Estimation of an Optimal External Beam RadiotherapyUtilization Rate for Head and Neck Carcinoma

Geoff Delaney, M.B.B.S., M.D.

Susannah Jacob, M.B.B.S., M.D.

Michael Barton, M.B.B.S.

Collaboration for Cancer Outcomes Research andEvaluation, Liverpool Hospital, Sydney, Australia.

Supported by a grant from the Australian Com-monwealth Department of Health and Ageing.

The authors thank Professor L. Peters, Dr. D.Dalley, Dr. K. Clark, Dr. M. Veness, Dr. R. Smee,and the members of the Steering Committee of theAustralian National Cancer Control Initiative forcomments concerning the study design and radio-therapy utilization trees.

Address for reprints: Geoff Delaney, M.B.B.S.,M.D., Collaboration for Cancer Outcomes Researchand Evaluation, Liverpool Hospital, Locked Bag7103, Liverpool, New South Wales, 1871, Austra-lia; Fax: (011) 61 2 9828 5299; E-mail:geoff.delaney@swsahs.nsw.gov.au

Received June 29, 2004; revision received Janu-ary 19, 2005; accepted February 4, 2005.

BACKGROUND. Radiotherapy is used commonly in the treatment of patients with

head and neck carcinoma. The benchmark radiotherapy utilization rates for head

and neck carcinoma largely are unknown. The objective of the current study was

to determine the optimal radiotherapy utilization rate for patients with head and

neck carcinoma and to compare this optimal rate with actual utilization rates

where actual utilization data were available.

METHODS. An optimal radiotherapy utilization tree was constructed that depicted

all patients with head and neck carcinoma in whom radiotherapy was indicated

according to evidence-based treatment guidelines. The proportions of patients

with clinical attributes that indicated possible benefit from radiotherapy were

obtained from epidemiological data and were inserted into the utilization tree. The

optimal proportion of patients with carcinoma of the head and neck who should

receive radiotherapy was calculated by merging the evidence-based recommen-

dations with the epidemiological data in the tree. Optimal rates of radiotherapy

utilization were compared with actual rates obtained from population-based stud-

ies.

RESULTS. Radiotherapy was indicated at some point during their illness in 74% of

all patients with head and neck carcinoma. By subsite, the optimal radiotherapy

utilization rates were oral cavity, 74%; lip, 20%; larynx, 100%; oropharynx, 100%;

salivary gland, 87%; hypopharynx, 100%; nasopharynx, 100%; paranasal sinuses,

100%; and unknown squamous cell carcinoma of the head and neck, 90%. All

treatment recommendations were based on Level III or IV evidence. Assessment of

actual radiotherapy utilization rates indicated an increased use of radiotherapy

over time for head and neck carcinoma. However, there also were some decreases

in the use of radiotherapy for some carcinoma subsites over the past 20 years,

despite the lower actual rates compared with the optimal rates. The reasons for

these reductions in use were not identified.

CONCLUSIONS. The actual radiotherapy utilization rate for patients with head and

neck carcinoma corresponded reasonably closely to the optimal rate for some

populations but also identified some shortfalls for other patient groups. The results

of this study provide a way of assessing shortfalls in radiotherapy. Cancer 2005;

103:2216 –27. © 2005 American Cancer Society.

KEYWORDS: head and neck carcinoma, laryngeal carcinoma, radiotherapy, utiliza-tion rate.

Radiotherapy is an essential treatment for malignant disease thatcontributes to the cure or palliation of many patients. Radiother-

apy facilities have high initial capital costs, and their operation isstaff-intensive. One of the benchmarks of the adequacy of radiother-apy service provision is the proportion of patients with new diagnosesof malignancies who receive at least one course of radiotherapyduring the course of their illness (the radiotherapy utilization rate).

2216

© 2005 American Cancer SocietyDOI 10.1002/cncr.21084Published online 26 April 2005 in Wiley InterScience (www.interscience.wiley.com).

Overall radiotherapy utilization rates vary substan-tially within Australia and internationally,1– 6 with uti-lization rates ranging from 20% to 55% for all patientswith newly diagnosed disease. It is important to derivean optimal rate of radiotherapy utilization that isbased on the best available clinical and epidemiolog-ical evidence. Optimal radiotherapy utilization ratesfor breast carcinoma,7,8 lung carcinoma,9,10 gastroin-testinal malignancies,11,12 melanoma,13 gynecologicmalignancies, 14,15 and prostate carcinoma16 havebeen reported previously. In this report, we presentthe radiotherapy utilization results for head and neckmalignancies. The objectives of this study were toestimate the optimal proportion of all patients withhead and neck carcinoma who, according to the bestavailable evidence, should receive at least one courseof external beam radiotherapy at some time during thecourse of their illness and to compare the optimalradiotherapy utilization rate for head and neck carci-noma with current practice.

MATERIALS AND METHODSIndications for RadiotherapyWe defined an indication for external beam radiother-apy as a clinical situation in which radiotherapy is thetreatment of choice on the basis of evidence that it willproduce a better clinical outcome compared with theoutcomes produced by other treatment modalities(including no treatment) and in which the patient isan appropriate candidate for radiotherapy in terms ofperformance status indicators and the presence orabsence of comorbidities. The superiority of radio-therapy over other treatment options could be basedon survival, local control, or toxicity profile. Becausethe objective of this investigation was to assess theoptimal utilization rate for external beam radiother-apy, estimates for the use of brachytherapy were notincluded in the study.

Search Strategy and Selection CriteriaCurrently, there are no national Australian treatmentguidelines for the management of head and neck car-cinoma. International guidelines for the managementof head and neck carcinoma were identified. They arethe United States National Cancer Institute PhysicianData Query (PDQ) guidelines for head and neck car-cinoma,17–24 the British Columbia Cancer Agencytreatment guidelines,25–32 the National Comprehen-sive Cancer Network guidelines,33,34 the guidelines is-sued by the British Association of Otorhinolaryngolo-gists and Head and Neck Surgeons,35 and theEuropean School of Oncology guidelines.36 –38 Thelevel of evidence that supported each recommenda-tion for radiotherapy use was classified using the Aus-

tralian National Health and Medical Research Councilhierarchy of levels of evidence.39

Using the best evidence available, a list of indica-tions for radiotherapy in the management of head andneck carcinoma was created, as shown in Table 1, andan optimal radiotherapy utilization tree was gener-ated. In the radiotherapy utilization tree, each branchpoint represents an attribute (such as the stage of thetumor or whether clear surgical margins were present)that affects a radiotherapy treatment decision. Eachterminal branch of the tree shows whether or notradiotherapy is recommended for individuals whohave those particular clinical attributes.

An indication for radiotherapy may occur in theinitial stages of treatment or may be delayed (for in-stance, in patients who develop a local or distantrecurrence and who have not previously required ra-diotherapy as part of the original management). Pa-tients who require external beam radiotherapy werecounted only once, even if they had multiple indica-tions for radiotherapy at different stages in their ill-ness. This allowed comparison of the optimal ratewith the actual radiotherapy utilization rate (definedas the number of patients treated by radiotherapy forthe first time divided by the incidence of specific ma-lignancies during a defined period).

Incidence DataWe collected epidemiological data on the proportionof patients who had attributes for which radiotherapymay be indicated and ranked the relative quality ofepidemiological data using the hierarchy shown inTable 2. The source with the highest quality rankingwas used to determine the incidence of each radio-therapy indication. Australian epidemiological datafrom Australian national and state cancer regis-tries40,41 were used whenever possible, because theresults from this study will be used specifically to planfuture radiotherapy facilities in Australia. When na-tional data were unavailable, more specific data (suchas those of state cancer registries) were used for infor-mation pertaining to tumor stage and pathology. In-stitutional data from published articles were usedwhen higher levels of epidemiological data could notbe obtained.42–57

An important source of data was the South Aus-tralian Network of Hospital-Based Cancer Registries.58

The registries in the network are based in major teach-ing hospitals and include data on patients attendingthe seven largest cancer centers in South Australia,which manage � 50% or the cancer cases in the state.The network data base includes information on dis-ease stage that was not available in other state databases.

RT Utilization in Head and Neck Carcinoma/Delaney et al. 2217

We ranked the relative quality of epidemiologicaldata from various sources, as shown in Table 2, usinga modification of the hierarchy reported by Sackett.59

The hierarchy was modified to rank Australian datahigher than data from other countries, because theresults of this study will be used to plan future radio-therapy services in Australia. We used the highestranking source to calculate the frequency of each ra-diotherapy indication.

Performance status data that were specific to pa-tients with carcinoma of the head and neck could notbe identified and, thus, were not incorporated into thetree. However, for most patients with locoregional dis-

ease, the performance status has little impact on thechoice of treatment modality and may influence only thetreatment intent. For instance, radiotherapy (with orwithout chemotherapy) may be appropriate in a patientwho has an advanced head and neck primary tumor anda good performance status. The patient most probablystill will undergo radiotherapy (but with palliative intentand in the absence of chemotherapy) if he has a poorperformance status. Therefore, the omission of perfor-mance status from the tree should not make a largedifference to the optimal radiotherapy utilization rate.

There will be some circumstances in which a pa-tient with early-stage head and neck carcinoma who

TABLE 1Head and Neck Cancer: Indications for Radiotherapy and Levels and Sources of Evidence

Outcome no.in tree Clinical scenario Treatment indicated

Level ofevidencea Reference(s)b

Proportion of allhead and neckcancers

1 Oral cavity, Stages I–II, surgery, adversepathology

Surgery � post-op RT IV 17,25,33,35,42 0.02

2 Oral cavity, Stages I–II, surgery, no adversepathology, locoregional recurrence

Surgery � post-op RT IV 17,25 0.01 (0.02)

4 Oral cavity, Stages I–II, RT Radical RT III 17,25,33,35 0.015 Oral cavity, Stages III–IV Surgery � RT III 17,25,33,35 0.156 Lip, cosmetically excisable, locoregional

recurrence RT �/� surgeryRT � surgery IV 17,33 0.02

8 Lip, not cosmetically excisable RT III 17,26,33,35 0.029 Larynx, supraglottic, conservative surgery,

locoregional recurrenceRT IV 18,33 � 0.01

11 Larynx, supraglottic, not suitable forlarynx-preserving surgery

RT III 18,30,33,35,38 0.06

12 Larynx, glottic, and subglottic, Stages I–II,RT appropriate

RT III 18,30,33,35,38 0.07

14 Larynx, glottic, and subglottic, Stage III CT � RT III 18,33,38 0.0315 Larynx, glottic, and subglottic, Stage IV Surgery � post-op RT or RT � CT III 18,33,35,38 0.0416 Oropharynx RT � CT or Surgery � RT III 27,33,35,36 0.0817 Salivary gland, Stages I–II, low grade,

lymph node positivePost-op RT IV 33,35,37 � 0.01

18 Salivary gland, Stages I–II, low grade,lymph node negative, locoregionalrecurrence

Radical or post-op RT IV 22,31,33 � 0.01

20 Salivary gland, Stages I–II, high grade Post-op RT IV 22,31,33,35 0.0321 Salivary gland, Stages III–IV Post-op RT IV 22,31,33,35 0.0222 Hypopharynx Radical or post-op RT � CT III 20,28,33,35 0.0523 Paranasal sinus Radical or post-op RT III 23,33,35 0.0524 Nasopharynx CT � RT or RT alone III 21,29,33,35 0.0425 Unknown primary, N1–N2a, local or

regional recurrenceRT alone or surgery � RT IV 34,35 � 0.01

27 Unknown primary, N2b–N3 RT alone or surgery � RT IV 24,34 0.02Proportion of all patients with head and neck cancer who have

RT recommended0.74 (74%)

RT: radiotherapy; post-op: postoperative; �: with or without; CT: chemotherapy; NCI/PDQ: National Cancer Institute/Physician Data Query; NCCN: National Comprehensive Cancer Network; BCCA: British Columbia

Cancer Agency; FIGO: International Federation of Gynecology and Obstetrics; ABS: American Brachytherapy Society.a Levels of evidence: Level I, systematic review of all relevant randomized studies; Level II, at least one properly conducted randomized trial; Level III: well designed controlled trials without randomization (includes

trials with “pseudorandomization” or comparative studies); Level IV: case series. Adapted from the National Health and Medical Research Council’s levels of evidence (National Health and Medical Research Council,

199839).b Numbers in this column refer to the list of References.

2218 CANCER June 1, 2005 / Volume 103 / Number 11

normally would undergo surgery, instead, will un-dergo radiation due to severe comorbidities, poor per-formance status, or patient choice. Similarly, there willbe occasional patients with such poor performancestatus that no antitumor treatment is considered ap-propriate. These patients also are likely to be very rare.Omission of these patient groups from the radiother-apy utilization tree will not affect the overall optimal

radiotherapy utilization rate significantly, because thenumbers are comparatively small.

The issue of disease stage used in the tree wasproblematic, because the staging systems havechanged over time, and published reports frequentlydo not state specifically which staging system wasused. In addition, the incidence data were from dif-fering periods; hence, different staging systems have

TABLE 2Head and Neck Cancer: The Incidence of Attributes Used to Define Indications for Radiotherapy

Population or subpopulation of interest Attribute

Proportion of thepopulation withthe attribute

Quality ofinformationa Reference(s)

All registry cancers Head and neck cancers 0.04 � AIHW, 200140

All head and neck cancers Oral cavity cancers 0.28 � AIHW, 200140

Oral cavity cancers Stages I–II 0.45 � SA Cancer Registry, 200058

Oral cavity cancers, Stages I–II Surgery 0.90 � SA Cancer Registry, 200058

Oral cavity cancers, Stages I–II, surgery Adverse pathology 0.20 � Jones et al., 199242

Oral cavity cancers, Stages I–II, surgery, noadverse pathology Locoregional recurrence 0.19 � Wolfensberger et al., 200157

All head and neck cancers Lip cancer 0.22 � AIHW, 200140

Lip cancer Cosmetically excisable 0.89 � Zitsch et al., 199544

Lip cancer, cosmetically excisable Locoregional recurrence 0.09–0.14 �Zitsch et al., 199544 and

Rowe et al., 199245

All head and neck cancers Laryngeal cancer 0.20 � AIHW, 200140

Laryngeal cancer Supraglottic laryngeal cancer 0.28 � Spitz et al., 198846

Supraglottic laryngeal cancer Suitable for larynx-preserving surgery 0.16–0.26, 0.0 � Lee et al., 199047 andHinerman et al., 200248;see text

Supraglottic laryngeal cancer treated withlarynx-preserving surgery

Locoregional recurrence 0.16 � Orus et al., 200049

Laryngeal cancer Stage I–II 0.51 � SA Cancer Registry, 200058

Laryngeal cancer Stage III 0.21 � SA Cancer Registry, 200058

Laryngeal cancer Stage IV 0.28 � SA Cancer Registry, 200058

All head and neck cancers Cancer of the oropharynx 0.08 � AIHW, 200140

All head and neck cancers Salivary gland cancer 0.06 � AIHW, 200140

Salivary gland cancer Stage I–II 0.66–0.67 � Calerao et al, 199850; Spiroet al., 198951; andO’Brien et al., 198652

Salivary gland cancer, Stage I–II Low grade 0.24–0.32 � Spiro et al, 198951; O’Brienet al., 198652; and Northet al., 199053

Salivary gland cancer, low grade Lymph node positive 0.05 � Spiro et al, 198951

Salivary gland cancer, low grade, negativemargins Locoregional recurrence 0.26 � North et al., 199053

All head and neck cancers Cancer of the hypopharynx 0.05 � AIHW, 200140

All head and neck cancers Cancer of the paranasal sinus 0.05 � AIHW, 200140

All head and neck cancers Nasopharyngeal cancer 0.04 � AIHW, 200140

All head and neck cancers Unknown primary (head and neck) 0.02 � Sinnathamby et al., 199754

and Gran et al., 200055

Unknown primary (head and neck) N1–N2a 0.22–0.61 � Sinnathamby et al., 199754

and Nguyen et al.,199456

Unknown primary (head and neck), N1–N2a Local or regional recurrence 0.54 � Gran et al., 200055

AIHW: Australian Institute of Health and Welfare; SA: South Australia.a Quality of information/hierarchy for epidemiological data: �: Australian national epidemiological data; �: Australian State Cancer Registry; �: epidemiological data bases from other large international groups (e.g.,

Surveillance, Epidemiology, and End Results Program); �: results from reports of a random sample from a population; �: comprehensive multiinstitutional data base; �: comprehensive single-institutional data base;

�: multiinstitutional reports on selected groups (e.g., multiinstitutional clinical trials); �: single-institutional reports on selected groups of patients (adapted from Sackett, 198959).

RT Utilization in Head and Neck Carcinoma/Delaney et al. 2219

been used. For the radiotherapy utilization trees, thetreatment branches are based on the most recent stag-ing system, i.e., the 1997 American Joint Committeeon Cancer staging system.60 When old incidence datawere used, the old staging system was applied despitethe fact that the proportions in different stages maydiffer between the old and new staging systems. Thiswas a pragmatic decision, because it is unlikely thatthese changes in the staging system would alter theproportion of a particular stage dramatically and,thus, it should have no significant effect on the opti-mal radiotherapy utilization rate.

Optimal Radiotherapy Utilization RatesThe optimal utilization rate was calculated by deter-mining the incidence of each indication for radiother-apy. Summing these incidences yields the total opti-mal utilization rate for head and neck carcinoma. Thisoptimal utilization rate was then compared accordingto tumor histology and disease stage with actual uti-lization data obtained from patterns-of-care studies.

The trees and the epidemiological data were sentfor external review to a multidisciplinary panel of on-cology experts (from surgical, medical oncology, radi-ation oncology, palliative care, and nursing back-grounds). The review process was overseen by anindependent steering committee of general oncologyexperts that was convened by the National CancerControl Initiative (Australia).

RESULTSThe optimal radiotherapy utilization tree for head andneck carcinoma is shown in Figure 1. Each branch ofthe tree signifies an attribute that affects a manage-ment decision (e.g., the stage of the tumor, whethersurgical margins are clear, etc.). Above each branch inthe radiotherapy utilization tree is a description of thespecific attribute that has led to the treatment deci-sion. Each number below the branch signifies theproportions of the attribute based on epidemiologicaldata.

There were 27 possible outcomes or end branchesfor this radiotherapy treatment tree. We identified 21outcomes for which radiotherapy is indicated. All rec-ommendations for radiotherapy from evidence-basedguidelines were based on Level III or IV evidence,because there were no randomized data availablecomparing radiotherapy with other modalities. How-ever, there are randomized data supporting the use ofchemoradiation over radiation alone for patients withadvanced laryngeal carcinoma.61 Table 1 identifies theclinical situations in which radiotherapy is recom-mended, the level of evidence, and the guideline orsource of evidence for the recommendation. The out-

come numbers in the table correspond to terminalnodes or outcome positions in the tree. The last col-umn represents the incidence of each clinical indica-tion for radiotherapy as a proportion of all patientswith head and neck carcinoma. This is calculated bymultiplying the incidences of all the branches leadingup to the terminal branch. The sum of this column isthe optimal radiotherapy utilization rate for head andneck carcinoma. This is calculated at 0.74, i.e., 74% ofall patients with head and neck carcinoma shouldreceive radiotherapy based on the best available evi-dence. Table 2 shows the epidemiological data corre-sponding to each branch point and the source of thosedata as well as the hierarchical level of the data ob-tained. Analysis of head and neck carcinoma showsthat the optimal radiotherapy utilization rates for thevarious subsites were as follows: oral cavity, 74%; lip,20%; larynx, 100%; oropharynx, 100%; salivary gland,87%; hypopharynx, 100%; nasopharynx, 100%; para-nasal sinuses, 100%; and metastatic squamous neckcarcinoma of unknown origin, 90%.

Controversies in the Management of Head And NeckCarcinomaIn some instances, published treatment guidelines forhead and neck carcinoma were not sufficiently spe-cific in their recommendations to identify definiteclinical or pathologic attributes as indications for ra-diotherapy. This may reflect the relative paucity ofgood-quality evidence that exists for head and neckcarcinoma compared with other malignancies, such asbreast carcinoma. Examples in which the guidelineswere uncertain or vague and the strategies that wereused to overcome this uncertainty are described be-low.

Treatment of patients with Stage I–II carcinoma ofthe oral cavity may consist of either surgery or radio-therapy, both of which are considered equally effec-tive. Therefore, the actual treatment received may beaffected by selection and referral biases. The BritishColumbian treatment guidelines25 recommend theuse of radiotherapy alone for most patients with early-stage oral cavity carcinomas, citing excellent localcontrol and functional results (Level III or IV evi-dence). The National Cancer Institute PDQ statementon lip and oral cavity carcinoma17 states that surgeryor radiation therapy produce similar cure rates forpatients with early-stage carcinoma (Stage I and II) ofthe oral cavity. The PDQ17 recommends that thechoice of treatment should be dictated by the antici-pated functional and cosmetic results of treatmentand by the availability of specialist expertise and pa-tient preference. In Australia, the majority of early-stage oral carcinomas are treated with surgery. Be-

2220 CANCER June 1, 2005 / Volume 103 / Number 11

cause there is no clear evidence to support onetreatment modality over the other, the tree reflectscurrent practice in Australia. The South Australia Hos-pital Cancer Registry reported that 90% of patientswith Stage I–II carcinomas of the oral cavity under-went surgery,58 and this figure was used in the tree forthe calculation of the optimal radiotherapy utilizationrate. We have assumed that the other 10% of patientseither were considered medically inoperable or re-fused surgery. Some of the surgical patients in theSouth Australia Hospital registry also received radio-therapy, presumably due to the presence of adversepathologic features. For sensitivity analysis, the pro-portion of patients with Stage I–II disease who under-went surgery as primary therapy was modeled be-

tween 90% and 0% (i.e., at 1 extreme, 90% of patientsunderwent surgery; and, at the other extreme, all pa-tients received radiation). The reason why 1 extremewas set at only 90% of patients undergoing surgeryrather than 100% is that at least 10% of these patientsare likely to be medically unfit to undergo major sur-gery. There is further discussion below on sensitivityanalysis and the effect of this uncertainty on the finalestimates.

A subset of patients with early-stage carcinoma ofthe oral cavity who undergo surgery may have adversepathologic features that would warrant adjuvant ra-diotherapy. However, the specific pathologic featuresthat would indicate adjuvant therapy are not specifiedin the evidence-based treatment guidelines. Jones et

FIGURE 1. Optimal radiotherapy (RT) utilization tree for patients with head and neck carcinoma.

RT Utilization in Head and Neck Carcinoma/Delaney et al. 2221

al.42 reported retrospectively on the recurrence pat-terns of 49 patients who underwent surgery for StageI–II oral cavity carcinomas (tongue, retromolar tri-gone, floor of mouth, alveolar ridge, buccal mucosa,and hard palate). Pathologic factors that were associ-ated with an unacceptably high locoregional recur-rence rate were tumors invading � 5 mm in depth ortumors with positive margins. Patients who had thesefeatures represented � 20% of the entire surgicalgroup. The recurrence rate in patients who had noadverse pathology was not reported. Patients who de-velop a recurrence after surgery alone most likely willreceive radiotherapy at the time of recurrence (eitheralone or combined with surgery).

The management of lip carcinoma also was con-troversial. The National Cancer Institute PDQ state-ment states that surgery and radiation therapy bothare effective in the treatment of early-stage carcino-mas (Stage I and II) of the lip and that the choice oftreatment should be made based on the anticipatedresults (functional and cosmetic) of treatment and onthe availability of experts. The size of the lesion wouldbe the greatest determinant of the extent of resectionand, hence, the greatest determinant of cosmetic andfunctional results. However, a size cut-off recommen-dation for surgery is not mentioned. For the purposesof the radiotherapy utilization tree, a tumor size of 3cm was chosen arbitrarily as surgically excisable witha reasonable and acceptable cosmetic result based onexpert opinion. Sensitivity analysis modeling was un-dertaken by varying the tumor cut-off size for surgerybetween 2 cm and 4 cm. All patients with lesions largerthan the cut-off measurement were deemed to requireeither definitive radiotherapy or radiotherapy com-bined with surgery.

The management of Stage III laryngeal carcinomais controversial, with diverse treatment options rec-ommended by different guidelines. There have beenno randomized trials that compared outcomes be-tween the various treatment modalities. The PDQguidelines state that patients with Stage III diseasemay be treated either by surgery with or without post-operative radiotherapy or by definitive radiotherapy,with surgery reserved for salvage of radiation failures.The State of the Art Oncology, British Columbia, andPeter MacCallum Cancer Institute treatment guide-lines recommend radiotherapy (postoperative or de-finitive) for all patients. Contemporary Australianpractice is to preserve the larynx. In randomized tri-als,62–70 it was shown that larynx preservation withchemoradiotherapy (using laryngectomy for salvage)provided laryngeal preservation in the majority of pa-tients without any detrimental effect on survival com-pared with laryngectomy. Therefore, it is considered

reasonable to offer radiotherapy to all patients with T3laryngeal carcinoma and to reserve surgery for sal-vage.

Some guidelines state that a small proportion ofpatients with early-stage laryngeal carcinoma may un-dergo larynx-conserving surgery, such as hemilaryn-gectomy, although most of these guidelines (PDQ, Na-tional Comprehensive Cancer Network, and BritishColumbia Cancer Agency) state that radiotherapy isthe preferred treatment. The proportion of patientswith supraglottic laryngeal carcinoma who could un-dergo larynx-preserving surgery in preference to ra-diotherapy was varied between 0% (i.e., all patientswith supraglottic laryngeal carcinoma receive radio-therapy) and 26% (i.e., the proportion of patients withsupraglottic laryngeal carcinoma identified as suitablefor larynx preservation in a single, large head and neckpractice).48

Laser therapy and conservative laryngeal surgeryhave been described in the literature as treatmentoptions for some patients with early-stage glottic car-cinoma. These procedures have not been comparedwith external beam radiotherapy in a randomizedcontrolled trial, nor have the clinical attributes re-quired to select patients for these procedures beenidentified. Therefore, it is difficult to estimate the pro-portion of patients who may undergo these treatmentsinstead of radiotherapy. Because studies have notidentified the proportion of patients who may betreated with laser or conservative surgery, we per-formed sensitivity analysis for 0 –10% of patients withearly-stage glottic carcinoma being suitable for thesetreatments.

The indications for radiotherapy (either as defin-itive treatment or as adjuvant to surgery) in patientswith squamous cell carcinoma of unknown primaryorigin metastatic to the head and neck are controver-sial. Some groups, such as Maulard et al.,71 advocateroutine radiotherapy in patients with localized dis-ease. The main intent is to not only maximize locore-gional control in the neck but also to attempt to pre-vent the occult primary from becoming symptomatic.Others, like Sinnathamby et al.,54 advocate that mod-ern staging techniques obviate the routine use of ra-diotherapy for unknown primary and propose thatradiotherapy should be reserved for patients who areat higher risk of locoregional failure (particularly thosewith advanced neck disease). O’Mara et al.72 suggestneck dissection as treatment for patients with N1–N2Adisease, and Sinnathamby et al. discuss omitting ra-diotherapy for patients who have solitary lymph nodesmeasuring up to 6 cm (N1–N2A). The Peter MacCal-lum Cancer Institute has developed treatment path-ways for unknown primary squamous cell carcinoma

2222 CANCER June 1, 2005 / Volume 103 / Number 11

of the head and neck (unpublished results) in whicheither preoperative or postoperative radiotherapy isrecommended for patients who have � N2A disease,and radiotherapy is considered optional for patientswho have N1–N2A disease. In the radiotherapy utili-zation tree, patients with N1–N2A disease do not re-ceive radiotherapy; this is to avoid a bias toward over-estimating the overall optimal radiotherapy utilizationrate. Patients with � N2A disease routinely are recom-mended for radiation. However, in the sensitivity anal-ysis, the branch point underwent modeling, with theproportion of patients receiving postoperative radio-therapy varying between those with N1 disease andthose with N2A disease.

Sensitivity AnalysisSensitivity analysis assesses the impact of varying thevalue of uncertain data on the overall optimal radio-therapy utilization rate. For the head and neck radio-therapy utilization tree, five data items were identifiedas uncertain: 1) No data were identified to estimatethe proportion of patients with early-stage oral cavitycarcinoma who should undergo surgery. An arbitraryvalue of 0.9 was chosen based on reported practice inSouth Australia, and the sensitivity analysis varied thisproportion between 0% patients undergoing surgery(and all patients receiving radiation) and 90% of pa-tients undergoing surgery. 2) The ideal proportion pa-tients with carcinomas of the lip who should undergosurgery alone is uncertain, as discussed above. There-fore, we used incidence data to model between pa-tients who received radiotherapy for tumors that mea-sure � 4 cm in size as the smallest case scenario forradiotherapy (6% incidence) and tumors that measure� 2 cm as the greatest case scenario for radiotherapy(25% incidence). 3) The proportion patients with su-praglottic laryngeal carcinoma who could undergo lar-ynx-preserving surgery in preference to radiotherapywas varied between 0% (i.e., all supraglottic laryngealcarcinomas were treated radiotherapeutically) and26% (i.e., the proportion of supraglottic laryngeal car-cinomas identified as suitable for larynx preservationin a single, large head and neck practice). 4) Theproportion of patients with early-stage glottic carci-noma who are suitable to undergo conservative sur-gery was varied between 0% and 10%. 5) The propor-tion of patients with unknown primary squamous cellcarcinoma was varied between patients with lymphnode status N1 receiving radiation (22%) and pa-tients with lymph node status N2a (9%) receivingradiation.

To assess the impact of these uncertainties on theoverall estimate of the need for radiotherapy in allpatients with head and neck carcinomas, a univariate

sensitivity analysis was performed for each of the vari-ables. This is illustrated as a tornado diagram (see Fig.2), which is a set of one-way sensitivity analysesbrought together in a single graph. In the tornadodiagrams, each bar represents a single one-way sensi-tivity analysis, and the legend provides details of eachof the analyses depicted. The variables are ranked bytheir effect on the overall radiotherapy utilization es-timate, with the variables that have most impact ap-pearing at the top of the graph and those with smallerimpact appearing below. Figure 2 shows that the pro-portion of patients with carcinoma of the head andneck who should receive radiotherapy based on evi-dence and incidence of attributes for radiotherapy is74% (the dashed line) and within the range of 73– 81%,

FIGURE 2. Tornado analysis of the variation in data and uncertainty in

evidence for radiotherapy in patients with head and neck carcinoma. Blue:

proportion of patients with Stage I–II carcinoma of the oral cavity undergoing

surgery (0.0–0.9); green: proportion of patients with operable carcinoma of the

lip (0.75–0.94); orange: proportion of patients with supraglottic laryngeal

carcinoma suitable for preservation surgery (0.0–0.16); gray: proportion of

patients with early-stage glottic carcinoma for whom radiotherapy is an

alternative; white: proportion of patients with unknown primary head and neck

tumors who have lymph node disease that does not warrant routine radiother-

apy (0.09–0.10). A description of the interpretation of the tornado diagram is

provided in the text (see Sensitivity Analysis).

RT Utilization in Head and Neck Carcinoma/Delaney et al. 2223

allowing for these uncertainties in sensitivity analysis.In some of the radiotherapy utilization reports that wepublished previously on other disease sites, a Monte-Carlo analysis was performed in which each of thevariables used in the sensitivity analysis were variedsimultaneously.7,9,11,13 This was not possible for thehead and neck tree, because not all of the sensitivityanalyses were for data variation, and many analyseswere based on modeling between two treatment alter-natives, such as surgery versus radiotherapy.

DISCUSSIONIn this study, we found that, optimally, 74% of allpatients with head and neck carcinoma (includingunknown primary tumors and lip carcinoma) shouldreceive radiotherapy according to evidence-basedtreatment guidelines for head and neck carcinoma. Bytumor site, the recommended optimal radiotherapyrates were oral cavity, 74%; lip, 20%; larynx, 100%;oropharynx, 100%; hypopharynx, 100%; nasopharynx,100%; paranasal sinus, 100%; salivary gland, 87%; andmetastatic squamous cell carcinoma of the neck, 90%.There are several areas within the management ofhead and neck carcinoma that remain uncertain.However, sensitivity analysis has shown that theseuncertainties have little impact on the overall result.All radiotherapy recommendations quoted from evi-dence-based clinical guidelines were based on LevelIII and IV evidence, although there is Level II evidencethat radical chemoradiation is superior to radiother-apy alone for advanced laryngeal carcinoma.61

It is acknowledged that radiotherapy utilizationrates of 100% may be considered unachievable. How-ever, there are some tumor subsites in the head andneck where radiotherapy is the mainstay of treatmentfor all stages of disease (e.g., nasopharyngeal carci-noma), because it is superior in terms of outcome ormorbidity compared with the alternative treatments ofchemotherapy alone or surgery. In other tumor sub-sites, the optimal radiotherapy utilization rate of 100%does not necessarily mean that all patients are suitablefor radical radiotherapy. However, even in patientswith metastatic disease and relatively poor perfor-mance status, it is usual for patients to have symptomsattributable to the primary or regional disease thatwould justify a short course of palliative radiotherapy.Rare instances of patient refusal to undergo any formof therapy or when radiotherapy truly is not recom-mended are likely to represent � 1% of patients73 and,hence, are unlikely to have a significant impact on theoverall optimal utilization rate of 100% for that sub-site. Actual radiotherapy utilization rates from Swedenin 20004 have shown that utilization rates of 100%, infact, are achievable in clinical practice.

Comparison with Actual PracticeThe optimal rates for each head and neck tumor sitewere compared with international data from the Sur-veillance, Epidemiology, and End Results (SEER) database,73 the South Australian Cancer Registry,41 theSwedish Radiotherapy Utilization Survey,4 and theYorkshire Cancer Registry.74 Two periods were exam-ined in the SEER data base. The periods chosen werethe most recent for which data were available (1995–2000) and 20 years prior (1975–1980) to evaluatechanges in actual utilization within a single study pop-ulation over time. Table 3 shows that radiotherapyutilization rates in South Australia, the United States,and Yorkshire were lower than optimal rates. Therewere some data to suggest an increased use of radio-therapy over time according to the SEER data (e.g., insalivary gland carcinoma, there was an � 16% increasein use over 20 years). However, there also were de-creases in the use of radiotherapy for nasopharyngealcarcinoma and hypopharyngeal carcinoma over thepast 20 years. The reasons for these reductions in usecould not be identified.

The data on actual utilization of radiotherapyshow that some tumor subsites have a reasonablecorrelation between actual and optimal radiotherapyrates (e.g., actual radiotherapy utilization rates in Swe-den are very close to the optimal rates for carcinomasof the nasopharynx, hypopharynx, larynx, and parana-sal sinuses). However, significant shortfalls also wereidentified for some populations. There are large dif-ferences between the SEER actual radiotherapy utili-zation rates versus the optimal rates for salivary glandtumors and tumors of the hypopharynx. Reasons forthese differences are not available. Some differencesmay be due to differences in stage distribution andhistologic subtype distribution in differing popula-tions, but it is unlikely that the differences solely relateto differing disease presentation. It is possible that realshortfalls exist in radiotherapy treatment delivery, andthis may reflect differences in opinion regarding therole of radiotherapy. This underlines the need forgood-quality, high-level (Level I–II) evidence for therole of radiotherapy. Unfortunately, most of the evi-dence is of poorer quality.

Actual rates of head and neck radiotherapy fromSweden in 20004 showed that actual and optimal rateswere identical for the types of head and neck tumorsfor which 100% of tumors should receive radiation(larynx, nasopharynx, oropharynx, paranasal sinuses)and showed that, for some tumor subsites, a 100% rateis achievable. For patients with oral cavity tumors inSweden, the actual rate of utilization was higher thanthe optimal rate, although the actual rate included

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brachytherapy, which appears to be more prevalentthan surgery in the management of oral cavity carci-nomas in Sweden. We may have underestimated theoptimal radiotherapy utilization rate for oral cavity tu-mors because of a lack of evidence for the superiority ofeither surgery or radiotherapy as primary treatment.

A survey of radiotherapy departments in NewSouth Wales (NSW), Australia,75 assessed the totalnumber of patients with head and neck carcinoma(excluding lip carcinoma and unknown primary tu-mors) who received radiotherapy in 2000. The datawere not separated by subsite location, and the actualradiotherapy utilization rate reported was 86%. Theoptimal rate for the same cohort of patients with headand neck carcinoma (i.e. excluding lip carcinoma andunknown primary tumors), as calculated by using thehead and neck radiotherapy utilization tree, was 89%.This close correlation between actual and optimal ra-diotherapy utilization for patients with head and neckcarcinoma in NSW is in stark contrast to most othertumor sites, for which we have reported larger discrep-ancies between actual rates and optimal rates.7,9,11,13–15

Possible reasons why the actual rates are similar to theoptimal rates in head and neck carcinoma may in-clude that patients with head and neck carcinoma inNSW generally are treated in specialist units (as op-posed to other types of carcinoma, for which care isdistributed more widely among clinicians), the highuse and proven efficacy of radiotherapy in head andneck carcinoma, and the existence of well acceptedevidence on the use of radiotherapy for head and neck

carcinoma, even though some of the evidence is notrandomized. Further study into the reasons behindthe convergence of optimal and actual radiotherapyutilization rates in head and neck carcinoma may helpto improve the gap between actual and optimal radio-therapy utilization rates for other tumor sites.

In conclusion, for this study, we used an evidence-based method to estimate the optimal radiotherapyutilization rate for head and neck malignancies. Therecommended proportion of all patients with headand neck carcinoma who, according to the best avail-able evidence, should receive at least 1 course of ra-diotherapy is 74%. This optimal utilization rate is sub-stantially higher than current practice in SouthAustralia and the United States, although it is similarto current practice in Sweden and to the practice in2000 in NSW. We believe that further epidemiologicalpatterns-of-care studies on the use of radiotherapy forpatients with head and neck malignancies are re-quired.

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TABLE 3Comparison of Optimal and Actual Radiotherapy Utilization Rates

Head and neck tumor subsiteOptimal RTutilization rates (%)

Actual RT utilization rates (%)

Sweden, 2002(Moller et al., 20034)

SA State CancerRegistry (Australia)1990–1994(Luke et al., 200341)

North Yorkshire(UK) 1999(NYCRIS, 199974)

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