RECUT PLUS: Exploratory Study of Clonal Evolution in Cancer for Patients Undergoing Transoral Robotic Surgery for Radiation Exposed Residual/reCurrent Tumours of the Upper Aerodigestive Tract
Conditions: Head and Neck Cancer
Sponsor: Royal Marsden NHS Foundation Trust

THE RECUT PLUS STUDY 
 
Exploratory study of clonal evolution in cancer for 
patients undergoing transoral Robotic surgery for 
radiation Exposed residual/reCurrent tumours of the 
Upper aerodigestive Tract. 
 
Protocol version: 
1.1 
Date: 
18th March 2020 
 
 
Sponsor: 
The Royal Marsden NHS foundation Trust 
 
Fulham Road, London SW3 6JJ 
 
 
CCR number: 
5263 
IRAS number: 
280262 
 
 
Chief Investigator: 
Professor Vinidh Paleri 
Consultant Head & Neck and Thyroid Surgeon, 
   The Royal Marsden Hospital, London 
Professor of Robotic & Endoscopic Head & Neck Surgery, 
   The Institute of Cancer Research, London 
 
 
Clinical Research  
Fellow: 
Mr John Hardman 
Specialty Registrar in Otorhinolaryngology, 
   The Institute of Cancer Research, London 
   The Royal Marsden Hospital, London 
 
 
Molecular analysis 
lead: 
Dr Ben O’Leary 
NIHR Clinical Lecturer 
   The Institute of Cancer Research, London 
   The Royal Marsden Hospital, London 
 
 
Molecular analysis 
supervisor: 
Professor Kevin Harrington 
Consultant Clinical Oncologist, 
   The Royal Marsden Hospital, London 
Professor of Biological Cancer Therapies, 
   The Institute of Cancer Research, London 
 
 
Contact: 
vinidh.paleri@rmh.nhs.uk 
johncharles.hardman@nhs.net  
 
 
 

The RECUT Plus Study protocol v1.1 
18th March 2020 
IRAS: 280262 
CCR: 5263 
Page 2 
Table of Contents 
 
1 
Version history ........................................................................................................... 3 
2 
Project summary ........................................................................................................ 4 
3 
Funding ...................................................................................................................... 5 
4 
Signature Page ........................................................................................................... 6 
5 
Rationale and background information ..................................................................... 7 
6 
Study goal and objectives .......................................................................................... 8 
7 
Study design and setting ............................................................................................ 9 
8 
Participant Eligibility Criteria .................................................................................... 10 
9 
Study procedures and methodology ........................................................................ 11 
10 Statistics and Data Analysis ...................................................................................... 15 
11 Data Management ................................................................................................... 16 
12 Ethical Considerations .............................................................................................. 17 
13 Dissemination policy ................................................................................................ 18 
14 Key study contacts ................................................................................................... 19 
15 Table of acronyms .................................................................................................... 20 
16 References ............................................................................................................... 21 
 

The RECUT Plus Study protocol v1.1 
18th March 2020 
IRAS: 280262 
CCR: 5263 
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1  VERSION HISTORY 
 
Protocol 
version no. 
Date 
Version 
1.0 
2020/02/12 
Prepared for submission to the Committee for 
Clinical Research 
1.1 
2020/03/18 
Following CCR feedback 
 
 
 
 
 
 
 
 
 
 
 
 

The RECUT Plus Study protocol v1.1 
18th March 2020 
IRAS: 280262 
CCR: 5263 
Page 4 
2 PROJECT SUMMARY 
Study Title 
Exploratory study of clonal evolution in cancer for patients 
undergoing transoral Robotic surgery for radiation Exposed 
residual/reCurrent tumours of the Upper aerodigestive Tract. 
Short Title 
The RECUT Plus Study  
Study Design 
RECUT Plus is an exploratory molecular analysis study to assess 
the selective impact of radiation therapy on H&N SCC. 
Study Participants 
Patients undergoing transoral robotic surgery for radiation 
exposed residual/recurrent/new primary tumours of the upper 
aerodigestive tract. 
Planned Sample 
Size 
Up to 20 participants. 
Follow Up Duration 
Up to 5 years clinical follow up for oncological outcomes.  
Planned Trial 
Period 
Prospective identification of patients will take place over 12 
months. 
Primary objective 
Assess the molecular makeup of head and neck tumours that 
have not responded to radiotherapy treatment, or which recur 
having previously responded.  
Secondary 
objectives 
1. Compare the sub clonal architecture of HNSCC before and after 
radiotherapy. 
2. Compare mutational signatures between the primary disease and 
resistant sub clones. 
3. Assess resistant sub clones for loss of heterozygosity (LOH) at the 
HLA loci. 
4. Report the oncological status of cases at 5 years. 
Methods 
• 
This is an exploratory molecular analysis study. 
• 
Retrospective and prospective participants will be identified from 
screening historic and future H&N MDT lists at RMH. 
• 
Following informed consent, germline DNA data will be obtained 
from blood, saliva or buccal swabs. This will be compared to biopsy 
samples from the original primary cancer and microdissected 
samples from the radiation exposed residual/recurrent/new 
primary cancer removed using transoral robotic surgery. 
• 
DNA will be extracted and used to create exome libraries.  
• 
Variant calls and copy number will be used to infer the clonal 
architecture at each sampled site within the resected specimen.  
• 
The presence or absence of sub clones before treatment and after 
treatment will be compared and their mutation and copy number 
profile changes analysed. 
• 
Mutational signatures in resistant sub clones will be inferred and 
assessed to see if they differ between each other and from the 
dominant processes driving evolution in primary disease  
• 
The resistant sub clones will also be assessed for loss of 
heterozygosity (LOH) at the HLA loci.  
• 
Hospital records and/or GP records will be used to record 
incidence of recurrence and survival for up to 5 years following 
surgery.  

The RECUT Plus Study protocol v1.1 
18th March 2020 
IRAS: 280262 
CCR: 5263 
Page 5 
3 FUNDING 
Funder 
Financial and Non-financial support given 
 
BRC Uncommon Cancer theme 
 
 
Awarded £20,015 on 07 April 2020 (ref: B089) 
 
Oracle Cancer Trust 
 
 
Application for £100,000 in progress 

The RECUT Plus Study protocol v1.1 
18th March 2020 
IRAS: 280262 
CCR: 5263 
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4 SIGNATURE PAGE 
The undersigned confirm that the following protocol has been agreed and accepted and that the Chief 
Investigator agrees to conduct the study in compliance with the approved protocol and will adhere to the 
principles outlined in the Declaration of Helsinki, the Sponsor’s SOPs, and other regulatory requirement. 
I agree to ensure that the confidential information contained in this document will not be used for any 
other purpose other than the evaluation or conduct of the investigation without the prior written consent 
of the Sponsor 
I also confirm that I will make the findings of the study publicly available through publication or other 
dissemination tools without any unnecessary delay and that an honest accurate and transparent account 
of the study will be given; and that any discrepancies from the study as planned in this protocol will be 
explained. 
 
For and on behalf of the Study Sponsor: 
 
 
Print 
Name: 
 
 
 
Signature
:  
  
 
 
Date:  
 
 
Chief Investigator: 
 
 
Print 
Name: 
Vinidh Paleri 
 
 
Signature
:  
  
 
 
Date:  
 
 
 

The RECUT Plus Study protocol v1.1 
18th March 2020 
IRAS: 280262 
CCR: 5263 
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5 RATIONALE AND BACKGROUND INFORMATION 
Radical radiotherapy for head and neck squamous cell cancer (HNSCC) can be curative, but when relapse 
does occur it is often within the radiotherapy-treated area.[1] It is unknown whether HNSCC cancer relapse 
after curative radiotherapy reflects primary resistance or evolution of resistance on treatment. 
Understanding this could open new avenues for improving the efficacy of radical radiotherapy and tailor 
the systemic treatments given after tumour relapse. 
The Cancer Genome Atlas has begun to shed light on the genomic landscape of head and neck cancer[2] but 
little work has been done to investigate the impact of molecular characteristics on treatment with 
radiotherapy. Intra-tumoural heterogeneity has been demonstrated in a number of malignancies, with an 
early analysis of the head and neck TCGA data[2] suggesting higher levels of intra-tumoural heterogeneity 
may associate with poorer clinical outcome.[3] This invites the hypothesis that pre-existing sub clonal 
diversity may drive radiotherapy resistance. 
Although many patients with head and neck cancer can be offered potentially curative treatment, we do 
not understand why some people are cured and others are not. There has been an explosion in genomics 
research in many cancers, but this remains an understudied area in head and neck cancer. There are 
currently no treatments available to patients with head and neck cancer based on genomic insights. This 
study begins to address the unmet need of patients who are failed by radical treatment and provides a 
starting point for more detailed investigations into the relationships between cancer genomics and clinical 
outcomes. 

The RECUT Plus Study protocol v1.1 
18th March 2020 
IRAS: 280262 
CCR: 5263 
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6 STUDY GOAL AND OBJECTIVES 
6.1 
Goal 
To establish the clonal architecture and evolution of H&N cancers occurring in previously irradiated fields. 
6.2 
Primary objective 
Assess the molecular makeup of head and neck tumours that have not responded to radiotherapy 
treatment, or which recur having previously responded.  
6.3 
Secondary objectives 
1. 
Compare the sub clonal architecture of HNSCC before and after radiotherapy. 
2. 
Compare mutational signatures between the primary disease and resistant sub clones. 
3. 
Assess resistant sub clones for loss of heterozygosity (LOH) at the HLA loci. 
4. 
Report the oncological status of cases at 5 years. 

The RECUT Plus Study protocol v1.1 
18th March 2020 
IRAS: 280262 
CCR: 5263 
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7 STUDY DESIGN AND SETTING 
7.1 
Study design 
RECUT Plus is an exploratory molecular analysis study to assess the selective impact of radiation therapy 
on HNSCC.  
7.2 
Study setting 
Participants will be recruited from the Royal Marsden Hospital (RMH), Chelsea, a tertiary referral H&N 
cancer unit in London, UK, specialising in transoral robotic surgery.  

The RECUT Plus Study protocol v1.1 
18th March 2020 
IRAS: 280262 
CCR: 5263 
Page 10 
8 PARTICIPANT ELIGIBILITY CRITERIA 
8.1 
Inclusion criteria 
• 
Aged over 18 
• 
Previous H&N cancer treated with radiotherapy. 
• 
Undergoing TORS as part of their management for residual, recurrent or new primary H&N cancer. 
8.2 
Exclusion criteria 
• 
Where TORS is used in a diagnostic setting only 
• 
Nasopharyngeal and thyroid head and neck cancers 
• 
Where no tissue specimens are available from the recurrent/residual/secondary tumour for the 
retrospective cohort 

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18th March 2020 
IRAS: 280262 
CCR: 5263 
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9 STUDY PROCEDURES AND METHODOLOGY 
9.1 
Population 
Patients undergoing transoral robotic surgery for radiation exposed residual/recurrent/new primary 
tumours of the upper aerodigestive tract. 
9.2 
Patient identification 
For prospective participants, the RECUT Plus study team will screen the weekly H&N MDT meetings at the 
Royal Marsden Hospital (RMH). 
For retrospective participants, the RECUT Plus study team will screen previous MDT lists for consecutive 
patients treated with transoral robotic surgery since the programme was established at RMH in September 
2017. 
9.3 
Sampling timeframe 
No limitation will be placed on the recruitment window. See procedures.  
9.4 
Consent 
9.4.1.1 
Prospective 
Prospective participants will be informed of the RECUT Plus study by a member of their usual care team at 
RMH during their routine outpatient appointments for follow up of their H&N cancer. Participants will be 
provided with the Participant Information Sheet and copy of the Informed Consent Form. If they express 
interest in taking part, then consent will be obtained by a member of the RECUT Plus team, or an 
appropriately trained delegate, detailed in the Delegation Log.  
9.4.1.2 
Retrospective 
Where patients have returned to their referring institution and are no longer under active regular follow 
up at RMH, the patient’s GP will be contacted in order to obtain the patient’s status. If the patient is alive 
and well, a research pack will be sent to the patient via post and email. This pack will contain the Cover 
Letter, the Participant Information Sheet and the Informed Consent Form. It will also contain a saliva 
collection tube and buccal swab. If there has been no response after 3 weeks, a second pack will be sent 
out to allow for postal losses. If there has been no response after a further 3 weeks, a final attempt to 
contact the patient will be made via telephone. 
9.5 
Follow up 
The electronic patient record will be used to follow up patients for up to 5 years from the date of their 
robotic surgery. Where patients are no longer under active regular follow up at RMH, we will contact their 
GP to ask about disease recurrence and survival.  
9.6 
Pseudonymisation 

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18th March 2020 
IRAS: 280262 
CCR: 5263 
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9.6.1.1 
Clinical data 
We will be collecting identifiable data as part of the RECUT Plus study. This information will be held by the 
study sponsor on an excel spread sheet  stored on a Trust computer in line with local data governance 
policies.  
9.6.1.2 
Molecular data 
Tissue specimens will be identified only using the RECUT Plus Study ID. As such, no patient identifiable data 
will be processed outside of RMH or by the ICR laboratories.  
9.7 
Dataset  
9.7.1.1 
Clinical data 
The full dataset is available in an associated Excel Data Tool (combined eCRF and database). The dataset is 
divided into the following areas: 
1. General patient details: Demographics, smoking/alcohol and co-morbidities 
2. First cancer: Involved sites, staging, procedures and adjuvant treatment 
3. TORS for recurrence: Involved sites, staging, procedures, complications and adjuvant treatment 
4. Post-operative histology: Staging and margins 
5. Outcome: Survival, recurrence, follow-up 
9.7.2 
Co-morbidities 
The co-morbidity score will be taken using the Adult Co-morbidity Evaluation-27 (ACE-27) index, which is 
validated for use in H&N cancer patients[4,5]. This rates the grade of decompensation affecting the various 
body systems, as well as presence of obesity and the status of any cancer or substance abuse. The grade 
of decompensation ranges between none (Grade 0) through mild, moderate and severe decompensation 
(Grades 1 to 3). The result is an Overall Comorbidity Score of 0 to 3, taken as the highest grade of 
decompensation in any one system/category, unless the patient scores grade 2 in two more different 
systems/categories, in which case they are designated Overall Score 3.  
9.7.3 
Classification of ‘recurrent’ disease 
The following timeframes will be used to classify tumours treated after management of the original 
primary: 
<12 months:  
 
Residual disease 
12 months, <5 years:  
Recurrent disease 
<5 years: 
 
New primary disease, separate site 
5 years  
 
New primary disease 
9.8 
Specimens 

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18th March 2020 
IRAS: 280262 
CCR: 5263 
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9.8.1 
Germline and circulating DNA samples 
Patients will be asked to provide blood, saliva and/or buccal swabs. This will be used to perform germline 
DNA analysis. Prospectively recruited participants will be asked to provide samples pre and post operatively 
within a 2-week timeframe of their date of surgery. Retrospectively recruited participants will be able to 
provide a pre-operative sample but will be asked to provide a sample at the time of recruitment.  
9.8.2 
Tumour samples 
All tumour specimens in this study will have been taken as part of standard care. No additional biopsies or 
specimens will be taken for the purpose of this study. Molecular analysis will be performed on the biopsy 
specimens from the original presentation of the cancer and on the resected cancer which had occurred in 
the irradiated field. Fresh frozen and formalin fixed paraffin embedded samples will be collected after the 
tumour has been resected for the prospective participants and formalin fixed paraffin embedded 
specimens alone will be analysed for the retrospective participants.   
9.8.3 
Storage, labelling and postage of blood, saliva, buccal swab and tissue samples  
All RECUT Plus blood, saliva and buccal swab samples and tissue samples should be collected, labelled, 
stored and shipped as detailed in the RECUT Plus  Sample Collection Guidelines.  
All samples must be labelled with the patient’s study identifier (patient Registration Number), date of birth 
and date of sample to enable cross-referencing.  
All samples should be posted to the central laboratory at the Institute of Cancer Research in the packaging 
provided.  
9.8.4 
Tissue Blocks  
Archival blocks will be collected in batches. ICR will notify the sites when block collection is required. All 
samples should be sent by post to the following address:  
Dr Ben O’Leary 
2S8 
Chester Beatty Labs 
The Institute of Cancer Research  
237 Fulham Road, London SW3 6JB 
9.9 
Withdrawal criteria 
Patients may withdrawal from the study at any time at their own request, or they may be discontinued at 
the discretion of the Principal Investigator. This can occur for the following reason: 
Patient decision  
Lost to follow-up 
Death 
Pregnancy 
Protocol violation  
Ineligibility  
Patient noncompliance  
PI decision  
If the patient is withdrawn from the study the primary reason as well as the date of withdrawal will be 
recorded in the in the Excel Data Tool (combined eCRF and database). Should a patient withdraw consent 

The RECUT Plus Study protocol v1.1 
18th March 2020 
IRAS: 280262 
CCR: 5263 
Page 14 
for their samples to be used in RECUT Plus their blood, saliva and buccal swabs samples will be destroyed 
and tissue samples returned to the site for archiving. Data collected at the point of withdrawal will continue 
to be used by the study team.  

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18th March 2020 
IRAS: 280262 
CCR: 5263 
Page 15 
10 STATISTICS AND DATA ANALYSIS 
10.1 Sample size 
This is an exploratory study and as such will not be powered prospectively. Funding for consumables will 
limit the RECUT Plus sub-study to up to 20 patients initially 
10.2 Study duration 
The study will continue until up to 20 patients have been recruited. 
10.3 Statistical analysis methods 
10.3.1 Clinical data analysis 
Descriptive analysis only. No statistical analysis of the clinical data will be performed in this exploratory 
study. 
10.3.2 Molecular data analysis 
Detailed description of the molecular analysis methodology is beyond the scope of this protocol.  

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18th March 2020 
IRAS: 280262 
CCR: 5263 
Page 16 
11 DATA MANAGEMENT 
11.1 Data collection tools and source document identification 
11.1.1 Source documents 
The electronic patient record will form the principal source for clinical data. Data may also be entered 
directly onto the Excel Data Tool (combined eCRF and database) form where this information would not be 
collected as part of standard care.  As such the Excel Data Tool (combined eCRF and database) may be a 
source document also. 
11.1.2 Excel Data Tool (combined eCRF and database) 
Clinical data will be collected directly onto the Excel Data Tool (combined eCRF and database). This will be 
stored in the electronic site file on the shared drive for clinical studies conducted by the H&N surgery 
research team. In accordance with local data governance regulations for patient identifiable data.  
11.2 Data handling and record keeping 
The Excel Data Tool (combined eCRF and database)will be held in a folder on computers of the Royal 
Marsden Hospital NHS Foundation Trust and held for 5 years. This folder will have a security system to 
protect against unauthorized access. Each update of the data will be recorded and saved as a separate 
version in the folder so there will be no deletion of the entered data.  Each participant will have their own 
trust medical record number (MRN) and a study ID allow identification of all the data reported for each 
participant and for pseudonymisation for the molecular analysis. 
Professor Vinidh Paleri, the Chief Investigator, will be the custodian of the data submitted to the Royal 
Marsden Hospital.  
The chief investigator and the Royal Marsden Hospital NHS Foundation Trust will keep records of all 
participating patients and all original signed informed consent forms. 
Data storage and management for the molecular analysis will be at the Institute of Cancer Research, 
London. Data will be pseudonymised with the study ID, encrypted and held in line with local data 
governance protocols.  
11.3 Access to data 
Direct access will be granted to authorised representatives from the Sponsor and the regulatory authorities 
to permit study-related monitoring, audits and inspections, in line with participant consent.  
11.4 Archiving 
All study documents will be archived by the Royal Marsden Hospital NHS Foundation Trust following 
submission of the end of study report.  The site file and essential documents, including the CRFs, will be 
archived for 12 months after completion of the study.  These documents will be stored in a location 
determined by the Sponsor in line with their standard operating procedures.  Any destruction of essential 
documents will require authorisation from the Royal Marsden Hospital NHS Foundation Trust. 

The RECUT Plus Study protocol v1.1 
18th March 2020 
IRAS: 280262 
CCR: 5263 
Page 17 
12 ETHICAL CONSIDERATIONS 
The protocol will be submitted for ethical review to the  Health Research Authority’s ‘Integrated Research 
Application System’ (IRAS).  
The RECUT Plus Study is sponsored by The Royal Marsden NHS Foundation Trust and has been approved 
by the Sponsor’s Committee for Clinical Research (CCR). The Royal Marsden NHS Foundation Trust will 
ensure that the study has received ethics approval from a research ethics committee (REC) and has received 
Health Research Authority (HRA) approval.  
12.1 Trial Management Group  
A Trial Management Group (TMG) will be set up and membership will include Chief Investigator, Co-
Investigators and Senior Trial Manager. Principal Investigators and other key study personnel will be invited 
to join the TMG as appropriate. The TMG has operational responsibility for the conduct of the trial. The 
TMG is responsible for monitoring recruitment, safety and governance of the trial as well as collaborating 
with subsequent translational sub-studies. The TMG will also review any safety concerns and can convene 
a meeting if significant concerns exist. 

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18th March 2020 
IRAS: 280262 
CCR: 5263 
Page 18 
13 DISSEMINATION POLICY 
Data arising from the study are owned by the Sponsor.  Findings will be submitted for publication in relevant 
H&N or Cancer peer reviewed journals.  Funders will be acknowledged in any subsequent reports.  
Authorship will be granted in line with criteria defined by The International Committee of Medical Journal 
Editors.  
 

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18th March 2020 
IRAS: 280262 
CCR: 5263 
Page 19 
14 KEY STUDY CONTACTS 
Name 
Vinidh Paleri 
Role(s) 
Chief investigator 
Primary academic supervisor to John Hardman 
Responsibilities 
Including, not limited to: 
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. 
Analysis and write up. 
 
Name 
Kevin Harrington 
Role(s) 
Molecular analysis supervisor 
Backup academic supervisor to John Hardman 
Responsibilities 
Including, not limited to: 
Oversight of project design, conduct and reporting.  
Analysis and write up. 
 
Name 
John Hardman 
Role(s) 
Co-investigator 
Clinical research fellow 
Responsibilities 
Including, not limited to: 
Recruitment of patients.  
Coordination of data governance and control of the Excel Data 
Tool (combined eCRF and database).  
Analysis and write up. 
 
Name 
Ben O’Leary 
Role(s) 
Molecular analysis lead 
Associate academic supervisor to John Hardman 
Responsibilities 
Including, not limited to: 
Project design.  
Recruitment of patients.  
Molecular analysis.  
Analysis and write up. 
 
This study will contribute towards the pursuit of an MD(Res) at the Institute for Cancer Research by John 
Hardman, the Clinical Research Fellow. Some of the data collected from this study may be used in the 
relevant thesis, prior to ultimate submission for publication or presentation.  

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18th March 2020 
IRAS: 280262 
CCR: 5263 
Page 20 
15 TABLE OF ACRONYMS 
Acronym 
Meaning 
ACE-27 
Adult Co-morbidity Evaluation-27 
ASA 
American Society of Anesthesiologists 
CCR 
Committee for Clinical Research (Royal Marsden Hospital) 
CT 
Computed tomography 
eCRF 
Electronic case report form 
H&N 
Head and neck 
HLA 
Human Leukocyte Antigen 
HNSCC 
Head and neck squamous cell carcinoma 
HPV 
Human papilloma virus 
HRA 
Health Research Authority 
IRAS 
Integrated Research Application System 
KM 
Kaplan Meier 
LOC 
Loss of heterozygosity 
MDADI 
M. D. Anderson Dysphagia Inventory 
MDT 
Multidisciplinary team 
MRI 
Magnetic resonance imaging 
PET CT 
Positron emission tomography and computed tomography 
PSS-HN 
Performance status scale for head and neck cancer patients 
RMH 
Royal Marsden Hospital 
SCC 
Squamous cell carcinoma 
TORS 
Transoral robotic surgery 
 

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18th March 2020 
IRAS: 280262 
CCR: 5263 
Page 21 
16 REFERENCES 
1.  Mehanna H, Kong A, Ahmed S. Recurrent head and neck cancer: United Kingdom National 
Multidisciplinary Guidelines. The Journal of Laryngology & Otology 2016;130(S2):S181–90.  
2.  Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 
2015;517(7536):576–82.  
3.  Mroz EA, Tward AM, Hammon RJ, Ren Y, Rocco JW. Intra-tumor Genetic Heterogeneity and Mortality 
in Head and Neck Cancer: Analysis of Data from The Cancer Genome Atlas. PLOS Medicine 
2015;12(2):e1001786.  
4.  Piccirillo JF. Importance of comorbidity in head and neck cancer. Laryngoscope 2000;110(4):593–
602.  
5.  Paleri V, Wight RG. Applicability of the adult comorbidity evaluation - 27 and the Charlson indexes to 
assess comorbidity by notes extraction in a cohort of United Kingdom patients with head and neck 
cancer: a retrospective study. J Laryngol Otol 2002;116(3):200–5.