Radionuclide therapy of painful bone metastases--a comparative study between consecutive radionuclide infusions, combination with chemotherapy, and radionuclide infusions alone: an in vivo comparison of their effectiveness.

Radionuclides have been long used for the palliation of skeletal-related metastatic pain. They are almost invariably used as the last resource for pain palliation. Their use as single agents with dose escalations, in combination with biphosphonates or chemotherapy is well known in the peer-reviewed literature; however, little is known about the combination between different agents. In our study, we used consecutive administration of 2 different radionuclides such as (186)Re-1,1-hydroxyethylidenediphosphonate ((186)Re-HEDP) and (89)Strontium Chloride ((89)Sr-Cl) separated by adequate period of time to allow bone marrow recovery in patients with high chance of bone pain relapse and compared it with (89)Sr-Cl and chemotherapy group and (186)Re-HEDP with bisphosphonates. The end result was that treatment with consecutive radionuclides was much more effective and safe than the other 2 groups.

Neuroendocrine tumors: a focus on liver metastatic lesions.

Transhepatic radionuclide infusion has been introduced as a new treatment approach for unresectable liver neuroendocrine metastatic lesions with the prerequisite of a positive In-111 Pentetreotide (Octreoscan). Patients with multiple liver neuroendocrine metastases can be locally treated after selective hepatic artery catheterization and infusion of radiolabeled somatostatin analogs, and in case of extra-hepatic secondary spread, after simple i.v. application. According to the world wide references, the average dose per session to each patient is 6.3 ± 0.3 GBq (∼160-180 mCi) of In-111-DTPA-Phe1-Pentetreotide, 10- to 12-fold in total, administered monthly or of 4.1 ± 0.2 GBq (∼105-116 mCi) of Y-90 DOTA TOC, threefold in total, or of 7.0 ± 0.4 GBq (∼178-200 mCi) of Lu-177 DOTA TATE, fourfold to sixfold in total (the choice of which being based on the tumor size, assessed by CT or MRI). Follow-up at monthly intervals has to be performed by means of ultrasonography (US). Treatment response has to be assessed according to the WHO criteria (RECIST or SWOG).

Predictive implications of bone turnover markers after palliative treatment with (186)Re-HEDP in hormone-refractory prostate cancer patients with painful osseous metastases.

PURPOSE: To prospectively evaluate the predictive value of various bone formation and resorption markers in patients with bone metastases from prostate cancer after palliative treatment with (186)Re-1,1-hydroxyethylidene diphosphonate ((186)Re-HEDP). METHODS: Included in the study were 36 men with prostate cancer, suffering from painful osseous metastases and treated with (186)Re-HEDP. None had received any treatment that would have interfered with bone metabolism before (186)Re-HEDP treatment or throughout the follow-up period. For each patient, pretreatment and posttreatment serum levels of osteocalcin (OC), bone alkaline phosphatase (BALP), aminoterminal (PINP) and carboxyterminal (PICP) propeptides of type I collagen, amino-terminal (NTx) and carboxyterminal (CTx) telopeptides of type I collagen and their combinations were compared with the level and duration of pain response to radionuclide treatment. RESULTS: Pain response was correlated only with pretreatment NuTaux/PINP, PICP/PINP and NTx/CTx ratios and posttreatment decrease in baseline NTx and PICP values (p = 0.0025-0.035). According to multivariate and ROC analyses, the best marker-derived predictors of better and longer duration of response to (186)Re-HEDP treatment were a posttreatment decrease in NTx of > or = 20% (RR = 3.44, p = 0.0005) and a pretreatment NTx/PINP ratio of > or = 1.2 (RR = 3.04, p = 0.036) CONCLUSION: NTx, a potent collagenous marker of bone resorption, along with the novel NTx/PINP ratio provide useful cut-off values for identifying a group of patients suffering from painful osseous metastases from hormone-refractory prostatic carcinoma who do not respond to palliative treatment with (186)Re-HEDP. This information could help avoid an inefficient and expensive radionuclide treatment. Also, in the cohort of patients who will eventually undergo such treatment, the medium-term posttreatment changes in NTx offer valuable predictive information regarding long-term palliative response.

Clinical and imaging correlations of bone turnover markers in prostate cancer patients with bone only metastases.

OBJECTIVES: To correlate serum levels of bone markers with pain levels and extent of skeletal disease (EOD), in patients suffering from prostate cancer with bone only metastases. METHODS: Thirty-six males with hormone-refractory prostate carcinoma, bone only metastases and no history of therapies, drugs, or diseases that affect bone metabolism were studied. Karnofsky performance status, pain scoring, EOD, osteocalcin (OC), prostate-specific antigen, bone alkaline phosphatase amino-terminal and carboxy-terminal propeptides and telopeptides of type I collagen were analysed. Twenty-four healthy controls of the same age were also established. RESULTS: With only the exception of OC, bone marker values of patients were significantly increased compared with the upper reference limits (P<0.0001 for bone alkaline phosphatase and amino-terminal telopeptide of type I collagen, 0.012 for amino-terminal propeptide of type I collagen, 0.0023 for carboxy-terminal propeptide of type I collagen, and 0.04 for carboxy-terminal telopeptide of type I collagen). All bone markers and prostate-specific antigen also showed significant paired correlations (P < or = 0.019) and linear increases with advancing EOD (P < or = 0.032). Finally, none of the measured markers correlated significantly with pain levels. CONCLUSION: Bone markers are remarkably elevated in the serum of prostate cancer patients with metastatic bone disease and correlate with EOD. Paired correlations also suggest an accelerated but proportional (coupled) bone metabolism.

Management of metastatic bone pain with repeated doses of rhenium 186-HEDP in patients under therapy with zoledronic acid: a safe and additively effective practice.

PURPOSE: The aim of this study was to compare pain response and hematologic toxicity between single and multiple therapies with (186)Re-HEDP under zoledronic acid in patients suffering from painful osseous metastases from prostate or breast cancer. MATERIALS AND METHODS: Forty-five (45) patients received multiple therapies of (186)Re-HEDP (n = 77), under a stable regimen of analgesics and zoledronic acid, far off other therapeutic manipulations, and with no extraosseous disease progression. Hematologic status and pain indices were followed up regularly. RESULTS: Evaluable patients (n = 12), received 31 (186)Re-HEDP therapies. After the first treatment with (186)Re-HEDP, the mean percentile decrease for hemoglobin was 4.7%, for white blood cells was 21.4%, and for platelets was 12%. After multiple therapies, the respective declines were 7.0%, 16.0%, and 23.4%. With respect to baseline blood counts, only thrombocytes showed a tendency for greater decrease after repeated treatments, yet not of clinical significance. Favorable clinical response occurred after the first therapy in 10 of 12 patients (83.3%), after multiple doses in 15 of 19 (78.9%), and overall in 25 of 31 (80.6%) of (186)Re-HEDP therapies. Significant post-therapy improvement in pain indices was observed in all cases, regardless of the number of therapeutic doses. CONCLUSIONS: Retreatments with (186)Re-HEDP under zoledronic acid provide continuing effectiveness in metastatic bone pain and are safe enough, if an acceptable baseline hematologic status exists.

Severe dopaminergic pathways damage in a case of chronic toluene abuse.

INTRODUCTION: Toluene toxicity primarily affects central nervous system white matter, causing a characteristic brain MRI pattern. CASE REPORT: A toluene addicted man, after an abstinence period and a treatment with neuroleptics, presented with severe worsening of preexisting generalized tremor, opsoclonus, dysarthria, gait inability, jerky tendon reflexes and behaviour disorders. Magnetic resonance imaging showed mild leukoencephalopathy and hypointensities in deep gray matter nuclei. The DaT-scan revealed a decrease in presynaptic dopamine reuptake. CONCLUSION: Clinical and neuroradiological findings and the possible sensitivity to neuroleptics indicate dopaminergic impairment. Our case suggests that chronic toluene abuse causes presynaptic dopaminergic depletion.

Selective hepatic arterial infusion of In-111-DTPA-Phe1-octreotide in neuroendocrine liver metastases.

PURPOSE: The aim of this study is to evaluate the effectiveness of (111)In-DTPA-Phe(1)-octreotide infusions after selective catheterization of the hepatic artery in inoperable metastasised liver, sst(2) receptor-positive neuroendocrine tumours due to the effect of (111)In Auger electron emission, minimising in parallel the toxicity of non-target tissue. METHODS: The average dose per session administered monthly to each patient (17 cases in total) was 6.3+/-2.3 GBq. Repetitions did not exceed 12-fold, except in one case (15 sessions). Response assessment was classified according to the Response Evaluating Criteria in Solid Tumours. CT/MRI scans were performed as baseline before, during and after the end of treatment, and monthly ultrasound images for follow-up measurements. Toxicity (World Health Organization criteria) was measured using blood and urine tests of renal, hepatic and bone marrow function. RESULTS: Complete response was achieved in one (5.9%) patient and partial in eight (47.0%), and disease stabilization in 3 (17.7%) patients; five (29.4%) did not respond. A 32-month median survival time was estimated in 12 (70.5%). Nine of these 12 surviving had a mean target diameter shrinkage from 144+/-81 to 60+/-59 mm. Grade 1 erythro-, leuko- and thrombo-cytopenia occurred in three (17.6%) cases. CONCLUSION: In unresectable metastatic liver lesions positive for somatostatin receptors repeated, transhepatic high doses of (111)In-DTPA-Phe(1)-octreotide show an effective therapeutic outcome. Given the locoregional modality character of the administration technique plus the extremely short range of (111)In Auger and internal conversion electrons emission, no nephro-, liver- or myelo-toxicity has so far been observed.

Patient-specific dosimetry calculations using mathematic models of different anatomic sizes during therapy with 111In-DTPA-D-Phe1-octreotide infusions after catheterization of the hepatic artery.

UNLABELLED: The aim of the study was to provide dosimetric data on intrahepatic (111)In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe(1)-octreotide therapy for neuroendocrine tumors with overexpression of somatostatin receptors. METHODS: A dosimetric protocol was designed to estimate the absorbed dose to the tumor and healthy tissue in a course of 48 treatments for 12 patients, who received a mean activity of 5.4 +/- 1.7 GBq per session. The patient-specific dosimetry calculations, based on quantitative biplanar whole-body scintigrams, were performed using a Monte Carlo simulation program for 3 male and 3 female mathematic models of different anatomic sizes. Thirty minutes and 2, 6, 24, and 48 h after the radionuclide infusion, blood-sample data were collected for estimation of the red marrow radiation burden. RESULTS: The mean absorbed doses per administered activity (mGy/MBq) by the critical organs liver, spleen, kidneys, bladder wall, and bone marrow were 0.14 +/- 0.04, 1.4 +/- 0.6, 0.41 +/- 0.08, 0.094 +/- 0.013, and (3.5 +/- 0.8) x 10(-3), respectively; the tumor absorbed dose ranged from 2.2 to 19.6 mGy/MBq, strongly depending on the lesion size and tissue type. CONCLUSION: The results of the present study quantitatively confirm the therapeutic efficacy of transhepatic administration; the tumor-to-healthy-tissue uptake ratio was enhanced, compared with the results after antecubital infusions. Planning of treatment was also optimized by use of the patient-specific dosimetric protocol.