Decision making in Resection of Oral Cancer: How to go about it

Oral cancer is a global health problem with growing incidence and mortality rates. As highlighted by International Agency for Research on Cancer and World Health Organization on 2014, the early diagnosis of oral cancer reduces morbidity and mortality rates. The most accepted mode of initial definitive treatment for most oral cancers is surgical management. Various factors related to the primary Tumour and the patient affect choice of treatment. Primary site, location, size, proximity to bone, and depth of infiltration are factors which influence a particular surgical approach. Tumour’ s that approach or involve the mandible require specific understanding of the mechanism of bone involvement. Over time the role of surgery in primary squamous cell carcinomas in other sites in the head and neck has evolved with integration of multidisciplinary treatment approaches employing chemotherapy and radiotherapy either sequentially or concurrently. In this article, we throw light on the numerous component that influence the decision making of the surgeon before surgical resection in oral cancer.


Introduction
Oral cancer is the most common malignant disorder of the oral cavity, accounting for over 90% of all malignant neoplasms in this region. It accounts for majority of morbidity and mortality in individuals affected by head and neck cancer. They include a group of neoplasms affecting any region of the oral cavity, pharyngeal region, and salivary glands. It accounts for 2%-4% of all cancers worldwide and is ranked as the sixth leading cause of cancer mortality globally. About 30%-80% of the oral malignancies arise from premalignant disorders. Oral cancer has a multifactorial etiology. The various factors implicated in the etiopathogenesis of OSCC include smoking, chewing betel quid/tobacco, and alcohol intake separately or synergistically, viruses, genetic factors, environmental factors, and gene environment interactions [1,2].
For oral cancer, the treatment modalities can be classified according to the stage of the diseasea.
Stage I & II -Surgery b.
Stage II, III, IVA-Multimodality-including surgery along with adjuvant radiation therapy and/ or chemotherapy c.
Stage IVB &C-Beyond the scope of surgical intervention and only Radiation therapy or chemotherapy can be used [3].
Surgery is the most well-established mode of initial definitive treatment for most oral cancers, with the longest history of being the most accepted method of treatment for years over other treatment modalities. With the introduction of ionizing radiation, upon discovery of radium, radiation therapy (RT) became an important means of nonsurgical treatment of oral carcinoma. Although, in majority of patients with advanced stage of oral cancer, radiotherapy (RT) is administered as an adjuvant treatment modality in conjunction with suger. Chemotherapy in the management of oral carcinoma was considered palliative during the early years, though with the introduction of Cisplatinum, clinical trials of induction chemotherapy demonstrated that response to chemotherapy was observed in a significant number of patients. However, unlike other sites in the head and neck area, the response to induction chemotherapy did not translate into long term control of primary oral squamous cell carcinomas. Targeted therapies with EGFR inhibitors are an active area of investigation currently. Immunotherapy and gene therapy are also areas of research where further work needs to be done [2,3].

Factors Affecting Choice of Treatment
The factors that affect the choice of initial treatment are those related to the characteristics of the primary tumor, those related to the patient and those related to the treatment team. Thus, they are categorized as follows While deciding the optimal therapy for patients with oral cancer, one should consider these three sets of parameters in initial treatment planning. As the goal of treatment of cancer of the oral cavity is to eradicate the cancer, preserve or restore form and function, minimize the sequelae of treatment, and prevent any subsequent new primary cancers. To achieve these aims and objectives, the available treatment modalities include surgery, radiotherapy, chemotherapy, combined modality treatments and primary and secondary prevention strategies including lifestyle changes as well as chemoprevention.

Tumour factors
The tumour factors that affect the choice of initial treatment of oral cancer are primary site, size (T Stage), location (anterior versus posterior), proximity to bone (mandible or maxilla), status of cervical lymph nodes, previous treatment, and histology (type, grade and depth of invasion) [4]. The biological behaviour of primary cancers in the oral cavity is dependent upon the location of the disease, for example, cancers involving the hard palate and upper gingiva behave relatively indolently and lesser chances of regional lymph node metastases. Whereas, cancers involving the tongue, floor of the mouth have a high risk of regional lymph node metastases with an adverse impact on prognosis. The size of the primary tumour directly impacts the decision regarding choice of initial treatment. Small superficial primary tumours are easily accessible for surgical resection, while larger tumours require more extensive surgical approaches for exposure and excision. Also, larger size predisposes to higher risk of regional lymph node metastases mandating adjuvant therapy.
Neck dissection is an integral part of surgery in case of clinically palpable neck nodes although, the extent of level of cervical lymph nodes dissected will be dependent on the extent of nodal metastases and the location of palpable lymph nodes. The patterns of regional lymph node metastases from primary cancers of the oral cavity are well established and sequential progression of metastatic spread occurs from primary oral cancers [5]. The sentinel lymph nodes for oral cancer are located at levels 1, 2, and 3 in the neck with a relatively infrequent dissemination to level 4. Skip metastases to level 5 does not occur. Therefore, in planning elective dissection of regional lymph nodes for micro metastases, clearance of lymph nodes at level 5 is not necessary. On the other hand, when gross metastases are present in the anterior triangle of the neck, a comprehensive dissection of all five levels of lymph nodes is recommended [6,7].
The histology of the primary tumour is an important parameter which influences selection of initial treatment. Squamous carcinomas greatly predominate in the oral cavity and account for over ninety percent of all primary malignant neoplasms in the oral cavity. Patients with advanced stage disease, that is those presenting with spread to regional lymph nodes or with large primary tumours (T3 and T4), are candidates for consideration of combined modality treatment.

Patient factors
Many factors relative to patient characteristics play an important role in the selection of initial treatment for oral cancer. These include patient's age, general medical condition, and tolerance of treatment, occupation of the patient, acceptance and compliance by the patient, lifestyle (smoking and drinking) and other socioeconomic considerations. The ability of the patient to tolerate an optimal therapeutic program is equally important parameter which influences the choice of initial treatment. The patient's acceptance of and compliance with the proposed treatment also play a crucial role in designing an optimal treatment program for the tumour [3,7].

Physician factors
The factors related to the treatment delivery team are also important in making the selection of initial definitive treatment for oral cancer. Expertise in various disciplines including surgery, radiotherapy, chemotherapy, rehabilitation services, dental and prosthetic support, and psycho-social support are all crucial in bringing about a successful outcome of the therapeutic program. Management of cancer of the oral cavity is a multi-disciplinary team effort, and technical capabilities and support services from various disciplines are essential for a successful outcome [3,7].

Preoperative Assessment
The preoperative assessment forms an important link between the diagnostic phase and treatment phase of a disease. This assessment includes clinical, radiographic, and histopathological assessment. The radiographical assessment includes CT/MRI to assess bone & soft tissue invasion or PET-CT/ CT chest and ultrasound abdomen -to assess nodal involvement & distant metastasis. Radiographic imaging is essential in the preoperative work-up to assess primary tumour extent, regional disease, and distant disease, and to identify synchronous second primary tumours. Evaluation of the head and neck most often involve highresolution anatomic imaging. This usually is done via computed tomography (CT) with intravenous contrast material because this imaging modality is accurate and relatively inexpensive for the assessment of bone invasion as well as soft tissue extent of the primary tumour and regional nodal disease. Magnetic resonance Global Journal of Otolaryngology imaging (MRI) is superior for visualization of the soft tissue and hard palate and for evaluation of perineural invasion (PNI).
The histopathological assessment includes the use of intraoperative assessment/ frozen section to assess margin status. If the margins are at >1cm from the disease, then there is no need for re-resection. If the margins are <1cm, then re-resection is done. The final histopathology report post-operatively helps to assess nodal involvement, extracapsular spread, perineural invasion and final staging. All these parameters form an important criterion for deciding the adjuvant therapy if any needed [3,5,7].

Approach to Surgical Resection
The National Comprehensive Cancer Network (NCCN) recommends surgery for patients with early-stage tumours and surgery or definitive concurrent chemo radiotherapy for those with advanced-staged tumours. Surgery is often the first modality in sequential therapy because definitive high-dose radiation is associated with higher rates of Osteoradionecrosis. The goals of surgery are for complete resection of the primary tumour with negative margins and staging and treatment of regional lymphatics. Margin status is one of the most important variables associated with survival. There are various factors that affect the choice of a particular surgical approach for primary tumours of the oral cavity. These factors include the size of the primary tumour, its depth of infiltration, the site of the primary tumour (that is anterior versus posterior location) and proximity of the tumour to mandible or maxilla.
In addition to pre-operative clinical assessment of the primary tumour, examination under anaesthesia is often indicated to accurately delineate the extent of the tumour. The proximity of the tumour to the maxilla or mandible mandates the need for adequate clinical and radiographic assessment to rule out the possibility of bone invasion. The most employed imaging studies are a panoramic radiograph of the mandible (Orthopantomogram-OPG) [5]. Besides these, a more detailed assessment of mandible invasion can be accomplished with a CT scan and a dental scan. On the other hand, magnetic resonance imaging provides a detailed assessment of the extent of tumour infiltration in the soft tissue.
The most employed surgical approaches for resection of primary oral cancer are peroral, mandibulotomy, lower cheek flap approach, visor flap approach or upper cheek flap approach. The visor flap avoids a lower lip splitting incision and provides satisfactory exposure only for the anterior aspect of the oral cavity. It, however, produces numbness of the skin of the chin due to the necessity to divide both mental nerves. Similarly, a sublabial degloving approach avoids an upper lip splitting Weber-Ferguson incision for resection of tumours of the anterior part of the nasal cavity and the infrastructure of the maxilla [3,5].

Tumours involving buccal mucosa [3, 8-9]
The surgical approaches for primary tumours of buccal mucosa include following: i.
Peroral Approach-For accessible anterior lesions ii. Cheek

Tumours involving tongue and its base [3,8]
The surgical approaches for primary tumours of tongue mucosa include following: i.
Lesions in anterior tongue include a. Transoral with electrocautery resection b. Transoral with median glossotomy (Algorithm 2) If on CT assessment of bone -no bone invasion is seen, then the above two approaches without any bone sacrifice is enough. If on CT assessment of bone, it is found that bone is invaded then marginal/ segmental mandibulectomy is advised.

Global Journal of Otolaryngology
If on CT assessment of bone -no bone invasion is seen, then the above two approaches without any bone sacrifice is enough. If on CT assessment of bone, it is found that bone is invaded then marginal/ segmental mandibulectomy is advised. Treatment

Tumours involving floor of mouth [3,10,11]
The surgical approaches for primary tumours involving floor of mouth include following: Lesion that are small ie T1/T2 lesions which are 1cm away from mandible, Wide Local Excision (WLE) using the transoral approach is advised. The T3/T4 lesions i.e. lesions clinically larger than 2cm in greatest dimension can be operated according to the bone involvement status (Algorithm 3). For lesions without involvement of mandible bone, the standard treatment is extended resection with/ without partial glossectomy via the Transcervical pull through approach. For T3/T4 lesions involving the mandible bone, extended resection with/ without partial glossectomy with/without segmental mandibulectomy is the recommended plan of resection using the Lower lip splitting incision and lower cheek flap (Algorithm 4).

Tumour involving mandible
The tumours involving the mandible bone can be classified as follows based upon the involvement of mandibular cortex by the tumour. T1 lesions show no bone invasion, T2 lesions are the ones with alveolar bone invasion. While the T3 andT4 lesions are distinguished based on the invasion in relation to the level of mandibular canal (Figure 2). The surgical approaches for tumours involving the mandible include following: i.
Segmental resection/ mandibulectomy is advocated for tumours causing gross invasion of mandible along with Para mandibular soft tissue involvement via Lip splitting incision/ Lower cheek flap exposure/ Pull through approach. ii.
Marginal resection/ mandibulectomy is preferred for tumours of GB sulcus when mandible is in proximity to tumor but not involved or tumor of FOM abutting mandible. The approach used are Peroral approach/ Lip splitting incision (Figures 3 & 4).

Tumour involving maxilla & hard palate
The most used approaches for tumours of maxilla and hard palate are:

Management of Neck [3,13]
Neck dissection is the surgical procedure in which the fibrofatty contents of the neck are removed for the treatment of cervical lymphatic metastases (Figure 7). a.
Remove gross disease in patients with clinical evidence of nodal involvement (therapeutic neck dissection) b.
Remove occult metastases in patients whose tumor characteristics make one suspicious of occult cervical metastases

Radical neck dissection
Lymph nodes from level I-V, ipsilateral sternocleidomastoid muscle (SCM), internal jugular vein (IJV), and spinal accessory nerve (SAN) undergo removal. RND is indicated when N+ the neck for squamous cell carcinoma (SCC) where SAN involved and/ or extensive soft tissue disease with the invasion of SCM and IJV (Figure 8).

Modified radical neck dissection
Excision of same lymph node bearing regions as RND with preservation of one or more non-lymphatic structures (SAN, SCM, IJV) (Figure 9).

a.
Modified radical neck dissection type I (MRND-I): Lymph nodes from level I-V, ipsilateral sternocleidomastoid muscle, and internal jugular vein get removed, with preservation of the spinal accessory nerve. Indications for MRND-I is in N+ the neck for SCC where SAN is free of disease.

b.
Modified radical neck dissection type II (MRND-II): Removal of lymph nodes from level I-V and ipsilateral sternocleidomastoid muscle, with preservation of IJV and SAN. The N+ neck for SCC or thyroid cancer where IJV involved but SAN is free of disease.

c.
Modified radical neck dissection type II (MRND-III): Lymph nodes from level I-V undergo removal, with preservation of SCM, IJV, and SCM. MRND-III is indicated in metastatic differentiated thyroid carcinoma ( Figure 10). The severe comorbidities related to the removal of SCM, IJV, and SAN led to the numerous modifications of the procedure with selective removal of lymph nodes. They are: i.
Supraomohyoid neck dissection (SOHD): Lymph nodes removed are Levels I-III, with sparing of IJV, SCM, and SAN. SOHD is indicated in N0 neck for SCC of oral cavity and oropharynx (include level 4) and N0 neck malignant melanoma where primary site is anterior to ear (include parotidectomy for face and scalp). ii.
Extended supraomohyoid neck dissection (Ex SOHD): Removal of lymph nodes in levels I-IV, with sparing of IJV, SCM, and SAN. The procedure is indicated in N0 neck for SCC of the lateral tongue. iii.
Lateral neck dissection: Removal of lymph nodes from level II-IV with sparing of IJV, SCM, and SAN. Indications for this procedure are in N0 neck for SCC of larynx and hypopharynx.

iv.
Postero-lateral neck dissection: Removal of levels II-V, suboccipital, retro-auricular nodes with sparing of IJV, SCM, and SAN. Indications for this procedure is in N0 neck malignant melanoma where the primary site is posterior to ear.

v.
Modified lateral neck dissection: Removal of levels II to V lymph nodes with relative sparing of SCM, IJV, SAN, and submaxillary gland. This procedure has an indication of therapeutic neck dissection for thyroid cancer with lateral neck nodes (Table 1).

Conclusion
Thus, to conclude from this article we can understand that the entire process of decision making involves multiple steps and is directly/indirectly affected by many factors. These factors can be patient dependent or clinician dependent or disease dependent. The final treatment protocol decided for each patient is customized according to each individual and cannot be standardized for every patient. Therefore, a in depth understanding of the procedures and awareness about the latest techniques or advances in treatment modalities is a mandate for each professional.