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Biomedical subjects

H Sack

Publications and source records attributed to H Sack.

At least 19 recordsLinked to original sources
PubMed1992

Radiosensitivity, repair capacity, and stem cell fraction in human soft tissue tumors: an in vitro study using multicellular spheroids and the colony assay.

Radiation doses necessary to control 50% of spheroids (SCD50) were determined for five human soft tissue tumor lines after single dose and fractionated irradiation. Spheroids with 1000-1500 cells were used throughout. A similar number of cells per spheroid resulted in different sized spheroids for the respective cell lines. The parameters alpha, beta, and the number of regenerating cellular units per spheroid (SRU) were estimated from the spheroid control data using a direct fit according to the linear quadratic model assuming Poisson statistics. The number of spheroid regenerating cellular units was also determined from the growth delay at doses required for 10% spheroid control. In addition, alpha, beta, and the fraction of clonogenic cells of the five cell lines were obtained from a soft agar colony forming assay. The most precise parameter for radiation sensitivity was the SCD50, with a coefficient of variation smaller than 5%. SCD50 values ranged from 5.9 to 11.0 Gy for the five soft tissue tumor lines. Two of the five cell lines showed significantly higher alpha values and lower calculated survival fractions after 2 Gy (SF2) in the soft agar clonogenic assay than in the spheroid control assay. This points to a resistance-enhancing effect in the spheroid system. Whereas the fractions of SRU from the number of cells per spheroid, estimated from the spheroid control and growth delay assays, agreed well, no significant correlation existed between the fraction of SRU and the fraction of clonogenic cells in the soft agar colony forming assay. The alpha/beta ratios as a descriptive measure of the fractionation sensitivity of the tumor cell spheroids in the spheroid control assay corresponded well with those derived from the dose-cell survival data using a soft agar colony forming assay. Two of the five cell lines showed high fractionation sensitivities with alpha/beta values smaller than 5 Gy while those of the remaining three ranged from 7.8 to 10.8 Gy. Spheroids are structurally more similar to in vivo tumors than monolayer cultures. From the observed lack of correlation in the radiosensitivity parameters alpha and SF2 as well as in the fraction of SRU or clonogenic cells obtained from the spheroid control assay or the colony forming assay, one would expect even greater differences between results from colony forming assays and the radiosensitivity of in vivo tumors, at least for human soft tissue sarcomas.

Cell Aggregation↗
PubMed1992

Blood flow and steady state temperatures in deep-seated tumors and normal tissues.

Blood flow related data obtained in different deep-seated tumors and adjacent normal tissues were analyzed in 28 patients who were treated with combined regional hyperthermia and radiation for recurrent or metastatic tumors. The evaluation of blood flow related data has been made using the thermal clearance/thermal cooling coefficient technique and dynamic computed tomography. With both methods significant differences in global perfusion have been observed between tumor center and tumor periphery, between tumor and normal tissue (deep muscle and fat tissue), and between tumor entities. Washout rates or thermal cooling coefficient values, as well as the enhancement of contrast material over baseline (expressed in delta Hounsfield Units), correlated significantly with the achieved steady state temperatures for different tissue categories (i.e., tumor center, tumor periphery, different tumor entities, normal tissue). Thermal cooling coefficient values higher than 63000-83000 W/m3-K (washout rates higher than 15-20 ml/100 g-min) or values of enhancement of contrast material higher than delta 20-25 HU coincide with a limitation in achieving therapeutic temperatures higher than 40 degrees C.

Abdominal Neoplasms↗
PubMed1992

Radioresponsiveness, sublethal damage repair and stem cell rate in spheroids from three human tumor lines: comparison with xenograft data.

Dose-control curves after fractionated irradiation were generated for small oxic spheroids from the two human glioma cell lines, U87 and A7, as well as the squamous cell carcinoma line FaDu. These data were fitted by the linear quadratic model assuming Poisson statistics. The alpha/beta values of A7, U87, and FaDu spheroids, respectively were 10.3 (8.1-12.9) Gy, 17.8 (15.1-21.1) Gy, and 37.9 (29.1-51.5) Gy. These data were compared with those previously published by Suit et al. (31) and Zietman et al. (40) for 6 mm xenografts of U87 and FaDu after fractionated irradiation and for A7 after single dose irradiation under clamped conditions. A good agreement in the alpha/beta values was observed for U87 and Fadu xenografts and spheroids assuming an oxygen enhancement ratio (OER) of 2.7. In addition, the ranking according to the single doses needed to control 50% of the tumors agreed for xenografts and spheroids from the three cell lines. U87 was the most resistant line in both model systems, followed by A7 and FaDu. However, the absolute values of alpha and beta, obtained from the direct fit to the dose-control data were only about half as high for U87 and FaDu xenografts than for the spheroids. Monte Carlo simulations showed that this discrepancy can be explained by a greater tumor heterogeneity of the xenografts. While the number of critical stem cells or spheroid rescuing units equaled the number of cells per spheroid for the three cell lines, the percentage of tumor rescuing units for Fadu and U87 xenografts was estimated to be below 1%. In a next step, survival curves were generated for exponentially growing cells of the three lines. A7 cells were significantly more radioresistant when plated on tissue plastic than in soft agar. Using the most resistance-promoting colony assay conditions for each cell line, a good agreement was observed for the alpha and SF2Gy values calculated from the colony and spheroid control data. This study shows that the spheroid model can quantitatively predict the repair capacity of sublethal damage as well as the rank order of radiation sensitivity of in vivo tumors.

Animals↗
PubMed1992

[The special aspects in the planning and use of an electron linear accelerator facility for intraoperative radiotherapy (IORT)].

Limiting conditions for the planning of the installation of an electron linear accelerator in an operating theatre are described taking into account the radiotherapeutical and surgical requirements based on the example of the Essen facility for intraoperative radiotherapy (IORT) with electrons. Special features of the facility like a non-contact electron applicator system with television monitoring, table-top trolley, which is used also during irradiation, are explained in detail. Measured isodose curves for all tubes and all electron energies serve for the radiotherapist as criteria for decision on tube size and electron energy selection during surgical operation. The influence of misalignments of the tube on dose distributions is investigated. Limit values of alignment tolerances are deduced. Daily constancy tests for monitor calibration, electron energy, and tube alignment system are to be performed for quality assurance. Tables of the planned and realized treatments and of a representative time schedule of an IORT give a survey on the indications and the necessary time effort and staff. Completion of the set of tubes as well as optimization of the tube fixation accessory and of the table-top trolley are main subjects for future developments.

Anesthesiology↗
PubMed1991

Hyperthermia in eccentrically located pelvic tumors: excessive heating of the perineal fat and normal tissue temperatures.

Regional hyperthermia in deep-seated tumors can be limited by excessive heating of normal tissues, usually associated with pain or local discomfort. In this report, 57 hyperthermia treatments in 8 patients with locally advanced presacral recurrences of colorectal cancer were analyzed with respect to normal tissue temperatures, especially with respect to the perineal fat temperature. In 27 treatments, 1 to 2 catheters had been inserted from the perineal region through a large part of the perirectal and presacral fat into the tumor, so that temperature profiles of the perineal fat could be obtained. The mean maximum temperature (+/- SD) of the vagina, rectum, bladder, muscle tissue, and perineal fat was 40.8 +/- 1.2 degrees C, 40.9 +/- 1.6 degrees C, 40.5 +/- 1.6 degrees C, 39.8 +/- 0.7 degrees C, and 42.6 +/- 1.1 degrees C, respectively. The mean maximum systemic temperature (+/- SD) was 37.7 +/- 0.7 degrees C. In 42% of the treatments, the temperature in the perineal fat ranged between 43 and 46 degrees C and was treatment-limiting. In conclusion, overheating of the perineal fat is a problem in the treatment of eccentrically located tumors of the presacral region when relatively high temperatures in the tumor will be maintained for longer time periods.

Adipose Tissue↗
PubMed1991

[Postoperative radiotherapy of salivary gland tumors. Prognostic factors and treatment results].

A retrospective analysis of 63 patients with malignant major salivary gland tumours treated between 1972 and 1988 is presented. In 54 patients the tumour was located in the parotid gland, in the remaining nine patients the tumour was located in the submandibular gland, 31 patients were treated for stage I to II disease, 32 patients for stage III to IV disease. All patients were irradiated postoperatively using 60 Co. 137 Cs photons or electrons of adequate energies. As basic techniques ipsilateral portals, a wedge pair of portals or parallel opposed fields were used. The target doses ranged between 45 and 70 Gy with fractions of three to five times 2 to 3 Gy weekly, dependent on postoperative status and stage. In 25% of the patients a local recurrence was evident after radiotherapy with 13% developing distant metastases. The five-year survival was 95% for stage I, 83% for stage II, 30% for stage III and 7% for stage IV. Additionally, the prognosis varied according to lymph node involvement, grading and microscopic or macroscopic residual disease.

Adolescent↗
PubMed1991

Repair capacity and kinetics in spheroids from a lung metastasis of a human soft tissue sarcoma: a growth delay study.

Spheroids grown from the human cell line EF8 of a lung metastasis of a human malignant fibrous histiocytoma were given fractionated irradiation with 60Co gamma rays at passages 31 and 32. The mean diameter of the spheroids at the time of treatment was 250 microns. Growth delay was used as the end point in these studies. Two experiments were carried out to determine the capacity and kinetics of repair of sublethal damage. In the first experiment, one, two, and five fractions were given at three or four dose levels with fixed intervals of 360 min. In the second experiment, schedules with two and four dose fractions and intervals of 0, 20, 60, 120, and 360 min were used, each at two dose levels. Data analysis was performed by a direct method based on the alpha/beta model and first-order repair kinetics of radiation damage. In both experiments, the alpha/beta value of EF8 spheroids was estimated to be about 8 (6-10) Gy. The rate constant of repair, mu, and its 95% confidence interval were estimated to be 0.62 (0.40-0.84) 10(-2) min-1, equivalent to a half-time of repair (T1/2) of 112 (83-172) min. A more detailed analysis of the data of the second experiment revealed a significant dependence of the rate constant of repair, mu, on the total radiation effect induced by the fractionated radiation treatments with short overall times. With increasing level of effect, mu decreased. These data indicate that the half-time of recovery of a human tumor can be longer than that of the surrounding normal tissue, in this case lung, at least for a limited range of doses and for some fractionation schedules.

Cobalt Radioisotopes↗
PubMed1990

[Chemotherapy of nonendemic Burkitt's lymphoma].

14 patients (12 men, 2 women, mean age 26.3 [15-47] years) with histologically confirmed Burkitt's lymphoma were subjected between 1984 and 1989 to chemotherapy originally developed for treating lymphomas in children. Treatment consisted of medium doses of methotrexate, cyclophosphamide, teniposide, cytarabine, adriamycin and prednisone, intrathecal administration of methotrexate and if necessary prophylactic or therapeutic irradiation of the cranium. Most of the patients (64%) were in advanced stages of the disease. The rate of complete remissions was 100%. Four patients (29%) had a recurrence. Side effects were leukopenia (WHO grade III and IV) in 71%, grade III anaemia in 43% and grade III-IV thrombopenia in 29% of the patients. Considerable mucositides in 5 of the 14 patients (36%), and in one case a tumour lysis syndrome with transient renal insufficiency were other therapy-induced side effects. These results suggest that this treatment course can be successful also in non-endemic Burkitt's lymphoma in adolescents and adults.

Adolescent↗
PubMed1990

New and recurrent tumor foci following local treatment as well as external beam radiation in eyes of patients with hereditary retinoblastoma.

The study is based on a retrospective analysis of data from 200 patients with hereditary retinoblastoma. Apart from four unilateral cases with a positive family history all patients had bilateral disease; 229 appeared suitable for conservative treatment while 167 eyes had to be enucleated. Primary local treatment was performed in 102 eyes, while 127 eyes received primary external beam radiation using a linear accelerator. Follow-up was adjusted by life tables, with 75% of the patients being observed longer than 2 years. Using life-table statistics new and recurrent tumors were found in 41% of all patients and in 95% of these cases they were noted within 26 months after initiation of therapy. Among eyes treated with primary external beam radiation new and recurrent tumors were observed significantly less frequently when 50 Gy (22% compared with 49% after 40 Gy) and a highly accurate beam alignment technique (22% compared with 48% after alignment to the outer bony canthus) were applied. The incidence of recurrent tumors following primary local treatment did not differ significantly with regard to the application of either photo- or cryocoagulation (28% vs 33%), while no recurrence was observed among tumors that were suitable for primary treatment using ruthenium or cobalt plaques.

Brachytherapy↗
PubMed1990

Clinical results and the Essen concept of TBI.

Total body irradiation (TBI) prior to bone marrow transplantation (BMT) is applied for treatment of 230 patients in the period 1975-1988. The clinical results of 169 patients treated by four different TBI dosage and treatment techniques are analysed. The risk of leukemic relapse is low after fractionated TBI (9%) as well as after single dose TBI (14%). The lowest frequency of interstitial pneumonitis (21%) occurred when the patient translation technique was used for fractionated homogeneous pa/ap TBI with 10 Gy (8 Gy lung dose) in 4 fractions in 4 days. Prophylaxis of GVHD and the modus of protective environment were two other factors which influence the risk of IP.

Adult↗
PubMed1990

Radiation response in 10 high-grade human soft tissue sarcoma xenografts to photons and fast neutrons.

From a panel of 48 human soft tissue sarcomas growing as permanent xenografts, 10 tumor lines (five leiomyosarcomas, three malignant fibrous histiocytomas, two neurofibrosarcomas) have been selected to determine the radiation response to photons and fast neutrons. Using the specific growth delay (SGD) as an end-point, considerable variability of inherent radiosensitivity was observed. Isoeffective radiation doses varied by a factor of 27 for photons and of 9.4 for neutrons at a specific growth delay level of 0.5. The heterogeneity of the relative biological effectiveness (RBE) at this specific growth delay-level differed by a factor of 8. Relative biological effectiveness values for clamped tumors exceeded those of the normal tissues (RBE approximately 3) in 6 out of 10 tumor lines. Assuming a ratio of 0.5 for oxygen enhancement ratio-values of neutrons and photons, a therapeutic gain for neutrons existed in 4 out of 10 tumor lines under oxic conditions. No correlation between volume doubling times and relative biological effectiveness was seen.

Animals↗
PubMed1990

Carcinoma of the nasopharynx. The significance of lymphocytic infiltration.

From 1974 to 1985, 76 patients with nasopharyngeal carcinoma (NPC) received irradiation with curative intent and 14 with palliative intent in our department. Of the 76 patients, 59 presented with UICC stage IV. The 5-year actuarial survival rate was 41% and the relapse-free survival rate (RFS) 45%. The slides were reviewed according to the World Health Organization (WHO) histologic classification, also taking into account the degree of lymphocytic infiltration according to its Cologne modification. Undifferentiated carcinoma and non-keratinizing carcinoma had similar 5-year RFS (47 and 44% respectively). Patients with major lymphocytic infiltration in the tumor presented with younger median age, with smaller primary tumors and with more advanced neck disease than the other patients. There was, however, no obvious association between the degree of lymphatic infiltration in the tumor and the prognosis. Patients with major lymphocytic infiltration had a 5-year RFS of 44%, versus 49% for patients without such infiltration.

Adolescent↗
PubMed1990

[Adjuvant radiotherapy of rectal cancer].

Evaluation and refinement of surgical techniques in rectal carcinoma have reduced the rate of local recurrences. Nevertheless recurrence it remains high at more than 20% in patients with extensive infiltration of perirectal tissues and cures are an exception. Overview of many years of experience with adjuvant radiotherapy shows that local recurrence rate can be reduced and survival the rate improved.

Combined Modality Therapy↗
PubMed1990

Xenografts of five human leiomyosarcomas: radiation response after 60cobalt- and d(14)+Be neutron single doses.

Five permanently established xenograft lines of human soft tissue sarcomas were irradiated with single doses of 5.8 MeV d(14)+Be neutrons and of 60Co rays, respectively, at several dose levels to generate dose response relationships. The tumors were clamped ten minutes prior to and during irradiation to induce uniform hypoxia. All tumours were previously characterized by means of histomorphology, tumour doubling times (DT's), DNA-index and enzyme pattern of the lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (GPD). According to these criteria, three out of five leiomyosarcomas were identical referring to the biopsy of origin, whereas two had changed in successive passages. For the different tumour lines, specific growth delays ranged from 0 to 8.7 after 5.3 Gy neutrons and from 0 to 11.4 after 16 Gy60Co, respectively. In terms of radiosensitivity for different single doses and irradiation qualities, a highly significant overall correlation (rs = 0.82 +/- 0.06) was found for the ranking of the tumours with respect to the growth delay and specific growth delay endpoints. No correlation was found between tumour doubling times and the relative biological effectiveness (RBE). In general, calculated RBE-values decreased with increasing effect level. For the five tumour lines, RBE-values ranged from 1.6 to 12.7 and 2.0 to 4.4 at specific growth delays of 0.5 and 2.0, respectively, under acutely hypoxic conditions. These results indicate a potential advantage for neutrons in a subgroup of human soft tissue sarcomas compared with sparsely ionising irradiation.

Animals↗
PubMed1990

Neutron boost irradiation of soft tissue and chondrosarcomas at the West German Tumour Centre in Essen.

In this retrospective study, the results of postoperative neutron boost therapy for 40 soft tissue- and 18 chondrosarcomas are presented. In 65.5% and 34.5% of all cases, microscopic to macroscopic tumour residual was left postoperatively. Locally advanced and moderate to highly malignant tumours were found at surgery in 81% and 69%, respectively. Except for seven patients with a whole series of neutrons to 16 Gy, the other cases were treated with initially 40 to 50 Gy photons and a subsequent neutron boost of 4 to 6 Gy. The median follow-up was 29.3 and 36.2 months for the soft tissue- and chondrosarcomas. The actuarial three-year local control and overall survival rates were 69.3% and 91% for soft tissue- vs. 55.6% and 62.9% for chondrosarcomas. With regard to the extension of surgery (microscopic or macroscopic residual), local control rates of 80% and 60% for soft tissue- vs. 62.5% and 40% for chondrosarcomas were observed. The overall local failure rate was 32.8% with a median disease-free interval of ten respectively eleven months for soft tissue and chondrosarcomas. 17 out of 19 local recurrences were due to inadequate irradiation portals for the neutron boost or to insufficient total doses in the initially treated photon target volume.

Actuarial Analysis↗
PubMed1990

[A low-cost localization technique for high-dose-rate afterloading applicators].

For radiation safety control radiotherapy today needs a method to check the correct position of a HDR-gynecological applicator before afterloading treatment. At the university clinic in Essen, West Germany, a surgical c-X-ray plant was used for the construction of an orthogonal X-ray-photograph plant, which combines illumination and photographs as localisation technique.

Brachytherapy↗