Performance & Early Oncological Outcomes of Intraoperative Gross Examination and Frozen Section for Oral Cavity Squamous Cell Cancer: A Phase 2 Non-Inferiority Single-Blinded Randomized Controlled Trial

Oral cavity cancer is a majorpublic health problem. Adequate margin of resection determine the oncologicaloutcome. Paraffin fixed assessment is gold standard but its results will beavailable only after surgery. There is need of reliable method of intraoperativemargin assessment. Intraoperative margin assessment is still an active area ofresearch. Gross assessment by surgeon and frozen section analysis bypathologist are commonly used methods. There is lack of head to head comparisonbetween these two methods.We proposed to conduct a randomized controlled trialcomparing these two methods to determine the oncological outcomes and theirperformance characteristics.

Research Question

Is gross examination of specimenequally effective as frozen section analysis for the assessment of margins inoral cavity cancers?

Research Hypothesis

We believe that gross examinationof the oral cavity cancer specimen is not inferior to frozen sectionexamination for the assessment of intraoperative margin in terms of performanceand oncological safety.

Aim and Objectives

To study the difference betweengross and frozen section for intraoperative margin assessment for oral cavitycancers in terms of the performance and early oncological outcome.

Primary objective

·        Tostudy the local recurrence free survival with the methods of intraoperativemargin assessment for oral cavity cancers within 6 months.

Secondary Objective

·        Tostudy the performance characteristics (Sensitivity, Specificity, NPV, PPV, andAccuracy) of gross examination and frozen section methods of intraoperativemargin assessment for oral cavity cancers.

·        Tostudy the concordance of margin assessment between the two methods intraoperatively.

·        Toassess the cost feasibility and time duration between the 2 group of patients.

STUDY METHODOLOGY

Study Design

It is single center, phase 2Non-inferiority, single blinded Randomized Controlled Trial with

allocation ratio of 1:1.

Study participants

All consecutive patientsundergoing surgery for oral cavity cancer within the study period without

any exclusion criteria featureswill be considered for the study. After consent they will be randomized togross section arm and frozen section arm. The gross section and frozen sectionarms will be compared in terms of about the margins of the specimen removed,TNM staging , need for Adjuvant treatment.

 Inclusion Criteria

Age 18 year or old,

ECOG PS: 0-2,

HPE proven Oral Cavity SCC,Treatment-Naïve,

Undergoing curative resectionupfront,

Adequate Organ function totolerate complete treatment.

Exclusion Criteria

Not giving consent, Salvagesurgery, recurrent cancer, Non-squamous cell carcinoma histology.

Blinding :

The assigned investigator for thestudy would be blinded who would be called intraoperatively

After the specimen resection todecide the methods of margin assessment. As the surgeon or

Pathologist cannot be blinded,he/she is involved in resection and measure as well as need to contact the

pathologists for the frozensection assessment. The investigator would be blinded.

Randomization details :

Patients will be randomized usingclosed envelop technique into two groups: Group 1 which will include patientswho will have gross margin assessment, and Group 2 frozen section for margin assessment.Randomization of patients will be done at the time of surgery, after theresection. The surgeon will call the trial coordinator assigned for the studyknow the randomization arm.

Sample Size :

Based on the retrospective cohortstudy by Manish Mair et. al. and Maharaj et. al., e the local recurrence- freesurvival is between 65-75%. We took the non-inferiority margin limit of 10%with 90% power and a significance level of 0.05, the required sample size cameout to be 62 in each arm. Taking 10% incomplete data and attrition, the finalsample size in each arm would be 71.

Methodology :

The patients undergoing surgeryfor whom the group would be intra operatively by sealed Envelop Grossexamination would be cleaned and margins measured grossly with measuring tape.If the margins are inadequate < 7 mm it will undergo revision Frozen sectionfor which samples would be sent to the pathologist all the margins ( 5 )anterior posterior medial and lateral with deep margins would be assessed andthe information regarding margin inadequacy would be conveyed to the surgeon ifany margin is < 5 mm.

Study feasibility:

Based on our experience with oralcancer patient load meeting the eligibility criteria, we presumed to accrue15-20 cases in a month. We are expecting to complete our patient accrual in oneyear. The minimal sixth month of follow-up would be possible during the studyperiod.