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If a chest lesion is noted to have been visible on imaging conducted prior to a definitive diagnosis of non-small cell lung cancer, medico-legal action directed against those considered to have missed the initial diagnosis may ensue. Evidence-based approaches to determine the medical impact of the resulting delay are limited. This article reviews strategies for quantifying the medical impact of missed diagnoses and identifies areas for future research. If no nodal or metastatic disease is present at the time of the definitive diagnosis, the potential impact of the delay is sometimes deduced from the differing 5-year overall survival rates of the T status-associated cancer stage at each time point. However, relapse-free survival, specific lung cancer subtype, time from diagnosis and the medical condition of the patient when the evaluation is being made may also have to be considered. In the absence of T-status change, medical impact from any delay is unlikely to be significant, although the effect of changes in patient fitness on outcomes, emotional distress and lost time for the patient's preparation may be argued. When nodal or metastatic involvement is noted at the time of definitive diagnosis, arguments may be made that these did not exist at the time of the missed diagnosis. However, more nuanced calculations considering differences in the risk of spread based on T-stage at each time point would be preferable. Large datasets to inform T to N-status correlations for such calculations already exist, but data to inform T to M-status correlations are limited.

Purpose:Metastasis remains a major hurdle in treating aggressive malignancies such as pancreatic ductal adenocarcinoma (PDAC). Improving response to treatment, therefore, requires a more detailed characterization of the cellular populations involved in controlling metastatic burden.Experimental Design:PDAC patient tissue samples were subjected to RNA sequencing analysis to identify changes in immune infiltration following radiotherapy. Genetically engineered mouse strains in combination with orthotopic tumor models of PDAC were used to characterize disease progression. Flow cytometry was used to analyze tumor infiltrating, circulating, and nodal immune populations.Results:We demonstrate that although radiotherapy increases the infiltration and activation of dendritic cells (DC), it also increases the infiltration of regulatory T cells (Treg) while failing to recruit natural killer (NK) and CD8 T cells in PDAC patient tissue samples. In murine orthotopic tumor models, we show that genetic and pharmacologic depletion of Tregs and NK cells enhances and attenuates response to radiotherapy, respectively. We further demonstrate that targeted inhibition of STAT3 on Tregs results in improved control of local and distant disease progression and enhanced NK-mediated immunosurveillance of metastasis. Moreover, combination treatment of STAT3 antisense oligonucleotide (ASO) and radiotherapy invigorated systemic immune activation and conferred a survival advantage in orthotopic and metastatic tumor models. Finally, we show the response to STAT3 ASO + radiotherapy treatment is dependent on NK and DC subsets.Conclusions:Our results suggest targeting Treg-mediated immunosuppression is a critical step in mediating a response to treatment, and identifying NK cells as not only a prognostic marker of improved survival, but also as an effector population that functions to combat metastasis.

Supplementary Figure from Targeting Treg-Expressed STAT3 Enhances NK-Mediated Surveillance of Metastasis and Improves Therapeutic Response in Pancreatic Adenocarcinoma

Objectives Reporting of United States Medical Licensing Examination Step 1 results will transition from a numerical score to a pass or fail result. We sought an objective analysis to determine changes in the relative importance of resident application attributes when numerical Step 1 results are replaced. Methods A discrete choice experiment was designed to model radiology resident selection and determine the relative weights of various application factors when paired with a numerical or pass or fail Step 1 result. Faculty involved in resident selection at 14 US radiology programs chose between hypothetical pairs of applicant profiles between August and November 2020. A conditional logistic regression model assessed the relative weights of the attributes, and odds ratios (ORs) were calculated. Results There were 212 participants. When a numerical Step 1 score was provided, the most influential attributes were medical school (OR: 2.35, 95% confidence interval [CI]: 2.07-2.67), Black or Hispanic race or ethnicity (OR: 2.04, 95% CI: 1.79-2.38), and Step 1 score (OR: 1.8, 95% CI: 1.69-1.95). When Step 1 was reported as pass, the applicant’s medical school grew in influence (OR: 2.78, 95% CI: 2.42-3.18), and there was a significant increase in influence of Step 2 scores (OR: 1.31, 95% CI: 1.23-1.40 versus OR 1.57, 95% CI: 1.46-1.69). There was little change in the relative influence of race or ethnicity, gender, class rank, or clerkship honors. Discussion When Step 1 reporting transitions to pass or fail, medical school prestige gains outsized influence and Step 2 scores partly fill the gap left by Step 1 examination as a single metric of decisive importance in application decisions.

Current clinical guidelines by both American Association for the Study of Liver Disease and European Association for the Study of the Liver recommend endoscopy in all patients admitted with acute variceal bleeding within 12 hours of admission. Transjugular intrahepatic portosystemic shunt (TIPS) creation may be considered in patients at high risk if hemorrhage cannot be controlled endoscopically. We conducted a cross‐sectional observational study to assess how frequently TIPS is created for acute variceal bleeding in the United States without preceding endoscopy. Adult patients undergoing TIPS creation for acute variceal bleeding in the United States (n = 6,297) were identified in the last 10 available years (2007‐2016) of the National Inpatient Sample. Hierarchical logistic regression was used to examine the relationship between endoscopy nonutilization and hospital characteristics, controlling for patient demographics, income level, insurance type, and disease severity. Of 6,297 discharges following TIPS creation for acute variceal bleeding in the United States, 31% (n = 1,924) did not receive first‐line endoscopy during the same encounter. Rates of “no endoscopy” decreased with increasing population density of the hospital county (nonmicropolitan counties 43%, n = 114; mid‐size metropolitan county 35%, n = 513; and central county with >1 million population 23%, n = 527) but not by hospital teaching status (n = 1,465, 32% teaching vs. n = 430, 26% nonteaching; P = 0.10). Higher disease mortality risk (odds ratio, 0.42; 95% confidence interval, 0.22‐0.80; P = 0.02) was associated with lower odds of noncompliance. Conclusion: One third of all patients undergoing TIPS creation for acute variceal bleeding in the United States do not receive first‐line endoscopy during the same encounter. Patients admitted to urban hospitals are more likely to receive guideline‐concordant care., In this cross‐sectional, population‐based study we examined how often TIPS was created among patients for acute variceal bleeding without use of first‐line endoscopy as recommended by both American Association for the Study of Liver Disease (AASLD) and The European Association for the Study of the Liver (EASL) guidelines. We report endoscopy non‐utilization in nearly a third (n = 1924/6297, 31%) of such encounters nationally. We also found that endoscopy non‐utilization was more prevalent among hospitals in less densely populated counties.

Background Preclinical evidence suggests a link between the renin-angiotensin system and oncogenesis. We aimed to explore the impact of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in head and neck cancer (HNC). Methods Over 5000 patients were identified from the Surveillance, Epidemiology, and End Results-Medicare linked dataset and categorized according to ACEi and ARB and diagnoses of chronic kidney disease (CKD) or hypertension (HTN). Overall survival (OS) and cancer-specific survival (CSS) were compared using Cox multivariable regression (MVA), expressed as hazard ratios (HR) with 95% confidence intervals (95%CI). Results No significant MVA associations for OS or CSS were found for ACEi. Compared to patients with CKD/HTN taking ARB, those with CKD/HTN not taking ARB experienced worse OS (HR 1.28, 95%CI 1.09-1.51, p = 0.003) and CSS (HR 1.23, 95%CI 1.00-1.50, p = 0.050). Conclusions ARB usage is associated with improved OS and CSS among HNC patients with CKD or HTN.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of relapsed/refractory (R/R) B-cell lymphomas, though certain patients do not respond to treatment or relapse afterwards. The purpose of this study is to determine patient variables that are predictive of response to CAR-T therapy.We conducted a retrospective review of 59 R/R B-cell non-Hodgkin lymphoma patients who received anti-CD19 CAR T-cell therapy. Risk factors for progression free survival (PFS) and overall survival (OS) were identified and multivariate logistic regression models for PFS and OS at 1 year were created using stepwise selection. The final multivariate logistic regression models were used to estimate the area under the receiver operating curve (AUROC).At median follow up of 25.6 months, median overall survival was not reached, and median progression free survival was 5.7 months. Stage IV disease (odds ratio (OR) 9.335, P = .025) was identified as a predictive variable for progression at day 365 with an AUC of 0.7922 (P.001). IPI (OR 2.828, P = .014), ALC ≥ 0.50 at collection (OR 0.183, P = .043), CRP ≥ 11 (OR 6.177, P = .019), and tocilizumab administration (OR 0.062, P = .005) as predictors for death at day 365 with an AUC 0.8626 (P.001).Clinical variables identify R/R lymphoma patients who are at risk for progression and poor overall survival after CAR T-cell therapy. IPI, CRP, ALC, and tocilizumab administration may be predictors of survival.

Background: In this population study, we compared head and neck cancer (HNC) prognosis and risk factors in 2 underserved minority groups (Hispanic and Black non-Hispanic patients) with those in other racial/ethnicity groups. Methods: In this SEER-Medicare database study in patients with HNC diagnosed in 2006 through 2015, we evaluated cancer-specific survival (CSS) between different racial/ethnic cohorts as the main outcome. Patient demographics, tumor factors, socioeconomic status, and treatments were analyzed in relation to the primary outcomes between racial/ethnic groups. Results: Black non-Hispanic patients had significantly worse CSS than all other racial/ethnic groups, including Hispanic patients, in unadjusted univariate analysis (Black non-Hispanic patients: hazard ratio, 1.48; 95% CI, 1.33–1.65; Hispanic patients: hazard ratio, 1.12; 95% CI, 0.99–1.28). To investigate the association of several variables with CSS, data were stratified for multivariate analysis using forward Cox regression. This identified socioeconomic status, cancer stage, and receipt of treatment as predictive factors for the survival differences. Black non-Hispanic patients were most likely to present at a later stage (odds ratio, 1.62; 95% CI, 1.38–1.90) and to receive less treatment (odds ratio, 0.67; 95% CI, 0.55–0.81). Unmarried status, high poverty areas, increased emergency department visits, and receipt of healthcare at non-NCI/nonteaching hospitals also significantly impacted stage and treatment. Conclusions: Black non-Hispanic patients have a worse HNC prognosis than patients in all other racial/ethnic groups, including Hispanic patients. Modifiable risk factors include access to nonemergent care and prevention measures, such as tobacco cessation; presence of social support; communication barriers; and access to tertiary centers for appropriate treatment of their cancers.

Background Persistent controversy exists with regard to how and when patients with head and neck cancer should undergo imaging after definitive therapy. The current study was conducted to evaluate whether the type of imaging modality used in posttreatment imaging impacts cancer-specific survival for patients with advanced head and neck squamous cell carcinoma. Methods A retrospective study of National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program-Medicare-linked data in patients with an advanced stage of the 3 most common head and neck malignancies (oral cavity, oropharynx, and larynx) was conducted. Hazard ratios and 95% CIs for cancer-specific survival were estimated for patients diagnosed with any of these cancers between 2006 and 2015. Results Significant improvement with regard to cancer-specific survival was observed among patients with American Joint Committee on Cancer stage III and stage IVA laryngeal cancer who underwent positron emission tomography (PET) and/or computed tomography (CT) imaging during the first 6 months after receipt of definitive treatment (hazard ratio, 0.517; 95% CI, 0.33-0.811) compared with those who underwent CT. There was a trend toward an improvement in cancer-specific survival among patients with oral cavity or oropharyngeal malignancies who underwent PET/CT imaging, but it did not reach statistical significance. Conclusions Compared with CT imaging, posttreatment imaging with PET was associated with improved survival in patients with advanced laryngeal carcinoma.

Purpose: Metastasis remains a major hurdle in treating aggressive malignancies such as pancreatic ductal adenocarcinoma (PDAC). Improving response to treatment, therefore, requires a more detailed characterization of the cellular populations involved in controlling metastatic burden. Experimental Design: PDAC patient tissue samples were subjected to RNA sequencing analysis to identify changes in immune infiltration following radiotherapy. Genetically engineered mouse strains in combination with orthotopic tumor models of PDAC were used to characterize disease progression. Flow cytometry was used to analyze tumor infiltrating, circulating, and nodal immune populations. Results: We demonstrate that although radiotherapy increases the infiltration and activation of dendritic cells (DC), it also increases the infiltration of regulatory T cells (Treg) while failing to recruit natural killer (NK) and CD8 T cells in PDAC patient tissue samples. In murine orthotopic tumor models, we show that genetic and pharmacologic depletion of Tregs and NK cells enhances and attenuates response to radiotherapy, respectively. We further demonstrate that targeted inhibition of STAT3 on Tregs results in improved control of local and distant disease progression and enhanced NK-mediated immunosurveillance of metastasis. Moreover, combination treatment of STAT3 antisense oligonucleotide (ASO) and radiotherapy invigorated systemic immune activation and conferred a survival advantage in orthotopic and metastatic tumor models. Finally, we show the response to STAT3 ASO + radiotherapy treatment is dependent on NK and DC subsets. Conclusions: Our results suggest targeting Treg-mediated immunosuppression is a critical step in mediating a response to treatment, and identifying NK cells as not only a prognostic marker of improved survival, but also as an effector population that functions to combat metastasis.

BACKGROUND The purpose of this study is to evaluate practice patterns and outcomes between intensity-modulated radiation therapy (IMRT) and 3D-conformal radiation (3D-CRT) in early stage glottic cancer. METHODS The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify and compare patient and disease profiles, mortality, and toxicity in patients with T1-2 larynx cancer undergoing definitive radiation (RT). RESULTS A total of 1520 patients underwent definitive radiation with 3D-CRT (n = 1309) or IMRT (n = 211). Non-white race, those with a Charlson Comorbidity Index ≥2, T2 disease, and those treated at community practices were more likely to undergo IMRT. Rates of IMRT increased from 2006 to 2015, while relative rates of 3D-CRT decreased. Two-year CSS was superior with 3D-CRT (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.22-0.65; p

To investigate the use of advanced SPECT/CT quantification in guiding surgical selection of positive sentinel lymph nodes (SLNs) in head and neck melanoma. We retrospectively reviewed data from patients with cutaneous head and neck melanoma who underwent lymphoscintigraphy with SPECT/CT prior to SLN biopsy (SLNB). Quantification of radiotracer uptake from SPECT/CT data was performed using in-house segmentation software. SLNs identified using SPECT/CT were compared to SLNs identified surgically using an intraoperative γ-probe. A radioactivity count threshold using SPECT/CT for detecting a positive SLN was calculated. One hundred and five patients were included. Median number of SLNs detected was 3/patient with SPECT/CT and 2/patient with intraoperative γ-probe. The hottest node identified by SPECT/CT and intraoperative γ-probe were identical in 85% of patients. All 20 histologically positive SLNs were identified by SPECT/CT and γ-probe. On follow-up, all nodal recurrences occurred at lymph node levels with the hottest node identified by SPECT/CT and either the hottest or second hottest node identified by γ-probe during SLNB. Using our data, a SPECT/CT radioactivity count threshold of 20% would eliminate the unnecessary removal of 11% of SPECT/CT identified nodes and 12% of intraoperatively detected nodes. Utilizing SPECT/CT quantification, we propose that a radioactivity count threshold can be developed to help guide the selective removal of lymph nodes in head and neck SLNB. Furthermore, the nodal level containing the hottest node identified by SPECT/CT quantification must be thoroughly investigated for SLNs and undergo careful follow-up and surveillance for recurrence.

BackgroundPrior research demonstrated statistically significant racial disparities related to lung cancer treatment and outcomes. We examined differences in initial imaging and survival between blacks, Hispanics, and non-Hispanic whites.MethodsThe linked Surveillance, Epidemiology, and End Results-Medicare database between 2007 and 2015 was used to compare initial imaging modality for patients with lung cancer. Participants included 28 881 non-Hispanic whites, 3123 black, and 1907 Hispanics, patients age 66 years and older who were enrolled in Medicare fee-for-service and diagnosed with lung cancer. The primary outcome was comparison of positron emission tomography (PET) imaging with computerized tomography (CT) imaging use between groups. A secondary outcome was 12-month cancer-specific survival. Information on stage, treatment, and treatment facility was included in the analysis. Chi-square test and logistic regression were used to evaluate factors associated with imaging use. Kaplan-Meier method and Cox proportional hazards regression were used to calculate adjusted hazard ratios and survival. All statistical tests were two-sided.ResultsAfter adjusting for demographic, community, and facility characteristics, blacks were less likely to undergo PET or CT imaging at diagnosis compared with non-Hispanic whites odds ratio (OR) = 0.54 (95% confidence interval [CI] = 0.50 to 0.59; P ConclusionsBlacks and Hispanics are less likely to undergo guideline-recommended PET with CT imaging at diagnosis of lung cancer, which may partially explain differences in survival. Awareness of this issue will allow for future interventions aimed at reducing this disparity.

Introduction: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of relapsed/refractory (R/R) B-cell lymphomas. Despite this improvement, a subset of patients do not respond to treatment or relapses afterwards. The purpose of this study is to determine patient clinical and radiographic variables that may be predictive of response to CAR-T therapy in order to improve patient selection for CAR-T therapy. Methods: We conducted a single-center retrospective review of all R/R B-cell non-Hodgkin lymphoma patients who received infusion of CAR T-cells from 2017-2020 and had one PET scan post-treatment for response evaluation. Clinicopathological and radiographic parameters were identified a-priori and collected through chart review. PET parameters included standardized uptake value (SUV), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG). For continuous parameters without established cutoffs, variables were dichotomized separately for time to progression and time to death using the Contal and O'Quigley method. Risk factors for progression free survival (PFS) and overall survival (OS) were identified by constructing a univariate Cox proportional hazards regression model. Variables meeting a p-value threshold of 0.10 for PFS or OS were included in stepwise selection to create a final multivariate model for PFS and OS at one year. Variables were retained with a p-value ≤0.05. The same process was also completed to create multivariate logistic regression models for progressive disease and death at one year. The final multivariate logistic regression models were used to estimate the area under the receiver operating curve (AUROC). Results: 64 patients with R/R lymphoma (87% DLBCL) were included in the study. At a median follow up of 23.7 months (95% CI: 16.8 months, 28.8 months), 37 patients (57.8%) progressed and 33 patients (51.6%) remain alive. Median progression free survival (PFS) at 1 year was 9.0 months (95% CI: 3.1 months, not reached) and median overall survival (OS) at 1 year was not reached, though the lower bound of its 95% CI is 11.4 months. Investigating progression at 1 year, the following variables met a p-value threshold of 0.10 in univariate Cox regression models and were therefore included in stepwise selection of the multivariate model for progression: stage (III/IV vs I/II) (odds ratio (OR) 3.132, p=0.0824), extranodal involvement (OR 2.117, p=0.0314), IPI score (OR 1.467, p=0.0125) and tocilizumab administration (OR 0.555, p=0.0932). The final multivariate model identified IPI (OR 1.972, p=0.0022) and tocilizumab administration (OR 0.277, p=0.0095) as predictive variables for PFS at 1 year. Investigating OS at 1 year, the following variables met a p-value threshold of 0.10 in univariate Cox regression models and were therefore included in stepwise selection of the multivariate model for survival: ECOG 2 (OR 4.677, p=0.0757), LDH high (OR 2.401, p=0.0453), CNS involvement (OR 5.030, p=0.0105), IPI (OR 1.720, p=0.0075), Ferritin pre CAR T (continuous) (OR 1.001, p=0.0041), CRS (OR 0.437, p=0.0658), tocilizumab administration (OR 0.363, p=0.0363), TMTV >89 (OR 2.479, p=0.0442), TLG >229 (OR 2.188, p=0.0918), and SUV >18 (OR 2.116, p=0.0906). The final multivariate model identified IPI (OR 1.973, p=0.0082), ferritin (OR 1.001, p=0.0101), and tocilizumab administration (OR 0.216, p=0.0046) as predictive variables for OS at 1 year. The multivariate logistic regression model identified stage IV disease (OR 23.952, p=0.0029) and BMI >24 (OR 0.225, p=0.0472) as predictors for progression at 1 year and IPI (OR 2.607, p=0.0071) and tocilizumab administration (OR 0.108, p=0.0068) as predictors for survival at 1 year. The AUROC for progression and death were 0.815 (p Conclusions: Both clinical and radiographic variables identify R/R lymphoma patients who are at low or high risk for progression and/or poor overall survival after CAR T-cell therapy. IPI, ferritin, BMI, advanced stage, and tocilizumab administration may be predictors of response. These results need validation in larger prospective trials. Figure 1 Figure 1. Disclosures Kamdar: Celgene (BMS): Consultancy; Adaptive Biotechnologies: Consultancy; ADC Therapeutics: Consultancy; AstraZeneca: Consultancy; Genetech: Other; Kite: Consultancy; KaryoPharm: Consultancy; AbbVie: Consultancy; Genentech: Research Funding; TG Therapeutics: Research Funding; SeaGen: Speakers Bureau; Celgene: Other.

Purpose To investigate the magnitude of racial/ethnic differences in hospital mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation for acute variceal bleeding and whether hospital care processes contribute to them. Methods Patients aged ≥18 years undergoing TIPS creation for acute variceal bleeding in the United States (n = 10,331) were identified from 10 years (2007–2016) available in the National Inpatient Sample. Hierarchical logistic regression was used to examine the relationship between patient race and inpatient mortality, controlling for disease severity, treatment utilization, and hospital characteristics. Results A total of 6,350 (62%) patients were White, 1,780 (17%) were Hispanic, and 482 (5%) were Black. A greater proportion of Black patients were admitted to urban teaching hospitals (Black, n = 409 (85%); Hispanic, n = 1,310 (74%); and White, n = 4,802 (76%); P .05) to risk-adjusted mortality. Conclusions Black patients have a 2-fold higher inpatient mortality than non-Black patients following TIPS creation for acute variceal bleeding, possibly related to greater disease severity before the procedure.

To determine whether the recently introduced Bayesian penalized likelihood PET reconstruction (Q.Clear) increases the visual conspicuity and SUVmax of small pulmonary nodules near the PET resolution limit, relative to ordered subset expectation maximization (OS-EM). In this institutional review board-approved and HIPAA-compliant study, 29 FDG PET/CT scans performed on a five-ring GE Discovery IQ were retrospectively selected for pulmonary nodules described in the radiologist’s report as “too small to characterize”, or small lung nodules in patients at high risk for lung cancer. Thirty-two pulmonary nodules were assessed, with mean CT diameter of 8 mm (range 2–18). PET images were reconstructed with OS-EM and Q.Clear with noise penalty strength β values of 150, 250, and 350. Lesion visual conspicuity was scored by three readers on a 3-point scale, and lesion SUVmax and background liver and blood pool SUVmean and SUVstdev were recorded. Comparison was made by linear mixed model with modified Bonferroni post hoc testing; significance cutoff was p

Grading of follicular lymphoma (FL) is important in deciding on a watchful waiting strategy or initiation of chemoimmunotherapy, but accurate determination of grade is complicated by disease heterogeneity and inter-reader variability. Positron emission tomography-computed tomography parameter maximum standardized uptake value (SUVmax) has been studied in differentiating low- versus high-grade FL, but novel parameters total lesion glycolysis (TLG) and total metabolic tumor volume (TMTV) have not been studied and may provide better sensitivity and specificity. SUVmax, TLG, and TMTV were compared in 49 patients with both low-grade and grade 3A FL, and TLG and TMTV had comparable sensitivities and specificities to SUVmax in differentiating low-grade from grade 3A FL. TLG and TMTV are reproducible adjuncts but not replacements for gold-standard biopsy in grading FL. BACKGROUND: Follicular lymphoma (FL) grading, low-grade 1–2 (LG) versus grade 3A (3A), informs management. However, accurate grading is challenging owing to disease heterogeneity and inter-reader variability. The [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) parameter maximum standardized uptake value (SUVmax) has utility in differentiating LG from 3A FL, but the utility of novel parameters total lesion glycolysis (TLG) and total metabolic tumor volume (TMTV) is unknown. PATIENTS AND METHODS: Retrospective review of diagnostic pre-treatment PET-CTs of patients aged > 18 years with FL grades 1–3A from 2009–2017 was performed. PET-CT parameters SUVmax, TLG, and TMTV values were generated using manual (MW) and semi-automated workflows (SW). Poisson regression and receiver operating characteristic curves were used to compare PET-CT parameters between LG and 3A. RESULTS: A total of 49 patients with FL were identified: 38 LG and 11 3A. PET-CT parameters were significantly higher in 3A as compared with LG in both workflows. The cutoff values, sensitivities, and specificities were as follows: SUVmax: 10.4, 64%, and 74% in MW and 11.9, 73%, and 76% in SW; TLG: 543, 82%, and 74% in MW and 371, 73%, and 74% in SW; and TMTV: 141, 73%, and 76% in MW and 93, 64%, and 76% in SW. SUVmax had identical cutoff, sensitivity, and specificity across all 3 SWs, whereas TLG and TMTV had considerable variance across all 3 SWs. CONCLUSIONS: TLG and TMTV are comparable to SUVmax in differentiating LG versus 3A FL. Cutoffs, sensitivities, and specificities varied in MW versus SW. Novel PET-CT parameters serve as reproducible adjuncts but not replacements for biopsy in differentiating grades of FL.

Background The optimal imaging for the staging of oropharyngeal cancer is not well defined. Methods The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database for 2006 through 2011 was used to compare patient characteristics and hospital region by the initial imaging modality used for patients with oropharyngeal cancer. The primary outcome was 3-year cancer-specific survival (CSS). Cox proportional hazards models were adjusted for imaging, age, sex, region, education, race, American Joint Committee on Cancer stage of disease, and treatment, which were examined using backward elimination. The authors also explored how initial imaging use varied by patient characteristics and hospital region. Results A total of 1765 patients underwent initial diagnostic imaging. Of those, approximately 11.4% (202 patients) received computed tomography (CT) alone as their initial imaging modality, 5.2% (91 patients) underwent magnetic resonance imaging (MRI) without positron emission tomography (PET), and 83.3% (1472 patients) had initial imaging that included PET. The overall 3-year CSS rate for the entire population was 63.7%. In the adjusted survival models compared by initial imaging modality, patients who underwent a PET examination were found to have higher survival than those who underwent CT alone or MRI, respectively (hazard ratio, 1.337 [95% CI, 1.001-1.785; P = .0491]; and hazard ratio, 1.748 [95% CI, 1.2-2.545; P = .0036]). Conclusions Among patients with oropharyngeal cancer, initial staging with PET imaging was associated with improved 3-year CSS compared with initial staging with MRI or CT.

Inflammatory changes and residual disease are difficult to distinguish after high dose, definitive radiotherapy of head and neck malignancies. FDG uptake located within a high dose field may more likely represent inflammatory changes, and FDG uptake outside of the radiation field could represent unsuspected and under treated disease. In situ knowledge of the precise radiotherapy fields, therefore, may be useful in distinguishing these etiologies. This study aimed to evaluate the clinical feasibility of rapid integration of radiation treatment field images during follow-up FDG PET/CT imaging. Twenty head and neck cancer patients who underwent radiation therapy were identified. A MIM based workflow was created which fused the radiation treatment CT, including the planning volumes and isodose curves, into the follow-up imaging. Two board certified physicians, blinded to treatment outcome, reviewed the follow-up exams, half with the treatment information and half without. Each exam was scored for recurrent or residual disease, confidence of the read and a qualitative assessment to the overall usefulness of the treatment plan. Interpretation accuracy improved from 80 to 90% with integration of the treatment plan. Similarly, the sensitivity improved from 71% to 86%, while the specificity increased from 85% to 92%. Confidence also increased by 0.7 on a 5 point scale for both readers. Data demonstrate the clinical feasibility of rapidly incorporating radiation treatment dosimetry into follow-up FDG PET/CT exams in patients with head and neck cancer. Preliminary results demonstrated a simple, efficient method which improved accuracy of interpretation and overall reader confidence.

Rationale and Objectives Medical student education in radiology has long been underrepresented in the curriculum despite the increased use of imaging in clinical medicine. Materials and Methods The Beginning to Advanced Radiology Lab, was created with the dedicated purpose of integrating digital technology and interactive teaching methods into the UME curriculum in radiology. Results Results: Development of a novel educational space at the University of Colorado allowed us to identify unforeseen challenges in medical student education while exploring new opportunities Conclusions Conclusion: Curriculum revision in UME radiology education creates both challenges and opportunities and this paper explores these issues in the context of the current paradigm change in medical education.

Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma and requires both bone marrow biopsy and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to correctly stage the disease at diagnosis. However, accurate identification of bone marrow involvement by lymphoma on FDG PET/CT scans has not been previously demonstrated. We hypothesized that a voxel-based analysis of the iliac bones on the FDG PET/CT scan might provide insight into bone marrow involvement.A retrospective cohort study of patients with a diagnosis of MCL who had undergone both single iliac bone marrow biopsy and FDG-PET/CT scan from 1 study site were included in the development phase (n = 10). An additional 12 patients from a second institution were included in the validation phase. Using a semiautomated workflow, a voxel-based data set of FDG uptake within the bilateral iliac bones was captured for each patient. In the development phase, empirical receiver operating characteristic curves for each data set were fit. We then identified the standardized uptake value (SUV) threshold cutpoints at which the sensitivity and specificity were optimized to 100%. In the validation phase, we evaluated the performance of these candidate SUV threshold cutpoints in 15 additional patients from a second institution.We found that 1 cutpoint,38% of voxels with activity 0.95, outperformed all the other candidate cutpoints, correctly classifying all patients except for 1 (overall sensitivity, 100%; specificity, 87.5%).The ability to correctly identify bone marrow involvement using FDG PET/CT-based voxel analysis provides promise as a novel noninvasive method of accurate staging.

Objectives: In oncogene-addicted non-small cell lung cancer (NSCLC), oligoprogressive disease (OPD) can be treated with local ablative therapy (LAT) to prolong benefit from tyrosine kinase inhibitors (TKIs). A comparison of PET/CT vs. CT for the detection of OPD at first extra central nervous system (eCNS) progression was performed to determine which modality was more sensitive for OPD detection. Materials and methods: Patients with metastatic EGFR-MT, ALK + or ROS-1+ NSCLC on a relevant TKI from 2010 to 2016 were identified. Scan methodology at first eCNS progression (index scan) was noted and progression was categorized as OPD (≤ 4 lesions) or non-OPD (> 4 lesions). Results: Of the 67 analyzable patients (EGFR-MT = 37, ALK+ = 28, ROS1+ = 2), OPD was detected in 81.3% (26/32) by PET/CT vs. 68.6% (24/35) by CT (p = 0.363). Of these, 17/26(65.4%) in PET/CT and 5/24(20.8%) in CT group had LAT (p = 0.004). Among patients receiving an alternate modality scan within 6 weeks of the index scan that showed first eCNS progression, 91.7% (11/12) had CT prior to index PET/CT, 75% (6/8) had post-index PET/CT showing further progression, whereas 0% (0/5) had post-index CT showing further progression. Time to progression (TTP), Post-progression TKI benefit (TTP2) and overall survival (OS) were longer in the PET/CT-detected group (p = 0.001, p = 0.032, and p = 0.01, respectively). In both PET/CT (N = 26) and CT-detected (N = 24) OPD subgroups, TTP2 and OS were longer in those that received LAT (65.4% [17/26] and 20.8% [5/24]) versus those that did not, although the difference was not statistically significant. Conclusion: PET/CT demonstrated a non-significant trend to detect more eCNS OPD and a significantly higher rate of OPD suitable for LAT than CT. Peri-progression alternate modality scans were also consistent with PET/CT being more sensitive. A prospective randomized study is required to assess the long-term impact of PET/CT vs CT in oncogene-addicted NSCLC patients on TKI therapy.

A 27-year-old man with stage IV-B Hodgkin's lymphoma status post autologous peripheral stem cell transplant in 2015 with complete response, presented in 2017 with increasing back pain. Restaging contrast enhanced CT demonstrated left brachiocephalic vein occlusion with peripheral nodular high density areas within C7-T2 vertebral bodies with corresponding radiotracer uptake on same day PET/CT. No matching lesion was seen on noncontrast CT. Findings were consistent with pooling of contrast and radiotracer within vertebral venous plexus collaterals at the cervicothoracic junction secondary to brachiocephalic vein occlusion. Repeat PET/CT with contralateral injection of radiotracer and MRI confirmed absence of osseous lymphomatous involvement.

Accurate assessment of disease response is the foundation of therapeutic trails, which is why the Response Evaluation Criteria in Solid Tumors (RECIST) serve as an international standard that investigators can utilize when examining patient outcomes. Nine years after the initial RECIST criteria were released, an update, RECIST 1.1, was published to improve on the initial criteria and address technologic advancements in imaging. Since then, advancements in both standard clinical and trial practices, combined with improvements in our understanding of cancer biology, have resulted in the identification of a number of limitations of the current RECIST 1.1, either in lack of clear guidance with regard to its best application or in potential benefit of capturing imaging-related data beyond standard categorical response details. As several of these situations reflect the consequences of prolonged control of metastatic disease by using targeted therapies, thoracic oncology has generated many of the key scenarios requiring elucidation and/or improvements. This article specifically examines current controversies in the interpretation and/or optimal utilization of RECIST 1.1, focusing on examples from thoracic oncology, and makes proposals, where possible, on how best to address these issues. These situations include addressing central nervous system versus extra–central nervous system response and progression, depth of response, oligoprogression versus polyprogression, continuation of systemic therapy after use of a local ablative therapy, and the impact of fluctuations in measurements bridging partial response and stable disease categories during prolonged therapy.

Mediastinal gray-zone lymphoma is intermediate between classic Hodgkin’s lymphoma and primary mediastinal B-cell lymphoma. Three patients whose disease had become refractory to chemotherapy had impressive responses to PD-1 blockade.

Planar lymphoscintigraphy (PL) has a lower detection rate of sentinel lymph nodes (SLNs) in head and neck melanoma compared with other sites. We assessed situations when single-photon emission computed tomography/computed tomography (SPECT/CT) identified nodes not seen by PL. We also evaluated the impact of SPECT/CT on surgical approach and oncologic outcomes. Patients who underwent SLN biopsy (SLNB) for head and neck melanoma with PL and SPECT/CT between November 2011 and December 2016 were included. Surgeons and radiologists completed a real-time survey inquiring about the utility of SPECT/CT. Patients were divided into two groups: patients with nodal basins identified by both PL and SPECT/CT (‘PL + SPECT/CT’), and patients in whom SPECT/CT identified additional nodal basins not seen on PL (‘SPECT/CT only’). Patient demographics and long-term outcomes including follow-up duration, recurrence, and survival are described. In the PL + SPECT/CT group, 73 (61.9%) patients were included and 45 (38.1%) patients were included in the SPECT/CT-only group. SPECT/CT added 51 basins to those seen on PL, primarily in the supraclavicular region (43.1%). Eighteen patients had positive node(s) in the PL + SPECT/CT group compared with two patients in the SPECT/CT-only group. Surgeons reported that 81% of the time, SPECT/CT influenced the location of incision for SLNB. SPECT/CT influences the location of incision and contributes most to identification of nodes in the supraclavicular region. It also detects additional SLN basins when compared with PL. Further studies are necessary to determine when these additional basins require sampling.

e19541Background: Fluorodeoxyglucose-positron emission tomography with computed tomography (PET-CT) is the preferred staging modality in patients (pts) with follicular lymphoma (FL). PET-CT paramet...

DESCRIPTION OF THE PROBLEM In the era of PACS, imaging has become more efficient and accessible. However, direct consultation and verbal communication between referring physicians and radiologists has dramatically decreased by as much as 82% [1]. As a result, opportunities to develop professional relationships with referring physicians have declined. Radiologists are in a unique position to assume a central role in the inpatient care setting by consulting with medical colleagues, discussing the meaning of imaging reports, and designing approaches to further guide diagnosis and management. Consulting services are gaining attention as an avenue to increase the value of radiologic services [2,3]. To this end, the ACR Imaging 3.0 initiative promotes establishing radiologists as valuable consultants in patient care [4]. Existing studies demonstrate the benefit of clinical-radiologic meetings by highlighting the clinical value of consultations [5-7]. However, no prior study has evaluated the effects on relationships between referring clinicians and radiologists by incorporating a radiologist into clinical rounds. Incorporation of radiology residents into clinical

During the annual 46th annual American Alliance of Academic Chief Residents in Radiology (A(3)CR(2)) meeting in New Orleans, chief residents discussed the role of residents within American College of Radiology 3.0 campaign. Our discussion was directed toward the evolving role of fourth-year radiology residents and how we might improve their training to better prepare them to add value as both leaders and radiologists. The ideas resulting from our Problem Solving session were divided into three categories: clinical presence in the wards and subspecialty clinics; visibility to clinicians and patients; and the education of medical students, residents, and advanced practice clinicians to aid in realizing the long-term goals of Imaging 3.0.

e20683 Background: OPD represents limited extra-central nervous system (eCNS) progression. In oncogene-addicted NSCLC, OPD can be treated with local ablative therapy to prolong TKI control. The impact of PET/CT vs CT to detect OPD at first eCNS progression has not been assessed previously. Methods: Patients with metastatic EGFR-mutant (EGFR-MT), ALK or ROS-1 rearranged (ALK+, ROS-1+) NSCLC with eCNS progression on a relevant TKI (2010-2016) were identified. Scan methodology at first eCNS progression was noted and progression was categorized as OPD using 2 definitions (≤ 2 or ≤ 4 progressing lesions) or non-OPD. Median time-to-progression (MTTP) was calculated from start of TKI to first eCNS progression. Data was analyzed using Chi squared and log rank tests as appropriate using p < 0.05 as significant. Results: Sixty-seven patients (EGFR-MT = 37, ALK+ = 28, ROS-1 = 2) were analyzable. OPD (≤ 2 lesions) occurred in 62.5% (20/32) noted by PET/CT vs. 54.3 % (19/35) by CT (p = 0.496). OPD (≤ 4 lesions) occurred in 84.4 % (27/32) noted by PET/CT vs. 65.7 % (23/35) by CT (p = 0.080). MTTP in PET/CT-detected OPD (≤ 2) (N = 20) was 332.5 days vs. 143 days in CT-detected OPD (N = 19) (p = 0.0092). MTTP in PET/CT-detected non-OPD ( > 2) (N = 12) was 185 days vs. 109 days in CT-detected non-OPD (N = 17) (p = 0.0503). MTTP in PET/CT-detected OPD (≤ 4) (N = 27) was 298 days vs. 143 days in CT-detected OPD (N = 23) (p = 0.0128). MTTP in PET/CT-detected non-OPD ( > 4) (N = 5) was 167 days vs. 104.5 days in CT-detected non-OPD (N = 12) (p = 0.1090). Conclusions: In this non-randomized retrospective study the proportion of OPD (≤ 2 or ≤ 4 progressing lesions) at first eCNS progression did not differ significantly for PET/CT vs. CT. MTTP was significantly longer for PET/CT vs CT detected OPD, but not for non-OPD progression. Potentially longer MTTP in the PET/CT OPD subgroup may reflect preselecting patients with disease difficult to detect by CT (e.g., bone/lymph node) which is more indolent. A prospective randomized study is required to assess the true impact of PET/CT vs CT on detecting OPD in oncogene-addicted NSCLC on TKI therapy.

Sixty-one patients with proven small cell carcinoma of the bronchus were treated by a five-drug pulsed chemotherapy schedule involving cyclophosphamide, vincristine, Adriamycin, methotrexate and prednisolone, given at four-week intervals. The response rate was 60%. All patients also received radiotherapy (4000-5000 rad) to the primary lesion. Survival was identical whether radiotherapy was given first or between the second and third courses of chemotherapy. The survival of responding patients was significantly prolonged as compared both with the non-responders in this series and with a similar group of patients treated only by radiotherapy in this hospital in 1970. The poor results in patients resistant to chemotherapy reflect the fact that 88% of the patients had disseminated disease at the time of diagnosis. The survival of responding patients was not improved over that reported by others as a result of incorporating Adriamycin and prednisolone into the schedule, so there seems no justification for using them in future treatments based on this pattern of chemotherapy. It was possible to identify all responding patients within six weeks of initiating chemotherapy, and a delay of this duration did not affect the efficacy of radiotherapy. Radiotherapy, however, frequently interfered with the subsequent assessment of response to chemotherapy. It therefore seems obligatory to give chemotherapy before radiotherapy in order to determine which patients will benefit from subsequent drug treatment.

The changes in circulating and extravascular lymphocyte pools that followed treatment by extracorporeal irradiation of the blood (ECIB) have been studied by isotopic labeling methods in three patients with chronic lymphocytic leukemia (CLL), each of whom exhibited one of three characteristic patterns of response. The patterns of response, and their interpretations in terms of cell kinetics, were as follows: A rapid, sustained reduction in circulating leukocytes which occurs when extravascular pools are small in relation to the circulating pool. A rapid rise in peripheral count after ECIB due to a transfer of cells from the extravascular depots when extravascular pools are relatively large and cellular exchange is slow. A continuing fall in leukocyte count after ECIB resulting from a differential depletion of proliferating cells when the circulating leukocytes consist both of nonproliferating end cells and of their precursors. These studies have shown that in planning a treatment schedule it is important to determine the nature of the kinetic processes involved.

Transposition of the ovaries to a midline position prior to para-aortic and pelvic irradiation was carried out in eight young women with Hodgkin's disease at the Royal Marsden Hospital between 1965 and 1970. Four of them resumed menstruation—one after 2 years' amenorrhœa. One became pregnant 6 years after irradiation for stage-IIIA Hodgkin's disease and gave birth to a normal child.