Proactive Risk-based Optimization & Notifications for Treatment & Outcomes (PRONTO) in Head & Neck Cancer: A Strategy to Reduce Delays From Surgery to Post-Operative Adjuvant Therapy in Head and Neck Cancer
Phase: NA
Conditions: Oral Cancer , Oral Squamous Cell Carcinoma, Oral Cavity Cancer, Head &Amp;Amp; Neck Squamous Cell Carcinoma, Larynx Squamous Cell Carcinoma
Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

 
 
 
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Title 
Proactive Risk-based Optimization & Notifications for Treatment & Outcomes in 
Head & Neck Cancer (PRONTO-HN): A Strategy to Reduce Delays from Surgery to 
Post-Operative Adjuvant Therapy in Head and Neck Cancer 
 
Principal Investigators:  
Apostolos Christopoulos, MD, MSc (Departement of surgery, Division of Otolaryngology – head & neck 
surgery, Centre Hospitalier de l’Université de Montréal, Université de Montréal, Montréal, Québec) 
 
Houda Bahig, MD, PhD (Departement of radiology, radiation oncology & nuclear medicine, Division of 
radiation oncology, Centre Hospitalier de l’Université de Montréal, Université de Montréal, Montréal, 
Québec) 
 
Co-investigator:  
 
Gabriel Dayan, MD (Departement of surgery, Division of Otolaryngology – head & neck surgery, Centre 
Hospitalier de l’Université de Montréal, Université de Montréal, Montréal, Québec) 
 
 
Version  
 
 
Date 
Translated from French (original) to English: 25-07-2025 
Original French version: 11-02-2024 
 
NCT Number 
NCT ID not yet assigned 
Funding 
Azar-Angélil Chair in Head & Neck Oncology 
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Table of Contents 
1. Summary of the Research Protocol 
1.1. Rationale 
1.2. Primary Objective 
1.3. Primary Endpoint 
1.4. Secondary and Tertiary Endpoints 
1.5. Study Design 
1.6. Study Population 
1.7. Data Collection: Variables and Measures 
1.8. Study Conduct and Data Quality 
1.9. Sample Size 
1.10. Study Duration 
1.11. Statistical Analysis 
1.12. Specific Elements Explaining the Study 
2. Introduction 
2.1. Study Rationale 
2.2. Background 
2.3. Benefits and Risks 
3. Objectives and Endpoints 
3.1. Primary Objective 
3.2. Secondary Objectives 
3.3. Tertiary/Exploratory Objectives 
3.4. Primary Endpoint 
3.5. Secondary and Tertiary/Exploratory Endpoints 
4. Methods 
4.1. Study Design and Context 
4.2. Study Population 
4.2.1. Inclusion Criteria 
4.2.2. Exclusion Criteria 
4.2.3. Participant Selection and Recruitment 
4.3. Data Collection: Variables and Measurements 
4.3.1. Study Procedures and Execution 
4.3.2. Intervention or Exposure Variable 
4.3.3. Outcome Variables 
4.3.4. Demographic and Clinical Variables 
4.3.5. Covariates 
4.3.6. Bias Minimization Strategies 
4.4. Statistical Aspects 
4.4.1. Sample Size 
4.4.2. Statistical Analysis 
5. Monitoring and Safety 
6. Ethical Considerations 
7. References 
8. Appendices 
 

 
 
 
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1. Summary of the Research ProtocolRationaleThe optimal management of head and neck 
cancer requires a multidisciplinary approach. Delays in treatment intervals, particularly between 
surgery and post-operative radiotherapy (S-PORT) have been associated with reduced overall 
survival. Preliminary studies by our team have shown that treatment delays are highly prevalent in 
Canada.  
1.2. Primary ObjectiveTo evaluate the impact of enhanced care coordination and an automated alert 
system on S-PORT delays in patients with head and neck cancer requiring multimodal therapy. 
1.3. Primary EndpointProportion of patients with S-PORT ≤ 42 days. 
1.4. Secondary and Tertiary EndpointsOverall survival (OS) 
• 
Locoregional survival (LRS) 
• 
Distant metastasis-free survival (DMFS) 
• 
Disease-free survival (DFS) 
• 
Recurrence-free survival (RFS). 
 
1.5. Study DesignA single-center, quasi-experimental interrupted time-series pilot study. Phase 1: 
Group A (control) – pre-implementation of the PRONTO-HN system. Phase 2: Group B – following 
implementation of the PRONTO-HN system.  
1.6. Study PopulationPatients with oral cavity or laryngeal squamous cell carcinoma treated with 
primary intention surgery at the CHUM. 
1.7. Data Collection: Variables and MeasuresOur newly developed organizational navigation 
system optimizes multidisciplinary team coordination by extracting data from hospital systems and 
sending automatic task-specific reminders and deadlines. Risk stratification is performed using our 
validated pre-operative predictive model for adjuvant therapy need. 
1.8. Study Conduct and Data QualityTo minimize seasonal bias, both study phases span 12 months.  
1.9. Taille d’échantillonWe estimate that 80 patients per year are treated with primary intention 
surgery at the CHUM for oral cavity or laryngeal squamous cell carcinoma. To demonstrate a 
reduction in S-PORT delays from 80% to 50% (α=0.05, β=0.20), a sample size of 38 patients per 
group is needed.  
1.10. Study duration- Control phase: August 2024 – August 2025 
- Intervention phase: September 2025 – September 2026 
1.11. Statistical AnalysisThe statistical analysis will be performed using R statistical software. Patient 
characteristics will be presented as means (standard deviation) or medians (interquartile range) for 
continuous variables, and frequency distributions (number and proportion) for categorical 
variables. Univariate logistic regression will identify covariates associated with prolonged treatment 
intervals. Multivariate logistic regression will explore the independent association between the 

 
 
 
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intervention and treatment intervals, using a combination of univariate regression, expert opinion, 
and variables known from the literature to be associated with treatment delays. 
 

 
 
 
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2. Introduction 
2.1. Study rationaleThe optimal management of head and neck cancers often requires a 
multidisciplinary approach. Several treatment intervals have been described in the head and neck 
cancer literature, including the diagnosis and treatment interval (DTI), surgery to post-operative 
radiation therapy (S-PORT), and radiation therapy interval (RTI). Delays in these intervals could 
negatively impact oncological outcomes and overall survival 1-10.  
 
In a Canadian multicenter study, our team demonstrated an association between SPORT delays and 
oncological outcomes in oral cavity cancer patients, with a reduction of approximately 10% in 3-year 
overall survival 3. Motivated by these findings, our group conducted a subsequent study to identify 
predictors and organizational bottlenecks causing delays in treatment intervals 11. We found that time to 
pre-operative imaging report was associated with prolonged DTI and times to pathology report, to 
maxillofacial consult and to medical oncology consult were associated with prolonged SPORT. Strategies 
targeting these organizational bottlenecks may be effective for shortening treatment time intervals, 
hence representing potential opportunities for improving oncological outcomes in head and neck cancer 
patients. In another follow-up study, our team developed a predictive model using pre-operative data 
for necessitating adjuvant therapy after surgery in this patient population 12. 
 
2.2. BackgroundThe National Comprehensive Cancer Network (NCCN) Guidelines for head & neck 
cancer recommend initiating post-operative radiation therapy within 6 weeks after surgery 13. In a 
recent systematic review and meta-analysis of studies conducted in the United States of America, 
Duckett et al found that delays in initiating PORT within recommended delays occurs in 
approximately 50% of patients 14. Similarly, in our Canadian multicenter study, we had found that it 
was nearly 80% of patients who have prolonged S-PORT interval 3.  
 
This field of research is very quickly growing. The focus is shifting from reporting the prevalence of 
treatment delays and its association with outcomes in head and neck cancer to comprehending the 
obstacles and developing interventions to tackle them. Still, there is limited research exploring 
interventions aimed at reducing treatment delays in head and neck cancer.  
 
Qualitative interview-based studies have identified various obstacles potentially impeding the prompt 
completion of SPORT. These barriers include poor patient education about SPORT, suboptimal care 
coordination and communication among members of the multidisciplinary team, travel challenges, 
inadequate social and financial support, and process delays 15,16. Through chart reviews and 
departmental discussions at their institution, Divi et al postulated that timely dental extraction, referrals 
to radiation oncology and medical oncology, and patient engagement were important drivers of SPORT 
17. They then proposed twelve interventions aiming to reduce treatment delays. These interventions 
include dental Panorex at new visits, having a coordinator for adjuvant therapy consults, early 
discussions with patients of where adjuvant therapy will take place, etc. After implementing these 
measures (N=56), the percentage of patients completing SPORT in under 42 days went from 62% (21/34) 
to 73% (16/22), though statistical significance was not reported. In another study, Graboyes et al (N = 
15) implemented a comprehensive intervention involving patient education, travel support, care plans, 
referral tracking, and organizational restructuring 18. They demonstrated the feasibility and acceptability 
of the intervention, with 86% of patients in their cohort completing S-PORT in 42 days or less. 
 

 
 
 
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2.3. Benefits and risksThe current study proposes an organizational intervention to improve 
treatment delays for patients with head and neck cancer. Given the increasing amount of evidence 
that prolonged treatment times have a negative impact on overall survival in head and neck cancer 
patients and the fact that most patients in North America do not adhere to recommended 
treatment times 3,19,20, if this study were to be successful it has the potential to improve oncologic 
outcomes in this patient population. Other benefits include improved patient experience. 
Conversely, the proposed study poses no risk for patients. The proposed intervention will help 
healthcare team providers improve collaboration, communication, and coordination, but will not 
directly impact the patient or change the therapeutics received by the patient. 
3. Objectives and endpoints 
3.1. Primary objectiveThe primary objective is to evaluate the impact of an organization navigation, 
care coordination, risk stratification and automated physician alert system on S-PORT delays in 
patients with head & neck cancer requiring multimodal therapy. 
3.2. Secondary objectivesThe secondary objective is to evaluate the impact of an organization 
navigation, care coordination, risk stratification and automated physician alert system on overall 
survival, locoregional survival, distant metastasis-free survival, recurrence-free survival and disease-
free survival time in patients with head & neck cancer requiring multimodal therapy. 
3.3. Primary endpoint, primary outcome measureSurgery to post-operative radiation therapy 
(SPORT - defined as number of days from surgery to initiation of radiation therapy or 
chemoradiation) ≤42 days.  
• 
S-PORT mean 
3.4. Secondary, tertiary / exploratory endpointsOncologic outcomes all defined from time to 
surgery to time of event.  
• 
Overall survival, with events defined as death from any cause. 
• 
Locoregional survival, with events defined as locoregional recurrence (primary site or cervical 
node) or death. 
• 
Distant metastasis-free survival, with events defined as distant metastasis or death.  
• 
Recurrence-Free Survival, with events defined as any recurrence (local, regional, or distant). 
Deaths without recurrence are censored. 
• 
Disease-free survival, with events defined as recurrence (any site) or death. 
 
4. Methods 
4.1. Study design and contextA single center quasi-experimental interrupted chronological series 
pilot study will be used to evaluate a new care coordination intervention (detailed below).  
 
The study will be divided into two phases: firstly, as a control group, consecutive pre-intervention 
eligible patients will be included in Group A. The treatment time intervals will be extracted registered 
from a prospectively maintained database for all cases in Group A (from August 2024 to August 2025). In 
the second phase, the new care coordination system (detailed below) will be introduced (starting 
September 2025 until September 2026). Consecutive eligible patients in this phase will be included 

 
 
 
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in Group B. The treatment time intervals will be prospectively registered for all cases in Group B. The 
study will be performed using an intention-to-treat analysis. Individual patient data will be collected.  
4.2. Study populationPatients with oral cavity and laryngeal squamous cell carcinoma treated with 
primary intention surgery. 
4.2.1. Inclusion criteria 
• 
All adult patients (age 18 or greater). 
• 
Pathologically confirmed oral cavity or laryngeal squamous cell carcinoma. 
• 
Diagnosed from August 2024 to August 2026. 
• 
With planned primary intention surgical resection from August 2024 to September 2026. 
• 
Treated at the Centre Hospitalier de l’Université de Montréal. 
4.2.2. Exclusion criteria 
• 
Patients who do not end up receiving surgery. 
• 
S-PORT > 180 days 
4.2.3. Participant selection or recruitmentPatients from the pre- and post-intervention groups 
come from the same cohort. Patients will be identified at time operative request is made by 
head and neck surgeon (Division of Otolaryngology, Centre Hospitalier de l’Université de 
Montréal). All eligible patients meeting the inclusion and exclusion criteria will be enrolled in the 
study. The investigation involves a quality improvement intervention designed to enhance the 
organization and healthcare administration for the head and neck oncology multidisciplinary 
teams. The participating hospital services, in the post-intervention phase of the study, will adopt 
these practice modifications for all new patients. It is important to note that the intervention 
does not involve a drug, technology, device, or any other intervention that directly reaches the 
patient, and poses no risk to the patients. Consequently, the need for informed consent has 
been waived by the IRB, and all eligible patients will be automatically included. 
4.3. Data collection : variables and measurements 
4.3.1. Study procedures and execution 
 
4.3.2. Intervention or exposure variable 
4.3.2.1. Allocation of interventions and blinding 
Not applicable.  
 
4.3.2.2. Interventions or exposures – Other study designs 
The head and neck cancer team at the CHUM plans to implement the use of a new organisational 
system, independent of this study. This care coordination and organizational navigation system is aimed 
at optimizing the therapeutic trajectory for patients with head and neck cancers. This system facilitates 
collaboration within the multidisciplinary team by extracting relevant data from institutional computer 
systems (OACIS, PACS, MOSAIC, etc.), stratifying patients based on risk of receiving adjuvant treatment 
after surgery and sending various members of the multidisciplinary team automated reminders and 
target dates to complete specific tasks. It is important to note that this system affects members of the 

 
 
 
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multidisciplinary team in that it aims to improve coordination but does not directly impact patients or 
patient care. Norms of care and treatment modalities for patients remain the same.  
 
Specifically, at time of booking operating room request, each patient is inserted in clinical calculator, 
which calculates a risk of requiring adjuvant therapy following surgery using our predictive model12 that 
stratifies patients into low (normal-track) and high (fast-track) risk.  
 
For high-risk patients (fast-track): 
• 
Pre-operative radiation oncology consult done at same time as otolaryngology consult. 
• 
Pre-operative dental consult. 
o If not done (or scheduled) 1 week prior to date of surgery, reminder email sent to 
dentist, radiation oncologist and surgeon.  
• 
Pre-operative medical oncology consult request if any of the following are present: 
o clinical or imaging ENE (matted nodes, invasion of adjacent structures, clinically 
bulky/fixed nodes) 
o invasion of extrinsic muscle of tongue 
o bony invasion 
o involvement of pterygoid space 
o > 4 cm tumor 
• 
Target date for post-operative pathology report set to 14 days post-operatively. 
o On day of surgery, a reminder email is sent to pathology department coordinator, 
pathologist, radiation oncologist and surgeon. 
o 5 days before target, a reminder email is sent to pathology department coordinator, 
pathologist, radiation oncologist and surgeon. 
• 
When pathology report is out, surgeon and radiation oncology are automatically emailed to 
notify of new result.  
• 
Target date for dental extraction set to 14 days after post-operative pathology report. 
 
For low-risk patients (normal track): 
• 
Pre-operative radiation oncology consult done at same time as otolaryngology consult. 
• 
Target date for post-operative pathology report set to 28 days. 
o On day of surgery, a reminder email is sent to pathology department coordinator, 
pathologist, radiation oncologist and surgeon. 
o 5 days before target, a reminder email is sent to pathology department coordinator, 
pathologist, radiation oncologist and surgeon. 
• 
When pathology report is out, surgeon and radiation oncology are automatically emailed to 
notify of new result.  
• 
Target date for dental extraction set to 7 days after post-operative pathology report. 
 
4.3.3. Outcome variable 
• 
Surgery to post-operative radiation therapy (SPORT - defined as number of days from surgery to 
initiation of radiation therapy or chemoradiation) ≤42 days. 
• 
Overall survival, with events defined as death from any cause. 
• 
Locoregional survival, with events defined as locoregional recurrence (primary site or cervical 
node) or death. 
• 
Distant metastasis-free survival, with events defined as distant metastasis or death.  

 
 
 
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• 
Recurrence-Free Survival, with events defined as any recurrence (local, regional, or distant). 
Deaths without recurrence are censored. 
• 
Disease-free survival, with events defined as recurrence (any site) or death. 
All oncologic outcomes are defined from date to surgery to date of event.  
 
4.3.4. Clinical and demographic variablesPatient demographics 
o Age  
o Sex  
o Smoking status (current, previous, never) 
o Number of pack-years 
o Marijuana status (current, previous, never) 
o Alcohol status (current, previous, never) 
o Number of alcohol consumptions per week 
• 
Prior medical conditions and active comorbidities  
o Prior head & neck malignancy (yes/no) 
o Prior non-head & neck malignancy (yes/no) 
o Prior head & neck radiation (yes/no) 
§ 
If yes, dose (in Gray) 
o Charlson-Deyo Comorbidity index  
o ECOG score 
 
4.3.5. CovariatesPre-operative tumour characteristics 
o Tumour size on CT scan 
o Tumour site (oral cavity vs larynx) 
o Tumour subsite 
§ 
Oral cavity: lip, alveolar ridge (maxillary or mandibular), hard palate, oral 
tongue, floor of the mouth, retromolar trigone, buccal mucosa 
o Clinical T status 
o Clinical N status  
o Clinical M status 
• 
Surgical and post-operative characteristics  
o Surgery duration (in minutes) 
o Surgical complication (yes/no) 
o Tracheostomy (yes/no) 
o Free flap (yes/no) 
o Local flap (yes/no) 
o Neck dissection (yes/no) 
o Post-operative hospital length of stay (in days) 
• 
Pathological tumour characteristics 
o Tumour size  
o pT status 
o pN status  
o number of positive nodes 
o margin status 
o margin (in mm) 
o extranodal extension  
o perineural invasion 
 

 
 
 
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4.3.6. Study conduct and specific strategies for minimizing biasesSome may argue that there are 
seasonal differences in treatment delays (ie. some periods during the year are more susceptible 
to causing in health care administration delays – for example, during holiday periods). In order 
to minimize this bias, we will run both control and intervention group for 12 months and 12 
months, respectively. 
4.4. Statistical aspectsSample size 
The estimated sample size was calculated for our study. Employing a two-sided alpha of 0.05 and a 
beta of 0.20, we aim to investigate the impact of an intervention on the risk of prolonged S-PORT 
(>42 days). Based on prior Canadian literature, approximately 80% of patients have prolonged S-
PORT 3,19,20. Our hypothesis posits that with the intervention, the risk of prolonged S-PORT will 
decrease substantially to at least 50 percent. Based on sample size calculations, it has been 
determined that a cohort of 38 patients in each group will be necessary to detect statistically 
significant differences. 
4.4.2. Statistical analysis 
Statistical analysis will be performed using R statistical software. The aim of this pilot study of a new 
coordination intervention is to determine if the implementation of this intervention will result in higher 
adherence to recommended treatment delays (S-PORT ≤42 days). Descriptive characteristics will be 
presented as mean (standard deviation) or median (interquartile range) for continuous parameters and 
frequency distributions (number and proportion) for categorical parameters for all patient 
demographics and baseline characteristics. Univariate logistic regression will be used identify covariates 
associated with prolonged treatment time intervals. Multivariate logistic regression will be used to 
explore the independent association between this intervention and treatment time intervals. We will 
use a combination of the univariate logistic regression (with variables showing a noteworthy statistical 
association as indicated by a P < 0.10), expert opinions and variables that have been shown to be 
associated with treatment delays in the previously published literature to select covariates that are 
entered in the multivariate model. An alpha level of P < 0.05 was used as the cut-off for statistical 
significance in the multivariable analysis.  
5. Surveillance and safetyNot applicable. 
6. Ethical considerationsThis study will comply with all applicable laws, regulations, and 
guidance regarding patient protection including patient privacy. As this study aims to evaluate the 
implementation of an administrative intervention that aims to improve care coordination between 
healthcare providers but does not directly reach patients, the study presents no risk to the patients. 
It is therefore proposed that the need for consent be waived. Participant information will be 
deidentified. Data will be collected and stored using REDCAP. A backup of the data will be stored on 
a USB key, kept in a secure locked room, until the project is completed. Only identified members of 
the research team will have access to the database for data management and conduction of the 
analyses. The data will be destroyed once the project is completed and the data has been analyzed 
(<7 years). 
 
It is the intent of the collaborators to publish the study results. Results will be sent out to and 
disseminated at scientific meetings. Further, a manuscript will be prepared and if possible, published in 
a renowned scientific journal. No patient will be identifiable in the presentations or publications.  All 
authors should meet the criteria for authorship, and all people who meet the criteria should be authors. 
Potential conflicts of interest should be disclosed.  Each author should have participated sufficiently in 
the work to take public responsibility for appropriate portions of the content. 

 
 
 
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8. Annexes 

 
 
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