Malignant pleural mesothelioma: Description of pleural decortication and hyperthermic chemotherapy technique in multimodal therapy.

The current treatment for mesothelioma, in selected cases, consists of extended pleurodecortication and intrathoracic hyperthermic chemotherapy. This technique is laborious and detailed and must be followed step by step to achieve good results. We present the case of a patient with epithelioid mesothelioma meeting surgical criteria who underwent the mentioned technique, experiencing an adequate postoperative period and an early discharge. This experience demonstrates that the technique is safe when performed in centres with experience and the means to address this complex pathology.

Multidisciplinary approach for locally advanced non-small cell lung cancer (NSCLC): 2023 expert consensus of the Spanish Lung Cancer Group GECP.

INTRODUCTION: Recent advances in the treatment of locally advanced NSCLC have led to changes in the standard of care for this disease. For the selection of the best approach strategy for each patient, it is necessary the homogenization of diagnostic and therapeutic interventions, as well as the promotion of the evaluation of patients by a multidisciplinary oncology team. OBJECTIVE: Development of an expert consensus document with suggestions for the approach and treatment of locally advanced NSCLC leaded by Spanish Lung Cancer Group GECP. METHODS: Between March and July 2023, a panel of 28 experts was formed. Using a mixed technique (Delphi/nominal group) under the guidance of a coordinating group, consensus was reached in 4 phases: 1. Literature review and definition of discussion topics 2. First round of voting 3. Communicating the results and second round of voting 4. Definition of conclusions in nominal group meeting. Responses were consolidated using medians and interquartile ranges. The threshold for agreement was defined as 85% of the votes. RESULTS: New and controversial situations regarding the diagnosis and management of locally advanced NSCLC were analyzed and reconciled based on evidence and clinical experience. Discussion issues included: molecular diagnosis and biomarkers, radiologic and surgical diagnosis, mediastinal staging, role of the multidisciplinary thoracic committee, neoadjuvant treatment indications, evaluation of response to neoadjuvant treatment, postoperative evaluation, and follow-up. CONCLUSIONS: Consensus clinical suggestions were generated on the most relevant scenarios such as diagnosis, staging and treatment of locally advanced lung cancer, which will serve to support decision-making in daily practice.

Starting a robotic thoracic surgery program: From wedge resection to sleeve lobectomy in six months. Initial conclusions / Inicio de un programa de cirugía torácica robótica: de resección en cuña a lobectomía con broncoplastia en seis meses. Conclusiones iniciales

Introduction: Robot-assisted thoracic surgery (RATS) is a rapidly expanding technique. In our study, we aimed to analyze the results of the process to adopt robotic surgery in our Department of Thoracic Surgery. Methods: This is an intention-to-treat analysis of a series of consecutive patients operated on using the RATS approach in our hospital from January 2021 to March 2022. Data were registered for patient characteristics, type of surgery, operative times, conversion rate, chest tube duration, length of hospital stay and complications. The IBM SPSS® statistical software was used for the statistical analysis. A cumulative sum analysis of the operating time was performed to define the learning curve. Results: During the study period, 51 patients underwent robotic surgery, including pulmonary and non-pulmonary interventions. In addition, 15 patients (29.4%) underwent non-pulmonary interventions: one pleural (2%), 2 diaphragmatic (3.9%), and 12 mediastinal (23.5%). Among the mediastinal surgeries, one conversion was necessary (8.3%) for a complex vascular malformation, and 11 were completed by RATS, including 7 (58.3%) thymomas, 3 (25%) pleuro-pericardial cysts, and one (8.3%) neurogenic tumor. Mean operative time was 141 min (104–178), mean chest tube duration was 0.9 days (0–2), and mean length of stay was 1.45 days (1–2). Thirty-six patients underwent lung surgery (70.6%). The complete RATS resections (34; 94.4%) included: 3 wedge resections (11.1%), 2 segmentectomies (3.7%), 28 lobectomies (81.5%), and one sleeve lobectomy (3.7%). Mean surgery time was 194.56 min (141–247), chest tube duration was 3.92 days (1–8), and length of stay was 4.6 days (1–8). Complications occurred in 4 patients (11.1%). No 90-day mortalities were registered. (AU)

Introducción: La cirugía torácica asistida por robot (RATS) es una técnica en rápida expansión. Nuestro objetivo fue analizar el resultado del proceso de adopción de la cirugía robótica en nuestro Departamento de Cirugía Torácica. Métodos: Este es un análisis por intención de tratamiento de una serie de pacientes consecutivos operados mediante el método RATS en nuestro centro desde enero de 2021 a marzo de 2022. Se registraron las características de los pacientes, tipo de cirugía, tiempos operatorios, tasa de conversión, duración del drenaje torácico, estancia hospitalaria y complicaciones. Para el análisis estadístico se utilizó el software IBM SPSS®. Se realizó un análisis de suma acumulada del tiempo de operación para definir la curva de aprendizaje. Resultados: Durante el periodo de estudio, 51 pacientes fueron sometidos a cirugía robótica.15 pacientes (29,4%) fueron sometidos a intervenciones no pulmonares: 1 pleural (2%), 2 diafragmáticas (3,9%) y 12 mediastínicas (23,5%). Entre las cirugías mediastínicas, fue necesaria una conversión (8,3%) por malformación vascular compleja y 11 fueron completadas por RATS, incluidos 7 (58,3%) timomas, 3 (25%) quistes pleuro-pericárdicos y 1 (8,3%) tumores neurogénicos. El tiempo operatorio medio fue de 141 minutos [104–178], la duración media del tubo torácico fue de 0,9 días [0–2] y la estancia media fue de 1,45 días [1–2]. 36 pacientes tuvieron cirugías pulmonares (70,6%). Las resecciones RATS completas (34; 94,4%) incluyeron: 3 resecciones en cuña (11,1%), 2 segmentectomías (3,7%), 28 lobectomías (81,5%) y 1 lobectomía con broncoplastia (3,7%). El tiempo medio de cirugía fue de 194,56 minutos [141–247], la duración del tubo torácico fue de 3,92 días [1–8] y la estancia hospitalaria fue de 4,6 días [1–8]. No se registró mortalidad a los 90 días. (AU)

Prospective Assessment of Bone Metabolism Biomarkers and Survival in Metastatic Castration-resistant Prostate Cancer Patients Treated with Radium-223: The PRORADIUM Study.

BACKGROUND: Radium-223 is an active therapy option for bone metastatic castration-resistant prostate cancer (mCRPC). The lack of adequate biomarkers for patient selection and response assessment are major drawbacks for its use. OBJECTIVE: To assess the prognostic value of bone metabolism biomarkers (BMBs) in ra-223-treated mCRPC patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of mCRPC patients treated with Ra-223 (PRORADIUM study: NCT02925702) was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main objective of the study was to evaluate the association between high (≥median) baseline values in at least three bone formation (bone alkaline phosphatase [BAP] and C-terminal type-I collagen propeptide) and bone resorption (N-terminal telopeptide and pyridinoline) biomarkers, and survival. The independent prognostic value of each BMB was also assessed. The association with time to radiographic, clinical, and prostate-specific antigen (PSA) progression; time to skeletal-related events; and PSA response were secondary objectives. Multivariable (MV) Cox-regression models were evaluated. RESULTS AND LIMITATIONS: A total of 169 patients were included. Of the patients, 70.4% received Ra-223 in second/third line; 144 (85.2%) were Eastern Cooperative Oncology Group 0-1, 126 (74.6%) were in pain, and 80 (47.5%) had more than ten bone metastases. Sixty-seven (39.6%) patients had elevation in at least three BMBs. The median overall survival was 12.1 mo (95% confidence interval [CI]: 10-14.7). No association was observed with other treatment-related secondary outcome parameters. Patients with high values in three or more BMBs had significantly worse survival (9.9 vs 15.2 mo; hazard ratio [HR]: 1.8 [95% CI: 1.3-2.5]; p < 0.001) in the univariate analysis, but not independent in the MV analysis (HR: 1.33; 95% CI: 0.89-2; p = 0.181). High baseline BAP was the only biomarker associated with survival in the MV model (HR: 1.89; 95% CI: 1.28-2.79; p = 0.001). Addition of BAP to the MV clinical model increased the area under the receiver operating characteristic curve 2-yr value from 0.667 to 0.755 (p = 0.003). CONCLUSIONS: Biomarkers of bone formation, especially BAP, have prognostic value in mCRPC patients treated with radium-223. Its predictive value remains to be assessed, ideally in prospective, adequately powered, randomised clinical trials. PATIENT SUMMARY: In this study, we evaluate the role of bone metabolism biomarkers to help improve the use of radium-223 as therapy for advanced prostate cancer. We found that bone alkaline phosphatase may be a suitable tool.

Starting a robotic thoracic surgery program: From wedge resection to sleeve lobectomy in six months. Initial conclusions.

INTRODUCTION: Robot-assisted thoracic surgery (RATS) is a rapidly expanding technique. In our study, we aimed to analyze the results of the process to adopt robotic surgery in our Department of Thoracic Surgery. METHODS: This is an intention-to-treat analysis of a series of consecutive patients operated on using the RATS approach in our hospital from January 2021 to March 2022. Data were registered for patient characteristics, type of surgery, operative times, conversion rate, chest tube duration, length of hospital stay and complications. The IBM SPSS® statistical software was used for the statistical analysis. A cumulative sum analysis of the operating time was performed to define the learning curve. RESULTS: During the study period, 51 patients underwent robotic surgery, including pulmonary and non-pulmonary interventions. In addition, 15 patients (29.4%) underwent non-pulmonary interventions: one pleural (2%), 2 diaphragmatic (3.9%), and 12 mediastinal (23.5%). Among the mediastinal surgeries, one conversion was necessary (8.3%) for a complex vascular malformation, and 11 were completed by RATS, including 7 (58.3%) thymomas, 3 (25%) pleuro-pericardial cysts, and one (8.3%) neurogenic tumor. Mean operative time was 141 min (104-178), mean chest tube duration was 0.9 days (0-2), and mean length of stay was 1.45 days (1-2). Thirty-six patients underwent lung surgery (70.6%). The complete RATS resections (34; 94.4%) included: 3 wedge resections (11.1%), 2 segmentectomies (3.7%), 28 lobectomies (81.5%), and one sleeve lobectomy (3.7%). Mean surgery time was 194.56 min (141-247), chest tube duration was 3.92 days (1-8), and length of stay was 4.6 days (1-8). Complications occurred in 4 patients (11.1%). No 90-day mortalities were registered. CONCLUSIONS: The implementation of RATS was achieved with good clinical results and operative times for all indications. A rapid learning curve was accomplished in short time. Previous VATS experience, patient selection, team training and program continuity are fundamental to successfully develop a RATS program.

Adjuvant dabrafenib and trametinib for patients with resected BRAF -mutated melanoma: DESCRIBE-AD real-world retrospective observational study.

BRAF and MEK inhibitor, dabrafenib plus trametinib, adjuvant therapy is effective for high-risk resected melanoma patients with BRAF - V600 mutations. However, real-world evidence is limited. We aimed to determine the feasibility of this therapy in routine clinical practice. DESCRIBE-AD, a retrospective observational study, collected real-world data from 25 hospitals in Spain. Histologically confirmed and resected BRAF -mutated melanoma patients aged ≥18 years who were previously treated with dabrafenib plus trametinib adjuvant therapy, were included. The primary objectives were treatment discontinuation rate and time to discontinuation. The secondary objectives included safety and efficacy. From October 2020 to March 2021, 65 patients were included. Dabrafenib and trametinib discontinuation rate due to treatment-related adverse events (TRAEs) of any grade was 9%. Other reasons for discontinuation included patients' decisions (6%), physician decisions (6%), unrelated adverse events (3%), disease progression (5%), and others (5%). The median time to treatment discontinuation was 9 months [95% confidence interval (CI), 5-11]. G3-4 TRAEs occurred in 21.5% of patients, the most common being pyrexia (3%), asthenia (3%), and diarrhoea (3%). Unscheduled hospitalisations and clinical tests occurred in 6 and 22% of patients, respectively. After 20-month median follow-up (95% CI, 18-22), 9% of patients had exitus due to disease progression, with a 12-month relapse-free survival and overall survival rates of 95.3% and 100%, respectively. Dabrafenib and trametinib adjuvant therapy proved effective for melanoma patients in a real-world setting, with a manageable toxicity profile. Toxicity frequencies were low leading to low incidence of unscheduled medical visits, tests, and treatment discontinuations.

Impact of concurrent tumour events on the prostate cancer outcomes of germline BRCA2 mutation carriers.

BACKGROUND: Several studies have reported the association of germline BRCA2 (gBRCA2) mutations with poor clinical outcomes in prostate cancer (PCa), but the impact of concurrent somatic events on gBRCA2 carriers survival and disease progression is unknown. PATIENTS AND METHODS: To ascertain the role of frequent somatic genomic alterations and histology subtypes in the outcomes of gBRCA2 mutation carriers and non-carriers, we correlated the tumour characteristics and clinical outcomes of 73 gBRCA2 and 127 non-carriers. Fluorescent in-situ hybridisation and next-generation sequencing were used to detect copy number variations in BRCA2, RB1, MYC and PTEN. Presence of intraductal and cribriform subtypes was also assessed. The independent impact of these events on cause-specific survival (CSS), metastasis-free survival and time to castration-resistant disease was assessed using cox-regression models. RESULTS: Somatic BRCA2-RB1 co-deletion (41% versus 12%, p < 0.001) and MYC amplification (53.4% versus 18.8%, p < 0.001) were enriched in gBRCA2 compared to sporadic tumours. Median CSS from diagnosis of PCa was 9.1 versus 17.6 years in gBRCA2 carriers and non-carriers, respectively (HR 2.12; p = 0.002), Median CSS in gBRCA2 carriers increased to 11.3 and 13.4 years in the absence of BRCA2-RB1 deletion or MYC amplification, respectively. Median CSS of non-carriers decreased to 8 and 2.6 years if BRCA2-RB1 deletion or MYC amplification were detected. CONCLUSIONS: gBRCA2-related prostate tumours are enriched for aggressive genomic features, such as BRCA2-RB1 co-deletion and MYC amplification. The presence or absence of these events modify the outcomes of gBRCA2 carriers.

Darolutamide Maintenance in Patients With Metastatic Castration-Resistant Prostate Cancer With Nonprogressive Disease After Taxane Treatment (SAKK 08/16).

PURPOSE: To assess the efficacy and safety of darolutamide maintenance after successful taxane chemotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Swiss Group for Clinical Cancer Research (SAKK) 08/16 is a randomized phase II study. Patients with mCRPC who received prior androgen-receptor pathway inhibitors (ARPIs) and subsequently had nonprogressive disease on a taxane were randomly assigned to darolutamide 600 mg twice a day or placebo twice a day. The primary end point was radiographic progression-free survival (rPFS) at 12 weeks. Secondary end points were rPFS, event-free survival, overall survival (OS), prostate-specific antigen (PSA) 50% response rate, and adverse events. RESULTS: Overall, 92 patients were recruited by 26 centers. Prior taxane was docetaxel in 93% and cabazitaxel in 7%. Prior ARPI was abiraterone in 60%, enzalutamide in 31%, and both in 9%. rPFS at 12 weeks was significantly improved with darolutamide (64.7% v 52.2%; P = .127). Median rPFS on darolutamide was 5.5 versus 4.5 months on placebo (hazard ratio [HR], 0.54 [95% CI, 0.32 to 0.91]; P = .017), and median event-free survival was 5.4 versus 2.9 months (HR, 0.46 [95% CI, 0.29 to 0.73]; P = .001). PSA 50% response rate was improved (22% v 4%; P = .014). Median OS for darolutamide was 24 versus 21.3 months for placebo (HR, 0.62 [95% CI, 0.3 to 1.26]; P = .181). Treatment-related adverse events were similar in both arms. CONCLUSION: SAKK 08/16 met its primary end point, showing that switch maintenance with darolutamide after prior taxane chemotherapy and at least one ARPI resulted in a statistically significant but clinically modest rPFS prolongation with good tolerability. The median OS with darolutamide maintenance appears promising. Should these findings be confirmed in a larger trial, maintenance treatment could be a novel strategy in managing patients with mCRPC, especially those who responded well to prior ARPI.

Identification of HMGA2 as a predictive biomarker of response to bintrafusp alfa in a phase 1 trial in patients with advanced triple-negative breast cancer.

Background: We report the clinical activity, safety, and identification of a predictive biomarker for bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGFßRII (a TGF-ß "trap") fused to a human IgG1 mAb blocking PD-L1, in patients with advanced triple-negative breast cancer (TNBC). Methods: In this expansion cohort of a global phase 1 study, patients with pretreated, advanced TNBC received bintrafusp alfa 1200 mg every 2 weeks intravenously until disease progression, unacceptable toxicity, or withdrawal. The primary objective was confirmed best overall response by RECIST 1.1 assessed per independent review committee (IRC). Results: As of May 15, 2020, a total of 33 patients had received bintrafusp alfa, for a median of 6.0 (range, 2.0-48.1) weeks. The objective response rate was 9.1% (95% CI, 1.9%-24.3%) by IRC and investigator assessment. The median progression-free survival per IRC was 1.3 (95% CI, 1.2-1.4) months, and median overall survival was 7.7 (95% CI, 2.1-10.9) months. Twenty-five patients (75.8%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 5 patients (15.2%); no patients had a grade 4 TRAE. There was 1 treatment-related death (dyspnea, hemolysis, and thrombocytopenia in a patient with extensive disease at trial entry). Responses occurred independently of PD-L1 expression, and tumor RNAseq data identified HMGA2 as a potential biomarker of response. Conclusions: Bintrafusp alfa showed clinical activity and manageable safety in patients with heavily pretreated advanced TNBC. HMGA2 was identified as a potential predictive biomarker of response. ClinicalTrialsgov identifier: NCT02517398.

Preoperative localization of lung nodules: a comparative analysis of hookwire and radio-guided procedures.

Background: Histological diagnosis of pulmonary nodules requires surgical resection on many occasions. There are multiple localization strategies each with their own benefits and complications. The objective of this study is to compare preoperative lung nodule localization with hookwire and radiotracer injection (radioguided occult lesion localization, ROLL). To compare results, complications, and volume of the sample resected with both techniques. Methods: Patients undergoing resection of pulmonary nodules with video-assisted thoracoscopy and pre-surgical localization with hookwire or ROLL were studied. Eighty-eight pulmonary nodules were resected in 76 patients: 52 with a hook wire and 36 with a radiotracer. The localization rate, the shortest distance between the nodule and the pleura, the intrapulmonary distance of the locator, the complications, the volume of the resection piece, and the histological result were all assessed. In addition, the factors that influence the volume of the surgical piece were analyzed. Results: All the nodules were resected with both techniques. The intrapulmonary path of the locator is longer for the ROLL group (23.91 vs. 16.28 mm; P=0.04), with no differences in the distance from the nodule to the pleura. The rate of pneumothorax was significantly higher after the placement of a hook wire (69.2% vs. 24.2%; P<0.0001), while there were no differences in the presence of hemorrhage. The volume of the pieces resected using ROLL was more minor than with hookwire, although not statistically significant (20.19 vs. 34.26 cc; P=0.07). Conclusions: Preoperative localization with the ROLL technique is safer than the placement of hookwire. In addition, the ROLL technique shows a tendency to obtain a smaller volume of resected tissue since the marking is not affected by the intrapulmonary route used during marker placement. ROLL technique allows to locate lung nodules with fewer complications than hookwire and probably gets smaller resection samples.

Update in collecting duct carcinoma: Current aspects of the clinical and molecular characterization of an orphan disease.

Collecting duct renal cell carcinoma (cdRCC), which until recently was thought to arise from the collecting ducts of Bellini in the renal medulla, is a rare and aggressive type of non-clear renal cell carcinoma (ncRCC), accounting for 1% of all renal tumors and with nearly 50% of patients being diagnosed with Stage IV disease. The median overall survival in this setting is less than 12 months. Several regimens of chemotherapies had been used based on morphologic and cytogenetic similarities with urothelial cell carcinoma described previously, although the prognosis still remains poor. The use of targeted therapies also did not result in favorable outcomes. Recent works using NGS have highlighted genomic alterations in SETD2, CDKN2A, SMARCB1, and NF2. Moreover, transcriptomic studies have confirmed the differences between urothelial carcinoma and cdRCC, the possible true origin of this disease in the distal convoluted tubule (DCT), differentiating from other RCC (e.g., clear cell and papillary) that derive from the proximal convoluted tubule (PCT), and enrichment in immune cells that may harbor insights in novel treatment strategies with immunotherapy and target agents. In this review, we update the current aspects of the clinical, molecular characterization, and new targeted therapeutic options for Collecting duct carcinoma and highlight the future perspectives of treatment in this setting.

Characterization of the MicroRNA Cargo of Extracellular Vesicles Isolated from a Pulmonary Tumor-Draining Vein Identifies miR-203a-3p as a Relapse Biomarker for Resected Non-Small Cell Lung Cancer.

In resected non-small cell lung cancer (NSCLC), post-surgical recurrence occurs in around 40% of patients, highlighting the necessity to identify relapse biomarkers. An analysis of the extracellular vesicle (EV) cargo from a pulmonary tumor-draining vein (TDV) can grant biomarker identification. We studied the pulmonary TDV EV-miRNAome to identify relapse biomarkers in a two-phase study (screening and validation). In the screening phase, a 17-miRNA relapse signature was identified in 18 selected patients by small RNAseq. The most expressed miRNA from the signature (EV-miR-203a-3p) was chosen for further validation. Pulmonary TDV EV-miR-203a-3p was studied by qRT-PCR in a validation cohort of 70 patients, where it was found to be upregulated in relapsed patients (p = 0.0194) and in patients with cancer spread to nearby lymph nodes (N+ patients) (p = 0.0396). The ROC curve analysis showed that TDV EV-miR-203a-3p was able to predict relapses with a sensitivity of 88% (AUC: 0.67; p = 0.022). Moreover, patients with high TDV EV-miR-203a-3p had a shorter time to relapse than patients with low levels (43.6 vs. 97.6 months; p = 0.00703). The multivariate analysis showed that EV-miR-203a-3p was an independent, predictive and prognostic post-surgical relapse biomarker. In conclusion, pulmonary TDV EV-miR-203a-3p is a promising new relapse biomarker for resected NSCLC patients.

Treatment and intention-to-treat propensity score analysis to evaluate the impact of video-assisted thoracic surgery on 90-day mortality after anatomical resection for lung cancer.

OBJECTIVES: The aim of this study was to know the treatment effect of video-assisted thoracic surgery (VATS) on 90-day mortality after anatomical lung resection based on a nationwide cohort. METHODS: This is a multicentre prospective cohort of 2721 anatomical resections for lung cancer from December 2016 to March 2018. Treatment and intention-to-treat (ITT) analyses were performed after inverse probability score weighting and different propensity score matching algorithms. Covariate balance was assessed by standardized mean differences. The estimators reported were the average treatment effect, the average treatment effect on the treated and odds ratios after conditional logistic models with 95% confidence intervals. The unconfoundedness assumption was evaluated by sensitivity analysis for average treatment effect (c-dependence) and average treatment effect on the treated (Γ). RESULTS: VATS was the initial approach in 1911 patients (70.2%), though 273 cases (14.3%) had to be converted to thoracotomy. Ninety-day mortality rates were: treatment analysis (VATS 1.16% vs open 3.9%, P < 0.001), ITT analysis (VATS 1.78% vs open 3.36%, P = 0.012). After inverse probability score weighting and propensity score matching, in the treatment analysis, VATS meant absolute risk reductions between 2.25% and 2.96% and relative risk reductions between 65% and 70% [OR = 0.34 (95% confidence interval 0.15-0.79), all P-values <0.004). However, all the estimators turned out to be non-significant in the ITT analyses. A high sensitivity to unobservable confounders was proved (c-dependence 0.135, Γ = 1.5). CONCLUSIONS: VATS can reduce the risk of 90-day mortality after anatomical lung resection. However, the implications of conversion to thoracotomy, comparing ITT versus treatment analysis, and the potential impact of hidden bias should deserve further attention in the future.

Surgeon preimplantation macroscopic graft appraisal improves risk stratification of deceased kidney donors: a prospective study.

BACKGROUND: Preimplantation scores assist with correct kidney graft allocation, but macroscopic graft features have never been evaluated in this scenario. METHODS: We designed a graft appraisal questionnaire, assessed its reproducibility by comparing the senior and junior surgeon responses and evaluated which features can predict transplant outcomes in 202 patients transplanted from 144 donors at a tertiary center. We created new prediction models in combination with validated preimplantation scores. The primary outcome was graft loss or eGFR<30 mL/min/1.73 m2 at six months and secondary outcomes were delayed graft function, early graft loss and graft function at six months. RESULTS: Interrater correlation was very good for adherent perinephric fat (kappa=0.91) and acceptable for cortical surface roughness (kappa=0.51) and cortical color (kappa=0.47). Adherent perirenal fat (Odds ratio=4.77; 95% CI: 2.10-10.85) and surface roughness (OR=2.11, 95% CI: 1.25-3.58) were independent predictors of the primary outcome, improving the kidney donor risk index efficacy model (AUC 0.71 vs. 0.82, P≤0.001), while cortical color and adherent fat improved the Irish risk model for delayed graft function (AUC 0.76 vs. 0.82, P=0.03). We created nomograms to visually assess the risk of both endpoints. CONCLUSIONS: Kidney graft macroscopic appraisal is reproducible between surgeons and can improve the accuracy of clinical preimplantational prediction scores.

Surgical Risk Following Anatomic Lung Resection in Thoracic Surgery: A Prediction Model Derived from a Spanish Multicenter Database. / Riesgo quirúrgico tras resección pulmonar anatómica en cirugía torácica. Modelo predictivo a partir de una base de datos nacional multicéntrica.

INTRODUCTION: The aim of this study was to develop a surgical risk prediction model in patients undergoing anatomic lung resections from the registry of the Spanish Video-Assisted Thoracic Surgery Group (GEVATS). METHODS: Data were collected from 3,533 patients undergoing anatomic lung resection for any diagnosis between December 20, 2016 and March 20, 2018. We defined a combined outcome variable: death or Clavien Dindo grade IV complication at 90 days after surgery. Univariate and multivariate analyses were performed by logistic regression. Internal validation of the model was performed using resampling techniques. RESULTS: The incidence of the outcome variable was 4.29% (95% CI 3.6-4.9). The variables remaining in the final logistic model were: age, sex, previous lung cancer resection, dyspnea (mMRC), right pneumonectomy, and ppo DLCO. The performance parameters of the model adjusted by resampling were: C-statistic 0.712 (95% CI 0.648-0.750), Brier score 0.042 and bootstrap shrinkage 0.854. CONCLUSIONS: The risk prediction model obtained from the GEVATS database is a simple, valid, and reliable model that is a useful tool for establishing the risk of a patient undergoing anatomic lung resection.

Acute kidney injury as a risk factor for mortality in oncological patients receiving checkpoint inhibitors.

BACKGROUND: Checkpoint inhibitors (CPIs) have drastically improved metastatic cancer outcomes. However, immunotherapy is associated with multiple toxicities, including acute kidney injury (AKI). Data about CPI-related AKI are limited. Our aim was to determine risk factors for CPI-related AKI as well as its clinical characteristics and its impact on mortality in patients undergoing immunotherapy. METHODS: All patients under CPI at our centre between March 2018 and May 2019 and with a follow-up through April 2020 were included. Demographic, clinical and laboratory data were collected. AKI was defined according to the Kidney Disease: Improving Global Outcomes guidelines. We performed a logistic regression model to identify independent risk factors for AKI and actuarial survival analysis to establish risk factors for mortality in this population. RESULTS: A total of 759 patients were included, with a median age of 64 years. A total of 59% were men and baseline median creatinine was 0.80 mg/dL. The most frequent malignancy was lung cancer and 56% were receiving anti-programmed death protein 1 (PD-1). About 15.5% developed AKI during the follow-up. Age and baseline kidney function were identified as independent risk factors for CPI-related AKI. At the end of follow-up, 52.3% of patients had died. The type of cancer (not melanoma, lung or urogenital malignance), type of CPI (not cytotoxic T-lymphocyte-associated protein 4, PD-1, programmed death-ligand 1 or their combination) and the presence of an episode of AKI were identified as risk factors for mortality. CONCLUSIONS: A total of 15.5% of patients under immunotherapy presented with AKI. A single AKI episode was identified as an independent risk factor for mortality in these patients and age and baseline renal function were risk factors for the development of AKI.

Pathological response to neoadjuvant therapy with chemotherapy vs chemoradiotherapy in stage III NSCLC-contribution of IASLC recommendations.

BACKGROUND: Neoadjuvant treatment (NT) with chemotherapy (Ch) is a standard option for resectable stage III (N2) NSCLC. Several studies have suggested benefits with the addition of radiotherapy (RT) to NT Ch. The International Association for the Study of Lung Cancer (IASLC) published recommendations for the pathological response (PHR) of NSCLC resection specimens after NT. AIM: To contribute to the IASLC recommendations showing our results of PHR to NT Ch vs NT chemoradiotherapy (ChRT). METHODS: We analyzed 67 consecutive patients with resectable stage III NSCLC with positive mediastinal nodes treated with surgery after NT Ch or NT ChRT between 2013 and 2020. After NT, all patients were evaluated for radiological response (RR) according to Response Evaluation Criteria in Solid Tumours criteria and evaluated for surgery by a specialized group of thoracic surgeons. All histological samples were examined by the same two pathologists. PHR was evaluated by the percentage of viable cells in the tumor and the resected lymph nodes. RESULTS: Forty patients underwent NT ChRT and 27 NT Ch. Fifty-six (83.6%) patients underwent surgery (35 ChRT and 21 Ch). The median time from ChRT to surgery was 6 wk (3-19) and 8 wk (3-21) for Ch patients. We observed significant differences in RR, with disease progression in 2.5% and 14.8% of patients with ChRT and Ch, respectively, and partial response in 62.5% ChRT vs 29.6% Ch (P = 0.025). In PHR we observed ≤ 10% viable cells in the tumor in 19 (54.4%) and 2 cases (9.5%), and in the resected lymph nodes (RLN) 30 (85.7%) and 7 (33.3%) in ChRT and Ch, respectively (P = 0.001). Downstaging was greater in the ChRT compared to the Ch group (80% vs 33.3%; P = 0.002). In the univariate analysis, NT ChRT had a significant impact on partial RR [odds ratio (OR) 12.5; 95% confidence interval (CI): 1.21 - 128.61; P = 0.034], a decreased risk of persistence of cancer cells in the tumor and RLN and an 87.5% increased probability for achieving downstaging (OR 8; 95%CI: 2.34-27.32; P = 0.001). CONCLUSION: We found significant benefits in RR and PHR by adding RT to Ch as NT. A longer follow-up is necessary to assess the impact on clinical outcomes.

Optimal Sequencing and Predictive Biomarkers in Patients with Advanced Prostate Cancer.

The treatment landscape of advanced prostate cancer has completely changed during the last decades. Chemotherapy (docetaxel, cabazitaxel), androgen-receptor signaling inhibitors (ARSi) (abiraterone acetate, enzalutamide), and radium-223 have revolutionized the management of metastatic castration-resistant prostate cancer (mCRPC). Lutetium-177-PSMA-617 is also going to become another treatment option for these patients. In addition, docetaxel, abiraterone acetate, apalutamide, enzalutamide, and radiotherapy to primary tumor have demonstrated the ability to significantly prolong the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Finally, apalutamide, enzalutamide, and darolutamide have recently provided impactful data in patients with nonmetastatic castration-resistant disease (nmCRPC). However, which is the best treatment sequence for patients with advanced prostate cancer? This comprehensive review aims at discussing the available literature data to identify the optimal sequencing approaches in patients with prostate cancer at different disease stages. Our work also highlights the potential impact of predictive biomarkers in treatment sequencing and exploring the role of specific agents (i.e., olaparib, rucaparib, talazoparib, niraparib, and ipatasertib) in biomarker-selected populations of patients with prostate cancer (i.e., those harboring alterations in DNA damage and response genes or PTEN).

Prognostic Score and Benefit from Abiraterone in First-line Metastatic, Castration-resistant Prostate Cancer.

BACKGROUND: Most available prognostic nomograms in metastatic castration-resistant prostate cancer (mCRPC) are derived from datasets not representative of the current treatment landscape. A prognostic nomogram for first-line mCRPC treatment was developed from patients treated in the PREVAIL study. OBJECTIVE: To validate the Armstrong model in the COU-AA-302 trial. DESIGN, SETTING, AND PARTICIPANTS: A post hoc analysis of mCRPC patients treated in the COU-AA-302 trial was carried out (NCT00887198). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The Armstrong prognostic model was applied to patients treated in COU-AA-302. A continuous risk score was derived from coefficients from the original model. Time-dependent area under the curve (tAUC) was used to evaluate the overall predictive ability of the model. Patients were categorized according to the number of risk factors present into those at a low (three or fewer risk factors), intermediate (four to six risk factors), and high (seven to ten risk factors) risk. The association with survival was assessed with Cox regression models. Interaction tests were used to assess the impact of treatment arm in each of the prognostic groups. RESULTS AND LIMITATIONS: A total of 1088 patients were analyzed. The risk score was associated with overall survival (OS; tAUC 0.733). Most patients were at a low (49%) or intermediate (41%) risk. Risk category was significantly associated with OS (hazard ratio [HR]: 2.3; 95% confidence interval [CI]: 1.9-2.4; p < 0.001), radiographic progression-free survival (rPFS; HR: 1.7; 95% CI: 1.5-1.8; p < 0.001), and prostate-specific antigen progression-free survival (HR: 1.7; 95% CI: 1.5-1.9; p < 0.001). A significant interaction between risk group and OS (p = 0.007) and rPFS (p = 0.009) was observed. Survival was superior in low-risk patients (HR: 0.73; 95% CI: 0.59-0.89; p = 0.009), but similar in intermediate-risk (HR: 0.97; 95% CI: 0.79-1.21; p = 0.9) and high-risk (HR: 1.35; 95% CI: 0.80-2.28; p = 0.5) patients. Two-year OS rates in abiraterone versus placebo were 82% versus 74% in low-risk, 55% versus 52% in intermediate-risk, and 28% versus 31% in high-risk patients. CONCLUSIONS: We validate the prognostic value of the Armstrong risk model in patients treated with first-line androgen receptor signaling inhibitors. Abiraterone provided a greater benefit in low-risk patients with less aggressive disease. Further research is needed to establish the role of Armstrong risk groups for treatment selection in mCRPC patients. PATIENT SUMMARY: In this report, we validated the Armstrong nomogram in the COU-AA-302 trial population. We found a similar prognostic performance to that of the original model. Good-risk patients received the greatest benefit from abiraterone.