E. Osmundson

Predicting Radiotherapy Responses and Treatment Outcomes Through Analysis of Circulating Tumor DNA

Tumors continually shed DNA into the blood where it can be detected as circulating tumor DNA (ctDNA). Although this phenomenon has been recognized for decades, techniques that are sensitive and specific enough to robustly detect ctDNA have only become available recently. Quantification of ctDNA represents a new approach for cancer detection and disease burden quantification that has the potential to revolutionize response assessment and personalized treatment in radiation oncology. Analysis of ctDNA has many potential applications, including detection of minimal residual disease following radiotherapy, noninvasive tumor genotyping, and early detection of tumor recurrence. Ultimately, ctDNA-based assays could lead to personalization of therapy based on identification of somatic alterations present in tumors and changes in ctDNA concentrations before and after treatment. In this review, we discuss methods of ctDNA detection and clinical applications of ctDNA-based biomarkers in radiation oncology, with a focus on recently developed techniques that use next-generation sequencing for ctDNA quantification.

Central liver toxicity after SBRT: An expanded analysis and predictive nomogram

PURPOSE To further explore the correlation of central biliary tract (cHBT) radiation doses with hepatobiliary toxicity (HBT) after stereotactic body radiation therapy (SBRT) in a larger patient dataset. METHODS We reviewed the treatment and outcomes of all patients who received SBRT for primary liver cancer (PLC) and metastatic liver tumors between July 2004 and November 2015 at our institution. The cHBT was defined as isotropic expansions (5, 10, 15, 20 and 25mm) from the portal vein (PV). Doses were converted to biologically effective doses by using the standard linear quadratic model with α/β of 10 (BED10). HBT was graded according to the Common Terminology Criteria for Adverse Events v4.03. RESULTS Median follow-up was 13months. Out of the 130 patients with complete follow-up records analyzed, 60 (46.1%) had liver metastases, 40 (30.8%) had hepatocellular carcinoma (HCC), 26 (20%) had cholangiocarcinoma (CCA) and 4 (3.1%) patients other PLC histologies. Thirty-three (25.4%) grade 2+ and 28 (21.5%) grade 3+ HBT were observed. Grade 3+ HBT was seen in 13 patients (50%) with CCA, 7 patients (17.5%) with HCC and 7 (11.7%) patients with liver metastases. SBRT doses to the cHBT were highly associated with HBT, but only for PLC patients when analyzed by histological subtype. The 15mm expansion from the PV (cHBT15) proved to be an appropriate surrogate for the cHBT. The strongest cHBT15 dose predictors for G3+ HBT for PLC were the VBED1040⩾37cc (p<0.0001) and the VBED1030⩾45cc (p<0.0001). CONCLUSION SBRT doses to the cHBT are associated with occurrence of HBT only in PLC patients. Limiting the dose to the cHBT to VBED1040<37cc and VBED1030<45cc when treating PLC patients with SBRT may reduce the risk of HBT.

Assessment of hepatic function decline after stereotactic body radiation therapy for primary liver cancer

PURPOSE This study aims to determine how the albumin-bilirubin (ALBI) score compares with the Child-Pugh (CP) score for assessing liver function following stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS In total, 60 patients, 40 with hepatocellular carcinoma (HCC) and 20 with cholangiocarcinoma (CCA), were treated with SBRT. Liver function panels were obtained before and at 1, 3, 6, and 12 months after SBRT. Laboratory values were censored after locoregional recurrence, further liver-directed therapies, or liver transplant. RESULTS A significant decline in hepatic function occurred after SBRT for HCC patients only (P = .001 by ALBI score; P < .0001 by CP score). By converting radiation doses to biologically equivalent doses by using a standard linear quadratic model using α/β of 10, the strongest dosimetric predictor of liver function decline for HCC was the volume of normal liver irradiated by a dose of 40 Gy when assessing liver function by the ALBI score (P = .07), and the volume of normal liver irradiated by a dose of 20 Gy by using the CP score (P= .0009). For CCA patients, the volume of normal liver irradiated by a dose of 40 Gy remained the strongest dosimetric predictor when using the ALBI score (P = .002), but no dosimetric predictor was significant using the CP score. Hepatic function decline correlated with worse overall survival for HCC (by ALBI, P = .0005; by CP, P < .0001) and for CCA (by ALBI, P = NS; by CP, P = .008). CONCLUSIONS ALBI score was similarly able to predict hepatic function decline compared with CP score, and both systems correlated with survival.

Stereotactic body radiation therapy and central liver toxicity: A case report

Stereotactic body radiation therapy (SBRT) has become an increasingly common component in the treatment of primary andmetastatic liver tumors. Liver SBRT allows for focused high-dose radiation to the target while minimizing dose to the remaining liver. In the majority of cases, this treatment is effective and well tolerated; however, some studies have reported up to 30% grade 3 or higher toxicity.1 One of the potential risks of liver SBRT is radiation-induced liver disease (RILD), which is characterized by nonicteric ascites, hepatomegaly, and elevated alkaline phosphatase and typically develops 4 weeks to 3 months after treatment. The risk of RILD can be reduced by minimizing the mean liver dose or by sparing a critical volume of liver from receiving more than the dose tolerance. However, for centrally located liver lesions, RILD does not account for damage specific to the central hepatobiliary tree and portal vein, and the traditional dose constraints do not account for the specific tolerance of these structures. Toxicity of the central hepatobiliary tree may be attributable to stenosis/stricture, which could lead to elevated alkaline phosphatase, jaundice, and cholangitis. To further characterize the potential toxicity of SBRT, we describe a case of a patient who underwent liver