Accurate presurgical prediction of pathological complete response (pCR) can guide treatment decisions, potentially avoiding unnecessary surgeries and improving the quality of life for cancer patients. We developed a minimal residual disease (MRD) profiling approach with enhanced sensitivity and specificity for detecting minimal tumor DNA from cell-free DNA (cfDNA). The approach was validated in two independent esophageal squamous cell carcinoma (ESCC) cohorts. In a cohort undergoing neoadjuvant, surgical, and adjuvant therapy (NAT cohort), presurgical MRD status precisely predicted pCR. All MRD-negative cases (10/10) were confirmed as pCR by pathological evaluation on the resected tissues. In contrast, MRD-positive cases included all the 27 non-pCR cases and only one pCR case (10/10 vs 1/28, P < 0.0001, Fisher’s exact test). In a definitive radiotherapy cohort (dRT cohort), post-dRT MRD status was closely correlated with patient prognosis. All MRD-negative patients (25/25) remained progression-free during the follow-up period, while 23 of the 26 MRD-positive patients experienced disease progression (25/25 vs 3/26, P < 0.0001, Fisher’s exact test; progression-free survival, P < 0.0001, log-rank test). The MRD profiling approach effectively predicted the ESCC patients who would achieve pCR with surgery and those likely to remain progression-free without surgery. This suggests that the cancer cells in these MRD-negative patients have been effectively eliminated and they could be suitable candidates for a watch-and-wait strategy, potentially avoiding unnecessary surgery.

This paper mainly analyzes the typical thermodynamic response (thermal history, thermal strain and residual stress) in a conventional continuous-wave (CW) laser during Directed Energy Deposition (DED). The influence of process parameters (laser power and scanning speed) on the temperature gradient in the heat-affected zone, thermal strain and residual stress are studied, and the corresponding relationship are established. The results show that a reduction in residual stress can be obtained by decreasing the temperature gradient. However, the method of reducing the temperature gradient by changing process parameters leads to low forming quality and low density. A pulse-wave laser (PW) is proposed to actively control the residual stress of the deposited sample. This laser mode can reduce not only the temperature gradient in the process of DED but also the in situ release of thermal stress, correspondingly greatly reducing the residual stress.

Despite the lack of predictive biomarkers and a prognostic stratification strategy, immune checkpoint inhibitor (ICI) has shown promise in improving outcomes for patients with limited-stage small cell lung cancer (LS-SCLC). We evaluated the potential of circulating tumor DNA (ctDNA) to dynamically predict outcomes in patients with LS-SCLC receiving concurrent chemoradiotherapy (CCRT) with or without consolidation ICI. We analyzed 490 serial samples collected from 144 LS-SCLC patients at baseline (t0), post-induction chemotherapy and pre-thoracic radiotherapy (t1), post-radiotherapy (t2), and progressive disease (t3). For 44 patients receiving consolidation ICI with serplulimab, an investigational PD-1 inhibitor, ctDNA dynamics during consolidation ICI were also assessed at multiple time points. Patients with undetectable ctDNA after CCRT had good outcomes with or without consolidation ICI, whereas ctDNA-positive patients at t2, indicating poor response to CCRT, derived survival benefit from consolidation ICI. Notably, ctDNA status at t1 appeared more predictive than at t2. A three-level risk stratification strategy integrating t1 ctDNA status with radiological tumor shrinkage identified a high-risk subgroup of patients who achieved significantly improved progression-free survival (PFS) (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.08–0.75; p = 0.014) and overall survival (OS) (HR, 0.06; 95% CI, 0.00–0.42; p = 0.001) from consolidation ICI, prioritizing CCRT plus consolidation ICI. Furthermore, maintaining ctDNA negativity during consolidation ICI was associated with favorable outcomes. These data provide valuable insights into the individualized management of LS-SCLC in the era of immunotherapy.