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J J Battermann

Publications and source records attributed to J J Battermann.

At least 37 records · Page 2Linked to original sources
PubMed1999

Local low-dose IL-2 therapy.

Interleukin-2 (IL-2) is a powerful drug for treating cancer. However, it is only powerful if it is properly applied. That is, IL-2 should be applied at the tumor site, because at the transition of normal and malignant tissue are the tumor infiltrating cells. These should be activated by IL-2. Local application implies that IL-2 can be used in relatively low doses. It is becoming clear that even a single injection of IL-2 can cure cancer. IL-2 can also enhance the therapeutic effects of irradiation and Cisplatin. Locally applied IL-2 therapy is virtually non-toxic.

Animals↗
PubMed1998

[Iodine-125 implantation in localized prostate cancer; technique and results from 100 patients at the Academic Hospital, Utrecht].

OBJECTIVE: To evaluate the preliminary results of perineal implantation of I-125 seeds in patients with cancer of the prostate. DESIGN: Prospective descriptive cohort study. SETTING: Utrecht University Hospital, the Netherlands. METHODS: In the period from October 1989 to December 1996, a total of 149 patients with localized carcinoma of the prostate were treated with perineal implantation of I-125 seeds. One hundred of them could be evaluated. Results regarding progression and complications were collected prospectively. RESULTS: The median follow-up was 3 years (range 12-74 months). Progression of the disease was observed in 28 patients: local in eight, distant in four and both local and distant in one; 15 patients only showed a rise of prostate specific antigen level, without further symptoms. Fourteen patients were given supplementary treatment. No major complications were seen; four patients had persistent micturition problems and three, intestinal problems. CONCLUSION: Perineal I-125 implantation causes few complications and may constitute an alternative to external irradiation as well as to radical prostatectomy in the treatment of localized carcinoma of the prostate.

Brachytherapy↗
PubMed1998

Interrelationships of DNA-ploidy and cell proliferation markers with T-stage and N-stage in primary laryngeal tumors.

PURPOSE: The purpose of this study was to evaluate the interrelationships of DNA-ploidy and cell proliferation markers with T-stage and N-stage in primary laryngeal tumors. METHODS AND MATERIALS: DNA-index, S-phase fraction (SPF), 5-bromo-2'-deoxy-uridine (BrdUrd)-labeling index (LI), duration of S-phase (Ts), and potential doubling time (Tpot) were determined by flow cytometry. T-stage and N-stage were assessed in accordance with the TNM classification system (UICC 1987). RESULTS: T1-2-, when compared with T3-4-stage tumors, had significantly higher LI values (independent from N-stage) resulting in lower Tpot values. No such relationship was found with respect to N-stage. N1-3 tumors, as opposed to NO tumors, appeared to be characterized by a significantly shorter Ts (and, hence, a shorter Tpot). Ts values appeared to vary considerably (range 1.9-6.2 h). For DNA-aneuploidy, as opposed to DNA-diploidy, a significantly higher geometric mean LI was noted. Locally advanced (T3-4) tumors, when compared with T1-2 tumors, were characterized by a significantly higher percentage of DNA-aneuploidy. CONCLUSIONS: The reported lack of prognostic relevance of cell proliferation markers to predict radiation treatment efficacy may relate to a decreased proliferative capacity (LI, Tpot) in locally advanced (T3-4) tumors, as found in our series. In laryngeal tumors, the predictive value of cell proliferation markers (LI, Tpot) should, therefore, be evaluated after stratification for T-stage. The existence of higher LI values in DNA-aneuploidy tumors was confirmed in our series, stressing the need for distinction of DNA-diploid tumor cells from DNA-diploid normal cells. The prognostic potential of DNA-index was confirmed.

Cell Division↗
PubMed1998

Prognostic significance of cell proliferation markers and DNA-ploidy in head and neck tumors.

PURPOSE: The purpose of this study was to evaluate the prognostic significance of cell proliferation markers and DNA ploidy in patients with a squamous cell carcinoma of the head and neck region. METHODS AND MATERIALS: With flow cytometry, DNA index, G1PF-phase fraction (G1PF), S-phase fraction (SPF), 5-bromo-2'-deoxy-uridine (BrdUrd) labeling-index (LI), and potential doubling time (Tpot), were determined. T-stage and N-stage were assessed in accordance with the TNM classification system (UICC 1987). RESULTS: After multivariate analysis, it appeared that the probability of locoregional recurrent disease was increased by (a) T4-stage, (b) high values of the ratio SPF to LI, (c) DNA tetraploidy. Prognostic significance G1PF for SPF, LI, and Tpot was not demonstrated. However, the treatment regimen was not uniform for the total group of 103 patients. In 45 patients treated with radiation as single treatment and in 49 patients treated with postoperative radiotherapy, prognostic significance for G1PF, SPF, LI, and Tpot could not be demonstrated either. Separate statistical analysis was not executed for nine patients, treated by surgery alone. CONCLUSIONS: Prognostic significance could not be demonstrated for Tpot, LI, SPF, and G1PF in our series. The ratio of SPF to LI was found to be a promising prognosticator and is regarded to be indicative for the size of the hypoxic fraction. Prognostic significance for DNA ploidy was confirmed.

Analysis of Variance↗
PubMed1998

Prognostic relevance of cell proliferation markers and DNA-ploidy in gliomas.

The prognostic significance of clinically, histologically and flow cytometrically derived parameters was assessed in 49 glioma patients. With flow cytometry, DNA-index, S-phase fraction (SPF), 5-bromo-2'-deoxyuridine (BrdUrd)-labelling index (LI), and potential doubling time (Tpot) were determined. After univariate analysis of clinical variables such as, age, seizures as initial symptom, and duration of first symptom were found to be significantly associated both with proliferation rate and with local progression free survival (LPFS). Cytomorphological features such as, the presence or absence of mitosis, necrosis, and endothelial proliferation, were separately analysed and appeared to be significantly associated with LPFS. With respect to the cell proliferation markers, we observed a longer LPFS to be associated with a low SPF, a low LI, and a short Tpot. We did not observe a significant association between DNA-ploidy and LPFS. After multivariate analysis both of high and of low grade tumours, we found that neither LI, SPF, nor age had additional prognostic significance for cells in mitoses. We also demonstrated, that necrosis and endothelial proliferation had no additional prognostic significance to that for cells in mitoses. In the subgroup of low grade gliomas, in contrast to high grade gliomas, we noted prognostic significance for LI. We concluded, that i) the presence or absence of cells in mitoses was the strongest single prognosticator in gliomas, ii) in low grade gliomas LI holds prognostic significance.

Brain Neoplasms↗
PubMed1998

Treatment planning of brain implants using vascular information and a new template technique.

A new template technique has been developed for implanting hyperthermia catheters in the treatment of brain tumors. The technique utilizes an imaging template and a drill template which can be rigidly secured to the head with three skull screws. The anatomic and vascular information needed for hyperthermia treatment planning may be assessed with three-dimensional magnetic resonance (MR) imaging and angiography acquisitions which use a surface coil. In the companioning treatment planning system the catheter positions and lengths and the electrodes in the catheter can be interactively manipulated relative to the anatomy and vasculature. The visualization of the blood vessels relative to the template allows the minimization of the risk on intracranial hemorrhages. This template technique is useful for any brain tumor implants, especially when a large number of catheters are involved. A phantom test has shown that this procedure has an accuracy in the order of 1 mm provided that the MR-related geometry distortions are minimized.

Brain Neoplasms↗
PubMed1997

Local low-dose interleukin-2 induces systemic immunity when combined with radiotherapy of cancer. A pre-clinical study.

Tumor recurrence and outgrowth of metastases limit the therapeutical effect of radiotherapy. We have tested whether these problems can be overcome by supplementing radiotherapy with locoregional interleukin-2 (IL-2) treatment. The SL2 lymphoma and the M8013 mammary carcinoma were used. Mice bearing a 10-day-old s.c. tumor were locally irradiated and were treated daily with IL-2 peritumorally for 5 or 10 days. Low-dose IL-2 therapy improved local response (LR) and increased disease-free survival (DFS) in both tumor models following either single-dose irradiation or fractionated irradiation. For example, 93% of SL2-bearing mice treated with single-dose irradiation and 10 days of IL-2 experienced long-term DFS, compared with 17% for irradiation alone (p < 0.0001). Additionally, treatment of one tumor with irradiation +IL-2 led to anti-tumor effects in a second, untreated tumor in 80% of SL2-bearing mice. LR was increased to 100% and DFS to 70% when the second, non-irradiated tumor was also treated with peritumoral IL-2. We conclude that supplementing local radiotherapy with low doses of IL-2 results in increased local tumor control and regression of distant, non-irradiated tumors. This type of radioimmunotherapy is a promising new approach for the clinic.

Animals↗
PubMed1997

Evaluation of permanent I-125 prostate implants using radiography and magnetic resonance imaging.

PURPOSE: The aim of this study is the evaluation of permanent I-125 prostate implants using radiography and magnetic resonance imaging (MRI). METHODS AND MATERIALS: Twenty-one patients underwent radiography on the simulator and MRI within 3 days after implantation of the I-125 seeds. Isocentric radiographs were used for reconstruction of the seed distribution, after which registration with the seed-induced signal voids on MRI provided the seed positions in relation to the prostate. The prostate was contoured on the transversal magnetic resonance images, and dose-volume histograms were computed to evaluate the implants. The validity of the ellipsoidal prostate volume approximation, as applied in preimplant dose calculation, was assessed by comparison of ellipsoidal volumes given by prostate width, height, and length and prostate volumes obtained by a slice-by-slice contouring method, both on postimplant MRI. Prostate volume changes due to postimplant prostate swelling were assessed from radiographs taken at 3 days and 1 month after the implantation. RESULTS: The seeds were readily identified on T1-weighted spin-echo images and matched with the seed distribution reconstructed from the isocentric radiographs. The matching error, averaged over 21 patients, amounted to 1.8 +/- 0.4 mm (mean +/- standard deviation). The fractions of the prostate volumes receiving the prescribed matched peripheral dose (MPD) ranged from 32 to 71% (mean +/- standard deviation: 60 +/- 10%). Prostate volumes, obtained by the contouring method on postimplant MRI, were a factor 1.5 +/- 0.3 larger than the ellipsoidal volumes given by the prostate dimensions on postimplant MRI. Prostate volumes 3 days after the implantation were a factor 1.3 +/- 0.2 larger than the prostate volumes 1 month after the implantation. Registration of the reconstructed seed distribution and the MR images showed inaccuracies in seed placement, for example, two or more seeds clustering together or seeds outside the prostate. CONCLUSIONS: Registration of the reconstructed seed distribution and the MR images enabled evaluation of target coverage, which amounted to 60 +/- 10%. The discrepancy between prescribed dose and realized dose was caused by underestimation of the preimplant prostate volume due to the ellipsoidal approximation, postimplant prostate swelling at the time of evaluation, and inaccuracies in seed placement.

Brachytherapy↗
PubMed1997

Anti-tumor effects of local irradiation in combination with peritumoral administration of low doses of recombinant interleukin-2 (rIL-2).

The aim of this work was to improve radiotherapy results by immune stimulation. We tested the effects of a combination of radio- and immunotherapy, i.e., local low dose recombinant interleukin-2 (rIL-2) treatment, in two murine tumor models. Syngeneic tumors (SL2 lymphoma or M8013 mammary carcinoma) were induced subcutaneously on one or both flanks of mice. Irradiation was given either as a single dose (20 Gy) or fractionated (25 Gy) in 2 weeks. One or two cycles of rIL-2 were given concurrent with or subsequent to radiotherapy. One cycle of rIL-2 consisted of peritumoral injections administered on 5 consecutive days. Treatment effects were measured in terms of local tumor response and disease-free survival (DFS). The combined treatment modality was significantly better than treatment with either irradiation alone or rIL-2 alone. When tumors were inoculated on both flanks of the mice, combined radioimmunotherapy of one of the tumors also resulted in regression of the contralateral untreated tumor, indicating that a systemic anti-tumor immune reaction was induced. Additional rIL-2 injections did not enhance radiation toxicity. In conclusion supplementing irradiation with locally administered low doses of rIL-2 results in better local anti-tumor responses and DFS rates than either treatment alone without enhanced treatment toxicity. Furthermore, the local treatment induces a systemic anti-tumor reaction, influencing the growth patterns of a second, untreated tumor.

Animals↗
PubMed1997

S-phase fraction, 5-bromo-2'-deoxy-uridine labelling index, duration of S-phase, potential doubling time, and DNA index in benign and malignant brain tumors.

Seventy-one histologically malignant brain tumors, 52 histologically benign brain tumors, and 14 cerebral metastases were characterized according to DNA content and proliferative capacity. DNA ploidy, DNA index (DI), S-phase fraction (SPF), 5-bromo-2'-deoxy-uridine (BrdUrd) labelling index (LI), duration of S-phase (Ts), and potential doubling time (Tpot) were assessed by flow cytometry (FCM). In histologically benign tumors, a high percentage of DNA diploid tumors and a low proliferative capacity in DNA diploid tumors were found. Histologically malignant tumors and cerebral metastases were both found to be characterized by a low percentage of DNA diploid tumors and a high proliferative capacity in DNA diploid tumors. The proliferative capacity of DNA aneuploid benign tumors and that of DNA aneuploid malignant tumors, however, appeared not to differ significantly. The number of DNA aneuploid tumors was small. Duration of S-phase was short (range 3.9-4.7 hr) and appeared not to differ between the three groups. From this, the observed differences in Tpot values should be accredited mainly to differences in LI. High-grade as well as low-grade gliomas both appeared to be characterized by malignant (FCM) features, i.e., 1) a high percentage DNA aneuploidy, 2) a high mean DI (for DI > 1), and 3) a high proliferative capacity.

Aneuploidy↗
PubMed1996

Dose uniformity in MECS interstitial hyperthermia: the impact of longitudinal control in model anatomies.

The quality of temperature distributions that can be generated with the multi-electrode current source (MECS) interstitial hyperthermia system, which allows 3D control of the spatial SAR distribution, has been investigated. For the investigations, computer models of idealized anatomies were used. These anatomical models did not contain discrete vessels. Binary-media anatomies, containing media interfaces oriented parallel, perpendicular or oblique with respect to the long axis of the implant, represent simple anatomies which can be encountered in the clinic. The implant volume was about 40 cm3. A seven-catheter hexagonal implant geometry with a nearest-neighbor distance of 15 mm was used. In each interstitial probe between one and four electrodes with a diameter of 2.1 mm were placed along an "active section' with a length of 50 mm. The electrode segments had lengths of 50, 20, 12 and 9 mm. This study shows that even with high contrasts in electrical and thermal conductivity in the implant it remains possible to obtain satisfactory temperature distributions with the MECS system. Due to its 3D spatial control the temperature homogeneity in the implant can be made quite satisfactory, with T10-T90 of the order of 2-3 K. Treatment planning must ensure that the placement of the current source electrodes is compatible with the media configuration.

Biophysical Phenomena↗
PubMed1994

The influence of respiration induced motion of the kidneys on the accuracy of radiotherapy treatment planning, a magnetic resonance imaging study.

An MRI study has been performed to determine the respiration induced motion of the kidneys. Under normal respiration conditions displacements of the left and right kidney varied from 2 to 24 mm and 4 to 35 mm, respectively. Under forced respiration conditions displacements were larger and ranged from 10 to 66 mm for the left kidney and 10 to 86 mm for the right kidney. The influence of kidney motion on the radiation dose was determined for patients irradiated on the total abdomen for ovarian cancer with shielding of the kidneys during part of the treatment. The kidney motion resulted in a larger fraction of the kidney volume receiving a dose between 20 and 22 Gy.

Adult↗
PubMed1992

Body measurements, estrogen availability and the risk of human breast cancer: a case-control study.

Recent studies on lifestyle-related mechanisms involved in cardiovascular risk offer important clues for a better understanding of breast-cancer epidemiology. Central body-fat distribution promoted by an affluent dietary intake and a sedentary lifestyle over many years is related to elevated serum triglycerides and free fatty acids, with lower levels of sex-hormone-binding globulin (SHBG). The resulting greater availability of estradiol not bound to SHBG could help to explain the high breast-cancer incidence in Western industrialized countries. We conducted a case-control study comparing 225 women aged 38 to 75 years with operable (stage I or II) breast cancer and 441 women of the same age having no breast cancer who participated in a population-based breast-cancer screening program. Body fatness, as measured by body mass index (BMI), fat distribution as measured by waist-to-hip girth ratio (WHR), body height, serum lipids, SHBG and the available fraction of estradiol were analyzed in a conditional logistic regression, together with family history for breast cancer, reproductive history and smoking. Post-menopausal cases showed no difference in body fatness (BMI), but a significant preponderance of central adiposity (WHR). In contrast, pre-menopausal cases were significantly leaner, but had a similar body-fat distribution as compared with controls. In all women, WHR, and less strongly BMI, was positively correlated with serum levels of triglycerides and available estradiol fractions. An independent, positive linear correlation between body height and relative risk (RR) was observed. Moreover, a significant correlation between SHBG and menarcheal age was seen in cases, but not in controls. These data support our hypothesis that lifestyle relates to breast-cancer risk by metabolic-endocrine mechanisms which modulate the availability of individual sex-steroid concentrations in plasma. The findings of height as a risk factor and adult SHBG levels being correlated with menarcheal age suggest that lifestyle factors promoting breast-cancer development already act around puberty. The leanness of pre-menopausal cases awaits further explanation.

Adult↗