Bieke Lambert
Ghent University, Nuclear Medicine, Faculty Member
Research Interests:
ABSTRACT
Research Interests:
Liver transplantation has become an important curative treatment option for hepatocellular carcinoma (HCC). Criteria for transplantation are strict and, therefore, it is crucial that patients awaiting transplantation do not suffer disease... more
Liver transplantation has become an important curative treatment option for hepatocellular carcinoma (HCC). Criteria for transplantation are strict and, therefore, it is crucial that patients awaiting transplantation do not suffer disease progression. One of the therapeutic options to achieve disease stabilization is neoadjuvant radiolabeled lipiodol treatment. This study aimed to document the dropout rate on the waiting list, the pathological findings on the explant livers, and the long-term outcome of patients treated with radionuclide therapy while awaiting transplantation. Patients eligible for transplantation were treated with 2.1 GBq (131)I-lipiodol or 4.1 GBq (188)Re-HDD/lipiodol by transfemoral catheterization of the hepatic arteries. Tumor necrosis was assessed in the explant livers and follow-up data, such as dropout from the waiting list, recurrence, and survival following transplantation were retrospectively documented. In 5 of 22 explants, necrosis exceeded 90%. Two patients died while on the waiting list (10%) and 4 of 20 transplanted patients (20%) suffered recurrent disease. The overall recurrence-free survival was 19.7 months (range, 1.75-56), with a mean follow-up of 20.1 months. Our data support the evaluation on larger patient numbers to confirm the benefit of radiolabeled lipiodol in candidates for liver transplantation who are suffering from HCC.
Research Interests:
Liver dissemination is a major cause of mortality among patients with advanced colorectal cancer. Hepatic intra-arterial injection of the beta-emitting isotope yttrium-90 ((90)Y) bound to resin microspheres (radioembolization) delivers... more
Liver dissemination is a major cause of mortality among patients with advanced colorectal cancer. Hepatic intra-arterial injection of the beta-emitting isotope yttrium-90 ((90)Y) bound to resin microspheres (radioembolization) delivers therapeutic radiation doses to liver metastases with minimal damage to adjacent tissues. We conducted a prospective, multicenter, randomized phase III trial in patients with unresectable, chemotherapy-refractory liver-limited metastatic CRC (mCRC) comparing arm A (fluorouracil [FU] protracted intravenous infusion 300 mg/m(2) days 1 through 14 every 3 weeks) and arm B (radioembolization plus intravenous FU 225 mg/m(2) days 1 through 14 then 300 mg/m(2) days 1 through 14 every 3 weeks) until hepatic progression. The primary end point was time to liver progression (TTLP). Cross-over to radioembolization was permitted after progression in arm A. Forty-six patients were randomly assigned and 44 were eligible for analysis (arm A, n = 23; arm B, n = 21). Median follow-up was 24.8 months. Median TTLP was 2.1 and 5.5 months in arms A and B, respectively (hazard ratio [HR] = 0.38; 95% CI, 0.20 to 0.72; P = .003). Median time to tumor progression (TTP) was 2.1 and 4.5 months, respectively (HR = 0.51; 95% CI, 0.28 to 0.94; P = .03). Grade 3 or 4 toxicities were recorded in six patients after FU monotherapy and in one patient after radioembolization plus FU treatment (P = .10). Twenty-five of 44 patients received further treatment after progression, including 10 patients in arm A who received radioembolization. Median overall survival was 7.3 and 10.0 months in arms A and B, respectively (HR = 0.92; 95% CI, 0.47 to 1.78; P = .80). Radioembolization with (90)Y-resin microspheres plus FU is well tolerated and significantly improves TTLP and TTP compared with FU alone. This procedure is a valid therapeutic option for chemotherapy-refractory liver-limited mCRC.
Research Interests:
Research Interests:
The use of 5-fluorouracil, topotecan, or gemcitabine was tested for enhancement of the effects of low dose rate (LDR) irradiation in an in vitro model for hepatocellular carcinoma. For comparison, all drugs were tested in combination with... more
The use of 5-fluorouracil, topotecan, or gemcitabine was tested for enhancement of the effects of low dose rate (LDR) irradiation in an in vitro model for hepatocellular carcinoma. For comparison, all drugs were tested in combination with high dose rate (HDR) gamma-irradiation as well. Multicellular spheroids of HepG2 cells were exposed to HDR or LDR irradiation by means of external beam cobalt-60 or rhenium-188 (188Re), respectively, dissolved in the culture medium. Secondly, exposure to irradiation was combined with the cytotoxic drug. Toxicity was evaluated by means of a quantitative spheroid outgrowth assay and histology. For 5-fluorouracil, supra-additive effects were observed in combination with HDR irradiation. With 188Re, the supra-additive toxicity was only transient. For topotecan and 188Re, no supra-additive effects were seen, whereas the addition of HDR irradiation at the end of the topotecan exposure yielded lasting supra-additive effects. Incubation with gemcitabine fo...
Research Interests:
Several techniques have been developed for radionuclide therapy of hepatocellular carcinoma (HCC). Medical literature databases (Pubmed, Medline) were screened for available literature and articles were critically analysed as to their... more
Several techniques have been developed for radionuclide therapy of hepatocellular carcinoma (HCC). Medical literature databases (Pubmed, Medline) were screened for available literature and articles were critically analysed as to their scientific relevance. In a palliative setting, intra-arterial administration of 131I-Lipiodol yields responses in 17-92% of patients. According to a randomised study, 131I-Lipiodol was far better tolerated than classic chemo-embolisation. The additive value of a single 131I-Lipiodol administration following partial liver resection for HCC was evaluated and evidence is available that adjuvant radionuclide treatment reduces the recurrence rate. Data concerning the role of 131I-Lipiodol in bridging patient to liver transplantation are scarce but suggest a potential benefit in terms of reducing the drop-out rate while patients are listed for transplantation. 188Re- and 90Y-labelled conjugates are emerging and initial clinical data are promising. Treatment ...
Research Interests:
Research Interests: Radiation Protection, Nuclear medicine, Treatment Outcome, Risk assessment, Nuclear, and 14 moreThyroid Cancer, Humans, Male, Bone marrow, Clinical Sciences, Aged, Middle Aged, Radiometry, Radiation Injuries, Risk Assessment, Radiopharmaceuticals, Recombinant Proteins, Thyroid Stimulating Hormone, and Platelet Count
Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. A wide variety of treatment modalities is available for palliative therapy of HCC, although there is no strong evidence that these treatments can have a... more
Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. A wide variety of treatment modalities is available for palliative therapy of HCC, although there is no strong evidence that these treatments can have a significant impact on survival. The aim of this work was to screen cytotoxic drugs relevant in the treatment of HCC for enhancement of the effect of irradiation in an in vitro model. As the majority of patients presenting with HCC suffer reduced liver function, attention was paid to low-dose effects of the cytotoxic drugs tested. To reflect this situation in vivo, multicellular tumor aggregates or "spheroids" of HepG2 cells were cultured and exposed to gamma irradiation alone or in combination with cisplatin for 4 h, gemcitabin for 4 or 24 h, or 5-fluorouracil for 4 h. In one experiment, the spheroids were cultured for 4 weeks in multiwell plates that allowed adhesion. Measurement of two-dimensional spheroid outgrowth was made every week for each spheroid. This kind of growth depends on the proliferation and motility of the cells that form the spheroid. In a second experiment, toxicity was evaluated by comparative growth curves by means of a three-dimensional growth assay and by histology. Supra-additive effects lasting for 4 weeks were observed for all drugs tested in combination with a gamma irradiation of 10 Gy.
Research Interests:
Research Interests:
During the past 10 years, a variety of radiolabeled monoclonal antibodies, antibody fragments, and low-molecular- weight oncophilic peptides have been used to deliver radioactivity to target cells for therapeutic purposes. The high and... more
During the past 10 years, a variety of radiolabeled monoclonal antibodies, antibody fragments, and low-molecular- weight oncophilic peptides have been used to deliver radioactivity to target cells for therapeutic purposes. The high and persistent localization of several of these radiolabeled molecules in the kidneys raised concern about potential renal radiation toxicity compromising therapeutic effectiveness. In particular, radiolabeled peptides, such as yttrium-90-labeled synthetic somatostatin analogues, have initiated a discussion on the safety profiles of the various somatostatin derivatives in recent clinical trials. In general, the toxicity risk seems to depend on the characteristics of the oncophilic molecule, such as the molecular weight, electric charges and clearance pathways as well as the chemical and physical characteristics of the applied radionuclide. Encouraging results for the prevention of radiation-induced renal damage by radiolabeled peptides have been obtained by co-infusion of positively charged amino acids. The available literature on nephrotoxicity after radiolabeled peptide therapy is reviewed, and therapeutic options that have become available as a result of greater insights into putative pathogenic mechanisms are discussed.
Research Interests:
Liver dissemination is a major cause of mortality among patients with advanced colorectal cancer. Hepatic intra-arterial injection of the beta-emitting isotope yttrium-90 ((90)Y) bound to resin microspheres (radioembolization) delivers... more
Liver dissemination is a major cause of mortality among patients with advanced colorectal cancer. Hepatic intra-arterial injection of the beta-emitting isotope yttrium-90 ((90)Y) bound to resin microspheres (radioembolization) delivers therapeutic radiation doses to liver metastases with minimal damage to adjacent tissues. We conducted a prospective, multicenter, randomized phase III trial in patients with unresectable, chemotherapy-refractory liver-limited metastatic CRC (mCRC) comparing arm A (fluorouracil [FU] protracted intravenous infusion 300 mg/m(2) days 1 through 14 every 3 weeks) and arm B (radioembolization plus intravenous FU 225 mg/m(2) days 1 through 14 then 300 mg/m(2) days 1 through 14 every 3 weeks) until hepatic progression. The primary end point was time to liver progression (TTLP). Cross-over to radioembolization was permitted after progression in arm A. Forty-six patients were randomly assigned and 44 were eligible for analysis (arm A, n = 23; arm B, n = 21). Median follow-up was 24.8 months. Median TTLP was 2.1 and 5.5 months in arms A and B, respectively (hazard ratio [HR] = 0.38; 95% CI, 0.20 to 0.72; P = .003). Median time to tumor progression (TTP) was 2.1 and 4.5 months, respectively (HR = 0.51; 95% CI, 0.28 to 0.94; P = .03). Grade 3 or 4 toxicities were recorded in six patients after FU monotherapy and in one patient after radioembolization plus FU treatment (P = .10). Twenty-five of 44 patients received further treatment after progression, including 10 patients in arm A who received radioembolization. Median overall survival was 7.3 and 10.0 months in arms A and B, respectively (HR = 0.92; 95% CI, 0.47 to 1.78; P = .80). Radioembolization with (90)Y-resin microspheres plus FU is well tolerated and significantly improves TTLP and TTP compared with FU alone. This procedure is a valid therapeutic option for chemotherapy-refractory liver-limited mCRC.
Research Interests:
Research Interests:
Research Interests: Psychometrics, Palliative Care, Quality of life, Treatment Outcome, Feasibility Study, and 15 moreHumans, Female, Feasibility Studies, Male, Hepatocellular Carcinoma, Clinical Sciences, Cisplatin, European, Aged, Middle Aged, Questionnaires, Reproducibility of Results, Radiopharmaceuticals, Sensitivity and Specificity, and Radionuclide Therapy
Research Interests:
Research Interests: Nuclear medicine, Treatment Outcome, Phase I clinical trial design, Nuclear, Humans, and 17 moreLiver Cirrhosis, Female, Feasibility Studies, Blood sampling, Male, Hepatocellular Carcinoma, Clinical Sciences, Shell Half-Life, Aged, Middle Aged, Adverse Event, Disease Progression, Radiopharmaceuticals, Alpha Fetoprotein, Organometallic Compounds, Radionuclide Therapy, and Whole Body
Research Interests: Nuclear medicine, Radiotherapy, Colorectal cancer, Open Source, Europe, and 14 moreHepatocellular Carcinoma, Follow-up studies, Medical Device, Liver Transplantation, Radiofrequency Ablation, Clinical Sciences, Radioactive Tracers, Tyrosine Kinase Inhibitor, Liver cancer, Radiopharmaceuticals, Liver Failure, Microspheres, Aqueous Solution, and Reference Values
Research Interests:
Several techniques have been developed for radionuclide therapy of hepatocellular carcinoma (HCC). Medical literature databases (Pubmed, Medline) were screened for available literature and articles were critically analysed as to their... more
Several techniques have been developed for radionuclide therapy of hepatocellular carcinoma (HCC). Medical literature databases (Pubmed, Medline) were screened for available literature and articles were critically analysed as to their scientific relevance. In a palliative setting, intra-arterial administration of 131I-Lipiodol yields responses in 17-92% of patients. According to a randomised study, 131I-Lipiodol was far better tolerated than classic chemo-embolisation. The additive value of a single 131I-Lipiodol administration following partial liver resection for HCC was evaluated and evidence is available that adjuvant radionuclide treatment reduces the recurrence rate. Data concerning the role of 131I-Lipiodol in bridging patient to liver transplantation are scarce but suggest a potential benefit in terms of reducing the drop-out rate while patients are listed for transplantation. 188Re- and 90Y-labelled conjugates are emerging and initial clinical data are promising. Treatment of HCC with 90Y-labelled microspheres is likely as efficacious as treatment with radiolabelled Lipiodol but pretreatment 99mTc-MAA scintigraphy is required in order to exclude patients with significant lung shunting. Several antibodies targeting antigens expressed on HCC have been radiolabelled, almost exclusively with 131I, and evaluated in a preclinical or clinical setting. The use of radiolabelled Lipiodol and microspheres allows for selective targeting of HCC with limited toxicity. Prospective, randomised controlled trials demonstrating that both treatment modalities may provide a survival benefit in a palliative setting are mandatory. In addition, future research should focus on the complementary role of radionuclide treatment in patients at risk for recurrent disease following partial liver resection or while awaiting liver transplantation.
Research Interests:
The high recurrence rate after curative resection has stimulated the development of adjuvant treatment modalities, such as local embolization. This study was set up to investigate the anti-tumoral potential of neo-adjuvant 131I-lipiodol... more
The high recurrence rate after curative resection has stimulated the development of adjuvant treatment modalities, such as local embolization. This study was set up to investigate the anti-tumoral potential of neo-adjuvant 131I-lipiodol administration before liver transplantation. In this preliminary, prospective study we treated 10 consecutive HCC patients by intra-arterial injection of 131I-lipiodol into the hepatic artery followed by liver transplantation within 1-9 months (mean 3.4). After hepatic catheterization, 1332-2146 MBq (mean 1887 MBq) or 36-58 mCi (mean 51 mCi) was instilled as selective as possible, depending on the distribution of the tumors: non-selectively in the hepatic artery propria (n = 4), selectively in the right and/or left hepatic artery (n = 3) or super-selectively in segmental arteries (n = 3). Anti-tumoral activity was regarded as obvious with 1) a strong decrease of alfa-fetoprotein (AFP), comparing the highest recorded value before and after 131I-lipiodol and/or 2) a downstaging in TNM classification on the posttherapy MRI as compared to the pre-therapy MRI and/or 3) tumors with > 50% necrosis on histo-pathology of the explanted liver, without previous chemoembolization. Either of these criteria were met by 5/10 (50%) of patients. A 4) downstaging in pTNM classification on histopathology compared to the TNM classification of the MRI and/or a 5) tumor necrosis of only 10-50% were regarded as possibly tumor-related but were not accepted as a single criteria of anti-tumoral activity. This was seen in 3/10 (30%) of patients. Clinical side-effects of the 131I-lipiodol therapy were generally mild with a temperature rise in two cases, nausea without vomiting in another two and upper back pain in one patient. In one patient progressive liver failure developed one week after 131I-lipiodol therapy necessitating premature liver transplantation after 4 weeks. With the use of stringent anti-tumoral criteria, this study shows evidence of an anti-tumoral effect in 50% of patients. Our data support the evaluation on larger patient numbers to confirm the promising anti-tumoral activity of 131I-lipiodol in HCC patients candidated for liver transplantation.
Research Interests:
The use of 5-fluorouracil, topotecan, or gemcitabine was tested for enhancement of the effects of low dose rate (LDR) irradiation in an in vitro model for hepatocellular carcinoma. For comparison, all drugs were tested in combination with... more
The use of 5-fluorouracil, topotecan, or gemcitabine was tested for enhancement of the effects of low dose rate (LDR) irradiation in an in vitro model for hepatocellular carcinoma. For comparison, all drugs were tested in combination with high dose rate (HDR) gamma-irradiation as well. Multicellular spheroids of HepG2 cells were exposed to HDR or LDR irradiation by means of external beam cobalt-60 or rhenium-188 (188Re), respectively, dissolved in the culture medium. Secondly, exposure to irradiation was combined with the cytotoxic drug. Toxicity was evaluated by means of a quantitative spheroid outgrowth assay and histology. For 5-fluorouracil, supra-additive effects were observed in combination with HDR irradiation. With 188Re, the supra-additive toxicity was only transient. For topotecan and 188Re, no supra-additive effects were seen, whereas the addition of HDR irradiation at the end of the topotecan exposure yielded lasting supra-additive effects. Incubation with gemcitabine followed by exposure to HDR irradiation, induced a synergistic toxicity on the outgrowth. No supra-additive effects were observed when HDR irradiation was added at the start of the incubation with gemcitabine or combined with LDR irradiation. For all drugs tested, supra-additive effects were observed with HDR irradiation if the timing of the irradiation was appropriate. For 188Re, no lasting supra-additive effects were observed.