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Simple Summary: Achieving improved rates of overall survival remains a significant challenge in advanced-stage ovarian cancer; even if complete debulking is achieved, certain patients report poor results in terms of survival. Therefore, the aim of this paper is to investigate new prognostic markers that could point out which cases could benefit most from debulking surgery and which ones should be rather submitted to neoadjuvant therapies followed by debulking surgery. Background: Despite improving surgical techniques and achieving more often complete debulking procedures, certain patients with advanced-stage ovarian cancer still have a very poor prognosis. The aim of the current paper is to investigate whether inflammatory and nutritional status can predict the long-term outcomes of ovarian cancer patients. Methods: A retrospective analysis of 57 cases diagnosed with advanced-stage ovarian cancer submitted to surgery as first intent therapy was carried out. In all cases, the preoperative status was determined by calculating the CRP/albumin ratio, as well as the Glasgow score, the modified Glasgow score and the prognostic nutritional index. Results: Patients presenting higher values of the CRP/albumin ratio, with a higher Glasgow score, modified Glasgow score and prognostic nutritional index (PNI), were more frequently associated with incomplete debulking surgery, a higher peritoneal carcinomatosis index and poorer overall survival (20 months versus 9 months for the CRP/albumin ratio p = 0.011, 42 versus 27 versus 12 months for the Glasgow score p = 0.042, 50 versus 19 versus 12 months for the modified Glasgow score, p = 0.001, and 54 months versus 21 months, p = 0.011 for the prognostic nutritional index). Conclusions: A strong relationship between the nutritional and inflammatory status in advanced-stage ovarian cancer seems to exist. [ABSTRACT FROM AUTHOR]

Simple Summary: Uveal melanoma (UM) is a rare type of cancer of the eye that develops from a cell type called melanocytes, which are present in the uveal tract. These patients have a high risk of liver metastasis, usually many years after the initial diagnosis, which is life threatening. We discovered a population of cells in the primary tumor called dual-nature hybrid cells (DNCs) similar to previously discovered cells in the blood (i.e., circulating hybrid cells, CHCs) with shared characteristics of both cancer cells and white blood cells. In this paper, we determined the types of white blood cells capable of participating in the formation of a hybrid cell with a cancer cell, and we re-created these DNCs in a cell culture. The study of the cells of this tumor, particularly DNCs, is crucial to better understanding dissemination and uncovering a possible target for treatment of this systemic disease. Background: Metastasis, occurring years after primary diagnosis, represents a poor prognosis in uveal melanoma (UM)-affected individuals. The nature of cells involved in this process is under debate. Circulating hybrid cells that have combined tumor and immune cell features found in blood were predictive of metastasis and may correspond to dual-nature cells (DNC) in the primary tumor. Herein, we sought to determine the presence of DNCs in primary UM tumors, the cell types involved in their genesis, and their ability to be formed in vitro. Methods: UM lesions (n = 38) were immunolabeled with HMB45 in combination with immune-cell-specific antibodies. In parallel, we co-cultured UM cells and peripheral blood mononuclear cells (PBMCs) to analyze DNC formation. Results: HMB45+/CD45+ DNCs were present in 90% (26/29) of the tumors, HMB45+/CD8+ DNCs were present in 93% (26/28), and HMB45+/CD68+ DNCs were present in 71% (17/24). DNCs formed with CD8+ and CD68+ cells were positively correlated to the infiltration of their respective immune cells. Notably, UM cells were prone to hybridize with PBMCs in vitro. Conclusions: This phenotypical characterization of DNCs in UM demonstrates that CD8+ T-cells and macrophages are capable of DNC formation, and they are important for better understanding metastatic dissemination, thus paving the path towards novel therapeutic avenues. [ABSTRACT FROM AUTHOR]

Simple Summary: Vacuum-assisted breast biopsy (VABB) represents one of the best instruments for radiologists to obtain a histological diagnosis of suspicious lesions on imaging. The advent of digital breast tomosynthesis (DBT)-guided VABB has increased the accuracy of diagnosis in the most complex lesions, particularly those without ultrasound correlation or those visible only on DBT. In this paper, we retrospectively analyzed our experience with VABB. Starting from a review of the literature, we evaluated the challenges arising from clinical practice to provide useful indications for the implementation of this technique. We identified 37 breast cancers at an early stage with a low complication rate and high histopathological concordance between VABB and surgery. Compared to the literature, our results confirmed the fundamental role of DBT-VABB in achieving a timely diagnosis for nonpalpable lesions, offering a safe and minimally invasive approach when the technique is executed correctly. Vacuum-assisted breast biopsy (VABB) guided by digital breast tomosynthesis (DBT) represents one of the best instruments to obtain a histological diagnosis of suspicious lesions with no ultrasound correlation or those which are visible only on DBT. After a review of the literature, we retrospectively analyzed the DBT-guided VABBs performed from 2019 to 2022 at our department. Descriptive statistics, Pearson's correlation and χ2 test were used to compare distributions of age, breast density (BD) and early performance measures including histopathology. We used kappa statistics to evaluate the agreement between histological assessment and diagnosis. Finally, we compared our experience to the literature to provide indications for clinical practice. We included 85 women aged 41–84 years old. We identified 37 breast cancers (BC), 26 stage 0 and 11 stage IA. 67.5% of BC was diagnosed in women with high BD. The agreement between VABB and surgery was 0.92 (k value, 95% CI: 0.76–1.08). We found a statistically significant inverse correlation between age and BD. The post-procedural clip was correctly positioned in 88.2%. The post-procedural hematoma rate was 14.1%. No infection or hemorrhage were recorded. When executed correctly, DBT-guided VABB represents a safe and minimally invasive technique with high histopathological concordance, for detecting nonpalpable lesions without ultrasound correlation. [ABSTRACT FROM AUTHOR]

Simple Summary: Measurable residual disease monitoring is an important prognostic tool in haematological malignancies commonly performed by two modalities: flow cytometry and molecular methods. In this paper, we studied consecutive adult participants requiring flow cytometric measurable residual disease monitoring. This is one of the largest prospective Australian studies to date, providing a unique insight into the Australian context. We described five distinctive patterns associated with disease relapse and survival and also investigated correlation with molecular methods. Our results provide additional evidence that the correlation between molecular and flow cytometric methods is moderate in B-lymphoblastic leukaemia and poor in acute myeloid leukaemia. There was a strong association between flow cytometry results and relapse in acute myeloid leukaemia but less so for B-lymphoblastic leukaemia. Our novel data indicate that the pattern of change in measurable residual disease over time was associated with the risk of relapse, particularly in acute myeloid leukaemia and highlight the divergent ways measurable residual disease testing can be employed across different leukaemias. Measurable residual disease (MRD) detected by flow cytometry (FC) is well established in paediatric B- lymphoblastic leukaemia (B-ALL) and adult chronic lymphocytic leukaemia (CLL), but its utility in adult B-ALL and adult acute myeloid leukaemia (AML) is less clear. In this prospective MRD study, one of the largest in Australia to date, we examined consecutive bone marrow aspirates from adult participants with B-ALL (n = 47) and AML (n = 87) sent for FC-MRD testing at a quaternary referral hospital in Sydney. FC-MRD results were correlated to corresponding Mol-MRD testing where available and clinical outcomes at three-month intervals over 1 year. B-ALL showed a moderate positive correlation (rs = 0.401, p < 0.001), while there was no correlation between FC-MRD and Mol-MRD for AML (rs = 0.13, p = 0.237). Five FC-MRD patterns were identified which had significant associations with relapse (X2(4) = 31.17(4), p > 0.001) and survival (X2(4) = 13.67, p = 0.008) in AML, but not in B-ALL. The three-month MRD results were also strongly associated with survival in AML, while the association in B-ALL was less evident. There was a moderate correlation between FC-MRD and Mol-MRD in B-ALL but not AML. The association of FC-MRD with relapse and survival was stronger in AML than in B-ALL. Overall, these findings suggest divergent utilities of FC-MRD in AML and B-ALL. [ABSTRACT FROM AUTHOR]

Simple Summary: Since the introduction of effective systemic therapies (ESTs) (in the form of both targeted and immuno-based therapies) in the treatment of malignant melanoma, the prognosis of metastatic patients has dramatically changed. The role of metastasectomy in oligometastatic patients has rarely been addressed in this new pharmacological era. Even though lungs represent the most frequent site of melanoma metastases, only limited data are available on the role of surgery in isolated pulmonary metastases from malignant melanoma (PmMM). In this study, we describe the outcomes of patients who underwent metastasectomy of PmMM in the era of ESTs, and identified prognostic factors affecting survival in our multicentric experience. To the best of our knowledge, this is the first paper analyzing in detail the impact of metastasectomy of PmMM in the era of ESTs. In the last decade, the emergence of effective systemic therapies (ESTs) in the form of both targeted and immuno-based therapies has revolutionized the treatment of patients with advanced stage III and stage IV melanoma. Even though lungs represent the most frequent site of melanoma metastases, only limited data are available on the role of surgery in isolated pulmonary metastases from malignant melanoma (PmMM) in the era of ESTs. The aim of this study is to describe the outcomes of patients who underwent metastasectomy of PmMM in the era of ESTs, in order to identify prognostic factors affecting survival and to provide a framework for more informed patient selection of treatmeant with lung surgery in the future. Clinical data of 183 patients who underwent metastasectomy of PmMM between June 2008 and June 2021 were collected among four Italian Thoracic Centers. The main clinical, surgical and oncological variables reviewed were: sex, comorbidities, previous oncological history, melanoma histotypes and primary site, date of primary cancer surgical treatment, melanoma growth phase, Breslow thickness, mutation pattern disease, stage at diagnosis, metastatic sites, DFI (Disease Free Interval), characteristics of lung metastases (number, side, dimension, type of resection), adjuvant therapy after lung metastasectomy, site of recurrence, disease-free survival (DFS) and cancer-specific survival (CSS; defined as the time interval between the first melanoma resection or lung metastasectomy and death from cancer). All patients underwent surgical resection of the primary melanoma before lung metastasectomy. Twenty-six (14.2%) patients already had a synchronous lung metastasis at the time of primary melanoma diagnosis. A wedge resection was performed in 95.6% of cases to radically remove the pulmonary localizations, while an anatomical resection was necessary in the remaining cases. The incidence of major post-operative complications was null, while only 21 patients (11.5%) developed minor complications (mainly air leakage followed by atrial fibrillation). The mean in-hospital stay was 4.46 ± 2.8 days. Thirty- and sixty-day mortality were null. After lung surgery, 89.6% of the population underwent adjuvant treatments (47.0% immunotherapy, 42.6% targeted therapy). During a mean FUP of 107.2 ± 82.3 months, 69 (37.7%) patients died from melanoma disease, 11 (6.0%) from other causes. Seventy-three patients (39.9%) developed a recurrence of disease. Twenty-four (13.1%) patients developed extrapulmonary metastases after pulmonary metastasectomy. The CSS from melanoma resection was: 85% at 5 years, 71% at 10 years, 54% at 15 years, 42% at 20 years and 2% at 25 years. The 5- and 10-year CSS from lung metastasectomy were 71% and 26%, respectively. Prognostic factors negatively affecting CSS from lung metastasectomy at multivariable analysis were: melanoma vertical growth (p = 0.018), previous metastatic sites other than lung (p < 0.001) and DFI < 24 months (p = 0.007). Our results support the evidence that surgical indication confirms its important role in stage IV melanoma with resectable pulmonary metastases, and selected patients can still benefit from pulmonary metastasectomy in terms of overall cancer specific survival. Furthermore, the novel systemic therapies may contribute to prolonged survival after systemic recurrence following pulmonary metastasectomy. Patients with long DFI, radial growth melanoma phase and no site of metastatization other than lung seem to be the best candidate cases for lung metastasectomy; however, to drive stronger conclusions, further studies evaluating the role of metastasectomy in patients with iPmMM are needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Lymphedema affecting the breast can develop after breast cancer treatment. Currently breast lymphedema isn't well recognised nor techniques to measure lymphedema affecting the breast as well studied. This paper explores the validity and reliability of measures which can be used to determine the presence of breast lymphedema. Women with and without breast lymphedema were included in this study to enable comparisons to be made. Improving the assessment of breast lymphedema will advance clinical practice and enable the outcome of treatment to be reported. Ultrasound and tissue dielectric constant were found to be able to reliably distinguish between edema and non edematous breast tissue. In addition certain patient characteristics and breast caner treatments were found to associated with the development of breast lymphedema. Lymphedema can develop after treatment for breast cancer (BCRL). Lymphedema of the breast is not well studied. Currently, the main techniques used to diagnose and monitor the effectiveness of treatment are subjective clinician assessment and patient reports. Eighty-nine women who had undergone breast cancer treatment were recruited with and without breast lymphedema. Blinded clinical assessment determined the presence or absence of breast lymphedema. Measurement of skin thickness by ultrasound scanning, local tissue water by tissue dielectric constant (TDC) and tissue indentation by tonometry was recorded. Breast cancer treatment and demographic details were documented. Descriptive statistics were undertaken to compare sample characteristics, including the Chi-squared test, Odds Ratio (OR) and Relative Risks (RR) calculated. Increased body mass index (BMI), larger bra size, increased number of positive lymph nodes, axillary surgery, chemotherapy and increased Nottingham Prognostic Index (NPI) were all associated with breast lymphedema (p < 0.05). Ultrasound and TDC measurements were significantly higher in the lymphedema group (p < 0.05). Receiver Operator Characteristic (ROC) curves demonstrated that ultrasound and TDC measurements could distinguish between edematous and non-edematous breasts. Threshold levels were produced, which demonstrated good levels of sensitivity and specificity. These findings have the potential to improve the diagnosis of breast lymphedema. [ABSTRACT FROM AUTHOR]

Simple Summary: Papillary thyroid cancer is not an aggressive cancer, even when metastasis are present; therefore, treatment has been downgraded in recent years. However rare, mortality exists and finding the factors associated with mortality is essential and has not yet been fully accomplished; the answer probably lies in molecular factors. This study aimed to find MicroRNAs related to death in metastatic patients and found that patients who died due to progression of PTC had higher expression levels of miR-101-3p, miR-17-5p, and miR-191-5p compared with those of patients with stable metastatic disease. These findings are new in the literature and may open new doors in differentiating the patients who need more aggressive treatment from those who do not. Papillary thyroid carcinoma (PTC) is the most common neoplasm of the endocrine system and has an excellent long-term prognosis, with low rates of distant metastatic disease. Although infrequent, there are cases of deaths directly related to PTC, especially in patients with metastatic disease, and the factors that could be associated with this unfavorable outcome remain a major challenge in clinical practice. Recently, research into genetic factors associated with PTC has gained ground, especially mutations in the TERT promoter and BRAF gene. However, the role of microRNAs remains poorly studied, especially in those patients who have an unfavorable outcome at follow-up. This paper aims to evaluate molecular markers related to the different pathological processes of PTC, as well as the histological characteristics of the neoplasm, and to compare this profile with prognosis and death from the disease using an analysis of patients treated for metastatic disease in a single tertiary cancer center. Evaluation of microRNA expression in paraffin-embedded tumor specimens was carried out by quantitative PCR using the TaqMan® Low Density Array (TLDA) system. Metastatic patients who died from progression of PTC had higher expressions of miR-101-3p, miR-17-5p, and miR-191-5p when compared to patients with stable metastatic disease. These findings are of great importance but should be considered as preliminary because of the small sample. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently, nivolumab, pembrolizumab, both immune-checkpoint inhibitors (ICIs) and the combination of dabrafenib plus trametinib (D + T) were registered as adjuvant melanoma treatments, to prevent recurrence. The aim of this paper was to retrospectively review the benefits and risks of these treatments in clinical practice, by extracting data from electronic health records with a text-mining tool. In a population of 122 patients, 55 used nivolumab, 48 used pembrolizumab and 20 used D + T, and we found that the ICIs were better tolerated than D + T. However, the frequent adverse events of D + T are reversible and include pyrexia and fatigue. ICIs show immune-related chronic adverse events, and chronic thyroid-related adverse events occurred frequently. The efficacy results, including the recurrence-free survival, are promising; however, the follow-up was too short for conclusions. This study furthermore showed that the application of text-mining is a valuable method to collect data for the evaluation of adjuvant melanoma treatments. Introduction: Nivolumab (N), pembrolizumab (P), and dabrafenib plus trametinib (D + T) have been registered as adjuvant treatments for resected stage III and IV melanoma since 2018. Electronic health records (EHRs) are a real-world data source that can be used to review treatments in clinical practice. In this study, we applied EHR text-mining software to evaluate the real-world tolerability, safety, and efficacy of adjuvant melanoma treatments. Methods: Adult melanoma patients receiving adjuvant treatment between January 2019 and October 2021 at the Leiden University Medical Center, the Netherlands, were included. CTcue text-mining software (v3.1.0, CTcue B.V., Amsterdam, The Netherlands) was used to construct rule-based queries and perform context analysis for patient inclusion and data collection from structured and unstructured EHR data. Results: In total, 122 patients were included: 54 patients treated with nivolumab, 48 with pembrolizumab, and 20 with D + T. Significantly more patients discontinued treatment due to toxicity on D + T (N: 16%, P: 6%, D + T: 40%), and X2 (6, n = 122) = 14.6 and p = 0.024. Immune checkpoint inhibitors (ICIs) mainly showed immune-related treatment-limiting adverse events (AEs), and chronic thyroid-related AE occurred frequently (hyperthyroidism: N: 15%, P: 13%, hypothyroidism: N: 20%, P: 19%). Treatment-limiting toxicity from D + T was primarily a combination of reversible AEs, including pyrexia and fatigue. The 1-year recurrence-free survival was 70.3% after nivolumab, 72.4% after pembrolizumab, and 83.0% after D + T. Conclusions: Text-mining EHR is a valuable method to collect real-world data to evaluate adjuvant melanoma treatments. ICIs were better tolerated than D + T, in line with RCT results. For BRAF+ patients, physicians must weigh the higher risk of reversible treatment-limiting AEs of D + T against the risk of long-term immune-related AEs. [ABSTRACT FROM AUTHOR]

Simple Summary: Pulmonary neuroendocrine neoplasms (NENs) are a challenging type of lung cancer due to their varied clinical features and aggressive behavior. This study aimed to find specific metabolomic profiles in the blood of patients with different subtypes of lung NENs, which could help in early diagnosis. By analyzing 153 metabolites in the plasma of 120 NEN patients and comparing them with healthy individuals and patients with other lung cancers, we identified specific metabolic changes. These findings could lead to new biomarkers for early detection and better management of lung NENs, ultimately improving patient outcomes. Background/Objectives: Pulmonary neuroendocrine neoplasms (NENs) account for 20% of malignant lung tumors. Their management is challenging due to their diverse clinical features and aggressive nature. Currently, metabolomics offers a range of potential cancer biomarkers for diagnosis, monitoring tumor progression, and assessing therapeutic response. However, a specific metabolomic profile for early diagnosis of lung NENs has yet to be identified. This study aims to identify specific metabolomic profiles that can serve as biomarkers for early diagnosis of lung NENs. Methods: We measured 153 metabolites using liquid chromatography combined with mass spectrometry (LC-MS) in the plasma of 120 NEN patients and compared them with those of 71 healthy individuals. Additionally, we compared these profiles with those of 466 patients with non-small-cell lung cancers (NSCLCs) to ensure clinical relevance. Results: We identified 21 metabolites with consistently altered plasma concentrations in NENs. Compared to healthy controls, 18 metabolites were specific to carcinoid tumors, 5 to small-cell lung carcinomas (SCLCs), and 10 to large-cell neuroendocrine carcinomas (LCNECs). These findings revealed alterations in various metabolic pathways, such as fatty acid biosynthesis and beta-oxidation, the Warburg effect, and the citric acid cycle. Conclusions: Our study identified biomarker metabolites in the plasma of patients with each subtype of lung NENs and demonstrated significant alterations in several metabolic pathways. These metabolomic profiles could potentially serve as biomarkers for early diagnosis and better management of lung NENs. [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: In our study, we investigated the association between pepsin levels in bronchoalveolar lavage and factors such as hemorrhagic/non-hemorrhagic character of BAL, type of lung disease, tumor location, patient demographics, and smoking history. Our objective was to investigate the possible influence of extraesophageal reflux on the development of lung adenocarcinoma. Contrary to our hypothesis, we did not find significant differences in pepsin levels among patients with lung adenocarcinoma, pulmonary metastases, and lung sarcoidosis. Pepsin levels were even lower in lung adenocarcinoma patients after excluding hemorrhagic samples. By rigorously excluding smokers and carefully classifying patients, we minimized biases common in similar studies. However, our study was limited by small sample sizes, especially in the sarcoidosis group, and the absence of standardized thresholds for BAL pepsin as a reflux biomarker. The significance of extraesophageal reflux as a risk factor in lung adenocarcinoma has been understudied. In this study, we investigated whether extraesophageal reflux leads to higher pepsin concentrations in bronchoalveolar lavage (BAL) in patients with lung adenocarcinoma compared to controls. Subjects were recruited from non-smoker patients (lifelong non-smokers and ex-smokers with more than 5 years of non-smoking history) who had undergone bronchoscopy due to pulmonary abnormalities on a CT scan and met the inclusion criteria. Based on histological verification of the lung process, the patients were divided into three groups: (1) lung adenocarcinoma, (2) pulmonary metastases, and (3) lung sarcoidosis. Lung adenocarcinoma cases were further categorized as central or peripheral. BAL samples collected during bronchoscopy were quantitatively analyzed by enzyme-linked immunosorbent assay (ELISA) to measure pepsin levels. No statistically significant difference in pepsin concentration was observed between the lung adenocarcinoma group and control groups (p = 0.135). After excluding hemorrhagic BAL samples, the pepsin concentration was significantly the lowest in patients with lung adenocarcinoma (p = 0.023) compared to the control groups. The results of the study do not support the hypothesis of a higher occurrence of extraesophageal reflux (evaluated as the amount of pepsin in BAL) in non-smoker patients with lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) presents a significant global health challenge, necessitating advancements in early detection and treatment strategies. This study aimed to identify the serum biomarkers associated with worse survival outcomes in CRC patients, focusing on cathepsin B (CB), leukocytic elastase (LE), total sialic acid (TSA), and others. A cohort of 185 CRC patients and 35 healthy controls underwent comprehensive testing, and statistical analyses were employed to identify significant correlations. The results revealed significant associations between CB (p = 0.04), LE (p = 0.01), TSA (p = 0.008), and survival outcomes. However, no significant associations were noted for other markers. Multivariate analysis found the correlation of LE, TSA, and ATA with survival (p = 0.041). Further research is needed to validate these findings and discover additional indicators. Colorectal cancer (CRC) represents a substantial burden on global healthcare, contributing to significant morbidity and mortality worldwide. Despite advances in screening methodologies, its incidence remains high, necessitating continued efforts in early detection and treatment. Neoplastic invasion and metastasis are primary determinants of CRC lethality, emphasizing the urgency of understanding underlying mechanisms to develop effective therapeutic strategies. This study aimed to explore the potential of serum biomarkers in predicting survival outcomes in CRC patients, with a focus on cathepsin B (CB), leukocytic elastase (LE), total sialic acid (TSA), lipid-associated sialic acid (LASA), antitrypsin activity (ATA), C-reactive protein (CRP), and cystatin C (CC). We recruited 185 CRC patients and 35 healthy controls, assessing demographic variables, tumor characteristics, and 7 serum biomarker levels, including (1) CB, (2) LE, (3) TSA, (4) LASA, (5) ATA, (6) CRP, and (7) CC. Statistical analyses included ANOVA with Tukey's post hoc tests and MANOVA for continuous variables. Student's t-test was used for dependent samples, while non-parametric tests like Mann–Whitney U and Wilcoxon signed-rank tests were applied for variables deviating from the normal distribution. Categorical variables were assessed using chi-square and Kruskal-Wallis tests. Spearman's rank correlation coefficient was utilized to examine variable correlations. Survival analysis employed the Kaplan–Meier method with a log-rank test for comparing survival times between groups. Significant associations were observed between CB (p = 0.04), LE (p = 0.01), and TSA (p = 0.008) levels and survival outcomes in CRC patients. Dukes' classification stages also showed a significant correlation with survival (p = 0.001). However, no significant associations were found for LASA, ATA, CRP, and CC. Multivariate analysis of LE, TSA, and ATA demonstrated a notable correlation with survival (p = 0.041), notwithstanding ATA's lack of significance in univariate analysis (p = 0.13). CB, LE, and TSA emerged as promising diagnostic markers with prognostic value in CRC, potentially aiding in early diagnosis and treatment planning. Further research is needed to validate these findings and explore additional prognostic indicators. [ABSTRACT FROM AUTHOR]

Simple Summary: Sacrectomy represents a radical indication for bone sarcomas (e.g., osteosarcoma or chondrosarcoma) and chordomas, as well as selected carcinomas with invasion of the sacrum. Extralesional en bloc excision is surgically demanding and associated with resection-induced neurologic deficits and risks. Due to the low incidence of bone sarcomas, the rare localization in the sacrum and the complexity of the surgical procedure, studies reporting on the oncological outcome and corresponding complications in larger patient numbers are rare. The aim was to describe the oncosurgical management and the complication profile and to analyze our own treatment results after partial/total sacrectomy, with attention paid to a possible benefit by using intraoperative 3D navigation. There was a significant difference in progression-free and metastasis-free survival between sarcoma, chordoma and carcinoma patients. Complications were common, but no independently influencing causative factors could be identified. Although there was a subjective impression of improved intraoperative 3D orientation and easier identification of resection planes, the use of navigation did not significantly influence resection status or oncological patient outcome. Introduction: Bone sarcoma or direct pelvic carcinoma invasion of the sacrum represent indications for partial or total sacrectomy. The aim was to describe the oncosurgical management and complication profile and to analyze our own outcome results following sacrectomy. Methods: In a retrospective analysis, 27 patients (n = 8/10/9 sarcoma/chordoma/locally recurrent rectal cancer (LRRC)) were included. There was total sacrectomy in 9 (incl. combined L5 en bloc spondylectomy in 2), partial in 10 and hemisacrectomy in 8 patients. In 12 patients, resection was navigation-assisted. For reconstruction, an omentoplasty, VRAM-flap or spinopelvic fixation was performed in 20, 10 and 13 patients, respectively. Results: With a median follow-up (FU) of 15 months, the FU rate was 93%. R0-resection was seen in 81.5% (no significant difference using navigation), and 81.5% of patients suffered from one or more minor-to-moderate complications (especially wound-healing disorders/infection). The median overall survival was 70 months. Local recurrence occurred in 20%, while 44% developed metastases and five patients died of disease. Conclusions: Resection of sacral tumors is challenging and associated with a high complication profile. Interdisciplinary cooperation with visceral/vascular and plastic surgery is essential. In chordoma patients, systemic tumor control is favorable compared to LRRC and sarcomas. Navigation offers gain in intraoperative orientation, even if there currently seems to be no oncological benefit. Complete surgical resection offers long-term survival to patients undergoing sacrectomy for a variety of complex diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: We investigated whether the baseline plasma cell-free DNA might help to differentiate malignant nodules from benign lesions observed in screening low-dose computed tomography (LDCT) examinations. Plasma cell-free DNA was determined before the first LDCT in 137 participants in the ITALUNG trial, including 29 with screen-detected malignant nodules (17 prevalent and 12 incident) and 108 with benign nodules. In subjects with prevalent lung cancers (LC), the radiological characteristics well differentiated the malignant nodule, and the cell-free DNA was markedly increased. A total of 75% of subjects with incident LC showed a baseline cell-free DNA ≥ 3.15 ng/mL, compared to 34% of subjects with benign nodules (p = 0.006). Moreover, the cell-free DNA correlated (p = 0.001) with the tumor growth measured with nodular volume doubling time. The baseline plasma cell-free DNA is an independent, potentially useful biomarker in the LC screening process and should be further investigated. The role of total plasma cell-free DNA (cfDNA) in lung cancer (LC) screening with low-dose computed tomography (LDCT) is uncertain. We hypothesized that cfDNA could support differentiation between malignant and benign nodules observed in LDCT. The baseline cfDNA was measured in 137 subjects of the ITALUNG trial, including 29 subjects with screen-detected LC (17 prevalent and 12 incident) and 108 subjects with benign nodules. The predictive capability of baseline cfDNA to differentiate malignant and benign nodules was compared to that of Lung-RADS classification and Brock score at initial LDCT (iLDCT). Subjects with prevalent LC showed both well-discriminating radiological characteristics of the malignant nodule (16 of 17 were classified as Lung-RADS 4) and markedly increased cfDNA (mean 18.8 ng/mL). The mean diameters and Brock scores of malignant nodules at iLDCT in subjects who were diagnosed with incident LC were not different from those of benign nodules. However, 75% (9/12) of subjects with incident LC showed a baseline cfDNA ≥ 3.15 ng/mL, compared to 34% (37/108) of subjects with benign nodules (p = 0.006). Moreover, baseline cfDNA was correlated (p = 0.001) with tumor growth, measured with volume doubling time. In conclusion, increased baseline cfDNA may help to differentiate subjects with malignant and benign nodules at LDCT. [ABSTRACT FROM AUTHOR]

Simple Summary: In the present study, the intraoperative fluorescence of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) is investigated in 80 cases. Brain metastases fluoresced in 57.5% of cases, with no significant correlation between fluorescence and primary tumor or histological subtype. Complete resection of brain metastases was detected in 82.5%, of which 56.1% were fluorescence positive, compared to 43.9% which were non-fluorescent. Thus, prior administration of 5-ALA tended to improve the resectability rate by 12.1%. Fluorescence-positive and -negative metastases showed significantly different overall survival in this study. Therefore, administration of 5-ALA as a surgical adjuvant may be beneficial in resecting brain metastases and may potentially optimize the surgical procedure. (1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The aim was to investigate whether the resection of brain metastases using 5-ALA fluorescence also leads to a more complete resections and thus to a prolongation of survival; (2) Methods: The following variables have been considered: age, sex, number of metastases, localization, involvement of eloquent area, correlation between fluorescence and primary tumor/subtype, resection, and survival time. The influence on the degree of resection was determined with a control MRI within the first three postoperative days; (3) Results: Brain metastases fluoresced in 57.5% of cases. The highest fluorescence rates of 73.3% were found in breast carcinoma metastases and the histologic subtype adenocarcinoma (68.1%). No correlation between fluorescence behavior and localization, primary tumor, or histological subtype was found. Complete resection was detected in 82.5%, of which 56.1% were fluorescence positive. There was a trend towards improved resectability (increase of 12.1%) and a significantly longer survival time (p = 0.009) in the fluorescence-positive group; (4) Conclusions: 5-ALA-assisted extirpation leads to a more complete resection and longer survival and can therefore represent a low-risk addition to modern surgery for brain metastases. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective study focused on 23 patients diagnosed with Hepatocellular Carcinoma (HCC), utilizing the Liver Imaging Reporting and Data System (LI-RADS) for classification. This system aids in the non-invasive diagnosis of HCC, potentially eliminating the need for a diagnostic biopsy. Patients were selected based on their diagnosis, confirmed either via imaging methods that identified advanced liver nodules or via histopathological findings consistent with HCC, including specific protein markers. The study aimed to assess the histopathological changes resulting from prior local interventions, such as trans-arterial chemoembolization or radiofrequency ablation, and their impact on the tumor's response to subsequent immune therapies. Key findings indicated variations in alpha-fetoprotein levels and increased expression of the immune marker PD-L1 in untreated patients, suggesting a more aggressive cancer progression in these individuals. The study's conclusions support the use of liver biopsy in refining therapeutic approaches for HCC, particularly in recurrent cases post-intervention, to enhance personalized immune therapy strategies. Background: The Liver Imaging Reporting and Data System (LI-RADS) combines standardized terminology with a classification system for imaging findings in patients with HCC, therefore rendering diagnostic biopsy unnecessary in many cases. This retrospective study included 23 patients with a biopsy diagnosis of HCC, performed either before or after local interventional procedures, in order to evaluate the histopathologic changes induced by previous procedures and their potential influence on the response to immune therapy. Material and Methods: The study encompassed a cohort of patients diagnosed with Hepatocellular Carcinoma (HCC). Diagnosis was established via contrast-enhanced computer tomography or magnetic resonance imaging that identified LI-RADS-5 nodules in conjunction with historical liver disease and elevated alpha-fetoprotein (AFP) levels or via histological examination confirming positivity for glypican3, heat shock protein 70, and glutamine synthetase. The study detailed the liver disease etiology, LI-RADS scores, characteristics and dimensions of HCC nodules, serum AFP concentrations, Edmondson–Steiner grading, and the expression of programmed cell death ligand 1 (PD-L1) in the tumor cells. Results: Among the study's cohort of Hepatocellular Carcinoma (HCC) patients, a portion had not received any prior treatments, while the remainder experienced local HCC recurrence following trans-arterial chemoembolization or radiofrequency ablation. Observations indicated elevated alpha-fetoprotein (AFP) levels in those who had not undergone any previous interventions, showing statistical significance. The Edmondson–Steiner classification predominantly identified grade III differentiation across patients, irrespective of their treatment history. Furthermore, an increase in intra-tumoral programmed cell death ligand 1 (PD-L1) expression was noted in patients who had not been subjected to previous therapies. Conclusion: Liver biopsy offers valuable insights for patients with Hepatocellular Carcinoma (HCC), assisting in the tailoring of immune therapy strategies, particularly in cases of recurrence following prior local interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: The exact cellular origin of glioblastoma (GBM) remains uncertain, with prevalent theories suggesting emergence from transformed endogenous stem cells. These cells likely play pivotal roles in tumor initiation and progression. The impact of proximity of GBM to the brain's neurogenic zones on patient survival remains a lingering question. Our study investigated tumor infiltration into the subventricular zone (SVZ), the subgranular zone (SGZ) and the cortex alongside clinical variables, such as KPS score, multifocality and selected molecular markers. Utilizing a fully automated processing and segmentation pipeline, we objectively quantified these relationships in 177 IDH wild-type glioblastomas. Our findings support prior research indicating SVZ proximity as a predictor for poor survival, while SGZ proximity showed no significant impact. We also established new survival thresholds based on tumor mass fractions and minimal distances. Contrary to previous studies, we found no significant correlations between SVZ contact and multifocal growth pattern or MGMT promoter methylation. So far, the cellular origin of glioblastoma (GBM) needs to be determined, with prevalent theories suggesting emergence from transformed endogenous stem cells. Adult neurogenesis primarily occurs in two brain regions: the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus. Whether the proximity of GBM to these neurogenic niches affects patient outcome remains uncertain. Previous studies often rely on subjective assessments, limiting the reliability of those results. In this study, we assessed the impact of GBM's relationship with the cortex, SVZ and SGZ on clinical variables using fully automated segmentation methods. In 177 glioblastoma patients, we calculated optimal cutpoints of minimal distances to the SVZ and SGZ to distinguish poor from favorable survival. The impact of tumor contact with neurogenic zones on clinical parameters, such as overall survival, multifocality, MGMT promotor methylation, Ki-67 and KPS score was also examined by multivariable regression analysis, chi-square test and Mann–Whitney-U. The analysis confirmed shorter survival in tumors contacting the SVZ with an optimal cutpoint of 14 mm distance to the SVZ, separating poor from more favorable survival. In contrast, tumor contact with the SGZ did not negatively affect survival. We did not find significant correlations with multifocality or MGMT promotor methylation in tumors contacting the SVZ, as previous studies discussed. These findings suggest that the spatial relationship between GBM and neurogenic niches needs to be assessed differently. Objective measurements disprove prior assumptions, warranting further research on this topic. [ABSTRACT FROM AUTHOR]

Simple Summary: We aimed to identify risk factors and evaluate the accuracy of existing risk stratifications developed for non-muscle-invasive bladder cancer (NMIBC) regarding their ability to predict high-grade recurrence and progression. We included 171 NMIBC patients treated with TURBT and adjuvant BCG, of whom 73 experienced recurrence (42.7%), and 29 developed progression (17%). Available risk models (EORTC/ CUETO/ EAU) demonstrated limited accuracy in predicting high-grade recurrence-free (RFS) and progression-free survival (PFS). Multivariable analysis identified independent predictors for high-grade RFS, including T1HG tumor at repeat TURBT, tumor multiplicity, previous history of high-grade NMIBC, and EORTC2006 progression risk score. In conclusion, the available risk models lack accuracy in predicting high-grade RFS and PFS in BCG-treated NMIBC, suggesting potential improvement with the inclusion of additional risk factors. The currently available EORTC, CUETO and EAU2021 risk stratifications were originally developed to predict recurrence and progression in non-muscle-invasive bladder cancer (NMIBC). However, they have not been validated to differentiate between high-grade (HG) and low-grade (LG) recurrence-free survival (RFS), which are distinct events with specific implications. We aimed to evaluate the accuracy of available risk models and identify additional risk factors for HG RFS and PFS among NMIBC patients treated with Bacillus Calmette–Guérin (BCG). We retrospectively included 171 patients who underwent transurethral resection of the bladder tumor (TURBT), of whom 73 patients (42.7%) experienced recurrence and 29 (17%) developed progression. Initially, there were 21 low-grade and 52 high-grade recurrences. EORTC2006, EORTC2016 and CUETO recurrence scoring systems lacked accuracy in the prediction of HG RFS (C-index 0.63/0.55/0.59, respectively). EAU2021 risk stratification, EORTC2006, EORTC2016, and CUETO progression scoring systems demonstrated low to moderate accuracy (C-index 0.59/0.68/0.65/0.65) in the prediction of PFS. In the multivariable analysis, T1HG at repeat TURBT (HR = 3.17 p < 0.01), tumor multiplicity (HR = 2.07 p < 0.05), previous history of HG NMIBC (HR = 2.37 p = 0.06) and EORTC2006 progression risk score (HR = 1.1 p < 0.01) were independent predictors for HG RFS. To conclude, available risk models lack accuracy in predicting HG RFS and PFS in -NMIBC patients treated with BCG. [ABSTRACT FROM AUTHOR]

Simple Summary: Osteosarcoma is one of the most lethal bone tumors worldwide. Immune checkpoint blockades have achieved significant success in solid tumors; however, their role in osteosarcoma remains obscure. Therefore, we aim to explore the clinical significance of soluble immune checkpoint-related proteins in osteosarcoma in this study. We identified four soluble immune checkpoint-related proteins as predictors of progress-free survival and lung metastasis-free survival of osteosarcoma patients. Our findings indicated that soluble immune checkpoint-related proteins could be promising biomarkers for the outcomes and immunotherapy of osteosarcoma. Background: The immune checkpoint blockade remains obscure in osteosarcoma (OS). We aim to explore the clinical significance of soluble immune checkpoint (ICK)-related proteins in OS. Methods: We profiled 14 soluble ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, CD28, CD80, CD137, CD27, and CTLA-4) in the plasma of 76 OS patients and matched controls. We evaluated the associations between the biomarkers and the risk of OS using unconditional multivariate logistic regression. The multivariate Cox model was utilized to develop the prediction model of OS. Immune subtypes were established from the identified biomarkers. Transcriptional data from GEO were analyzed to elucidate potential mechanisms. Results: We found that sTIM3, sCD137, sIDO, and sCTLA4 were significantly correlated with OS risk (all p < 0.05). sBTLA, sPDL2, and sCD27 were significantly associated with the risk of lung metastasis, whereas sBTLA and sTIM3 were associated with the risk of disease progression. We also established an immune subtype based on sBTLA, sPD1, sTIM3, and sPDL2. Patients in the sICK-type2 subtype had significantly decreased progression-free survival (PFS) and lung metastasis-free survival (LMFS) than those in the sICK-type1 subtype (log-rank p = 2.8 × 10−2, 1.7 × 10−2, respectively). Interestingly, we found that the trend of LMFS and PFS in the subtypes of corresponding ICK genes' expression was opposite to the results in the blood (log-rank p = 2.6 × 10−4, 9.5 × 10−4, respectively). Conclusion: Four soluble ICK-related proteins were associated with the survival of OS patients. Soluble ICK-related proteins could be promising biomarkers for the outcomes and immunotherapy of OS patients, though more research is warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Allogeneic stem cell transplantation (allo-SCT) represents the only potentially curative treatment for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), but up to 50% of patients relapse after allo-SCT. The salvage therapy after disease recurrence is not standardized, and the outcome remains unfavorable. Therefore, there is a growing interest in determining the most effective approach to manage the post-transplant phase with the goal of promptly detecting disease recurrence or preventing it. In this context, we conducted a retrospective study to assess the overall survival (OS) of patients with relapsed AML or MDS after allo-SCT with the aim of acquiring useful information for identifying the best prospective therapeutic strategy. The OS was evaluated according to the type of therapy, whether it included donor lymphocyte infusion (DLI), the timing of administration, and whether it occurred during an overt hematological relapse or in a preemptive setting. Background: Disease relapse after allogeneic stem cell transplantation (allo-SCT) is the main challenge for curing acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We investigated the overall survival (OS) after allo-SCT relapse according to different therapeutic approaches. Methods: We analyzed 134 patients who relapsed after allo-SCT performed between 2015 and 2021 at Saint-Antoine University Hospital, Paris and Spedali Civili di Brescia, Brescia. Of these, 103 (77%) were treated, comprising 69/103 (67%) who received therapy in overt relapse and 34/103 (33%) who were treated in a pre-emptive manner when molecular/cytogenetics recurrence or mixed chimerism occurred. The treatment was donor lymphocyte infusion (DLI)-based for 40/103 (39%) patients. Results: The 1-, 2-, and 5-year OS of patients treated with DLI (n = 40) was 67%, 34%, and 34%, respectively, for those treated preventively (n = 20) and 43%, 20%, and 20%, respectively, for those treated in overt relapse (n = 20) (p < 0.01). The 1-, 2-, and 5-year OS of patients treated without DLI (n = 63) was 54%, 40%, and 26%, respectively, for those treated preventively (n = 14) and 17%, 5%, and 0%, respectively, for those treated in overt relapse (n = 49) (p < 0.01). Conclusions: Relapse treatment with a pre-emptive strategy was associated with improved outcomes, particularly when DLI was employed. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of robot-assisted radical cystectomy (RARC) is increasing, although its definitive superiority over open radical cystectomy (ORC) has not been proven. Randomized controlled trials (RCTs) have demonstrated RARC's superiority regarding perioperative and functional outcomes but not in terms of oncologic and survival outcomes. Composite outcomes, such as the trifecta and pentafecta, have been proposed to evaluate the quality of the surgery. The aim of our retrospective study was to assess the superiority of RARC over ORC using the PROMETRIC group's trifecta and pentafecta criteria in a propensity score-matched analysis to reduce biases. No differences were found in the success rates of trifecta and pentafecta. The overall survival was comparable between the two cohorts. We confirmed the superiority of RARC in significantly reducing the estimated blood loss and perioperative transfusion rates. Background: This study aimed to evaluate the surgical and oncological outcomes of robot-assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) using trifecta and pentafecta parameters. Methods: The clinical data of 41 patients who underwent RARC between 2018 and 2022 were prospectively collected and retrospectively compared to those of 330 patients undergoing ORC using 1:1 propensity score matching. Trifecta was defined as simultaneous negative surgical margins (SMs), a lymph node (LN) yield ≥ 16, and the absence of major complications (Clavien–Dindo grade III–V) within 90 days postoperatively. Pentafecta additionally included a 12-month recurrence-free rate and a time between the transurethral resection of a bladder tumor (TURBT) and radical cystectomy (RC) ≤ 3 months. The continuous variables were compared using the Mann–Whitney U test, and the categorical variables were analyzed using the chi-squared test. Results: No statistically significant differences in trifecta and pentafecta success rates were observed between the RARC and ORC cohorts after propensity score matching. However, the RARC group exhibited significantly reduced blood loss (RARC: 317 mL vs. ORC: 525 mL, p = 0.01). Conclusions: RARC offers distinct advantages over ORC in terms of reduced blood loss, while trifecta and pentafecta success rates do not differ significantly between the two surgical approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: Two Israeli studies about medical marijuana potentially interfering with immunotherapies like nivolumab for cancer treatment have received substantial attention. However, there have been anonymous but detailed concerns about these reports on PubPeer. This team attempted to verify the data analysis and statistics of these two reports and the published correction. Many findings, including some that could impact the statistical conclusions, could not be verified. Of 22 statistical in the prospective report, 4 could not be repeated using the same statistics or with the provided N. The p-value on 17 corresponded with that of a different statistical test than was listed in the methods. Re-analysis also identified some previously unreported significant differences (e.g., age) between cannabis users and non-users at baseline. Further study of the safety of immunotherapy and cannabis combination may be warranted using patient groups that have been matched on key demographic and medical variables. A retrospective (N = 140) and a prospective (N = 102) observational Israeli study by Bar-Sela and colleagues about cannabis potentially adversely impacting the response to immunotherapy have together been cited 202 times, including by clinical practice guidelines. There have also been concerns on PubPeer outlining irregularities and unverifiable information in their statistics and numerous errors in calculating percentages. This reanalysis attempted to verify the data analysis while including non-parametric statistics. The corrected prospective report contained 22 p-values, but only one (4.5%) could be verified despite the authors being transparent about the N and statistics employed. Cannabis users were significantly (p < 0.0025) younger than non-users, but this was not reported in the retrospective report. There were also errors in percentage calculations (e.g., 13/34 reported as 22.0% instead of 38.2%). Overall, these observational investigations, and especially the prospective, appear to contain gross inaccuracies which could impact the statistical decisions (i.e., significant findings reported as non-significant or vice-versa). Although it is mechanistically plausible that cannabis could have immunosuppressive effects which inhibit the response to immunotherapy, these two reports should be viewed cautiously. Larger prospective studies of this purported drug interaction that account for potential confounds (e.g., greater nicotine smoking among cannabis users) may be warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: For effective cancer treatment, it is important to scrutinize individual driver gene mutations. In this study, we investigated whether analyzing gene mutations in primary breast cancer based on ctDNA could be a biomarker of prognosis using plasma from 95 patients with primary breast cancer. The key finding was that TP53 and/or BRCA1 mutation-positive groups had poor recurrence-free survival in the TNBC patients compared to TP53 and BRCA1 mutation-negative groups. This result indicates that TP53 and/or BRCA1 mutations on ctDNA could be useful prognostic markers in TNBC patients. Precise biomarkers for predicting the therapeutic efficacy of molecularly targeted drugs are limited at the protein level; thus, it has been important to broadly scrutinize individual cancer driver gene mutations for effective cancer treatments. Multiplex cancer genome profiling can comprehensively identify gene mutations that are therapeutic targets using next-generation sequencing (NGS). In addition, circulating tumor DNA (ctDNA) is a DNA fragment released into the blood by tumor cell-derived cell death or apoptosis. Liquid biopsy with ctDNA is a novel clinical test for identifying genetic mutations in an entire population noninvasively, in real-time, and heterogeneously. Although there are several reports on ctDNA, fewer have evaluated ctDNA with NGS before an initial treatment for breast cancer patients. Therefore, we examined whether analyzing tumor-associated gene mutations in primary breast cancer based on ctDNA could serve as a biomarker for prognosis and optimal treatment selection. Ninety-five primary breast cancer patients treated at our department from January 2017 to October 2020 were included. Pretreatment plasma samples were subjected to NGS analysis of ctDNA, and correlations with patients' clinicopathological characteristics were evaluated. Fifty-nine (62.1%) patients were positive for ctDNA. ctDNA tended to be positive in hormone receptor-negative, and TP53 (34%), BRCA1 (20%), and BRCA2 (17%) gene mutations were more frequent. Regarding recurrence-free survival, the prognosis was poor in the TP53 and/or BRCA1 mutation-positive groups, especially in triple-negative breast cancer (TNBC) patients. In conclusion, the results of this study indicate that ctDNA with liquid biopsy could identify the poor prognosis group before treatment among TNBC patients and for those for whom optimal treatment selection is desirable; additionally, optimal treatment could be selected according to the ctDNA analysis results. [ABSTRACT FROM AUTHOR]

Simple Summary: The location of the primary tumor in the right colon, left colon, or rectum affects the efficacy of biological drugs used in the treatment of metastatic colorectal cancer, but how? We examined how the primary tumor location affects disease characteristics, treatability, quality of life, and outcome in a real-life study population of 1080 Finnish patients in the RAXO study. The primary tumor location correlates with the location of metastases, the frequency of gene mutations, how often metastases can be operated upon, long-term survival after curative surgery or palliative chemotherapy, and the quality of life during the disease trajectory. The primary tumor location is a helpful surrogate for clinicians working with metastatic colorectal cancer patients in estimating the clinical course of the disease. This study cannot identify the reasons for the associations, i.e., whether it is the primary location per se, the different mutations, or other reasons. The primary tumor location (PTL) is associated with the phenotype, metastatic sites, mutations, and outcomes of metastatic colorectal cancer (mCRC) patients, but this has mostly been studied according to sidedness (right vs. left sided). We studied right colon vs. left colon vs. rectal PTL in a real-life study population (n = 1080). Health-related quality of life (HRQoL) was assessed multi-cross-sectionally with QLQ-C30, QLQ-CR29, EQ-5D, and 15D. A chi-square, Kaplan–Meier, and Cox regression were used to compare the groups. The PTL was in the right colon in 310 patients (29%), the left colon in 396 patients (37%), and the rectum in 375 patients (35%). The PTL was associated with distinct differences in metastatic sites during the disease trajectory. The resectability, conversion, and resection rates were lowest in the right colon, followed by the rectum, and were highest in the left colon. Overall survival was shortest for right colon compared with left colon or rectal PTL (median 21 vs. 35 vs. 36 months), with the same trends after metastasectomy or systemic therapy only. PTL also remained statistically significant in a multivariable model. The distribution of symptoms varied according to PTL, especially between the right colon (with general symptoms of metastases) and rectal PTL (with sexual- and bowel-related symptoms). mCRC, according to PTL, behaves differently regarding metastatic sites, resectability of the metastases, outcomes of treatment, and HRQoL. [ABSTRACT FROM AUTHOR]

Simple Summary: The recent increase in oropharyngeal cancer cases in Western countries prompted this research, which focuses on evaluating the role of human papillomavirus (HPV) in the incidence of this cancer type in Romania. This study employed p16 overexpression as a biomarker to distinguish HPV-related oropharyngeal cancers from those attributed to other etiologies, like smoking and alcohol consumption. Comparative analysis of treatment responses revealed a markedly improved prognosis in patients with p16-positive oropharyngeal cancers, underscoring the significance of HPV in the pathogenesis and clinical outcomes of these malignancies. Background: Oropharyngeal cancer is a global health concern due to its multifaceted nature. Recent molecular studies have linked p16 overexpression, associated with the human papillomavirus, to oropharyngeal cancer and its prognostic implications. Materials and Methods: This retrospective study in Western Romania examined 60 patients, categorizing them based on p16 biomarker status: 28 were p16 positive, and 32 were p16 negative. Statistical tests, including Fisher's exact and chi2, were used for analysis. Results: Patients with p16-positive oropharyngeal cancer exhibited a better prognosis (3-year survival, p = 0.0477; midtreatment, p = 0.0349) and reported lower alcohol (p = 0.0046) and tobacco (p < 0.0001) use. Conclusions: The study highlights the importance of p16 testing in oropharyngeal carcinoma diagnosis. It suggests modifying treatment approaches based on p16 status and underscores the differing prognoses associated with p16-positive and p16-negative cases. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study was to evaluate the incidence of high-grade glandular pathology in the histological cones of LEEP for CIN3 and to verify the different biological nature of the single CIN3 lesion from CIN3 coexisting with AIS. A sample of 414 women underwent LEEP for CIN3. From the histological examination of the cone, we selected 370 women with a single CIN3, 39 women with CIN3 coexisting with AIS, and 5 women with CIN3 coexisting with AC. Specific HR HPV genotypes and treatment outcome in the study groups were investigated. Women with CIN3 coexisting with AIS showed only four specific HR HPV genotypes (16, 18, 45, 33), the prevalence of genotype 18, the presence of skip lesions (9%), and occult adenocarcinoma (one case of 1A1 adenocarcinoma). Furthermore, CIN3 lesions coexisting with AIS have a higher rate of viral persistence and recurrence than single CIN3 lesions. These characteristics make CIN3 coexisting with AIS closer to the glandular pathology than to the squamous one, making hysterectomy necessary and cervical conization insufficient, which is instead considered the optimal treatment method for a single CIN3. The purpose of this study was to evaluate the incidence of AIS and AC in the histological cone of women treated for CIN3. Furthermore, through the study of the specific HR HPV genotypes, we obtained more information on the possible different nature between the single CIN3 lesion and the CIN3 coexisting with the glandular lesion. Methods. A sample of 414 women underwent LEEP for CIN3. The study sample consisted of 370 women with a CIN3 lesion alone and 44 women with a CIN3 lesion coexisting with AIS or adenocarcinoma. We studied the individual HR HPV genotypes and their frequency in the two groups under study. Furthermore, the therapeutic results and follow-ups for the population were studied on the entire study sample. Results. In patients with a single CIN3 lesion, 11 high-risk genotypes were detected; in patients with CIN3 associated with AIS or AC, only 4 different genotypes were detected (16, 18, 45, 33). Overall, the frequency of HPV 18 was significantly higher in CIN3 coexisting with AIS compared to solitary CIN3 lesions, χ2 = 27.73 (p < 0.001), while the frequency of other high-risk genotypes was significantly higher in patients with a single CIN3 than in patients with CIN3 coexisting with AIS. In our study population, mixed lesions (CIN3 coexisting with AIS), unlike their squamous counterparts (single CIN3 lesions), were characterized by skip lesions, which demonstrate more aggressive behavior and a higher rate of viral persistence and recurrence. Conclusion. A relatively high rate (10.7%) of AIS-AC was found in women treated for CIN3. Our study confirms the multifocal biological nature of the CIN3 lesion coexisting with AIS compared to the single CIN3 lesion. All this justifies the different treatments to which CIN3 lesions coexisting with AIS are addressed; in fact, the latter are treated with hysterectomy, while CIN3 is treated with conization alone. [ABSTRACT FROM AUTHOR]

Simple Summary: Initial management approaches for prevascular mediastinal tumors (PMTs) can be divided into two categories: direct surgery and core needle biopsy (CNB). Although the gold standard diagnostic method is histopathological examination, the selection of the initial management between direct surgery and CNB is more urgent for patients with PMTs, compared with the definite diagnosis of PMT subtypes. The study aimed to develop clinical–radiomics machine learning (ML) classification models to differentiate patients who needed direct surgery from patients who needed CNB, among the patients with PMTs. An ensemble learning model, combining five ML models, had a classification accuracy of 90.4% (95% CI = 87.9 to 93.0%), which significantly outperformed clinical diagnosis (86.1%; p < 0.05), which may be used as clinical decision support system to facilitate the selection of the initial management of PMT. The study aimed to develop machine learning (ML) classification models for differentiating patients who needed direct surgery from patients who needed core needle biopsy among patients with prevascular mediastinal tumor (PMT). Patients with PMT who received a contrast-enhanced computed tomography (CECT) scan and initial management for PMT between January 2010 and December 2020 were included in this retrospective study. Fourteen ML algorithms were used to construct candidate classification models via the voting ensemble approach, based on preoperative clinical data and radiomic features extracted from the CECT. The classification accuracy of clinical diagnosis was 86.1%. The first ensemble learning model was built by randomly choosing seven ML models from a set of fourteen ML models and had a classification accuracy of 88.0% (95% CI = 85.8 to 90.3%). The second ensemble learning model was the combination of five ML models, including NeuralNetFastAI, NeuralNetTorch, RandomForest with Entropy, RandomForest with Gini, and XGBoost, and had a classification accuracy of 90.4% (95% CI = 87.9 to 93.0%), which significantly outperformed clinical diagnosis (p < 0.05). Due to the superior performance, the voting ensemble learning clinical–radiomic classification model may be used as a clinical decision support system to facilitate the selection of the initial management of PMT. [ABSTRACT FROM AUTHOR]

Simple Summary: In the literature, between 30% and 80% of all patients with cancer are reported to be malnourished or cachectic. Our objectives included identifying the risk factors for malnutrition in patients with ovarian cancer, determining the diagnostic relevance of the commonest methods used to assess nutritional status in these patients, and evaluating the predictive and prognostic values of malnutrition in patients with primary and relapsed ovarian cancer. We found malnutrition as an independent predictor of incomplete cytoreduction and an independent prognostic factor for poor overall survival. Preoperative nutritional assessment is an effective tool in the identification of high-risk groups of ovarian cancer characterized by poor clinical outcome. Background: Malnutrition was associated with worse survival outcomes, impaired quality of life, and deteriorated performance status across various cancer types. We aimed to identify risk factors for malnutrition in patients with epithelial ovarian cancer (EOC) and impact on survival. Methods: In our prospective observational monocentric study, we included the patients with primary and recurrent EOC, tubal or peritoneal cancer conducted. We assessed serum laboratory parameters, body mass index, nutritional risk index, nutritional risk screening score (NRS-2002), and bio-electrical impedance analysis. Results: We recruited a total of 152 patients. Patients > 65 years-old, with ascites of >500 mL, or with platinum-resistant EOC showed statistically significant increased risk of malnutrition when evaluated using NRS-2002 (p-values= 0.014, 0.001, and 0.007, respectively). NRS-2002 < 3 was an independent predictive factor for complete tumor resectability (p = 0.009). The patients with NRS-2002 ≥ 3 had a median overall survival (OS) of seven months (95% CI = 0–24 months), as compared to the patients with NRS-2002 < 3, where median OS was forty-six months (p = 0.001). A phase angle (PhAα) ≤ 4.5 was the strongest predictor of OS. Conclusions: In our study, we found malnutrition to be an independent predictor of incomplete cytoreduction and independent prognostic factor for poor OS. Preoperative nutritional assessment is an effective tool in the identification of high-risk EOC groups characterized by poor clinical outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: Individual differences exist in the tolerability of surgical intervention among elderly patients, and it is necessary for appropriate treatment planning. The aim of our retrospective study was to investigate the efficacy of markers of preoperative inflammatory and nutritional status and identified perioperative high-risk elderly patients with gastric cancer. We analyzed whether preoperative inflammatory nutritional markers of 571 gastric cancer patients (<65 years old; n = 192, ≥65 years old; n = 379) can predict postoperative short-term and long-term outcomes. Preoperative high C-reactive albumin ratio (CAR) was not only associated with the occurrence of postoperative complications but also with poor prognosis in elderly gastric cancer patients. However, these trends were not observed among younger patients. The importance of these findings is that CAR has the potential to be used as a simple tool to predict short- and long-term postoperative outcomes that reflect the nutritional inflammatory status of the elde. Individualized preoperative assessment of the general condition of elderly patients with gastric cancer is necessary for appropriate surgical treatment planning. This study investigated the efficacy of preoperative markers that could be easily calculated from preoperative peripheral blood to predict the short- and long-term postoperative outcomes of gastrectomy. In total, 571 patients who underwent R0 surgical resection for gastric cancer were enrolled. In the elderly patient group (≥65 years old), univariate analyses revealed that the incidence of postoperative complications was associated with poor performance status (p = 0.012), more comorbidities (p = 0.020), high C-reactive protein to albumin ratio (CAR, p = 0.003), total gastrectomy (p = 0.003), open approach (p = 0.034), blood transfusion (p = 0.002), and advanced cancer (p = 0.003). Multivariate analysis showed that a high CAR was associated with a high incidence of postoperative complications (p = 0.046). High CAR was also associated with poor OS (p = 0.015) and RFS (p = 0.035). However, these trends were not observed among younger patients (<65 years old). Preoperative CAR may play a significant role in predicting short- and long-term surgical outcomes, particularly in elderly patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: The evaluation of additional body composition measures, such as visceral adipose tissue area, subcutaneous adipose tissue area, and sarcopenic obesity, could be useful to improve our understanding of the prognostic role of body composition parameters in women with breast cancer. The aim of our review was to summarize current evidence about sarcopenia in non-metastatic as well as metastatic breast cancer (MBC) and to identify any correlation between sarcopenia and patient outcomes. We observed a correlation between sarcopenia and significantly higher rates of treatment-related toxicities in both settings (metastatic and non-metastatic) compared with patients without sarcopenia. It was found that sarcopenic patients were more likely to deal with severe toxicities compared to patients classified as non-sarcopenic. This finding suggests that sarcopenia recently emerged as a new condition that, independently from malnutrition, may adversely affect patient outcomes and may be used as a reference for chemotherapy dose selection to better balance individual pharmacokinetic differences. (1) Background: We estimated the prevalence and clinical outcomes of sarcopenia among breast cancer patients. (2) Methods: A systematic literature search was carried out for the period between July 2023 and October 2023. Studies with breast cancer patients evaluated for sarcopenia in relation to overall survival (OS), progression-free survival (PFS), relapse of disease (DFS), pathological complete response (pCR), or toxicity to chemotherapy were included. (3) Results: Out of 359 screened studies, 16 were eligible for meta-analysis, including 6130 patients, of whom 5284 with non-MBC. Sarcopenia was evaluated with the computed tomography (CT) scan skeletal muscle index and, in two studies, with the dual-energy x-ray absorptiometry (DEXA) appendicular lean mass index. Using different classifications and cut-off points, overall, there were 2007 sarcopenic patients (33%), of whom 1901 (95%) presented with non-MBC. Sarcopenia was associated with a 33% and 29% higher risk of mortality and progression/relapse of disease, respectively. Sarcopenic patients were more likely to develop grade 3–4 toxicity (OR 3.58, 95% CI 2.11–6.06, p < 0.0001). In the neoadjuvant setting, a higher rate of pCR was observed among sarcopenic patients (49%) (OR 2.74, 95% CI 0.92–8.22). (4) Conclusions: Our meta-analysis confirms the correlation between sarcopenia and negative outcomes, especially in terms of higher toxicity. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explored the predictive value of neutrophils and neutrophil-related biomarkers as auxiliary diagnosis biomarkers of NSCLC in an ongoing large cohort. IL-6 and IL-1RA were identified as independent risk factors for NSCLC. These findings can improve the predictive performance beyond epidemiological variables and classic neutrophil-related biomarkers in identifying NSCLC. Background: Recent studies have revealed that neutrophils play a crucial role in cancer progression. This study aimed to explore the diagnostic value of neutrophil-related biomarkers for non-small-cell lung cancer (NSCLC). Methods: We initially assessed the associations between classic neutrophil-related biomarkers (neutrophil-to-lymphocyte ratio (NLR), absolute neutrophil counts (NEU), absolute lymphocyte counts (LYM)) and NSCLC in 3942 cases and 6791 controls. Then, we measured 11 novel neutrophil-related biomarkers via Luminex Assays in 132 cases and 66 controls, individually matching on sex and age (±5 years), and evaluated their associations with NSCLC risk. We also developed the predictive models by sequentially adding variables of interest and assessed model improvement. Results: Interleukin-6 (IL-6) (odds ratio (OR) = 10.687, 95% confidence interval (CI): 3.875, 29.473) and Interleukin 1 Receptor Antagonist (IL-1RA) (OR = 8.113, 95% CI: 3.182, 20.689) shows strong associations with NSCLC risk after adjusting for body mass index, smoking status, NLR, and carcinoembryonic antigen. Adding the two identified biomarkers to the predictive model significantly elevated the model performance from an area under the receiver operating characteristic curve of 0.716 to 0.851 with a net reclassification improvement of 97.73%. Conclusions: IL-6 and IL-1RA were recognized as independent risk factors for NSCLC, improving the predictive performance of the model in identifying disease. [ABSTRACT FROM AUTHOR]

Simple Summary: The accessory parotid gland differs in histological structure from main parotid tissue, making the appearance of tumours different than those in the rest of the gland. Therefore, our aim was to analyse the epidemiological and histological differences of parotid tumours located in regions I–V, with particular emphasis on the distinctiveness of region V. Furthermore, to define the epidemiological factors that will indicate the risk of histological malignancy from clinically benign appearances was our object of interest. We confirmed our hypothesis that the epidemiology, clinical behaviour, histology, tactics of the surgical procedure, route of access, and prognosis differ in the parotid gland tumours located in superficial (region I, II) and deep (region III, IV) lobes, as well as the accessory lobe (region V), despite originating from the one organ. The accessory parotid gland (APG, Vth level) differs in histological structure from main parotid tissue. This gives rise to the hypothesis, mirrored in clinical observations, that the representation of tumours is different than in the rest of the gland. The aim of the study was to analyse the epidemiological and histological differences of parotid tumours located in regions I–V, with particular emphasis on the distinctiveness of region V. To define the epidemiological factors that will indicate the risk of histological malignancy from clinically benign appearance, multicentre prospective studies conducted between 2017–2021 by five Head and Neck Surgery University Departments, cooperating within the Polish Salivary Network Database 1929 patients (1048 women and 881 men), were included. The age, gender, patient occupation, place of inhabitation, tumour size, clinical features of malignancy, histology, and facial nerve (FN) paresis were analysed for superficial (I_II) and deep (III_IV) lobes and with special regard to the tumours affecting region V. Twenty eight tumours were located exclusively in region V (1.45% total) and seventy-two tumours were found in region V exhibiting extensions to neighbouring regions (3.7% total), characterised as significantly younger and less frequent in retirees. In I–IV regions, approximately 90% of tumours were benign, with pleomorphic adenoma (PA) and Whartin tumour (WT) predominance. In region V, PA exceeded 75% but WT were casuistic (2/28). Incidences of malignancies in region V was 40% but clinical signs of malignancy were evident only in tumours > 4 cm or in the presence of FN paresis. In 19% of patients with a benign appearance, imaging revealed malignancy; however, 38% of patients showed false negative results both in terms of clinical and radiological features of malignancy. Logistic regression models in 28 patients with tumours located exclusively in region V vs. 1901 other patients and in 100 patients with V extension vs. 1829 other patients showed no clinical symptoms of malignancy binding with final malignant tumour histology as a single variable or in combination with other variables. The logistic regression models obtained in this study show strong linkage between tumour location and predictors (age, male gender, and tumour diameter) and also aimed to function as a good classifier. Our conclusion is that, despite the very clear image of the mid-cheek tumour which is easily accessible in palpation and ultrasound examination, it is necessary to improve oncological vigilance and preoperative patient preparation. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral endocrine therapy is a key component of breast cancer treatment in hormone-positive patients, the most frequent subtype of this cancer. Adherence to this treatment is a factor related to an increased probability of relapse and death. The COVID-19 pandemic has had a disruptive impact on the use of cancer services, delaying diagnosis and stopping screening during the peak of the pandemic. We assessed the impact of the COVID-19 on the adherence to oral endocrine therapy in Catalonia (Spain) using the data collected in the clinical records of the public health care system. We have found that the first wave of the COVID-19 (between March and September 2020) was associated with a modest impact on treatment adherence. Purpose. To assess the impact of the COVID-19 pandemic on adherence to oral endocrine therapy in patients diagnosed with breast cancer in the public healthcare system in Catalonia (Spain). Methods. Retrospective cohort study in patients starting endocrine therapy from 2017 to 2021. Adherence was measured during the first year of treatment, and the impact of the pandemic was calculated according to the calendar year and whether the first year of treatment included the peak period of the pandemic in our setting (March–September 2020). Analyses were performed using a chi-square test and multivariable logistic regression, with results stratified by year, age group, and drug type. Results. Mean overall adherence during the first year of treatment was 89.6% from 2017 to 2021. In contrast, the patients who started treatment in 2019 and 2020 and whose treatment included the peak pandemic period presented an adherence of 87.0% and 86.5%, respectively. Young age and tamoxifen or combination therapy were predictors of low adherence. An increase in neoadjuvant therapy was also observed in 2020. Conclusions. The COVID-19 pandemic had only a modest impact on adherence to endocrine therapy (≈3%), despite the enormous disruptions for patients, the healthcare system in general, and cancer care in particular that were occurring in that period. [ABSTRACT FROM AUTHOR]

Simple Summary: For centrally located non-small cell lung cancer (NSCLC), sleeve lobectomy would be preferable to pneumonectomy (PN). In this context, however, the role of complex sleeve lobectomy (CLS) is still poorly understood. Our study compared CLS with PN using a retrospective analysis. Research shows that CLS has a lower 90-day mortality rate and fewer major complications compared to PN, while oncological outcomes remain comparable. These results support the contention that CLS is a safe and effective procedure for centrally located NSCLC, even after neoadjuvant treatment. Background: Standard sleeve lobectomies are recommended over pneumonectomy (PN), but the efficacy and oncological proficiency of complex sleeve lobectomies (CSLs) have not been completely investigated. The aim of this study was to report our experience in CSL in patients affected by a centrally located non-small-cell lung cancer (NSCLC), comparing all the variables and outcomes with PN. Methods: From 2014 to 2022, we collected the data of patients who underwent PN and CSL for NSCLC, excluding neuroendocrine tumors, salvage surgery or carinal resection. Regression analysis was used to assess the association between procedures and complications; the Kaplan–Meier method and Cox regression analysis were used to evaluate survival and risk factors of reduced survival. Results: We analyzed n = 38 extended sleeve lobectomies and n= 6 double-sleeve lobectomies (CSL group) and n= 60 PNs. We had a trend toward higher postoperative mortality in the PN group (5% vs. 0%, p = 0.13). Major complications and bronchial fistula developed in 21.7% and 6.8% (p = 0.038) and in 6.7% and 4.5% (p = 0.64), respectively. The right side was identified as risk factor for major complications, whereas age > 70 and PN had a trend of association in multivariable analysis. The median OS was similar between the two groups (p = 0.76) and cancer recurrence was the only significant risk factors of reduced OS. Excluding functionally compromised patients, the OS of CSL was better than that of PN (67% vs. 42%, p = 0.25). Conclusions: Considering that major complications are often associated with mortality after surgery for centrally located NSCLC, CSLs could be considered an alternative to PN while also ensuring comparable survival. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we reviewed and analyzed various radiomics models used to identify three of the most common pediatric posterior fossa tumors: medulloblastoma, pilocytic astrocytoma, and ependymoma. We wanted to understand how well these models worked overall. By examining a range of studies, we found that the models could effectively distinguish between these tumor types with high accuracy. Certain types of models and specific features in the images seemed to perform better. The findings suggest that these models can be very useful in accurately diagnosing these pediatric brain tumors. This research could lead to even more precise models in the future. Purpose: To better define the overall performance of the current radiomics-based models for the discrimination of pediatric posterior fossa tumors. Methods: A comprehensive literature search of the databases PubMed, Ovid MEDLINE, Ovid EMBASE, Web of Science, and Scopus was designed and conducted by an experienced librarian. We estimated overall sensitivity (SEN) and specificity (SPE). Event rates were pooled across studies using a random-effects meta-analysis, and the χ2 test was performed to assess the heterogeneity. Results: Overall SEN and SPE for differentiation between MB, PA, and EP were found to be promising, with SEN values of 93% (95% CI = 0.88–0.96), 83% (95% CI = 0.66–0.93), and 85% (95% CI = 0.71–0.93), and corresponding SPE values of 87% (95% CI = 0.82–0.90), 95% (95% CI = 0.90–0.98) and 90% (95% CI = 0.84–0.94), respectively. For MB, there is a better trend for LR classifiers, while textural features are the most used and the best performing (ACC 96%). As for PA and EP, a synergistic employment of LR and NN classifiers, accompanied by geometrical or morphological features, demonstrated superior performance (ACC 94% and 96%, respectively). Conclusions: The diagnostic performance is high, making radiomics a helpful method to discriminate these tumor types. In the forthcoming years, we expect even more precise models. [ABSTRACT FROM AUTHOR]

Simple Summary: Understanding the time it takes for sarcoma patients to start treatment after their diagnosis is essential, as a rapid onset of therapy could mean better survival chances. Sarcomas, which are rare and complex cancers, often require swift and specialized care. Our study delved into this time period, known as time-to-treatment initiation (TTI), across a variety of sarcoma cases using detailed, real-world-time data. We found that the length of TTI can differ significantly depending on the type of sarcoma and where the patients receive care. Notably, our comprehensive data collection process has shown that reported TTI using RWTD reflects a thorough account of the patient's experience from diagnosis to treatment start, which is crucial for developing a healthcare system that focuses on delivering value-based care. The insights from our analysis pinpoint where improvements are needed and how specialized sarcoma centers can better coordinate care to start treatment promptly, especially for those cases where early intervention is critical. Benchmarking is a fundamental tool for enhancing quality within a patient-centered healthcare framework. This study presents an analysis of time-to-treatment initiation (TTI) for sarcoma patients, utilizing a database encompassing 266 cases from the Swiss Sarcoma Network. Our findings indicate a median TTI of 30 days across the cohort, with bone sarcomas and deep soft tissue sarcomas demonstrating a shorter median TTI of 28 days, followed by superficial soft tissue sarcomas at 42 days. The data reveal that the use of real-world-time data (RWTD) may account for a longer TTI observed, as it offers more comprehensive capture of patient journeys, unlike conventional datasets. Notably, variability in TTI was observed between different treatment institutions, which underscores the need for standardized processes across centers. We advocate for a selective referral system to specialized centers to prevent capacity overload and ensure timely treatment initiation. Our analysis also identified significant delays in TTI for unplanned 'whoops'-resections, highlighting the importance of early specialist referral in optimizing treatment timelines. This study emphasizes the potential benefits of a streamlined, data-informed approach to sarcoma care. However, further research is required to establish the direct impact of integrated care models on TTI and patient outcomes in the context of sarcoma treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: This study group has previously published and documented that multimodal prehabilitation (enhanced optimization of physical function and adjustment of modifiable medical issues) before major bladder surgery is feasible and leads to a positive change in patients' fitness and functional status from a short-term perspective after surgery. However, long-term follow-ups after prehabilitation have not yet been published. Thus, this study aims to evaluate 1-year results on the efficacy of physical prehabilitation on functional capacity and nutritional recovery to inform the bladder cancer community of the potential of prehabilitation. The results show that prehabilitation in major bladder cancer surgery can significantly improve physical function and support the maintenance of nutritional status one year after major bladder cancer surgery. The results promote the gradual recognition that early restoration of physical function is vital to a full recovery. Multimodal prehabilitation is the process of enhancing physiological, nutritional, and psychological resilience to increase patients' functional capacity before major cancer surgery and aims to empower the patient to withstand the pending stress of major surgery and ultimately to improve long-term outcomes. The effect of physical prehabilitation to counteract the physical decline in surgical cancer patients has been documented; however, long-term results have not yet been published. This follow-up study aims to evaluate 1-year results on the efficacy of physical prehabilitation after bladder cancer surgery. The efficacy of prehabilitation was measured over the course of 1 year in 107 patients randomized to (1) pre- and rehabilitation or (2) standard care divided by n = 50 in the intervention (I) and n = 57 in the standard group (S). Physical function was measured by muscle leg power, and nutritional status was expressed with handgrip strength. Prehabilitation in major bladder cancer surgery can significantly improve physical function with 19.8 Watt/kg (p = 0.04), lean body mass (p = 0.047) and body cell mass (p = 0.03), and regained nutritional status one year after surgery. The results demonstrate that the restoration of physical function is vital to a full recovery. [ABSTRACT FROM AUTHOR]

Simple Summary: Anatomical variants are traits that differ between individuals. The sphenoid bone has numerous variant features, such as foramina and canals, that may be involved in surgical procedures. This study on CT-scan images describes the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal and their relationships. For the first time, a correlation between the foramen of Vesalius and the canaliculus innominatus was found. This topic is especially important in cranial base surgical procedures that may involve tumor treatment. The sphenoid bone presents several anatomical variations, including accessory foramina, such as the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal, which may be involved in tumor invasion or surgery of surrounding structures. Therefore, clinicians and surgeons have to consider these variants when planning surgical interventions of the cranial base. The prevalence of each variant is reported in the published literature, but very little information is available on the possible correlation among different variants. Here, 300 CT scans of patients (equally divided among males and females) were retrospectively assessed to investigate the presence of the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal. Possible differences in the prevalence of each accessory foramen according to sex were assessed, as well as possible correlations among different variants through the Chi-square test (p < 0.01). Overall, the prevalence of the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal was 30.7%, 67.7%, 14.0% and 35.3%, respectively, without any difference according to sex (p > 0.01). A significant positive correlation was found between the foramen of Vesalius and canaliculus innominatus, both in males and in females (p < 0.01). In detail, subjects with canaliculus innominatus in 85.7–100.0% of cases also showed the foramen of Vesalius, independently from sex and side. The present study provided novel data about the prevalence of four accessory foramina of the sphenoid bone in an Italian population, and a correlation between the foramen of Vesalius and the canaliculus innominatus was found for the first time. As these accessory foramina host neurovascular structures, the results of this study are thus useful for appropriate planning surgical procedures that are tailored to the anatomical configuration of the patient and for improving techniques to avoid accidental injuries in cranial base surgery. Knowledge of the topography, frequencies and the presence/absence of these additional foramina are pivotal for a successful procedure. Clinicians and surgeons may benefit from these novel data for appropriate recognition of the variants, decision-making, pre-operative and treatment planning, improvement of the procedures, screening of patients and prevention of misdiagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Research suggests that a skin condition called atopic dermatitis (AD) and cancer, specifically kidney cancer, might be connected. However, we do not have enough evidence to confirm this link. This study aimed to determine whether the risk is real and whether the severity of AD influences this association. We used a big database of health information from Korea for the investigation and found that people with moderate to severe AD have a higher-than-average chance of getting kidney cancer. This discovery could help doctors better understand these conditions and might lead to more frequent check-ups for kidney cancer in people with AD, especially those with severe disease. Background: Evidence for an association between atopic dermatitis (AD) and cancer is still insufficient. In particular, the association between the risk of renal malignancy and the severity of AD has not been thoroughly investigated. Objective: To investigate the risk of renal malignancy and determine the association between AD severity and cancer risk using data from the Korean National Health Insurance Service (KNHIS) database. Methods: We performed a population-based cohort study using the National Health Claims database from the NHIS in Korea. Results: We found a statistically significant association between AD and overall malignancy (for mild AD, hazard ratio (HR): 1.061, 95% confidence interval (CI): 1.006–1.118; for moderate to severe AD, HR: 1.061, 95% CI: 1.014–1.11) compared with the no AD group. The moderate to severe AD group showed a significantly increased risk for renal malignancy (adjusted HR: 1.533, 95% CI: 1.209–1.944) compared with the no AD group. Limitations: Patient inclusion is solely based on diagnostic codes. We had no data about drug use, genetic factors, or other medical history that could affect the cancer risk. Conclusion: In our large population-based cohort study, moderate to severe AD was associated with increased risk of renal malignancy. Regular check-ups for renal malignancy are recommended in this population. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigated the optimal SMI cutoff to discriminate overall survival (OS) in a cohort of consecutive advanced HNSCC patients. Untailored, BMI-tailored and gender-tailored cutoffs were analyzed, and gender-tailored SMI categorization had the highest prognostic value, which was retained in a multivariate analysis including several HNSCC-specific prognostic factors. (1) Background: Sarcopenia lasting >1 year might be considered a chronic condition in many HNSCC patients. CT-scan-derived Skeletal Muscle Mass Index (SMI) is an established surrogate of sarcopenia; yet, the cut-off reported in the literature (literature-based, lb-SMI < 43.2) is mainly based on the risk of chemoradiotherapy-induced toxicity, and the optimal value to discriminate OS is under-investigated. (2) Methods: The effect on OS of the lb-SMI cutoff was compared with an untailored OS-oriented SMI cutoff obtained in a cohort of consecutive advanced HNSCC patients treated with primary chemoradiotherapy, bio-chemotherapy or chemo-immunotherapy (cohort-specific, cs-SMI cutoff). Gender- and BMI-tailored (gt-SMI and bt-SMI) cut-offs were also evaluated. Cutoff values were identified by using the maximally selected rank statistics for OS. (3) Results: In 115 HNSCC patients, the cs-SMI cutoff was 31.50, which was lower compared to the lb-SMI reported cut-off. The optimal cut-off separately determined in females, males, overweight and non-overweight patients were 46.02, 34.37, 27.32 and 34.73, respectively. gt-SMI categorization had the highest effect on survival (p < 0.0001); its prognostic value was independent of the treatment setting or the primary location and was retained in a multivariate cox-regression analysis for OS including other HNSCC-specific prognostic factors (p = 0.0004). (4) Conclusions: A tailored SMI assessment would improve clinical management of sarcopenia in chemoradiotherapy-, bio-chemotherapy- or chemo-immunotherapy-treated HNSCC patients. Gender-based SMI could be used for prognostication in HNSCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study was to assess the influence of the COVID-19 pandemic on the diagnosis and treatment of head and neck cancer (HNC) patients between 2018 and 2022. We analysed the medical records of 625 patients. During the COVID-19 pandemic, compared with the pre-COVID-19 pandemic period, the duration of the cancer diagnostic process was significantly longer, the proportion of patients admitted on the basis of a DILO card issued by a primary care physician was significantly higher, and the majority of cancer patients with a planned oncological treatment lived in urban areas. The aim of this study was to identify and assess the impact of the COVID-19 pandemic on the diagnosis and treatment of head and neck cancer (HNC) patients of the Department of Otolaryngology, Head and Neck Surgery of the 4th Military Teaching Hospital in Wroclaw for whom oncological treatment was planned by a cancer case board between March 2018 and February 2022. We analysed the medical records of 625 patients. In order to verify whether the relationships between the analysed features were statistically significant, the chi-square test of independence and the Student's t-test for independent samples were used (p < 0.05). Our analysis showed that the impact of the pandemic on the organization of health service delivery to HNC patients was not uniform. The largest difference in the number of formulated treatment plans was observed at the beginning of the pandemic (22.1% reduction compared with the year before the pandemic). During the pandemic, the proportion of patients admitted on the basis of a DILO (diagnosis and oncological treatment) card issued by a primary care physician, instead of a regular referral to hospital, issued also by a primary care physician, was significantly higher compared with the that during the pre-pandemic period. The majority of cancer patients with a oncological treatment planned during the pandemic lived in urban areas. During the pandemic, the number of patients with more-advanced-stage cancer, assessed on the basis of the type of planned treatment (radical vs. palliative), did not increase compared with that during the pre-pandemic period. However, our follow-up period was quite short. It is necessary to intensify activities aimed at promoting health and increasing health awareness in people living in rural areas and setting long-term priorities and objectives for health policies at the national, regional and local levels, with particular focus on this group of people. [ABSTRACT FROM AUTHOR]

Simple Summary: Melanoma is a type of skin cancer that develops from melanocytes (the cells that give the skin its brown color). Subungual melanoma (nail melanoma) is a rare type of malignant melanoma that arises beneath the nails. Subungual melanoma has been categorized as a type of acral melanoma, which occurs on the hands and feet. Using a genetic study, we found that subungual melanoma showed molecular features that were different from those of acral melanoma. Subungal melanoma had a frequently mutated gene, named G protein subunit alpha Q. Patients with subungual melanoma show better survival than patients with acral melanoma. We suggest that subungual melanoma should be considered as a type of melanoma that is separate from acral melanoma. The genetic evaluation of subungual melanoma is important for advanced cancer patients, so that appropriate targeted therapy may be selected. Subungual melanoma (SUM) is a rare type of malignant melanoma that arises beneath the nails. SUM is categorized as a type of acral melanoma (AM), which occurs on the hands and feet. SUM is an aggressive type of cutaneous melanoma that is most common among Asian patients. Recent studies reveal that SUM and AM might have different molecular characteristics. Treatment of melanoma relies on analysis of both clinical and molecular data. Therefore, the clinical and molecular characteristics of SUM need to be established, especially during metastasis. To define the mutation profiles of SUM and compare them with those of AM, we performed next-generation sequencing of primary and metastatic tumors of SUM and AM patients. Subungual location was a better independent prognostic factor than acral location for better overall survival (p = 0.001). Patients with SUM most commonly had the triple wild-type (75%) driven by GNAQ (58%) and KIT (25%) mutations, whereas patients with AM had BRAF (28.6%) and RAF (14.3%) molecular types of mutations. Single-nucleotide variations (SNVs) were more common in SUM than in AM, whereas copy number alterations (CNAs) were more common metastatic lesions of AM. Metastatic tumors in patients with SUM and AM showed increases in CNAs (43% and 80%, respectively), but not in SNVs. The number of CNAs increased during metastasis. When compared with AM, SUM has distinct clinical and molecular characteristics. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aims to examine the association between nasopharyngeal carcinoma and human papillomavirus infections by means of a nationwide population-based study. This study included 2747 individuals aged 20 years and older who were diagnosed with nasopharynx cancer as cases and 13,735 propensity-score-matching controls. The chi-squared test indicated a significant dissimilarity in previous human papillomavirus infection rates between nasopharynx cancer patients and controls (12.7% vs. 7.2%, p < 0.001). The adjusted odds ratio for prior human papillomavirus infections was found to be significantly higher for nasopharyngeal carcinoma cases compared to controls at a value of 1.869 with confidence interval ranging from 1.640 to 2.128 (p < 0.001). Our study indicates a noteworthy association between previous human papillomavirus infections and nasopharyngeal carcinoma. Healthcare providers should consider patients' history of human papillomavirus infection when evaluating their susceptibility to nasopharyngeal carcinoma. This population-based study aims to examine the association between nasopharyngeal carcinoma and human papillomavirus infections. This study included 2747 individuals aged 20 years and older who were diagnosed with nasopharynx cancer as cases and 13,735 propensity-score-matching controls. Multivariate logistic regression models were employed to quantitatively assess the association of nasopharynx cancer with human papillomavirus infections while considering age, sex, monthly income, geographic location, and urbanization level of the patient's residence as well as diabetes, hypertension, and hyperlipidemia. Our chi-squared test indicated a significant dissimilarity in previous human papillomavirus infection rates between nasopharynx cancer patients and controls (12.7% vs. 7.2%, p < 0.001). The adjusted odds ratio (OR) for prior human papillomavirus infections was found to be significantly higher for nasopharyngeal carcinoma cases compared to controls at a value of 1.869 with confidence interval ranging from 1.640 to 2.128. Among female participants, compared to controls, the adjusted OR of prior human papillomavirus infections was 2.150 (95% CI = 1.763–2.626) in patients with nasopharynx cancer. In male participants sampled in this study, we observed a statistically significant association between prior human papillomavirus infections and nasopharynx cancer (adjusted OR = 1.689; 95% CI = 1.421–2.008). Our study indicates a noteworthy association between previous human papillomavirus infections and nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: In our study, which started with the hypothesis that there is a histopathological marker that can be used to predict prognosis in oral squamous cell carcinomas, we found that tumor budding is quite significant. The fact that this finding will provide us with very important data in routine practice and play a key role in the treatment management of patients will be a significant finding and contribution to the literature. The utility of histological grading, which is useful in predicting prognosis in many tumors, is controversial for oral squamous cell carcinoma (OSCC). Therefore, new histopathological parameters should be added to histopathology reports of OSCCs. The study aimed to evaluate the parameters of worst invasion pattern (WPOI) and tumor budding in patients with OSCC, to compare them with other histopathological parameters, clinical data and overall survival, and to evaluate these results within the literature. A total of 73 OSCC cases with excisional biopsies were included in this study. WPOI, tumor budding, cell nest size, tumor-stroma ratio, stromal lymphocyte infiltration and stroma type, as well as classical histopathological parameters, were evaluated on hematoxylin-eosin-stained sections. Perineural invasion, lymph node metastases, advanced stage, presence of more than five buds and single cell invasion pattern in univariate survival analyses are characterized by a shortened overall survival time. While there was no significant difference between WPOI results and survival in the survival analysis, WPOI 5 was associated with more frequent lymph node metastasis and advanced stage at the time of diagnosis compared to WPOI 4. We concluded that tumor budding and single-cell invasion should be considered prognostic histopathologic parameters in OSCC. [ABSTRACT FROM AUTHOR]

Simple Summary: In this two-part study, we assessed the risk factors associated with FN. On top of commonly associated risk factors such as age and body mass index, we found that there are ethnic differences in terms of FN incidence. Notably, patients of non-Chinese ethnicity had a higher FN incidence. This trend remained significant even after multiple adjustments with other patients, tumors, and treatment characteristics. Further analysis exploring differences across ethnicities revealed that Indian patients were more likely to experience greater dips in absolute neutrophil count during chemotherapy and Malay patients were more likely to be administered with anthracyclines, both of which contribute to higher FN risk. Importantly, we also found that non-Chinese patients were more likely to experience multiple FN episodes during chemotherapy. Additional research is needed to investigate the possibility of pharmacogenetic differences across these ethnicities. The majority of published findings on chemotherapy-induced febrile neutropenia (FN) are restricted to three ethnic groups: Asians, Caucasians, and African Americans. In this two-part study, we examined FN incidence and risk factors in Chinese, Malay, and Indian chemotherapy-treated breast cancer (BC) patients. Hospital records or ICD codes were used to identify patients with FN. In both the Singapore Breast Cancer Cohort (SGBCC) and the Joint Breast Cancer Registry (JBCR), the time of the first FN from the start of chemotherapy was estimated using Cox regression. Multinomial regression was used to evaluate differences in various characteristics across ethnicities. FN was observed in 170 of 1014 patients in SGBCC. The Cox model showed that non-Chinese were at higher risk of developing FN (HRMalay [95% CI]:2.04 [1.44–2.88], p < 0.001; HRIndian:1.88 [1.11–3.18], p = 0.018). In JBCR, FN was observed in 965 of 7449 patients. Univariable Cox models identified ethnicity, a lower baseline absolute neutrophil count, non-luminal A proxy subtypes, and anthracycline-containing regimens as risk factors. Disparities across ethnicities' risk (HRMalay:1.29 [1.07–1.54], p = 0.006; HRIndian:1.50 [1.19–1.88], p < 0.001) remained significant even after further adjustments. Finally, an age-adjusted multinomial model showed that Malays (p = 0.006) and Indians (p = 0.009) were significantly more likely to develop multiple episodes of FN during treatment. Ethnic differences in chemotherapy-induced FN among BC patients exist. Further studies can focus on investigating pharmacogenetic differences across ethnicities. [ABSTRACT FROM AUTHOR]

Simple Summary: There is a broad variety of treatment options for lung cancer, which include medical therapy and surgical resection. Opinion varies as to the optimal treatment options and combinations in different contexts of the disease, which has an impact on the prognosis of the disease—relapse and survival. This is a descriptive study on patients who underwent multimodality therapy (a combination of chemotherapy, radiotherapy and surgical resection) and an evaluation of patient and disease characteristics that may have an impact on the treatment pathway. Lung cancer remains the leading cause of cancer deaths in the United Kingdom. For locally advanced disease, multimodality treatment is recommended, which includes a combination of chemotherapy, radiotherapy, surgery and, more recently immunotherapy. Options depend on the resectability of the cancer and there has been debate about the optimal treatment strategy: surgery may be planned to follow chemoradiotherapy (CRT), be offered for residual disease after CRT, or given as salvage therapy for patients treated with CRT who have later relapse of their disease. We conducted a retrospective analysis of all patients who underwent CRT and surgical resection under a single surgical team and performed a descriptive study after dividing the patients into these three groups. For the planned trimodality group, 30-day mortality this was 7% (n = 1) and 1-year survival was 78.6%; the residual disease group had a 30-day mortality rate of 0% and 1-year survival of 81.3%; for the salvage group, the figures were 0% and 62.5%, respectively. The median overall survival of the study population was 35.8 months. Median overall survival in the trimodality group was 35.4 months (20.1–51.7 interquartile range IQR), for the residual group was 34.2 months (18.5–61.0 IQR). and for the salvage group was 35.8 months (32.4–52.7 IQR).) [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer (PCa) represents the most common male urologic neoplasia. In the present study, the authors performed a review of scientific literature to establish the most potentially valuable biomarkers. After this a meta-analysis of two most interesting biomarkers (BRCA 1 and 2 and ctDNA) has been performed to evaluate their utility for the diagnostics, treatment, and prognosis of prostate cancer. The obtained results can help select the best diagnostic tool for early prostate diagnosis. To date, no ideal PCa biomarker has been found. Although BRCA1 and BRCA2 work well for breast and ovarian cancers, they do not seem to be reliable for prostate cancer. In our opinion, ctDNA seems to be a very promising biomarker, but still more research in this field is needed. Prostate cancer represents the most common male urologic neoplasia. Tissue biopsies are the gold standard in oncology for diagnosing prostate cancer. We conducted a study to find the most reliable and noninvasive diagnostic tool. We performed a systematic review and meta-analysis of two biomarkers which we believe are the most interesting: BRCA (BRCA1 and 2) and ctDNA. Our systematic research yielded 248 articles. Forty-five duplicates were first excluded and, upon further examination, a further 203 articles were excluded on the basis of the inclusion and exclusion criteria, leaving 25 articles. A statistical analysis of the obtained data has been performed. With a collective calculation, BRCA1 was expressed in 2.74% of all cases from 24,212 patients examined and BRCA2 in 1.96% of cases from 20,480 patients. In a total calculation using ctDNA, it was observed that 89% of cases from 1198 patients exhibited high expression of circulating tumor DNA. To date, no ideal PCa biomarker has been found. Although BRCA1 and BRCA2 work well for breast and ovarian cancers, they do not seem to be reliable for prostate cancer. ctDNA seems to be a much better biomarker; however, there are few studies in this area. Further studies need to be performed. [ABSTRACT FROM AUTHOR]

Simple Summary: In the present work on metastatic breast cancer patients, we studied liquid biopsy samples to analyze different biomarkers, such as circulating tumor cells, leukocytes, and platelets. We observed a correlation between a higher number of circulating tumor cells and a greater probability of detecting clusters and megakaryocytes among the patients. This observation was independent of the breast cancer subtype. We also confirmed the presence of megakaryocytes in the peripheral blood of cancer patients, which is an unusual finding. In addition, a higher pan-inflammatory value, calculated by dividing the product of neutrophils, monocytes, and platelets by the number of lymphocytes, was associated with lower overall survival, providing insight into the depth of the metastatic process. Liquid biopsy is becoming an important source of new biomarkers during the treatment of metastatic cancer patients. Using size-based microfluid technology, we isolated circulating tumor cells (CTCs) from metastatic breast cancer patients to evaluate their presence and cluster formation, as well as the presence of megakaryocytes and immune-inflammatory blood cells, and to correlate their presence with clinicopathological data and overall survival (OS). In total, 59 patients (median age 60.4 years) were included in the study: 62.7% luminal A/B-like, 20.3% HER2-positive, and 17% triple-negative. Our results showed that at least one CTC was present in 79.7% and ≥5 CTCs in 35.2% of the patients. CTC clusters were present in patients with ≥5 CTCs only (in 19.2% of them), and megakaryocytes were present in 52% of all patients. The presence of CTC clusters and megakaryocytes was positively associated with the CTC count. Patients with low pan-inflammatory value (PIV), low systemic immune-inflammatory index (SII), and low relative change from baseline (ΔPIV%, ΔSII%) were associated with significantly higher OS than their counterparts. ΔPIV%, the presence of infection in the last month, and a long duration of metastatic disease were identified as independent prognostic factors for OS. The interplay of CTCs, CTC clusters, megakaryocytes, and PIV needs to be further explored. [ABSTRACT FROM AUTHOR]

Simple Summary: Electrochemotherapy has proven to be an efficient treatment for cutaneous metastases of various cancers including breast cancer (BC). The large number of patients collected within the INSPECT database provides the possibility of a differentiated analysis on BC with different receptor statuses (estrogen receptor and HER2 receptor). Patients with BC presenting cutaneous metastases were retrieved from the INSPECT database and divided by their receptor status: HER2+, HR+ (ER/PgR+), and TN (triple negative). ECT treatment is equally effective among groups, despite different conditions, age, time since diagnosis, previous or concomitant treatments, and treatment characteristics. Response and local tumor control seem to be better in multiple small lesions than in big armor-like lesions, suggesting that treating smaller, even multiple, lesions at the time of occurrence is more effective than treating bigger long-lasting armor-like cutaneous lesions. Electrochemotherapy has been proven to be an efficient treatment for cutaneous metastases of various cancers. Data on breast cancer (BC) patients with cutaneous metastases were retrieved from the INSPECT database. Patients were divided by their receptor status: HER2+, HR+ (ER/PgR+), and TN (triple negative). Groups were similar for histological subtype and location of the nodules. Most patients were previously treated with surgery/systemic therapy/radiotherapy. We found no differences in the three groups in terms of response ratio (OR per patient 86% HER2+, 80% HR+, 76% TN, p = 0.8664). The only factor positively affecting the complete response rate in all groups was small tumor size (<3 cm, p = 0.0105, p = 0.0001, p = 0.0266, respectively). Local progression-free survival was positively impacted by the achievement of complete response in HER2+ (p = 0.0297) and HR+ (p = 0.0094), while overall survival was affected by time to local progression in all groups (p = 0.0065 in HER2+, p < 0.0001 in HR+, p = 0.0363 in TN). ECT treatment is equally effective among groups, despite different receptor status. Response and local tumor control seem to be better in multiple small lesions than in big armor-like lesions, suggesting that treating smaller, even multiple, lesions at the time of occurrence is more effective than treating bigger long-lasting armor-like cutaneous lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: Robot-assisted prostatectomy is one of the main therapeutic options for localized prostate cancer. Lymphoceles are one of the major causes of complications after robot-assisted radical prostatectomy and pelvic lymph node dissection. Because the data on risk factors for lymphoceles remains unclear and inconclusive, they were investigated in the present study using the data set of the prospective randomized trial ProLy. In this study, high BMI was found to be an independent predictor for the occurrence of lymphoceles and symptomatic lymphoceles. In addition, a longer surgical time proved to be another risk factor for the postoperative occurrence of lymphoceles. Lymphoceles (LC) occur in up to 60% after robot-assisted radical prostatectomy (RARP) and pelvic lymphadenectomy (PLND). In 2–10%, they are symptomatic and may cause complications and require treatment. Data on risk factors for the formation of lymphoceles after RARP and PNLD remain sparse in the urologic literature and are inconclusive to date. The underlying data of this secondary analysis were obtained from the prospective multi-center RCT ProLy. We performed a multivariate analysis to focus on the potential risk factors that may influence lymphocele formation. Patients with LC had a statistically significant higher BMI (27.8 vs. 26.3 kg/m2, p < 0.001; BMI ≥ 30 kg/m2: 31 vs. 17%, p = 0.002) and their surgical time was longer (180 vs. 160 min, p = 0.001) In multivariate analysis, the study group (control vs. peritoneal flap, p = 0.003), BMI (metric, p = 0.028), and surgical time (continuous, p = 0.007) were independent predictors. Patients with symptomatic lymphocele presented with higher BMI (29 vs. 26.6 kg/m2, p = 0.007; BMI ≥ 30 kg/m2: 39 vs. 20%, p = 0.023) and experienced higher intraoperative blood loss (200 vs. 150 mL, p = 0.032). In multivariate analysis, BMI ≥ 30 kg/m2 vs. < 30 kg/m2 was an independent predictor for the formation of a symptomatic lymphocele (p = 0.02). High BMI and prolonged surgical time are general risk factors for the development of LC. Patients with a BMI ≥ 30 kg/m2 had a higher risk for symptomatic lymphoceles. [ABSTRACT FROM AUTHOR]