High End-of-Life Health Care Utilization in a Contemporary Cohort of Head and Neck Cancer Patients Treated with Immune Checkpoint Inhibitors

Abstract

Background/Objective:

End-of-life health care utilization (EOLHCU) is largely uncharacterized among patients with recurrent/metastatic head and neck squamous cell carcinomas (RMHNSCC), particularly now that immune checkpoint inhibitors (ICI) have been introduced to the treatment landscape. We examined this in a single-institution, retrospective study.

Design/Settings:

We utilized a database of deceased, ICI-treated RMHNSCC patients to obtain demographic and EOLHCU data, the latter of which included advanced care plan documentation (ACPD) and systemic therapy or emergency room (ER)/hospital/intensive care unit (ICU) admission within 30 days of death (DOD). This was compared with a cohort of deceased thoracic malignancy (TM) patients in an exploratory analysis. Multivariate analysis was performed to examine for association between patient factors (such as age, Eastern Cooperative Oncology Group (ECOG) performance status, or smoking status) and overall survival (OS); associations between the said patient factors and EOLHCU were also evaluated. This study was conducted at an academic, tertiary center in the United States.

Results:

The RMHNSCC patients (n = 74) were more likely to have ACPD (p < 0.01), an emergency department visit (p < 0.01), and/or hospital admission (p < 0.01) within 30 DOD relative to the TM group. There was no difference in ICU admissions, ICU deaths, or systemic therapy at end of life (EOL). The OS declined in association with ECOG performance status (PS) and smoking. No association was observed between patient factors and any EOLHCU metric.

Conclusions:

At our center, patients with ICI-treated RMHNSCC have higher rates of both ACPD and EOLHCU, suggesting high symptom burden and representing opportunities for further study into supportive care augmentation.

Introduction

End-of-life care is an integral component of comprehensive oncologic care and an emerging metric for value-based health care delivery. A growing body of research is examining the efficacy and value of interventions at end of life, particularly in patients with advanced, incurable malignancies, where life-sustaining interventions are associated with high morbidity and cost.¹

End-of-life health care utilization (EOLHCU), which encompasses emergency department (ED) inpatient and intensive care unit (ICU) admission within one month of death, chemotherapy within two to four weeks of death and the absence of a hospice referral,² are costly interventions^3,4 that are also associated with decreased patient/family quality of life⁵ and increased decisional regret.⁶ Such care is no longer considered appropriate in the majority of patients with cancer per the American Society of Clinical Oncology (ASCO)'s Quality Oncology Practice Initiative (QOPI),⁷ although published observational studies describe high rates of aggressive end-of-life care, particularly in younger patients.⁸

There is a paucity of literature comprehensively examining the earlier described end-of-life utilization metrics among patients with incurable, recurrent/metastatic squamous cell carcinomas of the head and neck (RMHNSCC). Survival in this population is influenced by p16 status⁹ and is generally estimated at median of 12–24 months.¹⁰ Due to the anatomic location of these cancers, symptom burden can be profound and may occur as a direct result of the disease itself (especially in patients with locoregional recurrence)¹¹ or as a sequela of surgery, chemotherapy, or radiotherapy.¹²

Treatment remains palliative in intent, but it has evolved with the approval of immune checkpoint inhibitors (ICI), monoclonal antibodies that target programmed cell death protein 1 (PD-1). These agents can be efficacious in a subset of patients and are associated with a favorable adverse event profiles compared with cytotoxic chemotherapy.¹³ As a result, ICIs are now established as standard-of-care for RMHNSCC patients, either in the first line (alone or in combination with chemotherapy) or after prior platinum exposure. ICI-treated RMHNSCC patients, therefore, represent an expanding contemporary population.

We examined the patterns of end-of-life care and resource utilization in a modern cohort of ICI-treated RMHNSCC patients at our institution by using available EOLHCU metrics. These metrics have been collected for our upper aerodigestive disease group (thoracic and head and neck malignancies) as a QOPI since 2013. We also sought to explore potential variations in EOLHCU in this group by comparing these with an available EOLHCU dataset of thoracic malignancy (TM) patients. We additionally evaluated for potential associations between individual patient characteristics and both EOLHCU and survival. We collected this data with the aim of guiding institutional efforts at improving end-of-life planning and reducing low value interventions in this growing population.

Methods

Study population

We identified patients with RMHNSCC recorded in an institutional, IRB-approved database who were both deceased and had accessible end-of-life data, the latter of which was collected as a quality improvement initiative. All of these patients received care at our institution and at least one dose of an ICI.

Demographic, disease, and treatment data were obtained from the patients' electronic medical record. The EOLHCU data were collected, with “end-of-life” defined as “within 30 days of death.” EOLHCU was obtained from a separate, above-described institutional database for patients with cancer maintained for quality initiatives. Health care utilization included any intravenous systemic therapy administration given within our network of institutions, as well as visits to in-network EDs, and inpatient or ICU admissions. The presence/absence of advanced care planning documented within the patients' electronic medical record was recorded; specifically if the patient had a “Physician Orders for Life-Sustaining Treatment” (POLST) form, designated power of attorney (DPOA), or any advanced health care directive on file.

Our TM cohort included patients who received care at our institution for a TM and subsequently died. The ICI use was not recorded and was, therefore, unknown.

This project was reviewed and approved by the Fred Hutchinson Cancer Research Center institutional review board.

Statistical analysis

In an exploratory analysis, EOLHCU was compared with a cohort of 379 deceased TM patients using a chi-square test to examine potential differences in EOLHCU in the head and neck patient cohort. The OS was also evaluated; this was defined as time from initiation of ICI to death from any cause and was estimated by using the Kaplan Meier method. Multivariate analysis for factors associated with survival was performed by using a Cox proportional hazards model.

Results

We identified 228 patients with RMHNSCC treated with ICI between the years 2013 and 2019. One hundred and nine patients had died, and 74 (68% of the total) had EOLHCU data; the remaining 34 died outside of our health care system with no available EOLCHU data. The median survival of this patient population was 173 days (range: 10–1918). The demographic distribution of the 74 deceased patients' data is detailed in Table 1.

Table 1.

Patient and Tumor Characteristics

	N = 74 (%)
Age
<40	6 (8)
40–59	27 (37)
60–79	38 (51)
>80	3 (4)
Race
White (Hispanic)	2 (3)
White (Non-Hispanic)	58 (78)
Black	2 (3)
Asian/Native American/Pacific Islander	8 (11)
Unknown	4 (4)
Sex
Male	55 (75)
Female	18 (24)
Unknown/Other	1 (1)
Smoking status
Current	5 (7)
Former	41 (55)
Never	28 (38)
>10 PYH	60 (81)
Site
Oral cavity	28 (38)
Oropharynx	24 (32)
Larynx	8 (11)
Nasopharynx	5 (7)
Cutaneous SCC	4 (5.5)
Hypopharynx	1 (1)
Primary site unknown or not documented	4 (5.5)
Virally mediated
Yes	48 (65)
No	24 (32)
Unknown	2 (3)
Prior curative therapy
Yes	71 (96)
No	3 (4)
Distant metastases
Yes	42 (57)
No	32 (43)
ECOG
0	15 (20)
1	37 (50)
2	20 (27)
3	1 (1)

ECOG, Eastern Cooperative Oncology Group; SCC, squamous cell carcinoma.

The median age was 62 (range = 25–90), with most patients being white (N = 60, 81%) males (n = 55, 74%) with a >10 pack year tobacco history (n = 60, 81%). The most common primary sites were the oral cavity (n = 28, 38%) and oropharynx (n = 24, 32%). Seventy one people (95%) were previously treated with curative intent therapy. Forty two (57%) had distant metastases at the time of ICI administration; the remaining represented locoregional recurrence. Virally mediated cancers (HPV related oropharynx cancer or endemic nasopharyngeal cancer) comprised 65% (n = 48) of the cohort.

At the time of initiation of ICI, ECOG performance status was 0 in 15 (20%) patients, 1 in 37 (50%) patients, 2 in 20 (27%) patients, and 3 in 1 (1%) patient. Forty two (57%) patients received ICI off-trial; 18 (42%) of these off-trial patients had an ECOG ≥2.

Table 2 details EOLHCU in the 74 RMHNSCC patients, as well as a non-head and neck TM cohort, which were compared in an exploratory analysis. Systemic therapy was administered to 4% of RMHNSCC patients within seven days of death (DOD); 8% received therapy within 14 DOD and 24% within 30 DOD. Among the patients who received systemic therapy within 30 DOD, 12 received ICI, whereas 6 received cytotoxic therapies that included cetuximab, paclitaxel, and/or capecitabine. When compared with the TM group, rates of systemic therapy administration within 7, 14, and 30 DOD were similar.

Table 2.

End-of Life Metrics and Advanced Care Planning Documentation in Recurrent/Metastatic Head and Neck Squamous Cell Carcinomas and Thoracic Malignancy Patients

	RMHNSCC (N = 74) (%)	TM (N = 379) (%)	p
Systemic therapy within 7 DOD			0.63
Yes	3 (4)	9 (2)
No	68 (92)	370 (98)
Data not available	3 (4)	0
Systemic therapy within 14 DOD			0.76
Yes	6 (8)	25 (7)
No	65 (88)	354 (93)
Data not available	3 (4)	0
Systemic therapy within 30 DOD			0.31
Yes	18 (24)	72 (19)
No	54 (73)	307 (81)
Data not available	2 (3)	0
ACP—POLST on file			0.03
Yes	31 (42)	108 (29)
No	43 (58)	271 (71)
ACP—DPOA on file			0.06
Yes	26 (35)	91 (24)
No	48 (65)	288 (76)
ACP—HCD on file			0.04
Yes	20 (27)	61 (16)
No	54 (73)	318 (84)
ACP—Any ACP on file			<0.01
Yes	49 (66)	173 (46)
No	25 (34)	206 (54)
ED visit within 30 days			<0.01
Yes	30 (41)	74 (19)
No	41 (55)	305 (81)
Data not available	3 (4)	0
Inpatient admission within 30 days			<0.01
Yes	30 (41)	66 (17)
No	41 (55)	313 (83)
Data not available	3 (4)	0
ICU admission within 30 DOD			0.81
Yes	7 (10)	31 (8)
No	64 (86)	348 (92)
Data not available	3 (4)	0
Death in the ICU			0.40
Yes	5 (7)	15 (4)
No	66 (89)	364 (96)
Data not available	3 (4)	0

Bold highlights statistically significant results.

ACP, advance care planning; DOD, days of death; DPOA, designated power of attorney; ED, emergency department; HCD, health care directive; ICU, intensive care unit; POLST, Physician Orders for Life-Sustaining Treatment; RMHNSCC, recurrent/metastatic head and neck squamous cell carcinomas; TM, thoracic malignancy.

However, RMHNSCC patients were more likely to have some form of advance care planning (ACP) documentation (66% vs. 45%, p < 0.01)—specifically, a completed POLST form (42% vs. 29%, p = 0.03) or health care directive (27% vs. 16%, p = 0.04). In addition, RMHNSCC patients were more likely to have an ED visit (42.3% vs. 19.5%, p < 0.01) and/or a hospital admission (42.3% vs. 17%, p < 0.01) within 30 DOD.

On univariate and multivariate analysis (Table 3), an association was seen between OS and ECOG PS (ECOG 2–3 vs. 0: hazard ratio [HR] = 7.76, p = 0.00002, 95% confidence interval [CI] = 3.07–19.64; ECOG 1 vs. 0: HR = 2.97, p = 0.008, CI 1.33–6.62), as well as between OS and smoking (current/former smokers vs. never HR = 2.18, p = 0.007, CI = 1.24–3.84).

Table 3.

Multivariate Model

	HR	CI (low)	CI (high)	p
ECOG 1 vs. 0	2.97	1.33	6.62	0.008
ECOG 2-3 vs. 0	7.76	3.07	19.64	0.00002
Smoking: Former/Current vs. Never	2.18	1.24	3.84	0.007
Viral mediation: Yes vs. No	0.63	0.34	1.15	0.13

CI, confidence interval; HR, hazard ratio.

We found no association between patient factors such as age, ECOG PS, or smoking status and any EOLHCU metric on univariate analysis of the RMHNSCC cohort.

Discussion

In spite of progress in the treatment of RMHNSCC brought about by the approval of ICI, this patient population continues to have both a poor prognosis and a heavy symptom burden that adversely impacts quality of life.¹¹ Our data shed light on comprehensive EOLHCU patterns in a contemporary cohort of ICI-treated RMHNSCC patients, now representative of the overwhelming majority of RMHNSCC patients. Although most patients in our population had ACP documentation, exploratory analysis demonstrated higher rates of EOLHCU when compared with a similar TM cohort.

Published reports of EOLHCU metrics in RMHNSCC are disparate, noncomprehensive and were observed before the approval of ICI in RMHNSCC. In a population-based cohort of 25,816 Taiwanese patients with head and neck cancer who died between 2009 and 2011, 96.1% had at least 1 indicator of “aggressive care” at the end of life, 35% died in the inpatient setting, and 23% died in the ICU.¹⁴

Shuman et al., in a report of 371 deceased patients with head and neck cancer treated at the University of Michigan in 2011, found that 90% had an advanced directive and 31% died in the hospital.¹⁵ A multicenter, retrospective study of patients with head and neck cancer treated in the United Kingdom found that 31% of 109 deceased patients died in the hospital setting.¹⁶ These high rates of hospital admission/death appear to occur in spite of palliative care team involvement.^17,18 For example, among a cohort of 59 deceased, Finnish RMHNSCC patients who were managed at a specialized palliative center, 66% had an emergency visit and 35% were hospitalized.¹⁹

The relative EOLHCU burden of RMHNSCC compared with non-head and neck malignancies is similarly poorly described in literature. Our exploratory analysis reveals statistically higher rates of ED visits and hospital admissions with 30 DOD among RMHNCC compared with a thoracic malignancy cohort. This observation is likely a result of a complex interaction of factors and may reflect the high symptom burden associated with RMHNSCC.

End-of-life issues relating to airway patency, dysphagia, pain, bleeding, or wound care are challenging to manage in a home environment.^14,16,19,20 Frequent presentations to hospital may, therefore, represent a “symptom crisis” subclass of aggressive EOL care,²¹ rather than an intent to prolong life. This observation suggests an opportunity for supportive care augmentation, as well as patient and care team education in end-of-life planning with these symptoms in mind.

There is a similar paucity of studies regarding the use of systemic therapy for RMHNSCC at end of life. Chang et al., in the aforementioned Taiwanese study, reported that nearly 70% of patients received chemotherapy in the last month of life.¹⁴ In our patient cohort, 24% received systemic therapy within 30 DOD; this is similar to large, European/North American single institution reports of systemic therapy administration among patients with various malignancies.^18,21,22

Our observed rates of systemic therapy administration within 7, 14, and 30 DOD may demonstrate insight by both the patient and treating physician as to the futility of further systemic therapy. It may also reflect reimbursement policy changes: Colla et al. reported that 18% of Medicare beneficiaries being treated for cancer received chemotherapy within 14 DOD; a 20% reduction in this metric was noted among those who died of cancer between 2006 and 2007 after the implementation of the Medicare Modernization Act.¹⁸

Our study has several limitations. First, our data are reflective of care patterns in a specific subset of RMHNSCC patients at a single, tertiary referral center. Although less likely to be representative of the current RMHNSCC population, patients who did not receive ICI were not included and EOLHCU in these patients is unknown. Similarly, the temporal changes in EOLHCU with the introduction of ICI are unexplored and limited by the relatively recent collection of EOLHCU data.

Oncologic therapy and health care utilization outside our system was not captured in this dataset, including that of patients who died after transferring care outside our institution. Second, our insight into the granularity of end-of-life decision making is limited by retrospective analysis. Understanding associations between potentially modifiable patient, physician, treatment, and institutional factors influencing EOLHCU is critical to creating effective policies that aim at improving these metrics. Related to this, whether the increased rate of ACP documentation was, in fact, a consequence of ED or inpatient admission is difficult to establish.

Third, our exploratory comparison to the TM cohort must be interpreted cautiously and viewed as hypothesis-generating. Although patients with advanced thoracic malignancies also have poor prognosis and often receive ICI, they represent a heterogeneous group with unknown treatment characteristics. Finally, whether or not hospitalization or ER utilization contributes to improved symptom control and quality of life (QOL) was not examined.

Conclusion

The ICI-treated RMHNSCC represents a patient population with higher rates of health care utilization at end of life, suggesting above-average symptom burden. Our observations merit further investigation into interventions and institutional policies that can enhance quality of life and reduce EOLHCU in this expanding population.

Footnotes

Authors' Contributions

All authors certify that they have participated in this work. The article was conceptualized by C.P.R. and primarily interpreted and authored by C.C. and C.P.R. J.M.V. and Q.W. contributed to methodology and analysis. V.H. assisted with data collection. R.S.-D., C.S.B., S.L., B.B., N.D.F., J.J.H., G.E.L., J.J.L., U.P., R.G.M., and K.D.E. all reviewed the article and provided significant revisions. This work has been submitted solely to this journal and is not published or under review elsewhere.

Funding Information

This research was supported by the University of Washington department of Internal Medicine and the Seattle Cancer Care Alliance in Seattle, WA. There was no external funding source.

Author Disclosure Statement

No competing financial interests exist.

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