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

Официальное название

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

Обзор

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.

Вмешательства

• Процедура 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
• Процедура Frozen section
  frozen section evaluation of the specimen by the pathologist

Первичные конечные точки

• local recurrence free survival (LRFS) between two arms [Срок оценки: 2 years]

Вторичные конечные точки (2)

• Accuracy of gross examination [Срок оценки: 5 years]
• Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of GE and FS for the assessment of surgical margin [Срок оценки: 5years]

Критерии участия

Критерии включения

• 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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Индия · 3 центра

• Tata Memorial Hospital — Mumbai
• ACTREC,Advanced Centre for Treatment, Research and Education in Cancer — Navi Mumbai
• Mahamana Pandit Madan Mohan Malaviya Cancer Centre — Varanasi

Публикации

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT04809324 · protocol no 3541 · CTRI/2021/03/032015

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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