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.

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.

The effect of ileal resection length on postoperative complications and prognosis in right colon cancer.

BACKGROUND: There is a lack of literature on the length of the terminal ileum to be resected in right hemicolectomy for colon cancer. Therefore, we aimed to determine the mean ileal loop length and the effect of this variation on postoperative complications and long-term oncological outcomes in patients who underwent right hemicolectomy. METHODS: Right hemicolectomy surgeries performed for colon cancer in a tertiary care hospital between January 2011 and December 2018 were retrospectively analyzed from a prospective database. Two patient groups were established based on the mean length of the resected ileum above and below 7 cm. The two groups were compared for clinicopathological data, postoperative complications, mortality, long-term overall survival (OS) and disease-free survival (DFS). The factors contributing to OS and DFS were analyzed. RESULTS: The study included 217 patients. Body mass index (BMI) values were significantly higher in the ileum resection length > 7 cm group (p = 0.009). Pathological N stage, tumor diameter, and number of metastatic lymph nodes were significantly higher in the ileum resection length > 7 cm group (p = 0.001, p = 0.001, and p = 0.026, respectively). There was no significant difference for postoperative complication and mortality rates between the two groups. The mean follow-up period was 61.2 months (2-120) in all patients. The total number of deaths was 29 (11.7%) while the 60-month OS was 83.5% and 50-month DFS was 81.8%. There was no significant difference between the groups in terms of OS and DFS rates (p > 0.05). CONCLUSIONS: Excessive resection of the distal ileum in right hemicolectomy does not provide any benefit in terms of prognosis and complications.The ileum resection length and values close to it in our study appear to be sufficient.

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.

BSG Isoform 2 (ENST00000353555) Is a Prognostic Biomarker in Predicting Unfavorable Overall Survival of Patients With Liver Hepatocellular Carcinoma.

BACKGROUND: CD147, encoded by the BSGgene, has complex transcripts that encode proteins of different lengths. Total BSG transcription is a prognostic biomarker for patients with liver cancer. This study tried to analyze the expression profile and prognostic significance of BSG transcripts in liver cancer. MATERIALS AND METHODS: RNA sequencing data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project, survival data from TCGA, and protein expression data from the Human Protein Atlas were systematically analyzed. RESULTS: Among the four protein-coding transcripts of BSG, ENST00000353555 encoding basigin-2 is the dominant transcript isoform. It might be an independent prognostic biomarker for unfavorable overall survival in patients with liver cancer (HR: 1.404, 95% CI: 1.1224-1.754, p = 0.003). CONCLUSIONS: ENST00000353555 might be a prognostic biomarker linking unfavorable overall survival in liver cancer patients.

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.

Lenvatinib radiofrequency ablation sequential therapy offers survival benefits for patients with unresectable hepatocellular carcinoma at intermediate stage and the liver reserve of Child-Pugh A category: A multicenter study.

AIM: This study aims to evaluate the efficacy and safety of lenvatinib radiofrequency ablation (RFA) sequential therapy for certain hepatocellular carcinoma (HCC) patients. METHODS: One hundred and nineteen patients with unresectable HCC in the intermediate stage with Child-Pugh A were retrospectively recruited in a multicenter setting. Those in the lenvatinib RFA sequential therapy group received lenvatinib initially, followed by RFA and the retreatment with lenvatinib. The study compared overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) between patients undergoing sequential therapy and lenvatinib monotherapy. RESULTS: After propensity score matching, 25 patients on sequential therapy and 50 on monotherapy were evaluated. Independent factors influencing OS were identified as sequential therapy, modified albumin-bilirubin (mALBI) grade, and relative dose intensity (%) with hazard ratios (HRs) of 0.381 (95% confidence interval [CI], 0.186-0.782), 2.220 (95% CI, 1.410-3.493), and 0.982 (95% CI, 0.966-0.999), respectively. Stratified analysis based on mALBI grades confirmed the independent influence of treatment strategy across all mALBI grades for OS (HR, 0.376; 95% CI, 0.176-0.804). Furthermore, sequential therapy was identified as an independent factor of PFS (HR, 0.382; 95% CI, 0.215-0.678). Sequential therapy significantly outperformed monotherapy on survival benefits (OS: 38.27 vs. 18.96 months for sequential therapy and monotherapy, respectively, p = 0.004; PFS: 13.80 vs. 5.32 months for sequential therapy and monotherapy, respectively, p < 0.001). Sequential therapy was significantly associated with complete response by modified Response Evaluation Criteria in Solid Tumors (odds ratio, 63.089). Ten of 119 patients experienced grade 3 AEs, with no AE beyond grade 3 observed. CONCLUSION: Lenvatinib RFA sequential therapy might offer favorable tolerability and potential prognostic improvement compared to lenvatinib monotherapy.

R2-ISS staging combined with circulating plasma cells improves risk stratification for newly diagnosed multiple myeloma: a single-center real-world study.

We aimed to evaluate if circulating plasma cells (CPC) detected by flow cytometry could add prognostic value of R2-ISS staging. We collected the electronic medical records of 336 newly diagnosed MM patients (NDMM) in our hospital from January 2017 to June 2023. The median overall survival (OS) for patients and R2-ISS stage I-IV were not reached (NR), NR, 58 months and 53 months, respectively. There was no significant difference in OS between patients with stage I and patients with stage II (P = 0.309) or between patients with stage III and patients with stage IV (P = 0.391). All the cases were re-classified according to R2-ISS stage and CPC numbers ≥ 0.05% (CPC high) or<0.05% (CPC low) into four new risk groups: Group 1: R2-ISS stage I + R2-ISS stage II and CPC low, Group 2: R2-ISS stage II and CPC high + R2-ISS stage III and CPC low, Group 3: R2-ISS stage III and CPC high + R2-ISS stage IV and CPC low, Group 4: R2-ISS stage IV and CPC high. The median OS were NR, NR, 57 months and 32 months. OS of Group 1 was significantly longer than that of Group 2 (P = 0.033). OS in Group 2 was significantly longer than that of Group 3 (P = 0.007). OS in Group 3 was significantly longer than that of Group 4 (P = 0.041). R2-ISS staging combined with CPC can improve risk stratification for NDMM patients.

Contemporary survival in metastatic bladder cancer patients: A population-based study.

The overall survival (OS) improvement after the advent of several novel systemic therapies, designed for treatment of metastatic urothelial carcinoma of the urinary bladder (mUCUB), is not conclusively studied in either contemporary UCUB patients and/or non-UCUB patients. Within the Surveillance, Epidemiology, and End Results database, contemporary (2017-2020) and historical (2000-2016) systemic therapy-exposed metastatic UCUB and, subsequently, non-UCUB patients were identified. Separate Kaplan-Meier and multivariable Cox regression (CRM) analyses first addressed OS in mUCUB and, subsequently, in metastatic non-UCUB (mn-UCUB). Of 3443 systemic therapy-exposed patients, 2725 (79%) harbored mUCUB versus 709 (21%) harbored mn-UCUB. Of 2725 mUCUB patients, 582 (21%) were contemporary (2017-2020) versus 2143 (79%) were historical (2000-2016). In mUCUB, median OS was 11 months in contemporary versus 8 months in historical patients (Δ = 3 months; p < .0001). After multivariable CRM, contemporary membership status (2017-2020) independently predicted lower overall mortality (OM; hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.60-0.76; p < .001). Of 709 mn-UCUB patients, 167 (24%) were contemporary (2017-2020) and 542 (76%) were historical (2000-2016). In mn-UCUB, median OS was 8 months in contemporary versus 7 months in historical patients (Δ = 1 month; p = .034). After multivariable CRM, contemporary membership status (2017-2020) was associated with HR of 0.81 (95% CI = 0.66-1.01; p = .06). In conclusion, contemporary systemic therapy-exposed metastatic patients exhibited better OS in UCUB. However, the magnitude of survival benefit was threefold higher in mUCUB and approximated the survival benefits recorded in prospective randomized trials of novel systemic therapies.

Novel genetic alterations in liver cancer distinguish distinct clinical outcomes and combination immunotherapy responses.

Introduction: Genomic profiling has revolutionized therapeutic interventions and the clinical management of liver cancer. However, pathogenetic mechanisms, molecular determinants of recurrence, and predictive biomarkers for first-line treatment (anti-PD-(L)1 plus bevacizumab) in liver cancer remain incompletely understood. Materials and methods: Targeted next-generation sequencing (tNGS) (a 603-cancer-gene panel) was applied for the genomic profiling of 232 hepatocellular carcinoma (HCC) and 22 intrahepatic cholangiocarcinoma (ICC) patients, among which 47 unresectable/metastatic HCC patients underwent anti-PD-1 plus bevacizumab therapy. Genomic alterations were estimated for their association with vascular invasion (VI), location of onset, recurrence, overall survival (OS), recurrence-free survival (RFS), and anti-PD-1 plus bevacizumab therapy response. Results: The genomic landscape exhibited that the most commonly altered genes in HCC were TP53, FAT3, PDE4DIP, KMT2C, FAT1, and MYO18A, while TP53, FAT1, FAT3, PDE4DIP, ROS1, and GALNT11 were frequently altered in ICC; notably, KRAS (18.18% vs. 1.29%) and BAP1 (13.64% vs. 1.29%) alterations were significantly more prevalent in ICC. Comparison analysis demonstrated the distinct clinicopathological/genomic characterizations between Chinese and Western HCC cohorts. Genomic profiling of HCC underlying VI showed that LDLR, MSH2, KDM5D, PDE3A, and FOXO1 were frequently altered in the VI group compared to patients without VIs. Compared to the right hepatic lobes of HCC patients, the left hepatic lobe of HCC patients had superior OS (median OS: 36.77 months vs. unreached, p < 0.05). By further comparison, Notch signaling pathway-related alterations were significantly prevalent among the right hepatic lobes of HCC patients. Of note, multivariate Cox regression analysis showed that altered RB1, NOTCH3, MGA, SYNE1, and ZFHX3, as independent prognostic factors, were significantly correlated with the OS of HCC patients. Furthermore, altered LATS1 was abundantly enriched in the HCC-recurrent group, and impressively, it was independent of clinicopathological features in predicting RFS (median RFS of altered type vs. wild-type: 5.57 months vs. 22.47 months, p < 0.01). Regarding those treated HCC patients, TMB value, altered PTPRZ1, and cell cycle-related alterations were identified to be positively associated with the objective response rate (ORR), but KMT2D alterations were negatively correlated with ORR. In addition, altered KMT2D and cell cycle signaling were significantly associated with reduced and increased time to progression-free survival (PFS), respectively. Conclusion: Comprehensive genomic profiling deciphered distinct molecular characterizations underlying VI, location of onset, recurrence, and survival time in liver cancer. The identification of novel genetic predictors of response to anti-PD-1 plus bevacizumab in HCC facilitated the development of an evidence-based approach to therapy.

Comparative efficacy of Bacillus Calmette-Guérin instillation and radical cystectomy treatments for high-risk non-muscle-invasive urothelial cancer classified as high-grade T1 in initial and repeat transurethral resection of bladder tumor.

Objective: To compare the differential therapeutic effects of Bacillus Calmette-Guérin (BCG) instillation and radical cystectomy (RC) for high-risk non-muscle-invasive urothelial cancer (NMIBC) classified as high-grade T1 in initial and repeat transurethral resection of bladder tumors (TURBT) and to construct a prediction model. Methods: We retrospectively analyzed the clinical data of patients with malignant bladder tumors treated at the First Affiliated Hospital of Soochow University from January 2016 to December 2017 and compared the differences in 1-year, 2-year, 3-year, 5-year, and comprehensive overall survival (OS) and progression-free survival (PFS) between BCG instillation treatment and RC treatment. Survival curves were drawn to show differences in OS and PFS between the two groups. Concurrently, univariate and multivariate COX analyses were performed to identify risk factors affecting OS and PFS, and a nomogram was created. Results: In total, 146 patients were included in the study, of whom 97 and 49 were in the BCG and RC groups, respectively. No statistical differences were observed in the 1- and 2-year OS and PFS between the two groups, whereas significant statistical differences were found in the 3-year, 5-year, and comprehensive OS and PFS. Survival curves also confirmed the statistical differences in OS and PFS between the BCG and RC groups. Multivariate COX analysis revealed that the treatment method, concomitant satellite lesions, and albumin-to-alkaline phosphatase ratio (AAPR) were independent risk factors affecting OS and PFS. The nomogram that was further plotted showed good predictive ability for OS and PFS. Conclusion: For patients who exhibit high-level T1 pathology after both initial and repeat TURBT, especially those with low AAPR, and concomitant satellite lesions, choosing RC as a treatment method offers a better prognosis.

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.

Values of a novel comprehensive prognostic nutritional index (FIDA) in the prognosis of non-small cell lung cancer.

Background: This study focuses on determining the prognostic and predictive value of the comprehensive prognostic nutrition index (FIDA) in individuals undergoing treatment for Non-Small-Cell Lung Carcinoma (NSCLC). Methods: This retrospective analysis encompassed 474 of NSCLC patients treated from January 2010 through December 2019. Employing the Lasso-COX regression approach, eight blood parameters were identified as significant prognostic indicators. These parameters contributed to the formulation of the comprehensive prognostic nutrition index FIDA. Utilizing X-tile software, the patient cohort was categorized into either a high or low FIDA group based on an established optimal threshold. The cohort was then randomly segmented into a training set and a validation set using SPSS software. Subsequent steps involved conducting univariate and multivariate regression analyze to develop a prognostic nomogram. The effectiveness of this nomogram was evaluated by calculating the AUC. Results: Analysis of survival curves for both the training and validation sets revealed a poorer prognosis in the high FIDA group compared to the low FIDA group. This trend persisted across various subgroups, including gender, age, and smoking history, with a statistical significance (p<0.05). Time-dependent ROC and diagnostic ROC analyses affirmed that FIDA serves as an effective diagnostic and prognostic marker in NSCLC. Moreover, Cox regression multivariate analysis established FIDA as an independent prognostic factor for NSCLC. The prognostic nomogram, integrating FIDA and clinical data, demonstrated substantial prognostic utility and outperformed the traditional TNM staging systemin predicting overall survival (OS). Conclusion: FIDA emerges as a dependable predictor of outcomes for patients with NSCLC. It offers a practical, cost-effective tool for prognostication in regular clinical applications.

Chemotherapy related changes in cfDNA levels in squamous non-small cell lung cancer: correlation with symptom scores and radiological responses.

Aim: There is limited data on prognostic value of baseline plasma cell free DNA (cfDNA) in advanced squamous non-small cell lung cancer (sq-NSCLC). This prospective observational study aimed to assess change in plasma cfDNA levels in locally-advanced/metastatic sq-NSCLC with chemotherapy and its correlation with symptom-scores and radiological-responses. Methods: Chemotherapy-naive patients with stages-IIIB/IIIC/IV sq-NSCLC (n = 59), smokers with chronic obstructive pulmonary disease [COPD, COPD-controls (CC); n = 27] and healthy-controls (n = 25) were enrolled. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from mean visual-analog-scores (VAS) of dyspnoea, cough, chest pain, hemoptysis RSB, anorexia and fatigue (all six for TSB). cfDNA was isolated from peripheral blood. All patients received platinum-doublet chemotherapy. RSB/TSB/cfDNA assessment and contrast-enhanced computed tomography (CECT)-thorax scans were done at baseline and post-chemotherapy. Results: At baseline, 13/59 (22%) sq-NSCLC, 3/27 (11%) CC and none (0%) healthy-controls had detectable cfDNA. All three CC were heavy smokers with no evidence of malignancy and undetectable cfDNA levels on repeat testing. In sq-NSCLC group, majority were males (95%), current-smokers (88%), heavy-smokers (70%), had metastatic disease (59%) with median age of 65 years. Eastern Co-operative Oncology Group (ECOG) performance status (PS) was 0-1 (56%) and 2 (42%). Median RSB- and TSB-scores were 9 [interquartile range (IQR) = 5-14] and 16 (IQR = 9-23), respectively. Of the 59 patients, 54 received ≥ 1 cycle while 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/27 (66.7%). No baseline characteristic correlated with cfDNA detectability. Median overall survival (OS) and progression-free survival (PFS) were 262 days and 167 days, respectively. ECOG PS ≥ 2, RSB-score > 9 and TSB-score > 16 were all associated with worse OS and PFS as was cfDNA detectability [median OS = 97 days vs. 298 days and median PFS = 97 days vs. 197 days; P = 0.025; hazard ratio (HR) = 2.17]. Conclusions: Baseline cfDNA detectability is independently associated with poor OS and PFS in patients with advanced sq-NSCLC on chemotherapy.

Periodontitis is an immune-related adverse event associated with immune checkpoint inhibitors: A multi-center cohort study.

Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs) across various organ systems including oral health complications such as dry mouth and stomatitis. In this study, we aimed to determine the risk of periodontitis among patients on immune checkpoint inhibitors (ICIs) and to test the associations between ICI-associated periodontitis and other immune-related adverse events (irAEs). We performed a retrospective cohort study involving adult cancer patients between January 2010 and November 2021. Patients on an ICI were propensity score-matched to patients not on an ICI. The primary outcome was the occurrence of periodontitis. ICIs included programmed cell death 1 (PD-1) inhibitors programmed cell death ligand 1 (PD-L1) inhibitors, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors. The risk of periodontitis following ICI use was derived through a Cox proportional hazard model and Kaplan-Meier survival analysis. Overall, 868 patients on an ICI were matched to patients not on an ICI. Among the ICI cohort, 41 (4.7%) patients developed periodontitis. The incidence rate of periodontitis was significantly higher in patients on an ICI than in patients not on an ICI (55.3 vs 25.8 per 100 patient-years, incidence rate ratio=2.14, 95% CI=1.38-3.33). Both the use of PD-L1 inhibitors (multivariate HR=2.5, 95%CI=1.3-4.7) and PD-1 inhibitors (multivariate HR=2.0, 95%CI=1.2-3.2) were associated with the risk of periodontitis. The presence of immune-related periodontitis was associated with better overall survival (not reached vs 17 months, log-rank p-value<0.001), progression-free survival (14.9 vs 5.6 months, log-rank p-value=0.01), and other concomitant immune-related cutaneous adverse events. In conclusion, ICI was associated with an increased risk of periodontitis. Immune-related periodontitis as an irAE was associated with better cancer survival and concomitant cutaneous irAEs.