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W Budach

Publications and source records attributed to W Budach.

At least 73 records · Page 4Linked to original sources
PubMed1993

Quantitative comparison between the transplantability of human and murine tumors into the subcutaneous tissue of NCr/Sed-nu/nu nude and severe combined immunodeficient mice.

In previous reports, nude mice have demonstrated residual immunoreactivity against xenografts. Severe combined immunodeficient (SCID) mice lack functional T- and B-cells. These animals are expected to be better hosts in which to perform preclinical studies on human tumors. The purpose of this study is to quantitate the advantage of SCID mice over nude mice in terms of transplantability of human and murine tumors and the importance of residual immunity in SCID mice. The transplantation assays are described by an assay based on the number of tumor cells required to transplant tumor into 50% of recipients (TD50). Seven human tumors of different histology and four murine tumor cell lines were used. Serial 2-10-fold dilutions of cells were injected (0.1 ml) into the flanks of normal and whole-body irradiated WBI nude and SCID mice. The results showed that in 6 of 6 human tumor cell lines studied, TD50S for SCID mice were 2.4 to 200 times lower than that of nude mice (significant in 5 cell lines). In contrast, in 2 of 3 murine tumors, TD50S in WBI SCID mice were significantly higher than that found in nude mice. When SCID and nude mice received WBI, TD50S were lower than those of nonirradiated animals in 5 of 5 xenografts (significant in 2 cell lines for nude mice and in 5 cell lines for SCID mice). We concluded that WBI SCID mice are significantly better recipients of human tumor xenografts than nude mice. There is a factor of 10-1625 gain in TD50S in favor of the WBI SCID mice when compared to nonirradiated nude mice. WBI has, however, an important effect on SCID mice which may suggest a detectable residual immunoreactivity, perhaps due to natural killer cells. These data demonstrate that WBI SCID mice are better models for human tumor transplantation that nude mice and, although WBI at 6 Gy suppressed significantly the immune system of nude mice, a certain level of immunoreactivity against xenografts is still maintained.

Animals↗
PubMed1993

Quantitative comparison between the transplantability of human and murine tumors into the brain of NCr/Sed-nu/nu nude and severe combined immunodeficient mice.

We have demonstrated (A. Taghian et al., Cancer Res., 53: 5012-5017, 1993) that the take rate of human xenografts in the s.c. tissue of severe combined immunodeficient (SCID) mice is significantly higher than that of nude mice. Earlier, this laboratory reported that the transplantability of tumor xenografts was significantly higher for intracranial (i.c.) injection than for s.c. injection in nude mice. The purpose of this study is to assess: (a) the relative i.c. transplantability of human and murine tumors in comparison with s.c. tissue in SCID mice; (b) the relative i.c. transplantability in SCID mice in comparison to nude mice; and (c) the influence of whole-body irradiation on i.c. transplantability of SCID and nude mice. The assay based on the number of cells required to transplant tumors into 50% of recipients (TD50) was used to describe the transplantability assays. Five human and four murine tumor cell lines were used. Concurrent TD50 assays were performed i.c. in whole-body irradiated and nonirradiated SCID and nude mice. Serial 2-10-fold dilutions of cells were injected in a 10-microliters volume into the right parietal lobe 3 mm below the skin. The results showed that in all tumors studied the i.c. TD50S were significantly lower than the s.c. TD50S by a factor of 1.7-1580. The average enhancement ratio (s.c. TD50/i.c. TD50) in nude mice was twice that in SCID mice. No significant difference was found between the i.c. TD50S in SCID and in nude mice, contrary to the significant difference in s.c. TD50S between both strains of mice (A. Taghian et al., Cancer Res., 53: 5012-5017, 1993). Whole-body irradiation did not significantly affect the i.c. TD50 in nude mice; however, it did affect two of three xenografts in SCID mice. In conclusion, despite the significantly lower s.c. TD50S of human xenografts in SCID mice, i.c. TD50S were almost similar to those of NCr/Sed-nu/nu nude mice. This suggests the presence of different immunoreactivities between nude and SCID mice in s.c. transplantability; however, for i.c. transplantability, nude mice behaved equally as well as SCID mice. The significant enhancement ratio in SCID mice is further evidence that this strain of mice displays a residual systemic immunoreactivity, although the immunoreactivity is significantly lower than that of nude mice.

Animals↗
PubMed1993

Impact of stromal sensitivity on radiation response of tumors.

BACKGROUND: Irradiation of tumors causes the death of both parenchymal tumor cells as well as normal tissue stromal cells (e.g., endothelium, connective tissue). However, it has been difficult to distinguish the contributions to overall tumor response after irradiation from the two compartments. The development of the severe combined immunodeficient (SCID) mouse provides a model in which the contribution of stromal cell responses to ionizing radiation to overall tumor response can be defined, because its normal tissue cells are extremely radiosensitive. Therefore, the results of irradiation of tumors in radiation-sensitive (SCID) and radiation-resistant hosts can be compared, and the contribution of the normal tissue stroma clarified. PURPOSE: Our purpose was to investigate the effects of radiation-induced stromal cell damage on tumor cell death, using tumor growth delay (GD) and local control (complete and permanent regression of the irradiated tumor) as end points. METHODS: Tumor GD and local control experiments were performed in SCID, athymic, and C3H mice. Sixty SCID and 60 nude mice for each of three human tumor cell lines (HGL9, HSTS26, HCT15) and for each of five murine cell lines (FSC1, FSC2, FSM1, FSM2, E01) and 60 SCID and 60 C3H mice for the FSa2 spontaneous C3H sarcoma were studied. Neoplasms were produced by injection of 10(6) cells from in vitro tissue cultures into the flanks of donor mice; after tumors had grown, experimental neoplasms were produced by transplanting 2- to 3-mm fragments into recipient mice. Animals were randomly assigned to various groups when tumors reached average volumes of 120 mm3. Graded, single-dose x irradiations (15-115 Gy, dose rate about 7 Gy/min) were given under acutely hypoxic conditions. Tumors were scored one to two times per week until recurrence. RESULTS: The x-ray doses needed to achieve local control in 50% of the animals (tumor control doses, TCD50) ranged from 45.1 to 58.0 Gy for human tumors and from 36.3 to 114.0 Gy for murine tumors. On average, the TCD50 values in SCID mice were only about 3.5% lower than values in nude or C3H mice. The amount of GD defined at 66% of the TCD50 for the various groups was, however, 27% longer in the SCID mice (P = .004). CONCLUSIONS: While the three-fold higher radiation sensitivity of the normal tissue stromal cells in the SCID mice did not alter the percentage of tumors controlled by x irradiation in the SCID mouse hosts as compared with other hosts, there appear to be significant differences in GD. Radiation-induced stromal cell damage does not significantly contribute to tumor cell death; however, it can prolong the interval of tumor regression.

Animals↗
PubMed1993

Intrinsic radiation sensitivity may not be the major determinant of the poor clinical outcome of glioblastoma multiforme.

PURPOSE: Many radiobiologic mechanisms may contribute to the clinical radiation resistance of Glioblastoma Multiforme. One of them is considered to be an unusually low intrinsic radiation sensitivity. This is a collaborative study between three laboratories to evaluate the intrinsic radiation sensitivity of 85 cell lines derived from human malignant gliomas as the major cause of the poor clinical results of radiation treatment to these tumors. METHODS AND MATERIALS: Fifty-one cell lines were early passage. The distribution by histologic type was: 58 glioblastoma, 17 anaplastic astrocytoma, six oligodendroglioma and four astrocytoma grade 2. The intrinsic radiation sensitivity will be expressed by the surviving fraction at 2 Gy (SF2). The SF2 has been determined for single dose irradiation for cell lines on exponential phase, under aerobic conditions, growing on plastic. The patient age, Karnofski Status, histological grade, survival, dose of irradiation for 50 patients are investigated for correlation with SF2 of the corresponding newly established cell lines. RESULTS: The mean SF2 of the 85 cell lines was 0.46 (0.12-0.87). The mean SF2 by histologic type was 0.50, 0.34, 0.54 and 0.38 for glioblastoma, anaplastic astrocytoma, oligodendroglioma and astrocytoma grade 2 cell lines, respectively. No correlation was found between SF2 and the patient age or Karnofski status. The difference in SF2 between the 58 glioblastoma and 17 anaplastic astrocytoma cell lines was significant p = 0.002. The difference in actuarial survival between glioblastoma and anaplastic astrocytoma patients was borderline of significance (p = 0.08). The difference in SF2 of cell lines derived from these two groups of patients was of borderline significance (p = 0.08). The difference in radiation sensitivity for anaplastic astrocytoma and glioblastoma cell lines was clearly reflected in the difference in survival for the two groups of patients from where the cell lines were derived. However, no correlation was found between SF2 and survival within each grade. In a multivariate analysis the age, grade and Karnofski status were found to be significant prognostic values for survival with a p values of 0.032, 0.03 and 0.038, respectively, however, the ln SF2 was not significant (p = 0.40). The mean SF2 of the 6 oligodendroglioma cell lines (0.54) was comparable to that of glioblastoma multiforme (0.50). The high SF2 for oligodendroglioma does not accord with the much better clinical outcome of these tumors. CONCLUSIONS: These data on 85 malignant glioma cell lines show a very broad distribution of SF2 values for irradiation in vitro. SF2 reflected the difference in sensitivity between AA (Grade 3) and GBM (Grade 4). This may suggest that the parameter SF2 is useful to discriminate between the sensitivity of different grades or types of histology in vitro. However, SF2 was not a predictor of the clinical outcome on individual basis for malignant gliomas. The in vitro studies will need to be supplemented by physiologic characterization of the tumors in vivo. Such conclusions would limit the predictive value of current radiation sensitivity assays based on in vitro dose-survival measurement for at least high grade malignant gliomas.

Astrocytoma↗
PubMed1993

The TCD50 and regrowth delay assay in human tumor xenografts: differences and implications.

The response to irradiation of five human xenograft cell lines--a malignant paraganglioma, a neurogenic sarcoma, a malignant histiocytoma, a primary lymphoma of the brain, and a squamous cell carcinoma--were tested in nude mice. All mice underwent 5 Gy whole body irradiation prior to xenotransplantation to minimize the residual immune response. The subcutaneous tumors were irradiated at a tumor volume of 120mm3 under acutely hypoxic conditions with single doses between 8 Gy and 80 Gy depending on the expected radiation sensitivity of the tumor line. Endpoints of the study were the tumor control dose 50% (TCD50) and the regrowth delay endpoints growth delay, specific growth delay, and the tumor bed effect corrected specific growth delay. Specific growth delay and corrected specific growth delay at 76% of the TCD50 was used in order to compare the data to previously published data from spheroids. The lowest TCD50 was found in the lymphoma with 24.9 Gy, whereas the TCD50 of the soft tissue sarcomas and the squamous cell carcinoma ranged from 57.8 Gy to 65.6 Gy. The isoeffective dose levels for the induction of 30 days growth delay, a specific growth delay of 3, and a corrected specific growth delay of 3 ranged from 15.5 Gy (ECL1) to 37.1 Gy (FADU), from 7.2 Gy (ENE2) to 45.6 Gy (EPG1) and from 9.2 Gy (ENE2) to 37.6 Gy (EPG1), respectively. The corrected specific growth delay at 76% of the TCD50 was correlated with the number of tumor rescue units per 100 cells in spheroids, which was available for three tumor lines, and with the tumor doubling time in xenografts (n = 5). The TCD50 values corresponded better to the clinical experience than the regrowth delay data. There was no correlation between TCD50 and any of the regrowth delay endpoints. This missing correlation was most likely a result of large differences in the number of tumor rescue units in human xenografts of the same size.

Animals↗
PubMed1993

[Malignant paragangliomas--the results of radiotherapy in 6 patients].

Between February 1984 and May 1989, six patients (four male, two female) with malignant paragangliomas of the carotid body (n = 4) and glomus jugulare (n = 2) were irradiated in the Department of Radiation Oncology at Essen University. All patients had macroscopic (residual) tumor at the start of treatment. Five out of six paragangliomas had to be considered malignant, since histological lymph node involvement or distant metastasis was confirmed. In the sixth case extra- and intracranial tumor growth was observed. Total doses between 40 and 55 Gy using cobalt 60, 10 or 15 MeV photons were administered. Radiation therapy was canceled at 30.6 Gy in one patient because of multiple distant metastasis. Three out of four patients, who received curative treatments, were locally controlled (25 to 91 months). A local recurrence in one patient was detected 18 months after irradiation; this patient died of distant metastasis 23 months after treatment. In one out of two palliatively irradiated patients, local control could be achieved until the patient died of distant metastasis twelve months after treatment. Grade III- or grade IV-treatment toxicity was not observed. Radiation therapy of malignant paragangliomas with doses between 45 and 54 Gy in five to six weeks is an effective treatment with low toxicity and should be preferred to surgery in glomus jugulare and advanced carotid body tumors.

Adult↗
PubMed1993

In vitro split-dose recovery of glioblastoma multiforme.

Glioblastoma multiforme is among the most clinically resistant tumors to radiation. This resistance may be due to several different factors, such as a low intrinsic radiation sensitivity, a high recovery capacity, an increased number of clonogens, and a high hypoxic fraction. Previously, we have demonstrated a very wide range of intrinsic radiation sensitivities of cells of glioblastoma multiforme cell lines in vitro after single-dose irradiation. That is, the cells of some glioblastoma multiforme cell lines were quite sensitive, while for others the sensitivity of glioblastoma multiforme was among the lower range of sensitivities reported in the literature. This finding indicates that inherent cellular radiation sensitivity is not the sole determinant of the in vivo response of glioblastoma multiforme tumors. In this report, we evaluate the role of split-dose recovery determined in vitro in relation to the poor clinical outcome of glioblastoma multiforme. Cells of seven early-passage glioblastoma multiforme cell lines and six cell lines derived from tumors of a type frequently treated successfully (two squamous cell carcinomas of head and neck, three breast cancers, and one low-grade astrocytoma cell line) were studied. The in vitro split-dose recovery has been measured using colony formation as an end point. The cells were maintained at 37 degrees C for a period of 6 h between the doses of radiation. Results are presented in terms of a recovery ratio: the ratio of the mean inactivation dose of split-dose radiation to that of single-dose radiation. The data show significantly higher recovery ratios for glioblastoma multiforme than for the other types of histology; however, glioblastoma multiforme showed a wide range of recovery ratios, varying from 1.12 to 2.02. This indicates that cells of some glioblastoma multiforme cell lines exhibit minimal split-dose recovery. No correlation was found between the recovery ratio and the intrinsic radiation sensitivity of the cell lines studied. From these data, we conclude that the recovery capacity may not be the major determinant of the clinical radiation resistance of some glioblastoma multiforme.

Cell Survival↗
PubMed1993

Drug- and radiation-induced resistance in a human neurogenic sarcoma xenografted in nude mice.

The in vivo development of radiation- and doxorubicin-induced resistance was studied in a chemosensitive and radiosensitive human neurogenic sarcoma (Essen neuroectodermal tumor line 2) xenografted in nude mice. Dose-response curves were generated for the parent tumor line, and growth delay (GD) and specific growth delay (SGD) were the study end points. An intravenous injection of doxorubicin at 10 mg/kg, the lethal dose for 10% of the study population (LD10) in nude mice, and a single dose of 12 Gy radiation were determined to be isoeffective and were thus maintained for all subsequent treatments. For the induction of resistance to both treatment modalities, regrowing tumors were transplanted into successive generations of nude mice and retreated. This procedure was repeated 13 and 9 times, respectively, for the doxorubicin and radiation treatments. The response was monitored in all passages. As compared with the parent tumor line, a 50% decrease in SGD was observed following 3.9 and 8.5 treatments with doxorubicin and radiation, respectively. Following four treatments with doxorubicin, SGD in tumors crossed over to radiation therapy declined by 50%. Radiation therapy, on the other hand, caused significant reductions in GD and SGD in tumors that were subsequently exposed to doxorubicin, but it did not induce a 50% decline in response. Overexpression of P-170-glycoprotein was not observed for either treatment modality. The data suggest that treatment with doxorubicin or radiation can potentially induce resistance to subsequent continued or crossover treatment and that this resistance develops gradually. The lack of P-170-glycoprotein over-expression in the resistant cell lines indicates the existence of alternative pathways that may lead to resistance.

Animals↗
PubMed1992

Tumors arising in SCID mice share enhanced radiation sensitivity of SCID normal tissues.

We addressed the question of whether cancers arising in an abnormally radiation sensitive normal tissue are also abnormally sensitive to ionizing irradiation. Germ line mutation-carrying mice with an enhanced radiation sensitivity of the normal tissue, the severe combined immunodeficient (SCID), and normally radiation sensitive mice (C3H) were used to study the sensitivity of normal and tumor tissues in vivo and in vitro. The lethal dose for 50% of the irradiated animals after single dose whole body irradiation was 2.6-fold higher in C3H compared to SCID mice. The dose for an isoeffective acute skin reaction after single dose irradiation was end point dependent 1.7 to 3.7 times higher in C3H than in SCID mice. Embryonic fibroblast and methylcholanthrene induced soft tissue sarcomas derived from C3H and SCID mice were established in vitro and colony-forming assays after single dose irradiation were carried out. Choosing mean inactivation dose as the end point, SCID fibroblast lines were 3.0-fold and SCID tumor cell lines 2.7-fold more radiation sensitive than C3H fibroblast lines and C3H tumor cell lines. Tumor control and growth delay assays for 110-mm3 tumors were used to compare the radiation sensitivity of SCID and C3H tumors in vivo. The doses for 50% local tumor control and a growth delay of 40 days were 2.6 times higher in C3H tumors compared to SCID tumors. Tumors arising in an abnormally radiation sensitive normal tissue are also sensitive to irradiation. The difference in radiation sensitivity of normal tissues predicted the difference in tumor tissues in these two murine systems.

Animals↗
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

[Radiotherapeutic strategies for soft tissue sarcomas in adults].

Soft tissue sarcomas account for under 1% of all cancers in adults. Most soft tissue tumours are benign, only about 1% being characterized clinically and histomorphologically as malignant neoplasms. Since these tumours are often treated by excisional biopsies without any further diagnostic imaging, precise planning of postoperative irradiation therapy is often difficult to achieve. Therefore, all soft tissue tumours with a short history should be regarded as malignant until the contrary has been proven. In general, the mode of tumour resection should be postponed until CT or MR diagnosis is complete and a biopsy of the tumour has been carried out. Whereas benign lesions need only marginal tumour resection, malignant lesions require considerable safety margins. In soft tissue sarcomas of the extremities, which account for 50-60% of all sarcomas, a wide local resection followed by postoperative irradiation with about 66 Gy can guarantee local control rates above 80% and preserve the function of the limb. Radical surgery alone can achieve the same local control, but without the high level of functional integrity. In the case of marginally resectable tumours, preoperative irradiation can induce partial tumour remission and thus allow definitive limb-sparing tumour resection. Recently, multimodal and neoadjuvant therapeutic strategies have been developed. The efficacy of these experimental strategies is not yet proven.

Adult↗
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↗
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

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

Methods for analysis of censored tumor growth delay data.

Growth delay times of experimental tumors after subcurative therapy may be censored because of intercurrent death of the host animals, limitations of the follow-up period, or the number of cured tumors. Under the general assumptions of log-normally distributed data and independence of the censoring event and the therapy effect, it is shown using computer simulations that the estimate of the median growth delay according to the product limit method of Kaplan and Meier, which allows inclusion of censored data, is unbiased. Omission of censored growth delay times from incomplete accrued data often leads to biased estimates. The power of statistical tests for qualitative comparison of two therapy groups with incomplete sets of data from growth assays was also studied. In the absence of censoring, the power of the different tests is about the same. At higher censoring rates of 40%, however, tests applicable to censored data (log-rank test, Gehan-Wilcoxon test) have a markedly higher power than tests applied to the reduced set of complete observed growth delays (mu test, t test). Although complete observation of tumor regrowth should be strived for, growth delay experiments with very delicate animal tumor models can easily result in censored data. The methods presented permit quantitative and qualitative analysis of growth delay data up to a censoring rate of over 30%, if growth delays and censoring events are independent.

Animals↗