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Biomedical subjects

M Stuschke

Publications and source records attributed to M Stuschke.

At least 91 records · Page 5Linked to original sources
PubMed1994

[Surgery of locally advanced non-small-cell bronchial cancer after intensive preoperative chemo-/radiotherapy].

From March 1991 to June 1993 50 patients with local advanced NSCLC (mediastinoscopy obligatory) have been entered into an ongoing trial with preoperative chemotherapy and simultaneous chemo-/radiotherapy, followed by re-mediastinoscopy and surgery. Clinical response rates after chemotherapy amounted to 66.8% after chemo/radiotherapy 77.5%, no severe toxicity was observed. 36 patients ultimately underwent operation, 29 with a curative, 5 with a palliative resection and 2 with an explorative thoracotomy. Pathological complete remission rates of the primary tumor were found in 11 (32.3%), R0-resection in 18 (52.9%) and R1-resection in 5 (14.7%) cases. Sterilisation rates of mediastinal nodes were found in 86.3% of N2 tumors and 66.6% of N3 tumors. Median survival time ranged between 21 months for stage III a and 16 months for III b disease. This intensive preoperative neoadjuvant treatment is tolerable and effective, the requirements for a randomised comparative trial was met.

Adult↗
PubMed1994

A time-saving system for irradiations of experimental tumors.

PURPOSE: Experimental in vivo radiotherapy frequently aims at the imitation of clinically applied fractionation schedules. However, the reliability of the anesthetic procedure and limited access to the treatment machines in clinical departments are major factors complicating the practical realisation of the experiment. Therefore, a reliable and time saving system for irradiations of xenografted tumors has been developed, which allows repeated irradiations, even in relatively short intervals available for experimental irradiations. MATERIAL AND METHODS: The system presented here consists of an acrylic distributor for an anesthetic gas mixture employing enflurane (Ethrane) in the center of the set-up. Ten mice are positioned radially around the midpoint of the set-up so that they can be irradiated simultaneously. The xenotransplanted tumors growing on the right hind leg of mice are placed in a predefined position, which was found to be of advantage in order to position the tumors for fractionated treatments in identical setting. Tumor-bearing mice are irradiated with 15 MeV photons generated by a linear accelerator at a dose rate of 2.5 Gy/min. One of the significant feature of the setup is the ability to irradiate in acute hypoxia which is obtained by use of an integrated tourniquet. The dose modifying effects of different gases can be investigated by simply using them as carrier for the enflurane. RESULTS: With the use of the set-up several different experiments were performed so far. At most ten fractions were given, one fraction per day. Even after these repeated treatment the loss of animals due to narcosis was less than 2%. The dose variation within the treatment field was found to be less than 4% as measured with TLD dosimetry. The remaining body of the mice is shielded effectively from the direct beam as the whole body dose of mice is 8% of the total tumor absorbed dose. The efficacy of the tourniquet technique for acute hypoxic irradiations was illustrated with the use of 99mTc-labelled albumin showing a complete stop of blood flow in the clamped leg. The steep dose-response curve obtained for single dose irradiation of a neurogenic sarcoma is based on the physical and experimental precision which can be reached with the technique suggested here. CONCLUSION: Due to the high dose rate and the possibility to irradiate ten animals simultaneously the set-up introduced here is greatly time saving. The versatile applicability makes the new set-up a valuable tool for tumor radiobiology.

Anesthesia, Inhalation↗
PubMed1993

Radioresponsiveness of human glioma, sarcoma, and breast cancer spheroids depends on tumor differentiation.

PURPOSE: Differences in the intrinsic radiosensitivity within and between different tumor classes have been noticed for human tumor cell lines using the clonogenic assay. By far, most of the cell lines studied up to now were derived from poorly differentiated tumors. In this study, the influence of tumor differentiation on the radiation doses necessary to control 50% of small oxic spheroids (SCD50) was determined. Evidence of a distinct dependence of radioresponsiveness on tumor progression provides a background for an investigation of the underlying mechanisms. METHODS AND MATERIALS: Spheroids were aggregated from 1000-1500 cells in agarose coated 24 multi-well plates. Their diameters ranged from 156 to 405 microns, depending on the cell line. Spheroids were irradiated with graded 60Co single doses using spheroid control as end point and a minimum follow-up period of 3 months. RESULTS: Cell lines from three low grade gliomas and 10 malignant gliomas were studied in the spheroid control assay. The group mean SCD50 values were 6.1 +/- 1.6 Gy and 13.1 +/- 3.3 Gy, respectively. Four cell lines from grade 2 soft tissue sarcomas had a mean SCD50 value of 6.2 +/- 0.5 Gy and one undifferentiated sarcoma line of 11.0 Gy. Three well-differentiated breast cancer lines expressed the cell adhesion molecule E-cadherin, had an epithelioid morphology in monolayer culture, were estrogen receptor positive or contact inhibited in multicellular spheroids. Two undifferentiated breast cancer lines had a fibroblastoid morphology and were marker negative. The mean SCD50 value of the former was 10.5 +/- 1.0 Gy while that of the undifferentiated lines was 14.8 +/- 2.8 Gy. Analysis of variance revealed a significant effect of the tumor type as well as the grade of dedifferentiation on the SCD50 after irradiation with one fraction or 2Gy/fraction. The surviving fractions at 2 Gy (SF2), obtained from the spheroid control rates after different fractionation schedules by approximation of the linear quadratic model assuming Poisson statistics were significantly dependent on tumor type (p = 0.001, ANOVA F-test) but not on tumor differentiation (p = 0.27). The alpha/beta ratios did not depend on tumor type (p = 0.08, ANOVA F-Test) but significantly increased with the grade of tumor cell dedifferentiation (p = 0.03). CONCLUSION: The spheroid model is suitable for measuring the radioresponsiveness of differentiated cell lines with very low colony forming efficiencies. Tumor cell differentiation is an important factor for the radioresponsiveness and recovery capacity of human tumor cells.

Breast Neoplasms↗
PubMed1993

Deep regional hyperthermia: comparison between the annular phased array and the sigma-60 applicator in the same patients.

PURPOSE: Several institutions have accumulated clinical experience with the annular array as well as with the Sigma applicator. There exist only limited data in comparison of both heating devices possibly favoring the annular array over the Sigma applicator with regard to tumor temperatures and acute toxicity. The objective of this study was to record temperature distributions at identical sites in tumor and normal tissue in the same patients treated with each device. METHODS AND MATERIALS: Eighteen patients with advanced pelvic tumors were treated on successive occasions with regional hyperthermia using the annular phased array applicator usually driven at 60-80 MHz or the Sigma applicator usually driven at 70-90 MHz. In all patients detailed thermal mapping and temperature analysis for tumor and normal tissues could be performed. RESULTS: Regardless the device used the acute toxicity was treatment limiting in nearly 50% of the treatments. Systemic stress was treatment limiting in 30% of the treatments with both devices although systemic parameters (core temperature, heart rate, changes in blood pressure) were higher with the annular array. The overall mean minimum, average and maximum tumor temperature observed were 39.5 +/- 1.0 degrees C, 40.9 +/- 1.4 degrees C, 42.7 +/- 2.3 degrees C for the annular array and 39.3 +/- 0.9 degrees C, 40.9 +/- 1.4 degrees C, and 42.5 +/- 1.7 degrees C for the Sigma applicator. The time-averaged temperatures achieved in 20% (T20), 50% (T50) and 90% (T90) of all measured sites were 41.7 +/- 2.1 degrees C, 40.8 +/- 1.4 degrees C, 39.9 +/- 1.2 degrees C for the annular array and 41.7 +/- 1.4 degrees C, 41.0 +/- 1.3 degrees C, and 40.1 +/- 1.0 degrees C, for the S-60. The difference was not statistically significant. With regard to normal tissue temperatures a trend to higher maximum temperatures in the deep muscle and fat tissue was evident for the Sigma applicator. The overall minimum and average normal tissue temperatures in the deep muscle and fat tissue and the rectum and the time-averaged temperatures achieved in 20% (T20), 50% (T50) and 90% (T90) of the measured sites differ not statistically significant. CONCLUSION: These results indicate that there continue to be unresolved limitations in achieving temperature elevation in deep seated tumors of the pelvis with radiative coherent EM wave techniques using amplitude and phase steering capabilities without any special optimization procedure.

Adult↗
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

Thermoradiotherapy in locally advanced deep seated tumours--thermal parameters and treatment results.

From October 1987 to December 1990 a total of 37 patients with deep seated tumours of the pelvis (n = 34), the abdomen (n = 2), or lower leg (n = 1) were treated with radiotherapy and regional hyperthermia. Hyperthermia was produced by the BSD-1000 system and the annular phased array (AA) applicator usually driven at 60-80 MHz, or the BSD-2000 system and the Sigma-60 (S 60) applicator usually driven at 70-90 MHz. Detailed thermal mapping and temperature analysis was performed on 29 patients. The overall mean maximum, average and minimum temperature observed was 42.9 +/- 2.4 degrees C, 40.9 +/- 1.5 degrees C, and 39.3 +/- 0.9 degrees C for all treatments. The time-averaged tumour temperatures achieved in 20%, 50% and 90% of all measured temperature sites were 41.8 +/- 2.1 degrees C (T20), 40.9 +/- 1.6 degrees C (T50), and 39.9 +/- 1.2 degrees C (T90). In addition, the overall mean maximum, average and minimum temperature measured in normal tissue was 42.4 +/- 1.4 degrees C, 40.6 +/- 1.0 degrees C, and 39.2 +/- 0.9 degrees C. The time averaged normal tissue temperatures achieved in 20%, 50% and 90% of all measured temperature sites were 41.3 +/- 1.1 degrees C, 40.6 +/- 1.1 degrees C, and 39.6 +/- 1.0 degrees C. In 36 assessable patients, the overall objective response rate was 31%: 2 complete responses (CR) and 9 partial responses (PR).

Adult↗
PubMed1993

Spheroid control of malignant glioma cell lines after fractionated irradiation: relation to the surviving fractions at 2 Gy and colony forming efficiencies in a soft agar clonogenic assay.

Spheroid control doses (SCD50) were determined for ten human glioma lines after fractionated irradiation under oxic conditions. In addition, SF2 values and colony forming efficiencies (CFE) were measured in a soft agarose clonogenic assay. A significant relationship existed between the SCD50 values and the SF2-CFE data pairs (p = 0.01) but the SCD50 values were higher than expected from the SF2 and CFE values. This comparison shows the influence of environmental factors (different in both model systems) on reproductive tumour cell death after irradiation.

Cell Aggregation↗
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

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

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

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↗
PubMed1991

Angioplasty of renal arteries: a report of ten year's experience.

Report of PTA of renal arteries in 288 patients. Primary results show good to optimal dilatation of the arteries (60.6% to 78.6%). One third of all cases achieved optimal blood pressures. In about 40% antihypertensive drugs had to be administered, in about 30% blood pressure remained unchanged although PTA was effective. PTA of renal arteries is the best method of treating renal hypertension, also because of the low rate of complications.

Angioplasty, Balloon↗
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

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↗