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Management of Carcinoma lung



      Moderator : Dr Seema Gupta
      Presenter : Dr Sandip Barik
                 Dept of Radiotherapy
                 CSMMU
EPIDEMIOLOGY
•   Lung cancer is the most common cancer worldwide contributing about
    12.2% of all new case diagnosed
•   It is the most common cause of cancer in men worldwide(about 16.5%
    )
•   It is the most common cause of cancer related death world wide
    about(18.2% of all death)

•   In India incidence is about 12.1 men /100,000 population

•   Change in trend is seen with incidence increasing in women (0.4% per
    year)and decreasing in men from year 1990

•   Occurs most commonly between 40-70 yrs of age with peak incidence
    at 50s or 60s
RISK FACTORS
• Smoking is the primary risk factor(87% of lung cancer occur in
  smokers

• Average smokers have 10 fold greater risk,while heavy
  smokers(40 cigarettes/day) have 60 fold greater risk

• Women have higher susceptibility to tobacco carcinogen than
  men do

• Introduction of filter cigarettes entices smokers to take larger
  puffs and retain smoke longer

• Second hand smoke or environmental tobacco smoke is
  estimated to cause about 3000 deaths/year
Risk factor cont…
• Industrial agents like asbestos,coaltar fumes,nickle
  ,chromium,arsenic,radioactive materials,radon gas are
  carcinogenic

• Genetic alterations with mutations in p53,RB1,p16(INK4a)

• Dominant oncogenes frequently involved include c-
  MYC,KRAS,EGFR,c-MET and c-KIT

• Precursors lesions like squamousdysplasia,atypical
  adenomatous hyperplasia,diffuse idiopathic pulmonary
  neuroendocrine cell hyperplasia

• Vitamin A,C,E have protective effect
NATURAL HISTORY
• Lung carcinoma arise most often in and about the hilus of lung

• About 3/4th of the lesion originate from 1st,2nd,3rd order bronchi

• Local spread to intrathoracic areas

• The incidence of scalene (supraclavicular)node ranges from 2% to
  35%

• Metastasis to these nodes are from ipsilateral upper lobes


• Metastasis also occur in cervical,axillary and inguinal lymphnodes
Natural hist cont…
• Extrathoracic spread

• Undifferentiated small cell cancer (oat cell variant) has a higher
  incidence of distant metastasis than nonsmall cell types

• Among Non small cell group Adenocarcinoma have a greater
  propensity for distant metastases
LYMPHATIC DRAINAGE
• During the past three decades two different lymphnode
  station have been used
• 1st was the Japanese Lung Cancer Society Classification
• 2nd was the Mountain Dressler Modification of the
  American Thoracic Society(MDATS)
• Recently the International Association For The Study Of
  Lung Cancer(IASLC) proposed a lymphnode map
• It provides more detailed nomenclature for the anatomic
  boundaries of lymphnode station
• The IASLC is now the recommended means of
  describing regional lymphnode in lung cancer
LYMPHNODE STATION
             Supraclavicular    1.Low
                                cervical,supraclavi
                                cular,sternal notch
             Superior           (2R,2L)Upper
             Mediastinal        Paratracheal
                                (3a,3p)Pre
                                vascular,Retrotrach
                                eal
                                (4R,4L)Lower
                                paratracheal
             Aortic             (5,6)Subaortic,Par
                                aaortic
             Inferior Mediastinal 7 Subcarinal
                                  (8,9)Paraoesophag
                                  eal,pulmonary
                                  ligament
             N1 nodes           (10,11,12,13,14)
                                Hilar,interlobar,loba
                                r,segmental,subse
                                gmental
• The lymph from right lung
  involves lower paratracheal
  nodes(iv) followed by
  subcarinal (vii)


• The lymph from left upper
  lobe involve subaortic
  nodes(v)


• The left lower lobe drains to
  subcarinal lymphnodes(vii)
WORLD HEALTH ORGANISATION
        CLASSIFICATION OF MALIGNANT LUNG
•    MALIGNANT        CANCER
1.   SQUAMOUS CELL CARCINOMA        5   ADENOSQUAMOUS
a      Spindle cell variant         6   CARCINOID
2.   SMALL CELL CARCINOMA           7   BRONCHIAL GLAND
a     Oat cell                          CARCINOMA
b     Intermediate cell
C      Combined
3.   ADENOCARCINOMA
A     Acinar
B      Papillary
C      Bronchioalveolar
D      Solid carcinoma with mucin
4.   LARGE CELL CARCINOMA
A     Giant cell
B      Clear cell
PATHOLOGICAL
                        CLASSIFICATION
•   Squamous cell carcinoma is the most
    commonly found in men

•   It is closely related with smoking
    history

•   Adenocarcinoma has been common
    type of lung cancer in women and
    nonsmokers since 1950*

•   From 1990’s adenocarcinoma is the
    most common diagnosis in men*i

•   Currently Adenocarcinoma has
    surpassed Squamous cell type
Classification (cont…)

   Non Small Cell              Small Cell Lung
    Lung Cancer                 Cancer (SCLC)
    (NSCLC)
                            • Oat Cell
• Adenocarcinoma
                            • Intermediate
• Squamous Cell Carcinoma
                            • Combined
• Large Cell Carcinoma
CLINICAL PRESENTATION
•    Although no set of signs and symptoms are
     pathognomic for carcinoma lung they can be
     broadly divided into three categories

1.   Due to local tumour growth and intrathoracic
     spread

2.   Due to distant metastasis

3.   Nonspecific systemic symptoms or paraneoplastic
     syndromes
Due to local tumor and intrathoracic spread
•   Squamous and small cell cancers usually present as central mass

•   They produce cough,wheeze,hemoptysis

•   Symptoms and signs of airway obstruction &postobstructive
    pneumonitis(dyspnoea,fever,productive cough)

•   Adenocarcinoma and large cell tumour present as peripheral
    mass with pleural involvement

•   More likely to be asymtomatic but may cause pleuritic chest
    pain,cough

•   Squamous and large cell cavitate in 10-20% of cases
Intrathoracic spread
• Usually causes nerve entrapment

• Most commonly causes left
  recurrent laryngeal nerve palsy
  leads to hoarseness, dysphagia
  recurrent aspirations
• Phrenic nerve entrapment leads
  to hiccups
• Apical tumours causes Pancoast
  syndrome, lower
  brachialplexopathy(C8,T1),
  Horners syndrome, shoulder pain

• Most superior sulcus tumour are
  squamous cell type
Intrathoracic spread

•   Compression of esophagus
        dysphagia
         recurrent aspirations
        tracheoesophageal fistula
        bronchoesophageal fistula

•   Principal vascular syndrome
    caused is Superior vena cava
    syndrome

•   Usually caused by tumour on
    right upper lobe or right main
    bronchus

•   Most commonly caused by
    small cell type followed by
    squamous cell
Intrathoracic spread
• 50% of patients with disseminated lung cancer develops pleural
  effusion
• Lung cancer is the single most cause of pericardial metastases
SYMPTOMS DUE TO
              METASTASIS
• Most common sites of haematogenous spread that are clinically
  apparent are brain,bones,liver,adrenals

• Extrathoracic metastatic disease found at autopsy in
       50% with squamous cell carcinoma
       80% with adenocarcinoma and large cell
       95%with small cell cancer

• Symptoms are according to the organ involved

• Adrenal metastases are common but rarely cause adrenal
  insufficiency
NONSPECIFIC AND PARANEOPLASTIC
                SYNDROMES
• Paraneoplastic syndrome refer to the disorders that accompany
  tumours but not directly related to mass effect or invasion
• Endocrine syndromes
      hypercalcaemia,hypophosphataemia due to parathyroid
      hormones by squamous cell.
        Hyponatraemia with SIADH by small cell
        hypokalemia due to ACTH by small cell
•   Clubbing in non small cell type
•   Hypertrophic pulmonary osteoarthropathy in adeno carcinoma
•   Neurologic myopathic syndromes like Eaton lambert
•   Trousseau’s syndrome
•   Dermatomyositis and Acanthosis nigricans
•    Detail History
•    Physical Examination
•    Chest xray
1.   It is the single most important and initial investigation
2.   It can present in different ways depending on the region of lung
     involved and histology
               Hilus             Hilar prominence,hilar mass,perihilar
                                 mass
               Pulmonary         Mass,apical mass,multiple
               parenchyma        masses,bronchial
                                 obstruction,collapse,consolidation

               Intrathoracic     Mediastinal widening or mass,chest
               extrapulmonary    wall erosion,pleural effusion,elevation
               structure         of diaphragm
Chest x-ray cont..
Squamous cell    Collapse,consolid
carcinoma        ation,cavitation,hil
                 ar abnormality


Adenocarcinoma   Peripheral
                 mass,hilar
                 abnormality,obstr
                 uctive lesion,no
                 cavitation
Large cell       Peripheral
carcinoma        mass,cavitation
                 and hilar
                 abnormalities rare
Small cell       Hilar prominence
tumours
Confirmatory workup

•   Sputum cytology:it has a posive predictivity value of 100%,but sensitivity
    of 10-15%

•   Bronchoscopic biopsy

•   Transbronchial fine needle aspiration
       Used for central lesions
       Evaluation of mediastinal lymphadenopathy

•   Bronchoalveolar lavage
      peripheral regions not visible endoscopically

•   CT guided transthoracic percutaneous fnac/biopsy
Staging workup
1.   CECT THORAX
        Sensitivity 75%,specificity 66%
        CT scan should extend inferiorly to include upper abdomen and adrenal
     glands
2.   FDG PET SCAN
        Sensitivity 91%,specificity 86%
        Can detect lesions >5 to 8 mm on basis of FDG uptake
        Combinations of CT scan and PET scan has greater sensitivity and
     specificity   than CTscan along

3.   FIBREOPTIC BRONCHOSCOPY
        Most important procedure for determining the endobronchial extent of the
        disease,measuring tumour proximity to carina
4.   MEDIASTINOSCOPY
        Best method to evaluate the upper,middle peritracheal and subcarinal
        lymphnodes
5.   BONE SCAN/CT-MRI OF BRAIN
6.   ULTRASONOGRAPHY WHOLE ABDOMEN
Blood
• Haemogram
• Kidney func test
• Liver func test
• Serum electrolytes
• Hormones like parathyroid,ACTH
Urine
• Routine & microscopic
AJCC STAGING(2010)
Tx    Primary cannot be accessed or positive cytology

To    No evidence of primary tumour


Tis   Carcinoma in situ

T1    Tumour <3cm greatest dimention surrounded by lung or visceral pleura
      without bronchoscopic evidence of invasion more proximal than lobar
T1a   bronchus(i.e not in main bronchus)
      Tumout 2 cm or less in greatest dimention
T1b
      Tumour >2cm but 3cm or less in greatest dimention


T2    Tumour >3cm but 7cm or less or involves main bronchus,>2cm from the
      carina,invades visceral pleura associated with partial atelactasis
T2a   Tumour more than 3cm but 5cm or less
T2b   Tumour more than 5 cm but 7 cm or less


T3    Tumour more than 7 cm or one directly invading the parietal pleura,chest
      wall,diaphragm,phrenic nerve,mediastinal pleura,parietal pericardium or
      tumour in the main bronchus<2cm from the carina but without involvement
      of carina,associated total atelectasis

T4    Tumour of any size invading the mediastinum,heart,great
      vessels,trachea,recurrent laryngeal nerve,esophagus,vertebral
      body,carina,separate tumour nodule in tha same lobe,malignant effusion
Regional
lymphnodes
Nx           Regional node cannot be accessed


No           No regional node metastasis


N1           Metastasis in ipsilateral peribronchial and/or ipsilateral hilar
             node and intrapulmonary nodes including involvement by
             direct extention
N2           Metastasis in ipsilateral mediastinal and/or subcarinal
             lymphnodes
N3           Metastasis in contralateral mediastinal,contralateral
             hilar.ipsilateral or contralateral scalene or supraclavicular
             node
Distant
Metastasis
Mo           No distant metastasis

M1           Distant metastasis

M1a          Separate tumour nodule in a contralateral lobe tumour with
             pleural nodule or malignant pleural or pericardial effusion
M1b          Distant metastasis in extrathoracic organs
PROGNOSTIC FACTORS
•    Epidermoid carcinoma has the best prognosis followed by
    adenocarcinoma and undifferentiated large cell cancer

•   Undifferentiated small cell cancer has the poorest prognosis

•   In Lung cancer the most important prognostic factor is tumor
    stage

•   In SCLC pure cell carcinomas are more sensitive to
    chemotherapy and radiotherapy than variant cell.
Negative prognostic factors are
1.   Mutations in Kras oncogene
2.   Deletion of p53,NCAM molecule
3.   Expression,elevated neuron specific
     enolase level
4.   Over expression of erb1,erb2
5.   Increased proliferative
6.   Markers(ki67,cyclinD1,E,B1,p16 loss
7.   Angiogenesis markers like VEGF
8.   Decreased apoptotic markers like
     caspase 3
Management of NSCLC

Stage I-II :       Early stage(T1-2, N1)



Stage IIIA : Locally advanced (surgery feasible)(T3,N2)



Stage IIIB : Locally advanced (surgery not
feasible)(T4,N3)



 Stage IV      :        Metastatic disease
For Non
 Small Cell
  Cancer        • Surgery
 usually a
multimodality   • Chemotherapy
approach is     • Radiotherapy
    used
Surgery
• Indications

1.   Stage I , II

2. Stage IIIA(T1-3 N2,T3N1)

3. Medically fit

4. Good performance scale
Surgery(cont…)

• Surgery is the standard treatment of choice for patients with
  stage I,II and IIIA tumours.

• Lobectomy with nodal dissection is the method of chioce

• Pneumonectomy is done only when
      Involves proximal bronchus or proximal pulmonary artery
      Crosses major fissure

• Wedge resection is only restricted to persons who are not able
  to tolerate lobectomy
Lymphnode dissection

The current minimum standard
  is a systemic sampling of
  each lymph node station of
  tumor

Rt sided tumors – 2,3,4,7,8,
   9,tracheobronchial angle
   and interlobar area (10,11)

Lt sided tumors – sub aortic,
    ant med nodes (5,6), 7,8,9
Results

• 5 yrs survival for patients with Stage I is 65%,Stage II is 60%
  ,Stage IIIA( N1 disease is 34%,N2 is 24%)

• Various studies also concluded that lymphnode dissection is
  necessary for accurate staging.

• Lesser resections like wedge resection result in higher
  recurrence rate and reduced survival.

• Survival is longer in clinical (pre op)N0 or N1 disease but
  pathological(post resection N2) than clinical N2 disease
RADIOTHERAPY

Radiation is used in following forms in NSCLC

A.   AS ADJUVANT                 * Post Operative
                                 * Pre Operative


B.   PRIMARY RADIATION            * Radical
                                 * Palliative
C.   CHEMO-RADIATION

NSCLC is a radio responsive tumor but not radiosensitive
Role of pre op irradiation

• Indications
1. In stage I,II,III tumours
• Dose :20 Gy in 5#

•   Results

•   Multi institutional trail compared preop RT vs surg alone

•   No added benefits was found in stage I,II Tumours

•   But a significant 3 yr survival rate (49.4% vs 28.1%) was
    observed in stage III
Role of Post op RT

• Indications

1.   Incomplete resection
2.   Close or positive margins
3.   Positive mediastinal metastases
4.   Resected N2 disease
5.   Chest wall involvement
6.   Superior sulcus tumour

• Contraindications
1. Currently contraindicated in patients with stage I completely
   resected
Post op RT(cont…)

Dose for potential microscopic   Dose for margins positive 60 to
disease 50 GY                    66 Gy

RESULTS
TRIALS                           •PORT Meta Analysis
                                 •SEER Database
                                 •British Medical Research
CONCLUSIONS                      •Role of PORT in positive N1
                                 disease is controversial
                                 •More data supporting role in N2
                                 •The studies used conventional
                                 technique
                                 •Modern tech like IMRT,3D CRT
                                 hopefully will increase the result in
                                 favour of PORT
Definitive radiotherapy in NSCLC (early stage)

INDICATIONS :
•     1. Medically inoperable T1-T3 lesions.

•      2. Patient refuses surgery.

•      3. Critically located lesion.

•      4. Non-resectable Stage-II & Stage-IIIA
•
•      5. Patient with incomplete resection.

•      6. Localized recurrent lung cancer.
RADIOTHERAPY TECHNIQUES
 Conventional External beam radiotherapy

• VOLUME
  2 cm around the tumour margin

• ENERGY
  6-10 Mev linac

• PORTALS
  2 to 3 fields depending on tumour and lymphnodes

• DOSE
  60-66 GY @1.8-2 GY/#
Results of Radiotherapy in early stage

• Local control is poor and results are not very encouraging for
  NSCLC

• 5yr local control and overall survival rates ranges from 30 to
  50% and 10-30%

• Results of conventional RT is certainly inferior when compared
  with other modality
STEREOTACTIC BODY RADIATION THERAPY

• SBRT is a combination of multiple beam angles to achieve
  sharp dose gradients,high precision localisation and a high
  dose per fraction in extracranial locations.

• Delivers a high biologic effective dose BED to target

• Minimise normal tissue toxicity

• Reduced treatment volume

• Reducing treatment time
SBRT
• Results of SBRT

 Image guided SBRT with delivery of BED>100 GY is feasible
  and produces better results than <100 gy

 3 to 5 yr survival rate and local control is much more better
  than those for conventional RT

 For stage I A disease results are comparable with surgery

 Emerging as the standard treatment for inoperable stage I
  NSCLC.
Definitive RT In Advanced NSCLC(stage III)

• Larger unresectable tumours T4N0-1 or T1-4 N2-3.

• Dose given is 60 GY @2GY/#

• A higher dose upto 80 to 100 gy is required to improve local
  control and potential survival but toxicity is main limiting factor
  here.

• However advanced such as 3D crt and imrt have provided a
  way for dose escalation with out toxicity.
non small cell lung cancer
              newer radiation techniques

1.   3-Dimentional Conformal Therapy.
2.   Intensity Modulated Radiation Therapy.
3.   IGRT and Gated Radiotherapy.
4.   Interstitial Brachytherapy.
5.   Endobronchial Brachytherapy.
6.   Intra Operative Radiotherapy.
3-D CRT & IMRT IN LUNG CANCER

Goal:
        To increase dose delivery to tumour
        To minimize dose to normal tissues.

Advantages

1.      Better conformity of radiation dose to the tumour.
2.      Sparing of all the vital structures around tumour.
3.      Escalation of dose is possible.
4.      Better control of disease.
5.      Reduced morbidity.
3-D CRT & IMRT IN LUNG CANCER
     TREATMENT PLANNING
Radiotherapy planning
• GTV (Gross Tumor volume)
• CTV (Clinical Target volume)
• PTV (Planning Target volume)

• GTV
  Visible tumor by any imaging modality
  including the lesion and lymphnode > 1
  cm.
RT-Planning – Defining the CTV

CTV is the volume that contains gross and microscopic
disease

A Radiographic histopathologic study demonstrated that
CTV varies with histologic type



    Microscopic extension     Adeno       Squamos
    mean value               2.69mm       1.48mm
    5mm margin covers:         80%          91%
    margin to cover 95%       8mm           6mm
PTV
• One of the important reason of uncertainty in ca lung
  is motion of the tumor during respirations

• PTV is defined as CTV with a margin to account for
  daily set up error and target motion
NON SMALL CELL LUNG CANCER
         RADICAL RADIATION
Image Guided RadiationTherapy-IGRT:

It is defined as the use of modern imaging modalities specially
those incorporating functional and biological information.
       1. To augment target delineation

     2. Use of imaging to adjust to target motion and
        positional uncertainty- respiratory gated therapy

     3. Potential to adopt treatment to tumor
        response.
IMAGE GUIDED RADIATION THERAPY

                EQUIPMENT REQUIRED




 CT-SCAN        MRI                 PET-CT

Linac with on         Tomotherapy            Cyber knife
Board imaging
Chemotherapy
        (NCCN Guidelines 2010)
• Indicated in all stages above stage Ib, significant
  improvement in survival.

• First line
- Premetrexate + cisplatin is superior to Gemcitabine +
   cisplatin in non sq cell tumors.
- Paclitaxal + carboplatin for sq cell tumors.
- Bevacizumab and Erlotinib combined with
  chemotherapy.
- No use of using a third drug in the regime.
- Older patients single agent chemotherapy is adviced
•   Second line (in combination with platinum)
-   Docetaxal
-   Premetrexate
-   Irinotecan
-   Erlotonib

• Third line
- Erlotinib
- Vinorelabine
SMALL CELL LUNG CANCER
Staging of SCLC
     Veterans Administration Lung Study Group (VALG) staging
       system

• Limited-Stage Disease (LD SCLC )
  - Confined to the hemithorax of origin, the mediastinum, or the
  supraclavicular nodes, which can be encompassed within a
  tolerable radiation therapy port.



• Extensive-Stage Disease (ED SCLC)
   - Any disease not meeting limited stage criteria
  - Distant metastasis.

•
Staging of SCLC
• The International Association for the Study of Lung
  Cancer (IASLC) revised the VALG classification in
  accordance with the TNM system.

      - LD definition is consistent with TNM stages I to
       IIIB.

      - ED is limited to patients with distant metastases.
Management of SCLC
• SURGERY

1. Stage I(T1-2,N0)

2. Lobectomy with mediastinal nodal dissection is the surgery of
   choice

3.   Early stage SCLC is diagnosed in fewer than 5% of SCLC
     patients,limits the scope of surgery

4. The trial by Medical Research Council led to abandonment
   of surgery as a primary modality of treatment
Combined Chemotherapy and Radiation
                 therapy
• Indications

1. To decrease the local recurrence

2. To improve survival

3. Positive lymphnode involvement after surgery
Role of Radiotherapy
• Meta-analysis by Warde and Payne
  - 11 prospective trials of chemotherapy with or without RT were
   analysed
 - Results : Absolute increase of OS by 5.4 % at 2 years
              Local control of 25 % with limited stage disease

•      Pignon et al
    - 16 randomized studies with 2,140 patients
    - improvement in abolute survival of 5.4 % at 3 years




    Definite role for RT in local control of disease
    which leads to increase in overall survival
Role of chemo radiotherapy
      McCracken et al (154 patients)
                                       Results
Cisplatin , Etoposide
                                  Time         Survival
& vincristine 2 cycles
                                  2 yr           42 %
with RT 1.8 Gy per
                                  4 yr           30 %
day upto 45 Gy
                                   5 yr          26 %


         Concurrent chemo radiotherapy
         provides good survival advantage
         with tolerable toxicity to the patient
Concurrent Chemoradiation

•    Advantages
1.    Overall shorter treatment time
2.    High dose intensity
3.    Sensitisation of tumours

•     Disadvantages
1.    Enhanced normal tissue toxicity
2.    Treatment breaks
3.    Inability to access response to either mode
Sequential vs Concurrent
            chemoradiotherapy
Japanese Clinical Oncology Group

Arm 1
Paclitaxel 80 mg/m2 on d1 and etoposide
100 mg/m2 d1-3 (2 cycles)
                                            Results showed significant
                                            improvement of survival in
           RT 45 GY                         CRT arm


                                            Conclusion:CRT is better
Arm 2                                       than sequential chemo and
Paclitaxel 80 mg/m2 on d1 and etoposide     radiotherapy
100 mg/m2 d1-3

               +
RT was started along with chemo from day1
Timing of Chemo Radiotherapy
 • NCI Canada trial                     40 Gy in 15 fractions
                                        over 3 weeks to the
                                        primary site concurrent
                                        with the first cycle of EP
All 308 eligible patients received      (week 3)
cyclophosphamide, doxorubicin, and
vincristine (CAV) alternating with
etoposide and cisplatin (EP) every 3
weeks for three cycles of each          late TI patients received
chemotherapy regimen.                   the same radiation
                                        concurrent with the last
                                        cycle of EP (week 15)



                 Overall survival better in Early RT arm
Altered fractionation

            Turrisi et al
                                 Once-daily therapy received
                                 1.8 Gy daily in 25 treatments
417 patients with limited        over a period of five weeks.
small-cell lung cancer.                                             Patients with a
All the patients received four                                      complete response
21-day cycles of                                                    Received prophylactic
cisplatin 60 mg/m2 and                                              cranial irradiation 25
Etoposide 120 mg/m2                                                 Gy 1n 10 #
RT started with CT in first
week                             Accelerated twice-daily thoracic
                                 radiotherapy involved the
                                 administration of 1.5 Gy in 30 #
                                 over a period of three weeks

                            Conclusion : 10% absolute increase in
                            overall survival @ 5yrs with15% increase
                            in high grade esophagitis in Acc RT arm
Prophylactic cranial irradiation

Metaanalysis conducted in 1999 studied 7 prospectively randomised trail




They found a disease free and overall survival advantage in those patients who under went
prophylactic cranial irradiation




Dose is still a matter of debate however there is a trend in reduction of brain relapses at 36 GY
@ 2 GY /#




Prophylactic cranial irradiation should be consideredfor complete clinical responders
CONCLUSION
• NSCLC
1.STAGE I&II
 Surgery if feasible followed by adjuvant chemotherapy when
    indicated
 SBRT if not medically fit
2.STAGE IIIA
 Surgery with adj chemotherapy + PORT
 EBRT with chemotherapy if not fit
3.STAGE IIIB
 EBRT with chemotherapy
4.STAGE IV
 Chemotherapy with EBRT for palliation
CONCLUSION

   SCLC;Limited disease
   CONCURRENT CHEMORADIATION IS CONSIDERED
• Dose of Radiotherapy should be delivered at 45 GY with1.5
  GY/#,twice daily with concurrent Cisplatin and Etoposide.

• Prophylactic cranial irradiation should be considered for
  complete clinical responders.

•   Patients should be encouraged to participate in newer protocol
   Extensive disease
•   Chemotherapy
•   Prophylactic cranial irradiation for responders
•   Palliation
THANKYOU

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Carcinoma lung

  • 1. Management of Carcinoma lung Moderator : Dr Seema Gupta Presenter : Dr Sandip Barik Dept of Radiotherapy CSMMU
  • 2. EPIDEMIOLOGY • Lung cancer is the most common cancer worldwide contributing about 12.2% of all new case diagnosed • It is the most common cause of cancer in men worldwide(about 16.5% ) • It is the most common cause of cancer related death world wide about(18.2% of all death) • In India incidence is about 12.1 men /100,000 population • Change in trend is seen with incidence increasing in women (0.4% per year)and decreasing in men from year 1990 • Occurs most commonly between 40-70 yrs of age with peak incidence at 50s or 60s
  • 3. RISK FACTORS • Smoking is the primary risk factor(87% of lung cancer occur in smokers • Average smokers have 10 fold greater risk,while heavy smokers(40 cigarettes/day) have 60 fold greater risk • Women have higher susceptibility to tobacco carcinogen than men do • Introduction of filter cigarettes entices smokers to take larger puffs and retain smoke longer • Second hand smoke or environmental tobacco smoke is estimated to cause about 3000 deaths/year
  • 4. Risk factor cont… • Industrial agents like asbestos,coaltar fumes,nickle ,chromium,arsenic,radioactive materials,radon gas are carcinogenic • Genetic alterations with mutations in p53,RB1,p16(INK4a) • Dominant oncogenes frequently involved include c- MYC,KRAS,EGFR,c-MET and c-KIT • Precursors lesions like squamousdysplasia,atypical adenomatous hyperplasia,diffuse idiopathic pulmonary neuroendocrine cell hyperplasia • Vitamin A,C,E have protective effect
  • 5. NATURAL HISTORY • Lung carcinoma arise most often in and about the hilus of lung • About 3/4th of the lesion originate from 1st,2nd,3rd order bronchi • Local spread to intrathoracic areas • The incidence of scalene (supraclavicular)node ranges from 2% to 35% • Metastasis to these nodes are from ipsilateral upper lobes • Metastasis also occur in cervical,axillary and inguinal lymphnodes
  • 6. Natural hist cont… • Extrathoracic spread • Undifferentiated small cell cancer (oat cell variant) has a higher incidence of distant metastasis than nonsmall cell types • Among Non small cell group Adenocarcinoma have a greater propensity for distant metastases
  • 7. LYMPHATIC DRAINAGE • During the past three decades two different lymphnode station have been used • 1st was the Japanese Lung Cancer Society Classification • 2nd was the Mountain Dressler Modification of the American Thoracic Society(MDATS) • Recently the International Association For The Study Of Lung Cancer(IASLC) proposed a lymphnode map • It provides more detailed nomenclature for the anatomic boundaries of lymphnode station • The IASLC is now the recommended means of describing regional lymphnode in lung cancer
  • 8. LYMPHNODE STATION Supraclavicular 1.Low cervical,supraclavi cular,sternal notch Superior (2R,2L)Upper Mediastinal Paratracheal (3a,3p)Pre vascular,Retrotrach eal (4R,4L)Lower paratracheal Aortic (5,6)Subaortic,Par aaortic Inferior Mediastinal 7 Subcarinal (8,9)Paraoesophag eal,pulmonary ligament N1 nodes (10,11,12,13,14) Hilar,interlobar,loba r,segmental,subse gmental
  • 9. • The lymph from right lung involves lower paratracheal nodes(iv) followed by subcarinal (vii) • The lymph from left upper lobe involve subaortic nodes(v) • The left lower lobe drains to subcarinal lymphnodes(vii)
  • 10. WORLD HEALTH ORGANISATION CLASSIFICATION OF MALIGNANT LUNG • MALIGNANT CANCER 1. SQUAMOUS CELL CARCINOMA 5 ADENOSQUAMOUS a Spindle cell variant 6 CARCINOID 2. SMALL CELL CARCINOMA 7 BRONCHIAL GLAND a Oat cell CARCINOMA b Intermediate cell C Combined 3. ADENOCARCINOMA A Acinar B Papillary C Bronchioalveolar D Solid carcinoma with mucin 4. LARGE CELL CARCINOMA A Giant cell B Clear cell
  • 11. PATHOLOGICAL CLASSIFICATION • Squamous cell carcinoma is the most commonly found in men • It is closely related with smoking history • Adenocarcinoma has been common type of lung cancer in women and nonsmokers since 1950* • From 1990’s adenocarcinoma is the most common diagnosis in men*i • Currently Adenocarcinoma has surpassed Squamous cell type
  • 12. Classification (cont…) Non Small Cell Small Cell Lung Lung Cancer Cancer (SCLC) (NSCLC) • Oat Cell • Adenocarcinoma • Intermediate • Squamous Cell Carcinoma • Combined • Large Cell Carcinoma
  • 13. CLINICAL PRESENTATION • Although no set of signs and symptoms are pathognomic for carcinoma lung they can be broadly divided into three categories 1. Due to local tumour growth and intrathoracic spread 2. Due to distant metastasis 3. Nonspecific systemic symptoms or paraneoplastic syndromes
  • 14. Due to local tumor and intrathoracic spread • Squamous and small cell cancers usually present as central mass • They produce cough,wheeze,hemoptysis • Symptoms and signs of airway obstruction &postobstructive pneumonitis(dyspnoea,fever,productive cough) • Adenocarcinoma and large cell tumour present as peripheral mass with pleural involvement • More likely to be asymtomatic but may cause pleuritic chest pain,cough • Squamous and large cell cavitate in 10-20% of cases
  • 15. Intrathoracic spread • Usually causes nerve entrapment • Most commonly causes left recurrent laryngeal nerve palsy leads to hoarseness, dysphagia recurrent aspirations • Phrenic nerve entrapment leads to hiccups • Apical tumours causes Pancoast syndrome, lower brachialplexopathy(C8,T1), Horners syndrome, shoulder pain • Most superior sulcus tumour are squamous cell type
  • 16. Intrathoracic spread • Compression of esophagus dysphagia recurrent aspirations tracheoesophageal fistula bronchoesophageal fistula • Principal vascular syndrome caused is Superior vena cava syndrome • Usually caused by tumour on right upper lobe or right main bronchus • Most commonly caused by small cell type followed by squamous cell
  • 17. Intrathoracic spread • 50% of patients with disseminated lung cancer develops pleural effusion • Lung cancer is the single most cause of pericardial metastases
  • 18. SYMPTOMS DUE TO METASTASIS • Most common sites of haematogenous spread that are clinically apparent are brain,bones,liver,adrenals • Extrathoracic metastatic disease found at autopsy in 50% with squamous cell carcinoma 80% with adenocarcinoma and large cell 95%with small cell cancer • Symptoms are according to the organ involved • Adrenal metastases are common but rarely cause adrenal insufficiency
  • 19. NONSPECIFIC AND PARANEOPLASTIC SYNDROMES • Paraneoplastic syndrome refer to the disorders that accompany tumours but not directly related to mass effect or invasion • Endocrine syndromes hypercalcaemia,hypophosphataemia due to parathyroid hormones by squamous cell. Hyponatraemia with SIADH by small cell hypokalemia due to ACTH by small cell • Clubbing in non small cell type • Hypertrophic pulmonary osteoarthropathy in adeno carcinoma • Neurologic myopathic syndromes like Eaton lambert • Trousseau’s syndrome • Dermatomyositis and Acanthosis nigricans
  • 20. Detail History • Physical Examination • Chest xray 1. It is the single most important and initial investigation 2. It can present in different ways depending on the region of lung involved and histology Hilus Hilar prominence,hilar mass,perihilar mass Pulmonary Mass,apical mass,multiple parenchyma masses,bronchial obstruction,collapse,consolidation Intrathoracic Mediastinal widening or mass,chest extrapulmonary wall erosion,pleural effusion,elevation structure of diaphragm
  • 21. Chest x-ray cont.. Squamous cell Collapse,consolid carcinoma ation,cavitation,hil ar abnormality Adenocarcinoma Peripheral mass,hilar abnormality,obstr uctive lesion,no cavitation Large cell Peripheral carcinoma mass,cavitation and hilar abnormalities rare Small cell Hilar prominence tumours
  • 22. Confirmatory workup • Sputum cytology:it has a posive predictivity value of 100%,but sensitivity of 10-15% • Bronchoscopic biopsy • Transbronchial fine needle aspiration Used for central lesions Evaluation of mediastinal lymphadenopathy • Bronchoalveolar lavage peripheral regions not visible endoscopically • CT guided transthoracic percutaneous fnac/biopsy
  • 23. Staging workup 1. CECT THORAX Sensitivity 75%,specificity 66% CT scan should extend inferiorly to include upper abdomen and adrenal glands 2. FDG PET SCAN Sensitivity 91%,specificity 86% Can detect lesions >5 to 8 mm on basis of FDG uptake Combinations of CT scan and PET scan has greater sensitivity and specificity than CTscan along 3. FIBREOPTIC BRONCHOSCOPY Most important procedure for determining the endobronchial extent of the disease,measuring tumour proximity to carina 4. MEDIASTINOSCOPY Best method to evaluate the upper,middle peritracheal and subcarinal lymphnodes 5. BONE SCAN/CT-MRI OF BRAIN 6. ULTRASONOGRAPHY WHOLE ABDOMEN
  • 24.
  • 25. Blood • Haemogram • Kidney func test • Liver func test • Serum electrolytes • Hormones like parathyroid,ACTH Urine • Routine & microscopic
  • 26. AJCC STAGING(2010) Tx Primary cannot be accessed or positive cytology To No evidence of primary tumour Tis Carcinoma in situ T1 Tumour <3cm greatest dimention surrounded by lung or visceral pleura without bronchoscopic evidence of invasion more proximal than lobar T1a bronchus(i.e not in main bronchus) Tumout 2 cm or less in greatest dimention T1b Tumour >2cm but 3cm or less in greatest dimention T2 Tumour >3cm but 7cm or less or involves main bronchus,>2cm from the carina,invades visceral pleura associated with partial atelactasis T2a Tumour more than 3cm but 5cm or less T2b Tumour more than 5 cm but 7 cm or less T3 Tumour more than 7 cm or one directly invading the parietal pleura,chest wall,diaphragm,phrenic nerve,mediastinal pleura,parietal pericardium or tumour in the main bronchus<2cm from the carina but without involvement of carina,associated total atelectasis T4 Tumour of any size invading the mediastinum,heart,great vessels,trachea,recurrent laryngeal nerve,esophagus,vertebral body,carina,separate tumour nodule in tha same lobe,malignant effusion
  • 27. Regional lymphnodes Nx Regional node cannot be accessed No No regional node metastasis N1 Metastasis in ipsilateral peribronchial and/or ipsilateral hilar node and intrapulmonary nodes including involvement by direct extention N2 Metastasis in ipsilateral mediastinal and/or subcarinal lymphnodes N3 Metastasis in contralateral mediastinal,contralateral hilar.ipsilateral or contralateral scalene or supraclavicular node Distant Metastasis Mo No distant metastasis M1 Distant metastasis M1a Separate tumour nodule in a contralateral lobe tumour with pleural nodule or malignant pleural or pericardial effusion M1b Distant metastasis in extrathoracic organs
  • 28.
  • 29. PROGNOSTIC FACTORS • Epidermoid carcinoma has the best prognosis followed by adenocarcinoma and undifferentiated large cell cancer • Undifferentiated small cell cancer has the poorest prognosis • In Lung cancer the most important prognostic factor is tumor stage • In SCLC pure cell carcinomas are more sensitive to chemotherapy and radiotherapy than variant cell.
  • 30. Negative prognostic factors are 1. Mutations in Kras oncogene 2. Deletion of p53,NCAM molecule 3. Expression,elevated neuron specific enolase level 4. Over expression of erb1,erb2 5. Increased proliferative 6. Markers(ki67,cyclinD1,E,B1,p16 loss 7. Angiogenesis markers like VEGF 8. Decreased apoptotic markers like caspase 3
  • 31. Management of NSCLC Stage I-II : Early stage(T1-2, N1) Stage IIIA : Locally advanced (surgery feasible)(T3,N2) Stage IIIB : Locally advanced (surgery not feasible)(T4,N3)  Stage IV : Metastatic disease
  • 32. For Non Small Cell Cancer • Surgery usually a multimodality • Chemotherapy approach is • Radiotherapy used
  • 33. Surgery • Indications 1. Stage I , II 2. Stage IIIA(T1-3 N2,T3N1) 3. Medically fit 4. Good performance scale
  • 34. Surgery(cont…) • Surgery is the standard treatment of choice for patients with stage I,II and IIIA tumours. • Lobectomy with nodal dissection is the method of chioce • Pneumonectomy is done only when Involves proximal bronchus or proximal pulmonary artery Crosses major fissure • Wedge resection is only restricted to persons who are not able to tolerate lobectomy
  • 35. Lymphnode dissection The current minimum standard is a systemic sampling of each lymph node station of tumor Rt sided tumors – 2,3,4,7,8, 9,tracheobronchial angle and interlobar area (10,11) Lt sided tumors – sub aortic, ant med nodes (5,6), 7,8,9
  • 36. Results • 5 yrs survival for patients with Stage I is 65%,Stage II is 60% ,Stage IIIA( N1 disease is 34%,N2 is 24%) • Various studies also concluded that lymphnode dissection is necessary for accurate staging. • Lesser resections like wedge resection result in higher recurrence rate and reduced survival. • Survival is longer in clinical (pre op)N0 or N1 disease but pathological(post resection N2) than clinical N2 disease
  • 37. RADIOTHERAPY Radiation is used in following forms in NSCLC A. AS ADJUVANT * Post Operative * Pre Operative B. PRIMARY RADIATION * Radical * Palliative C. CHEMO-RADIATION NSCLC is a radio responsive tumor but not radiosensitive
  • 38. Role of pre op irradiation • Indications 1. In stage I,II,III tumours • Dose :20 Gy in 5# • Results • Multi institutional trail compared preop RT vs surg alone • No added benefits was found in stage I,II Tumours • But a significant 3 yr survival rate (49.4% vs 28.1%) was observed in stage III
  • 39. Role of Post op RT • Indications 1. Incomplete resection 2. Close or positive margins 3. Positive mediastinal metastases 4. Resected N2 disease 5. Chest wall involvement 6. Superior sulcus tumour • Contraindications 1. Currently contraindicated in patients with stage I completely resected
  • 40. Post op RT(cont…) Dose for potential microscopic Dose for margins positive 60 to disease 50 GY 66 Gy RESULTS TRIALS •PORT Meta Analysis •SEER Database •British Medical Research CONCLUSIONS •Role of PORT in positive N1 disease is controversial •More data supporting role in N2 •The studies used conventional technique •Modern tech like IMRT,3D CRT hopefully will increase the result in favour of PORT
  • 41. Definitive radiotherapy in NSCLC (early stage) INDICATIONS : • 1. Medically inoperable T1-T3 lesions. • 2. Patient refuses surgery. • 3. Critically located lesion. • 4. Non-resectable Stage-II & Stage-IIIA • • 5. Patient with incomplete resection. • 6. Localized recurrent lung cancer.
  • 42. RADIOTHERAPY TECHNIQUES  Conventional External beam radiotherapy • VOLUME 2 cm around the tumour margin • ENERGY 6-10 Mev linac • PORTALS 2 to 3 fields depending on tumour and lymphnodes • DOSE 60-66 GY @1.8-2 GY/#
  • 43.
  • 44. Results of Radiotherapy in early stage • Local control is poor and results are not very encouraging for NSCLC • 5yr local control and overall survival rates ranges from 30 to 50% and 10-30% • Results of conventional RT is certainly inferior when compared with other modality
  • 45. STEREOTACTIC BODY RADIATION THERAPY • SBRT is a combination of multiple beam angles to achieve sharp dose gradients,high precision localisation and a high dose per fraction in extracranial locations. • Delivers a high biologic effective dose BED to target • Minimise normal tissue toxicity • Reduced treatment volume • Reducing treatment time
  • 46. SBRT
  • 47. • Results of SBRT  Image guided SBRT with delivery of BED>100 GY is feasible and produces better results than <100 gy  3 to 5 yr survival rate and local control is much more better than those for conventional RT  For stage I A disease results are comparable with surgery  Emerging as the standard treatment for inoperable stage I NSCLC.
  • 48. Definitive RT In Advanced NSCLC(stage III) • Larger unresectable tumours T4N0-1 or T1-4 N2-3. • Dose given is 60 GY @2GY/# • A higher dose upto 80 to 100 gy is required to improve local control and potential survival but toxicity is main limiting factor here. • However advanced such as 3D crt and imrt have provided a way for dose escalation with out toxicity.
  • 49. non small cell lung cancer newer radiation techniques 1. 3-Dimentional Conformal Therapy. 2. Intensity Modulated Radiation Therapy. 3. IGRT and Gated Radiotherapy. 4. Interstitial Brachytherapy. 5. Endobronchial Brachytherapy. 6. Intra Operative Radiotherapy.
  • 50. 3-D CRT & IMRT IN LUNG CANCER Goal: To increase dose delivery to tumour To minimize dose to normal tissues. Advantages 1. Better conformity of radiation dose to the tumour. 2. Sparing of all the vital structures around tumour. 3. Escalation of dose is possible. 4. Better control of disease. 5. Reduced morbidity.
  • 51. 3-D CRT & IMRT IN LUNG CANCER TREATMENT PLANNING
  • 52. Radiotherapy planning • GTV (Gross Tumor volume) • CTV (Clinical Target volume) • PTV (Planning Target volume) • GTV Visible tumor by any imaging modality including the lesion and lymphnode > 1 cm.
  • 53. RT-Planning – Defining the CTV CTV is the volume that contains gross and microscopic disease A Radiographic histopathologic study demonstrated that CTV varies with histologic type Microscopic extension Adeno Squamos mean value 2.69mm 1.48mm 5mm margin covers: 80% 91% margin to cover 95% 8mm 6mm
  • 54. PTV • One of the important reason of uncertainty in ca lung is motion of the tumor during respirations • PTV is defined as CTV with a margin to account for daily set up error and target motion
  • 55. NON SMALL CELL LUNG CANCER RADICAL RADIATION Image Guided RadiationTherapy-IGRT: It is defined as the use of modern imaging modalities specially those incorporating functional and biological information. 1. To augment target delineation 2. Use of imaging to adjust to target motion and positional uncertainty- respiratory gated therapy 3. Potential to adopt treatment to tumor response.
  • 56. IMAGE GUIDED RADIATION THERAPY EQUIPMENT REQUIRED CT-SCAN MRI PET-CT Linac with on Tomotherapy Cyber knife Board imaging
  • 57.
  • 58.
  • 59.
  • 60.
  • 61. Chemotherapy (NCCN Guidelines 2010) • Indicated in all stages above stage Ib, significant improvement in survival. • First line - Premetrexate + cisplatin is superior to Gemcitabine + cisplatin in non sq cell tumors. - Paclitaxal + carboplatin for sq cell tumors. - Bevacizumab and Erlotinib combined with chemotherapy. - No use of using a third drug in the regime. - Older patients single agent chemotherapy is adviced
  • 62. Second line (in combination with platinum) - Docetaxal - Premetrexate - Irinotecan - Erlotonib • Third line - Erlotinib - Vinorelabine
  • 63. SMALL CELL LUNG CANCER
  • 64. Staging of SCLC Veterans Administration Lung Study Group (VALG) staging system • Limited-Stage Disease (LD SCLC ) - Confined to the hemithorax of origin, the mediastinum, or the supraclavicular nodes, which can be encompassed within a tolerable radiation therapy port. • Extensive-Stage Disease (ED SCLC) - Any disease not meeting limited stage criteria - Distant metastasis. •
  • 65. Staging of SCLC • The International Association for the Study of Lung Cancer (IASLC) revised the VALG classification in accordance with the TNM system. - LD definition is consistent with TNM stages I to IIIB. - ED is limited to patients with distant metastases.
  • 66. Management of SCLC • SURGERY 1. Stage I(T1-2,N0) 2. Lobectomy with mediastinal nodal dissection is the surgery of choice 3. Early stage SCLC is diagnosed in fewer than 5% of SCLC patients,limits the scope of surgery 4. The trial by Medical Research Council led to abandonment of surgery as a primary modality of treatment
  • 67. Combined Chemotherapy and Radiation therapy • Indications 1. To decrease the local recurrence 2. To improve survival 3. Positive lymphnode involvement after surgery
  • 68. Role of Radiotherapy • Meta-analysis by Warde and Payne - 11 prospective trials of chemotherapy with or without RT were analysed - Results : Absolute increase of OS by 5.4 % at 2 years Local control of 25 % with limited stage disease • Pignon et al - 16 randomized studies with 2,140 patients - improvement in abolute survival of 5.4 % at 3 years Definite role for RT in local control of disease which leads to increase in overall survival
  • 69. Role of chemo radiotherapy McCracken et al (154 patients) Results Cisplatin , Etoposide Time Survival & vincristine 2 cycles 2 yr 42 % with RT 1.8 Gy per 4 yr 30 % day upto 45 Gy 5 yr 26 % Concurrent chemo radiotherapy provides good survival advantage with tolerable toxicity to the patient
  • 70. Concurrent Chemoradiation • Advantages 1. Overall shorter treatment time 2. High dose intensity 3. Sensitisation of tumours • Disadvantages 1. Enhanced normal tissue toxicity 2. Treatment breaks 3. Inability to access response to either mode
  • 71. Sequential vs Concurrent chemoradiotherapy Japanese Clinical Oncology Group Arm 1 Paclitaxel 80 mg/m2 on d1 and etoposide 100 mg/m2 d1-3 (2 cycles) Results showed significant improvement of survival in RT 45 GY CRT arm Conclusion:CRT is better Arm 2 than sequential chemo and Paclitaxel 80 mg/m2 on d1 and etoposide radiotherapy 100 mg/m2 d1-3 + RT was started along with chemo from day1
  • 72. Timing of Chemo Radiotherapy • NCI Canada trial 40 Gy in 15 fractions over 3 weeks to the primary site concurrent with the first cycle of EP All 308 eligible patients received (week 3) cyclophosphamide, doxorubicin, and vincristine (CAV) alternating with etoposide and cisplatin (EP) every 3 weeks for three cycles of each late TI patients received chemotherapy regimen. the same radiation concurrent with the last cycle of EP (week 15) Overall survival better in Early RT arm
  • 73. Altered fractionation Turrisi et al Once-daily therapy received 1.8 Gy daily in 25 treatments 417 patients with limited over a period of five weeks. small-cell lung cancer. Patients with a All the patients received four complete response 21-day cycles of Received prophylactic cisplatin 60 mg/m2 and cranial irradiation 25 Etoposide 120 mg/m2 Gy 1n 10 # RT started with CT in first week Accelerated twice-daily thoracic radiotherapy involved the administration of 1.5 Gy in 30 # over a period of three weeks Conclusion : 10% absolute increase in overall survival @ 5yrs with15% increase in high grade esophagitis in Acc RT arm
  • 74. Prophylactic cranial irradiation Metaanalysis conducted in 1999 studied 7 prospectively randomised trail They found a disease free and overall survival advantage in those patients who under went prophylactic cranial irradiation Dose is still a matter of debate however there is a trend in reduction of brain relapses at 36 GY @ 2 GY /# Prophylactic cranial irradiation should be consideredfor complete clinical responders
  • 75. CONCLUSION • NSCLC 1.STAGE I&II  Surgery if feasible followed by adjuvant chemotherapy when indicated  SBRT if not medically fit 2.STAGE IIIA  Surgery with adj chemotherapy + PORT  EBRT with chemotherapy if not fit 3.STAGE IIIB  EBRT with chemotherapy 4.STAGE IV  Chemotherapy with EBRT for palliation
  • 76. CONCLUSION SCLC;Limited disease CONCURRENT CHEMORADIATION IS CONSIDERED • Dose of Radiotherapy should be delivered at 45 GY with1.5 GY/#,twice daily with concurrent Cisplatin and Etoposide. • Prophylactic cranial irradiation should be considered for complete clinical responders. • Patients should be encouraged to participate in newer protocol  Extensive disease • Chemotherapy • Prophylactic cranial irradiation for responders • Palliation

Editor's Notes

  1. *Int journal radnonco 1992-24:11-16