Influence of zoledronic acid on disseminated tumor cells in bone marrow and survival: results of a prospective clinical trial.

BACKGROUND: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients is associated with reduced clinical outcome. Bisphosphonate treatment was shown to eradicate DTC from BM in several studies. This controlled randomized open-label multi-center study aimed to investigate the influence of zoledronic acid (ZOL) on DTC and survival of breast cancer patients (Clinical Trial Registration Number: NCT00172068). METHODS: Patients with primary breast cancer and DTC-positive bone marrow were randomized to treatment with ZOL plus adjuvant systemic therapy (n = 40) or adjuvant systemic therapy alone (n = 46) between 03/2002 and 12/2004. DTC were identified by immunocytochemistry using the pancytokeratin antibody A45B/B3 and by cytomorphology. The change in DTC numbers at 12 months and 24 months versus baseline, as well as patient outcomes were evaluated. RESULTS: 86 patients could be included into survival analysis (median follow-up: 88 months, range: 8-108 mths). Patients in the control group were more likely to die during follow-up than those in the ZOL-group (11% vs. 2%, p = 0.106). 15% of patients in the control group presented with relapse whereas only 8% of ZOL group patients developed metastatic or recurrent disease during follow-up (p = 0.205). At 24 months, 16% of patients from the control group were still DTC positive, whereas all patients treated with ZOL became DTC negative (p = 0.032). Patients presenting with persistent DTC 12 months after diagnosis had significantly shorter overall survival (p = 0.011). CONCLUSIONS: Bisphosphonate therapy contributes to eradication of disseminated tumor cells. The positive influence of bisphosphonates on survival in the adjuvant setting may be due to their effects on DTC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00172068 [Zoledronic Acid in the Treatment of Breast Cancer With Minimal Residual Disease in the Bone Marrow (MRD-1)].

[Complete remission of multiple brain metastases of non-small cell lung cancer induced by gefitinib monotherapy]. / Komplette Remission multifokaler zerebraler Metastasen bei chemotherapierefraktärem NSCLC durch Monotherapie mit Gefitinib.

BACKGROUND: While the activity of tyrosine kinase inhibitors as the first line treatment for primary tumors in patients with stage IV non-small cell lung cancer and a positive EGF receptor mutation is well known, little data on the efficacy in controlling cerebral metastases are available. CASE REPORT AND RESULTS: A 43-year-old woman was diagnosed with non-small cell lung cancer with cerebral and hepatic metastases. Emergency radiation therapy was initiated at the time of diagnosis due to superior vena cava syndrome. However, after she failed to respond to this therapy and in light of a positive EGF receptor mutation, gefitinib was added at a dose of 250 mg/day while continuing radiation to the primary lesion and cervical lymph nodes. She showed a rapid clinical and radiologic response with complete remission of the cerebral metastases 6 weeks after starting gefitinib. No severe toxicity was observed. CONCLUSION: This case demonstrates that gefitinib can be given during radiation treatment without significant toxicity. Furthermore, complete remission of cerebral metastases can be achieved with tyrosine kinase inhibitor monotherapy.

Successful treatment of paraneoplastic hypercalcemia in a patient with giant condyloma acuminatum: a case report.

INTRODUCTION: While paraneoplastic syndromes in patients with malignant and metastasizing tumors are common, they are rarely associated with skin tumors showing predominantly local growth patterns. This case report relates to a patient with giant condyloma acuminatum, also called Buschke-Löwenstein tumor, with paraneoplastic hypercalcemia, who was successfully treated with conservative treatment. CASE PRESENTATION: The patient in question is a 48-year-old German man with a giant periscrotal tumor. Before and during the therapy, two episodes of symptomatic hypercalcemia occurred, which were successfully treated by bisphosphonates, intravenous fluids and diuretics. No evidence of lytic bone affection was found. CONCLUSIONS: Paraneoplastic hypercalcemia may occur in patients who have a Buschke-Löwenstein tumor. For patients, where surgery is not an option, established medical therapies like bisphosphonates may be useful in addition to diuretics and infusions.

Painful spinal cord compression as a complication of extramedullary hematopoiesis associated with beta-thalassemia intermedia.

BACKGROUND: Spinal cord compression due to extramedullary hematopoiesis (EMH) is a rare manifestation of thalassemia. General therapeutic recommendations do not exist. CASE REPORT: We report a 23 year old male with beta-thalassemia intermedia and back pain resistant to analgetic medication. Multiple extradural mass lesions on MRI of the lumbar spine were identified. Hypertransfusion was initiated with no relief of symptoms. Low dose irradiation with 20 Gy had to be added to achieve adaequate response. RESULT: With the combination of transfusion therapy and irradiation a rapid and long-lasting relief of symptoms was achieved. 12 month post irradiation the patient is free of pain and neurological symptoms. CONCLUSION: Clinical awareness of this phenomenon and knowledge of the available treatment option is essential for successful outcome. In treatment refractory symptoms irradiation could successfully contribute to a rapid therapeutic response.

Molecular targeting of the lymphovascular system for imaging and therapy.

Progress toward targeting cancer cells is a multi-disciplinary endeavor. In addition to the surgical and oncology specialties, radiologists collaborate with mathematicians, computer scientists, and physicists, in a constant effort to incrementally improve upon the current imaging modalities. Recently, radiologists have formed collaborations with molecular biologists and chemists in order to develop molecular agents that target cancer cells via receptor-substrate or specific physiochemical interactions. In this review, we summarize selected efforts toward molecular targeting of the lymphovascular system. Standard imaging modalities, positron emission tomography, single photon emission tomography, and ultrasound, are reviewed as well as, the targeted introduction of substances for endolymphatic therapy. We also review the current status of sentinel lymph node mapping with radiocolloids and the application of molecular targeting for the development of a radiopharmaceutical specifically designed for sentinel lymph node mapping.