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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.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas , Quimioradioterapia , Fluorodesoxiglucosa F18 , Neoplasias Pulmonares , Aprendizaje Automático , Tomografía de Emisión de Positrones , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/terapia , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/terapia , Heurística , Masculino , Persona de Mediana Edad , Femenino , Resultado del Tratamiento , Anciano , Procesamiento de Imagen Asistido por Computador/métodos

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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.

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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.

Asunto(s)

Carcinoma de Células de Merkel , ADN Tumoral Circulante , Progresión de la Enfermedad , Recurrencia Local de Neoplasia , Neoplasia Residual , Neoplasias Cutáneas , Humanos , Carcinoma de Células de Merkel/sangre , Carcinoma de Células de Merkel/genética , Carcinoma de Células de Merkel/patología , Masculino , Femenino , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Anciano , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Estudios Prospectivos , Persona de Mediana Edad , Pronóstico , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Adulto

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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.

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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.

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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.

Asunto(s)

Presión Sanguínea , Enfermedades de las Arterias Carótidas , Hemorragia , Humanos , Masculino , Femenino , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/complicaciones , Enfermedades de las Arterias Carótidas/fisiopatología , Anciano , Persona de Mediana Edad , Hemorragia/diagnóstico por imagen , Hemorragia/fisiopatología , Progresión de la Enfermedad , Factores de Riesgo , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/fisiopatología , Calcificación Vascular/complicaciones , Placa Aterosclerótica/diagnóstico por imagen , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Imagen por Resonancia Magnética/métodos , Angiografía por Resonancia Magnética

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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.

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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Detección Precoz del Cáncer , Estudios de Seguimiento , Estudios Prospectivos , Proyectos Piloto , Medición de Resultados Informados por el Paciente , Tamizaje Masivo/métodos

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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.

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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.

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Multilingüismo , Humanos , Masculino , Lactante , Femenino , Desarrollo del Lenguaje , Habla/fisiología , Lenguaje Infantil , Adulto

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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.

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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.

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Imagen por Resonancia Magnética , Sistemas de Atención de Punto , Femenino , Humanos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Biopsia

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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.

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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.

Asunto(s)

Enfermedades Autoinmunes , Carcinoma de Células de Merkel , Poliomavirus de Células de Merkel , Neoplasias Cutáneas , Humanos , Carcinoma de Células de Merkel/diagnóstico , Carcinoma de Células de Merkel/patología , Pronóstico , Neoplasias Cutáneas/patología , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/diagnóstico

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BACKGROUND: Merkel cell carcinoma (MCC) is often treated with surgery and postoperative radiation therapy (PORT). The optimal time to initiate PORT (Time-to-PORT [ttPORT]) is unknown. PURPOSE: We assessed if delays in ttPORT were associated with inferior outcomes. METHODS: Competing risk regression was used to evaluate associations between ttPORT and locoregional recurrence (LRR) for patients with stage I/II MCC in a prospective registry and adjust for covariates. Distant metastasis and death were competing risks. RESULTS: The cohort included 124 patients with median ttPORT of 41 days (range: 8-125 days). Median follow-up was 55 months. 17 (14%) patients experienced a LRR, 14 (82%) of which arose outside the radiation field. LRR at 5 years was increased for ttPORT >8 weeks vs ≤ 8 weeks, 28.0% vs 9.2%, P = .006. There was an increase in the cumulative incidence of MCC-specific death with increasing ttPORT (HR = 1.14 per 1-week increase, P = .016). LIMITATIONS: The relatively low number of LRRs limited the extent of our multivariable analyses. CONCLUSIONS: Delay of PORT was associated with increased LRR, usually beyond the radiation field. This is consistent with the tendency of MCC to spread quickly via lymphatics. Initiation of PORT within 8 weeks was associated with improved locoregional control and MCC-specific survival.

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Carcinoma de Células de Merkel , Neoplasias Cutáneas , Humanos , Carcinoma de Células de Merkel/radioterapia , Carcinoma de Células de Merkel/cirugía , Carcinoma de Células de Merkel/patología , Neoplasias Cutáneas/radioterapia , Neoplasias Cutáneas/cirugía , Biopsia del Ganglio Linfático Centinela , Pronóstico , Metástasis Linfática , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias

RESUMEN

PURPOSE: Merkel cell carcinoma (MCC) is a highly immunogenic skin cancer. Although essentially all MCCs are antigenic through viral antigens or high tumor mutation burden, MCC has a response rate of only approximately 50% to PD-(L)1 blockade suggesting barriers to T-cell responses. Prior studies of MCC immunobiology have focused on CD8 T-cell infiltration and their exhaustion status, while the role of innate immunity, particularly myeloid cells, in MCC remains underexplored. EXPERIMENTAL DESIGN: We utilized single-cell transcriptomics from 9 patients with MCC and multiplex IHC staining of 54 patients' preimmunotherapy tumors, to identify myeloid cells and evaluate association with immunotherapy response. RESULTS: Single-cell transcriptomics identified tumor-associated macrophages (TAM) as the dominant myeloid component within MCC tumors. These TAMs express an immunosuppressive gene signature characteristic of monocytic myeloid-derived suppressor cells and importantly express several targetable immune checkpoint molecules, including PD-L1 and LILRB receptors, that are not present on tumor cells. Analysis of 54 preimmunotherapy tumor samples showed that a subset of TAMs (CD163+, CD14+, S100A8+) selectively infiltrated tumors that had significant CD8 T cells. Indeed, higher TAM prevalence was associated with resistance to PD-1 blockade. While spatial interactions between TAMs and CD8 T cells were not associated with response, myeloid transcriptomic data showed evidence for cytokine signaling and expression of LILRB receptors, suggesting potential immunosuppressive mechanisms. CONCLUSIONS: This study further characterizes TAMs in MCC tumors and provides insights into their possible immunosuppressive mechanism. TAMs may reduce the likelihood of treatment response in MCC by counteracting the benefit of CD8 T-cell infiltration. See related commentary by Silk and Davar, p. 1076.

Asunto(s)

Carcinoma de Células de Merkel , Neoplasias Cutáneas , Humanos , Carcinoma de Células de Merkel/tratamiento farmacológico , Carcinoma de Células de Merkel/genética , Carcinoma de Células de Merkel/metabolismo , Receptor de Muerte Celular Programada 1 , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Linfocitos T CD8-positivos , Células Mieloides/metabolismo

RESUMEN

BACKGROUND: Merkel cell carcinoma (MCC) recurs in 40% of patients. In addition to stage, factors known to affect recurrence risk include: sex, immunosuppression, unknown primary status, age, site of primary tumor, and time since diagnosis. PURPOSE: Create a multivariable model and web-based calculator to predict MCC recurrence risk more accurately than stage alone. METHODS: Data from 618 patients in a prospective cohort were used in a competing risk regression model to estimate recurrence risk using stage and other factors. RESULTS: In this multivariable model, the most impactful recurrence risk factors were: American Joint Committee on Cancer stage (P < .001), immunosuppression (hazard ratio 2.05; P < .001), male sex (1.59; P = .003) and unknown primary (0.65; P = .064). Compared to stage alone, the model improved prognostic accuracy (concordance index for 2-year risk, 0.66 vs 0.70; P < .001), and modified estimated recurrence risk by up to 4-fold (18% for low-risk stage IIIA vs 78% for high-risk IIIA over 5 years). LIMITATIONS: Lack of an external data set for model validation. CONCLUSION/RELEVANCE: As demonstrated by this multivariable model, accurate recurrence risk prediction requires integration of factors beyond stage. An online calculator based on this model (at merkelcell.org/recur) integrates time since diagnosis and provides new data for optimizing surveillance for MCC patients.

Asunto(s)

Carcinoma de Células de Merkel , Neoplasias Primarias Desconocidas , Neoplasias Cutáneas , Humanos , Masculino , Carcinoma de Células de Merkel/epidemiología , Carcinoma de Células de Merkel/diagnóstico , Estudios Prospectivos , Neoplasias Primarias Desconocidas/patología , Estadificación de Neoplasias , Pronóstico , Neoplasias Cutáneas/patología , Internet , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos

RESUMEN

PURPOSE: Incorporating coronary CT angiographic (CCTA) imaging into emergency department (ED) workflows has been limited by the need for 24/7 real-time postprocessing. The aim of this study was to determine whether interpretation of transaxial CCTA images alone (limited axial interpretation [LI]) is noninferior to interpretation of combined transaxial and multiplanar reformation images (full interpretation [FI]) in assessing patients with acute chest pain in the ED. METHODS: CCTA examinations from 74 patients were evaluated by two radiologists, one without dedicated CCTA training and one with basic CCTA experience. Each examination was evaluated three times in separate sessions, once by LI and twice by FI, in random order. Nineteen coronary artery segments were rated as having significant stenoses (≥50%) or not. Interreader agreement was assessed using Cohen's κ statistic. The primary analysis was whether the accuracy of LI for detecting significant stenosis was noninferior to that of FI at the patient level (margin = -10%). Secondary analyses included similar analyses of sensitivity and specificity, at both the patient and vessel levels. RESULTS: Interreader agreement for significant stenosis was good for both LI and FI (κ = 0.72 vs 0.70, P = .74). Average accuracy for significant stenosis at the patient level was 90.5% for LI and 91.9% for FI, with a difference of -1.4%. The accuracy of LI was noninferior to FI, because the confidence interval did not include the noninferiority margin. Noninferiority was also found for patient-level sensitivity and for accuracy, sensitivity, and specificity at the vessel level. CONCLUSIONS: LI of the coronary arteries using transaxial CCTA images may be sufficient for the detection of significant coronary artery disease in the ED setting.

Asunto(s)

Angiografía por Tomografía Computarizada , Enfermedad de la Arteria Coronaria , Humanos , Angiografía por Tomografía Computarizada/métodos , Constricción Patológica , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Servicio de Urgencia en Hospital

RESUMEN

The Language ENvironment Analysis system (LENA) records children's language environment and provides an automatic estimate of adult-child conversational turn count (CTC) by automatically identifying adult and child speech in close temporal proximity. To assess the reliability of this measure, we examine correlation and agreement between LENA's CTC estimates and manual measurement of adult-child turn-taking in two corpora collected in the USA: a bilingual corpus of Spanish-English-speaking families with infants between 4 and 22 months (n = 37), and a corpus of monolingual families with English-speaking 5-year-olds (n = 56). In each corpus for each child, 100 30-second segments were extracted from daylong recordings in two ways, yielding a total of 9300 minutes of manually annotated audio. LENA's CTC estimate for the same segments was obtained through the LENA software. The two measures of CTC had low correlations for the segments from the monolingual 5-year-olds sampled in both ways, and somewhat higher correlations for the bilingual samples. LENA substantially overestimated CTC on average, relative to manual measurement, for three out of four analysis conditions, and limits of agreement were wide in all cases. Segment-level analyses demonstrated that accidental contiguity had the largest individual impact on LENA's average CTC error, affecting 12-17% of analyzed segments. Other factors significantly contributing to CTC error were speech from other children, presence of multiple adults, and presence of electronic media. These results indicate wide discrepancies between LENA's CTC estimates and manual CTCs, and call into question the comparability of LENA's CTC measure across participants, conditions, and developmental time points.

Asunto(s)

Multilingüismo , Percepción del Habla , Adulto , Lactante , Humanos , Preescolar , Reproducibilidad de los Resultados , Lenguaje , Habla , Desarrollo del Lenguaje