Lung Cancer- ......mediastinal mass.pptx

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1. Lung Cancer BY- Dr. Azinkya Joshi (Assistant Professor)

2. Introduction It is the leading cause of cancer death in the world and It is the second most commonly diagnosed cancer. Most frequently diagnosed in 65 to 74 years. More in male smokers. 5 year survival rate: 10-20% ( due to late diagnosis)

3. Etiological factors Tobacco and Lung Cancer: Most important modifiable risk factor for lung cancer. Depends on age of starting, number of cigarettes per day, tar content and type. Contain 5300 chemicals and around 70 carcinogens.

4. Harmful constituents in cigarettes: Nicotine : Addictive property , not carcinogenic TAR : Carcinogenic Benzopyrene Polycyclic Aromatic Hydrocarbons (PAH) : Benzene N-nitrosamines 1-3 Butadiene Cadmium Tobacco Specific N-nitrosamine (TSNA) Cause DNA damage – DNA adducts Defective DNA repair – Lead to mutation Epigenetic mechanism like : DNA methylation, histone deacetylation. P53, BRAF, KRAS : Mutations more in smokers

5. Lung Cancer in Non-Smokers Non-Smoker: Those who have smoked <100 cigarettes in lifetime. More common in women, younger age, adenocarcinoma Mutations in Chromosome 13: Glypican-5 alterations. Mutation in TERT ( Telomerase Reverse Transcriptase) EGFR, ROSI, ALK mutations. Better survival with targeted therapy Mainstream smoke is produced by inhalation of air . Side stream Smoke is produced from smouldering of cigarette between puff- is a major source of second hand smoke through the burning cigarette.

6. Risk factors in non-smokers: Environmental tobacco smoke ( mainstream+ side stream smoke). Air pollution. Comorbid lung disease Occupation Exposures Scleroderma: scar carcinoma (adenoma) Underlying Lung conditions: Increase risk in COPD and TB : Chronic inflammation ILD (IPF) : Repeated lung injury, epithelial mesenchymal transition Chlamydia pneumonia and HIV : Association with lung cancer cases have been reported. Human herpes virus-8, HPV, Epstein-Barr virus

7. Occupational exposure and air pollution: Asbestos, arsenic , beryllium, cadmium, chromium, nickel, silica. Asbestos: Mesothelioma and Lung cancer Radon is a domestic indoor air pollutant. PM2.5 and sulphur oxide: Carcinogenic Combustion of fossil fuels and Diesel exhaust.

8. Selected Occupational Carcinogens and Associated Exposures

9. Pathogenesis Lung cancer results from the dysregulation of cellular processes that control cell cycling and death, allowing unrestricted cell growth and Growth-promoting pathways that promote NSCLC include activating mutations in tyrosine kinases such as EGFR, ALK, ROS1, BRAF, MET, and RET. Activating mutations in intracellular guanosine triphosphatases (GTPases) such as KRAS. The identification of a variety of molecular and genetic alternations in NSCLC has provided the opportunity for targeted, personalized therapy, such as EGFR TKIs for activating EGFR mutations in NSCLC, ROS1 inhibitors for NSCLC expressing ROS1 fusions, and ALK inhibitors for NSCLC harboring ALK rearrangements.

10. Clinical features of Lung Cancer Symptoms elicited in History: Cough Dyspnea Haemoptysis Chest pain Constitutional- weight loss >10lb Musculoskeletal- focal skeletal pain Neurologic- headache, syncope, seizures, extremity weakness, recent change in mental status

11. Signs found on physical examination: Lymphadenopathy(>1cm) Hoarseness Superior vena cava syndrome Bone tenderness Hepatomegaly (>13cm span) Focal neurologic signs, papilledema Soft tissue mass

12. Lung Cancer Screening Chest radiography and sputum cytology -lung cancer screening tools LDCT(Low Dose CT) : As a screening test given its higher sensitivity to detect small tumors. LDCT could detect more lung nodules and early stage lung cancers than CXR. LDCT scans that revealed any non -calcified nodule measuring at least 4 mm in diameter and CXR images that revealed any non-calcified nodule or mass were classified as positive

13. Lung CT Screening Reporting and Data System (LUNG-RADS) for Screen-detected Nodules

14. Lung CA Classification Lung carcinomas are classified according to the best differentiated component, and pathologists assign a degree of differentiation to tumors that show differentiation, such as squamous cell carcinoma and adenocarcinoma. This is also known as histologic grading , and it is used in tumor pathology as a way of attributing prognostic significance to a specific histologic pattern.

15. LUNG CANCER CLASSIFICATION Small Cell Lung Cancer Non Small Cell Lung Cancer Others Squamous Cell Ca. Adenocarcinoma 1.Atypical Adenomatous Hyperplasia 2.Adenocarcinoma in-situ 3.Minimally invasive Adenocarcinoma 4.Invasive non-mucinous Adenocarcinoma 5.Invasive mucinous Adenocarcinoma Large cell carcinoma Adeno-squamous carcinoma

16. Others type of lung cancers- Carcinoid Tumors- Typical carcinoid Atypical carcinoid Salivary gland Tumors- Adenoid Cystic carcinoma Mucoepidermoid carcinoma Epithelial-Myoepithelial Carcinoma Large cell Neuroendocrine carcinoma

17. TNM Staging System for Lung Cancer

18. LUNG CANCER LYMPH NODE MAP

19. Targeted Therapy in Advanced Non–Small-Cell Lung Cancer Treatment

20. Radiotherapy for NSCLC

21. Definitive RT For Early-stage, Inoperable NSCLC Surgical resection for early-stage NSCLC- Gold standard of care for patients with stage I disease. Patients with early-stage NSCLC are elderly and have significant lung disease, heart disease, and/or other relative or absolute Contraindications to thoracic surgery. “Medically inoperable” patients can be cured with RT alone. Their prognosis with respect to the lung cancer is significantly better than that for patients with stage III/technically inoperable NSCLC

22. Contraindications of Radiotherapy

23. MEDIASTINAL MASSES AND THYMOMA

24. The mediastinum is the region in the chest between the pleural cavities that contain the heart and other thoracic viscera except the lungs Boundaries Lateral - parietal pleura Anterior - sternum Posterior - vertebral column and paravertebral gutters Superior - thoracic inlet Inferior - diaphragm

25. Anterior mediastinum Everything lying forward of and superior to the heart shadow Boundaries Sternum, first rib, imaginary curved line following the anterior heart border and brachiocephalic vessels from the diaphragm to the thoracic inlet Contents Thymus gland, substernal extension of the thyroid and parathyroid gland and lymphatic tissues

26. Middle mediastinum Dorsal to the anterior mediastinum, extends from the lower edge of the sternum along the diaphragm and then cephalad along the posterior heart border and posterior wall of the trachea Contents Heart, pericardium, aortic arch and its major branches, innominate veins and superior vena cava, pulmonary arteries and hila, trachea, group of lymph nodes, phrenic and upper vagus nerve

27. Posterior Mediastinum Occupies the space between the back of the heart and trachea and the front of the posterior ribs, and paravertebral gutter It extends from the diaphragm cephalad to the first rib Contents Esophagus, descending aorta, azygos and hemiazygos vein, paravertebral lymph nodes, thoracic duct, lower portion of the vagus nerve and the symphathetic chain

28. The  Superior Mediastinum  is that portion of the interpleural space which lies between the manubrium sterni in front, and the upper thoracic vertebrae behind. It is bounded below by a slightly oblique plane passing backward from the junction of the manubrium and body of the sternum to the lower part of the body of the fourth thoracic vertebra, and laterally by the pleurae.

29. DD of Mediastinal Masses

30. DIAGNOSIS Biopsy : If a patient presents with atypical features or is found to have an invasive tumor and is under consideration for induction therapy, obtaining preoperative biopsy is indicated. The limited anterior mediastinotomy (Chamberlain approach) is the standard approach that typically is performed over the projection of the tumor . A thoracoscopic approach for biopsy also can be used

31. DIAGNOSIS Chest CECT scan is the imaging procedure of choice in patients with MG. Thymic enlargement should be determined because most enlarged thymus glands on CT scan represent a thymoma . CT scan with intravenous contrast dye is preferred to show the relationship between the thymoma and surrounding vascular structures, to define the degree of its vascularity , and to guide the surgeon in removal of a large tumor , possibly involving other mediastinal structures 

32. PROGNOSIS Benign tumors are noninvasive and encapsulated . Conversely, malignant tumors are defined by local invasion into the thymic capsule or surrounding tissue. The Masaoka staging system of thymomas is the most commonly accepted system. Preponderance of evidence indicates that all thymomas , except completely encapsulated stage 1 tumors , benefit from adjuvant radiation therapy The prognosis of a person with a thymoma is based on the tumor's gross characteristics at operation, not the histological appearance.

33. SURGERY TWO TECHNIQUES: 1. OPEN MEDIAN STERNOTOMY. 2. VIDEO ASSISTED THORACOSCOPIC SURGERY ( VATS) The preferred approach is a median sternotomy providing adequate exposure of the mediastinal structures and allowing complete removal of the thymus,

34. If the tumor is small and appears readily accessible, perform a total thymectomy with contiguous removal of mediastinal fat. If the tumor is invasive , perform a total thymectomy in addition to en bloc removal of involved pericardium, pleura, lung, phrenic nerve, innominate vein, or superior vena cava . Resect one phrenic nerve; however, if both phrenics are involved, do not resect either nerve, and debulk the area. Clip areas of close margins or residual disease to assist the radiation oncologist in treatment planning

35. Radiotherapy Adjuvant radiation therapy in completely or incompletely resected stage III or IV thymomas is considered a standard of care. The use of postoperative radiation therapy in stage II thymomas has been more questionable. Thymomas are indolent tumors that may take at least 10 years to recur; therefore, short-term follow-up will not depict relapses accurately.

36. Chemotherapy The most common chemotherapy drugs in the treatment of thymoma are: doxorubicin ( Adriamycin , Rubex ), cisplatin ( Platinol ), cyclophosphamide ( Cytoxan , Neosar ), etoposide ( VePesid , Etopophos , Toposar ), and ifosfamide ( Ifex , Holoxan ). The common combinations used for the treatment of thymoma include: cyclophosphamide , doxorubicin, and cisplatin , or etoposide and cisplatin .