Abstract
Background and Objectives
To determine locoregional recurrence rate (LRR) and disease‐specific survival (DSS) following marginal vs segmental mandibulectomy.
Methods
Included were 210 patients, who had marginal or segmental mandibulectomy between 2000 and 2017. Marginal resection was performed when complete removal of the tumor was deemed feasible on the condition that at least 1 cm bone height of the inferior border of the mandible could be preserved. Segmental resection was performed in case less than 1 cm bone height of the mandible would remain. Clinical and histopathological data were collected from medical records. LRR and DSS were computed using Kaplan‐Meier analysis. Cox‐regression analysis was used to identify risk factors for LRR and DSS.
Results
A total of 59 marginal and 151 segmental resections had been performed. There was no significant difference in 3‐ and 5‐year LRR (P = .904) and no significant difference in 3‐ and 5‐year DSS (P = .362) between the marginal and segmental resection group. Cox‐regression analysis showed a trend for surgical margin less than equal to 1 mm, to affect LRR (P = .05) and surgical margin less than equal 1 mm, perineural invasion and lymph node metastasis to affect DSS (P < .05).
Conclusions
There was no difference in outcome between the two types of mandibulectomy.
Keywords: bone invasion, fracture, mandibulectomy, oral cancer, osteoradionecrosis, protocol
1. INTRODUCTION
Each year approximately 300 000 new cases of oral cancer are diagnosed worldwide. 1 Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity. 1 OSCC can invade the mandible when located in close proximity to the bone. Surgery is the first‐choice treatment for OSCC, with the aim to completely remove the tumor. If OSCC invades the mandible, the affected bone needs to be resected in continuity with the tumor in the soft tissues. There are two types of mandibular resection: segmental resection and marginal resection. Segmental resection is a resection involving the entire vertical height of the mandible with interruption of the continuity of the mandible. Marginal resection is a resection involving part of the height of the mandible with preservation of the continuity of the mandible. The indication for segmental resection and marginal resection is often debated, as well as the extent of the resection. 2 , 3 , 4 , 5 , 6 There is no guideline based on evidence, that could assist in the decision about the type of mandibular resection. A future guideline should be oncologically safe on the one hand to minimize the risk of irradical resection and avoid unnecessary removal of bone, on the other hand, to preserve function, aesthetics, and quality of life. 2 To develop such a guideline, outcomes are necessary, like locoregional recurrence rate (LRR) and disease‐specific survival (DSS) following marginal and segmental resection for OSCC.
The aim of this study is to determine LRR and DSS in patients who underwent marginal and segmental resection for OSCC with the histopathologically confirmed invasion of mandibular bone. Our hypothesis is that there is no difference in LRR and DSS between patients who underwent marginal and segmental resection for OSCC with the histopathologically confirmed invasion of mandibular bone.
2. MATERIALS AND METHODS
2.1. Study design, inclusion, and exclusion criteria
A retrospective cohort study was conducted. This study was exempted from an ethical review of the University Medical Center Utrecht (Reg.No: 19‐401/C).
Included were patients who had undergone marginal or segmental resection at a single center with a head and neck cancer service, the University Medical Center Utrecht, between January 2000 and December 2017 for first primary OSCC, with mandibular invasion confirmed by histopathological examination of the resection specimen.
Excluded were patients lost to follow up within 12 months, and patients with missing clinical or histopathological information other than invasive growth pattern or tumor grade.
2.2. Preoperative assessment
For preoperative screening, we performed orthopantomogram (OPT), computed tomography or magnetic resonance imaging, and bone single photon emission computed tomography (SPECT) on the indication. The extensive bone invasion was made visible on the OPT, whereas computed tomography or magnetic resonance imaging could reveal more subtle bone invasion. On indication bone, SPECT was used to rule out mandibular invasion, as bone SPECT has 100% sensitivity, as described in a previous publication. 4
2.3. Treatment protocol for the type of mandibular resection
Marginal resection was performed when complete removal of the tumor in the bone and soft tissues was deemed feasible, on the condition that at least 1 cm bone height of the inferior border of the mandible could be preserved. Segmental resection was performed in case less than 1 cm bone height of the inferior border of the mandible was estimated to remain.
2.4. Data collection
The following data were collected from medical records: sex, age, tumor location, tumor size (largest diameter measured in any direction), infiltration depth, tumor grade, invasive growth pattern, vascular or lymphovascular invasion, perineural invasion, lymph node metastasis, type of mandibular resection, surgical margin (≤1 and >1 mm), adjuvant therapy, date of locoregional recurrence, date of distant metastasis, date, and cause of death. Brown's classification for segmental mandibular defects was used to classify the segmental resections and the location of the corresponding tumors. Because no system exists to classify marginal mandibular defects, we used Brown's classification also for marginal resections to classify the horizontal position of the corresponding tumors. In case osteoradionecrosis (ORN) or fracture occurred after marginal resection, additional data were collected: sex, age, date of diagnosis, area of ORN or fracture, cause of ORN or fracture, the height of the remaining mandible, and preservation of the inferior alveolar nerve.
2.5. Statistical analyses
Statistical analyses were run using SPSS software for Windows (IBM SPSS Statistics, Version 25.0. Armonk, NY). The distribution of several variables was compared using the χ 2 test or independent t test. DSS was defined as the time from diagnosis until death or date last seen alive and was estimated by Kaplan‐Meier analysis. To compare survival curves, the log rank (Mantel‐Cox) test was used. Cox regression analysis was used to identify factors associated with LRR and DSS. Statistical significance was set at P < .05.
3. RESULTS
Between January 2000 and December 2017, 229 patients had undergone mandibular resection for OSCC with mandibular bone invasion confirmed by histopathological examination of the resection specimen. Nineteen of the 229 patients with mandibular invasion were lost to follow‐up within 12 months. The remaining 210 patients were included in the study. From these 210 patients, 59 patients had a marginal resection and 151 had a segmental resection.
Table 1 shows the baseline characteristics of the study population.
Table 1.
Clinical data (patient and tumor variables), distribution over marginal and segmental resection group
| Number | Marginal resection | Segmental resection | P value | |
|---|---|---|---|---|
| Sex | .095 | |||
| Male | 127 | 41 (32.28%) | 86 (67.72%) | |
| Female | 83 | 18 (21.69%) | 65 (78.31%) | |
| Age | .460 * | |||
| Mean (SD) | 66.53 (10.73) | 65.17 (12.37) | ||
| Tumor location | ||||
| (Brown's classification) | .000 | |||
| I | 66 | 32 (48.48%) | 34 (51.51% | |
| Ic | 3 | 0 (0.00%) | 3 (100%) | |
| II | 58 | 3 (5.17%) | 55 (94.83%) | |
| III | 58 | 23 (39.66%) | 35 (60.34%) | |
| IV | 25 | 1 (4.00%) | 24 (96.00%) | |
| Tumor size, mm | .001 * | |||
| Mean (SD) | 30.09 (13.50) | 38.50 (16.50) | ||
| Infiltration depth (mm) | .000 * | |||
| Mean (SD) | 12.18 (7.01) | 21.21 (13.17) | ||
| Tumor grade | .242 | |||
| Well | 27 | 6 (22.22%) | 21 (77.78%) | |
| Moderate | 128 | 37 (28.91%) | 91 (71.09%) | |
| Poor | 17 | 2 (11.76%) | 15 (88.24%) | |
| Unknown | 38 | 14 (36.84%) | 24 (63.16%) | |
| Invasive growth pattern | .371 | |||
| Cohesive | 32 | 8 (25.00%) | 24 (75.00%) | |
| Unfavorable | 114 | 31 (27.19%) | 83 (72.81%) | |
| Remaining | 5 | 0 (0.00%) | 5 (100%) | |
| Unknown | 59 | 20 (33.90%) | 39 (66.10%) | |
| Vascular/lymphovascular invasion | .666 | |||
| Yes | 32 | 10 (31.25%) | 22 (68.75%) | |
| No | 178 | 49 (27.53%) | 129 (72.47%) | |
| Perineural invasion | .715 | |||
| Yes | 99 | 29 (29.29%) | 70 (70.70%) | |
| No | 111 | 30 (27.03%) | 81 (72.97%) | |
| Lymph node metastasis | .721 | |||
| Yes | 118 | 32 (27.12%) | 86 (72.88%) | |
| No | 92 | 27 (29.35%) | 65 (70.65%) | |
| Surgical margin | .118 | |||
| >1 mm | 128 | 31 (24.22%) | 97 (75.78%) | |
| ≤1 mm | 82 | 28 (34.15%) | 54 (65.85%) | |
| Adjuvant therapy | .187 | |||
| Radiotherapy | 136 | 42 (30.88%) | 94 (69.12%) | |
| Chemoradiation | 23 | 4 (17.39%) | 19 (82.61%) | |
| No adjuvant therapy | 51 | |||
| Deceased | .721 | |||
| Yes | 118 | 32 (27.12%) | 86 (72.88%) | |
| No | 92 | 27 (29.35%) | 65 (70.65%) | |
| Cause of death | .515 | |||
| Tumor‐related | 76 | 19 (25.00%) | 57 (75.00%) | |
| Other | 23 | 9 (39.13%) | 14 (60.87%) | |
| Unknown | 19 | 4 (21.05%) | 15 (78.95%) |
Note: P < .05 is significant (bold). The χ 2 test performed;
Expect independent t test.
Sex, age, tumor grade, invasive growth pattern, vascular or lymphovascular invasion, perineural invasion, lymph node metastasis, surgical margin, adjuvant therapy, and cause of death were evenly distributed between the marginal and segmental resection group. Tumor location, tumor size and infiltration depth (mm) were unevenly distributed between the marginal and segmental resection group: the segmental resection group contained more mandibular defects classified as Brown's class Ic, II, and IV (P = .000), larger tumors (P = .001) and tumors with increased infiltration depth (P = .000) than the marginal resection group. In this study population, there were no mandibular defects classified as Brown's class IIc and IVc.
3.1. Locoregional recurrence rate
Three‐year LRR was 20.3% in the marginal resection group and 21.9% in the segmental resection group (P = .716) (Figure 1 and Table 2). The 5‐year LRR was 22.0% in the marginal resection group and 23.2% in the segmental resection group (P = .783) (Figure 1 and Table 2). The log rank test showed no significant difference in LRR between the marginal and segmental resection group (P = .904).
Figure 1.
Locoregional recurrence (Kaplan‐Meier) [Color figure can be viewed at wileyonlinelibrary.com]
Table 2.
Kaplan‐Meier estimated locoregional recurrence rate and disease‐specific survival
| LRR | Three‐y LRR this study vs literature | Five‐y LRR this study vs literature |
|---|---|---|
| Marginal resection | 20.3% vs 25.0‐29.1% 7 , 8 | 22.0% vs 17‐39.7% 7 , 9 |
| Segmental resection | 21.9% vs 18.4% 7 | 23.2% vs 14‐34.2% 7 , 9 |
| P value | .716/n.a. | .783/n.a. |
| DSS | Three‐y DSS this study vs literature | Five‐y DSS this study vs literature |
|---|---|---|
| Marginal resection | 72.9% vs 75.2% 7 | 69.5% vs 55.5% 7 |
| Segmental resection | 66.2% vs 69.2% 7 | 64.2% vs 60.7% 7 |
| P value | .287/n.a. | .391/n.a. |
Abbreviations: DSS, disease‐specific survival; LRR, locoregional recurrence rate; NA, not applicable.
Cox regression analysis showed a trend for a surgical margin less than equal to 1 mm to affect LRR (P = .05) (Table 3).
Table 3.
Cox regression to analyze potentially predictive factors for locoregional recurrence rate
| Potentially predictive factors | Hazard ratio (95% CI) | P value |
|---|---|---|
| Sex | 0.677 (0.358‐1.280) | .230 |
| Age | 0.996 (0.967‐1.025) | .771 |
| Tumor size | 1.013 (0.995‐1.032) | .154 |
| Infiltration depth | 1.004 (0.978‐1.032) | .749 |
| Lymph node metastasis | 0.886 (0.462‐1.697) | .714 |
| Tumor grade | .313 | |
| Vascular/lymphovascular invasion | 0.716 (0.316‐1.620) | .422 |
| Perineural invasion | 0.888 (0.449‐1.754) | .732 |
| Type of mandibular resection | 0.931 (0.447‐1.937) | .848 |
| Surgical margin ≤1 mm | 1.888 (0.999‐3.570) | .050 |
| Adjuvant therapy | 1.003 (0.426‐2.362) | .994 |
Note: P = .05 is a trend (bold).
3.2. Disease‐specific survival
Three‐year DSS was 72.9% in the marginal resection group and 66.2% in the segmental resection group (P = .287) (Figure 2 and Table 2). Five‐year DSS was 69.5% in the marginal resection group and 64.2% in the segmental resection group (P = .391) (Figure 2 and Table 2). The log‐rank test showed no significant difference in DSS between the marginal and segmental resection group (P = .362). Cox regression analysis showed that DSS was affected by a surgical margin less than equal to 1 mm (P = .003), perineural invasion (P = .013), and lymph node metastasis (P = .015) (Table 4).
Figure 2.
Disease‐specific survival (Kaplan‐Meier) [Color figure can be viewed at wileyonlinelibrary.com]
Table 4.
Cox regression to analyze potentially predictive factors for disease‐specific survival
| Potentially predictive factors | Hazard ratio (95% CI) | P value |
|---|---|---|
| Sex | 0.954 (0.510‐1.784) | .884 |
| Age | 0.990 (0.962‐1.018) | .466 |
| Tumor location (Brown's classification) | .563 | |
| Tumor size | 1.008 (0.991‐1.026) | .337 |
| Infiltration depth | 1.002 (0.978‐1.028) | .854 |
| Lymph node metastasis | 0.399 (0.190‐0.837) | .015 |
| Tumor grade | .294 | |
| Vascular/lymphovascular invasion | 0.974 (0.462‐2.050) | .944 |
| Perineural invasion | 0.431 (0.222‐0.838) | .013 |
| Type of mandibular resection | 0.529 (0.236‐1.185) | .122 |
| Surgical margin ≤1 mm | 2.631 (1.401‐4.940) | .003 |
| Adjuvant therapy | 1.192 (0.518‐2.741) | .680 |
Note: P < .05 is significant (bold).
3.3. Osteoradionecrosis and fracture after marginal resection
In 5 out of 59 patients who had a marginal resection, ORN, and/or fracture occurred. The pertinent data are shown in Table 5. Two patients had ORN, one patient had a mandibular fracture and two patients had ORN with pathological fracture. In four cases, the marginal resection had been made with the right angle. The remaining height of mandible after marginal resection ranged between 10 and 17 mm and the inferior alveolar nerve had been killed in one case.
Table 5.
Osteoradionecrosis and fracture after marginal resection
| ORN/# | Sex | Age, y | PORT | Time until ORN/#, mo | Area of ORN/# | Cause of ORN/# | Remaining bone height, mm | Preservation of inferior alveolar nerve |
|---|---|---|---|---|---|---|---|---|
| ORN | f | 49 | Yes | 25 | Anterior | Dental implant | 17 | Yes |
| ORN | f | 66 | Yes | 7 | Body | Right angle a | 13 | Yes |
| # | m | 63 | Yes | 26 | Body | Right angle b | 10 | No |
| ORN+# | m | 63 | Yes | 28 | Body | Right angle a | 10 | Yes |
| ORN+# | m | 66 | Yes | 23 | Body | Right angle b | 14 | Yes |
Note: #, fracture; Anterior, anterior mandible; Body, mandibular body.
Abbreviations: ORN, osteoradionecrosis; PORT: postoperative radiotherapy.
Means marginal resection performed with the right angle, combined with a mandibular split osteotomy.
Means marginal resection performed with the right angle.
4. DISCUSSION
Our hypothesis is confirmed in our study group that there was no difference in 3‐ and 5‐year LRR and 3‐ and 5‐year DSS between patients who underwent marginal resection or segmental resection for OSCC with histopathologically confirmed mandibular invasion; marginal resection was performed on the condition that 1 cm of bone height was preserved.
4.1. Locoregional recurrence rate
LRR in our study group was comparable with figures reported in the literature 7 , 10 , 11 (Table 2). We found no difference in LRR between the marginal and segmental resection group in patients with bone invasion of the mandible. This finding is in accordance with previous studies. 7 , 9 , 10 , 11 Our study showed a trend for surgical margin less than equal to 1 mm to affect LRR (P = .05), whereas Guerra et al 12 found a significant association between positive margin and tumor size and LRR.
4.2. Disease‐specific survival
DSS in our study was comparable with the figures reported in the literature 7 (Table 2).
We found no difference in DSS between the marginal and segmental resection group in patients with bone invasion of the mandible. This finding is in accordance with previous studies. 8 , 9 , 11 , 13 Our study showed that DSS was affected by a surgical margin (P = .003), perineural invasion (P = .013), and lymph node metastasis (P = .015). Other studies reported that survival was associated with tumor location, 14 tumor size, 15 tumor grade, 7 , 14 tumor stage, 8 , 14 lymph node metastasis 14 and positive margins. 8 , 14
4.3. Type of resection
Current knowledge of mandibular resection is mainly based on studies with low level of evidence such as retrospective studies, nonrandomized studies or case‐series. 6 , 7 , 8 Our study also had a retrospective design, and inherent to the retrospective design of the study was the different composition of the two groups: the segmental resection group had larger tumors and increased infiltration depth than the marginal resection group. The different composition of the groups hampers comparison of the treatment effect, which is the outcome after marginal vs segmental resection. Nonetheless, the outcomes following marginal resection for OSCC invading the mandible were not worse than following segmental resection, and increased infiltration depth did not correlate with LRR or DSS. The finding that there was no difference in outcome between the marginal and segmental resection group, might indirectly indicate that marginal resection can be oncologically safe when complete removal of the tumor is deemed feasible and at least 1 cm bone height of the inferior border of the mandible is preserved. We recommend segmental resection if less than 1 cm bone height of the mandible would remain.
In the future, a prospective study, ideally a randomized controlled trial, could be carried out to compare the outcomes of the two types of mandibular resection with a higher level of evidence.
5. CONCLUSION
There was no difference in LRR and DSS between marginal and segmental resection for OSCC invading the mandible. Marginal resection can be safe when complete removal of the tumor is deemed feasible and at least 1 cm bone height of the inferior border of the mandible is preserved. We recommend segmental resection if less than 1 cm bone height of the mandible would remain. Perineural invasion, lymph node metastasis, and surgical margin less than equal to 1 mm affected DSS of patients with OSCC and mandibular invasion.
SYNOPSIS
This study showed no difference in outcome between marginal and segmental mandibular resection. Marginal resection can be safe when complete removal of the tumor is deemed feasible and at least 1 cm bone height of the inferior border of the mandible is preserved. We recommend segmental resection if less than 1 cm bone height of the mandible would remain.
Stoop CC, de Bree R, Rosenberg AJWP, van Gemert JTM, Forouzanfar T, Van Cann EM. Locoregional recurrence rate and disease‐specific survival following marginal vs segmental resection for oral squamous cell carcinoma with mandibular bone invasion. J Surg Oncol. 2020;122:646–652. 10.1002/jso.26054
DATA AVAILABILITY STATEMENT
The datasets generated during and/or analyzed during the current study are not publicly available due to institutional restrictions but are available from the corresponding author on reasonable request.
REFERENCES
- 1. Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144:1941‐1953. [DOI] [PubMed] [Google Scholar]
- 2. Van Cann EM, Dom M, Koole R, Merkx MAW, Stoelinga PJW. Health related quality of life after mandibular resection for oral and oropharyngeal squamous cell carcinoma. Oral Oncol. 2005;41:687‐693. [DOI] [PubMed] [Google Scholar]
- 3. Van Cann EM, Oyen WJ, Koole R, Stoelinga PJ. Bone SPECT reduces the number of unnecessary mandibular resections in patients with squamous cell carcinoma. Oral Oncol. 2006;42:409‐414. [DOI] [PubMed] [Google Scholar]
- 4. Van Cann EM, Koole R, Oyen WJG, et al. Assessment of mandibular invasion of squamous cell carcinoma by various modes of imaging: constructing a diagnostic algorithm. Int J Oral Maxillofac Surg. 2008;37:535‐541. [DOI] [PubMed] [Google Scholar]
- 5. Hendrikx AWF, Maal T, Dieleman F, Van Cann EM, Merkx MAW. Cone‐beam CT in the assessment of mandibular invasion by oral squamous cell carcinoma: results of the preliminary study. Int J Oral Maxillofac Surg. 2010;39:436‐439. [DOI] [PubMed] [Google Scholar]
- 6. Kansy K, Mueller AA, Mücke T, et al. A worldwide comparison of the management of surgical treatment of advanced oral cancer. J Craniomaxillofac Surg. 2018;46:511‐520. [DOI] [PubMed] [Google Scholar]
- 7. Qiu Y, Lin L, Shi B, Zhu X. Does different mandibulectomy (marginal vs segmental) affect the prognosis in patients with oral squamous cell carcinoma? J Oral Maxillofac Surg. 2018;76:1117‐1122. [DOI] [PubMed] [Google Scholar]
- 8. De Vicente JC, Recio OR, Pendás SL, López‐Arranz JS. Oral squamous cell carcinoma of the mandibular region: a survival study. Head Neck. 2001;23:536‐543. [DOI] [PubMed] [Google Scholar]
- 9. Politi Massimo, Costa Fabio, Massim M. Review of segmental and marginal resection of the mandible in patients with oral cancer. Acta Otolaryngol. 2000;120:569‐579. [DOI] [PubMed] [Google Scholar]
- 10. Dubner S, Heller KS. Local control of squamous cell carcinoma following marginal and segmental mandibulectomy. Head Neck. 1993;15:29‐32. [DOI] [PubMed] [Google Scholar]
- 11. Patel RS, Dirven R, Clark JR, Swinson BD, Gao K, O'Brien CJ. The prognostic impact of extent of bone invasion and extent of bone resection in oral carcinoma. Laryngoscope. 2008;118:780‐785. [DOI] [PubMed] [Google Scholar]
- 12. Guerra MF, Campo FJ, Gias LN, Perez JS. Rim versus sagittal mandibulectomy for the treatment of squamous cell carcinoma: two types of mandibular preservation. Head Neck. 2003;25:982‐989. [DOI] [PubMed] [Google Scholar]
- 13. Muñoz Guerra MF, Naval Gías L, Campo FRg, Pérez JS. Marginal and segmental mandibulectomy in patients with oral cancer: a statistical analysis of 106 cases. J Oral Maxillofac Surg. 2003;61:1289‐1296. [DOI] [PubMed] [Google Scholar]
- 14. Woolgar JA, Scott J, Vaughan ED, Brown JS, West CR, Rogers S. Survival, metastasis and recurrence of oral cancer in relation to pathological features. Ann Roy Coll Surg. 1995;77:325‐331. [PMC free article] [PubMed] [Google Scholar]
- 15. Shen Q, Chen Y, Gokavarapu S, Cao W, Ji T. Primary intraosseous squamous cell carcinoma of the mandible: locoregional control and survival is significantly reduced if the tumour is more than 4 cm in size. Br J Oral Maxillofac Surg. 2018;56:48‐53. [DOI] [PubMed] [Google Scholar]
Associated Data
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Data Availability Statement
The datasets generated during and/or analyzed during the current study are not publicly available due to institutional restrictions but are available from the corresponding author on reasonable request.