Solid Tumors Research Articles

Screening, identification, and diagnosis of malnutrition in hospitalized patients with solid tumors: A retrospective cohort study.

Malnutrition is common in hospitalized patients with cancer and adversely affects clinical outcomes. We evaluated the prevalence of malnutrition risk, dietitian-identified malnutrition (DIMN), and physician-diagnosed malnutrition (PDMN) at admission. This retrospective study included adults diagnosed with a stage I-IV solid tumor malignancy and admitted to Atrium Health Carolinas Medical Center from January 2016 to May 2019. Malnutrition risk was determined by a score ≥2 on the Malnutrition Screening Tool (MST) administered by a registered nurse during the intake process. Registered dietitian nutritionist (RDN) assessments were reviewed for DIMN and grade (mild, moderate, or severe). PDMN included malnutrition International Classification of Diseases, Tenth Revision codes in the discharge summary. Univariate models were estimated; multivariate logistic regression models identified associations between clinicodemographic factors and malnutrition prevalence with stepwise selection. A total of 5143 patients were included. Median age was 63 (range 18-102) years, 48% were female, 70% were White, and 24% were Black. Upper gastrointestinal (21%), thoracic (18%), and genitourinary (18%) cancers were most common. A total of 28% had stage IV disease. MST scores were available for 4085 (79%); 1005 of 4085 (25%) were at malnutrition risk. Eleven percent (n = 557) had malnutrition coded by a physician or documented by an RDN; 4% (n = 223) of these were identified by both clinicians, 4% (n = 197) by RDNs only, and 3% (n = 137) by physicians only. Malnutrition appears to be underdiagnosed by both RDNs and physicians. Underdiagnosis of malnutrition may have significant clinical, operational, and financial implications in cancer care.

Emerging Role of the p53 Pathway in Modulating Natural Killer Cell Mediated Immunity.

The p53 pathway plays an important role in role in cancer immunity. Mutation or downregulation of the proteins in the p53 pathway are prevalent in many cancers, contributing to tumor progression and immune dysregulation. Recent findings suggest that the activity of p53 within tumor cells, immune cells, and the tumor microenvironment can play an important role modulating natural killer (NK) cell-mediated immunity. Consequently, efforts to restore p53 pathway activity are being actively pursued to modulate this form of immunity. This review focuses on p53 activity regulating the infiltration and the activation of NK cells in the tumor immune microenvironment, which are illustrated in the Graphical Abstract for this review. Furthermore, impact of p53 and its regulation of NK cells on immunogenic cell death within solid tumors and the abscopal effect is reviewed. Finally, future avenues for therapeutically restoring p53 activity to improve NK cell-mediated anti-tumor immunity and optimize the effectiveness of cancer therapies are discussed.

Clinical characteristics and prognostic factors of epidermal growth factor receptor-mutated non-small cell lung cancer transformed into small-cell lung cancer after treatment

Objective: To analyze the clinical characteristics and prognostic factors of non-small cell lung cancer (NSCLC) patients with sensitive epidermal growth factor receptor (EGFR) mutations who developed small cell lung cancer (SCLC) transformation after treatment with EGFR tyrosine kinase inhibitors (TKI). Methods: We conducted a retrospective collection of clinical data for 21 patients with advanced EGFR mutant NSCLC who developed SCLC transformation after EGFR-TKI treatment at Beijing Chest Hospital, Capital Medical University from January 2015 to December 2021. The clinical characteristics were summarized and the prognosis analysis was conducted. Patients were followed up until February 2024. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in survival time (OS) between limited stage and extensive stage in transformed SCLC patients. Cox proportional hazards model was used to analyze the influencing factors of survival after SCLC transformation. Results: Among the 21 patients, there were 5 males and 16 females, with an age range of 33-74 years old [(58.9±2.6) years old]. All 21 patients were adenocarcinoma with sensitive EGFR mutations. There were 18 cases (85.7%) with EGFR gene 19del mutation, including 1 case of 19del+anaplastic lymphoma kinase (ALK) mutation, and 3 cases of L858R mutation. Among the transformed SCLC, there were 11 cases of pure SCLC and 10 cases of mixed SCLC (coexisting of adenocarcinoma and small cell carcinoma components). The median time from diagnosis of NSCLC to SCLC transformation was 12.0 months (95%CI: 7.6-16.3 months). Among the 21 cases of SCLC transformation, there were 13 cases with the extensive stage and 8 cases with the limited stage. Among them, 16 patients received systemic chemotherapy based on etoposide, of which 13 cases could be evaluated for efficacy, 11 cases could be calculated for PFS. Five cases had partial remission, 5 cases were stable, 3 cases had disease progression, and 3 cases cloud not be evaluated. The median progression free survival time (PFS) was 4.8 months (95%CI: 2.8-6.8 months). The median survival time (OS) after SCLC transformation in 21 patients was 10.6 months (95%CI: 7.0-14.2 months), with a median OS of 8.8 months (95%CI: 6.3-11.4 months) for patients with the extensive stage and 27.5 months (95%CI: 9.6-34.4 months) for patients with the limited stage, with statistically significant differences (P=0.002). Cox proportional hazards model analysis showed that the limited stage after SCLC transformation was a protective factor for OS (HR=0.32, 95%CI: 0.12-0.73, P=0.010). The median OS of 21 patients from the diagnosis of lung cancer was 24.9 months (95%CI: 13.0-36.7 months). Conclusions: NSCLC patients with SCLC transformation are all adenocarcinomas, and the proportion of EGFR19del mutations is relatively high. After SCLC transformation, the standard chemotherapy regimen for SCLC is generally used for treatment. The OS after SCLC transformation is related to the stage, and the prognosis is better in the limited stage.

Current Status of Immunotherapy in Management of Small Bowel Neuroendocrine Tumors.

This study aims to present the current landscape of immunotherapy in the management of small bowel neuroendocrine tumors and identify ongoing and future targets for improved response. Somatostatin analogs and mTOR inhibitors remain cornerstones of non-surgical treatment, and applications of PRRT in SBNET are promising. Several efforts to replicate the success of immunotherapies in other solid tumors have been attempted in SBNET, with limited responses observed with current immune targets, such as PD-1/PD-L1 and CTLA-4. Epigenetic analyses have suggested a potential role for methylation and histone acetylation in SBNET tumorigenesis that warrant greater exploration. While the incidence of SBNET continues to increase, the number of effective therapies is few. Further elucidation of targetable components of the SBNET immune microenvironment with greater modulatory effects is necessary to improve outcomes in this growing patient population.

Prognostic Evaluation of Conversion Therapy Following Hepatic Arterial Infusion Chemotherapy or Immunotherapy in Patients with Advanced or Transarterial Chemoembolization Unsuitable Intermediate-Stage Hepatocellular Carcinoma-A retrospective cohort study.

Patients with advanced-stage or intermediate-stage hepatocellular carcinoma (HCC) unsuitable for transarterial chemoembolization (TACE) had poor prognoses. Recent advancements in hepatic arterial infusion chemotherapy (HAIC) and immune checkpoint inhibitors (ICIs) have demonstrated higher tumor response rates, which improved overall survival (OS). HAIC achieves an OS rate of approximately 14.5-15.3 months with a 39.1-42.5% tumor response rate. In comparison, ICIs have a 12-14 month OS rate with a 26-33% tumor response rate. Given these promising responses, this study evaluates the efficacy of conversion therapy with curative intent following HAIC or ICIs, focusing on survival outcomes. We retrospectively analyzed 80 patients with advanced or TACE-unsuitable intermediate HCC. Patients completed two HAIC or four ICI cycles, followed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria imaging. Based on demographics, cirrhosis status, Barcelona Clinic Liver Cancer classification (BCLC) stage, treatment responses, and treatment modality, survival impacts were analyzed. OS was compared between HAIC and immunotherapy groups. The effect of conversion therapy with curative intent on survival outcomes was analyzed using a Cox regression model. Among the 80 patients, 26 achieved positive response (CR/PR) with HAIC or ICIs, and 9 of them subsequently underwent conversion therapy with curative intent. Key prognostic factors included Child-Pugh stage B vs. A (HR=2.21, p=0.041), BCLC stage C vs. B (HR=4.38, p=0.011), and elevated AFP levels (HR=5.02, p<0.001). Positive responders saw substantial survival benefits (HR=0.26, p=0.001). Patients undergoing conversion therapy exhibited significantly enhanced survival. Median OS was 13.58 months with standard therapy, while the curative intent surgery group did not reach the median OS (p=0.002). For CR/PR patients, 48-month survival was 75.0% for the curative surgery group versus 38.0% for standard treatment. Conversion therapy with curative intent following HAIC or ICIs might enhances survival in patients with advanced or TACE-unsuitable intermediate-stage HCC.

Pediatric cancer mortality: Analyzing early deaths and fatalities in a resource-limited tertiary care context.

Children with suspected cancer may succumb to their bad condition shortly after admission, even before a definitive diagnosis can be reached. We aimed to address the issue of delayed presentation and early deaths among children suspected of having cancer. We analyzed also the types and causes of mortalities across different tumor types. A retrospective review of reports from newly admitted patients between 2006 and 2010 at the pediatric oncology department of the South Egypt Cancer Institute (SECI) was done. Parameters included age, gender, diagnosis, symptoms, the interval between initial symptoms and the first visit to SECI, the duration from admission to death, and the cause of death. Among the 502 patients with confirmed malignancies, 238 (47.4%) succumbed. Causes of death were predominantly treatment-related mortalities (TRM) (66%). Mortalities within hematological malignancies were mainly TRM (81%), whereas solid tumors were primarily disease-related (70%), p <0.0001. The leading causes of TRM was infection (60%). About 5% of patients experienced early death within 48 hours after presenting to SECI. The mean duration from initial symptoms to the first SECI visit was 67 days, and the period from admission to death averaged 27 hours. Common initial symptoms included abdominal swelling (29.6%), or fever (26%). The leading causes of death were respiratory failure (29.6%), tumor lysis syndrome (22%), or septicemia (22%). Delayed presentation leading to early deaths poses a significant obstacle to the successful treatment of childhood cancers. Early diagnosis and improved supportive care are essential to enhancing the overall survival, particularly in patients with hematologigical malignancies.

TLR-4: a promising target for chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) affects a significant majority of cancer patients, with up to 80% experiencing this severe and dose-limiting side effect while undergoing anti-cancer treatment. CIPN can be induced by a variety of drugs commonly employed in the management of both solid tumors and hematologic cancers. The inadequacies in comprehending the pharmacological interventions associated with CIPN and the subsequent signaling pathways have significantly contributed to the disappointing outcomes of several drugs in clinical trials. Recent investigations in pain research have demonstrated a growing inclination toward addressing neuro-inflammation as a strategy for managing chronic pain conditions. Notably, toll-like receptor-4 (TLR-4) has emerged as a key player in immune system activation and is undergoing extensive research. In this review, we emphasize the potential role of TLR-4 in neuropathic pain, highlighting its promise as a target for CIPN treatment. Furthermore, we explore and analyse the intricate interplay between TLR-4, diverse immune cells, downstream pathways, and receptors within the context of CIPN. A comprehensive exploration of these interactions provides valuable insights into the central role of TLR-4 in CIPN development, paving the way for potential ground-breaking therapeutic approaches to alleviate this debilitating condition.

BRAF V600E-Mutant Acute Myeloid Leukemia: A Case Series and Literature Review of a Rare Entity

Background: Although BRAF V600E mutations are common in solid tumors and select hematologic neoplasms, they are reported less frequently in myeloid malignancies. Of the cases of BRAF V600E-mutant acute myeloid leukemia (AML) that have been described, most display monocytic morphology and concurrent KMT2A rearrangement. Strikingly, all cases have been associated with poor survival. Case Presentation: Here, we report two cases of AML, one diagnosed in an elderly male with metastatic lung adenocarcinoma and hepatocellular carcinoma and the other diagnosed in a young boy previously treated for B-cell acute lymphoblastic leukemia. Peripheral blood NGS revealed oncogenic mutations in BRAF p.V600E (VAF = 33%), TET2 p.M508Cfs*25 (VAF = 48%), TET2 p.C211* (VAF = 49%), ZRSR2 p.R295* (VAF = 71%), BRAF p.N581S (VAF = 6%), and EZH2 c.118-2A&gt;G, p.? (VAF = 4%) in case 1 and BRAF p.V600E (VAF = 1%) and KRAS p.G12A (VAF = 28%) in case 2. Cytogenetic workup revealed a complex karyotype in case 1 and an abnormal karyotype with non-clonal aberrations and KMT2A (MLL) rearrangement in case 2. Morphologically, both patients were found to have AML with monocytic features. The post-mortem examination of case 2 also revealed extensive solid organ infiltration, consistent with a monocytic leukemia. Both patients died within days of diagnosis, demonstrating the lethality of this molecular subgroup of AML. Conclusions: Our cases add to the literature, highlighting the poor prognosis of patients diagnosed with BRAF-mutant AML. Although it is uncertain whether the complex karyotype and somatic mutations observed in case 1 and KMT2A rearrangement and variants identified in case 2 may have either independently or cooperatively conferred a poor prognosis, we contend that additional comprehensive studies are needed to further understand the pathophysiology and prognosis of BRAF mutations in AML. We further posit whether patients with BRAF V600E-mutant AML may benefit from the combined use of BRAF inhibitors and/or RAS-pathway-targeting regimens, which are currently FDA-approved for the treatment of BRAF V600-mutant solid tumors and BRAF-mutant histiocytic neoplasms.

Efficacy and safety of pembrolizumab in patients with advanced urothelial carcinoma deemed potentially ineligible for platinum-containing chemotherapy: Post hoc analysis of KEYNOTE-052 and LEAP-011.

First-line pembrolizumab monotherapy is a standard of care for platinum-ineligible patients with advanced urothelial carcinoma (UC). No global standardized definition of platinum ineligibility exists. This study aimed to evaluate the efficacy and safety of pembrolizumab monotherapy in patients with UC who met various criteria for platinum ineligibility. Patients from KEYNOTE-052 and LEAP-011 deemed potentially platinum ineligible were pooled for this post hoc exploratory analysis as follows: group 1: Eastern Cooperative Oncology Group performance status (ECOG PS) 2; group 2: ECOG PS 2 and age ≥80 years, renal dysfunction, or visceral disease; and group 3: any two other factors regardless of ECOG PS. Patients received pembrolizumab 200 mg intravenously every 3 weeks. End points included objective response rate (ORR), progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1, by blinded independent central review, overall survival (OS), and safety. A total of 612 patients treated with pembrolizumab from KEYNOTE-052 (n=370) and LEAP-011 (n=242) were included; the median (range) follow-up was 56.3 months (51.2-65.3 months) and 12.8 months (0.2-25.1 months), respectively. For group 1, ORR was 26.2%, median PFS was 2.7 months, and median OS was 10.1 months. For group 2, ORR ranged from 23.5% to 33.3%, median PFS ranged from 2.1 to 4.4 months, and median OS ranged from 9.1 to 10.1 months. For group 3, ORR ranged from 25.7% to 27.9%, median PFS ranged from 2.1 to 2.8 months, and median OS ranged from 9.0 to 10.6 months. Treatment-related adverse event rates were consistent across groups. Frontline pembrolizumab has consistent antitumor activity and safety in patients with advanced UC categorized as potentially ineligible for platinum-based chemotherapy, regardless of the variable definitions of platinum ineligibility used.

Immune therapeutic strategies for the senescent tumor microenvironment.

Senescent cells can either to promote immunosuppressive tumor microenvironment or facilitate immune surveillance. Despite the revolutionary impact of cancer immunotherapy, durable responses in solid tumors, particularly in advanced stages, remain limited. Recent studies have shed light on the influence of senescent status within the tumor microenvironment (TME) on therapy resistance and major efforts are needed to overcome these challenges. This review summarizes recent advancements in targeting cellular senescence, with a particular focus on immunomodulatory approaches on the hallmarks of cellular senescence.

Effect of Hypoxia on Siglec-7 and Siglec-9 Receptors and Sialoglycan Ligands and Impact of Their Targeting on NK Cell Cytotoxicity

Background/Objectives: Tumor microenvironmental hypoxia is an established hallmark of solid tumors. It significantly contributes to tumor aggressiveness and therapy resistance and has been reported to affect the balance of activating/inhibitory surface receptors’ expression and activity on NK cells. In the current study, we investigated the impact of hypoxia on the surface expression of Siglec-7 and Siglec-9 (Sig-7/9) and their ligands in NK cells and tumor target cells. The functional consequence of Siglec blockage using nanoparticles specifically designed to target and block Sig-7/9 receptors on NK cell cytotoxicity was elucidated. Methods: CD56⁺ CD3− NK cells were isolated from PBMCs along with an NK-92 clone and used as effector cells, while MCF-7 and K562 served as target cells. All cells were incubated under normoxic or hypoxic conditions for 24 h. To assess Siglec-7 and Siglec-9 receptor expression, U937, NK-92, and primary NK cells were stained with PE-labeled antibodies against CD328 Siglec-7/9. Interactions between Siglec-7/9 and their sialylated ligands, along with their functional impact on NK cell activity, were evaluated using polymeric nanoparticles coated with a sialic acid mimetic. Immunological synapse formation and live-cell imaging were performed with a ZEISS LSM 800 with Airyscan at 10x magnification for 24 h. Results: Our data indicate that hypoxia had no effect on the expression of Siglec-7/9 receptors by NK cells. In contrast, hypoxic stress resulted in an increase in Siglec-7 sialoglycan ligand expression by a sub-population of NK target cells. Using polymeric nanoparticles coated with a sialic acid mimetic that binds both Siglec-7 and -9 (Sig-7/9 NP), we demonstrated that incubation of these nanoparticles with NK cells resulted in increased immunological synapse formation, granzyme B accumulation, and killing of NK target cells. These studies indicate that hypoxic stress may have an impact on NK cell-based therapies and highlight the need to consider the hypoxic microenvironment for tumor-specific glycosylation. Conclusions: Our findings point to the role of Siglec–sialylated glycan interactions in hypoxic stress-induced NK cell dysfunction and recommend the potential integration of the manipulation of this axis through the targeting of Siglecs in future cancer immunotherapy strategies.

Metastatic Melanoma to the Small Bowel and Colon: A Systematic Review of the Global Experience and Institutional Cohort Analysis Detailing a Rare Clinical Entity.

Cutaneous melanoma is among the most common solid tumors to metastasize to the gastrointestinal (GI) tract. Literature summarizing the clinical experience and features of this unique pathology is lacking. A systematic review of the available literature reporting clinically salient features of melanoma metastases to the small and large intestines was conducted. Additionally, we surveyed our institutional experience of surgically treated melanoma metastasis to the small bowel and colon. A descriptive analysis was performed. Kaplan-Meier curves with log-rank tests were used to analyze time-to-event intervals. Univariable and multivariable Cox logistic regression models were generated to identify predictors of survival. Over 100 studies including 1153 patients were included. GI metastases predominantly affected males, were in the small bowel/jejunum, equally presented as solitary and multiple lesions, and were generally not the first site of distant metastatic disease. The median time from primary lesion diagnosis to GI metastasis was 48 months. Analysis of our institutional cohort suggested that survival in patients receiving complete GI-specific surgical resection and immune checkpoint inhibitors (ICIs) was prolonged compared to palliative resection and without ICI therapy. Positive prognostic factors for survival following GI metastasis included fewer GI metastatic lesions, complete resection, and longer duration between primary tumor diagnosis and GI metastasis. GI metastases are a sign of advanced metastatic melanoma. Clinical suspicion of metastatic involvement in patients with a history of melanoma who develop any abdominal symptoms or anemia should remain high. Receipt of complete surgical resection and ICIs may prolong survival in disseminated melanoma.

Spleen-Targeted mRNA Vaccine Doped with Manganese Adjuvant for Robust Anticancer Immunity In Vivo.

The successful application of mRNA vaccines in preventing and treating infectious diseases highlights their potential as therapeutic vaccines for cancer treatment. However, unlike infectious diseases, effective antitumor therapy, particularly for solid tumors, necessitates the activation of more powerful cellular and humoral immunity to achieve clinical efficacy. Here, we report a spleen-targeted mRNA vaccine (Mn@mRNA-LNP) designed to deliver tumor antigen-encoding mRNA and manganese adjuvant (Mn2+) simultaneously to dendritic cells (DCs) in the spleen. This delivery system promotes DC maturation and surface antigen presentation and stimulates the production of cytotoxic T cells. Additionally, Mn2+ codelivered in the system serves as a safe and effective immune adjuvant, activating the stimulator of interferon genes (STING) signaling pathway and promoting the secretion of type I interferon, further enhancing the antigen-specific T cell responses. Mn@mRNA-LNP effectively inhibits tumor progression in established melanoma and colon tumor models as well as in a model of tumor recurrence after resection. Notably, the combination of Mn@mRNA-LNP with immune checkpoint inhibitors further enhances complete tumor suppression and prolonged the overall survival in mice. Overall, this "All-in-One" mRNA vaccine significantly boosts antitumor immunity responses by improving spleen targeting and immune activation, providing an attractive strategy for the future clinical translation of therapeutic mRNA vaccines.

A digital, decentralized trial of exercise therapy in patients with cancer

We developed and evaluated the Digital Platform for Exercise (DPEx): a decentralized, patient-centric approach designed to enhance all aspects of clinical investigation of exercise therapy. DPEx integrated provision of a treadmill with telemedicine and remote biospecimen collection permitting all study procedures to be conducted in patient’s homes. Linked health biodevices enabled high-resolution monitoring of lifestyle and physiological response. Here we describe the rationale and development of DPEx as well as feasibility evaluation in three different cohorts of patients with cancer: a phase 0a development study among three women with post-treatment primary breast cancer; a phase 0b proof-of-concept trial of neoadjuvant exercise therapy in 13 patients with untreated solid tumors; and a phase 1a level-finding trial of neoadjuvant exercise therapy in 53 men with localized prostate cancer. Collectively, our study demonstrates the utility of a fully digital, decentralized approach to conduct clinical trials of exercise therapy in a clinical population.

Sacituzumab Govitecan in Triple Negative Breast Cancer: A Systematic Review of Clinical Trials

Background/Objectives: Triple-negative breast cancer is difficult to treat due to the absence of hormone receptors and Her2neu. Sacituzumab govitecan is a new therapeutic approach that uses an antibody directed against the Trop-2 antigen present in solid epithelial tumors, linked to the active metabolite SN-38, similar to irinotecan, to specifically target cancer cells while minimizing damage to healthy cells. The objective of the present review was to evaluate the efficacy and safety of sacituzumab govitecan as a single treatment in patients with triple-negative breast cancer and to compare its results with the standard conventional chemotherapy regimen currently used in this disease. Methods: A systematic review of randomized clinical trials of sacituzumab govitecan was performed. The search was performed in Medline (PubMed), Web of Science, and Cochrane from September 2022 to January 2024. Results: Thirty-eight articles are included and evaluated according to inclusion and exclusion criteria corresponding to the two most relevant clinical trials, including specific analyses of cohorts and subgroup study arms within these trials. Data from more recent clinical trials are also reviewed. Conclusions: The efficacy results showed a significantly greater clinical benefit with sacituzumab govitecan compared to standard chemotherapy in patients with triple-negative breast cancer. This drug will become a treatment of substantial impact in future treatment guidelines for this type of cancer.

Tasurgratinib in patients with cholangiocarcinoma or gastric cancer: Expansion part of the first-in-human phase I study.

Fibroblast growth factor receptors (FGFRs) are a highly conserved family of transmembrane receptor tyrosine kinases with multiple roles in the regulation of key cellular processes. Specific FGFR mutations have been observed in several types of cancers, including gastric carcinoma and cholangiocarcinoma. Dose escalation data of 24 Japanese patients with solid tumors treated with Tasurgratinib (previously known as E7090), a potent, selective FGFR1-3 inhibitor, was reported in a phase I, first-in-human, single-center study. Based on the safety, pharmacokinetic, and pharmacodynamic profiles observed in this study, the recommended dose of 140 mg once daily was selected for the expansion part (Part 2), a multicenter expansion of the dose-finding study restricted to patients with tumors harboring FGFR gene alterations. Safety and preliminary efficacy were assessed in Part 2. Pharmacodynamic pharmacogenomic markers (serum phosphate, FGF23, and 1,25-(OH)2-vitamin D, circulating tumor DNA) and pharmacokinetic profiles were also evaluated. A total of 16 patients were enrolled in Part 2, six with cholangiocarcinoma and 10 with gastric cancer. The most common treatment-emergent adverse events were hyperphosphatemia, palmar-plantar erythrodysesthesia syndrome, and paronychia. Five partial responses (83.3%) in cholangiocarcinoma patients and one partial response (11.1%) in gastric cancer patients were observed; median progression-free survival was 8.26 months (95% confidence interval [CI] 3.84, not evaluable [NE]) and 3.25 months (95% CI 0.95, 4.86), and overall survival was 22.49 months (95% CI 6.37, NE) and 4.27 months (95% CI 2.23, 7.95), respectively, in the two groups. In conclusion, Tasurgratinib 140 mg has a tolerable safety profile with good clinical efficacy in patients with cholangiocarcinoma harboring FGFR2 gene rearrangements.

In Vitro Assessment of Thermo-Responsive Scaffold as a 3D Synthetic Matrix for CAR-T Potency Testing Against Glioblastoma Spheroids.

Chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated exceptional efficacy against hematological malignancies, but notably less against solid tumors. To overcome this limitation, it is critical to investigate antitumor CAR-T cell potency in synthetic 3D microenvironments that can simulate the physical barriers presented by solid tumors. The overall goal of this study was the preliminary assessment of a synthetic thermo-responsive material as a substrate for invitro co-cultures of anti-disialoganglioside (GD2) CAR-T cells and patient-derived glioblastoma (GBM) spheroids. Independent co-culture experiments demonstrated that the encapsulation process did not adversely affect the cell cycle progression of glioma stem cells (GSCs) or CAR-T cells. GSC spheroids grew over time within the terpolymer scaffold, when seeded in the same ratio as the suspension control. Co-cultures of CAR-T cells in suspension with hydrogel-encapsulated GSC spheroids demonstrated that CAR-T cells could migrate through the hydrogel and target the encapsulated GSC spheroids. CAR-T cells killed approximately 80% of encapsulated GSCs, while maintaining effective CD4:CD8 T cell ratios and secreting inflammatory cytokines after interacting with GD2-expressing GSCs. Importantly, the scaffolds also facilitated cell harvesting for downstream cellular analysis. This study demonstrated that a synthetic 3D terpolymer hydrogel can serve as an artificial scaffold to investigate cellular immunotherapeutic potency against solid tumors.

5-Fluorouracil combined with CalliSphere drug-eluting beads or conventional transarterial chemoembolization for unresectable hepatocellular carcinoma: a propensity score weighting analysis

This study aimed to assess the effectiveness and safety of 5-Fluorouracil (5-Fu) combined with conventional transarterial chemoembolization (cTACE) compared to 5-Fu combined with drug-eluting bead transarterial chemoembolization (DEB-TACE) using CalliSpheres for the treatment of unresectable hepatocellular carcinoma (HCC) using propensity score weighting methods. This retrospective analysis included 131 patients with HCC treated with 5-Fu combined with cTACE (5-Fu-cTACE group, n = 65) or DEB-TACE (5-Fu-DEB-TACE group, n = 66) at the Affiliated Hospital of North Sichuan Medical College from January 2019 to December 2022. Based on the baseline data and laboratory indicators, propensity score weighting was used to reduce confounding bias. Modified response evaluation criteria in solid tumors (mRECIST) were used to evaluate clinical efficacy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the disease control rate (DCR), objective response rate (ORR) and adverse events (AEs). PFS was assessed using Kaplan‒Meier analysis and Cox proportional hazards models. The ORRs at 1 month (M1) after treatment in the 5-Fu-DEB-TACE group and 5-Fu-cTACE group were 90.9% and 76.9%, respectively (P = 0.029), while at this time, the DCRs were 93.9% in the 5-Fu-DEB-TACE group and 90.8% in the 5-Fu-cTACE group (P = 0.494). At 3 months (M3) after treatment, the 5-Fu-DEB-TACE group had a higher ORR (84.8% vs. 56.9%, P < 0.001) and DCR (84.8% vs. 72.3%, P = 0.08). The ORR at 6 months (M6) was also higher in the 5-Fu-DEB-TACE group than in the 5-Fu-cTACE group (72.7% vs. 50.8%, P = 0.01). The median PFS after treatment with 5-Fu-DEB-TACE was longer than that after treatment with 5-Fu-cTACE (11 months vs. 6 months) (P = 0.004). Cox proportional hazards regression analysis indicated that 5-Fu-DEB-TACE (HR = 0.590, P = 0.044), Model for End-Stage Liver Disease (MELD) intermediate risk (HR = 2.470, P = 0.010), BCLC stage B (HR = 2.303, P = 0.036), BCLC stage C (HR = 3.354, P = 0.002) and ascitic fluid (HR = 2.004, P = 0.046) were independent predictors of PFS. No treatment-related deaths occurred in this study. The 5-Fu-DEB-TACE group had a greater incidence of abdominal pain (72.7% vs. 47.7%, P = 0.003). However, the incidence of postoperative elevated transaminase levels was higher in the 5-Fu-cTACE group (83.1% vs. 66.6%, P = 0.031). Subgroups analysis showed patients receiving 5-Fu-DEB-TACE have better PFS compared to those receiving 5-Fu-cTACE in the BCLC stage A group (P = 0.0093), BCLC stage B group (P = 0.0096), multifocal group (P = 0.0056), Child-Pugh stage A group (P<0.001), non- extrahepatic metastasis group (P = 0.022), non-vascular invasion group (P = 0.0093), and the group with a largest tumor diameter ≥ 5 cm (P = 0.0048). At M1, M3, and M6, patients with preserved liver function and in some cases of low tumor burden had higher Objective Response Rate (ORR) and Disease Control Rate (DCR) (P < 0.05). Compared with 5-Fu-cTACE, 5-Fu-DEB-TACE has superior therapeutic efficacy, prolongs PFS, and reduces hepatotoxicity. However, it is associated with an increased incidence of postoperative abdominal pain.

Seeing the Future of Lung Cancer Vaccination

It has been nearly fifteen years since the Food and Drug Administration (FDA) approved the first therapeutic cancer vaccine for solid tumors, namely Sipuleucel-T (Provenge®), marking a significant milestone in the treatment of metastatic castration-resistant prostate cancer [...]

Extramammary Paget's disease treated with of anti-programmed cell death protein 1 therapy after docetaxel therapy failure.

Extramammary Paget's disease (EMPD) is a rare skin cancer with no standard treatment for advanced-stage disease. Although docetaxel-based chemotherapy is common, no standard treatment exists. Pembrolizumab is approved for solid tumors with a high tumor mutation burden (TMB) and/or high microsatellite instability, and nivolumab was approved in Japan in February 2024 for unresectable advanced or recurrent epithelial skin malignancies. However, there is a lack of real-world data regarding the efficacy of anti-programmed cell death protein 1 (PD-1) therapy for EMPD. We present the case details of three EMPD patients treated with anti-PD-1 therapy after docetaxel treatment, with TMB values of 17.8, 14.3, and 5.0 mut/Mb, respectively, and we review similar reported cases. Even in the cases with a high TMB, the response to anti-PD-1 therapy was not sufficient. Most cases involve second-line or later treatments, so further research is needed to determine the precise effectiveness of anti-PD-1 therapy as a first-line treatment.