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Primary paragangliomas (PGs) are extra-adrenal neuroendocrine tumours that are extremely rare. Multiple lesions in the central nervous system raise suspicion of a metastatic process. Lack of consensus on their management warrants the categorization of existing literature to evaluate management options. A systematic review of the medical literature on paraganglioma within the cranial vault was completed in accordance with PRISMA guidelines using the Medline database. Tumour physical measures, management parameters, and immunohistochemistry of all documented cases of primary and secondary paraganglioma within the cranial vault were descriptively compared. This review was augmented by comparison with our centre's case of a 48-year-old man diagnosed with metastatic PG originating in the cauda equina and seeding in the cerebellum. Histological parameters within the literature was also established. The systematic literature review yielded published 52 papers. Most prevalent primary intracranial PGs (n = 37) were in the sellar region (78%, n = 23) and the cerebellum (21%, n = 6). The highest progression free survival was seen in primary sellar PGs (87.5% by 34.5 months) and cerebellar PGs (100% by 35.7 months) when treated with adjuvant radiotherapy with subtotal resection or gross total resection, respectively. Contrasting, the most frequent intracranial PGs metastases (n = 15) occurred in the cerebellum (36%, n = 6), and the cerebral parenchyma (29%, n = 4). Their recurrence rate was between 4 and 10% and these metastasized PG in the cerebellum are slow growing (8.9 years, range: 3–22 years). Adjuvant radiotherapy with Gross Total Resection resulted in the optimum progression-free survival (100% up to 48 months) for the patient with PGs metastasis to the cerebellum. Metastatic PGs tend to be slow-growing and are clinically silent tumours. Diagnosed patients should undergo regular surveillance neuroradiological assessment, regardless of symptomatology, for metastases along the complete neural axis. We recommend operative management with GTR and adjunct RT in these patients. [ABSTRACT FROM AUTHOR]

Sequential, multiple assignment, randomized trial (SMART) designs are appropriate for comparing adaptive treatment interventions, in which intermediate outcomes (called tailoring variables) guide subsequent treatment decisions for individual patients. Within a SMART design, patients may be re-randomized to subsequent treatments following the outcomes of their intermediate assessments. In this paper, we provide an overview of statistical considerations necessary to design and implement a two-stage SMART design with a binary tailoring variable and a survival final endpoint. A chronic lymphocytic leukemia trial with a final endpoint of progression-free survival is used as an example for the simulations to assess how design parameters, including, choice of randomization ratios for each stage of randomization, and response rates of the tailoring variable affect the statistical power. We assess the choice of weights from restricted re-randomization on data analyses and appropriate hazard rate assumptions. Specifically, for a given first-stage therapy and prior to the tailoring variable assessment, we assume equal hazard rates for all patients randomized to a treatment arm. After the tailoring variable assessment, individual hazard rates are assumed for each intervention path. Simulation studies demonstrate that the response rate of the binary tailoring variable impacts power as it directly impacts the distribution of patients. We also confirm that when the first stage randomization is 1:1, it is not necessary to consider the first stage randomization ratio when applying the weights. We provide an R-shiny application for obtaining power for a given sample size for SMART designs. [ABSTRACT FROM AUTHOR]

To identify the prognostic value of the pretreatment geriatric nutritional risk index (GNRI) in colorectal cancer. Several electronic databases were searched up to March 15, 2022, for relevant studies. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), respectively. The hazard ratios (HRs) with 95% confidence intervals (CIs) were combined. Bess's funnel plot and Egger's test were conducted to detect publication bias, and the trim-and-fill method was performed to identify potentially unpublished papers and their impacts on the overall results. Nine studies from Japan and China involving 3440 participants were enrolled in the current meta-analysis. The pooled results indicated that a low pretreatment GNRI was significantly associated with poorer OS (HR = 2.28, 95% CI: 1.69–3.07, P < 0.001; I2=63.5%, Pheterogeneity=0.005) and DFS (HR = 1.62, 95% CI: 1.35–1.96, P < 0.001; I2=46.4%, Pheterogeneity=0.114). Subgroup analysis stratified by country and treatment showed similar results. Significant publication bias was manifested by the asymmetric Begg's funnel plot and P = 0.012 of Egger's test, but three potentially unpublished studies did not have a significant impact on the overall results. A lower pretreatment GNRI was a novel prognostic risk factor for Japanese and Chinese colorectal cancer patients. [ABSTRACT FROM AUTHOR]

This paper presents statistical evidence of roadside vegetation's contribution to pavement roughness progression rates. Detailed statistical and regression analysis of the roadside vegetation data collected via satellite imageries and road roughness data collected via high speed road profiler was performed. Elaborative investigation on interaction between roadside vegetation and waveband roughness progression has provided a clear indication of tree variable's contribution on road deterioration. Statistical parameters such as moderate Pearson correlation coefficient (r) values, low mean squared error (MSE), root mean squared error (RMSE), mean absolute error (MAE) values, high Willmott's index of agreement (d) were obtained for training and validation datasets, that depicted the potentiality of tree variables as predictors in pavement roughness progression rate modelling. Statistical evidence showed that effect of trees on road deterioration was more noticeable on long wavelength roughness progression rates. This can be justified via prevailing soil moisture interaction in expansive soil deposits subjected to moisture withdrawal of deciduous trees in arid climate conditions. Overall, the findings of this paper exemplify on the necessity of considering the presence of roadside vegetation in road deterioration analysis, and suggesting the scope of improvement for prediction performance. [ABSTRACT FROM AUTHOR]

Interval-censored data arise frequently in medical studies of diseases that require periodic examinations for symptoms of interest, such as disease-free survival (DFS). This paper provides an introduction to the R package ICBayes which implements a set of programs for analyzing case 1 interval-censored data and case 2 interval-censored data under Bayesian semiparametric framework. The main function ICBayes fits commonly-used survival regression models: proportional hazards, proportional odds, and probit. A simulation study is conducted to compare the performance of the package with two R packages that fit Bayesian proportional hazards, proportional odds, and accelerated failure time models. The use of the package is illustrated through analyzing a case 2 interval-censored breast cosmesis data and a case 1 interval-censored animal tumorigenicity data. [ABSTRACT FROM AUTHOR]

This paper is concerned with the robust feature screening method for ultra-high dimensional right censored data. A new robust and model-free feature screening approach is built upon a screening index constructed from a fresh measure of dependence between the survival time and a single covariate. One attractive property of this newly introduced index is that it equals zero if the survival time and covariate are independent. In addition, it is invariant to monotonic transformation of the response, and robust against heavy-tailed distributions and outliers for the response. These appealing properties render the derived feature screening approach to be a competitive one among feature screening methods for ultra-high dimensional right censored data. We establish the sure screening property for the suggested feature screening procedure under some regularity conditions, and evaluate its performance through numerical studies. Numerical comparisons with several main competitors show the advantages of the newly proposed means over its main competitors. The well-known diffuse large-B-cell lymphoma (DLBCL) data is utilized to illustrate our methodology. [ABSTRACT FROM AUTHOR]

This paper evaluates the efficacy and safety of repeat hepatic resection and radiofrequency ablation in the treatment of recurrent hepatocellular carcinoma We retrieved and collected all relevant articles from the inception to 8 March 2020. After data extraction, we conducted meta-analysis and carried out the heterogeneity test, sensitivity analysis, and publication bias test to evaluate reliability A total of 12 studies with 1746 patients (rHR 837, RFA 909) were included. rHR was similar to RFA in a one-year overall survival rate (OS), while rHR was superior to RFA in 3- and 5-year OS and 1-, 3-, and 5-year disease-free survival rates (DFS), but the procedure-related complications of RFA were significantly less than those of rHR. Among the subgroups with Milan criteria, rHR was similar to RFA in 1-, 3-, and 5-year OS and 1-year DFS, but superior to RFA in 3- and 5-year DFS. RFA is the first choice for recurrent HCC meeting Milan criteria. When it does not meet the Milan criteria, minimally invasive treatment should not be carried out at the cost of survival, and rHR should be the first choice. [ABSTRACT FROM AUTHOR]

Systemic immune-inflammation index (SII) has been reported in numerous studies to effectively predict the survival outcomes of urinary system cancers; however no agreement has been reached. This meta-analysis aimed to explore the prognostic significance of pre-treatment SII in tumours of the urinary system. Relevant published articles were selected from Web of Science, PubMed, Embase, and the Cochrane Library up to 30 August 2020. The hazard ratios (HRs) with 95% confidence intervals (CIs) were computed to estimate the associations of pre-treatment SII with overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS) in urinary system cancers. 13 papers were included in our meta-analysis. From the combined data, we found that a high pre-treatment SII indicated a markedly worse OS (HR = 1.98; 95% CI: 1.75–2.23; p <.001), PFS (HR: 2.08; 95% CI: 1.32–3.26; p =.002), and CSS (HR: 2.41, 95% CI: 1.73–3.35, p <.001). Additionally, patients with an elevated SII value might have undesirable pathological characteristics, including a large tumour size, a poor differentiation grade, and an advanced tumour stage (all p <.001). Pre-treatment SII could be used as a non-invasive and promising biomarker to indicate the prognosis of urinary system cancer patients. This meta-analysis evaluates the predictive value of systemic immune-inflammation index (SII) for patients with urinary system cancer. A high pre-treatment SII indicates a poor prognosis. SII can serve as a promising non-invasive biomarker to help clinicians assess the prognosis and develop treatment strategies for urinary system cancer patients. [ABSTRACT FROM AUTHOR]

Medical advances including the neoadjuvant anti-PD-1 immunotherapy play a role in promoting clinical outcomes such as improved overall and progression-free survival probabilities. This paper considers the regression analysis of current status data with a cured subgroup in the population using a semiparametric non-mixture cure model. We propose a sieve maximum likelihood estimation for the model with the Bernstein polynomials. Moreover, an expectation–maximization (EM) algorithm is developed under the non-mixture cure model to calculate the estimators for both parametric and non-parametric components. Under some mild conditions, the asymptotic properties of the estimators are established, including the strong consistency, the convergence rate and the asymptotic normality. Simulation studies are conducted to investigate the finite sample performance of the proposed estimators. A real dataset from the tumorigenicity experiment is analysed for illustration. [ABSTRACT FROM AUTHOR]

Objectives: Cancer cells undergo metabolic reprogramming to adapt to high oxidative stress, but little is known about how metabolic remodeling enables gastric cancer cells to survive stress associated with aberrant reactive oxygen species (ROS) production. Here, we aimed to identify the key metabolic enzymes that protect gastric cancer (GC) cells from oxidative stress. Methods: ROS level was detected by DCFH-DA probes. Multiple cell biological studies were performed to identify the underlying mechanisms. Furthermore, cell-based xenograft and patient-derived xenograft (PDX) model were performed to evaluate the role of MTHFD2 in vivo. Results: We found that overexpression of MTHFD2, but not MTHFD1, is associated with reduced overall and disease-free survival in gastric cancer. In addition, MTHFD2 knockdown reduces the cellular NADPH/NADP+ ratio, colony formation and mitochondrial function, increases cellular ROS and cleaved PARP levels and induces in cell death under hypoxia, a hallmark of solid cancers and a common inducer of oxidative stress. Moreover, genetic or pharmacological inhibition of MTHFD2 reduces tumor burden in both tumor cell lines and patient-derived xenograft-based models. Discussion: our study highlights the crucial role of MTHFD2 in redox regulation and tumor progression, demonstrating the therapeutic potential of targeting MTHFD2. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis seeks to assess the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. Methods: Databases from PubMed, Embase, and the Cochrane Library were all thoroughly searched for pertinent research. Outcomes include complete response (CR), partial response (PR), stable disease (SD), disease progression (PD), overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and adverse events (AEs) were retrieved for further analysis. Results: Ten trials with 721 patients were included in this meta-analysis. The pooled results for patients with cervical cancer receiving pembrolizumab were as follows: CR (0.06, 95%CI: 0.02–0.10), PR (0.15, 95%CI: 0.08–0.22), SD (0.16, 95%CI: 0.13–0.20), PD (0.50, 95%CI: 0.25–0.75), ORR (0.26, 95%CI: 0.11–0.41) and DCR (0.42, 95%CI: 0.13–0.71), respectively. Regarding survival analysis, the pooled mPFS and mOS were 3.81 and 10.15 months. Subgroup analysis showed that pembrolizumab in combination was more beneficial in CR (0.16 vs. 0.03, p = 0.012), PR (0.24 vs. 0.08, p = 0.032), SD (0.11 vs. 0.19, p = 0.043), ORR (0.42 vs. 0.11, p = 0.014), and mPFS (5.54 months vs. 2.27 months, p < 0.001) than as single agent. The three most common AEs were diarrhoea (0.25), anaemia (0.25), and nausea (0.21), and the incidence of grade 3–5 AEs was significantly lower, rarely surpassing 0.10. Conclusions: For patients with advanced or recurrent cervical cancer, this systematic review and meta-analysis demonstrated that pembrolizumab had a favourable efficacy and tolerability. Future research will primarily focus on optimising customised regiments that optimally integrate pembrolizumab into new therapies and combination strategies. Designed to maximise patient benefit and efficiently control adverse effects while maintaining a high standard of living. PLAIN LANGUAGE SUMMARY: This study demonstrated the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. The study found that an upfront combination of chemotherapy and pembrolizumab immunotherapy appears to be a compelling strategy for these patients. More large-scale and multicentre randomised controlled trials will be required in the future to validate the precise benefits of pembrolizumab in new therapies and combination strategies for the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

Findings regarding the relationship between sarcopenia and lymphoma have been inconsistent across studies. This study investigated the association between sarcopenia and lymphoma. We systematically searched the Embase, Science Direct, Cochrane Library, and PubMed databases from inception to 31 March 2024 to identify relevant studies. Two researchers independently extracted and evaluated studies that met inclusion and exclusion criteria. Twenty-six studies with 3659 participants were included. Sarcopenic lymphoma patients had poor overall survival (OS) (HR = 1.88; 95% CI: 1.47–2.41; p < 0.001). The heterogeneity was high (I2=80%). However, the result of the Egger test indicated a significant publication bias (p < 0.001). After employing the trim and fill method to adjust for this bias, the HR of OS became non-significant (p > 0.05). The progression-free survival (PFS) was worse in sarcopenic patients (HR = 1.77; 95% CI: 1.37–2.29; p < 0.001; I2=70%). There was no significant publication bias (p > 0.05). In the subgroup analyses, sarcopenia was a negative predictor of OS in lymphoma patients who undergo hematopoietic cell transplantation (HCT) (HR = 1.61;95% CI: 1.19–2.18; I2=30%). Male lymphoma patients with sarcopenia had a significantly worse OS (HR = 2.29; 95% CI:1.24–4.24; p = 0.009). Among patients with primary central nervous system lymphoma (PCNSL), those with sarcopenia defined by temporal muscle thickness (TMT) exhibited significantly worse OS (HR = 2.20; 95% CI:1.04–4.65; p = 0.039; I2=68%). Sarcopenia is associated with worse PFS in lymphoma patients. Subgroup analyses indicate that sarcopenia is a negative predictor of OS after HCT, and male lymphoma patients who suffer from sarcopenia have higher mortality. Sarcopenia defined by TMT is also a negative predictor of OS for patients with PCNSL. [ABSTRACT FROM AUTHOR]

Introduction: Despite major advances in the therapeutic management of multiple myeloma (MM), it remains an incurable disease. Several combinations of monoclonal antibodies with novel agents are being investigated with promising results in order to prolong progression-free and overall survival.Areas covered: This paper aims to critically present available data from clinical trials investigating the combination of elotuzumab with pomalidomide and dexamethasone in refractory/relapsed MM patients and determine its current role in clinical practice.Expert opinion: Pomalidomide-based combinations with monoclonal antibodies have been shown to be effective in patients with MM who are refractory to or have relapsed following treatment with lenalidomide and/or a proteasome inhibitor (PI). These regimens seem to be more effective than the standard combination of pomalidomide with dexamethasone alone. Taking into consideration that the vast majority of MM patients will receive upfront treatment including a PI and lenalidomide in the near future, pomalidomide-based triplets, such as elotuzumab-pomalidomide-dexamethasone, will become the standard of care in the second line of therapy. [ABSTRACT FROM AUTHOR]

Tyrosine kinase inhibitors (TKI) are gaining more ground in oncology, they are widely used in the treatment of multiple types of cancers; still important side effects limit their efficacy. The aim of this study is to evaluate the existing medical literature on TKI induced thyroid dysfunction, to assess the adverse effects of targeted therapy on thyroid function in oncological patients and to evaluate the effects of thyroid dysfunction on disease prognosis. We included in this review 22 original studies published between 2010 and 2019. We used the PubMed database to search for articles upon the development of hypothyroidism and hyperthyroidism in TKI treated patients. After a careful review of the existing literature, we selected the relevant studies and cross-referenced the bibliography of each paper. A number of 1641 patients were included in our review. We found that thyroid dysfunction is not a rare side effect of TKI treatment, approximately 33% of the total number of patients presented clinical hypothyroidism. We also studied the necessity of thyroid hormone substitution treatment, a quarter of evaluated patients needed substitution therapy. Multiple studies showed that there is a link between a patient developing hypothyroidism and progression free survival. Hypothyroidism is a frequent side effect of TKI treatment, which affects the quality of life, sometimes even determines physicians to stop TKI treatment altogether. Our study underlines the necessity of TSH baseline testing and monitoring in patients treated with TKI agents. [ABSTRACT FROM AUTHOR]

In this paper, we study the survival times of alternately occurring events. The dependence between the times to the two events is modelled through the Archimedean copula, while the dependence over the recurring cycles is modelled through a functional relationship of the distribution parameters. Taking account of appropriate censoring that may be present in the data, the model parameters are estimated using the maximum likelihood method. The standard errors of the estimators are then derived and confidence belts for the survival functions constructed. Methods for choosing the appropriate copula are also discussed. The results are illustrated through a clinical trial data on patients suffering from cystic fibrosis. A simulation study is also done to corroborate the results. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma (HL) involving the Waldeyer's ring (WR) and other extranodal head and neck sites are rare. We report our experience and PubMed literature review. Retrospective single institution cohort study using lymphoma data base and PubMed literature search using twenty-six various search terms. Twenty-nine patients were treated in our institution (1975–2018). Male:Female 22:7, median age at diagnosis 33 years (15–64), stages I–II:III–IV 25:4. Sites were nasopharynx (10), tonsil (9), parotid (5), mandible (2) and others (3). 20/29 patients received radiation therapy, 22/29 received chemotherapy. Ten years overall-survival and progression-free survival are 92% and 66% respectively. PubMed search showed 8766 citations and identified 357 patients including our patients. Male:Female 199:131, median age 45 years (5-89). Stages I–II in 286 (80%). Involvement was nasopharynx 109 (30.5%), tonsil 67 (18.8%), parotid 58 (16.2%), thyroid 45 (12.6%), adenoid 10 (2.8%), mandible 10 (2.8%) and others in 58 (16.2%). Pathology: mixed cellularity 99 (27.7%), nodular sclerosis 88 (24.6%), nodular lymphocyte-predominant 56 (15.7%), lymphocyte rich 25 (7%), classical-HL-not otherwise specified 16 (4.5%) and lymphocyte depleted 7 (2%) patients. Treatment details are available for 233 patients; 165 (46%) received radiation therapy, 137 (38%) chemotherapy. Complete remission in 208 (58%), progressive disease 14 (4%), no information 135 (38%). Overall, treatment failure in 54 (15%). Thirty (8.4%) have died; 21 disease related. KM overall-survival at 5 and 10 years was 88.5% and 77.6% respectively. This largest report showed that HL involving extranodal head and neck sites is not very uncommon and has excellent prognosis. [ABSTRACT FROM AUTHOR]

Surgery is a curative treatment option for many patients with malignant tumors. Increased attention has focused on the combination of surgery with chemotherapy, as multimodality treatment has been associated with promising results in certain cancer types. Despite these data, there remains clinical equipoise on optimal timing and patient selection for neoadjuvant or adjuvant strategies. Radiomics, an emerging field involving the extraction of advanced features from radiographic images, has the potential to revolutionize oncologic treatment and contribute to the advance of personalized therapy by helping predict tumor behavior and response to therapy. This review analyzes and summarizes studies that use radiomics with machine learning in patients who have received neoadjuvant and/or adjuvant chemotherapy to predict prognosis, recurrence, survival, and therapeutic response for various cancer types. While studies in both neoadjuvant and adjuvant settings demonstrate above average performance on ability to predict progression-free and overall survival, there remain many challenges and limitations to widespread implementation of this technology. The lack of standardization of common practices to analyze radiomics, limited data sharing, and absence of auto-segmentation have hindered the inclusion and rapid adoption of radiomics in prospective, clinical studies. [ABSTRACT FROM AUTHOR]

Laser interstitial thermal therapy (LITT) is a minimally invasive treatment method in managing primary brain neoplasms, brain metastases, radiation necrosis, and epileptogenic lesions, many of which are located in operative corridors that would be difficult to address. Although the use of lasers is not a new concept in neurosurgery, advances in technology have enabled surgeons to perform laser treatment with the aid of real-time MRI thermography as a guide. In this report, we present our institutional series and outcomes of patients treated with LITT. We retrospectively evaluated 19 patients (age range, 28–77 years) who underwent LITT at one or more targets from 2015 to 2019. Primary endpoint observed was mean progression free survival (PFS) and overall survival (OS). Seven patients with glial neoplasms and 12 patients with metastatic disease were reviewed. Average hospitalization was 2.4 days. Median PFS was 7 and 4 months in the metastatic group and primary glial neoplasm group, respectively (p = 0.01). Median OS from time of diagnosis was 41 and 32 months (p = 0.02) and median OS after LITT therapy was 25 and 24 months (p = 0.02) for the metastatic and primary glial neoplasm groups, respectively. One patient experienced immediate post-procedural morbidity secondary to increased intracerebral edema peri-lesionally while one patient experienced post-operative mortality and expired secondary to hemorrhage 1-month post-procedure. Median follow-up was 10 months. Laser interstitial thermal therapy (LITT) is a safe, minimally invasive treatment method that provides surgeons with cytoreductive techniques to treat neurosurgical conditions. Both PFS and OS appear to be more favorable after LITT in patients with metastatic disease. In properly selected patients, this modality offers improved survival outcomes in conjunction with other salvage therapies. [ABSTRACT FROM AUTHOR]

Esophageal carcinoma (EC) and nutritional status are strongly linked due to swallowing disruptions and treatment-related toxicities. Therefore, malnutrition and weight loss (WL) occur in 85% and 79% of EC patients, respectively. WL is frequently associated with worse EC patient outcomes, however, WL during radiation therapy (RT) and EC patient outcomes have not been well established. The purpose of this study is to retrospectively review the association of WL during RT treatment of EC with clinical outcomes. Non-metastatic EC patients from our institution treated between 2010 and 2018, receiving total prescribed dose >40 Gy and aged >18 years, were included. Patients were analyzed by WL during RT, with categories of ≥5% vs. <5% and ≥10% vs. <10%. Patient characteristics and treatment regimens were similar across all WL groups. In univariate analysis, ≥5% and ≥10% WL were significantly associated with both worse overall survival (OS) and progression-free survival (PFS), and ≥10% WL was significantly associated with increased local recurrence. In multivariate analysis, ≥5% WL was significantly associated with OS and PFS. With both ≥5% and ≥10% WL throughout the radiation treatment being detrimental to OS and PFS. The importance of nutritional support in EC patients receiving radiotherapy is further validated. [ABSTRACT FROM AUTHOR]

Annual melanoma incidence in the US is escalating. Comprehensive evaluation of nivolumab alone or with ipilimumab for advanced melanoma treatment. A systematic search was conducted across PubMed, Embase, Web of Science, and Cochrane databases, extending until August 2023. A range of outcomes were evaluated, encompassing overall survival (OS), recurrence-free survival (RFS), progression-free survival (PFS), disease-free survival (DFS), adverse events (both any and serious), complete response rate, mortality rate, and recurrence rate in patients with advanced melanoma. This analysis was conducted on seven relevant studies, involving 2,885 patients. The baseline characteristics of both groups were found to be comparable across all outcomes, with the exception of tumor size. The pooled analysis did not reveal any significant disparities, except for PFS, where the nivolumab-ipilimumab treatment group demonstrated a significantly longer PFS compared to the nivolumab group. However, there was a notable discrepancy in any adverse events (Odds Ratio (OR): 2.69; 95% Confidence Interval (CI): 1.96, 3.69; p < 0.00001) and serious adverse events (OR: 3.59; 95% CI: 2.88, 4.49, p < 0.00001) between the two groups, suggesting that the safety profile of nivolumab combined with ipilimumab was inferior. Given diversity and potential biases, oncologists should base immunotherapy decisions on professional expertise and patient characteristics. PROSPERO registration number: CRD42023453484. [ABSTRACT FROM AUTHOR]

The typical initiating events of a core disruptive accident (CDA) in small sodium-cooled fast reactors (SFR) are evaluated with the computational code, SAS4A. CDA is one of the hypothetical events in the safety assessment of the SFR, as the SFR has the potential to experience power excursion due to the sodium voiding and the core degradation. To improve the safety of future SFRs, the development of SFRs with low void reactivity has been promoted. Small SFRs can have a negative void coefficient of reactivity. The analysis of the CDA event sequence in small SFRs is valuable for the investigation of the reactor characteristics for the future R&D of SFRs. The event progression during ULOF and UTOP, which are the typical initiating events of CDA, is investigated through the numerical analysis. The event progression of these accidents in the low void reactivity reactor is found to be slow due to the effective insertion of the negative reactivity feedback and the absence of significant positive reactivity insertion. No power excursion occurs in the initiating phase. In ULOF, the cladding melt and motion behavior becomes more important for the evaluation of the event progression due to its positive reactivity. [ABSTRACT FROM AUTHOR]

The article discusses the pharmacokinetics of idelalisib, a drug used in the treatment of B-lymphoproliferative disorders. While idelalisib has shown high efficacy, concerns have been raised about severe toxicities associated with the drug. A study was conducted to investigate the link between idelalisib pharmacokinetics and adverse events as well as patient outcomes. The study found that lower exposure to idelalisib was correlated with better outcomes. The authors suggest that a controlled assessment of idelalisib pharmacokinetics could help determine appropriate dosages for patients. [Extracted from the article]

Radioactive iodine (RAI) is often used post-operatively for treatment of differentiated thyroid cancer (DTC), but many patients develop RAI-refractory disease. Patients with RAI-refractory DTC may be asymptomatic and stable for long periods of time, so identifying tumors that are no longer likely to respond to RAI treatment and determining when to transition to systemic therapy are critical issues for optimal patient care. The purpose of this paper is to review and assess the end points used in studies of RAI-refractory DTC in relation to the issues facing clinicians in transitioning patients to systemic therapy. Our goals are to provide a framework to help evaluate whether study results are clinically meaningful in guiding treatment decisions and to make recommendations to better define these end points for RAI-refractory DTC. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is characterized by high rates of recurrence, especially in patients with residual disease after neoadjuvant chemotherapy (NAC). Capecitabine is being used as standard adjuvant treatment in residual TNBC. We aimed to investigate the real-life data regarding the efficacy of capecitabine in residual TNBC. In this retrospective multicenter study, TNBC patients with residual disease were evaluated. Patients, who received standard anthracycline and taxane-based NAC and adjuvant capecitabine were eligible. Overall survival (OS), disease free survival (DFS) and toxicity were analyzed. 170 TNBC patients with residual disease were included. Of these, 62.9% were premenopausal. At the time of analysis, the recurrence rate was 30% and death rate was 18%. The 3-year DFS and OS were 66% and 74%, respectively. In patients treated with adjuvant capecitabine, residual node positive disease stood out as an independent predictor of DFS (p = 0.024) and OS (p = 0.032). Undergoing mastectomy and the presence of T2 residual tumor was independent predictors of DFS (p = 0.016) and OS (p = 0.006), respectively. The efficacy of capecitabine was found lower compared to previous studies. Selected patients may have further benefit from addition of capecitabine. The toxicity associated with capecitabine was found lower than anticipated. [ABSTRACT FROM AUTHOR]

The combination of intravesical gemcitabine (Gem) with docetaxel (Doce) or with mitomycin C (MMC) has been used in the primary setting as an alternative to Bacillus Calmette-Guerin (BCG) to treat high-risk (HR) and intermediate-risk (IR) non-muscle invasive bladder cancer (NMIBC), as well in the rescue setting for patients in whom BCG has failed. Efficacy and safety of Gem/Doce and Gem/MMC to treat NMIBC in BCG-naive and failure settings. In the BCG-naive setting, Gem/Doce was the primary alternative combination therapy reported, with a weighted mean of 12- and 24-month recurrence-free survival (RFS) of 79% and 77% for HR disease and 84% and 76% for IR disease, respectively. In the HR BCG-failure setting, the weighted mean of 12- and 24-month RFS was 60% and 42% for Gem/Doce and 63% and 40% for Gem/MMC. While patients without BCG exposure and papillary disease only benefit the most from Gem/Doce, there is also reasonable efficacy in BCG refractory disease and CIS. Combination therapy is well tolerated, with grade III toxicity reported in less than 1% of patients. Unlike single-agent chemotherapy, intravesical Gem/Doce is considered effective and safe regardless of risk-stratification. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to analyze the survival outcomes and prognostic factors of radiofrequency ablation (RFA) for liver metastases from gastrointestinal stromal tumors (GISTs). Methods: Between March 2011 and November 2022, 34 patients (16 males; age range, 25–72 [median age, 52.5] years) who underwent RFA for liver metastasis from GISTs were included. The mean maximum diameter of metastatic lesions was 2.4 ± 1.0 (range, 1.1–5.2) cm. Survival curves were constructed using the Kaplan–Meier method and compared using the log-rank test. Multivariate analyses were performed using a Cox proportional hazards model. Results: For 79 lesions among 34 patients, all targeted lesions were completely ablated. The mean hepatic progression-free survival (HPFS) period was 28.4 ± 3.8 (range, 1.0–45.7) months. The 1-, 3-, and 5-year HPFS rates were 67.2%, 60.5%, and 20.2%, respectively. Based on the univariate analysis, the number of metastatic tumors and tyrosine kinase inhibitors(TKI) therapy before RFA were prognostic factors for HPFS. Multivariate analysis showed that pre-RFA TKI therapy was associated with a better HPFS(p = 0.030). The mean overall survival (OS) period was 100.5 ± 14.1 (range, 3.8–159.5) months and the 1-, 3-, and 5-year survival rates were 96.9%, 77.1%, and 58.7%, respectively. Both univariate and multivariate analysis indicated that extrahepatic metastasis before RFA (p = 0.044) was a significant prognostic factor for OS. Conclusions: Liver metastases from GIST exhibit relatively mild biological behavior. RFA is safe and effective, particularly in patients without pre-RFA extrahepatic metastases. Patients received targeted therapy before RFA can obtain an extended HPFS. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the cost-effectiveness of adjuvant nivolumab compared with surveillance for the treatment of patients with high-risk muscle-invasive urothelial carcinoma (MIUC) after radical resection from a US healthcare payer perspective and to investigate the impact of alternative modeling approaches on the cost-effectiveness results. Material and methods: A four-state, semi-Markov model consisting of disease free, local recurrence, distant recurrence, and death health states was developed to investigate the cost-effectiveness of nivolumab compared with surveillance over a 30-year time horizon. The model used data from the randomized CheckMate 274 trial (NCT02632409) and published literature to inform transitions among health states, and inputs on cost, utility, adverse event, and disease management. Scenario analyses were conducted to investigate the impact of model structure and key assumptions on the results. One-way deterministic and probabilistic sensitivity analysis were conducted to investigate the robustness of the results. Results: Total expected costs were higher with nivolumab ($162 268) compared with surveillance ($62 965). Nivolumab was associated with improved survival (1.53 life-years gained compared with surveillance) and an incremental gain of 0.94 quality-adjusted life-years (QALYs). Although total treatment costs were higher for nivolumab, cost offsets were observed because of delayed or avoided recurrences and deaths experienced with nivolumab compared with observation. The incremental cost-effectiveness and cost-utility ratios were $64 929/life-year and $105 660/QALY. Limitations: At the time of analysis, CheckMate 274 had limited follow-up on disease-free survival and no overall survival data. The limited evidence necessitated assumptions on modeling survival after each type of recurrence. Conclusions: Nivolumab is estimated to be a life-extending and cost-effective option for adjuvant treatment of MIUC for patients who are at high risk of recurrence after undergoing radical resection in the United States. Using a threshold of $150,000/QALY, the cost-effectiveness conclusions remained consistent across the scenario and sensitivity analyses conducted. [ABSTRACT FROM AUTHOR]

The combination of carmustine, etoposide, cytarabine, and melphalan (BEAM) followed by autologous stem cell transplantation (ASCT) is a commonly used intensification regimen for patients with Hodgkin lymphoma. As etoposide and cytarabine dosing are not defined, we conducted a retrospective, multicenter study, to compare efficacy and toxicity in 130 patients with Hodgkin lymphoma receiving etoposide and cytarabine at either 200 mg/m2/d (n = 50), 400 mg/m2/d (n = 35), or etoposide 200 mg/m2/d and cytarabine 400 mg/m2/d (n = 45). Progression-free survival and overall survival were not associated with the intensity of conditioning. Increased conditioning intensity was associated with longer duration of thrombocytopenia, a higher number of transfused RBC and platelet units and a higher frequency of mucositis, but serious adverse events or infectious complications were not increased. The intensity of BEAM regimen was not associated with survival but with the rate of cytopenia and mucositis advocating for the use of lower dosing in frail patients. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are an emerging tool in the treatment of brain metastases (BMs), Stereotactic radiosurgery (SRS), traditionally used for BMs, elicits an immune brain response and can act synergistically with ICIs. We aim to investigate the efficacy of ICI administered with SRS and determine the impact of timing on BM response. Methods: A systematical search was performed to identify potential studies concerning BMs managed with SRS alone or with SRS + ICI with relative timing administration (ICI concurrent with SRS, ICI noncon-current with SRS, SRS before ICI, SRS after ICI). The overall survival (OS), 12-month OS, local progression-free survival (LPFS), 12-month local brain control (LBC), distant progression-free survival (DPFS), 12-month distant brain control (DBC), and adverse events (intracranial hemorrhage, radionecrosis) were analyzed using the random-effects model. Results: A total of 16 retrospective studies with 1356 BM patients were included. Compared to noncon-current therapy, concurrent therapy revealed a significantly longer OS (HR= 1.43; p = 0.008) and 12-months LBC (HR = 1.91; p = 0.04), a similar 12-months DBC (HR = 1.12; p = 0.547) and higher complication rate (R = 0.77; p = 0.346). Concurrent therapy leads to a significantly higher OS compared to ICI before SRS (HR = 2.55; p = 0.0003). Conclusion: The combination of SRS with ICI improves patients' clinical and radiological outcomes. The effectiveness of the combination is subject to the identification of an optimal therapeutic window. [ABSTRACT FROM AUTHOR]

Low-grade glioma (LGG), which is the second most frequent adult brain malignancy, severely threatens patients' health and has a high recurrence rate. Histone H3/H4 chaperone anti-silencing function 1 B (ASF1B) has a tight association with the initiation and development of tumours. The expression and regulation mechanism of ASF1B in LGG were discussed. ASF1B expression in LGG patients as well as the association of ASF1B with overall survival and disease-free survival of LGG patients were predicted by GEPIA database. The independent prognostic value of ASF1B in LGG patients was investigated by TCGA database. RT-qPCR, together with western blot was applied for the assessment of ASF1B in LGG cell lines. After ASF1B expression was inhibited, CCK8 and colony formation assays judged cell proliferation. Flow cytometry analysis and TUNEL assay appraised cell cycle as well as apoptosis. Cell migratory and invasive capacities were measured by wound healing as well as Transwell assays. Western blot tested the expression of proliferation-, cycle-, apoptosis-, and metastasis-associated proteins. STRING and GeneMANIA database predicted the relationship between ASF1B and tousled-like kinase 1 (TLK1). ChIP assay testified the affinity of ASF1B with TLK1. Subsequently, TLK1 was overexpressed and ASF1B expression interfered, and the functional assays were executed. ASF1B was discovered to be increased in LGG tissues and cells and indicates an unfavourable prognosis for LGG patients. ASF1B was not an independent prognostic factor for LGG. ASF1B deficiency obstructed the proliferation, cell cycle as well as metastasis of LGG cells, and induced cell death, which might be realized through the interaction with TLK1. The interaction between ASF1B and TLK1 promoted the malignant progression of LGG. TLK1 interacts with ASF1B. Interference with ASF1B inhibits the proliferative, invasive and migratory capabilities and induces the cycle arrest, along with the apoptosis of LGG cells. The interaction between ASF1B and TLK1 promotes the malignant progression of LGG. [ABSTRACT FROM AUTHOR]

We aimed to assess the effects of pretreatment neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios on the response to neoadjuvant chemotherapy and survival rates in patients with extremity osteosarcoma. Patients with high-grade osteosarcoma admitted to oncologic centers affiliated with Iran University of Medical Sciences, Tehran, Iran from 2015 to 2021 were evaluated retrospectively to assess the impact of complete blood count-related parameters on the pathologic response after neoadjuvant chemotherapy. Then, patients were followed up prospectively to evaluate the survival rates. All patients received at least three cycles of cisplatin/doxorubicin regimen, preoperatively. In this study, the cut-off values for high neutrophil-to-lymphocyte and high platelet-to-lymphocyte ratio were considered 3.28 and 128, respectively. One hundred eighty-six patients were enrolled. Patients with high neutrophil-to-lymphocyte ratio and high platelet-to-lymphocyte ratio had a significantly lower overall survival rates (20.7 [95% CI 18–23.5] month vs. 34.6 [95% CI 33.2–36], p = 0.003 and 21.9 [95% CI 20.2–23.6] month versus 35.3 [95% CI 33.9–36.7], p = 0.002; respectively). Moreover, disease-free survival of patients with high platelet-to-lymphocyte ratio was worse than patients with low platelet-to-lymphocyte ratio (20.4 [95% CI 18.4–22.4] month vs. 32.7 [95% CI 30.8–34.7], p = 0.02). Our study showed that neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios at the baseline can predict the survival of patients with high-grade osteosarcoma. [ABSTRACT FROM AUTHOR]

The current systematic analysis and meta-analysis was aimed to evaluate the association between radiation-induced lymphopenia (RIL) and survival of women with cervical cancer (CC). PubMed, Embase, Web of Science, and Cochrane Library were searched for relevant cohort studies comparing survival between women with CC who developed versus not developed RIL after radiotherapy. We pooled the results using a random-effects model that incorporates heterogeneity. In the meta-analysis, 952 women with CC were included from eight cohort studies. Overall, 378 (39.7%) of them had RIL after radiotherapy. During a median follow-up duration of 41.8 months, pooled results showed that RIL was independently associated with poor overall survival (hazard ratio [HR]: 2.67, 95% confidence interval [CI]: 1.81 to 3.94, p < 0.001; I2 = 20%) and progression-free survival (HR: 2.17, 95% CI: 1.58 to 2.98, p < 0.001; I2 = 0%). Predefined subgroup analyses showed similar results in patients with grade 3-4 and grade 4 RIL, in patients with RIL diagnosed during or after the radiotherapy, and in studies with quality score of seven or eight points (p values for subgroup effect all < 0.05). In conclusion, women with RIL were associated with poor survival after radiotherapy for CC. [ABSTRACT FROM AUTHOR]

Chinese medicinal herbs (CMH) have been considered a potentially efficacious approach for patients with breast cancer that experience adverse effects from endocrine treatment. To investigate the impact of CMH on endocrine therapy-induced side effects in patients with hormone receptor-positive (HR+) breast cancer. Ten databases (e.g., PubMed, Web of Science, Cochrane Library, China National Knowledge Information Database and other databases) were searched up to 20 May 2022. The search terms included Chinese herb, breast cancer, endocrine therapy, clinical trial and their mesh terms. The study selection and data extraction were performed by two independent reviewers. The risk of bias was evaluated using the Cochrane risk of bias method. A total of 31 studies with 2288 patients were included. There were significant improvements in bone mineral density (BMD) [lumbar BMD (MD 0.08, 95% CI 0.07 to 0.09, p < 0.00001) and femoral neck BMD (MD 0.08, 95% CI 0.07 to 0.10, p < 0.00001)] and bone gal protein (BGP) (MD 0.24, 95% CI 0.17 to 0.31, p < 0.00001), with a significant reduction in triglycerides (MD −0.53, 95% CI −1.00 to −0.07, p < 0.05) and no effect on estradiol levels (MD 0.90, 95% CI −0.31 to 2.12, p = 0.15). CMH combined with complementary therapy can moderately reduce endocrine therapy-induced side effects, including bone loss and dyslipidemia in patients with HR + breast cancer, revealing the potential role of CMH in treating (HR+) breast cancer. More high-quality RCTs are warranted to further validate the effectiveness and safety of CMH. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are one of the most promising approaches toward advanced melanoma. Here, we aimed to perform a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of all studied ICIs. We conducted a comprehensive search to identify the relevant publications (PROSPERO registration ID: CRD42023470649). Then we performed a meta-analysis to evaluate the efficacy of different ICIs for metastatic melanoma. We used Cochrane's tool to assess the quality of studies. The outcome measures were overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS). Twenty reports of RCTs entered our systematic review, 18 of which were included in our data analysis. ICIs showed improved survival compared with control group (hazard ratio (HR) = 0.57; 95% CI: 0.43–0.71; P<0.001). Using a meta-regression, we found a significant relation between patients' mean age and their OS (P<0.001, ${{\rm{R}}^2}$ R 2 = 100.00%). Also, our analysis revealed greater HR for CTLA-4 inhibitors than PD-1/PD-L1 inhibitors (HR = 0.71, 95%CI: 0.63–0.79, P<0.001 vs. HR = 0.63, 95%CI: 0.46–0.79, P<0.001). The effect sizes of different types of PD-1/PD-L1 inhibitors were comparable Our results suggest that ICI-based immunotherapy is associated with enhanced OS, PFS, and RFS (P < 0.001) and will assist clinicians in choosing the optimal approach toward treating metastatic melanoma. [ABSTRACT FROM AUTHOR]

We aimed to describe the clinical efficacy and safety of tislelizumab, a new (PD-1) inhibitor, in patients with malignant solid tumors. We searched relevant databases for phase III randomized controlled trials, including patients with solid tumors. The following outcomes are of interest: overall response rate (OS), overall survival (ORR), progression-free survival (PFS), disease control rate (DCR), and treatment-related adverse events (TRAE). We conducted subgroup analyses based on the line of therapy, type of solid tumor, and tislelizumab alone or combined with chemotherapy. Seven phase III RCTs with 3478 were included in the meta-analysis. Pooled analysis demonstrated that tislelizumab significantly improved ORR and DCR with (OR) of 2.59 (95% (CI) = 2.15–3.12, p < 0.00001) and 1.78 (95% CI = 1.43–2.21, p > 0.00001), respectively. Pooled HRs for OS and PFS were 0.71 (95% CI = 0.65-0.78, p > 0.00001) and 0.68 (95% CI = 0.54–0.84, p = 0.0005), respectively. Overall, based on this meta-analysis, the available data strongly supports the utilization of tislelizumab in the treatment of malignant solid tumors. CRD42023408815 [ABSTRACT FROM AUTHOR]

This meta-analysis aims to systematically analyze the efficacy and toxicity of mirvetuximab soravtansine (MIRV) as second-line and above treatment for advanced or recurrent ovarian cancer. Candidate studies were identified in PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases up to 1 May 2023. Objective response rate (ORR), progression-free survival (PFS), the incidence of adverse events (AEs), and incidence of grade ≥ 3 AEs were extracted and calculated by meta-analysis of merging ratios or mean to describe the efficacy and toxicity of MIRV. Seven eligible prospective studies were included in this meta-analysis, including 605 patients with advanced ovarian cancer who received second-line or higher therapy. ORR of MIRV was 34.2% (95% confidence interval [CI] 25.0–43.5), and PFS was 5.82 months (95%CI 4.47–7.18). The overall incidence of AEs was 87.4% (95%CI 52.9–100.0) and the incidence of grade ≥ 3 AEs was 27.1% (95%CI 18.9–36.1). The most common AEs were vision blurring, nausea, and diarrhea, with incidence of 46.7% (39.6–53.8), 41.8% (34.0–49.9), and 41.3% (30.4–52.5), respectively. MIRV has definite efficacy and good safety as a novel choice for second-line and above treatment of advanced or recurrent FRα positive ovarian cancer. This may have promising application in patients with platinum-resistant diseases. CRD42023428599 [ABSTRACT FROM AUTHOR]

The soluble programmed death ligand-1 (sPD-L1) and its prognostic role in cancers have been investigated in numerous studies. However, due to the inconsistency on some findings, this meta-analysis was performed to assess the prognostic value of sPD-L1 in patients with cancer. We searched the PubMed, Web of Science, MEDLINE, Wiley Online Library and ScienceDirect, and screened the studies for eligibility. Recurrence-free survival (RFS), progression-free survival (PFS) and disease-free survival (DFS) were for short term survival. The overall survival (OS) was for long term survival. Forty studies with 4441 patients were included in this meta-analysis. Elevated sPD-L1 was associated with short OS [HR = 2.44 (2.03–2.94), p = 0.000]. Moreover, a high sPD-L1 was predictive of worse DFS/RFS/PFS [HR = 2.52 (1.83–3.44), p = 0.000]. In addition, high sPD-L1 was consistently correlated with poor OS in irrespective of study type, univariate and multivariate analysis, ethnicity, cut-off value of sPD-L1, sample and treatment. In the subgroup analysis, high sPD-L1 was correlated with poor OS in gastrointestinal cancer, lung cancer, hepatic cancer, oesophageal cancer and clear cell renal cell carcinoma. The present meta-analysis showed that a high level of sPD-L1 was associated with worse prognosis in some types of cancer. [ABSTRACT FROM AUTHOR]

This meta-analysis was conducted to systematically evaluate the prognostic role of the Naples prognostic score (NPS) in patients with gastrointestinal (GI) cancers. A comprehensive literature search of several major databases was performed for studies published until October 16, 2022. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted and pooled by fixed-effects or random-effects models to analyze the associations between the NPS and overall survival (OS), cancer-specific survival (CSS), and recurrence-free/disease-free survival (RFS/DFS) in GI cancers. Thirteen studies were included in the meta-analysis. Pooled results indicated that a high NPS predicted poor OS (HR = 2.28, 95% CI: 1.90–2.74, p < 0.001), CSS (HR = 2.77, 95% CI: 2.10–3.66, p < 0.001), and RFS/DFS (HR = 2.77, 95% CI: 2.26–3.40, p < 0.001). For OS-related and RFS/DFS-related studies, subgroup analyses showed that a high NPS was significantly associated with poor OS and RFS/DFS irrespective of NPS group, calculation of the NPS, and tumor type. In the study that focused on CSS, subgroup analyses by NPS group and calculation of the NPS revealed similar results. The NPS may represent an effective prognostic indicator in patients with GI cancers. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is a biologically and clinically heterogeneous disease, emphasizing the need for prognostic biomarkers. In this study we aimed at comparing the prognostic value of two RNA-based risk scores, circSCORE and MCL35, in 149 patients from the MCL2 (ISRCTN87866680) and MCL3 (NCT00514475) patient cohorts. Both risk scores provided significant stratification of high versus low risk for progression free survival (PFS) and overall survival (OS). The circSCORE retained significant prognostic value in adjusted multivariable Cox regressions for PFS, but not for OS. Furthermore, circSCORE added significant prognostic value to MIPI in the pooled cohort (MCL2 and MCL3) for PFS and OS, and for PFS in MCL3 alone, outperforming Ki67 and MCL35. We suggest a new, combined MIPI-circSCORE with improved prognostic value, and with potential for future clinical implementation, if validated in a larger, independent cohort. [ABSTRACT FROM AUTHOR]

This systematic review with embedded meta-analysis aimed to evaluate the clinical utility of circulating tumor DNA (ctDNA) in lung cancer. After screening and review of the Embase database search, 111 studies from 2015 to 2020 demonstrated ctDNA's value in prognostication/monitoring disease progression, mainly in patients with advanced/metastatic disease and non–small cell lung cancer. ctDNA positivity/detection at any time point was associated with shorter progression-free survival and overall survival, whereas ctDNA clearance/decrease during treatment was associated with a lower risk of progression and death. Validating these findings and addressing challenges regarding ctDNA testing integration into clinical practice will require further research. [ABSTRACT FROM AUTHOR]

Whether palliative RT (pRT) can influence the prognosis of mNSCLC patients who are treated with immune checkpoint inhibitors (ICIs) is still under debate. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of pRT plus ICIs in mNSCLC patients. PubMed, Cochrane, and Embase databases were searched, and only prospective studies and randomized controlled trials (RCTs) were included. All data were analyzed with Stata 14.0 and Review Manager Version 5.4 software. A total of 13 studies were included. The combined ORRs for the ICIs group, cRT plus ICIs group, and SBRT plus ICIs group were 0.22 (95% CI: 1.27, 4.04), 0.26 (95% CI: 0.04, 0.49), and 0.29 (95% CI: 0.17, 0.40), respectively. And PFS were 2.21 (95% CI: 1.71, 2.70), 4.63 (95% CI: 2.16, 7.09), and 7.38 (95% CI: 2.16, 12.60) months, respectively. OS was 5.96 (95% CI: 3.85, 8.07), 9.04 (95% CI: 6.49, 11.59), and 7.96 (95% CI: 4.02, 11.91) months for the above groups, respectively. For safety terms, patients receiving ICIs plus SBRT had an incidence of 5% (95% CI: 2%, 9%) for pneumonia. Patients with mNSCLC may benefit from the combination of ICIs and pRT therapy, but these findings need further validation. [ABSTRACT FROM AUTHOR]

To systematically assess the predictive significance of systemic immune-inflammation index (SII) in renal cell carcinoma (RCC). Relevant studies published before November 2022 were retrieved from public databases. Hazard ratio (HR), standardised mean difference (SMD) and relative risk (RR) were calculated to estimate associations of SII with prognosis, treatment responses and clinicopathological features. Twenty studies involving 6887 patients were eligible. The meta-analysis results revealed a high SII level was associated with worse overall survival (HR: 1.45, p < 0.001), progression-free survival (HR: 1.63, p = 0.001), cancer-specific survival (HR: 1.86, p < 0.001), lower overall response rate (RR: 0.62, p = 0.003), disease control rate (RR: 0.69, p = 0.002), larger tumour size (SMD: 0.39, p = 0.001), poorer IMDC risk (RR: 7.09, p < 0.001), higher Fuhrman grade (RR: 1.54, p = 0.004), tumour stage (RR: 1.67, p = 0.045), the presence of distant metastasis (brain: RR, 2.04, p = 0.001; bone: RR, 1.33, p = 0.024) and tumour necrosis (RR: 1.57, p = 0.031). Subgroup analysis showed SII predicted OS and PFS for non-Asian, but CSS for both Asian and non-Asian populations. Pre-treatment SII may be a promising predictor of clinical outcomes for RCC patients. [ABSTRACT FROM AUTHOR]

Desmoplastic small round cell tumor (DSRCT) is an extremely rare and highly aggressive soft tissue sarcoma, presenting mainly in male adolescents and young adults with multiple nodules disseminated within the abdominopelvic cavity. Despite a multimodal approach including aggressive cytoreductive surgery, intensive multi-agent chemotherapy, and postoperative whole abdominopelvic radiotherapy, the prognosis for DSRCT remains dismal. Median progression-free survival ranges between 4 and 21 months, and overall survival between 17 and 60 months, with the 5-year overall survival rate in the range of 10–20%. This review discusses the treatment strategies used for DSRCT over the years, the state of the art of current treatments, and future clinical prospects. The unsatisfactory outcomes for patients with DSRCT warrant investigations into innovative treatment combinations. An international multidisciplinary and multi-stakeholder collaboration, involving both pediatric and adult sarcoma communities, is needed to propel preclinical model generation and drug development, and innovative clinical trial designs to enable the timely testing of treatments involving novel agents guided by biology to boost the chances of survival for patients with this devastating disease. [ABSTRACT FROM AUTHOR]

Family with sequence similarity of 83D (FAM83D) is overexpressed in various cancers. However, no pan-cancer analysis is presently available. In the present study, we used a bioinformatics analysis to explore the diagnostic and prognostic value of FAM83D expression levels in human cancers. The GEPIA 2, TIMER 2.0, ENCORI, and DriverDBV3 databases were used to evaluate FAM83D expression levels. The potential prognostic value of FAM83D expression was analyzed using the GEPIA 2, UALCAN, and TISIB databases. The driver gene and promoter methylation levels regarding FAM83D were evaluated using the TIMER 2.0 and UALCAN databases. To further analyze interactive networks for FAM83D, FAM83D-binding proteins and related genes were determined using STRING and Gene MANIA analytic tools. Highly expressed FAM83D could be associated with mutated TP53 and promoter DNA methylation. Relative network analysis suggested that FAM83D was mainly involved in the progesterone-mediated oocyte maturation pathway, cell cycle regulation, and several other signaling pathways. Therefore, the differential expression of FAM83D could serve as a diagnostic and prognostic biomarker for various cancers. Our study revealed useful information about the differential expression of FAM83D, prognostic values, and potential functional networks in a variety of cancers, providing valuable substantive and methodological information to explore the underlying mechanisms. Abbreviations: BP: Biological processes; CC: Cellular components; DAVID: Database for Annotation, Visualization, and Integrated Discovery; DFS: Disease-free survival; ENCORI: Encyclopedia of RNA Interactomes; FAM83: Family with sequence similarity 83; FAM83D: Family with sequence similarity of 83D; GEO: Gene Expression Omnibus; GEPIAx2: Gene Expression Profiling Interactive Analysis 2; GO: Gene Ontology; GTEx: Genotype-Tissue Expression; KEGG: Kyoto Encyclopedia of Genes and Genomes; KIRC: Kidney renal clear cell carcinoma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; MF: Molecular functions miRNA: microRNA; OS: Overall survival; PAAD: Pancreatic adenocarcinoma; PPI: Protein – protein interaction; RNA-seq: RNA-sequencing; TCGA: The Cancer Genome Atlas; TIMER 2.0: Tumor Immune Estimation Resource 2.0; UALCAN: University of Alabama at Birmingham Cancer; UCEC: Uterine corpus endometrial carcinoma. [ABSTRACT FROM AUTHOR]

Predicting time-to-death for patients is one of the most important issues in survival analysis. A dynamic prediction method using a bivariate failure time model allows one to build a prediction formula based on tumor progression status observed during the follow-up. However, the existing spline models for the baseline hazard functions are not convenient for predicting long-term survival probability exceeding the largest follow-up time. Therefore, we proposed a parametric method based on the Weibull model to achieve long-term prediction. The present study aims to develop a prediction formula based on a Weibull-based bivariate failure time model, which is designed for individual patient data meta-analysis. We also consider prediction of residual life expectancy that is not possible by the nonparametric models. We conducted Monte Carlo simulations to compare the performance of the proposed model with the spline model. In addition, we illustrate the proposed methods through the analysis of breast cancer patients. [ABSTRACT FROM AUTHOR]

In the ZUMA-5 trial (Clinical trials identification: NCT03105336), axicabtagene ciloleucel (axi-cel; a chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory (r/r) follicular lymphoma (FL) patients and clear superiority relative to the SCHOLAR-5 external control cohort. We update this comparison using the ZUMA-5 24-month data. The SCHOLAR-5 cohort is comprised of r/r FL patients who initiated ≥3rd line of therapy after July 2014 and meeting ZUMA-5 eligibility criteria. Groups were balanced for patient characteristics through propensity scoring on prespecified prognostic factors using standardized mortality ratio (SMR) weighting. The overall response rate was compared using a weighted logistic regression. Time-to-event outcomes were evaluated using a Cox regression. For SCHOLAR-5, the sum of weights for the 143 patients was 85 after SMR weighting, versus 86 patients in ZUMA-5. The median follow-up was 29.4 months and 25.4 months for ZUMA-5 and SCHOLAR-5, respectively. The hazard ratios for overall survival and progression-free survival were 0.52 (95% confidence interval (CI): 0.28–0.95) and 0.28 (95% CI: 0.17–0.45), favoring axi-cel. This updated analysis, using a longer minimum follow-up than a previously published analysis, shows that the improved efficacy of axi-cel, relative to available therapies, in r/r FL is durable.. [ABSTRACT FROM AUTHOR]

The paradigm of focal therapy's role in metastatic patients is being challenged by evolving attitudes and emerging data. At the current time, specifically regarding prostate cancer, does the evidence indicate this is more hype or hope? We searched the literature via PubMed, MEDLINE, and Embase for studies from 2014 to the present addressing focal therapy with non-palliative intent in metastatic prostate cancer patients, emphasizing prospective trials when available. We sought to address all common clinical scenarios: de novo synchronous diagnosis, oligorecurrence, oligoprogression, and mCRPC disease. Current evidence is strongest, and in our opinion practice-changing, for prostate-directed RT in de novo metastatic patients with low metastatic burden. Metastasis-directed therapy with SBRT is consistently shown to have low rates of toxicity, and promising rates of ADT-free survival and progression-free survival. These can be utilized on a patient-by-patient basis with these endpoints in mind, but do not yet show sufficient benefit to be standard of care. This is a rich area of ongoing research, and many trials should publish in the coming years to shed light on many unanswered questions, including the role of cytoreductive prostatectomy, systemic therapy combined with MDT, and the integration of modern PET imaging. [ABSTRACT FROM AUTHOR]

To investigate the impact of radiation dose on the efficacy of definitive chemoradiotherapy(dCCRT) in patients with locally advanced esophageal carcinoma. PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Wanfang, and Chinese National Knowledge Infrastructure(CNKI) were searched for eligible studies. Studies that compared high-dose radiation(HD-RT) group with low-dose radiation(LD-RT) group using modern radiotherapy techniques for locally advanced esophageal carcinoma patients in dCCRT were identified. The hazard ratios (HR) for overall survival (OS), progression-free survival (PFS), and the odds ratios (OR) for clinical complete response (cCR), local--regional failure (LRF), distant metastasis (DM), and grade≥3 AEs. Meta-analysis was performed when relevant data were available. Eleven studies involving 1943 patients were included for analyses. The results showed that the HD-RT group had better OS (pooled HR 0.78 [0.70, 0.87], p < .00001), PFS (pooled HR 0.72 [0.55, 0.94], p = .01), cCR (OR 1.52 [1.13, 2.05], p = .005), and LRF (OR 0.60 [0.45, 0.80], p = .0004). In addition, there were no significant differences between the two groups in terms of DM (OR 1.43 [1.00, 2.04], p = .05), grade 3--5 radiation pneumonitis (OR 1.38 [0.71, 2.68], p = .35), grade 3-5 radiation esophagitis (OR 1.36 [0.88, 2.10], p = .17), grade 3-5 other esophageal toxicities(stenosis/fistula/hemorrhage) (OR 1.22 [0.75, 2.00], p = .43), and treatment-related death (OR 1.40 [0.73, 2.68], p = .31). High-dose radiotherapy in definitive CCRT for patients with locally advanced esophageal carcinoma is associated with improved PFS, OS, cCR, and LC with no increase of grade≥3AEs. Simultaneously, we await the preliminary and final results of several ongoing dose-escalation randomized trials. Furthermore, future studies should provide personalized radiotherapy doses for these patients. [ABSTRACT FROM AUTHOR]

Immunotherapy of lung cancer has achieved promising clinical results. However, it is urgent to develop predictive biomarkers for effective immunotherapy. While ferroptosis plays a critical role in immunotherapy efficacy, ferritin is an important regulatory factor. We, therefore, hypothesize that basal serum ferritin levels before immunotherapy and their corresponding changes during immunotherapy can be useful predictors of immunotherapy response in patients with lung cancer. We measured serum ferritin levels in 107 patients with lung cancer before and during immune checkpoint blockade treatments and studied the correlation between ferritin levels, response rate, and survival. Moreover, the correlation between basal ferritin and PD-L1 expression, tumor stages and pathological types was also analyzed. Patients with lower basal serum ferritin levels before immunotherapy had longer progression-free survival (PFS) (median 7 vs 4 months, P = .023) and higher disease control rate (DCR) (X² = 4.837, P = .028), those with downregulated serum ferritin levels during immunotherapy correlated with longer PFS (median 9.5 vs 4 months, P < .001) and higher DCR (X² = 6.475, P = .011). However, the "integrated factor", which was calculated as the combination of lower basal serum ferritin levels before immunotherapy and downregulated serum ferritin levels during immunotherapy, correlated with prolonged PFS (P < .001). Multivariate analyses revealed that the basal serum ferritin levels before immunotherapy and the corresponding changes during immunotherapy were both strong independent prognostic factors (hazard ratio (HR) = 1.60, P = .041; HR = 2.65, P = .001). These findings suggest that serum ferritin levels can be used as a prognostic biomarker for lung cancer in predicting immunotherapy efficacy. [ABSTRACT FROM AUTHOR]