Radiation-induced liver disease (RILD), often called radiation hepatitis, is a syndrome characterized by the development of anicteric ascites approximately 2 weeks to 4 months after hepatic irradiation. There has been a renewed interest in hepatic irradiation because of two significant advances in cancer treatment: three dimensional radiation therapy treatment planning and bone marrow transplantation using total body irradiation. RILD resulting from liver radiation can usually be distinguished clinically from that resulting from the preparative regime associated with bone marrow transplantation. However, both syndromes demonstrate the same pathological lesion: veno-occlusive disease. Recent evidence suggests that elevated transforming growth factor beta levels may play a role in the development of veno-occlusive disease. Three dimensional treatment planning offers the potential to determine the radiation dose and volume dependence of RILD, permitting the safe delivery of high doses of radiation to parts of the liver. The chief therapy for RILD is diuretics, although some advocate steroids for severe cases. The characteristics of RILD permit the development of a grading system modeled after the NCI Acute Common Toxicity Criteria, which incorporates standard criteria of hepatic dysfunction.
"The role of radiation in the induction of fibrosis has been well documented. Following radiotherapy to treat cancer, patients may develop fibrosis in different organs, such as lung (Ghafoori et al. 2008; Williams et al. 2010), heart (Finch et al. 2014), liver (Lawrence et al. 1995), gastrointestinal (GI) tract (Stacey and Green 2014), and skin (Bourgeois et al. 2003). Additionally, excessive cutaneous fibrosis was observed in survivors of the Chernobyl power plant disaster 5–9 y after the accident (Peter et al. 1999). "
[Show abstract][Hide abstract] ABSTRACT: Exposure to sufficiently high doses of ionizing radiation is known to cause fibrosis in many different organs and tissues. Connective tissue growth factor (CTGF/CCN2), a member of the CCN family of matricellular proteins, plays an important role in the development of fibrosis in multiple organs. The aim of the present study was to quantify the gene and protein expression of CTGF in a variety of organs from non-human primates (NHP) that were previously exposed to potentially lethal doses of radiation. Tissues from non-irradiated NHP and NHP exposed to whole thoracic lung irradiation (WTLI) or partial-body irradiation with 5% bone marrow sparing (PBI/BM5) were examined by real-time quantitative reverse transcription PCR, western blot, and immunohistochemistry. Expression of CTGF was elevated in the lung tissues of NHP exposed to WTLI relative to the lung tissues of the non-irradiated NHP. Increased expression of CTGF was also observed in multiple organs from NHP exposed to PBI/BM5 compared to non-irradiated NHP; these included the lung, kidney, spleen, thymus, and liver. These irradiated organs also exhibited histological evidence of increased collagen deposition compared to the control tissues. There was significant correlation of CTGF expression with collagen deposition in the lung and spleen of NHP exposed to PBI/BM5. Significant correlations were observed between spleen and multiple organs on CTGF expression and collagen deposition, respectively, suggesting possible crosstalk between spleen and other organs. These data suggest that CTGF levels are increased in multiple organs after radiation exposure and that inflammatory cell infiltration may contribute to the elevated levels of CTGF in multiple organs.
Health physics 10/2015; 109(5):374-390. DOI:10.1097/HP.0000000000000343 · 1.27 Impact Factor
"Historically, the radiation therapy has had a limited role in the treatment of liver cancer due to the low tolerance of the liver to radiation dose and it was difficult to deliver the radiation doses necessary to ablate gross tumors without causing radiation-induced liver disease (RILD) . However, technical developments of radiation therapy such as three-dimensional conformal radiotherapy (3D-CRT) and intensity modulated radiation therapy have gradually expanded their role from a palliative to a curative intent, whereby high-dose radiation can be delivered to the tumor more safely without affecting the liver function. "
[Show abstract][Hide abstract] ABSTRACT: Liver metastasis in solid tumors, including colorectal cancer, is the most frequent and lethal complication. The development of systemic therapy has led to prolonged survival. However, in selected patients with a finite number of discrete lesions in liver, defined as oligometastatic state, additional local therapies such as surgical resection, radiofrequency ablation, cryotherapy, and radiotherapy can lead to permanent local disease control and improve survival. Among these, an advance in radiation therapy made it possible to deliver high dose radiation to the tumor more accurately, without impairing the liver function. In recent years, the introduction of stereotactic ablative radiotherapy (SABR) has offered even more intensive tumor dose escalation in a few fractions with reduced dose to the adjacent normal liver. Many studies have shown that SABR for oligometastases is effective and safe, with local control rates widely ranging from 50% to 100% at one or two years. And actuarial survival at one and two years has been reported ranging from 72% to 94% and from 30% to 62%, respectively, without severe toxicities. In this paper, we described the definition and technical aspects of SABR, clinical outcomes including efficacy and toxicity, and related parameters after SABR in liver oligometastases from colorectal cancer.
BioMed Research International 04/2014; 2014:340478. DOI:10.1155/2014/340478 · 3.17 Impact Factor
"Radiation-induced liver disease (RILD) is a traditionally accepted concept of hepatic toxicity. Classic RILD is a subacute hepatic toxicity that presents with anicteric ascites, hepatomegaly, and elevated alkaline phosphatase levels; it typically occurs between 4 and 8 weeks after the completion of RT
[5,22]. Previously, classic RILD was a serious problem that could occur in response to radiation amounts of 30–35 Gy to the whole liver; however, the incidence decreased after partial volume irradiation became more frequently used
[Show abstract][Hide abstract] ABSTRACT: We attempted to analyze the effects of an increase in the Child-Pugh (CP) score on the overall survival of patients with unresectable hepatocellular carcinoma (HCC) after radiotherapy (RT).
From March 2006 to February 2012, 103 patients received RT using the TomoTherapy Hi-Art at Incheon St. Mary's Hospital and Seoul St. Mary's Hospital. The dose per fraction was 1.8-5 Gy, and the total dose was 40-60 Gy (median, 50 Gy). We considered an increase of at least 2 points in the CP score within 3 months after RT to be clinically important radiation-induced hepatic toxicity and analyzed the effects of an increased CP score on overall survival.
The median follow-up duration was 11.6 months (range, 3.5-85.3 months). The median survival time was 11.6 months. In multivariate analysis, planning target volume and an increase in the CP score after RT were found to be a statistically significant factors (p = 0.010 and 0.015, respectively). In a comparison of cases with and without an increase in the CP score, there was an 11.0-month difference in the median survival time (6.9 vs. 17.9 months), and the relative risk of mortality was 1.8.
An increase of at least 2 points in the CP score within 3 months of RT completion is an important on-treatment factor that affects overall survival. To minimize such increases, careful patient selection and a more sophisticated radiation treatment plan are imperative.
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