Squamous cell carcinoma of the mandible – Patterns of metastasis and disease recurrence in dependence of localization and therapy☆
Introduction
Squamous cell carcinomas of the oral cavity (OSCC) form a major part within the group of head and neck squamous cell carcinomas (HNSCC) (Ferlay et al., 2010). Ranging among the eight most common malignant diseases worldwide, this entity is characterized by molecular and clinical heterogeneity (Alsahafi et al., 2019). The development of local disease recurrence and cervical and distant metastases has been shown to be the main prognostic factors in OSCC (Cooper et al., 2004; Akhtar et al., 2007; Pignon et al., 2009; D'Cruz et al., 2015). Surgical therapy is the established first-line standard of care and is combined with adjuvant radio- or radio-chemotherapy depending on tumor size and occurrence of metastases (Forastiere et al., 2001; Pignon et al., 2009; D'Cruz et al., 2015).
While in the past, OSCC were generally treated alike independent of their anatomic localization, lately evidence has grown showing that each subsite of the oral cavity exhibits distinct patterns of metastasis, disease recurrence and survival (Berger et al., 2015; Moratin et al., 2018, Moratin et al., 2019, Moratin et al., 2019).
Although several epidemiological studies presented clinical features of their investigated cohort, only a few have investigated the existence of site-specific relations between primary tumors, lymph node metastases and regional disease recurrence. Surgical tumor ablation in combination with elective neck dissection (ND) is regarded as the established first-line modality for the treatment of resectable OSCC. Nevertheless, radicalness and extent of the surgical procedures are a constant matter of debate. This applies especially for tumors located on or near the mandible. Here, surgical treatment options include either radical segmental resection or marginal resection. The surgeon often has to balance optimal oncological outcome and postoperative functionality and quality-of-life. Furthermore, there is no consistent standard in terms of uni- or bilateral neck dissection for patients with cN0 status. This may potentially lead to undertreatment in terms of insufficient primary and adjuvant therapy as e.g. postoperative radiation in most cases is being planned according to the pathological report. Even in pathologically confirmed cases of metastasis-free necks, bilateral ND improves adjuvant therapy as it is possible to reduce toxicity in these cases (Perkins et al., 2012; Spencer et al., 2014).
To avoid overtreatment with exaggerated surgical procedures and simultaneously achieve a maximum of oncological safety, there is an urgent need for preoperative risk assessment. This includes a rigorous validation of patients’ risk for the development of cervical metastases which has been shown to be influenced by the stage and localization of the primary tumor (Moratin et al., 2019, Moratin et al., 2019).
OSCCs located near the alveolar process of the mandible display an elevated risk of early bone infiltration. The specific rates of uni- or bilateral cervical metastases in dependence of T stage and sagittal localization of the primary tumor are crucial for therapy planning and the assessment of a patient's prognosis. Tumor removal including partial or segmental resection of the mandible is the established treatment (Brown et al., 2002; Rogers et al., 2004; Shaw et al., 2004; Mucke et al., 2011). Apart from achieving an optimal clinical outcome, preserving the patient's quality-of-life is a major goal in oncological therapy and mutilating surgical procedures should be limited to a minimum if possible. There are publications on clinical outcome depending on the extent of resection in patients with SCC located on the mandible (Brown et al., 2002; Wolff et al., 2004; Mucke et al., 2011). Nevertheless, the reported results and given recommendations are partly contradictory and there has not yet been a validation of different localizations within the mandible and their influence on metastasis and disease recurrence.
Therefore, the goal of this study was to investigate the incidence of regional metastases and patterns of disease recurrence in a cohort of patients with OSCC of the mandibular alveolar process in dependence of the sagittal tumor localization. Moreover, the prognostic impact of the extent of surgical therapy on clinical outcome was evaluated.
Section snippets
Data collection
The study was planned as a retrospective cohort study including patients with surgically treated squamous cell carcinoma of the mandible and was conducted in full accordance with ethical principles, including the World Medical Association Declaration of Helsinki (version 2002). Moreover, the protocol has been approved by the Ethics Committee of the Medical Faculty of the University of Heidelberg (Ethic vote: S-183/2015) and written informed consent was obtained from all patients. Inclusion
Patient cohort and therapy
120 patients met the inclusion criteria. 54 patients were female and 66 were male with a mean age of 67.6 ± 10.1 years. All patients received primary surgical treatment via tumor ablation including partial (n = 26, 21.7%) or complete segmental resection (94, 78.3%) of the mandible and uni- (n = 52, 43.3%) or bilateral (n = 68, 56.7%) neck dissection. 6 patients (5%) received a primary wound closure and 114 patients (95%) received a free flap reconstruction including 32 radial forearm flaps
Discussion
The purpose of this study was to evaluate different clinical and pathological factors affecting outcome in a cohort of patients with OSCCs located on the alveolar process of the mandible. Therefore, rates of metastases and disease recurrence in dependence of the localization of the primary tumors were investigated to facilitate therapy planning with regard to different strategies of surgical tumor resection and neck management. While surgical tumor removal whenever possible is the major
Conclusion
SCCs of the mandibular alveolar process display high rates of osseous infiltration and cervical metastases. The rate of contralateral cervical metastases is highest in tumors localized in the anterior part of the mandible and unlikely in tumors of the posterior part. Therefore, we recommend elective bilateral neck dissection in patients with OSCC of the anterior and intermediate part of the mandible irrespective of clinical tumor staging to allow for adequate risk assessment, planning of
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of Competing Interest
All authors declare that they have no conflict of interest.
Author Contributions
Julius Moratin: Conceptualization, Methodology, Data curation, Writing- Original draft preparation, Dominik Horn: Data curation, Writing- Reviewing and Editing, Karl Metzger: Software, Validation, Visualization, Investigation, Oliver Ristow: Methodology, Writing- Reviewing and Editing, Michael Engel: Methodology, Investigation, Writing- Reviewing and Editing, Jürgen Hoffmann: Supervision, Writing- Reviewing and Editing, Kolja Freier: Conceptualization, Methodology, Writing- Reviewing and
Acknowledgements
The study was supported by the Medical Faculty of University of Heidelberg.
References (28)
- et al.
Quality of life in oral cancer patients-effects of mandible resection and socio-cultural aspects
J Craniomaxillofac Surg
(2012) - et al.
Occurrence of cervical lymph node metastasis of maxillary squamous cell carcinoma - a monocentric study of 171 patients
J Craniomaxillofac Surg
(2015) - et al.
Factors that influence the method of mandibular resection in the management of oral squamous cell carcinoma
Br J Oral Maxillofac Surg
(2002) - et al.
Does medullary versus cortical invasion of the mandible affect prognosis in patients with oral squamous cell carcinoma?
J Oral Maxillofac Surg
(2017) - et al.
Squamous cell carcinoma of the maxilla: analysis of clinicopathological predictors for disease recurrence and metastatic behavior
J Craniomaxillofac Surg
(2018) - et al.
The occurrence of cervical metastases in squamous cell carcinoma of the tongue: is there a rationale for bilateral neck dissection in early-stage tumors?
J Craniomaxillofac Surg
(2019) - et al.
The prognostic significance of the lymph node ratio in oral cancer differs for anatomical subsites
Int J Oral Maxillofac Surg
(2020 May) - et al.
Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients
Radiother Oncol
(2009) - et al.
Does different mandibulectomy (marginal vs segmental) affect the prognosis in patients with oral squamous cell carcinoma?
J Oral Maxillofac Surg
(2018) - et al.
The importance of lymph node ratio for patients with mandibular infiltration of oral squamous cell carcinoma
J Craniomaxillofac Surg
(2018)
Mandible handling in the surgical treatment of oral squamous cell carcinoma: lessons from clinical results after marginal and segmental mandibulectomy
Oral Surg Oral Med Oral Pathol Oral Radiol
Influence of marginal and segmental mandibular resection on the survival rate in patients with squamous cell carcinoma of the inferior parts of the oral cavity
J Craniomaxillofac Surg
Neck involvement in early carcinoma of tongue. Is elective neck dissection warranted?
J Pak Med Assoc
Clinical update on head and neck cancer: molecular biology and ongoing challenges
Cell Death Dis
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