Background: The prognostic value of the tumor burden score (TBS) in patients with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) remains unknown. This study aimed to investigate the impact of TBS on long-term outcomes after surgery.Methods: Patients who underwent radical-intent resection between June 2013 and December 2019 were retrospectively reviewed. Kaplan–Meier curves were used to analyze patient survival, and disease-free survival (DFS) and overall survival (OS) were examined in relation to TBS.Results: A total of 178 patients were included in this study, with 119 in the training cohort and 59 in the validation cohort. Kaplan–Meier curves showed that TBS was a strong prognostic indicator in patients with cHCC-CCA. Elevated TBS was associated with poorer DFS and OS (both P-value < 0.001) and was identified as an independent prognostic indicator. In addition, the prognostic value of TBS outperformed tumor size and number alone, microvascular invasion, and lymph node invasion. The prognostic significance of TBS was confirmed by the internal validation cohort.Conclusions: The present study suggested the significance of tumor morphology in assessing the prognosis of patients with cHCC-CCA who undergoing curative resection. The TBS is a promising prognostic index in patients with cHCC-CCA. Elevated TBS was related to a lower long-term survival rate and was identified as an independent risk factor for poor DFS and OS. Further research is needed to verify our results.

Estrogen receptor-positive (ER+) breast cancer (BC) is a common subtype of BC with a relatively good prognosis. However, recurrence and death from ER+ BC occur because of tumor heterogeneity. This study aimed to explore tumor heterogeneity using next-generation sequencing (NGS) and tumor-organoid models to promote BC precise therapy. We collected needle biopsy, surgical excision, and cerebrospinal fluid (CSF) samples to establish tumor organoids. We found that the histological characteristics of organoids were consistent with original lesions and recapitulated their heterogenicity. In addition, the NGS results showed that PIK3CA and TP53 genes had detrimental mutations. BAP1, RET, AXIN2, and PPP2R2A genes had mutations with unknown function. The score for homologous recombination deficiency (HRD) of genome was 56, indicating that the tumor was likely sensitive to PARPi. The mutant-allele tumor heterogeneity (MATH) value of the tumor genome was 68.03, indicating high tumor heterogeneity. At last, we performed a drug screening on organoids. The toxicity of different drugs toward BC organoids originated from needle biopsy and surgical excision was tested, respectively. The IC₅₀ values in the needle biopsy groups were paclitaxel 2.83μM, carboplatin 61.47μM, neratinib 0.8μM, lapatinib >100μM; in the surgical excision groups: trastuzumab >100μM, docetaxel 0.036μM, tamoxifen 20.54μM, olaparib 5.478μM, BYL719<0.1μM. The toxicity data showed that the BC organoids could show dynamic characteristics of tumor progression and reflect the heterogeneity of BC. Our study demonstrates that the combined use of tumor organoids and NGS is a potential way to test tumor heterogeneity and predict drug response in ER+BC, which contributes to the development of personalized therapy.

Background: Clinical tools for predicting prognosis are limited for patients with hepatocellular carcinoma (HCC) undergoing hepatic arterial infusion chemotherapy (HAIC)-based hepatectomy. This study evaluated the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) in patients with HCC who received HAIC-based hepatectomy. Methods: This dual-center retrospective study included 390 patients who received HAIC-based conversion resection to investigate the relationship of NLR and LMR with survival outcomes, adverse events, and risk factors. Results: A total of 390 patients with HCC who received HAIC-based conversion liver resection were included. Patients with NLR ≥ 5 exhibited a significantly shorter overall survival (OS) and recurrence-free survival (RFS) compared to those with NLR < 5 (P = 0.0181 and P = 0.0164, respectively). Patients with LMR ≥ 3 exhibited favorable OS and RFS rates compared to those with LMR < 3 (P = 0.0195 and P = 0.0225, respectively). Similar results were observed in patients who achieved an objective response. NLR ≥ 5 and LMR < 3 were significantly associated with decreased OS and RFS compared to NLR < 5 and LMR ≥ 3 (P = 0.0131, P = 0.0104, P = 0.0055, and P = 0.0329, respectively). Conclusion: NLR and LMR have an effective predictive capability in prognosis for patients with HCC who received HAIC-based conversion surgery. These findings may help surgeons and patients make decisions regarding HAIC-based conversion hepatectomy. Plain Language Summary: Patients with NLR ≥ 5 and LMR < 3 exhibited a significantly shorter OS and RFS than those with NLR < 5 and LMR ≥ 3. NLR≥ 5 and LMR< 3 were significantly associated with decreased OS and RFS compared to NLR < 5 and LMR ≥ 3 for patients who achieved an objective response. Our findings may be useful in guiding surgeons and patients in decision-making regarding HAIC-based conversion hepatectomy.

An amendment to this paper has been published and can be accessed via the original article.