lung cancer Gloria R. Cristal-Luna, M.D.

Transcription

1 lung cancer Gloria R. Cristal-Luna, M.D.

2 LUG Cancer Algorithm for the Diagnostic and Evaluative Process in Bronchogenic Carcinoma CPM 1 ST EDITIO 1 Lung CA suspect 2 3 Chest x-ray positive for solitary lesion? Solitary pulmonary lesion Figure Are palpable nodes/masses present? Biopsy positive? Radiation chemotherapy or both 7 8 Other masses Assessment of lung CA Figure 3 Figure 1 See specific treatment depending on histopathologic diagnosis 367

3 CPM 1 ST EDITIO 1 LUG Cancer Solitary Pulmonary odule 2 3 Calcified? Observation* 4 on-calcified Review of previous x-rays possible? odule stable? Treat accordingly 8 9 odule enlarging or nodule not previously present eedle biopsy Metastatic? Total body scan positive? Medical Treatment 13 Thoracotomy Indeterminate?** LTS* benign? Observation Figure Malignant? Thoracotomy * Lesion is probably benign ** Thoracotomy may also be performed for indeterminate lesions + LTS - lung tissue sample See specific treatment depending on histopathologic diagnosis 19 Benign granuloma 20 Treat accordingly 368

4 LUG Cancer CPM 1 ST EDITIO 1 Assessment of lung CA 2 Sputum, FOB* positive? 3 FAB** positive? 4 Thoracoscopy Mediastinoscopy Mediastinotomy positive?+ 7 5 Small cell CA? 6 assess stage Figure 4 on-small cell CA Figure TB, fungus present? Treat accordingly egative result Patient is high risk Surgery Figure 3 * FOB - fiber optic bronchoscopy ** FAB - fine needle aspiration biopsy + May also do VATS (video-assisted thoracic surgery) 369

5 CPM 1 ST EDITIO 1 LUG Cancer SCLC* 2 Hx, PE, CXR, CT Chest Staging work-up CT brain Biochem, Screening profile TBBS** LFTs+, BMAB++ euron Specific Enolase 3 4 Limited disease/ T1T2? Chemotheraphy + Radiotherapy Extensive disease responsive patient (80% or more)? Follow-up Disease free >3 y (10-15%) Observation Chemotherapy Salvage Tx Responsive patient (60-70%)? Follow-up Disease free (1%)? Observation Treat accordingly on-responsive (30-40%)? Progressive Disease (99%) 18 Salvage therapy Figure 4 * SCLC - small cell lung carcinoma ** TBBs - total body bone scan + LFTs - liver function tests ++ BMAB - bone marrow aspiration biopsy 370

6 LUG Cancer 1 CPM 1 ST EDITIO SCLC* 2 History, PE, CT Chest LFTs**, TBBS + if clinically (+): CT head abdominal CT Lumbar puncture Stage I? ++ Medically operable? Surgery 6 Radiotherapy with curative intent 7 8 Stage II? ++ Surgery 9 Stage IIIA? eoadjuvant Chemotherapy ± Radiotherapy Surgery 12 Post-op Radiotherapy adjunctive chemotherapy on clinal trials Stage IIIB? ++ Radiotherapy + Chemotherapy Surgery if w/ partial/complete responses Stage IV ++ Chemotherapy Radiotherapy Supportive Care Figure 5 * SCLC - non-small cell lung carcinoma ** LFTs - liver function tests + TBBs - total body bone scan ++ Refer to p. 376 for TM staging 371

7 CPM 1 ST EDITIO Guidelines for the Treatment of Lung Cancer LUG Cancer Introduction The pathology of lung cancer starts in the bronchial epithelium. It usually develops from the epithelium of the primary and segmental bronchi and less frequently from the peripheral bronchi. Epidemiology A. Incidence Most frequent cancer in the world. Most frequent cancer among men in most European countries and the United States of America. Rapidly increasing among women. More than 800,000 people die annually worldwide. Incidence also rising in developing countries. Most common type of cancer among Filipino males (65.4 per 100,000 ASR), 3rd among females (18.7 per 100,000 ASR), most frequent site in both sexes combined. - male/female ratio = Average age - standardized incidence rate for both sexes per l Incidence rate in the Philippines is slightly higher than in Japan and Thailand but lower than in Hong Kong, Europe and the USA. Rates for Filipino migrants to Hawaii, USA were slightly higher than that in the Philippines, while those of Filipino migrants to Los Angeles were slightly lower. B. Risk Factors Tobacco and cigarette smoking. Passive smoking or second hand smoker. Chemicals arsenic compounds asbestos alkylating agents as mechlorethamine hydrochloride bis-chloromethyl ether chromium compounds mustard gas (sulfur mustard) nickel compounds soots tars Ionizing some mineral oils radiation (x-rays and radon) Screening for high risk individuals: age > 40 years old, smokers, passive smokers) Chest x-ray yearly or every 6 months Sputum cytology, yearly or every 6 months Diagnosis A. Clinical Signs and Symptoms of Carcinoma of the Lung: 1. Peripheral tumor (most often adenocarcinoma or large cell undifferentiated carcinoma): Pain from pleural or chest-wall involvement Cough Dyspnea on a restrictive basis Lung abscess from tumor cavitation 2. Central tumor (most often epidermoid or small cell undifferentiated carcinoma): Cough Hemoptysis Wheezing and stridor Dyspnea from obstruction Pneumonias from obstruction (fever and productive cough) 3. Regional spread: Superior vena caval syndrome (SVC) from vascular obstruction Recurrent laryngeal nerve paralysis with hoarseness Phrenic nerve paralysis with elevated hemidiaphragm and dyspnea Sympathetic nerve paralysis with Homer's syndrome Pancoast's syndrome with ulnar pain from eighth cervical and first thoracic nerves Tracheal obstruction Esophageal obstruction with dysphagia Pericardial and cardiac failure, tamponade, arrhythmia Pleural effusion from lymphatic obstruction Lymphangitic tumor spread with hypoxemia and dyspnea 4. Paraneoplastic syndromes: Endocrine Ectopic PTH and hypercalcemia (epidermoid) Inappropriate ADH and hyponatremia (small cell) Ectopic ACTH and Cushing's syndrome (small 372

8 LUG Cancer cell) Carcinoid syndrome Gynecomastia Hyperglycemia Hypoglycemia Galactorrhea TSH secretion Calcitonin secretion Peripheral Clubbing (all cell types) Hypertrophic pulmonary osteoarthropathy and periostitis (adenocarcinoma) eurologic/muscular Eaton-Lambert, myasthenic syndrome (small cell) Peripheral neuropathy (sensory motor) Subacute cerebellar degeneration Polymyositis Myelopathy Dementia Psychosis Cardiovascular Migratory thrombophlebitis (Trousseau's syndrome) onbacterial thrombotic (marantic) endocarditis Arterial thrombosis Hematologic (adenocarcinoma) Disseminated intravascular coagulation (DIC) Iron deficiency anemia Hemolytic anemia Red cell aplasia Polycythemia Thrombocytopenic purpura Eosinophilia Dysproteinemia Constitutional Symptoms Anorexia, cachexia Cutaneous Dermatomyositis Acanthosis nigricans Pruritus Urticaria Hyperpigmentation Erythema multiforme Renal ephrotic syndrome Glomerulonephritis Hyperuricemia Amyloidosis 5. Metastatic tumor spread Central nervous system involvement Liver involvement Bone and bone marrow involvement Other involvement B. Laboratory Diagnostics Minimum - Sputum cytology chest X-ray FOB-PLB(PAB) lymph node biopsy Pleural fluid cytology Optional - CT scan VATS Mediastinoscopy Thoracoscopy Bone scan Bone marrow biopsy lung biopsy Pathological Classification I. EPITHELIAL TUMORS A. Dysplasia and Carcinoma-in-situ B. Malignant CPM 1 ST EDITIO 1. Squamous cell carcinoma (epidermoid carcinoma) a. Spindle cell (squamous) carcinoma variant 2. Small cell carcinoma a. Oat cell carcinoma b. Intermediate cell type c. Combined oat cell carcinoma 3. Adenocarcinoma a. Acinar adenocarcinoma b. Papillary adenocarcinoma c. Bronchiolo-alveolar carcinoma d. Solid carcinoma with mucus formation 4. Large cell carcinoma a. Giant cell carcinoma variant b. Clear cell carcinoma variant 5. Adenosquamous carcinoma 6. Carcinoid tumor 7. Bronchial gland carcinomas a. Adenoid cystic carcinoma b. Mucoepidermoid carcinoma c. Others 8. Others 373

9 CPM 1 ST EDITIO Staging I. O-SMALL CELL CARCIOMA Definition of TM PRIMAR TUMOR (T) TX Primary tumor cannot be assessed, or tumor proven by the presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy. TO o evidence of primary tumor. Tis Carcinoma in situ. Tl Tumor 3 cm or less in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus)*. T2 Tumor with any of the following features of size or extent: More than 3 cm in greatest dimension; Involves main bronchus 2 cm or more distal to the carina; Invading the visceral pleura; Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung. T3 Tumor of any size that directly invades any of the following: chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura, or parietal pericardium; or tumor in the main bronchus less than 2 cm distal to the carina but without involvement of the carina; or associated atelectasis or obstructive penumonitis of the entire lung. T4 Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, esophagus, vertebral body, carina; or tumor with a malignant pleural effusion**. Regional Lymph odes () * The uncommon superficial tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classified as T1. ** Most pleural effusions associated with lung cancer are due to tumor. However, there are a few patients in whom multiple cytopathologic examinations of pleural fluid are negative for tumor. In these cases, fluid is non-bloody and is not an exudate. When these elements and clinical judgement dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging element and the patient should be staged as T1, T2, or T3. LUG Cancer X Regional lymp nodes cannot be assessed 0 o regional lymph node metastasis 1 Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, including direct extension 2 Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s) 3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s) DISTAT METASTASIS (M) MX Presence of distant metastasis cannot be assessed MO o distant metastasis Ml Distant metastasis STAGE GROUPIG Occult TX O MO Stage 0 Tis O MO Stage I Tl O MO T2 O MO Stage II Tl 1 MO T2 1 MO Stage IIIA Tl 2 MO T2 2 MO T3 O MO T3 1 MO T3 2 MO Stage IIIB Any T 3 MO T4 Any MO Stage IV Any T Any Ml II. SMALL CELL LUG CACER LIMITED DISEASE: The limited disease classification includes patients with disease restricted to one hemithorax with regional lymph node metastases including hilar, ipsilateral and contralateral mediastinal, &/or supraclavicular nodes. In addition, patients with ipsilateral pleural effusion are included, independent of whether the cytology is positive or negative. The inclusion of the contralateral nodes in the mediastinum and the supraclavicular region was decided because the prognostic influence of these metastatic sites is less than that of distant metastases, & also because the revised TM system groups these patients in stage III and not in stage IV. Stage I - III of the revised TM then offers a subdivision of the limited disease category, which may be useful when local treatment modalities are evaluated. EXTESIVE DISEASE: The extensive disease classification includes all patients with disease sites not eligible for the limited stage, and this category is equivalent to stage IV of the TM system. 374

10 LUG Cancer Treatment I. Treatment options for SCLC (on-small cell lung carcinoma) A. SURGER I Lobectomy II Lobectomy or pneumonectomy III A Lobectomy, chest wall resection III B With succeeding neoadjuvant treatment I-II and with poor pulmonary reserve-segmentectomy or wedge resection done through video-assisted thorascopy B. CHEMOTHERAP Active agents: Platinum Paclitaxel compounds Ifosfamide Gemcitabine etoposide Vinorelbine Vindesine Cyclophosphamide Docetaxel Adriamycin eoadjuvant treatment for SCLC: C3 etoposide, CDDP MMC, Ifosfamide, CDDP Sequential: CTX x 2 - RT - CTX x 6 cyclophosphamide adriamycin cddp concurrent: CDDP-RT alternating: CTX-RT Split-Course: cgy - CTX cgy II. Treatment for SCLC (small-cell lung carcinoma) Limited disease: confined to the chest, mediastinal, supraclavicular nodal regions ± pleural effusion Extensive disease: metastasis outside local chest region Active Agents: Cyclophosphamide adriamycin Vincristine cddp etuposidc A. RADIOTHERAP Type: 1. Teletherapy- Cobalt linear Accelerator 2. Brachytherapy CPM 1 ST EDITIO 6000 cgy >6 weeks at 200 cgy daily to primary tumour cgy to regional lymph nodes: weeks II. Adjuvant - post-operative (+) hilar or mediastinal lymph nodes (+) lines of resection cgy weeks at 200 cgy daily fraction III. eoadjuvant - pre-operative cgy weeks followed by surgery and post-operative radiotherapy IV. Palliative 1. IIIB or IV with distressing symptoms 2. Metastatic sites cgy in 2-3 weeks V. Combined Modality 1. Sequential : adjuvant CTX-RT followed by CTX induction CTX followed by RT 2. Concurrent : simultaneous RT and CTX 3. Alternating : CTX and RT 4. Split-Course : CTX in between courses of RT Prognosis I. on-small Cell 5-year survival rate early Stage 70% Overall after surgery 20% unresectable with RT 5% WD squamous cell longer large cell & Adeno Shorter Carcinoma Stage 5-year survival rate 0 with surgery curable I with RT 20-30% II with surgery 25-50% Stage 2 and 3 year survival rate IIIA with surgery 25% +15% IIIA with neoadjuvant ctx 60% and 50% IIIB and IV Significant Palliation II. Small Cell 2 years 3 years 5 years limited disease 8.5% 10% 10-20% with CTX extensive disease 2.2% 3-5% I. Definitive or Curative (Radiotherapy alone) a. Medically inoperable Stage I and II b. Locally advanced unresectable Stage IIIA and IIIB 375

11 CPM 1 ST EDITIO Drugs Mentioned in the Treatment Guideline LUG Cancer The following index lists therapeutic classifications as recommended by the treatment guideline. For the prescriber's reference, available drugs are listed under each therapeutic class. Cyclophosphamide Cyclophar... l0l Cvytoxan... l0l Endoxan-Asia... l0l Docetaxel Taxotere...P* Etoposide Lastet Vepeside Ifosfamide Holoxan Paclitaxel Taxol Vincristine DBL Vincristine Sulfate Inj Delta West- Vincristine Inj Vincristine Richter Vincristine- Pharmachemie