NON SMALL CELLLUNGE CANCER

DR…OMARHASHIM

Most common noncutaneous cancer in the world . The 2nd common cancerIn us . The lunge cancer is the most frequent cause of cancer death.Etiology ;-1. 80—90 % of cases due to smoking .Is related to the number of cigarettes … number of yrs …. Type of cigarette2. Asbestos .3. previous radiotherapy to the chest .4. Inhalation of radon gas , polycyclic aromatic hydrocarbon , nickel ,chromateInorganic arsenical .Types of NSCLC ;-I. AdenocarcinomaII. Bronchioalveolar carcinoma .III. Squamous cell carcinoma .IV. Large cell carcinoma

Pathogenesis Two theories were proposed to explain

lung cancer:1) Multicellular model: considering small cell

carcinoma of neural crest (neuroectodermal) origin and other carcinomas of endodermal origin

2) Unicellular model: considering that all types of carcinomas arise from a single multipotent stem cell capable of variety of phenotypes

Carcinogenesis is a multistep process including activation of proto oncogenes and loss of tumor suppressor genes

In the NSCLC proto-oncogene activation ras +ve ……. C-erb-b 1 , C-erb –b2 + veOncosuppressor gene inactivation P 53 → 50 % …………. RP → O.O% . CLINICAL FEATURE;- Persistent cough …. Recurrent chest pain …. Pleural effusion …. Hoarse ofVoice ….wheeze , strider . … superior vena cava obs - …… horner s syndrome . wt loss … anorexia ……•Paraneoplastic syndromes ;- ( restricted ) 1- hypercalcemia . 2- hypertrophic pul osteoarthropathy . ….. adenocarcinoma3-Gynecomastia ,…..large cell 4- hypercoagulable …… adenocarcinoma 5- carcinoid = VIP dirrhea

Workup ;-H &P ………. Performance status , wt los , smoking status ... Labs CBC…. BUN …. Cr … LFT …. Alkline phosphate . Imaging ;- CT chest & abd ;- size &site of 1ry tumor …. Relationship toLunge fissure , mediastinum , chest wall ….. Mediastinal or other l ns Metastatic disease (lunge ,, liver ,, adrenal ,, bone ) CT brain &bone scan if clinical suspicionPET scan for more sensitivity and specificity for pathological confir - than CTMRI brain for LNs + non squ and all stage 3 & 4 MRI ;-of the thoracic inlet for superior sulcus tumors to assess vertebralBody & brachial plexus invasion .Pathology ;-- thoracentesis for pleural effusion . For central lesions . Perform bronchoscopeCT guided biopsy for peripheral lesion , perform Ct guided biopsy .Mediastinoscopy or bronchoscopic biopsy

Staging ;-T1 ;-tumor 3cm or less in diameter , surrounded by lunge or visceral pleuraDistal to the main bronchus .………………………………………………………………………………T2 ;- tumour > 3cm diameter , involving main bronchus 2cm or more distal To the carina , or invading visceral pleura , or associated with atelectasisWhich extends to the hilum but not involve the whole lunge .……………………………………………………………………………………….T3 ;-tumour invading chest wall , diaphragm . Mediastinal pleura ,or peri –Cardium ,or tumour in main bronchus < 2cm distal to carina or atelectasisOf the whole lunge .………………………………………………………………………………T4 ;- tumour invading , mediastinum , heart , great vessels , trachea , oesophagusVertebra , or carina , or intralober tumour , or malignant pleura effusion .

N0 ;-… no regional node metastases……………………………………………………………N1 ;- Ipsilateral peribronchial or hilar node involvement………………………………………………………N2 ;- Ipsilateral mediastinal or sub carinal nodes .…………………………………………………N3;- contra- lateral mediatinal nodes or supraclavicular nodes .………………………………………………………………………………………………………………………..Staging grouping ;-I. T1 -2 N0 .II. T1-2N1 or T3 N0 .III. a ]T1-2N2 , or T3 N1-2 b ] T 4 any N M0 , or any N3 M0 .IV. Any M1

TREATMENT RECOMMDATION ;-Stage 1 , 2 ;- operable Lobectomy ;- ….. Wedge resection only if physiologically compromised , LNSampling or resection general indicated . For completely resected T1-2N1 Give adjuvant chemo . Aduj- CH for T2N0 if > 4cm .Aduj CH for completely resectable T3N0 .RT for close +ve sm .Outcome ;- LRF …lobectomy 6% ….wedge 18% … 5 yrs os & CSS stage 1 50- 70 %………………………………………………………………………………..Stage 1,2 ;- marginally operable ;-Pre-op chemo → surgery → chemo .Chemo ;-.. Cisplatin com- or carboplatin-paclitaxel .•For close + ve sm → post op RT•Outcome ;- 5 yrs os N1 50 %•……………………………………………………………………………………………… Stage 1,2 ;- inoperable ;- definitive RT to 1ry & LNConventional fractionation is 2gy /fx to 66 Gy

if peripheral tumour or poor PS may hypofractionate with 4Gy /fx to 45 GyTo 1ry tumour only .Outcome ;- std RT 5 yrs T1N0 ; 30 – 50 % .Hypo-fx 2-3 yrs os 40 --- 50 % .SBRT ;- 2-3 Yrs lc 85 -95 % …os 55 % . Dose escalation > 70 Gy & SBRT TECH- 60 Gy/3fx improved LC compared toConventional tech- & dose . If pts can tolerate it , give chemo ( inducationConcurrent and cnsolidation ) if T3N0 chemo should be avoided concurrentlyWith dose escalated RT or SBRT until further data are available .…………………………………………………………………………………………………………Stage 3 a ( operable – marginally operable ) ;-concurrent chemo – RT (45 Gy )Restage → if no progression → surgery → chemo specially if inilially Bulky or multipl N2 nodes .Alternatively , chemo alone →retage →if no progression → surgery → chemoAnd post op RT for close < 5mm or +ve sm , ECE or N2 disease .•If unresectable after restaging → complete definitive concurrent chemo --RT ( 63Gy) . .

Outcome ;- 5 yrs os 20 – 25 % , MS . 16 -17 months inducation chemo –RT pcR rate 15-20% post- op RT possible 5 – 10 % os benefit for N2…………………………………………………………………………………………….Stage 3 ( inoperable ) ;-Concurrent chemo –RT ( 63 Gy ) → aduj chemo . If unacceptable risk of Pneumonitis with upfront RT , consider inducation chemo for down staging→concurent chemo –RT to ( to postchemo volume ) . If no progression .Outcome ;-5 yrs os andMS concurrent chemo- RT 20 -25 % , 16 – 17 months .Sequential chemo –RT 20% , 13 -15 months , RT alone <10 % , 10 -12 months……………………………………………………………………………………………………………Stage 3 b ( no pleural effusion ) ;-Concurrent chemo –RT ( 61-63 ) , IF unacceptable risk of pneumonitis withUpfront RT, consider induction chemo for down- staging → concurrentChemo-RT (to postchemo volume ) if no progression .If T4 N0 may treated with surgery → chemo ± RT ( if residual or ± SM ) orChemo ±RT → surgery → chemo

Typical chemo ;- postsurgery ;-Cisplatin 100mg/mxm d1 & etoposide 100mg/m xm d1-3 every 4 week x4Cycle . Other combinations with vinorelbine , vinblastine , gemcitabine & docetaxelMay be consider .Alternatives ;- if not able to tolerate cisplatin ; carboplatin , paclitaxel every3week for 4 cycles .Concurrent with RT ;Cisplatin 50mg/mxm d1 , 8 , 29 & 36 and etoposide 50mg/mxm d1 -5 &29-33 .Alternative ; cisplatin week 1 & 4 vinblastine weekly , or carboplatin &pacli-Taxel weekly .Sequential chemo – RT Cisplatin 100 mg/ mxm d1 , 29 & vinblastine 5mg/ mxm weekly x 5 weekAlternative carboplatin & paclitaxel every 3week x2 cycles .Consolidation chemo after chemo –RT ;-Carboplatin & paclitaxel every 3 week x 2 cycles .Local treatment as necessary (E.G pleurodesis ) & treat as stage 4 .

Stage 4 ;-Platinum – based chemo ± bevacizumab ± palliative RT . Frist line chemo uses 2agents with response assessment after each cycle , for up to 4-6Cycles or until progression .