Christel Fontaine

Catheter tip position as a risk factor for thrombosis associated with the use of subcutaneous infusion ports

AimsThe use of subcutaneous infusion ports has become standard practice to provide a long-term venous access in oncological patients. The aim of this retrospective study was to assess the different complications of infusion ports in our population and to identify predisposing factors.Patients and methodsWe reviewed the medical records of 437 patients who were followed at the Oncology/Haematology Department of our hospital. Of these patients, there were 370 (84.4%) with solid tumours and 58 (13.2%) with haematological disease. The position of the catheter tip was evaluated by reviewing the available chest radiographs or phlebographies.Main resultsAnalysis of the records showed that 346 patients (79.17%) had no complications. The most common complications after implantation were thrombosis (8.46%), catheter dysfunction (4.8%) and infections (4.4%). Univariate and multivariate analysis showed that catheter tip positioning was the most important predisposing risk factor for thrombosis. Catheter tips positioned in the brachiocephalic vein or in the cranial part of the superior vena cava were associated with a high risk of thrombosis. Other significant risk factors were gender and initial diagnosis. Female patients and patients with lung cancer also had an elevated risk of developing a thrombosis.ConclusionsCompared to other reports, we noted a higher rate of thrombosis and port dysfunction. Since catheter tip position was a predisposing factor for developing a thrombosis, correct catheter position has to be ensured during placement. Prophylactic antithrombotic treatment might be beneficial in the event of failure to position the catheter correctly.

Phase I Study of 68Ga-HER2-Nanobody for PET/CT Assessment of HER2 Expression in Breast Carcinoma

Human epidermal growth factor receptor 2 (HER2) status is one of the major tumor characteristics in breast cancer to guide therapy. Anti-HER2 treatment has clear survival advantages in HER2-positive breast carcinoma patients. Heterogeneity in HER2 expression between primary tumor and metastasis has repeatedly been described, resulting in the need to reassess HER2 status during the disease course. To avoid repeated biopsy with potential bias due to tumor heterogeneity, Nanobodies directed against HER2 have been developed as probes for molecular imaging. Nanobodies, which are derived from unique heavy-chain-only antibodies, are the smallest antigen-binding antibody fragments and have ideal characteristics for PET imaging. The primary aims were assessment of safety, biodistribution, and dosimetry. The secondary aim was to investigate tumor-targeting potential. Methods: In total, 20 women with primary or metastatic breast carcinoma (score of 2+ or 3+ on HER2 immunohistochemical assessment) were included. Anti-HER2-Nanobody was labeled with 68Ga via a NOTA derivative. Administered activities were 53–174 MBq (average, 107 MBq). PET/CT scans for dosimetry assessment were obtained at 10, 60, and 90 min after administration. Physical evaluation and blood analysis were performed for safety evaluation. Biodistribution was analyzed for 11 organs using MIM software; dosimetry was assessed using OLINDA/EXM. Tumor-targeting potential was assessed in primary and metastatic lesions. Results: No adverse reactions occurred. A fast blood clearance was observed, with only 10% of injected activity remaining in the blood at 1 h after injection. Uptake was seen mainly in the kidneys, liver, and intestines. The effective dose was 0.043 mSv/MBq, resulting in an average of 4.6 mSv per patient. The critical organ was the urinary bladder wall, with a dose of 0.406 mGy/MBq. In patients with metastatic disease, tracer accumulation well above the background level was demonstrated in most identified sites of disease. Primary lesions were more variable in tracer accumulation. Conclusion: 68Ga-HER2-Nanobody PET/CT is a safe procedure with a radiation dose comparable to other routinely used PET tracers. Its biodistribution is favorable, with the highest uptake in the kidneys, liver, and intestines but very low background levels in all other organs that typically house primary breast carcinoma or tumor metastasis. Tracer accumulation in HER2-positive metastases is high, compared with normal surrounding tissues, and warrants further assessment in a phase II trial.

Fulvestrant (Faslodex) in advanced breast cancer: clinical experience from a Belgian cooperative study.

Fulvestrant (Faslodex™) is a new estrogen receptor (ER) antagonist with no agonist effects that is licensed for the treatment of postmenopausal women with hormone-sensitive advanced breast cancer (ABC) who have progressed/recurred on prior antiestrogen therapy. The Faslodex™ Compassionate Use Program (CUP) provides expanded access to fulvestrant in countries where it is not yet available for patients who are not eligible to enter clinical trials. This analysis pools data from 402 patients who received fulvestrant as part of the CUP in Belgium, predominantly as 3rd- to 5th-line endocrine therapy for ABC. Two patients experienced partial responses and 118 experienced stable disease lasting ≥6 months, resulting in an overall clinical benefit rate of 29.9%. Fulvestrant was active in patients with multiple sites of metastases, visceral metastases, human epidermal growth factor receptor 2-positive disease and after heavy endocrine pre-treatment. Fulvestrant was well tolerated, with only six patients (1.5%) discontinuing treatment following adverse events. These data support the findings of previous CUP analyses and Phase II and III trials, suggesting that fulvestrant is a valuable addition to the treatment sequence for postmenopausal women with ABC who have progressed/recurred on prior endocrine therapy.

Savene® (dexrazoxane) use in clinical practice

IntroductionAnthracycline extravasation (ACEV) is a rare but potentially devastating event which can result in severe injuries including ulceration and necrosis, slow-healing lesions, serious joint damage and permanent disfigurement. It can delay further scheduled chemotherapy and affect cancer treatment outcome. Savene® (dexrazoxane) is the only approved antidote for ACEV in Europe (Totect® in the USA) and is administered by intravenous infusion. Its efficacy has been demonstrated in clinical trials with biopsy-verified ACEV with a 98% success rate (no need for surgical debridement) allowing for immediate continuation of chemotherapy in 71% of patients. Adverse events, mainly haematological toxicity, were rapidly reversible. The objective of the study was to assess, in clinical practice, the efficacy and safety profile of Savene® for ACEV in different Belgian hospitals.Patients and methodsA survey of Savene® use was conducted in Belgium from 2007 to 2010 by using a questionnaire sent to 44 hospitals.Main resultsData were obtained for 41 cancer patients, 68% (28/41) had ACEV from central venous catheters. Surgical debridement due to ACEV could be avoided in 26 out of 28 extravasations from a central venous access and in 95% (39/41) of the total population treated with Savene®. Planned chemotherapy was maintained in 73% (30/41) of patients. Eight adverse events were reported in four patients treated with Savene®, six events were assessed to be of common toxicity criteria grades 1–2 (nausea, leucopenia and arm pain) and two events (neutropenia and pancytopenia) were assessed to be grade 3.ConclusionThese data are comparable with the data from previous clinical trials and confirm the efficacy and safety profile of Savene® in clinical practice for the treatment of anthracycline extravasation, including extravasations from central venous catheters.

Evaluation of a Comprehensive Rehabilitation Program for Post-Treatment Patients With Cancer

PURPOSE/OBJECTIVES To evaluate the effects of a rehabilitation program on quality of life, fatigue, fear of movement (kinesiophobia), distress, anxiety, depression, and physical condition. DESIGN Pretest/post-test. SETTING An outpatient rehabilitation setting in the Oncology Centre at the University Hospital Brussels in Belgium. SAMPLE 36 patients who had completed cancer treatment with a curative potential. METHODS Participants completed a questionnaire and underwent a physical test at baseline and at the end of the program. The measurement instruments used included the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30, Functional Assessment of Cancer Therapy-Fatigue, Hospital Anxiety and Depression Scale, RAND-36, Tampa Scale for Kinesiophobia, Distress Barometer, and Tecumseh Step Test. MAIN RESEARCH VARIABLES Quality of life, fatigue, kinesiophobia, distress, anxiety, depression, and physical condition. FINDINGS Significant improvement was observed in quality of life (p < 0.001), physical condition (p = 0.007), fatigue (p = 0.01), and depression (p = 0.012). In contrast, kinesiophobia (p = 0.229), distress (p = 0.344), and anxiety (p = 0.101) did not change significantly. CONCLUSIONS A general and significant improvement in all aspects affecting quality of life and rehabilitation was observed, but less so for aspects that might be influenced by prognostic concerns. The relative contribution of the program versus spontaneous recovery and long-term impact need to be determined further in a prospective randomized study. IMPLICATIONS FOR NURSING Multidisciplinary rehabilitation should become part of the total care plan for patients with cancer.

Severe thrombocytopenia secondary to cytomegalovirus infection in an immunocompetent adult.

A healthy 38-year-old man presented with a short history of a viral syndrome, accompanied by purpura and gingival bleeding. Examination of the blood showed a profound thrombocytopenia. Cytomegalovirus infection was diagnosed and a causal relationship between CMV infection and thrombocytopenia was assumed on clinical grounds. We successfully treated the patient with oral prednisone. In the discussion, we briefly mention the different hypothetical mechanisms leading to autoimmune thrombocytopenia.

Final Overall Results of a Study with a Novel Triplet Induction Chemotherapy Regimen (PACCAGE) Followed by Consolidation Radiotherapy in Locally Advanced Inoperable Non-small Cell Lung Cancer (NSCLC)

Introduction: We report the long term and overall results of a triplet induction chemotherapy regimen followed by standard radiotherapy in patients with locally advanced inoperable stage III non-small cell lung cancer. Methods: Three cycles of paclitaxel, carboplatin, and gemcitabine were administered every 3 weeks before standard fractionated consolidation radiotherapy starting at least 4 weeks after the last chemotherapy administration. Toxicity and antitumor response was assessed in detail as well as the progression free and overall survival. Results: Sixty-four patients (25 stage IIIA and 39 stage IIIB) received a total of 179 cycles of chemotherapy. Fifty-six received the planned three cycles. Full-dose radiotherapy was administered in 47 patients (73%), a reduced dose in 11 (17%) and none in six (10%). A 55% objective response rate (OR) (one complete and 34 partial responses) was observed after induction chemotherapy. After completing the whole treatment including radiotherapy, the OR was 40 of 47 evaluable patients (85%). Median time to progression was 10.9 month and median overall survival was 17.2 month, with a significant difference between stage IIIA and stage IIIB patients (23.4 versus 10.5 month; p = 0.011). The strongest predictor for a favorable long-term outcome was a metabolic complete response after chemotherapy. Conclusion: Induction chemotherapy with the paclitaxel, carboplatin, and gemcitabine regimen preceding radiotherapy in patients with locally advanced inoperable stage III non-small cell lung cancer was feasible and active. Radiotherapy could be administered at a full dose in the majority of patients with acceptable toxicity. Long-term survival results of this sequential chemoradiotherapy regimen appear similar to those of concurrent treatment. Patients not achieving a metabolic complete response after induction chemotherapy should be the focus of studies aiming at improved local control.

Randomized Phase II Study of Cabazitaxel Versus Methotrexate in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With Platinum-Based Therapy

Lessons Learned Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. For the first time, cabazitaxel was investigated in incurable patients with recurrent SCCHN. Patients were randomly assigned to cabazitaxel every 3 weeks or weekly methotrexate. This phase II study did not meet its primary endpoint. Cabazitaxel has low activity in SCCHN. The toxicity profile in this population also was not favorable owing to the high rate of febrile neutropenia observed (17%). Background. Cabazitaxel is a second-generation taxane that improves the survival of patients with metastatic castrate-resistant prostate cancer following docetaxel therapy. Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. In this randomized phase II trial, we investigated cabazitaxel in patients with recurrent SCCHN. Methods. Patients with incurable SCCHN with progression after platinum-based therapy were randomly assigned to cabazitaxel every 3 weeks (cycle 1, 20 mg/m2, increased to 25 mg/m2 for subsequent cycles in the absence of nonhematological adverse events [AEs] greater than grade 2 and hematological AEs greater than grade 3) or methotrexate (40 mg/m2/week). The patients were stratified according to their performance status and previous platinum-based chemotherapy for palliation versus curative intent. The primary endpoint was the progression-free survival rate (PFSR) at 18 weeks. Results. Of the 101 patients, 53 and 48, with a median age of 58.0 years (range, 41–80), were randomly assigned to cabazitaxel or methotrexate, respectively. The PFSR at 18 weeks was 13.2% (95% confidence interval [CI], 5%–25%) for cabazitaxel and 8.3% (95% CI, 2%–20%) for methotrexate. The median progression-free survival was 1.9 months in both arms. The median overall survival was 5.0 and 3.6 months for cabazitaxel and methotrexate, respectively. More patients experienced serious adverse events with cabazitaxel than with methotrexate (54% vs. 36%). The most common drug-related grade 3–4 AE in the cabazitaxel arm was febrile neutropenia (17.3%). Conclusion. This study did not meet its primary endpoint. Cabazitaxel has low activity in recurrent SCCHN.

The influence of multidisciplinary rehabilitation on physical well-being and quality of life of breast cancer survivors.

143 Background: Breast cancer treatment has adverse effects. The aim of this study was to examine the effects of a multidisciplinary oncologic rehabilitation program on health related quality of life (HRQoL), cancer related fatigue (CRF), muscle strength, physical fitness and anthropometrics in breast cancer survivors. METHODS This quasi-experimental study included 30 early breast cancer patients in the first year following treatment. Patients completed a 12-week exercise program for 4 hours a week combined with lifestyle guidance for 2 hours a week. The supervised training sessions consisted of aerobic exercises combined with muscular strengthening exercises. Measurements were carried out at baseline (T0), at the end of the intervention (T1) and at 12-weeks follow-up (T2). HRQoL (EORTC QLQ-C30 questionnaire) and CRF (FACIT-Fatigue questionnaire), were measured at T0, T1 and T2. Muscle strength (handgrip dynamometer) was measured at T0 and T1. Physical fitness and anthropometrics were assessed at T0 and T1 using spiro ergometrics, bioimpedance and waist- and hip circumference. RESULTS Significant positive changes in HRQoL were found, especially for physical functioning (p = 0.004) and dyspnea (p = 0,003) at T1, but HRQoL decreased at T2. Weight, BMI, waist - and hip circumference and fat free mass decreased significantly (respectively p = 0,030; p = 0,047; p = 0,020; p = 0,041 and p = 0,003). Body impedance increased significantly over time (p = 0,034). There was a significant improvement in CRF at T1 (p = 0.03), that was no longer significant at T2. No significant improvements were found in muscle strength at the affected side (p = 0.16) and the non-affected side (p = 0.95). Physical fitness increased significantly for VO2max at the maximal progressive cycle test (p = 0.005). CONCLUSIONS This study reports significant improvements in HRQoL, anthropometric characteristics, CRF and physical fitness after a 12-week rehabilitation program. The declines between T1 and T2 may be explained by discontinuation of physical activity. Further research should use randomized clinical trials to examine the effectiveness of rehabilitation programs with different contents, duration and initiation.

The effect of a varied exercise program (VEP) on shoulder function and lymphedema (LE) in breast cancer survivors (BCs): A pilot study.

82 Background: A common physical sequel after adjuvant therapy is a decrease in shoulder movement of the upper-limb of the affected side and the development of LE. Resistance exercise is known to be safe and does not increase the risk of LE. The objective of this study is to evaluate the effect of a VEP on shoulder range of motion and upper-limb LE after adjuvant therapy in BCs. METHODS 22 BCs treated with surgery and adjuvant therapy were randomly assigned to the VEP (n=12) or the control (n=10). The VEP aimed at improving aerobic endurance, joint mobility and muscle strength. The frequency of the VEP was 2 times a week, during 3 months, with a total of 30 sessions. Primary endpoints included the range shoulder motion and arm volumes of both arms. The secondary outcome was quality of life (QoL) as measured by the EORTC QLQ-C30. All outcome measures were assessed at baseline and after 3 months. RESULTS After ending the VEP, in the exercise group, the movements such as abduction (p=0.04), external rotation (p=0.02), extension (p=0.03) and flexion (p=0.01) of the affected arm increased significantly but there was no change for internal rotation (0.27). No significant changes in arm volume (p=0.06) were found after 3 months compared to baseline, whereas the quality of life did improve significantly (p=0.01). After 3 months the range of motion of the shoulder of the affected arm (sum of abduction, external rotation, extension and flexion) in the exercise group tended to be better although this was not significant (p=0.50). The arm volume difference between the two groups was not significant (p=0.10) but it was for the QoL (p=0.02). CONCLUSIONS A VEP lead to significant specific improvements in arm mobility compared to baseline. These BCs also compared favourably to the control cohort, but this was not significant. The study confirms that exercising the ipsilateral arm and shoulder has no detrimental effect on LE and has a positive impact on the QoL. Standard guidelines concerning physical therapy to ameliorate shoulder function and LE are not available. Additional patients will be enrolled to develop standard recommendations for physical therapy to improve shoulder and limb function in BCs.