Maciej Pech

Diffusion‐weighted magnetic resonance imaging allows monitoring of anticancer treatment effects in patients with soft‐tissue sarcomas

To determine if diffusion‐weighted imaging (DWI) can be used as a surrogate marker of tumor response to anticancer therapy in patients with soft‐tissue sarcomas.

Detection and characterisation of focal liver lesions in colorectal carcinoma patients: comparison of diffusion-weighted and Gd-EOB-DTPA enhanced MR imaging

ObjectiveTo compare diffusion-weighted imaging (DWI) and Gd-EOB-DTPA-enhanced magnetic resonance (MR) imaging for the detection and characterisation of focal liver lesions (FLLs) in patients with colorectal carcinoma.MethodsSeventy-three patients underwent MR imaging including echoplanar DWI (MR-DWI) and dynamic (MR-Dyn) and hepatobiliary phase (MR-Late) Gd-EOB-DTPA-enhanced images. Two blinded readers independently reviewed 5 different image sets using a 5-point confidence scale. Accuracy was assessed by the area (Az) under the receiver operating characteristic curve, and sensitivity and specificity were calculated.ResultsA total of 332 FLLs were evaluated. Detection rates were significantly higher for MR-Late images (94.4% for benign and 100% for malignant lesions) compared with MR-DWI (78.3% and 97.5%) and MR-Dyn images (81.5% and 89.9%). Accuracy was 0.82, 0.76 and 0.89 for MR-DWI, MR-Dyn and MR-Late images while sensitivity was 0.98, 0.87 and 0.95, respectively. For characterisation of subcentimetre lesions sensitivity was highest for MR-DWI (0.92). Combined reading of unenhanced and contrast-enhanced images had an identical high accuracy of 0.98.ConclusionLate-phase Gd-EOB-DTPA-enhanced images were superior for the detection of FLLs, while DWIs were most valuable for the identification of particularly small metastases. Combined interpretation of unenhanced images resulted in precise characterisation of FLLs.

Computed Tomography–Guided High-Dose-Rate Brachytherapy in Hepatocellular Carcinoma: Safety, Efficacy, and Effect on Survival

PURPOSE To determine the safety and efficacy of computed tomography (CT)-guided brachytherapy in hepatocellular carcinoma (HCC). METHODS AND MATERIALS 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. RESULTS 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. CONCLUSION 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.

Left‐liver hypertrophy after therapeutic right‐liver radioembolization is substantial but less than after portal vein embolization

In patients with liver malignancies potentially amenable to curative extended right hepatectomy but insufficient size of the future liver remnant (FLR), portal vein embolization (PVE) of the tumor‐bearing liver is used to induce contralateral liver hypertrophy but leaves the tumor untreated. Radioembolization (RE) treats the tumor in the embolized lobe along with contralateral hypertrophy induction. We performed a matched‐pair analysis to compare the capacity for hypertrophy induction of these two modalities. Patients with right‐hepatic secondary liver malignancies with no or negligible left‐hepatic tumor involvement who were treated by right‐lobar PVE (n = 141) or RE (n = 35) at two centers were matched for criteria known to influence liver regeneration following PVE: 1) baseline FLR/Total liver volume ratio (<25 versus ≥25%); 2) prior platinum‐containing systemic chemotherapy; 3) embolization of segments 5‐8 versus 4‐8; and 4) baseline platelet count (<200 versus ≥200 Gpt/L).The primary endpoint was relative change in FLR volume from baseline to follow‐up. Twenty‐six matched pairs were identified. FLR volume increase from baseline to follow‐up (median 33 [24‐56] days after PVE or 46 [27‐79] days after RE) was significant in both groups but PVE produced significantly more FLR hypertrophy than RE (61.5 versus 29%, P < 0.001). Time between treatment and follow‐up was not correlated with the degree of contralateral hypertrophy achieved in both groups. Although group differences in patient history and treatment setting were present and some bias cannot be excluded, this was minimized by the matched‐pair design, as remaining group differences after matching were found to have no significant influence on contralateral hypertrophy development. Conclusion: PVE induces significantly more contralateral hypertrophy than RE with therapeutic (nonlobectomy) doses. However, contralateral hypertrophy induced by RE is substantial and RE minimizes the risk of tumor progression in the treated lobe, possibly making it a suitable modality for selected patients. (Hepatology 2014;59:1864–1873)

CT-Guided Interstitial Brachytherapy of Primary and Secondary Lung Malignancies

Background and Purpose:CT-guided interstitial brachytherapy of primary lung malignancies and pulmonary metastases represents a novel interventional technique, combining conventional high-dose-rate (HDR) iridium-192 (192Ir) brachytherapy with modern CT guidance for applicator positioning and computer-aided 3-D radiation treatment planning. The purpose of this study was to assess safety and efficacy of this technique.Patients and Methods:30 patients with 83 primary or secondary lung malignancies were recruited in a prospective nonrandomized trial (Table 1). After catheter positioning under CT fluoroscopy, a spiral CT was acquired for treatment planning (Figure 1). All but two patients received a defined single dose (coverage > 99%) of at least 20 Gy from a 192Ir source in HDR technique.Results:Adverse effects were nausea (n = 3, 6%), minor (n = 6, 12%) and one major pneumothorax (2%). Post intervention, no changes of vital capacity and forced expiratory volume could be detected. The median follow-up period was 9 months (1–21 months) with a local tumor control of 91% at 12 months (Figure 2).Conclusion:CT-guided interstitial brachytherapy proved to be safe and effective for the treatment of primary and secondary lung malignancies.Hintergrund und Ziel:Die CT-gesteuerte interstitielle Brachytherapie von primären Lungenmalignomen und Lungenmetastasen stellt eine weiterentwickelte interventionelle Technik dar, welche die konventionelle Hochdosisraten-(HDR)-Iridium-192-(192Ir-)Brachytherapie mittels moderner CT-Bildführung zur Applikatorpositionierung und computergestützter 3-D-Bestrahlungsplanung kombiniert. Ziel der Studie war die Analyse von Sicherheit und Effektivität dieses Verfahrens.Patienten und Methodik:30 Patienten mit 83 primären Lungenmalignomen oder pulmonalen Metastasen wurden in einer prospektiven, nicht randomisierten Phase-II-Studie behandelt (Tabelle 1). Nach Katheterpositionierung unter CT-Fluoroskopie erfolgte die Gewinnung eines 3-D-Datensatzes für die Bestrahlungsplanung (Abbildung 1). Alle Patienten bis auf zwei erhielten eine vorgeschriebene Einzeldosis (Abdeckung > 99%) von mindestens 20 Gy über eine 192Ir-Quelle in HDR-Technik.Ergebnisse:Minorkomplikationen waren Übelkeit (n = 3, 6%), diskreter (n = 6, 12%) sowie ein therapiebedürftiger Pneumothorax (2%). Postinterventionell ergaben sich keine Änderungen der Vitalkapazität oder des forcierten exspiratorischen Volumens. Die mediane Nachbeobachtungszeit betrug 9 Monate (1–21 Monate). Die lokale Tumorkontrolle lag nach 12 Monaten bei 91% (Abbildung 2).Schlussfolgerung:Die CT-gesteuerte interstitielle HDR-Brachytherapie stellt ein sicheres und effektives Verfahren zur Behandlung von primären Lungenmalignomen und pulmonalen Metastasen dar.

Angiography in the Isolated Perfused Kidney: Radiological Evaluation of Vascular Protection in Tissue Ablation by Nonthermal Irreversible Electroporation

PurposeThe nonthermal irreversible electroporation (NTIRE) is a novel nonthermal tissue ablation technique by local application of high-voltage current within microseconds leading to a delayed apoptosis. The purpose of this experimental study was the first angiographic evaluation of the acute damage of renal vascular structure in NTIRE.MethodsResults of conventional dynamic digital substraction angiography (DSA) and visualization of the terminal vascular bed of renal parenchyma by high-resolution X-ray in mammography technique were evaluated before, during, and after NTIRE of three isolated perfused porcine ex vivo kidneys.ResultsIn the dedicated investigation, no acute vascular destruction of the renal parenchyma and no dysfunction of the kidney perfusion model were observed during or after NTIRE. Conspicuous were concentric wave-like fluctuations of the DSA contrast agent simultaneous to the NTIRE pulses resulting from NTIRE pulse shock wave.ConclusionThe NTIRE offers an ablation method with no acute collateral vascular damage in angiographic evaluation.

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

BackroundHepatic 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.Materials and methods23 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.ResultsAt 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.ConclusionHepatic 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.

Treatment of hepatic metastases of breast cancer with CT-guided interstitial brachytherapy - a phase II-study.

PURPOSE The aim of the study was the evaluation of feasibility, safety and effectiveness of interstitial brachytherapy for the treatment of hepatic metastases of breast cancer. MATERIALS AND METHODS Forty-one consecutive patients with 115 unresectable hepatic metastases of breast cancer were included in this phase-II-trial. They were treated in 69 interventions of CT-guided-interstitial-brachytherapy of the liver. Brachytherapy was applied as a single fraction high-dose-irradiation (15-25Gy (Gray)) using a (192)Ir-source of 10Ci. Nineteen patients presented systemically pretreated extrahepatic tumors. Primary endpoints were complications, local tumor control and progression-free survival. RESULTS The median tumor diameter was 4.6 cm (1.5-11 cm). The median irradiation time per intervention was 26.5 min (range: 7-47 min). The applied median minimal dose at the CTV (clinical target volume) margin was 18.5 Gy (12-25 Gy). In 69 interventions and during the postinterventional period, one major complication (symptomatic post-interventional bleeding) (1.5%) and six minor complications occurred (8.7%). The median follow-up time was 18 months (range: 1-56). After 6, 12 and 18 months, local tumor control was 97%, 93.5% and 93.5%, intra- and extrahepatic progression free survival was 53%, 40% and 27%, and overall survival was 97%, 79% and 60%, respectively. CONCLUSION CT-guided-brachytherapy is safe and effective for the treatment of liver metastases of breast cancer.

Radiotherapy of Liver Metastases Comparison of Target Volumes and Dose-Volume Histograms Employing CT- or MRI-Based Treatment Planning

Purpose:To assess differences in delineated target volumes of liver metastases using contrast-enhanced CT and different MRI sequences for radiation treatment planning.Patients and Methods:25 patients with 43 colorectal liver metastases were recruited. Tumor margins were defined by two experienced radiologists. The resulting D90 was assessed and the CT-based 3-D dose distribution merged with the according MRI dataset by employing image fusion. A theoretical D90 as a result of MRI-based treatment planning was assessed for various MRI sequences individually.Results:In venous phase contrast-enhanced CT, the mean tumor volume was 20 ml; T1-weighted (T1w) MRI, 27 ml; contrast-enhanced T1w 42 ml; T2w 65 ml. The difference between the target volumes as assessed by either CT or MRI was 181% for T1w images, 178% for contrast-enhanced T1w, and 246% for T2w sequences. All differences were statistically significant (p < 0.05).The analysis of the dose-volume histograms revealed statistically significant differences (i.e., for the D90) for the different target volumes specified by CT and MRI: mean D90 on CT, 18 Gy; plain T1w, 16 Gy; contrast-enhanced T1w, 15.5 Gy; T2w, 12 Gy. Hence, delineation of a larger target volume in T2w MRI compared to contrast-enhanced CT resulted in a smaller D90.The mean differences of tumor volumes assessed by CT and plain T1w were significantly higher in the group of patients showing local tumor recurrences as compared to patients with long-term local tumor control (p = 0.002).Conclusion:For treatment planning of liver metastases, the use of either plain T1w or T2w sequences is recommended to delineate the clinical target volume as completely as possible and not to miss potential tumor cell congregations in the surroundings as in CT.Ziel:Beurteilung von Unterschieden in der Abgrenzung von Zielvolumina bei kontrastmittelverstärkter CT- und MRT-gestützter Bestrahlungsplanung.Patienten und Methodik:25 Patienten mit 43 Lebermetastasen kolorektalen Ursprungs wurden in dieser Studie untersucht. Zur Definition der Zielvolumina wurden CT- und MRT-Untersuchungen verwendet, die Konturierung der Tumorränder wurde von zwei erfahrenen Radiologen vorgenommen. Die D90 wurde nach Bildfusionierung der CT-basierten dreidimensionalen Dosisverteilungen mit den MRT-Datensätzen beurteilt. Eine theoretische D90 als Resultat der MRT-basierten Bestrahlungsplanung wurde bestimmt.Ergebnisse:In der venösen Phase der kontrastmittelverstärkten CT-Untersuchung betrug das mittlere Tumorvolumen 20 ml; MRT T1-gewichtet (T1w) 27 ml; kontrastmittelverstärkte T1w 42 ml; T2w 65 ml. Die Unterschiede der Zielvolumina im Verhältnis zur CT-gestützten Planung betrugen 181% für T1w-, 178% für kontrastmittelverstärkte T1w- und 246% für T2w-Sequenzen. Alle Unterschiede stellten sich als signifikant heraus (p < 0,05). Im Vergleich zur kontrastmittelverstärkten CT resultierte somit das Bemessen des Tumorvolumens im T2w MRT in einer niedrigeren D90.Die Analyse der Dosis-Volumen-Histogramme zeigte signifikante Unterschiede der verschiedenen Volumina. Die mittlere D90 betrug bei CT 18 Gy, bei nativer T1w 16 Gy, bei kontrastmittelverstärkter T1w 15,5 Gy und bei T2w 12 Gy.Die mittleren Unterschiede des Zielvolumens durch CT- und native T1w-gestützte MRT-Bestrahlungsplanung waren in der Gruppe der Patienten mit lokalen Tumorrezidiven signifikant höher als in der Gruppe mit langfristiger lokaler Kontrolle (p = 0,002).Schlussfolgerung:Für die Bestrahlungsplanung der Therapie von Lebermetastasen wird die Verwendung von nativen T1w- oder T2w-Sequenzen zur Abgrenzung des Zielvolumens empfohlen, um eine möglichst vollständige Erfassung der Metastase einschließlich evtl. vorhandener peripherer Tumorausläufer zu erreichen.

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

BackgroundTo 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.MethodsTwenty 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 D90 as the BED exposing 90% of the pseudolesion in MRI.ResultsThe tolerance doses D90 after 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 D90 with 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 D90 and the pseudolesions 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.ConclusionsInactivation 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.