COVID-19 in patients with cancer: can baseline radiologic severity and early evolution predict clinical outcomes?

OBJECTIVE: To determine whether the degree of parenchymal involvement on chest radiograph (CXR) at the time of COVID-19 diagnosis and its early radiologic evolution can predict adverse events including hospitalization, intubation, and death in patients with cancer. METHODS: Retrospective study of 627 COVID-19-positive patients between March and April 2020, of which 248 had baseline CXR within 72 h of diagnosis and 64 patients had follow-up wihtin72 h. CXRs were classified as abnormal (i.e., radiologic findings suggestive of COVID-19 infection were noted), normal, or indeterminate. Baseline and follow-up severity scores were calculated based on lung regions in abnormal CXRs. Statistical analysis was performed to determine associations between abnormal CXR or severity score with adverse events. RESULTS: Of 248 patients (median age = 65) with a baseline CXR, 172/248 (69%) had an abnormal baseline study, which was associated with hospitalization (p < 0.001), intubation (p = 0.001), and death (p = 0.005). For patients with solid neoplasms, when adjusted for stage, it was associated with hospitalization (p = 0.0002), intubation (p = 0.019), and death (p = 0.03). The median baseline severity score was 3 (range = 1-10); the greater the score, the higher the likelihood of adverse outcome (p < 0.003 for all). A baseline severity score > 9 predicted > 50% probability of intubation and a score of ≥ 10 predicted > 50% of probability of death. The baseline severity score was not correlated with cancer-related treatment. Early radiologic progression was not correlated with hospitalization, intubation, or death. CONCLUSION: The degree of parenchymal involvement on CXR within 72 h of COVID-19 diagnosis is associated with adverse outcomes in patients with cancer. KEY POINTS: • In patients with cancer, the presence and severity of radiologic manifestation of COVID-19 on chest radiographs within 72 h of COVID-19 diagnosis are associated with hospitalization, intubation, and death. • Early radiologic progression on chest radiographs is not correlated with adverse outcomes.

Emergency room imaging in patients with genitourinary cancers: analysis of the spectrum of CT findings and their relation to patient outcomes.

PURPOSE: To assess the spectrum of computed tomography (CT) findings in patients with genitourinary cancers visiting the emergency room (ER) and evaluate the relationship between CT findings and overall survival (OS). METHODS: Retrospective analysis of consecutive patients with genitourinary cancers undergoing CT during an ER visit at a tertiary cancer center during a 20-month period. CTs were considered positive if there were findings relevant to the presenting complaint(s). Demographic/clinical variables were recorded. OS was evaluated using Kaplan-Meier curves. Univariate and multivariate Cox proportional hazards regression (HR) was used to evaluate OS predictors. RESULTS: Two hundred twenty-seven patients (243 visits) were included. The most common primary tumors were prostate (121 [49.8%]), bladder/urothelial (78 [32.1%]), and renal (69 [28.4%]). Common presenting complaints were abdominal pain (67 [27.6%]), respiratory symptoms (49 [20.2%]), neurological signs (37 [15.2%]), and fever (34 [14.0%]). CT findings were positive in 172 patients (70.8%) and included new/increased metastases (21.4% [52/243]), fluid collections (7.4% [18/243]), urinary tract infection/inflammation (6.2% [15/243]), enteritis/colitis (5.3% [13/243]), and pneumonia (4.9% [12/243]). A positive ER CT was associated with patient admission (p = 0.01). At multivariate analysis, independently predictive factors of shorter survival were positive ER CT (HR = 2.09 [95% CI 1.16-3.76, p = 0.01), hospital admission (HR = 2.17 [95% CI 1.38-3.41], p < 0.01), and recent systemic treatment (HR = 2.10 [95% CI 1.32-3.35], p < 0.01). CONCLUSION: When CT was performed, it was able to identify a structural cause for the presenting complaint in the majority of patients with genitourinary cancers attending the ER. A positive ER CT was associated with hospital admission and poorer overall survival.

Quantification of Iodine Concentration Using Single-Source Dual-Energy Computed Tomography in a Calf Liver.

OBJECTIVE: To evaluate the accuracy of single-source dual-energy computed tomography (ssDECT) in iodine quantification using various segmentation methods in an ex vivo model. METHODS: Ten sausages, injected with variable quantities of iodinated contrast, were inserted into 2 livers and scanned with ssDECT. Material density iodine images were reconstructed. Three radiologists segmented each sausage. Iodine concentration, volume, and absolute quantity were measured. Agreement between the measured and injected iodine was assessed with the concordance correlation coefficient (CCC). Intrareader agreement was assessed using the intraclass correlation coefficient (ICC). RESULTS: Air bubbles were observed in sausage (IX). Sausage (X) was within the same view as hyper-attenuating markers used for localization. With IX and X excluded, CCC and ICC were greater than 0.98 and greater than 0.88. When included, CCC and ICC were greater than 0.94 and greater than 0.79. CONCLUSIONS: Iodine quantification was reproducible and precise. However, accuracy reduced in sausages consisting of air filled cavities and within the same view as hyperattenuating markers.

Epworth sleepiness scale scores and adverse pregnancy outcomes.

PURPOSE: Snoring is associated with adverse pregnancy outcomes including gestational hypertensive disorders, gestational diabetes, and Cesarean deliveries. The purpose of this study was to assess whether excessive daytime sleepiness (EDS) assessed by Epworth Sleepiness Scale (ESS) increases the risk of these complications further. METHODS: Following institutional review board approval and informed consent, English-speaking women in the immediate postpartum period were systematically selected and recruited. Women answered a survey that included questions regarding symptoms of sleep-disordered breathing (SDB) using the multivariable apnea prediction index and excessive daytime sleepiness using ESS. Pregnancy and fetal outcomes were collected by review of medical records. Standard statistical analysis with multivariable logistic regression was performed. ESS was evaluated both as a continuous variable and with various cutoffs given that pregnant women are likely more sleepy at baseline than the general population. RESULTS: In patients who underwent planned Cesarean delivery, mean ESS was significantly higher than in those with uncomplicated vaginal delivery, even after adjusting for confounders (adjusted odds ratio (aOR), 1.08; 95 % CI, 1.01-1.15; p = 0.02). There was no significant association between EDS (defined as ESS of >10) and gestational diabetes or gestational hypertensive disorders in snorers or non snorers. However, a significant association with gestational diabetes was found in patients with an ESS of >16 compared to those with an ESS of ≤16, even after multiple adjustments (aOR, 6.82; 95 % CI, 1.19-39.27), but the number of subjects in an ESS of >16 category was small. CONCLUSIONS: There is an increased association between women with higher ESS and planned Cesarean delivery. Severe EDS was associated with gestational diabetes in pregnant women in a small sample size. Future studies in larger samples need to confirm the association of severe EDS and gestational diabetes and elucidate potential mechanisms of the links with adverse outcomes.

The GENIE BPC NSCLC Cohort: A Real-World Repository Integrating Standardized Clinical and Genomic Data for 1,846 Patients with Non-Small Cell Lung Cancer.

PURPOSE: We describe the clinical and genomic landscape of the non-small cell lung cancer (NSCLC) cohort of the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC). EXPERIMENTAL DESIGN: A total of 1,846 patients with NSCLC whose tumors were sequenced from 2014 to 2018 at four institutions participating in AACR GENIE were randomly chosen for curation using the PRISSMM data model. Progression-free survival (PFS) and overall survival (OS) were estimated for patients treated with standard therapies. RESULTS: In this cohort, 44% of tumors harbored a targetable oncogenic alteration, with EGFR (20%), KRAS G12C (13%), and oncogenic fusions (ALK, RET, and ROS1; 5%) as the most frequent. Median OS (mOS) on first-line platinum-based therapy without immunotherapy was 17.4 months [95% confidence interval (CI), 14.9-19.5 months]. For second-line therapies, mOS was 9.2 months (95% CI, 7.5-11.3 months) for immune checkpoint inhibitors (ICI) and 6.4 months (95% CI, 5.1-8.1 months) for docetaxel ± ramucirumab. In a subset of patients treated with ICI in the second-line or later setting, median RECIST PFS (2.5 months; 95% CI, 2.2-2.8) and median real-world PFS based on imaging reports (2.2 months; 95% CI, 1.7-2.6) were similar. In exploratory analysis of the impact of tumor mutational burden (TMB) on survival on ICI treatment in the second-line or higher setting, TMB z-score harmonized across gene panels was associated with improved OS (univariable HR, 0.85; P = 0.03; n = 247 patients). CONCLUSIONS: The GENIE BPC cohort provides comprehensive clinicogenomic data for patients with NSCLC, which can improve understanding of real-world patient outcomes.

Prospective testing of clinical Cerenkov luminescence imaging against standard-of-care nuclear imaging for tumour location.

In oncology, the feasibility of Cerenkov luminescence imaging (CLI) has been assessed by imaging superficial lymph nodes in a few patients undergoing diagnostic 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). However, the weak luminescence signal requires the removal of ambient light. Here we report the development of a clinical CLI fiberscope with a lightproof enclosure, and the clinical testing of the setup using five different radiotracers. In an observational prospective trial (ClinicalTrials.gov identifier NCT03484884 ) involving 96 patients with existing or suspected tumours, scheduled for routine clinical FDG PET or 131I therapy, the level of agreement of CLI with standard-of-care imaging (PET or planar single-photon emission CT) for tumour location was 'acceptable' or higher (≥3 in the 1-5 Likert scale) for 90% of the patients. CLI correlated with the concentration of radioactive activity, and captured therapeutically relevant information from patients undergoing targeted radiotherapy or receiving the alpha emitter 223Ra, which cannot be feasibly imaged clinically. CLI could supplement radiological scans, especially when scanner capacity is limited.

Systemic and Oligo-Acquired Resistance to PD-(L)1 Blockade in Lung Cancer.

PURPOSE: Clinical patterns and the associated optimal management of acquired resistance to PD-(L)1 blockade are poorly understood. EXPERIMENTAL DESIGN: All cases of metastatic lung cancer treated with PD-(L)1 blockade at Memorial Sloan Kettering were reviewed. In acquired resistance (complete/partial response per RECIST, followed by progression), clinical patterns were distinguished as oligo (OligoAR ≤ 3 lesions of disease progression) or systemic (sAR). We analyzed the relationships between patient characteristics, burden/location of disease, outcomes, and efficacy of therapeutic interventions. RESULTS: Of 1,536 patients, 312 (20%) had an initial response and 143 developed AR (9% overall, 46% of responders). OligoAR was the most common pattern (80/143, 56%). Baseline tumor mutational burden, depth of response, and duration of response were significantly increased in oligoAR compared with sAR (P < 0.001, P = 0.03, P = 0.04, respectively), whereas baseline PD-L1 and tumor burden were similar. Post-progression, oligoAR was associated with improved overall survival (median 28 months vs. 10 months, P < 0.001) compared with sAR. Within oligoAR, post-progression survival was greater among patients treated with locally-directed therapy (e.g., radiation, surgery; HR, 0.41; P = 0.039). Fifty-eight percent of patients with oligoAR treated with locally-directed therapy alone are progression-free at last follow-up (median 16 months), including 13 patients who are progression-free more than 2 years after local therapy. CONCLUSIONS: OligoAR is a common and distinct pattern of acquired resistance to PD-(L)1 blockade compared with sAR. OligoAR is associated with improved post-progression survival and some cases can be effectively managed with local therapies with durable benefit.

Ribociclib and everolimus in well-differentiated foregut neuroendocrine tumors.

The mammalian target of rapamycin inhibitor everolimus is an established therapy for well-differentiated (WD) foregut neuroendocrine tumors (NETs). Pre-clinical data demonstrates a potential synergistic role for cyclin dependent kinase 4/6 inhibition and everolimus to treat this disease. In this phase II multicenter study, patients with advanced foregut WDNETs received combination ribociclib and everolimus until confirmed disease progression or unacceptable toxicity. The first 12 patients received ribociclib 300 mg three weeks in a row with a 1 week break and everolimus 2.5 mg daily (recommended phase II dose). Due to unexpected hematologic and infectious toxicities, the trial was put on hold, modified, and an additional 9 patients received ribociclib 200 mg and everolimus 2.5 mg daily. The primary end point was progression-free survival. Archived pre-treatment tumor was profiled by next-generation sequencing to evaluate for genomic markers of drug response. Twenty-one patients were treated (median age, 56; range, 24 to 77). The study did not meet the pre-specified criteria to advance to stage two. No patients experienced an objective response. Thirteen patients (62%) experienced stable disease. Median progression-free survival was 7.7 months (95% CI, 2.8 months to not reached). Eleven of the first 12 patients (92%) developed grade 2 or more myelosuppression. Ten patients (84%) experienced treatment interruption and 8 patients (67%) required dose reduction. Genetic testing in archival tumor tissue samples failed to identify a predictive biomarker of disease stabilization. The combination of ribociclib and everolimus had insufficient activity to warrant further investigation in foregut WDNETs.

Comparison of Multimaterial Decomposition Fat Fraction with DECT and Proton Density Fat Fraction with IDEAL IQ MRI for Quantification of Liver Steatosis in a Population Exposed to Chemotherapy.

INTRODUCTION: Oncologic patients who develop chemotherapy-associated liver injury (CALI) secondary to chemotherapy treatment tend to have worse outcomes. Biopsy remains the gold standard for the diagnosis of hepatic steatosis. The purpose of this article is to compare 2 alternatives: Proton-Density-Fat-Fraction (PDFF) MRI and MultiMaterial-Decomposition (MMD) DECT. MATERIALS AND METHODS: 49 consecutive oncologic patients treated with Chemotherapy underwent abdominal DECT and abdominal MRI within 2 weeks of each other. Two radiologists tracked Regions of Interest independently both in the PDFF fat maps and in the MMD DECT fat maps. Non-parametric exact Wilcoxon signed rank test and Cohen's K were used to compare the 2 sequences and to evaluate the agreement. RESULTS: There was no statistically significant difference in the fat fraction measured as a continuous value between PDFF and DECT between 2 readers. Within the same imaging method (PDFF) the degree of agreement based on the k coefficient between reader 1 and reader 2 is 0.88 (p-value < 0.05). Similarly, for single-source DECT(ssDECT) the degree of agreement based on the k coefficient between reader 1 and reader 2 is 0.97 (p-value < 0.05). CONCLUSIONS: The results of this study demonstrate that the hepatic fat fraction of ssDECT with MMD are not significantly different from PDFF. This could be an advantage in an oncological population that undergoes serial CT scans for follow up of chemotherapy response.

Predicting immunotherapy outcomes under therapy in patients with advanced NSCLC using dNLR and its early dynamics.

BACKGROUND: dNLR at the baseline (B), defined by neutrophils/[leucocytes-neutrophils], correlates with immune-checkpoint inhibitor (ICI) outcomes in advanced non-small-cell lung cancer (aNSCLC). However, dNLR is dynamic under therapy and its longitudinal assessment may provide data predicting efficacy. We sought to examine the impact of dNLR dynamics on ICI efficacy and understand its biological significance. PATIENTS AND METHODS: aNSCLC patients receiving ICI at 17 EU/US centres were included [Feb/13-Jun/18]. As chemotherapy-only group was evaluated (NCT02105168). dNLR was determined at (B) and at cycle2 (C2) [dNLR≤3 = low]. B+C2 dNLR were combined in one score: good = low (B+C2), poor = high (B+C2), intermediate = other situations. In 57 patients, we prospectively explored the immunophenotype of circulating neutrophils, particularly the CD15+CD244-CD16lowcells (immature) by flow cytometry. RESULTS: About 1485 patients treatment with ICI were analysed. In ICI-treated patients, high dNLR (B) (~1/3rd) associated with worse progression-free (PFS)/overall survival (OS) (HR 1.56/HR 2.02, P < 0.0001) but not with chemotherapy alone (N = 173). High dNLR at C2 was associated with worse PFS/OS (HR 1.64/HR 2.15, P < 0.0001). When dNLR at both time points were considered together, those with persistently high dNLR (23%) had poor survival (mOS = 5 months (mo)), compared with high dNLR at one time point (22%; mOS = 9.2mo) and persistently low dNLR (55%; mOS = 18.6mo) (P < 0.0001). The dNLR impact remained significant after PD-L1 adjustment. By cytometry, high rate of immature neutrophils (B) (30/57) correlated with poor PFS/OS (P = 0.04; P = 0.0007), with a 12-week death rate of 49%. CONCLUSION: The dNLR (B) and its dynamics (C2) under ICI associate with ICI outcomes in aNSCLC. Persistently high dNLR (B+C2) correlated with early ICI failure. Immature neutrophils may be a key subpopulation on ICI resistance.

Outcomes to first-line pembrolizumab in patients with PD-L1-high (≥50%) non-small cell lung cancer and a poor performance status.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) and a poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) have been excluded from phase III immunotherapy clinical trials. We sought to evaluate clinical outcomes to first-line pembrolizumab in patients with advanced NSCLC, a PD-L1 Tumor Proportion Score (TPS) of ≥50%, and an ECOG PS of 2. METHODS: We performed a multicenter retrospective analysis of patients with metastatic NSCLC and a PD-L1 TPS of ≥50% (negative for genomic alterations in EGFR and ALK) who received treatment with first-line pembrolizumab. Clinical outcomes were compared in patients based on ECOG PS. RESULTS: Among the 234 patients, 83.3% (n=195) had an ECOG PS of 0 or 1, and 16.7% (n=39) had an ECOG PS of 2. The baseline clinicopathological characteristics were balanced between the ECOG PS 0-1 vs 2 groups in terms of age, sex, tobacco use, histology, KRAS mutation status, presence of other potentially targetable driver mutations (BRAF, MET, HER2, RET), presence of brain metastases, and PD-L1 TPS distribution. Compared with patients with an ECOG PS of 0 or 1, patients with an ECOG PS of 2 had a significantly lower objective response rate (43.1% vs 25.6%; p=0.04), a numerically shorter median progression-free survival (6.6 months vs 4.0 months; HR 0.70 (95% CI 0.47 to 1.06); p=0.09), and a significantly shorter median overall survival (20.3 months vs 7.4 months; HR 0.42 (95% CI 0.26 to 0.68); p<0.001). On disease progression, patients with an ECOG PS of 2 were significantly less likely to receive second-line systemic therapy compared with patients with an ECOG PS of 0-1 (65% vs 22.2%, p=0.001). CONCLUSIONS: A subset of patients with NSCLC and an ECOG PS of 2 can respond to first-line pembrolizumab. However, clinical outcomes in this population are often poor and use of second-line systemic therapy is infrequent.

Dual energy computed tomography analysis in cancer patients: What factors affect iodine concentration in contrast enhanced studies?

PURPOSE: The aim of the study is to explore the patient's and scan's parameters that affect the iodine concentration in the abdomen using dual energy computed tomography (DECT) in an oncologic population. METHOD: This is a retrospective study with consecutive patients with different cancers who underwent a single-source DECT (ssDECT) examinations at our institution between years 2015 and 2017. On axial IODINE images, the radiologist manually drew a circular ROI along the inner contour of the aorta. Mean iodine concentration and ROI areas were recorded. Body mass index for every patient was recorded. Descriptive statistics were summarized for iodine concentration and patient/scan characteristics. Linear regression was used to examine associations between iodine concentration in aorta and studied characteristics. Statistical significance was set at a p value < 0.05. RESULTS: The univariate analysis, showed a statistically significant association between iodine concentration within the aorta and the area of ROI (Estimated Coefficient ß: -0.013), the rate of injection (Estimated Coefficient ß: 2.09), the acquisition time (Estimated Coefficient ß: -0.195). In multivariable analysis iodine concentration in the aorta increased with higher rate of injection (4 ml/sec), smaller ROI area and lower BMI. CONCLUSION: Our results showed how iodine concentration is highly dependent on some intrinsic and extrinsic parameters of the examination. These parameters should be taken into account since lower concentration of iodine decrease contrast-to-noise ratio, and in longitudinal follow up studies, they would affect iodine quantitive assessments in cancer patients with frequent chemotherapy-induced variations in BMI and cardiac function.

Lesion-Level Response Dynamics to Programmed Cell Death Protein (PD-1) Blockade.

PURPOSE: Response to programmed cell death protein 1 (PD-1) blockade is often conceptualized as resulting from reinvigoration of tumor-infiltrating lymphocytes. However, recruited antitumor immunity from the periphery may also be an important contributor to response. A detailed assessment of the response dynamics of individual metastasis could provide insight to the systemic and local features that mediate response and resistance to immunotherapy. MATERIALS AND METHODS: Patients with metastatic non-small-cell lung cancer (NSCLC) or mismatch repair deficiency (MMRD) carcinoma treated with PD-1 monotherapy were evaluated independently. Absolute and percent change of each target lesion were quantified at each computed tomography scan using RECIST. Patterns of progression were predefined as systemic or mixed and were correlated with clinical outcomes. RESULTS: A total of 761 individual lesions from 214 patients with NSCLC and 290 lesions from 78 patients with MMRD carcinoma were examined. Individual target lesion responses aligned with best overall response of each patient (85% NSCLC and 93% MMRD lesions responded in patients with partial response/complete response). In responding patients, timing of response was uniform (73% NSCLC and 76% MMRD lesions responded synchronously), and deeper responses were associated with prolonged progression-free survival and overall survival. By contrast, at progression, mixed progression was common (45% of NSCLC and 53% of MMRD) and associated with improved survival compared with those who experienced systemic progression (NSCLC hazard ratio [HR], 0.58; P = .001; MMRD HR, 0.40; P = .07). Organ sites had differential responses, with lymph node and liver metastasis among the most and least responsive, respectively. CONCLUSION: Temporal-spatial patterns of response across individual metastases tend to be uniform, favoring the role of peripheral, clonally directed antitumor immunity as a key mediator of response to PD-1 blockade. In contrast, progression is more heterogeneous, potentially revealing the clinical importance of local features and intertumoral heterogeneity.

11C-Choline Pharmacokinetics in Recurrent Prostate Cancer.

The aim of this study was to investigate the value of pharmacokinetic modeling for quantifying 11C-choline uptake in patients with recurrent prostate cancer. Methods: In total, 194 patients with clinically suspected recurrence of prostate cancer underwent 11C-choline dynamic PET over the pelvic region (0-8 min), followed by a 6-min static acquisition at about 25 min after injection. Regions of interest were drawn over sites of disease identified by a radiologist with experience in nuclear medicine. 11C-choline uptake and pharmacokinetics were evaluated by SUV, graphical analysis (Patlak plot; KiP), and 1- and 2-compartment pharmacokinetic models (K1, K1/k2, k3, k4, and the macro parameter KiC). Twenty-four local recurrences, 65 metastatic lymph nodes, 19 osseous metastases, and 60 inflammatory lymph nodes were included in the analysis, which was subsequently repeated for regions of interest placed over the gluteus maximus muscle and adipose tissue as a control. Results: SUVmean and KiP were 3.60 ± 2.16 and 0.28 ± 0.22 min-1 in lesions, compared with 2.11 ± 1.33 and 0.15 ± 0.10 min-1 in muscle and 0.26 ± 0.07 and 0.02 ± 0.01 min-1 in adipose tissue. According to the Akaike information criterion, the 2-compartment irreversible model was most appropriate in 85% of lesions and resulted in a K1 of 0.79 ± 0.98 min-1 (range, 0.11-7.17 min-1), a K1/k2 of 2.92 ± 3.52 (range, 0.31-20.00), a k3 of 0.36 ± 0.30 min-1 (range, 0.00-1.00 min-1) and a KiC of 0.28 ± 0.22 min-1 (range, 0.00-1.33 min-1). The Spearman ρ between SUV and KiP, between SUV and KiC, and between KiP and KiC was 0.94, 0.91, and 0.97, respectively, and that between SUV and K1, between SUV and K1/k2, and between SUV and k3 was 0.70, 0.44, and 0.33, respectively. Malignant lymph nodes exhibited a higher SUV, KiP, and KiC than benign lymph nodes. Conclusion: Although 11C-choline pharmacokinetic modeling has potential to uncouple the contributions of different processes leading to intracellular entrapment of 11C-choline, the high correlation between SUV and both KiP and KiC supports the use of simpler SUV methods to evaluate changes in 11C-choline uptake and metabolism for treatment monitoring.

CT features of HER2-mutant lung adenocarcinomas.

OBJECTIVES: To describe the radiological phenotype of HER2-mutant lung cancers on CT at presentation. METHODS: Eligible patients with lung adenocarcinomas with HER2 mutations were stage-matched with two control groups (EGFR- and KRAS-mutant groups). Evaluated CT features of the primary tumor included size, location, consistency, contour, presence of pleural tags and pleural retractions. Presence of pleural effusions, lung metastases, adenopathy, chest wall invasion, and were also recorded. Wilcoxon rank-sum and Fisher's exact tests were used to compare continuous and categorical features, respectively. RESULTS: One hundred and fifty-four patients were identified: 50 (33%) harbored HER2 mutations, 56 (36%) harbored KRAS mutations, and 48 (31%) harbored EGFR mutations. Compared with KRAS, HER2 tumors presented as smaller lesions (2.3 cm versus 2.9 cm, p = 0.005 for length; 1.6 cm versus 2.1 cm, p = 0.002 for width) with the presence of pleural tags (74% vs. 52%, p = 0.03), pleural retractions (58% vs. 39%, p = 0.006), ipsilateral hilar (36% vs. 16%, p = 0.03) and scalene/supraclavicular N3 adenopathy (24% vs. 7%, p = 0.03). Compared with EGFR, pleural retractions were more prevalent among the HER2 tumors (58% vs. 37%, p = 0.05). CONCLUSIONS: Lung adenocarcinomas with HER2 gene mutation exhibit an aggressive behavior manifesting by higher incidence of local invasion, compared to KRAS and EGFR mutant controls, and a nodal metastatic spread compared to KRAS-mutant control. This is the first radiogenomics study of HER2 mutations in lung cancer.

Complete metabolic response to therapy of hepatic epithelioid hemangioendothelioma evaluated with 18F-fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography: A CARE case report.

RATIONALE: Hepatic epithelioid hemangioendothelioma (EHE) is a rare malignant vascular tumor of endothelial origin with a highly variable clinical presentation and natural history. Given its vascular origin, new therapies with inhibitors of vascular endothelial growth factor (VEGF) have been introduced in the treatment of these patients and have shown promising results. Few reports have described the role of F-Fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography (F-FDG PET/CT) in the evaluation of this tumor after treatment with anti-angiogenic agents. Our case reports how F-FDG PET-CT scan was critical in the assessment of this tumor after treatment with an anti-angiogenic agent, Pazopanib, demonstrating complete metabolic response. PATIENT CONCERNS: A 30-year-old man with no previous significant medical history presented with pain in the right upper quadrant for over a year. DIAGNOSES: Multiple hepatic masses were found on abdominal ultrasound. Liver biopsy confirmed the diagnosis of epithelioid hemangioendothelioma. F-FDG PET/CT was performed for staging. Multiple FDG-avid hepatic, splenic, and lymph nodes lesions were detected on F-FDG PET/CT. A subsequent spleen biopsy confirmed splenic involvement. Immunohistochemistry was positive for CD31, CD34, and ERG, supporting the diagnosis of epithelioid hemangioendothelioma. INTERVENTIONS: A 1-year cyclophosphamide treatment was provided followed by Pazopanib for 17 months. OUTCOMES: Six years after the first F-FDG PET/CT, F-FDG PET/CT performed for restaging demonstrated complete metabolic response to therapy. Follow-up CT demonstrated no interval changes in size of some of the treated lesions. LESSON: F-FDG PET/CT is useful for baseline assessment and posttreatment follow-up of this rare cancer.

Transient Osteoporosis of the Hip on FDG PET/CT.

Transient osteoporosis of the hip (TOH) is characterized by bone pain, osteopenia, and bone marrow edema in the absence of trauma. We present a 59-year-old man with chronic lymphocytic leukemia who underwent F-FDG PET/CT. F-FDG PET/CT demonstrated mildly FDG-avid lymph nodes consistent for chronic lymphocytic leukemia, as well as FDG-avidity in the right femoral head with corresponding osteopenia, rather than a focal lytic lesion. MR demonstrated bone marrow edema consistent with TOH. TOH is benign and self-limiting. Corresponding imaging may prevent misdiagnosis of benign FDG-avid TOH as other more severe hip processes such as tumors or infection.

Specialized second-opinion radiology review of PET/CT examinations for patients with diffuse large B-cell lymphoma impacts patient care and management.

To identify discrepancies in fludeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) reports generated by general radiologists and subspecialized oncological radiologists for patients with diffuse large B-cell lymphoma (DLBCL), and to assess if such discrepancies impact patient management.Two radiologists retrospectively reviewed 72 PET/CT scans of patients with DLBCL referred to our institutions between 2009 and 2011, and recorded the discrepancies between the outside and second-opinion reports regarding multiple preset criteria using kappa statistic (Κ), including the disease stage. A multidisciplinary staging that considered all patient clinical data, pathology, and follow up radiological scans, was considered as standard of reference. A hemato-oncologist, blinded to the reports' origin, subjectively graded the quality and structure of these reports for each patient to determine if clinical stage and disease activity could be derived accurately from these reports.Agreement was not, or slightly, achieved between the reports regarding the binary and multilevel criteria (Κ < 0-0.2 and weighted Κ = 0.082, respectively). Second-opinion reviews of PET/CT scans were concordant with the multidisciplinary staging in 78% of cases with an almost perfect agreement (Κ = 0.860). A change in staging was demonstrated in 36% of cases. In addition, 68% of second-opinion reports were assigned the highest grades on quality (grades 4 and 5) by the hemato-oncologist, compared with 15% of outside reports, with no noted agreement (weighted Κ = -0.007).Second-opinion review of PET/CT scans by sub-specialized oncological radiologists increases accuracy of initial staging, posttreatment evaluation and also the clinical relevance of the radiology reports.