Ignite Creation Date:
2024-05-06 @ 8:26 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06387004
Status:
RECRUITING
Last Update Posted:
2024-04-26
First Post:
2024-03-01
Brief Title:
Radiation-Related Dysphagia Development Prediction Using a Two-Step Ultrasonographic Model R-2D-2
Sponsor:
Hopital Forcilles
Organization:
Hopital Forcilles
Study Overview
Official Title:
Evaluation of the Prognostic Value of Aerodigestive Tract Ultrasound in the Occurrence of Radiotherapy-related Swallowing Disorders in Head and Neck Cancer Patients
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
R-2D-2
Brief Summary:
Radiotherapy for head and neck cancers HNC heightens the risk of swallowing disorders SD impacting nutrition quality of life and overall health leading to increased hospitalization and mortality Dietary plans hinge on patients nutritional status swallowing ability and prognosis Early interventions are crucial emphasizing the need for precise assessments guiding prognosis specifying structures for intervention and facilitating targeted rehabilitation
Clinical examinations lack precision while existing complementary methods like videofluoroscopy or Fiberoptic Endoscopic Evaluation of Swallowing are invasive irradiating resource-intensive and challenging to access with uncertain prognostic values
Ultrasound imaging emerges as a non-invasive alternative offering morphological and dynamic evaluation of swallowing-related structures It enables qualitative and quantitative analyses improving precision in targeting structures for rehabilitation Researchers propose an ultrasound predictive model to anticipate SD risk during HNC radiotherapy assessing its reliability and accuracy
Over eighteen months 124 outpatients beginning HNC radiotherapy at Forcilless Hospital will undergo weekly clinical and water-swallow tests by a speech language therapist with videofluoroscopy when SD is suspected Ultrasound evaluations pre-treatment and at seven and fourteen days will be conducted by blinded ultrasonographers Cox models will test ultrasound measurement thresholds for SD prediction estimating sensitivity specificity and prediction values A global ultrasound predictive model will be developed via logistic multivariable regression
The study aims to establish an association between ultrasound markers and SD improving early detection for tailored management This non-invasive alternative to videofluoroscopy offers potential for enhancing patient outcomes in HNC radiotherapy
Clinical examinations lack precision while existing complementary methods like videofluoroscopy or Fiberoptic Endoscopic Evaluation of Swallowing are invasive irradiating resource-intensive and challenging to access with uncertain prognostic values
Ultrasound imaging emerges as a non-invasive alternative offering morphological and dynamic evaluation of swallowing-related structures It enables qualitative and quantitative analyses improving precision in targeting structures for rehabilitation Researchers propose an ultrasound predictive model to anticipate SD risk during HNC radiotherapy assessing its reliability and accuracy
Over eighteen months 124 outpatients beginning HNC radiotherapy at Forcilless Hospital will undergo weekly clinical and water-swallow tests by a speech language therapist with videofluoroscopy when SD is suspected Ultrasound evaluations pre-treatment and at seven and fourteen days will be conducted by blinded ultrasonographers Cox models will test ultrasound measurement thresholds for SD prediction estimating sensitivity specificity and prediction values A global ultrasound predictive model will be developed via logistic multivariable regression
The study aims to establish an association between ultrasound markers and SD improving early detection for tailored management This non-invasive alternative to videofluoroscopy offers potential for enhancing patient outcomes in HNC radiotherapy
Detailed Description:
Radiotherapy for head and neck cancers increases the risk of Swallowing Disorders SD which can have serious consequences for nutrition quality of life and overall health
Early intervention strategies could greatly benefit highlighting the importance of assessments offering insights into patients prognosis identifying which specific structures require intervention and enabling a targeted rehabilitation approach
However the clinical examination lacks precision Complementary examinations such as videofluoroscopy or Fiberoptic Endoscopic Evaluation of Swallowing FEES are irradiating or invasive consume numerous resources and are difficult to access Whats more their prognostic values are not known
In this context ultrasound imaging has garnered increased interest for assessing swallowing disorders Recognised for its non-invasive nature and its ability to overcome conventional constraints ultrasound holds promise in integrating morphological and dynamically swallowing-related structures evaluation This approach enabling both qualitative and quantitative analysis of multiple structures would enhance the precision in targeting structures for rehabilitation
The researchers intend to create an ultrasound predictive model to anticipate the risk of developing swallowing disorders during head and neck cancer radiotherapy
Hypothesis The investigators hypothesize that one or more ultrasound variables are independently associated with swallowing disorder development and worsening nutritional status during radiotherapy treatment for head and neck cancer
Objectives Main objective The main objective of this study is to evaluate the predictive capacity of different ultrasound markers of the VADS on the incidence of TD during radiotherapy treatment for CTC
Secondary objectives
In a population of patients treated with radiotherapy for CTC
Assessing the reliability of ultrasound measurements
Evaluate the feasibility of ultrasound measurements
To evaluate the predictive ability of the change in ultrasound markers after 1 and 2 weeks of radiotherapy on the incidence of TD
To determine whether ultrasound markers associated with the onset of TD improve a predictive model including known predictors
Assessing the association between ultrasound markers and the incidence of undernutrition
To evaluate the predictive ability of the change in ultrasound markers after 1 and 2 weeks of radiotherapy on the incidence of undernutrition
Evaluate the association between ultrasound markers and quality of life in relation to TD
Study design
Prospective observational single-centre study will be performed per the ethical standards of the Declaration of Helsinki and will be reported following the standards for the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis guidelines TRIPOD
Population
One hundred and twenty-four outpatients starting a radiotherapy treatment for head and neck cancer will be enrolled at Radiotherapy Services at Forcilless Hospital during a eighteen-months period All consecutive patients will be screened at admission and will be included if they satisfy the eligibility criteria All patients will provide oral consent to participate by the clinical research French laws The patients participation will be equivalent to the duration of their radiotherapy treatment The maximum additional time needed for research interventions is 40 minutes
Data collection Data will be recorded using an online case report form Datacapt Demographic data comorbidities medical and surgical history will be recorded at inclusion Clinical videoflyoroscopy and ultrasound measurements will also be recorded On-site monitoring is planned every month
The ultrasound examination will be conducted initially on the seventh and fourteenth days of radiotherapy always preceding other swallowing evaluations
Ultrasound examination
Ultrasonography will be performed using a Sonosite E2 Expert ultrasound device Digital Color Doppler Ultrasound System Sonoscape medical corp China with a 7-10 MHz linear and a 3-5 MHz probes Detailed information for ultrasound procedure is described in the research protocol Ultrasonography will be performed with the patients in near-to-supine position 30
To assess the value of variation in these examinations during radiotherapy as a predictive factor a total of three ultrasound examinations will be performed prior to the first radiotherapy treatment and after seven and fourteen days Ultrasonographers will be blinded from all patients status and previous examination
Ultrasound evaluation will focus on the movements or morphology of structures such as the tongue laryngeal movement or suprahyoid muscles
In order to assess inter-examiner reliability and only during the first ultrasound evaluation the tests will be carried out by two different operators on a consecutive sample of patients To limit the examination time for each patient the investigators will use another consecutive sample of patients for intra-examiner reliability For the patients making up the samples used for reliability assessment only 10 extra will be added
Clinical evaluation All patients will undergo a standardized weekly clinical assessment conducted by a speech language therapist This assessment will involve an analytical evaluation of various structures tongue movement and strength laryngeal movement etc and swallowing tests following the volume-viscosity swallow test
Videofluoroscopy
VFSS is a radiographic procedure offering a dynamic view of oral pharyngeal and upper esophageal function during swallowing The radiologist and speech-language therapist collaborate to realise these evaluations Barium-mixed food and fluid aid visibility via videofluoroscopy The examiner must evaluate the broadest range of the patients feeding options starting with the safest quantity and texture VFSS assesses swallow characteristics bolus movement patterns initiation nasopharyngeal reflux pharyngeal clearance laryngeal penetration and aspiration At any time examiners may halt the evaluation if deemed harmful with reasons recorded In instances of penetration or aspiration the speech-language therapist employs the Penetration-Aspiration Scale
Statistical plan
The study aims to assess the prognostic value of swallowing ultrasound in predicting the occurrence of swallowing disorders TDs during radiotherapy for CTC treatment The event under consideration is the development of TDs between patient inclusion and the completion of radiotherapy The analysis involves investigating the relationship between variables and TD occurrence Quantitative variables in multivariate models will be studied using restricted cubic splines and fractional polynomial methods for accurate assessment
Variable selection for the TD predictive model includes testing the prognostic values of ultrasound variables and adjustment variables through univariate Cox models Significant variables p 010 or those with known prognostic impact will be included in a multivariate Cox model Model calibration discrimination and internal validation will be evaluated using the c-index graphical calibration at 30 days and the bootstrap method
The estimation of TD onset times will utilize the Kaplan-Meier method comparing survival curves between groups defined by ultrasound variable thresholds with the log-rank test A prognostic score will be constructed from multivariate model results categorizing patients into low-risk intermediate-risk and high-risk groups Thresholds for categorization will be determined using Coxs method
Handling missing data involves either deleting observations with missing data or using data imputation methods depending on the origin and type of missing data Reproducibility assessment of ultrasound measurements includes inter-operator and intra-operator evaluations To assess inter-operator reproducibility measurements by two different operators will be compared while intra-operator reproducibility will be evaluated from measurements performed by the same operator 30 minutes apart A sample size of 40 patients is deemed necessary for reproducibility assessment based on Walter et als methodology
The tests will be performed at a significance level of 5 95 confidence intervals will be provided for each estimate
Calculations will be performed using SPSS v21 IBM and R software version 361 wwwR-projectorg
Sample size calculation
According to Harrells recommendations on the construction of multivariate models a maximum of 1 variable per 10 events should be included The investigators estimates the incidence of swallowing disorders in our patient population at 45 according to the literature The investigators aims to include a maximum of 5 variables in the multivariate model ie 112 patients required
Among the eligible patient population taking into account a 10 loss-of-sight rate it is necessary to include 124 patients
Early intervention strategies could greatly benefit highlighting the importance of assessments offering insights into patients prognosis identifying which specific structures require intervention and enabling a targeted rehabilitation approach
However the clinical examination lacks precision Complementary examinations such as videofluoroscopy or Fiberoptic Endoscopic Evaluation of Swallowing FEES are irradiating or invasive consume numerous resources and are difficult to access Whats more their prognostic values are not known
In this context ultrasound imaging has garnered increased interest for assessing swallowing disorders Recognised for its non-invasive nature and its ability to overcome conventional constraints ultrasound holds promise in integrating morphological and dynamically swallowing-related structures evaluation This approach enabling both qualitative and quantitative analysis of multiple structures would enhance the precision in targeting structures for rehabilitation
The researchers intend to create an ultrasound predictive model to anticipate the risk of developing swallowing disorders during head and neck cancer radiotherapy
Hypothesis The investigators hypothesize that one or more ultrasound variables are independently associated with swallowing disorder development and worsening nutritional status during radiotherapy treatment for head and neck cancer
Objectives Main objective The main objective of this study is to evaluate the predictive capacity of different ultrasound markers of the VADS on the incidence of TD during radiotherapy treatment for CTC
Secondary objectives
In a population of patients treated with radiotherapy for CTC
Assessing the reliability of ultrasound measurements
Evaluate the feasibility of ultrasound measurements
To evaluate the predictive ability of the change in ultrasound markers after 1 and 2 weeks of radiotherapy on the incidence of TD
To determine whether ultrasound markers associated with the onset of TD improve a predictive model including known predictors
Assessing the association between ultrasound markers and the incidence of undernutrition
To evaluate the predictive ability of the change in ultrasound markers after 1 and 2 weeks of radiotherapy on the incidence of undernutrition
Evaluate the association between ultrasound markers and quality of life in relation to TD
Study design
Prospective observational single-centre study will be performed per the ethical standards of the Declaration of Helsinki and will be reported following the standards for the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis guidelines TRIPOD
Population
One hundred and twenty-four outpatients starting a radiotherapy treatment for head and neck cancer will be enrolled at Radiotherapy Services at Forcilless Hospital during a eighteen-months period All consecutive patients will be screened at admission and will be included if they satisfy the eligibility criteria All patients will provide oral consent to participate by the clinical research French laws The patients participation will be equivalent to the duration of their radiotherapy treatment The maximum additional time needed for research interventions is 40 minutes
Data collection Data will be recorded using an online case report form Datacapt Demographic data comorbidities medical and surgical history will be recorded at inclusion Clinical videoflyoroscopy and ultrasound measurements will also be recorded On-site monitoring is planned every month
The ultrasound examination will be conducted initially on the seventh and fourteenth days of radiotherapy always preceding other swallowing evaluations
Ultrasound examination
Ultrasonography will be performed using a Sonosite E2 Expert ultrasound device Digital Color Doppler Ultrasound System Sonoscape medical corp China with a 7-10 MHz linear and a 3-5 MHz probes Detailed information for ultrasound procedure is described in the research protocol Ultrasonography will be performed with the patients in near-to-supine position 30
To assess the value of variation in these examinations during radiotherapy as a predictive factor a total of three ultrasound examinations will be performed prior to the first radiotherapy treatment and after seven and fourteen days Ultrasonographers will be blinded from all patients status and previous examination
Ultrasound evaluation will focus on the movements or morphology of structures such as the tongue laryngeal movement or suprahyoid muscles
In order to assess inter-examiner reliability and only during the first ultrasound evaluation the tests will be carried out by two different operators on a consecutive sample of patients To limit the examination time for each patient the investigators will use another consecutive sample of patients for intra-examiner reliability For the patients making up the samples used for reliability assessment only 10 extra will be added
Clinical evaluation All patients will undergo a standardized weekly clinical assessment conducted by a speech language therapist This assessment will involve an analytical evaluation of various structures tongue movement and strength laryngeal movement etc and swallowing tests following the volume-viscosity swallow test
Videofluoroscopy
VFSS is a radiographic procedure offering a dynamic view of oral pharyngeal and upper esophageal function during swallowing The radiologist and speech-language therapist collaborate to realise these evaluations Barium-mixed food and fluid aid visibility via videofluoroscopy The examiner must evaluate the broadest range of the patients feeding options starting with the safest quantity and texture VFSS assesses swallow characteristics bolus movement patterns initiation nasopharyngeal reflux pharyngeal clearance laryngeal penetration and aspiration At any time examiners may halt the evaluation if deemed harmful with reasons recorded In instances of penetration or aspiration the speech-language therapist employs the Penetration-Aspiration Scale
Statistical plan
The study aims to assess the prognostic value of swallowing ultrasound in predicting the occurrence of swallowing disorders TDs during radiotherapy for CTC treatment The event under consideration is the development of TDs between patient inclusion and the completion of radiotherapy The analysis involves investigating the relationship between variables and TD occurrence Quantitative variables in multivariate models will be studied using restricted cubic splines and fractional polynomial methods for accurate assessment
Variable selection for the TD predictive model includes testing the prognostic values of ultrasound variables and adjustment variables through univariate Cox models Significant variables p 010 or those with known prognostic impact will be included in a multivariate Cox model Model calibration discrimination and internal validation will be evaluated using the c-index graphical calibration at 30 days and the bootstrap method
The estimation of TD onset times will utilize the Kaplan-Meier method comparing survival curves between groups defined by ultrasound variable thresholds with the log-rank test A prognostic score will be constructed from multivariate model results categorizing patients into low-risk intermediate-risk and high-risk groups Thresholds for categorization will be determined using Coxs method
Handling missing data involves either deleting observations with missing data or using data imputation methods depending on the origin and type of missing data Reproducibility assessment of ultrasound measurements includes inter-operator and intra-operator evaluations To assess inter-operator reproducibility measurements by two different operators will be compared while intra-operator reproducibility will be evaluated from measurements performed by the same operator 30 minutes apart A sample size of 40 patients is deemed necessary for reproducibility assessment based on Walter et als methodology
The tests will be performed at a significance level of 5 95 confidence intervals will be provided for each estimate
Calculations will be performed using SPSS v21 IBM and R software version 361 wwwR-projectorg
Sample size calculation
According to Harrells recommendations on the construction of multivariate models a maximum of 1 variable per 10 events should be included The investigators estimates the incidence of swallowing disorders in our patient population at 45 according to the literature The investigators aims to include a maximum of 5 variables in the multivariate model ie 112 patients required
Among the eligible patient population taking into account a 10 loss-of-sight rate it is necessary to include 124 patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None