Changes to Function and Quality of Life and Patient Experience for Patients Undergoing Treatments for Recurrent Oropharyngeal Cancer
Conditions: Recurrent Oropharynx Carcinoma
Sponsor: Royal Marsden NHS Foundation Trust

 
 
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Study Protocol  
Study title: Changes to function and quality of life and patient experience for patients undergoing 
treatments for recurrent oropharyngeal cancer CCR5242.  
Short Title: FUNQOLR (FUNctiional and QOL changes with Recurrent oropharyngeal cancer) 
 
Chief Investigator: 
Professor Vinidh Paleri 
Principal Investigator: 
Professor Vinidh Paleri 
Co-investigators: 
Grainne Brady, Dr Justin Roe, Dr Mary Wells, Professor Pernilla 
Lagergren 
 
Sponsor: The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ 
Management: The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ 
Academic Host: Imperial College London. 
 
Protocol Reference: 
CCR5242  
Version Number & Date:  
V6.0 22.5.2024 
 
Superseded Version 
Number & Date (If 
applicable) 
V5.0 28.02.2023 
 
 
 
 
 
 
 

 
 
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Contents Page 
Contents Page .................................................................................................................. 2 
1. 
Background ............................................................................................................ 3 
2. 
Rationale ............................................................................................................... 5 
3. 
Aims....................................................................................................................... 5 
4. 
Study Design .......................................................................................................... 6 
5. 
Study objectives ..................................................................................................... 6 
6. 
Study end points..................................................................................................... 7 
7. 
Inclusion/ exclusion criteria .................................................................................... 8 
8. 
Methodology ......................................................................................................... 9 
9. 
Data Acquisition ................................................................................................... 11 
10. 
Sample size .......................................................................................................... 15 
11. 
Data analysis ....................................................................................................... 15 
12. 
Patient and public involvement ............................................................................ 16 
13. 
Study organisation/ Trial Monitoring and Management Strategy ......................... 17 
14. 
Safety reporting ................................................................................................... 19 
15. 
Regulatory & Ethics Committee Approval ............................................................. 19 
16. 
Data handling and record keeping ........................................................................ 20 
17. 
Financing, Indemnity & Insurance ......................................................................... 20 
18. 
Publication policy ................................................................................................. 21  
19. 
Abbreviations ....................................................................................................... 22 
20. 
References ........................................................................................................... 23 
Appendix 1: Performance Status Scale in Head and Neck cancer standard operating 
procedure (SOP) ............................................................................................................. 26 
Appendix 2: IDDSI Functional Diet Score: SOP .................................................................. 28 
Appendix 3: 100ml Water Swallow Test (100ml WST) SOP ............................................... 30 
Appendix 4: Dynamic Imaging Grade of Swallowing Toxicity for Fibreoptic Endoscopic 
Evaluation of Swallowing (FEES-DIGEST) SOP .................................................................. 33 
Appendix 5: Protocol Version History .............................................................................. 34 
 

 
 
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1. Background 
Approximately 9000 patients are treated for head and neck cancer (HNC) by the NHS every year 
(Paleri et al 2018). There has been a dramatic increase in oropharyngeal cancer (OPC) over the past 
15 years and this in part is due to the rise in Human Papilloma Virus (HPV) related disease (Schache 
et al 2016). Non-HPV related OPC, which is traditionally associated with a history of smoking and 
alcohol, is also increasing in the UK (Schache et al 2016). This trend is predicted to continue with an 
expected 50% rise in HNC cases over the next 20 years (Louie et al 2015).  
 
Primary OPC is treated with curative intent using (chemo) radiation, surgery or a combination of 
these treatment modalities (NICE, 2016). Dysphagia is one of the most profound side-effects of HNC 
and/or its treatment, with swallowing ability being a priority concern for patients up to one year 
following treatment (Roe et al 2014). Dysphagia is an independent predictor of survival and is 
associated with higher risk of pneumonia, poorer oral intake, prolonged gastrostomy use, poor 
nutritional status and weight loss as well as fundamental changes to eating patterns, social life, and 
subsequent quality of life (QoL) (Patterson et al 2016). Speech can also be affected by the presence 
of a tumour or the treatments received in particular surgical management and this can have a 
devastating impact on a person’s psychosocial well-being, participation in social and occupational 
roles and overall QoL (Clarke et al 2016).  
 
Despite advances in various treatment modalities, the overall prognosis of HNC patients has not 
improved significantly within the last several decades and advanced tumours have a recurrence rate 
of 20–30% at the primary tumour site (Mandapathil et al 2014). Patients may present with residual 
disease (diagnosed within 12 months of initial treatment) or recurrent disease (diagnosed within 5 
years of initial treatment) (Hardman et al, 2020). In addition to residual/ recurrent disease, patients 
with HNC are also over 11 times more likely than the general population to develop a second 
primary head and neck cancer (Chuang et al 2008). For patients with second primary HNC disease, 
this typically occurs in a previously irradiated field including the primary disease site and/or neck and 
in the radical or adjunctive setting (Hardman et al 2020). Due to the complexity of further treatment 
in any form, patients with residual, recurrent and new primary disease in a previously irradiated 
field, are considered a homogenous cohort (Paleri et al 2020) and for the purposes of this document 
will be referred to as patients with recurrent OPC.  
 
Recurrent OPCs present some of the most challenging management issues in head and neck surgical 
and oncological practice. Surgery or re-irradiation may be the only hope for locoregional disease 
control however these treatments may have substantial implications for communication and 
swallowing function and overall QoL (Mehanna et al, 2016). As a result, the majority of these 
patients are either treated with palliative intent including chemotherapy, immunotherapy, clinical 
trial entry or receive best supportive care (Mehanna et al, 2016). However, recent literature has 
suggested that survival outcomes are improving for patients with recurrent OPC. A recent meta-
analysis shows that the outcomes in cases of OPC recurrence appear to have improved significantly 
over the last two decades, reaching five-year survival of 50 per cent in patients treated surgically 

 
 
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(Jayaram et al, 2016). Improved survival may be the result of a combination of factors including 
patient selection, advances in surgical care and the role of HPV as a distinct aetiological factor 
(Mehanna et al, 2016).  
 
The aim of surgical resection in the recurrent setting, also referred to as salvage surgery, is complete 
macroscopic clearance of the recurrent tumour with wide clear margins which can result in large 
defects which require reconstruction (Mehanna et al 2016). This can have a significant functional 
impact on communication and swallowing and overall QoL (White et al, 2013). The consequential 
large functional deficits must be balanced against the benefit of longer survival (Mehanna et al, 
2016). Open salvage surgery for recurrent OPC has been associated with a high complication rate 
with 48% patients experiencing poor healing and prolonged hospital stays (Zafereo et al 2009). 
Successful resection of OPC recurrence can be difficult due to the complex three-dimensional 
anatomy and proximity and adherence to the internal carotid artery (Mehanna et al 2016). Access 
procedures through mandibulotomy (jaw split) or lingual release (lip split) are usually required and 
in the setting of previous radiotherapy this can increase the risk of osteoradionecrosis, in addition to 
extensive disruption to the oral cavity and floor of mouth musculature (Hamilton & Paleri, 2017). 
Recent advances in transoral robotic surgery (TORS) have facilitated transoral access to the 
oropharynx avoiding the need for mandibulotomy or lingual release (Hamilton & Paleri, 2017). The 
use of this minimally invasive surgical approach is now being extended to the treatment of recurrent 
OPC (Paleri et al 2020). A recent multicentre case control study showed that salvage patients treated 
with transoral robotic surgery had a significantly lower incidence of tracheostomy, feeding tube use, 
and shorter hospital stay, with significantly decreased incidence of positive margins and significantly 
higher survival than matched patients treated with open surgery (White et al 2013). Favourable 
outcomes in terms of swallowing recovery have also been reported (Paleri et al 2020).  
 
In the era of highly conformal radiotherapy techniques such as intensity-modulated radiotherapy 
(IMRT), there may be opportunities for re-irradiation, however this is associated with toxicity and 
has the potential to further compound pre-existing treatment related effects including swallowing 
function (Brady et al, 2020).   
 
Patients receiving best supportive care have an average overall survival of four months after 
diagnosis (Mehanna et al 2016). As per national guidelines, patients with non-resectable recurrent 
OPC being considered for palliative systemic treatments should be offered the opportunity to 
participate in clinical trials of new therapeutic agents (Mehanna et al 2016). Triple therapy with 
platinum, cetuximab and 5-fluorouracil (5-FU) (EXTREME regimen) appears to provide the best 
outcomes for the management of patients with recurrence who have a good performance status 
and are fit to receive chemotherapy (Mehanna et al 2016). In a large multisite retrospective review 
including 733 patients across 71 sites, for patients treated with platinum-based combinations, 
overall survival was 8 months (95% CI: 7.0 – 8.0), with 1-year survival reaching only 30.9% (95% CI 
27.5 – 34.3) (Grünwald et al 2020). More recently, however, the results of the KEYNOTE-048 study 
have shown that selected patients experience better survival outcomes and less toxicity with single- 
agent pembrolizumab or combined pembrolizumab-chemotherapy when compared with the 
EXTREME regimen (Burtness et al 2019).  

 
 
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National guidance recommends that patients with recurrent HNC should undergo appropriate and 
extensive counselling regarding expected survival and functional outcomes for treatments for 
recurrent disease (Mehanna et al, 2016). However, empirical multidimensional functional outcome 
data is not available for these patients and such data may aid treatment decision making if there are 
particular concerns regarding function. Given ongoing advancements in the treatment options for 
recurrent OPC with evidence of improved survival outcomes, these patients are now living longer. 
However, not only are they living with the well documented treatment effects of their primary 
treatment (Roe et al 2014), these difficulties are now potentially compounded and exacerbated by 
further radical surgery, re-irradiation or systemic and targeted therapies. 
 
 
2. Rationale 
To enable people to make informed choices about the range of treatments available for recurrent 
OPC, detailed information is required on the likely trajectory of functional and QoL change during or 
following treatment. Patient experience data is essential for any research so that relevant QoL 
endpoints can be identified, appropriate outcome data can then be collected and thus meaningful 
data can be presented to patients during the decision-making process (Blanchard et al 2016). This 
project will aim to address the gaps in the literature with regards to both functional and QoL 
outcome data and patient/ carer experience of the functional changes in communication and 
swallowing and overall QoL during and following treatments for recurrent OPC. 
 
The purpose of this study is to understand the lived experience of being diagnosed and living with 
recurrent head and neck cancer and how functional and QoL changes are prioritised by patients. This 
study will also measure the  trajectory of swallowing, communication and QoL change for people 
undergoing treatments for recurrent OPC.  
 
 
3. Aims 
1. To report on functional and QoL outcomes for patients who undergo treatments for 
recurrent OPC including surgery (open or TORS), re-irradiation, palliative systemic or 
targeted therapies.   
2. To describe patient and carer experience of recurrent OPC and priority concerns with 
regards to function and QoL.  
 
 

 
 
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4. Study Design 
This study is an exploratory observational design.  
This study will comprise of two work streams including:   
1. Part A: prospective non-randomised, non-interventional descriptive observational cohort 
study 
2. Part B: a non-interventional, non-randomised longitudinal qualitative descriptive interview 
study using thematic analysis 
Please see figure 1 for study schema. 
Population 
Part A: patients with biopsy proven residual, recurrent or new primary OPC in a previously irradiated 
field.  
Part B: patients with biopsy proven residual, recurrent or new primary OPC in a previously irradiated 
field, and their carers.  
 
5. Study objectives 
The primary objective of the study is to measure change in swallowing function over time for 
patients receiving treatment for recurrent OPC which will be evaluated by a patient-reported 
outcome (PRO) using the MD Anderson Dysphagia Inventory (MDADI) (Chen et al 2001) comparing 
change from baseline to 6 months.   
Secondary objectives for the study are to:  
1. Investigate potential changes in function for  up to 6 months using  
(i) 
The Performance Status Scale for Head and Neck Cancer (PSS- HN) scale 
(normalcy of diet, eating in public and understandability of speech scales) (List 
et al 1990) 
(ii) 
the 100 mL Water Swallow Test (100ml WST) (Patterson et al 2011) 
(iii) 
the International Dysphagia Diet Standardisation Initiative (IDDSI) functional diet 
score (Steele et al 2018) 
(iv) 
Fibreoptic Endoscopic Evaluation of Swallowing Dynamic Imaging Grade of 
Swallowing Toxicity (FEES DIGEST) grade (Starmer et al, in press) 
2. Assess patient-reported QoL and priority concerns using the University of Washington 
Quality of Life (UW-QoL) questionnaire (v.04) (Rogers et al 1999) 

 
 
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3. Assess patient-reported priorty concerns at baseline and 6 months using the Chicago Priority 
Scale (CPS) (Sharp et al 1999) 
4. Report on gastrostomy tube usage up to 6 months  
5. Report on survival status up to 6 months 
6. To explore patient and carer priority concerns with regards to function and QoL and how 
these concerns may influence decision making regarding treatment options using semi 
structured interviews 
 
Figure 1: Study schema 
 
 
  
 
 
6. Study end points 
Primary and secondary endpoints for Part A non-interventional descriptive observational cohort 
study are as follows: 

 
 
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Primary endpoint  
Difference in the mean MDADI composite score at baseline compared to 6 months after surgical 
treatment or re-irradiation or 6 months into non-surgical treatment  
Secondary endpoints 
1. MDADI composite score at baseline and 3 and6, months following surgical or re-irradition 
treatment or 3 and 6, months into non-surgical treatment.  
2. Mean PSS-HN Normalcy of diet, public eating and speech intelligibility using the PSS-HN 
scale scores at 3 and 6 months .  
3. Median (IQR) IDDSI functional diet score International dysphagia diet standardisation 
initiative functional diet scale (IDDSI-FDS) at baseline and 3 and 6 months following surgical 
or re-irradition treatment or 3 ad 6,months into non-surgical treatment.  
4. Mean 100ml WST capacity score score at baseline and 3 and 6,  months following surgical or 
re-irradition treatment or 3 and 6 months into non-surgical treatment.  
5. FEES DIGEST summary score at baseline and 3 and 6 months following surgical or re-
irradition treatment or 3 and 6months into non-surgical treatment.  
6. Mean UW-QoL4 composite physical, social and functional scores at baseline and 3 and6  
months following surgical or re-irradition treatment or 3 and6 months into non-surgical 
treatment.  
7. Number and percentage of patients ranking of  CPS categories (1-12) in order of importance, 
at baseline and  6  months following surgical or re-irradition treatment or 6 months into 
non-surgical treatment  
8. Number and percentage of patients still alive at the end of the study  
9. Number and percentage of patients using a gastrostomy at each time point at baseline and 3 
and6 months following surgical or re-irradiation treatment or 3 and6 months into non-
surgical treatment.  
 
 
 
 
7. Inclusion/ exclusion criteria 
Please see table 1 for inclusion/ exclusion criteria for patient participants in Part A and Part B: 
Table 1: Inclusion/ exclusion criteria Part A and B (patient participants)  
Inclusion criteria 
Exclusion criteria 
• 
Adult (aged 18 years or over) and 
competent to provide consent  
• 
Any previous medical condition, other 
than HNC, which has a known impact 

 
 
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• 
Have a diagnosis of recurrent OPC 
• 
Have adequate linguistic and cognitive 
function to participate in interview 
• 
English speaking 
on communication/ swallowing 
(Parkinson’s Disease, Multiple Sclerosis, 
cerebral vascular accident (CVA)  
 
 
Please see table 2 for inclusion/ exclusion criteria for carers in Part B:   
Table 2: Inclusion/ exclusion criteria carers Part B 
Inclusion criteria 
Exclusion criteria 
• 
Be carers of patients 18 years or over 
who have been diagnosed with 
recurrent OPC  
• 
Have adequate linguistic and cognitive 
function to participate in interview  
• 
English speaking 
• 
They do not fulfil all of the inclusion 
criteria  
 
 
Number of participants 
Part A:  44 retrospective participants will be recruited. Please see section 10 for detailed description 
of statistical plan including sample size calculation.  
Part B: Expected recruitment rates include approximately 20-30 patients (10-15 
retrospectivepatients and 10-15 prospective patients) and 10-20 carers (5-10 carers of retrospective 
patients and 5-10 carers of prospective patients) or until data saturation occurs- please see data 
analysis plan in section 11.  
 
8. Methodology 
Identification of patients 
Sequential patients who are referred to RM for management of newly diagnosed recurrent OPC will 
be identified from the weekly head and neck multidisciplinary team meeting. Those patients 
identifying all of the inclusion criteria and who are invited to an appointment at the Royal Marsden 
will be sent an initial letter of invitation prior to their appointment. At their appointment they will be 
approached to take part in the study.  
 
Patients who have undergone surgery at least 12 months ago or who have commenced palliative 
treatments within the last 12 months will be identified from outpatient clinic lists and will be invited 
to take part in semi structured interviews investigating their experience of being diagnosed with and 

 
 
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treated for recurrent OPC. Carers/ family members of the person with recurrent OPC will also be 
invited to take part in an interview. Participant identification centres (PICs) will also be used as part 
of the recruitment strategy for the study. These centres will identify potential participants through 
database searches and direct these patients to the recruiting site for participation.  
Sampling 
Purposive sampling will be used to try and recruit patients who are undergoing/undergone the 
various treatment options available- open surgery, TORS, re-irradiation, palliative systemic 
treatments, to ensure that there is a range of patients, both male and female, with representation 
across a range of ethnic and socioeconomic backgrounds for both Parts A and B of the study.   
Informed consent 
Potential participants who are receiving care at the Royal Marsden will receive a letter of invitation 
prior to their next scheduled appointment highlighting that they may be approached about the 
study in advance of their appointment.  
 
At the patients next scheduled outpatient appointment; which may be virtualor face-to-face, their 
usual care team will introduce the trial with the patient. PICs will also identify potential participants 
through database searches and direct these patients to the recruiting site for participation. If the 
patient expressed an interest in being involved, they will be provided with a Patient Information 
Sheet (PIS) which will include a telephone number and contact email. Patients identified by PICs will 
be advised to contact the research team using the contact details included in the PIS. Appropriate 
time will be given to patients and carers to read and digest the information on the PIS. The potential 
participant may be asked to provide informed consent following a minimum of 1 hour to read the 
PIS and consider participation. Potential participants will be offered video call facilities to discuss 
potential participation with their family friend/ relative if they wish. 
 
During the COVID19 pandemic, national guidelines have advised to minimise face-to-face contact 
with patients and recommended remote consultations. As such, both during the pandemic and for 
the remainder of the trial, this consent consultation may either be a face-to-face or telephone / 
video consultation. For participants identified and recruited via PICs – remote consent only will be 
obtained.  
 
If a remote consent consultation is held patient identification using date of birth and address will be 
checked during this process. Where possible, there will be two members of the clinical team present 
for this consultation; one member taking consent and another member present as a witness; 
however, this is not mandatory for the consent process. 
 
If the patient is eligible, they will be invited to voluntarily provide informed consent to participate in 
this study. Consent will be taken by a member of the research team/ speech & language therapy 
team/ research nurse under the supervision of the PI. If the consultation is being conducted face-to-
face then consent will be obtained in-person with wet ink signature on the consent form. For remote 

 
 
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telephone / video consultations, verbal consent will be sought and clearly documented in the 
patients’ medical notes. The patient will also be asked to sign a consent form which can be returned 
to the study team via:  
• 
Post 
• 
Email (the patient should bring the original wet ink copy to their next hospital appointment)  
• 
In person at the patients next face-to-face hospital appointment 
 
Where a patient has been remotely consented, upon receipt of the original wet-ink consent form it 
will be signed by the member of staff who had discussed the study with the patient and obtained the 
verbal consent.  
 
At the next possible in-person visit with the RM patient the study team member who carried out the 
remote consent should countersign the consent form in the presence of the patient. The patients’ 
medical records should be updated to document the entire consent process.  
 
A copy of the signed ICF along with a copy of the PIS will be given to the study participant.  An 
original signed & dated consent form will be scanned and uploaded to the Electronic Patient Record 
(EPR) for RM patients and a copy will be placed in the investigator site file (ISF). 
Subject withdrawal criteria 
A participant can withdraw from the study at any time. No further data will be collected but data 
previously collected will still be used.  Participants will be made aware that their overall medical care 
will not be affected if they choose not to participate/withdraw from the study at any time.  
 
 
9. Data Acquisition   
Part A 
Following informed consent, patients will have all functional and QoL measures collected at their 
next scheduled outpatient appointment. No additional outpatient appointments or patient contacts 
will be required for RM patients. All patients are routinely seen by the clinical team at baseline, and 
for regular follow up including 3 and 6 month clinical reviews, where all measures except the 
Chicago Priority Scale (CPS) will be repeated. The CPS will be completed at baseline and 6 months 
only.  In the event that social distancing measures remain in place and patients are not attending the 
hospital for face-to-face review with their clinical team, or if the patient has a preference for remote 
review, and for participants identified via PICs, a video consultation will be set up so that a minimum 
set of outcome measures can be collected including the MDADI, and UWQoL4, PSS- HN (all 
domains), Functional IDDSI Diet Score, CPS and the 100ml WST.  
The only measure which cannot be obtained via remote means is the FEES assessment. Please see 
figure 2 for data acquisition schema.  
 

 
 
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Figure 2: Data acquisition process Part A (face-to-face) 
 
 
Table 3: Data acquisition process Part A (remote consultation) 
 
 
Please see below a description of each data collection tool:  
1. The MDADI is a validated and reliable self-administered questionnaire for evaluating the 
impact of oropharyngeal dysphagia on QoL in HNC patients. The questionnaire consists of 20 
questions. Patients rate their responses to statements included on the MDADI on a 5-point 
scale from “strongly agree” to “strongly agree”. There are 5 subscales. The first is a single, 
global subscale question to understand the impact of swallowing problems on quality of life. 
The other subscales address emotional, functional, and physical problems. The global 
question is scored individually and the other subscales are scored and the mean score is 
calculated. The mean score is then multiplied by 20 to calculate the composite total score 
which can range from 0, indicating very low functioning, to 100, indicating extremely high 
functioning. 
2. The PSS-HN is a clinician rated instrument where each subscale (Normalcy of Diet, Eating in 
Public and Speech Intelligibility) is rated from 0 to 100, with higher scores indicating better 
performance. The PSS-HN has been shown to have good inter-rater reliability and sensitivity 
to differences in performance and change over time. See appendix 1 for standard operating 
procedure.  
3. The IDDSI functional diet score is a clinician rated measure of dysphagia severity based on 
the degree of diet texture restriction. See appendix 2 for standard operating procedure.  
4. The 100ml WST is a simple, repeatable measure of swallowing efficiency. This measure has 
been previously validated in the head and neck population, and the quantitative measures 
derived from this test, can be used as a measure of swallow performance over time. Patients 
are asked to drink 100ml of water as quickly and as comfortably as possible- swallow 
volume, capacity and speed are calculated by timing the test and counting the number of 
swallows completed by the participant. See appendix 3 for standard operating procedure.  
5. The DIGEST-FEES  is a rating scale used to report on swallowing safety and efficiency as 
observed during a Fibreoptice Endoscopic Evaluation of Swallowing (FEES). FEES is an SLT led 
Patient self-
administered/ reported
• MDADI 
• UW-QOL V4.0
• CPS
Clinician- reported
• PSS-HN
• Functional IDDSI Diet 
Score
Clinical examination
• 100ml WST
• FEES-DIGEST
Patient self-
administered
• MDADI 
• UW-QOL V4.0
• CPS
Clinician- reported
• PSS-HN
• Functional IDDSI Diet 
Score
Clinical examination
• 100ml WST

 
 
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endoscopy procedure which involves the use of a fibreoptic scope which is passed 
transnasally into the participant’s pharynx by a trained SLT. The patient is given some food 
and liquids so that swallowing function can be measured in terms of swallowing safety and 
swallowing efficiency. The summary DIGEST rating aligns with National Cancer Initiative’s 
framework for toxicity reporting in oncology trials and assigns a global rating of pharyngeal 
swallowing function according to the interaction of the safety and efficiency profile scores. 
See appendix 4 for standard operating procedure.  
6. The UW-QOL v4.0 is a validated QoL tool examining 12 QoL domains including pain, 
appearance, activity, recreation, swallowing, chewing, speech, shoulder function, taste, 
saliva, mood and anxiety. In this tool, each question is scaled from 0 (worst) to 100 (best) 
according to the hierarchy of response. It also has two global questions about their health- 
related and overall QoL. In addition, it is possible to calculate a composite score of physical 
and social-emotional functioning (Rogers et al 1999). The UW-QOL questionnaire is a self-
administered scale and each of the categories has several options within it that allow the 
patient to describe their current functional status. Patients also have the opportunity to 
select up to 3 options from the 12 domains that are most important to them. The 
questionnaire relates to the previous 7 days.  
7. The CPS  is a previously validated tool to assess patients’ priorities among potential 
functional outcomes following treatment for head and neck cancer. Participants will be 
given a list of 12 statements; including ‘being cured of my cancer’, ‘living as long as possible’, 
‘having no pain’, ‘being able to swallow all foods and drinks’, ‘having a normal amount of 
energy for me’, ‘returning to my activities as soon as possible’, ‘having my speech 
understood easily’, ‘keeping my natural voice’, ‘having a comfortably moist mouth’, ‘keeping 
my appearance unchanged’, ‘being able to chew normally’ and ‘keeping my normal sense of 
taste and smell’. Patients will be asked to rank each priority from 1-12 where the most 
important priority is ranked number 1 and the least important number 12.  
 
The multi-dimensional outcome measures will include all routine measures of swallowing function 
used at our centre currently. The UW-QOL V4.0 and CPS assessment will be in addition to standard 
of care assessment by the SLT team.  
 
Please see table 4 for data acquisition plan:  
Table 4: data acquisition time points part A 
Timepoint 
Measure 
Domain 
Endpoint 
Baseline, 3, and 6  
months 
MDADI 
Swallowing related 
QoL 
Composite score 
UW-QoLv4 
Health related QoL 
Composite scores of 
physical and social-
emotional functioning 
are derived from 12 
domains. Patients can 
also highlight up to 3 

 
 
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priority concerns from 
the previous 7 days  
PSS-HN 
Normalcy of Diet, 
Eating in public and 
speech intelligibility  
Score for each subset 
100ml WST 
Swallowing function 
Swallowing capacity 
score (mls/second)  
Functional IDDSI diet 
score 
Diet modification 
Diet score (1-8) 
FEES- DIGEST (only if 
patient is attending 
for a face-to-face 
appointment 
Swallowing toxicity 
rating 
Summary score (0-4)  
Baseline & 6 months 
Chicago priority scale 
Patient priority rating 
of treatment 
outcomes 
Ranked 1-12 priorities 
 
Part B 
Following informed consent, a proportion of the sample in Part A (prospective cohort), a number of 
patients who have undergone surgery at least one year ago/ or commenced palliative treatments 
within the past 12 months (retrospective cohort) and also carers from both patient cohorts will be 
invited to take part in interviews via video consultation. The interview with patients/ carers will take 
place at a time that is convenient to both the patient and carers. Participants to be included in Part B 
will also be identified via PICs.  
 
For the prospective patient cohort who are also participating in part A of the study the interview will 
take place after the measures have been collected in Part A on a day which is convenient to the 
participants. Semi-structured interviews will be completed with a member of the research team and 
will include a number of questions detailed in the topic guide directed towards the research aim in 
order to promote discussion and identify key swallowing, communication and QoL priorities and 
concerns. The topic guide has been developed from previous literature and via consultation with the 
project’s Patient-Public Steering Group (please see section 13 on PPI). For the prospective cohort the 
interview will be completed at baseline and again at 6 months following or into treatment.   
 
For the retrospective cohort the interview will take place for both patient and carers at a single 
timepoint at least 12 months post surgery or within 12 months of commencing palliative treatments.  
 
The interviews will take place remotely either via telephone or video consultation. The interviews 
will be anonymised and transcribed verbatim. Please see section 11 for description on how the data 
will be analysed.  
 
 

 
 
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10. 
Sample size  
Part A  
Part A: The sample size calculation is based on the primary endpoint, change in MDADI scores from 
baseline and 6 months following diagnosis/treatment of recurrent disease. Previous data has shown 
that a 10-point between-group difference in MDADI score is clinically significant (Hutcheson et al 
2016). This end point has not been measured systematically previously in recurrent disease  
patients. 
 
Pilot data collected at the Royal Marsden Hospital  available  for a service evaluation was used  to 
look MDADI score in this cohort of patients.  Data based on 10 patients  shows a mean composite 
score of 66.50 at baseline  and 52.60 at 6 months  with a standard deviation of the difference of 
23.68.  
 
With a two-sided alpha of  5%  and 95% power a total of  40  participants will be required to 
complete the paired questionnaires at baseline and 6 months post-treatment (power function, 
STATA). An additional 4 patients will be recruited to cover for 10% drop out for a total sample of 44 
patients. Seventy-five patients are referred to the Royal Marsden Hospital per year with recurrent 
OPC and this number is set to increase with the on-going developments in robotic surgery, 
experimental trials and the development of the International Centre for Recurrent Head and Neck 
Cancer (IReC). Data collection will take place over an 18-month period.  
Part B 
Given that this study is qualitative and exploratory, a sample size calculation is not required. 
Expected recruitment rates include approximately 20-30 patients and 10-20 carers or until data 
saturation occurs- please see data analysis plan in section 11.  
 
 
 
11. 
Data analysis 
A consort flow diagram will be produced to describe the flow of patients through the study 
Part A 
 
Baseline patient characteristics (age, gender, ethnicity and previous HNC treatment history) will be 
summarized in addition to the diagnostic and treatment details (site of recurrence, type of 
treatment, use of reconstruction, tracheostomy, feeding tube presence/ type) using descriptive 
statistics.  
 

 
 
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The primary endpoint data will be analysed to compare the mean change from baseline MDADI 
composite score to 6 months into or post treatment using a two-sided paired t-test if data are 
normally distributed. In the eventually of not normally distributed data  non-parametric-methods 
(Wilcoxon Signed Rank test) will be used. 
 
Secondary endpoints (PSS, 100ml WST, IDDSI functional diet score, FEES-DIGEST and UW-QOL,and 
CPS scores ) will be summarised  using summary statistics (mean with standard deviation if data are 
normally distributed or median with IQR if data have a skewed distribution). 
Counts and percentages will be presented with 95% confidence intervals. 
Part B 
Framwork theamatic analysis (Iliffe et al 2015) will be used to analyse the qualitative data using 
NVivo software. The 5 key stages of framework analysis will be used as follows: 
1. Familiarisation: data will be sensitised into early themes, individual difference within and 
between transcripts will be identified 
2. Identifying a thematic framework: key themes, issues and discussion points will be identified 
and given a code/ label 
3. Indexing: transcripts will be annotated numerically in order to identify a consistent coding 
framework 
4. Charting: the final coding framework wil be synthesised and developed 
5. Mapping and interpreting: the main themes identified from the data will be represented 
pictorially/ graphically to  demonstrate how they interact with and relate to each other 
 
 
12. 
Patient and public involvement 
This research proposal was presented to the Patient and Carers Research Review Panel at the Royal 
Marsden Hospital on 16.1.2019. This group included two HNC patients, one of whom has recurrent 
disease, carers and lay volunteers. The NIHR Research Design Service (RDS) Enabling Involvement 
Fund was also awarded to the research team to further involve patients and carers in the design of 
this study. Using this initial funding a small group of patients who have undergone treatment for 
recurrent OPC were invited as a PPI research steering group specific to this project.  A meeting with 
this group was held on 22.2.2019. Two of the patients attended and a further four provided 
feedback and advice remotely.  The research proposal was presented for discussion. This research 
has also been discussed with Mr Chris Curtis, Chair of the Swallows Head and Neck Cancer Charity. 
Opinions were sought on the research idea/question and the data collection methods including 
interviews and proposed functional outcome measures. 
The PPI groups explained the following:  
• 
The research question was ‘important’ and ‘worthwhile’ and commented on the importance 
of capturing information about functional outcomes ‘I would have found information on 

 
 
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speech and swallowing very helpful in my decision making...I didn’t have that information 
and that was what I was worried about’  
• 
It was crucial to use interviews in addition to functional outcome measures, as ‘not all 
information can be captured by clinical tools’  
• 
Carers should be included as interviewees, as key functional concerns and QoL concerns will 
impact carers too. They explained that communication and eating and drinking ‘is social’ 
involving ‘more than just the patient’ and that ‘patients and families “hear” different things’, 
‘the diagnosis, treatment and aftermath have such an impact on the family as a whole’.  
• 
The outcome measures outlined in the research proposal were ‘acceptable’, including 
objective measures which are sometimes ‘reassuring’; ‘I seem to be able to tolerate 
nasendoscopy fairly well and find it helpful and reassuring to know what is going on with my 
swallow’.  
The research protocol was delayed due to the pandemic however co-investigator kept in touch with 
the core PPI group of patients with a history of recurrent OPC and they continue to work with GB on 
an ongoing basis with ongoing research planning. At a recent meeting (17.3.21) the primary and 
secondary objectives and endpoints were revised and approved by the group. The topic schedule for 
the qualitative study was also developed. The ethics application was also discussed and advice 
sought on timing of informed consent and any potential psychological distress which might happen 
as a result of the data collection. The group once again highlighted that having the measures taken 
may be ‘reassuring’ and that the interviews may ‘give a chance to have your voice heard’. 
 
Wider PPI was sought in March 2021 to review the informed consent form (ICF) and participant 
information sheet (PIS) using the RM PPI database. 
 
PPI plans throughout the research and dissemination phases are as follows (to be completed 
remotely via email and videoconferencing): 
• 
Recurrent OPC PPI group now extablished (6 members). We have agreed 6 monthly virtual 
meetings with 6 weekly email updates. PPI involvement will include interpretation of results, 
planning for and write up of results including co-authorship, co-presenting and liaison with 
charities (for example The Swallows) and patient groups.  
• 
Wider PPI involvement will also be sought using the RM/BRC digital voices platform- an 
overview and eventually the findings of the study will be presented here.  
• 
The overall findings of the study will be presented back at the Patients and Carers review 
committee to seek further ideas/ advice on dissemination to patient/ carer groups.  
13. 
Study organisation/ Trial Monitoring and Management 
Strategy 
Responsibilities 
Name 
Professor Vinidh Paleri 

 
 
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Role(s) 
Principal investigator & Chief investigator 
Responsibilities 
Oversight of project design, conduct and reporting.  
Liaison with Research Ethics Committee (REC), and other review bodies, during 
the application process, and where necessary during, the conduct of the 
research. 
Ensure adherence to protocol.  
 
 
 
Name 
Dr Justin Roe 
Role(s) 
Co-investigator 
Responsibilities 
Oversight of the clinical outcome data collection.  
Quality assurance.  
Ensure adherence to protocol. 
 
 
Name 
Grainne Brady 
Role(s) 
Co-investigator 
Research Fellow 
Responsibilities 
Screening and recruitment including informed consent 
Data collection: CRF, functional and quality of life outcomes 
Data collection: qualitative interviews 
Statistical analysis of quantitative findings 
Thematic analysis of qualitative findings 
Project write up and dissemination  
 
Name 
Professor Pernilla Lagergren 
Role(s) 
Co-investigator  
Responsibilities 
Ensure adherence to protocol.  
Support analysis of patient reported outcome  
 
 
 
Name 
Professor Mary Wells 
Role(s) 
Co-investigator  
Responsibilities 
Ensure adherence to protocol. 
Oversight of qualitative methodology.  
 
 
 
 
 

 
 
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Data quality checks  
Part A: One of the co-investigators who is not involved in the data collection will check the accuracy 
of 10% of all of the anonymised data entered into the excel spreadsheet.  
Part B: One of the co-investigators will review 10% of the anonymised interview transcripts to verify 
coding process.  
Timeline 
The protocol will be submitted for scientific review by the Committee for Clinical Research and for 
local management R&D approval and REC. The PI/CI will be notified in writing of the CCR/ R&D 
Approval. The study will then be activated on the Hospital Information System and the PI/CI will be 
notified that the study is open for recruitment. This date will be classified as start date for the R&D 
database. 
 
The data collection period will continue for 18 months or until 44 patients have been recruited and 
longitudinal data obtained and 15-20 patients and 12-15 carers have taken part in 2 interviews at 
baseline and 6 months.  
 
14. 
Safety reporting 
This is a non-invasive study involving routine clinical assessments of function and validated 
questionnaires designed to identify the presence and symptoms of dysphagia/ communication 
difficulties and the impact on QoL. Due to the non-interventional nature of the study, adverse events 
will not be recorded.  
 
The participant may present with a dysphagia. If dysphagia is identified, referral for SLT assessment 
will be made and the medical team and G.P. informed. Other issues may also arise such as 
compromised nutritional status or psychological distress. If such issues arise appropriate referrals 
will be initiated following liaison with the medical team i.e. Dietitian referral, Psychological Support 
etc.  
 
Participation in interviews/ questionnaires may cause potential upset or emotional distress. The 
participant’s cancer key worker (Head and Neck CNS) will be aware of the patient’s participation and 
will be available to provide psychological support in the event that the participant becomes upset.   
 
 
15. 
Regulatory & Ethics Committee Approval 
The study will be reviewed by the Committee for Clinical Research (CCR) and the Health Research 
Authority (HRA).  HRA approval conditions will be followed. 
 
 

 
 
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16. 
Data handling and record keeping 
All data will be handled in accordance with the UK General Data Protection Regulation (UK GDPR) 
and the Data Protection Act 2018. The CRFs will not bear the participant’s name or other directly 
identifiable data. The participant’s study Identification Number (PIN) only, will be used for 
identification. The Subject PIN log will be used to cross reference participant’s identifiable 
information. All data from the paper CRFs and questionnaires will be collected in an excel 
spreadsheet using PINs only.  
 
The ISF and excel spreadsheet, will be stored at the Royal Marsden NHS Foundation Trust. All data 
will be coded and no identifiable reference to the participants will be held with the data. Paper CRFs 
and questionnaires and interview transcripts will be stored in locked, fireproof file cabinets.  Coded 
data held electronically will be stored on password protected NHS computers. In the event of 
remote working, the secured RM sharedrive can be accessed and used by members of the research 
team employed by the Royal Marsden.   Anonymised audio interview data will be transferred 
securely to an external transcription service.  
 
The investigator site file will include ICFs, questionnaire response forms, and CRFs. The 
questionnaire responses and CRFs will not bear identifiable information as the anonymous study 
identification (PIN) number will be used. The ICFs will be stored securely separate to the anonymised 
data in a locked fire proof filing cabinet held in the SLT department at the Royal Marsden Hospital.  
 
The Royal Marsden NHS Foundation Trust will permit study-related monitoring, audits, REC review, 
and regulatory inspection(s), providing direct access to source data/documents. Participants are 
informed of this during the informed consent discussion. Participants will consent to provide access 
to their medical notes
 
 
17. 
Financing, Indemnity & Insurance  
This study will form part of a PhD training fellowship, being undertaken at Imperial College London 
by a student who is employed by the Royal Marsden NHS Foundation Trust, as Clinical Lead Speech 
and Language Therapist. The Clinical Doctoral Research Fellowship has been funded by the National 
Institute of Health Research. The study is supported by The Royal Marsden NHS Foundation Trust.  
Where the Royal Marsden NHS Foundation Trust is either sponsoring or collaborating with externally 
sponsored research the NHS Litigation Authority will cover standard clinical negligence by 
employees, staff and health professionals employed by the Royal Marsden NHS Foundation Trust. 
For more information visit the following website:  
http://www.nhsla.com/Claims/Pages/Clinical.aspx.  
There is unlimited liability and no excess. Insurance is provided under the Clinical Negligence 
Scheme for Trusts and there is no cover for non-negligence claims. 
 

 
 
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18. 
Publication policy 
The PI is responsible for approving the content and distribution of all publications, abstracts and 
presentations arising from the study and for assuring the confidentiality and integrity of the study. 
The data arising from the project will belong to the RMH and will be retained and stored securely 
with the Royal Marsden NHS Foundation Trust for a period of 5 years.  
 
Any communication arising from this research that enters the public domain, including publications, 
press releases, websites, presentations, posters and participant materials correctly acknowledge the 
NIHR and use the new NIHR identity and will acknowledge support from the BRC.   
 
Publication: “Any activity that discloses, outside of the circle of trial investigators, any final or interim 
data or results of the study or any details of the study methodology that have not been made public 
by the Sponsor including, for example, presentations at symposia, national or regional professional 
meetings, publications in journals, theses or dissertations.” 
 
All scientific contributors to the study have a responsibility to ensure that results of scientific interest 
arising from Trial are appropriately published and disseminated. The Sponsor has a firm 
commitment to publish the results of the Trial in a transparent and unbiased manner without 
consideration for commercial objectives.  
 
To maximise the impact and scientific validity of the study, data shall be consolidated over the 
duration of the trial, reviewed internally among all investigators and not be submitted for 
publication prematurely.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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19. 
Abbreviations 
Acronym Meaning 
CCR 
Committee for clinical research 
CI 
Chief investigator 
CRF 
Case report form 
GCP 
Good clinical practice 
HNC 
Head and neck cancer 
HPV 
Human papilloma virus 
IRAS 
Integrated research application system 
ISF 
Investigator site file 
MDADI 
M. D. Anderson Dysphagia Inventory 
MDT 
Multidisciplinary team 
OPC 
Oropharyngeal cancer 
PI 
Principal investigator 
PPI 
Patient and public involvement 
PIN 
Patient identification number 
PSS-HN 
Performance status scale for head and neck cancer 
QoL 
Quality of life 
R&D 
Research and development 
REC 
Research ethics committee 
RM 
Royal Marsden 
SLT 
Speech & Language Therapist/Therapy 
SOP 
Standard operating procedure 
UWQoL4 University of Washington Quality of Life Questionnaire 
WST 
Water swallow test 
 
 

 
 
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20. 
References 
Blanchard, P., Volk, R.J., Ringash, J., Peterson, S.K., Hutcheson, K.A. and Frank, S.J., 2016. Assessing 
head and neck cancer patient preferences and expectations: a systematic review. Oral oncology, 62, 
pp.44-53. 
 
Brady, G.C., Hardman, J.C., Paleri, V., Harrington, K.J. and Roe, J.W., 2020. Changing paradigms in the 
treatment of residual/recurrent head and neck cancer: implications for dysphagia 
management. Current opinion in otolaryngology & head and neck surgery, 28(3), pp.165-171. 
 
Burtness, B., Harrington, K.J., Greil, R., Soulières, D., Tahara, M., de Castro Jr, G., Psyrri, A., Basté, N., 
Neupane, P., Bratland, Å. and Fuereder, T., 2019. Pembrolizumab alone or with chemotherapy 
versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the 
head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. The Lancet, 394(10212), 
pp.1915-1928. 
 
Chen, A.Y., Frankowski, R., Bishop-Leone, J., Hebert, T., Leyk, S., Lewin, J. and Goepfert, H., 2001. The 
development and validation of a dysphagia-specific quality-of-life questionnaire for patients with 
head and neck cancer: the MD Anderson dysphagia inventory. Archives of Otolaryngology–Head & 
Neck Surgery, 127(7), pp.870-876. 
 
Chuang, S.C., Scelo, G., Tonita, J.M., Tamaro, S., Jonasson, J.G., Kliewer, E.V., Hemminki, K., 
Weiderpass, E., Pukkala, E., Tracey, E. and Friis, S., 2008. Risk of second primary cancer among 
patients with head and neck cancers: a pooled analysis of 13 cancer registries. International journal 
of cancer, 123(10), pp.2390-2396. 
 
Clarke, P., Radford, K., Coffey, M. and Stewart, M., 2016. Speech and swallow rehabilitation in head 
and neck cancer: United Kingdom National Multidisciplinary Guidelines. The Journal of Laryngology 
& Otology, 130(S2), pp.S176-S180 
 
Grünwald, V., Chirovsky, D., Cheung, W.Y., Bertolini, F., Ahn, M.J., Yang, M.H., Castro, G., Berrocal, 
A., Sjoquist, K., Kuyas, H. and Auclair, V., 2020. Global treatment patterns and outcomes among 
patients with recurrent and/or metastatic head and neck squamous cell carcinoma: Results of the 
GLANCE H&N study. Oral oncology, 102, p.104526. 
 
Iliffe S, Wilcock J, Drennan V, et al. Changing practice in dementia care in the community: developing 
and testing evidence-based interventions, from timely diagnosis to end of life (EVIDEM). 
Southampton (UK): NIHR Journals Library; 2015 Apr. (Programme Grants for Applied Research, No. 
3.3.) Appendix 65, Chapter 5: Five main stages in framework analysis. Available from: 
https://www.ncbi.nlm.nih.gov/books/NBK286110/ 
 
Jayaram, S.C., Muzaffar, S.J., Ahmed, I., Dhanda, J., Paleri, V. and Mehanna, H., 2016. Efficacy, 
outcomes, and complication rates of different surgical and nonsurgical treatment modalities for 

 
 
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recurrent/residual oropharyngeal carcinoma: a systematic review and meta‐analysis. Head & 
neck, 38(12), pp.1855-1861. 
 
Hamilton, D. and Paleri, V., 2017. Role of transoral robotic surgery in current head & neck 
practice. The Surgeon, 15(3), pp.147-154. 
 
Hardman, J., Liu, Z., Brady, G., Roe, J., Kerawala, C., Riva, F., Clarke, P., Kim, D., Bhide, S., Nutting, C. 
and Harrington, K., 2020. Transoral robotic surgery for recurrent cancers of the upper aerodigestive 
tract—Systematic review and meta‐analysis. Head & neck, 42(5), pp.1089-1104. 
 
Hutcheson, K.A., Barrow, M.P., Lisec, A., Barringer, D.A., Gries, K. and Lewin, J.S., 2016. What is a 
clinically relevant difference in MDADI scores between groups of head and neck cancer 
patients?. The Laryngoscope, 126(5), pp.1108-1113. 
 
List, M.A., Ritter‐Sterr, C. and Lansky, S.B., 1990. A performance status scale for head and neck 
cancer patients. Cancer, 66(3), pp.564-569. 
 
Louie, K.S., Mehanna, H. and Sasieni, P., 2015. Trends in head and neck cancers in England from 
1995 to 2011 and projections up to 2025. Oral oncology, 51(4), pp.341-348. 
 
Mandapathil, M., Roessler, M., Werner, J.A., Silver, C.E., Rinaldo, A. and Ferlito, A., 2014. Salvage 
surgery for head and neck squamous cell carcinoma. 
 
Mehanna, H., Kong, A. and Ahmed, S.K., 2016. Recurrent head and neck cancer: United Kingdom 
national multidisciplinary guidelines. The Journal of Laryngology & Otology, 130(S2), pp.S181-S190. 
 
NICE National Collaborating Centre for Cancer (UK) 2016. Cancer of the upper aerodigestive tract: 
assessment and management in people aged 16 and over. London: NICE.  
 
Paleri, V., Patterson, J., Rousseau, N., Moloney, E., Craig, D., Tzelis, D., Wilkinson, N., Franks, J., 
Hynes, A.M., Heaven, B. and Hamilton, D., 2018. Gastrostomy versus nasogastric tube feeding for 
chemoradiation patients with head and neck cancer: the TUBE pilot RCT 
 
Paleri, V., Hardman, J., Brady, G., George, A. and Kerawala, C., 2020. Transoral Robotic Surgery for 
Residual and Recurrent Oropharyngeal Cancers. Otolaryngologic Clinics of North America, 53(6), 
pp.1091-1108. 
 
Patterson, J.M., Brady, G.C. and Roe, J.W., 2016. Research into the prevention and rehabilitation of 
dysphagia in head and neck cancer: a UK perspective. Current opinion in otolaryngology & head and 
neck surgery, 24(3), pp.208-214. 
 
Patterson, J.M., Hildreth, A., McColl, E., Carding, P.N., Hamilton, D. and Wilson, J.A., 2011. The 
clinical application of the 100 mL water swallow test in head and neck cancer. Oral Oncology, 47(3), 
pp.180-184. 

 
 
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Roe, J.W., Drinnan, M.J., Carding, P.N., Harrington, K.J. and Nutting, C.M., 2014. Patient-reported 
outcomes following parotid-sparing intensity-modulated radiotherapy for head and neck cancer. 
How important is dysphagia?. Oral oncology, 50(12), pp.1182-1187. 
 
Rogers, S.N., Lowe, D., Brown, J.S. and Vaughan, E.D., 1999. The University of Washington head and 
neck cancer measure as a predictor of outcome following primary surgery for oral cancer. Head & 
Neck: Journal for the Sciences and Specialties of the Head and Neck, 21(5), pp.394-401. 
 
 
Schache, A.G., Powell, N.G., Cuschieri, K.S., Robinson, M., Leary, S., Mehanna, H., Rapozo, D., Long, 
A., Cubie, H., Junor, E. and Monaghan, H., 2016. HPV-related oropharynx cancer in the United 
Kingdom: an evolution in the understanding of disease etiology. Cancer research, 76(22), pp.6598-
6606. 
 
Sharp, H.M., List, M., MacCracken, E., Stenson, K., Stocking, C. and Siegler, M., 1999. Patients' 
priorities among treatment effects in head and neck cancer: Evaluation of a new assessment 
tool. Head & Neck: Journal for the Sciences and Specialties of the Head and Neck, 21(6), pp.538-546. 
 
Starmer, H.M., Arrese, L., Langmore, S., Ma, Y., Murray, J., Patterson, J., Pisegna, J., Roe, J., Tabor, L. 
and Hutcheson, K. (2021) Adaptation and Validation of the Dynamic Imaging Grade of Swallowing 
Toxicity for Flexible Endoscopic Evaluation of Swallowing: DIGEST™-FEES Journal of Speech, 
Language, and Hearing Research (IN PRESS) 
 
Steele, C.M., Namasivayam-MacDonald, A.M., Guida, B.T., Cichero, J.A., Duivestein, J., Hanson, B., 
Lam, P. and Riquelme, L.F., 2018. Creation and initial validation of the international dysphagia diet 
standardisation initiative functional diet scale. Archives of physical medicine and 
rehabilitation, 99(5), pp.934-944. 
 
White, H., Ford, S., Bush, B., Holsinger, F.C., Moore, E., Ghanem, T., Carroll, W., Rosenthal, E., 
Sweeny, L. and Magnuson, J.S., 2013. Salvage surgery for recurrent cancers of the oropharynx: 
comparing TORS with standard open surgical approaches. JAMA Otolaryngology–Head & Neck 
Surgery, 139(8), pp.773-777. 
 
Zafereo, M.E., Hanasono, M.M., Rosenthal, D.I., Sturgis, E.M., Lewin, J.S., Roberts, D.B. and Weber, 
R.S., 2009. The role of salvage surgery in patients with recurrent squamous cell carcinoma of the 
oropharynx. Cancer: Interdisciplinary International Journal of the American Cancer Society, 115(24), 
pp.5723-5733. 
 
 
 
 
 

 
 
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Appendix 1: Performance Status Scale in Head and Neck cancer 
standard operating procedure (SOP) 
Purpose: 
To describe the procedures employed when evaluating the Normalcy of Diet, Place of Eating and 
Understandibility of Speech scores using the Performance Status Scale for Head and Neck Cancer 
(PSS-HN). 
 
Scope: 
This SOP outlines the procedure to be carried out by the co investigator or trained Speech and 
Language Therapists (SLTs), performing the PSS-HN. 
 
Procedure: 
Timing of assessments 
The PSS-HN assessment is to be carried out at the time points as specified in the protocol: at 
baseline, and at 3, 6, and 12 following diagnosis. The PSS-HN assessment is to be carried out after 
completion of the patient reported outcomes, to avoid bias on self-reporting, but before the 
instrumental FEES assessment. 
 
Assessor  
The PSS-HN assessment should only be performed by appropriately trained staff including a member 
of the research team or trained SLT. 
 
Assessment  
It is anticipated that the PSS-HN assessment will take approx. 5 minutes to complete.  
Scores for the PSS-HN assessment are determined following an unstructured interview. The scores 
range from 0 to 100, with higher scores indicating better performance. There are separate scores for 
each of the 3 subscales. The subscales with the various food items and options can be found in the 
associated guidance document.  
Interviewer instructions for the three subscales are outlined below.  
 
Normalcy of diet  
It is recommended that the assessor begins by asking the patient what kinds of food they have been 
eating, and what foods have been difficult to eat. Based on the patient’s response, an item should be 
chosen at the low end of the scale.  
The assessor should move up the scale giving examples of foods in each category, asking the patient 
whether they are eating these foods. Even if a patient states they eat everything, enquiries should 
be made about specific items beginning with score 50 (soft chewable foods) and move upwards.  
The assessor should stop at an item at, and above, which the patient cannot eat. The patient 
receives the score below this item.  
If the patient eats a full diet, an enquiry should be made if the patient needs to drink more liquids 
than usual with meals. Eating a full diet with intake of extra fluids is scored 90.  

 
 
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If the patient can take foods orally, but is also using a feeding tube, the score should be based on 
solid foods and indicate that a feeding tube is used.  
 
Public eating  
The patient should be asked:  
• 
where they eat – in a restaurant, at home, at friends/relatives’ homes, etc.  
• 
with whom they eat – always alone, with family/friends, etc.  
• 
if they choose different foods when eating with others – softer, less messy, etc.  
• 
when was the last time they ate in a restaurant, MacDonald’s, picnic, family reunion.  
The score beside the description that best fits the patient should be chosen. A patient on a restricted 
diet (e.g. tube feeding, pureed foods) who does not eat in public but will join others in a public 
eating setting should be scored 75. Inpatients should receive a score of 999.  
 
Understandability of speech  
This score is based on the interviewer’s ability to understand the patient during conversation (in this 
case, based on conversation about normalcy of diet and public eating). The score beside the 
description that best fits the patient should be chosen. The assessor should assess the clarity of 
speech when not directly facing the patient, or whether face-to-face contact is required to 
understand them.   
 
Normalcy of Diet 
Eating in public 
Speech intelligibility 
100 Full diet with no 
restrictions 
90 Full diet with liquid 
assistance 
80 All meats 
70 Carrots, celery (crunchy) 
60 Dry bread & crackers 
50 Soft, chewable foods 
(pasta, canned soft fruits, fish) 
40 Soft foods requiring no 
chewing e.g. mashed potato, 
apple sauce 
30 Puree 
20 Warm liquids 
10 Cold liquids 
0 Non oral 
100 No restriction of place, 
food or companion (eats out at 
any opportunity) 
75 No restriction of place, but 
restricts diet when in public 
(eats anywhere, but may limit 
intake to less "messy" foods 
(e.g., liquids) 
50 Eats only in presence of 
selected persons in selected 
places 
25 Eats only at home in 
presence of selected persons 
0 Always eats alone 
 
100 Always understandable 
75 Understandable most of 
the time; occasional repetition 
necessary 
50 Usually understandable; 
face-to-face 
25 Never understandable; may 
use written 
0 No communication 
 
 
CRF completion  
The PSS-HN assessment CRF should be completed as soon as possible after completion of the 
assessment.  

 
 
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Appendix 2: IDDSI Functional Diet Score: SOP 
Purpose: 
To describe the procedures employed when evaluating the IDDSI functional diet score 
 
Scope: 
This SOP outlines the procedure to be carried out by the co investigator or trained Speech and 
Language Therapists (SLTs), when assigning the IDDSI functional diet score. 
 
Procedure: 
Timing of assessments 
The IDDSI functional diet score is to be carried out at the time points as specified in the protocol: at 
baseline, and at 3, 6, and 12 following diagnosis.  
 
Assessor  
The IDDSI functional diet score assessment should only be performed by appropriately trained staff 
a member of the research team or trained SLT. 
 
Assessment  
It is anticipated that the IDDSI functional diet assessment will take approx. 2 minutes to complete.  
Scores for the IDDSI functional score are determined following an unstructured interview regarding 
the food and drinks currently being managed by the patient. The scores range from 0 to 8 with 
higher scores indicating better function.  
 
The IDDSI Functional Diet Scale score corresponds to the number in the intersecting cell of the 
column showing the food level and the row showing the drink level recommended for the patient. 
An IDDSI Functional Diet Scale score of 0 applies for recommendations of nothing by mouth (NPO), 
with exclusive nonoral feeding. 
 

 
 
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Appendix 3: 100ml Water Swallow Test (100ml WST) SOP 
Purpose: 
To describe the procedures employed when evaluating swallowing using the 100ml WST.  
 
Scope: 
This SOP outlines the procedure to be carried out by the co investigator or trained Speech and 
Language Therapists (SLTs), performing the100ml WST. 
 
Procedure: 
Timing of assessments 
The 100ml WST is to be carried out at the time points as specified in the protocol: at baseline, and at 
3, 6, and 12 following diagnosis.  
 
Assessor  
The 100ml WST should only be performed by a member of the research team or trained SLT 
 
Assessment  
It is anticipated that the 100ml WST assessment will take approx. 2 minutes to complete.  
Patient should be alert, in an upright, comfortable position. If possible, the patient should be 
allowed to rest for a few minutes after arrival to gain composure.   
If a patient is already using a head posture on fluids to eliminate aspiration/ penetration the WST 
should still be performed. This does not mean an immediate fail.  
If patients are anxious about doing the test, a tester cup can be given to patients to reduce anxiety 
prior to the actual test. The tester cup can also be used to help patients clear any secretions from 
the throat before the WST is performed.  
Whether a tester cup is appropriate is left to the clinical judgement of the treating SLT or the 
individual delegated to perform the WST.  
It should also be re-emphasised that patients can take as much time as they need and they may stop 
the test at any time if they feel uncomfortable  
 
The following is needed to perform the WST:  
• 
Stopwatch  
 
• 
Plastic cup  
• 
Syringe or measuring cup  
 
• 
Tap water  
 
Face-to-face assessment: 
The assessor measures 100mL of water (neither warm, nor chilled) in a plastic cup using the syringe 
or measuring cup.  
The patient is asked to drink all the water “as quickly as possible, without making themselves 
uncomfortable”, and without trying to talk during the assessment.  

 
 
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The assessor simultaneously places their fingers gently on the patient’s thyroid cartilage to measure 
the number of swallows. Timing starts when the water touches the patient’s bottom lip and stops on 
the last swallow (including any breaks that might be required between swallows), including any final 
clearance swallow.  
The WST should not be performed if individuals have been recommended by their managing 
clinician to remain nil by mouth.   
If there are overt signs of significant aspiration (explosive coughing, prolonged coughing) or the 
patient is becoming distressed, the assessment and timing is stopped immediately and the 
remaining amount of water measured and recorded.   
It is acceptable if patients cannot finish the test – inability to complete the test is an important result 
and should be reported on the CRF by recording how much water the patient swallowed.  
It is recommended that patients who are unable to complete the WST should be highlighted to SLTs 
for further review as per standard care.  
 
Remote assessment  
Ahead of the assessment, ask the patient to measure 100ml of water into a clear glass.  
Set the video-conferencing up, so that the patient is in full view of the camera.  
Explain that you are going to time them drinking the water and count the number of swallows taken. 
Demonstrate to them a lateral head position with shoulders turned (but not their neck) for the task 
to enable viewing. Demonstrate the position of their hand holding the glass, ensuring it is on the 
opposite side to the video camera to give the assessor a full view.   
Give the following instructions to the patient: ‘I would like you to drink all of the water as quickly 
and as comfortably as possible for you. I am going to count the number of swallows and time it takes 
for you to finish the water. Please start when you are ready. `  
Using the stopwatch, the assessor times the swallow test from when the water reaches the patient’s 
lips, to when all the water has been swallowed and there is no water remaining in the glass. The 
assessor simultaneously counts the number of swallows taken to swallow 100ml, by observing the 
upward movement of the Adam’s Apple (one elevation equals one swallow). The assessor records 
the time taken and number of swallows to complete the water swallow test. 
 
Recording and Reporting 
The assessor records:  
• 
The number of swallows taken  
• 
The time taken to complete the task (in seconds; round to nearest second)  
• 
The amount of water the patient swallowed  
• 
The presence/absence of any signs of aspiration/ penetration (throat clear/ cough/ wet 
voice) during or after the task.  
 
In the database input swallow volume (mls swallowed / number of swallows) swallow capacity (mls 
swallowed / time taken in seconds) 
CRF completion  
 

 
 
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The 100ml WST assessment CRF should be completed as soon as possible after completion of the 
assessment.  

 
 
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Appendix 4: Dynamic Imaging Grade of Swallowing Toxicity for 
Fibreoptic Endoscopic Evaluation of Swallowing (FEES-DIGEST) SOP 
Purpose: 
To describe the procedures employed when evaluating swallowing toxicity using the FEES_ DIGEST 
grading system.  
 
Scope: 
This SOP outlines the procedure to be carried out by the co investigator or trained Speech and 
Language Therapists (SLTs) when grading the FEES- DIGEST. 
 
Procedure: 
Timing of assessments 
The FEES_DIGEST is to be carried out at the time points as specified in the protocol: at baseline, and 
at 3, 6, and 12 following diagnosis.  
 
Assessor  
The FEES-DIGEST assessment should only be performed by a member of the research team or 
appropriately trained SLT. 
 
Assessment  
It is anticipated that the FEES-DIGEST will take approx. 20 minutes to complete.  
The Fibreoptic Endsocopic Evaluation of Swallowing is carried out as per the guidelines in the Royal 
Marsden Fibreoptic Endoscopic Evaluation of Swallowing (FEES) policy 1762.  
 
CRF completion  
The FEES DIGEST CRF should be completed as soon as possible after completion of the assessment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Appendix 5: Protocol Version History 
 
Version 
Date 
Reason for Change 
V2.0 
12.04.2022 
Protocol updated to facilitate remote consent from 
participants both during the COVID-19 pandemic and until end 
of study recruitment.  
V3.0 
19.12.2022 
Minor update to protocol wording to describe the patient 
population, no changes made to the eligibility criteria 
Named study statistician removed as not applicable 
V4.0 
09.02.2023 
Addition of retrospective patient cohort for Part B of the study 
and appropriate adjustment to the sample size for the study 
V5.0 
28.02.2023 
Addition of PIC sites as a recruitment strategy  
V5.1  
22.05.2024 
End point data to be collected to 6 months only.  
Removal of adverse event reporting requirements.