Response assessment of response to treatment in the cancer patient: a tutorial for the radiologist

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1 Response assessment of response to treatment in the cancer patient: a tutorial for the radiologist Poster No.: C-0755 Congress: ECR 2016 Type: Educational Exhibit Authors: O. Catalano, A. Nunziata, V. Granata, R. Fusco, V. Nunziata, A. Petrillo ; Naples/IT, Ercolano/IT, L'Aquila/IT Keywords: Diagnostic procedure, Treatment effects, Ultrasound, MR, CT, Oncology, Cancer DOI: /ecr2016/C-0755 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 44

2 Learning objectives This exhibit is intended as an illustrated guide to improve the assessment of patients undergoing cancer treatment, with special reference to the knowledge of the Response Evaluation Criteria in Solid Tumors (RECIST) system version 1.1 (Fig. 1 on page 3). In this exhibit we: highlight the importance of tumor measurement describe the main modalities of tumor measurement illustrate the main tips and tricks in the radiological assessment and reporting of measures illustrate the main dimensional systems in the assessment of response to treatment, with special emphasis on the RECIST 1.1 mention the limitations of purely dimensional assessment, indicating other possible systems. Page 2 of 44

3 Images for this section: Fig. 1 free internet image Page 3 of 44

4 Background Tumor extent influences staging, treatment planning, and prognosis of cancer patient. The measurement of lesions size consequently represents a key moment in oncologic imaging. Measuring cancer lesions is relevant for several reasons (Fig. 2 on page 5): size is a key aspect in establishing the T staging parameter of most cancers tumor size and tumor-to-organ size influences the surgical planning size is a key aspect in defining a cancer as locally advanced (for example in the breast) and consequently in deciding for a neoadjuvant treatment current oncological criteria in establishing the response to treatment of the lesions are based on their number and size size correlates with patient prognosis. Serial sizing is fundamental in the objective assessment of tumor response to treatment, influencing the oncologist's decision making (Fig. 3 on page 5). Page 4 of 44

5 Images for this section: Fig. 2 Pubmed downloaded Page 5 of 44

6 Fig. 3: Lung adenocarcinoma. Serial scanning. Diameters before and during chemotherapy Page 6 of 44

7 Findings and procedure details Obtaining cancer measures The ideal measurement modality should be accurate, obtaining the measures in a quick and simple but at the same time reproducible (no intraobserver and interobserver variation) manner. There are various different modalities of measurement (Fig. 4 on page 10). The golden rules for measuring cancer at diagnostic imaging are the followings: scroll the images to find the slice with the largest cross-sectional tumor extent track the largest diameter using the electronic calipers track the largest diameter perpendicular to the first one (mandatory for WHO criteria but desirable aside from the response assessment criteria employed) use special care for ill-defined, infiltrating tumors include any tumor digitation or spiculation avoid including encompassed normal parenchyma avoid including host changes (fibrosis, desmoplastic reaction, perifocal edema, atelectasis, perifocal hyperemia, etc.) avoid including any visible in situ tumor component. Several technical issues may affect the measurement and this is of special relevance when comparing serial studies from the same patient. We suggest the following golden rules: consider patient position and posture possibly use axial images for measurements consider that slice thickness may influence measurement be aware that dose energy does not influence measurement (low dose scanning!) consider that the window setting may influence measurement (Fig. 5 on page 10), (Fig. 6 on page 11). consider that choice between 2D and 3D MRI acquisition may influence measurement consider that the acquisition phase may influence measurement (use the arterial phase for hypervascular lesions and the venous phase for hypovascular ones) be aware that measurement discrepancies between different imaging modalities and between imaging and pathology are known to occur (Fig. 7 on page 12). Page 7 of 44

8 The tumor area is a 2D measurement. Tumor contour is tracked on the image with the large tumor cross-sectional extent and the area is calculated automatically. This modality is employed rarely. The tumor volume is a 3D measurement. Nowadays volumetric measures are obtained using semiautomatic softwares, seem to be more reproducible than any 2D measurement. Reporting cancer measures We suggest to: use millimeters write always the largest diameter first and the perpendicular diameter then (e.g. 24x17 mm) save on the PACS an image with the measurements tracked or indicate in the report the number of sequence and image employed for measurements debate with the oncologist which lesions consider for future post-treatment assessment. The largest lesions are not necessarily the best one to be chosen as targets for follow-up look at the images form patient's previous studies and do not rely exclusively on the previous report if a lesion splits into separate fragments after treatment, add the diameters of each fragment if two or more lesions coalesce after treatment, measure the diameters of the merged mass read the measures at the end of writing the report. Assessing tumor response to treatment To date, systems based on linear size measurement are the only one accepted worldwide in oncology practice. Size changes are fundamental for the oncologist's decision making. Size stability or reduction means "continue with the same treatment strategy" while size increase means "change the treatment strategy" (Fig. 8 on page 13). Basically there are two standardized systems employed to assess the response to chemotherapy, WHO and RECIST (Fig. 9 on page 14), (Fig. 10 on page 15), (Fig. 11 on page 16). Recently a new version of the RECIST system has been published, the ver RECIST 1.1 make some relevant changes and clarifies some undefined aspect of the former version (Fig. 12 on page 17), (Fig. 13 on page 18), (Fig. 14 on page 19). RECIST 1.1 system must be regarded as the current standard in the dimensional assessment of tumor response to chemotherapy (Fig. 15 on page 20). Page 8 of 44

9 While assessing and measuring the tumor burden, the radiologist must be aware that there are lesions being truly not measurable. These include Leptomeningeal disease, ascites, pleural/pericardial effusion, inflammatory breast disease, lymphangitis cutis/ pulmonis, abdominal masses that are not confirmed and followed by imaging techniques (Fig. 16 on page 21). Bone lesions are regarded as nonmeasurable according to RECIST. Instead, bone lesions are considered measurable in RECIST 1.1 proven they have a soft tissue component meeting the criteria for target lesions (Fig. 17 on page 22). Cystic and necrotic lesions are regarded as nonmeasurable according to RECIST. Cystic and necrotic lesions are instead considered measurable in RECIST 1.1 if they meet the criteria for target lesions (Fig. 18 on page 23). However, pure solid lesions should be preferred whenever available. Going beyond the size The WHO and RECIST systems were developed in the era of conventional chemotherapy using cytotoxic agent. These systems may not allow early assessment of tumor response, particularly for newer cancer therapies (angiogenesis inhibitors, target drugs, immunotherapy, radioembolization, chemoembolization, tumor ablation, etc.). The treatments have the tendency to inactive the tumor lesions but their collapse is frequently slow and partial (Fig. 19 on page 24), (Fig. 20 on page 25), (Fig. 21 on page 26). There are two ongoing strategies to encompass limitations linked to of dimensional systems. The first one is to use new systems of tumor response assessment based on functional information (purely functional or mixed functional and morphological) (Fig. 22 on page 27), (Fig. 23 on page 28), (Fig. 24 on page 29), (Fig. 25 on page 30), (Fig. 26 on page 31). The second option is to use new, quantitative imaging modalities (Fig. 27 on page 32), (Fig. 28 on page 33). Page 9 of 44

10 Images for this section: Fig. 4: Various different modalities of measurement Page 10 of 44

11 Fig. 5: Lung epidermoid carcinoma. Diameter taken with two different window settings Page 11 of 44

12 Fig. 6: Lung epidermoid carcinoma. Diameters taken with two different window settings Page 12 of 44

13 Fig. 7: Breast carcinoma. Diameters measured at US and MRI. Pathologic correlation Page 13 of 44

14 Fig. 8: Left liver lobe metastasis from colon cancer. Appearance before and after chemotherapy Page 14 of 44

15 Fig. 9: WHO and RECIST: Major differences Page 15 of 44

16 Fig. 10: Calculation of tumor burden (three lesions) according to bidimensional (WHO) and monodimensional (RECIST) systems Page 16 of 44

17 Fig. 11: CT scan of the chest in a 62-year-old man with a spiculated nodule in the anterior segment of the right upper lobe (metastatic-stage NSCLC before and after treatment) Page 17 of 44

18 Fig. 12: RECIST and RECIST 1.1: Major differences Page 18 of 44

19 Fig. 13: Categorization of response to chemotherapy according to RECIST systems. Target lesion/s Page 19 of 44

20 Fig. 14: Categorization of response to chemotherapy according to RECIST systems. Non-target lesion/s Page 20 of 44

21 Fig. 15: Response assessment to chemotherapy according to RECIST 1.1 system Page 21 of 44

22 Fig. 16: Lesions truly not measurable Page 22 of 44

23 Fig. 17: Bone lesions measurement in RECIST 1.1 Page 23 of 44

24 Fig. 18: Cystic and necrotic lesions are considered in RECIST 1.1 Page 24 of 44

25 Fig. 19: Hepatocellular carcinoma. Appearance before and after percutaneous radiofrequency ablation Page 25 of 44

26 Fig. 20: Lung metastasis from colon cancer. Appearance before and after chemotherapy Page 26 of 44

27 Fig. 21: Lung epidermoid carcinoma. Appearance before and after chemotherapy Page 27 of 44

28 Fig. 22: Alternative systems to assess tumor response Page 28 of 44

29 Fig. 23: Liver metastases from colon cancer. Attenuation measured before and after chemotherapy Page 29 of 44

30 Fig. 24: Renal clear-cell carcinoma and malignant inferior vena cava thrombosis. Size and attenuation measured before and after chemotherapy (target therapy with sunitinib) Page 30 of 44

31 Fig. 25: Liver metastases from colon cancer. Diameter and attenuation measured before and after therapy (folfox + bevacizumab) Page 31 of 44

32 Fig. 26: Liver metastasis from colon cancer. Diameters and attenuation measured before and after chemotherapy Page 32 of 44

33 Fig. 27: Alternative imaging modalities to assess tumor response Page 33 of 44

34 Fig. 28: Locally-advanced rectal cancer. Appearance before and after neoadjuvant chemo-radiotherapy Page 34 of 44

35 Conclusion Correct measurement of cancer lesions and appropriate knowledge of the treatment response assessment systems is mandatory in radiological practice. The radiologist must be aware of the tips and trick for a perfect size measuring, even if knowing that morphology does not reflect always adequately the tumor response to newer therapies. Page 35 of 44

36 Images for this section: Fig. 1 free internet image Page 36 of 44

37 Personal information Orlando Catalano, MD, Dept of Radiology I, National Cancer Institute, Pascale Foundation, Naples, Italy Antonio Nunziata, MD, Radiology, Private institute, Naples, Italy Vincenza Granata, MD, Dept of Radiology I, National Cancer Institute, Pascale Foundation, Naples, Italy Roberta Fusco, Biomedical Engineer, Dept of Radiology I, National Cancer Institute, Pascale Foundation, Naples, Italy Vittoria Nunziata, L'aquila University, L'aquila, Italy Antonella Petrillo, MD, Dept of Radiology I, National Cancer Institute, Pascale Foundation, Naples, Italy Page 37 of 44

38 Images for this section: Fig. 29 National Cancer Institute, Pascale Foundation, Naples, Italy Page 38 of 44

39 Fig. 30 National Cancer Institute, Pascale Foundation, Naples, Italy Page 39 of 44

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