The 2025 ASCO Annual Meeting, the world's most authoritative academic event in oncology, will take place in Chicago from May 30 to June 3. This premier global conference showcases the year's most cutting-edge clinical research and therapeutic advancements in cancer care. Genecast was selected for presentation with three collaborative studies with clinical experts, selected for presentation at this year's meeting. Below, we highlight these groundbreaking research advancements:

01. Prognostic value of postoperative circulating tumor DNA and tumor markers in resected pancreatic adenocarcinoma (PAAD): an interim analysis of a prospective observational study

Poster Bd # 482

Background: Despite the benefits of postoperative adjuvant chemotherapy, recurrence rates of PAAD remain as high as 60% within the first year, underscoring the need for improved strategies to optimize treatment plans. This prospective observational study aims to evaluate the potential of postoperative ctDNA-based minimal residual disease (MRD) as an early predictor of disease relapse in resected PAAD using next-generation sequencing.

Methods: Pathologically confirmed stage I-III PAAD patients who underwent surgical resection and carried KRAS mutations were enrolled. Eligible criteria included negative surgical margins and no metastasis prior to adjuvant therapy. Patients who did not receive adjuvant therapy were excluded. Tumor tissue samples collected during surgery were analyzed using a 769-gene NGS panel, while plasma samples were obtained at landmark (4–8 weeks post-operation and pre-therapy), 12-, 24-, 36-, and 48-weeks post-operation, and 2 weeks post-adjuvant therapy. Plasma samples were assessed for MRD using MinerVa (Genecast Biotechnology). Concurrently, tumor biomarkers such as CA19-9 were measured. The primary endpoint was overall survival (OS), while the secondary endpoint was disease-free survival (DFS). The trial is designed for a total follow-up period of three years.

Results: As of November 27, 2024, a total of 133 patients underwent MRD analysis. KRAS mutations were distributed as follows: p.G12D in 55%, p.G12V in 27%, p.G12R in 13% and other subtypes in 5%. Nine patients were excluded due to loss of follow-up, and 12 were excluded for less than six months of follow-up, leaving 112 patients for this interim analysis. MRD positivity rates were 16%, 9%, 10%, 15%, 11%, and 11% at landmark, 12, 24, 36, 48 weeks, and 2 weeks post-therapy, respectively. Landmark MRD positivity was a significant predictor of disease recurrence (HR = 2.39, 95%CI:1.14-5.01, p = 0.017). Combining landmark MRD with biomarker CA19-9 improved prognostic accuracy (HR = 2.70, 95%CI:1.4-5.5, p = 0.002). Patients with longitudinal MRD-positive (detected at any time point excluding landmark or relapse) had significant worse DFS (HR = 3.13, p = 0.001) and worse OS (HR = 0.73, p = 0.001) compared to those with negative MRD. Analysis of MRD status at landmark and week 36 revealed that patients transitioning from MRD-positive to MRD-negative (clearance) had significantly better DFS compared to those with persistent MRD positivity (p = 0.023). Notably, no patients deceased from the MRD clearance group.

Conclusions: These findings underscore the clinical utility of integrating landmark and longitudinal MRD assessments with tumor markers for comprehensive risk stratification and prognostication in resected PAAD patients. This approach could potentially guide personalized treatment strategies and improve patient outcomes.

02. Prospective validation of dynamic circulating tumor DNA (ctDNA)-based MRD for predicting progression-free survival and treatment benefit in oral cancer

Abstract # e18090

Background: Effective disease control in oral cancer heavily relies on the accurate identification and management of minimal residual disease (MRD). This study investigated the association of ctDNA-based MRD with progression-free survival (PFS), and its potential to predict treatment benefits.

Patients and Methods: A prospective cohort study was conducted at Shanghai Ninth People’s Hospital, a tertiary care center involving patients with biopsy-proven squamous cell carcinoma of oral cavity reported between January 2021 and December 2023. Tumor tissues and plasma samples were collected, processed, and sequenced for ctDNA analysis using a 769-gene panel. A tumor-informed strategy, MinerVa (Genecast Biotechnology), was utilized for variants tracking and MRD assessment. ctDNA status was recorded at various time points, including pre-operative, post-operative, and follow-up visits. The primary endpoint of the study was progression-free survival (PFS).

Results: As of November 2024, 46 patients were included in the analysis, with a median follow-up period of 297 days. All patients were HPV negative. Eleven (24%) patients experienced disease recurrence, of whom, 3 patients died. Out of 44 patients with post-operative MRD analyzed, 10 (23%) patients were MRD positive. MRD positivity significantly predicted poorer PFS, with a hazard ratio (HR) of 6.07 (95%CI=1.60-22.8, p=0.002) and a negative predictive value (NPV) of 85%. Both MRD and pathological N-stage (pN-stage) were significant predictors of PFS (p=0.002, and p=0.011, respectively). In multivariate analysis, MRD positivity remained an independent predictor of PFS (HR=8.50, p=0.024) even when adjusted for tumor size, pN-stage, and adjuvant treatment regimen. Notably, among post-operative MRD-positive patients, those receiving adjuvant therapy demonstrated significantly better PFS compared to those who did not (HR=5.68, p=0.035). Conversely, adjuvant therapy showed no significant effect in MRD-negative patients (p=0.656). Furthermore, longitudinal analysis of ctDNA in plasma samples collected after surgery but before relapse revealed a positivity rate of 28% (13/46), with the NPV increasing up to 91%.

Conclusions: Post-operative ctDNA-based MRD shows promise for identifying disease recurrences and stratifying patients likely to benefit from adjuvant treatment. Continuous MRD assessment during and after adjuvant therapy plays a critical role in disease monitoring and potentially improving clinical outcomes for oral cancers patients.

03. Efficacy and molecular predictors of radiotherapy combined with bevacizumab on desmoid tumor (aggressive fibromatosis)

Abstract # e23535

Background: Desmoid tumors are rare, highly recurrent soft-tissue tumors with limited responses to non-surgical therapies. Radiotherapy combined with bevacizumab, a VEGF inhibitor, has shown potential synergy in improving tumor response. This study evaluated the efficacy and safety of radiotherapy combined with bevacizumab and explored potential molecular predictors of response.

Methods: From a cohort of 160 patients with desmoid tumors treated at Sichuan Cancer Hospital between June 2013 and September 2023, eight patients who underwent radiotherapy combined with bevacizumab were retrospectively analyzed. Clinical outcomes, including tumor response according to RECIST 1.1 and time to treatment failure (TTF), were assessed alongside health-related quality of life (QoL) using the EORTC QLQ-C30 questionnaire. Tumor specimens were analyzed for β-catenin and VEGF expression, microvessel density (MVD) via immunohistochemistry, and genetic mutations, including CTNNB1, using next-generation sequencing (NGS).

Results: The study included eight patients (ages 18–69, median 30) with equal male-to-female distribution and tumors located in the chest wall, head and neck, or intrathoracic regions. Patients received radiotherapy (median dose: 51 Gy, range: 45–65.5 Gy) with concurrent or sequential bevacizumab (2–5 cycles, 200–345 mg per cycle). All exhibited nuclear β-catenin positivity, with seven harboring CTNNB1 mutations. VEGF expression was present in five patients, and MVD ranged from 7 to 29 (median: 15). Clinical responses included complete response (CR) in three patients (37.5%) and partial response (PR) in four (50%), and all patients remained progression-free with a mean TTF of 53.25 months (range: 10–134 months). Favorable QoL scores (mean: 90.6 ± 12.1) were observed. No correlation was observed between clinical response and CTNNB1 mutations, VEGF expression, or MVD. However, ATR gene alterations, involved in DNA repair, were exclusively identified in patients with CR. Functional enrichment analysis indicated that mutations were predominantly associated with pathways regulating DNA repair, angiogenesis, and endothelial cell differentiation.

Conclusions: Radiotherapy combined with bevacizumab demonstrated significant efficacy and safety in desmoid tumors, with sustained tumor control and good QoL. ATR gene alterations may serve as potential predictors of response, warranting further prospective studies to elucidate their role.