Long-term survival of breast cancer patients with brain metastases: subanalysis of the BMBC registry.

BACKGROUND: Up to 30% of metastatic breast cancer (BC) patients develop brain metastases (BM). Prognosis of patients with BM is poor and long-term survival is rare. Identification of factors associated with long-term survival is important for improving treatment modalities. PATIENTS AND METHODS: A total of 2889 patients of the national registry for BM in BC (BMBC) were available for this analysis. Long-term survival was defined as overall survival (OS) in the upper third of the failure curve resulting in a cut-off of 15 months. A total of 887 patients were categorized as long-term survivors. RESULTS: Long-term survivors compared to other patients were younger at BC and BM diagnosis (median 48 versus 54 years and 53 versus 59 years), more often had HER2-positive tumors (59.1% versus 36.3%), less frequently luminal-like (29.1% versus 35.7%) or triple-negative breast cancer (TNBC) (11.9% versus 28.1%), showed better Eastern Cooperative Oncology Group (ECOG) performance status (PS) at the time of BM diagnosis (ECOG 0-1, 76.9% versus 51.0%), higher pathological complete remission rates after neoadjuvant chemotherapy (21.6% versus 13.7%) and lower number of BM (n = 1, BM 40.9% versus 25.4%; n = 2-3, BM 26.5% versus 26.7%; n ≥4, BM 32.6% versus 47.9%) (P < 0.001). Long-term survivors had leptomeningeal metastases (10.4% versus 17.5%) and extracranial metastases (ECM, 73.6% versus 82.5%) less frequently, and asymptomatic BM more often at the time of BM diagnosis (26.5% versus 20.1%), (P < 0.001). Median OS in long-term survivors was about two times higher than the cut-off of 15 months: 30.9 months [interquartile range (IQR) 30.3] overall, 33.9 months (IQR 37.1) in HER2-positive, 26.9 months (IQR 22.0) in luminal-like and 26.5 months (IQR 18.2) in TNBC patients. CONCLUSIONS: In our analysis, long-term survival of BC patients with BM was associated with better ECOG PS, younger age, HER2-positive subtype, lower number of BM and less extended visceral metastases. Patients with these clinical features might be more eligible for extended local brain and systemic treatment.

Characteristics of patients with brain metastases from human epidermal growth factor receptor 2-positive breast cancer: subanalysis of Brain Metastases in Breast Cancer Registry.

BACKGROUND: Up to 40% of patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer develop brain metastases (BMs). Understanding of clinical features of these patients with HER2-positive breast cancer and BMs is vital. PATIENTS AND METHODS: A total of 2948 patients from the Brain Metastases in Breast Cancer registry were available for this analysis, of whom 1311 had primary tumors with the HER2-positive subtype. RESULTS: Patients with HER2-positive breast cancer and BMs were-when compared with HER2-negative patients-slightly younger at the time of breast cancer and BM diagnosis, had a higher pathologic complete response rate after neoadjuvant chemotherapy and a higher tumor grade. Furthermore, extracranial metastases at the time of BM diagnosis were less common in HER2-positive patients, when compared with HER2-negative patients. HER2-positive patients had more often BMs in the posterior fossa, but less commonly leptomeningeal metastases. The median overall survival (OS) in all HER2-positive patients was 13.2 months (95% confidence interval 11.4-14.4). The following factors were associated with shorter OS (multivariate analysis): older age at BM diagnosis [≥60 versus <60 years: hazard ratio (HR) 1.63, P < 0.001], lower Eastern Cooperative Oncology Group status (2-4 versus 0-1: HR 1.59, P < 0.001), higher number of BMs (2-3 versus 1: HR 1.30, P = 0.082; ≥4 versus 1: HR 1.51, P = 0.004; global P = 0.015), BMs in the fossa anterior (HR 1.71, P < 0.001), leptomeningeal metastases (HR 1.63, P = 0.012), symptomatic BMs at diagnosis (HR 1.35, P = 0.033) and extracranial metastases at diagnosis of BMs (HR 1.43, P = 0.020). The application of targeted therapy after the BM diagnosis (HR 0.62, P < 0.001) was associated with longer OS. HER2-positive/hormone receptor-positive patients showed longer OS than HER2-positive/hormone receptor-negative patients (median 14.3 versus 10.9 months; HR 0.86, P = 0.03), but no differences in progression-free survival were seen between both groups. CONCLUSIONS: We identified factors associated with the prognosis of HER2-positive patients with BMs. Further research is needed to understand the factors determining the longer survival of HER2-positive/hormone receptor-positive patients.

Treatment and outcomes of patients in the Brain Metastases in Breast Cancer Network Registry.

BACKGROUND: Brain metastases (BMs) have a major impact on life expectancy and quality of life for many breast cancer patients. Knowledge about treatment patterns and outcomes is limited. METHODS: We analysed clinical data of 1712 patients diagnosed with BMs from breast cancer between January 2000 and December 2016 at 80 institutions. RESULTS: Median age at diagnosis of BMs was 56 years (22-90 years). About 47.8% (n = 732) of patients had HER2-positive, 21.4% (n = 328) had triple-negative and 30.8% (n = 471) had hormone receptor (HR)-positive, HER2-negative (luminal-like) primary tumours. The proportion of patients with HER2-positive BMs decreased comparing the years 2000-2009 with 2010-2015 (51%-44%), whereas the percentage of patients with luminal-like tumours increased (28%-34%; p = 0.0331). Patients with BMs in the posterior fossa were more often HER2 positive (n = 169/314, 53.8%) than those diagnosed with triple-negative (n = 65/314, 20.7%) or luminal-like primary breast cancer (n = 80/314, 25.5%), (p < 0.0001). Median overall survival (OS) time after development of BMs for the overall cohort was 7.4 months (95% confidence interval [CI]: 6.7-8.0 months). One-year survival rate was 37.7% (95% CI: 35.2-40.1). Patients with HER2-positive tumours had the longest median OS of 11.6 months (95% CI: 10.0-13.4) compared with 5.9 months (95% CI: 5.0-7.2) for patients with luminal-like and 4.6 months (95% CI: 3.9-5.4) for patients with triple-negative tumours. Patients with HER2-positive tumours who received anti-HER2 treatment had longer median OS than those without (17.1 months versus 7.2 months, p < 0.0001). CONCLUSIONS: Prognosis of patients after developing BMs varies significantly according to the subtype. The outcome in this cohort is similarly poor in triple-negative and HR-positive/HER2-negative patients. Our results underline the high medical need for improvement of treatment and prevention strategies for BMs in breast cancer patients.

RXLR effector diversity in Phytophthora infestans isolates determines recognition by potato resistance proteins; the case study AVR1 and R1.

Late blight disease caused by the plant pathogenic oomycete pathogen Phytophthora infestans is one of the most limiting factors in potato production. P. infestans is able to overcome introgressed late blight resistance by adaptation of effector genes. AVR1 is an RXLR effector that triggers immune responses when recognized by the potato resistance protein R1. P. infestans isolates avirulent on R1 plants were found to have AVR1 variants that are recognized by R1. Virulent isolates though, lack AVR1 but do contain a close homologue of AVR1, named A-L, of which all variants escape recognition by R1. Co-expression of AVR1 and R1 in Nicotiana benthamiana results in a hypersensitive response (HR). In contrast, HR is not activated when A-L is co-expressed with R1. AVR1 and A-L are highly similar in structure. They share two W motifs and one Y motif in the C-terminal part but differ in the T-region, a 38 amino acid extension at the carboxyl-terminal tail of AVR1 lacking in A-L. To pinpoint what determines R1-mediated recognition of AVR1 we tested elicitor activity of AVR1 and A-L chimeric and deletion constructs by co-expression with R1. The T-region is important as it enables R1-mediated recognition of A-L, not only when fused to A-L but also via trans-complementation. Yet, AVR1 lacking the T-region is still active as an elicitor of HR, but this activity is lost when certain motifs are swapped with A-L. These data show that A-L circumvents R1 recognition not only because it lacks the T-region, but also because of differences in the conserved C-terminal effector motifs.

Follow-up Reality for Breast Cancer Patients - Standardised Survey of Patients and Physicians and Analysis of Treatment Data.

Introduction: Currently, about 360 000 breast cancer patients who could, after completion of their primary therapy, take advantage of follow-up options are living in Germany. Up to now very little is known about the extent to which the available options are used and as to how the follow-up reality is experienced and evaluated. Thus, an explorative examination among the patients and their physicians was undertaken. Patients and Methods: All patients who underwent surgery in a certified breast centre between 2007 and 2013 received a standardised questionnaire; at the same time the physicians responsible for the follow-up were invited to answer a standardised questionnaire. Results: 920 patients (response rate: 61 %) with a median age of 65 years (32-95) could be analysed. 99 % of the participants stated that they regularly attended follow-ups. The personal contact with the physician (mean value: 4.4) and the reassurance that the cancer disease had not recurred (mean value: 4.5) were described on a scale of 0 to 5 to be two of the most important factors of the follow-up. Deficits were expressed with regard to psychosocial care (70 %) and the perception and treatment of physical complaints (55 %). In addition, 105 physicians returned completed questionnaires (response rate: 12 %). For asymptomatic patients the physicians performed the following examinations most frequently: anamnesis (92 %), physical examination (87 %) as well as laboratory tests (63 %) and tumour marker determinations (40 %). Conclusion: On the whole it became clear that the vast majority of the patients took advantage of the follow-up options. From the patient's perspective the importance of the follow-up lies in contact to the physician and the comforting assurance that the breast cancer has not relapsed. Deficits are seen in the psychosocial care and the perception and treatment of physical impairments. Not recommended examinations were employed by a significant proportion of the surveyed physicians.

[Immunoglobulin substitution in patients with indolent non-Hodgkin's lymphoma]. / Immunglobulin-Substitution bei Patienten mit indolenten Non-Hodgkin-Lymphomen.

BACKGROUND: Infections are major complications in chronic lymphoproliferative disorders, among them indolent non-Hodgkin's lymphoma (iNHL) including chronic lymphocytic leukemia, follicular lymphoma and multiple myeloma.We report on a retrospective cohort analysis of outpatients with indolent non-Hodgkin's lymphoma who were treated in an oncology / hematology group practice and received intravenous polyvalent immunoglobulin G (IVIG) as supportive care. The aim was to describe the treated iNHL population, the course of therapy and the effects of IVIG administrations on the levels of immunoglobulin G (IgG), the incidence of infections and the survival time. PATIENTS AND METHOD: 57 patients with secondary iNHL antibody deficiencies (n = 46) or IgG subclass deficiencies (n = 11) who received IVIG substitution were included. Patients received median 11 IVIG doses with a mean dose of 28 g over a period of median 9.5 months. RESULTS: Mean IgG levels increased with IVIG substitution at about twice and then remained within the normal range. The incidence of infections decreased in 46 % of treated patients. Effects on survival could not be observed. Median overall survival was in the group of substituted patients 124 months (range 7-124), the control group had a median survival time of 96 months (range 3-129) (p = 0.537). CONCLUSION: IgG levels should be reviewed during IVIG substitution on a regular basis and dosage and intervals should be adjusted individually.

The impact of allogeneic stem cell transplantation on the natural course of poor-risk chronic lymphocytic leukemia as defined by the EBMT consensus criteria: a retrospective donor versus no donor comparison.

BACKGROUND: In a single-center retrospective donor versus no-donor comparison, we investigated if allogeneic stem cell transplantation (alloSCT) can improve the dismal course of poor-risk chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: All patients with CLL who were referred for evaluation of alloSCT within a 7-year time frame and had a donor search indication according to the EBMT criteria or because of Richter's transformation were included. Patients for whom a matched donor could be found within 3 months (matches) were compared with patients without such a donor (controls). Primary end point was overall survival measured from the 3-month landmark after search initiation. RESULTS: Of 105 patients with donor search, 97 (matches 83; controls 14) were assessable at the 3-month landmark. Matches and controls were comparable for age, gender, time from diagnosis, number of previous regimens, and remission status. Disregarding if alloSCT was actually carried out or not, survival from the 3-month landmark was significantly better in matches versus controls [hazard ratio 0.38, 95% confidence interval (CI) 0.17-0.85; P = 0.014]. The survival benefit of matches remained significant on multivariate analysis. CONCLUSION: This study provides first comparative evidence that alloSCT may have the potential to improve the natural course of poor-risk CLL as defined by the EBMT criteria.

Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): a multicenter study.

Myelodysplastic syndromes (MDS) with del(5q) are considered to have a benign course of the disease. In order to address the issue of the propensity of those patients to progress to acute myeloid leukemia (AML), data on 381 untreated patients with MDS and del(5q) characterized by low or intermediate I International Prognostic Scoring System (IPSS) risk score were collected from nine centers and registries. Median survival of the entire group was 74 months. Transfusion-dependent patients had a median survival of 44 months vs 97 months for transfusion-independent patients (P<0.0001). Transfusion need at diagnosis was the most important patient characteristic for survival. Of the 381 patients, 48 (12.6%) progressed to AML. The cumulative progression rate calculated using the Kaplan-Meier method was 4.9% at 2 years and 17.6% at 5 years. Factors associated with the risk of AML transformation were high-risk World Health Organization adapted Prognostic Scoring System (WPSS) score, marrow blast count >5% and red-cell transfusion dependency at diagnosis. In conclusion, patients with MDS and del(5q) are facing a considerable risk of AML transformation. More detailed cytogenetic and molecular studies may help to identify the patients at risk of progression.

Evaluation of psychosocial distress in patients treated in a community-based oncology group practice in Germany.

BACKGROUND: Systematic evaluation of psychosocial distress in oncology outpatients is an important issue. We assessed feasibility and benefit of standardized routine screening using the Distress Thermometer (DT) and Problem List (PL) in all patients of our community-based hematooncology group practice. PATIENTS AND METHODS: One thousand four hundred forty-six patients were screened between July 2008 and September 2008. Five hundred randomly selected patients were sent a feedback form. RESULTS: The average distress level was 4.7, with 37% indicating a distress level >5. Patients with nonmalignant diseases (81% autoimmune diseases or hereditary hemochromatosis) showed the highest distress level of 5.2. Most distressed were patients who just learned about relapse or metastases (6.4), patients receiving best supportive care (5.4) and patients receiving adjuvant antihormonal therapy (5.4). Ninety-seven percent of patients appreciated to speak to their doctor about their distress. Fifty-six percent felt better than usual after this consultation. CONCLUSION: DT and PL are feasible instruments to measure distress in hematooncology outpatients receiving routine care. DT and PL are able to improve doctor-patient communication and thus should be implemented in routine patient care. The study shows that distress is distributed differently between individuals, disease groups and treatment phases.

The impact of new treatment options for advanced colorectal cancer on routine care: results of a retrospective analysis of 206 consecutive patients treated in a community-based oncology group practice in Germany.

Due to necessary selection criteria, the results obtained in clinical trials may not reflect the actual impact of current treatment options for unselected general populations. We analysed the treatment modalities and the outcome in 206 consecutive patients with advanced colorectal cancer who started treatment between 1/1999 and 11/2004. The median age of this cohort was 66 years (range 30-87) and 39 patients (19%) were ≥ 75 years old. First-line treatment consisted of low-dose bolus 5-fluorouracil and folinic acid regimens in 68 patients (33%), weekly 24-h 5-fluorouracil infusion and folinic acid in 36 patients (17%), weekly 24-h 5-fluorouracil infusion plus oxaliplatin or irinotecan in 60 patients (29%), capecitabine regimens in 22 patients (11%), monotherapy with oxaliplatin or irinotecan in six patients (3%) and other regimens in 14 patients (7%). A total of 166 patients (81%) received a second-line treatment and third-line chemotherapy was given to 122/206 patients (59%). With a minimum follow-up of 18 months, the median survival of the cohort is 21 months (range 1-85) and 17 months (range 3-57) for patients ≥ 75 years. We conclude that the increased survival seen in prospective studies can be transferred to routine care for unselected patients with advanced colorectal cancer.

[Lymphomas: new therapeutic options]. / Lymphomverdacht. Wie gehen Sie vor, welche Chancen hat ihr Patient?

Malignant lymphomas are differentiated clinically, morphologically and molecular-biologically, into aggressive (formerly high-grade malignant) and indolent (formerly low-grade malignant) lymphomas. In the meantime, virtually all patients can be diagnosed and treated on an ambulatory basis. The introduction of the monoclonal antibody rituximab (R) in combination with chemotherapeutic agents, has led to the development of highly potent forms of chemoimmunotherapy. In the case of aggressive lymphomas, R-CHOP has been shown to be significantly superior to CHOP alone, both in elderly and younger patients. In stage III and IV indolent (follicular) lymphomas, rituximab/chemotherapy combinations achieve response rates in excess of 90%, and prolonged progression-free survival rates which, for the first time hold out hope of a cure. Monoclonal antibodies that can be coupled to radioisotopes open up new possibilities for potent radioimmunotherapy which look promising for effecting a cure or long-lasting palliation in additional proportion of the patients.

Outpatient therapy in metastatic breast cancer. A retrospective study of 90 patients treated in an oncology group practice.

BACKGROUND: Whenever possible, treatment of breast cancer should be performed in an outpatient setting, but only few data about patients being treated exclusively on an outpatient basis are available. PATIENTS AND METHODS: A retrospective analysis was performed in 90 unselected patients who were treated consecutively in our oncology group practice between 6/95 and 8/99. RESULTS: Median age at detection of metastases was 55 years (30-90) and performance status ranged from 0 to 2. 83 patients (92.2%) received chemotherapy, 7 (7.8%) received endocrine therapy only. CMF was used in 27.7%, anthracyclines in 71.1% and taxanes in 43.3%. 855 chemotherapy cycles were performed and the observed toxicity was mild. Reversible grade 3 and 4 hematotoxicity was seen after 27 cycles (3.2%). Neurotoxicity or mucositis grade 3 and 4 were seen in 6 patients (6.6%). Therapy-associated hospitalization occurred in 1 patient thrice due to febrile neutropenia. Complete remissions were seen in 5 patients (5.6%) during first-line therapy. Median survival of the whole cohort until the end of the follow-up period (2/03) was 28 months (2-259). Overall survival after 1, 2, 3 and 5 years was 83, 56, 33 and 18% respectively. 50% could die at home. CONCLUSIONS: Treatment of metastatic breast cancer can be performed with minimal toxicity and a high patient acceptance in the outpatient setting. Overall survival and median survival are comparable to historical results achieved in specialized academic hospitals. Hospitalization could be avoided in the majority of patients and half of them could die at home.

Palliative treatment of advanced pancreatic carcinoma in community-based oncology group practices.

This study was aimed at evaluating the feasibility, effectiveness, and toxicity of palliative chemotherapy/supportive care in patients with advanced pancreatic cancer being treated on an outpatient basis. A retrospective analysis was performed on 127 consecutive, unselected patients with advanced pancreatic cancer in four community-based oncology group practices. Median age was 63 years and WHO performance status ranged from 0 to 3. Forty-three patients (34%) had locally advanced disease, and 84 patients (66%) had distant metastases; 94 patients (74%) received cytotoxic treatment during the course of their disease, and 33 (26%) received best supportive care only. First-line treatment consisted of gemcitabine (1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle) in 81 patients (86%), 5-fluorouracil (5-FU) in 8 patients (9%), radiochemotherapy in 4 patients (4%), and radiation therapy only in 1 patient (1%). A total of 1,501 gemcitabine treatments were given during the study period. Toxicity was moderate. Four patients (3%) required hospitalization for treatment-related side effects, and 111 patients (88%) died during the observation period. Symptom control, as measured by reduction of pain medication, was seen in 25% of patients receiving gemcitabine, whereas no reduction in pain medication was seen in the best supportive care group. The median survival of patients receiving cytotoxic treatment (mainly gemcitabine) was 42 weeks, and the median survival of patients receiving best supportive care was 21 weeks. The overall survival rate at 6, 12, 24, and 36 months was 65%, 32%, 14%, and 7%, respectively. Based on these outcomes, it appears that patients with locally advanced and metastatic pancreatic cancer benefit from adequate palliative treatment, including cytotoxic chemotherapy with gemcitabine, and this can be accomplished on an outpatient basis.

High affinity recognition of a Phytophthora protein by Arabidopsis via an RGD motif.

The RGD tripeptide sequence, a cell adhesion motif present in several extracellular matrix proteins of mammalians, is involved in numerous plant processes. In plant-pathogen interactions, the RGD motif is believed to reduce plant defence responses by disrupting adhesions between the cell wall and plasma membrane. Photoaffinity cross-linking of [125I]-azido-RGD heptapeptide in the presence of purified plasma membrane vesicles of Arabidopsis thaliana led to label incorporation into a single protein with an apparent molecular mass of 80 kDa. Incorporation could be prevented by excess RGD peptides, but also by the IPI-O protein, an RGD-containing protein secreted by the oomycete plant pathogen Phytophthora infestans. Hydrophobic cluster analysis revealed that the RGD motif of IPI-O (positions 53-56) is readily accessible for interactions. Single amino acid mutations in the RGD motif in IPI-O (of Asp56 into Glu or Ala) resulted in the loss of protection of the 80-kDa protein from labelling. Thus, the interaction between the two proteins is mediated through RGD recognition and the 80-kDa RGD-binding protein has the characteristics of a receptor for IPI-O. The IPI-O protein also disrupted cell wall-plasma membrane adhesions in plasmolysed A. thaliana cells, whereas IPI-O proteins mutated in the RGD motif (D56A and D56E) did not.

[Severe lead poisoning due to Ayurvedic indian plant medicine]. / Chronische Bleivergiftung durch ayurvedische Heilpillen.

HISTORY AND CLINICAL FINDINGS: A 39-year-old woman with a history of slowly progressive muscular dystrophia was transferred to us for further evaluations of a hypochromic, microcytic anaemia. The patient complained about progressive muscle weakness, loss of appetite and constipation, sleep disorders as well as muscle and back pain. Clinical examination revealed a tetraparesis without any detectable muscle reflexes and atrophic muscles of the extremities. A bilateral radial paresis was found with a loss of power. INVESTIGATIONS: She presented with a hypochromic, microcytic anaemia with a haemoglobin of 7.9 g/dl. Re-evaluation of her peripheral blood smear showed basophilic stippling of the erythrocytes. Bone marrow biopsy revealed a marked dyserythropoiesis with 50% ring sideroblasts. After the examination of the bone marrow, the blood lead level was found to be grossly elevated up to 880 microg/l. DIAGNOSIS: Re-evaluation of the patient's history revealed that she had been to India for an Ayurvedic treatment approach to improve her muscle dystrophia. She had taken regularly 4 different natural plant pills which she had bought in an Ayurvedic health centre. Toxicologic analysis of these pills revealed one to have a lead concentration of 50.4 mg/g. TREATMENT AND COURSE: The patient was treated with 16 infusions of sodium-EDTA followed by a 4-week treatment with dimercaptopropionic acid orally. Her neurological condition improved and the radial paresis resolved gradually so that she could return to work. Her haematological parameters normalized. CONCLUSION: This case report underscores the importance, while asking patients for their drug history, to ask additionally if natural plant medicine is taken or applied regularly. The report reveals that Ayurvedic pills from India may have a high concentration of lead and may cause severe poisoning.

Successful long-term treatment of systemic lupus erythematosus with rituximab maintenance therapy.

Systemic lupus erythematosus (SLE) is a chronic, inflammatory autoimmune disease that may involve multiple organ systems. Treatment consists of immunosuppression, cytotoxic treatment, plasmapheresis and immunoglobuline therapy. Treatment of patients refractory to standard treatment approaches is difficult and results are poor. We describe a 39-year old patient with SLE suffering from grand mal epilepsy due to cerebral vasculopathy with positive lupus anticoagulant, who was refractory to standard treatment modalities. The patient was treated with the anti-CD20 monoclonal antibody rituximab (375 mg/m2 x 4, repeated at weekly intervals). Rituximab applications were delivered in October 2000, March 2001 and October 2001. Since March 2002 she has received maintenance therapy with rituximab 375 mg/m2 every three months. A second female with refractory SLE was treated successfully in April 2002 and receives maintenance therapy every three months. Both patients responded well to rituximab therapy. The first patient showed a major improvement of her clinical condition, and 30 months after the beginning of the rituximab therapy she is free of any symptoms. Inflammation parameters, ANA and lupus anticoagulant declined significantly after the treatment. The clinical condition of the second patient improved dramatically, all inflammation parameters normalized and her circulating immunocomplexes disappeared. In conclusion, rituximab maintenance treatment may be a new effective therapy in SLE.

Localization of intravascular devices with paramagnetic markers in MR images.

Magnetic resonance imaging (MRI) offers potential advantages over conventional X-ray techniques for guiding and evaluating intravascular interventions. The development of methods to safely and robustly localize and track devices under MRI guidance is mandatory to enable automatic scan plane adaptation so as to exploit the three-dimensional imaging capabilities of the MRI scanner. With regard to the issue of radiofrequency-induced heating, passive approaches to catheter tracking are inherently safe. These techniques visualize intravascular devices by exploiting the susceptibility artifacts associated with the devices. To promote conspicuity, the devices are equipped with paramagnetic markers. This paper introduces a method to enable automatic localization of devices by its ability to recognize markers in two-dimensional MR images. The method requires a coarse segmentation of the vasculature of interest, and consists of two steps. First, it performs a series of postprocessing operations including calculation of the winding number image and of the Laplacian image to detect marker candidates in the image. Second, the device is localized by matching the detected pattern of candidates to the known distance template of the device markers. Results of an animal experiment and of a clinical application are demonstrated. Validation in phantom experiments shows that the method is able to localize the device in 95% of the cases.

Dose reduction of steroid premedication for paclitaxel: no increase of hypersensitivity reactions.

BACKGROUND: Premedication with dexamethasone, ranitidine and clemastine is mandatory for patients receiving paclitaxel to avoid hypersensitivity reactions. The proposed dexamethasone dose is 20 mg orally 12 and 6 h prior to paclitaxel infusion. With this premedication severe hypersensitivity reactions are reduced to 1-2% of the treated patients. Besides this oral schedule a single dose of dexamethasone, 40 mg given i.v., just prior to paclitaxel has been shown to be equally effective. In an attempt to reduce steroid-induced side effects, especially for patients receiving weekly paclitaxel protocols, we reduced the dexamethasone dose. PATIENTS AND METHODS: A total of 132 patients were treated on an outpatient basis with paclitaxel-containing protocols. Paclitaxel was given in doses of 135-175 mg/m(2) once every 3 weeks in 76 patients and/or with 100 mg/m(2) weekly in 70 patients. Dexamethasone premedication was given in a single dose (40, 20, 10 mg) as an infusion directly before paclitaxel. RESULTS: 0/46 patients receiving 40 mg dexamethasone premedication in 235 cycles and 0/48 patients receiving 20 mg dexamethasone premedication in 186 cycles experienced a severe hypersensitivity reaction. 1/52 patients receiving 10 mg dexamethasone in 480 applications developed a severe hypersensitivity reaction with bronchospasm, hypotension and supraventricular tachycardia shortly after her first paclitaxel infusion started. CONCLUSION: No increase of severe hypersensitivity reactions is seen when dexamethasone premedication is reduced to doses of 20 or even 10 mg prior to paclitaxel infusion.

Placement of an inferior vena cava filter in a pig guided by high-resolution MR fluoroscopy at 1.5 T.

Percutaneous placement of an inferior vena cava filter is a means for long-term prevention of pulmonary thromboembolism. In this study we investigated the magnetic resonance (MR) imaging properties of a Nitinol vena cava filter, in various anatomic and angiographic scans, as well as the feasibility of placing this filter under near real-time, high-resolution MR fluoroscopy. We made use of the passive tracking strategy, with on-line image processing and visualization, both in vitro and in a pig. The artifacts provoked by the metallic filter were such that the position and orientation of the filter were well depicted in all scans. Considerable radiofrequency caging obscured the interior of the filter. Our experiments showed that an MR-guided vena cava filter placement, with sufficient temporal and spatial resolution, is possible. Three-dimensional phase contrast MRA allowed direct evaluation of the filter placement procedure, without the use of contrast agent.