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Joke W. Baars

Bio: Joke W. Baars is an academic researcher from Netherlands Cancer Institute. The author has contributed to research in topics: Chemotherapy & Transplantation. The author has an hindex of 27, co-authored 71 publications receiving 3505 citations. Previous affiliations of Joke W. Baars include Utrecht University & Katholieke Universiteit Leuven.


Papers
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Journal ArticleDOI
TL;DR: Chemotherapy plus involved-field radiotherapy should be the standard treatment for Hodgkin's disease with favorable prognostic features and in patients with unfavorable features, four courses of chemotherapyplus involved- field radiotherapy ought to be thestandard treatment.
Abstract: BACKGROUND: Treatment of early-stage Hodgkin's disease is usually tailored in line with prognostic factors that allow for reductions in the amount of chemotherapy and extent of radiotherapy required for a possible cure. METHODS: From 1993 to 1999, we identified 1538 patients (age, 15 to 70 years) who had untreated stage I or II supradiaphragmatic Hodgkin's disease with favorable prognostic features (the H8-F trial) or unfavorable features (the H8-U trial). In the H8-F trial, we compared three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) combined with doxorubicin, bleomycin, and vinblastine (ABV) plus involved-field radiotherapy with subtotal nodal radiotherapy alone (reference group). In the H8-U trial, we compared three regimens: six cycles of MOPP-ABV plus involved-field radiotherapy (reference group), four cycles of MOPP-ABV plus involved-field radiotherapy, and four cycles of MOPP-ABV plus subtotal nodal radiotherapy. RESULTS: The median follow-up was 92 months. In the H8-F trial, the estimated 5-year event-free survival rate was significantly higher after three cycles of MOPP-ABV plus involved-field radiotherapy than after subtotal nodal radiotherapy alone (98% vs. 74%, P<0.001). The 10-year overall survival estimates were 97% and 92%, respectively (P=0.001). In the H8-U trial, the estimated 5-year event-free survival rates were similar in the three treatment groups: 84% after six cycles of MOPP-ABV plus involved-field radiotherapy, 88% after four cycles of MOPP-ABV plus involved-field radiotherapy, and 87% after four cycles of MOPP-ABV plus subtotal nodal radiotherapy. The 10-year overall survival estimates were 88%, 85%, and 84%, respectively. CONCLUSIONS: Chemotherapy plus involved-field radiotherapy should be the standard treatment for Hodgkin's disease with favorable prognostic features. In patients with unfavorable features, four courses of chemotherapy plus involved-field radiotherapy should be the standard treatment. (ClinicalTrials.gov number, NCT00379041 [ClinicalTrials.gov].).

389 citations

Journal ArticleDOI
TL;DR: It is concluded that complement plays a pivotal role in the pathogenesis of side‐effects of rituximab treatment, as complement activation can not be prevented by corticosteroids.
Abstract: Treatment with rituximab, a chimaeric anti-CD20 monoclonal antibody, can be associated with moderate to severe first-dose side-effects, notably in patients with high numbers of circulating tumour cells. The aim of this study was to elucidate the mechanism of these side-effects. At multiple early time points during the first infusion of rituximab, complement activation products (C3b/c and C4b/c) and cytokines [tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and IL-8] were measured in five relapsed low-grade non-Hodgkin's lymphoma (NHL) patients. Infusion of rituximab induced rapid complement activation, preceding the release of TNF-α, IL-6 and IL-8. Although the study group was small, the level of complement activation appeared to be correlated both with the number of circulating B cells prior to the infusion (r = 0·85; P = 0·07) and with the severity of the side-effects. We conclude that complement plays a pivotal role in the pathogenesis of side-effects of rituximab treatment. As complement activation can not be prevented by corticosteroids, it might be relevant to study the possible role of complement inhibitors during the first administration of rituximab.

317 citations

Journal ArticleDOI
15 Sep 2002-Blood
TL;DR: After rituximab treatment, the humoral immune response to the recall antigens was significantly decreased when compared with the response before treatment, relevant regarding the feasibility of ritUXimab in maintenance treatment and may also offer a rationale for the treatment of antibody-mediated autoimmune diseases with ritukimab.

260 citations

Journal ArticleDOI
TL;DR: Until the benefit of this therapy is substantiated by large-scale phase III trials, high-dose chemotherapy should not be used in the adjuvant treatment of breast cancer, apart from in randomised studies.

244 citations

Journal ArticleDOI
TL;DR: The identification of FL as an immunologically functional disease in which an interaction of the tumor cells and the functional composition of the microenvironment determines the clinical behavior is supported.
Abstract: Purpose Despite the generally favorable clinical course in follicular lymphoma (FL), a minority of patients have a poor prognosis - with death within 3 years of diagnosis - most often due to transformation to aggressive disease. Patients and Methods In this study, we analyzed the potential of predicting early transformation on the basis of gene expression and immunologic parameters in FL biopsy samples taken at diagnosis. Results At the gene-expression level, FL is a highly uniform disease at the time of diagnosis, precluding the detection of sufficiently validated prognostic gene-expression profiles suitable for a clinical setting. Combinations of differentially expressed genes indicate that immunologic mechanisms play a differential role in the risk of early transformation. Using immunohistochemistry for specific cell populations, the spatial distribution to neoplastic follicles and the activation of CD4-positive T-helper cells (P = .002) and specifically T-helper 1 (P = .004) were shown to be highly discriminatory to predict early transformation. A role for functional modulation of follicular dendritic cells could also be supported (P = .04). Other cell populations, including CD68-positive macrophages and regulatory T cells, were not differentially present. Conclusion These results support the identification of FL as an immunologically functional disease in which an interaction of the tumor cells and the functional composition of the microenvironment determines the clinical behavior.

241 citations


Cited by
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01 Jan 2014
TL;DR: Lymphedema is a common complication after treatment for breast cancer and factors associated with increased risk of lymphedEMA include extent of axillary surgery, axillary radiation, infection, and patient obesity.

1,988 citations

Journal ArticleDOI
TL;DR: High-dose therapy with autologous stem-cell rescue is an effective first-line treatment for patients with multiple myeloma who are younger than 65 years of age and trend toward a greater survival benefit in the group of patients with a poor prognosis.
Abstract: background High-dose therapy with supporting autologous stem-cell transplantation remains a controversial treatment for cancer. In multiple myeloma, first-line regimens incorporating high-dose therapy yield higher remission rates than do conventional-dose treatments, but evidence that this translates into improved survival is limited. methods In this multicenter study, the Medical Research Council Myeloma VII Trial, we randomly assigned 407 patients with previously untreated multiple myeloma who were younger than 65 years of age to receive either standard conventional-dose combination chemotherapy or high-dose therapy and an autologous stem-cell transplant. results Among the 401 patients who could be evaluated, the rates of complete response were higher in the intensive-therapy group than in the standard-therapy group (44 percent vs. 8 percent, P<0.001). The rates of partial response were similar (42 percent and 40 percent, respectively; P=0.72), and the rates of minimal response were lower in the intensive-therapy group than in the standard-therapy group (3 percent vs. 18 percent, P<0.001). Intention-to-treat analysis showed a higher rate of overall survival (P=0.04 by the log-rank test) and progression-free survival (P<0.001) in the intensive-therapy group than in the standard-therapy group. As compared with standard therapy, intensive treatment increased median survival by almost 1 year (54.1 months [95 percent confidence interval, 44.9 to 65.2] vs. 42.3 months [95 percent confidence interval, 33.1 to 51.6]). There was a trend toward a greater survival benefit in the group of patients with a poor prognosis, as defined by a high beta 2 -microglobulin level (more than 8 mg per liter). conclusions High-dose therapy with autologous stem-cell rescue is an effective first-line treatment for patients with multiple myeloma who are younger than 65 years of age.

1,650 citations

Journal ArticleDOI
TL;DR: This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.
Abstract: Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

1,545 citations

Journal ArticleDOI
TL;DR: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.
Abstract: Purpose: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival Patients and Methods: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m2, with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m2, for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m2 Tamoxifen was given to 94% of patients with hormone receptor–positive tumors Results: There was no evidence of a doxorubicin dose effect At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m2, respectively The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald χ2 P = 0023; unadjusted Wilcoxon P = 0011) and 18% for death (adjusted P

1,252 citations

Journal ArticleDOI
TL;DR: This work states that antibodies exhibit various immunomodulatory properties and, by directly activating or inhibiting molecules of the immune system, antibodies can promote the induction of antitumour immune responses and form the basis for new cancer treatment strategies.
Abstract: Antibodies are important therapeutic agents for cancer. Recently, it has become clear that antibodies possess several clinically relevant mechanisms of action. Many clinically useful antibodies can manipulate tumour-related signalling. In addition, antibodies exhibit various immunomodulatory properties and, by directly activating or inhibiting molecules of the immune system, antibodies can promote the induction of antitumour immune responses. These immunomodulatory properties can form the basis for new cancer treatment strategies.

1,175 citations