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Ali A. Mokdad, Amit G. Singal, Jorge A. Marrero, Hao Zhu, and Adam C. Yopp

Background: Patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) have variable long-term outcomes. Better delineation of prognosis is important for clinical trial enrollment and clinical practice in an era of precision medicine. We hypothesized that stratification of patients with BCLC stage C HCC by presence of vascular invasion and/or metastasis improves prognostic discrimination. Methods: Using a prospectively maintained database, we identified 234 patients diagnosed with BCLC stage C HCC between 2005 and 2015. Patients were stratified into 3 groups based on tumor characteristics: (1) vascular invasion alone, (2) metastasis alone, and (3) vascular invasion and metastasis. Overall survival (OS) was compared using a Cox model. A subgroup analysis was performed based on extent of vascular invasion and site of metastasis. Results: The cohort comprised 123 patients (53%) with vascular invasion alone, 34 (15%) with metastasis alone, and 77 (33%) with both vascular invasion and metastasis. Median survival was 5.7, 3.9, and 3.0 months, respectively (P<.01). Patients with vascular invasion or metastasis alone had significantly better survival compared with those with vascular invasion and metastasis (adjusted hazard ratio [HR],0.68; 95% CI, 0.49–0.94, and HR, 0.61; 95% CI, 0.39–0.96, respectively). Compared with tumoral invasion of branch portal veins, involvement of the main portal vein was associated with worse survival (HR, 2.13; 95% CI, 1.29–3.49). OS did not differ by site of metastasis. Conclusions: Stratification of patients within the BCLC stage C staging subgroup by vascular invasion and presence of metastasis further discriminates patient prognosis. This substratification may have implications for therapy and more accurate prognostic features.

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Ali Mokdad, Travis Browning, John C. Mansour, Hao Zhu, Amit G. Singal, and Adam C. Yopp

Background: The diagnosis and treatment of cancer is a continuum, with multiple steps and interfaces between patients and providers allowing for potential delays in cancer recognition and subsequent treatment. The diagnosis and treatment of hepatocellular carcinoma (HCC) is especially prone to missteps along the continuum, leading to treatment delays due to non–tissue-based diagnosis and multiprovider treatments. The aim of this study was to evaluate outcome measures after implementation of a voice messaging system (VMS) designed to streamline patient referrals to downstream treatment physicians and ultimately reduce delays in HCC treatment, thereby improving outcome measures. Methods: A retrospective study of outpatients with HCC was conducted in a safety net hospital between February 2008 and January 2012. In February 2010, VMS notification of HCC to the ordering physician and downstream treating physicians was implemented. Patients were divided into 2 groups: (1) preintervention: diagnosis 2 years before implementation or failure of notification following implementation, and (2) postintervention: diagnosis 2 years after implementation. Demographics, tumor characteristics, treatment, and survival were compared. Results: This study included 96 patients diagnosed with HCC: 51 in the preintervention group and 45 in the postintervention group. The main cause of chronic liver disease was HCV infection, and no differences in symptoms, liver dysfunction, tumor characteristics, or treatment were observed between groups. The time from diagnosis to clinic contact (0.5 vs 2.9 months; P=.003) and time from detection to treatment (2.2 vs 5.5 months; P=.005) was significantly shorter after implementation of the VMS. Barcelona Clinic Liver Cancer stage A status (hazard ratio [HR], 3.1; 95% CI, 2, 6), treatment (HR, 1.9; 95% CI, 1, 4), and VMS (HR, 1.8; 95% CI, 1, 3) were independently associated with overall survival. Patients diagnosed after implementation of the VMS had a median survival of 28.5 versus 15.7 months (P=.02). Conclusions: Implementation of VMS reduces time to treatment and time to clinic visit. Reduction in time to treatment is associated with improved outcome independent of tumor stage, underlying liver function, and treatment.

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Yao Zhu, Yu Wei, Hao Zeng, Yonghong Li, Chi-Fai Ng, Fangjian Zhou, Caiyun He, Guangxi Sun, Yuchao Ni, Peter K.F. Chiu, Jeremy Y.C. Teoh, Beihe Wang, Jian Pan, Fangning Wan, Bo Dai, Xiaojian Qin, Guowen Lin, Hualei Gan, Junlong Wu, and Dingwei Ye

Background: Although China accounts for 7.8% of worldwide new prostate cancer (PCa) cases and 14.5% of new deaths according to GLOBOCAN 2020, the risk of PCa associated with germline mutations is poorly defined, hampered in part by lack of nationwide evidence. Here, we sequenced 19 PCa predisposition genes in 1,836 Chinese patients with PCa and estimated disease risk associated with inherited mutations. Patients and Methods: Patients were recruited from 4 tertiary cancer centers (n=1,160) and a commercial laboratory (n=676). Germline DNA was sequenced using a multigene panel, and pathogenic/likely pathogenic (P/LP) mutation frequencies in patients with PCa were compared with populations from the gnomAD (Genome Aggregation Database) and ChinaMAP (China Metabolic Analytics Project) databases. Clinical characteristics and progression-free survival were assessed by mutation status. Results: Of 1,160 patients from hospitals, 89.7% had Gleason scores ≥8, and 65.6% had metastases. P/LP mutations were identified in 8.49% of Chinese patients with PCa. Association with PCa risk was significant for mutations in ATM (odds ratio [OR], 5.9; 95% CI, 3.1–11.1), BRCA2 (OR, 15.3; 95% CI, 10.0–23.2), MSH2 (OR, 15.8; 95% CI, 4.2–59.6), and PALB2 (OR, 5.9; 95% CI, 2.7–13.2). Compared with those without mutations, patients with mutations in ATM, BRCA2, MSH2, or PALB2 showed a poor outcome with treatment using androgen deprivation therapy and abiraterone (hazard ratio, 2.19 [95% CI, 1.34–3.58] and 2.47 [95% CI, 1.23–4.96], respectively) but similar benefit from docetaxel. Conclusions: The present multicenter study confirmed that a significant proportion of Chinese patients with PCa had inherited mutations and identified predisposition genes in this underreported ethnicity. These data provide empirical evidence for precision prevention and prognostic estimation in Chinese patients with PCa.

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Yao Zhu, Yu Wei, Hao Zeng, Yonghong Li, Chi-Fai Ng, Fangjian Zhou, Caiyun He, Guangxi Sun, Yuchao Ni, Peter K.F. Chiu, Jeremy Y.C. Teoh, Beihe Wang, Jian Pan, Fangning Wan, Bo Dai, Xiaojian Qin, Guowen Lin, Hualei Gan, Junlong Wu, and Dingwei Ye

Background: Although China accounts for 7.8% of worldwide new prostate cancer (PCa) cases and 14.5% of new deaths according to GLOBOCAN 2020, the risk of PCa associated with germline mutations is poorly defined, hampered in part by lack of nationwide evidence. Here, we sequenced 19 PCa predisposition genes in 1,836 Chinese patients with PCa and estimated disease risk associated with inherited mutations. Patients and Methods: Patients were recruited from 4 tertiary cancer centers (n=1,160) and a commercial laboratory (n=676). Germline DNA was sequenced using a multigene panel, and pathogenic/likely pathogenic (P/LP) mutation frequencies in patients with PCa were compared with populations from the gnomAD (Genome Aggregation Database) and ChinaMAP (China Metabolic Analytics Project) databases. Clinical characteristics and progression-free survival were assessed by mutation status. Results: Of 1,160 patients from hospitals, 89.7% had Gleason scores ≥8, and 65.6% had metastases. P/LP mutations were identified in 8.49% of Chinese patients with PCa. Association with PCa risk was significant for mutations in ATM (odds ratio [OR], 5.9; 95% CI, 3.1–11.1), BRCA2 (OR, 15.3; 95% CI, 10.0–23.2), MSH2 (OR, 15.8; 95% CI, 4.2–59.6), and PALB2 (OR, 5.9; 95% CI, 2.7–13.2). Compared with those without mutations, patients with mutations in ATM, BRCA2, MSH2, or PALB2 showed a poor outcome with treatment using androgen deprivation therapy and abiraterone (hazard ratio, 2.19 [95% CI, 1.34–3.58] and 2.47 [95% CI, 1.23–4.96], respectively) but similar benefit from docetaxel. Conclusions: The present multicenter study confirmed that a significant proportion of Chinese patients with PCa had inherited mutations and identified predisposition genes in this underreported ethnicity. These data provide empirical evidence for precision prevention and prognostic estimation in Chinese patients with PCa.