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Simple Summary: Our findings confirm the role of developmental aspects in extracranial germ cell tumors (eGCTs). Strong associations between syndromes or congenital anomalies and eGCTs may hint at the need for research to identify potential causes and mechanisms. Strong effects were observed for Swyer and Currarino syndrome. The strengths of the associations emphasize the need for further elaboration on presently discussed pathophysiological mechanisms. For other suggested risk factors such as Klinefelter, Turner, and Down syndrome, the strength of risk appears to be substantially low and may be missed because of diagnostic bias for the first two or lack of power for the latter. A number of further syndromes were identified in single cases. Most of these pertain to girls. GCTs are developmental tumors and are likely to reflect ontogenetic and teratogenetic determinants. The objective of this study was to identify syndromes with or without congenital anomalies and non-syndromic defects as potential risk factors. Patients with extracranial GCTs (eGCTs) registered in MAKEI 96/MAHO 98 between 1996 and 2017 were included. According to Teilum's holistic concept, malignant and benign teratomas were registered. We used a case–control study design with Orphanet as a reference group for syndromic defects and the Mainz birth registry (EUROCAT) for congenital anomalies at birth. Co-occurring genetic syndromes and/or congenital anomalies were assessed accordingly. Odds ratios and 95% confidence intervals were calculated and p-values for Fisher's exact test with Bonferroni correction if needed. A strong association was confirmed for Swyer (OR 338.6, 95% CI 43.7–2623.6) and Currarino syndrome (OR 34.2, 95% CI 13.2–88.6). We additionally found 16 isolated cases of eGCT with a wide range of syndromes. However, these were not found to be significantly associated following Bonferroni correction. Most of these cases pertained to girls. Regarding non-syndromic defects, no association with eGCTs could be identified. In our study, we confirmed a strong association for Swyer and Currarino syndromes with additional congenital anomalies. [ABSTRACT FROM AUTHOR]

Simple Summary: Sodium–glucose cotransporter-2 inhibitors (SGLT2Is) have been reported to be associated with renal cell carcinoma (RCC) risk. However, the effect between individual SGLT2Is on RCC incidence in patients with type 2 diabetes (T2D) is unclear. In this study, we aimed to explore type disparity in the prescription of SGLT2Is on RCC risk. After a 5.5-year follow-up, SGLT2I use was associated with a significantly lower risk of incident RCC. Furthermore, significant disparity was observed in SGLT2I use, with lower rates observed in dapagliflozin and empagliflozin, in contrast to canagliflozin. (1) Background: Recently, sodium–glucose cotransporter-2 inhibitors (SGLT2Is) have been reported to significantly reduce renal cell carcinoma (RCC) risk. However, the effect between individual SGLT2Is on RCC incidence in patients with type 2 diabetes (T2D) or heart failure is unclear. We conducted an observational analysis to explore type disparity in the prescription of SGLT2Is on RCC risk. (2) Methods: A nationwide retrospective cohort study using the Health and Welfare Data Science Center database (2016–2021) was conducted. Patients aged ≥40 years who took SGLT2Is were designated as the SGLT2I group, whereas propensity score 1:1-matched randomly selected patients without SGLT2Is were assigned to the non-SGLT2I group. The primary outcome was the risk of incident RCC between individual SGLT2Is. Multiple Cox regression modeling was conducted to analyze the association between individual SGLT2I use and RCC risk. (3) Results: After a 5.5-year follow-up, SGLT2I use was associated with a significantly lower risk of incident RCC (hazard: 0.62; 95% confidence interval [CI]: 0.44–0.89). Compared with non-users and after adjusting for the index year, sex, age, comorbidities, concurrent medication, and the risk of developing RCC, the hazard ratios of dapagliflozin, canagliflozin, and empagliflozin were 0.66 (95% CI: 0.53–0.83), 0.84 (95% CI: 0.46–1.30), and 0.71 (95% CI: 0.56–0.90), respectively. (4) Conclusions: Our data show a type-based effect of SGLT2Is on RCC risk. The type-based effect of SGLT2Is should be further studied for better clinical management information and for reducing RCC incidence in patients with T2D. [ABSTRACT FROM AUTHOR]

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: Oral squamous cell carcinoma is a global health concern, particularly affecting the South Asian population. The South Asian community is among Canada's largest and most rapidly expanding minority groups. This study compared the outcomes of South Asian patients with oral squamous cell carcinoma to the general population at a Canadian cancer center. In total, 697 patients who underwent surgery for oral squamous cell carcinoma between 2009 and 2022 were evaluated, with South Asian patients constituting 9% of the cohort. Despite similar tumor characteristics and treatments, South Asian patients had double the risk of cancer recurrence and significantly worse survival compared to non-South Asian patients. Understanding the association between South Asian ethnicity and outcomes in OSCC is crucial for informing public health initiatives to meet the distinctive needs of this population, thus fostering a more inclusive and supportive environment. (1) Background: To compare oncologic outcomes of South Asian (SA) patients treated for oral squamous cell carcinoma (OSCC) to the general population. (2) Methods: Adult patients who underwent surgical resection of OSCC +/− adjuvant treatment between 2009 and 2022 (N = 697) at a regional cancer centre in Canada were included. SA patients, identified using a validated method, were compared to non-SA patients. Kaplan–Meier methods were used to compare the primary outcomes, disease-specific survival (DSS) and recurrence-free survival (RFS) across baseline univariate characteristics, including betel nut consumption. Median follow-up time was 36.4 months. Cox proportional hazard models were used to identify independent predictors of survival with significance set at p < 0.05. (3) Results: SA patients (9% of cohort, N = 64) were significantly younger and had lower rates of smoking and alcohol consumption compared to non-SA patients (p < 0.05). SA patients had a two-fold higher risk of recurrence and significantly worse disease-specific survival, even after adjusting for stage and high-risk features [RFS: HR 2.01 (1.28–3.14), DSS: HR 1.79 (1.12–2.88)]. The consumption of betel nut was not associated with outcomes. (4) Conclusions: SA patients had significantly worse oncologic outcomes, even after controlling for known predictors of poor prognosis. These findings are novel and can inform personalized treatment decisions and influence public health policies when managing patients with different ethnic backgrounds. [ABSTRACT FROM AUTHOR]

Simple Summary: The current approach to breast cancer screening, which is based on a person's age, overlooks individual-level differences in breast cancer risk. As a result, many people are over- or under-screened according to their actual risk of breast cancer. Risk-stratified breast screening may overcome the limitations of age-based screening, but there are still many knowledge gaps regarding how best to implement it in the population setting. This study will generate the first Canadian evidence on the adoption of breast cancer risk assessment in the population setting, to support the future implementation of risk-stratified breast cancer screening. This study demonstrated that, while risk assessment for risk-stratified screening at the population level is feasible, an equity lens must be considered in implementation to ensure cancer-screening disparities are not widened. Risk-stratified breast screening has been proposed as a strategy to overcome the limitations of age-based screening. A prospective cohort study was undertaken within the PERSPECTIVE I&I project, which will generate the first Canadian evidence on multifactorial breast cancer risk assessment in the population setting to inform the implementation of risk-stratified screening. Recruited females aged 40–69 unaffected by breast cancer, with a previous mammogram, underwent multifactorial breast cancer risk assessment. The adoption of multifactorial risk assessment, the effectiveness of methods for collecting risk factor information and the costs of risk assessment were examined. Associations between participant characteristics and study sites, as well as data collection methods, were assessed using logistic regression; all p-values are two-sided. Of the 4246 participants recruited, 88.4% completed a risk assessment, with 79.8%, 15.7% and 4.4% estimated at average, higher than average and high risk, respectively. The total per-participant cost for risk assessment was CAD 315. Participants who chose to provide risk factor information on paper/telephone (27.2%) vs. online were more likely to be older (p = 0.021), not born in Canada (p = 0.043), visible minorities (p = 0.01) and have a lower attained education (p < 0.0001) and perceived fair/poor health (p < 0.001). The 34.4% of participants requiring risk factor verification for missing/unusual values were more likely to be visible minorities (p = 0.009) and have a lower attained education (p ≤ 0.006). This study demonstrates the feasibility of risk assessment for risk-stratified screening at the population level. Implementation should incorporate an equity lens to ensure cancer-screening disparities are not widened. [ABSTRACT FROM AUTHOR]

Simple Summary: The quality of life of patients with facial basal cell carcinoma significantly improves after surgery. Nevertheless, it remains inferior to those without the disease. Facial scarring has been identified as a contributing factor to adverse psychosocial changes. In this study, we explore the aesthetic assessment of facial scars within this specific patient group, aiming to uncover potential correlations between the severity of scars and the quality of life. This study comprises two phases as follows: scale validation and pilot with a sample size of 100 patients. The Lithuanian version of the POSAS 2.0 was established after a thorough psychometric evaluation, surpassing acceptable validity thresholds. The pilot phase findings show a notable improvement in scars during the later stages of postoperative recovery, with the initial identification of specific groups that perceive their scars more negatively. Given the observed correlations between the scar assessment and the quality of life, this study highlights the crucial role of addressing the aesthetic satisfaction of patients with surgically treated basal cell carcinoma. Facial basal cell carcinoma (BCC) surgery enhances the quality of life (QoL) but leaves patients with inferior QoL, presumably caused by scarring, emphasizing the need to understand post-surgery aesthetic satisfaction. This study aimed to validate the Lithuanian version of the Patient and Observer Scar Assessment Scale (POSAS) 2.0 and utilise it to identify scar evaluation differences and correlations among POSAS scores and specific aesthetic facial regions, age, gender, surgery types, and short- and long-term QoL. Employing a prospective longitudinal design, 100 patients with facial scars after surgical BCC removal were enrolled. The validation phase confirmed the translated POSAS 2.0 psychometric properties, while the pilot phase used statistical analyses to compare scores among demographic and clinical groups and evaluate correlations between scar assessment and QoL. The findings indicate that the translated Lithuanian version of POSAS 2.0 exhibits good psychometric properties, revealing insights into aesthetic satisfaction with post-surgical facial scars and their impact on QoL. The Lithuanian version of the POSAS 2.0 was established as a valid instrument for measuring post-surgical linear scars. QoL with scar assessment statistically significantly correlates, 6 months after surgery, with worse scores, particularly notable among women, younger patients, and those with tumours in the cheek region. [ABSTRACT FROM AUTHOR]

Simple Summary: Ramucirumab (RAM) + docetaxel (DTX) therapy is recommended as a second-line treatment for non-small cell lung cancer (NSCLC) and pretreatment with immune checkpoint inhibitors (ICIs) has been reported to improve the therapeutic efficacy of this therapy. Meanwhile, caution should be exercised for the development of febrile neutropenia during this treatment and preventing the onset of neutropenia while continuing the treatment is greatly important. This study found that previous treatment with ICIs reduced the incidence of grade ≥ 3 neutropenia after RAM + DTX therapy in patients with NSCLC, regardless of the influences of pretreatment with cytotoxic anticancer agents. A history of ICI treatment may have a similar influence on carcinomas other than NSCLC. In the present study, the influence of previous immune checkpoint inhibitor (ICI) therapy with ramucirumab (RAM) + docetaxel (DTX) therapy on the occurrence of severe neutropenia in patients with non-small cell lung cancer (NSCLC) was evaluated, taking into account the influences of cytotoxic chemotherapy used in pretreatment. The study participants included patients who received a combination therapy of RAM and DTX as cancer chemotherapy for NSCLC. The influences of previous ICI treatment and pretreatment with cytotoxic anticancer agents on the development of grade ≥ 3 neutropenia were analysed. A total of 89 patients, including 50 with and 39 without a history of ICI treatment, were analysed. Kaplan-Meier curves showed a significant difference in the influence of previous ICI treatment on the development of grade ≥ 3 neutropenia (p = 0.006). Moreover, Cox regression analysis identified a history of ICI treatment and prophylactic administration of G-CSF as factors associated with the development of grade ≥ 3 neutropenia (p = 0.018 and p < 0.001, respectively). This study found that previous treatment with ICIs reduced the incidence of grade ≥ 3 neutropenia after RAM + DTX therapy in patients with NSCLC, regardless of the influences of pretreatment with cytotoxic anticancer agents. [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: In the last few decades, studies have found many common genetic variants linked to breast cancer. Most of these variants are in non-coding regions or regions that do not directly affect gene function. This study aims to see if a polygenic risk score (PRS) based on functional variants could better predict breast cancer risk compared to an established 313-variant breast cancer PRS. Using publicly available summary data from GWASs, and Quantitative Trait Locus studies of gene expression and DNA methylation, we identified 149 variants potentially causally linked to the risk of developing breast cancer; the weighted sum of these variants was designated as the functional variant. The functional PRS was less effective at predicting breast cancer than the established PRS in 3560 breast cancer patients and 3383 non-breast cancer individuals. Combining both scores did not substantially enhance the prediction accuracy of the established PRS. Purpose: To assess the association of a polygenic risk score (PRS) for functional genetic variants with the risk of developing breast cancer. Methods: Summary data-based Mendelian randomization (SMR) and heterogeneity in dependent instruments (HEIDI) were used to identify breast cancer risk variants associated with gene expression and DNA methylation levels. A new SMR-based PRS was computed from the identified variants (functional PRS) and compared to an established 313-variant breast cancer PRS (GWAS PRS). The two scores were evaluated in 3560 breast cancer cases and 3383 non-cancer controls and also in a prospective study (n = 10,213) comprising 418 cases. Results: We identified 149 variants showing pleiotropic association with breast cancer risk (eQTLHEIDI > 0.05 = 9, mQTLHEIDI > 0.05 = 165). The discriminatory ability of the functional PRS (AUCcontinuous [95% CI]: 0.540 [0.526 to 0.553]) was found to be lower than that of the GWAS PRS (AUCcontinuous [95% CI]: 0.609 [0.596 to 0.622]). Even when utilizing 457 distinct variants from both the functional and GWAS PRS, the combined discriminatory performance remained below that of the GWAS PRS (AUCcontinuous, combined [95% CI]: 0.561 [0.548 to 0.575]). A binary high/low-risk classification based on the 80th centile PRS in controls revealed a 6% increase in cases using the GWAS PRS compared to the functional PRS. The functional PRS identified an additional 12% of high-risk cases but also led to a 13% increase in high-risk classification among controls. Similar findings were observed in the SCHS prospective cohort, where the GWAS PRS outperformed the functional PRS, and the highest-performing PRS, a combined model, did not significantly improve over the GWAS PRS. Conclusions: While this study identified potentially functional variants associated with breast cancer risk, their inclusion did not substantially enhance the predictive accuracy of the GWAS PRS. [ABSTRACT FROM AUTHOR]

Simple Summary: Improvements in lung cancer risk assessment to inform on the need for screening may be achieved through the use of biomarkers. Here, we report the findings of a validation study of a panel of four circulating protein biomarkers for the risk prediction of lung cancer in a cohort of pre-diagnostic plasmas obtained from the Physician's Health Study (PHS). We demonstrate that the protein panel can identify individuals at high risk of lung cancer up to two years prior to clinical diagnosis. This study aimed to assess a four-marker protein panel (4MP)'s performance, including the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19, for predicting lung cancer in a cohort enriched with never- and ever-smokers. Blinded pre-diagnostic plasma samples collected within 2 years prior to a lung cancer diagnosis from 25 cases and 100 sex-, age-, and smoking-matched controls were obtained from the Physicians' Health Study (PHS). The 4MP yielded AUC performance estimates of 0.76 (95% CI: 0.61–0.92) and 0.69 (95% CI: 0.56–0.82) for predicting lung cancer within one year and within two years of diagnosis, respectively. When stratifying into ever-smokers and never-smokers, the 4MP had respective AUCs of 0.77 (95% CI: 0.63–0.92) and 0.72 (95% CI: 0.17–1.00) for a 1-year risk of lung cancer. The AUCs of the 4MP for predicting metastatic lung cancer within one year and two years of the blood draw were 0.95 (95% CI: 0.87–1.00) and 0.78 (95% CI: 0.62–0.94), respectively. Our findings indicate that a blood-based biomarker panel may be useful in identifying ever- and never-smokers at high risk of a diagnosis of lung cancer within one-to-two years. [ABSTRACT FROM AUTHOR]

Simple Summary: This multicenter study (n = 1133, inclusion criteria: 3.5 cm maximum tumor size and preoperative indication for a boost) provides detailed data on acute and long-term toxicities in breast cancer patients undergoing breast-conserving surgery combined with an anticipated intraoperative boost with low-energy X-rays followed by whole breast irradiation. Toxicity assessments, based on LENT SOMA criteria, were performed annually up to 10 years of follow-up. IORT boost was completed in 90% and EBRT in 97% of cases. No grade 3 or 4 acute toxicities were observed, with mild acute side effects reported in a small proportion of patients. Chronic toxicities were seen in 16.2% of patients with teleangiectasia, 14.3% with grade ≥ 2 fibrosis, 3.4% with grade ≥ 2 pain, and 1.1% with hyperpigmentation. The results show that the therapy is safe and feasible in terms of toxicity and confirms intraoperative boost as a standard method of boost application in a large prospective cohort. In the context of breast cancer treatment optimization, this study prospectively examines the feasibility and outcomes of utilizing intraoperative radiotherapy (IORT) as a boost in combination with standard external beam radiotherapy (EBRT) for high-risk patients. Different guidelines recommend such a tumor bed boost in addition to whole breast irradiation with EBRT for patients with risk factors for local breast cancer recurrence. The TARGIT BQR (NCT01440010) is a prospective, multicenter registry study aimed at ensuring the quality of clinical outcomes. It provides, for the first time, data from a large cohort with a detailed assessment of acute and long-term toxicity following an IORT boost using low-energy X-rays. Inclusion criteria encompassed tumors up to 3.5 cm in size and preoperative indications for a boost. The IORT boost, administered immediately after tumor resection, delivered a single dose of 20 Gy. EBRT and systemic therapy adhered to local tumor board recommendations. Follow-up for toxicity assessment (LENT SOMA criteria: fibrosis, teleangiectasia, retraction, pain, breast edema, lymphedema, hyperpigmentation, ulceration) took place before surgery, 6 weeks to 90 days after EBRT, 6 months after IORT, and then annually using standardized case report forms (CRFs). Between 2011 and 2020, 1133 patients from 10 centers were preoperatively enrolled. The planned IORT boost was conducted in 90%, and EBRT in 97% of cases. Median follow-up was 32 months (range 1–120, 20.4% dropped out), with a median age of 61 years (range 30–90). No acute grade 3 or 4 toxicities were observed. Acute side effects included erythema grade 1 or 2 in 4.4%, palpable seroma in 9.1%, punctured seroma in 0.3%, and wound healing disorders in 2.1%. Overall, chronic teleangiectasia of any grade occurred in 16.2%, fibrosis grade ≥ 2 in 14.3%, pain grade ≥ 2 in 3.4%, and hyperpigmentation in 1.1%. In conclusion, a tumor bed boost through IORT using low-energy X-rays is a swift and feasible method that demonstrates low rates in terms of acute or long-term toxicity profiles in combination with whole breast irradiation. [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: Laryngeal squamous cell carcinomas (LSCC) are the third most common type of head and neck cancer. Approximately 40% of LSCC cases present with locally advanced carcinomas at diagnosis. The poor prognosis is mainly attributed to late diagnosis. Biomarkers capable of predicting LSCC at early stages are needed. We identified and validated exosomal insulin-like growth factor binding protein 7 (IGFBP7) and Annexin A1 (ANXA1) as promising exosomal biomarkers for LSCC detection. Background: The lack of screening methods for LSCC is a critical issue, as treatment options and the treatment outcome greatly depend on the stage of LSCC at initial diagnosis. Therefore, the objective of this study was to identify potential exosomal serum biomarkers that can diagnose LSCC and distinguish between early- and late-stage disease. Methods: A multiplexed proteomic array was used to identify differentially expressed proteins in exosomes isolated from the serum samples of LSCC patients compared to the control group (septorhinoplasty, SRP). The most promising proteins for diagnosis and differentiation were calculated using biostatistical methods and were validated by immunohistochemistry (IHC), Western blots (WB), and ELISA. Results: Exosomal insulin-like growth factor binding protein 7 (IGFBP7) and Annexin A1 (ANXA1) were the most promising exosomal biomarkers for distinguishing between control and LSCC patients and also between different stages of LSCC (fold change up to 15.9, p < 0.001 for all). Conclusion: The identified proteins represent potentially novel non-invasive biomarkers. However, these results need to be validated in larger cohorts with a long-term follow-up. Exosomal biomarkers show a superior signal-to-noise ratio compared to whole serum and may therefore be an important tool for non-invasive biomarker profiling for laryngeal carcinoma in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Rehabilitation might play a crucial role in malignant pleural mesothelioma (MPM), but its role is still debated in MPM patients. The intervention comprised multidisciplinary educational sessions, physical rehabilitation, and respiratory physiotherapy. Feasibility was evaluated based on dropout rates, adherence to the rehabilitation program, safety, and patient-reported outcomes. In light of the current evidence, we have conducted a pilot study to assess the feasibility of tailored pulmonary rehabilitation in terms of physical and respiratory function in MPM. Twelve patients were initially enrolled, with seven completing the study. High adherence to physical (T1: 93.43%, T2: 82.56%) and respiratory (T1: 96.2%, T2: 92.5%) rehabilitation was observed, with minimal adverse events reported. Patient satisfaction remained high throughout the study (GPE scores at T1: 1.83 ± 1.17; T2: 2.0 ± 1.15), with improvements noted in physical function, pain management, and health-related quality of life. Despite its promising outcomes, further research with larger samples is warranted to validate its efficacy and integrate rehabilitation as a component into the multidisciplinary management of MPM. Malignant pleural mesothelioma (MPM) represents a significant health burden, with limited treatment options and poor prognosis. Despite advances in pharmacological and surgical interventions, the role of rehabilitation in MPM management remains underexplored. This study aims to assess the feasibility of a tailored pulmonary rehabilitation intervention addressing physical and respiratory function in MPM patients. A prospective pilot study was conducted on surgically treated MPM patients referred to a cardiopulmonary rehabilitation service. The intervention comprised multidisciplinary educational sessions, physical rehabilitation, and respiratory physiotherapy. Feasibility was evaluated based on dropout rates, adherence to the rehabilitation program, safety, and patient-reported outcomes. Twelve patients were initially enrolled, with seven completing the study. High adherence to physical (T1: 93.43%, T2: 82.56%) and respiratory (T1: 96.2%, T2: 92.5%) rehabilitation was observed, with minimal adverse events reported. Patient satisfaction remained high throughout the study (GPE scores at T1: 1.83 ± 1.17; T2: 2.0 ± 1.15), with improvements noted in physical function, pain management, and health-related quality of life. However, some issues, such as time constraints and lack of continuous supervision, were reported by participants. This pilot study demonstrates the feasibility and potential benefits of a tailored pulmonary rehabilitation intervention in MPM patients. Despite its promising outcomes, further research with larger samples is warranted to validate its efficacy and integrate rehabilitation as a component into the multidisciplinary management of MPM. [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: Due to the location of the right ventricle in the anterior part of the chest, it is particularly vulnerable to damage during radiotherapy, for example, in the treatment of lung cancer. The aim of this prospective study was to compare the effect of radiochemotherapy versus chemotherapy on right ventricular systolic function, assessed using multiple echocardiographic variables. In all patients, echocardiography was performed before the start of treatment, after its completion, and three months after its completion. The analysis of the results included, among others, the radiation dose received by the entire heart and its individual chambers and coronary vessels. The obtained results make it possible to assess the scale of the problem of right ventricular damage after chest radiotherapy and to assess the risk factors associated with the occurrence of this complication. Background: Anticancer treatment is associated with many side effects, including those involving the cardiovascular system. While many studies are available on the effects of radiotherapy (RT) on the left ventricle (LV), studies are lacking on the early effects of RT on the structure and function of the right ventricle (RV). Our study aims to assess, using modern echocardiographic techniques, the effect of irradiation on RV systolic function in the mid-term follow-up of patients undergoing RT for lung cancer (LC). Methods: This single-center, prospective study included consecutive patients with LC who were referred for treatment with definite radiotherapy and chemotherapy (study group) or chemotherapy only (control group). Results: The study included 43 patients with a mean age of 64.9 ± 8.1 years. Cancer treatment-related RV toxicity (CTR-RVT) was found in 17 patients (40%). Early reductions in TAPSE values were observed among patients in the study group (20.3 mm vs. 22.1 mm, p = 0.021). Compared to baseline, there was a significant reduction in RV global longitudinal strain (RV GLS) in the study group immediately after the treatment (−21.1% vs. −18.4%, p = 0.02) and also at 3 months after RT (−21.1% vs. −19.1%, p = 0.021). A significant reduction in the RV FWLS value was also observed at 3 months after the end of the treatment (−23.8% vs. −21.8, p = 0.046). There were no significant changes in the three-dimensional right ventricular ejection fraction (3DRVEF) during the follow-up. We found a correlation (p = 0.003) between the mean dose of radiation to the RV and 3DRVEF when assessed immediately after RT. The mean dose of radiation to the heart correlated with RV free-wall longitudinal strain (RV FWLS) immediately after RT (p = 0.03). Conclusions: RV cardiotoxicity occurs in nearly half of patients treated for lung cancer. TAPSE is an important marker of deterioration of RV function under LC treatment. Compared to 3DRVEF, speckle tracking echocardiography is more useful in revealing deterioration of RV systolic function after radiotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Little is known about the differences in liver cancer care between liver cancer referral centres, with and without an integrated liver transplant program. Even after adjusting for other important factors, such as tumour stage and patient characteristics, we found that liver transplant centres systematically used different local cancer treatments compared to non-transplant centres. Patients managed at liver transplant centres showed improved overall survival, which was evident even after considering the increased rates of transplantation. The management of early-stage hepatocellular carcinoma (HCC) is complex, with multiple treatment strategies available. There is a paucity of literature regarding variations in the patterns of care and outcomes between transplant and non-transplant centres. We conducted this real-world multi-centre cohort study in two liver cancer referral centres with an integrated liver transplant program and an additional eight non-transplant HCC referral centres across Australia to identify variation in patterns of care and key survival outcomes. Patients with stage Barcelona Clinic Liver Cancer (BCLC) 0/A HCC, first diagnosed between 1 January 2016 and 31 December 2020, who were managed at a participating site, were included in the study. Patients were excluded if they had a history of prior HCC or if they received upfront liver transplantation. A total of 887 patients were included in the study, with 433 patients managed at a liver cancer centre with a transplant program (LTC) and 454 patients managed at a non-transplant centre (NTC). Management at an LTC did not significantly predict allocation to resection (adjusted OR 0.75, 95% CI 0.50 to 1.11, p = 0.148). However, in those not receiving resection, LTC and NTC patients were systematically managed differently, with LTC patients five times less likely to receive upfront ablation than NTC patients (adjusted OR 0.19, 95% CI 0.13 to 0.28, p < 0.001), even after adjusting for tumour burden, as well as for age, gender, liver disease aetiology, liver disease severity, and medical comorbidities. LTCs exhibited significantly higher proportions of patients undergoing TACE for every tumour burden category, including those with a single tumour measuring 2 cm or less (p < 0.001). Using multivariable Cox proportional hazards analysis, management at a transplant centre was associated with reduced all-cause mortality (adjusted HR 0.71, 95% CI 0.51 to 0.98, p = 0.036), and competing-risk regression analysis, considering liver transplant as a competing event, demonstrated a similar reduction in risk (adjusted HR 0.70, 95% CI 0.50 to 0.99, p = 0.041), suggesting that the reduced risk of death is not fully explained by higher rates of transplantation. Our study highlights systematic differences in HCC care between large volume liver transplant centres and other sites, which has not previously been well-described. Further work is needed to better define the reasons for differences in treatment allocation and to aim to minimise unwarranted treatment variation to maximise patient outcomes across Australia. [ABSTRACT FROM AUTHOR]

Simple Summary: The evaluation of therapeutic approaches over a decade at a tertiary cancer center in Germany was undertaken due to the frequent and critical discussions surrounding the selection of chemotherapy regimens and the incorporation of prophylactic cranial irradiation (PCI) in the management of limited disease small cell lung cancer (LD-SCLC). We found significant differences in progression-free survival (PFS) and overall survival (OS) between patients treated with carboplatin and etoposide (CP) and those treated with cisplatin and etoposide (EP), with EP showing better outcomes. Concomitant chemotherapy was also associated with improved PFS and OS. Notably, PCI was found to significantly improve OS and showed a trend towards improved PFS. Female patients had better OS, and the type of chemotherapy and PCI remained independent predictors of survival. This research provides valuable insights into treatment patterns, outcomes, and survival predictors for LD-SCLC, emphasizing the importance of personalized treatment approaches and the potential benefits of PCI. However, the study's retrospective nature and sample-size limitations should be considered, highlighting the need for further prospective studies in this field. In this study, we investigated the outcomes and factors influencing treatment efficacy in 93 patients with limited disease small cell lung cancer (LD-SCLC), with a median age of 64 years. We focused on the impact of chemotherapy regimens, prophylactic cranial irradiation (PCI), and patient-related variables. The median follow-up for OS was 17.3 months. We observed a statistically significant difference in PFS between LD-SCLC patients treated with cisplatin and etoposide (EP) and those treated with carboplatin and etoposide (CP) (PFS: EP 13.63 months vs. CP 6.54 months, p < 0.01). Patients treated with EP had better overall survival (OS) than CP-treated patients (OS: EP 26.9 months vs. CP 16.16 months, p < 0.01). Concomitant chemotherapy was associated with improved PFS (p = 0.003) and OS (p = 0.002). Patients receiving PCI showed superior OS (p = 0.05) and a trend towards improved PFS (p = 0.057). Female gender was associated with better OS (p = 0.025). Most patients had an ECOG performance status of 0 (71%). This real-world study underscores the importance of multidisciplinary LD-SCLC management, emphasizing the roles of chemotherapy, radiotherapy, and PCI. These findings inform personalized treatment strategies and emphasize the need for prospective trials to validate these results and optimize LD-SCLC treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is one of the most diagnosed malignancies among women worldwide, affecting 18,000 women annually in the Netherlands. As life expectancy increases, monitoring quality of life (QoL) using Patient-Reported Outcome Measures (PROMs) becomes more important. The EQ-5D-5L and the EORTC QLQ-C30 are two widely used PROMs in the Netherlands. For utilizing PROMs in research and clinical care, internal responsiveness is key. Given the broad application of these PROMs in the Netherlands and the fact that internal responsiveness varies based on the disease, treatment regime, and geographical factors, this study assesses and compares the internal responsiveness of the EQ-5D-5L and the EORTC QLQ-C30 among Dutch breast cancer patients during the first year post-surgery. The results demonstrated that the EQ-5D-5L and the EORTC QLQ-C30 have small internal responsiveness (<0.5) at 6- and 12 months post-surgery. These findings provide crucial insights for interpreting outcomes from both PROMs in research and clinical practice. The EuroQoL 5-Dimension 5-Level questionnaire (EQ-5D-5L) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) are commonly used Patient-Reported Outcome Measures (PROMs) for breast cancer. This study assesses and compares the internal responsiveness of the EQ-5D-5L and EORTC QLQ-C30 in Dutch breast cancer patients during the first year post-surgery. Women diagnosed with breast cancer who completed the EQ-5D-5L and EORTC QLQ-C30 pre-operatively (T0), 6 months (T6), and 12 months post-surgery (T12) were included. Mean differences of the EQ-5D-5L and EORTC QLQ-C30 between baseline and 6 months (delta 1) and between baseline and 12 months post-surgery (delta 2) were calculated and compared against the respective minimal clinically important differences (MCIDs) of 0.08 and 5. Internal responsiveness was assessed using effect sizes (ES) and standardized response means (SRM) for both deltas. In total, 333 breast cancer patients were included. Delta 1 and delta 2 for the EQ-5D-5L index and most scales of the EORTC QLQ-C30 were below the MCID. The internal responsiveness for both PROMs was small (ES and SRM < 0.5), with greater internal responsiveness for delta 1 compared to delta 2. The EQ-5D-5L index showed greater internal responsiveness than the EORTC QLQ-C30 Global Quality of Life scale and summary score. These findings are valuable for the interpretation of both PROMs in Dutch breast cancer research and clinical care. [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: 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: 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: 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: 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: Our study explores the capability of dynamic contrast-enhanced MRI (DCE-MRI) as an early predictor of disease progression in glioblastoma patients, compared to conventional MRI. We analyzed two cohorts comprising 26 patients with newly diagnosed primary glioblastoma. Patients were then categorized based on disease stage (progression or stability) and underwent three DCE-MRI scans prior to progression or consecutively for stable disease. Parameters such as Ktrans and plasma volume (Vp) were measured within the volume of interest (VOIs). Our findings revealed a gradual increase in Vp max values preceding disease progression in patients who underwent routine MRI scans. Utilizing quantitative DCE-MRI may offer an opportunity to detect disease progression earlier than conventional methods, potentially improving patient management by enabling proactive measures against progression. Background and Purpose: Distinguishing treatment-induced imaging changes from progressive disease has important implications for avoiding inappropriate discontinuation of a treatment. Our goal in this study is to evaluate the utility of dynamic contrast-enhanced (DCE) perfusion MRI as a biomarker for the early detection of progression. We hypothesize that DCE-MRI may have the potential as an early predictor for the progression of disease in GBM patients when compared to the current standard of conventional MRI. Methods: We identified 26 patients from 2011 to 2023 with newly diagnosed primary glioblastoma by histopathology and gross or subtotal resection of the tumor. Then, we classified them into two groups: patients with progression of disease (POD) confirmed by pathology or change in chemotherapy and patients with stable disease without evidence of progression or need for therapy change. Finally, at least three DCE-MRI scans were performed prior to POD for the progression cohort, and three consecutive DCE-MRI scans were performed for those with stable disease. The volume of interest (VOI) was delineated by a neuroradiologist to measure the maximum values for Ktrans and plasma volume (Vp). A Friedman test was conducted to evaluate the statistical significance of the parameter changes between scans. Results: The mean interval between subsequent scans was 57.94 days, with POD-1 representing the first scan prior to POD and POD-3 representing the third scan. The normalized maximum Vp values for POD-3, POD-2, and POD-1 are 1.40, 1.86, and 3.24, respectively (FS = 18.00, p = 0.0001). It demonstrates that Vp max values are progressively increasing in the three scans prior to POD when measured by routine MRI scans. The normalized maximum Ktrans values for POD-1, POD-2, and POD-3 are 0.51, 0.09, and 0.51, respectively (FS = 1.13, p < 0.57). Conclusions: Our analysis of the longitudinal scans leading up to POD significantly correlated with increasing plasma volume (Vp). A longitudinal study for tumor perfusion change demonstrated that DCE perfusion could be utilized as an early predictor of tumor progression. [ABSTRACT FROM AUTHOR]

Simple Summary: Angiosarcoma is a rare type of soft tissue sarcoma with a progressive and unpredictable disease course. Currently, surgery is the only well-defined treatment option. Adjuvant oncological treatment remains inconclusive. In effort to provide evidence for improved management and follow-up, the purpose of this study was to assess treatment outcomes and identify prognostic factors. We identified a nation-wide cohort of 154 patients with complete follow-up. Adjuvant oncological treatment did not benefit overall survival, risk of metastasis, or recurrence. Cutaneous tumors, surgery, and negative margin showed improved overall survival, yet without reducing the risk of recurrence and metastasis, resulting in a grave overall survival rate. Angiosarcoma is a rare aggressive and understudied soft tissue sarcoma with pending evidence-based treatment guidelines due to varying study cohorts and inconsistent outcome measures. Surgery with wide resection is currently considered to be the cornerstone in management. In a population-based cohort identified from Danish National Health Registers between 2000 and 2017, this study aimed to define prognostic factors in patients with newly diagnosed soft tissue angiosarcoma. Kaplan–Meier survival analysis demonstrated 5-year overall survival of 28%. Competing risk analysis demonstrated cumulative incidence of local recurrence of 30% and metastasis of 43%. Multivariable Cox models among 154 included patients demonstrated age above 60 years and metastasis to be independently associated with worse overall survival. Cutaneous tumors, surgery, and negative resection margin were independently associated with improved overall survival. Adjuvant oncological treatment did not improve overall survival, risk of metastasis, or recurrence. Negative margin was not associated with lower risk of recurrence and metastasis. We conclude that, despite demonstrated improved survival after surgery with wide resection, overall survival remains poor. [ABSTRACT FROM AUTHOR]

Simple Summary: Abemaciclib in combination with endocrine therapy is a standard first- or later-line of treatment for HR+/HER2− metastatic breast cancer (MBC). Real-world studies provide valuable addition to pivotal trials by including a heterogeneous patient population, particularly subgroups that are often underrepresented (e.g., elderly patients). This study retrospectively collected data on the efficacy and safety of abemaciclib in a real-world patient population. The safety and efficacy of the treatment were consistent with the pivotal studies, including in elderly patients. Comparable survival outcomes were observed between the first two lines of treatment. Additionally, metastatic disease survival was greatly prolonged, exceeding 5 years compared to historical data. The study provides further reassurance that dose reductions do not affect survival. The safety profile of abemaciclib was consistent with previous findings, and no new adverse events (AEs) were identified. Although abemaciclib was well tolerated in elderly patients, the careful monitoring and management of AEs is still warranted. (1) Background: Abemaciclib combined with endocrine therapy is a standard first- or later-line of treatment for HR+/HER2− metastatic breast cancer (MBC). The aim of this retrospective cohort study was to describe the outcomes of patients treated in a real-world setting, with particular focus on elderly patients. (2) Patients and methods: Patients treated with abemaciclib between November 2019 and February 2022 were included in the study. Data were collected from electronic medical records. The primary objective was to determine real-world progression-free survival (rwPFS), and secondary objectives included median overall survival (mOS) and safety. (3) Results: Analysis included 134 patients, with a median follow-up of 42 months. Median age was 62 years, with 29.9% aged 70+ years. A total of 51.5% of patients received abemaciclib in first-line, predominantly with aromatase inhibitor (68.1%). Median rwPFS was 21 in first-line and 20 months in the second-line, with no significant difference between treatment lines (HR 0.96; p = 0.88). Patients treated in the third- or later-line had a significantly shorter rwPFS, at 7 months (HR 1.48, p = 0.003). mOS was not reached in the first-line setting. For second- and third- or later-lines, mOS was 29 and 19 months, respectively. There was no significant difference in mOS between first- or second-line (HR 1.37, p = 0.36). In the 70+ group, median rwPFS was 15 months and mOS was 25 months with no significant difference compared to younger patients (rwPFS HR 1.1; p = 0.65; OS HR 1.4; p = 0.21). Most common adverse events (AEs) were diarrhoea (68.7%), anaemia (64.9%), and increased serum creatinine (63.4%). Grade 3/4 AEs were reported in 21.6% of patients. Dose reductions occurred in 30.6% of patients and were more frequent in patients 70+ (40%) compared to younger patients (28%); the difference was not significant (p = 0.22). At study cut-off, 64.9% of patients discontinued abemaciclib, primarily due to disease progression (73.5%). (4) Conclusions: Our study provides valuable insights into the effectiveness and safety of abemaciclib for the treatment of MBC. We observed comparable outcomes in terms of rwPFS and OS between the first two lines, suggesting consistent effectiveness across treatment lines. In addition, our findings suggest that older age (70+) does not significantly impact the effectiveness and tolerability of abemaciclib, although the careful monitoring and management of AEs are warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: With the introduction of antibody–drug conjugates (ADCs), novel treatment options for advanced and recurrent cervical cancer might be found. The expression of their target proteins in cervical cancer is largely unknown. This study addresses this issue by analyzing gene and protein expression of potential novel ADC targets in cervical cancer. (1) Background: There is a huge unmet clinical need for novel treatment strategies in advanced and recurrent cervical cancer. Several cell membrane-bound molecules are up-regulated in cancer cells as compared to normal tissue and have revived interest with the introduction of antibody–drug conjugates (ADCs). (2) Methods: In this study, we characterize the expression of 10 potential ADC targets, TROP2, mesotheline, CEACAM5, DLL3, folate receptor alpha, guanylatcyclase, glycoprotein NMB, CD56, CD70 and CD138, on the gene expression level. Of these, the three ADC targets TROP2, CEACAM5 and CD138 were further analyzed on the protein level. (3) Results: TROP2 shows expression in 98.5% (66/67) of cervical cancer samples. CEACAM5 shows a stable gene expression profile and overall, 68.7% (46/67) of cervical cancer samples are CEACAM-positive with 34.3% (23/67) of cervical cancer samples showing at least moderate or high expression. Overall, 73.1% (49/67) of cervical cancer samples are CD138-positive with 38.8% (26/67) of cervical cancer samples showing at least moderate or high expression. (4) Conclusions: TROP2, CEACAM5 or CD138 do seem suitable for further clinical research and the data presented here might be used to guide further clinical trials with ADCs in advanced and recurrent cervical cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Spinal intradural tumors can grow along multiple segments. Extensive approaches such as long-segment laminoplasties may be necessary to achieve the gold standard of gross total resection. Here, we present a comprehensive cohort study describing the satisfying clinical outcome of patients undergoing four or more segment approaches without requiring dorsal fixation for intradural tumor resection. The clinical outcomes are comparable to patients undergoing surgical treatment of short-segment approaches, and no patient underwent a secondary fixation for symptoms of mechanical instability. Introduction: Spinal intradural tumors account for 15% of all CNS tumors. Typical tumor entities include ependymomas, astrocytomas, meningiomas, and neurinomas. In cases of multiple affected segments, extensive approaches may be necessary to achieve the gold standard of complete tumor resection. Methods: We performed a bicentric, retrospective cohort study of all patients equal to or older than 14 years who underwent multi-segment surgical treatment for spinal intradural tumors between 2007 and 2023 with approaches longer than four segments without instrumentation. We assessed the surgical technique and the clinical outcome regarding signs of symptomatic spinal instability. Children were excluded from our cohort. Results: In total, we analyzed 33 patients with a median age of 44 years and interquartile range IQR of 30–56 years, including the following tumors: 21 ependymomas, one subependymoma–ependymoma mixed tumor, two meningiomas, two astrocytomas, and seven patients with other entities. The median length of the approach was five spinal segments with a range of 4–14 and with the foremost localization in the cervical or thoracic spine. Laminoplasty was the most chosen approach (72.2%). The median time to follow-up was 13 months IQR (4–56 months). Comparing pre- and post-surgery outcomes, 72.2% of the patients (n = 24) reported pain improvement after surgery. The median modified McCormick scores pre- and post surgery were equal to II IQR (I–II) and II IQR (I–III), respectively. Discussion: We achieved satisfying results with long-segment approaches. In general, patients reported pain improvement after surgery and received similar low modified McCormick scores pre- and post surgery and did not undergo secondary dorsal fixation. Thus, we conclude that intradural tumor resection via extensive approaches does not seem to impair long-term spinal stability in our cohort. [ABSTRACT FROM AUTHOR]

Simple Summary: Individuals living with multiple myeloma are likely to have bone destruction as a consequence of their disease, leading healthcare providers to be reluctant to recommend physical activity. The aim of this prospective trial was to assess the feasibility of six-month strength training and walking interventions in patients with multiple myeloma. Various assessments of physical function and pain were performed at multiple timepoints throughout the trial. Participants saw improvements in mobility, leg strength, aerobic capacity, and endurance, with more pronounced and sustained improvements in the strength training arm, particularly in leg strength. This small trial showed the feasibility and benefits of both strength training and walking interventions in patients living with multiple myeloma. A larger trial extending these findings is underway at our institution. Because of the high prevalence of bone destruction in patients with multiple myeloma (MM), physical exercise is oftentimes discouraged by healthcare providers. The goal of this prospective trial was to investigate the feasibility of two six-month exercise interventions in patients with MM (N = 42): a remotely prompted home-based walking intervention or a supervised strength training intervention. Physical function and pain were assessed with the Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility Short Form raw score, a six-minute walk test (6 MWT), a 30-second sit-to-stand test (30 SST), a timed up-and-go (TUG) test, a visual analog scale (VAS) for pain, handheld dynamometer tests, heart rate at rest, blood oxygen saturation at rest, and body mass index. No intervention-related serious adverse events were observed. Adverse events mostly affected the musculoskeletal system. In the resistance training group (n = 24), patients showed significant improvements in AM-PAC, TUG, 6 MWT, and 30 SST, with all effects but the 6 MWT sustained six months after the intervention. The walking group (n = 18) saw improvements in the AM-PAC, TUG, 6 MWT, and 30 SST, with a sustained change in the AM-PAC and TUG. This trial shows the feasibility of both exercise interventions with a sustained beneficial effect on the physical functioning of a six-month strength training intervention and, to a lesser extent, a six-month unsupervised walking intervention. A larger study building on these findings is currently underway. [ABSTRACT FROM AUTHOR]

Simple Summary: Melanoma patients with high neutrophil counts often show impaired clinical response and poor prognosis, indicating that neutrophils can support melanoma progression. The precise mechanism responsible for this correlation, especially in the context of targeted therapy, still requires clarification. We show that peripheral blood neutrophils of patients with advanced melanoma are characterized by lower CD16 surface expression compared to healthy donors, which has been reported to be associated with tumor promotion. We provide evidence that melanoma cells under dual-targeted therapy can be protected in vitro by neutrophils from both patients and healthy donors. In addition, this protective effect is dependent on cell–cell contact, as well as on culture conditions, and is observed under nonadherence. Unraveling the mechanism, the interference with the protease activity of neutrophils reduced protection. Understanding the complex interaction of neutrophils and melanoma cells might aid in discovering methods to prevent the tumor-promoting effects by neutrophils in patients. Elevated levels of peripheral blood and tumor tissue neutrophils are associated with poorer clinical response and therapy resistance in melanoma. The underlying mechanism and the role of neutrophils in targeted therapy is still not fully understood. Serum samples of patients with advanced melanoma were collected and neutrophil-associated serum markers were measured and correlated with response to targeted therapy. Blood neutrophils from healthy donors and patients with advanced melanoma were isolated, and their phenotypes, as well as their in vitro functions, were compared. In vitro functional tests were conducted through nonadherent cocultures with melanoma cells. Protection of melanoma cell lines by neutrophils was assessed under MAPK inhibition. Blood neutrophils from advanced melanoma patients exhibited lower CD16 expression compared to healthy donors. In vitro, both healthy-donor- and patient-derived neutrophils prevented melanoma cell apoptosis upon dual MAPK inhibition. The effect depended on cell–cell contact and melanoma cell susceptibility to treatment. Interference with protease activity of neutrophils prevented melanoma cell protection during treatment in cocultures. The negative correlation between neutrophils and melanoma outcomes seems to be linked to a protumoral function of neutrophils. In vitro, neutrophils exert a direct protective effect on melanoma cells during dual MAPK inhibition. This study further hints at a crucial role of neutrophil-related protease activity in protection. [ABSTRACT FROM AUTHOR]

Simple Summary: Undifferentiated pleomorphic sarcomas (UPSs) represent 10–20% of all soft tissue sarcomas (STSs) and have quickly emerged as one of the more immune-sensitive types. There are few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and those with other high-grade pleomorphic STSs. This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center intended to describe the efficacy and toxicity of ICB in this particular group of patients. We find that our outcomes are comparable to those in the published literature and pose a question regarding the need to further evaluate the optimal sequencing of radiotherapy and prior lines of systemic therapy. Background: Undifferentiated pleomorphic sarcomas (UPSs) are amongst the most common subtypes of soft-tissue sarcomas. Few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and other high-grade pleomorphic STS patients are available. Purpose: The purpose of our study is to describe the efficacy and toxicity of ICB in patients with advanced UPSs and other high-grade pleomorphic sarcomas treated at our institution. Methods: This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center between 1 January 2015 and 1 January 2023. Patients included in trials for which results are not yet published were excluded. Results: Thirty-six patients with advanced/metastatic pleomorphic sarcomas were included. The median age was 52 years. A total of 26 patients (72%) had UPSs and 10 patients (28%) had other high-grade pleomorphic sarcomas. The median follow-up time was 8.8 months. The median PFS was 2.9 months. The 3-month PFS and 6-month PFS were 46% and 32%, respectively. The median OS was 12.9 months. The 12-month OS and 24-month OS were 53% and 29%, respectively. The best response, previous RT, and type of ICB treatment were significantly and independently associated with shorter PFS (p = 0.0012, p = 0.0019 and p = 0.036, respectively). No new safety signal was identified, and the toxicity was overall manageable with no toxic deaths and only four patients (11%) stopping treatment due to toxicity. Conclusions: Real-world retrospective data are consistent with the published literature, with a promising 6-month PFS of 32%. Partial or stable responders to ICB treatment have significantly improved PFS compared to progressors. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung metastases are a major challenge in advanced cancer treatment because they are common and difficult to manage. This study assesses the effectiveness of laser-assisted pulmonary metastasectomy, a surgical technique designed to minimize the removal of healthy lung tissue, thereby preserving lung function. By examining the recovery of lung function in 126 patients after surgery, we aim to fill the gap in long-term data on this procedure. The findings indicate that lung function, measured by the amount of air a person can forcefully exhale in one second, significantly recovers within a year post-surgery. This study demonstrates the benefits of laser-assisted surgery for patients with lung metastases, potentially influencing treatment decisions and improving patient outcomes by maintaining essential lung capacity. Preserving maximum lung function is a fundamental goal of parenchymal-sparing pulmonary laser surgery. Long-term studies for follow-up of lung function after pulmonary laser metastasectomy are lacking. However, a sufficient postoperative lung function is essential for quality of life and reduces potential postoperative complications. In this study, we investigate the extent of loss in lung function following pulmonary laser resection after three, six, and twelve months. We conducted a retrospective analysis using a prospective database of 4595 patients, focusing on 126 patients who underwent unilateral pulmonary laser resection for lung metastases from 1996 to 2022 using a 1318 nm Nd:YAG laser or a high-power pure diode laser. Results show that from these patients, a median of three pulmonary nodules were removed, with 75% presenting central lung lesions and 25% peripheral lesions. The median preoperative FEV1 was 98% of the predicted value, decreasing to 71% postoperatively but improving to 90% after three months, 93% after six months, and 96% after twelve months. Statistical analysis using the Friedman test indicated no significant difference in FEV1 between preoperative levels and those at six and twelve months post-surgery. The findings confirm that pulmonary laser surgery effectively preserves lung function over time, with patients generally regaining their preoperative lung function within a year, regardless of the metastases' location. [ABSTRACT FROM AUTHOR]

Simple Summary: Newly diagnosed type 2 diabetes mellitus is associated with a higher risk of cancer, possibly in young individuals with diabetes. While the incidence of cancer is mildly decreasing in the background population, it does not decrease in patients with type 2 diabetes. In non-diabetic persons, certain types of cancer also occur in young age, while the 60–69-year-old group dominates for cancer cases in patients with type 2 diabetes. The majority of the new cancer cases is recognized within 6 months after the diagnosis of diabetes. This may call for increased cancer surveillance in patients with newly diagnosed type 2 diabetes mellitus. (1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal of this study was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. After exclusion of cases of age < 18 years, with gestational diabetes, with polycystic ovary syndrome, and with type 1 and prevalent type 2 diabetes mellitus, the incident T2DM (approx. 50,000 cases yearly) and for comparison, the diabetes-free Hungarian adult population (approx. 7,000,000 cases yearly) was included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14–4.53), p < 0.0001. The risk of having cancer was age dependent. The incidence of cancer was declining in the non-diabetic but was unchanged in the T2DM population. The average lag time of diagnosing cancer after the detection of T2DM was 3.86 months. (4) Conclusions: Incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer patients presenting with at least 10 lesions at brain metastasis (BM) diagnosis usually receive palliative whole-brain radiotherapy (WBRT). Our institutional BM tumor board favors the use of stereotactic radiotherapy (SRT) as much as possible, even in this population. This approach leads to an excellent local control rate of BM, with a low toxicity and radio-necrosis rate. Close MRI surveillance every 2 months is necessary for early detection in cases of new BMs, and repeated brain SRT is feasible and safe. Less than half of the patients will require a subsequent brain SRT. Moreover, at one year, less than a quarter of patients require a salvage WBRT or die from a neurological progression (strategy success rate). Overall survival data seem favorable compared to historical outcomes after WBRT in this population. Purpose: to evaluate an SRT approach in patients with at least 10 lesions at the time of BM initial diagnosis. Methods: This is a monocentric prospective cohort of patients treated by SRT, followed by a brain MRI every two months. Subsequent SRT could be delivered in cases of new BMs during follow-up. The main endpoints were local control rate (LCR), overall survival (OS), and strategy success rate (SSR). Acute and late toxicity were evaluated. Results: Seventy patients were included from October 2014 to January 2019, and the most frequent primary diagnosis was non-small-cell lung cancer (N = 36, 51.4%). A total of 1174 BMs were treated at first treatment, corresponding to a median number of 14 BMs per patient. Most of the patients (N = 51, 72.6%) received a single fraction of 20–24 Gy. At 1 year, OS was 62.3%, with a median OS of 19.2 months, and SSR was 77.8%. A cumulative number of 1537 BM were treated over time, corresponding to a median cumulative number of 16 BM per patient. At 1-year, the LCR was 97.3%, with a cumulative incidence of radio-necrosis of 2.1% per lesion. Three patients (4.3%) presented Grade 2 toxicity, and there was no Grade ≥ 3 toxicity. The number of treated BMs and the treatment volume did not influence OS or SSR (p > 0.05). Conclusions: SRT was highly efficient in controlling the BM, with minimal side effects. In this setting, an SRT treatment should be proposed even in patients with ≥10 BMs at diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: In The Netherlands, it has been agreed to start the treatment of cancer patients within six weeks of their first visit to the outpatient clinic. But in 2020, the care for COVID-19 patients and staff shortages have led to less capacity for regular surgical care. In this study, we used a national registry to investigate the impact of the COVID-19 pandemic on the time to start of treatment for cancer patients undergoing surgery. We found that, despite pressure on the healthcare system, more surgical cancer patients started treatment within six weeks, compared to the years before the COVID-19 pandemic. This could be because cancer care was given priority over other types of surgery. However, during the pandemic, fewer patients underwent surgery for cancer then before the pandemic. These were particularly patients with early-stage tumours. They might have received other treatments or were diagnosed with cancer later on. To avoid delay in oncological treatment, a 6-weeks norm for time to treatment has been agreed on in The Netherlands. However, the impact of the COVID-19 pandemic on health systems resulted in reduced capacity for regular surgical care. In this study, we investigated the impact of the COVID-19 pandemic on time to treatment in surgical oncology in The Netherlands. Methods: A population-based analysis of data derived from five surgical audits, including patients who underwent surgery for lung cancer, colorectal cancer, upper gastro-intestinal, and hepato-pancreato-biliary (HPB) malignancies, was performed. The COVID-19 cohort of 2020 was compared to the historic cohorts of 2018 and 2019. Primary endpoints were time to treatment initiation and the proportion of patients whose treatment started within 6 weeks. The secondary objective was to evaluate the differences in characteristics and tumour stage distribution between patients treated before and during the COVID-19 pandemic. Results: A total of 14,567 surgical cancer patients were included in this study, of these 3292 treatments were started during the COVID-19 pandemic. The median time to treatment decreased during the pandemic (26 vs. 27 days, p < 0.001) and the proportion of patients whose treatment started within 6 weeks increased (76% vs. 73%, p < 0.001). In a multivariate logistic regression analysis, adjusting for patient characteristics, no significant difference in post-operative outcomes between patients who started treatment before or after 6 weeks was found. Overall, the number of procedures performed per week decreased by 8.1% during the pandemic. This reduction was most profound for patients with stage I lung carcinoma and colorectal carcinoma. There were fewer patients with pulmonary comorbidities in the pandemic cohort (11% vs. 13%, p = 0.003). Conclusions: Despite pressure on the capacity of the healthcare system during the COVID-19 pandemic, a larger proportion of surgical oncological patients started treatment within six weeks, possibly due to prioritisation of cancer care and reductions in elective procedures. However, during the pandemic, a decrease in the number of surgical oncological procedures performed in The Netherlands was observed, especially for patients with stage I disease. [ABSTRACT FROM AUTHOR]

Simple Summary: This study assessed hypo-fractionated radiotherapy's feasibility and acute toxicity using the first Spanish 0.35T MR-LINAC in 37 patients. Prostate tumors (59.46%) were the most treated, followed by pancreatic tumors (32.44%). Treatment adaptation was successful, with manageable acute toxicity profiles. For prostate cancer, hypo-fractionated radiotherapy yielded promising outcomes with minimal toxicity, predominantly grade I and II cystitis. Pancreatic cancer patients received ablative dose radiotherapy with acceptable toxicity. Quality assurance measures demonstrated precise dose delivery. Overall, our study highlights the safety and feasibility of hypo-fractionated radiotherapy on a 0.35T MR-LINAC, particularly for challenging anatomical sites like prostate and pancreatic tumors, supporting its potential as an effective cancer treatment strategy. This observational, descriptive, longitudinal, and prospective basket-type study (Registry #5289) prospectively evaluated the feasibility and acute toxicity of hypo-fractionated radiotherapy on the first 0.35T MR-LINAC in Spain. A total of 37 patients were included between August and December 2023, primarily with prostate tumors (59.46%), followed by pancreatic tumors (32.44%). Treatment regimens typically involved extreme hypo-fractionated radiotherapy, with precise dose delivery verified through quality assurance measures. Acute toxicity assessment at treatment completion revealed manageable cystitis, with one case persisting at the three-month follow-up. Gastrointestinal toxicity was minimal. For pancreatic tumors, daily adaptation of organ-at-risk (OAR) and gross tumor volume (GTV) was practiced, with median doses to OAR within acceptable limits. Three patients experienced gastrointestinal toxicity, mainly nausea. Overall, the study demonstrates the feasibility and safety of extreme hypo-fractionated radiotherapy on a 0.35T MR-LINAC, especially for challenging anatomical sites like prostate and pancreatic tumors. These findings support the feasibility of MR-LINAC-based radiotherapy in delivering precise treatments with minimal toxicity, highlighting its potential for optimizing cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Internet resources, both technical and informal, have become important aspects of developing E-Health applications for cancer populations. Despite extrinsic and intrinsic patient factors applicable to all patient populations, there exist patient population-specific aspects that E-Health developers and physicians should be aware of when introducing E-Health offers to specific cancer patient populations. A better understanding of specific aspects of the digitalization of gynecologic cancer patients will help to develop specific E-Health offers for this patient population. The influence of digitalization on information-seeking, decision-making properties of patients, therapy monitoring, and patient–physician interactions has and will change the global health sector tremendously. With this study, we add knowledge on the degree of digitalization, digital device availability, the use and availability of home and mobile internet access, and the willingness to use novel forms of patient–physician interactions in a group of gynecologic cancer patients. From July 2017 to March 2022, 150 women with a diagnosis of gynecologic malignancy at the University Hospital of Cologne participated in this questionnaire-based cohort study. Any one of three potential internet access devices (stationary computer, smartphone, or tablet) is owned by 94% of patients and the only patient intrinsic factor that is significantly associated with the property of any one of these internet access devices is age. The Internet is used daily or several times per week to assess information on their disease by 92.8%, 90.1% use the Internet for communicational purposes and 71.9% and 93.6% are willing to communicate with their treating physicians via E-Mail or even novel forms of communication, respectively. In conclusion, the predominant majority of gynecologic cancer patients can be reached by modern internet-based E-Health technologies. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study aimed to delineate the variables associated with the link between chronic periodontitis and hematologic cancers. The hazard ratio for hematologic cancers in patients with chronic periodontitis was also evaluated. Comprehensive statistical analyses revealed a 1.25-fold risk of hematologic cancers in the chronic periodontitis group. Factors such as being male and having hypertension were identified as increased risk factors for hematologic cancers. This nuanced exploration, including a subtype analysis for leukemia and lymphoma, contributes valuable insights into the complex relationship between chronic periodontitis and specific hematologic cancer subtypes. These findings could enhance our understanding of potential cancer risk factors in Taiwan. Background: Chronic periodontitis, an inflammation-related disorder affecting global populations, has been revealed to be linked to diverse cancers. Numerous epidemiological studies have not shown a link between chronic periodontitis and blood cancers in Taiwan. Methods: This study included 601,628 patients, diagnosed with newly chronic periodontitis by the ICD-9-CM classification, who were enrolled from 2001 to 2021 in the National Health Insurance Research Database (NHIRD) in Taiwan. In this study, we employed comprehensive statistical analyses to investigate the association between chronic periodontitis and hematologic cancers. Initially, we calculated incidence density and used a Poisson regression to analyze relative risk. Subsequently, we compared the cumulative incidence of hematological cancer in both chronic and non-chronic periodontitis groups using the Kaplan–Meier method. Results: The results revealed a significantly lower cumulative incidence of hematologic cancer in individuals with non-chronic periodontitis over a 12-year follow-up period. To further explore the risk factors, a Cox proportional hazard regression analysis was conducted. Being male (adjusted hazard ratio [aHR] = 1.21, 95% CI: 1.04 to 1.42; p = 0.014) and having hypertension (aHR = 1.34, 95% CI: 1.06 to 1.69; p = 0.015) were demonstrated to be associated with an increased risk of hematologic cancers, respectively. In addition, in a subtype multivariate analysis for categorizing hematologic cancers into lymphoma and leukemia, the aHR for leukemia was 1.48 (95% CI: 1.13 to 1.93; p = 0.004) and aHR for lymphoma was 1.15 (95% CI: 0.96 to 1.37; p = 0.140). Conclusions: This study found that being male and having hypertension were the significant risk factors for hematological malignancies. Moreover, the association between chronic periodontitis and specific subtypes of hematologic cancers was confirmed. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastases from Hepatopancreaticobiliary (HPB) cancers are extremely rare and indicate a very poor prognosis. Patients with HPB cancers often have several months of life expectancy from the diagnosis of the brain metastases. Due to the rarity, there is no established protocol on how to treat brain metastases from HPB malignancies. Stereotactic radiosurgery provides the advantage of out-patient noninvasive management of brain metastases. We aim to retrospectively review the post-SRS outcomes of HPB patients with brain metastases in search for the optimal radiation delivery dose for HPB brain metastases. Our study showed that SRS could achieve a 94.7% local tumor control rate per tumor and newly developed brain metastases could be treated with repeat SRS. The favorable outcome of the present study indicates that SRS is effective in controlling HPB brain metastases and is instrumental in preserving patients' quality of life. Background: The role of stereotactic radiosurgery (SRS) for patients with brain metastases from hepatopancreaticobiliary (HPB) cancers has yet to be established. The authors present a single-institution experience of patients with HPB cancers who underwent SRS when their cancer spread to the brain. Methods: We surveyed our Gamma Knife SRS data base of 18,000 patients for the years 1987–2022. In total, 19 metastatic HPB cancer patients (13 male) with 76 brain metastases were identified. The median age at SRS was 61 years (range: 48–83). The primary cancer sites were hepatocellular carcinoma (HCC, 11 patients), cholangiocarcinoma (CCC, 2 patients), and pancreatic carcinoma (PCC, 6 patients). The median Karnofsky Performance Score (KPS) was 80 (range: 50–90). Two patients underwent pre-SRS whole-brain fractionated radiation therapy (WBRT) and eight patients underwent pre-SRS surgical resection. All SRS was delivered in single session. The median margin dose was 18 Gy (range: 15–20). The median cumulative tumor volume was 8.1 cc (range: 1.0–44.2). Results: The median patient overall survival (OS) after SRS was 7 months (range 1–79 months). Four patients had documented local tumor progression after SRS at a median time of 8.5 months (range: 2–15) between SRS and progression. Out of 76 treated tumors, 72 tumors exhibited local control. The local tumor control rate per patient was 78.9%. The local tumor control per tumor was 94.7%. Four patients developed new brain metastases at a median of 6.5 months (range: 2–17) after SRS. No patient experienced adverse radiation effects (AREs). At the last follow-up, 18 patients had died, all from systemic disease progression. Conclusions: Metastatic spread to the brain from HPB cancers occurs late in the course of the primary disease. In this study, all deceased patients ultimately died from primary disease progression. SRS is a non-invasive strategy that maximally preserves quality of life, and our results reported favorable outcomes compared to the existing literature. SRS should be considered as one of the primary management strategies for patients with brain metastatic spread from HPB cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Checkpoint-inhibitor-associated diabetes mellitus is a severely morbid immune-related adverse event that occurs from immunotherapy treatment during cancer therapy. Many patients and clinicians opt to discontinue therapy after this adverse event occurs while others choose to resume treatment. There are currently no data to inform this decision in terms of risks and benefits to the patient. This study aims to determine future risk for immune-related adverse events and cancer outcomes in patients who make this decision after experiencing diabetes mellitus. Immune checkpoint inhibitor (CPI)-induced diabetes mellitus (CPI-DM) is a rare immune-related adverse event (irAE). Patients and providers fear that continuing CPIs puts patients at risk for additional irAEs and thus may discontinue therapy. Currently, there are little data to inform this decision. Therefore, this study aims to elucidate whether discontinuing CPIs after diagnosis of CPI-DM impacts the development of future irAEs and cancer outcomes such as progression and death. Patients who developed CPI-DM during cancer treatment at UCSF from 1 July 2015 to 5 July 2023 were analyzed for cancer outcomes and irAE development. Fisher's exact tests, Student t-tests, Kaplan–Meier methods, and Cox regression were used as appropriate. Of the 43 patients with CPI-DM, 20 (47%) resumed CPIs within 90 days of the irAE, 4 (9%) patients restarted after 90 days, and 19 (44%) patients never restarted. Subsequent irAEs were diagnosed in 9 of 24 (38%) who resumed CPIs and 3 of 19 (16%) who discontinued CPIs (p = 0.17). There was no significant difference in death (p = 0.74) or cancer progression (p = 0.55) between these two groups. While our single-institution study did not show worse cancer outcomes after discontinuing CPIs, many variables can impact outcomes, which our study was not adequately powered to evaluate. A nuanced approach is needed to decide whether to continue CPI treatment after a severe irAE like CPI-DM. [ABSTRACT FROM AUTHOR]

Simple Summary: Metabolic reprogramming in HER2-positive breast cancer is associated with acquired resistance to targeted therapies. Thus, targeting dysregulated metabolic pathways in cancers is highly beneficial. In this study, we examined the anti-tumor effects of an LXR inverse agonist GAC0001E5 (1E5) in HER2-positive breast cancer in vitro. Strikingly, we observed disruption of two major pathways, glutaminolysis and de novo lipogenesis, leading to oxidative stress and cell death. Additionally, we discovered the indirect effects of 1E5 in downregulating HER2 expression through fatty acid synthase (FASN). Moreover, in combinatory treatments of 1E5 and lapatinib, 1E5 potentiates lapatinib's effects. These findings indicate the importance of 1E5 as a metabolic disruptor in HER2-positive breast cancer. The HER2-positive subtype accounts for approximately one-fifth of all breast cancers. Insensitivity and development of acquired resistance to targeted therapies in some patients contribute to their poor prognosis. HER2 overexpression is associated with metabolic reprogramming, facilitating cancer cell growth and survival. Novel liver X receptor (LXR) ligand GAC0001E5 (1E5) has been shown to inhibit cancer cell proliferation by disrupting glutaminolysis and inducing oxidative stress. In this study, HER2-positive breast cancer cells were treated with 1E5 to determine their potential inhibitory effects and mechanisms of action in HER2-positive breast cancers. Similar to previous observations in other cancer types, 1E5 treatments inhibited LXR activity, expression, and cancer cell proliferation. Expression of fatty acid synthesis genes, including fatty acid synthase (FASN), was downregulated following 1E5 treatment, and results from co-treatment experiments with an FASN inhibitor suggest that the same pathway is targeted by 1E5. Treatments with 1E5 disrupted glutaminolysis and resulted in increased oxidative stress. Strikingly, HER2 transcript and protein levels were both significantly downregulated by 1E5. Taken together, these findings indicate the therapeutic potential of targeting HER2 overexpression and associated metabolic reprogramming via the modulation of LXR in HER2-positive breast cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Superficial bladder cancer is a common disease. The standard method for treatment is a transurethral resection of bladder tumour (TURBT). This is a surgery under general anaesthesia with a complication rate of up to 26%, and it is potentially associated with severe side effects. A newer method, transurethral laser ablation (TULA), is a less invasive procedure performed under local anaesthesia and with a lower risk of complications. We aimed to compare these different transurethral procedures in the treatment of bladder tumours to evaluate any clinically relevant differences in symptoms and side effects. We used questionnaires regarding urinary symptoms, postoperative side effects, and quality of life. We showed that patients undergoing TURBT reported a more extensive early symptom burden and had a higher need for contacting the healthcare system compared to TULA-treated patients. If some TURBTs can be replaced with TULA, it will be beneficial for both future patients and the healthcare system. The standard procedure for diagnosis and treatment of bladder tumours, transurethral resection of bladder tumour (TURBT), is associated with a complication rate of up to 26% and potentially has severe influence on patient-reported outcomes (PRO). Outpatient transurethral laser ablation (TULA) is an emerging new modality that is less invasive with a lower risk of complications and, thereby, possibly enhanced PRO. We collected PRO following transurethral procedures in treatment of bladder tumours to evaluate any clinically relevant differences in symptoms and side effects. This prospective observational study recruited consecutive patients undergoing different bladder tumour-related transurethral procedures. Patients filled out questionnaires regarding urinary symptoms (ICIQ-LUTS), postoperative side effects, and quality of life (EQ-5D-3L) at days 1 and 14 postoperatively. In total, 108 patients participated. The most frequently reported outcomes were postoperative haematuria and pain. Patients undergoing TURBT reported longer lasting haematuria, a higher perception of pain, and a more negative impact on quality of life compared to patients undergoing TULA. TURBT-treated patients had more cases of acute urinary retention and a higher need for contacting the healthcare system. Side effects following transurethral procedures were common but generally not severe. The early symptom burden following TURBT was more extensive than that following TULA. [ABSTRACT FROM AUTHOR]

Simple Summary: This is a retrospective national cohort study that aims to assess the risk of developing pancreatic cancer in patients with type 2 diabetes mellitus (T2DM) who are being treated with Glucagon-like Peptide-1 receptor agonists. We exclude patients with multiple risk factors for pancreatic cancer from our study. We retrospectively follow the patients for 7 years after the initiation of treatment. Current evidence is controversial about their use and the possible risk of pancreatic disease. We aim to revoke the association of pancreatic cancer with their use in support of their continued use due to their beneficial cardiovascular and renal effects. Background: GLP-1 RAs are widely used for T2DM treatment due to their cardiorenal and metabolic benefits. This study examines the risk of pancreatic cancer with GLP-1 RA use in patients with T2DM. Methods: We analyzed TriNetX's deidentified research database using the U.S. Collaborative Network comprising 62 healthcare organizations across the U.S.A. Patients with T2DM were split into two cohorts: one receiving GLP-1 RAs, and one not receiving GLP-1 RAs. We excluded patients with known risk factors for pancreatic cancer, including pancreatic cysts, a personal or family history of BRCA1, BRCA2, CDKN2A, KRAS, MEN1, MLH1, MSH2, NOTCH1, PALB2, PMS2, and PRSS1S genes, family history of pancreatic cancer, and VHL syndrome. Using a 1:1 propensity score-matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then compared the rate of pancreatic cancer between the two cohorts at a 7-year interval. Results: Out of 7,146,015 identified patients with T2DM, 10.3% were on a GLP-1 RA and 89.7% were not. Post-PSM, 721,110 patients were in each group. Patients on GLP-1 RAs had a 0.1% risk compared to a 0.2% risk of pancreatic cancer in the 7-year timeframe. Conclusion: The use of GLP-1 RAs in patients with type 2 diabetes mellitus (T2DM) does not appear to substantially elevate the risk of pancreatic cancer; in fact, it may potentially exert a protective effect. [ABSTRACT FROM AUTHOR]

Simple Summary: The triage of glandular cell abnormalities of the uterine cervix poses many challenges due to high interobserver variability. p16/Ki67 dual staining has been proposed as an objective test that could decrease interobserver variability in diagnosing atypical glandular cells. Our results indicate the possible role of p17/Ki67 dual staining in triaging glandular cell abnormalities. Very limited information exists about the role of p16/Ki67 dual staining on glandular cells in detecting glandular precancerous lesions and cervical adenocarcinoma. In this study, we investigated the diagnostic accuracy of p16/Ki67 dual staining for the detection of glandular and squamous lesions on the uterine cervix and for cancer of the upper reproductive tract. We performed a retrospective analysis of prospectively collected data on 96 patients with glandular cell abnormalities. We analyzed the diagnostic accuracy of p16/Ki67 dual staining for atypical glandular cells, not otherwise specified (AGC-NOS); atypical glandular cells, favor neoplastic (AGC-FN); adenocarcinoma in situ (AIS); and A-CA (cervical adenocarcinoma). A separate analysis for the detection of squamous precancerous lesions and squamous-cell carcinoma (CIN3+) and for cancer of the upper reproductive tract (EC/OC) was performed. Among patients who had normal histology or a low-grade lesion on final analysis, only 8.5% had positive dual staining. On the other hand, 85.7% of patients with AIS+ on final histology had positive dual staining. The respective specificities of p16/Ki67 dual staining on AGC-NOS for the detection of AIS+ (adenocarcinoma in situ or cervical adenocarcinoma), CIN3+ and EC/OC were 91.5%, 88.7% and 86.4%. High specificity values of p16/Ki67 dual staining on cervical smears labelled as AGC-NOS for the detection of CIN3+ and AIS+ suggest that this method might be a useful addition in cervical cancer screening. [ABSTRACT FROM AUTHOR]

Simple Summary: Although cancer survival is increasing and many survivors report having to endure pain, its prevalence and consequences have received little attention. We found that pain is associated with reduced quality of life as well as diminished emotional and professional performance in long-term cancer survivors. In addition, a neuropathic component often goes underdiagnosed and/or undertreated. Adopting appropriate neuropathic pain diagnostic tools should be standard clinical practice and targeting the neuropathic component seems to be a good, yet underused therapeutic approach which has the potential to improve cancer survivors' health outcomes. Cancer survival is becoming more common which means that there is now a growing population of cancer survivors, in whom pain may be common. However, its prevalence has hardly been addressed systematically. We aimed to assess the prevalence and explore the pathophysiology and impact of pain on health outcomes in cancer survivors. We conducted a retrospective–prospective cohort study in cancer-free patients diagnosed with cancer at least five years before the study start date. We used multivariable regression to establish the association of patients' cancer characteristics with pain, and then the association of patients' pain features with health outcomes and related symptoms. Between March and July 2021, 278 long-term cancer survivors were evaluated. Almost half of them (130/278, 46.8%) had pain, of whom 58.9% had a probable neuropathic component, but only 18 (13.8%) were taking specific drugs for neuropathic pain. A history of surgery-related pain syndrome in breast cancer patients was more than twice as frequent in the pain cohort. Post-chemotherapy and post-radiotherapy pain syndromes were uncommon. Pain was associated with lower QoL, emotional functioning, professional performance, and disability scores. Pain is a frequent health determinant in cancer survivors. Referral to specialised pain services may be a reasonable move in some cases. [ABSTRACT FROM AUTHOR]

Simple Summary: Though diagnosed earlier, Hispanic patients with high-grade glioma experience longer survival intervals. As environmental or biologic factors are thought to influence prognosis, the aim of our retrospective study was to determine if this improvement in disease course still occurs in a socioeconomically disadvantaged sample of Hispanic patients (an environmental condition pre-disposing patients to poor oncologic outcomes). We found that despite significantly higher social vulnerability, Hispanic patients experienced an additional 14 months before the first tumor recurrence compared to non-Hispanic patients. Specifically, in those with aggressive glioblastomas, Hispanic ethnicity independently predicted an additional 8.5 months before recurrence in a multivariate analysis. These findings emphasize the need for basic science investigations into the biologic mechanisms potentially explaining Hispanic ethnicity's influence on high-grade glioma outcomes. High-grade gliomas (HGGs; WHO grade III or IV) are the most common and lethal brain malignancy. Patients of Hispanic ethnicity are diagnosed with HGGs earlier than non-Hispanic patients, but they exhibit improved HGG survival following diagnosis. Either environmental or biological factors could explain this survival benefit. We aimed to determine if post-diagnosis advantages would still be present in Hispanic patients with high social vulnerability, an environmental condition predisposing patients to poor oncologic outcomes. HGG outcomes were retrospectively assessed in a cohort of 22 Hispanic patients and 33 non-Hispanic patients treated for HGGs from 2015 to 2020 at a single institution that serves a highly vulnerable region. Compared to non-Hispanic patients, Hispanic patients demonstrated higher social vulnerability index scores (96.8 + 0.7 vs. 76.3 + 4.6; *** p = 0.0002) and a 14-month longer interval between diagnosis and recurrence (19.7 + 5.9 (n = 13) vs. 5.5 + 0.6 months (n = 19); ** p = 0.001). In only those patients with more aggressive IDH-1 wildtype tumors (glioblastoma), Hispanic ethnicity still related to a longer time before recurrence (15.8 + 5.9 months (n = 9); 5.5 + 0.6 months (n = 18); * p = 0.034), and in a multivariate analysis, Hispanic ethnicity predicted time-to-recurrence (* p = 0.027) independent of patient age, functional status, MGMT gene methylation, or treatments received. Therefore, environmental factors, specifically social vulnerability, did not obscure the post-diagnosis benefits associated with Hispanic ethnicity. In future experiments, basic studies should be prioritized which investigate the cellular or genetic mechanisms underlying this ethnicity effect on HGG progression in the hopes of improving care for these devastating malignancies. [ABSTRACT FROM AUTHOR]

Simple Summary: Identifying the genetic cause of a retinoblastoma tumour can help doctors determine any future cancer risk for the patient or their family. Somatic testing has historically used DNA from the tumour, after the eye has been removed. We and others have previously shown cell-free DNA (cfDNA) from the tumour is present in the eye fluid of retinoblastoma patients. In this study we tested eye fluid from 68 patients, collected at different points in their treatment. Measurable levels of cfDNA were found in all 11 samples of eye fluid taken from patients who had received less than three cycles of chemotherapy, and 95% (21/22) of causal genetic variants were identified. Eye fluid collected later in the treatment had 150 times less cfDNA and only 46% of genetic variants (25/54) could be detected. Eye fluid sampling early in treatment is therefore likely to be required for successful somatic testing in retinoblastoma patients undergoing eye conservation treatment. The identification of somatic RB1 variation is crucial to confirm the heritability of retinoblastoma. We and others have previously shown that, when tumour DNA is unavailable, cell-free DNA (cfDNA) derived from aqueous humour (AH) can be used to identify somatic RB1 pathogenic variation. Here we report RB1 pathogenic variant detection, as well as cfDNA concentration in an extended cohort of 75 AH samples from 68 patients. We show cfDNA concentration is highly variable and significantly correlated with the collection point of the AH. Cell-free DNA concentrations above 5 pg/µL enabled the detection of 93% of known or expected RB1 pathogenic variants. In AH samples collected during intravitreal chemotherapy treatment (Tx), the yield of cfDNA above 5 pg/µL and subsequent variant detection was low (≤46%). However, AH collected by an anterior chamber tap after one to three cycles of primary chemotherapy (Dx1+) enabled the detection of 75% of expected pathogenic variants. Further limiting our analysis to Dx1+ samples taken after ≤2 cycles (Dx ≤ 2) provided measurable levels of cfDNA in all cases, and a subsequent variant detection rate of 95%. Early AH sampling is therefore likely to be important in maximising cfDNA concentration and the subsequent detection of somatic RB1 pathogenic variants in retinoblastoma patients undergoing conservative treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: We studied the feasibility and safety of using bronchoscopically implanted electromagnetic transponders to monitor deep inspiration breath hold (DIBH) for thoracic radiation therapy (RT) of primary lung cancers or lung metastases. Three transponders were implanted near the tumor, followed by CT simulation. The initial gating window was ±5 mm; in a second cohort, the window was incrementally reduced to determine the smallest feasible gating window: this was identified to be ±3 mm. Among the 48 patients enrolled, transponder-guided DIBH was feasible in all but two patients (96% feasible), where it failed because the distance between the transponders and the antenna was >19 cm. Toxicities at least possibly related to transponders or the implantation procedure were grade 2 in six patients, grade 3 in three patients, and grade 4 in one patient. Toxicities at least possibly related to RT were grade 2 in 18 patients and grade 3 in four patients. Transponder-guided DIBH is a feasible and safe approach for delivering thoracic RT. Background: Electromagnetic transponders bronchoscopically implanted near the tumor can be used to monitor deep inspiration breath hold (DIBH) for thoracic radiation therapy (RT). The feasibility and safety of this approach require further study. Methods: We enrolled patients with primary lung cancer or lung metastases. Three transponders were implanted near the tumor, followed by simulation with DIBH, free breathing, and 4D-CT as backup. The initial gating window for treatment was ±5 mm; in a second cohort, the window was incrementally reduced to determine the smallest feasible gating window. The primary endpoint was feasibility, defined as completion of RT using transponder-guided DIBH. Patients were followed for assessment of transponder- and RT-related toxicity. Results: We enrolled 48 patients (35 with primary lung cancer and 13 with lung metastases). The median distance of transponders to tumor was 1.6 cm (IQR 0.6–2.8 cm). RT delivery ranged from 3 to 35 fractions. Transponder-guided DIBH was feasible in all but two patients (96% feasible), where it failed because the distance between the transponders and the antenna was >19 cm. Among the remaining 46 patients, 6 were treated prone to keep the transponders within 19 cm of the antenna, and 40 were treated supine. The smallest feasible gating window was identified as ±3 mm. Thirty-nine (85%) patients completed one year of follow-up. Toxicities at least possibly related to transponders or the implantation procedure were grade 2 in six patients (six incidences, cough and hemoptysis), grade 3 in three patients (five incidences, cough, dyspnea, pneumonia, and supraventricular tachycardia), and grade 4 pneumonia in one patient (occurring a few days after implantation but recovered fully and completed RT). Toxicities at least possibly related to RT were grade 2 in 18 patients (41 incidences, most commonly cough, fatigue, and pneumonitis) and grade 3 in four patients (seven incidences, most commonly pneumonia), and no patients had grade 4 or higher toxicity. Conclusions: Bronchoscopically implanted electromagnetic transponder–guided DIBH lung RT is feasible and safe, allowing for precise tumor targeting and reduced normal tissue exposure. Transponder–antenna distance was the most common challenge due to a limited antenna range, which could sometimes be circumvented by prone positioning. [ABSTRACT FROM AUTHOR]