Oral Cavity CancerNCT04809324
Gross Examinations Versus Frozen Section for Assessment of Surgical Margins in Oral Cancers
A study testing Gross examination of the resection specimen and Frozen section in people with Oral Cavity Cancer, run by Dr.Pankaj Chaturvedi at 3 sites in India.
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Oral Cavity Cancer
- What is being tested?
- Gross examination of the resection specimen and Frozen section
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,206 participants
- Where
- 3 sitesIndia
- Study dates
- 15 Nov 2021to Jun 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Multifocal disease
- Clinically evident field cancerization
- Previous treatment for oral cavity cancer - Surgery /chemo or radiotherapy -
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
India3 sites, 3 recruiting
- Recruiting
Tata Memorial Hospital
Mumbai, Maharashtra, 400012
Pankaj Chaturvedi, MS, +91 9869486912, chaturvedi.pankaj@gmail.com
Deepa Nair, MS,DNB, +91 0222 02224177282, drdeepanair78@gmail.com
- Recruiting
ACTREC,Advanced Centre for Treatment, Research and Education in Cancer
Navi Mumbai, Raigad, -410210
Sudhir Nair, MS, 9769617780, sudhirvr@gmail.com
- Recruiting
Mahamana Pandit Madan Mohan Malaviya Cancer Centre
Varanasi, Uttar Pradesh, 221005
Assem Mishra, MS,MCh, 8080611946, draseemmishra@gmail.com
About this study
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
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
- Being tested
- Gross examination of the resection specimen, Frozen section
- Keywords
- Oral squamous Cell carcinoma, frozen section, local recurrence
- Medical subject headings
- Mouth Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gross examination of the resection specimenProcedure or surgery
measurement of the surgical margin by the operating surgeon using sterile scale, margins <7mm will be revised on table
Frozen sectionProcedure or surgery
frozen section evaluation of the specimen by the pathologist
| Study group | Role | What they receive |
|---|---|---|
| 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 . Receives: Procedure: Gross examination of the resection specimen |
| Frozen section | Active comparator | frozen section examination of surgical margins will be done by the pathologist. Receives: Procedure: Frozen section |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years
Secondary outcomes (2)
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.
Measured: 5 years
Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of GE and FS for the assessment of surgical margin
Measured: 5years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2021
- Study start15 Nov 2021
- Primary completionDec 2026 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Oral Cavity CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 1,206 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dr.Pankaj Chaturvedi
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr.Pankaj Chaturvedi, Tata Memorial Centre
- Investigators
- Pankaj Chaturvedi, MS, Principal investigator, Tata Memorial Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04809324
- Sponsor's protocol ID
- protocol no 3541
- Other IDs
- CTRI/2021/03/032015
- Status last verified
- Apr 2025
- First submitted
- 18 Mar 2021
- Last updated
- 11 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Publications
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.
PubMed 755803Loree 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.
PubMed 2221245Chen 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.
PubMed 3583852Pathak 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.
PubMed 19071037Mair 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.
PubMed 28159583Kovacs 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.
PubMed 15183407Scholl 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.
PubMed 3766863DiNardo 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.
PubMed 11037842Ord 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.
PubMed 9216496Ribeiro 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.
PubMed 12729775Datta 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.
PubMed 30950438Chaturvedi 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.
PubMed 23765548Bulbul 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.
PubMed 30912991
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04809324
- Acronym / sponsor ID
- protocol no 3541
- Conditions
- Oral Cavity Cancer
- Keywords
- Oral squamous Cell carcinoma, frozen section, local recurrence
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,206 participants (estimated)
- Lead sponsor
- Dr.Pankaj ChaturvediUniversity, hospital or other
- Study start
- 15 Nov 2021 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 22 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gross examination | Experimental | Procedure: Gross examination of the resection specimenmeasurement 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 | Active comparator | Procedure: Frozen sectionfrozen section examination of surgical margins will be done by the pathologist. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- Multifocal disease
- Clinically evident field cancerization
- Previous treatment for oral cavity cancer - Surgery /chemo or radiotherapy -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gross examination of the resection specimenmeasurement of the surgical margin by the operating surgeon using sterile scale, margins <7mm will be revised on table | Procedure or surgery | Gross examination |
| Frozen sectionfrozen section evaluation of the specimen by the pathologist | Procedure or surgery | Frozen section |
Primary outcome
local recurrence free survival (LRFS) between two arms
Time frame: 2 years
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 secondary outcomes
Accuracy of gross examination
Time frame: 5 years
Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of GE and FS for the assessment of surgical margin
Time frame: 5years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2025.
- Background: PubMed 755803Looser 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.
- Background: PubMed 2221245Loree 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.
- Background: PubMed 3583852Chen 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.
- Background: PubMed 19071037Pathak 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.
- Background: PubMed 28159583Mair 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.
- Background: PubMed 15183407Kovacs 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.
- Background: PubMed 3766863Scholl 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.
- Background: PubMed 11037842DiNardo 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.
- Background: PubMed 9216496Ord 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.
- Background: PubMed 12729775Ribeiro 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.
- Background: PubMed 30950438Datta 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.
- Background: PubMed 23765548Chaturvedi 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.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Pankaj Chaturvedi, MS principal investigator
Tata Memorial Centre
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Gross examination of the resection specimen and Frozen section in people with Oral Cavity Cancer, run by Dr.Pankaj Chaturvedi at 3 sites in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Pankaj Chaturvedi, MS (+91 02224177189, chaturvedi.pankaj@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
local recurrence free survival (LRFS) between two arms (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04809324, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2025.