Dr. György Losonczy Professor and chairman Department of Pulmonology Semmelweis University Clinical oncology special course 2017.
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1 Dr. György Losonczy Professor and chairman Department of Pulmonology Semmelweis University Clinical oncology special course 2017.
2 Symptoms of lung cancer Cough (2/3rd of patients have) Haemoptoe (½ of patients) Chest pain (1/3-1/2, pleura, thorax, mediastunum) Wheezing, stridor tomorous obstruction of central airways Dyspnea Pancoast-syndrome: cancer at the apex, spreads into neighbouring tissues (Bone, nerve, vessel, spine, severe shoulder pain) Hoarseness (paresis of n. laryngeus recurrens) Paresis of the diaphragm (n. phrenicus) Vena cava superior-syndrome Bone pain (metastasis) Neurologica symptoms (brain metastasis) Paraneoplastic syndromes
3 Examinations in suspicion of lung cancer Physical, special emphesis: hyperpigmentation, erythema, lymphatic glands (!), percussion, auscultation, blood pressure, pulse General state of patient: called performance state e.g. Zubrod-scale: 0 normal activity 1 can walk, but needs support 2 spends in bed close to 50% of time 3 more than 50% of daylight hours in bed 4 bed-ridden Laboratory: chemistry, hematology, tumor markers Radiology: X-ray + CT (PET, MRT)
4 Vena-cava superior syndrome cancer patient swollen neck chest skin red / cyanotic swollen veins on chest wall
5 Frequent paraneoplastic syndromes Deep venous thrombosis-pulmonary embolism Cachexia Neutrophilia, thrombocytosis, lymphopenia, anaemia Overproduction of hormones: ADH (hyponatraemia), ACTH,etc. Hypertrophic osteoarthropathy ( drumstick-finger ) Neuropathy, myasthaenia Encephalopathy, dementia Symptoms of paraneoplastic syndromes can preceed by years the clinical evidence of cancer.
6 Drumstick-fingers in lung cancer
7 Chest X-ray: Pancoast-tumor (before and after chemotherapy)
8 Adenocarcinoma in the right upper lobe with accumulation of pleural fluid (stage IV.) Survival 6 months
9 PET-CT image of left paravertebral lung cancer, claviculo-scapular osseal metastasis
10 Pericardial metastasis of lung cancer: pericardial tamponade, puncture and removal of pericardial fluid, cytological test: P5 adenocellular lung cancer PERICARDICENTESIS P5 cytol. adenocc. met.
11 Bleeding bronchial carcinoma blocking the orifice of right main bronchus and deforming the bifurcation 262-es
12 Transbronchial biopsy of lung cancer
13 Histological types of lung cancer Small cell lung cancer (15%) Non small cell lung cancer (85%) Adenocarcinoma large cell carcinoma Squamous carcinoma Adenosquamosus carcinoma Carcinoid (typical, atypical)
14 Stages (I-IV.) and operability according the stage of lung cancer T1-4 N1-3 M0-1 T N M Stage I (A,B): <T2 0 0 Stage II (A,B): <T3 <1 0 curable Stage IIIA: <T4 <2 0 operable (resectable) Stage IIIB: T4 N3 0 non-operable Stage IV: any any 1 not curable
15 N1 and N2 (if ipsilateral) and N3 (if contralateral) lymph nodes infuencing staging of lung cancer
16 Definitions in cancer treatment Curative treatment: eradicates cancer, cures patient (surgery, irradiation) Palliative treatment: induces regression of cancer, does not eradicate it, patient will not be free of cancer (chemotherapy, targeted therapies) Supportive treatment: completes curative and palliative treatments, attenuates side effects, toxicities of curative and palliative treatments (supports the treatment not the patient) Symptomatic treatment: reduces symptoms of cancer patients (this is not equal with palliation or supportation).
17 Treatment of lung cancer Small cell lung cancer (any stage): not curable, radiochemotherapy, very rarely curable - surgery (T1-2, N0, M0 with PET) Non-small cell lung cancer: Stage I-IIIA: curable, surgery (resection), or irradiation Stage IIIB-IV: not curable, radiochemotherapy, including molecularly targeted and immune therapies
18 Surgical treatment Open thoracotomy Videoassisted (endoscopic) surgery Radicality of resection Pulmonectomy Bi-lobectomy Lobectomy Wedge resection
19 Role of radiation therapy in treatment of lung cancer More than 50% lung cancer patients need irradiation therapy, but irradiation is curative only in about 20%. The other 30% receives palliative irradiation. Curative, if: N0 M0 Potentially curative, if: N1-3 + M0 Palliative, if: M1 Small cell lung cancer: chemotherapy is central Non-small cell: radiochemotherapy is central
20 Treatment of small cell lung cancer Curative in early stage ( limited disease (LD) <IIIA) Combined with Cisplatin/etoposid chemotherapy consolidating irradiation increases local control of cancer growth and prolongs survival 45 Gy on primary lung tumor and mediastinum Prophylactic whole brain irradiation is indicated in limited disease after completing local cancer treatment and reaching remission.
21 Treatment of non-small cell lung cancer: stage IA-IIB Resection +/- Irradiation Lobectomy or bi-lob/pulmonect. (pn0-1) Resection of smaller than a lobe Tumor resectable, patient inoperable not indicated curative postop. radiochemoth. curative, definitive radiochemotherapy
22 Treatment of non-small cell lung cancer: stage IIIA-IV. Lung surgery + Irradiation Removable T1-3 and pn2 (stage IIIA.) curative postop. irrad. or chemoth. Removed T1-3, non-removed N2 Explored, but irresectable T/N (IIIB.) In stage IV, removable T1-3 if M1 is controlled palliative postop. radiochemother. palliative radiochemo. palliative/symptomatic radiochemo.
23 Chemotherapy of inoperable lung cancer Chemotherapy is palliative. Cytostatic agents impede function of DNA of fast mitotic tissues (not only in cancer!) Platinum+etoposid Platinum+gemcitabin Platinum+taxan Platinum+navelbin Platinum+pemetrexed
24 The antiangiogenic bevacizumab (Avastin) added to platinum doublets and administered as a maintanance therapy Bevacizumab: monoclonal antibody of vascular endothelial growth factor (high inside cancer): prolongs progression-free survival, improves quality of life and overall survival. Only in adenocarcinoma if no risk of bleeding (local and in distant organs apoplexy!)
25 Main targets of biological therapy in cancer tyrosine kinase domain
26 2010: gefitinib vs carbo+pacli in 1st line, in EGFR mutant stage IV. adenocarcinoma (Maemondo. NEJM 2010) Carbo-pacli
27 Stage IV. adenocarcinoma: before (A), 10 months (B) and 16 months after (C) gefitinib A B C
28 Inhibition of immune checkpoints CTLA-4 and PD-1 Lymph nodes Microenvironment of the tumor Dendritic Cell MHC B7 TCR CD B7 CTLA Anti-CTLA-4 Activation (Cytokines, lysis, proliferation, migration to the tumor) T cell CTLA-4 signaling pathway T cell TCR PD-1 MHC PD-L1 Anti-PD-1/PD-L1 PD-1 PD-L2 Anti-PD-1 Tumor cell PD-1 signaling pathway CTLA-4 regulates the amplitude of the earlier activation of naive and memory T cells. PD-1 limits the T-cell activation in the periphery during an inflammatory reaction.
29 Anti-PD-1 monotherapy vs docetaxel in squamous lung cancer, second line(brahmer et al. NEJM 2015)
30 Supportive and symptomatic treatment of lung cancer patients Pain relievers Colony-stimulating factors (G-CSF, erythropoietin) Fluid-electrolyte balance Treatment of comorbidities: COPD, ischemic heart disease, hypertension, depression, etc. Psychologic and social support Physician s role during last months, weeks, days and hours.
31 Ratios according treatment Chemotherapy total 50% Irradiation total 17% chemo+irr.9% Irr.6% Only symptomatic 32% only chemo.31% surg+chem.8% only surg.12% surg+irr+chemo 2% Resection total 22%
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