Radiologic Response Combined with Dermatologic Toxicities is the Most Robust Predictor of Survival Benefits in Patients with Inoperable Hepatocellular Carcinoma After Transarterial Chemoembolization Plus Sorafenib Therapy.

PURPOSE: The survival benefits of patients with inoperable hepatocellular carcinoma (HCC) who undergo transarterial chemoembolization (TACE) and receive sorafenib therapy remain controversial. We aimed to identify clinical predictors in patients with inoperable HCC undergoing TACE and receiving sorafenib. METHODS: Between January 2014 and December 2017, 148 consecutive patients with inoperable HCC who were treated with TACE plus sorafenib were retrospectively analyzed. Critical clinical factors associated with overall survival (OS) were identified by Cox regression model analysis. Kaplan-Meier methods were used to calculate the survival times, which were compared with the log-rank test. RESULTS: Macrovascular invasion (MVI), radiologic response and sorafenib-related dermatologic toxicities were identified as independent factors associated with OS. MVI is a known prognostic factor before treatment. The median OS of patients with either radiologic response or dermatologic toxicities was significantly improved compared with that of patients without it (both 23.0 vs. 7.0 months, P < 0.001). The median OS of patients with a combination of radiologic response and dermatologic toxicities was significantly longer than that of patients with either radiologic response or dermatologic toxicities, as well as no response (25.0 vs. 14.0 vs. 6.0 months, respectively, P < 0.001), and the predictive value was confirmed across patients with different baseline characteristics in terms of MVI, α-fetoprotein level, performance status and liver function. CONCLUSION: The combination of radiologic response and sorafenib-related dermatologic toxicities is the most robust predictor of survival benefits for HCC patients after TACE plus sorafenib therapy. LEVEL OF EVIDENCE: Level 3.

The PPRD score stratifies patients with hepatocellular carcinoma and portal vein tumor thrombus treated with sorafenib plus transarterial chemoembolization.

OBJECTIVES: To identify clinical prognostic and predictive factors in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) undergoing sorafenib plus transarterial chemoembolization (TACE) and establish a prognostic score for these patients. METHODS: Between January 2012 and December 2017, 184 consecutive patients with HCC and PVTT were concurrently treated with sorafenib and TACE. Univariate and multivariate analyses were performed to explore the clinical factors independently correlated with overall survival (OS). A prognostic score was then developed to identify different prognoses in an initial cohort and validated in an external cohort (n = 72). RESULTS: In the multivariate analysis, performance status, extension of PVTT, initial radiological response, and sorafenib-related dermatologic toxicity were identified as predictors associated with OS. These factors were used to develop a prognostic score (PPRD score, range from 0 to 11). The median survival was found to decrease as the PPRD score increased, and patients were stratified into a favorable group (0 points), intermediate group (1-4 points), and dismal group (> 4 points). The median survival of patients in the three groups was 34.0 months, 20.0 months, and 7.0 months, respectively (p < 0.001). Additionally, the time to progression (TTP) (p < 0.001) was stratified along the same prognostic groups. The external validation cohort confirmed the prognostic scores. CONCLUSIONS: The proposed score system can accurately stratify the outcomes of patients with HCC and PVTT treated with sorafenib plus TACE to help identify which group of patients may benefit from treatment. KEY POINTS: • The survival benefits of patients with advanced HCC treated with sorafenib plus TACE remains controversial. • The independent factors associated with survival were identified to develop a prognostic score, called the PPRD score (standing for performance status, PVTT grade, radiological response, and sorafenib-related dermatologic toxicity); the median survival decreases as the score increases. • The scoring system can accurately stratify the survival benefits of patients with HCC and PVTT treated with combination therapy and help to identify which group of patients may benefit from the treatment. Graphical abstract.

Clinical Value of 18F-FDG PET/CT in Prediction of Visceral Pleural Invasion of Subsolid Nodule Stage I Lung Adenocarcinoma.

RATIONALE AND OBJECTIVES: This study investigated the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for predicting visceral pleural invasion (VPI) of subsolid nodule (SSN) stage I lung adenocarcinoma. MATERIALS AND METHODS: A retrospective analysis of 18F-FDG PET/CT data from 65 postsurgical cases with surgical pathology-confirmed SSN lung adenocarcinoma identified significant VPI predictors using multivariate logistic regression. RESULTS: Nodule and solid component sizes, solid component-to-tumor ratios, pleural indentations, distances between nodules and pleura, and maximum standardized uptake values (SUVmax) differed significantly between VPI-positive (n = 30) and VPI-negative (n = 35) cases on univariate analysis. The distance between the nodule and pleura and SUVmax were significant independent VPI predictors on multivariate analysis. Areas under the curve of the distance between the nodule and pleura and SUVmax on receiver operating characteristic curves were 0.76 and 0.79, respectively; both factors were 0.90. The area under the curve of combined predictors was significantly superior to the distance between the nodule and pleura only but not SUVmax alone. The threshold of the distance between the nodule and pleura, to predict VPI was 4.50 mm, with 96.67% sensitivity, and 57.14% specificity. The threshold of SUVmax to predict VPI was 1.05, with 100% sensitivity and 60% specificity. The sensitivity and specificity of model 2 using the independent predictive factors were 96.67%, and 71.43%, respectively. CONCLUSION: Distance between the nodule and pleura and SUVmax are independent predictors of VPI in SSN stage I lung adenocarcinoma. Further, combining these factors improves their predictive ability.

Gefitinib with or without Transarterial Infusion Chemotherapy (Cisplatin) for Large Nonsmall Cell Lung Cancer with Epidermal Growth Factor Receptor Mutations.

PURPOSE: To retrospectively investigate the safety and benefit of gefitinib plus transarterial infusion (TAI) therapy as a first-line treatment compared to gefitinib alone for patients with large (>7 cm) nonsmall cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. MATERIALS AND METHODS: Between January 2010 and December 2013, 92 consecutive treatment-naïve patients with large NSCLC with EGFR mutations, who were treated using gefitinib plus TAI (G+T, n = 42) or gefitinib alone (G, n = 50) were reviewed. The primary endpoints were the objective response rate (ORR) and tumor reduction rate. The secondary endpoints were progression-free survival (PFS) and overall survival (OS), and safety was also assessed. RESULTS: The baseline characteristics of the 2 groups were balanced, and no patients experienced treatment-related death. Toxicity outcomes did not differ between the G+T and G groups. The tumor reduction rate in the G+T group was significantly higher than that in the G group (42.9 vs 31.9%, P = .028). The ORR was 83% in the G+T group and 72% in the G group (P = .197). The median PFS was significantly longer in the G+T group than in the G group (14.0 vs 10.0 months, P = .023). The median OS was 30.0 months in the G+T group and 27.0 months in the G group (P = .235). CONCLUSIONS: This study suggests that compared with gefitinib alone, combination therapy with gefitinib plus TAI was well tolerated and potentially improved the tumor reduction rate and PFS in patients with large NSCLC with EGFR mutations.