Oral Cancer


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Oral Cancer

  1. 1. ORAL CANCER dr shabeel pn
  2. 2. Molecular changes <ul><li>Carcinogenesis is a genetic process that leads to a change in morphology and in cellular behavior. </li></ul><ul><li>Major genes involved in head and neck squamous cell carcinoma (HNSCC) include proto-oncogenes and tumor suppressor genes (TSGs) . </li></ul><ul><li>allelic loss at other chromosome regions, mutations to proto-oncogenes and TSGs </li></ul><ul><li>LOH has been reported to commonly involve chromosome arms 3p, 4q, 8p, 9p, 11q, 13q and 17p. </li></ul>
  3. 3. Proto-Oncogenes <ul><li>Increase cell growth and differentiation, are likely to be involved in carcinogenesis </li></ul><ul><li>Ras (rat sarcoma), cyclin-D1, myc , erb-b (erythroblastosis), bcl-1 , bcl-2 (B-cell lymphoma) </li></ul>
  4. 4. Tumor Suppressor Genes <ul><li>TSGs negatively regulate cell growth and differentiation. </li></ul><ul><li>Functional loss of TSGs is common in carcinogenesis. </li></ul><ul><li>p53 , Rb (retinoblastoma) and p16INK4A . </li></ul>
  5. 5. Molecular Model of Carcinogenesis
  6. 6. TNM Staging
  7. 7. Prognosis <ul><li>Stage 1: 80 – 90 % </li></ul><ul><li>Stage 2: 70 – 80 % </li></ul><ul><li>Stage 3: 30 – 50 % </li></ul><ul><li>Stage 4: 20 – 30 % </li></ul>
  8. 8. <ul><li>Local or regional spread of oral SCC is common </li></ul><ul><li>Distant metastases below the clavicle are rare. </li></ul><ul><li>Oral cancer occurring in the posterior aspect of the oral cavity and oropharynx and inferior in the mouth tends to be associated with a poorer prognosis </li></ul>
  9. 9. Death in Oral Cancer <ul><li>Erosion of major vessels </li></ul><ul><li>Erosion of the cranial base </li></ul><ul><li>Cachexia </li></ul><ul><li>Secondary RTIs </li></ul>
  10. 10. Viruses in Oral Cancer <ul><li>HSV – Co-carcinogenic effect with Tobacco </li></ul><ul><li>HPV – 16 & 18 </li></ul>
  12. 12. Management of Oral Cancer <ul><li>The choice of treatment depends on </li></ul><ul><li>cell type and degree of differentiation </li></ul><ul><li>site, size, and location of the primary lesion </li></ul><ul><li>lymph node status </li></ul><ul><li>presence of bone involvement </li></ul><ul><li>ability to achieve adequate surgical margins </li></ul><ul><li>ability to preserve speech </li></ul><ul><li>ability to preserve swallowing function </li></ul><ul><li>physical and mental status of the patient </li></ul><ul><li>assessment of the potential complications of each therapy </li></ul><ul><li>the experience of the surgeon and radiotherapist </li></ul><ul><li>Personal preferences and cooperation of the patient. </li></ul>
  13. 13. Treatment Options <ul><li>T 1 N 0, T 2 N 0 Surgery ± RT </li></ul><ul><li>RT -External Beam </li></ul><ul><li>-Brachytherapy </li></ul><ul><li>T 3 N 0 , T 4 N 0 Surgery and Post op RT </li></ul><ul><li>N + ± Chemotherapy </li></ul><ul><li>T 4b , N 3 , M + PALLIATION </li></ul><ul><li>- Primarily RT ± Chemo </li></ul>CURATIVE
  14. 14. Surgery <ul><li>Surgery may be the primary treatment or may be part of combined treatment with radiation therapy. </li></ul><ul><li>Indications </li></ul><ul><li>Tumors involving bone </li></ul><ul><li>When the side effects of surgery are expected to be less significant than those associated with radiation </li></ul><ul><li>Tumors that lack sensitivity to radiation </li></ul><ul><li>Recurrent tumor in areas that have previously received a maximum dose of radiotherapy </li></ul><ul><li>In palliative cases to reduce the bulk of the tumor </li></ul><ul><li>clinically positive cervical nodes - treatment of choice </li></ul>
  15. 15. <ul><li>Advantages </li></ul><ul><li>Short time – compliance </li></ul><ul><li>Specimen available for HPE </li></ul><ul><li>Helps in planning adjuvant treatment </li></ul><ul><li>No radiation sequelae </li></ul><ul><li>Disadvantages </li></ul><ul><li>Tissue & functional loss </li></ul><ul><li>Disfigurement </li></ul><ul><li>Infection </li></ul><ul><li>Bleeding </li></ul><ul><li>Mortality </li></ul>
  16. 16. Radiation <ul><li>Curative </li></ul><ul><li>As part of a combined radiation-surgery and/or chemotherapy </li></ul><ul><li>Palliative </li></ul>
  17. 17. <ul><li>Rationale </li></ul><ul><li>Radiation kills cells by interaction with water molecules in the cells </li></ul><ul><li>DNA is disrupted, and chromosomal damage occurs. </li></ul><ul><li>The affected cells may die or remain incapable of division. </li></ul><ul><li>Due to a greater potential for cell repair in normal tissue than in malignant cells and a greater susceptibility to radiation due to the higher growth fraction of cancer cells, a differential effect is achieved. </li></ul>
  18. 18. Fractionation <ul><li>Radiation therapy is delivered in daily fractions for a planned number of days. </li></ul><ul><li>1.8 – 2 Gy per day (Total 45 – 60 Gy) </li></ul><ul><li>The relatively hypoxic central tumor cells are less susceptible to radiotherapy, but they may become better oxygenated as peripheral cells are affected by radiation and are thus more susceptible to subsequent fractions of radiation </li></ul><ul><li>Less long term complications </li></ul>
  19. 19. <ul><li>SCCs are usually radiosensitive, and early lesions are highly curable. </li></ul><ul><li>The more differentiated the tumor, the less rapid will be the response to radiotherapy. </li></ul><ul><li>Exophytic and well-oxygenated tumors are more radiosensitive whereas large invasive tumors with small growth fractions are less responsive. </li></ul><ul><li>SCC that is limited to the mucosa is highly curable with radiotherapy; however, tumor spread to bone reduces the probability of cure with radiation alone. </li></ul><ul><li>Small cervical metastases may be controlled with radiation therapy alone </li></ul>
  20. 20. <ul><li>Palliative </li></ul><ul><li>Pain </li></ul><ul><li>Bleeding </li></ul><ul><li>Fungation </li></ul>
  21. 21. <ul><li>Advantages </li></ul><ul><li>No tissue or functional loss </li></ul><ul><li>No mortality </li></ul><ul><li>Regional nodes can be treated with less morbidity </li></ul><ul><li>Treatment of multiple primary possible </li></ul><ul><li>Better surgical salvage possible with failure </li></ul><ul><li>Disadvantages </li></ul><ul><li>Infrastructure </li></ul><ul><li>Treatment is protracted </li></ul><ul><li>Radiation sequelae </li></ul>
  22. 22. Radiation – Types <ul><li>External beam RT </li></ul><ul><ul><ul><ul><ul><li>Telecobalt </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Linear accelerator </li></ul></ul></ul></ul></ul><ul><li>Brachytherapy </li></ul><ul><ul><ul><ul><ul><li>Intracavitary - Ca Nasopharynx </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Interstitial - Ca Cheek, Tongue </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Mould therapy - Ca Palate </li></ul></ul></ul></ul></ul><ul><li>Internal Therapy </li></ul><ul><ul><ul><ul><ul><li>- Ca Thyroid </li></ul></ul></ul></ul></ul>
  23. 23. <ul><li>Advantages of Brachytherapy </li></ul><ul><li>Well defined volume treated </li></ul><ul><li>Highly localized </li></ul><ul><li>Minimal normal tissue complication </li></ul><ul><li>Short treatment time </li></ul><ul><li>Disadvantages </li></ul><ul><li>Invasive </li></ul><ul><li>Need expertise </li></ul>
  24. 24. Chemotherapy <ul><li>Curative </li></ul><ul><li>- Neoadjuvant (Induction) </li></ul><ul><li>- Adjuvant </li></ul><ul><li>- Concurrent: to treat micromets </li></ul><ul><li>Palliative </li></ul><ul><li>- Recurrence </li></ul><ul><li>- Metastatic disease </li></ul><ul><li>Drugs - Cisplatin, Methotrexate, 5 FU </li></ul>
  25. 25. PRE-TREATMENT ORAL AND DENTAL ASSESSMENT <ul><li>1.Reduce the risk or severity of complications </li></ul><ul><li>2.Reduce the risk of infection involving the dentition and mucosa </li></ul><ul><li>3.Minimize and manage the complications of hyposalivation. </li></ul>
  26. 26. <ul><li>Directed at maintenance of: </li></ul><ul><li>Mucosal and bony integrity </li></ul><ul><li>Dental and periodontal health </li></ul><ul><li>Salivary gland function </li></ul><ul><li>and </li></ul><ul><li>Prevention of potential complications of therapy. </li></ul>
  27. 27. TREATMENT PLANNING <ul><li>The radiation treatment plan is determined by tumor site, tumor size, the total volume to be radiated, the number of treatment fractions, the total number of days of treatment, and the tolerance of the patient. </li></ul><ul><li>Treatment planning in radiation therapy includes planning for the sparing of uninvolved tissues or organs. </li></ul><ul><li>The dose to the eye or spinal cord, salivary glands, alveolar bone, and soft tissue can be limited through the selection of the radiation source, field set-up, and shielding and by moving the uninvolved tissue out of the field. </li></ul>
  29. 31. <ul><li>Acute reactions (short term complications) occur during the course of radiotherapy because of direct tissue toxicity and possibly secondary bacterial irritation resulting in ‘ ulcerative mucositis’. </li></ul><ul><li>Chronic complications or late radiation reactions occur due to change in the vascular supply, fibrosis in connective tissue and muscle, and change in the cellularity of tissues. These complications develop slowly over months to years following treatment. </li></ul><ul><li>Hyperfractionation of radiation therapy may reduce the late complications but may increase the severity of the acute reactions. </li></ul>
  30. 32. Mucositis <ul><li>Ulcerative oral mucositis is a painful and debilitating condition that is a dose- and rate-limiting toxicity of cancer therapy. </li></ul><ul><li>The potential sequelae of mucositis consist of severe pain, increased risk for local and systemic infection, compromised oral and pharyngeal function, and oral bleeding. </li></ul><ul><li>Mucositis is the most common cause of pain during the treatment of cancer. </li></ul><ul><li>Hyperfractionation, combined chemo-radiotherapy, and the use of radiosensitizers cause increased severity of oral mucositis. </li></ul>
  31. 33. <ul><li>Pathogenesis </li></ul><ul><li>Cytotoxic chemotherapy and radiation therapy result in thinning of the epithelium and ultimately to loss of the barrier. Connective tissue and vascular elements are also affected. </li></ul><ul><li>Inflammatory/vascular and epithelial phase </li></ul><ul><li>Ulcerative/bacteriologic phase </li></ul><ul><li>Healing phase. </li></ul>
  32. 34. <ul><li>The first signs of mucositis may be </li></ul><ul><li>a white appearance to the mucosa, caused by hyperkeratinization and intraepithelial edema or pseudomembrane formation </li></ul><ul><li>a red appearance due to hyperemia and epithelial thinning. </li></ul><ul><li>Involves the nonkeratinized mucosa first. </li></ul><ul><li>Late changes in the mucosa reflect endarteritis and vascular changes associated with hypovascularity and with hyalinization of collagen. </li></ul><ul><li>With common fractions of 180 to 220 cGy per day, mucositis with erythema is noted in 1 to 2 weeks and increases throughout the course of therapy -to a maximum in 4 weeks- with persistence until healing occurs 2 or more weeks after the completion of therapy. </li></ul>
  33. 35. <ul><li>Management </li></ul><ul><li>-Systemic </li></ul><ul><li>(1) Pain management </li></ul><ul><li>- Analgesics: WHO ladder </li></ul><ul><li>- Adjuncts: Relaxation, imagery, biofeedback, hypnosis and transcutaneous electrical nerve stimulation </li></ul><ul><li>-  carotene </li></ul><ul><li>(2) Radioprotectors </li></ul><ul><li>- Amifostine: Scavenge free radicals </li></ul><ul><li>(3) Biologic Response Modifiers </li></ul><ul><li>- G-CSF, GM-CSF, Keratinocyte Growth Factor </li></ul>
  34. 36. <ul><li>- Topical </li></ul><ul><li>Diluting agents </li></ul><ul><li>Saline, bicarbonate rinses, frequent water rinses, dilute hydrogen peroxide rinses </li></ul><ul><li>Coating agents </li></ul><ul><li>Kaolin-pectin, aluminum chloride, aluminum hydroxide, magnesium hydroxide, hydroxypropyl cellulose, sucralfate </li></ul><ul><li>Lip Lubricants </li></ul><ul><li>Water-based lubricants, lanolin </li></ul><ul><li>Topical anesthetics </li></ul><ul><li>Dyclonine HCl, xylocaine HCl, benzocaine HCl, diphenhydramine HCl </li></ul><ul><li>Analgesic agents </li></ul><ul><li>Benzydamine HCl </li></ul>
  35. 37. Xerostomia <ul><li>Radiation > 3000 cGy </li></ul><ul><li>Dose related </li></ul><ul><li>Saliva flow reaches ‘zero’ with 6000 cGy </li></ul><ul><li>Serous acini affected more than mucous acini </li></ul><ul><li>May resolve within 6 months </li></ul><ul><li>If persisted for more than 1 yr, permanent damage </li></ul>
  36. 38. <ul><li>Management </li></ul><ul><li>Sialogogues </li></ul><ul><li>Pilocarpine </li></ul><ul><li>Bethanecol </li></ul><ul><li>Prophylactic </li></ul><ul><li>- Pilocarpine, Amifostine </li></ul>
  37. 39. Candidiasis Caries Osteoradionecrosis Taste abnormalities Musculoskeletal anomalies Dental anomalies Pain
  38. 40. <ul><li>Pain – Causes </li></ul><ul><li>Pain due to tumor </li></ul><ul><li>Pain due to cancer therapy - surgery </li></ul><ul><li>Pain due to radiotherapy </li></ul><ul><li>Pain due to chemotherapy </li></ul><ul><li>Pain unrelated to cancer or cancer therapy </li></ul>
  39. 41. <ul><li>Pain – Management </li></ul><ul><li>Topical anesthetic </li></ul><ul><li>Analgesics </li></ul><ul><li>Anti-inflammatory </li></ul><ul><li>Antimicrobial </li></ul><ul><li>Anticonvulsant </li></ul><ul><li>Anxiolytic </li></ul><ul><li>Antidepressant </li></ul><ul><li>Muscle relaxant </li></ul>