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Background: The matter of postoperative radiotherapy (PORT) in esophageal cancer (ESCA) was far from conclusive. Some evidence indicated that lymph node status could affect treatment. We evaluated lymph node ratio (LNR) as an indicator that could be applied to predict PORT benefit., Methods: Retrospective cohort study collected the data of N1, N2, N3 stage ESCA patients from the Surveillance, Epidemiology, and End Results database (SEER) to analyze the association between LNR and prognosis from 2004 to 2015. Patients were categorized into two subsets based on the LNR cut-off value of 0.23 using receiver operating characteristic curve (ROC). Kaplan-Meier analysis was utilized to estimate the proportion of overall survival (OS) and esophagus cancer-specific survival (CSS) in two LNR groups. Cox regression analysis and competitive risk model was adopted to investigate the impacts of LNR on prognosis., Results: Of 2,165 ESCA patients identified, 1,165 (53.8%) had LNR>0.23. The LNR was an independent prognostic factor and associated with better OS and CSS of LNR≤0.23 (P < 0.001). In competitive risk model, a worse CSS was analyzed of LNR>0.23 (HR = 1.71; 95% CI 1.53-1.91). Subgroup analyses indicated that PORT was associated with favorable OS and CSS. Furthermore, when stratified by Node stage, PORT was associated with a survival benefit only in N1 stage with higher LNR (LNR>0.23) after adjusting for other covariates., Conclusions: LNR exceeding 0.23 was negatively associated with prognosis in ESCA. The survival benefit from PORT in ESCA seems to be limited to LNR of 23% or more only in N1 stage. This study highlights the biomarker meaning of LNR on identifying PORT beneficiary in N1 stage., Competing Interests: Declaration of competing interest All authors have completed the ICMJE uniform disclosure form. The authors have no conflicts of interest to declare., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: Genome-wide chromosomal instability, instead of specific somatic mutations or copy-number alterations in selected genes, is a significant property of cancer and may suggest a new strategy for treatment. Here we utilized cell-free DNA (cfDNA) sequencing to display the whole picture of chromosomal instability in patients with metastatic breast cancer (MBC), and evaluate its predictive value for patient survival., Methods: The clinical data of 65 patients who had frozen plasma and planned to change the therapeutic regimen were retrospectively enrolled. Low-coverage whole-genome sequencing of cfDNA was performed to generate the chromosomal instability represented by chromosomal instability (CIN) score., Results: Tumors with diverse status of hormone receptor and HER2 represented diverse chromosomal instability across the whole genome. According to the receiver operating characteristic curve and the statistical distribution, CIN score exceed 3881 was defined as "High". 32 (53.3%) patients with high CIN score had similar clinicopathologic characteristics compared with low CIN score patients. The median overall survival of patients with high CIN score was 21.2 months (95% CI 14.1-28.3), which was significantly inferior to those with low CIN score (not reached, P = 0.006). Regardless of various treatment regimens, the median progression free survival in patients with high CIN score was 7.3 months, which was significantly worse than those in the low CIN score population (11.0 months, P = 0.034). Multivariate analysis revealed that CIN score was an independent prognostic factor, with hazard ratio of 3.563 (P = 0.005)., Conclusions: To our knowledge, this is the first study illustrating the prognostic value of chromosomal instability derived from cfDNA in MBC., Competing Interests: Declaration of competing interest Ziliang Qian is a salaried employee of Prophet Genomics Inc., a provider of cancer genome-based diagnostic testing. The remaining authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: We performed a retrospective study on the efficacy and safety of sirolimus (an mTOR inhibitor) in hormone receptor (HR)-positive advanced breast cancer and searched for biomarkers to predict its efficacy., Methods: All patients with HR-positive metastatic breast cancer treated with sirolimus plus endocrine therapy between December 2017 and July 2018 at the Cancer Hospital, Chinese Academy of Medical Sciences were consecutively and retrospectively reviewed. Mutations in circulating tumour DNA (ctDNA) were assayed for 1021 tumour-related genes via gene panel target capture-based next-generation sequencing., Results: Thirty-six patients with metastatic breast cancer treated with sirolimus plus endocrine therapy were included. The progression-free survival (PFS) rates between the sirolimus group and everolimus group were similar, and the median PFS was 4.9 months and 5.5 months, respectively (hazard ratio 1.56, 95% CI 0.86-2.81, P = 0.142). The objective response rate in the 36 patients was 19.4%, and the clinical benefit rate was 41.7%. Lipid metabolism disorder was the most common adverse event (69.4%), and 13.9% of patients had stomatitis. Most (94.4%) adverse events were grade 1-2. Twenty patients (55.6%) underwent ctDNA analysis before receiving sirolimus therapy. For patients who received less than 3 lines of chemotherapy, those with PI3K/Akt/mTOR pathway alterations had a better response to sirolimus than those without alterations, with a median PFS of 7.0 months vs 4.3 months (hazard ratio = 0.01, 95% CI 0.00-0.34, P = 0.010)., Conclusions: Sirolimus is a potentially effective treatment option for patients with HR-positive advanced breast cancer., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Human epidermal growth factor receptor 2(HER2) status is a crucial predictive factor for prognostic assessment and targeted therapy selection, which may be influenced by intratumor heterogeneity and molecular divergence between the primary site and different metastases. Therefore, we performed a prospective study to confirm the concordance of HER2 amplification in circulating tumor DNA(ctDNA) with primary tumor tissue and verified its clinical implications., Methods: A total of 105 breast cancer patients were enrolled, and dynamic monitoring of HER2 copy numbers in ctDNA was conducted in 31 participants during the treatment. Totally 186 plasma samples were prospectively obtained and blinded to test HER2 copy numbers in ctDNA based on low-coverage whole genome sequencing(WGS) by next-generation sequencing(NGS)., Results: Comparing HER2 copy numbers in ctDNA collected before the initiation of next line of anticancer treatment with primary tumor tissue, the concordant rate of HER2 amplification was 86.5%(χ 2  = 52.901, p < 0.001), with a positive and negative predictive value of 94.9% and 80.7%, respectively. Histopathologically positive, high-level amplification of HER2 copy numbers in the baseline was significantly correlated with best objective response during the anticancer therapy(p = 0.010). Moreover, HER2 copy numbers fluctuated with HER2-targeted therapeutic response, and the patients with a constantly positive level after 6 weeks of treatment appeared to suffer from significantly reduced progression free survival(p < 0.001)., Conclusions: HER2 amplification in ctDNA, with a concordance rate of over 80% with primary tumors, may be a predictive index for prognostic evaluation and therapeutic response monitoring in a noninvasive, repeatable and practical method for breast cancer patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)