INFIELD: Involved Field Elective Volume De-Intensification Radiation Therapy for Head and Neck Cancer

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT03067610
• Collaborator: (none)
• Enrollment: 72
• Locations: 2
• Arm: 1
• Actual Duration (Months): 49.6
• Patients Per Site: 36
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel)

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer; Carcinoma, Squamous Cell; Neoplasms, Oral; Neoplasms, Pharyngeal	Radiation: Intensity Modulated Radiation Therapy; Drug: chemotherapy	Phase 2

Detailed Description

This study aims to significantly improve the acute and late morbidity of patients with oropharyngeal and laryngeal squamous cell carcinoma both by tailoring the elective irradiation only to regions with a legitimate risk of recurrence (> 5%) and by lowering the elective dose to 40 Gy. Level IB will not be electively treated unless it is involved with pathologic or suspicious lymphadenopathy. Level V will not be treated unless two or more ipsilateral nodal levels are involved (or level V itself has pathologic or suspicious adenopathy). Levels III and IV will only be irradiated if the immediately proximal level contains pathologic lymphadenopathy (i.e. level III irradiated if level II is positive; level IV irradiated if level III is positive). We anticipate that this approach should dramatically improve the acute and late complication profile.

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: radiation therapyradiation therapy
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective Phase II Study of Involved Field Elective Volume De-Intensification for Oropharyngeal and Laryngeal Squamous Cell Carcinoma Treated With Intensity Modulated Radiation Therapy
• Actual Study Start Date: Jan 20, 2017
• Actual Primary Completion Date: Dec 21, 2020
• Actual Study Completion Date: Mar 9, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Radiation Therapy Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel)

Radiation: Intensity Modulated Radiation Therapy; The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction.; Other Names: IMRT ; Drug: chemotherapy; chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion; Other Names: cisplatin, cetuximab, or carboplatin-paclitaxel

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Solitary Elective Volume Recurrence [2 years]

   The crude risk of 2-year solitary elective volume recurrence will be calculated among all patients who are followed for at least 2 years. Patients who die before 2 years without an SEVR will be included in the denominator.

Secondary Outcome Measures

1. Quality of Life (QOL) Patient Reported Outcomes (PRO) [12 months]

   Quality of life (QOL) patient-reported outcomes (PRO) for overall number of participants following treatment with elective volume and dose de-escalation, using European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), EORTC HN35, which is specific to head and neck cancer, and composite MD Anderson Dysphagia Inventory (MDADI). EORTC QLQ-C30 and QLQ-H&N35 are scored on a 4-point categorical scale ranging from 1 "not at all" to 4 "very much". This scale is then linearly transformed to a 0-100 scale, where a higher score represents a higher response level. A high score for a functional scale represents higher level functioning, a high score for quality of life represents a high quality of life, and a high score for a symptom scale represents worse symptoms. MD Anderson Dysphagia Inventory (MDADI) questionnaire: Possible score ranges from 0-100, with higher score indicating higher functioning.

2. Number of Participants With Definite, Possible, and Probable Protocol-related Toxicities (Grade 3-5) [2 years]

   Only adverse events (grade 3-5) assessed to be definitely, probably, or possibly related to protocol treatment up to 2 years post-treatment will be considered. This was measured according to NCI's CTCAE v4.0 toxicity criteria.

3. Total Number of Participants With Gastrostomy Dependence [2 years]

   The prevalence of gastrostomy use up to 2 years will be described.

4. Patient Utilities [2 years]

   The average patient utilities (derived from EQ-5D) from baseline up to 2 years from the end of treatment will be described. Changes in patient utility will be analyzed using generalized estimated equations (GEE).

5. Overall Survival [2 years]

   Overall survival will be calculated from the initiation of treatment using the Kaplan-Meier method.

6. Progression-free Survival [2 year]

   Progression-free survival will be calculated from the initiation of treatment. Progression is confirmed by biopsy, which will be used as the date of progression.

7. Probability of Locoregional or Distant Tumor Failure [2 years]

   The percentage of patients with locoregional or distant failure within 2 years of treatment will be estimated using cumulative incidence statistics, with death serving as the competing risk. Cumulative incidence refers to the estimated risk/probability of tumor failure within 2 years of treatment, either locoregional recurrence or distant metastasis, accounting for the competing risk of death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Pathologically-proven diagnosis of squamous cell carcinoma of the oropharynx or larynx. Squamous cell carcinoma of unknown primary is not allowed.

• Patients must have clinically or radiographically evident measureable disease at the primary site and/or nodal stations. Patients may undergo a diagnostic tonsillectomy, and diagnostic lymph node excision (< 2 nodes) is also allowable.

• Clinical stage I-IVB (AJCC, 7th edition); stages I-II glottic cancer are excluded

• Age ≥ 18 years.

• ECOG Performance Status 0-2

• Adequate organ and marrow function as defined below:

• leukocytes ≥ 3,000/mcL

• absolute neutrophil count ≥ 1,500/mcL

• platelets ≥ 100,000/mcl

• total bilirubin within normal institutional limits

• AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

• A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or

• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

• Negative serum or urine pregnancy test within 2 weeks before registration for women of childbearing potential.

• Neck CT and/or neck MRI, and whole body PET-CT.

• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• Distant metastasis or adenopathy below the clavicles.

• Inability to undergo PET-CT.

• Stage I and II glottic carcinoma.

• Gross total excision of both the primary and nodal disease.

• Synchronous primaries outside of the oropharynx and larynx.

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease-free for a minimum of 1 years

• Prior systemic chemotherapy for the study cancer; prior chemotherapy for a remote cancer is allowable

• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields.

• Subjects may not be receiving any other investigational agents.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy agents in this study (if necessary).

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

• History of immunosuppression or autoimmunity, including HIV, and organ or stem cell transplant, or an autoimmune condition previously treated with immunosuppressive therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rush University Medical Center	Chicago	Illinois	United States	60612
2	University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390

Sponsors and Collaborators

• University of Texas Southwestern Medical Center

Investigators

• Principal Investigator: David Sher, MD, MPH, U Texas Southwestern Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 18, 2021

More Information

Publications

None provided.

• Responsible Party: David Sher, Professor of Medicine, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT03067610
• Other Study ID Numbers: STU 052016-044
• First Posted: Mar 1, 2017
• Last Update Posted: Mar 17, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma; Neoplasms; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Mouth Neoplasms; Pharyngeal Neoplasms; Paclitaxel; Cisplatin; Carboplatin; Cetuximab

Study Results

Participant Flow

Arm/Group Title	Radiation Therapy
Arm/Group Description	Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel). There was only one study arm. The radiation field and dose are the same with or without chemotherapy. The intent is to assess the effects of radiation therapy, regardless of chemotherapy treatment. Intensity Modulated Radiation Therapy: The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction. chemotherapy: chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion
Period Title: Overall Study
STARTED	72
COMPLETED	72
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Radiation Therapy
Arm/Group Description	Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) Intensity Modulated Radiation Therapy: The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction. chemotherapy: chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion
Overall Participants	72
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.5 (10.9)
Sex: Female, Male (Count of Participants)
Female	13 18.1%
Male	59 81.9%
Race/Ethnicity, Customized (Count of Participants)
White	58 80.6%
Black	8 11.1%
Hispanic	4 5.6%
Other	2 2.8%
Region of Enrollment (participants) [Number]
United States	72 100%
Disease site (Count of Participants)
Oropharynx	51 70.8%
Larynx	21 29.2%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Solitary Elective Volume Recurrence
Description	The crude risk of 2-year solitary elective volume recurrence will be calculated among all patients who are followed for at least 2 years. Patients who die before 2 years without an SEVR will be included in the denominator.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation Therapy
Arm/Group Description	Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) Intensity Modulated Radiation Therapy: The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction. chemotherapy: chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion
Measure Participants	72
Count of Participants [Participants]	0 0%

2. Secondary Outcome

Title	Quality of Life (QOL) Patient Reported Outcomes (PRO)
Description	Quality of life (QOL) patient-reported outcomes (PRO) for overall number of participants following treatment with elective volume and dose de-escalation, using European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), EORTC HN35, which is specific to head and neck cancer, and composite MD Anderson Dysphagia Inventory (MDADI). EORTC QLQ-C30 and QLQ-H&N35 are scored on a 4-point categorical scale ranging from 1 "not at all" to 4 "very much". This scale is then linearly transformed to a 0-100 scale, where a higher score represents a higher response level. A high score for a functional scale represents higher level functioning, a high score for quality of life represents a high quality of life, and a high score for a symptom scale represents worse symptoms. MD Anderson Dysphagia Inventory (MDADI) questionnaire: Possible score ranges from 0-100, with higher score indicating higher functioning.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Total Cohort Baseline	Total Cohort 3 Month	Total Cohort 6 Month	Total Cohort 12 Month
Arm/Group Description	Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) Intensity Modulated Radiation Therapy: The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction. chemotherapy: chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion	Total cohort	Total cohort	Total cohort
Measure Participants	72	57	44	43
EORTC QLQ30 global	71.4 (2.3)	76.9 (2.6)	79.2 (2.8)	85.9 (2.3)
EORTC QLQ30 physical fcn	90.3 (1.7)	87.4 (2.3)	90.3 (2.4)	93.0 (1.8)
EORTC QLQ30 role fcn	81.9 (3.0)	82.5 (3.4)	85.6 (3.6)	95.3 (2.2)
EORTC QLQ30 emotional fcn	78.0 (2.8)	87.7 (2.7)	82.9 (3.7)	88.2 (3.2)
EORTC QLQ30 cognitive fcn	90.0 (1.9)	89.5 (2.7)	86.4 (3.1)	90.7 (2.9)
EORTC QLQ30 social fcn	85.2 (2.4)	85.1 (3.5)	85.6 (3.7)	90.3 (3.4)
EORTC HN35 dry mouth	14.4 (2.8)	59.0 (4.1)	47.7 (4.5)	38.0 (4.2)
EORTC HN35 sticky saliva	15.7 (3.2)	38.0 (4.4)	27.3 (4.4)	27.1 (4.6)
EORTC HN35 senses	6.7 (1.8)	25.7 (2.9)	20.1 (3.3)	15.9 (2.7)
EORTC HN35 pain	24.4 (2.7)	16.5 (2.7)	14.2 (3.3)	7.9 (2.3)
EORTC HN35 speech	18.4 (2.9)	13.4 (2.6)	19.2 (4.5)	9.8 (2.6)
Composite MDADI	81.3 (1.9)	79.6 (2.0)	76.9 (2.6)	84.9 (2.3)

3. Secondary Outcome

Title	Number of Participants With Definite, Possible, and Probable Protocol-related Toxicities (Grade 3-5)
Description	Only adverse events (grade 3-5) assessed to be definitely, probably, or possibly related to protocol treatment up to 2 years post-treatment will be considered. This was measured according to NCI's CTCAE v4.0 toxicity criteria.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation Therapy
Arm/Group Description	Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) Intensity Modulated Radiation Therapy: The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction. chemotherapy: chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion
Measure Participants	33
Count of Participants [Participants]	3 4.2%

4. Secondary Outcome

Title	Total Number of Participants With Gastrostomy Dependence
Description	The prevalence of gastrostomy use up to 2 years will be described.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation Therapy
Arm/Group Description	Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) Intensity Modulated Radiation Therapy: The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction. chemotherapy: chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion
Measure Participants	72
Count of Participants [Participants]	31 43.1%

5. Secondary Outcome

Title	Patient Utilities
Description	The average patient utilities (derived from EQ-5D) from baseline up to 2 years from the end of treatment will be described. Changes in patient utility will be analyzed using generalized estimated equations (GEE).
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Collected data were not considered valid due to software limitations as it was not available to auto-calculate the data as proposed by our EMR

Arm/Group Title	Radiation Therapy
Arm/Group Description	Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) Intensity Modulated Radiation Therapy: The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction. chemotherapy: chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion
Measure Participants	0

6. Secondary Outcome

Title	Overall Survival
Description	Overall survival will be calculated from the initiation of treatment using the Kaplan-Meier method.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Reported the percentage of the total patient population who survived to 2 years post-treatment.

Arm/Group Title	Radiation Therapy
Arm/Group Description	Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) Intensity Modulated Radiation Therapy: The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction. chemotherapy: chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion
Measure Participants	72
Number [percentage of patients]	89

7. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival will be calculated from the initiation of treatment. Progression is confirmed by biopsy, which will be used as the date of progression.
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

Percentage of the total patient population with progression-free survival 2 years post treatment

Arm/Group Title	Radiation Therapy
Arm/Group Description	Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) Intensity Modulated Radiation Therapy: The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction. chemotherapy: chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion
Measure Participants	72
Number [percentage of patients]	79

8. Secondary Outcome

Title	Probability of Locoregional or Distant Tumor Failure
Description	The percentage of patients with locoregional or distant failure within 2 years of treatment will be estimated using cumulative incidence statistics, with death serving as the competing risk. Cumulative incidence refers to the estimated risk/probability of tumor failure within 2 years of treatment, either locoregional recurrence or distant metastasis, accounting for the competing risk of death.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation Therapy
Arm/Group Description	Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) Intensity Modulated Radiation Therapy: The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction. chemotherapy: chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion
Measure Participants	72
Locoregional recurrence	14
Distant metastasis	14

Adverse Events

Time Frame	30 months
Arm/Group Title	Radiation Therapy
Arm/Group Description	Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) Intensity Modulated Radiation Therapy: The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction. chemotherapy: chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion
All Cause Mortality
	Radiation Therapy
	Affected / at Risk (%)	# Events
Total	1/72 (1.4%)
Serious Adverse Events
	Radiation Therapy
	Affected / at Risk (%)	# Events
Total	35/72 (48.6%)
Blood and lymphatic system disorders
anemia	1/72 (1.4%)	1
febrile neutropenia	2/72 (2.8%)	2
Gastrointestinal disorders
Abdominal Pain	1/72 (1.4%)	1
dysphagia	14/72 (19.4%)	14
nausea	4/72 (5.6%)	4
Oral Hemorrhage	2/72 (2.8%)	2
Oral Mucositis	2/72 (2.8%)	2
General disorders
Atypical Chest Pain	1/72 (1.4%)	1
chills	1/72 (1.4%)	1
fatigue	1/72 (1.4%)	1
fever	1/72 (1.4%)	1
Neutropenic Fever	1/72 (1.4%)	1
Opioid Overdose	1/72 (1.4%)	1
Severe systemic inflammatory response syndrome	1/72 (1.4%)	1
Immune system disorders
Allergic Reaction	1/72 (1.4%)	1
Infections and infestations
Lung infection	3/72 (4.2%)	3
sepsis	2/72 (2.8%)	2
Skin infection (cellulitis )	1/72 (1.4%)	1
Injury, poisoning and procedural complications
Fracture	1/72 (1.4%)	1
Radiation Dermatitis	1/72 (1.4%)	1
Metabolism and nutrition disorders
Anorexia	7/72 (9.7%)	7
Dehydration	8/72 (11.1%)	8
hypernatremia	1/72 (1.4%)	1
hyponatremia	2/72 (2.8%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm of unknown etiology	1/72 (1.4%)	1
Nervous system disorders
Acute Encephalopathy	1/72 (1.4%)	1
dizziness	1/72 (1.4%)	1
parethesia	1/72 (1.4%)	1
seizure	1/72 (1.4%)	1
Psychiatric disorders
Delirium	1/72 (1.4%)	1
depression	1/72 (1.4%)	1
Renal and urinary disorders
Acute kidney injury	2/72 (2.8%)	3
Respiratory, thoracic and mediastinal disorders
aspiration	2/72 (2.8%)	2
Dyspnea	4/72 (5.6%)	4
Hypercapnic Respiratory Failure	1/72 (1.4%)	1
hypoxia	1/72 (1.4%)	1
Vascular disorders
acute mescenteric ischemia	1/72 (1.4%)	1
Hypertension	1/72 (1.4%)	1
hypotensive	1/72 (1.4%)	1
Other (Not Including Serious) Adverse Events
	Radiation Therapy
	Affected / at Risk (%)	# Events
Total	65/72 (90.3%)
Blood and lymphatic system disorders
anemia	45/72 (62.5%)	115
Factor V	1/72 (1.4%)	1
Neutropenia	1/72 (1.4%)	1
Cardiac disorders
Atrial Fibrillation	1/72 (1.4%)
Bradycardia	1/72 (1.4%)
Coronary Artery Disease	2/72 (2.8%)
chest wall pain	1/72 (1.4%)
Palpitations	1/72 (1.4%)	1
Sinus tachycardia	1/72 (1.4%)	1
Tachycardia	8/72 (11.1%)	10
Ear and labyrinth disorders
ear ache	1/72 (1.4%)
ear congestion	2/72 (2.8%)
Ear disorder - other	1/72 (1.4%)
Ear infection	2/72 (2.8%)
ear pain	17/72 (23.6%)
Hearing impaired	2/72 (2.8%)	2
Hearing loss	13/72 (18.1%)	14
Middle-ear infection	1/72 (1.4%)	1
Otalgia	1/72 (1.4%)	2
Otic pain (L ear)	1/72 (1.4%)	1
R Otalgia	1/72 (1.4%)	1
Right ear pain	1/72 (1.4%)	1
Tinnitus	20/72 (27.8%)	28
Endocrine disorders
Hyperthyroid	1/72 (1.4%)	1
Hypothyroidism	5/72 (6.9%)	5
Eye disorders
blurred vision	10/72 (13.9%)	11
blurred vision	11/72 (15.3%)
double vision	1/72 (1.4%)
eye disorder- other	1/72 (1.4%)	1
Eye pain	1/72 (1.4%)	1
Eye redness	1/72 (1.4%)	1
Photophobia	1/72 (1.4%)	2
Red eyes	1/72 (1.4%)	1
Right eye pain	1/72 (1.4%)	1
Gastrointestinal disorders
Abdominal distension	1/72 (1.4%)
abdominal pain	18/72 (25%)
Acid Reflex	11/72 (15.3%)
appetite change	2/72 (2.8%)
Bloating	3/72 (4.2%)
bowel incontinence	1/72 (1.4%)
Cheilitis	1/72 (1.4%)
constipation	55/72 (76.4%)
Diarrhea	24/72 (33.3%)
dry mouth	60/72 (83.3%)
Dsyphagia	1/72 (1.4%)
Dyspepsia	5/72 (6.9%)
Dysphagia	63/72 (87.5%)
esophagitis	1/72 (1.4%)
Fecal incontinence	1/72 (1.4%)	1
G tube dysfunction	3/72 (4.2%)	3
G tube placement	2/72 (2.8%)	2
Gastroesophageal reflux	1/72 (1.4%)	1
Gastrointestinal disorders - other, melena	1/72 (1.4%)	1
Gastroparesis	2/72 (2.8%)	2
GERD	2/72 (2.8%)	2
Gingival ulceration	1/72 (1.4%)	1
Heartburn	2/72 (2.8%)	2
Hematochezia (rectal bleeding)	1/72 (1.4%)	1
Hemorrhoidal hemorrhage	1/72 (1.4%)	1
Hypersalivation	2/72 (2.8%)	3
Mild odynophagia	1/72 (1.4%)	1
Mouth pain	1/72 (1.4%)	1
Mouth sores	1/72 (1.4%)	1
Mucositis	26/72 (36.1%)	47
Nausea	50/72 (69.4%)	97
Odynophagia	65/72 (90.3%)	148
Oral hemorrhage	1/72 (1.4%)	1
Oral lesions	1/72 (1.4%)	1
Oral mucositis	43/72 (59.7%)	88
Oral pain	56/72 (77.8%)	124
rectal bleeding	1/72 (1.4%)	1
rectal fissue	1/72 (1.4%)	1
Rectal pain	1/72 (1.4%)	1
Reflux	1/72 (1.4%)	1
Saliva pooling	1/72 (1.4%)	1
Salivary duct inflammation	4/72 (5.6%)	6
Salivary inflammation	1/72 (1.4%)	1
Thick saliva	7/72 (9.7%)	7
Toothache	2/72 (2.8%)	2
Vomiting	26/72 (36.1%)	46
Xerostomia	1/72 (1.4%)	1
General disorders
abscess of chin	1/72 (1.4%)
altered mental status	4/72 (5.6%)
Arm pain	1/72 (1.4%)
asthenia	1/72 (1.4%)
Atypical Chest Pain	2/72 (2.8%)
BCC Nose	1/72 (1.4%)
bite wound	1/72 (1.4%)
bleeding from mouth	1/72 (1.4%)
breast swelling	1/72 (1.4%)
chest pain	6/72 (8.3%)
chest tightness	1/72 (1.4%)
chills	5/72 (6.9%)
Cold Intolerance	8/72 (11.1%)
Discolored discharge	1/72 (1.4%)
dysphonia	5/72 (6.9%)
Edema	13/72 (18.1%)
Edema limbs	1/72 (1.4%)
elbow pain	1/72 (1.4%)
Facial edema	1/72 (1.4%)	2
Facial swelling	2/72 (2.8%)	2
Fatigue	58/72 (80.6%)	103
Fever	12/72 (16.7%)	17
Foot pain	1/72 (1.4%)	1
Generalized weakness	17/72 (23.6%)	22
Heat intolerance	1/72 (1.4%)	1
Hip pain	2/72 (2.8%)	2
Inflammation	1/72 (1.4%)	1
Itching	3/72 (4.2%)	3
Jaw Pain	6/72 (8.3%)	7
LE edema	4/72 (5.6%)	4
Leukoplakia	2/72 (2.8%)	2
Localized edema	23/72 (31.9%)	30
Loss of smell	8/72 (11.1%)	9
Low total protein	1/72 (1.4%)	1
Lower extremity pain	1/72 (1.4%)	1
Lump on abdomen	1/72 (1.4%)	1
Lymphadenopathy	2/72 (2.8%)	2
Lymphadema	30/72 (41.7%)	32
Migraines	1/72 (1.4%)	1
Neck edema	6/72 (8.3%)	8
Nocturnal "sweats"	1/72 (1.4%)	1
Non-cardiac chest pain	1/72 (1.4%)	1
Nose bleeds	1/72 (1.4%)	1
Oropharyngeal edema	1/72 (1.4%)	1
Pain	7/72 (9.7%)	9
Polydipsia	6/72 (8.3%)	7
Right chin pain	1/72 (1.4%)	1
Right jaw pain	1/72 (1.4%)	1
Seasonal allergies	8/72 (11.1%)	8
Sensory change	6/72 (8.3%)	7
Speech change	2/72 (2.8%)	2
Stomal pain	4/72 (5.6%)	6
Thick secretions	49/72 (68.1%)	83
Hepatobiliary disorders
breast pain	1/72 (1.4%)
emesis	2/72 (2.8%)
Immune system disorders
Allergic Reaction	1/72 (1.4%)	1
Infections and infestations
Anaerobic infection	1/72 (1.4%)
Cellulitis	2/72 (2.8%)
dental infection	1/72 (1.4%)
Infection	7/72 (9.7%)	7
Infections and infestations - other, COVID-19	1/72 (1.4%)	1
Influenza (flu-like symptoms)	1/72 (1.4%)	1
Laryngitis	1/72 (1.4%)	1
Mucosal infection	1/72 (1.4%)	1
Oral thrush	2/72 (2.8%)	2
Papulopustular rash	1/72 (1.4%)	2
Sinusitis	2/72 (2.8%)	2
Skin infection	2/72 (2.8%)	2
Stoma site infection	1/72 (1.4%)	1
Thrush	37/72 (51.4%)	50
Tracheitis	1/72 (1.4%)	4
Urinary tract infection	5/72 (6.9%)	6
Injury, poisoning and procedural complications
Aortic injury	1/72 (1.4%)
Fall	11/72 (15.3%)	13
Fracture	3/72 (4.2%)	3
Hernia	2/72 (2.8%)	2
Infusion related reaction	1/72 (1.4%)	1
Injury, other, (mild fall injury)	1/72 (1.4%)	1
Lung infection	5/72 (6.9%)	5
Overdose	1/72 (1.4%)	1
Radiation ulceration	1/72 (1.4%)	1
Right inguinal hernia	1/72 (1.4%)	1
Ulceration	5/72 (6.9%)	6
Wound complication	1/72 (1.4%)	1
Investigations
alkaline phosphate decreased	3/72 (4.2%)	3
alkaline phosphatase increased	2/72 (2.8%)	2
ALP increased	2/72 (2.8%)
ALT decreased	3/72 (4.2%)
ALT increased	11/72 (15.3%)
AST increased	7/72 (9.7%)	9
Azotemia	1/72 (1.4%)
calcium count increased	1/72 (1.4%)
Cardiac troponin I increased	1/72 (1.4%)
creatinine decreased	7/72 (9.7%)
creatinine increased	15/72 (20.8%)
Decreased platelet count	2/72 (2.8%)
decreased WBC	2/72 (2.8%)
elevated ANC	1/72 (1.4%)
elevated bilirubin	2/72 (2.8%)
elevated CO2	1/72 (1.4%)
elevated creatinine	10/72 (13.9%)
Elevated prothrombin	1/72 (1.4%)
elevated WBC	1/72 (1.4%)
High cholesterol	3/72 (4.2%)	3
Hypochloride	23/72 (31.9%)	52
Hyperchloride	1/72 (1.4%)	1
Hypochloremia	3/72 (4.2%)	4
Hypophosphorous	2/72 (2.8%)	4
Leukocytosis	5/72 (6.9%)	6
Leukopenia	1/72 (1.4%)	2
Lymphocyte count decreased	51/72 (70.8%)	194
Neutrophil count decreased	16/72 (22.2%)	30
Neutrophil count increased	7/72 (9.7%)	13
Platelet count decreased	31/72 (43.1%)	54
Platelet count increased	2/72 (2.8%)	2
TSH elevated	1/72 (1.4%)	1
Weight gain	6/72 (8.3%)	6
Weight loss	61/72 (84.7%)	119
White blood cell count increased	8/72 (11.1%)	12
White blood cell count decreased	36/72 (50%)	93
Metabolism and nutrition disorders
Albumin Decreased	1/72 (1.4%)	1
Anorexia	25/72 (34.7%)	30
decreased appetite	3/72 (4.2%)
Dehydration	27/72 (37.5%)
Diabetes	3/72 (4.2%)
diaphoresis	9/72 (12.5%)
Hypercalcemia	8/72 (11.1%)	10
Hyperglycemia	22/72 (30.6%)	43
Hyperkalemia	12/72 (16.7%)	18
Hyperlipidemia	1/72 (1.4%)	1
Hypernatremia	3/72 (4.2%)	5
Hyperphosphatemia	1/72 (1.4%)	2
Hypoalbuminemia	13/72 (18.1%)	27
Hypocalcemia	10/72 (13.9%)	22
Hypoglycemia	4/72 (5.6%)	4
Hypokalemia	17/72 (23.6%)	32
Hypomagnesemia	15/72 (20.8%)	24
Hyponatremia	26/72 (36.1%)	54
Hypophosphatemia	4/72 (5.6%)	4
L Elbow Pain	1/72 (1.4%)	1
Obesity	1/72 (1.4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/72 (2.8%)
Arthritis	2/72 (2.8%)
back pain	15/72 (20.8%)
cervical stenosis of spine	1/72 (1.4%)
cervicalgia	1/72 (1.4%)
Fibromyalgia	1/72 (1.4%)	1
Flank Pain	1/72 (1.4%)	1
Jaw Spasm	1/72 (1.4%)	1
Joint pain	11/72 (15.3%)	12
Knee pain	2/72 (2.8%)	2
L knee pain	1/72 (1.4%)	2
Muscle spasm	1/72 (1.4%)	1
Musculoskeletal disorder - other	1/72 (1.4%)	1
Myalgias	11/72 (15.3%)	13
Neck pain	39/72 (54.2%)	58
Pain in extremity	2/72 (2.8%)	2
Rib pain	1/72 (1.4%)	1
Right arm pain	1/72 (1.4%)	1
Scoliosis	1/72 (1.4%)	1
Shoulder pain	9/72 (12.5%)	10
Trismus	7/72 (9.7%)	7
Weakness	4/72 (5.6%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign - other	2/72 (2.8%)	2
Tumor pain	1/72 (1.4%)	1
Nervous system disorders
altered sensation	2/72 (2.8%)
aphonia	1/72 (1.4%)
dizziness	21/72 (29.2%)
Dysesthesia	1/72 (1.4%)
dysgeusia	65/72 (90.3%)
Focal weakness	2/72 (2.8%)	2
Headache	18/72 (25%)	27
Lumbar stenosis	1/72 (1.4%)	1
Memory loss	1/72 (1.4%)	1
Nervous system disorder - other	1/72 (1.4%)	1
Neuropathy	3/72 (4.2%)	3
Oral dysesthesia	1/72 (1.4%)	1
Parathesia	5/72 (6.9%)	6
Peripheral neuropathy	1/72 (1.4%)	1
Peripheral sensory neuropathy	2/72 (2.8%)	2
Syncope	3/72 (4.2%)	3
Syncopal	1/72 (1.4%)	1
Tremors	3/72 (4.2%)	3
Psychiatric disorders
agitated	1/72 (1.4%)	1
anxiety	20/72 (27.8%)	23
confusion	4/72 (5.6%)
depression	15/72 (20.8%)
Hallucinations	1/72 (1.4%)	1
Insomnia	29/72 (40.3%)	32
Mental confusion	1/72 (1.4%)	1
Renal and urinary disorders
bladder incontinence	1/72 (1.4%)
Chronic Kidney Disease	3/72 (4.2%)
cystitis	1/72 (1.4%)
decreased urine output	1/72 (1.4%)
dysuria	4/72 (5.6%)
Hematuria	2/72 (2.8%)	2
Nocturia	7/72 (9.7%)	7
Bladder prolapse	1/72 (1.4%)	1
Urinary frequency	12/72 (16.7%)	12
Urinary incontinence	1/72 (1.4%)	1
Urinary retention	1/72 (1.4%)	1
Urinary urgency	7/72 (9.7%)	7
Urine output decreased	1/72 (1.4%)	1
Reproductive system and breast disorders
Sexual dysfunction	1/72 (1.4%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	6/72 (8.3%)	6
aspiration	7/72 (9.7%)	8
asthma	1/72 (1.4%)
Bronchitis	1/72 (1.4%)
Chest congestion	1/72 (1.4%)
congestion	4/72 (5.6%)
cough	24/72 (33.3%)
dry cough	1/72 (1.4%)
dypsnea	2/72 (2.8%)
dyspnea	4/72 (5.6%)
Epistaxis	2/72 (2.8%)
Hemoptysis	4/72 (5.6%)	4
Hiccups	2/72 (2.8%)	2
Hoarseness	21/72 (29.2%)	25
Hypoxia	1/72 (1.4%)	1
Laryngeal Inflammation	1/72 (1.4%)	1
Laryngeal Edema	8/72 (11.1%)	10
Mediastinal fistula	1/72 (1.4%)	1
Nasal congestion	22/72 (30.6%)	25
Orthopnea	5/72 (6.9%)	5
Pneumonitis	1/72 (1.4%)	1
Productive cough	31/72 (43.1%)	42
Respiratory disorder- other	1/72 (1.4%)	1
Respiratory failure	1/72 (1.4%)	1
Rhonchus	1/72 (1.4%)	1
Shortness of breath	3/72 (4.2%)	3
Sinus pressure	1/72 (1.4%)	1
Sleep apnea	3/72 (4.2%)	3
Snoring	11/72 (15.3%)	11
Sore throat	52/72 (72.2%)	127
Stridor	2/72 (2.8%)	4
Tachypnea	1/72 (1.4%)	1
Throat pain	12/72 (16.7%)	15
Upper respiratory infection	2/72 (2.8%)	2
Velopharyngeal insufficiency (VPI)	1/72 (1.4%)	1
Voice alteration	14/72 (19.4%)	15
wheezing	8/72 (11.1%)	8
Skin and subcutaneous tissue disorders
acne vulgaris	1/72 (1.4%)	1
Acneform rash	1/72 (1.4%)	1
alopecia	1/72 (1.4%)
change in mole	2/72 (2.8%)
contact dermatitis	1/72 (1.4%)
dermatitis	1/72 (1.4%)
discoloration of tongue	1/72 (1.4%)
Dry Skin	3/72 (4.2%)
erythema	21/72 (29.2%)
Facial rash	4/72 (5.6%)	4
Hair loss	8/72 (11.1%)	9
Hyperpigmentation	7/72 (9.7%)	7
Macular rash	1/72 (1.4%)	1
Night sweats	4/72 (5.6%)	4
Pain of skin	2/72 (2.8%)	2
Pallor	1/72 (1.4%)	1
Pruritus	3/72 (4.2%)	3
Radiation dermatitis	64/72 (88.9%)	114
Rash	14/72 (19.4%)	19
Rash acneiform	2/72 (2.8%)	2
Rash maculo-papular	1/72 (1.4%)	1
Skin lesion	1/72 (1.4%)	1
Skin disorder- other	3/72 (4.2%)	3
Skin erythema	2/72 (2.8%)	2
Skin hyperpigmentation	5/72 (6.9%)	6
Skin pigmentation	1/72 (1.4%)	1
Skin rash	1/72 (1.4%)	1
Skin ulceration	1/72 (1.4%)	1
Telangiectasia	2/72 (2.8%)	2
Surgical and medical procedures
Surgical Procedure - other	10/72 (13.9%)	10
Vascular disorders
AV block 1st Degree	1/72 (1.4%)
bloody secretion	2/72 (2.8%)
DVT	1/72 (1.4%)
easy bruising	2/72 (2.8%)
Flushing	1/72 (1.4%)	1
Hot flashes	4/72 (5.6%)	5
Hypertension	42/72 (58.3%)	88
Hypotension	12/72 (16.7%)	13
Phlebitis	1/72 (1.4%)	1
Pulmonary embolism	1/72 (1.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.