Biliotórax: una entidad rara para un diagnóstico frecuente. Un reporte de caso / Bilothorax: a Rare Entity for a Frequent Diagnosis. A Case Report

Introducción: El biliotórax es una condición infrecuente definida por la presencia de bilis en el espacio pleural. Actualmente, hay alrededor de 70 casos descritos en la litera-tura. Sigue siendo relativamente desconocido, por lo tanto, poco sospechado. Esta entidad suele ser el resultado de una lesión iatrogénica, a menudo secundaria a cirugías o traumatismos del tracto biliar, que conduce a la formación de una fístula pleurobiliar.

Introduction: Bilothorax is a rare condition defined by the presence of bile in the pleural space. Currently, there are around 70 cases described in the literature. It remains relatively unknown and, therefore, little suspected. This entity is usually the result of an iatrogenic injury, often secondary to surgery or trauma to the biliary tract, leading to the formation of a pleurobiliary fistula

Differential Diagnosis of Oral Metastases / Diagnóstico Diferencial de las Metástasis Orales

Metastatic lesions in the mouth can resemble common inflammatory lesions. Therefore, we set out to investigate oral metastases whose clinical and imaging characteristics mimicked those of harmless lesions, confusing and delaying the diagnosis. For this, a systematic review was carried out from case reports, case series, and cross-sectional studies in the PubMed/Medline, Scopus, Embase-via Elsevier, Virtual Health Library, Web of Science, and gray literature, using PICO strategy without period restriction. We assessed the quality of studies using the Joanna Briggs Institute assessment tool. A narrative synthesis of the data was carried out. Association analyses using chi-square and Fisher's exact tests were performed, with statistical significance at p<0.05. Most of the lesions came from the lung, breast, kidneys, liver, and thyroid. They affected mainly the mandibles of men, between the fifth and seventh decades of life, causing osteolysis. In soft tissue, there were firm swellings, associated with bleeding. Limitations regarding the heterogeneity of the included studies and the absence of clinic pathological descriptions of the tumors substantially reduced the chance of statistical analysis of the data. Knowing the different possibilities of clinical presentation of oral and maxillofacial metastases is important for the diagnost ic suspicion to occur and diagnostic errors to be avoided. Thus, treatment is instituted and survival can be extended. Protocol registration: PROSPERO CRD42020200696.

Las lesiones metastásicas en la cavidad oral pueden parecer similares a lesiones inflamatorias comunes. Por ello, nos propusimos investigar metástasis orales cuyas características clínicas e imagenológicas simularan las de lesiones inofensivas, confundiendo y retrasando el diagnóstico. Para ello, se realizó una revisión sistemática a partir de reportes de casos, series de casos y estudios transversales en PubMed/Medline, Scopus, Embase-vía Elsevier, Virtual Health Library, Web of Science y literatura gris, utilizando la estrategia PICO sin restricción de periodo. La calidad de los estudios se evaluó mediante la herramienta de evaluación del Instituto Joanna Briggs. Se realizó una síntesis narrativa de los datos. Se realizaron análisis de asociación mediante chi-cuadrado y prueba exacta de Fisher, con significancia estadística en p<0,05. La mayoría de las lesiones procedían de pulmón, mama, riñones, hígado y tiroides. Afectan principalmente a las mandíbulas de los hombres, entre la quinta y la séptima década de la vida, provocando osteólisis. En los tejidos blandos, había hinchazones firmes, asociadas con sangrado. Las limitaciones con respecto a la heterogeneidad de los estudios incluidos y la ausencia de descripciones clinicopatológicas de los tumores redujeron sustancialmente la posibilidad de realizar un análisis estadístico de los datos. Conocer las diferentes posibilidades de presentación clínica de las metástasis orales y maxilofaciales es importante para que se produzca la sospecha diagnóstica y se eviten errores diagnósticos. Por lo tanto, se instituye el tratamiento y se puede prolongar la supervivencia. Registro de protocolo: PROSPERO CRD42020200696.

Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA.

Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study2. A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120 days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy.

The evolution of non-small cell lung cancer metastases in TRACERx.

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse.

Recent trends of characteristics and treatments in adults with newly diagnosed brain metastases.

OBJECTIVE: We aimed to evaluate recent trends in characteristics and treatments among patients with brain metastases in clinical practice. METHODS: All newly diagnosed patients with brain metastases during 2016-2021 at a single cancer center were enrolled. We collected the detailed features of each patient and estimated the number of candidates considered to meet the following criteria used in common clinical trials: Karnofsky performance status ≥ 70 and mutated non-small cell lung cancer, breast cancer or melanoma. The brain metastases treatments were classified as follows: (i) stereotactic radiosurgery, (ii) stereotactic radiosurgery and systemic therapy, (iii) whole-brain radiotherapy, (iv) whole-brain radiotherapy and systemic therapy, (v) surgery, (vi) immune checkpoint inhibitor or targeted therapy, (vii) cytotoxic agents and (ix) palliative care. Overall survival and intracranial progression-free survival were estimated from brain metastases diagnosis to death or intracranial progression. RESULTS: A total of 800 brain metastases patients were analyzed; 597 (74.6%) underwent radiotherapy, and 422 (52.7%) underwent systemic therapy. In addition, 250 (31.3%) patients were considered candidates for common clinical trials. Compared to 2016, the later years tended to shift from whole-brain radiotherapy to stereotactic radiosurgery (whole-brain radiotherapy: 35.7-29.1% and stereotactic radiosurgery: 33.4-42.8%) and from cytotoxic agents to immune checkpoint inhibitor/targeted therapy (cytotoxic agents: 10.1-5.0 and immune checkpoint inhibitor/targeted therapy: 7.8-10.9%). There was also an increase in the proportion of systemic therapy combined with radiation therapy (from 26.4 to 36.5%). The median overall survival and progression-free survival were 12.7 and 5.3 months, respectively. CONCLUSIONS: This study revealed the diversity of brain metastases patient characteristics, recent changes in treatment selection and the percentage of candidates in clinical trials.

Metastasis prevention: How to catch metastatic seeds.

Despite considerable advances in the evolution of anticancer therapies, metastasis still remains the main cause of cancer mortality. Therefore, current strategies for cancer cure should be redirected towards prevention of metastasis. Targeting metastatic pathways represents a promising therapeutic opportunity aimed at obstructing tumor cell dissemination and metastatic colonization. In this review, we focus on preclinical studies and clinical trials over the last five years that showed high efficacy in suppressing metastasis through targeting lymph node dissemination, tumor cell extravasation, reactive oxygen species, pre-metastatic niche, exosome machinery, and dormancy.

Effects of Chitosan Nanoparticles with Long Synthetic siRNAs Targeting VEGF in Triple-Negative Breast Cancer Cells

Abstract Vascular endothelial growth factor (VEGF) is an essential angiogenic factor in breast cancer development and metastasis. Small interfering RNAs (siRNAs) can specifically silence genes via the RNA interference pathway, therefore were investigated as cancer therapeutics. In this study, we investigated the effects of siRNAs longer than 30 base pairs (bp) loaded into chitosan nanoparticles in triple-negative breast cancer cells, compared with conventional siRNAs. 35 bp long synthetic siRNAs inhibited VEGF gene expression by 51.2% and increased apoptosis level by 1.75-fold in MDA-MB-231 cell lines. Furthermore, blank and siRNA-loaded chitosan nanoparticles induced expression of IFN-γ in breast cancer cells. These results suggest that long synthetic siRNAs can be as effective as conventional siRNAs, when introduced into cells with chitosan nanoparticles

Relato de caso: Carcinoma indiferenciado de sítio primário oculto com metástases para pericárdio e Púrpura trombocitopênica trombótica paraneoplásica / Case report: Undifferentiated carcinoma of occult primary site with metastases to the pericardium and paraneoplastic thrombotic thrombocytopenic purpura

A associação entre neoplasia de sítio primário oculto e manifestações paraneoplásicas é um desafio diagnóstico e terapêutico. Este relato de caso descreve uma paciente com púrpura trombocitopênica trombótica (PTT) paraneoplásica como manifestação de um câncer primário oculto atendida pelo setor de Oncologia Clínica do Hospital do Servidor Público Municipal. A paciente apresentou queda importante da funcionalidade em pouco tempo devido a descompensação da neoplasia de base, evoluindo à óbito em poucos meses sem conseguir realizar qualquer tipo de tratamento. Este relato enfatiza a importância da avaliação clínica precisa e abrangente, além da abordagem multidisciplinar nos pacientes oncológicos que tanto sofrem com o estigma dessa doença. Palavras-chave: Neoplasia de Sítio Primário Oculto. Púrpura Trombocitopênica Trombótica Paraneoplásica. Metástases Cardíacas. Oncologia.

Effect of Electronic Symptom Monitoring on Patient-Reported Outcomes Among Patients With Metastatic Cancer: A Randomized Clinical Trial.

Importance: Electronic systems that facilitate patient-reported outcome (PRO) surveys for patients with cancer may detect symptoms early and prompt clinicians to intervene. Objective: To evaluate whether electronic symptom monitoring during cancer treatment confers benefits on quality-of-life outcomes. Design, Setting, and Participants: Report of secondary outcomes from the PRO-TECT (Alliance AFT-39) cluster randomized trial in 52 US community oncology practices randomized to electronic symptom monitoring with PRO surveys or usual care. Between October 2017 and March 2020, 1191 adults being treated for metastatic cancer were enrolled, with last follow-up on May 17, 2021. Interventions: In the PRO group, participants (n = 593) were asked to complete weekly surveys via an internet-based or automated telephone system for up to 1 year. Severe or worsening symptoms triggered care team alerts. The control group (n = 598) received usual care. Main Outcomes and Measures: The 3 prespecified secondary outcomes were physical function, symptom control, and health-related quality of life (HRQOL) at 3 months, measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference [MCID], 2-7 for physical function; no MCID defined for symptom control or HRQOL). Results on the primary outcome, overall survival, are not yet available. Results: Among 52 practices, 1191 patients were included (mean age, 62.2 years; 694 [58.3%] women); 1066 (89.5%) completed 3-month follow-up. Compared with usual care, mean changes on the QLQ-C30 from baseline to 3 months were significantly improved in the PRO group for physical function (PRO, from 74.27 to 75.81 points; control, from 73.54 to 72.61 points; mean difference, 2.47 [95% CI, 0.41-4.53]; P = .02), symptom control (PRO, from 77.67 to 80.03 points; control, from 76.75 to 76.55 points; mean difference, 2.56 [95% CI, 0.95-4.17]; P = .002), and HRQOL (PRO, from 78.11 to 80.03 points; control, from 77.00 to 76.50 points; mean difference, 2.43 [95% CI, 0.90-3.96]; P = .002). Patients in the PRO group had significantly greater odds of experiencing clinically meaningful benefits vs usual care for physical function (7.7% more with improvements of ≥5 points and 6.1% fewer with worsening of ≥5 points; odds ratio [OR], 1.35 [95% CI, 1.08-1.70]; P = .009), symptom control (8.6% and 7.5%, respectively; OR, 1.50 [95% CI, 1.15-1.95]; P = .003), and HRQOL (8.5% and 4.9%, respectively; OR, 1.41 [95% CI, 1.10-1.81]; P = .006). Conclusions and Relevance: In this report of secondary outcomes from a randomized clinical trial of adults receiving cancer treatment, use of weekly electronic PRO surveys to monitor symptoms, compared with usual care, resulted in statistically significant improvements in physical function, symptom control, and HRQOL at 3 months, with mean improvements of approximately 2.5 points on a 0- to 100-point scale. These findings should be interpreted provisionally pending results of the primary outcome of overall survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03249090.

Resultados del tratamiento a pacientes con cáncer anal en el Hospital Universitario Clínico Quirúrgico "Comandante Manuel Fajardo" / Results of Treating Of Anal Cancer Patients at Comandante Manuel Fajardo Surgical Clinical University Hospital

Introducción: El cáncer anal es el de menor incidencia del tubo digestivo, pero en los últimos años ha presentado un discreto incremento. Objetivo: Identificar los resultados del tratamiento empleado para el cáncer anal en el Servicio de Coloproctología del Hospital Universitario Clínico Quirúrgico "Comandante Manuel Fajardo". Métodos: Se realizó un estudio descriptivo y observacional con pacientes diagnosticados y tratados por cáncer anal en el período 2014-2019. Se estudiaron variables como antecedentes patológicos, factores de riesgo, síntomas, estadio de la enfermedad, tratamientos, entre otras. Resultados: La media de edad fue 58,4±14,7 años y el 75,3 por ciento fueron mujeres. El 52,1 por ciento presentaban antecedentes patológicos y el factor de riesgo más frecuente fue la edad (> 50 años: 80,8 por ciento). La localización más usual fue en el conducto anal y los estadios II y III. El sangrado se manifestó en el 58,9 por ciento de los pacientes. Se aplicó como tratamiento quimiorradioterapia (87,7 por ciento), exéresis local (17,8 por ciento) y cirugía abdominoperineal (8,2 por ciento). Se realizó colostomía al 14 por ciento de los individuos y el 72,6 por ciento estuvieron libres de colostomía más de un año. El tiempo libre de colostomía fue de 87,5 por ciento, con tratamiento de 5 años y más. De los pacientes fallecidos (24,7 por ciento), en el 55,6 por ciento la causa fue progresión de la enfermedad y la metástasis más frecuente fue la hepática. Conclusiones: La quimiorradioterapia fue el principal tratamiento con el que se obtuvo una aceptable tasa de sobrevida en los pacientes con cáncer anal(AU)

Introduction: Anal cancer is the one with the lowest incidence of the digestive tract, but in recent years it has slightly increased. Objective: To identify the results of the treatment used for anal cancer in the Coloproctology Service of Comandante Manuel Fajardo Surgical Clinical University Hospital. Methods: A descriptive and observational study was carried out with patients diagnosed and treated for anal cancer in the 2014-2019 period. Variables such as pathological history, risk factors, symptoms, stage of the disease, treatments, among others, were studied. Results: The mean age was 58.4 ± 14.7 years and 75.3 percent were women. 52.1 percent had pathological antecedents and the most frequent risk factor was age (> 50 years: 80.8 percent). The most usual location was in the anal canal and stages II and III. Bleeding appeared in 58.9 percent of the patients. Chemoradiation therapy (87.7 percent), local exeresis (17.8 percent) and abdominoperineal surgery (8.2 percent) were applied. Colostomy was performed in 14 percent of individuals; 72.6 percent were free of colostomy for more than one year. The colostomy-free time was 87.5 percent, with treatment of 5 years and more. 24.7 percent died, the disease progression was the cause of death in 55.6 percent of the diseased subjects, while the most frequent cause was liver metastasis. Conclusions: Chemoradiotherapy was the main treatment with which an acceptable survival rate was obtained in patients with anal cancer(AU)

Epidemiological Profile of 96 Intracranial Tumors Treated in a Single Reference Center

Objectives The present study aims to categorize the prevalence of intracranial tumors surgically treated at the neurosurgery service of Hospital Universitário Evangélico Mackenzie (HUEM) between 2016 and 2018. Material and Methods This survey included patients surgically treated due to primary or metastatic intracranial neoplasia between 2016 and 2018 at a referral center in the city of Curitiba. These patients were analyzed for epidemiological, histopathological, and topographic data, and they underwent an assessment of the outcome at the time of hospital discharge. Results Atotal of 96patientsmet the inclusion criteria. Themost prevalent tumorwas the glioma, with 39.6% of the sample, with glioblastoma being themost prevalent histological type. Brainmetastases andmeningiomas represented, respectively, 21.9%and 18.8%of the total. There was a predominance of supratentorial and intra-axial tumors in our sample. Conclusion Glioma was the most commonly found tumor, directly associated with high morbidity and mortality. The development of new and more effective drugs with action directed at themolecular level of intracranial tumorsmay be the path to a longer survival and improvement in the quality of life of these patients.

Intraoperative Molecular Analysis of Total Tumor Load in Sentinel Lymph Node: A Predictor of Axillary Status in Early Breast Cancer.

BACKGROUND: Axillary lymph node dissection (ALND) remains the standard of care in breast cancer patients with positive sentinel lymph node (SLN). However, approximately 40-60% of patients with positive SLNs have not developed to non-SLN metastasis and ALND seems to be an overtreatment. The purpose of this study was to analyze predictors and define a specific cut-off of total tumor load (TTL) of CK19 that can be used as a predictive factor of non-SLN metastasis in early breast cancer patients. MATERIALS AND METHODS: The records of 238 patients with cT1-3N0 breast cancer who had an intraoperative SLN evaluation performed through One-Step nucleic acid (OSNA) assay at Songklanagarind Hospital between 1 January 2015 and 31 December 2019 were examined. Univariate and Multivariate analysis was used to identify clinicopathologic features in SLN-positive patients that predict metastasis to non-SLNs. Finally, receiver operative characteristics (ROC) curves were used to choose an optimal TTL cut-off value. RESULTS: Of a total of 110 patients who had a positive SLN, only 48 (43.64%) were found to have positive nodes in non-SLN. Multivariate analysis revealed that lymphovascular invasion, type of SLN metastasis and SLN TTL (copies/µL) were independent predictors of positive non-SLNs.  TTL cut-off value was 19,000 copies/µL, with an AUC of 0.838 with 72.7% sensitivity and 84.7% specificity to predict non-SLN metastasis. CONCLUSIONS: The likelihood of positive non-SLNs in patients who showed a positive SLN correlates with lymphovascular invasion, type of SLN metastasis and SLN TTL (copies/µL). Our result revealed that the patients with a SLN TTL ≥19,000 copies/µl continue to attract the recommendation to proceed with ALND. This cut-off value can then help clinicians to assess which patients would benefit from ALND.

Pretreatment Neutrophil Count and Platelet-lymphocyte Ratio as Predictors of Metastasis in Patients With Osteosarcoma.

BACKGROUND/AIM: Systemic inflammation responses have been associated with cancer development, progression and metastasis. Little is known about the risk of metastasis based on inflammatory-based scores in patients with osteosarcoma. PATIENTS AND METHODS: A total of 65 osteosarcoma patients without metastasis at presentation were enrolled in this retrospective study. All had been diagnosed histologically, and their laboratory data at the first visit were collected from medical records. The inflammation-based scores, tumor size, location, staging, pathological fracture, treatment methods, follow-up periods, and metastasis-free duration were evaluated. RESULTS: A multivariate Cox regression analysis revealed that a high platelet-lymphocyte ratio (PLR) >116 [hazard ratio (HR)=3.8, 95% confidence interval =1.5-9.3; p<0.01], and neutrophil count (NC) ≤4,030/µl (HR=4.5, 95%CI=1.7-12.3; p<0.01), were independent risk factors significantly associated with metastasis of osteosarcoma patients. CONCLUSION: The combination of a high PLR >116 and NC ≤4,030/µl before treatment was a useful inflammatory-based prognostic indicator for metastasis in patients with osteosarcoma.

Prognostic role of 11C-choline PET/CT scan in patients with metastatic castrate resistant prostate cancer undergoing primary docetaxel chemotherapy.

BACKGROUND: We sought to assess the prognostic utility of 11C-choline positron emission tomography/computed tomography (PET/CT) in patients with metastatic castrate resistant prostate cancer (mCRPC) undergoing primary docetaxel chemotherapy. METHODS: We performed a single institution retrospective analysis of 77 mCRPC patients who were treated with 6 cycles of docetaxel chemotherapy, and who also underwent 11C-choline PET/CT scans at baseline (before chemotherapy), mid-course (after 3 cycles), and posttherapy (after 6 cycles). We evaluated treatment response based on percent change in blood pool-corrected maximum standardized uptake value (SUVmax) of the target lesion on PET/CT, as well as percent change in serum prostate specific antigen (PSA). Logistic regression analysis was used to identify factors associated with complete treatment response. Progression free survival (PFS) analysis was performed using log-rank test and shown on Kaplan-Meier plot. RESULTS: Percent change in blood pool-corrected SUVmax on mid-course scan was a significant predictor of complete response (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.96-0.99, p = .0003), whereas percent change in PSA was not (OR: 0.99, 95% CI: 0.99-1.01, p = .6025). 57 of 77 patients (74%) achieved ≥20% reduction in blood pool-corrected SUVmax on mid-course; these patients were 3.6 times more likely to achieve complete response after full 6 cycles of docetaxel chemotherapy, compared to patients with <20% reduction in blood pool-corrected SUVmax (OR: 3.56, 95% CI: 1.04-16.52, p = .0420). Median PFS in the complete response group was 35.1 months (95% CI: 26.0-52.7 months), compared to 9.4 months (95% CI: 6.9-13.0 months) in the incomplete response group (p = .0005). CONCLUSIONS: Our study showed that mid-course and posttherapy 11C-choline PET/CT evaluation for mCRPC patients undergoing primary docetaxel chemotherapy can predict full course treatment response and PFS, respectively. 11C-choline PET/CT imaging may provide valuable prognostic information to guide treatment choices for patients with mCRPC.

Revisiting the AJCC staging system of adrenocortical carcinoma.

OBJECTIVE: To evaluate the performance characteristics of AJCC 7th and 8th staging systems among patients with adrenal cortical carcinoma. METHODS: Surveillance, Epidemiology, and End Results (SEER) 18-registry was accessed and patients with adrenocortical carcinoma who were diagnosed 2010-2015 with complete information about AJCC 7th staging system were included. AJCC 8th staging system information was then reconstructed for each patient using available TNM staging variables. Kaplan-Meier overall survival estimates, multivariable Cox regression analysis, and concordance index (C-statistic) were used to examine the performance characteristics of both staging systems. RESULTS: A total of 574 patients with a diagnosis of adrenocortical carcinoma were included in the current analysis. Using Kaplan-Meier survival estimates, overall survival was compared among different AJCC stages for both versions; and the P value was significant (< 0.001) for both comparisons. C-statistic was then calculated for both staging systems and the results were as follows: for AJCC 7th version: 0.726 (95% CI 0.683-0.769); and for AJCC 8th version: 0.745 (95% CI 0.704-0.786). Patients with M1 disease (stage IV according to AJCC 8th edition) were then divided according to the extent of distant metastases into single versus multiple sites of metastases. Using Kaplan-Meier survival estimates, patients with a single site of metastases have better overall survival (P = 0.006). A C-statistic for a hypothetical modification of AJCC 8th staging system subdividing stage IV patients into IVA and IVB based on the number of metastatic sites was: 0.753 (95% CI 0.713-0.794). CONCLUSIONS: There is a minimal difference in the prognostic performance between both versions of the AJCC staging system. Subdivision of stage IV cancer into stage IVA and IVB (according to the number of organs with metastatic deposits) should be considered in subsequent versions of adrenocortical carcinoma staging.

Overall and progression-free survival of Afro-Caribbean men with metastatic castration-resistant prostate cancer (mCRPC).

INTRODUCTION: Several studies in the Caucasian population have shown the benefit of using docetaxel, abiraterone, or enzalutamide for patients with metastatic prostate cancer at the castration-resistant stage (mCRPC). However, there are no strong data for men of African ancestry. The objective of this study was to estimate the overall and progression-free survival of patients according to these treatments at the mCRPC stage. PATIENTS AND METHODS: This was a monocentric retrospective study that consecutively included 211 men with mCRPC between June 1, 2009 and August 31, 2020. The primary end point was overall survival (OS). The secondary end point was progression-free survival. Kaplan-Meier survival and Cox proportional hazard analyses were performed. RESULTS: The present study included 180 patients for analyses. There was no difference in OS (log-rank test = 0.73), with a median follow-up of 20.7 months, regardless of the treatment administered in the first line. Men with mCRPC who received hormonotherapy (abiraterone or enzalutamide) showed better progression-free survival than those who received docetaxel (log-rank test = 0.004), with a particular interest for abiraterone hazard ratio (HR) = 0.51 (95% confidence interval: 0.39-0.67). The patient characteristics were similar, except for bone lesions, irrespective of the treatment administered in the first line. After univariate then multivariate analysis, only World Health Organization status and metastases at diagnosis were significantly associated with progression. CONCLUSION: Our results suggest the use of hormonotherapy (abiraterone or enzalutamide) with a tendency for abiraterone in first line for men with African ancestry at the mCRPC stage.

Incorporating artificial intelligence in urology: Supervised machine learning algorithms demonstrate comparative advantage over nomograms in predicting biochemical recurrence after prostatectomy.

OBJECTIVE: After radical prostatectomy (RP), one-third of patients will experience biochemical recurrence (BCR), which is associated with subsequent metastasis and cancer-specific mortality. We employed machine learning (ML) algorithms to predict BCR after RP, and compare them with traditional regression models and nomograms. METHODS: Utilizing a prospective Uro-oncology registry, 18 clinicopathological parameters of 1130 consecutive patients who underwent RP (2009-2018) were recorded, yielding over 20,000 data points for analysis. The data set was split into a 70:30 ratio for training and validation. Three ML models: Naïve Bayes (NB), random forest (RF), and support vector machine (SVM) were studied, and compared with traditional regression models and nomograms (Kattan, CAPSURE, John Hopkins [JHH]) to predict BCR at 1, 3, and 5 years. RESULTS: Over a median follow-up of 70.0 months, 176 (15.6%) developed BCR, at a median time of 16.0 months (interquartile range [IQR]: 11.0-26.0). Multivariate analyses demonstrated strongest association of BCR with prostate-specific antigen (PSA) (p: 0.015), positive surgical margins (p < 0.001), extraprostatic extension (p: 0.002), seminal vesicle invasion (p: 0.004), and grade group (p < 0.001). The 3 ML models demonstrated good prediction of BCR at 1, 3, and 5 years, with the area under curves (AUC) of NB at 0.894, 0.876, and 0.894, RF at 0.846, 0.875, and 0.888, and SVM at 0.835, 0.850, and 0.855, respectively. All models demonstrated (1) robust accuracy (>0.82), (2) good calibration with minimal overfitting, (3) longitudinal consistency across the three time points, and (4) inter-model validity. The ML models were comparable to traditional regression analyses (AUC: 0.797, 0.848, and 0.862) and outperformed the three nomograms: Kattan (AUC: 0.815, 0.798, and 0.799), JHH (AUC: 0.820, 0.757, and 0.750) and CAPSURE nomograms (AUC: 0.706, 0.720, and 0.749) (p < 0.001). CONCLUSION: Supervised ML algorithms can deliver accurate performances and outperform nomograms in predicting BCR after RP. This may facilitate tailored care provisions by identifying high-risk patients who will benefit from multimodal therapy.

Avaliação do tratamento quimioterápico paliativo com o esquema LDE- paclitaxel em pacientes portadores de metástases ósseas por neoplasia maligna / Evaluation of palliative chemotherapy treatment with the LDEpaclitaxel regimen in patients with bone metastases from malignant neoplas

Introdução: Pacientes com câncer em estádios avançados e metástases ósseas frequentemente não apresentam condições clínicas para a realização de esquemas quimioterápicos convencionais subsequentes, restringindo as opções de tratamento. Anteriormente, demonstramos que nanopartículas artificiais lipídicas (LDE), semelhantes à lipoproteína de baixa densidade (LDL) rica em colesterol, são captadas por tecidos malignos, e quando associadas aos quimioterápicos, após injeção pela via endovenosa, reduz drasticamente a toxicidade do tratamento. Os objetivos deste presente estudo foram avaliar a resposta clínica ao tratamento quimioterápico com paclitaxel (PTX) associado à LDE; avaliar as toxicidades clínicas e laboratorial, e a capacidade da associação LDE-PTX em reduzir a dor oncológica relacionada às metástases ósseas em pacientes com carcinoma de mama, próstata e pulmão, previamente tratados e não elegíveis para tratamento quimioterápico convencional subsequente. Métodos: Dezoito pacientes (8 com câncer de mama, 5 de próstata e 5 de pulmão) com metástases ósseas foram incluídos. O tratamento consistiu no esquema LDE-PTX na dose convencional do PTX (175 mg/m2 de superfície corpórea de 3/3 semanas) e os pacientes foram avaliados por resposta clínica, redução da dor óssea, uso de medicamentos opióides, e ocorrência de fraturas ósseas patológicas. Resultados: No total, 104 ciclos de quimioterapia foram realizados, e nenhum paciente apresentou toxicidade clínica, laboratorial, assim como não houve fraturas patológicas. Dos 18 pacientes incluídos, 9 tiveram sobrevida livre de progressão de doença 6 meses. Houve em todos os pacientes redução da dor óssea, permitindo substituição da medicação opióide por analgésico não opióide. Conclusão: A melhora significativa na dor óssea sem que tenha ocorrido toxicidade do tratamento, e o tempo de não progressão de doença 6 meses na metade dos pacientes sugere que esses pacientes tenham se beneficiado consistentemente do tratamento com a LDE-PTX. Portanto, a LDE-PTX pode tornar- se uma opção terapêutica interessante em pacientes com carcinomas de próstata, mama ou pulmão em estágios avançados e sem condições clínicas de se submeterem a outros esquemas quimioterápicos convencionais

Introduction: Patients with advanced cancer and bone metastases usually do not have clinical conditions to perform additional conventional chemotherapy regimens, restricting treatment options. Previously, we showed that lipid core nanoparticles (LDE), similar to cholesterol-rich low-density lipoprotein (LDL), are taken up by malignant tissues, and when associated to chemotherapy, after endovenous injection, it drastically decreases the toxicity of the treatment. The objectives of this study were to evaluate the clinical response to chemotherapy treatment with paclitaxel (PTX) associated with LDE; to evaluate the clinical and laboratorial toxicities, and the ability of the LDE-PTX to reduce cancer pain related to bone metastases in patients with breast, prostate or lung carcinoma, previously treated and not eligible for subsequent conventional chemotherapy treatment. Methods: Eighteen patients (8 with breast cancer, 5 with prostate and 5 with lung) with bone metastases were included. Treatment consisted of the LDE-PTX regimen at a conventional dose of PTX (175 mg/m2 body surface area, 3/3 weeks) and patients were evaluated for clinical response, reduction in bone pain, use of opioid medications, and the occurrence of pathological bone fractures. Results: In total, 104 chemotherapy cycles were performed, and none of the patients showed clinical or laboratorial toxicities, as well as there were no pathological fractures. Of the 18 patients evaluated, 9 had progression-fee survival 6 months. Patients had decrease in bone pain allowing replacement of opioid medication by another non-opioid analgesic. Conclusion: Significant improvement in bone pain without treatment toxicity, and time to disease progression of 6 months in half of the patients suggest that these patients have consistently benefited with LDE-PTX treatment. Therefore, LDE-PTX may become an interesting therapeutic option in patients with advanced stage of prostate, breast or lung carcinomas and without clinical conditions to undergo other conventional chemotherapy regimens

Single-center, retrospective study on changes in pain-relieving therapy after bone metastasis detection by bone scintigraphy in prostate cancer patients

Abstract Whole-body bone scintigraphy (WB-BS) is used for detecting and monitoring metastatic spread of prostate cancer (PCa) and to investigate bone pain episodes. To investigate the impact of a positive WB-BS on pain-relieving medicine prescription in PCa patients, a single-center, retrospective cohort study with PCa patients classified as positive for bone metastases (BM) by WB-BS was conducted. Demographic, clinical, and ambulatory pain-relieving medicine prescription data were evaluated. Pain-relieving medicines were categorized according to the WHO 'Analgesic Ladder'. Regimens adopted before and after WB-BS were compared. Differences were considered significant at p<0.05. A total of 180 PCa patients were diagnosed with BM, 64.4% of whom were ≥65 years of age. Thirty-three patients were prescribed analgesics only after WB-BS, mostly including NSAIDs and weak opioids. Pain-relieving prescription changed after WB-BS in patients with prescriptions before and after WB-BS, with a reduction in NSAIDs and adjuvants and an increase in weak and strong opioids. In addition, 40% of patients with WHO analgesic step 1 drugs and 21.7% of patients with WHO step 2 drugs before WB-BS changed to other WHO steps after WB-BS. Pain-relieving prescriptions changed after a positive WB-BS, providing evidence that it could contribute to clinical management of painful metastatic PCa patients.