Keypoint
- Patient’s poor coordination for cancer treatment may cause
unsatisfactory outcomes.
- The primary site, overall stage, patient living distance significantly
affect the compliance of initiating the treatment.
- Patients’ actual residence areas and their transportation methods,
even their caregiver’s transportation methods, should be investigated
initially.
- Any possible aids or subsidies should be considered if a
transportation barrier is noticed during the initial interaction with
the patients.
- A trend of increased initial treatment compliance after the COVID-19
pandemic is observed. The hardware and software resources should be
re-examined and reinforced if the current resources are incapable of
managing the expected increase in the volume of these patients after
the COVID-19 pandemic.
Introduction
Head and neck cancer is globally increasing owing to rising rates of
tobacco use and human papillomavirus infection and is among the most
common cancers worldwide, with high prevalence rates in South Asia,
Brazil, and central Europe.[1, 2] With the development of multimodal
treatments, including immunotherapy, the locoregional control rate and
the overall survival of advanced head and neck cancer patients has
improved significantly in recent decades.[3] However, the outcome
may still be unsatisfactory because of poor coordination with the
patient.[4]
It is already well accepted that interruptions in radiotherapy are
associated with decreased survival in head-and-neck cancer
patients.[5, 6] Additionally, a delayed time of 60 days to the
initiation of treatment is associated with decreased overall survival
and increased recurrence.[7] In general, the treatment outcome is
influenced by the initiation of treatment, postoperative radiotherapy,
and the time from surgery through the completion of postoperative
radiotherapy, also called the treatment package time (TPT).[8-10]
Once the treatment plan has started, countermeasures to factors already
known to result in poor treatment compliance can be adopted more quickly
as the patients in the treatment process are already under specific
surveillance. What might be even more challenging is identifying factors
that result in patient hesitation, even regarding the initiation of
treatment once the diagnosis is made. Unfortunately, few studies have
contributed to understanding these initial non-compliance factors.
The purpose of this study is to retrospectively review and analyze
factors that lead to non-compliance with treatment initiation by
patients with newly diagnosed head and neck cancers.
2. Materials and methods
Data from patients diagnosed with head and neck cancer (oral cavity,
oropharynx, laryngopharynx, and nasopharynx) between January 1, 2018,
and September 30, 2020, at <blinded for review>
Hospital were retrospectively collected and analyzed. Data from a total
of 271 patients were retrieved from our database. After excluding
patients with (1) multiple cancers (2) inconclusive diagnoses, (3) rare
primary cancer sites, such as the nasal cavity, paranasal sinuses, and
salivary glands and (4) primary site unknown, a total of 194 patients
were included in this study. The age distribution ranged from 27 to 93
years, with an average age of 58.0 years, and the male/female ratio was
4.87:1. Patients were divided into two groups, namely, the delayed group
with 76 patients who did not receive standard treatment under medical
advice after cancer diagnosis within a month and the on-time group with
118 cases who received standard treatment under medical advice after
cancer diagnosis within a month.
Patients enrolled in this study were divided into two groups. The
on-time group was defined as patients receiving treatment following
their doctor’s schedule after diagnosis and a cancer staging examination
in <blinded for review> hospital. The delayed
group was defined under the following situations: (1) the patient did
not follow the doctor’s treatment plan after diagnosis and/or cancer
staging in <blinded for review> hospital or (2)
the patient did not follow the doctor’s treatment recommendations after
diagnosis and/or cancer staging in another hospital and came to
<blinded for review> hospital without any
referral for further consultation and management.
The factors which may influence the compliance were categorized by age,
gender, primary cancer site (the oral cavity, nasopharynx, oropharynx,
and hypopharynx-larynx), T stage, N stage, M stage, overall stage
(I-IV), the patient living inside or outside the territorial dominion of
<blinded for review> hospital (Figure 1; the
Wenshan district of Taipei city, and the Shenkeng district, Pinglin
district, and Shiding district of New Taipei city), and before or after
the impact of COVID-19, as defined by the patient visiting our hospital
before or after March 1, 2020, at which time the Taiwanese government
started to raise intensive border and social activity restrictions.
2.3 Multidisciplinary team care
The treatment recommendations and planning of each patient were
conducted by the head and neck tumor board team of specialists including
otolaryngologists, oral and maxillofacial surgeons, medical oncologists,
radio-oncologists, pathologists, radiologists, radiology nuclear
medicine physicians, rehabilitation physicians, nutritionists, social
workers and case managers.
All procedures performed in studies involving human participants
followed the ethical standards approved by the <blinded for
review>-JIRB. (Approval Number: N202101050)
Data were analyzed using SPSS version 16.0 (IBM, Armonk, New York,
USA). Group comparisons of normally distributed quantitative parameters
were analyzed using the t-test and categorical parameters with an χ2
test to examine the difference between patient compliance and the
patient-related factors of age, gender, primary cancer site, T stage, N
stage, M stage, overall stage, residency related to the territorial
dominion of <blinded for review> hospital, and
the impact of COVID-19.
Binary logistic regression analysis was further performed to explore
the association between patient compliance and potential factors.
Independent variables that were included in the binary logistic
regression model were chosen if the p-value was less than 0.3, as
determined by a chi-square test/t-test. Significance was defined as a
p-value of less than 0.05.
3. Results
3.1 Patient Demographics and Descriptive Statistics
Between January 2018 and September 2020, a total of 194 patients
fulfilled the inclusion criteria and were included in the study. Of
these patients, 118 of them were placed in the on-time group, and 76 of
them were placed in the delayed group. The age distribution ranged from
27 to 93 years, with an average age of 58.3±12.1 years, and the
male/female ratio was 4.87:1.
3.2 Factors affecting the Compliance with Curative Intent
Treatment
Table 1 shows the factors that potentially influence the initial
compliance with the standard cancer treatment recommendations. There was
no significant difference in patient compliance by age or gender. The
patients who had oral cavity cancers and nasopharyngeal cancers were
more likely to delay their treatment (50.0% vs. 48.3% and 30.3% vs.
15.3%, respectively, intra-group differences p=0.021). The
non-compliance rate was gradually higher with the increasing stage of
cancer, with 56.9% of patients at stage IV having treatment delays
(intra-group differences p=0.007). Patients living far from the hospital
tended to delay treatment compared to those who lived in the
<blinded for review> territorial dominion (56.9%
vs. 34.7%, respectively, p=0.003). The compliance percentage was higher
after the influence of the COVID pandemic (30.5% vs. 15.8%, p= 0.026).
Table 2 shows a multivariate analysis of factors affecting patient
compliance with treatment. In the binary logistic regression analysis,
the risk of non-compliance was borderline different between the oral
cavity vs. oropharynx (p= 0.092; 95% CI: 0.083-1.207) and significantly
between the nasopharynx vs. oropharynx (p= 0.045; 95% CI: 0.049-0.960).
The patients who had stage IV cancers showed a higher rate of delayed
treatment than the first stage (p= 0.004; 95% CI: 0.793-0.585).
Patients living far from the hospital were more likely to delay
treatment than those living in the <blinded for
review> territorial dominion (p= 0.013; 95% CI:
0.191-0.820). A trend of increased initial treatment compliance after
the COVID-19 pandemic can still be observed with a p-value of 0.137
(95% CI: 0.803-4.942).
Discussion
In this study, we found that factors including primary site, stage,
distance to the hospital, and even the influence of the COVID-19
pandemic might affect the compliance of curative-intent treatment in
patients with newly diagnosed head and neck cancers. The findings in
this study provide important information about the factors influencing
the intention and initiation of the recommended treatments, which is
also very important but seldom addressed in the existing literature
compared to issues regarding treatment compliance during head and neck
cancer therapy.
The importance of treatment compliance
has been broadly addressed in almost every human disease; the ideal
outcome is never to be expected for a particular treatment if the
treatment compliance is compromised.[11] Many studies have already
addressed the importance of compliance during treatment in the field of
head and neck cancers. Patel et al. conducted a study to determine if
poor compliance with chemoradiation results in an increased rate of
persistent neck disease. Their study included 40 patients with N+ stages
III/IV squamous cell carcinoma of the upper aerodigestive tract treated
with curative-intent chemoradiation who underwent subsequently planned
neck dissection. The authors demonstrated that noncompliance was the
only variable that had a significant correlation with positive pathology
results.[12]
Nevertheless, what if the patient has no intention to engage in
treatment or is unwilling to accept the standard treatment
recommendations? While it is generally agreed that timely care regarding
the initiation of treatment, postoperative radiotherapy, and treatment
package time is associated with survival for patients with head and neck
cancer, there are still many issues left unanswered, including
identifying barriers to timely care, which we would like to investigate
in this study to hopefully help generate strategies to overcome these
problems.[9] Liao et al. reported that patients with a delay in time
to treatment initiation exceeding 60 days had poorer survival and a
greater risk of recurrence.[7] More recently, Chang, Y. L., et al.
examined 1095 HNC patients to identify the factors and reasons impacting
the discordance with the treatment plan in head and neck cancer patients
and to compare the differences between the concordant group and the
discordant group. The authors found that patients with advanced cancer
stages, advanced age, and treatment plans of best supportive care (BSC)
or surgery combined with radiation (RT), chemotherapy (CT), or
chemoradiation (CCRT) were more likely to have discordance with their
treatment plan. [13]
In 2006, under the United Kingdom NHS system, Duvvi et al. proposed a
two-week rule for suspected head and neck cancer and reported that
compliance with the two-week referral guidelines was associated with a
higher cancer detection rate and hopefully demonstrated an improvement
in outcome.[14] In India, it has been demonstrated that early
treatment decisions and referral could significantly improve patient
dropout rates and possibly compliance with treatment.[15] The
authors proposed that the decentralization of cancer care is urgently
needed to manage the high numbers of patients presenting to tertiary
care centers. Many of the problems revealed by these studies seem to be
highly related to healthcare availability issues. This finding makes our
study result even more interesting, as in Taiwan, over 98% of the
population is covered by the national health insurance [16, 17];
with such a high level of healthcare availability, affordability, and
accessibility, what is left to substantively influence patients’ initial
treatment intentions might be especially noteworthy. We believe that the
factors revealed in our study are less likely to be resolved along with
socio-economic growth, which often leads to an increase in health
investments.[18, 19]
In our study, patients with stage IV diseases tend to have a high chance
of not being compliant with our treatment recommendations. While a
patient with higher severity is usually more likely to seek more
treatment options in dealing with higher threats to their health, it is
interesting that the primary site also influences the initial treatment
intentions. The result might be associated with the impact of oral
cavity cancer treatment, which remains a major problem as treatments in
the oral cavity very often lead to a significant alteration in
appearance, speech, smell, and swallowing functions.[20, 21]
Interestingly, our study also demonstrated that patients with
nasopharyngeal cancer tend to be non-compliant. Compared to oral cavity
cancer patients, these patients belong to a completely different entity,
as patients with nasopharyngeal cancer tend to have indolent symptoms
and signs; they might subjectively feel they are not critically ill,
which is a factor that encourages them to spend more time searching for
second opinions.[22]
The finding that distance significantly influenced the initial treatment
intentions is particularly important in this study, especially as
demonstrated in Taiwan. With a crowded population under a very high
density of available healthcare providers, it is noteworthy that a
district classified as being outside the <blinded for
review> Hospital territorial dominion is actually very
often still within a one-hour driving distance to the hospital. It has
already been demonstrated in patients with colorectal cancer that
patients with uncontrolled pain or less social support have greater odds
of transportation barriers and the authors concluded that inquiring
about accessible transportation should become a routine part of cancer
care.[23] More recently, a study investigating the role of
transportation barriers in cancer patients’ decision-making regarding
the treatment process demonstrated that lack of access to transportation
has a significant impact on cancer patients’ decisions concerning
stopping or continuing treatments.[24] This study also showed that
limited access to private vehicles will likely lead to the stopping of
radiotherapy. Based on these findings, we recommend that patients’
actual residence areas and their transportation methods, even their
caregiver’s transportation methods, should be investigated initially.
Furthermore, any possible aids or subsidies should be considered if a
transportation barrier is noticed during the initial interaction with
the patients.
Although it did not reach significance, probably due to insufficient
case numbers, a trend of increased initial treatment compliance after
the COVID-19 pandemic could be clearly observed. Little has been
addressed on this issue regarding the changes in patient behavior
compared to the impact on the healthcare system. As treatment in head
and neck cancer is likely to take place in a virtual instead of
telemedicine settings, doctors and other healthcare providers should be
aware that these patients tend to stay at the nearest accessible
facility to start their treatments once the diagnosis of head and neck
cancer has been made. Thus, the hardware and software resource quantity,
quality, and availability for the multidisciplinary team, including
surgeons, medical and radio-oncologists, psychiatrist, nutritionists,
and social workers, should be re-examined and reinforced if the current
resources are incapable of managing the expected increase in the volume
of these patients after the COVID-19 pandemic.
There are several limitations to our study. First, the selection bias
issue, as seen in the retrospective study design, means that the
proportion of patients visiting our hospital might not be evenly
distributed, which could affect the actual disease incidence rate.
Second, the address information documented might be different from the
patient’s actual residence, and the address of the caregiver was not
investigated in this study. Thus, the transportation barrier
demonstrated in this study should only be regarded as a rough
estimation.
Conclusion
The primary site, overall stage, patient living distance to the
<blinded for review> territorial dominion, and
the impact of COVID-19 might affect the compliance of curative-intent
treatment in patients with newly diagnosed head and neck cancers. While
the impact on outcome remains to be determined, physicians and
healthcare providers might consider adding more resources and strategies
to enhance patient information and early patient participation with
regard to shared decision making and to further lower barriers to
patient transportation in order to increase the compliance of initiating
the treatment in patients with head and neck cancers.
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