De-intensification of Radiation & Chemotherapy in Low-Risk Human Papillomavirus-related Oropharyngeal Squamous Cell Ca

• ClinicalTrials.gov Identifier: NCT01530997
• Recruitment Status: Active, not recruiting
• First Posted: February 10, 2012
• Results First Posted: August 9, 2017
• Last Update Posted: March 9, 2020
• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Information provided by (Responsible Party): UNC Lineberger Comprehensive Cancer Center

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Oropharyngeal Neoplasms
• Interventions: Radiation: Intensity Modulated Radiotherapy (IMRT); Drug: Cisplatin; Procedure: Limited surgical evaluation
• Enrollment: 45

Participant Flow

Recruitment Details	Enrolling institutions included University of North Carolina Hospitals (Chapel Hill, NC), University of Florida Hospitals (Gainesville, FL), and Rex Hospital (Raleigh, NC).
Pre-assignment Details	Sixty-nine patients were eligible for enrollment, of whom 45 were accrued. One patient had a cerebrovascular accident during de-intensified CRT and was taken off the study. After the completion of CRT, 1 patient refused the planned surgical evaluation, leaving 43 patients who were fully evaluable.

Arm/Group Title	Single Intervention
Arm/Group Description	Patients received 60 Gy of Intensity Modulated Radiotherapy (IMRT) with concurrent weekly intravenous cisplatin (30 mg/m2). Diagnostic imaging (CT and/or MRI) was obtained 4 to 8 weeks after completion of CRT to assess response. Patients received surgical resection of any clinically apparent residual primary tumor or biopsy of the primary site if there was no evidence of residual tumor and underwent a limited neck dissection to encompass at least those nodal level(s) that were positive pre-treatment, 4 to 14 weeks after CRT. Intensity Modulated Radiotherapy (IMRT): All patients received IMRT. Dose painting IMRT was used and all doses were specified to the planning target volume (PTV). The high risk planning target volume (PTV-HR) and standard risk planning target volume (PTV-SR) was treated to the following respective total doses: 60 Gy and 54 Gy. The dose per fraction to the PTV-HR and PTV-SR was 2 Gy/day and 1.8 Gy/day, respectively.
Period Title: Overall Study
Started	45
Completed	43
Not Completed	2
Reason Not Completed
Physician Decision	1
Withdrawal by Subject	1

Baseline Characteristics

Arm/Group Title		De-escalated Radiation and Chemotherapy
Arm/Group Description		Patients received 60 Gy of Intensity Modulated Radiotherapy (IMRT) with concurrent weekly intravenous cisplatin (30 mg/m2). Diagnostic imaging (CT and/or MRI) was obtained 4 to 8 weeks after completion of CRT to assess response. Patients received surgical resection of any clinically apparent residual primary tumor or biopsy of the primary site if there was no evidence of residual tumor and underwent a limited neck dissection to encompass at least those nodal level(s) that were positive pre-treatment, 4 to 14 weeks after CRT. Intensity Modulated Radiotherapy (IMRT): All patients received IMRT. Dose painting IMRT was used and all doses were specified to the planning target volume (PTV). The high risk planning target volume (PTV-HR) and standard risk planning target volume (PTV-SR) was treated to the following respective total doses: 60 Gy and 54 Gy. The dose per fraction to the PTV-HR and PTV-SR was 2 Gy/day and 1.8 Gy/day, respectively.
Overall Number of Baseline Participants		44
Baseline Analysis Population Description		Sixty-nine patients were eligible for enrollment, of whom 45 were accrued. One patient had a cerebrovascular accident during de-intensified CRT and was taken off the study leaving 44 patients included in the baseline characteristics.
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	44 participants
		61; (44 to 76)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	44 participants
	Female	39 88.6%
	Male	5 11.4%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	44 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	4 9.1%
	White	40 90.9%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	44 participants
		44
Marital Status; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	44 participants
	Married	34 77.3%
	Unmarried	10 22.7%
Tobacco Use; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	44 participants
	Never Smoker	36 81.8%
	<=10 Pack Years	6 13.6%
	> 10 Pack Years	2 4.5%
Primary Tumor Location; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	44 participants
	Tonsil	16 36.4%
	Base of Tongue	26 59.1%
	Unknown Primary	2 4.5%
T Stage [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	44 participants
	T0	2 4.5%
	T1	13 29.5%
	T2	22 50.0%
	T3	7 15.9%
		[1] Measure Description: The Classification of Malignant Tumours (TNM) system is the most widely used cancer staging system. The T refers to the size and extent of the main tumor. N refers to the regional lymph nodes. N0 means there is no cancer in nearby lymph nodes. The larger the number following N means the more lymph nodes that contain cancer.
N Stage [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	44 participants
	N0	4 9.1%
	N1	10 22.7%
	N2a	2 4.5%
	N2b	21 47.7%
	N2c	7 15.9%
		[1] Measure Description: The Classification of Malignant Tumours (TNM) system is the most widely used cancer staging system. The T refers to the size and extent of the main tumor. N refers to the regional lymph nodes. N0 means there is no cancer in nearby lymph nodes. The larger the number following N means the more lymph nodes that contain cancer.
HPV/p16 Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	44 participants
	HPV+/p16+	28 63.6%
	HPV-/p16+	16 36.4%
		[1] Measure Description: Human papilloma virus (HPV) is a common virus that can cause cancer. p16 is a tumor suppression gene that acts as a cyclin-dependent kinase inhibitor. HPV-related cancers with p16 overexpression (p16+) have a better prognosis than those not related to HPV due to an increased sensitivity to radiotherapy.

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response Rate After De-escalated CRT in HPV-positive and/or p16 Positive Oropharyngeal Squamous Cell Carcinoma (OPSCC).
Description	Pathologic Complete Response Rate is defined as no evidence of residual viable cancer in the evaluated pathological specimens.
Time Frame	6 to 14 weeks after the last patient is enrolled, or approximately 24 to 32 months after study being opened

Outcome Measure Data

Analysis Population Description

Following the completion of chemoradiation therapy (CRT), 1 patient refused the planned surgical evaluation and 43 patients were evaluated.

Arm/Group Title	De-escalated Radiation and Chemotherapy
Arm/Group Description:	Patients received 60 Gy of Intensity Modulated Radiotherapy (IMRT) with concurrent weekly intravenous cisplatin (30 mg/m2). Diagnostic imaging (CT and/or MRI) was obtained 4 to 8 weeks after completion of CRT to assess response. Patients received surgical resection of any clinically apparent residual primary tumor or biopsy of the primary site if there was no evidence of residual tumor and underwent a limited neck dissection to encompass at least those nodal level(s) that were positive pre-treatment, 4 to 14 weeks after CRT. Intensity Modulated Radiotherapy (IMRT): All patients received IMRT. Dose painting IMRT was used and all doses were specified to the planning target volume (PTV). The high risk planning target volume (PTV-HR) and standard risk planning target volume (PTV-SR) was treated to the following respective total doses: 60 Gy and 54 Gy. The dose per fraction to the PTV-HR and PTV-SR was 2 Gy/day and 1.8 Gy/day, respectively.
Overall Number of Participants Analyzed	43
Measure Type: Count of Participants; Unit of Measure: Participants
	37 86.0%

2. Secondary Outcome

Title	Two-Year Local Control
Description	Local control is the arrest of cancer growth at the site of origin.
Time Frame	Median follow-up was 36 months with a range of 5-53 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	De-escalated Radiation and Chemotherapy
Arm/Group Description:	Patients received 60 Gy of Intensity Modulated Radiotherapy (IMRT) with concurrent weekly intravenous cisplatin (30 mg/m2). Diagnostic imaging (CT and/or MRI) was obtained 4 to 8 weeks after completion of CRT to assess response. Patients received surgical resection of any clinically apparent residual primary tumor or biopsy of the primary site if there was no evidence of residual tumor and underwent a limited neck dissection to encompass at least those nodal level(s) that were positive pre-treatment, 4 to 14 weeks after CRT. Intensity Modulated Radiotherapy (IMRT): All patients received IMRT. Dose painting IMRT was used and all doses were specified to the planning target volume (PTV). The high risk planning target volume (PTV-HR) and standard risk planning target volume (PTV-SR) was treated to the following respective total doses: 60 Gy and 54 Gy. The dose per fraction to the PTV-HR and PTV-SR was 2 Gy/day and 1.8 Gy/day, respectively.
Overall Number of Participants Analyzed	44
Measure Type: Number; Unit of Measure: percentage of participants
	100

3. Secondary Outcome

Title	Regional Control
Description	Regional control is the percentage of participants who displayed control of cancer in sites that represent the first stages of spread from the local origin.
Time Frame	Median follow-up was 36 months with a range of 5-53 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Intervention
Arm/Group Description:	Patients received 60 Gy of Intensity Modulated Radiotherapy (IMRT) with concurrent weekly intravenous cisplatin (30 mg/m2). Diagnostic imaging (CT and/or MRI) was obtained 4 to 8 weeks after completion of CRT to assess response. Patients received surgical resection of any clinically apparent residual primary tumor or biopsy of the primary site if there was no evidence of residual tumor and underwent a limited neck dissection to encompass at least those nodal level(s) that were positive pre-treatment, 4 to 14 weeks after CRT. Intensity Modulated Radiotherapy (IMRT): All patients received IMRT. Dose painting IMRT was used and all doses were specified to the planning target volume (PTV). The high risk planning target volume (PTV-HR) and standard risk planning target volume (PTV-SR) was treated to the following respective total doses: 60 Gy and 54 Gy. The dose per fraction to the PTV-HR and PTV-SR was 2 Gy/day and 1.8 Gy/day, respectively.
Overall Number of Participants Analyzed	44
Measure Type: Number; Unit of Measure: percentage of participants
	100

4. Secondary Outcome

Title	Cause-Specific Survival
Description	Cause-specific survival is the percentage of participants who have not died from low-risk low-risk OPSCC.
Time Frame	The median follow-up was 36 months with a range of 5-53 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Intervention
Arm/Group Description:	Patients received 60 Gy of Intensity Modulated Radiotherapy (IMRT) with concurrent weekly intravenous cisplatin (30 mg/m2). Diagnostic imaging (CT and/or MRI) was obtained 4 to 8 weeks after completion of CRT to assess response. Patients received surgical resection of any clinically apparent residual primary tumor or biopsy of the primary site if there was no evidence of residual tumor and underwent a limited neck dissection to encompass at least those nodal level(s) that were positive pre-treatment, 4 to 14 weeks after CRT. Intensity Modulated Radiotherapy (IMRT): All patients received IMRT. Dose painting IMRT was used and all doses were specified to the planning target volume (PTV). The high risk planning target volume (PTV-HR) and standard risk planning target volume (PTV-SR) was treated to the following respective total doses: 60 Gy and 54 Gy. The dose per fraction to the PTV-HR and PTV-SR was 2 Gy/day and 1.8 Gy/day, respectively.
Overall Number of Participants Analyzed	44
Measure Type: Number; Unit of Measure: percentage of participants
	100

5. Secondary Outcome

Title	Distant Metastases Free Survival
Description	Distant metastases free survival is the percentage of subjects in a study who have survived without cancer spread.
Time Frame	the median follow-up was 36 months with a range of

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Intervention
Arm/Group Description:	Patients received 60 Gy of Intensity Modulated Radiotherapy (IMRT) with concurrent weekly intravenous cisplatin (30 mg/m2). Diagnostic imaging (CT and/or MRI) was obtained 4 to 8 weeks after completion of CRT to assess response. Patients received surgical resection of any clinically apparent residual primary tumor or biopsy of the primary site if there was no evidence of residual tumor and underwent a limited neck dissection to encompass at least those nodal level(s) that were positive pre-treatment, 4 to 14 weeks after CRT. Intensity Modulated Radiotherapy (IMRT): All patients received IMRT. Dose painting IMRT was used and all doses were specified to the planning target volume (PTV). The high risk planning target volume (PTV-HR) and standard risk planning target volume (PTV-SR) was treated to the following respective total doses: 60 Gy and 54 Gy. The dose per fraction to the PTV-HR and PTV-SR was 2 Gy/day and 1.8 Gy/day, respectively.
Overall Number of Participants Analyzed	44
Measure Type: Number; Unit of Measure: percentage of participants
	100

6. Secondary Outcome

Title	Overall Survival Rate
Description	The percentage of participants who are still alive from the start of treatment.
Time Frame	Median follow-up was 36 months with a range of 5-53 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Intervention
Arm/Group Description:	Patients received 60 Gy of Intensity Modulated Radiotherapy (IMRT) with concurrent weekly intravenous cisplatin (30 mg/m2). Diagnostic imaging (CT and/or MRI) was obtained 4 to 8 weeks after completion of CRT to assess response. Patients received surgical resection of any clinically apparent residual primary tumor or biopsy of the primary site if there was no evidence of residual tumor and underwent a limited neck dissection to encompass at least those nodal level(s) that were positive pre-treatment, 4 to 14 weeks after CRT. Intensity Modulated Radiotherapy (IMRT): All patients received IMRT. Dose painting IMRT was used and all doses were specified to the planning target volume (PTV). The high risk planning target volume (PTV-HR) and standard risk planning target volume (PTV-SR) was treated to the following respective total doses: 60 Gy and 54 Gy. The dose per fraction to the PTV-HR and PTV-SR was 2 Gy/day and 1.8 Gy/day, respectively.
Overall Number of Participants Analyzed	44
Measure Type: Number; Unit of Measure: percentage of participants
	95

7. Secondary Outcome

Title	European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-H&N-35
Description	The head & neck cancer module of the EORTC QLQ comprises 35 questions assessing symptoms and side effects of treatment, social function and body image/sexuality. The head & neck cancer module incorporates seven multi-item scales that assess pain, swallowing, senses (taste and smell), speech, social eating, social contact and sexuality. There are also eleven single items. Most questions used 4 point scale (1 'Not at all' to 4 'Very much'); several single item questions (Pain killers, nutritional supplements, feeding tube, weight loss, and weight gain) were just coded as no=1, yes=2. The scores of these scales were averaged from the scores of the component items, transformed and analyzed on a 0 - 100 scale. For all items and scales, high scores indicate more problems (i.e. there are no function scales in which high scores would mean better functioning).
Time Frame	Prior to CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline	6-8 Weeks Post-Treatment	Post-Surgery
Arm/Group Description:	This data was collected pre-chemoradiotherapy treatment.	This data was collected 6-8 weeks post-chemoradiotherapy.	This data was collected at the first follow-up post-surgery.
Overall Number of Participants Analyzed	44	42	42
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Pain	19; (14 to 25)	25; (18 to 32)	26; (20 to 33)
Swallowing	11; (7 to 14)	19; (13 to 25)	18; (13 to 24)
Senses Problems	5; (2 to 8)	35; (29 to 40)	28; (22 to 34)
Speech Problems	10; (5 to 15)	13; (8 to 18)	16; (11 to 22)
Trouble with Social Eating	8; (5 to 11)	29; (22 to 37)	24; (18 to 31)
Trouble with Social Contact	5; (2 to 8)	15; (9 to 20)	8; (4 to 12)
Less Sexuality	13; (7 to 19)	34; (24 to 45)	23; (15 to 31)
Teeth	3; (0 to 6)	10; (5 to 16)	12; (6 to 18)
Opening Mouth	5; (1 to 8)	15; (9 to 21)	18; (12 to 25)
Dry Mouth	16; (10 to 22)	69; (61 to 77)	64; (56 to 72)
Sticky Saliva	6; (2 to 10)	61; (51 to 72)	49; (41 to 58)
Cough	17; (11 to 24)	25; (17 to 34)	22; (15 to 29)
Felt Ill	8; (3 to 12)	20; (11 to 28)	11; (5 to 17)
Pain Killers	34; (20 to 48)	43; (28 to 58)	33; (19 to 48)
Nutritional Supplements	39; (24 to 53)	55; (40 to 70)	40; (25 to 56)
Feeding Tube	0; (0 to 0)	40; (25 to 56)	17; (5 to 28)
Weight Loss	20; (8 to 33)	38; (23 to 53)	36; (21 to 50)
Weight Gain	25; (12 to 38)	40; (25 to 56)	10; (1 to 19)

8. Secondary Outcome

Title	European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status/QoL
Description	The EORTC QLQ-C30 is a cancer-specific instrument with 30 questions which incorporates 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social); 9 symptom scales (fatigue, pain, nausea and vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties); and a global health and quality-of-life scale. Most questions used 4 point scale (1 'Not at all' to 4 'Very much'); 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). The scores of these scales were averaged from the scores of the component items, transformed and analyzed on a 0 - 100 scale. A higher score=better level of functioning or greater degree of symptoms.
Time Frame	Prior to CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline	6-8 Weeks Post-Treatment	Post-Surgery
Arm/Group Description:	This data was collected pre-chemoradiotherapy treatment.	This data was collected 6-8 weeks post-chemoradiotherapy.	This data was collected at the first follow-up post-surgery.
Overall Number of Participants Analyzed	44	42	42
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Global health status/QoL	80; (75 to 85)	61; (55 to 68)	69; (64 to 75)
Physical functioning	96; (93 to 98)	78; (72 to 84)	85; (79 to 90)
Role functioning	96; (93 to 98)	65; (57 to 74)	77; (69 to 84)
Emotional functioning	77; (70 to 84)	77; (70 to 84)	84; (78 to 90)
Cognitive functioning	91; (87 to 95)	86; (81 to 92)	87; (82 to 92)
Social functioning	88; (83 to 93)	66; (58 to 74)	81; (75 to 87)
Fatigue	20; (14 to 25)	42; (34 to 50)	31; (26 to 37)
Nausea and vomiting	2; (0 to 3)	13; (8 to 17)	4; (1 to 6)
Pain	15; (10 to 21)	21; (13 to 29)	20; (13 to 27)
Dyspnea	5; (1 to 8)	11; (5 to 17)	6; (1 to 10)
Insomnia	23; (16 to 30)	34; (25 to 43)	23; (15 to 31)
Appetite loss	14; (8 to 19)	40; (30 to 49)	33; (24 to 42)
Constipation	12; (5 to 18)	17; (10 to 23)	16; (9 to 23)
Diarrhea	5; (1 to 8)	4; (1 to 7)	6; (2 to 10)
Financial difficulties	16; (8 to 24)	28; (17 to 39)	22; (14 to 30)

9. Secondary Outcome

Title	The Eating Assessment Tool (EAT-10) Composite Score
Description	The EAT-10 is a 10 item, validated self-administered instrument for documenting dysphagia severity. This questionnaire uses symptom-specific scores to assess dysphasia with solids, liquids, and pills as well as the impact of dysphagia on mental, social, and physical health. Higher raw scores represent worse QoL. All items have a 0-4 scale where 0 represents no problem and 4 represents severe problem. Total score can range from 0 to 40.
Time Frame	Prior to CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline	6-8 Weeks Post-Treatment	Post-Surgery
Arm/Group Description:	This data was collected pre-chemoradiotherapy treatment.	This data was collected 6-8 weeks post-chemoradiotherapy.	This data was collected at the first follow-up post surgery.
Overall Number of Participants Analyzed	43	41	42
Mean (95% Confidence Interval); Unit of Measure: units on a scale
	4; (2 to 5)	13; (9 to 16)	11; (8 to 14)

10. Secondary Outcome

Title	The Rosenbek Penetration Aspiration Scale
Description	The Rosenbek Penetration Aspiration Scale will be used to quantify dysphagia. It is an 8-point, equal-appearing interval scale to describe penetration and aspiration events. The measure was used for thin substances, pureed substances, and solid substances. 1. Material does not enter airway 2. Material enters the airway, remains above the vocal folds, and is ejected from the airway. 3. Material enters the airway, remains above the vocal folds, and is not ejected from the airway. 4. Material enters the airway, contacts the vocal folds, and is ejected from the airway. 5. Material enters the airway, contacts the vocal folds, and is not ejected from the airway. 6.Material enters the airway, passes below the vocal folds, and is ejected into the larynx or out of the airway. 7. Material enters the airway, passes below the vocal folds, and is not ejected from the trachea despite effort. 8. Material enters the airway, passes below the vocal folds, and no effort is made to eject.
Time Frame	Prior to CRT and 4-8 weeks after completion of CRT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pre-treatment	Post-treatment
Arm/Group Description:	This data was collected before the treatment.	This data was collected 4-8 weeks after chemoradiation therapy
Overall Number of Participants Analyzed	37	31
Mean (Standard Deviation); Unit of Measure: units on a scale
Thin Substances	1.30 (.62)	1.90 (1.83)
Pureed Substances	1.03 (0.16)	1.19 (0.54)
Solid Substances	1.03 (0.16)	1.03 (0.19)

Adverse Events

Time Frame	4 years
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Single Intervention
Arm/Group Description	Patients received 60 Gy of Intensity Modulated Radiotherapy (IMRT) with concurrent weekly intravenous cisplatin (30 mg/m2). Diagnostic imaging (CT and/or MRI) was obtained 4 to 8 weeks after completion of CRT to assess response. Patients received surgical resection of any clinically apparent residual primary tumor or biopsy of the primary site if there was no evidence of residual tumor and underwent a limited neck dissection to encompass at least those nodal level(s) that were positive pre-treatment, 4 to 14 weeks after CRT. Intensity Modulated Radiotherapy (IMRT): All patients received IMRT. Dose painting IMRT was used and all doses were specified to the planning target volume (PTV). The high risk planning target volume (PTV-HR) and standard risk planning target volume (PTV-SR) was treated to the following respective total doses: 60 Gy and 54 Gy. The dose per fraction to the PTV-HR and PTV-SR was 2 Gy/day and 1.8 Gy/day, respectively
All-Cause Mortality
	Single Intervention
	Affected / at Risk (%)
Total	1/45 (2.22%)
Serious Adverse Events
	Single Intervention
	Affected / at Risk (%)
Total	15/45 (33.33%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, specify * 1 [1]	1/45 (2.22%)
Blood and lymphatic system disorders - Other, specify * 1 [2]	1/45 (2.22%)
Febrile neutropenia * 1	1/45 (2.22%)
Gastrointestinal disorders
Constipation * 1	1/45 (2.22%)
Diarrhea * 1	1/45 (2.22%)
Nausea * 1	1/45 (2.22%)
Vomiting * 1	2/45 (4.44%)
General disorders
Fever * 1	1/45 (2.22%)
Infections and infestations
Sepsis * 1	1/45 (2.22%)
Urinary tract infection * 1	1/45 (2.22%)
Soft tissue infection * 1	1/45 (2.22%)
Investigations
Alanine aminotransferase increased * 1	1/45 (2.22%)
Aspartate aminotransferase increased * 1	1/45 (2.22%)
Metabolism and nutrition disorders
Dehydration * 1	2/45 (4.44%)
Hyponatremia * 1	1/45 (2.22%)
Anorexia * 1	1/45 (2.22%)
Nervous system disorders
Stroke * 1	1/45 (2.22%)
Respiratory, thoracic and mediastinal disorders
Aspiration * 1	2/45 (4.44%)
Vascular disorders
Hematoma * 1	1/45 (2.22%)
Hypotension * 1	1/45 (2.22%)
1 Term from vocabulary, CTCAE (4.0); * Indicates events were collected by non-systematic assessment; [1] Pulmonary embolus/Blood clot; [2] Bleeding
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Single Intervention
	Affected / at Risk (%)
Total	40/45 (88.89%)
Blood and lymphatic system disorders
Anemia * 1	3/45 (6.67%)
Ear and labyrinth disorders
Middle ear inflammation * 1	1/45 (2.22%)
Tinnitus * 1	16/45 (35.56%)
Endocrine disorders
Hypothyroidism * 1	2/45 (4.44%)
Gastrointestinal disorders
Abdominal pain * 1	1/45 (2.22%)
Constipation * 1	2/45 (4.44%)
Dry mouth * 1	32/45 (71.11%)
Dysphagia * 1	32/45 (71.11%)
Esophageal pain * 1	1/45 (2.22%)
Esophageal stenosis * 1	1/45 (2.22%)
Mucositis oral * 1	34/45 (75.56%)
Nausea * 1	28/45 (62.22%)
Vomiting * 1	18/45 (40.00%)
Diarrea * 1	1/45 (2.22%)
General disorders
Fatigue * 1	32/45 (71.11%)
Fever * 1	1/45 (2.22%)
Infusion site extravasation * 1	1/45 (2.22%)
Neck edema * 1	29/45 (64.44%)
Pain * 1	34/45 (75.56%)
Immune system disorders
Allergic reaction * 1	1/45 (2.22%)
Infections and infestations
Mucosal infection * 1	1/45 (2.22%)
Salivary gland infection * 1	1/45 (2.22%)
Sinusitis * 1	1/45 (2.22%)
Soft tissue infection * 1	2/45 (4.44%)
Upper respiratory infection * 1	1/45 (2.22%)
Infections and infestations - Other, specify * 1 [1]	1/45 (2.22%)
Injury, poisoning and procedural complications
Dermatitis radiation * 1	32/45 (71.11%)
Investigations
Alanine aminotransferase increased * 1	1/45 (2.22%)
Neutrophil count decreased * 1	1/45 (2.22%)
Platelet count decreased * 1	2/45 (4.44%)
Weight loss * 1	4/45 (8.89%)
White blood cell decreased * 1	1/45 (2.22%)
Lymphopenia * 1	1/45 (2.22%)
Metabolism and nutrition disorders
Anorexia * 1	31/45 (68.89%)
Dehydration * 1	5/45 (11.11%)
Hyperglycemia * 1	1/45 (2.22%)
Hypoalbuminemia * 1	1/45 (2.22%)
Hyponatremia * 1	3/45 (6.67%)
Musculoskeletal and connective tissue disorders
Osteonecrosis of jaw * 1	2/45 (4.44%)
Trismus * 1	1/45 (2.22%)
Nervous system disorders
Dysgeusia * 1	32/45 (71.11%)
Syncope * 1	2/45 (4.44%)
Vagus nerve disorder * 1	1/45 (2.22%)
Psychiatric disorders
Anxiety * 1	19/45 (42.22%)
Depression * 1	14/45 (31.11%)
Renal and urinary disorders
Acute kidney injury * 1	3/45 (6.67%)
Respiratory, thoracic and mediastinal disorders
Hoarseness * 1	7/45 (15.56%)
Nasal congestion * 1	1/45 (2.22%)
Pharyngeal mucositis * 1	31/45 (68.89%)
Voice alteration * 1	11/45 (24.44%)
Respiratory, thoracic and mediastinal disorders - Other, specify * 1 [2]	1/45 (2.22%)
Skin and subcutaneous tissue disorders
Alopecia * 1	29/45 (64.44%)
Rash acneiform * 1	1/45 (2.22%)
Surgical and medical procedures
Surgical and medical procedures - Other, specify * 1	4/45 (8.89%)
1 Term from vocabulary, CTCAE (4.0); * Indicates events were collected by non-systematic assessment; [1] Respiratory Infection; [2] Severely altered eating/swallowing

Limitations and Caveats

Per the protocol, affiliate sites will only report grade 3/4 and all fatal (grade 5) toxicities. 1/2 toxicities were not reported for affiliate sites.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Robin V. Johnson
• Organization: UNC Lineberger Comprehensive Cancer Center
• Phone: 919-966-1125
• EMail: Robin_V_Johnson@med.unc.edu

Publications:

Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mavroidis P, Price A, Fried D, Kostich M, Amdur R, Mendenhall W, Liu C, Das S, Marks LB, Chera B. Dose-volume toxicity modeling for de-intensified chemo-radiation therapy for HPV-positive oropharynx cancer. Radiother Oncol. 2017 Aug;124(2):240-247. doi: 10.1016/j.radonc.2017.06.020. Epub 2017 Jul 13.

Chera BS, Amdur RJ, Tepper J, Qaqish B, Green R, Aumer SL, Hayes N, Weiss J, Grilley-Olson J, Zanation A, Hackman T, Funkhouser W, Sheets N, Weissler M, Mendenhall W. Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. Int J Radiat Oncol Biol Phys. 2015 Dec 1;93(5):976-85. doi: 10.1016/j.ijrobp.2015.08.033. Epub 2015 Aug 22.

• Responsible Party: UNC Lineberger Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT01530997
• Other Study ID Numbers: LCCC 1120
• First Submitted: January 20, 2012
• First Posted: February 10, 2012
• Results First Submitted: March 30, 2017
• Results First Posted: August 9, 2017
• Last Update Posted: March 9, 2020