Survival Benefit In Patients Research Articles

Efficacy of PD-1 inhibitor plus chemotherapy versus chemotherapy in advanced esophageal carcinoma: A meta-analysis of phase III clinical trials.

397 Background: Programmed death cell death protein-1 (PD-1) inhibitors combined with chemotherapy have demonstrated survival benefits in patients with advanced esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). Our pooled analysis aims to analyze the efficacy of PD-1 inhibitor plus chemotherapy in advanced esophageal carcinoma (EC) in phase III randomized clinical trials (RCTs). Methods: We collected data from eligible phase III RCTs searched through PubMed, EMBASE, ClinicalTrials.gov, and meeting abstracts till July 5, 2024. Initial screening revealed 792 articles. We excluded duplicates, review articles and irrelevant studies, and we included eight RCTs that reported objective response rate (ORR), treatment-related adverse events (TRAEs), overall survival (OS) and progression-free survival (PFS). Odds ratio (OR) for ORR and TRAEs, and hazard ratio (HR) for OS and PFS were computed along with a 95% confidence interval (CI) and p-value for pooled analysis, using a random effect model in RevMan v.5.4. We performed a subgroup analysis based on a combined positive score (CPS) for programmed cell death ligand-1 (PDL-1) expression and tumor histology. Results: We included eight phase III RCTs (Jupiter-06, Checkmate 648, Keynote 590, ESCORT-1st, Orient-15, Checkmate 649, ESCORT-NEO, and ASTRUM-007), including 4131 patients with 2137 in group A (PD-1 inhibitor + chemotherapy) and 1994 in group B (placebo + chemotherapy, or chemotherapy). PD-1 inhibitors against EC included nivolumab, pembrolizumab, camrelizumab, sintilimab, toripalimab, and serplulimab. A total of 9.9% of patients were diagnosed with EAC, and 90.1% were ESCC. A pooled analysis showed significant achievement in ORR in group A compared to group B with an OR of 2.19 (CI: 1.77-2.69, p < 0.05, I² = 60%). In terms of OS benefit, group A led to a 29% reduction in death risk compared to group B (HR: 0.71, CI: 0.66-0.76, p < 0.05, I² = 0). Group A also showed a significantly reduced risk of disease progression compared to group B (HR: 0.62, CI: 0.54-0.70, p < 0.05, I² = 60%). Safety analysis revealed more TRAEs (OR: 1.93, CI: 1.43-2.60, p < 0.01, I² = 11%) and grade ≥3 AEs (OR: 1.34, CI: 1.08-1.67, p < 0.05, I² = 54%) in group A compared with group B. Sub-group analysis based on CPS revealed that patients with CPS ≥10 showed more OS (pooled HR: 0.59 vs 0.75) (p = 0.04) and PFS (pooled HR: (0.59 vs 0.64) (p = 0.18) benefits as compared to patients with CPS <10. Survival analysis between ESCC and EAC also exhibited statistically non-significant OS benefits (p = 0.28). Conclusions: PD-1 inhibitor plus chemotherapy as a first-line therapy in advanced EC, mainly in patients with CPS ≥10, showed improved antitumor efficacy in terms of superior ORR, OS, and PFS, with a manageable toxicity profile providing a benchmark for future studies.

Correlation between immune-related adverse events and clinical outcomes in patients treated with first-line nivolumab plus chemotherapy for advanced gastric or gastroesophageal junction cancer: A multi-center retrospective study in Japan.

439 Background: The CheckMate 649 trial and ATTRACTION-4 trial showed the efficacy of first-line nivolumab plus chemotherapy (Nivo-CT) for advanced gastric or gastroesophageal junction (GEJ) cancer. Recent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors were associated with survival benefit in patients with solid tumors. However, there were few data on correlation between irAEs and efficacy of first-line Nivo-CT for advanced gastric or GEJ cancer. Methods: This multi-center retrospective study included patients with histologically confirmed advanced gastric or GEJ adenocarcinoma who were started on first-line Nivo-CT between December 2021 and December 2023. We divided the patients into two groups according to occurrence of irAEs; those with irAEs (irAE group) or those without (non-irAE group) and assessed the efficacy in both groups. Efficacy was evaluated by overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Landmark analysis at 2 months after initiating Nivo-CT was performed to adjust effects of early progression or death, in which patients who had events up to 2 months were excluded. Results: A total of 271 patients were included (median age, 70 [range 18–85] years; male/female, 64/36%; performance status (PS) 0/1/2, 47/49/4%; primary tumor site gastric/GEJ, 90/10%; status unresectable/recurrent, 81/19%; histology intestinal/diffuse, 30/70%; PD-L1 CPS <1/1~5/>5, 15/33/53%). Median follow-up time was 11.3 (range 1-30) months, and 80 (30%) patients developed irAE. In the landmark analysis, the median PFS was 11.1 months in the irAE group and 7.2 months in non-irAE group (HR 0.70 [95%CI 0.50-0.97], p = 0.034), and the median OS was 22.5 months in the irAE group and 17.9 months in non-irAE group (HR 0.77 [95%CI, 0.50-1.17], p = 0.219). The ORR were 67.4% in the irAE group and 66.7% in non-irAE group (p = 0.934). Multivariate analysis indicated that PS ≥1 (HR 1.66 [95%CI, 1.20-2.30], p = 0.02), elevated ALP (HR 1.61 [95%CI, 1.13-2.27], p = 0.008), and absence of irAEs (HR 1.55 [95%CI, 1.08-2.22], p = 0.018) were associated with poor prognosis. The most frequent irAEs were pneumonitis (n = 16), and grade ≥3 irAEs were observed in 26 (9.6%) patients: pneumonitis (n = 6), hepatitis/hypophysitis (n = 5). Conclusions: Development of irAEs was associated with improved outcomes in advanced gastric or GEJ cancer patients receiving first-line Nivo-CT.

Development of a modified nutritional index model based on nutritional status and sarcopenia to predict long-term survival and chemotherapy benefits in elderly patients with advanced gastric cancer

BackgroundElderly patients with advanced gastric cancer have poor prognoses. This study aims to develop a prediction model for long-term survival after radical surgery and to identify patients who may benefit from chemotherapy. MethodsData from 555 elderly patients with advanced gastric cancer admitted to two medical centers from 2009 to 2018 were retrospectively analyzed. Sarcopenia was combined with the Controlling Nutritional Status (CONUT) score to create a modified nutritional index (mCONUT). Cox regression analyses were used to develop a novel nomogram prediction model (mCNS) that combined mCONUT, pN, and tumor size, and its performance was further verified both internally and externally. ResultsMultivariate Cox analysis revealed that tumor size, pN, and mCONUT were independent prognostic risk factors for overall survival (OS). The mCNS model showed good fit and high predictive value (AUC: training set 0.711; validation set 0.707), outperforming the pTNM model (p<0.05). To further investigate the association between the model and adjuvant chemotherapy, we categorized the model into two risk groups : a high-risk group and a low-risk group. Further analysis revealed that, in the low-risk group, the OS and recurrence-free survival(RFS) for patients receiving adjuvant chemotherapy was significantly better than that of those who did not receive chemotherapy (p=0.047,p=0.019). In the high-risk group, this result was not observed (p=0.120, p=0.053). ConclusionThe mCNS model has high predictive value in predicting long-term survival of elderly patients with advanced gastric cancer. Patients with mCNS-L were able to benefit from chemotherapy after laparoscopic radical gastrectomy.

Meta-analysis of phase II/III randomized controlled trials (RCTs) to evaluate the incidence of hand-foot skin reaction (HFSR) or palmar-plantar erythrodysesthesia (PPE) syndrome in patients with gastrointestinal (GI) cancers treated with fruquintinib.

117 Background: Fruquintinib is a selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3 blocks the angiogenesis associated with tumor proliferation. Recently, the US FDA approved fruquintinib as a third-line treatment for metastatic colorectal cancer (mCRC). As with any other novel cancer therapies, adverse events are always a concern and all patients should be monitored in order to early detect and appropriately treat any adverse events. This meta-analysis aims to assess the risk of HFSR or PPE syndrome in patients with GI cancers treated with fruquintinib. Methods: We conducted a comprehensive literature search using MEDLINE, EMBASE, and COCHRANE databases from inception through August 12th, 2024. Phase II/III RCTs utilizing fruquintinib in GI cancers mentioning HFSR or PPE as an adverse effect were included. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q-statistic. Random effects model was applied. Results: A total of 1872 patients, of whom 1131 (60%) received fruquintinib, from 3 phase III RCTs (FRESCO, FRESCO-2, FRUTIGA) and 1 phase II RCT were eligible for evaluation of HFSR or PPE incidence. FRESCO, FRESCO-2, and phase II trials involved patients with mCRC, they compared fruquintinib vs placebo. FRUTIGA trial involved patients with gastric or gastroesophageal junction adenocarcinoma, it compared fruquintinib + paclitaxel vs placebo + paclitaxel. The incidence of any-grade and high-grade HFSR or PPE was higher in the fruquintinib group compared to the placebo group, 27.93% vs 3.64% (RR, 7.64; 95% CI: 4.08-14.33; P&lt;0.00001), and 8.5% vs 0% (RR, 26.0; 95% CI: 6.42-105.29; P&lt;0.00001), respectively. In the mCRC subgroup analysis, the higher incidence of any-grade and high-grade HFSR or PPE in the fruquintinib arm was also statistically significant, 29.70% vs 2.55% (RR, 10.27; 95% CI: 5.59-18.88; P&lt;0.00001), and 8.45% vs 0% (RR, 19.34; 95% CI: 3.84-97.36; P=0.0003), respectively. Conclusions: This meta-analysis revealed increased incidence of any-grade and high-grade HFSR or PPE in patients with GI cancers including mCRC treated with fruquintinib. In the FRESCO trial, this association was also shown to confer survival benefit in Chinese patients with mCRC. Prompt identification and providing proper supportive care is crucial in managing this adverse event and ultimately, preserving the patients’ quality of life.

Fruquintinib combined with PD-1 inhibitors and chemotherapy in the first-line treatment of HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma (FDZL-FIX): A single-arm, open-label phase 2 study.

461 Background: For unresectable locally advanced or metastatic HER2-negative gastric cancer (GC), the combination of chemotherapy with immunotherapy, specifically PD-1 inhibitors, has emerged as a new standard of care in first-line treatment of advanced GC, but the patients’ outcomes remain poor. Early clinical studies investigating the combination of immunotherapy with anti-angiogenic drugs have demonstrated favorable efficacy. Therefore, it is worth exploring whether the addition of fruquintinib, a potent VEGFR-1,2,3 inhibitor, to the combination of PD-1 inhibitor and chemotherapy can further enhance the survival benefits for patients with unresectable locally advanced or metastatic HER2-negative GC. Methods: This is an open-label, single-center clinical study. The enrolled patients were all no less than 18 years old with HER2 negative locally advanced unresectable or metastatic gastric or gastrooesophageal junction adenocarcinoma, without any systemic anticancer treatment for advanced disease. Eligible patients received 6 cycles of combined first line treatment with fuquinitinib (4mg daily, d1-14, q3w, oral) combined with PD-1 inhibitor (sintilimab 200mg or nivolumab 360mg intravenously q3w) and chemotherapy (XELOX or SOX) regimen. The following maintenance treatment was fuquinitinib combined with PD-1 inhibitor and S-1/capecitabine until disease progression or intolerable toxicity. The primary endpoint was progress free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), duration of response (DoR), disease control rate (DCR) and safety. Results: At the cutoff date on Sep 18, 2024, a total of 27 patients were enrolled and received at least one dose of treatment. 23 patients had received the response evaluation, with an ORR of 60.9% (14/23; 95%CI 38.5-80.3) and DCR of 100% (23/23 95%CI 85.2-100.0). In the intention to treatment (ITT) population, the median PFS was 9.79 months (95% CI 5.29-NA). Safety profile indicated that 22.2% (6/27) experienced grade≥3 adverse events. The most common grade ≥ 3 adverse reactions mainly include neutropenia (7.4%, 2/27) and thrombocytopenia (7.4%%, 2/27). Conclusions: The combination of fruquintinib and chemotherapy with PD-1 blockade in the first-line treatment for unresectable locally advanced or metastatic HER2-negative GC had shown promising efficacy and acceptable safety profile. Enrollment in the trials is still ongoing. Clinical trial information: NCT06158919 .

Association between immune-related adverse events and prognosis after immune checkpoint inhibitor in hepatocellular carcinoma: A meta-analysis and systematic review.

566 Background: Immune checkpoint inhibitors (ICIs) have become the preferred treatment for unresectable hepatocellular carcinoma (HCC). Conflicting data exist regarding the prognostic value of immune-related adverse events (irAEs) in these patients. We aimed to explore potential the association between irAEs and prognosis in HCC patients treated with ICIs. Methods: We searched PubMed, Scopus, Web of Science, and CENTRAL databases for articles published from inception to June 2024 using keywords including ICI, HCC, and irAEs. Two reviewers independently screened studies for eligibility and relevant data. A random effects model was used for statistical analysis, and subgroup analysis was performed by the grade of irAEs. Results: Of 3,028 studies, 25 (n=4,116 patients) met criteria for inclusion. Atezolizumab plus bevacizumab was the most common treatment regimen (n=10 studies). About half (49.5%) of patients experienced irAEs. irAEs were associated with increased objective response rate (ORR) (pooled OR: 1.72; 95% CI: 1.36 – 2.19, I 2 =39%), higher complete response rate (pooled OR: 1.45; 95% CI: 1.21-1.74, I 2 =74%), and longer progression-free survival (PFS) (pooled HR: 0.66; 95% CI: 0.52-0.84, I 2 =71%). Although irAEs were associated with longer overall survival, this difference was not statistically significant (pooled HR: 0.83; 95% CI: 0.62 – 1.11, I 2 =73%). Subgroup analysis showed a survival benefit for patients with grade 1-2 irAEs (pooled HR: 0.50; 95% CI: 0.36-0.67, I 2 =0%) but not for those with grade 3-4 irAEs (pooled HR: 0.95; 95% CI: 0.24-3.72, I 2 =84%). Conclusions: The development of irAEs is associated with a favorable prognosis in HCC, including improved PFS and higher ORR. A survival benefit was noted in patients with mild irAEs, but not in those with severe irAEs. Future studies are needed to determine if a differential survival benefit relates to the continuation vs. discontinuation of ICI therapy.

Surgical treatment in patients with advanced gastrointestinal stromal tumours (GISTs) in second-line and later stages: A single-centre cohort study.

818 Background: Gastrointestinal stromal tumour (GIST) after imatinib treatment failure usually progresses rapidly with limited overall survival. Previous studies have suggested that surgery is beneficial for advanced GISTs in disease control to imatinib, but the role of surgery in &gt; = 2 line patients remains unclear. Methods: Imatinib-resistant patients with advanced GIST between May 2009 and Nov. 2023 were included. Surgical treatments included tumour reduction, radiofrequency ablation and TACE. The primary endpoint was overall survival (OS) and secondary endpoints were time to second-line treatment failure (TTF) and postoperative morbidity. To balance clinicopathological characteristics, 1:1 propensity score matching (PSM) was used. Results: A total of 242 patients with advanced GIST treated with 2nd-line or later drugs were included, including 125 in the surgical group and 117 in the non-surgical group. The median follow-up was 30.3 months. OS was significantly better in the surgical group than in the non-surgical group (pre-PSM: 51.7m vs 35.9m , p = 0.001; post-PSM: 50.8m vs 38.8m, p = 0.043). Univariate analysis showed that surgical treatment (HR 0.487, 95% CI 0.320-0.740, p = 0.001), age ≤60 years (HR 0.640, 95% CI 0.411-0.997, p = 0.049) and low tumour burden (HR 0.491, 95% CI 0.293-0.822, p = 0.007) were associated with prolonged OS. Multivariate analysis indicated that surgical treatment (HR 0.541, 95% CI 0.348-0.843, p = 0.007) and low tumour burden (HR 0.510, 95% CI 0.300-0.865, p = 0.012) were significantly associated with OS benefit. Patients (n = 84) who had surgical treatment during second-line treatment had longer TTF compared to patients (n = 158) who had TKI only (14.2m vs 8.1m , p = 0.003). There were 29 (14.8%) postoperative complications with Clavien-Dindo classification ≥3, including 5 deaths. Conclusions: Surgical treatment can provide a survival benefit for patients with second-line and later advanced GIST, but further studies are needed for a more detailed indication of the surgical population.

Characteristics and Outcomes of T1a Renal Cell Carcinoma Presenting with Metastasis

Objectives: The incidence of renal cell carcinoma (RCC) has been rising, largely due to increased incidental detection from widespread imaging. Although synchronous distant metastasis (SM) with a primary renal tumor measuring &lt;4 cm (cT1a) is uncommon, its presence may influence survival outcomes and the utility of cytoreductive nephrectomy. We sought to investigate clinical characteristics, metastatic patterns, treatments, and survival outcomes of patients with T1a RCC. Methods: All patients aged ≥18 years diagnosed with RCC between 2004 and 2019 were extracted from the National Cancer Database. The Cochran–Armitage test was used for trend analysis, while multivariable analyses were conducted to identify variables associated with SM and to assess the impact of cytoreductive surgery on mortality across isolated metastatic sites. Kaplan–Meier analysis was performed to compare survival outcomes. Results: A total of 263,911 individuals diagnosed with T1a RCC were analyzed in the study. Among them, 114,661 patients (43.4%) were classified as having cT1a tumor stage, and of these patients with cT1a RCC, 2275 (2.0%) exhibited SM. The proportion of SM cT1a was 3.39% in 2004 and 2.08% in 2019, with an Average Annual Percent Change (AAPC) of −0.037% (p = 0.830). The most common sites of metastasis were bone (59%), followed by lung (35%), liver (16%), and brain (12%). Resection of the primary tumor and receipt of systemic therapy were significantly associated with reduced mortality among all metastatic sites, especially in individuals with lung-only metastases (HR = 0.02, p = 0.013). Metastasectomy was associated with improved survival in patients with brain-only metastases (HR = 0.26, p = 0.006) but did not demonstrate the same benefit in patients with bone-, lung- or liver-only metastases. The worst 5-year OS rate was observed in cases with metastasis to multiple sites, whereas isolated metastases had similar survival rates (p &lt; 0.0001). Our findings are limited by retrospective study design. Conclusions: This comprehensive analysis of T1a RCC patients reveals that while synchronous metastasis is relatively uncommon (2.0%), it presents significant clinical challenges, with bone as the most common metastatic site, contrasting with the typical lung predominance in larger tumors. Primary tumor resection showed survival benefit in patients with isolated metastases, especially for lung-only metastasis. These findings highlight the heterogeneous nature of tumor biology in small renal masses and underscore the importance of tailored, multimodal treatment strategies for the effective management of SM T1a RCC.

Metformin use and pancreatic ductal adenocarcinoma outcomes: a narrative review.

Metformin is a diabetes medication with anti-mitotic properties. A narrative review was performed to investigate people using metformin and the risk of developing pancreatic ductal adenocarcinoma (PDAC) as well as survival outcomes in established PDAC. Relevant studies on metformin use and PDAC were retrieved from PubMed including observational studies on metformin and the risk of developing PDAC and survival outcomes in PDAC, and randomized controlled trials of metformin as a treatment in PDAC. Of the 367 studies searched, 26 studies fulfilled the criteria for this review. Metformin was not consistently associated with a reduced risk of developing PDAC. However, metformin use, especially higher cumulative doses, in some studies was associated with longer survival in patients with established PDAC, especially in the subgroup with resectable PDAC. Metformin use was not associated with longer survival in more advanced (non-resectable metastatic) PDAC. Metformin was not consistently associated with a reduced risk of developing PDAC. Metformin may be associated with overall survival benefits in patients with PDAC including the resectable PDAC subgroup but not in the metastatic PDAC subgroup. The evidence to date does not support the routine use of metformin as an adjuvant therapy for advanced PDAC.

Optimized Methods to Quantify Tumor Treating Fields (TTFields)-Induced Permeabilization of Glioblastoma Cell Membranes

Glioblastoma (GBM) is a lethal primary brain cancer with a 5.6% five-year survival rate. Tumor treating fields (TTFields) are alternating low-intensity electric fields that have demonstrated a GBM patient survival benefit. We previously reported that 0.5–24 h of TTFields exposure resulted in an increased uptake of FITC-dextran fluorescent probes (4–20 kDa) in human GBM cells. However, this approach, in which a fluorescence plate-based detector is used to evaluate cells attached to glass coverslips, cannot distinguish FITC-dextran uptake in live vs. dead cells. The goal of the study was to report the optimization and validation of two independent methods to quantify human GBM cell membrane permeabilization induced by TTFields exposure. First, we optimized flow cytometry by measuring mean fluorescence intensity at 72 h for 4 kDa (TTFields 6726 ± 958.0 vs. no-TTFields 5093 ± 239.7, p = 0.016) and 20 kDa (7087 ± 1137 vs. 5055 ± 897.8, p = 0.031) probes. Second, we measured the ratio of lactate dehydrogenase (LDH) to cell viability (measured using the CellTiter-Glo [CTG] viability assay); the LDH/CTG ratio was higher under TTFields (1.47 ± 0.15) than no-TTFields (1.08 ± 0.08) conditions, p &lt; 0.0001. The findings using these two independent methods reproducibly demonstrated their utility for time-dependent evaluations. We also showed that these methods can be used to relate the cell membrane-permeabilizing effects of the non-ionizing radiation of TTFields to that of an established cell membrane permeabilizer, the non-ionic detergent Triton-X-100. Evaluating carboplatin ± TTFields, the LDH/CTG ratio was significantly higher in the TTFields vs. no-TTFields condition at each carboplatin concentration (0–30 µM), p = 0.014. We successfully optimized and validated two cost-effective methods to reproducibly quantify TTFields-induced human GBM cancer cell membrane permeabilization.

Iterative Intraperitoneal Chemotherapy in Gastric Cancer Peritoneal Carcinomatosis.

Background/objectives: Despite the incremental improvement of survival with systemic therapy in metastatic gastric cancer (GC), the outcomes of patients with peritoneal carcinomatosis (PC) remain poor. The limited effectiveness of systemic therapy is attributed to the blood-peritoneal barrier and anarchic intra-tumoral circulation, which reduce the penetration of systemic therapy. Approaches that incorporate intraperitoneal (IP) chemotherapy, in addition to systemic therapies, may be a viable alternate strategy. Therefore, we provide a review of biology of gastric cancer peritoneal metastasis and evidence for bidirectional iterative IP chemotherapy in GCPC. Methods: A comprehensive search in PubMed, Scopus, Embase, Web of Science, Google Scholar, and ClinicalTrials.gov was performed to find the relevant articles and ongoing phase II/III clinical trials in iterative IP chemotherapy in GCPC. Results: Intraperitoneal (IP) chemotherapy leverages the blood-peritoneal barrier to allow for the administration of high concentrations of chemotherapy directly to the peritoneal metastases, with a significant reduction in the systemic toxicity and enhanced drug efficacy against peritoneal metastasis. This pharmacokinetic advantage of IP chemotherapy can be further enhanced by additional measures such as heat or aerosolization. There are three IP chemotherapy approaches, namely, heated intraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosolized chemotherapy (PIPAC), and normothermic intraperitoneal chemotherapy (NIPEC). Recent evidence suggests that iterative IP chemotherapy combined with systemic therapy may offer significant survival benefits for patients with peritoneal metastasis. Furthermore, bidirectional treatment approaches may also increase the chances of surgical resection and survival. Conclusions: IP chemotherapy plays a pivotal role in the management of gastric carcinomatosis, particularly in combination with cytoreduction in highly selected patients. The combination of systemic and regional control may increase the chances of surgical resection and may ultimately lead to significant survival benefits.

Machine learning-based prognostic modeling and surgical value analysis of de novo metastatic invasive ductal carcinoma of the breast.

Whether primary lesion surgery improves survival in patients with de novo metastatic breast cancer (dnMBC) is inconclusive. We aimed to establish a prognostic prediction model for patients with de novo metastatic breast invasive ductal carcinoma (dnMBIDC) based on machine learning algorithms and to investigate the value of primary site surgery. The data used in our study were obtained from the Surveillance, Epidemiology, and End Results database (SEER, 2010-2021) and the First Affiliated Hospital of Nanchang University (1st-NCUH, June 2013-June 2023). We used COX regression analysis to identify prognostic factors. We divided patients into training and validation groups and constructed Extreme Gradient Boosting (XGBoost) prognostic prediction model. In addition, we used propensity score matching (PSM), K-M survival analysis, and COX regression analysis to explore the survival benefit of patients undergoing primary lesion surgery. A total of 13,383 patients were enrolled, with 13,326 from SEER and 57 from 1st-NCUH. The results showed that XGboost had good predictive ability (training set C-index = 0.726, 1year AUC = 0.788, 3year AUC = 0.774, 5year AUC = 0.774; validation set C-index = 0.723, 1year AUC = 0.785.1, 3year AUC = 0.770, 5year AUC = 0.764), which has better predictive power than the Coxph model. We used Shiny-Web to make our model easily available. Furthermore, we found that surgery was associated with a better prognosis in dnMBIDC patients. Based on the XGboost, we can accurately predict the survival of dnMBIDC patients, which can provide a reference for clinicians to treat patients. In addition, surgery may bring survival benefits to dnMBIDC patients.

Trifluridine/Tipiracil (FTD/TPI) in Metastatic Colorectal Cancer in Hong Kong: A Territory-Wide Cohort Study.

Randomized phaseIII trials showed that using trifluridine/tipiracil (FTD/TPI) in patients with pre-treated metastatic colorectal cancer (mCRC) conferred survival benefit versus placebo. Here, we investigated the effectiveness and safety of FTD/TPI and sought to identify prognostic factors among the mCRC population in Hong Kong. A non-interventional, retrospective, multicenter cohort study enrolled patients with mCRC who received FTD/TPI in seven public hospitals in Hong Kong between 2016 and 2020. Overall survival (OS) was the primary endpoint; treatment duration and occurrence of neutropenia were secondary endpoints. We also performed a post hoc analysis to identify factors influencing OS and treatment duration. Overall, 456 patients were included (median age, 64.0years; 57.5% men). Approximately half (225/456; 49.3%) had RAS wild-type tumors; the median treatment duration was 12.4weeks (95% confidence interval [CI] 11.1-13.1). Median OS was 7.59months (95%CI 7.00-8.21). Overall, 289 (63.4%) patients developed neutropenia of any grade and 159 (34.9%) developed grade ≥ 3 neutropenia. Neutropenia at 1month occurred in 193 (43.1%) patients. The use of granulocyte colony-stimulating factor for neutropenia was reported for 42 (9.2%) patients. The development of neutropenia, absolute neutrophil count decrease of ≥ 2 grades in 1month, absence of liver metastasis, and RAS wild-type status were associated with significantly longer OS and, except for RAS wild-type status (not analyzed), longer treatment duration (p < 0.05 for all comparisons). Our data show that treatment with FTD/TPI offers survival benefits in patients with refractory mCRC in Hong Kong consistent with randomized controlled trials and other real-world studies. Furthermore, the prognosis in patients receiving FTD/TPI appears to be significantly better in those who develop neutropenia, with RAS wild-type status, or those without liver metastases, despite a higher rate of dose reduction in the real-world setting.

The Role of Cytoreductive Surgery in Platinum-Resistant Ovarian Cancer (PROC): A Systematic Review.

Platinum-resistant ovarian cancer (PROC) has limited therapeutic options, and the role of cytoreductive surgery (CRS) in improving survival outcomes remains uncertain. We performed a systematic review to evaluate the oncological benefit of CRS on PROC patients and the associated surgical morbidity and mortality. We followed a prospective protocol according to PRISMA guidelines. We searched PubMed, Medline, and Embase till October 2024. We used a "Population Intervention Comparator Outcomes (PICO)" framework. Our population included women with epithelial PROC who underwent CRS with/without chemotherapy. Our outcomes included overall survival (OS), progression-free-survival (PFS), post-operative morbidity and mortality and Quality of Life. Our search yielded 6590 citations; six studies (N = 155 patients) were included. There is limited evidence available on the role of CRS in PROC, with notable variation in reported outcomes and outcomes' measures; therefore, we were unable to perform quantitative synthesis. CRS demonstrated survival benefits in well-selected PROC patients, particularly those with limited, isolated recurrences, low tumour burden, and good performance status. Complete resection (R0) was associated with significantly longer OS/PFS compared to those who had suboptimal surgeries (R1/R2). CRS seems to extend survival in carefully selected PROC patients, especially those with limited disease spread and favourable surgical profiles. Nevertheless, CRS carries substantial surgical risks, and its benefits appear contingent upon achieving R0. Further prospective trials with standardised patient selection criteria are needed to define CRS's role in PROC. At present, CRS in PROC should be considered within a multidisciplinary approach in specialised gynaecological oncology centres, with the careful assessment of patient-specific risk factors and potential for R0 resection.

Alkaline phosphatase decline and pain response as predictors of overall survival benefit in patients treated with radium-223: a post hoc analysis of the REASSURE study.

Alkaline phosphatase (ALP) declines and pain responses can occur during radium-223 (223Ra) treatment, but their association with treatment outcomes is unclear. For patients with metastatic castration-resistant prostate cancer treated with 223Ra in the REASSURE study, we investigated whether ALP decline (Week 12) and/or pain response (during treatment) are associated with improved overall survival (OS). The Brief Pain Inventory-Short Form (BPI-SF) was used to assess pain at baseline and pain response (in patients with baseline BPI-SF score ≥2). Of 785 patients with baseline and Week 12 ALP measurements, 779 were eligible for the OS analyses. Overall, 80% of patients had an ALP decline. Median OS was longer in patients with than without an ALP decline (18.1 versus 14.2 months; HR 0.74; 95% CI 0.60-0.92). In patients with an ALP decline, there was no clear OS difference between those with versus without a pain response. For patients without ALP decline, median OS was longer in those with versus without a pain response (16.2 versus 10.9 months; HR 0.50; 95% CI 0.32-0.77). Decreases in ALP and/or pain during 223Ra treatment are associated with improved OS. This may help support clinical decisions. ClinicalTrials.gov identifier NCT02141438. Analyses from the radium-223 REASSURE global study suggest that declines in alkaline phosphatase and pain during treatment may predict longer survival in patients with advanced prostate cancer and may help doctors make decisions with their patients.

How Can We Improve the Survival of Patients with Colorectal Liver Metastases Using Thermal Ablation?

Thermal ablation has been widely used for patients with small colorectal liver metastases (CRLMs), even for resectable cases; however, solid evidence has been scarce. (1) Thermal ablation versus liver resection. Some propensity-score matching studies using patients with balanced baseline characteristics have confirmed less invasiveness and the comparable survival benefits of thermal ablation to liver resection. A more recent pivotal randomized controlled trial comparing thermal ablation and liver resection was presented during the American Society of Clinical Oncology 2024 meeting. Diameter ≤ 3 cm, ten or fewer resectable and ablatable CRLMs were assigned to thermal ablation or liver resection. No differences were observed in the overall survival and local and distant progression-free survival with less morbidity. (2) Combination of thermal ablation and liver resection. Four matching studies demonstrated comparable data between the combination and liver resection alone groups in the long-term survival and recurrence rates without increasing the postoperative complication rates. The selection of the two approaches depends primarily on the number, size, and location of the CRLMs. (3) Chemotherapy in combination with thermal ablation. A propensity-score matching study comparing thermal ablation ± neoadjuvant chemotherapy was conducted. The addition of neoadjuvant chemotherapy was an independent predictive factor for good progression-free survival without increasing morbidity. Two randomized controlled trials demonstrated that additional thermal ablation to systemic chemotherapy can improve the overall survival for initially unresectable CRLMs. (4) Conclusions. Thermal ablation can provide survival benefits for patients with CRLMs in various situations, keeping adequate indications.

Adjuvant taxane-based chemotherapy treatment in older patients with early breast cancer: A pooled analysis of five phase III trials from the Hellenic Oncology Research Group.

The use of taxanes in the adjuvant setting of early breast cancer (BC) confers survival benefits, however, their role in older patients merits further study. This retrospective pooled analysis of randomized controlled trials conducted by the Hellenic Oncology Research Group (HORG) aims to assess the efficacy and safety of taxane-based adjuvant chemotherapy in older women with BC. Five phase III trials containing a taxane, conducted by HORG between 1995 and 2013, were included in a patient-data pooled analysis. The primary endpoint was disease-free survival (DFS) at three years, whereas secondary outcomes included overall survival (OS) at five years and toxicity. A total of 3,026 randomized patients, of whom 701 (23%) were≥65years old (median age 69years; range 65-80), were included in the analysis. No statistically significant heterogeneity in survival was observed between older and younger patients. Within the cohort of older patients, taxane-based regimens were superior to 5-fluorouracil, epirubicin, and cyclophosphamide (FE75C) regimen in terms of three-year DFS (92.02% vs 77.17%; p<0.001) and five-year OS (94.38% vs 72.64%; p<0.001), respectively. A higher number of older patients discontinued treatment compared to younger patients (5.7% vs 2.9%; p<0.001), mainly due to toxicity (3.4% vs 1.8%; p=0.01). The incidence of grade 3-4 neutropenia (35.4% vs 29.8%; p=0.006) and thrombocytopenia (0.8% vs 0.3%; p=0.049) was higher for patients aged ≥65years compared to those aged <65years; however, there was no difference in terms of febrile neutropenia and non-hematologic toxicity. Taxane-based adjuvant chemotherapy offers significant survival benefits in older patients with BC, similar to younger patients, yet with increased toxicity.

Efficacy of pembrolizumab in microsatellite-stable, tumor mutational burden-high metastatic colorectal cancer: genomic signatures and clinical outcomes.

Pembrolizumab, an immune checkpoint inhibitor (ICI), shows significant survival benefits in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but its efficacy in microsatellite-stable (MSS) mCRC is limited. Although ICIs are effective in tumor mutational burden-high (TMB-H) solid tumors, the impact on MSS-TMB-H mCRC, a rare subset within MSS mCRC, remains unclear. We conducted a retrospective analysis using clinical and genomic data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) repository in Japan. Patients with MSS-TMB-H mCRC who underwent tissue-based comprehensive genomic profiling and were treated with pembrolizumab or other later-line therapies were included. Pembrolizumab's efficacy was compared with that of trifluridine/tipiracil (FTD/TPI) and regorafenib. Genomic profiles of MSS-TMB-H, MSI-H-TMB-H, and MSS-TMB-low (TMB-L) CRCs were analyzed across 71 cancer-related genes. Among 127 TMB-H mCRC cases treated with pembrolizumab in the C-CAT repository, 77 were MSS and 50 were MSI-H. Pembrolizumab showed significantly shorter time to treatment failure (TTF) and overall survival (OS) in patients with MSS-TMB-H mCRC compared with those with MSI-H-TMB-H mCRC [median TTF 2.0 versus 10.6 months; hazard ratio (HR) 4.79, 95% confidence interval (CI) 2.65-8.64, median OS 4.5 versus 33.6 months; HR 9.86, 95% CI 3.93-24.77, both P < 0.0001]. Among MSS-TMB-H mCRC patients, 19 received pembrolizumab, 73 received FTD/TPI (±bevacizumab), and 18 received regorafenib as their first later-line therapy. Pembrolizumab showed significantly shorter TTF and OS compared with FTD/TPI (median TTF 1.6 versus 4.1 months; HR 2.66, 95% CI 1.41-5.02, P= 0.0017, median OS 5.4 versus 13.8 months; HR 2.42, 95% CI, 1.09-5.38, P= 0.025). Genomic analysis of 6737 CRCs revealed that MSS-TMB-H CRCs harbored fewer pathogenic alterations than MSI-H-TMB-H CRCs but had a profile similar to MSS-TMB-L CRCs. Pembrolizumab may be less effective than FTD/TPI in later-line treatment of MSS-TMB-H mCRC, potentially due to genomic similarities between MSS-TMB-H and MSS-TMB-L CRC, suggesting the need for alternative therapeutic strategies in this subgroup.

Enfortumab vedotin plus pembrolizumab for previously untreated locally advanced or metastatic urothelial carcinoma: a cost-effectiveness analysis.

Both the antibody-drug conjugate (ADC) enfortumab vedotin (EV) and programmed death-1 inhibitor pembrolizumab have been shown to provide survival benefits in patients previously treated with locally advanced or metastatic urothelial carcinoma (la/mUC). Cost-effectiveness is necessary to consider whether the increased efficacy of the two therapies will lead to higher prices for first-line treatment of previously untreated la/mUC. To guide the choice of EV plus pembrolizumab or chemotherapy for patients with previously untreated la/mUC. The cost-effective analysis. A Markov model was developed to simulate the lifetime of patients with previously untreated la/mUC to assess the overall cost and efficacy of EV plus pembrolizumab and chemotherapy based on the EV-302/KEYNOTE-A39 trial. Primary outcomes included total cost, life-years (LYs), quality-adjusted LYs (QALYs), the incremental cost-effectiveness ratio (ICER), and incremental net health benefits at the USA and Chinese willingness-to-pay threshold of $150,000/QALY and $35,173/QALY, respectively. Model stability was examined through sensitivity and subgroup analyses. EV plus pembrolizumab and chemotherapy treatment regimens were associated with 2.07-2.16 and 1.04-1.06 QALYs with corresponding costs of $288,347-$532,362 and $24,773-$267,568, respectively. ICERs in the United States and China are $267,491/QALY and $254,339/QALY, respectively. The factors that most strongly influenced model outcomes in unidirectional sensitivity analyses were patient weight and the cost of EV. To achieve greater cost-effectiveness, EV costs would need to be reduced by over 75% and 10% in the United States and China, respectively. While first-line EV plus pembrolizumab has significant health benefits compared to chemotherapy for patients with previously untreated la/mUC, this regimen is not cost-effective at the current price in the United States or China.

Proteomic Response Predictor (PRP) For Beta Blocker Survival Benefit In Heart Failure Patients With Reduced Ejection Fraction

Proteomic Response Predictor (PRP) For Beta Blocker Survival Benefit In Heart Failure Patients With Reduced Ejection Fraction