POLD1 mutation

P1, N=115, Recruiting, Jecho Biopharmaceuticals Co., Ltd.

Question Assessment of pathological complete response after neoadjuvant immunotherapy for locally advanced colorectal cancer is crucial, but it cannot be identified by the current radiological criteria. Findings Morphological changes exhibit predictive value for pathological complete response, and the combined model integrating morphological changes and endoscopy further shows promising potential. Clinical relevance Radiographic complete response alone is insufficient for accurately predicting pathological complete response (pCR). Pseudoresidual disease is common in pCR. Dissociated response may guide personalized treatment. Recognizing imaging features of immune-related adverse events is critical to avoid misdiagnosis as metastatic disease.

P2, N=35, Recruiting, Sun Yat-sen University | Trial completion date: Jan 2024 --> Dec 2029 | Trial primary completion date: Jan 2024 --> Jan 2028

P2, N=21, Active, not recruiting, Rutgers, The State University of New Jersey | Recruiting --> Active, not recruiting | N=40 --> 21 | Trial completion date: Oct 2023 --> Sep 2027

These molecular tools have the potential to change how CRC is managed by earlier detection and more precise predictive biomarkers. However, large-scale validation and clinical standardization are still crucial for their extensive utilization.

Integrating multiple biomarkers may provide superior stratification and guide therapeutic strategies. Prospective validation and standardized biomarker assessment will be imperative to translate these insights into clinical practice.

P2, N=197, Recruiting, Gruppo Oncologico del Nord-Ovest | N=140 --> 197

Benign struma ovarii do not harbor BRAF alterations. DICER1 and POLD1 variants need further investigation in this tumor pathology.

Postoperatively, the patient received 4 cycles of XELOX chemotherapy plus nivolumab, followed by consolidative radiotherapy synchronized with capecitabine and nivolumab, and subsequent maintenance therapy with capecitabine and nivolumab until sustained no evidence of disease (NED) was confirmed in January 2023. This exceptional and sustained response may be attributed to the synergistic effect of TMB-H and POLD1 mutation, which enhance neoantigen generation and sensitize tumors to immunotherapy. This case highlights the potential of biomarker-driven chemo-immunotherapy combined with MDT-guided multimodal treatment (surgery + adjuvant therapy + consolidative radiotherapy) to achieve curative intent in patients with metastatic GMC, providing valuable insights for personalized treatment strategies in this poor-prognosis population.

MMR and p53 IHC serve as practical frontline tools, while POLE sequencing should be prioritized for intermediate- and high-risk endometrioid tumors. Expanded molecular testing in Asian populations is essential to refine risk stratification and optimize individualized management.

The most frequently mutated gene is NOTCH1. Extensive fusion gene, expression and molecular cluster analyses provide a molecular portrait of this rare and enigmatic tumour type.

It also includes a concise summary of functional significance for each variant. PolED aims to assist in clinical decision-making, guide personalized therapy, and promote further research.