lung cancer staging and management

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an overview of assessment and treatment of lung cancer

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” رب اشرح لى صدرى ₪ ويسر لى أمرى ₪ واحلل ₪ عقدة من لسانى يفقهوا قولى ‟ بسم الله الرحمن الرحيم صدق الله العظيم ( طــه 25،26،27،28)

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LUNG CANCER : STAGING , TREATMENT AND METASTASIS By Dr. Mahmoud Alsalahy Assist prof of Chest Medicine Banha University, Egypt

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STAGING Defines extent of disease spread Assessed by TNM system: › T umor size, › Lymph N ode spread, › Distant M etastasis Determines resectability Operability depends on general status + resectability

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TNM STAGING

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TNM STAGING contd.

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(15)% (1-5%) (15)% (5%)

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Mediastinal LN stations (ATS)

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Mediastinal LN stations (ATS)

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Karnofsky’s performance scale (detailed)

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Karnofsky’s performance scale (applied) 80-100% 70-50% 40-0% Withstands pneumonectomy Only withstands lobectomy or segmentectomy Cant withstands surgery

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TREATMENT Depends on: Cell type: NSCC or SSC Disease stage: resectable or not General conditions: tolerability of surgery Associated comorbidity: an end stage chronic disease present or not

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TREATMENT contd. NSCC: Stage I: Patient is operable : Pneumonectomy, lobectomy or segmentectomy with mediastinal LN sampling Patient is inoperable (or refuses surgery) : Curative radiation therapy: 13-39% 5 year survival Stage II: As stage I + adjuvant chemotherapy for operable patients Stage IIIA: Surgery plus adjuvant (neo or post) chemo-therapy. Bulky N1 and N2: concurrent or sequential chemoradiotherapy Stage IIIB: Chemoradiotherapy: concurrent is better Stage IV: Palliative

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TREATMENT contd. Outcome: NSCC : Stages IA and IB : 5-year survival of 67% and 57%, respectively Stages IIA and IIB : 5-year survival of 55% and 39%, respectively Stage IIIA : 5-year survival of 26 % Stage IV : no 5 year survival, < 2 years SCC: mainly chemotherapy Only 5% of limited disease are amenable to surgery Outcome: Only 15% to 20% of these patients with limited disease survive 3 years (consider PCI)

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PARANEOPLASTIC SYNDROMES

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Paraneoplastic syndromes are clinicopatho -logic syndromes not due to direct or distant spread and mediated by humoral factors Musculoskeletal Cutaneous

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Endocrinologic Neurologic Less common

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Vascular Hematologic

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1. Endocrinopathies: Cushing’s syndrome: Due to excess CRH or ACTH and its precursors Most common with SCLC (75%) Clinically : weakness, trunkal obesity, thin skin, hyperglycemia, hypokalemic alkalosis Diagnosis: ACTH > 200 pg /ml, 24 hrs free urine cortisol elevated Treatment: Adrenal enzyme inhibitors: metyrapone (250-750 mg, tds /d oral), aminoglutethemide (250 mg/d oral), ketoconazol (400-1200 mg/d oral) Good response in few weeks, may → hypofunction Chemotherapy or resection Indicates a poor prognosis

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Endocrinopathies contd. 2. Hypercalcemia: 2.5% of BC Most common with squamous cell type Mechanism: ectopic PTHrP , bony metastasis, prostaglandins, osteoclast activation Clinically: weakness, polyuria, polydipsia, vomiting, constipation, nephrolithiasis, abdominal pains, arrhythmias, dehydration Treatment: Rehydrate if pt is dehydrated : 3-6 L/ 24 hrs Mild cases (<12mg/dl) and severe cases (>20 mg/dl) are not treated Bisphosphonate ( Zolidronate , Zometa ): 4mg/15 min IV/d (10-40 days); inhibits bone resorption Calcitonin: weak but rapid onset (4-6 hrs ), additive to bisphosphonate Resection or chemotherapy

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3 . Inappropriate ADH secretion: Most common with SCLC (75%) Mechanism: excess vasopressin secretion Clinically: Mild: Symptoms of hyponatremia Severe: Brain edema: irritability, personality changes, confusion, seizures, coma Diagnosis: Hyponatremia, increased urine Na (>20mEq/L) urine/serum osmolality > 2 Treatment: Mild: Fluid restriction: 500-1000 ml/day Moderate-severe: Demeclocycline: 900-1200 mg/day Endocrinopathies contd.

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With any cell type Mechanism: unknown humoral factors, neurogenic Clinically: Finger clubbing: connective tissue deposition in distal phalanges Hypertrophic osteoarthropathy (HPO): new bone formation at the end of long bones with painful swelling: = May be the presenting feature = May resolve spontaneously after thoracotomy Polymyositis-dermatomyositis: inflammation in skeletal muscles and skin (15-25% have malignancy) Diagnosis: X-ray and bone scan: subperiosteal bone formation, skin & muscle biopsy Treatment: NSAD, Bisphosphonate 2 . Musculoskeletal:

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3 . Neurologic effects: Most common with SCC Mechanism: Immune mediated: ↑ANNA1&2, ↑CRMP-5 Clinically: Somatic neuropathy: peripheral neuropathy, encephalo -myelopathy, cerebellar and retinal degeneration, myopathy Autonomic neuropathy: hypotension, GIT disturbances Eaton –Lambert syndrome: proximal myopathy, hyporeflexia plus autonomic neuropathy: ↑anti VGCC antibodies (90%) May present months before tumor detection Associated with LD and better outcome Resolve with therapy Diagnosis: clinical picture + ↑antibodies + axon action pot Treatment: Diaminopyridine: ↑acetyl choline release

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4 . Hematologic effects: With any cell type Mechanism: cytokines Clinically: Anemia : common Thrombocytosis: : most common and most important with recurrent DVT (Trousseau ´s syndrome) Leukocytosis and eosinophilia Diagnosis: clinical picture + CBC + clotting profile Treatment: Fractionated heparin (LMWH) Vit K antagonists: not effective

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5 . Dermatologic effects: With any cell type Mechanism: cytokine mediated Clinically: Hypertrichosis languinosa: fine silky hairs esp on face and ears Leser-Trelat sign : abrupt development of seborrheic keratosis Acanthosis nigricans: bilateral symmetrical hyperpigmen-tation with hyperkeratosis especially in flexures Erythema gyratum repens : erythematous bands making parts of circles Dermatomyosistis Diagnosis: clinical picture Treatment: of the tumor

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SECONDARY TUMORS (METASTASIS)

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Are deposits of primary tumors originating outside the lungs Lung metastasis is common: 20-40% of all malignancies May be synchronous or metachronous Metastasis is not a simple filter impaction effect but 2 main mechanisms help settling of malignant cells in the lungs: 1. Cytokine directed trafficking: = Lungs: contain ligands CXCL12 & CCL21 that attract breast cancer cells (rich in receptors of these ligands : CXCR 4 & CCR 7) = Dermis: contains CTACK & CCL27 ligands that attract CCR 10 receptors extensively expressed on malignant melanoma cells 2. Induction of cytotoxic cytokines that disrupts tight junctions in pulmonary capillary endothelium: TFG-F in breast cancer cells induce ANGPL4 protein These new facts opens the concepts for new therapies that can prevent metastasis

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Clinical picture: Asymptomatic: commonly Usually detected during clinical evaluation: as a solitary or multiple nodules on X-ray That of local effects ( as 1ry BC ) Picture of 1ry malignancy D.D: see next

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DIFFERENTIAL DIAGNOSIS OF PULMONARY METASTAIS ON X -RAY Clinical differential diagnosis depends on symptoms and clinical signs

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Investigations: As in primary BC: 1. Radiologic: Single or multiple nodules commonly in lower lobes CT, PET, PET-CT and SPECT are very helpful CT guided biopsy: 65-75% sensitivity for lesions < 1cm and > 90% for those > 1.5 cm (35% risk of pneumothorax) 2. Pathologic: usually difficult than BC 3. Biochemical: important to determine the origin 4. Bronchoscopy: important but of less value than in BC

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Volume rendering CT

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PRIMARY OR SECONDARY: A biopsy may not be necessary when a patient with a history of prior cancer presents with lung nodules with highly typical characteristics: (1) History of a cancer likely to metastasize to the lungs ( 2) Multiple (3) New (or growing), ( 4) lower lobe pulmonary nodules ( 5) Smooth borders. (6) Measurable serum markers ( CA19-9, CA125, CEA, alpha-fetoprotein, ß-human chorionic gonadotropin , CYFRA21-1 ) especially if rising

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PRIMARY OR SECONDARY: Sometimes impossible, especially in adenocarcinoma Biopsy (usually surgical) + immunohistochemical staining Molecular methods: gene classifiers; recent

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Bronchoscopy in lung metastasis: Of great help but much less than BC In peripheral lesions: < 20% yield Three-dimensional CT reconstruction combined with electromagnetic navigation probe through an extended working channel has allowed biopsy of small peripheral lung nodules with significa-ntly greater accuracy (80%) Combining this technique with real-time imaging using a radial probe ultrasound catheter to confirm the location suggested by virtual images further increased the accuracy of transbronchial biopsy to 88%

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EBU classification of lung nodules (92% benign) (99% Malig ) (99% Malig )

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Electro magnetic navigation steerable probe

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3D electromagnetic navigation aided with ultrasound for bronchoscopic sampling of a small peripheral lesion

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TREATMENT OF METASTASIS: Depends on: Nature of primary tumor Extent of primary tumor General condition of the patient Associated comorbidities Includes: Surgical resection Radiofrequency ablation Multimodality treatment Palliative

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TREATMENT OF METASTASIS contd. Surgical resection: Complete resection of all deposits is essential Can be repeated when possible Need careful evaluation of number and sites Best is by open thoracotomy but can be done by VATS if peripheral Best results are seen in tumors with preferential metastasis to the lung: ○ Osteogenic and soft tissue sarcoma ○ Colorectal cancer ○ Uterine cancer ○ Head and neck cancer ○ Breast cancer ○ Testicular cancer ○ Renal cell tumors ○ Malignant melanoma

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Criteria for application of surgical metastatectomy

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Outcome of surgical metastatectomy

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Radiofrequency ablation (Thermoplasty): Is the use of radiofrequency frictional heat and cell death Better results in: Lesions < 3 cm Surrounded by lung tissue Away from central structures Multiple lesions can be treated at one setting but cant treat both sides at the same time The main risk is pneumothorax (50%)

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Multimodality treatment: Depending on the primary Treat primary in the right way e.g. chemotherapy Residual lung metastasis is treated by surgery or thermoplasty Example: testicular cancer is best treated by chemotherapy and residual lung metastasis can be resected Palliative care: For patients with incurable disease different modalities can be used to control symptoms

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