VoiceS: Voice Quality After Transoral CO2-Laser Surgery Versus Single Vocal Cord Irradiation for Larynx Cancer

NCT04057209 | Recruiting DMC

• 1 other identifier: KEK-BE 2019-01506
• Study Type: interventional
• Target: 34
• Locations: 3 countries
• Sites: 4

Brief Summary

Laser surgery and radiotherapy are well-established standards of care for unilateral stage 0 \& I carcinoma in situ (Cais) and squamous cell carcinoma of glottic larynx (SCCGL). Based on meta-analyses, functional and oncological outcome after both treatment modalities are comparable1-5. However, no properly conducted randomized trials comparing these treatments exist. The only such trial with the endpoint of voice quality had to be prematurely closed due to low accrual6. The traditional radiotherapy involves the treatment of the whole larynx. Recently, a new radiotherapy technique was introduced by a team of researchers from Netherlands, where the treated target volume consists of involved vocal cord and therefore 8 to 10-fold smaller than the target volumes used for traditional whole larynx irradiation. The treatment is reduced to 16 fractions which corresponds to 3 weeks and a day7-12. The results of a prospective cohort (n=30) with single vocal cord irradiation (SVCI) were compared with the results of a historical prospective cohort previously treated with whole larynx radiotherapy (n=131) in the same institute. The median follow-up was 30 months. The voice handicap index (VHI) at all time points beginning from the 6th week after SVCI was significantly superior to the same time points with conventional radiotherapy. Moreover, a comparable local control with SVCI (100%) vs. conventional radiotherapy (92%) was reported at two years, p=0.2412. Based on this information, the investigators' main aim is to compare SVCI to Transoral CO2-Laser Microsurgical Cordectomy (TLM) with the main focus of patient-reported voice quality.

Conditions

Glottis Tumor; Larynx Cancer

Keywords

head and neck cancer; squamous cell carcinoma; carcinoma in situ; radiotherapy; surgery; transoral laser microsurgery; patient reported outcome; quality of life; voice

Outcome Measures

Primary Outcomes (1)

• Voice Handicap Index

  average of the VHI scores (range: 0-120) of each patient up to 24 months after randomization

  up to 2 years

Secondary Outcomes (7)

• Roughness - Breathiness - Hoarseness (RBH)

  6, 12, 18, and 24 months

• Jitter and shimmer (JS)

  6, 12, 18, and 24 months

• Glottal-to-Noise Excitation Ratio (GNE)

  6, 12, 18, and 24 months

• Singing Power Ratio (SPR)

  6, 12, 18, and 24 months

• Loco-regional control of the disease

  2 and 5 years

Study Arms (2)

Arm A: Transoral CO2-Laser Microsurgical Cordectomy (TLM)

ACTIVE COMPARATOR

Transoral CO2-Laser Microsurgical Cordectomy defined by European Laryngological Society (Remacle M, Eckel HE, Antonelli A, et al. Endoscopic cordectomy. A proposal for a classification by the Working Committee, European Laryngological Society. Eur Arch Otorhinolaryngol. 2000;257(4):227-231.)

Procedure: Arm A: Transoral CO2-Laser Microsurgical Cordectomy (TLM)

Arm B: Single Vocal Cord Irradiation (SVCI)

EXPERIMENTAL

Single Vocal Cord Irradiation defined by Kwa et al. and Al-Mamgani et al. (Kwa SLS, Al-Mamgani A, Osman SOS, Gangsaas A, Levendag PC, Heijmen BJM. Inter- and Intrafraction Target Motion in Highly Focused Single Vocal Cord Irradiation of T1a Larynx Cancer Patients. Int J Radiat Oncol Biol Phys. 2015;93(1):190-195. Al-Mamgani A, Kwa SLS, Tans L, et al. Single Vocal Cord Irradiation: Image Guided Intensity Modulated Hypofractionated Radiation Therapy for T1a Glottic Cancer: Early Clinical Results. Int J Radiat Oncol Biol Phys. 2015;93(2):337-343.)

Radiation: Single Vocal Cord Irradiation (SVCI)

Interventions

Single Vocal Cord Irradiation (SVCI) RADIATION

The following planning aim will be pursued: full coverage of the PTV with at least 95% of the prescribed dose and a maximum (0.03 cc) PTV dose of \<107%: 16 x 3.63 = 58.08 Gy in 5 fractions per week using 5 to 9 static IMRT or VMAT.

Arm B: Single Vocal Cord Irradiation (SVCI)

Arm A: Transoral CO2-Laser Microsurgical Cordectomy (TLM) PROCEDURE

The TLM has to be performed using a CO2 laser, coupled to an operative microscope, at 4-8W in ultrapulse mode. The type of cordectomy performed must be mentioned using the following classification according the classification of the European Laryngological Society. The type of resection chosen should provide complete removal of the primary lesion with negative margins. Surgery will generally be performed within 3 weeks after randomization and not more than 6 weeks after panendoscopy. The extent of the cordectomy must include a complete anterior, posterior, inferior and supero-lateral mucosal and deep soft tissue margin.

Arm A: Transoral CO2-Laser Microsurgical Cordectomy (TLM)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ECOG performance status 0-1 at the time of registration
• ≥18 years of age
• Baseline assessments and documentation of voice quality by means of VHI, JS, RBH, GNE, SPR
• Histopathologically confirmed, previously untreated unilateral (cT1a or unilateral cTis) stage 0 or I glottic larynx cancer based on the UICC staging system (8th edition)
• History and physical examination by treating physician (head and neck surgeon and radiation oncologist) within 28 days prior registration
• The patient must be expected to withstand both study interventions
• The patient must have undergone panendoscopy with assessment for the feasibility of transoral exposure for resection. Patients without feasible exposure are not eligible
• Localization of the tumor should allow resection with a minimum of 2 mm macroscopical margin without extension to the contralateral vocal fold, without partial resection of the arytenoid cartilage and without resection of parts of thyroid cartilage (Cordectomy Type I-IV according the classification of the European Laryngological Society)13
• Hemoglobin ≥10 g/dL or 6.2 mmol/L (Note: The use of transfusion to achieve Hgb ≥10 g/dL is acceptable) within the 28 days prior to accrual
• Written informed consent, signed by the patient and the investigator.

You may not qualify if:

• Infection hampering the voice quality at the time of voice assessment
• Involvement of the anterior commissure by the tumor
• Previous oncologic surgery with curative intent (exception: excisional biopsies resulting in unacceptable close R0 or R1/R2 margins may be included) or radiotherapy to larynx
• Synchronous or previous malignancies. Exceptions are adequately treated basal cell carcinoma or SCC of the skin, or in situ carcinoma of the cervix uteri, low-risk prostate cancer or breast with a cancer-free follow-up time of at least 3 years, or other previous malignancy with a progression-free interval of at least 5 years
• Co-existing disease prejudicing survival (expected survival less than 6 months)
• Active bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• History of any voice disorders (not related to the SCCGL) lasting longer than 3 weeks
• Illness requiring hospitalization or precluding study therapy within 28 days before registration
• Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Sponsors & Collaborators

• Olgun Elicin: lead
• University of Bern: collaborator
• The Netherlands Cancer Institute: collaborator
• University of Lausanne Hospitals: collaborator
• University Hospital, Geneva: collaborator
• University of Zurich: collaborator

Study Sites (4)

Institut Gustave Roussy

Paris, 94805, France

RECRUITING

Tata Memorial Hospital Mumbai

Mumbai, Maharashtra, 400012, India

RECRUITING

Inselspital, Bern University Hospital

Bern, Canton of Bern, 3010, Switzerland

RECRUITING

University Hospital Zurich

Zurich, Canton of Zurich, 8091, Switzerland

RECRUITING

Related Publications (1)

• Reinhardt P, Giger R, Seifert E, Shelan M, Riggenbach E, Terribilini D, Joosten A, Schanne DH, Aebersold DM, Manser P, Dettmer MS, Simon C, Ozsahin EM, Moeckli R, Limacher A, Caparrotti F, Nair D, Bourhis J, Broglie MA, Al-Mamgani A, Elicin O. VoiceS: voice quality after transoral CO2 laser surgery versus single vocal cord irradiation for unilateral stage 0 and I glottic larynx cancer-a randomized phase III trial. Trials. 2022 Oct 27;23(1):906. doi: 10.1186/s13063-022-06841-5.

  PMID: 36303192 DERIVED

MeSH Terms

Conditions

Laryngeal Neoplasms; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Carcinoma in Situ

Condition Hierarchy (Ancestors)

Otorhinolaryngologic Neoplasms; Neoplasms by Site; Neoplasms; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Otorhinolaryngologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Study Officials

• Olgun Elicin, M.D.

  Inselspital, Bern University Hospital, 3010 Bern, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Olgun Elicin, M.D.

CONTACT

+41 31 632 26 32; olgun.elicin@insel.ch

Timo Nannen

CONTACT

+41 31 63 2 90 74; timo.nannen@insel.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The secondary phoniatric assessments will be carried out centrally by blinded phoniatricians.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator and Sponsor

Study Record Dates

• First Submitted: August 7, 2019
• First Posted: August 15, 2019
• Study Start: November 20, 2019
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2030
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 1 year after the peer-reviewed publication of all primary and secondary endpoints.

Locations

CH (2); FR (1); IN (1)