Clinical features and treatment outcomes of intraocular and ocular adnexal metastasis.

The aim of this study was to investigate the primary sites, clinical characteristics, and treatment outcomes of patients with metastatic tumors in the eye and ocular adnexa. This retrospective case series consisted of 42 patients diagnosed with intraocular metastasis (IM) or ocular adnexal metastasis (OAM) at a tertiary center between January 2001 and June 2023. The patients comprised 18 men and 24 women; 24 (57%) and 18 (43%) patients were diagnosed with IM and OAM, respectively. In the IM group, the primary tumors originated from the lungs (79%), followed by the breasts (17%). In the OAM group, the primary tumors originated from the breasts (33%). Previously, 57% of the patients had been diagnosed with cancer. In the IM group, 38% exhibited bilateral involvement. Only 6% of the patients with OAM had bilateral diseases. The 1-, 3-, and 5-year overall survival (OS) was 42%, 18%, and 7%, respectively. The median OS since metastasis diagnosis in the lungs and breast was 11.8 and 10.5 months, respectively. Lung cancer remains the predominant primary cancer in IM, whereas breast cancer is the major cancer in OAM. Despite poor OS, early detection will facilitate the prompt treatment of primary cancer and metastatic sites.

A clinical tool to predict overall survival of elderly patients with soft tissue sarcoma after surgical resection.

With the aging world population, the incidence of soft tissue sarcoma (STS) in the elderly gradually increases and the prognosis is poor. The primary goal of this research was to analyze the relevant risk factors affecting the postoperative overall survival in elderly STS patients and to provide some guidance and assistance in clinical treatment. The study included 2,353 elderly STS patients from the Surveillance, Epidemiology, and End Results database. To find independent predictive variables, we employed the Cox proportional risk regression model. R software was used to develop and validate the nomogram model to predict postoperative overall survival. The performance and practical value of the nomogram were evaluated using calibration curves, the area under the curve, and decision curve analysis. Age, tumor primary site, disease stage, tumor size, tumor grade, N stage, and marital status, are the risk variables of postoperative overall survival, and the prognostic model was constructed on this basis. In the two sets, both calibration curves and receiver operating characteristic curves showed that the nomogram had high predictive accuracy and discriminative power, while decision curve analysis demonstrated that the model had good clinical usefulness. A predictive nomogram was designed and tested to evaluate postoperative overall survival in elderly STS patients. The nomogram allows clinical practitioners to more accurately evaluate the prognosis of individual patients, facilitates the progress of individualized treatment, and provides clinical guidance.

Advancing lung adenocarcinoma prognosis and immunotherapy prediction with a multi-omics consensus machine learning approach.

Lung adenocarcinoma (LUAD) is a tumour characterized by high tumour heterogeneity. Although there are numerous prognostic and immunotherapeutic options available for LUAD, there is a dearth of precise, individualized treatment plans. We integrated mRNA, lncRNA, microRNA, methylation and mutation data from the TCGA database for LUAD. Utilizing ten clustering algorithms, we identified stable multi-omics consensus clusters (MOCs). These data were then amalgamated with ten machine learning approaches to develop a robust model capable of reliably identifying patient prognosis and predicting immunotherapy outcomes. Through ten clustering algorithms, two prognostically relevant MOCs were identified, with MOC2 showing more favourable outcomes. We subsequently constructed a MOCs-associated machine learning model (MOCM) based on eight MOCs-specific hub genes. Patients characterized by a lower MOCM score exhibited better overall survival and responses to immunotherapy. These findings were consistent across multiple datasets, and compared to many previously published LUAD biomarkers, our MOCM score demonstrated superior predictive performance. Notably, the low MOCM group was more inclined towards 'hot' tumours, characterized by higher levels of immune cell infiltration. Intriguingly, a significant positive correlation between GJB3 and the MOCM score (R = 0.77, p < 0.01) was discovered. Further experiments confirmed that GJB3 significantly enhances LUAD proliferation, invasion and migration, indicating its potential as a key target for LUAD treatment. Our developed MOCM score accurately predicts the prognosis of LUAD patients and identifies potential beneficiaries of immunotherapy, offering broad clinical applicability.

Long-term outcomes of the BalMedic bovine pericardial bioprosthetic valve in female patients ≤50 years: a multicenter retrospective study.

Background: A bioprosthetic valve is recommended for women of childbearing age who require cardiac valve replacement in order to minimize the risk of blood clot formation. However, it should be noted that compared to mechanical valves, bioprosthetic valves have a shorter lifespan and a higher likelihood of requiring reoperation during follow-up. To assess the long-term postoperative results, including the incidence of structural valve deterioration (SVD) and other clinical outcomes, in female patients aged 50 years and younger who underwent BalMedic bovine pericardial bioprosthetic valve replacement, a multicenter retrospective study was implemented in China. Methods: Between 2004 and 2015, a cohort of 86 female patients across three medical centers underwent the implantation of 97 bioprosthetic valves. The primary outcome measure was overall survival (OS), while the secondary outcome measures were preliminary evidence of reoperation, SVD incidence, and bioprosthetic valve-related complications. Results: In this cohort study, 21 patients (24.4%, 21/86) died, while 37 patients (43.0%, 37/86) underwent a second valve replacement. The OS rates at 5 and 10 years were 97.56% and 71.93%, respectively. Additionally, the reoperation-free rates at 5 and 10 years were 92.83% and 80.68%, respectively. Similarly, the rates of freedom from SVD at 5 and 10 years were 95.65% and 51.82%, respectively, and the average duration of bioprosthetic valve replacement in our study was 9.34±3.31 years. Conclusions: Despite the recruitment of younger female patients of child-bearing age in our cohort, the OS, reoperation-free survival, and SVD-free rates of the BalMedic bovine pericardial bioprosthetic valve were not inferior to those of the other age groups in the study or those reported in the literature.

Efficacy of cytoreductive surgery for metastatic upper tract urothelial carcinoma: a Surveillance, Epidemiology and End Results (SEER) study of 508 patients.

Background: Cisplatin-based combination chemotherapy alone is currently considered the standard of care for patients with metastatic upper tract urothelial carcinoma (mUTUC). However, less research has been done on the efficacy of other combinations. In this study, we explored the role of cytoreductive surgery in patients with mUTUC receiving different types of systemic therapy. Methods: Data from 9,436 anonymized records were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2008-2018. Of these, 508 individuals received systemic therapy subsequent to being diagnosed with mUTUC. These patients had all been treated with systemic therapies such as chemotherapy and/or radiotherapy. Patients were stratified into either a non-surgical or surgical group based on cytoreductive surgery status before systemic therapeutics commenced. Kaplan-Meier curves were used to compare overall survival (OS) and cancer-specific survival (CSS). Cox's proportional hazard models were then used to analyze prognostic factors related to OS and CSS. Results: Of the 508 cases, 36.8% (n=187) had received cytoreductive surgery with systemic treatments. The remaining 63.2% (n=321) received either chemotherapy and/or radiotherapy alone. Kaplan-Meier curves showed that 11.6% had 3-year OS [95% confidential interval (CI): 7.1-17.3] for cytoreductive surgery with systemic treatment and 4.9% (95% CI: 2.7-8.0) for systemic treatment alone (P=0.001). The 3-year CSS was 14.9% for cytoreductive surgery plus systemic treatment (95% CI: 9.4-21.7%) and 6.0% (95% CI: 3.4-9.8%) for systemic treatments alone (P=0.003). Under multivariate regression analysis, primary ureter site OS had a hazard ratio (HR) of 0.74 (95% CI: 0.58-0.95, P=0.02) and a CSS HR of 0.72 (95% CI: 0.56-0.94, P=0.01). The cytoreductive surgery OS HR was 0.79 (95% CI: 0.65-0.95, P=0.02) and the CSS HR was 0.75 (95% CI: 0.61-0.92, P=0.006). Additionally, chemotherapy had an OS HR of 0.46 (95% CI: 0.33-0.0.65, P<0.001) and a CSS HR of 0.44 (95% CI: 0.31-0.63, P<0.001). Bones and liver metastases were also indicative of poorer prognosis. Validation was conducted through subgroup analysis which suggested cytoreductive surgery was effective only for patients who received chemotherapy or combined chemo-radiotherapy but not for radiotherapy alone. Conclusions: Cytoreductive surgery provided significantly increased OS and CSS for mUTUC patients who received chemotherapy or combined chemo-radiotherapy in this study. In addition, the primary tumor and metastatic sites were shown to be related to improved patient survival although this was a small and relatively homogeneous cohort of study, sample therefore, further research is required.

Anxiety symptoms predict head and neck cancer survival: Exploring mediation by systemic inflammation and tumor response to treatment.

BACKGROUND: Head and neck cancers (HNC) are associated with high rates of anxiety. Anxiety has been linked to biological pathways implicated in cancer progression, though little is known about its effects on overall survival. We hypothesized that higher pretreatment anxiety levels in patients with HNC would predict poorer 2-year overall survival and expected this relationship to be mediated by both systemic inflammation and tumor response to treatment. METHODS: Patients (N = 394) reported anxiety symptomatology via the GAD-7 at treatment planning. Pre-treatment hematology workup provided an index of systemic inflammation (SII; N = 292). Clinical data review yielded tumor response and overall survival. Logistic and multiple regressions and Cox proportional hazard models tested hypothesized relationships. RESULTS: Higher pretreatment anxiety levels were significantly associated with poorer 2-year survival (hazard ratio [HR], 1.039; 95% confidence interval [CI], 1.014-1.066, p = 0.002). The association between anxiety and SII was not significant, though anxiety was associated with poorer tumor response (odds ratio [OR], 1.033; 95% CI, 1.001-1.066, p = 0.043). Tumor response fully mediated the relationship between anxiety symptoms and 2-year survival (HR, 9.290, 95% CI, 6.152-14.031, p < 0.001). CONCLUSIONS: Anxiety was associated with overall survival. Tumor response, but not systemic inflammation, emerged as a potential biological pathway mediating this effect. Screening for anxiety may be beneficial to help prospectively address these concerns and ameliorate potentially detrimental impact on clinically meaningful cancer outcomes.

Survival of patients with lymph node versus bone versus visceral metastases according to CHAARTED/LATITUDE criteria in the era of intensified combination therapies for metastatic hormone-sensitive prostate cancer.

BACKGROUND: The first approvals of novel systemic therapies within recent years for metastatic hormone-sensitive (mHSPC) were mainly based on improved overall survival (OS) and time to castration resistance (ttCRPC) in mHSPC patients stratified according to CHAARTED low (LV) versus high volume (HV) and LATITUDE low (LR) versus high-risk (HR) disease. METHODS: Relying on our institutional tertiary-care database we identified all mHSPC stratified according to CHAARTED LV versus HV, LATITUDE LR versus HR and the location of the metastatic spread (lymph nodes (M1a) versus bone (M1b) versus visceral/others (M1c) metastases. OS and ttCRPC analyses, as well as Cox regression models were performed according to different metastatic categories. RESULTS: Of 451 mHSPC, 14% versus 27% versus 48% versus 12% were classified as M1a LV versus M1b LV versus M1b HV versus M1c HV with significant differences in median OS: 95 versus 64 versus 50 versus 46 months (p < 0.001). In multivariable Cox regression models HV M1b (Hazard Ratio: 2.4, p = 0.03) and HV M1c (Hazard Ratio: 3.3, p < 0.01) harbored significant worse than M1a LV mHSPC. After stratification according to LATITUDE criteria, also significant differences between M1a LR versus M1b LR versus M1b HR versus M1c HR mHSPC patients were observed (p < 0.01) with M1b HR (Hazard Ratio: 2.7, p = 0.03) and M1c HR (Hazard Ratio: 3.5, p < 0.01), as predictor for worse OS. In comparison between HV M1b and HV M1c, as well as HR M1b versus HR M1c no differences in ttCRPC or OS were observed. CONCLUSIONS: Significant differences exist between different metastatic patterns of HV and LV and HR and LR criteria. Best prognosis is observed within M1a LV and LR mHSPC patients.

Metabolism score and machine learning models for the prediction of esophageal squamous cell carcinoma progression.

The incomplete prediction of prognosis in esophageal squamous cell carcinoma (ESCC) patients is attributed to various therapeutic interventions and complex prognostic factors. Consequently, there is a pressing demand for enhanced predictive biomarkers that can facilitate clinical management and treatment decisions. This study recruited 491 ESCC patients who underwent surgical treatment at Huashan Hospital, Fudan University. We incorporated 14 blood metabolic indicators and identified independent prognostic indicators for overall survival through univariate and multivariate analyses. Subsequently, a metabolism score formula was established based on the biochemical markers. We constructed a nomogram and machine learning models utilizing the metabolism score and clinically significant prognostic features, followed by an evaluation of their predictive accuracy and performance. We identified alkaline phosphatase, free fatty acids, homocysteine, lactate dehydrogenase, and triglycerides as independent prognostic indicators for ESCC. Subsequently, based on these five indicators, we established a metabolism score that serves as an independent prognostic factor in ESCC patients. By utilizing this metabolism score in conjunction with clinical features, a nomogram can precisely predict the prognosis of ESCC patients, achieving an area under the curve (AUC) of 0.89. The random forest (RF) model showed superior predictive ability (AUC = 0.90, accuracy = 86%, Matthews correlation coefficient = 0.55). Finally, we used an RF model with optimal performance to establish an online predictive tool. The metabolism score developed in this study serves as an independent prognostic indicator for ESCC patients.

Efficacy and safety of androgen receptor inhibitors for treatment of advanced prostate cancer: A systematic review and network meta-analysis.

AIMS: Androgen receptor inhibitors (ARIs) have become an effective treatment for advanced prostate cancer (PC). However, it is unknown which ARI is the most helpful and safe for men with advanced PC. Our aim is to help physicians make clinical decisions and provide medication guidelines for patients with advanced PC to avoid potential risks when using ARIs for treatment. METHODS: We systematically searched the following databases: PubMed, Embase and Cochrane Library, with a literature publication deadline of February 2023. The primary efficacy outcomes were 18-month overall survival (OS), treatment-emergent adverse events (TEAEs), hypertension and fatigue. The network meta-analysis (NMA) was performed by Stata 15.1, and Revman 5.3 was used to assess the included studies' risk of bias. RESULTS: The analysis included 26 trials with 26 263 people. The surface under the cumulative ranking curve (SUCRA) concluded that enzalutamide (86.8%) showed the best effect in prolonging the OS of patients. Flutamide led to the highest risk of TEAEs (29.9%) and AEs leading to discontinuation (12.8%). Apalutamide (13.4%) led to the highest risk of grade ≥3 TEAEs. Enzalutamide had the highest risk of hypertension (0.2%), grade ≥3 hypertension (4.5%) and fatigue (5.2%). CONCLUSIONS: This NMA indicates there is no one ARI to reach both the most effective and safe therapy aims for treating advanced PC and that there is a compromise between the efficacy and safety of ARIs in the treatment of advanced PC. Physicians should weigh the risks to safety against the anticipated benefits when prescribing these drugs to patients with PC.

Fibrinogen-to-albumin ratio (FAR) is the best biomarker for the overall survival of patients with non-small-cell lung cancer.

Objective: The inflammatory response and the nutritional status are associated with overall survival (OS) in patients with non-small cell lung cancer (NSCLC), but it is unclear which biomarkers are better suited to predict prognosis. This study sought to determine which of the commonly existing inflammatory and nutritional indicators best predicted the OS. Methods: This study included 15 compound indicators based on inflammation or nutrition, with cutoff points obtained through the receiver operating characteristic (ROC) curve. Univariate and multivariate Cox proportional risk models were used to evaluate the relationship between these predictors and OS. Kaplan-Meier curves were used for survival analysis, and log-rank tests were used to compare differences between groups. The C-index was calculated to evaluate the predictive ability of the different indicators. Results: The study included 899 patients with NSCLC. In the univariate analysis, all 15 measures were significantly associated with the OS of patients (all p < 0.05). The results of the C-index analysis showed that the fibrinogen-to-albumin ratio (FAR), the systemic immune-inflammation index (SII), and the albumin-to-alkaline phosphatase ratio (AAPR) were the three indices with the best predictive performance. Among them, FAR (C-index = 0.639) had the best predictive power for OS in patients with NSCLC. In the different subgroups, FAR had the highest C-index in male, non-smoking, adenocarcinoma, and stage II patients. The C-index of the platelet-to-lymphocyte ratio (PLR) in female patients was the highest. SII was the highest in smokers, in those aged <65 and ≥65 years, and in stage III patients. The C-index of AAPR was the highest in non-adenocarcinomas. The C-index of the pan-immune-inflammation value (PIV) was the highest in stage I patients. In the multivariate Cox regression analysis, among FAR, SII, and AAPR, only FAR was an independent predictor of OS in patients with NSCLC. A high FAR was associated with a higher risk of death in patients with NSCLC (HR = 1.601, 95% CI = 1.028-2.495). In order to further evaluate the potential prognostic value of FAR, SII, and AAPR in patients with different stages, Cox regression analysis was performed for those with stage I-II and stage III NSCLC. The results showed that FAR was an independent prognostic factor for OS in patients with stage I-II NSCLC. Conclusion: For all patients with NSCLC, the prognostic power of FAR was superior to that of other inflammatory and nutritional indicators.

Long-term posttransplant survival outcome following bridging locoregional therapy in hepatocellular carcinoma patients: A systematic review and meta-analysis.

Aim: Liver transplantation (LT) is essential due to its curative efficacy, but liver-graft shortages have limited its widespread application. Bridging locoregional therapy (LRT) before LT has been performed to prevent tumor progression, and a recent literature review revealed that it is associated with a nonsignificant trend toward better survival outcomes. However, much more information on bridging therapy has become available since then. This meta-analysis aimed to compare the posttransplant survival and HCC recurrence between patients with and without pretransplant bridging LRT. Methods: Studies were identified in MEDLINE, SCOPUS, and the Cochrane Library. Two independent researchers screened titles and full articles, extracted relevant data, and conducted a parametric survival analysis. Results: Out of 4794 studies, 18 cohort studies were eligible. The 1-, 3-, and 5-year overall survival (OS) rates were 93.1%, 85.0%, and 79.1% for those in the bridging LRT group, while they were 91.8%, 81.1%, and 75.5% for those who did not receive LRT, respectively. There were no differences in overall survival between these groups (HR 0.90; 0.78-1.05, P = 0.17). Interestingly, we discovered that bridging therapy helped prolong survival significantly in a high-risk population with a long waiting time (HR 0.76; 0.60-0.96, P = 0.02). Unfortunately, bridging LRT did not improve disease-free survival (HR 0.98; 0.86-1.11, P = 0.70). Conclusions: The results indicate that bridging LRT does not generally change post-LT outcomes. However, bridging LRT can significantly improve survival in patients with a long waiting time for LT.

The role of biomarkers and dosimetry parameters in overall and progression free survival prediction for patients treated with personalized 90Y glass microspheres SIRT: a preliminary machine learning study.

BACKGROUND: Overall Survival (OS) and Progression-Free Survival (PFS) analyses are crucial metrics for evaluating the efficacy and impact of treatment. This study evaluated the role of clinical biomarkers and dosimetry parameters on survival outcomes of patients undergoing 90Y selective internal radiation therapy (SIRT). MATERIALS/METHODS: This preliminary and retrospective analysis included 17 patients with hepatocellular carcinoma (HCC) treated with 90Y SIRT. The patients underwent personalized treatment planning and voxel-wise dosimetry. After the procedure, the OS and PFS were evaluated. Three structures were delineated including tumoral liver (TL), normal perfused liver (NPL), and whole normal liver (WNL). 289 dose-volume constraints (DVCs) were extracted from dose-volume histograms of physical and biological effective dose (BED) maps calculated on 99mTc-MAA and 90Y SPECT/CT images. Subsequently, the DVCs and 16 clinical biomarkers were used as features for univariate and multivariate analysis. Cox proportional hazard ratio (HR) was employed for univariate analysis. HR and the concordance index (C-Index) were calculated for each feature. Using eight different strategies, a cross-combination of various models and feature selection (FS) methods was applied for multivariate analysis. The performance of each model was assessed using an averaged C-Index on a three-fold nested cross-validation framework. The Kaplan-Meier (KM) curve was employed for univariate and machine learning (ML) model performance assessment. RESULTS: The median OS was 11 months [95% CI: 8.5, 13.09], whereas the PFS was seven months [95% CI: 5.6, 10.98]. Univariate analysis demonstrated the presence of Ascites (HR: 9.2[1.8,47]) and the aim of SIRT (segmentectomy, lobectomy, palliative) (HR: 0.066 [0.0057, 0.78]), Aspartate aminotransferase (AST) level (HR:0.1 [0.012-0.86]), and MAA-Dose-V205(%)-TL (HR:8.5[1,72]) as predictors for OS. 90Y-derived parameters were associated with PFS but not with OS. MAA-Dose-V205(%)-WNL, MAA-BED-V400(%)-WNL with (HR:13 [1.5-120]) and 90Y-Dose-mean-TL, 90Y-D50-TL-Gy, 90Y-Dose-V205(%)-TL, 90Y-Dose- D50-TL-Gy, and 90Y-BED-V400(%)-TL (HR:15 [1.8-120]) were highly associated with PFS among dosimetry parameters. The highest C-index observed in multivariate analysis using ML was 0.94 ± 0.13 obtained from Variable Hunting-variable-importance (VH.VIMP) FS and Cox Proportional Hazard model predicting OS, using clinical features. However, the combination of VH. VIMP FS method with a Generalized Linear Model Network model predicting OS using Therapy strategy features outperformed the other models in terms of both C-index and stratification of KM curves (C-Index: 0.93 ± 0.14 and log-rank p-value of 0.023 for KM curve stratification). CONCLUSION: This preliminary study confirmed the role played by baseline clinical biomarkers and dosimetry parameters in predicting the treatment outcome, paving the way for the establishment of a dose-effect relationship. In addition, the feasibility of using ML along with these features was demonstrated as a helpful tool in the clinical management of patients, both prior to and following 90Y-SIRT.

Prognostic Role of Platelet-to-Lymphocyte and Neutrophil-to-Lymphocyte Ratios in Patients Irradiated for Glioblastoma Multiforme.

Background/Aim: Previous studies suggested pre-operative platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) to be predictive factors in patients with glioblastoma multiforme (GBM). This study investigated the prognostic role of PLR and NLR prior to or at the beginning of radiotherapy. Patients and Methods: In 80 patients with GBM receiving conventionally fractionated radiotherapy plus concurrent temozolomide following resection or biopsy, 12 factors including PLR and NLR were retrospectively evaluated regarding progression-free survival (PFS) and overall survival (OS). Results: On multivariable analyses, PLR ≤150, Karnofsky performance score (KPS) 90-100, and O6-methylguanine-DNA methyltransferase promoter methylation were significantly associated with improved PFS. Single lesion, KPS 90-100, and adjuvant chemotherapy were significantly associated with OS; PLR ≤150 showed a trend. NLR ≤3 showed a trend for associations with PFS and OS on univariable analyses. Conclusion: PLR prior to or at the beginning of radiotherapy was associated with treatment outcomes in patients irradiated for GBM and should be considered in future clinical trials.

Durvalumab supplementation for non-small-cell lung cancer: a meta-analysis study.

BACKGROUND: Durvalumab supplementation may have some potential in improving the efficacy in patients with non-small-cell lung cancer (NSCLC), and this meta-analysis aims to explore the impact of durvalumab supplementation on efficacy for NSCLC. METHODS: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the effect of durvalumab supplementation on efficacy in patients with NSCLC. Overall survival and progression-free survival were included for this meta-analysis. RESULTS: Four RCTs were finally included in the meta-analysis. Overall, compared with control group for NSCLC, durvalumab supplementation showed significantly improved survival rate (odd ratio [OR] = 1.64; 95% confidence interval [CI] = 1.31 to 2.06; P < 0.0001), overall survival ( hazard ratio [HR] = 0.73; 95% CI = 0.61 to 0.87; P = 0.0003), progression-free survival rate (OR = 2.31; 95% CI = 1.78 to 3.01; P < 0.00001) and progression-free survival (HR = 0.71; 95% CI = 0.54 to 0.95; P = 0.02), and had the capability to reduce the incidence of grade ≥ 3 adverse events (OR = 0.26; 95% CI = 0.16 to 0.42; P < 0.00001). CONCLUSIONS: Durvalumab supplementation is effective to improve the efficacy for NSCLC.

A comparison of clinical profile and treatment outcome of Hodgkin's Lymphoma in Tanzania according to HIV status during the HAART era.

BACKGROUND: The incidence of Hodgkin's lymphoma (HL) in people living with HIV (PLWHA) and on HAART is approximately 20-30 times higher than in HIV-negative individuals. Most patients with HIV-HL present at an advanced stage (III-IV) have 'B' symptoms and extranodal involvement. The natural history and risk stratification of HIV-HL has undergone a significant change as a result of HAART's rollout. This study investigated the differences in clinicopathological and survival patterns of HL among individuals with and without HIV disease in Tanzania during the HAART era. METHODOLOGY: This hospital-based retrospective cohort study was conducted at the ORCI, Dar-Es-Salaam, Tanzania. Chi-square and Fisher's exact tests were used to compare proportions. The student t-test was used to compare means. To determine factors that predict survival, we used the log-rank test to analyze the variables in univariate analysis. A Cox regression model was used to analyze the significant factors from univariate analysis in multivariate analysis. RESULTS: Eighty-three patients with HL were recruited, and the prevalence of HIV-positive status was 27.7%. Most of the patients with HIV-HL had an age of > 30 years (73.9%), while most of the non-HIV-HL patients had an age of ≤ 30 years (63.3%) (P = 0.02). The 2-year OS rate for HIV-HL was 34%, while that for non-HIV-HL was 67%. Among the HIV-HL patients, predictors of a poorer outcome were a CD4 count ≤ 200 cells/mm3 (P = 0.05), lack of HAART use (P = 0.00), and the use of HAART for ≤ 10 months (P = 0.00). CONCLUSION: The prevalence of HIV-HL was 27.7% among HL patients. HIV positivity is still a poor prognostic factor in our setting, especially for patients not on HAART, on HAART for ≤ 10 months, or with a low CD4 count below 200 cells/mm3. Patients with HIV-HL were older and had higher LDH levels, whereas patients with non-HIV-HL were younger and had low LDH levels.

Impact of Targeted Systemic Therapy and Radiotherapy on Patients Undergoing Spine Surgery for Metastatic Renal Cell Carcinoma.

BACKGROUND: In patients undergoing spine surgery for renal cell carcinoma (RCC), we sought to: (1) describe patterns of postoperative targeted systemic therapy and radiotherapy (RT), (2) compare perioperative outcomes among those treated with targeted systemic therapy to those without, and (3) evaluate the impact of targeted systemic therapy and/or RT on overall survival (OS) and local recurrence (LR). METHODS: A single-institution, retrospective cohort study of patients undergoing spine surgery for metastatic RCC from 2010 to 2021 was undertaken. Treatment groups were RT alone, targeted systemic therapy alone, dual therapy consisting of RT and targeted systemic therapy, and neither therapy. Multivariable Cox regression controlled for age, race, sex, insurance, and preoperative targeted systemic therapy. RESULTS: Forty-nine patients underwent spine surgery for RCC. Postoperatively, 4 patients (8%) received RT alone, 19 (38.8%) targeted systemic therapy alone, 12 (24.5%) dual therapy, and 13 (28.6%) neither. All groups were similar in demographics, preoperative Karnofsky Performance Score (P = 0.372), tumor size (P = 0.413), readmissions (P = 0.884), complications (P = 0.272), Karnofsky Performance Score (P = 0.466), and Modified McCormick Scale (P = 0.980) at last follow-up. Higher 1-year survival was found in dual therapy (83.3%) compared with other therapies. OS was significantly longer in patients with dual therapy compared with other therapies (log-rank; P = 0.010). Multivariate Cox regression (HR = 0.08, 95% CI = 0.02-0.31, P < 0.001) showed longer OS in dual therapy compared with other therapies. Seven patients (14.3%) experienced LR, and a similar time to LR was found between groups (log-rank; P = 0.190). CONCLUSION: In patients undergoing metastatic spine surgery for RCC, postoperative dual therapy demonstrated significantly higher 1-year survival and OS compared with other therapies. CLINICAL RELEVANCE: Multidisciplinary management of metastatic RCC is necessary to ensure timely implementation of targeted systemic therapy and RT to improve outcomes.

A Nomogram Based on Platelet Distribution Width-to-Lymphocyte Ratio to Predict Overall Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

Purpose: To evaluate the prognostic significance of platelet distribution width-to-lymphocyte ratio (PDWLR) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Moreover, a nomogram based on PDWLR was built and validated to predict the overall survival (OS) of this population. Patients and Methods: All LA-NPC patients who were diagnosed and treated between January 2015 and December 2017 at Guangxi Medical University Cancer Hospital were included. Cox regression analyses were performed to assess PDWLR and clinical features that might affect OS to screen for independent predictors. The independent predictors and important clinical variables were used to build and validate a nomogram for predicting OS. Then, the capability of the model was estimated by discrimination, calibration and clinical usefulness. Risk stratification was conducted using the nomogram-calculated risk score, and the comparison of survival in the high-risk group and the low-risk group was through Kaplan-Meier method. Results: This study included 746 LA-NPC patients. Multivariate Cox analysis suggested that age (hazard ratio [HR]: 1.81, 95% confidence interval [CI]: 1.18-2.78, P = 0.007), gender (HR: 2.03, 95% CI: 1.12-3.68, P = 0.019), pre-treatment plasma Epstein-Barr virus (EBV) DNA (HR: 1.55, 95% CI: 1.01-2.39, P = 0.047), PDWLR (HR: 2.61, 95% CI: 1.67-4.09, P < 0.001) were independent predictors of OS. Compared to the 8th edition TNM staging system, the nomogram based on the above four factors and important clinical variables (T stage and N stage) demonstrated better predictive performance. Moreover, the model had the ability to identify individuals at high risk. Conclusion: PDWLR was a promising negative predictor for patients with LA-NPC. The nomogram based on PDWLR demonstrated better predictive performance than the current staging system.

KIF2A correlates with lymphovascular invasion and higher tumor stage, and can be used to predict worse prognosis in patients with endometrial carcinoma.

Kinesin family protein 2A (KIF2A) is a microtubule depolymerase that participates in the progression of various cancers; however, its clinical utility in endometrial carcinoma (EC) remains unclear. The aim of the present study was to assess KIF2A expression and its relationship with prognosis in patients with EC. Data from 230 patients with EC who underwent tumor resection were reviewed in the current, retrospective study. KIF2A expression was measured in 230 formalin-fixed paraffin-embedded (FFPE) specimens of tumor tissue and 50 FFPE specimens of non-tumor tissue using immunohistochemistry (IHC). KIF2A expression was elevated in EC tumor tissue vs. non-tumor tissue (P<0.001). Furthermore, tumor KIF2A expression was linked with lymphovascular invasion (P=0.004) and higher International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.001). High tumor KIF2A expression (IHC score>3) was correlated with shorter disease-free survival (DFS; P=0.014) and overall survival (OS; P=0.012). Moreover, the time-dependent receiver operating characteristic curves revealed that tumor KIF2A expression had an acceptable use for estimating the relapse and death risks at each timepoint within 6 years, with each area under the curve remaining stable at ≥0.7. Notably, tumor KIF2A expression (high vs. low) independently forecast shorter DFS (hazard ratio, 2.506; P=0.013), but not OS (P>0.05). Furthermore, information from The Human Protein Atlas database indicated that high tumor KIF2A expression was associated with worse OS in patients with EC (P=0.027). Tumor KIF2A is not only associated with lymphovascular invasion and higher FIGO stage, but also reflects unfavorable survival in patients with EC.

Early discontinuation of immune checkpoint inhibitor therapy prior to disease progression in patients with metastatic non-small cell lung cancer: a survival analysis.

Introduction: Limited survival data are available for patients with metastatic non-small cell lung cancer (mNSCLC) who stop immune checkpoint inhibitor therapy (ICI) early for reasons other than progression of disease (POD), such as immune-related adverse events (irAEs). Methods: We conducted a retrospective observational study of all patients with mNSCLC treated with ICIs, with or without combination chemotherapy, at 3 Mayo Clinic sites between 2011 and 2022. Separate analyses were conducted at 6- and 12-month intervals. Patients who discontinued ICI due to POD prior to these time points were excluded from the analysis. Results: A total of 246 patients with stage IV NSCLC used ICIs. Patients were then excluded if they had experienced POD prior to 6 or 12 months, resulting in 81 and 63 patients, respectively, for each timepoint. Sixty-four patients continued treatment beyond 6 months and were found to have longer progression-free survival (PFS) compared to the 17 patients who discontinued treatment (22.8 months vs 11.8 months, P =1.1E-04), as well as a significant increase in overall survival (OS) (33.9 months vs 14.4 months, P =7.2E-08). Forty patients continued treatment beyond 12 months and had longer PFS compared to the 23 patients that discontinued treatment (27.9 months vs 14.8 months, P =1.1E-04), as well as a significant increase in OS (39.7 months vs 18.0 months, P =2.0E-07). The most common reason for ICI discontinuation was irAEs. Other common reasons for stopping ICI were non-irAEs and stable disease. At both time points, 12 patients continued or restarted ICI after experiencing an irAE, and 2 patients experienced recurrent/new grade 1-2 irAEs. More patients continued/rechallenged with ICI after experiencing an irAE in the groups that continued ICI compared to those that discontinued ICI. Conclusions: Patients with mNSCLC and no POD who continued ICI beyond 6 months and 12 months, experienced significantly increased PFS and OS compared to patients who discontinued ICI, with larger increases in those who continued ICI past 12 months. Oncology providers should discuss the survival benefits of continuing ICI and offer support to overcome obstacles to continuation of treatment, if possible, particularly management of grade 1 and 2 irAEs.