Glottic Carcinoma
Conditions
Brief summary
This is a prospective study to determine the local control and quality-of-life outcomes of using SBRT for early-stage glottic larynx cancer.
Detailed description
SBRT treatment will be delivered to patients diagnosed with stage I-II glottic larynx cancer twice per week for 5 fractions (42.5 Gy cohort, low-risk) or daily for 16 fractions (58.08 Gy cohort, moderate-risk). Low-risk is defined by: * Planning target volume (PTV) less than 10 cc, AND * No reported smoking within 1 month from registration Moderate-risk is defined by: * Planning target volume (PTV) greater than or equal to 10 cc, OR * Smoking within 1 month from registration (no more than 1 pack per day)
Interventions
RADIATIONRadiation therapy
Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiation therapy (SBRT)
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 120 Years
Healthy volunteers
No
Inclusion criteria
1. Pathologically-proven diagnosis of squamous cell carcinoma in situ, squamous cell carcinoma or squamous cell variants (sarcomatoid, verrucous, basaloid, and papillary subtypes) involving the glottic larynx. 2. Clinical stage I-II (American Joint Committee on Cancer AJCC, 7th edition) with direct laryngoscopy showing no evidence of greater than stage II true glottic larynx cancer and PET/CT or CT neck showing no evidence of regional disease. 3. Age ≥ 18 years. 4. ECOG Performance Status 0-2 5. 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. 5.1 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). 6. Negative serum or urine pregnancy test within 2 weeks before registration for women of childbearing potential. 7. Ability to understand and the willingness to sign a written informed consent. 8. Patients with cognitive impairment or other limited decision making capacity with the ability to understand and willingly sign written informed consent or have the consent signed by a designated legally authorized representative (LAR)
Exclusion criteria
1. AJCC stage III or stage IV larynx cancer 2. Involvement of the arytenoid cartilage beyond the vocal process. 3. Prior chemotherapy for treatment of the targeted larynx lesion 4. Synchronous primaries in the head and neck 5. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields. 6. Subjects smoking in excess of 1 pack of cigarettes per day. 7. Subjects may not be receiving any other investigational agents. 8. 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. 9. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Local Failure Following SABR Treatment of Early Glottic Larynx Cancers | 2 years | Local failure is defined as biopsy-proven tumor anywhere on the true vocal cords. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Grade 3-5 Acute and Late Toxicities Following Treatment With SABR | 90 days, 3 years | Number of patients with grade 3-5 acute (start of treatment through 90 days from the completion of treatment) and late (after 90 days from the completion of treatment) adverse events, according to NCI's Common Terminology Criteria for Adverse Events (CTCAE) v4.0 toxicity criteria. |
| Health-related Quality of Life Following Treatment With SABR. | From baseline to 2 years post-treatment | Average patient visual analogue scale score (derived from EQ-5D) at baseline, 6, 12, and 24 months from the end of treatment The Visual Analogue Score (VAS) of the EQ-5D is a visual scale from 0-100, with 100 being perfect health, where patients can mark their perceived health. Researchers can then take the average score across all patients for each timepoint. |
| Percentage of Participants With Locoregional Failure Following SABR With Death as a Competing Risk | 2 years | Specifically, the 2-year cumulative risk of biopsy-proven recurrence anywhere in the larynx or neck following SABR. Recurrence in this context includes biopsy-proven cancer anywhere in the supraglottic, glottic, or subglottic larynx, as well as any malignant lymph node in the cervical or supraclavicular lymph nodes. |
| Voice-quality Score Following Treatment With SABR | From baseline to 2 years post-treatment | Voice Handicap Index (VHI) voice-quality score to monitor changes in self-perception of voice handicap before and after treatment. 0-30 Mild Minimal amount of handicap 31-60 Moderate handicap 60-120 Severe handicap |
| Percentage of Patient Population With Regional Failure and Distant Metastasis | 2 years | With death and prior locoregional failure as competing risks |
| Laryngectomy-free Survival | 2 years | Laryngectomy-free survival probability at 2 years |
| Overall Survival | 2 years | Overall survival |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients Receiving SBRT All patients on the clinical trial are receiving SBRT. Early-stage larynx cancer patients; all patients received SBRT (study treatment) at one of two different dose levels based on cohort (determined by whether the patient was low or moderate risk). The treatment fields are identical in both cohorts, and are expected to have the same patterns-of-failure. The dosing of these patients is not experimental and therefore was not a factor in analysis: all patients were analyzed together, as all received the same experimental treatment (SBRT). The biologically effective dose of this regimen is identical according to EQD2 (equivalent dose in 2 Gray fractions) analysis; in 5 fractions, the dose was equivalent to 65.52 Gy, and in 16 fractions, the dose was equivalent to 65.28 Gy. Therefore the biological impact of both regimens was the same, and this equivalence is why we analyzed the AE's together. The only potential difference between these dosing regimens is in late effects (1 year and after), but we saw no grade 2 or higher adverse events in either cohort, eliminating the need to report out late adverse events separately. | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Patients Receiving SBRT |
|---|---|
| Age, Customized Age of patients | 72 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 2 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 24 Participants |
| Smoking Active | 1 participants |
| Smoking None | 8 participants |
| Smoking Previous | 16 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 25 |
| other Total, other adverse events | 25 / 25 |
| serious Total, serious adverse events | 2 / 25 |
Outcome results
Primary
Number of Patients With Local Failure Following SABR Treatment of Early Glottic Larynx Cancers
Local failure is defined as biopsy-proven tumor anywhere on the true vocal cords.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients | Number of Patients With Local Failure Following SABR Treatment of Early Glottic Larynx Cancers | 2 participants |
Secondary
Health-related Quality of Life Following Treatment With SABR.
Average patient visual analogue scale score (derived from EQ-5D) at baseline, 6, 12, and 24 months from the end of treatment The Visual Analogue Score (VAS) of the EQ-5D is a visual scale from 0-100, with 100 being perfect health, where patients can mark their perceived health. Researchers can then take the average score across all patients for each timepoint.
Time frame: From baseline to 2 years post-treatment
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| All Patients | Health-related Quality of Life Following Treatment With SABR. | 24 Months | 85.5 score on a scale |
| All Patients | Health-related Quality of Life Following Treatment With SABR. | Baseline | 78 score on a scale |
| All Patients | Health-related Quality of Life Following Treatment With SABR. | 6 Months | 86.2 score on a scale |
| All Patients | Health-related Quality of Life Following Treatment With SABR. | 12 Months | 83.2 score on a scale |
Secondary
Laryngectomy-free Survival
Laryngectomy-free survival probability at 2 years
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients | Laryngectomy-free Survival | 88 Percentage of patients with LFS at 2 yrs |
Secondary
Number of Patients With Grade 3-5 Acute and Late Toxicities Following Treatment With SABR
Number of patients with grade 3-5 acute (start of treatment through 90 days from the completion of treatment) and late (after 90 days from the completion of treatment) adverse events, according to NCI's Common Terminology Criteria for Adverse Events (CTCAE) v4.0 toxicity criteria.
Time frame: 90 days, 3 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients | Number of Patients With Grade 3-5 Acute and Late Toxicities Following Treatment With SABR | Acute | 6 participants |
| All Patients | Number of Patients With Grade 3-5 Acute and Late Toxicities Following Treatment With SABR | Late | 19 participants |
Secondary
Overall Survival
Overall survival
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients | Overall Survival | Passed | 4 patients |
| All Patients | Overall Survival | Survival | 21 patients |
Secondary
Percentage of Participants With Locoregional Failure Following SABR With Death as a Competing Risk
Specifically, the 2-year cumulative risk of biopsy-proven recurrence anywhere in the larynx or neck following SABR. Recurrence in this context includes biopsy-proven cancer anywhere in the supraglottic, glottic, or subglottic larynx, as well as any malignant lymph node in the cervical or supraclavicular lymph nodes.
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients | Percentage of Participants With Locoregional Failure Following SABR With Death as a Competing Risk | 2 Years | 8 Percentage of participants |
| All Patients | Percentage of Participants With Locoregional Failure Following SABR With Death as a Competing Risk | 1 Year | 4 Percentage of participants |
Secondary
Percentage of Patient Population With Regional Failure and Distant Metastasis
With death and prior locoregional failure as competing risks
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients | Percentage of Patient Population With Regional Failure and Distant Metastasis | 2-year distant metastasis | 8 Percentage of participants |
| All Patients | Percentage of Patient Population With Regional Failure and Distant Metastasis | 2-year regional recurrence | 8 Percentage of participants |
Secondary
Voice-quality Score Following Treatment With SABR
Voice Handicap Index (VHI) voice-quality score to monitor changes in self-perception of voice handicap before and after treatment. 0-30 Mild Minimal amount of handicap 31-60 Moderate handicap 60-120 Severe handicap
Time frame: From baseline to 2 years post-treatment
Population: Participants who were able and willing to fill out PROs
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Patients | Voice-quality Score Following Treatment With SABR | 28.5 score on a scale |
| 6M Follow up | Voice-quality Score Following Treatment With SABR | 4 score on a scale |
| 12M Follow up | Voice-quality Score Following Treatment With SABR | 7.5 score on a scale |
| 24M Follow Up | Voice-quality Score Following Treatment With SABR | 7.5 score on a scale |
| Baseline | Voice-quality Score Following Treatment With SABR | 57 score on a scale |