Management of oral cavity cancers

1. Management of OralManagement of Oral
CancersCancers
Dr. Kandra PrasanthDr. Kandra Prasanth
Consultant Radiation OncologistConsultant Radiation Oncologist
Surya Global Hospitals.Surya Global Hospitals.

2. Radiation OncologyRadiation Oncology
 Radiation oncology is a branch of medicine thatRadiation oncology is a branch of medicine that
treats cancer by using high-energy radiation intreats cancer by using high-energy radiation in
the form of photons (i.e. X-rays & gamma rays)the form of photons (i.e. X-rays & gamma rays)
or subatomic particles (electrons or protons)or subatomic particles (electrons or protons)

3. IntroductionIntroduction
 Basics of Radiation TherapyBasics of Radiation Therapy
 Ionizing Radiation – X /Ionizing Radiation – X / γγ RaysRays
 Interaction of Radiation with matterInteraction of Radiation with matter
Transmission Attenuation
Scatter Absorption
Rad / Grey / cGy

4. Cancer Cell & Ionizing RadiationCancer Cell & Ionizing Radiation
 DNADNA is primary targetis primary target
 Double Strand breaks – Primary requisiteDouble Strand breaks – Primary requisite
 Reproductive Cell DeathReproductive Cell Death

5. RT is a Double Edge SwordRT is a Double Edge Sword

6. ↑↑ RT DoseRT Dose ↓↓ RT DoseRT Dose
↑↑ T – ControlT – Control ↓↓ T – ControlT – Control
↑↑ Normal TissueNormal Tissue
ToxicititesToxicitites
↓↓ Normal TissueNormal Tissue
ToxicititesToxicitites

7. TeletherapyTeletherapy
 TelecobaltTelecobalt
 Linear AcceleratorLinear Accelerator
 Simple TeletherapySimple Teletherapy
 SRS/SRTSRS/SRT
 3DCRT3DCRT
 IMRTIMRT
 IGRTIGRT
 Rapid ArcRapid Arc
 True BeamTrue Beam
 Gamma KnifeGamma Knife
 TomotherapyTomotherapy
 Cyber KnifeCyber Knife
BrachytherapyBrachytherapy
 IntracavitoryIntracavitory
 InterstitalInterstital
 MouldMould
 Pre Loaded /Pre Loaded /
AfterloadingAfterloading
 Manual / RemoteManual / Remote
 LDR / HDRLDR / HDR

8. Kilovoltage X-Ray 1920Kilovoltage X-Ray 1920

9. Telecobalt 1970sTelecobalt 1970s

10. Linear AcceleratorLinear Accelerator

11. True BeamTrue Beam

12. BrachytherapyBrachytherapy

13. What is Oral cancer..?What is Oral cancer..?
 Cancer that starts in the mouth isCancer that starts in the mouth is oral cavityoral cavity
cancercancer
 Includes lipsIncludes lips
 Inside lining of cheeks (buccal mucosa)Inside lining of cheeks (buccal mucosa)
 Gingiva (gums)Gingiva (gums)
 Floor of the mouthFloor of the mouth
 Anterior 2/3rds of the tongueAnterior 2/3rds of the tongue
 Hard palateHard palate

14. Neck NodeNeck Node
LevelsLevels

15. CT-PetCT-Pet
AnatomyAnatomy

16. 2002 American Joint Committee on Cancer (AJCC) TNM Staging System for the Lip and Oral Cavity
Tx; Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in Situ
T1: Tumor 2 cm or less in greatest dimension
T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension
T3: Tumor more than 4 cm in greatest dimension
T4 (lip): Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or skin of face (ie, chin or nose)
T4a: (oral cavity) Tumor invades adjacent structures (eg, through cortical bone, into deep [extrinsic] muscle of tongue
[genioglossus, hyoglossus, palatoglossus, and styloglossus], maxillary sinus, skin of face)
T4b: Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery
NX: Regional nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension
N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple
ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more
than 6 cm in greatest dimension
N2a: Metastasis in single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension
N2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension
N2c: Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
N3: Metastasis in a lymph node more than 6 cm in greatest dimension
Stage 0: Tis N0 M0
Stage I: T1 N0 M0
Stage II: T2 N0 M0
Stage III: T3 N0 M0, T1 N1 M0, T2 N1 M0, T3 N1 M0
Stage IVA: T4a N0 M0, T4a N1 M0, T1 N2 M0, T2 N2 M0, T3 N2 M0, T4a N2 M0
Stage IVB: Any T N3 M0, T4b Any N M0
Stage IVC: Any T Any N M1

18. Major Risk Factors for OralMajor Risk Factors for Oral
Cancer are:Cancer are:
 Tobacco use - 90%
 Alcohol use - 75-80%
 Age over 40
 UV – exposure – 30%
association with lip
cancer.

19.  HPV – 20 – 30% associationHPV – 20 – 30% association
 HSVHSV
 Nutritional deficiencies (Vit.A)Nutritional deficiencies (Vit.A)
 Oral lichen planusOral lichen planus
 Immuno- SupressionImmuno- Supression
 SyphilisSyphilis
 Marijuana useMarijuana use
 Chronic irritation (ill-fitted dentures, broken tooth)Chronic irritation (ill-fitted dentures, broken tooth)
 Chronic candidiasisChronic candidiasis
 P53 gene mutation (under study)P53 gene mutation (under study)
Additional Risk Factors LinkedAdditional Risk Factors Linked
To Oral Cancer Include:To Oral Cancer Include:

20. TobaccoTobacco
 Approx. 90% of oral cancers in SEARs are linked toApprox. 90% of oral cancers in SEARs are linked to
tobacco smoking or chewing.tobacco smoking or chewing.
 The risk of oral cancer increases with the :The risk of oral cancer increases with the : amountamount
andand durationduration both.both.
 Smokers haveSmokers have 6 times6 times greater risk of developing oralgreater risk of developing oral
cancer than nonsmokers.cancer than nonsmokers.
 Tobacco users who regularlyTobacco users who regularly use alcoholuse alcohol are atare at
greatest riskgreatest risk..
 All tobacco types are associated with oral cancer, forAll tobacco types are associated with oral cancer, for
example: cigarettes / cigars / pipes / snuff / chew /example: cigarettes / cigars / pipes / snuff / chew /
quidquid..

21.  Indigenous forms of smoking are : bidi, chuttaIndigenous forms of smoking are : bidi, chutta
((epidermoid Ca of hard palate - Andhra Pradeshepidermoid Ca of hard palate - Andhra Pradesh),),
chilam, hookah. It can also be inhaled as snuff.chilam, hookah. It can also be inhaled as snuff.
 Most common form of tobacco chewing in India isMost common form of tobacco chewing in India is
betal quid : betal leaf, arecanut, lime & tobacco (betal quid : betal leaf, arecanut, lime & tobacco (3636
times higher in non chewerstimes higher in non chewers).).
 It is common for the poor people to rub with thumbIt is common for the poor people to rub with thumb
– flakes of sun dried tobacco and slaked lime to form– flakes of sun dried tobacco and slaked lime to form
a mixture (khaini), which is then put in mouth ata mixture (khaini), which is then put in mouth at
frequent intervals during the day.frequent intervals during the day.

22. Relationship Between Cell EventsRelationship Between Cell Events

23. RT in Oral CancerRT in Oral Cancer
Management:Management:
 Treatment OutcomeTreatment Outcome
 CosmesisCosmesis
 Organ Preservation & FunctionOrgan Preservation & Function
 AgeAge
 Quality of lifeQuality of life

24. RTRT
 Radical RTRadical RT
 RT:RT:
 Conventional (7-8 weeks)Conventional (7-8 weeks)
 Hyperfractionation (5-6 weeks)Hyperfractionation (5-6 weeks)
 Hypofractionation (1-2 Gap 1-2 weeks)Hypofractionation (1-2 Gap 1-2 weeks)
 Pre Operative RTPre Operative RT (2-5 weeks)(2-5 weeks)
 Post Operative RTPost Operative RT (5-7 weeks)(5-7 weeks)
 Palliative RTPalliative RT
 Short CourseShort Course (1-2 weeks)(1-2 weeks)

25. RT CombinationsRT Combinations
 RT aloneRT alone
 Photons alonePhotons alone
 Photons + ElectronsPhotons + Electrons
 RTRT ++ Radiation Sensitizers (Chemotherapy)Radiation Sensitizers (Chemotherapy)
 RTRT ++ Radiation Protectors (Amifostine)Radiation Protectors (Amifostine)
 RTRT ++ BrachytherapyBrachytherapy
 Brachytherapy aloneBrachytherapy alone
 Brachy typeBrachy type
 Single plane implantSingle plane implant
 Double plane implantDouble plane implant
 Volume implantsVolume implants

26. Treatment options for head andTreatment options for head and
neck cancerneck cancer
 Early stages: surgery orEarly stages: surgery or radiationradiation
 Advanced stage:Advanced stage: chemoradiationchemoradiation oror
surgery followed by radiation andsurgery followed by radiation and
chemotherapychemotherapy
 Very advanced cases: radiation andVery advanced cases: radiation and
chemotherapychemotherapy

27. Indications for RT in Oral CaIndications for RT in Oral Ca
 Radical RTRadical RT
 T1, T2, T3, T4aT1, T2, T3, T4a
 Unresectable (Altered Fractionation HF/CB or RT + Radiation Sensitizer)Unresectable (Altered Fractionation HF/CB or RT + Radiation Sensitizer)
 elderly, frail, comorbid conditionselderly, frail, comorbid conditions
 refusal for surgeryrefusal for surgery
 prohibitive morbidity due to surgeryprohibitive morbidity due to surgery
 Pre OP RT :Pre OP RT : potentially inoperablepotentially inoperable
 Post OP RT :Post OP RT : (RT + Radiation Sensitizer)(RT + Radiation Sensitizer)
 pT3/4pT3/4
 Close & +ve marginClose & +ve margin
 Multiple nodesMultiple nodes
 Perineural invasionPerineural invasion
 Lympho vascular space invasionLympho vascular space invasion
 Extra Capsular extensionExtra Capsular extension
 Level IV – V nodesLevel IV – V nodes

28. RADIOTHERAPY DOSERADIOTHERAPY DOSE
1. External :1. External :
a. Alone : 7000 cGy to 7600 cGy /6-8 wks.a. Alone : 7000 cGy to 7600 cGy /6-8 wks.
(microscopic - 4600 - 5000(microscopic - 4600 - 5000
cGy)cGy)
b. Pre-op. : 46-50 Gy/ 4 1/2 - 5 1/2 wks.b. Pre-op. : 46-50 Gy/ 4 1/2 - 5 1/2 wks.
c. Post-op.: 60-66 Gy/ 6-7 wks.c. Post-op.: 60-66 Gy/ 6-7 wks.
2. Brachytherapy :2. Brachytherapy :
a. Alone : 6000 - 7000 cGy in 6 to 7 days.a. Alone : 6000 - 7000 cGy in 6 to 7 days.
b. External + Brachytherapyb. External + Brachytherapy
Ext : 46-50 Gy in 4 1/2 - 5 1/2 wks.Ext : 46-50 Gy in 4 1/2 - 5 1/2 wks.
++
Brachy : 2000-3000 cGy in 2-3 daysBrachy : 2000-3000 cGy in 2-3 days

29. pre- radiotherapy Dental Prophylaxispre- radiotherapy Dental Prophylaxis
ExtractionExtraction
 Caries (non-restorable)Caries (non-restorable)
 Active periapical disease (symptomatic teeth)Active periapical disease (symptomatic teeth)
 Moderate to severe periodontal diseaseModerate to severe periodontal disease
 Lack of opposing teeth, compromised hygieneLack of opposing teeth, compromised hygiene
 Partial impaction or incomplete eruptionPartial impaction or incomplete eruption
 Extensive periapical lesions (if not chronic or wellExtensive periapical lesions (if not chronic or well
localized)localized)
Start RT after 10 – 14 daysStart RT after 10 – 14 days

30. RT TechniquesRT Techniques
 Conventional 2DConventional 2D
 3DCRT / IMRT3DCRT / IMRT

31. Mould RoomMould Room
 Patient postioning :Patient postioning :
 SupineSupine
 Neck – Extension / hyperflexionNeck – Extension / hyperflexion
 Immobilzation devisesImmobilzation devises
 Head restHead rest
 Bite blockBite block
 Tongue depressorTongue depressor
 ThermoplasticsThermoplastics

32. SimulationSimulation
A face mask is usually made to hold the head
still and allow the targeting markings to be
painted on the mask

33. CT images are then
imported into the
treatment planning
computer
CT scan is obtained at this timeCT scan is obtained at this time

34. Digitally Reconstructed Images: Some patients have
very short necks making the radiation targeting more
difficult

35. Normal structures are identified on the computer
generated images, as well as the cancer targets, more
advanced case with spread to the lymph nodes

36. Conventional 2D PlanningConventional 2D Planning

37. 3D/IMRT(Rapid arc)3D/IMRT(Rapid arc)

38. Laser setupLaser setup

39. Virtual SimulationVirtual Simulation
CT-based virtual simulationCT-based virtual simulation
 use a full 3D image datasetuse a full 3D image dataset
 software toolssoftware tools
 external laser system for markingexternal laser system for marking
radiation therapy targetsradiation therapy targets

41. CONTOURINGCONTOURING

42. FusionFusion
 MRIMRI
 PET CTPET CT
 AngioAngio
 othersothers

43. IMRT: FIELDIMRT: FIELD

44. Left Buccal MucosaLeft Buccal Mucosa

45. Floor Of MouthFloor Of Mouth

46. Ca PalateCa Palate

47. Postop Ca TonguePostop Ca Tongue

48. CA UvulaCA Uvula

49. CA TonsilCA Tonsil

50. Quick Response to Radiation combinedQuick Response to Radiation combined
with chemotherapy, Tonsil cancer gonewith chemotherapy, Tonsil cancer gone
by 2 ½ weeksby 2 ½ weeks

51. Same patient at 4 weeksSame patient at 4 weeks

52. Tongue Cancer Before and 3Tongue Cancer Before and 3
Months after RadiationMonths after Radiation

53. Side effects
will relate to
the size and
location of
the radiation
field and the
normal
structures that
are in the way
of the beam
Side EffectsSide Effects

54. Side effects of radiation are related to the structures that
are near the tumor, so the radiation can effect the teeth
(dental problems) throat (sore throat) and saliva glands
(dryness and changes in taste)

55. 1. Skin irritation
2. Dry Mouth and changes in taste
and possible problems with teeth
3. Sore throat and problems with
swallowing and dehydration and
possible need for a feeding tube
4. Pain management problems
5. Laryngitis
6. Fatigue
Short Term Side EffectsShort Term Side Effects

56. Radiation
Dermatitis
almost everyone
gets a sun burned
reaction in the face
or neck and creams
are required (like
Aquaphor and
Silvadene)

57. Side Effects of Radiation to the MouthSide Effects of Radiation to the Mouth

58. Same patient at three monthsSame patient at three months

59. Acute side effectsAcute side effects
 Skin – Hyper pigmentation, Dry and moistSkin – Hyper pigmentation, Dry and moist
desqumationdesqumation
 Mucosa- Mucositis G2/3Mucosa- Mucositis G2/3
 Pharynx – Odynophagia / dysphagiaPharynx – Odynophagia / dysphagia
 Larynx – hoarseness of voiceLarynx – hoarseness of voice
 Salivary - XerostomiaSalivary - Xerostomia

60. 1. The dryness may be permanent,
depending on the amount of saliva glands
in the field
2. Teeth may be vulnerable to decay, and
caution is need with future dental care to
avoid jaw bone problems (osteonecrosis)
3. Some patients have long term problems
with swallowing
4. Some patients have persistent hoarseness
5. Small risk of low thyroid hormones
6. Carotid stenosis
Long Term Side EffectsLong Term Side Effects

61. Long Term Side EffectsLong Term Side Effects
Dryness and
discoloration of
the roof of mouth
is common as is
problems with
teeth
Long term dental care is critical to avoid
osteoradionecrosis (damage to the jaw bone with
exposed bone, may require hyperbaric oxygen treatment
to heal)

62. IMRT and Side EffectsIMRT and Side Effects
Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck
cancer (PARSPORT): a phase 3 multicenter randomized controlled trial.
Lancet Oncol. 2011;12(2):127.
Xerostomia Conventional IMRT
12 months 74% 38%
24 months 83% 29%

63. 5 YR SURVIVAL5 YR SURVIVAL
STAGE 1STAGE 1 STAGE IISTAGE II STAGEIIISTAGEIII STAGEIVSTAGEIV T 3/4T 3/4
LipLip 90%90% <60-30%<60-30% 30%30%
Anterior TongueAnterior Tongue 69%69% 41%41% 25%25%
S+R - 35%S+R - 35%
15%15% 33-60%33-60%
Buccal MucosaBuccal Mucosa 77%77% 65%65% 27%27% 18%18% 33-67%33-67%
Floor of the MouthFloor of the Mouth 97%97% 72%72% 51%51% 20%20% 33-67%33-67%
Lower GingivaLower Gingiva
Retromolar TrigoneRetromolar Trigone 70%70% 50-30%50-30% 30%30% 30-50%30-50%
Upper GingivaUpper Gingiva
Hard PalateHard Palate 75%75% 46%46% 36%36% 115115

64. During radiotherapyDuring radiotherapy
 Maintenance of good oral hygiene Brushing 2 toMaintenance of good oral hygiene Brushing 2 to
4 times daily with soft-bristled brush; flossing4 times daily with soft-bristled brush; flossing
dailydaily
 Daily topical fluoride Custom trays, brush-onDaily topical fluoride Custom trays, brush-on
prescription-strength fluorideprescription-strength fluoride
 Frequent saline rinsesFrequent saline rinses
 Lip moisturizer (non-petroleum based)Lip moisturizer (non-petroleum based)
 Passive jaw-opening exercises to reduce trismusPassive jaw-opening exercises to reduce trismus

65. After radiotherapyAfter radiotherapy
 Complete dental work that was deferred duringComplete dental work that was deferred during
radiotherapyradiotherapy
 Maintain integrity of teeth Especially those inMaintain integrity of teeth Especially those in
radiation fieldsradiation fields
 Frequent follow-upFrequent follow-up

66. CHEMOTHERAPYCHEMOTHERAPY
 Alkylating Agents – Cisplatin, CarboplatinAlkylating Agents – Cisplatin, Carboplatin
 Antimetabolites – MethotrexateAntimetabolites – Methotrexate
 Antitumour Antibiotics – Bleomycin, MitomycinAntitumour Antibiotics – Bleomycin, Mitomycin
 Taxanes – Paclitaxel, Docetaxel.Taxanes – Paclitaxel, Docetaxel.

67. Neoadjuvant ChemotherapyNeoadjuvant Chemotherapy
 Use of chemotherapy prior to surgery orUse of chemotherapy prior to surgery or
Radiation Treatment.Radiation Treatment.
 Intent is to improve local and distant control ofIntent is to improve local and distant control of
disease in order to provide greater organdisease in order to provide greater organ
preservation and overall survival.preservation and overall survival.
 Neoadjuvant setting has advantage of drugNeoadjuvant setting has advantage of drug
delivary to the tumour with intact vasculature.delivary to the tumour with intact vasculature.

68. Neoadjuvant ChemotherapyNeoadjuvant Chemotherapy
 Common drug combinations used are CisplatinCommon drug combinations used are Cisplatin
and 5FU, Docetaxel + Cisplatin + 5FU.and 5FU, Docetaxel + Cisplatin + 5FU.
 Response rates is between 68 and 93 percent,Response rates is between 68 and 93 percent,
complete response is as high as 58 percent.complete response is as high as 58 percent.
 Must be followed with definitive treatment likeMust be followed with definitive treatment like
surgery or RT.surgery or RT.

69. CONCURRENT CHEMORTCONCURRENT CHEMORT
 Chemotherapy delivered during the course ofChemotherapy delivered during the course of
Radiation treatment.Radiation treatment.
 Commonly used regimens are single agentCommonly used regimens are single agent
Cisplatin(Delivered weekly schedule), CisplatinCisplatin(Delivered weekly schedule), Cisplatin
+ 5FU.+ 5FU.
 Intent is elimination of Micro metastases,Intent is elimination of Micro metastases,
Improved local control.Improved local control.

70. Palliative ChemotherapyPalliative Chemotherapy
 Intent is to Control the symptoms Like pain ,Intent is to Control the symptoms Like pain ,
Bleeding etcBleeding etc
 Used with single agent or combination.Used with single agent or combination.

71. ChemotherapyChemotherapy

72. EGFR(Epidermal Growth FactorEGFR(Epidermal Growth Factor
Receptor)Receptor)
 Cell surface growth regulator expressed by two-thirds of allCell surface growth regulator expressed by two-thirds of all
human cancer cellshuman cancer cells
 Upregulated in 98% of HNCUpregulated in 98% of HNC
 EGFR expression has prognostic significanceEGFR expression has prognostic significance
 (Ang 2002)(Ang 2002)

73. CetuximabCetuximab
 Recombinant human/mouse chimeric Monoclonal antibody vsRecombinant human/mouse chimeric Monoclonal antibody vs
EGFREGFR
 Binds EGFR, HER1, c-ErbB-1 on both normal and tumor cellsBinds EGFR, HER1, c-ErbB-1 on both normal and tumor cells
 Blocks EGF and other ligand bindingBlocks EGF and other ligand binding
 Binding to the EGFR blocks phosphorylation and activation ofBinding to the EGFR blocks phosphorylation and activation of
receptor-associated kinasesreceptor-associated kinases
 Inhibits cell growth, induction of apoptosis, and decreases matrixInhibits cell growth, induction of apoptosis, and decreases matrix
metalloproteinase and vascular endothelial growth factormetalloproteinase and vascular endothelial growth factor
production.production.

74. EGFREGFR

75. Randomized Trial XRT versus
XRT + Erbitux
Radiation plus Erbitux
Radiation
N Engl J Med 2006; 354:567-578

76. Follow-upFollow-up
 Clinical examination of head and neck mucosa (includingClinical examination of head and neck mucosa (including
fiberoptic ) and neck palpation / performance status /fiberoptic ) and neck palpation / performance status /
nutritional assessmentnutritional assessment
 every 2 months (first 2 years),every 2 months (first 2 years),
 every 6 months (years 3-5),every 6 months (years 3-5),
 once a year (> 5 year)once a year (> 5 year)
 Dental examination and orthopantomogram every 6 monthsDental examination and orthopantomogram every 6 months
 Chest X-ray every yearChest X-ray every year
 Chest spiral CT every yearChest spiral CT every year
 Laboratory tests: TSH every year (if Radiotherapydelivered)Laboratory tests: TSH every year (if Radiotherapydelivered)
 Evolution of late toxicity (EORTC/RTOG) scaleEvolution of late toxicity (EORTC/RTOG) scale

77. Salvage treatment for recurrentSalvage treatment for recurrent
diseasedisease
 Lip, mobile tongue, floor of mouth:Lip, mobile tongue, floor of mouth:
 T1 N0 :T1 N0 :
 BrachytherapyBrachytherapy
 SurgerySurgery
 Any other T, any other NAny other T, any other N
 Surgery + radical ND ± post-operative RxTh if not previouslySurgery + radical ND ± post-operative RxTh if not previously
delivereddelivered
 RxThRxTh
 Palliative carePalliative care
 Metastasis :Metastasis :
 Chemotherapy + best supportive careChemotherapy + best supportive care

79. Thank youThank you