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Simple Summary: This paper discusses the challenges in treating high-grade gliomas, particularly glioblastomas, which are aggressive brain tumors with high recurrence rates. It highlights the limitations of current diagnostic imaging modalities, such as gadolinium-based MRI, in accurately detecting tumor recurrence versus treatment-related changes. The paper explores the emerging role of positron emission tomography (PET) in glioma imaging, especially with the use of radiotracers like PSMA, which can help differentiate between tumor recurrence and treatment effects. Furthermore, the paper reviews the concept of theranostics, which integrates diagnostics and therapy, offering a targeted approach to glioma treatment. It discusses various radioligands, including PSMA, 213Bi-DOTA-substance P, 90Y-DOTATOC, 18F-FDOPA, p-[131I]-iodo-L-phenylalanine, and 18F-GE-180, which have shown promise in diagnosing and treating recurrent gliomas. The potential of theranostics to minimize systemic toxicity and improve treatment outcomes is emphasized. Moreover, the paper highlights the importance of considering quality-of-life (QOL) outcomes in glioma patients, as conventional treatments often have significant impacts on patients' well-being. While theranostics offers a personalized approach to treatment, its potential promise for functional outcomes and QOL needs further investigation. The paper suggests that future research should focus on understanding the broader implications of theranostics on patient well-being, incorporating factors such as demographics, tumor characteristics, and treatment-related effects into QOL assessments. Overall, the paper underscores the potential of theranostics to revolutionize glioma management and improve patient outcomes in the future. Gliomas represent the most commonly occurring tumors in the central nervous system and account for approximately 80% of all malignant primary brain tumors. With a high malignancy and recurrence risk, the prognosis of high-grade gliomas is poor, with a mean survival time of 12–18 months. While contrast-enhanced MRI serves as the standard diagnostic imaging modality for gliomas, it faces limitations in the evaluation of recurrent gliomas, failing to distinguish between treatment-related changes and tumor progression, and offers no direct therapeutic options. Recent advances in imaging modalities have attempted to address some of these limitations, including positron emission tomography (PET), which has demonstrated success in delineating tumor margins and guiding the treatment of recurrent gliomas. Additionally, with the advent of theranostics in nuclear medicine, PET tracers, when combined with therapeutic agents, have also evolved beyond a purely diagnostic modality, serving both diagnostic and therapeutic roles. This review will discuss the growing involvement of theranostics in diagnosing and treating recurrent gliomas and address the associated impact on quality of life and functional recovery. [ABSTRACT FROM AUTHOR]

Simple Summary: Acute promyelocytic leukemia (APL) stands as a remarkable success in achieving high cure rates with chemotherapy-free treatment regimens. Despite these remarkable outcomes, hematologists managing patients with APL take into consideration the distinct side effects associated with the two dual differentiation agents, i.e., all-transretinoic acid (ATRA) and arsenic trioxide (ATO). The objective of this paper is to review relevant literature data and discuss the recommended management strategies of non-hematologic early and late complications that arosein patients diagnosed with APL who were treated with ATO and ATRA-based regimens. The hallmark of acute promyelocytic leukemia (APL) is the presence of the characteristic fusion transcript of the promyelocytic leukemia gene with the retinoic acid receptor α gene (PML::RARA). The PML::RARA fusion is a molecular target for all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Therapies based on ATRA plus ATO have excellent outcomes in terms of complete remission rates, overall survival, and achievement of deep and durable molecular responses with a very low incidence of relapse. However, although the combination of ATRA and ATO has lower hematologic toxicity than standard chemotherapy, its use is associated with a spectrum of distinctive toxicities, such as differentiation syndrome, liver toxicity, QT interval prolongation, and neurotoxicity. Rigorous monitoring of patients' clinical evolution is indispensable for identifying and addressing each complication. The objective is to maintain an equilibrium between treatment-induced adverse events and therapeutic efficacy. This paper focused on non-hematologic complications associated with the combination of ATRA and ATO. Additionally, we discuss late-onset complications of this therapy. In summary, the majority of treatment-related adverse events are manageable, self-limiting, and reversible. More so, there seems to be a lower incidence rate of secondary neoplasms compared to standard chemotherapy. However, further research is required to assess how the ATRA plus ATO regimen affects the emergence of additional comorbidities. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton therapy is a crucial tool for head and neck and skull-base cancers, offering benefits over photon therapy by lowering the risk of adverse effects. However, its full potential could be further explored by better characterizing the uncertainties related to its relative biological effectiveness. Addressing these uncertainties is crucial for maximizing the potential of proton therapy. We explore the significance of proton therapy's biological impact in these cancers, review relative biological effectiveness uncertainties and modeling, and examine clinical outcomes and evidence linking specific biological factors to patient adverse effects. Additionally, we review the current clinical practices and provide insights into innovative developments and their future clinical implementation. Proton therapy has emerged as a crucial tool in the treatment of head and neck and skull-base cancers, offering advantages over photon therapy in terms of decreasing integral dose and reducing acute and late toxicities, such as dysgeusia, feeding tube dependence, xerostomia, secondary malignancies, and neurocognitive dysfunction. Despite its benefits in dose distribution and biological effectiveness, the application of proton therapy is challenged by uncertainties in its relative biological effectiveness (RBE). Overcoming the challenges related to RBE is key to fully realizing proton therapy's potential, which extends beyond its physical dosimetric properties when compared with photon-based therapies. In this paper, we discuss the clinical significance of RBE within treatment volumes and adjacent serial organs at risk in the management of head and neck and skull-base tumors. We review proton RBE uncertainties and its modeling and explore clinical outcomes. Additionally, we highlight technological advancements and innovations in plan optimization and treatment delivery, including linear energy transfer/RBE optimizations and the development of spot-scanning proton arc therapy. These advancements show promise in harnessing the full capabilities of proton therapy from an academic standpoint, further technological innovations and clinical outcome studies, however, are needed for their integration into routine clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer in all its forms of expression is a major cause of death. The bladder cancer is also causes the same. finding the biomarkers responsible for the cancer is a challenging task and in certain cases, such as disease progression and therapy response, it become more challenging. The advancements in technology provides latest machine learning methods that help to identify the genomic biomarkers computationally. In this paper, the genomic biomarkers are tracked for bladder cancer from Univeristy of Calgary cohort and different bioinformatics methods, such as differential gene expression, survival rate estimation, consensus gene selection approaches were optimally used. The elastic-net based regression method has been utilized as a machine learning method which shows satisfactory results. Cancer in all its forms of expression is a major cause of death. To identify the genomic reason behind cancer, discovery of biomarkers is needed. In this paper, genomic data of bladder cancer are examined for the purpose of biomarker discovery. Genomic biomarkers are indicators stemming from the study of the genome, either at a very low level based on the genome sequence itself, or more abstractly such as measuring the level of gene expression for different disease groups. The latter method is pivotal for this work, since the available datasets consist of RNA sequencing data, transformed to gene expression levels, as well as data on a multitude of clinical indicators. Based on this, various methods are utilized such as statistical modeling via logistic regression and regularization techniques (elastic-net), clustering, survival analysis through Kaplan–Meier curves, and heatmaps for the experiments leading to biomarker discovery. The experiments have led to the discovery of two gene signatures capable of predicting therapy response and disease progression with considerable accuracy for bladder cancer patients which correlates well with clinical indicators such as Therapy Response and T-Stage at surgery with Disease Progression in a time-to-event manner. [ABSTRACT FROM AUTHOR]

Simple Summary: Completion lobectomy (CL) entails the resection of the remaining pulmonary lobe subsequent to wedge resection or segmentectomy. Indications for CL include reoperations for multiple or relapsed lung cancers and metastatic lung tumors, and the prognostic advantage of these procedures has been widely reported. However, ipsilateral surgical treatments, particularly within the same lobe, present challenges due to the development of intrapleural adhesions, rendering reoperation more difficult and time-consuming. VATS has emerged as the gold standard in the surgical treatment of early-stage NSCLC, offering superior postoperative outcomes when compared to thoracotomy. Its efficacy has been well established, even during complex procedures. However, its application in ipsilateral reoperations remains anecdotal, and to the best of our knowledge, no studies have analyzed the safety and efficacy of uniportal-VATS in this setting. This paper aims to evaluate the role of iniportal-VATS in CL long after wedge resection or anatomical segmentectomy in the same lobe. Background: Completion lobectomy (CL) following a prior resection in the same lobe may be complicated by severe pleural or hilar adhesions. The role of uniportal video-assisted thoracoscopic surgery (U-VATS) has never been evaluated in this setting. Methods: Data were collected from two Italian centers. Between 2015 and 2022, 122 patients (60 men and 62 women, median age 67.7 ± 8.913) underwent U-VATS CL at least 4 weeks after previous lung surgery. Results: Twenty-eight (22.9%) patients were affected by chronic obstructive pulmonary disease (COPD) and twenty-five (20.4%) were active smokers. Among the cohort, the initial surgery was performed using U-VATS in 103 (84.4%) patients, triportal-VATS in 8 (6.6%), and thoracotomy in 11 (9.0%). Anatomical segmentectomy was the initial surgery in 46 (37.7%) patients, while hilar lymphadenectomy was performed in 16 (13.1%) cases. CL was performed on 110 (90.2%) patients, segmentectomy on 10 (8.2%), and completion pneumonectomy on 2 (1.6%). Upon reoperation, moderate pleural adhesions were observed in 38 (31.1%) patients, with 2 (1.6%) exhibiting strong adhesions. Moderate hilar adhesions were found in 18 (14.8%) patients and strong adhesions in 11 (9.0%). The median operative time was 203.93 ± 74.4 min. In four (3.3%) patients, PA taping was performed. One patient experienced intraoperative bleeding that did not require conversion to thoracotomy. Conversion to thoracotomy was necessary in three (2.5%) patients. The median postoperative drainage stay and postoperative hospital stay were 5.67 ± 4.44 and 5.52 ± 2.66 days, respectively. Postoperative complications occurred in 34 (27.9%) patients. Thirty-day mortality was null. Histology was the only factor found to negatively influence intraoperative outcomes (p = 0.000). Factors identified as negatively impacting postoperative outcomes at univariate analyses were male sex (p = 0.003), age > 60 years (p = 0.003), COPD (p = 0.014), previous thoracotomy (p = 0.000), previous S2 segmentectomy (p = 0.001), previous S8 segmentectomy (p = 0.008), and interval between operations > 5 weeks (p= 0.005). In multivariate analysis, only COPD confirmed its role as an independent risk factor for postoperative complications (HR: 5.12, 95% CI (1.07–24.50), p = 0.04). Conclusions: U-VATS CL seems feasible and safe after wedge resection and anatomical segmentectomy. [ABSTRACT FROM AUTHOR]

Simple Summary: Percutaneous cryoablation (PCA) is a minimally invasive procedure that should be considered in comorbid patients with stage T1 renal tumours who are suboptimal candidates for partial nephrectomy (PN). However, there is a scarcity of scientific data regarding the efficacy of PCA. The aim of this meta-analysis was to compare PCA and PN in terms of complications, renal function and survival outcomes. According to this analysis, PCA is associated with fewer complications than PN. Moreover, in tumours up to 4 cm, it provides the same time without local recurrence. Therefore, PCA should be proposed to patients with cT1 renal tumours who are not fit for PN but want to undergo a radical treatment. Percutaneous cryoablation (PCA) can be an alternative to partial nephrectomy (PN) in selected patients with stage T1 renal tumours. Existing meta-analyses regarding ablative techniques compared both laparoscopic and PCA with PN. That is why we decided to perform a meta-analysis that focused solely on PCA. The aim of this study was to compare the complications and functional and oncological outcomes between PCA and PN. A systematic literature search was performed in January 2024. Data for dichotomous and continuous variables were expressed as pooled odds ratios (ORs) and mean differences (MDs), both with 95% confidence intervals (CIs). Effect measures for the local recurrence-free survival (LRFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were expressed as pooled hazard ratios with 95% CIs. Among 6487 patients included in the 14 selected papers, 1554 (23.9%) and 4924 (76.1%) underwent PCA and PN, respectively. Compared with the PN group, patients undergoing PCA had significantly lower overall and major postoperative complication rates. There was no difference in renal function between PCA and PN groups. When analysing collective data for cT1 renal carcinoma, PCA was associated with worse LRFS compared with PN. However, subgroup analysis revealed that in the case of PCA, LRFS was not decreased in patients with cT1a tumours. Moreover, patients undergoing robotic-assisted PN had improved LRFS compared with those undergoing PCA. No significant differences were observed between PCA and PN in terms of MFS and CSS. Finally, PCA was associated with worse OS than PN in both collective and subgroup analyses. In conclusion, PCA is associated with favourable postoperative complication rates relative to PN. Regarding LRFS, PCA is not worse than PN in cT1a tumours but has a substantially relevant disadvantage in cT1b tumours. Also, RAPN might be the only surgical modality that provides better LRFS than PCA. In cT1 tumours, PCA shows MFS and CSS comparable to PN. Lastly, PCA is associated with a shorter OS than PN. [ABSTRACT FROM AUTHOR]

Simple Summary: The Sarcoma Assessment Measure (SAM) is a special questionnaire for patients with sarcomas, a type of cancer. It was created with input from both patients and healthcare professionals and is meant to be used by professionals to better understand how sarcoma affects a patient's life. We tested the SAM on 762 patients who had different types of sarcomas and ranged in age from 13 to 82. We found that the SAM could be a useful tool for both researchers and healthcare professionals to assess how sarcoma symptoms impact a patient's life. However, more testing with a larger and more diverse group of patients is needed to be sure it is a good outcome measure in drug trials. The Sarcoma Assessment Measure (SAM) was developed as a sarcoma-specific patient-reported outcome measure to be used in clinical practice. We have reported in detail how SAM has been developed in collaboration with patients and healthcare professionals. The aim of this paper is to report the preliminary validation of SAM. The 22-item SAM was administered alongside a validated quality of life questionnaire and measure of activities of daily living. Linear modelling was used to build a measure, which had predictive validity in comparison to more established outcome measures. Of the 762 patients who participated in the study, 44.1% identified as male, and participant age ranged from 13 to 82 years. Clinically, participants presented with a range of soft tissue (82.2%) and bone (21.8%) sarcomas. Our preliminary analysis indicates that SAM accounts for 35% of the global quality of life scale and 18% of the Toronto Extremity Salvage Scale (TESS); so psychometrically, it overlaps with quality of life and activities of daily living, but also measures distinct concerns. This demonstrates that this measure picks up issues that are important to patients with sarcoma that are not reflected in other measures. We have established the preliminary validity of SAM and believe it has utility as a patient-reported outcome measure both as a research tool and for assessing the impact of symptoms and dysfunction related to sarcoma as part of clinical care. Further validation using a larger and more clinically diverse sample is now needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck tumors (HNTs) are associated with a high mortality due to their commonly insidious and asymptomatic development. Regarding risk stratification and long-term patient outcome prediction, routine clinical evaluation by radiologists has several limitations. Numerous researchers have assessed the usefulness of radiomics and artificial intelligence in the context of head and neck tumor imaging given the exponential development of these technologies in medical imaging. These were geared at the creation of reliable and reproducible models based on quantitative data. Even if there are still a few obstacles to their widespread usage in clinical practice, it is clear that they have the potential to be revolutionary. In this paper, we provide a thorough overview of radiomics and artificial intelligence applications in head and neck tumor imaging. Recent advances in machine learning and artificial intelligence technology have ensured automated evaluation of medical images. As a result, quantifiable diagnostic and prognostic biomarkers have been created. We discuss radiomics applications for the head and neck region in this paper. Molecular characterization, categorization, prognosis and therapy recommendation are given special consideration. In a narrative manner, we outline the fundamental technological principles, the overall idea and usual workflow of radiomic analysis and what seem to be the present and potential challenges in normal clinical practice. Clinical oncology intends for all of this to ensure informed decision support for personalized and useful cancer treatment. Head and neck cancers present a unique set of diagnostic and therapeutic challenges. These challenges are brought on by the complicated anatomy and heterogeneity of the area under investigation. Radiomics has the potential to address these barriers. Future research must be interdisciplinary and focus on the study of certain oncologic functions and outcomes, with external validation and multi-institutional cooperation in order to achieve this. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a feasible method of intraperitoneal drug administration in patients affected by peritoneal cancer of primary or secondary origin. We performed a systematic review and meta-analysis with the aim of assessing the feasibility, safety, and efficacy of PIPAC. Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel intraperitoneal drug delivery method of low-dose chemotherapy as a pressurized aerosol in patients affected by peritoneal cancer of primary or secondary origin. We performed a systematic review and meta-analysis with the aim of assessing the feasibility, safety, and efficacy of PIPAC. Methods: A systematic literature search was performed using Medline and Web of Science databases from 1 January 2011, to inception, to 31 December 2021. Data were independently extracted by two authors. The Newcastle-Ottawa Scale was used to assess the quality and risk of bias of studies. Meta-analysis was performed for pathological response, radiological response, PCI variation along treatment, and for patients undergoing three or more PIPAC. Pooled analyses were performed using the Freeman–Tukey double arcsine transformation, and 95% CIs were calculated using Clopper–Pearson exact CIs in all instances. Results: A total of 414 papers on PIPAC were identified, and 53 studies considering 4719 PIPAC procedure in 1990 patients were included for analysis. The non-access rate or inability to perform PIPAC pooled rate was 4% of the procedures performed. The overall proportion of patients who completed 3 or more cycles of PIPAC was 39%. Severe toxicities considering CTCAE 3–4 were 4% (0% to 38.5%). In total, 50 studies evaluated deaths within the first 30 postoperative days. In the included 1936 patients were registered 26 deaths (1.3%). The pooled analysis of all the studies reporting a pathological response was 68% (95% CI 0.61–0.73), with an acceptable heterogeneity (I2 28.41%, p = 0.09). In total, 10 papers reported data regarding the radiological response, with high heterogeneity and a weighted means of 15% (0% to 77.8%). PCI variation along PIPAC cycles were reported in 14 studies. PCI diminished, increased, or remained stable in eight, one and five studies, respectively, with high heterogeneity at pooled analysis. Regarding survival, there was high heterogeneity. The 12-month estimated survival from first PIPAC for colorectal cancer, gastric cancer, gynecological cancer and hepatobiliary/pancreatic cancer were, respectively, 53%, 25%, 59% and 37%. Conclusions: PIPAC may be a useful treatment option for selected patients with PM, with acceptable grade 3 and 4 toxicity and promising survival benefit. Meta-analysis showed high heterogeneity of data among up-to-date available studies. In a subset analysis per primary tumor origin, pathological tumor regression was documented in 68% of the studies with acceptable heterogeneity. Pathological regression seems, therefore, a reliable outcome for PIPAC activity and a potential surrogate endpoint of treatment response. We recommend uniform selection criteria for patients entering a PIPAC program and highlight the urgent need to standardize items for PIPAC reports and datasets. [ABSTRACT FROM AUTHOR]

Simple Summary: The expression of the cysteine–glutamate cotransporter, system xc−, is increased in cancer cells across many cancer types. Imaging system xc− provides new insights into tumour behaviour. The radiotracer (4S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid (18F-FSPG) is specifically transported by system xc−, allowing for a non-invasive method of measuring this transporter's activity. This review summarises the data available on the use of 18F-FSPG in human cancer patients, exploring its advantages and disadvantages, and suggests possible future uses of 18F-FSPG in the assessment of early treatment response and treatment resistance. System xc− is upregulated in cancer cells and can be imaged using novel radiotracers, most commonly with (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid (18F-FSPG). The aim of this review was to summarise the use of 18F-FSPG in humans, explore the benefits and limitations of 18F-FSPG, and assess the potential for further use of 18F-FSPG in cancer patients. To date, ten papers have described the use of 18F-FSPG in human cancers. These studies involved small numbers of patients (range 1–26) and assessed the use of 18F-FSPG as a general oncological diagnostic agent across different cancer types. These clinical trials were contrasting in their findings, limiting the scope of 18F-FSPG PET/CT as a purely diagnostic agent, primarily due to heterogeneity of 18F-FSPG retention both between cancer types and patients. Despite these limitations, a potential further application for 18F-FSPG is in the assessment of early treatment response and prediction of treatment resistance. Animal models of cancer have shown that changes in 18F-FSPG retention following effective therapy precede glycolytic changes, as indicated by 18F-FDG, and changes in tumour volume, as measured by CT. If these results could be replicated in human clinical trials, imaging with 18F-FSPG PET/CT would offer an exciting route towards addressing the currently unmet clinical needs of treatment resistance prediction and early imaging assessment of therapy response. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor gene (EGFR) Exon 20 insertion mutations (Exon20ins) used to have poor outcomes after the failure of platinum-based therapies. Amivantamab, a drug that targets two proteins involved in NSCLC (EGFR/MET), was developed and studied in the CHRYSALIS clinical trial. This paper summarizes an analysis comparing outcomes for amivantamab from CHRYSALIS to the outcomes for a mix of treatments that were used in real-world clinical practice (real-world physician's choice [RWPC]). RWPC data were collected from hospitals across Europe in the CATERPILLAR real-world evidence (RWE) study. The outcomes of 114 patients from CHRYSALIS were compared to 55 lines of treatment (LOTs) from CATERPILLAR-RWE, accounting for differences in patient characteristics between the two populations. Overall, the results show that amivantamab was at least twice as good as RWPC for platinum pre-treated patients in terms of tumor response and survival rates. Patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor gene (EGFR) Exon 20 insertions (Exon20ins) at the second line and beyond (2L+) have an unmet need for new treatment. Amivantamab, a bispecific EGFR- and MET-targeted antibody, demonstrated efficacy in this setting in the phase 1b, open-label CHRYSALIS trial (NCT02609776). The primary objective was to compare the efficacy of amivantamab to the choices made by real-world physicians (RWPC) using an external control cohort from the real-world evidence (RWE) chart review study, CATERPILLAR-RWE. Adjustment was conducted to address differences in prognostic variables between cohorts using inverse probability weighting (IPW) and covariate adjustments based on multivariable regression. In total, 114 patients from CHRYSALIS were compared for 55 lines of therapy from CATERPILLAR-RWE. Baseline characteristics were comparable between the amivantamab and IPW-weighted RWPC cohorts. For amivantamab versus RWPC using IPW adjustment, the response rate ratio for the overall response was 2.14 (p = 0.0181), and the progression-free survival (PFS), time-to-next-treatment (TTNT) and overall survival (OS) hazard ratios (HRs) were 0.42 (p < 0.0001), 0.47 (p = 0.0063) and 0.48 (p = 0.0207), respectively. These analyses provide evidence of clinical and statistical benefits across multiple outcomes and adjustment methods, of amivantamab in platinum pre-treated patients with advanced NSCLC harboring EGFR Exon20ins. These results confirm earlier comparisons versus pooled national registry data. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatoblastoma is a rare childhood liver cancer with poor outcomes for high-risk patients. Better treatments and better ways of identifying patients who respond poorly to treatment are needed. This paper uses new methods for identifying chemicals or metabolites produced in the tumour. By comparing the profiles of these metabolites in tumour tissue versus normal liver tissue taken from the same patient, we demonstrated that some metabolites differ significantly in hepatoblastoma. This correlates with gene expression data, suggesting that we identified the metabolites correctly. We also stained tumour tissues for proteins (enzymes) that regulate transport of fatty acids into the mitochondria, which are the cell's powerhouses. Taken together, our results indicate that tumour cells change the energy sources they use and rewire the cellular systems accordingly. Further work is required to verify this, but these leads could improve our understanding of the disease and lead to the development of novel therapies. Hepatoblastoma (HB) is a rare childhood tumour with an evolving molecular landscape. We present the first comprehensive metabolomic analysis using untargeted and targeted liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/MS) of paired tumour and non-tumour surgical samples in HB patients (n = 8 pairs). This study demonstrates that the metabolomic landscape of HB is distinct from that of non-tumour (NT) liver tissue, with 35 differentially abundant metabolites mapping onto pathways such as fatty acid transport, glycolysis, the tricarboxylic acid (TCA) cycle, branched-chain amino acid degradation and glutathione synthesis. Targeted metabolomics demonstrated reduced short-chain acylcarnitines and a relative accumulation of branched-chain amino acids. Medium- and long-chain acylcarnitines in HB were similar to those in NT. The metabolomic changes reported are consistent with previously reported transcriptomic data from tumour and non-tumour samples (49 out of 54 targets) as well as metabolomic data obtained using other techniques. Gene set enrichment analysis (GSEA) from RNAseq data (n = 32 paired HB and NT samples) demonstrated a downregulation of the carnitine metabolome and immunohistochemistry showed a reduction in CPT1a (n = 15 pairs), which transports fatty acids into the mitochondria, suggesting a lack of utilisation of long-chain fatty acids in HB. Thus, our findings suggest a reduced metabolic flux in HB which is corroborated at the gene expression and protein levels. Further work could yield novel insights and new therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain MRI scans often require different imaging sequences based on tissue types, posing a common challenge. In our research, we propose a method that utilizes Generative Adversarial Networks (GAN) to translate T2-weighted-Fluid-attenuated-Inversion-Recovery (FLAIR) MRI volumes into T2-Weighted (T2W) volumes, and vice versa. To evaluate the effectiveness of our approach, we introduce a novel evaluation schema that incorporates radiomic features. We train two distinct GAN-based architectures, namely Cycle GAN and Dual Cycle-Consistent Adversarial network (DC2Anet), using 510 pair-slices from 102 patients. Our findings indicate that the generative methods can produce results similar to the original sequence without significant changes in radiometric features. This method has the potential to assist clinicians in making informed decisions based on generated images when alternative sequences are unavailable, or time constraints prevent re-scanning MRI patients. One of the most common challenges in brain MRI scans is to perform different MRI sequences depending on the type and properties of tissues. In this paper, we propose a generative method to translate T2-Weighted (T2W) Magnetic Resonance Imaging (MRI) volume from T2-weight-Fluid-attenuated-Inversion-Recovery (FLAIR) and vice versa using Generative Adversarial Networks (GAN). To evaluate the proposed method, we propose a novel evaluation schema for generative and synthetic approaches based on radiomic features. For the evaluation purpose, we consider 510 pair-slices from 102 patients to train two different GAN-based architectures Cycle GAN and Dual Cycle-Consistent Adversarial network (DC2Anet). The results indicate that generative methods can produce similar results to the original sequence without significant change in the radiometric feature. Therefore, such a method can assist clinics to make decisions based on the generated image when different sequences are not available or there is not enough time to re-perform the MRI scans. [ABSTRACT FROM AUTHOR]

Simple Summary: The research paper reported on a newly developed screening technique called Microtube Array Membrane Hollow Fiber Assay (MTAM-HFA) used for determining the most effective medication for breast cancer patients. The study found that the MTAM-HFA approach had a high level of accuracy in predicting the patient's response to the medication therapy, and there was a significant correlation between the screening outcome and the clinical outcome. The findings suggest that the MTAM-HFA technique has great potential for developing customized therapy for cancer care. With its ability to identify precise therapies for breast cancer patients, the MTAM-HFA screening method could transform cancer therapy, resulting in better outcomes for patients. The study provides valuable information for healthcare professionals and researchers working on breast cancer therapy research. Breast cancer is a severe public health problem, and early treatment with powerful anticancer drugs is critical for success. The researchers investigated the clinical results of a novel screening tool termed Microtube Array Membrane Hollow Fiber Assay (MTAM-HFA) in breast cancer patients in this clinical investigation. In all trial participants, the MTAM-HFA was utilized to identify active medicines for the treatment of breast cancer. The MTAM-HFA was shown to be extremely useful in predicting patient response to anticancer medication therapy in this study. Furthermore, the substantial association between the MTAM-HFA screening outcome and the clinical outcome of the respective patients emphasizes the promise of this unique screening technology in discovering effective anticancer medication combinations for the treatment of breast cancer. These findings indicate that the MTAM-HFA has clinical significance and might be a valuable tool in the development of tailored therapy for cancer care. This study provides helpful information for physicians and scientists working on breast cancer therapy research. The potential benefits of employing MTAM-HFA to find accurate therapies for breast cancer patients might lead to enhanced personalized medicine approaches to cancer care, resulting in better patient outcomes. Overall, the MTAM-HFA screening approach has the potential to revolutionize customized cancer therapy, providing hope to both patients and physicians. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton therapy is a potentially attractive option to treat oropharyngeal cancers due to better dose distribution. We aimed to synthesize the quality of life (QOL) and patient-reported outcomes (PROs) following treatment. We found that studies frequently demonstrated the advantages of proton therapy compared to photon therapy in terms of QOL and PROs; however, biases due to the non-randomized nature of the studies may require confirmation in phase III randomized controlled trials. Background: Complex anatomy surrounding the oropharynx makes proton therapy (PT), especially intensity-modulated PT (IMPT), a potentially attractive option due to its ability to reduce the volume of irradiated healthy tissues. Dosimetric improvement may not translate to clinically relevant benefits. As outcome data are emerging, we aimed to evaluate the evidence of the quality of life (QOL) and patient-reported outcomes (PROs) following PT for oropharyngeal carcinoma (OC). Materials and Methods: We searched PubMed and Scopus electronic databases (date: 15 February 2023) to identify original studies on QOL and PROs following PT for OC. We employed a fluid strategy in the search strategy by tracking citations of the initially selected studies. Reports were extracted for information on demographics, main results, and clinical and dose factor correlates. Quality assessment was performed using the NIH's Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The PRISMA guidelines were followed in the preparation of this report. Results: Seven reports were selected, including one from a recently published paper captured from citation tracking. Five compared PT and photon-based therapy, although none were randomized controlled trials. Most endpoints with significant differences favored PT, including xerostomia, cough, need for nutritional supplements, dysgeusia, food taste, appetite, and general symptoms. However, some endpoints favored photon-based therapy (sexual symptoms) or showed no significant difference (e.g., fatigue, pain, sleep, mouth sores). The PROs and QOL improve following PT but do not appear to return to baseline. Conclusion: Evidence suggests that PT causes less QOL and PRO deterioration than photon-based therapy. Biases due to the non-randomized study design remain obstacles to a firm conclusion. Whether or not PT is cost-effective should be the subject of further investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal metastases have a poor prognosis, and one potential treatment option is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). The specific role of HIPEC is still poorly defined. In this cross-sectional study, we systematically analyzed all HIPEC trials registered on ClinicalTrials.gov to identify current research areas and to provide a perspective on expected outcomes. Only 11% (n = 26) of HIPEC trials registered on ClinicalTrials.gov (n = 234) have been published. The registered trials are very heterogeneous regarding methodological approaches and study designs. Currently, research is being conducted on 20 different drugs. The most studied cancers in HIPEC trials are peritoneal metastatic colorectal tumors, gastric cancer, and ovarian cancer. Introduction: Over the past two decades, cytoreductive surgery and HIPEC has improved outcomes for selected patients with peritoneal metastasis from various origins. This is a cross-sectional study with descriptive analyses of HIPEC trials registered on ClinicalTrials.gov. This study aimed to characterize clinical trials on HIPEC registered on ClinicalTrials.gov with the primary objective of identifying a trial focus and to examine whether trial results were published. Methods: The search included trials registered from 1 January 2001 to 14 March 2022. We examined the associations of exposure variables and other trial features with two primary outcomes: therapeutic focus and results reporting. Results: In total, 234 clinical trials were identified; 26 (11%) were already published, and 15 (6%) trials have reported their results but have not been published as full papers. Among ongoing nonpublished trials, 81 (39%) were randomized, 30 (14%) were blinded, n = 39 (20%) were later phase trials (i.e., phases 3 and 4), n = 152 (73%) were from a single institution, and 91 (44%) had parallel groups. Most of the trials were recruiting at the time of this analysis (75, 36%), and 39 (20%) were completed but had yet to publish results. In total, 68% of the trials focused on treatment strategies, and 53% investigated the oncological outcome. The most studied neoplasms for HIPEC trials were peritoneally metastasized colorectal cancer (32%), gastric cancer (29%), and ovarian cancer (26%). Twenty different drugs were analyzed in these clinical trials. Conclusions: Many study results are awaited from ongoing HIPEC trials. Most HIPEC trials focused on gastric, colorectal, or ovarian cancer. Many clinical trials were identified involving multiple entities and chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Simple Summary: Papillary thyroid carcinoma is still the most common endocrine tumor, most of which can be diagnosed by pathological results. However, there is still a small number of cases that are difficult to judge malignancy. In this study, we performed an integrative analysis of DNA methylation and RNA array from our cohort for potential papillary thyroid cancer-specific indicators. SERINC2, one of the differentially methylated and expressed genes, was first identified as a potential tumor-driven indicator in papillary thyroid carcinoma. We confirmed the influence of SERINC2 on proliferation and apoptosis in vitro after intervention or overexpression. Furthermore, we found tryptophan metabolism as a potential pathway targeted by SERINC2 through the investigation of data from the Cancer Dependency Map. In conclusion, our results demonstrate the whole-genome DNA methylation and gene expression profiles of papillary thyroid carcinoma, identify a new tumor-driven indicator, and provide a novel insight into the etiology of papillary thyroid cancer. Most papillary thyroid carcinomas (PTCs) can be diagnosed preoperatively by routine evaluation, such as thyroid ultrasonography and fine-needle aspiration biopsy. Nevertheless, understanding how to differentiate indolent thyroid tumors from aggressive thyroid cancers remains a challenge, which may cause overtreatment. This study aimed to identify papillary thyroid cancer-specific indicators with whole-genome DNA methylation and gene expression profiles utilizing Infinium Methylation EPIC BeadChip (850k) and RNA arrays. In this paper, we report SERINC2 as a potential tumor-driven indicator in PTC. The up-regulated expression levels of SERINC2 were verified in PTC cell lines via qPCR. Then, cell counting kit 8 (CCK-8), wound healing, and flow cytometric assays were performed to confirm the influence of SERINC2 on proliferation and apoptosis in PTC cell lines after intervention or overexpression. Moreover, the investigation of data from the Cancer Dependency Map (DepMap) provided a potential pathway targeted by SERINC2. The activation of the tryptophan metabolic pathway may reduce the dependency of SERINC2 in thyroid cancers. In conclusion, our results demonstrate the whole-genome DNA methylation and gene expression profiles of papillary thyroid carcinoma, identify SERINC2 as a potential tumor-driven biomarker, and preliminarily verify its function in PTC. [ABSTRACT FROM AUTHOR]

Simple Summary: Uveal melanoma is a rare form of melanoma but is the most common tumor in the eye. Despite having effective treatments for the initial tumor, many patients experience the spread of their cancer to distant body sites. There is no uniform way of treating metastatic disease, but physicians often use therapies that harness the patient's immune system because these same treatments have been very effective in other types of melanoma. Not all patients respond to this therapy though, and some develop toxicity related to the treatment. The goal of this paper was to identify features or blood markers that may help determine response to treatment early. Specifically, we analyzed a molecule called lactate dehydrogenase (LDH) and the ratio of different white blood cells at the start of therapy and 2 months after treatment was started. We found that these non-invasive blood markers could be useful in determining which patients are responding to treatment. Background: There is no standardized treatment for metastatic uveal melanoma (MUM) but immune checkpoint inhibitors (ICI) are increasingly used. While ICI has transformed the survival of metastatic cutaneous melanoma, MUM patients do not equally benefit. Factors known to affect ICI response include the hematologic markers, lactate dehydrogenase (LDH) and neutrophil:lymphocyte ratio (NLR). We evaluated the prognostic value of LDH and NLR at the start of ICI and on treatment in MUM. Methods: MUM patients were treated between August 2006 and May 2022 with combination ipilimumab/nivolumab or ipilimumab/nivolumab/pembrolizumab single-agent therapy. Univariable (UVA) and multivariable (MVA) analyses were used to assess the prognostic value of predefined baseline factors on progression-free (PFS) and overall survival (OS). Results: In forty-six patients with MUM treated with ICI, elevated baseline and on-treatment LDH was prognostic for OS (start of ICI, HR (95% CI): 3.6 (1.9–7.0), p < 0.01; on-treatment, HR (95% CI): 3.7 (1.6–8.8), p < 0.01) and PFS (start of ICI, (HR (95% CI): 2.8 (1.5–5.4), p < 0.0001); on-treatment LDH (HR (95% CI): 2.2 (1.1–4.3), p < 0.01). On-treatment NLR was prognostic for PFS (HR (95% CI): 1.9 (1.0–3.9), p < 0.01). On-treatment LDH remained an important contributor to survival on MVA (OS: HR (95% CI): 1.001 (1.00–1.002), p < 0.05); PFS: HR (95% CI): 1.001 (1.00–1.002), p < 0.01). Conclusions: This study demonstrates that LDH and NLR could be useful in the prognostication of MUM patients treated with ICI. Additional studies are needed to confirm the importance of these and other prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy has revolutionized the therapeutic options for patients living with non-small-cell lung cancer (NSCLC). Despite the unprecedented results achieved through immunotherapy, a low body mass index, which is referred to as cachexia, and the bacterial composition of the gut microbiota are known factors associated with resistance. In this paper, we enrolled 113 Japanese patients with NSCLC and demonstrated that cachexia was associated with poor outcomes. Moreover, microbiota sequencing revealed that patients without cachexia had abundant bacteria that correlated with a beneficial outcome. Altogether, our results demonstrated an association between the gut microbiota and cachexia. This study provides a rationale to launch clinical trials on the outcome of shifting the microbiota composition of patients with cachexia that are receiving immunotherapy. Cancer cachexia exerts a negative clinical influence on patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI). The prognostic impact of body weight change during ICI treatment remains unknown. The gut microbiota (GM) is a key contributor to the response to ICI therapy in cancer patients. However, the association between cancer cachexia and GM and their association with the response to ICIs remains unexplored. This study examined the association of cancer cachexia with GM composition and assessed the impact of GM on clinical outcomes in patients with NSCLC treated with ICIs. In this observational, prospective study, which included 113 Japanese patients with advanced NSCLC treated with ICIs, the prevalence of cachexia was 50.4% (57/113). The median progression-free survival (PFS) and overall survival (OS) were significantly shorter in the cachexia group than in the non-cachexia group (4.3 vs. 11.6 months (p = 0.003) and 12.0 months vs. not reached (p = 0.02), respectively). A multivariable analysis revealed that baseline cachexia was independently associated with a shorter PFS. Moreover, a gain in body weight from the baseline (reversible cachexia) was associated with a significantly longer PFS and OS compared to irreversible cachexia. Microbiome profiling with 16S rRNA analysis revealed that the cachexia group presented an overrepresentation of the commensal bacteria, Escherichia-Shigella and Hungatella, while the non-cachexia group had a preponderance of Anaerostipes, Blautia, and Eubacterium ventriosum. Anaerostipes and E. ventriosum were associated with longer PFS and OS. Moreover, a cachexia status correlated with the systemic inflammatory marker-derived-neutrophil-to-lymphocytes ratio (dNLR) and Lung Immune Prognostic Index (LIPI) indexes. Our study demonstrates that cachexia and longitudinal bodyweight change have a prognostic impact on patients with advanced NSCLC treated with ICI therapy. Moreover, our study demonstrates that bacteria associated with ICI resistance are also linked to cachexia. Targeted microbiota interventions may represent a new type of treatment to overcome cachexia in patients with NSCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic prostate cancer (mPCa) is one of the most common solid tumors in men and both the disease and the treatments affect patients' quality of life (QoL). Patient-reported Outcome Measurements (PROMs) are important to assess the patient's subjective experience with disease and treatment. Our aim is to appraise, compare, and summarize the psychometric properties of Patient-reported Outcome Measures (PROMs). Our findings can improve patients' care and their quality of life during treatment and the disease path. Introduction: Patient-reported outcome measures (PROMs) represent important endpoints in metastatic prostate cancer (mPCa). However, the clinically valid and accurate measurement of health-related quality of life depends on the psychometric properties of the PROMs considered. Objective: To appraise, compare, and summarize the properties of PROMs in mPCa. Evidence acquisition: We performed a review of PROMs used in RCTs, including patients with mPCa, using Medline in September 2021, according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. This systematic review is part of PIONEER (an IMI2 European network of excellence for big data in PCa). Results: The most frequently used PROMs in RCTs of patients with mPCa were the Functional Assessment for Cancer Therapy—Prostate (FACT-P) (n = 18), the Brief Pain Inventory—Short Form (BPI-SF) (n = 8), and the European Organization for Research and Treatment of Cancer quality of life core 30 (EORTC QLQ-C30) (n = 6). A total of 283 abstracts were screened and 12 full-text studies were evaluated. A total of two, one, and two studies reported the psychometric proprieties of FACT-P, Brief Pain Inventory (BPI), and BPI-SF, respectively. FACT-P and BPI showed a high content validity, while BPI-SF showed a moderate content validity. FACT-P and BPI showed a high internal consistency (summarized by Cronbach's α 0.70–0.95). Conclusions: The use of BPI and FACT-P in mPCa patients is supported by their high content validity and internal consistency. Since BPI is focused on pain assessment, we recommend FACT-P, which provides a broader assessment of QoL and wellbeing, for the clinical evaluation of mPCa patients. However, these considerations have been elaborated on in a very limited number of studies. Patient summary: In this paper, we review the psychometric properties of PROMs used with patients with mPCa to find the questionnaires that best assess patients' QoL, in order to help professionals in their intervention and improve patients' QoL. We recommend the use of BPI and FACT-P for their high content validity and internal consistency despite the limited number of studies considered. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioma is the most common primary malignant tumor of the adult central nervous system. Despite aggressive multimodal treatment, its prognosis remains poor. During follow-up, it remains challenging to distinguish treatment-related changes from tumor progression in treated patients with gliomas due to both share clinical symptoms and morphological imaging characteristics (with new and/or increasing enhancing mass lesions). The early effective identification of tumor progression and treatment-related changes is of great significance for the prognosis and treatment of gliomas. We believe that advanced neuroimaging techniques can provide additional information for distinguishing both at an early stage. In this article, we focus on the research of magnetic resonance imaging technology and artificial intelligence in tumor progression and treatment-related changes. Finally, it provides new ideas and insights for clinical diagnosis. As the most common neuro-epithelial tumors of the central nervous system in adults, gliomas are highly malignant and easy to recurrence, with a dismal prognosis. Imaging studies are indispensable for tracking tumor progression (TP) or treatment-related changes (TRCs). During follow-up, distinguishing TRCs from TP in treated patients with gliomas remains challenging as both share similar clinical symptoms and morphological imaging characteristics (with new and/or increasing enhancing mass lesions) and fulfill criteria for progression. Thus, the early identification of TP and TRCs is of great significance for determining the prognosis and treatment. Histopathological biopsy is currently the gold standard for TP and TRC diagnosis. However, the invasive nature of this technique limits its clinical application. Advanced imaging methods (e.g., diffusion magnetic resonance imaging (MRI), perfusion MRI, magnetic resonance spectroscopy (MRS), positron emission tomography (PET), amide proton transfer (APT) and artificial intelligence (AI)) provide a non-invasive and feasible technical means for identifying of TP and TRCs at an early stage, which have recently become research hotspots. This paper reviews the current research on using the abovementioned advanced imaging methods to identify TP and TRCs of gliomas. First, the review focuses on the pathological changes of the two entities to establish a theoretical basis for imaging identification. Then, it elaborates on the application of different imaging techniques and AI in identifying the two entities. Finally, the current challenges and future prospects of these techniques and methods are discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, mostly driven by activating mutations in KIT or PDGFRα oncogenes. The introduction of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of GIST resulting in a substantial gain in median overall survival. Nowadays, imatinib, sunitinib, regorafenib, and ripretinib are registered as first, second, third, and fourth-line therapies, and avapritinib is registered specifically for GISTs harboring a PDGFRα exon 18/D842V mutation. As a result, health-related quality of life (HRQoL) has become more relevant for this surviving population, which is increasing in number. In daily clinical practice, the side effects of TKIs and their impact on the daily lives of patients are the main reason for treatment adjustments. Currently, an overview of HRQoL issues and side effects of different TKIs registered for the treatment of GIST is lacking. Background: The introduction of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of gastrointestinal stromal tumors (GISTs), resulting in a substantial gain in median overall survival. Subsequently, health-related quality of life (HRQoL) has become more relevant. Here, we systematically review the available literature on HRQoL issues and side effects of different TKIs registered for the treatment of GIST. Methods: A search through five databases was performed. Full reports in English describing HRQoL outcomes and/or side effects in GIST patients on TKI therapy were included. Results: A total of 104 papers were included; 13 studies addressed HRQoL, and 96 studies investigated adverse events. HRQoL in patients treated with imatinib, regorafenib, and ripretinib remained stable, whereas most sunitinib-treated patients reported a decrease in HRQoL. Severe fatigue and fear of recurrence or progression were specifically assessed as HRQoL issues and had a negative impact on overall HRQoL as well as psychological and physical well-being. The majority of studies focused on physician-reported side effects. Nearly all GIST patients treated with a TKI experienced at least one adverse event, mostly mild to moderate. Conclusions: Despite the fact that almost all patients treated with a TKI experienced side effects, this did not seem to affect overall HRQoL during TKI therapy. In daily practice, it are the side effects that hamper a patient's HRQoL resulting in treatment adjustments, suggesting that the reported side effects were underestimated by physicians, or the measures used to assess HRQoL do not capture all relevant issues that determine a GIST patient's HRQoL. [ABSTRACT FROM AUTHOR]

Simple Summary: When it comes to advanced vulval cancer management, there is a critical quandary to consider. This is owing to the severe negative impact of demolitive surgery on women who are afflicted by both functional and psychological consequences of the procedure. Primary closure of vulvar and/or perineal defects can be accomplished without difficulty in many situations, but this is accompanied by tension of the skin closure and distortion of the anatomy. In these circumstances, reconstructive surgery will be required to restore the anatomical and functional characteristics of the vulva. In this paper, we share our substantial expertise of primary closure versus reconstruction after demolitive surgery of advanced vulvar cancer, and we discuss our findings in light of the literature. (1) Background: plastic reconstruction in vulvar surgery can lead to a better treatment outcome than primary closure. This study aims to compare the preoperative parameters (co-morbidities and tumor size) and postoperative results (tumor free margins and wound healing) between the primary closure and reconstructive surgery after vulvar cancer surgery; (2) Methods: this is a retrospective analysis of prospectively collected data from 2009 to 2021 at a tertiary cancer institution; (3) Results: 177 patients were included in the final analysis (51 patients had primary closure PC and 126 had reconstructive surgery RS). About half (49%) of the PC patients had no co-morbidities (p = 0.043). The RS group had a 45 mm median maximal tumor diameter compared to the PC group's 23 mm (p = 0.013). More than 90% of RS and 80% of PC had tumor-free margins (p = 0.1). Both groups had anterior vulvar excision as the most common surgery (52.4% RS vs. 23.5% PC; p = 0.001). Both groups had identical rates of wound healing disorders. In a median follow-up of 39 months; recurrent disease was found in 23.5% of PC vs. 10.3% in RS (p = 0.012). In terms of overall survival there was no significant difference between the both groups; (4) Conclusions: reconstructive vulvar surgery enables enhanced complete resection rates of larger vulvar tumors with better anatomical restoration and a comparable wound recovery in comparison to primary closure. This results in a lower recurrence rate despite the increased tumor volume. [ABSTRACT FROM AUTHOR]

Simple Summary: In the era of direct-acting antiviral (DAA) agents, chronic hepatitis C virus (HCV) infection has become a curable disease. Eradication of the virus remains a major goal for the World Health Organization (WHO) by 2030. Main obstacles seem to be the lack of national screenings and shortage of knowledge among patients and healthcare professionals. There also remain, scarcely described in the literature, specific groups of patients who, due to their comorbidities such as malignant tumors, may not be considered as candidates eligible for DAA treatment. In our study, we aimed to characterize and present treatment efficacy in individuals with chronic hepatitis C and an active malignancy treated in Poland in years 2015–2020 with DAAs and compare their outcomes with a treated population with no active malignancy. The obtained results indicate high effectiveness and a low number of premature treatment discontinuations for the majority of patients with active malignancies, with some concerns around HCCs. We believe that data provided by this study will lead to more efficient elaboration of the standard of care in this population. Background: Over the past years, the introduction of direct-acting antivirals (DAAs) revolutionized chronic hepatitis C treatment. We aimed to characterize and assess treatment efficacy in three specific groups of patients treated with DAAs: those with active solid malignant tumors (SMTs), hematological diseases (HDs) and hepatocellular carcinomas (HCCs). Methods: A total of 203 patients with active oncological disease (SMT n = 61, HD = 67, HCC n = 74) during DAA treatment in 2015–2020 selected from the EpiTer-2 database were analyzed retrospectively and compared to 12,983 patients without any active malignancy. Results: Extrahepatic symptoms were more frequent in HD patients (17.2% vs. SMT = 10.3%, HCC = 8.2%, without = 7.8%, p = 0.004). HCC patients characterized with the highest ALT activity (81 IU/L vs. SMT = 59.5 IU/L, HD = 52 IU/L, without = 58 IU/L, p = 0.001) more often had F4 fibrosis as well (86.11% vs. SMT = 23.3%, HD = 28.8%, controls = 24.4%, p = 0.001). A significant majority of subjects in HCC, HD and SMT populations completed the full treatment plan (HCC = 91%; n = 67, HD = 97%; n = 65, SMT = 100%; n = 62). Concerning the treatment efficacy, the overall sustained virologic response, excluding non-virologic failures, was reported in 93.6% HD, 90.16% SMT and 80.6% in HCC patients. Conclusions: As presented in our study, DAA therapy has proven to be highly effective and safe in patients with active SMTs and HDs. However, therapy discontinuations resulting from liver disease progression remain to be the major concern in HCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Squamous cell carcinoma of the anus or anal cancer is increasing in prevalence, and the standard treatment of mitomycin and 5-fluorouracil is too toxic for many patients. Unfortunately, there is currently no standard of care for what to do for this disease when someone is not a candidate for this aggressive treatment. Here, we demonstrate the promising preliminary toxicity profile and efficacy of the combination of weekly carboplatin and paclitaxel chemotherapy for patients with localized anal cancer. This regimen was able to complete 80% of the intended treatments with anticipated toxicities, and 89% achieved a complete clinical response. This combination is a promising regimen and is already being investigated further in a clinical trial. Background: Although squamous cell carcinoma of the anus (SCCA) is a relatively uncommon malignancy in the United States, it continues to increase in incidence. Treatment for locoregional disease includes mitomycin and 5-fluorouracil with radiation. This combination is associated with significant toxicity, limiting its use in patients who are older or have certain comorbidities. Carboplatin and paclitaxel (C/P) is an accepted treatment regimen for metastatic SCCA. We aim to evaluate the efficacy and toxicity of weekly C/P given with radiation for patients unable to receive standard chemoradiation for SCCA. Methods: From our cancer registry, adult patients who received weekly intravenous C/P concurrent with standard-dose radiation for localized SCCA were included in this study. Clinical response was determined based on the evidence of disease on imaging and/or anoscopy. Toxicities were graded according to the CTCAE v5. Results: Ten patients were included; eight were female, and the median age was 75.5 years (54–87). Six had T2 disease, and four had T3 tumors. Four had node-positive disease. The majority (70%) of patients were dosed at standard C (AUC 2) and P (50 mg/m2), with a limited subset requiring dose reduction for baseline performance status. Patients completed a mean of 78.3% (40–100%) of the intended treatments. A total of 89% of the patients achieved a complete clinical response. With a median follow-up of 25.8 months (3.4–50.4 months), 67% of the patients are alive and without recurrence. Two patients have had local recurrence, and one patient had metastatic progression. The most common toxicities of any grade included leukopenia (100%), anemia (100%), radiation dermatitis (100%), diarrhea (100%), and fatigue (100%). Grade 3 or higher toxicities included neutropenic fever (20%), neutropenia (30%), and anemia (30%). Conclusions: This study demonstrates promising tolerability and efficacy for weekly C/P chemoradiation for patients with anal cancer unable to receive mitomycin and 5-fluorouracil. This regimen merits further investigation in prospective clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: This study evaluated the ability of Large Language Models (LLMs) to classify subjective toxicities from chemotherapy by comparing them with expert oncologists. Using fictitious cases, it was demonstrated that LLMs can achieve accuracy similar to that of oncologists in general toxicity categories, although they need improvement in specific categories. LLMs show great potential for enhancing patient monitoring and reducing the workload of doctors. Future research should focus on training LLMs specifically for medical tasks and validating these findings with real patients, always ensuring accuracy and ethical data management. Introduction: Large Language Models (LLMs), such as the GPT model family from OpenAI, have demonstrated transformative potential across various fields, especially in medicine. These models can understand and generate contextual text, adapting to new tasks without specific training. This versatility can revolutionize clinical practices by enhancing documentation, patient interaction, and decision-making processes. In oncology, LLMs offer the potential to significantly improve patient care through the continuous monitoring of chemotherapy-induced toxicities, which is a task that is often unmanageable for human resources alone. However, existing research has not sufficiently explored the accuracy of LLMs in identifying and assessing subjective toxicities based on patient descriptions. This study aims to fill this gap by evaluating the ability of LLMs to accurately classify these toxicities, facilitating personalized and continuous patient care. Methods: This comparative pilot study assessed the ability of an LLM to classify subjective toxicities from chemotherapy. Thirteen oncologists evaluated 30 fictitious cases created using expert knowledge and OpenAI's GPT-4. These evaluations, based on the CTCAE v.5 criteria, were compared to those of a contextualized LLM model. Metrics such as mode and mean of responses were used to gauge consensus. The accuracy of the LLM was analyzed in both general and specific toxicity categories, considering types of errors and false alarms. The study's results are intended to justify further research involving real patients. Results: The study revealed significant variability in oncologists' evaluations due to the lack of interaction with fictitious patients. The LLM model achieved an accuracy of 85.7% in general categories and 64.6% in specific categories using mean evaluations with mild errors at 96.4% and severe errors at 3.6%. False alarms occurred in 3% of cases. When comparing the LLM's performance to that of expert oncologists, individual accuracy ranged from 66.7% to 89.2% for general categories and 57.0% to 76.0% for specific categories. The 95% confidence intervals for the median accuracy of oncologists were 81.9% to 86.9% for general categories and 67.6% to 75.6% for specific categories. These benchmarks highlight the LLM's potential to achieve expert-level performance in classifying chemotherapy-induced toxicities. Discussion: The findings demonstrate that LLMs can classify subjective toxicities from chemotherapy with accuracy comparable to expert oncologists. The LLM achieved 85.7% accuracy in general categories and 64.6% in specific categories. While the model's general category performance falls within expert ranges, specific category accuracy requires improvement. The study's limitations include the use of fictitious cases, lack of patient interaction, and reliance on audio transcriptions. Nevertheless, LLMs show significant potential for enhancing patient monitoring and reducing oncologists' workload. Future research should focus on the specific training of LLMs for medical tasks, conducting studies with real patients, implementing interactive evaluations, expanding sample sizes, and ensuring robustness and generalization in diverse clinical settings. Conclusions: This study concludes that LLMs can classify subjective toxicities from chemotherapy with accuracy comparable to expert oncologists. The LLM's performance in general toxicity categories is within the expert range, but there is room for improvement in specific categories. LLMs have the potential to enhance patient monitoring, enable early interventions, and reduce severe complications, improving care quality and efficiency. Future research should involve specific training of LLMs, validation with real patients, and the incorporation of interactive capabilities for real-time patient interactions. Ethical considerations, including data accuracy, transparency, and privacy, are crucial for the safe integration of LLMs into clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: This research investigates the effectiveness and safety of totally implantable vascular access devices (TIVADs) used for delivering treatments such as chemotherapy. Over a five-year period, 70 patients received TIVADs through a standardized surgical method under local anesthesia. The study found very low complication rates, with only two notable incidents: one device needed adjustment due to a flipped catheter, and one infection occurred after over three years of use. The procedural success rate was 100%, with devices typically lasting around 22 months, and some even up to five years. These findings suggest that TIVADs are a reliable and safe option for long-term venous access, significantly benefiting routine clinical practices. Background: Daily clinical practice requires repeated and prolonged venous access for delivering chemotherapy, antibiotics, antivirals, parenteral nutrition, or blood transfusions. This study aimed to investigate the performance and the safety of totally implantable vascular access devices (TIVADs) over a 5-year follow-up period through a standardized well-trained surgical technique and patient management under local anesthesia. Methods: In a retrospective, observational, and monocentric study, 70 patients receiving POLYSITE® TIVADs for chemotherapy were included. The safety endpoints focused on the rate of perioperative, short-term, and long-term complications. The performance endpoints included vein identification for device insertion and procedural success rate. Results: The study demonstrated no perioperative or short-term complications related to the TIVADs. One (1.4%) complication related to device manipulation was identified as catheter flipping, which led to catheter adjustment 56 days post-placement. Moreover, one (1.4%) infection due to usage conditions was observed, leading to TIVAD removal 3 years and 4 months post-surgery. Catheter placement occurred in cephalic veins (71.4%), subclavian veins (20%), and internal jugular veins (8.6%). The procedural success rate was 100%. Overall, the implantable ports typically remained in place for an average of 22.4 months. Conclusions: This study confirmed the TIVADs' performance and safety, underscored by low complication rates compared to published data, thereby emphasizing its potential and compelling significance for enhancing routine clinical practice using a standardized well-trained surgical technique and patient management. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to evaluate the derived neutrophil to lymphocyte ratio (dNLR) in predicting the prognosis of patients with locally advanced oral squamous cell carcinoma, as well as the survival benefits from induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (5-FU). The dNLR is an independent negative predictive factor for the disease. Patients with cTNM stage III disease and a low dNLR may benefit from induction chemotherapy. Background: This study aimed to evaluate the derived neutrophil to lymphocyte ratio (dNLR) in predicting the prognosis of patients with locally advanced oral squamous cell carcinoma (LAOSCC) and to assess the survival benefits from docetaxel, cisplatin, and 5-fluorouracil (5-FU) (TPF) induction chemotherapy (IC). Methods: Patients from a phase III trial involving TPF IC in stage III/IVA OSCC patients (NCT01542931) were enrolled. Receiver operating characteristic curves were constructed, and the area under the curve was computed to determine dNLR cutoff points. Kaplan–Meier survival estimates and Cox proportional hazards models were used for longitudinal analysis. Results: A total of 224 patients were identified (median age: 55.4 years; range: 26 to 75 years; median follow-up: 90 months; range: 3.2 to 93 months). The cutoff point for the dNLR was 1.555. Multivariate analysis showed that the dNLR was an independent negative predictive factor for survival (overall survival (OS): hazard ratio (HR) = 1.154, 95% confidence interval (CI): 1.018–1.309, p = 0.025; disease-free survival (DFS): HR = 1.123, 95% CI: 1.000–1.260, p = 0.050; local recurrence-free survival (LRFS): HR = 1.134, 95% CI: 1.002–1.283, p = 0.047; distant metastasis-free survival (DMFS): HR = 1.146, 95% CI: 1.010–1.300, p = 0.035). A low dNLR combined with cTNM stage III disease predicted benefit from TPF IC for the patients [OS (χ2 = 4.674, p = 0.031), DFS (χ2 = 7.134, p = 0.008), LRFS (χ2 = 5.937, p = 0.015), and DMFS (χ2 = 4.832, p = 0.028)]. Conclusions: The dNLR is an independent negative predictive factor in LAOSCC patients. Patients with cTNM stage III disease and a low dNLR can benefit from TPF IC. [ABSTRACT FROM AUTHOR]

Simple Summary: Roughly 430,000 new cases of renal cell carcinoma (RCC) occurred worldwide in 2022, and about one-third of RCC cases are diagnosed at an advanced stage of disease (aRCC). When patients with aRCC fail first-line treatment, they commonly receive one of the recommended second-line treatments, i.e., axitinib, cabozantinib, lenvatinib plus everolimus, pazopanib, sunitinib, or tivozanib. Axitinib is a second-generation tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor tyrosine kinases 1, 2, and 3. It has been available since 2011 for the treatment of aRCC after the failure of prior therapy with sunitinib or cytokines. The aim of our research was to understand how axitinib compares with other treatment options considering data from clinical trials and observational studies that reflect real-world clinical practice. Therefore, we conducted a systematic literature review to summarise evidence on commonly used and recommended treatments in aRCC after the failure of prior therapy with sunitinib or cytokines. Background: We conducted a systematic literature review (SLR) to identify clinical evidence on treatments in advanced renal cell carcinoma (aRCC) after the failure of prior therapy with cytokines, tyrosine kinase inhibitors, or immune checkpoint inhibitors. Herein, we summarise the evidence for axitinib in aRCC after the failure of prior therapy with cytokines or sunitinib. Methods: This SLR was registered with PROSPERO (CRD42023492931) and followed the 2020 PRISMA statement and the Cochrane guidelines. Comprehensive searches were conducted in MEDLINE and Embase as well as for conference proceedings. Study eligibility was defined according to population, intervention, comparator, outcome, and study design. Results: Of 1252 titles/abstracts screened, 266 peer-reviewed publications were reviewed, of which 182 were included. In addition, 28 conference abstracts were eligible. Data on axitinib were reported in 55 publications, of which 16 provided efficacy and/or safety outcomes on axitinib after therapy with sunitinib or cytokines. In these patients, median progression-free and overall survival ranged between 5.5 and 8.7 months and 11.0 and 69.5 months, respectively. Conclusions: Axitinib is commonly used in clinical practice and has a well-characterised safety and efficacy profile in the treatment of patients with aRCC after the failure of prior therapy with sunitinib or cytokines. [ABSTRACT FROM AUTHOR]

Simple Summary: Indocyanine green (ICG) is a dye that helps surgeons see the blood supply to tissues. In this study, (MIRRORS ICG) researchers wanted to see if this dye could help find cancer in women with advanced ovarian cancer undergoing robotic surgery after chemotherapy. After injecting ICG, a special camera was used to look at the whole abdomen and pelvic area. In this study, 102 tissue samples were taken to see if ICG helped identify cancerous tissue. The results showed that ICG correctly identified cancer in 91.1% of cases but had a low specificity of 13.0%, meaning it often falsely indicated cancer. This technique did not significantly help in detecting cancer in patients with widespread disease, but it showed some potential in those who had responded well to chemotherapy and had few remaining cancer spots. Molecular imaging with targeted dyes could enhance precision surgery in the future. Indocyanine green (ICG) is a fluorescent dye used for sentinel lymph node assessment and the assessment of perfusion in skin flaps and bowel anastomoses. ICG binds serum proteins and behaves as a macromolecule in the circulation. Tumour tissue has increased vascular permeability and reduced drainage, causing macromolecules to accumulate within it. MIRRORS ICG is designed to determine whether indocyanine green (ICG) helped identify metastatic deposits in women undergoing robotic interval cytoreductive surgery for advanced-stage (3c+) ovarian cancer. Peritoneal surfaces of the abdominal and pelvic cavity were inspected under white light and near-infrared light (da Vinci Si and Xi Firefly Fluorescence imaging, Intuitive Surgical Inc.) following intravenous injection of 20 mg ICG in sterile water. Visibly abnormal areas were excised and sent to histopathology, noting IGC positivity. In total, 102 biopsies were assessed using ICG. Intravenous ICG assessment following neoadjuvant chemotherapy had a sensitivity of 91.1% (95% CI [82.6–96.4%]), a specificity of 13.0% (95% CI [2.8–33.6%]), a positive predictive value of 78.3% (95% CI [68.4–86.2%]), and a negative predictive value of 30.0% (95% CI [6.7–65.2%]) False-positive samples were seen in 9/20 patients. Psammoma bodies were noted in the histopathology reports of seven of nine of these patients with false-positive results, indicating that a tumour had been present (chemotherapy-treated disease). This study demonstrates the appearance of metastatic peritoneal deposits during robotic cytoreductive surgery following the intravenous administration of ICG in women who have undergone neoadjuvant chemotherapy for stage 3c+ advanced ovarian cancer. A perfusion assessment using indocyanine green (ICG) peritoneal angiography during robotic interval cytoreductive surgery for advanced ovarian cancer did not clinically improve metastatic disease identification in patients with high-volume disease. The use of ICG in patients with excellent response to chemotherapy where few tumour deposits remained shows some promise. The potential of molecular imaging to enhance precision surgery and improve disease identification using the robotic platform is a novel avenue for future research. [ABSTRACT FROM AUTHOR]

Simple Summary: High-dose-rate (HDR) brachytherapy (BT) is an effective treatment for bulky, middle, and advanced cervical cancer. Both 192Ir and 60Co are radiation sources recommended by the ICRU. Previously, due to the large geometric size of 60Co, 192Ir occupied most of the market share. After continuous technical improvements, the geometry of miniaturized 60Co sources has become comparable to that of 192Ir sources. Another important point is that people suspect that the use of 60Co sources will result in reduced efficacy, increased toxic reactions, and a series of issues. In this paper, we compared 60Co and 192Ir sources for HDR BT in terms of both dosimetry and clinical treatment. The results of reports published on the use of HDR BT for cervical cancer over the past few years as well as our own research show that this treatment is safe and 60Co can be promoted as a good alternative to 192Ir. High-dose-rate (HDR) brachytherapy (BT) is an essential treatment for cervical cancer, one of the most prevalent gynecological malignant tumors. In HDR BT, high radiation doses can be delivered to the tumor target with the minimum radiation doses to organs at risk. Despite the wide use of the small HDR 192Ir source, as the technique has improved, the HDR 60Co source, which has the same miniaturized geometry, has also been produced and put into clinical practice. Compared with 192Ir (74 days), 60Co has a longer half-life (5.3 years), which gives it a great economic advantage for developing nations. The aim of the study was to compare 60Co and 192Ir sources for HDR BT in terms of both dosimetry and clinical treatment. The results of reports published on the use of HDR BT for cervical cancer over the past few years as well as our own research show that this treatment is safe and it is feasible to use 60Co as an alternative source. [ABSTRACT FROM AUTHOR]

Simple Summary: Eotaxins are small proteins included in the group of chemokines. They act mainly on blood cells called eosinophils which are involved in the pathogenesis of inflammatory processes. This connection leads to involvement of eotaxins in the pathogenesis of all inflammatory related diseases, such as allergic diseases and cancer. This paper summarizes the current knowledge about eotaxins, showing their usefulness as markers that can be used not only in the detection of these diseases, but also to determine the effectiveness of treatment. Eotaxins are proteins which belong to the group of cytokines. These small molecules are secreted by cells that are mainly involved in immune-mediated reactions in the course of allergic diseases. Eotaxins were discovered in 1994 and their main role was considered to be the selective recruitment of eosinophils. As those blood cells are involved in the course of all inflammatory diseases, including cancer, we decided to perform an extensive search of the literature pertaining to our investigation via the MEDLINE/PubMed database. On the basis of available literature, we can assume that eotaxins can be used as markers for the detection and determination of origin or type of allergic disease. Many publications also confirm that eotaxins can be used in the determination of allergic disease treatment. Moreover, there are also studies indicating a connection between eotaxins and cancer. Some researchers revealed that CCL11 (C-C motif chemokine ligand 11, eotaxin-1) concentrations differed between the control and tested groups indicating their possible usefulness in cancer detection. Furthermore, some papers showed usefulness of eotaxins in determining the treatment efficacy as markers of decreasing inflammation. Therefore, in this paper we present the current knowledge on eotaxins in the course of allergic and cancerous diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Given the wide usage of Bevacizumab in current oncological practice, it is very important to compare the "real-world" results to those obtained in controlled clinical trials. This study aims to describe the clinical experience of using Bevacizumab in a large cohort of cancer patients in "non-controlled real-world" conditions regarding effectiveness, safety, and cost of therapy. For this purpose, we conducted an open, observational, retrospective study involving all patients treated for solid malignant tumors in the Bucharest Institute of Oncology with "Prof. Dr. Al. Trestioreanu" with Bevacizumab-based systemic therapy, between 2017 and 2021. Bevacizumab re-mains a high-cost therapy, but it can add to clinical benefits (like overall survival, progression-free survival, and response rate) when used in conjunction with standard chemotherapy. Similar results as those presented in various controlled trials are observable even on unselected cohorts of patients in the uncontrolled conditions of "real-world" oncological practice. Overall, it is estimated that more than 3,500,000 patients have received Bevacizumab as part of systemic oncologic treatment. Bevacizumab and its biosimilars are currently marketed in over 130 countries. Given the wide usage of Bevacizumab in current oncological practice, it is very important to compare the "real-world" results to those obtained in controlled clinical trials. This study aims to describe the clinical experience of using Bevacizumab in a large cohort of cancer patients in "non-controlled real-world" conditions with regard to effectiveness, safety, and cost of therapy. Methods: For this purpose, we conducted an open, observational, retrospective study involving all patients treated for solid malignant tumors in the Bucharest Institute of Oncology with "Prof. Dr. Al. Trestioreanu" with Bevacizumab-based systemic therapy, between 2017 and 2021. Results: The study consisted of 657 treatment episodes in 625 patients (F/B = 1.62/1, with a median age of 57.6 years) which were treated for malignant tumors (majority colorectal, non-small cell lung, ovarian, and breast cancer). First-line treatment was administered in 229 patients, and the rest received Bevacizumab as second or subsequent lines of treatment. The overall response rate to Bevacizumab-based therapies was around 60–65% across all indication except for subsequent treatment lines in colorectal and ovarian cancers, where lower values were recorded (27.1%, and 31.5% respectively). Median PFS for the entire cohort was 8.2 months (95% CI 6.8–9.6), and the median OS was 13.2 months (95% CI 11.5–14.9). Usual bevacizumab-related toxicities were observed, including bleeding, hypertension, wound-healing complications, gastrointestinal perforation, other types of fistulas, septic complications, and thromboembolic events. Although the clinical benefits are undeniable, the addition of Bevacizumab to standard chemotherapy increased the overall treatment cost by 213%. Conclusions: Bevacizumab remains a high-cost therapy, but it can add to clinical benefits (like overall survival, progression-free survival, and response rate) when used in conjunction with standard chemotherapy. Similar results as those presented in various controlled trials are observable even on unselected cohorts of patients in the uncontrolled conditions of "real-world" oncological practice. Off-label usage is encountered in clinical practice, and this aspect should be monitored given the potential adverse effects of the therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Gliomas are the most common type of malignant brain tumors in adults. They are frequently heterogeneous, containing regions of varying properties and aggressiveness. It can be challenging to define the tumor borders and identify the most aggressive parts of the tumor based on MRI alone. This study investigates whether PET imaging with amino acid tracer [18F]-FACBC can provide additional information on the composition of the tumor. The results suggest that uptake of the tracer could be used to identify aggressive tumor tissue with high accuracy, and with higher sensitivity than that of contrast-enhanced MRI. Background: Gliomas have a heterogeneous nature, and identifying the most aggressive parts of the tumor and defining tumor borders are important for histomolecular diagnosis, surgical resection, and radiation therapy planning. This study evaluated [18F]-FACBC PET for glioma tissue classification. Methods: Pre-surgical [18F]-FACBC PET/MR images were used during surgery and image-localized biopsy sampling in patients with high- and low-grade glioma. TBR was compared to histomolecular results to determine optimal threshold values, sensitivity, specificity, and AUC values for the classification of tumor tissue. Additionally, PET volumes were determined in patients with glioblastoma based on the optimal threshold. [18F]-FACBC PET volumes and diagnostic accuracy were compared to ce-T1 MRI. In total, 48 biopsies from 17 patients were analyzed. Results: [18F]-FACBC had low uptake in non-glioblastoma tumors, but overall higher sensitivity and specificity for the classification of tumor tissue (0.63 and 0.57) than ce-T1 MRI (0.24 and 0.43). Additionally, [18F]-FACBC TBR was an excellent classifier for IDH1-wildtype tumor tissue (AUC: 0.83, 95% CI: 0.71–0.96). In glioblastoma patients, PET tumor volumes were on average eight times larger than ce-T1 MRI volumes and included 87.5% of tumor-positive biopsies compared to 31.5% for ce-T1 MRI. Conclusion: The addition of [18F]-FACBC PET to conventional MRI could improve tumor classification and volume delineation. [ABSTRACT FROM AUTHOR]

Simple Summary: Chordoma is a rare cancer that often occurs at the base of the skull. Treating skull base chordoma is challenging because the tumor is difficult to completely remove with surgery and has low radiosensitivity. This study compared two types of radiation modality: particle beam therapy (PT) and photon radiotherapy (RT). We found that PT provides better progression-free survival compared to photon RT. However, PT also has a higher risk of causing brain necrosis. Our findings suggest that PT is more effective for controlling skull base chordoma, but careful planning is needed to minimize side effects. [Objective] The aim of this study was to compare the efficacy of particle beam therapy (PT) with photon radiotherapy (RT) for treatment of skull base chordoma. [Methods] A systematic review was conducted for skull base chordoma treated with PT or photon RT reported from 1990 to 2022. Data were extracted for overall survival (OS) and progression-free survival (PFS), late adverse events, age, gender, gross total resection (GTR) rates, tumor volume, total irradiation dose, and treatment modality. Random-effects meta-regression analysis with the treatment modality as an explanatory variable was performed for each outcome to compare the modalities. [Results] A meta-analysis of 30 selected articles found 3- and 5-year OS rates for PT vs. photon RT or combined photon RT/proton beam therapy (PBT) of 90.8% (95% CI: 87.4–93.3%) vs. 89.5% (95% CI: 83.0–93.6%), p = 0.6543; 80.0% (95% CI: 75.7–83.6%) vs. 89.5% (95% CI: 83.0–93.6%), p = 0.6787. The 5-year PFS rates for PT vs. photon RT or photon RT/PBT were 67.8% (95% CI: 56.5–76.7%) vs. 40.2% (95% CI: 31.6–48.7%), p = 0.0004. A random-effects model revealed that the treatment modality (PT vs. photon RT or photon RT/PBT) was not a significant factor for 3-year OS (p = 0.42) and 5-year OS (p = 0.11), but was a significant factor for 5-year PFS (p < 0.0001). The rates of brain necrosis were 8–50% after PT and 0–4% after photon RT or photon RT/PBT. [Conclusion] This study shows that PT results in higher PFS compared to photon RT for skull base chordoma, but that there is a tendency for a higher incidence of brain necrosis with PT. Publication and analysis of further studies is needed to validate these findings. [ABSTRACT FROM AUTHOR]

Simple Summary: High-dose post-transplant cyclophosphamide is effective in preventing graft-versus-host disease (GVHD) but is associated with adverse outcomes such as delayed engraftment, infections, and cardiac issues. This pilot study evaluated the efficacy and toxicity of reduced-dose PTCY (40 mg/kg/day) in patients undergoing HLA-matched allogeneic hematopoietic stem cell transplantation (alloHSCT). Neutrophil and platelet engraftment occurred at medians of 15 and 16 days, respectively. At day 100, the incidences of grade II–IV and III–IV acute GVHD were 18.2% and 4.5%, respectively, with no cases of grade IV acute GVHD or steroid-refractory disease. One-year incidence of moderate-severe chronic GVHD was 6.4%. Both incidences, acute GVHD and chronic GVHD, are similar to our previous experience with higher doses of PTCY. Two-year overall survival and relapse-free survival were 77.1% and 58.3%. There were low incidences of infections and only one early cardiac event. These results suggest that reduced-dose PTCY provides adequate immunosuppression with a low toxicity profile. PTCY 50 mg/kg/day on days +3/+4 is an excellent strategy to prevent GVHD. However, its use is associated with adverse outcomes such as delayed engraftment, increased risk of infection, and cardiac complications. This pilot study evaluates the efficacy and toxicity of a reduced dose of PTCY (40 mg/kg/day) combined with tacrolimus in 22 peripheral blood HLA-matched alloHSCT patients. At day +100, the cumulative incidences of grade II–IV and III–IV acute GVHD were 18.2% and 4.5%, respectively. No grade IV acute GVHD or steroid-refractory disease was observed. The cumulative incidences of all-grade and moderate-severe chronic GVHD at 1-year were 11.4% and 6.4%, respectively. No patient died from transplant-related complications. Two-year OS and RFS were 77.1% and 58.3%, respectively. All patients engrafted, with neutrophil and platelet recovery occurring at a median of 15 (IQR 14–16) and 16 days (IQR 12–23), respectively. The cumulative incidences of bloodstream bacterial infections, polyomavirus BK hemorrhagic cystitis, HHV6 reactivation, CMV reactivation, and fungal infections were 13.6%, 9.1%, 9.1%, 4.6%, and 6%, respectively. Only one early cardiac event was observed. These results suggest that PTCY 40 mg/kg/day on a +3/+4 schedule provides adequate immunosuppression to allow for engraftment and prevent clinically significant GVHD with a low toxicity profile. [ABSTRACT FROM AUTHOR]

Simple Summary: In the realm of next-generation imaging, whole-body MRI (WB-MRI) is evolving as a key player in the modern management of patients with prostate cancer, showing great potential in the initial staging of high-risk disease, post-treatment evaluation, and recurrence assessment. This technique showcases both notable agreement and complementarity with PET/CT, particularly in identifying secondary bone, nodal, and visceral lesions. WB-MRI's strength lies in its "one size fits all" nature, avoiding contrast agents and radiotracers and adapting to diverse patient needs. Leveraging DWI and rFF%, it excels in bone metastasis detection, offering a comprehensive view. With promising potential for precise response assessment, WB-MRI emerges as a transformative tool in the management of metastatic prostate cancer. Prostate cancer ranks among the most prevalent tumours globally. While early detection reduces the likelihood of metastasis, managing advanced cases poses challenges in diagnosis and treatment. Current international guidelines support the concurrent use of 99Tc-Bone Scintigraphy and Contrast-Enhanced Chest and Abdomen CT for the staging of metastatic disease and response assessment. However, emerging evidence underscores the superiority of next-generation imaging techniques including PSMA-PET/CT and whole-body MRI (WB-MRI). This review explores the relevant scientific literature on the role of WB-MRI in metastatic prostate cancer. This multiparametric imaging technique, combining the high anatomical resolution of standard MRI sequences with functional sequences such as diffusion-weighted imaging (DWI) and bone marrow relative fat fraction (rFF%) has proved effective in comprehensive patient assessment, evaluating local disease, most of the nodal involvement, bone metastases and their complications, and detecting the increasing visceral metastases in prostate cancer. It does have the advantage of avoiding the injection of contrast medium/radionuclide administration, spares the patient the exposure to ionizing radiation, and lacks the confounder of FLARE described with nuclear medicine techniques. Up-to-date literature regarding the diagnostic capabilities of WB-MRI, though still limited compared to PSMA-PET/CT, strongly supports its widespread incorporation into standard clinical practice, alongside the latest nuclear medicine techniques. [ABSTRACT FROM AUTHOR]

Simple Summary: High-risk prostate cancer is an aggressive disease, and its treatment can be complex and require the involvement of several specialists. Advances in imaging and therapies in this field can improve survival and help physicians choose the best personalized approach that maintains quality of life. This article summarizes the most recent publications on this condition and its treatments, aiming to provide an updated guide for managing patients with prostate cancer who experience a higher risk of progression and death. The management of high-risk prostate cancer (PCa) presents a significant clinical challenge, often necessitating treatment intensification due to the potential presence of micrometastases. While radical prostatectomy (RP) constitutes one of the primary treatment modalities, the integration of neoadjuvant and adjuvant therapies suggests a paradigm shift towards more aggressive treatment strategies, also guided by new imaging modalities like positron emission tomography using prostate-specific membrane antigen (PSMA-PET). Despite the benefits, treatment intensification raises concerns regarding increased side effects. This review synthesizes the latest evidence on perioperative treatment intensification and de-escalation for high-risk localized and locally advanced PCa patients eligible for surgery. Through a non-systematic literature review conducted via PubMed, Scopus, Web of Science, and ClinicalTrials.gov, we explored various dimensions of perioperative treatments, including neoadjuvant systemic therapies, adjuvant therapies, and the role of novel diagnostic technologies. Emerging evidence provides more support for neoadjuvant systemic therapies. Preliminary results from studies suggest the potential for treatments traditionally reserved for metastatic PCa to show apparent benefit in a non-metastatic setting. The role of adjuvant treatments remains debated, particularly the use of androgen deprivation therapy (ADT) and adjuvant radiotherapy in patients at higher risk of biochemical recurrence. The potential role of radio-guided PSMA lymph node dissection emerges as a cutting-edge approach, offering a targeted method for eradicating disease with greater precision. Innovations such as artificial intelligence and machine learning are potential game-changers, offering new avenues for personalized treatment and improved prognostication. The intensification of surgical treatment in high-risk PCa patients is a dynamic and evolving field, underscored by the integration of traditional and novel therapeutic approaches. As evidence continues to emerge, these strategies will refine patient selection, enhance treatment efficacy, and mitigate the risk of progression, although with an attentive consideration of the associated side effects. [ABSTRACT FROM AUTHOR]

Simple Summary: Neoadjuvant chemotherapy in breast cancer facilitates breast and axillary surgery and offers significant prognostic value. We present a retrospective cohort of 482 stage II and III breast cancer patients treated with neoadjuvant chemotherapy based on anthracycline and taxans, plus antiHER2 in HER2-positive cases. The 10-year estimated disease free survival was 77.3% (95%CI 73.3–81.4%) and the Breast cancer specific survival 83.7% (95%CI 80.3–87.2%). The statistically independent factors related to patient survival were pathology subtype (lobular cancers HR, 4); molecular surrogate subtype (triple negative HR, 4); type of surgery (mastectomy HR, 2), response to chemotherapy (the risk incremented according to the residual cancer burden in 2.2, 4.4 and 8.0 times in I, II and III, respectively) and vascular invasion (HR, 2.4). BRCA carriers presented a longer survival, with an estimated 10 years DDFS of 89.6% vs. 77.2% for non-carriers, p = 0.054. Long-term outcomes after neoadjuvant chemotherapy can help patients and clinicians make well-informed decisions. Introduction: Neoadjuvant chemotherapy in breast cancer offers the possibility to facilitate breast and axillary surgery; it is a test of chemosensibility in vivo with significant prognostic value and may be used to tailor adjuvant treatment according to the response. Material and Methods: A retrospective single-institution cohort of 482 stage II and III breast cancer patients treated with neoadjuvant chemotherapy based on anthracycline and taxans, plus antiHEr2 in Her2-positive cases, was studied. Survival was calculated at 5 and 10 years. Kaplan–Meier curves with a log-rank test were calculated for differences according to age, BRCA status, menopausal status, TNM, pathological and molecular surrogate subtype, 20% TIL cut-off, surgical procedure, response to chemotherapy and the presence of vascular invasion. Results: The pCR rate was 25.3% and was greater in HER2 (51.3%) and TNBC (31.7%) and in BRCA carriers (41.9%). The factors independently related to patient survival were pathology and molecular surrogate subtype, type of surgery, response to NACT and vascular invasion. BRCA status was a protective prognostic factor without reaching statistical significance, with an HR 0.5 (95%CI 0.1–1.4). Mastectomy presented a double risk of distant recurrence compared to breast-conservative surgery (BCS), supporting BCS as a safe option after NACT. After a mean follow-up of 126 (SD 43) months, luminal tumors presented a substantial difference in survival rates calculated at 5 or 10 years (81.2% compared to 74.7%), whereas that for TNBC was 75.3 and 73.5, respectively. The greatest difference was seen according to the response in patients with pCR, who exhibited a 10 years DDFS of 95.5% vs. 72.4% for those patients without pCR, p < 0001. This difference was especially meaningful in TNBC: the 10 years DDFS according to an RCB of 0 to 3 was 100%, 80.6%, 69% and 49.2%, respectively, p < 0001. Patients with a particularly poor prognosis were those with lobular carcinomas, with a 10 years DDFS of 42.9% vs. 79.7% for ductal carcinomas, p = 0.001, and patients with vascular invasion at the surgical specimen, with a 10 years DDFS of 59.2% vs. 83.6% for those patients without vascular invasion, p < 0.001. Remarkably, BRCA carriers presented a longer survival, with an estimated 10 years DDFS of 89.6% vs. 77.2% for non-carriers, p = 0.054. Conclusions: Long-term outcomes after neoadjuvant chemotherapy can help patients and clinicians make well-informed decisions. [ABSTRACT FROM AUTHOR]

Simple Summary: Cachexia occurs in up to 80% of patients with cancer. Although cancer-associated cachexia dramatically decreases overall survival and quality of life, it is often overlooked. To make meaningful progress in identifying cancer cachexia earlier and finding treatments for this condition, Moffitt Cancer Center held its first Cachexia Working Group Retreat in 2022. This manuscript describes the priorities discussed at the retreat and highlights collaborations that arose afterward. For many patients, the cancer continuum includes a syndrome known as cancer-associated cachexia (CAC), which encompasses the unintended loss of body weight and muscle mass, and is often associated with fat loss, decreased appetite, lower tolerance and poorer response to treatment, poor quality of life, and reduced survival. Unfortunately, there are no effective therapeutic interventions to completely reverse cancer cachexia and no FDA-approved pharmacologic agents; hence, new approaches are urgently needed. In May of 2022, researchers and clinicians from Moffitt Cancer Center held an inaugural retreat on CAC that aimed to review the state of the science, identify knowledge gaps and research priorities, and foster transdisciplinary collaborative research projects. This review summarizes research priorities that emerged from the retreat, examples of ongoing collaborations, and opportunities to move science forward. The highest priorities identified include the need to (1) evaluate patient-reported outcome (PRO) measures obtained in clinical practice and assess their use in improving CAC-related outcomes; (2) identify biomarkers (imaging, molecular, and/or behavioral) and novel analytic approaches to accurately predict the early onset of CAC and its progression; and (3) develop and test interventions (pharmacologic, nutritional, exercise-based, and through mathematical modeling) to prevent CAC progression and improve associated symptoms and outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Is the resection of spinal meningiomas in asymptomatic patients or patients with mild neurological symptoms justified? In this study, we compare the neurological outcome, quality of life, and quality of care of these patients to patients with more severe neurological symptoms. The results show that early neurosurgical intervention leads to better neurological outcomes and quality of life, contradicting a watch-and-see regime. Background: The main treatment modality for spinal meningiomas (SM) is gross total resection (GTR). However, the optimal timing of surgery, especially in cases with absent or mild neurological symptoms, remains unclear. The aim of this study is to assess the impact of early-stage resection on neurological outcome, quality of life (QoL), and quality of care. The primary objective is a favorable neurological outcome (McCormick scale 1). Methods: We retrospectively analyzed data from patients who underwent operations for SM between 2011 and 2021. Patients with mild neurological symptoms preoperatively (McCormick scale 1 and 2) were compared to those with more severe neurological symptoms (McCormick scale 3–5). Disabilities and QoL were assessed according to validated questionnaires (SF-36, ODI, NDI). Results: Age, spinal cord edema, thoracic localization, and spinal canal occupancy ratio were associated with more severe neurological symptoms (all p < 0.05). Patients presenting with mild symptoms were associated with favorable neurological outcomes (OR: 14.778 (95%CI 3.918–55.746, p < 0.001)), which is associated with shorter hospitalization, better QoL, and fewer disabilities (p < 0.05). Quality of care was comparable in both cohorts. Conclusions: Early surgical intervention for SM, before the development of severe neurological deficits, should be considered as it is associated with a favorable neurological outcome and quality of life. [ABSTRACT FROM AUTHOR]

Simple Summary: Estimating the risk of postoperative complications is important for shared decision-making with the patient. This also helps multidisciplinary teams to plan preoperative management and postoperative care and predict duration of recovery. In this retrospective pilot study, we aim to evaluate the accuracy and reliability of the P-POSSUM and ACS-NSQIP surgical risk calculators in predicting postoperative complications in gynaecological–oncological (GO) robotic surgery (RS). We were able to demonstrate that the ACS-NSQIP risk tool showed 90% accuracy in prediction of five major complications and mortality. Purpose: In this retrospective pilot study, we aim to evaluate the accuracy and reliability of the P-POSSUM and ACS-NSQIP surgical risk calculators in predicting postoperative complications in gynaecological–oncological (GO) robotic surgery (RS). Methods: Retrospective data collection undertaken through a dedicated GO database and patient notes at a tertiary referral cancer centre. Following data lock with the actual post-op event/complication, the risk calculators were used to measure predictive scores for each patient. Baseline analysis of 153 patients, based on statistician advice, was undertaken to evaluate P-POSSUM and ACS-NSQIP validity and relevance in GO patients undergoing RS performed. Results: P-POSSUM reports on mortality and morbidity only; ACS-NSQIP reports some individual complications as well. ACS-NSQIP risk prediction was most accurate for venous thromboembolism (VTE) (area under the curve (AUC)-0.793) and pneumonia (AUC-0.657) and it showed 90% accuracy in prediction of five major complications (Brier score 0.01). Morbidity was much better predicted by ACS-NSQIP than by P-POSSUM (AUC-0.608 vs. AUC-0.551) with the same result in mortality prediction (Brier score 0.0000). Moreover, a statistically significant overestimation of morbidity has been shown by the P-POSSUM calculator (p = 0.018). Conclusions: Despite the limitations of this pilot study, the ACS-NSQIP risk calculator appears to be a better predictor of major complications and mortality, making it suitable for use by GO surgeons as an informed consent tool. Larger data collection and analyses are ongoing to validate this further. [ABSTRACT FROM AUTHOR]

Simple Summary: Sorafenib has been the standard of care for advanced hepatocellular carcinoma (aHCC) patients since 2008. Recently, new therapies have been funded that provide increased survival in this patient population. The aim of our retrospective cohort study of linked administrative databases in Ontario was to understand the characteristics of patients with aHCC, their treatment patterns, survival outcomes, healthcare resource utilization (HCRU), and costs. We observed that patients who received systemic therapy for aHCC had a higher median overall survival (mOS) from diagnosis compared to patients who received other systemic therapies or a locoregional treatment (LRT). The mean cost per patient was $52,166 CAD for all the patients in the study, with inpatient hospitalizations and oral medications as the largest cost drivers. The therapeutic landscape for aHCC has evolved in recent years, necessitating a comprehensive analysis of treatment patterns, clinical outcomes, HCRU, and costs to contextualize emerging treatments. This study aimed to investigate these outcomes using real-world data from Ontario, Canada. This retrospective cohort study was conducted using linked administrative databases from April 2010 to March 2020. Patients diagnosed with aHCC were included, and their clinical and demographic characteristics were analyzed, as well as treatment patterns, survival, HCRU, and economic burden. Among 7322 identified patients, 802 aHCC patients met the eligibility criteria for inclusion in the study. Treatment subgroups included 1L systemic therapy (53.2%), other systemic treatments (4.5%), LRT (9.0%), and no treatment (33.3%). The median age was 66 years, and the majority were male (82%). The mOS for the entire cohort from diagnosis was 6.5 months. However, patients who received 1L systemic therapy had an mOS of 9.0 months, which was significantly higher than the other three subgroups. The mean cost per aHCC-treated patient was $49,640 CAD, with oral medications and inpatient hospitalizations as the largest cost drivers. The results underscore the need for the continuous evaluation and optimization of HCC management strategies in the era of evolving therapeutic options. [ABSTRACT FROM AUTHOR]

Simple Summary: Gorlin syndrome (GS) is a genetic disorder characterized by multiple basal cell carcinomas (BCCs) due to mutations in the hedgehog signaling pathway. Patients with GS may need dozens or even hundreds of surgical procedures in their lifetime, which can leave them severely scarred, deformed, and disfigured. In 16 patients with GS, we examined the effectiveness, safety, and length of response to oral hedgehog inhibitors. According to our retrospective study, sonidegib inhibited the growth of both newly diagnosed and pre-existing basal cell carcinomas more successfully and safely than vismodegib. Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome (GS), is a genetic disorder characterized by the development of multiple cutaneous BCCs due to mutations in the hedgehog signaling pathway. The use of hedgehog pathway inhibitors—vismodegib and sonidegib—has emerged as a promising therapeutic strategy for managing BCCs in individuals with GS. In a retrospective study conducted between March 2012 and January 2024, a cohort of 16 Gorlin syndrome patients who received treatment with either sonidegib or vismodegib were analyzed. The primary objectives of the study were to evaluate the efficacy, safety profile, and duration of response to oral hedgehog inhibitors in this patient population. The study assessed various parameters, including the number of new BCCs that developed before and after treatment initiation, the duration and sustainability of treatment responses, as well as the incidence of adverse effects associated with hedgehog inhibitor therapy. The findings of the study revealed that sustained treatment with hedgehog inhibitors could effectively suppress the progression of both new and existing BCCs. Furthermore, the results indicated that sonidegib exhibited superior efficacy and safety compared to vismodegib in the treatment of BCCs in individuals with GS. Notably, adjustments to the administration schedule of sonidegib were found to improve tolerability without compromising therapeutic efficacy, potentially leading to prolonged durations of treatment response and disease control. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to explore the relationship of the pN stage of thyroid cancer (TC) and ultrasound hypoechogenicity with encapsulation and vascular invasion. A retrospective study involving 678 TC patients revealed that a greater pN stage was correlated with encapsulation and vascular invasion as well as with positive hypoechogenicity. These findings have significant prognostic and clinical implications for managing TC. Discovering these correlations confirms the importance of the TNM scale in stratifying TC patients based on disease severity. The results suggest that the hypoechoic patterns observed on thyroid ultrasound may serve as indicators of aggressive tumour behaviour and increased invasion risk. This analysis highlights diverse invasion patterns among TC patients, which may have significant clinical implications for diagnostic processes and treatment strategy selection. Further research is necessary to validate these findings and explore new biomarkers and imaging methods to refine TC staging systems and improve TC patient care. In this retrospective study, the relationship between the pN stage of TC and the ultrasound hypoechogenicity of tumour encapsulation and vascular invasion was investigated. The data of a total of 678 TC patients were analysed. The goal of this study was to assess the significance of the pTNM score and preoperative ultrasound features in predicting cancer prognosis and guiding therapeutic decisions in patients with TC. The main research methods included a retrospective analysis of patient data, mainly the pTNM score and presence of tumour encapsulation and vascular invasion obtained from histopathological results and preoperative ultrasound imaging. Patients with well-differentiated TCs (papillary and follicular) were extracted from TC patients to better unify the results because of similar clinical strategies for these TCs. Significant associations were observed between advanced pN stage and the presence of encapsulation and vessel invasion. The majority of pN1a patients exhibited encapsulation (77.71%; p < 0.0001) and vascular invasion (75.30%; p < 0.0001), as did the majority of pN1b patients (100%; p < 0.0001 and 100%; p < 0.0001, respectively). Less than half of the patients with hypoeghogenic patterns presented with encapsulation (43.30%; p < 0.0001) and vascular invasion (43.52%; p < 0.0001), while the vast majority of patients without hypoechogenicity did not present with encapsulation (90.97%; p < 0.0001) or vascular invasion (90.97%; p < 0.0001). Hypoechogenicity was found to be indicative of aggressive tumour behaviour. The results of this study underscore the importance of accurate N staging in TC and suggests the potential use of ultrasound features in predicting tumour behaviour. Further research is needed to confirm these findings and explore additional prognostic markers to streamline TC management strategies and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains an effective treatment modality in many hematological malignancies. Few studies directly compare rabbit anti-thymocyte globulin (r-ATG) formulations Thymoglobuline (ATG-T) and Grafalon (ATG-G). Our retrospective analysis compared the outcomes in 87 adult allo-HCT patients receiving ATG-T or ATG-G. No significant differences were found in acute graft-versus-host disease (aGvHD) incidence. However, chronic GvHD (cGvHD) was less common with ATG-T (7.5% vs. 38.3%, p = 0.001). ATG-T patients had higher cytomegalovirus (CMV) reactivation rates (70% vs. 31.9%, p < 0.001) and a shorter time to CMV (<61 days, 77.8% vs. 33.3%, p = 0.008), but were mostly asymptomatic (85.7% vs. 43.8%, p = 0.005). Overall survival (OS) and relapse-free survival (RFS) at 5 and 3 years, respectively, showed no significant differences between ATG-T and ATG-G (32.0% vs. 40.3%, p = 0.423; 66.7% vs. 60.4%, p = 0.544). Despite notable advancements in immunotherapy in the past decades, allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a promising, potentially curative treatment modality. Only a limited number of studies have performed a direct comparison of two prevalent rabbit anti-thymocyte globulin (r-ATG) formulations—specifically, Thymoglobuline (ATG-T, formerly Genzyme) and Grafalon (ATG-G, formerly Fresenius). The primary objective of our retrospective analysis was to compare the outcomes of adult patients undergoing matched or mismatched unrelated donor (MUD/MMUD) allo-HCT, with a graft-versus-host disease (GvHD) prophylaxis based on either ATG-T or ATG-G. A total of 87 patients who had undergone allo-HCT between 2012 and 2022 were included. We observed no significant differences between ATG-T and ATG-G concerning the occurrence of acute graft-versus-host disease (aGvHD), regardless of its severity. Conversely, chronic graft-versus-host disease (cGvHD) occurred less frequently in the ATG-T group compared to the ATG-G group (7.5% vs. 38.3%, p = 0.001). The negative impact of ATG-G on cGvHD was confirmed by multivariate analysis (HR 8.12, 95% CI 2.06–32.0, p = 0.003). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, p < 0.001), with a shorter time between transplant and CMV (<61 days, 77.8% vs. 33.3%, p = 0.008) and a higher median CMV copy number (1000 vs. 0, p = 0.004). Notably, despite a higher occurrence of CMV reactivations in the ATG-T cohort, most patients were asymptomatic compared to ATG-G (85.7% vs. 43.8%, p = 0.005). By multivariate analysis, only aGvHD had an influence on CMV reactivations (HR 0.18, 95% CI 0.04–0.75, p = 0.019). Finally, we observed no significant differences in terms of 5-year overall survival (OS) and 3-year relapse-free survival (RFS) while comparing ATG-T and ATG-G (32.0% vs. 40.3%, p = 0.423; 66.7% vs. 60.4%, p = 0.544, respectively). [ABSTRACT FROM AUTHOR]

Simple Summary: Corticosteroid use for the treatment of immune related adverse events (irAEs) after immune checkpoint inhibitor (ICI) use comes with concerns of side effects and the potential abrogation of antitumor immunity. Relatedly, the impact of steroid-sparing immunosuppressive agents (SSIAs) for treatment of irAEs on tumor outcomes is not well known, and current literature on this topic is limited by study design and issues around immortal time bias. This retrospective case-control study accounts for immortal time bias via strategic statistical methodology. Our results suggest that SSIAs used for irAE treatment may not negatively impact cancer outcomes in malignant melanoma and non-small cell lung cancer. For patients with melanoma, our results demonstrated better progression free survival for patients treated with infliximab compared to patients treated with corticosteroid monotherapy for irAEs. This study supports the safety for utilizing SSIAs for irAE treatment in patients receiving immune checkpoint inhibitors. Our study also encourages accounting for immortal time bias in the design of other observational studies in this space to accurately convey results and draw clinically meaningful conclusions. Background: The effects of steroid-sparing immunosuppressive agents (SSIAs), used for the treatment of immune-related adverse events (irAEs), on immune checkpoint inhibitor (ICI) antitumor activity is not well known. We compared tumor outcomes of patients who received corticosteroid monotherapy (CS) versus a corticosteroid plus SSIA (CS-SSIA) for irAE treatment, using statistical methods to address immortal time bias. Methods: We conducted a retrospective case-control study on patients ≥ 18 years with melanoma or non-small-cell lung cancer (NSCLC) treated with ≥1 ICI at a quaternary care center between 1 January 2016 and 11 January 2021. Patients were divided into two cohorts: CS or CS-SSIA. We used propensity score nearest-neighbor matching to match on tumor type, stage, and prior lines of therapy. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included the time from the start of the irAE treatment to the irAE resolution. Hazard ratios (HRs) for PFS and OS were calculated using the Cox proportional hazard regression method with both (1) the time to the steroid and SSIA as time-varying covariates and (2) a binary exposure classification not accounting for the time to the treatment. Results: A total of 167 patients were included after matching (132 in the CS cohort and 35 in the CS-SSIA cohort). Sixty-six percent of all the patients had melanoma. The most common irAEs requiring treatment were gastroenterocolitis and hepatitis. In an adjusted analysis not accounting for immortal time bias, there were no significant differences in PFS (HR 0.75, 95% CI [0.46–1.23]) or OS (HR 0.82, 95% CI [0.46–1.47]). In analyses using a time-varying treatment indicator, there was a trend toward improved PFS in patients treated with SSIAs (HR 0.54, CI 0.26–1.10). There was no difference in OS (HR 1.11, CI 0.55–2.23). Patients with melanoma who specifically received infliximab had improved PFS compared to patients with CS only, after adjusting for immortal time bias (HR 0.32, CI 0.24–0.43). Conclusions: The use of SSIAs with CS did not have worse outcomes than CS monotherapy. In melanoma, our findings showed improved PFS for the use of infliximab versus steroid monotherapy for irAEs. Large, prospective, randomized controlled trials are needed to confirm these findings and guide the optimal treatment of irAEs. [ABSTRACT FROM AUTHOR]

Simple Summary: In patients with high-risk prostate cancer (HRPC) after radical prostatectomy, biochemical recurrence increases the risk of distant metastasis. Therefore, complementary prognostic biomarkers are required to identify the subpopulation of patients with HRPC who develop clinical recurrence after biochemical recurrence. This study was performed to identify prognostic factors for clinical recurrence in patients with HRPC who experience biochemical recurrence by conducting an analysis of the expression levels of snRNAs in formalin-fixed paraffin-embedded (FFPE) radical prostatectomy samples. The FFPE sample-derived snRNA RNU1-1/RNU1-2 could serve as an independent prognostic factor of clinical recurrence-free survival after biochemical recurrence of HRPC cases where known prognostic factors (e.g., Gleason score) cannot distinguish between patients with clinical and non-clinical recurrence. Thus, snRNAs associated with prostate cancer may assist the early detection of clinical recurrence in patients with HRPC, allowing for more tailored and restorative treatments. In patients with high-risk prostate cancer (HRPC) after radical prostatectomy (RP), biochemical recurrence (BCR) increases the risk of distant metastasis. Accordingly, additional prognostic biomarkers are required to identify the subpopulation of patients with HRPC who develop clinical recurrence (CR) after BCR. The objective of this study was to identify biomarkers in formalin-fixed paraffin-embedded (FFPE) RP samples that are prognostic for CR in patients with HRPC who experience BCR after RP (post-RP BCR). First, we performed a preliminary RNA sequencing analysis to comprehensively profile RNA expression in FFPE RP samples obtained from patients with HRPC who developed CR after post-RP BCR and found that many snRNAs were very abundant in preserved FFPE samples. Subsequently, we used quantitative polymerase chain reaction (qPCR) to compare the expression levels of highly abundant snRNAs in FFPE RP samples from patients with HRPC with and without CR after post-RP BCR (21 CR patients and 46 non-CR patients who had more than 5 years of follow-up after BCR). The qPCR analysis revealed that the expression levels of snRNA RNU1-1/1-2 and RNU4-1 were significantly higher in patients with CR than in patients without CR. These snRNAs were significantly correlated with clinical recurrence-free survival (RFS) in patients with HRPC who experienced post-RP BCR. Furthermore, snRNA RNU1-1/1-2 could serve as an independent prognostic factor for clinical RFS in post-RP BCR of HRPC cases where known prognostic factors (e.g., Gleason score) cannot distinguish between CR and non-CR patients. Our findings provide new insights into the involvement of snRNAs in prostate cancer progression. [ABSTRACT FROM AUTHOR]