Carcinoma Buccal Mucosa- Anatomy to Management

CA Buccal Mucosa from anatomy to management

1. Carcinoma Buccal Mucosa: Anatomy to management Dr. Ayush Garg

2. Anatomy Epidemiology Risk Factors Pre Malignant Lesions Clinical Features Pathology Diagnostic Work Up Staging Management Follow Up

3. ANATOMY The buccal mucosa includes the mucosal surfaces of the cheek and lips from the line of contact of the opposing lips to the pterygomandibular raphe posteriorly. This extends to the line of attachment of the mucosa of the upper and lower alveolar ridge superiorly and inferiorly.

4. The muscle of the cheek is the buccinator muscle. The buccal fat pad is superficial to the fascia covering the buccinator muscle and gives the cheeks a rounded contour. Branches of the maxillary and mandibular nerves (cranial nerves V2 and V3) provide sensory innervation to the skin, the cheek, and the mucous membranes lining the cheeks. The facial nerve (cranial nerve VII) provides motor innervation to the muscles of the cheeks and lips.

5. The lips and cheeks function together as an oral sphincter propelling food into the oral cavity. If the facial nerve is paralyzed, food tends to accumulate within the cheek along the affected side so that saliva and food dribble out of the corner of the mouth.

6. EPIDEMIOLOGY After carcinoma of the lip, oral tongue, floor of the mouth, and lower gum, carcinoma of the buccal mucosa is the fifth most common carcinoma of the oral cavity. It is the most common carcinoma of the oral cavity in India, Malaysia, and Taiwan. It usually occurs in the sixth and seventh decades of life, and is more prevalent in men than in women. Tobacco and betel nut chewing appear to play an important role in the cause of these tumors .

7. Carcinomas of the buccal mucosa often occur in association with pre-existing leukoplakia and tend to have multiple primary sites and recurrence. Excision of the oral leukoplakia may reduce the subsequent development of carcinoma. These tumors usually arise in the area adjacent to the lower molars along the occlusal line of the teeth.

8. RISK FACTORS

9. Premalignant lesions Leukoplakia - A chronic white mucosal macule which cannot be scraped off, cannot be given another specific diagnostic name, and does not disappear with removal of potential etiologic factors (excepting tobacco). 4-18% progress to invasive carcinoma

10. ERYTHROPLAKIA Erythroplakia is the clinical diagnostic term - A chronic red mucosal macule which cannot be given another specific diagnostic name and cannot be attributed to traumatic, vascular or inflammatory causes, i.e. it is a diagnosis of exclusion . Higher risk of cancer development ( approx 30%)

11. Oral Sub mucous fibrosis 4.5 – 7.5 % progress to oral cancer

12. Clinically, there are three distinct types: exophytic , ulcerative, and verrucous. The patient may present with pain or bleeding, trismus, or cervical lymphadenopathy. Posterior extension may result in involvement of the lingual or dental nerves, which may cause ear pain. Extension behind the pterygomandibular raphe into the pterygoid muscles or into the buccinator and masseter muscles may cause trismus.

13. Exophytic Ulcerative Verrucous

14. In advanced stages, the tumor may destroy the entire cheek and invade the adjacent bones and the neck. Infection is common and mastication becomes difficult. Death usually occurs as a result of poor nutrition and general debilitation

15. CLINICAL FEATURES Non Healing ulcer Pain Bleeding Dysphagia Referred pain to ear Hypersalivation Trismus

16. Trismus

17. Classification

18. ROUTES OF SPREAD Infiltrating lesions of the buccal mucosa can invade the buccinator muscle, extend to the buccal fat pad, and invade the subcutaneous tissue. Carcinomas of the buccal mucosa frequently spread by direct invasion into the gingivobuccal sulcus, the upper and lower alveolar ridges, the hard palate, the maxilla, and the mandible. Lymph node metastasis occurs in approximately 9% to 31% of the patients during the course of the disease.

19. The risk of subclinical disease is 16%. Distant metastases are rare, as patients often die of uncontrolled local disease before distant metastases are manifested clinically.

20. PATHOLOGY >90 % Squamous cell carcinomas Spectrum of diseases from benign lesions like leukoplakia, lichen planus, SMF to verrucous carcinoma to well differentiated squamous carcinoma Malignant Minor salivary gland tumors such as Adenoid cystic, Adenocarcinoma, Mucoepidermiod carcinoma (< 10%) are uncommon Malignant Melanoma, Lymphoma, Sarcoma occur rarely.

21. DIAGNOSTIC WORK UP History & Clinical examination , including head & neck examination Clinical staging Assessment of performance & nutritional status Investigations for histological diagnosis – Punch Biopsy

22. Investigations to determine the extent of the disease OPG/ Dental examination CT Scan / MRI for extent of disease USG for N0 neck in select cases

23. Routine Investigations CXR Routine blood counts Blood chemistry profile

24. STAGING T4a- Moderately advanced local disease. Tumor invades adjacent structures only (e.g., through cortical bone , [mandible or maxilla] into deep [extrinsic] muscle of tongue [ genioglossus , hyoglossus , palatoglossus , and styloglossus ], maxillary sinus , skin of face) T4b- Very advanced local disease. Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery

25. DISTANT METASTASIS (M) M0- No distant metastasis (no pathologic M0; use clinical M to complete stage group) M1- Distant metastasis GROUP T N M 0 Tis N0 M0 I T1 N0 M0 II T2 N0 M0 III T3 N0 M0 T1 N1 M0 T2 N1 M0 T3 N1 M0 IVA T4a N0 M0 T4a N1 M0 T1 N2 M0 T2 N2 M0 T3 N2 M0 T4a N2 M0 IVB Any T N3 M0 T4b Any N M0 IVC Any T Any N M1

26. PROGNOSTIC FACTORS

27. Intent of treatment Stage I – IV A : Curative Stage IV B-C : Palliative The aim of treatment: Cure Loco regional control Preservation of anatomy & function Reasonable cosmesis Quality of life

28. TREATMENT ALGORITHM

29. T1-2 N0 Excision of primary (preferred) ± unilateral or bilateral selective neck dissection. Neck treatment (dissection or RT) required for lesions >1.5–3 mm thick. For +margin only, re-excise if feasible. Post-op RT for pT3/T4, close margin, multiple nodes, PNI, and/or LVSI, or level IV–V nodes Post-op chemo-RT indicated for +margin, ECE Alternatively , EBRT ± brachytherapy. Salvage surgery for residual disease

30. T3 N0 Excision of primary and unilateral or bilateral selective neck dissection . Reconstruction as indicated. For + margin only , reexcise if feasible. Post-op RT for all; chemo-RT indicated for +margin, ECE

31. T4a or N1-3 Excision of primary and ipsilateral comprehensive neck dissection ± contralateral selective neck dissection, or bilateral neck dissection (for N2c). Reconstruction as indicated . For +margin only, reexcise if feasible. Post-op RT for pT3/T4, close margin, multiple nodes, PNI, and/or LVSI, or level IV–V nodes May consider post-op RT for N1 as only risk feature Post-op chemo-RT indicated for +margin, ECE

32. Unresectable Concomitant chemo-RT (preferred). Alternatively, induction chemotherapy followed by chemo-RT, or altered fractionation RT alone if unable to tolerate chemo. If primary has < CR, salvage surgery controversial. If residual neck mass by CT/MRI or PET at 6–12 weeks, post-RT neck dissection considered

33. VERRUCOUS CARCINOMA Perceived risk that the tumor may become more aggressive if it recurs after RT. Many tumors that recur after treatment are biologically more aggressive. Therefore, it is reasonable to treat these lesions with irradiation if surgery is not feasible. Wang reported a series of patients with verrucous carcinoma treated with RT; the results were comparable to those for patients treated for squamous cell carcinoma.

34. SURGERY Used as single modality in early disease (Stage I & II ) Combined with post operative adjuvant radiotherapy in advanced disease(Stage III & IV) Wide excision of tumor in all dimensions with adequate margins & appropriate neck dissection essential for locoregional control of disease

35. ADVANTAGES OF SURGERY Treatment time is shorter. The risk of immediate and late radiation sequel are avoided. Irradiation is reserved for recurrence, which may not be resectable. Pathological assessment, accurate staging. Disadvantage: functional & cosmetic impairment, increased morbidity when bilateral neck is addressed.

36. Modified neck dissection is sufficient treatment for the ipsilateral neck for patients with N1 without PNI. Radiation therapy is added for N1 with PNI/LVI N2,N3 stages, for control of contra lateral subclinical disease For invasion through the capsule of the node, For multiple positive nodes

37. NECK DISSECTION RND : superficial & deep cervical fascia with its enclosed LN (level I-V) is removed in continuity of SCM, omohyoid muscle, internal & external jugular veins, spinal accessory N & submandibular gland MND : is finding more acceptance & preference to RND in managing N0 neck because of severe morbidity related to RND such as, shoulder dysfunction, poor cosmesis, facial edema (level I-V LN)

38. SOHND : least morbid, provides most satisfactory sampling of the LN at the level I, II, III which are greatest risk Extended SOHND : level I-IV LN dissection

39. NCCN GUIDELINES FOR NECK TREATMENT

40. MANDIBULECTOMY Marginal mandibulectomy: partial-thickness (marginal) mandibular resection Segmental Mandibulectomy For small lesions with minimal bone invasion, a short section of mandible is removed in continuity with the tumor (e.g., removal of the mandible from the angle to the mental foramen). Hemimandibulectomy - Removal of the mandible symphysis to the condyle on one side. - Major cosmetic and functional loss - Reconstruction is performed with a composite osteomyocutaneous flap

41. Marginal mandibulectomy Segmental mandibulectomy

42. HPE REPORT Gross pathology 1. Morphology 2. Location & extent of the tumor / lesion 3. Tumor dimensions 4. Distance from various margins of excision 5. Nodal dissection

43. Microscopy 1. Histologic type 2. Grade 3. Extent of disease including depth of infiltration 4. Perineural invasion 5. Extracapsular Spread 6. Lymphovascular Invasion 7. Bone / Cartilage / Skin / Soft tissue involvement 8. Margins of excision, submucosal spread, In – situ changes 9. Nodal status – no. & size of nodes, perinodal extension & level of nodes 10. Status of cut margins

44. Miscellaneous features 1. In RND/ MND status of internal jugular vein 2. Presence of predisposing factors - leukoplakia, SMF 3. Dysplasia/ in situ elements

45. Unresectable Disease Primary disease Adequate surgical clearance is not achievable Extensive Infra Temporal Fossa involvement Extensive involvement of base skull Extensive soft tissue disease – skin edema / ulceration Nodal disease Clinically fixed nodes Infiltration of Internal / Common carotid artery Extensive infiltration of prevertebral muscles

46. IRRADIATION Better functional and cosmetic outcome Elective irradiation of the lymph nodes can be included with little added morbidity, whereas the surgeon must either observe the neck or proceed with an elective neck dissection (sometimes bilateral depending on the primary site), The surgical salvage of irradiation failure is probably more likely than the salvage of a surgical failure . The risk of postoperative complications is avoided

47. INDICATIONS OF POST OP RT Primary: Advanced primary – T3 or T4 Close or positive margins of excision Depth of invasion High grade tumor LVI & PNI Nodes: Bulky nodal disease N2/N3 Extra nodal extension Multiple level involvement

48. INDICATIONS OF POST OP CHEMO RT Extracapsular nodal involvement Positive Surgical Margin

49. RADIOTHERAPY BORDERS

50. T3 and T4 lesions Patients with significant tumor extension toward the midline are treated with parallel opposed fields weighted 3 : 2 toward the side of the lesion. The low neck is treated with an anterior field with a 6-MV X-Ray beam to 50 Gy in 25 fractions once daily

51. 3D CRT TARGET VOLUMES

52. RT DOSE Doses of 66-70  Gy in 1.8-2-Gy per fraction is given over 6.5-7 weeks Phase 1- 44 Gy is given over 4.5 weeks Phase 2-26 Gy is given over 2.5 weeks A LAN is often used, treated to either 50 Gy in 2-Gy fractions or 50.4 Gy in 1.8-Gy fractions.

53. ROLE OF IMRT

54. PASSPORT Trial: Numbers not enough to establish non- inferiority Conventional Radiotherapy IMRT 2 year PFS 80% 78% Estimated 2 year OS 76% 78%

55. IMRT TARGET VOLUMES GTV Gross tumor on imaging studies CTV High risk: GTV Intermediate risk: areas with high likelihood of nodal disease or tumor spread Low risk: elective nodal treatment PTV CTV plus 3–5 mm

56. DOSE RECOMMENDATION A total dose of 66–70 Gy in 30–33 fractions using simultaneous integrated boost (SIB) technique with 7–14 coplanar fields can be used according to the shape of PTV : High-risk PTV : 70 Gy to high-risk CTV Intermediate-risk PTV : 59.4 Gy Low-risk elective PTV : 50–54 Gy

57. PRESCRIPTION FOR HEAD & NECK IMRT 95 % prescription dose to cover 98% of high dose PTV Prescription dose to cover at least 91% of high dose PTV 95% dose to cover at least 95% of low risk PTV Avoid hotspots > 107% Parotid PRV Spine Mandible

58. BRACHYTHERAPY Accessible lesions Small (preferably < 3cm ) tumors Well defined borders Lesion away from bone Superficial lesions Tumors of the anterior two thirds of the buccal mucosa without involvement of gingiva are ideally suited for brachytherapy alone.

59. Interstitial implants with iridium wires or seeds in nylon ribbons can be considered for treatment of early, small lesions that have not invaded the buccogingival sulcus, the gingiva, or bone. Usually a minimum tumor dose of 60 to 70 Gy in 5 to 8 days is delivered through a single-plane or double-plane implant on the thickness of the lesion. The buccal mucosa tolerates high-dose RT with a low risk of late complications. Trismus may develop if the muscles of mastication receive high doses of irradiation.

60. CHEMOTHERAPY Cisplatin - Used in NACT (T4b and N3 cases) - Used in CTRT

61. FOLLOW UP

62. THANK YOU

63. Tumor factors Primary site Size Proximity to bone Status of cervical nodes Tumor pathology ( histological type, grade, & depth of invasion) Patient factors Age General medical conditions Tolerance of treatment Acceptance of expected sequelae of therapy Socioeconomic considerations

64. T1,T2 Tumors Primary Surgery : wide excision +/- marginal mandibulectomy Radiotherapy : Radical external RT/ Brachytherapy Nodes N0 : Observe or SOHD ( if cheek flap raised , USG suspicious, thick tumor or poor follow up expected) followed by Frozen section, if positive nodes, MND is required. N+ : MND/RND Post op RT as per guidelines

65. T3, T4 TUMORS Surgery + Post op RT or CT-RT Primary Surgery : Composite resection of the buccal mucosa with mandible or upper alveolus or overlying skin with reconstruction Nodes N0 : SOHD followed by FS, if positive nodes, MND required. N+ : MND/ RND