CT prediction of surgical outcome in patients with advanced epithelial ovarian carcinoma undergoing neoadjuvant chemotherapy.

OBJECTIVE: A scoring system has been proposed to predict gross residual disease at primary debulking surgery (PDS) for advanced epithelial ovarian cancer. This scoring system has not been assessed in patients undergoing neoadjuvant chemotherapy (NACT). The aim of this study is to assess the reproducibility and prognostic significance of the scoring system when applied to women undergoing NACT followed by interval debulking surgery (IDS). METHODS: A retrospective cohort study was conducted of patients with advanced ovarian cancer who underwent NACT and IDS between 2005 and 2014. Change in tumor burden using computed tomography (CT) at diagnosis (T0) and after initiation of NACT but before IDS (T1) was independently assessed by two radiologists blinded to outcomes using two read criteria: a scoring system utilizing clinical and radiologic criteria and RECIST 1.1. Relationship between CT assessments to surgical outcome, progression free survival (PFS) and overall survival (OS) were evaluated. Reader agreement was measured using Fleiss's kappa (ĸ). RESULTS: 76 patients were analyzed. Optimal surgical outcome was achieved in 69 (91%) of patients. Median progression free survival was 13.2 months and overall survival was 32.6 months, respectively. Predictive score change from T0 to T1 of >1 (denoting an improvement in disease burden) was associated with optimal cytoreduction (p = 0.02 and 0.01 for readers 1 and 2, respectively). Neither predictive score nor RECIST 1.1 assessment was predictive of OS or PFS. Reader agreement was substantial for predictive score (κ = 0.77) and moderate for RECIST (κ = 0.51) assessments. CONCLUSIONS: A change in score before and after neoadjuvant chemotherapy minimizes reader variability and predicts surgical outcome.

Atypical Response Patterns in Patients Treated With Nivolumab.

OBJECTIVE. The purpose of this study is to assess the frequency of atypical response patterns in oncology patients treated with the programmed cell death protein-1 inhibitor nivolumab. MATERIALS AND METHODS. This retrospective study included 254 patients treated with nivolumab alone or in combination, from January 2013 through August 2017. A blinded reader prospectively assessed treatment response. Among 166 patients (65%) who experienced a clinical benefit (defined as stable disease, partial response, or complete response as the best response), four response patterns were identified: pattern 1 is a decrease or less than 20% increase in the sum of the longest dimension (SLD) without a return to below the nadir, pattern 2 is a 10-19% increase in SLD with a return to below the nadir, pattern 3 is a 20% or greater increase in SLD with a return to below the nadir (classic pseudoprogression), and pattern 4 is the development of new lesions with a decrease in SLD lasting through at least two consecutive scans. Patterns 2, 3, and 4 were defined as atypical response patterns. RESULTS. Of 166 patients who experienced a clinical benefit, pattern 1 was seen in 133 (80%), pattern 2 was seen in 15 (9%), pattern 3 was seen in two (1%), and pattern 4 was seen in 16 (10%) patients. Thus, atypical response patterns were seen in 33 (20%) patients who experienced a clinical benefit, including 25 of 91 (27%) taking nivolumab and ipilimumab combined, six of 46 (13%) taking nivolumab alone, and two of 29 (7%) taking a combination of nivolumab and another chemotherapeutic agent (p = 0.02). CONCLUSION. Although classic pseudoprogression was rare, an atypical response was seen in 20% of patients who experienced a clinical benefit, and a delayed response up to 24 months of therapy may be seen. Radiologists should be aware of these atypical patterns to avoid errors in response assessment.

Immune Checkpoint Inhibitor Cancer Therapy: Spectrum of Imaging Findings.

Immune checkpoint inhibitors are a new class of cancer therapeutics that have demonstrated striking successes in a rapid series of clinical trials. Consequently, these drugs have dramatically increased in clinical use since being first approved for advanced melanoma in 2011. Current indications in addition to melanoma are non-small cell lung cancer, head and neck squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma, and classical Hodgkin lymphoma. A small subset of patients treated with immune checkpoint inhibitors undergoes an atypical treatment response pattern termed pseudoprogression: New or enlarging lesions appear after initiation of therapy, thereby mimicking tumor progression, followed by an eventual decrease in total tumor burden. Traditional response standards applied at the time of initial increase in tumor burden can falsely designate this as treatment failure and could lead to inappropriate termination of therapy. Currently, when new or enlarging lesions are observed with immune checkpoint inhibitors, only follow-up imaging can help distinguish patients with pseudoprogression from the large majority in whom this observation represents true treatment failure. Furthermore, the unique mechanism of immune checkpoint inhibitors can cause a distinct set of adverse events related to autoimmunity, which can be severe or life threatening. Given the central role of imaging in cancer care, radiologists must be knowledgeable about immune checkpoint inhibitors to correctly assess treatment response and expeditiously diagnose treatment-related complications. The authors review the molecular mechanisms and clinical applications of immune checkpoint inhibitors, the current strategy to distinguish pseudoprogression from progression, and the imaging appearances of common immune-related adverse events. ©RSNA, 2017.

Imaging features and metastatic pattern of non-IVC retroperitoneal leiomyosarcomas: are they different from IVC leiomyosarcomas?

PURPOSE: The purposes of this study were to describe the imaging features and metastatic pattern of non-inferior vena cava (IVC) retroperitoneal leiomyosarcomas (non-IVC LMS) and to compare them with those of IVC leiomyosarcomas (IVC LMS) to assess any differences between the 2 groups. MATERIALS AND METHODS: In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, all 56 patients with pathologically confirmed primary retroperitoneal leiomyosarcoma (34 non-IVC LMS and 22 IVC LMS) seen at our tertiary cancer center during a 10-year period were included. All available imaging of primary tumor (18 non-IVC LMS and 19 IVC LMS) and follow-up imaging studies (on all 56 patients) were reviewed in consensus by 2 fellowship-trained oncoradiologists. Imaging features and metastatic spread of non-IVC LMS were described and compared with those of IVC LMS. Continuous variables were compared using the Student t test, binary variables with the Fisher exact test, and survival using the log-rank test. RESULTS: Non-inferior vena cava retroperitoneal leiomyosarcomas had a mean size of 11.3 cm (range, 3.7-27 cm) and most commonly occurred in the perirenal space (16/18). Primary tumors were hyperattenuating to muscle (11/18) and showed heterogeneous enhancement (17/18). Lungs (22/34), peritoneum (18/34), and liver (18/34) were the most common metastatic sites. There was no significant difference between the imaging features and metastatic pattern of non-IVC and IVC LMS. Although non-IVC LMS presented at a more advanced stage (P < 0.002), there was statistically non-significant trend toward better median survival of non-IVC LMS (P = 0.07). CONCLUSIONS: Non-inferior vena cava retroperitoneal leiomyosarcomas are large heterogeneous tumors arising in the perirenal space and frequently metastasize to lungs, peritoneum, and liver. From a radiologist's perspective, non-IVC LMS behave similar to IVC-LMS.

MRI, MDCT features, and clinical outcome of extremity leiomyosarcomas: experience in 47 patients.

OBJECTIVE: To describe MRI, MDCT features, and clinical outcome of extremity leiomyosarcomas (LMS). MATERIALS AND METHODS: In this IRB-approved, HIPAA-compliant retrospective study, we included 47 patients (23 women, 24 men; mean age: 55.3 years, range: 17-85 years) with pathologically confirmed extremity LMS seen at our adult tertiary cancer center between 2000 and 2012. MRI/MDCT of primary tumors in 23 patients and follow-up in all patients were reviewed by two radiologists in consensus. Clinical data were extracted from electronic medical records. RESULTS: Primary tumors were distributed in bones (6 out of 47), deep soft tissues (24 out of 47), and superficial soft tissues (17 out of 47). On imaging (bone = 4, deep soft tissue = 11, superficial soft tissue = 8), compared with skeletal muscle, they were T1 iso-hypointense and T2 hyperintense. Bone LMS were metaphyseal tumors with cortical destruction (3 out of 4). Deep soft-tissue LMS were large with hemorrhage (7 out of 11) and necrosis (10 out of 11). Superficial soft-tissue LMS were relatively smaller, homogeneously enhancing (6 out of 8) tumors. Distant metastases developed in 32 out of 47 patients (bone LMS [6 out of 6], deep soft-tissue LMS [18 out of 24], superficial soft-tissue LMS [8 out of 17]), commonly to lung (29 out of 47) and bone (14 out of 47). At the time of writing, 22 out of 36 patients (bone LMS [4 out of 6], deep soft-tissue LMS [15 out of 24], superficial soft-tissue LMS [4 out of 17]) have died. There was no statistically significant correlation between metastatic disease and tumor size or grade. CONCLUSION: Extremity LMS arise in bones and in the deep and superficial soft tissues, frequently metastasize to the lungs, and have a poor prognosis. Superficial LMS tend to have a better prognosis than bone or deep soft-tissue LMS.

MRI for evaluation of myeloid sarcoma in adults: a single-institution 10-year experience.

OBJECTIVE: The purpose of this study was to evaluate the utilization and role of MRI in the management of myeloid sarcoma in adults. MATERIALS AND METHODS: A retrospective study of 69 patients with pathologically proven myeloid sarcoma included 25 patients (16 men, nine women; mean age, 55 years; range, 22-78 years) who underwent pretreatment MRI at our institution from January 2001 to October 2011. A total of 71 MRI examinations were evaluated by two radiologists in consensus. RESULTS: A total of 41 sites of involvement of myeloid sarcoma were noted, most commonly bone (13/25, 52%), muscle (7/25, 28%), CNS (6/25, 24%), and head and neck (6/25, 24%). Nineteen sites were noted on MR images obtained for evaluation of a new sign or symptom, most commonly musculoskeletal (11 sites) and CNS (six sites). Fifteen sites were noted on MR images obtained for further evaluation of a previously detected abnormality, most commonly in the abdomen and pelvis (seven sites). Seven lesions were incidentally found on MR images obtained for other myeloid sarcoma-related indications, most commonly in the head and neck (three lesions) and musculoskeletal system (three lesions). The mean size of measurable lesions was 5.6 cm (range, 1-20 cm). Compared with muscle, the lesions were isointense (31/41, 75.6%) or hypointense (10/41, 24.4%) on T1-weighted images and mildly hyperintense (39/41, 95.1%) on T2-weighted images and had homogeneous enhancement (29/38, 76.3%). CONCLUSION: In our experience, MRI was most often used for evaluation of bone, muscle, the CNS, and the head and neck region. MRI is useful for evaluation of new musculoskeletal and CNS findings and for further evaluation of known abdominopelvic masses. Incidental findings are often musculoskeletal or in the soft tissues of the head and neck.

Abdominal immune-related adverse events: detection on ultrasonography, CT, MRI and 18F-Fluorodeoxyglucose positron emission tomography.

Immune checkpoint inhibitor and chimeric antigen receptor T-cell therapies are associated with a unique spectrum of complications termed immune-related adverse events (irAEs). The abdomen is the most frequent site of severe irAEs that require hospitalization with life-threatening consequences. Most abdominal irAEs such as enterocolitis, hepatitis, cholangiopathy, cholecystitis, pancreatitis, adrenalitis, and sarcoid-like reaction are initially detected on imaging such as ultrasonography (US), CT, MRI and fusion 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT during routine surveillance of cancer therapy. Early recognition and diagnosis of irAEs and immediate management with cessation of immune modulator cancer therapy and institution of immunosuppressive therapy are necessary to avert morbidity and mortality. Diagnosis of irAEs is confirmed by tissue sampling or by follow-up imaging demonstrating resolution. Abdominal radiologists reviewing imaging on patients being treated with anti-cancer immunomodulators should be familiar with the imaging manifestations of irAEs.

Comparison of performance of various tumour response criteria in assessment of regorafenib activity in advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib.

PURPOSE: To compare performance of various tumour response criteria (TRCs) in assessment of regorafenib activity in patients with advanced gastrointestinal stromal tumour (GIST) with prior failure of imatinib and sunitinib. METHODS: Twenty participants in a phase II trial received oral regorafenib (median duration 47 weeks; interquartile range (IQR) 24-88) with computed tomography (CT) imaging at baseline and every two months thereafter. Tumour response was prospectively determined on using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, and retrospectively reassessed for comparison per RECIST 1.0, World Health Organization (WHO) and Choi criteria, using the same target lesions. Clinical benefit rate [CBR; complete or partial response (CR or PR) or stable disease (SD)≥16 weeks] and progression-free survival (PFS) were compared between various TRCs using kappa statistics. Performance of TRCs in predicting overall survival (OS) was compared by comparing OS in groups with progression-free intervals less than or greater than 20 weeks by each TRC using c-statistics. RESULTS: PR was more frequent by Choi (90%) than RECIST 1.1, RECIST 1.0 and WHO (20% each), however, CBR was similar between various TRCs (overall CBR 85-90%, 95-100% agreement between all TRC pairs). PFS per RECIST 1.0 was similar to RECIST 1.1 (median 44 weeks versus 58 weeks), and shorter for WHO (median 34 weeks) and Choi (median 24 weeks). With RECIST 1.1, RECIST 1.0 and WHO, there was moderate concordance between PFS and OS (c-statistics 0.596-0.679). Choi criteria had less favourable concordance (c-statistic 0.506). CONCLUSIONS: RECIST 1.1 and WHO performed somewhat better than Choi criteria as TRC for response evaluation in patients with advanced GIST after prior failure on imatinib and sunitinib.

Typical and atypical metastatic sites of recurrent endometrial carcinoma.

The purpose of this article is to illustrate the imaging findings of typical and atypical metastatic sites of recurrent endometrial carcinoma. Typical sites include local pelvic recurrence, pelvic and para-aortic nodes, peritoneum, and lungs. Atypical sites include extra-abdominal lymph nodes, liver, adrenals, brain, bones and soft tissue. It is important for radiologists to recognize the typical and atypical sites of metastases in patients with recurrent endometrial carcinoma to facilitate earlier diagnosis and treatment.

Pre-procedural imaging of aortic root orientation and dimensions: comparison between X-ray angiographic planar imaging and 3-dimensional multidetector row computed tomography.

OBJECTIVES: We sought to examine whether contrast-enhanced multidetector row computed tomography (MDCT) allows prediction of X-ray angiographic planes for the root angiogram in the context of transcatheter aortic valve implantation. BACKGROUND: Understanding of aortic root orientation relative to the body axis is critical for precise positioning of the stent/valve during transcatheter aortic valve implantation. METHODS: Forty patients with severe aortic stenosis underwent conventional X-ray angiography and contrast-enhanced MDCT of the aortic root. Oblique MDCT images of the aortic root, corresponding to X-ray angiographic left anterior oblique (LA)/right anterior oblique (RAO) projections, were created. The cranial/caudal angulation was compared between angiographic and reformatted MDCT images. In addition, root diameter measurements were compared. RESULTS: The cranial angulation in the LAO X-ray angiograms (mean LAO: 39+/- 8, n = 38) and matched MDCT images were not significantly different (cranial: 25 +/- 7 vs. 23 +/- 8; p = 0.214). There was a small but significant difference between the caudal angulation in the RAO angiogram (mean RAO: 25 +/- 5, n = 40) and matched CT images (caudal: 21 +/- 9 vs. 29 +/- 10; p = 0.002). The annulus diameter in the LAO projection was not significantly different between X-ray angiography and contrast-enhanced MDCT (2.3 +/- 0.3 vs. 2.4 +/- 0.3; p = 0.052), whereas there was a small but significant difference in the annulus diameter in RAO projections between angiography and MDCT (2.4 +/- 0.3 vs. 2.2 +/- 0.3; p = 0.029). CONCLUSIONS: Pre-procedural contrast-enhanced MDCT imaging of the aortic root allows prediction of X-ray angiographic planes and contributes to planning of the transcatheter aortic valve implantation.

Extent of thoracic aortic atheroma burden and long-term mortality after cardiothoracic surgery: a computed tomography study.

OBJECTIVES: We hypothesized that the extent of aortic atheroma of the entire thoracic aorta, determined by pre-operative multidetector-row computed tomographic angiography (MDCTA), is associated with long-term mortality following nonaortic cardiothoracic surgery. BACKGROUND: In patients evaluated for cardiothoracic surgery, presence of severe aortic atheroma is associated with adverse short- and long-term post-operative outcome. However, the relationship between aortic plaque burden and mortality remains unknown. METHODS: We reviewed clinical and imaging data from all patients who underwent electrocardiographic-gated contrast-enhanced MDCTA prior to coronary bypass or valvular heart surgery at our institution between 2002 and 2008. MDCTA studies were analyzed for thickness and circumferential extent of aortic atheroma in 5 segments of the thoracic aorta. A semiquantitative total plaque-burden score (TPBS) was calculated by assigning a score of 1 to 3 to plaque thickness and to circumferential plaque extent. When combined, this resulted in a score of 0 to 6 for each of the 5 segments and, hence, an overall score from 0 to 30. The primary end point was all-cause mortality during long-term follow-up. RESULTS: A total of 862 patients (71% men, 67.8 years) were included and followed over a mean period of 25 ± 16 months. The mean TPBS was 8.6 (SD: ±6.0). The TPBS was a statistically significant predictor of mortality (p < 0.0001) while controlling for baseline demographics, cardiovascular risk factors, and type of surgery including reoperative status. The estimated hazard ratio for TPBS was 1.08 (95% confidence interval: 1.045 to 1.12). Other independent predictors of mortality were glomerular filtration rate (p = 0.015), type of surgery (p = 0.007), and peripheral artery disease (p = 0.03). CONCLUSIONS: Extent of thoracic aortic atheroma burden is independently associated with increased long-term mortality in patients following cardiothoracic surgery. Although our data do not provide definitive evidence, they suggest a relationship to the systemic atherosclerotic disease process and, therefore, have important implications for secondary prevention in post-operative rehabilitation programs.

Aortic root morphology in patients undergoing percutaneous aortic valve replacement: evidence of aortic root remodeling.

OBJECTIVE: Percutaneous aortic valve replacement is an emerging therapy for selected patients with severe aortic stenosis. Preoperative imaging of the aortic root facilitates sizing and deployment of the percutaneous aortic valve replacement device. We compared morphologic characteristics of the aortic root in patients with aortic stenosis versus elderly gender-matched controls using multidetector computed tomography. METHODS: Twenty-five consecutive subjects with severe calcific aortic stenosis referred for percutaneous aortic valve replacement and 25 elderly gender-matched controls were scanned on a Siemens Definition Dual Source (Siemens Medical, Forchheim, Germany) multidetector computed tomography scanner. Distances from the valve annulus to the coronary artery ostia and sinotubular junction, dimensions of the aortic root, and characteristics of the valve cusps were determined. RESULTS: Subjects with aortic stenosis had reduced distance from the aortic valve annulus to the inferior margins of the left and right coronary artery ostium and sinotubular junction compared with controls. There were no significant differences in cross-sectional dimensions of the aortic root. CONCLUSION: The distance from the aortic valve annulus to the coronary artery ostia and sinotubular junction is reduced in patients with aortic stenosis compared with controls. This finding suggests that longitudinal remodeling of the aortic root occurs in calcific aortic stenosis and has implications for the design and deployment of percutaneous aortic valve replacement devices.

Effects of surgical ventricular restoration on left ventricular contractility assessed by a novel contractility index in patients with ischemic cardiomyopathy.

A pressure-normalized left ventricular (LV) wall stress (dsigma*/dt(max)) was recently reported as a load-independent index of LV contractility. We hypothesized that this novel contractility index might demonstrate improvement in LV contractile function after surgical ventricular restoration (SVR) using magnetic resonance imaging. A retrospective analysis of magnetic resonance imaging data of 40 patients with ischemic cardiomyopathy who had undergone coronary artery bypass grafting with SVR was performed. LV volumes, ejection fraction, global systolic and diastolic sphericity, and dsigma*/dt(max) were calculated. After SVR, a decrease was found in end-diastolic and end-systolic volume indexes, whereas LV ejection fraction increased from 26% +/- 7% to 31% +/- 10% (p <0.001). LV mass index and peak normalized wall stress were decreased, whereas the sphericity index (SI) at end-diastole increased, indicating that the left ventricle became more spherical after SVR. LV contractility index dsigma*/dt(max) improvement (from 2.69 +/- 0.74 to 3.23 +/- 0.73 s(-1), p <0.001) was associated with shape change as evaluated by the difference in SI between diastole and systole (r = 0.32, p <0.001, preoperative; r = 0.23, p <0.001, postoperative), but not with baseline LV SI. In conclusion, SVR excludes akinetic LV segments and decreases LV wall stress. Despite an increase in sphericity, LV contractility, as determined by dsigma*/dt(max), actually improves. A complex interaction of LV maximal flow rate and LV mass may explain the improvement in LV contractility after SVR. Because dsigma*/dt(max) can be estimated from simple noninvasive measurements, this underscores its clinical utility for assessment of contractile function with therapeutic intervention.

Prevalence of significant peripheral artery disease in patients evaluated for percutaneous aortic valve insertion: Preprocedural assessment with multidetector computed tomography.

OBJECTIVES: Percutaneous aortic valve insertion is an emerging treatment option for selected patients with severe aortic stenosis and may be done from a transfemoral or transapical approach. Concomitant atherosclerotic peripheral artery disease limits transfemoral access. We evaluated the potential role of multidetector computed tomography in preoperative assessment of vascular anatomy. METHODS: Consecutive patients with severe aortic stenosis were included. Contrast-enhanced computed tomographic angiography of the thoracic and abdominal aorta and iliofemoral arteries was performed. Criteria of unfavorable iliofemoral anatomy were defined as a minimal luminal diameter of the common iliac, external iliac, or common femoral arteries of less than 8 mm, presence of greater than 60% circumferential calcification at the external-internal iliac bifurcation, and severe angulation between the common and external iliac arteries (< 90 degrees ). The prevalence of these criteria was evaluated and infrarenal aortic and iliofemoral arterial anatomy was compared in the groups with and without peripheral artery disease for any of these criteria. RESULTS: One hundred patients (79 +/- 9 years, 59% male) were included. A total of 35 (35%) patients had at least one criterion of unsuitable iliofemoral anatomy, including 27 patients with small minimal luminal diameter (<8 mm), 12 patients with severe circumferential calcification at the iliac bifurcation (>60%), and 4 with severe angulation of the iliac arteries (<90 degrees ). CONCLUSIONS: Significant atherosclerotic peripheral artery disease is common in the high-risk patient population currently evaluated for percutaneous aortic valve insertion. Computed tomography allows identification of patients with iliofemoral anatomy unfavorable for the transfemoral approach to percutaneous aortic valve insertion.