Glottic Carcinoma
Conditions
Brief summary
This non-inferiority trial will compare conventional long-course accelerated fractionation radiation therapy (AF-RT) with volumetric adaptive stereotactic body radiation therapy (SBRT) in patients with early-stage (cT1-2N0M0) glottic squamous cell carcinoma. Participants will be randomized in a 1:2 ratio to receive either AF-RT (Arm A) or adaptive SBRT (Arm B). The primary objective is to determine whether adaptive SBRT provides non-inferior local control compared with AF-RT in patients with early-stage glottic squamous cell carcinoma. Secondary analyses will evaluate treatment-related toxicity and other clinical outcomes. The study hypothesizes that adaptive SBRT will achieve local control rates that are non-inferior to those of AF-RT while offering a substantially shorter treatment course. Imaging biomarkers, transcriptome/methylome profiles, plasma biomarkers, and cfDNA will be analyzed to identify novel biomarkers that predict oncologic outcomes and treatment-related toxicity.
Interventions
RADIATIONLong course accelerated fractionation radiation therapy
RT will be administered as 6 fractions per week (single fraction per day with one day of the week has 2 fractions, 6 hours apart), 5 days per week, based on the following prescription: PTV\_6600 (high dose target for cT1 tumor): will receive 66 Gy over 33 fractions in 5.5 weeks PTV\_7000 (high dose target for cT2 tumor): will receive 70 Gy over 35 fractions in 6 weeks PTV\_5600 (elective dose target): will receive 56 Gy over 33-35 fractions in 5.5-6 weeks
RT will be administered as 2 fractions per week, with at least 2 days between consecutive fractions (e.g., Monday/Thursday), over 2 weeks, as follows: PTV\_4000 (high dose target for cT1 tumor): will receive 40 Gy over 5 fractions in 2 weeks PTV\_4250 (high dose target for cT2 tumor): will receive 42.5 Gy over 5 fractions in 2 weeks PTV\_2500 (elective dose target): will receive 25 Gy over 5 fractions in 2 weeks
Sponsors
University Health Network, Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically proven diagnosis of glottic SCC. * Patients are planned to receive definitive RT * Stage cT1-2 N0 M0 (UICC/AJCC TNM 8th Edition). * Must be ≥ 18 years of age. * Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. * Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate. Consent to provision of samples for correlative studies is optional. * Women of childbearing potential must use an accepted and effective method of contraception and/or abstain from sexual intercourse while on protocol treatment and for at least 3 months after the last day of RT. Sexually active males must use an accepted and effective method of contraception and/or abstain from sexual intercourse while on protocol treatment and for at least 3 months after RT. * Women must not be pregnant or breast-feeding. All females of childbearing potential must have a serum or urine pregnancy test to rule out pregnancy within 4 weeks prior to registration. All breastfeeding women should discontinue breastfeeding prior to study registration. * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
Exclusion criteria
* Stage III-IV larynx cancer * Patients with synchronous primary head and neck cancer outside of the larynx * Prior chemotherapy for treatment of the targeted larynx lesion * Prior RT to the head and neck region that would result in significant overlap of RT volume for the current study. * Patients who are deemed to require concurrent chemotherapy for treatment of the targeted larynx lesion * Involvement of the arytenoid cartilage beyond the vocal process * No macroscopic residual disease following diagnostic biopsy or excision (i.e., no identifiable GTV for target delineation) * Planning target volume ≥10 cc, defined as the SBRT-arm PTV (Section 6.3.8) contoured on the pre-randomization simulation scan * Reported smoking within 14 days from registration to the study. * Individuals with severe, active co-morbidity including any of the following: Chronic obstructive pulmonary disease or other pulmonary illness requiring hospitalization within 30 days of study registration, Unstable angina and/or congestive heart failure requiring hospitalization within the 30 days of study registration, Acute myocardial infarction within 30 days of study registration, Diseases precluding RT (e.g., active scleroderma or lupus) * Participants must not be receiving any other standard anti-cancer therapy or experimental agent concurrently with RT.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local Control (LC) | From randomization until local failure or last follow-up (up to 2 years) | Local control (LC), defined as the time from randomization to the date of local failure, after comprehensive clinical examination and radiographic evaluation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Locoregional Failure (LRF) | 2 Years | — |
| Distant Metastasis (DM) | 2 Years | — |
| Laryngectomy free survival (LFS) | 2 Years | — |
| Disease free survival (DFS) | 2 Years | — |
| Overall survival (OS) | 2 Years | Overall survival (OS) is defined as the time from the date of randomization to the date of death due to any cause. |
| Physician-assessed toxicities | 2 Years | National Cancer Institute (NCI) Common Terminology Criteria of Adverse Events (CTCAE) V.6, where higher grades indicate greater severity of toxicity. |
| Patient-reported toxicities | 2 Years | Patient Reported Outcomes - Common Terminology Criteria of Adverse Events (PRO CTCAE) V.1, where higher scores indicate greater symptom burden and worse patient-reported toxicity. |
| Quality of life (QOL) (UW-QOL) | 2 years | Head and Neck Cancer Specific QOL \[University of Washington Quality of Life Questionnaire (UW-QOL)\], where higher scores indicate a better quality of life. |
| Quality of life (QOL): Voice Handicap Index (VHI) | 2 Years | Voice Handicap Index (VHI): a patient-reported questionnaire that assesses the functional, physical, and emotional impact of voice disorders, where higher scores indicate greater voice-related handicap. |
| Quality of life (QOL): Swallowing-related quality of life [M.D. Anderson Dysphagia Inventory (MDADI)] | 2 Years | Swallowing-related quality of life \[M.D. Anderson Dysphagia Inventory (MDADI)\]: a patient-reported questionnaire assessing the impact of dysphagia on quality of life. Higher scores indicate better swallowing-related quality of life. |
| Financial Toxicity | 2 Years | Financial Index of Toxicity (FIT)\]: assesses the financial burden and impact of cancer treatment on patients. Higher scores indicate greater financial toxicity |
| Health Economics (EQ-5D-5L) | 2 Years | Cost-utility analysis using health utilization costs and health utility instruments (EQ-5D-5L), including lost productivity. Higher scores indicate better health-related quality of life. |
| Health Economics (HNC-8D) | 2 Years | Cost-utility analysis using health utilization costs and health utility instruments (HNC-8D), including lost productivity. Higher scores indicate better health status. |
Countries
Canada
Outcome results
None listed