Diagnostic Performance of Point-of-Care Apparent Diffusion Coefficient Measures to Reduce Biopsy in Breast Lesions at MRI: Clinical Validation.

Background The Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group multicenter A6702 trial identified an optimal apparent diffusion coefficient (ADC) cutoff to potentially reduce biopsies by 21% without affecting sensitivity. Whether this performance can be achieved in clinical settings has not yet been established. Purpose To validate the performance of point-of-care ADC measurements with the A6702 trial ADC cutoff for reducing unnecessary biopsies in lesions detected at breast MRI. Materials and Methods Consecutive breast MRI examinations performed from May 2015 to January 2019 at a single medical center and showing biopsy-confirmed Breast Imaging Reporting and Data System category 4 or 5 lesions, without ipsilateral cancer, were identified. Point-of-care lesion ADC measurements collected at clinical interpretation were retrospectively evaluated. MRI examinations included axial T2-weighted, diffusion-weighted, and dynamic contrast-enhanced sequences. Sensitivity and biopsy reduction rates were calculated by applying the A6702 optimal (ADC, 1.53 × 10-3 mm2/sec) and alternate conservative (1.68 × 10-3 mm2/sec) cutoffs. Lesion pathologic outcomes were the reference standard. To assess reproducibility, one radiologist repeated ADC measurements, and agreement was summarized using the intraclass correlation coefficient. Results A total of 240 lesions in 201 women (mean age, 49 years ± 13 [SD]) with pathologic outcomes (63 malignant and 177 benign) were included. Applying the optimal ADC cutoff produced an overall biopsy reduction rate of 15.8% (38 of 240 lesions [95% CI: 11.2, 20.9]), with a sensitivity of 92.1% (58 of 63 lesions [95% CI: 82.4, 97.4]; sensitivity was 97.2% [35 of 36 lesions] [95% CI: 82.7, 99.6] for invasive cancers). Results were similar for screening versus diagnostic examinations (P = .92 and .40, respectively). Sensitivity was higher for masses than for nonmass enhancements (NMEs) (100% vs 85.3%; P = .009). Applying the conservative ADC cutoff achieved a sensitivity of 95.2% (60 of 63 lesions [95% CI: 86.7, 99.0]), with a biopsy reduction rate of 10.4% (25 of 240 lesions [95% CI: 6.7, 14.5]). Repeated single-reader measurements showed good agreement with clinical ADCs (intraclass correlation coefficient, 0.72 [95% CI: 0.58, 0.81]). Conclusion This study validated the clinical use of ADC cutoffs to reduce MRI-prompted biopsies by up to 16%, with a suggested tradeoff of lowered sensitivity for in situ and microinvasive disease manifesting as NME. Clinical trial registration no. NCT02022579 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Honda and Iima in this issue.

Development and psychometric properties of the Functional Assessment of Cancer Therapy-Cutaneous T-Cell Lymphoma (FACT-CTCL).

BACKGROUND: Patients with Mycosis Fungoides (MF)/Sézary Syndrome (SS) can experience impacted health-related quality of life (HRQoL). OBJECTIVES: To validate the CTCL-S, a novel subscale of the Functional Assessment of Cancer Therapy - General (FACT-G), in patients with MF/SS. METHODS: Qualitative interviews were conducted with expert clinicians and MF/SS patients. Thematic analysis identified the most common concerns, and 19 items were selected.MF/SS patients were recruited from a single center. FACT-G, CTCL-S (collectively "FACT-CTCL"), Skindex29, and Visual Analogue Scale-Pruritis (VAS itch) were administered. A subset repeated FACT-CTCL and VAS itch after ≈2 weeks. Patient demographics and clinical characteristics were obtained via review of the electronic medical record.Psychometric properties were assessed. Internal consistency was estimated using Cronbach's alpha (α). Convergent and discriminant validity were assessed by comparing CTCL-S to disease stage, age, VAS itch, FACT-G, and SkinDex29. Exploratory factor analysis (EFA) was used to preliminarily assess CTCL-S dimensionality. Test-retest repeatability was summarized using intraclass correlation coefficient (ICC), within-subject standard deviation (wSD), and within-subject coefficient of variation. RESULTS: Seventy-two patients completed the initial survey, and 35 repeated the FACT-CTCL and VAS itch after ≈2 weeks. Two-thirds were male, most were white (78%). The majority (85%) had MF, 15% SS, and 75% early (stage IA-IIA) and 25% advanced (≥ stage IIB) disease. Preliminary EFA found a single predominant factor, supporting a hypothesis of unidimensionality of the CTCL-S. Internal consistency of the CTCL-S was high (α: 0.95 [95% CI: 0.93-0.96]). There was no significant change in CTCL-S average test-retest scores (ICC of 0.93 (p = 0.63)). CTCL-S was significantly lower in advanced vs early stage disease (median[IQR]: 34[26, 48] vs. 59[44, 68], p < 0.001) and strongly correlated with VAS itch (Spearman's r (rs): -0.70, 95% CI: -0.81, -0.55), FACT-G (rs: 0.77, 95% CI: 0.65, 0.85), and Skindex29 (rs: -0.90, 95% CI: -0.94, -0.84), supporting convergent validity. CTCL-S scores had little correlation with age (rs: 0.19, 95% CI: -0.05, 0.41, p = 0.12), supporting discriminant validity. CONCLUSIONS: The FACT-CTCL is a disease specific instrument for assessing HRQoL with high reproducibility and good performance in a cohort of patients with MF/SS.

Estimating infants' language exposure: A comparison of random and volume sampling from daylong recordings collected in a bilingual community.

In North America, the characteristics of a child's language environment predict language outcomes. For example, differences in bilingual language exposure, exposure to electronic media, and exposure to child-directed speech (CDS) relate to children's language growth. Recently, these predictors have been studied through the use of daylong recordings, followed by manual annotation of audio samples selected from these recordings. Using a dataset of daylong recordings collected from bilingually raised infants in the United States as an example, we ask whether two of the most commonly used sampling methods, random sampling and sampling based on high adult speech, differ from each other with regard to estimating the frequencies of specific language behaviors. Daylong recordings from 37 Spanish-English speaking families with infants between 4 and 22 months of age were analyzed. From each child's recording, samples were extracted in two ways (at random/based on high adult speech) and then annotated for Language (Spanish/English/Mixed), CDS, Electronic Media, Social Context, Turn-Taking, and Infant Babbling. Correlation and agreement analyses were performed, in addition to paired sample t-tests, to assess how the choice of one or the other sampling method may affect the estimates. For most behaviors studied, correlation and agreement between the two sampling methods was high (Pearson r values between 0.79 and 0.99 for 16 of 17 measures; Intraclass Correlation Coefficient values between 0.78 and 0.99 for 13 of 17 measures). However, interesting between-sample differences also emerged: the degree of language mixing, the amount of CDS, and the number of conversational turns were all significantly higher when sampling was performed based on high adult speech compared to random sampling. By contrast, the presence of electronic media and one-on-one social contexts was higher when sampling was performed at random. We discuss advantages of choosing one sampling technique over the other, depending on the research question and variables at hand.

An alternating-intervention pilot trial on the impact of an informational handout on patient-reported outcomes and follow-up after lung cancer screening.

INTRODUCTION: Lung cancer screening (LCS) can reduce lung cancer mortality; however, poor understanding of results may impact patient experience and follow-up. We sought to determine whether an informational handout accompanying LCS results can improve patient-reported outcomes and adherence to follow-up. STUDY DESIGN: This was a prospective alternating intervention pilot trial of a handout to accompany LCS results delivery. SETTING/PARTICIPANTS: Patients undergoing LCS in a multisite program over a 6-month period received a mailing containing either: 1) a standardized form letter of LCS results (control) or 2) the LCS results letter and the handout (intervention). INTERVENTION: A two-sided informational handout on commonly asked questions after LCS created through iterative mixed-methods evaluation with both LCS patients and providers. OUTCOME MEASURES: The primary outcomes of 1)patient understanding of LCS results, 2)correct identification of next steps in screening, and 3)patient distress were measured through survey. Adherence to recommended follow-up after LCS was determined through chart review. Outcomes were compared between the intervention and control group using generalized estimating equations. RESULTS: 389 patients were eligible and enrolled with survey responses from 230 participants (59% response rate). We found no differences in understanding of results, identification of next steps in follow-up or distress but did find higher levels of knowledge and understanding on questions assessing individual components of LCS in the intervention group. Follow-up adherence was overall similar between the two arms, though was higher in the intervention group among those with positive findings (p = 0.007). CONCLUSIONS: There were no differences in self-reported outcomes between the groups or overall follow-up adherence. Those receiving the intervention did report greater understanding and knowledge of key LCS components, and those with positive results had a higher rate of follow-up. This may represent a feasible component of a multi-level intervention to address knowledge and follow-up for LCS. TRIAL REGISTRATION: ClinicalTrials.gov NCT05265897.

Spinal infection: Assessing comorbidities and costs to inform patient management and resource use strategies.

Background: Spinal Infection (SI) is associated with various comorbidities. The interaction of these comorbidities and their impact on costs and complexity of care has not been fully assessed. Methods: This is a retrospective cohort study of SI patients in an urban hospital system to characterize comorbidities and outcomes in adult patients with SI. Adult patients in our hospital system who were hospitalized with an initial diagnosis of SI between July 1, 2017 and June 30, 2019 were included. Outcomes measures included length of stay (LOS) of the index hospitalization for SI, charges and payments for the index hospitalization, and hospital readmissions within one year after discharge from the index hospitalization. Data was obtained by querying our Electronic Data Warehouse (EDW) using ICD-10-CM and CPT procedure codes. Spearman's correlation was used to summarize the relationships between LOS, charges, and payments. Multivariable linear regression was used to evaluate associations of demographics, comorbidities, and other factors with LOS. Multivariable Cox regression was used to evaluate associations of demographics, comorbidities, and other factors with hospital readmissions. Results: 403 patients with a first diagnosis of SI were identified. The average number of comorbidities per patient was 1.3. 294 (73%) had at least 1 medical comorbidity, and 54 (13%) had 3 or more comorbidities. The most common medical comorbidities were diabetes mellitus (26%), intravenous drug use (IVDU, 26%), and malnutrition (20%). 112 patients (28%) had a surgical site infection (SSI). DM (p<.001) and SSI (p=.016) were more common among older patients while IVDU was more common among younger patients (p<.001). Median LOS was 12 days. A larger number of medical comorbidities was associated with a longer LOS (p<.001) while the presence of a SSI was associated with a shorter LOS (p=.007) after multivariable adjustment. LOS was positively correlated with both charges (r=0.83) and payments (r=0.61). Among 389 patients discharged after the index hospitalization, 36% had a readmission within 1 year. The rate of readmission was twice as high for patients with three or more comorbidities than patients with zero comorbidities (hazard ratio: 1.95, p=.017). Conclusions: Patients with SI often have multiple comorbidities, and the specific type of comorbidity is associated with the patient's age. The presence of multiple comorbidities correlates with initial LOS, cost of care, and readmission rate. Readmission in the first year post-discharge is high.

Lack of Clinically Significant Relationships of Age or Body Mass Index with Merkel Cell Carcinoma Immunotherapy Outcomes.

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with a high risk of metastasis. The development of anti-PD-1/PD-L1 immunotherapy has improved outcomes for advanced MCC, yet about 50% of such patients do not achieve durable responses. This study analyzed the effects of age and body mass index (BMI) on immunotherapy response in 183 advanced MCC patients from a single-center longitudinal database. Using Fine-Gray or Cox regression models, treatment response, progression-free survival (PFS), MCC-specific survival, and overall survival (OS) were evaluated. Age showed a significant non-linear relationship with treatment response (p = 0.04), with patients much older or younger than 70 years less likely to respond. However, age was not significantly associated with PFS (p = 0.21), MCC-specific survival (p = 0.72), or OS (p = 0.36). Similarly, BMI was not significantly correlated with treatment response (p = 0.41), PFS (p = 0.52), MCC-specific survival (p = 0.78), or OS (p = 0.71). Unlike previous studies suggesting that obesity and advanced age improve outcomes in other cancers, these associations were not observed in MCC. These findings suggest that age and BMI should not influence eligibility for immunotherapy in MCC patients, emphasizing the importance of unbiased patient selection for this treatment.

GWO+RuleFit: rule-based explainable machine-learning combined with heuristics to predict mid-treatment FDG PET response to chemoradiation for locally advanced non-small cell lung cancer.

Objective.Vital rules learned from fluorodeoxyglucose positron emission tomography (FDG-PET) radiomics of tumor subregional response can provide clinical decision support for precise treatment adaptation. We combined a rule-based machine learning (ML) model (RuleFit) with a heuristic algorithm (gray wolf optimizer, GWO) for mid-chemoradiation FDG-PET response prediction in patients with locally advanced non-small cell lung cancer.Approach.Tumors subregions were identified using K-means clustering. GWO+RuleFit consists of three main parts: (i) a random forest is constructed based on conventional features or radiomic features extracted from tumor regions or subregions in FDG-PET images, from which the initial rules are generated; (ii) GWO is used for iterative rule selection; (iii) the selected rules are fit to a linear model to make predictions about the target variable. Two target variables were considered: a binary response measure (ΔSUVmean ⩾ 20% decline) for classification and a continuous response measure (ΔSUVmean) for regression. GWO+RuleFit was benchmarked against common ML algorithms and RuleFit, with leave-one-out cross-validated performance evaluated by the area under the receiver operating characteristic curve (AUC) in classification and root-mean-square error (RMSE) in regression.Main results.GWO+RuleFit selected 15 rules from the radiomic feature dataset of 23 patients. For treatment response classification, GWO+RuleFit attained numerically better cross-validated performance than RuleFit across tumor regions and sets of features (AUC: 0.58-0.86 vs. 0.52-0.78,p= 0.170-0.925). GWO+Rulefit also had the best or second-best performance numerically compared to all other algorithms for all conditions. For treatment response regression prediction, GWO+RuleFit (RMSE: 0.162-0.192) performed better numerically for low-dimensional models (p= 0.097-0.614) and significantly better for high-dimensional models across all tumor regions except one (RMSE: 0.189-0.219,p< 0.004).Significance. The GWO+RuleFit selected rules were interpretable, highlighting distinct radiomic phenotypes that modulated treatment response. GWO+Rulefit achieved parsimonious models while maintaining utility for treatment response prediction, which can aid clinical decisions for patient risk stratification, treatment selection, and biologically driven adaptation. Clinical trial: NCT02773238.

Repeatability of 18F-FDG uptake in metastatic bone lesions of breast cancer patients and implications for accrual to clinical trials.

BACKGROUND: Standard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients with bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases.In this study, nine patients with 38 bone lesions were imaged with 18F-FDG in the same calibrated scanner twice within 14 days. Tumor uptake was quantified as the maximum tumor voxel normalized by dose and body weight (SUVmax) and the mean of a 1-cc maximal uptake volume normalized by dose and lean-body-mass (SULpeak). The asymmetric repeatability coefficients with confidence intervals of SUVmax and SULpeak were used to determine limits of 18F-FDG uptake variability. A second cohort of 28 breast cancer patients with bone-dominant metastases that had 146 metastatic bone lesions was imaged with 18F-FDG before and after standard-of-care therapy for response assessment. RESULTS: The mean relative difference of SUVmax in 38 bone tumors of the first cohort was 4.3%. The upper and lower asymmetric limits of the repeatability coefficient were 19.4% and -16.3%, respectively. The 18F-FDG repeatability coefficient confidence intervals resulted in the following patient stratification for the second patient cohort: 11-progressive disease, 5-stable disease, 7-partial response, and 1-complete response with three inevaluable patients. The asymmetric repeatability coefficients response criteria changed the status of 3 patients compared to standard the standard Positron Emission Tomography Response Criteria in Solid Tumors of ±30% SULpeak. CONCLUSIONS: In evaluating bone tumor response for breast cancer patients with bone-dominant metastases using 18F-FDG uptake, the repeatability coefficients from test-retest studies show that reductions of more than 17% and increases of more than 20% are unlikely to be due to measurement variability. Serial 18F-FDG imaging in clinical trials investigating bone lesions from these patients, such as the ECOG-ACRIN EA1183 trial, benefit from confidence limits that allow interpretation of response.

Practice Patterns of Spatially Fractionated Radiation Therapy: A Clinical Practice Survey.

Purpose: Spatially fractionated radiation therapy (SFRT) is increasingly used for bulky advanced tumors, but specifics of clinical SFRT practice remain elusive. This study aimed to determine practice patterns of GRID and Lattice radiation therapy (LRT)-based SFRT. Methods and Materials: A survey was designed to identify radiation oncologists' practice patterns of patient selection for SFRT, dosing/planning, dosimetric parameter use, SFRT platforms/techniques, combinations of SFRT with conventional external beam radiation therapy (cERT) and multimodality therapies, and physicists' technical implementation, delivery, and quality procedures. Data were summarized using descriptive statistics. Group comparisons were analyzed with permutation tests. Results: The majority of practicing radiation oncologists (United States, 100%; global, 72.7%) considered SFRT an accepted standard-of-care radiation therapy option for bulky/advanced tumors. Treatment of metastases/recurrences and nonmetastatic primary tumors, predominantly head and neck, lung cancer and sarcoma, was commonly practiced. In palliative SFRT, regimens of 15 to 18 Gy/1 fraction predominated (51.3%), and in curative-intent treatment of nonmetastatic tumors, 15 Gy/1 fraction (28.0%) and fractionated SFRT (24.0%) were most common. SFRT was combined with cERT commonly but not always in palliative (78.6%) and curative-intent (85.7%) treatment. SFRT-cERT time sequencing and cERT dose adjustments were variable. In curative-intent treatment, concurrent chemotherapy and immunotherapy were found acceptable by 54.5% and 28.6%, respectively. Use of SFRT dosimetric parameters was highly variable and differed between GRID and LRT. SFRT heterogeneity dosimetric parameters were more commonly used (P = .008) and more commonly thought to influence local control (peak dose, P = .008) in LRT than in GRID therapy. Conclusions: SFRT has already evolved as a clinical practice pattern for advanced/bulky tumors. Major treatment approaches are consistent and follow the literature, but SFRT-cERT combination/sequencing and clinical utilization of dosimetric parameters are variable. These areas may benefit from targeted education and standardization, and knowledge gaps may be filled by incorporating identified inconsistencies into future clinical research.

Repeatability of 18F-FDG uptake in metastatic bone lesions of breast cancer patients and implications for accrual to clinical trials.

BACKGROUND: Standard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients that have bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases. METHODS: For this study, nine patients with 38 bone lesions were imaged with 18F-FDG in the same calibrated scanner twice within 14 days. Tumor uptake was quantified by the most commonly used PET parameter, the maximum tumor voxel normalized by dose and body weight (SUVmax) and also by the mean of a 1-cc maximal uptake volume normalized by dose and lean-body-mass (SULpeak). The asymmetric repeatability coefficients with confidence intervals for SUVmax and SULpeak were used to determine the limits of 18F-FDG uptake variability. A second cohort of 28 breast cancer patients with bone-dominant metastases that had 146 metastatic bone lesions was imaged with 18F-FDG before and after standard-of-care therapy for response assessment. RESULTS: The mean relative difference of SUVmax and SULpeak in 38 bone tumors of the first cohort were 4.3% and 6.7%. The upper and lower asymmetric limits of the repeatability coefficient were 19.4% and - 16.3% for SUVmax, and 21.2% and - 17.5% for SULpeak. 18F-FDG repeatability coefficient confidence intervals resulted in the following patient stratification using SULpeak for the second patient cohort: 11-progressive disease, 5-stable disease, 7-partial response, and 1-complete response with three inevaluable patients. The asymmetric repeatability coefficients response criteria for SULpeak changed the status of 3 patients compared to the standard Positron Emission Tomography Response Criteria in Solid Tumors of ± 30% SULpeak. CONCLUSION: In evaluating bone tumor response for breast cancer patients with bone-dominant metastases using 18F-FDG SUVmax, the repeatability coefficients from test-retest studies show that reductions of more than 17% and increases of more than 20% are unlikely to be due to measurement variability. Serial 18F-FDG imaging in clinical trials investigating bone lesions in these patients, such as the ECOG-ACRIN EA1183 trial, benefit from confidence limits that allow interpretation of response.

Pathophysiology of carotid atherosclerosis: Calcification, intraplaque haemorrhage and pulse pressure as key players.

PURPOSE: Intraplaque haemorrhage (IPH) is a well-known risk factor for faster plaque progression (volume increase); however, its etiology is unclear. We aimed at determining what other local plaque- and systemic factors contribute to plaque progression and to the development and progression of IPH. METHODS: We examined 98 asymptomatic participants with carotid plaque using serial multi-contrast magnetic resonance imaging. We measured the percent of wall volume (%WV=100 x [wall volume] / [total vessel volume]) and measured IPH and calcification volumes. We used generalized estimating equations-based regression to analyze predictors of %WV change and new IPH while accounting for covariates (sex, age and statin use), and multiple non-independent observations per participant. RESULTS: Total follow-up was 1.8 ± 0.8 years on average. The presence of IPH (ß: 0.6 %/y, p = 0.033) and calcification (ß: 1.2 %/y, p = 0.028) were each associated with faster plaque progression. New IPH, detected on a subsequent scan in 4 % of arteries that did not initially have IPH, was associated with larger calcification (odds ratio [OR]: 2.6 per 1-SD increase, p = 0.038) and higher pulse pressure (OR: 2.3 per 1-SD increase, p = 0.016). Larger calcification was associated with greater increases in pulse pressure (ß: 1.4 mm Hg/y per 1-SD increase, p = 0.040). CONCLUSIONS: IPH and calcification are each independently associated with faster plaque progression. The association of carotid calcification to increased pulse pressure and new IPH development suggests a possible mechanism by which calcification drives IPH development and plaque progression.

Postoperative Radiation Therapy Is Indicated for "Low-Risk" Pathologic Stage I Merkel Cell Carcinoma of the Head and Neck Region but Not for Other Locations.

Purpose: The role of postoperative radiation therapy (PORT) in early stage Merkel cell carcinoma (MCC) is controversial. We analyzed the role of PORT in preventing local recurrences (LR) among patients with low-risk, pathologic stage I MCC based on the location of the primary tumors: head/neck (HN) versus non-HN sites. Methods and Materials: One hundred forty-seven patients with MCC were identified that had "low risk" disease (pathologic T1 primary tumor, negative microscopic margins, negative pathologic node status, no immunosuppression or prior systemic therapy). LR was defined as tumor recurrence within 2 cm of the primary surgical bed, and its frequency was estimated with the cumulative incidence method. Results: Seventy-nine patients received PORT (30 HN, 49 non-HN) with a median dose of 50 Gy (range, 8-64 Gy) and 68 patients were treated with surgery alone (30 HN, 38 non-HN). Overall, PORT was associated with a decreased risk of LR (5-year rate: 0% vs 9.5%; P = .004) with 6 LRs observed in the surgery alone group. Although the addition of PORT significantly reduced LR rates among patients with HN MCC (0% vs. 21%; P = .034), no LRs were observed in patients with non-HN MCC managed with surgery alone. There was no significant difference in MCC-specific survival comparing HN versus non-HN groups, with or without PORT. Conclusions: For low-risk, pathologic stage I MCC of the extremities and trunk, excellent local control rates were achieved with surgery, and PORT is not indicated. However, PORT was associated with a significant reduction in LRs among low-risk MCC of the HN.

Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications.

PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence. METHODS: Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed. RESULTS: ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20]). CONCLUSION: ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials.

Women's Experience With Screening Mammography During the COVID-19 Pandemic: A Multi-Institutional Prospective Survey Study.

OBJECTIVE: Evaluate women's anxiety and experience undergoing screening mammography during the COVID-19 pandemic. METHODS: An IRB-approved anonymous survey was administered to women receiving screening mammography across six sites in the U.S. and Singapore from October 7, 2020, to March 11, 2021. Using a 1-5 Likert scale, women rated their pre- and post-visit anxiety regarding having their mammogram during the COVID-19 pandemic, importance of observed COVID-19 precautions, and personal risk factors for breast cancer and severe COVID-19 illness. Post-visit change in anxiety was evaluated. Multivariable logistic regression was used to test associations of pre-visit anxiety with breast cancer and COVID-19 risk factors. RESULTS: In total, 1086 women completed the survey. Of these, 59% (630/1061) had >1 breast cancer risk factor; 27% (282/1060) had >1 COVID-19 risk factors. Forty-two percent (445/1065) experienced pre-visit anxiety. Pre-visit anxiety was independently associated with risk factors for severe COVID-19 (OR for >2 vs 0 risk factors: 2.04, 95% confidence interval [CI]: 1.11-3.76) and breast cancer (OR for >2 vs 0 risk factors: 1.71, 95% CI: 1.17-2.50), after adjusting for age and site. Twenty-six percent (272/1065) of women reported post-visit anxiety, an absolute 16% decrease from pre-visit anxiety (95% CI: 14%-19%, P < 0.001). Provider masking (941/1075, 88%) and physical distancing (861/1085, 79%) were rated as the most important precautions. CONCLUSION: Pre-visit anxiety was associated with COVID-19 or breast cancer risk factors and declined significantly after screening mammography. Provider masking and physical distancing were rated the most important precautions implemented by imaging clinics.