Background
Methods / design
Objectives
Study design
Primary endpoint
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Regional failure in the pN0 hemi-neck(s)
Secondary endpoints
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OS
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Disease-free survival (DFS)
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Local recurrence
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Regional recurrence
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Locoregional recurrence
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Rate of salvage treatment (surgery ± radiotherapy) in the pN0 neck, and freedom from unsalvageable neck recurrence
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QoL at 1 year, assessed with the MD Anderson Dysphagia Inventory (MDADI) [28], the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Cancer Patients general (QLQ-C30) [29] and head & neck (H&N35) scales [30], the EuroQOL 5-Dimension 5-Level (EQ-5D-5L) [31], and the Neck Dissection Impairment Index (NDII) [32]
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QoL measured at treatment completion and 6, 12, 15,18, 24, 30, 36, 42, 48, 54 and 60 months, measured with MDADI, EORTC QLQ-C30, H&N35, EQ-5D-5L and NDII
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Rate of feeding tube insertion after start of radiation (either gastric, gastrojejeunal, or nasogastric) and rate of feeding tube use at 1-year post-randomization.
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Toxicity, assessed using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03
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Rate of failure in the clinically node negative neck, if applicable (i.e. the undissected node-negative neck, for well-lateralized tumours).
Inclusion criteria
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Age 18 years or older
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Willing to provide informed consent
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Eastern Cooperative Oncology Group (ECOG) performance status 0–2
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Resected OCSCC with at least an ipsilateral selective neck dissection. The oral cavity includes: lips, buccal mucosa, oral tongue, floor of mouth, gingiva, retromolar trigone, and hard palate
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Patient has at least one pathological feature that is an indication for PORT: positive or close (≤ 3 mm) margin, presence of LVI or PNI, pT3 or pT4 disease, positive lymph nodes, or ENE
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PORT is recommended by the treating physician
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Pathologically lymph node negative in at least one dissected hemi-neck with at least 10 nodes recovered in each pN0 hemi-neck, after a dissection that at minimum includes nodal levels 1–3 in the pN0 hemi-neck(s).
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Radiation contours have been peer-reviewed and approved
Exclusion criteria
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Patients with an ipsilateral neck dissection only with positive lymph nodes, unless they undergo a contralateral neck dissection that is pN0
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Patients with bilaterally involved neck nodes
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Patients with pT3-T4 tumours involving midline who undergo an ipsilateral neck dissection (unless a contralateral neck dissection is performed)
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Serious medical comorbidities or other contraindications to radiotherapy
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Prior history of head and neck cancer within 5 years
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Any other active invasive malignancy, except non-melanotic skin cancers, low-risk prostate cancer, and Stage I-IVA papillary or follicular thyroid cancer.
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Prior head and neck radiation at any time
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Prior oncologic head and neck surgery in the oral cavity or neck.
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Known metastatic disease
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Locoregional disease recurrence identified following surgical resection but prior to start of radiotherapy
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Inability to attend full course of radiotherapy or follow-up visits
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Unable or unwilling to complete QoL questionnaires
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Pregnant or lactating women
Pre-treatment evaluation
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History and physical examination by a radiation oncologist within 5 weeks prior to randomization
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Staging prior to randomization:
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◦ CT or MRI of the neck (with contrast unless contraindicated) within 14 weeks of randomization. This can include the pre-operative CT, or the radiation therapy CT or MRI simulation if reviewed by a radiologist.
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▪ In some instances, suspicious lymph nodes are visible on the scan after surgery. In such instances, recurrence must be ruled out pathologically before enrollment, either with a needle biopsy or resection of these nodes.
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◦ CT of the chest or whole body PET-CT (usually prior to surgery, must be within 14 weeks of randomization)
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Histological confirmation of SCC
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Pregnancy test for women of child-bearing age within 2 weeks of randomization
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Dental evaluation prior to starting treatment, except edentulous patients
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Assessment of dysphagia using NCI-CTC version 4.03 within 2 weeks of treatment initiation
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Completion of QoL scoring prior to initiation of treatment
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Prior to randomization, radiation contours are to be peer-reviewed and approved
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MBS at baseline prior to initiation of treatment with documentation of the MBSIimP™©, DIGEST™ and the FOIS scores
Treatment plan
PTV Volume | CTV Volumes Included | Dose in 30 fractions | |
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Arm 1 | Arm 2 | ||
PTV64 Areas of positive margin or ENE | CTV64 | CTV64 | 64 Gy |
PTV60 Dissected neck | CTVp60 CTVn60pos CTVn60neg | CTVp60 CTVn60pos | 60 Gy |
PTV54 (optional) Not surgically dissected elective nodal regions | CTVn54pos CTVn54neg | CTVn54pos | 54 Gy |
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Prior to randomization, each set of contours will be peer-reviewed, either by another individual radiation oncologist or at a team head and neck QA rounds.
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All dose delivery for intensity-modulated plans (including arc-based treatments) will be confirmed before treatment by physics staff.
Participant discontinuation / withdrawal
Follow-up evaluation
Measurement of outcomes
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pN0 neck failure: measured as time from randomization until disease recurrence in the initially pN0 hemi-neck(s). Patients with prior or simultaneous recurrence at the primary site or in the initially pN+ hemi-neck will be censored for this outcome as of that timepoint. The primary endpoint is a comparison of pN0 neck failure in Arm 2 vs. historical controls; this endpoint will also be compared between the two arms as a secondary endpoint.
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OS: measured as time from randomization until death from any cause.
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DFS: measured as time from randomization to either recurrence at any location or death, whichever occurs first. New primary tumours will not count as DFS events.
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Local recurrence: measured as time from randomization until disease recurrence at the primary site.
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Regional recurrence: measured as time from randomization until disease recurrence anywhere in the neck.
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Locoregional recurrence: measured as time from randomization until disease recurrence anywhere in the neck or at the primary site, whichever occurs first.
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Recurrence in the pN0 neck without other locoregional recurrence: measured as time from randomization until disease recurrence in the pN0 neck alone without recurrence at the primary site or pN+ neck.
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Rate of salvage surgery and/or radiation in pN0 neck: measured as time from randomization to salvage intervention (surgery ± radiation) in the pN0 neck. Freedom from unsalvageable neck recurrence will be reported as the time from randomization to development of a neck recurrence in the pN0 neck that could not be salvaged.
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Feeding Tube Insertion: Rate of feeding tube insertion after start of radiation (either gastric, gastrojejeunal, or nasogastric) and rate of feeding tube use at 1-year post-randomization. Patients with feeding tubes inserted prior to randomization will be censored for this endpoint.
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Rate of failure in the clinically node negative neck: for patients who have unilateral neck dissections, the cN0 neck may be treated with radiation or observed, at the discretion of the treating oncologist (see section 6). This is measured as the time from randomization to failure in the cN0 neck, and will be reported for the whole group of patients who had unilateral dissections, and also stratified by whether radiation was delivered to that area.