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Is a single portal venous phase in contrast-enhanced CT sufficient to detect metastases or recurrence in clear cell renal cell carcinoma? – a single-center retrospective study

Is a single portal venous phase in contrast-enhanced CT sufficient to detect metastases or... Background: This study aims at describing the imaging features of the metastatic presentation of clear cell renal cell carcinoma (ccRCC) in arterial (AP) and portal venous phase (PVP) of contrast-enhanced-computed-tomography (CECT) during clinical follow-up (FU) and to evaluate the necessity of a dual phase approach for metastasis detection. Methods: We identified a total of 584 patients that were diagnosed with ccRCC between January 2016 and April 2020. Inclusion criteria were histologically proven ccRCC with metastatic spread, proven by histology or interim follow-up of at least 2 years and follow-up CT examination with AP and PVP CECT including thorax/abdomen and pelvis. Exclusion criteria were defined by missing or incomplete CT-scans or lack of sufficient follow-up. CT studies of 43 patients with histologically proven ccRCCs were analyzed in retrospect. AP and PVP images were analyzed by two radiologists for metastases, two additional independent radiologists analyzed PVP images only. A 5-point Likert scale was used to evaluate the likelihood off the presence of metastasis. Imaging patterns of the metastases were analyzed visually. Results: 43 patients (16 female; mean age: 67±10 years) with recurrent ccRCC and metastatic disease were included. Three imaging patterns were observed (solid, heterogeneous or cystic metastases), which rarely exhibited calcifications (2%). All metastases showed hyperenhancement in AP and PVP. Inter-reader agreement was substantial (Fleiss’ κ 0.6–0.8, p<0.001). No significant differences in sensitivity or specificity between readers (AP and PVP images vs. PVP images only) were present (79.4-85.2%, 97.1-99.6%, p ≥ 0.05). The area under the receiver- operating-characteristic (ROC) curve was between 0.901and 0.922 for all four radiologists. * Correspondence: jens.bedke@med.uni-tuebingen.de Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076 Tübingen, Germany Department of Urology, University Hospital of Tübingen Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076 Tübingen, Germany Full list of author information is available at the end of the article © The Author(s). 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data. Hagen et al. Cancer Imaging (2022) 22:9 Page 2 of 9 Conclusions: Similar rates for detection, sensitivity and specificity of metastasis and local recurrence in ccRCC were observed irrespective of using a dual-phase protocol with AP and PVP or a single PVP protocol only. Thus, a single- phase examination of PVP can be sufficient for experienced radiologists to detect metastatic disease in the follow- up of ccRCC patients. Keywords: Arterial contrast phase, Image quality, Interreader-agreement, Portal venous contrast phase, Renal cell carcinoma Introduction Materials and methods With an incidence of about 115 per 100.000 habitants Data collection and study cohort in Europe renal cell carcinoma (RCC) still leads to a This retrospective data evaluation was approved by the considerable number of deaths each year (49 per institutional review board (approval number 197/ 100.000) [1]. However, with the introduction of new 2020BO2). Verbal and written informed consent were immune checkpoint inhibitors the progression-free waived for this retrospective study. The data were col- survival as well as the overall survival has increased lected from the institution’s electronic medical records. over the last years, leading to a higher rate of follow- We identified a total of 584 patients that were diagnosed up examinations per patient [2]. Besides chromophobe with ccRCC between January 2016 and April 2020. In- and papillary RCCs, clear cell RCC (ccRCC) represent clusion criteria were as follows: (1) Histologically proven the most common histological subtype, differing in ccRCC, (2) metastatic spread of the ccRCC, proven by metastatic predilection sites, among other features [3]. histology or interim follow-up of at least 2 years as evi- Detection and staging of RCCs by cross-sectional im- dence of metastasis, (3) follow-up CT examination with aging achieves a good sensitivity and specificity, both AP and PVP CECT. Exclusion criteria were defined by by computed tomography (CT) and by magnetic res- missing or incomplete CT-scans or an insufficient onance imaging (MRI) [4]. Therefore, an established follow-up as evidence of new metastatic occurrences. and approved staging recommendation regimen is es- This was most frequently due to the contraindication of sential. Guidelines of the European Association of Ur- contrast agent injection such as a creatinine clearance ology (EAU) define criteria for initial diagnosis and below 30mL/min/kg resulting in a change of the follow- staging of renal cell carcinoma by the employment of up protocol (non-enhanced chest CT and abdominal a multi-phasic contrast-enhanced computed tomog- MRI). Of those patients remaining, 43 were included in raphy (CECT) of the abdomen and chest [5]. How- the study (Fig. 1). Of those, 22 patients had no previous ever, imaging protocols for an adequate follow-up treatment, 11 patients had undergone first-line treat- examination are still up for debate [6–9]. ment (6 with checkpoint inhibitor/5 with tyrosine kinase Metastatic lesions of ccRCC occur mainly in the inhibitor) and 10 had undergone second line treatment lungs and bones [10]. While local recurrences, pan- (6 with checkpoint inhibitor/4 with tyrosine kinase creatic or hepatic lesions are less common [10], a de- inhibitor). creased contrast between normal parenchyma and the metastases in parenchymal organs can be detrimential Image acquisition for the detection of metastases in solid organs [11– All CT examinations were performed on a third gener- 13]. Thus, some authors favor the addition of an ar- ation dual-energy scanner consisting of two 192 detector terial phase (AP) to a portal venous phase (PVP) for rows (Siemens SOMATOM Force, Siemens Healthi- staging in the follow-up of ccRCC [11, 12, 14]. This neers, Forchheim, Germany). The CT-images of the is, however, in contrast to ongoing attempts to lower thorax and abdomen/pelvis were acquired in dual- radiation doses and examination time while maintain- energy technique using a tube current of 300mAs ing diagnostic performance. These trade-offs seem to (CARE Dose4D) for tube A (100 kV) and ref. 232mAs be tolerabletosomeextendasnot everysingleme- tube current for tube B (Sn150kV), 0.6 mm single colli- tastasis necessarily leads to a change in the thera- mation width, spiral pitch factor 0.6, matrix 512 × 512 peutic regimen [12]. and a convolution kernel Br40 for arterial and Bf40 for Therefore, the aim of this study was to evaluate the PVP image data sets (see Table 1). Image reconstruction impact of a two-phase contrast-enhanced CT of the ab- was performed with a thickness of 3 mm in 2 planes domen and chest in patients with metastatic ccRCC in (axial and coronary) for both contrast phases. Further- comparison to a single, portal venous phase CT, regard- more, high-resolution reconstructions and maximum in- ing the diagnostic accuracy for the detection of recurrent tensity projections from the PV image datasets were tumors or metastases. included in the analysis. All patients received Hagen et al. Cancer Imaging (2022) 22:9 Page 3 of 9 Fig. 1 Study population Iomeprol as contrast agent (Imerone 400; Bracco, weight in g+20 =amountofcontrastagent in mL.) Milan, Italy) intravenously by a dual syringe injector following the subsequent flow and delay depending at 2-3 mL/sec (CT Stellant, Medrad, Indianola, PA, on the contrast phase (see Table 1): Based on the USA) followed by a saline chaser bolus. To improve findings of Itoh et al., reporting similar detection both image quality and parenchymal enhancement the rates for the late arterial contrast phase after 24.6 to contrast agent was applied taking into account a lean 36.0 Sect. [16]. Theportalvenousphase wasset body weight-adapted dosing protocol [15] (body based on the findings of Birnbaum et al., reporting nephrographic phase after 60 to 136 Sect. [17]. Table 1 Image acquisition parameters and contrast medium Arterial Phase Portal Venous Phase Assessment of imaging features on CT Single collimation width 0.6 0.6 Four radiologists with 2, 4, 8 and 12 years of experience in reading oncological CT images analyzed the data sets Spiral pitch factor 0.6 0.6 in two groups and were blinded to the number and loca- Tube voltages (keV) 120 100 and 150 tion of the metastases: The first group consisted of the Ref. tube current (mAs)* 275 300 and 232 less experienced radiologists (2 and 4 years of experi- Matrix 512 × 512 512 × 512 ence) and read both data sets, the AP and the PVP. The Reconstruction kernel Br40 Bf40 second group of radiologists (8 and 12 years of experi- Delay between contrast 35 s p.i. 65 s p.i. ence) only had the PVP data sets available for the identi- agent injection and scan fication of metastases. As ground truth for the presence Flow 2-3 mL/sec 2-3 mL/sec of metastatic lesions every patient had a follow-up *Care Dose4D, p.i.: post injection within a timespan of at least 2 years with interval growth Hagen et al. Cancer Imaging (2022) 22:9 Page 4 of 9 or the metastasis were resected and proven by histology. osteolytic with a soft tissue component (n = 18, 41.9%). Suspicious lesions were defined as hypervascularized le- Metastases were found less frequently in the pancreas (n sions with distortion of the normal organ structure. Ten = 7, 16.3%, example given in Fig. 2), soft tissues (n =8, potential manifestation regions were defined before 18.6%) and the contralateral kidney (n = 9, 20.9%). reading: either local recurrences, or systemic recur- Twenty-one patients received a therapy with an rences, such as manifestation at the opposite kidney, immune-checkpoint-inhibitor, a tyrosine-kinase-inhibitor peritoneal metastases, lymph node metastases, pancre- at follow-up examination (Table 2). Of those, 10 patients atic metastases, hepatic metastases, adrenal metastases, presented with a second line therapy (e.g. Nivolumab) due pulmonary metastases, soft-tissue metastases and bone to their initial synchronously metastatic ccRCC. metastases. All lesions were scored individually on the No significant difference in sensitivity, specificity and 5-point Likert scale (1 = no metastasis, 2 = unlikely me- accuracy between group 1 (Radiologist #1 and #2, read- tastasis, 3 = possible metastasis, 4 = most likely metasta- ing AP and PVP) and group 2 (Radiologist #3 and #4 sis, 5 = definite metastasis). Only lesions classified as reading PVP only) could be found (p ≥ 0.05, Table 3). “most likely” or “definite” (Likert 4 and 5) were consid- Overall, a sensitivity of 82.3% for the first and 83.1% for ered as positive metastasis. Furthermore, the lesions the second group was achieved. The area under the re- were classified depending on their visual aspect and the ceiver operating characteristic (ROC) curve ranged be- measured Hounsfield units as being solid, cystic hetero- tween 0.901 and 0.922 (CI: 0.884 – 0.959, Table 4; geneous. The presence or absence of calcification was Fig. 3). also determined. Overall, the four radiologists had a good to very good inter-reader agreement (κ ranging from 0.6 to 0.83, p< Statistics 0.001). Pulmonary metastases were associated with the Statistical analysis was performed using SPSS (version worst inter-reader agreement whereas peritoneal metas- 27.0.0, IBM, Armonk, NY, USA). Continuous data were tases coincided with the best inter-reader agreement. Le- expressed as means ± standard deviation (SD). Differ- sions in parenchymatous organs as for example ences in the number of imaging patterns (solid, cystic, pancreatic lesions (Fig. 2) or local recurrences (Fig. 4) heterogenous) were tested by the Kruskal–Wallis H test. achieved an average interrater agreement. No significant Interrater reliability between the 4 readers was tested difference (p ≥ 0.05) in total lesion detection could be with Fleiss’ Kappa (κ). Values from 0.0 to 0.2 indicate registered between the four radiologists (118 to 136 of slight agreement, 0.21 to 0.40 fair agreement, 0.41 to 155 possible lesions detected, Table 5). 0.60 moderate agreement, 0.61 to 0.80 substantial agree- ment, and values ranging from 0.81 to 1.0 indicate al- Discussion most perfect or perfect agreement [18]. Sensitivity, This study shows that the detection of metastatic lesions specificity as well as accuracy were calculated for every of ccRCC can be performed with excellent comparable radiologist and plotted on a receiver operating character- sensitivity and specificity between single PVP imaging istics (ROC)-curve. Determination of the optimal cut-off and dual, AP and PVP, imaging. point was achieved by the Youden index. After verifica- Both groups achieved a good sensitivity of 82.3% for tion of the non-Gaussian distribution of every parameter the AP + PVP group and 83.1% for the PVP only group, by the Shapiro-Wilk test, we opted for a non-parametric whereas the specificity of both groups was excellent with test (Kruskal-Wallis-H test) to analyze differences be- 98.4% and 99.5%, respectively. This resulted in a good to tween the four independent radiologists. A two-tailed p- very good interrater agreement for the ten potential value of less than 0.05 was considered to indicate statis- metastatic sides evaluated in this study. Moreover, all tical significance. four readers achieved a very good area under the ROC curves (>0.9, Table 4). Results In our cohort, 7 of the 43 patients had pancreatic me- The mean patient age at the time point of CT examin- tastases. Of these, every single radiologist detected 6 ation was 67 ± 10 years. The 27 male and 16 female pa- (86%) pancreatic lesions as such. Recent publications tients presented with a total of 155 metastatic lesions claimed that especially metastatic lesions of the pancreas (mean 3.6 metastatic lesions per patient). The majority are more easily detectable in the arterial contrast phase of lesions were solid lesions (102/155) followed by het- [11, 13]. This might be due to the early arterial enhance- erogeneous (43/155) and cystic lesions (10/155) (p= ment of pancreatic metastasis compared to parenchyma 0.001). Only 2% of the lesions presented with calcifica- [19]. Particularly, initial small sized pancreatic metasta- tions. Most of the metastatic lesions were found in the ses, which often occur metachronous several years after lungs (n = 31, 72.1%) followed by lymph node metasta- the initial diagnosis, might increase true-positive lesion ses (n = 30, 69.8%) and bone metastases, appearing detection [20]. In fact, even the radiologists who read Hagen et al. Cancer Imaging (2022) 22:9 Page 5 of 9 Fig. 2 Axial CT images of the pancreas in arterial (A) and portal venous (B) phases of a 65-year-old woman with metastatic RCC. In both phases the metastasis is visible as a hypervascularized lesion (white arrows) the PVP datasets only achieved a higher detection rate Furthermore, good interrater agreement between the than in recently published literature (86% vs. 50 – 69%) use of PVP only and the combination of PVP and AP [11]. A reason for this might be the earlier imaging time was achieved for the upper abdominal organs, especially point in our study protocol compared to Corwin et al. for detection of hepatic and renal metastases. Our re- (65 s vs. 80-90 s) [11]. In contrast to Jain et al., who re- sults reinforce the assumption that an additional AP in ported a visualization of pancreatic metastases in the the detection of ccRCC metastasis might be of limited PVP or AP datasets only of up to 25% [12], we perceived value that has been controversially discussed in the lit- all pancreatic metastases equally in both phases. Further- erature for liver metastases [12, 22]. Advances in DECT more, 4 of the 7 pancreatic metastases occurred in pa- with an improved assessment of hypodense liver lesions tients receiving no therapy. Especially targeted-therapy in the PVP by switching keV levels in monoenergetic re- results in reduced density of parenchymatous organs in constructions [23] might confirm this notion in the fu- the arterial phase of CECT [21]. These might be reasons ture. Some authors state the necessity of an AP for the for the contrast between pancreatic parenchyma and detection of renal metastases, especially for local recur- pancreatic metastasis (see Fig. 2). rence [14]. For our cohort, we cannot confirm this hy- pothesis as we found that local recurrences were Table 2 Patient characteristics detected at comparable rates in the PVP only (10 lesions Total detected in the AP+PVP group vs. 9 lesions detected for PVP only group, Table 5). Griffin et al. reported that Age [mean ± standard deviation] 67 ± 10 years local recurrences can be shown on CECT as solid en- Sex [n] 27 male and 16 female hancing masses [14]. As the contrast is higher in hyper- No treatment [n] 22 (51.2%) vascularized lesions in the AP compared to the PVP Treatment with Checkpoint inhibitor 12 (27.9%) [12], Raptopoulos et al. proposed a practical approach by (Nivolumab, Pembrolizumab+ Axitinib) [n] Treatment with tyrosine kinase inhibitor 9 (20.9%) Table 3 Sensitivity, specificity and accuracy of the 4 different (Sorafenib, Cabozantinib, Pazopanib, radiologists depending on the image data sets Sunitinib) [n] Radiologist #1 Accuracy 92.8% Metastatic lesions divided by organ 155 AP + PVP systems (total) [n] Sensitivity 85.2% Pulmonary [n] 31 (20.0%) Specificity 97.1% Lymphatic [n] 30 (19.4%) Radiologist #2 AP + PVP Accuracy 94.9% Osseous [n] 18 (11.6%) Sensitivity 79.4% Hepatic [n] 16 (10.3%) Specificity 99.6% Adrenal [n] 13 (8.4%) Radiologist #3 PVP Accuracy 93.7% Peritoneal [n] 12 (7.7%) Sensitivity 83.2% Local [n] 11 (7.1%) Specificity 99.6% Contralateral kidney [n] 9 (5.8%) Radiologist #4 PVP Accuracy 93.5% Soft tissue [n] 8 (5.2%) Sensitivity 83.1% Pancreatic [n] 7 (4.5%) Specificity 99.3% Hagen et al. Cancer Imaging (2022) 22:9 Page 6 of 9 Table 4 Area under the ROC-Curve Radiologist #1 (AP+PVP) Radiologist #2 Radiologist #3 Radiologist #4 (AP+PVP) (PVP only) (PVP only) AUC 0.918 0.901 0.922 0.913 (CI: 0.884 – 0.952) (CI: 0.863 – 0.939) (CI: 0.889 – 0.956) (CI: 0.878 – 0.949) CI: confidence interval considering an AP und PVP for initial evaluations of pa- lead to additional information for the characterization of tients with metastatic RCCs and the use of the PVP only small nodules. for follow-up examinations [24]. In our study cohort, the missed lesions would not have Pulmonary lesions are the most common site of recur- led to treatment changes as there were more than 3 rence in ccRCC [10, 13], which is in line with 72.1% of metastatic lesions present per patient. This is in line lung metastases in our cohort. Incidental pulmonary with findings reported by Jain et al. where only 2% of nodules are commonly seen on CT-scans of the chest the metastatic lesions lead to a different treatment [12]. and therefore the diagnosis of ccRCC metastasis might However, this might be of importance when only a lim- be difficult without previous examinations [25]. With ited number of metastases are present as the patients only one examination in our study, interrater agreement with oligometastatic disease are prone to metastasect- between the 4 radiologists was still decent (κ 0.6, omy instead of systemic treatment. There were no sig- Table 4). As reported by Price et al., pulmonary metasta- nificant differences when comparing the specificity ses most often appear as solid nodules and masses, between the two groups in our study (98.4% vs. 99.6%). sometimes surrounded by a peripheral ground-glass halo Three typical patterns of the metastases could be dif- [26]. However, adding more contrast phases would not ferentiated: solid, heterogeneous and cystic. As reported Fig. 3 Receiver operating characteristic (ROC) curves depending on the image protocol Hagen et al. Cancer Imaging (2022) 22:9 Page 7 of 9 Fig. 4 Coronal CT images of the local recurrence in arterial (A) and portal venous (B) phases of a 64-year-old man with multiple metastatic RCC by Smith et al., targeted therapies result in distinct pat- Limitations terns of metastatic ccRCCs as they might change their ap- This single-center study is limited by its nonrandomized pearance and enhancement pattern from an initially and retrospective design. Moreover, the lack of histo- homogeneous and non-enhancing mass [27]. This is even logical confirmation of metastases had to be compen- more important as contemporaneous reduction in tumor sated by successional CT-scans permitting the size and attenuation were correlated with favorable clinical evaluation of tissue dynamics. Another confounder may outcomes [28]. However, while no different imaging re- be the fact, that about half of the patients were currently sponse criteria are defined for assessing therapy response receiving therapy, which is likely to cause altered perfu- diameter-based criteria remain essential [29]. sion characteristics of the metastases [12]. As a result of We conclude that staging of metastatic ccRCCs using the low number of cases included, the data may have PVP only resulted in comparable results to dual-phase overestimated the potential of the portal venous contrast CECT and help to reduce radiation exposure. Taking enhanced phase for the detection of metastases. Further- the number of repetitive staging examinations into ac- more, the two “less experienced” radiologists had both count the radiation exposure can be substantially re- phases whereas the two experienced radiologists only duced, although the 5-year overall survival in metastatic had the PV phase, resulting in a certain degree of inter- ccRCC patients is limited [30, 31]. reader bias. However, by getting comparable detection Table 5 Inter-reader agreement depending on metastatic lesions Radiologist #1 Radiologist #2 Radiologist #3 Radiologist #4 Fleiss‘ p-value Kappa κ Pulmonary metastases [n] 31 24 27 27 0.60 ± 0.05 <0.001 Lymph node metastases [n] 26 20 24 23 0.61 ± 0.05 <0.001 Osseous metastases [n] 16 16 17 16 0.76 ± 0.05 <0.001 Hepatic metastases [n] 13 14 15 15 0.66 ± 0.05 <0.001 Adrenal metastases [n] 12 8 6 7 0.63 ± 0.05 <0.001 Peritoneal metastases [n] 9 8 8 8 0.83 ± 0.06 <0.001 Local recurrences [n] 10 10 9 9 0.69 ± 0.05 <0.001 Contralateral kidney [n] 6 6 5 5 0.76 ± 0.04 <0.001 Soft tissue metastases [n] 7 6 8 7 0.69 ± 0.05 <0.001 Pancreatic metastases [n] 6 6 6 6 0.66 ± 0.05 <0.001 Hagen et al. Cancer Imaging (2022) 22:9 Page 8 of 9 rates in both groups the experience seems to replace an Received: 16 June 2021 Accepted: 1 January 2022 additional AP. References Conclusions 1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J In this study, we demonstrate similar rates for detection, Cancer. 2013;49(6):1374–403. https://doi.org/10.1016/j.ejca.2012.12.027. sensitivity and specificity of metastases and local recur- 2. Bedke J, Albiges L, Capitanio U, et al. Updated European Association of rence of ccRCC when comparing a dual phase protocol Urology Guidelines on Renal Cell Carcinoma: Nivolumab plus Cabozantinib Joins Immune Checkpoint Inhibition Combination Therapies for Treatment- with arterial and portal-venous contrast to a single- naïve Metastatic Clear-Cell Renal Cell Carcinoma. Eur Urol. 2020. https://doi. phase protocol with portal-venous contrast. Considering org/10.1016/j.eururo.2020.12.005. a certain experience level, we conclude that a single- 3. Hoffmann NE, Gillett MD, Cheville JC, Lohse CM, Leibovich BC, Blute ML. Differences in organ system of distant metastasis by renal cell carcinoma phase examination might be sufficient for follow-up ex- subtype. J Urol. 2008;179(2):474–7. https://doi.org/10.1016/j.juro.2007.09.036. aminations in patients with metastatic ccRCC. 4. Vogel C, Ziegelmüller B, Ljungberg B, et al. Imaging in Suspected Renal-Cell Carcinoma: Systematic Review. Clin Genitourin Cancer. 2019;17(2):e345–55. https://doi.org/10.1016/j.clgc.2018.07.024. Abbreviations 5. Ljungberg B, Albiges L, Abu-Ghanem Y, et al. European Association of AP: Arterial phase; ccRCC: Clear cell renal cell carcinoma; CECT: Contrast- Urology Guidelines on Renal Cell Carcinoma: The 2019 Update. Eur Urol. enhanced computed tomography; CT: Computed tomography; 2019;75(5):799–810. doi:https://doi.org/10.1016/j.eururo.2019.02.011. EAU: European Association of Urology; FU: Follow-up; MRI: Magnetic 6. Liaw CW, Winoker JS, Mehrazin R. Imaging Protocols for Active Surveillance resonance imaging; PVP: Portal venous phase; RCC: Renal cell carcinoma; in Renal Cell Carcinoma. Curr Urol Rep. 2018;19(10):81. https://doi.org/10.1 ROC: Receiver operating characteristics; SD: Standard deviation 007/s11934-018-0830-z. 7. Chu JS, Wang ZJ. Protocol Optimization for Renal Mass Detection and Acknowledgements Characterization. Radiol Clin North Am. 2020;58(5):851–73. https://doi.org/1 ‘Not applicable’. 0.1016/j.rcl.2020.05.003. 8. Ali O, Fishman EK, Kawamoto S. Recurrent renal cell carcinoma following nephrectomy and ablation therapy: Radiology perspective. Eur J Radiol. Authors’ contributions 2018;107:134–42. https://doi.org/10.1016/j.ejrad.2018.05.002. FH, WT, FP, SKau analyzed and interpreted the patient data regarding the 9. Dabestani S, Marconi L, Kuusk T, Bex A. Follow-up after curative treatment metastases of the RCC. FH and WT had both a major contribution in writing of localised renal cell carcinoma. World J Urol. 2018;36(12):1953–9. https:// the manuscript. JS, AM, AS, KN, SKru and SKau revised the manuscript. All doi.org/10.1007/s00345-018-2338-z. authors read and approved the final manuscript. 10. Chae EJ, Kim JK, Kim SH, Bae S-J, Cho K-S. Renal cell carcinoma: Analysis of postoperative recurrence patterns. Radiology. 2005;234(1):189–96. https:// Funding doi.org/10.1148/radiol.2341031733. ‘Not applicable’. Open Access funding enabled and organized by Projekt 11. Corwin MT, Lamba R, Wilson M, McGahan JP. Renal cell carcinoma DEAL. We acknowledge support by Open Access Publishing Fund of metastases to the pancreas: Value of arterial phase imaging at MDCT. Acta University of Tübingen. Radiol. 2013;54(3):349–54. https://doi.org/10.1258/ar.2012.120693. 12. Jain Y, Liew S, Taylor MB, Bonington SC. Is dual-phase abdominal CT necessary for the optimal detection of metastases from renal cell Availability of data and materials carcinoma? Clin Radiol. 2011;66(11):1055–9. https://doi.org/10.1016/j.crad.2 All data generated or analysed during this study are included in this 011.06.002. published article. 13. Coquia SF, Johnson PT, Ahmed S, Fishman EK. MDCT imaging following nephrectomy for renal cell carcinoma: Protocol optimization and patterns of Declarations tumor recurrence. World J Radiol. 2013;5(11):436–45. https://doi.org/10.4329/ wjr.v5.i11.436. Ethics approval and consent to participate 14. Griffin N, Gore ME, Sohaib SA. Imaging in metastatic renal cell carcinoma. This retrospective data evaluation was approved by the institutional review AJR Am J Roentgenol. 2007;189(2):360–70. https://doi.org/10.2214/AJR.07.2 board which was assigned the approval number 197/2020BO2. Verbal and written informed consent were waived due to the retrospective nature of 15. Caruso D, Rosati E, Panvini N, et al. Optimization of contrast medium the study. Consent for publication was given by all authors. volume for abdominal CT in oncologic patients: prospective comparison between fixed and lean body weight-adapted dosing protocols. Insights Imaging. 2021;12(1):40. https://doi.org/10.1186/s13244-021-00980-0. Consent for publication 16. Itoh S, Ikeda M, Achiwa M, Satake H, Iwano S, Ishigaki T. Late-arterial and ‘Not applicable’. portal-venous phase imaging of the liver with a multislice CT scanner in patients without circulatory disturbances: automatic bolus tracking or Competing interests empirical scan delay? Eur Radiol. 2004;14(9):1665–73. https://doi.org/10.1 ‘Not applicable’. 007/s00330-004-2321-5. 17. Birnbaum BA, Jacobs JE, Langlotz CP, Ramchandani P. Assessment of a Author details bolus-tracking technique in helical renal CT to optimize nephrographic Department of Diagnostic and Interventional Radiology, phase imaging. Radiology. 1999;211(1):87–94. https://doi.org/10.1148/ra Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076 Tübingen, Germany. diology.211.1.r99ap4187. Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076 18. Landis JR, Koch GG. The measurement of observer agreement for Tübingen, Germany. Clinic of Urology, Siloah St. Trudpert Klinikum, categorical data. Biometrics. 1977;33(1):159–74. Wilferdinger Str. 67, 75179 Pforzheim, Germany. Department of Urology, 19. Tordjman M, Dbjay J, Chamouni A, et al. Clear Cell Papillary Renal Cell University Hospital of Tübingen Eberhard-Karls-University, Hoppe-Seyler-Str.3, Carcinoma: A Recent Entity With Distinct Imaging Patterns. AJR Am J 72076 Tübingen, Germany. Diagnostic and Interventional Radiology, Siloah Roentgenol. 2020;214(3):579–87. https://doi.org/10.2214/AJR.19.21681. St. Trudpert Klinikum, Wilferdinger Str. 67, 75179 Pforzheim, Germany. 20. Mechó S, Quiroga S, Cuéllar H, Sebastià C. Pancreatic metastasis of renal cell Department of Nuclear Medicine, University Hospital Ulm, carcinoma: Multidetector CT findings. Abdom Imaging. 2009;34(3):385–9. Albert-Einstein-Allee 23, 89081 Ulm, Germany. https://doi.org/10.1007/s00261-008-9391-9. Hagen et al. Cancer Imaging (2022) 22:9 Page 9 of 9 21. Nathan PD, Vinayan A, Stott D, Juttla J, Goh V. CT response assessment combining reduction in both size and arterial phase density correlates with time to progression in metastatic renal cancer patients treated with targeted therapies. Cancer Biol Ther. 2010;9(1):15–9. https://doi.org/10.4161/ cbt.9.1.10340. 22. Francis IR, Cohan RH, McNulty NJ, et al. Multidetector CT of the liver and hepatic neoplasms: Effect of multiphasic imaging on tumor conspicuity and vascular enhancement. AJR Am J Roentgenol. 2003;180(5):1217–24. https:// doi.org/10.2214/ajr.180.5.1801217. 23. Caruso D, Cecco CN de, Schoepf UJ, et al. Can dual-energy computed tomography improve visualization of hypoenhancing liver lesions in portal venous phase? Assessment of advanced image-based virtual monoenergetic images. Clin Imaging. 2017;41:118–24. https://doi.org/10.101 6/j.clinimag.2016.10.015. 24. Raptopoulos VD, Blake SP, Weisinger K, Atkins MB, Keogan MT, Kruskal JB. Multiphase contrast-enhanced helical CT of liver metastases from renal cell carcinoma. Eur Radiol. 2001;11(12):2504–9. https://doi.org/10.1007/s0033001 25. Blagev DP, Lloyd JF, Conner K, et al. Follow-up of incidental pulmonary nodules and the radiology report. J Am Coll Radiol. 2014;11(4):378–83. https://doi.org/10.1016/j.jacr.2013.08.003. 26. Price M, Wu CC, Genshaft S, et al. Imaging and Management of Intrathoracic Renal Cell Carcinoma Metastases. AJR Am J Roentgenol. 2018; 210(6):1181–91. https://doi.org/10.2214/AJR.18.19645. 27. Smith AD, Lieber ML, Shah SN. Assessing tumor response and detecting recurrence in metastatic renal cell carcinoma on targeted therapy: Importance of size and attenuation on contrast-enhanced CT. AJR Am J Roentgenol. 2010;194(1):157–65. https://doi.org/10.2214/AJR.09.2941. 28. Thian Y, Gutzeit A, Koh D-M, et al. Revised Choi imaging criteria correlate with clinical outcomes in patients with metastatic renal cell carcinoma treated with sunitinib. Radiology. 2014;273(2):452–61. https://doi.org/10.114 8/radiol.14132702. 29. Schwartz LH, Litière S, Vries E de, et al. RECIST 1.1-Update and clarification: From the RECIST committee. Eur J Cancer. 2016;62:132–7. https://doi.org/1 0.1016/j.ejca.2016.03.081. 30. Rini BI, Powles T, Atkins MB, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. The Lancet. 2019;393(10189):2404–15. https://doi.org/10.101 6/S0140-6736(19)30723-8. 31. Méjean A, Ravaud A, Thezenas S, et al. Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma. N Engl J Med. 2018;379(5): 417–27. https://doi.org/10.1056/NEJMoa1803675. Publisher’sNote Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Imaging Springer Journals

Is a single portal venous phase in contrast-enhanced CT sufficient to detect metastases or recurrence in clear cell renal cell carcinoma? – a single-center retrospective study

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Abstract

Background: This study aims at describing the imaging features of the metastatic presentation of clear cell renal cell carcinoma (ccRCC) in arterial (AP) and portal venous phase (PVP) of contrast-enhanced-computed-tomography (CECT) during clinical follow-up (FU) and to evaluate the necessity of a dual phase approach for metastasis detection. Methods: We identified a total of 584 patients that were diagnosed with ccRCC between January 2016 and April 2020. Inclusion criteria were histologically proven ccRCC with metastatic spread, proven by histology or interim follow-up of at least 2 years and follow-up CT examination with AP and PVP CECT including thorax/abdomen and pelvis. Exclusion criteria were defined by missing or incomplete CT-scans or lack of sufficient follow-up. CT studies of 43 patients with histologically proven ccRCCs were analyzed in retrospect. AP and PVP images were analyzed by two radiologists for metastases, two additional independent radiologists analyzed PVP images only. A 5-point Likert scale was used to evaluate the likelihood off the presence of metastasis. Imaging patterns of the metastases were analyzed visually. Results: 43 patients (16 female; mean age: 67±10 years) with recurrent ccRCC and metastatic disease were included. Three imaging patterns were observed (solid, heterogeneous or cystic metastases), which rarely exhibited calcifications (2%). All metastases showed hyperenhancement in AP and PVP. Inter-reader agreement was substantial (Fleiss’ κ 0.6–0.8, p<0.001). No significant differences in sensitivity or specificity between readers (AP and PVP images vs. PVP images only) were present (79.4-85.2%, 97.1-99.6%, p ≥ 0.05). The area under the receiver- operating-characteristic (ROC) curve was between 0.901and 0.922 for all four radiologists. * Correspondence: jens.bedke@med.uni-tuebingen.de Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076 Tübingen, Germany Department of Urology, University Hospital of Tübingen Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076 Tübingen, Germany Full list of author information is available at the end of the article © The Author(s). 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data. Hagen et al. Cancer Imaging (2022) 22:9 Page 2 of 9 Conclusions: Similar rates for detection, sensitivity and specificity of metastasis and local recurrence in ccRCC were observed irrespective of using a dual-phase protocol with AP and PVP or a single PVP protocol only. Thus, a single- phase examination of PVP can be sufficient for experienced radiologists to detect metastatic disease in the follow- up of ccRCC patients. Keywords: Arterial contrast phase, Image quality, Interreader-agreement, Portal venous contrast phase, Renal cell carcinoma Introduction Materials and methods With an incidence of about 115 per 100.000 habitants Data collection and study cohort in Europe renal cell carcinoma (RCC) still leads to a This retrospective data evaluation was approved by the considerable number of deaths each year (49 per institutional review board (approval number 197/ 100.000) [1]. However, with the introduction of new 2020BO2). Verbal and written informed consent were immune checkpoint inhibitors the progression-free waived for this retrospective study. The data were col- survival as well as the overall survival has increased lected from the institution’s electronic medical records. over the last years, leading to a higher rate of follow- We identified a total of 584 patients that were diagnosed up examinations per patient [2]. Besides chromophobe with ccRCC between January 2016 and April 2020. In- and papillary RCCs, clear cell RCC (ccRCC) represent clusion criteria were as follows: (1) Histologically proven the most common histological subtype, differing in ccRCC, (2) metastatic spread of the ccRCC, proven by metastatic predilection sites, among other features [3]. histology or interim follow-up of at least 2 years as evi- Detection and staging of RCCs by cross-sectional im- dence of metastasis, (3) follow-up CT examination with aging achieves a good sensitivity and specificity, both AP and PVP CECT. Exclusion criteria were defined by by computed tomography (CT) and by magnetic res- missing or incomplete CT-scans or an insufficient onance imaging (MRI) [4]. Therefore, an established follow-up as evidence of new metastatic occurrences. and approved staging recommendation regimen is es- This was most frequently due to the contraindication of sential. Guidelines of the European Association of Ur- contrast agent injection such as a creatinine clearance ology (EAU) define criteria for initial diagnosis and below 30mL/min/kg resulting in a change of the follow- staging of renal cell carcinoma by the employment of up protocol (non-enhanced chest CT and abdominal a multi-phasic contrast-enhanced computed tomog- MRI). Of those patients remaining, 43 were included in raphy (CECT) of the abdomen and chest [5]. How- the study (Fig. 1). Of those, 22 patients had no previous ever, imaging protocols for an adequate follow-up treatment, 11 patients had undergone first-line treat- examination are still up for debate [6–9]. ment (6 with checkpoint inhibitor/5 with tyrosine kinase Metastatic lesions of ccRCC occur mainly in the inhibitor) and 10 had undergone second line treatment lungs and bones [10]. While local recurrences, pan- (6 with checkpoint inhibitor/4 with tyrosine kinase creatic or hepatic lesions are less common [10], a de- inhibitor). creased contrast between normal parenchyma and the metastases in parenchymal organs can be detrimential Image acquisition for the detection of metastases in solid organs [11– All CT examinations were performed on a third gener- 13]. Thus, some authors favor the addition of an ar- ation dual-energy scanner consisting of two 192 detector terial phase (AP) to a portal venous phase (PVP) for rows (Siemens SOMATOM Force, Siemens Healthi- staging in the follow-up of ccRCC [11, 12, 14]. This neers, Forchheim, Germany). The CT-images of the is, however, in contrast to ongoing attempts to lower thorax and abdomen/pelvis were acquired in dual- radiation doses and examination time while maintain- energy technique using a tube current of 300mAs ing diagnostic performance. These trade-offs seem to (CARE Dose4D) for tube A (100 kV) and ref. 232mAs be tolerabletosomeextendasnot everysingleme- tube current for tube B (Sn150kV), 0.6 mm single colli- tastasis necessarily leads to a change in the thera- mation width, spiral pitch factor 0.6, matrix 512 × 512 peutic regimen [12]. and a convolution kernel Br40 for arterial and Bf40 for Therefore, the aim of this study was to evaluate the PVP image data sets (see Table 1). Image reconstruction impact of a two-phase contrast-enhanced CT of the ab- was performed with a thickness of 3 mm in 2 planes domen and chest in patients with metastatic ccRCC in (axial and coronary) for both contrast phases. Further- comparison to a single, portal venous phase CT, regard- more, high-resolution reconstructions and maximum in- ing the diagnostic accuracy for the detection of recurrent tensity projections from the PV image datasets were tumors or metastases. included in the analysis. All patients received Hagen et al. Cancer Imaging (2022) 22:9 Page 3 of 9 Fig. 1 Study population Iomeprol as contrast agent (Imerone 400; Bracco, weight in g+20 =amountofcontrastagent in mL.) Milan, Italy) intravenously by a dual syringe injector following the subsequent flow and delay depending at 2-3 mL/sec (CT Stellant, Medrad, Indianola, PA, on the contrast phase (see Table 1): Based on the USA) followed by a saline chaser bolus. To improve findings of Itoh et al., reporting similar detection both image quality and parenchymal enhancement the rates for the late arterial contrast phase after 24.6 to contrast agent was applied taking into account a lean 36.0 Sect. [16]. Theportalvenousphase wasset body weight-adapted dosing protocol [15] (body based on the findings of Birnbaum et al., reporting nephrographic phase after 60 to 136 Sect. [17]. Table 1 Image acquisition parameters and contrast medium Arterial Phase Portal Venous Phase Assessment of imaging features on CT Single collimation width 0.6 0.6 Four radiologists with 2, 4, 8 and 12 years of experience in reading oncological CT images analyzed the data sets Spiral pitch factor 0.6 0.6 in two groups and were blinded to the number and loca- Tube voltages (keV) 120 100 and 150 tion of the metastases: The first group consisted of the Ref. tube current (mAs)* 275 300 and 232 less experienced radiologists (2 and 4 years of experi- Matrix 512 × 512 512 × 512 ence) and read both data sets, the AP and the PVP. The Reconstruction kernel Br40 Bf40 second group of radiologists (8 and 12 years of experi- Delay between contrast 35 s p.i. 65 s p.i. ence) only had the PVP data sets available for the identi- agent injection and scan fication of metastases. As ground truth for the presence Flow 2-3 mL/sec 2-3 mL/sec of metastatic lesions every patient had a follow-up *Care Dose4D, p.i.: post injection within a timespan of at least 2 years with interval growth Hagen et al. Cancer Imaging (2022) 22:9 Page 4 of 9 or the metastasis were resected and proven by histology. osteolytic with a soft tissue component (n = 18, 41.9%). Suspicious lesions were defined as hypervascularized le- Metastases were found less frequently in the pancreas (n sions with distortion of the normal organ structure. Ten = 7, 16.3%, example given in Fig. 2), soft tissues (n =8, potential manifestation regions were defined before 18.6%) and the contralateral kidney (n = 9, 20.9%). reading: either local recurrences, or systemic recur- Twenty-one patients received a therapy with an rences, such as manifestation at the opposite kidney, immune-checkpoint-inhibitor, a tyrosine-kinase-inhibitor peritoneal metastases, lymph node metastases, pancre- at follow-up examination (Table 2). Of those, 10 patients atic metastases, hepatic metastases, adrenal metastases, presented with a second line therapy (e.g. Nivolumab) due pulmonary metastases, soft-tissue metastases and bone to their initial synchronously metastatic ccRCC. metastases. All lesions were scored individually on the No significant difference in sensitivity, specificity and 5-point Likert scale (1 = no metastasis, 2 = unlikely me- accuracy between group 1 (Radiologist #1 and #2, read- tastasis, 3 = possible metastasis, 4 = most likely metasta- ing AP and PVP) and group 2 (Radiologist #3 and #4 sis, 5 = definite metastasis). Only lesions classified as reading PVP only) could be found (p ≥ 0.05, Table 3). “most likely” or “definite” (Likert 4 and 5) were consid- Overall, a sensitivity of 82.3% for the first and 83.1% for ered as positive metastasis. Furthermore, the lesions the second group was achieved. The area under the re- were classified depending on their visual aspect and the ceiver operating characteristic (ROC) curve ranged be- measured Hounsfield units as being solid, cystic hetero- tween 0.901 and 0.922 (CI: 0.884 – 0.959, Table 4; geneous. The presence or absence of calcification was Fig. 3). also determined. Overall, the four radiologists had a good to very good inter-reader agreement (κ ranging from 0.6 to 0.83, p< Statistics 0.001). Pulmonary metastases were associated with the Statistical analysis was performed using SPSS (version worst inter-reader agreement whereas peritoneal metas- 27.0.0, IBM, Armonk, NY, USA). Continuous data were tases coincided with the best inter-reader agreement. Le- expressed as means ± standard deviation (SD). Differ- sions in parenchymatous organs as for example ences in the number of imaging patterns (solid, cystic, pancreatic lesions (Fig. 2) or local recurrences (Fig. 4) heterogenous) were tested by the Kruskal–Wallis H test. achieved an average interrater agreement. No significant Interrater reliability between the 4 readers was tested difference (p ≥ 0.05) in total lesion detection could be with Fleiss’ Kappa (κ). Values from 0.0 to 0.2 indicate registered between the four radiologists (118 to 136 of slight agreement, 0.21 to 0.40 fair agreement, 0.41 to 155 possible lesions detected, Table 5). 0.60 moderate agreement, 0.61 to 0.80 substantial agree- ment, and values ranging from 0.81 to 1.0 indicate al- Discussion most perfect or perfect agreement [18]. Sensitivity, This study shows that the detection of metastatic lesions specificity as well as accuracy were calculated for every of ccRCC can be performed with excellent comparable radiologist and plotted on a receiver operating character- sensitivity and specificity between single PVP imaging istics (ROC)-curve. Determination of the optimal cut-off and dual, AP and PVP, imaging. point was achieved by the Youden index. After verifica- Both groups achieved a good sensitivity of 82.3% for tion of the non-Gaussian distribution of every parameter the AP + PVP group and 83.1% for the PVP only group, by the Shapiro-Wilk test, we opted for a non-parametric whereas the specificity of both groups was excellent with test (Kruskal-Wallis-H test) to analyze differences be- 98.4% and 99.5%, respectively. This resulted in a good to tween the four independent radiologists. A two-tailed p- very good interrater agreement for the ten potential value of less than 0.05 was considered to indicate statis- metastatic sides evaluated in this study. Moreover, all tical significance. four readers achieved a very good area under the ROC curves (>0.9, Table 4). Results In our cohort, 7 of the 43 patients had pancreatic me- The mean patient age at the time point of CT examin- tastases. Of these, every single radiologist detected 6 ation was 67 ± 10 years. The 27 male and 16 female pa- (86%) pancreatic lesions as such. Recent publications tients presented with a total of 155 metastatic lesions claimed that especially metastatic lesions of the pancreas (mean 3.6 metastatic lesions per patient). The majority are more easily detectable in the arterial contrast phase of lesions were solid lesions (102/155) followed by het- [11, 13]. This might be due to the early arterial enhance- erogeneous (43/155) and cystic lesions (10/155) (p= ment of pancreatic metastasis compared to parenchyma 0.001). Only 2% of the lesions presented with calcifica- [19]. Particularly, initial small sized pancreatic metasta- tions. Most of the metastatic lesions were found in the ses, which often occur metachronous several years after lungs (n = 31, 72.1%) followed by lymph node metasta- the initial diagnosis, might increase true-positive lesion ses (n = 30, 69.8%) and bone metastases, appearing detection [20]. In fact, even the radiologists who read Hagen et al. Cancer Imaging (2022) 22:9 Page 5 of 9 Fig. 2 Axial CT images of the pancreas in arterial (A) and portal venous (B) phases of a 65-year-old woman with metastatic RCC. In both phases the metastasis is visible as a hypervascularized lesion (white arrows) the PVP datasets only achieved a higher detection rate Furthermore, good interrater agreement between the than in recently published literature (86% vs. 50 – 69%) use of PVP only and the combination of PVP and AP [11]. A reason for this might be the earlier imaging time was achieved for the upper abdominal organs, especially point in our study protocol compared to Corwin et al. for detection of hepatic and renal metastases. Our re- (65 s vs. 80-90 s) [11]. In contrast to Jain et al., who re- sults reinforce the assumption that an additional AP in ported a visualization of pancreatic metastases in the the detection of ccRCC metastasis might be of limited PVP or AP datasets only of up to 25% [12], we perceived value that has been controversially discussed in the lit- all pancreatic metastases equally in both phases. Further- erature for liver metastases [12, 22]. Advances in DECT more, 4 of the 7 pancreatic metastases occurred in pa- with an improved assessment of hypodense liver lesions tients receiving no therapy. Especially targeted-therapy in the PVP by switching keV levels in monoenergetic re- results in reduced density of parenchymatous organs in constructions [23] might confirm this notion in the fu- the arterial phase of CECT [21]. These might be reasons ture. Some authors state the necessity of an AP for the for the contrast between pancreatic parenchyma and detection of renal metastases, especially for local recur- pancreatic metastasis (see Fig. 2). rence [14]. For our cohort, we cannot confirm this hy- pothesis as we found that local recurrences were Table 2 Patient characteristics detected at comparable rates in the PVP only (10 lesions Total detected in the AP+PVP group vs. 9 lesions detected for PVP only group, Table 5). Griffin et al. reported that Age [mean ± standard deviation] 67 ± 10 years local recurrences can be shown on CECT as solid en- Sex [n] 27 male and 16 female hancing masses [14]. As the contrast is higher in hyper- No treatment [n] 22 (51.2%) vascularized lesions in the AP compared to the PVP Treatment with Checkpoint inhibitor 12 (27.9%) [12], Raptopoulos et al. proposed a practical approach by (Nivolumab, Pembrolizumab+ Axitinib) [n] Treatment with tyrosine kinase inhibitor 9 (20.9%) Table 3 Sensitivity, specificity and accuracy of the 4 different (Sorafenib, Cabozantinib, Pazopanib, radiologists depending on the image data sets Sunitinib) [n] Radiologist #1 Accuracy 92.8% Metastatic lesions divided by organ 155 AP + PVP systems (total) [n] Sensitivity 85.2% Pulmonary [n] 31 (20.0%) Specificity 97.1% Lymphatic [n] 30 (19.4%) Radiologist #2 AP + PVP Accuracy 94.9% Osseous [n] 18 (11.6%) Sensitivity 79.4% Hepatic [n] 16 (10.3%) Specificity 99.6% Adrenal [n] 13 (8.4%) Radiologist #3 PVP Accuracy 93.7% Peritoneal [n] 12 (7.7%) Sensitivity 83.2% Local [n] 11 (7.1%) Specificity 99.6% Contralateral kidney [n] 9 (5.8%) Radiologist #4 PVP Accuracy 93.5% Soft tissue [n] 8 (5.2%) Sensitivity 83.1% Pancreatic [n] 7 (4.5%) Specificity 99.3% Hagen et al. Cancer Imaging (2022) 22:9 Page 6 of 9 Table 4 Area under the ROC-Curve Radiologist #1 (AP+PVP) Radiologist #2 Radiologist #3 Radiologist #4 (AP+PVP) (PVP only) (PVP only) AUC 0.918 0.901 0.922 0.913 (CI: 0.884 – 0.952) (CI: 0.863 – 0.939) (CI: 0.889 – 0.956) (CI: 0.878 – 0.949) CI: confidence interval considering an AP und PVP for initial evaluations of pa- lead to additional information for the characterization of tients with metastatic RCCs and the use of the PVP only small nodules. for follow-up examinations [24]. In our study cohort, the missed lesions would not have Pulmonary lesions are the most common site of recur- led to treatment changes as there were more than 3 rence in ccRCC [10, 13], which is in line with 72.1% of metastatic lesions present per patient. This is in line lung metastases in our cohort. Incidental pulmonary with findings reported by Jain et al. where only 2% of nodules are commonly seen on CT-scans of the chest the metastatic lesions lead to a different treatment [12]. and therefore the diagnosis of ccRCC metastasis might However, this might be of importance when only a lim- be difficult without previous examinations [25]. With ited number of metastases are present as the patients only one examination in our study, interrater agreement with oligometastatic disease are prone to metastasect- between the 4 radiologists was still decent (κ 0.6, omy instead of systemic treatment. There were no sig- Table 4). As reported by Price et al., pulmonary metasta- nificant differences when comparing the specificity ses most often appear as solid nodules and masses, between the two groups in our study (98.4% vs. 99.6%). sometimes surrounded by a peripheral ground-glass halo Three typical patterns of the metastases could be dif- [26]. However, adding more contrast phases would not ferentiated: solid, heterogeneous and cystic. As reported Fig. 3 Receiver operating characteristic (ROC) curves depending on the image protocol Hagen et al. Cancer Imaging (2022) 22:9 Page 7 of 9 Fig. 4 Coronal CT images of the local recurrence in arterial (A) and portal venous (B) phases of a 64-year-old man with multiple metastatic RCC by Smith et al., targeted therapies result in distinct pat- Limitations terns of metastatic ccRCCs as they might change their ap- This single-center study is limited by its nonrandomized pearance and enhancement pattern from an initially and retrospective design. Moreover, the lack of histo- homogeneous and non-enhancing mass [27]. This is even logical confirmation of metastases had to be compen- more important as contemporaneous reduction in tumor sated by successional CT-scans permitting the size and attenuation were correlated with favorable clinical evaluation of tissue dynamics. Another confounder may outcomes [28]. However, while no different imaging re- be the fact, that about half of the patients were currently sponse criteria are defined for assessing therapy response receiving therapy, which is likely to cause altered perfu- diameter-based criteria remain essential [29]. sion characteristics of the metastases [12]. As a result of We conclude that staging of metastatic ccRCCs using the low number of cases included, the data may have PVP only resulted in comparable results to dual-phase overestimated the potential of the portal venous contrast CECT and help to reduce radiation exposure. Taking enhanced phase for the detection of metastases. Further- the number of repetitive staging examinations into ac- more, the two “less experienced” radiologists had both count the radiation exposure can be substantially re- phases whereas the two experienced radiologists only duced, although the 5-year overall survival in metastatic had the PV phase, resulting in a certain degree of inter- ccRCC patients is limited [30, 31]. reader bias. However, by getting comparable detection Table 5 Inter-reader agreement depending on metastatic lesions Radiologist #1 Radiologist #2 Radiologist #3 Radiologist #4 Fleiss‘ p-value Kappa κ Pulmonary metastases [n] 31 24 27 27 0.60 ± 0.05 <0.001 Lymph node metastases [n] 26 20 24 23 0.61 ± 0.05 <0.001 Osseous metastases [n] 16 16 17 16 0.76 ± 0.05 <0.001 Hepatic metastases [n] 13 14 15 15 0.66 ± 0.05 <0.001 Adrenal metastases [n] 12 8 6 7 0.63 ± 0.05 <0.001 Peritoneal metastases [n] 9 8 8 8 0.83 ± 0.06 <0.001 Local recurrences [n] 10 10 9 9 0.69 ± 0.05 <0.001 Contralateral kidney [n] 6 6 5 5 0.76 ± 0.04 <0.001 Soft tissue metastases [n] 7 6 8 7 0.69 ± 0.05 <0.001 Pancreatic metastases [n] 6 6 6 6 0.66 ± 0.05 <0.001 Hagen et al. Cancer Imaging (2022) 22:9 Page 8 of 9 rates in both groups the experience seems to replace an Received: 16 June 2021 Accepted: 1 January 2022 additional AP. References Conclusions 1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J In this study, we demonstrate similar rates for detection, Cancer. 2013;49(6):1374–403. https://doi.org/10.1016/j.ejca.2012.12.027. sensitivity and specificity of metastases and local recur- 2. Bedke J, Albiges L, Capitanio U, et al. Updated European Association of rence of ccRCC when comparing a dual phase protocol Urology Guidelines on Renal Cell Carcinoma: Nivolumab plus Cabozantinib Joins Immune Checkpoint Inhibition Combination Therapies for Treatment- with arterial and portal-venous contrast to a single- naïve Metastatic Clear-Cell Renal Cell Carcinoma. Eur Urol. 2020. https://doi. phase protocol with portal-venous contrast. Considering org/10.1016/j.eururo.2020.12.005. a certain experience level, we conclude that a single- 3. Hoffmann NE, Gillett MD, Cheville JC, Lohse CM, Leibovich BC, Blute ML. Differences in organ system of distant metastasis by renal cell carcinoma phase examination might be sufficient for follow-up ex- subtype. J Urol. 2008;179(2):474–7. https://doi.org/10.1016/j.juro.2007.09.036. aminations in patients with metastatic ccRCC. 4. Vogel C, Ziegelmüller B, Ljungberg B, et al. Imaging in Suspected Renal-Cell Carcinoma: Systematic Review. Clin Genitourin Cancer. 2019;17(2):e345–55. https://doi.org/10.1016/j.clgc.2018.07.024. Abbreviations 5. Ljungberg B, Albiges L, Abu-Ghanem Y, et al. European Association of AP: Arterial phase; ccRCC: Clear cell renal cell carcinoma; CECT: Contrast- Urology Guidelines on Renal Cell Carcinoma: The 2019 Update. Eur Urol. enhanced computed tomography; CT: Computed tomography; 2019;75(5):799–810. doi:https://doi.org/10.1016/j.eururo.2019.02.011. EAU: European Association of Urology; FU: Follow-up; MRI: Magnetic 6. Liaw CW, Winoker JS, Mehrazin R. Imaging Protocols for Active Surveillance resonance imaging; PVP: Portal venous phase; RCC: Renal cell carcinoma; in Renal Cell Carcinoma. Curr Urol Rep. 2018;19(10):81. https://doi.org/10.1 ROC: Receiver operating characteristics; SD: Standard deviation 007/s11934-018-0830-z. 7. Chu JS, Wang ZJ. Protocol Optimization for Renal Mass Detection and Acknowledgements Characterization. Radiol Clin North Am. 2020;58(5):851–73. https://doi.org/1 ‘Not applicable’. 0.1016/j.rcl.2020.05.003. 8. Ali O, Fishman EK, Kawamoto S. Recurrent renal cell carcinoma following nephrectomy and ablation therapy: Radiology perspective. Eur J Radiol. Authors’ contributions 2018;107:134–42. https://doi.org/10.1016/j.ejrad.2018.05.002. FH, WT, FP, SKau analyzed and interpreted the patient data regarding the 9. Dabestani S, Marconi L, Kuusk T, Bex A. Follow-up after curative treatment metastases of the RCC. FH and WT had both a major contribution in writing of localised renal cell carcinoma. World J Urol. 2018;36(12):1953–9. https:// the manuscript. JS, AM, AS, KN, SKru and SKau revised the manuscript. All doi.org/10.1007/s00345-018-2338-z. authors read and approved the final manuscript. 10. Chae EJ, Kim JK, Kim SH, Bae S-J, Cho K-S. Renal cell carcinoma: Analysis of postoperative recurrence patterns. Radiology. 2005;234(1):189–96. https:// Funding doi.org/10.1148/radiol.2341031733. ‘Not applicable’. Open Access funding enabled and organized by Projekt 11. Corwin MT, Lamba R, Wilson M, McGahan JP. Renal cell carcinoma DEAL. We acknowledge support by Open Access Publishing Fund of metastases to the pancreas: Value of arterial phase imaging at MDCT. Acta University of Tübingen. Radiol. 2013;54(3):349–54. https://doi.org/10.1258/ar.2012.120693. 12. Jain Y, Liew S, Taylor MB, Bonington SC. Is dual-phase abdominal CT necessary for the optimal detection of metastases from renal cell Availability of data and materials carcinoma? Clin Radiol. 2011;66(11):1055–9. https://doi.org/10.1016/j.crad.2 All data generated or analysed during this study are included in this 011.06.002. published article. 13. Coquia SF, Johnson PT, Ahmed S, Fishman EK. MDCT imaging following nephrectomy for renal cell carcinoma: Protocol optimization and patterns of Declarations tumor recurrence. World J Radiol. 2013;5(11):436–45. https://doi.org/10.4329/ wjr.v5.i11.436. Ethics approval and consent to participate 14. Griffin N, Gore ME, Sohaib SA. Imaging in metastatic renal cell carcinoma. This retrospective data evaluation was approved by the institutional review AJR Am J Roentgenol. 2007;189(2):360–70. https://doi.org/10.2214/AJR.07.2 board which was assigned the approval number 197/2020BO2. Verbal and written informed consent were waived due to the retrospective nature of 15. Caruso D, Rosati E, Panvini N, et al. Optimization of contrast medium the study. Consent for publication was given by all authors. volume for abdominal CT in oncologic patients: prospective comparison between fixed and lean body weight-adapted dosing protocols. Insights Imaging. 2021;12(1):40. https://doi.org/10.1186/s13244-021-00980-0. Consent for publication 16. Itoh S, Ikeda M, Achiwa M, Satake H, Iwano S, Ishigaki T. Late-arterial and ‘Not applicable’. portal-venous phase imaging of the liver with a multislice CT scanner in patients without circulatory disturbances: automatic bolus tracking or Competing interests empirical scan delay? Eur Radiol. 2004;14(9):1665–73. https://doi.org/10.1 ‘Not applicable’. 007/s00330-004-2321-5. 17. Birnbaum BA, Jacobs JE, Langlotz CP, Ramchandani P. Assessment of a Author details bolus-tracking technique in helical renal CT to optimize nephrographic Department of Diagnostic and Interventional Radiology, phase imaging. Radiology. 1999;211(1):87–94. https://doi.org/10.1148/ra Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076 Tübingen, Germany. diology.211.1.r99ap4187. Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076 18. Landis JR, Koch GG. The measurement of observer agreement for Tübingen, Germany. Clinic of Urology, Siloah St. Trudpert Klinikum, categorical data. Biometrics. 1977;33(1):159–74. Wilferdinger Str. 67, 75179 Pforzheim, Germany. Department of Urology, 19. Tordjman M, Dbjay J, Chamouni A, et al. Clear Cell Papillary Renal Cell University Hospital of Tübingen Eberhard-Karls-University, Hoppe-Seyler-Str.3, Carcinoma: A Recent Entity With Distinct Imaging Patterns. AJR Am J 72076 Tübingen, Germany. Diagnostic and Interventional Radiology, Siloah Roentgenol. 2020;214(3):579–87. https://doi.org/10.2214/AJR.19.21681. St. Trudpert Klinikum, Wilferdinger Str. 67, 75179 Pforzheim, Germany. 20. Mechó S, Quiroga S, Cuéllar H, Sebastià C. Pancreatic metastasis of renal cell Department of Nuclear Medicine, University Hospital Ulm, carcinoma: Multidetector CT findings. Abdom Imaging. 2009;34(3):385–9. Albert-Einstein-Allee 23, 89081 Ulm, Germany. https://doi.org/10.1007/s00261-008-9391-9. Hagen et al. Cancer Imaging (2022) 22:9 Page 9 of 9 21. Nathan PD, Vinayan A, Stott D, Juttla J, Goh V. CT response assessment combining reduction in both size and arterial phase density correlates with time to progression in metastatic renal cancer patients treated with targeted therapies. Cancer Biol Ther. 2010;9(1):15–9. https://doi.org/10.4161/ cbt.9.1.10340. 22. Francis IR, Cohan RH, McNulty NJ, et al. Multidetector CT of the liver and hepatic neoplasms: Effect of multiphasic imaging on tumor conspicuity and vascular enhancement. AJR Am J Roentgenol. 2003;180(5):1217–24. https:// doi.org/10.2214/ajr.180.5.1801217. 23. Caruso D, Cecco CN de, Schoepf UJ, et al. Can dual-energy computed tomography improve visualization of hypoenhancing liver lesions in portal venous phase? Assessment of advanced image-based virtual monoenergetic images. Clin Imaging. 2017;41:118–24. https://doi.org/10.101 6/j.clinimag.2016.10.015. 24. Raptopoulos VD, Blake SP, Weisinger K, Atkins MB, Keogan MT, Kruskal JB. Multiphase contrast-enhanced helical CT of liver metastases from renal cell carcinoma. Eur Radiol. 2001;11(12):2504–9. https://doi.org/10.1007/s0033001 25. Blagev DP, Lloyd JF, Conner K, et al. Follow-up of incidental pulmonary nodules and the radiology report. J Am Coll Radiol. 2014;11(4):378–83. https://doi.org/10.1016/j.jacr.2013.08.003. 26. Price M, Wu CC, Genshaft S, et al. Imaging and Management of Intrathoracic Renal Cell Carcinoma Metastases. AJR Am J Roentgenol. 2018; 210(6):1181–91. https://doi.org/10.2214/AJR.18.19645. 27. Smith AD, Lieber ML, Shah SN. Assessing tumor response and detecting recurrence in metastatic renal cell carcinoma on targeted therapy: Importance of size and attenuation on contrast-enhanced CT. AJR Am J Roentgenol. 2010;194(1):157–65. https://doi.org/10.2214/AJR.09.2941. 28. Thian Y, Gutzeit A, Koh D-M, et al. Revised Choi imaging criteria correlate with clinical outcomes in patients with metastatic renal cell carcinoma treated with sunitinib. Radiology. 2014;273(2):452–61. https://doi.org/10.114 8/radiol.14132702. 29. Schwartz LH, Litière S, Vries E de, et al. RECIST 1.1-Update and clarification: From the RECIST committee. Eur J Cancer. 2016;62:132–7. https://doi.org/1 0.1016/j.ejca.2016.03.081. 30. Rini BI, Powles T, Atkins MB, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. The Lancet. 2019;393(10189):2404–15. https://doi.org/10.101 6/S0140-6736(19)30723-8. 31. Méjean A, Ravaud A, Thezenas S, et al. Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma. N Engl J Med. 2018;379(5): 417–27. https://doi.org/10.1056/NEJMoa1803675. Publisher’sNote Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Journal

Cancer Imaging – Springer Journals

Published: Jan 21, 2022

Keywords: Arterial contrast phase; Image quality; Interreader-agreement; Portal venous contrast phase; Renal cell carcinoma

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