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

Oral Cavity Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04809324
• Other study ID #: protocol no 3541
• Secondary ID: CTRI/2021/03/032
• Status: Recruiting
• Phase: N/A
• Start date: November 15, 2021
• Est. completion date: June 2028

Study information

• Verified date: November 2023
• Source: Tata Memorial Centre
• Contact: Pankaj Chaturvedi, MS
• Phone: +91 02224177189
• Email: chaturvedi.pankaj[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1206
• Est. completion date: June 2028
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

1. Biopsy proven treatment naïve cases of OCSCC who are planned for curative surgery with en-bloc removal of the tumor with adequate margin

2. In detail assessment of the primary tumor is possible pre-operatively

3. Written informed consent

4. Age more than 18 years

Exclusion Criteria:

1. Multifocal disease

2. Clinically evident field cancerization

3. Previous treatment for oral cavity cancer - Surgery /chemo or radiotherapy -

Related Conditions & MeSH terms

• Mouth Neoplasms
• Oral Cavity Cancer

Intervention

Procedure:
• Gross examination of the resection specimen
measurement of the surgical margin by the operating surgeon using sterile scale, margins <7mm will be revised on table
• Frozen section
frozen section evaluation of the specimen by the pathologist

Locations

Country	Name	City	State
India	Tata Memorial Hospital	Mumbai	Maharashtra
India	ACTREC,Advanced Centre for Treatment, Research and Education in Cancer	Navi Mumbai	Raigad
India	Mahamana Pandit Madan Mohan Malaviya Cancer Centre	Varanasi	Uttar Pradesh

Sponsors (1)

Lead Sponsor	Collaborator
Dr.Pankaj Chaturvedi

Country where clinical trial is conducted

India, 

References & Publications (13)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of GE and FS for the assessment of surgical margin		5years