J. M. H. de Klerk

Bone Seeking Radiopharmaceuticals for Palliation of Pain in Cancer Patients with Osseous Metastases

Many patients with cancer develop symptomatic skeletal metastases at an advanced stage of their disease. Skeletal metastases are often complicated by pain. They cause considerable morbidity and mortality. Besides analgesics, treatment options include external beam radiotherapy, bisphosphonates, chemotherapy, surgery and bone seeking radiopharmaceuticals. Pain palliation with bone seeking radiopharmaceuticals has proved to be an effective treatment modality in patients with metastatic bone pain. Radiopharmaceuticals bind to the bone matrix in areas of increased bone turnover, due to a metastatic response. Beta rays from the specific radionuclide, bound to its carrier ligand, result in the therapeutic effect. Various radiopharmaceuticals have been developed for this purpose. All have their own characteristics. The radiopharmaceuticals Samarium-153-ethylenediaminetetramethylenephosphonic acid ((153)Sm-EDTMP) and Strontium-89-Chloride, which are approved in the USA and Europe, as well as the not universally approved Rhenium-186-hydroxyethylidenediphosphonic acid ((186)Re-HEDP), will be discussed in greater detail. Depending on the half-life and radiation energy of the specific radionuclide, they exert a different effect and toxicity profile. In most cases, bone marrow toxicity is limited and reversible, which makes repetitive treatment relatively safe. Several studies have shown encouraging clinical results of palliative therapy using bone seeking radiopharmaceuticals, with an overall reported pain response rate in the order of +/- 70-80% of patients. This systemic form of radionuclide therapy is simple to administer and complements other treatment options. It has been associated with marked pain reduction, improved mobility in many patients, reduced dependence on analgesics, and improved performance status and quality of life. Additionally, new therapeutic strategies hold the promise of enhancement of the palliative and anticancer effects of this form of therapy.

Systematic review and meta-analysis on the diagnostic performance of FDG-PET/CT in detecting bone marrow involvement in newly diagnosed Hodgkin lymphoma: is bone marrow biopsy still necessary?

BACKGROUND This study aimed to systematically review and meta-analyze published data on the diagnostic performance of (18)F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) in detecting bone marrow involvement in newly diagnosed Hodgkin lymphoma, and to determine whether FDG-PET/CT can replace blind bone marrow biopsy (BMB) in these patients. PATIENTS AND METHODS The PubMed/Medline and Embase databases were systematically searched for relevant studies. Methodological quality of each study was assessed. Sensitivities and specificities of FDG-PET/CT in individual studies were calculated and underwent meta-analysis with a random effects model. A summary receiver operating characteristic curve (sROC) was constructed with the Moses-Shapiro-Littenberg method. The weighted summary proportion of FDG-PET/CT-negative patients with a positive BMB among all cases was calculated under the fixed effects model. RESULTS Nine eligible studies, comprising a total of 955 patients with newly diagnosed Hodgkin lymphoma, were included. Overall, the studies were of moderate methodological quality. The sensitivity and specificity of FDG-PET/CT for the detection of bone marrow involvement ranged from 87.5% to 100% and from 86.7% to 100%, respectively, with pooled estimates of 96.9% [95% confidence interval (CI) 93.0% to 99.0%] and 99.7% (95% CI 98.9% to 100%), respectively. The area under the sROC curve was 0.9860. The weighted summary proportion of FDG-PET/CT-negative patients with a positive BMB among all cases was 1.1% (95% CI 0.6% to 2.0%). CONCLUSION Although the methodological quality of studies that were included in this systematic review and meta-analysis was moderate, the current evidence suggests that FDG-PET/CT may be an appropriate method to replace BMB in newly diagnosed Hodgkin lymphoma.

Fixed dosage of 131I for remnant ablation in patients with differentiated thyroid carcinoma without pre-ablative diagnostic 131I scintigraphy.

Differentiated thyroid cancer is treated by (near) total thyroidectomy followed by radioiodine (131I) ablation of the residual active tissue in the thyroid bed. Controversy remains concerning the use and the dose of pre-ablative diagnostic 131I scintigraphy. This study was designed to assess the efficacy of thyroid ablation by high-dose 131I without pre-ablative diagnostic 131I scintigraphy. Ninety-three patients were treated with (near) total thyroidectomy and with a high ablative dose of 131I (3700-7400 MBq). A pre-ablative 131I diagnostic scintigram was not performed. To assess the efficacy of the treatment, all patients were studied with a diagnostic 131I scintigram and with thyroglobulin plasma assays 1 year later after withdrawal of L-thyroxine for 4-6 weeks. The main criterion for a successful ablation was the absence of thyroid bed activity. An additional criterion was a thyroglobulin value of <10 μg·l−1. Successful ablation according to the main criterion was obtained in 88% of patients. Forty patients (43%) showed no neck uptake and had undetectable serum thyroglobulin. Twenty-two patients (25%) had serum thyroglobulin concentrations between 1 and 10 μg·−1. Twenty-six patients (27%) had thyroglobulin >10 μg·l−1, 19 patients showing residual thyroid uptake or metastatic lesions. We conclude that high-dose radioiodine ablation without prior diagnostic scintigraphy results in a high rate of successful ablation, preventing repeat 131I treatment.

The influence of wire localisation for non-palpable breast lesions on visualisation of the sentinel node

PurposeIn our clinic, patients with occult breast lesions are treated with a sentinel node biopsy combined with wire-guided tumour excision. The aim of this retrospective study was to determine the influence of the sequence of wire localisation and sentinel node procedure on visualisation of the sentinel node.MethodsA total of 136 patients had a wire-guided tumour excision combined with a sentinel node procedure. Sixty-six patients had guide wire localisation prior to the sentinel node procedure. Seventy patients had sentinel node visualisation before insertion of the guide wire.ResultsThe sentinel node was visualised in 41 (62%) of the patients who first underwent guide wire localisation. In the group of patients who underwent visualisation of the sentinel node before placement of the guide wire, the sentinel node was visualised in 62 (89%). This is a significant difference in visualisation (p<0.001).ConclusionThis study shows that guide wire localisation prior to the sentinel node procedure negatively influences visualisation of the sentinel node.

Captopril renography and the relevance of abnormal but bilateral identical curves in the diagnosis of renal artery stenosis.

Background Captopril renography (CR) has been shown to improve the effectiveness of renal scintigraphy in renovascular hypertension, by inhibiting angiotensin-converting enzyme. CR is particularly sensitive and specific in unilateral renal artery stenosis (RAS), but results in patients with bilateral RAS are less favourable. The aim of this study was to investigate the meaning of abnormal but identical renographic curves in the diagnosis of RAS. Patients and methods One hundred and fifty-eight patients clinically suspected for renovascular hypertension underwent CR, using 50 MBq 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3), prior to performing renal angiography. CR was performed 1 h after captopril administration. Renograms were analysed according to the consensus criteria. All patients underwent angiography, considered as the ‘gold standard’ in the detection of the presence of RAS (stenosis >50% was defined as significant). All kidneys were categorized into three groups, scintigraphically as well as angiographically: no stenosis, unilateral stenosis and bilateral stenosis. Results Out of 158 patients 100 (63%) showed a RAS on angiography (58 (37%) unilateral, 42 (26%) bilateral). The sensitivity and specificity of CR evaluated by patient was 83% and 75%, respectively. Thirty patients with completely identical curves were identified, 21 patients with normal curves and nine patients with abnormal identical curves. All but one patient showed no RAS on the angiogram. In this single patient a unilateral stenosis was found. Conclusion Identical curves on the renogram generally suggest no RAS and are probably due to intrinsic parenchymal disease.

Treatment of painful bone metastases in prostate and breast cancer patients with the therapeutic radiopharmaceutical rhenium-188-HEDP. Clinical benefit in a real-world study

Aim: Rhenium-188-HEDP (188Re-HEDP) is an effective radiopharmaceutical for the palliative treatment of osteoblastic bone metastases. However, only limited data on its routine use are available and its effect on quality of life (QoL) has not been studied. Therefore, we evaluated the clinical benefit of 188Re-HEDP in routine clinical care. Patients and methods: Prostate or breast cancer patients with painful bone metastases receiving 188Re-HEDP as a routine clinical procedure were eligible for evaluation. Clinical benefit was assessed in terms of efficacy and toxicity. Pain palliation and QoL were monitored using the visual analogue scale (VAS), corrected for opioid intake, and the EORTC QLQ-C30 Global health status/QoL-scale. Thrombocyte and leukocyte nadirs were used to assess haematological toxicity. Results: 45 and 47 patients were evaluable for pain palliation and QoL, respectively. After a single injection of 188Re-HEDP, the overall pain response rate was 69% and mean VAS-scores decreased relevantly and significantly (pAIM Rhenium-188-HEDP ((188)Re-HEDP) is an effective radiopharmaceutical for the palliative treatment of osteoblastic bone metastases. However, only limited data on its routine use are available and its effect on quality of life (QoL) has not been studied. Therefore, we evaluated the clinical benefit of (188)Re-HEDP in routine clinical care. PATIENTS AND METHODS Prostate or breast cancer patients with painful bone metastases receiving (188)Re-HEDP as a routine clinical procedure were eligible for evaluation. Clinical benefit was assessed in terms of efficacy and toxicity. Pain palliation and QoL were monitored using the visual analogue scale (VAS), corrected for opioid intake, and the EORTC QLQ-C30 Global health status/QoL-scale. Thrombocyte and leukocyte nadirs were used to assess haematological toxicity. RESULTS 45 and 47 patients were evaluable for pain palliation and QoL, respectively. After a single injection of (188)Re-HEDP, the overall pain response rate was 69% and mean VAS-scores decreased relevantly and significantly (p < 0.05). Repeated treatment resulted in similar pain response. The overall QoL response rate was 68% and mean Global health status/QoL-scores increased relevantly and significantly. Haematological side effects were mild and transient. CONCLUSION The clinically relevant response on pain and quality of life and the limited adverse events prove clinical benefit of treatment with (188)Re-HEDP and support its use in routine clinical care. Its effectiveness appears comparable to that of external beam radiotherapy.

Treatment of painful bone metastases in prostate and breast cancer patients with the therapeutic radiopharmaceutical rhenium-188-HEDP

Aim: Rhenium-188-HEDP (188Re-HEDP) is an effective radiopharmaceutical for the palliative treatment of osteoblastic bone metastases. However, only limited data on its routine use are available and its effect on quality of life (QoL) has not been studied. Therefore, we evaluated the clinical benefit of 188Re-HEDP in routine clinical care. Patients and methods: Prostate or breast cancer patients with painful bone metastases receiving 188Re-HEDP as a routine clinical procedure were eligible for evaluation. Clinical benefit was assessed in terms of efficacy and toxicity. Pain palliation and QoL were monitored using the visual analogue scale (VAS), corrected for opioid intake, and the EORTC QLQ-C30 Global health status/QoL-scale. Thrombocyte and leukocyte nadirs were used to assess haematological toxicity. Results: 45 and 47 patients were evaluable for pain palliation and QoL, respectively. After a single injection of 188Re-HEDP, the overall pain response rate was 69% and mean VAS-scores decreased relevantly and significantly (pAIM Rhenium-188-HEDP ((188)Re-HEDP) is an effective radiopharmaceutical for the palliative treatment of osteoblastic bone metastases. However, only limited data on its routine use are available and its effect on quality of life (QoL) has not been studied. Therefore, we evaluated the clinical benefit of (188)Re-HEDP in routine clinical care. PATIENTS AND METHODS Prostate or breast cancer patients with painful bone metastases receiving (188)Re-HEDP as a routine clinical procedure were eligible for evaluation. Clinical benefit was assessed in terms of efficacy and toxicity. Pain palliation and QoL were monitored using the visual analogue scale (VAS), corrected for opioid intake, and the EORTC QLQ-C30 Global health status/QoL-scale. Thrombocyte and leukocyte nadirs were used to assess haematological toxicity. RESULTS 45 and 47 patients were evaluable for pain palliation and QoL, respectively. After a single injection of (188)Re-HEDP, the overall pain response rate was 69% and mean VAS-scores decreased relevantly and significantly (p < 0.05). Repeated treatment resulted in similar pain response. The overall QoL response rate was 68% and mean Global health status/QoL-scores increased relevantly and significantly. Haematological side effects were mild and transient. CONCLUSION The clinically relevant response on pain and quality of life and the limited adverse events prove clinical benefit of treatment with (188)Re-HEDP and support its use in routine clinical care. Its effectiveness appears comparable to that of external beam radiotherapy.

Persistent Inflammation in Pulmonary Granuloma 48 Years after Talcage Pleurodesis, Detected by FDG-PET/CT

In patients with suspicion of lung malignancy, FDG PET/CT is frequently used as a diagnostic and staging imaging modality. However, false positive findings are not uncommon. We demonstrate a case with FDG-avid pulmonary nodules, mimicking lung cancer. After histopathological examination they appeared to be the result of persistent inflamed tissue, due to talcage pleurodesis, which occurred 48 years ago. We concluded that, nearly five decades after talcage pleurodesis, there can still be an ongoing inflammation reaction in the pleurae, which can be detected by FDG PET/CT.

Behandlung schmerzender Knochenmetastasen bei Patienten mit Prostata- und Brustkrebs mit dem therapeutischen Radiopharmakon Rhenium-188-HEDP

Aim: Rhenium-188-HEDP (188Re-HEDP) is an effective radiopharmaceutical for the palliative treatment of osteoblastic bone metastases. However, only limited data on its routine use are available and its effect on quality of life (QoL) has not been studied. Therefore, we evaluated the clinical benefit of 188Re-HEDP in routine clinical care. Patients and methods: Prostate or breast cancer patients with painful bone metastases receiving 188Re-HEDP as a routine clinical procedure were eligible for evaluation. Clinical benefit was assessed in terms of efficacy and toxicity. Pain palliation and QoL were monitored using the visual analogue scale (VAS), corrected for opioid intake, and the EORTC QLQ-C30 Global health status/QoL-scale. Thrombocyte and leukocyte nadirs were used to assess haematological toxicity. Results: 45 and 47 patients were evaluable for pain palliation and QoL, respectively. After a single injection of 188Re-HEDP, the overall pain response rate was 69% and mean VAS-scores decreased relevantly and significantly (pAIM Rhenium-188-HEDP ((188)Re-HEDP) is an effective radiopharmaceutical for the palliative treatment of osteoblastic bone metastases. However, only limited data on its routine use are available and its effect on quality of life (QoL) has not been studied. Therefore, we evaluated the clinical benefit of (188)Re-HEDP in routine clinical care. PATIENTS AND METHODS Prostate or breast cancer patients with painful bone metastases receiving (188)Re-HEDP as a routine clinical procedure were eligible for evaluation. Clinical benefit was assessed in terms of efficacy and toxicity. Pain palliation and QoL were monitored using the visual analogue scale (VAS), corrected for opioid intake, and the EORTC QLQ-C30 Global health status/QoL-scale. Thrombocyte and leukocyte nadirs were used to assess haematological toxicity. RESULTS 45 and 47 patients were evaluable for pain palliation and QoL, respectively. After a single injection of (188)Re-HEDP, the overall pain response rate was 69% and mean VAS-scores decreased relevantly and significantly (p < 0.05). Repeated treatment resulted in similar pain response. The overall QoL response rate was 68% and mean Global health status/QoL-scores increased relevantly and significantly. Haematological side effects were mild and transient. CONCLUSION The clinically relevant response on pain and quality of life and the limited adverse events prove clinical benefit of treatment with (188)Re-HEDP and support its use in routine clinical care. Its effectiveness appears comparable to that of external beam radiotherapy.