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Simple Summary: Immune checkpoint inhibitors (ICIs) are a common and growing type of cancer treatment, but they can cause side effects. This study aims to understand these side effects in patients with kidney cancer and bladder cancer. We compared the types and severity of side effects between these two groups to determine if there are differences. We also compared them to other tumor types to see if there is a unique pattern. The findings will help doctors better predict and manage side effects. This will hopefully lead to improving patient care for those receiving ICI treatment. Background: Immune checkpoint inhibitors (ICIs) have become common lines of therapy for genitourinary cancers (GUcs). Given their widespread use, understanding the risk factors, comparative profiles, and timing of immune-related adverse events (irAEs) is essential. Methods: We created an IRB-approved retrospective registry of all patients who received at least one dose of an ICI for any indication between 1 February 2011 and 7 April 2022 at a comprehensive cancer center and its outreach clinics. Dichotomous outcomes were modeled using multivariable logistic regression. Survival outcomes were compared using multivariable Cox regression. Results: Among 3101 patients, 196 had renal cell carcinoma (RCC) and 170 had urothelial tumors. RCC patients were more likely to experience irAEs (OR 1.78; 95% CI 1.32–2.39), whereas urothelial carcinoma patients were not (OR 1.22; 95% CI 0.88–1.67). RCC patients were more prone to dermatitis, thyroiditis, acute kidney injury, and myocarditis, compared to other tumors, while urothelial carcinoma patients were not. The impact of irAEs on survival was not significantly different for GUcs compared to other tumors. Conclusions: RCC primaries have a significantly different irAE profile than most tumors, as opposed to urothelial primaries. Further, RCC was more likely to experience any irAEs. Heterogeneity of survival benefits by irAEs was not seen. [ABSTRACT FROM AUTHOR]

Simple Summary: Women treated for cervical precancers (CIN2/3) have an increased risk for recurrent lesions and therefore require post-treatment monitoring. Standard follow-up care based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. Host cell methylation correlates highly with CIN2/3 and may thus be a more suitable marker than hrHPV, particularly since HPV infection is not confined to women with the disease. Here, we show that in combination with cytology, the methylation markers comprising GynTect® are as sensitive as hrHPV for the detection of recurrent CIN2/3 lesions but are more specific. A reduction in the rate of false positive results would not only be more cost-effective but may also reduce the number of women requiring re-treatment. These findings must be verified in a sufficiently large validation study. Post-treatment follow-up in women with CIN3 is mandatory due to relapse in up to 15% of patients within 2 years. Standard follow-up care based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. The aim of our proof-of-concept case-control study was to evaluate the performance of the methylation test GynTect® for the detection of recurrent CIN2/3 during follow-up. Residual clinical material from a recent, prospective, multicenter, observational study was available for further analysis. We studied a sample of 17 cases with recurrent CIN2/3 diagnosed within 24 months of follow-up and 31 controls without recurrence. DNA from cervical scrapes at baseline (immediately before CIN3 surgery) and up to three follow-up visits were analyzed for hrHPV and GynTect® methylation status. Cytology data were available from the previous study. Overall, 12 cases and 21 controls were GynTect-positive at baseline. In these subgroups, single test sensitivity at first follow-up was 67% (95% CI 39–87%) for GynTect® compared to 83% (95% CI 55–96%) for hrHPV (p = 0.50). Single test specificity was significantly higher for GynTect® (90%, 95% CI 71–98% vs. 62%, 95% CI 40–80%) (p = 0.03). In a co-testing setting, both hrHPV/cytology and GynTect®/cytology detected all recurrences. Specificity for GynTect®/cytology was higher than for hrHPV/cytology, but this difference was not statistically significant. In conclusion, for initially GynTect-positive patients, both hrHPV and GynTect® tests detected recurrent disease with similar sensitivity, but the GynTect® assay has a higher specificity. Incident hrHPV infection and/or persisting multifocal hrHPV infections without clinical disease are most likely responsible for the poorer specificity of the hrHPV test. A future prospective validation study will have to show whether GynTect®/cytology co-testing can outperform hrHPV/cytology co-testing in post-treatment surveillance. [ABSTRACT FROM AUTHOR]

Simple Summary: In metastatic estrogen-receptor (ER)-positive HER2-negative breast cancer, resistance to endocrine therapy can be caused by ER loss and the mutation of ESR1, the gene coding for ERs. These mechanisms have been studied in isolation but not in the same population. Here, we studied both mechanisms and their interaction. We found that, in a population of 136 patients, one of these mechanisms was responsible for endocrine resistance in 30% of the patients. ESR1 mutation was associated with endocrine therapy. ER loss and ESR1 mutation were mutually exclusive, so testing for ESR1 mutations can be limited to ER-positive metastases. Furthermore, we demonstrated that ER loss has a negative effect on overall survival, while we did not observe this effect for ESR1 mutation. In patients with metastatic estrogen-receptor (ER)-positive HER2-negative breast cancer, the loss of ER expression and the mutation of ESR1—the gene encoding the ER receptor—are mechanisms for resistance to endocrine therapy. We aimed to determine the frequency of these mechanisms and their interaction. Metastases were retrieved from our pathology files. ESR1 hotspot mutations resulting in p.(D538G), p.(Y537S), and p.(L536H) were determined by means of pyrosequencing. Clinical data were retrieved from electronic medical records. A total of 136 metastases were available for analysis. ER loss was found in 23 metastases (17%). ESR1 mutations were found in 18 metastases (13%), including p.(D538G) in 9, p.(Y537S) in 7, and p.(L536H) in 2. ESR1 mutation and ER loss were mutually exclusive (p = 0.042), and ESR1 mutation was associated with endocrine therapy (p = 0.002). ESR1 mutation was found in two primary breast cancers. ESR1 mutations are rare in primary breast cancer and develop in metastases during endocrine therapy. Furthermore, ER loss had a statistically significant negative effect on overall survival when compared to patients without ER loss, with a rate ratio of 3.21 (confidence interval 1.95–5.26). No such effect was observed for ESR1 mutations, with a rate ratio of 1.15 (confidence interval 0.67–1.95). We conclude that ER loss and ESR1 mutation together account for 30% of the resistance to endocrine therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Survivors of childhood cancer are predisposed to a range of late effects of treatment, including high symptom burden. Symptom burden may vary over time. The aim of this prospective pilot study was to assess the feasibility of collecting daily symptoms from adult survivors of childhood cancer using mobile health (mHealth) technology to evaluate symptom fluctuation and associations with future health-related quality of life (HRQOL). The 41 survivors included in this study had high adherence to symptom reporting (83%) and HRQOL reporting (95%). Variability of daily symptom burden differed from person-to-person (74%), day-to-day (18%), and month-to-month (8%). Additionally, a higher symptom burden was associated with poorer HRQOL in the future. Daily assessment of symptoms using mHealth technology revealed fluctuations in symptomology and the association between symptom burden and HRQOL. This method of symptom assessment is valuable for improving our understanding of symptom dynamics and sources of variability. Background: Cancer therapies predispose survivors to a high symptom burden. This study utilized mobile health (mHealth) technology to assess the feasibility of collecting daily symptoms from adult survivors of childhood cancer to evaluate symptom fluctuation and associations with future health-related quality-of-life (HRQOL). Methods: This prospective study used an mHealth platform to distribute a 20-item cancer-related symptom survey (5 consecutive days each month) and an HRQOL survey (the day after the symptom survey) over 3 consecutive months to participants from the Childhood Cancer Survivor Study. These surveys comprised a PROMIS-29 Profile and Neuro-QOL assessed HRQOL. Daily symptom burden was calculated by summing the severity (mild, moderate, or severe) of 20 symptoms. Univariate linear mixed-effects models were used to analyze total, person-to-person, day-to-day, and month-to-month variability for the burden of 20 individual symptoms. Multivariable linear regression was used to analyze the association between daily symptom burden in the first month and HRQOL in the third month, adjusted for covariates. Results: Out of the 60 survivors invited, 41 participated in this study (68% enrollment rate); 83% reported their symptoms ≥3 times and 95% reported HRQOL in each study week across 3 months. Variability of daily symptom burden differed from person-to-person (74%), day-to-day (18%), and month-to-month (8%). Higher first-month symptom burden was associated with poorer HRQOL related to anxiety (regression coefficient: 6.56; 95% CI: 4.10–9.02), depression (6.32; 95% CI: 3.18–9.47), fatigue (7.93; 95% CI: 5.11–10.80), sleep (6.07; 95% CI: 3.43–8.70), pain (5.16; 95% CI: 2.11–8.22), and cognitive function (–6.89; 95% CI: –10.00 to –3.79) in the third month. Conclusions: Daily assessment revealed fluctuations in symptomology, and higher symptom burden was associated with poorer HRQOL in the future. Utilizing mHealth technology for daily symptom assessment improves our understanding of symptom dynamics and sources of variability. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiotherapy is the main local treatment for head and neck cancer. Radiation oncologists and patients should be alert to late carotid artery stenosis and brain necrosis after treatment. Objective: This study aims to examine whether radiation therapy doses are related to incidences of carotid artery stenosis and brain necrosis in a large-scale real-world database. Methods: We identified a cohort of HNC patients from the catastrophic illness patient dataset using ICD-9 or ICD-10 to compare the incidence and risks of carotid artery stenosis (CAS) and brain necrosis (RIBN) in patients who received a radiation therapy dose of ≥5400 cGy/30 fractions (group A) with those who received a radiation therapy dose of <5400 cGy/30 fractions (group B). The incidence and hazard ratios were quantified using Cox proportional hazards models. Results: A total of 19,964 patients were identified in group A and group B. Among them, 965 and 863 cases of CAS and 435 and 359 cases of RIBN were identified in group A and group B, respectively. There was no statistically significant association between the two groups for CAS risk, whereas there was a statistically significant association between the two groups for RIBN risk. The most common primary site of head and neck cancers was the nasopharynx (1144 of 19,964, 5.73%). Conclusions: Our study suggests that RT may increase the risk of carotid stenosis and brain necrosis in patients with NPC. To ensure patient safety during treatment, the optimal balance between tumor control and toxicity prevention in individual patients through minimization of the radiation dose to all relevant OARs must be properly understood. [ABSTRACT FROM AUTHOR]

Simple Summary: Studies analyzing specific treatment-related prognostic factors can provide important information about disease biology and improve the use of biomarkers to optimize treatment decisions. The aim of our retrospective study was to determine the prognostic performance of clinicopathological factors and blood biomarkers in patients with unresectable metastatic melanoma treated with BRAF and MEK inhibitors. A total of 199 patients were included in the multivariate analysis of the risk of progression and death. We found that primary tumor localization on the limbs, Clark invasion level V, M1c stage or M1d stage at the start of therapy, and elevated baseline serum S100B level were independently and significantly associated with poor outcomes. The present study suggests that clinicopathological factors, including primary tumor characteristics and stage of metastatic disease, as well as serum markers may provide information on the probability of survival in patients with advanced melanoma treated with BRAF and MEK inhibitors. Prognostic studies can provide important information about disease biology and improve the use of biomarkers to optimize treatment decisions. Methods: A total of 199 patients with advanced melanoma treated with BRAF + MEK inhibitors were included in our single-center retrospective study. We analyzed the risk of progression and death using multivariate Cox proportional hazard models. The predictive effect of prognostic factors on progression-free survival (PFS) was evaluated in ROC analysis. Results: We found that primary tumor localization, Clark level, pT category, baseline M stage and baseline serum S100B are independent and significant prognostic factors for PFS. The discriminative power of the combination of these factors was excellent for predicting 18 month PFS (AUC 0.822 [95% CI 0.727; 0.916], p < 0.001). Primary tumor localization on the extremities, Clark level V, baseline M1c stage or M1d stage, and elevated baseline serum S100B and LDH levels were independently and significantly associated with unfavorable overall survival (OS). Conclusion: Baseline M stage and serum S100B appear to be independent prognostic factors for both PFS and OS in melanoma patients treated with BRAF + MEK inhibitors. We newly identified significant and independent prognostic effects of primary tumor localization and Clark level on survival that warrant further investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: It is unknown whether different types of exercise effect physical function, quality of life, mental wellbeing, and symptoms in older patients with blood cancers. No studies specifically focusing on patients over 65 years were identified. However, across adult age groups, we found that exercise has small to moderate positive effects on physical function, aerobic capacity, muscle strength, quality of life, fatigue, pain, anxiety, and depression. These benefits were generally consistent regardless of age, except for physical function and pain, which favored younger adults. Overall, exercise improves physical function and quality of life and reduces symptoms in adults with blood cancers undergoing treatment, but the role of age remains uncertain. Older patients receiving antineoplastic treatment face challenges such as frailty and reduced physical capacity and function. This systematic review and meta-analysis aimed to evaluate the effects of exercise interventions on physical function outcomes, health-related quality of life (QoL), and symptom burden in older patients above 65 years with hematological malignancies undergoing antineoplastic treatment. This review adheres to Cochrane guidelines, with the literature searches last updated on 27 March 2024, including studies with patients above 18 years. Screening of identified studies, data extraction, risk of bias, and GRADE assessments were performed independently by two authors. Meta-analyses evaluated the impact of exercise, considering advancing age. Forty-nine studies contributed data to the meta-analyses. Five studies included patients with a mean age above 60 years, and none included only patients above 60. Exercise interventions had moderate to small positive effects on QoL global (SMD 0.34, 95% CI [0.04–0.64]) and physical function (SMD 0.29, 95% CI [0.12–0.45]). Age did not explain the variability in exercise effects, except for physical function (slope 0.0401, 95% CI [0.0118–0.0683]) and pain (slope 0.0472, 95% CI [0.01–0.09]), which favored younger patients. Exercise interventions improve physical function and QoL and reduce symptoms in adults with hematological malignancies undergoing antineoplastic treatment; however, the influence of age remains inconclusive. [ABSTRACT FROM AUTHOR]

Simple Summary: Obesity is a clear risk factor for future colorectal cancer (CRC), but its impact on mortality remains to be fully elucidated. Prior studies have had methodologic limitations, and key variables remain under-investigated. In this study of prospectively collected data from the Multiethnic Cohort, pre-diagnosis BMI trajectories were not associated with CRC-specific or all-cause mortality. Factors associated with mortality included African American race or Hawaiian ethnicity, smoking, and diabetes. Accounting for long-term BMI trajectories before diagnosis and other relevant factors demonstrates that obesity is not protective of mortality after CRC diagnosis. Background: Prior studies are inconclusive regarding the effect of obesity on mortality in persons with colorectal cancer (CRC). We sought to determine the association of pre-diagnosis body mass index (BMI) trajectories on mortality after CRC diagnosis. Methods: Utilizing the Multiethnic Cohort, we included adults aged 18–75 between 1 January 1993 and 1 January 2019 with a diagnosis of CRC and at least three available BMIs. The primary exposure, BMI, was subjected to group-based trajectory modeling (GBTM). We evaluated all-cause and CRC-specific mortality, using Cox proportional hazard (PH) models. Results: Of 924 persons, the median age was 60 years, and 54% were female. There was no statistically significant association between pre-cancer BMI trajectory and either all-cause or cancer-specific mortality. In competing risk analysis, the risk of CRC-specific mortality was higher for African Americans (HR = 1.56, 95% CI [1.00–2.43], p = 0.048) and smokers (HR = 1.59, 95% CI [1.10–2.32], p = 0.015). Risk of all-cause mortality was higher for Hawaiian persons (HR = 2.85, 95% CI [1.31–6.21], p = 0.009) and persons with diabetes (HR = 1.83, 95% CI [1.08–3.10], p = 0.026). Conclusions: Pre-diagnosis BMI trajectories were not associated with mortality after CRC diagnosis, whereas race/ethnicity, diabetes, and smoking were associated with an increased risk of death. Our findings suggest the obesity paradox alone does not account for mortality after CRC diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: This study examined the outcomes of patients with gallbladder cancer over 20 years in Saskatchewan, Canada, focusing on geographic, demographic, and clinical factors. A total of 331 patients diagnosed between 2000 and 2019 were included. The majority (64%) had advanced stage 4 disease, with a significant proportion (66%) being rural residents. Key factors associated with poorer overall survival included stage 4 disease, lack of surgery, older age, a higher neutrophil-to-lymphocyte ratio, and no referral to a regional cancer center. Among early-stage patients, stage III disease and urban residence were associated with worse disease-free survival. The findings highlight the late-stage diagnosis and referral challenges impacting the outcomes of gallbladder cancer. Background: Gallbladder cancer (GBC) is an uncommon cancer. This study aimed to determine the outcomes of GBC in relation to geographic, demographic, and clinical factors in a Canadian province from 2000 to 2019. Methods: This population-based retrospective cohort study included all patients diagnosed with gallbladder cancer (GBC) in Saskatchewan, Canada, from 2000 to 2019. Cox proportional multivariate regression analysis was conducted to identify factors associated with poorer outcomes. Results: In total, 331 patients with a median age of 74 years and male–female ratio of 1:2 were identified. Of these patients, 305 (92%) had a pathological diagnosis of GBC. Among patients with documented staging data, 64% had stage IV disease. A total of 217 (66%) patients were rural residents, and 149 (45%) were referred to a cancer center. The multivariate analysis for patients with stage I–III GBC showed that stage III disease [hazard ratio (HR), 2.63; 95% confidence interval (CI), 1.09–6.34)] and urban residence (HR, 2.20; 95% CI, 1.1–4.39) were correlated with inferior disease-free survival. For all patients, stage IV disease (HR, 3.02; 95% CI, 1.85–4.94), no referral to a cancer center (HR, 2.64; 95% CI, 1.51–4.62), lack of surgery (HR, 1.63; 95% CI, 1.03–2.57), a neutrophil–lymphocyte ratio of >3.2 (HR, 1.57; 1.05–2.36), and age of ≥70 years (HR, 1.51; 95% CI, 1.04–2.19) were correlated with inferior overall survival. Conclusions: In this real-world context, the majority of patients with GBC were diagnosed at a late stage and were not referred to a cancer center. For those with early-stage GBC, living in an urban area and having stage III disease were linked to worse outcomes. Across all stages of GBC, stage IV disease, older age, absence of surgery, lack of referral to a cancer center, and a high neutrophil-to-lymphocyte ratio were associated with poorer survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment personalization is essential in the era of precision medicine. Biomarkers are necessary to predict clinical outcomes and guide treatment selection to improve efficacy and reduce toxicity. Genomic human leukocyte antigen-class I (HLA-I) has been shown to correlate with outcomes among non-small cell lung cancer (NSCLC) patients treated with immunotherapy. Here, we investigate whether the HLA genotype is predictive of outcomes in regard to the combination of immunotherapy with chemotherapy. We found that the HLA-I supertypes HLA-A01 and -A03, but not HLA homozygosity, overall correlated with survival in NSCLC patients treated with immunochemotherapy. While further validation is needed, these results highlight the potential and variability of the HLA genotyping as a biomarker for immunotherapy delivery. Introduction: Maximal heterozygosity on the human leukocyte antigen (HLA) loci has been found to be associated with improved survival and development of immune-related adverse events (irAEs) among NSCLC patients treated with immunotherapy. Here, we investigated the effect of germline HLA-I/-II on clinical outcomes among NSCLC patients treated with first-line pembrolizumab in combination with chemotherapy. Method: We prospectively recruited patients with NSCLC who were commencing first-line pembrolizumab in combination with chemotherapy. DNA from white blood cells was used for high-resolution HLA-I/II typing. Results: Of the 65 patients recruited, 53 complied with the inclusion criteria. We did not find an association between HLA-I/-II homozygosity and clinical outcome among the studied population. However, the presence of HLA-A01 was associated with unfavourable PFS (HR = 2.32, 95%CI 1.13–4.77, p = 0.022) and worsening OS (HR = 2.86, 95%CI 1.06–7.70, p = 0.038). The presence of HLA-B27 was associated with improved PFS (HR = 0.35, 95%CI 0.18–0.71, p = 0.004) and trends toward improving OS. None of the HLA-I supertypes were associated with the development or worsening of irAEs. Conclusions: The absence of association between genomic HLA-I/-II homozygosity and clinical outcome among patients with advanced NSCLC treated with pembrolizumab in combination with chemotherapy might reflect a diminished role for HLA molecules among patients with low or no PD-L1. HLA-A01 and HLA-B27 might have a role in predicting clinical outcomes among this cohort of patients. Further studies are needed to explore biomarkers for this group of patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This study introduces a deep learning model designed to predict the 5-year recurrence risk of lung adenocarcinoma based on histopathology images. Using a dataset of 189 patients with 455 histopathology slides, our model demonstrated superior performance in risk stratification, achieving a hazard ratio of 2.29 (95% CI: 1.69–3.09, p < 0.005). This outperforms several existing deep learning methods, showcasing the potential of deep learning in automatically predicting lung adenocarcinoma recurrence risk. The superior performance of this model underscores the potential for deep learning models to be integrated into clinical workflows for more accurate and automated risk assessment in lung adenocarcinoma. This could lead to more personalized treatment strategies and better patient outcomes. Lung cancer is the leading cause of cancer-related death in the United States. Lung adenocarcinoma (LUAD) is one of the most common subtypes of lung cancer that can be treated with resection. While resection can be curative, there is a significant risk of recurrence, which necessitates close monitoring and additional treatment planning. Traditionally, microscopic evaluation of tumor grading in resected specimens is a standard pathologic practice that informs subsequent therapy and patient management. However, this approach is labor-intensive and subject to inter-observer variability. To address the challenge of accurately predicting recurrence, we propose a deep learning-based model to predict the 5-year recurrence of LUAD in patients following surgical resection. In our model, we introduce an innovative dual-attention architecture that significantly enhances computational efficiency. Our model demonstrates excellent performance in recurrent risk stratification, achieving a hazard ratio of 2.29 (95% CI: 1.69–3.09, p < 0.005), which outperforms several existing deep learning methods. This study contributes to ongoing efforts to use deep learning models for automatically learning histologic patterns from whole slide images (WSIs) and predicting LUAD recurrence risk, thereby improving the accuracy and efficiency of treatment decision making. [ABSTRACT FROM AUTHOR]

Simple Summary: This pilot study aims to identify the physical, mental, social, psychological, and health needs encountered by cancer survivors in order to propose and facilitate appropriate and tailored responses. To the best of our knowledge, this is one of the first multidimensional studies investigating this topic in Italy. Data show that the quality of life of cancer survivors is affected by cancer and its treatment, reporting more frailties than the general population, especially those over 65 years old. These findings could help develop multidisciplinary planning of survivorship care for the transition of patients from oncological management to primary healthcare. Background: Understanding the specific needs of cancer survivors is essential for healthcare policy. In Italy, dedicated studies are lacking, so we aimed to investigate the physical, mental, social, and health difficulties encountered by these patients. Methods: We conducted a cross-sectional study on breast or colorectal cancer survivors (people 5+ years free from it and its treatments) using an ad hoc survey including validated questionnaires (Grauer–Palombi, SF-36, PREDIMED). Participants were recruited within the Oncology Unit of the "Policlinico Tor Vergata", Italy. Results: A total of 62 patients (80.6% females; years range: 37–87) agreed to be interviewed. A profile of cancer survivors was drafted: an overaged person with multiple co-morbidities, not well-nourished, adhering to the Mediterranean diet, reporting critical conditions as for physical and functional status. The mean number of co-morbidities was 3.6 ± 2.4 SD, with a statistically significant difference between age groups (under and over 65). Compared to the general population, the sample showed more frailties, especially when >65. The risk of having multimorbidity (four or more co-morbidities) significantly increased in those over 65 (OR: 4.72; CI: 1.43–15.59). Conclusion: There is an urgent need for survivorship care planning for the patient-centered continuum of care. Assessing and monitoring their specific needs will help propose appropriate and tailored responses. [ABSTRACT FROM AUTHOR]

Simple Summary: The study analyzed income disparities in 5-year survival rates (5YSR) among cancer patients in South Korea from 2002 to 2018. Overall, 5YSR improved from 2002–2006 to 2014–2018, particularly for lung, liver, and stomach cancers. The Slope Index of Inequality (SII) indicated significant income-related disparities, with higher survival rates associated with higher incomes, notably for lung and liver cancers. The SII for lung, liver, and stomach cancer increased, while that of thyroid, breast, cervical, prostate, and colorectal cancer decreased over the study period. The findings highlight persistent income-related gaps in cancer survival despite overall improvements, emphasizing the need for targeted interventions to address socioeconomic inequalities in cancer care outcomes. Background: The overall survival rates among cancer patients have been improving. However, the increase in survival is not uniform across socioeconomic status. Thus, we investigated income disparities in the 5-year survival rate (5YSR) in cancer patients and the temporal trends. Methods: This study used a national cancer cohort from 2002 to 2018 that was established by linking the Korea Central Cancer Registry and the National Health Insurance Service (NHIS) claim database to calculate the cancer survival rate by income level in the Republic of Korea. Survival data were available from 2002 onward, and the analysis was based on the actuarial method. We compared the survival of the earliest available 5-year period of 2002–2006 and the latest available 5-year period of 2014–2018, observing until 31 December 2021. Income level was classified into six categories: Medical Aid beneficiaries and five NHIS subtypes according to insurance premium. The slope index of inequality (SII) and relative index of inequality were used to measure absolute and relative differences in 5YSR by income, respectively. Results: The 5YSR between the 2002–2006 and 2014–2018 periods for all cancers improved. A significant improvement in 5-year survival rates (5YSR) over the study period was observed in lung, liver, and stomach cancer. The SII of survival rates for lung (17.5, 95% confidence interval (CI) 7.0–28.1), liver (15.1, 95% CI 10.9–19.2), stomach (13.9, 95% CI 3.2–24.7), colorectal (11.4, 95% CI 0.9–22.0), and prostate (10.7, 95% CI 2.5–18.8) cancer was significantly higher, implying higher survival rates as income levels increased. The SII for lung, liver, and stomach cancer increased, while that of thyroid, breast, cervical, prostate, and colorectal cancer decreased over the study period. Conclusions: Although substantial improvement in the 5YSR was observed across cancer types and income levels from 2002 to 2018, this increase was not uniformly distributed across income levels. Our study revealed persistent income disparities in the survival of cancer patients, particularly for lung and liver cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Socioeconomic inequalities in cancer incidence and mortality have been studied extensively, but there has been no investigation of the spatial distribution of incidence and mortality within a country to see if they are consistent with each other and with deprivation. To fill this gap, we examined the spatial distribution of cancer incidence and mortality and their association with each other and with socioeconomic deprivation at the municipal level in Hungary, one of the countries with the most unfavourable cancer burden in the world. For different types of cancer, while mortality always showed positive associations with deprivation, there was only partial overlap between areas of high incidence and mortality across the country, with clusters often independent of deprivation. Even where incidence and mortality overlapped geographically, there were often significant differences in mortality risk. Discrepancies in the spatial distribution of cancer incidence and mortality are indicators of an unmet need for cancer prevention and/or treatment. There is a rich body of literature on the distribution of cancer incidence and mortality in socioeconomically different world regions, but none of the studies has compared the spatial distribution of mortality and incidence to see if they are consistent with each other. All malignant neoplasms combined and cervical, colorectal, breast, pancreatic, lung, and oral cancers separately were studied in the Hungarian population aged 25–64 years for 2007–2018 at the municipality level by sex. In each case, the spatial distribution of incidence and mortality were compared with each other and with the level of deprivation using disease mapping, spatial regression, risk analysis, and spatial scan statistics. A positive association between deprivation and mortality was found for each type of cancer, but there was no significant association for male colorectal cancer (relative risk (RR) 1.00; 95% credible interval (CI) 0.99–1.02), pancreatic cancer (RR: 1.01; 95%CI 0.98–1.04), and female colorectal cancer incidence (RR: 1.01; 95%CI 0.99–1.03), whereas a negative association for breast cancer (RR: 0.98; 95%CI 0.96–0.99) was found. Disease mapping analyses showed only partial overlap between areas of high incidence and mortality, often independent of deprivation. Our results highlight not only the diverse relationship between cancer burden and deprivation, but also the inconsistent relationship between cancer incidence and mortality, pointing to areas with populations that require special public health attention. [ABSTRACT FROM AUTHOR]

Simple Summary: The combination of chemoradiotherapy followed by surgery (trimodality therapy) is considered standard of care for patients with locally advanced esophageal adenocarcinoma, but many potential candidates for surgery receive curative-intent chemoradiotherapy alone. This study compared the outcomes of patients who received trimodality therapy to those who received curative-intent chemoradiotherapy. Our primary analysis found that trimodality therapy reduced the risk of local tumor recurrences, but we did not detect statistically significant differences in the risks of distant metastases or mortality. These results can help patients and clinicians make informed treatment decisions, although further studies are needed to refine our understanding of the trade-offs between the two treatment strategies. The optimal management of patients with locally advanced esophageal adenocarcinoma is unclear. Neoadjuvant chemoradiotherapy followed by esophagectomy (trimodality therapy) is supported as a standard of care, but definitive chemoradiotherapy is frequently given in practice to patients who may have been surgical candidates. This multi-institutional retrospective cohort study compared the outcomes of consecutive patients diagnosed with stage II to IVA esophageal adenocarcinoma between 2004 and 2018 who planned to undergo trimodality therapy or definitive chemoradiotherapy. A total of 493 patients were included, of whom 435 intended to undergo trimodality therapy and 56 intended to undergo definitive chemoradiotherapy. After a median follow-up of 7.3 years, trimodality therapy was associated with a lower risk of locoregional failure (5-year risk, 30.5% vs. 61.3%; HR, 0.39; 95% CI, 0.24–0.62; p < 0.001 ) but not distant metastases (5-year risk, 58.2% vs. 53.9%; HR, 1.21; 95% CI, 0.77–1.91; p = 0.40 ). There were no differences in overall survival (HR, 0.78; 95% CI, 0.56–1.09; p = 0.14 ) or cancer-specific survival (HR, 0.83; 95% CI, 0.57–1.21; p = 0.33 ). Findings were consistent on propensity score-matched sensitivity analyses. In conclusion, trimodality therapy was associated with a lower risk of locoregional failure, but this did not translate into a significantly lower risk of distant failure or improved survival. Further studies are required to accurately estimate the trade-offs between the two treatment strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer and type 2 diabetes mellitus are highly prevalent and closely related diseases. Type 2 diabetes increases the risk of breast cancer. Our retrospective matched cohort study involving 318 women with type 2 diabetes assessed the evolution of cardiometabolic parameters and diabetic complications in women with (n = 106) and without subsequent breast cancer (n = 212). Over a 7-year follow-up period, women with breast cancer had worse glycemic control but not higher rates of diabetic complications compared to women without breast cancer. During breast cancer (BC), cardiometabolic disorders can worsen prognosis, particularly in women with type 2 diabetes mellitus (T2DM). This study aimed to determine the impact of BC diagnosis on cardiometabolic parameters and the incidence of complication in women over 50 years of age (90% aged ≥ 65 years) with pre-existing T2DM. Using primary care registries from Asturias (Spain), a total of 106 women diagnosed with T2DM followed by BC were selected and matched with women with T2DM (n = 212) in a cohort study. Indicators of cardiometabolic health and microvascular complications associated with T2DM were collected. Women were monitored from two years prior to five years after BC diagnosis. Conditional logistic regressions were used to compare the adjusted odds of staying below each indicator's threshold. During follow-up, women with T2DM+BC had a higher risk of fasting blood glucose ≥126 mg/dL (adjusted odds ratio [aOR] = 1.83; 95% confidence interval [CI95%]: 1.01–3.32) and glycosylated hemoglobin (Hb1Ac) ≥ 48 mmol/mol or 6.5% (aOR: 2.44; IC95%: 1.21–4.91). There was no difference between the groups regarding the incidence of microvascular complications. BC incidence negatively impacted the glycemic control of Spanish women with pre-existing T2DM measured by basal blood glucose and HbA1c, but not cardiometabolic health indicators or T2DM complications. [ABSTRACT FROM AUTHOR]

Simple Summary: Pain is a common symptom that affects individuals with cancer. This study, using data from the National Health Interview Survey, explored how household income relates to chronic pain among cancer survivors. It found that lower-income survivors, those below 200% of the federal poverty level (FPL), were more likely to report chronic pain lasting at least 3 months and pain that significantly limited their daily activities. Compared to higher-income survivors (at least 400% FPL), those with lower incomes had higher odds of experiencing chronic pain and its impact on daily life. Additionally, opioid use for pain management was more common among lower-income survivors, while higher-income survivors tended to use alternative methods like yoga, chiropractic care, and physical therapy. This study emphasizes the need for targeted efforts to address healthcare disparities and improve pain management for all cancer survivors, regardless of their income level. Pain is a prevalent issue among cancer patients, yet its link with socioeconomic status has not been thoroughly examined. This study investigated chronic pain (lasting ≥3 months) and high-impact pain (chronic pain limiting activities) among cancer survivors based on household income relative to the federal poverty level (FPL), using data from the National Health Interview Survey (2019–2020). Of the 4585 participants with a history of solid cancers, 1649 (36.3%) reported chronic pain and 554 (12.6%) reported high-impact chronic pain. After adjustment, participants with incomes < 200% FPL had significantly higher odds of chronic pain (adjusted odds ratio [aOR]: 1.60, 95% CI: 1.25–2.05) and high-impact chronic pain (aOR: 1.73, 95% CI: 1.09–2.74) compared to those with incomes ≥ 400% FPL. Opioid use for chronic pain was most prevalent among those with incomes < 200% FPL (28.3%) compared to those with 200–399% (21.3%) and ≥400% (19.0%). Higher-income participants reported greater use of alternative pain management methods such as yoga (50.5%), chiropractic care (44.8%), and physical therapy (44.3%). This study highlights the association between household income and chronic pain outcomes among cancer survivors, emphasizing the necessity for targeted interventions to mitigate healthcare access disparities and improve pain management for all individuals affected by cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: This research investigates how a condition called hydronephrosis—where the kidney swells due to blocked urine flow as a result of advanced bladder cancer—affects the outcomes of a surgical procedure called robot-assisted radical cystectomy, used to remove the bladder in this group of patients. The study analysed data from multiple Asian expert centers to see if patients with hydronephrosis before surgery had different outcomes compared to those without it. Results showed that patients with hydronephrosis tended to have worse survival rates and more complications following surgery. Understanding these impacts helps doctors better predict and improve treatment outcomes for bladder cancer patients. This study's findings can lead to more personalised and effective treatment plans, enhancing patient care. Introduction: Robot-assisted radical cystectomy (RARC) has gained momentum in the management of muscle invasive bladder cancer (MIBC). Predictors of RARC outcomes are not thoroughly studied. We aim to investigate the implications of preoperative hydronephrosis on oncological outcomes. Patients and Methods: This study analysed data from the Asian RARC consortium, a multicentre registry involving nine Asian centres. Cases were divided into two groups according to the presence or absence of pre-operative hydronephrosis. Background characteristics, operative details, perioperative outcomes, and oncological results were reviewed. Outcomes were (1) survival outcomes, including 10-year disease-free survival (DFS) and overall survival (OS), and (2) perioperative and pathological results. Multivariate regression analyses were performed on survival outcomes. Results: From 2007 to 2020, 536 non-metastatic MIBC patients receiving RARC were analysed. 429 had no hydronephrosis (80.0%), and 107 (20.0%) had hydronephrosis. Hydronephrosis was found to be predictive of inferior DFS (HR = 1.701, p = 0.003, 95% CI = 1.196–2.418) and OS (HR = 1.834, p = 0.008, 95% CI = 1.173–2.866). Subgroup analysis demonstrated differences in the T2-or-above subgroup (HR = 1.65; p = 0.004 in DFS and HR = 1.888; p = 0.008 in OS) and the T3-or-above subgroup (HR = 1.757; p = 0.017 in DFS and HR = 1.807; p = 0.034 in OS). Conclusions: The presence of preoperative hydronephrosis among MIBC patients carries additional prognostic implications on top of tumour staging. Its importance in case selection needs to be highlighted. [ABSTRACT FROM AUTHOR]

Simple Summary: This study analyzed over eighty thousand adverse event reports from the Food and Drug Administration's Adverse Event Reporting System to identify records of patients administered with immune checkpoint inhibitors as monotherapy for various malignancies. We analyzed whether co-occurring viral, bacterial, or fungal infections increased the risk of developing immune-related adverse events, such as pneumonitis, sarcoidosis, myocarditis, nephritis, colitis, hepatitis, and others, in cancer patients treated with those inhibitors and quantified the association. We have found a statistically significant, at the 95% confidence level, association between co-occurring infections and immune-related adverse events in cancer patients treated with immune checkpoint inhibitors. Therapeutic antibodies designed to target three immune checkpoint proteins have been applied in the treatment of various malignancies, including small and non-small cell lung cancers, melanoma, renal cell carcinoma, and others. These treatments combat cancers by reactivating cytotoxic T cells. Nevertheless, this mode of action was found to be associated with a broad range of immune-related adverse events (irAEs), including pneumonitis, sarcoidosis, myocarditis, nephritis, colitis, and hepatitis. Depending on their severity, these irAEs often necessitate the suspension or discontinuation of treatment and, in rare instances, may lead to fatalities. We analyzed over nineteen million reports and identified over eighty thousand adverse event reports from patients treated with immune checkpoint inhibitors submitted to the Food and Drug Administration's Adverse Event Reporting System MedWatch. Reports concerning pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab, atezolizumab, and ipilimumab revealed a statistically significant association between the irAEs and concurrent infectious diseases for five out of seven treatments. Furthermore, the association trend was preserved across all three types of checkpoint inhibitors and each of the five individual therapeutic agent cohorts, while the remaining two showed the same trend, but an increased confidence interval, due to an insufficient number of records. [ABSTRACT FROM AUTHOR]

Simple Summary: Although atezolizumab plus bevacizumab is the standard first-line treatment for patients with advanced HCC, the optimal second-line regimen remains unknown. In this meta-analysis, we examined the subsequent regimen after the failure of atezolizumab–bevacizumab and found that sequential multitargeted tyrosine kinase inhibitors, including sorafenib and lenvatinib, significantly prolonged the survival of patients, with a pooled OS of 11.45 months and a PFS of 3.78 months, respectively. Moreover, the subsequent use of sorafenib or lenvatinib has manageable toxicity. Therefore, our data indicate that sorafenib or lenvatinib treatment is a rational option for patients with advanced HCC after progression on atezolizumab–bevacizumab. Background: Although atezolizumab plus bevacizumab (hereinafter, atezolizumab–bevacizumab) is the standard first-line treatment for patients with advanced HCC, the optimal second-line regimen remains unknown. This study evaluated the efficacy and safety of sorafenib and lenvatinib in patients with advanced HCC that progressed under atezolizumab–bevacizumab treatment. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed, Embase, and the Cochrane Library for articles published before November 2023. Random-effects meta-analysis was performed to determine the pooled objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS), comparing patients who received sorafenib versus lenvatinib. Results: Seven studies involving 387 patients were included. The pooled ORR, DCR, OS, and PFS for sorafenib and lenvatinib together were 26% (95% CI: 14–43%), 63% (95% CI: 47–77%), 11.45 months (95% CI: 7.12–15.77, I2 = 92%, p < 0.01), and 3.78 months (95% CI: 2.34–5.23, I2 = 67%, p = 0.02), respectively. Although lenvatinib users had a longer median OS (12.42 vs. 10.75 months) and PFS (5.15 vs. 2.58 months) than sorafenib users, the pooled ORR, DCR, median OS, and PFS for these medications were comparable. Additionally, the distributions of all-grade and grade ≥ 3 adverse events for sorafenib and lenvatinib were comparable to those for these two medications when used as first-line therapies. Conclusions: Sorafenib or lenvatinib can provide effective treatment with manageable toxicity in patients with advanced HCC after disease progression under atezolizumab–bevacizumab. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is the second most common cancer among males and is a significant cause of morbidity and mortality. The chemokine C-C motif ligand 2 (CCL2) and its receptor C-C motif chemokine receptor 2 (CCR2) are expressed in prostate cancer but their prognostic value is unclear. This study investigated CCL2 and CCR2 as prognostic biomarkers in locally advanced prostate cancer using the large TROG 03.04 RADAR clinical trial cohort. The results demonstrate that despite being expressed in prostate tumours, CCR2 and CCL2 have no prognostic value in the disease. This study investigated the prognostic value of the chemokine C-C motif ligand 2 (CCL2) and its receptor C-C motif chemokine receptor 2 (CCR2) expression in locally advanced prostate cancer treated with radiotherapy and androgen deprivation using the 10-year outcome data from the TROG 03.04 RADAR clinical trial. CCL2 and CCR2 protein expression in prostate cancer biopsies at the time of diagnosis were quantified by immunohistochemistry and digital quantification. CCR2 protein expression was detected in prostate cancer cells and was associated with prostate-specific antigen serum concentration (p = 0.045). However, neither CCL2 nor CCR2 tissue expression could predict prostate cancer progression, or other clinicopathological parameters including perineural invasion and patient outcome. In serum samples, CCL2 concentration at the time of diagnosis, as assayed by enzyme-linked immunosorbent assay, was significantly higher in patients with prostate cancer compared with benign prostatic hyperplasia (median difference 0.22 ng/mL, 95% CI, 0.17–0.30) (p < 0.0001) and normal controls (median difference 0.13 ng/mL, 95% CI, 0.13–0.17) (p < 0.0001). However, circulating CCL2 was not statistically significant as a predictor of disease progression and patient outcome. In conclusion, this study shows that although CCL2 and CCR2 are expressed in prostate cancer, with an increased level of CCL2 in the serum, neither CCL2 nor CCR2 expression has a clinical prognostic value in locally advanced prostate cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the continuous therapeutic efforts metastatic renal cell carcinoma (mRCC) is a dreadful disease, but the many options available provide an horizon of hope for these patients. Sequential therapy based on vascular endothelial growth factor-tyrosine kinase inhibitors (VEGFR-TKI) continues in use. We present a nomogram for a more individualized and accurate estimation of cancer-specific survival (CSS) for patients with clear-cell (CC) mRCC treated with nephrectomy and VEGFR-TK, based on four independent clinical predictors: Eastern Cooperative Oncology Group (ECOG) status; International Metastatic RCC Database Consortium (IMDC) score; Morphology, Attenuation, Size and Structure (MASS) and Response Evaluation Criteria in Solid Tumors (RECIST) response criteria. This tool may be useful to clinicians assessing risk and prognosis of patients with mRCC. (1) Objective: To develop a clinically useful nomogram that may provide a more individualized and accurate estimation of cancer-specific survival (CSS) for patients with clear-cell (CC) metastatic renal cell carcinoma (mRCC) treated with nephrectomy and vascular endothelial growth factor receptor–tyrosine kinase inhibitor (VEGFR-TKI)-based sequential therapy. (2) Methods: A prospectively maintained database of 145 patients with mRCC treated between 2008 and 2018 was analyzed to predict the CSS of patients receiving sunitinib and second- and third-line therapies according to current standards of practice. A nomogram based on four independent clinical predictors (Eastern Cooperative Oncology Group status, International Metastatic RCC Database Consortium score, the Morphology, Attenuation, Size and Structure criteria and Response Evaluation Criteria in Solid Tumors response criteria) was calculated. The corresponding 1- to 10-year CSS probabilities were then determined from the nomogram. (3) Results: The median age was 60 years (95% CI 57.9–61.4). The disease was metastatic at diagnosis in 59 (40.7%), and 86 (59.3%) developed metastasis during follow-up. Patients were followed for a median 48 (IQR 72; 95% CI 56–75.7) months after first-line VEGFR-TKI initiation. The concordance probability estimator value for the nomogram is 0.778 ± 0.02 (mean ± SE). (4) Conclusions: A nomogram to predict CSS in patients with CC mRCC that incorporates patient status, clinical risk classification and response criteria to first-line VEGFR-TKI at 3 months is presented. This new tool may be useful to clinicians assessing the risk and prognosis of patients with mRCC. [ABSTRACT FROM AUTHOR]

Simple Summary: Angiogenesis is a synchronous mechanism of new blood vessel formation that is controlled by pro- and anti-angiogenic factors. Angiogenesis differs from tissue to tissue, especially in pathological conditions. The exact nature of the co-operation between angiogenic markers is still unknown. Herein, we describe the possible critical changes in VEGF-A, TGF-β1, ANG1, ANG2, and HIF-1α in ectopic endometriosis (with elevated pro-angiogenic factors in all studied fields), in ovarian endometrioid adenocarcinoma (showing typical upregulation on the TGF-β1 axis), and two different types of endometrial carcinoma (with an extreme pathological ANG2/ANG1 axis for mixed mesodermal tumors). Understanding the angiogenic mechanism within pathological tissues could help to improve angiogenic treatment strategies and lead to better prognoses. A characteristic feature of uterine pathologies is a specific change in cell metabolism, which predominantly manifests as a shift in the need for nutrients, thereby directing cells to engage in different angiogenic marker activities. Angiogenesis is one of the main signals supporting the survival and development of cells and tissues not only under physiological conditions. Therefore, it is necessary that we understand pathological hyperactivation in all uterine diseases, from endometriosis through ovarian endometrioid adenocarcinoma to malignant transformed cells of the uterine epithelium and body. This work presents the gene expression results of selected angiogenesis targets (VEGF-A, TGF-β1, ANG1/2, and HIF-1α), cell migration, and cell–cell interaction determined in vitro. Our results suggest that angiogenesis varies in the tested pathological conditions (ectopic endometriosis—12Z; ovarian endometrioid adenocarcinoma—A2780; tumors—SK-UT-1 and RL-95-2) compared to physiological angiogenesis (HME1). The differential expression of angiogenic factors may contribute (or is a contributing factor) to the observed differences to acknowledge an inherent variability in angiogenesis among cell lines. Determining the genomic phenomena responsible for processes associated with inadequate angiogenesis in the pelvic region could help us to develop individual treatment strategies and explain resistance to treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: A model predicting responders to corticosteroid switch during abiraterone therapy in patients with metastatic castration-resistant prostate cancer is warranted. The model using logistic regression was developed in a cohort of 67 and validated in another cohort of 42 patients. The use of this model is easy and all needed parameters are available from routine laboratory and history of patients. The overall accuracy was 92%. Multivariate analysis revealed that responsiveness was a marker of longer treatment duration and overall survival. For non-responders a new systemic treatment was indicated. Background: The aim was to elaborate a predictive model to find responders for the corticosteroid switch (from prednisolone to dexamethasone) at the first prostate-specific antigen (PSA) progression (≥25% increase) during abiraterone acetate (AA) treatment of metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: If PSA has decreased (≥25%) after switch, patients were considered responders. Logistic regression of 19 dichotomized parameters from routine laboratory and patients' history was used to find the best model in a cohort of 67 patients. The model was validated in another cohort of 42 patients. Results: The model provided 92.5% and 90.5% accuracy in the testing and the validation cohorts, respectively. Overall the accuracy was 91.7%. The AUC of ROC curve was 0.92 (95% CI 0.85–0.96). After a median follow-up of 27.9 (26.3–84) months, the median AA+dexamethasone treatment duration (TD) in non-responders and responders was 4.7 (3.1–6.5) and 11.1 (8.5–12.9) months and the median overall survival (OS) was 23.2 (15.6–25.8) and 33.5 (26.1–38) months, respectively. Multivariate Cox regression revealed that responsiveness was an independent marker of TD and OS. Conclusions: A high accuracy model was developed for mCRPC patients in predicting cases which might benefit from the switch. For non-responders, induction of the next systemic treatment is indicated. [ABSTRACT FROM AUTHOR]

Simple Summary: The mortality of hepatocellular carcinoma (HCC) is rising globally, against the trend of other cancers. People with liver cirrhosis, even after hepatitis C treatment still face a high risk of HCC, requiring ongoing enrolment in HCC surveillance, and new technologies to improve diagnostic sensitivity are being explored. However, their impact on HCC survival remains uncertain relative to improving adherence to existing surveillance methods. This study uses mathematical modeling to assess how different strategies can reduce deaths from liver cancer in people with cirrhosis after being cured of hepatitis C. We compared the impact of improved adherence to ultrasound screening with increased HCC imaging sensitivity on HCC survival. Notably, we found that even modest enhancements in surveillance adherence (5–10 percentage point increases) exhibited significant survival benefits for people with hepatitis C-related cirrhosis, outperforming improvements in diagnostic sensitivity. Background & Aims: Hepatocellular carcinoma (HCC) presents a significant global health challenge, particularly among individuals with liver cirrhosis, with hepatitis C (HCV) a major cause. In people with HCV-related cirrhosis, an increased risk of HCC remains after cure. HCC surveillance with six monthly ultrasounds has been shown to improve survival. However, adherence to biannual screening is currently suboptimal. This study aimed to evaluate the effect of increased HCC surveillance uptake and improved ultrasound sensitivity on mortality among people with HCV-related cirrhosis post HCV cure. Methods: This study utilized mathematical modelling to assess HCC progression, surveillance, diagnosis, and treatment among individuals with cirrhosis who had successfully been treated for HCV. The deterministic compartmental model incorporated Barcelona Clinic Liver Cancer (BCLC) stages to simulate disease progression and diagnosis probabilities in 100 people with cirrhosis who had successfully been treated for hepatitis C over 10 years. Four interventions were modelled to assess their potential for improving life expectancy: realistic improvements to surveillance adherence, optimistic improvements to surveillance adherence, diagnosis sensitivity enhancements, and improved treatment efficacy Results: Realistic adherence improvements resulted in 9.8 (95% CI 7.9, 11.6) life years gained per cohort of 100 over a 10-year intervention period; 17.2 (13.9, 20.3) life years were achieved in optimistic adherence improvements. Diagnosis sensitivity improvements led to a 7.0 (3.6, 13.8) year gain in life years, and treatment improvements improved life years by 9.0 (7.5, 10.3) years. Conclusions: Regular HCC ultrasound surveillance remains crucial to reduce mortality among people with cured hepatitis C and cirrhosis. Our study highlights that even minor enhancements to adherence to ultrasound surveillance can significantly boost life expectancy across populations more effectively than strategies that increase surveillance sensitivity or treatment efficacy. [ABSTRACT FROM AUTHOR]

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

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

Simple Summary: This research investigates whether a diagnostic technique called ureteroscopy (URS), performed before surgery for removing the kidney and ureter, influences the likelihood of cancer recurrence in the bladder in patients with upper tract urothelial carcinoma (UTUC). Data from a multicentre international registry were analysed to compare patients who underwent URS before their surgery with those who did not. The study found that patients who had URS prior to surgery experienced a higher rate of cancer recurrence in the bladder. These results highlight the need for careful consideration of the use of URS in the diagnostic process for UTUC, as it could affect long-term outcomes. This information is crucial for clinicians in optimizing treatment strategies and improving patient care. (1) Introduction: Diagnostic ureteroscopy (URS) is an important component in the workup of upper tract urothelial carcinoma (UTUC). Whether URS was associated with increased recurrence in the bladder was not fully concluded. The current study aimed to evaluate the implication of URS on the incidences of intravesical recurrence following radical nephroureterectomy (RNU) in non-metastatic UTUC patients without prior history of bladder cancer via multi-institutional data. (2) Patients and Methods: Data were obtained from the Clinical Research Office of the Endourology Society Urothelial Carcinomas of the Upper Tract (CROES-UTUC) registry, a prospective, multicentre database. Patients with non-metastatic UTUC treated with RNU were divided into two groups: those undergoing upfront RNU and those having diagnostic URS prior to RNU. Intravesical recurrence-free survival (IVRS) was the primary endpoint, evaluated through Kaplan–Meier analysis and multivariate Cox regression. Cases with adequate follow-up data were included. (3) Results: The analysis included 269 patients. Of these, 137 (50.9%) received upfront RNU and 132 (49.1%) received pre-RNU URS. The URS group exhibited an inferior 24-month IVRS compared to the upfront RNU group (HR = 1.705, 95% CI = 1.082–2.688; p = 0.020). Multivariate analysis confirmed URS as the only significant predictor of IVR (p = 0.019). Ureteric access sheath usage, flexible ureteroscopy, ureteric biopsy, retrograde contrast studies, and the duration of URS did not significantly affect IVRS. (4) Conclusions: Diagnostic URS prior to RNU was found to be associated with an increased risk of IVR in patients with UTUC. The risk was not significantly influenced by auxiliary procedures during URS. Physicians were advised to meticulously evaluate the necessity of diagnostic URS. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence of metastatic melanoma is rising, making it imperative to identify patients who do not benefit from immunotherapy. This study aimed to develop a radiomic biomarker, using segmentations from 146 baseline and 146 first follow-up CT scans, to predict best overall response, progression-free survival, and overall survival across various immunotherapies. We volumetrically segmented the total tumour load, excluding cerebral metastases. This study also examined whether reducing the number of segmented metastases per patient affects predictive accuracy. The findings suggest that delta radiomics could enhance the prediction of best overall response, progression-free survival, and overall survival in metastatic melanoma patients undergoing first-line immunotherapy. Although volumetric whole tumour load segmentation is complex, it may provide predictive benefits. Background: The prevalence of metastatic melanoma is increasing, necessitating the identification of patients who do not benefit from immunotherapy. This study aimed to develop a radiomic biomarker based on the segmentation of all metastases at baseline and the first follow-up CT for the endpoints best overall response (BOR), progression-free survival (PFS), and overall survival (OS), encompassing various immunotherapies. Additionally, this study investigated whether reducing the number of segmented metastases per patient affects predictive capacity. Methods: The total tumour load, excluding cerebral metastases, from 146 baseline and 146 first follow-up CTs of melanoma patients treated with first-line immunotherapy was volumetrically segmented. Twenty-one random forest models were trained and compared for the endpoints BOR; PFS at 6, 9, and 12 months; and OS at 6, 9, and 12 months, using as input either only clinical parameters, whole-tumour-load delta radiomics plus clinical parameters, or delta radiomics from the largest ten metastases plus clinical parameters. Results: The whole-tumour-load delta radiomics model performed best for BOR (AUC 0.81); PFS at 6, 9, and 12 months (AUC 0.82, 0.80, and 0.77); and OS at 6 months (AUC 0.74). The model using delta radiomics from the largest ten metastases performed best for OS at 9 and 12 months (AUC 0.71 and 0.75). Although the radiomic models were numerically superior to the clinical model, statistical significance was not reached. Conclusions: The findings indicate that delta radiomics may offer additional value for predicting BOR, PFS, and OS in metastatic melanoma patients undergoing first-line immunotherapy. Despite its complexity, volumetric whole-tumour-load segmentation could be advantageous. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is the most common cancer detected among men and it is the second leading cause of death. According to the WHO, cobalt is probably involved in carcinogenesis. However, there are no studies related to cobalt levels and survival in prostate cancer patients. The aim of this prospective study was to investigate the relationship between serum cobalt levels and survival among prostate cancer patients taking into consideration prostate cancer-specific deaths and non-cancer causes of death. Our findings, based on 261 Polish prostate cancer patients, show that individuals with high serum cobalt levels have a significantly worse survival compared to participants with low serum cobalt levels. Prostate cancer is the most common cancer diagnosed in men and the second leading cause of death in male cancer patients. The WHO suggests that cobalt is involved in the carcinogenesis of prostate cancer. There are, however, no studies associating cobalt levels and prostate cancer patient survival. In this study, 261 Polish prostate cancer (n = 261) patients were recruited into a prospective cohort between 2009 and 2015. Serum cobalt levels were measured using ICP-MS after prostate cancer diagnosis and before treatment. All study participants were assigned into quartiles (QI-QIV) based on the distribution of serum cobalt levels among censored patients. Univariable and multivariable COX regression models were used to calculate hazard ratios (HRs) for each serum cobalt level quartile. We found a significant relationship between high serum cobalt levels and poor prostate cancer patient total survival (HR = 2.60; 95% CI: 1.17–5.82; p = 0.02). In relation to prostate cancer patients who died as a result of other non-cancer causes, the association with high levels of cobalt was even stronger (HR = 3.67; 95% CI: 1.03–13.00; p = 0.04). The impact of high serum cobalt levels on overall survival of prostate cancer-specific-related deaths was not statistically significant. [ABSTRACT FROM AUTHOR]

Simple Summary: Chemotoxicity in colorectal cancer (CRC) patients impacts treatment compliance, survival, and quality of life. While clinician-reported chemotoxicity predicts rehospitalization and survival, a comprehensive understanding is lacking. This systematic review and meta-analysis studied chemotoxicity in CRC patients. The study found that 45.7% of patients experienced overall moderate-to-severe toxicities, with gastrointestinal toxicity (22.9%) and neuropathy or neutropenia (17.9%) being the most common. Risk factors included malnutrition, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low quality of life. Age was linked to neutropenia and gastrointestinal toxicity. Older adults had higher overall and gastrointestinal toxicities but lower neutropenia than younger adults. The study underscores the need for close monitoring and management of chemotoxicity in CRC patients. Community contributions have been instrumental in raising awareness about these issues, advocating for patient support, and future research to improve treatment toxicities in CRC. Background: Colorectal cancer (CRC) patients experience multiple types of chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine chemotoxicity's prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: −1.44) and GI toxicity (β:1.85) (p-values < 0.01). Older adults (>65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (p-values < 0.05). Conclusions. Our findings highlight the importance of closely monitoring and managing chemotoxicity in CRC patients receiving chemotherapy. [ABSTRACT FROM AUTHOR]

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

Simple Summary: This study is a real-world study on a large cohort of patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who progressed on osimertinib, focusing on access to subsequent treatments and progression patterns, including central nervous system (CNS) progression. Almost half of these patients had no access to further treatments due to worsening of clinical conditions or death. The outcomes of standard platinum-based chemotherapy were dismal and in line with those reported in the literature. Notably, intracranial disease progression was a rare event during osimertinib, whereas it occurred in half the patients during standard chemotherapy. Overall, the data highlight the clinical unmet needs in the treatment sequencing of single agent osimertinib and platinum-based chemotherapy alone, confirming the role of combination approaches and treatments in improving CNS control. Background: Platinum-based chemotherapy is the current standard treatment option in patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who progress on osimertinib. However, outcomes with chemotherapy are dismal, and the treatment of central nervous system (CNS) disease is an unmet need in this setting. Methods: Patients with EGFR-mutant NSCLC who were candidates to receive osimertinib in the metastatic setting at our Center from 2015 to 2022 were retrospectively evaluated to identify patients who received standard platinum-based chemotherapy post-osimertinib. Data were collected on treatment outcomes, with a focus on brain metastases and progression patterns. Results: A total of 220 patients received indication for osimertinib in the study period; n = 176 had adequate follow-up data. Overall, n = 117 patients experienced disease progression on osimertinib. The median time to osimertinib progressive disease (PD) was 15 months (95% confidence interval CI 13–18). Of them, 51 patients (45%) had no access to further treatments. Of the remaining patients, n = 8 received experimental treatments, and n = 55 received standard platinum-based chemotherapy and were considered for this study. Median duration of chemotherapy was 3 months (95% CI 2–5); the best responses among 53 evaluable patients were observed as follows: 15% partial response/complete response (PR/CR), 40% stable disease (SD), 45% PD. Median progression-free survival (PFS) and overall survival (OS) were 3 (95% CI 2–5) and 10 (95% CI 6–15) months, respectively. All patients had baseline and follow-up brain radiologic assessments, and n = 23 had brain metastases at the start of chemotherapy. With a median follow-up of 13 months, intracranial PD occurred in 47% patients, being the first site of PD in 59% of cases. The median time for intracranial (IC) PD was 2 months (95% CI 2–7). IC PD occurred as oligometastatic in 29%, whereas in 71% of cases, it was associated with systemic PD. Conclusions: Access to subsequent treatments and CNS progression are confirmed unmet needs in EGFR-mutant NSCLC patients. Clinical and CNS-specific outcomes in patients receiving standard chemotherapy after the failure of osimertinib are dismal. Novel upfront treatment options with demonstrated prolonged PFS and better CNS outcomes may help address this important issue. [ABSTRACT FROM AUTHOR]

Simple Summary: Females prenatally exposed to diethylstilbestrol have an elevated risk of severe cervical dysplasia and some cancers, while testicular cancer is increased in males. We assessed these associations in the prenatally exposed female's offspring (third generation). Based on third-generation females' self-reports, diethylstilbestrol exposure was not associated with risks of overall cancer, breast cancer, or severe cervical dysplasia. Borderline ovarian cancer risk in exposed vs. unexposed was elevated but compatible with chance. Based on mothers' reports, diethylstilbestrol exposure did not increase the risk of overall or other cancers in third-generation females. Overall cancer risk in exposed males appeared elevated but compatible with chance. Testicular cancer risk was not elevated in exposed males, and there were no prostate cancers reported. These data do not provide evidence that diethylstilbestrol is associated with cancer risk in third-generation females or males. The third generation is relatively young and requires follow-up to assess risk as the cohort ages. Background: Females exposed prenatally to diethylstilbestrol (DES) have an elevated risk of cervical dysplasia, breast cancer, and clear cell adenocarcinoma (CCA) of the cervix/vagina. Testicular cancer risk is increased in prenatally exposed males. Epigenetic changes may mediate the transmission of DES effects to the next ("third") generation of offspring. Methods: Using data self-reported by third-generation females, we assessed DES in relation to the risk of cancer and benign breast and reproductive tract conditions. Using data from prenatally DES-exposed and unexposed mothers, we assessed DES in relation to cancer risk in their female and male offspring. Cancer risk was assessed by standardized incidence ratios (SIR) and 95% confidence intervals (CI); the risks of benign and malignant diagnoses were assessed by hazard ratios (HR) and 95% CI. Results: In self-reported data, DES exposure was not associated with an increased risk of overall cancer (HR 0.83; CI 0.36–1.90), breast cancer, or severe cervical dysplasia. No females reported CCA. The risk of borderline ovarian cancer appeared elevated, but the HR was imprecise (3.46; CI 0.37–32.42). Based on mothers' reports, DES exposure did not increase the risk of overall cancer (HR 0.80; CI 0.49–1.32) or of other cancers in third-generation females. Overall cancer risk in exposed males appeared elevated (HR 1.41; CI 0.70–2.86), but the CI was wide. The risk of testicular cancer was not elevated in exposed males; no cases of prostate cancer were reported. Conclusions: To date, there is little evidence that DES is associated with cancer risk in third-generation females or males, but these individuals are relatively young, and further follow-up is needed. [ABSTRACT FROM AUTHOR]

Simple Summary: The introduction of direct-acting antivirals (DAAs) has significantly improved the treatment of Hepatitis C, achieving high success rates and reducing complications and deaths. Despite their success, there are concerns about the potential risk of developing liver tumors after DAA treatment. This study analyzed data from the Swiss Hepatitis C Cohort to compare the risk of liver tumors and death among patients treated with DAAs, those treated with interferon (IFN)-based therapy, and untreated patients. The findings suggest that, while DAAs reduce the risk of death and do not increase the risk of non-liver tumors, there is a higher risk of liver tumors in patients treated with DAAs compared with untreated patients. This highlights the importance of ongoing liver cancer screening for patients who have undergone DAA treatment. Introduction: The use of direct-acting antivirals (DAAs) has drastically changed the management of HCV-infected patients by achieving a 95–98% sustained virologic response (SVR) and reducing morbidity and mortality in this population. However, despite their effectiveness, controversy exists concerning the occurrence of oncologic events following DAA therapy. Aims and Methods: A retrospective analysis was conducted on data from the Swiss Hepatitis C Cohort Study, a prospective cohort involving patients with positive HCV viremia upon inclusion, enrolled in various Swiss centers from September 2000 to November 2021. To examine potential differences in the risk of intrahepatic tumor (IHT) occurrence and death among patients treated with direct-acting antivirals (DAAs), untreated patients, and those receiving interferon (IFN)-based therapy, a semiparametric competing risk proportional hazards regression model was used. Results: Among 4082 patients (63.1% male, median age 45 years; genotype 1: 54.1%; cirrhosis: 16.1%), 1026 received exclusive treatment with IFN-based regimens, and 1180 were treated solely with DAAs. Over a median follow-up of 7.8 years (range: 3.8–11.9), 179 patients (4.4%) developed intrahepatic tumors (IHT), and 168 (4.1%) experienced extrahepatic tumors (EHT). The 5-year cumulative incidence of IHT was 1.55% (95% CI 0.96–2.48) for IFN-based therapy, 4.27% (95% CI 2.93–6.2) for DAA and 0.89% (95% CI 0.4–1.99) for untreated patients. There was no statistically significant difference in the risk of developing IHT (HR = 1.34; 95% CI = [0.70; 2.58]; p = 0.380) or death (HR = 0.66; 95% CI = [0.43; 1.03]; p = 0.066) between patients treated with DAAs and those treated with IFN. Conclusions: The DAAs reduced the risk of death and were not associated with an increased risk of extrahepatic tumors (EHT). In the adjusted model, accounting for cirrhosis and high liver stiffness, the DAA treatment was associated with a higher risk of IHT occurrence compared with untreated patients, emphasizing the relevance of implementing standardized hepatocellular carcinoma (HCC) screening post-DAA treatment. [ABSTRACT FROM AUTHOR]

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

Simple Summary: After failing the first-line treatment of high-risk non-muscle invasive urothelial carcinoma (NMIUC), salvage intravesical therapies are important to preserve patient quality of life and avoid radical surgery. However, some patients will develop a disease resistant to commonly used drug regimens. We aimed to evaluate a novel combinatory therapy consisting of intravesical sequential gemcitabine and cabazitaxel with concomitant systemic pembrolizumab (GCP) for patients with recurrent high-risk NMIUC of the bladder and upper urinary tracts. We found in a population of 26 patients with 31 treated units (bladder and/or upper urinary tracts) that, following GCP treatment, over half of the treated units remained disease-free at 2 years. In this highly pretreated population, the progression of disease was a concern with an estimated 30% rate of progression at 2 years. However, only 4% of the population experienced cancer-related death during this same time. Lastly, this regimen was well tolerated, with all patients completing the scheduled induction course. Growing evidence suggests that many patients with high-risk non-muscle invasive urothelial carcinoma (NMIUC) can undergo bladder-sparing management with salvage intravesical therapies. However, inherent or developed disease resistance, particularly after multiple lines of prior salvage therapy, implores the continued pursuit of new treatment combinations. Herein, we describe the outcomes of 26 patients (31 treated units; 24 lower tract, 7 upper tract) with high-risk NMIUC treated with sequential intravesical gemcitabine and cabazitaxel with concomitant intravenous pembrolizumab (GCP) at the University of Iowa from August 2020 to February 2023. Median (IQR) follow-up was 30 (IQR: 17–35) months. Treated units had a history of high-risk NMIUC with a median of four prior endoluminal inductions. Overall, 87% of units presented with CIS or positive urine cytology. The 1- and 2-year recurrence-free survival was 77% (CI: 58–88%) and 52% (CI: 30–70%), respectively. The 2-year progression-free and cancer-specific survival was 70% (CI: 44–85%) and 96% (CI: 75–99%), respectively. In total, 22/26 (85%) patients reported any adverse event and 5/26 (19%) reported a grade ≥3 adverse event; however, all patients tolerated a full induction course. These results suggest that GCP is an effective and tolerable treatment option for patients with recurrent high-risk NMIUC. [ABSTRACT FROM AUTHOR]

Simple Summary: Triple-negative breast cancer (TNBC) is a challenging form of breast cancer known for its aggressive nature and limited treatment options. The DESTINY-Breast 04 trial has demonstrated improved survival outcomes in metastatic human epithelial growth factor receptor 2 (HER2)-low breast cancer patients treated with trastuzumab-deruxtecan (T-Dxd). Since the potential proportion of breast cancer patients that may benefit from these novel agents are reported to be around 39% to 79%, investigating the role of HER2-low has been a topic of interest. By analyzing the outcomes of over 2500 patients, we discovered that those with HER2-low TNBC typically experience better survival rates than HER2-0 TNBC. This difference was especially significant in postmenopausal women. These findings suggest a potential re-evaluation of how TNBC is classified and treated, highlighting the importance of identifying HER2-low expression for improving personalized treatment strategies and patient care. TNBC is noted for its aggressive behavior and poor prognosis. Recently developed HER2 target agents have shown potential benefit even in HER2-low expressing breast cancers. This study retrospectively analyzed 2542 non-metastatic TNBC patients from 2008 to 2020, revealing that 26.0% were HER2-low. Data on demographics, tumor characteristics, pathologic complete response (pCR) rates and disease-free survival (DFS), distant metastasis-free survival (DMFS), overall survival (OS), and breast cancer-specific survival (BCSS) were analyzed. The HER2-low group, compared to the HER2-0 group, showed significantly better DFS, DMFS, OS, BCSS (p = 0.0072, p = 0.0096, p = 0.0180, and p = 0.0001, respectively) with older age and higher rates of postmenopausal status (p < 0.0001). No significant differences in pCR rates were observed. Multivariate analyses identified HER2 status as a significant prognostic factor for DFS (p = 0.048), DMFS (p = 0.018), OS (p = 0.049), and BCSS (p = 0.008). Subgroup analysis revealed that these effects varied with menopausal status, showing more pronounced benefits in postmenopausal women. Our findings suggest that HER2-low TNBC patients exhibit a distinct clinical profile and improved survival compared to HER2-0 TNBC patients, especially in postmenopausal patients. Further research on estrogen and HER2 interaction is needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic castration-resistant prostate cancer (mCRPC) represents a lethal stage of prostate cancer, characterized for its resistance to androgen deprivation therapy and variable survival outcomes. This study investigates how the composition of specific immune cells in the blood affects the prognosis of mCRPC patients who have not yet received chemotherapy. In looking at blood samples taken before treatment with the drug enzalutamide, we discovered significant correlations between lower levels of CD8 T cells and higher levels of monocytes, which were consistently linked to poorer survival rates. The prognostic value of blood CD8 T cells was independently validated in multivariate prognostic models and in an independent cohort of mCRPC patients. This study highlights the feasibility of blood immune-cell profiling in patients included in clinical trials and the association of blood CD8 T cells with the prognosis for mCRPC patients. The prognosis for patients with metastatic castration-resistant prostate cancer (mCRPC) varies, being influenced by blood-related factors such as transcriptional profiling and immune cell ratios. We aimed to address the contribution of distinct whole blood immune cell components to the prognosis of these patients. This study analyzed pre-treatment blood samples from 152 chemotherapy-naive mCRPC patients participating in a phase 2 clinical trial (NCT02288936) and a validation cohort. We used CIBERSORT-X to quantify 22 immune cell types and assessed their prognostic significance using Kaplan–Meier and Cox regression analyses. Reduced CD8 T-cell proportions and elevated monocyte levels were substantially connected with a worse survival. High monocyte counts correlated with a median survival of 32.2 months versus 40.3 months for lower counts (HR: 1.96, 95% CI 1.11–3.45). Low CD8 T-cell levels were associated with a median survival of 31.8 months compared to 40.3 months for higher levels (HR: 1.97, 95% CI 1.11–3.5). These findings were consistent in both the trial and validation cohorts. Multivariate analysis further confirmed the independent prognostic value of CD8 T-cell counts. This study highlights the prognostic implications of specific blood immune cells, suggesting they could serve as biomarkers in mCRPC patient management and should be further explored in clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: The 18F-FDG PET parameters reflecting the intensity and distribution of glucose uptake by the tumor are associated with prognosis in non-small-cell lung cancer (NSCLC) patients. We developed and evaluated an imaging-based model utilizing these 18F-FDG PET-derived features for predicting the five-year survival in NSCLC patients after curative surgery. The PET-based risk score constructed using the LASSO logistic method outperformed the predictive performances of individual 18F-FDG PET parameters. The PET-based risk score was an independent prognostic factor for clinical variables. Additionally, it demonstrated better predictive performance when combined with clinical variables. The FDG PET-based imaging model could aid in risk stratification for personalized adjuvant treatment and follow-up management of NSCLC patients after surgery. The aim of our retrospective study is to develop and assess an imaging-based model utilizing 18F-FDG PET parameters for predicting the five-year survival in non-small-cell lung cancer (NSCLC) patients after curative surgery. A total of 361 NSCLC patients who underwent curative surgery were assigned to the training set (n = 253) and the test set (n = 108). The LASSO regression model was used to construct a PET-based risk score for predicting five-year survival. A hybrid model that combined the PET-based risk score and clinical variables was developed using multivariate logistic regression analysis. The predictive performance was determined by the area under the curve (AUC). The individual features with the best predictive performances were co-occurrence_contrast (AUC = 0.675) and SUL peak (AUC = 0.671). The PET-based risk score was identified as an independent predictor after adjusting for clinical variables (OR 5.231, 95% CI 1.987–6.932; p = 0.009). The hybrid model, which integrated clinical variables, significantly outperformed the PET-based risk score alone in predictive accuracy (AUC = 0.771 vs. 0.696, p = 0.022), a finding that was consistent in the test set. The PET-based risk score, especially when integrated with clinical variables, demonstrates good predictive ability for five-year survival in NSCLC patients following curative surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Perineural invasion (PNI) is the infiltration of cancer cells into peripheral nerves and is recognized as potential cancer metastasis. The presence of PNI has been extensively studied as a prognostic factor in head and neck squamous cell carcinoma (HNSCC) recently. The aim of this study was to quantitatively assess the prognostic value of PNI in HNSCC. From the results of the systematic review and meta-analysis, we confirmed that PNI is an independent prognostic factor in HNSCC. Specifically, HNSCC patients with PNI have worse survival, and are more likely to relapse locally, regionally, and distantly compared to those without PNI. We hope that these findings can serve as a basis for consideration of PNI as an indicator for more advanced pathological stages and more intensive clinical management for HNSCC patients. The aim of this study was to conduct a comprehensive review of the predictive significance of PNI in HNSCC survival outcomes. A systematic search was conducted across multiple databases, and all studies published in the last decade were screened (Research Registry ID: reviewregistry1853). The included studies were assessed using the Quality in Prognosis Studies tool. Survival outcome data were extracted, combined, and presented as hazard ratios (HR) with a 95% confidence interval (CI). Totally, 74 studies encompassing 27,559 patients were analyzed and revealed a cumulative occurrent rate of 30% for PNI in HNSCC. PNI+ HNSCC patients had a worse overall survival (HR: 1.91, 95% CI: 1.71–2.13), disease-specific survival (HR: 1.79, 95% CI: 1.55–2.07), disease-free survival (HR: 1.82, 95% CI: 1.69–1.96), local recurrence (HR: 2.54, 95% CI: 1.93–3.33), locoregional recurrence (HR: 2.27, 95% CI: 1.82–2.82), locoregional relapse free survival (HR: 1.77, 95% CI: 1.28–2.45), distant metastasis (HR: 1.82, 95% CI: 1.34–2.48), and distant metastasis-free survival (HR: 2.97, 95% CI: 1.82–4.85) compared to those PNI– patients. The available evidence unequivocally establishes PNI as a critical prognostic factor for worse survival in HNSCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This study examines the validity of the NETest, a blood biomarker, in patients with small intestinal neuroendocrine neoplasms (Si-NENs). Two groups were studied: those with metastatic Si-NENs (Group 1) and those without macroscopic disease, post-operatively (Group 2). In Group 1, results showed that NETest scores were associated with progression-free survival (PFS) and overall survival (OS) in metastatic Si-NENs. Factors including tumour growth rate (TGR), elevated chromogranin A (CgA) levels, and presence of lung metastases were also predictive of PFS or OS. In Group 2, NETest monitoring after surgery may have potential in helping to predict early local or metastatic disease recurrence. This study suggests potential benefits of using NETest alongside other predictors for Si-NEN management. Further research with longer follow-up periods is needed to confirm the utility of the NETest. Current biomarkers do not adequately predict the behaviour of neuroendocrine neoplasms (NENs). This study assessed the NETest, a multianalyte blood biomarker, in patients with small intestinal NENs (Si-NENs). We studied two patient groups: Group 1: metastatic Si-NENs (n = 102) and Group 2: post-operatively disease-free according to 68Ga-DOTATATE PET (n = 16). NETest scores were ≤20% (normal), 21–40% (low), 41–79% (intermediate), or ≥80% (high). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan–Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. In Group 1, the median NETest score was 40% (IQR: 33.3–46.7%). The NETest value (HR: 1.032, 95% CI: 1.003–1.062, p = 0.033) and high-risk NETest category (HR: 10.5, 95% CI: 1.35–81.7, p = 0.025) were independent predictors of PFS, along with presence of lung metastases, CgA levels > 10 × ULN, and tumour growth rate (TGR). Independent predictors of OS were the NETest value (HR: 1.035, 95% CI: 1.005–1.066, p = 0.024) and high-risk NETest category (HR: 15.2, 95% CI: 1.52–151, p = 0.02), along with presence of lung metastases and CgA levels > 10 × ULN. In Group 2, ROC analysis identified an AUC of 0.909 (95% CI: 0.75–0.100) for prediction of local or metastatic recurrence. Blood NETest scores were associated with PFS and OS in patients with metastatic Si-NENs, along with TGR, CgA > 10 × ULN, and presence of lung metastases. [ABSTRACT FROM AUTHOR]

Simple Summary: Thymic neuroendocrine tumors (Th-NETs) are rare, with limited research on prognostic markers and treatments. Our retrospective study evaluated clinicopathological characteristics and therapeutic strategies for Th-NETs, filling gaps in existing studies. We highlighted the importance of biomarkers such as serum neuron-specific enolase, inflammatory factors, and oxygen 6-methylguanine-DNA methyltransferase, as well as the roles of surgical interventions, postoperative therapies, and temozolomide-based chemotherapy in improving patient survival. Our findings confirmed the crucial role of surgical treatment and the potential benefits of postoperative adjuvant radiotherapy. Furthermore, temozolomide-based chemotherapy demonstrated efficacy in Th-NETs treatment, with the neutrophil-to-lymphocyte ratio and serum neuron-specific enolase proving to be valuable prognostic markers necessitating further research. Background: Thymic neuroendocrine tumors (Th-NETs) are rare and aggressive, with a scarcity of research on predicting patient prognosis. Our study aimed to assess the impact of prognostic markers and temozolomide (TMZ)-based chemotherapy on survival in Th-NETs. Methods: We retrospectively reviewed the medical records of patients diagnosed with Th-NETs between 2013 and 2023 at our institution. We collected clinicopathological data, including tumor pathological grading, staging, serum concentrations of neuron-specific enolase (NSE) and pro-gastrin-releasing peptide, levels of inflammatory factors, and expression of oxygen 6-methylguanine-DNA methyltransferase (MGMT). Treatment details (such as surgery and chemotherapy) and survival outcomes were also documented. Results: A total of 32 patients were included in our study after excluding those without complete available information. The median progression-free survival (PFS) was 12.5 months (95%CI, 8–16 months) for 19 patients who received TMZ-based chemotherapy. Twenty-one patients underwent surgery as the primary treatment, demonstrating a median disease-free survival (DFS) of 51.0 months. The inflammatory factor neutrophil-to-lymphocyte ratio (NLR) was an independent prognostic indicator of DFS in postoperative patients and PFS in TMZ-treated patients. The overall 3-, 5-, and 10-year survival rates were 86.6%, 69.5%, and 33.8%, respectively. Ki67 level exceeding 10% (p = 0.048) and absence of surgical resection (p = 0.003) were significantly associated with worse overall survival (OS). Conclusion: Surgical treatment was currently the primary method for treating Th-NETs, and postoperative adjuvant therapy was an essential consideration for specific patient cohorts. Despite widespread positive MGMT expression, TMZ-based chemotherapy showed promise. Some potential prognostic biomarkers such as NLR and NSE need more attention. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to determine the risk and rate of development of overall and site-specific cancer in patients with type 2 diabetes mellitus compared with non-diabetic individuals. In this retrospective cohort study, excess incidence of cancer was found in patients with type 2 diabetes mellitus. While the incidence of cancer decreased in non-diabetic controls between 2015 and 2019 in most age groups and for several cancer sites, this decrease was less significant among patients with type 2 diabetes mellitus. Therefore, the results of this study demonstrate that the presence of type 2 diabetes mellitus leads to a higher incidence of cancer. (1) Background: Among the chronic complications of type 2 diabetes mellitus, cancer has become the leading cause of death in several countries. Our objective was to determine whether prevalent type 2 diabetes mellitus is associated with a higher incidence of cancer. (2) Methods: This study comprised a nationwide analysis conducted in Hungary. The study population was divided into two groups: a type 2 diabetes mellitus group vs. a non-diabetic group. The primary outcome was the risk related to overall cancer incidence; a key secondary outcome was the overall incidence of cancer in distinct study years; and a further outcome was the annual percent changes. (3) Results: The odds ratio related to the overall incidence of cancer was 2.50 (95% confidence interval: 2.46–2.55, p < 0.0001) in patients with diabetes as related to non-diabetic controls. The odds ratio was higher in males than in females [ORmales: 2.76 (2.70–2.82) vs. ORfemales: 2.27 (2.22–2.33), p < 0.05 for male-to-female comparison]. The annual cancer incidence rate declined in non-diabetic controls, but not in patients with diabetes [−1.79% (−2.07–−1.52%), p < 0.0001] vs. −0.50% (−1.12–+0.10%), p = 0.0991]. Several types of cancer showed a decreasing tendency in non-diabetic controls, but not in patients with type 2 diabetes. (4) Conclusions: Type 2 diabetes is associated with a higher risk of cancer. While the cancer incidence decreased for non-diabetic individuals with time, it remained unchanged in patients with T2DM. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer remains a prevalent neoplasm affecting both genders. Despite advancements in screening techniques facilitating early detection, effective patient management remains paramount. This study investigates the impact of a multidisciplinary team (MDT) approach on patient outcomes. Results reveal a significant improvement in survival rates among MDT-followed patients compared to those lacking MDT oversight. Notably, no-MDT patients exhibited a twofold increase in mortality risk from both colon and rectal cancers. Furthermore, advanced age (>70 years) and advanced-stage disease (III and IV) emerged as pivotal risk factors. Consequently, prioritizing MDT intervention for these high-risk cohorts is imperative to optimize therapeutic strategies. Colorectal cancer emerged as the third most prevalent malignancy worldwide, affecting nearly 2 million individuals in the year 2020. This study elucidates the pivotal role of a multidisciplinary team (MDT) in influencing the prognosis, as measured by relative survival rates, depending upon the stage and age. Cases recorded in an Italian Cancer Registry between 2017 and 2018 were included. Relative survival was reported at 1 and 3 years after diagnosis comparing MDT vs. no-MDT approaches. During the study period, 605 CRCs were recorded while 361 (59.7%) were taken care of by an MDT. Compared to no-MDT, MDT patients were younger with earlier stages and received more surgery. One year after diagnosis, survival was 78.7% (90% in MDT vs. 62% in no-MDT); stratifying by stage, in the MDT group there was no survival advantage for stage I (97.2% vs. 89.9%) and II (96.8% vs. 89.4%), but an advantage was observed for stage III (86.4% vs. 56.9%) and stage IV (63.7% vs. 27.4%). Similar values were observed at 3 years where a marked advantage was observed for stages III (69.9% vs. 35.1%) and IV (29.2% vs. 5.1%). The univariable analysis confirmed an excess risk in the no-MDT group (HR 2.6; 95% CI 2.0–3.3), also confirmed in the multivariable regression analysis (HR 2.0; 95% CI 1.5–2.5). Despite the increase in the number of MDT patients in 2018 (from 50% to 69%), this does not correspond to an improvement in outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: Given the low incidence, heterogeneous behavior, and diverse anatomical sites of salivary gland cancer (SGC), there are a limited number of clinical studies on its management. This is the first systematic review and meta-analysis to report the cumulative evidence on postoperative radiotherapy (PORT) for SGC of the head and neck. Based on 2962 patients with SGC from 26 studies, this study demonstrated the long-term survival and toxicities of PORT as a local treatment modality for SGC. Considering the suboptimal disease-free survival and distant metastasis-dominant recurrent patterns, however, an intensified treatment strategy is needed. Background: Because of the rarity, heterogeneous histology, and diverse anatomical sites of salivary gland cancer (SGC), there are a limited number of clinical studies on its management. This study reports the cumulative evidence of postoperative radiotherapy (PORT) for SGC of the head and neck. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases between 7th and 10th November 2023. Results: A total of 2962 patients from 26 studies between 2007 and 2023 were included in this meta-analysis. The median RT dose was 64 Gy (range: 56–66 Gy). The median proportions of high-grade, pathological tumor stage 3 or 4 and pathological lymph node involvement were 42% (0–100%), 40% (0–77%), and 31% (0–75%). The pooled locoregional control rates at 3, 5, and 10 years were 92% (95% confidence interval [CI], 89–94%), 89% (95% CI, 86–93%), and 84% (95% CI, 73–92%), respectively. The pooled disease-free survival (DFS) rates at 3, 5, and 10 years were 77% (95% CI, 70–83%), 67% (95% CI, 60–74%), and 61% (95% CI, 55–67%), respectively. The pooled overall survival rates at 3, 5, and 10 years were 84% (95% CI, 79–88%), 75% (95% CI, 72–79%), and 68% (95% CI, 62–74%), respectively. Severe late toxicity ≥ grade 3 occurred in 7% (95% CI, 3–14%). Conclusion: PORT showed favorable long-term efficacy and safety in SGC, especially for patients with high-grade histology. Considering that DFS continued to decrease, further clinical trials exploring treatment intensification are warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer is the leading cause of cancer-related deaths in the United States, and people with Type 2 Diabetes often use insulin therapy, which has been associated with increased lung cancer risk. This study explores whether non-insulin diabetes medications can lower this risk compared to insulin. By analyzing medical records from over a million patients, the researchers aim to identify which medications are associated with a reduced risk of lung cancer compared with insulin. The results could help providers select treatments that not only manage blood sugar but also minimize lung cancer risk, leading to better patient outcomes and informing future treatment guidelines. Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), is associated with increased LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients, comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed the de-identified electronic health records of 1,040,341 T2DM patients treated between 2005 and 2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, were associated with significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk. [ABSTRACT FROM AUTHOR]

Simple Summary: Prior research has identified various prognostic markers in epithelial ovarian cancer (EOC), including BRCA mutation status and a response to platinum-based chemotherapy, to predict outcomes in patients undergoing PARP inhibitor maintenance therapy. The role of CA-125 elimination rate constant K (KELIM), although recognized as a prognostic indicator, has not been fully investigated. This study underscores the prognostic significance of KELIM, revealing that a favorable KELIM score significantly correlates with better PFS in patients treated with primary cytoreductive surgery (PCS) followed by PARP inhibitor therapy. It also shows that KELIM's predictive value varies with the timing of surgery, extending a different view of its utility in real-world practice. KELIM could be integrated into clinical decision-making processes, potentially informing future clinical guidelines and research into optimal treatment strategies for targeted use of PARP inhibitors in advanced EOC patients. Background: This multicenter retrospective study aimed to investigate the prognostic value of the CA-125 elimination rate constant K (KELIM) in EOC patients who received platinum-based chemotherapy followed by PARP inhibitors, in either upfront or interval treatment settings. Methods: Between July 2019 and November 2022, we identified stage III–IV EOC patients who underwent primary or interval cytoreductive surgery and received olaparib or niraparib. Individual KELIM values were assessed based on validated kinetics and classified into favorable and unfavorable cohorts. Results: In a study of 252 patients undergoing frontline maintenance therapy with olaparib or niraparib, favorable KELIM (≥1) scores were associated with a higher PFS benefit in the primary cytoreductive surgery (PCS) cohort (hazard ratio (HR) for disease progression or death 3.51, 95% confidence interval (CI); 1.37–8.97, p = 0.009). Additionally, within the interval cytoreductive surgery (ICS) cohort, a favorable KELIM score (≥1) significantly increased the likelihood of achieving complete resection following cytoreductive surgery, with 59.4% in the favorable KELIM group compared to 37.8% in those with unfavorable KELIM. Conclusions: A favorable KELIM score was associated with improved PFS in patients with advanced EOC undergoing PCS. Furthermore, in the ICS cohort, a favorable KELIM score increased the probability of complete cytoreduction. [ABSTRACT FROM AUTHOR]

Simple Summary: KRAS is one of the most prominent driver genes implicated in colorectal cancer (CRC), with mutations detected in 33% to 50% of CRC patients. Exon 2 harbors up to 98% of these mutations. Variants in this gene play crucial roles in the progression of the disease, influencing its development, clinical manifestations, and treatment election. This study elucidates a 17% prevalence of mutations in KRAS exon 2 among western Mexican patients with sporadic CRC. Furthermore, a 30% pooled prevalence of mutations in KRAS exon 2 was determined after analyzing an additional 16 studies from Latin America, encompassing 12,604 CRC patients. Due to advances in precision medicine treatments, knowing the pathogenic status of the KRAS gene will become imperative to optimally select targeted therapies. We searched for the prevalence of actionable somatic mutations in exon 2 of the KRAS gene in western Mexican patients with CRC. Tumor tissue DNA samples from 150 patients with sporadic CRC recruited at the Civil Hospital of Guadalajara were analyzed. Mutations in exon 2 of the KRAS gene were identified using Sanger sequencing, and the data were analyzed considering clinical–pathological characteristics. Variants in codon 12 (rs121913529 G>A, G>C, and G>T) and codon 13 (rs112445441 G>A) were detected in 26 patients (with a prevalence of 17%). No significant associations were found between these variants and clinical–pathological characteristics (p > 0.05). Furthermore, a comprehensive search was carried out in PubMed/NCBI and Google for the prevalence of KRAS exon 2 mutations in Latin American populations. The 17 studies included 12,604 CRC patients, with an overall prevalence of 30% (95% CI = 0.26–0.35), although the prevalence ranged from 13 to 43% across the different data sources. Determining the variation and frequency of KRAS alleles in CRC patients will enhance their potential to receive targeted treatments and contribute to the understanding of the genomic profile of CRC. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with diabetes are at greater risk of developing liver cancer than the general population. However, risk prediction models or scoring systems for liver cancer mostly focus on patients with preexisting liver diseases, and models for patients with diabetes or those in the absence of liver diseases remain rare. This study aims to develop a risk scoring system among diabetes patients and a sub-model for diabetes patients without cirrhosis or chronic viral hepatitis. In the final model, presence of chronic hepatitis B/C, cirrhosis, alanine aminotransferase, age, and sex were included as predictors. In the sub-model, alanine aminotransferase, triglycerides, age, and sex were included as predictors. Findings of the study may potentially provide individualized risk prediction for diabetes patients. Background: Most liver cancer scoring systems focus on patients with preexisting liver diseases such as chronic viral hepatitis or liver cirrhosis. Patients with diabetes are at higher risk of developing liver cancer than the general population. However, liver cancer scoring systems for patients in the absence of liver diseases or those with diabetes remain rare. This study aims to develop a risk scoring system for liver cancer prediction among diabetes patients and a sub-model among diabetes patients without cirrhosis/chronic viral hepatitis. Methods: A retrospective cohort study was performed using electronic health records of Hong Kong. Patients who received diabetes care in general outpatient clinics between 2010 and 2019 without cancer history were included and followed up until December 2019. The outcome was diagnosis of liver cancer during follow-up. A risk scoring system was developed by applying random survival forest in variable selection, and Cox regression in weight assignment. Results: The liver cancer incidence was 0.92 per 1000 person-years. Patients who developed liver cancer (n = 1995) and those who remained free of cancer (n = 1969) during follow-up (median: 6.2 years) were selected for model building. In the final time-to-event scoring system, presence of chronic hepatitis B/C, alanine aminotransferase, age, presence of cirrhosis, and sex were included as predictors. The concordance index was 0.706 (95%CI: 0.676–0.741). In the sub-model for patients without cirrhosis/chronic viral hepatitis, alanine aminotransferase, age, triglycerides, and sex were selected as predictors. Conclusions: The proposed scoring system may provide a parsimonious score for liver cancer risk prediction among diabetes patients. [ABSTRACT FROM AUTHOR]