Abscopal effect in metastatic renal cell carcinoma.

We report a case about a possible abscopal effect in a patient with metastatic renal cell carcinoma. Palliative conventional radiation of a metastatic lesion in the neck was performed and in the months after this treatment had been applied, clearance of the non-irradiated lung metastases and a subcutaneous nodule was observed. The abscopal effect is a phenomenon in which local radiotherapy is associated with regression of metastatic cancer at a distance from the irradiated site. It's a rare phenomenon; until now, only case reports and small series demonstrate the abscopal effect. This case supports the fact that further studying of this rare event must be encouraged.

Virtual anatomical reconstruction of large acetabular bone defects using a statistical shape model.

Custom implants are used to treat patients with large acetabular bone defects. To quantify the bone defect and to initialize the implant design, a virtual anatomical reconstruction of the bone needs to be performed. Our SSM-based reconstruction approach was used to overcome the limitations of the mirrored contralateral method and improves upon other SSM reconstruction techniques. The reconstruction errors for the acetabular direction, the hip joint center and the acetabular radius were, respectively: [Formula: see text], 2.6 mm and 0.7 mm. We believe that our method can be an essential tool in the planning and the design of custom implants.

Computed tomography-based joint locations affect calculation of joint moments during gait when compared to scaling approaches.

Hip joint moments are an important parameter in the biomechanical evaluation of orthopaedic surgery. Joint moments are generally calculated using scaled generic musculoskeletal models. However, due to anatomical variability or pathology, such models may differ from the patient's anatomy, calling into question the accuracy of the resulting joint moments. This study aimed to quantify the potential joint moment errors caused by geometrical inaccuracies in scaled models, during gait, for eight test subjects. For comparison, a semi-automatic computed tomography (CT)-based workflow was introduced to create models with subject-specific joint locations and inertial parameters. 3D surface models of the femora and hemipelves were created by segmentation and the hip joint centres and knee axes were located in these models. The scaled models systematically located the hip joint centre (HJC) up to 33.6 mm too inferiorly. As a consequence, significant and substantial peak hip extension and abduction moment differences were recorded, with, respectively, up to 23.1% and 15.8% higher values in the image-based models. These findings reaffirm the importance of accurate HJC estimation, which may be achieved using CT- or radiography-based subject-specific modelling. However, obesity-related gait analysis marker placement errors may have influenced these results and more research is needed to overcome these artefacts.

Modelling the effect of repositioning on the evolution of skeletal muscle damage in deep tissue injury.

Deep tissue injury (DTI) is a localized area of tissue necrosis that originates in the subcutaneous layers under an intact skin and tends to develop when soft tissue is compressed for a prolonged period of time. In clinical practice, DTI is particularly common in bedridden patients and remains a serious issue in todays health care. Repositioning is generally considered to be an effective preventive measure of pressure ulcers. However, limited experimental research and no computational studies have been undertaken on this method. In this study, a methodology was developed to evaluate the influence of different repositioning intervals on the location, size and severity of DTI in bedridden patients. The spatiotemporal evolution of compressive stresses and skeletal muscle viability during the first 48 h of DTI onset was simulated for repositioning schemes in which a patient is turned every 2, 3, 4 or 6 h. The model was able to reproduce important experimental findings, including the morphology and location of DTI in human patients as well as the discrepancy between the internal tissue loads and the contact pressure at the interface with the environment. In addition, the model indicated that the severity and size of DTI were reduced by shortening the repositioning intervals. In conclusion, the computational framework presented in this study provides a promising modelling approach that can help to objectively select the appropriate repositioning scheme that is effective and efficient in the prevention of DTI.

Towards a quantitative understanding of oxygen tension and cell density evolution in fibrin hydrogels.

The in vitro culture of hydrogel-based constructs above a critical size is accompanied by problems of unequal cell distribution when diffusion is the primary mode of oxygen transfer. In this study, an experimentally-informed mathematical model was developed to relate cell proliferation and death inside fibrin hydrogels to the local oxygen tension in a quantitative manner. The predictive capacity of the resulting model was tested by comparing its outcomes to the density, distribution and viability of human periosteum derived cells (hPDCs) that were cultured inside fibrin hydrogels in vitro. The model was able to reproduce important experimental findings, such as the formation of a multilayered cell sheet at the hydrogel periphery and the occurrence of a cell density gradient throughout the hydrogel. In addition, the model demonstrated that cell culture in fibrin hydrogels can lead to complete anoxia in the centre of the hydrogel for realistic values of oxygen diffusion and consumption. A sensitivity analysis also identified these two parameters, together with the proliferation parameters of the encapsulated cells, as the governing parameters for the occurrence of anoxia. In conclusion, this study indicates that mathematical models can help to better understand oxygen transport limitations and its influence on cell behaviour during the in vitro culture of cell-seeded hydrogels.

The effect of body mass index on overall and disease-free survival in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: the experience of the BIG 02-98 trial.

BACKGROUND: Obesity has been shown to be an indicator of poor prognosis for patients with primary breast cancer (BC) regardless of the use of adjuvant systemic therapy. PATIENTS AND METHODS: This is a retrospective analysis of 2,887 node-positive BC patients enrolled in the BIG 02-98 adjuvant study, a randomised phase III trial whose primary objective was to evaluate disease-free survival (DFS) by adding docetaxel to doxorubicin-based chemotherapy. In the current analysis, the effect of body mass index (BMI) on DFS and overall survival (OS) was assessed. BMI was obtained before the first cycle of chemotherapy. Obesity was defined as a BMI >or= 30 kg/m2. RESULTS: In total, 547 (19%) patients were obese at baseline, while 2,340 (81%) patients were non-obese. Estimated 5-year OS was 87.5% for non-obese and 82.9% for obese patients (HR 1.34; P = 0.013). Estimated 5-years DFS was 75.9% for nonobese and 70.0% for obese patients (HR 1.20; P = 0.041). Ina multivariate model, obesity remained an independent prognostic factor for OS and DFS. CONCLUSIONS: In this study,obesity was associated with poorer outcome in node-positive BC patients. Given the increasing prevalence of obesity worldwide, more research on improving the treatment of obese BC patients is needed.

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>or=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.

Phosphorylated HER-2 tyrosine kinase and Her-2/neu gene amplification as predictive factors of response to trastuzumab in patients with HER-2 overexpressing metastatic breast cancer (MBC).

AIM: Trastuzumab (T), a humanised monoclonal antibody against HER-2, is active in HER-2-positive MBC patients. However, nearly 60% of the patients do not benefit from T, stressing the need for additional predictive markers. The following markers could be implicated in response to T: (1) the magnitude of Her-2 gene amplification; (2) the co-expression of the other HER family receptors, possibly responsible for HER-2 trans-activation; (3) the activated status of HER-2; (4) the activated status of downstream effectors as mitogen-activated protein kinases (MAPKs), p38 and p27. METHODS: Medical files of patients with MBC treated with T either as a single agent or in combination with chemotherapy (CT) were reviewed. HER family members (EGFR, HER-2, HER-3, HER-4), the phosphorylated forms of EGFR (p-EGFR), HER-2 (p-HER-2) and of the downstream effectors were evaluated in the archival tumours. The correlation between clinical outcome and the expression of these markers was investigated. RESULTS: (1) Increasing values of Her-2 amplification were associated with a higher probability of achieving an objective response; (2) no statistical significant correlation between the expression of the HER family receptors was found; (3) p-HER-2 was predictive of response in patients treated with T+CT; (4) a statistically significant correlation between p-ERK 1/2, p-p38 and p-HER-2 emerged, pointing to the activated vertical pathway p-HER-2-->p-MAPKs. CONCLUSIONS: p-HER-2 and the magnitude of Her-2 amplification were predictive of response to T and their role deserves to be analysed in larger and more homogenous T-treated populations such as those from large phase III trials.

A phase II study of sabarubicin (MEN-10755) as second line therapy in patients with locally advanced or metastatic platinum/taxane resistant ovarian cancer.

BACKGROUND: Sabarubicin (MEN-10755) is a third generation anthracycline, with a remarkable antitumor activity in human tumor xenografts, including doxorubicin-resistant tumors. Phase I studies have shown that myelosuppression is the main toxicity of sabarubicin, while its cumulative cardiotoxicity is mild. METHODS: The aim of the study was to evaluate the activity and safety profile of sabarubicin in patients with locally advanced or metastatic ovarian cancer failing 1st line platinum and/or taxane based chemotherapy, and relapsing earlier than 6 months after the last chemotherapy. Eligible patients received sabarubicin at the dose of 80 mg/m2 (dose level 0) every 3 weeks over 30 minutes. Dose was to be escalated to 90 mg/m2 (dose level +1) after the 1st cycle in case of grade 0-1 toxicity, while it was to be reduced to 60 mg/m2 (dose level -1) in case of toxicity. Response was assessed every 2 courses according to WHO criteria. Toxicity was graded according to Common Toxicity Criteria version 2.0. Gehan's design was used for sample size determination. RESULTS: Nineteen patients were enrolled and received 65 courses. One patient had a confirmed partial response, 9 patients had stable disease, 5 patients had disease progression, 3 patients were not evaluable for response, while one patient had an early progressive disease. The duration of response was 88 days. Mean time to disease progression was 125 days (range 56-188). Median survival was 62 days (range 36-202). Hematologic toxicity was moderate, since grade 3-4 neutropenia was observed in 25 out of 52 courses at 80 mg/m2, and grade 4 neutropenia occurred in one out of 12 courses at 90 mg/m2. Other grade 3-4 toxicities were: fatigue (five cases), nausea (two cases), stomatitis, general health deterioration, anorexia, vomiting, abdominal pain, hyponatremia (one case each). Cardiac toxicity was observed in the study; in fact, left ventricular ejection fraction (LVEF) fell below 50% in 2 patients, and 3 patients had a >15% decrease of LVEF from baseline, but there were no signs/symptoms of congestive heart failure. CONCLUSIONS: Sabarubicin showed limited activity in patients with resistant ovarian cancer. However, the observed data on disease stabilization, together with the drug's overall manageable toxicity profile, may prompt to its further investigation in advanced ovarian cancer.