Lung cancer

Lung cancer malignant neoplasm, which leading to death 1.1 million people (each year around the world) most common cause of cancer-related death ! one of the worst prognosis (in oncology)

Lung cancer is the most common cause of cancer deaths in men and women

Cancers in Poland Morbidity women 1. Breast cancer - 24% 2 Cancers in Poland Morbidity women 1. Breast cancer - 24% 2. Lung cancer - 8 % 3. Corpus uteri cancer - 7 % 4. Cervix uteri cancer – 6%

Morbidity men 1. Lung cancer -21% 2. Prostate cancer -12% 3. Bladder cancer – 7% 3. Colon cancer - 6%

Mortality women 2. Breast cancer - 14% 3. Colon cancer - 7% 1. Lung cancer - 15% 2. Breast cancer - 14% 3. Colon cancer - 7% 4. Ovarian cancer – 7%

Mortality men 1. Lung cancer – 32% 2. Prostate cancer – 7% 3. Colon cancer – 7% 4. Stomach cancer – 7%

Diagnosis and prognosis (number of cases diagnosed at each stage and corresponding survival)   Total Cases Percentage of Cases 1-Year Survival 5-Year Survival Stage I 582 14,5% 71,12% 35,33% Stage II 294 7,3% 48,15% 20,89% Stage III 1275 31,8% 34,59% 6,32% Stage IV 1436 35,8% 14,36% 1,51% Stage Not Known 426 10,6% 16,61% 5,79% All Stages 4013 100,0% 32,16% 9,68% Anglia Cancer Network

EPIDEMIOLOGY of LUNG CANCER In Poland (just like the world) is steadily increasing number of cancer patients It is a disease with almost 100% mortality 5-year survivals is about 10 -15 % Lung cancer in Poland ranks first among deaths from cancer in men and women

EPIDEMIOLOGY of lung cancer in Poland Annual total approximately 20 000 new cases of cancers of the respiratory system For example data from 2012 in Poland - registered cancers of the respiratory system: (from „Krajowy Rejestr Nowotworów” - National Cancer Registry) ICD-10 C34 category : Total 21 837 new cases Men 15 177 (70%) Women 6 660 (30%)

Death from lung cancer (in Poland) Weekly with lung cancer die about 400 people It's like every week crashed two airliners

ETIOLOGY The main risk factor for the incidence of lung cancer is smoking, especially cigarettes. The risk of lung cancer in a man burning about 20-30 cigarettes a day for more than 10 years is about 10 times higher than non smoking. Burn >40 cigarettes a day increases the risk to 60 times.

Lung cancer and smoking more than 92% of patients with lung cancer are current or former smokers the remaining few percent are mostly passive smokers, such as those working in smoky rooms or spouses of smokers 10 - 15% of smokers will develop lung cancer

Carcinogens 1. Carcinogens contained in tobacco smoke Polycyclic aromatic hydrocarbons Radioactive isotopes of polonium (Pl210) and carbon (C14) 2. Occupational factors asbestos, silicon, uranium (miners, heavy industry) contact with the dust of iron, arsenic, bismuth, chromium soot, tar, mineral oils (builders of roads, roofers) 3. Environmental factors contact with the products of burning of coal and oil radon 4. Genetic predisposition

Molecular disorders Mutations and overexpression of oncogenes: C-erbB ras myc Loss of tumor suppressor genes: P53 P16 RB

Histopathology of lung cancer (according to WHO 1981) Squamous cell carcinoma 40-60% Adenocarcinoma 10-40% Large cell carcinoma 10% Small cell carcinoma 20%

In clinical practice : Non-small cell lung cancer (NSCLC) - 80% of all patients Small cell lung cancer (SCLC) - 20% of all patients

Clinical signs of lung cancer over a long period of time may be asymptomatic (1-2 years !)

Clinical signs of lung cancer 1. Symptoms caused by the tumor: Cough (alteration its character for dry and tiring) Recurrences of pneumonia Pain/discomfort of chest Hemoptysis Dyspnoea 2. Symptoms of the regional spread of the tumor: Hoarseness (depending on the laryngeal nerve paralysis) Superior vena cava syndrome Dysphagia Horner's syndrome - Pancoast tumor

Horner's syndrome - Pancoast tumor

Superior vena cava syndrome

Superior vena cava syndrome

Clinical signs of lung cancer 3. General symptoms: Weight loss Weakness Elevated body temperature unrelated to infection 4. Paraneoplastic syndromes: Neurological syndromes Endocrine syndromes (e.g. SIADH) Symptoms from connective tissue pulmonary osteoarthropathy clubbed fingers Dermatological symptoms Hematological and vascular symptoms

Paraneoplastic syndrome – clubbed fingers

The diagnosis of lung cancer can be based on cytology or histopathological material from respiratory system

Even the slightest problem with respiratory system in the smoker of cigarettes (more than 10 years) leads to a suspicion of lung cancer

Diagnosis Physical examination Symptoms associated with worsening of airway function Lymph nodes enlargement (especially in the supraclavicular area) Symptoms of the presence of fluid in the pleural cavity Signs of superior vena cava syndrome Liver examination Chest pain (during pressure)

Diagnosis Additional studies Chest X-ray (p-a and lateral) Presence of a circular shadow Changes in the contour of the hilus and/or mediastinum Aeration of lung disorders (emphysema or atelectasis) Infiltrative changes in the lungs Bronchoscopy Cytological examination of sputum, bronchoalveolar lavage, pleural effusion Fine-needle aspiration biopsy Endobronchial Ultrasound (EBUS) Fluorescence bronchofiberoscopy

No changes in x-ray

No changes in x-ray

Diagnosis (more invasive) Videothoracoscopy Mediastinoscopy Thoracotomy

Diagnosis - Staging Studies to determine the stage Physical examination Bronchoscopy Chest X-ray Abdominal ultrasound Computer tomography of chest Mediastinoscopy CT of brain Bone scintigraphy Bone marrow aspiration biopsy of iliac PET

CLINICAL EVALUATION OF STAGING T - tumor N - nodes M – metastases staging → treatment → prognosis

PROGNOSIS IA — 50% 38% IB — 47% 21% IIA — 36% 38% IIB — 26% 18% 5-year survival: IA — 50% 38% IB — 47% 21% IIA — 36% 38% IIB — 26% 18% IIIA — 19% 13% IIIB — 7% 9% IV — 2% 1% NSCLC SCLC

T - tumor From: www.radiologyassistant.nl

T1a T1b

T2a T2b

T3 .

T4

N - nodes From: www.radiologyassistant.nl

N0 N1

N2

N3

M1a

M1b

Clinical Stages of Lung Cancer Stage IA T1 N0 M0 Stage IB T2a N0 M0 Stage IIA T1 N1 M0, T2b N0 M0, T2a N1 M0 Stage IIB T2b N1 M0, T3 N0 M0 Stage IIIA T1 N2 M0, T2 N2 M0, T3 N1 M0, T3 N2 M0, T4 N0 M0, T4 N1 M0 Stage IIIB anyT N3 M0, T4 N2 M0, Stage IV anyT anyN M1 inoperative

PROGNOSIS IA — 50% 38% IB — 47% 21% IIA — 36% 38% IIB — 26% 18% 5-year survival: IA — 50% 38% IB — 47% 21% IIA — 36% 38% IIB — 26% 18% IIIA — 19% 13% IIIB — 7% 9% IV — 2% 1% NSCLC SCLC

Clinical Stages

Karnofsky scale Zubrod scale Before choosing a method of treatment we use the patient's performance scales Karnofsky scale Zubrod scale

Chemotherapy (most cases) Treatment of SCLC Chemotherapy (most cases) PE cisplatin, etoposide CAV cyclophosphamide, doxorubicin, vincristine TOP topotecan Chemoradiotherapy = chemotherapy + radiotherapy (a little better effect but worse tolerance)

Treatment of SCLC Radiotherapy if tumor not respond to the chemotherapy after chemotherapy (as a complement) elective irradiation of the brain (as a prophylaxis)

Effects of chemoterapy

The most effective treatment : operation Treatment of NSCLC The most effective treatment : operation but only about 20% patients eligible Chemotherapy Neoadjuvant chemotherapy (pre-operative) Adjuvant chemotherapy (post-operative) Paliative chemotherapy (most cases)

Treatment of NSCLC Chemotherapy protocols (examples): PN cisplatin, vinorelbine PG cisplatin, gemcytabine DOC docetaxel PEM pemetrexed

New drugs – Target therapy Erlotinib (Tarceva) – cellular tyrosine kinase inhibitor directed against the EGFR (epidermal growth factor receptor) Gefitinib (Iressa) - cellular tyrosine kinase inhibitor directed against the EGFR Bevacizumab (Avastin) – monoclonal antibody that inactivates free VEGF (vascular endothelial growth factor)

Treatment of NSCLC Radiotherapy Radical radiotherapy (CS I-II-IIIA, if surgery not possible) Three-dimensional conformal radiation therapy (3D-CRT) Intensity modulated radiation therapy (IMRT) Stereotactic body radiation therapy (SBRT) Stereotactic radiosurgery (SRS) Paliative radiotherapy – for symptom control: hemoptysis chest pain superior vena cava syndrome dysphagia Post-operative radiotherapy (when neoplasmatic infiltration of the surgical incision line)