Background
Role of radiotherapy in early glottic cancer
Toxicities of complete larynx radiotherapy
Complete larynx radiation field and larynx motion
Vocal-cord only irradiation
Methods/design
Study objectives
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Local control at 2-year after the end of RT.
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Patient-reported outcomes including dysphagia, voice impairment, and symptom burden.
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Acute and late toxicity radiation-induced toxicity
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OS and progression free survival (PFS)
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Acoustic and objective measures of voice analysis using the Consensus Auditory-Perceptual Evaluation of Voice.
Study design
Conditions for patient eligibility
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Age > 18 years
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Stage T1a-b N0 of the true vocal cords planned for definitive RT
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Patient not candidate for laser surgery or declined laser surgery
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Biopsy-confirmed squamous cell carcinoma, including verrucous carcinoma
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Eastern Cooperative Oncology Group (ECOG) performance status 0–2
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Ability to provide written informed consent.
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Ability to understand and read English or French at a level adequate for completion of patient reported outcomes questionnaires
Conditions for patient ineligibility
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Previous irradiation of the head and neck region
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Pregnancy or breastfeeding
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Any medical condition that represents, in the opinion of the investigator, a contraindication to radiotherapy or would prevent follow-up after radiotherapy.
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Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years.
Required pre-treatment evaluation
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History and Physical Examination, including:
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° Laryngoscopy, with detailed diagram of the primary lesion confirmed by both the radiation oncologist and head and neck surgeon
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° Biopsy of the primary tumor
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Patient reported outcomes questionnaires including the Voice Handicap Index 10 (VHI-10), the MD Anderson Dysphagia Inventory (MDADI) and the MD Anderson Symptom Inventory Head and Neck Module (MDASI-HN).
Intervention
Immobilization and simulation
Volumes
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CTVCL-RT = GTV plus a manual expansion superiorly to include the cranial arytenoid cartilage, inferiorly to include 1–1.5 cm below true vocal cords, anteriorly to include the anterior commissure, posteriorly to include posterior commissure and arytenoid cartilage.
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PTV CL-RT = 1 cm circumferential expansion around CTV CL-RT in all directions, except posteriorly where the margin will be 0.5 cm. As the PTV of CL-RT is based on previous fields of conventional RT, after the addition of a 1 cm margin, the PTV CL-RT should extend to the top of the thyroid cartilage lamina superiorly and to the bottom of the cricoid inferiorly; alternatively, the PTV CL-RT should be manually expanded.
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CTVVC-RT = GTV plus a manual expansion to include the entire ipsilateral vocal cord in stage T1a disease, or both vocal cords in stage T1b disease. In cases where the GTV is not visualized, only a CTV (comprising the entire involved vocal cord in T1a or both vocal cords in T1b) will be contoured.
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An internal target volume (ITV) will be added and will consist in an isotropic margin of 6 mm around the CTVVC-RT to account for respiratory motion.
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PTV VC-RT = ITV plus a 2–3 mm margin. This is smaller than in Arm 1, because internal motion is already accounted for in the ITV.
Dosimetry
Critical structures delineation and constraints
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Spinal cord: Not more than 0.03 cc of the planning organ at risk (PRV) exceeds 42 Gy and not more than 0.03 cc of the spinal cord receives > 40 Gy.
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Optimization of dose to other organs at risk (OAR) is not required. However, carotid-sparing is authorized.
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Spinal cord: Not more than 0.03 cc of the PRV exceeds 42 Gy and not more than 0.03 cc of the spinal cord receives > 40 Gy.
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Additional dose specification goals that should not take priority over PTV coverage:
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° Carotid arteries:
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▪ T1a
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Ipsilateral carotid: Mean dose < 35 Gy
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Controlateral carotid: Mean dose < 15 Gy
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▪ T1b
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Mean dose to carotids < 35 Gy
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° Supraglottic larynx: Mean dose < 45 Gy
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° Contralateral vocal cord: Mean dose < 50 Gy
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Doses to other organs should be minimized and documented.
IGRT
Study assessments
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There will be evaluation immediately post-treatment, as well as at 6, 12 and 24 months post-treatment as part of the study. Other follow-ups will be as per institution standard of care, but suggested schedule of assessments detailed in Table 1 is encouraged.
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Alternate follow-ups between the head and neck surgeon and the radiation oncologist will be mandatory.
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Physical examination will involve flexible laryngoscopy or/and videostrobe or/and mirror examination with adequate visualisation of vocal cords.
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Clinical follow-up will involve documentation of LC and survival status as well as reporting of CTCAE V4.03 toxicities.
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Patients will be asked to fill patient-reported outcome questionnaires at baseline and at each visit, as detailed in Table 1. The questionnaires will be administered in the following order: VHI-10, MDADI and MDASI-HN. The questionnaires could be filled in paper format, or online using the anonymized CASTOR EDC system. The questionnaires will not be reviewed during the study and will be analysed only at the pre-specified timepoints.
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There will be an optional assessment of acoustic and objective measures of voice analysis by a speech pathologist at baseline, immediately post-treatment and at 6 months post treatment. The assessments will consist in a digital recording of a standard oral reading passage and a short monologue, which would later be analyzed for specific acoustic variables and microacoustic measures of the cycle-to-cycle variation of acoustic parameters (in frequency and intensity domains). The voice quality will be graded as per then GRBAS scale (grade, roughness, breathiness, asthenia, strain).
Pre-RT | End of RT | 2moa | 6mo | 12 mo | 24 mo | 36moa | 48moa | 60moa | |
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History (including TIA or stroke) & physical exam (including laryngoscopy) | x | x | x | x | x | x | x | x | x |
Side effects | x | x | x | x | x | x | x | ||
TSHa | x | x | x | x | x | x | |||
Questionnaire VHI −10 | x | x | x | x | x | x | x | x | x |
Questionnaire MDADI and MDASI-HN | x | x | x | x | x | x | x | x | x |
Statistical considerations
Analytic plan
Data safety and monitoring board
Subject discontinuation / withdrawal
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Patient withdraws consent for participation. Subjects may voluntarily discontinue participation in the study at any time.
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It is deemed in the patient’s best interest as determined by the attending/principal investigator.