Biliary tract cancers (BTCs) harbor an immunosuppressed tumor microenvironment and respond poorly to PD-1/PD-L1 inhibitors. Bevacizumab (anti-vascular endothelial growth factor) plus chemotherapy can promote anticancer immunity, augmenting response to PD-L1 inhibition.

The iPocc trial, a randomized, global phase 3 study that compared intraperitoneal (IP) and intravenous (IV) carboplatin with dose-dense paclitaxel chemotherapy in epithelial ovarian cancer (EOC) patients, demonstrated improved progression-free survival in patients who received IP chemotherapy. The present study aimed to investigate the role of preexisting tumor immunity in the clinical outcomes of patients receiving IP chemotherapy.

Genetics may influence symptoms experienced by breast cancer survivors (BCS) by moderating the effects of stress-reducing interventions, including the Mindfulness-Based Stress Reduction (MBSR(BC)) program, to reduce symptom severity. As part of a larger clinical trial, the aim of this study was to evaluate genetic variants as moderators of MBSR(BC) on improvements among BCS in cognitive functioning and symptoms.

Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and targetable genomic alterations. Two cohorts of patients with cyclin-dependent kinase inhibitor 2A (CDKN2A)-mutated tumors treated with palbociclib are reported: one with head and neck cancer (HNC) with both squamous and nonsquamous cell histologies, and one with histology-pooled (HP) cancers.

Mismatch repair-deficient (dMMR) endometrial cancer (EC) is an inflamed phenotype with poor outcomes when meeting high-risk criteria and limited treatment options in the adjuvant setting. We report protocol-prespecified subgroup analysis of patients with dMMR tumors from the phase III ENGOT-en11/GOG-3053/KEYNOTE-B21 study (ClinicalTrials.gov identifier: NCT04634877) in newly diagnosed, high-risk EC after surgery with curative intent. Patients were randomly assigned to pembrolizumab 200 mg or placebo (six cycles) plus carboplatin-paclitaxel (four to six cycles) once every 3 weeks, then pembrolizumab 400 mg or placebo once every 6 weeks (six cycles), respectively. MMR status was a stratification factor. Patients received radiotherapy at investigator discretion. Investigator-assessed disease-free survival (DFS) was a primary end point. No formal hypothesis testing was performed for subgroup analysis. In the intention-to-treat population, 141 patients in the pembrolizumab arm and 140 in the placebo arm had dMMR tumors. At this interim analysis, hazard ratio for DFS favored pembrolizumab (0.31 [95% CI, 0.14 to 0.69]); median DFS was not reached in either group. Two-year DFS rates were 92.4% (95% CI, 84.4 to 96.4) and 80.2% (95% CI, 70.8 to 86.9), respectively. No new safety signals occurred. Longer-term follow-up of outcomes will be evaluated at final analysis. Preplanned subgroup analysis on the basis of the study's stratification factors suggests that pembrolizumab plus chemotherapy improves DFS and is clinically relevant for patients with dMMR tumors in the curative-intent setting.

Urinary tumor DNA (utDNA) profiling identifies mutations associated with urothelial carcinoma and can be used to detect minimal residual disease (MRD). We evaluate the utility of utDNA profiling to predict treatment failure in bacillus Calmette-Guérin-unresponsive high-grade (HG) non-muscle-invasive bladder cancer (NMIBC) treated with nadofaragene firadenovec.

In a randomized phase II trial (AMLSG 14-09, NCT00867672) of elderly, newly diagnosed AML patients, ATRA combined with decitabine (DEC) significantly improved the overall response rate (ORR) and survival also in patients with adverse-risk genetics, without adding toxicity. We performed a post hoc analysis to determine the predictive impact of TP53 status. Despite a nominally higher ORR, the clinically meaningful survival benefit when adding ATRA to DEC was diminished, but not completely negated, in TP53-mutated patients. Indeed, 2 out of 14 TP53-mutated patients (14%) randomized to a DEC + ATRA-containing regimen lived for > 36 months. Further studies of ATRA combined with hypomethylating agents appear warranted in non-M3 AML patients ineligible for HMA/venetoclax therapy. Trial Registration: ClinicalTrials.gov identifier: NCT00867672.

Zorifertinib (AZD3759), an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with high blood-brain barrier penetration capability, demonstrated promising intracranial and systemic antitumor activity in phase 1 and 2 studies in central nervous system (CNS)-metastatic patients.

To investigate the efficacy of Longteng Tongluo recipe (, LTTL) combined with three-step analgesia for the treatment of lung cancer pain, and the changes in serum miRNA expressions before- and after treatment with LTTL and its correlation with lung cancer pain. The possible mechanism underlying LTTL effects on the treatment of lung cancer pain was conducted.

Decipher is a tissue-based genomic classifier (GC) developed and validated in the post-radical prostatectomy (RP) setting as a predictor of metastasis. We conducted a prospective randomized controlled cluster-crossover trial assessing the use of Decipher to determine its impact on adjuvant treatment after RP.

Preclinical studies demonstrated that dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways delay the emergence of resistance to EGFR tyrosine kinase inhibitors (TKIs), and in trials with first-generation EGFR TKIs, the combination of EGFR VEGF pathway inhibitors prolonged progression-free survival (PFS).

Imlunestrant is an oral selective estrogen receptor degrader with favorable safety and preliminary efficacy in patients with advanced breast cancer. Pharmacodynamic (PD) biomarker data can optimize drug dosing; in this study, we present PD data from the EMBER-2 study.

A robust prognostic and biological classification for newly diagnosed follicular lymphoma (FL) using molecular profiling remains challenging. FL tumors from patients treated in the RELEVANCE trial with rituximab-chemotherapy (R-chemo) or rituximab-lenalidomide (R2) were analyzed using RNA sequencing, DNA sequencing, immunohistochemistry (IHC), and/or fluorescence in situ hybridization. Unsupervised gene clustering identified 2 gene expression signatures (GSs) enriched in normal memory (MEM) B cells and germinal center (GC) B-cell signals, respectively. These 2 GSs were combined into a 20-gene predictor (FL20) to classify patients into MEM-like (n = 160) or GC-like (n = 164) subtypes, which also displayed different mutational profiles. In the R-chemo arm, patients with MEM-like FL had significantly shorter progression-free survival (PFS) than patients with GC-like FL (hazard ratio [HR], 2.13; P = .0023). In the R2 arm, both subtypes had comparable PFS, demonstrating that R2 has a benefit over R-chemo for patients with MEM-like FL (HR, 0.54; P = .011). The prognostic value of FL20 was validated in an independent FL cohort with R-chemo treatment (GSE119214 [n = 137]). An IHC algorithm (FLcm) that used FOXP1, LMO2, CD22, and MUM1 antibodies was developed with significant prognostic correlation with FL20. These data indicate that FL tumors can be classified into MEM-like and GC-like subtypes that are biologically distinct and clinically different in their risk profile. The FLcm assay can be used in routine clinical practice to identify patients with MEM-like FL who might benefit from therapies other than R-chemo, such as the R2 combination. This trial was registered at www.clinicaltrials.gov as #NCT01476787 and #NCT01650701.

This multicenter, randomized, phase III clinical trial (Northern Radiation Oncology Group of China-002) focused on patients with oligo-organ metastatic non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations. We aimed to investigate whether first-line concurrent thoracic radiotherapy (TRT) and EGFR-tyrosine kinase inhibitors (TKIs), compared with TKIs alone, could achieve better survival.

The treatment of older patients with acute myeloid leukemia (AML) considered unfit for receiving intensive chemotherapy is challenging. Based on the hypothesis that addition of the broad tyrosine kinase inhibitor (TKI) midostaurin could improve the response to hypomethylating agents, irrespective of FLT3 gene mutational status, we conducted a randomized phase II multicenter study to assess the tolerability and efficacy of the addition of midostaurin to a 10-day schedule of decitabine in unfit (i.e. Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) ≥ 3) AML and higher risk myelodysplasia (MDS) patients (HOVON155 trial). In total, 140 eligible patients were randomly (1:1) assigned to treatment with 10-days of decitabine alone (N = 70) or combined with midostaurin (50 mg bid;starting the day following the last dose of decitabine), (N = 70). Addition of midostaurin was well tolerated and the number of AEs was comparable for both treatment arms. Early death rates (< 30 days) were similar as well (10%). In the decitabine plus midostaurin arm 24% reached CR/CRi, the median OS was 4.8 months and 1-yrs OS was 31% which compared with 34% CR/CRi, median OS of 7.4 months and 1-yrs OS of 37% for the decitabine alone group (NS). Thus, while the addition of midostaurin appears safe, it does not enhance therapeutic efficacy of decitabine in unfit AML patients.

Sacituzumab govitecan (SG) significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in hormone receptor-positive human epidermal growth factor receptor 2-negative (HR+HER2-) metastatic breast cancer (mBC) in the global TROPiCS-02 study. TROPiCS-02 enrolled few Asian patients. Here we report results of SG in Asian patients with HR+HER2- mBC from the EVER-132-002 study. Patients were randomized to SG (n = 166) or chemotherapy (n = 165). The primary endpoint was met: PFS was improved with SG versus chemotherapy (hazard ratio of 0.67, 95% confidence interval 0.52-0.87; P = 0.0028; median 4.3 versus 4.2 months). OS also improved with SG versus chemotherapy (hazard ratio of 0.64, 95% confidence interval 0.47-0.88; P = 0.0061; median 21.0 versus 15.3 months). The most common grade ≥3 treatment-emergent adverse events were neutropenia, leukopenia and anemia. SG demonstrated significant and clinically meaningful improvement in PFS and OS versus chemotherapy, with a manageable safety profile consistent with prior studies. SG represents a promising treatment option for Asian patients with HR+HER2- mBC (ClinicalTrials.gov identifier no. NCT04639986 ).

Genetic testing to identify germline high-risk pathogenic variants in breast cancer susceptibility genes is increasingly part of the breast cancer diagnostic pathway. Novel patient-centred pathways may offer opportunity to expand capacity and reduce turnaround time.

Over the past decade, the realm of immunotherapy-based combination therapy has witnessed rapid growth for renal cell carcinoma (RCC), however, success has been constrained thus far. This limitation primarily stems from the absence of biomarkers essential for identifying patients likely to derive benefits from such treatments.

A phytoestrogen-rich diet has been suggested to reduce tumor proliferation among men with prostate cancer, and the effect may differ between men with different polymorphisms of the estrogen receptor-beta gene (ERβ). Patients with low- or intermediate-risk prostate cancer scheduled for radical prostatectomy were randomized to an intervention group (n = 71) provided with soybeans and flaxseeds (∼200 mg phytoestrogens/day) to eat until surgery (approximately 6 wk) or to a control group (n = 69). Tumor proliferation was assessed using Ki-67 indexes, prostate-specific antigen (PSA) concentrations were analyzed in blood, and ERβ polymorphism was genotyped in all subjects. The intervention group had a 13% unit lower risk [95% confidence interval (CI): -28%, 1.8%] of a higher Ki-67 index compared to controls, but the effect was most pronounced among TT carriers of ERβ [risk difference (RD) -19%, 95% CI: -45%, 6.8%]. Subjects with genotype TC/CC had a lower risk (RD -29%, 95% CI: -46%, -1.2%) and TT genotype a higher risk (RD 25%, 95% CI: 8.7%, 42%) of increased PSA concentration, comparing the intervention group to controls. In conclusion, a phytoestrogen-rich diet may cause lower tumor proliferation and concentration of PSA in men with prostate cancer with a specific genetic upset of ERβ.

To compare the performance of cytology, HPV16/18 genotyping and PAX1/SOX1 methylation for the triage of high-risk HPV-positive cervical samples.