Optimal Management for Primary High Grade Ta Bladder Cancer: Role of re-staging TURBT and Intravesical Adjuvant Therapy.

Objective: This study aims to investigate the impact of risk group classification, restaging transurethral resection (re-TURBT), and adjuvant treatment intensity on recurrence and progression risks in high-grade Ta tumours in patients with non-muscle invasive bladder cancer (NMIBC). Materials and methods: Data from a comprehensive bladder cancer database were utilized for this study. Patients with primary high-grade Ta tumours were included. Risk groups were classified according to AUA/SUO criteria. Tumour characteristics and patient demographics were analysed using descriptive statistics. Cox proportional hazard regression models were used to assess the effect of re-TURBT and other clinical/treatment-related predictors on recurrence- and progression-free survivals. The survivals by selected predictors were estimated using Kaplan-Meier method, and groups were compared by the log-rank test. Results: Among 218 patients with high-grade Ta bladder cancer, those who underwent re-TURBT had significantly better 5-year recurrence-free survival (71.1% vs. 26.8%, p = 0.0009) and progression-free survival (98.6% vs. 73%, p = 0.0018) compared with those with initial TURBT alone. Full BCG treatment (induction and maintenance) showed lower recurrence risk, especially in high-risk patients. However, residual disease at re-TURBT did not significantly affect recurrence risk. Conclusions: This study highlights the significance of risk group classification, the role of re-TURBT, and the intensity of adjuvant treatment in the management of high-grade Ta tumours. A risk-adapted model is crucial to reduce the burden of unnecessary intravesical treatment and endoscopic procedures.

Relationships between postoperative recurrences and standardized uptake value on 18F-fluorodeoxyglucose-positron emission tomography in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma who underwent curative pancreatic resection after neoadjuvant chemoradiotherapy.

BACKGROUND: This study aimed to examine postoperative recurrence after curative pancreatic resection following neoadjuvant chemoradiotherapy (NACRT) in patients with resectable (R-) and borderline resectable (BR-) pancreatic ductal adenocarcinoma (PDAC), focusing on its relationship with the standardized uptake value (SUV) on 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). METHOD: The postoperative initial recurrence patterns were examined in patients with R- and BR-PDAC who underwent NACRT followed by curative pancreatic resection. Data collected from three prospective clinical trials were retrospectively analysed. RESULTS: After a median follow-up of 29 months, 91 (60 %) of 151 patients experienced postoperative recurrence. The median recurrence-free survival (RFS) for all patients was 18 months. The sites of first recurrence were lung-only in 24 (26 %) patients, liver-only in 23 (25 %), local-only in 11 (12 %), peritoneum-only in 10 (11 %), other single site in 5 (5 %), and multiple sites in 19 (21 %) patients. Multivariate analysis identified the maximum standardized uptake value (SUVmax) on FDG-PET at diagnoses ≥5.40 (hazard ratio [HR], 1.62; 95 % confidence interval [CI], 1.01-2.61; p = 0.045) and node-positive pathology (HR, 2.01; 95 % CI, 1.32-3.08; p = 0.001) as significant predictors of RFS. Furthermore, the SUVmax at initial diagnosis and after NACRT correlated with liver metastasis. CONCLUSION: R- and BR-PDACs with high SUV on FDG-PET at diagnosis are risk factors for postoperative recurrence. Among patients who undergo surgery after NACRT, those with a high SUVmax at diagnosis or post-NACRT require careful attention for postoperative liver recurrence.

Tenofovir Is Associated With a Better Prognosis Than Entecavir for Hepatitis B Virus-Related Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Whether tenofovir or entecavir has different effects on the prevention of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in secondary and tertiary preventive settings is still a matter of debate. This study aimed to compare the long-term prognosis of HCC between tenofovir and entecavir in patients with chronic hepatitis B. METHODS: Chronic hepatitis B patients diagnosed with HCC between November 2008 and December 2018 and treated with either entecavir or tenofovir at a tertiary center in Korea were included. The effect of tenofovir compared with entecavir on the prognosis of HBV-related HCC was assessed using multivariable-adjusted Cox and propensity score (PS)-matched analyses. Various predefined subgroup analyses were conducted. RESULTS: During a median follow-up period of 3.0 years, the mortality rate for entecavir-treated patients (n = 3469) was 41.2%, while tenofovir-treated patients (n = 3056) had a mortality rate of 34.6%. Overall survival (OS) was better in the tenofovir group (adjusted hazard ratio [aHR], 0.79; P < .001), which were consistently observed in the PS-matched analysis. The magnitude of the risk difference in OS was more prominent 2 years after the diagnosis of HCC (aHR, 0.50; P < .001) than 2 years before (aHR, 0.88; P = .005), and it was more pronounced in patients with earlier HCC stages. In all subgroups, except for those with shorter life expectancy, such as those with compromised liver function, tenofovir was associated with better OS compared with entecavir. CONCLUSIONS: Among patients with HBV-related HCC, those treated with tenofovir had a better prognosis than those treated with entecavir, particularly among those with prolonged survival.

Exploring metastasis and recurrence patterns in low-risk grade 3 endometrial cancer: A multicenter retrospective cohort study.

OBJECTIVE: Females with low-risk endometrial cancer typically have low lymph node metastasis risk and promising prognosis without lymphadenectomy. However, the impact of grade 3 endometrial cancer on nodal involvement, recurrence, and prognosis within this specific subgroup remains unclear. Therefore, in this study, we aimed to investigate the prognosis, patterns of metastasis, and recurrence in a subgroup of females with grade 3 early-stage low-risk endometrioid endometrial cancer. METHODS: We identified patients from the endometrial cancer cohorts of seven institutional hospitals. The study included patients who underwent hysterectomy between January 2013 and December 2021 with preoperative endometrioid histological type, less than half myometrial invasion, no tumor spread outside the corpus on imaging, normal CA-125 level, and histological grade 3. The clinicopathological characteristics and survival outcomes of the patients were collected. Recurrence-free survival was estimated using the Kaplan-Meier method and compared using the log rank test. RESULTS: Overall, 36 patients were included in this analysis. Of the 33 patients who underwent lymphadenectomy, 1 (1/33, 3.0 %) had lymph node metastasis and 27 (75.0 %) received adjuvant therapy. At a median follow-up of 58 months, three females (8 %) had recurrence and all cases involved lymph nodes. The 5-year recurrence-free survival was 88.7 %. No significant difference was observed in the recurrence-free survival between females who did and did not undergo lymphadenectomy (p = 0.554). CONCLUSION: Females diagnosed with low-risk grade 3 endometrial cancer typically have favorable prognosis. However, lymph node metastasis and recurrence risks still exist, with all recorded instances of recurrence involving lymph nodes.

Inflammation and Colorectal Cancer: A Meta-Analysis of the Prognostic Significance of the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI).

The overall prognosis for colorectal cancer (CRC) remains challenging as the survival time varies widely, even in patients with the same stage of disease. Recent studies suggest prognostic relevance of the novel markers of systemic inflammation, the systemic immune-inflammation index (SII), and the systemic inflammation response index (SIRI). We conducted a comprehensive meta-analysis to assess the prognostic significance of the SII and the SIRI in CRC. We searched the relevant literature for observational studies, and random effects models were employed to conduct a statistical analysis using the metaanalysisonline.com platform. Pooled effect sizes were reported with hazard ratios (HRs) and corresponding 95% confidence intervals (CI). Data from 29 studies published between 2016 and 2024, comprising 10,091 participants, were included in our meta-analysis on SII. CRC patients with high SII levels had worse disease outcomes, which were associated with poor OS (HR: 1.75; 95% CI: 1.4-2.19) and poor PFS/DFS/RFS (HR: 1.25; 95% CI: 1.18-1.33). This increased risk of worse OS was present irrespective of the treatment strategy, sample size (<220 and ≥220), and cutoff used to define high and low SII (<550 and ≥550) groups. Based on data from five studies comprising 2362 participants, we found a strong association between the high SIRI and worse OS (HR: 2.65; 95% CI: 1.6-4.38) and DFS/RFS (HR: 2.04; 95% CI: 1.42-2.93). According to our results, both the SII and SIRI hold great promise as prognostic markers in CRC. Further validations are needed for their age- and stage-specific utility in the clinical routine.

Prognostic significance of invasive cribriform gland size and percentage in Gleason score 7 prostate adenocarcinoma.

OBJECTIVES: Cribriform glands are linked to poorer outcomes in prostate adenocarcinoma. We aimed to assess the prognostic role of the percentage of cribriform glands and the size of the largest invasive cribriform gland in Gleason score 7 prostate adenocarcinomas. METHODS: The presence, percentage, and size of the invasive cribriform glands were investigated and their association with prognostic factors were assessed in 177 Grade Groups 2 and 3 prostate adenocarcinomas. RESULTS: Biochemical recurrence-free survival was statistically significantly lower in cases with a cribriform gland percentage greater than 10% (P < .001) and in cases where the largest invasive cribriform gland size was greater than 0.5 mm (P < .001). Mean largest cribriform gland size and percentage were statistically significant associated with more advanced pT status, lymph node metastasis, biochemical recurrence, and higher preoperative prostate-specific antigen values. CONCLUSIONS: Our findings suggest that the presence of a cribriform pattern, increases in the percentage of such patterns, and increases in the size of the largest cribriform gland within a given tumor are associated with poor prognosis. We suggest that a more aggressive clinical approach may be needed in Grade Group 2 and 3 cases with invasive cribriform glands larger than 0.5 mm and a cribriform gland percentage greater than 10%, especially in prostate needle biopsy specimens.

Primary treatments for solitary hepatocellular carcinoma ≤ 3 cm: A systematic review and network meta-analysis.

Various treatment modalities are available for small solitary hepatocellular carcinoma (HCC), yet the optimal primary treatment strategy for tumors ≤ 3 cm remains unclear. This network meta-analysis investigates the comparative efficacy of various interventions on the long-term outcomes of patients with solitary HCC ≤ 3 cm. A systematic search of electronic databases from January 2000 to December 2023 was conducted to identify studies that compared at least two of the following treatments: surgical resection (SR), radiofrequency ablation (RFA), microwave ablation (MWA), and transarterial chemoembolization (TACE). Survival data were extracted, and pooled hazard ratios with 95% confidence intervals were calculated using a frequentist network meta-analysis. A total of 30 studies, comprising 2 randomized controlled trials and 28 retrospective studies, involving 8,053 patients were analyzed. Surgical resection showed the highest overall survival benefit with a p-score of 0.95, followed by RFA at 0.59, MWA at 0.23, and TACE, also at 0.23. Moreover, SR provided the most significant recurrence-free survival advantage, with a p-score of 0.95, followed by RFA at 0.31 and MWA at 0.19. Sensitivity analyses, excluding low-quality or retrospective non-matched studies, corroborated these findings. This network meta-analysis demonstrates that SR is the most effective first-line curative treatment for single HCC ≤ 3 cm, followed by RFA in patients with preserved liver function. The limited data on MWA and TACE underscore the need for further studies.

Adjuvant Therapy for High-Risk Stage II Melanoma: Current Paradigms in Management and Future Directions.

Melanoma is the fifth most common cancer in the United States and accounts for the majority of all skin cancer-related deaths, making it the most lethal cutaneous malignancy. Systemic adjuvant therapy for stage IIB-IV melanoma is now approved for patients who have undergone surgical resection, given the appreciable risk of recurrence and mortality in this patient population. Despite the lower stage, high-risk stage II melanoma (stage IIB/IIC) can often exhibit an even more aggressive course when compared to stage IIIA/IIIB disease, thus justifying consideration of adjuvant therapy in these patients. In this review, we highlight the current standard of practice for the treatment of stage IIB/C melanoma, with a focus on adjuvant therapies supported by published landmark clinical trials, including anti-PD-1 therapy. Notably, adjuvant therapies approved thus far in this patient population have demonstrated an improvement in recurrence-free survival, while their impact on overall survival is pending. Finally, this review highlights currently ongoing trials and future directions for research and treatment possibilities for high-risk clinical stage II melanoma.

The conditional recurrence-free survival after R0 hepatectomy for locally advanced intrahepatic cholangiocarcinoma: A competing risk analysis based on inflammation-nutritional status.

Background: Conditional survival analysis can serve as a dynamic prognostic metric, which helps to estimate the real-time survival probability over time. The present study conducted a conditional recurrence-free survival (CRFS) analysis for locally advanced intrahepatic cholangiocarcinoma (ICC) after R0 hepatectomy from an inflammatory-nutritional perspective using the competing risk method. Methods: We extracted the medical data of 164 locally advanced ICC patients after R0 resection from Sun Yat-sen University Cancer Center. The calculation formula of the CRFS rate is CRFS(y/x) = RFS(y + x)/RFS(x). Univariable and multivariable COX regression analysis and competing risk analysis were conducted to identify RFS indicators. Results: Considering death before recurrence as a competing risk factor, the conditional RFS rates every 6 months gradually increased over time. The 24-month RFS rate increased from 29.2 % to 49.9 %, 68.5 %, and 85.1 % given 6, 12, and 18-month already recurrence-free survival, respectively. Both in multivariate COX regression analysis and competing risk analysis, tumor diameter and number, lymph node metastasis, aggregate systemic inflammation index score (AISI), and albumin-bilirubin score (ALBI) all remained significant. For both AISI and ALBI variables, the CRFS rates in the low-value set were higher than those of the high-value set. Conclusions: Conditional RFS rates of locally advanced ICC after R0 hepatectomy dynamically increased over time, which contributed to reducing survivors' psychological distress and facilitating personalized follow-up schedules. In addition, a person's inflammatory and nutritional status significantly impact the recurrence risk. Oncologists should consider the role of inflammation-nutritional status when making decisions for patients with locally advanced ICC.

Mitomycin C vs. Bacillus Calmette-Guerin for treatment of intermediate-risk nonmuscle invasive bladder cancer patients-A comparative analysis from a single center.

BACKGROUND: Induction followed by 1 year maintenance instillation of intravesical Bacillus Calmette-Guerin (BCG) is the standard treatment for intermediate-risk (IR) nonmuscle invasive bladder cancer (NMIBC) patients. Few data exist on the efficacy of Mitomycin C (MMC) instillation in this setting. METHODS: We retrospectively analyzed 226 IR-NMIBC patients classified by the International Bladder Cancer Group (IBCG) and 250 IR-NMIBC intravescical treatment-naïve patients classified by the European Association of Urology (EAU). All patients received either a full induction course of BCG or 40 mg/40 ml MMC from 2012 to 2022. Optimal treatment was defined as 1-year maintenance for BCG and 11 monthly maintenance instillations for MMC. Kaplan-Meier analysis estimated recurrence-free survival (RFS) before and after inverse probability of treatment-weighting (IPTW) and progression-free survival (PFS). Multivariable Cox regression was used to evaluate difference in recurrence after adjustment for clinically relevant variables before and after IPTW. RESULTS: Optimal BCG and MMC courses were administered to 21% of IR-IBCG and 23% of IR-EAU patients. At 4-years, patients treated with optimal MMC and BCG treatment had similar RFS and PFS in both EAU and IBCG groups. Patients receiving nonoptimal BCG compared to optimal MMC exhibited lower 4-year RFS after IPTW (82% vs. 68% in EAU and 82% vs. 65% in IBCG). At 4-year optimal MMC had greater PFS non optimal BCG. Optimal MMC treatment predicted recurrence in EAU (adjusted and weighted HR 0.33, 95% CI, 0.11-0.98) and IBCG (adjusted and weighted HR 0.29, 95% CI, 0.08-0.97) groups compared to nonoptimal BCG. CONCLUSIONS: Optimal 40 mg/40 ml MMC treatment was as effective as optimal BCG in IR-IBCG and IR-EAU NMIBC patients, reducing both recurrence and progression compared to nonoptimal BCG. MMC could be a valid first line alternative to BCG for both IR-EAU and IR-IBCG intravescical treatment-naïve patients, during BCG shortages.

Comprehensive Analysis of a Six-Gene Signature Predicting Survival and Immune Infiltration of Liposarcoma Patients and Deciphering Its Therapeutic Significance.

BACKGROUND: As a common soft tissue sarcoma, liposarcoma (LPS) is a heterogeneous malignant tumor derived from adipose tissue. Due to the high risk of metastasis and recurrence, the prognosis of LPS remains unfavorable. To improve clinical treatment, a robust risk prediction model is essential to evaluate the prognosis of LPS patients. METHODS: By comprehensive analysis of data derived from GEO datasets, differentially expressed genes (DEGs) were obtained. Univariate and Lasso Cox regressions were subsequently employed to reveal distant recurrence-free survival (DRFS)-associated DEGs and develop a prognostic gene signature, which was assessed by Kaplan-Meier survival and ROC curve. GSEA and immune infiltration analyses were conducted to illuminate molecular mechanisms and immune correlations of this model in LPS progression. Furthermore, a correlation analysis was involved to decipher the therapeutic significance of this model for LPS. RESULTS: A six-gene signature was developed to predict DRFS of LPS patients and showed higher precision performance in more aggressive LPS subtypes. Then, a nomogram was further established for clinical application based on this risk model. Via GSEA, the high-risk group was significantly enriched in cell cycle-related pathways. In the LPS microenvironment, neutrophils, memory B cells and resting mast cells exhibited significant differences in cell abundance between high-risk and low-risk patients. Moreover, this model was significantly correlated with therapeutic targets. CONCLUSION: A prognostic six-gene signature was developed and significantly associated with cell cycle pathways and therapeutic target genes, which could provide new insights into risk assessment of LPS progression and therapeutic strategies for LPS patients to improve their prognosis.

IMPDH2 suppression impedes cell proliferation by instigating cell cycle arrest and stimulates apoptosis in pediatric hepatoblastoma.

BACKGROUND: Hepatoblastoma (HB) is the most common pediatric liver tumor, presenting significant therapeutic challenges due to its high rates of recurrence and metastasis. While Inosine Monophosphate Dehydrogenase 2(IMPDH2) has been associated with cancer progression, its specific role and clinical implications in HB have not been fully elucidated. METHODS: This study utilized Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Tissue Microarray (TMA) for validation. Following this, IMPDH2 was suppressed, and a series of in vitro assays were conducted. Flow cytometry was employed to assess apoptosis and cell cycle arrest. Additionally, the study explored the synergistic therapeutic effects of mycophenolate mofetil (MMF) and doxorubicin (DOX) on HB cell lines. RESULTS: The study identified a marked overexpression of IMPDH2 in HB tissues, which was strongly correlated with reduced Overall Survival (OS) and Event-Free Survival (EFS). IMPDH2 upregulation was also found to be associated with key clinical-pathological features, including pre-chemotherapy alpha-fetoprotein (AFP) levels, presence of preoperative metastasis, and the pre-treatment extent of tumor (PRETEXT) staging system. Knockdown of IMPDH2 significantly inhibited HB cell proliferation and tumorigenicity, inducing cell cycle arrest at the G0/G1 phase. Notably, the combination of MMF, identified as a specific IMPDH2 inhibitor, with DOX, substantially enhanced the therapeutic response. CONCLUSION: The overexpression of IMPDH2 was closely linked to adverse outcomes in HB patients and appeared to accelerate cell cycle progression. These findings suggest that IMPDH2 may serve as a valuable prognostic indicator and a potential therapeutic target for HB. IMPACT: The present study unveiled a significant overexpression of inosine monophosphate dehydrogenase 2 (IMPDH2) in hepatoblastoma (HB) tissues, particularly in association with metastasis and recurrence of the disease. The pronounced upregulation of IMPDH2 was found to be intimately correlated with adverse outcomes in HB patients. This overexpression appears to accelerate the progression of the cell cycle, suggesting that IMPDH2 may serve as a promising candidate for both a prognostic marker and a therapeutic target in the context of HB.

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.

Nonlinear association between PD-L1 expression levels and the risk of postoperative recurrence in non-small cell lung cancer.

Accurate prediction of postoperative recurrence is important for optimizing the treatment strategies for non-small cell lung cancer (NSCLC). Previous studies identified the PD-L1 expression in NSCLC as a risk factor for postoperative recurrence. This study aimed to examine the contribution of PD-L1 expression to predicting postoperative recurrence using machine learning. The clinical data of 647 patients with NSCLC who underwent surgical resection were collected and stratified into training (80%), validation (10%), and testing (10%) datasets. Machine learning models were trained on the training data using clinical parameters including PD-L1 expression. The top-performing model was assessed on the test data using the SHAP analysis and partial dependence plots to quantify the contribution of the PD-L1 expression. Multivariate Cox proportional hazards model was used to validate the association between PD-L1 expression and postoperative recurrence. The random forest model demonstrated the highest predictive performance with the SHAP analysis, highlighting PD-L1 expression as an important feature, and the multivariate Cox analysis indicated a significant increase in the risk of postoperative recurrence with each increment in PD-L1 expression. These findings suggest that variations in PD-L1 expression may provide valuable information for clinical decision-making regarding lung cancer treatment strategies.

Long-term survivors after curative-intent resection for intrahepatic cholangiocarcinoma.

OBJECTIVES: The objective of the current study was to characterize prognostic factors related to long-term recurrence-free survival after curative-intent resection of intrahepatic cholangiocarcinoma (ICC). METHODS: Data on patients who underwent curative-intent resection for ICC between 2000 and 2020 were collected from an international multi-institutional database. Prognostic factors were investigated among patients who recurred within 5 years versus long-term survivors who survived more than 5 years with no recurrence. RESULTS: Among 635 patients who underwent curative-intent resection for ICC, 104 (16.4%) patients were long-term survivors with no recurrence beyond 5 years after surgery. Patients who survived for more than 5 years with no recurrence were more likely to have less aggressive tumor features, as well as have undergone an R0 resection versus patients who recurred within 5 years after resection. On multivariable analysis, tumor size (>5 cm) (HR: 1.535, 95% CI: 1.254-1.879), satellite lesions (HR: 1.253, 95% CI: 1.003-1.564), and lymph node metastasis (HR: 1.733, 95% CI: 1.349-2.227) were independently associated with recurrence within 5 years. Patients who recurred beyond 5 years (n = 23), 2-5 years (n = 60), and within 2 years (n = 471) had an incrementally worse post-recurrence survival (PRS, 28.0 vs. 20.0 vs. 12.0 months, p = 0.032). Among patients with N0 status, tumor size (>5 cm) (HR: 1.612, 95% CI: 1.087-2.390) and perineural invasion (PNI) (HR: 1.562,95% CI: 1.081-2.255) were risk factors associated with recurrence. Among patients with N1 disease, only a minority (5/128, 3.9%) of patients survived with no recurrence to 5 years. CONCLUSION: Roughly 1 in 6 patients survived for more than 5 years with no recurrence following curative-intent resection of ICC. Among N0 patients, tumor recurrence was associated with tumor size and PNI. Only a small subset of N1 patients experienced long-term survival.

Development and validation of a nomogram to predict recurrence for clinical T1/2 clear cell renal cell carcinoma patients after nephrectomy.

OBJECTIVE: To develop and validate a nomogram for predicting recurrence-free survival (RFS) for clinical T1/2 (cT1/2) clear cell renal cell carcinoma (ccRCC) patients after nephrectomy. METHODS: Clinicopathological and survival data from 1289 cT1/2 ccRCC patients treated at the Second Hospital of Tianjin Medical University between 2017 and 2020 were included. Cox regression analysis was used to identify independent risk factors in 902 and 387 ccRCC patients in the training and validation cohorts, respectively, and construct the nomogram. The performance of the nomogram was assessed through calibration plots, time-dependent receiver operating characteristic (ROC) curves, C-index (concordance-index), and decision curve analysis (DCA). Kaplan-Meier curves were used to evaluate the probability of RFS in patients with different recurrence risks. RESULTS: Age, tumor size, surgical approach, Fuhrman grade, and pT3a upstage were identified as independent predictors of RFS. The area under the curve (AUC) for the 3-year and 5-year RFS ROC curves were 0.791 and 0.835 in the training cohort, and 0.860 and 0.880 in the validation cohort. The DCA and calibration plots demonstrated the optimal application and excellent accuracy of the nomogram for predicting 3-year and 5-year RFS. Kaplan-Meier curves revealed significant differences in RFS among the three risk groups in both the training and validation cohorts. Clinically, the developed nomogram provides a more precise tool for risk stratification, enabling tailored postoperative management and surveillance strategies, ultimately aiming to improve patient outcomes. CONCLUSIONS: We developed a nomogram for predicting RFS in cT1/2 ccRCC patients after nephrectomy with high accuracy. The clinical implementation of this nomogram can significantly enhance clinical decision-making, leading to improved patient outcomes and optimized resource utilization in the management of ccRCC.

Adjuvant imatinib in high-risk resected gastrointestinal stromal tumors: Merely delaying the inevitable?

INTRODUCTION: Patients with high-risk resected gastrointestinal stromal tumors (GIST) receiving adjuvant imatinib have improved recurrence-free survival (RFS), however whether a complete cytocidal effect exists is unknown. We investigated this using a normalized recurrence timeline measured from end of oncologic treatment (EOOT), defined as the later of resection or end of adjuvant therapy. METHODS: We reviewed patients with resected high-risk GIST at our cancer center from 2003 to 2018. RFS (measured from resection and EOOT), overall survival (OS), and time to imatinib resistance (TTIR) were analyzed using Kaplan-Meier analysis and multivariable Cox proportional hazards modeling. The performance of the Memorial Sloan Kettering (MSK) GIST nomogram was assessed. RESULTS: We identified 86 patients with high-risk GIST with a median 106 months of postsurgical follow-up. One-third (n = 29; 34%) did not receive adjuvant imatinib, while 57 (66%) did for a median of 3 years. The MSK nomogram-predicted 5-year RFS for patients receiving adjuvant imatinib was similar to those who did not (29% vs. 31%, p = 0.64). When RFS was measured from EOOT, the MSK-predicted RFS was independently associated with EOOT RFS (hazard ratio 0.22, p = 0.02), while adjuvant imatinib receipt and duration were not. Neither receipt nor duration of adjuvant imatinib were associated with TTIR or OS (all p > 0.05). CONCLUSIONS: Treatment with adjuvant imatinib delays, but does not clearly impact ultimate recurrence, TTIR, or OS, suggesting many patients with high-risk GIST may receive adjuvant imatinib unnecessarily. Additional studies are needed to establish the benefit of adjuvant therapy versus initiating therapy at first radiographic recurrence.

Machine learning-based model for predicting tumor recurrence after interventional therapy in HBV-related hepatocellular carcinoma patients with low preoperative platelet-albumin-bilirubin score.

Introduction: This study aimed to develop a prognostic nomogram for predicting the recurrence-free survival (RFS) of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with low preoperative platelet-albumin-bilirubin (PALBI) scores after transarterial chemoembolization (TACE) combined with local ablation treatment. Methods: We gathered clinical data from 632 HBV-related HCC patients who received the combination treatment at Beijing You'an Hospital, affiliated with Capital Medical University, from January 2014 to January 2020. The patients were divided into two groups based on their PALBI scores: low PALBI group (n=247) and high PALBI group (n=385). The low PALBI group was then divided into two cohorts: training cohort (n=172) and validation cohort (n=75). We utilized eXtreme Gradient Boosting (XGBoost), random survival forest (RSF), and multivariate Cox analysis to pinpoint the risk factors for RFS. Then, we developed a nomogram based on the screened factors and assessed its risk stratification capabilities and predictive performance. Results: The study finally identified age, aspartate aminotransferase (AST), and prothrombin time activity (PTA) as key predictors. The three variables were included to develop the nomogram for predicting the 1-, 3-, and 5-year RFS of HCC patients. We confirmed the nomogram's ability to effectively discern high and low risk patients, as evidenced by Kaplan-Meier curves. We further corroborated the excellent discrimination, consistency, and clinical utility of the nomogram through assessments using the C-index, area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Conclusion: Our study successfully constructed a robust nomogram, effectively predicting 1-, 3-, and 5-year RFS for HBV-related HCC patients with low preoperative PALBI scores after TACE combined with local ablation therapy.

Preoperative neutrophil-to-lymphocyte ratio predicts recurrence of esophageal squamous cell carcinoma after neoadjuvant triplet chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy followed by esophagectomy is the standard treatment for resectable advanced esophageal squamous cell carcinoma (ESCC) in Japan. Triplet chemotherapy is the standard neoadjuvant regimen. Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR) are well-known prognostic factors for esophageal cancer. However, their usefulness in patients with resectable advanced disease undergoing esophagectomy after neoadjuvant triplet chemotherapy is unknown. METHOD: We examined 144 ESCC patients who underwent neoadjuvant triplet chemotherapy followed by esophagectomy between January 2015 and December 2020 to investigate the relationship between inflammatory markers and recurrence-free survival (RFS). Optimal marker cutoff values for RFS were determined using receiver operating characteristic curve analysis. Patients were divided into high and low NLR groups (NLR cutoff, 3.0). RESULTS: NLR was high in 61 patients and low in 83. Univariate analyses demonstrated that low NLR was significantly associated with worse RFS (p = 0.049). Multivariate analyses demonstrated that high NLR was an independent predictor of RFS (odds ratio, 1.911; 95% confidence interval, 1.098-3.327; p = 0.022). RFS significantly differed between the low and high NLR groups. RFS did not significantly differ between the patients when stratified according to the other inflammatory markers. CONCLUSION: Preoperative NLR is an easily obtained and useful predictor of RFS in patients with resectable advanced ESCC treated with neoadjuvant triplet chemotherapy followed by esophagectomy.

Role of frailty in predicting prognosis of older patients with lung cancer: An updated systematic review and meta-analysis.

INTRODUCTION: Frailty is a syndrome affecting primarily older adults that can impact disease course, treatment, and outcomes in patients with lung cancer (LC). We systematically reviewed current data on the correlation between frailty and overall survival (OS), recurrence-free survival (RFS), and the risk of complications in older patients with LC. MATERIALS AND METHODS: PubMed, EMBASE, and Scopus databases were searched for observational cohort, cross-sectional, and case-control studies involving participants aged 18 years or older diagnosed with LC. Eligible studies were required to perform frailty assessments and have non-frail participants as a comparator group. Random-effects models were used for analysis, and the reported effect sizes were represented as hazards ratio (HR) or odds ratios (OR) with associated 95% confidence intervals (CI). RESULTS: Seventeen studies were included, most with a retrospective cohort design (n = 16) and patients with non-small cell lung carcinoma (NSCLC). Older patients with LC and frailty had lower OS (HR 1.70, 95% CI: 1.39, 2.07) and RFS (HR 2.50, 95% CI: 1.02, 6.12), compared to non-frail subjects. Frail subjects also had increased risk of complications (OR 1.89, 95% CI: 1.42, 2.53). DISCUSSION: The observed association between frailty and OS, RFS, and an increased susceptibility to complications emphasizes the potential significance of frailty status as a substantial prognostic indicator. Our results underscore the vital role of including frailty assessment as an integral element within the management plan for patients dealing with lung cancer.