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1.
Osteoporos Int ; 32(3): 473-482, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32886189

ABSTRACT

A 12-month exercise program reversibly prevented hip bone loss in premenopausal women with early breast cancer. The bone-protective effect was maintained for 2 years after the end of the program but was lost thereafter. PURPOSE: Breast cancer survivors are at an increased risk for osteoporosis and fracture. This 5-year follow-up of a randomized impact exercise intervention trial evaluated the maintenance of training effects on bone among breast cancer patients. METHODS: Five hundred seventy-three early breast cancer patients aged 35-68 years and treated with adjuvant therapy were allocated into a 12-month exercise program or a control group. Four hundred forty-four patients (77%) were included in the 5-year analysis. The exercise intervention comprised weekly supervised step aerobics, circuit exercises, and home training. Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry. Physical activity was estimated in metabolic equivalent (MET) hours per week and physical performance assessed by 2-km walking and figure-8 running tests. RESULTS: In premenopausal patients, the 12-month exercise program maintained femoral neck (FN) and total hip (TH) aBMD for 3 years, but the protective effect was lost thereafter. The mean FN aBMD change in the exercise and control groups was - 0.2% and - 1.5% 1 year, - 1.1% and - 2.1% 3 years and - 3.3% versus - 2.4% 5 years after the beginning of the intervention, respectively. Lumbar spine (LS) bone loss was not prevented in premenopausal women and no training effects on aBMD were seen in postmenopausal women. The main confounding element of the study was the unexpected rise in physical activity among patients in the control group. The physical performance improved among premenopausal women in the exercise group compared with the controls. CONCLUSION: The 12-month exercise program prevented FN and TH bone loss in premenopausal breast cancer patients for 3 years. The bone-protective effect was reversible and lost thereafter.


Subject(s)
Bone Density , Breast Neoplasms , Absorptiometry, Photon , Adult , Aged , Breast Neoplasms/therapy , Female , Femur Neck , Follow-Up Studies , Humans , Middle Aged
2.
Diagn Interv Imaging ; 100(11): 699-708, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31257114

ABSTRACT

PURPOSE: To evaluate the utility of multi-parametric magnetic resonance imaging (MP-MRI), including dynamic contrast-enhanced MRI and diffusion-weighted MRI, for monitoring tumor tissue changes after volumetric-modulated arc radiotherapy in localized prostate cancer (PCa), and to compare the radiotherapy induced tumor tissue changes between conventional, moderate and extreme hypofractionated groups. Furthermore, we aimed to evaluate if follow-up by MRI has an incremental value compared to the standard care by prostate-specific antigen (PSA) serum level measurement. MATERIALS AND METHODS: Fifty-five men (mean age: 70±5 [SD] years; range: 60-79 years) with biopsy-proven PCa underwent MRI examination before radiotherapy, and at 3 and 12 months after radiotherapy. Pharmacokinetic analysis post-processing platform with dedicated software (Tissue 4D) was used to generate colorized parametric maps of enhancing tumors. The volume transfer constant (Ktrans), reflux constant (Kep), and initial area under curve (iAUC) were calculated from the tumors. Tumor apparent diffusion coefficient (ADC) value was measured on the ADC map. The patients were allocated into three radiotherapy groups: 17 conventional (39×2Gy), 16 moderate (20×3Gy) and 22 extreme hypofractionated (5×7.25Gy) regimen. RESULTS: Sixty lesions were detected in the prostates of the 55 patients. Follow-up MRI showed decreases in tumor size and degree of enhancement. Ktrans, Kep, and iAUC all decreased at 3 months (P<0.001, respectively) and decreased further at 12 months (P<0.001, respectively). ADC increased at 3 months (P<0.001) and increased further at 12 months (P<0.001). There were no significant differences in the percentage changes of the measured MP-MRI parameters of the tumors from baseline to 12 months between the conventional, moderate and extreme hypofractionated regimen groups. CONCLUSION: MP-MRI is a reliable tool for lesion detection and follow-up, providing both qualitative and quantitative data.


Subject(s)
Multiparametric Magnetic Resonance Imaging/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated/methods , Aged , Area Under Curve , Contrast Media , Humans , Male , Middle Aged , Neoplasm Grading , Prospective Studies , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Radiation Dose Hypofractionation , Radiation Monitoring/methods , Tumor Burden/radiation effects
3.
Eur J Cancer ; 115: 27-36, 2019 07.
Article in English | MEDLINE | ID: mdl-31082690

ABSTRACT

BACKGROUND: Testicular lymphoma is a rare malignancy affecting mainly elderly men, the majority representing diffuse large B-cell lymphoma (DLBCL). Its relapse rate is higher than that of nodal DLBCL, often affecting the central nervous system (CNS) with dismal prognosis. PATIENTS AND METHODS: We searched for patients with testicular DLBCL (T-DLBCL) involvement from the pathology databases of Southern Finland University Hospitals and the Danish Lymphoma Registry. Clinical information was collected, and outcomes between treatment modalities were evaluated. Progression-free survival (PFS), disease-specific survival (DSS) and overall survival (OS) were assessed using Kaplan-Meier and Cox proportional hazards methods. RESULTS: We identified 235 patients; of whom, 192 were treated with curative anthracycline-based chemotherapy. Full survival data were available for 189 patients. In univariate analysis, intravenous CNS-directed chemotherapy, and irradiation or orchiectomy of the contralateral testis translated into favourable PFS, DSS and OS, particularly among the elderly patients (each p ≤ 0.023). Intrathecal chemotherapy had no impact outcome. In multivariate analyses, the advantage of intravenous CNS-directed chemotherapy (hazard ration [HR] for OS, 0.419; 95% confidence interval [CI], 0.256-0.686; p = 0.001) and prophylactic treatment of contralateral testis (HR for OS, 0.514; 95% CI, 0.338-0.782; p = 0.002) was maintained. Rituximab improved survival only among high-risk patients (International Prognostic Index≥3, p = 0.019). The cumulative risk of CNS progression was 8.4% and did not differ between treatment modalities. CONCLUSION: The results support the use of CNS-directed chemotherapy and prophylactic treatment of the contralateral testis in patients with T-DLBCL involvement. Survival benefit appears resulting from better control of systemic disease rather than prevention of CNS progression.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Central Nervous System Neoplasms/prevention & control , Lymphoma, Large B-Cell, Diffuse/drug therapy , Testicular Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Central Nervous System Neoplasms/mortality , Central Nervous System Neoplasms/secondary , Databases, Factual , Denmark , Disease Progression , Finland , Humans , Infusions, Intravenous , Infusions, Spinal , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/radiotherapy , Male , Middle Aged , Orchiectomy , Progression-Free Survival , Registries , Risk Assessment , Risk Factors , Testicular Neoplasms/mortality , Testicular Neoplasms/pathology , Testicular Neoplasms/radiotherapy , Time Factors
4.
Diagn Interv Imaging ; 98(1): 63-71, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27687831

ABSTRACT

OBJECTIVES: To investigate whether diffusion-weighted imaging (DWI) apparent diffusion coefficient (ADC) correlates with prostate cancer aggressiveness and further to compare the diagnostic performance of ADC and normalized ADC (nADC: normalized to non-tumor tissue). PATIENTS AND METHODS: Thirty pre-treatment patients (mean age, 69years; range: 59-78years) with prostate cancer underwent magnetic resonance imaging (MRI) examination, including DWI with three b values: 50, 400, and 800s/mm2. Both ADC and nADC were correlated with the Gleason score obtained through transrectal ultrasound-guided biopsy. RESULTS: The tumor minimum ADC (ADCmin: the lowest ADC value within tumor) had an inverse correlation with the Gleason score (r=-0.43, P<0.05), and it was lower in patients with Gleason score 3+4 than in those with Gleason score 3+3 (0.54±0.11×103mm2/s vs. 0.64±0.12×10-3mm2/s, P<0.05). Both the nADCmin and nADCmean correlated with the Gleason score (r=-0.52 and r=-0.55, P<0.01; respectively), and they were lower in patients with Gleason score 3+4 than those with Gleason score 3+3 (P<0.01; respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.765, 0.818, or 0.833 for the ADCmin, nADCmin, or nADCmean; respectively, in differentiating between Gleason score 3+4 and 3+3 tumors. CONCLUSION: Tumor ADCmin, nADCmin, and nADCmean are useful markers to predict the aggressiveness of prostate cancer.


Subject(s)
Adenocarcinoma/diagnostic imaging , Diffusion Magnetic Resonance Imaging , Prostatic Neoplasms/diagnostic imaging , Adenocarcinoma/pathology , Aged , Humans , Image-Guided Biopsy , Male , Middle Aged , Prospective Studies , Prostate-Specific Antigen/blood , Prostatic Neoplasms/pathology , Ultrasonography, Interventional
5.
Ann Oncol ; 25(8): 1544-50, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24608200

ABSTRACT

BACKGROUND: We have previously shown the prognostic importance of tumor-infiltrating lymphocytes (TILs) in newly diagnosed triple-negative breast cancer (TNBC) using tumor samples from a large clinical trial cohort. In this study, we aimed to validate these findings and also investigate associations with trastuzumab benefit in HER2-overexpressing disease (HER2+). PATIENTS AND METHODS: A prospective-retrospective study was conducted using samples from the FinHER adjuvant, phase III trial that enrolled 1010 early-stage BC patients, 778 of whom were HER2-nonamplified. Those with HER2+ disease (n = 232) were randomized to 9 weeks of trastuzumab or no trastuzumab in addition to chemotherapy. Two pathologists independently quantified stromal TILs in 935 (92.6%) available slides. The primary end point of distant disease-free survival (DDFS) and interactions with trastuzumab were studied in Cox regression models. RESULTS: Confirming our previous findings, in TNBC (n = 134) each 10% increase in TILs was significantly associated with decreased distant recurrence in TNBC; for DDFS the hazard ratio adjusted for clinicopathological factors: 0.77; 95% confidence interval (CI) 0.61-0.98, P = 0.02. In HER2+ BC (n = 209), each 10% increase in lymphocytic infiltration was significantly associated with decreased distant recurrence in patients randomized to the trastuzumab arm (DDFS P interaction = 0.025). CONCLUSIONS: Higher levels of TILs present at diagnosis were significantly associated with decreased distant recurrence rates in primary TNBC. These results confirm our previous data and further support that TILs should be considered as a robust prognostic factor in this BC subtype. We also report for the first time an association between higher levels of TILs and increased trastuzumab benefit in HER2+ disease. Further research into why some TN and HER2+ BCs can or cannot generate a host antitumor immune response and how trastuzumab can favorably alter the immune microenvironment is warranted.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Pharmacological , Biomarkers, Tumor , Lymphocytes, Tumor-Infiltrating/pathology , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/immunology , Adult , Aged , Biomarkers, Pharmacological/analysis , Biomarkers, Tumor/analysis , Chemotherapy, Adjuvant , Female , Finland , Humans , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prognosis , Trastuzumab , Treatment Outcome , Triple Negative Breast Neoplasms/diagnosis , Triple Negative Breast Neoplasms/pathology
6.
Eur J Cancer Care (Engl) ; 23(2): 274-83, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24237363

ABSTRACT

The purpose of this study was to evaluate prospectively the quality of life (QOL) and received social support from the network and nurses in significant others of breast cancer patients and identify factors predicting negative changes in their QOL within 6 months. The quasi-random longitudinal study conducted for the breast cancer patients and their significant others. Patients were quasi-randomised to supportive intervention group (via telephone at baseline and face-to-face at follow-up) and control group. This paper reports results of significant others (N = 165). The QOL data were collected using the Quality of Life Index - Cancer Version (QLI-CV). Support from network in aid increased the risk of negative changes in health and functioning. Retired significant others had a greater risk of more negative changes in their global and in socio-economic QOL than other. Relatives had a smaller risk to negative changes both in their global and in their family QOL than spouses/partners/boyfriends of patients with breast cancer. QOL of the significant others should be supported more intensively and enhanced by the use of individually tailored methods on the basis of significant others and their family needs.


Subject(s)
Breast Neoplasms , Quality of Life/psychology , Social Support , Spouses/psychology , Adolescent , Adult , Aged , Female , Humans , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Telephone , Young Adult
7.
J Clin Pathol ; 66(12): 1046-50, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23863219

ABSTRACT

BACKGROUND AND AIMS: The most commonly used diagnostic method for the preoperative diagnosis of thyroid nodules is ultrasound-guided fine-needle aspiration biopsy (FNA), which often yields non-diagnostic or non-definitive results and seldom produces definite malignant diagnoses. To improve upon the malignancy-specific sensitivity, we tested core needle biopsies (CNBs) of thyroid lesions taken from surgical specimens. MATERIAL AND METHODS: 52 consecutive patients with malignant or malignant-suspicious thyroid nodules were referred to Tampere University Hospital between May 2010 and December 2011. Preoperative FNAs were categorised as follicular neoplasm (48%), suspicion for malignancy (46%) or malignancy (6%). Intraoperative FNA and CNB samples were acquired from surgical specimens removed during surgery. The results of the needle biopsies were compared with the final pathological diagnosis. RESULTS: CNBs had a high definitive sensitivity for malignancy (61%, CI 41% to 78%) whereas the definitive sensitivity for malignancy of FNAs was significantly lower (22%, CI 10% to 42%). CNB was not beneficial in the diagnosis of follicular thyroid lesions. When all suspected follicular tumours were excluded, the definitive sensitivity of CNB rose to 70% (CI 48% to 86%). CONCLUSIONS: CNB may be beneficial for the diagnosis of papillary thyroid carcinoma and other non-follicular thyroid lesions. CNB may be considered as an additional diagnostic procedure in cases with FNA suspicious for malignancy.


Subject(s)
Biopsy, Fine-Needle/standards , Biopsy, Large-Core Needle/standards , Carcinoma/diagnosis , Thyroid Neoplasms/diagnosis , Thyroid Nodule/diagnosis , Adult , Aged , Carcinoma/pathology , Carcinoma/surgery , Carcinoma, Papillary , Female , Finland , Hospitals, University , Humans , Intraoperative Period , Male , Middle Aged , Prospective Studies , Sensitivity and Specificity , Thyroid Cancer, Papillary , Thyroid Gland/pathology , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Thyroid Nodule/pathology , Thyroid Nodule/surgery
8.
Scand J Surg ; 101(4): 301-6, 2012.
Article in English | MEDLINE | ID: mdl-23238509

ABSTRACT

BACKGROUND: The aim of this study was to investigate trends in the incidence, diagnostics, treatment and survival of thyroid cancer in Tampere University Hospital (TAUH) region in recent decades. MATERIAL AND METHODS: New thyroid cancer cases from 1981 to 2002 were ascertained from the Finnish Cancer Registry. Follow-up data was collected from medical records of TAUH. Differentiated thyroid cancer (DTC; consisting of papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC)) patients' data was analyzed and divided into two equal time periods (1981-1991 and 1992-2002). RESULTS: The total amount of thyroid cancer cases was 553, of which 427 (77%) were papillary and 72 (13%) follicular. Thyroid cancer was four times more common in females than in males and the median age at the time of diagnosis was 52 years. The incidence of DTC was 4.5/100,000 in the earlier group and 6.0/100,000 in the later group (IRR 1.33, CI 1.11-1.60). The proportion of papillary thyroid cancer rose from 81% to 89% (p=0.02) in two study periods. Median tumour size became smaller, from 25 mm to 15 mm (p<0.001). Surgery became more radical as total thyroidectomies were performed almost exclusively on the later group (p<0.001). Median cumulative dose of radioiodine (I131) therapy was higher in the later group (p=0.04). There was no difference in number of cancer recurrences (p=0.54). The prognosis of DTC was good; 10-year disease-specific survival was 92% in the earlier group and 94% in the later group (p=0.43). CONCLUSIONS: The incidence of thyroid cancer has risen and proportion of papillary cancer has increased, however, median size of tumour has decreased. No difference was seen in either all-cause or disease-specific survival.


Subject(s)
Carcinoma/epidemiology , Thyroid Neoplasms/epidemiology , Carcinoma/mortality , Carcinoma/pathology , Carcinoma/therapy , Carcinoma, Papillary , Female , Finland/epidemiology , Humans , Incidence , Iodine Radioisotopes/therapeutic use , Kaplan-Meier Estimate , Male , Middle Aged , Radiopharmaceuticals/therapeutic use , Registries , Retrospective Studies , Survival Rate , Thyroid Cancer, Papillary , Thyroid Neoplasms/mortality , Thyroid Neoplasms/pathology , Thyroid Neoplasms/therapy , Thyroidectomy , Treatment Outcome , Tumor Burden
9.
J Musculoskelet Neuronal Interact ; 12(3): 127-35, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22947544

ABSTRACT

In this 12-month RCT, we examined whether aerobic impact exercise training (3x/week) could facilitate breast cancer survivors' recovery by enhancing their bone structural strength, physical performance and body composition. After the adjuvant chemo- and/ or radiotherapy, 86 patients were randomly assigned into the training or control group. Structural bone traits were assessed with pQCT at the tibia and with DXA at the femoral neck. Agility (figure-8 running), jump force and power (force platform), grip strength and cardiovascular fitness (2-km walk test) were also assessed. Training effects on outcome variables were estimated by two-way factorial ANCOVA using the study group and menopausal status as fixed factors. Bone structural strength was better maintained among the trainees. At the femoral neck, there was a small but significant 2% training effect in the bone mass distribution (p=0.05). At the tibial diaphysis, slight 1% to 2% training effects (p=0.03) in total cross-sectional area and bone structural strength were observed (p=0.03) among the postmenopausal trainees. Also, 3% to 4% training effects were observed in the figure-8 running time (p=0.03) and grip strength (p=0.01). In conclusion, vigorous aerobic impact exercise training has potential to maintain bone structural strength and improve physical performance among breast cancer survivors.


Subject(s)
Bone and Bones/physiology , Breast Neoplasms/rehabilitation , Exercise Therapy/methods , Physical Fitness/physiology , Absorptiometry, Photon , Adult , Aged , Bone Density , Bone and Bones/anatomy & histology , Female , Humans , Middle Aged , Survivors
10.
Prostate Cancer Prostatic Dis ; 15(3): 303-7, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22546837

ABSTRACT

BACKGROUND: Radical radiotherapy (RT) combined with androgen deprivation therapy is currently the standard treatment for elderly patients with localized intermediate- or high-risk prostate cancer (PC). To increase the recurrence-free and overall survival, we conducted an adjuvant, randomized trial using docetaxel (T) in PC patients (Scandinavian Prostate Cancer Group trial 13). METHODS: The inclusion criteria are the following: men >18 and ≤75 years of age, WHO/ECOG performance status 0--1, histologically proven PC within 12 months before randomization and one of the following: T2, Gleason 7 (4+3), PSA >10; T2, Gleason 8--10, any PSA; or any T3 tumors. Neoadjuvant/adjuvant hormone therapy is mandatory for all patients. The patients were randomized to receive six cycles of T (75 mgm(-2) d 1. cycle 21 d) or no docetaxel after radical RT (with a minimum tumor dose of 74 Gy). This study identifier number is NTC 006653848 (http://www.clinicaltrials.org). RESULTS: In this preplanned safety analysis of 100 patients, T treatment induced grade (G) 3 adverse events (AEs) in 15 patients (30%) and G4 AEs in 30 patients (60%), mainly due to bone marrow toxicity. Neutropenia G3--4 was observed in 72% of the patients, febrile neutropenia was found in 24% of patients, neutropenic infection in 10% of patients and G3 infection without neutropenia in 4% of patients. Nonhematological G3 AEs were rare: anorexia, diarrhea, mucositis, nausea, pain (1 patient each) and fatigue (5). Other severe serious AEs related to T were pulmonary embolism and renal failure. However, only three patients discontinued T before completing the planned six cycles. No deaths had occurred. No patients in the control arm experienced G3--4 toxicities at 12 weeks after the randomization. CONCLUSIONS: Adjuvant docetaxel chemotherapy after radiotherapy has a higher frequency of neutropenia than previous studies on patients with metastatic disease. Otherwise, the treatment was quite well tolerated.


Subject(s)
Antineoplastic Agents/adverse effects , Prostatic Neoplasms/drug therapy , Taxoids/adverse effects , Aged , Antineoplastic Agents/therapeutic use , Chemotherapy, Adjuvant , Combined Modality Therapy , Docetaxel , Gonadotropin-Releasing Hormone/analogs & derivatives , Gonadotropin-Releasing Hormone/therapeutic use , Humans , Male , Middle Aged , Neoplasm Staging , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Taxoids/therapeutic use
11.
Osteoporos Int ; 23(5): 1601-12, 2012 May.
Article in English | MEDLINE | ID: mdl-21892676

ABSTRACT

UNLABELLED: The ability of combined step aerobic- and circuit-training to prevent bone loss after breast cancer treatments was related to skeletal site and patients' menopausal status. Among premenopausal breast cancer survivors, a 12-month exercise intervention completely prevented bone loss at the femoral neck, whereas no exercise effect was seen at lumbar spine or at neither site in postmenopausal women. INTRODUCTION: The primary objective of this randomised clinical trial was to determine the preventive effect of supervised weight-bearing jumping exercises and circuit training on bone loss among breast cancer patients. METHODS: Of 573 breast cancer survivors aged 35-68 years randomly allocated into exercise or control group after adjuvant treatments, 498 (87%) were included in the final analysis. The 12-month exercise intervention comprised weekly supervised step aerobic- and circuit-exercises and similar home training. Bone mineral density (BMD) at lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry. Physical performance was assessed by 2-km walking and figure-8 running tests, and the amount of physical activity was estimated in metabolic equivalent-hours/week. RESULTS: In premenopausal women, bone loss at the femoral neck was prevented by exercise, the mean BMD changes being -0.2% among the trainees vs. -1.4% among the controls (p = 0.01). Lumbar bone loss could not be prevented (-1.9% vs. -2.2%). In postmenopausal women, no significant exercise-effect on BMD was found either at the lumbar spine (-1.6% vs. -2.1%) or femoral neck (-1.1% vs. -1.1%). CONCLUSIONS: This 12-month aerobic jumping and circuit training intervention completely prevented femoral neck bone loss in premenopausal breast cancer patients, whereas no effect on BMD was seen in postmenopausal women.


Subject(s)
Bone Density/physiology , Breast Neoplasms/therapy , Exercise Therapy/methods , Osteoporosis/prevention & control , Adult , Aged , Body Composition , Body Weight/physiology , Breast Neoplasms/physiopathology , Chemotherapy, Adjuvant/adverse effects , Female , Femur Neck/physiopathology , Humans , Lumbar Vertebrae/physiopathology , Middle Aged , Motor Activity/physiology , Osteoporosis/etiology , Osteoporosis/physiopathology , Patient Compliance , Postmenopause/physiology , Premenopause/physiology , Single-Blind Method
12.
Ann Oncol ; 22(9): 2007-2013, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21285132

ABSTRACT

BACKGROUND: It is unknown how a very high tumor total HER2 (human epidermal growth factor receptor-2) content (H2T) influences outcome in early breast cancer treated with adjuvant trastuzumab plus chemotherapy. PATIENTS AND METHODS: H2T was measured using a novel quantitative assay (HERmark(®)) from formalin-fixed tumor tissue of 899 women who participated in the FinHer trial (ISRCTN76560285). In a chromogenic in situ hybridization (CISH) test, 197 (21.9%) patients had HER2-positive cancer and were randomly assigned to receive trastuzumab or control. RESULTS: Cancer H2T levels varied 1808-fold. High H2T levels were correlated with a positive HER2 status by CISH (P < 0.0001). A nonlinear association was present between H2T and the hazard of distant recurrence in a subpopulation treatment effect pattern plot analysis in CISH-positive disease. Patients with very high H2T (defined by ≥22-fold the median of HER2-negative cancers; 13% of CISH-positive cancers) did not benefit from adjuvant trastuzumab [hazard ratio (HR) 1.23; 95% confidence interval (CI) 0.33-4.62; P = 0.75], whereas the rest of the patients with HER2-positive disease by CISH (87%) did benefit (HR 0.52; 95% CI 0.28-1.00; P = 0.050). CONCLUSION: Patients with HER2-positive breast cancer with very high tumor HER2 content may benefit less from adjuvant trastuzumab compared with those whose cancer has more moderate HER2 content.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Breast Neoplasms/enzymology , Receptor, ErbB-2/biosynthesis , Adult , Aged , Breast Neoplasms/genetics , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Docetaxel , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Immunohistochemistry , In Situ Hybridization , Middle Aged , Receptor, ErbB-2/genetics , Taxoids/administration & dosage , Trastuzumab , Treatment Outcome , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine
13.
Eur J Clin Microbiol Infect Dis ; 30(2): 233-41, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20938703

ABSTRACT

The purpose of this study was to examine the association between bacterial colonization/infection and respiratory outcomes in children younger than 3 years old who were hospitalized for their first wheezing episode. This was an observational study. The primary outcome was hospitalization time and the secondary outcomes included relapses within 2 months and time to recurrent wheezing (i.e. three physician confirmed wheezing episodes) within 12 months. Bacterial antibody assays for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae and Chlamydia pneumoniae were studied as well as nasopharyngeal bacterial culture for the three former and urine pneumococcal antigen. Nasopharyngeal bacterial culture was positive in 31/52 (60%) children, serologic evidence of bacterial infection was found in 17/96 (18%) children, urine pneumococcal antigen was positive in 24/101 (24%), and any bacterial detection method was positive in 53/106 (50%) children. The children with positive nasopharyngeal bacterial culture had longer duration of hospitalization (hazard ratio 2.4) and more often relapsed within two months than those with negative culture (odds ratio 7.3). In this study, half of the first time wheezing children had bacterial colonization or symptomatic or asymptomatic bacterial infection. The bacterial colonization (i.e. positive nasopharyngeal bacterial culture) was associated with longer duration of hospitalization and higher risk of recurrent wheezing.


Subject(s)
Bacterial Infections/microbiology , Carrier State/microbiology , Nasopharynx/microbiology , Respiratory Sounds , Antibodies, Bacterial/blood , Bacteria/isolation & purification , Bacterial Infections/epidemiology , Carrier State/epidemiology , Child, Preschool , Female , Hospitalization , Humans , Infant , Length of Stay , Male , Recurrence , Risk Assessment
14.
Psychooncology ; 20(11): 1211-20, 2011 Nov.
Article in English | MEDLINE | ID: mdl-20878646

ABSTRACT

OBJECTIVE: The study aimed at investigating the quality of life (QoL) and physical performance and activity, and their interrelations, in Finnish female breast cancer patients shortly after adjuvant treatments. METHODS: A total of 537 disease-free breast cancer survivors aged 35-68 years were surveyed at the beginning of a one year randomized exercise intervention. The patients were interviewed using EORTC QLQ-C30, FACIT-F, RBDI, and WHQ (for vasomotor symptoms) questionnaires. Physical performance was tested by a 2 km walking test. Physical activity was measured by a questionnaire and a prospective two-week diary. Multivariate analysis was used to study the factors associated with QoL. RESULTS: About 26% of the patients were rated as depressed, 20.4% as fatigued, and 82% suffered from menopausal symptoms. The global QoL was lower than in general population (69.4 vs 74.7, p<0.001). About 62% of the walking test results were below the population average. Fatigue (p<0.001), depression (p<0.001), body mass index (p = 0.016) and comorbidity (p = 0.032) impaired, and physical activity (p = 0.003) improved QoL. Physical activity level correlated positively to physical performance (r = -0.274, p<0.0001). CONCLUSIONS: The QoL of the patients shortly after adjuvant treatments was impaired and the physical performance poor as compared to general population. In particular, depression and fatigue were related to impaired QoL. Physical performance and activity level were the only factors that correlated positively to QoL. Thus, physical exercise could be useful in rehabilitation of cancer survivors, especially for depressed and fatigued patients.


Subject(s)
Breast Neoplasms/psychology , Exercise Therapy , Quality of Life/psychology , Adult , Aged , Breast Neoplasms/therapy , Chemotherapy, Adjuvant/psychology , Depression/etiology , Depression/prevention & control , Exercise Therapy/psychology , Fatigue/etiology , Fatigue/prevention & control , Female , Humans , Menopause/psychology , Middle Aged , Motor Activity , Physical Fitness/psychology , Surveys and Questionnaires
15.
Eur J Clin Microbiol Infect Dis ; 30(3): 387-92, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20981463

ABSTRACT

Diagnosing influenza at an early stage of illness is important for the initiation of effective antiviral treatment. However, especially in young children, influenza often commences with an abrupt onset of fever, with full-blown respiratory symptoms developing only later. We determined the feasibility of diagnosing influenza in young children already during the first signs of the illness. During confirmed influenza activity, we obtained nasal swabs from children aged 1-3 years who presented as outpatients within 24 hours of the onset of fever (≥38.0°C). The specimens were tested for influenza viruses with viral culture, antigen detection, PCR, and a rapid point-of-care test (Actim Influenza A&B, Medix Biochemica, Finland). In addition, follow-up specimens were obtained from a proportion of children 3-7 days later. Influenza virus was detected already within 24 hours of symptom onset in 56 of 61 (92%; 95% CI 82-97%) children in whom influenza was eventually confirmed in the laboratory. A total of 158 rapid tests performed within 24 hours of symptom onset yielded a sensitivity of 90% (95% CI 74-98%) for influenza A viruses but only 25% (95% CI 3-61%) for influenza B viruses (P < 0.001), resulting in an overall sensitivity of 77% (95% CI 61-89%) and specificity of 99% (95% CI 95-100%) for all influenza viruses. In most young children, influenza can already be accurately diagnosed within 24 hours of symptom onset. The rapid point-of-care test used was sensitive and specific for diagnosing influenza A, but its sensitivity for influenza B was limited.


Subject(s)
Influenza A virus/isolation & purification , Influenza B virus/isolation & purification , Influenza, Human/diagnosis , Influenza, Human/drug therapy , Antigens, Viral/analysis , Antiviral Agents/therapeutic use , Child, Preschool , Early Diagnosis , Feasibility Studies , Fluoroimmunoassay , Humans , Infant , Influenza A virus/genetics , Influenza B virus/genetics , Influenza, Human/virology , Oseltamivir/therapeutic use , Point-of-Care Systems , Polymerase Chain Reaction , Reagent Kits, Diagnostic , Sensitivity and Specificity , Zanamivir/therapeutic use
16.
Ann Oncol ; 21(5): 968-73, 2010 May.
Article in English | MEDLINE | ID: mdl-19819914

ABSTRACT

BACKGROUND: Alternating administration of docetaxel and gemcitabine might result in improved time-to-treatment failure (TTF) and fewer adverse events compared with single-agent docetaxel as treatment of advanced breast cancer. PATIENTS AND METHODS: Women diagnosed with advanced breast cancer were randomly allocated to receive 3-weekly docetaxel (group D) or 3-weekly docetaxel alternating with 3-weekly gemcitabine (group D/G) until treatment failure as first-line chemotherapy. The primary end point was TTF. RESULTS: Two hundred and thirty-seven subjects were assigned to treatment (group D, 115; group D/G, 122). The median TTF was 5.6 and 6.2 months in groups D and D/G, respectively (hazard ratio 0.85, 95% confidence interval 0.63-1.16; P = 0.31). There was no significant difference in time-to-disease progression, survival, and response rate between the groups. When adverse events were evaluated for the worst toxicity encountered during treatment, there was little difference between the groups, but when they were assessed per cycle, alternating treatment was associated with fewer severe (grade 3 or 4) adverse effects (P = 0.013), and the difference was highly significant for cycles when gemcitabine was administered in group D/G (P < 0.001). CONCLUSION: The alternating regimen was associated with a similar TTF as single-agent docetaxel but with fewer adverse effects during gemcitabine cycles.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Lobular/drug therapy , Adult , Aged , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/secondary , Carcinoma, Lobular/metabolism , Carcinoma, Lobular/secondary , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Docetaxel , Female , Humans , Immunoenzyme Techniques , Middle Aged , Neoplasm Invasiveness , Neoplasm Metastasis , Prospective Studies , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Survival Rate , Taxoids/administration & dosage , Treatment Outcome , Gemcitabine
17.
Phys Rev Lett ; 102(12): 126807, 2009 Mar 27.
Article in English | MEDLINE | ID: mdl-19392310

ABSTRACT

We present a density-functional-theory study of transition-metal atoms (Sc-Zn, Pt, and Au) embedded in single and double vacancies (SV and DV) in a graphene sheet. We show that for most metals, the bonding is strong and the metal-vacancy complexes exhibit interesting magnetic behavior. In particular, an Fe atom on a SV is not magnetic, while the Fe@DV complex has a high magnetic moment. Surprisingly, Au and Cu atoms at SV are magnetic. Both bond strengths and magnetic moments can be understood within a simple local-orbital picture, involving carbon sp(2) hybrids and the metal spd orbitals. We further calculate the barriers for impurity-atom migration, and they agree well with available experimental data. We discuss the experimental realization of such systems in the context of spintronics and nanocatalysis.

19.
Comput Biol Med ; 38(4): 519-24, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18342845

ABSTRACT

The aim here is to show that texture parameters of magnetic resonance imaging (MRI) data changes in lymphoma tissue during chemotherapy. Ten patients having non-Hodgkin lymphoma masses in the abdomen were imaged for chemotherapy response evaluation three consecutive times. The analysis was performed with MaZda texture analysis (TA) application. The best discrimination in lymphoma MRI texture was obtained within T2-weighted images between the pre-treatment and the second response evaluation stage. TA proved to be a promising quantitative means of representing lymphoma tissue changes during medication follow-up.


Subject(s)
Abdominal Neoplasms/pathology , Image Enhancement , Image Processing, Computer-Assisted , Lymphoma, Non-Hodgkin/pathology , Magnetic Resonance Imaging , Abdominal Neoplasms/drug therapy , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Lymphoma, Non-Hodgkin/drug therapy , Male , Middle Aged , Rituximab , Software , Treatment Outcome
20.
Acta Oncol ; 46(2): 146-52, 2007.
Article in English | MEDLINE | ID: mdl-17453362

ABSTRACT

Based on randomized studies bone-marrow supported (BMS) high-dose chemotherapy (HDCT) is not superior to conventional CT as adjuvant treatment for high-risk breast cancer. To compare the cost-effectiveness of these treatments we examined the data of Finnish patients in the SBG9401 trial 1. Patients were randomized to receive either dose-escalated (de FEC) (group A, n =59) or FEC and HDCT+BMS (group B, n =70). They received adjuvant radiotherapy (RT) + tamoxifen. All direct health care costs of first line treatment at the oncology units were considered as well as productivity costs within the first 3 years of follow-up. Effectiveness was measured by the number of survival days during 5 years of follow-up. The mean direct health care costs were significantly higher in group B (25829 euro in group A vs. 36605 euro in group B, p <0.001), mainly due to a higher number of hospital days. Half of the costs in group A was due to the use of filgrastim (15335 euro in A and 2969 euro in B, p <0.001). The costs of RT were only 5% of total costs. There was no statistically significant difference between the groups in the number of survival days, but sensitivity analysis based on bootstrapping suggested that treatment A would be a less costly and more effective alternative in a great majority of cases.


Subject(s)
Antineoplastic Agents/economics , Antineoplastic Combined Chemotherapy Protocols/economics , Breast Neoplasms/drug therapy , Breast Neoplasms/economics , Granulocyte Colony-Stimulating Factor/economics , Adult , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow/drug effects , Breast Neoplasms/mortality , Chemotherapy, Adjuvant , Cost-Benefit Analysis , Female , Filgrastim , Finland , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Middle Aged , Prospective Studies , Recombinant Proteins , Risk , Survival
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