Pulmonary Complications of Cancer Treatment

Transcription

1 Pulmonary Complications of Cancer Beth Zigmund, MD Objectives (Preliminary Version) Beth Zigmund, MD Develop awareness of the myriad pulmonary complications of cancer treatment and of challenge in making correct diagnosis Describe Radiation and Chemotherapy Induced Complications Radiation Induced Complications: Radiographic Patterns Conventional wisdom Challenges of current delivery techniques Chemotherapy Induced Pulmonary Complications Patterns of injury Challenges of novel therapies Radiation Induced Pneumonopathy Chemotherapy Induced Pneumonopathy Surgical Infectious : Community aquired, Atypical, Aspiration Pulmonary emboli Radiation Induced Pneumonopathy Chemotherapy Induced Pneumonopathy Surgical Infectious : Community aquired, Atypical, Aspiration Pulmonary emboli Lung Cancer Other Cancers Lung Cancer Other Cancers 313

2 Elevated Risk in the Lung Cancer Patient Primary neoplasm is pulmonary: lung surgery primary curative modality Underlying lung disease Mean age more advanced: ~70% diagnosed at 65 years of age or greater* Decreasing tissue mass Impaired drug clearance Greater number of co morbidities *Ries LAG et al. SEER Cancer Statistics Review Cost of Better s Aim to lengthen survival, improve palliation Multimodality, multiregimen treatment now standard Surgery Chemotherapy Radiation therapy Mounting New, escalating respiratory symptoms Recurrence or Progression Recurrence or Progression Drug Diagnostc Quandry Radiation Drug Diagnostc Quandry Radiation (Case Example) Radiation Induced Radiotherapy indicated in about 64% of NSCLC patients overall: ~46% initially, 18% later in illness Radiotherapy indicated in about 54% of SCLC patients overall: 45% initially, 9% for recurrence or progression Tyldesley S et al. Estimating the need for radiotherapy for lung cancer: an evidence based, epidemiologic approach. Int J Radiat Oncol Biol Phys 2001; 49:

3 Radiation Therapy Risks Irradiation of normal lung major dose limiting factor Typical dose: 60 to 70 Gy to tumor and local nodal metastases Invariably some damage to normal lung Threshold for pneumonitis ranges from 5 to 20 Gy 50 90% of patients undergoing lung irradiation develop radiographic or pulmonary function abnormalities * Mechanism still not well understood *Tsoutsou et al. Int J Radiat Oncol Biol Phys. 2006: 66(5): Factors Influencing Risk Volume of normal lung irradiated Cumulative dose Size of fractions delivered, schedule of delivery fractions schedule delivery Comcomitant chemotherapy: certain agents in particular Previous Irradiation: lowers threshold Genetic factors? Radiation Induced Lung Stages of Injury Improving geometric accuracy of delivery systems conformal RT intensity modulated RT Complications have not been eliminated. Ex: Pneumonitis reported in 5 15% of patients receiving external beam radiation therapy for lung cancer Acute, exudativeexudative stage : Radiation pneumonitis 0 2 months after treatment Steroid responsive Organizing, proliferative stage: Radiation pneumonitis 2 9 mo after treatment Steroid responsive Chronic, fibrotic phase: Radiation fibrosis > 9 mo after treatment, stable after 24 mo Not steroid responsive; supportive therapy Radiologic Manifestations: The Conventional Wisdomisdom (Clinical Case Image slides) Conventional RT (Clinical Example Image Slide) Geographic margins Confined to the radiation portal 315

4 (Current RT Techniques: Image Slides) Chemotherapy Induced Complications Direct Effects Chemotherapy Induced Complications Drug : A Difficult Diagnosis Direct effects of therapy: Incidence ranges from 1 to 30%, depending on agent Direct Effects Overlap: Intercurrent infection, progression of tumor, fluid overload, pulmonary edema, pulmonary embolism Multidrug regimens: Difficult to ascribe to a particular agent Nonspecific radiologic findings, multiple patterns Less frequent than radiation toxicity, but can be florid and may have higher mortality rate Consult with referring clinician! (Image slide case example) Agents (NSCLC and SCLC) well described in certain established agents: mitomycin, bleomycin Novel chemotherapeutic agents Antimetabolites: gemcitabine Taxanes: paclitaxel, docetaxel Topoisomerase I Inhibitors: topotecan, irinotecaninhibitors: topotecan irinotecan Topoisomerase II Inhibitors: etoposide Tyrosine Kinase EGFR Inhibitors: erlotinib, gefitinib Vascular Endothelial Growth Factor Inhibitor: bevacizumab Combination regimens now the standard for both SCLC and NSCLC Clinical trials continue to reveal toxicity profiles of various combination regimens Higher response rates may be offset by greater toxicity 316

5 Class Agents Observed Toxicities Class Agents Observed Pulmonary Toxicities Platinum Agents Taxanes Cisplatin Carboplatin Paclitaxel Docetaxel Minor except when used in combination NSIP, Interstitial Fibrosis, HP, DAD, Capillary Leak Edema, Eosinophilic Pneumonia Platinum Agents Taxanes Cisplatin Carboplatin Paclitaxel Docetaxel Minor except when used in combination; various patterns in combination regimens NSIP, Interstitial Fibrosis, HP, DAD, Capillary Leak Edema, Eosinophilic Pneumonia Antimetabolites Gemcitabine NSIP, Interstitial Fibrosis, DAD, DAH, Veno occlusive Disease Tyrosine kinase EGFR Inhibitors Topoisomerase Inhibitors Gefitinib Erlotinib Etoposide Topotecan Irinotecan Monoclonal Antibodies Bevacizumab DAH DAD, DAH NSIP, Bronchiolitis Obliterans, DAD Antimetabolites Gemcitabine NSIP, Interstitial Fibrosis, DAD, DAH, Veno occlusive Disease Tyrosine kinase EGFR Inhibitors Topoisomerase Inhibitors Gefitinib Erlotinib Etoposide Topotecan Irinotecan Monoclonal Antibodies Bevacizumab DAH DAD, DAH NSIP, Bronchiolitis Obliterans, DAD Dimopoulou I, Bamias A, Lyberopoulos P, et al. Pulmonary toxicity from novel antineoplastic agents. Ann Oncol 2006 ; 17: Dimopoulou I, Bamias A, Lyberopoulos P, et al. Pulmonary toxicity from novel antineoplastic agents. Ann Oncol 2006 ; 17: (Image slides various patterns, various agents) Pulmonary Drug : Remove offending agent Steroids Supportive treatment Summary (Case Example Image Slide) Summary Long differential diagnosis in cancer patient with respiratory complaints, lung cancer patient in particular Radiation Therapy: continued challenge despite challenge despite improvements in delivery techniques, confusing radiologic patterns Chemotherapy: wide spectrum of abnormalities, challenge posed by new agents and combination regimens 317

6 Key References Spiro SG, Douse J, Read C, et al. Complications of Lung Cancer. Semin Respir Crit Care Med 2008; 29: Park KJ, Chung JY, Chun MS, Suh JH. Radiation induced lung disease and the impact of radiation methods on imaging features. Radiographics 2000; 20: Dimopoulou I, Bamias A, Lyberopoulos P, et al. Pulmonary toxicity from novel antineoplastic agents. Ann Oncol 2006; 17: Abeloff M et al. Abeloff s Clinical Oncology, 4 th Edition. Philadelphia: Churchill Livingstone,