General treatment decision-making algorithm in oral cancer [D-Decision]
3.5.1 Curative Intent Treatment
The treatment algorithm for oral cavity cancer is summarized in Fig. 3.2.
Curative-intent treatment guidelines
22.214.171.124 Early-Stage Cancers with No Cervical Nodal Metastasis (T1, N0, M0)
Primary tumor: These cancers can be managed with a single modality treatment, either surgery or radiotherapy. The logic for this principle is that both the modalities can result in similar cure rates and more or less similar morbidity results. Surgery is preferred over radiotherapy as a single modality in sites where surgery is not morbid (cosmetically and functionally), lesions involving or close to bone; to prevent radionecrosis, young patients – possibility of a subsequent second primary and presence of submucous fibrosis (SMF). Radiotherapy is preferred over surgery as a single modality, where a severe impairment of function or cosmesis is likely with surgery, patient refuses surgery, or there is high risk for surgery . The preferred modality may also vary according to the patient preferences and across the treatment centers. However, general surgery is the preferred choice of treatment of oral cavity with the exception of commissure of mouth and selected buccal mucosal cancers .
Management of node-negative neck: Management of clinically and radiologically node neck is controversial. In general, the neck needs to be addressed if the chances of occult metastasis are more than 20 % . T1 buccal mucosa and T1T2 upper alveolus (gingiva) and T1T2 hard palate may qualify as having the chance of occult metastasis below 20 %. In advanced stages of these subsites and all stages of the remaining subsites, the neck needs to be addressed. However, there is a lack of good evidence defining the most appropriate treatment threshold. If primary is treated with surgery, the choice will be an elective neck dissection (END), and in cases where the primary is treated with radiotherapy, elective neck irradiation (ENI) is the choice. Also a cutoff tumor thickness of 4 mm  is also suggested as a threshold for addressing the neck. Perhaps the greatest limitation to use the 4 mm tumor thickness cutoff is the difficulty to obtain this information preoperatively, reliably, and in a cost-effective manner.
In a surgically treated case, the management options for dealing the clinically and radiologically negative neck include observation or elective neck dissection. Sentinel node biopsy is an upcoming strategy in between, but considering the evidence available, it may still have to be considered as an investigational tool.
The criteria for the levels of neck nodes that need to be cleared is well defined (ref). Elective selective neck dissection levels I–III are recommended for oral cavity primary. Level IV may be included in oral tongue tumors considering the possibility of isolated “skip metastasis” in level IV . But this is controversial [2, 17]. Advanced tumors of tongue, floor of mouth, and lip, especially those crossing the midline, will require contralateral selective neck dissection in addition.
In summary, since oral cancer has a high propensity for nodal metastasis, the neck needs to be addressed in majority of patients. Using a decision-tree algorithm, balancing morbidity and benefits, Weiss MH et al.  have determined that in cancer of oral cavity, if surgery is chosen as treatment option, elective neck dissection should be performed if the risk of occult metastasis is over 20 %. Though several clinic-pathologic factors have been evaluated to determine the tumors with high propensity for occult metastasis , depth of invasion of over 4 mm is determined as the single most important factor that correlates with occult nodal metastasis . However, it has been shown in a large prospective randomized trial that in patients with T1, T2 oral cavity cancers, elective neck dissection has significant survival advantage over wait-and-watch policy . Therefore, all but superficial tumors should be managed by elective neck dissection.
Based on the pattern of node metastasis, the type of neck dissection can be planned. In patients with all tumors other than tongue, they should be managed by selective neck dissection levels 1 to 3. For carcinoma of tongue, additional level 4 needs to be removed [2, 38, 43]. There were discussion about avoiding level 2b (supraspinal) group of nodes to minimize the risk of accessory nerve injury . The current status of sentinel node dissection is discussed in other chapter. As of now, there is no strong evidence for or against sentinel node biopsy in oral cancer with potential occult metastasis [20, 36, 42].
126.96.36.199 Oral Cancer with Clinically Positive Neck Disease (T2-T4a, N1/N >2, M0)
These tumors are managed with a combined modality approach. In oral cavity cancers, the preferred option would be surgery followed by adjuvant therapy, which can be either radiotherapy or chemoradiotherapy depending on the risk factors identified on the surgical specimen .
3.5.2 Treatment of Primary Tumor
Surgery involves the excision of the tumor with adequate three-dimensional margins, management of the neck, and appropriate reconstruction. Adequate resection is generally defined as the one that is done to obtain adequate clearance of the tumor all around. In oral cavity, at least 1 cm of the normal and palpable mucosa and 1 cm of the soft tissue in the third dimension is taken. This can be confirmed on frozen section and on specimen pathology. A clear margin is when there is 5 mm or more measurable distance between the tumor and the resection edge. A close margin is when there is between 1 and 5 mm, and a positive margin is when there is tumor at the cut edge or less than 5 mm distance between the tumor and the resection edge . But this may not be applicable universally across the oral subsites due to anatomical reasons . Oral tongue, being a muscular organ, this three-dimensional concept of margins beyond the tumor is easily applicable, but in other subsites, being closer to bone, a concept based on the anatomical layers  have to be applied. A normal tissue layer beyond the involved anatomical layer may be considered as adequate. This may involve the resection of a margin or segment of the mandible or maxillary bone as appropriate.
Management of mandible : When the tumor is close to or involving the mandible, a margin or a segment of the mandible needs to be resected.
Indications for marginal mandibulectomy:
Whenever tumor is close or abutting, the mandible has to achieve adequate margin.
Limited superficial bony erosion.
Limited periosteal invasion.
A minimum of 1 cm of inferior rim of the mandible needs to be retained.
Contraindications of marginal mandibulectomy:
Edentulous mandible in an elderly individual
Gross cortical and medullary involvement of the mandible
Gross paramandibular involvement of the tumor
Indications for segmental mandibulectomy:
Gross tumor invading the mandible
Gross paramandibular disease
Management of the skin: Skin involvement classifies as T4a disease. In situations where the tumor is either invading toward or involving the skin, resection of 1–2 cm of normal skin abutting the tumor is required .
188.8.131.52 Management of N-Positive Neck
The clinical and radiologic criteria of cervical nodes are well defined. These include the following.
Size criteria alone
>10 mm in short axis
Level I nodes >15 mm in short axis
Retropharyngeal nodes: >8 mm in short axis
It has been shown that size criteria alone can result in an error rate of 10–20 %. As more spherical nodes are likely to be metastatic, long-to-short axis ratio has been proposed. When the nodes have a ratio of >2 (elongated nodes), majority of the nodes will be benign. If the ratio is <2 (spherical nodes), it is likely to be metastatic .
Loss of fatty hilum
184.108.40.206 Management of Node-Positive Neck
A node-positive neck requires a comprehensive neck dissection including levels I–V (MRND). The non-lymphatic structures (spinal accessory nerve, internal jugular vein, and sternomastoid muscle) have to be preserved if not involved .
With the improved understanding of the pattern of cervical node metastasis, it has been even in cervical node positive patients, the tumor rarely metastasize to level 5. Moreover, level 5 metastasis is even rarer without tumor metastasis to level 4. Based on these findings in patients with N1 neck state, selective levels 1–3 for all oral cavity cancer is proven to be effective, with the exception that oral tongue cancer needs levels 1–4 dissection.
220.127.116.11 Management of the Contralateral Neck
Contralateral node-positive neck will require a comprehensive neck dissection. Contralateral node-negative neck needs to be addressed prophylactically with a selective neck dissection in large midline lesions or lesions crossing over the midline to involve the opposite side .
The conventional recommendation for any patients with clinically and radiologically node-positive disease is to undertake modified radical neck dissection clearing levels 1–5.
Principles of reconstruction are dealt separately in subsequent chapters.
18.104.22.168 Principles of Radiotherapy
Primary radiotherapy [24, 28, 33, 45]: Early-stage cancers of the oral cavity [lip, floor of the mouth, and retromandibular triangle] are curable by surgery or radiation therapy. Radical radiotherapy is used in treating T1 or T2 tumors with proliferative component, where the functional or cosmetic result is likely to be better, with similar chances of local control and survival.
Radiation therapy can be administered by external-beam radiation therapy (EBRT) or interstitial implantation alone. Small superficial tumors away from bone may be treated with interstitial brachytherapy alone, while for tumors more than 2 cm, usually both the modalities are combined. The addition of brachytherapy to EBRT has shown to improve the results compared to EBRT alone, but the time interval between them has to be as short as possible. Increasing the overall treatment time has shown to affect the treatment outcome adversely. When brachytherapy is used alone, the recommended dose is 66–70 Gy with LDR brachytherapy and 45–60 Gy with 3–6 Gy per fraction with HDR brachytherapy. When EBRT is used alone, the dose is 66–70 Gy in conventional fractionation over 6–7 weeks, or hypofractionated RT 5250 cGy in 15 fractions over 3 weeks. When the modalities are combined, 45–50 Gy is given initially with conventional fractionation to the primary site and nodal stations with EBRT. This is followed by brachytherapy boost to the primary tumor site with margins with a dose of 25–30 Gy with LDR or 21 Gy in 3 fractions with HDR brachytherapy.
3.5.3 Adjuvant Treatment
Postsurgical adjuvant treatment options depend on whether adverse features are present on pathology.
Indications of adjuvant radiotherapy [1, 34]:
Advanced T-stage (T3/T4)
Presence of lymphovascular invasion
Presence of perineural invasion
Positive surgical margins
Multiple lymph node involvement
Extracapsular nodal extension
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