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Simple Summary: The prognosis of PCa at diagnosis is assessed by classification systems that aim to group homogenous sets of patients. However, great heterogeneity exists within these risk groups, in terms of prognostic factors and treatment options. The aim of this study was to assess the prognostic impact and predictors of adverse tumor grade in very favorable low- and intermediate-risk prostate cancer patients treated with robot-assisted radical prostatectomy at a high-volume tertiary referral center. Objectives: To assess the prognostic impact and predictors of adverse tumor grade in very favorable low- and intermediate-risk prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP). Methods: Data of low- and intermediate PCa risk-class patients were retrieved from a prospectively maintained institutional database. Adverse tumor grade was defined as pathology ISUP grade group > 2. Disease progression was defined as a biochemical recurrence event and/or local recurrence and/or distant metastases. Associations were assessed by Cox's proportional hazards and logistic regression model. Results: Between January 2013 and October 2020, the study evaluated a population of 289 patients, including 178 low-risk cases (61.1%) and 111 intermediate-risk subjects (38.4%); unfavorable tumor grade was detected in 82 cases (28.4%). PCa progression, which occurred in 29 patients (10%), was independently predicted by adverse tumor grade and biopsy ISUP grade group 2, with the former showing stronger associations (hazard ratio, HR = 4.478; 95% CI: 1.840–10.895; p = 0.001) than the latter (HR = 2.336; 95% CI: 1.057–5.164; p = 0.036). Older age and biopsy ISUP grade group 2 were independent clinical predictors of adverse tumor grade, associated with larger tumors that eventually presented non-organ-confined disease. Conclusions: In a very favorable PCa patient population, adverse tumor grade was an unfavorable prognostic factor for disease progression. Active surveillance in very favorable intermediate-risk patients is still a hazard, so molecular and genetic testing of biopsy specimens is needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Most cancer patients are older and have concomitant diseases because the incidence of most cancer types increases with age. This leads to patients taking a variety of medications that can cause drug-related problems (DRPs). DRPs can cause harm, including increased illness, avoidable hospital stays, and even death. Common DRPs are drug–drug interactions, not taking medication as prescribed, and adverse drug reactions. In our study, we aimed to assess these medication risks in hospitalized cancer patients and to identify factors that influence their health-related quality of life (HRQOL) as a patient-relevant outcome. The results of the pharmacist-led medication reviews show that DRPs are common in hospitalized cancer patients. Therefore, patient questionnaires about therapy-related symptoms could improve the detection of DRPs. While drug-related factors had no effect on HRQOL during the hospital stay, our analysis revealed other influencing factors, such as relapse status of the cancer disease and length of hospital stay. Background: We aimed to assess medication risks and determine factors influencing the health-related quality of life (HRQOL) in cancer inpatients. Methods: A retrospective analysis was conducted to identify drug-related problems (DRPs) based on medication reviews, including patient-reported outcomes (PROs). Multiple linear regression analyses were performed to identify sociodemographic, disease-related, and drug therapy-related factors influencing changes from hospital admission to discharge in the scales of the EORTC QLQ-C30 questionnaire. Results: A total of 162 inpatients with various hematological and solid cancer diseases was analyzed. Patients received a mean of 11.6 drugs and 92.6% of patients exhibited polymedication resulting in a mean of 4.0 DRPs per patient. Based on PRO data, 21.5% of DRPs were identified. Multiple linear regression models described the variance of the changes in global HRQOL and physical function in a weak-to-moderate way. While drug therapy-related factors had no influence, relapse status and duration of hospital stay were identified as significant covariates for global HRQOL and physical function, respectively. Conclusion: This analysis describes underlying DRPs in a German cancer inpatient population. PROs provided valuable information for performing medication reviews. The multiple linear regression models for global HRQOL and physical function provided explanations for changes during hospital stay. [ABSTRACT FROM AUTHOR]

Simple Summary: PD-L1 expression determines patients' eligibility for immunotherapy. Current sampling does not consider the heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) within the primary tumor. Moreover, potential differences are not considered when comparing primary tumors and their associated metastases or local recurrences, hereby excluding potential responders to immunotherapy. Here, we investigated the inter-sample heterogeneity of PD-L1 expression by analyzing multiple samples from individual patients. Multisection staining revealed clinically relevant CPS changes, which would have potentially affected treatment decisions in 28.7% (intra-tumoral), 44.4% (tumor vs. metastases), and 61.5% (initial tumor vs. local recurrence) of patients, respectively, compared with single-region staining. Increased CPS in primary tumors and lymph node metastases were associated with improved 5-year overall survival. Our results suggest that multiple tumor sections should be evaluated in HNSCC patients when assessing PD-L1 expression prior to potential immunotherapy, particularly if the initial result was negative. For practical reasons, in many studies PD-L1 expression is measured by combined positive score (CPS) from a single tumor sample. This does not reflect the heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma (HNSCC). We investigated the extent and relevance of PD-L1 expression heterogeneity in HNSCC analyzing primary tumors and recurrences (LRs), as well as metastases. Tumor tissue from 200 HNSCC patients was immunohistochemically stained for PD-L1 and analyzed using image-analysis software QuPath v3.4 with multiple specimens per patient. CPS was ≥20 in 25.6% of primary tumors. Intra-tumoral heterogeneity led to a therapeutically relevant underestimation of PD-L1 expression in 28.7% of patients, when only one specimen per patient was analyzed. Inter-tumoral differences in PD-L1 expression between primary tumors and lymph node metastasis (LNM) or LR occurred in 44.4% and 61.5% (CPS) and in 40.6% and 50% of cases (TPS). Overall survival was increased in patients with CPS ≥ 1 vs. CPS < 1 in primary tumors and LNM (hazard ratio: 0.46 and 0.35; p < 0.005); CPS in LR was not prognostic. Our analysis shows clinically relevant intra- and inter-sample heterogeneity of PD-L1 expression in HNSCC. To account for heterogeneity and improve patient selection for immunotherapy, multiple sample analyses should be performed, particularly in patients with CPS/TPS < 1. [ABSTRACT FROM AUTHOR]

Simple Summary: Vulvar lymphomas are uncommon diseases and account for less than 0.5% of gynecological cancers and 1.5% of all NHLs. The various types of lymphomas have recently been identified as separate diseases and not as morphological variations of the same disease, according to the World Health Organization classification. They often represent the secondary localization of systemic disease, and diffuse large B-cell lymphoma is the most common type. We also considered cases of vulvar T-cell lymphomas. The data analysis highlighted the difficulty of diagnosis and the need to resort to biopsy–histological examination, as well as molecular methods. The correctness of the diagnosis directly affects appropriate therapeutic management, which requires an adequate surgical approach that can be integrated with chemotherapy and radiotherapy. Since they are very rare tumors, lymphomas of the vulva are often not properly recognized. Patients with vulvar lymphoma are generally elderly and the classical manifestation of the disease is a vulvar mass. No significant age differences have been found between primary and secondary lymphoma. To make a correct diagnosis, it is therefore necessary to use not only histological examination but also the genetic and molecular profile in order to establish optimal therapeutic management. Literature analysis confirm the good prognosis of this disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiotherapy to the prostate with curative intent was previously a procedure that was delivered over seven and a half weeks. The standard of care is now 20 treatments over 4 weeks; however, 5 treatments have recently been shown to be as good as 20 treatments in patients with intermediate risk disease. Fewer treatments mean that patients spend less time in the hospital and travelling to appointments and helps to reduce the burden on radiotherapy departments. When reducing the number of treatments, the dose per treatment is increased. This requires greater precision and certainty of dose delivery. The magnetic resonance linear accelerator (MRL) delivers radiotherapy under MRI guidance with the ability to modify the plan to adapt to any changes in the patient's anatomy, thus potentially enabling the safe delivery of higher doses per treatment. This study addresses the true dose delivered in two and five treatments of the MRL and whether target objects are being met. HERMES is a phase II trial of MRI-guided daily-adaptive radiotherapy (MRIgART) randomising men with localised prostate cancer to either 2-fractions of SBRT with a boost to the tumour or 5-fraction SBRT. In the context of this highly innovative regime the dose delivered must be carefully considered. The first ten patients recruited to HERMES were analysed in order to establish the dose received by the targets and organs at risk (OARS) in the context of intrafraction motion. A regression analysis was performed to measure how the volume of air within the rectum might further impact rectal dose secondary to the electron return effect (ERE). One hundred percent of CTV target objectives were achieved on the MRI taken prior to beam-on-time. The post-delivery MRI showed that high-dose CTV coverage was achieved in 90% of sub-fractions (each fraction is delivered in two sub-fractions) in the 2-fraction cohort and in 88% of fractions the 5-fraction cohort. Rectal D1 cm3 was the most exceeded constraint; three patients exceeded the D1 cm3 < 20.8 Gy in the 2-fraction cohort and one patient exceeded the D1 cm3 < 36 Gy in the 5-fraction cohort. The volume of rectal gas within 1 cm of the prostate was directly proportional to the increase in rectal D1 cm3, with a strong (R = 0.69) and very strong (R = 0.90) correlation in the 2-fraction and 5-fraction cohort respectively. Dose delivery specified in HERMES is feasible, although for some patients delivered doses to both target and OARs may vary from those planned. [ABSTRACT FROM AUTHOR]

Simple Summary: The United States is suffering from an epidemic associated with infections with the Human Papilloma Virus (HPV) that are responsible for the development of head and neck squamous cell carcinoma (HNSCC). Our study aims to characterize immune profiles, and the oral microbiota in oropharyngeal tumors associated with anti-PD-1 treatment response in a preclinical murine model for HPV+ oropharyngeal cancer. We confirmed 16 immune markers and specific bacteria in the oral cavity that differentiate between treatment responders and non-responders, which may be used as potential biomarkers for PD-1 blockade response. The United States is suffering from an epidemic associated with high-risk strains of the Human Papillomavirus (HPV) predominantly responsible for the development of head and neck squamous cell carcinoma (HNSCC). Treatment with immune checkpoint inhibitors targeting programmed death 1 (PD-1) or its ligand PD-L1 has shown poor efficacy in HNSCC patients, observing only a 20–30% response. Therefore, biological marker identification associated with PD-1 blockade response is important to improve prognosis and define novel therapeutics for HNSCC patients. Therapy response was associated with increased frequencies of activated CD27+T cells, activated CD79a+ B cells, antigen-presenting CD74+ dendritic and B cells, and PD-L1+ and PD-L2+ myeloid-derived suppressor cells (MDSCs). The oral microbiota composition differed significantly in mice bearing tongue tumors and treated with anti-PD-1. A higher abundance of Allobaculum, Blautia, Faecalibacterium, Dorea, or Roseburia was associated with response to the therapy. However, an increase in Enterococcus was attributed to tongue tumor-bearing non-responding mice. Our findings indicate that differences in immune phenotypes, protein expression, and bacterial abundance occur as mice develop tongue tumors and are treated with anti-PD-1. These results may have a clinical impact as specific bacteria and immune phenotype could serve as biomarkers for treatment response in HNSCC. [ABSTRACT FROM AUTHOR]

Simple Summary: The impact of a prior cervical excisional procedure on the oncologic outcomes of patients with early-stage cervical cancer undergoing radical hysterectomy is not established. Smaller retrospective studies suggest that conization prior to the performance of radical hysterectomy may be associated with lower risk of tumor relapse, especially for patients undergoing minimally invasive hysterectomy. We utilized a large hospital-based database and identified patients with FIGO 2009 stage IB1 disease who had primary surgical treatment. Approximately one in three patients had a prior excisional procedure performed within 3 months of radical surgery. We demonstrated that the performance of an excisional procedure prior to radical hysterectomy may be associated with better overall survival. For patients who had a prior excisional procedure, minimally invasive surgery was not associated with worse overall survival compared to laparotomy even after controlling for confounders. Objective: To investigate the impact of a prior cervical excisional procedure on the oncologic outcomes of patients with apparent early-stage cervical carcinoma undergoing radical hysterectomy. Methods: The National Cancer Database (2004–2015) was accessed, and patients with FIGO 2009 stage IB1 cervical cancer who had a radical hysterectomy with at least 10 lymph nodes (LNs) removed and a known surgical approach were identified. Patients who did and did not undergo a prior cervical excisional procedure (within 3 months of hysterectomy) were selected for further analysis. Overall survival (OS) was evaluated following the generation of Kaplan–Meier curves and compared with the log-rank test. A Cox model was constructed to control a priori-selected confounders. Results: A total of 3159 patients were identified; 37.1% (n = 1171) had a prior excisional procedure. These patients had lower rates of lymphovascular invasion (29.2% vs. 34.9%, p = 0.014), positive LNs (6.7% vs. 12.7%, p < 0.001), and a tumor size >2 cm (25.7% vs. 56%, p < 0.001). Following stratification by tumor size, the performance of an excisional procedure prior to radical hysterectomy was associated with better OS even after controlling for confounders (aHR: 0.45, 95% CI: 0.30, 0.66). The rate of minimally invasive surgery was higher among patients who had a prior excisional procedure (61.5% vs. 53.2%, p < 0.001). For these patients, performance of minimally invasive radical hysterectomy was not associated with worse OS (aHR: 1.37, 95% CI: 0.66, 2.82). Conclusions: For patients undergoing radical hysterectomy, preoperative cervical excision may be associated with a survival benefit. For patients who had a prior excisional procedure, minimally invasive radical hysterectomy was not associated with worse overall survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is a life-threatening disease of the liver. Patients who also have a blockage of the portal vein, which takes blood into the liver, are at particular risk for death. This condition is known as portal vein tumor thrombosis (PVTT). Proton beam therapy (PBT) is an excellent treatment option for tumors because it allows the tumor to be irradiated while avoiding radiation effects on normal tissue. In this study, we found that the long-term outcomes in patients with HCC with advanced PVTT (Vp3 or Vp4) were improved by treatment with PBT. In particular, the median survival time after was >20 months in patients treated with PBT for cure of the disease. These results are better than those with other therapies and suggest that PBT gives a survival benefit in these cases. There were also very few adverse events, indicating that PBT is a safe method. Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) has a poor prognosis and is generally not indicated for surgery. Proton beam therapy (PBT) may offer an alternative treatment. In this study, long-term outcomes were examined in 116 patients (median age 66 years, 100 males) with HCC with advanced PVTT (Vp3 or Vp4) who received PBT from April 2008 to March 2018. Of these patients, 63 received PBT as definitive treatment and 53 as palliative treatment. The representative dose was 72.6 Gy (RBE) in 22 fractions. Eight patients died in follow-up, including 72 due to tumor progression. The 5-year overall survival (OS) rate was 18.0% (95% CI 9.8–26.2%) and the 5-year local control (LC) rate was 86.1% (74.9–97.3%). In multivariate analyses, performance status and treatment strategy were significantly associated with OS. The median follow-up period for survivors with definitive treatment was 33.5 (2–129) months, and the 5-year OS rate was 25.1% (12.9–37.3%) in these cases. The median survival time after definitive irradiation was >20 months. The 5-year OS rate was 9.1% (0–19.7%) for palliative irradiation. These results compare favorably with those of other therapies and suggest that PBT is a useful option for cases of HCC with advanced PVTT that cannot undergo surgery, with an expected survival benefit and good local control. Determining the optimal indication for this treatment is a future challenge. [ABSTRACT FROM AUTHOR]

Simple Summary: The present study aimed to evaluate the age-related distribution of HPV 16/18 genotypes and non-16/18 HPV genotypes in unvaccinated women. CIN3 in women younger than 30 years was significantly associated with HPV16/18 genotypes. The surprising fact of the present study is represented by the fact that in women under the age of 30, almost 90% of CIN3 cases were associated with HPV16/18, while CIN3 with non-16/18 HPV genotypes develops slowly and in older age. The data from the present study suggest that the risk of CIN3 is related to the woman's age and hr HPV genotype. These data are essential to optimize current and future screening programs. Background. The objective of the present study is to investigate the age-specific distribution of HPV genotypes in CIN3 lesions in screened unvaccinated women. These data are essential to optimize current and future screening programs. Methods. A multicenter retrospective study was conducted. A total of 408 unvaccinated women with positive histology and a high-risk HPV genotype were enrolled. Each woman at baseline had HPV DNA testing and HPV genotyping, and all women underwent targeted biopsy and/or treatment with a loop electrosurgical excision procedure (LEEP) before entering the study. We divided the genotypes into HPV16/18 and HPV non-16/18 (HPV31/33/45/35/39/51/52/58/59/66/68). Women were divided into increasing age categories: <30, 30–44, and ≥45. Results. The percentage of CIN3 associated with HPV16/18 is maximum in women under 30 years of age (85.1%), drops to 75.6% in women aged between 30 and 44 years, and up to 47.2% in women over 45 years. CIN3 in women younger than 30 years was significantly associated with HPV16/18 genotypes (p = 0). Discussion. The data from the present study suggest that the risk of CIN3 is related to the woman's age and hr HPV genotype. The data highlight two different types of CIN3: a more frequent type, related to HPV16/18, which develops rapidly and in young women, and another, relating to non-16/18 HPV, which develops later at an advanced age and slowly, through low-grade lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: Mutation of the SMARCB1 gene can cause one of the most aggressive and lethal cancers of early childhood and infancy, malignant rhabdoid tumor (MRT). Despite the standard multimodal therapy (resection, conventional chemotherapy, and radiotherapy), the outlook for young children with MRT is poor. For infants, the disease can also preclude the use of radiotherapy. Numerous experimental treatments explore epigenetic mechanisms, but the DNA damage response has not yet been extensively evaluated as a therapeutic approach for MRT. We report a new therapeutic strategy for SMARCB1-deficient MRTs, combining PARP1 inhibition and DNA damage induction. The observed synergy between the PEGylated PARP1 inhibitor talazoparib (PEG~TLZ) and the DNA alkylating agent temozolomide (TMZ) may lead to improved therapeutic strategies for patients with this challenging cancer. We identified a new potential biomarker of response to PEG~TLZ+TMZ, O6-methylguanine methyltransferase (MGMT), and uncovered dysregulated signaling pathways involved in the response. Additionally, we elucidated the pro-survival role of SMARCB1 loss in MRT cells. Malignant rhabdoid tumors (MRTs) are among the most aggressive and treatment-resistant malignancies affecting infants, originating in the kidney, brain, liver, and soft tissues. The 5-year event-free survival rate for these cancers is a mere 20%. In nearly all cases of MRT, the SMARCB1 gene (occasionally SMARCA4)—a pivotal component of the SWI/SNF chromatin remodeling complex—is homozygously deleted, although the precise etiology of these tumors remains unknown. While young patients with localized MRT generally show improved outcomes, especially those who are older and have early-stage disease, the overall prognosis remains poor despite optimal standard treatments. This highlights the urgent need for more effective treatment strategies. We investigated the antitumor activity of a PARP1 inhibitor (talazoparib, TLZ) combined with a DNA alkylating agent (temozolomide, TMZ) in MRT xenograft models. PARP1 is a widely targeted molecule in cancer treatment and, beyond its role in DNA repair, it participates in transcriptional regulation by recruiting chromatin remodeling complexes to modulate DNA accessibility for RNA polymerases. To widen the therapeutic window of the drug combination, we employed PEGylated TLZ (PEG~TLZ), which has been reported to reduce systemic toxicity through slow drug release. Remarkably, our findings indicate that five out of six MRT xenografts exhibited an objective response to PEG~TLZ+TMZ therapy. Significantly, the loss of SMARCB1 was found to confer a protective effect, correlating with higher expression levels of DNA damage and repair proteins in SMARCB1-deficient MRT cells. Additionally, we identified MGMT as a potential biomarker indicative of in vivo MRT response to PEG~TLZ+TMZ therapy. Moreover, our analysis revealed alterations in signaling pathways associated with the observed antitumor efficacy. This study presents a novel and efficacious therapeutic approach for MRT, along with a promising candidate biomarker for predicting tumor response. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aims to improve the preoperative classification of nerve sheath tumors using radiomics, a method that extracts quantitative data from medical images. By analyzing MRI scans, we seek to develop a more accurate way to distinguish between different types of nerve sheath tumors before surgery. Our findings could lead to better treatment planning and outcomes for patients with these tumors. This research has the potential to enhance the diagnostic process and contribute to more personalized care for individuals with nerve sheath tumors, ultimately benefiting the medical community and patients alike. Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue tumors prevalent in neurofibromatosis type 1 (NF1) patients, posing a significant risk of metastasis and recurrence. Current magnetic resonance imaging (MRI) imaging lacks decisiveness in distinguishing benign peripheral nerve sheath tumors (BPNSTs) and MPNSTs, necessitating invasive biopsies. This study aims to develop a radiomics model using quantitative imaging features and machine learning to distinguish MPNSTs from BPNSTs. Clinical data and MRIs from MPNST and BPNST patients (2000–2019) were collected at a tertiary sarcoma referral center. Lesions were manually and semi-automatically segmented on MRI scans, and radiomics features were extracted using the Workflow for Optimal Radiomics Classification (WORC) algorithm, employing automated machine learning. The evaluation was conducted using a 100× random-split cross-validation. A total of 35 MPNSTs and 74 BPNSTs were included. The T1-weighted (T1w) MRI radiomics model outperformed others with an area under the curve (AUC) of 0.71. The incorporation of additional MRI scans did not enhance performance. Combining T1w MRI with clinical features achieved an AUC of 0.74. Experienced radiologists achieved AUCs of 0.75 and 0.66, respectively. Radiomics based on T1w MRI scans and clinical features show some ability to distinguish MPNSTs from BPNSTs, potentially aiding in the management of these tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: Achieving margins of >5 mm is challenging in the larynx and hypopharynx because resections are constrained by their complex anatomy. The aim of this study was to retrospectively assess the clinical relevance of resection margins defined by the RCP in total laryngectomies (TLs) and total laryngopharyngectomies (TLPs). Similar survival rates for close and clear margins for primary and recurrent LSCC were found. This may suggest that a margin > 5 mm is not clinically relevant in terms of survival, therefore a margin of 1–5 mm should be accepted in certain subsites. Margins < 1 mm are related to significantly worse outcomes and should be avoided. Background: Laryngeal and hypopharyngeal cancer is complex and resection margins are therefore constrained. The aim of this study was to investigate the clinical relevance of resection margins in laryngeal and hypopharyngeal surgery. Methods: A retrospective cohort study was performed for patients treated with a total laryngectomy (TL) or laryngopharyngectomy (TLP) for laryngeal or hypopharyngeal squamous cell carcinoma (LSCC and HSCC, respectively). Within the groups primary LSCC, recurrent LSCC, primary HSCC, and recurrent HSCC the relationship between the status of the resection margin according to the Royal Collage of Pathology and the recurrence and survival rates were investigated. Results: Positive resection margins were found in 54% for primary LSCC, 29% for recurrent LSCC, 62% for primary HSCC, and 44% for recurrent HSCC. For primary and recurrent LSCC, there was a linear association between total recurrence and narrowing margins (p = 0.007 resp. p = 0.008). Multivariate survival analysis for primary and recurrent LSCC showed a significantly worse disease free and disease-specific survival in case of positive margins compared to clear margins. Conclusion: Similar survival rates were recorded for close and clear margins for primary and recurrent LSCC. This may suggest that a margin > 5 mm is not clinically relevant in terms of survival. Therefore, a margin of 1–5 mm should be accepted in certain subsites. Margins < 1 mm are related to significantly worse outcomes and should be avoided. [ABSTRACT FROM AUTHOR]

Simple Summary: Helicobacter pylori (H. Pylori) eradication has been the mainstream for preventing and treating gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Prior studies have shown variations in the eradication rates of H. Pylori in the US. This can influence gastric MALT lymphoma occurrence and outcomes. Therefore, we conducted a comprehensive analysis of incidence and mortality rates of gastric MALT lymphoma in different demographic-specific populations. We found that gastric MALT lymphoma incidence rates have been decreasing in the US over the past two decades. This decline was observed in both sexes, various age groups, and all race/ethnic populations except Black individuals. The decrease was also seen in early-stage tumors but not in late-stage tumors. Mortality analysis showed decreasing mortality in males, older adults, early-stage tumors, and most race/ethnic groups but not in females, younger adults, Black individuals, or late-stage tumors, which had non-decreasing rates. Our findings hold important public health implications and encourage further investigations of gastric MALT lymphoma risk factors, including disparities in H. Pylori screening, management, and outcomes. Background: Helicobacter pylori (H. Pylori) eradication has been the mainstream for preventing and treating gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Prior data showed disparities in eradication rates of H. Pylori between different populations. This can potentially impact the occurrence of gastric MALT lymphoma. There are limited data on the incidence and mortality rates and trends of gastric MALT lymphoma in the US. Therefore, the aim of the current study was to conduct a time-trend analysis of gastric MALT lymphoma incidence and mortality rates in different populations. Methods: The incidence rates of gastric MALT lymphoma were calculated from the United States Cancer Statistics (USCS) database (which covers nearly 98% of the US population) between 2001–2020 and were age-adjusted to the standard 2000 US population using SEER*Stat software (version 8.4.3, national cancer institute "NCI"). Incidence-based mortality (IBM) rates, also age-adjusted to the standard 2000 US population, were calculated from the Surveillance Epidemiology and End Results (SEER) database. Tumor location was specified using ICD-O-3 codes C 160–C 169 with malignant behavior. Histopathology was specified using the ICD-O-3 code 9699. The rates were categorized by sex, age, race/ethnicity, and tumor stage at diagnosis. Age groups were older adults (aged 55 years or older) and younger adults (aged younger than 55 years). Race/ethnic groups included Non-Hispanic White (White), Non-Hispanic Black (Black), Hispanic, Non-Hispanic Asian/Pacific Islander (API), and Non-Hispanic American Indian/Alaska Native (AI/AN), as reported in the database. Stage at diagnosis included early stage (in situ and localized tumors) and late stage (regional and distant site tumors). Joinpoint Regression Software (version 5.0.2, NCI) using the weighted Bayesian Information Criteria method was used to generate time trends. Trends were reported as annual percentage change (APC) and average APC (AAPC). Parametric estimations were used with a two-sided t-test to evaluate the trends with a p-value cutoff at 0.05. Results: There were 21,625 patients diagnosed with gastric MALT lymphoma in the US between 2001 and 2020. Overall, incidence rates were significantly decreasing over the study period (AAPC = −1.93). This decrease was seen in males (AAPC = −1.67) and in females (AAPC = −1.66) (Figure). When categorized by age groups, older adults also experienced a significant decrease in gastric MALT lymphoma incidence rates (AAPC = −1.66). While this was also seen in younger adults, the rates were decreasing at a slower pace (AAPC = −1.38). When categorizing the trends by race/ethnicity, incidence rates were significantly decreasing in White (AAPC = −2.09), Hispanic (AAPC = −1.61), and API (AAPC = −3.92) populations. However, the rates were stable among Blacks. While early-stage tumors experienced a significant decrease (AAPC = −1.10), the rates were stable for late-stage tumors. When evaluating mortality, there were 11,036 patients whose death was attributed to gastric MALT lymphoma between 2000 and 2020. IBM rates were decreasing in males (AAPC = −1.47), older adults (AAPC = −1.55), Whites (AAPC = −1.23), Hispanics (AAPC = −1.73), APIs (AAPC = −2.30), and early-stage tumors (AAPC = −1.08). On the other hand, IBM rates were stable in females, younger adults, Blacks, and late-stage tumors. Discussion: An extensive nationwide data analysis encompassing nearly 98% of patients diagnosed with gastric MALT lymphoma in the US unveils a declining trend in the incidence of cancer overall over the past two decades. This decline is observed in both sexes and various age groups. When stratifying by race and ethnicity, this incidence has been decreasing in all populations except among Black individuals. While early-stage tumors have also demonstrated a significant decrease in incidence rates, late-stage tumors have shown no parallel decline. Mortality evaluation also revealed an improvement in most of the US population except among females, younger adults, Black individuals, and late-stage tumors. While the cause of our findings is unclear, it could be driven by disproportionate exposure to risk factors, including H. Pylori, and disparities in screening, management, and outcomes. Future studies are warranted to investigate factors contributing to worse outcomes of gastric MALT lymphoma, especially in the Black population. [ABSTRACT FROM AUTHOR]

Simple Summary: Functional MRI has become established in the surgery of brain metastases (BM) as a preoperative diagnostic tool to identify intact eloquent cortex areas. Evidence shows that by allowing surgeons to spare these intraoperatively, patients' postoperative outcome is improved in terms of significantly reduced mortality and morbidity. The influence specifically of BM on the fMRI signal and brain networks has scarcely been investigated, as most studies to date refer only to primary brain tumors or include various tumor entities. Our work examined how BM affect cortical activation and brain networks using task-based fMRI. We found a qualitative attenuation of patients' fMRI signal in the metastasis-affected hemisphere compared to the contralateral hemisphere and alterations in all examined brain networks of the patients compared to healthy controls, and also in the contralateral hemisphere. Thus, our results provide insights into the behavior of BM during fMRI examination and their impact on the integrity of the brain. To date, there are almost no investigations addressing functional connectivity (FC) in patients with brain metastases (BM). In this retrospective study, we investigate the influence of BM on hemodynamic brain signals derived from functional magnetic resonance imaging (fMRI) and FC. Motor-fMRI data of 29 patients with BM and 29 matched healthy controls were analyzed to assess percent signal changes (PSC) in the ROIs motor cortex, premotor cortex, and supplementary motor cortex and FC in the sensorimotor, default mode, and salience networks using Statistical Parametric Mapping (SPM12) and marsbar and CONN toolboxes. In the PSC analysis, an attenuation of the BOLD signal in the metastases-affected hemisphere compared to the contralateral hemisphere was significant only in the supplementary motor cortex during hand movement. In the FC analysis, we found alterations in patients' FC compared to controls in all examined networks, also in the hemisphere contralateral to the metastasis. This indicates a qualitative attenuation of the BOLD signal in the affected hemisphere and also that FC is altered by the presence of BM, similarly to what is known for primary brain tumors. This transformation is not only visible in the infiltrated hemisphere, but also in the contralateral one, suggesting an influence of BM beyond local damage. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is the most common gynecological cancer. However, advanced and recurrent cancers are less sensitive to chemotherapy and have poor prognoses. Therefore, new treatment strategies are being explored. Recently, immune checkpoint inhibitors (ICIs) have been used in treating various cancers. Although AT-rich interaction domain 1A (ARID1A) negativity has been proposed as a new biomarker for immune checkpoint inhibitors, there have been no reports on ARID1A biomarkers in endometrial cancer. Therefore, we investigated whether ARID1A negativity predicts the efficacy of ICIs in treating endometrial cancer. We assessed ARID1A expression and tumor-infiltrating lymphocytes (CD8+) and immune checkpoint molecules (PD-L1/PD-1) using immunostaining and MSI analysis. Throughout our experiment, CD8 and PD-1 expression did not differ significantly between the ARID1A-negative and ARID1A-positive groups. Our findings suggest that ARID1A negativity may not be a suitable biomarker for ICI efficacy in endometrial cancer. Background: AT-rich interaction domain 1A (ARID1A) has been proposed as a new biomarker for predicting response to immune checkpoint inhibitors (ICIs). The predictive value of ARID1A for predicting ICI effectiveness has not been reported for endometrial cancer. Therefore, we investigated whether ARID1A negativity predicts ICI effectiveness for endometrial cancer treatment. Methods: We evaluated ARID1A expression, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1/PD-1) by immunostaining endometrial samples from patients with endometrial cancer. Samples in which any of the four mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) were determined to be negative via immunostaining were excluded. In the ARID1A-negative group, microsatellite instability (MSI) status was confirmed via MSI analysis. Results: Of the 102 samples investigated, 25 (24.5%) were ARID1A-negative. CD8 and PD-1 expression did not differ significantly between the ARID1A-negative group and the ARID1A-positive group; however, the ARID1A-negative group showed significantly lower PD-L1 expression. Only three samples (14.2%) in the ARID1A-negative group showed high MSI. Sanger sequencing detected three cases of pathological mutation in the MSH2-binding regions. We also established an ARID1A-knockout human ovarian endometriotic epithelial cell line (HMOsisEC7 ARID1A KO), which remained microsatellite-stable after passage. Conclusion: ARID1A negativity is not suitable as a biomarker for ICI effectiveness in treating endometrial cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: The VELOUR randomized phase III trial established aflibercept (an anti-angiogenic targeting VEGF-A, VEGF-B, and placenta growth factor) combined with FOLFIRI as an effective treatment in patients with metastatic colorectal cancer (mCRC) failing a prior oxaliplatin-based regimen. This real-world study mandated by Polish Health Authorities aimed at assessing the benefits/risks of aflibercept plus FOLFIRI prescribed to Polish patients with mCRC according to reimbursement criteria. The activity of aflibercept plus FOLFIRI in such patients was confirmed, and no new safety signal was reported. Background: This was an observational study prospectively evaluating the effectiveness and safety of aflibercept/FOLFIRI administered in second-line mCRC per the reimbursement criteria in Poland. Methods: Consecutive mCRC patients who progressed with first-line oxaliplatin-based chemotherapy received aflibercept (4 mg/kg IV) followed by FOLFIRI every 2 weeks until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); overall survival (OS) and safety were the secondary endpoints. Results: A total of 93 patients were treated at 17 Polish sites. A median of 10 cycles was administered. Over a median treatment duration of 5.3 months, median PFS and median OS were 8.4 months [95% CI, 6.9–9.9] and 27.0 months [95% CI, 23.9–30.1], respectively. There was no significant impact of primary tumor location, metastatic site, or KRAS status on PFS and OS. Main grade ≥ 3 adverse events were neutropenia (16%), hypertension (8%), diarrhea (4%), and stomatitis (4%). Conclusions: The benefits/risks of Aflibercept plus FOLFIRI administered per the Polish reimbursement criteria in second-line treatment of mCRC after failure of a prior oxaliplatin-based regimen is confirmed. [ABSTRACT FROM AUTHOR]

Simple Summary: BET proteins (BRD2, BRD3, BRD4 and BRDT) serve as the readers of DNA acetylation and regulate the expression of key genes in cancer. BET inhibitors were recently developed and have shown efficacy in Phase I/II clinical trials in ovarian cancer. The most thoroughly studied BET protein is BRD4, which is amplified in ~18–19% of ovarian cancer cases according to The Cancer Genome Atlas (TCGA). We explored the prognostic role of the BRD4 gene and protein expression in advanced high-grade serous ovarian carcinoma (HGSC). Low BRD4 gene expression was associated with shorter overall survival compared to intermediate/high BRD4 gene expression at 12 months (95% CI; 1.75–30.49; p = 0.008). Low BRD4 gene expression was also associated with worse progression-free survival (PFS) both at 12 months (95% CI; 1.2–16.5; p = 0.03) and at 24 months (95% CI; 1.1–8.6; p = 0.048). There was no significant association between BRD4 protein expression and overall survival. Background: Bromodomain and extra-terminal (BET) domain proteins that bind to acetylated lysine residues of histones serve as the "readers" of DNA acetylation. BRD4 is the most thoroughly studied member of the BET family and regulates the expression of key oncogenes. BRD4 gene amplification has been identified in ovarian cancer (~18–19%) according to The Cancer Genome Atlas (TCGA) analysis. BET inhibitors are novel small molecules that displace BET proteins from acetylated histones and are currently tested in Phase I/II trials. We here aim to explore the prognostic role of the BRD4 gene and protein expression in the ascitic fluid of patients with advanced FIGO III/IV high-grade serous ovarian carcinoma (HGSC). Methods: Ascitic fluid was obtained from 28 patients with advanced stage (FIGO III/IV) HGSC through diagnostic/therapeutic paracentesis or laparoscopy before the initiation of chemotherapy. An amount of ~200 mL of ascitic fluid was collected from each patient and peripheral blood mononuclear cells (PBMCs) were isolated. Each sample was evaluated for BRD4 and GAPDH gene expression through RT-qPCR and BRD4 protein levels through enzyme-linked immunosorbent assay (ELISA). The study protocol was approved by the Institutional Review Board of Alexandra University Hospital and the Committee on Ethics and Good Practice (CEGP) of the National and Kapodistrian University of Athens (NKUA). Results: Low BRD4 gene expression was associated with worse prognosis at 12 months compared to intermediate/high expression (95% CI; 1.75–30.49; p = 0.008). The same association was observed at 24 months although this association was not statistically significant (95% CI; 0.96–9.2; p = 0.065). Progression-free survival was shorter in patients with low BRD4 gene expression at 12 months (5.6 months; 95% CI; 2.6–8.6) compared to intermediate/high expression (9.8 months; 95% CI; 8.3–11.3) (95% CI; 1.2–16.5; p = 0.03). The same association was confirmed at 24 months (6.9 months vs. 13.1 months) (95% CI; 1.1–8.6; p = 0.048). There was a trend for worse prognosis in patients with high BRD4 protein levels versus intermediate/low BRD4 protein expression both at 12 months (9.8 months vs. 7.6 months; p = 0.3) and at 24 months (14.2 months vs. 16.6 months; p = 0.56) although not statistically significant. Again, there was a trend for shorter PFS in patients with high BRD4 protein expression although not statistically significant both at 12 months (p = 0.29) and at 24 months (p = 0.47). Conclusions: There are contradictory data in the literature over the prognostic role of BRD4 gene expression in solid tumors. In our study, intermediate/high BRD4 gene expression was associated with a favorable prognosis in terms of overall survival and progression-free survival compared to low BRD4 gene expression. [ABSTRACT FROM AUTHOR]

Simple Summary: The treatment options for children with recurrent medulloblastoma are often limited due to extensive previously received treatments after initial diagnosis. Especially, repeated radiotherapy is associated with significant side-effects. In this study, we study the impact on survival of repeated radiotherapy at recurrence for patients with previous irradiation, as well as first irradiation at recurrence when no previous radiotherapy was applied. We find that repeated radiotherapy provides a short-time benefit in terms of survival, but survival ten years after recurrence is not significantly improved. At the same time, we find that applying radiotherapy at recurrence when patients received no previous irradiation did significantly improve survival, both short and long term. Background: Radiotherapy (RT) involving craniospinal irradiation (CSI) is important in the initial treatment of medulloblastoma. At recurrence, the re-irradiation options are limited and associated with severe side-effects. Methods: For pre-irradiated patients, patients with re-irradiation (RT2) were matched by sex, histology, time to recurrence, disease status and treatment at recurrence to patients without RT2. Results: A total of 42 pre-irradiated patients with RT2 were matched to 42 pre-irradiated controls without RT2. RT2 improved the median PFS [21.0 (CI: 15.7–28.7) vs. 12.0 (CI: 8.1–21.0) months] and OS [31.5 (CI: 27.6–64.8) vs. 20.0 (CI: 14.0–36.7) months]. Concerning long-term survival after ten years, RT2 only lead to small improvements in OS [8% (CI: 1.4–45.3) vs. 0%]. RT2 improved survival most without (re)-resection [PFS: 17.5 (CI: 9.7–41.5) vs. 8.0 (CI: 6.6–12.2)/OS: 31.5 (CI: 27.6–NA) vs. 13.3 (CI: 8.1–20.1) months]. In the RT-naïve patients, CSI at recurrence improved their median PFS [25.0 (CI: 16.8–60.6) vs. 6.6 (CI: 1.5–NA) months] and OS [40.2 (CI: 18.7–NA) vs. 12.4 (CI: 4.4–NA) months]. Conclusions: RT2 could improve the median survival in a matched cohort but offered little benefit regarding long-term survival. In RT-naïve patients, CSI greatly improved their median and long-term survival. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores the potential of the relative wash-in rate (rWIR) in dynamic contrast-enhanced MRI as a prognostic factor for event-free survival (EFS) in osteosarcoma patients. Eighty-two patients were retrospectively included, and rWIR was determined based on preoperative imaging. Patients with rWIR < 2.3 were considered to have a poor radiological response, while those with rWIR ≥ 2.3 had a good response. This study identified that poor radiological response (rWIR < 2.3) was associated with shorter EFS, even when adjusted for traditional prognostic factors. The 2- and 5-year EFS rates for patients with rWIR ≥ 2.3 were 85% and 75%, compared to 55% and 50% for those with rWIR < 2.3. The findings suggest that the predicted poor chemo response with MRI is associated with shorter EFS and shows similar results to histological response evaluation. rWIR is a potential tool for future response-based individualized healthcare in osteosarcoma patients. Background: The decreased perfusion of osteosarcoma in dynamic contrast-enhanced (DCE) MRI, reflecting a good histological response to neoadjuvant chemotherapy, has been described. Purpose: In this study, we aim to explore the potential of the relative wash-in rate as a prognostic factor for event-free survival (EFS). Methods: Skeletal high-grade osteosarcoma patients, treated in two tertiary referral centers between 2005 and 2022, were retrospectively included. The relative wash-in rate (rWIR) was determined with DCE-MRI before, after, or during the second cycle of chemotherapy (pre-resection). A previously determined cut-off was used to categorize patients, where rWIR < 2.3 was considered poor and rWIR ≥ 2.3 a good radiological response. EFS was defined as the time from resection to the first event: local recurrence, new metastases, or tumor-related death. EFS was estimated using Kaplan–Meier's methodology. Multivariate Cox proportional hazard model was used to estimate the effect of histological response and rWIR on EFS, adjusted for traditional prognostic factors. Results: Eighty-two patients (median age: 17 years; IQR: 14–28) were included. The median follow-up duration was 11.8 years (95% CI: 11.0–12.7). During follow-up, 33 events occurred. Poor histological response was not significantly associated with EFS (HR: 1.8; 95% CI: 0.9–3.8), whereas a poor radiological response was associated with a worse EFS (HR: 2.4; 95% CI: 1.1–5.0). In a subpopulation without initial metastases, the binary assessment of rWIR approached statistical significance (HR: 2.3; 95% CI: 1.0–5.2), whereas its continuous evaluation demonstrated a significant association between higher rWIR and improved EFS (HR: 0.7; 95% CI: 0.5–0.9), underlining the effect of response to chemotherapy. The 2- and 5-year EFS for patients with a rWIR ≥ 2.3 were 85% and 75% versus 55% and 50% for patients with a rWIR < 2.3. Conclusion: The predicted poor chemo response with MRI (rWIR < 2.3) is associated with shorter EFS even when adjusted for known clinical covariates and shows similar results to histological response evaluation. rWIR is a potential tool for future response-based individualized healthcare in osteosarcoma patients before surgical resection. [ABSTRACT FROM AUTHOR]

Simple Summary: Talimogene laherparepvec (TVEC), a modified virus, is a local injected therapy that has been demonstrated to be an effective treatment in patients with advanced melanoma. Recent reports have suggested that radiation treatment (RT) may activate the immune system when combined with TVEC to further improve both local and systemic responses. However, studies on the combined effect of TVEC and RT remain limited. Here, we reviewed twenty melanoma patients who had received TVEC and RT (fourteen patients to the same region and six patients to different regions of the body) and found a benefit in progression-free survival (PFS) and time to distance metastasis (DM) with a combined regional approach of TVEC and RT. These results suggest that the regional approach of using these two treatment modalities may confer a therapeutic benefit. Talimogene laherparepvec (TVEC) is a genetically modified oncolytic herpes simplex virus (HSV-1) that is used for the intralesional treatment of advanced or metastatic melanoma. Given that TVEC produces the granulocyte–macrophage colony-stimulating factor (GM-CSF), recent reports have suggested that radiation treatment (RT) given in conjunction with TVEC may provide synergistic immune activation at the site, and possibly systemically. However, studies on combining RT with TVEC remain limited. We conducted a retrospective review of melanoma patients from a single cancer center who received TVEC and RT in the same region of the body and compared them to patients who received TVEC with RT at another site (other than the site of TVEC injection). Between January 2015 and September 2022, we identified twenty patients who were treated with TVEC and RT; fourteen patients received TVEC and RT in the same region, and six had treatments in separate regions. Regions were determined at the time of analysis and were based on anatomic sites (such as arm, leg, torso, etc.). Kaplan–Meier analysis of progression-free survival (PFS), analyses of time to distant metastasis (DM), overall survival (OS), and locoregional control (LRC), and the corresponding log-rank test were performed. With a median follow-up of 10.5 months [mos] (range 1.0–58.7 mos), we found an improvement in PFS with TVEC and RT in the same region compared to different regions, which were 6.4 mos (95% CI, 2.4–NR mos) and 2.8 mos (95% CI, 0.7–4.4 mos), respectively; p = 0.005. There was also a significant improvement in DM when TVEC and RT were used in the same region compared to different regions: 13.8 mos (95% CI, 4.6–NR mos) and 2.8 mos (95% CI, 0.7–4.4 mos), respectively (p = 0.001). However, we found no difference in overall survival (OS) between patients who had TVEC and RT in the same region (19.0 mos, 95% confidence interval [CI], 4.1–not reached [NR] mos) and those who received treatments in different regions (18.5 mos, 95% CI, 1.0–NR mos); p = 0.366. There was no statistically significant improvement in locoregional control (LRC) in patients who had TVEC and RT in the same region was 26.0 mos (95% CI, 6.4–26.0 mos) compared to patients who received TVEC and RT in different regions (4.4 mos) (95% CI, 0.7–NR mos) (p = 0.115). No grade 3 or higher toxicities were documented in either group. Overall, there were improvements in PFS and DM when TVEC and RT were delivered to the same region of the body compared to when they were used in different regions. However, we did not find a significant difference in locoregional recurrence or OS. Future studies are needed to assess the sequence and timing of combining RT and TVEC to potentially enhance the immune response both locally and distantly. [ABSTRACT FROM AUTHOR]

Simple Summary: Microvesicles (MVs) are essential for inter-cellular signaling in health and disease. We analyzed MV levels in colorectal cancer patients and assessed their release in early-stage colorectal cancer and survival. Considering that all types of MV were elevated beginning in the very early stages of the disease, we believe that the study of circulating MV levels could provide evidence for their use in the early detection of colon cancer in patients. Background: The release of microvesicles (MVs) is an essential phenomenon for inter-cellular signaling in health and disease. The role of MVs in cancer is multidimensional and includes cancer cell survival, proliferation, and invasion. In this prospective study, we analyzed MV levels in colorectal cancer patients and assessed the importance of MV release in early-stage colorectal cancer and survival. Methods: This study included 98 patients and 15 controls. The characterization of MVs from human plasma was performed by flow cytometry using monoclonal antibodies. Results: The levels of total MVs and MUC-1-positive, tissue factor (TF)-positive, and endothelial cell-derived MVs (EMVs) were statistically significantly higher in the colon cancer patients than in the controls (p < 0.001). Furthermore, the subgroup of patients with very early-stage colorectal cancer also had statistically significant differences in the levels of the abovementioned MVs compared to the controls (p < 0.01). Highly differentiated tumors had lower levels of MUC-1-positive MVs (p < 0.02), EMVs (p < 0.002), and EMV/TF combinations (p < 0.001) versus those with tumors with low/intermediate differentiation. Conclusions: Our data demonstrate that the analysis of circulating MV levels in plasma could possibly become a tool for the early diagnosis of colon cancer at a very early stage of the disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Currently, a versatile and useful predictive model for post-hepatectomy liver failure (PHLF) remains elusive. Therefore, this study aimed to develop predictive models for PHLF based on type IV collagen 7s domain (7s collagen) in patients with hepatocellular carcinoma. We retrospectively collected data from 972 patients. PHLF grades B or C were identified in 104 patients (11%): 98 (10%) and 6 (1%) PHLF grades B and C, respectively. The preoperative serum level of 7s collagen was significantly associated with a proportional increase in PHLF risk. A nomogram was developed based on 7s collagen, with a concordance index of 0.768. The inclusion of 7s collagen values in the predictive model increased the prediction accuracy. Our novel nomogram using 7s collagen may be useful for predicting the risk of PHLF. Background: Previous studies have attempted to establish predictive models for post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) undergoing liver resection. However, a versatile and useful predictive model for PHLF remains to be developed. Therefore, we aimed to develop predictive models for PHLF based on type IV collagen 7s domain (7s collagen) in patients with HCC. Methods: We retrospectively collected data from 972 patients with HCC who had undergone initial curative liver resection between February 2000 and December 2020 at our hospital. Multivariate logistic regression analysis using a restricted cubic spline was performed to evaluate the effect of 7s collagen on the incidence of PHLF. A nomogram was developed based on 7s collagen. Results: PHLF grades B or C were identified in 104 patients (11%): 98 (10%) and 6 (1%) PHLF grades B and C, respectively. Multivariate logistic regression analysis revealed that the preoperative serum level of 7s collagen was significantly associated with a proportional increase in the risk of PHLF, which was confirmed in both laparoscopic and open liver resections. A nomogram was developed based on 7s collagen, with a concordance index of 0.768. The inclusion of 7s collagen values in the predictive model increased the predictive accuracy. Conclusion: The findings highlight the efficacy of the serum level of 7s collagen as a predictive factor for PHLF. Our novel nomogram using 7s collagen may be useful for predicting the risk of PHLF. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment of non-muscle invasive bladder cancer (NMIBC) consists mainly of repeated transurethral bladder surgery (TURBs) and instillation treatments. This treatment might influence bladder function and, therefore, the patient's quality of life. We used bladder-related medication as a surrogate marker of compromised bladder function to investigate whether the load of repeated surgery and the exposure to adjuvant instillation influence bladder function. The study was conducted as a register-based study in a non-selected national cohort of NMIBC patients. We included 17,774 patients. Patients exposed to ≥5 TURBs had a higher risk of using bladder-relaxing medication than patients exposed to 1 TURB and a higher risk of cystitis. BCG-exposed patients had a higher risk of bladder-relaxing medication use compared to non-exposed and had a higher risk of cystitis. Repeated TURBs have the highest impact on bladder function. To maintain the best possible bladder function, the goal of NMIBC treatment should be as few TURBs as feasible. Repeated transurethral bladder resections (TURBs) and instillation treatments in non-muscle invasive bladder cancer (NMIBC) might influence bladder function and, therefore, quality of life. Bladder-related medication is a surrogate marker of compromised bladder function. The objective was to investigate whether TURBs and adjuvant instillation therapy are associated with the use of anticholinergics, β3-agonists, and cystitis-relevant antibiotics. We divided all Danish patients diagnosed with primary NMIBC during 2002–2017 registered in the Danish National Patient Registry (DNPR) based on TURB-load within the first five years from diagnosis (1 TURB, 2–4 TURBs, ≥5 TURBs). Instillation therapy with either mitomycin C (MMC) or bacillus Calmette-Guerin vaccine (BCG) was independent exposure (yes or no). We included 17,774 patients; 76% men, median age: 70 years (IQR: 63, 77). Patients exposed to ≥5 TURBs had a higher risk of using bladder-relaxing medication than patients exposed to 1 TURB, HR = 4.01 [3.33; 4.83], and higher risk of cystitis, HR = 2.27 [2.05; 2.51]. BCG-exposed patients had a higher risk of bladder-relaxing medication use compared to non-exposed, HR = 1.92 [1.69; 2.18], and a higher risk of cystitis, HR = 1.39 [1.31; 1.48]. Repeated TURBs have the highest impact on bladder function. Adjuvant instillation therapy is also associated with the use of bladder-related medication. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer disrupts various internal functions, which may be reflected across several blood markers or biomarkers. The precise ratios of these biomarkers could be useful for endometrial cancer diagnosis, prognosis, and treatment decisions. Our study aimed to observe whether a panel of blood markers (red blood cells, white blood cells, platelets, inflammatory markers) managed to distinguish between two endometrial entities (neoplasia versus hyperplasia). Background: Endometrial cancer is associated with changes in blood cell counts and with high levels of inflammatory markers, thus reflecting the tumor's impact on various biological processes and suggesting their potential as biomarkers for endometrial cancer diagnosis, prognosis, and treatment response. The neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio in peripheral blood sampled preoperatively from patients have been reported to be independently associated with the prognosis of different types of malignancies. Objectives: This study aimed to compare several blood markers—red blood cells, white blood cells, platelet parameters, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, C-reactive protein, and fibrinogen—in patients with benign or malignant endometrial tumors. Material and methods: Our retrospective study included 670 patients (192 diagnosed with endometrial cancer and 478 with endometrial hyperplasia), and we compared the serological parameters discussed above with those sampled the day before surgery. Results: Analysis of complete blood count indices revealed no significant differences in red blood cell or total white blood cell parameters between the endometrial cancer group and the endometrial hyperplasia group. However, a distinct pattern emerged in the white blood cell differential. The endometrial cancer group showed a statistically significant decrease in lymphocyte count compared with the endometrial hyperplasia group. In contrast, the endometrial cancer group showed significantly higher mean platelet counts and increased mean platelet volume compared with controls. Furthermore, the endometrial cancer group demonstrated a marked inflammatory response, as evidenced by significantly elevated levels of C-reactive protein, fibrinogen, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio compared with the endometrial hyperplasia group. Conclusions: The current research revealed statistically significant differences in multiple serological biomarkers between the two groups. These findings support the initial hypothesis regarding the potential utility of these biomarkers in endometrial cancer diagnosis, prognosis, and treatment response, highlighting the existence of biomarkers affordable for analysis under any health system, regardless of the country's level of development. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal disease in gastric cancer has a poor prognosis, with a median survival of 3–6 months and a 5-year survival rate of 0%. Despite multiple advancements in therapeutics, the National Comprehensive Cancer Network (NCCN) guidelines recommend systemic chemotherapy or best supportive care for GC with peritoneal dissemination. According to several studies, CRS + HIPEC could provide survival advantages in gastric cancer peritoneal metastasis compared to pSC. Background: Peritoneal carcinomatosis is one of deadliest metastatic patterns of gastric cancer, being associated with a median overall survival (OS) of 4 months. Up to now, palliative systemic chemotherapy (pSC) has been the only recommended treatment. The aim of this study is to evaluate a potential survival benefit after CRS + HIPEC compared to pSC. Methods: A systematic review was conducted according to the PRISMA guidelines in March 2024. Manuscripts reporting patients with peritoneal carcinomatosis from gastric cancer treated with CRS + HIPEC were included. A meta-analysis was performed, comparing the survival results between the CRS + HIPEC and pSC groups, and the primary outcome was the comparison in terms of OS. We performed random-effects meta-analysis of odds ratios (ORs). We assessed heterogeneity using the Q2 statistic. Results: Out of the 24 papers included, 1369 patients underwent CRS + HIPEC, with a median OS range of 9.8–28.2 months; and 103 patients underwent pSC, with a median OS range of 4.9–8 months. CRS + HIPEC was associated with significantly increased survival compared to palliative systemic chemotherapy (−1.8954 (95% CI: −2.5761 to −1.2146; p < 0.001). Conclusions: CRS + HIPEC could provide survival advantages in gastric cancer peritoneal metastasis compared to pSC. [ABSTRACT FROM AUTHOR]

Simple Summary: Lymphoceles (lymphatic fluid collections in the pelvis) are a common complication of robot-assisted radical prostatectomy. Peritoneal interposition flaps have been proposed as an intraoperative modification to reduce lymphocele formation. However, data from randomised controlled trials on this subject are not conclusive. In particular, data on long-term efficacy and complications are lacking. The PIANOFORTE trial was the first randomised controlled trial exploring this subject and showed a negative outcome regarding lymphocele reduction by performing a peritoneal interposition flap. In this long-term follow-up of the trial (median 43 months postoperatively), we could confirm the initial result that, while the interposition flap does not have a negative impact on complications or functionality, there is also no effect on lymphocele reduction in the long term. Additionally, these results confirm the possibility of lymphocele formation beyond the third postoperative month, which has to be borne in mind in the follow-up of these patients. The available randomised controlled trials (RCTs) assessing the influence of peritoneal interposition flaps (PIF) on the reduction of symptomatic lymphoceles (sLCs) post robot-assisted radical prostatectomy (RARP) do not constitute a sufficient follow-up (FU) to assess the long-term effects. The PIANOFORTE trial was the first of these RCTs, showing no sLC reduction at the 3-month FU. Therefore, all 232 patients from the PIANOFORTE trial were invited for long-term FU. One hundred seventy-six patients (76%) presented themselves for FU and constituted the study group (SG). The median FU duration was 43 months. No significant differences in group allocation or LC endpoints at 90 days were observed between SG patients and patients not presenting themselves for the FU. During the FU period, four patients (2.3%) in the SG developed sLCs, and six patients (3.4%) developed asymptomatic lymphoceles (aLCs), which persisted in five patients (2.9%). There were no significant differences between PIF and non-PIF regarding sLC/aLC formation or persistence, newly developed complications, stress urinary incontinence or biochemical/clinical tumour recurrence. Therefore, this long-term FU confirms the primary outcomes of the PIANOFORTE trial that, while PIF does not impact complications or functionality, it does not reduce sLC/aLC rates. Furthermore, it shows the potential occurrence of LC after the third postoperative month. [ABSTRACT FROM AUTHOR]

Simple Summary: Lactococcus lactis subsp. cremoris C60, a probiotic lactic acid bacteria (LAB) strain, induces immunomodulation in myeloid cells, including macrophages. C60 was reported to suppress murine melanoma in our previous study, while the effect of this strain on macrophage anti-tumor activity is still uncharacterized. Here, we report that C60 enhances macrophage function by altering metabolic preference to glycolysis, allowing the cell to produce more adenosine triphosphate (ATP) and maintain an inflammatory status. Intratumor (IT) macrophages in C60-administered mice increase glycolysis rather than fatty acid oxidation (FAO) in their metabolism, which enables the cells to generate sufficient energy resources to increase their immune activity, including antigen-dependent CD8+ T cell activation in a murine melanoma model. This is the first report demonstrating that probiotic LAB assists macrophage function in anti-tumor immunity, providing a novel possibility for LAB adaptation in maintaining our health. Lactococcus lactis subsp. cremoris C60 is a probiotic strain of lactic acid bacteria (LAB) which induces various immune modifications in myeloid lineage cells. These modifications subsequently regulate T cell function, resulting in enhanced immunity both locally and systemically. Here, we report that C60 suppresses tumor growth by enhancing macrophage function via metabolic alterations, thereby increasing adenosine triphosphate (ATP) production in a murine melanoma model. Intragastric (i.g.) administration of C60 significantly reduced tumor volume compared to saline administration in mice. The anti-tumor function of intratumor (IT) macrophage was upregulated in mice administered with C60, as evidenced by an increased inflammatory phenotype (M1) rather than an anti-inflammatory/reparative (M2) phenotype, along with enhanced antigen-presenting ability, resulting in increased tumor antigen-specific CD8+ T cells. Through this functional modification, we identified that C60 establishes a glycolysis-dominant metabolism, rather than fatty acid oxidation (FAO), in IT macrophages, leading to increased intracellular ATP levels. To address the question of why orally supplemented C60 exhibits functions in distal places, we found a possibility that bacterial cell wall components, which could be distributed throughout the body from the gut, may induce stimulatory signals in peripheral macrophages via Toll-like receptors (TLRs) signaling activation. Thus, C60 strengthens macrophage anti-tumor immunity by promoting a predominant metabolic shift towards glycolysis upon TLR-mediated stimulation, thereby increasing substantial energy production. [ABSTRACT FROM AUTHOR]

Simple Summary: This is the first study to examine the impact of specialized community-based outpatient physical and occupational therapy on the health-related quality of life of cancer survivors with various cancers. Survivors who completed PT/OT reported significant improvements in physical and mental health, physical function, and social participation. Although more research is needed, these findings suggest cancer rehabilitation is an important strategy to meet HRQOL needs and lends support for inclusion as a standard of care. Compared to adults without cancer, cancer survivors report poorer health-related quality of life (HRQOL), which is associated with negative treatment outcomes and increased healthcare use. Cancer-specialized physical and occupational therapy (PT/OT) could optimize HRQOL; however, the impact among survivors with non-breast malignancies is unknown. This retrospective (2020–2022), observational, study of medical record data of 12 cancer types, examined pre/post-HRQOL among cancer survivors who completed PT/OT. PROMIS® HRQOL measures: Global Health (physical [GPH] and mental [GMH]), Physical Function (PF), and Ability to Participate in Social Roles and Activities (SRA) were evaluated using linear mixed effect models by cancer type, then compared to the minimal important change (MIC, 2 points). Survivors were 65.44 ± 12.84 years old (range: 19–91), male (54%), with a median of 12 visits. Improvements in GPH were significant (p < 0.05) for all cancer types and all achieved MIC. Improvements in GMH were significant for 11/12 cancer types and 8/12 achieved MIC. Improvements in PF were significant for all cancer types and all achieved the MIC. Improvements in SRA were significant for all cancer types and all groups achieved the MIC. We observed statistically and clinically significant improvements in HRQOL domains for each of the 12 cancer types evaluated. [ABSTRACT FROM AUTHOR]

Simple Summary: The relationship between head and neck cancer and heart attack is a complex area of medical research that has potential implications for patient care and outcomes. This study aimed to assess the risk of developing heart disease attributable to head and neck cancer. In this study, we examined the association between head and neck cancer and the risk of heart attack using a database of 1,025,340 South Korean patients. There were no associations between the development of a heart attack in head and neck cancer survivors who did not receive radiation or chemotherapy. Our results consistently indicated a negligible long-term increase in the risk of developing a heart attack after a head and neck cancer diagnosis. Enhanced screening protocols for cancer detection have increased survival in patients with head and neck cancer (HNC), which highlights the need to address the sequelae of therapy-induced cardiovascular complications. This study was conducted to assess the incidence and risk of acute myocardial infarction (AMI) in patients with HNC who have not undergone radiation or chemotherapy using a comprehensive, population-based cohort dataset. A total of 2976 individuals without cancer and 744 individuals with HNC were matched using the propensity score method. The findings indicated that the occurrence rates of AMI were comparable between the HNC (2.19) and non-cancer groups (2.39). Cox regression analysis did not demonstrate a significant increase in the risk of AMI in patients with HNC (hazard ratio: 0.93, 95% confidence interval: 0.50–1.73). No increased risk of AMI was observed in the HNC group compared to the non-cancer group, regardless of the time since the HNC diagnosis. Subgroup analyses showed no notable differences in the AMI risk between the groups when considering sex, age, comorbidities, and cancer type. This study showed that patients with HNC who have not been treated with radiation or chemotherapy did not exhibit an increased incidence or risk of AMI compared to individuals without cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Catheter-assisted ablations have shown significant improvements in the outcomes of percutaneous thermal ablation for liver cancer. A novel approach within this category is the Hepatic Arteriography and C-Arm CT-Guided Ablation (HepACAGA) technique, which integrates C-arm CT hepatic arteriography with C-arm guided navigation. This cohort study aimed to assess the effectiveness and safety of the HepACAGA technique compared to conventional ultrasound/CT-guided thermal ablation in treating hepatocellular carcinoma and colorectal liver metastasis. A total of 68 patients with 120 tumors undergoing HepACAGA and 53 patients with 78 tumors undergoing conventional ablation were included. The HepACAGA technique demonstrated superior outcomes: lower rates of local tumor recurrence, longer local tumor recurrence-free survival, and fewer procedure-related complications. These findings suggest that HepACAGA is a safer and more effective ablation technique in liver cancer treatment compared to conventional ablation methods. Purpose: Hepatic Arteriography and C-Arm CT-Guided Ablation of liver tumors (HepACAGA) is a novel technique, combining hepatic–arterial contrast injection with C-arm CT-guided navigation. This study compared the outcomes of the HepACAGA technique with patients treated with conventional ultrasound (US) and/or CT-guided ablation. Materials and Methods: In this retrospective cohort study, all consecutive patients with hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM) treated with conventional US-/CT-guided ablation between 1 January 2015, and 31 December 2020, and patients treated with HepACAGA between 1 January 2021, and 31 October 2023, were included. The primary outcome was local tumor recurrence-free survival (LTRFS). Secondary outcomes included the local tumor recurrence (LTR) rate and complication rate. Results: 68 patients (120 tumors) were included in the HepACAGA cohort and 53 patients (78 tumors) were included in the conventional cohort. In both cohorts, HCC was the predominant tumor type (63% and 73%, respectively). In the HepACAGA cohort, all patients received microwave ablation. Radiofrequency ablation was the main ablation technique in the conventional group (78%). LTRFS was significantly longer for patients treated with the HepACAGA technique (p = 0.015). Both LTR and the complication rate were significantly lower in the HepACAGA cohort compared to the conventional cohort (LTR 5% vs. 26%, respectively; p < 0.001) (complication rate 4% vs. 15%, respectively; p = 0.041). Conclusions: In this study, the HepACAGA technique was safer and more effective than conventional ablation for HCC and CRLM, resulting in lower rates of local tumor recurrence, longer local tumor recurrence-free survival and fewer procedure-related complications. [ABSTRACT FROM AUTHOR]

Simple Summary: Bone marrow (myelo-) fibrosis in myeloproliferative neoplasms is associated with poor prognosis and treatment failure emphasizing the importance of investigating novel treatment approaches outside the JAK pathway. This study investigates the role of neuropilin 2 (NRP2) in myelofibrosis and bone formation, identifies the type of stromal cells expressing and upregulating NRP2 and outcomes when NRP2 is lost. Our results suggest that NRP2 is an interesting molecular druggable target in myeloproliferative neoplasm. Bone marrow fibrosis in myeloproliferative neoplasm (MPN), myelodysplastic syndromes (MDS), MPN/MDS overlap syndromes and acute myeloid leukemia (AML) is associated with poor prognosis and early treatment failure. Myelofibrosis (MF) is accompanied by reprogramming of multipotent bone marrow mesenchymal stromal cells (MSC) into osteoid and fiber-producing stromal cells. We demonstrate NRP2 and osteolineage marker NCAM1 (neural cell adhesion molecule 1) expression within the endosteal niche in normal bone marrow and aberrantly in MPN, MDS MPN/MDS overlap syndromes and AML (n = 99), as assessed by immunohistochemistry. Increased and diffuse expression in mesenchymal stromal cells and osteoblasts correlates with high MF grade in MPN (p < 0.05 for NRP2 and NCAM1). Single cell RNA sequencing (scRNAseq) re-analysis demonstrated NRP2 expression in endothelial cells and partial co-expression of NRP2 and NCAM1 in normal MSC and osteoblasts. Potential ligands included transforming growth factor β1 (TGFB1) from osteoblasts and megakaryocytes. Murine ThPO and JAK2V617F myelofibrosis models showed co-expression of Nrp2 and Ncam1 in osteolineage cells, while fibrosis-promoting MSC only express Nrp2. In vitro experiments with MC3T3-E1 pre-osteoblasts and analysis of Nrp2−/− mouse femurs suggest that Nrp2 is functionally involved in osteogenesis. In summary, NRP2 represents a potential novel druggable target in patients with myelofibrosis. [ABSTRACT FROM AUTHOR]

Simple Summary: High-dose-rate (HDR) MRI-Assisted Radiosurgery (MARS) is an advanced form of brachytherapy or interventional radiotherapy involving the use of a remote after-loading system to transport an encapsulated radioisotope source to within or near a tumor with MRI precision. An HDR MARS can be used for treating both primary and recurrent prostate cancer with fewer treatment-related toxicities and comparable survival rates. Image-guided HDR brachytherapy has been linked with better local tumor control and overall survival. Magnetic resonance imaging (MRI) is more effective than computed tomography (CT) and ultrasonography in distinguishing the boundaries of a tumor versus the surrounding normal tissues. However, localizing the applicator and source is more challenging with MRI because conventional fiducial markers are not positively visualized on MRI. The aim of our study was to investigate the MRI signal intensities and characteristics of a newly developed positive-contrast MRI line marker (C4:S) for HDR MARS. We found that C4:S MRI line markers were positively visualized on both T1- and T2-weighted MRI sequences. Our findings indicate the value of C4:S line markers for HDR MARS. Magnetic resonance imaging (MRI) can facilitate accurate organ delineation and optimal dose distributions in high-dose-rate (HDR) MRI-Assisted Radiosurgery (MARS). Its use for this purpose has been limited by the lack of positive-contrast MRI markers that can clearly delineate the lumen of the HDR applicator and precisely show the path of the HDR source on T1- and T2-weighted MRI sequences. We investigated a novel MRI positive-contrast HDR brachytherapy or interventional radiotherapy line marker, C4:S, consisting of C4 (visible on T1-weighted images) complexed with saline. Longitudinal relaxation time (T1) and transverse relaxation time (T2) for C4:S were measured on a 1.5 T MRI scanner. High-density polyethylene (HDPE) tubing filled with C4:S as an HDR brachytherapy line marker was tested for visibility on T1- and T2-weighted MRI sequences in a tissue-equivalent female ultrasound training pelvis phantom. Relaxivity measurements indicated that C4:S solution had good T1-weighted contrast (relative to oil [fat] signal intensity) and good T2-weighted contrast (relative to water signal intensity) at both room temperature (relaxivity ratio > 1; r2/r1 = 1.43) and body temperature (relaxivity ratio > 1; r2/r1 = 1.38). These measurements were verified by the positive visualization of the C4:S (C4/saline 50:50) HDPE tube HDR brachytherapy line marker on both T1- and T2-weighted MRI sequences. Orientation did not affect the relaxivity of the C4:S contrast solution. C4:S encapsulated in HDPE tubing can be visualized as a positive line marker on both T1- and T2-weighted MRI sequences. MRI-guided HDR planning may be possible with these novel line markers for HDR MARS for several types of cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the increased risk of developing renal cell carcinoma (RCC) in patients with advanced chronic kidney disease (ACKD), little is known about the patient clinical characteristics and genetic mutations found in these RCC tumors. Using a multi-institutional research network, this study compiled clinical records and somatic tumor whole exome sequencing data of 296 adult patients with RCC, 61 of whom had ACKD. Patients with RCC and ACKD were more likely to be male, present with earlier stage RCC at diagnosis, and have lower rates of BAP1 mutations. Median overall survival was not reached in either group over a median follow-up of 31.3 months. These findings suggest RCC in patients with ACKD develops via a BAP1-independent mutational driver and further support BAP1 loss as a marker of disease aggressiveness. Background: Patients with advanced chronic kidney disease (ACKD) are at an increased risk of developing renal cell carcinoma (RCC), but molecular alterations in RCC specimens arising from ACKD and overall survival (OS) in affected patients are not well defined. Patients and Methods: Using the Oncology Research Information Exchange Network (ORIEN) Total Cancer Care® protocol, 296 consented adult patients with RCC and somatic tumor whole exome sequencing were included. Patients with ACKD were defined as those with serum creatinine ≥1.5 mg/dL prior to RCC diagnosis. Results: Of 296 patients with RCC, 61 met the criteria for ACKD. The most common somatic mutations in the overall cohort were in VHL (126, 42.6%), PBRM1 (102, 34.5%), and SETD2 (54, 18.2%). BAP1 had a decreased mutational frequency in RCC specimens from patients without ACKD as compared to those with ACKD (10.6% versus 1.6%), but this was not statistically significant in univariable (OR 0.14, p = 0.056) or multivariable (OR 0.15, p = 0.067) analysis. Median OS was not reached in either cohort. Conclusions: Using the clinicogenomic ORIEN database, our study found lower rates of BAP1 mutations in RCC specimens from patients with ACKD, which may reflect a BAP1-independent mutational driver of RCC in patients with ACKD. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation-associated sarcomas pose a significant clinical challenge due to their complexity, aggressiveness, and poor prognosis. Our retrospective study is one of the largest descriptions of radiation-associated sarcomas, aiming to shed light on their clinicopathologic characteristics and highlight treatment approaches. Our research found a significant association between high radiation-associated sarcoma histologic grade and inferior clinical outcomes. We also found that localized radiation-associated sarcoma patients who underwent margin-negative resections lived significantly longer than their counterparts. Our analysis thus confirms the paramount role of tumor grade and the central importance of margin-negative oncologic resection in determining clinical outcomes for radiation-associated sarcomas. Radiation-associated sarcomas (RASs) are rare tumors with limited contemporary data to inform prognostication and management. We sought to identify the clinical presentation, patterns of care, and prognostic factors of RASs. RAS patients treated at a single institution from 2015 to 2021 were retrospectively reviewed for clinicopathologic variables, treatment strategies, and outcomes. Thirty-eight patients were identified with a median follow-up of 30.5 months. The median age at RAS diagnosis was 68.4 years (27.9–85.4), with a median latency from index radiotherapy (RT) of 9.1 years (3.7–46.3). RAS histologies included angiosarcoma (26%), undifferentiated pleomorphic sarcoma (21%), and osteosarcoma (18%). Most were high-grade (76%). Genomic profiling revealed low tumor mutational burden, frequent inactivating TP53 mutations (44%), CDKN2A deletions (26%), and MYC amplifications (22%), particularly in breast angiosarcomas. Of 38 patients, 33 presented with localized disease, 26 of whom were treated with curative intent. Overall, the median progression-free survival (PFS) was 9.5 months (1.4–34.7), and the overall survival (OS) was 11.1 months (0.6–31.6). Patients with localized vs. metastatic RASs had a longer PFS (HR, 3.0 [1.1–8.5]; p = 0.03) and OS (HR, 3.0 [1.04–8.68]; p = 0.03). Among localized RAS patients, high grade was associated with shorter OS (HR, 4.6 [1.04–20.30]; p = 0.03) and resection with longer OS (mean 58.8 vs. 6.1 months, HR, 0.1 [0.03–0.28]; p < 0.001). Among patients undergoing resection, negative margins were associated with improved OS (mean 71.0 vs. 15.5 months, HR, 5.1 [1.4–18.2]; p = 0.006). Patients with localized disease, particularly those undergoing R0 resection, demonstrated significantly better outcomes. Novel strategies are urgently needed to improve treatment outcomes in this challenging group of diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: This study is an analysis of the metastatic pattern of distant metastases in patients with mesothelioma screened for multimodal treatment and during follow-up. A precise staging of patients undergoing multimodal treatment is mandatory. Distant metastases are more frequent in mesothelioma patients than previously thought. This implies that extensive staging is needed for patients selected for multimodal treatment, including brain imaging and 18FDG-PET CT. Pleural mesothelioma (PM) is a very aggressive malignancy with a poor prognosis. Most patients receive systemic treatment only; however, some patients may benefit from multimodality treatment. A precise staging of patients undergoing multimodal treatment is mandatory. We investigated the pattern of metastasis in a cohort of patients screened for multimodal treatment to define the extent of staging examinations. Additionally, we investigated the occurrence of metastasis during follow-up. We investigated a single-center experience of 545 patients newly diagnosed and/or treated with PM between the years 2010 and 2022. Patients who were treated naïvely and had a whole set of imaging of the brain were included and further analyzed. A total of 54% of all patients with cerebral imaging had an available 18FDG-PET CT scan. We also recorded metastasis during treatment follow-up. There were 110 patients who had a whole set of imaging (CT = 89% and MRI = 11%) of the brain, and 54% of all patients with cerebral imaging had an available 18FDG-PET CT scan. We identified four patients with cerebral metastasis at the time of first diagnosis, which means that 5.4% of the cohort had cerebral metastasis and 13.3% of all patients in the subgroup with complete data of 18FDG-PET CT had distant non-cerebral metastasis. During the longitudinal follow-up, we found 11 patients with newly diagnosed metastases after a median time of 1.6 years (range: 2 months to 3.3 years) after first diagnosis without metastases. Distant metastases are more frequent in mesothelioma patients than previously thought. This implies that extensive staging is needed for patients selected for multimodal treatment, including brain imaging and 18FDG-PET CT. [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: This study investigated whether using virtual reality (VR) could help reduce anxiety in women undergoing gynecological cancer surgery. Participants were split into two groups: one receiving VR therapy alongside usual care and the other receiving only usual care. Results showed that VR significantly decreased anxiety levels before surgery compared to the control group. This suggests that VR could be a valuable tool in preparing patients for surgery, potentially improving their experience and outcomes. Further research is needed to explore VR's benefits in other types of surgery and its long-term effects on patient recovery. Perioperative anxiety is common among patients undergoing surgery, potentially leading to negative outcomes. Immersive virtual reality (VR) has shown promise in reducing anxiety in various clinical settings. This study aimed to evaluate the effectiveness of VR in reducing perioperative anxiety in patients undergoing gynecological oncology surgery and was conducted as a single-center, double-arm, single-blinded randomized controlled trial at the Gold Coast University Hospital, Queensland, Australia. Participants were randomized into the VR intervention + care as usual (CAU) group (n = 39) and the CAU group (n = 41). Anxiety scores were assessed using a six-tier visual facial anxiety scale at baseline, after the intervention/CAU on the same day, and, several days up to weeks later, immediately before surgery. There was no significant difference in baseline anxiety scores, type of operation, or suspected cancer between the two groups. The VR intervention significantly reduced anxiety scores from baseline to preoperative assessment (p < 0.001). The median anxiety score in the VR intervention group decreased from 3 (interquartile range 2 to 5) at baseline to 2 (2 to 3) prior to surgery, while the control group's scores were 4 (2 to 5) and 4 (3 to 5), respectively. Multivariate analysis showed that group assignment was the sole outcome predictor, not age, type of procedure, or the time elapsed until surgery. Thus, VR exposure was effective in reducing perioperative anxiety in patients undergoing gynecological oncology surgery. The use of VR as a preparation tool may improve patient experience and contribute to better surgical outcomes, warranting further research into exploring the potential benefits of VR in other surgical specialties and its long-term impact on patient recovery. [ABSTRACT FROM AUTHOR]

Simple Summary: One of the most prevalent malignancies across the world is female breast cancer, accounting for 25% of all diagnosed cancers. Physical exercise has been recognized as an important strategy for prevention and treatment during the cancer continuum. Home-based exercise programs can produce greater adherence rates than in-person interventions. However, the majority of home-based programs are carried out employing practical guides, brochures or electronic materials without supervision, which can increase the risk of injury and adverse effects. The aim of this study was to analyze the effect of a synchronous-supervised online home-based exercise program during 24 weeks on body composition, physical fitness and adherence compared to an exercise recommendation group without supervision with patients undergoing breast cancer treatment. We confirmed that supervised home-based exercise interventions can be an interesting strategy to improve physical fitness and adherence rates in breast cancer patients undergoing treatment. The purpose of the present study was to analyze the effect of a synchronous-supervised online home-based exercise program (HBG) during 24 weeks on body composition, physical fitness and adherence compared to an exercise recommendation group (ERG) without supervision with patients undergoing breast cancer treatment. Fifty-nine female breast cancer patients (31 in HBG and 28 in the ERG) undergoing cancer treatments participated in the present randomized clinical trial. The exercise program consisted of a 60 min combined resistance and aerobic supervised exercise session (6–8 points on Borg Scale CR-10, moderate intensity), twice a week during 24 weeks. The exercise recommendation group only received general recommendations to comply with the current ACSM guidelines. Body composition and physical fitness were assessed at baseline, 12 weeks and 24 weeks of the program. Adherence to the intervention was measured according to the minutes of exercise completed per session during each week. A general linear model of two-way repeated measures showed significant improvements (p < 0.05) in physical fitness that were observed in the home-based exercise group at the baseline, 12-week and 24-week assessments compared to the exercise recommendation group. Adherence was also higher in the home-based exercise group. However, no changes (p > 0.05) in body composition between groups and moments were observed. In this sense, supervised home-based exercise interventions can be an interesting strategy to improve physical fitness and adherence rates in breast cancer patients undergoing treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: High-resolution anoscopy (HRA) is crucial for spotting and treating early signs of anal cancer. The researchers created an artificial intelligence (AI) system to analyze HRA images and identify high-grade and low-grade lesions accurately. They trained a computer program with thousands of images, achieving a remarkable accuracy of 94.6%. The AI system proved effective across different examination methods, such as using acetic acid or lugol iodine, and even after treatment. This advancement could improve the early detection of anal cancer precursors, potentially saving lives. High-resolution anoscopy (HRA) plays a central role in the detection and treatment of precursors of anal squamous cell carcinoma (ASCC). Artificial intelligence (AI) algorithms have shown high levels of efficiency in detecting and differentiating HSIL from low-grade squamous intraepithelial lesions (LSIL) in HRA images. Our aim was to develop a deep learning system for the automatic detection and differentiation of HSIL versus LSIL using HRA images from both conventional and digital proctoscopes. A convolutional neural network (CNN) was developed based on 151 HRA exams performed at two volume centers using conventional and digital HRA systems. A total of 57,822 images were included, 28,874 images containing HSIL and 28,948 LSIL. Partial subanalyses were performed to evaluate the performance of the CNN in the subset of images acetic acid and lugol iodine staining and after treatment of the anal canal. The overall accuracy of the CNN in distinguishing HSIL from LSIL during the testing stage was 94.6%. The algorithm had an overall sensitivity and specificity of 93.6% and 95.7%, respectively (AUC 0.97). For staining with acetic acid, HSIL was differentiated from LSIL with an overall accuracy of 96.4%, while for lugol and after therapeutic manipulation, these values were 96.6% and 99.3%, respectively. The introduction of AI algorithms to HRA may enhance the early diagnosis of ASCC precursors, and this system was shown to perform adequately across conventional and digital HRA interfaces. [ABSTRACT FROM AUTHOR]

Simple Summary: The selection of radiation dose/fractionation schemes for limited-stage small cell lung cancer (LS-SCLC) is highly controversial. It mainly involves the impact of total biologically effective dose, overall treatment time, and fractionation dose on survival and toxicity. This article comprehensively analyzes current relevant research and discusses the advantages and disadvantages of conventional-dose/fractionation radiotherapy (ConvTRT), hyperfractionated radiotherapy (HyperTRT), hypofractionated radiotherapy (HypoTRT), and stereotactic body radiotherapy (SBRT), in order to find the most suitable dose fractionation scheme and provide reference for clinical practice. Regardless of the radiotherapy modality, controlling the radiotherapy time to around 3 weeks is beneficial for improving survival and local control rates while reducing toxicity reactions. ConvTRT with a high total prescription dose is not recommended, because a prolonged radiotherapy time may reduce the tumor control probability of some rapidly proliferating tumor cells. In balancing acute reactions, late reactions, and treatment outcomes (local control or overall survival), the advantages of HyperTRT over HypoTRT still exist. For the radical radiotherapy regimen recommended by current guidelines (45 Gy/30 fractions), we suggest moderately increasing the fractionation dose and total dose, which may further improve prognosis. To explore the most suitable dosage regimen for limited-stage small cell lung cancer (LS-SCLC) and provide references for clinical selection, strict inclusion criteria were applied, and studies were screened from Pubmed, Embase, and Web of Science. Subsequently, data on two-year overall survival rates and dosage regimens were collected, and scatter plots were constructed to provide a comprehensive perspective. The survival benefits of various dosage regimens were evaluated, and a linear quadratic equation was utilized to fit the relationship between the biologically effective dose (BED10) and the two-year overall survival rate. Among the five randomized controlled trials, the two-year overall survival rate of ConvTRT regimens with BED10 > 60 Gy (rough value) was only at or below the median of all ConvTRT regimens or all included study regimens, indicating that increasing the number and total dose of ConvTRT does not necessarily lead to better prognosis. In the exploration of HypoTRT regimens, there was a linear positive correlation between BED10 and the two-year overall survival rate (p < 0.0001), while the exploration of HyperTRT regimens was relatively limited, with the majority focused on the 45 Gy/30 F regimen. However, the current 45 Gy/30 F regimen is not sufficient to control LS-SCLC, resulting in a high local recurrence rate. High-dose ConvTRT regimens have long treatment durations and may induce tumor regrowth which may cause reduced efficacy. Under reasonable toxicity reactions, HyperTRT or HypoTRT with higher radiotherapy doses is recommended for treating LS-SCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: Pulmonary oncological issues are a significant public health concern, often complicated by the presence of other pulmonary conditions, which can complicate diagnosis, staging, and treatment decisions. To explore this complexity, we conducted a retrospective study at the Marius Nasta Institute of Pneumophthisiology in Bucharest, Romania, focusing on patients diagnosed with carcinoid and/or non-small-cell lung carcinoma and coexisting pathologies. Patients with both malignant and nonmalignant lesions shared similar demographic and exposure profiles with those presenting only malignant lesions. Synchronous coexisting lesions may complicate the diagnosis and staging of lung cancer. Pulmonary oncological pathologies are an important public health problem and the association with other pulmonary lesions may pose difficulties in diagnosis and staging or require different treatment options. To address this complexity, we conducted a retrospective observational study at the Marius Nasta Institute of Pneumophthisiology, Bucharest, Romania. Our study focused on patients admitted in 2019 with non-small-cell lung carcinoma and associated pulmonary lesions identified through surgical resection specimens. Among the 314 included patients, multiple pulmonary nodules were observed on macroscopic examination, with 12% (N = 37) exhibiting nonmalignant etiologies upon microscopic examination. These findings underscore the challenge of preoperative staging. Patients with coexisting nonmalignant lesions were similar in age, smoking habits, and professional or environmental exposure by comparison with those who presented only malignant lesions. The presentation of coexisting malignant and nonmalignant lesions may pose difficulties in diagnosing and staging pulmonary cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: We developed an attention-based whole slide image (WSI)-level classification deep learning model employing surgically and endoscopically resected specimens to predict LNM in T1 CRC. Our AI model with H&E-stained WSIs and without annotations showed good performance power with the validation of an independent cohort in a single center. The area under the curve of our model was 0.781–0.824, higher than that of previous artificial intelligence (AI) studies with only WSIs. Our AI model, which showed the highest sensitivity (92.9%), reduced unnecessary additional surgery by 14.2% more than using the current JSCCR guidelines (68.3% vs. 82.5%). This revealed the feasibility of using an AI model with only H&E-stained WSIs to predict LNM in T1 CRC. According to the current guidelines, additional surgery is performed for endoscopically resected specimens of early colorectal cancer (CRC) with a high risk of lymph node metastasis (LNM). However, the rate of LNM is 2.1–25.0% in cases treated endoscopically followed by surgery, indicating a high rate of unnecessary surgeries. Therefore, this study aimed to develop an artificial intelligence (AI) model using H&E-stained whole slide images (WSIs) without handcrafted features employing surgically and endoscopically resected specimens to predict LNM in T1 CRC. To validate with an independent cohort, we developed a model with four versions comprising various combinations of training and test sets using H&E-stained WSIs from endoscopically (400 patients) and surgically resected specimens (881 patients): Version 1, Train and Test: surgical specimens; Version 2, Train and Test: endoscopic and surgically resected specimens; Version 3, Train: endoscopic and surgical specimens and Test: surgical specimens; Version 4, Train: endoscopic and surgical specimens and Test: endoscopic specimens. The area under the curve (AUC) of the receiver operating characteristic curve was used to determine the accuracy of the AI model for predicting LNM with a 5-fold cross-validation in the training set. Our AI model with H&E-stained WSIs and without annotations showed good performance power with the validation of an independent cohort in a single center. The AUC of our model was 0.758–0.830 in the training set and 0.781–0.824 in the test set, higher than that of previous AI studies with only WSI. Moreover, the AI model with Version 4, which showed the highest sensitivity (92.9%), reduced unnecessary additional surgery by 14.2% more than using the current guidelines (68.3% vs. 82.5%). This revealed the feasibility of using an AI model with only H&E-stained WSIs to predict LNM in T1 CRC. [ABSTRACT FROM AUTHOR]

Simple Summary: In order to grow, tumors need nutrients and oxygen, which are supplied by new blood vessels that are often abnormal and leaky. The development of these blood vessels is driven by proteins called growth factors, which bind to receptor proteins on other cells. We show for the first time that an antibody against a vascular growth factor called VEGF-B, when used to treat mice with tumors, reduces the amount of abnormal tumor blood vessels, and inhibits tumor growth, as well as improving the response to chemotherapy. These results suggest that targeting VEGF-B could be a potential approach for anti-cancer therapy, particularly in combination with chemotherapy. The vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are key regulators of blood vessel formation, including in tumors, where their deregulated function can promote the production of aberrant, leaky blood vessels, supporting tumor development. Here we investigated the VEGFR1 ligand VEGF-B, which we demonstrate to be expressed in tumor cells and in tumor stroma and vasculature across a range of tumor types. We examined the anti-VEGF-B-specific monoclonal antibody 2H10 in preclinical xenograft models of breast and colorectal cancer, in comparison with the anti-VEGF-A antibody bevacizumab. Similar to bevacizumab, 2H10 therapy was associated with changes in tumor blood vessels and intra-tumoral diffusion consistent with normalization of the tumor vasculature. Accordingly, treatment resulted in partial inhibition of tumor growth, and significantly improved the response to chemotherapy. Our studies indicate the importance of VEGF-B in tumor growth, and the potential of specific anti-VEGF-B treatment to inhibit tumor development, alone or in combination with established chemotherapies. [ABSTRACT FROM AUTHOR]

Simple Summary: This study systematically reviewed case reports to identify rare adverse events in small cell lung cancer (SCLC) patients treated with immune checkpoint inhibitors (ICIs). A literature search, limited to reports published up to 31 December 2023, yielded 24 studies involving various ICIs, including atezolizumab, durvalumab, and nivolumab, either as monotherapy or in combination treatments. The review documented adverse events predominantly affecting the respiratory system, along with neurological, endocrinological, and gastroenterological systems. A total of 87.5% of cases showed symptom improvement, although some reports indicated severe outcomes, including death or persistent sequelae. The findings highlight the unpredictability of ICIs' adverse effects and emphasize the importance of developing reliable biomarkers and multidisciplinary strategies to enhance patient management and safety in immunotherapy. Background: This study aimed to systematically review case reports documenting rare adverse events in patients with small cell lung cancer (SCLC) following the administration of immune checkpoint inhibitors (ICIs). Methods: A systematic literature review was conducted to identify case reports detailing previously unreported adverse drug reactions to ICIs in patients with SCLC. The scope of the literature reviewed was restricted to case studies on SCLC published up to 31 December 2023. Results: We analyzed twenty-four studies on ICI use for patients with SCLC. There were six reports on atezolizumab, four on durvalumab, and three on adverse events from monotherapy with nivolumab. Reports involving combination treatments were the most frequent, with a total of six, predominantly involving using nivolumab in combination with ipilimumab. Additionally, there was one report each on using pembrolizumab, nofazinilimab, sintilimab, tislelizumab, and toripalimab. We collected detailed information on the clinical course, including patient and disease characteristics, symptoms, treatment for each adverse event, and recovery status. Among the patients included in the case reports, 21 out of 24 (87.5%) had extensive-stage SCLC when initiating ICI therapy, with only 1 patient diagnosed with limited-stage SCLC. Respiratory system adverse events were most common, with seven cases, followed by neurological, endocrinological, and gastroenterological events. Three case reports documented adverse events across multiple systems in a single patient. In most cases, patients showed symptom improvement; however, four studies reported cases where patients either expired without symptom improvement or experienced sequelae. Conclusions: Efforts to develop reliable biomarkers for predicting irAEs continue, with ongoing research to enhance predictive precision. Immunotherapy presents diverse and unpredictable adverse events, underscoring the need for advanced diagnostic tools and a multidisciplinary approach to improve patient management. [ABSTRACT FROM AUTHOR]

Simple Summary: Ensuring precise needle placement during biopsy procedures is essential for both successful outcomes and minimizing patient risk. Our study presents a new mixed reality system that helps doctors accurately navigate needles to their intended targets without needing physical markers. By using advanced imaging and computer vision techniques, the system overlays anatomical data directly onto the patient, guiding the needle along a pre-planned path. We tested this system in various ways, including its accuracy and efficiency in needle placement. Our findings showcased a significant improvement, with a reduction in number of punctures needed to reach the target location. The test was successfully completed on the first attempt in 70% of cases, as opposed to only 20% without the system. Additionally, there was a 53% reduction in procedure time, validating the effectiveness of the system. Exact biopsy planning and careful execution of needle injection is crucial to ensure successful procedure completion as initially intended while minimizing the risk of complications. This study introduces a solution aimed at helping the operator navigate to precisely position the needle in a previously planned trajectory utilizing a mixed reality headset. A markerless needle tracking method was developed by integrating deep learning and deterministic computer vision techniques. The system is based on superimposing imaging data onto the patient's body in order to directly perceive the anatomy and determine a path from the selected injection site to the target location. Four types of tests were conducted to assess the system's performance: measuring the accuracy of needle pose estimation, determining the distance between injection sites and designated targets, evaluating the efficiency of material collection, and comparing procedure time and number of punctures required with and without the system. These tests, involving both phantoms and physician participation in the latter two, demonstrated the accuracy and usability of the proposed solution. The results showcased a significant improvement, with a reduction in number of punctures needed to reach the target location. The test was successfully completed on the first attempt in 70% of cases, as opposed to only 20% without the system. Additionally, there was a 53% reduction in procedure time, validating the effectiveness of the system. [ABSTRACT FROM AUTHOR]

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

Simple Summary: Invasive lobular carcinoma represents a distinct histological type of breast cancer, characterised by morphological, genetic, and behavioural differences from other types. However, the behaviour of invasive lobular carcinomas is not uniform, and some tumours show poor outcome. This may attribute to the presence of aggressive variants. Therefore, we performed detailed investigation of a large series of cases to characterise this aggressive subtype of invasive lobular carcinoma. This subtype, which includes the pleomorphic and high-grade solid variants accounts for 14% of lobular carcinomas. It showed associations with unfavourable prognostic features, poor patient outcomes, and poor response to therapy when compared to classic lobular carcinoma and invasive ductal carcinoma of no special type. Background: Invasive lobular carcinoma (ILC), the most common special type of breast cancer (BC), has unique clinical behaviour and is different from invasive ductal carcinoma of no special type (IDC-NST). However, ILC further comprises a diverse group of tumours with distinct features. This study aims to examine the clinicopathological and prognostic features of different variants of ILC, with a particular focus on characterising aggressive subtypes. Methods: A large (n = 7140) well-characterised and histologically reviewed BC cohort with treatment and long-term follow-up data was investigated. The cohort was classified based on the WHO classification of tumours into main histological subtypes, including ILC and IDC-NST. ILCs were further classified into variants. Clinicopathological parameters and patient outcomes in terms of BC-specific survival (BCSS) and disease-free survival (DFS) were evaluated. Results: ILC constituted 11% of the cohort. The most common non-classic ILC variants were pleomorphic (pILC) and solid (sILC), constituting 19% of ILC. Compared to classic and related variants (alveolar, trabecular, papillary, and tubulolobular; cILC), pILC and sILC variants were associated with aggressive tumour characteristics. The histologic grade of ILC was an important prognostic variable. The survival patterns identified an aggressive ILC subtype encompassing pILC and high-grade sILC. These tumours, which comprised 14% of the cases, were associated with clinicopathological characteristics of poor prognosis and had high BC-specific death and recurrence rates compared not only to cILC (p < 0.001) but also to IDC-NST (p = 0.02) patients. Contrasting this, cILC patients had significantly longer BCSS and DFS than IDC-NST patients in the first 10 to 15 years of follow-up. Adjuvant chemotherapy did not improve the outcome of patients with aggressive ILC subtypes. Conclusions: pILC and high-grade sILC variants comprise an aggressive ILC subtype associated with poor prognostic characteristics and a poor response to chemotherapy. These results warrant confirmation in randomised clinical trials. [ABSTRACT FROM AUTHOR]

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

Simple Summary: Melanoma, the deadliest skin cancer, is a focus of research worldwide. This malignancy has been demonstrated to evade the immune system through several escape mechanisms. Among these, melanoma-related Dendritic Cells (DCs) alterations, particularly within the Sentinel Lymph Node (SLN), seem to play a key role. In SLNs, melanoma-related factors create a tumor microenvironment capable of impairing the immune response, inducing tolerance to tumor antigens and thus favoring SLN early metastases. The present literature review describes the interactions between Langerhans Cell (LC), a particular DC subset, and melanoma, suggesting a new potential therapeutic target. Background. Langerhans cells (LCs) are professional Dendritic Cells (DCs) involved in immunoregulatory functions. At the skin level, LCs are immature. In response to tissue injuries, they migrate to regional Lymph Nodes (LNs), reaching a full maturation state. Then, they become effective antigen-presenting cells (APCs) that induce anti-cancer responses. Notably, melanoma patients present several DC alterations in the Sentinel Lymph Node (SLN), where primary antitumoral immunity is generated. LCs are the most represented DCs subset in melanoma SLNs and are expected to play a key role in the anti-melanoma response. With this paper, we aim to review the current knowledge and future perspectives regarding LCs and melanoma. Methods. A systematic review was carried out according to the PRISMA statement using the PubMed (MEDLINE) library from January 2004 to January 2024, searching for original studies discussing LC in melanoma. Results. The final synthesis included 15 articles. Several papers revealed significant LCs–melanoma interactions. Conclusions. Melanoma immune escape mechanisms include SLN LC alterations, favoring LN metastasis arrival/homing and melanoma proliferation. The SLN LCs of melanoma patients are defective but not irreversibly, and their function may be restored by appropriate stimuli. Thus, LCs represent a promising target for future immunotherapeutic strategies and cancer vaccines. [ABSTRACT FROM AUTHOR]

Simple Summary: Treosulfan and melphalan (TreoMel)-based high-dose chemotherapy (HDCT) has been successfully used as a conditioning regimen in acute myeloid leukemia (AML) patients undergoing autologous stem cell transplantation (ASCT). However, despite intensive first-line induction treatment and upfront consolidation with HDCT and ASCT, AML relapse rates are still high, and further efforts are needed to improve patient outcomes. In this study, we investigated how increased doses of melphalan impact the safety of HDCT with TreoMel and patient outcomes. A total of 51 AML patients were included in the analysis: 31 (60.8%) received standard-dose treosulfan combined with melphalan 140 mg/m2 (TreoMel 140) and 20 (39.2%) received melphalan 200 mg/m2 (TreoMel 200). There were no statistically significant differences in relapse (0.45 vs. 0.30, p = 0.381) and mortality rates (0.42 vs. 0.15, p = 0.064) between the melphalan 140 mg/m2 and 200 mg/m2 cohorts, nor for PFS (HR: 0.81, 95% CI: 0.29–2.28, p = 0.70) or OS (HR: 0.70, 95% CI: 0.19–2.57, p = 0.59) for the TreoMel 140 vs. TreoMel 200 cohorts. The side effect profile was comparable between both patient groups. Our results show that a higher melphalan dose is well tolerated. No significant differences for patient outcomes could be observed, possibly due to the relatively small patient cohort and short follow-up. Longer follow-up and prospective randomized studies would be required to confirm the safety profile and clinical benefit. (1) Background: Treosulfan and melphalan (TreoMel)-based high-dose chemotherapy (HDCT) has shown promising safety and efficacy as a conditioning regimen for acute myeloid leukemia (AML) patients undergoing autologous stem cell transplantation (ASCT). However, despite intensive first-line induction treatment and upfront consolidation with HDCT and ASCT, AML relapse rates are still high, and further efforts are needed to improve patient outcomes. The aim of this study was to compare two melphalan dose schedules in regard to the safety of TreoMel HDCT and patient outcomes. (2) Methods: We retrospectively analyzed the safety and efficacy of two melphalan dose schedules combined with standard-dose treosulfan in AML patients undergoing HDCT and ASCT at the University Hospital of Bern, Switzerland, between August 2019 and August 2023. Patients received treosulfan 42 g/m2 combined with either melphalan 140 mg/m2 (TreoMel 140) or melphalan 200 mg/m2 (TreoMel 200). Co-primary endpoints were progression-free survival (PFS), overall survival (OS), as well as safety profile. (3) Results: We included a total of 51 AML patients: 31 (60.8%) received TreoMel 140 and 20 (39.2%) TreoMel 200. The patients' basal characteristics were comparable between both cohorts. No significant differences in the duration of hospitalization or the adverse event profile were identified. There were no statistically significant differences in relapse (0.45 vs. 0.30, p = 0.381) and mortality rates (0.42 vs. 0.15, p = 0.064) between the melphalan 140 mg/m2 and 200 mg/m2 cohorts, nor for PFS (HR: 0.81, 95% CI: 0.29–2.28, p = 0.70) or OS (HR: 0.70, 95% CI: 0.19–2.57, p = 0.59) for the TreoMel 140 vs. TreoMel 200 cohort. (4) Conclusions: A higher dose of melphalan (TreoMel 200) was well tolerated overall. No statistically significant differences for patient outcomes could be observed, possibly due to the relatively small patient cohort and the short follow-up. A longer follow-up and prospective randomized studies would be required to confirm the safety profile and clinical benefit. [ABSTRACT FROM AUTHOR]