10.14639/0392-100X-N2762
Objective. The current study systematically reviews the literature about financial toxicity (FT) in head and neck cancer patients. Three databases were reviewed: PubMed, Scopus and Web of Science. Methods. Full text English papers published from 2000 to 2022 reporting on quantitative results about FT in head and neck cancer survivors collected through structured questionnaires or interviews were included.Results. Twenty-seven articles were included. Most of the articles were published after 2015 and from United States. There was a slight prevalence of papers dealing with oropharyngeal cancer, squamous-cell carcinoma and locally advanced head and neck cancer. Measures of FT were obtained through validated questionnaires like COST, FIT and FDQ. Collected data were mostly referrable to financial spending, financial resources, psychosocial aspect, support seeking, coping care and coping lifestyle subdomain. FT scores by COST were found to be worse in the COVID era. Financial counseling and adequate information about the costs of treatment were two effective strategies to mitigate FT. Conclusions. FT is a relatively new challenge in head and neck cancer treatment, whose expenses are higher than therapies for other cancers. A universal method to assess FT and a unified guideline for the administration of questionnaires are needed to mitigate FT and to improve patient outcomes.
text/xml
1827-675X
2762
en
Cesare Piazza
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
financial distress
Measuring financial toxicity in head and neck cancer: a systematic review
Text.Serial.Journal
https://www.actaitalica.it/
44
Reviews
2024-02-27
2023-09-27
2024-02-28
2024-02-28
1-12
1
Cesare Piazza
2024/02/27
10.14639/0392-100X-N2762
1
Unit of Otorhinolaryngology – Head and Neck Surgery, ASST Spedali Civili di Brescia, Brescia, Italy; Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, School of Medicine, Brescia, Italy
1827-675X
financial distress
en
12
Measuring financial toxicity in head and neck cancer: a systematic review
https://www.actaitalica.it/article/download/2762/1068
44
ACTA OTORHINOLARYNGOLOGICA ITALICA 2024;44:1-12; doi: 10.14639/0392-100X-N2762




Review


Measuring financial toxicity in head and neck cancer:
a systematic review
Elisa Raggini1,2, Davide Mattavelli1,2, Gabriele Zigliani1, Paolo Bossi3, Cesare Piazza1,2
1
  Unit of Otorhinolaryngology – Head and Neck Surgery, ASST Spedali Civili di Brescia, Brescia, Italy; 2 Department of Medical and
Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, School of Medicine, Brescia, Italy; 3 Department
of Biomedical Sciences, Humanitas University, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy


SUMMARY
Objective. The current study systematically reviews the literature about financial toxicity
(FT) in head and neck cancer patients. Three databases were reviewed: PubMed, Scopus
and Web of Science.
Methods. Full text English papers published from 2000 to 2022 reporting on quantitative
results about FT in head and neck cancer survivors collected through structured question-
naires or interviews were included.
Results. Twenty-seven articles were included. Most of the articles were published after
2015 and from United States. There was a slight prevalence of papers dealing with oro-
pharyngeal cancer, squamous-cell carcinoma and locally advanced head and neck cancer.
Measures of FT were obtained through validated questionnaires like COST, FIT and FDQ.
Collected data were mostly referrable to financial spending, financial resources, psycho-
social aspect, support seeking, coping care and coping lifestyle subdomain. FT scores by
COST were found to be worse in the COVID era. Financial counseling and adequate infor-
mation about the costs of treatment were two effective strategies to mitigate FT.
Conclusions. FT is a relatively new challenge in head and neck cancer treatment, whose
expenses are higher than therapies for other cancers. A universal method to assess FT and a
unified guideline for the administration of questionnaires are needed to mitigate FT and to
improve patient outcomes.
KEY WORDS: head and neck, cancer, financial toxicity, out-of-pocket cost, financial
distress


Introduction                                                                                  Received: September 27, 2023
                                                                                              Accepted: November 26, 2023
The term financial toxicity (FT), first mentioned in medical literature in 2011 ,        1

encompasses both the objective and subjective financial burden from the per-                  Correspondence
spective of the patient with cancer. Out-of-pocket (OOP) expenses include                     Davide Mattavelli
drugs and medications to cure treatment toxicity, complementary care, home-                   E-mail: davide.mattavelli@unibs.it
care assistance, travel and lodging to follow the treatment regimen, and are
referrable to objective financial burden. These direct costs as well as indirect                How to cite this article: Raggini E, Mattavelli
                                                                                                D, Zigliani G, et al. Measuring financial toxic-
costs such as losing income or work lead to subjective financial distress, which                ity in head and neck cancer: a systematic review.
means worrying for one’s financial situation, looking for economical support                    Acta Otorhinolaryngol Ital 2024;44:1-12. htt-
and using coping strategies to afford all the expenses 2-4.                                     ps://doi.org/10.14639/0392-100X-N2762
Patients with high level of FT at baseline have worse outcomes in term of
                                                                                              © Società Italiana di Otorinolaringoiatria
overall survival and cancer specific survival 5,6. The explanation for this can be            e Chirurgia Cervico-Facciale
multiple. The most obvious is the possibility to decrease the quality of treat-
ments because of limited financial resources; this aspect is highly dependent                                OPEN ACCESS

on the organization of the Health National System (public and universal, or                   This is an open access article distributed in accordance with
                                                                                              the CC-BY-NC-ND (Creative Commons Attribution-Non-
private). Moreover, a selection bias may exist, since patients with higher FT                 Commercial-NoDerivatives 4.0 International) license. The
are likely to have more advanced and heavily treated disease, less qualitative                article can be used by giving appropriate credit and mentio-
                                                                                              ning the license, but only for non-commercial purposes and
health insurance, and lower socio-economic status. Finally, a possible “biolog-               only in the original version. For further information: https://
ic” explanation relies on the stimulation of the sympathetic adrenergic path-                 creativecommons.org/licenses/by-nc-nd/4.0/deed.en




                                                                                                                                                          1
E. Raggini et al.




way by financial hardship, which is a well-known promoter       Materials and methods
of immunosuppression and tumour growth 6.
                                                                Search strategy
The evident negative impact on clinical outcomes under-
                                                                A systematic review of the literature was conducted ac-
lines the importance to quantify, compare and prevent FT
                                                                cording to the Preferred Reporting Items for Systematic re-
with adequate instruments. On one hand, available scales
                                                                view and Meta-Analysis (PRISMA) 2020 statement 12. The
to measure financial toxicity include Financial Index of
                                                                search was conducted on the PubMed, Scopus and Web of
Toxicity (FIT), COmprehensive Score for financial Toxic-
                                                                Science online databases up to September 27, 2022. We re-
ity (COST), Financial Distress Questionnaire (FDQ), Sub-
                                                                stricted the research to English language articles published
jective Financial Distress Questionnaire (SFDQ), Incharge
                                                                from 2000 onward, using appropriate filters.
Financial Distress/Financial Wellbeing Scale, Socioeco-
                                                                The following query (“head” OR “neck” OR “mouth” OR
nomic WellBeing Scale (SWBS) 7-9 and Patient-Reported
                                                                “pharynx” OR “oral cavit*” OR “paranasal sinus*” OR “ac-
Outcome for Fighting FInancial Toxicity (PROFFIT) 10.
                                                                cessory sinus*” OR “nose” OR “nasal cavit*” OR “middle
On the other hand, several questionnaires explore many as-
                                                                ear” OR “larynx” OR “minor salivary gland*” OR “major
pects of patients’ quality of life after cancer diagnosis and
                                                                salivary gland*” OR “thyroid” OR “skin”) AND (“cancer*”
treatment also including the financial situation: European
                                                                OR “tumo#r*” OR “neoplasm*” OR “oncolog*”) AND
Organization for Research and Treatment of Cancer Qual-         (“poverty” OR “financial toxicity” OR “financial distress”
ity of Life Questionnaire (EORTC QLQ-C30), short form           OR “financial stress*” OR “financial burden” OR “financial
Patient Satisfaction Questionnaire (PSQ-18), Cancer Self-       well-being” OR “financial hardship” OR “financial worr*”
Administered Questionnaire (CSAQ) supplement, Cancer            OR “financial difficult*” OR “financial consequence*” OR
Care Outcomes Research and Surveillance (CanCORS)               “material hardship*” OR “economic burden” OR “economic
Consortium Patient Survey and Social Difficulties Inven-        hardship” OR “material hardship” OR “out-of-pocket cost*”
tory (SDI) 9.                                                   OR “out-of-pocket expens*” OR “retirement” OR “bank-
The multidimensional measure of FT in cancer patients           rupt*” OR “debt*” OR “income” OR “work income” OR
has been firstly classified in three broad aspects (material    “earned income” OR “employment income”) was launched.
conditions, psychological response, and coping behaviors).      Two authors (E.R. and G.Z.) together screened the titles and
Then, a recent systematic review, which defined FT as a po-     abstracts and selected articles according to inclusion and ex-
tential consequence of subjective financial distress due to     clusion criteria. Discrepancies were clarified between two au-
cancer-related treatment costs, subdivided the three aspects    thors and consultation with a senior otolaryngologist (D.M.).
in a six subdomains framework (financial spending, finan-
cial resources, psychosocial affect, support seeking, coping    Eligibility criteria
care, coping lifestyle) 3,11.                                   The Participants, Interventions, Comparisons, Outcomes,
Currently, FT has been investigated in several non-head         and Study design (PICOS) model was adopted.
and neck sites, while the evidence in the head and neck is      Inclusion criteria were as follows:
still sparse. However, the impact of FT in the head and neck    1. Full text publications (peer review) with at least 20 pa-
may be particularly severe in view of the relevant treatment       tients;
toxicity and high burden of treatment-related symptoms.         2. FT in adult patients (> 18 years) with malignant head and
Moreover, the heterogeneity of definitions, terms, and             neck tumours of different histology including thyroid, sa-
measures in different healthcare systems make it difficult         livary glands, skin, and unknown primary;
to obtain comparable data; therefore, an overview on the        3. Articles with quantitative results about FT obtained
published evidence on this topic could provide both clini-         through structured questionnaires or interviews;
cians and researchers with precious insights.                   4. Articles with data about objective costs (direct and/or in-
The aim of this systematic review is to depict the overall         direct costs) and patients’ subjective perception of their
burden of FT in head and neck cancer. Due to the lack of a         financial situation.
single method of measuring FT, we referred to the above-        Exclusion criteria were as follows:
mentioned six subdomains framework to subdivide the             1. Abstracts, case reports, clinical conferences, comments,
results and to make the comparison easier. Moreover, we            congress reports, editorial, letters, published erratum;
describe the impact of FT on prognosis, and the factors that    2. Qualitative studies without published or structured ques-
most affect FT and OOP expenses. Finally, we try to high-          tionnaires;
light the existing critical issues in measuring FT in head      3. Articles about FT in paediatric patients or in patients
and neck that should be addressed by future research.              with benign head and neck tumour or lymphoma;



2
                                                                       Measuring financial toxicity in head and neck cancer: a systematic review




4. Series of cancers from multiple sites, where data on head        family member to work more or discussing financial con-
   and neck tumours could not be extrapolated;                      cerns with oncologist/radiotherapist or surgeon were col-
5. FT in patients with HPV-related tumours, where data on           lected in the support seeking subdomain.
   head and neck tumours could not be extrapolated.                 Data on cutting back on medications, skipping follow-up
                                                                    visits, refusing or delaying treatment or tests were collected
Quality assessment                                                  in the coping care subdomain, whereas results on cutting
The quality assessment of each study included was estimat-          back on essentials (food, clothing), moving from home or
ed by two authors (E.R. and G.Z.) independently through             turning off utilities were classified as coping lifestyle.
the Newcastle Ottava Scale (NOS) 13 adapted for cross-sec-          Lastly, absolute values of FT obtained from validated ques-
tional and cohort studies. In case of discrepancies, a defini-      tionnaires were considered as follows: SFDQ percentages
tive evaluation was reached by discussion and consultation          were representative of all the six subdomains, COST and
with the same senior otolaryngologist (D.M.).                       FIT scores were comprehensive of all subdomains exclud-
                                                                    ing behavioral domain (coping care, coping lifestyle and
Data collection                                                     support seeking), whereas FDQ values were referred to fi-
We created a dedicated database collecting most relevant            nancial spending subdomain only.
features of the selected articles on country, study design,
period of observation, healthcare system (according to              Results
Böhm classification, 2013) 14, demographics data, tumour
features with type (surgical vs non-surgical) and intent of         Article collection and quality assessment
treatment (curative or palliative).                                 The bibliographic search returned 5964 titles: 1695 from
In view of the heterogeneity of the articles included, we           PubMed, 2470 from Scopus and 1799 from Web of Science.
grouped them into 4 classes according to their focus: a) im-        A total of 3375 records were screened through title and ab-
pact of different therapies in terms of FT; b) impact of FT         stract evaluation after removal of duplicates (n = 2589).
on patient QoL; c) relation between FT and prognosis; and           Since no article about FT in skin cancers with deducible
d) impact of OOP expenses (drugs and medication, comple-            data on head and neck was found, all skin related articles
mentary care, home care, travel, and accommodation) on FT.          were excluded (n = 176).
In the absence of a standardized taxonomy and a universal           Seventy-eight full-text articles were assessed for eligibility.
method of measuring FT, two authors (E.R. and G.Z.) inde-           Fifty-one were excluded because they were related to FT from
pendently analyzed definitions of financial stress and strain       caregivers’ perspective (n = 3), evaluated QoL after head and
and the questionnaires or interviews used to collect data in        neck cancer treatment with no specific focus on FT (n = 42),
the selected articles.                                              compared FT in benign and malignant head and neck tumours
Percentages from collected articles related to the different as-    (n = 2) or focused on financial barriers to cancer treatment
pects of financial distress were classified according to the six-   (n = 4). Twenty-seven articles were finally included (Fig. 1).
subdomain framework proposed by Witte et al. 3 and questions        According to the NOS 13 the overall quality of the included
from Subjective Financial Distress Questionnaire (SFDQ).            studies was good (median value 7.9; range 7-9).
Data on sufficient financial funds to cover costs related to
cancer treatment, loss of income/employment/work due to             General features
cancer diagnosis and treatment and selling properties or            Most of the studies included (Tab. I) were conducted af-
savings used were referred to financial resources.                  ter 2015 (n = 25/27) 5,7,9,15-36 and mostly in the United
Data on difficulties in paying for cancer-related treatment costs   States (n = 15) 5,15,17,20,21,24-28,31-35. There were 5 studies from
(travel, food, lodging, drugs, tests) or daily household expens-    Asia 9,16,22,23,29, 4 of which were conducted in India 9,16,22,29.
es, financial burden due to OOP expenses, reaching credit card      There were only 5 studies from Europe 18,19,36-38, all from
limit of bankruptcy, making debts after treatment or percent-       Northern Europe: 2 from United Kingdom 37,38, 2 from Ire-
age of health-related spending in relation to household income      land 18,19 and 1 from Norway 36.
were collected in the financial spending subdomain.                 Most of the studies were retrospective (n = 21) 5,9,15-20,23-
In the psychosocial domain, we included concerns about              29,31,33-35,37,38
                                                                                      and unicentric (n = 19) series 5,7,9,15-17,21,22,24,26,29-
current financial situation, financial hardship complained          32,34-38
                                                                             . Prospective or combined retrospective and prospec-
by patients on their families and worsening of financial            tive data collection was conducted in 6 cases 7,21,22,30,32,36.
conditions after cancer treatment.                                  Two retrospective studies were multicentric 18,23, whereas
Data on looking for financial aid (governmental or not, bor-        six articles analysed financial data from national databas-
rowing money or credit, loans, or mortgage), need for a             es 19,20,25,27,28,33.



                                                                                                                                              3
E. Raggini et al.




                                                                             Tumour relevant characteristics
                                                                             Most of the articles (n = 24) specified the head and neck
                                                                             cancer site and/or subsite included in the sample 5,7,9,15-19,23-
                                                                             38
                                                                                . Six articles analysed FT in a single specific site, i.e. thy-
                                                                             roid (n = 4) 24,25,27,31 and oral cavity (n = 2) 23,29. Two articles
                                                                             included all head and neck cancer sites also considering the
                                                                             thyroid and salivary glands 9,16. Three articles considered
                                                                             the oral cavity, pharynx and larynx, clearly excluding skin
                                                                             and salivary gland cancers 7,37,38. Among these three articles,
                                                                             one also excluded thyroid cancers7. One article, comparing
                                                                             FT in head and neck cancer with other cancer survivors,
                                                                             included also skin and thyroid cancers in the latter group 28.
                                                                             Excluding articles focused on one site or subsite, the oro-
                                                                             pharynx was the most frequently represented site (n =
                                                                             8) 5,7,15,17,30,32,34,35, followed by the oral cavity (n = 7) 9,16,18,19,36-
                                                                             38
                                                                                . Excluding articles dealing with FT in thyroid cancers,
                                                                             only six studies described HPV status 5,7,26,32,34,35.
                                                                             Regarding histological type, six articles included only head
                                                                             and neck squamous cell carcinomas (SCC) 15,17,23,35,37,38. The
                                                                             remaining included histological types other than SCC (n =
                                                                             3) 5,7,34 or did not specify the histological types (n = 14) 9,16,18-
Figure 1. Flow-chart for selection of publications.
                                                                             22,26,28-30,32,33,36
                                                                                                  . Two of the four thyroid-related cancer articles
                                                                             specified the most frequent histological type, which was
                                                                             papillary carcinoma 24,31.
Demographics                                                                 For the disease stage, there was a slight prevalence of per-
The sample sizes ranged from 29 to 470,772 participants                      centage of locally advanced (i.e., stage III-IV) head and
whose cancer-related financial burden was collected with                     neck carcinomas (n = 10, > 50%) 7,15,17,22,23,29,30,32,34,35. One
the Medical Expenditure Panel Survey (MEPS).                                 article dealt with only locally advanced SCC 9, whereas
Mean age, reported in 22 5,7,15-18,20,21,24-36,38 of 27 studies, was         seven did not specify the disease stage 9,16,20,25,28,31,33.
58.8 years (SD = 5.7). Five studies did not report the mean                  The treatment modality was heterogeneous: four articles
age of patients but divided the sample into decades 9,19,22,23,37.           considered patients who had surgical (n = 1) or nonsur-
Except for the articles dealing with FT in thyroid cancers                   gical (n = 3) treatment alone 21,31,32,36. Most of the articles
(n = 4) 24,25,27,31, there was a clear predominance of male                  (n = 18) considered surgical, nonsurgical, or combined
                                                                             treatments 5,7,9,15-19,22,24,26,27,29,30,34,35,37,38. Five studies did not
gender (75.9%, SD = 10.4). Of the four thyroid-related ar-
                                                                             specify treatment modality 20,23,25,28,33. The intent of treat-
ticles, one dealt with a sample of Hispanic women with
                                                                             ment was curative (n = 7) 26,27,29,30,36-38, curative or palliative
thyroid cancer 27.
                                                                             (n = 3) 9,16,32 or not specified (n = 17) 5,7,15,17-25,28,31,33-35. These
Eighteen articles reported data on patients’ income 7,9,15,16,20-
                                                                             features are summarized in Table III.
25,27,28,30-32,34,37,38
                        and 16 about employment status (before and
after treatment) 9,15-21,24,25,29,31,32,35,37,38. Eleven articles reported   Measuring financial toxicity
both income and employment status data 9,15,20,21,24,25,31,32,32,37,38,      Structured and validated questionnaires were used to mea-
whereas four studies did not specify either 5,26,33,36.                      sure FT in 12 articles 5,7,9,16,17,25,26,29,32,34-36. The most used was
Thirteen of the 18 studies 5,9,16-22,25-28,31-35 in which insurance          COST (n = 5) 16,29,32,34,35, followed by EORTC QLQ-C30
status was specified were from the United States 5,17,20,21,25-              (n = 3) 5,26,36, FDQ (n = 2) 34,35, SFDQ (n = 1) 9, FIT (n = 1) 7,
28,31-35
         . Due to the private healthcare system, these articles              PSQ-18 (n = 1) 17 and CSAQ supplement (n = 1) 25. Two
also reported the percentage of patients with different types                articles used both COST and FDQ 34,35. The remaining 15
of insurance. The mean percentage of uninsured patients                      articles used self-adapted survey tools to measure FT 15,18-
ranged from 3.1% (SD = 2.8) in United States private                         24,27,28,30,31,33,37,38
                                                                                                     . Most of the studies measured FT after treat-
healthcare system to 60.3% (SD = 30.6) in Ireland and in                     ment (n = 20) 7,9,15,16,18-20,23-25,27-29,31-35,37,38. In other articles, the
the Indian mixed public-private healthcare system. Further                   timing of measurement of FT was heterogeneous: during
information is available in Table II.                                        and after treatment (n = 5) 5,22,26,30,36, after 13 months on



4
                                                                                                Measuring financial toxicity in head and neck cancer: a systematic review




Table I. Most relevant characteristics of studies included in the systematic review.
 Author                           Year          Country          Study design                       Period of observation                        Healthcare system
 Rogers et al. 37                      2012              UK             R           U                  Jan - Dec 2008                                 NHS type
 Rogers et al. 38                                       UK              R           U               Jan 2002 - Dec 2008                               NHS type
 Egestad et al. 36                     2015          Norway             P           U               May 2009 - Nov 2012                               NHS type
 O’ Brien et al. 18                    2016          Ireland            R           M                     Apr 2012                             Mixed public-private HS
 De Souza et al. 21                    2017             USA             P           U               May 2013 - Nov 2014                              Private HS
 Massa et al. 15                       2018             USA             R           U                  May - Oct 2017                                Private HS
 Lu et al. 19                          2019          Ireland            R          NCRI                     2012                               Mixed public-private HS
 Massa et al. 20                                        USA             R          MEPS             Jan 1997 - Dec 2015                              Private HS
 Chauhan et al. 22                                     India           P, R         U                    2015-2016                             Mixed public-private HS
 Amarasinghe et al. 23                              Sri Lanka           R           M                       2016                                Totally free HS to all
 Mady et al. 35                                         USA             R           U                  Jan - Apr 2018                                Private HS
 Mongelli et al. 24                    2020             USA             R           U                  Jan - Jun 2017                                Private HS
 Barrows et al. 25                                      USA             R          MEPS                     2011                                     Private HS
 Hueniken et al. 7                                   Canada             P           U                    2014-2018                                    NHI type
 Beeler et al. 32                                       USA             P           U               May 2016 - Jun 2018                              Private HS
 Dar et al. 16                         2021            India            R           U                        NS                                Mixed public-private HS
 Ma et al. 5                                            USA             R           U               Jan 2013 - Aug 2017                              Private HS
 Farrugia et al. 26                                     USA             R           U               Oct 2013 - Dec 2020                              Private HS
 Chen et al. 27                                         USA             R          SEER             Jan 2014 - Dec 2015                              Private HS
 Khan et al. 30                                      Canada             P           U                    2015-2018                                    NHI type
 Broekhuis et al. 31                                    USA             R           U                       2019                                     Private HS
 Jella et al. 33                                        USA             R          NHIS                  2013-2018                                   Private HS
 Baddour et al. 34                                      USA             R           U                  Jan - Aug 2018                                Private HS
 Lenze et al. 17                       2022             USA             R           U               May 2012 - July 2016                             Private HS
 Dar et al. 9                                          India            R           U                  Jan - Aug 2021                          Mixed public-private HS
 Mott et al. 28                                         USA             R          NHIS                  2013-2018                                   Private HS
 Thaduri et al. 29                                     India            R           U               May 2020 - Oct 2021                        Mixed public-private HS
R: retrospective; P: prospective; U: unicentric; M: multicentric; NCRI: National Cancer Registry of Ireland; MEPS: Medical Expenditure Panel Survey; SEER: Surveillance Epidemiology
End Results; NHIS: National Health Interview Study; NHS: National Health Service, HS: Health Service; NHI: National Health Insurance; NS: not specified.


average from diagnosis (n = 1) 17 and once a month during                                   chosocial aspect (n = 14) 5,15,16,18,19,24-28,31,32,36,38, support seek-
concurrent chemoradiation (n = 1) 21.                                                       ing (n = 10) 9,16,21,22,24,25,31,32,37,38, coping care (n = 3) 15,31,32 and
Five studies reported a mean score of FT using COST:                                        coping lifestyle (n = 3) 27,32,37. Data about both material as-
the lowest and the higher scores were, respectively,                                        pects of subjective financial distress (i.e., financial resources
10.8/44 (Grade 2)16 and 26.5 (Grade 0) 32 (median value                                     and spending) were reported in 11 articles 15,17,21,22,24,25,27,31-
= 21.1 ± 5.9). Four of these five articles reported data on                                 33,37
                                                                                                 , whereas data about all three behavioural subdomains
FT in terms of financial resources (n = 4) 16,29,32,35, financial                           were reported in one article 32. Only a single article reported
spending (n = 2) 32,34, psychosocial effect (n = 2) 16,32 and                               percentages for each subdomain of subjective financial dis-
behavioural aspect (n = 2) 16,32. Two of these five articles re-                            tress 32. For further information see Table IV.
ported that high FT was experienced by 45% and 40.5% of
patients, respectively, by FDQ, whose items are referrable                                  The impact of financial toxicity
to financial spending subdomain 34,35. Only one study used                                  Few articles addressed the factors affecting FT and the im-
the FIT score to assess FT (median value = 11.1/100) and                                    pact of FT on prognosis and QoL (Tab. V).
reported data about financial spending 7.                                                   Three found a correlation between the type of treatment
Considering each subdomain, the most reported data were                                     and FT 15,19,29 and two found a significant impact of OOP
on financial spending (n = 18) 15,17-25,27,28,30-33,37,38, followed                         costs on FT 21,34, while only one demonstrated worse overall
by financial resources (n = 15) 9,15-17,21,22,24,25,27,29,31-33,35,37, psy-                 survival and cancer specific survival in patients with high



                                                                                                                                                                                  5
E. Raggini et al.




Table II. Most relevant patient characteristics of studies included.                    United States, followed by India and Northern European
                          N        Age        M (%)       I     E    U (%)              countries. Financial burden of patients in USA with a mainly
 Dar et al. 16              29         49.5       82.8%       1     1     93.1%         private healthcare system was not comparable to the one of
 Rogers et al. 38           51          61        82.4%       1     1       NS          patients from European countries with national health ser-
 Beeler et al.   32
                            63         64.1        89%        1     1       0%          vices or mixed private-public healthcare systems and from
 Egestad et al. 36          67          60        73.1%       0     0       NS          India, where, despite a mixed private-public healthcare sys-
 Amarasinghe et al. 23      69          NS         87%        1     0       NS          tem, 4.9% of patients on average are below the poverty line
 Baddour et al.     34
                            71          63        67.7%       1     0       0%          for treatment expenses 22. In the articles included, the per-
 Souza et al. 21            73          58        78.1%       1     1       0%          centage of uninsured patients ranged from 3.1% in United
 Thaduri et al. 29          79          49        91.1%       0     1       NS          States private healthcare system to 84.6% in India and 35.9%
 Massa et al.    15
                           100         62.3        74%        1     1       NS          in Ireland mixed public-private healthcare systems.
 Mady et al. 35            104          64        76.9%       0     1      3.4%         Besides these discrepancies, the comparison is even more
 Dar et al. 9              142          NS        85.9%       1     1     96.5%         difficult considering the different level of development of
 Broekhuis et al.     31
                           147          51         27%        1     1       1%          the different countries. European patients benefit from a
 Lenze et al. 17           202         59.6       77.4%       0     1       4%
                                                                                        more uniform healthcare coverage and Americans are cov-
 Chen et al. 27            273          47          0%        1     0       0%
                                                                                        ered through the Affordable Care Act since March 2010,
                                                                                        whereas Indians, who live in a low-middle income country,
 Ma et al. 5               284          61        77.5%       0     0      6.7%
                                                                                        support the healthcare system through OOP payments 3,9.
 Mott et al. 28            311         65.9        69%        1     0      8.8%
                                                                                        In Sri Lanka, where the highest cost portion is borne by
 Farrugia et al. 26        387          62         78%        0     0       5%
                                                                                        the health system and household costs decrease with the
 Hueniken et al. 7         430         61.6       77.2%       1     0       NS
                                                                                        disease stage, the OOP cost for patients with late advanced
 Rogers et al.    37
                           447          NS        71.6%       1     1       NS
                                                                                        oral cancer is 8.7% of the total cost, compared to 28% of
 Chauhan et al. 22         447          NS         90%        1     0     64.2%
                                                                                        those with an earlier stage of disease 23.
 Massa et al. 20           489          65        64.5%       1     1      2.6%
 Lu et al. 19
                           531          NS         68%        0     1      4.9%
                                                                                        Tumour relevant characteristics
 O’Brien et al. 18         583         62.9        67%        0     1     52.5%         Only 4 articles found a relation between site or stage of disease
 Khan et al. 30            657         62.5       77.3%       1     0       NS          and FT. Patients with laryngeal and hypopharyngeal cancer
 Jella et al. 33           710         59.9        42%        0     0      3.8%         and those with advanced disease (stage IV or nodes positive)
 Mongelli et al.    24
                          1743          51         12%        1     1       NS          reported statistically significant 15,26,35 or near significant 34 high-
 Barrows et al. 25       470772        53.8       29.1%       1     1      5.4%         er levels of FT. In addition, patients with oropharyngeal cancer
N: number; M: male; I: income; E: employment status; U: uninsured; NS: not specified.   were found to have higher OOP costs 30. Despite the defini-
Stratification of financial toxicity by income and employment (1, Yes; 0, No).
                                                                                        tion of head and neck malignancies from the American Joint
                                                                                        Committee on Cancer, which comprises tumours between the
level of FT 5 and seven underlined the impact of FT on pa-
                                                                                        thoracic inlet and skull base 40, the 27 articles collected in this
tient QoL 17,19,24,29,35,37,38.
                                                                                        systematic review revealed a clear heterogeneity in considering
                                                                                        thyroid tumours in the group of head and neck cancers.
Discussion                                                                              The psychosocial impact in terms of financial difficulties
Cancer diagnosis and treatment-related FT, along with                                   due to treatment and concern for one’s own financial situ-
physical and psychological burden, is a recent field of re-                             ation reported by thyroid cancer patients ranged from 43%
search associated with poor patient satisfaction and compli-                            to 50% (30.5% in the article dealing with financial hardship
ance, QoL and survival. Khera et al. suggested to consider                              in Hispanic women), resorting to savings from 23.7% to
FT as a traditional side effect of treatment 39. Publications                           38%, reaching one’s credit card limit from 12% to 17.7%,
on this topic are now increasing, but there is still heteroge-                          and bankruptcy from 3% to 9% 24,27,31.
neity in definitions and tools of measurement along with                                The worse psychological (46.1% vs 24%) and material
healthcare systems in different countries. In this context,                             (28.1% vs 19.9%) financial hardship experienced by thy-
this systematic review tried to provide an overview on FT                               roid cancer patients compared to patients with breast, pros-
in patients with head and neck cancer.                                                  tate, colon, and lung cancer may be due to the younger age
                                                                                        of patients with thyroid cancer, less savings, children still
General features and demographics                                                       dependent, and employment linked insurance with higher
Most of the publications included were conducted in the                                 OOP costs and not to Medicare yet 25.



6
                                                                                               Measuring financial toxicity in head and neck cancer: a systematic review




Table III. Tumour characteristics of studies.
                                                                Anatomopathological features                                                       Treatment
                                    Site          HPV+ (%)                      PH (%)                    Stage III-IV (%)              S          NS        S, NS, S + NS
 One included
 Mongelli et al. 24             T                                           Papillary (85%)                     25%                                                 +
 Barrows et al. 25                                                                  -                            NA                                     NA
 Chen et al. 27                                                                     -                          27.3%                                                +
 Broekhuis et al. 31                                                        Papillary (38%)                      NA                     +
 Amarasinghe et al. 23         OC                      -                     SCC (100%)                        91.3%                                    NA
 Thaduri et al.  29
                                                       -                            -                          73.4%                                                +
 Prevalent if more than one specified
 Massa et al. 15               Or                     -                      SCC (100%)                         67%                                                 +
 Lenze et al. 17                                      -                      SCC (100%)                        69.4%                                                +
 Ma et al. 5                                        40.1%                     SCC (93%)                         49%                                                 +
 Hueniken et al. 7                                  42.1%                    SCC (87.2%)                       73.3%                                                +
 Khan et al. 30                                       -                           -                            71.8%                                                +
 Beeler et al. 32                                    33%                          -                             86%                                 +
 Baddour et al. 34                                   31%                     SCC (84.5%)                       73.2%                                                +
 Mady et al. 35                                     43.1%                    SCC (100%)                        79.2%                                                +
 Dar et al. 16                 OC                     -                           -                              NA                                                 +
 O’Brien et al. 18                                    -                           -                             37%                                                 +
 Lu et al. 19                                         -                           -                            37.7%                                                +
 Dar et al. 9                                         -                           -                              NA                                                 +
 Rogers et al. 37                                     -                      SCC (100%)                        26.4%                                                +
 Rogers et al. 38                                     -                      SCC (100%)                         33%                                                 +
 Egestad et al. 36                                    -                           -                            23.8%                                +
 Jella et al. 33               T/P                    -                           -                              NA                                     NA
 Farrugia et al. 26             P                   43.9%                         -                            48.6%                                                +
 Massa et al. 20               NA                     -                           -                              NA                                     NA
 Souza et al. 21                                      -                           -                            100%                                 +
 Chauhan et al. 22                                    -                           -                            62.9%                                                +
 Mott et al. 28                                       -                           -                              NA                                     NA
HPV: human papillomavirus; T: thyroid; OC: oral cavity; Or: oropharynx; P: pharynx; PH: prevalent histology; S: surgical; NS: non-surgical; SCC: squamous cell carcinoma; NA: not
available.


Impact of treatment strategy                                                               scales include Comprehensive Score for financial Toxicity
As expected, multimodality treatment was associated                                        (COST) 16,29,32,34,35, European Organization for Research and
with higher FT 15,19,29. One article, comparing surgical and                               Treatment of Cancer Quality of Life Questionnaire (EO-
nonsurgical treatments in India, showed that patients ex-                                  RTC QLQ-C30) 5,26,36, Financial Distress Questionnaire
perience higher financial distress after surgery along with                                (FDQ) 34,35, Financial Index of Toxicity (FIT) 7, Subjective
chemo-radiotherapy than after radiation alone 22. Likewise,                                Financial Distress Questionnaire (SFDQ) 9, Patient Satis-
multimodality treatments were associated with higher OOP                                   faction Questionnaire (PSQ-18) 17 and Cancer Self-Admin-
expenses. Patients who underwent chemoradiation, surgery                                   istered Questionnaire (CSAQ) supplement from Medical
plus chemoradiation, or radiotherapy alone had to face                                     Expenditure Panel Survey (MEPS) 25. These instruments
higher OOP costs than surgery alone 30.                                                    use different questions to assess and quantify financial bur-
                                                                                           den, as seen in Table VI.
Measuring financial toxicity                                                               While EORTC QLQ-C30, PSQ-18 and CSAQ explore dif-
Instruments used to assess FT were divided into validated                                  ferent aspects of QoL and satisfaction in cancer and non-
or self-adapted questionnaires 15,18-24,27,28,30,31,33,37,38. Validated                    cancer patients, COST, FDQ, FIT and SFDQ have been spe-



                                                                                                                                                                               7
E. Raggini et al.




Table IV. Measuring financial toxicity.
                                                                          Subjective financial distress
                                                   Material                            Psychosocial                                      Behavioural
                              Financial resources         Financial spending               aspect           Support seeking             Coping care             Coping lifestyle
 Massa et al. 15                         +                      +                             +
 Dar et al. 16                                   COST score (mean) = 10.8/44
                                         +                                                    +                       +                        +
 Lenze et al.  17
                                         +                           +
 Ma et al. 5                                                                                  +
 O’Brien et al. 18                                                   +                        +
 Lu et al. 19                                                        +                        +
 Massa et al. 20                                                     +
 Souza et al. 21                         +                           +                                                +
 Dar et al. 9                                                                                     SFDQ = NA
                                         +                                                                            +
 Chauhan et al.      22
                                         +                           +                                                +
 Amarasinghe et al. 23                                               +
 Mongelli et al. 24                      +                           +                        +                       +
 Barrows et al. 25                       +                           +                        +                       +
 Farrugia et al. 26                                                                           +
 Chen et al. 27                          +                      +                             +                                                                         +
 Mott et al. 28                                                 +                             +
 Thaduri et al. 29                               COST score (mean) = 17.9/44
                                         +
 Hueniken et al. 7                               FIT score (median) = 11.1/100
 Khan et al. 30                                                   +
 Broekhuis et al. 31                     +                        +                           +                       +                        +
 Beeler et al. 32                                COST score (mean) = 26.5/44
                                         +                        +                           +                       +                        +                        +
 Rogers et al.  37
                                         +                        +                                                   +                                                 +
 Rogers et al. 38                                                 +                           +                       +
 Jella et al. 33                         +                        +
 Baddour et al. 34                               COST score (mean) = 24.8/44
                                                             FDQ = 45%
 Mady et al. 35                                  COST score (mean) = 25.3/44
                                         +                  FDQ = 40.5%
 Egestad et al. 36                                                                            +
COST: COmprehensive Score for financial Toxicity; SFDQ: Subjective Financial Distress Questionnaire; NA: not available; FIT: Financial Index of Toxicity; FDQ: Financial Distress Ques-
tionnaire.


cifically validated to assess FT. Compared to SFDQ, COST,                                     the six subdomains, also exploring FT from the perspective
FDQ and FIT items do not cover all the six subdomains of                                      of the patients’ family. On the other hand, FDQ, developed
subjective financial distress 9. COST was developed in Unit-                                  at the University of Pittsburgh, is a 2-item questionnaire to
ed States and validated in patients with advanced solid can-                                  assess FT in cancer patients and in those with chronic diseas-
cers. FIT was developed in Canada and validated in head and                                   es 3,7,9,35. Given the heterogenous scales available to quantify
neck cancer patients of any stage. Both FIT and COST were                                     FT that emerged, we followed the subdomains framework
validated in patients after chemotherapy. SFDQ is the most                                    proposed by Witte et al. 3 to ease comparison of the results.
recently developed questionnaire, and has been validated in                                   Twelve articles reported data on material aspects of financial
head and neck radiation oncology patients. Its items cover all                                distress. In addition the direct medical expenditures on treat-



8
                                                                               Measuring financial toxicity in head and neck cancer: a systematic review




Table V. Impact of financial toxicity.                                      ing, taxi fares and paying medical bills) were another relevant
                          Correlation between financial toxicity and:       source of financial distress. In fact, because of these payments
                             Treatment      QoL   Survival   OOP costs      43% of patients were forced to work more 17 and about 50%
 Massa et al.  15
                                  +                                         were not able to make ends meet 18,19. Referring to the United
 Dar et al.16                                                               States, 14.9% reached their credit card limit 24,27, 13% went into
 Lenze et al.17                             +                               debt 31 and 4.4% experienced bankruptcy 24,25,31. Chauhan et al.
 Ma et al.5                                          +
                                                                            reported that 34% of patients suffered from catastrophic health
                                                                            expenditures, while Rogers et al. found that half of patients felt
 O’Brien et al.18
                                                                            that the financial burden was large or unbearable 22,38.
 Lu et al.19                      +         +
                                                                            In comparison with other cancer survivors, those with head and
 Massa et al.20
                                                                            neck cancer must afford higher OOP expenses (3.9% vs 3%) 20.
 Souza et al.21                                                  +
                                                                            Fourteen articles reported data on the psychosocial aspect,
 Dar et al.9
                                                                            which includes concerns about financial situation 15,18,32 and
 Chauhan et al.22                                                           related effect on families 16,19,32 as well as worsening of their
 Amarasinghe et al.23                                                       financial condition after cancer treatment 5,24,26,27,36,38. Two arti-
 Mongelli et al.24                          +                               cles reported comprehensive percentages of psychosocial do-
 Barrows et al.25                                                           main of subjective financial distress. Both are FT comparison
 Farrugia et al.26                                                          articles. In the first one, the psychosocial impact on patients
 Chen et al.27                                                              with thyroid cancer was compared with breast, prostate, lung,
 Mott et al.28                                                              and colon (46.1% vs 24%) 25. In the second, the psychosocial
 Thaduri et al.29                 +         +                               impact in patients with head and neck tumours was compared
 Hueniken et al.7                                                           with skin, thyroid, breast, genitourinary, gynaecological, gas-
 Khan et al.30                                                              trointestinal, melanoma, haematological, lung tumours and pa-
 Broekhuis et al.31                                                         tients with multiple synchronous tumours (73.3% vs 72.3%) 28.
 Beeler et al.32                                                            Data on the behavioural consequences of financial distress
 Rogers et al.37                            +                               were available in 11 articles, but only one reported data on
 Rogers et al.38                            +                               each of the three subdomains 32. To afford medical expenses,
 Jella et al.33                                                             more than 80% of patients asked for government or non-gov-
 Baddour et al.34                                                +
                                                                            ernment aid (India) 9,16, borrowed money (28.2% in United
                                                                            States and India) 16,21,24,25,32, took out a mortgage (4.4% and 7%
 Mady et al.35                              +
                                                                            in United States and India, respectively) 24,37, applied for ben-
 Egestad et al.36
                                                                            efits (63%, United Kingdom) 38, or asked for a family member
QoL: quality of life; OOP: out of pocket.
                                                                            to work more (23%, United States) 21. Nevertheless, 7% of pa-
                                                                            tients skipped follow-up visits 16,32, 9% refused or delayed tests
ment, cancer is associated with indirect costs like loss of income          or treatment 31,32 and 26% did not adhere to medications 32. Pa-
and change in employment status. Several studies analysed                   tients also had to cut spending on food or clothes 27,32,37, move
the relation between employment status and head and neck                    from home or turn off utilities 27. One article reported that
cancer treatment, reporting that 34-52% of working patients                 mean FT scores from COST in cancer survivors (oral, breast
left their job due to the treatment regimen 15,41. Patients com-            and cancer of various sites) slightly worsened between the
plained about changing their employment status 9,15,16,24,25,29,32,37       pre- and post-COVID era (21.1 [SD = 0.7] versus 15.6 [SD =
or income 15,24,31,37, resorting to savings 16,21,24,27,32,33,35, selling   1.2]) 29. Patients reporting high financial distress by FDQ, used
possessions 16,21,22 and not having sufficient financial funds to           in two articles, were 45% and 40.5%, respectively 34,35.
cover the cost of cancer treatment 16,17. The highest percentage
of patients that was forced to stop working after cancer treat-             Financial toxicity, prognosis, quality of life and OOP expenses
ment was around 70% (in India and USA) 9,32 and one article                 Only one article underlined that a high level of financial
reported that almost half of patients who experienced finan-                difficulty at baseline was associated with worse overall sur-
cial burden complained about loss of income 31. Patients were               vival and cancer specific survival in both multivariate and
forced to use coping strategies, such as using savings (62%) or             match paired analysis 5. Interestingly, this finding attributes
selling properties (25%) 21.                                                a prognostic weight to FT just like other major clinical and
OOP expenses (medical tests, travel and transportation, drugs or            pathological factors, which should prompt physicians to
consumables, dental treatment after radiotherapy, petrol, park-             address greater attention to this treatment-related aspect.



                                                                                                                                                      9
E. Raggini et al.




Table VI. Scales to measure FT and their characteristics.
 Questionnaire                                       Items                                                                           Score
 COST                                                        11/11.                                                                 0-4/44
 De Souza 8
 USA                                                8: psychosocial aspect                                               Grade 0 (> 26): no impact
                                                    2: financial resources                                                 Grade 1 (14-25): mild
                                                     1: financial spending                                               Grade 2 (1-13): moderate
                                                                                                                             Grade 3 (0): high
 EORTC QLQ-C30                                                1/30.                                                        1-4/120 (Likert Scale)
 Bjordal et al. 45                                    1: financial difficulty                                             Higher score: better QoL
 Europe
 FDQ                                                          2/2.                                                                Yes/no
 USA                                                 2: financial spending                                                          1-3
                                                                                                                    Grade 1 (mild): Y + no difficulties
                                                                                                                Grade 2 (moderate): Y + some difficulties
                                                                                                             Grade 3 (severe): No + some/extreme difficulties
 FIT                                                          9/9.                                                           Low tox (grade 1)
 Hueniken 7                                            3: financial stress                                                 High tox (grade 2+3)
 Canada                                                4: financial strain                                             0-1 (+ intermediate levels)
                                                     2: loss of productivity                                   Mean of all responses x 100/9 = score/100
                                                                                                                           Lower score: mild FT
 SFDQ                                                        14/14.                                                               0-2/28
 Dar 9                                               2: financial resources                                                 Grade 1 (0-7): low
 India                                               5: financial spending                                                 Grade 2 (8-14): mild
                                                         3: psychosocial                                               Grade 3 (15-21): moderate
                                                      2: coping behaviour                                                 Grade 4 (22-28): high
                                                      2: support seeking
 PSQ-18                                                       2/18.                                                        1-5/90 (Likert Scale)
 Marshall et al. 46                                   2 financial distress                                   Higher score: satisfaction with financial situation
 USA
 CSAQ                                                   6/93 (Section 6)                       MEPS collects data on expenditures related to medical events. The survey
                                                                                                includes 8 sections, and the 6th focuses on the effects of cancer and its
                                                                                                                        treatment on finances.
 ACS, 2011                                            3: support seeking
 USA                                                 2: financial spending
                                                    1: psychosocial aspect
COST: COmprehensive Score for financial Toxicity; EORTC QLQ-C30: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; FDQ: Financial Dis-
tress Questionnaire; FIT: Financial Index of Toxicity; SFDQ: Subjective Financial Distress Questionnaire; PSQ-18: Patient Satisfaction Questionnaire; CSAQ: Cancer Self-Administered
Questionnaire; MEPS: Medical Expenditure Panel Survey; QoL: quality of life; ACS: American Cancer Society.


Further analyses are warranted to confirm the prognostic                                     these seven publications, one dealt with QoL in survivors of
impact of FT in patients with head and neck cancer.                                          thyroid cancer 24. OOP expenses were associated with higher
Health related quality of life, assessed by Functional Assessment                            financial stress 21 and lower COST scores 34.
of Cancer Therapy - General (FACT-G) 17,19, Patient-Reported
Outcomes Measurement Information System (PROMIS) 17,24,                                      Managing financial toxicity
University of Washington Quality Of Life (UW-QOL) question-                                  Along with coping strategies to reduce the impact of FT in terms
naire 35,37,38 and Depression-Anxiety-Stress Scale (DASS-21) 29,                             of QoL and outcomes, mitigation strategies for FT in patients
was negatively correlated with cancer-related FT. Two studies                                with head and neck cancer are needed. In addition to cost-ef-
also found a significant correlation between COST scores and                                 fective strategies within clinical guidelines, financial counseling
QoL: the lower the COST scores, the worse the QoL 29,35. Of                                  can help patients during treatment. Farrugia et al. found a signif-



10
                                                                      Measuring financial toxicity in head and neck cancer: a systematic review




icant increase in financial difficulty score by EORTC QLQ-C30     Patients who did not undergo financial counselling had
at the end of treatment in patients who did not undergo finan-    greater financial difficulty as revealed by questionnaires at
cial counseling (p = 0.002) compared to patients who benefited    the end of treatment.
from a financial counselor and who had no significant different   These findings should prompt clinicians to evaluate and dis-
scores in pre- and post-treatment questionnaires 26,42,43.        cuss this aspect with the patient and his/her family before
Moreover, patients often complain about the lack of treat-        the beginning of treatment to guarantee the best compli-
ment cost-related information received. Broekhuis et al. 31       ance to the treatment plan. Heterogeneity of questionnaires
analysed financial burden in thyroid cancer survivors and         and healthcare systems makes comparisons among stud-
found that 25% of patients were not adequately informed           ies almost impossible, and hinders a clear depiction of FT.
about treatment costs. Giving adequate information about          Improvement of questionnaires and other analytic methods
treatment costs and discussing this with patients would be        (including healthcare system type, socioeconomical patient
another way to mitigate the impact of the expenses of the         status, site, stage of disease and type of treatment intent)
treatment regimen on both patients and family 31,44.              are warranted to better profile the risk of FT for the indi-
                                                                  vidual patient at baseline, during treatment and follow-up,
Limitations                                                       and properly address it. Moreover, a universal guideline for
This is the first systematic review that has attempted to col-    the timing of administration of questionnaires is needed.
lect data about FT in patients with head and neck cancer.
Our review has some limitations. Due to the heterogene-           Conflict of interest statement
ous taxonomy, we could have missed some relevant articles         The authors declare no conflict of interest.
even after the hand-search. A certain degree of subjectiv-
ity in classifying data in each of the six subdomains may         Funding
be present, although we tried to limit this via consensus.        This research did not receive any specific grant from funding
The heterogeneity in healthcare systems and in patient co-        agencies in the public, commercial, or not-for-profit sectors.
horts made comparisons almost impossible. In view of this,
when reporting outcomes, we always specified the country          Author contributions
where the study was conducted, and we advise the reader to        ER, GZ, PB: concept; ER, GZ: data collection; ER, DM: writ-
consider the specific health system for better interpretation     ing – original draft; CP, PB, DM: writing – review and editing.
of data. Due to the heterogeneity among different question-
naires and since only a few studies found significant corre-      Ethical consideration
lations between tumour features, type of treatment, progno-       Not applicable.
sis and FT, a meta-analysis could not be conducted, and the
evidence related to these correlations is still sparse.           References
                                                                  1
                                                                      Zafar SY, Abernethy AP. Financial toxicity, Part I: a new name for a growing
Conclusions                                                           problem. Oncology (Williston Park) 2013;27:80-149.
                                                                  2
                                                                      Zafar SY, Peppercorn JM, Schrag D, et al. The financial toxicity of cancer treat-
FT is a relatively new field of research. Its impact in head          ment: a pilot study assessing out-of-pocket expenses and the insured cancer
and neck cancer is relevant since these patients have to face         patient’s experience. Oncologist 2013;18:381-390. https://doi.org/10.1634/
                                                                      theoncologist.2012-0279
higher OOP expenses than other cancer patients. Among             3
                                                                      Witte J, Mehlis K, Surmann B, et al. Methods for measuring financial toxicity
current questionnaires specifically validated to assess FT            after cancer diagnosis and treatment: a systematic review and its implications.
(COST, FDQ, FIT, SFDQ), only FIT and SFDQ were de-                    Ann Oncol 2019;30:1061-1070. https://doi.org/10.1093/annonc/mdz140
veloped to measure it in patients with head and neck can-         4
                                                                      Carrera PM, Kantarjian HM, Blinder VS. The financial burden and distress
                                                                      of patients with cancer: understanding and stepping-up action on the financial
cer. FT often translates into psychological distress. We sug-         toxicity of cancer treatment. CA Cancer J Clin 2018;68:153-165. https://doi.
gest following the framework proposed by Witte et al. 3 to            org/10.3322/caac.21443
intercept and classify it in terms of material, psychosocial      5
                                                                      Ma SJ, Iovoli AJ, Attwood K, et al. Association of significant financial burden
and behavioural subdomains. The current evidence showed               with survival for head and neck cancer patients treated with radiation therapy. Oral
                                                                      Oncol 2021;115:105196. https://doi.org/10.1016/j.oraloncology.2021.105196
a correlation of FT with the request for financial aid and the    6
                                                                      Qiao G, Chen M, Bucsek MJ, et al. Adrenergic signaling: a targetable check-
consequent psychosocial distress, as well as its detrimen-            point limiting development of the antitumor immune response. Front Immunol
tal effect on QoL and psychological well-being of patients.           2018;9:164. https://doi.org/10.3389/fimmu.2018.00164
Multimodality treatments and advanced disease are asso-           7
                                                                      Hueniken K, Douglas CM, Jethwa AR, et al. Measuring financial toxicity in-
                                                                      curred after treatment of head and neck cancer: development and validation of
ciated with both greater FT and higher OOP expenses. In               the Financial Index of Toxicity questionnaire. Cancer 2020;126:4042-4050.
turn, FT negatively impacts prognosis.                                https://doi.org/10.1002/cncr.33032




                                                                                                                                                      11
E. Raggini et al.




8
     de Souza JA, Yap BJ, Wroblewski K, et al. Measuring financial toxicity as a        27
                                                                                             Chen DW, Reyes-Gastelum D, Veenstra CM, et al. Financial hardship among
     clinically relevant patient-reported outcome: the validation of the COmprehen-          hispanic women with thyroid cancer. Thyroid 2021;31:752-759. https://doi.
     sive Score for financial Toxicity (COST): measuring financial toxicity. Cancer          org/10.1089/thy.2020.0497
     2017;123:476-484. https://doi.org/10.1002/cncr.3036                                28
                                                                                             Mott NM, Mierzwa ML, Casper KA, et al. Financial hardship in patients
9
     Dar MA, Chauhan R, Murti K, et al. Development and validation of Subjective             with head and neck cancer. JCO Oncol Pract 2022;18:E925-E937. https://doi.
     Financial Distress Questionnaire (SFDQ): a patient reported outcome measure             org/10.1200/OP.21.00683
     for assessment of financial toxicity among radiation oncology patients. Front      29
                                                                                             Thaduri A, Garg PK, Malhotra M, et al. Financial toxicity and mental well-
     Oncol 2022;11:819313. https://doi.org/10.3389/fonc.2021.819313                          being of the oral cancer survivors residing in a developing country in the era of
10
     Riva S, Arenare L, Di Maio M, et al. Cross-sectional study to develop and de-           COVID 19 pandemic – a cross-sectional study. Psychooncology 2023;32:58-
     scribe psychometric characteristics of a patient-reported instrument (PROFFIT)          67. https://doi.og/10.1002/pon.6030
     for measuring financial toxicity of cancer within a public healthcare system.      30
                                                                                             Khan MN, Hueniken K, Manojlovic-Kolarski M, et al. Out-of-pocket costs
     BMJ Open 2021;11:E049128. https://doi.org/10.1136/bmjopen-2021-049128                   associated with head and neck cancer treatment. Cancer Rep 2021;5:E1528.
                                                                                             https://doi.org/10.1002/cnr2.1528
11
     Altice CK, Banegas MP, Tucker-Seeley RD, et al. Financial hardships ex-
     perienced by cancer survivors: a systematic review. JNCI J Natl Cancer Inst
                                                                                        31
                                                                                             Broekhuis JM, Li C, Chen HW, et al. Patient-reported financial burden in thyroid
     2016;109:djw205. https://doi.org/10.1093/jnci/djw205                                    cancer. J Surg Res 2021;266:160-167. https://doi.org/10.1016/j.jss.2021.03.051
12
     Page MJ, Moher D, Bossuyt PM, et al. PRISMA 2020 explanation and elabo-
                                                                                        32
                                                                                             Beeler WH, Bellile EL, Casper KA, et al. Patient-reported financial toxic-
     ration: updated guidance and exemplars for reporting systematic reviews. BMJ            ity and adverse medical consequences in head and neck cancer. Oral Oncol
     2021;Mar 29;372:n160. https://doi.org/10.1136/bmj.n160                                  2020;101:104521. https://doi.org/10.1016/j.oraloncology.2019.104521
13
     Ottawa Hospital Research Institute. https://www.ohri.ca/programs/clinical_ep-
                                                                                        33
                                                                                             Jella TK, Cwalina TB, Sachdev R, et al. Prevalence, trends, and demograph-
     idemiology/oxford.asp. Accessed September 20, 2023.                                     ic characteristics associated with self-reported financial stress among head
                                                                                             and neck cancer patients in the United States of America. Am J Otolaryngol
14
     Böhm K, Schmid A, Götze R, et al. Five types of OECD healthcare systems:                2021;42:103154. https://doi.org/10.1016/j.amjoto.2021.103154
     empirical results of a deductive classification. Health Policy. 2013;113:258-      34
                                                                                             Baddour K, Fadel M, Zhao M, et al. The cost of cure: examining objective
     269. https://doi.org/10.1016/j.healthpol.2013.09.003
                                                                                             and subjective financial toxicity in head and neck cancer survivors. Head Neck
15
     Massa ST, Rohde RL, Mckinstry C, et al. An assessment of patient burdens                2021;43:3062-3075. https://doi.org/10.1002/hed.26801
     from head and neck cancer survivorship care. Oral Oncol 2018;82:115-121.           35
                                                                                             Mady LJ, Lyu L, Owoc MS, et al. Understanding financial toxicity in head and
     https://doi.org/10.1016/j.oraloncology.2018.04.024                                      neck cancer survivors. Oral Oncol 2019;95:187-193. https://doi.org/10.1016/j.
16
     Dar MA, Chauhan R, Sharma KK, et al. Assessing the reliability and valid-               oraloncology.2019.06.023
     ity of comprehensive score for financial toxicity (COST) among radiation on-       36
                                                                                             Egestad H, Nieder C. Undesirable financial effects of head and neck cancer
     cology patients in India: a cross-sectional pilot study. Ecancermedicalscience          radiotherapy during the initial treatment period. Int J Circumpolar Health
     2021;15:1219. https://doi.org/10.3332/ecancer.2021.1219                                 2015;74:26686. https://doi.org/10.3402/ijch.v74.26686
17
     Lenze NR, Bensen JT, Farnan L, et al. Association of self-reported financial       37
                                                                                             Rogers SN, Harvey-Woodworth CN, Hare J, et al. Patients’ perception of
     burden with quality of life and oncologic outcomes in head and neck cancer.             the financial impact of head and neck cancer and the relationship to health
     Head Neck 2022;44:412-419. https://doi.org/10.1002/hed.26934                            related quality of life. Br J Oral Maxillofac Surg 2012;50:410-416. https://doi.
18
     O’Brien KM, Timmons A, Butow P, et al. Associations between neighbourhood               org/10.1016/j.bjoms.2011.07.026
     support and financial burden with unmet needs of head and neck cancer survivors.   38
                                                                                             Rogers SN, Harvey-Woodworth CN, Lowe D. Patients’ perspective of financial
     Oral Oncol 2017;65:57-64. https://doi.org/10.1016/j.oraloncology.2016.12.019            benefits following head and neck cancer in Merseyside and Cheshire. Br J Oral
19
     Lu L, O’Sullivan E, Sharp L. Cancer-related financial hardship among head and           Maxillofac Surg 2012;50:404-409. https://doi.org/10.1016/j.bjoms.2011.07.020
     neck cancer survivors: risk factors and associations with health-related quality   39
                                                                                             Khera N, Chang YH, Hashmi S, et al. Financial burden in recipients of al-
     of life. Psychooncology 2019;28:863-871. https://doi.org/10.1002/pon.5034               logeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant
                                                                                             2014;20:1375-1381. https://doi.org/10.1016/j.bbmt.2014.05.011
20
     Massa ST, Osazuwa-Peters N, Adjei Boakye E, et al. Comparison of the fi-
     nancial burden of survivors of head and neck cancer with other cancer sur-
                                                                                        40
                                                                                             Cohen N, Fedewa S, Chen AY. Epidemiology and demographics of the head
     vivors. JAMA Otolaryngol Head Neck Surg 2019;145:239-249. https://doi.                  and neck cancer population. Oral Maxillofac Surg Clin N Am 2018;30:381-
     org/10.1001/jamaoto.2018.3982                                                           395. https://doi.org/10.1016/j.coms.2018.06.001
21
     de Souza JA, Kung S, O’Connor J, et al. Determinants of patient-centered fi-
                                                                                        41
                                                                                             Buckwalter AE. Patient-reported factors associated with discontinuing em-
     nancial stress in patients with locally advanced head and neck cancer. J Oncol          ployment following head and neck cancer treatment. Arch Otolaryngol Head
     Pract 2017;13:E310-E318. https://doi.org/10.1200/JOP.2016.016337                        Neck Surg 2007;133:464. https://doi.org/10.1001/archotol.133.5.464
22
     Chauhan AS, Prinja S, Ghoshal S, et al. Economic burden of head and neck
                                                                                        42
                                                                                             Cherny NI, Sullivan R, Dafni U, et al. A standardised, generic, validated ap-
     cancer treatment in North India. Asian Pac J Cancer Prev APJCP 2019;20:403-             proach to stratify the magnitude of clinical benefit that can be anticipated from
                                                                                             anti-cancer therapies: the European Society for Medical Oncology Magnitude
     409. https://doi.org/10.31557/APJCP.2019.20.2.403
                                                                                             of Clinical Benefit Scale (ESMO-MCBS). Ann Oncol 2015;26:1547-1573.
23
     Amarasinghe H, Jayasinghe RD, Dharmagunawardene D, et al. Economic bur-                 https://doi.org/10.1093/annonc/mdv249
     den of managing oral cancer patients in Sri Lanka: a cross-sectional hospital      43
                                                                                             Schnipper LE, Davidson NE, Wollins DS, et al. American Society of Clinical
     – based costing study. BMJ Open 2019;9:E027661. https://doi.org/10.1136/                Oncology Statement: a conceptual framework to assess the value of cancer
     bmjopen-2018-027661                                                                     treatment options. J Clin Oncol 2015;33:2563-2577. https://doi.org/10.1200/
24
     Mongelli MN, Giri S, Peipert BJ, et al. Financial burden and quality of life            JCO.2015.61.6706
     among thyroid cancer survivors. Surgery 2020;167:631-637. https://doi.             44
                                                                                             Henrikson NB, Tuzzio L, Loggers ET, et al. Patient and oncologist discussions
     org/10.1016/j.surg.2019.11.014                                                          about cancer care costs. Support Care Cancer 2014;22:961-967. https://doi.
25
     Barrows CE, Belle JM, Fleishman A, et al. Financial burden of thyroid can-              org/10.1007/s00520-013-2050-x
     cer in the United States: an estimate of economic and psychological hard-          45
                                                                                             Bjordal K, Ahiner-Elmqvist M, Tolleson E, et al. Development of a European Or-
     ship among thyroid cancer survivors. Surgery 2020;167:378-384. https://doi.             ganization for Research and Treatment of Cancer (EORTC) Questionnaire mod-
     org/10.1016/j.surg.2019.09.010                                                          ule to be used in quality of life assessments in head and neck cancer patients. Ac-
26
     Farrugia M, Yu H, Ma SJ, et al. Financial counseling is associated with reduced         ta Oncologica 1994;33:879-885. https://doi.org/10.3109/02841869409098450
     financial difficulty scores in head and neck cancer patients treated with radia-   46
                                                                                             Marshall GN, Hays RD. The Patient Satisfaction Questionnaire Short-Form
     tion therapy. Cancers 2021;13:2516. https://doi.org/10.3390/cancers13112516             (PSQ-18). Santa Monica CA: RAND, 1994.




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