Publications

IMPORTANCE: Despite approximately 40% of patients having Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of at least 2 in the real world, most landmark clinical trials that led to the use of pembrolizumab as standard of care in advanced non-small cell lung cancer (NSCLC) excluded this group.

OBJECTIVE: To evaluate whether an ECOG PS score of at least 2 at the start of therapy is associated with progression-free survival (PFS) and overall survival (OS) in advanced NSCLC treated with pembrolizumab monotherapy.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included all consecutive patients with advanced NSCLC who underwent treatment with palliative pembrolizumab monotherapy from February 2016 to October 2019 at a single academic cancer center, with data censoring on January 15, 2020.

EXPOSURES: ECOG PS score at start of therapy, with 0 and 1 indicating fully active or restricted in strenuous activity and scores of 2 and higher indicating increasing disability.

MAIN OUTCOMES AND MEASURES: PFS and OS, measured from initiation of pembrolizumab monotherapy.

RESULTS: Of 74 patients (median [range] age, 68.5 [33-87] years; 36 [48.7%] women; 53 [71.6%] White individuals) with median follow-up of 19.5 (95% CI, 13.4-27.8) months, 45 (60.8%) had an ECOG PS of 0 or 1, while 29 (39.2%) had an ECOG PS of at least 2. There were no significant differences in the baseline characteristics, except in age. Compared with patients with PS scores of 0 or 1, those with PS scores of at least 2 had significantly lower disease control rates (38 [88.4%] vs 15 [53.6%]; P = .002), shorter median PFS (7.9 [95% CI, 4.6-15.4] months vs 2.3 [95% CI, 1.8-4.8] months; P = .004), and shorter median OS (23.2 [14.0 vs 35.7] months vs 4.1 [95% CI, 2.1-6.9] months; P < .001). Among those potentially eligible for subsequent cancer-directed therapy beyond pembrolizumab monotherapy, patients in the group with PS scores of at least 2 were less likely to receive it than those with PS scores of 0 or 1 (2 [8.3%] vs 14 [45.2%]; P = .003). Multivariable adjustment for baseline characteristics confirmed ECOG PS of at least 2 as an independent risk factor for worse PFS (HR, 2.02; 95% CI, 1.09-3.74; P = .03) and worse OS (HR, 2.87; 95% CI, 1.40-5.89; P = .004).

CONCLUSIONS AND RELEVANCE: In this cohort study, having an ECOG PS score of at least 2 was associated with poorer prognosis for treatment of advanced NSCLC with palliative pembrolizumab monotherapy. Further prospective studies are needed to evaluate more objective and consistent measures of functional status to facilitate identification of patients with borderline performance status who may achieve durable clinical benefit from treatment with pembrolizumab monotherapy.

BACKGROUND: Variability of aldosterone concentrations has been described in patients with primary aldosteronism.

METHODS: We performed a retrospective cohort study of 340 patients with primary aldosteronism who underwent adrenal venous sampling (AVS) at a tertiary referral center, 116 of whom also had a peripheral venous aldosterone measured hours before the procedure. AVS was performed by the same interventional radiologist using bilateral, simultaneous sampling, under unstimulated and then stimulated conditions, and each sample was obtained in triplicate. Main outcome measures were: (i) change in day of AVS venous aldosterone from pre-AVS to intra-AVS and (ii) variability of triplicate adrenal venous aldosterone concentrations during AVS.

RESULTS: Within an average duration of 131 minutes, 81% of patients had a decline in circulating aldosterone concentrations (relative decrease of 51% and median decrease of 7.0 ng/dl). More than a quarter (26%) of all patients had an inferior vena cava aldosterone of ≤5 ng/dl at AVS initiation. The mean coefficient of variation of triplicate adrenal aldosterone concentrations was 30% and 39%, in the left and right veins, respectively (corresponding to a percentage difference of 57% and 73%), resulting in lateralization discordance in up to 17% of patients if the lateralization index were calculated using only one unstimulated aldosterone-to-cortisol ratio rather than the average of triplicate measures.

CONCLUSIONS: Circulating aldosterone levels can reach nadirs conventionally considered incompatible with the primary aldosteronism diagnosis, and adrenal venous aldosterone concentrations exhibit acute variability that can confound AVS interpretation. A single venous aldosterone measurement lacks precision and reproducibility in primary aldosteronism.

OBJECTIVES: To determine if superior segmentectomy has equivalent overall (OS), disease-free (DFS), and locoregional-recurrence-free survival (LRFS) to lower lobectomy for early-stage non-small-cell lung cancer (NSCLC) in the superior segment.

METHODS: We retrospectively reviewed all Stage 1 lower lobectomies for superior segment lesions and superior segmentectomies at our hospital from 2000 to 2018. Comparison statistics and Cox hazard modeling were performed to determine differences between groups and attempt to identify risk factors for OS, DFS, and LRFS.

RESULTS: Superior segmentectomy patients, compared with lower lobectomy patients, had more current smokers, worse forced expiratory volume in 1 s percentage, radiologic emphysema scores, clinically and pathologically smaller tumors, and more occurrences of 0 lymph nodes examined. Outcomes for superior segmentectomy compared with lower lobectomy were equivalent for 5-year OS (67.0% vs. 75.1%, p = 0.70), DFS (56.9% vs. 60.4%, p = 0.59), and LRFS (87.9% vs. 91.3%, p = 0.46). Multivariable Cox modeling lacked utility due to no outcome differences.

CONCLUSIONS: In well-selected patients, superior segmentectomies can have equivalent OS, DFS, and LRFS compared with lower lobectomies of superior segment tumors for early stage lung cancer. Further data are needed to provide better risk estimates.

RATIONALE AND OBJECTIVES: COVID-19 has disrupted radiology education and forced a transition from traditional in-person learning to a virtual platform. As a result of hospital and state mandates, our radiology residency program quickly transitioned to a virtual learning platform to continue dissemination of knowledge, maintain resident engagement, and ensure professional development. The goal of this study is to assess the strengths and weaknesses of the virtual learning platform at our institution using resident ratings.

MATERIALS AND METHODS: This institutional IRB-exempt study involved a survey of 17 questions which was electronically distributed to 45 radiology residents using SurveyMonkey. Questions encompassed resident satisfaction with teaching and professional development, scheduling changes, and engagement with the virtual platform. Answers to most questions were submitted on a Likert scale.

RESULTS: A total of 31 of 45 respondents completed the survey (response rate = 69%). Most residents were satisfied with the virtual platform with teaching activities identified as a strength and the incorporation of professional development as a weakness. The most frequent barriers to attending the virtual curriculum were technical difficulties (43%) and childcare (36%). Residents who reported experiencing barriers were less likely to adhere to the virtual curriculum (p = 0.004). Most respondents (81%) reported a desire to maintain elements of the virtual learning practice postpandemic.

CONCLUSION: The majority of residents reported high satisfaction with virtual learning during the COVID-19 pandemic. Teaching activities are a curricular strength. Weaknesses identified include the incorporation of professional development and extrinsic barriers, such as technical difficulties and family obligations, which require further support for trainees.

OBJECTIVES: The aims of the study were to systematically analyze causes for radiation dose outliers in emergency department noncontrast head computed tomographies (CTs), to develop and implement standardized system solutions, and audit program success for an extended period of time.

METHODS: This study was performed in a large, tertiary academic center between January 2015 and September 2017. Four phases of radiation dose data collection with and without prior interventions were performed. Outliers from 5 categories were evaluated for appropriateness in consensus by 2 radiologists and a senior CT technologist.

RESULTS: A total of 275 ± 15 CTs per period were included. Fifty-seven inappropriate scanning parameters were found in 24 (9%) of 254 CTs during the first analysis, 27 in 21 (7%) of 290 CTs during the second, 11 in 10 (4%) of 276 during the third assessment (P = 0.006). After a year without additional intervention, the number remained stable (14 in 11/281 CTs, 4%).

CONCLUSIONS: Combining a dose reporting system, individual case analysis, staff education, and implementation of systemic solutions lead to sustained radiation exposure improvement.

BACKGROUND: Most patients with pineal cysts referred for neurosurgical consultation have no specific symptoms or objective findings except for pineal cyst size to help in management decisions. Our purpose was to assess the relationship between pineal cyst size and aqueductal CSF flow using PC-MRI.

METHODS: Eleven adult patients with pineal cysts (>1 cm) referred for neurosurgical consultations were included. Cyst volume was calculated using 3D T1 images. Phase contrast magnetic resonance imaging (PC-MRI) in axial plane with velocity encoding of 5 cm/sec was used to quantitatively assess CSF flow through the cerebral aqueduct to determine the aqueductal stroke volume, which was then correlated to cyst size using Pearson's correlation. Pineal cysts were grouped by size into small (6/11) and large (5/11) using the median value to compare aqueductal stroke volume using Mann-Whitney test.

RESULTS: Patients were 39±13 years (mean±SD) of age, and 10/11 (91%) were female. There was significant negative correlation between cyst volume and aqueductal stroke volume (r=0.74; P=0.009). Volume of small cysts (4954±2157 mm3) was significantly different compared to large cysts (13,752±3738 mm3; P=0.008). The aqueductal stroke volume of patients harboring large cysts 33±8 μL/cardiac cycle was significantly lower than that of patients with small cysts 96±29 μL/cardiac cycle (P=0.008).

CONCLUSIONS: Aqueductal CSF flow appears to decrease with increasing pineal cyst size. Our preliminary results provide first evidence that even in the absence of objective neurological findings or hydrocephalus; larger pineal cysts already display decreased CSF flow through the cerebral aqueduct.

OBJECTIVE. The purpose of this study was to determine the relationship between background parenchymal enhancement (BPE) on contrast-enhanced mammography (CEM) and breast tissue density, menstrual status, endocrine therapy, and risk factors for breast cancer and also to evaluate interreader agreement on classification of BPE on CEM. MATERIALS AND METHODS. Five subspecialty-trained breast radiologists independently and blindly graded tissue density (with fatty tissue and scattered fibroglandular tissue classified as nondense tissue and with heterogeneously dense and extremely dense classified as dense tissue) and BPE (with minimal or mild BPE categorized as low BPE and moderate or marked BPE categorized as high BPE) on CEM examinations performed from 2014 to 2018. Electronic medical charts were reviewed for information on menstrual status, endocrine therapy, history of breast surgery, and other risk factors for breast cancer. Comparisons were performed using the Kruskal-Wallis test, Mann-Whitney test, and Spearman rank correlation. Interreader agreement was estimated using the Fleiss kappa test. RESULTS. A total of 202 patients (mean [± SD] age, 54 ± 10 years; range, 25-84 years) underwent CEM. Tissue density was categorized as fatty in two patients (1%), scattered fibroglandular in 67 patients (33%), heterogeneously dense in 117 patients (58%), and extremely dense in 16 patients (8%). Among the 202 patients, BPE was minimal in 77 (38%), mild in 80 (40%), moderate in 31 (15%), and marked in 14 (7%). Dense breasts, younger age, premenopausal status, no history of endocrine therapy, and no history of breast cancer were significantly associated with high BPE. Among premenopausal patients, no association was found between BPE and time from last menstrual period to CEM. Overall interreader agreement on BPE was moderate (κ = 0.41; 95% CI, 0.40-0.42). Interreader agreement on tissue density was substantial (κ = 0.67; 95% CI, 0.66-0.69). CONCLUSION. Women with dense breasts, premenopausal status, and younger age are more likely to have greater BPE. Targeting CEM to the last menstrual period is not indicated.

Testosterone therapy (TT) is administered to enhance masculinization in transgender individuals. The long-term effect of exogenous testosterone on breast tissues remains unclear. Our study evaluated the modulation of breast morphology by TT in transgender individuals with special attention to duration of TT. We reviewed 447 breast surgical specimens from gender affirming chest-contouring surgery, and compared histopathological findings including degree of lobular atrophy, and atypical and non-atypical proliferations between subjects who did (n = 367) and did not (n = 79) receive TT. TT for one patient was unknown. TT for >12 months was associated with seven histopathological features. Longer duration of TT was significantly associated with higher degrees of lobular atrophy (p < 0.001). This relationship remained significant after accounting for age at surgery, ethnicity, body mass index, and presurgical oophorectomy (adjusted p < 0.001). Four types of lesions were more likely to be absent in breast tissues exposed to longer durations of TT: cysts (median = 16.2 months; p < 0.01; adjusted p = 0.01), fibroadenoma (median = 14.8 months; p = 0.02; adjusted p = 0.07), pseudoangiomatous stromal hyperplasia (median = 17.0 months; p < 0.001; adjusted p < 0.001), and papillomas (median = 14.7 months; p = 0.04; adjusted p = 0.20). Columnar cell change and mild inflammation were also less likely to occur in subjects receiving TT (p < 0.05), but were not linked to the duration of TT. Atypia and ductal carcinoma in situ were detected in 11 subjects (2.5%) all of whom received TT ranging from 10.1 to 64.1 months. The incidental findings of high-risk lesions and carcinoma as well as the risk of cancer in residual breast tissue after chest-contouring surgery warrant the consideration of culturally sensitive routine breast cancer screening protocols for transgender men and masculine-centered gender nonconforming individuals. Long-term follow-up studies and molecular investigations are needed to understand the breast cancer risk of transgender individuals who receive TT.

BACKGROUND: Patient genetic polymorphism is associated with Crohn's clinical behavior; however, its association with magnetic resonance enterography (MRE) imaging appearance is not known.

PURPOSE: To analyze a set of known Crohn's disease (CD)-related single nucleotide polymorphisms for associations with MRE imaging phenotype and frequency of imaging.

STUDY TYPE: Retrospective.

POPULATION: 54 patients (mean age 40 years; 32 females and 22 males) with established CD from 2009 to 2016 who underwent baseline MRE and genetic testing for the presence of 168 single nucleotide polymorphisms (SNPs) potentially associated with inflammatory bowel disease.

FIELD STRENGTH/SEQUENCE: 1.5T or 3T clinical scanners, standard MRE clinical pulse sequences, including T2 -weighted single-shot fast spin echo, balanced steady-state free precession, T2 -weighted fast spin echo fat-suppressed, and T1 -weighted fat-suppressed pre- and postcontrast imaging.

ASSESSMENT: Three readers (all body imaging fellowship-trained radiologists) independently evaluated all imaging for the presence or absence of active disease and penetrating complications. Date of onset and frequency of endoscopies and cross-sectional imaging (CSI) were recorded. Disease behavior and distribution were categorized according to the Vienna and Montreal classifications, respectively.

STATISTICAL TESTS: Student's t-test and Fisher's exact test were used to assess significance of continuous and categorical variables, respectively. A hidden Markov model statistical knockoff approach was also applied for the analysis of genetic-imaging associations, with corrected P < 0.05 considered significant.

RESULTS: MRE demonstrated active bowel inflammation in 42 (78%) patients, strictures in 13 (28%), and fistulae in 13 (28%). The SNP rs1292053 (RBS6KB1) was highly associated with small bowel inflammation and luminal narrowing, with observed frequencies of association 0.66 and 0.39, respectively (P = 0.001). rs6062504 (Decoy receptor 3) was associated with lower age of onset (P = 0.012), higher proportion of early disease onset patients (P = 0.012), and higher average number of CSI/year (P = 0.014).

DATA CONCLUSION: This study demonstrated significant associations between CD genotype and MRE phenotype and frequency of cross-sectional imaging.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.