Journal of Medical Imaging and Radiation Oncology  (2020) –

RADIATION ONCOLOGY—ORIGINAL ARTICLE

Influence of remoteness of residence on timeliness of diagnosis

and treatment of oral cavity and oropharynx cancer: A

Journal of Medical Imaging and Radiation Oncology

retrospective cohort study
Rebecca L Venchiarutti,1,2 Jonathan R Clark,1,3,4 Carsten E Palme,1,3,4 Thomas P Shakespare,5
Jacques Hill, Abdul Rahim Mohd Tahir,6 Patrick Dwyer1,7 and Jane M Young1,2,3
5

1 Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
2 Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital and the University of Sydney, Sydney, New South Wales, Australia
3 RPA Institute of Academic Surgery, Sydney Local Health District, Sydney, New South Wales, Australia
4 Sydney Head and Neck Cancer Institute, Chris O’Brien Lifehouse, Sydney, New South Wales, Australia
5 Department of Radiation Oncology, Mid North Coast Cancer Institute, Port Macquarie, New South Wales, Australia
6 Department of Radiation Oncology, Mid North Coast Cancer Institute, Coffs Harbour, New South Wales, Australia
7 Department of Radiation Oncology, Northern NSW Cancer Institute, Lismore, New South Wales, Australia

RL Venchiarutti BSc, MNutrDiet; JR Clark Abstract

MBBS (Hons Class 1), BSc(Med), MBiostat,
FRACS; CE Palme MBBS, FRACS;
TP Shakespare MBBS, MPH, GradDipMed
(ClinEpi), FAMS, FRANZCR; J Hill MBBS
FRANZCR; ARM Tahir MBBS FRANZCR;
P Dwyer BSc, MBBS FRANZCR; JM Young
MBBS, MPH, PhD, FAFPHM.
Correspondence
Ms. Rebecca L Venchiarutti, Surgical
Outcomes Research Centre (SOuRCe), Level 9,
Building 89, Royal Prince Alfred Hospital,
Missenden Road, Sydney, NSW 2050,
Australia.
Email:
Rebecca.Venchiarutti@health.nsw.gov.au
Conflict of interest: We disclose no conflicts of
interest.
Submitted 2 July 2019; accepted 29 October
2019.
doi:10.1111/1754-9485.12990
Introduction: Geographic disparities in head and neck cancer (HNC) outcomes
in Australia may be mediated by timeliness of diagnosis and treatment. This
retrospective cohort study examines geographic variations in survival and
time intervals leading up to treatment for HNC at two tertiary referral centres
in New South Wales.
Methods: Eligible patients were NSW residents aged ≥18 years, diagnosed with
primary oropharynx or oral cavity squamous cell carcinoma (SCC) between 01
July 2008 and 30 June 2013, and treated with curative intent. Main outcomes
were times from diagnosis to treatment and from surgery to post-operative
radiotherapy and overall survival. Differences based on remoteness of resi-
dence (regional/remote or metropolitan) were assessed.
Results: A total of 224 patients were eligible. Median time from symptom onset
to treatment was longer for regional/remote patients with oropharynx SCC
(4.7 vs. 3.8 months, P = 0.044) and oral cavity SCC (6.4 vs. 3.3 months,
P = 0.003). Median time from diagnosis to treatment was longer for regional/
remote patients with oropharyngeal SCC (47 days vs. 36 days, P = 0.003).
Time from surgery to adjuvant radiotherapy was longer among regional/re-
mote patients with oral cavity SCC (66 vs. 42 days, P = 0.001). Overall
survival did not differ based on remoteness.
Conclusion: Regional/remote HNC patients experienced longer times to diag-
nosis and treatment, and regardless of remoteness of residence, fewer than
half of patients were treated within guideline recommended timeframes.
Despite this non-adherence to guidelines, there were no differences in sur-
vival outcomes among this cohort. However, the impact of not meeting
guidelines on patient outcomes other than survival warrants further
investigation.

Key words: delivery of healthcare; geography; head and neck neoplasms; radi-
ation oncology; surgical oncology.

may be caused by both patient (demographic, geographic

Introduction and psychosocial issues) and health system factors, such
Pathways to treatment of cancer are complex and rarely as accessibility, policy and delivery.1 Minimising time
linear. Barriers to timely diagnosis and treatment of cancer between symptom onset and treatment is important, as

© 2020 The Royal Australian and New Zealand College of Radiologists 1

RL Venchiarutti et al.
delayed cancer diagnosis may increase risk of disease pro-
gression, recurrence and mortality, and more complex and
costly treatments with greater morbidity.2
In Australia, geographic variations in cancer outcomes
have been observed for several cancers,3 and despite
improving cancer survival rates, socio-economic and
geographic disparities persist.4,5 Variation in awareness
and uptake of screening practices may contribute to
these disparities. However, for rare cancers such as head
and neck cancer (HNC), for which there is no formal
screening programme, variations in cancer treatment
and access to care are postulated as major reasons for
observed outcome disparities.3 HNC is a heterogenous
term, representing over 10 different anatomical sites and
multiple histological types.6 In the context of non-speci-
fic signs and symptoms such as neck lumps, mouth
ulcers, hoarseness, otalgia or unintentional weight loss,
symptom appraisal can be difficult, potentially leading to
delays in diagnosis and treatment.
The 2016 Optimal Care Pathways for Patients with
Head and Neck Cancer (OCP-HNC)7 promotes access to
timely consultations and treatment to reduce patient
distress and reduce unwarranted clinical practice varia-
tion. One Australian study has investigated pathways to
treatment of HNC patients8 and the impact on survival
outcomes, reporting that patients living in remote/very
remote North Queensland had longer times to diagnosis
and treatment, and higher rates of recurrence compared
with those in regional North Queensland, though there
were no differences in survival. No study has investi-
gated these pathways in NSW or compared the path-
ways of regional/remote patients against metropolitan
patients. In this study, time intervals along the pathway
to treatment of HNC are quantified and compared with
OCP-HNC timeframes, and survival based on remote-
ness of residence and time from symptom onset to
treatment is examined.
Methods
An audit was conducted at the Head and Neck Service at
the Royal Prince Alfred Hospital (RPAH)/Chris O’Brien
Lifehouse (COBLH) in Sydney, and the Mid North Coast
Cancer Institute (MNCCI) in Port Macquarie and Coffs
Harbour, representing major HNC referral centres in
metropolitan and regional NSW. Eligible patients were
NSW residents aged ≥18 years, diagnosed with malig-
nant squamous cell carcinoma (SCC) of the oral cavity or
oropharynx from 01/07/2008 to 30/06/2013 and treated
with curative intent. Approval was granted by the Sydney
Local Health District Human Research Ethics Committee
(Protocol No X17-0393 & HREC/17/RPAH/589) and the
Aboriginal Health and Medical Research Council Human
Research Ethics Committee (Reference Number 1356/
17). Clinical governance approvals were approved by
each site, and a waiver of informed consent was granted.
2 © 2020 The Royal Australian and New Zealand College of Radiologists
Data sources and collection
Methodology was guided by the Aarhus Statement9 for
studies of cancer diagnosis pathways, which has been
used in studies conducted by the International Cancer
Benchmarking Partnership (ICBP) investigating variations
in cancer survival.10 Consecutive patients treated at the
Head and Neck Cancer Services at the RPAH/COBLH
were identified using a database at the Sydney Head and
Neck Cancer Institute. Data were collected from the elec-
tronic medical record, clinical oncology database (ARIAâ
Oncology) and specialists’ records. Consecutive patients
treated at the MNCCI were identified using the clinical
oncology database (MOSAIQTM), from which all data were
collected. These data sources ensured maximal sampling
coverage and completeness of information. Data were
collected using a standardised data collection form and
managed using the Research Electronic Data Capture
(REDCap) tool.11
Study variables and outcomes
Demographics
Demographic variables included gender, age at diagnosis,
country of birth, marital status and health insurance.
Socio-economic measures were obtained from the Aus-
tralian Bureau of Statistics (ABS) by geocoding patients’
residential addresses and associating addresses with a
Statistical Area Level 2 (SA2) in the Australian Statistical
Geography Standard.12 Each patient was assigned a
value for the four measures of socio-economic status
using the Socio-Economic Indexes for Areas (SEIFA,
2011 version)13 based on the SA2 corresponding to their
residence, with a lower values representing higher disad-
vantage.
Geographic variables
Remoteness of residence was derived from the patients’
SA2, coded according to the Accessibility/Remoteness
Index of Australia14 (ARIA+), then dichotomised into
metropolitan or regional/remote. For comparison against
the OCP-HNC, patients were grouped as follows: (i) lived
and treated in metropolitan NSW, (ii) lived in regional
NSW and treated in metropolitan NSW or (iii) lived and
treated in regional NSW for each component of
treatment.
Clinical and outcome data
Clinical data included tumour site, dates and types of
symptoms and investigations, and visits to primary and
secondary care. Comorbid conditions were scored
according to the methods of Charlson15 to obtain a single
score. Disease stage was defined using the TNM
 Geographic variation in times to HNC treatment

Classification of Malignant Tumours, 7th edition16 from decision to treat was not able to be reliably collected ret-
pathology reports or when unavailable, from clinical rospectively. As this would result in a longer interval than
stage. Survival data (dates of last follow-up and where if date of decision to treat had been used, the proportion
applicable, date of death) were collected from hospital or of patients commencing of treatment at 6 and 8 weeks
specialist records. since diagnosis in addition to the recommended 4 weeks
from decision to treat in the OPC-HNC was assessed. For
consistency, the proportion commencing adjuvant radio-
Definitions of time points and calculation of
therapy within 8 and 10 weeks of surgery in addition to
time intervals
the recommended 6-week interval was analysed.
Definitions for time points and time intervals (Table 1)
were derived from the Aarhus Statement9 and others
Statistical analysis
models of pathways to treatment.1,9 Diagnosis date was
assigned in a hierarchical method from the European Continuous variables are presented using means and
Network of Cancer Registries,9 with first priority given to standard deviations, or median and interquartile range
histopathological diagnosis, then cytopathological diag- (IQR). Between-group comparisons were conducted
nosis, imaging and date of first outpatient consultation using independent two-sample t tests or the Kruskal–
for the malignancy. In lieu of exact dates, ‘pseudoexact’ Wallis test for continuous variables and v2 tests for cate-
dates were derived using published methods.17 To make gorical variables with Fisher’s exact test. Adjusted sur-
comparisons against the OCP-HNC, date of decision to vival analyses were conducted using the Cox regression
treat was substituted with date of diagnosis, as date of method. Variables demonstrating P ≤ 0.25 on univariable
analysis and the explanatory variables of interest (re-
Table 1. Definitions of key time points and time intervals moteness of residence and total interval) were entered
into the full model alongside known predictors of sur-
Time point Definition
vival, and 95% confidence intervals were constructed
First symptom Date a patient first noticed a bodily change that around the hazard ratio (HR). The proportionality of haz-
prompted them to seek help from a health care ards assumption was tested by graphically assessing
practitioner Schoenfeld residuals. P-values were two-tailed and sta-
First presentation Date the patient first visited a health care tistical significance taken at P < 0.05. Statistical analyses
practitioner in primary or secondary care were conducted using IBM SPSS for Windows version
because of a bodily change 24.0 (IBM Corp, Armonk, NY, USA) and SAS software
First referral to Date of referral to a head and neck cancer
(Version 9.4 of the SAS system for Windows; SAS
secondary care specialist that took responsibility for diagnosis/
Institute Inc., Cary, NC, USA).
treatment
First specialist visit Date of first visit to a head and neck cancer
specialist that took responsibility for diagnosis/ Results
treatment
Diagnosis Date of definitive diagnosis of head and neck Two-hundred and twenty-four patients were eligible, 140
cancer malignancy from metropolitan NSW and 84 from regional/remote
Treatment onset Date of first occurring surgery, radiotherapy NSW. Patient characteristics are described in Table 2. All
fraction or chemotherapy dose for treatment of patients living in metropolitan NSW received treatment
the malignancy at the RPAH/COBLH Head and Neck Cancer Service. Of
Adjuvant therapy Date of first post-operative radiotherapy fraction
the 84 patients living in regional/remote NSW, 32 (38%)
onset
received all treatment in metropolitan NSW, 32 (38%)
Time interval Definition received all treatment in regional NSW and 20 (24%)
Patient interval Time from first symptom to first presentation
received treatment in both metropolitan and regional
Primary care interval Time from first presentation to referral to NSW.
secondary care
Diagnostic interval Time from first presentation to diagnosis
Time intervals
Treatment interval Time from diagnosis to treatment onset
Symptom to diagnosis Time from first symptom to diagnosis
interval Oropharynx
Referral to specialist Time from date of referral to specialist to first There were 112 patients with oropharyngeal cancer
visit specialist visit
included (65 metropolitan, 47 regional/remote). Med-
Specialist visit to Time from first specialist visit to treatment
ian time from diagnosis to treatment was longer for
treatment onset
Total interval Time from first symptom to treatment onset
regional/remote patients (47 days [IQR 43 days])
Adjuvant therapy Time from surgery to adjuvant therapy onset compared with metropolitan patients (36 days [IQR
interval 14 days]) (P = 0.003) (Table 3). Total time from
symptom onset to commencement of treatment was

© 2020 The Royal Australian and New Zealand College of Radiologists 3

RL Venchiarutti et al.

Table 2. Patient characteristics

Oropharynx Oral cavity

Metro (n = 65) Regional (n = 47) Total (n = 112) P Metro (n = 75) Regional (n = 37) Total (n = 112) P
Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD)

Age (years) 59.8 (11.9) 59.4 (9.7) 59.6 (11.0) 0.83 62.8 (13.5) 61.3 (12.2) 62.3 (13.1) 0.56
Socio-economic status
IRSAD (SD) 1044 (59) 936 (42) 999 (75) <0.001 1015 (71) 932 (49) 988 (75) <0.001
IRSD (SD) 1029 (53) 944 (43) 993 (65) <0.001 1002 (70) 942 (48) 982 (69) <0.001
IER (SD) 986 (60) 960 (38) 975 (54) 0.005 986 (64) 956 (40) 976 (59) 0.002
IEO (SD) 1089 (77) 940 (42) 1026 (98) <0.001 1041 (84) 935 (48) 1006 (993) <0.001

N (%) N (%) N (%) N (%) N (%) N (%)

Gender
Male 55 (85) 36 (77) 91 (81) 0.28 48 (64) 23 (62) 71 (63) 0.85
Female 10 (15) 11 (23) 21 (19) 27 (36) 14 (38) 41 (37)
Marital status
Married/de-facto 32 (49) 30 (64) 62 (55) 0.13 37 (49) 19 (51) 56 (50) 0.84
Single/widowed/divorced 33 (51) 17 (36) 50 (45) 38 (51) 18 (49) 56 (50)
Health insurance
No cover 50 (77) 43 (92) 93 (83) 0.043 53 (71) 28 (76) 81 (72) 0.58
Health cover or DVA card 15 (23) 4 (8) 19 (17) 22 (29) 9 (24) 31 (28)
Charlson Comorbidity Index
None (0) 34 (52) 32 (68) 66 (59) 0.25 34 (45) 13 (35) 47 (42) 0.60
Low (1–2) 21 (32) 10 (21) 31 (28) 28 (37) 18 (49) 46 (41)
High (3+) 10 (15) 5 (11) 15 (13) 12 (16) 6 (16) 18 (16)
Missing 1 (1) – 1 (1)
Stage
Early 9 (14) 5 (11) 14 (13) 0.55† 34 (45) 14 (38) 48 (43) 0.45
Advanced 56 (86) 41 (87) 97 (87) 41 (55) 23 (62) 64 (57)
Missing – 1 (2) 1 (1)
Treatment
Surgery only 2 (3) 1 (2) 3 (3) 0.86† 42 (56) 11 (30) 53 (47) 0.002†
Radiotherapy (RT) only 12 (19) 7 (15) 19 (17) – 3 (8) 3 (3)
Surgery + RT 3 (5) 1 (2) 4 (4) 24 (32) 20 (54) 44 (39)
Chemoradiotherapy (CRT) 45 (69) 37 (79) 82 (73) – 1 (3) 1 (1)
Surgery + CRT 3 (5) 1 (2) 4 (4) 9 (12) 2 (5) 11 (10)
Aboriginality
Aboriginal 1 (2) 3 (6) 4 (4) 0.31† – 3 (8) 3 (3) 0.034†
Non-Aboriginal 63 (97) 44 (94) 107 (96) 75 (100) 34 (92) 109 (97)
Missing 1 (2) – 1 (1) – – –

P-values in bold indicate P < 0.05.

†Fisher’s exact test. Percentages may not total 100 due to rounding. CRT, chemoradiotherapy; CT, chemotherapy; DVA, Department of Veteran’s
Affairs; IEO, Index of Education and Occupation; IER, Index of Economic Resources; IQR, interquartile range; IRSAD, Index of Relative Socio-Eco-
nomic Advantage and Disadvantage; IRSD, Index of Relative Socio-Economic Advantage; RT, radiotherapy; SD, standard deviation.

longer among regional/remote patients (median based on remoteness of residence in time from diagno-
4.7 months [IQR 3.4 months]) compared with sis to treatment regional/remote patients (regional/re-
metropolitan patients (median 3.8 months [IQR mote median 33 days vs. metropolitan median
3.9 months]) (P = 0.044). 29 days, P = 0.19). Total time from symptom onset to
treatment was significantly longer among regional/re-
mote patients compared with metropolitan patients
Oral cavity
(median 6.4 months [IQR 9.8 months] and 3.3 months
There were 112 patients with oral cancer (75 [IQR 4.0 months], respectively) (P = 0.003). Fifty-five
metropolitan, 37 regional/remote). Regional/remote patients underwent post-operative radiotherapy; of the
patients had a longer interval from symptom onset to 53 patients with complete treatment dates, the median
diagnosis (median 5.4 months [IQR 9.2 months]) com- interval between surgery and radiotherapy for regional/
pared with metropolitan patients (median 2.1 months remote patients was 66 days (IQR 24) and 42 days
[IQR 4.3 months]) (P = 0.002). There was no difference (IQR 9) for metropolitan patients (P = 0.001).

4 © 2020 The Royal Australian and New Zealand College of Radiologists

 Geographic variation in times to HNC treatment

Table 3. Time intervals along the pathway to diagnosis and treatment of oral cancer based on remoteness of residence

Oropharynx Metropolitan (n = 65) Regional/remote (n = 47) P†

N (%) Mean (SD) Median (IQR) N (%) Mean (SD) Median (IQR)

Patient interval (months) 20 (31) 3.8 (7.1) 1.3 (3.3) 8 (17) 3.5 (3.2) 2.8 (4.7) 0.35
Primary care interval (months) 18 (28) 2.0 (3.2) 0.8 (2.0) 6 (13) 1.2 (1.1) 1.1 (2.0) 0.97
Diagnostic interval (months) 21 (32) 2.7 (3.5) 1.1 (3.2) 8 (17) 1.5 (1.7) 1.1 (1.2) 0.68
Treatment interval (days) 65 (100) 41 (49) 36 (14) 47 (100) 45 (24) 47 (43) 0.003
Symptom to diagnosis interval (months) 60 (92) 5.6 (10.4) 2.6 (3.8) 43 (92) 5.0 (5.2) 3.6 (3.4) 0.26
Referral to specialist visit (days) 45 (69) 6 (8) 4 (6) 36 (75) 10 (11) 7 (8) 0.001
Specialist visit to treatment onset (months) 64 (99) 1.3 (1.6) 1.1 (0.7) 46 (98) 1.3 (0.7) 1.2 (1.0) 0.30
Adjuvant therapy interval (days)‡ 5 (83) 59 (21) 53 (30) 2 (100) 44 (17) 44 (24) 0.57
Total interval (months) 60 (92) 6.9 (10.6) 3.8 (3.9) 43 (92) 6.7 (5.5) 4.7 (3.4) 0.044

Oral cavity Metropolitan (n = 75) Regional (n = 37) P†

N (%) Mean (SD) Median (IQR) N (%) Mean (SD) Median (IQR)

Patient interval (months) 8 (11) 3.4 (5.1) 0.9 (5.4) 2 (5) 5.3 (3.4) 5.3 (4.8§) 0.40
Primary care interval (months) 6 (8) 1.9 (3.7) 0.4 (2.9) 1 (3) – – 0.86
Diagnostic interval (months) 9 (12) 1.6 (2.9) 0.6 (1.4) 2 (5) 0.2 (0.2) 0.2 (0.3§) 0.44
Treatment interval (days) 73 (97) 34 (33) 29 (21) 37 (100) 45 (57) 33 (21) 0.19
Symptom to diagnosis interval (months) 63 (84) 4.5 (6.6) 2.1 (4.3) 29 (78) 8.3 (8.4) 5.4 (9.2) 0.002
Referral to specialist visit (days) 54 (72) 8 (8) 5 (9) 20 (54) 10 (15) 6 (10) 0.88
Specialist visit to treatment onset (months) 68 (91) 1.0 (1.0) 0.8 (0.6) 30 (81) 0.9 (0.6) 0.8 (0.7) 0.66
Adjuvant therapy interval (days)‡ 33 (100) 47 (15) 42 (9) 20 (91) 67 (25) 66 (24) 0.001
Total interval (months) 63 (84) 5.7 (6.8) 3.3 (4.0) 29 (78) 9.5 (8.4) 6.4 (9.8) 0.003

†Mann–Whitney U test.
‡Denominator is number of patients who underwent post-operative chemo/radiotherapy. IQR, interquartile range.
§Range.
P-values in bold indicate P < 0.05.

(n = 16) of patients living and treated in metropolitan

Stage at diagnosis
There was no association between tumour stage and
remoteness of residence; 33% (n = 27) of regional/re-
mote patients with T3/4 disease compared with 36%
(n = 50) of metropolitan patients (P = 0.65) (n = 3
patients missing T-stage). There was no statistical evi-
dence of an association between nodal stage and
remoteness of residence (P = 0.15) with 59% (n = 82) of
metropolitan patients and 69% (n = 57) of regional/re-
mote patients with nodal disease at diagnosis (n = 2
patients missing N-stage).
Comparison to optimal care pathways
Surgery
All patients received surgery in a metropolitan hospital.
There were no differences in the proportion of patients
undergoing surgery within four weeks of diagnosis based
on remoteness of residence (Fig. 1a).
Definitive radiotherapy  chemotherapy
Fifteen per cent of patients living and treated regionally
commenced definitive radiotherapy (chemotherapy)
within four weeks of diagnosis, compared with 29%
NSW (Fig. 1b). At eight weeks since diagnosis, 97%
(n = 70) of patients treated in metropolitan NSW had
commenced radiotherapy, compared with 40% (n = 13)
of those living and treated regionally.
Adjuvant radiotherapy  chemotherapy
Of patients living and receiving radiotherapy regionally,
14% (n = 3) commenced radiotherapy within the recom-
mended six weeks from surgery, compared with 51%
(n = 26) of patients undergoing radiotherapy at a
metropolitan site (P = 0.018) (Fig. 1c). Within 10 weeks
of surgery, 92% (n = 36) of patients treated at a
metropolitan site had commenced radiotherapy, com-
pared with 67% (n = 14) of those living and treated in
regional NSW.
Rates of loco-regional and distant failure
There were no statistically significant differences in rates
of loco-regional or distant failure based on remoteness of
residence. The proportion of loco-regional failure was
slightly higher among patients living in metropolitan
NSW at 22.9% (n = 32) compared with patients living in
regional/remote NSW at 15.5% (n = 13) (P = 0.18). The
rates of distant failure were slightly higher among

© 2020 The Royal Australian and New Zealand College of Radiologists 5

RL Venchiarutti et al.
Fig. 1. Proportion of cases meeting guidelines in the optimal care pathways for patients with head and neck cancer.
patients living in regional/remote NSW (10.7%; n = 9)
compared with those living in metropolitan NSW (7.9%;
n = 11) (P = 0.47).
Survival
Mean survival was 6.8 years (95% CI 6.1, 7.6) and
7.6 years (95% CI 3.9, 8.2) for patients living in regio-
nal/remote and metropolitan NSW, respectively (log-rank
P = 0.66; median survival estimates not reached). Multi-
variable modelling showed no difference in overall sur-
vival (HR 1.33 [95% CI 0.66, 2.71], P = 0.43) based on
remoteness of residence, after adjusting for age, gender,
tumour site, stage, comorbidity, Indigenous status and
total interval (Table 4). There was evidence that a longer
total interval (above the median of 4 months) was asso-
ciated with better survival (HR 0.49 [95% CI 0.24,
1.00], P = 0.049).
Discussion
The major findings were that patients living in regional/
remote NSW experienced longer intervals to diagnosis
and treatment; however, this did not translate into any
compromise in survival, consistent with results published
by the included regional centres.18 While there appar-
ently was no difference between the time from diagnosis
6 © 2020 The Royal Australian and New Zealand College of Radiologists
to surgery based on geography, there are clear differ-
ences in times from symptom onset to diagnosis, diagno-
sis to commencement of definitive radiotherapy and
surgery to radiotherapy, which may be partly accounted
for by the complexity of HNC management. Most patients
undergo surgery in a dedicated metropolitan HNC ser-
vice, requiring multiple referrals between regional and
metropolitan specialists if diagnosis and post-operative
treatment occurs at a local cancer centre. Metropolitan
surgical and multidisciplinary teams often act as ‘gate-
keepers’ to referrals to regional departments, which may
account for the observed differences in times to diagno-
sis and treatment, favouring patients living in metropoli-
tan NSW. Further, many patients referred to regional
radiotherapy departments are often not ‘ready for care’.
Time from referral to commencement of RT may be
affected by unique requirements such as pre-treatment
dental extractions, insertion of gastrostomy feeding
tubes and integration with chemotherapy treatment. It is
possible that the low proportion of patients, regardless of
geography, meeting OCP-HNC recommendations for
radiotherapy commencement reflects this complexity,
indicating improvements for all patients could be made
in this area.
Our findings compare with previous Australian litera-
ture, particularly that increasing remoteness of residence
is associated with longer intervals to diagnosis and
 Geographic variation in times to HNC treatment

Table 4. Cox regression model for overall survival driven by tumour biology as well as symptom apprai-
sal.22 Though outside the scope of the present data, an
Characteristics Overall survival
analysis of competing risks using population-level data
Univariable Multivariable may add additional insight into the influence of time
intervals on survival among HNC patients.
HR [95% CI] P HR [95% CI] P
We found that there was no different in extent of dis-
Gender ease at presentation between groups, despite longer
Male 1.00 (ref) 1.00 (ref) intervals observed among regional/remote patients. This
Female 1.32 [0.71, 2.42] 0.38 1.08 [0.52, 2.24] 0.84 may be due to the combination of clinical and surgical
Age at diagnosis 1.02 [1.00, 1.05] 0.11 1.00 [0.97, 1.03] 0.93 staging used in this study, although surgical staging was
(years) prioritised over clinical staging when appropriate. In a
Tumour site study synthesising studies of diagnostic pathways on
Oropharynx SCC 1.00 (ref) 1.00 (ref)
various endpoints, Neal et al.2 found an equal number of
Oral cavity SCC 1.65 [0.93, 2.93] 0.09 1.69 [0.82, 3.45] 0.15
studies found no association between diagnostic delays
Stage
Early 1.00 (ref) 1.00 (ref)
and stage at diagnosis as there were that found an asso-
Advanced 1.34 [0.67, 2.69] 0.41 1.92 [0.78, 4.70] 0.15 ciation. A prospective study by Tan et al.8 also found no
Marital status difference in stage at diagnosis based on remoteness of
Single 1.00 (ref) – residence (though comparisons were only made between
Married/partner 0.97 [0.55, 1.71] 0.92 regional and remote patients), and Bergin et al.23 found
Comorbidity no difference in extent of disease at diagnosis among
None 1.00 (ref) 1.00 (ref) breast and colorectal cancer patients based on remote-
Low (1–2) 3.17 [1.57, 6.37] 0.001 1.68 [0.77, 3.70] 0.18 ness of residence (metropolitan or regional/remote). This
High (3+) 5.25 [2.39, 11.5] <0.001 3.75 [1.56, 9.01] 0.003
differs from historical data suggesting regional/remote
Health insurance
patients present with more advanced disease3 and so it
No 1.00 (ref) –
Yes 0.89 [0.44, 1.79] 0.75
may be a result of improved cancer pathways over the
Remoteness of residence last two decades. Further, there were no statistically sig-
Metropolitan 1.00 (ref) 1.00 (ref) nificant differences based on remoteness of residence in
Regional/remote 1.14 [0.64, 2.03] 0.66 1.33 [0.66, 2.71] 0.43 the rates of loco-regional or distant failure. Rates of loco-
Aboriginality regional failure were higher in metropolitan patients;
No 1.00 (ref) 1.00 (ref) however, rates of distant metastases were slightly higher
Yes 0.52 [0.07, 3.76] 0.52 1.18 [0.15, 9.16] 0.87 among regional/remote patients. It is possible that pro-
Total interval longed pre-treatment intervals may increase the risk of
≤4 months 1.00 (ref) 1.00 (ref)
distant failure; however, due to the small proportion
>4 months 0.49 [0.25, 0.94] 0.03 0.49 [0.24, 1.00] 0.049
of patients with distant failure, this analysis was not
P-values in bold indicate P < 0.05. conducted.
Our retrospective methods are the major study limita-
tion. Most dates and events along the pathway to treat-
treatment, but not overall survival.8 Recently, Flukes ment were collected from tertiary medical records and
et al.19 showed that 46% of HNC patients in Western recorded after diagnosis, which may have precipitated
Australia met the Australian benchmark of commencing recall bias, particularly for events leading up to presenta-
treatment within 56 days of referral to a specialist. In tion to secondary care, as knowledge of a cancer diagno-
our study, of the 164 patients for whom this interval was sis may have influenced patients’ recollection of events
able to be determined, 80% met this guideline. A higher and attribution to cancer.24 To minimise bias, data were
proportion of metropolitan patients (87.3%) met this cross-referenced from multiple sources and previously
guideline compared with regional/remote patients published methods were utilised to allocate diagnosis
(67.7%); however, it is positive that two-thirds of regio- dates9 or estimate17 other dates when unavailable. Vari-
nal patients met the benchmark. The present study ous definitions of delays and intervals have been sug-
demonstrated that a longer total interval (>4 months) gested, which vary by country or jurisdiction.25 We were
was associated with better survival, which though coun- unable to accurately ascertain time points such as ‘deci-
terintuitive is reflective of previous literature.2 In the sion to treat’ and derive intervals used in contemporary
Netherlands, HNC patients with treatment delay quality indicator reporting, from which we would be able
>30 days had better disease-specific survival than those to better pinpoint causes of delay. In the case of compar-
treated within 30 days.20 The authors further charac- ison to the OCP-HNC, this likely resulted in non-differen-
terised the non-linear association between survival and tial misclassification; however, an attempt to ameliorate
diagnostic delays, with the poorer outcomes observed in this bias was made by extending analysis to time periods
patients with the shortest and longest treatment inter- after those described in the OCP-HNC. Further, the find-
vals.21 In the HNC population, these associations may be ings represent two referral centres in NSW from 2008 to

© 2020 The Royal Australian and New Zealand College of Radiologists 7

RL Venchiarutti et al.
2013 and may not be representative of other centres.
Since the timeframe this study represents, significant
changes have occurred such as the addition of an addi-
tional linear accelerator at both Coffs Harbour and Port
Macquarie sites (for a total of two linear accelerators at
each site), and the opening of the radiation oncology
facility in Lismore in northern NSW. It is likely that great
gains in accessibility and timeliness of treatment have
been made at each of these sites since 2013, which will
be examined in a prospective cohort study currently
underway and compared with the present study. We
gave preference to surgical pathological staging in this
study; however, in some cases, this was unavailable,
resulting in a mixture of clinical and pathological staging.
While pathological nodal staging is superior in predicting
overall survival compared with clinical nodal staging,
there are no major differences between the two staging
systems for prognostication purposes.26 Though outside
the scope of the current study, information on salvage
treatment for cases of loco-regional failure could provide
further insight into diagnostic and treatment delays after
primary treatment and should be considered in future
studies. Further, this study was powered to detect differ-
ences in the treatment interval (diagnosis to treatment)
and so it is possible this study was underpowered to
detect survival differences.
The increasing number of studies investigating optimal
timeframes for diagnostic and treatment processes
raises the question of which (and whether) guidelines
should be updated, and if so, to what degree. Currently,
there are few international guidelines on timeliness of
components of the diagnosis and treatment pathway.
Guidelines relating to onset of treatment are the most
common, and one of the most frequently cited is that the
interval between surgery and commencement of adju-
vant radiotherapy should not exceed six weeks, which
has been published in Australian7 and international
guidelines.27–30 Cramer et al.31 identified this interval as
a clinically meaningful metric, with an interval within six
weeks associated with better overall survival. However,
only 44.5% of patients commenced radiotherapy within
this interval, which was one of the poorest adherence
rates among the six quality indicators examined and is
comparable to the rate in our series (38%). There is also
evidence that prolonged treatment package time (time
from surgery to end of radiotherapy) is associated with
poorer loco-regional control. Chao et al.32 demonstrated
that treatment package time >15 weeks was associated
with worse loco-regional control among but not survival
among HPV+ oropharyngeal cancer patients, and Goel
et al.33 demonstrated that treatment package time of
>14 weeks was shown to reduce survival. Tumati et al.34
demonstrated that a prolonged radiation treatment time
(≥43 days) is associated with associated with a greater
hazard of loco-regional recurrence among patients with
p16 negative oropharynx or SCC of the oral cavity, larynx
or hypopharynx.
8 © 2020 The Royal Australian and New Zealand College of Radiologists
However, these metrics would only be applicable to
patients with HNC who undergo surgery and adjuvant
radiotherapy. Additional intervals that apply to a greater
proportion of HNC patients should also be considered.
For example, Flukes et al.19 suggest a new metric of
referral (to a specialist) to biopsy. Such a metric encom-
passes several measures of health system efficiency
such as primary care referrals to specialists/secondary
care, wait times for specialist appointments and avail-
ability of operating theatres for biopsies that may be
unable to be conducted in clinics. However, these data
would need to be collected prospectively, as our series
showed only 70% patients could have the date of referral
to a specialist determined retrospectively. While the
above metrics have the benefit of being more easily and
accurately obtained, delays that occur in primary care
that are more difficult to measure may also impact the
outcomes. Therefore, a composite measure weighting
specific intervals along the diagnostic pathway may be
considered. However, larger studies using population-
based data should be performed to determine the appro-
priate weights given to each individual measure within
the composite.35
Reasons for observed variation in timeliness of diagno-
sis and treatment are multifactorial,36 likely involving
access to primary care, diagnostic and treatment ser-
vices, poor symptom appraisal and patient preference,
each of which are difficult to measure retrospectively and
objectively. Mixed methods studies are currently under-
way in which precise mapping of patient pathways from
symptom onset to commencement of treatment, which
will help to identify specific facilitators and barriers to
early diagnosis and treatment of HNC. These studies will
be critical to build an evidence base to effectively influ-
ence health policy and practice and develop interventions
to minimise clinical variation and potentially improve
outcomes for all HNC patients regardless of residence.
Acknowledgements
The authors wish to thank Mr Kan Gao at the Sydney
Head and Neck Cancer Institute and Ms Deanna Tune at
the Mid North Coast Cancer Institute (Coffs Harbour) for
their assistance in data extraction and identification of
patients. Ms Rebecca Venchiarutti received travel funding
from the Cancer Research Network at the University of
Sydney to attend the 2018 Australia and New Zealand
Head and Neck Cancer Society (ANZHNCS) Annual Sci-
entific Meeting (Melbourne) and was awarded a travel
grant from the Clinical Oncology Society of Australia
(COSA) to attend the 2018 COSA ASM in Perth to present
this research.
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