Development of a Novel Comprehensive Hepatocellular Carcinoma Outcome Prognostic Scoring System With Integration of Imaging Features.

BACKGROUND: Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems. METHODS: Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of covariates that impacted OS and a validation set. Cox models were used to determine the association of various factors with OS and a scoring system was created. RESULTS: We identified 383 patients with HCC with imaging and survival outcomes, n = 255 in the training set and 128 in the validation cohort. Factors associated with OS on multivariate analysis included: tumor margin appearance on CT or MRI (hazard ratio [HR] 1.37, 95% CI, 1.01-1.88) with infiltrative margins portending worse outcomes than encapsulated margins, massive tumor morphology (HR 1.64, 95% CI, 1.06-2.54); >2 lesions (HR 2.06, 95% CI, 1.46-2.88), Child-Turcotte-Pugh class C (HR 3.7, 95% CI, 2.23-6.16), and portal vein thrombus (HR 2.41, 95% CI, 1.71-3.39). A new scoring system was developed and more predictive of OS than other well-established systems. CONCLUSIONS: Incorporation of standardized imaging characteristics to established clinical and lab predictors of outcome resulted in an improved predictive scoring system for patients with HCC.

Local therapy reduces the risk of liver failure and improves survival in patients with intrahepatic cholangiocarcinoma: A comprehensive analysis of 362 consecutive patients.

BACKGROUND: Treatment methods for intrahepatic cholangiocarcinoma (ICC) have improved, but their impact on outcome remains unclear. We evaluated the outcomes of patients definitively treated with resection, radiation, and chemotherapy for ICC, stratified by era. METHODS: Clinico-pathologic characteristics, cause of death, disease-specific survival (DSS), and intrahepatic progression-free survival (IPFS) were compared among patients who underwent resection, radiation, or chemotherapy as definitive treatment strategies for ICC (without distant organ metastasis) between 1997 and 2015. Variables were also analyzed by era (1997-2006 [early] or 2007-2015 [late]) within each group. RESULTS: Among 362 patients in our cohort, 122 underwent resection (early, 38; late, 84), 85 underwent radiation (early, 17; late, 68), and 148 underwent systemic chemotherapy alone (early, 51; late, 97) as definitive treatment strategies, and 7 patients received best supportive care. In the resection group, the 3-year DSS rate was 58% for the early era and 67% for the late era (P = .036), and the 1-year IPFS was 50% for the early era and 75% for the late era (P = .048). In the radiation group, the 3-year DSS was 12% for the early era and 37% for the late era (P = .048), and the 1-year IPFS was 48% for the early era and 64% for the late era (P = .030). In the chemotherapy group, DSS and IPFS did not differ by era. Patients treated with chemotherapy developed liver failure at the time of death significantly more frequently than patients treated with resection (P < .001) or radiation (P < .001). Multivariable analysis identified local therapy (resection or radiation) as a sole predictor of death without liver failure. CONCLUSION: Survival outcomes have improved for local therapy-based definitive treatment strategies for ICC, which may be attributable to maintaining control of intrahepatic disease, thereby reducing the occurrence of death due to liver failure. Cancer 2017;123:1354-1362. © 2016 American Cancer Society.

Enhancement Pattern Mapping for Early Detection of Hepatocellular Carcinoma in Patients with Cirrhosis.

Background and Aims: Limited methods exist to accurately characterize the risk of malignant progression of liver lesions. Enhancement pattern mapping (EPM) measures voxel-based root mean square deviation (RMSD) of parenchyma and the contrast-to-noise (CNR) ratio enhances in malignant lesions. This study investigates the utilization of EPM to differentiate between HCC versus cirrhotic parenchyma with and without benign lesions. Methods: Patients with cirrhosis undergoing MRI surveillance were studied prospectively. Cases (n=48) were defined as patients with LI-RADS 3 and 4 lesions who developed HCC during surveillance. Controls (n=99) were patients with and without LI-RADS 3 and 4 lesions who did not develop HCC. Manual and automated EPM signals of liver parenchyma between cases and controls were quantitatively validated on an independent patient set using cross validation with manual methods avoiding parenchyma with artifacts or blood vessels. Results: With manual EPM, RMSD of 0.37 was identified as a cutoff for distinguishing lesions that progress to HCC from background parenchyma with and without lesions on pre-diagnostic scans (median time interval 6.8 months) with an area under the curve (AUC) of 0.83 (CI: 0.73-0.94) and a sensitivity, specificity, and accuracy of 0.65, 0.97, and 0.89, respectively. At the time of diagnostic scans, a sensitivity, specificity, and accuracy of 0.79, 0.93, and 0.88 were achieved with manual EPM with an AUC of 0.89 (CI: 0.82-0.96). EPM RMSD signals of background parenchyma that did not progress to HCC in cases and controls were similar (case EPM: 0.22 ± 0.08, control EPM: 0.22 ± 0.09, p=0.8). Automated EPM produced similar quantitative results and performance. Conclusion: With manual EPM, a cutoff of 0.37 identifies quantifiable differences between HCC cases and controls approximately six months prior to diagnosis of HCC with an accuracy of 89%.

Current surveillance and diagnostic methods in hepatocellular carcinoma are suboptimal. Enhancement pattern mapping is an imaging technique that quantifies lesion signals and may be useful in diagnostic and surveillance methods. Enhancement pattern mapping describes quantifiable differences between malignant and benign liver tissue on contrast-enhanced MRI. It amplifies lesion signal and distinguishes malignancy in a surveillance population. The novel imaging technique was investigated at single institution and analyzed lesions compared to cirrhotic parenchyma. Future efforts will include further risk stratification across LI-RADS group categories. The results provide evidence that enhancement pattern mapping uses available imaging data to distinguish hepatocellular carcinoma from non-cancerous parenchyma with and without benign lesions on scans six months prior to diagnosis with standard MRI. The technique introduces a prospective modality to improve diagnostic accuracy and early detection with the goal of improving clinical outcomes.

Outcomes and Toxicities of Modern Combined Modality Therapy with Atezolizumab Plus Bevacizumab and Radiation Therapy for Hepatocellular Carcinoma.

Atezolizumab plus bevacizumab has become frontline therapy for unresectable HCC. The compatibility of atezolizumab/bevacizumab with liver-directed RT has not been reported. Methods: HCC patients treated with liver-directed RT and atezolizumab/bevacizumab between 1/2020−11/2021 were included. Toxicity and outcomes were retrospectively recorded. For ALCs, we matched the analysis to a previously cohort of RT-treated HCC patients who did not receive atezolizumab/bevacizumab. Survival and time-to-liver-failure were analyzed using Kaplan−Meier. Results: Of 21 patients, with a median follow-up of 9.5 months, the median OS was 16.1 months. Post-RT, all patients had reduced tumors or treatment response. There were no ≥Grade 3 RT-related toxicities. Autoimmune complications occurred in two patients (9.5%), and GI bleeding in three patients (14.3%). Liver function remained stable post-RT. There was a marked decrease in ALCs immediately post-RT (post-RT/pre-RT ratio 47.3%, p < 0.0001), restored by 1 month to pre-treatment baseline (1-month post-RT/pre-RT ratio 95.1%, n.s.). Compared to HCC patients treated with RT alone, post-RT ALC recovery was faster with atezolizumab/bevacizumab (p = 0.009). Conclusion: In this first reported experience of RT with modern systemic therapy for HCC, combination therapy is safe and well-tolerated. As a favorable prognosticator, there appears to be faster recovery of ALC among patients who received RT with atezolizumab/bevacizumab.

Benchmarking Outcomes for Definitive Treatment of Young-Onset, Locally Advanced Rectal Cancer.

PURPOSE: There has been an increase in the incidence of rectal cancer diagnosed in young adults (age < 50 years). We evaluated outcomes among young adults treated with pre-operative long course chemoradiation (CRT) and total mesorectal excision (TME). METHODS: The medical records of 219 patients, age 18-49, with non-metastatic, cT3-4, or cN1-2 rectal adenocarcinoma treated from 2000 to 2017 were reviewed for demographic and treatment characteristics, as well as pathologic and oncologic outcomes. The Kaplan-Meier test, log-rank test, and Cox regression analysis were used to evaluate survival outcomes. RESULTS: The median age at diagnosis was 44 years. CRT followed by TME and post-operative chemotherapy was the most frequent treatment sequence (n = 196), with FOLFOX (n = 115) as the predominant adjuvant chemotherapy. There was no difference in sex, stage, MSS/pMMR, or pCR by age (< 45 years [n = 111] vs. ≥ 45 years [n = 108]). The 5-year rates of DFS were 77.2% for all patients, 69.8% for age < 45 years and 84.7% for age ≥ 45 years (P = .01). The 5-year rates of OS were 89.6% for all patients, 85.1% for patients with age < 45 years and 94.3% for patients with age ≥ 45 years (P = .03). Age ≥ 45 years was associated with a lower risk of disease recurrence or death on multivariable Cox regression analysis (HR = 0.55, 95% CI 0.31-0.97, P = .04). CONCLUSION: Among young adults, patients with age < 45 years had lower rates of DFS and OS, compared to those with age ≥ 45 years. These outcomes could serve as a benchmark by which to evaluate newer treatment approaches.

Implementation of a Novel Web-Based Lesion Selection Tool to Improve Acquisition of Tumor Biopsy Specimens.

Introduction: For maximum utility of molecular characterization by next-generation sequencing (NGS) and better understanding of tumor microenvironment with immune correlates analysis, biopsy specimens must yield adequate tumor tissue, and sequential biopsy specimens should sample a consistent site. We developed a web-based lesion selection tool (LST) that enables management and tracking of the biopsy specimen collections. Methods: Of 145 patients, the LST was used for 88 patients; the other 57 served as controls. We evaluated consistency of the lesion biopsied in longitudinal collections, number of cores obtained, and cores with adequate tumor cellularity for NGS. The Fisher exact test and Wilcoxon rank sum test were used to identify differences between the groups. Results: The analysis included 30 of 88 (34%) patients in the LST group and 52 of 57 (91%) in the control group. The LST workflow ensured 100% consistency in the lesions biopsied compared with 75% in the control group in longitudinal collections and increased the proportion of patients in whom at least five cores were collected per biopsy. Conclusions: The novel LST platform facilitates coordination, performance, and management of longitudinal biopsy specimens. Use of the LST enables sampling of the designated lesion consistently, which is likely to accurately inform us the effect of the treatment on tumor microenvironment and evolution of resistant pathways. Such studies are important translational component of any clinical trials and research as they guide the development of next line of therapy, which has significant effect on clinical utility. However, validation of this approach in a larger study is warranted.