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. 2024 Feb 1;150(2):107-116.
doi: 10.1001/jamaoto.2023.3952.

Oncologic Safety of Close Margins in Patients With Low- to Intermediate-Grade Major Salivary Gland Carcinoma

Mirabelle Sajisevi  1 , Kenny Nguyen  2 , Peter Callas  2 , Andrew J Holcomb  3 , Emre Vural  4 , Kyle P Davis  5 , Carissa M Thomas  6 , Karolina A Plonowska-Hirschfeld  7 , John S Stein  6 , Antoine Eskander  8   9 , Kiran Kakarala  10 , Danny J Enepekides  8 , Michael P Hier  11 , William R Ryan  7 ; American Head and Neck Society Salivary Gland Section; Ameya A Asarkar  12 , Ricardo Aulet  13 , Rebecca K Bell  14 , Michael A Blasco  15 , Vanessa B Bowmaster  16 , Clayton P Burruss  17 , Jeffson Chung  18 , Kimberly Chan  19 , Brent A Chang  20 , Charles S Coffey  21 , David M Cognetti  22 , Dylan J Cooper  15 , Joehassin Cordero  23 , John Donovan  24 , Yue Jennifer Du  25 , Yusuf Dundar  23 , Rogerio A Dedivitis  26 , Heather A Edwards  27 , Boban M Erovic  28 , Philip A Feinberg  29 , Emily A Garvey  30 , David P Goldstein  31 , Joseph F Goodman  32 , Rafael N Goulart  33 , Neerav Goyal  19 , Stefan Grasl  34 , Jonathan P Giurintano  35 , Nikita Gupta  17 , Andy M Habib  35 , Trevor G Hackman  36 , Jared H Hara  37 , Christina Henson  38 , Michael L Hinni  20 , Nadia Hua  39 , Stephanie Johnson-Obaseki  39 , Aditya Juloori  37 , Noah S Kalman  40 , Alexandra E Kejner  41 , Sobia F Khaja  42 , Jamie A Ku  43 , Arnaud Lambert  44 , Bao K Luu  21 , Kelly R Magliocca  45 , Luiz R Medina Dos Santos  33 , Cara Michael  27 , Brett A Miles  15 , Giulianno Molina de Melo  46   47 , Michael G Moore  48 , Gregoire B Morand  44 , Kauê Moura  49 , Laith Mukdad  50 , Hesameddin Noroozi  31 , Rusha Patel  51 , Joseph A Paydarfar  14 , Nader Sadeghi  44 , Fabrice N Savaria  52 , Nicole C Schmitt  53 , Justin Shapiro  54 , Timothy B Shaver  32 , Sandro J Stoeckli  52 , Maie St John  50 , William Alvo Stokes  18 , Anita Sulibhavi  55 , Jason Tasoulas  36 , Varun Vendra  55 , Daniel B Vinh  48 , Celina G Virgen  10 , Christian Wooten  50 , Neil M Woody  56 , Geoffrey D Young  40
Affiliations

Oncologic Safety of Close Margins in Patients With Low- to Intermediate-Grade Major Salivary Gland Carcinoma

Mirabelle Sajisevi et al. JAMA Otolaryngol Head Neck Surg. .

Abstract

Importance: Postoperative radiation therapy for close surgical margins in low- to intermediate-grade salivary carcinomas lacks multi-institutional supportive evidence.

Objective: To evaluate the oncologic outcomes for low- and intermediate-grade salivary carcinomas with close and positive margins.

Design, setting, and participants: The American Head and Neck Society Salivary Gland Section conducted a retrospective cohort study from 2010 to 2019 at 41 centers. Margins were classified as R0 (negative), R1 (microscopically positive), or R2 (macroscopically positive). R0 margins were subclassified into clear (>1 mm) or close (≤1 mm). Data analysis was performed from June to October 2023.

Main outcomes and measures: Main outcomes were risk factors for local recurrence.

Results: A total of 865 patients (median [IQR] age at surgery, 56 [43-66] years; 553 female individuals [64%] and 312 male individuals [36%]) were included. Of these, 801 (93%) had parotid carcinoma and 64 (7%) had submandibular gland carcinoma, and 748 (86%) had low-grade tumors and 117 (14%) had intermediate-grade tumors, with the following surgical margins: R0 in 673 (78%), R1 in 168 (19%), and R2 in 24 (3%). Close margins were found in 395 of 499 patients with R0 margins (79%), for whom margin distances were measured. A total of 305 patients (35%) underwent postoperative radiation therapy. Of all 865 patients, 35 (4%) had local recurrence with a median (IQR) follow-up of 35.3 (13.9-59.1) months. In patients with close margins as the sole risk factor for recurrence, the local recurrence rates were similar between those who underwent postoperative radiation therapy (0 of 46) or observation (4 of 165 [2%]). Patients with clear margins (n = 104) had no recurrences. The local recurrence rate in patients with R1 or R2 margins was better in those irradiated (2 of 128 [2%]) compared to observed (13 of 64 [20%]) (hazard ratio [HR], 0.05; 95% CI, 0.01-0.24). Multivariable analysis for local recurrence found the following independent factors: age at diagnosis (HR for a 10-year increase in age, 1.33; 95% CI, 1.06-1.67), R1 vs R0 (HR, 5.21; 95% CI, 2.58-10.54), lymphovascular invasion (HR, 4.47; 95% CI, 1.43-13.99), and postoperative radiation therapy (HR, 0.10; 95% CI, 0.04-0.29). The 3-year local recurrence-free survivals for the study population were 96% vs 97% in the close margin group.

Conclusions and relevance: In this cohort study of patients with low- and intermediate-grade major salivary gland carcinoma, postoperative radiation therapy for positive margins was associated with decreased risk of local recurrence. In isolation from other risk factors for local recurrence, select patients with close surgical margins (≤1 mm) may safely be considered for observation.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Cognetti reported personal fees from Rakuten Medical outside the submitted work. Dr Hinni reported personal fees from Karl Storz (employer licensed a design for a laryngoscope) outside the submitted work. Dr Juloori reported grants and personal fees from AstraZeneca outside the submitted work. Dr Schmitt reported grants from Astex Pharmaceuticals and personal fees from Sensorion and Checkpoint Surgical outside the submitted work. Dr Ryan reported personal fees from Olympus, Rakuten Medical, and Intuitive outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Overall Survival and Disease-Specific Survival Stratified by Margin Status
Figure 2.
Figure 2.. Kaplan-Meier Curve for Local Control Stratified by Adjuvant Radiotherapy in Patients With Negative Margins and Positive Margins
Figure 3.
Figure 3.. Local Recurrence-Free Survival in Close Margin Group Stratified by Adjuvant Radiotherapy
See this image and copyright information in PMC

Comment in

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