Circulating tumor cell count and thrombosis in metastatic breast cancer.

Essentials Tumor cells circulating in blood (CTC) may favor thrombotic events in cancer patients. We assessed the impact of CTC on the risk of thrombosis in metastatic breast cancer. Baseline CTC detection was the only independent factor associated with the risk of thrombosis. CTC detection under therapy may be the hidden link between tumor progression & thrombosis. SUMMARY: Background Circulating tumor cell (CTC) count is a major prognostic factor in metastatic breast cancer (MBC) and has been reported to be associated with thrombosis in short-term studies on MBC patients. Objective To assess whether CTC detection (CellSearch® ) before first-line chemotherapy impacts the risk of thrombosis throughout the course of MBC. Patients/Methods Among patients included before first-line chemotherapy for MBC in the prospective IC2006-04 CTC detection study (NCT00898014), the electronic medical files of those patients treated at Institut Curie (Paris, France) were searched in silico and manually checked for incident venous or arterial thrombotic events (TE) in the course of MBC. Univariate and multivariate analyses were performed using Cox and Fine-Gray models, adjusted for age and Khorana score. Results/Conclusions With a median follow-up of 64 months (25-81 months), among the 142 patients included, 34 (24%) experienced a TE (incidence rate, 8 TE/100 patient-years). The TE incidence rate was 13 TE/100 patient-years for the 80 patients with ≥ 1 CTC/7.5 mL of blood before initiating first-line chemotherapy, vs. only 4 TE/100 patient-years for the 62 CTC-negative patients. Fine-Gray multivariate analysis (with death as competing event) included age, Khorana score and baseline lactate dehydrogenase and CTC levels: detectable CTC was the only factor significantly associated with an increased risk of TE (sub-distribution hazard ratio [SHR] for patients with [1-4] CTC = 3.1, 95% CI [1.1; 8.6], SHR for patients with ≥ 5 CTC = 1.4, 95% CI [0.5; 4.6]). This study shows that CTC detection before starting first-line chemotherapy is an independent risk factor for TE in MBC patients.

Survival of breast cancer patients with meningeal carcinomatosis treated by intrathecal thiotepa.

Treatment of breast cancer meningeal carcinomatosis (MC) relies on intrathecal chemotherapy. Thiotepa is one of the few drugs approved in this setting, although no large cohort has been reported. The aim of our retrospective study is to describe survival and prognostic factors of breast cancer patients treated by intrathecal thiotepa. A search in the electronic database of the Institut Curie was performed and retrieved the patients diagnosed with breast cancer MC from 2000 to 2012 and who received at least one intrathecal injection of thiotepa. The standard regimen was intrathecal thiotepa (10 mg) and methylprednisolone (40 mg), repeated every other week. Clinical data were retrieved from the computerized medical file of each patient. Sixty-six patients have been treated with intrathecal thiotepa either as first line or second line of treatment for breast cancer MC. The median overall survival was 4.5 months (range 0.1-50). There was no significant survival difference between patients treated as first or second line. In multivariate analysis, main adverse prognostic factors at diagnosis were performance status >2 (p = 0.001, RR = 3.4, 95 % CI 1.6-7.2) and history of more than 3 previous systemic chemotherapy lines (p = 0.002, RR = 2.90, 95 % CI 1.50-5.65). After start of the treatment, high primary tumor grade, elevated Cyfra 21-1 levels in the cerebrospinal fluid, and lack of clinical improvement were also independent adverse prognostic factors in multivariate analysis. This is the largest retrospective cohort of breast cancer MC treated by intrathecal thiotepa ever reported. The median overall survival was short but some patients clearly benefited from this treatment, even used as second line.

Necrosis in breast cancer patients with skin metastases receiving bevacizumab-based therapy.

OBJECTIVE: Bevacizumab has entered daily practice in advanced breast cancer patients, in whom skin metastases occurrence is a common event. Wound healing impairment has been described with bevacizumab, and this study looks at possible deleterious side effects of bevacizumab in patients with skin metastases. METHOD: We retrospectively reviewed a series of 12 patients with advanced breast cancer presenting extensive skin metastases, and who received bevacizumab based therapy. RESULTS: Nine patients who initially presented with erosive skin lesions developed extensive and durable skin necrosis, as well as delayed healing of surgical flaps, despite early discontinuation of bevacizumab therapy and intensive skin care in a specialised unit. Skin necrosis was usually associated with extensive tumoural involvement of the skin. CONCLUSION: Bevacizumab may be harmful in selected breast cancer patients with metastatic cutaneous involvement.

Acceptance of the 2009 A(H1N1) influenza vaccine among hospital workers in two French cancer centers.

The aim of the study was to determine predictive factors influencing the acceptance of the 2009 A(H1N1) influenza vaccination among hospital workers (HW) in two French cancer centers. A standardized, anonymous, self-administered questionnaire was sent to HW of two cancer centers. The survey response rate was 26.2% (n=506). Main reasons for A(H1N1) vaccination acceptance were "to protect my relatives" (30.3%), "to protect myself" (30.3%). Main reasons for A(H1N1) vaccination refusal were the fear of side effects (43.1%), doubt about the vaccine's efficacy (25.8%). Vaccinated HW were more influenced by the institutional campaign (p<0.001) or colleagues' advice (p<0.001) whereas non-vaccinated HW were influenced by their family physician's advice (p=0.03), personal conviction (p<0.001) or the media (p<0.001). A multivariate analysis revealed age (>35 vs ≤ 35), prior seasonal influenza vaccination, professional category and source of information to be predictive factors of vaccination. Future vaccination campaigns will need to focus on young HW (≤ 35-year old), with no prior influenza vaccination and HW who are in contact with patients and who reported low seasonal influenza vaccination rates.

2008 SOR guidelines for the prevention and treatment of thrombosis associated with central venous catheters in patients with cancer: report from the working group.

BACKGROUND: In view of the lack of recommendations on central venous catheter (CVC)-associated thrombosis in cancer patients, we established guidelines according to the well-standardized Standards, Options and Recommendations methodology. MATERIAL AND METHODS: A literature review (1990-2007) on CVC-associated thrombosis was carried out. The guidelines were developed on the basis of the corresponding levels of evidence derived from analysis of the 36 of 175 publications selected. They were then peer reviewed by 65 independent experts. RESULTS: For the prevention of CVC-associated thrombosis, the distal tip of the CVC should be placed at the junction between the superior cava vein and right atrium; anticoagulants are not recommended. Treatment of CVC-associated thrombosis should be based on the prolonged use of low-molecular weight heparins. Maintenance of the catheter is justified if it is mandatory, functional, in the right position, and not infected, with a favorable clinical evolution under close monitoring; anticoagulant treatment should then be continued as long as the catheter is present. CONCLUSIONS: Several rigorous studies do not support the use of anticoagulants for the prevention of CVC-associated thrombosis. Treatment of CVC-associated thrombosis relies on the same principles as those applied in the treatment of established thrombosis in cancer patients.

[Encapsulated implantable venous access device: two clinical cases]. / Cathéter à chambre implantable inextirpable: à propos de deux cas cliniques.

We report two cases of encapsulated indwelling central venous catheter in adults. The patients involved were treated by chemotherapy and their catheter had been implanted for 15 and 6 years. However, this complication is well-known in children and a similar problem is frequently observed with pacemaker leads removal. The difficulty to remove the device is due to fibrous encapsulation of indwelling catheters in the vein wall. In all cases reported, the catheter was left in place. The potential main complications not yet observed are infection of the catheter and venous thrombosis.

[Using a pleural implantable access system for the management of malignant pleural effusions. Experience of Institut Curie]. / Utilisation du cathéter à chambre implantable pleural dans la gestion des pleurésies malignes. Expérience de l'Institut Curie.

PURPOSE: Malignant pleural effusion has a very poor prognosis, raises problems of medical management and impairs quality of life. The authors report the first experience of a pleural implantable access system for the treatment of recurrent symptomatic malignant pleural effusion. DESCRIPTION: Prospective follow-up of 26 patients between 20/8/2005 and 2/11/2006 in a single center. Thirty pleural implantable access systems were placed in 26 patients (22 patients with breast cancers, 3 bilateral placements and one case of replacement) under sedation following the decision of a multidisciplinary meeting. EVALUATION: Twenty-five patients obtained partial or complete relief of their dyspnea. Four patients underwent spontaneous pleurodesis after a maximum of 2 months. Twelve patients were receiving chemotherapy at the time of placement. The number of aspirations performed varied between 1 and 28 over a period of 11 to 330 days. Eight patients died within 1 month after placement of the system and 6 survived more than 6 months. Seven patients died at Institut Curie or in a palliative care unit without returning home. The other 16 patients presented a total of 198 days of hospitalization for 2,305 days of catheter implantation. No placement failures were observed in this series. Two infectious complications (infectious pleuro-pneumonia and skin infection over the puncture site) and two mechanical complications (expulsion of the port and disconnection between the port and the catheter) were observed and easily treated. One patient developed loculation of the pleural cavity after 16 thoracenteses making further thoracentesis ineffective. CONCLUSIONS: The pleural implantable access system is an interesting alternative in terms of efficacy and safety for the outpatient management of malignant pleural effusion. It shows a number of advantages in terms of comfort and infectious risk compared to tunneled pleural catheters.

[Symptomatic thrombosis in central venous catheter in oncology: a predictive score?]. / Thrombose symptomatique sur cathéter veineux central de longue durée en oncologie: un score de risque prédictif?

BACKGROUND: Central venous catheters are essential to management of cancer patients. Thrombotic complications are potentially severe, but it is difficult to prescribe systematically a prophylactic treatment. So it is necessary to identify the higher risk patients who need a prophylaxis. AIM: To identify factors associated with the development of clinically significant venous thrombosis in cancer patients with long-term catheters. METHODS: Monocentric prospective study about 5447 long-term central venous catheters inserted into patients receiving treatment for solid tumours (50% of breast cancers). Clinically significant catheter-related thromboses are confirmed by ultrasonography, phlebography or scanner. RESULTS: The median duration of catheter use is 147 days. There are 135 clinically significant catheter-related thromboses. The risk for thrombosis is 0.1149 events per 1000 device days. The incidence of symptomatic thrombosis is 0.9% at 30 days, 1.36% at 60 days, 1.83% at 90 days and 2.25% at 120 days. The multivariate analysis shows that female sex, duration of insertion procedure (more than 25 minutes) and place of insertion (femoral place) are factors associated with clinically significant venous thrombosis. The right subclavian insertion causes less risk. The catheters with their tip too "high" in the superior vena cava are systematically changed, so that the position of the catheter tip does not appear as a risk factor in our study. The disease stage and the type of treatments are not well examined. CONCLUSIONS: A predictive score can be made with the three risk factors that have been identified. Thanks to this score it is possible to determine the patients with higher risk for clinically significant catheter-related venous thrombosis. These patients must be more frequently watched over and must receive a prophylactic treatment. The best prophylaxis has to be determined.

[Infectious sequellae of 913 central catheters in oncology]. / Suivi infectieux de 913 cathéters centraux en cancérologie.

Infections associated with central catheters are a significant source of morbidity in cancer patients. The first evaluation done as part of a continuous catheter surveillance program included the 913 central catheters inserted in 1995. Three of these catheters are still in place. All were tunneled subcutaneously, and most were inserted via the subclavian route. There were 839 simple silicone catheters and 74 catheters with a cuff. Two groups were defined based on whether the central catheter was inserted for administering inpatient or outpatient chemotherapy (n = 704) or for another reason (perioperative care, symptomatic or palliative therapy; n = 209). Catheter-related infection was defined as an infection at the catheter site or as septicemia retrospectively shown to be related to the catheter. The risk of catheter-related infection was expressed as the number of cases per 1000 days of catheterization. Reasons for catheter removal were distributed in table I.

[Treatment of acute postoperative pain]. / Traitement des douleurs aiguës post-opératoires.

Postoperative pain is a subjective experience involving sensations and perceptions, which may be the result of tissue damage after surgery. Various analgesic drugs and techniques can be used to relief postoperative pain. They must be adapted to the surgery and to the patient. Moreover, adequate management of postoperative pain need to be organized. This include medical attitudes, clinical orientations, disciplinary involvements, consultative protocols and program education.