Management of head and neck cancers (PDF , 603kb)

Management of head and neck cancers

Bulletin on the effectiveness of health service interventionsfor decision makers

Bulletin on the effectiveness of health service interventionsfor decision makers

CENTRE FOR REVIEWS AND DISSEMINATION

VOLUME 8 NUMBER 5 2004 ISSN: 0965-0288

■ Over the next few years,assessment and treatmentservices for patients with headand neck cancers will becomeincreasingly concentrated incancer centres servingpopulations of over a million.

■ Multidisciplinary teams(MDTs) will be central to theservice, each managing at least100 new cases of upperaerodigestive tract cancer perannum. They will beresponsible for assessment,treatment planning andmanagement of every patient.Specialised teams will dealwith patients with thyroidcancer, and with those withrare or particularly challengingconditions such as salivarygland and skull base tumours.

■ Arrangements for referral ateach stage of the patient’scancer journey should bestreamlined. Diagnostic clinicsshould be established forpatients with neck lumps.

■ A wide range of supportservices should be provided.Clinical nurse specialists,speech and languagetherapists, dietitians and

restorative dentists play crucialroles but a variety of othertherapists are also required,from the pre-treatmentassessment period untilrehabilitation is complete.

■ Co-ordinated Local SupportTeams should be establishedto provide long-term supportand rehabilitation for patientsin the community. Theseteams will work closely withevery level of the service, fromprimary care teams to thespecialist MDT.

■ MDTs should takeresponsibility for ensuring thataccurate and complete data ondisease stage, managementand outcomes are recorded.Information collection andaudit are crucial to improvingservices and must beadequately supported.

■ Research into the effectivenessof management – includingassessment, treatment,delivery of services andrehabilitation – urgentlyrequires development andexpansion. Multi-centreclinical trials should beencouraged and supported.

This bulletin summarisesthe research evidencethat informed theguidance ‘ImprovingOutcomes in Head andNeck Cancers’

EffectiveHealth Care

VOLUME 8 NUMBER 5 20042 EFFECTIVE HEALTH CARE Management of head and neck cancers

A. BackgroundA.1. Incidence and mortalityThere are over 30 specific sites inthe head and neck cancers group.Cancer of each particular site isrelatively uncommon (Tables 1and 2), however the group as awhole accounts for over 8,000cases and 2,700 deaths per year inEngland and Wales.The majority of these cancers arisefrom the surface layers of theupper aerodigestive tract (UAT):the mouth, lip and tongue (oralcavity), the upper part of thethroat and respiratory system(pharynx), and the voice-box(larynx). Other UAT sites includethe salivary glands, nose, sinusesand middle ear, but these cancersare relatively rare; cancers thatoriginate in the nerves and bone ofthe head and neck are even rarer. This bulletin also deals withcancer of the thyroid, a gland inthe neck that produces hormonesthat regulate metabolism. Likecancers of other sites in the headand neck, it is uncommon. In most

other respects, thyroid cancers areunlike UAT cancers, but theservices required for patientsoverlap.Survival rates: The prognosis forindividual patients dependsheavily on the stage of the diseaseand co-morbidities. Disease stagecan be described most precisely interms of the size of the initialtumour (T), the extent of lymphnode involvement (N), and thepresence or absence of metastaticspread (M). The system often usedin the UK ranges from Stage I(early disease) to IV (metastatic).Figures for stage at diagnosis andsurvival rates for UAT cancers forthe South and West of England aregiven in Table 3, below. Therelationship between this systemand TNM stage for each cancersite is complex, but details aregiven in the document from whichthese figures were derived.3

A.2 Risk factors Cancers of the UAT: Most UATcancers are related to alcohol andtobacco consumption, whichtogether probably account forthree-quarters of cases.4 Cigarette

smoking is associated withincreased risk of all of the morecommon forms of UAT cancer; therisk among cigarette smokers maybe ten or more times higher thanthat for non-smokers. Pipe or cigarsmoking is associated with an evenhigher excess risk of oral cancer.5

Chewing tobacco – with orwithout areca (betel) nut – isstrongly linked with oral andpharyngeal cancer, as well as tosome extent with cancer of thelarynx and the thyroid.6,7

High alcohol consumption andsmoking have synergistic ormultiplicative effects on the risk ofhead and neck cancer. For heavydrinkers who are also heavysmokers, the risk of oral cancer isover 35 times that for those whoneither smoke nor drink, and asimilar pattern is found withcancer of the larynx.4,8 Alcoholconsumption is a particularlyimportant risk factor for cancers ofthe mouth and pharynx and, to alesser degree, for cancer of thelarynx. Consuming 100g of alcoholor more per day (about twelveunits – six pints of beer or twelvemeasures of wine or spirits)multiplies the risk of developingoral cancer at least six-fold, afteradjustment for tobacco use; themore alcohol consumed, thegreater the risk.9

Diet also affects the risk of cancersof the oral cavity, pharynx andlarynx; as with many other formsof cancer, frequent consumption offruit and vegetables is associatedwith reduced risk. Poor diet isoften associated with heavysmoking and alcohol use, and themalnutrition that can resultexacerbates the risk of cancer. Thyroid cancer: A history ofradiation exposure to the neckarea is associated with increasedrisk of thyroid cancer, often after adelay of well over a decade; somecases can be traced to radiationtreatment in childhood. Bothdeficiency and excess of dietaryiodine are associated withincreased risk.10 Otherpredisposing factors includeprolonged stimulation withthyroid stimulating hormone(which can be due to chroniciodine deficiency), chroniclymphocytic thyroiditis(lymphoma), and genetic factors

Cancer site

Mouth, lip & oral cavity

Salivary glands

Pharynx (throat)

Nasal cavity, ear & sinuses

Larynx (voice-box)

Thyroid

ICD10 code

C00-06

C07-8

C09-14

C30-31

C32

C73

Number ofregistrations

2329

422

1339

352

1903

1131

Deaths

782

138

617

110

655

251

Men

5.9

1.0

4.0

0.8

6.6

1.3

Women

3.7

0.8

1.6

0.6

1.3

3.3


Men

1.8

0.3

1.7

0.3

2.1

0.3

Women

1.3

0.2

0.8

0.2

0.5

0.7

Mortality: cruderate per 100,000

Table 1 Registrations, incidences and deaths, England 20001

Cancer site

Mouth, lip & oral cavity

Salivary glands

Pharynx (throat)

Nasal cavity, ear & sinuses

Larynx (voice-box)

Thyroid

ICD10 code

C00-06

C07-8

C09-14

C30-31

C32

C73


166

47

90

21

147

57

Deaths

45

8

43

7

54

8

Men

7.1

1.6

4.7

0.9

9.0

1.3

Women

4.4

1.6

1.6

0.5

1.4

2.6


Men

1.8

0.3

1.9

0.4

3.0

0.1

Women

1.3

0.3

1.1

0.1

0.8

0.4

Mortality: cruderate per 100,000

Table 2 Registrations, incidences and deaths, Wales 20002

Stage

I early disease

II locally advanced

III tumour in lymph nodes

IV metastatic

Unknown

Two-yearsurvival,

crude rate(all sites)

89.7%

71.8%

57.6%

48.6%

69.8%

Larynxn=190

34

27

17

15

7

Oraln=241

21

16

15

34

11

Pharynxn=161

6

13

22

50

9

Salivaryglandn=56

13

17

7

28

35

Othern=79

12

8

8

47

25

Cancer site (% of cases at each stage at diagnosis)

Table 3 Cancer stage and survival in the South and West of England, 1999-20003

EFFECTIVE HEALTH CARE Management of head and neck cancers 32004 VOLUME 8 NUMBER 5

(linked with medullary thyroidcancer). Women are more thantwice as likely as men to developthyroid cancer.

A.3 Bulletin contextThe National Institute for ClinicalExcellence has now publishedguidance on head and neck cancerservices.11 As part of the guidancedevelopment process, reviewquestions were generated (for fulldetails see Appendix 2 of themanual). These questions do notaddress every aspect ofmanagement but those consideredkey to inform the production ofthe guidance. Systematic reviewsof the research evidence wereundertaken by the Centre forReviews and Dissemination (CRD)to answer these questions. Asummary of these reviews has alsobeen published.12 The guidancedocuments, including a patientsummary, can be obtained via theNICE website (www.nice.nhs.uk).The key recommendations fromthe guidance are given in SectionB below. This bulletin summarisesthe research evidence thatinformed the guidance.

B. KeyrecommendationsIn the guidance manual,11 thefollowing key recommendationswere identified as priorities for theNHS, which, if implemented,would make a major contributionto improving outcomes in headand neck cancers.

■ Services for patients with headand neck cancers should becommissioned at the cancernetwork level. Over the next fewyears, assessment and treatmentservices will become increasinglyconcentrated in cancer centresserving populations of over amillion.

■ MDTs with a wide range ofspecialists will be central to theservice, each managing at least100 new cases of UAT cancerper annum. They will beresponsible for assessment,treatment planning andmanagement of every patient.Specialised teams will deal withpatients with thyroid cancer,

and with those with rare orparticularly challengingconditions such as salivarygland and skull base tumours.

■ Arrangements for referral ateach stage of the patient’scancer journey should bestreamlined. Diagnostic clinicsshould be established forpatients with neck lumps.

■ A wide range of supportservices should be provided.Clinical nurse specialists, speechand language therapists,dietitians and restorativedentists play crucial roles but avariety of other therapists arealso required, from the pre-treatment assessment perioduntil rehabilitation is complete.

■ Co-ordinated Local SupportTeams should be established toprovide long-term support andrehabilitation for patients in thecommunity. These teams willwork closely with every level ofthe service, from primary careteams to the specialist MDT.

■ MDTs should take responsibilityfor ensuring that accurate andcomplete data on disease stage,management and outcomes arerecorded. Information collectionand audit are crucial toimproving services and must beadequately supported.

■ Research into the effectivenessof management – includingassessment, treatment, deliveryof services and rehabilitation –urgently requires developmentand expansion. Multi-centreclinical trials should beencouraged and supported.

C. ReferralDiagnosis and assessment of patientswith possible head and neck cancersrequires a sequence of activities thattake place at different levels of theservice. When patients first presentto their GP with symptoms, it isusually not obvious whether thepatient has cancer. Most will first bereferred to a local hospital ENT ormaxillofacial clinic, where cancerwill be found or strongly suspectedin a small minority of cases. Thesepatients require onward referral forfurther assessment, normally in atertiary centre.

Because head and neck cancer isrelatively rare, the average GPwould expect to see a new caseonly every six years; anotolaryngologist (ENT specialist) ormaxillofacial surgeon working in adistrict general hospital wouldexpect to see one new case everysix weeks. Some forms of oralcancer may be initially diagnosedby dentists, who are trained tocarry out a comprehensiveexamination of all areas of oralmucosa (gum and interior of themouth) when patients attend fordental care. Pharmacists may alsobe able to alert customers to theneed for investigation, for exampleif they frequently buy treatmentsfor mouth ulcers or are hoarse fora month or more.

C.1 Early detection of malignancy

Two observational studies provideevidence that patients whosecancers are detected later requiremore extensive treatment andexperience poorer outcomes.

An interview-based Brazilian studythat investigated delays in thereferral pathway showed that themajority (58%) of delays werecaused by patients delayingconsultation with healthprofessionals.13 However, healthprofessionals were solelyresponsible for delay in 13% ofcases and responsible for at leastsome of the delay in a further 11%of cases. The study assessedwhether patients who hadexperienced delays were morelikely to be diagnosed with latestage disease than those patientswho had experienced no delays.The assessment found thatpatients who did not delay inreporting symptoms to aprofessional were approximatelyhalf as likely to present with latestage disease. There was adramatic increase in hospital costswith more advanced disease.

An audit conducted in the West ofScotland region found that latestage presentation was common.14

Patients presenting with Stage 1disease fared significantly betterthan those presenting with all otherstages in terms of post-therapydisease-free interval. They also hada significantly better overall survivalrate than patients presenting withStage III or IV disease.

C.2 Raising professionals’awareness of the existence ofhead and neck cancersA brief, multi-componenteducational intervention designedto teach health care professionalsabout the oral sites at risk,aetiological factors and early signsand symptoms of oral andpharyngeal cancers, and screeningtechniques was assessed in a USstudy.15 Doctors, allied healthprofessionals and medical studentsdemonstrated increases inknowledge levels while thedentists and nurses participatingfailed to demonstrate increasedlevels of knowledge. Dentists werethe only group who did not feelthey needed additional trainingfollowing the intervention.This study suggests that aneducational intervention may bebeneficial but the professionalgrouping at which it is aimed maybe a factor in its usefulness. Thefailure of dentists and nurses toincrease their levels of knowledgemay be related to the level atwhich the intervention waspitched or its format. No patientoutcomes were measured.

C.3 Opportunistic screeningA UK study of the feasibility ofsystematic examination of the oralmucosa by dentists concluded thatthis could be carried out as part ofa routine dental inspection.16 A totalof 1,949 employees who benefitedfrom employer-sourced dentalhealthcare were invited to attend amucosal inspection session as partof their routine dental check-up;1,947 employees agreed and wereseen. One hundred and fifty-fivepatients (8%) were found to haveoral lesions. Of these, 151 werediagnosed as having innocent orbenign conditions, there were twocases of tobacco-associatedleukoplakia, one case of reticularlichen planus and one case ofsquamous cell carcinoma. However,this is a specific sub-population andwas not in an NHS setting.

C.4 Rapid access to a specialist/dedicated diagnostic clinicPersistent hoarseness: Twostudies examined ‘persistenthoarseness’ or ‘husky voice’clinics. A well-conducted study of271 patients who attended a directreferral, immediate-access hoarse

voice clinic found that the averagewaiting time for attendance at theclinic was three weeks.17 Thirty-nine (14%) patients were found tohave suspicious lesions on indirectlaryngoscopy at the clinic andwere admitted for directlaryngoscopy and biopsy underanaesthetic. Ten of these 39patients were diagnosed withcancer of the larynx, three werediagnosed with dysplasia and onewith cancer of the tongue. An audit of 34 patients referred to apilot ‘husky voice’ clinic withagreed referral protocols reportedthat 94% of patients were seenwithin five working days and fivereferrals (15%) were inappropriate.18

One case of cancer was reported.Lump and bump clinics: Threestudies were found whichexamined the effects of lump andbump clinics. One controlled studycompared two cohorts of 50patients referred to a ‘lump andbump’ clinic and found that themean time between the date of thereferral letter and the outpatientappointment increased from 13.8days to 25.4 days afterimplementation of the two-weekwait initiative.19 The pick-up ratefor malignancy was 4% in patientsreferred via the two-week waitinitiative and 14% for non-two-week wait ‘lump and bump’ clinicpatients. However, the possibleinfluence of other factorsoccurring at the same time as theimplementation of the two-weekwait initiative reduces thereliability of the results presented.An audit and re-audit of a ‘one-stop’ head and neck lump clinicwith the provision of immediatefine needle aspiration cytology(FNAC) assessment and reportingfound that over two-thirds of 245patients referred to the clinic weremanaged during only one visiteach.20,21 The accuracy ofimmediate FNAC was 94%. Themean number of days patientswaited to be seen in the clinic was17 in the first audit and 21 in there-audit and the mean waitingtime at the clinic was about anhour in both audits.Of 100 patients referred to a directreferral clinic for a neck mass, forwhich practitioners were advisedof the appropriate route of referral,46 were referred with enlarged

lymph nodes, 21 for thyroidswelling and 17 for salivary glandswellings.22 Two referrals wereconsidered to be inappropriate. Ofthe patients referred with enlargedlymph nodes, 10 were found tohave squamous cell carcinoma andthree had lymphoma. Four thyroidswellings and two salivary glandswellings were malignant.

D. Structure ofservicesD.1 Role of multidisciplinaryteams (MDTs)Professionals seem to value theopportunities afforded by the MDTsystem.23,24 Where appropriateprocedures are in place, goodclinical outcomes may bepromoted by management by aMDT.25

D.2 Types of staff involvedIt is generally accepted that a widerange of specialist support servicesshould be provided. Althoughthere is consensus that speech andlanguage therapists, dietitians,specialist nurses and restorativedentists can play crucial roles, thelimited evidence found in this areawas of poor quality and definitiveconclusions cannot be drawn.Speech and language therapists(SLTs). Data from three researchstudies26-28 which investigated theopinions of patients who hadundergone a laryngectomy suggestthat patients feel they benefit fromthe opportunity to see SLTs bothbefore and after surgery. Thefindings are limited by the weakdesigns used and poor reporting ofthe SLT interventions in thestudies. The age of the studies isalso of concern.Dietitians. Two studies were foundwhich suggest that interventionswhich may be advised by dietitiansor nutritionists have beneficialeffects on patients.29,30 The paucityof evidence and the low validity ofthe methods used in the researchstudies mean that this conclusionis only tentative.Specialist nurses. Specialistnursing care has not beenextensively studied in comparativestudies. The evidence located waseconomic in nature but did suggest


EFFECTIVE HEALTH CARE Management of head and neck cancers 52004 VOLUME 8 NUMBER 5

benefits of sub-specialisation innursing.31 No definitive conclusionsmay be drawn.

D.3 Location of servicesAn extensive UK focus-group studyfound that patients and relativeswere concerned about mixed sexand mixed speciality wards.23,24

They felt strongly that head andneck cancers should be managedon a dedicated ward or area withina ward, with adequate privacy andspecialist nursing skills.Professionals supported theproposal in theory, but some hadreservations about over-specialisation and the loss ofvariety in their work.

D.4 Volume and outcomesClinician volume. One studyexamined a series of 5,860 patientswho underwent thyroid surgicalprocedures between 1991 and1996.32 The complication rate fornon-unilateral subtotalthyroidectomy procedures wassignificantly higher in patientstreated by surgeons who operatedon fewer than ten patients than inthose whose surgeons operated onmore than 100 patients in thestudy period. The length ofhospital stay was lower in patientstreated by surgeons who operatedon more than 100 patients thanany of the other volume categoriesfor all surgical procedures; thedifference was statisticallysignificant in almost everycategory.

Hospital volume. In a retrospectivesurvey of Scottish cancer registrydata, the effects of hospital volumewere examined by comparing thelargest provider with the remainingproviders.14 The high-volumeprovider saw 124 (60%) of the total206 patients. The remaining 40%of patients were treated in 13 units.Patients treated at the high-volumeprovider had a significantly lowerrisk of death and a significantlylower risk of recurrence. Thisassociation between treatmentcentre and survival or risk ofrecurrence was not apparent whenthe treatment strategy wasincluded as a covariate. Thissuggests that the improvement inoutcomes for patients seen in thehigh-volume provider may, in partat least, be related to the choice oftreatments offered.

E. Initialinvestigationand diagnosisInitial investigation is usually byclose inspection of the affectedarea. When the lesion isinaccessible, endoscopy(pharyngolaryngoscopy) – usuallyusing a fibre-optic device insertedinto the pharynx and/or larynx – isessential. A definite diagnosis ofcancer requires the removal of asmall quantity of tissue formicroscopic examination, usingbiopsy when the lesion is on thelining of the mouth or airway, orfine needle aspiration for necklumps.

E.1 Fine needle aspirationcytology in patients withsymptoms suggestive of thyroidcancerIn a study investigating whethercore needle biopsy (CNB) providesadditional information over fineneedle aspiration biopsy (FNAB),29 patients diagnosed as havingthyroid nodules on ultrasound hadboth index tests, as well as adefinitive histological diagnosisafter surgery.33 However, 13 CNBsdid not provide sufficient materialfor diagnosis, so the respectiveaccuracy of the tests is onlyreported for 16 patients. Theaccuracy of FNAB was 94%compared with 100% for CNB. Thesensitivity of FNAB was 86% andthe specificity was 100%. Thesensitivity and specificity of CNBwere both 100%. The fact thatdiagnostic conclusions could onlybe drawn from 55% of CNBs, incontrast to 100% of FNABs,suggests that the overall efficacy ofFNAB is probably superior.However, the risk of false negativesneeds to be acknowledged. Due tothe small sample size this studyshould be regarded as suggestiverather than definitive.

E.2 Written informationA Canadian study investigatedrecall rates among head and neckcancer patients of a combined oraland written intervention.34 Theintervention consisted of anillustrated pamphlet and an oralexplanation of the possiblecomplications and risks of surgery.

When compared to patients whoonly received the oral explanation,the patients who also received thepamphlet were statisticallysignificantly more likely to recallthe potential complications of theprocedure (mean recall rate 50%versus 30%; p < 0.001).This study was described by itsauthors as being a randomisedcontrolled trial (RCT) but they didnot report the method ofrandomisation, nor whetherblinding of the outcome assessorswas used. Patient outcomes otherthan ability to recall what hadbeen told to them were notmeasured. These factors may affectthe generalisability of the resultsbut the marked differences in therecall rates could still beconsidered supportive of writteninformation packages. Three studies from the UK alsosuggest that written informationmay be helpful to patients.35-37

Written information is sometimesused in isolation, but when it isused in combination with othermeans of communication therelative effects of the variousconcurrent interventions cannotbe identified. Nevertheless, theevidence suggests that writteninformation has a role to play inthis setting.

F. Pre-treatmentassessment andmanagementVarious forms of imaging may beused to stage head and neckcancer; that is, to discover the sizeand extent of the primary tumourand to find out if it has spread tonearby lymph nodes or to moredistant sites (metastases). Inpractice, staging at the time ofinitial assessment may not beaccurate and the speed at whichany particular tumour may grow isnot known, so predicting prognosisis difficult. Also, the patient’sgeneral health has a marked effecton survival.

F.1 Effectiveness of imaging inassessing chest involvementTwo studies compared theeffectiveness of X-rays with CT for

screening for tumours in the chestin patients with head and neckcancers.38,39 Both found that CTwas significantly more sensitive,but the specificity of X-ray imagingwas slightly higher. However,given the methodologicallimitations in both of the studies,the results should be interpretedwith caution.

F.2 Nutritional assessmentTwo studies suggest that earlynutritional assessment andintervention, includingpercutaneous gastrostomy (PEG)insertion, appears to be effective inpreventing weight loss anddehydration in head and neckcancer patients undergoingradiotherapy.30,40

F.3 Dental assessmentThe results of four studies withrelatively large sample sizessuggest that dental assessmentprior to radiotherapy for head andneck cancer is beneficial. Themajority of patients in each studyrequired dental treatment beforethe commencement ofradiotherapy.41-44

Radiotherapy can cause adverseeffects on the jaw, teeth and oralcavity, such that specialised dentalmanagement may also be requiredafter treatment.45

F.4 Shared decision-makingInformation from one qualitativestudy of head and neck cancerpatients and their professionalcarers suggests that patients oftenwant to be involved in decidingthe course of their treatment butmany feel excluded from thedecision-making process.23,24

Doctors differed in the degree towhich they believed patientsshould be involved in decision-making, but felt that they oftendid not provide patients with thefull range of options or theinformation required to decidebetween different treatments.

F.5 Availability of psychosocialcareSeveral studies were found whichinvestigated the effects ofpsychosocial care.46-51 While thetypes of psychosocial interventionsand methods used varied betweenthe studies found, most of theresearch suggested that

psychosocial care was beneficial topatients with head and neckcancer. This was true of all of theexperimental studies located.However, the methodologicalflaws and the lack of reliabilityinherent in the methods usedmean that the findings are at bestsuggestive.

F.6 Availability of counsellingInformation from one qualitativestudy of head and neck cancerpatients suggests that somepatients wish to receivecounselling but that they are notoften offered this facility.23,24

Patients appeared to want someonewith whom to discuss theirproblems, rather than someonewho would offer solutions withoutlistening closely to them.

F.7 Provision of a patient visitorIt appears from five attitudinalsurveys that patients who haveundergone laryngectomy are keento have contact with rehabilitatedpatients who have previouslyundergone the sameprocedures.23,24,26-28,35 The individualpreferences of the patient shouldbe taken into account in decidingthe timing of the meeting.

F.8 Smoking cessationprogrammesIn a RCT, 186 newly diagnosedhead and neck cancer patients(88% of whom were currentsmokers) were randomised toeither a 12-month smokingcessation programme or usual careadvice.52,53 70% of patientsfollowed-up for a year werecontinuous abstainers, but therewere no significant differencesbetween the groups. No adverseeffects were reported. Given thelack of methodological detailsreported, the results should beinterpreted with caution.

G. PrimarytreatmentMost head and neck cancers aretreated with surgery orradiotherapy or a combination ofboth. Chemotherapy alone israrely appropriate for these formsof cancer, but chemotherapeutic

agents are sometimes used toenhance the effects ofradiotherapy; this is known aschemoradiation. Reconstructivesurgery and specialised dentistryare often needed. Patients needconsiderable help and supportwith nutrition andcommunication, both during andafter primary treatment. Thyroid cancers are usually treatedby surgical removal of the thyroidgland. Radioiodine treatment,which requires special protectedrooms, may be used to destroyresidual disease. Endocrinologistsplay important roles in themanagement of patients treated forthyroid cancer, who requirethyroid hormone replacementtherapy and monitoring for therest of their lives. The cancer canrecur many years after primarytreatment, but most patients willremain free from it.

G.1 Relative efficacies oftreatment modalitiesThe evidence suggests thatconcomitant chemotherapyincreases survival and loco-regional control for patients withhead and neck cancer, but nostatistically significant survivalbenefit has been demonstratedwith adjuvant or neoadjuvantchemotherapy (other than in asubgroup analysis which detectedsignificantly improved survivalwith neoadjuvant chemotherapyusing 5-fluorouracil incombination with either cisplatinor carboplatin).54-58 The evidencerelating to specific agents iscontradictory with regard to theefficacy of platinum-basedchemoradiation.Patients with newly diagnosedlocally advanced nasopharyngealcancer treated withchemoradiation had significantlyhigher rates of disease-freesurvival than patients treated withradiotherapy alone.59 This wasfound for neoadjuvantchemotherapy, concurrentchemotherapy and concurrentadjuvant chemotherapy. The useof concomitant chemotherapy hasbeen found to significantlyenhance both acute and lateradiation morbidity effects. In a large trial of patients withnewly diagnosed, locally advanced


head and neck cancer, two-yearloco-regional control rates werehigher in patients receivingaccelerated radiotherapy with aconcomitant boost orhyperfractionated radiotherapythan those receiving acceleratedradiotherapy with a split course orconventional treatment. However,overall survival was notstatistically significantly differentbetween the arms.60,61 Trials havereported increased acute toxicitywith accelerated radiotherapycompared with conventionalradiotherapy. Hyperfractionatedradiotherapy has been associatedwith increased mucosal and skintoxicity compared withconventional radiotherapy. Areduction in the risk of death hasbeen found in patients receivinghyperfractionated radiotherapyover those receiving conventionalradiotherapy in one review;62

patients treated withhyperfractionation were less likelyto respond incompletely totreatment or to suffer localrecurrence. In a larynx preservation trialpatients allocated to a concomitantchemotherapy and radiotherapygroup had significantly greaterloco-regional control and larynxpreservation than patientsallocated to neoadjuvantchemotherapy or radiotherapyalone. In another study patientswho had been randomised toneoadjuvant chemotherapy incombination with radiotherapyscored significantly better inmental health and painassessments than patients whohad been randomised to surgeryand radiotherapy.56

G.2 Adherence to a treatmentprotocol and specified timescalesThe results of two cohort studiessuggest that the introduction of aclinical care pathway may reducethe average length of hospital stayand total costs.63,64

G.3 Adherence to specifiedradiotherapy timescales

A systematic review of individualpatient data found that compliancewith the prescribed radiationtherapy schedule was relativelypoor, with an agreement betweenoverall and ideal treatment time in

only 30% of cases; 7% completedtreatment sooner than planned.65

Clinical outcomes were notevaluated.

A reanalysis of data from two RCTsincluding 828 patients found thatonly 278 patients had receivedradiotherapy exactly as per theirprotocol.66 The analysis identified atime factor of 0.8Gy per day as theextra dose required to counteractthe reduction in tumour controlprobability with extension of thetreatment time. Despite thetheoretical nature of thecalculations, the results appear tobe valid. Again, clinical outcomeswere not evaluated.

Four other studies found thatprolonged overall treatment timeled to worse loco-regional controland disease-free survival.67-70 In thereanalysis of data from theconventional arm of the CHARTtrial,68 patients receivingradiotherapy for 49 days or more(mean 51.5 days) had an increasein relative risk of death of 19%compared with patients receivingradiotherapy for 48 days or fewer(mean 45.7 days). When adjustedfor factors collected beforetreatment, the increase in risk ofdeath was 9%. In the case-controlstudy,70 12% of patients in thecontinuous course radiotherapygroup and 17% of patients in thesplit course radiotherapy grouphad prolonged overall treatmenttime (treatment that extendedmore than one week beyond theschedule). Each day of interruptionof treatment was found to increasethe hazard rate for reduced loco-regional control by 3.3% anddisease-free survival by 2.9%.

G.4 Delays in initiatingradiotherapy

A systematic review was foundwhich included four RCTs and 42case series, of which 12 case seriesrelated to head and neck cancer.71

Of these, five related to primaryradiotherapy (n=2,427) and sevento post-operative radiotherapy(n=851).

The five studies of delays ininitiating treatment in patientsbeing treated primarily withradiotherapy suggested that suchdelays may adversely affect loco-regional control rates. However,

the findings were contradictory.One of these studies suggestedthat long-term survival wasimproved for those treated sooner.

Seven studies of delays ininitiating treatment in patientsbeing treated with postoperativeradiotherapy indicated that delaysin initiating radiotherapy adverselyaffect loco-regional control rates.Two of these studies reportedcontradictory findings relating tolong-term survival.

Insufficient information waspresented in the review to identifyan appropriate time frame foreither the period from diagnosis totreatment initiation or fromsurgery to initiation ofradiotherapy.

G.5 Interventions for theprevention and/or treatment ofmucositisThe evidence relating to head andneck cancer patients suggests thatthe use of prophylactic narrow-spectrum antibiotics is beneficialfor preventing severe oralmucositis in patients receivingradiotherapy.72 Amifostine wasbeneficial in patients undergoingchemoradiotherapy; it did notaffect the anti-tumoureffectiveness of radiotherapy and itrarely produced severe adverseeffects. It was not found tosignificantly benefit head and neckcancer patients undergoingradiotherapy without concurrentchemotherapy.73

In cancer patients receivingchemotherapy or radiotherapytreatment, ice chips and GM-CSFprevented mucositis and antibioticpaste or pastille and amifostineprovided moderate and minimalbenefits in preventing mucositis,respectively.74 Hydrolytic enzymesreduced the severity of mucositis,as did allopurinal, although theevidence for the latter wasunreliable.

G.6 Interventions to reduce theseverity of the symptoms ofxerostomia

Three reviews were found inwhich pilocarpine hydrochlorideand amifostine were found tosignificantly reduce the effects ofradiation-induced xerostomia (drymouth) in patients with head and

2004 VOLUME 8 NUMBER 5 EFFECTIVE HEALTH CARE Management of head and neck cancers 7


neck cancer.73,75,76 Adverse effects ofboth agents were common, but notsevere or life threatening.However, these conclusionsshould be interpreted with cautionowing to the lack of informationabout the methods used in two ofthe reviews and possibleheterogeneity between includedstudies.

H. After-care andrehabilitationLiving with the effects of head andneck cancer can be difficult forboth patients and carers.Radiotherapy can be debilitating,with many persistent side-effects,and people can have difficultieswith speaking, chewing andswallowing, which can add toproblems with nutrition. Thosewho have undergonelaryngectomy (surgical removal ofthe larynx) must permanently copewith breathing through anopening in the neck (stoma) andwith dealing with any secretionscoughed out through the stoma,as the airway is completelyseparated from the gullet (pharynxand oesophagus). These patientsneed to learn to communicate in anew way. Those who undergo oraland facial surgery may facedifficulties with eating, drinkingand talking, and may have to learnto live with facial disfigurement.Such patients need specialisedsupport from a variety ofprofessionals, particularlyspecialist nurses, speech andlanguage therapists, and dietitians.

H.1 Rehabilitation services The review did not locate anywell-designed studies of theeffectiveness of speech andlanguage therapy, as provided inthe NHS. The majority of identifiedstudies were retrospective innature, with potential biases and alack of detail on the content ofspeech and language therapyinterventions.26,77-87 However,questionnaire-based studies andcase series reports support theview that speech and languagetherapy is beneficial in therehabilitation of patients withhead and neck cancer. One case

series study of art therapy wasidentified which suggested thatthere may be a role for art therapyfor patients with laryngeal cancer.88

However this result was based onthe opinions of the therapist ratherthan patients.

H.2 Osseointegrated implantsA number of studies were foundwhich investigated the outcomesof dental and facial bonerestoration using prosthesesretained by osseointegratedimplants.89-101 In view of thepotential biases in these studies, noconclusions on the effectiveness ofthe interventions reported can beregarded as reliable. It appears thatthe probability of osseointegrationmay be reduced in patients whohave had radiotherapy. Someevidence exists that suggests thathyperbaric oxygen therapy mayameliorate the effect ofradiotherapy on osseointegration.While treatment-related factorshave an important influence on theoutcome of osseointegrationprocedures, it appears thatanatomical factors may play anespecially important role. Graftedbone appears to be more likely topermit osseointegration than localbone and integration is more likelyin the mandible than in themaxilla.

H.3 Patient support groupThree surveys and a case seriessuggest that patients who aremembers of support groups derivebenefits from theirmembership.23,24,102-104

H.4 Patient education groupPatients who attended a monthlyeducational self-help groupreported satisfaction with thegroup and suggested that they hada better understanding of cancer,of the views of patients anddoctors and of reconstructivepossibilities.105 However, very fewmethodological details of thisqualitative study were reported.Fourteen Swedish patients whoattended a one-week psycho-educational programme a yearafter diagnosis appreciated allactivities, learned new things,considered this knowledge usefuland would recommend a week ofrehabilitation in this format toother cancer patients.47

H.5 Patient held recordsThe majority of respondents withhead and neck cancer who weregiven a logbook, containingsections on communication andinformation, had read the wholelogbook and said that it clarifiedthings for them.106 Respondents ina control group who were notgiven the logbook were morelikely to have fear, anxiety,depression and tension, but therewere no differences in theincidence of loneliness, insomnia,loss of control or reduction in self-esteem. The majority ofprofessionals involved in treatingpatients who had received thelogbook thought it was a goodmeans of information-giving and itmade a considerable contributionto the continuity of information. Itwas also useful in givingprofessionals an overview of thepatient’s case history andcontributed to harmonising carebetween professionals.

I. Follow-up andrecurrent diseasePeople who have been treated forUAT cancers remain at high risk,both of developing recurrentdisease and of new cancers in thehead and neck region and otherparts of the body such as thelungs. Careful follow-up andsystems for rapid referral forspecialist assessment andtreatment are therefore essential.

I.1 Routine follow-upOne systematic review thatassessed 37 different strategies forfollowing up patients treated forUAT cancer was identified.107 Thesestrategies were either common toall forms of UAT cancer (n=12) orspecific to individual UAT cancers(n=25). Results were presented interms of the number of times in a5-year follow-up strategy anintervention was recommended.Cost information was reported, butdifferences in patients’ outcomeswere not presented. Every strategyrecommended follow-up clinicconsultations for detectingdeterioration in the status of thepatient. Chest X-rays wererecommended by 10 of 12 general

strategies and 21 of 25 site-specificones. Blood counts (7 of 12 generaland 6 of 25 site-specific) and liverfunction tests (2 of 12 general and11 of 25 site-specific) were the onlyother tests widely recommended.The review reported few detailsabout its methods or the includedstudies. The validity ofcontributing studies was notassessed, which could affect thevalidity of the review.

I.2 Imaging in the detection ofrecurrenceIn a well-conducted diagnosticstudy that compared CT with MRI,both CT and MRI were found tohave relatively low sensitivity (44-67% for CT and 56% for MRI) andmoderate specificity (64-69% forCT and 78-83% for MRI) indetecting tumour recurrence andin distinguishing recurrence frompost-radiation therapy changes.108

However, MRI was found to bemore accurate than CT (73-78%compared with 64%). Two studies which compared CTwith PET in patients with asuspected recurrence found thatPET was more accurate thanCT.109,110 A study which comparedCT, PET and Colour-DopplerEchography (CDE) found that theaccuracy of CT and CDE werecomparable at 79% each, but theaccuracy of PET was superior at86%.111 In a study which comparedultrasound with PET, PET wasfound to be more accurate thanultrasound (86% versus 64%).112

Overall the evidence reviewedconsistently showed both MRI andPET to be more accurate than CTin detecting a recurrence of headand neck cancers. PET was alsofound to be more accurate than CTin patients where a recurrence wasclinically suspected. The accuracyof CDE was found to be similar tothat of CT. PET was also found tobe more accurate than ultrasound.

J. Palliativeinterventionsand carePalliative care aims to maintainpatients’ comfort and dignity, and

primary care teams play animportant role in providing suchcare. Whilst all professionalsworking with patients may addresspalliative care needs, palliativecare specialists, working inhospitals, hospices or thecommunity, are likely to berequired to support patients withadvanced disease. As many as half of all patients withUAT cancers are likely to die of thedisease eventually, and most willrequire palliative interventions;however, most of those treated forthyroid cancer enjoy good long-term health. For patients with latestage disease, good nursing careand palliative measures such aspain control and interventions tohelp them eat and breathe arecrucial; those who are expected tolive for a significant period maybenefit from palliative surgery,radiotherapy or chemotherapy. J.1 Palliative treatmentEvidence from one relatively smallstudy suggests that chemotherapy,given in combination withradiotherapy, may significantlyimprove disease-free survival inpreviously untreated patientsbeing treated palliatively fororopharyngeal cancers (Stages IIIto IV) in the short term. Thecomplete response rate of patientstreated by chemoradiotherapy was39% higher than that of patientstreated by radiotherapy alone. Thisdifference was statisticallysignificant (p=0.015).113 Moreresearch is required to assesslonger-term benefits.J.2 Assessment by a pain controlserviceOne study was identified thatassessed the services offered by apain control service to terminallyill head and neck cancer patientsundergoing palliative care.114

Patients were prescribed analgesiain accordance with the WHO paincontrol ladder. All patients weregiven regular medication; the ‘asneeded’ approach was avoided.The main outcome measurerelating to the intensity of painused in the study was a VisualAnalogue Scale (VAS). The meanVAS score (which has a maximumof 10) was 4.7 before analgesictherapy and 1.9 after initiation oftherapy. This difference was

statistically significant (p<0.001).However, few patients completedthe third recording of the VAS,intended to give longer-termresults.Since all patients were assessed bythe pain control service, it isdifficult to ascertain if theassessment had an effect on theoutcome over and above theintervention that was decidedupon by the service.

Appendix – research methodsThis document presents a summaryof a series of reviews undertaken byresearchers at the Centre for Reviewsand Dissemination (CRD), Universityof York. The review teamconstructed review questions inconsultation with the editorial groupand other experts in the field.Comprehensive searches werecarried out for each review question.Where appropriate, strategies werelimited by methodological searchfilter or date. Searches wereconducted for each question from arange of databases (MEDLINE,EMBASE, CancerLit, The CochraneLibrary, Database of Abstracts ofReviews of Effects (DARE), AMED,HMIC databases (King's Funddatabase, DH-Data and HELMIS),CINAHL, British Nursing Index, NHSEconomic Evaluation database (NHSEED) and SIGLE). Unpublished datawere also identified throughpersonal contact with researchers inthe field. Two additional databases(Science Citation Index and SocialScience Citation Index) weresearched for one question each toassess their relevance to the review.However, it was found that theirresults did not yield any additionalrelevant studies over the otherdatabases searched, so they were notused. Full details of the searches andstrategies used are available fromCRD (Tel: 01904 321846 or email:[email protected]). Literature searches were undertakenbetween October 2002 and April2004. Two reviewers screened titles andabstracts of all studies identifiedthrough electronic searching forrelevance. Potentially eligible studieswere retrieved in full and tworeviewers selected studies. Selectionof studies was based on pre-definedinclusion/exclusion criteria thatspecified for each question theparticipants, intervention,


comparator(s) and outcomes ofinterest. The sameinclusion/exclusion criteria wereapplied to studies identified fromnon-electronic sources.Disagreements were resolvedthrough discussion and anyunresolved disagreements werediscussed with a third reviewer. Norestriction was made on publicationlanguage. Data were extracted fromthe included studies by one reviewerand checked for accuracy by anotherreviewer. However, some studiesreported only as non-Englishlanguage publications could not bedata extracted (e.g. studies publishedin Japanese). Studies published inGerman, Dutch, Italian, Spanish andFrench were data extracted by onereviewer (sometimes it was onlypossible to extract minimal dataowing to the language problems)and checked by a second reviewer.

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Effective Health Care bulletins are published in association with Royal Society of Medicine Press. The National Institute for Clinical Excellence(NICE) funds a limited number of these bulletins for distribution to decision makers. Subscriptions are available to ensure receipt of a personalcopy. Subscription rates, including postage, for bulletins in Vol. 8 (6 issues) are: £53/$82 for individuals, £86/$130 for institutions. Individualcopies of bulletins from Vol. 5 onwards are available priced at £9.50. Discounts are available for bulk orders from groups within the NHS in theUK and to other groups at the publisher’s discretion.

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Enquiries concerning the content of this bulletin should be addressed to Centre for Reviews and Dissemination, University of York, York YO105DD; Telephone (01904) 321040; Fax (01904) 321041; email [email protected] Centre for Reviews and Dissemination, 2004. NHS organisations in the UK are encouraged to reproduce sections of the bulletin for their own purposessubject to prior permission from the copyright holder. Apart from fair dealing for the purposes of research or private study, or criticism or review, as permitted underthe Copyright, Designs and Patents Act, 1988, this publication may only be produced, stored or transmitted, in any form or by any means, with the prior writtenpermission of the copyright holders (Centre for Reviews and Dissemination, University of York, York YO10 5DD).

Funding for the bulletin is provided by NICE. The Centre for Reviews and Dissemination is funded by the NHS Executive and the Health Departments of Wales andNorthern Ireland. The views expressed in this publication are those of the authors and not necessarily those of NICE, the NHS Executive or the Health Departments ofWales or Northern Ireland.

Printed and bound in Great Britain by Latimer Trend & Company Ltd., Plymouth. Printed on acid-free paper. ISSN: 0965-0288The contents of this bulletin are likely to be valid for around one year, by which time significant new research evidence may have become available.

The Effective Health Care bulletins arebased on systematic review andsynthesis of research on the clinicaleffectiveness, cost-effectiveness andacceptabil i ty of health serviceinterventions. This is carried out by a research team using establishedmethodological guidelines, withadvice from expert consultants foreach topic. Great care is taken to ensure that the work, and the conclusions reached, fair ly and accurately summarise theresearch findings. The University ofYork accepts no responsibility for anyconsequent damage arising from theuse of Effective Health Care.

Vol. 3

1. Preventing and reducingthe adverse effects ofunintended teenagepregnancies

2. The prevention andtreatment of obesity

3. Mental health promotion inhigh risk groups

4. Compression therapy forvenous leg ulcers

5. Management of stableangina

6. The management ofcolorectal cancer

Vol. 4

1. Cholesterol and CHD:screening and treatment

2. Pre-school hearing, speech,language and visionscreening

3. Management of lungcancer

4. Cardiac rehabilitation5. Antimicrobial prophylaxis

in colorectal surgery6. Deliberate self-harm

Vol. 5

1. Getting evidence intopractice

2. Dental restoration: whattype of filling?

3. Management ofgynaeological cancers

4. Complications of diabetes I5. Preventing the uptake of

smoking in young people6. Drug treatment for

schizophrenia.

Vol. 6

1. Complications ofdiabetes II

2. Promoting the initiation ofbreast feeding

3. Psychosocial interventionsfor schizophrenia

4. Management of uppergastro-intestinal cancer

5. Acute and chronic lowback pain

6. Informing, communicatingand sharing decisions withpeople who have cancer

Vol. 7

1. Effectiveness of laxativesin adults

2. Acupuncture3. Homeopathy4. Interventions for the

management of CFS/ME5. Improving the recognition

and management ofdepression in primary care

6. The prevention and treat-ment of childhood obesity

Vol. 8

1. Inhaler devices for thetreatment of asthma andCOPD

2. Treating nocturnal enuresisin children

3. The management ofcolorectal cancers

4. Effectiveness ofhypertensive drugs inblack people

Full text of previous bulletins available on our web site: www.york.ac.uk/inst/crd

This bulletin is based on a series ofsystematic reviews carried out bythe Centre for Reviews andDissemination to inform theproduction of the guidance onhead and neck cancer services.Full details are provided inGuidance on cancer services:improving outcomes in head andneck cancers: the manual and theresearch evidence published byNICE. These may be obtained freeof charge by calling the NHSResponse Line on 0870 1555 455.

This bulletin was written andproduced by staff at the Centre forReviews and Dissemination,University of York.

Acknowledgements

Effective Health Care would like toacknowledge the helpfulassistance of the following whocommented on the text:

■ Graham Cox, Oxford RadcliffeHospitals NHS Trust

■ Bob Haward, Northern andYorkshire Cancer Registry andInformation Service

■ Dee Kyle, Bradford South andWest PCT

■ Arabella Melville, Porthmadog,Gwynedd

■ Colin Pollock, RegionalDirectorate of Public Health(Yorkshire and Humber)

■ Nick Slevin, Christie Hospital NHSTrust

■ Stephen Worrall, BradfordTeaching Hospitals NHS Trust

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