VoiceS: Voice Quality After Transoral CO2-Laser Surgery Versus Single Vocal Cord Irradiation for Larynx Cancer (VoiceS)
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|ClinicalTrials.gov Identifier: NCT04057209|
Recruitment Status : Recruiting
First Posted : August 15, 2019
Last Update Posted : May 19, 2022
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.
|Condition or disease||Intervention/treatment||Phase|
|Glottis Tumor Larynx Cancer||Radiation: Single Vocal Cord Irradiation (SVCI) Procedure: Arm A: Transoral CO2-Laser Microsurgical Cordectomy (TLM)||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||34 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Masking Description:||The secondary phoniatric assessments will be carried out centrally by blinded phoniatricians.|
|Official Title:||VoiceS: Voice Quality After Transoral CO2-Laser Surgery Versus Single Vocal Cord Irradiation for Unilateral Stage 0 & I Glottic Larynx Cancer - A Randomized Phase III Trial|
|Actual Study Start Date :||November 20, 2019|
|Estimated Primary Completion Date :||November 30, 2025|
|Estimated Study Completion Date :||November 30, 2028|
Active Comparator: Arm A: Transoral CO2-Laser Microsurgical Cordectomy (TLM)
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)
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.
Experimental: Arm B: Single Vocal Cord Irradiation (SVCI)
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)
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.
- Voice Handicap Index [ Time Frame: 2 years ]average of the VHI scores (range: 0-120) of each patient up to 24 months after randomization
- Roughness - Breathiness - Hoarseness (RBH) [ Time Frame: 2 years ]The perceptual impression of a vocal signal remains the gold standard in phoniatric diagnosis. By means of reading the phonetically balanced text "The Rainbow Passage" in English and "Die Sonne und der Wind" in German, French and Italian (versions in different languages provided in the protocol), the speaking voice is assessed by the investigator according to the parameters roughness - breathiness - hoarseness (RBH), using the scale of 0: normal, 1: mild, 2: moderate, 3: severe. In this study, the assessment will be carried out blind.
- Jitter and shimmer (JS) [ Time Frame: 2 years ]JS are regarded as objective, quantitative characteristics of voice quality. They describe the variations in the fundamental note of a vocal signal. Jitter is the variation of the cycle-to-cycle frequency in held vowels (in Hz or. %, norm = 0-3%), shimmer is the cycle-to-cycle variation in the amplitude of held vowels (in dB, or. %, norm = 0-20%). In this study, the assessment will be carried out blind.
- Glottal-to-Noise Excitation Ratio (GNE) [ Time Frame: 2 years ]GNE serves to describe the relationship of the voice signal to the noise signal (norm = 1-0) and is also a quantitative characteristic of voice quality. Jitter, shimmer and GNE correspond to the perceptual characteristics roughness - breathiness - hoarseness. In order to carry out jitter, shimmer and GNE, the test subjects hold the vowel /a/ mezzoforte for at least 5 seconds at their average speaking pitch. The vocal samples will be recorded and subsequently evaluated using the open source freeware software Praat (http://www.fon.hum.uva.nl/praat/ by Paul Boersma and David Weenink - Phonetic Sciences, University of Amsterdam Spuistraat 210 1012VT Amsterdam, Netherlands). In this study, the assessment will be carried out blind.
- Singing Power Ratio (SPR) [ Time Frame: 2 years ]The 'brilliant' sound of a voice is characterized in acoustic terms by a high degree of acoustic energy above 2 kHz. This can be calculated with the aid of the SPR. In the Fast-Fourier-Transformation, the amplitudes of the highest peaks between 2 and 4 kHz and of the highest peaks between 0 and 2 kHz are determined using a vocal sample and the one subtracted from the other. The lower the SPR, the more "sonorous" is the voice. For this, the test subjects hold the vowel /a/ mezzoforte for at least 5 seconds at their average speaking pitch. The vocal samples will be recorded and subsequently evaluated using Praat. In this study, the assessment will be carried out blind.
- Loco-regional control of the disease [ Time Frame: 5 years ]
Event: loco-regional failure after randomization
The time-to-event outcome loco-regional control will be evaluated using Kaplan-Meier curves and a Cox model adjusted for the randomization stratification factors.
- Toxicity / Morbidity [ Time Frame: 5 years ]
Treatment toxicity up to 5 years (based on CTCAE v.5.0) after randomization
Treatment toxicity up to 5 years will be summarized descriptively for each group, showing the overall number of events as well as number and percentage of patients with events.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04057209
|Contact: Olgun Elicin, M.D.||+41 31 632 26 firstname.lastname@example.org|
|Contact: Timo Nannen||+41 31 63 2 90 email@example.com|
|Lausanne, Vaud, Switzerland|
|Contact: Jean Bourhis, MD +41 21 314 46 66 firstname.lastname@example.org|
|Contact: Mahmut E Ozsahin, MD +41 21 314 46 03 email@example.com|
|Principal Investigator: Jean Bourhis, MD|
|Sub-Investigator: Mahmut E Ozsahin, MD|
|Inselspital, Bern University Hospital||Recruiting|
|Bern, Switzerland, 3010|
|Contact: Olgun Elicin, MD +41 31 632 26 32 firstname.lastname@example.org|
|Contact: Timo Nannen email@example.com|
|Principal Investigator: Olgun Elicin, MD|
|Genève University Hospital||Recruiting|
|Contact: Francesca Caparrotti, MD +41 79 553 56 12 firstname.lastname@example.org|
|Contact: Laurence Zulianello Laurence.Zulianello@hcuge.ch|
|Principal Investigator: Francesca Caparrotti, MD|
|Principal Investigator:||Olgun Elicin, M.D.||Inselspital, Bern University Hospital, 3010 Bern, Switzerland|