Volumetric analysis: Rethinking brain metastases response assessment.

Background: The Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM) criteria are the gold standard for assessing brain metastases (BMs) treatment response. However, they are limited by their reliance on 1D, despite the routine use of high-resolution T1-weighted MRI scans for BMs, which allows for 3D measurements. Our study aimed to investigate whether volumetric measurements could improve the response assessment in patients with BMs. Methods: We retrospectively evaluated a dataset comprising 783 BMs and analyzed the response of 185 of them from 132 patients who underwent stereotactic radiotherapy between 2007 and 2021 at 5 hospitals. We used T1-weighted MRIs to compute the volume of the lesions. For the volumetric criteria, progressive disease was defined as at least a 30% increase in volume, and partial response was characterized by a 20% volume reduction. Results: Our study showed that the proposed volumetric criteria outperformed the RANO-BM criteria in several aspects: (1) Evaluating every lesion, while RANO-BM failed to evaluate 9.2% of them. (2) Classifying response effectively in 140 lesions, compared to only 72 lesions classified by RANO-BM. (3) Identifying BM recurrences a median of 3.3 months earlier than RANO-BM criteria. Conclusions: Our study demonstrates the superiority of volumetric criteria in improving the response assessment of BMs compared to the RANO-BM criteria. Our proposed criteria allow for evaluation of every lesion, regardless of its size or shape, better classification, and enable earlier identification of progressive disease. Volumetric criteria provide a standardized, reliable, and objective tool for assessing treatment response.

Growth exponents reflect evolutionary processes and treatment response in brain metastases.

Tumor growth is the result of the interplay of complex biological processes in huge numbers of individual cells living in changing environments. Effective simple mathematical laws have been shown to describe tumor growth in vitro, or simple animal models with bounded-growth dynamics accurately. However, results for the growth of human cancers in patients are scarce. Our study mined a large dataset of 1133 brain metastases (BMs) with longitudinal imaging follow-up to find growth laws for untreated BMs and recurrent treated BMs. Untreated BMs showed high growth exponents, most likely related to the underlying evolutionary dynamics, with experimental tumors in mice resembling accurately the disease. Recurrent BMs growth exponents were smaller, most probably due to a reduction in tumor heterogeneity after treatment, which may limit the tumor evolutionary capabilities. In silico simulations using a stochastic discrete mesoscopic model with basic evolutionary dynamics led to results in line with the observed data.

The Management of Metastatic Spinal Cord Compression in Routine Clinical Practice.

(1) Background: Whether clinical management of spinal metastatic disease (SMD) matches evidence-based recommendations is largely unknown. (2) Patients and Methods: A questionnaire was distributed through Spanish Medical Societies, exploring routine practice, interpretation of the SINS and ESCC scores and agreement with items in the Tokuhashi and SINS scales, and NICE guideline recommendations. Questionnaires were completed voluntarily and anonymously, without compensation. (3) Results: Eighty specialists participated in the study. A protocol for patients with SMD existed in 33.7% of the hospitals, a specific multidisciplinary board in 33.7%, 40% of radiological reports included the ESCC score, and a prognostic scoring method was used in 73.7%. While 77.5% of the participants were familiar with SINS, only 60% used it. The different SINS and ESCC scores were interpreted correctly by 57.5-70.0% and 30.0-37.5% of the participants, respectively. Over 70% agreed with the items included in the SINS and Tokuhashi scores and with the recommendations from the NICE guideline. Differences were found across private/public sectors, hospital complexity, number of years of experience, number of patients with SMD seen annually and especially across specialties. (4) Conclusions: Most specialists know and agree with features defining the gold standard treatment for patients with SCC, but many do not apply them.

A comprehensive dataset of annotated brain metastasis MR images with clinical and radiomic data.

Brain metastasis (BM) is one of the main complications of many cancers, and the most frequent malignancy of the central nervous system. Imaging studies of BMs are routinely used for diagnosis of disease, treatment planning and follow-up. Artificial Intelligence (AI) has great potential to provide automated tools to assist in the management of disease. However, AI methods require large datasets for training and validation, and to date there have been just one publicly available imaging dataset of 156 BMs. This paper publishes 637 high-resolution imaging studies of 75 patients harboring 260 BM lesions, and their respective clinical data. It also includes semi-automatic segmentations of 593 BMs, including pre- and post-treatment T1-weighted cases, and a set of morphological and radiomic features for the cases segmented. This data-sharing initiative is expected to enable research into and performance evaluation of automatic BM detection, lesion segmentation, disease status evaluation and treatment planning methods for BMs, as well as the development and validation of predictive and prognostic tools with clinical applicability.

Growth dynamics of brain metastases differentiate radiation necrosis from recurrence.

Background: Radiation necrosis (RN) is a frequent adverse event after fractionated stereotactic radiotherapy (FSRT) or single-session stereotactic radiosurgery (SRS) treatment of brain metastases (BMs). It is difficult to distinguish RN from progressive disease (PD) due to their similarities in the magnetic resonance images. Previous theoretical studies have hypothesized that RN could have faster, although transient, growth dynamics after FSRT/SRS, but no study has proven that hypothesis using patient data. Thus, we hypothesized that lesion size time dynamics obtained from growth laws fitted with data from sequential volumetric measurements on magnetic resonance images may help in discriminating recurrent BMs from RN events. Methods: A total of 101 BMs from different institutions, growing after FSRT/SRS (60 PDs and 41 RNs) in 86 patients, displaying growth for at least 3 consecutive MRI follow-ups were selected for the study from a database of 1031 BMs. The 3 parameters of the Von Bertalanffy growth law were determined for each BM and used to discriminate statistically PDs from RNs. Results: Growth exponents in patients with RNs were found to be substantially larger than those of PD, due to the faster, although transient, dynamics of inflammatory processes. Statistically significant differences (P < .001) were found between both groups. The receiver operating characteristic curve (AUC = 0.76) supported the ability of the growth law exponent to classify the events. Conclusions: Growth law exponents obtained from sequential longitudinal magnetic resonance images after FSRT/SRS can be used as a complementary tool in the differential diagnosis between RN and PD.

A Critical Appraisal of the Quality of Vertigo Practice Guidelines Using the AGREE II Tool: A EuroAIM Initiative.

OBJECTIVES: The aim of this review is to assess the methodological quality of guidelines for the management of vertigo and dizziness and to compare their recommendations, with specific focus on neuroimaging. DATABASES REVIEWED: MEDLINE, EMBASE, National Guideline Clearinghouse, and National Institute for Health and Clinical Excellence database. METHODS: In March 2022, a systematic search was performed to find practice guidelines of management of vertigo and dizziness. The evaluation of guidelines quality was performed independently by four authors using the AGREE II tool. We excluded from the results those guidelines that were not primarily focused on vertigo and dizziness, such as national/international guidelines in which vertigo and dizziness were only briefly mentioned. RESULTS: Our strategy of literature search identified 161 studies, and 18 guidelines were selected for the appraisal. Only five guidelines reached the acceptance level in the overall result (at least 60%), with three of them reaching the highest scores (at least 80%). The highest scores were found in Domain 6 "Editorial Independence," Domain 1 "Scope and purpose," and Domain 4 "Clarity of presentation" (median value = 66%, 62%, and 61%, respectively). The remaining domains showed a low level of quality: Domain 2 "Stakeholder Involvement," Domain 3 "Rigor of development," and Domain 5 "Applicability" had median values of 27%, 27%, and 22%, respectively. The quality of these guidelines was very low, because of low involvement of multidisciplinary teams in writing guidelines recommendations. CONCLUSION: Considering all guidelines, only three had a "high" overall score, whereas 13 of 18 (72%) of them were rated as of "low" quality. Future guidelines might take this into account to improve clinical applicability.

30 s sit-to-stand power is positively associated with chest muscle thickness in COVID-19 survivors.

INTRODUCTION: After hospitalization, early detection of musculoskeletal sequelae might help healthcare professionals to improve and individualize treatment, accelerating recovery after COVID-19. The objective was to determine the association between the 30s sit-to-stand muscle power (30s-STS) and cross-sectional area of the chest muscles (pectoralis) in COVID-19 survivors. METHOD: This cross-sectional study collected routine data from COVID-19 survivors one month after hospitalization: 1) a chest computed tomography (CT) scan and 2) a functional capacity test (30s-STS). The pectoralis muscle area (PMA) was measured from axial CT images. For each gender, patients were categorized into tertiles based on PMA. The 30s-STS was performed to determine the leg extension power. The allometric and relative STS power were calculated as absolute 30s-STS power normalized to height squared and body mass. The two-way ANOVA was used to compare the gender-stratified tertiles of 30s-STS power variants. RESULTS: Fifty-eight COVID-19 survivors were included (mean age 61.2 ± 12.9 years, 30/28 (51.7%/48.3%) men/women). The two-way ANOVA showed significant differences between the PMA tertiles in absolute STS power (p = .002) and allometric STS power (p = .001). There were no significant gender x PMA tertile interactions (all variables p > .05). The high tertile of PMA showed a higher allometric STS power compared to the low and middle tertile, p = .002 and p = .004, respectively. Absolute STS power and allometric STS power had a moderate correlation with the PMA, r = 0.519 (p < .001) and r = 0.458 (p < .001) respectively. CONCLUSION: The 30s-STS power is associated with pectoralis muscle thickness in both male and female COVID-19 survivors. Thus, this test may indicate global muscle-wasting and may be used as a screening tool for lower extremity functional capacity in the early stages of rehabilitation planning in COVID-19 survivors.

Cribado de cáncer de pulmón: Supervivencia en un amplio programa de detección precoz en España (I-ELCAP) / Lung Cancer Screening: Survival in an Extensive Early Detection Program in Spain (I-ELCAP)

Introducción y objetivo: El cáncer de pulmón (CP) se diagnostica habitualmente en estadios avanzados con una supervivencia media a cinco años del 12%. Ensayos como el National Lung Screening Trial (NLST) y el NEderlands Leuvens longkanker Screenings ONderzoek (NELSON) demuestran una reducción de la mortalidad que justifican la implantación del cribado en población de riesgo. Nuestro objetivo es presentar los resultados de supervivencia del programa de cribado de CP más amplio de España con tomografía computarizada de baja dosis (TCBD). Métodos: Se analizaron los datos del programa Internacional de Detección Precoz de CP (IELCAP) en Valencia, España. Este programa reclutó fumadores o exfumadores con una edad entre 40- 80 años. Se comparan los resultados con otros programas de similar tamaño. Resultados: Un total de 8.278 participantes fueron reclutados con al menos dos rondas de seguimiento, hasta noviembre de 2020 (62,8% varones), realizando una media de seis rondas de cribado por individuo. Diagnosticamos 239 tumores en 12 años de seguimiento. El adenocarcinoma fue el tumor más frecuente con un 61,3% en estadio I. Las tasas de prevalencia e incidencia fueron de 1,5% y 1,4%, respectivamente, con una tasa de detección anual de 0,17. Las tasas de supervivencia cáncer específica a cinco años fueron del 90 y del 80,1% a 10 años. La adherencia fue de 96,84%. Conclusión: La experiencia del programa más amplio de España demuestra que la supervivencia se mejora cuando se realiza en equipos multidisciplinares con experiencia en CP y es similar a programas similares. (AU)

Introduction: Lung cancer (LC) is usually diagnosed at advanced stages with only a 12% 5-year survival. Trials as NLST and NELSON show a mortality decrease, which justifies implementation of lung cancer screening in risk population. Our objective was to show survival results of the largest LC screening program in Spain with low dosage computed tomography (LDCT). Methods: Clinical records from International Early Lung Cancer Detection Program (IELCAP) at Valencia, Spain were analysed. This program recruited volunteers, ever-smokers aged 40-80 years, since 2008. Results are compared to those from other similar sizeable programs. Results: A total of 8278 participants were screened with at least two-rounds until November 2020. A mean of 6 annual screening rounds were performed. We detected 239 tumours along 12-year follow-up. Adenocarcinoma was the most common histology, being 61.3% at stage I. The lung cancer prevalence and incidence proportion was 1.5% and 1.4%, respectively with an annual detection rate of 0.17. One-year survival and 10-year survival were 90% and 80.1%, respectively. Adherence was 96.84%. Conclusion: Largest lung cancer screening in Spain shows that survival is improved when is performed in multidisciplinary team experienced in management of LC, and is comparable to similar screening programs. (AU)

[Translated article] Lung Cancer Screening: Survival in an Extensive Early Detection Program in Spain (I-ELCAP) / Cribado de cáncer de pulmón: supervivencia en un amplio programa de detección precoz en España (I-ELCAP)

Introduction: Lung cancer (LC) is usually diagnosed at advanced stages with only a 12% 5-year survival. Trials as NLST and NELSON show a mortality decrease, which justifies implementation of lung cancer screening in risk population. Our objective was to show survival results of the largest LC screening program in Spain with low dosage computed tomography (LDCT). Methods: Clinical records from International Early Lung Cancer Detection Program (IELCAP) at Valencia, Spain were analysed. This program recruited volunteers, ever-smokers aged 40-80 years, since 2008. Results are compared to those from other similar sizeable programs. Results: A total of 8278 participants were screened with at least two-rounds until November 2020. A mean of 6 annual screening rounds were performed. We detected 239 tumours along 12-year follow-up. Adenocarcinoma was the most common histology, being 61.3% at stage I. The lung cancer prevalence and incidence proportion was 1.5% and 1.4%, respectively with an annual detection rate of 0.17. One-year survival and 10-year survival were 90% and 80.1%, respectively. Adherence was 96.84%. Conclusion: Largest lung cancer screening in Spain shows that survival is improved when is performed in multidisciplinary team experienced in management of LC, and is comparable to similar screening programs. (AU)

Introducción y objetivo: El cáncer de pulmón (CP) se diagnostica habitualmente en estadios avanzados con una supervivencia media a cinco años del 12%. Ensayos como el National Lung Screening Trial (NLST) y el NEderlands Leuvens longkanker Screenings ONderzoek (NELSON) demuestran una reducción de la mortalidad que justifican la implantación del cribado en población de riesgo. Nuestro objetivo es presentar los resultados de supervivencia del programa de cribado de CP más amplio de España con tomografía computarizada de baja dosis (TCBD). Métodos: Se analizaron los datos del programa Internacional de Detección Precoz de CP (IELCAP) en Valencia, España. Este programa reclutó fumadores o exfumadores con una edad entre 40- 80 años. Se comparan los resultados con otros programas de similar tamaño. Resultados: Un total de 8.278 participantes fueron reclutados con al menos dos rondas de seguimiento, hasta noviembre de 2020 (62,8% varones), realizando una media de seis rondas de cribado por individuo. Diagnosticamos 239 tumores en 12 años de seguimiento. El adenocarcinoma fue el tumor más frecuente con un 61,3% en estadio I. Las tasas de prevalencia e incidencia fueron de 1,5% y 1,4%, respectivamente, con una tasa de detección anual de 0,17. Las tasas de supervivencia cáncer específica a cinco años fueron del 90 y del 80,1% a 10 años. La adherencia fue de 96,84%. Conclusión: La experiencia del programa más amplio de España demuestra que la supervivencia se mejora cuando se realiza en equipos multidisciplinares con experiencia en CP y es similar a programas similares. (AU)

Lung Cancer Screening: Survival in an Extensive Early Detection Program in Spain (I-ELCAP). / Cribado de cáncer de pulmón: Supervivencia en un amplio programa de detección precoz en España (I-ELCAP).

INTRODUCTION: Lung cancer (LC) is usually diagnosed at advanced stages with only a 12% 5-year survival. Trials as NLST and NELSON show a mortality decrease, which justifies implementation of lung cancer screening in risk population. Our objective was to show survival results of the largest LC screening program in Spain with low dosage computed tomography (LDCT). METHODS: Clinical records from International Early Lung Cancer Detection Program (IELCAP) at Valencia, Spain were analysed. This program recruited volunteers, ever-smokers aged 40-80 years, since 2008. Results are compared to those from other similar sizeable programs. RESULTS: A total of 8278 participants were screened with at least two-rounds until November 2020. A mean of 6 annual screening rounds were performed. We detected 239 tumours along 12-year follow-up. Adenocarcinoma was the most common histology, being 61.3% at stage I. The lung cancer prevalence and incidence proportion was 1.5% and 1.4%, respectively with an annual detection rate of 0.17. One-year survival and 10-year survival were 90% and 80.1%, respectively. Adherence was 96.84%. CONCLUSION: Largest lung cancer screening in Spain shows that survival is improved when is performed in multidisciplinary team experienced in management of LC, and is comparable to similar screening programs.

Ki-67 immunoexpression and radiological assessment of necrosis improves accuracy of conventional and modified core biopsy systems in predicting the final grade assigned to adult-soft tissue sarcomas. An international collaborative study.

Based on the French Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grading system, this study assesses the accuracy of conventional and modified core biopsy (CB) systems in predicting the final grade (low vs high) assigned to the resected specimen. Substituting Ki-67 immunoexpression for mitotic count, and radiological for histological assessment of necrosis, we used two modified FNCLCC CB grading systems: (1) Ki-67 immunoexpression alone, and (2) Ki-67 plus radiological assessment of necrosis. We graded 199 soft tissue sarcomas (STS) from nine centers, and compared the results for the conventional (obtained from local histopathology reports) and modified CB systems with the final FNCLCC grading of the corresponding resected specimens. Due to insufficient sample quality or lack of available radiologic data, five cases were not evaluated for Ki67 or radiological assessment of necrosis. The conventional FNCLCC CB grading system accurately identified 109 of the 130 high-grade cases (83.8%). The CB grading matched the final FNCLCC grading (low vs high) in 175 (87.9%) of the 199 resected tumors; overestimating the final grade in three cases and underestimating in 21 cases. Modified system 1 (Ki-67) accurately identified 117 of the 130 high-grade cases (90.0%). The CB grading matched the final FNCLCC grading (low vs high) in 175 (89.7%) of the 195 evaluated cases; overestimating seven and underestimating 13 cases. Modified system 2 (Ki-67 plus radiological necrosis) accurately identified 120 of the 130 high-grade cases (92.3%). This last matched the final FNCLCC grading (low vs high) in 177 (91.2%) of the 194 evaluated cases; overestimating seven and underestimating 10 cases. Modified system 2 obtained highest area under ROC curves, although not statistically significant. Underestimated CB grades did not correlate with histological subtypes, although many of the discrepant cases were myxoid tumors (myxofibrosarcomas or myxoid liposarcomas), leiomyosarcomas or undifferentiated pleomorphic/spindle cell sarcomas. Using modified FNCLCC CB grading systems to replace conventional mitotic count and histologic assessment of necrosis may improve the distinction between low and high-grade STS on CB. Our study confirms that classifying grade 1 as low grade and grades 2 and 3 as high grade improves correlation between CB and final grade by up to 21%, irrespective of CB system used. A higher than expected Ki-67 score in a low-grade sarcoma diagnosed on CB should raise concern that a higher-grade component may not have been sampled. Furthermore, correlation of all clinicopathological and radiological findings at multidisciplinary meetings is essential to assess the histological grade on CB as accurately as possible.

Usefulness of ultrasound in dermatofibrosarcoma protuberans and correlation with histopathological findings: A series of 30 cases.

BACKGROUND: Small series of ultrasound findings in dermatofibrosarcoma protuberans (DFSP) have been published, but the usefulness of this technique as a preoperative planning tool for tumor resection has not been studied. MATERIALS AND METHODS: We retrospectively reviewed patients with DFSP at our hospital that underwent ultrasound examination. Depth of invasion was evaluated by ultrasound and histopathology. Accuracy of ultrasound for assessing depth of tumor invasion was estimated. RESULTS: Thirty histopathologically confirmed DFSPs were studied. Classic finger-like projections were observed in 73.3% of cases. A posterior hyperechoic area extending deep into the subcutaneous tissue correlated with the honeycomb DFSP pattern and was observed in 53.3% of patients. Concordance between ultrasound and histopathologic depth measurements was excellent. Lateral tumor extension and Doppler activity were not evaluated in our series. CONCLUSION: Ultrasound showed excellent prediction of depth of invasion. Further studies are required to define the usefulness of ultrasound for determining lateral tumor extension.

Administration of iodinated contrast: What is the risk in cancer patients?

OBJECTIVE: Despite the association between intravenous contrast and kidney injury, few studies exist in oncology. Our objective was to estimate kidney outcomes following iodinated contrast-enhanced computed tomography (CECT) in cancer patients, and to evaluate whether self-assessment questionnaires can identify kidney injury risk factors. METHODS: This prospective observational study included 289 patients who underwent a CECT scan between March and May 2017 in a hospital setting. All patients completed the modified European Society of Urogenital Radiology (ESUR) questionnaire and had an estimated glomerular filtration rate (eGFR) >30 ml/min/1.73 m2 on the day of the examination. Outcomes were followed for 4 months. Univariate and logistic regression analyses were carried out. RESULTS: In the logistic regression analysis, the only variables statistically associated with deterioration in the eGFR were age, (odds ratio (OR) = 1.091, p = 0.003), female sex, (OR 0.22, p = 0.020) and arterial hypertension (AH), (OR = 3.57, p = 0.019). Regarding exitus, only the group with a worse eGFR was close to predictive statistical significance (OR = 2.48, p = 0.09). CONCLUSIONS: The administration of iodinated contrast in cancer patients was not associated with an increase in kidney outcomes. Risk factors in these patients were age, sex and AH.

Universal scaling laws rule explosive growth in human cancers.

Most physical and other natural systems are complex entities composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws relating an observable quantity with a measure of the size of the system. Here we describe the discovery of universal superlinear metabolic scaling laws in human cancers. This dependence underpins increasing tumour aggressiveness, due to evolutionary dynamics, which leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of cancer patients. To explain our observations we put forward increasingly-complex biologically-inspired mathematical models that captured the key processes governing tumor growth. Our models predicted that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws thereby identified allowed us to define a set of metabolic metrics with prognostic value, thus providing added clinical utility to the base findings.