10.14639/0392-100X-N1099
There is a scarcity of data assessing outcomes of head and neck cancer patients who refuse treatment for potentially curable disease. We report the data of patients who refused curative treatment at a tertiary referral centre and perform a review of the literature. Patients with a potentially curable mucosal head and neck cancers that were discussed at the multidisciplinary tumour board of a referral centre in a two-year period were included. Two cohorts were obtained: patients who accepted the proposed treatment and those who declined it. Statistical analysis was performed using a univariate analysis with parametric and non-parametric tests. Of a total of 803 patients, 14 (1.74%) refused treatment despite being potentially curable. Their median survival was 6.92 months (range 3-12). Patients who refused treatment were older (73.07 years [95% CI, 66.86-79.28] vs 65.56 years [95% CI, 64.70-66.43], p = 0.030) and more likely to have T4 disease (50% vs 26.04%, p = 0.044). Most patients with curable disease accept conventional treatment and those who refuse it experience dismal outcomes. This report provides objective evidence and can be employed to better counsel patients who refuse curative treatment.
application/xml
1827-675X
1099
en
Anthony Nichols
https://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
literature review
Head and neck cancer patients declining curative treatment: a case series and literature review
Text.Serial.Journal
https://www.actaitalica.it/
41
Head and neck
2021-03-19
2020-09-01
2021-03-19
2021-03-24
18-23
1
Anthony Nichols
2021/03/19
10.14639/0392-100X-N1099
18
Otolaryngology-Head and Neck Surgery Department, Western University, London Ontario, Canada
1827-675X
literature review
23
Head and neck cancer patients declining curative treatment: a case series and literature review
https://www.actaitalica.it/article/download/1099/520
41
ACTA OTORHINOLARYNGOLOGICA ITALICA 2021;41:18-23; doi: 10.14639/0392-100X-N1099




Head and neck


Head and neck cancer patients declining curative
treatment: a case series and literature review
Rifiuto di trattamenti curativi nel distretto testa-collo: case series e review
della letteratura
Axel Sahovaler1,2, Tommaso Gualtieri2,3, David Palma4, Kevin Fung1, S. Danielle MacNeil1, John Yoo1, Anthony Nichols1
1
  Otolaryngology-Head and Neck Surgery Department, Western University, London Ontario, Canada; 2 Guided Therapeutics (GTx)
Program, Techna Institute, University Health Network, Toronto, Ontario, Canada; 3 Unit of Otorhinolaryngology - Head and Neck
Surgery, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia,
Italy; 4 Radiation Oncology Department, Western University, London Ontario, Canada


SUMMARY
There is a scarcity of data assessing outcomes of head and neck cancer patients who refuse
treatment for potentially curable disease. We report the data of patients who refused cura-
tive treatment at a tertiary referral centre and perform a review of the literature. Patients
with a potentially curable mucosal head and neck cancers that were discussed at the mul-
tidisciplinary tumour board of a referral centre in a two-year period were included. Two
cohorts were obtained: patients who accepted the proposed treatment and those who de-            Received: September 1, 2020
clined it. Statistical analysis was performed using a univariate analysis with parametric and    Accepted: September 28, 2020
non-parametric tests. Of a total of 803 patients, 14 (1.74%) refused treatment despite being
potentially curable. Their median survival was 6.92 months (range 3-12). Patients who re-        Correspondence
fused treatment were older (73.07 years [95% CI, 66.86-79.28] vs 65.56 years [95% CI,            Anthony C. Nichols
64.70-66.43], p = 0.030) and more likely to have T4 disease (50% vs 26.04%, p = 0.044).          Otolaryngology-Head and Neck Surgery De-
Most patients with curable disease accept conventional treatment and those who refuse it         partment, Western University, Victoria Hospital,
experience dismal outcomes. This report provides objective evidence and can be employed          London Health Science Centre, Department of
to better counsel patients who refuse curative treatment.                                        Otolaryngology - Head and Neck Surgery, Room
                                                                                                 B3-431A, 800 Commissioners Road East
KEY WORDS: head and neck cancer, declining treatment, literature review                          London, ON, Canada N6A 5W9
                                                                                                 Tel. 519-685-8804. Fax 519-685-8567
                                                                                                 E-mail: anthony.nichols@lhsc.on.ca
RIASSUNTO
Obiettivo. I trattamenti per la patologia oncologica del distretto testa-collo possono cau-
sare disfunzioni di parola, di alimentazione e alterazione della percezione, esitando spesso     Funding
                                                                                                 None.
in stati ansioso-depressivi che impattano sulla qualità di vita dei pazienti. Talvolta, questi
pazienti chiedono che cosa succederebbe nel caso in cui scegliessero di non sottoporsi ad
                                                                                                 Conflict of interest
alcun trattamento. Ad oggi c’è una carenza di dati sull’outcome dei pazienti che rifiutano
                                                                                                 The Authors declare no conflict of interest.
trattamenti per malattie potenzialmente curabili.
Metodi. Sono stati inclusi pazienti candidabili a trattamenti curativi con cancro delle vie
aereo-digestive superiori discussi nel periodo 2014-2016 presso un centro di terzo livello,        How to cite this article: Sahovaler A, Gual-
e suddivisi in due gruppi: 1) pazienti che hanno accettato il trattamento e 2) pazienti che        tieri T, Palma D, et al. Head and neck cancer
lo hanno rifiutato.                                                                                patients declining curative treatment: a case
Risultati. Su un totale di 803 pazienti, 14 (1,74%) hanno rifiutato il trattamento. I pazienti     series and literature review. Acta Otorhi-
                                                                                                   nolaryngol Ital 2021;41:18-23. https://doi.
del gruppo 2 erano più anziani (73,07 anni vs 65,56 anni, p = 0,030), più spesso presenta-
                                                                                                   org/10.14639/0392-100X-N1099
vano una malattia locale T4 (50% vs 26.04%, p = 0,044), e la loro mediana di sopravviven-
za è risultata essere 6,92 mesi (range 3-12).
                                                                                                 © Società Italiana di Otorinolaringoiatria
Conclusioni. Questo studio porta alla luce evidenze oggettive sui pazienti che rifiutano il      e Chirurgia Cervico-Facciale
trattamento per malattie potenzialmente curabili del distretto testa-collo e fornisce elemen-
ti utili per dare loro un aiuto efficace ed esaustivo.                                                          OPEN ACCESS
PAROLE CHIAVE: neoplasie della testa e del collo, rifiuto del trattamento, review della          This is an open access article distributed in accordance with
letteratura                                                                                      the CC-BY-NC-ND (Creative Commons Attribution-Non-
                                                                                                 Commercial-NoDerivatives 4.0 International) license. The
                                                                                                 article can be used by giving appropriate credit and mentio-
                                                                                                 ning the license, but only for non-commercial purposes and
                                                                                                 only in the original version. For further information: https://
                                                                                                 creativecommons.org/licenses/by-nc-nd/4.0/deed.en




18
                                                                                           Cancer patients declining curative treatment




Introduction                                                     therapy to corroborate that they were amenable to receive
                                                                 treatment. A value of 0 corresponds to no comorbidity; 1
The morbidity of head and neck cancer treatment can pro-
                                                                 to cardiovascular disease, dementia, chronic pulmonary
foundly affect patients and their families. Patients can ex-
                                                                 disease, rheumatologic disease, peptic ulcer disease, mild
perience lifelong adverse effects including facial disfigure-
                                                                 liver disease, or diabetes; and 2 or greater corresponding to
ment and impairment of speech, swallowing, and breathing.
                                                                 diabetes with chronic complications, hemiplegia or para-
These treatment-related sequelae often result in major psy-
                                                                 plegia, renal disease, moderate or severe liver disease, or
chosocial stress leading to high rates of anxiety and depres-
                                                                 AIDS. Causes of death and management of patients who
sion 1,2. As a result, it is common that patients hesitate and
                                                                 rejected treatment were accounted for.
even initially refuse receiving the proposed therapy after
                                                                 A T-test was employed for continuous data and chi-squared
the treatment and its side effects are explained to them. Pa-
                                                                 test for categorical data. Wilcoxon rank sum test was used
tients tend to ask about the outcomes of not treating the dis-
                                                                 in cases of non-parametric distribution. Statistical signifi-
ease, and what to expect if their cancer remains untreated.
                                                                 cance was determined at the P < 0.05 level. Data analy-
There is a scarcity of data assessing outcomes of head and
                                                                 sis was performed using SPSS 23.0 (IBM Corp., Armonk,
neck cancer patients who refuse treatment for potentially
curable disease.                                                 NY). Institutional research ethics board approval was ob-
The purpose of this study was to assess the outcomes of          tained for this study (REB# 19-5099.3).
head and neck cancer patients who declined conventional
curative treatment, to compare their clinical features with      Results
patients who accepted the proposed curative-intent therapy       Clinical features of patients declining treatment
and to review the literature on this topic. This information
                                                                 A total of 803 patients were available for analysis. Of
may help both patients and clinicians in decision making
                                                                 these, 14 (1.74%) refused treatment despite being poten-
by providing information about the expected outcomes of
                                                                 tially curable. Table I depicts the characteristics of this
not pursuing standard therapy for head and neck cancer.
                                                                 subgroup. Average age at diagnosis was 73 years (range
                                                                 55 to 88 years). Nine patients were male. Six (43%) pa-
Materials and methods                                            tients were married and two (14%) lived with another
The London Regional Cancer Program (LRCP) reviews all            family member, whereas the six (43%) remaining patients
patients who are diagnosed with head and neck cancers in         lived alone with no family support. None had a history of
Southwestern Ontario, encompassing a catchment area of 2         mental illness. The oral cavity was the most common can-
million people. All patients with a suspicion or confirma-       cer site with 7 (50%) cases, followed by the oropharynx
tion of a head and neck cancer are referred to the LRCP          4 (28.5%), larynx 2 (14.2%) and hypopharynx 1 (7.1%).
and evaluated by a head and neck surgeon and a radiation         Most had locally-advanced T-classification, with 7 (50%)
oncologist in a combined clinic. After the consult, the pro-     T4 cancers. Nearly all [13 (92.8%)] had positive cervi-
posed treatment is communicated to the patient with a de-        cal nodes. p16 status was assessed only for oropharyngeal
tailed explanation of the advantages and side effects of the     primaries, and three of the four patients were p16 posi-
treatment.                                                       tive. Eleven patients had a Charlson/Deyo score of 1 (five
We retrospectively analysed all patients with upper aer-         were diabetic and six had cardiovascular disease). The re-
odigestive tract malignancies who were referred to LRCP          maining had a score of 0.
multidisciplinary tumour board from January 2014 till De-
cember 2016. Two cohorts were obtained: patients who ac-         Survival outcomes
cepted the proposed treatment and those who declined it.         The median survival for untreated patients was 6.92 months
Exclusion criteria included locally advanced unresectable        (range 3-12). Comparing cohorts, patients who refused
tumours, patients who had metastatic disease and patients        treatment were older (73.07 years [95% CI, 66.86-79.28]
harbouring comorbidities that precluded any type of cura-        versus 65.56 years [95% CI, 64.70-66.43], p = 0.03) and
tive-intent treatment (surgical or non-surgical).                more likely to have T4 disease (50% vs 26.04%, p = 0.044).
The variables analysed included age, gender, marital status,     There were no significant differences in gender, tumour
presence of psychiatric illnesses, site, tumour and lymph        site, or nodal staging. Table II shows the characteristics of
node staging (according to the American Joint Commit-            both cohorts. Among the untreated cohort, outcomes for the
tee on Cancer [AJCC] 7th edition clinical staging criteria),     p16-positive oropharyngeal cancer patients were compara-
p16 status and overall survival. Comorbidity was measured        ble to p16-negative disease in all sites (7.7 vs 6.7 months,
by the Charlson/Deyo score only in patients who declined         respectively, p = 0.4).



                                                                                                                                   19
A. Sahovaler et al.




Table I. Characteristics of patients declining curative treatment.
 Age       Gender                 Site            T       N        P16       OS        Suggested         Cause of death              Management
                                                                                       treatment
 77              F               Larynx             4   2a                   7           Surgery        Distant metastasis                   -
 71              M              Oral cavity         4   0                    5           Surgery        Distant metastasis              Palliative
                                                                                                                                     chemotherapy
 88              M           Oral cavity            3   2c                   5           Surgery        Local progression            Tracheostomy
 88              F           Oral cavity            2   1                    4           Surgery        Distant metastasis                   -
 67              M           Oropharynx             4   0          +         5          ChemoRT         Local progression            Tracheostomy/
                                                                                                                                         G tube
 64              M              Oral cavity         4   2c                   5           Surgery     Local progression/ distant    Palliative chemoRT
                                                                                                            metastasis
 59              M            Oral Cavity           4   0                    12          Surgery        Distant metastasis              Palliative
                                                                                                                                      chemotherapy
 82              F             Larynx               1   1                    12            RT               Pneumonia                        -
 80              M           Hypopharynx            2   1                     6            RT           Local progression         Tracheostomy/ G tube
 59              F            Oral cavity           4   2c                    3          Surgery        Local progression              Palliative RT
 79              M            Oral cavity           4   2b                    6          Surgery        Local progression              Palliative RT
 55              F           Oropharynx             2   2b         +          8         ChemoRT         Distant metastasis              Palliative
                                                                                                                                      chemotherapy
 76              M           Oropharynx             3   2c         +         7          ChemoRT         Local progression                    -
 78              M           Oropharynx             2   2b         -         8          ChemoRT         Distant metastasis                   -



Table II. Comparison of patients who accepted and patients who declined           Causes of death of patients who declined treatment were
treatment.                                                                        distant metastasis in seven cases, local progression in six
                    Accepted          Declined           p value                  patients and one case of aspiration pneumonia. Manage-
 Age (average)          66.56                 73               0.03               ment of this cohort included palliative treatment for local
 Gender (M/F           589/190                9/5               NS                symptoms and systemic therapy, all in the context of very
 Site                                                           NS                advanced diseases after initial treatment refusals. Sup-
 Oral cavity              267                 7                                   portive and comfort measures such as palliative care, tra-
 Oropharynx               203                 4                                   cheostomy and G-tube placement were also implemented
 Larynx                   163                 2                                   (Tab. I). Fifty percent of the patients were managed at the
 Hypopharynx               30                 1                                   hospital or hospice and the remaining were managed at
 Nasopharynx               23                 -                                   home by palliative care services.
 Other                    103                 -
 T stage                                                (T4 vs T3-1) 0.044        Discussion
 T1                       216                 -
 T2                       239                 4
                                                                                  A unique feature of head and neck malignancies is that
                                                                                  both the disease and treatment carry frequent acute and
 T3                       136                 3
                                                                                  late toxicities that can have profound effects on patients’
 T4                       198                 7
                                                                                  quality of life. Facial disfigurement, impaired oral intake
 N stage                                                        NS
                                                                                  and speech alterations predisposes patients to social isola-
 N0                       354                 1
                                                                                  tion and depression 1. Therefore, after a diagnosis is made
 N1                       69                  4
                                                                                  and the treatment and its side effects are presented to the
 N2a                      75                  3
                                                                                  patients and their families, they face the difficult deci-
 N2b                      137                 2
                                                                                  sion of undergoing curative therapy with the possibility of
 N2c                      101                 4                                   high morbidity, accepting palliative treatment, or declin-
 N3                       53                  -                                   ing treatment altogether in hopes of maintaining quality of




20
                                                                                             Cancer patients declining curative treatment




life 3. In the internet era, patients have access to a myriad of   tions were risk factors associated with patient refusal.
information including the promises offered by alternative          Stage, comorbidities and tumour histology were not ana-
treatments from unreliable sources.                                lysed. Hughley et al. 3 employed the Surveillance, Epide-
Our data has shown that 1.7% of patients presenting to our         miology, and End Results (SEER) cancer registry program
multi-disciplinary clinic elected to decline any convention-       between 1983 and 2011 and identified patients diagnosed
al treatment, including three patients with highly curable         with upper aero-digestive tract cancers, including only pa-
HPV-positive disease. We found that these patients tended          tients aged 70 and older at the time of diagnosis. A total of
to be older and more likely to have T4 disease than patients       35,834 patients was obtained with 3589 (10%) being un-
who accepted the recommended therapy. The use of alter-            treated patients. The median overall survival was 4 months
native medicine treatment was not well documented in the           for the untreated cohort, but risk factors for overall survival
clinical notes; however, the senior investigators note that        were not analysed. Higher stage, primary pharyngeal site
interest in pursuing alternative medicine was a frequently         and black race were all significant predictors of untreated
cited reason for treatment refusal. This paper serves to pro-      status. Finally, Cheraghlou et al. 7 included only patients
vide objective evidence for future patients that while con-        with resectable oral cavity malignancies using the National
ventional treatment has significant toxicity, refusal almost       Cancer Database (NCBD) from 2004 till 2012. Their total
uniformly leads to a rapid demise.                                 cohort was constituted by 36,261 patients, in which 356
There have been few attempts to analyse the subset of pa-          (1%) were untreated. The median overall survival in this
tients who refuse treatment. Kowalski et al. 4 published an        case was 13.7 months, with advanced age, higher T and
experience of 797 patients with a wide range of tumour             N stages, comorbidities, and government insurance being
staging including unresectable and metastatic tumours,             significant risk factors for decreased survival of patients
who refused any sort of treatment in a tertiary referral cen-      declining treatment in a multivariate analysis. Factors as-
tre in Brazil. With a median overall survival of 3.82 months       sociated with treatment refusal in their final model were:
(range 1 day to 4 years), they found that the only predic-         higher T and N stages, age > 75 years, treatment at low/in-
tor for increased overall survival was higher performance          termediate volume facilities and those with no insurance or
status. In their cohort, 19% of patients refused treatment         government insurance. All patients had resectable tumours,
based on their personal choice, whereas the remaining had          but they did not consider comorbidities which might have
advanced untreatable tumours or poor health status that            precluded treatment. Table III summarises the findings of
precluded treatment. Another single institution experience         these studies.
from Great Britain 5 included 44 patients who received no          Our study represents, to our knowledge, the first report to
form of treatment. In that study, median survival was 2.8          include both resectable and operable patients only, all of
months (no range was provided) and they found no signifi-          whom refused treatment despite being potentially curable.
cant differences between overall survival and patient de-          Our overall survival was within the range of prior studies
mographics, AJCC staging, or interventions such as trache-         (2.8 5-13.7 7). Patients declining treatment tended to have
ostomy or gastrostomy tube. In their series, only four (9%)        more advanced local disease 6,7 (present study), which is
patients were amenable to be cured (one of them being 92           understandable as the curative treatment implies more ex-
years old) but refused treatment. The remaining patients           tensive procedures with higher morbidity and disfigurement
harboured metastases or comorbidities that made them               and may have led to treatment refusal. On the other hand,
unsuitable for treatment. There were no “control groups”           treatment refusal with higher stages can be related more
(comparison with patients who accepted the proposed                with the fact that patients already have a negligent and denial
treatment) in these reports.                                       component that results in choosing to not receive treatment.
More recent studies employing large databases have been            Advanced age at diagnosis was also frequently reported as a
published. A multi-institutional analysis by Choi et al. 6 us-     significant factor 6,7 (present study). We had two 88-year-old
ing the Korean Health Insurance Review and Assessment              patients, which were deemed treatable and curable based
Service, identified 605 head and neck cancer patients be-          on their low comorbidity scores and after being assessed
tween 2003 and 2013. Surprisingly, 32.2% were left un-             by the multidisciplinary tumour board. At our centre, age
treated. The median overall survival was 9 months, with            per se does not represent an absolute limitation for offering
advanced age at diagnosis the only significant risk factor         curative treatment, and decisions are made based on patient
for decreased overall survival in a multivariate analysis.         health status, desires and treatment morbidity. The relation
Comparing patients who refused with those who accept-              between advanced age and not receiving treatment has to be
ed treatment, they found that advanced age at diagnosis,           carefully interpreted as advanced age may be confounded
lower socioeconomic status, and lip and oral cavity loca-          by comorbid conditions that impede treatment.



                                                                                                                                     21
A. Sahovaler et al.




Table III. Review of the literature of previous reports.
 Source/Study years            Location             Pt N        Inclusion     Reasons for        Overall     Significant factors    Risk factors for not
                                                (% from the      criteria     no treatment       survival    for overall survival   receiving treatment
                                               total cohort)                                    (months)        (in untreated
                                                                                                                   patients)
 Kowalski et al./1953-         Brazil Tertiary    797 (100%)    UADT SCC,     Unresectable         3.82      Performance status       No control group
 1990                         Referral Centre                  no oncologic        tumours       (1d-54)
                                                                 treatment     (603/74.6%)
                                                                              Clinical status
                                                                                 (52/6.4%)
                                                                              Patient refusal
                                                                                (153/19%)
 Jeannon et al./2006-           Great Britain      44 (9%)      UADT SCC,      Unresectable        2.8              None              No control group
 2007                         Tertiary Referral                no oncologic        tumours
                                   Centre                        treatment        (16/36%)
                                                                              Clinical status
                                                                                  (24/54%)
                                                                              Patient refusal
                                                                                    (4/9%)
 Choi et al./2002-                Korea        195 (32%)    UADT, no           Not provided         9          Advanced age             Advanced age
 2013                            National                   oncologic                                                                  Lower SE status
                                Database                    treatment                                                                Oral cavity locations
 Hughley et al./1983-         United States   3589 (9.7%) UADT, >70 y.o.,     Not provided          4           Not analysed            Higher stages
 2011                       National Database              no oncologic                                                                Lower SE status
                                                            treatment                                                                     Black race
                                                                                                                                       Pharyngeal site
 Cheraghlou et                United States        356 (1%)    Oral Cavity    Patient refusal     13.7         Advanced age             Higher stages
 al./2004-2012              National Database                    SCC, no       (356/100%)                      Higher stages              Age > 75
                                                                oncologic                                        Increased           Low or intermediate
                                                               treatment,                                      comorbidities           volume facilities
                                                               resectable                                       Government             No insurance or
                                                                 tumours                                         insurance          government insurance
 Sahovaler et                Canadian Tertiary    14 (1.7%)     UADT, no      Patient refusal   6.9 (3-12)     Not analysed             Advanced age
 al./2014-2016                Referral Centre                   oncologic      (14/100%)                                               Higher T stages
                                                               treatment,
                                                               resectable
                                                                 tumours
UADT: upper aerodigestive tract.



Although we were unable to do a pair-matched analysis to                        than 50% in a recently published meta-analysis 12. Pa-
compare our cohorts, ours was the only study that included                      tients harbouring laryngeal cancer recurrences treated
only potentially curable and fit patients, and this allowed                     with salvage laryngectomies have a 2 year OS of 71%
us to compare the dismal median overall survival of our                         after organ preservation therapies have failed. All this
series (6.92 months; range 3-12) with the outcomes re-                          surmises that the option of not receiving evidence-based
ported in the literature in similar populations who un-                         curative treatment carries a much worse prognosis, even
derwent a curative treatment. In a recent series of 244                         in the recurrent setting.
patients affected by oral cavity carcinoma (stage I-IV,                         In some jurisdictions, socioeconomic status and its de-
mean age 63.8 years), 5-year OS was 60.5% 8, whereas                            rivatives (e.g. type of insurance) may play an important
none of our patients survived more than a year. An expe-                        role in not treating patients 3,6,7. This is intimately related
rience from our centre showed that even in patients with                        with advanced stages at diagnosis, and even in countries
recurrent oral cavity cancer treated with salvage surgery,                      with universal access to healthcare system 13, individuals
5-year OS was 43% 9, and even higher than in our co-                            with lower socioeconomic status have more limited ac-
hort. Differences with OS of oropharyngeal malignancies                         cess to primary care and periodic health examinations.
are even more notorious, with a reported 3-year OS be-                          Oral cavity 6 and pharyngeal 3 locations were treated in
tween 87%-82% in HPV+ and 57.1%-41% in HPV- pa-                                 smaller proportions in two studies. A potential explana-
tients 10,11. Even in recurrent cases, 5-year OS was higher                     tion with the oral cavity location is that treatment gener-



22
                                                                                                 Cancer patients declining curative treatment




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Acknowledgements                                                     complication rates of different surgical and nonsurgical treatment mo-
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The datasets used and/or analysed during the current study           review and meta-analysis. Head Neck 2016;38:1855-61. https://doi.
are available from the corresponding author on reasonable            org/10.1002/hed.24531
request. This manuscript was presented in the 6th World
                                                                13
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