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

Table 1 Summary flowchart

Study periods	Screening and enrollment	Treatment period	Follow-up until 60 months after enrollment
Time unit	Days	Weeks	Months
Patient information and informed consent	− 28–0
Medical history and demographics	− 28–0
Panendoscopy, assessment of exposure, and staging according to institutional local standards	− 28–0
Eligibility criteria check	− 28–0
ESGC-oriented physical examination	− 28–0
VHI^a, RBH, GNE, SPR, JS	− 28–0		(1.5)^a, 6, 12, 18, 24 (+/− 15 days)
Enrollment and randomization^b	0
Endoscopic assessment of the index tumor, symptom-oriented physical examination	− 28–0		Every 3 months (+/− 15 days) until 24th month every 6 months (+/− 15 days) between 24th and 60th months
Evaluation of actual smoking status and toxicity according to CTCAE v.5.0 (see Additional file)	− 28–0 (baseline smoking status and toxicity^c)	weekly during radiotherapy and within one week of surgery: no need to document except for SAEs
Pregnancy test for women with child-bearing potential	− 28–0	3–7^d	Until 3rd month^d
Arm A: transoral CO₂-laser microsurgical cordectomy^e		day of surgery +/− day of re-resection
Arm B: single vocal cord irradiation		3 (16 fractions)

GNE glottal-to-noise excitation ratio, JS Jitter and Shimmer, RBH roughness – breathiness – hoarseness, SAEs serious adverse events, ESGC early-stage glottic cancer, SPR singing power ratio, VHI voice handicap index
^aVHI at 6 weeks after the end of treatment (regardless of study arm) will be assessed to evaluate the need for phoniatric rehabilitation, but not as a study-specific outcome measure (i.e., primary endpoint) to avoid lead time bias. Patients with a VHI > 14 will be advised to undergo a phoniatric rehabilitation, but the examiner should not try to persuade the patient. Similarly, any VHI >14 at any follow-up time point or patients’ requests justify the need for phoniatric rehabilitation, which will be recommended to the patients regardless of study arm. No need to record the VHI in the CRFs
^bEven if done on the same day, patient enrollment shall be done after the completion of the necessary documentation
^cThe baseline toxicity scores and smoking status may be documented after the accrual but it must be done before the start of trial treatment
^dIf clinically indicated
^eThe treatment shall start within 28 days post-accrual

ISSN: 1745-6215