Development and validation of a self-attention network-based algorithm to detect mediastinal lesions on computed tomography images.

Background: Diagnosis of mediastinal lesions on computed tomography (CT) images is challenging for radiologists, as numerous conditions can present as mass-like lesions at this site. This study aimed to develop a self-attention network-based algorithm to detect mediastinal lesions on CT images and to evaluate its efficacy in lesion detection. Methods: In this study, two separate large-scale open datasets [National Institutes of Health (NIH) DeepLesion and Medical Image Computing and Computer Assisted Intervention (MICCAI) 2022 Mediastinal Lesion Analysis (MELA) Challenge] were collected to develop a self-attention network-based algorithm for mediastinal lesion detection. We enrolled 921 abnormal CT images from the NIH DeepLesion dataset into the pretraining stage and 880 abnormal CT images from the MELA Challenge dataset into the model training and validation stages in a ratio of 8:2 at the patient level. The average precision (AP) and confidence score on lesion detection were evaluated in the validation set. Sensitivity to lesion detection was compared between the faster region-based convolutional neural network (R-CNN) model and the proposed model. Results: The proposed model achieved an 89.3% AP score in mediastinal lesion detection and could identify comparably large lesions with a high confidence score >0.8. Moreover, the proposed model achieved a performance boost of almost 2% in the competition performance metric (CPM) compared to the faster R-CNN model. In addition, the proposed model can ensure an outstanding sensitivity with a relatively low false-positive rate by setting appropriate threshold values. Conclusions: The proposed model showed excellent performance in detecting mediastinal lesions on CT. Thus, it can drastically reduce radiologists' workload, improve their performance, and speed up the reporting time in everyday clinical practice.

Advances in Immunotherapy for Malignant Pleural Mesothelioma: From Emerging Strategies to Translational Insights.

MPM stands as a rare malignancy necessitating improved therapeutic strategies due to its limited treatment choices and unfavorable prognosis. The advent of immune checkpoint inhibitors has heralded a paradigm shift in the therapeutic landscape of MPM, offering promising avenues across diverse clinical scenarios. In the context of advanced stages of the disease, Immune check-point inhibitors targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-as-sociated protein 4 (CTLA-4), have exhibited encouraging potential in clinical trials, particularly manifesting efficacy among patients exhibiting disease progression following chemotherapy regimens. Innovative combination regimens, exemplified by the concurrent administration of nivolumab and ipilimumab, have demonstrated marked improvement in survival and patient's benefits. A deeper comprehension of the intricate genetic underpinnings of MPM, encompassing key mutations such as cyclin-dependent kinase inhibitor 2A (CDKN2A), neurofibromin 2 (NF2), and BRCA1-associated protein 1 (BAP1) mutations, has elucidated novel avenues for targeted therapeutic interventions. This review accentuates the transformative capacity of immunotherapy in revolutionizing the therapeutic outlook for MPM, thereby potentially translating into augmented survival rates and offering glimpses of new approaches on the horizon. Despite the persisting challenges, the synergistic crossroads of interdisciplinary research and collaborative clinical endeavors portend a hopeful landscape for MPM treatment.

El mesotelioma pleural maligno (MPM) es una neoplasia poco frecuente que requiere una mejora de las estrategias terapéuticas debido a sus limitadas opciones de tratamiento y a su pronóstico desfavorable. La llegada de los inhibidores de los puntos de control inmunitario ha supuesto un cambio de paradigma en el panorama terapéutico del MPM, ofreciendo vías prometedoras en diversos escenarios clínicos. En el contexto de los estadios avanzados de la enfermedad, los inhibidores de puntos de control inmunitario dirigidos contra la proteína de muerte celular programada 1 (PD-1) y la proteína 4 asociada a los linfocitos T citotóxicos (CTLA-4) han mostrado un potencial alentador en los ensayos clínicos, sobre todo por su eficacia en los pacientes con progresión de la enfermedad tras los regímenes de quimioterapia. Los regímenes combinados innovadores, ejemplificados por la administración concurrente de nivolumab e ipilimumab, han demostrado una mejora significativa de la supervivencia y de los beneficios para los pacientes. Una comprensión más profunda de los complejos fundamentos genéticos del MPM, que abarca mutaciones clave como el inhibidor de la cinasa dependiente de ciclina 2A (CDKN2A), la neurofibromina 2 (NF2) y las mutaciones de la proteína 1 asociada a BRCA1 (BAP1), ha dilucidado nuevas vías para el desarrollo de intervenciones terapéuticas dirigidas. Esta revisión acentúa la capacidad transformadora de la inmunoterapia para revolucionar las perspectivas terapéuticas en el MPM, lo que podría traducirse en un aumento de las tasas de supervivencia y ofrecer nuevos enfoques terapéuticos en el horizonte próximo. A pesar de los retos persistentes, el cruce sinérgico de la investigación interdisciplinar y los esfuerzos clínicos de colaboración auguran un panorama esperanzador en el tratamiento de los MPM.

Outcomes of Surgery for Metachronous Second Primary Non-small Cell Lung Cancer

Objective: The optimal surgical approach for second primary metachronous lung cancer (MPLC) remains unclear. Our aim is to evaluate the morbidity and prognostic value based on the extent of surgical resection in MPLC. Methods: Retrospective study of 84 patients with a history of anatomical resection for lung cancer and MPLC surgically treated between January 2010 and December 2020. Results: The interval between the initial primary tumor and the second was 50.38±32.89 months. The second resection was contralateral in 43 patients (51.2%) and ipsilateral in 41 (48.8%). Thirty-six patients (42.9%) underwent a second anatomical resection, and in 48 patients (57.1%), it was non-anatomical. Postoperative complications were observed in 29 patients (34.5%) after the second lung resection. According to the Clavien-Dindo classification, 95.2% were mild (Clavien-Dindo I–II), and a single patient died (1.2%) in the postoperative period (Grade V). Prolonged air leak (p=0.037), postoperative arrhythmias (p=0.019) and hospital stay showed significant differences depending on the extent of surgery in ipsilateral resections. The main histological type was adenocarcinoma (47.6%) and the median tumor size was 17.74±11.74mm. The overall survival was 58.07 months (95% CI 49.29–66.85) for patients undergoing anatomical resection and 50.97 months (95% CI 43.31–58.63) for non-anatomical without significant differences (p=0.144). The disease-free survival after the second surgery was 53.75 months (95% CI 45.28–62.23) for anatomical resection and 41.34 months (95% CI 33.04–49.65) for non-anatomical group. Conclusion: Second anatomical resections provide good long-term outcomes and have been shown to provide better disease-free survival compared to non-anatomical resections in properly selected patients. (AU)

[Questions and Answers in Lung Cancer]. / Preguntas y respuestas en cáncer de pulmón.

Over the past 2 decades, scientific evidence has strongly supported the use of low-radiation dose chest computed tomography (CT) as a screening technique for lung cancer. This approach has resulted in a significant reduction in mortality rates by enabling the detection of early-stage lung cancer amenable to potentially curative treatments. Regarding diagnosis, there are also novel methods under study, such as liquid biopsy, identification of the pulmonary microbiome, and the use of artificial intelligence techniques, which will play a key role in the near future. At present, there is a growing trend towards less invasive surgical procedures, such as segmentectomy, as an alternative to lobectomy. This procedure is based on 2 recent clinical trials conducted on peripheral tumors measuring less than 2 cm. Although these approaches have demonstrated comparable survival rates, there remains controversy due to uncertainties surrounding recurrence rates and functional capacity preservation. With regard to adjuvant therapy, immunotherapy, either as a monotherapy or in conjunction with chemotherapy, has shown encouraging results in resectable stages of locally advanced lung cancer, demonstrating complete pathologic responses and improved overall survival.After surgery treatment, despite the lack of solid evidence for long-term follow-up of these patients, clinical practice recommends periodic CT scans during the early years.In conclusion, there have been significant advances in lung cancer that have improved diagnostic techniques using new technologies and screening programs. Furthermore, the treatment of lung cancer is increasingly personalized, resulting in an improvement in the survival of patients.

Outcomes of Surgery for Metachronous Second Primary Non-small Cell Lung Cancer.

OBJECTIVE: The optimal surgical approach for second primary metachronous lung cancer (MPLC) remains unclear. Our aim is to evaluate the morbidity and prognostic value based on the extent of surgical resection in MPLC. METHODS: Retrospective study of 84 patients with a history of anatomical resection for lung cancer and MPLC surgically treated between January 2010 and December 2020. RESULTS: The interval between the initial primary tumor and the second was 50.38±32.89 months. The second resection was contralateral in 43 patients (51.2%) and ipsilateral in 41 (48.8%). Thirty-six patients (42.9%) underwent a second anatomical resection, and in 48 patients (57.1%), it was non-anatomical. Postoperative complications were observed in 29 patients (34.5%) after the second lung resection. According to the Clavien-Dindo classification, 95.2% were mild (Clavien-Dindo I-II), and a single patient died (1.2%) in the postoperative period (Grade V). Prolonged air leak (p=0.037), postoperative arrhythmias (p=0.019) and hospital stay showed significant differences depending on the extent of surgery in ipsilateral resections. The main histological type was adenocarcinoma (47.6%) and the median tumor size was 17.74±11.74mm. The overall survival was 58.07 months (95% CI 49.29-66.85) for patients undergoing anatomical resection and 50.97 months (95% CI 43.31-58.63) for non-anatomical without significant differences (p=0.144). The disease-free survival after the second surgery was 53.75 months (95% CI 45.28-62.23) for anatomical resection and 41.34 months (95% CI 33.04-49.65) for non-anatomical group. CONCLUSION: Second anatomical resections provide good long-term outcomes and have been shown to provide better disease-free survival compared to non-anatomical resections in properly selected patients.

A proof of concept for matchete: an automated tool for matching effective theories.

Studying the impact of new-physics models on low-energy observables necessitates matching to effective field theories at the relevant mass thresholds. We introduce the first public version of Matchete, a computer tool for matching weakly-coupled models at one-loop order. It uses functional methods to directly compute all matching contributions in a manifestly gauge-covariant manner, while simplification methods eliminate redundant operators from the output. We sketch the workings of the program and provide examples of how to match simple Standard Model extensions. The package, documentation, and example notebooks are publicly available at https://gitlab.com/matchete/matchete.

Acute Leukemia Relapse after Hematopoietic Stem Cell Transplantation: The Good, the Bad, and the Ugly of Isolated Extramedullary Relapse in a Latin American Population.

Hematopoietic stem cell transplantation (HSCT) is an effective therapy for acute leukemia (AL). Relapse represents the main cause of mortality. Isolated extramedullary relapse (iEMR) is atypical and has been related to better outcomes. Here we describe the clinical characteristics and outcomes of AL relapse after HSCT in our study population and analyze the impacts of different types of relapse on survival outcomes. This retrospective, multicenter study included 124 patients age ≥15 years with AL who underwent HSCT between 2004 and 2019. At diagnosis, 66.1% of the patients had lymphocytic AL, 19.7% presented with high-risk features, and 18.5% had extramedullary disease (EMD). At HSCT, 83.1% of the patients were in complete remission (CR), and 44.8% had negative measurable residual disease (MRD). The vast majority of donors were related (96%), including 48.4% HLA-matched and 47.6% haploidentical. Myeloablative conditioning was provided to 80.6% of patients. The median overall survival (OS) was 15 months (95% confidence interval [CI] 9.9 to 20.1 months). Factors associated with improved OS were adolescent and young adult (AYA) patient (P = .035), first or second CR (P = .026), and chronic graft-versus-host disease (GVHD) (P < .001). Acute GVHD grade III-IV (P = .009) was associated with increased mortality. The median relapse-free survival was 13 months (95% CI, 7.17 to 18.8 months); early disease status (P = .017) and chronic GVHD (P < .001) had protective roles. Sixty-eight patients (55%) relapsed after HSCT, with a median time to relapse of 6 months (95% CI, 3.6 to 8.4 months). iEMR was reported in 16 patients (23.5%). The most commonly involved extramedullary sites were the central nervous system and skin. Compared to patients with bone marrow relapse, all patients with iEMR had a diagnosis of acute lymphoid leukemia (P = .008), and 93.8% belonged to the AYA group; regarding pre-HSCT characteristics, iEMR patients had higher rates of negative MRD (P = .06) and a history of EMD (P = .009). Seventy-seven percent of relapsed patients received additional treatment with curative intent. The median OS after relapse (OSr) was 4 months (95% CI, 2.6 to 5.4 months). Factors related to increased OSr included lymphoid phenotype (P = .03), iEMR (P = .0042), late relapse (≥6 months) (P = .014), receipt of systemic therapy including second HSCT (P < .001), and response to therapy (P < .001). Rates of relapse and iEMR were higher than those previously reported in other studies. Advanced disease, reduced-intensity conditioning, and a diminished graft-versus-leukemia effect were factors influencing these findings. At relapse, presenting with iEMR after 6 months and receiving intensive therapy with adequate response were associated with better outcomes. Our results strongly suggest that a personalized approach to treating patients with HSCT is needed to counterbalance specific adverse factors and can positively impact clinical outcomes.