Gross Examinations Versus Frozen Section for Assessment of Surgical Margins in Oral Cancers

Study Overview
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Brief Summary
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Surgical margin is a significant prognostic factor in oral cavity squamous cell carcinoma (OCSCC)[1,2,3]. Intra-operative frozen section (FS) has been routinely used by the surgeons to achieve adequate surgical margins. However published literature has failed to show a conclusive benefit of FS in improving oncological outcomes(4-7). The overall identification rate of the inadequate margins by FS is variable with figures in the literature ranging from25-34%.(8-10) Revision of margins based on FS is widely practiced in centers where facility for FS is available. However this has not shown to significantly improve local control when compared to cases in which FS was not utilized , in a comparative study done at Tata memorial Hospital(TMH) (5) More-over FS is a costly procedure, and sparsely available in resource- poor countries. In a recently conducted retrospective study of 1237 patients conducted at TMH, the cost benefit ratio of FS for assessment of margin is as low as 12:1(11). In another prospective study performed at the same center , investigators found that gross examination (GE) of margins by the surgeons was as effective as FS, and achievement of gross 7mm margin all around the tumor obviated the need for FS (12). In a recent meta-analysis of 8 studies that looked at the utility of frozen section and had uniformity in frozen section analysis and definition of close margins, they concluded that revision of margins based on FS does not improve oncological outcomes and further prospective studies are needed to explore this contentious issue (13). With this background, a prospective RCT is planned to explore if gross examination by surgeon and subsequent revision of margin (if necessary) is an equally effective alternative to Frozen section based revision in a randomized controlled trial.

Official Title
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Intra-operative Gross Examination Versus Frozen Section for Achievement of Adequate Margin in Patients Undergoing Surgery for Oral Cavity Squamous Cell Carcinoma: A Randomized Controlled Trial

Conditions
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Oral Cavity Cancer

Intervention / Treatment
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* Procedure: Gross examination of the resection specimen
* Procedure: Frozen section


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven treatment naïve cases of OCSCC who are planned for curative surgery with en-bloc removal of the tumor with adequate margin In detail assessment of the primary tumor is possible pre-operatively Written informed consent Age more than 18 years Exclusion Criteria: Multifocal disease Clinically evident field cancerization Previous treatment for oral cavity cancer - Surgery /chemo or radiotherapy -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gross examination<br>measurement of the surgical margins will be done by the surgeon in the operating room using sterile scale after resection of the primary tumor . | Procedure: Gross examination of the resection specimen<br>* measurement of the surgical margin by the operating surgeon using sterile scale, margins <7mm will be revised on table<br>|
| Active Comparator: Frozen section<br>frozen section examination of surgical margins will be done by the pathologist. | Procedure: Frozen section<br>* frozen section evaluation of the specimen by the pathologist<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| local recurrence free survival (LRFS) between two arms | To determine the difference between the local recurrence free survival (LRFS) between intra operative gross examination by the surgeon compared with microscopic examination using frozen sections by the pathologist for the assessment of surgical margin in patients undergoing surgery for OCSCC. Local recurrence will be defined as - tumor recurrence at the same subsite or or at margins of previous surgery &/ reconstruction with or without nodal recurrence /distant metastases withing two years after completion of the treatment. - Isolated regional &/or distant metastasis without recurrence at local site will be recorded however it will not be considered as the event for measuring LRFS | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of gross examination | To determine the accuracy of intra operative gross examination by the surgeon compared with microscopic examination of frozen sections by the pathologist for the assessment of surgical margin as compared to the final histopathology report as the gold standard. | 5 years | 
| Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of GE and FS for the assessment of surgical margin |  | 5years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral squamous Cell carcinoma, frozen section, local recurrence