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Biomedical subjects

J Overgaard

Publications and source records attributed to J Overgaard.

At least 163 records · Page 9Linked to original sources
PubMed1993

[Malignant parotid tumors. Therapeutic results and prognosis in 110 consecutive patients].

The UICC 1987 TNM classification system was used to retrospectively analyze the treatment results and prognostic factors in 110 consecutive patients diagnosed and treated from 1970 to 1986. Treatment consisted of surgery, radiotherapy, or a combination. Malignant mixed tumours were seen in 28% of the patients, mucoepidermoid tumours in 18%, adenoid cystic tumours in 15%, acinic tumours in 13%, undifferentiated tumours in 11%, adenocarcinomas in 10%, and other types in 5%. Ten-year corrected survival was 52%, and significant differences in survival were found between: 1. patients with disease stage I-IV (I: 85%, II: 69%, III: 43%, IV: 14%); 2. those with local tumour extension (34%) and without local tumour extension (79%); 3. patients with facial nerve palsy (0%) and without facial nerve palsy (57%); 4. those with low- or intermediate-grade tumours (69% combined) and those with high-grade malignant tumours (30%). Forty-five percent of the patients were cured after primary treatment, as were an additional 22% of those treated for local or neck node recurrences. It is concluded that there is a good correlation between TNM classification of UICC 1987 (stage and local extension of tumour) and prognosis, and that facial nerve palsy and grade of malignancy are important prognostic factors.

Adolescent↗
PubMed1993

Reporting radiotherapeutic complications in patients with uterine cervical cancer. The importance of latency and classification system.

Radiotherapeutic morbidity is reported according to our own system (AADK) and the Franco-Italian glossary (FI) in 442 patients with cervical cancer FIGO stage IIB (139), IIIA (10), IIIB (221), and IVA (72). The AADK system records each symptom, date of appearance, the required therapy, and its initial date. FI describes the maximal damage in 4 grades. Actuarial estimates of moderate or worse complications in the rectosigmoideum differed significantly in relation to stage, while frequencies did not differ. Frequencies were up to 25% lower than the actuarial estimates. Moderate AADK complications in the rectosigmoideum occurred from 1 to more than 24 months in 42% of stage IIIB patients finally developing severe FI complications, and during more than 2 years in 24% of the patients dying from rectosigmoid complications. An analysis of the probability of being alive without moderate or worse AADK complications indicated that survival and complications were unrelated. It is concluded that, with any classification system for reporting morbidity, each symptom and required therapy used in the definition of each complication grade and the date of appearance should be registered regularly to allow (1) reporting of the real risk of organ damage, (2) rescoring of complication grades, (3) separation of early and late morbidity, and (4) reporting of actuarial estimates. If these minimum requirements are met, underestimation of morbidity is avoided.

Adult↗
PubMed1993

Nicotinamide pharmacokinetics in humans and mice: a comparative assessment and the implications for radiotherapy.

Healthy human volunteers orally ingested escalating doses of up to 6 g nicotinamide in capsule form on an empty stomach. Some side-effects were seen although these were mild and transient. HPLC analysis of blood samples showed peak plasma levels, typically within 45 min after ingestion, which were linearly dependent on dose ingested. The elimination half-life and AUC were also found to increase with drug dose, although these increases were non-linear. Pharmacokinetic studies were also performed in female CDF1 mice with C3H mammary carcinomas grown in the right rear foot. Analysis of blood and tumour samples taken from mice injected i.p. with nicotinamide doses between 100-1000 mg/kg showed similar characteristics as the human data, although the elimination half-lives were not dose-dependent. The average peak plasma concentration of 160 micrograms/ml measured in humans after taking 6 g of nicotinamide was equivalent to that seen in mice after injecting 171 mg/kg. Using a regrowth delay assay the enhancement of radiation damage by nicotinamide in this mouse tumour was found to be independent of drug dose from 100-1000 mg/kg, resulting in a constant 1.3-fold increase in radiation response. Doses of nicotinamide that can be tolerated clinically should therefore produce adequate enhancements of radiation damage in human tumours.

Adult↗
PubMed1993

The effect of sequence and time interval between cyclophosphamide and total body irradiation on lung and bone marrow damage following bone marrow transplantation in mice.

The compromise between bone marrow killing effect and toxicity (mainly on the lungs) of the conditioning protocol used prior to bone marrow transplantation (BMT) determine to a great extent the final outcome. In search of an optimal balance between minimum lung damage and maximum bone marrow cell kill, we have tested the effect of varying the sequence and time interval between cyclophosphamide (CTX) and total body irradiation (TBI). CTX was administered almost concomitantly with TBI (i.e., 15 min before TBI) or 1-7 days before or after TBI. Lung damage was assessed by the lethality (LD) of the mice between day 28 and day 180 after treatment, bone marrow damage by the LD of the mice between day 7 and day 28 after treatment and by the spleen colony assay. Mice chosen for lung damage testing were rescued from death due to bone marrow ablation by transplantation with syngeneic marrow cells. CTX potentiated radiation damage in both bone marrow and lungs. The effect on the bone marrow was greater when CTX was given after TBI than when given before TBI and this effect was significantly more than additive when the interval between the two agents was 3 days. Lung toxicity, on the other hand, was greater when CTX was given before TBI than when given after TBI. A therapeutic gain factor (TGF) was estimated by dividing the dose enhancement ratio (DEF) of bone marrow damage over the DEF of lung damage at all the time intervals studied. The results were consistently higher when CTX was given after TBI than when given before.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Clinical correlations between late normal tissue endpoints after radiotherapy: implications for predictive assays of radiosensitivity.

The discovery that certain genetic syndromes are associated with a high cellular radiosensitivity has stirred interest in the concept that radiosensitivity of persons in general should have a genetic component. This has motivated research into assays for prediction of cellular normal tissue radiosensitivity. If such an intrinsic factor were a major factor in the development of late normal tissue injury, this should be detectable as a correlation between the probability of developing injury in different tissues. This hypothesis is tested in a series of 229 patients treated with postmastectomy radiotherapy and evaluated with respect to a number of late endpoints 16 to 71 months after the end of treatment. In each patient, the presence of marked subcutaneous fibrosis and telangiectasia were evaluated in two different treatment areas: in a photon field underneath a 5-mm wax bolus and in an abutted electron field used for treating the chest wall. The use of two different doses per fraction and the fact that a single anterior photon field was used with the dose prescribed at the level of the mid-axilla, led to a substantial variation in total dose and dose per fraction in these patients. A non-tissue-specific patient-to-patient difference in radiosensitivity would cause higher than expected reactions in one treatment area to be correlated with higher than expected reactions in the other area. For each of the two endpoints, telangiectasia or subcutaneous fibrosis, patients experiencing stronger than expected reactions in one treatment area tended to do so in the other area as well. Thus, a strong host factor appears to exist for a specific endpoint. It is an open question whether this is explained by individual variability in intrinsic radiosensitivity, progression rate of injury or other. Contrary to this, no significant correlation was seen when pairing the two late end-points, fibrosis and telangiectasia. Thus, patients showing stronger than expected fibrosis developed on average marked telangiectasia with a probability well predicted from their total dose and dose per fraction. These findings suggest that an assay for clinical expression of late injury would have to be specific for that type of injury.

Breast Neoplasms↗
PubMed1993

Histological grade, DNA ploidy and mean nuclear volume as prognostic factors in prostatic cancer.

Seventy-nine consecutive patients with prostatic cancer diagnosed between 1979 and 1983 were classified with respect to histological grade according to Shelley et al. (23), DNA ploidy (diploid, tetraploid and aneuploid), and mean nuclear volume (mnv) of the cancer cells. Nine patients were still alive at the time of analysis (minimum observation time 7.5 years). Univariate analysis showed that histological grade (p = 0.004), DNA ploidy (p = 0.0002) and mnv (p = 0.009) all had a significant influence on crude survival. A Cox proportional hazards model was used to analyse the prognostic value of these factors and patient age. However, when the two strongest of these four factors, histological grade (p = 0.0025) and DNA ploidy (p = 0.0035), were corrected for, age (p = 0.07) and mnv (p = 0.22) had no independent impact on crude survival.

Age Factors↗
PubMed1993

Reduction of cisplatinum-induced renal toxicity in mice by tetrahydroindazolonecarboxylic acid (HIDA) [corrected].

The ability of tetrahydroindazolone carboxylic acid (HIDA) to reduce the toxicity of cis-diamminedichloroplatinum (cis-DDP) in CDF1 mice was investigated. Toxicity was assessed both in terms of mouse lethality occurring within 14 days after treatment and kidney damage estimated by measurement of plasma urea. The levels of plasma urea were found to increase from day 2 after intraperitoneal (i.p.) injection of cis-DDP, reaching a peak at day 5. This increase was also cis-DDP-dose dependent. An i.p. injection of HIDA reduced kidney damage only when given 2.5 h prior to cis-DDP and at HIDA doses of 100 mg/kg or larger. The protection ratio for this reduction was 1.10. HIDA also decreased mouse lethality from cis-DDP, resulting in a PR of 1.41. This protective effect of HIDA on cis-DDP toxicity may eventually have a clinical application.

Animals↗
PubMed1993

A randomized feasibility study evaluating the effect of radiotherapy alone or combined with 5-fluorouracil in the treatment of locally recurrent or inoperable colorectal carcinoma.

The effect of radiotherapy alone or given simultaneously with 5-FU in the treatment of locally recurrent or inoperable colorectal carcinoma was investigated in a randomized feasibility trial. Twenty-nine patients were randomized to radiotherapy alone (50 Gy/5 weeks + 10-20 Gy boost), and 30 patients to the same radiotherapy with weekly 5-FU (600 mg/m2) given before treatment every Monday during the first 5 weeks. The two groups were comparable with regard to age, sex, previous treatment, symptoms, tumour size and performance status. Treatment compliance to radiotherapy was the same in both groups with 87% receiving at least 50 Gy. Drug treatment was completed in 18/30 patients. Overall the treatment resulted in a significant palliative effect in 73% of evaluable patients with a median duration of 26 months, and objective response in 32% (8 CR, 11 PR), with a median duration of 18 months. The 3-year actuarial survival rate was 9% (median 12 months). Only patients who achieved CR became long-time survivors (63% 3-year actuarial survival). Similarly, performance status had a strong association with survival. Multivariate analysis showed complete response and high performance status to be the only parameters having prognostic influence on survival. Addition of 5-FU did neither influence the objective or symptomatic response, nor the development of distant metastases. However, addition of the drug resulted in an apparent increase in the frequency of severe acute radiation complications (33% vs. 13% after irradiation alone).

Adult↗
PubMed1992

Auditory brain stem responses in patients after radiation therapy for nasopharyngeal carcinoma.

BACKGROUND: The study evaluated the incidence and severity of brain stem myelopathy occurring after radiation exposure in a cohort of patients who received external radiation exposure for nasopharyngeal carcinoma (NPC). METHODS: Brain stem function was investigated by auditory brain stem responses (ABR). RESULTS: Four of 21 patients who could be examined had aberrations in ABR. Three patients showed highly abnormal ABR, with no distinctive patterns or peaks. Two of these patients also showed clinical symptoms of brain stem dysfunction, including multiple palsies in cranial and peripheral nerves, whereas the third patient had no clinical signs of brain stem disorders. The fourth patient had minor conduction delays in ABR. The remaining group of 17 patients who could be examined had ABR latency and transmission times similar to those of the control group. None of these patients had neurologic symptoms. Dose-response analysis showed that patients who received radiation doses of 59 Gy or less to the brain stem had normal ABR, whereas four of six patients who received a dose of 68 Gy had manifest or subclinical brain stem dysfunction. CONCLUSIONS: The results emphasize the importance of protecting the brain stem from high-dose radiation when possible. The results also demonstrate the usefulness of ABR as a supplement to the clinical examination of patients with possible myelopathy occurring after radiation exposure.

Adult↗
PubMed1992

Stereologic, histopathologic, flow cytometric, and clinical parameters in the prognostic evaluation of 74 patients with intraoral squamous cell carcinomas.

BACKGROUND AND METHODS: A consecutive series of all 78 incident cases of intraoral squamous cell carcinoma occurring during a 2-year period in a population of 1.4 million inhabitants were evaluated by histologic score (the modified classification of Jacobsson et al.), flow cytometry, stereology, tumor size, and the TNM classification. RESULTS: The investigation showed a significant difference between the volume-weighted mean nuclear volume (nuclear vv) of oral leukoplakia (n = 29) and oral squamous cell carcinomas (P = 0.001). The value of the parameters as prognostic indicators of survival and recurrence was tested with Kaplan-Meier plots and Cox multiple hazard regression analysis. Tumor size, T-stage, stereologically estimated nuclear vv, and mean nuclear profile area were all of significant prognostic value in single factor analysis with reference to both survival and recurrence. The histologic parameters of mitotic activity, morphologic nuclear dedifferentiation, and histologic mean malignancy score and the DNA ploidy level had no prognostic value. A prognostic index based on the results of the Cox analysis that included T-stage and nuclear vv was correlated highly with survival (P = 0.00001) and recurrence (P = 0.002). CONCLUSION: These findings may contribute to optimal and individualized therapy.

Adult↗
PubMed1992

Effect of etoposide, carmustine, vincristine, 5-fluorouracil, or methotrexate on radiobiologically oxic and hypoxic cells in a C3H mouse mammary carcinoma in situ.

The effect of etoposide (VP16), carmustine (BCNU), vincristine (VCR), methotrexate (MTX), and 5-fluorouracil (5-FU) on the oxic and hypoxic cells in a C3H mammary carcinoma in CDF1 mice was investigated using an in situ local-tumor-control (TCD50) assay. The surviving fraction (SF) was calculated from the size of the radiation dose needed to inactivate the surviving tumor cells in drug-treated tumors relative to untreated controls. Preferential drug cytotoxicity towards oxic and hypoxic cells was evaluated from the difference in the response to irradiation under ambient and clamped conditions, respectively. Three drugs caused a significant (P less than 0.05) reduction in the survival of hypoxic cells, the SFs being 0.31 (VP-16), 0.13 (BCNU) and 0.16 (VCR). VCR was also toxic towards oxic cells (SF, 0.17), whereas VP16 and BCNU had no significant effect on these cells (SF, 0.5 and 0.76, respectively). Two drugs produced significant killing of cells in the oxic compartment: 5-FU (SF, 0.10) and MTX (SF, 0.22); these two drugs had no effect on hypoxic cells (SF, 0.78 and 1.11, respectively).

Animals↗
PubMed1992

BW12C-induced changes in haemoglobin-oxygen affinity in mice and its influence on the radiation response of a C3H mouse mammary carcinoma.

The effect of the substituted benzaldehyde BW12C on haemoglobin-oxygen binding affinity, tumour radiation response and blood perfusion were investigated in a C3H mouse mammary carcinoma grown in the feet of CDF1 mice. Mouse P50 (partial pressure of oxygen at half saturation) was estimated using an ABL blood gas analyzer; radiation response determined from tumour regrowth and local tumour control assays; and tumour blood perfusion measured with a 86RbCl extraction procedure. A single intravenous injection of BW12C substantially decreased mouse P50. This effect was dependent on the time after injection with the nadir observed within 15 min and only returning to normal after several hours. It was also dependent on drug dose, the decrease becoming larger with increasing concentration, reaching a maximum 50% reduction at 70 mg/kg. The decrease in P50 could be maintained for at least 6 h following injection of 70 mg/kg, if mice were also given 25 mg/kg at hourly intervals. However, no changes in radiation response or tumour blood perfusion were observed with either single or multiple administrations of BW12C. These results suggest that BW12C induced changes in tumour hypoxia reported by several groups of workers, may not be entirely the result of a change in haemoglobin-oxygen affinity.

Animals↗
PubMed1992

Fractionation sensitivity and latency of late radiation injury to the mouse urinary bladder.

Transurethral bladder filling is a functional, non-invasive, in vivo assay of early and late radiation injury to the mouse bladder. Fractionated irradiations using single doses or 2, 3, 5, or 10 dose fractions in an overall time of 4 or 4.5 days, with a range of total doses, were given to the bladder of 12-14 week-old C3D2F1/Bom mice. In 372 mice, bladder volume at an intravesical pressure of 20 mmHg was measured before irradiation and at regular intervals thereafter. The endpoint for late bladder injury was a volume of less than 50% of the median pretreatment volume in all animals, occurring more than 30 days after irradiation. This endpoint was reached after a latent period ranging between 35 and 401 days. Fractionation and latency parameters were estimated using a mixture model. There was a highly statistically significant dose-dependency of the latent period (p < 10(-8)). The alpha/beta ratio was estimated at 5.8 Gy [95% confidence limits (3.6; 8.8) Gy] for 250 kVp X-rays. Thus late radiation injury in the mouse urinary bladder is one of the least sensitive late endpoints with respect to change in dose per fraction. Introducing early bladder injury as a variable in the model improved the fit significantly (p = 0.03), but the alpha/beta ratio remained unchanged. Thus the hypothesis that late bladder injury may be, at least in part, consequent upon early injury did not explain the relatively high alpha/beta ratio for this late endpoint.

Animals↗
PubMed1992

Education in radiation oncology in Europe.

The outcome of an inventory among 22 European countries with respect to the radiotherapy facilities and the training of new radiation oncologists in each country is described. The radiotherapeutic profession, which mostly prescribes also cytostatics or hormones, has become well-regulated in the last 20 years. Most radiation oncologists are also involved in the diagnostic work-up and follow-up of the cancer patient. The numbers of radiotherapists and other staff, treatment capacities, and patients are given. The training for radiation oncologists is mostly taken at the university centers, but the curricula are rather diverse.

Europe↗
PubMed1992

Effect of carboxyhemoglobin on tumor oxygen unloading capacity in patients with squamous cell carcinoma of the head and neck.

Hemoglobin and blood gas parameters, with special attention to the influence of carboxyhemoglobin, were studied in 115 head and neck cancer patients undergoing radiotherapy. In 712 weekly blood samples, the values of total hemoglobin, carboxyhemoglobin (CO-Hb), and p50 were measured and the total oxygen content in the arterial and tumor venous blood was estimated. The difference between these values express the tumor oxygen unloading capacity (t-OUC). CO-Hb ranged from 0-12% and showed a significant inverse relationship with t-OUC. This was caused by a reduced amount of effective hemoglobin combined with a left shift of the oxyhemoglobin dissociation curve (reduced p50). Overall, the tumor oxygen utilization decreased from 70% to 52% as a function of an increase in CO-Hb from 0 to 12%.

Adult↗
PubMed1992

Improving the radiation response in a C3H mouse mammary carcinoma by normobaric oxygen or carbogen breathing.

The limited therapeutic benefit from nitroimidazoles has renewed the interest in normobaric oxygen as a hypoxic cell radiosensitizer. In this experimental study we have tried to modify the oxygenation of a C3H mammary carcinoma by flushing tumor-bearing mice with oxygen or carbogen for 5 min before and during treatment. The response to these treatments was evaluated by the changes in radiation-induced tumor control (TCD50) and by the changes in tumor hypoxic fraction (HF). Irradiation was given either as a large, single dose or as five equal, daily fractions. High levels of oxygen in the inspired air were found to decrease the TCD50 significantly. The enhancement ratios were in the range of 1.2-1.4 (p less than 0.05) for both single dose and fractionated irradiation, which suggests that hypoxic cells may be important even when reoxygenation is believed to be complete between fractions. The change in TCD50 corresponded to a decrease in the fraction of clonogenic hypoxic cells from 12% to 3-4% (p less than 0.05). Tumor blood flow was not significantly influenced by the gas treatment. This study thus shows that normobaric oxygen/carbogen inhalation may significantly improve the local tumor control by reducing the diffusion related hypoxia within tumors.

Administration, Inhalation↗