Oncologic Significance of Therapeutic Delays in Oral Cavity Cancer: A Canadian Multi-Center Study

Presentation: S082
Topic: Oral Cavity
Type: Oral
Date: Sunday, July 9, 2023
Session: 1:45 PM - 3:15 PM Oral Cavity Session 1
Authors: Gabriel S Dayan1; Houda Bahig, MD, PhD2; Stephanie Johnson-Obaseki, MD, MPH3; Antoine Eskander, MD, ScM4; Xinyuan Camilla Hong, MD3; Shamir Chandarana, MD, MSc5; John R de Almeida, MD, MSc6; Anthony C Nichols, MD7; Michael Hier, MD8; Mathieu Belzile, MD, DMD9; Marc Gaudet, MD, MSc10; Joseph Dort, MD, MSc5; T Wayne Matthews, MD5; Robert Hart, MD5; David P Goldstein, MD, MSc6; Christopher Yao, MD6; Ali Hosni, MD, PhD11; Danielle MacNeil, MD, MSc7; James Fowler, MD7; Alex M Mlynarek, MD, MSc8; Gregoire Morand, MD8; Khalil Sultanem, MD12; Tareck Ayad, MD1; Kevin Higgins, MD, MDs4; Carlos Khalil4; Mark Khoury4; Anastasios Maniakas, MD, PhD13; Bernard Fortin, MD, MSc14; Apostolos Christopoulos, MD, MSc1
Institution(s): 1Department of Otolaryngology-Head and Neck Surgery, Centre Hospitalier de l'Université de Montréal (CHUM), University of Montreal, Montreal, Quebec, Canada; 2Department of Radiation Oncology, Centre Hospitalier de l'Université de Montréal (CHUM), University of Montreal, Montreal, Quebec, Canada; 3Department of Otolaryngology-Head and Neck Surgery, University of Ottawa, Ottawa, Ontario, Canada; 4Department of Otolaryngology-Head and Neck Surgery, Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario, Canada; 5Department of Otolaryngology-Head and Neck Surgery, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; 6Department of Otolaryngology-Head and Neck Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada; 7Department of Otolaryngology-Head and Neck Surgery, London Health Sciences Centre, Western University, London, Ontario, Canada; 8Department of Otolaryngology-Head and Neck Surgery, Jewish General Hospital, McGill University, Montreal, Quebec, Canada; 9Department of Otolaryngology-Head and Neck Surgery, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, Quebec, Canada; 10Department of Radiation Oncology, University of Ottawa, Ottawa, Ontario, Canada; 11Department of Radiation Oncology, University Health Network, University of Toronto, Toronto, Ontario, Canada; 12Department of Radiation Oncology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada; 13Department of Otolaryngology-Head and Neck Surgery, MD Anderson Cancer Center, University of Texas, Houston, Texas, United States; 14Department of Radiation Oncology, Maisonneuve Rosemont Hospital, University of Montreal, Montreal, Quebec, Canada

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

Objectives: To report treatment delays for OCC patients in Canada. Secondarily, to evaluate the impact of treatment delays on overall survival (OS).

Methods: A retrospective analysis was conducted using a Pan-Canadian multicenter cohort of OCC patients who underwent surgery and adjuvant radiation therapy from 2005 to 2018. Treatment intervals evaluated were: surgery to initiation of post-operative radiation therapy (S-PORT) and radiation therapy interval (RTI). The exposure variables were prolonged intervals, respectively defined as index S-PORT>42 days and RTI>46 days. Patient demographics, Charlson Comorbidity Index (CCI), smoking status, alcohol status, and pathological staging were also considered. Univariate (logrank and Kaplan-Meier) and multivariate (cox regression) analyses were performed to determine associations with OS.

Results: Amongst seven Canadian academic centers, 1,376 patients were included, with a median follow-up of 33 months. Median S-PORT was 56 days (interquartile range (IQR) 46-68), with 1,107 (80%) patients waiting >42 days, and median RTI was 43 days (IQR 41-47), with 355 (26%) patients waiting >46 days. There was a significant variation in treatment time intervals between institutions for S-PORT (P<0.01) and RTI (P<0.01). 3-year OS was 68%. In univariate analysis, patients with prolonged S-PORT had worse survival at 3 years (66% vs 77%; P<0.001), whereas RTI (P=0.51) was not associated with OS. Other factors associated with OS were age (P<0.01), CCI (P=0.04), alcohol status (P<0.01), T stage (P=0.03), N stage (P<0.01) and institution (P<0.01). Sex and smoking status were not significant. In the multivariate model, prolonged S-PORT remained an independent predictor of OS (hazard ratio 1.34; 95% confidence interval, 1.03-1.75).

Conclusions: For OCC patients requiring surgery and adjuvant radiation therapy, initiation of radiation therapy within 42 days from surgery is associated with better survival. However, in Canada, only a minority complete S-PORT within the recommended delays, whereas most have an appropriate RTI. An inter-institution variation exists 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 towards achieving timely completion of S-PORT.

Treatment intervals stratified by center
Center SPORT, median (IQR) P RTI, median (IQR) P
Overall (N=1376) 56 (46-68) <0.01 43 (41-47) <0.01
A (N=136) 64 (53-77)   44 (42-48)  
B (N=195) 61 (42-76)   43 (31-61)  
C (N=365) 54 (42-66)   44 (42-47)  
D (N=221) 61 (52-69)   44 (42-46)  
E (N=194) 49 (41-58)   42 (38-45)  
F (N=205) 54 (47-63)   42 (42-43)  
G (N=60) 64 (55-77)   40 (35-44)