InGReS: Intra-treatment Image Guided Adaptive Radiotherapy Dose-escalation Study
- Conditions
- Head and Neck Cancer
- Interventions
- Radiation: Intra-treatment Image-Guided Adaptive Radiotherapy Dose-escalation
- Registration Number
- NCT05393297
- Lead Sponsor
- Guy's and St Thomas' NHS Foundation Trust
- Brief Summary
InGReS is a phase I pilot study of adaptive dose-escalated radiotherapy in combination with platinum-based chemotherapy (CRT) for locally advanced head and neck cancer.
InGReS will assess the feasibility of adapting the radiotherapy (RT) plan for each patient, based on anatomical and metabolic changes in the tumour seen on MRI and FDG-PET-CT performed after 2 weeks of CRT in a multicentre setting. The overall aim of the trial is to determine the safety and feasibility of delivering dose-escalated Intensity Modulated Radiotherapy (IMRT) to the residual primary tumour, as seen on intra-treatment imaging, in the final 3 weeks of RT.
- Detailed Description
The study will recruit 15 patients with locally advanced oropharyngeal or hypopharyngeal squamous cell carcinoma (SCC) who are suitable for primary treatment with concurrent chemo-radiation. The main aim is to see whether it is feasible to perform a FDG positron emission tomography-computed tomography (FDG-PET-CT) and Magnetic Resonance Imaging (MRI) scan after 2 weeks of radiotherapy and re-plan the radiotherapy to escalate the dose of radiotherapy delivered to the residual primary tumour as seen on PET-CT and MRI.
Patients will commence with standard chemo-radiotherapy; 70 Gray (Gy) in 35 fractions with concomitant platinum chemotherapy. After 2 weeks of chemo-radiotherapy patients will have an intra-treatment FDG-PET-CT and MRI scan to assess early response to treatment. Patients with evidence of residual disease will proceed with the dose-escalation phase of the study, with an adaptive radiotherapy re-plan and dose-escalation to the residual primary tumour.
The study will establish acute and late radiotherapy toxicity rates in patients who receive dose-escalated RT, particularly the effect of treatment on long-term swallowing function. The study hypothesis is that mucosal toxicity rates for dose-escalated treatment will be equivalent to those for standard CRT, according to published data. Furthermore, it will also explore whether changes in FDG-PET-CT and MRI during treatment correlate with patient outcomes and potential blood-based biomarkers of treatment response. Local control, disease-free and overall survival will be assessed for both standard and dose-escalated approaches.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 15
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description HNSCC receiving (chemo)radiotherapy Intra-treatment Image-Guided Adaptive Radiotherapy Dose-escalation Radiation: Intra-treatment FDG-PET-CT and MRI will be used to identify tumours and patients for dose-escalation. Patients identified for dose-escalation (boost) will undergo adaptive radiotherapy replanning, with the primary tumour (GTVp) receiving 76.9Gy in 35 fractions.
- Primary Outcome Measures
Name Time Method To assess the safety of delivering an additional 10% dose (biological rather than numerical) of radiotherapy to the residual primary tumour during radiotherapy 12 months Incidence of grade 3 or above late Radiation Therapy Oncology Group (RTOG) and European Organization for Research and Treatment of Cancer (EORTC) mucosal toxicity or feeding tube retention rate following completion of treatment. An excess rate of \>14% would be regarded as unacceptable.
- Secondary Outcome Measures
Name Time Method Incidence of grade 3 or above late non-mucosal toxicity (RTOG/EORTC) 12 months Toxicity of non-mucosal late toxicity will be graded using Radiation Therapy Oncology Group (RTOG) and European Organization for Research and Treatment of Cancer (EORTC) late toxicity scoring. Scores will be presented at 13 weeks; 6 and 12 months after treatment. Grading scale: 0-5, with the higher score meaning a worse outcome.
Incidence of grade 3 or above late non-mucosal toxicity (NCI CTCAE) 12 months Toxicity of non-mucosal late toxicity will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events scale v.5.0. Scores will be presented at 13 weeks; 6 and 12 months after treatment. Grading scale: 0-5, with the higher score meaning a worse outcome.
Incidence of grade 3 or above late non-mucosal toxicity (LENT/SOMA criteria) 12 months Toxicity of non-mucosal late toxicity will be graded using the modified Late Effects on Normal Tissues- Subjective, Objective, Management, Analytic (LENTSOMA) scoring systems. Scores will be presented at 13 weeks; 6 and 12 months after treatment. Grading scale: 0-4, with the higher score meaning a worse outcome.
To assess swallowing panel measurements including qualitative swallowing assessments (MDADI) 12 months M.D. Anderson Dysphagia Inventory (MDADI) scores will be plotted over time. Scores will be presented at baseline and weeks 3 \& 7 of CRT. Then at 13 weeks; 6 and 12 months after treatment. A higher MDADI score represents better function and quality of life.
To assess patient reported outcomes measures and quality of life questionnaires (EORTC QLQ-C30 and EORTC QLQ-H&N43) 12 months Patient reported outcomes measures and quality of life scores, using the questionnaires of the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Modules 30 and 43 (EORTC QLQ-C30 and EORTC QLQ-H\&N43), will be plotted over time. Scores will be presented at baseline and weeks 3 \& 7 of CRT. Then at 13 weeks; 6 and 12 months after treatment.
For the functioning and the quality of life scales, a higher score indicates better health. For the symptoms scales, a higher score indicates a higher level of symptom burden.To assess results of quantitative swallowing assessments (Videofluoroscopy) 12 months Video-fluoroscopy test scores, particularly the Rosenbek Penetration/Aspiration Scale (PAS) and the summary Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scores, will be presented at 12 months after treatment. For both PAS and summary DIGEST scores, a higher score indicates worse function.
Incidence of grade 4 acute mucosal toxicity (NCI CTCAE) 12 weeks Toxicity grading, using National Cancer Institute Common Terminology Criteria for Adverse Events scale v.5.0, will be presented during and up to 12 weeks after treatment. Grading scale: 0-5, with the higher score meaning a worse outcome.
To assess patient reported outcomes measures and quality of life questionnaires (UW-QOL v 4.1) 12 months Patient reported outcomes measures and quality of life scores using the University of Washington Quality of Life Questionnaire (UW-QOL) v4.1 will be plotted over time. Scores will be presented at baseline and weeks 3 \& 7 of CRT. Then at 13 weeks; 6 and 12 months after treatment. A higher score represents better function and quality of life.
To assess late toxicity rates and the effect of treatment on swallowing function (100ml water swallow) 12 months 100ml water swallow test results will be presented at baseline. Then at 6 weeks, 13 weeks, 6 months and 12 months after treatment. Patients will be reported as having failed the test if they coughed or had a wet voice quality post swallow or were unable to finish the task.
To assess tumour response to adaptive radiotherapy dose-escalation (FDG-PET-CT) 3 months Complete metabolic response rate on PET-CT scan will be reported at 3 months after treatment
The loco-regional tumour control 12 months Incidence of local or regional tumour recurrence rates will be presented.
Disease-free survival 12 months Disease-free survival rates (Kaplan-Meier estimates) will be presented at 3 and 12 months after completion of CRT.
Overall survival 12 months Overall survival rates (Kaplan-Meier estimates) will be presented at 3 and 12 months after completion of CRT.
Trial Locations
- Locations (1)
Guy's and St Thomas' NHS Foundation Trust
🇬🇧London, United Kingdom