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  • 1. NON SMALL CELLLUNGE CANCERDR…OMARHASHIM
  • 2. Most common noncutaneous cancer in the world . The 2nd common cancer
    In us . The lunge cancer is the most frequent cause of cancer death.
    Etiology ;-
    80—90 % of cases due to smoking .
    Is related to the number of cigarettes … number of yrs …. Type of cigarette
    Asbestos .
    previous radiotherapy to the chest .
    Inhalation of radon gas , polycyclic aromatic hydrocarbon , nickel ,chromate
    Inorganic arsenical .
    Types of NSCLC ;-
    Adenocarcinoma
    Bronchioalveolar carcinoma .
    Squamous cell carcinoma .
    Large cell carcinoma
  • 3. Pathogenesis
    Two theories were proposed to explain lung cancer:
    Multicellular model: considering small cell carcinoma of neural crest (neuroectodermal) origin and other carcinomas of endodermal origin
    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
  • 4. In the NSCLC proto-oncogene activation ras +ve ……. C-erb-b 1 , C-erb –b2 + ve
    Oncosuppressor gene inactivation P 53 -> 50 % …………. RP -> O.O% .
    CLINICAL FEATURE;-
    Persistent cough …. Recurrent chest pain …. Pleural effusion …. Hoarse of
    Voice ….wheeze , strider . … superior vena cava obs - …… horner s syndrome .
    wt loss … anorexia ……
    • Paraneoplastic syndromes ;- ( restricted )
    1- hypercalcemia .
    2- hypertrophic pul osteoarthropathy . ….. adenocarcinoma
    3-Gynecomastia ,…..large cell
    4- hypercoagulable …… adenocarcinoma
    5- carcinoid = VIP dirrhea
  • 5. 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 to
    Lunge fissure , mediastinum , chest wall ….. Mediastinal or other l ns
    Metastatic disease (lunge ,, liver ,, adrenal ,, bone )
    CT brain &bone scan if clinical suspicion
    PET scan for more sensitivity and specificity for pathological confir - than CT
    MRI brain for LNs + non squ and all stage 3 & 4
    MRI ;-of the thoracic inlet for superior sulcus tumors to assess vertebral
    Body & brachial plexus invasion .
    Pathology ;--
    thoracentesis for pleural effusion . For central lesions . Perform bronchoscope
    CT guided biopsy for peripheral lesion , perform Ct guided biopsy .
    Mediastinoscopy or bronchoscopic biopsy
  • 6. Staging ;-
    T1 ;-tumor 3cm or less in diameter , surrounded by lunge or visceral pleura
    Distal 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 atelectasis
    Which 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 atelectasis
    Of the whole lunge .
    ………………………………………………………………………………
    T4 ;- tumour invading , mediastinum , heart , great vessels , trachea , oesophagus
    Vertebra , or carina , or intralober tumour , or malignant pleura effusion .
  • 7. 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 ;-
    T1 -2 N0 .
    T1-2N1 or T3 N0 .
    a ]T1-2N2 , or T3 N1-2 b ] T 4 any N M0 , or any N3 M0 .
    Any M1
  • 8. TREATMENT RECOMMDATION ;-
    Stage 1 , 2 ;- operable
    Lobectomy ;- ….. Wedge resection only if physiologically compromised , LN
    Sampling 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
    • 9. Outcome ;- 5 yrs os N1 50 %
    • 10. ………………………………………………………………………………………………
    Stage 1,2 ;- inoperable ;- definitive RT to 1ry & LN
    Conventional fractionation is 2gy /fx to 66 Gy
  • 11. if peripheral tumour or poor PS may hypofractionate with 4Gy /fx to 45 Gy
    To 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 to
    Conventional tech- & dose . If pts can tolerate it , give chemo ( inducation
    Concurrent and cnsolidation ) if T3N0 chemo should be avoided concurrently
    With 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 -> chemo
    And post op RT for close < 5mm or +vesm , ECE or N2 disease .
    • If unresectable after restaging -> complete definitive concurrent chemo
    --RT ( 63Gy) . .
  • 12. 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 osandMS 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 with
    Upfront RT, consider induction chemo for down- staging -> concurrent
    Chemo-RT (to postchemo volume ) if no progression .
    If T4 N0 may treated with surgery -> chemo ± RT ( if residual or ± SM ) or
    Chemo ±RT -> surgery -> chemo
  • 13. Typical chemo;- postsurgery ;-
    Cisplatin 100mg/mxm d1 & etoposide 100mg/m xm d1-3 every 4 week x
    4Cycle .
    Other combinations with vinorelbine , vinblastine , gemcitabine & docetaxel
    May be consider .
    Alternatives ;- if not able to tolerate cisplatin ; carboplatin , paclitaxel every
    3week 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 week
    Alternative 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 .
  • 14. Stage 4 ;-
    Platinum – based chemo ± bevacizumab ± palliative RT . Frist line chemo
    uses 2agents with response assessment after each cycle , for up to 4-6
    Cycles or until progression .