Effect of stereotactic body radiotherapy on regional metabolic liver function investigated in patients by dynamic [18F]FDGal PET/CT.

PURPOSE: Stereotactic body radiotherapy (SBRT) is increasingly used for treatment of liver tumors but the effect on metabolic liver function in surrounding tissue is largely unknown. Using 2-deoxy-2-[18F]fluoro-D-galactose ([18F]FDGal) positron emission tomography (PET)/computed tomography (CT), we aimed to determine a dose-response relationship between radiation dose and metabolic liver function as well as recovery. PROCEDURES: One male subject with intrahepatic cholangiocarcinoma and five subjects (1 female, 4 male) with liver metastases from colorectal cancer (mCRC) underwent [18F]FDGal PET/CT before SBRT and after 1 and 3 months. The dose response was calculated using the data after 1 month and the relative recovery was evaluated after 3 months. All patients had normal liver function at time of inclusion. RESULTS: A linear dose-response relationship for the individual liver voxel dose was seen until approximately 30 Gy. By fitting a polynomial curve to data, a mean TD50 of 18 Gy was determined with a 95% CI from 12 to 26 Gy. After 3 months, a substantial recovery was observed except in tissue receiving more than 25 Gy. CONCLUSIONS: [18F]FDGal PET/CT makes it possible to determine a dose-response relationship between radiation dose and metabolic liver function, here with a TD50 of 18 Gy (95% CI 12-26 Gy). Moreover, the method makes it possible to estimate metabolic recovery in liver tissue.

Intensified Induction Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Anus-A Population-Based Experience from the Danish Anal Cancer Group.

Locally advanced squamous cell carcinoma of the anus (LASCCA) has a poor prognosis with a high risk of treatment failure calling for intensified therapy. We present the long-term follow-up of a nationwide cohort of LASCCA treated with intensified induction chemotherapy (ICT). The study included patients with LASCCA (T3-4N0 or T1-4N+) treated with at least one cycle of ICT (cisplatin, ifosfamide, leucoverin, and 5-flourouracil) between 1998-2018. Data were retrospectively collected from medical records, and statistics were performed in STATA 16.1. In total, 166 patients with LASCCA were identified. Following ICT, 157 patients (95%) received primary curative treatment with either radiotherapy (70%), chemoradiotherapy (27%), or abdominal perineal resection (3%). The overall local tumor response rate after ICT was 76% with 20 (13%) achieving complete local tumor response. After the primary treatment, 123 patients (79%) obtained complete response, and 27 underwent salvage surgery due to persistent disease. The median follow-up time was 6 years, local and distant failure rates 22% and 13%, respectively. The 3- and 5-year disease-free survival rates were 70% and 67%, and the 3- and 5-year overall survival rates were 76% and 70%, respectively. Intensified ICT regimen could be a supplementary treatment option in the most advanced cases of LASCCA. Prospective randomized trials are needed to investigate this approach further.

A phase I study on stereotactic body radiotherapy of liver metastases based on functional treatment planning using positron emission tomography with 2-[18F]fluoro-2-deoxy-d-galactose.

BACKGROUND AND PURPOSE: The galactose analog 2-[18F]fluoro-2-deoxy-d-galactose (FDGal) is used for quantification of regional hepatic metabolic capacity by functional positron emission tomography computerized tomography (PET/CT). In the present study, FDGal PET/CT was used for functional treatment planning (FTP) of stereotactic body radiotherapy (SBRT) of liver metastases with the aim of minimizing radiation dose to the best functioning liver tissue. MATERIAL AND METHODS: Fourteen patients referred for SBRT had FDGal PET/CT performed before and one month after the treatment. The planning CT and the FDGal PET/CT images were deformable co-registered. RESULTS: A reduction in the mean dose of approximately 2 Gy to the best functioning sub-volumes was obtained. One patient developed grade 2 acute morbidity and no patients experienced grade 3 or higher acute morbidities. The regional hepatic metabolic function post-treatment was linearly correlated to the regional radiation dose and for each 10-Gy increase in dose (γ10Gy), the metabolic function was reduced by 12%. A 50% reduction was seen at 22.9 Gy in 3 fractions (CI 95%: 16.7-30.4 Gy). CONCLUSION: The clinical study demonstrates the feasibility for FTP in patients with liver metastases and it was possible to minimize the radiation dose to the best functioning liver tissue.

Metabolic liver function after stereotactic body radiation therapy for hepatocellular carcinoma.

Purpose The time course of changes of the liver function after stereotactic body radiotherapy (SBRT) was analyzed in patients treated for non-resectable hepatocellular carcinoma (HCC). Patients and methods Twenty-six patients with non-resectable HCC treated with SBRT were included in this study. Clinical, biochemical and treatment-related parameters were retrospectively collected. S-albumin, s-bilirubin, s-alkaline phosphatase (AP) and s-alanine transaminase (ALAT) at 0, 3, 6, and 12 months after radiotherapy were analyzed. Results Seventeen and nine patients were Child-Pugh class A and B, respectively. The liver was exposed to relatively high radiation doses with mean doses of 1.9-26 Gy. None of the patients developed classic radiotherapy-induced liver disease (RILD), but two patients developed non-classic RILD. Two patients developed grade 3 ascites and no grade 4-5 toxicities were observed. Six patients declined in Child-Pugh class. The s-albumin decreased significantly from a pretreatment median of 37.4-34.36 g/l at three months after SBRT and stabilized thereafter. S-bilirubin, s-AP and s-ALAT did not change significantly over the study period. Conclusion Despite the fact that patients received high radiation dose to the liver, there was only moderate morbidity related to the treatment. The s-albumin decreases over three months after SBRT reflecting minor to moderate hepatic toxicity. S-albumin should be observed in the follow-up of HCC patients treated with SBRT.

Survival and prognostic factors in 321 patients treated with stereotactic body radiotherapy for oligo-metastases.

BACKGROUND AND PURPOSE: To establish a model to predict survival after SBRT for oligo-metastases in patients considered ineligible for surgical resection (SR) and radiofrequency ablation (RFA). MATERIAL AND METHODS: Overall survival (OS) rates were estimated in 321 patients treated for 587 metastases with SBRT over 13years. Patients were treated for a variety of metastasis types with colorectal cancer (CRC) being the most frequent (n=201). RESULTS: With a median follow-up time of 5.0years, the median OS was 2.4years (95% CI 2.3-2.7) and the survival rates were 80%, 39%, 23% and 12% at 1, 3, 5 and 7.5years after SBRT, respectively. WHO performance status (PS) (0-1) (HR 0.49; p<0.001), solitary metastasis (HR 0.75; p=0.049), metastasis ⩽30mm (HR 0.53; p<0.001), metachronous metastases (HR 0.71; p=0.02) and pre-SBRT chemotherapy (HR 0.59; p<0.001) were independently related to favorable OS. Median OS rates were 7.5, 2.8, 2.5, 1.7 and 0.8years with 0, 1, 2, 3, ⩾4 unfavorable prognostic factors, respectively. The treatment-related morbidity was moderate. However, three deaths were possibly treatment-related. CONCLUSION: Prognostic factors may predict long-term survival in patients with oligo-metastases treated with SBRT.