Imaging Cancer Treatment Complications in the Chest

Transcription

1 Imaging Cancer Treatment Complications in the Chest Michelle S. Ginsberg, MD Objectives Imaging Cancer Treatment Complications in the Chest To understand the mechanisms of action of different classes of chemotherapeutic agents cytotoxic agents classic cytostatic - molecularly targeted To learn to recognize pulmonary and cardiovascular complications of both classes of chemotherapies Classic Chemotherapy Agents Molecular Targeted Agents Molecular Targeted Therapies Cetuximab Trastuzumab Bevacizumab Rituximab EGFR or VEGFR 237

2 EGFR Inhibitors: Mechanism of Action Monoclonal antibodies Cetuximab Panitumumab EGFR TKIs Erlotinib Gefitinib mtor Everolimus Temsirolimus Protein synthesis cell growth Angiogenesis Proliferation EGFR/HER family receptor Antiapoptosis Metastasis Arteaga. Semin Oncol. 2003;30:3; Wheatley-Price. Curr Opin Oncol. 2008;20:162. Adapted from Ritter CA, Arteaga CL. Semin Oncol. 2003;30(suppl 1):3-11. Pulmonary Infiltrates: most common cx of classic and new target tx Hemorrhage Cardiovascular Cardiotoxicity PAH HTN Pericardial Effusion Diffuse air-space disease/ground glass opacities (most common) Pulmonary edema - due to overhydration Capillary-leak syndrome increased vascular permeability : inflammatory reaction of alveolar capillary wall Noncardiogenic pulmonary edema can lead to ARDS in late stages Diffuse interstitial disease severe alveolar wall damage fibrosis Most Typical Appearance Diffuse Ground Gass Opacities Classic Cytotoxic Drugs 10% of patients develop drug-induced lung reactions Ground-glass attenuation Focal areas of consolidation Interstitial pneumonitis and fibrosis Predominantly involve the lower zones Peribronchial or subpleural areas of consolidation 238

3 Bleomycin Bleomycin induced pulmonary toxicity Presents 1-6 months after treatment initiation 3-6% of patients taking the drug Progressive dyspnea Cryptogenic organizing pneumonia (COP) Eosinophilic hypersensitivity Interstitial pneumonitis progressing to fibrosis High FiO2 intra or post op exposure increases risk of ARDS Conjoint radiation increases risk Used in HD, squamous and testicular cancers 32 y.o. Tx for NSHD on Bleomycin Bx- PCP Oxaliplatin Presents 3-6 months after treatment initiation Progressive cough and dyspnea Rapidly progress to fibrosis and some to fatal pneumonitis Used in colorectal cancer Docetaxel Newer Agents Docetaxel Gemcitabine Paclitaxel Akira M, Ishikaw ah, Yamamoto S. Drug-induced Pneumonitis: Thin- Section CT Findings in 60 Patients. Radiology 2002; 224:

4 Docetaxel Breast cancer patient; low grade fevers for several weeks Used in lung, ovarian, breast and head and cancer Gemcitabine Treatment of NSCL and also other solid tumors; pancreas, and ovarian Reticulo-nodular interstitial infiltrates nonspecific finding Capillary-leak syndrome: Tx: Discontinuation of the drug Steroids Diuretics Vasculitis Associated with Gemcitabine Rare complication: reactive vasculitis in supra-aortic vessels De Pas T, Curigliano G, Franceschelli L, et al. Gemcitabine-induced systemic capillary leak syndrome. Ann Oncol Nov;12(11): Stenosis Left SCA Stenosis Right BCA 240

5 Bevacizumab (Avastin) Monoclonal Antibodies Bevacizumab Cetuximab Rituximab Trastuzumab Monoclonal antibody against vascular endothelial growth factor (VEGF) Angiogenesis inhibitor Approved for use in metastatic colon cancer and NSCLC Squamous cell histology- exclusion criteria Tyrosine Kinase Inhibitors Erlotinib Gefitinib Imatinib Sorafenib Sunitinib 241

6 EGFR TKI Pulmonary Toxicity Etiology poorly understood Suggested repair of epithelial cells requires activation of EGFR-mediated pneumocytes which is inhibited CT: ground glass opacities most common Highest mortality: air space consolidation- rep diffuse alveolar damage with hyaline membrane formation Gefitinib (Iressa) Acute onset of dyspnea + cough May present 1 week 1 month after initiation of treatment Sometimes fatal Approx. 1% of patients worldwide Cohen MH, Williams GA, Sridhara R, et al: FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets. Oncologist 2003; 8: Erlotinib (Tarceva) Erlotinib pulmonary toxicity 6 weeks later Asymptomatic Patient on Sunitinib 1 month later 12 weeks later 242

7 Everolimus (mtor) inhibitor Temsirolimus (mtor) inhibitor 13.5% clinically identified pneumonitis weeks after starting tx Sx: cough and dyspnea, some fever and fatigue etiology of the pneumonitis remains speculative? hypersensitivity mechanisms appears be dose dependent in some individuals radiographic patterns; variable ground-glass infiltrates to diffuse infiltrates patterns frequently changing over time White DA, et al. Noninfectious Pneumonitis after Everolimus Therapy for Advanced Renal Cell Carcinoma. Am J Respir Crit Care Med Aug 1;18 (3): Everolimus (mtor) Induced Pulmonary Toxicity Everolimus (mtor) Noninfectious Pneumonitis 243

8 Asymptomatic on mtor Inhibitor 1 month later Cardiomyopathy Classic agents: anthracyclines and alkylating Vascular Arterial thromboembolic: anti-angiogenic/vegfr-targeted therapy Mechanism unknown? maintenance of integrity vascular endothelium Venous thrombosis: Gemcitabine and Cisplatin Arterial Hypertension Anti-angiogenic agents due to inhibition of VEGFR pathway 244