*supraglottic T1N0-small N1. most ofT2N0 M0 ////**T2N1-3M0/T3N0-3M0 ///***T4N0-3M0-1 this then divided to operable & inoperable
Canaer of larynx
CANCER OF LARYNX
the larynx is consists of a cartilaginous skeleton with ligaments,which carries the muscles and mostly is covered by mucous membrane . skeleton of the larynx ;-1)Thyroid cartilage ;- consist of tow lateral laminae which are fused in front (bow ship). At the tip of bow is a notch (Adam apple) . The superior and inferior horn arise from the posterior edge of each laminae2) Caricoid cartilage ;-it is ship is like signet ring .it is lamina is 2-2.5 cms lies posterior .the upper edage of the lamina has tow articular surface for the arytenoid cartilage .the lateral surface on each side has articular surface for the inferior horn of the thyriod cartilage .
Arytenoid cartilage ;-pair of cartilage sited on the upper edge of the lamina of the cricoid cartilage .it has the shap of triangular pyramid .The vocal cord are two thickened uppper end of the conus attached posterior to the vocal process of both arytenoids cartilage and interiorly to the inner surface of the angle of the thyroid cartilagecricoarytenoid muscles .Epiglottis ;-lies against the middle of the thyroid cartilage
Laryngeal ligaments ;-is a membrane composed of a dense elastic fiber net which lies below the mucous memberane of the larynx and has different sickness in different region (conus elasticus-vocal cord –median cricothyroid ligament l-quadrangular membrane –vestibular ligament …)
New case in 2009 is 12,290 with ca larynx .with men affected four time more than female .deaths from ca larynx is 3,660 . With modern care the deaths dropped from 2,97 per 100,000 to 2,24 per 100,000 .Risk factors ;-1) Age > 55 yrs .2)Gender male to female ratio 4:13)Cigarette smoking (2-25X increase)
4) Alcohol consumption (2-6 increase ) the .The combination of cigarette and alcohol ↑(40-100) .5) Race African –American are more affected .6) Past medical history of head and neck cancer ↑risk of ca larynx .7) Genetic factors ;- e.g fanconia anemia and dyskeratosis congenita (condation→aplastic anemia ↑ risk of ca larynx .8) Condition → ↓ immunity (AIDS –organ transplant ) .↑risk of ca larynx .
The majority of ca larynx which arise from the mucosal surface is squamous cell carcinoma .The most are well to mode differentiated . Ca larynx sub site percent supraglottic 35% glottic 65% subglottic 1%
spread occur by one of the three ;-A) Local extension ;- the most common ,spread to cartilages→ sclerosis then by additional growth causes cartilage erosion → destruction and penetration of cartilages .B) Lymph nodes met- Occur less common .the lymphatic drainage depend on the origin of the 1ry sites .C) Distant mets- ;-the most common site of hematogenous spread is the bones then less common to the lungs .
ipsilateral nodes contralateral nodes 11 111 1v v 1 11 111 1v v1supr1% 39% 26% 8% 5% O% 12% 5% 3% 3% lymph nodes involved in the ca larynx (supraglottic)
Clinical presentation ;-Early presentation is hoarseness of the voiceChange in the quality of the voice .While advance presentation is difficulty in the swallowing . Cervical adenopathy . Weight loss . Throat pain . Referred pain . Air way obstruction .Head and neck examination :- inspection of the scalp,ears,Nose, and mouth . Palpation of the neck, mouth, tongueMobility, base of the tongue, and floor of mouth.Endoscope to nasal cavity,nasopharynx,oropharynx,Hypopharynx and larynx . Carefully cranial nerve examination
Diagnosis and clinical staging depends on finding from history ,physical examination ,imaging and lab tests . Pathological staging depends on finding from surgical resection and histological examination .There are American joint committee on cancer (AJCC)And Tumor, Node, and Metastasis .(TNM)
AJCC ,TNM classification of carcinoma Primary tumor ;-Tx primary tumor can not be assessedT0 No evidence of primary tumorT is Carcinoma insitu
supraglottis ;-T1 Tumor limited to 1 sub site of supraglottis ,with normal vocal cord mobilityT2 Tumor in more than 1 adjacent sub site of the supraglottis or glottis .with out fixation of the larynxT3 tumor limited to larynx with vocal cord fixation, or invades following postcricoid area preepiglottic space Or inner cortex of thyroid cartilageT4a Moderate advanced local disease, tumor invade thyroid cartilage or pre -larynx tissuesT4b Very advanced local disease ,tumor invade prevertedral space,carotid artery,or invades mediastinal structure
GlottisT1 Tumor limited to 1 vocal cord with normal mobilityT1b Tumor involve both vocal cord with normal mobilityT2 Tumor extends to supraglottis or subglottis with impaired vocal cord mobility.T3 Tumor limited to the larynx with vocal cord fixation Or involve paraglottic space ,or inner cortex of thyroid cartilage .T4a Moderately advanced local disease ,outer cortex of thyroid cartilage or tissues surrounding the larynxT4b Very advanced local disease prevertebral space or mediastinal structures .
Sub glottis ;-T1 tumor limited to the subglottisT2 Tumor extend to vocal cord with normal or impaired mobilityT3 Tumor limited to the larynx with vocal cord fixationT4 Moderately advanced local disease .invading of the cricoid or thyroid cartilage or tissue around the larynx .T4b Very advanced local disease ,invading the prevertebral space ,cartoid artery ,meditational structure .
Regional lymph nodes ;-Nx Can not be assessedN0 no lymph nodes metastasisN1 metastasis in the ipsilateral lymph nodes≤3 cm (greater dimension)N2a Metastasis in single ipsilateral lymph nodes>3cm but≤6cm in greater dimensionN2b Metastasis in multiple ipsilateral lymph nodes none >6 cmN2c Metastasis in bilateral or contra lateral lymph nodes none > 6cmN3 Metastasis in lymph nodes >6cm in greater dimension
Ca larynx suspected Complete history & physical exam Endoscopy and biopsy imaging Lab interventi study study on Lesion Advanced Advancedincapable of LESION lesion lesion regional CAPABLE suitable for beyond met- OF organ organGLOTTIC T1- REGIONAL conservation conservation 2N0M0 *Mets- ** ***
The out come of treatment of ca larynx is varies substantially, from excellent to poor. The most important prognostic factors include extent/stage at diagnosis, the exact site of origin of disease and patient’s performance status /ability to tolerate the desired therapy
Localized lesion incapable of regional metastasis ; this include the SCC of glottis (T1 or T2, N0 ) .this treated by radiation therapy to the primary site only . Surgery is second option but radiation is preferable due to subsequent voice quality .Radiation therapy ;- is indicated for all early stage . The techniques ;- small opposed portals (e.g. 5x5 or 6x6 cm ) treating the primary tumor only .the dose is 63 Gy in 28 fr/ 2.25 CGY/day in 5.6 weeks .
Usually the portals extend from hyoid bone to the bottom of the cricoids cartilage (upper/lower) and from the flash of the skin to the anterior aspect of the vertebral body (anterior/posterior) .Usually we use tow parallel opposed 4-6 MV photonBeam field .In recent years arandomized study done concurring the fraction schaclat for T1N0M0 glottic cancer were treated either with 2,0 or 2.25 Gy ,the 5yrs local control rate favored the group that received 2.25 Gy
(92 versus 77%) . But the cause specific survival rate were similar (100 and 97%) .Localized lesion capable of regional metastasisLimited extent SCC of the supraglottic larynx(T1N0-smallN1 and most T2N0 . In treatment of the these type of the lesion the tow type of the treatment can be done radiation and surgery but the radiation is preferable due to less morbid .Radiation ;- suitable for all case . Specially if the extend of the disease required total laryngectomy to repair the surgery .
The techniques ;-For small supraglottic include the primary lesion pulse the upper and mid cervical (level1&11) .For more extensive supraglottic lesion also include low, anterior cervical (level1v) nodes .If N1 anterior cervical disease the posterior cervical (level 5) should be treated .Radiation technique ;-usually lateral and parallels op-Posed fields are used . For T1 supraglottic lesion a dose of66 GY in 33fr 2fr/day .for T2 supraglottic 70 GY in35 fr .
Advanced lesion suitable for organ preservationT3 –T4 ;- this lesion traditionally treated by laryngectomy(with or without pharyngectomy) .now these is larynx sparing therapy these is no deferent in the cervival between surgery and the larynx sparing therapy .but not all lesion are suitable for organ preservation therapy (unreliable patients,pts contuse smoking during treatment ,hypertensive,pts who cannot tolerate discomfort of the surgery)
The treatment modal which used for organ preservation;-Indicated for advanced lesion that have not penetrated cartilage .(cord fixation is not contra-Indication).Techniques ;-the primary tumor and clinical involvedNodes should receive 70 GY in 35 frs .All anterior and posterior cervical andsupraclavicular clinically uninvolved are at risk for sub clinical involvement and need to receive minimum of 50 GY
The chemotherapy ;- include cisplatin I.V on day 1,22 &43 of radiotherapy . Clinical evidence ;- Randomized trials ;-Departmen pts number= 332 ( stage 111 or 1v ca larynx ). Median fallow up 33t of veteran monthsaffairs Compared 3 cycles of indication cisplatin + flurouracil chemotherapylarynx Versus laryngectomy postoperative radiation. The survival rate is equal in both arm for 2 yrs =68% ( p=0.098) .there were More local recurrence (p=0.005)and fewer distant metastases (p=0.016) In the chemotherapy group than in the other group
EORTC2489 Randomized of patent number202 with ca1b larynx of the pyriform sinus stage 11-1v follow up to 51 months . Compared cycles of inducation cisplatin chemotherapy and thenradiotherapy verus larngectomy and postoperative radiotherapy median cervival was 44months in inducation chemotherapy arm and 25 months in surgery arm . Local and regional recurrence was similar in both arm
RTOG Randomized care of 520 patients who wise Required laryngectomy . Comparing inducation cisplatin plus fluoro- Uracil and then radiotherapy versus radiotherapy with concurrent administration of cisplatin versus radiotherapy alone . The primary end point of preservation of the larynx significantly favored concurrent Therapy 2yrs-88% while inducation chemo- 75% and the radiotherapy 70%. 2nd end point of loco regional control significantly Favored concurrent therapy 78% while with inducation chemo-61% and 56% with radiotherapy Alone .overall survival was similar in all groups
Resectable advanced lesions not suitable for organPreservation ;-the important part in preservation isthe preservation of the function .once function isIrreparably lost , these is little benefit to preservingThe anatomy .in other cases concurrent chemo-may be toxic due to other diseases or refuse stop smoking /co- morbidities /unreliable who cutting medication /patients who emotionally would preferSurgery / cartilage destroyed or extracapssular extension. 2studies show that stage111 loco regionalControl improved by adding cisplatin concurrent with
Radiation therapy tech- ;-the fields include the primary site (tumor +ve LNs) +subclinical LNSThe upper border includes the nodes in the upper jugular region. both the ipsilateral and contra lateralPosterior are include in the treatment portals if anterior chain +ve.The primary site &area with↑risk(dissected and hasAltered vascular supply)60-66GY 33fr .While area of low risk(not dissected) will receive50-54 fr .
unresectable advanced lesion not suitable for organPreservation ;- in unresectable patients with good general condition with no heamatogenus spread can be approached with curative- intent chemotherapy-enhanced radiation therapy . In veryFit patients inducation chemotherapy succeeded byChemo—enhanced radiation therapy .for patient withAlready distant metastasis role will be palliation
Post-operative radiation therapy .Radiation is indicated for all lesion extentTech – 60-66 GY to operative bed and drainageNodes .Chemo- ;-indicated for microscopically involved mucosal margin /extra capsular extension of nodalDisease .Tech- I-V ;-cisplatin 1 on day 1 ,22 and 43 of radiotherapy treatment .
The volume delineation ;-The primary tumor site,all nodal beds at risk of subclinical disease and operative bed . The upper border include the nodes in jugular region .the highRisk region→ 60-66 GY .low risk→50-54 GY .
Supporting clinical evidenceRTOG 9501 459 patients . Who ,after definitive surgery , had histologic invasion Of tow or more regional LNs/extra capsular extension of nodal disease Or mucosal resection margin. Randomized to radiotherapy alone o(60-66GY) versus identical treatment +concurrent cisplatin on day 1 ,22 &43 . The primary end point of loco regional control favored concurrent chemotherapy at 2 yrs 82% ( with chemotherapy ) versus 72% (no chemotherapy ). The secondary end point of disease free survival also favored concurrent Therapy ( p=0.04) but over all survival not different
EORTC Patients number 334 ,who after definitive surgery had22931 histological Evidence of extra nodal spread , + ve margin , per neural involvement Or vascular tumor embolism (median fallow up 60 months ) Randomized to radiotherapy alone (66 GY in 33 fr) versus identical treatment +concurrent cisplatin in day 1, 22 &43 . The primary end point of disease free survival favored concurrent therapy At 5 yr s4% with chemotherapy verus36% (no chemotherapy) p=o.o4 Second end point of overall survival(p=0.02) and loco regional control (p=0.007) both significantly favored concurrent therapy
schedule frequencyFirst follow up 2weeks after radiation →for acute reactionYrear0-1 Every monthYear 1-2 Every 2 monthsYear2-3 Every 3 monthsYear 3+ Every 6 months
From the previous data of RTOG 9501and EORTC 22931Which concurring the benefit of chemotherapy.Were the ECE (extra capsular extenation) or +ve SM.Involvement of2 more LNs by tumor is not predictBenefit from chemotherapy .
The emis is to controlling thedistressing loco-Regional signs or symptoms of disease for during the patient remaining alive .For who have one or tow non life threatening lesion .with good response to chemotherapy ,the radiationTherapy that approaches the intensity of definitiveTreatment. With more advanced metastatic diseaseThe author tends to favor asplit-course( eg;-30GY in 2weeks the tow weeks rest ,followed by another30 GY in 2weeksto smaller field never over lap the spinal cord.for patient live more we can do quadShot technique
Supporting clinical evidence ;-For M0tumor Multi-institutional phase 111 trial includeing 295 patient with unresectable Nondisseminated ,head and neck cancer. Randomized to stander radiation therapy alone (70YG in 30 fr ) versus Identical radiation +concurrent bolus cisplatin on day 1 ,22 ,34 versus Split-course radiation therapy + bolus cisplatin and continuous –infusion Fluorourcil . The with concurrent cisplatin is associated with improve of The survival,at the cost increase the toxicity .the 3yrs overall survival 37% .
For M0 166 patients with locally advanced ( 74% operable and 26%tumor unoperable)laryngeal and hypophyaryngealcancer . Randomized to to treatment with docetaxel (taxotere) ,cisplatin And 5-fluorourcil inducation then chemoradiotherapy versus Cisplatin and fluorourcil (pf) then chemoradiotherapy . For inoperable 2 yrs overall survival was 55% with TPF AND 41% In the PF . for inoperable tumor ,the 2 yrs progression free survival was 42% In TPF and 30% in the PF .
For MI 30 patients who had advanced head and neck nearly stage 1vTUMOR With performance score of 2-3 . Quad shot =14 GY in 4fr given twice a day at least 6hours apart Over 2 consecutive days ahd repeated up to twice more every 4 weeks . 53% objective reponse rate ( complete reponse,2, partial response ,4.) . Median progression free survival3,1 months . Median overall survival 57 months . 44% patients had measurable improvement in the quality of life
Dose limitation gude line in the ca larynxOrgan at risk Dose limitation (GY)spinal cord 45brachial 60plexusmandible 70posterior <35 (astrip of normal tissue shouldneck be left to facilitate Drainge )