Oropharynx cancer practical target delineation 2013 apr


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Oropharynx cancer practical target delineation 2013 apr

  1. 1. General Principles and Practical Pointsin Target Delineation: Oropharynx CaYong Chan Ahn, MD, PhDDept of Radiation OncologySamsung Medical CenterSungkyunkwan University School of Medicine
  2. 2. Anatomy
  3. 3. Tonguebase (Vallecula)TonsilAnt pillaFossaPost pillaSoft palate
  4. 4. Soft Palate• Soft palate is thin, mobile muscle complexseparating nasopharynx from oropharynx.• It is contiguous laterally with tonsillar pillars.• Epithelium:– Oral side is squamous– Nasopharyngeal surface is respiratory
  5. 5. Tonsillar Fossa• Boundaries:– Ant -- ant tonsillar pillar (palatopharyngealmuscle)– Post -- post tonsillar pillar (palatopharyngealmuscle)– Inf -- glossotonsillar sulcus andpharyngoepiglottic fold– Lat -- pharyngeal constrictor muscle and itsfascia, mandible, and lateral pharyngeal space
  6. 6. Tonguebase• Boundaries:– Ant -- circumvallate papillae– Lat -- glossotonsillar sulci– Post -- epiglottis• Vallecula:– Ttransition from tonguebase to epiglottis• Tonguebase musculature is contiguouswith oral tongue.
  7. 7. Natural History& Patterns of Spread
  8. 8. Primary Lesion Spread is dictated by local anatomy, and eachanatomic site has its own peculiar patterns. Muscle invasion – common (may spread alongmuscle or fascial planes) Bone and cartilage act as barrier to spread Parapharyngeal space invasion – sup~infspread from base of skull to low neck Perineural invasion Vascular space invasion
  9. 9. Ant Tonsillar Pillar -- Primary• Usually diagnosed early when superficial– Usually with indistinct margins– May be red, white, or mixture• May develop central ulcer with rolledmargin– Sup/Med -- to soft palate, post hard palate, andmaxillary gingiva.– Ant/Lat -- to retromolar trigone, postgingivobuccal sulcus, buccal mucosa, adjacenttongue.
  10. 10. Ant Tonsillar Pillar -- Primary• Advance lesions:– Mandible invasion– Skullbase and nasopharynx occurs lateassociated with medial pterygoid muscle andplate invasion (trismus and temporal pain).
  11. 11. Tonsillar Fossa -- Primary• Initial lesions:– Tend to be exophytic with central ulcerationplus an iniltrative component.– Some develop submucosally -- neck nodeswith no obvious tonsillar lesion.• Extension to posterior tonsillar pillar andoropharyngeal wall occurs early.• Invasion into glossotonsillar sulcus andtonguebase occurs in 25%.
  12. 12. Tonsillar Fossa -- Primary• Advance lesions:– Penetrate to parapharyngeal space  accessto skull base.– Cranial nerve involvement is uncommon.– May invade mandible, nasopharynx, andpyriform sinus.
  13. 13. Post Tonsillar Pilla -- Primary• Early lesions are uncommon.• May spread inferiorly alongpalatopharyngeal muscle to its insertionsinto middle pharyngeal constrictor,pharyngoepiglottic fold, and posteriorborder of thyroid cartilage.• Also, lymphatic trunks of posterior tonsillarpillar are theoretically more likely to spreadto junctional (parapharyngeal) and level Vnodes.
  14. 14. Soft Palate -- Primary• Nearly all lesions occur on oral side.• Earliest tumors are red lesions with illdefined borders.• White lesions may be leukoplakia,carcinoma in situ, or early invasivecarcinoma.• Multiple sites involvement with normal-appearing intervening mucosa may occur.• Most carcinomas are diagnosed while stillconfined to soft palate.
  15. 15. Soft Palate -- Primary• Spread occurs first to tonsillar pillars andhard palate.• Lateral spread may penetrate superiorconstrictor muscle and skull base and mayrarely extend to cranial nerves inparapharyngeal space.• Involvement of lateral wall(s) ofnasopharynx may occur in advancedlesions.
  16. 16. Tonguebase -- Primary• Usually remains in tongue unless it beginsat peripheral margin.• Vallecular lesions:– Post -- to lingual surface of epiglottis.– Lat -- to lateral pharyngeal wall and anteriorwall of pyriform sinus along pharyngoepiglotticfold.– Inf -- to preepiglottic space via thinhyoepiglottic ligament.
  17. 17. Tonguebase -- Primary• Lateral tonguebase lesions:– May invade glossotonsillar sulcus andeventually escape into neck (no effectivemusculature barrier).• Advanced lesions spread to larynx, oraltongue, and parapharyngeal space.
  18. 18. Lymphatic Spread Predictors of LN meta: Histologic type Differentiation of tumor Primary lesion size Vascular space invasion Capillary lymphatics density Recurrence
  19. 19. Lymphatic Spread Subclinical disease in clinically (-) LN: Positive nodes by elective neck dissection Regional recurrence by F/U after no neck Tx
  20. 20. Subclinical Disease Defined as Disease statistically known to be present Cannot be seen or palpated in areasaccessible to physical examination Cannot be seen on highly efficient imagingstudies From barely detectable microscopic focus toundetected 2 cm node completely replaced bytumor
  21. 21. Incidence of Subclinical Disease
  22. 22. Lymphatic Spread Orderly progression Well-lateralized lesions  spread toipsilateral neck Lesions on or near midline and lateralizedtongue base and nasopharyngeal lesions may spread to both sides, and tend to spreadto bulky side
  23. 23. Incidence of Subclinical Disease (%)
  24. 24. Lymphatic Spread Contralateral disease in clinically (+) LN: Large or multiple LN Lymphatic pathways obstruction by surgeryor RT Shunting is mainly through submental space Level II LN is most commonly involved incontralateral metastases from well-lateralizedlesions
  25. 25. Lymphatic Spread Skip metastasis can occur: If unusual LN site involvement (+) search for second primary Retrograde LN metastases in ipsilateralaxilla if lower neck LN involved
  26. 26. Lymphatic Spread Retropharyngeal LN involvement: Became easier with CT and MRI Risk of retropharyngeal adenopathy isrelated to clinically involved LN and primarysite
  27. 27. Lymphatic Spread(Oropharynx Cancer Summary)Tonguebase Tonsillar fossa Ant pillar Soft palate1st echelon II II Ib/II Ib/VcN(+) 75% 75% 45% 55%Contralateral 30% 10% 5% 15%Occult 40~50% 50~60% 10~15% 20%
  28. 28. Distant Metastasis Same for stage for stage regardless of Tx modality Related more to cN and involved LN location than: <10% for cN0-1 disease 30% for cN3 disease or cN1-2 nodes with low neck LNinvolvement Lung is most common: About 1/2 of first metastatic sites 50%, 80%, and 90% at 9 months, 2 years, and 3 years Risk doubles if recurrence above clavicles
  29. 29. Neck Management Issues
  30. 30. Management of N0 Neck Occult cervical LN metastases: 20~30% Influenced by multiple factors Size and location of primary cancer Depth of invasion Tumor differentiation Elective LN dissection or irradiation isneeded as part of standard management
  31. 31. Policy of Elective Neck Treatment Same modality of treating primary site RT + ENI  little additional morbidity Surgery + MND  modest additionalmorbidity Survival advantage is small and usuallyoffset by Tx failures, second cancer, andintercurrent disease
  32. 32. Surgical Management of Neck Radical neck dissection is the standard involves complete removal of the lymphaticpathways within the neck SCM muscle, SAN, and JV are routinelysacrificed More conservative surgical procedures sparing of specific anatomic structures (i.e.,SAN and SCM muscle)
  33. 33. Selective Neck Dissection: Rationales Better understanding of diseasecharacteristics More clinical experience and data Better anatomic imaging tools (CT and MR) Functional and physiologic imaging toolsavailable Intra-operative therapeutic decision Systematic use of intraop frozen section Concept of sentinel lymph node
  34. 34. Types of Neck DissectionsClassificationLevel of LNRemovedStandard RND I, II, III, IV, VModified RND I, II, III, IV, VSelective NDSupraomohyoid I, II, IIILateral II, III, IVPosterlateral II, III, IV, VAnterior compartment IVExtended ND
  35. 35. Sentinel Lymph Node (SLN) The 1st LN to receive lymphatic drainagefrom a primary tumor. If it contains metastatic tumor, this indicatesthat other LN may contain tumor. If it dose not contains metastatic tumor,other LN are not likely to contain tumor. Initially investigated for LN staging incutaneous melanoma Increasing clinical application in breastcancer and H/N cancer
  36. 36. Neck IrradiationEveryone knows that elective neckirradiation is an essential component ofradical RT for almost all H/N cancersUsually 45~50 Gy/5 weeksUsually (but not always) to entire neckUsually regarded ‘less morbid’ than surgery
  37. 37. Factors to be Considered in ENI Primary site Histologic grade, vascular space invasion Depth of invasion, size of primary lesion Risk for bilateral subclinical disease Difficulty of neck examination Relative morbidity of extending ENI vs risk ofsubclinical disease Patients’ compliance to follow-up evaluations Patients’ suitability for RND in case ofrecurrence after RT
  38. 38. Target Delineation Issues:From 2D era to 3D era
  39. 39. Simulation films of 2 cases (T3N0 supraglottic larynx, T2N0 mobile tongue)were sent to 16 experienced HN radiation oncologists in 11 departments in TheNetherlands.Q1. To delineate treatment portals covering neck (and primary tumor).Q2. To indicate neck LN regions for elective RT.
  40. 40. 2 Ports (I)3 Ports (II)
  41. 41. Rotterdam and Brussels have independently published guidelines fordefinition and delineation of CT-based neck nodal Levels I–VI.Rotterdam and Brussels differed slightly in translating original surgicallevel definitions proposed by 2002 AAO-HNS to CT guidelines.Taking surgical 2002 AAO-HNS classification as a reference,adjustments are proposed for Rotterdam and Brussels delineationprotocols to arrive at unified CT-based neck nodal classification.
  42. 42. Practical Points
  43. 43. ’04 Radiology
  44. 44. ’04 Radiology
  45. 45. ’04 Radiology
  46. 46. ’09 JKMS
  47. 47. Plan Parameters
  48. 48. DVH (Case 2)
  49. 49. Ipsilateral Parotid Contralateral ParotidDVH (Case 2)
  50. 50. Institute1 2 3 4 5Case 1 Gross Lesion (Primary) 99 99 95 96 97Gross Lesion (LN) 100 100 100 100 100Case 2 Gross Lesion (Primary) 100 100 100 100 100Gross Lesion (LN) 96 93 89 93 88Case 1 Ipsilateral Parotid 52 51 24 23 11Contralateral Parotid 2 10 2 1 2Case 2 Ipsilateral Parotid 100 98 16 90 15Contralateral Parotid 70 33 1 24 8TCP and NTCP (Case 2)
  51. 51. Problems with GTV Delineation• GTV is poorly appreciated by imaging andFNABx.– (+) and close resection margin at surgery– Evidenced by partial organ surgery studies• Causes of uncertainty:– Submucosal spread, perineural invasion, non-cohesivemargins– Poor sensitivity/specificity of GTV by CT, MR, PET– Non-geometric tumor spread through tissueE-Contouring @ ASTRO 2012
  52. 52. E-Contouring @ ASTRO 2012
  53. 53. E-Contouring @ ASTRO 2012
  54. 54. E-Contouring @ ASTRO 2012
  55. 55. E-Contouring @ ASTRO 2012
  56. 56. E-Contouring @ ASTRO 2012
  57. 57. How I Do?
  58. 58. Definition DescriptionGTV Palpable or visiblediseasePhysical examination, radiographsCTV GTV + expansion formicroscopic spreadKnowledge of patterns of spread (onco-anatomy)PTV CTV + expansion forsetup error and organmotionImaging studies (fluoroscopy or 4D CT todefine degree of motion) and reproducibility/stability of mobilization/localization systems
  59. 59. ICRU Nomenclature for Volumes
  60. 60. Why 45~50 Gy for ENI?First documented by Gilbert Fletcher in 1972(Cancer, 29:1450~1454)45~50 Gy/5 weeks to initially uninvolved areasElective RT Partial neck Whole neck# of patients 185 284# with N3 disease 12 (6.5%) 100 (35.2%)New neck disease 22 (12.0%) 5 (1.7%)
  61. 61. Is ENI without Morbidity?Aerodigestive track: swallowing discomfort,pain, voice change, dyspnea, cough, sputumSkin and soft tissue: dermatitis, lymphedema,fibrosis, joint stiffness, soft tissue necrosisGlandular structures: dry mouth (dental caries),dry eyeSkeletal system: osteonecrosis, chondronecrosisOthers: fatigue, anorexia, nausea, secondcancer
  62. 62. ENI vs Observation?Risk-benefit ratio should be consideredAssumptionsSame local control rate regardless of ENIEfficiency of regional control by ENI = 90%Salvage rate of surgery (if no ENI) = 60%Risk of severe morbidity by ENI = 3%
  63. 63. Risk of Subclinical DiseaseENI 30% 20% 10%NoYes
  64. 64. Give-up Old Concept!More accurate imagingfor treatment planningHigh precision RTMultimodal imagingCT, MRI, PET, etc3D-CRT, IMRT, SRT, IGRTParadigm shift:36~40 GySelective neckClinical evidences
  65. 65. Strategies for shrinking tumor:• Shrinking field by 3D-CRT• Dose painting by IMRT• Both
  66. 66. Case 27**1: Lt Tonsil ca, Sq, cT2N1 (F/46)• Definitive CCRT (3D shrinking field):– ’09/5/8 ~ 6/25: 70 Gy/35 Fx’s(36 Gy/18 Fx’s + 18 Gy/9 fx’s + 16 Gy/8 Fx’s)– Concurrent CDDP #3 (100 mg/m2)
  67. 67. Case 27**1: 1st Plan upto 36 Gy/18 Fx’s
  68. 68. Case 27**1: 1st Plan upto 36 Gy/18 Fx’s26 Gy/13 Fx’s
  69. 69. Case 27**1: 2nd Plan upto 54 Gy/27 Fx’s
  70. 70. Case 27**1: 2nd Plan upto 54 Gy/27 Fx’s46 Gy/23 Fx’s
  71. 71. Case 27**1: 3rd Plan upto 70 Gy/35 Fx’s
  72. 72. Case 27**1: 3rd Plan upto 70 Gy/35 Fx’s60 Gy/30 Fx’s
  73. 73. ’09-Apr ’10-Jan ’12-OctPre-RT 8M 3Y 7M
  74. 74. ’09-Apr ’10-Jan ’12-OctPre-RT 8M 3Y 7M
  75. 75. ’09-Apr ’10-Jan ’12-OctPre-RT 8M 3Y 7MQ: Dry mouth?A: “Negligible!”
  76. 76. Case 28**6: Tonguebase ca, Sq, cT2N2 (M/59)• Definitive CCRT (SIB using Tomotherapy):– ’09/8/18 ~ 9/29: 66 Gy/30 Fx’s (39.6 Gy/18 Fx’s +26.4 Gy/12 fx’s)– Concurrent CDDP #3 (100 mg/m2)
  77. 77. Case 28**6: 1st Plan upto 39.6 Gy/18 Fx’s
  78. 78. Case 28**6: 1st Plan upto 39.6 Gy/18 Fx’s28.6 Gy/13 Fx’s
  79. 79. Case 28**6: 2nd Plan upto 66 Gy/30 Fx’s
  80. 80. Case 28**6: 2nd Plan upto 66 Gy/30 Fx’s
  81. 81. Case 28**6: 1st vs 2nd Target Volumes
  82. 82. ’09-Aug ’09-Dec ’13-FevPre-RT 4M 3Y 6M
  83. 83. ’09-Aug ’09-Dec ’13-FevPre-RT 4M 3Y 6MQ: How R U doing?A: “Doing fine!”
  84. 84. Comparison of Dose Schedules at SMC3D RT TomoTherapyMain concept Serial shrinking field Dose paintingSubclinicaldisease36 Gy/18 Fx’s 36 Gy/18 Fx’s 36 Gy/18 Fx’sEquivocal lesion 54 Gy/27 Fx’s60~63.6 Gy/Fx’s(2*30 or 2.2*18 + 2*12)Definite lesion 70 Gy/35 Fx’s66 Gy/30 Fx’s(2.2*30)69.4 Gy/30 Fx’s(2.2*18 + 2.4*12)Number plans 3 times 2 timesDuration 7 weeks 6 weeks
  85. 85. Has It Worked Well?
  86. 86. Finished proof reading a week ago.And will show up on Head and Neck soon!
  87. 87. Radiation Therapy• 3D-CRT (7 weeks):– 70 Gy/35 Fx’s in 35 patients• Helical Tomotherapy (6 weeks):– 66 Gy/30 Fx’s (2.2 Gy*30 Fx’s) in 14 patients– 68.4 Gy/30 Fx’s (2.2 Gy*18 Fx’s + 2.4 Gy*12 Fx’s)in 10 patients• Routine adaptive re-plan during RT:– 2nd CT simulation after median 15 (12–17) Fx’s
  88. 88. Treatment Outcomes• Median F/U = 41.3 (9.3–73.5) months• Response rate = 96.6%:– CR 32 (54.2%)/PR in 25 (42.4%)/SD in 1 (1.7%)/PD in 1 (1.7%)• 6 deaths (including 1 intercurrent death)• 10 treatment failures53 2RegionalLocalDistantAt 1 year At 3 yearsPFS 89.8% 82.7%LC 91.5% 86.2%OS 92.7%
  89. 89. LRRFS PFS vs TVRR
  90. 90. Clinical Implications• TVRR during adaptive RT has prognostic value!• It may serve as predictor that enable individualizedtherapeutic modification during RT:– Escalation of total radiation dose– Intensification of chemotherapy during and/or afterplanned RT– Early implementation of surgical salvage
  91. 91. Summary?orConfusion?
  92. 92. Definition of Anatomic Subsites• Neither clear demarcation line nor landmarkstructure is used:– No septum, capsule, fascia, mesothelial lining.– Anatomic boudaries are mostly arbitrarily chosenvisual landmarks for physicians’ convenience.• Overriding and/or skipped lesions are veryfrequent.
  93. 93. Extent of Local Treatment• One should understand Dx modality:– Principles of image acquisition and interpretation– Image resolution– False (+)/(-), (+)/(-) predictive value, overall accuracy• Extent of local Tx should depend on integratedinformation:– Physical findings: inspection, palpation, function test– Imaging findings: CT, MR, PET/CT, USG
  94. 94. Understand Various Uncertainties!• Simulation:– Posture, mouth opening, neck extension– Immobilization device– Contrast enhancement– Slice interval, thickness, region of interest– Available reference images (CT, MR, PET, USG)– Image co-registration (MR, PET)• Q: Are Dx CT and sim CT images are the same?• A: Never!
  95. 95. Understand Various Uncertainties!• All that is yellow is not always gold!– Too many noises interfering contrast enhancement– SUV = specific uptake value or silly useless value?• Great degree of variations:– Inter-personal (사람마다 달라요~~~)– Intra-personal (그때 그때 달라요~~~)• Why & how to put margins?
  96. 96. Motion Monitoring During Tomotherapy왜 이러는 걸까요?Motion overlap
  97. 97. Develop Your Own Protocol• Target delineation is game of probability:– P of oncologist (range) vs P of patient (all or none).– Everything is possible!– Nothing is impossible!• First refer to existing guidelines, protocols,policies, experienced seniors, expert opinions…• Practice game of trade-off:– Local cure vs complication, cost, time.• Develop reasonable and consistent protocol!
  98. 98. 論語 爲政 15章• 學而不思則罔 (학이불사즉망)– 학문을 닦아도 마음에 생각하는 바가 없으면사물의 이치를 환히 깨닫지 못함.• 思而不學則殆 (사이불학즉태)– 생각만 하고 더 배우지 않으면 독단에 빠져 위태롭게 됨.• 배우면 생각하고, 생각하며 일하라.
  99. 99. Baseline understandingPrinciple developmentExercise & PracticeRe-evaluationStudy Think
  100. 100. Study ThinkBaseline understandingExercise & PracticeRe-evaluationPrinciple developmentUpdated understandingPrinciple modificationEvidence-based Evidence-making
  101. 101. Therapeutic Ratio% tumor control by therapy A vs therapy BTherapeutic Gain Factor (TGF) =% complications by therapy A vs therapy B
  102. 102. Often times, it is very difficult to tellwhere the seashore exactly is…
  103. 103. Any Questions?Feel free to e-mail me atahnyc@skku.eduycahn.ahn@samsung.comyber55@naver.comyber55@gmail.com