Oral Oncology 62 (2016) 4453

Contents lists available at ScienceDirect

Oral Oncology
journal homepage: www.elsevier.com/locate/oraloncology

Review

Assessing head and neck cancer patient preferences and expectations: A

systematic review
Pierre Blanchard a,e, Robert J. Volk b, Jolie Ringash f, Susan K. Peterson c, Katherine A. Hutcheson d,
Steven J. Frank a,
a
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
b
Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
c
Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
d
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
e
Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France
f
Department of Radiation Oncology and Otolaryngology-Head Neck Surgery, Princess Margaret Cancer Centre/UHN and the University of Toronto, Toronto, Canada

a r t i c l e i n f o a b s t r a c t

Article history: Introduction: To enhance the value of care, interventions should aim at improving endpoints that matter
Received 22 August 2016 to patients. The preferences of head and neck cancer patients regarding treatment outcomes are therefore
Received in revised form 20 September a major topic for patient-centered research.
2016
Methods: A systematic review (PROSPERO number CRD42016035692) was conducted by searching elec-
Accepted 23 September 2016
Available online 6 October 2016
tronic databases (Medline, Embase, Cochrane, CINAHL) for articles evaluating patient or surrogate pref-
erences in head and neck cancer. A qualitative review was performed but no quantitative synthesis.
Results: Of 817 references retrieved, 20 full-text articles were eventually included in the qualitative anal-
Keywords:
Head and neck cancer
ysis Disease sites included mixed head and neck tumor sites, n = 9; larynx, n = 6; oropharynx/oral cavity,
Oropharyngeal cancer n = 5. Overall, patients prioritized survival over functional endpoints. However, preferences and utility
Patient preference scores varied greatly between patients and healthy subjects, and differences were less pronounced with
Patient priority spouses or healthcare providers. Findings from studies of laryngeal preservation are consistent and con-
Decision regret clude that a subset of patients would be willing to compromise a certain amount of survival to avoid
Laryngectomy laryngectomy. On the other hand, studies of patients with oropharyngeal cancer are too heterogeneous
Systematic review to draw conclusions about acceptable functional trade-offs or priorities, and should be the focus of future
research.
Conclusion: Future research surrounding head and neck cancer patients will most likely be clinically
applicable if the questions are focused on well-defined patient groups and treatment options.
Gathering reliable and valid quality-of-life data, designing patient preference studies that use reliable
and generalizable methods, and using the results to develop decision aids for shared decision-making
strategies are recommended going forward.
2016 Elsevier Ltd. All rights reserved.

Introduction [3]. However, little attention has been given to head-and-neck

Outcomes of patients with head and neck cancer have gradually
improved over the past decades due to improved treatments and
epidemiologic shifts [1,2]. Patient-reported outcomes (PROs) are
increasingly collected more systematically in efforts to better
understand the patients perspectives on potential trade-offs
between the likely effectiveness of a treatment and its side effects
Corresponding author at: Department of Radiation Oncology, Unit 1422, The
University of Texas MD Anderson Cancer Center, 1400 Pressler St., Houston, TX
77030, USA.
E-mail address: sjfrank@mdanderson.org (S.J. Frank).
cancer patient preferences other than those related to laryngeal
preservation.
The evolution of radiotherapy techniques for the treatment of
head and neck cancer has considerably reduced late toxicity, espe-
cially the incidence and severity of late xerostomia, by using
parotid-sparing intensity-modulated radiotherapy (IMRT) [4].
Although the implementation of IMRT in the United States has
been rapid, no randomized trials have been conducted in the Uni-
ted States to systematically compare radiation therapy techniques
in terms of clinical outcomes or potential benefits. One barrier to
the conduct of these trials was the perception that the benefit
was obvious and that randomization was unethical. Other

http://dx.doi.org/10.1016/j.oraloncology.2016.09.008
1368-8375/ 2016 Elsevier Ltd. All rights reserved.
 P. Blanchard et al. / Oral Oncology 62 (2016) 4453
countries have successfully demonstrated clinical benefit for
patients with head and neck cancer: a small randomized controlled
trial (RCT) conducted in the United Kingdom [4], a second small
RCT from India [5,6], and three RCTs in nasopharyngeal cancer
patients conducted in China [79]. Only three of these trials inves-
tigated patient reported outcomes as secondary endpoints [4,5,8].
The next generation of treatments for head and neck cancers
includes new radiotherapy modalities, such as particle therapy,
and the renewed use of surgery in the form of transoral robotic sur-
gery (TORS). Initial reports indicate that particle therapy and TORS
seem to provide durable tumor control of oropharyngeal cancer
[10,11] with acceptable toxicity, but high-quality prospective, mul-
ticenter data are lacking. Although the authors of one retrospective
uncontrolled comparison suggest that TORS could produce better
functional outcomes than chemoradiation for oropharyngeal can-
cer [12], the respective values of new treatments relative to one
another and to more established approaches needs to be assessed
in a patient-centered manner.
Value in health care is currently defined as outcomes divided by
costs, measured over the entire cycle of care [13]. The outcomes to
be considered in the value framework have many components, and
choosing the ones that matter the most to patients is a challenge
[14]. Investigating patient preferences or priorities regarding treat-
ment outcomes is an essential part of quantifying the value associ-
ated with various forms of treatment. We conducted a systematic
review of the current evidence regarding the preferences and prior-
ities of patients with head and neck cancer. Our aims were to sum-
marize the current data, describe the knowledge gaps, and propose
ways to improve research on patient priorities and foster shared
decision-making between patients, caregivers, and providers.
Methods
Inclusion criteria and search
This systematic review was conducted in accordance with
published guidelines [15] and was registered in the PROSPERO
database (CRD42016035692). Pubmed, Medline, Embase, The
Cochrane Registry, and the Cumulative Index of Nursing and Allied
Health Literature (CINAHL) were searched for relevant articles.
Inclusion criteria were: peer-reviewed articles focused exclusively
on head and neck mucosal neoplasms (excluding esophageal and
thyroid cancers or lymphoma); limited to localized disease; and,
evaluated patient preferences/priorities or health utility by using
a quantitative method. Keywords used included patient
preference, patient priorities and head and neck cancers, as
well as variations on these keywords and the different patient
stated-preference methods [16], such as rating, ranking,
best-worst, self-explicated, value-based conjoint analysis,
rating-based conjoint analysis, choice-based conjoint analysis,
take it or leave it, tradeoff, and trade-off. The full search
equations used for the different databases are given in the Supple-
mentary Materials. No restrictions on date or study design were
applied. Review articles on outcomes-based research and value-
based research in head and neck cancer were searched for addi-
tional references, although this search did not retrieve any new ref-
erences. Abstracts and articles were assessed by one experienced
head and neck radiation oncologist (PB), and checked by a second
(SJF) and any disagreements were resolved by consensus.
Description of the studies included and methods used to assess patient
preferences
The PRISMA flow diagram is presented in Fig. 1. Our search
retrieved 817 references, including 238 duplicates and 81 confer-
45
ence proceedings; 442 references were excluded when analysis
of the abstract revealed their irrelevance to the present study
(major reasons: related to epidemiology/public health, reporting
on outcomes but not on patient preference, focused on other dis-
ease sites such as thyroid gland or esophagus, review articles,
and other reasons). Of the 56 full text articles evaluated, 36 were
excluded for the reasons shown in Fig. 1, leaving 20 references
for inclusion in the systematic review. The data collected for each
study were dates of accrual, type of participants included, treat-
ments studied, methods (instrument) used to assess preferences,
mode of delivery (e.g. face to face interview or mail), timing of
the assessment with respect to the delivery of treatment, and main
results or study biases.
Among the 20 references included, nine evaluated preferences
of patients with mixed head and neck cancer diagnoses, five
focused on oral cavity or oropharyngeal cancers, and six focused
on the issue of laryngeal preservation. Different stated-preference
methods were used, and sometimes several methods were used
in the same study. Two references were related to the same study
but reported different statistical analyses, and so were both
included [17,18]. The most commonly used methods were rank-
ing/rating (10 studies), time tradeoff (7 studies), and standard
gamble (2 studies). These methods are summarized briefly in
Table 1 and described further in the Johns Hopkins white paper
[16].
In terms of study participants, 13 studies involved patients
with head and neck cancer; 8 studies, healthy subjects; 5 studies,
caregivers or experts on head and neck cancer; 3 studies, patients
with head and neck or pulmonary conditions other than cancer;
and 1 study, spouses of patients with head and neck cancer.
Eleven studies evaluated preferences in more than one group of
participants. Regarding treatments, 12 studies were not compara-
tive and mostly ranked patient outcomes, 7 studies compared
preferences between surgery and radiotherapy, mostly with
regard to laryngeal preservation, and 3 studies evaluated prefer-
ences between radiotherapy and concomitant chemoradiation.
Nineteen studies were cross-sectional, and only one was longitu-
dinal [19]. No formal assessment of the quality of the studies
could be performed due to their design and the absence of an
appropriate scale. Similarly, no quantitative synthesis could be
performed owing to the heterogeneity of publication and type of
results reported.
Results
Characteristics of the studies analyzed, including date of con-
duct, type of participants, treatments used or compared, methods
of stated-preference assessment, timing with regard to treatment
for head and neck cancer patients, and main results, are shown
in Tables 24. Studies are grouped according to disease site: mixed
head and neck tumor sites (Table 2), oral cavity and oropharyngeal
cancers (Table 3), and laryngeal cancers (Table 4). Health states
considered and utility values are reported in Table 5 for the studies
that used such metrics. The major findings of these studies are
summarized below.
Superiority of survival over functional endpoints
In all of the studies in which survival/cure was one of the end-
points that patients had to rate or rank, being cured and surviving
consistently ranked at the top of the list [17,18,2022]. Although
this finding seems obvious, it nevertheless underscores the expec-
tation that high survival rates are a prerequisite of any treatment
that is being administered or is under development. Although in
some instances, some patients accept a certain degree of tradeoff
46 P. Blanchard et al. / Oral Oncology 62 (2016) 4453

Fig. 1. Trial search flow chart.

Table 1
Description of the main methods used for evaluating head and neck cancer patient preferences.

Name Description Example [reference]

Ranking/rating Researchers ask patients to rate a set of outcomes on an ordered
Likert-type scale (rating) or to rank them from the most to the least
important. Rating can also use visual analog scale and in this case
utilities can be derived
Time trade-off Researchers ask patients to choose between the health state as
described in a clinical scenario during X years, and a shorter life in
normal health. The duration X is varied until the patient is unable to
choose between the two options
Standard gamble Researchers ask patients to choose between two possible outcomes: a
suboptimal health state that is certain and a gamble with one better
(for example, full health) and one worse (for example, death) outcome
possible. The probability of the gamble is varied during the experiment
and the point of indifference is used to derive the utility of the health
state
From Ref. [17]: Patients are presented with [. . .] 12 positively phrased
statements [. . .]. They are asked to arrange the cards on the board into
three categories: highest priority, medium priority, and lower priority.
Patients are then instructed to rank order statements within each
category
From Ref. [27]: participants were offered a choice between alternative
1 (to remain in one of the health states for 10 years) and alternative 2
(to retain normal health, but with a decreased survival [x years]). X was
varied until the respondent became indifferent between the 2 alter-
natives, at which point the utility value for that health state was
derived
From ref [24]: In [. . .] the standard, subjects are given the option of
certain life in an intermediate or suboptimal health state [. . .]. In the
[. . .] gamble, subjects are given the option of taking an imaginary pill
that has a risk of sudden and painless death. If the pill is successful,
however, subjects would live in perfect health but with the same risk of
cancer recurrence as the first alternative. Subjects are asked to decide
between these 2 alternatives

between survival and side effects (which can be explored through Variability between patients and surrogates
the time tradeoff or standard gamble methods), in general,
patients will not trade large differences in survival for functional In 11 studies that investigated more than one participant
outcomes. group, especially 8 that included both head and neck cancer
Table 2
Description of studies that included patients with all types of head and neck tumors.

All tumors
Study [ref] Institution Date n Type of Treatments Methods Delivery Timinga Main results
participants (instrument)
Jalukar [23] University of 1998b 185 HNC pts (49) Not disease- TTO Patient form >12 mo after 1. Similar preference values between patients and professionals for HN-
Iowa, USA in the clinic trtmt specific domains (appearance, eating, speech, breathing) but not for
Providers (50) Or modality- Mail for the general domains (pain and work/social)
others 2. Major discordance between patients and students for all domains, with
Students (86) Specific lower utility values given by students than patients
Hodder [38] Cardiff, UK 1997 35 HNC pts Not specified Rating Face to face Not specified 1. Top outcomes were social function and pain
2. Followed by physical appearance, eating and speech problems
Sharp [20] University of 1998 43 HNC pts (20) Not disease- or Ranking (CPS, Face to face Before & 1 & 1. Being cured/live longer uniformly ranked first

P. Blanchard et al. / Oral Oncology 62 (2016) 4453

Chicago, USA Healthy modality- design of the 6 mo after 2. Important variations between patients, and healthy subjects
subjects (23) specific scale) trtmt 3. High variability between groups according to treatment time
List [17] & List [18] Chicago 1999 388 HNC pts (247) Not disease- or Ranking (CPS, Face to face Before trtmt 1. Cure ranked first for 75% of pts
(multi- 2004b Healthy modality- FACT-HN, PSS- 2. Then items related to living long, having no pain, energy, swallowing,
institution), subjects (131) specific HN) voice, and appearance, but considerable variability, unrelated to patient
USA or disease characteristics (except survival, which was rated slightly
lower by older pts)
3. No clear hierarchy regarding the other domains
4. No strong correlation between quality-of-life scores and priorities
Gill [21] Newcastle, UK 2007 85 HNC pts (30) Not disease- or Ranking (CPS, Face to face >6 mo after 1. Being cured/live longer uniformly ranked first
Spouses (30) modality- Ottawa DRS) trtmt 2. Pain and swallowing items ranked next, but with varying scores
Multidisc specific 3. No concordance for all 8 other items
team 4. Agreement between patients, spouses and multidisciplinary team
members (25) members regarding priorities
Kanatas [22] and Liverpool, UK 2011 447 HNC pts, Not disease- or Ranking (PCI, Mail 113 years 1. Fear of recurrence was the first concern
Rogers [39] & overlapping modality- UW-QoL) after trtmt 2. Dental health/teeth and chewing as general concern
483 cohorts specific 3. Followed by issues more specific to each disease: speech (larynx), sali-
vation (oropharynx)
4. Variation by pt age (less fear of recurrence in among elderly pts)
Tschiesner [40] Munich, 2010 300 300 HNC pts Not disease- or Ranking (ICF- Mail Most (79%) 1. Survival ranked first (but only by 58% of pts)
Germany (of 521 total modality- HNC) + handed >1 year after 2. All expenses for cancer treatment being covered 2nd (51%)
pts) specific out in clinic trtmt 3. Being able to continue performing all daily life tasks well (50%)
4. Significant differences by sex, tumor stage, and location

Abbreviations: CPS, Chicago Priority Scale; DRS, Decision Regret Scale; FACT-HN, Functional Assessment of Cancer Therapy-Head and Neck; HNC, head and neck cancer; ICF-HNC, International Classification of Functioning,
Disability and Health Core Set for Head and Neck Cancer; PSS-HN, Performance Status Scale for Head and Neck Cancer; PCI, patient concerns inventory; pts, patients; S, subject; TTO, Time Trade Off; trtmt, treatment; UW-QOL,
University of Washington Head and Neck Cancer Questionnaire.
a
Timing for patients only.
b
The date is year of publication, because survey dates were not reported.

47
 48
Table 3
Description of studies that included patients with oropharynx and oral cavity cancers.

Oropharynx and oral cavity cancers

Study [ref] Institution Date N Type of Treatments Methods Delivery Timinga Main results
participants
Rogers [19] Liverpool 1998 48 OC, OPC pts Surgery Ranking (UW- Questionnaire Before trtmt and 1. Patients tended to rate speech, chewing and swallowing as more
University, 1999 QOL) 6 & 12 mo after important
UK surgery 2. Wide variation in importance ratings between patients
3. But consistency from before to after treatment

P. Blanchard et al. / Oral Oncology 62 (2016) 4453

4. Lack of correlation between importance rating and domain scores
Brotherson [29] University 2010 51 OPC pts CRT, XRT TTO Face-to-face >3 mo after 1. 69% of pts would not trade CRT for XRT if the risk of death was
of Toronto, 2011 trtmt greater than 5%
Canada 2. Affected by patients rating of their own experience with toxic
effects
Murthy [30] Tata 2012 837 OC pts Three Reason for non- 1. Being treated closer to their home (26.2%)
Memorial adjuvant post- inclusion in 2. Lack of interest in clinical trial (16.8%)
Hospital, op trtmts clinical trial 3. Significant predictors of non-enrollment: sex (female), education
India status (illiterate), occupation (laborers), and unavailability of sup-
port system in the city
Govender [31] University 2013 10 OC/OPC pts with Surgery XRT Ranking (12- Face-to-face 412 mo after 1. No clear ranking of eating/talking symptoms apart from one that
College severe toxicity (active (1 w/CRT items scale trtmt has the least priority (eating as quickly as before)
London, UK rehabilitation) alone) designed) 2. Large variability depending on patients toxicity profile
De Almeida [24] Mount 2014b 59 Healthy subjects (50; TORS, CRT, VAS Face-to-face Not relevant Treatment ranking (best to worst VAS): TORS > TORS-
Sinai, New mean age 35y) XRT for healthy XRT > XRT  TORS-CRT > CRT
York, USA subjects
HNC experts (9) SG Group Toxicity ranking (worst to least): permanent gastrostomy, esophageal
meeting for stenosis, osteoradionecrosis, permanent tracheostomy,
experts pharyngocutaneous fistula, temporary gastrostomy

Abbreviations: CRT, chemoradiotherapy; HNC, head and neck cancer; OC, oral cavity cancer; OPC, oropharyngeal carcinoma; pts, patients; SG, standard gamble; TORS, transoral robotic surgery; TTO, Time Trade Off; trtmt,
treatment; UW-QOL, University of Washington Head and Neck Cancer Questionnaire; VAS, visual analog scale; XRT, radiotherapy.
a
Timing for patients only.
b
Date is year of publication, because survey dates were not reported.
Table 4
Description of studies that included patients with larynx/hypopharynx cancers.

Laryngeal preservation
Study [ref] Institution Date n Type of persons Treatments Methods Delivery Timinga Results
b
Mc Neil [26] MGH, Boston 1981 37 Healthy subjects (25) XRT vs TL TTO Face-to-face NR 1. Survival not the only priority for all patients
Firefighters (12) 2. On average, individuals would trade 14% of their life expectancy to maintain

P. Blanchard et al. / Oral Oncology 62 (2016) 4453

normal speech Utility of larynx preserving strategies is 86%
Otto [41] UT San 1997 59 TL pts (46) XRT vs TL TTO Face-to-face After trtmt 1. Only 20% of pts willing to trade survival for function, by a mean of 5.6 years
Antonio HNC clinicians (13)
Van der Donk [25] Rotterdam, 1995 39 Lx cancer pts (10) XRT vs TL TTO, SG, Face-to-face >3 years 1. Considerable differences in utilities between respondent groups and assessment
Netherlands Floor of mouth cancer RS, DC after trtmt methods
pts (10) 2. Most respondents preferred XRT; utilities always higher for XRT than TL
HNC clinicians (9)
Healthy subjects (10)
Laccourreye [28,42] Paris, France 2010 309 General HN pts (87% XRT vs TL TTO Questionnaire NR 1. 28.6% of pts would not consider any trade of cure to preserve their larynx
without cancer) 2. Median percentage survival that subjects would trade to preserve their larynx
was 33%
3. 47.9% of pts wanted additional information
Hamilton [27] Newcastle, 2011 114 Healthy subjects (51) XRT vs TL TTO Face-to-face NR 1. CRT: good outcome preferred treatment
UK 2012 COPD pts (63) 2. 32% not willing to change treatment at any cost
3. Among other 68%, median time trade off to change to other treatment is
2.5 years

Abbreviations: COPD, chronic obstructive pulmonary disease; CPS, Chicago Priority Scale; CRT, chemoradiotherapy; DC, direct comparison; HNC, head and neck cancer; Lx, larynx; NR, not reported; RS, rating scale; SG, standard
gamble; TL, total laryngectomy; TTO, Time Trade Off; VAS, visual analog scale; XRT, radiotherapy.
a
Timing for patients only.
b
Date is year of publication, because survey dates were not reported in the article.

49
50 P. Blanchard et al. / Oral Oncology 62 (2016) 4453

Table 5
Health states evaluated and utility values in studies with utility measurement.

Study [ref] Date n Health states Timinga Utility values as measured by TTO (otherwise specified)
b
Jalukar [23] 1998 185 Toxicity >12 mo after trtmt 72 different utility values (6 domains, 4 severity grades for each and 3
participant groups), not reported numerically in the article
Brotherson [29] 20102011 51 Choice of CRT >3 mo after trtmt Not formally reported
over XRT Mean survival percentage difference considered meaningful by patients to
change from XRT alone to CRT: 6% (median: 4%)
De Almeida [24] 2014b 59 Toxicity and type Not relevant Utilities for side effects estimated by healthy subjects (VAS SG)
of treatment 1. Permanent gastrostomy (0.360.81)
2. Esophageal stenosis (0.400.85)
3. Osteoradionecrosis (0.410.85)
4. Permanent tracheostomy (0.440.85)
5. Pharyngocutaneous fistula (0.530.89)
6. Temporary gastrostomy (0.540.89)
Mc Neil [26] 1981b 37 LP vs NR Participants agreed to a mean reduction of life by 14% to maintain their larynx,
laryngectomy corresponding to a 0.86 utility for LP strategy (XRT).
Otto [41] 1997 59 LP vs After trtmt Average utility of laryngectomy compared to LP (XRT):
laryngectomy 1. Among patients: 0.89 (0.44 when restricted to those willing to trade)
2. Among providers: 0.85 (0.67 when restricted to those willing to trade)
Van der Donk 1995 39 LP vs >3 years after Average utilities for XRT/Surgery based strategies compared to normal function
[25] laryngectomy trtmt evaluated by:
1. Lx cancer pts: 0.70/0.65
2. Floor of mouth cancer pts: 0.72/0.64
3. HNC clinicians: 0.90/0.77
4. Healthy subjects: 0.81/0.71
Laccourreye 2010 309 LP vs NR Average utility of laryngectomy compared to laryngeal preservation (CRT): 0.67
[28,42] laryngectomy
Hamilton [27] 20112012 114 LP vs NR Average utility compared to normal function:
laryngectomy 1. LP (CRT) with good outcome: 0.64
2. LP (CRT) with poor outcome: 0.31
3. Laryngectomy with good outcome: 0.57
4. Laryngectomy with poor outcome: 0.33

Abbreviations: CRT, chemoradiotherapy; LP, laryngeal preservation; NR, not reported; SG, standard gamble; TL, total laryngectomy; TTO, Time Trade Off; VAS, visual analog
scale; XRT, radiotherapy.

patients and healthy subjects [17,18,20,2327], major variations
and discordance in terms of priorities were seen. The differences
were the largest when healthy subjects were very different from
cancer patients, such as the medical students in the study by Jalu-
kar et al. [23]. In that study, healthy subjects consistently gave
significantly lower utilities to health states with late toxicity
(i.e., judged them more negatively) compared with patients.
This finding suggests that experiencing a health state may
modify ones judgment about it. Fewer differences were seen
between patients and providers in terms of the quality-of-life
domains of appearance, eating, speech, and breathing. Concor-
dance between healthy subjects and clinical experts was noted
in one study that did not include patients with head and neck
cancer [24]. In that study, the healthy subjects had a mean age
of 35 years and were mostly women, hence very different from
a typical head and neck cancer population. Besides, the presenta-
tion of the clinical cases for the standard gamble strongly favored
surgery, and the experts who had created the cases were also the
ones who scored them.
Variability within patients at different time points
Two studies evaluated patients at different time points [19,20],
but only one study actually studied the same patients at two time
points [19]; the other used different patients for each time point
[20], and a very low sample size precluded any detailed analysis.
Overall these studies showed that the distribution of patient rat-
ings remained broadly similar to those at baseline for most
domains [19], with no indication that patient priorities would
change over time except when considering fear of recurrence,
which decreases with time from initial treatment.
No correlation between priority ranking and quality of life scores
Two studies compared ranking priorities and quality-of-life
scores for patients with head and neck cancer [17,19]. Findings
from one study of 131 patients suggested that patients assign less
importance to items related to areas in which they are functioning
relatively well [17], although the correlations were weak. As an
example, patients who had higher scores, i.e. better function, on
normalcy of diet were less likely to rank swallowing in the top
three priorities compared with those with lower diet-normalcy
scores. In the other study of 48 patients, University of Washington
quality-of-life (UWQOL) scores were compared with symptom
rankings. Apart from pain-related symptoms, none of the quality-
of-life scores showed significant correlation with symptom rating.
In other words there was no statistical correlation between
patients symptoms intensity, as evaluated by the UWQOL scale
and the importance given to that specific symptom, as measured
by the mean ranking [19]. This lack of statistical significance in
the latter study and discordance in these two reports may reflect
the stronger power of the larger study, but correlation coefficients
in both studies were within the same range and showed only weak
correlations, when present, between quality-of-life scores and
ratings.
Studies on laryngeal preservation
This group of four studies [2528] was much more homoge-
neous in terms of the questions asked (utility of laryngectomy
health state or tradeoff between survival and laryngectomy), the
methods used (mostly time trade-off), and the results. Overall
these studies identified a subgroup of patients who would compro-
 P. Blanchard et al. / Oral Oncology 62 (2016) 4453
mise survival for laryngeal preservation, suggesting that contrary
to studies evaluating ranking of priorities, live longer is not nec-
essarily the top priority for every cancer patient. Radiotherapy,
with or without concomitant chemotherapy, was considered the
preferred treatment over surgery in these studies. The utilities esti-
mated for the different health states by one study that included
larynx cancer patients, as well as floor of mouth cancer patients,
head and neck cancer clinicians and healthy subjects were very dif-
ferent between participant groups. Indeed higher utility scores
were given by clinicians and healthy subjects as compared with
the former-cancer patient groups. Besides, although half of the for-
mer laryngeal cancer patients (four of eight) had a preference for
radiotherapy, all except one clinician (seven of eight) preferred this
treatment modality [25]. Although numbers are small, such dis-
crepancies should be taken into consideration. Last, one study
showed that about half of the participants wanted more informa-
tion about the different treatments, cure rates, and risk of late side
effects [28].
Studies of patients with oropharyngeal cancer
In contrast to studies of laryngeal preservation, studies of pref-
erences related to cancer of the oral cavity or oropharynx were
very heterogeneous [19,24,2931]. Participants were mostly
patients, some of whom were selected because they had experi-
enced severe toxicity; some had been treated with either surgical
or non-surgical modalities; many studies used different methods
of assessment; and one study focused on reasons for not enrolling
in a clinical trial [30]. These differences complicate the interpreta-
tion or synthesis of the findings from these studies. Overall, ratings
on the importance of toxicity varied widely, although participants
tended to focus on toxicity related to oropharyngeal disease, such
as issues with speech, chewing, swallowing, or bone necrosis.
One study evaluating preferences with regard to chemotherapy
concomitant with radiation showed that most patients were not
willing to sacrifice more than a 5% chance of cure to avoid
chemotherapy; this statement was influenced by the patients
own experience of toxicity [29]. One study compared TORS with
radiotherapy and concluded, after interviewing healthy subjects
very different from patients with head and neck cancer, that TORS
was the preferred treatment for this disease [24]. In that study, the
presentation of cases favored TORS, especially with regard to lower
rates and duration of potential adverse effects. Evaluation of utili-
ties for health states with side effects showed very low values,
reflecting a poor perceived quality of life, but this might have been
underestimated compared to what patients would have graded.
Indeed, studies that included both patients and healthy subjects
[23] have shown that health utilities are usually underestimated
by healthy subjects.
Discussion
The present systematic review of preferences and priorities rel-
ative to head and neck cancer underscores the work that has
already been accomplished in this field and confirms that patients
and surrogates tended to rank survival over functional endpoints,
at least before treatment and at initial follow-up visits. However,
the studies reviewed also highlight important variability among
participants regarding functional outcomes, as well as substantial
differences between patients and healthy subjects. Priorities, on
the other hand, seemed relatively stable over time after treatment.
Studies of preferences in laryngeal cancer over the years have pro-
vided a consistent message that patients and their surrogates pre-
fer laryngeal preservation via the use of primarily non-surgical
techniques, although the percentage of respondents willing to
51
compromise survival over function varies considerably. Studies
related to oropharyngeal cancer were heterogeneous in both
design and endpoints, complicating the ability to draw meaningful
conclusions from these studies.
The major limitations of the studies reviewed are that most
were cross-sectional and done at a single treatment center, which
limits the generalizability of their findings. Some studies were
also old; although their findings may have been relevant at the
time, improvements in treatments since the publication of those
studies may render those findings less relevant today. The main
example is in laryngeal preservation, in which many improve-
ments have been made in voice rehabilitation after total laryngec-
tomy since the landmark study by McNeil and colleagues [26,32].
Although we acknowledge these limitations, our systematic
review nevertheless provides information on the current gaps in
knowledge and helps to prioritize future studies in this area to fill
those gaps.
Which population should be targeted?
In our opinion, conducting other studies of unselected patients
with head and neck cancer is not likely to contribute much mean-
ingful information, because the needs and survivorship conse-
quences of treatment greatly vary according to the location of
the tumor. Future studies on patient preferences should first tar-
get patients with human papillomavirus positive oropharyngeal
carcinoma, because of both the increasing incidence of the disease
and the high cure rates compared with other head and neck can-
cers [2], although this statement is our opinion and is not based
on published evidence. The risk of severe late side effects and
their substantial effects on the quality of life of survivors [3,33],
especially salivary flow, swallowing function, and dental prob-
lems, have prompted research on the possibility of treatment
de-intensification. And even though the temptation might be to
focus on new treatment modalities (such as TORS or proton ther-
apy), or newer strategies that use less-intensive multimodality
treatments, clinical research should be focused on the endpoints
that matter to patients. Unfortunately the current research as
reviewed here not is not particularly informative as to which end-
points patients prioritize, although the study by Rogers et al. sug-
gested that swallowing, chewing, and speech are three highly
relevant items [19].
Methods for studying patient preferences
A range of methods has been used to investigate stated patient
preferences [16], from easy-to-understand and easy-to-administer
ranking or rating surveys to more sophisticatedbut also more
difficult to administer and interprettime trade-off or standard
gamble methods. In head and neck oncology, different utility mea-
surement instruments have yielded different results; indirect
health utility measures (visual analog scale (VAS) exercises or
multi-attribute utility instruments such as the Euroqol instrument
EQ-5D, for example) may be more valid in this population than
direct measures (standard gamble or time trade-off) [34], possibly
related to cognitive complexity [35,36]. A recent systematic review
of cost-effectiveness in head and neck cancer treatment showed
that studies often yielded conflicting findings [37], even when they
compared treatment modalities within the same clinical approach,
e.g. different modalities of surgery or different modalities of radio-
therapy. Bearing in mind these two important caveats from stated-
preference and cost-effectiveness analyses, we favor the use of a
homogeneous set of standardized endpoints with consensual sta-
tistical analysis, preferably using indirect measures such as VAS
or EQ-5D [38].
52 P. Blanchard et al. / Oral Oncology 62 (2016) 4453
Relevance of patient-preference studies for clinical practice
Development of future studies of patient preferences whose
findings can be translated easily to clinical practice may be
informed from the experience with two distinct sets of previous
studies one for laryngeal preservation and the other for oropha-
ryngeal cancer. The studies of laryngeal preservation all used the
same method, asked similar questions, and provided a consistent
conclusion, that a proportion of participants would be willing to
compromise a certain amount of survival to avoid laryngectomy.
Although the exact proportion may vary from one study to another,
the consistency of this finding supports discussing the various
options for laryngeal preservation with eligible patients. Studies
of preferences in other head and neck cancers suffer, on the other
hand, from significant heterogeneity. Vastly different populations,
different methods, and different underlying hypotheses, make con-
sensus and generalizability of their conclusions very low. We rec-
ommend that future research should focus on the prospective
longitudinal collection of patient centered functional data on
several endpoints and for major treatment strategies. In this
regard, harmonizing the PRO tools used and the frequency of
collection is an essential first step. The findings could then be used
both to inform patients and to develop decision aids and shared
decision-making strategies to encourage patient input in the
choice of initial treatment. The experience and value framework
developed for early prostate cancer, where several different treat-
ments are offered to patients, would be one way to present multi-
dimensional information to patients and let them decide based on
the endpoint that matters the most to each of them [39]. Studies of
patient preference remain important, but their findings ultimately
would be used to define future research strategies and to select the
most appropriate and meaningful quality-of-life endpoints to be
presented to patients during the decision-making process.
In conclusion, although substantial research has been
conducted on patient preferences in the treatment of head and
neck cancer, numerous areas of uncertainty and opportunities for
future research still exist. One example that is currently timely
includes developing a framework of different treatment strategies
with different survivorship consequences for patients with human
papillomavirus-positive oropharyngeal cancer. Currently, evidence
that can be used to inform patients decision as to their own treat-
ment plans is scarce. Gathering standardized patient-centered
data, creating patient-preference studies that include reliable and
generalizable methods, and developing decision aids have emerged
as a top priority for future research.
Grant or financial support
Dr. Blanchard received funding from The Foundation Nuovo Sol-
dati for Medical Research, the Philippe Foundation and the Fonda-
tion pour la Recherche Medicale (FRM) grant SPE20150331822.
Also supported in part by NCI grant CA016672 from the National
Institutes of Health to The University of Texas MD Anderson Cancer
Center, and the Duncan Family Institute.
Conflict of interest
The authors had no conflict of interest with regards to the topic
under consideration in this article.
Acknowledgement
The authors acknowledge the assistance of Greg Pratt, MSIS,
DDS, from MD Andersons Research Medical Library for the refer-
ence search, and of Christine F. Wogan, MS, ELS, from MD Ander-
sons Division of Radiation Oncology, for editorial contributions.
Appendix A. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.oraloncology.
2016.09.008.
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