Ignite Creation Date:
2024-06-16 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06438939
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-03
First Post:
2024-05-20
Brief Title:
NBI for Early Diagnosis of OPMDOSCC
Sponsor:
Cardarelli Hospital
Organization:
Cardarelli Hospital
Study Overview
Official Title:
Narrow Band Imaging NBI for Early Diagnosis of Oral Squamous Cell Carcinoma OSCC and Oral Potentially Malignant Disorders OPMD
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
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:
NBI_Oral
Brief Summary:
Early detection - possibly at its pre-malignant stages Oral Potentially Malignant Disorders OPMD - with periodic surveillance is thus fundamental for limiting disease burden hopefully reducing the incidence of advanced stages OSCC and increasing survival Narrow Band Imaging NBI has proved itself as promising tool for helping clinician both for diagnosis and therapy Yet there is no definitive scientific evidence that NBI is superior to common oral examination with white light WLOE for diagnosing OSCCOPMD We thus propose a randomised clinical trial understand its role in this field
Detailed Description:
Introduction Oral squamous cell carcinoma OSCC is a malignant condition arising from the mucosal lining of the mouth It is the most frequent malignancy that affects the oral cavity with more than 350000 new incident cases estimated worldwide yearly causing over 150000 deaths in 2020
The 5-year overall survival rate of OSCC - around 60- has not significantly improved during the last decades despite general clinical and therapeutic advances Considering that patients with initial stages I-II of OSCC show survival rates of 80-90 while advanced-stages III-IV survival stands lower than 50 it is apparent that the overall survival low value reflects that most cases are diagnosed at advanced stages Early detection - possibly at its pre-malignant stages Oral Potentially Malignant Disorders OPMD - with periodic surveillance is thus fundamental for limiting disease burden hopefully reducing the incidence of advanced stages OSCC and increasing survival
Narrow Band Imaging NBI is a non-invasive imaging fiberoptic technique which allows the analysis of the thin sub-epithelial vascularisation through visual magnification There is high scientific evidence that NBI fibroscopy facilitate early diagnosis of squamous cancers of the upper aerodigestive tract In the oral cavity it has proved itself as promising tool for helping clinician both for diagnosis and therapy
Yet there is no definitive scientific evidence that NBI is superior to common oral examination with white light WLOE for diagnosing OSCCOPMD
Materials Methods The primary outcome of this study is a comparison of the detection rates of OSCC or an OPMD using oral examination with white light WLOE and Narrow Band Imaging NBI
The secondary outcome is to estimate the overall diagnostic accuracy sensitivity specificity NPV PPV of the two methods according to the presenting condition
patients with any oral mucosal lesions necessitating an initial diagnosis
patients with known OPMDs or had their OPMDs excised
patients with history of Head Neck HNSCC
high risk patients heavy smokers drinkers individuals with Fanconi anaemia dyskeratosis congenita xeroderma pigmentosum Li-Fraumeni syndrome Bloom syndrome ataxia-telangiectasia and Cowden syndrome with no oral lesiondisease at the time of examination
To evaluate diagnostic accuracy we propose to use the histologic diagnosis from a biopsy specimen as the gold standard diagnosis
Study Design This clinical trial once approved by Ethical Committee will be registered on ClinicalTrialgov online platform Patients will be randomly assigned to receive primary WLOE or primary NBI To improve the quality of the reporting in the diagnostic accuracy study we complied with the Standards for Reporting of Diagnostic Accuracy STARD initiative We set WLOE as reference standard and NBI as index test Random assignment will be performed for each case by an investigator using National Insitute of Health NIH - National Cancer Institute Clinical Trial Randomization Tool httpsctrandomizationcancergovtool This Web site is available only to the study participants Using a minimization algorithm the selection of the primary examination is balanced with respect to five stratification variables institution age sex alcohol consumption and smoking habit In order to give patients the highest possible standard of care we will perform both imaging methods in a back-to-back fashion so that primary WLOE is followed by NBI and primary NBI is followed by WLOE To avoid any bias the report of the first examination is completed before the second imaging is started
Study population and study design are summarised in the flowchart Study Populations
The protocol and consent form for this study has been approved by the Ethical committee of the AORN ANTONIO CARDARELLI Hospital n0624 Naples Italy written informed consent is obtained from all patients The inclusion criteria are
Patients with soft tissue mucosal lesions of the oral cavity who arrive for an initial first diagnosis group 1
Patients with history OPMD clinically evident lesions group 2a lesions excised group 2b who are in follow-up OPMDs included are eg Leukoplakia erythroleukoplakia erythroplakia oral lichen planus oral lichenoid lesion
Patients with history of HNSCC OSCC group 3a sinonasal nasopharynx oropharynx larynx oesophagus group 3b
High risk see above individuals with no known oral mucosal disease group 4
Exclusion criteria will be
patients who did not need a biopsy nor after WLOE eg normal mucosa anatomical variation nor after NBI pattern I
patients who despite indication were not suitable to undergo biopsy given his her systemic conditions The pathologists will be blinded to the endoscopic information In case biopsy showed OSCC patients would be directed for subsequent diagnostictherapeutic pathway OPMD cases will be managed in the unit under routine care
Calculation of the Sample Size For the purposes of this study we set the probability for error alfa to 05 with a power of 080 reflecting a beta error of 2 We estimated that the NBI system would increase the detection yield for superficial cancer by at least threefold compared with conventional WLOE This resulted in a calculated sample size of 125 patients per category WLOENBI rounded up in 60 30 WLOE 30 NBI patients per group 1234
Endoscopic Examination All NBI observations will include the whole oral cavity including mucosal aspect of lips NBI system consist in a flexible fiberscope producing magnified images to a fullHD monitor Angle of the fiberscope emitting light WL NBI and recording is controlled throug a joystick at fiberscopes grip
NBI imaging for Intrapapillary capillary loops IPCL patterns of each lesion will be determined according to modifications made by Farah of the system proposed by Takano as it proved to be the most effective system for oral lesions
type 0 IPCL not detectable
type I physiological arborisation of IPCL
type II meandering or dilated IPCL
type III convolutedwinding andor elongated IPCL
type IV complete loss of organisationannihilation of IPCL The biopsy sample will be taken from the area of highest NBI pattern detected during NBI examination
To maintain the quality of the NBI inspection and to reduce risk of operator-dependent bias before the study is started all the participating operators will be trained by an expert Each NBI fibroscopy is recorded and reviewed by an expert AG blinded to the result of an eventual biopsy and to the other evaluation result Expert review is then sent back to the initial operator Differences in determination of IPCL pattern will be resolved through discussion obtaining a consensus pattern In case the consensus pattern showed necessity for biopsy pattern III IV if not already performed the patient is re-called to undergo biopsy
Pathologic Evaluation Biopsy specimens are taken from each lesion after the completion of both types of imaging and then reviewed by an experienced pathologist according to the WHO Blue book 2024 classification
Statistical Analysis The absolute and relative frequencies for qualitative variables were calculated for each group Statistical analysis was performed using SPSS version 17 software SPSS Chicago IL The continuous variables are expressed as medians and ranges Continuous data were compared using the MannWhitney U test Pearsons 2 test or Fishers exact test was used to analyze categoric data to compare proportions All P values were two-tailed and a P value of 05 was considered significant Concordance between operators NBI pattern was evaluated with Fleiss fixed-marginal Kappa test with Gwets variance formula 95 CI considering values 0 as indicating no agreement 001-020 as none to slight 021-040 as fair 041-060 as moderate 061-080 as substantial and 081-100 as almost perfect agreement
The 5-year overall survival rate of OSCC - around 60- has not significantly improved during the last decades despite general clinical and therapeutic advances Considering that patients with initial stages I-II of OSCC show survival rates of 80-90 while advanced-stages III-IV survival stands lower than 50 it is apparent that the overall survival low value reflects that most cases are diagnosed at advanced stages Early detection - possibly at its pre-malignant stages Oral Potentially Malignant Disorders OPMD - with periodic surveillance is thus fundamental for limiting disease burden hopefully reducing the incidence of advanced stages OSCC and increasing survival
Narrow Band Imaging NBI is a non-invasive imaging fiberoptic technique which allows the analysis of the thin sub-epithelial vascularisation through visual magnification There is high scientific evidence that NBI fibroscopy facilitate early diagnosis of squamous cancers of the upper aerodigestive tract In the oral cavity it has proved itself as promising tool for helping clinician both for diagnosis and therapy
Yet there is no definitive scientific evidence that NBI is superior to common oral examination with white light WLOE for diagnosing OSCCOPMD
Materials Methods The primary outcome of this study is a comparison of the detection rates of OSCC or an OPMD using oral examination with white light WLOE and Narrow Band Imaging NBI
The secondary outcome is to estimate the overall diagnostic accuracy sensitivity specificity NPV PPV of the two methods according to the presenting condition
patients with any oral mucosal lesions necessitating an initial diagnosis
patients with known OPMDs or had their OPMDs excised
patients with history of Head Neck HNSCC
high risk patients heavy smokers drinkers individuals with Fanconi anaemia dyskeratosis congenita xeroderma pigmentosum Li-Fraumeni syndrome Bloom syndrome ataxia-telangiectasia and Cowden syndrome with no oral lesiondisease at the time of examination
To evaluate diagnostic accuracy we propose to use the histologic diagnosis from a biopsy specimen as the gold standard diagnosis
Study Design This clinical trial once approved by Ethical Committee will be registered on ClinicalTrialgov online platform Patients will be randomly assigned to receive primary WLOE or primary NBI To improve the quality of the reporting in the diagnostic accuracy study we complied with the Standards for Reporting of Diagnostic Accuracy STARD initiative We set WLOE as reference standard and NBI as index test Random assignment will be performed for each case by an investigator using National Insitute of Health NIH - National Cancer Institute Clinical Trial Randomization Tool httpsctrandomizationcancergovtool This Web site is available only to the study participants Using a minimization algorithm the selection of the primary examination is balanced with respect to five stratification variables institution age sex alcohol consumption and smoking habit In order to give patients the highest possible standard of care we will perform both imaging methods in a back-to-back fashion so that primary WLOE is followed by NBI and primary NBI is followed by WLOE To avoid any bias the report of the first examination is completed before the second imaging is started
Study population and study design are summarised in the flowchart Study Populations
The protocol and consent form for this study has been approved by the Ethical committee of the AORN ANTONIO CARDARELLI Hospital n0624 Naples Italy written informed consent is obtained from all patients The inclusion criteria are
Patients with soft tissue mucosal lesions of the oral cavity who arrive for an initial first diagnosis group 1
Patients with history OPMD clinically evident lesions group 2a lesions excised group 2b who are in follow-up OPMDs included are eg Leukoplakia erythroleukoplakia erythroplakia oral lichen planus oral lichenoid lesion
Patients with history of HNSCC OSCC group 3a sinonasal nasopharynx oropharynx larynx oesophagus group 3b
High risk see above individuals with no known oral mucosal disease group 4
Exclusion criteria will be
patients who did not need a biopsy nor after WLOE eg normal mucosa anatomical variation nor after NBI pattern I
patients who despite indication were not suitable to undergo biopsy given his her systemic conditions The pathologists will be blinded to the endoscopic information In case biopsy showed OSCC patients would be directed for subsequent diagnostictherapeutic pathway OPMD cases will be managed in the unit under routine care
Calculation of the Sample Size For the purposes of this study we set the probability for error alfa to 05 with a power of 080 reflecting a beta error of 2 We estimated that the NBI system would increase the detection yield for superficial cancer by at least threefold compared with conventional WLOE This resulted in a calculated sample size of 125 patients per category WLOENBI rounded up in 60 30 WLOE 30 NBI patients per group 1234
Endoscopic Examination All NBI observations will include the whole oral cavity including mucosal aspect of lips NBI system consist in a flexible fiberscope producing magnified images to a fullHD monitor Angle of the fiberscope emitting light WL NBI and recording is controlled throug a joystick at fiberscopes grip
NBI imaging for Intrapapillary capillary loops IPCL patterns of each lesion will be determined according to modifications made by Farah of the system proposed by Takano as it proved to be the most effective system for oral lesions
type 0 IPCL not detectable
type I physiological arborisation of IPCL
type II meandering or dilated IPCL
type III convolutedwinding andor elongated IPCL
type IV complete loss of organisationannihilation of IPCL The biopsy sample will be taken from the area of highest NBI pattern detected during NBI examination
To maintain the quality of the NBI inspection and to reduce risk of operator-dependent bias before the study is started all the participating operators will be trained by an expert Each NBI fibroscopy is recorded and reviewed by an expert AG blinded to the result of an eventual biopsy and to the other evaluation result Expert review is then sent back to the initial operator Differences in determination of IPCL pattern will be resolved through discussion obtaining a consensus pattern In case the consensus pattern showed necessity for biopsy pattern III IV if not already performed the patient is re-called to undergo biopsy
Pathologic Evaluation Biopsy specimens are taken from each lesion after the completion of both types of imaging and then reviewed by an experienced pathologist according to the WHO Blue book 2024 classification
Statistical Analysis The absolute and relative frequencies for qualitative variables were calculated for each group Statistical analysis was performed using SPSS version 17 software SPSS Chicago IL The continuous variables are expressed as medians and ranges Continuous data were compared using the MannWhitney U test Pearsons 2 test or Fishers exact test was used to analyze categoric data to compare proportions All P values were two-tailed and a P value of 05 was considered significant Concordance between operators NBI pattern was evaluated with Fleiss fixed-marginal Kappa test with Gwets variance formula 95 CI considering values 0 as indicating no agreement 001-020 as none to slight 021-040 as fair 041-060 as moderate 061-080 as substantial and 081-100 as almost perfect agreement
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None