MSI-H/dMMR

P2, N=40, Recruiting, VA Office of Research and Development | N=30 --> 40 | Trial primary completion date: Mar 2025 --> Dec 2025

In pMMR/MSS mCRC, gLOH-high was associated with worse prognosis and higher benefit from the addition of anti-PD-L1 agents to chemotherapy. If confirmed in larger series, these results may inform the design of clinical trials.

The current evidence and clinical experience suggest that patients with advanced MSI-H are likely to benefit from immunotherapy and should be considered for early systemic treatment with immunotherapy as a central component. At present, research studies on the molecular characteristics of SMEGC are limited, underscoring the importance of conducting comprehensive molecular diagnostics of each EGC patient, which could help clinicians thoroughly understand the lesion's characteristics.

This case illustrates the importance of performing HTS in rare sarcomas given the availability of efficient therapies, such as those for tumors displaying high TMB or MMRd/MSI. In agreement with other reports, it supports the contention that MMRd/MSI status and high numbers of TILs are valuable predictive markers of response to immunotherapy in sarcomas.

ctDNA-MSI kinetics divided into three groups (increase, decrease and negative) correlated strongly with PFS (PFS at 24 months was 0%, 53.0% and 77.0%, respectively; p<0.001) and remained significant in multivariate analysis (HR=7.93; 95% CI, 2.23-28.21; p=0.005). Since there is no strong predictor of ICI efficacy in dMMR and/or MSI CRC patients, these results suggest that ctDNA-MSI could help physicians in treatment decision-making in the future.

A post hoc analysis displayed higher frequency of M-MDSCs (p = 0.020) and lower frequency of CD4+ (p < 0.005) at pretreatment in EC patients as compared to healthy donors. In conclusion, the peripheral evaluation of MDSCs and Tregs correlated with molecular features in EC treated with CP/CPA and may add insights in identifying EC patients responder to first-line chemo/chemo-immunotherapy.

We describe baseline methodological predictors of non-response to immunotherapy and propose a strategy for selecting potential non-responders. These findings warrant further investigation.

Upfront NGS offers rapid, comprehensive genomic data, guiding tailored therapies and trials in advanced NSCLC. Liquid rebiopsy at progression further refines treatment decisions.

We present the first long-term projections for cancer prevalence associated with key pan-tumour biomarkers in Australia, to inform health policy and healthcare planning for targeted therapies. Medical Research Future Fund-Preventive and Public Health Research Initiative-2019 Targeted Health System and Community Organization Research Grant Opportunity (MRF1200535), Cancer Institute NSW Career Development Fellowship (2022/CDF1154), National Health and Medical Research Council of Australia Investigator Grant (APP1194679).

The patient initially received nab-paclitaxel plus gemcitabine, achieving tumor shrinkage. Upon tumor regrowth, she was treated with the anti-programmed cell death-1 immune checkpoint inhibitor (ICI) pembrolizumab, which resulted in significant tumor reduction. This is the first case report of MCP with dMMR/MSI-H due to MLH1 promoter hypermethylation, effectively treated with an ICI.

The microbiome profoundly affects MSI-driven tumorigenesis. Modulation of the gut microbiota through interventions such as fecal microbiota transplantation, probiotics, and dietary changes holds promise for improving ICI response rates. Further research into cancer pharmacomicrobiomics, investigating the interplay between microbial metabolites and anticancer therapies, is crucial for developing personalized treatment strategies.

Among patients with stage IIIC endometrial cancer, POLE mutated tumors exhibited an extremely low prevalence, with no specific molecular profile emerging as the largest molecular subgroup. Despite the significant difference in recurrence-free survival between molecular classes, conventional histopathologic parameters retained crucial prognostic value. Our findings highlight the necessity of integrating molecular classes with pathological characteristics, rather than considering them in isolation as crucial prognostic factors in stage IIIC endometrial cancer.

First-line durvalumab plus chemotherapy with olaparib, and dostarlimab plus chemotherapy, were more beneficial for survival in the pMMR/MSS and dMMR/MSI-H populations, respectively. Only pembrolizumab plus chemotherapy versus chemotherapy was cost-effective for patients with dMMR/MSI-H endometrial cancer in the USA.

Our study reveals significant differences in SLN involvement among patients with early-stage endometrial cancer based on molecular subtypes. This underscores the importance of considering molecular characteristics for accurate staging and optimal management decisions.

Our data suggest that molecular classification does not seem useful to tailor the need of nodal dissection in apparent early-stage endometrial cancer. p53 abnormality predicts the risk of having advanced disease at presentation. Further external validation is needed.

Tumoral gene expression controlling the PD1 immune checkpoint, particularly expressed in "hot tumors", predicted recurrence-free, disease-specific, and overall survival in patients with endometrial carcinoma in two independent cohorts. Evaluation of these genes could be used to stratify patients who qualify for immune checkpoint inhibitors, which warrants prospective clinical trials.

Endometrial cancer featured different patterns of recurrence depending on the molecular profile. p53-abnormal molecular profiling was the only independent risk factor for peritoneal relapse, while non-specific molecular profile showed a strong association with distant failures.

The integration of molecular and pathologic data may improve risk stratification of pre-menopausal patients with endometrial cancer and enhance candidate selection for ovarian preservation.

The distribution of the molecular subclasses in stage IV endometrial cancer patients differed substantially from the distribution in stage I-III endometrial cancer patients, with the unfavorable subclasses being more frequently present. Although the molecular classification was not prognostic in stage IV endometrial cancer, it could guide adjuvant treatment decisions.

In addition, artificial intelligence has the potential to improve the trial matching process. An integrated approach, combining these innovations in collaboration with multiple stakeholders, is crucial for advancing rare cancer research, offering hope for better patient outcomes and quality of life.

© 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Finally, palbociclib, an inhibitor of CDK4/6, effectively inhibited the proliferation (p < 0.05) and induced apoptosis of oxaliplatin-resistant gastric cancer cells (p < 0.01) in vitro. These findings support the potential value of AURKA and CDK6 amplification, as well as their effects on the tumor microenvironment, in predicting poor outcomes of NACT in patients with locally advanced gastric cancer. Thus, CDK4/6 inhibitors could be used to treat NACT-resistant patients with gastric cancer.

Monitoring these circulating peripheral blood markers in wider population of patients receiving ICI therapy, during its course, may provide a perspective in the development of new biomarkers for predicting response and may serve as a basis for personalized treatment. This case report describes valuable insights into evolution of immune markers predicting and monitoring response to Nivolumab in a patient with cancer.

Our results demonstrate the significant clinical utility of comprehensive genomic profiling in the routine clinical testing of patients with solid tumors.

Notably, 11 samples demonstrated a co-occurrence of MSI and Eh-lectin, with increased expression of miRNA-643 relative to XIAP. The presence of MSI in conjunction with Eh-lectin positivity and elevated miRNA-643 expression, along with reduced levels of the XIAP inhibitor gene in colorectal adenocarcinoma biopsy samples, strongly indicates that this protozoan parasite may play a role in the development of MSI by affecting apoptosis.

Continuous improvement was observed, and conversion surgery involving liver resection, partial inferior vena cava resection, and perihilar and para-aortic lymph nodes dissection was performed with curative intent. No malignant cells were found in any of the resected specimens, consistent with pathological complete response.

ER status improves prognostic stratification within the NSMP subgroup in ENOC, with ER-negative tumors associated with a worse prognosis. These findings may lead to more personalized treatment strategies for ENOC.

Baseline and on-treatment ctDNA dynamics may provide an early indication of benefit from letrozole/abemaciclib in EC. ctDNA at the time of progression may identify resistance alterations that may inform subsequent therapy.

Results also indicated that high microsatellite instability directly correlated with high CNs for most of the above indicated genes. These approaches to assessing tumor metabolism-related genes may lead to more accurate measures of patient risk and potential additional treatment options.

Immune checkpoint inhibitors (ICIs) plus fluorouracil-based chemotherapy (Chemo) have been approved as an initial treatment strategy for metastatic or recurrent human epidermal growth factor receptor 2 (HER2)-negative gastric cancer (GC) or gastroesophageal junction cancer (GEJC)...Therefore, urging the need for more investigations into the development of collaborative prognostic forecasting models for achieving precise stratification, established harmonized testing standards and methods for PD-L1 expression and positivity, optimal CPS threshold for benefits, as well as alternative molecular biomarkers for the reason that certain indicators alone may not discriminate responders clearly. Lastly, dual anti-therapy might be a useful tactic for the population with low PD-L1 expression in the future.

Two of these WRN inhibitors, HRO761 and VVD-133214, have recently entered clinical trials. In this review, we summarize recent studies on WRN as a synthetic lethal target in MSI CRC and the development of WRN inhibitors as a new class of anticancer agents.

Our prognostic risk model could effectively predict the prognosis and response to chemo-immune therapy in patients with GCPM. The risk score is a promising independent prognostic factor that is closely correlated with the immune microenvironment and clinicopathological characteristics.

PD-(L)1 inhibition demonstrated significant efficacy in patients with advanced or recurrent MMRd endometrial cancer. In NSMP endometrial cancer, adding a PD-(L)1 inhibitor to platinum-based chemotherapy showed potential benefit, whereas in p53abn endometrial cancer, such benefit was not found. POLEmut endometrial cancer, although rare in recurrent or metastatic settings, was associated with a favorable prognosis, regardless of treatment. These findings underscore the relevance of the molecular classification of endometrial cancer and highlight the importance of prioritizing molecular analyses in clinical trials to guide personalized PD-(L)1 inhibition strategies.

© RSNA, 2025 Supplemental material is available for this article. See also the editorial by Lev-Cohain and Sosna in this issue

The only curative therapy for AACC with involvement of the duodenum is en bloc RHPD. Here, we described a case in which long-term survival was achieved by ensuring R0 with en bloc resection.

P2, N=15, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

P1/2, N=25, Active, not recruiting, Radboud University Medical Center | Trial completion date: Dec 2024 --> Sep 2025

SCC of the vulva and vagina is expected to have high TMB, and gene alteration status differed between TMB-high and non-TMB-high groups.

P1/2, N=348, Completed, Hutchmed | Recruiting --> Completed | Trial completion date: Dec 2025 --> Dec 2024

Prognosis correlated with high-risk morphologic features in the adenosarcomatous component, including sarcomatous overgrowth, extensive rhabdomyosarcomatous differentiation, vascular invasion, and high-grade nuclear atypia. "Mixed endometrioid adenocarcinoma and adenosarcoma" is a clonal biphasic malignant neoplasm of uncertain histogenesis, with a high frequency of DICER1 mutations.

Two of these had confirmed dMMR tumor status: one demonstrated a sustained complete response on pembrolizumab monotherapy for 44 months; the other had a partial response on ipilimumab and nivolumab for 31 months but died from an unrelated cause. While rare, sarcoma can be encountered in patients with LS, particularly those with germline MSH2 mutation. LS-associated sarcomas occur significantly earlier, carry a favorable outcome, and demonstrate the potential for durable response with immunotherapy.

Oncological outcomes differ by molecular groups, in particular among patients with advanced disease. Patients with p53 abnormal tumors have the worst outcome, while patients with POLE mutated tumors have favorable outcomes even with recurrent disease. Implementation of the addition of immunotherapy to chemotherapy is expected to lead to substantial improvement of outcome, particularly in patients with mismatch repair deficient advanced/recurrent disease. There is still a high unmet need in advanced/recurrent patients with p53 abnormal and no specific molecular profile tumors.