Oncology — Weekly Evidence Brief

Ultrasensitive circulating tumor DNA (ctDNA) detection below 80 parts per million, both pre- and postoperatively, is highly prognostic in non-small cell lung cancer (NSCLC), improving disease stratification and informing adjuvant therapy decisions by identifying patients who "clear" ctDNA and experience improved outcomes 1. Liquid biopsy, including ctDNA, also serves as a minimally invasive tool to rapidly detect resistance mechanisms to targeted therapies in NSCLC, complementing or replacing tissue re-biopsy and dynamically profiling tumors 2. While guideline-concordant biomarker testing for common alterations like EGFR and ALK is high in NSCLC, testing rates for rarer biomarkers with newly approved therapies still lag, highlighting a need for faster adoption of novel biomarker testing 3.

Immunotherapy, either as first-line or subsequent-line treatment, significantly prolongs overall survival in extensive-stage small-cell lung cancer (ES-SCLC), with local thoracic radiotherapy maintaining its significant survival benefit in this setting 4. For advanced EGFR-mutant NSCLC, concurrent thoracic radiotherapy (TRT) with first-line EGFR-tyrosine kinase inhibitors (TKIs) remarkably extends median progression-free survival across various TKI generations and patient subgroups, including those with brain metastases, while also reducing primary and distant progression risks with favorable safety 5.

In HER2-positive breast cancer, dynamic immunophenotyping using spatial expression profiling can predict pathologic complete response (pCR) to neoadjuvant chemotherapy combined with trastuzumab, offering a basis for subsequent treatment selection 6. For early-stage hormone receptor-positive (HR+), HER2-negative breast cancer, the addition of CDK4/6 inhibitors to endocrine therapy improves invasive disease-free survival, with a strong trend toward improved distant recurrence-free survival, although overall survival benefits require longer follow-up 78. Adjuvant chemotherapy for locoregional recurrence of HR-positive HER2-negative breast cancer is associated with better invasive disease-free survival, particularly for non-ipsilateral breast tumor recurrence and recurrences during adjuvant endocrine therapy without prior perioperative chemotherapy 9.

Whole genome sequencing (WGS) in metastatic colorectal cancer (mCRC) identifies significantly more clinically actionable biomarkers than standard diagnostics, increasing the proportion of patients eligible for personalized therapeutic interventions 1011. Automated circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) counts demonstrate a strong association with survival in mCRC, with simulations suggesting that optimizing treatment timing for high-risk patients based on these biomarkers could significantly improve median survival outcomes while also reducing costs and environmental burden compared to routine imaging 12. Single-cell RNA sequencing further reveals distinct prognostic markers and tumor microenvironment features underlying chemotherapy progression in colorectal cancer, including specific immune cell signatures and chemo-protective markers, which can provide insights into resistance mechanisms and guide future strategies for improved patient outcomes 1314.

Advanced methodologies like TMBclaw, a tumor clone-aware graph learning framework, improve immunotherapy response prediction by accounting for intratumoral clonal heterogeneity and enabling cross-cohort knowledge transfer 15. Additionally, multicellular immune ecotypes within solid tumors show promise as prognostic and predictive biomarkers for real-world therapeutic benefits from immune checkpoint inhibitors (ICIs) across various cancer types 16. While ICI monotherapy may have limited efficacy in challenging cancers like pancreatic ductal adenocarcinoma (PDAC), combination therapy with ICIs and a CD40 agonistic antibody has shown to significantly extend survival and reduce tumor burden in preclinical models 17. Although subsequent ICI therapies after initial failure can show responses in some cancers, particularly melanoma, the overall evidence supporting their efficacy across various tumor types remains low, highlighting a need for further research 18.