Purpose
To explore the potential correlation between baseline interleukin (IL) values and overall survival or objective response in patients with hepatocellular carcinoma (HCC) receiving sorafenib.
...Methods
A subset of patients with HCC undergoing sorafenib monotherapy within a prospective multicenter phase II trial (SORAMIC, sorafenib treatment alone vs. combined with Y90 radioembolization) underwent baseline IL-6 and IL-8 assessment before treatment initiation. In this exploratory post hoc analysis, the best cut-off points for baseline IL-6 and IL-8 values predicting overall survival (OS) were evaluated, as well as correlation with the objective response.
Results
Forty-seven patients (43 male) with a median OS of 13.8 months were analyzed. Cut-off values of 8.58 and 57.9 pg/mL most effectively predicted overall survival for IL-6 and IL-8, respectively. Patients with high IL-6 (HR, 4.1 1.9–8.9,
p
< 0.001) and IL-8 (HR, 2.4 1.2–4.7,
p
= 0.009) had significantly shorter overall survival than patients with low IL values. Multivariate analysis confirmed IL-6 (HR, 2.99 1.22–7.3,
p
= 0.017) and IL-8 (HR, 2.19 1.02–4.7,
p
= 0.044) as independent predictors of OS. Baseline IL-6 and IL-8 with respective cut-off values predicted objective response rates according to mRECIST in a subset of 42 patients with follow-up imaging available (IL-6, 46.6% vs. 19.2%,
p
= 0.007; IL-8, 50.0% vs. 17.4%,
p
= 0.011).
Conclusion
IL-6 and IL-8 baseline values predicted outcomes of sorafenib-treated patients in this well-characterized prospective cohort of the SORAMIC trial. We suggest that the respective cut-off values might serve for validation in larger cohorts, potentially offering guidance for improved patient selection.
Image-guided brachytherapy with a single-fraction irradiation (high-dose-rate brachytherapy - HDR-BT) is a promising local ablation technique for unresectable liver metastases. The occurrence of ...needle track seeding after biopsy and microwave ablation (MWA) has been documented primarily in hepatocellular carcinoma (HCC). Comprehensive data on colorectal metastases and treatment with HDR-BT is missing. The aim of this study was to investigate the incidence of extra- and intra-hepatic track seeding after HDR-BT in patients with colorectal metastases of the liver, and the identification of possible risk factors.
Patients with at least one treatment of HDR-BT were included. Two readers identified possible track seeding after at least 3 months of follow-up. For verification, we used image fusion of CT/MRI images from 3D irradiation plan and follow-up. Intra- and extra-hepatic seeding were included. As possible risk factors, demographics, tumor grading, and aspects of catheter placement were identified, and generalized linear mixed model for evaluation was applied.
On total, 138 patients were included in the study (85 males). We treated 472 liver lesions with 1,107 catheter placements. Sixteen needle track lesions were identified with a catheter-based risk of 1.5% and patient-based risk of 10.9% during a median follow-up of 543 days. Extra-hepatic track seeding (patient-based risk of 1.4%) was found in two patients only. Possible risk factors were tumor grading (
= 0.01) and using MRI-guidance (
= 0.02). There was also a correlation with a high number of interventions per patient (
= 0.009) and number of treated lesions (
= 0.04).
Brachytherapy for treatment of colorectal metastases is associated with a similar risk for extra-hepatic track seeding compared to radio-frequency ablation (RFA). Intra-hepatic seeding, which has not been studied extensively before, occurs more often with seeding frequency comparable to biopsy of colorectal metastases. Possible risk factors could be tumor grading and using MRI-guidance.
We aimed to evaluate the safety and effectiveness of image-guided high-dose rate interstitial brachytherapy (iBT) for the treatment of patients with hepatic, lymphatic, and pancreatic metastases ...originating from gastric cancer, an entity rarely surgically treatable with curative intent.
Twelve patients with a cumulative number of 36 metastases (29 liver, 2 pancreatic, 5 lymph node) from histologically proven gastric adenocarcinoma received iBT between 2010 and 2016 and were retrospectively analyzed. Every patient underwent palliative chemotherapy prior to iBT. The iBT procedure employs a temporarily, intratumorally placed iridium-192 source in a single fraction with the goal of tumor cell eradication. Effectiveness was assessed clinically and by radiologic imaging every three months.
Local tumor control was achieved in 32 of all treated metastases (89%). Four lesions showed a local recurrence after 7 months. Lesion sizes varied from 9 to 102 mm with a median of 20 mm. The median progression-free survival was 6.6 months (range, 1.8-46.8 months). The median overall survival was 11.4 months (range, 5-47 months). One patient suffered a major complication following iBT, hepatic hematoma and abscess (Common Terminology Criteria for Adverse Events grade 3), successfully dealt with by transcutaneous drainage.
iBT is an overall safe procedure, which facilitates high rates of local tumor control in treatment of metastatic gastric adenocarcinoma. Compared with surgical metastasectomy, similar overall survival rates could be achieved in our patient collective after iBT application.
Radiography is one of the most widely used imaging techniques in the world. Since its inception, it has continued to evolve, leading to the development of intelligent and automated radiography ...systems that are able to perceive parts of their environment and respond accordingly. However, such systems do not provide a complete view of the examination space and are therefore unable to detect multiple objects and fully ensure the safety of patients, staff and equipment during the execution of the movement. In this paper, we present a system architecture based on ROS (Robot Operating System) to solve these challenges and integrate an autonomous X-ray device. The architecture retrieves point clouds from range sensors placed at specific locations in the examination room. By integrating different subsystems, the architecture merges the data from the different sensors to map the space. It also implements downsampling and clustering methods to identify objects and later distinguish obstacles. A subsystem generates bounding boxes based on the detected obstacles and feeds them to a motion planning framework (MoveIt!) to enable collision avoidance during motion execution. At the same time, a subsystem implements a deep neural network model (PointNet) to classify the detected obstacles. Finally, the developed system architecture provided promising results after being deployed in a Gazebo simulated examination space and on a use case test platform.
To determine local tumor control after CT-guided brachytherapy at various dose levels and the prognostic impact of extensive cytoreduction in colorectal liver metastases.
Seventy-three patients were ...treated on a single-center prospective trial that was initially designed to be randomized to three dose levels of 15 Gy, 20 Gy, or 25 Gy per lesion, delivered in a single fraction. However, because there was a high rate of cross-over of subjects from higher to lower dose levels, this study is better understood as a prospective trial with three dose levels. No upper size limit for the metastases was applied. We assessed time to local progression, progression-free survival, and overall survival.
According to safety constraints cross-over was performed. The final assignment was n = 98, n = 68, and n = 33 in the 15-Gy, 20-Gy, and 25-Gy groups, respectively. Median diameter of the largest tumor lesion in each patient was 5 cm (range, 1-13.5 cm). Estimated mean local recurrence-free survival for all lesions was 34 months (median not reached). The group assigned to 15 Gy after cross-over displayed 34 local recurrences out of 98 lesions; 20 Gy, 15 out of 68 lesions; 25 Gy, 1 out of 33 lesions. The difference between the 25-Gy and the 20-Gy or 15-Gy group was significant (p < 0.05). Repeated local tumor ablations were the most prominent factor for increased survival and dominated additional systemic antitumor treatments.
Local tumor control after CT-guided brachytherapy of colorectal liver metastases demonstrated a strong dose dependency. The role of extensive minimally invasive tumor ablation in metastatic colorectal cancer needs to be further established.
Background
To confirm the prognostic value of previously published baseline interleukin 6 (IL6) and IL8 cutoff values in survival and liver dysfunction in patients with advanced HCC undergoing
90
Y ...radioembolization.
Methods
A total of 83 patients (77 male) represented a subset of HCC patients undergoing
90
Y radioembolization combined with sorafenib as part of the prospective multicenter phase II trial SORAMIC. IL6 and IL8 levels were determined in serum samples collected at baseline. In this post hoc analysis, we sought to confirm the prognostic value of baseline cutoff values of 6.53 pg/mL and 60.8 pg/mL for IL6 and IL8, respectively, in overall survival (OS) or liver dysfunction (grade 2 bilirubin increase) after treatment.
Results
Median OS was 12.0 months. While low baseline albumin and high bilirubin values were associated with high IL6, liver cirrhosis, alcoholic liver disease, and portal vein infiltration were associated with high IL8.
In univariate analysis, high baseline IL6 and IL8 were associated with significantly shorter overall survival (7.8 vs. 19.0 months for IL6 and 8.4 vs. 16.0 months for IL8). In addition to IL values, liver cirrhosis, Child–Pugh grade, baseline albumin (< 36 g/dL), and total bilirubin (≥ 17 µmol/L), and higher mALBI grade (2b &3) values were associated with OS. At multivariate analysis, high baseline IL6 was the only independent prognostic factor for OS (HR 2.35 1.35–4.1, p = 0.002).
Risk factors for liver dysfunction were high baseline IL6, albumin, and total bilirubin, and mALBI grade as found in univariate analysis. High baseline IL6 (HR 2.67 1.21–5.94, p = 0.016) and total bilirubin ≥ 17 µmol/L (HR 3.73 1.72–8.06, p < 0.001) were independently associated with liver dysfunction.
Conclusion
In advanced HCC patients receiving
90
Y radioembolization combined with sorafenib, baseline IL6 values proved to be prognostic, confirming previous findings in patients undergoing
90
Yradioembolization. IL6 might be useful for patient selection or stratification in future trials.
To assess the association of the apparent diffusion coefficient (ADC) of the psoas muscles and psoas muscle index (PMI) with the activity and behaviour of Crohn's disease (CD).
This was a ...retrospective study of 88 CD patients who underwent magnetic resonance enterography. Patients were classified according to the Montreal Classification in uncomplicated (non-stricturing, non-penetrating, B1), and complicated (structuring B2 and penetrating disease B3). At the level of the third lumbar vertebra, the ADC and PMI were estimated. CD activity was analysed using the Magnetic Resonance Index of Activity (MaRIA), and depending on its values patients were categorized as high or low activity. Additionally, the presence of creeping fat (CrF) was used to evaluate activity. ADC and PMI were using Student's
-test.
Our study included 47 males and 41 females (mean age of 38.69 ±14.4 years). The ADC in uncomplicated (B1,
= 45) and complicated disease (B2 + B3,
= 43) were 1.11 ±0.19 and 1.03 ±0.10 (10
*mm
/s), respectively, (
= 0.02). ADC was significantly lower in patients with stricturing disease than in patients without strictures (1.02 ±0.11 and 1.10 ±0.18 10
mm
/s, respectively,
= 0.01). The group with non-penetrating disease showed higher PMI than those with penetrating disease (5.71 ±1.88 vs. 4.42 ±1.55 cm
/m
, respectively,
= 0.10). There was no significant difference in PMI and ADC between patients with low and high MaRIA or positive and negative CrF.
The ADC of the psoas muscles is significantly lower in CD patients with uncomplicated disease, particularly those with stricturing disease. Therefore, ADC can be considered as an imaging biomarker of myopathic changes in CD patients.
Hepatocellular carcinoma (HCC) is a leading cause of cancer death, and medical treatment options are limited. The multikinase inhibitor sorafenib was the first approved drug widely used for systemic ...therapy in advanced HCC. Sorafenib might affect polyunsaturated fatty acids (PUFA)-derived epoxygenated metabolite levels, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of cytochrome-P450 (CYP)-derived epoxide metabolites derived from PUFA, such as omega-6 arachidonic acid (AA) and omega-3 docosahexaenoic acid (DHA), into their corresponding dihydroxy metabolites. Experimental studies with AA-derived epoxyeicosatrienoic acids (EETs) have shown that they can promote tumor growth and metastasis, while DHA-derived 19,20-epoxydocosapentaenoic acid (19,20-EDP) was shown to have anti-tumor activity in mice. In this study, we found a significant increase in EET levels in 43 HCC patients treated with sorafenib and a trend towards increased levels of DHA-derived 19,20-EDP. We demonstrate that the effect of sorafenib on CYP- metabolites led to an increase of 19,20-EDP and its dihydroxy metabolite, whereas DHA plasma levels decreased under sorafenib treatment. These data indicate that specific supplementation with DHA could be used to increase levels of the epoxy compound 19,20-EDP with potential anti-tumor activity in HCC patients receiving sorafenib therapy.
To determine the safety and efficacy of computed tomography (CT)-guided brachytherapy in hepatocellular carcinoma (HCC).
A total of 83 patients were recruited, presenting with 140 HCC- lesions. ...Treatment was performed by CT-guided high-dose-rate (HDR) brachytherapy with an iridium-192 source. The primary endpoint was time to progression; secondary endpoints included local tumor control and overall survival (OS). A matched-pair analysis with patients not receiving brachytherapy was performed. Match criteria included the Cancer of the Liver Italian Program (CLIP) score, alpha-fetoprotein, presence, and extent of multifocal disease. For statistical analysis, Kaplan-Meier and Cox regression were performed.
Mean and median cumulative TTP for all patients (n = 75) were 17.7 and 10.4 months. Five local recurrences were observed. The OS after inclusion reached median times of 19.4 months (all patients), 46.3 months (CLIP score, 0), 20.6 months (CLIP score, 1) 12.7 months, (CLIP score, 2), and 8.3 months (CLIP score, >or=3). The 1- and 3-year OS were 94% and 65% (CLIP score, 0), 69% and 12% (CLIP score, 1), and 48% and 19% (CLIP score, 2), respectively. Nine complications requiring intervention were encountered in 124 interventions. Matched-pair analysis revealed a significantly longer OS for patients undergoing CT-guided brachytherapy.
Based on our results the study treatment could be safely performed. The study treatment had a beneficial effect on OS in patients with advanced HCC, with respect to (and depending on) the CLIP score and compared with OS in a historical control group. A high rate of local control was also observed, regardless of applied dose in a range of 15 to 25 Gy.
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