Dose escalation in radiotherapy for incomplete transarterial chemoembolization of hepatocellular carcinoma.

PURPOSE: To investigate the efficacy of radiation dose escalation in patients with hepatocellular carcinoma (HCC) after incomplete transarterial chemoembolization (TACE). METHODS: This study evaluated retrospective data of 323 HCC patients who received radiotherapy after incomplete TACE from 2001-2016. Radiation dose in biologically effective dose (BED) (α/ß = 10) was categorized as <72 Gy (261 patients) and ≥72 Gy (62 patients). Simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) was used significantly more frequently in the high-dose group (64.5% vs. 12.9%; P < 0.001). Local failure-free rate (LFFR), progression-free rate (PFR), and toxicities were compared between the two groups. Additionally, propensity score matching was performed. RESULTS: Median follow-up time for patients who were alive at the time of analysis was 47 months (range 18-189 months). Median overall survival after radiotherapy was 14 months. In multivariate analysis, BED ≥72 Gy was an independent predictor of favorable LFFR (hazard ratio [HR] 0.32; 95% confidence interval [CI] 0.14-0.72; P = 0.006) and PFR (HR 0.67; 95% CI 0.45-0.98; P = 0.04). In the propensity score-matched cohort (62 pairs), 1­year LFFR (94% vs. 81%; P = 0.002), and 1­year PFR (49% vs. 42%; P = 0.01) were significantly higher in the high-dose group. Treatment-related toxicities were comparable between the high-dose and low-dose groups (classic radiation-induced liver disease: 5.3% [3/57] vs. 13.8% [29/210], P = 0.08; grade 2-4 gastrointestinal bleeding: 3.2% [2/62] vs. 7.3% [19/261], P = 0.39). CONCLUSION: Radiation dose with BED ≥72 Gy improved LFFR and PFR without increasing toxicity. In radiotherapy for incomplete TACE of HCC, dose escalation using SIB-IMRT should be actively considered to improve oncologic outcome.

A prospective Phase II study for the efficacy of radiotherapy in combination with zoledronic acid in treating painful bone metastases from gastrointestinal cancers.

We investigated the efficacy of combined radiotherapy (RT) and zoledronic acid in treating painful bone metastases from gastrointestinal cancers. Sixty patients were prospectively enrolled between November 2014 and July 2016. The most common primary cancer type was hepatocellular carcinoma (HCC, n = 25), followed by colorectal cancer (n = 6). Patients received external beam RT of 30-54 Gy in 10-17 fractions or 20 Gy in 5 fractions for symptomatic bone metastases. On the first day of RT, patients received 4 mg intravenous zoledronic acid, which was repeated monthly for a total of six cycles. The mean pain score before treatment was 6.7, and it decreased to 2.8 at 1 month and 2.1 at 3 months (P < 0.001).The overall pain response rates at 1 and 3 months were 95% and 96%, respectively. Among the 24 patients who underwent magnetic resonance imaging, 71% were responders, with a complete response in 1 patient and partial in 16 patients. Combined treatment significantly decreased levels of macrophage inflammatory protein-1α and matrix metalloproteinase (MMP)-2 and -3 compared with baseline (all P < 0.05). In HCC patients, IL-6 and MMP-9 levels were significantly lower 1 month after treatment (P < 0.05). The mean quality of life (QOL) score improved from 66 to 56 at 1 month (P < 0.001) and 55 at 3 months (P = 0.016). The median survival was 7 months. In conclusion, RT with zoledronic acid decreased bone pain and improved QOL in patients with painful bone metastases from gastrointestinal cancers. Radiographic findings and serum biomarker measurements were closely correlated with therapeutic responses.

Dose escalation by intensity modulated radiotherapy in liver-directed concurrent chemoradiotherapy for locally advanced BCLC stage C hepatocellular carcinoma.

PURPOSE: To evaluate the effects of dose escalation by intensity-modulated radiotherapy (IMRT) in liver-directed concurrent chemoradiotherapy for locally advanced Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma (BCLC-C HCC). MATERIALS AND METHODS: During 2005-2016, 637 patients with BCLC-C HCC received RT with concurrent hepatic arterial 5-fluorouracil. Patients were divided into two groups according to the biologically effective doses for a tumor (α/ß = 10 Gy): <72 Gy (536 patients) and ≥72 Gy (101 patients). In each group, 128/536 (24%) and 94/101 patients (93%) used IMRT, respectively. RESULTS: The median follow-up for patients alive at the time of analysis was 36 months (range, 6-159 months). For ≥72 Gy and <72 Gy groups, the median overall survival (OS) was 21 and 13 months, respectively (P = .002). The 1-year local failure-free survival (LFFS) were significantly higher in high-dose group (95% vs. 79%; P < .001). After propensity score matching, high-dose group still had significantly better 1-year OS (62% vs. 51%; P = .03) and 1-year LFFS (95% vs. 78%; P = .008). In the multivariate model, RT dose was an independent predictor of LFFS and OS. The surgical conversion rate was significantly higher in high-dose group (20% vs. 12%, P = .03), with substantially increased median OS among patients who underwent surgery (104 months vs. 11 months; P < .001). There were no significant differences in gastrointestinal bleeding or radiation-induced liver disease. CONCLUSIONS: In liver-directed concurrent chemoradiotherapy, radiation dose escalation by IMRT increased LFFS and OS for locally advanced BCLC-C HCC. It also increased the conversion rate to curative resection, which was attributable to increased OS.