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

NCT04809324 | Recruiting

• 2 other identifiers: protocol no 3541CTRI/2021/03/032015
• Study Type: interventional
• Target: 1,206
• Locations: 1 country
• Sites: 3

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.

Conditions

Oral Cavity Cancer

Keywords

Oral squamous Cell carcinoma; frozen section; local recurrence

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Accuracy of gross examination

  5 years

• Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of GE and FS for the assessment of surgical margin

  5years

Study Arms (2)

Gross examination

EXPERIMENTAL

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

Frozen section

ACTIVE COMPARATOR

frozen section examination of surgical margins will be done by the pathologist.

Procedure: Frozen section

Interventions

Gross examination of the resection specimen PROCEDURE

measurement of the surgical margin by the operating surgeon using sterile scale, margins \<7mm will be revised on table

Gross examination

Frozen section PROCEDURE

frozen section evaluation of the specimen by the pathologist

Frozen section

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Multifocal disease
• Clinically evident field cancerization
• Previous treatment for oral cavity cancer - Surgery /chemo or radiotherapy -

Sponsors & Collaborators

• Dr.Pankaj Chaturvedi: lead

Study Sites (3)

Tata Memorial Hospital

Mumbai, Maharashtra, 400012, India

RECRUITING

ACTREC,Advanced Centre for Treatment, Research and Education in Cancer

Navi Mumbai, Raigad, -410210, India

RECRUITING

Mahamana Pandit Madan Mohan Malaviya Cancer Centre

Varanasi, Uttar Pradesh, 221005, India

RECRUITING

Related Publications (13)

• 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.

  PMID: 755803 BACKGROUND

• 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.

  PMID: 2221245 BACKGROUND

• 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.

  PMID: 3583852 BACKGROUND

• 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.

  PMID: 19071037 BACKGROUND

• 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.

  PMID: 28159583 BACKGROUND

• 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.

  PMID: 15183407 BACKGROUND

• 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.

  PMID: 3766863 BACKGROUND

• 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.

  PMID: 11037842 BACKGROUND

• 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.

  PMID: 9216496 BACKGROUND

• 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.

  PMID: 12729775 BACKGROUND

• 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.

  PMID: 30950438 BACKGROUND

• 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.

  PMID: 23765548 BACKGROUND

• 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.

  PMID: 30912991 BACKGROUND

MeSH Terms

Conditions

Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Frozen Sections

Condition Hierarchy (Ancestors)

Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Cryoultramicrotomy; Microtomy; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques

Study Officials

• Pankaj Chaturvedi, MS

  Tata Memorial Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pankaj Chaturvedi, MS

CONTACT

+91 02224177189; chaturvedi.pankaj@gmail.com

Vidisha V Tuljapurkar, MS MCh

CONTACT

+91 02224177187; vidishavt@yahoo.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr Pankaj Chaturvedi ,Prof. and Surgeon, Dept of Head Neck Surgery

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: March 22, 2021
• Study Start: November 15, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 11, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• 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.

Locations

IN (3)