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D De Ruysscher

Publications and source records attributed to D De Ruysscher.

16 recordsLinked to original sources
PubMed2005

Systematic review and meta-analysis of randomised, controlled trials of the timing of chest radiotherapy in patients with limited-stage, small-cell lung cancer.

BACKGROUND: We undertook a systematic review and literature-based meta-analysis to determine whether the timing of chest radiotherapy may influence the survival of patients with limited-stage small-cell lung cancer (LS-SCLC). MATERIALS: Eligible randomised controlled clinical trials were identified according to the Cochrane Collaboration Guidelines, comparing different timing of chest radiotherapy in patients with LS-SCLC. Early chest irradiation was defined as beginning within 30 days after the start of chemotherapy. RESULTS: Considering all seven eligible trials, the overall survival at 2 or 5 years was not significantly different between early or late chest radiotherapy. When only trials were considered that used platinum chemotherapy concurrent with chest radiotherapy, a significantly higher 5-year survival was observed when chest radiotherapy was started within 30 days after the start of chemotherapy (2-year survival: OR: 0.73, 95% CI 0.51-1.03, P = 0.07; 5-year survival: OR: 0.64, 95% CI 0.44-0.92, P = 0.02). This was even more pronounced when the overall treatment time of chest radiotherapy was less than 30 days. CONCLUSIONS: There are indications that the 5-year survival rates of patients with LS-SCLC are in favour of early chest radiotherapy, with a significant difference if the overall treatment time of chest radiation is less than 30 days.

Carcinoma, Small Cell↗
PubMed2005

Early versus late chest radiotherapy for limited stage small cell lung cancer.

BACKGROUND: It is standard clinical practice to combine chemotherapy and chest radiotherapy in treating patients with limited-stage small cell lung cancer. However, the best way to integrate both modalities is unclear. OBJECTIVES: To establish the most effective way of combining chest radiotherapy with chemotherapy for patients with limited-stage small cell lung cancer in order to improve long-term survival. SEARCH STRATEGY: The electronic databases MEDLINE, EMBASE, Cancerlit and the Cochrane Central Register of Controlled Trials (CENTRAL), reference lists, handsearching of journals and conference proceedings, and discussion with experts were used to identify potentially eligible trials, published and unpublished. SELECTION CRITERIA: Randomised controlled clinical trials comparing different timing of chest radiotherapy in patients with limited-stage small cell lung cancer. DATA COLLECTION AND ANALYSIS: Seven randomised trials were reviewed. There were differences in the timing and the overall treatment time of chest radiotherapy, the overall treatment time of , and the type of chemotherapy used. MAIN RESULTS: No significant differences in the 2-year and the 5-year survival were found, whether chest radiotherapy was delivered within 30 days after the start of chemotherapy or later. When the only study that delivered chest radiotherapy during cycles of non-platinum chemotherapy was excluded, a trend for the 5-year survival was observed (RR:0.93, p=0.07) in favour of early radiation, but not for the 2-year survival. Survival at 5 years, but not at 2 years, was significantly better for those having early chest radiotherapy delivered in an overall treatment time of less than 30 days compared with a longer treatment time (RR: 0.90, p=0.006). These results, however, should be interpreted with caution because the largest trial has follow-up data at three years, but not later. It remains to be seen what the effect of longer follow up will be for 5-year survival rates. Local tumour control was not significantly different between early and late chest radiotherapy. The incidence of severe pneumonitis or severe oesophagitis was not significantly different for early versus late thoracic radiotherapy. However, a trend for a higher chance to develop pneumonitis when early chest radiotherapy was delivered during non-platinum based chemotherapy was observed. AUTHORS' CONCLUSIONS: At present, it is uncertain whether the timing of chest radiotherapy as such is important for survival. The optimal integration of chemotherapy and chest radiotherapy in patients with limited-stage small cell lung cancer is unknown. Therefore, further research is needed to establish the most effective combination of radiotherapy and chemotherapy in this disease.

Carcinoma, Small Cell↗
PubMed2001

Heterotaxy syndrome in an adult, with polysplenia, visceral and cardiovascular malposition.

A rare case of an asymptomatic heterotaxy syndrome associated with dextrocardia is presented in a 45-year-old woman. This anomaly was incidentally discovered on computed tomography and ultrasound of the upper abdomen. Besides the presence of multiple abnormally positioned spleens, right-sided stomach, left-sided liver, short pancreas and venous anomalies, like interrupted left-sided inferior vena cava with azygos continuation, and dextrocardia were seen. Although cardiac abnormalities are frequently associated with heterotaxy syndromes with polysplenia in children, this is far less frequent in adults because of early decease in children with cardiac abnormalities. To the best of our knowledge, this is the third reported case of heterotaxy with polysplenia associated with dextrocardia in an asymptomatic adult patient.

Female↗
PubMed2000

Chest radiotherapy in limited-stage small cell lung cancer: facts, questions, prospects.

OBJECTIVE AND STUDY DESIGN: Limited-disease small cell lung cancer (LD-SCLC) is initially very sensitive to both radiotherapy and chemotherapy. However, the 5-year survival is generally only 10-15%, with most patients failing with therapy refractory relapses, both locally and in distant sites. The addition of chest irradiation to chemotherapy increases the absolute survival by approximately 5%. We reviewed the many controversies regarding optimal timing and irradiation technique. RESULTS: No strong data support total radiation doses over 50 Gy. According to one phase III trial and several retrospective studies, increasing the volume of the radiation fields to the pre-chemotherapy tumour volume instead of the post-chemotherapy volume does not improve local control. CONCLUSIONS: The total time in which the entire combined-modality treatment is delivered may be important. From seven randomized trials, it can be concluded that the timing of the radiotherapy as such is not very important. Some phase III trials support the use of accelerated chest radiation together with cisplatin-etoposide chemotherapy, delivered from the first day of treatment, although no firm conclusions can be drawn from the available data. The best results are reported in studies in which the time from the start of treatment to the end of the radiotherapy was less than 30 days. This has to be taken into consideration when treatment modalities incorporating new chemotherapeutic agents and radiotherapy are considered.

Antineoplastic Agents↗
PubMed1998

Sequential treatment with vindesine-ifosfamide-platinum (VIP) chemotherapy followed by platinum sensitized radiotherapy in stage IIIB non-small cell lung cancer: a phase II trial.

PURPOSE: Daily administration of cisplatin concomitant with radiotherapy improved the overall survival in inoperable non-small cell lung cancer (NSCLC) in one EORTC study. In this study, we prospectively investigated the efficacy and toxicity of a sequential treatment with three cycles of vindesine-ifosfamide-platinum (VIP) induction chemotherapy, followed by daily cisplatin-sensitized radiotherapy. METHODS: Between June 1993 and June 1995, 23 previously untreated patients with stage IIIB NSCLC with World Health Organization performance status 0 or 1 were included. Chemotherapy consisted of platinum 30 mg/m2 and ifosfamide 1200 mg/m2 i.v. on days 1, 2 and 3, and vindesine 3 mg/m2 i.v. on days 1 and 8, every 4 weeks. After three cycles and at least stable disease, radiotherapy was started (30 Gy in 10 fractions, followed by a boost of 22 Gy in 10 fractions). Each fraction was preceded by Platinum 6 mg/m2 i.v. RESULTS: Nineteen patients completed the sequential therapy. One patient died from neutropenic sepsis during the first cycle of chemotherapy, and three patients had progressive disease after chemotherapy. The overall response rate after sequential therapy was 47% (95% confidence interval 24-80), median survival was 10.6 months, 1- and 2-year survival rates were 47 and 16%, respectively. Major toxicity consisted of neurotoxicity grade III-IV in 18% and of leukopenia grade III-IV in 22% of the patients. Acute radiation pneumonitis grade III occurred in 11% of the patients. CONCLUSION: Three-drug VIP induction chemotherapy followed by cisplatin-sensitized radiotherapy is feasible, with acceptable, albeit substantial, toxicity. In spite of the theoretically promising sequence of therapies, survival results remain disappointingly low.

Aged↗
PubMed1996

The treatment of osseous metastases of hormone-refractory prostate cancer with external beam radiotherapy and Strontium-89.

Metastatic bone disease from hormone-refractory prostate cancer can lead to significant morbidity such as pain, nerve compression and fractures which diminishes the quality of life of these patients substantially. Pain from osteoblastic metastases can significantly be improved by both external radiotherapy and Strontium-89 (89Sr), whereas lytic metastases are only responsive to external irradiation. Pain relief is obtained in approximately 80% of patients. Toxicity is mild and retreatment is usually possible. External beam radiotherapy is indicated when spinal cord or nerve root compression is demonstrated, or when osteolytic metastases with danger of fracture are visualized. External radiotherapy and Strontium-89 are important treatments to palliate patients suffering from metastatic prostate cancer. Because of their mild toxicity and highly effective analgesic effect, implementation of irradiation and 89Sr should be start of early in the disease process of these patients in order to keep them ambulatory and pain-free as long as possible.

Bone Neoplasms↗
PubMed1992

The influence of neonatal thymectomy on the development of radiation myelopathy in rats.

To investigate the possible contribution of cellular immunity in the development of radiation injury of the central nervous system, Wag/Rij rats were thymectomized at birth and irradiated to the cervical spinal cord at the age of 3 months. At the time of paralysis or at the end of the follow-up period (when rats were 1-year-old) the animals were sacrificed and the mediastinum was examined histologically. In 95% of the neonatally thymectomized animals no thymus was left. These rats showed a firm impairment of the cellular immunity, as they had a 40% reduction of the T-lymphocytes in the spleen, and a 70% reduction of the mixed lymphocyte reaction, compared to age-matched controls. Both single dose and two-fraction irradiation experiments were performed. No modification of the latency time to develop paralysis was observed comparing thymectomized and age-matched controls. The incidence of foreleg paralysis after cervical spine irradiation (single dose or two-fraction) was identically distributed in the follow-up period for both neonatally thymectomized and control Wag/Rij rats. The ED50 value derived in the single dose experiments was 20.3 Gy for the control animals, and 20.9 Gy for thymectomized rats, and in the two fraction experiments 29 Gy for controls and 29.6 Gy for thymectomized rats. None of these differences are significant. It appears that neonatal thymectomy, in spite of its firm suppression of the cellular immunity, has no major influence on the development of radiation myelopathy in rats.

Animals↗
PubMed1992

Changes of lymphocyte subsets after local irradiation for early stage breast cancer and seminoma testis: long-term increase of activated (HLA-DR+) T cells and decrease of "naive" (CD4-CD45R) T lymphocytes.

Blood lymphocyte subsets of early breast cancer patients and of men with stage I seminoma of the testis were studied up to 6 years after radiotherapy. Similar results were obtained in the two patient groups. After a temporary decrease, the CD4-w29 or "memory" T cells recovered completely, while the CD4-45R or "naive" T cells remained decreased up to 6 years after irradiation. The number of CD8 T lymphocytes did not change during or after treatment. Because of the decrease of a subset of CD4 cells, and the unchanged values of CD8 cells, the CD4/CD8 ratio decreased significantly after irradiation, and remained lower than before treatment up to 5-6 years after radiotherapy. The number of both HLA-DR positive CD4 and HLA-DR positive CD8 T cells ("activated" T cells) increased significantly after irradiation. The natural killer (NK) cells were not affected by treatment. We propose that the recovery of the CD4 cells is limited to the CD4-w29 ("memory") population because of thymic dysfunction in older humans. The impact of the observed immune modulation on the low susceptibility for infections after local irradiation, and on putative antitumour immune responses is discussed.

Adult↗
PubMed1991

A subset of asialo GM1+ cells play a protective role in the occurrence of graft-versus-host disease in mice.

In three different murine models of bone marrow (BM) transplantation the capacity of asialo GM1+ cells to suppress graft-vs-host disease (GVHD) was investigated. In a first model, total lymphoid irradiation (TLI)-treated BALB/C mice were given 1 mg of anti-asialo GM1 antibody. This led to the disappearance of functional suppressor cells after TLI. Injections of anti-asialo GM1 into TLI-treated BALB/C mice before infusion of 30 x 10(6) fully allogeneic (C3H) BM cells, led to a significantly decreased survival rate as compared to TLI-treated mice injected with control serum before BM transplantation (survival 29 and 83%, respectively, at 120 days after transplantation, p = 0.0032 log rank). The mortality of the former group was due to GVHD as 1 degree all dying animals showed clinical and histologic signs of GVHD, 2 degrees all animals were chimeric and 3 degrees mice receiving no or syngeneic BALB/C BM had excellent survival rates excluding BM aplasia or increased susceptibility for infections as reason for the mortality of the allogeneic BM recipients. In a second model, asialo GM1+ cells were removed in vitro from the C3H BM inoculum before injection into lethally irradiated (9 Gy) BALB/C recipients. In mice kept in specific pathogen-free conditions, this procedure resulted into a significant mortality (12/12) as compared to mice receiving BM pretreated with control serum (1/12, p = 0.0001 log rank). When kept in conventional housing, GVHD occurred in both groups but much earlier in the group receiving anti-asialo GM1-treated BM (median survival time 6 vs 46 days for the control mice, p = 0.001 log rank). No animal receiving anti-asialo GM1 and treated with syngeneic BM died, thus excluding toxicity, increased susceptibility to infections, or decreased graft take as a cause of mortality. In a last model, asialo GM1 cells were removed from syngeneic BM in a BM transplantation model in which T cell-depleted syngeneic (BALB/C) and non-T cell-depleted allogeneic (C3H) BM was administered to lethally irradiated (9 Gy) BALB/C mice. Also in this model GVHD-related mortality only occurred in the group of mice receiving syngeneic BM from which asialo GM+ cells were depleted before infusion (3/12). Our experiments thus clearly show that asialo GM1+ cells from both recipient (the TLI model) as well as donor origin (the TBI experiments) can suppress the occurrence of GVHD.

Animals↗
PubMed1990

Measurement of alloantibody by flow cytometry.

A new method based on flow cytometry has been developed to determine IgG alloantibodies in the serum of immunized rodents. The method utilizes target lymphoid cells, diluted serum and labeled anti-mouse or anti-rat IgG antibodies. In serum from highly immunized animals alloantibodies could be demonstrated up to a dilution of (3 x 10(4))-1 which makes the test approximately 300 times more sensitive than a simultaneously performed complement-dependent cytotoxicity assay (CDCA). Moreover a linear relationship between the amount of alloantibody and the log value of the mean fluorescence of the target cells was found. This linearity permits the comparison of alloantibody production between individual samples by comparing the mean fluorescence values. The reproducibility of the assay was excellent since the coefficients of variation for all dilutions were less than 15%. By using two-color fluorescence the method can discriminate alloantibodies directed against class I and class II MHC antigens. Finally, in addition to its high sensitivity and good reproducibility, the method was found to be at least twice as fast as CDCA.

Animals↗
PubMed1990

Mechanisms involved in the differential recovery of CD4 and CD8 T-lymphocytes after local irradiation in mice.

The mechanisms involved in the differential recovery of CD4 (helper/inducer phenotype) and CD8 (cytotoxic/suppressor phenotype) T-lymphocytes after fractionated local irradiation were investigated. In mice, a better recovery of CD4 cells than of CD8 cells was found, while the reverse has been described in humans. Differences in radiosensitivity between CD4 and CD8 mouse splenocytes could not be found. No sequestration of CD8 cells in irradiated tissues could be demonstrated. Irradiation of the thymus did not influence the observed immune changes. Altered thymic production of CD4 and CD8 cells could be excluded by intrathymic injection of FITC (fluorescein isothiocyanate). Hindlimb and tail irradiation did not induce changes in the morphology of the thymus and the phenotype of the thymocytes. These results suggest that the differential recovery of CD4 and CD8 T-lymphocytes after local irradiation is determined by extrathymic factors in man and mice, and that the observed differences in immune recovery between man and mice are due to defective thymic function in the former and normal function in the latter.

Animals↗
PubMed1989

Immunologic changes after loco-regional radiotherapy and fractionated total body irradiation (TBI) in mice.

The immunologic effects of fractionated irradiation to both hind limbs and the tail of adult (2.5-3 months old) male Balb/c mice were investigated. A dose of 34 Gy given in 17 fractions of 2 Gy, 1 fraction per day, 5 days per week, was delivered with a 60Co source. A significant decrease of the total splenocyte count (29% of control value) and of the PHA(phytohemagglutinin)-induced proliferation of T cells (22% of control value) was found immediately after irradiation. Both parameters normalized within 30 days after irradiation. Immediately after irradiation, the MLC (mixed lymphocyte culture) was supranormal (126% of control value), dropped to 45% 1 week later, and normalized within 1 month after radiotherapy. The NK (natural killer) activity was significantly decreased only the first week after loco-regional irradiation, while the LAK (lymphokine activated killer) activity was not altered at all. The percentage of goat-anti-mouse+ cells (mainly B lymphocytes) was not changed immediately after loco-regional irradiation, but rose to supranormal values (175% of control level) 3 months after irradiation. A persistent decrease of the percentage and the absolute numbers of the Lyt2+ cells (= CD8+ cells, suppressor/cytotoxic phenotype) was observed up to 3 months after irradiation, while the percentage of L3T4+ cells (= CD4+ cells, helper phenotype) remained normal for the total follow-up. No differences in allogeneic skin graft survival could be demonstrated between irradiated and control animals. The observed immunological effects could not be explained by the scatter irradiation to the whole body as total body irradiation (TBI) administered in a dose and dose rate similar to the scatter dose did not result in persistent immunologic changes. No dose-rate effect could be demonstrated in a low dose fractionated total body irradiation schedule. A total body irradiation similar to the scatter dose in humans did not result in significant immunologic changes.

Animals↗