Translating imaging traits of mass-forming intrahepatic cholangiocarcinoma into the clinic: From prognostic to therapeutic insights.

Background & Aims: The progress toward clinical translation of imaging biomarkers for mass-forming intrahepatic cholangiocarcinoma (MICC) is slower than anticipated. Questions remain on the biologic behaviour underlying imaging traits. We developed and validated imaging-based prognostic systems for resected MICCs with an appraisal of the tumour immune microenvironment (TIME) underpinning patient-specific imaging traits. Methods: Between January 2009 and December 2019, a total of 322 patients who underwent dynamic computed tomography/magnetic resonance imaging and curative-intent resection for MICC at three hepatobiliary institutions were retrospectively recruited, divided into training (n = 193) and validation (n = 129) datasets. Two radiological and clinical scoring (RACS) systems, one integrating preoperative variables and one integrating preoperative and postoperative variables, were developed using Cox regression analysis. We then prospectively analysed the TIME of tissue samples from 20 patients who met study criteria from January 2021 to December 2021 using multiplexed immunofluorescence. Results: Preoperative and postoperative MICC-RACS systems built on carbohydrate antigen 19-9, albumin, tumour number, radiological/pathological nodal status, pathological necrosis, and three radiological traits (arterial enhancement pattern, tumour boundary, and capsular retraction) demonstrated good performance in predicting disease-specific (C-statistic >0.80) and disease-free (C-statistic >0.75) survival that outperformed rival models and staging systems across study cohorts (P <0.05 for all). Patients with MICC-RACS score of 0-2 (low risk), 3-5 (medium risk), and ≥6 (high risk) had incrementally worse prognosis after surgery. Significant differences in spatial distribution and infiltration level of immune cells were identified between arterial enhancement patterns. Enhanced infiltration of immunosuppressive regulatory T cells and M2-like macrophages at the invasive margin were noted in tumours with distinct boundary and capsular retraction, respectively. Conclusions: Our MICC-RACS systems are simple but powerful prognostic tools that may facilitate the understanding of spatially distinct TIMEs and patient-tailored immunotherapy approach. Impact and Implications: The progress toward clinical translation of imaging biomarkers for mass-forming intrahepatic cholangiocarcinoma (MICC) is slower than anticipated. Questions remain on the biologic behaviour of MICC underlying imaging traits. In this study, we proposed novel and easy-to-use tools, built on radiological and clinical features, that demonstrated good performance in predicting the prognosis either before or after surgery and outperformed rival models/systems across major imaging modalities. The characteristic radiological traits integrated into prognostic systems (arterial enhancement pattern, tumour boundary, and capsular retraction) were highly correlated with heterogeneous tumour-immune microenvironments, thereby renovating treatment paradigms for this difficult-to-treat disease.

Development and validation of a gradient boosting machine to predict prognosis after liver resection for intrahepatic cholangiocarcinoma.

BACKGROUND: Accurate prognosis assessment is essential for surgically resected intrahepatic cholangiocarcinoma (ICC) while published prognostic tools are limited by modest performance. We therefore aimed to establish a novel model to predict survival in resected ICC based on readily-available clinical parameters using machine learning technique. METHODS: A gradient boosting machine (GBM) was trained and validated to predict the likelihood of cancer-specific survival (CSS) on data from a Chinese hospital-based database using nested cross-validation, and then tested on the Surveillance, Epidemiology, and End Results (SEER) database. The performance of GBM model was compared with that of proposed prognostic score and staging system. RESULTS: A total of 1050 ICC patients (401 from China and 649 from SEER) treated with resection were included. Seven covariates were identified and entered into the GBM model: age, tumor size, tumor number, vascular invasion, number of regional lymph node metastasis, histological grade, and type of surgery. The GBM model predicted CSS with C-Statistics ≥ 0.72 and outperformed proposed prognostic score or system across study cohorts, even in sub-cohort with missing data. Calibration plots of predicted probabilities against observed survival rates indicated excellent concordance. Decision curve analysis demonstrated that the model had high clinical utility. The GBM model was able to stratify 5-year CSS ranging from over 54% in low-risk subset to 0% in high-risk subset. CONCLUSIONS: We trained and validated a GBM model that allows a more accurate estimation of patient survival after resection compared with other prognostic indices. Such a model is readily integrated into a decision-support electronic health record system, and may improve therapeutic strategies for patients with resected ICC.

Surgical Strategy for Resecting Hepatocellular Carcinoma in the Caudate Lobe: Isolated or Combined Lobectomy? A Single-Center Study and Meta-Analysis.

BACKGROUND: Resection of hepatocellular carcinoma (HCC) originating in the caudate lobe remains challenging, while the optimal extent of resection is debated. We aimed to evaluate the relative benefits of combined caudate lobectomy (CCL) versus isolated caudate lobectomy (ICL) for caudate HCC. METHODS: Patients who underwent curative-intent resection for caudate HCC between January 2010 and December 2018 were identified from a single-center database. Surgical outcomes of the two strategy groups were analyzed before and after propensity score matching. A systematic review with meta-analysis was also performed to compare outcomes of CCL versus ICL for caudate HCC. RESULTS: A total of 28 patients were included: 11 in the CCL and 17 in the ICL group. Compared with ICL, the CCL group contained patients with larger tumors and a higher incidence of vascular invasion. After propensity score matching, 6 pairs of patients were selected. In the well-matched cohort, CCL demonstrated significantly improved recurrence-free survival (RFS) (P = 0.047) compared with ICL; no significant differences were noted for overall survival (OS), operation time, blood loss and morbidity rate. A total of 227 patients from nine eligible studies and ours were involved in the systematic review. Meta-analysis revealed that CCL provided better RFS (hazard ratio 0.54, 95% confidence interval 0.31-0.92) than ICL; no significant differences were observed in OS, operation time, blood loss and morbidity rate. CONCLUSION: CCL confers superior RFS over ICL without compromise of perioperative outcomes and should be prioritized for patients with caudate HCC when feasible, especially for those with large-sized tumors.

[Selective neck dissection in the management of tongue squamous cell carcinoma with clinically negative nodes].

OBJECTIVE: To compare the effectiveness of selective neck dissection (SND) with radical or modified radical neck dissection (RND) for the management of tongue squamous cell carcinoma with clinically negative nodes (cN0). METHODS: There were 33 patients who were treated with SND (including 14 supraomohyoid neck dissection and 19 level I -IV neck dissection ) between January 1998 and December 2002. According to T classifications, treatment modality and pathological status of lymph node (pN), the control group of 33 patients were randomly selected from the cN0 tongue squamous cell carcinoma patients who were treated with RND between January of 1980 and December of 1997. Kaplan-Meier was used to calculate the rate of regional recurrence and 5-year survival rate. RESULTS: The neck recurrent for RND population was 9.1% (3 patients), which was not statistically different from the neck recurrent in the SND population 12.1% (4 patients). Also, the 5-year survival rates were no statistic difference between SND and RND groups (82.9%, 28 patients vs 78.8%, 26 patients). The rate of recurrent outside the dissection area for level I -IV neck dissection population was 0, which was statistically different from the rate of recurrent outside the dissection area in the supraomohyoid neck dissection population (14.3%, 2 patients). CONCLUSIONS: Comparing to the radical or modified neck dissection, the SND offered the same oncologic compromise for patients with cN0 tongue squamous cell carcinoma. I -IV neck dissection was recommended.