The PEARL study will recruit approximately 50 patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) who are about to undergo primary treatment with concurrent chemo-radiation from South Wales (Velindre Cancer Centre and Singleton Hospital, Swansea) and Bristol. The main aim is to see whether it is feasible to preform a positron emission tomography-computed tomography (PET-CT) scan after 2 weeks of radiotherapy and re-plan the radiotherapy based on this PET-CT scan, to re-distribute the dose of radiotherapy being delivered, so that a smaller area of normal tissues in the mouth and throat are treated to a high dose of radiotherapy.
PEARL is a prospective, interventional, non-randomised, phase II feasibility study for patients with good prognosis Human Papillomavirus (HPV)-associated oropharyngeal squamous cell cancer (OPSCC) who are suitable for treatment with concurrent chemo-radiotherapy (CCRT). The incidence of oropharyngeal squamous cell carcinoma (OPSCC) caused by Human Papillomavirus (HPV) infection (HPV-positive OPSCC) is increasing in the United Kingdom. It tends to affect younger patients and has a better outcome than most other head and neck cancers. A large proportion of patients diagnosed with HPV-positive OPSCC will undergo non-surgical treatment. This usually involves 6 to 7 weeks of chemo-radiotherapy, with chemotherapy being given weekly or during the first and fourth week of the radiotherapy course (CCRT). Many patients with HPV-positive OPSCC are cured of their disease but often have to live for several decades with the side effects of their treatment. Side effects from radiotherapy are usually caused because normal tissues surrounding the cancer receive radiation whilst the cancer itself is being treated. Positron emission tomography-computed tomography (PET-CT) scans are able to look at the metabolic (or biological) activity of cells and are currently recommended in the UK for response assessment after a patient has completed radiotherapy for a head and neck cancer but, as far as we know, have not yet been used routinely to adapt radiotherapy according to the individual patient's response during radiotherapy. PEARL will explore the feasibility of individually adapting the radiotherapy plan for each patient after 2 weeks of radical CCRT, based on biological changes in tumour activity seen on an interim FDG-PET-CT scan, carried out early on during a course of treatment. The aim is to reduce the dose of radiotherapy received by surrounding normal tissues to ultimately reduce toxicity. The study will establish the progression free survival rate (PFS) in patients who receive biologically adapted radiotherapy. Furthermore, it will also explore whether changes seen on PET-CT scan during treatment correlate with outcome and with changes in potential blood-based biomarkers of response. Toxicity rates will be assessed, particularly the effect of treatment on swallowing function.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Patients will have three scans during the trial. * The 1st scan (prePET) is a baseline diagnostic scan. The patient is in a thermoplastic shell and PET CT will be used by to define a bGTV\_P. bGTV\_P will then be used as an adjunct to help us delineate the GTV\_P. * The 2nd scan (iPET) takes place following 2 weeks (10 fractions) of chemo-radiotherapy. The patient is in a thermoplastic shell and the PET CT will be used to delineate the remaining avid disease (bGTV\_iP). * The 3rd scan takes place 3 months following the last dose of radiotherapy. It will be used to ascertain whether any avid disease remains and may inform the need for further treatment.
The biological GTVs (bGTV\_P and bGTV\_iP) will be automatically delineated by ATLAAS and verified manually by a nuclear medicine physician and a clinical oncologist. It will consist of the high FDG uptake volume based on visual assessment whilst using suitable windowing levels. Any differences in contouring will be settled either by the two doctors reaching a consensus or by a third doctor if differences between the first two cannot be resolved.
In order to contribute to our understanding of how disease processes may be monitored in a less invasive and less morbid manner, we will be collecting blood and saliva samples prior to, during, and after the radical treatment of OPSCC in PEARL, to see if there is correlation with disease status and FDG-PET-CT response.
In order to contribute to our understanding of how disease processes may be monitored in a less invasive and less morbid manner, we will be collecting blood and saliva samples prior to, during, and after the radical treatment of OPSCC in PEARL, to see if there is correlation with disease status and FDG-PET-CT response.
Velindre Cancer Center at Velindre Hospital
Cardiff, Wales, United Kingdom
Singleton Hospital
Swansea, Wales, United Kingdom
University Hospitals Bristol NHS Foundation Trust
Bristol, United Kingdom
Progression free survival at 2 years
To maintain a high progression free survival rate with biologically adapted radiotherapy in patients with good prognosis HPV positive OPSCC. To be certain that we are not having a negative impact on PFS by adapting the RT plan we will ensure that PFS is at least as high as expected after treatment with chemo-radiotherapy in patients with similarly staged HPV-positive OPSCC.
Time frame: 2 years following enrolment
Monthly recruitment rate
As this is a feasibility study, recruitment will be monitored and monthly recruitment rate over 2 years will be presented.
Time frame: End of 2 years recruitment period
To test if individualized, adaptive, biologically-based radiotherapy planning is feasible and results in a significant change in the radiotherapy plan.
Percentage reduction in mean dose to OAR (superior pharyngeal constrictor muscles, contralateral parotids, contralateral submandibular gland, salivary glands) as a result of PET-CT during treatment. Percentage change to PTV will also be presented.
Time frame: 2 weeks (10 fractions) of chemo-radiotherapy
To test if individualized, adaptive, biologically-based radiotherapy planning results in a significant change in the radiotherapy plan.
Percentage reduction in mean dose to OAR (superior pharyngeal constrictor muscles, contralateral parotids, contralateral submandibular gland, salivary glands) as a result of PET-CT during treatment. Percentage change to PTV will also be presented.
Time frame: 2 weeks (10 fractions) of chemo-radiotherapy
To maintain high complete response rates 3 months after treatment
The proportion of patients who are complete metabolic responders at 3 months as per PERCIST criteria will be presented.
Time frame: 3 months post treatment
Acute toxicity rates
Cumulative acute CTCAE toxicity score percentages during and up to 3 months after treatment will be presented.
Time frame: 3 months post treatment
Late toxicity rates
Water swallow test will be plotted over time, scores will be presented at 6, 12, 18 and 24 months.
Time frame: 6, 12 and 24 months post treatment
Late toxicity rates
MDADI will be plotted over time, scores will be presented at 6, 12, 18 and 24 months.
Time frame: 6, 12 and 24 months post treatment]
Late toxicity rates
QoL scores will be plotted over time, scores will be presented at 6, 12, 18 and 24 months.
Time frame: 6, 12 and 24 months post treatment]
To assess the effect of treatment on swallowing function
Water swallow test scores will be plotted over time.
Time frame: 3, 6, 12 and 24 months post treatment
To assess the effect of treatment on swallowing function
MDADI scores will be plotted over time.
Time frame: 3, 6, 12 and 24 months post treatment
To assess the effect of treatment on swallowing function
QoL scores will be plotted over time.
Time frame: 3, 6, 12 and 24 months post treatment
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