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Chest CT for Suspected Pulmonary Complications of Oncologic Therapies: How I Review and Report Stefan Diederich

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Chest CT for Suspected Pulmonary Complications of Oncologic Therapies: How I Review and Report Stefan Diederich Diederich Cancer Imaging (2016) 16:7 DOI 10.1186/s40644-016-0066-4 REVIEW Open Access Chest CT for suspected pulmonary complications of oncologic therapies: how I review and report Stefan Diederich Abstract In cancer patient during or following oncologic therapies with respiratory symptoms and pulmonary pathology at chest CT the differential diagnosis includes infection, therapy-induced disease and tumour progression. Although CT morphology may be typical or even pathognomonic in some conditions the diagnosis is usually made by a synopsis of imaging, clinical and laboratory features. Close communication with referring colleagues and a good knowledge of potential side effects of therapeutic concepts, their time course and CT morphology is crucial in the differential diagnosis. This review describes a personal approach to the radiological diagnosis of therapy-induced pulmonary abnormalities in cancer patients. Keywords: Lung, Radiation pneumonitis, Drug toxicity, Infection, Cryptogenic organizing pneumonia, Oedema, Computed tomography, Image interpretation, Image display Background infectious complications but its toxicity particularly Why imaging for pulmonary complications of oncologic of antifungal therapy may be detrimental in cases of therapy? non-infectious disease. Unnecessary discontinuation In patients during or following therapy for cancer pul- of an effective drug will obviously result in a nega- monary symptoms are common. These may, obviously, tive effect for the patient. be due to a variety of causes such as progression of ma- Furthermore, in cancer patients pulmonary disease lignancy involving the chest as well as infectious or non- may have a more aggressive and potentially lethal course infectious complications of surgery, radiation or medical than in otherwise healthy patients. therapy. In addition, in cancer patients disease unrelated to For all these reasons it is mandatory to establish the malignancy may occur, although the risk for some of these cause of the pulmonary symptoms fast and reliably. conditions may be increased due to the disease or its The clinical signs and symptoms of pulmonary therapy. disease such as cough, dyspnoea, hypoxia and signs The different potential causes of chest symptoms of inflammation are usually unspecific and do not may require completely different therapeutic ap- reliably allow differentiation between the different proaches. Escalation or change of chemotherapy or conditions. molecular therapy may be required in progressive Laboratory test alone are usually not specific enough diseasebutmayhavecatastrophicresultsinpulmon- for patient management. Therefore, imaging is crucial ary toxicity of these drugs. Steroid therapy is usually in these circumstances and has a major impact on indicated in non-infectious inflammatory compli- therapeutic decisions. cations but may aggravate pulmonary infection. This review describes a personal approach to the radio- Antimicrobial treatment is obviously useful in logical diagnosis of therapy-induced pulmonary abnormal- ities in cancer patients. It does not claim to cover all Correspondence: [email protected] aspects of the problem and specifically does not include Department of Diagnostic and Interventional Radiology, Marien Hospital, post-surgical changes. Academic Teaching Hospital, Rochusstr. 2, D- 40479 Düsseldorf, Germany © 2016 Diederich. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Diederich Cancer Imaging (2016) 16:7 Page 2 of 11 Risk considerations: assessing pre-test probability It is relatively easy to make a diagnosis of radiation of different pulmonary complications pneumonitis in simple radiation ports as there is usually As almost all imaging findings in pulmonary complica- a sharp border between involved and normal lung fol- tions are not specific enough to decide on the significant lowing the borders of the radiation port [1,2]. If, how- therapeutic consequences on the basis of imaging results ever, more modern radiotherapy techniques are used alone it is of paramount importance to use a synopsis (e.g. intensity-modulated radiation therapy (iMRT), of clinical laboratory and imaging data to make the gamma-knife, cyber-knife) it may be impossible to estab- diagnosis. lish the diagnosis unless the dose distribution is known (Fig. 1). Ideally, radiation planning data should be avail- Pulmonary disease in oncologic therapy able to the diagnostic radiologist in these patients. Radiation pneumonitis Radiation of pulmonary parenchyma exceeding a dose of Drug-induced pulmonary toxicity 30–40 Gray (Gy) usually leads to radiation pneumonitis A large variety of drugs is used in modern systemic ther- which may be clinically occult but may also present with apy of malignancy and usually combinations of two or symptoms such as unproductive cough, dyspnoea and more drugs are administered in order to increase the ef- clinical and laboratory signs of inflammation. ficacy without increasing toxicity. Classical cytotoxic Radiation pneumonitis follows a rather typical time chemotherapy, leading to cell tumour necrosis may be course: 6–10 weeks after the radiation dose threshold combined with molecular therapy that blocks cell me- has been exceeded ground glass is observed which then tabolism, blood supply and other cellular functions with- increases in density to present as consolidation. After out actually destroying the tumour cells. Most recently some months fibrosis occurs with a decrease in volume immune therapy has been introduced in which the host’s of the involved lung area and signs such as traction immune response to the malignant cells is enhanced [3]. bronchiectasis and displacement such as interlobar fis- Many of these agents have side effects that may sures, vessels and bronchi. manifest in the lung. Due to the fact that there are Radiation pneumonitis almost exclusively involves the innumerable combinations of different drugs with differ- lung area that was affected by radiation dose above the ent doses it is very difficult to predict potential toxic ef- threshold and is not limited by anatomical borders such fects in the lung. Furthermore, the spectrum of drug- as interlobar fissures. induced pulmonary disease is not unique but represents Fig. 1 Radiation pneumonitis. Patient with NSCLC (non-small cell lung cancer) treated with radiation. a Dose distribution at radiation planning simulation. b Chest CT at lung window with consolidation. Note the tongue-like area of consolidation in the anterior segment of the left upper lobe reflecting the area with > 75 % of the total dose at the dose distribution plan Diederich Cancer Imaging (2016) 16:7 Page 3 of 11 a spectrum of diseases which also occurs unrelated to Other disease with increased risk in cancer patients drug toxicity. Cryptogenic organizing pneumonia (COP) manifests It includes hypersensitivity pneumonitis, interstitial as solitary or multiple peripheral areas of consolidation, pneumonitis with a pattern of non-specific interstitial pulmonary nodules or masses, peribronchovascular con- pneumonia (NSIP) (Fig. 2), cryptogenic organizing pneu- solidation or other morphology. monia (COP), pulmonary haemorrhage, pulmonary It may occur secondary to infection, therapy with dif- oedema, bronchiolitis, vasculitis and many others. ferent drugs, collagen vascular diseases or with no Finally, one drug may cause several different patterns known cause (idiopathic COP). of pulmonary toxicity. Therefore, it is almost impossible In cancer patients it may be a manifestation of drug- to know all possible patterns of drug-induced lung disease induced lung disease. It is also associated with radiation even in the commonest therapeutic regimens. There is a therapy. Other than radiation pneumonitis the lung ab- very helpful freely available website which lists all potential normalities are not confined to the radiation port and effects of a large variety of drugs (not only in oncology) the time course is variable with COP occurring weeks or which is regularly updated (http://www.pneumotox.com). months after radiation therapy [4]. The website does not present radiological images but lists Deep venous thrombosis (DVT) leading to pulmon- potential patterns. ary embolism (PE) is more common in cancer patients than in patients with no malignancy. It may be due to the cancer (e.g. particularly increased risk in pancreatic Infection: predisposing factors for infection with different cancer) or its therapy (e.g. antihormonal therapy in hor- organisms mone receptor-positive breast cancer) [5]. Obviously, immunosuppression due to malignancy Pulmonary oedema is not uncommon in patients (e.g. lymphoma, leukaemia) or its therapy (particularly undergoing chemotherapy as many regimens include chemotherapy, molecular therapy) often increases the large amounts of fluid in order to decrease the local tox- risk of pulmonary infection. icity of the drugs. Particularly in patients with renal Furthermore, depending on the affected cell line and insufficiency this
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