Background: Oral mucositis (OM) is a severe inflammatory and ulcerative condition of the oral mucosa commonly induced by chemotherapy. Photobiomodulation (PBM) therapy has been proposed for preventing and treating OM. However, the understanding of light interaction with biological tissues and the variability in light sources and protocols limit its widespread application. This study aimed to evaluate the impact of PBM on salivary nitrite levels, a marker of oxidative stress associated with inflammation and tissue damage. Materials and Methods: This prospective, randomized, double-blind clinical trial included 45 patients, evenly divided into three age- and sex-matched groups. Group 1 received basic oral care instructions prior to chemotherapy. Group 2 received these instructions plus PBM using a 650 nm intraoral diode laser. Group 3 received basic oral care instructions combined with PBM using both a 650 nm intraoral diode laser and a 980 nm extraoral diode laser. OM severity was assessed using World Health Organization criteria, and salivary nitrite levels were measured using the Griess reagent kit (Biotium®) according to the manufacturer's instructions 1 and 2 weeks after the first chemotherapy session. Results: Our study included 45 patients who were evenly distributed into three groups, matched for age, sex, tumor type, and type of chemotherapy. Significant differences in OM severity were observed among the groups at both 1 and 2 weeks (p = 0.000). Salivary nitrite levels also showed significant differences between groups at these time points (p = 0.00). Significant differences were found between the control group and both laser treatment groups, but no significant difference was noted between the two laser treatment groups. Conclusions: PBM effectively reduces OM severity, whether used intraorally alone or combined with extraoral application. This effect is likely due to PBM's ability to lower salivary nitrite levels, indicating reduced oxidative stress and inflammation.

Microsatellite instability-high (MSI-H)/mismatch repair deficiency (dMMR) is a biomarker for response to immune checkpoint inhibitors. We report updated results including objective response rate, progression free survival, and overall survival data with 5-year follow-up in recurrent platinum-resistant, MSI-H, endometrial cancer (EC) patients fully sequenced using whole exome sequencing (WES) and treated within a prospective phase II study with pembrolizumab (NCT02899793).

Poly(ADP-ribose) polymerase inhibitors (PARPis) are a class of agents targeting DNA damage repair that have become standard therapy for epithelial ovarian cancer (EOC) and multiple other solid tumors. In addition to targeting DNA damage repair, PARPis actively modulate antitumor immune responses, with efficacy being partially dependent on T cell activity. Here, we found that patient T cells sustain DNA damage during PARPi treatment, which reduces treatment efficacy. Leveraging paired pre- and posttreatment tumor samples from a clinical trial of patients with EOC treated with neoadjuvant niraparib as monotherapy, we showed that the PARPi caused DNA damage, slowed proliferation, and increased apoptosis in T cells, which we validated both in vitro and in mouse models. A genome-wide CRISPR (clustered regularly interspaced short palindromic repeats) knockout screen in primary human T cells identified PARP1 as the principal mediator of PARPi-induced T cell death. T cell-specific deletion of PARP1 or mutating Parp1 at its binding sites in transgenic mice led to reduced T cell DNA damage during PARPi treatment, resulting in improved efficacy of PARPis, alone or in combination with immune checkpoint inhibition. We then engineered PARPi-tolerant CAR T cells using cytosine base editing, which decreased PARPi-induced PARP1 trapping and led to reduced PARPi-induced DNA damage, resulting in superior antitumor efficacy in xenograft models compared with parental CAR T cells. This study highlights the relevance of PARPi-induced DNA damage to T cells and suggests opportunities to improve the efficacy of PARPis as monotherapy or in combination with immunotherapy.

Resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) poses a significant challenge to enhancing the efficacy of cancer treatments. Beyond the cellular mechanisms intrinsic to tumor cells, the modulation of the tumor immune microenvironment is crucial in dictating the responsiveness to pharmacological interventions. Thus, there is a pressing need to elucidate the intricate interplay between PARPi and antitumor immune responses and to develop an optimized combinatorial therapeutic approach. In this study, using matched tumor samples before and after neoadjuvant monotherapy with the PARPi niraparib in a prospective clinical trial (NCT04507841), we observed a significant increase in natural killer (NK) cell infiltration post-treatment. However, this was not accompanied by the expected enhancement in their cytotoxic functions. This observation underscores the necessity to optimize the antitumor potential of NK cells by enhancing their cytotoxic capabilities. Upon exposure to niraparib, tumor cells, particularly those with wild-type EGFR, exhibited a pronounced upregulation of human leukocyte antigen G (HLA-G), an immune checkpoint impeding NK cell functions. Niraparib promotes EGFR internalization, which in turn diminishes AKT/mTOR signaling, leading to the increased transcriptional activity of the transcription factor EB (TFEB) and subsequent enhancement of HLA-G expression. The combination of niraparib with HLA-G blockade not only augmented NK cell-mediated tumor lysis in vitro but also synergistically inhibited tumor growth in humanized patient-derived xenograft models. Collectively, our results shed light on a previously unrecognized immune evasion mechanism and offer a compelling argument for the integration of HLA-G blockade with PARPi in cancer therapy.

Patients with melanoma progressing on immune checkpoint blockade may benefit from adoptive transfer of tumor-infiltrating lymphocytes (TIL).

Background Transarterial chemoembolization (TACE) is regarded as the first-line treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC). However, the optimal chemotherapeutic agent loaded in TACE remains controversial. Purpose To compare the efficacy and safety of idarubicin and epirubicin as loaded drugs in drug-eluting bead (DEB)-TACE in patients with BCLC stage B HCC. Materials and Methods In this open-label, phase IV trial, patients with BCLC stage B HCC were recruited from four centers from August 2020 to October 2022 and randomly assigned (at a one-to-one ratio) to undergo idarubicin DEB-TACE or epirubicin DEB-TACE. The primary end point was progression-free survival (PFS), which was measured from the time of randomization to the time of progression or death from any cause. The efficacy analysis was conducted on an intention-to-treat basis, and only participants who received treatment were included in the safety analysis. Results A total of 239 participants (median age, 57 years; IQR, 50-66 years; 210 male) were randomly assigned to the idarubicin group (n = 120) or the epirubicin group (n = 119). The primary analysis cutoff for PFS was March 1, 2023, with 167 events observed (70%; idarubicin group, 85 events; epirubicin group, 82 events). The median PFS was 10.8 months and 8.7 months in the idarubicin and epirubicin groups, respectively (hazard ratio [HR], 0.61; 95% CI: 0.44, 0.84; P = .002). The HR for median overall survival (OS) was 0.53 (95% CI: 0.31, 0.88), with OS rates of 81.5% and 77.3% at 12 months and 71.8% and 54.0% at 24 months for the idarubicin and epirubicin groups, respectively. The objective response rates were 70.8% and 57.1% for the idarubicin and epirubicin groups, respectively (P = .03). There was no evidence of a between-group difference in incidence of adverse events, including hematologic toxicity. No treatment-related deaths were observed. Conclusion Idarubicin DEB-TACE increased survival in participants with BCLC stage B HCC, without an increase in the incidence of any adverse events. Clinical trial registration no. ChiCTR2000034758 © RSNA, 2025 Supplemental material is available for this article.

In the phase 3 EMPOWER-Lung 1 study, first-line cemiplimab monotherapy provided significant survival benefit versus chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. This exploratory subgroup analysis investigated the clinical outcomes of cemiplimab treatment in patients with advanced NSCLC with brain metastases.

Treatment of advanced mycosis fungoides (MF) and Sézary syndrome (SS) is a challenge. In this international, multicenter, open-label phase II trial, we assessed the efficacy and safety of anti-PD-L1 atezolizumab in stage IIB-IV refractory/relapsed MF and SS.

To evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary antitumour activity of AMG 404, a fully human IgG1 monoclonal antibody targeting programmed cell death-1, in patients with advanced solid tumours.

Anti-PD-1 monotherapy has shown limited clinical efficacy in patients with relapsed/refractory acute myeloid leukemia (r/r AML). Our study aimed to analyze the effectiveness and safety of combining tislelizumab with a hypomethylating agent (HMA) plus CAG regimen in treating patients with r/r AML, with an increased sample size and in comparison, with a historical control group for more reliable data support (ClinicalTrials.gov identifier NCT04541277).

Initial results of this study, reported after a median follow-up close to 4 years, demonstrated improved time to initiation of new treatment (TTNT) for patients with advanced stage, asymptomatic, low tumour burden follicular lymphoma who received early rituximab monotherapy when compared with watchful waiting. Given the long natural history of follicular lymphoma, the trial was extended to further assess TTNT with longer follow-up. Mature data are presented here.

SANET-ep (NCT02588170) and SANET-p (NCT02589821) demonstrated the efficacy and safety of surufatinib versus placebo in patients with advanced extra-pancreatic and pancreatic neuroendocrine tumours (NETs). Here, we present a pooled analysis of final overall survival (OS) from two randomised phase 3 studies.

The purpose of this study was to evaluate the benefits of the Baduanjin exercise and nutrition intervention on Cancer-related fatigue (CRF) in elderly lung cancer patients undergoing chemotherapy.

The β2 common integrin subunit CD18 is essential for leukocyte-endothelial adhesion and extravasation to inflamed or infected tissue. Damaging variants in ITGB2, which encodes CD18, cause leukocyte adhesion deficiency type I (LAD-I), an inborn error of immunity that leads to frequent life-threatening infections and a high risk of death among affected children. Allogeneic hematopoietic stem-cell transplantation (HSCT) represents a curative treatment but is limited by donor availability, a high incidence of graft-versus-host disease, and graft failure.

RBN-3143 is an inhibitor of PARP14 in development for inflammatory diseases. Multiple assessments were conducted to evaluate the clinical pharmacology properties of RBN-3134. A randomized, double-blind, placebo-controlled study assigned healthy volunteers (HVs) to single ascending doses (SADs) (25-1000 mg) or multiple ascending doses (MADs) (150, 300, and 500 mg twice daily [BID] for 14 days) of RBN-3143 or placebo. An open-label, randomized, 3-period, cross-over study evaluated the effects of food and pantoprazole (40 mg once daily [QD]) on the pharmacokinetics of RBN-3143 (500 mg), and a pharmacokinetic drug-drug interaction study with oral midazolam (2 mg) determined whether RBN-3143 (300 mg BID for 14 days) is an inducer of cytochrome P4503A4 (CYP3A4). The most common treatment-related treatment-emergent adverse events in subjects taking RBN-3143 were headache, nausea, vomiting, and elevated serum creatinine. In the SAD, RBN-3143 Cmax and AUCinf increased with dose, and Tmax was 2 hours. RBN-3143 was cleared from plasma with an apparent terminal half-life ranging from 3 to 11 hours. In the MAD, Cmax and AUCinf increased 1.5- and 1.6-fold, respectively, following 14 days of 150, 300, and 500 mg BID dosing. Dosing of RBN-3143 with food resulted in higher Cmax and AUCinf ratios of 1.74 and 1.42, respectively. Coadministration with pantoprazole did not impact RBN-3143 exposure. RBN-3143 was an inducer of CYP3A4 in most but not all subjects, with mean midazolam Cmax and AUCinf ratios of 0.92 and 0.88, respectively. The clinical pharmacology properties of RBN-3143 in HVs support further development for inflammatory diseases.

Maintenance olaparib demonstrated clinical activity for progression-free survival in patients without a germline BRCA1 and/or BRCA2 mutation (non-gBRCAm) who had platinum-sensitive relapsed ovarian cancer in the phase IIIb, open-label, single-arm, non-comparator, international OPINION trial (NCT03402841). We report final overall survival (OS; secondary endpoint), prespecified secondary endpoint updates and ad hoc OS analysis by homologous recombination deficiency (HRD) and somatic BRCAm (sBRCAm) status.

Neoadjuvant treatment of bladder cancer is evolving, with immunotherapy demonstrating promising activity. PARP inhibition combined with immune activation has been proposed as a synergistic strategy. We conducted a comprehensive molecular characterization of tumors treated with this combination in the neoadjuvant setting to provide crucial results for rational development.

Low-dose tamoxifen 5 mg/day (babytam) for 3 years can decrease the incidence of new breast cancer events in women with breast intraepithelial neoplasia by 42% with limited toxicity, which provides a new treatment option for these disorders. However, predictive biomarkers of babytam efficacy are lacking. We studied whether baseline levels of insulin-like growth factor-1 (IGF-I), IGF-binding protein-3 (IGFBP-3), estradiol, and sex hormone-binding globulin (SHBG) and their ratios predict babytam efficacy on breast cancer events in a preplanned secondary analysis.

Among patients with mismatch repair-deficient (dMMR), locally advanced rectal cancer, neoadjuvant checkpoint blockade eliminated the need for surgery in a high proportion of patients. Whether this approach can be extended to all early-stage dMMR solid tumors, regardless of tumor site, is unknown.

Peripheral T-cell lymphoma (PTCL) is an aggressive malignancy with limited treatment options and poor prognosis, particularly for relapsed or refractory (r/r) patients. HH2853, a novel dual inhibitor of EZH1/2, has previously demonstrated clinical benefits in solid tumors. Here, we report safety and efficacy data from a phase Ib trial of HH2853 in r/r PTCL.