A phase I study of combined docetaxel and repeated high activity 186Re-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial).

PURPOSE: Bone-seeking radiopharmaceuticals have palliative benefit in castration-resistant prostate cancer (CRPC) metastatic to bone. Recent studies have shown improvement of survival and quality of life when radiopharmaceuticals were given repeatedly or in combination with chemotherapy. We designed a phase I study combining docetaxel and (186)Re-labelled hydroxyethylidene diphosphonate (HEDP) in men with CRPC and bone metastases to evaluate toxicity. METHODS: A dose escalation schedule was designed consisting of four dose levels with a standard dosage of docetaxel (75 mg/m(2) 3-weekly). (186)Re-HEDP was given in increasing activities (1,250 MBq up to 2,500 MBq) after the third and sixth cycle of docetaxel. Dose limiting toxicity (DLT) was defined as any grade 4 toxicity lasting more than 7 days or any grade 3 toxicity that did not recover within 10 days. Three patients were planned for each dose level expanding to six if a DLT occurred. RESULTS: Fourteen patients were recruited with a median age of 64.6 years. One DLT, grade 3 thrombocytopenia lasting >10 days, occurred at dose level 3 leading to expansion of this group to six. One of these patients had an episode of acute renal failure which resolved. Because of production problems of (186)Re-HEDP dose level 4 was not started. CONCLUSION: Combined therapy with docetaxel and (186)Re-HEDP is generally well tolerated in patients with CRPC metastatic to bone. We will conduct a randomized phase II study using three cycles of docetaxel 75 mg/m(2) 3-weekly followed by (188)Re-HEDP 40 MBq/kg body weight, followed by another three cycles of docetaxel 75 mg/m(2), followed by (188)Re-HEDP 20 MBq/kg body weight.

CT and 18F-FDG PET for noninvasive detection of splenic involvement in patients with malignant lymphoma.

OBJECTIVE: The purpose of this study was to determine the sensitivity and specificity of (18)F-FDG PET, CT, and combined PET/CT in the detection of splenic involvement at initial staging of lymphoma. MATERIALS AND METHODS: A retrospective longitudinal analysis was performed on the records of 111 patients with proven lymphoma who had undergone PET and CT before and after treatment. CT scans were evaluated independently by two radiologists, and PET scans by two nuclear medicine physicians. Abnormal CT findings were defined as low-attenuation nodules or a splenic index greater than 725 cm(3) (> 2 SDs above the mean in 100 controls). An abnormal PET finding was defined as splenic uptake greater than hepatic uptake. True splenic involvement was defined retrospectively on the basis of the treatment response assessed with criteria revised in the International Harmonization Project on lymphoma. Observer agreement and sensitivity and specificity values were calculated. RESULTS: Observer agreement for CT splenic index and PET findings was good. For initial splenic staging, the sensitivity and specificity of CT, PET, and PET/CT were 91% and 96%, 75% and 99%, and 100% and 95%. CONCLUSION: For initial staging of splenic involvement in malignant lymphoma, the sensitivity and specificity of PET/CT can reach 100% and 95%. The sensitivity of the combined approach is higher than that of either technique alone.

[FDG-PET/CT in staging of breast carcinoma: use in tumour stage III and locoregional recurrent breast carcinoma]. / FDG-PET/CT bij stadiëring van mammacarcinoom: toepassing bij tumorstadium III en locoregionaal recidief.

In stage III breast carcinoma, metastasized disease needs to be determined. In the past, conventional imaging by liver ultrasound, chest X-ray and bone scintigraphy was the work-up of choice. Recently, FDG-PET/CT was found to have additional value, but clinicians are hesitant to introduce this technique. We present three patients in whom FDG-PET/CT was applied. A 61-year-old woman with stage III breast carcinoma after conventional work-up was upstaged to stage IV breast carcinoma by FDG-PET/CT, upon which her treatment was changed. A 55-year-old woman suspected of stage IV breast carcinoma after conventional imaging was downstaged to stage III after FDG-PET/CT. Her treatment was changed as well. In a 78-year-old woman with recurrent breast carcinoma, the diagnostic certainty of stage III breast carcinoma was increased by FDG-PET/CT. We conclude that FDG-PET/CT is valuable for adequately diagnosing metastases in patients with stage III breast carcinoma and can replace conventional imaging.

On the added value of baseline FDG-PET in malignant lymphoma.

PURPOSE: The added value of baseline positron emission tomography (PET) scans in therapy evaluation in malignant lymphoma is unclear. In guidelines, baseline PET is recommended but not mandatory except in lymphoma types with variable fluoro-D-glucose uptake. The aim of the present study was to test the hypothesis that adding baseline PET information decreases false positive readings with posttreatment PET and improves observer agreement. METHODS: Forty-four patients (mean age 56 years, standard deviation 14) with malignant lymphoma were included. Two nuclear medicine physicians retrospectively and independently evaluated the posttreatment PET, 3 weeks later followed by paired reading of baseline and posttreatment PET. For each PET, 22 regions were classified as positive, negative, or equivocal, resulting in an overall PET score of positive, unclear, or negative. In case of discrepancies, consensus was reached. RESULTS: Addition of baseline to posttreatment PET evaluation affected the classification of metabolic response in 34% of malignant lymphoma patients treated with first-line chemotherapy. In one out of seven patients, addition of the baseline PET lead to opposite conclusions (95% confidence interval 4-14). False positivity was reduced by adding the baseline scan information, but the effect on false negativity was similar. In addition, the amount of unclear classifications halved after paired reading. Observer agreement did not improve upon adding the baseline PET data. CONCLUSION: Without any other clinical information, pretreatment PET facilitates changes the interpretation of a posttreatment PET in a third of the patients, resulting in both upgrading and downgrading of the posttreatment situation of a malignant lymphoma patient. If these results are confirmed for PET-computed tomography systems, they favor the addition of baseline PET to the current work-up of patients with malignant lymphoma.