Oral cavity cancer is a major
public health problem. Adequate margin of resection determine the oncological
outcome. Paraffin fixed assessment is gold standard but its results will be
available only after surgery. There is need of reliable method of intraoperative
margin assessment. Intraoperative margin assessment is still an active area of
research. Gross assessment by surgeon and frozen section analysis by
pathologist are commonly used methods. There is lack of head to head comparison
between these two methods.We proposed to conduct a randomized controlled trial
comparing these two methods to determine the oncological outcomes and their
performance characteristics.
Research Question
Is gross examination of specimen
equally effective as frozen section analysis for the assessment of margins in
oral cavity cancers?
Research Hypothesis
We believe that gross examination
of the oral cavity cancer specimen is not inferior to frozen section
examination for the assessment of intraoperative margin in terms of performance
and oncological safety.
Aim and Objectives
To study the difference between
gross and frozen section for intraoperative margin assessment for oral cavity
cancers in terms of the performance and early oncological outcome.
Primary objective
·
To
study the local recurrence free survival with the methods of intraoperative
margin assessment for oral cavity cancers within 6 months.
Secondary Objective
·
To
study the performance characteristics (Sensitivity, Specificity, NPV, PPV, and
Accuracy) of gross examination and frozen section methods of intraoperative
margin assessment for oral cavity cancers.
·
To
study the concordance of margin assessment between the two methods intraoperatively.
·
To
assess the cost feasibility and time duration between the 2 group of patients.
STUDY METHODOLOGY
Study Design
It is single center, phase 2
Non-inferiority, single blinded Randomized Controlled Trial with
allocation ratio of 1:1.
Study participants
All consecutive patients
undergoing surgery for oral cavity cancer within the study period without
any exclusion criteria features
will be considered for the study. After consent they will be randomized to
gross section arm and frozen section arm. The gross section and frozen section
arms 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 resection
upfront,
Adequate Organ function to
tolerate complete treatment.
Exclusion Criteria
Not giving consent, Salvage
surgery, recurrent cancer, Non-squamous cell carcinoma histology.
Blinding :
The assigned investigator for the
study would be blinded who would be called intraoperatively
After the specimen resection to
decide 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 frozen
section assessment. The investigator would be blinded.
Randomization details :
Patients will be randomized using
closed envelop technique into two groups: Group 1 which will include patients
who 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 the
resection. The surgeon will call the trial coordinator assigned for the study
know the randomization arm.
Sample Size :
Based on the retrospective cohort
study by Manish Mair et. al. and Maharaj et. al., e the local recurrence- free
survival 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 came
out to be 62 in each arm. Taking 10% incomplete data and attrition, the final
sample size in each arm would be 71.
Methodology :
The patients undergoing surgery
for whom the group would be intra operatively by sealed Envelop Gross
examination would be cleaned and margins measured grossly with measuring tape.
If the margins are inadequate < 7 mm it will undergo revision Frozen section
for which samples would be sent to the pathologist all the margins ( 5 )
anterior posterior medial and lateral with deep margins would be assessed and
the information regarding margin inadequacy would be conveyed to the surgeon if
any margin is < 5 mm.
Study feasibility:
Based on our experience with oral
cancer patient load meeting the eligibility criteria, we presumed to accrue
15-20 cases in a month. We are expecting to complete our patient accrual in one
year. The minimal sixth month of follow-up would be possible during the study
period.
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