Local ablation or radioembolization of colorectal cancer metastases: comorbidities or older age do not affect overall survival

Background: Local ablative techniques are emerging in patients with oligometastatic disease from colorectal carcinoma, commonly described as less invasive than surgical methods. This single arm cohort seeks to determine whether such methods are suitable in patients with comorbidities or higher age. Methods: Two hundred sixty-six patients received radiofrequency ablation (RFA), CT-guided high-dose rate brachytherapy (HDR-BT) or Y90-radioembolization (Y90-RE) during treatment of metastatic colorectal cancer (mCRC). This cohort comprised of patients with heterogenous disease stages from single liver lesions to multiple organ systems involvement commonly following multiple chemotherapy lines. Data was reviewed retrospectively for patient demographics, previous therapies, initial or disease stages at first intervention, comorbidities and mortality. Comorbidity was measured using the Charlson Comorbidity Index (CCI) and age-adjusted Charlson Index (CACI) excluding mCRC as the index disease. Kaplan-Meier survival analysis and Cox regression were used for statistical analysis. Results: Overall median survival of 266 patients was 14 months. Age >= 70 years did not influence survival after local therapies. Similarly, CCI or CACI did not affect the patients prognoses in multivariate analyses. Moderate or severe renal insufficiency (n = 12;p = 0.005) was the only single comorbidity identified to negatively affect the outcome after local therapy. Conclusion: Interventional procedures for mCRC may be performed safely even in elderly and comorbid patients. In severe renal insufficiency, the use of invasive techniques should be limited to selected cases

Extensive Use of Interventional Therapies Improves Survival in Unresectable or Recurrent Intrahepatic Cholangiocarcinoma

Aim. To assess the outcomes of patients with unresectable intrahepatic cholangiocellular carcinoma (ICC) treated by a tailored therapeutic approach, combining systemic with advanced image-guided local or locoregional therapies. Materials and Methods. Treatment followed an algorithm established by a multidisciplinary GI-tumor team. Treatment options comprised ablation (RFA, CT-guided brachytherapy) or locoregional techniques (TACE, radioembolization, i.a. chemotherapy). Results. Median survival was 33.1 months from time of diagnosis and 16.0 months from first therapy. UICC stage analysis showed a median survival of 15.9 months for stage I, 9 months for IIIa, 18.4 months for IIIc, and 13 months for IV. Only the number of lesions, baseline serum CEA and serum CA19-9, and objective response (RECIST) were independently associated with survival. Extrahepatic metastases had no influence. Conclusion. Patients with unresectable ICC may benefit from hepatic tumor control provided by local or locoregional therapies. Future prospective study formats should focus on supplementing systemic therapy by classes of interventions (“toolbox”) rather than specific techniques, that is, local ablation leading to complete tumor destruction (such as RFA) or locoregional treatment leading to partial remission (such as radioembolization). This trial is registered with German Clinical Trials Registry (Deutsche Register Klinischer Studien), DRKS-ID: DRKS00006237

Modified transarterial chemoembolization with locoregional administration of sorafenib for treating hepatocellular carcinoma: feasibility, efficacy, and safety in the VX-2 rabbit liver tumor model

PURPOSE:We aimed to assess the feasibility, efficacy and safety of a local application of sorafenib within a conventional transarterial chemoembolization in the VX-2 tumor-bearing rabbit model.METHODS:VX-2 tumors were induced in the left liver lobe of 10 New Zealand White rabbits. After two weeks, growth was verified by contrast-enhanced computed tomography (CT). Five rabbits were treated by transarterial chemoembolization using an emulsion of sorafenib and ethiodized oil (referred to as SORATACE; n=5). Rabbits receiving oral sorafenib for two weeks (n=2) and untreated rabbits (n=3) served as controls. After two weeks, contrast-enhanced CT was performed, followed by animal necropsy.RESULTS:The change in tumor diameter between baseline and follow-up was significantly different in the SORATACE group compared with the other groups; tumor shrinkage was observed in the SORATACE group only (P = 0.016). In both control groups, preserved hypervascularity was seen in the follow-up CT in all but one tumor. All tumors in the SORATACE group were devascularized in the follow-up CT. Importantly, substantial parenchymal damage in nontargeted areas of the tumor-bearing liver lobe was seen in rabbits treated with SORATACE.CONCLUSION:SORATACE demonstrated high efficacy in the treatment of experimental VX-2 liver tumors but was also associated with substantial liver parenchymal toxicity

Correlation of liver enhancement in gadoxetic acid-enhanced MRI with liver functions: a multicenter-multivendor analysis of hepatocellular carcinoma patients from SORAMIC trial

OBJECTIVES To evaluate the correlation between liver enhancement on hepatobiliary phase and liver function parameters in a multicenter, multivendor study. METHODS A total of 359 patients who underwent gadoxetic acid-enhanced MRI using a standardized protocol with various scanners within a prospective multicenter phase II trial (SORAMIC) were evaluated. The correlation between liver enhancement on hepatobiliary phase normalized to the spleen (liver-to-spleen ratio, LSR) and biochemical laboratory parameters, clinical findings related to liver functions, liver function grading systems (Child-Pugh and Albumin-Bilirubin ALBI), and scanner characteristics were analyzed using uni- and multivariate analyses. RESULTS There was a significant positive correlation between LSR and albumin (rho = 0.193; p < 0.001), platelet counts (rho = 0.148; p = 0.004), and sodium (rho = 0.161; p = 0.002); and a negative correlation between LSR and total bilirubin (rho = -0.215; p < 0.001) and AST (rho = -0.191; p < 0.001). Multivariate analysis confirmed independent significance for each of albumin (p = 0.022), total bilirubin (p = 0.045), AST (p = 0.031), platelet counts (p = 0.012), and sodium (p = 0.006). The presence of ascites (1.47 vs. 1.69, p < 0.001) and varices (1.55 vs. 1.69, p = 0.006) was related to significantly lower LSR. Similarly, patients with ALBI grade 1 had significantly higher LSR than patients with grade 2 (1.74 ± 0.447 vs. 1.56 ± 0.408, p < 0.001); and Child-Pugh A patients had a significantly higher LSR than Child-Pugh B (1.67 ± 0.44 vs. 1.49 ± 0.33, p = 0.021). Also, LSR was negatively correlated with MELD-Na scores (rho = -0.137; p = 0.013). However, one scanner brand was significantly associated with lower LSR (p < 0.001). CONCLUSIONS The liver enhancement on the hepatobiliary phase of gadoxetic acid-enhanced MRI is correlated with biomarkers of liver functions in a multicenter cohort. However, this correlation shows variations between scanner brands. KEY POINTS • The correlation between liver enhancement on the hepatobiliary phase of gadoxetic acid-enhanced MRI and liver function is consistent in a multicenter-multivendor cohort. • Signal intensity-based indices (liver-to-spleen ratio) can be used as an imaging biomarker of liver function. • However, absolute values might change between vendors

Quantitative in vivo assessment of radiation injury of the liver using Gd-EOB-DTPA enhanced MRI: tolerance dose of small liver volumes

<p>Abstract</p> <p>Backround</p> <p>Hepatic radiation toxicity restricts irradiation of liver malignancies. Better knowledge of hepatic tolerance dose is favourable to gain higher safety and to optimize radiation regimes in radiotherapy of the liver. In this study we sought to determine the hepatic tolerance dose to small volume single fraction high dose rate irradiation.</p> <p>Materials and methods</p> <p>23 liver metastases were treated by CT-guided interstitial brachytherapy. MRI was performed 3 days, 6, 12 and 24 weeks after therapy. MR-sequences were conducted with T1-w GRE enhanced by hepatocyte-targeted Gd-EOB-DTPA. All MRI data sets were merged with 3D-dosimetry data. The reviewer indicated the border of hypointensity on T1-w images (loss of hepatocyte function) or hyperintensity on T2-w images (edema). Based on the volume data, a dose-volume-histogram was calculated. We estimated the threshold dose for edema or function loss as the D₉₀, i.e. the dose achieved in at least 90% of the pseudolesion volume.</p> <p>Results</p> <p>At six weeks post brachytherapy, the hepatocyte function loss reached its maximum extending to the former 9.4Gy isosurface in median (i.e., ≥9.4Gy dose exposure led to hepatocyte dysfunction). After 12 and 24 weeks, the dysfunctional volume had decreased significantly to a median of 11.4Gy and 14Gy isosurface, respectively, as a result of repair mechanisms. Development of edema was maximal at six weeks post brachytherapy (9.2Gy isosurface in median), and regeneration led to a decrease of the isosurface to a median of 11.3Gy between 6 and 12 weeks. The dose exposure leading to hepatocyte dysfunction was not significantly different from the dose provoking edema.</p> <p>Conclusion</p> <p>Hepatic injury peaked 6 weeks after small volume irradiation. Ongoing repair was observed up to 6 months. Individual dose sensitivity may differ as demonstrated by a relatively high standard deviation of threshold values in our own as well as all other published data.</p

Radiobiological restrictions and tolerance doses of repeated single-fraction hdr-irradiation of intersecting small liver volumes for recurrent hepatic metastases

<p>Abstract</p> <p>Background</p> <p>To assess radiobiological restrictions and tolerance doses as well as other toxic effects derived from repeated applications of single-fraction high dose rate irradiation of small liver volumes in clinical practice.</p> <p>Methods</p> <p>Twenty patients with liver metastases were treated repeatedly (2 - 4 times) at identical or intersecting locations by CT-guided interstitial brachytherapy with varying time intervals. Magnetic resonance imaging using the hepatocyte selective contrast media Gd-BOPTA was performed before and after treatment to determine the volume of hepatocyte function loss (called pseudolesion), and the last acquired MRI data set was merged with the dose distributions of all administered brachytherapies. We calculated the BED (biologically equivalent dose for a single dose d = 2 Gy) for different α/β values (2, 3, 10, 20, 100) based on the linear-quadratic model and estimated the tolerance dose for liver parenchyma D₉₀as the BED exposing 90% of the pseudolesion in MRI.</p> <p>Results</p> <p>The tolerance doses D₉₀after repeated brachytherapy sessions were found between 22 - 24 Gy and proved only slightly dependent on α/β in the clinically relevant range of α/β = 2 - 10 Gy. Variance analysis showed a significant dependency of D₉₀with respect to the intervals between the first irradiation and the MRI control (p < 0.05), and to the number of interventions. In addition, we observed a significant inverse correlation (p = 0.037) between D₉₀and the pseudolesion's volume. No symptoms of liver dysfunction or other toxic effects such as abscess formation occurred during the follow-up time, neither acute nor on the long-term.</p> <p>Conclusions</p> <p>Inactivation of liver parenchyma occurs at a BED of approx. 22 - 24 Gy corresponding to a single dose of ~10 Gy (α/β ~ 5 Gy). This tolerance dose is consistent with the large potential to treat oligotopic and/or recurrent liver metastases by CT-guided HDR brachytherapy without radiation-induced liver disease (RILD). Repeated small volume irradiation may be applied safely within the limits of this study.</p

Role of diffusion-weighted imaging in response prediction and evaluation after high dose rate brachytherapy in patients with colorectal liver metastases

The aim of the study was to assess the role of diffusion-weighted imaging (DWI) to evaluate treatment response in patients with liver metastases of colorectal cancer