Management of oral cancer

Transcription

1 Management of oral cancer Dr. Rafik Al Kowafi BDS, MSc, German board of Oral and Maxillofacial Surgery ( Berlin -Germany), Doctoral degree by LBMS Management of oral cancer Malignancies of the oral cavity may arise from a variety of tissues, such as salivary gland, muscle, and blood vessels, or may even present as metastases from distant sites. The most common malignancies are epidermoid carcinomas of the oral mucosa, which are the form of cancer that the dentist is in a position to discover first by doing thorough oral examinations. 2 1

2 Management of oral cancer 3 Management of oral cancer The seriousness of an oral malignancy can vary from the necessity for a simple excisional biopsy to composite jaw resection with neck dissection (i.e. removal of the lymph nodes and other visceral structures adjacent to lymph node channels in neck) to affect a cure. A thorough clinical examination and clinical staging should be undertaken before a treatment plan is formulated. 4 2

3 Physical Exam Oral Cancer Technique - Good lighting - Proper instruments - Systematic viewing Sequence - Remove denture(s), if present - Direct examination. - Palpation uni- & bimanual - Indirect mirror examination. - Flexible fiberoptic endoscopy, if required 5 Physical Exam Oral Cancer 6 3

4 Squamous Cell Carcinoma of the Tongue Ulcerative Exophytic 7 Palpation 8 4

5 Mouth With wooden tongue blade and a good light source. Inspect including the buccal folds and under the tougue - Note any ulcers, white patches (leukoplakia), or other lesions Palpate using a gloved finger the anterior structures and floor of the mouth Inspect the posterior oropharynx - Note any tonsillar enlargement, redness, or discharge

6 Neck Inspect for asymmetry, scars, visible thyroid, or other lesions. For thyroid: Note the size, symmetry, position of the lobes, and presence of any thyroid nodules (The normal thyroid is often not palpable). Laryngeal movement. Palpate to detect areas of tenderness, deformity, or masses. 11 Cervical Lymph Nodes 12 6

7 Lymph Node Levels 13 Indirect Laryngoscopy 14 7

8 Flexible Laryngoscope 15 Radiologic Exam Oral Cancer Mandible series / OPG/ CBCT bone invasion? Chest X-ray staging, second primary CA? CT surface and deep extent of primary tumor and nodal disease, chest evaluation MRI PET (Positron Emission Tomography) CT/PET increasingly utilized Not all of these done at once! 16 8

9 Radiologic Exam Oral Cancer 17 Radiologic Exam Oral Cancer CT-scan with contrast material 18 9

10 Radiologic Exam Oral Cancer PET 19 Biopsy Oral Cancer Incisional Excisional ( FNA ) Fine needle aspiration cytology 20 10

11 Tumor Staging T = Tumor size N = Lymph node involvement M = Distant metastases 21 Tumor Staging T X : Primary tumor cannot be assessed T 0 : No evidence of primary tumor T is : Carcinoma in situ T 1 : 2 cm or less in greatest dimension T 2 : > 2 cm but not more than 4 cm T 3 : > 4 cm in greatest dimension T4a: > Tumor invades adjacent structures (eg, through cortical bone, into deep[extrinsic] muscle of the tongue, maxillary sinus, skin of face) (resectable) T4b: > Tumor invades masticator space, pterygoid plates, or skull base or encases internal carotid artery (unresectable) 22 11

12 Tumor Staging NX: Regional lymph nodes cannot be assessed N 0 : No regional lymph node metastasis N 1 : Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension N 2 : Metastasis in a single ipsilateral lymph node, > 3 cm but not > 6 cm; or in multiple ipsilateral lymph nodes, none > 6 cm; or in bilateral or contralateral lymph nodes, none > 6 cm in greatest dimension 23 Tumor Staging N 2a : Metastasis in a single ipsilateral lymph node > 3 cm but not > 6 cm N 2b : Metastasis in multiple ipsilateral lymph nodes, none > 6 cm N 2c : Metastasis in bilateral or contralateral lymph nodes, none > 6 cm N 3 : Metastasis in a lymph node > 6 cm 24 12

13 Neck dissection- Staging of the neck 25 Tumor Staging M X : Presence of distant metastasis cannot be assessed M 0 : No distant metastasis M 1 : Distant metastasis 26 13

14 General Summary of TNM System T1 T2 T3 T4 NO N1 N2a N2b N2c N3 Stage Stage Stage Stage Stage Stage I III IVa IVa IVa IVb Stage Stage Stage Stage Stage Stage II III IVa IVa IVa IVb Stage Stage Stage Stage Stage Stage III III IVa IVa IVa IVb Stage Stage Stage Stage Stage Stage IVa IVa IVa IVa IVa IVb 27 Treatment modalities for oral malignancies Malignancies of the oral cavity are treated with: 1. Surgery. 2. Radiation. 3. Chemotherapy. 4. Combination of these modalities. Goals of therapy: 1. Tumor control 2. Functional preservation 3. Cosmetic 28 14

15 Treatment modalities for oral malignancies The treatment for any given case depends on several factors: 1. Histopathologic diagnosis. 2. Location of the tumor. 3. Presence and degree of metastasis. 4. Radiosensitivity or chemosensitivity of the tumor. 5. Age and general physical condition of the patient. 6. Experience of the treating clinicians. 7. The wishes of the patient. 29 Treatment modalities for oral malignancies If a lesion can be completely excised without mutilating the patient, this is the preferred modality. If spread to regional lymph nodes is suspected, radiation may be used before or after surgery to help eliminate small foci of malignant cells in the adjacent areas. If widespread systemic metastasis is detected or if a tumor, such as a lymphoma, is especially chemosensitive, chemotherapy is used with or without surgery and radiation

16 Treatment modalities for oral malignancies Currently malignancies are often treated in an institution where several specialists evaluate each case and discuss treatment regimens. These "tumor boards" include at least a surgeon, a chemotherapist, and a radiotherapist. Most head and neck tumor boards also include a general dentist, a maxillofacial prosthodontist, a nutritionist, a speech pathologist, and a sociologist or psychiatrist Surgical Therapy of oral Cancer Pathology: Squamous Cell Carcinoma (SSC): >90% of oral cancers Verrucous Carcinoma: variant of SSC, broad based, warty growth most common site is the buccal mucosa, lateral growth, rare metastasis and deep invasion Basal Cell Carcinoma: more common on the upper lip Other Types: Lymphoma, Kaposi s Sarcoma, Salivary Gland, malignancies, Melanoma NOTE: Necrotizing Sialometaplasia and Granular Cell Tumors may be mistaken for squamous cell carcinoma in the oral cavity due to similar histology (pseudoepitheliomatous hyperplasia) 32 16

17 1- Surgical Therapy of oral Cancer Long-term survival and functional results of treatment depend on the stage of the tumor, histology, and treatment plan. The treatment plan is developed at pretreatment conferences (tumor boards) by multidisciplinary consultants and subsequent patient/family concurrence. Additional important outcome factors include the patient s nutritional status, general health, tobacco use, alcohol intake, and anticipated compliance with the rigors of therapy Surgical Therapy of oral Cancer The surgical operation aims to remove the carcinoma, with a 1-2 cm margin of normal tissue beyond the clinical edge of the tumour where possible. In addition to the treatment of the primary tumor, the cervical lymphatics commonly require treatment (Neck dissection). The clinically negative neck (no evidence of lymph node involvement) may be treated electively by radiation or modified neck dissection 34 17

18 1- Surgical Therapy of oral Cancer Early Oral Cancer (T1 T2) Single-Modality Therapy: excision of primary tumor with primary reconstruction, may consider primary radiation. N0 Neck: elective ipsilateral or bilateral (midline or oral tongue cancer) selective neck dissection (supraomohyoid) versus external beam therapy (early stage hard palate or lower lip do not require elective neck dissections because of lower rate of occult metastasis); if surgical specimen is positive for tumor may consider observation, completion of a comprehensive neck dissection, or radiation therapy to neck. N1 3 Neck: radical neck dissection for clinical nodes; parotid nodes require a superficial parotidectomy Surgical Therapy of oral Cancer A, Superficial squamous cell carcinoma of the right oral tongue. The tumor measured 3 cm and had minimal induration, and there were no palpable lymph nodes. B, Five weeks after excision, the patient was completely healed, with no pain or impediments in tongue function. The patient was followed for more than 5 years without any evidence of recurrence

19 1- Surgical Therapy of oral Cancer Advanced Oral Cancer (T3 T4) Single-Modality Therapy: excision of primary tumor with primary reconstruction versus primary radiation for non-operable candidates. N0 Neck: elective ipsilateral or bilateral (midline or oral tongue cancer) selective neck dissection (supraomohyoid) versus radiotherapy; if surgical specimen is positive for tumor may consider observation, completion of a comprehensive neck dissection, or radiation therapy to neck N1 3 Neck: radical neck dissection for clinical nodes; parotid nodes require a superficial parotidectomy. Adjuvant Therapy: postoperative radiation therapy may be considered for positive margins; multiple positive neck nodes or extracapsular extension; perineural or intravascular invasion; or bone, cartilage, or soft tissue invasion. chemotherapy indicated for palliation or may be considered for adjuvant treatment for advanced disease Surgical Therapy of oral Cancer Lip Cancer Single-Modality Therapy: excision of primary tumor with primary reconstruction versus primary radiation therapy for small tumors or non-operable candidates (must also consider functional and cosmetic outcomes). Adjuvant Therapy: postoperative radiation therapy may be considered for advanced stages (T3 4, N2 3), positive margins, multiple positive neck nodes, perineural or intravascular invasion, or extracapsular extension. N0 Neck: elective ipsilateral or bilateral (for lower lip midline disease) selective neck dissection (supraomohyoid) versus radiotherapy for advanced diseases (T3 T4); if surgical specimen is positive for tumor may consider observation, completion of a comprehensive neck dissection, or radiation therapy to neck. N1 3 Neck: radical neck dissection for clinical nodes; parotid nodes require a superficial parotidectomy. chemotherapy may be considered for palliation or adjuvant treatment for advanced disease

20 1- Surgical Therapy of oral Cancer Surgical approaches: 1. Transoral excision. Premalignant lesions and small, superficial tumors of the anterior floor of mouth, alveolus, and tongue may be resected through the open mouth. 39 Transoral excision of a tongue tumor ( A ) preexcision. ( B ) postexcision

21 1- Surgical Therapy of oral Cancer 2. Cheek flaps. Tumors of the posterior oral cavity are not easily accessible transorally, and a cheek flap may give more adequate exposure in appropriate cases. I. Upper cheek flap (Weber Fergusson flap): is raised using a median upper lip split and carrying the incision around the nose with the corresponding mucosal incision in the upper gingivobuccal sulcus. II. Lower cheek flap: requires a midline lip split that continues over the chin into the neck. The flap is raised subplatysmally, but great care must be exercised not to strip the periosteum off the mandible. Accurate replacement of a cheek flap is facilitated by leaving a substantial mucosal cuff on the alveolar side Surgical Therapy of oral Cancer III. Midfacial degloving flap: through bilateral gingivobuccal incisions is preferable in appropriate cases as this avoids midfacial scars. IV. A visor flap can give access to both sides of the neck and avoids splitting the lip, but adequate mobilization results in division of both mental nerves with post-operative anesthesia of the lip

22 Surgical approaches Intraoral degloving Weber Fergusson (upper cheek flap) 43 Surgical approaches a. Transoral. b. Mandibulotomy. c. Lower check flap. d. Visor flap. e. Upper check flap

23 1- Surgical Therapy of oral Cancer 3. Mandibulotomy. Larger tumors of the lateral border of the tongue or those involving or extending onto the floor of the mouth require a lip-splitting mandibulotomy approach. Similarly, adequate surgical exposure of tumors located in the posterior oral cavity may be obtained using a mandibulotomy. 45 Mandibulotomy 46 23

24 Mandibulotomy Surgical Therapy of oral Cancer Management of the Mandible: Mechanism of invasion of the mandible. Tumors of the floor of the mouth, the ventral surface of the tongue, and the gingivobuccal sulcus spread along the mucosa and submucosal to the adjacent gingiva

25 1- Surgical Therapy of oral Cancer 1. Marginal resection of the mandible (rim resection): The understanding of tumor invasion into mandible enables the use of marginal resection of bone based on the observation that the cortical part of the bone containing the mandibular canal lies inferior to the dental roots, remains relatively uninvolved in early stage disease, and can be safely spared. Indications: a) Primary tumor against the mandible abutting b) Minimal involvement of the alveolar process c) Minimal cortical erosion Surgical Therapy of oral Cancer 2. Segmental mandibulectomy: (Composite resection) Indications: a) Invasion of the mandibular canal and inferior alveolar nerve b) Gross invasion of the mandible c) Primary mandibular osseous tumor d) Metastatic tumor to the mandible 50 25

26 1- Surgical Therapy of oral Cancer A, deeply infiltrating squamous cell carcinoma involving the entire anterior floor of the mouth and mandible. B, Treatment involved composite resection followed by radiation. Reconstruction was critical to function, appearance, and quality of life. 51 Neck Dissection ( A ) Incidence of occult lymph node involvement in the clinically node negative patient with alveolar ridge cancer. ( B ) Incidence of lymph node metastasis in the clinically node-positive patient with alveolar ridge cancer

27 Lymph node levels/nodal regions Level I: Submental and submandibular triangles. Levels II, III, IV: nodes associated with IJV within fibroadipose tissue (posterior border of SCM and lateral border of sternohyoid). Level V: Posterior triangle of neck Boundaries - posterior border of SCM, clavicle, and anterior border of trapezius. Level VI: Anterior compartment structures (hyoid, suprasternal notch, medial border of carotid sheath). 53 Lymph node levels/nodal regions 54 27

28 Classification of Neck Dissections Based on 4 concepts 1) RND (Radical Neck Dissection) is the standard basic procedure for cervical lymphadenectomy against which all other modifications are compared. 2) Modifications of the RND which include preservation of any non-lymphatic structures are referred to as modified radical neck dissection (MRND). 3) Any neck dissection that preserves one or more groups or levels of lymph nodes is referred to as a selective neck dissection (SND) 4) An extended neck dissection refers to the removal of additional lymph node groups or non-lymphatic structures relative to the RND. 55 Classification of Neck Dissections 1) Radical neck dissection (RND) 2) Modified radical neck dissection (MRND) 3) Selective neck dissection (SND) Supra-omohyoid type Lateral type Posterolateral type Anterior compartment type 4) Extended radical neck dissection 56 28

29 Definition: Radical Neck Dissection Removal of all lymph nodes in Levels I-V including spinal accessory nerve (SAN), SCM, and IJV. Indications: Extensive cervical involvement or lymph nodes with gross extracapsular spread and invasion into the SAN, IJV, or SCM 57 Modified Radical Neck Dissection Definition: Excision of same lymph node bearing regions as RND with preservation of one or more non-lymphatic structures (SAN, SCM, IJV) Indications: Clinically obvious lymph node metastases SAN not involved by tumor Intraoperative decision 58 29

30 Selective Neck Dissection Definition: Cervical lymphadenectomy with preservation of one or more lymph node groups. Also known as an selective neck dissection. Rate of occult metastasis in clinically negative neck 20-30% Need for post-op XRT (Radiotherapy). Four common subtypes: 1. Supraomohyoid neck dissection (SOHND) 2. Posterolateral neck dissection 3. Lateral neck dissection 4. Anterior neck dissection Indications: Primary lesion with 20% or greater risk of occult metastasis 59 SND: Supraomohyoid type Most commonly performed SND Definition: En bloc removal of cervical lymph node groups I-III. Posterior limit is the cervical plexus and posterior border of the SCM. Inferior limit is the omohyoid muscle overlying IJV. Indications: Oral cavity carcinoma with N0 neck, Subsites - Lips, buccal mucosa, upper and lower alveolar ridges, retromolar trigone, hard palate, and anterior 2/3s of the tongue. SOHND + parotidectomy Melanoma and cutaneous SCCA of the cheek 60 30

31 SND: Supraomohyoid type

32 2- Radiotherapy Radiotherapy (RT) is an extremely effective treatment for head and neck cancer, as a primary modality and as an adjuvant treatment following surgery. In early-stage disease, single modality radical RT can cure >90% of cancers in some tumor subsites (e.g., larynx). In more advanced-stage diseases, RT is usually used in combination with chemotherapy (e.g. cisplatin), either as radical chemoradiotherapy or in an adjunctive fashion after surgery. Most cancers of the head and neck are squamous cell carcinomas (HNSCC) and are generally considered to be radiosensitive lesions. There is a well-established relationship between the radiation dose delivered to the tumor and the probability of tumor control Radiotherapy RT can be delivered via external beam and/or brachytherapy. For stage III and IV HNSCC, surgery and postoperative chemoradiation are effective. Lesions with high probabilities of cure (>70%) should ideally be treated with a single therapeutic modality (either surgical or nonsurgical). The increased morbidity of combined surgical and nonsurgical treatment is unjustified, especially when not associated with a significantly improved control rate. However, there are circumstances in which RT and surgery are used as part ofa planned treatment program

33 2- Radiotherapy How RT works? Ionizing radiation may be delivered in the form of external beams of x-rays or gamma rays, external beams of electrons or particles (neutrons or protons), or internally implanted sources of beta or gamma rays. Radiation kills cells by primary and secondary interactions with the cells making up the tissues. In general, the photons of x-rays or gamma rays dislodge electrons from the atoms of the tissue. These charged particles cause ionization along their tracks, which results in chemical changes in the water in the cell and in the critical macromolecules of the cell, primarily the deoxyribonucleic acid (DNA). The major site of action of ionizing radiation on mammalian cells is in the nucleus, where it causes breakage of chromosomes and disruptions or misrepair of the DNA molecule. In some types of cells, such as mature lymphocytes and tumor cells, radiation has a direct effect on the function of the nucleus and causes programmed cell death (apoptosis). In most cases, the damage is to the DNA and chromosomes, and cell death results after several divisions. It should be noted that cells need not actually die to be mitotically dead. For instance, they may divide once or twice but then remain in a postmitotic state and form giant cells that are no longer capable of causing tissue or tumor regeneration. Rad (Radiation Absorbed Dose): amount of energy deposited by ionizing radiation per gram of tissue (1 Gy = 100 rads) Radiotherapy Types of RT: 1. Preoperative Radiation Therapy: Preoperative RT is infrequently used and should not be considered to be a standard of care. It can be indicated in: (1) fixed, inoperable neck nodes. (2) in situations where the initiation of postoperative RT is likely to be delayed by more than 6 8 weeks due to the need for extensive surgical reconstruction. 2. Postoperative Radiation Therapy: Postoperative RT is usually considered when the risk of recurrence above the clavicles exceeds 20%. The operative procedure should be one stage and should ideally allow irradiation to start no later than 6 weeks after surgery

34 2- Radiotherapy Indications for Postoperative Radiation Therapy 1. Positive margins at the primary tumor resection site. 2. Less than 5 mm safe margins. 3. Extracapsular spread of involved lymph nodes. 4. Two or more involved cervical lymph nodes. 5. Invasion of the soft tissues of the neck. 6. Lymphovascular and perineural invasion. Radiation therapy techniques: 1. Brachytherapy. 2. Conventional Radiation Therapy. 3. Three-Dimensional Conformal Treatment Planning. 4. Intensity Modulated Radiotherapy Radiotherapy 1- Brachytherapy: Brachytherapy describes the situation in which Radioactive sources are brought close to the tumor mass (or even implanted within it) to deliver a highly localized radiation dose

35 2- Radiotherapy 2- Conventional Radiation Therapy: Conventional RT involved treatment planning by fluoroscopic X-ray screening and treatment delivery by one to four regular square or rectangular fields. Blocks of lead (or of a dense alloy called Cerrobend) were positioned by hand such that they shielded parts of the radiation field encompassing normal structures Radiotherapy 3- Three-Dimensional Conformal Treatment Planning (3-DCRT): CT-scan is taken with the patient immobilized in the RT treatment position. Data from these scans provide the radiation oncologist with precise anatomical and electron density data on tumor and normal tissues. This technique is more time-consuming than conventional RT and requires specialist technical support, but it offers the opportunity of achieving clinically important improvements in tumor control and reductions in normal tissue complication

36 3- Chemotherapy 3- Intensity Modulated Radiotherapy. This treatment technique permits the generation of concavities in the isodoses within tissues such that normal structures can be spared from excessive radiation doses. IMRT uses sophisticated computer software and hardware to vary the shape and intensity of radiation delivered to different parts of the treatment volume. 71 Radiation doses and treatment delivery A conventional course of RT for HNSCC is delivered over a 6 7-weeks course with small fractions of radiotherapy delivered 5 days a week. A standard schedule (e.g. in the U.K) is 70 Gray (Gy) delivered in 35 fractions over 7 weeks. RT is delivered in multiple small fractions to allow recovery of normal tissues between doses and thus facilitate the delivery of a larger total radiation dose to the tumor

37 Palliative Radiotherapy RT can also be used with palliative intent in patients for whom a curative treatment option does not exist. Indications: 1. As initial treatment for locally advanced tumors in patients with very poor health status who will not be able to tolerate radical treatment. 2. For short-course treatment of local disease in metastatic (M1) disease at the initial presentation. patients with 3. For symptom relief (pain, bleeding, airway compromise) in patients with locally recurrent. 4. For symptom relief of distant metastatic disease (e.g., bone pain, spinal cord compression). Palliative RT is usually delivered as a short course of treatment that can vary from a single fraction to 10 doses of RT over a 2-week period. 73 Case Presentations /Radiation Planning Case Study: 39 yr old male with 25 yr history of cigarette use (2 packs per day) and intermittent history of marijuana use. He complains of 2 month history of biting the inside of his right cheek Physical exam shows bilateral leukoplakia on buccal mucosal and no palpable lymphadenopathy 74 37

38 Case Presentations /Radiation Planning OMF surgeon notes small area of erythroplakia on left buccal mucosa Bilateral biopsies reveal moderate dysplasia on the right buccal mucosa and moderately differentiated squamous cell carcinoma on the left. Multidisciplinary tumor board recommends definitive radiation therapy for a 1 cm tumor (T1N0) on the left buccal mucosa

39 Case Presentations /Radiation Planning Patient received definitive, radiation therapy to the primary tumor and ipsilateral levels I, II, and III LN stations. Primary tumor had a complete response by the end of 72 Gy of radiation. Patient only had mild xerostomia since contralateral salivary glands were spared. 77 Radiation- Induced side effects 1- Acute Effects 1. Mucositis. 2. Oral candidiasis. 3. Tongue sensitivity. 4. Decreased taste. 5. Fatigue. 6. Xerostomia. 7. Dysphagia. 8. Weight loss. 9. Hair loss

40 Radiation- Induced side effects Dental Recommendations for Acute Effects: 1. No dental prostheses should be worn during radiation once irritation, mucositis, or ulceration develops. 2. Meticulous oral hygiene: Frequent brushing (after meals, night) Daily flossing Daily fluoride gel applications with custom carriers Chlorhexidine mouthwash. Disadvantages (more discomfort, taste alteration, teeth staining). Baking soda and salt rinses are most beneficial. BMX ((Benadryl-Maalox- Xylocaine) mouth rinse and liquid pain medicines are helpful 79 Radiation- Induced side effects 2- Potential late effects: 1. Permanent xerostomia. 2. Change in taste 3. Dental caries (Why?) 4. Soft tissue necrosis (Ulcers) 5. Bone necrosis (osteoradionecrosis) 6. Radiation-induced tumors 80 40

41 Radiation- Induced side effects Dental recommendations for Late effects: Frequent, professional dental care may prevent demineralization of teeth If enamel breakdown, calcium phosphate remineralizing gel is used. Ideally a healing time of at least 3 weeks between dental procedures such as extractions and the initiation of radiotherapy significantly decreases the chance of bone necrosis. Teeth extractions should be avoided if possible especially in regions of bone receiving over 50 Gy. If teeth extractions are necessary, conservative surgery, antibiotic coverage, and possibly hyperbaric O 2 should be considered. Removable prosthesis are constructed after mucosa is healed. 81 Radiation- Induced side effects Soft tissue necrosis Relatively common Typically small, and self-limited Must rule out recurrent cancer Management: Observation Antibiotics (tetracycline) Comfort agents: viscous lidocaine or BMX Hyperbaric O 2 is used for larger lesions or bone necrosis 82 41

42 Radiation- Induced side effects Osteoradionecrosis Dentures discontinued, or modified to decrease trauma Usually no cases of bone necrosis are reported if dose bone <65 Gy Risk increases greatly for dose bone >75 Gy Management is conservative (analgesics, antibiotics, good hygiene) Hyperbaric O 2 is sometimes helpful. Surgery is used as a last resort for treatment of soft tissue or bone necrosis. 83 Radiation- Induced side effects Xerostomia Dependent on dose (tolerance ~ 32 Gy) Dependent on volume of salivary gland tissue irradiated (mild if can spare 1 parotid). Treatment options: Pilocarpine post-radiation, amifostine concurrent with radiation for prevention of xerostomia. Artificial saliva Muscles of Mastication If included in radiation field, fibrosis may occur. Patient should exercise muscles to prevent trismus (open/close, open against pressure)

43 3- Chemotherapy Chemotherapy: The treatment of cancer using specific chemical agents or drugs that are destructive to malignant cells and tissues. Traditional chemotherapeutic agents act by killing cells that divide rapidly, one of the main properties of most cancer cells. This means that chemotherapy also harms cells that divide rapidly under normal circumstances: cells in the bone marrow, digestive tract, and hair follicles Chemotherapy This results in the most common side-effects of chemotherapy: myelosuppression (decreased production of blood cells, hence also immunosuppression), mucositis (inflammation of the lining of the digestive tract), and alopecia (hair loss). Some newer anticancer drugs target proteins that are abnormally expressed in cancer cells and that are essential for their growth. Such treatments are often referred to as targeted therapy, and are often used alongside traditional chemotherapeutic agents in antineoplastic treatment regimens

44 3- Chemotherapy Two Broad Classes of Chemotherapy Drugs: 1. Cytotoxic agents: Cisplatin causes DNA damage 5-Fluourouracil blocks enzymes necessary for RNA and DNA synthesis Docetaxel inhibits microtubule formation 2. Targeted therapies: Erlotinib small molecule inhibitor the EGFR (epidermal growth factor receptor) tyrosine kinase Cetuximab antibody that binds to EGFR 87 Common Chemotherapy Agents and Combinations in Head and Neck Cancer Cisplatin Mechanism of Action: heavy metal that acts as an alkylating agent that covalently binds DNA and RNA Common Side Effects: nausea, nephrotoxicity, peripheral neuropathy, ototoxicity, electrolyte disturbances, anorexia Indications: best singleagent against squamous cell carcinoma of the head and neck in recurrent disease; common combination agent for neoadjuvant, adjuvant, and concomitant chemotherapy of the head and neck; radiation sensitizer. Carboplatin Mechanism of Action: similar to cisplatin (less reactive). Common Side Effects: better tolerated than cisplatin (less nephrotoxicity, nausea, neurotoxicity, and ototoxicity) Indications: not been fully investigated in head and neck cancer, often used in combination with taxol 88 44

45 Common Chemotherapy Agents and Combinations in Head and Neck Cancer 5-Fluorouracil (5-FU) Mechanism of Action: antimetabolite that binds to thymidilate synthetase blocking the conversion of uridine to thymidine preventing DNA synthesis in S-phase. Common Side Effects: anorexia and nausea, mucositis, diarrhea, alopecia, myelosuppression, cardiac toxicity. Indications: similar to cisplatin (cisplatin and 5-FU is the most studied combination chemotherapy regimen in head and neck cancer) 89 Common Chemotherapy Agents and Combinations in Head and Neck Cancer Methotrexate Mechanism of Action: antimetabolite that binds to dihydrofolate reductase preventing DNA synthesis in S-phase Common Side Effects: bone marrow suppression, gastrointestinal disturbances, mucositis, alopecia, dermatitis, nephrotoxicity, teratogenicity, interstitial pneumonitis Indications: standard palliative therapy for recurrent or metastatic disease Taxanes (Paclitaxel and Docetaxel) Mechanism of Action: prevent normal microtubular reorganization Common Side Effects: neutropenia, alopecia, mucositis Indications: currently being investigated for recurrent disease and as a potential radiation sensitizer

46 There is a wide variation in sensitivity of various cancers to chemotherapy: High Intermediate Low Lymphoma Breast Head and neck Leukemia Colon Prostate Small Cell Lung cancer Testicular cancer Non-small cell lung cancer Gastric Pancreatic 91 Chemotherapy Administration and Dosing Doses are individualized based upon a patient s BSA (body surface area). Drugs are given in cycles, usually at 3-4 week intervals Chemotherapy is often combined with surgery and/or radiation 92 46

47 Modes of Chemotherapy Primary Chemotherapy - chemotherapy is used as the sole anti-cancer treatment in a highly sensitive tumor types Example CHOP for Non-Hodgkins lymphoma Adjuvant Chemotherapy treatment is given after surgery to eliminate microscopic residual disease Example Adriamycin, cyclophosphamide for breast cancer Neoadjuvant chemotherapy treatment is give before surgery to shrink tumor and increase chance of successful resection Example Adriamycin, ifosfamide for osteosarcoma Concurrent chemotherapy treatment is given simultaneous to radiation to increase sensitivity of cancer cells to radiation Example Cisplatin, 5-fluourouracil, XRT for head and neck tumors 93 Chemotherapy toxicity: Hematologicanemia, neutropenia, thrombocytopenia, immunosuppression Skin/Mucosascaling, mucositis, alopecia Cardiacdecreased myocardial contractility, arrhythmias Renal/GUacute tubular necrosis, chronic renal insufficiency, hemorrhagic cystitis, sterility Neurologichearing loss, peripheral neuropathy GIT- Nausea/vomiting, diarrhea Osteonecrosis 94 47

48 Oral Toxicity Mucositis Xerostomia Dental pain Osteonecrosis Oral mucosal infections Dental pulp/periapical infections Peridontal infection Mucosal hemorrhage 95 Cisplatin/5-FU Regimen for Head and Neck Cancer 1. Prehydrate IV NS 2. Induce diuresis Lasix, mannitol 3. Antiemetic Zofran, Decadron 4. Cisplatin over 1 hour IV (based on height and weight) 5. Posthydrate with electrolytes 6. 5-FU continuous IV infusion 24 hrs x 5 days (dose based on height and weight) 7. Daily antiemetics, IVF 8. Repeat at 3 or 4 week intervals 9. Concurrent radiotherapy 96 48

49 Summary Two broad classes of chemotherapy are cytotoxic drugs and targeted drugs Chemotherapy is often used as an adjunct to surgery and/or radiation therapy (adjuvant, neoadjuvant, concurrent) Chemotherapy toxicities can be severe, and are generally specific to a drug s mechanism of action. 97 Summary Standard therapy for resectable disease remains surgery followed by radiotherapy, if indicated. To date, induction chemotherapy followed by surgery has not shown a survival benefit in oral cavity cancer. Adding chemotherapy following surgery and radiation has been shown to decrease the incidence of distant metastases, but this has not been associated with improved survival

50 Chemoprevention An additional area of intensive research is development of chemoprevention agents, which are defined as agents that reverse or suppress premalignant carcinogenic progression to invasive malignancy. The role of such agents would be twofold: (1) To treat premalignant lesions to prevent their evolution to invasive carcinoma. (2) To prevent development of second primary squamous cell cancers inpatients who have already undergone treatment of cancer. leukoplakia has been used to monitor responsiveness to certain chemoprevention agents in clinical trials. including retinoids, beta carotene, and vitamin E derivatives, retinoids have demonstrated the most efficacy in eliminating leukoplakia