Outcomes of Robot-Assisted Versus Laparoscopic Surgery for Colorectal Cancer in Adults ≥ 75 Years Old: A Propensity Score Matched Analysis of the US Nationwide Inpatient Sample.

BACKGROUND: Robot-assisted surgery has been increasingly adopted in colorectal cancer resection. OBJECTIVE: The study aimed to compare the inpatient outcomes of robot-assisted versus conventional laparoscopic colorectal cancer resection in patients ≥ 75 years. DESIGN: A retrospective, population-based study. SETTINGS: This study analyzed data from the United States Nationwide Inpatient Sample from 2005 to 2018. PATIENTS: Colorectal cancer patients ≥ 75 years old and underwent robot-assisted or conventional laparoscopic resection. MAIN OUTCOME MEASURES: Postoperative complication, prolonged length of stay, and total hospital costs were assessed. RESULTS: Data from 14,108 patients were analyzed. After adjustment, any postoperative complications (aOR = 0.87, 95% CI: 0.77-0.99, p = 0.030) and prolonged length of stay (aOR = 0.78, 95% CI: 0.67-0.91, p = 0.001) were significantly less in the robotic than the laparoscopic group. In addition, robotic surgery was associated with significantly higher total hospital costs ($26.06 USD greater cost; 95% CI: 21.35-30.77 USD, p < 0.001). LIMITATIONS: The analysis was limited by its retrospective and observational nature, potential coding errors, and the lack of intraoperative factors such as operative time, laboratory measures, and information on surgeons' experience. CONCLUSIONS: In United States, patients with colorectal cancer ≥ 75 years who were undergoing tumor resections, compared to conventional laparoscopic surgery, robotic surgery is associated with better inpatient outcomes in terms of complication rate and risk of prolonged length of stay, especially among patients with colon cancer. However, robotic surgery is associated with higher total hospital costs.

Long-term use and risk of major adverse cardiac events: Comparing enzalutamide and abiraterone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer.

This is a retrospective cohort study by analyzing a multi-institutional electronic medical records database in Taiwan to compare long-term effectiveness and risk of major adverse cardiac events (MACE) in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients treated with enzalutamide (ENZ) or abiraterone (AA). Patients aged 20 years and older and newly receiving androgen receptor targeted therapies ENZ or AA from September 2016 to December 2019 were included. We followed patients from initiation of therapies to the occurrence of outcomes (prostate-specific antigen (PSA) response rate, PSA progression free survival (PFS), overall survival (OS), and MACE), death, the last clinical visit, or December 31, 2020. We performed multivariable Cox proportional hazard models to compare ENZ and AA groups for the measured outcomes. A total of 363 patients treated with either ENZ (n = 157) or AA (n = 206) were identified. The analysis found a significantly higher proportion of patients with a PSA response rate higher than 50% among those receiving ENZ than among those receiving AA (ENZ vs AA: 75.80% vs 63.59%, P = .01). However, there was no significant difference in PSA PFS (adjusted hazard ratio: 0.86; 95% CI 0.63-1.17) and OS (0.68: 0.41-1.14) between the use of ENZ and AA in chemotherapy-naïve mCRPC patients. Regarding the cardiovascular (CV) safety outcome, there was a significantly lower risk of MACE in patients receiving ENZ, compared to patients receiving AA (0.20: 0.07-0.55). The findings suggest that enzalutamide may be more efficacious for PSA response and suitable for chemotherapy-naïve mCRPC patients with high CV risk profile.

Novel prognostic implications of complement activation in the tumour microenvironment for de novo metastatic BRAF V600E mutant colorectal cancer.

BACKGROUND: Prognosis of metastatic BRAF V600E mutant colorectal cancer (CRC) is poor, and the prognostic implications of immune contextures in the tumour microenvironment (TME) for CRC remain elusive. METHODS: We collected the primary tumour specimens and clinicopathological characteristics of patients with de novo metastatic microsatellite-stable BRAF V600E mutant CRC from two medical centres. Gene expression analysis was performed using the nCounterⓇ PanCancer Immune Profiling Panel. The Cox proportional hazards regression model was used for analysing survival outcomes in association with immune gene expression and immune cells. Our complement score was defined on the basis of the average gene expression in the selected co-expression module. RESULTS: High expression of classical and regulatory complement genes was significantly associated with poor prognosis (N = 54). A high complement score (defined as a score above the median value) indicated significantly shorter survival. The overall survival (OS) impact of the high score remained significant in multivariate analyses. Additionally, our complement score was strongly correlated with C4d expression in immunohistochemical staining and tumour-associated macrophage (TAM) M2 signatures. CONCLUSIONS: Complement activation in the TME was significantly associated with poor OS and was correlated with TAM M2 in patients with de novo metastatic BRAF V600E mutant CRC.

The prognostic significance of histologic variant on survival outcomes in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitor therapy.

BACKGROUND: While the treatment guidelines have been established for pure urothelial carcinoma (pUC), patients with variant type urothelial carcinoma (vUC) face limited effective treatment options. The effectiveness of immune checkpoint inhibitors (ICI) in patients with vUC remains uncertain and necessitates additional research. METHOD: We conducted a retrospective, multicenter study to explore the effectiveness of ICI in patients with pUC or vUC in Taiwan. We evaluated the overall response rate (ORR) through univariate logistic regression analysis and examined the overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analysis. Additionally, we employed univariate and multivariate Cox proportional hazards models to analyze the data. RESULT: A total of 142 patients (116 pUC, 26 vUC) were included in our final analysis. The ORR was marginally higher in patients with pUC compared to those with vUC (34.5% vs. 23.1%, p = 0.26). Among all patients, 12.9% with pUC achieved a complete response (CR) after ICI treatment, while no vUC cases achieved CR (p = 0.05). There were no significant differences in PFS (median 3.6 months vs. 4.1 months, p = 0.34) or OS (median 16.3 months vs. 11.0 months, p = 0.24) when comparing patients with pUC or vUC. In the subgroup analysis, patients with pUC who underwent first-line ICI treatment exhibited significantly improved OS compared to those with vUC (24.6 months vs. 9.1 months, p = 0.004). CONCLUSION: The use of ICI as monotherapy is a feasible and effective treatment approach for patients with metastatic vUC.

Chitinase 3-like-1 Expression in the Microenvironment Is Associated with Neutrophil Infiltration in Bladder Cancer.

Bladder cancer is a common cancer with well-established therapeutic strategies. However, recurrence occurs in 50% of patients with non-muscle-invasive bladder cancer, and 20% of patients progress to muscle-invasive bladder cancer. The 5-year survival rate for muscle-invasive bladder cancer patients is disappointingly low, ranging from 36% to 48%. A molecular marker of interest is chitinase 3-like-1 (CHI3L1), which is elevated in various cancers, including bladder cancer. In addition to its role in cancer cells, CHI3L1 also has regulatory abilities in immune cells. Neutrophil infiltration has been shown to positively correlate with overall survival, progression-free survival, and relapse-free survival in bladder cancer patients. However, the relationship between CHI3L1 and neutrophils remain poorly understood. Therefore, this study investigated the relationship between CHI3L1 level and protumor neutrophil infiltration in bladder cancer. We analyzed the GSE128959 dataset and the data of a bladder cancer cohort undergoing chemotherapy. We observed higher expression of CHI3L1 in bladder cancer patients with invasive or chemotherapy-resistance. Our results revealed a positive correlation between CHI3L1 expression and protumor neutrophil infiltration. Elevated CHI3L1 expression was associated with genes which were related to the recruitment and infiltration of neutrophils. Consequently, CHI3L1 may serve as a novel evaluation factor for the degree of neutrophil infiltration in advanced bladder cancer in those scheduled for chemotherapy.

VCAN Hypomethylation and Expression as Predictive Biomarkers of Drug Sensitivity in Upper Urinary Tract Urothelial Carcinoma.

Versican (VCAN), also known as extracellular matrix proteoglycan 2, has been suggested as a potential biomarker in cancers. Previous research has found that VCAN is highly expressed in bladder cancer. However, its role in predicting outcomes for patients with upper urinary tract urothelial cancer (UTUC) is not well understood. In this study, we collected tissues from 10 patients with UTUC, including 6 with and 4 without lymphovascular invasion (LVI), a pathological feature that plays a significant role in determining metastasis. Results from RNA sequencing revealed that the most differentially expressed genes were involved in extracellular matrix organization. Using the TCGA database for clinical correlation, VCAN was identified as a target for study. A chromosome methylation assay showed that VCAN was hypomethylated in tumors with LVI. In our patient samples, VCAN expression was also found to be high in UTUC tumors with LVI. In vitro analysis showed that knocking down VCAN inhibited cell migration but not proliferation. A heatmap analysis also confirmed a significant correlation between VCAN and migration genes. Additionally, silencing VCAN increased the effectiveness of cisplatin, gemcitabine and epirubicin, thus providing potential opportunities for clinical application.

Adult NTRK-rearranged spindle cell neoplasms of the viscera: with an emphasis on rare locations and heterologous elements.

NTRK-rearranged mesenchymal neoplasms mostly affect the soft tissues of pediatric patients. Given the responsiveness to selective NTRK inhibitors, it remains critical to identify those ultra-rare cases occurring in the viscera of adults. In five females and two males aged 18-53 years, we characterized visceral mesenchymal tumors harboring TPM3-NTRK1 [uterine cervix (N = 2), pleura, prostate], LMNA-NTRK1 (lung), SQSTM1-NTRK3 (heart), and NTRK3 rearrangement with unknown fusion partner (colon/mesocolon) with RNA sequencing, FISH, RT-PCR, and immunohistochemistry. The tumors exhibited spindled to ovoid/epithelioid or pleomorphic cells, often arranged in fascicles, and were low-to-intermediate-grade and high-grade in three and four cases, respectively. Keloid-like stromal collagen and perivascular hyalinization was noted in five. Adenosarcoma-like appearances were observed in two, manifesting frond-like protrusions in one cervical tumor and phyllodes-like architecture in the prostatic tumor. Abrupt high-grade transformation into pleomorphic liposarcoma was found in another cervical tumor, while the pleural tumor contained intermixed rhabdomyoblasts. Pan-TRK immunostaining was positive in all cases. All cases expressed CD34, while five were S100-positive. CDKN2A homozygous deletion with concomitant p16 loss occurred in 4/7. Whole-exome sequencing identified TP53 mutation (c.672+2T>C, involving a splice site, with concomitant protein loss) in a cervical sarcoma, limited to its heterologous liposarcomatous component. At least moderate pan-TRK immunoreactivity was present in varying proportions of potential pathologic mimics, with BCOR-positive sarcoma (56%, 5/9), undifferentiated uterine sarcoma (50%, 3/6), and spindle cell/sclerosing rhabdomyosarcoma (33%, 2/6) being among the most frequent. This underscored the unsatisfactory specificity of pan-TRK immunohistochemistry and warranted molecular confirmation in the diagnosis of adult NTRK-rearranged visceral mesenchymal neoplasms. The current report highlights the ever-expanding clinicopathologic and genetic spectrum of this entity by describing the unprecedented cardiac and pleural locations and heterologous differentiation, as well as the second NTRK-rearranged "prostatic stromal sarcoma," while substantiating CDKN2A deletion as a frequent occurrence.

Confirming whether KLHL23 deficiency potentiates migration in urothelial carcinoma.

Epithelial-mesenchymal transition (EMT) is associated with malignant tumors. In a previous study, we found that KLHL23 is a tumor suppressor gene that inhibits EMT and cancer dissemination. However, the correlation between its expression and cancer progression in urothelial carcinoma (UC) remains unknown. This study showed that the deficiency of KLHL23 in the invasive leading cancer cells is important for improving cell migration in UC. Currently, little is known about the underlying mechanisms of KLHL23-mediated cytoskeleton remodeling in the metastatic leading cells of tumors. Our findings showed that silencing of KLHL23 promotes cell migration in UC by regulating the translocation of focal adhesion proteins. Lack of KLHL23 causes abnormal formation of lamellipodia and increases the EMT phenotype and migration. Wound healing assay revealed that KLHL23 potentiates the actin bundles and intracellular focal adhesion protein formation in the invasive leading cells. Knockdown of KLHL23 abolishes the formation of actin stress fibers and translocalizes vinculin to the perimembrane, which enhances the mobility of cancer cells. To elucidate the mechanism, we found that during migration, KLHL23 appears in the leading cells in large numbers and binds to the actin stress fibers. A large amount of vinculin accumulated at both ends of the KLHL23/actin fibers, indicating an increase in cell anchorage. Thus, KLHL23 might play a critical role in enhancing actin fibers and promoting focal adhesion complex formation in the invasive leading cells. Analysis of the overall survival revealed that low KLHL23 is associated with poor survival in patients with bladder UC, indicating its clinical significance. We hypothesize that KLHL23 is involved in the formation of actin stress fibers and focal adhesion complexes in the invasive leading cells and may be associated with EMT progression and prognosis in UC patients.

Hypomethylated RRBP1 Potentiates Tumor Malignancy and Chemoresistance in Upper Tract Urothelial Carcinoma.

Ribosome-binding protein 1 (RRBP1) is a potential oncogene in several cancer types. However, the correlation between RRBP1 expression and the prognosis of patients with upper tract urothelial carcinoma (UTUC) remains unclear. In this study, we identified that RRBP1 is associated with carcinogenesis and metastasis in UTUC using a methylation profiling microarray. High correlations between RRBP1 and cancer stages, nodal metastasis status, molecular subtypes, and prognosis in bladder urothelial cancer (BLCA) were found. Aberrant DNA methylation in the gene body region of RRBP1 was determined in UTUC tissues by methylation-specific PCR. RRBP1 expression was significantly increased in UTUC tissues and cell lines, as determined by real-time PCR and immunohistochemistry. RRBP1 depletion significantly reduced BFTC909 cell growth induced by specific shRNA. On the other hand, molecular subtype analysis showed that the expression of RRBP1 was associated with genes related to cell proliferation, epithelial-mesenchymal transition, and basal markers. A patient-derived organoid model was established to analyze patients' responses to different drugs. The expression of RRBP1 was related to chemoresistance. Taken together, these results provide the first evidence that RRBP1 gene body hypomethylation predicts RRBP1 high expression in UTUC. The data highlight the importance of RRBP1 in UTUC malignancy and chemotherapeutic tolerance.

A Narrative Review of Complementary Nutritional Supplements for Chemotherapy-induced Peripheral Neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common troublesome side effect and affects long-term activities of daily living. This neuropathic disorder is still difficult to treat with current clinical treatments. The aim of this study was to investigate and offer an updated perspective of complementary therapies for CIPN. METHODS: This review included current databases, including PubMed, Embase, the Cochrane Database, Google Scholar, and Ovid Medline, published up to May 2019 in the English language, to summarize the role of nutrient supplements in CIPN, based on evidence from both animal and clinical studies. RESULTS: A total of 58 studies were included in this review. There were 19 preclinical studies that reported mechanisms of effects and 31 clinical studies corroborated preclinical findings, including 22 randomized controlled trials and 3085 patients with CIPN. Interventions included vitamin E, vitamin B complex, glutamine, acetyl-L-carnitine, alpha lipoic acid, glutathione, omega-3 fatty acids, and calcium/magnesium (Ca2+/Mg2+). The administration of various nutrients remains inconsistent, and limited evidence of effective ones for treating CIPN is available. However, glutamine and omega-3 fatty acids present potential as treatment options for CIPN. The evidence on vitamin E and vitamin B complex is inconclusive, and some forms of vitamin B, such as B6 or B12, await confirmation of their potential to offer protection from CIPN. Less robust evidence was found for nutrients such as acetyl-L-carnitine, α-Lipoic acid, glutathione, and Ca2+/Mg2+ for CIPN. CONCLUSION: Nutritional therapists seem to recommend nutrient supplements as potential anti-inflammatory and neuroprotective agents for both the prevention and management of CIPN. An understanding of this evolving literature is useful in exploring these therapies with patients who are considering using them. However, their effects against CIPN are still controversial due to the undetermined neuropathic mechanisms of different antineoplastic agents and complex drug interactions. Further research on these agents is warranted.

Proteomics Analysis of Tangeretin-Induced Apoptosis through Mitochondrial Dysfunction in Bladder Cancer Cells.

Tangeretin is one of the most abundant compounds in citrus peel, and studies have shown that it possesses anti-oxidant and anti-cancer properties. However, no study has been conducted on bladder cancer cells. Bladder cancer has the second highest mortality rate among urological cancers and is the fifth most common malignancy in the world. Currently, combination chemotherapy is the most common approach by which to treat patients with bladder cancer, and thus identifying more effective chemotherapeutic agents that can be safely administered to patients is a very important research issue. Therefore, this study investigated whether tangeretin can induce apoptosis and identified the signaling pathways of tangeretin-induced apoptosis in human bladder cancer cells using two-dimensional gel electrophoresis (2DGE). The results of the study demonstrated that 60 µM tangeretin reduced the cell survival of a BFTC-905 bladder carcinoma cell line by 42%, and induced early and late apoptosis in the cells. In this study 2DGE proteomics technology identified 41 proteins that were differentially-expressed in tangeretin-treated cells, and subsequently LC⁻MS/MS analysis was performed to identify the proteins. Based on the functions of the differentially-expressed proteins, the results suggested that tangeretin caused mitochondrial dysfunction and further induced apoptosis in bladder cancer cells. Moreover, western blotting analysis demonstrated that tangeretin treatment disturbed calcium homeostasis in the mitochondria, triggered cytochrome C release, and activated caspase-3 and caspase-9, which led to apoptosis. In conclusion, our results showed that tangeretin-induced apoptosis in human bladder cancer cells is mediated by mitochondrial inactivation, suggesting that tangeretin has the potential to be developed as a new drug for the treatment of bladder cancer.

Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma.

Advanced upper urinary tract urothelial carcinoma (UTUC) is often associated with poor oncologic outcomes. The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) protein, belongs to the SPARC-related family of matricellular proteins. Much literature has been published describing the role of SPARCL1 in the prognosis many cancers. In this study, methylated promoter regions in high-grade and high-stage upper urinary urothelial tumours compared with normal urothelium were analyzed and revealed that SPARCL1 was the most significantly hypermethylated gene in UTUC tissues. Then we prospectively collected UTUC samples and adjacent normal urothelium for pyrosequencing validation, identifying significant CpG site methylation in UTUC tissues. In addition, SPARCL1 RNA levels were significantly lower in UTUC samples. Multivariate Cox regression analysis from 78 patients with solitary renal pelvic or ureteral pT3N0M0 urothelial carcinomas revealed that only negative SPARCL1 expression and nonpapillary tumour architecture were independently associated with systemic recurrence (p = 0.011 and 0.008, respectively). In vitro studies revealed that the behaviour of BFTC-909 cells was less aggressive and more sensitive to radiation or chemotherapy after SPARCL1 overexpression. Thus, SPARCL1 could be considered as a prognostic marker and help decision-making in clinical practice.

Aristolochic Acid Affects Upper Tract Urothelial Cancer Behavior through the MAPK Pathway.

The prevalence of upper tract urothelial carcinoma (UTUC) in Taiwan is relatively higher than thatin Western countries. Aristolochic acid (AA), which is widely used in traditional Chinese herbology, is now recognized to be one of the carcinogens for UTUC. Numerous UTUC patients have chronic kidney diseases or end-stage renal diseases; however, little literature hasreported on theoncogenic pathway of AA-related UTUC. The aim of our study was to identify the potential target treatment for AA-related UTUC. Here, we established an AA pre-exposure followed bya 3-methylcholanthrene (MCA) stimulus tumorigenic cell model. We not only demonstrated that AA pre-exposure MCA stimulus tumorigenic cells have more behaviors of cell migration and invasion by enhancing the metalloproteinases (MMP) activity, which is compatible with clinical findings of AA-related UTUC, but we also validated that AA pre-exposure MCA stimulus tumorigeniccells could be activated through the mitogen-activated protein kinases (MAPK) pathway. We further dissected the route of the MAPK pathway and found that the p38 and extracellular signal regulated kinases (ERK) sub-pathways might play essential roles in AA pre-exposure urothelial cancer cell lines. This consequence was also corroborated with a tissue study in AA-exposed patients.

A preliminary randomised controlled study of short-term Antrodia cinnamomea treatment combined with chemotherapy for patients with advanced cancer.

BACKGROUND: Antrodia cinnamomea (AC) is a popular medicinal mushroom in Taiwan that has been widely used for treatment of various cancers. Few clinical studies have reported its application and efficiency in therapeutic chemotherapy strategies. We performed a double-blind, randomized clinical study to investigate whether AC given for 30 days had acceptable safety and efficacy in advanced cancer patients receiving chemotherapy. METHODS: Patients with advanced and/or metastatic adenocarcinoma, performance status (PS) 0-2, and adequate organ function who had previously been treated with standard chemotherapy were randomly assigned to receive routine chemotherapy regimens with AC (20 ml twice daily) orally for 30 days or placebo. The primary endpoint was 6-month overall survival (OS); the secondary endpoints were disease control rate (DCR), quality of life (QoL), adverse event (AE), and biochemical features within 30 days of treatment. RESULTS: From August 2010 to July 2012, 37 subjects with gastric, lung, liver, breast, and colorectal cancer (17 in the AC group, 20 in the placebo group) were enrolled in the study. Disease progression was the primary cause of death in 4 (33.3 %) AC and 8 (66.7 %) placebo recipients. Mean OSs were 5.4 months for the AC group and 5.0 months for the placebo group (p = 0.340), and the DCRs were 41.2 and 55 %, respectively (p = 0.33). Most hematologic, liver, or kidney functions did not differ significantly between the two groups, but platelet counts were lower in the AC group than in the placebo group (p = 0.02). QoL assessments were similar in the two groups, except that the AC group showed significant improvements in quality of sleep (p = 0.04). CONCLUSIONS: Although we found a lower mortality rate and longer mean OS in the AC group than in the control group, A. cinnamomea combined with chemotherapy was not shown to improve the outcome of advanced cancer patients, possibly due to the small sample size. In fact, the combination may present a potential risk of lowered platelet counts. Adequately powered clinical trials will be necessary to address this question. TRIAL REGISTRATION: ClinicalTrials.gov NCT01287286 .

Prognostic model to predict survival in patients with metastatic upper tract urothelial carcinoma treated with cisplatin-based chemotherapy.

OBJECTIVES: To create a novel prognostic model to predict survival in metastatic upper tract urothelial carcinoma patients treated with cisplatin-based chemotherapy. METHODS: After institutional review board approval, patients who had metastatic upper tract urothelial carcinoma and were treated with cisplatin based chemotherapy from 2000 to 2012 at Kaohsiung Chang Gung Memorial Hospital were retrospectively reviewed. Significantly predictive factors were identified by multivariate Cox regress analyses. Kaplan-Meier curves were plotted to estimate overall survival. Several prognostic models were validated by using our cohort, and Harrell's c-index was calculated to evaluate their predicting performances. RESULTS: The present study consisted of 136 patients with a median age of 62 years and a median follow-up visit of 13.6 months. Multivariate analyses showed that renal function, performance status, liver metastasis and number of metastatic sites was independently related to survival. Based on these four variables, we constructed a prognostic model "renal function, performance status, liver metastasis, number of metastatic sites" with significantly different survival (P < 0.001). C-index results were renal function, performance status, liver metastasis, number of metastatic sites model 0.80 (0.69-0.90), Bajorin model 0.72 (0.61-0.83), Taguchi model 0.77 (0.67-0.87) and Tanaka model 0.78 (0.69-0.88). Our renal function, performance status, liver metastasis, number of metastatic sites prognostic model achieved the highest c-index in this study. CONCLUSIONS: Our renal function, performance status, liver metastasis, number of metastatic sites prognostic model could be useful for providing prognostic information on survival in patients with metastatic upper tract urothelial carcinoma.

Intra-arterial chemotherapy with doxorubicin and cisplatin is effective for advanced hepatocellular cell carcinoma.

UNLABELLED: Advanced hepatocellular carcinoma (HCC) remains a fatal disease even in the era of targeted therapies. Intra-arterial chemotherapy (IACT) can provide therapeutic benefits for patients with locally advanced HCC who are not eligible for local therapies or are refractory to targeted therapies. The aim of this retrospective study was to analyze the effect of IACT with cisplatin and doxorubicin on advanced HCC. METHODS: Patients with advanced HCC who were not eligible for local therapies or were refractory to sorafenib received doxorubicin (50 mg/m(2)) and cisplatin (50 mg/m(2)) infusions into the liver via the transhepatic artery. Between January 2005 and December 2011, a total of 50 patients with advanced HCC received this treatment regimen. The overall response rate (ORR) was 22% in all treated patients. In patients who received at least 2 cycles of IACT, the ORR was 36.7%, and the disease control rate was 70%. Survival rate differed significantly between patients who received only one cycle of IACT (group I) and those who received several cycles (group II). The median progression-free survival was 1.3 months and 5.8 months in groups I and II, respectively (P < 0.0001). The median overall survival was 8.3 months for all patients and was 3.1 months and 12.0 months in groups I and II, respectively (P < 0.0001). The most common toxicity was alopecia. Four patients developed grade 3 or 4 leukopenia. Worsening of liver function, nausea, and vomiting were uncommon side effects. This study demonstrated clinical efficacy and tolerable side effects of repeated IACT with doxorubicin and cisplatin in advanced HCC. Our regimen can be an alternative choice for patients with adequate liver function who do not want to receive continuous infusion of IACT.

Post-mastectomy radiotherapy benefits subgroups of breast cancer patients with T1-2 tumor and 1-3 axillary lymph node(s) metastasis.

BACKGROUND: To determine the role of postmastectomy radiotherapy (PMRT) in breast cancer patients with T1-2 and N1 disease. PATIENTS AND METHODS: A total of 207 postmastectomy women were enrolled. The 5-year Kaplan-Meier estimates of locoregional recurrence rate (LRR), distant recurrence rate (DRR) and overall survival (OS) were analyzed by different tumor characteristics. Multivariate analyses were performed using Cox proportional hazards modeling. RESULTS: With median follow-up 59.5 months, the 5-year LRR, DRR and OS were 9.1%, 20.3% and 84.4%, respectively. On univariate analysis, age < 40 years old (p = 0.003) and Her-2/neu over-expression (p = 0.016) were associated with higher LRR, whereas presence of LVI significantly predicted higher DRR (p = 0.026). Negative estrogen status (p = 0.033), Her-2/neu overexpression (p = 0.001) and LVI (p = 0.01) were significantly correlated with worse OS. PMRT didn't prove to reduce 5-year LRR (p = 0.107), as well as 5-year OS (p = 0.918). In subgroup analysis, PMRT showed significant benefits of improvement LRR and OS in patients with positive LVI. CONCLUSIONS: For patients with T1-2 and N1 stage breast cancer, PMRT can decrease locoregional recurrence and increase overall survival only in patients with lymphovascular invasion.

Association between Statin Use and Clinical Outcomes in Patients with De Novo Metastatic Prostate Cancer: A Propensity Score-weighted Analysis.

PURPOSE: Numerous studies have produced conflicting findings regarding the efficacy of statins in prostate cancer treatment. Our objective was to examine the correlation between statin usage and clinical outcomes in Taiwanese men with de novo metastatic prostate cancer. MATERIALS AND METHODS: We identified patients diagnosed with de novo metastatic prostate cancer from the Chang Gung Research Database spanning the years 2007 to 2020. To minimize confounding bias, we employed the inverse probability of treatment weighting (IPTW) method. Clinical outcomes were assessed using IPTW-adjusted Kaplan-Meier curves. Multivariate Cox proportional hazard regression analysis was utilized to evaluate the association between mortality and clinical factors. RESULTS: The study cohort comprised 1,716 statin users and 276 non-users. Patients who used statins exhibited a longer median overall survival (85.4 months compared to 58.2 months; p=0.001) and cancer-specific survival (112.6 months compared to 75.7 months; p<0.001) compared to non-users. The median time to the development of castration-resistant status was similar between statin users and non-users (p=0.069). Multivariable Cox proportional hazards regression analysis, after IPTW adjustment, demonstrated that statin use was associated with improved overall survival. CONCLUSIONS: Our study indicates that the use of statins following a de novo metastatic prostate cancer diagnosis enhances survival outcomes. However, statins did not appear to delay the onset of castration-resistant status. Further large-scale and long-term studies are warranted to investigate the biological effects of statins in men with prostate cancer.

The impact of body mass index on survival endpoints among patients with metastatic urothelial carcinoma undergoing treatment with immune checkpoint inhibitors: A real-world multicenter analysis.

BACKGROUND: Studies on the correlation between high body mass index (BMI) and extended survival among patients receiving immune checkpoint inhibitors (ICIs) have been made, although findings have shown variability. Our research explored the phenomenon of the "obesity paradox" in patients with metastatic urothelial carcinoma (mUC) undergoing treatment with ICIs. MATERIALS AND METHODS: We conducted a retrospective analysis of patients diagnosed with mUC who received a minimum of one cycle of ICI treatment at two medical centers in Taiwan from September 2015 to January 2023. Features of patients' clinicopathologic factors, including age, sex, primary or metastatic location, treatment line, and BMI were examined. The primary outcome were overall survival (OS) and progression-free survival (PFS), which were assessed utilizing the Kaplan-Meier method. We employed the Cox-regression model to adjust for multiple covariates. RESULTS: A total of 215 patients were included, with 128 (59.5%) being male, and the median age was 70 years. In the obese group (BMI ≥25 kg/m2 ), patients demonstrated significantly better median OS compared to the non-obese group (BMI <25 kg/m2 ) (21.9 vs. 8.3 months; p = 0.021). However, there was no significant difference in median PFS between the high and low BMI groups (4.7 vs. 2.8 months; p = 0.16). Post-hoc subgroup revealed a survival benefit from ICI treatment in male patients within the BMI ≥25 kg/m2 group (HR 0.49, 95% CI 0.30-0.81, p = 0.005). CONCLUSION: Based on real-world data from the Asia-Pacific region, there appears to be a correlation between obesity and prolonged OS in patients receiving ICI treatment for mUC.

Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial.

BACKGROUND: Pembrolizumab plus lenvatinib has shown antitumor activity and acceptable safety in patients with platinum-refractory urothelial carcinoma (UC). OBJECTIVE: To evaluate pembrolizumab plus either lenvatinib or placebo as first-line therapy for advanced UC in the phase 3 LEAP-011 study. DESIGN, SETTING, AND PARTICIPANTS: Patients with advanced UC who were ineligible for cisplatin-based therapy or any platinum-based chemotherapy were enrolled. INTERVENTION: Patients were randomly assigned (1:1) to pembrolizumab 200 mg intravenously every 3 wk plus either lenvatinib 20 mg or placebo orally once daily. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Dual primary endpoints were progression-free survival (PFS) and overall survival (OS). An external data monitoring committee (DMC) regularly reviewed safety and efficacy data every 3 mo. RESULTS AND LIMITATIONS: Between June 25, 2019 and July 21, 2021, 487 patients were allocated to receive lenvatinib plus pembrolizumab (n = 245) or placebo plus pembrolizumab (n = 242). The median time from randomization to the data cutoff date (July 26, 2021) was 12.8 mo (interquartile range, 6.9-19.3). The median PFS was 4.5 mo in the combination arm and 4.0 mo in the pembrolizumab arm (hazard ratio [HR] 0.90 [95% confidence interval {CI} 0.72-1.14]). The median OS was 11.8 mo for the combination arm and 12.9 mo for the pembrolizumab arm (HR 1.14 [95% CI 0.87-1.48]). Grade 3-5 adverse events attributed to trial treatment occurred in 123 of 241 patients (51%) treated with lenvatinib plus pembrolizumab and in 66 of 242 patients (27%) treated with placebo plus pembrolizumab. This trial was terminated earlier than initially planned based on recommendation from the DMC. CONCLUSIONS: The benefit-to-risk ratio for first-line lenvatinib plus pembrolizumab was not considered favorable versus pembrolizumab plus placebo as first-line therapy in patients with advanced UC. PATIENT SUMMARY: Lenvatinib plus pembrolizumab was not more effective than pembrolizumab plus placebo in patients with advanced urothelial carcinoma.