Oral cavity ca

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Management of Oral Management of Oral Cancers Cancers Dr. Kandra Prasanth Dr. Kandra Prasanth Consultant Radiation Consultant Radiation Oncologist Oncologist Surya Global Hospitals. Surya Global Hospitals.

Transcript of Oral cavity ca

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Management of Management of Oral CancersOral Cancers

Dr. Kandra PrasanthDr. Kandra PrasanthConsultant Radiation OncologistConsultant Radiation Oncologist

Surya Global Hospitals.Surya Global Hospitals.

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Radiation OncologyRadiation Oncology Radiation oncology is a branch of Radiation oncology is a branch of

medicine that treats cancer by using medicine that treats cancer by using high-energy radiation in the form of high-energy radiation in the form of photons (i.e. X-rays & gamma rays) photons (i.e. X-rays & gamma rays) or subatomic particles (electrons or or subatomic particles (electrons or protons)protons)

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IntroductionIntroduction Basics of Radiation TherapyBasics of Radiation Therapy

Ionizing Radiation – X / Ionizing Radiation – X / γγ Rays Rays Interaction of Radiation with matterInteraction of Radiation with matter

Transmission

Attenuation

Scatter Absorption

Rad / Grey / cGy

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Cancer Cell & Ionizing Cancer Cell & Ionizing RadiationRadiation DNADNA is primary target is primary target

Double Strand breaks – Primary Double Strand breaks – Primary requisiterequisite

Reproductive Cell DeathReproductive Cell Death

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RT is a Double Edge RT is a Double Edge SwordSword

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↑ ↑ RT RT DoseDose

↓ ↓ RT DoseRT Dose

↑ ↑ T – ControlT – Control ↓ ↓ T – ControlT – Control↑ ↑ Normal Normal Tissue Tissue ToxicititesToxicitites

↓ ↓ Normal Normal Tissue Tissue ToxicititesToxicitites

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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 / HDR LDR / HDR

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Kilovoltage X-Ray 1920Kilovoltage X-Ray 1920

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Telecobalt 1970sTelecobalt 1970s

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Linear AcceleratorLinear Accelerator

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True BeamTrue Beam

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BrachytherapyBrachytherapy

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What is Oral cancer..?What is Oral cancer..? Cancer that starts in the mouth is Cancer that starts in the mouth is

oral cavityoral cavity cancer cancer 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

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Neck Node Neck Node LevelsLevels

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CT-Pet CT-Pet AnatomyAnatomy

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2002 American Joint Committee on Cancer (AJCC) TNM Staging System for the Lip and Oral CavityTx; Primary tumor cannot be assessedT0: No evidence of primary tumorTis: Carcinoma in SituT1: Tumor 2 cm or less in greatest dimensionT2: Tumor more than 2 cm but not more than 4 cm in greatest dimensionT3: Tumor more than 4 cm in greatest dimensionT4 (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 assessedN0: No regional lymph node metastasisN1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimensionN2: 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 dimensionN3: Metastasis in a lymph node more than 6 cm in greatest dimension

Stage 0: Tis N0 M0Stage I: T1 N0 M0Stage II: T2 N0 M0Stage III: T3 N0 M0, T1 N1 M0, T2 N1 M0, T3 N1 M0Stage IVA: T4a N0 M0, T4a N1 M0, T1 N2 M0, T2 N2 M0, T3 N2 M0, T4a N2 M0Stage IVB: Any T N3 M0, T4b Any N M0Stage IVC: Any T Any N M1

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Major Risk Factors for Major Risk Factors for Oral Cancer are:Oral Cancer are:

Tobacco use - 90%

Alcohol use - 75-80%

Age over 40

UV – exposure – 30% association with lip cancer.

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HPV – 20 – 30% associationHPV – 20 – 30% association HSVHSV Nutritional deficiencies (Vit.A)Nutritional deficiencies (Vit.A) Oral lichen planus Oral lichen planus Immuno- Supression Immuno- Supression SyphilisSyphilis Marijuana useMarijuana use Chronic irritation (ill-fitted dentures, Chronic irritation (ill-fitted dentures,

broken tooth)broken tooth) Chronic candidiasisChronic candidiasis P53 gene mutation (under study)P53 gene mutation (under study)

Additional Risk Factors Additional Risk Factors Linked To Oral Cancer Linked To Oral Cancer

Include:Include:

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TobaccoTobacco Approx. 90% of oral cancers in SEARs are Approx. 90% of oral cancers in SEARs are

linked to tobacco smoking or chewing.linked to tobacco smoking or chewing. The risk of oral cancer increases with the The risk of oral cancer increases with the

: : amount amount and and durationduration both. both. Smokers have Smokers have 6 times6 times greater risk of greater risk of

developing oral cancer than nonsmokers.developing oral cancer than nonsmokers. Tobacco users who regularly Tobacco users who regularly use alcoholuse alcohol

are at greatest riskare at greatest risk.. All tobacco types are associated with oral All tobacco types are associated with oral

cancer, for example: cigarettes / cigars / cancer, for example: cigarettes / cigars / pipes / snuff / chew / pipes / snuff / chew / quidquid..

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Indigenous forms of smoking are : bidi, Indigenous forms of smoking are : bidi, chutta (chutta (epidermoid Ca of hard palate - epidermoid Ca of hard palate - Andhra PradeshAndhra Pradesh), chilam, hookah. It can ), chilam, hookah. It can also be inhaled as snuff.also be inhaled as snuff.

Most common form of tobacco chewing in Most common form of tobacco chewing in India is betal quid : betal leaf, arecanut, India is betal quid : betal leaf, arecanut, lime & tobacco (lime & tobacco (36 times higher in non 36 times higher in non chewerschewers).).

It is common for the poor people to rub It is common for the poor people to rub with thumb – flakes of sun dried tobacco with thumb – flakes of sun dried tobacco and slaked lime to form a mixture (khaini), and slaked lime to form a mixture (khaini), which is then put in mouth at frequent which is then put in mouth at frequent intervals during the day.intervals during the day.

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Relationship Between Relationship Between Cell EventsCell Events

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

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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 RT Pre Operative RT (2-5 weeks)(2-5 weeks) Post Operative RT Post Operative RT (5-7 weeks)(5-7 weeks)

Palliative RTPalliative RT Short Course Short Course (1-2 weeks)(1-2 weeks)

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RT CombinationsRT Combinations RT aloneRT alone

Photons alonePhotons alone Photons + ElectronsPhotons + Electrons RT RT ++ Radiation Sensitizers (Chemotherapy) Radiation Sensitizers (Chemotherapy) RT RT ++ Radiation Protectors (Amifostine) Radiation Protectors (Amifostine)

RT RT ++ Brachytherapy Brachytherapy Brachytherapy aloneBrachytherapy alone

Brachy typeBrachy type Single plane implantSingle plane implant Double plane implantDouble plane implant Volume implantsVolume implants

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Treatment options for Treatment options for head and neck cancerhead and neck cancer Early stages: surgery or Early stages: surgery or radiationradiation Advanced stage: Advanced stage: chemoradiationchemoradiation or or

surgery followed by radiation and surgery followed by radiation and chemotherapychemotherapy

Very advanced cases: radiation and Very advanced cases: radiation and chemotherapychemotherapy

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Indications for RT in Indications for RT in Oral CaOral Ca

Radical RTRadical RT T1, T2, T3, T4a T1, T2, T3, T4a

Unresectable (Altered Fractionation HF/CB or RT + Unresectable (Altered Fractionation HF/CB or RT + Radiation Sensitizer)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

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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 cGy)(microscopic - 4600 - 5000 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 days Brachy : 2000-3000 cGy in 2-3 days

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pre- radiotherapy Dental pre- radiotherapy Dental ProphylaxisProphylaxis

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 Extensive periapical lesions (if not chronic or

well localized)well localized)Start RT after 10 – 14 daysStart RT after 10 – 14 days

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RT TechniquesRT Techniques

Conventional 2DConventional 2D 3DCRT / IMRT3DCRT / IMRT

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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

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SimulationSimulation

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

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CT images are then imported into the treatment planning computer

CT scan is obtained at this CT scan is obtained at this time time

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

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

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Conventional 2D Conventional 2D PlanningPlanning

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

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Laser setupLaser setup

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Virtual SimulationVirtual SimulationCT-based virtual simulation CT-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 markingradiation therapy targetsradiation therapy targets

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CONTOURINGCONTOURING

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FusionFusion MRIMRI PET CTPET CT AngioAngio othersothers

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IMRT: FIELDIMRT: FIELD

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Left Buccal MucosaLeft Buccal Mucosa

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Floor Of MouthFloor Of Mouth

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Ca PalateCa Palate

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Postop Ca TonguePostop Ca Tongue

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CA UvulaCA Uvula

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CA TonsilCA Tonsil

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Quick Response to Radiation Quick Response to Radiation combined with chemotherapy, combined with chemotherapy,

Tonsil cancer gone by 2 ½ Tonsil cancer gone by 2 ½ weeksweeks

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Same patient at 4 weeksSame patient at 4 weeks

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Tongue Cancer Before and Tongue Cancer Before and 3 Months after Radiation3 Months after Radiation

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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

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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)

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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

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

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Side Effects of Radiation to Side Effects of Radiation to the Mouththe Mouth

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Same patient at three Same patient at three monthsmonths

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Acute side effectsAcute side effects Skin – Hyper pigmentation, Dry and Skin – Hyper pigmentation, Dry and

moist desqumationmoist desqumation Mucosa- Mucositis G2/3Mucosa- Mucositis G2/3 Pharynx – Odynophagia / dysphagiaPharynx – Odynophagia / dysphagia Larynx – hoarseness of voiceLarynx – hoarseness of voice Salivary - XerostomiaSalivary - Xerostomia

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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

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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)

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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%

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5 YR SURVIVAL5 YR SURVIVALSTAGE 1STAGE 1 STAGE STAGE

IIIISTAGEIIISTAGEIII 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 Floor of the MouthMouth

97%97% 72%72% 51%51% 20%20% 33-67%33-67%

Lower GingivaLower Gingiva

Retromolar Retromolar TrigoneTrigone

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

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During radiotherapyDuring radiotherapy Maintenance of good oral hygiene Maintenance of good oral hygiene

Brushing 2 to 4 times daily with soft-Brushing 2 to 4 times daily with soft-bristled brush; flossing dailybristled brush; flossing daily

Daily topical fluoride Custom trays, Daily topical fluoride Custom trays, brush-on prescription-strength fluoridebrush-on prescription-strength fluoride

Frequent saline rinsesFrequent saline rinses Lip moisturizer (non-petroleum based)Lip moisturizer (non-petroleum based) Passive jaw-opening exercises to Passive jaw-opening exercises to

reduce trismusreduce trismus

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After radiotherapyAfter radiotherapy Complete dental work that was Complete dental work that was

deferred during radiotherapydeferred during radiotherapy Maintain integrity of teeth Especially Maintain integrity of teeth Especially

those in radiation fieldsthose in radiation fields Frequent follow-upFrequent follow-up

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CHEMOTHERAPYCHEMOTHERAPY Alkylating Agents – Cisplatin, Alkylating Agents – Cisplatin,

CarboplatinCarboplatin Antimetabolites – MethotrexateAntimetabolites – Methotrexate Antitumour Antibiotics – Bleomycin, Antitumour Antibiotics – Bleomycin,

MitomycinMitomycin Taxanes – Paclitaxel, Docetaxel.Taxanes – Paclitaxel, Docetaxel.

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Neoadjuvant Neoadjuvant ChemotherapyChemotherapy

Use of chemotherapy prior to surgery Use of chemotherapy prior to surgery or Radiation Treatment.or Radiation Treatment.

Intent is to improve local and distant Intent is to improve local and distant control of disease in order to provide control of disease in order to provide greater organ preservation and greater organ preservation and overall survival.overall survival.

Neoadjuvant setting has advantage of Neoadjuvant setting has advantage of drug delivary to the tumour with drug delivary to the tumour with intact vasculature.intact vasculature.

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Neoadjuvant Neoadjuvant ChemotherapyChemotherapy

Common drug combinations used Common drug combinations used are Cisplatin and 5FU, Docetaxel + are Cisplatin and 5FU, Docetaxel + Cisplatin + 5FU.Cisplatin + 5FU.

Response rates is between 68 and 93 Response rates is between 68 and 93 percent, complete response is as percent, complete response is as high as 58 percent.high as 58 percent.

Must be followed with definitive Must be followed with definitive treatment like surgery or RT.treatment like surgery or RT.

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CONCURRENT CONCURRENT CHEMORTCHEMORT

Chemotherapy delivered during the Chemotherapy delivered during the course of Radiation treatment.course of Radiation treatment.

Commonly used regimens are single Commonly used regimens are single agent Cisplatin(Delivered weekly agent Cisplatin(Delivered weekly schedule), Cisplatin + 5FU.schedule), Cisplatin + 5FU.

Intent is elimination of Micro Intent is elimination of Micro metastases, Improved local control.metastases, Improved local control.

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Palliative ChemotherapyPalliative Chemotherapy Intent is to Control the symptoms Intent is to Control the symptoms

Like pain , Bleeding etcLike pain , Bleeding etc Used with single agent or Used with single agent or

combination.combination.

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ChemotherapyChemotherapy

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EGFR(Epidermal Growth EGFR(Epidermal Growth Factor Receptor)Factor Receptor)

Cell surface growth regulator expressed by two-Cell surface growth regulator expressed by two-thirds of all human cancer cells thirds of all human cancer cells

Upregulated in 98% of HNCUpregulated in 98% of HNC EGFR expression has prognostic significanceEGFR expression has prognostic significance

(Ang 2002)(Ang 2002)

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CetuximabCetuximab Recombinant human/mouse chimeric Monoclonal Recombinant human/mouse chimeric Monoclonal

antibody vs EGFRantibody vs EGFR Binds EGFR, HER1, c-ErbB-1 on both normal and tumor Binds EGFR, HER1, c-ErbB-1 on both normal and tumor

cells cells Blocks EGF and other ligand bindingBlocks EGF and other ligand binding Binding to the EGFR blocks phosphorylation and Binding to the EGFR blocks phosphorylation and

activation of receptor-associated kinasesactivation of receptor-associated kinases Inhibits cell growth, induction of apoptosis, and Inhibits cell growth, induction of apoptosis, and

decreases matrix metalloproteinase and vascular decreases matrix metalloproteinase and vascular endothelial growth factor production.endothelial growth factor production.

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EGFREGFR

                                                                                          

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Randomized Trial XRT versus XRT + Erbitux

Radiation plus Erbitux

Radiation

N Engl J Med 2006; 354:567-578

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Follow-upFollow-up

Clinical examination of head and neck mucosa Clinical examination of head and neck mucosa (including fiberoptic ) and neck palpation / (including fiberoptic ) and neck palpation / performance status / nutritional assessmentperformance status / nutritional 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 Dental examination and orthopantomogram every 6

monthsmonths Chest X-ray every yearChest X-ray every year Chest spiral CT every yearChest spiral CT every year Laboratory tests: TSH every year (if Laboratory tests: TSH every year (if

Radiotherapydelivered)Radiotherapydelivered) Evolution of late toxicity (EORTC/RTOG) scaleEvolution of late toxicity (EORTC/RTOG) scale

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Salvage treatment for Salvage treatment for recurrent diseaserecurrent disease

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 Surgery + radical ND ± post-operative RxTh if not

previously deliveredpreviously delivered RxThRxTh

Palliative carePalliative care Metastasis :Metastasis :

Chemotherapy + best supportive careChemotherapy + best supportive care

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Thank youThank you