Hadidi, Danny

Objectives: Anaplastic thyroid cancer (ATC) is a rare and aggressive type of thyroid malignancy with a very poor prognosis and outcome despite therapy. The rarity of this disease and the poor functional status of ATC patients limit the ability to conduct clinical trials, thus there is a lack of large, controlled trials to guide treatment and evaluate the benefit of combined modality therapy. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with ATC at age 18 or older between 2004 and 2018. After excluding patients with unknown number of treatment modalities, Charlson-Deyo score—a weighted summary of 17 chronic disease categories where higher scores denote greater baseline comorbidity burden—of 3 or more and patients lost for follow-up, we split the cohort into 3 groups according to the number of treatment modalities they received. Treatment modalities included surgery, radiation, and systemic therapy. Then, we evaluated the overall survival (OS) between the 3 groups. We studied the OS using Kaplan-Meier estimates and multivariate Cox regression analyses to evaluate factors associated with OS. In addition, propensity score matching (accounting for age, sex, race, Charlson-Deyo score, and clinical M stage) was used for more robust results. Results: A total of 3460 patients with ATC were included in the analysis, of which 1472 (42.5%) either received one type of therapy or did not receive any therapy (group 1), 1092 (31.6%) received bimodal therapy (group 2), and 896 (25.9%) received trimodal therapy (group 3). We found that group 3 had better OS compared with group 1 and group 2 (median OS 9.1 vs. 1.7 and 4.9 mo, respectively, with P <0.001 for all comparisons). Propensity score matching yielded 896 patients in each group. We found that group 3 had better OS compared with group 1 and group 2 (median OS 9.1 vs. 1.9 and 5.2 mo, respectively, with P <0.001 for all comparisons). Same trend was found in subgroup analysis when we split the cohort according to the metastatic status; in M0 group (median OS was 10.4 vs. 1.9 and 6.1 mo, respectively, with P <0.001 for all), in M1 group (median OS was 5.9 vs. 1.4 and 3.7 mo, respectively, with P <0.001 for all). Modality-specific analyses further demonstrated that surgery, radiation, and systemic therapy each independently prolonged OS in both M0 and M1 cohorts (all P <0.001). These individual benefits explain the additive advantage of trimodal therapy and underscore that offering at least one evidence-based modality is preferable when comprehensive treatment is infeasible. On multivariate analysis, group 1 and group 2 were associated with worse OS compared with trimodal treatment (HR: 2.721; 95% CI: 2.466-3.002 and HR: 1.434; 95% CI: 1.299-1.582, P <0.001 for all). Conclusions: Patients with ATC who were treated with intensive trimodal therapy had statistically significant improvement in OS compared with patients who received less intense therapy. This survival benefit was observed in both metastatic and nonmetastatic groups. Although we acknowledge the limitations of this retrospective analysis, our results showed the critical role of an intensive therapy approach in this aggressive malignancy.

Objectives: Hepatocellular carcinoma (HCC) is the most common type of liver malignancy and the third leading cause of cancer-related death in the world. Liver transplant is a cornerstone in treating nonmetastatic disease, but a significant portion of patients miss the opportunity of upfront liver transplant given the long waiting time for donor organs. Herein, we compare the survival outcomes between upfront liver transplant, liver transplant with bridge systemic therapy, and systemic therapy only. Methods: The National Cancer Database was queried for patients diagnosed with non-metastatic hepatocellular carcinoma (HCC) between 2004 and 2017. After including only patients with clinical N0 stage who received either systemic therapy alone, liver transplant alone or liver transplant with bridge systemic therapy, we split the cohort into 3 groups: systemic therapy only (including intra-arterial chemotherapy eg, TACE) group, upfront liver transplant group and liver transplant with bridge systemic therapy group. We evaluated overall survival (OS) among the three groups. We studied the OS using Kaplan-Meier estimates and multivariate Cox regression analyses to evaluate factors associated with overall survival (OS). Results: A total of 29,691 patients with nonmetastatic HCC were included for analysis, of which 25,122 (84.6%) were treated with systemic therapy only, 2513 (8.5%) were treated with bridge systemic therapy followed by liver transplant, and 2056 (6.9%) were treated with upfront liver transplant without systemic therapy bridge. We found that patients who were treated with bridge systemic therapy followed by liver transplant and patients who were treated with upfront liver transplant had a statistically significantly better OS compared to patients who were treated with systemic therapy only (mean OS was 101.9 mo and 98.2 vs. 39.4 mo, respectively, with P <0.001 for all). Whereas there was no significant difference in OS between patients who were treated with bridge systemic therapy followed by liver transplant and patients who were treated with upfront liver transplant (mean OS was 101.9 vs. 98.2 months, P =0.187). On multivariate analysis, factors associated with worse OS were older age (HR: 1.011; 95% CI: 1.010-1.013; P <0.001), Male sex (HR: 1.048; 95% CI: 1.014-1.084; P =0.006), White compared with African American race (HR: 1.055; 95% CI: 1.012-1.099; P =0.011), no insurance status (HR: 1.155; 95% CI: 1.079-1.237; P <0.001), clinical T4 stage compared with T0 stage (HR: 1.366; 95% CI: 1.257-1.483, P <0.001), and systemic therapy alone compared with upfront liver transplant and liver transplant with bridge systemic therapy (HR for upfront liver transplant and transplant with bridge systemic therapy vs. systemic therapy was 0.202; 95% CI: 0.184-0.223, and HR: 0.194, 95% CI: 0.178-0.212, respectively, with P <0.001 for all). Conclusions: Patients with nonmetastatic HCC who were treated with upfront liver transplant or liver transplant with bridge systemic therapy had statistically significant improvement in OS compared with patients who were treated with systemic therapy only. While our study confirms the survival benefit of liver transplant among patients with nonmetastatic HCC, these results raise the importance of proceeding with liver transplant after intra-arterial and/or systemic treatments in patients who are not initially eligible for or missed the opportunity of upfront liver transplant.