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Background: Maintaining the dose-intensity of cancer treatment is an important prognostic factor of aggressive hematological malignancies. The objective of this study was to assess the long-term outcomes of intensive care unit (ICU) survivors with acute myeloid leukemia (AML) or aggressive B-cell non-Hodgkin lymphoma (B-NHL) with emphasis on the resumption of the intended optimal regimen of cancer treatment. Patients and methods: We conducted a retrospective (2013–2021) single-center observational study where we included patients with AML and B-NHL discharged alive from the ICU after an unplanned admission. The primary endpoint was the change in the intended optimal cancer treatment following ICU discharge. Secondary endpoints were 1-year progression-free survival and overall survival rates. Determinants associated with modifications in cancer treatment were assessed through multivariate logistic regression. Results: Over the study period, 366 patients with AML or B-NHL were admitted to the ICU, of whom 170 survivors with AML (n = 92) and B-NHL (n = 78) formed the cohort of interest. The hematological malignancy was recently diagnosed in 68% of patients. The admission Sequential Organ Failure Assessment (SOFA) score was 5 (interquartile range 4–8). During the ICU stay, 30 patients (17.6%) required invasive mechanical ventilation, 29 (17.0%) vasopressor support, and 16 (9.4%) renal replacement therapy. The one-year survival rate following ICU discharge was 59.5%. Further modifications in hematologic treatment regimens were required in 72 patients (42%). In multivariate analysis, age > 65 years (odds ratio (OR) 3.54 [95%-confidence interval 1.67–7.50], p < 0.001), ICU-discharge hyperbilirubinemia > 20 µmol/L (OR 3.01 [1.10–8.15], p = 0.031), and therapeutic limitations (OR 16.5 [1.83–149.7], p = 0.012) were independently associated with modifications in cancer treatment. Post-ICU modifications of cancer treatment had significant impact on in-hospital, 1-year overall survival and progression-free survival. Conclusion: The intended cancer treatment could be resumed in 58% of ICU survivors with aggressive hematological malignancies. At the time of ICU discharge, advanced age, persistent liver dysfunction and decisions to limit further life-support therapies were independent determinants of cancer treatment modifications. These modifications were associated with worsened one-year outcomes. [ABSTRACT FROM AUTHOR]

Objective: Cyclin-dependent kinase (CDK) 4 and 6 inhibitors (abemaciclib, palbociclib and ribociclib) have been recommended in the first-line treatment of hormone receptor-positive (HR+) breast cancer in China. Our study aims to evaluate the efficacy and safety of CDK4/6 inhibitors by processing survival data using fractional polynomial modeling methods. Methods: Phase II or III randomized controlled trials in treatment-naive HR + patients with advanced breast cancer were systematically searched through the preset search strategy. The fractional polynomial (FP) model was used to relax the proportional hazard assumption and obtain time-varying hazard ratio (HR). Progression-free life years (PFLYs) and life years (LYs) were calculated from the area under curve (AUC) of the predicted progression-free survival (PFS) and overall survival (OS) curves to evaluate the long-term efficacy benefit. Odds ratio (OR) of grade≥3 adverse events were analyzed for safety outcomes. Results: 6 randomized controlled trials with 2,638 patients were included. The first-order FP model (p = -1) and the first-order FP model (p = 1) were used to calculate the time-varying HR of PFS and OS, respectively. Extrapolating to 240 months, abemaciclib obtained a PFS benefit of 3.059 PFLYs and 6.275 LYs by calculating the AUC of the PFS and OS curves. Palbociclib obtained 2.302 PFLYs and 6.351 LYs. Ribociclib obtained 2.636 PFLYs and 6.543 LYs. In terms of safety, the use of CDK4/6 inhibitors resulted in a higher risk of adverse events (OR = 9.84, 95% CI: 8.13-11.95), especially for palbociclib (OR = 14.04, 95% CI: 10.52-18.90). Conclusion: The use of CDK4/6 inhibitors in treatment-naive patients with HR + advanced breast cancer significantly improves survival, but also increases the risk of adverse events. Abemaciclib and ribociclib may be the best options for prolonging PFS and OS in treatment-naïve patients, respectively. [ABSTRACT FROM AUTHOR]

Objectives: Pretreatment biomarkers are needed to identify patients with non‐small‐cell lung cancer (NSCLC) likely to have worse survival. This ensures that only patients with a real chance of benefit receive immune checkpoint inhibitor (ICI) treatment. In this study, we examined the associations of baseline nutritional and inflammatory biomarkers with overall survival in a real‐world cohort of NSCLC patients who received ICIs. Materials and Methods: We used prospectively collected data from the OncoLifeS data biobank. The cohort included 500 advanced‐stage NSCLC patients treated with ICIs from May 2015 to June 2021. Biomarkers were evaluated within 2 weeks before ICI treatment: neutrophil‐to‐lymphocyte ratio, C‐reactive protein (CRP), Glasgow prognostic score, CRP/albumin ratio (CAR), prognostic nutritional index (PNI), and advanced lung cancer inflammation index. For each biomarker, low‐ and high‐risk groups were defined using literature‐based cut‐offs. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were estimated using adjusted survival analysis. Results: Most patients were male (60.8%), the mean baseline age was 65 ± 9 years, and 88% had stage IV disease. For each biomarker, low‐risk patients had better overall survival (all, p < 0.001), with CAR and PNI showing the strongest associations. In multivariable analyses a combined CAR/PNI risk score had a stronger association with overall survival (aHR 3.09, 95% CI 2.36–4.06) than CAR alone (aHR 2.22, 95% CI 1.79–2.76) or PNI alone (aHR 2.09, 95% CI 1.66–2.61). Conclusion: These results highlight the potential value of nutritional and inflammatory biomarkers, in particular CAR and PNI, in identifying NSCLC patients with highest mortality risk before starting ICI treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explored how genetic changes influence treatment effectiveness and survival in patients with advanced pancreatic cancer. By examining tumors from 142 patients, researchers identified specific genetic mutations that can predict how well a patient responds to chemotherapy. Findings showed that mutations in certain genetic pathways are associated with longer survival and better treatment outcomes. This research highlights the importance of tailoring cancer treatment based on individual genetic profiles, potentially leading to more personalized and effective therapies for pancreatic cancer patients. (1) Background: Pancreatic ductal adenocarcinoma (PDAC) has low survival rates despite treatment advancements. Aim: This study aims to show how molecular profiling could possibly guide personalized treatment strategies, which may help improve survival outcomes in patients with PDAC. (2) Materials and Methods: A retrospective analysis of 142 PDAC patients from a single academic center was conducted. Patients underwent chemotherapy and next-generation sequencing for molecular profiling. Key oncogenic pathways were identified using the Reactome pathway database. Survival analysis was performed using Kaplan–Meier curves and Cox Proportional Hazards Regression. (3) Results: Patients mainly received FOLFIRINOX (n = 62) or gemcitabine nab-paclitaxel (n = 62) as initial chemotherapy. The median OS was 13.6 months. Longer median OS was noted in patients with NOTCH (15 vs. 12.3 months, p = 0.007) and KIT pathway mutations (21.3 vs. 12.12 months, p = 0.04). Combinatorial pathway analysis indicated potential synergistic effects on survival. In the PFS, PI3K pathway (6.6 vs. 5.7 months, p = 0.03) and KIT pathway (10.3 vs. 6.2 months, p = 0.03) mutations correlated with improved PFS within the gemcitabine nab-paclitaxel subgroup. (4) Conclusions: Molecular profiling could play a role in PDAC for predicting outcomes and responses to therapies like FOLFIRINOX and gemcitabine nab-paclitaxel. Integrating genomic data into clinical decision-making can benefit PDAC treatment, though further validation is needed to fully utilize precision oncology in PDAC management. [ABSTRACT FROM AUTHOR]

Simple Summary: Response to treatment and prognosis after 223Ra treatment varies among patients. Using a combination of clinical, biochemical, and radiomic data from bone scintigraphy and 18F-Fluorocholine PET/CT obtained from our prospective ChoPET-Rad study, we identified predictive and prognostic variables. The goal was to create a nomogram able to predict therapeutic failure and overall survival, aiding in the selection of more suitable candidates for this treatment. Purpose: We aimed to develop a nomogram able to predict treatment failure, skeletal events, and overall survival (OS) in patients with castration-resistant prostate cancer with bone metastases (CRPC-BM) treated with Radium-223 dichloride (223Ra). Patients and Methods: Patients from the Castilla-La Mancha Spanish region were prospectively included in the ChoPET-Rad multicenter study from January 2015 to December 2022. Patients underwent baseline, interim, and end-of-treatment bone scintigraphy (BS) and 18F-Fluorocholine PET/CT (FCH PET/CT) scans, obtaining multiple imaging radiomics as well as clinical and biochemical variables during follow-up and studying their association with the previously defined end-points. Survival analysis was performed using the Kaplan–Meier method and Cox regression. Multivariate logistic and Cox regression models were calculated, and these models were depicted by means of nomograms. Results: Median progression-free survival (PFS) and OS were 4 and 14 months (mo), respectively. The variables that showed independent and significant association with therapeutic failure were baseline alkaline phosphatase (AP) levels (p = 0.022) and the characteristics of BM on the CT portion of PET/CT (p = 0.017). In the case of OS, the significant variables were therapeutic failure (p = 0.038), the number of lines received after 223Ra (p < 0.001), average SUVmax (p = 0.002), bone marrow infiltration in FCH PET/CT (p = 0.006), and interim FCH PET/CT response (p = 0.048). Final nomograms included these variables, showing good discrimination among the 100 patients included in our study. In the study of skeletal events, only OS showed a significant association in the multivariate analysis, resulting in an inconsistent nomogram design. Conclusions: FCH PET/CT appears to be a good tool for evaluating patients eligible for treatment with 223Ra, as well as for their follow-up. Thus, findings derived from it, such as the morphological characteristics of BM in the CT, bone marrow infiltration, or the response to 223Ra in the interim study, have proven to be solid and useful variables in the creation of nomograms for predicting therapeutic failure and OS. [ABSTRACT FROM AUTHOR]

Simple Summary: Tertiary lymphoid structures (TLS) arise in non-lymphoid tissues due to inflammation or cancer and play a key role in adaptive immune responses. In this study, we analyzed the TLS maturity in 78 patients with pathological T4 colorectal cancer (CRC). Mature TLS, identified by organized T (CD3+) and B (CD20+) lymphocytes with Ki-67-positive B cells, have been linked to microsatellite instability and improved cancer-specific and post-recurrence survival. High tumor Ki-67 expression correlated with poorer outcomes. The absence of mature TLS independently predicted poor survival. Tumors with mature TLS showed a higher infiltration of CD3+ T cells, FOXP3+ T cells, and CD86+ immune cells, including M1-like macrophages. Focusing on the Ki-67 expression pattern, the simultaneous evaluation of TLS maturity and tumor proliferation potency is suggested to be a potential prognostic indicator in CRC. Tertiary lymphoid structures (TLSs) are complex lymphocyte clusters that arise in non-lymphoid tissues due to inflammation or cancer. A mature TLS with proliferating germinal centers is associated with a favorable prognosis in various cancers. However, the effect of TLS maturity on advanced colorectal cancer (CRC) remains unexplored. We analyzed the significance of TLS maturity and tumor Ki-67 expression in surgically resected tumors from 78 patients with pathological T4 CRC. Mature TLS was defined as the organized infiltration of T and B cells with Ki-67-positive proliferating germinal centers. We analyzed the relationship between TLS maturity and intratumoral immune cell infiltration. Mature TLS with germinal center Ki-67 expression was associated with microsatellite instability and improved survival; however, high tumor Ki-67 expression was associated with poor survival in the same cohort. Multivariate analysis identified the absence of mature TLS as an independent predictor of poor post-recurrence overall survival. Intratumoral infiltration of T lymphocytes and macrophages was significantly elevated in tumors with mature TLS compared to those lacking it. High Ki-67 levels and absent mature TLS were identified as poor prognostic factors in advanced CRC. Mature TLS could serve as a promising marker for patients at high-risk of CRC. [ABSTRACT FROM AUTHOR]

Aim: The PREDICT tool is used to estimate survival in breast cancer patients according to the types of treatment given. This study aimed to assess the accuracy of the PREDICT tool and identify the prognostic factors for survival in patients with breast cancer. Material and Methods: A retrospective study was performed based on data collected from the Hospital Sultanah Nur Zahirah, Terengganu, Malaysia. All female patients diagnosed with stage I to IV breast cancer were identified from the year 2011 to 2017. Results: Based on data from 355 eligible patients, the predicted and observed 5-year overall survival rates were 75.8% and 75.2%, respectively. The model performed fairly well, with the area under the curve (AUC) of 0.747 (95% confidence interval (CI): 0.69-0.81) in the predicted 5-year overall survival. Among the 585 patients diagnosed with stage I to IV breast cancer, stage at the presentation (stage III hazard ratio (HR): 5.80, 95% CI: 1.69-19.94, p=0.005, stage IV HR: 10.61, 95% CI: 3.09-36.49, p<0.001), without surgical treatment (HR: 2.29, 95% CI: 1.73-3.00, p<0.001), without radiotherapy (HR: 1.92, 95% CI: 1.41-2.62, p<0.001), and without neoadjuvant chemotherapy (HR: 0.63, 95% CI: 0.47-0.86, p=0.003) were associated with death in breast cancer patients. Conclusion: The PREDICT tool accurately estimated the 5-year overall survival in the study center. It might serve as a useful prognostication tool during consultation. Late stages of the disease, patients without surgical treatment, and patients without radiotherapy were associated with a higher risk of death in breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: Male breast cancer (MBC) is a rare condition, and recent research has underscored notable distinctions between MBC and breast cancer in women. This study aimed to assess and contrast the long-term survival outcomes and disease patterns of MBC patients with those of their female counterparts. Methods: We analyzed data from 113,845 patients diagnosed with breast cancer who had undergone curative surgery from the Korean Breast Cancer Registry (KBCR) between January 1990 and August 2014 in Seoul, Korea. The five-year overall survival was analyzed according to clinicopathological characteristics. Results: Among 113,845 patients with breast cancer, 473 MBC cases were included. The median duration of follow-up was 72 months. The median age at diagnosis was 60 and 48 years for MBC and female breast cancer, respectively. Most male patients (92.6%) underwent total mastectomy, while 50.4% of female patients underwent breast-conserving surgery. Among MBC, 63.2% received chemotherapy, and 83.9% of hormone receptor-positive male patients received endocrine therapy. In survival analysis, MBC demonstrated distinct 5-year overall survival patterns compared with female breast cancer, according to age at diagnosis. In women with breast cancer, the younger age group (=40 years) demonstrated worse 5-year overall survival than did the older age group (>40 years) (91.3% vs 92.7%, p <0.05). While in MBC, the younger age group (=40 years) demonstrated better 5-year overall survival than did the older age group (>40 years) (97.4% vs 86.4%, p <0.05). Discussion: In conclusion within this extensive cohort, we have revealed unique survival patterns in MBC that diverge from those observed in women with breast cancer. This study enhances our comprehension of MBC prognosis and can potentially shed light on unresolved questions, paving the way for future research in the realm of MBC. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma (HNSCC) remains a global health concern due to the lack of precise early diagnostic biomarkers and often-delayed diagnosis. This study employs machine learning, weighted gene co-expression network analysis, and network biology to identify transcriptomic markers for HNSCC detection. We identified nine genes with significantly differentially expressed activity in samples from HNSCC patients. These gene signatures could greatly improve early HNSCC identification and warrant further investigation to confirm their predictive and therapeutic significance. The transcriptional landscape of platelets in head and neck cancer patients revealed distinct gene expression profiles compared to healthy controls, underscoring the systemic impact of the tumor on blood platelets. Additionally, the study emphasizes the role of tumor-educated platelets (TEPs), which carry RNA signatures indicative of tumor-derived material, offering a non-invasive source for early-detection biomarkers. Although there has been a reduction in head and neck squamous cell carcinoma occurrence, it continues to be a serious global health concern. The lack of precise early diagnostic biomarkers and postponed diagnosis in the later stages are notable constraints that contribute to poor survival rates and emphasize the need for innovative diagnostic methods. In this study, we employed machine learning alongside weighted gene co-expression network analysis (WGCNA) and network biology to investigate the gene expression patterns of blood platelets, identifying transcriptomic markers for HNSCC diagnosis. Our comprehensive examination of publicly available gene expression datasets revealed nine genes with significantly elevated expression in samples from individuals diagnosed with HNSCC. These potential diagnostic markers were further assessed using TCGA and GTEx datasets, demonstrating high accuracy in distinguishing between HNSCC and non-cancerous samples. The findings indicate that these gene signatures could revolutionize early HNSCC identification. Additionally, the study highlights the significance of tumor-educated platelets (TEPs), which carry RNA signatures indicative of tumor-derived material, offering a non-invasive source for early-detection biomarkers. Despite using platelet and tumor samples from different individuals, our results suggest that TEPs reflect the transcriptomic and epigenetic landscape of tumors. Future research should aim to directly correlate tumor and platelet samples from the same patients to further elucidate this relationship. This study underscores the potential of these biomarkers in transforming early diagnosis and personalized treatment strategies for HNSCC, advocating for further research to validate their predictive and therapeutic potential. [ABSTRACT FROM AUTHOR]

Simple Summary: This study describes a large-scale analysis of cancer metabolism across The Cancer Genome Atlas and Multiple Myeloma Research Foundation MMRF-COMMPASS study encompassing 10,915 patients from 34 different cancer types. To the best of our knowledge, this is the first such large-scale metabolic analysis performed using these data. Our approach identified biologically interpretable metabolic biomarkers of overall survival in 31 out of 34 cancer types evaluated. Additionally, in a subset of 7 cancer types, we predict chemosensitivity to antifolate-based therapies and a biomarker of response based on our patient-specific metabolic models. Finally, this work introduces the concept of "interpretation-driven biomarker identification". In this framework, biological interpretability of biomarker signatures is ensured first by using network-based simulations to characterize tumor biology, then using survival analysis to identify any biological features associated with overall survival—essentially decoupling biomarker discovery and biological interpretation of biomarker scores. Despite the high variability in cancer biology, cancers nevertheless exhibit cohesive hallmarks across multiple cancer types, notably dysregulated metabolism. Metabolism plays a central role in cancer biology, and shifts in metabolic pathways have been linked to tumor aggressiveness and likelihood of response to therapy. We therefore sought to interrogate metabolism across cancer types and understand how intrinsic modes of metabolism vary within and across indications and how they relate to patient prognosis. We used context specific genome-scale metabolic modeling to simulate metabolism across 10,915 patients from 34 cancer types from The Cancer Genome Atlas and the MMRF-COMMPASS study. We found that cancer metabolism clustered into modes characterized by differential glycolysis, oxidative phosphorylation, and growth rate. We also found that the simulated activities of metabolic pathways are intrinsically prognostic across cancer types, especially tumor growth rate, fatty acid biosynthesis, folate metabolism, oxidative phosphorylation, steroid metabolism, and glutathione metabolism. This work shows the prognostic power of individual patient metabolic modeling across multiple cancer types. Additionally, it shows that analyzing large-scale models of cancer metabolism with survival information provides unique insights into underlying relationships across cancer types and suggests how therapies designed for one cancer type may be repurposed for use in others. [ABSTRACT FROM AUTHOR]

Introduction: Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer and the main treatment is surgery. The extent of surgery depends on the spread of tumour and often involves thyroidectomy and neck dissection. Recurrent or metastasis tumour can be detected with raising calcitoninand there are various options of treatment. Methods: This was a retrospective study of MTC over seven years in a tertiary cancer centre which evaluated the treatment outcome and the non-surgical options available in recurrent and metastatic tumours. Results: Among the 601 thyroid cancers, 34 patients (5.3%) were MTC, of which 29 were studied. Majority were women, below 60 years, were diagnosed with fine needle aspiration cytology of thyroid nodule or nodes and had raised calcitonin value (Ctn). The value of Ctn was correlated with tumour burden rather than extent (p=0.7). Recurrence was seen in 35% and all patients with locoregional recurrence had curative surgery whereas metastatic patients were offered palliative treatment. Acceptance of palliative treatment was less due to financial burden. The five year overall survival for nonmetastatic disease was 89.4 % and for patients with metastatic disease at presentation was 54.7 %. Conclusion: The incidence of medullary thyroid carcinoma is low compared to the differentiated thyroid carcinoma. The main treatment is surgery and other treatment options are limited. [ABSTRACT FROM AUTHOR]

Introduction The observational multicenter prospective FLOWER study (NCT04965701) confirmed effectiveness and safety of osimertinib in the real-world (RW) management of untreated EGFR -mutant advanced non-small cell lung cancer (aNSCLC) patients. Methods Herein, we report updated survival data, post-progression management, cost/effectiveness and budget impact (BI) of osimertinib compared with a RW population receiving gefitinib or erlotinib. Results Overall, 189 Caucasian patients receiving first-line osimertinib were included. After a follow-up of 20.7 months, 74(39.2%) patients discontinued osimertinib, median time-to-treatment discontinuation (mTTD) was 27.9 months, overall survival 36.8 months. At progression, tissue biopsy was performed in 29 (56.9%), liquid biopsy in 15 (29.4%) and both in 7 (13.7%) cases. The most frequent resistant mechanism was MET amplification (N  = 14, 29.8%). At data cutoff, 13 (6.9%) patients were continuing osimertinib beyond progression; 52 (67.5%) received second-line treatment; no further treatments were administered in 25 (32.5%) cases. Thirty-three (63.4%) patients received chemotherapy, 12(23.1%) TKIs combination. Cost–effectiveness analysis showed a total cost per patient based on RW mTTD of 98,957.34€, 21,726.28€ and 19,637.83€ for osimertinib, erlotinib and gefitinib, respectively. The incremental cost-effectiveness ratio (ICER)/month for osimertinib was 359,806.0€/life-year-gained (LYG) and 197,789.77€/LYG compared to erlotinib and gefitinib. For osimertinib, the BI-gap between RW-TTD and theoretical-TTD was 16,501.0€ per patient. Conclusions This updated analysis confirms the effectiveness of osimertinib in RW. Although the ICER of osimertinib seems not cost-effective, additional costs for the management of disease progression to old generation TKIs were not considered in this study. The BI-gap suggests RW mTTD as a more reliable measure for expense estimation. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative 18F‐FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs). Methods: This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment 18F‐FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index‐1 (HI‐1; standard deviation [SD] divided by SUVmean) and heterogeneity index‐2 (HI‐2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed. Results: The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI‐1 were significant prognostic factors for progression‐free survival (PFS), while MTV, HI‐2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI‐1 (p < 0.001) and TNM stage (p = 0.002) were independent prognostic factors for PFS. For the overall survival analysis, TNM stage, WHO classification, SUVmax, and HI‐1 were significant prognostic factors in the univariate analysis, while TNM stage remained an independent prognostic factor in multivariate analyses (p = 0.024). The Kaplan Meier survival analyses showed worse prognoses for patients with TNM stages III and IV and HI‐1 ≥ 0.16 compared to those with stages I and II and HI‐1 < 0.16 (log‐rank p < 0.001). Conclusion: HI‐1 and TNM stage were independent prognostic factors for progression‐free survival in TETs. HI‐1 generated from baseline 18F‐FDG PET/CT might be promising to identify patients with poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Abnormal lipid levels have been associated with cancer incidence and progression. However, limited studies have investigated the relationship between apolipoprotein A-I (ApoA-I) and colorectal cancer (CRC). This study assessed the significance of ApoA-I levels in progression-free survival (PFS) and overall survival (OS) of patients with CRC. Methods: Survival curves were compared using Kaplan-Meier analysis, while the predictive values of various lipid indicators in CRC prognosis were evaluated based on receiver operating characteristic curves. The factors influencing PFS and OS in patients with CRC were analyzed using Cox proportional hazards regression models. Finally, the relationship between ApoA-I level and disease recurrence was investigated through logistic regression analysis. The optimal Apo-I level was determined through maximally selected rank statistics. Results: Using the optimal ApoA-I cutoff value (0.9 g/L), the 1,270 patients with CRCwere categorized into low (< 0.9 g/L, 275 cases) and high (=0.9 g/L, 995 cases) ApoA-I groups. Compared with other lipid indicators, ApoA-I demonstrated superior predictive accuracy. The high ApoA-I group exhibited significantly higher survival rates than the low ApoA-I group (PFS, 64.8% vs. 45.2%, P < 0.001; OS, 66.1% vs. 48.6%, P < 0.001). Each one-standard-deviation increase in ApoA-I level was related to a 12.0% decrease in PFS risk (hazard ratio [HR] 0.880; 95% confidence interval [CI], 0.801-0.968; P = 0.009) and an 11.2% decrease in OS risk (HR 0.888; 95%CI, 0.806-0.978; P = 0.015). Logistic regression analysis revealed that patients with low ApoA-I had a 32.5% increased risk of disease recurrence (odds ratio [OR] 0.675; 95%CI, 0.481-0.946; P = 0.0225) compared with those with high ApoA-I. PFS/OS nomograms based on ApoA-I demonstrated excellent prognostic prediction accuracy. Conclusions: Serum ApoA-I level may be a valuable and non-invasive tool for predicting PFS and OS in patients with CRC. [ABSTRACT FROM AUTHOR]

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

Objectives: The aim of this meta-analysis is to evaluate the potential benefits of postoperative radiotherapy (PORT) in patients with pN1 oral cavity squamous cell carcinoma. Methods: A literature search through major databases was conducted until January 2023. The adjusted hazard ratio (aHR) or risk ratio (RR) with 95% confidence intervals (CIs) of different survival outcomes were extracted and pooled. Results: Ten studies published between 2005 and 2022, with a pooled patient population of 2888, were included in this meta-analysis. Due to differences in study design and reported outcomes, the studies were categorized into distinct groups. In pN1 patients without extranodal extension (ENE), PORT was associated with a significant improvement in overall survival (OS) (aHR 0.76, 95% CI: 0.61-0.94). In pN1 patients without ENE and positive margins, PORT improved OS (aHR 0.71, 95% CI: 0.56-0.89) and was associated with a lower regional recurrence rate (RR 0.35, 95% CI: 0.15-0.83). However, in pN1 patients without ENE, positive margins, perineural invasion, and lymphovascular invasion, there were no significant differences observed between the PORT and observation groups in either 5-year OS (RR 0.48, 95% CI: 0.07-3.41) or 5-year disease-free survival (RR 0.37, 95% CI: 0.07-2.06). Conclusions: The current study demonstrated that PORT has the potential to improve OS in pN1 disease. However, the decision of whether to administer PORT still hinges on diverse clinical scenarios, and additional research is necessary to furnish a more conclusive resolution. [ABSTRACT FROM AUTHOR]

This study explores the predictive and monitoring capabilities of clinical and multiparametric MR parameters in assessing capecitabine and temozolomide (CAPTEM) therapy response in patients with neuroendocrine tumors (NET). This retrospective study (n = 44) assessed CAPTEM therapy response in neuroendocrine liver metastases (NELM) patients. Among 33 monitored patients, as a subgroup of the overall study cohort, pretherapeutic and follow-up MRI data (size, apparent diffusion coefficient [ADC] values, and signal intensities), along with clinical parameters (chromogranin A [CgA] and Ki-67%), were analyzed. Progression-free survival (PFS) served as the reference. Responders were defined as those with PFS ≥ 6 months. Most patients were male (75%) and had G2 tumors (76%) with a pancreatic origin (84%). Median PFS was 5.7 months; Overall Survival (OS) was 25 months. Non-responders (NR) had higher Ki-67 in primary tumors (16.5 vs. 10%, p = 0.01) and increased hepatic burden (20% vs. 5%, p = 0.007). NR showed elevated CgA post-treatment, while responders (R) exhibited a mild decrease. ADC changes differed significantly between groups, with NR having decreased ADCmin (−23%) and liver-adjusted ADCmean/ADCmean liver (−16%), compared to R's increases of ADCmin (50%) and ADCmean/ADCmean liver (30%). Receiver operating characteristic (ROC) analysis identified the highest area under the curve (AUC) (0.76) for a single parameter for ∆ ADC mean/liver ADCmean, with a cut-off of < 6.9 (76% sensitivity, 75% specificity). Combining ∆ Size NELM and ∆ ADCmin achieved the best balance (88% sensitivity, 60% specificity) outperforming ∆ Size NELM alone (69% sensitivity, 65% specificity). Kaplan-Meier analysis indicated significantly longer PFS for ∆ ADCmean/ADCmean liver < 6.9 (p = 0.024) and ∆ Size NELM > 0% + ∆ ADCmin < −2.9% (p = 0.021). Survival analysis emphasizes the need for adapted response criteria, involving combined evaluation of CgA, ADC values, and tumor size for monitoring CAPTEM response in hepatic metastasized NETs. [ABSTRACT FROM AUTHOR]

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

Simple Summary: Metastatic triple-negative breast cancer is an aggressive cancer with an average survival of 8 to 13 months. However, survival varies significantly among patients. We studied a large group of women in the National Cancer Database to better understand these survival differences. We found that the key factors influencing survival were comorbidity score (overall health status), histology (cancer subtype), number of metastatic sites (extent of cancer spread), and whether or not they received chemotherapy or immunotherapy. Our study's findings can help better predict survival based on an individual's specific factors and guide treatment strategies. Background: Metastatic triple-negative breast cancer (TNBC) is aggressive with poor median overall survival (OS) ranging from 8 to 13 months. There exists considerable heterogeneity in survival at the individual patient level. To better understand the survival heterogeneity and improve risk stratification, our study aims to identify the factors influencing survival, utilizing a large patient sample from the National Cancer Database (NCDB). Methods: Women diagnosed with metastatic TNBC from 2010 to 2020 in the NCDB were included. Demographic, clinicopathological, and treatment data and overall survival (OS) outcomes were collected. Kaplan–Meier curves were used to estimate OS. The log-rank test was used to identify OS differences between groups for each variable in the univariate analysis. For the multivariate analysis, the Cox proportional hazard model with backward elimination was used to identify factors affecting OS. Adjusted hazard ratios and 95% confidence intervals are presented. Results: In this sample, 2273 women had a median overall survival of 13.6 months. Factors associated with statistically significantly worse OS included older age, higher comorbidity scores, specific histologies, higher number of metastatic sites, presence of liver or other site metastases in those with only one metastatic site (excluding brain metastases), presence of cranial and extra-cranial metastases, lack of chemotherapy, lack of immunotherapy, lack of surgery to distant sites, lack of radiation to distant sites, and receipt of palliative treatment to alleviate symptoms. In the multivariate analysis, comorbidity score, histology, number of metastatic sites, immunotherapy, and chemotherapy had a statistically significant effect on OS. Conclusions: Through NCDB analysis, we have identified prognostic factors for metastatic TNBC. These findings will help individualize prognostication at diagnosis, optimize treatment strategies, and facilitate patient stratification in future clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Little is known regarding the significance of tumor burden in the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Patients were stratified into high tumor burden (HTB) and low tumor burden (LTB) groups according to their tumor burden score. Our study showed tumor burden was significantly correlated with survival in R/M HNSCC patients, independent of PD-L1 status. HTB patients receiving EPF had better survival than those receiving PPF, regardless of PD-L1 expression. For LTB PD-L1 positive patients, there was a longer survival on PPF than EPF. For LTB PD-L1 negative patients, survival was similar between PPF and EPF. Hence, PD-L1 and TBS should be considered by the multi-disciplinary team for the treatment of R/M HNSCC. Background: The significance of tumor burden for survival is unknown for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The purpose of our study was to evaluate the prognostic impact of programmed death ligand-1 (PD-L1) and tumor burden score (TBS) in patients with R/M HNSCC. Patients and Methods: R/M HNSCC patients who were treated with cisplatin, 5-fluorouracil plus cetuximab (EPF) or pembrolizumab (PPF) as first-line treatment were included in our study. PD-L1 and TBS were estimated and correlated with treatment responses. Kaplan–Meier curves were plotted for outcomes estimation. Results: A total of 252 R/M HNSCC patients were included, with 126 high tumor burden (HTB) and 126 low tumor burden (LTB) patients. Median progression-free survival (PFS) was 7.1 months in LTB and 3.9 months in HTB (p < 0.001) and median overall survival (OS) was 14.2 months in LTB and 9.2 months in HTB (p = 0.001). Patients with LTB had better PFS and OS than those with HTB independent of PD-L1 status. Subgroup analysis showed HTB patients treated with EPF had better survival than those treated with PPF, regardless of PD-L1 expression. For LTB PD-L1 positive patients, there was a longer survival with PPF than EPF, while for LTB PD-L1 negative patients, survival was similar between PPF and EPF. Multivariate analysis exhibited that tumor burden was significantly correlated with OS. Conclusions: Tumor burden is significantly correlated with survival in patients with R/M HNSCC. PD-L1 and TBS should be taken into consideration to determine first-line treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, with almost half of all patients diagnosed with non-metastatic disease (stage IA–IIIC). The treatment options for patients with NSCLC are evolving rapidly, and survival outcomes have improved since the introduction of immunotherapies and targeted treatments in the non-metastatic setting. In this study, we explored treatment patterns and outcomes for patients with non-metastatic NSCLC in Sweden prior to the availability of these treatments. Patient outcomes were comparable with those reported in other real-world studies; however, the prognosis for patients with NSCLC, particularly at higher disease stages, remained poor. These results provide a baseline upon which to evaluate the effectiveness of immunotherapies and targeted treatments as they are introduced into routine clinical practice, including for patients in the non-metastatic setting. Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, with ~40–50% of patients diagnosed with non-metastatic disease (stages IA–IIIC). The treatment landscape is evolving rapidly as immunotherapies and targeted therapy are introduced in the non-metastatic setting, creating a need to assess patient outcomes prior to their introduction. This real-world study using Swedish National Lung Cancer Registry data examined outcomes (overall survival (OS) and time to next treatment or death (TTNTD)) and treatment patterns for adults diagnosed with non-metastatic NSCLC. Baseline characteristics and OS from diagnosis were described for all patients; OS, treatment patterns, and TTNTD from treatment start were described for the treatment subgroup (patients diagnosed from 2014 onwards), stratified by disease stage and initial treatment. OS and TTNTD were described using the Kaplan–Meier estimator. The overall population (2008–2019) included 17,433 patients; the treatment subgroup included 5147 patients. Median OS (interquartile range) overall ranged from 83.3 (31.6–165.3) months (stage I patients) to 10.4 (4.3–24.2) months (stage IIIB patients). Among the treatment subgroup, median OS and TTNTD were longest among patients receiving surgery versus other anticancer treatments. These findings provide a baseline upon which to evaluate the epidemiology of non-metastatic NSCLC as newer treatments are introduced. [ABSTRACT FROM AUTHOR]

Objective. Programmed cell death-1 (PD-1) inhibitors have shown potency for neoadjuvant therapy in several cancers, while their administration combined with concurrent chemoradiotherapy (CCRT) as a neoadjuvant therapy for locally advanced esophageal squamous-cell carcinoma (ESCC) is seldom reported. The current study aimed to investigate the pathological response, survival, and safety of neoadjuvant PD-1 inhibitor plus CCRT in locally advanced ESCC patients. Methods. Twenty-five locally advanced ESCC patients who underwent PD-1 inhibitor plus CCRT neoadjuvant therapy were retrospectively reviewed. Data regarding radiological response, pathological response, disease-free survival (DFS), overall survival (OS), and adverse events were retrieved. Results. Two (8.0%), 14 (56.0%), 9 (36.0%), and 0 (0.0%) patients had a clinical response of complete response, partial response, stable disease, and progressive disease after neoadjuvant therapy by radiological evaluations, respectively. Notably, 25 (100.0%) patients had successful tumor resections, 24 (96.0%) patients realized R0 resection, and 13 (52.0%) patients achieved pathological complete response (pCR) by pathological evaluations. Regarding survival profiles, the 1-year and 2-year accumulating DFS rates were 90.0% and 74.6%, respectively; then, the 1-year and 2-year accumulating OS rates were 95.5% and 90.4%, respectively. The top prevalent adverse events were fatigue (48.0%), nausea and vomiting (40.0%), leukopenia (36.0%), neutropenia (36.0%), and peripheral neuropathy (36.0%). In addition, grades 3-4 adverse events included peripheral neuropathy (12.0%), nausea and vomiting (4.0%), leukopenia (4.0%), neutropenia (4.0%), anemia (4.0%), and pruritus (4.0%). Conclusion. Neoadjuvant PD-1 inhibitor plus CCRT shows a good efficacy and acceptable tolerance for locally advanced ESCC treatment, but further large-scale study validation is needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths worldwide, with liver resection being the most effective for curative intent. The hepatic venous pressure gradient (HVPG), transient elastography-liver stiffness measurement (TE-LSM), and TAC score are intricately connected with the postoperative evolution of cirrhosis. The primary objective of our study is to evaluate the predictive value of key parameters for surgical patients. The proposed predictors can better presume treatment outcomes in HCC and potentially allow an improvement in therapeutic strategy. Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and the third contributor to malignancy-related deaths worldwide. The hepatic venous pressure gradient (HVPG), transient elastography-liver stiffness measurement (TE-LSM), and the association between TBS (tumor burden score), alpha-fetoprotein levels, and the Child–Pugh classification (TAC score) can serve as valuable prognostic indicators for these patients. Therefore, the main objective of our research was to analyze the prognostic value of the HVPG, TE-LSM, TBS, and TAC scores. An observational and survival study was conducted on 144 subjects. Our findings indicated that HVPG greater than 10 mmHg, AFP surpassing 400 ng/mL, an advanced C–P class, and low TAC score are independent predictors of overall survival. During the multivariate analysis, AFP serum levels and C–P class proved statistically significant. The present study revealed significant differences in overall survival between the two groups divided upon HVPG values and settled by the cutoff of 10 mmHg (p = 0.02). Moreover, by dividing the cohort into three groups based on the TAC score (very low, low, and moderate), statistically significant differences in overall survival were observed across the groups (p = 0.004). [ABSTRACT FROM AUTHOR]

Simple Summary: Currently, hepatocellular carcinoma (HCC) is one of the most prevalent oncological diagnoses worldwide. Despite intensive research into its pathogenesis and clinical course, numerous issues remain unresolved. In the presented meta-analysis and systematic review, we investigate the potential of blood platelet levels in patients with HCC for prognostic assessment. Blood platelets may play a significant role as an easily measurable laboratory parameter in assessing the prognosis of patients with HCC. Background: Platelets (PLT) have a role in the pathogenesis, progression, and prognosis of hepatocellular carcinoma (HCC) and could represent a readily measurable laboratory parameter to enhance the comprehensive evaluation of HCC patients. Methods: The PubMed, Web of Science, and Scopus databases were searched with a focus on survival as well as patient and tumor-specific characteristics in correlation to reported PLT counts. Survival outcomes were analyzed with both common-effect and random-effects models. The hazard ratio (HR) and its 95% confidence interval (CI) from analyzed trials were incorporated. Studies that did not provide survival data but focused on platelet count correlation with HCC characteristics were reviewed. Results: In total, 26 studies, including a total of 9403 patients, met our criteria. The results showed that thrombocytopenia in HCC patients was associated with poor overall survival (common-effect HR = 1.15, 95% CI: 1.06–1.25; random-effect HR = 1.30, 95% CI: 1.05–1.63). Moreover, three studies reveal significant correlations between PLT indices and tumor characteristics such as size, foci number, and etiology of HCC development. Conclusion: Our meta-analysis confirmed that PLT count could act as a prognostic marker in HCC, especially with a PLT count cut off <100 × 103/mm3. Further prospective studies focusing on the role of PLT in clearly defined subgroups are necessary. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to pinpoint immune-related genes that show heightened activity in cancerous tissue and explore their correlation with cell infiltration in the tumor microenvironment using bioinformatics analysis. By examining gene expression from both stomach cancer and adjacent healthy tissues, we aimed to uncover their significance in cancer development and their impact on the body's immune response. We identified several genes, including FN1, COL1A2, THBS2, COL3A1, COL5A1, and BGN, which appear to be associated with poorer outcomes for stomach cancer patients. These genes also demonstrate connections to specific immune cells within cancerous tissue. Understanding the role of these genes in the immune response to cancer could facilitate the development of novel treatments and enhance prognostic capabilities for individuals with stomach cancer. Objective: Gastric carcinoma (GC) is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related deaths globally. The tumor microenvironment plays a significant role in the pathogenesis, prognosis, and response to immunotherapy. However, the immune-related molecular mechanisms underlying GC remain elusive. Bioinformatics analysis of the gene expression of GC and paracancerous healthy tissues from the same patient was performed to identify the key genes and signaling pathways, as well as their correlation to the infiltration of the tumor microenvironment (TME) by various immune cells related to GC development. Methods: We employed GSE19826, a gene expression profile from the Gene Expression Omnibus (GEO), for our analysis. Functional enrichment analysis of Differentially Expressed Genes (DEGs) was conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database. Results: Cytoscape software facilitated the identification of nine hub DEGs, namely, FN1, COL1A1, COL1A2, THBS2, COL3A1, COL5A1, APOE, SPP1, and BGN. Various network analysis algorithms were applied to determine their high connectivity. Among these hub genes, FN1, COL1A2, THBS2, COL3A1, COL5A1, and BGN were found to be associated with a poor prognosis for GC patients. Subsequent analysis using the TIMER database revealed the infiltration status of the TME concerning the overexpression of these six genes. Specifically, the abovementioned genes demonstrated direct correlations with cancer-associated fibroblasts, M1 and M2 macrophages, myeloid-derived suppressor cells, and activated dendritic cells. Conclusion: Our findings suggest that the identified hub genes, particularly BGN, FN1, COL1A2, THBS2, COL3A1, and COL5A1, play crucial roles in GC prognosis and TME cell infiltration. This comprehensive analysis enhances our understanding of the molecular mechanisms underlying GC development and may contribute to the identification of potential therapeutic targets and prognostic markers for GC patients. [ABSTRACT FROM AUTHOR]

Background Primary therapy of localized myxofibrosarcoma (MFS) remains controversial. Primary resection is complicated by a high rate of local recurrence, and the refractoriness to non-surgical treatment results in a higher risk of metastasis. The aim of the present study was to contribute the findings of a single sarcoma-specialized center and encourage investigating new treatment options. Patients and Methods We analyzed 134 patients treated with localized MFS in our center regarding prognostic factors defining overall survival, local recurrence, and metastasis. We focused on multimodal treatment of localized MFS: surgery, radiation, chemotherapy, hyperthermia, and isolated limb perfusion. Results The 5-year OS was 74.9%. From a total of 134 patients: 74 (55.2%) stayed disease free, 48 (35.8%) had a local recurrence (LR), and 23 (17.2%) developed a distant metastasis (DM). The 5-year LR-free survival (LRFS) and DM-free survival (DMFS) were 66.1% and 80.8%, respectively. Older age, tumor size (cT) cT ≥ 2, non-extremity localization, and distant metastasis were adverse predictive factors for OS. Performing an incision biopsy, surgery in a sarcoma-center, wide local excision or compartment-oriented excision, negative margins, and radiotherapy were positive predictive factors for LR. Tumor size cT ≥ 3 was a negative predictive factor for DM. Grading was a negative predictive factor for LR (G ≥ 2) and for DM (G3) in the multivariable analysis. Conclusion Adjuvant radiation had a positive impact on LRFS in all localized tumor stages, even in cT1 tumors. Chemotherapy did not have a significant impact on DMFS, regardless of tumor stage. Our findings indicate that myxofibrosarcoma may be a chemotherapy-resistant entity and a much closer monitoring is required, in case of neoadjuvant treatment. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to explore the relationships between single-nucleotide polymorphisms (SNPs) of crucial molecules in the cGAS-STING signalling pathway and the susceptibility to, induction chemotherapy response of, and prognosis of acute myeloid leukaemia (AML) in Chinese patients. Methods: Thirteen SNPs of crucial molecules in the cGAS-STING signalling pathway were genotyped in 262 AML patients using the Sequenom MassARRAY system. The associations of SNPs with susceptibility, and induction chemotherapy response were analysed using the chi-square test or Fisher's exact test and univariate binary logistic regression, the connection of SNPs with prognosis of AML was analysed using the log-rank test, and Kaplan–Meier curves were applied for survival estimation. Results: In our study, gene polymorphisms of cGAS-STING signalling pathway molecules could be vitally associated with AML. In the recessive model, the cGAS rs311678 gene polymorphism could be closely related to AML susceptibility (CC vs. TT + TC, odds ratio (OR) = 0.480, 95% confidence interval (CI) = 0.260–0.889, p = 0.020). Moreover, IKKA rs3808917 might be associated with the WBC count, cGAS rs311678 could be associated with the bone marrow (BM) blast percentage, and NF-κB rs1056890 under codominant and recessive models could be connected with the HGB level. Patients who were STING rs7380272 TT/CT carriers was likely to have higher insensitivity to induction chemotherapy than CC carriers (TT + CT vs. CC, OR = 2.917, 95% CI = 1.073–7.929, p = 0.036). Survival analysis indicated that the IKKB rs3747811 TT genotype might be associated with decreased overall survival (OS) (p < 0.05). Conclusions: SNPs of molecules in the cGAS-STING signalling pathway could be significantly associated with AML. The cGAS rs311678 gene polymorphism could be associated with AML susceptibility, the STING rs7380272 variant might be related to induction chemotherapy response, and IKKB rs3747811 tended to be associated with AML overall survival. Moreover, IKKA rs3808917 could be associated with the WBC count, cGAS rs311678 could be associated with the BM blast percentage, and NF-κB rs1056890 might be related to the HGB level. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammation and glucose metabolism have been closely related to the survival of cancer patients. Therefore, we aimed to evaluate whether preoperative glucose-to-lymphocyte ratio (GLR) can be used to predict the survival of cancer patients. Methods: We retrospectively examined 2172 cancer patients who underwent surgery from January 1, 2014, to December 31, 2016. There were 240 patients with non-small cell lung cancer (NSCLC), 378 patients with colorectal cancer (CRC), 221 patients with breast cancer (BC), 335 patients with gastric cancer (GC), 270 patients with liver cancer, 233 patients with esophageal cancer (EC), 295 patients with renal cancer, and 200 patients with melanoma. The formula for preoperative GLR calculation was as follows: GLR=glucose/lymphocyte count. The overall survival (OS) was estimated using the Kaplan-Meier method. The predictive factors for OS were determined using multivariate analysis. Results: The Kaplan-Meier analysis showed that the median survival time in the high-GLR group was much shorter than that of those in the low-GLR group for different cancers. Cox multivariate regression analysis reveals that preoperative GLR was an independent factor for predicting overall survival in different tumor types. Conclusion: Elevated preoperative GLR was remarkably associated with a poorer prognosis in patients with NSCLC, CRC, breast cancer, gastric cancer, kidney cancer, liver cancer, esophageal cancer, and melanoma. Preoperative GLR promises to be an essential predictor of survival for cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: B-cell acute lymphoblastic leukemia is genetically diverse, with one of the most commonly altered genes being PAX5. Recently, alterations in PAX5 have been identified not merely as secondary events, but also as the oncogenic drivers, with newly defined genetic subtypes like PAX5alt and PAX5 P80R. Studying a consecutive cohort of 99 B-ALL patients, we found PAX5 alterations in over a third of patients, mostly involving copy number variations. Seven of our patients exhibited the PAX5alt genetic profile and one carried the P80R variant, and these patients showed intermediate outcomes. We also discovered that patients within the hyperdiploid group that carried extra copies of PAX5 did not respond as well to the treatment. Overall, our study highlights widespread PAX5 alterations affecting treatment response, particularly in specific genetic subtypes, underlining the need to identify these alterations for improved treatment strategies. In this study, we aimed to identify patients within our B-ALL cohort with altered PAX5. Our objective was to use a comprehensive analysis approach to characterize the types of genetic changes, determine their origin (somatic/germline), and analyze the clinical outcomes associated with them. A consecutive cohort of 99 patients with B-ALL treated at the Children's Hospital of the UMC Ljubljana according to the ALL IC-BFM 2009 protocol was included in our study. We used RNA sequencing data for gene expression analysis, fusion gene detection and single nucleotide variant identification, multiplex-ligation dependent probe amplification for copy number variation assessment, and Sanger sequencing for germline variant detection. PAX5 was impacted in 33.3% of our patients, with the genetic alterations ranging from CNVs and rearrangements to SNVs. The most common were CNVs, which were found in more than a third of patients, followed by point mutations in 5.2%, and gene rearrangements in 4.1%. We identified eight patients with a PAX5-associated genetic subtype that were previously classified as "B-other", and they showed intermediate outcomes. We showed higher minimal residual disease values at the end of induction and poorer event-free survival in hyperdiploid cases carrying duplications in PAX5 compared to other hyperdiploid cases. We also report an interesting case of a patient with PAX5::FKBP15 and a pathogenic variant in PTPN11 who underwent an early relapse with a monocytic switch. In conclusion, this study provides valuable insights into the presence, frequency, and prognostic significance of diverse PAX5 alterations in B-ALL patients, highlighting the complexity of genetic factors and their impact on patient outcomes. [ABSTRACT FROM AUTHOR]

Background. Ewing sarcoma (EwS) is a rare and highly malignant bone tumor primarily affecting children, adolescents, and young adults. The pelvis, trunk, and lower extremities are the most common sites, while EwS of the sacrum as a primary site is very rare, and only few studies focusing on this location are published. Due to the anatomical condition, local treatment is challenging in sacral malignancies. We analyzed factors that might influence the outcome of patients suffering from sacral EwS. Methods. We retrospectively analyzed data of the GPOH EURO-E.W.I.N.G 99 trial and the EWING 2008 trial, with a cohort of 124 patients with localized or metastatic sacral EwS. The study endpoints were overall survival (OS) and event-free survival (EFS). OS and EFS were calculated using the Kaplan–Meier method, and univariate comparisons were estimated using the log-rank test. Hazard ratios (HRs) with respective 95% confidence intervals (CIs) were estimated in a multivariable Cox regression model. Results. The presence of metastases (3y-EFS: 0.33 vs. 0.68; P < 0.001 ; HR = 3.4, 95% CI 1.7 to 6.6; 3y-OS: 0.48 vs. 0.85; P < 0.001 ; HR = 4.23, 95% CI 1.8 to 9.7), large tumor volume (≥200 ml) (3y-EFS: 0.36 vs. 0.69; P = 0.02 ; HR = 2.1, 95% CI 1.1 to 4.0; 3y-OS: 0.42 vs. 0.73; P = 0.04 ; HR = 2.1, 95% CI 1.03 to 4.5), and age ≥18 years (3y-EFS: 0.41 vs. 0.60; P = 0.02 ; HR = 2.6, 95% CI 1.3 to 5.2; 3y-OS: 0.294 vs. 0.59; P = 0.01 ; HR = 2.92, 95% CI 1.29 to 6.6) were revealed as adverse prognostic factors. Conclusion. Young age seems to positively influence patients' survival, especially in patients with primary metastatic disease. In this context, our results support other studies, stating that older age has a negative impact on survival. Tumor volume, metastases, and the type of local therapy modality have an impact on the outcome of sacral EwS. Level of evidence: Level 2. This trial is registered with NCT00020566 and NCT00987636. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to investigate the effect of spread through air spaces (STAS) on the postoperative prognosis of patients with multiple primary lung cancers staged from IA to IB based on tumor size. Methods: Clinicopathological and follow-up data of 122 patients with multiple primary lung cancers diagnosed at stages IA-IB and surgically treated at the Department of Thoracic Surgery, Shenzhen people's Hospital from January 2019 to December 2021 were retrospectively analyzed. The study involved 42 males and 80 females. STAS status was used to divide them into two groups (87 cases in STAS (-) and 35 cases in STAS (+)). A logistic regression analysis, univariate and multivariate Cox regression analysis, and Kaplan-Meier curves (K-M) were used to determine how STAS affected recurrence-free survival (RFS) in patients. Results: STAS (+) had a significantly higher recurrence rate than STAS (-). STAS was predicted by smoking history (P = 0.044), main tumor diameter (P = 0.02), and solid nodules on chest CT (P = 0.02). STAS incidence was not significantly different between lobectomy and sublobar resection groups (P = 0.17). Solid nodules on CT, tumor diameter, vascular invasion, pleural invasion, and STAS were significant predictors of recurrence in the univariate Cox regression analysis. Tumor diameter, pleural invasion and STAS were significant prognostic factors for recurrence in the multivariate Cox regression analysis. Furthermore, STAS (+) group was at greater risk of recurrence than STAS (-) group (34% vs. 0%, P < 0.05)。. Conclusion: Stage IA-IB multiple primary lung cancer patients with STAS (+) had a higher recurrence rate and a shorter overall survival rate. [ABSTRACT FROM AUTHOR]

Simple Summary: Local ablation therapies are important treatment options for hepatocellular carcinoma (HCC). Some HCC nodules were classified as HCC in high-risk locations based on ultrasound (US) if they were adjacent to large vessels or extrahepatic organs or if they were poorly visible on US. Various techniques have been used to perform these therapies efficiently and safely. However, few reports have discussed the usefulness of body position change (BPC). The aim of our study was to assess the usefulness of BPC during radiofrequency ablation therapies in patients with HCC. We confirmed the high technical success rates in patients with BPC, and no differences in the procedure time, local tumor progression rates, intrahepatic distant recurrence rates, and overall survival between the groups with and without BPC in the high-risk location group. Performing BPC during local ablation therapies in patients with HCC in high-risk locations may enable safe and accurate treatment. Local ablation therapies are important treatment options for early-stage hepatocellular carcinoma (HCC). Various techniques have been used to perform these therapies efficiently and safely. However, few reports have discussed the usefulness of body position change (BPC). This study aimed to investigate the usefulness of BPC during local ablation therapies in patients with HCC. We evaluated 283 HCC nodules that underwent local ablation therapy. These nodules were categorized into high- or low-risk locations on the basis of their proximity to large vessels, adjacent extrahepatic organs, or poor visibility under ultrasound (US) guidance. The technical success rates, procedure time, and prognosis were evaluated. In this study, 176 (62%) nodules were classified in the high-risk location group. The high-risk location group was treated with techniques such as BPC, artificial pleural fluid, artificial ascites, fusion imaging, and contrast-enhanced US more frequently than the low-risk location group. The technical success rates were 96% and 95% for the high- and low-risk location groups, respectively. Within the high-risk location group, those without BPC had a lower success rate than those with BPC (91% vs. 99%, p = 0.015). Notably, BPC emerged as the sole contributing factor to the technical success rate in the high-risk location group (OR = 10, 95% CI 1.2–86, p = 0.034). In contrast, no differences were found in the procedure time, local tumor progression rates, intrahepatic distant recurrence rates, and overall survival between the groups with and without BPC in the high-risk location group. In conclusion, BPC during local ablation therapy in patients with HCC in high-risk locations was safe and efficient. The body position should be adjusted for HCC in high-risk locations to maintain good US visibility and ensure a safe puncture route in patients undergoing local ablation therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Primary cutaneous B-cell lymphomas account for approximately 25% of all cutaneous lymphomas and 2% of all non-Hodgkin's lymphomas. Three main entities are recognized: primary cutaneous marginal zone lymphoma, primary cutaneous follicle centre lymphoma, and primary cutaneous diffuse large B-cell lymphoma, leg type. In this article, the Spanish Lymphoma Oncology Group (GOTEL) presents a series of 103 primary cutaneous B-cell lymphomas. Primary cutaneous B-cell lymphomas (PCBCLs) are B-cell lymphomas that can occur in the skin without evidence of extracutaneous involvement. The 2005 WHO/EORTC classification of cutaneous lymphomas and its 2018 update have distinguished three main categories based on clinicopathological, immunohistochemical, and genetic characteristics: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT). PCMZL and PCFCL are clinically indolent, while PCDLBCL-LT is an aggressive lymphoma. Due to its low incidence and lack of prospective studies, it is difficult to establish a standard treatment for each subgroup. The objective of our study was to describe the clinical and pathological characteristics of 103 patients with cutaneous B-cell lymphoma from 12 centres belonging to the Spanish Lymphoma Oncology Group. The median age was 53 years (40–65). According to skin extension, 62% had single-site lymphoma, 17% had regional lymphoma, and 20% had multifocal lymphoma. Histology: 66% had PCMZL, 26% had PCFCL, and 8% had PCDLBCL-LT. Twenty-three percent of the patients were treated exclusively with surgery, 26% with radiotherapy only, 21% with surgery plus radiotherapy, 10% with polychemotherapy, and 5% with rituximab monotherapy. Overall, 96% of patients achieved a complete response, and 44% subsequently relapsed, most of them relapsing either locally or regionally. The 10-year OS was 94.5% for the entire cohort, 98% for the PCMZL cohort, 95% for the PCFCL cohort, and 85.7% for the PCDLBCL-LT cohort. Our data are comparable to those of other published series, except for the high frequency of PCMZL. The expected heterogeneity in therapeutic management has been observed. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors are standard treatment for patients with metastatic melanoma, and treatment response is most optimally evaluated with FDG-PET/CT. Pseudoprogression describes the difficulty of distinguishing between real cancer growth and growth occurring due to active infiltrating immune cells that mistakenly look like tumor growth on scans. The aim of our study was to investigate whether dual-time point (DTP) FDG-PET/CT scan and modified response criteria (PERCIMT) could be helpful in detecting pseudoprogression. Our findings suggest limited efficacy of DTP FDG-PET/CT whereas PERCIMT criteria could be included in the clinical decision making ensuring correct treatment choices. The activity of immune checkpoint inhibitors (ICIs) in patients with metastatic melanoma is often monitored using fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scans. However, distinguishing disease progression (PD) from pseudoprogression (PsPD), where increased FDG uptake might reflect immune cell activity rather than tumor growth, remains a challenge. This prospective study compared the efficacy of dual-time point (DTP) FDG-PET/CT with modified response criteria (PERCIMT) in differentiating PsPD from PD. From July 2017–January 2021, 41 patients suspected to have PsPD on an evaluation scan were prospectively included (29 evaluable). A subsequent DTP FDG-PET/CT scan was conducted within 14 days, followed by a confirmatory FDG-PET/CT scan. Additionally, PERCIMT were applied. DTP FDG-PET/CT identified 24% with PsPD and 76% with PD. Applying PERCIMT criteria, 69% showed PsPD, while 31% had PD. On follow-up, 10 patients (34%) demonstrated confirmed PsPD, while 19 (66%) exhibited PD. The sensitivity and specificity of DTP FDG-PET/CT were 20% and 74%, respectively, and for PERCIMT this was 80% and 37%, respectively. Our findings suggest limited efficacy of DTP FDG-PET/CT in distinguishing PsPD from PD in ICI-treated patients with metastatic melanoma. The use of PERCIMT could complement clinical assessment and be incorporated in multidisciplinary team conferences for enhanced decision-making. [ABSTRACT FROM AUTHOR]

Simple Summary: Adjuvant chemotherapy (AC) with S1 is beneficial for pancreatic cancer, but the completion rate of S1 remains at 70%. Additionally, there are no useful indicators for achieving completion of S1. Therefore, we have assumed that studying the C-reactive protein-to-albumin ratio as an indicator based on nutritional status may be useful in predicting this. When this indicator proves effective, we believe that more cases can complete the treatment by improving nutrition or adjusting the dosage before starting AC. Adjuvant chemotherapy (AC) with S-1 after radical surgery for resectable pancreatic cancer (PC) has shown a significant survival advantage over surgery alone. Consequently, ensuring that patients receive a consistent, uninterrupted S-1 regimen is of paramount importance. This study aimed to investigate whether the C-reactive protein-to-albumin ratio (CAR) could predict S-1 AC completion in PC patients without dropout due to adverse events (AEs). We retrospectively enrolled 95 patients who underwent radical pancreatectomy and S-1 AC for PC between January 2010 and December 2022. A statistical analysis was conducted to explore the correlation of predictive markers with S-1 completion, defined as continuous oral administration for 6 months. Among the 95 enrolled patients, 66 (69.5%) completed S-1, and 29 (30.5%) failed. Receiver operating characteristic curve analysis revealed 0.05 as the optimal CAR threshold to predict S-1 completion. Univariate and multivariate analyses further validated that a CAR ≥ 0.05 was independently correlated with S-1 completion (p < 0.001 and p = 0.006, respectively). Furthermore, a significant association was established between a higher CAR at initiation of oral administration and acceptable recurrence-free and overall survival (p = 0.003 and p < 0.001, respectively). CAR ≥ 0.05 serves as a predictive marker for difficulty in completing S-1 treatment as AC for PC due to AEs. [ABSTRACT FROM AUTHOR]

Simple Summary: A 10-year experience in cancer therapy using concomitant treatment of immunotherapy and percutaneous thermal ablation is shared in this article. Based on a retrospective cohort of 78 patients, the feasibility, safety and efficacy of such combined treatments were assessed. Most patients received immune checkpoint blocker monotherapy combined with radiofrequency or cryotherapy ablation. The feasibility and safety profile were found to be excellent, with complications equivalent to those reported when each treatment was performed separately. Overall, thermal ablation outcomes were found to be similar to standards for patients not on immunotherapy. Purpose: We report a 10-year experience in cancer therapy with concomitant treatment of percutaneous thermal ablation (PTA) and immune checkpoint blockers (ICBs). Material and methods: This retrospective cohort study included all patients at a single tertiary cancer center who had received ICBs at most 90 days before, or 30 days after, PTA. Feasibility and safety were assessed as the primary outcomes. The procedure-related complications and immune-related adverse events (irAEs) were categorized according to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE). Efficacy was evaluated based on overall survival (OS), progression-free survival (PFS), and local progression-free survival (LPFS) according to the indication, ablation modality, neoplasm histology, and ICB type. Results: Between 2010 and 2021, 78 patients (57% male; median age: 61 years) were included. The PTA modality was predominantly cryoablation (CA) (61%), followed by radiofrequency ablation (RFA) (31%). PTA indications were the treatment of oligo-persistence (29%), oligo-progression (14%), and palliation of symptomatic lesions or prevention of skeletal-related events (SREs) (56%). Most patients received anti-PD1 ICB monotherapy with pembrolizumab (n = 35) or nivolumab (n = 24). The feasibility was excellent, with all combined treatment performed and completed as planned. Ten patients (13%) experienced procedure-related complications (90% grade 1–2), and 34 patients (44%) experienced an irAE (86% grade 1–2). The only factor statistically associated with better OS and PFS was the ablation indication, favoring oligo-persistence (p = 0.02). Tumor response was suggestive of an abscopal effect in four patients (5%). Conclusions: The concomitant treatment of PTA and ICBs within 2–4 weeks is feasible and safe for both palliative and local control indications. Overall, PTA outcomes were found to be similar to standards for patients not on ICB therapy. While a consistently reproducible abscopal effect remains elusive, the safety profile of concomitant therapy provides the framework for continued assessment as ICB therapies evolve. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the outcomes of elderly patients with limited‐stage small cell lung cancer (LS‐SCLC), which may be linked to the timing of thoracic radiotherapy (TRT) following chemotherapy. Methods: Elderly patients (n = 78) with LS‐SCLC were divided into three groups depending on the timing of radiotherapy. The patients in the TRT group were stratified into early (TRT after 1–2 cycles of chemotherapy, n = 29), medium‐term (TRT after 3–4 cycles of chemotherapy, n = 33), and late (TRT after 5–6 cycles of chemotherapy, n = 16) TRT groups. The overall survival (OS) and progression‐free survival (PFS) were assessed and compared. Results: The medium‐term TRT group demonstrated significantly longer mPFS (20.12 months) and better mOS (35.97 months) than those in the other groups (PFS: P = 0.021;OS: P = 0.035). A pairwise comparison of the three groups revealed that those who received medium‐term TRT exhibited significantly improved PFS than the early (mPFS: 20.12 vs. 10.36 mouths, P = 0.018) and late (mPFS: 20.12 vs. 9.17 months, P = 0.016) TRT. The medium‐term TRT group demonstrated significantly improved OS than the early TRT (mOS: 35.97 vs. 25.22 months, P = 0.007) but not in comparison with the late TRT (mOS: 35.97 vs. 21.63 months, P = 0.100). Conclusion: In elderly patients with LS‐SCLC, the addition of TRT after 3–4 cycles of chemotherapy appears to be a viable and potentially beneficial treatment approach. [ABSTRACT FROM AUTHOR]

Background Specific components of lipid profile seem to differently impact on immune activity against cancer and unraveling their prognostic role in patients with solid cancer treated with immune checkpoint inhibitors (ICIs) is needed. Materials and Methods We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile (total cholesterol [TC], triglycerides [TG], low-density lipoproteins [LDL], high-density lipoproteins [HDL]) of patients with consecutive solid cancer treated with ICIs, and we investigated their role in predicting clinical outcomes. Results At a median follow-up of 32.9 months, among 430 enrolled patients, those with TC ≥ 200 mg/dl showed longer median progression-free survival (mPFS; 6.6 vs. 4.7 months, P  = .4), although not reaching statistical significance, and significantly longer median overall survival (mOS; 19.4 vs. 10.8 months, P  = .02) compared to those with TC < 200 mg/dl. Conversely, patients with TG ≥150 mg/dl displayed shorter PFS (3.4 vs. 5.1 months, P  = .02) and OS (7.1 vs. 12.9 months, P  = .009) compared to those with TG <150 mg/dl. TC and TG were then combined in a "LIPID score" identifying three subgroups: good-risk (GR) (TC ≥200 mg/dl and TG <150 mg/dl), intermediate-risk (IR) (TC <200 mg/dl and TG <150 mg/dl or TC ≥200 mg/dl and TG ≥150 mg/dl) and poor-risk (PR) (TC <200 mg/dl and TG ≥150 mg/dl). The mPFS of GR, IR, and PR groups was 7.8, 4.3, and 2.5 months, respectively (P  = .005); mOS of GR, IR, and PR was 20.4, 12.4, and 5.3 months, respectively (P  < .001). At multivariable analysis, the PR profile represented an independent poor prognostic factor for both PFS and OS. Conclusions We developed a lipid score that defined subgroups of patients with cancer who differently benefit from ICIs. Further mechanistic insights are warranted to clarify the prognostic and predictive role of lipid profile components in patients treated with ICIs. [ABSTRACT FROM AUTHOR]

Simple Summary: Although ATE + BEV treatment provides improved therapeutic efficacy, in our study, high-risk populations such as patients with grade Vp4 portal vein thrombus, bile duct invasion, or more than 50% liver infiltration had poor responses. This study aimed to investigate real-world outcomes and prognostic factors in high-risk patients with advanced HCC treated with atezolizumab plus bevacizumab. Unlike what was reported in the IMbrave150 study, atezolizumab plus bevacizumab treatment had consistent efficacy and tolerability in both the total and high-risk population in our study. Radiation therapy combined with atezolizumab plus bevacizumab treatment might be helpful to improve progression-free survival and overall survival in high-risk groups. Real-world data regarding treatment with atezolizumab plus bevacizumab in high-risk patients with advanced HCC are lacking. In this multicenter retrospective cohort study, a total of 215 patients with advanced HCC received atezolizumab plus bevacizumab treatment at four tertiary hospitals. High-risk patients were those with grade Vp4 portal vein thrombus, bile duct invasion, or more than 50% liver infiltration. In total, 98 (45.6%) were the high-risk population, 186 (86.5%) were considered to be Child–Pugh class A, and 128 (59.5%) had previously received neoadjuvant or concomitant radiation treatment. Median overall survival (OS) was 11.25 months (95% CI, 9.50–13.10), and the median progression-free survival (PFS) was 8.00 months (95% CI, 6.82–9.18). In the high-risk population, the median OS was 10 months (95% CI, 8.19–11.82) and the median PFS was 6.50 months (95% CI, 3.93–9.08). In the high-risk population, multivariate analysis indicated that radiation therapy and lower ALBI grade were associated with better OS and PFS. A total of 177 (82.3%) patients experienced adverse events of any grade, the most common being proteinuria (23.7%). Atezolizumab plus bevacizumab treatment showed consistent efficacy and tolerability in both the total and high-risk population. Radiation therapy combined with atezolizumab plus bevacizumab treatment might be helpful to improve PFS and OS in high-risk populations. [ABSTRACT FROM AUTHOR]

Simple Summary: Scalp irradiation for cutaneous malignancies presents complex challenges due to the high radiation dose, irregular surface anatomy, and radiosensitive organs at risk. Scalp convexity provides unique aspects to consider when attempting to deliver a homogenous dose with external beam radiation. Traditional bolus methods face several issues, including the risk of air gaps and placement difficulty due to skull shape. Here, we outline the steps involved with 3D-milled bolus creation, which has the potential to deliver a homogenous dose to the surface target with rapid dose falloff when treated with VMAT radiation. To our knowledge, this is the first study to report clinical outcomes using this approach. We showed homogenous dose target coverage and OAR doses lower than those reported in other studies utilizing alternative dose delivery and bolus techniques. We also showed that while acute skin toxicity was substantial, the treatment was well tolerated in later follow-up with only 5% late grade 3 toxicity. Background and purpose: A bolus is required when treating scalp lesions with photon radiation therapy. Traditional bolus materials face several issues, including air gaps and setup difficulty due to irregular, convex scalp geometry. A 3D-milled bolus is custom-formed to match individual patient anatomy, allowing improved dose coverage and homogeneity. Here, we describe the creation process of a 3D-milled bolus and report the outcomes for patients with scalp malignancies treated with Volumetric Modulated Arc Therapy (VMAT) utilizing a 3D-milled bolus. Materials and methods: Twenty-two patients treated from 2016 to 2022 using a 3D-milled bolus and VMAT were included. Histologies included squamous cell carcinoma (n = 14, 64%) and angiosarcoma (n = 8, 36%). A total of 7 (32%) patients were treated in the intact and 15 (68%) in the postoperative setting. The median prescription dose was 66.0 Gy (range: 60.0–69.96). Results: The target included the entire scalp for 8 (36%) patients; in the remaining 14 (64%), the median ratio of planning target volume to scalp volume was 35% (range: 25–90%). The median dose homogeneity index was 1.07 (range: 1.03–1.15). Six (27%) patients experienced acute grade 3 dermatitis and one (5%) patient experienced late grade 3 skin ulceration. With a median follow-up of 21.4 months (range: 4.0–75.4), the 18-month rates of locoregional control and overall survival were 75% and 79%, respectively. Conclusions: To our knowledge, this is the first study to report the clinical outcomes for patients with scalp malignancies treated with the combination of VMAT and a 3D-milled bolus. This technique resulted in favorable clinical outcomes and an acceptable toxicity profile in comparison with historic controls and warrants further investigation in a larger prospective study. [ABSTRACT FROM AUTHOR]

Background: Despite the significant weight of difficulty, Ethiopia's survival rate and mortality predictors have not yet been identified. Finding out what influences outpatient breast cancer patients' survival time was the major goal of this study. Methods: A retrospective study was conducted on outpatients with breast cancer. In order to accomplish the goal, 382 outpatients with breast cancer were included in the study using information obtained from the medical records of patients registered at the University of Gondar referral hospital in Gondar, Ethiopia, between May 15, 2016, and May 15, 2020. In order to compare survival functions, Kaplan-Meier plots and the log-rank test were used. The Cox-PH model and Bayesian parametric survival models were then used to examine the survival time of breast cancer outpatients. The use of integrated layered Laplace approximation techniques has been made. Results: The study included 382 outpatients with breast cancer in total, and 148 (38.7%) patients died. 42 months was the estimated median patient survival time. The Bayesian Weibull accelerated failure time model was determined to be suitable using model selection criteria. Stage, grade 2, 3, and 4, co-morbid, histological type, FIGO stage, chemotherapy, metastatic number 1, 2, and >=3, and tumour size all have a sizable impact on the survival time of outpatients with breast cancer, according to the results of this model. The breast cancer outpatient survival time was correctly predicted by the Bayesian Weibull accelerated failure time model. Conclusions: Compared to high- and middle-income countries, the overall survival rate was lower. Notable variables influencing the length of survival following a breast cancer diagnosis were weight loss, invasive medullar histology, comorbid disease, a large tumour size, an increase in metastases, an increase in the International Federation of Gynaecologists and Obstetricians stage, an increase in grade, lymphatic vascular space invasion, positive regional nodes, and late stages of cancer. The authors advise that it is preferable to increase the number of early screening programmes and treatment centres for breast cancer and to work with the public media to raise knowledge of the disease's prevention, screening, and treatment choices. [ABSTRACT FROM AUTHOR]

Background: Non‐small cell lung cancer (NSCLC) is often diagnosed at an advanced stage. Clinical trials have demonstrated that first‐line immunotherapy alone or in combination with chemotherapy improves overall survival. However, reports of survival outcomes in real‐world settings are limited. We assessed survival in advanced NSCLC patients treated with immunotherapy alone or in combination with chemotherapy in first‐ or second‐line at the Windsor Regional Cancer Program (WRCP) and compared it to existing literature. Methods: We included patients diagnosed with stage IV NSCLC from January 2015 to December 2020 and treated with first‐line chemoimmunotherapy (ChemoImmuno1), chemotherapy followed by immunotherapy (Chemo1), or immunotherapy followed by chemotherapy (Immno1) in our survival analysis. Patients with oncogene‐addicted mutations were excluded. Results: There were 160 patients of which 41.5% were female. Mean age was 68 years. Median overall survival from time of diagnosis was 474 days (95% CI: 249, 949) with an estimated 5‐year survival of 11.1% (95% CI: 4.5, 21.3). Median OS in ChemoImmuno1 was 9.6 months, in Chemo1 was 19.2 months from time of diagnosis and 10.5 months from time of initiation of immunotherapy, and in Immuno1 was 18.4 months, respectively. Estimated survival at three years from time of diagnosis for ChemoImmuno1 was 17.6% and for Immuno1 was 17.9%. For Chemo1, from diagnosis it was 20.1% and from second‐line therapy it was 15.4%. Survival outcomes were comparable to clinical trials and other studies. Conclusion: Real‐world survival outcomes of immunotherapy for advanced NSCLC are comparable to the existing literature in this single center study. [ABSTRACT FROM AUTHOR]

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

Simple Summary: Liver resection for colorectal liver metastases (CRLM) with major vessel involvement is challenging and valid data on outcomes are still lacking. We analyzed data of 32 hepatectomies combined with 35 major hepatic vessel resections and reconstructions with special regard to surgical approaches, histopathological findings and outcome. The vena cava inferior was resected and reconstructed in 19, the portal vein in 6 and a hepatic vein in 10 cases. Histology confirmed a vascular infiltration in 6/32 patients. In conclusion, liver resections with vascular resection/reconstruction are rare, but can be performed with low morbidity and mortality and histological vessel infiltration occurs seldom. Background: Treatment of CRLM with major vessel involvement is still challenging and valid data on outcomes are still rare. We analyzed our experience of hepatectomies with resection and reconstruction of major hepatic vessels with regard to operative and perioperative details, histopathological findings and oncological outcome. Methods: Data of 32 hepatectomies with major hepatic vessel resections and reconstructions were included. Results were correlated with perioperative and oncological outcome. Results: Out of 1236 surgical resections due to CRLM, we performed 35 major hepatic vessel resections and reconstructions in 32 cases (2.6%) during the study period from January 2008 to March 2023. The vena cava inferior (VCI) was resected and reconstructed in 19, the portal vein (PV) in 6 and a hepatic vein (HV) in 10 cases. Histopathological examination confirmed a vascular infiltration in 6/32 patients (VCI 3/17, HV 2/10 and PV 1/6). There were 27 R0 and 5 R1 resections. All R1 situations affected the parenchymal margin. Vascular wall margins were R0. Ninety-day mortality was 0. The median overall survival (OS) for the patient group with vascular infiltration (V1) was 21 months and for the V0 group 33.3 months. Conclusion: Liver resections with vascular resection and reconstruction are rare and histological vessel infiltration occurs seldom. In cases with presumed vascular wall infiltration, liver resection combined with major vessel resection and reconstruction can be performed with low morbidity and mortality. We prefer a parenchymal sparing liver resection with vascular resection and reconstruction to achieve negative resection margins, but in technically difficult cases with higher risk for postoperative complications, tumor detachment from vessels without resection is a most reasonable surgical alternative. [ABSTRACT FROM AUTHOR]

Simple Summary: Crizotinib, an oral tyrosine kinase inhibitor that targets ALK, MET, and ROS1 kinase, has emerged as an effective treatment for ROS1-rearranged NSCLC. In South Korea's real-world setting, characterized by a higher elderly population and increased brain/central nervous system metastasis rates, crizotinib remains a cornerstone in treating ROS1-rearranged NSCLC, providing lasting clinical benefits with a favorable safety profile. Liquid biopsies, utilizing biomarkers, are instrumental in detecting targetable mutations, monitoring the disease burden, and identifying resistance mechanisms. In our study, next-generation sequencing using cell-free total nucleic acids enables the detection of ROS1 fusions and the identification of resistance mechanisms during disease progression. Real-world data on the use and outcomes of crizotinib in ROS1-rearranged non-small-cell lung cancer (NSCLC) are limited. This study aims to analyze the real-world efficacy of crizotinib in South Korea and explore the utilization of liquid biopsies that implement next-generation sequencing (NGS) using cell-free total nucleic acids. In this prospective multicenter cohort study, 40 patients with ROS1-rearranged NSCLC, either starting or already on crizotinib, were enrolled. Patients had a median age of 61 years, with 32.5% presenting brain/central nervous system (CNS) metastases at treatment initiation. At the data cutoff, 48.0% were still in treatment; four continued with it even after disease progression due to the clinical benefits. The objective response rate was 70.0%, with a median duration of response of 27.8 months. The median progression-free survival was 24.1 months, while the median overall survival was not reached. Adverse events occurred in 90.0% of patients, primarily with elevated transaminases, yet these were mostly manageable. The NGS assay detected a CD74–ROS1 fusion in 2 of the 14 patients at treatment initiation and identified emerging mutations, such as ROS1 G2032R, ROS1 D2033N, and KRAS G12D, during disease progression. These findings confirm crizotinib's sustained clinical efficacy and safety in a real-world context, which was characterized by a higher elderly population and higher rates of brain/CNS metastases. The study highlights the clinical relevance of liquid biopsy for detecting resistance mechanisms, suggesting its value in personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Combined serplulimab and chemotherapy demonstrated improved clinical survival outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) and PD-L1 combined positive scores (CPS) ≥ 1. The present study aimed to evaluate the economic viability of integrating serplulimab in combination with chemotherapy as a potential therapeutic approach for treating ESCC in China. Methods: A Markov model was constructed to evaluate the economic and health-related implications of combining serplulimab with chemotherapy. With the incremental cost-effectiveness ratio (ICER), costs and results in terms of health were estimated. For assessing parameter uncertainty, one-way and probabilistic sensitivity studies were carried out. Results: The combination of serplulimab and chemotherapy yielded incremental costs and QALYs of $3,163 and 0.14, $2,418 and 0.10, and $3,849 and 0.15, respectively, for the overall population as well as patients with PD-L1 CPS1-10 and PD-L1 CPS ≥ 10. This corresponds to ICER values per QALY of $23,657, $23,982, and $25,134. At the prespecified WTP limit, the probabilities of serplulimab with chemotherapy being the preferred intervention option were 74.4%, 61.3%, and 78.1% for the entire patient population, those with PD-L1 1 ≤ CPS < 10, and those with PD-L1 CPS ≥ 10, respectively. The stability of the presented model was confirmed through sensitivity studies. Conclusions: In conclusion, the combination of Serplulimab and chemotherapy showed excellent cost-effectiveness compared to chemotherapy alone in treating PD-L1-positive patients with ESCC in China. [ABSTRACT FROM AUTHOR]

Background: Associations between adjuvant chemotherapy (ACT) and the improvement in survival for patients with pT2N0M0 non‐small cell lung cancer (NSCLC) who received R0 resection remain controversial. This study aimed to evaluate the value of ACT for patients with pT2N0M0 NSCLCs, and to identify the subgroups who could benefit from ACT. Methods: Multivariable Cox proportional hazards regression models were used to estimate independent prognostic factors. High‐risk factor (HRF) included visceral pleural invasion (VPI), lymphovascular invasion (LVI) and poor differentiation/undifferentiated tumors. Results: Of the 899 patients, 277 (30.8%) patients received ACT. More younger patients (p < 0.001) and male patients (p = 0.007) received ACT. With the increase of pathological tumor size (p < 0.001) and the number of HRFs (p < 0.001), there was a significant rise in the proportion of patients receiving ACT. For all patients, ACT could not improve recurrence‐free survival (RFS) (p = 0.672) and overall survival (OS) (p = 0.306). For patients with pathological stage IIA or radiological pure‐solid tumors, ACT could significantly improve the OS (p = 0.011 and p = 0.037, respectively), and multivariate analysis revealed that ACT was an independent prognostic factor for patients with pathological stage IIA (p = 0.005). ACT could improve the OS significantly in patients with pathological stage IB pure‐solid lung adenocarcinoma (LUAD) (p = 0.043). Conclusion: ACT was valuable for patients with pathological stage IIA (pT2bN0M0) and patients with radiological pure‐solid LUAD of pathological stage IB. A combination of radiological features and pathological subtypes could be helpful when selecting patients with pT2N0M0 NSCLCs for ACT. [ABSTRACT FROM AUTHOR]

Simple Summary: Molecular targeted therapies are very effective as a treatment for postoperative recurrence of non-small cell lung cancer (NCSLC) with driver mutations. On the other hand, the efficacy of local therapies for oligo-recurrence has also been reported. To investigate the optimal treatment strategy for oligo-recurrence in NSCLC patients with driver mutations, we retrospectively evaluated 66 NSCLC patients with driver mutations who were treated with local or molecular targeted therapies as the initial treatment after recurrence. Patients treated with local therapies as a first-line treatment did not show statistically significant differences in post-recurrence survival and progression-free survival compared with those treated with molecular targeted therapies. However, local therapies as an initial treatment should be considered preferably, as they can be curative after recurrence and can delay the start of the administration of molecular targeted therapies. Background: The efficacy of local therapies for lung cancer patients with postoperative oligo-recurrence has been reported. However, whether local therapies should be chosen over molecular targeted therapies for oligo-recurrence patients with driver mutations remains controversial. Therefore, we aimed to investigate the optimal initial treatment strategy for oligo-recurrence in lung cancer patients with driver mutations. Methods: Among 2152 patients with lung adenocarcinoma who underwent surgical resection at our institute between 2008 and 2020, 66 patients with driver mutations who experienced cancer oligo-recurrence after surgery and were treated with local or molecularly targeted therapy as an initial therapy after recurrence were evaluated. Oligo-recurrence was characterized by the presence of 1 to 3 recurrent lesions. These patients were investigated, focusing on their post-recurrence therapies and prognoses. Results: The median follow-up period was 71 months. Local and molecular targeted therapies were administered to 41 and 25 patients, respectively. The number of recurrence lesions tended to be lower in the initial local therapy group than in the molecular targeted therapy group. In the initial local therapy group, 23 patients (56%) subsequently received molecular targeted therapies. The time from recurrence to the initiation of molecular targeted therapy was significantly longer in the local therapy group than in the molecular targeted therapy group (p < 0.001). There was no significant difference in post-recurrence overall survival (hazard ratio, 1.429; 95% confidence interval, 0.701–2.912; log-rank, p = 0.324) and post-recurrence progression-free survival (hazard ratio, 0.799; 95% confidence interval, 0.459–1.390; log-rank, p = 0.426) in the initial local ablative therapy group compared with the initial molecular targeted therapy group. Conclusions: Local therapies as a first-line treatment did not show statistically significant differences in post-recurrence survival or progression-free survival compared with molecular targeted therapies. However, local therapies as an initial treatment should be considered preferably, as they can cure the recurrence and can delay the start of administration of molecular targeted therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Debate exists regarding the effect of D2 vs. D1 lymphadenectomy on long-term oncological outcomes after gastrectomy for cancer. The aim of our individual patient data meta-analysis was to assess the impact of D2 lymphadenectomy on long-term survival after gastrectomy for gastric cancer. Compared with previous randomized trials, we confirmed a trend toward improved overall survival (1.8 months; 95% CI −4.2, 0.7; p = 0.14), cancer specific survival (1.2 months, 95% CI −3.9, 5.7; p = 0.72), and disease-free survival (0.8 months, 95% CI −1.7, 3.4; p = 0.53) at 60-month follow-up for D2 lymphadenectomy. Compared to D1, D2 lymphadenectomy is associated with a clinical trend toward improved OS, CSS, and DFS at 60-month follow-up. Background: Debate exists concerning the impact of D2 vs. D1 lymphadenectomy on long-term oncological outcomes after gastrectomy for cancer. Methods: PubMed, MEDLINE, Scopus, and Web of Science were searched and randomized controlled trials (RCTs) analyzing the effect of D2 vs. D1 on survival were included. Overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were assessed. Restricted mean survival time difference (RMSTD) and 95% confidence intervals (CI) were used as effect size measures. Results: Five RCTs (1653 patients) were included. Overall, 805 (48.7%) underwent D2 lymphadenectomy. The RMSTD OS analysis shows that at 60-month follow-up, D2 patients lived 1.8 months (95% CI −4.2, 0.7; p = 0.14) longer on average compared to D1 patients. Similarly, 60-month CSS (1.2 months, 95% CI −3.9, 5.7; p = 0.72) and DFS (0.8 months, 95% CI −1.7, 3.4; p = 0.53) tended to be improved for D2 vs. D1 lymphadenectomy. Conclusions: Compared to D1, D2 lymphadenectomy is associated with a clinical trend toward improved OS, CSS, and DFS at 60-month follow-up. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have dramatically shifted the therapeutic paradigm of extensive‐stage small cell lung cancer (ES‐SCLC). Antibiotic (ATB) exposure before or during ICI therapy can harm the integrity of the gut microbiome and lead to intestinal dysbiosis, which has a profoundly negative impact on the treatment response for various malignancies. Whether this is applicable to ES‐SCLC remains unclear. Methods: We retrospectively reviewed the electronic medical records of all patients diagnosed with ES‐SCLC who were treated with ICI‐based immunotherapies from July 2019 to December 2020 at Shandong Cancer Hospital and Institute, China. Outcomes with the use of ATBs before or after the first infusion of ICI, including progression‐free survival (PFS) and overall survival (OS), were investigated using the Kaplan–Meier method. Multivariate analyses were also conducted using a Cox proportional hazards model. Results: A total of 214 patients were included, among whom 41 (19.2%) received ATBs within 2 months before or after the first initiation of ICI therapy and were assigned to the ATB group. The ATB group showed a shorter median PFS (4.3 vs. 6.3 months; HR = 1.43, 95% CI: 0.97–2.11; p = 0.043) and a significantly shorter median OS (6.9 vs. 13 months; HR = 1.47, 95% CI: 0.98–2.20; p = 0.033) than the non‐ATB group. In the multivariate analysis, ATB exposure was markedly associated with worse PFS (HR = 1.47, 95% CI: 1.03–2.09, p = 0.035) and OS (HR = 1.46, 95% CI: 1.01–2.11, p = 0.043). Conclusions: Our results demonstrate that ATB exposure was significantly associated with worse survival in ES‐SCLC patients who received ICI therapy. [ABSTRACT FROM AUTHOR]