PubMed Health⌕ Search

Biomedical subjects

J Overgaard

Publications and source records attributed to J Overgaard.

At least 145 records · Page 8Linked to original sources
PubMed1994

Quantitative magnetic resonance for assessment of radiation fibrosis after post-mastectomy radiotherapy.

Subcutaneous fibrosis is a serious complication of post-mastectomy radiotherapy with a pronounced influence on skin conditions, shoulder movement and arm oedema. To establish safer radiotherapy schedules, precise evaluation of the tissue damage is required. A feasibility study was performed to assess the value of calculated relaxation times from magnetic resonance (MR) images for quantitative characterization of different degrees of subcutaneous fibrosis after post-mastectomy radiotherapy. A surface coil was applied to the irradiated area, as well as to unirradiated skin, to obtain appropriate MR coronal slices for acquisition of calculated values using a mixed imaging sequence technique. 14 patients with clinically diagnosed subcutaneous fibrosis were examined, 10 of whom had severe fibrosis. The mean T2 values of the treated and untreated side were 53.0 and 56.7, respectively. A statistically significant decrease of the calculated T2 values on the treated side was observed. No correlation was found between the clinically assessed fibrosis and the calculated relaxation times. The findings indicate that despite a general decrease of T2 calculated values, the large variation in the relaxation times restricts the value of MR, as applied in this study, in differentiating between different degrees of fibrosis in normal tissues after radiotherapy.

Aged↗
PubMed1994

Continuous or split-course combined external and intracavitary radiotherapy of locally advanced carcinoma of the uterine cervix.

From 1974 to 1984, 442 consecutive patients with carcinoma of the uterine cervix (FIGO IIB: 139, IIIA:10, IIIB:221, IVA:72) were referred for combined intracavitary (IRT) and external radiotherapy (ERT). To improve local control and reduce late rectosigmoid morbidity the treatment strategy was changed from continuous (CRT) to split-course radiotherapy (SCRT) in 1978. Stage by stage the 5-year actuarial estimates of survival, local control, and late morbidity did not differ in relation to strategy. In the patients with tumours larger than 8 cm, the SCRT involved an increased dose in point B, a reduced dose in point A from the IRT, a lower total dose in point A, and a 34 days' prolongation of the total treatment time (TTT). The resulting 5-year actuarial local control rates were significantly lower compared with those after CRT. No difference of late severe morbidity was found except in IVA patients. In the patients with tumours between 4 and 8 cm, the SCRT involved a reduced dose in point A from the IRT, an increased total dose in point A and B, and a 50 days' prolongation of the TTT. In patients with stage IIB, the 5-year actuarial central local control rate was lower (p = 0.06), and the 5-year estimate of late severe morbidity significantly higher after SCRT compared with CRT. It is concluded that the increase of the dose in point B in the SCRT was insufficient to prevent the deleterious effect on local tumour control of either the lower dose from IRT in point A, or the prolonged TTT. The increase of the total dose in the SCRT may explain why the late morbidity was not reduced, and may suggest that the TTT is of no significant importance for the risk of late normal tissue damage.

Adult↗
PubMed1994

Reducing acute and chronic hypoxia in tumours by combining nicotinamide with carbogen breathing.

The ability of nicotinamide and carbogen breathing to improve the radiation response of a C3H mammary carcinoma by reducing both acute and chronic hypoxia was investigated. Using a tumour growth delay assay the response of 200 mm3 foot tumours to local irradiation was found to be increased by either injecting nicotinamide (100-1,000 mg/kg) 20 min prior to irradiation, or by allowing mice to breathe carbogen for 10 min before and during the radiation treatment. The greatest radiosensitization occurred when nicotinamide and carbogen were combined. With a histological fluorescent staining technique nicotinamide was shown to prevent transient stoppages in microregional blood flow, and also appeared to improve tumour oxygenation as measured with an Eppendorf oxygen electrode, both effects being consistent with its ability to decrease perfusion limited acute hypoxia. Carbogen had no effect on vessel closure, but it significantly improved tumour oxygenation, which was indicative of it reducing diffusion limited chronic hypoxia.

Animals↗
PubMed1994

Measurement of human tumour oxygenation status by a polarographic needle electrode. An analysis of inter- and intratumour heterogeneity.

Tumour oxygenation status was measured by a polarographic needle electrode in 31 patients with lymph node metastasis of squamous cell carcinoma of the head and neck and 18 patients with primary soft tissue sarcoma. Two oxygenation parameters, the median pO2 and the proportion of measured values less than 5 mm Hg, were used in comparing the inter- and intrasubject heterogeneity in tumour and subcutaneous tissue. Results of the analysis may be summarized as follows: 1) the variation in oxygenation between tumours was significantly greater than that within tumours, 2) the variation in oxygenation of subcutaneous tissue between patients was significantly greater than the variation within patients, 3) oxygenation of tumour was significantly lower than that of subcutaneous tissue, 4) no significant difference in the distribution of the oxygenation parameters in the two tumour types, and 5) both oxygenation parameters correlated. In conclusion, measurements by oxygen electrodes were able to distinguish intratumour heterogeneity from intertumour heterogeneity provided that several electrode tracks were done. The method therefore appears to be feasible for differentiation of tumour oxygenation clinically.

Adult↗
PubMed1994

Deep heating using a movable applicator phased array hyperthermia system. A preclinical feasibility study.

A preclinical evaluation of the 'movable applicator phased array hyperthermia system' was performed. The system employs four coherent applicators enabling power steering by amplitude and phase control. This concept has already been used in other systems, but the combination with a compact applicator design and easy movement of applicators has not been used before. The paper contains a description of the system and a verification of its performance using quality assurance tests with scanned E-field measurements. A clinical simulation was performed in pig to address the clinical feasibility of the system. The target volume was the left kidney. Two heating sessions, with and without occluded blood-flow to the kidney, were performed. In the low-flow experiments a temperature of 48 degrees C and 46 degrees C was obtained in the upper and lower pole of the kidney respectively. For the high-flow experiment the temperature in the upper pole was 48 degrees C.

Animals↗
PubMed1994

Clinical evaluation of nitroimidazoles as modifiers of hypoxia in solid tumors.

Hypoxic modification by nitroimidazoles has been explored in a large number of clinical studies. Nine different drugs (misonidazole, metronidazole, benznidazole, desmethylmisonidazole, etanidazole, pimonidazole, nimorazole, ornidazole, and RSU 1069) have reached clinical evaluation. Phase I and II trials have demonstrated a relationship between drug tolerance and expected hypoxic modification. Thus, the most tolerable drugs, viz., 5-nitroimidazoles, are those with the smallest preclinical activity. However, they may be the most clinically active, due to higher plasma and tumor concentrations. The clinical evaluation of hypoxic modification is difficult, since clinically important hypoxia can be observed only indirectly. There is, however, indirect evidence of substantial hypoxia in human tumors, although with considerable heterogeneity among individual tumors. More than 7000 patients have been included in 50 randomized trials. A meta-analysis showed that modification of tumor hypoxia significantly improved the loco-regional tumor control after radiotherapy with an odds ratio of 1.17 (95% confidence limits 1.06 to 1.28). The treatment benefit could mostly be related to an improved response in head and neck with odds ratio 1.23 (95% confidence limits 1.09 to 1.37), and to a lesser extent in bladder tumors; no significant effect was observed in other tumor sites (cervix, lung, central nervous system, and esophagus). Similarly to the local control benefit, the overall survival rate was improved with an overall odds ratio of 1.13 (95% confidence limits 1.03 to 1.23). The clinical trials showed no evidence of significant chemosensitization or direct bioreductive effect. Although 50 randomized clinical trials were evaluated, the median number of patients was only 97 (range 17-620). Clinical trials of this size are not likely to detect the observed differences, which may explain the lack of significant improvement in most of the individual studies. However, the overall results indicate that the biological issue related to hypoxia appears to be a sound rationale, especially with regard to head and neck and bladder carcinoma. Future studies related to the hypoxic problem should therefore preferably be aimed towards such tumors.

Antineoplastic Agents↗
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↗