped ambient or with a cold pack either by USPS to the USPS
address (94143) or by Courier to the Street Address (94115). Do NOT ship on Dry Ice.
appendix v instructions for rtog
frozen specimens

o Multiple cases may be shipped in the same cooler, but make sure each one is in a separate bag and clearly identified.  
o Place specimens and absorbent shipping material in Styrofoam cooler filled with dry ice (at least 7 lbs).  
There should be plenty of dry ice under and above the specimens. If the volume of specimens is greater than the volume of dry ice then ship in a larger Styrofoam box, or two separate boxes. Any Styrofoam box can be used, as long as it is big enough.  
o Specimens received thawed due to insufficient dry ice or shipping delays will be discarded and the site will be notified.  
o Send frozen specimens via overnight courier to the address above. Specimens should only be shipped Monday through Wednesday (Monday-Tuesday for Canada) to prevent thawing due to delivery delays. Saturday or holiday deliveries cannot be accepted. Samples can be stored frozen at -80C until ready to ship.  
**For questions regarding collection/shipping, please contact the NRG Oncology Biospecimen Bank**
by e-mail at: RTOG@ucsf.edu; or (415)-476-7864; or fax (415)-476-5271
Continued on next page NRG Oncology FFPE SPECIMEN PLUG KIT INSTRUCTIONS
This Kit allows sub-sampling of an FFPE block for submission to the NRG Oncology Biospecimen Bank.  
 The plug kit contains a shipping tube and a punch tool.  
Step 1 If the block is stored cold, allow it to equilibrate for 30 minutes at room temperature. Place the punch tool on the paraffin block over the selected tumor area. (Ask a pathologist to select area with tumor.) Push the punch into the paraffin block. Twist the punch tool once around to separate the plug from the block. Then pull the punch tool out of the block. The punch should be filled with tissue sample.  
Step 2 Label the punch tool with the proper specimen ID. DON'T remove specimen from the punch.  
Use a separate punch tool for every specimen. Call or e-mail us if you have any questions or need additional specimen plug kits. Step 3 Once punch tool is labeled, place in shipping tube and mail to address below. Please do not mix specimens in the same tube.  
We will remove core specimen from the punch, embed in a paraffin block, and label with specimen ID. *NOTE: If your facility is uncomfortable obtaining the plug but wants to retain the tissue block, please send the entire block to the NRG Oncology Biospecimen Bank and we will sample a plug from the block and return the remaining block to your facility. Please indicate on the submission form the request to perform the plug procedure and return of the block. Ship specimen plug kit, specimen in punch tool, and all paperwork to the address below. For Questions regarding collection/shipping or to order an FFPE Specimen Plug Kit, please contact the NRG Oncology Biospecimen Bank by e-mail: RTOG@ucsf.edu or call 415-476-7864/Fax 415-476-5271.  
U.S. Postal Service Mailing Address: For Non-urgent and Non-frozen Specimens Only NRG Oncology Biospecimen Bank University of California San Francisco Campus Box 1800 2340 Sutter Street, Room S341 San Francisco, CA 94143-1800 Courier Address (FedEx, UPS, etc.): For Urgent FFPE and Frozen Specimens shipments NRG Oncology Biospecimen Bank University of California San Francisco 2340 Sutter Street, Room S341 San Francisco, CA 94115
nrg oncology blood collection kit
this kit is for collection

One Red Top tube for serum (A)
One Purple Top EDTA tube for plasma (B)
One Purple Top EDTA tube for Whole Blood (C)
Twenty five (25) 1 ml cryovials Styrofoam container (inner)
Cardboard shipping (outer) box Kit Instructions Specimen Transmittal (ST) Form Absorbent shipping material (3)
Biohazard bags (3)
UN1845 DRY Ice Sticker UN3373 Biological Substance Category B
Stickers
nrg oncology blood collection kit
preparation and processing of serum

Label as many 1ml cryovials (5 to 10) as necessary for the serum collected. Label them with the NRG
Oncology study and case number, collection date, time, and time point, and clearly mark cryovials
"serum".  
Process: 1. Allow one red top tube to clot for 30 minutes at room temperature.  
2. Spin in a standard clinical centrifuge at ~2500 RPM for 10 minutes at 4C (preferred). If sites are unable to process samples at 4C then spinning at room temperature is acceptable if done within 2 hours of draw but must be noted on the ST Form.  
3. Aliquot 0.5 ml serum into as many cryovials as are necessary for the serum collected (5 to 10) labeled with NRG Oncology study and case numbers, collection date/time, protocol time-point collected (e.g. pretreatment, 3 or 6 month follow up post-treatment), and clearly mark specimen as "serum".  
4. Place cryovials into biohazard bag and immediately freeze at -70 to -90 C, and store frozen until ready to ship. See below for storage conditions.  
5. Store serum at -70 to -90 C until ready to ship on dry ice. See below for storage conditions.
nrg oncology blood collection kit
please make sure that every

Label as many 1ml cryovials (5 to 10) as necessary for the plasma collected. Label them with the NRG Oncology study and case number, collection date, time, and time point, and clearly mark cryovials "plasma".
nrg oncology blood collection kit
process

1. After collection, invert tube(s) multiple times to ensure adequate mixing of EDTA. 2. Centrifuge specimen(s) within one hour of collection in a standard clinical centrifuge at ~2500 RPM for 10 minutes at 4C (preferred). If sites are unable to process samples at 4C then spinning at room temperature is acceptable if done within 2 hours of draw but must be noted on the ST Form.  
3. If the interval between specimen collection and processing is anticipated to be more than one hour, keep specimen on ice until centrifuging is performed. 4. Carefully pipette and aliquot 0.5 ml plasma into as many cryovials as are necessary for the plasma collected ( 5to 10) labeled with NRG Oncology study and case numbers, collection date/time, time point collected and clearly mark specimen as "plasma". Avoid pipetting up the buffy coat layer.  
5. Place cryovials into biohazard bag and immediately freeze at -70 to -90C
6. Store frozen plasma at -70 to -90° C until ready to ship on dry ice. 7. See below for storage conditions.
nrg oncology blood collection kit
please make sure that every

C) **Whole Blood For DNA:Purple Top EDTA tube \#2**
Label as many 1ml cryovials (3 to 5) as necessary for the whole blood collected. Label them with the NRG Oncology study and case number, collection date, time, and time point, and clearly mark cryovial(s) "blood".  
Process:
1. After collection, invert tube(s) multiple times to ensure adequate mixing of EDTA. Blood can also be mixed for 5 minutes on a mixer at room temperature.  
2. Carefully pipette and aliquot 1.0 ml blood into as many cryovials as are necessary for the blood collected (3 to 5) labeled with NRG Oncology study and case numbers, collection date/time, time point collected and clearly mark specimen as "blood".  
3. Place cryovials into biohazard bag and freeze immediately at -70 to -80 Celsius. 4. Store blood samples frozen -70 to -90° C until ready to ship on dry ice.  
5. See below for storage conditions.
nrg oncology blood collection kit
please make sure that every

Freeze Blood samples in a -80C Freezer or on Dry Ice or snap freeze in liquid nitrogen.  
Store at –80C (-70C to -90C) until ready to ship.  
If a -80C Freezer is not available, Samples can be stored short term in a -20 C Freezer (non-frost free preferred) for up to one week (please ship out Monday-Wednesday only- Canada Mon-Tues).  
OR: Samples can be stored in plenty of Dry Ice for up to one week, replenishing daily (please ship out on Monday-Wednesday only- Canada Mon-Tues).  
OR: Samples can be stored in liq. nitrogen vapor phase (ship out Monday-Wednesday only- Canada Mon-Tues).  
Please indicate on Specimen Transmittal (ST) Form the storage conditions used and time stored.  
Shipping/Mailing:
Ship specimens on Dry Ice overnight Monday-Wednesday **(Monday-Tuesday from Canada)** to prevent thawing due to delivery delays. Saturday and holiday deliveries cannot be accepted.  
Specimens received thawed due to insufficient dry ice or shipping delays will be discarded and the site will be notified.  
Include all NRG Oncology paperwork in a sealed plastic and tape to the outside top of the Styrofoam box.  
Wrap frozen specimens of same type (i.e., all serum together, plasma together and whole bloods together) in absorbent shipping material and place each specimen type in a separate biohazard bag. Place specimen bags into the Styrofoam cooler and fill with plenty of dry ice (7-10 lbs/3.5kg minimum). Add padding to avoid the dry ice breaking the tubes.  
Place Styrofoam coolers into outer cardboard box, and attach shipping label and UN3373 and UN1895 stickers to outer cardboard box.  
Multiple cases may be shipped in the same cooler, but make sure each one is in a separate bag and that there is enough room for plenty of dry ice.  
For questions regarding collection, shipping or to order a Blood Collection Kit, please e-mail RTOG@ucsf.edu or call (415) 476-7864 or fax (415) 476-5271
nrg oncology blood collection kit
shipping address

Courier Address (FedEx, UPS, etc.): For all Frozen Specimens NRG Oncology Biospecimen Bank at UCSF
2340 Sutter Street, Room S341 San Francisco, CA 94115 For questions, call: 415-476- (7864) or e-mail: RTOG@ucsf.edu
nrg oncology blood collection kit
appendix vi dental tooth count

Use the diagram below as a guide to count the number of native teeth in place, not including full or partial dentures or bridges.  
The exact location of teeth does not need to be recorded, only the total number of native teeth in place (attached to bone in mandible or maxilla) on the day of evaluation.  
This exam should be completed by a physician or designee, such as a physician's assistant, nurse or nurse practitioner, or a dentist/hygienist. Date of evaluation: Total number of native teeth in place (0-32):  
  
0 Normal: Edentulous, with no gingival disease; native teeth in place with gingiva in excellent condition.  
1 Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; < 5 restorations indicated; no extractions indicated.  
2 Moderate/fair dental health: moderate periodontal inflammation; deep periodontal cleaning indicated; 6 or more restorations indicated; less than full mouth extractions indicated.  
3 Severe changes in dental health: widespread periodontal disease with extensive procedure/surgery indicated; full mouth extractions indicated.  
4 Life-threatening dental condition: extensive abscess, extensive soft issue or bone infection, sepsis; urgent intervention indicated.