Head and Neck Squamous Cell Carcinoma
Conditions
Brief summary
Elective nodal irradiation has been a longstanding standard-of-care in the management of mucosal squamous cell carcinoma of the head and neck. Recent studies have suggested that reduced elective dose and volume may be a viable approach to improve toxicity. In this study, we are eliminating the elective neck treatment, focusing therapy on involved and suspicious nodes.
Detailed description
We recently completed and reported a successful study (INFIELD) using reduced elective dose (40 Gy) and volume (involved echelons + 1) for oropharynx and larynx cancer. In INRT-AIR (Involved Nodal Radiotherapy using AI-based Radiomics), we are eliminating the elective neck treatment altogether, using radiologic and radiomic-based criteria to focus treatment on the nodes themselves. Eligible patients include previously untreated patients with stage I-IVB oropharynx, larynx and hypopharynx cancer, excluding T1-2 glottic carcinoma. Patients requiring chemotherapy may receive cisplatin, cetuximab, or carboplatin-paclitexel.
Interventions
RADIATIONIntensity modulated radiation therapy (IMRT)
Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel). 6.5-7 weeks of radiotherapy or chemoradiotherapy
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Pathologically-proven diagnosis of squamous cell carcinoma of the oropharynx, larynx, or hypopharynx. Squamous cell carcinoma of unknown primary is not allowed. 2. Patients must have clinically or radiographically evident measureable disease at the primary site and/or nodal stations. Diagnostic lymph node excision (\< 2 nodes) is also allowable. 3. Patients may undergo a diagnostic or therapeutic transoral resection for a T1-2 tonsil or base of tongue cancer. 4. Clinical stage I-IVB (AJCC, 7th edition); stages I-II glottic cancer are excluded 5. Age ≥ 18 years. 6. ECOG Performance Status 0-2 7. 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. 7.1 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). 8. Negative serum pregnancy test within 2 weeks before registration for women of childbearing potential. 9. Neck CT and/or neck MRI, and PET-CT (at least skull-to-thigh). 10. Ability to understand and the willingness to sign a written informed consent.
Exclusion criteria
1. Distant metastasis. 2. Inability to undergo PET-CT. 3. Stage I and II glottic carcinoma. 4. Gross total excision of both the primary and nodal disease. 5. Synchronous non-skin cancer primaries outside of the oropharynx, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous well-differentiated thyroid cancer; in the latter case, surgery may occur before or after treatment, provided all other eligibility criteria are met . 6. Prior invasive malignancy with an expected disease-free interval of less than 3 years. 7. Prior systemic chemotherapy for the study cancer; prior chemotherapy for a remote cancer is allowable 8. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields. 9. Subjects may not be receiving any other investigational agents. 10. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy agents in this study (if necessary). 11. 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, in the opinion of the investigator, would limit compliance with study requirements 12. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. 13. History of severe immunosuppression, including HIV, and organ or autologous or allogeneic stem cell transplant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Risk of Solitary Elective Volume Recurrence Following Elective Volume Reduction Using INRT | 2 years | Definition: solitary means that the recurrence occurred without a preceding or synchronous in-field or distant recurrence By definition, local recurrence (LR) means disease recurrence in the primary site, and regional recurrence (RR) is a nodal failure anywhere in the neck. Patients who experienced either an LR or RR (or both), were also coded as a locoregional recurrence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of SEVR Risks by Anatomic Site | 2 years | OS= Overall survival PFS= Progression-free survival |
| European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Summary Score and Functional Subscales | Baseline, 3 months, 6 months, 12 months, 24 months | The EORTC QLQ-C30 is a 30-item instrument (30 questions). Results are calculated from the means of the scores from the summary score and the functional QLQ-C30 scales. Higher scores indicate better quality of life, on a scale from 0 to 100. Patients answer questions that are grouped into the following scales: Summary score (scored from 0-100, with higher scores indicating a better quality of life) -Global (Patients rate overall health and quality of life) Functional scales (each of these is scored from 0-100, with higher scores indicating a better quality of life) * Physical function (ability to perform physical tasks) * Role function (ability to perform daily and work-related activities) * Emotional function (whether patient is experiencing distress, anxiety, depression) * Cognitive function (memory, concentration) * Social function (ability to maintain social activities and relationships) |
| European Organization for Research and Treatment of Cancer Head and Neck 35-question Questionnaire (EORTC HN35) Symptom Subscales | Baseline, 3 month, 6 month, 12 month, 24 months | Patients report to which extent they experience symptoms or problems during one week. EORTC HN35 subscales are each scored on a scale from 0 to 100, with higher scores indicating worse symptoms. These subscales include dry mouth, sticky saliva, senses (taste/smell), pain, and speech issues |
| MD Anderson Dysphagia Inventory (MDADI) Global, Emotional, Functional and Physical Subscales | Baseline, 3 months, 6 months, 12 months, 24 months | Questionnaire asks for patients' views about swallowing ability. MDADI scores range from 20 to 100, where higher scores represent better swallowing ability. |
| Skin Toxicity (Dermatitis) | 2 years | According to National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v4.0 toxicity criteria Higher grades indicate worse adverse events. This is assessed clinically by the patient's physician. Grade 1 is defined as "Faint erythema or dry desquamation" Grade 2 is defined as "Moderate to brisk erythema; patchy moist desquamation, mostly confined to skin folds and creases; moderate edema" Grade 3 is defined as "Moist Desquamation in areas other than skin folds and creases; bleeding induced by minor trauma or abrasion" |
| Gastrostomy Placement | from end of treatment to 2 years post treatment | Number of patients who experienced gastrostomy dependence for a period of time following treatment with INRT up to 2 years post treatment |
| EQ-5D Quality of Life Overall Health Visual Analogue Scale (VAS) | Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months from the end of treatment | Average patient utilities (derived from EQ-5D) at baseline, 1, 3, 6, 12, 18, 24 and 36 months from the end of treatment. The overall health VAS is scored from 0 (worst imaginable health) to 100 (best imaginable health) based on the patient's self-reported health that day. |
| 2-year Overall and Progression-free Survival Following Treatment With INRT | 2 years | Overall survival (PFS) is defined as the duration of time from start of treatment to time of progression (LR, RR, or DM) or death. Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression (LR, RR, or DM) or death. |
| Time From the End of Treatment for Disease-free Patients to Have Their Gastrostomy Tubes Removed | 2 years | Median length of gastrostomy dependence following treatment with INRT for patients who had needed a gastrostomy tube inserted and who were deemed disease-free |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDavid J Sher, MD, MPH
University of Texas Southwestern Medical Center
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62 years |
| Disease Site Larynx/hypopharynx | 19 Participants |
| Disease Site p16- oropharynx | 5 Participants |
| Disease Site p16+ Oropharynx | 43 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 66 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 61 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 67 |
| other Total, other adverse events | 67 / 67 |
| serious Total, serious adverse events | 12 / 67 |
Outcome results
None listed