Progression-free Survival Research Articles

The role of re-transurethral resection of bladder tumor in patients with TaHG non muscle invasive bladder cancer.

There is lack of evidence regarding the indication for re-transurethral resection of bladder tumor (reTURBT) for Ta high grade (HG) non-muscle invasive bladder cancer (NMIBC). This study aims to evaluate the oncological outcomes of patients with TaHG NMIBC to determine the benefit from performing reTURBT. We relied on a multicenter cohort of 317 TaHG NMIBC from 12 centers who underwent TURBT and a subsequent complete Bacillus Calmette-Guérin induction from 2009 to 2021. Kaplan Meier analyses estimated recurrence free survival (RFS) and progression free survival (PFS) according to reTURBT. Sub-analyses evaluated PFS in patients with multiple risk factors indicating necessity for reTURBT according to international guidelines (multifocality, size > 3cm, recurrent cancer, carcinoma in situ, lymph vascular invasion, histological variant, incomplete and absence of muscle layer at index TURBT). Multivariable cox-regression analysis predicted recurrence and progression. Of the 317 patients, 123 (39%) underwent reTURBT, while 194 (61%) did not. Residual disease was detected in 46% of cases, with a 3.2% upstaging rate. Median follow-up was 30months. The 3-year RFS was higher in patients who underwent reTURBT (79% vs. 58%, p < 0.001), but no significant difference was observed in PFS. ReTURBT reduced the risk of recurrence [multivariable hazard ratio: 0.45, 95% Confidence interval (CI) 0.29-0.71]. Among patients who did not undergo reTURBT, those with ≥ 2 risk factors had lower 3-year PFS (73% vs. 92%, p < 0.001) than those with 0-1 risk factor, whereas no difference in 3-year PFS was observed in patients who underwent reTURBT regardless of the number of risk factors (85% vs. 87%, p = 0.8). ReTURBT demonstrated efficacy in reducing recurrence among patients with TaHG NMIBC, yet its impact on progression remained uncertain. Our study underscores the importance of adhering to current international guidelines, particularly for patients with multiple risk factors indicating necessity for reTURBT.

Predictive value of pre-treatment circulating tumor DNA genomic landscape in patients with relapsed/refractory multiple myeloma undergoing anti-BCMA CAR-T therapy: Insights from tumor cells and T cells.

B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM. Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells. In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P=0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P=0.037), and higher percentages of CD8+ T cells (P=0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143ng/mL) and shorter progression-free survival (PFS) (P=0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143ng/mL), MM-driven high-risk mutations (including IGLL5 [P=0.004], IRF4 [P=0.024], and CREBBP [P=0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P=0.040) were independent risk factors for PFS. Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy. Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).

Combined Nabpaclitaxel pressurized intraPeritoneal aerosol chemotherapy with systemic Nabpaclitaxel-Gemcitabine chemotherapy for pancreatic cancer peritoneal metastases: protocol of single-arm, open-label, phase II trial (Nab-PIPAC trial)

Abstract Objectives Current therapies show limited efficacy against peritoneal metastases (PM) from pancreatic cancer. Pressurized intra-peritoneal aerosol chemotherapy (PIPAC) has emerged as a novel intraperitoneal drug delivery method. Recently, a dose-escalation study identified the safe dose of Nabpaclitaxel for PIPAC administration, an ideal intraperitoneal chemotherapy agent against pancreatic cancer. Combining systemic NabPaclitaxel-Gemcitabine with NabPaclitaxel-PIPAC may enhance disease control in pancreatic cancer patients with PM. Methods The Nab-PIPAC trial is a single-center, prospective, open-label, phase II study (ClinicalTrials.gov identifier: NCT05371223). Its primary goal is to evaluate the antitumor activity of the combined treatment based on Disease Control Rate (DCR) using RECISTv.1.1 criteria. Secondary objectives include feasibility, safety, pathological response, progression-free and overall survival, nutritional status, quality of life, pharmacokinetics of NabPaclitaxel-PIPAC, and PM molecular evolution via translational research. The treatment protocol consists of three courses, each with two cycles of intravenous NabPaclitaxel-Gemcitabine and one cycle of NabPaclitaxel-PIPAC, with standard metastatic pancreatic cancer doses for the former and 112.5 mg/m2 for the latter. Sample size follows Simon’s two-stage design: 12 patients in stage one and 26 in stage two (80 % power, 0.1 alpha). Results Partial results will be available after first stage enrollment. Conclusions This trial aims to determine the antitumor efficacy and safety of combining NabPaclitaxel-PIPAC with systemic NabPaclitaxel-Gemcitabine in pancreatic cancer patients with PM.

Phase II trial of multi-tyrosine kinase inhibitor ESK981 in combination with PD-1 inhibitor nivolumab in patients with metastatic castration-resistant prostate cancer.

Increasing the response rates of immune checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC) presents a significant challenge. ESK981 is a multi-tyrosine kinase and PIKfyve lipid kinase inhibitor that augments immunotherapeutic responses. In this phase II study, ESK981 was combined with the PD-1 blocking monoclonal antibody nivolumab to test for potentially improved response rates in patients with mCRPC who have progressed on androgen receptor (AR)-targeted agents and chemotherapy. Eligible patients received ESK981 orally once daily for five consecutive days, followed by a two-day break. Patients were also treated with nivolumab intravenously on Day 1 of each 28-day cycle. The primary endpoints were a 50% reduction in prostate-specific antigen (PSA50), and safety. Secondary endpoints included radiographic progression free survival (rPFS) and overall survival (OS). Additional investigations included whole exome sequencing in patients. Ten patients were enrolled. The maximum PSA decline from baseline of 14% was achieved in only one patient. Grade 3 treatment-related adverse events (AEs) included fatigue, anemia, and lymphopenia. There were no Grade 4 events. The median rPFS was 3.7 months (95% CI, 1.6-8.4). The median OS was 9.6 months (95% CI, 1.8-22.4). The study was terminated due to futility after 10 patients. Whole exome sequencing identified AR amplification in 63% of patients (5/8). ESK981 + nivolumab showed no antitumor activity in patients with AR-positive (AR+) mCRPC. Further evaluation of ESK981 combined with the PD-1 inhibitor nivolumab in AR + mCRPC patients is not warranted. (Trial registration: ClinicalTrials.gov NCT04159896. Registration date: November 12, 2019.).

Survival Outcomes of Patients with Primary Plasma Cell Leukemia in the Era of Proteasome Inhibitors and Immunomodulatory Agents: A Real-Life Multicenter Analysis.

In this study, we aimed to obtain real-life data on the use of antimyeloma agents, which significantly increase overall survival (OS) in multiple myeloma (MM) patients, in primary plasma cell leukemia (pPCL) patients with a poor prognosis. Data from 53 patients who were diagnosed with pPCL between 2011-2020 and who used at least one proteasome inhibitor (PI) and/or immunomodulatory (IMID) agent were analyzed retrospectively. Depending on the year of pPCL diagnosis, 20% leukocytes or ≥2×109/L plasma cells in the peripheral blood were used. The median age of the patients was 58 years, and 23 (43.4%) patients were over 65 years of age. For first-line treatment, PI or IMID alone was used in 31 (58.5%) patients, and PI and IMID were used simultaneously in 15 (28.3%) patients. Additionally, 21 (39.6%) patients received transplantation, and 13 (24.5%) patients received maintenance treatment. The median progression-free survival was 4 (1-42) months. When patients whose primary disease was refractory to first-line therapy were excluded, the duration of treatment was 6.5 months. The median OS was 15 months, with a median follow-up of 15 months. Only 7 (13.2%) of the patients were alive at the last follow-up visit. Those with higher beta-2 microglobulin levels and ISS stage 3 and nontransplant patients receiving first-line treatment had shorter OS (p=0.005, p=0.02 and p=0.008, respectively). Otherwise, the concomitant use of PIs and IMIDs, the addition of chemotherapy to induction therapy, and the response to induction therapy or maintenance therapy did not affect OS. In our study, as in previous similar studies, we could not see the increased survival trend in pPCL which is observed in MM. New studies are needed for pPCL patients, which is likely to increase with the new diagnostic criteria, based on current agents and information in MM.

Longitudinal Study of Transcriptomic Changes Occurring over Six Weeks of CHOP Treatment in Canine Lymphoma Identifies Prognostic Subtypes

The majority of canine lymphoma patients treated with the standard of care, the CHOP chemotherapy protocol, initially achieve remission but eventually relapse with a multi-drug-resistant phenotype. This study assesses gene expression profiles of canine lymphoma tumor cell populations using RNA-Seq data from 15 matched patient samples taken prior to treatment and again six weeks into treatment with CHOP. Two distinct clusters were present in the t-SNE dimensionality reduction of the gene expression profiles. There was a significant difference in progression-free survival (PFS) between the cluster groups, with a median of 43.5 days in a group of six patients and 185 days in another group of nine patients. Comparing the group with shorter PFS to the group with longer PFS, we identified 265 significantly enriched GO:BP terms in 3874 significantly up-regulated genes and 740 significantly enriched GO:BP terms in 3236 significantly down-regulated genes. Comparing the six-week timepoint against the initial timepoint, in the group with longer PFS, we identified 277 significantly enriched GO:BP terms in 413 significantly up-regulated genes and 222 significantly enriched GO:BP terms in 267 significantly down-regulated genes. In the group with shorter PFS, we only identified 27 significantly differentially expressed genes, for this comparison. We found DNA damage response genes to be enriched in the down-regulated genes in both comparisons. These results identify and characterize two transcriptionally distinct groups of canine lymphoma patients with significantly different responses to CHOP chemotherapy.

Different approach to M descriptor for future staging of oligometastatic disease in SCLC: A cross-sectional survival analysis.

This study aimed to investigate the impact of oligometastasis and the M descriptor on survival insmall cell lung cancer (SCLC). This multicenter, retrospectivestudy included patients with newly diagnosed extensive-stage SCLC(ES-SCLC) from 2010 to 2020. Subgroups: Group 1: single metastasis in a single organ, Group 2: 2-5 metastases in a single organ, Group 3: 6 or more metastases in a single organ, and Group 4: metastases in two or more organs. This classification was based on the 9th Staging-M descriptor. Three-year progression-free survival (PFS) and overall survival (OS) analyses were conducted. The mean age of the 439 patients was 62 ± 10years, and 89.5% of them were male. The mean PFS for Groups 1, 2, 3,4 was 10.7months (95% CI 8.9-12.5), 7.5months (95% CI 5.6-9.4), 4.3months (95% CI 2.9-5.7), and 5.4months (95% CI 4.7-6.1), respectively. PFS in Group 2 was significantly higher. The mean OS for Groups 1, 2, 3,4 was 13.3months (95% CI 11.2-15.3), 9.5months (95% CI 7.1-11.9), 7.1months (95% CI 4.5-9.7), and 6.9months (95% CI 6.0-7.9), respectively.OS in Group 1 was significantly higher. OS and PFS in the M1b group were significantly higher than in the M1c1 and M1c2 groups (p < 0.05) with no statistical difference between the M1c1 and M1c2 groups. There is no significant difference in survival between the M1c1 and M1c2 groups.In ES-SCLC, the number of metastases may be a more predictive factor for prognosis than the number of metastatic organs.

Busulfan and cyclophosphamide for autologous stem cell transplantation in patients with multiple myeloma after proteasome inhibitor and/or immunomodulatory drug treatment.

High-dose melphalan at 200mg/m2 (MEL-200) is the standard conditioning regimen before autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). Busulfan (BU) and cyclophosphamide (CY) can be used as alternatives when MEL is unavailable. However, most studies on BU/CY conditioning regimens were conducted before proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs) were available. This non-interventional comparative cohort study compared progression-free survival (PFS) between the MEL-200 and BU/CY in patients with MM treated with PIs and/or IMIDs. A total of 137 patients were analyzed (MEL-200,113 patients; BU/CY, 24 patients). The BU/CY group had a higher rate of PI and/or IMID use and very good partial response (VGPR) or complete remission (CR) at ASCT and post-ASCT maintenance. Median PFS was 29.7 and 46.8months in the MEL-200 and BU/CY groups, respectively. In the multivariate analysis, PFS was significantly better in the BU/CY group. International Staging System Stage I and VGPR or CR at ASCT were significantly associated with longer PFS. No treatment-related mortality was observed in either group by day 100. The BU/CY conditioning regimen may be a viable alternative to the MEL-200 regimen in patients with MM who undergo ASCT after treatment with PIs and/or IMIDs.

PET/computed tomography radiomics combined with clinical features in predicting sarcopenia and prognosis of diffuse large B-cell lymphoma.

The study aimed to assess the role of 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) radiomics combined with clinical features using machine learning (ML) in predicting sarcopenia and prognosis of patients with diffuse large B-cell lymphoma (DLBCL). A total of 178 DLBCL patients (118 and 60 applied for training and test sets, respectively) who underwent pretreatment 18F-FDG PET/CT were retrospectively enrolled. Clinical characteristics and PET/CT radiomics features were analyzed, and feature selection was performed using univariate logistic regression and correlation analysis. Sarcopenia prediction models were built by ML algorithms and evaluated. Besides, prognostic models were also developed, and their associations with progression-free survival (PFS) and overall survival (OS) were identified. Fourteen features were finally selected to build sarcopenia prediction and prognosis models, including two clinical (maximum standard uptake value of muscle and BMI), nine PET (seven gray-level and two first-order), and three CT (three gray-level) radiomics features. Among sarcopenia prediction models, combined clinical-PET/CT radiomics features models outperformed other models; especially the support vector machine algorithm achieved the highest area under curve of 0.862, with the sensitivity, specificity, and accuracy of 79.2, 83.3, and 78.3% in the test set. Furthermore, the consistency index based on the prognostic models was 0.753 and 0.807 for PFS and OS, respectively. The enrolled patients were subsequently divided into high-risk and low-risk groups with significant differences, regardless of PFS or OS (P < 0.05). ML models incorporating clinical and PET/CT radiomics features could effectively predict the presence of sarcopenia and assess the prognosis in patients with DLBCL.

Inferior Overall Survival After Haploidentical Donor Lymphocyte Infusions in Relapsed Myeloid Neoplasms.

Allogeneic hematopoietic stem cell transplantation (HSCT) effectively treats high-risk myeloid neoplasms, but relapses post-HSCT, particularly in acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS), pose significant challenges. Donor lymphocyte infusion (DLI) has been utilized, but its effectiveness, especially in haploidentical settings, remains insufficiently clarified, and graft-versus-host disease (GvHD) poses a substantial risk. In this retrospective cohort study, 57 patients with AML or MDS who received DLI after allogeneic HSCT at our center from 2002 to 2023 were analyzed. Herein, only preemptively or therapeutically applied DLI were included, and endpoints included overall survival (OS), progression-free survival (PFS), and GvHD incidence post-DLI. Median OS after DLI was 517 days, with a 1-year OS of 62.5%. Factors associated with longer OS included patient age, HLA-identical donor, post-HSCT treatment naivety, and preemptive DLI indication. Haploidentical DLI was associated with inferior OS compared to HLA-identical DLI; however, PFS and GvHD incidence post-DLI did not differ significantly. Our study findings indicate that OS rate is inferior in patients with relapsed AML or MDS treated with haploidentical DLI in comparison to those who received HLA-identical DLI. Given the limitations of haploidentical DLI, alternative strategies, such as higher cell doses or combination treatment approaches, warrant further investigation.

Prior antibiotics, proton pump inhibitors, and probiotics in patients with extensive stage small cell lung cancer treated with immune checkpoint blockade: A post-hoc analysis of the phase I/III IMpower 133 trial.

The potential impact of concomitant medications such as systemic antibiotics, proton pump inhibitors (PPIs), and probiotics in patients with extensive-stage small cell lung cancer (ES-SCLC) receiving first-line chemo-immunotherapy combinations remains unclear. We ran a post hoc analysis of the IMpower133 phase I/III trial, which randomized patients with ES-SCLC to receive carboplatin/etoposide with either atezolizumab or placebo for 4 cycles, followed by maintenance therapy. We included any systemic antibiotic/probiotic exposure within 42 days prior to treatment initiation and any PPIs treatment within 30 days prior to treatment initiation. We explored the potential prognostic impact of antibiotics, PPIs and probiotics across the atezolizumab/chemotherapy and placebo/chemotherapy arms including the multivariable interaction term between the treatment modality and antibiotics/PPIs/probiotics. The analysis included 198 patients in the atezolizumab/chemotherapy arm and 195 in the placebo/chemotherapy arm. Baseline clinic-pathologic features were well balanced between the two cohorts, with 17 (8.6%) and 14 (7.2%) patients on antibiotics, 43 (21.7%) and 55 (28.2%) on PPIs, and 3 (1.5%) and 5 (2.6%) on probiotics among the atezolizumab/chemotherapy and placebo/chemotherapy cohorts, respectively. Exposure to antibiotics, PPIs, or probiotics was not associated with overall survival or progression free survival in either cohort. Furthermore, interaction terms between these medications and treatment modalities were not statistically significant. Baseline use of antibiotics, PPIs or probiotics did not influence clinical outcomes in patients with ES-SCLC treated with first-line atezolizumab/placebo plus chemotherapy, suggesting that they may not have a notable impact on clinical outcomes and could be considered for use in this patient population when necessary.

Cost-Effectiveness of Pembrolizumab as First-Line Treatment in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer in the United States.

First-line treatment of persistent, recurrent, or metastatic (advanced) cervical cancer in patients who have a combined positive score (CPS) ≥ 1 with pembrolizumab + chemotherapy versus standard-of-care chemotherapy provides meaningful improvements in overall survival. We conducted a cost-effectiveness analysis from a US payer perspective. A societal perspective scenario was also considered, including productivity gains. The cost-effectiveness of pembrolizumab + chemotherapy versus chemotherapy was assessed using a state-transition model comprising the health states "pre-progression," "post-progression," and "death," with a 1-week cycle length and 50-year time horizon. Patient-level KEYNOTE-826 data informed the efficacy, safety, and health-related quality of life of pembrolizumab + chemotherapy versus chemotherapy at first-line and subsequent treatments. Real-world data were sought to cost subsequent treatments according to US clinical practice. Transition probabilities were derived from parametric survival models fit to time-to-progression, progression-free survival, and post-progression survival patient-level KEYNOTE-826 data. Sensitivity analyses explored the impact on outcomes from variables such as bevacizumab use. According to the state-transition model, pembrolizumab + chemotherapy extended mean life expectancy versus chemotherapy from 1.8 to 6.7 life-years. The mean gain of 4.9 life-years/patient was mostly caused by pembrolizumab delaying progression. Total discounted quality-adjusted life-years (QALY) were 5.0 and 1.3 per patient for pembrolizumab + chemotherapy and chemotherapy, respectively (mean gain: 3.7 QALY/patient). Pembrolizumab + chemotherapy had comparable safety outcomes to chemotherapy alone. Total costs incurred were US $320,247 (pembrolizumab + chemotherapy) versus US $105,446 (chemotherapy; mean incremental costs: US $214,801/patient). The incremental cost-effectiveness ratio of pembrolizumab + chemotherapy versus chemotherapy was US $58,446/QALY. Sensitivity analyses showed results were insensitive to bevacizumab use. Including productivity gains led to an incremental cost-effectiveness ratio of US $58,385 per QALY. Our model-based analysis suggests that first-line treatment of pembrolizumab + chemotherapy in advanced cervical cancer with a CPS ≥ 1 offers a substantial clinical benefit over standard-of-care chemotherapy alone and is cost-effective at a willingness-to-pay threshold of US $150,000. The approximate doubling of life-years and QALYs associated with pembrolizumab + chemotherapy represents a step improvement in the treatment of advanced cervical cancer. ClinicalTrials.gov Identification Number: NCT03635567.

“Repotrectinib: a promising new therapy for advanced non-small cell lung cancer”

Non-small cell lung cancer (NSCLC) is the major cause of cancer-related mortality worldwide, accounting for 84% of lung cancer cases. The newly FDA-approved kinase inhibitor, Repotrectinib (AUGTYRO), offers a promising option for treating advanced or metastatic NTRK/ROS1-positive NSCLC. Repotrectinib has demonstrated significant efficacy in clinical trials. Notably, the phase 1/2 TRIDENT-1 study showed impressive progression-free survival and intracranial activity in both TKI-naïve and pre-treated patients. With its high response rates and manageable side effects, Repotrectinib is set to play a significant role in treating ROS1+and NTRK+advanced solid tumors, highlighting the ongoing need for research and clinical application.

Limitations of outcome prediction based on interfractional volume changes of large (≥ 10cm3) brain metastases during fractionated gamma knife radiosurgery.

This study investigated the interfractional volume changes of large (≥ 10 cm3) brain metastases (BMs) during fractionated gamma knife radiosurgery (FGKRS) to assess its predictive value for tumor control outcomes. The patients who underwent FGKRS for large BMs between January 2017 and December 2022 in our center were reviewed. The interfractional volume change was defined as the disparity in tumor volume (TV) measured between the magnetic resonance images acquired on the first treatment day and those obtained after 2 or 3 fractions during the course of FGKRS. A total of 73 lesions in 70 patients with various primary pathologies were included. Over a median follow-up period of 11months (range 1-77), the tumor control rate was 63%. Initial TV (cm3) was associated with progression free survival (PFS) and overall survival (OS) in both univariate and multivariate analyses (p = 0.01). Interfractional TV changes revealed an increase in 13 (17.8%) lesions, no change in 14 (19.2%) lesions, and a decrease in 46 (63.0%) lesions, with a mean volume reduction of 5% ± 0.12. Three cut-offs (5%, 10% and 15% volume decrement) were established and patients were divided into two groups based on each reference point. However, there were no significant differences in PFS and OS between the two groups, irrespective of the chosen cut-off value used. Interfractional volume changes of large BMs were not found to be associated with tumor control outcomes. Neither significant interfractional volume reduction nor significant volume increase necessarily predicts the tumor control, making early close monitoring essential after FGKRS.

Impact of gastrectomy on efficacy and safety of second‐line chemotherapy patients with advanced gastric cancer: Exploratory analysis of two randomized phase III trials

AbstractAimsSecond‐line chemotherapy (SLC) improves survival in advanced gastric cancer (AGC). Although many patients receiving SLC have undergone gastrectomy, the impact of gastrectomy on SLC remains unclear.Patients and MethodsThe objective was to evaluate the impact of gastrectomy on SLC for AGC. A total of 290 eligible patients registered in two randomized phase III trials evaluating SLC for patients with AGC was classified into the prior gastrectomy group (PGG; n = 187) or the no gastrectomy group (NGG; n = 103). We compared overall survival (OS), progression‐free survival (PFS), overall response rate (ORR), disease control rate (DCR), and safety between these two groups. Adjusted OS and adjusted PFS were estimated using inverse probability of treatment weighting (IPTW).ResultsThe PGG had better performance status (p = 0.001), more prior platinum agent (p &lt; 0.001), and more frequent peritoneal metastasis (p = 0.006) than the NGG. The PGG had significantly better OS (13.8 vs. 9.3 mo; hazard ratio [HR]: 0.59; p &lt; 0.001) and PFS (4.7 vs. 2.8 mo; HR: 0.58; p &lt; 0.001) than the NGG. The PGG had significantly better adjusted OS (13.8 vs. 10.0 mo; IPTW HR: 0.66; p = 0.01) and adjusted PFS (4.3 vs. 3.2 mo; IPTW HR: 0.71; p = 0.027) than the NGG. No significant differences were observed in ORR and DCR. The incidence of Grade 3 or worse adverse events did not differ between the two groups except for a high incidence of anemia and diarrhea in the NGG.ConclusionPatients with previous gastrectomy are expected to have better survival outcomes when receiving second‐line irinotecan (IRI)‐based chemotherapy for AGC.

SGSM2 in Uveal Melanoma: Implications for Survival, Immune Infiltration, and Drug Sensitivity.

The abnormal expression of small G protein signaling modulator 2 (SGSM2) is related to the occurrence of thyroid cancer and breast cancer. However, the role of SGSM2 in uveal melanoma (UVM) is unclear. To elucidate this ambiguity, our study utilized bioinformatics analysis and experimental validation. The expression of SGSM2 was detected in UVM cell lines through quantitative real-- time PCR (qRT-PCR). We utilized the Cancer Genome Atlas (TCGA) database to assess the relationship between SGSM2 expression and clinical characteristics, as well as its prognostic significance in UVM. Furthermore, the study examined potential regulatory networks involving SGSM2 in relation to immune infiltration, immune checkpoint genes, microsatellite instability (MSI), and drug sensitivity in UVM. The study also examined SGSM2 expression in UVM single-cell sequencing data. SGSM2 was highly expressed in UVM cell lines. Moreover, elevated levels of SGSM2 in UVM patients were significantly linked to poorer overall survival (OS) (p < 0.001), progress- free survival (PFS) (p < 0.001), and disease-specific survival (DSS) (p < 0.001). Additionally, SGSM2 expression was identified as an independent prognostic factor in UVM patients (p < 0.001). SGSM2 was associated with several pathways, including the calcium signaling pathway, natural killer cell-mediated cytotoxicity, cell adhesion molecules (CAMs), and others. The study revealed that SGSM2 expression in UVM is linked to immune infiltration, immune checkpoint genes, and MSI. Additionally, a significant inverse correlation was observed between SGSM2 expression and the compounds GSK690693, TL-2-105, PHA-793887, Tubastatin A, and SB52334 in UVM patients. SGSM2 may not only serve as an important indicator for prognostic assessment. Still, it may also be a key target for the development of new therapeutic approaches, providing new perspectives on the treatment of UVM patients.

Clinical Benefits of Photodynamic Therapy Using Talaporfin Sodium in Patients With Isocitrate Dehydrogenase-Wildtype Diagnosed Glioblastoma: A Retrospective Study of 100 Cases.

Photodynamic therapy (PDT) with talaporfin sodium is an intraoperative local therapy administered after the surgical removal of malignant gliomas. However, its clinical efficacy in a large patient population has not been determined. To analyze the clinical outcomes and prognosis in isocitrate dehydrogenase (IDH)-wildtype glioblastoma patients treated with PDT. This retrospective study included patients with newly diagnosed IDH-wildtype glioblastoma treated at Kobe University Hospital between January 2013 and December 2022. PDT involves irradiation of the resection cavity with a 664-nm semiconductor laser after an intravenous infusion of talaporfin sodium. The main outcome measures were the recurrence patterns and survival times, which were compared between the PDT and non-PDT groups. Univariate and multivariate analyses were used to determine the prognostic factors. In addition, adverse events and prognostic factors in the PDT group were analyzed. A total of 44 and 56 patients were included in the PDT and non-PDT groups, respectively. The local recurrence rate was significantly lower in the PDT group than in the non-PDT group (51.3% vs 83.9%), whereas the distant recurrence and dissemination rates were significantly higher in the PDT group than in the non-PDT group (48.7% vs 16.1%). Two grade 3 adverse events were observed in the PDT group. The median progression-free survival and overall survival times were significantly longer in the PDT group than in the non-PDT group (progression-free survival: 10.8 vs 9.3 months, respectively, and overall survival: 24.6 vs 17.6 months, respectively). Multivariate analysis of the PDT groups revealed that younger age was an independent prognostic factor. PDT with talaporfin sodium provided effective local control with minimal adverse effects. The survival time of the patients treated with PDT was significantly longer than that of the patients who did not receive PDT. Therefore, a randomized controlled clinical trial on PDT is warranted.

The prognostic significance of MYC/BCL2 double expression in DLBCL in the genetic classification era.

Double expression (DE) is a World Health Organization-recognized adverse prognostic factor in diffuse large B-cell lymphoma (DLBCL). However, the prognostic value of DE in the genetic subtyping era and potential mechanisms remain to be explored. We enrolled 246 DLBCL patients diagnosed between December 2021 and September 2023 in a Jiangsu Province Hospital cohort and included 930 DLBCL patients from three published studies in an external cohort. Double-expression DLBCL (DEL) in the external cohort was mainly distributed in the OTHER subtype (42.0%), EZB subtype (28.3%), and MCD subtype (15.0%), whereas the MCD subtype exhibited the highest ratio of DEL. DEL was significantly related to unfavorable overall survival (OS) and progression-free survival (PFS) in DLBCL, but only in EZB and OTHER subtypes that DEL retained remarkably adverse impacts on survivals compared to non-DEL. We explored the prognostic value of clinical and genetic parameters in DEL patients and found only ST2 showed better OS than A53 in DEL patients, whereas the other subtypes showed no significant difference. DEL showed similarities with the MCD subtype in mutation profiles. Furthermore, RNA-sequencing analyses exhibited upregulation in tumor proliferation-related pathways in DEL patients, but downregulation in extracellular matrix organization, T-cell activation and proliferation, type II interferon production, and pathways associated with cell death might contribute to the poor outcomes of DEL patients.

Efficacy and safety of immune checkpoint inhibitors combined with chemotherapy or tyrosine kinase inhibitors in advanced endometrial cancer: A systematic review and meta-analysis.

The objective of this meta-analysis was to conduct a comprehensive assessment of the therapeutic effectiveness and safety profile of the combination of immune checkpoint inhibitors (ICIs) with either chemotherapy or tyrosine kinase inhibitors (TKIs) in the treatment of advanced-stage endometrial cancer (EC). This meta-analysis conducted a thorough literature search across PubMed, Cochrane Library, Embase, and Web of Science databases from their earliest records up to November 18th, 2023, identifying qualified randomized controlled trials (RCTs), cohort studies, and single-arm trials for inclusion in the analysis. The meta-analysis were performed to quantify and analyzed the evidence from the existing literature, focusing on outcomes including the objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS), progression-free survival (PFS), and adverse events (AE). A total of 13 studies were included. In terms of ICI combined with chemotherapy, the single-arm trials showed that ICI combined with chemotherapy was effective in improving the ORR, but the overall rate of AE was higher. The results based on RCT suggested that ICI combined with chemotherapy resulted in a longer PFS of 12-24 months and OS of 18-month compared to the control group in advanced EC. In terms of ICI combined with TKI, the pooled ORR was 39.0%, the pooled DCR was 79.9%, the pooled OS rate was 50.4%, and the pooled overall AE rate was 95.8%, the pooled grade ≥3 AE rate was 73.8%, the pooled median progression-free survival (mPFS) was 6.126 months, and pooled OS was 15.099 months in advanced EC. The integrative therapeutic approach combining (ICIs) with chemotherapy or (TKIs demonstrates notable clinical efficacy in advanced EC, which can prolong the survival and help to disease control. Nevertheless, it is imperative for clinicians to be vigilant regarding the potential for adverse reactions to emerge. In addition, more RCTs are needed to solidify this study's efficacy and safety further.

Durvalumab Following Chemoradiotherapy for Stage III Non-small Cell Lung Cancer: Differences in Survival Based on Age and Post-Progression Systemic Therapy.

Concurrent chemoradiotherapy (cCRT) followed by 1 year of the immune checkpoint inhibitor (ICI) durvalumab is standard of care for patients with unresectable stage III nonsmall cell lung cancer (NSCLC). The purpose of this study was to evaluate survival outcomes of (1) cCRT followed by durvalumab in patients older versus younger than 75 years of age and (2) post-progression treatment with ICI alone versus chemotherapy alone versus combined ICI and chemotherapy. Patients with unresectable stage III NSCLC treated between January 2018 and July 2023 with cCRT followed by durvalumab were identified retrospectively. Progression-free survival (PFS) and overall survival (OS) from ICI start were analyzed in three cohorts aged < 65, 65-74, and ≥ 75 years. Multivariable Cox proportional hazard regression modelling of factors associated with OS was undertaken. Logistic regression analysis identified risk factors of early durvalumab discontinuation for toxicity. Time from first salvage drug treatment to death (OS-2) was described. A total of 472 patients were analyzed: the proportions aged < 65, 65-74, and ≥ 75 years were 34.3%, 42.8%, and 22.9%, respectively. Odds of early durvalumab discontinuation was 2.2-fold greater in the oldest (versus youngest) cohort. Age associated differences in median PFS (26.7months, 20.3months, and 14.2months; p< 0.001) and OS (60.8months, 44.4 months, and 27.6 months; p< 0.001) were observed. On multivariable analysis, factors associated with shorter OS were age ≥ 75years (versus < 65), performance status 2/3 (versus 0/1), stage IIIC (versus IIIA), neutrophil to lymphocyte ratio (per 7.43 unit increase), Charlson comorbidity index (per 1 unit increase), tumoral PD-L1 expression < 1% (versus ≥ 50%, 1-49%, or unknown), and squamous histology (versus non-squamous). Of 264 patients with disease progression, 48.5% received subsequent drug therapy. Median OS-2 was longer with ICI alone (9.9 months) or ICI-chemotherapy (11.8 months) than platinum doublet chemotherapy (6.7 months.) For recurrences < 6 months from the last durvalumab infusion, OS-2 were similar across treatment groups. In the studied cohort, OS was significantly shorter for patients ≥ 75 years of age treated with cCRT followed by durvalumab compared to those < 65 years. Post-progression systemic therapy was associated with modest efficacy, underscoring the need for new therapies.