Oncologic Significance of Therapeutic Delays in Patients With Oral Cavity Cancer

This cohort study reports treatment delays for patients with oral cavity cancer in Canada and evaluates the outcome of treatment delays on overall survival.

Key Points

Question

In patients with oral cavity cancer, what is the prevalence of treatment delays, and what are the oncologic outcomes of such delays?

Findings

In this Canadian multicenter cohort study including 1368 patients, 80% of patients had prolonged times to initiation of postoperative radiation therapy. Delays in initiating radiation therapy were associated with worse overall survival and disease-free survival.

Meaning

Efforts and resources should be directed toward achieving timely initiation of radiation therapy, as this may represent an effective strategy for improving oncologic outcomes in patients with oral cavity cancer.

Abstract

Importance

Oral cavity cancer often requires multidisciplinary management, subjecting patients to complex therapeutic trajectories. Prolonged treatment intervals in oral cavity cancer have been associated with poor oncological outcomes, but there has yet to be a study investigating treatment times in Canada.

Objective

To report treatment delays for patients with oral cavity cancer in Canada and evaluate the outcomes of treatment delays on overall survival.

Design, Setting, and Participants

This multicenter cohort study was performed at 8 Canadian academic centers from 2005 to 2019. Participants were patients with oral cavity cancer who underwent surgery and adjuvant radiation therapy. Analysis was performed in January 2023.

Main Outcomes and Measures

Treatment intervals evaluated were surgery to initiation of postoperative radiation therapy interval (S-PORT) and radiation therapy interval (RTI). The exposure variables were prolonged intervals, respectively defined as index S-PORT greater than 42 days and RTI greater than 46 days. Patient demographics, Charlson Comorbidity Index, smoking status, alcohol status, and cancer staging were also considered. Univariate (log rank and Kaplan-Meier) and multivariate (Cox regression) analyses were performed to determine associations with overall survival (OS).

Results

Overall, 1368 patients were included; median (IQR) age at diagnosis was 61 (54-70) years, and 896 (65%) were men. Median (IQR) S-PORT was 56 (46-68) days, with 1093 (80%) patients waiting greater than 42 days, and median (IQR) RTI was 43 (41-47) days, with 353 (26%) patients having treatment time interval greater than 46 days. There were variations in treatment time intervals between institutions for S-PORT (institution with longest vs shortest median S-PORT, 64 days vs 48 days; η² = 0.023) and RTI (institution with longest vs shortest median RTI, 44 days vs 40 days; η² = 0.022). Median follow-up was 34 months. The 3-year OS was 68%. In univariate analysis, patients with prolonged S-PORT had worse survival at 3 years (66% vs 77%; odds ratio 1.75; 95% CI, 1.27-2.42), whereas prolonged RTI (67% vs 69%; odds ratio 1.06; 95% CI, 0.81-1.38) was not associated with OS. Other factors associated with OS were age, Charlson Comorbidity Index, alcohol status, T category, N category, and institution. In the multivariate model, prolonged S-PORT remained independently associated with OS (hazard ratio, 1.39; 95% CI, 1.07-1.80).

Conclusions and Relevance

In this multicenter cohort study of patients with oral cavity cancer requiring multimodal therapy, initiation of radiation therapy within 42 days from surgery was associated with improved survival. However, in Canada, only a minority completed S-PORT within the recommended time, whereas most had an appropriate RTI. An interinstitution variation existed in terms of treatment time intervals. Institutions should aim to identify reasons for delays in their respective centers, and efforts and resources should be directed toward achieving timely completion of S-PORT.

Introduction

Cancer treatment delays have been associated with increased mortality for various cancer types.¹ This is particularly true for oral cavity squamous cell carcinoma (OCSCC), which often requires multimodal management, including surgery, radiation therapy, and systemic therapy. Delays across any step of the therapeutic timeline have been associated with poor oncologic outcomes.^{2,3,4,5,6,7,8} The National Comprehensive Cancer Network (NCCN) recommends a surgery to initiation of postoperative radiation therapy interval (S-PORT) within 42 days and duration of radiation therapy interval (RTI) between 42 and 46 days for head and neck cancer (HNC).⁹ Furthermore, the American Head and Neck Society and the Commission on Cancer have adopted timely completion of S-PORT as the first quality metric for HNC.¹⁰ Despite this, population database studies in the US have shown that most patients with HNC do not complete treatment without delays.^5,11 However, to our knowledge, there has yet to be a study investigating treatment times and adherence to NCCN guidelines for HNC in Canada, nor the outcomes of treatment delays within the Canadian public health care system. Thus, the aim of this study is to report treatment delays for patients with OCSCC in Canada and to evaluate the outcomes of treatment delays on overall survival (OS) and disease-free survival (DFS).

Methods

This study was conducted as part of the Canadian Head & Neck Collaborative Research Initiative. The institutional review boards at all participating institutions approved this study and waived the need for informed consent owing to the use of deidentified data. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines were followed.

Design and Participants

A retrospective analysis was conducted using a pan-Canadian, multicenter cohort of patients with OCSCC. Inclusion criteria were patients aged 18 years or older, diagnosed with OCSCC, who underwent primary curative-intent surgical resection followed by adjuvant radiation therapy, with or without systemic adjuvant chemotherapy or immunotherapy. Data were collected on patients treated between 2005 and 2019, and analysis was performed in January 2023. There were 8 participating Canadian academic institutions: Centre Hospitalier de l’Université de Montréal, Centre Hospitalier Universitaire de Sherbrooke, London Health Sciences Center, McGill University Jewish General Hospital, Ottawa Cancer Center, Princess Margaret Cancer Center, Sunnybrook Health Sciences Center, and University of Calgary Foothills Medical Center. Patients with missing timeline data were excluded. Patients treated with neoadjuvant radiation therapy or brachytherapy were excluded. The inclusion and exclusion of patients is presented in a summarized flow diagram, which can be found in the eFigure in Supplement 1.

Treatment intervals evaluated were S-PORT and RTI; S-PORT was defined as time from surgery to start of adjuvant radiation therapy, and RTI was defined as time from start to end of radiation therapy. Prolonged S-PORT and prolonged RTI were respectively defined as an index S-PORT greater than 42 days and an index RTI greater than 46 days, as recommended by the NCCN.⁹ Patients with S-PORT 14 days or less or greater than 180 days were excluded. Clinicopathological data were collected, including age, sex, Charlson Comorbidity Index, smoking status, pack-years smoked, alcohol status, prior HNC, and TNM stage (based on American Joint Committee on Cancer [AJCC] edition corresponding to the year when it was staged).¹²

The primary outcome of interest was OS, defined as time from surgery to time of last follow-up or death from any cause. The secondary outcome was DFS, defined as time from surgery to time of last follow-up, locoregional failure, distant metastases, or death, whichever came first.

Statistical Analysis

Statistical analysis was performed using SPSS, version 28 (IBM Corporation) and SAS, version 9.4 (SAS Institute) statistical software. Descriptive characteristics are presented as mean (SD) or median (IQR) for continuous parameters and frequency distributions (number and proportion) for categorical parameters for all patient demographics and baseline characteristics. Treatment interval times were compared across different institutions and assessed the effect size of institutions using eta squared (η²) (η² < 0.01 indicates a very small effect size, 0.01 ≤ η² < 0.06 represents a small effect size, 0.06 ≤ η² < 0.14 indicates a medium effect size, and η² ≥ 0.14 reflects a large effect size).¹³ Overall survival at 3 years was estimated using the Kaplan-Meier method. Univariate Cox regression model was used to identify factors associated with OS and DFS. Multivariate Cox regression analysis was performed to explore the independent association between these parameters and outcomes. Variables showing a noteworthy statistical association in the univariate model as indicated by a P < .20 were included in the multivariate model. Stepwise selection methods were used to develop the final models. An α level of .05 was used as the cutoff for statistical significance in the multivariable analysis.

To identify ideal cutoff points of S-PORT and RTI, a series of Kaplan-Meier analyses were produced with stratifications at 5, 6, 7, 9, and 10 weeks for S-PORT and at 6, 7, 9, and 10 weeks for RTI, for both OS and DFS. The number of weeks that maximized the hazard ratio (HR) statistic were selected. A second series of Kaplan-Meier analyses were produced with cut-off points being each day corresponding to the selected week to identify the specific number of days for each treatment interval that maximized the HR.

Results

The study population consisted of 1368 patients (median [IQR] age at diagnosis, 61 [54-70] years; 896 [65%] male) who received surgery and adjuvant radiation therapy among a total cohort of 4506 (30.3%) patients with OCSCC from the Canadian Head & Neck Collaborative Research Initiative Oral Cavity Cancer Database, treated at 8 Canadian centers from 2005 to 2019. Clinicopathological description of the cohort is summarized in Table 1.

Table 1. Clinicopathological and Treatment Characteristics of the Study Cohort.

Characteristic	No. (%) (n = 1368)
Age at diagnosis
Median (IQR), y	61 (54-70)
>65 y	497 (36)
Sex
Female	472 (35)
Male	896 (65)
Charlson Comorbidity Index score
0-1	338 (26)
2-3	449 (33)
≥4	543 (41)
Tobacco smoking status
Never	387 (28)
Previous	390 (29)
Current	582 (43)
Pack-years, median (IQR)	35 (20-45)
Alcohol use
Never	730 (54)
Previous	207 (15)
Current	414 (31)
Oral cavity subsite
Oral tongue	616 (45)
Floor of mouth	247 (18)
Buccal	119 (9)
Retromolar trigone	89 (7)
Hard palate	23 (2)
Mucosal lip	19 (1)
Mandibular alveolus	196 (14)
Maxillary alveolus	58 (4)
Pathologic T category
T1	198 (15)
T2	444 (33)
T3	243 (18)
T4	473 (35)
Pathologic N category
N0	570 (43)
N1	221 (16)
N2	489 (36)
N3	88 (6)
Radiation therapy
Dose, median (IQR), Gy	60 (60-66)
Fractions, median (IQR)	30 (30-33)
Systemic chemotherapy	403 (30)
S-PORT
Median (IQR), d	56 (46-68)
>42 d	1093 (80)
RTI
Median (IQR), d	43 (41-47)
>46 d	353 (26)

Abbreviations: RTI, radiation therapy interval; S-PORT, surgery to initiation of postoperative radiation therapy interval.

Description of Intervals

The mean (SD) and median (IQR) overall S-PORT interval was 60.1 (27.3) days and 56 (46-68) days, respectively. Eighty percent (n = 1093) of patients initiated radiation therapy more than 42 days after surgery. Interinstitution variations in S-PORT (η² = 0.023) are detailed in Table 2. All centers had a median S-PORT of more than 42 days. The institution with longest delays had a median (IQR) S-PORT of 64 (53-78) days compared with 48 (40-59) days for the institution with the shortest S-PORT. The mean (SD) and median (IQR) RTI duration of the cohort was 43.4 (13.0) days and 43 (41-47) days, respectively, with a small variation between centers (η² = 0.022) (Table 2). None of the centers had a median RTI of more than 46 days (range, 40-44 days). A total of 353patients (26%) had a prolonged RTI.

Table 2. Treatment Intervals Stratified by Institution.

Center	S-PORT, median (IQR), d	η2	RTI, median (IQR), d	η2
1 (n = 131)	64 (53-78)	0.023	44 (42-48)	0.022
2 (n = 57)	64 (53-77.5)		40 (35-45.5)
3 (n = 195)	61 (42-76)		43 (31-61)
4 (n = 221)	61 (52-69)		44 (42-46)
5 (n = 193)	54 (47-63)		42 (42-43)
6 (n = 362)	54 (42-66)		44 (42-47)
7 (n = 194)	49 (41-58)		42 (38-45.25)
8 (n = 15)	48 (40-59)		40 (37-42)

Abbreviations: RTI, radiation therapy interval; S-PORT, surgery to initiation of postoperative radiation therapy interval.

Optimal Cutoff for Treatment Delays

For S-PORT, the cutoff that maximized the HR statistic was 42 days for both OS (HR, 1.43; 95% CI, 1.11-1.84) and DFS (HR, 1.35; 95% CI, 1.09-1.67). For RTI, we identified cutoff points at 49 days for OS (HR, 1.30; 95% CI, 1.02-1.65) and 51 days for DFS (HR, 1.12; 95% CI, 0.90-1.39).

Overall Survival

There was a median follow-up of 34 months. The OS for all patients at 3 years was 68%. Patients with prolonged S-PORT (>42 days) had a 3-year OS of 66%, which was worse than patients with S-PORT of 42 days or less, who had an OS of 77% (odds ratio [OR], 1.75; 95% CI, 1.27-2.42) (Figure). Patients with RTI of 46 days or less had a 3-year OS of 69% compared with 67% for those with a RTI greater than 46 (OR, 1.06; 95% CI, 0.81-1.38). The OS at 3 years was 69% for patients with RTI of 49 days or less compared with 61% for patients with RTI greater than 49 days (OR, 1.45; 95% CI, 1.05-2.00). Univariate and multivariate Cox regression analyses for OS outcome are detailed in Table 3. In the univariate model, S-PORT greater than 42 days (HR, 1.43; 95% CI, 1.11-1.84) and RTI greater than 49 days (HR, 1.31; 95% CI, 1.03-1.66) were associated with OS. In the multivariate model, prolonged S-PORT remained independently associated with OS (HR, 1.39; 95% CI, 1.07-1.80). Other clinical and pathological variables associated with OS and included in the multivariable model are detailed in Table 3.

Figure. Kaplan-Meier Survival Curves Stratified by Treatment Intervals.

Kaplan-Meier curves of overall survival (OS) stratified at (A) S-PORT greater than 42 days, (B) RTI greater than 46 days, and (C) RTI greater than 49 days. Kaplan-Meier curves of disease-free survival (DFS) stratified at (D) S-PORT greater than 42 days, (E) RTI greater than 46 days, and (F) RTI greater than 51 days. RTI indicates radiation therapy interval; S-PORT, surgery to postoperative radiation therapy interval.

Table 3. Univariate and Multivariate Regression Results for Overall Survival.

Variable	HR (95% CI)
	Univariate	Multivariate
Age
Continuous (years)	1.01 (1.01-1.03)	NA
>65 y	1.50 (1.25-1.81)	1.53 (1.26-1.87)
Sex
Female	1 [Reference]	NA
Male	1.08 (0.89-1.31)	NA
Smoking status
Never	0.93 (0.74-1.16)	NA
Previous	1.10 (0.89-1.36)	NA
Current
Alcohol drinking
Never	0.71 (0.58-0.87)	0.76 (0.62-0.93)
Previous	0.80 (0.60-1.06)	0.82 (0.61-1.09)
Current	1 [Reference]	1 [Reference]
Charlson Comorbidity Index
0-1	1 [Reference]	1 [Reference]
2-3	1.63 (1.25-2.12)	1.32 (0.99-1.75)
≥4	2.12 (1.64-2.74)	1.28 (0.96-1.71)
Tumor classification
T1	1 [Reference]	1 [Reference]
T2	1.15 (0.85-1.54)	1.12 (0.83-1.51)
T3	1.26 (0.91-1.76)	1.17 (0.83-1.65)
T4	1.38 (1.04-1.85)	1.41 (1.05-1.90)
Lymph node status
N0	1 [Reference]	1 [Reference]
N1	1.71 (1.28-2.28)	1.73 (1.27-2.35)
N2	3.04 (2.44-3.80)	2.99 (2.36-3.79)
N3	4.38 (3.09-6.23)	4.47 (3.11-6.41)
S-PORT
Continuous (days)	1.00 (1.00-1.01)	NA
> 42 d	1.43 (1.11-1.84)	1.39 (1.07-1.80)
RTI
Continuous (days)	1.00 (0.99-1.01)	NA
>46 d	1.06 (0.87-1.31)	NA
>49 d	1.31 (1.03-1.66)	1.28 (0.98-1.68)

Abbreviations: HR, hazard ratio; NA, not applicable; RTI, radiation therapy interval; S-PORT, surgery to postoperative radiation therapy interval.

Disease-Free Survival

The DFS for all patients at 3 years was 59%. Patients with prolonged S-PORT had a 3-year DFS of 57%, which was worse than patients with S-PORT of 42 days or less, who had a DFS of 67% (OR, 1.65; 95% CI, 1.23-2.20) (Figure). There was comparable 3-year DFS for patients with RTI greater than 46 days and 46 days or less (59% vs 59%; OR, 1.03; 95% CI, 0.80-1.32). Patients with RTI 51 days or less had 3-year DFS of 59% compared with 57% for patients with RTI greater than 51 (OR, 1.18; 95% CI, 0.84-1.66). Univariate and multivariate Cox regression analyses for DFS outcome are detailed in Table 4. In the univariate model, prolonged S-PORT (HR, 1.34; 95% CI, 1.09-1.66) was associated with worse DFS. For longer RTI at cutoffs 46 days (HR, 1.08; 95% CI, 0.90-1.29) and 51 days (HR, 1.19; 95% CI, 0.92-1.55), there were trends toward worse DFS in this study cohort, though no definitive conclusions can be made. On multivariable analysis, prolonged S-PORT was independently associated with an increased hazard of DFS (HR, 1.29; 95% CI, 1.04-1.61). Other clinical and pathological variables associated with OS and included in the multivariable model are detailed in Table 4.

Table 4. Univariate and Multivariate Regression Results for Disease-Free Survival.

Variable	HR (95% CI)
	Univariate	Multivariate
Age
Continuous (years)	1.01 (1.01-1.02)	NA
>65 y	1.39 (1.18-1.63)	1.35 (1.13-1.61)
Sex
Female	1 [Reference]	NA
Male	1.12 (0.94-1.32)	NA
Smoking status
Never	1.10 (0.91-1.33)	1.16 (0.98-1.58)
Previous	1.19 (0.99-1.44)	1.12 (0.92-1.37)
Current	1 [Reference]	1 [Reference]
Alcohol drinking
Never	0.80 (0.67-0.95)	0.77 (0.63-0.94)
Previous	0.80 (0.62-1.03)	0.84 (0.65-1.09)
Current	1 [Reference]	1 [Reference]
Charlson Comorbidity Index
0-1	1 [Reference]	1 [Reference]
2-3	1.19 (0.95-1.49)	1.03 (0.82-1.30)
≥4	1.74 (1.41-2.14)	1.18 (0.93-1.50)
Tumor classification
T1	1 [Reference]	1 [Reference]
T2	1.16 (0.90-1.50)	1.13 (0.87-1.46)
T3	1.32 (0.99-1.76)	1.20 (0.89-1.62)
T4	1.43 (1.11-1.84)	1.44 (1.10-1.87)
Lymph node status
N0	1 [Reference]	1 [Reference]
N1	1.49 (1.17-1.91)	1.51 (1.16-1.96)
N2	2.48 (2.06-2.98)	2.41 (1.97-2.95)
N3	3.13 (2.28-4.30)	3.07 (2.22-4.26)
S-PORT
Continuous (days)	1.00 (1.00-1.00)	NA
>42 d	1.34 (1.09-1.66)	1.29 (1.04-1.61)
RTI
Continuous (days)	1.00 (1.00-1.01)	NA
>46 d	1.08 (0.90-1.29)	NA
>51 d	1.16 (0.92-1.47)	1.21 (0.95-1.54)

Abbreviations: HR, hazard ratio; NA, not applicable; RTI, radiation therapy interval; S-PORT, surgery to postoperative radiation therapy interval.

Discussion

We present a multicenter cohort study from 8 academic reference institutions in Canada investigating oncologic outcomes of treatment delays in oral cavity cancer. We demonstrated that initiation of radiation therapy within 42 days from surgery was associated with improved OS and DFS in OCSCC. In Canada, only a minority of patients with OCSCC completed S-PORT within the recommended delays, while most had an appropriate RTI. Finally, an interinstitution variation existed in terms of treatment time intervals.

This study adds to the existing body of literature on treatment delays in HNC by giving a Canadian perspective. By demonstrating that the majority of patients with OCSCC in Canada experience prolonged S-PORT, our findings suggest that there is a pressing need to address delays in treatment for this patient population, as most patients could benefit from improvements to this metric. Specifically, 80% of patients did not complete S-PORT on time, and every institution in our study had a median S-PORT over the recommended time. Prior works using National Cancer Database data have explored rates of adherence to NCCN HNC guidelines in the US.^5,11 They found that 55%¹¹ to 75%⁵ of patients treated with surgery and adjuvant radiation therapy had prolonged S-PORT time and that delays are worsening over time. On the other hand, our study revealed that adherence to RTI recommendations was very good in Canadian institutions, with 43 days as both the median and mean RTI, and all institutions in the cohort having a median less than 46 days. Comparatively, 1 National Cancer Database study reported a mean RTI of 50 days,⁵ slightly higher than the NCCN-recommended 42 to 46 days,⁹ and another study reported that only 22% of patients had an “accelerated RTI,” defined as less than 47 days.⁸

Furthermore, our results reinforce the existing body of literature demonstrating an association between prolonged time to initiation of radiation therapy and oncologic outcomes in HNC and validate that this association holds true in the Canadian universal health care system. We were able to identify a cutoff at 42 days for S-PORT interval where patients start to experience worse survival, which is in accord with NCCN recommendations (≤6 weeks)⁹ and findings from prior authors.^3,5

Most of the works investigating S-PORT in HNC found that prolonged intervals were associated with worse OS.^{1,3,4,5,14,15,16} Ho et al⁵ reported a 5-year OS of 67% when S-PORT was 40 days or less compared with 57% from 40 to 70 days and 50% when greater than 70 days. Similarly, Graboyes et al³ reported worse OS when S-PORT was greater than 6 weeks (60% vs 71%). These results are in accord with our findings of an approximate 10% difference in 3-year OS (77% vs 66%) between patients who completed S-PORT by 42 days and those who did not. Conversely, Fujiwara et al¹⁷ did not find S-PORT to be associated with OS, but unlike other authors, “prolonged S-PORT” was defined as greater than 64 days, which is more than 50% longer than that recommended by the NCCN. Ho et al⁵ performed a restricted cubic spline analysis for S-PORT and identified cutoff points for mortality risk at 40 days and 70 days.

Prior reports have been heterogeneous with respect to the association between oncologic outcomes and RTI. Although Shaikh et al⁸ found a large association between RTI and OS for patients receiving definitive radiation therapy, they found no association between RTI and OS for patients receiving adjuvant radiation therapy. On the other hand, Ho et al⁵ and Fujiwara et al¹⁷ found medium to large associations between RTI and OS for patients receiving postoperative radiation therapy. Ho et al⁵ used a cubic spline analysis to derive a cutoff at 55 days for RTI.

In our study, an RTI greater than 49 days was associated with worse OS. However, following multivariate analysis, no definitive conclusion was able to be made with respect to the association between RTI and OS or DFS. This may be because Canadian institutions adhered to NCCN-recommended delays for RTI.⁹ Indeed, the recommended range is 42 to 46 days, and in our study cohort, the median (IQR) RTI was 43 (41-47) days, with all institutions having a median RTI of less than 46 days. This may have limited our ability to draw statistical conclusions with respect to the associations between RTI delays and survival outcomes. The difference of RTI delays in Canadian institutions compared with other studies may be due to inherent differences in the Canadian health care system. Further studies may be necessary to better understand the association between RTI delays and survival outcomes in different health care systems.

Differences between the US and Canadian health care systems can have important implications for the care of patients with HNC. In Canada, health care is publicly funded and offers universal coverage to all Canadian citizens and residents. Care is administered by public provincial health insurance programs and must cover all medically necessary hospital, diagnostic, and physician services. In contrast, the health care system in the US operates on a combination of private and public insurance. This fragmented structure often leads to disparities in coverage and access to care. Indeed, National Cancer Database studies have highlighted that, for patients with HNC, insurance status is associated with treatment delays and oncologic outcomes.^5,7,18 While universal health care coverage mitigates some barriers, socioeconomic factors can still influence HNC outcomes in Canadian patients. In a Canadian HNC cohort, Noel et al¹⁹ revealed that lower household income was associated with worse oncologic outcomes and health status. Regarding dental insurance, coverage in Canada varies by province. Many provinces offer publicly funded insurance programs that cover dental care services related to oral cavity cancer and associated radiation therapy.²⁰ For instance, Quebec’s Adult Oral Radiation Oncology program covers examinations, basic fillings, extractions, and preventive services before and up to 12 months after radiation treatment.²⁰ On the other hand, in the US, Medicare provides coverage for initial dental services required for radiation therapy, including dental extraction and pre-extraction examination, but other dental services and follow-up care are not covered.²¹

There has been a shift toward a multimodal approach in the care of HNC, with several studies suggesting that multidisciplinary care leads to better cancer outcomes.^22,23 However, this shift has not been able to translate into decreased mortality rates in national cancer statistics reports.^24,25,26 Some authors propose that this may be in part due to the fact that multidisciplinary care comes with the trade-off of prolonged treatment delays, which may contribute to poorer outcomes.^5,27 Indeed, in recent years, survival rates for HNCs have only shown marginal to nonexistent improvements. The Canadian Cancer Society’s 2021 statistics report revealed a 64% 5-year survival rate for oral cavity cancer, with a nonsignificant annual percentage change in age-standardized mortality from 2010 to 2019 compared with a 2.1 annual percentage change from 1984 to 2010.²⁴ Similarly, in the US, the National Cancer Institute reported a 68.5% 5-year survival rate in 2020 and no change in mortality since 2005.²⁵ Although quality-of-life survivorship has improved, mortality rates remain stagnant for HNC. However, with such an important association between treatment times and oncologic outcomes, identifying effective interventions to decrease the rates of treatment delays may represent a potential opportunity for decreasing mortality in these patients and be a paradigm shift in HNC care in the next years.

The literature on barriers to timely completion of treatment intervals in HNC is growing. Qualitative interview-based studies have identified several recurring themes that may hinder the timely completion of S-PORT. These include inadequate education about S-PORT, poor care coordination and communication among multidisciplinary team members, travel burden, low social and financial support, and process delays.^28,29 Quality improvement initiatives have been proposed to address these barriers and have demonstrated promising results. Voora et al³⁰ implemented pathway order sets and assigned a patient navigator to coordinate timely radiation therapy and referrals. This intervention led to increased adherence to completion of S-PORT within 42 days. Similarly, Graboyes et al³¹ proposed a multilevel intervention encompassing patient education, travel support, care plans, referral tracking, and organizational restructuring. Divi et al³² put forth 12 interventions targeting delayed dental evaluation, delayed radiation oncology consultation, and improved coordination and communication with patients.

Limitations

The current study has several limitations. First, it is retrospective in nature, increasing the probability of missing data or data capture errors. Patients with missing timeline data were excluded, and reasons for missing data may not have been random, leading to a potential overestimation or underestimation of the prevalence of delayed treatments. It was not possible to restage all patients originally staged using a previous edition of the AJCC staging manual to the 8th edition¹² because parameters such as depth of invasion and extranodal extension were missing for many of the patients treated in earlier years of the study period. For similar reasons, these parameters were not included in the multivariate model. Also, important variables such as race, ethnicity, performance status, free flap, length of stay, discharge destination, and margin status were not captured but may be associated with both treatment delays and outcomes. The study was conducted in Canadian academic institutions, and the results may not be generalizable to different health care systems or nonacademic centers. Despite these limitations, the study has several strengths, including its large multicenter cohort of patients with HNC spanning over 10 years, all of whom were treated at expert reference centers in Canada.

Another limitation of this study is that it did not explore reasons for prolonged treatment times, which likely vary across institutions and include factors such as postoperative complications, nonadherence, delays in pathology reports, delays in consulting specialists (radiation oncology and medical oncology), or delays in preradiation dental extractions. We believe there would added value for institutions to perform quality improvement studies in their respective centers to identify reasons for delays and target strategies to achieve timely completion of S-PORT.³² This may represent an effective avenue for improving survival outcomes in patients with OCSCC.

Conclusions

In this multicenter cohort study of patients with OCSCC requiring surgery and adjuvant radiation therapy in Canada, failure to initiate adjuvant radiation therapy within 6 weeks, as recommended by the NCCN, was independently associated with worse OS and DFS. Most patients in Canada and the US do not fall within this less-than-6-week category. Unlike patient and tumor-intrinsic factors associated with mortality in HNC, treatment delays represent a modifiable risk factor and should be prioritized by the multidisciplinary teams.

Supplement 1.

eFigure. Patient selection flow diagram

Supplement 2.

Data Sharing Statement