Modern Techniques

8/2/2019 Modern Techniques

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Mohammad M. Gab-Allah


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SupraglottisSupraglottisTT11 Tumor is limited to oneone subsitesubsite of the supraglottis, withwith normalnormal vocalvocal cordcord mobilitymobility..

TT22 Tumor invades mucosa of moremore thanthan oneone adjacentadjacent subsitesubsite of the supraglottis orglottis or region outside the supraglottis (e.g., mucosa of base of tongue, vallecula,

medial wall of pyriform sinus), withoutwithout fixationfixation ofof thethe larynxlarynx..

TT33 Tumor is limitedlimited toto thethe larynxlarynx withwith vocalvocal cordcord fixationfixation and/orand/or invades any of thefollowing: postcricoid postcricoid areaarea,, prepre--epiglotticepiglottic tissuestissues,, paraglotticparaglottic spacespace, and/orand/or minorthyroid cartilage erosion (e.g., inner cortex).

TT44aa Tumor invades throughthrough thethe thyroidthyroid cartilagecartilage and/orand/or invades tissuestissues beyondbeyond thethelarynxlarynx (e.g., trachea, soft tissues of neck, including deep extrinsic muscle of thetongue, strap muscles, thyroid, or esophagus).

TT44bb Tumor invades prevertebral prevertebral spacespace,, encasesencases thethe carotidcarotid arteryartery, or invadesmediastinalmediastinal structuresstructures.


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GlottisGlottisTT11 Tumor is limitedlimited toto thethe vocalvocal cords(s)cords(s) (may involve anterior or posterior

commissure), with normal mobility.

TT11aa Tumor is limited to one vocal cord.

TT11bb Tumor involves both vocal cords.

TT22 Tumor extends to the supraglottissupraglottis and/orand/orsubglottissubglottis, and/orand/orwith impairedimpaired vocalvocal cordcordmobilitymobility..

TT33 Tumor is limitedlimited toto thethe larynxlarynx with vocalvocal cordcord fixationfixation and/orand/or invades paraglotticparaglotticspacespace, and or minor thyroid cartilage erosion (e.g., innerinner cortexcortex).

TT44aa Tumor invades through the thyroid cartilage and/orand/or invades tissues beyondbeyond thethelarynxlarynx (e.g., trachea, soft tissues of the neck, including deep extrinsic muscle of thetongue, strap muscles, thyroid, or esophagus).

TT44bb Tumor invades prevertebral space, encases the carotid artery, or invades mediastinalmediastinal

structuresstructures.


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SubglottisSubglottisTT11 Tumor is limitedlimited toto thethe subglottissubglottis..

TT22 Tumor extends to the vocalvocal cord(scord(s), withwith normalnormal oror impairedimpaired

mobilitymobility.

TT33 Tumor is limitedlimited toto thethe larynxlarynx, withwith vocal cord fixation.

TT44aa Tumor invades cricoidcricoid oror thyroidthyroid cartilagecartilage and/orand/or invadesinvades tissuestissues

beyondbeyond thethe larynxlarynx (e.g., trachea, soft tissues of neck, includingdeep extrinsic muscles of the tongue, strap muscles,thyroid, oresophagus).

TT44bb Tumor invades prevertebralprevertebral spacespace, encasesencases thethe carotidcarotid arteryartery, or

invades mediastinalmediastinal structuresstructures..


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Biopsy (Gold standard)

Vital dyes: toludine blue, methylene blue + contact endoscopy (91%sensitive, 52% specific)

5 Aminolevulenic Acid (5-ALA) nebulizer + short wave visible light(95% sensitive, 80% specific)

AdvantagesAdvantages::1. Office based.

2. No disturbance of the anatomy.

3. In experienced hands can detect the smallest lesions.

DisadvantageDisadvantage::1. Demanding technique.

2. No specimen.

3. Limited subsuface detection 150-200 only.

4. Not reliable in scarring, inflammation (false +ve), and hyperkeratosis (false ve)

OpticalO ptical coherencecoherence tomographytomography:: uses near infrared light waves toproduce cross-sectional images in vivo, with resolution like that ofhistology to detect epithelial and subepithelial lesions


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Severe Dysplasia/Carcinoma In Situ (CIS)Severe Dysplasia/Carcinoma In Situ (CIS)

Early Glottic and Cancer (T1/2,N0)Early Glottic and Cancer (T1/2,N0)

Early Supraglottic Cancer (T1/2)Early Supraglottic Cancer (T1/2)

Advanced Laryngeal Cancer (T3/4Advanced Laryngeal Cancer (T3/4-- any T,N+)any T,N+)


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Treatment vs. Observation?Treatment vs. Observation?

Laserexcision via endoscopeLaserexcision via endoscopeStripping of VC???Stripping of VC???

RadiotherapyRadiotherapy

Office based treatmentOffice based treatment

Chemoprevention of Laryngeal CancerChemoprevention of Laryngeal Cancer


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EndoscopicLaserexcisionEndoscopicLaserexcision

RadiotherapyRadiotherapy

Vertical partialVertical partial laryngectomylaryngectomy

SupracricoidSupracricoid laryngectomylaryngectomy


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Radiation.

Supra glottic laryngectomy

Laser

Supra cricoid laryngectomy


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Total laryngectomy +/- RT

Neck dissection if indicated

Chemoradiation

Laser


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Used in early glottic lesions (Tis, T1-T2/N0)

Some centers recommend in early supraglottic lesions (T1 and smallexophytic T2, unfit pt.)

Same rate of local control as surgery.

Superior in voice preservation ???Now recommended for more diffuse early lesions like T1b.

Not preferred in T2 glottic lesions with impaired VC mobility.

DisadvantagesDisadvantages:

1. Multiple sessions over weeks

2. Used once and recurrence is salvaged by Total Laryngectomy3. Complications (Mucositis, Odynophagia, Laryngeal edema,

Xerostomia, Stricture and fibrosis, Radionecrosis, Hypothyroidism)

DoseDose ofof radiationradiation:: Radiation doses ranges from 60 to 70 Gyadministered in 2-Gy fractions over54 days


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NewNew RTRT regimensregimens nownow leanlean towardstowards AlteredAltered fractionationfractionation

schedulesschedules:: HyperfractionationHyperfractionation andand hyperfractionationhyperfractionation ++

AccelerationAcceleration

HyperfractionationHyperfractionation:: allowsallows lowerlower fractionfraction dosedose ((11..11--11..22 Gy)Gy)

withwith multiplemultiple dailydaily dosesdoses ofof aa totaltotal dosedose rangerange betbet.. 7474--8080 GyGy,,

itit showedshowed betterbetter locoregionallocoregional controlcontrol andand lessless toxicitytoxicity

ContinuousContinuous hyperfractionatedhyperfractionated acceleratedaccelerated RTRT (CHART)(CHART)::

multiplemultiple fractions/dayfractions/day overover1212 daysdays showedshowed eveneven betterbetter locallocal

controlcontrol ratesrates asas itit preventsprevents tumortumor repopulationrepopulation butbut withwith higherhigher

toxicitytoxicity


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Combination of chemotherapy (CT) and RT has the followingeffects:

1.1. Additive effect:Additive effect: CTeradicates micrometastasis.

Spatial cooperation: independent activity of each ttt modality (RT inthe field and CT in and out the field).

2.2. Synergistic effect:Synergistic effect: CT agent interfere with DNA repair after sublethal dose (cisplatin)

Reducerepopulation of tumorcells by enhancingcytotoxic effect.

Reduce hypoxia makingcells moreradiosensitive via reducinginterstitial pressure or vice versa, as hypoxia may activate the agent(mitomycin)

Agent kills radioresistant cells inS phase (hydroxyurea) andsynchronizecells to G2/mitosis phase (paclitaxil)


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NeoadjuvantNeoadjuvant or Induction CRTor Induction CRT

Concurrent CRT (Concurrent CRT (ChemoradChemorad))

Induction Chemotherapy Followed byInduction Chemotherapy Followed by ChemoradChemorad(underrandomized trials)(underrandomized trials)


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administration of CT followed by RT (or surgery)alone.

bettercompliance. (lessercomplications)

Higher doses of CT drugs can begiven, with fewerunplanned delays and dosereductions.

Multiple agents may beused over multiplecycles as

compared to concurrent CRT. Cite the potential for tumors to progress during CT,

making it more difficult to obtain local control withcurative modalities such as RT or surgery.


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Published in 1991.

this trial randomized patients with stage III orIV larynx cancer to either:

(a) three cycles of neoadjuvant CT with cisplatin and5-FU followed b y definitive RT

(b) laryngectomy followed by postoperative RT.

This trial showed:A. equivalent 2-year survival (68%) between the

nonsurgical and surgical arms.

B. trial did not appropriately test the role of neoadjuvantCT, as the study did not include an RT alone arm.


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2 cycles of CT:2 cycles of CT:

CisplatinCisplatin: 100 mg/m/3wks

5FU5FU: 600 mg/m/3wks

+/-

DocitaxilDocitaxil: 15 mg/m/wk

ResponeRespone ( 50%)( 50%)

33rdrd cycle CT then RTcycle CT then RT

No responseNo response

Salvage total + post op RTSalvage total + post op RT


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Superior to induction CRT in locoregional controlrates.

Higher rate of toxcity.

Cisplatin-based CT regimens have been used inall concurrent CRT protocols. Can be delivered a s a s ingle agent in full dose with RT

it adds relatively little to stomatitis and radiation

mucositis, compared to other agents. Trails are based one fractionation of both RT and

CT cycles to achieve the best results with leasttoxcity.


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Three-arm trial randomized patients with advanced laryngealcancer to either:

1. RT alone

2. Neoadjuvant cisplatin and 5-FU followed by RT

3. Concurrent cisplatin and RT.

ResultsResults:: An update of this trial was presented in 2006 A t 5 years:1. Both concurrent cisplatin/RT and induction CT followed by RT had

superior laryngectomy-free survival (47% and 45%, respectively)

compared to RT alone (34%).2. Concurrent cisplatin and RT had superior locoregional control (69%)

compared to neoadjuvant CRT followed by RT (55%) or RT alone(51%).

3. Overall survival at 5 years was statistically similar between all threearms at approximately 55%.


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This includes the treatment of premalignant lesions usingphotodynamic therapy (PDT) and fiber-based laser systemse.g. the pulsed dye laser (PDL) and the pulsed KTP laser.

1)1) FiberFiber--basedbased laserlaser systemssystems:: The 585nm PDL and 532nm pulsed KTP lasers are the two most

widely used lasers for the in-office treatment.

The energy from these lasers is preferentially absorbed byoxyhemoglobin, with the absorption of energy from the pulsed KTP

being superior to that ofP

DL.

Effect: causing photoangiolysis of the sublesional blood vessels.Preferential destruction of intraepithelial desmosome junctions andseparation of the treated epithelial cells from the basementmembrane.


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PDLPDL

585 nm wavelength

Angiolytic

P

referentially absorbed by hemoglobin Microvascular Microvascular specific property

Relative tissue tissue-sparing.

It can beused with local 5-ALA inPDT

Pulsed KTPPulsed KTP 532 nm wavelength

Angiolytic and hemostatic

Preferentially absorbed by oxyhemoglobin

Greater affinity thanPDL


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FiberFiber-- based laser cont.based laser cont.

Advantages:Advantages:1. Avoidance of general anesthesia

2. Lowercost3. Improved efficiency

4. Minimal scarring

5. Treatment of bil. lesions and ant. commissure withminimal risk of web formation.

Disadvantages:Disadvantages:1. No specimen.

2. Poor lesionexposure.

3. Poor patient tolerance.


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PhotodynamicPhotodynamic therapytherapy:: Uses nontoxic chemicals that are taken up preferentially by dysplastic or

malignant cells.

These photoreactive chemicals are activated by light of a specific freq.Range unique to the compound used.

The light activation of tissues at the target site in the presence of oxygenresults in cell death that is confined to the cells that have selectivelyaccumulated the chemical.

PhotosensitizingPhotosensitizing agentsagents::

5-ALA.

Photofrin

Hematoporphyrin derivative

Foscan (temoporfin)

Used in ttt of benign laryngeal lesions like multiple papillomatosis.


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PDTPDT contcont..

AdvantagesAdvantages::

1. Office based

2. repeatable.3. The effects on voice quality are minimal,

4. scarring of the vocal folds has not been observed.

DisadvantageDisadvantage::

Careful light-avoiding precautions are required up to4 wks.

No pathologic specimen


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Chemoprevention is the use of specific chemical agents to reverse, suppress, or preventcarcinogenesis before invasive cancer develops

A number of agents show potential as chemopreventive agents for head and neck cancers

including green tea polyphenols, sulindac, COX II inhibitors, curcumin, and protease

inhibitors.

In numerous studies a low -fat diet and an increase in the consumption of fruits,

vegetables, and fiber were associated with a protective effect against a number of cancers.

13-cis-retinoic acid (13-cRA) has been studied extensively in oral leukoplakia.

A multiagent trial using 13-cRA, alpha tocopherol, and interferon- was conducted in

laryngeal lesions.

A complete remission was observed in 50% (7/14) of laryngeal lesions at 12 months.


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