Role of rapid arc-image-guided radiotherapy in hepatocellular carcinoma with portal vein tumor thrombosis: A study from tertiary care center in Punjab, India.

Background and Objectives: Treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is very challenging with poor outcome. In this situation, radiotherapy has become an alternative treatment modality, more precisely due to advances in radiation techniques. The goal of our study is to do analysis of these patients treated with rapid arc image-guided technology (RA-IGRT) at our institution. Materials and Methods: Thirteen patients were included in the study. As per intuition policy, patient set up, contouring, and treatment plans were generated. Radiological response assessment was done 1-month post-radiotherapy. Survival analysis curve along with Chi-square test for prognostic factors assessment was done using SPSS. Results: With median dose of 45 Gy in 20 fractions, we were able to achieve 27.3% objective response rate with median survival of 5 months in eligible patients. Conclusions: One-year overall survival up to 30% can be achieved in HCC with PVTT, especially in patients with objective response to radiotherapy with Japan Integrated Staging score 2, provided it is precisely hit by RA-IGRT.

Dose perturbation and inhomogeneity of multi-arrays of 125I seed-loaded stent for treatment of portal vein tumor thrombosis.

PURPOSE: To investigate the dosimetry of 125I seed-loaded stent system currently used for an adjuvant treatment of portal vein tumor thrombosis (PVTT). METHODS: The stent system consisted of an inner metallic stent and outer seed-loaded capsules. Four arrays of 125I seeds were attached longitudinally to the outer surface of the stent at 90° separation. 145 Gy was prescribed at 5 mm from the axes of seed-arrays. For the geometries of the 4-array, and potential 6- and 8-array configurations, treatment planning system (TPS) and Monte Carlo (MC) calculations were performed to evaluate 3D dose distributions and dosimetric impact of the metallic stent. RESULTS: The MC simulations indicated the metallic stent reduced a dose to the prescription points by over 10%, compared to the water-based TPS results. The total activity calculated by the water-based TPS to deliver the prescription dose should compensate for this amount of reduction. The MC- and TPS-calculated doses normalized to the prescription points for the current configuration were in agreements within 4.3% on a cylindrical surface along 5 mm from the axes of seed-arrays. The longitudinal underdosage worsened as approaching the edge of arrays, and ranged from 2.8% to 25.5%. The angular underdosage between neighboring arrays was 2.1%-8.9%. CONCLUSIONS: With this compensation and a special care of near-edge underdosage, the current 4-array system can provide adequate dose coverage for treatment of PVTT. Further dosimetric homogeneity can be achieved using 6-or 8-array configurations.

90Y-Loaded Microsphere SIRT of HCC Patients With Portal Vein Thrombosis: High Clinical Impact of 99mTc-MAA SPECT/CT-Based Dosimetry.

Radioembolization with 90Y-loaded microspheres based on classical prescription methods is increasingly applied to hepatocellular carcinoma (HCC) patients with portal vein thrombosis (PVT). In recent years, pretherapeutic predictive dosimetry based on technetium-99m macroaggregated albumin (MAA) quantitative scintigraphy using SPECT/CT has been developed. This paper presents an overview on the MAA-based dosimetry concept, discusses important confounding factors, such segmentation methods, and specific angiographic considerations required for a simulation-based dosimetric evaluation. The concept of "dosimetric angiography" is then introduced for the first time. Main results available are reported as a threshold tumor dose, allowing a response, between 100 and 120 Gy with 90Y-loaded resin microspheres and between 205 and 257 Gy with 90Y-loaded glass microspheres. Impact of MAA-based dosimetry and MAA PVT targeting on overall survival is also reported. Due to those dosimetric advances, personalized dosimetric approaches based on MAA dosimetry are now available, with specific endpoints, for both 90Y-loaded resin or glass microsphere. The clinical impact of personalized dosimetry in PVT patients is particularly high, as a median overall survival of 20.2 months has been reported for good PVT candidate treated with glass microspheres (tumor-absorbed dose ≥205 Gy and good PVT targeting) as against only 3 months for poor candidate (tumor-absorbed dose <205 Gy or poor PVT targeting), and as a significant amount of patients where downstaged and resected (12%) in the same study.

[A Case of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus Successfully Treated by Three-Dimensional Conformal Radiotherapy].

A man in his 50s was referred to our hospital with a liver tumor detected by ultrasonography during a medical checkup. Enhanced CT scan and MRI showed hepatocellular carcinoma(HCC)in S8 of the liver. Laparoscopic partial hepatectomy was performed. The histopathological findings showed well differentiated HCC. Two years later, his serum PIVKA-Ⅱ levels were slightly elevated. A new lesion was detected by US, CT, and MRI at S5 of the liver. A second laparoscopic partial hepatectomy was performed. The histopathological findings showed moderately differentiated HCC. After 1 year, MRI detected 2 new HCCs(S4, S8). The tumor at S8 had invaded the right branch of the portal vein. There was no indication for right hepatectomy because of liver dysfunction. Lipiodol-TACE followed by DEB-TACE was not effective on the tumor. The HCC at S8 had enlarged and formed a portal vein tumor thrombus. PIVKA- / Ⅱ levels increased to 3,596 mAU/mL. The patient was adminis- tered Three-dimensional conformal radiotherapy(45 Gy/15 Fr)and his PIVKA-Ⅱ levels decreased to the normal range. He has been followed-up without recurrences for 2 years and 9 months.

High-biologically effective dose palliative radiotherapy for a tumor thrombus might improve the long-term prognosis of hepatocellular carcinoma: a retrospective study.

BACKGROUND: This study aimed to highlight the type of tumor thrombus and identify the prognostic factors influencing the long-term survival outcomes in patients with hepatocellular carcinoma (HCC) having a tumor thrombus. A tumor thrombus in HCC is associated with poor prognosis. METHODS: Eighty patients diagnosed with HCC having a tumor thrombus between May 2006 and April 2014 were enrolled in this study. Age, gender, clinical characteristics, laboratory findings, Child-Pugh classification, performance status (ECOG), types of tumor thrombi, radiotherapy method, biologically effective dose (BED), and primary treatment method were analyzed to identify the prognostic factors associated with the overall survival (OS) rates. Statistical analyses were performed using SPSS version 19.0. RESULTS: The median follow-up duration was 24 months (range 6-90). The 1-, 3-, and 5-year OS rates of the patients were 77.6%, 37.6%, and 18.8%, respectively. On univariate analysis, gender, radiotherapy method, BED, types of tumor thrombi, Child-Pugh classification, ECOG, and total bilirubin were associated with OS (P < 0.001, P = 0.001, P = 0.016, P = 0.003, P < 0.001, P < 0.001, P = 0.039, respectively). The prognostic factors for OS in multi-variate analyses were gender (P < 0.001), BED (P = 0.044), Child Pugh classification (P = 0.020), performance status (ECOG) (P = 0.004), and types of tumor thrombi (P = 0.001). The median OS for the high-BED group was better than that for the low-BED groups (42 months vs. 19 months, P = 0.016). CONCLUSIONS: Gender, BED, performance status (ECOG), Child-Pugh classification, and types of tumor thrombi seemed to affect OS, and a stepwise decrease in survival was observed with the types of tumor thrombi ranging from I to IV. High-BED palliative radiotherapy might improve the long-term outcomes for patients with HCC having a tumor thrombus.

Effects of cryoablation and radiofrequency ablation on endothelial and blood clotting activation.

Cryoablation (CA) emerged as an alternative procedure to radiofrequency (RF). The aim of this study was to compare haemostatic system alterations in patients undergoing RF or CA for atrioventricular nodal reentrant tachycardia ablation. von Willebrand factor (vWF), spontaneous whole blood platelet aggregation, prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), plasminogen activator inhibitor type-1 (PAI-1), and clot lysis time (CLT) were determined in 48 patients (27 CA; 21 RF; 19M/29F, mean age 49.6 ± 17.6 years). Blood samples were obtained before the procedure (T0), immediately after (T1), and 24 h later (T2). At T1 both procedures were associated with a significant increase in levels of the endothelial activation marker vWF. At T2 vWF levels were lower in CA than in RF group. No changes in whole blood platelet aggregation before and after ablation procedures were observed. At T1 both groups determined an increase in blood clotting activation markers, F1 + 2, TAT, and DD. At T2 F1 + 2, TAT and DD levels were similar to baseline values. The comparison between RF and CA showed no significant differences in F1 + 2 and TAT levels, whereas at T1 DD levels were higher in CA group than in RF group. Both procedures induced a significant decrease in CLT, whereas no changes in PAI-1 levels were found. There were no significant differences in CLT and PAI-1 levels. The fibrinolytic efficiency analysis showed that at T1 DD/TAT and DD/F1 + 2 ratios were lower in RF group and remained lower in RF than in CA group at T2. CA procedure may be associated with a lower degree of endothelial damage and with a higher fibrinolytic capacity respect to RF.

Effectiveness and safety of proton beam therapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis.

PURPOSE: To evaluate the clinical effectiveness and safety of proton beam therapy (PBT) in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). PATIENTS AND METHODS: Twenty-seven HCC patients with PVTT underwent PBT, including 22 patients with modified International Union Against Cancer (mUICC) stage IVA,five patients with stage IVB primary tumors, and 16 with main PVTT. A median dose of 55 GyE (range, 50-66 GyE) in 20-22 fractions was delivered to a target volume encompassing both the PVTT and primary tumor. RESULTS: Overall, treatment was well tolerated, with no toxicity of grade ≥ 3. Median overall survival (OS) times in all patients and in stage IVA patients were 13.2 months and 16 months, respectively. Assessments of PVTT response showed complete response in 0 of 27 (0%) patients, partial response in 15 (55.6%), stable disease in 10 (37%), and progressive disease in 2 (7.4%) patients, with an objective response rate of 55.6%. PVTT responders showed significantly higher actuarial 1-year local progression-free survival (LPFS; 85.6% vs. 51.3%), relapse-free survival (RFS; 20% vs. 0%) and OS (80% vs. 25%) rates than nonresponders (p<0.05 each). Multivariate analysis showed that PVTT response and mUICC stage were independent prognostic factors for OS. CONCLUSION: Our data suggest that PBT could improve LPFS, RFS, and OS in advanced HCC patients with PVTT and it is feasible and safe for these patients.

Iodine-125 seeds strand for treatment of tumor thrombus in inferior vena cava: an experimental study in a rabbit model.

OBJECTIVE: The purpose of this study was to establish an animal model of implanted inferior vena cava tumor thrombus (IVCTT) and to evaluate the effect of linear iodine-125 seeds strand in treating implanted IVCTT. METHODS: Tumor cell line VX2 was inoculated subcutaneously into New Zealand rabbit to develop the parent tumor. The tumor strip was inoculated into inferior vena cava (IVC) to establish the IVCTT model. The IVCTT was confirmed by multidetector computed tomography (MDCT) after 2 weeks. Twelve rabbits with IVCTT were randomly divided into two groups. Treatment group (group T; n = 6) underwent Iodine-125 seeds brachytherapy, and the control group (group C; n = 6) underwent blank seeds strand. The blood laboratory examination (including blood routine examination, hepatic and renal function), body weight, survival time, and IVCTT volume by MDCT were monitored. All rabbits were dissected postmortem, and the therapeutic effects were evaluated on the basis of histopathology. The proliferating cell nuclear antigen index (PI) and apoptosis index (AI) of IVCTT were compared between two groups. T test, Wilcoxon rank test, and Kaplan-Meier survival curve analysis were used. RESULTS: The success rate of establishing IVCTT was 100 %. The body weight loss and cachexia of rabbits in group C appeared earlier than in group T. Body weight in the third week, the mean survival time, PI, AI in groups T and C were 2.23 ± 0.12 kg, 57.83 ± 8.68 days, (16.73 ± 5.18 %), (29.47 ± 7.18 %), and 2.03 ± 0.13 kg, 43.67 ± 5.28 days, (63.01 ± 2.01 %), (6.02 ± 2.93 %), respectively. There were statistically significant differences between group T and group C (P < 0.05). The IVCTT volume of group T was remarkably smaller than that of group C. CONCLUSIONS: Injecting and suspensory fixing VX2 tumor strip into IVC is a reliable method to establish IVCTT animal model. The linear Iodine-125 seeds strand brachytherapy was a safe and effective method for treating IVCTT in rabbit model.

A dose-volume intercomparison of volumetric-modulated arc therapy, 3D static conformal, and rotational conformal techniques for portal vein tumor thrombus in hepatocellular carcinoma.

We created volumetric-modulated arc therapy (VMAT) plans for portal vein tumor thrombus (PVTT) in hepatocellular carcinoma, and compared the results with those from three-dimensional conformal radiotherapy (3D-CRT) and rotational conformal radiotherapy (R-CRT) plans. CT scan data from 10 consecutive patients with PVTT treated with 3D-CRT between January 2008 and January 2010 were utilized in the analysis. We analyzed the dosimetric properties of the plans for the 10 patients using the three different techniques with three different isocenter doses of 50, 56 and 60 Gy in 2-Gy fractions. The D95, Dmean, homogeneity index and conformity index were compared for the planning target volume (PTV). The Dmean, V20 and V30 were also compared for normal livers. The monitor units (MUs) and the treatment time were also evaluated. The normal liver V30 for VMAT was significantly less than that for 3D-CRT for the prescribed doses of 56 and 60 Gy (P < 0.05). It was also found that the normal liver V30 resulting from 3D-CRT was prohibitively increased when the prescribed dose was increased in two steps. For PTV D95, we found no significant differences between the three techniques for the 50- and 56-Gy prescriptions, or between VMAT and the other techniques for the 60-Gy prescription. The differences in the MUs and treatment times were not statistically significant between VMAT and 3D-CRT. We have demonstrated that VMAT may be a more advantageous technique for dose escalation reaching 60 Gy in the treatment of PVTT due to the reduced normal liver V30.

Comparison of coplanar and noncoplanar intensity-modulated radiation therapy and helical tomotherapy for hepatocellular carcinoma.

BACKGROUND: To compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT). METHODS: Nine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to deliver 46-54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of whole normal liver (V30<30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose, percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs at risk were evaluated from the dose-volume histogram. RESULTS: HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17% vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the normal liver could be less than 20 Gy and 25 Gy, respectively. CONCLUSION: Noncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT. Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.

Combination of transarterial chemoembolization and three-dimensional conformal radiotherapy for hepatocellular carcinoma with inferior vena cava tumor thrombus.

PURPOSE: To evaluate the effects of transarterial chemoembolization (TACE) and three-dimensional conformal radiotherapy (CRT) in patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT). METHODS AND MATERIALS: A total of 42 consecutive patients who underwent TACE and CRT (TACE+CRT group) for the treatment of HCC with IVCTT were prospectively enrolled from July 2004 to October 2006. As historical controls, 29 HCC patients with IVCTT who received TACE alone (TACE group) between July 2003 and June 2004 were included. CRT was designed to target only the IVCTT and to deliver a median total dose of 45 Gy (range, 28-50 Gy). RESULTS: Most baseline characteristics of the two groups were similar (p > 0.05). The response and progression-free rates of IVCTT were significantly higher in the TACE+CRT group than in the TACE group (42.9% and 71.4% vs. 13.8% and 37.9%, respectively; p < 0.01 for both rates). Overall, patient survival was significantly higher in the TACE+CRT group than in the TACE group (p < 0.01), with a median survival time of 11.7 months and 4.7 months, respectively. Treatment with TACE+CRT (hazard ratio [HR] = 0.38; 95% confidence interval [CI], 0.20-0.71), progression of IVCTT (HR = 4.05; 95% CI, 2.00-8.21), Child-Pugh class B (HR = 3.44; 95% CI, 1.79-6.61), and portal vein invasion (HR = 2.31; 95% CI, 1.19-4.50) were identified as independent predictors of mortality by multivariable analysis. CONCLUSIONS: The combination of TACE and CRT is more effective in the control of IVCTT associated with HCC and improves patient survival compared with TACE alone.

A case of hepatocellular carcinoma initially treated by carbon ions, followed by protons for marginal recurrence with portal thrombus.

We report a case of hepatocellular carcinoma (HCC), initially treated by carbon ions, then subsequently by protons for marginal recurrence. A 52-year-old man with stage II HCC was enrolled in the clinical study for carbon ion therapy. A total dose of 52.5 GyE in 8 fractions was delivered through a right lateral port for 13 days. Dynamic CT performed 7 months after the initiation of carbon ion therapy showed a decrease in the size of the tumor. Dynamic CT performed 12 months after the therapy revealed marginal recurrence of HCC accompanied with portal vein tumor thrombus (PVTT). Proton therapy of 66 GyE in 22 fractions was delivered through posterior and right lateral ports for 33 days. Dynamic CT performed 3 months after the initiation of proton therapy showed a regression of the recurrent tumor and disappearance of the PVTT. No serious adverse effects were observed during or after these two treatments. He was free from further recurrence 27 months after the initiation of the first carbon ion therapy. Both carbon ions and protons were effective with minimal side effects.

Peptide radiopharmaceuticals for diagnosis and therapy.

Radiolabelled peptides are an emerging class of radiopharmaceuticals that share chemical and biological properties. From the chemical point of view they have a poly-amino acid structure varying from 3 to more that 200 amino acids, and they are labelled with different isotopes directly or by a linker. Biologically, they bind to specific cell membrane receptors, thus providing in vivo histopathological information for diagnostic purposes, therapy follow-up or targeted radiotherapy. This paper reviews most of the radiolabelled peptides that have been tested in animals and humans in the fields of oncology, neurology, cardiology, inflammation/infection, atherosclerosis and thrombosis. A new classification is also proposed for peptides targeting tumour cells based on the biological function of target receptors. These tailored radiopharmaceuticals are the basis of the new era of "molecular nuclear medicine".

Late stent thrombosis without antecedent brachytherapy: confirmation and treatment with rheolytic thrombectomy.

We describe two cases of late stent thrombosis (> 30 days postprocedure) following stenting without brachytherapy. Stent thrombosis was confirmed after successful treatment by catheter-based rheolytic thrombectomy. Predictors of stent thrombosis are reviewed and issues concerning the duration of combination antiplatelet therapy after stenting are discussed.

Utilidad de la braquiterapia intravascular en la prevención de la reestenosis secundaria a angioplastia transluminal coronaria / Efficacy of the intravascular brachytherapy for the prevention of the secondary restenosis to the transluminal coronary angioplasty

La radioterapia intravascular coronaria ha demostrado de manera convincente en estudios clínicos y experimentales que produce una disminución favorable del proceso de reestenosis. Hay evidencia suficiente para definir a dicha técnica como la principal terapia actual en el manejo de la reestenosis intra stent. Existe experiencia acumulada de hasta 3 años en pacientes tratados con radiación gamma y múltiples estudios en varios centros demuestran beneficios similares con emisores beta. Como efectos adversos de la braquiterapia se han descrito el desarrollo de nuevas estenosis en los márgenes de la lesión tratada (el ‘efecto borde’) y la oclusión trombótica tardía. A pesar de esto, la mayoría de investigadores cree que estos problemas pueden ser evitados y que la radiación intravascular es la terapia de elección en pacientes con alto riesgo de reestenosis tras intervención percutánea de revascularización coronaria. Ahora que se ha pasado de la experimentación animal a la fase clínica, y mientras la investigación continua, la tecnología está siendo optimizada para encontrar nuevas fuentes y vías de administración de la radiación que puedan ser lanzadas al mercado. El presente artículo revisa una serie de sistemas de radioterapia y hace una puesta al día sobre el empleo de la braquiterapia intravascular en pacientes cardiológicos (AU)

Intravascular radiotherapy has convincingly shown in several experimental and clinical studies to result in a marked and favorable control of the restenotic process. The evidence that radiation therapy constitutes a major breakthrough therapy for patients with in-stent restenosis is convincing, and the safety and long-lasting benefit with gamma-radiation at 3 years has been demonstrated. It is known that this benefit comes at the price of an excess of new stenoses at the lesion edge (the edge effect) and late (>1 month) thrombotic occlusion compared with control groups. However, investigators believe these problems can be avoided and that radiation therapy is the first-line treatment in this group of patients. Intravascular radiotherapy has moved from animal experiments via the safety and feasibility testing into the phase of clinical trials of efficacy in large numbers of patients. While ongoing research continues to search for new sources and delivery techniques, currently available technology is being optimized in pursuit advanced intravascular radiotherapy systems and resumes the principal issues of intravascular brachytherapy in the cardiology field (AU)

Management of peripheral vascular disease: innovative approaches using radiation therapy.

Despite the early successes at vascular recanalization with percutaneous transluminal angioplasty, vascular restenosis has emerged as a clinical problem of near epidemic proportions. Numerous pharmacologic and mechanical adjuncts have been tried with little success. Over the last few years, there have major advances in our understanding of the biology of the restenotic process. The process is now recognized as a proliferation disorder, and therapies akin to those used in the treatment of malignant diseases are being explored. Endovascular brachytherapy has shown strong potential in controlling this pathologic proliferative process in the laboratory and in early clinical studies. In this review we discuss some of the basic issues involved in vascular restenosis and the current status of endovascular brachytherapy.

[Early complications of radical prostatectomy. Pelvic vein compression caused by wound drainage]. / Frühkomplikation nach radikaler Prostatektomie. Beckenveneneinengung durch Wunddrainage.

Deep vein thrombosis and thromboembolism is a common complication following urologic pelvic surgery, with incidences up to 80% being reported. We report on a 71-year-old patient with prostate cancer, who showed clinical and radiological signs of pulmonary embolism with no evidence of a deep vein thrombosis 14 days after radical prostatectomy. Phlebography revealed compression of the left external iliac vein by the drainage tube as the potential cause of the pulmonary embolism. The drainage tube was repositioned under CT control. The ultrasound Doppler technique confirmed unimpaired flow in the left external iliac vein after repositioning. Drainage tubes should be positioned far enough medially to avoid compression of the iliac vessels.