Bone marrow produces sufficient alloreactive natural killer (NK) cells in vivo to cure mice from subcutaneously and intravascularly injected 4T1 breast cancer.

Purpose: Administration of 5 million alloreactive natural killer (NK) cells after low-dose chemo-irradiation cured mice of 4T1 breast cancer, supposedly dose dependent. We now explored the efficacy of bone marrow as alternative in vivo source of NK cells for anti-breast cancer treatment, as methods for in vitro clinical scale NK cell expansion are still in developmental phases.

Methods: Progression-free survival (PFS) after treatment with different doses of spleen-derived alloreactive NK cells to 4T1-bearing Balb/c mice was measured to determine a dose-response relation.

Long-term update of the 24954 EORTC phase III trial on larynx preservation.

The long-term results of the EORTC 24954 trial comparing sequential versus alternating chemotherapy and radiotherapy (RT) for patients with locally advanced laryngeal and hypopharyngeal cancer are reported. From 1996 to 2004, 450 patients were randomly assigned (1-1) to a sequential arm (SA = induction cisplatin-5fluorouracil followed by a 70Gy-RT for the responders or a total laryngectomy and post-operative RT for the non-responders) and an alternating arm (AA = cisplatin-5fluorouracil alternated with three 2-week courses of 20 Gy-RT for a total dose of 60 Gy). Median follow-up was 10.

An international phase 3 trial in head and neck cancer: quality of life and symptom results: EORTC 24954 on behalf of the EORTC Head and Neck and the EORTC Radiation Oncology Group.

Background: The European Organization for Research and Treatment of Cancer (EORTC) 24954 phase 3 randomized clinical trial compared 2 schemes of combined chemotherapy for patients with resectable cancers of the hypopharynx and larynx: sequential induction chemotherapy and radiotherapy versus alternating chemoradiotherapy. The current study reports detailed effects of both treatment arms on health-related quality of life (HRQOL) and symptoms.

Methods: A total of 450 patients aged 35 years to 76 years (World Health Organization performance status (WHO PS) ≤ 2) with untreated, resectable advanced squamous cell carcinoma of the larynx (tumor classification of T3-T4) or hypopharynx (tumor classification of T2-T3-T4) with regional lymph nodes in the neck classified as N0 to N2 with no metastases were randomized in this prospective phase 3 trial into either the sequential arm (control) or the alternating arm (experimental).

A randomised controlled phase II trial of pre-operative celecoxib treatment reveals anti-tumour transcriptional response in primary breast cancer.

Introduction: Cyclooxygenase-2 (COX-2) is frequently over-expressed in primary breast cancer. In transgenic breast cancer models, over-expression of COX-2 leads to tumour formation while COX-2 inhibition exerts anti-tumour effects in breast cancer cell lines. To further determine the effect of COX-2 inhibition in primary breast cancer, we aimed to identify transcriptional changes in breast cancer tissues of patients treated with the selective COX-2 inhibitor celecoxib.

Randomized, phase III trial of sequential epirubicin and docetaxel versus epirubicin alone in postmenopausal patients with node-positive breast cancer.

Purpose: The Docetaxel Epirubicin Adjuvant (DEVA) trial evaluated the efficacy and toxicity of incorporating docetaxel after epirubicin to create a sequential anthracycline-taxane regimen in early breast cancer.

Patients And Methods: After complete tumor excision, postmenopausal women with node-positive early breast cancer were randomly assigned to either epirubicin 50 mg/m(2) on days 1 and 8 every 4 weeks for six cycles (EPI × 6) or three cycles of epirubicin 50 mg/m(2) on days 1 and 8 every 4 weeks followed by three cycles of docetaxel 100 mg/m(2) on day 1 every 3 weeks (EPI-DOC). A subset of patients also participated in a quality of life (QOL) study.

Elimination of the chemotherapy resistant subpopulation of 4T1 mouse breast cancer by haploidentical NK cells cures the vast majority of mice.

Metastatic breast cancer is currently incurable despite initial responsiveness, assumingly due to the presence of chemoresistant subpopulations that can be characterized as label retaining cells (LRC). In the 4T1 mouse breast cancer model, we previously achieved cure after Cyclophosphamide and Total Body Irradiation (CY + TBI) followed by haploidentical bone marrow and spleen transplantation (BMSPLT). CY + TBI without transplantation induced only transient impaired tumor growth indicating a critical role of donor immune cells.

Economic evaluation of four follow-up strategies after curative treatment for breast cancer: results of an RCT.

Background: An economic evaluation was performed alongside a randomised controlled trial (ISRCTN 74071417) investigating the cost-effectiveness of nurse-led telephone follow-up instead of hospital visits, and of a short educational group programme (EGP) in the first year after breast cancer treatment.

Method: This economic evaluation (n = 299) compared the one-year costs and the effects of four follow-up strategies: (1) hospital follow-up; (2) nurse-led telephone follow-up; (3) hospital follow-up plus EGP; and (4) nurse-led telephone follow-up plus EGP. Costs were measured using cost diaries and hospital registrations.

Nurse-led telephone follow-up and an educational group programme after breast cancer treatment: results of a 2 × 2 randomised controlled trial.

Objective: To investigate whether frequent hospital follow-up in the first year after breast cancer treatment might partly be replaced by nurse-led telephone follow-up without deteriorating health-related quality of life (HRQoL), and whether a short educational group programme (EGP) would enhance HRQoL.

Patients And Methods: A multicentre pragmatic randomised controlled trial (RCT) with a 2×2 factorial design was performed among 320 breast cancer patients who were treated with curative intent. Participants were randomised to follow-up care as usual (3-monthly outpatient clinic visits), nurse-led telephone follow-up, or the former strategies combined with an educational group programme.

Expression of aberrantly glycosylated Mucin-1 in ovarian cancer.

Aims:   Mucin 1 (MUC1) is an important tumour-associated antigen (TAA), both overexpressed and aberrantly glycosylated in adenocarcinomas. The aim of this study was to examine the MUC1-glycosylation status of primary ovarian adenocarcinomas and metastatic lesions.

Methods And Results:   Paraffin-embedded tissue sections of 37 primary ovarian adenocarcinomas representing all histotypes (22 serous, five mucinous, two clear-cell, eight endometrioid), four serous borderline tumours with intraepithelial carcinoma, seven sections of ovarian endometriosis and 13 metastatic lesions were analysed by immunohistochemistry.

Randomized clinical trial on the effects of adenosine 5'-triphosphate infusions on quality of life, functional status, and fatigue in preterminal cancer patients.

Context: One potential agent to improve symptoms and quality of life (QoL) in advanced cancer patients is adenosine 5'-triphosphate (ATP). Several reports suggest that ATP may positively affect QoL and survival in patients with advanced non-small-cell lung cancer.

Objectives: To investigate the effects of ATP infusions on QoL parameters in patients with preterminal cancer of mixed tumor types.

FDG-PET-CT for staging of high-risk breast cancer patients reduces the number of further examinations: A pilot study.

Aim: To determine the additional value of FDG-PET-CT as compared to conventional staging (CS) in high-risk breast cancer patients.

Patients And Methods: Thirty-one high-risk breast cancer patients, 14 of whom had recurrent breast cancer, were included in this study, which took place between June 2005 and March 2008. None of the patients had clinical signs of distant metastases.

Effect of adenosine 5'-triphosphate infusions on the nutritional status and survival of preterminal cancer patients.

The aim of the study was to investigate the effect of intravenous infusions of adenosine 5'-triphosphate (ATP) on nutritional status and survival in preterminal cancer patients. Ninety-nine preterminal cancer patients (estimated life expectancy 1-6 months) with mixed tumor types were randomly allocated to receive either intravenous ATP weekly (8-10 h/week, maximum 50 microg/kg/min) for 8 weeks, or no ATP (control group). Nutritional status parameters were assessed until 8 weeks, and analyzed by repeated-measures analysis of covariance.

[Brain metastases in breast cancer: a special disease course for HER2 positive tumors].

HER2 positive breast cancers are characterized by their aggressive course of disease. Treatment with trastuzumab has significantly improved survival of patients with these cancers. Trastuzumab has few side effects, although in 10-15% of cases it is necessary to interrupt therapy because of cardiotoxicity, in most cases temporarily.

Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy.

Background: Both induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer.

Methods: Patients with resectable advanced squamous cell carcinoma of the larynx (tumor stage T3-T4) or hypopharynx (T2-T4), with regional lymph nodes in the neck staged as N0-N2 and with no metastasis, were randomly assigned to treatment in the sequential (or control) or the alternating (or experimental) arm.

Factors influencing catheter-related infections in the Dutch multicenter study on high-dose chemotherapy followed by peripheral SCT in high-risk breast cancer patients.

Neutropenia following high-dose chemotherapy leads to a high incidence of infectious complications, of which central venous catheter-related infections predominate. Catheter-related infections and associated risk factors in 392 patients participating in a randomized adjuvant breast cancer trial and assigned to receive high-dose chemotherapy and peripheral stem-cell reinfusion were evaluated. Median catheter dwell time was 25 days (range 1-141).

Life-threatening interstitial lung disease associated with trastuzumab: case report.

A female patient with HER2 positive, metastatic breast cancer presented with pulmonary infiltrates, and a plural effusion dyspnoea after several months of trastuzumab treatment. She had been treated without complications with six courses of docetaxel and trastuzumab in combination with dexamethasone with partial remission of disease. Malignancy, infection and cardiomyopathy were excluded as causes of dyspnoea.

Prospective study of long-term impact of adjuvant high-dose and conventional-dose chemotherapy on health-related quality of life.

Purpose: To evaluate and compare health-related quality of life (HRQOL) after conventional- and high-dose adjuvant chemotherapy in patients with high-risk breast cancer.

Patients And Methods: Patients were randomly assigned to either a conventional or high-dose chemotherapy regimen; both regimens were followed by radiotherapy and tamoxifen. HRQOL was evaluated until disease progression using the Short Form-36 (SF-36), Visual Analog Scale, and Rotterdam Symptom Checklist and assessed every 6 months for 5 years after random assignment.

Intravenous ATP infusions can be safely administered in the home setting: a study in pre-terminal cancer patients.

The aim of the study was to investigate the safety of adenosine 5'-triphosphate (ATP) administration at home in pre-terminal cancer patients. Included were patients with cancer for whom medical treatment options were restricted to supportive care, who had a life expectancy of less than 6 months, a World Health Organization performance status 1 or 2, and suffered from at least one of the following complaints: fatigue, anorexia or weight loss >5% over the previous 6 months. Side effects were registered systematically on a standard form according to the National Cancer Institute (NCI) Common Toxicity Criteria.

Follow-up after curative treatment for breast cancer: why do we still adhere to frequent outpatient clinic visits?

Follow-up after curative treatment for breast cancer consists of frequent outpatient clinic visits, scheduled at regular intervals. Its aim is primarily to detect local disease recurrence, or a second primary breast cancer, but also to provide information and psychosocial support. The cost-effectiveness of these frequent visits is being questioned however, leading to a search for less intensive follow-up strategies, such as follow-up by the general practitioner, patient-initiated or nurse-led follow-up or contact by telephone.

Application of adenosine 5'-triphosphate (ATP) infusions in palliative home care: design of a randomized clinical trial.

Background: Palliative care in cancer aims at alleviating the suffering of patients. A previous study in patients with advanced non-small-cell lung cancer showed that adenosine 5'-triphosphate (ATP) infusions had a favourable effect on fatigue, appetite, body weight, muscle strength, functional status and quality of life. The present study was designed 1.

Improving the quality and efficiency of follow-up after curative treatment for breast cancer--rationale and study design of the MaCare trial.

Background: After curative treatment for breast cancer women frequently attend scheduled follow-up examinations. Usually the follow-up is most frequent in the first 2-3 years (2-4 times a year); thereafter the frequency is reduced to once a year in most countries. Its main aim is to detect local disease recurrence, or a second primary breast cancer, but also to provide information and psychosocial support.

Molecular subtypes of breast cancer and amplification of topoisomerase II alpha: predictive role in dose intensive adjuvant chemotherapy.

Benefit from chemotherapy treatment in breast cancer patients is determined by the molecular make-up of the tumour. In a retrospective analysis, we determined the molecular subtypes of breast cancer originally defined by expression microarrays by immunohistochemistry in tumours of patients who took part in a randomised study of adjuvant high-dose chemotherapy in breast cancer. In addition, the topoisomerase II alpha (TOP2A) amplification status was determined by fluorescence in situ hybridisation and chromogenic in situ hybridisation.

Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer.

Background: High-dose chemotherapy in the adjuvant treatment of breast cancer has been abandoned by many.

Patients And Methods: 885 patients with stage III primary breast cancer and four or more axillary lymph node metastases were randomised to receive either five courses of FEC (fluorouracil, epirubicin and cyclophosphamide) followed by radiation therapy and tamoxifen, or the same treatment but with high-dose alkylating chemotherapy (cyclophosphamide, thiotepa and carboplatin) replacing the fifth course of FEC. Of these patients, 621 had HER2/neu-negative disease, as determined by immunohistochemistry and chromogenic in situ hybridisation.

Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy: a longitudinal study.

Purpose: Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.

Patients And Methods: Eight hundred eighty-five patients were randomly assigned between two chemotherapy regimens both followed by radiotherapy and tamoxifen. Fatigue was assessed using vitality scale (score < or = 46 defined as fatigue), poor mental health using mental health scale (score < or = 56 defined as poor mental health) both of Short-Form 36, muscle and joint pain with Rotterdam Symptom Checklist, and Hb levels were assessed before and 1, 2, and 3 years after chemotherapy.