Gross Examinations Versus Frozen Section for Assessment of Surgical Margins in Oral Cancers
Primary Purpose
Oral Cavity Cancer
Status
Recruiting
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
Gross examination of the resection specimen
Frozen section
Sponsored by
About this trial
This is an interventional treatment trial for Oral Cavity Cancer focused on measuring Oral squamous Cell carcinoma, frozen section, local recurrence
Eligibility Criteria
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 -
Sites / Locations
- Tata Memorial HospitalRecruiting
- ACTREC,Advanced Centre for Treatment, Research and Education in Cancer
- Mahamana Pandit Madan Mohan Malaviya Cancer Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Gross examination
Frozen section
Arm Description
measurement of the surgical margins will be done by the surgeon in the operating room using sterile scale after resection of the primary tumor .
frozen section examination of surgical margins will be done by the pathologist.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of GE and FS for the assessment of surgical margin
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04809324
Brief Title
Gross Examinations Versus Frozen Section for Assessment of Surgical Margins in Oral Cancers
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 15, 2021 (Actual)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
June 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr.Pankaj Chaturvedi
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oral Cavity Cancer
Keywords
Oral squamous Cell carcinoma, frozen section, local recurrence
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Masking Description
patient and the treating clinician will not be aware of the randomisation allocation(gross examination or frozen section) prior to resection of the tumour specimen
Allocation
Randomized
Enrollment
1206 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Gross examination
Arm Type
Experimental
Arm Description
measurement of the surgical margins will be done by the surgeon in the operating room using sterile scale after resection of the primary tumor .
Arm Title
Frozen section
Arm Type
Active Comparator
Arm Description
frozen section examination of surgical margins will be done by the pathologist.
Intervention Type
Procedure
Intervention Name(s)
Gross examination of the resection specimen
Intervention Description
measurement of the surgical margin by the operating surgeon using sterile scale, margins <7mm will be revised on table
Intervention Type
Procedure
Intervention Name(s)
Frozen section
Intervention Description
frozen section evaluation of the specimen by the pathologist
Primary Outcome Measure Information:
Title
local recurrence free survival (LRFS) between two arms
Description
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
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Accuracy of gross examination
Description
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.
Time Frame
5 years
Title
Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of GE and FS for the assessment of surgical margin
Time Frame
5years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pankaj Chaturvedi, MS
Phone
+91 02224177189
Email
chaturvedi.pankaj@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Vidisha V Tuljapurkar, MS MCh
Phone
+91 02224177187
Email
vidishavt@yahoo.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pankaj Chaturvedi, MS
Organizational Affiliation
Tata Memorial Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tata Memorial Hospital
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
400012
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pankaj Chaturvedi, MS
Phone
+91 9869486912
Email
chaturvedi.pankaj@gmail.com
First Name & Middle Initial & Last Name & Degree
Deepa Nair, MS,DNB
Phone
+91 0222 02224177282
Email
drdeepanair78@gmail.com
Facility Name
ACTREC,Advanced Centre for Treatment, Research and Education in Cancer
City
Navi Mumbai
State/Province
Raigad
ZIP/Postal Code
-410210
Country
India
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sudhir Nair, MS
Phone
9769617780
Email
sudhirvr@gmail.com
Facility Name
Mahamana Pandit Madan Mohan Malaviya Cancer Centre
City
Varanasi
State/Province
Uttar Pradesh
ZIP/Postal Code
221005
Country
India
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Assem Mishra, MS,MCh
Phone
8080611946
Email
draseemmishra@gmail.com
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
IPD Sharing Time Frame
Beginning 3 months and ending 5 years following article publication.
IPD Sharing Access Criteria
Researchers who provide a methodologically sound proposal To achieve aims in the approved proposal for individual participant data meta-analysis.
Proposals should be directed to chaturvedi.pankaj@gmail.com. To gain access, data requestors will need to sign a data access agreement.
Citations:
PubMed Identifier
755803
Citation
Looser KG, Shah JP, Strong EW. The significance of "positive" margins in surgically resected epidermoid carcinomas. Head Neck Surg. 1978 Nov-Dec;1(2):107-11. doi: 10.1002/hed.2890010203.
Results Reference
background
PubMed Identifier
2221245
Citation
Loree TR, Strong EW. Significance of positive margins in oral cavity squamous carcinoma. Am J Surg. 1990 Oct;160(4):410-4. doi: 10.1016/s0002-9610(05)80555-0.
Results Reference
background
PubMed Identifier
3583852
Citation
Chen TY, Emrich LJ, Driscoll DL. The clinical significance of pathological findings in surgically resected margins of the primary tumor in head and neck carcinoma. Int J Radiat Oncol Biol Phys. 1987 Jun;13(6):833-7. doi: 10.1016/0360-3016(87)90095-2.
Results Reference
background
PubMed Identifier
19071037
Citation
Pathak KA, Nason RW, Penner C, Viallet NR, Sutherland D, Kerr PD. Impact of use of frozen section assessment of operative margins on survival in oral cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Feb;107(2):235-9. doi: 10.1016/j.tripleo.2008.09.028. Epub 2008 Dec 13.
Results Reference
background
PubMed Identifier
28159583
Citation
Mair M, Nair D, Nair S, Dutta S, Garg A, Malik A, Mishra A, Shetty Ks R, Chaturvedi P. Intraoperative gross examination vs frozen section for achievement of adequate margin in oral cancer surgery. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 May;123(5):544-549. doi: 10.1016/j.oooo.2016.11.018. Epub 2016 Dec 7.
Results Reference
background
PubMed Identifier
15183407
Citation
Kovacs AF. Relevance of positive margins in case of adjuvant therapy of oral cancer. Int J Oral Maxillofac Surg. 2004 Jul;33(5):447-53. doi: 10.1016/j.ijom.2003.10.015.
Results Reference
background
PubMed Identifier
3766863
Citation
Scholl P, Byers RM, Batsakis JG, Wolf P, Santini H. Microscopic cut-through of cancer in the surgical treatment of squamous carcinoma of the tongue. Prognostic and therapeutic implications. Am J Surg. 1986 Oct;152(4):354-60. doi: 10.1016/0002-9610(86)90304-1.
Results Reference
background
PubMed Identifier
11037842
Citation
DiNardo LJ, Lin J, Karageorge LS, Powers CN. Accuracy, utility, and cost of frozen section margins in head and neck cancer surgery. Laryngoscope. 2000 Oct;110(10 Pt 1):1773-6. doi: 10.1097/00005537-200010000-00039.
Results Reference
background
PubMed Identifier
9216496
Citation
Ord RA, Aisner S. Accuracy of frozen sections in assessing margins in oral cancer resection. J Oral Maxillofac Surg. 1997 Jul;55(7):663-9; discussion 669-71. doi: 10.1016/s0278-2391(97)90570-x.
Results Reference
background
PubMed Identifier
12729775
Citation
Ribeiro NF, Godden DR, Wilson GE, Butterworth DM, Woodwards RT. Do frozen sections help achieve adequate surgical margins in the resection of oral carcinoma? Int J Oral Maxillofac Surg. 2003 Apr;32(2):152-8. doi: 10.1054/ijom.2002.0262.
Results Reference
background
PubMed Identifier
30950438
Citation
Datta S, Mishra A, Chaturvedi P, Bal M, Nair D, More Y, Ingole P, Sawakare S, Agarwal JP, Kane SV, Joshi P, Nair S, D'Cruz A. Frozen section is not cost beneficial for the assessment of margins in oral cancer. Indian J Cancer. 2019 Jan-Mar;56(1):19-23. doi: 10.4103/ijc.IJC_41_18.
Results Reference
background
PubMed Identifier
23765548
Citation
Chaturvedi P, Datta S, Nair S, Nair D, Pawar P, Vaishampayan S, Patil A, Kane S. Gross examination by the surgeon as an alternative to frozen section for assessment of adequacy of surgical margin in head and neck squamous cell carcinoma. Head Neck. 2014 Apr;36(4):557-63. doi: 10.1002/hed.23313. Epub 2013 Jun 14.
Results Reference
background
PubMed Identifier
30912991
Citation
Bulbul MG, Tarabichi O, Sethi RK, Parikh AS, Varvares MA. Does Clearance of Positive Margins Improve Local Control in Oral Cavity Cancer? A Meta-analysis. Otolaryngol Head Neck Surg. 2019 Aug;161(2):235-244. doi: 10.1177/0194599819839006. Epub 2019 Mar 26.
Results Reference
background
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Gross Examinations Versus Frozen Section for Assessment of Surgical Margins in Oral Cancers
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