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Objectives: Socioeconomic factors affect oncologic outcome in sinonasal squamous cell carcinoma (SNSCC). However, the relationship between these factors and stage at presentation (SAP)-a critical, early point in the care cycle-is not known. This study sought to determine the role of race/ethnicity, treatment facility type, insurance status/carrier, and other socioeconomic factors in SAP and survival among patients with advanced SNSCC., Study Design: Retrospective cohort study., Methods: Using the National Cancer Database, 6,155 patients with SNSCC were identified and divided into those with "early" (Stage I or II; 2,212 (35.9%)) versus "advanced" (Stage III or IV; 3,943 (64.1%)) disease. Associations between sociodemographic and socioeconomic factors on SAP and survival were analyzed using multivariable logistic regression and Cox proportional hazard models., Results: Black (odds ratio [OR]: 2.18, CI: 1.74-2.76), Asian and Pacific Islander (API) (OR: 2.37, CI: 1.43-4.14), and Medicaid or uninsured (OR: 2.04, CI: 1.66-2.53) patients were more likely to present with advanced disease. Among patients with advanced disease, API patients demonstrated the highest 10-year survival rate (30.2%), and Black patients had the lowest 2-, 5-, and 10-year survival rates (47.7%, 31.9% and 19.2%, respectively). Older age (HR:1.03, CI:1.03-1.04), Black race (HR:1.39, CI:1.21-1.59), Medicaid or uninsured status (HR:1.48, CI:1.27-1.71), and treatment at a community hospital (HR:1.25, CI:1.14-1.37) were associated with poorer overall survival among patients with advanced disease., Conclusions: Factors including race/ethnicity, treatment facility type, insurance status/carrier, and other socioeconomic factors influence SAP and survival in SNSCC. An improved understanding of how these factors relate to outcomes may elucidate opportunities to address gaps in education and access to care in vulnerable populations., Level of Evidence: 4 Laryngoscope, 131:2421-2428, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Head and neck cancers (HNC) are relatively fast-growing tumours, and delay in treatment initiation is associated with tumour progression and adverse outcome. An overview of factors contributing to delay can provide critical insights on necessary adjustments to optimize care pathways. This systematic review aims to identify factors associated with delay and summarize the effect of delay on oncological outcome measures., Methods: A search strategy was conducted according to PRISMA guidelines to search electronic databases for studies assessing the carepathway interval (days between first visit in head and neck oncology center and treatment initiation) and/or time-to-treatment-initiation interval (days between histological diagnosis and treatment initiation) and 1) determinants of delay and/or 2) effect of delay on outcome within these timeframes. Due to heterogeneity between included studies, a meta-analysis was not possible., Results: Fifty-two studies were eligible for quantitative analysis. Non-Caucasian race, academic setting, Medicaid/no insurance and radiotherapy as primary treatment were associated with delay. Advanced tumour stage was related to increased time-to-treatment initiation in the four common sites combined (oral cavity, oropharynx, hypopharynx, larynx). Separate determinants for delay in different tumour locations were identified. In laryngeal, oral cavity cancer and the four common HNC sites combined, delay in start of treatment is associated with decreased overall survival, although no cut-off time point could be determined., Conclusion: Race, facility type, type of insurance and radiotherapy as primary treatment were associated with delay and subsequent inferior survival in the four common sites combined., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Local recurrences (LR) and distant metastases (DM) are common in retroperitoneal soft tissue sarcoma (RPS). Longer time to recurrence and resection of the recurrent lesion have been identified as beneficial prognostic factors for overall survival (OS) upon first tumor relapse. However, prognostic factors concerning OS upon subsequent recurrences are scarcely defined. In this study, we aimed to identify prognostic factors for post-relapse outcome in multiple recurrent RPS., Methods: Patients undergoing resection of primary and recurrent RPS at the University Hospital Heidelberg were retrospectively analyzed. Multivariable Cox regression analyses were performed to identify predictors of overall, LR- and DM-free survival. Subgroup analyses were performed for liposarcoma and leiomyosarcoma patients., Results: 201 patients with primary disease, 101 patients with first, 66 patients with second and 43 patients with third LR as well as 75 patients with DM were analyzed. More than 12 months to recurrence and resection of recurrence were associated with improved OS after resection of first and second LR (5-year OS for first/second LR; resection: 64%/62%, no resection: 20%/46%). Gross macroscopic incomplete resection of first (p < 0.001), second (p = 0.001), and third recurrences (p < 0.001) was an independent prognostic factor for poor OS., Conclusion: Development of LR and DM is frequent in RPS. Once a tumor relapsed, patients benefit from tumor resection not only in case of first, but also in case of subsequent recurrences., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives/hypothesis: The purpose of this study was to investigate survival differences between low-grade and high-grade sinonasal adenocarcinoma (SNAC) by examining demographics, tumor characteristics, and treatment modalities., Study Design: Retrospective database analysis., Methods: The National Cancer Database was queried for patients with SNAC between 2004 and 2015. Univariate and multivariate analyses were performed for all cases of SNAC. Subsequent analysis focused on low-grade (grade 1 and grade 2) and high-grade (grade 3 and grade 4) SNAC., Results: A total of 1,288 patients with SNAC were included in the main cohort and divided into low grade (n = 601) and high grade (n = 370). The 5-year overall survival for all patients, low-grade, and high-grade was 54%, 64%, and 38%, respectively. Prognostic factors associated with decreased survival for the main cohort include advanced age (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.03-1.06), Charlson-Deyo score (HR: 1.37; 95% CI: 1.05-1.78), grade 2 (HR: 2.21; 95% CI: 1.26-3.86], grade 3 (HR: 3.67; 95% CI: 2.09-6.45), and grade 4 (HR: 3.31; 95% CI: 1.38-7.91). Radiotherapy was associated with improved overall survival for high-grade SNAC (HR: 0.41; 95% CI: 0.24-0.70) but not for low-grade SNAC (HR: 1.05; 95% CI: 0.59-1.85)., Conclusions: This investigation is the largest to date analyzing the association of treatment modalities with overall survival in SNAC. Surgery remains paramount to treatment, with radiotherapy offering additional survival benefit for high-grade SNAC. Administration of chemotherapy was not associated with improved survival., Level of Evidence: 4 Laryngoscope, 130:E1-E10, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Disease-free survival (DFS) is increasingly being used as surrogate end-point for overall survival (OS) in cancer trials. So far, there has been no validation of the surrogacy of DFS for OS for neoadjuvant treatment of gastroesophageal adenocarcinoma., Methods: The study uses individual patient data (IPD) from eight randomised controlled trials (RCTs) (n = 1126 patients) comparing neoadjuvant therapy followed by surgery with surgery alone for gastroesophageal adenocarcinoma. Correlation between OS time and DFS time was calculated to evaluate individual-level surrogacy. For each trial, survival curves using the Kaplan-Meier method were plotted and hazard ratios (HRs) on the treatment effects were calculated for OS and DFS separately. Those HRs were pooled in a random-effects meta-analysis. Observed HRs were compared with predicted HRs for OS using results from an error-in-variables linear regression model accounting for the uncertainty about the estimated effect. The strength of the association was quantified by the coefficient of determination to assess trial-level surrogacy. The surrogate threshold effect was calculated to determine the minimum treatment effect on DFS necessary to predict a non-zero treatment effect on OS., Results: A strong correlation between OS time and DFS time was observed, indicating a high individual-level surrogacy. For all RCTs, estimated HRs for OS and DFS were highly similar. In the meta-analysis, the overall HR for OS was virtually identical to that for DFS. The estimated coefficient of determination r 2 for the association between HRs for OS and DFS was 0.912 (95% confidence interval: 0.75-1.0), indicating a very good fit of the regression model and thus a strong trial-level surrogacy between OS and DFS. The surrogate threshold effect based on the regression analysis was 0.79., Discussion: Based on strong correlations between DFS and OS, as well as a strong correlation of the treatment effects of the two end-points in the error-in-variable regression, DFS seems an appropriate surrogate marker for OS in randomised trials of neoadjuvant chemotherapy or chemoradiotherapy for gastroesophageal adenocarcinoma., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Our aim was to evaluate the prognostic impact of three inflammatory markers - neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and lymphocyte monocyte ratio (LMR) - on overall survival (OS) in older adults with cancer., Materials and Methods: Our sample includes 144 patients age ≥ 65 years with solid tumor cancer who completed a cancer-specific Geriatric Assessment (GA) from 2010 to 2014 and had pretreatment CBC with differential. NLR was dichotomized a previously reported cut-off value of 3.5, while PLR and LMR were dichotomized at the median. Cox proportional hazards models evaluated whether NLR, PLR and LMR were predictive of OS independent of covariates including a recently developed 3-item GA-derived prognostic scale consisting of (1) "limitation in walking several blocks", (2) "limitation in shopping", and (3) "≥ 5% unintentional weight loss in 6 months"., Results: Median age was 72 years, 53% had breast cancer, 27% had stage 4 cancer, 14% had Karnofsky Performance Status (KPS) < 80, 11% received less intensive than standard treatment for stage, and 39% had NLR > 3.5. In univariable analysis, higher NLR and PLR and lower LMR were significantly associated with worse OS. NLR remained a significant predictor of OS (HR = 2.16, 95% CI; 1.10-4.25, p = .025) after adjusting for cancer type, stage, age, KPS, treatment intensity, and the GA-derived prognostic scale., Conclusion: NLR > 3.5 is predictive of poorer OS in older adults with cancer, independent of traditional prognostic factors and the GA-derived prognostic scale., (Copyright © 2018. Published by Elsevier Ltd.)

Objectives The aim of our study has been to determine the association between the appearance of infection after modified posterior pelvic exenteration (MPE) and TTC (time to adjuvant chemotherapy) and to examine whether the infection impacts clinical results by delaying the start of chemotherapy. Material and methods The present, retrospective study analyzed 77 patients who had undergone MPE followed by adjuvant chemotherapy. Either no residual tumor or tumor less than 2.5 mm was achieved in 76.7% of these patients. Patients were divided into two subgroups for comparison; the first group consisted of 41 patients with infections, the second group of 36 patients without infections. Infection after surgery was monitored within a 90-day postoperative period. Median TTC and OS (overall survival) was determined for those patients who developed infection as well as for those who did not. Results The expected 5-year survival rate was 0.40 (SD=0.09) for those patients without infection and 0.17 (SD=0.07) for those patients with infection. The survival curves of patients with infection and those without infection were statistically significantly different (p=0.038). Median TTC differed significantly for those patients who developed infection vs those patients who did not develop infection (37days vs 27.5 days, p=0.024), and patients without infection were statistically more likely to receive chemotherapy within 25 days following surgery than in the subsequent 25-42-day period compared to those patients who did develop infection (p=0.048). No statistically significant differences were found between the groups in relation to the initiation of chemotherapy within 42 days (p=0.445). Conclusions The absence of postoperative infection was associated with a better survival. Patients with infection were noted a longer time interval from surgery to start of chemotherapy without negative impact to OS.

Background: In previous studies, correlation between overall survival (OS) and surrogate endpoints like objective response rate (ORR) or progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) was poor. This can be biased by crossover and postprogression treatments., Objectives: To evaluate the relationship between these two surrogate endpoints and OS in advanced NSCLC studies that did not allow for crossover or reported balanced post-progression treatments., Methods: A systematic review in patients with advanced NSCLC receiving second- and further-line therapy was performed. The relationship between the absolute difference in ORR or median PFS (mPFS) and the absolute difference in median OS (mOS) was assessed using the correlation coefficient (R) and weighted regression models. The analysis was repeated in predefined data cuts based on crossover and balance of postprogression treatments. When the upper limit of R's 95% confidence interval (CI) was more than 0.7, the surrogate threshold effect (STE) was estimated., Results: In total, 146 randomized clinical trials (43,061 patients) were included. The mean ORR, mPFS, and mOS were 12.2% ± 11.2%, 3.2 ± 1.3 months, and 9.6 ± 4.1 months, respectively. The correlation coefficients of ORR and mPFS were 0.181 (95% CI 0.016-0.337) and 0.254 (95% CI 0.074-0.418), respectively, with mOS. Nevertheless, in trials that did not allow crossover and reported balanced postprogression treatments, the correlation coefficients of ORR and mPFS were 0.528 (95% CI 0.081-0.798) and 0.778 (95% CI 0.475-0.916), respectively, with mOS. On the basis of STE estimation, in trials showing significant treatment effect size of 41.0% or more ORR or 4.15 or more mPFS months, OS benefit can be expected with sufficient certainty., Conclusions: Crossover and postprogression treatments may bias the relationship between surrogate endpoints and OS. Presented STE calculation can be used to interpret treatment effect on either ORR or PFS when used as primary endpoints., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: The real-world occurrence rate of non-breast cancer-specific death (non-BCSD) and its impact on patients with breast cancer are poorly recognized., Methods: Women with resectable breast cancer from 1990 to 2007 in the Surveillance, Epidemiology, and End Results database (n = 199,963) were analyzed. The outcome events of breast cancer were classified as breast cancer-specific death (BCSD), non-BCSD, or survival. Binary logistics was used to estimate the occurrence rates of non-BCSD and BCSD with different clinicopathological factors. The Gray method was used to measure the cumulative incidence of non-BCSD and BCSD. The ratio of non-BCSDs to all causes of death and stacked cumulative incidence function plots were used to present the impact of non-BCSD on overall survival (OS). Models of Cox proportional hazards regression and competing risk regression were compared to highlight the suitable model., Results: There were 12,879 non-BCSDs (6.44%) and 28,784 BCSDs (14.39%). The oldest age group (>62 years), black race, and a single or divorced marital status were associated with more non-BCSDs. With adjustments for age, a hormone receptor-positive (HoR+) status was no longer related to increased non-BCSDs. In patients with grade 1, stage I disease and an HoR+ status as well as the oldest subgroup, a great dilution of non-BCSD on all causes of death could be observed, and this led to incorrect interpretations. The inaccuracy, caused by the commonly used Cox proportional hazards model, could be corrected by a competing risk model., Conclusions: OS was largely impaired by non-BCSD during early breast cancer. For some future clinical trial planning, especially for the oldest patients and those with HoR+ breast cancer, non-BCSD should be considered a competing risk event. Cancer 2017;123:2432-43. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: Overall survival (OS) is considered the gold standard for determining treatment efficacy in oncology trials, but the relation between treatment and OS can be challenging to assess because of long study durations and the impact of subsequent therapies on outcome. Using OS can be particularly difficult for new therapies in hematologic malignancies (HMs)., Methods: This retrospective analysis was conducted to characterize the primary endpoints used to support US Food and Drug Administration (FDA) approvals for new drug or novel HM indications between January 2002 and July 2015. Data on approvals were retrieved from the FDA and CenterWatch websites, and from the FDA prescribing information on respective products at the time of approval., Results: Sixty-three FDA approvals involving 35 drugs and 16 HMs were identified. Of the 63 approvals, 45 (71.4%) included response rate (RR), and 17 (27%) included progression-free survival (PFS; n = 14) or time to progression (n = 3), and 1 approval included OS. Twenty-three approvals (36.5%) included trials with an active comparator arm. The median relative magnitude of benefit versus comparator was 71% improvement (range, 26%-127%), with a median hazard ratio of 0.55 (range, 0.16-0.72)., Conclusions: FDA approvals for new drug or novel HM indications are often based on endpoints other than OS, such as RR and PFS. Tools for determining the magnitude of clinical benefit and treatment value in HMs should take into account the importance of RR, PFS, and other non-OS endpoints. Cancer 2017;123:1689-1694. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Purpose: To compare the disease-free survival (DFS) and overall survival (OS) rates of men and women undergoing treatment for breast cancer., Methods: A retrospective cohort study of patients with breast cancer diagnosed and treated at the Cancer Hospital III of the National Cancer Institute of Brazil, Rio de Janeiro, Brazil, between 1999 and 2013. Male breast cancer cases were matched for age, year of diagnosis, and clinical staging to three female cases (1:3). Patient characteristics were abstracted from hospital records and medical charts. Cases were analyzed using descriptive statistics, and comparisons between the genders were performed using Kaplan-Meier curves and Cox regression analysis with 95% confidence intervals., Results: The study population comprised 98 men and 294 women. There were significant differences (p < 0.05) between the genders for marital status, alcohol consumption, smoking, presence of hypertension and other comorbidities, histological type of tumor, expression of estrogen receptors, progesterone receptors, human epidermal growth factor receptor-type 2, type of breast surgery, neoadjuvant chemotherapy, adjuvant radiotherapy, and use of palliative bisphosphonate therapy. Five- and 10-year DFS rates were, respectively, 80.0 and 51.4% for men and 71.4 and 63.5% for women (p = 0.245), and 5- and 10-year OS rates were, respectively, 65.0 and 47.5% for men and 56.5 and 41.4% for women (p = 0.221)., Conclusion: There was no significant difference in prognosis (DFS and OS rates) between the genders, but significant differences in sociodemographic and clinical characteristics were detected between male and female breast cancer cases.

Background: Approximately 190,000 Americans are diagnosed with non-small cell lung cancer (NSCLC) annually, and about half have metastatic (Stage IV) disease. These patients have historically had poor survival prognosis, but several new therapies introduced since 2000 provide options for improved outcomes. The objectives of this study were to quantify survival gains from 1990, when best supportive care (BSC) only was standard, to 2015 and to estimate the impact of expanded use of systemic therapies in clinically appropriate patients., Materials and Methods: We developed a simulation model to estimate survival gains for patients with metastatic NSCLC from 1990-2015. Survival estimates were derived from major clinical trials and extrapolated to a lifetime horizon. Proportions of patients receiving available therapies were derived from the Surveillance, Epidemiology, and End Results database and a commercial treatment registry. We also estimated gains in overall survival (OS) in scenarios in which systemic therapy use increased by 10% and 30% relative to current use., Results: From 1990-2015, one-year survival proportion increased by 14.1% and mean per-patient survival improved by 4.2 months (32,700 population life years). Increasing treated patients by 10% or 30% increased OS by 5.1 months (39,700 population life years) and 6.9 months (53,800 population life years), respectively., Conclusion: Although survival remains poor in metastatic NSCLC relative to other common cancers, meaningful progress in per-patient and population-level outcomes has been realized over the past 25 years. These advances can be improved even further by increasing use of systemic therapies in the substantial proportion of patients who are suitable for treatment yet who currently receive BSC only. The Oncologist 2017;22:304-310 IMPLICATIONS FOR PRACTICE: Approximately 93,500 Americans are diagnosed with metastatic non-small cell lung cancer (NSCLC) annually. Historically, these patients have had poor survival prognosis, but newer therapies provide options for improved outcomes. This simulation modeling study quantified metastatic NSCLC survival gains from 1990-2015. Over this period, the one-year survival proportion and mean per-patient survival increased by 14.1% and 4.2 months, respectively. Though metastatic NSCLC survival remains poor, the past 25 years have brought meaningful gains. Additional gains could be realized by increasing systemic therapy use in the substantial proportion of patients who are suitable for treatment, yet currently receive only supportive care., (© AlphaMed Press 2017.)

Purpose: PFS is often used as a surrogate endpoint for OS in metastatic breast cancer studies. We have evaluated the association of treatment effect on PFS with significant HR OS (and how this association is affected by other factors) in published prospective metastatic breast cancer studies., Methods: A systematic literature search in PubMed identified prospective metastatic breast cancer studies. Treatment effects on PFS were determined using hazard ratio (HR PFS ), increase in median PFS (ΔMED PFS ) and % increase in median PFS (%ΔMED PFS ). Diagnostic accuracy of PFS measures (HR PFS , ΔMED PFS and %ΔMED PFS ) in predicting significant HR OS was assessed using receiver operating characteristic (ROC) curves and classification tree approach (CART)., Results: Seventy-four cases (i.e., treatment to control comparisons) from 65 individual publications were identified for the analyses. Of these, 16 cases reported significant treatment effect on HR OS at 5% level of significance. Median number of deaths reported in these cases were 153. Area under the ROC curve (AUC) for diagnostic measures as HR PFS , ΔMED PFS and %ΔMED PFS were 0.69, 0.70 and 0.75, respectively. Classification tree results identified %ΔMED PFS and number of deaths as diagnostic measure for significant HR OS . Only 7.9% (3/39) cases with ΔMED PFS shorter than 48.27% reported significant HR OS . There were 7 cases with ΔMED PFS of 48.27% or more and number of deaths reported as 227 or more - of these 5 cases reported significant HR OS ., Conclusion: %ΔMED PFS was found to be a better diagnostic measure for predicting significant HR OS . Our analysis results also suggest that consideration of total number of deaths may further improve its diagnostic performance. Based on our study results, the studies with 50% improvement in median PFS are more likely to produce significant HR OS if the total number of OS events at the time of analysis is 227 or more., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To report on the follow-up of two previously published RCTs on the performance of screw-retained monolithic zirconia restorations on titanium (ti)-base abutments based on either digital scans through intraoral optical scanning (IOS) or conventional impressions. Materials and Methods: A total of 54 patients receiving 89 restorations (44 solitary crowns [SC], 21 splinted crowns [2-FDP], and 24 three-unit fixed partial dentures [3-FDP]) were included for the 1- to 3-year follow-up period. Restoration survival and technical complications were documented. Results: In total, 50 patients with 84 restorations completed the 3-year follow-up. One 3-FDP from the digital group was lost. This resulted in a survival rate of 97.9% for the digital group and 100% for the conventional group and an overall survival rate of 98.8% for screw-retained monolithic zirconia restorations on implants after 3 years. There was no statistically significant survival difference between the digital and conventional restorations (P = .362). When evaluated separately, a 100% survival rate of SCs and 97.7% for 2-FDPs could be reported. One decementation and three screw loosenings occurred in the 1- to 3-year follow-up. The multiple-implant restorations showed higher (23.3%) complication rates at the restoration level than the SCs (4.9%) after 3 years of function (P = .026). Conclusions: Screw-retained monolithic zirconia restorations on ti-base abutments show promising survival rates after 3 years of function. Restorative complications in screw-retained monolithic zirconia restorations on Ti-base abutments are more likely to happen in the first year of function and are more common in multiple-implant restorations than SCs. The impression type (digital or conventional) does not seem to influence these results. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Limited information is available regarding the impact of sarcopenia on the prognosis of antiangiogenic therapy in individuals with advanced non‐small cell lung cancer (NSCLC). This study primarily sought to examine the prognostic significance of sarcopenia in individuals with advanced NSCLC undergoing antiangiogenic therapy.We retrospectively enrolled all patients who met the inclusion and exclusion criteria from 2019 to 2021 at Nantong University Hospital. Patients were grouped according to the presence or absence of sarcopenia. After propensity score matching (PSM), progression‐free survival (PFS), overall survival (OS), and adverse event rates were compared between the two groups. Factors associated with prognosis were screened using univariate and multivariate analyses.A total of 267 patients were included, with a total of 201 matched at baseline after PSM (77 in the sarcopenia group and 124 in the non‐sarcopenia group). The sarcopenia group had lower PFS (p = 0.043) and OS (p = 0.011) than the non‐sarcopenia group and a higher incidence of adverse events (p = 0.044). Multivariate analysis suggested that sarcopenia is an independent prognostic risk factor for OS in advanced NSCLC patients receiving antiangiogenic therapies (p = 0.009). Results of subgroup analyses showed some differences in the impact of sarcopenia on survival prognosis in populations with different characteristics.Patients with advanced NSCLC with comorbid sarcopenia exhibit a worse prognosis when treated with antiangiogenic therapy, and preventing and ameliorating sarcopenia may lead to better survival outcomes in patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

Objectives: This study was performed to investigate the detection rate of EGFR T790M mutation by repeated rebiopsy, to identify the clinical factors related to repeated rebiopsy, and to assess survival outcomes according to the methods and numbers of repeated rebiopsies in patients with lung adenocarcinoma who received sequential osimertinib after failure of previous 1st or 2nd generation EGFR-tyrosine kinase inhibitors. Methods: This retrospective study included patients with advanced-stage lung adenocarcinoma who were confirmed to have EGFR T790M mutation and to have received osimertinib from January 2020 to February 2021 at Samsung Medical Center. The presence of T790M mutation was assessed based on either plasma circulating tumor DNA (ctDNA) or tissue specimens. Results A total of 443 patients underwent rebiopsy, with 186 (42.0%) testing positive for the T790M mutation by the sixth rebiopsy. The final analysis included 143 eligible patients. Progression-free survival was not significantly different in terms of the methods (tissue: 13.3 months, 95% confidence interval [CI]: [9.4, 23.5] vs plasma: 11.1 months, 95% CI: [8.1, 19.4], p = 0.33) and numbers (one: 13.4 months, 95% CI: [9.4, 23.5] vs two or more: 11.0 months, 95% CI: [8.1, 14.8], p = 0.51) of repeated rebiopsies. Longer overall survival (OS) was found in patients in whom T790M was detected by tissue specimens rather than by plasma ctDNA (2-year OS rate: 81.7% for tissue vs 63.9% for plasma, p = 0.0038). Factors related to the lower numbers of rebiopsies included age and bone metastasis. Factor associated with T790M detection in tissue rather than in plasma was pleural metastasis, while advanced tumor stage was related to T790M confirmation in plasma rather than in tissue. Conclusions: Repeated rebiopsy for T790M detection in patients with NSCLC can increase the detection rate of the mutation. Detection of T790M by plasma ctDNA might be related to poor survival outcomes. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Carcinoembryonic antigen (CEA) is one of the commonly used preoperative biomarkers for colorectal cancer (CRC), but no meta‐analysis has evaluated the findings of all recently published studies to determine whether its postoperative level can serve as a prognostic indicator.We conducted a systematic search for eligible literature from the PubMed, EMBASE, and Web of Science databases in October 2023. Studies that investigated the relationship between postoperative serum CEA levels and prognosis in CRC patients were included. Outcome indicators, including overall survival (OS), disease‐free survival (DFS), and progression‐free survival (PFS)/recurrence‐free survival (RFS), were analyzed using a fixed‐effects or random‐effects model. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values.This meta‐analysis included 20 eligible studies involving 10,114 CRC patients from the East Asian and Western countries. A comprehensive analysis revealed that elevated postoperative CEA levels were associated with low OS (HR: 2.92, 95% CI: 2.36–3.62, and p < 0.000), DFS (HR: 2.81, 95% CI: 2.01–3.94, and p < 0.000), and RFS/PFS (HR: 2.52, 95% CI: 1.75–3.62, p < 0.000). A subgroup analysis by region, analysis type, distant metastasis, HR obtain method, sample size, postoperative measurement date, and study design demonstrated that the negative correlation observed between high serum CEA levels after surgery and poor prognosis was not significantly different between the subgroups.When CEA levels are found to be elevated during postoperative follow‐up, more active intervention measures should be implemented to further improve the patient's survival outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) patients beyond the Milan criteria (MC) who undergo liver resection have high recurrence rates and poor prognosis, and sometimes experience very early recurrence (VER) within six months after surgery. This study aimed to identify predictive factors, including the newly proposed C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index, for VER after surgery for HCC beyond MC. Methods: We included patients who underwent initial liver resection for HCC beyond MC between 2000 and 2021. We defined VER as recurrence within six months after surgery and compared the clinicopathological factors and long-term prognosis between the VER and non-VER groups. Multivariate analysis identified risk factors for VER and evaluated the potential for prognostic stratification using these factors. Results: The overall survival (OS) and post-recurrence survival were significantly worse in the VER group compared to patients with recurrence in 7–12 months, over 12 months, and without recurrence (median survival time (MST) 1.16 vs. 5.14, 7.26, and undefined; and MST 0.81 vs. 4.34, and 5.48, respectively, P < 0.01). Alpha-fetoprotein (AFP) ≥ 200, non-simple nodule (SN) type on preoperative imaging, and CALLY index < 2.8 were independent prognostic factors (P < 0.01 for all). An increased risk factor count was correlated with poorer VER and OS rates, allowing for effective stratification. Conclusion: VER after hepatic resection for HCC beyond MC was associated with a significantly poorer prognosis. AFP, non-SN type on imaging, and CALLY index are valuable preoperative indicators. Patients with multiple risk factors have a worse prognosis and may be candidates for multimodal treatment. [ABSTRACT FROM AUTHOR]

Objective: We explored the preliminary value of abnormal spindle-like microcephaly- associated (ASPM) protein in aiding precise risk sub-stratification, prediction of metabolic heterogeneity, and prognosis of neuroblastoma (NB). Methods: This retrospective study enrolled newly diagnosed patients with NB who underwent positron emission tomography/computed tomography (PET/CT) before therapy, and tumor tissue was collected after surgery. Regression analysis was used to evaluate ASPM expression and risk stratification in patients with NB. The expression levels of ASPM, clinical information, and PET/CT text features were analyzed using univariate and multivariate survival analyses. Finally, a correlation analysis was used to explore the relationship between ASPM and tumor metabolic heterogeneity. Results: There were 48 patients with NB in this study (35 boys and 13 girls); 22 patients progressed and 16 died. We found that the level of ASPM was highly associated with risk stratification (OR = 5.295, 95%IC: 1.348–41.722, p = 0.021). Patients with NB and high-risk stratification with high ASPM level had a lower 3-year progression-free survival (PFS) rate (14.28%) and 1-year PFS rate (57.14%) than those with low ASPM level (57.14% and 93.75%, respectively). Using univariate and multivariate survival analyses, this study revealed that ASPM and LDH were independent risk factors for both PFS and overall survival (OS), whales GLZLM_ZLNU was only a risk factor for PFS. Conclusion: ASPM holds promise as a novel biomarker for refining current risk stratification and predicting prognosis in neuroblastoma. Elevated levels of ASPM, LDH, and GLZLM_ZLNU may be associated with poorer survival outcomes in neuroblastoma patients. [ABSTRACT FROM AUTHOR]

The systemic immune-inflammatory index (SII) has been identified as an independent prognostic factor for multiple diseases. However, the impact of SII on outcome of acute-on-chronic liver failure (ACLF) is scant. A retrospective study enrolled patients with ACLF treated with artificial liver support system. Restricted cubic spline (RCS) (knots at the 10th, 50th, and 90th percentiles) and Cox proportional hazards models were applied to investigate the relationship between SII and 90-day transplant-free survival and overall survival in patients with ACLF. A total of 258 patients with ACLF were included. The 90-day transplant-free survival rate and overall survival rate were 58.5% and 66.3%. The SII was 465.5 (277.3–804.4). Adjusted RCS models showed linear exposure–response relationship between SII and 90-day transplant-free survival (P for overall < 0.001, P for nonlinear = 0.154) and 90-day overall survival (P for overall < 0.001, P for nonlinear = 0.103), and adjusted Cox models confirmed the positive relationship. Compared with patients with SII < 480, patients with ≥ 480 had more serious condition, lower 90-day transplant-free survival rate (46.8% vs. 69.7%, adjusted HR (95% CI) for transplant or death: 2.13 (1.40–3.23), P < 0.001), and lower 90-day overall survival rate (56.3% vs. 75.8%; adjusted HR (95% CI) for death: 2.26 (1.42–3.61), P = 0.001). Stratified Cox models suggested no potential modifiers in the relationship between SII and 90-day transplant-free survival. Our findings suggested SII was positively associated with poor short-term prognosis of ACLF. [ABSTRACT FROM AUTHOR]

Background: Patients with relapsed primary mediastinal nonseminomatous germ cell tumor have low cure rates with salvage chemotherapy or surgery. The authors report survival outcomes of patients who received high‐dose chemotherapy (HDCT) and peripheral blood stem cell transplantation (PBSCT) at Indiana University. Methods: The prospectively maintained Indiana University germ cell tumor database identified 32 patients with primary mediastinal nonseminomatous germ cell tumor who progressed after first‐line cisplatin‐based combination chemotherapy and received HDCT and PBSCT between 2006 and 2021. Therapy included two consecutive courses of HDCT consisting of 700 mg/m2 carboplatin and 750 mg/m2 etoposide, each for 3 consecutive days, and each followed by PBSCT. A second course was not given if the patient experienced progressive disease or prohibitive toxicity. Progression‐free survival and overall survival were analyzed using the Kaplan–Meier method. Medians with 95% confidence intervals were also calculated along with 2‐year probabilities. Results: The median age at HDCT was 30 years (range, 18–61 years). With a median follow‐up of 4.7 years (range, 1–14 years), the 2‐year progression‐free survival rate was 31% (95% confidence interval, 16%–47%), and the 2‐year overall survival rate was 35% (95% confidence interval, 19%–52%). At last follow‐up, nine patients (28%) remained without evidence of disease, including two platinum‐refractory patients and two patients who were receiving HDCT as third‐line therapy. There were three treatment‐related deaths. Conclusions: Salvage HDCT and PBSCT is an active combination in patients who have relapsed primary mediastinal nonseminomatous germ cell tumor with curative potential and prolonged survival, including in platinum‐refractory and third‐line settings. The authors recommend this approach for initial salvage chemotherapy in this patient population. Patients who have relapsed primary mediastinal nonseminomatous germ cell tumors have poor outcomes with salvage chemotherapy. The authors report the results of high‐dose chemotherapy and peripheral blood stem cell transplantation, which permit more rapid succession to the subsequent cycle and potentially improved efficacy compared with historical regimens. [ABSTRACT FROM AUTHOR]

Background: Evaluating outcome reliability is critical in real-world evidence studies. Overall survival is a common outcome in these studies; however, its capture in real-world data (RWD) sources is often incomplete and supplemented with linked mortality information from external sources. Conflicting recommendations exist for censoring overall survival in real-world evidence studies. This simulation study aimed to understand the impact of different censoring methods on estimating median survival and log hazard ratios when external mortality information is partially captured. Methods: We used Monte Carlo simulation to emulate a non-randomized comparative effectiveness study of two treatments with RWD from electronic health records and linked external mortality data. We simulated the time to death, the time to last database activity, and the time to data cutoff. Death events after the last database activity were attributed to linked external mortality data and randomly set to missing to reflect the sensitivity of contemporary real-world data sources. Two censoring schemes were evaluated: (1) censoring at the last activity date and (2) censoring at the end of data availability (data cutoff) without an observed death. We assessed the performance of each method in estimating median survival and log hazard ratios using bias, coverage, variance, and rejection rate under varying amounts of incomplete mortality information and varying treatment effects, length of follow-up, and sample size. Results: When mortality information was fully captured, median survival estimates were unbiased when censoring at data cutoff and underestimated when censoring at the last activity. When linked mortality information was missing, censoring at the last activity date underestimated the median survival, while censoring at the data cutoff overestimated it. As missing linked mortality information increased, bias decreased when censoring at the last activity date and increased when censoring at data cutoff. Conclusions: Researchers should consider the completeness of linked external mortality information when choosing how to censor the analysis of overall survival using RWD. Substantial bias in median survival estimates can occur if an inappropriate censoring scheme is selected. We advocate for RWD providers to perform validation studies of their mortality data and publish their findings to inform methodological decisions better. [ABSTRACT FROM AUTHOR]

Objective Patients and Methods Results Conclusions To investigate the influence of statins on the survival outcomes of patients with non‐muscle‐invasive bladder cancer (NMIBC) treated with adjuvant intravesical bacille Calmette‐Guérin (BCG) immunotherapy.A retrospective cohort of consecutive patients with NMIBC who received intravesical BCG therapy from 2001 to 2020 and statins prescription were identified. Overall survival (OS), cancer‐specific survival (CSS), recurrence‐free survival (RFS), and progression‐free survival (PFS) were analysed between the Statins Group vs No‐Statins Group using Kaplan–Meier method and multivariable Cox regression.A total of 2602 patients with NMIBC who received intravesical BCG were identified. The median follow‐up was 11.0 years. On Kaplan–Meier analysis, the Statins Group had significant better OS (P < 0.001), CSS (P < 0.001), and PFS (P < 0.001). Subgroup analysis indicated statins treatment started before BCG treatment had better CSS (P = 0.02) and PFS (P < 0.01). Upon multivariable Cox regression analysis, the ‘statins before BCG’ group was an independent protective factor for OS (hazard ratio [HR] 0.607, 95% confidence interval [CI] 0.514–0.716), and CSS (HR 0.571, 95% CI 0.376–0.868), but not RFS (HR 0.885, 95% CI 0.736–1.065), and PFS (HR 0.689, 95% CI 0.469–1.013).Statins treatment appears to offer protective effects on OS and CSS for patients with NMIBC receiving adjuvant intravesical BCG. [ABSTRACT FROM AUTHOR]

Background: Cancer is a complex disease, caused and impacted by a combination of genetic, demographic, clinical, environmental and lifestyle factors. Analysis of cancer characteristics, risk factors, treatment options and the heterogeneity across cancer types has been the focus of medical research for years. The aim of this study is to describe and summarise genetic, clinicopathological, behavioural and demographic characteristics and their differences across ten common cancer types and evaluate their impact on overall survival outcomes. Methods: This study included data from 9977 patients with bladder, breast, colorectal, endometrial, glioma, leukaemia, lung, ovarian, prostate, and renal cancers. Genetic data collected through the 100,000 Genomes Project was linked with clinical and demographic data provided by the National Cancer Registration and Analysis Service (NCRAS), Hospital Episode Statistics (HES) and Office for National Statistics (ONS). Descriptive and Kaplan Meier survival analyses were performed to visualise similarities and differences across cancer types. Cox proportional hazards regression models were applied to identify statistically significant prognostic factor associations with overall survival. Results: 161 clinical and 124 genetic factors were evaluated for prognostic association with overall survival. Of these, 116 unique factors were found to have significant prognostic effect for overall survival across ten cancer types when adjusted for age, sex and stage. The findings confirmed prognostic associations with overall survival identified in previous studies in factors such as multimorbidity, tumour mutational burden, and mutations in genes BRAF, CDH1, NF1, NRAS, PIK3CA, PTEN, TP53. The results also identified new prognostic associations with overall survival in factors such as mental health conditions, female health-related conditions, previous hospital encounters and mutations in genes FANCE, FBXW7, GATA3, MSH6, PTPN11, RB1, RNF43. Conclusion: This study provides a comprehensive view of clinicopathological and genetic prognostic factors across different cancer types and draws attention to less commonly known factors which might help produce more precise prognosis and survival estimates. The results from this study contribute to the understanding of cancer disease and could be used by researchers to develop complex prognostic models, which in turn could help predict cancer prognosis more accurately and improve patient outcomes. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsPrevious studies have reported inconsistent results on the association between serum prealbumin level and survival outcomes in patients with gastric cancer. This meta-analysis aimed to determine the serum prealbumin level as a biomarker of survival outcomes in gastric cancer patients.Two independent reviewers conducted a thorough search of PubMed, Embase, and Web of Science databases until April 17, 2024. Studies reporting the association between serum prealbumin level and survival outcomes and presented the multivariable-adjusted relative risks for gastric cancer patients were included. The pooled HR and 95% CI were used to assess the strength of the association.Twelve studies, with a total of 9,351 patients were included in the meta-analysis. The combined data showed that low serum prealbumin level was associated with shorter overall survival (HR 1.65; 95% CI 1.42-1.91) and disease-free survival (HR 1.39; 95% CI 1.14-1.70). Subgroup analysis showed that low serum prealbumin level significantly predicted poorer overall survival, regardless of patients’ age, sample sizes, cutoff value for prealbumin level, and follow-up time.Low serum prealbumin level is an independent prognostic biomarker for shorter survival outcomes in patients with gastric cancer. Assessing serum prealbumin levels could potentially improve risk stratification for this disease. [ABSTRACT FROM AUTHOR]

Liver grafts from controlled donation after circulatory death (cDCD) donors have lower utilization rates due to inferior graft and patient survival rates, largely attributable to the increased incidence of ischemic cholangiopathy, when compared with grafts from brain dead donors (DBD). Normothermic regional perfusion (NRP) may improve the quality of cDCD livers to allow for expansion of the donor pool, helping to alleviate the shortage of transplantable grafts. A systematic review and metanalysis was conducted comparing NRP cDCD livers with both non-NRP cDCD livers and DBD livers. In comparison to non-NRP cDCD outcomes, NRP cDCD grafts had lower rates of ischemic cholangiopathy [RR = 0.23, 95% CI (0.11, 0.49), p = 0.0002], primary non-function [RR = 0.51, 95% CI (0.27, 0.97), p = 0.04], and recipient death [HR = 0.5, 95% CI (0.36, 0.69), p < 0.0001]. There was no difference in outcomes between NRP cDCD donation compared to DBD liver donation. In conclusion, NRP improved the quality of cDCD livers compared to their non-NRP counterparts. NRP cDCD livers had similar outcomes to DBD grafts. This provides further evidence supporting the continued use of NRP in cDCD liver transplantation and offers weight to proposals for its more widespread adoption. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B, often leading to Hepatocellular carcinoma (HCC), poses a major global health challenge. While Tenofovir (TDF) and Entecavir (ETV) are potent treatments, their comparative effectiveness in improving recurrence-free survival (RFS) and overall survival (OS) rates in HBV-related HCC is not well-established. Methods: We conducted an individual patient data meta-analysis using survival data from randomized trials and high-quality propensity score-matched studies to compare the impact of Tenofovir (TDF) and Entecavir (ETV) on RFS and OS in HBV-related HCC patients. Data from six databases and gray literature up to 30 August 2023, were analyzed, utilizing Kaplan-Meier curves, stratified Cox models, and shared frailty models for survival rate assessment and to address between-study heterogeneity. The study employed restricted mean survival time analysis to evaluate differences in RFS and OS between TDF-treated and ETVtreated patients. Additionally, landmark analyses compared early (<2 years) and late (≥2 years) tumor recurrence in these cohorts. Results: This study incorporated seven research articles, covering 4,602 patients with HBV-related HCC (2,082 on TDF and 2,520 on ETV). Within the overall cohort, TDF recipients demonstrated significantly higher RFS (p = 0.042) and OS (p < 0.001) than those on ETV. The stratified Cox model revealed significantly improved OS for the TDF group compared to the ETV group (hazard ratio, 0.756; 95% confidence interval, 0.639-0.896; p = 0.001), a result corroborated by the shared frailty model. Over a follow-up period of 1-8 years, no significant difference was noted in the mean time to death between the TDF and ETV groups. The rates of early recurrence did not significantly differ between the groups (p = 0.735). However, TDF treatment was significantly associated with a reduced risk of late recurrence compared to ETV (p < 0.001). In the HCC resection subgroup, the disparities in OS, early, and late recurrence rates between the two treatments paralleled those seen in the overall cohort. Conclusion: Compared to ETV, TDF may enhance OS and reduce late tumor recurrence risk in HBV-related HCC patients receiving curative treatment. However, there was no statistically significant distinction in the timing of tumor recurrence and mortality between patients administered TDF and those prescribed ETV. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions One‐third of head and neck squamous cell carcinomas are early‐stage oral cavity squamous cell carcinomas (OCSCC). Despite a high curative rate, 20% of early‐stage OCSCC patients do not achieve long‐term survival. This study evaluates the role of adjuvant therapy (ADJ) in delaying disease progression and prolonging survival.This single‐institute retrospective cohort study enrolled 481 early‐stage OCSCC patients, 16% (78/481) of whom received ADJ. It was reported according to the STROBE guidelines. Cox proportional hazards regression and Kaplan–Meier survival curves were employed to identify suitable candidates for ADJ.The 5‐year locoregional recurrence‐free survival (LR‐RFS) and overall survival rates were 73.2% and 84.9%, respectively. Positive margins and advanced depth of invasion (DOI) were independent predictors of LR‐RFS. For patients with positive margins, adjuvant chemoradiotherapy (CRT) was superior to adjuvant radiotherapy alone in improving LR‐RFS (hazard ratios for adjuvant CRT vs. none, 0.042; adjuvant radiotherapy alone vs. none, 0.702). Excluding positive margins, advanced DOI was the most critical factor in assessing the need for ADJ. Positive margins and advanced DOI were more appropriate criteria than EORTC 22931/RTOG 9501 for evaluating adjuvant CRT.Adjuvant CRT was indicated for patients with positive margins and advanced DOI to improve survival outcomes. [ABSTRACT FROM AUTHOR]

Summary Aim Methods Results Conclusions This study aims to investigate the predictive factors for conversion therapy in patients with unresectable hepatocellular carcinoma (uHCC) and to evaluate the prognosis of conversion cases by comparing them with partial response (PR) and complete response (CR) cases.In this retrospective multicentre study, we included a total of 946 uHCC patients treated with atezolizumab and bevacizumab (Atez/Bev) from September 2020 to September 2023.Out of the patients, 43 (4.5%) received conversion therapy following Atez/Bev treatment. The overall response rate was 65.1% and 23.7% in the conversion and non‐conversion group, respectively, with a statistical significance (p < 0.001). Multivariate analyses identified that BCLC stage B or an earlier stage (p = 0.045), absence of macrovascular invasion and extrahepatic spread (p = 0.045), and a low value of neutrophil to lymphocyte ratio (p = 0.04) were significantly favourable predictive factors associated with conversion therapy. The conversion group showed significantly better survival compared to the non‐conversion group (p < 0.001). In the landmark analysis at 6, 12 and 18 months, the conversion group exhibited better survival compared to PR patients in the non‐conversion group (p = 0.04, 0.01 and 0.03, respectively) and there were no significant differences in the overall survival (OS) between the conversion group and patients who achieved a CR (p = 0.7, 1.0 and 0.3, respectively).Patients with low tumour burden and low value of NLR were more likely to undergo conversion therapy. The OS of patients undergoing conversion therapy showed better survival compared to those achieving PR and was comparable to those with CR patients. Conversion therapy could be considered if feasible. [ABSTRACT FROM AUTHOR]

Background and Aims Methods Results Conclusions It has been described that recompensation can improve prognosis in patients with cirrhosis. However, recompensation after transjugular intrahepatic portosystemic shunt (TIPS) has not been studied. We evaluated the impact of recompensation after TIPS on the risk of hepatocellular carcinoma (HCC) and death, and we compared it with compensated cirrhosis patients.An observational study of consecutive patients with cirrhosis undergoing TIPS between 2008 and 2022 was performed. Baveno VII definition of recompensation was used including patients with or without diuretics/Hepatic encephalopathy prophylaxis. A prospective cohort of consecutive compensated cirrhosis patients was used for comparison.Overall, 208 patients with cirrhosis were included, 92 compensated and 116 decompensated who underwent TIPS. After 1 year, 24% achieved recompensation. Liver function (MELD 12 ± 5 vs. 15 ± 6; p = .049), LDL‐cholesterol (97 mg/dL vs. 76 mg/dL, p = .018), white cell count (7.96 × 109/dL vs. 6.24 × 109/dL, p = .039) and platelets (129 × 109/dL vs. 101 × 109/dL, p = .039) were associated with recompensation. Recompensation was associated with a reduction in the risk of HCC (p = .020). Multivariable analysis showed that this risk was significantly higher in non‐recompensated patients (p = .003) but no differences were observed in recompensated compared with compensated patients (p = .816). Similarly, decompensated patients presented lower survival rates (p = .011), while no differences were observed between recompensated and compensated patients (p = .677).Recompensation after TIPS has a clear impact on the incidence of HCC and death, with a similar prognosis than patients with compensated cirrhosis. Liver function is associated with recompensation, suggesting the importance of considering early TIPS in patients with indication. [ABSTRACT FROM AUTHOR]

Background: While Heat Shock Protein 60 (HSP60) has been linked to human tumor, its clinic significance specifically in breast carcinoma is unclear. This investigation aims to retrospectively evaluate how HSP60 protein levels relate to survival outcomes among patients diagnosed with breast carcinoma. Methods: Evaluation of 206 patients diagnosed with breast carcinoma and receiving treatment from January 2012 to April 2018, carried out retrospectively. The protein level of HSP60 in breast carcinoma determined by immunohistochemical. Results: The study provided evidence of a distinct upregulation of HSP60 expression in breast carcinoma tumor samples in contrast to adjacent normal tissue samples. Additionally, heightened HSP60 expression was linked to advanced T stage (P = 0.046), N stage (P = 0.034), tumor metastasis (P = 0.016), pathological grading (P = 0.012), and adjuvant therapy utilization (P = 0.004). Moreover, elevated levels of HSP60 proteins exhibited a significant inverse correlation with overall survival (OS) [hazard ratio (HR) 1.598, P = 0.018] and progression-free survival (PFS) (HR 1.600, P = 0.017) among breast carcinoma patients in univariate analyses. The results of multivariate analyses highlighted HSP60 may serve as an independent predictor for both OS and PFS in breast carcinoma patients (HR 1.525, P = 0.034; HR 1.528, P = 0.033, respectively). Conclusion: The involvement of HSP60 in breast carcinoma progression suggests its potential clinical relevance in treatment target validation and prognostic assessment of the disease. [ABSTRACT FROM AUTHOR]

Background: The therapeutic advantage of thoracic radiotherapy (tRT) as an adjunct to first‐line immunotherapy and chemotherapy in patients with extensive‐stage small cell lung cancer (ES‐SCLC) remains unclear. We sought to elucidate this in a retrospective cohort study comparing the effectiveness and safety of tRT in combination with first‐line immunotherapy and chemotherapy. Methods: Our retrospective study included patients with ES‐SCLC, treated at the West China Hospital between January 2019 and December 2022. They received first‐line immunotherapy and chemotherapy and were categorized into two cohorts based on the administration of tRT. The primary outcomes were overall survival (OS) and progression‐free survival (PFS). Cox regression analysis was utilized to identify potential independent predictors of prognosis and to compare the treatment outcomes across various patient subgroups. Treatment‐related toxicities across both cohorts were compared using the Chi‐squared test. Results: A total of 99patients were eligible for the study, out of which 55 received tRT. The medianduration of follow‐up was 39 months. Remarkably, patients who received tRTdemonstrated superior OS and PFS in comparison to those who did not (P < 0.05). Subgroup analysis further confirmed these findings. Multivariate analysisidentified treatment group and liver metastasis as independent prognosticfactors (P < 0.05). The incidence of grade 3‐4 adverse events showed nostatistically significant difference between the two cohorts. Conclusions: Thus, weconfirmed that the addition of tRT to the conventional regimen of first‐linechemotherapy and immunotherapy yields better survival outcomes without asignificant increase in toxicity. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate whether inosine enhances the efficacy of immune‐checkpoint inhibitors in human malignant solid tumors. Methods: This single‐center, prospective, randomized, open‐label study was conducted, from January 2021 to December 2022, in Beijing Friendship Hospital, Capital Medical University, and participants were randomly assigned (1:1) to either the inosine (trial) or non‐inosine (control) group that received inosine (dosage: 0.2 g, three times/day) + PD‐1/PD‐L1 inhibitor or only PD‐1/PD‐L1 inhibitor ± targeted ± chemotherapy, respectively. Efficacy was assessed every 6 weeks (i.e., after every two–three treatment cycles). The primary endpoint was the objective response rate (ORR); the secondary endpoints were disease control rate, overall survival (OS), and progression‐free survival (PFS). The trial was registered at ClinicalTrials.gov (NCT05809336). Results: Among the 172 participants with advanced malignant solid tumors, 86 each were assigned to the inosine and non‐inosine groups, wherein the median PFS (95% CI) was 7.00 (5.31–8.69) and 4.40 (3.10–5.70) months, respectively (hazard ratio [HR] 0.63; 95% CI 0.44–0.90, p = 0.011), and the ORR was 26.7% and 15.1%, respectively (p = 0.061). In the inosine and non‐inosine groups, the median OS was not reached and was 29.67 (95% CI 17.40–41.94) months, respectively (HR 1.05 [95% CI 0.59–1.84], p = 0.874). Compared with the non‐inosine group, the median PFS and ORR of the inosine group were significantly prolonged and improved in the multiple exploratory subgroup analyses. The safety analysis showed that Grades 3 and 4 adverse reactions occurred in 25 (29%) and 31 (36%) patients in the inosine and non‐inosine groups, respectively, and tended to decrease in the inosine group compared with the non‐inosine group. Conclusion: Inosine had a tendency to enhance the efficacy of immune‐checkpoint inhibitors and reduced immunotherapy‐related adverse reactions. Compared with the control group, the median progression‐free survival was significantly prolonged and the objective response rate tended to increase in the inosine group. Inosine has a tendency to enhance the efficacy of immune‐checkpoint inhibitors and reduce immunotherapy‐related adverse reactions in clinical applications. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to analyse the outcomes of patients with large B‐cell lymphoma (LBCL) treated with chimeric antigen receptor T‐cell therapy (CAR‐Tx), with a focus on outcomes after CAR T‐cell failure, and to define the risk factors for rapid progression and further treatment. Methods: We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd‐line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022. Results: The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate. The median progression‐free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively. Sixty‐three patients (59%) were refractory or relapsed after CAR‐Tx. Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%). The median follow‐up of surviving patients in whom treatment failed was 10.6 months. Several factors predicting further treatment administration and outcomes were present even before CAR‐Tx. Risk factors for not receiving further therapy after CAR‐Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P. The median OS‐2 (from R/P after CAR‐Tx) was 6.7 months (6‐month 57.9%) for treated patients and 0.4 months (6‐month 4.2%) for untreated patients (p < 0.001). The median PFS‐2 (from R/P after CAR‐Tx) was 3.2 months (6‐month 28.5%) for treated patients. The risk factors for a shorter PFS‐2 (n = 39) included: CRP > limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P. All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS‐2 for treated patients. Conclusion: Our findings allow better stratification of CAR‐Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement). [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety, tolerability, and preliminary efficacy of multiple doses of pegylated irinotecan (JK1201I) as a second‐line monotherapy for treating small‐cell lung cancer (SCLC) patients. Methods: According to the "3 + 3" dose‐escalation principle, patients received intravenous JK1201I at 180 or 220 mg/m2 once every 3 weeks for four cycles. Progression‐free survival (PFS), overall survival (OS), median progression‐free survival (mPFS), and median overall survival (mOS) were evaluated. The Kaplan–Meier method was used to analyze PFS and overall OS. Brookmeyer and Crowley's method was used for mPFS and mOS. Results: This study included 29 patients with stage III–IV SCLC (stage IIIa, n = 1; stage IIIb, n = 1; and stage IV, n = 27). Of these, 26 patients were enrolled in the 180 mg/m2 dose group, and 3 patients were enrolled in the 220 mg/m2 dose group. No dose‐limiting toxicity (DLT) was noted during the first 28 days of treatment. Grade 3 or higher adverse events were recorded in the 180 mg/m2 group, including diarrhea (11.5%, 3/26), neutropenia (7.7%, 2/26), and leukopenia (7.7%, 2/26). In the 220 mg/m2 group, one patient (33.3%, 1/3) experienced neutropenia or leukopenia. In the 180 mg/m2 group, 38.5% (10/26) of patients achieved an objective response rate (ORR), with a disease control rate (DCR) of 73.1% (19/26). The mPFS and mOS were 3.4 and 12.1 months, respectively. In the 220 mg/m2 group, one patient had stable disease, and one had progressive disease (PD). The ORR, DCR, mPFS, and mOS were 0% (0/3) and 33.3% (1/3), 2.7 months and 2.7 months, respectively. Conclusion: JK1201I exhibits promising efficacy and relatively low toxicities as a second‐line monotherapy for SCLC, warranting further large‐scale clinical studies to evaluate its efficacy in greater detail. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is one of the most aggressive malignant tumors of the brain. We queried PubMed for articles about molecular predictor markers in GBM. This scoping review aims to analyze the most important outcome predictors in patients with GBM and to compare these factors in terms of absolute months of survival benefit and percentages. Performing a gross total resection for patients with GBM undergoing optimal chemo- and radiotherapy provides a significant benefit in overall survival compared to those patients who received a subtotal or partial resection. However, compared to IDH-Wildtype GBMs, patients with IDH-Mutant 1/2 GBMs have an increased survival. MGMT promoter methylation status is another strong outcome predictor for patients with GBM. In the reviewed literature, patients with methylated MGMT promoter lived approximately 50% to 90% longer than those with an unmethylated MGMT gene promoter. Moreover, KPS is an important predictor of survival and quality of life, demonstrating that we should refrain from aggressive surgery in important brain areas. As new therapies (such as TTFs) emerge, we are optimistic that the overall median survival will increase, even for IDH-Wildtype GBMs. In conclusion, molecular profiles are stronger outcome predictors than the extent of neurosurgical resection for GBM. [ABSTRACT FROM AUTHOR]

Immune activation status determines non-small cell lung cancer (NSCLC) prognosis, with reported positive/negative associations for T helper type 2 (TH2) responses, including allergen-specific IgE and eosinophils. Our study seeks to explore the potential impact of these comorbid immune responses on the survival rates of patients with NSCLC. Our retrospective study used data from the Data Warehouse of the German Center for Lung Research (DZL) and Lung Biobank at Thoraxklinik Heidelberg. We estimated the association of blood eosinophilia and neutrophilia on survival rates in an inflammatory cohort of 3143 patients with NSCLC. We also tested sensitization to food and inhalants and high-sensitivity C-reactive protein (hs-CRP) in a comorbidity cohort of 212 patients with NSCLC. Finally, we estimated the infiltration of immune-relevant cells including eosinophils, T-cells, and mast cells in a tissue inflammatory sub-cohort of 60 patients with NSCLC. Sensitization to at least one food or inhalant (sIgE) was higher in patients with adenocarcinoma (adeno-LC) than the non-adenocarcinoma (non-adeno-LC). Furthermore, hs-CRP was higher in non-adeno-LC compared with adeno-LC. Peripheral inflammation, particularly eosinophilia and neutrophilia, was associated with poor survival outcomes in NSCLC with a clear difference between histological subgroups. Finally, blood eosinophilia was paralleled by significant eosinophil infiltration into the peritumoral tissue in the lung. This study provides novel perspectives on the crucial role of peripheral inflammation, featuring eosinophilia and neutrophilia, with overall survival, underscoring distinctions between NSCLC subgroups (adeno-LC vs. non-adeno-LC). Peripheral eosinophilia enhances eosinophil infiltration into tumors. This sheds light on the complex interplay between inflammation, eosinophil infiltration, and NSCLC prognosis among various histological subtypes. Further studies are required to underscore the role of eosinophils in NSCLC among different histological subgroups and their role in shaping the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Background: Although survival outcomes for neuroendocrine liver metastases (NETLM) are improved with liver-direct therapies (LDT), including hepatic debulking and nonsurgical trans-arterial embolization, the benefit is less established in the setting of concurrent extrahepatic disease (EHD). We performed a population-based study to characterize the rates of LDT being performed for NETLM with EHD patients and whether LDT is associated with survival outcomes. Methods: Patients with NETLM and EHD were identified using the California Cancer Registry database merged with data from the California Office of Statewide Health Planning and Development between 2000 and 2012. Demographics, clinical characteristics, and survival outcomes were analyzed for these patients with and without LDT. Results: 327 NETLM patients with EHD were identified. EHD sites included lung, peritoneum, bone, and brain. A total of 71 (22%) of these patients underwent LDT. Compared to NETLM with EHD patients who did not undergo LDT, patients who received LDT had longer median overall survival (27 vs. 16 months, p = 0.006). Within the LDT group, 23 patients underwent liver resection. Liver resection was associated with longer median overall survival compared to nonsurgical LDT (138 vs. 13 months, p < 0.001). Conclusions: LDT candidacy should be determined for patients on a case-by-case basis, but the presence of EHD should not preclude LDT with appropriate patient selection. [ABSTRACT FROM AUTHOR]

Simple Summary: This study focuses on Stage IIIA-N2 non-small cell lung cancer (NSCLC), which occurs when lung cancer has spread to lymph nodes in the centre of the chest but not to distant parts of the body. This type of cancer is difficult to treat, and survival rates remain low despite advances in therapy. The research is based on real-world data from Guy's Thoracic Cancer Database and aims to enhance our understanding of patient outcomes and identify important factors that impact survival and disease progression. By examining various treatment strategies, the study aims to offer insights that could help tailor treatment approaches to individual patients. The findings underscore the need for personalised care and the potential benefits of incorporating newer therapeutic options, ultimately leading to better survival outcomes for patients with this challenging form of lung cancer. Background: Stage IIIA-N2 non-small cell lung cancer (NSCLC) poses a significant clinical challenge, with low survival rates despite advances in therapy. The lack of a standardised treatment approach complicates patient management. This study utilises real-world data from Guy's Thoracic Cancer Database to analyse patient outcomes, identify key predictors of overall survival (OS) and disease-free survival (DFS), and address the limitations of randomised controlled trials. Methods: This observational, single-centre, non-randomised study analysed 142 patients diagnosed with clinical and pathological T1/2 N2 NSCLC who received curative treatment from 2015 to 2021. Patients were categorised into three groups: Group A (30 patients) underwent surgery for clinical N2 disease, Group B (54 patients) had unsuspected N2 disease discovered during surgery, and Group C (58 patients) received radical chemoradiation or radiotherapy alone (CRT/RT) for clinical N2 disease. Data on demographics, treatment types, recurrence, and survival rates were analysed. Results: The median OS for the cohort was 31 months, with 2-year and 5-year OS rates of 60% and 30%, respectively. Group A had a median OS of 32 months, Group B 36 months, and Group C 25 months. The median DFS was 18 months overall, with Group A at 16 months, Group B at 22 months, and Group C at 17 months. Significant predictors of OS included ECOG performance status, lymphovascular invasion, and histology. No significant differences in OS were found between treatment groups (p = 0.99). Conclusions: This study highlights the complexity and diversity of Stage IIIA-N2 NSCLC, with no single superior treatment strategy identified. The findings underscore the necessity for personalised treatment approaches and multidisciplinary decision-making. Future research should focus on integrating newer therapeutic modalities and conducting multi-centre trials to refine treatment strategies. Collaboration and ongoing data collection are crucial for improving personalised treatment plans and survival outcomes for Stage IIIA-N2 NSCLC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Vulvar cancer is a rare cancer but has a high cure rate if diagnosed early and treated appropriately. In the early 20th century, 5-year survival rates were only 15–20% because of inadequate treatment of both the primary cancer and the groin lymph nodes. By the mid-20th century, 5-year survival rates rose to 60–70% with the introduction of the radical resection of the vulva, together with the radical resection of the groin and usually pelvic lymph nodes. Although cure rates were good, physical and psychological morbidity were high with this extensive surgery. Hence, various modifications have been proposed over the past 50 years to decrease this morbidity without compromising survival, including modifications to the extent of both the vulvectomy and lymph node dissection. This paper looks at the results these modifications have on both survival and morbidity. Vulvar cancer is a rare disease, and cure rates were low until the mid-20th century. The introduction of an en bloc radical vulvectomy and bilateral groin and pelvic lymph node dissection saw them rise from 15–20% to 60–70%. However, this very radical surgery was associated with high physical and psychological morbidity. Wounds were usually left open to granulate, and the average post-operative hospital stay was about 90 days. Many attempts have been made to decrease morbidity without compromising survival. Modifications that have proven to be successful are as follows: (i) the elimination of routine pelvic node dissection, (ii) the use of separate incisions for groin dissection, (iii) the use of unilateral groin dissection for lateral, unifocal lesions, (iv) and radical local excision with 1 cm surgical margins for unifocal lesions. Sentinel node biopsy with ultrasonic groin surveillance for patients with node-negative disease has been the most recent modification and is advocated for patients whose primary cancer is <4 cm in diameter. Controversy currently exists around the need for 1 cm surgical margins around all primary lesions and on the appropriate ultrasonic surveillance for patients with negative sentinel nodes. [ABSTRACT FROM AUTHOR]

Objectives: Head and neck cancers (HNCs) represent a significant global health concern due to high morbidity and mortality rates. Despite therapeutic advances, the prognosis for advanced or recurrent cases remains challenging. Nivolumab obtained approval for recurrent or metastatic HNC based on the Phase III CheckMate 141 trial. This study aimed to evaluate the real-world outcomes of nivolumab in patients with non-nasopharyngeal HNC. Design: In this multicenter retrospective study, we analyzed 124 patients with recurrent or metastatic non-nasopharyngeal HNC who received nivolumab in the second-line setting and beyond. Data were collected from 20 different cancer centers across Turkey. The effectiveness and safety of the treatment and survival outcomes were evaluated. Results: Nivolumab exhibited favorable clinical responses, yielding an objective response rate of 29.9% and a disease control rate of 55.7%. Safety assessments revealed a generally well-tolerated profile, with no instances of treatment discontinuation or mortality due to side effects. Survival analysis disclosed a median overall survival (OS) of 11.8 (95% CI 8.4–15.2) months. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 1.64, p = 0.045), laryngeal location (HR: 0.531, p = 0.024), and neutrophil-to-lymphocyte ratio > 3.5 (HR: 1.97, p = 0.007) were independent predictors of OS. Conclusions: Nivolumab is an effective and safe treatment option for patients with recurrent or metastatic non-nasopharyngeal HNC in real-world settings. Further studies are needed on factors affecting response to treatment and survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Advancements in nasopharyngeal carcinoma (NPC) treatment have led to a focus on personalized treatment. Circulating tumor cells (CTCs) are important for liquid biopsies and personalized treatment but are not being fully utilized. This study examined how pre- and post-treatment CTC counts, EMT subtypes, clinical characteristics, and patient prognosis are related in order to support the use of liquid biopsy in managing NPC. Methods: This retrospective study included 141 patients with locally advanced NPC. All patients underwent CanPatrol™ CTC detection pre- and post-treatment and were categorized into EMT subtypes: epithelial type, mixed type, and mesenchymal type. This study analyzed CTC enumeration, EMT subtypes, and their associations with clinical characteristics and survival outcomes. Results: The results indicated a positive correlation between the pre-treatment detection rate of CTCs and N stage (P < 0.01), alongside a positive correlation with the TNM clinical stage (P = 0.02). Additionally, the detection rate of mesenchymal CTCs post-treatment is positively associated with the N stage (P = 0.02). The enumeration of CTCs pre- and post-treatment is negatively correlated with prognosis and has statistical significance. Additionally, an investigation into the EMT subtypes of CTCs revealed a significant association between the presence of mesenchymal CTCs pre- and post-treatment and decreased overall survival (OS) (P < 0.05). Furthermore, T stage, N stage, TNM clinical stage, and Epstein-Barr virus (EBV) DNA were also significantly correlated with OS. Conclusion: The study found that mesenchymal CTCs pre- and post-treatment, as well as the number of CTCs, were linked to a poor prognosis. [ABSTRACT FROM AUTHOR]

Introduction and Objective: Kidney-sparing surgery (KSS) for upper tract urothelial cancer (UTUC) has gained increasing interest recently. However, there is limited contemporary data regarding the role of KSS in ureteral urothelial carcinoma. Therefore, we investigated the survival outcomes of ureteral urothelial carcinoma after KSS from a large, prospective international UTUC registry. Methods: The Clinical Research Office of the Endourology Society-Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry included patients with UTUC who received KSS or radical nephroureterectomy (RNU) between 2014 and 2019. In this study, we included patients with ureteral UTUC only. Study outcomes included overall survival (OS), cancer-specific survival (CSS), upper tract recurrence-free survival (RFS), intravesical RFS, progression-free survival (PFS), and metastasis-free survival (MFS). Propensity score matching (PSM) was performed to balance the tumor features' differences between groups. Results: Of the 391 patients with ureteral UTUC, 309 (79.0%) received RNU and 82 (21.0%) received KSS by ureteroscopy with laser ablation (n = 28) or segmental resection (n = 54). After PSM, there were no differences in OS (p = 0.525), CSS (p = 0.487), upper tract RFS (p = 0.147), intravesical RFS (p = 0.989), PFS (p = 0.617), and MFS (p = 0.336) between KSS and RNU. There were no significant differences between ureteroscopic ablation and segmental resection in OS, CSS, intravesical RFS, PFS, and MFS with RNU. Proximal ureteral UTUC had worse OS and CSS outcomes than other tumor locations following segmental resection. Conclusions: In patients with ureteral UTUC, no significant differences in long-term survival outcomes were observed between KSS and RNU. Proximal ureteral UTUC had worse survival outcomes over other tumor locations following segmental resection. [ABSTRACT FROM AUTHOR]

Objective: To synthesize contemporary evidence of the impact of contralateral prophylactic mastectomy (CPM) on survival outcomes in patients with unilateral breast cancer (UBC). Methods: PubMed, EMBASE and Scopus databases were searched for observational studies published up to November 15, 2023. Random-effects model was used to obtain pooled effect estimates that were reported as hazards ratio (HR) with 95% confidence intervals (CI). The outcomes of interest were overall survival (OS), breast cancer-specific survival (BCSS), recurrence free survival (RFS) and risk of contralateral breast cancer (CBC). Results: Twenty-one studies were included. Most studies had a retrospective design. CPM was associated with significant improvement of OS (HR 0.80, 95% CI: 0.75, 0.85), BCCS (HR 0.82, 95% CI: 0.74, 0.90), and RFS (HR 0.72, 95% CI: 0.60, 0.86) and significantly reduced risk of CBC (HR 0.05, 95% CI: 0.03, 0.09) in patients with UBC. No evidence of publication bias was detected. Conclusion: Our results provide strong evidence supporting the positive impact of CPM on survival outcomes in patients with UBC. Further research and long-term follow-up studies are warranted to validate these findings. [ABSTRACT FROM AUTHOR]

Background To evaluate the midterm follow-up and 5-year survival outcome of the minimally invasive direct coronary artery bypass (MIDCAB) procedure compared with the survival of the general Swiss population. Methods Retrospective study on preoperative data, intraoperative data, and postoperative outcome of patients who underwent MIDCAB surgery between June 2010 and February 2019. To assess validity of this surgical therapy, outcomes were compared with survival data of a gender- and age-matched cohort of the general Swiss population taken from the database of the Swiss Federal Statistical Office. Results A total of 88 patients were included. Median (interquartile range [IQR[) age was 66 (56–75) years, and 27% (n = 24) were female. The median (IQR) length of the in-hospital stay was 7 (6–8) days. No postoperative stroke occurred. The 30-day mortality was 1.1% (n = 1). Reintervention for failed left internal mammary artery was needed in 1.1% (n = 1). The median (IQR) ejection fraction was 58% (47–60) preoperatively and remained stable during follow-up. The median (IQR) follow-up period was 3 (1.1–5.2) years. Five years postoperatively, 83% (confidence interval, 69–91) of the patients were alive, showing an overlap with the range of survival of the matched subcohort of the general Swiss population (range, 84–100%). Conclusion Though suffering from coronary heart disease, patients after MIDCAB show almost equal survival rates as an equivalent subcohort corresponding to the general Swiss population matched on age and gender. Thus, our data show this treatment to be safe and beneficial. [ABSTRACT FROM AUTHOR]

Objectives: To determine the effects of prophylactic urethrectomy (PU) on oncological and perioperative outcomes in patients with bladder cancer (BC) undergoing radical cystectomy (RC). Methods: This retrospective study analyzed data on 1976 evaluable patients with BC who underwent RC. Patients were drawn from 36 institutions within the Japanese Urological Oncology Group. Oncological outcomes were compared using restricted mean survival times (RMSTs) based on inverse probability of treatment weighting (IPTW)‐adjusted Kaplan–Meier curves for non‐urinary tract recurrence‐free survival (NUTRFS), cancer‐specific survival (CSS), and overall survival (OS). Interaction terms within IPTW‐adjusted Cox regression models were examined to assess the heterogeneity of treatment effect based on the risk of urethral recurrence (UR). The association between PU, estimated blood loss (EBL), and the incidence of severe postoperative surgical complications (SPSCs) (Clavien‐Dindo grade 3 or higher) was analyzed. Results: Of 1976 patients, 1448 (73.3%) received PU. IPTW adjustment was used to balance baseline characteristics between the treatment groups. Within the 107‐month window of patient monitoring, PU showed no survival benefits (NUTRFS difference: 0.2 months [95% confidence interval: −6.8 to 7.3]; CSS, 1.2 [−4.9 to 7.3]; OS, 0 [−6.5 to 6.5]). No significant interactions were observed with factors associated with UR, and PU was associated with unfavorable perioperative outcomes (EBL, 1179 mL vs. 983 mL; SPSC, 14.6% vs. 7.0%). Conclusions: This study showed that (1) PU was not associated with survival in patients with BC undergoing RC, regardless of UR‐associated factors, and (2) PU was associated with unfavorable perioperative outcomes. [ABSTRACT FROM AUTHOR]

Craniopharyngiomas (CPs) are rare tumors of the sellar region often leading to significant comorbidities due to their close proximity to critical structures. The aim of this study was to analyze survival outcome and late toxicities after surgery and proton beam therapy (PBT) in childhood CPs. Within the prospective registry study "KiProReg" (DRKS0000536), data of 74 childhood patients with CP, receiving PBT between August 2013 to June 2022 were eligible. Late toxicities were analyzed according to the grading system of the Common Terminology Criteria for Adverse Events, version 4.0. Median follow-up since first diagnosis was 4.3 years (range, 0.8-14.7). In addition, 75.7% of patients received PBT at time of disease progression or recurrence, whereas 24.3% as part of their primary therapy (definitive or adjuvant). Predominantly (85.1%), pencil beam scanning technique was used. The median total dose and initial tumor volume were 5400 cGy relative biologic effectiveness (RBE) and 17.64 cm³ (range, 3.07-300.59), respectively. The estimated (±SE) 3-year overall survival, progression-free, and cystic failure-free survival rate after PBT were 98.2% (±1.7), 94.7% (±3.0), and 76.8% (±5.4), respectively. All local failures (n = 3) were in-field relapses necessitating intervention and occurred exclusively in patients receiving PBT at progression or recurrence. Early cystic enlargements after PBT were typically asymptomatic and self-limiting. Fatigue, headaches, vision disorders, obesity, and endocrinopathies were the predominant late toxicities. No high-grade (≥3) new-onset visual impairment or cognitive deterioration occurred compared with baseline. The presence of cognitive impairments at the end of follow-up correlated with size of the planning target volume (P =.034), D mean dose to the temporal lobes (P =.032, P =.045) and the number of surgical interventions before PBT (P =.029). Our findings demonstrate favorable local control rates using modern PBT with acceptable late toxicities. Cyst growth within 12 months after radiation therapy is typically not associated with tumor progression. Longer follow-up must be awaited to confirm results. [ABSTRACT FROM AUTHOR]

Background: Despite early diagnosis and medical interventions, patients with methylmalonic acidemia (MMA) suffer from multi‐organ damage and recurrent metabolic decompensations. Methods: We conducted the largest retrospective multi‐center cohort study so far, involving five transplant centers (NCCHD, KUH, KUHP, ATAK, and EMC), and identified all MMA patients (n = 38) undergoing LDLT in the past two decades. Our primary outcome was patient survival, and secondary outcomes included death‐censored graft survival and posttransplant complications. Results: The overall 10‐year patient survival and death‐censored graft survival rates were 92% and 97%, respectively. Patients who underwent LDLT within 2 years of MMA onset showed significantly higher 10‐year patient survival compared to those with an interval more than 2 years (100% vs. 81%, p = 0.038), although the death‐censored graft survival were not statistically different (100% vs. 93%, p = 0.22). Over the long‐term follow‐up, 14 patients (37%) experienced intellectual disability, while two patients developed neurological complications, three patients experienced renal dysfunction, and one patient had biliary anastomotic stricture. The MMA level significantly decreased from 2218.5 mmol/L preoperative to 307.5 mmol/L postoperative (p = 0.038). Conclusions: LDLT achieves favorable long‐term patient and graft survival outcomes for MMA patients. While not resulting in complete cure, our findings support the consideration of early LDLT within 2 years of disease onset. This approach holds the potential to mitigate recurrent metabolic decompensations, and preserve the long‐term renal function. [ABSTRACT FROM AUTHOR]

Objective: We aim to report the epidemiology, surgical outcomes, and survival rates of pediatric patients with posterior fossa tumors in a large single-center case series. Methods: A retrospective analysis was conducted on pediatric patients who underwent surgical treatment for posterior fossa tumors between January 2011 and January 2019. Results: A total of 135 pediatric patients, with an average age of 7.5 years at diagnosis and a mean follow-up of 35.7 months, were included in the study. Most tumors were located within the midline, with ventriculomegaly observed in 71.4% of the patients. Pilocytic astrocytomas encompassed the majority of tumors (34.1%), followed by medulloblastomas (27.4%) and ependymomas (11.8%). Gross total resection (GTR) was achieved in 71.8% of the patients, with a recurrence rate of 20%. Surgical complications were observed in 25.9% of the patients. GTR significantly impacted 5-year overall survival (OS) and 4-year progression-free survival (PFS) in patients with posterior fossa tumors. Patients who underwent GTR had a 5-year OS of 89.7%, compared to 72.7% for near-total resection and 70.8% for subtotal resection. The 4-year PFS for patients who underwent GTR was 82.5%, whereas it was 63.6% for patients who underwent near-total resection and 54.2% for patients who underwent subtotal resection. Conclusion: Surgical resection remains the main treatment for pediatric posterior fossa tumors, and higher resection rates are linked to better survival outcomes. Despite limited resources for molecular diagnosis, our institution has demonstrated that a specialized neurooncological center with a high surgical volume can still achieve favorable survival outcomes for these patients. [ABSTRACT FROM AUTHOR]

Background & Aims: Intrahepatic cholangiocarcinoma (iCCA) has two main histological subtypes: large and small duct‐type iCCA, which are characterized by different clinicopathological features. This study was conducted with the purpose of expanding our understanding of their differences in molecular features and immune microenvironment. Methods: We selected 132 patients who underwent radical surgery at our department between 2015 and 2021 for clinical and survival analyses. Whole‐exome sequencing was performed to analyse mutational landscapes. Bulk RNA sequencing and single‐cell RNA sequencing data were used for pathway enrichment and immune infiltration analyses based on differentially expressed genes. The function of PPP1R1B was analysed both in vitro and in vivo and the gene mechanism was further investigated. Results: We found that large duct‐type iCCA had worse overall survival and recurrence‐free survival rates than small duct‐type iCCA. Mutations in ARID1A, DOT1L and ELF3 usually occur in large duct‐type iCCA, whereas mutations in IDH1 and BAP1 occur in small duct‐type iCCA. Among the differentially expressed genes, we found that PPP1R1B was highly expressed in large duct‐type iCCA tumour tissues. Expression of PPP1R1B promoted cell proliferation, migration and invasion and indicated a worse prognosis. A combination of USF2 with the promoter of PPP1R1B can enhance gene expression in iCCA, which may further affect the expression of genes such as AHNAK, C4BPA and activating the PI3K/AKT pathway. Conclusions: Our findings extend our understanding of large and small duct‐type iCCA. In addition, PPP1R1B may serve as a potential marker and therapeutic target for large duct‐type iCCA. [ABSTRACT FROM AUTHOR]