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CA LARYNX

ANATOMY, SUBSITE,SYMPTOMS, DIAGNOSIS ,NCCN GUIDELINES FOR THE MANAGEMENT , MULTIMODALITY APPROACH , RADIOTHERAPY, CHEMOTHERAPY , SURGERY

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CA LARYNX

  1. 1. Laryngeal CancerDr ANKITA SINGH PATEL MBBS,MD(KGMU) CONSULTANT Apex Hospital Cancer Institute TRAINING AND FELLOWSHIP Fortis Research Institute ,New Delhi Tata Memorial Hospital,MUMBAI Mob. 8765845035,9305421547 Email: dr.ankitapatel.onco@gmail.com WEBSITE: www.apexhospitalvaranasi.com
  2. 2. Anatomy – subdivision SITE SUBSITE Supraglottis Suprahyoid epiglottis Infrahyoid epiglottis Aryepiglottic fold(Laryngeal aspect) Arytenoids Ventricular bands (false cord) Glottis True vocal cords , including ant & Posterior commissure Subglottis Subglottis APEX HOSPITAL CANCER INSTITUTE
  3. 3. Vaezi, MF . Nature Clinical Practice Gastroenterology & Hepatology (2005) 2, 595-603 ANATOMY
  4. 4. Patient-related factors • Age and gender: MC after age 55. M:F 4:1 • Lifestyle: cigarette, cigar, and pipe smoking (2– 25× increase) and heavy alcohol consumption (2– 6× increase) • Past medical history • Weakened immunity Environmental factors Industrial chemicals: sulfuric acid mist, nickel or wood dust, or asbestos RISK FACTORS APEX HOSPITAL CANCER INSTITUTE
  5. 5. INCIDENCE OF CANCER BY SUBSITE Larynx Supraglottic 35% Glottic 65% Subglottic <1% Hypopharynx Pyriform sinus 65% Pharyngeal wall 20% Postcricoid 15%
  6. 6. Routes of spread for laryngeal and hypopharyngeal cancer Stage Local Extension 1. Most common manner of spread 2. Spread to cartilages initially causes sclerosis f/b erosion 3. Additional growth results in destruction and penetration of the cartilages (and precludes laryngeal-preservation strategies) Regional lymph node Metastasis 1. Lymphatic drainage depends on the Extent of primary tumor origin of the primary disease 2. Hypopharyngeal tumors can spread to the retropharyngeal nodal chain Distant Metastasis Bones , lungs APEX HOSPITAL CANCER INSTITUTE
  7. 7. Lymph node groups commonly involved in laryngeal and hypopharyngeal cancer Site Ipsilateral nodes (%) Contralateral nodes (%) I II III IV V I I I III IV V Supraglottic larynx 1% 39% 26% 8% 0% 5% 12% 5% 3% 3% Hypopharynx 1% 58% 42% 16% 11% 0% 7% 3% 1% 1% Hypopharyngeal tumors also spread to the retropharyngeal lymph nodes Source: Lindberg RD (1972) Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer 29:1446–1449 APEX HOSPITAL CANCER INSTITUTE
  8. 8. Commonly Observed Signs and Symptoms in Laryngeal and/or Hypopharyngeal Cancer STAGE DESCRIPTION Early laryngeal •Hoarseness •Change in voice quality Early hypopharyngeal oDifficulty swallowing oCervical adenopathy Advanced laryngeal and/or hypopharyngeal Hoarseness Difficulty swallowing Cervical adenopathy Weight loss Throat pain/referred pain in ear/s Airway obstruction
  9. 9. AJCC TNM classification of carcinoma of SUPRAGLOTTIS Stage Description Primary tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ Supraglottis T1 Tumor limited to 1 subsite of supraglottis, with normal vocal cord mobility T2 Tumor invades mucosa of more than 1 adjacent subsite of supraglottis or glottis or region outside the supraglottis, without fixation of the larynx T3 Tumor limited to larynx with vocal cord fixation and/or invades any of the following: postcricoid area, preepiglottic space, paraglottic space, and/or inner cortex of thyroid cartilage T4a Moderately advanced local disease: Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx T4b Very advanced local disease: Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures
  10. 10. GLOTTIS T1a Tumor limited to 1 vocal cord with normal mobility T1b Tumor involves both vocal cords with normal mobility T2 Tumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility T3 Tumor limited to the larynx with vocal cord fi xation and/or invasion of paraglottic space, an/or inner cortex of the thyroid cartilage T4a Moderately advanced local disease: Tumor penetrates the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx T4b Very advanced local disease: Tumor invades prevertebral space, encases carotid artery, or involves mediastinal structures
  11. 11. SUBGLOTTIS T1 Tumor limited to the subglottis T2 Tumor extends to vocal cord(s) with normal or impaired mobility T3 Tumor limited to larynx with vocal cord fixation T4a Moderately advanced local disease: Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx T4b Very advanced local disease: Tumor invades prevertebral space, encases carotid artery, or involves mediastinal structures
  12. 12. HYPOPHARYNX T1 Tumor limited to 1 subsite of hypopharynx and/or ≤2 cm in greatest dimension T2 Tumor invades more than 1 subsite of hypopharynx or an adjacent site, or measures >2 cm but ≤4 cm in greatest dimension T3 Tumor >4 cm in greatest dimension or with fi xation of hemilarynx or extension to esophagus T4a Moderately advanced local disease: Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, or central compartment soft tissue includes prelaryngeal strap muscles and subcutaneous fat T4b Very advanced local disease: Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures
  13. 13. STAGE GROUPING Stage 0 Tis N0 M0 Stage I T1 N0 M0 Stage II T2 N0 M0 Stage III T3 N0 M0 T1-3 N1 M0 Stage IVA T4a N0-1 M0 T1-4a N2 M0 Stage IVB T4b any N M0 any T N3 M0 Stage IVC any T any N M1 Early stage Advanced stage
  14. 14. Picture of glottic squamous cell carcinoma of the larynx. The tumor involves the anterior half of the left vocal cord. APEX HOSPITAL CANCER INSTITUTE
  15. 15. SUPRAGLOTTIC LARYNX APEX HOSPITAL CANCER INSTITUTE
  16. 16. ` APEX HOSPITAL CANCER INSTITUTE
  17. 17. MULTIDISCIPLINARY TEAM • The management of patients with head and neck cancers is complex. • All patients need access to the full range of support and specialists with the expertise in the management of patients with head and neck cancer for optimal treatment and follow up.  Head and neck surgery  Speeech and swallowing therapy  Radiation oncology  Clinical social work  Medical oncology  Nutrition support  Plastic and reconstructive surgery  Pathology(Cyto and Histo)  Specialised nursing care  Diagnostic radiology  Dentistry /Prosthodontics  Physical Medicine and rehabilitation APEX HOSPITAL CANCER INSTITUTE
  18. 18. LARYNX /HYPOPHARYNX CANCER SUSPECTED COMPLETE HISTORY AND PHYSICAL EXAMINATION ENDOSCOPY AND BIOPSY IMAGING LAB STUDIES INTERVENTION • CT or MRI or PET-CT With contrast and thin cuts of primary and neck • CECT Thorax • CBC • Serum Chemistry •Dental Prophylaxis if upper neck nodes require irradiation •Speech and Swallowing evaluation if needed APEX HOSPITAL CANCER INSTITUTE
  19. 19. ADVERSE FEATURES warrenting adjuvant treatment • Extracapsular nodal spread • +ve margin • pT3,4 • N2,N3 nodal disease • Perineural invasion • Vascular embolism(lymphovascular invasion) APEX HOSPITAL CANCER INSTITUTE
  20. 20. APEX HOSPITAL CANCER INSTITUTE
  21. 21. CLINICAL STAGING TREATMENT OF PRIMARY AND NECK ADJUVANT TREATMENT Carcinoma in situ Endoscopic resection(preferred) Or RT Amenable to Larynx preserving(c onservation) surgery (T1- T2 or select T3) RT Partial laryngectomy / endoscopic or open resection as indicated or neck desection as indicated. No adverse features OBSERVE Adverse features CRT/RT APEX HOSPITAL CANCER INSTITUTE
  22. 22. CLINICAL STAGING TREATMENT OF PRIMARY AND NECK T3 requiring( amenable to total laryngecto my) (N0,N1) RT/CRT PRIMARY SITE: CR (N0) PRIMARY SITE: CR (N+) Residual in neck Neck dissection CR Post treatment evaluation -ve Observ e Neck dissecti on +v Primary site: residual tumor Salvage surgery and neck dissection SURGERY N0 : Laryngectomy with I/L thyroidectomy No adverse features N1: Laryngectomy with I/L thyroidectomy as indicated, I/L neck dissection , or B/L neck dissection adverse features CRT Induction chemother apy APEX HOSPITAL CANCER INSTITUTE
  23. 23. CLINICAL STAGING TREATMENT OF PRIMARY AND NECK T3 requiring(am enable to total laryngectomy ) (N2,N3) CRT/RT PRIMARY SITE: Complete clinical response Residual in neck Neck dissection Complete clinical response of neck Post treatment evaluation -ve Observe Neck dissection +v Primary site: residual tumor Salvage surgery and neck dissection Surgery Laryngectomy with I/L thyroidectomy as indicated, I/L neck dissection , or B/L neck dissection No adverse features adverse features CRT/RT Induction chemother apy APEX HOSPITAL CANCER INSTITUTE
  24. 24. RESPONSE ASSESSMENT Response after induction chemother apy Primary site: CR Definitive RT Residual in neck Neck dissection CR of neck Post treatment evaluation -ve Observe +ve Neck dissection Primary site : PR RT / CRT CR Observe Residual Salvage surgery Primary site <PR Surgery No adverse features RT Adverse features ECE +/ +ve margin CRT Other risk factor CRT
  25. 25. CLINICA L STAGING TREATMENT OF PRIMARY AND NECK T4a,any N Surgery N0 Total laryngectomy + thyroidectomy as indicated +- U/L or B/L neck dissection RT Or CRT Observe for highly selective cases N1 Total laryngectomy + thyroidectomy as indicated + I/L +- C/L neck dissection N2-3 Total laryngectomy + thyroidectomy as indicated +- I/L or B/L neck dissection Selected T4a patients who decline surgery CRT Primary Site:Complet e clinical response Residual in neck Neck dissection CR of neck Post treatment evaluation -ve Observatio n +ve Neck dissection Primary Site: Residual tumor Salvage surgery and neck dissection Induction chemo APEX HOSPITAL CANCER INSTITUTE
  26. 26. APEX HOSPITAL CANCER INSTITUTE
  27. 27. CLINICAL STAGING TREATMENT OF PRIMARY AND NECK PATHOLOGY STAGE ADJUVANT TREATMENT Amenable to larynx preserving (conservatio n) surgery(Mo st T1-2 ,N0) Selected T3 patients Endoscopic resection +- neck desection Or Open partial supraglottic laryngectomy +- neck dissection Node –ve (T1-T2 ,N0) One Node +ve,no adverse feature RT +ve node;+ve margin Adverse features+ Reresection Or RT/CRT Adverse features;ECE CRT/RT Node –ve , T3-T4a,N0 RT Definitive RT APEX HOSPITAL CANCER INSTITUTE
  28. 28. v CLINICAL STAGING TREATMENT Requiring (amenable to) total laryngectomy( T3,N0) CRT/RT Primary Site:CR Primary site:residual Salvage surgery and neck dissection Laryngectomy,I/L thyroidectomy with I/L or B/L neck dissection Adverse feature RT/CRT RT Induction Chemotherapy APEX HOSPITAL CANCER INSTITUTE
  29. 29. CLINICAL STAGING TREATMENT OF PRIMARY AND NECK Amenable to larynx- preserving (conservatio n) surgery(T1-2 ,N+ and selected T3,N1) CRT/RT Primary site:CR Residual in neck Neck dissection (ND) CR of neck Post treatment evaluation -ve obs +ve ND RT Primary site: residual tumor Salvage surgery +neck dissection as indicated Partial Supraglottic laryngectomy and neck dissection No adverse feature Observe / RT Adverse feature CRT/RT Induction chemotherap y APEX HOSPITAL CANCER INSTITUTE
  30. 30. CLINICAL STAGING TREATMENT OF PRIMARY AND NECK Requiring (amenable to) total laryngectom y(Most T3,N2-N3) CRT/RT Primary site:CR Residual in neck Neck dissectio n (ND) CR of neck Post treatment evaluation -ve obs +ve ND Primary site: residual tumor Salvage surgery +neck dissection as indicated Laryngectom y,I/L thyroidectom y with neck dissection No adverse feature RT Adverse feature CRT/RT Induction chemotherap y APEX HOSPITAL CANCER INSTITUTE
  31. 31. RESPONSE ASSESSMENT AFTER NACT Response after induction chemothera py Primary site: CR Definitive RT Residual in neck Neck dissection CR of neck Post treatment evaluation -ve Observe +ve Neck dissection Primary site : PR RT Or CRT CR Observe Residual Salvage surgery Primary site <PR Surgery No adverse features RT Adverse features RT/CRT APEX HOSPITAL CANCER INSTITUTE
  32. 32. CLINICAL STAGING T4a,N0- N3 Laryngectomy , thyroidectomy as indicated with I/L or B/L neck dissection Risk factor + RT/CRT T4a,N0- N3 patients who decline surgery RT/CRT Primary Site: CR Residual neck Neck dissection CR Neck Post treatment evaluation -ve Observe +ve Neck dissection Primary Site: Residual disease Salvage surgery + neck dissection Induction chemotherapy APEX HOSPITAL CANCER INSTITUTE
  33. 33. APEX HOSPITAL CANCER INSTITUTE
  34. 34. CLINICAL STAGING TREATMENT OF PRIMARY AND NECK PATHOLOGY STAGE ADJUVANT TREATMENT Most T1N0 , Selected T2NO ,N0 Amenable to larynx preserving (conservation) surgery Definitive RT Pimary Site:Complete clinical response Pimary Site: residual tumor Salvage surgery + neck dissection as indicated Surgery: Partial laryngopharyngect omy (open or endoscopic ) + I/L or B/L neck dissection. No adverse feature Adverse feature RT/CRT APEX HOSPITAL CANCER INSTITUTE
  35. 35. CLINICAL STAGING TREATMENT T2-3 , any N if requiring (amenable to ) pharyngecto my with total laryngectom y); T1,N+ Induction Chemotherapy CR RT/CRT PR Surgery or RT/CRT Laryngophary ngectomy + neck dissection Including level VI No adverse features Adverse features CRT/RT CRT/RT Primary site:compl ete clinical response Residual in neck Neck dissection Complete clinical response of neck Post treatment evaluation -ve Observe +ve Neck dissectio n Primary site : residual tumor Salvage surgery + neck dissection as indicated APEX HOSPITAL CANCER INSTITUTE
  36. 36. CLINICAL STAGING T4a,any N Surgery and Neck dissection Adverse features RT/CRT Induction chemother apy CR/PR CRT/RT <PR or progression Salvage surgery + neck dissection No adverse features Adverse features RT/CRT CRT/RT Primary site: complete clinical response Residual in neck Neck dissection Complete clinical response of neck Post treatment evaluation Negative Observe Positive Neck dissection Primary site : residual tumor Salvage surgery + neck dissection as indicated APEX HOSPITAL CANCER INSTITUTE
  37. 37. SUMMARY OF GUIDELINE STAGE TREATMENT Tis Endoscopic removal (stripping/laser) or definitive RT T1-2N0 glottic Definitive RT. Advantage of RT is that failures can be salvaged with partial laryngectomy and still have third chance with salvage total laryngectomy. Alternative, cordectomy or partial laryngectomy ± selective neck dissection. Post-op RT for close/+ margin, PNI, LVSIv APEX HOSPITAL CANCER INSTITUTE
  38. 38. T1-2N0 supraglottic Definitive RT Or Partial Supraglottic laryngectomy ± selective neck dissection. Post-op chemo-RT for + margin; post- op RT for close margin, PNI, LVSI APEX HOSPITAL CANCER INSTITUTE
  39. 39. Resectable T1-2N+, T3N0/+ requiring total laryngectomy Concurrent chemo-RT as in RTOG 91– 11(preferred). If < CR , salvage surgery and neck dissection may be performed. If residual neck mass or initial N2-3, post-RT neck dissection Considered Alternative is total laryngectomy, and I/L or B/l (N0-1) or bilateral comprehensive neck dissection (N2-3). Post-op chemo-RT high risk disease. Induction chemo × 3c may be considered. If CR or PR, proceed with concurrent chemo-RT as above. If < PR or progression, proceed to surgery and neck dissection as indicated
  40. 40. Resectable T4N0/+ Total laryngectomy and I/L or B/L neck dissection followed by post-op chemo-RT Alternative for selected patients is definitive concurrent chemo-RT as in RTOG 91–11. Induction chemotherapy may be considered Unresectable T3-4 or N+ Concurrent chemo-RT. If unable to tolerate chemo, definitive RT with concomitant boost (CB) and consider concurrent cetuximab APEX HOSPITAL CANCER INSTITUTE
  41. 41. HYPOPHARYNX Early T1-2 not requiring total laryngectomy (T1N0-1, small T2N0, T1N2) Definitive RT. If < complete response, salvage surgery and neck dissection as indicated. If complete response, neck dissection considered for N2-3 Alternatively, partial laryngopharyngectomy and I/L or B/L selective neck dissection (N0) or comprehensive neck dissection (N+). Post-op chemo-RT for high risk factors. APEX HOSPITAL CANCER INSTITUTE
  42. 42. T2-4N0/+ requiring total laryngectomy Concurrent chemo-RT as extrapolated from RTOG 91–11. Or, induction chemo ×2c (with a third cycle if PR). If CR at primary site, proceed with definitive RT (³70 Gy). If primary site has only PR, proceed with concurrent chemo- RT. Nonresponders to induction chemo should undergo surgery → post-op RT or chemo-RT as indicated. If residual neck mass after definitive RT or initial N2-3, post- RT neck dissection considered Or, laryngopharyngectomy and selective (N0) or comprehensive neck dissection (N+ or T4). Post-op chemo-RT forhigh risk factors. Unresectable T3-4 or N+ Concurrent chemo-RT. If unable to tolerate chemo, definitive RT with CB APEX HOSPITAL CANCER INSTITUTE
  43. 43. FOLLOW-UP SCHEDULE AND EXAMINATIONS SCHEDULE FREQUENCY First follow-up 2 weeks after radiation therapy Years 0–1 Every month Years 1–2 Every 2 months Years 2–3 Every 3 months Years 3+ Every 6 months APEX HOSPITAL CANCER INSTITUTE
  44. 44. 1. Posttreatment baseline imaging recommended, and thereafter, as clinically indicated. 2. CXR annually. 3. TSH every 6–12 month if neck irradiated. 4. Speech, swallow, dental, and hearing evaluations and rehabilitation as indicated. 5. Smoking cessation counseling If recurrence is suspected but biopsy is negative, follow closely (at least monthly) until it resolves. APEX HOSPITAL CANCER INSTITUTE
  45. 45. STAGE 2/5 YEAR OS SURVIVAL LARYNX HYPOPHARYNX 2 year 5 year 2 year 5 year I 95 % 88% 65% 35% II 80% 60% 60% 30% III 70% 50% 50% 30% IV 60% 35% 35% 15% Used with permission from the American Joint Committee on Cancer (AJCC), Chicago, IL. APEX HOSPITAL CANCER INSTITUTE
  46. 46. Radiotherapy APEX HOSPITAL CANCER INSTITUTE E. 48 LARYNGEAL CANCER MULTIMODALITY APPROACH WE PROVIDE
  47. 47. Chemotherap y Use of antineoplastic drugs to kill and destroy TUMOR CELLS. 49 APEX HOSPITAL CANCER INSTITUTE
  48. 48. TARGETED THERAPY 50 APEX HOSPITAL CANCER INSTITUTE.APEX HOSPITAL CANCER INSTITUTE
  49. 49. Cancer Targets From National Cancer Institute, US National Institutes of Health. 51APEX HOSPITAL CANCER INSTITUTE
  50. 50. TK TKATP ATP Cell Proliferation Antiapoptos is Angiogenesis Gene Transcription Cell Cycle Progression + MetastasesSurviva l Tumor Cell Stimulation 52
  51. 51. TK TK Strategies to Inhibit Signaling - - tyrosine kinase inhibitors “-ibs” Anti- mAbs “-mab” ATP 53 APEX HOSPITAL CANCER INSTITUTE.
  52. 52. RADIOTHERAPY 54 APEX HOSPITAL CANCER INSTITUTE
  53. 53. MECHANISM OF ACTION 55 RADIATION RADIATION APEX HOSPITAL CANCER INSTITUTE
  54. 54. Radiotherapy 1) Teletherapy : Conventional 3DCRT IMRT IGRT VMAT BIGRT (ONLY AT APEX HOSPITAL CANCER INSTITUTE ) 2) Brachytherapy: Intracavitary Intraluminal Interstitial Mould therapy 56 APEX HOSPITAL CANCER INSTITUTE.APEX HOSPITAL CANCER INSTITUTE
  55. 55. TELETHERAPY 57 APEX HOSPITAL CANCER INSTITUTE
  56. 56. TECHNICAL ESSENTIALS OF EXTERNAL BEAM RADIATION Co60 machine Linear Accelerator APEX HOSPITAL CANCER INSTITUTE. Thankyou Cobalt for the service to mankind…Time to bid goodbye… 58
  57. 57. Why to sacrifice if we have better option !! 59 APEX HOSPITAL CANCER INSTITUTE.APEX HOSPITAL CANCER INSTITUTE
  58. 58. WHAT ARE THE MODERN MODALITIES? ARE THEY BETTER THAN CONVENTIONAL TREATMENT? 60 APEX HOSPITAL CANCER INSTITUTE.APEX HOSPITAL CANCER INSTITUTE
  59. 59. Conventional therapy 61 APEX HOSPITAL CANCER INSTITUTE.APEX HOSPITAL CANCER INSTITUTE
  60. 60. Intensity modulated radiotherapy (IMRT) 62 APEX HOSPITAL CANCER INSTITUTE.APEX HOSPITAL CANCER INSTITUTE
  61. 61. 63 APEX HOSPITAL CANCER INSTITUTE.APEX HOSPITAL CANCER INSTITUTE
  62. 62. 64 APEX HOSPITAL CANCER INSTITUTE
  63. 63. E. 65 APEX HOSPITAL CANCER INSTITUTE
  64. 64. 66 APEX HOSPITAL CANCER INSTITUTE
  65. 65. APEX HOSPITAL CANCER INSTITUTE
  66. 66. For Highly Conformal Highly Precise Radiation therapy with organ preservation……. STEPS
  67. 67. IMMOBILISATION by thermoplastic cast 69 APEX HOSPITAL CANCER INSTITUTE
  68. 68. RTP (RADIOTHERAPY PLANNING SCAN) SCAN by laser-ct and fiducials 70 APEX HOSPITAL CANCER INSTITUTE
  69. 69. TELETHERAPY PLANNING SYSTEM(US FDA APPROVED) 71 APEX HOSPITAL CANCER INSTITUTE
  70. 70. TPS (Teletherapy Planning system) (Xio , Monte Carlo Based Planning System as approved by US FDA and AERB) 09-04-2016 E 72 APEX HOSPITAL CANCER INSTITUTE
  71. 71. For small cancers in the vocal cords it is possible to keep the radiation far away from other normal structures 73 APEX HOSPITAL CANCER INSTITUTE.APEX HOSPITAL CANCER INSTITUTE
  72. 72. EXECUTION Apex Hospital Cancer Institute 74 APEX HOSPITAL CANCER INSTITUTE.
  73. 73. INSTIT UTE. Verification by CBCT( cone beam CT)75 APEX HOSPITAL CANCER INSTITUTE
  74. 74. Patient comes at fixed time,gets treated in 5 min and goes back. No admission No iv infusion Can do household work. Daily Treatment76 APEX HOSPITAL CANCER INSTITUTE
  75. 75. THANKYOU ..
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ANATOMY, SUBSITE,SYMPTOMS, DIAGNOSIS ,NCCN GUIDELINES FOR THE MANAGEMENT , MULTIMODALITY APPROACH , RADIOTHERAPY, CHEMOTHERAPY , SURGERY

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