The nonavalent human papillomavirus (9vHPV) vaccine protects against HPV infection and high-grade squamous intraepithelial lesions (HSIL) when administered prior to exposure, but evidence supporting its potential therapeutic benefit has been inconsistent. This randomized, double-blind, placebo-controlled trial evaluated whether the 9vHPV vaccine reduces recurrence of HSIL or HPV persistence in 27-69-year-old persons previously treated for anal or vulvar HSIL. Participants were HSIL-free at enrollment and received 9vHPV or placebo at months 0, 2, and 6. High-resolution anoscopy or vulvoscopy was performed at months 18 and 36, and anal or vulvar swabs were collected at months 0, 18, 24, and 36 for HPV DNA detection. The primary endpoints were HSIL recurrence and HPV persistence (≥2 consecutive positive swabs for the same 9vHPV-type). Of 185 participants included in the intent-to-treat analysis, 91 received vaccine and 94 received placebo. The DSMB recommended early termination for futility. The 9vHPV vaccine was not more effective than placebo in preventing recurrent HSIL, with 16 HSIL among 9vHPV recipients versus 21 HSIL in placebo recipients (incidence 8.1 vs. 10.1/100 person-years; p = .54). HPV persistence was 21% in vaccine versus 31% in placebo recipients (p = .20). The 9vHPV vaccine delivered after treatment of anal or vulvar HSIL did not reduce HSIL recurrence or HPV detection. Our study underlines the importance of HPV vaccine administration prior to HPV exposure and the need for novel treatments for HSIL with high recurrence potential.

A recent first-in-human clinical trial demonstrated that survival in glioblastoma (GBM) patients following rQNestin34.5v.2 oncolytic virus treatment was associated with immune activation signatures. This study was registered at ClinicalTrials.gov (NCT03152318). Here, we provide in situ evidence of ongoing T cell-mediated cytotoxicity against tumor cells at late time points following single treatment, with deep and persistent T cell infiltration into tumor regions. Shorter distances between cleaved caspase-3+ tumor cells and granzyme B+ T cells were associated with longer progression-free survival following treatment. Pre-existing tumor-infiltrating T cells expanded locally upon treatment, correlating with longer overall patient survival. T cells with an early activation program closely interacted with tumor cells and were strongly enriched upon treatment. Viral remnants were restricted to necrotic regions, while T cells infiltrated deeply into live tumor regions. These data demonstrate that single oncolytic virus treatment can expand pre-existing T cell clones and trigger persistent T cell-mediated immunity against GBM.

Identifying patients who are most likely to benefit from the combination of bevacizumab and chemotherapy (Bev/CT) is essential for the optimal management of metastatic colorectal cancer (mCRC). The aim of this study is to investigate the utility of chronic inflammatory biomarkers in predicting clinical response to Bev/CT and outcomes in patients with mCRC.

Dual anti-CTLA-4/PD-1 inhibitors show efficacy in numerous malignancies. We are the first to report on the efficacy of ipilimumab-nivolumab immunotherapy in a dedicated cohort of patients with gynecologic clear cell carcinomas (CCCs), which are rare, aggressive cancers.

ASP9801, an oncolytic virus encoding interleukin-7 and interleukin-12, was assessed for safety, tolerability, pharmacokinetics, and antitumor activity in patients with advanced solid tumors in a Phase 1 study.

Neoadjuvant endocrine therapy (NET) is used in hormone receptor (HR)-positive, HER2-negative breast cancer to reduce tumor burden before surgery. However, robust biomarkers to predict benefit from NET are lacking.

Etoposide plus cisplatin (EP) with concurrent accelerated hyperfractionated thoracic radiotherapy (AHTRT) remains the standard treatment for unresectable limited-stage (LS) small cell lung cancer (SCLC)) for over two decades. Our previous study demonstrated that amrubicin plus cisplatin (AP) with once-daily thoracic radiotherapy (50 Gy per 25 fractions) for LS-SCLC prolonged overall survival (OS) to 39.5 months with manageable toxicities. To enhance therapeutic efficacy, this study aimed to assess the feasibility of AP combined with AHTRT for LS-SCLC.

Epidermal growth factor receptor (EGFR) exon 20 insertions (Ex20ins) are the third most common type of EGFR mutation, occurring in up to 12% of EGFR-mutated non-small cell lung cancers (NSCLC). Ex20ins-mutated NSCLC can be resistant to most approved tyrosine kinase inhibitors (TKIs). The Phase III PAPILLON trial (NCT04538664) demonstrated that amivantamab plus chemotherapy significantly improves progression-free survival (PFS) compared to chemotherapy alone, leading to its approval as a first-line treatment for patients with Ex20ins NSCLC. PAPILLON further evaluated patient-reported outcomes (PROs) and time to symptomatic progression (TTSP).

Amivantamab is a bispecific, epidermal growth factor receptor (EGFR) and MET-proto-oncogene (MET)-targeting antibody with immune cell-directing activity. In the global Phase 3 PAPILLON trial, amivantamab plus carboplatin-pemetrexed (amivantamab-chemotherapy) significantly improved progression-free survival (PFS) vs chemotherapy alone in previously untreated participants with locally advanced/metastatic NSCLC with EGFR exon 20 insertions (Ex20ins). We evaluated clinical outcomes in Asian participants in PAPILLON (NCT04538664).

Anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 (ROS1) rearranged non-small cell lung cancers (NSCLC) develop bypass resistance mechanisms that activate mitogen-activated protein kinase (MAPK) pathway signaling. We conducted a study to evaluate the ALK/ROS1 inhibitor lorlatinib combined with MAPK pathway inhibitors: binimetinib (MEK inhibitor) or TNO155 (SHP2 inhibitor).

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a unique myeloid malignancy with CD123 interleukin-3 receptor-α overexpression and poor prognosis.

This study used contemporaneous networks and cross-lagged panel network (CLPN) to examine how the Simplified Sitting Badunjin (SSBDJ) intervention interacted with the fatigue, sleep disturbances, and quality of life (QoL) at different follow-up stages in advanced cancer patients.

To test the effectiveness of a surgical web-based decision aid (DA) in improving knowledge.

Mitoxantrone hydrochloride injection for tracing (MHI) is a novel lymphatic tracer recommended for sentinel lymph node (SLN) biopsy (SLNB) in breast cancer. However, whether MHI can be detected under near-infrared fluorescence and the optimal MHI concentration and injection timing for SLNB remain unclear. This study characterized the fluorescent properties of MHI and explored its optimal application conditions for SLNB.

In nasopharyngeal carcinoma, cisplatin is known to be associated with poor treatment compliance and notable side effects. More effective and safer platinum drugs are needed for the treatment of patients with nasopharyngeal carcinoma. In 2021, our multicenter, randomized, phase 3 trial reported that lobaplatin and fluorouracil induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than did cisplatin-based therapy in nasopharyngeal carcinoma. Data from the 10-year survival analysis are updated here. With a median follow-up of 10.6 years in the intention-to-treat population, 10-year progression-free survival is 70.7% in the lobaplatin-based therapy group vs. 71.9% in the cisplatin-based therapy group (HR 1.02, 95% CI 0.72-1.43; log-rank p = 0.885). The difference between the groups is 1.2% (95% CI -6.7-9.1, pnon-inferiority = 0.015), which is lower than the prespecified non-inferiority margin of 10%. The results are similar when we analyze patients in the per-protocol population. In the univariable and multivariable analyses, stage is an independent prognostic factor for progression-free survival (p = 0.001). The subgroup analyses suggest that the non-inferiority of lobaplatin-based therapy did not differ among specific populations. The incidence of late toxic effects is similar between the therapy groups, except for grades 1-2 peripheral neuropathy (p = 0.033), grades 1-2 deafness/otitis (p = 0.021), and grades 1-2/3 nephrotoxicity (p = 0.005; p = 0.021), the incidence of which is greater in the cisplatin-based therapy group than in the lobaplatin-based therapy group. Our findings suggest that lobaplatin and fluorouracil induction chemotherapy plus lobaplatin-based concurrent chemoradiotherapy is an alternative doublet treatment strategy to cisplatin-based concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma.

To assess treatment with camrelizumab (a programmed death 1 inhibitor) in addition to concurrent chemoradiotherapy and as a maintenance treatment in patients with high risk nasopharyngeal carcinoma.

Biliary tract cancer (BTC) is an aggressive malignancy with limited treatment options and a poor prognosis. Although immune checkpoint inhibitors combined with chemotherapy have improved patient outcomes, their toxicity remains concerning. This phase II multicenter trial evaluated the efficacy and safety of pembrolizumab plus lenvatinib with a reduced-dose gemcitabine and oxaliplatin (GEMOX) regimen as a first-line therapy for advanced BTC.

Biospecimen analyses may provide important insights into patient selection and pharmacodynamic effects. To provide generalizable findings, such studies must enroll adequate and diverse populations.

The EXTREME regimen is the standard first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC), but it is poorly tolerated in Asian patients. We aimed to compare the efficacy and safety of the modified EXTREME (mEXTREME) and modified TPEx (mTPEx) regimens in Japanese patients.

The optimal neoadjuvant strategy for high-risk locally advanced rectal cancer (LARC) remains a matter of debate. This study evaluated the efficacy and safety of neoadjuvant FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, irinotecan) plus bevacizumab without radiotherapy in patients with magnetic resonance imaging-defined high-risk LARC.