Analysis and Interpretation of Perfusion CT in Oncology: Type of Cancer Matters

HomeRadiologyVol. 292, No. 3 PreviousNext Reviews and CommentaryFree AccessEditorialAnalysis and Interpretation of Perfusion CT in Oncology: Type of Cancer MattersValentin Sinitsyn Valentin Sinitsyn Author AffiliationsFrom the Department of Radiology, Medical Faculty of Lomonosov, Moscow State University, Lomonosovsky prospect 27/1, Moscow 119991, Russia.Address correspondence to the author (e-mail: [email protected]).Valentin Sinitsyn Published Online:Jul 9 2019https://doi.org/10.1148/radiol.2019191265MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In See also the article by Hamdy et al in this issue.IntroductionFor many years, perfusion CT has been used for assessment of the brain and myocardial circulation in clinical settings. However, the use of perfusion CT for oncologic indications is quite different. Limitations of anatomic-morphologic approaches based on grading of tumor size and volume dynamics are well known. After the launch of new types of anticancer drugs and radiation therapy, these limitations have become even more apparent. Fundamentally there are several major approaches to grade tumor response to anticancer treatment if the radiologist wants to move beyond the limitations of a volume- or size-based approach (1). One can study the metabolism of the tumor cells with the help of PET/CT or PET/MRI, analyze restriction of diffusion with MRI, or assess tumor angiogenesis with the help of perfusion CT or MRI.Body perfusion CT also has been declared as a promising and widely available diagnostic tool for staging of oncologic diseases and evaluation of tumor response to chemotherapy and radiation therapy (CRT) (2). But analysis of the literature shows that there are still a limited number of studies proving this statement, and they are based on rather small numbers of patients.New anticancer drugs and radiation therapy methods are targeted exactly to the vascular supply and metabolism of tumors. Monoclonal antibodies and tyrosine kinase inhibitors may dramatically affect tumor-related angiogenesis, preventing the spread of metastasis and improving patient prognosis in responders (3). Accordingly, perfusion CT may be suitable for selecting responders to different types of anticancer treatment and grading the success or failure of the treatment chosen.It is logical to assume that the parameters of tissue perfusion derived from analysis of dynamic CT data sets could serve as specific imaging biomarkers of tumor angiogenesis. The performance of perfusion CT and analysis is not standardized, but the general approach has been established (4). Parameters including blood flow (in mL/100 g/min), blood volume (in mL/100 g), and permeability–surface area product (in mL/100 g/min) are typically used for quantification of perfusion CT data.Most studies of perfusion CT for assessment of tumor response to anticancer therapy reported a decrease of tumor vascularization according to decline in blood flow, blood volume, or permeability–surface area product parameters after CRT. Many publications have demonstrated that antiangiogenic treatment induces a reduction in blood flow and blood volume and permeability values in hepatocellular carcinoma; in renal, colon, and head and neck cancers; and in neuroendocrine tumors (5–9). Usually, the baseline blood flow and blood volume values were higher in responders than in nonresponders to therapy.At first glance, the study by Hamdy et al (10) in this issue of Radiology appears similar to the studies mentioned above with regard to the purpose and methods. The authors selected a rather small group of participants (n = 21) with biopsy-proven pancreatic ductal adenocarcinoma (PDA). This type of cancer has been infrequently studied with perfusion CT. To my knowledge, this is one of the first trials investigating perfusion CT to predict and grade response of PDA to CRT. Authors used a third-generation dual-source scanner to perform low-dose four-dimensional spiral mode perfusion CT of the pancreas during free breathing (40 phases). Pancreatic dynamic perfusion CT was performed before the start of treatment, and in 18 participants, the study was repeated after CRT, before surgery and repeated morphologic assessment. The radiation exposure to study participants was reasonably low (about 13 mSv) because of the use of a current-generation dual-source scanner and optimized scanning protocols.Surprisingly, Hamdy et al obtained results that were different from most of the previous studies of oncologic perfusion CT. In patients with a favorable response to CRT, the parameters of PDA perfusion (first of all, blood flow) were even higher after treatment (median, 54 [interquartile range {IQR}, 42—73] mL/100 g/min) than before CRT (median, 44 [IQR, 39—56] mL/100 g/min ± 12.4) (P = .04). In nonresponders, the increase in tumor blood flow after treatment was not statistically significant. It is also worth noting that the parameters of tissue perfusion in the pancreatic tumors of responders to CRT were higher than those of nonresponders, according to the analysis of baseline perfusion CT performed before the start of CRT. The median baseline blood flow in the responders group was 44 (IQR, 39—56) mL/100 g/min, versus 27 (IQR, 16—52) mL/100 g/min in the nonresponders group (P = .04). In this study, the parameters of initial perfusion CT were in good agreement with the histopathologic response to therapy. There were no significant differences in the grade of tumor response according to the standard Response Evaluation Criteria in Solid Tumors (RECIST) between the responders and nonresponders, and correlation of RECIST grade with histopathologic response was weak. Such well-known biomarkers as serum CA 19-9 was also of no help for grading the results of treatment.These findings do not have a straightforward explanation, but Hamdy et al bring forward some compelling interpretations of these phenomena. The authors suggest that the very dense extracellular matrix typical of PDA is less prominent in responders to CRT. Treatment results in a decrease in the desmoplastic process, freeing the blood vessels from dense extracellular matrix and improving blood flow in the tumor and making it more sensitive to CRT. Also, there is some evidence that in PDA the radiation treatment leads mostly to direct cancer cell death and not to suppression of antiangiogenesis.In general, this small but essential study supports the idea of using perfusion CT for the selection of patients who will benefit most from CRT and for quantification of the tumor response to treatment. Another critical point is that the histologic type of the cancer and a variety of anticancer effects of CRT should be taken into consideration when one interprets the results of perfusion CT.As a pilot study, the study of Hamdy et al had limitations typical for such single-center trials: a small number of participants, short observation time, and heterogeneity of tumor structure (influencing results owing to possible bias related to selections of sites for sampling histologic specimens) and placement of regions of interest for perfusion analysis. But this research shows us a new direction for perfusion CT for patients with cancer and helps us understand the value of perfusion CT for monitoring therapeutic response to CRT.Disclosures of Conflicts of Interest: V.S. disclosed no relevant relationships.References1. Luna A, Vilanova JC, Da Cruz LCH Jr, Rossi SE, eds. Functional Imaging in Oncology: Clinical Applications. Berlin, Germany: Springer, 2014. Google Scholar2. Prezzi D, Khan A, Goh V. Perfusion CT imaging of treatment response in oncology. Eur J Radiol 2015;84(12):2380–2385. Crossref, Medline, Google Scholar3. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005;307(5706):58–62. Crossref, Medline, Google Scholar4. Petralia G, Bonello L, Viotti S, Preda L, d’Andrea G, Bellomi M. CT perfusion in oncology: how to do it. Cancer Imaging 2010;10(1):8–19. Crossref, Medline, Google Scholar5. Fan AC, Sundaram V, Kino A, Schmiedeskamp H, Metzner TJ, Kamaya A. Early Changes in CT Perfusion Parameters: Primary Renal Carcinoma Versus Metastases After Treatment with Targeted Therapy. Cancers (Basel) 2019;11(5):608. Crossref, Google Scholar6. Sahani DV, Holalkere NS, Mueller PR, Zhu AX. Advanced hepatocellular carcinoma: CT perfusion of liver and tumor tissue--initial experience. Radiology 2007;243(3):736–743. Link, Google Scholar7. Dighe S, Castellano E, Blake H, et al. Perfusion CT to assess angiogenesis in colon cancer: technical limitations and practical challenges. Br J Radiol 2012;85(1018):e814–e825. Crossref, Medline, Google Scholar8. Bisdas S, Surlan-Popovic K, Didanovic V, Vogl TJ. Functional CT of squamous cell carcinoma in the head and neck: repeatability of tumor and muscle quantitative measurements, inter- and intra-observer agreement. Eur Radiol 2008;18(10):2241–2250. Crossref, Medline, Google Scholar9. Jiang T, Kambadakone A, Kulkarni NM, Zhu AX, Sahani DV. Monitoring response to antiangiogenic treatment and predicting outcomes in advanced hepatocellular carcinoma using image biomarkers, CT perfusion, tumor density, and tumor size (RECIST). Invest Radiol 2012;47(1):11–17. Crossref, Medline, Google Scholar10. Hamdy A, Ichikawa Y, Toyomasu Y, et al. Perfusion CT to assess response to neoadjuvant chemotherapy and radiation therapy in pancreatic ductal adenocarcinoma: initial experience. Radiology 2019;292:628–635. Link, Google ScholarArticle HistoryReceived: June 5 2019Revision requested: June 16 2019Revision received: June 18 2019Accepted: June 20 2019Published online: July 9 2019Published in print: Sept 2019 FiguresReferencesRelatedDetailsCited ByAdvances in the imaging of gastroenteropancreatic neuroendocrine neoplasmsAnupamaRamachandran, Kumble SeetharamaMadhusudhan2022 | World Journal of Gastroenterology, Vol. 28, No. 26The flow-metabolism ratio might predict treatment response and survival in patients with locally advanced esophageal squamous cell carcinomaKeweiZhao, ChunshengWang, QingfengMao, DongpingShang, YongHuang, LiMa, JinmingYu, MinghuanLi2020 | EJNMMI Research, Vol. 10, No. 1Accompanying This ArticlePerfusion CT to Assess Response to Neoadjuvant Chemotherapy and Radiation Therapy in Pancreatic Ductal Adenocarcinoma: Initial ExperienceJul 9 2019RadiologyRecommended Articles Perfusion CT to Assess Response to Neoadjuvant Chemotherapy and Radiation Therapy in Pancreatic Ductal Adenocarcinoma: Initial ExperienceRadiology2019Volume: 292Issue: 3pp. 628-635Pancreatic Adenocarcinoma Staging in the Era of Preoperative Chemotherapy and Radiation TherapyRadiology2018Volume: 287Issue: 2pp. 374-39018F-FDG PET/CT for the Evaluation of Therapy Response in Hormone Receptor–Positive Bone-Dominant Metastatic Breast CancerRadiology: Imaging Cancer2022Volume: 4Issue: 618F FDG PET/CT and Novel Molecular Imaging for Directing Immunotherapy in CancerRadiology2022Volume: 304Issue: 2pp. 246-264PET of Poly (ADP-Ribose) Polymerase Activity in Cancer: Preclinical Assessment and First In-Human StudiesRadiology2016Volume: 282Issue: 2pp. 453-463See More RSNA Education Exhibits Gluco-CEST (Chemical Exchange Saturation Transfer) Imaging: Principles and ApplicationsDigital Posters2018PET Imaging in Oncology: An Updated Review of Evidence-based IndicationsDigital Posters2020Assessing Immunotherapy with Functional and Molecular Imaging and Radiomics: Whence and WitherDigital Posters2019 RSNA Case Collection Pancreaticoduodenal artery aneurysms with concurrent SMA stenosisRSNA Case Collection2020Metformin related FDG avidity in the bowelRSNA Case Collection2021Malignant pleural mesotheliomaRSNA Case Collection2020 Vol. 292, No. 3 Metrics Altmetric Score PDF download