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Biomedical subjects

M Overgaard

Publications and source records attributed to M Overgaard.

At least 55 records · Page 3Linked to original sources
PubMed1992

Danish randomized trial comparing breast conservation therapy with mastectomy: six years of life-table analysis. Danish Breast Cancer Cooperative Group.

The Danish Breast Cancer Cooperative Group (DBCG) conducted a randomized trial comparing breast conservation with mastectomy in patients with invasive mammary carcinoma. From January 1983 to March 1989, the trial accrued a total of 1153 women. Of this number, 905 patients (79%) were randomly assigned to one of the two treatment options, whereas 248 patients (21%) did not accept randomization. Of the randomly assigned patients, 90% received the surgical option to which they had been originally assigned. In the breast conservation arm the tumor was excised with the intention of obtaining free margins determined at gross examination, and radiotherapy was subsequently administered to residual breast tissue. The axilla was dissected in all instances. Patient and tumor characteristics were similar in the two randomization arms. The median follow-up time was 40 months. At 6 years of life-table analysis the probability of recurrence-free survival was 70% in the breast conservation arm against 66% in the mastectomy arm. Survival figures were 79% against 82%, respectively.

Breast Neoplasms↗
PubMed1991

[Rationalization profits of radiographic diagnosis with systematic follow-up DBCG (Danish Breast Cancer Cooperative Group) programs. 1].

In the follow-up programme of the DBCG-77 control and treatment protocols for primary operable breast cancer, bone scintigraphy and chest X-ray were performed 6 months after surgery and thereafter yearly until the diagnosis of any recurrence or another cancer. In the present study, the value of the two examinations was examined to the 6th year control. As a result of a low incidence of primary recurrence to the bone (0.6-3.9%) and to the chest (0.0-3.0%) the value was found to be low. About two thirds of the patients with primary chest recurrence addressed themselves with or had at the time of control pulmonary symptoms. About one half of those patients, in whom (during a 12-month period after the scheduled bone scintigraphy) bone metastases were diagnosed by another method, had a normal scheduled bone scintigraphy. False positive changes were not infrequent, especially at the bone scintigraphies. The diagnosis of asymptomatic chest recurrence did not reduce the mortality among stage II patients, among whom the greatest value of the control examination was found. It is concluded, that systematic use of bone scintigraphy and chest X-ray is not justified in a follow-up programme for stage I and II breast cancer patients.

Bone and Bones↗
PubMed1991

[Prognosis after surgical treatment of breast cancer. 3. The low-risk group of the DBCG (Danish Breast Cancer Cooperative Group)].

The two therapeutic protocols of The Danish Breast Cancer Cooperative Group (DBCG) DBCG 77a (1977-1982) and 82a (1982-1990) comprise patients who were classified as low risk patients after operation for cancer of the breast, a total of 7,315 women. Treatment consisted of mastectomy and dissection of the lower and middle axillary levels. The median period of observation for DBCG 77a was 9 1/2 years and for DBCG 82a 3 1/3 years. The curves for recurrence-free survival and survival were found to be congruent in the two protocols. The recurrence-free survival after five years was 70% and 55% after ten years. Survival was 87% after five years and 70% after ten years. Local recurrence developed in 12.7% and 1.1% had distant recurrences simultaneously. Local recurrence was distributed with 60% in the scar or thoracic wall, 33% in the axilla and 7% in the clavicular lymph nodes. Distant recurrence alone developed in 11.4%. The time curves for development of local or distant recurrences were practically congruent. Local recurrence developed in 3.8% of the patients per annum during the first four years and after that in 1.5% per annum. Distant recurrence was found in 3.5% per annum in the first four years and after that in 1.8% per annum. The survival was significantly different after local and distant recurrence. Patients with tumours of grade 1 anaplasia had better prognoses than patient with grade 2 og 3 tumours as regards recurrence-free survival and survival. Multivariate analysis revealed that age under 40 years and anaplasia grad were significant prognostic variables for the parameters: distant recurrence and local recurrence. In addition, the number of lymph nodes in the operation specimen was a prognostic variable for local recurrence.

Adult↗
PubMed1991

[Adjuvant endocrine treatment of postmenopausal patients with breast cancer with high risk of recurrence. 5. Results from the DBCG (Danish Breast Cancer Cooperative Group) 77C randomized trial].

The role of antiestrogen treatment of postmenopausal breast cancer patients with high risk of recurrent disease is evaluated in a nationwide, prospective trial conducted by the Danish Breast Cancer Cooperative Group (DBCG). After total mastectomy and postoperative radiotherapy (RT), 840 patients were randomized to treatment with tamoxifen (RT + TAM) for one year, and 824 were randomized to no further therapy (RT). The recurrenceree survival (RFS) after ten years of lifeable analysis is 31% in the RT + TAM treated group, and 28% in the RT group (p = 0.01). Survival is 38% and 34% in the two treatment groups, respectively (p = 0.04). The data were further analyzed with respect to prognostic factors such as age, number of positive nodes, tumour size, and degree of anaplasia. Survival is prolonged in nearly all subgroups of patients treated with RT + TAM. However, the prolongation is only significant in patients with four or more positive nodes, with tumours of less than 5 centimeters or with tumours of anaplasia grade II. Estrogen (ER) and progesterone receptor (PgR) concentrations were measured in tumours from 309 and 219 patients, respectively. Only patients with ER and PgR values above 100 fmol/mg cytosol protein seemed to have a prolongation of survival. In conclusion, a modest survival benefit is achieved with one year of adjuvant tamoxifen treatment. Nevertheless, this is the first example of a systemic treatment approach being able to change the fatal course of breast cancer in postmenopausal patients. By means of endocrine therapy, and in the context of a new randomized trial, the DBCG will try to improve the survival in these patients even further.

Aged↗
PubMed1991

[Adjuvant chemotherapy in premenopausal and menopausal high-risk patients with breast cancer. 4. Results of the DBCG (Danish Breast Cancer Cooperative Group) 77B study].

From October 1977 to November 1982 premenopausal and menopausal high-risk breast cancer patients were included in a randomized trial (DBCG 77B). The primary surgical treatment was total mastectomy with axillary dissection. In the trial, a total of 1,034 patients were enrolled and received postoperative radiotherapy (RT) and were further randomized to 1) no systemic treatment, 2) cyclophosphamide, or 3) cyclophosphamide + methotrexate + 5-fluorouracil. The chemotherapy was given for one year. With a median observation time of ten years, the survival was 45, 60 and 62%, respectively. Retrospectively, the survival benefit was observed to be most pronounced in the age group less than 40 years, in patients with tumour size less than or equal to 5 cm or with less than or equal to 3 positive lymph nodes. In high-risk premenopausal and menopausal patients adjuvant chemotherapy combined with RT thus resulted in a more than 25% relative reduction in mortality at ten years of observation compared with RT alone.

Adult↗
PubMed1991

Relationship between early and late normal-tissue injury after postmastectomy radiotherapy.

Factors of importance in the development of telangiectasia were investigated in a series of 229 patients who, between 1978 and 1982, received postmastectomy radiotherapy with two different fractionation schedules. Patients who developed moist desquamation had a statistically significantly increased risk of developing telangiectasia after a specific course of radiotherapy. As an example the estimated incidence of severe telangiectasia after 44 Gy in 22 fractions increases from 27% to 49% in patients who developed grade greater than or equal to 2 moist desquamation as an early radiation reaction. A reanalysis of the Aarhus data with telangiectasia as the endpoint gave an alpha/beta ratio at 2.8 Gy (95% c.l. (-0.1, 8.1) Gy) and a relative biological effectiveness (RBE) of high energy electrons relative to 8 MV photons at 0.89 (95% c.l. (0.85, 0.93)). Patients age or the occurrence of severe erythema did not predispose to telangiectasia. A similar predisposition after moist desquamation was not seen for subcutaneous fibrosis. The RBE of high energy electrons relative to 8 MV photons for this endpoint was estimated at 0.88 (95% c.l. (0.86, 0.91].

Breast Neoplasms↗
PubMed1991

Nimorazole as a hypoxic radiosensitizer in the treatment of supraglottic larynx and pharynx carcinoma. First report from the Danish Head and Neck Cancer Study (DAHANCA) protocol 5-85.

Between January 1986 and September 1990, 442 patients with pharynx and supraglottic larynx carcinoma were randomized to receive the hypoxic cell radiosensitizer nimorazole (NIM) or placebo in association with a course of conventional primary radiotherapy. A preliminary analysis including the first 288 patients showed that the stratification parameters were significant (3-year actuarial local-regional tumor control, p less than 0.05) for sex (females 52% vs males 34%), tumor size (T1-T2 47% vs T3-T4 32%) and pre-irradiation hemoglobin (Hb) concentration (high 41% vs low 34%). Overall, the NIM group showed a significantly better local-regional control rate than the placebo group (46% vs 32%). There was an apparent additive effect of Hb concentration and NIM. Thus, in the male group, placebo patients with low Hb had a 23% control rate compared to 46% in NIM treated patients with Hb above 9 mmol/l (p less than 0.05). The similar effect in females could not be evaluated due to the small number of women with this disease. NIM was well tolerated and drug-related side effects were minor and tolerable, with transient nausea and vomiting as the most frequent complication. A final conclusion of the study must await an evaluation including all patients and a longer observation time.

Carcinoma↗
PubMed1991

Sensori-neural hearing loss in patients treated with irradiation for nasopharyngeal carcinoma.

The present investigation has been carried out to evaluate the sensitivity of the inner ear to irradiation. Cochlear function was tested in a cohort of 22 patients before and 7-84 months after receiving external irradiation for nasopharyngeal carcinoma. The pre-irradiation sensori-neural hearing threshold at 500, 1000, 2000, and 4000 Hz was used as a baseline for the individual patient, and the observed sensori-neural hearing loss (SNHL) was calculated as the difference between pre- and post-irradiation values. The pre-irradiation hearing level or patient age was not correlated with the actual SNHL. In contrast, there was a significant correlation between the total radiation dose to the inner ear and the observed hearing impairment. SNHL was most pronounced in the high frequencies, with values up to 35 dB (4000 Hz) and 25 dB (2000 Hz) in some patients. The latent period for the complication appeared to be 12 months or more. The deleterious effect of irradiation on the hearing should be kept in mind both in treatment planning and in the follow-up after radiotherapy.

Adult↗
PubMed1990

Time-dose factors in radiotherapy: a review of the human data.

The values for alpha/beta (fractionation sensitivity, or recovery capacity) for early and late reactions in human normal tissues are consistent with results from experimental animals. For breast treatments direct analysis indicates that for early reactions alpha/beta is in the range 7 to 11 Gy, while for late effects it is in the range 2 to 4 Gy. Data on recovery kinetics in human tissues is limited but these indicate that recovery may be slower in humans than in rodents. For early skin reactions the halftime of recovery is about 1 h, while for late telangiectasia it is more than 3 h. alpha/beta values for human tumors are more variable than in rodents: some are high (head and neck, lung, skin, cervix) and similar to those for early reacting normal tissues. Others are low, including melanomas, where alpha/beta was estimated at 0.6 (-1.1, 2.5) Gy, and liposarcomas, where direct analysis of cases surveyed from the literature suggested that alpha/beta = 0.4 (-1.4, 5.4) Gy. Repopulation kinetics is faster in the mucosa of the soft palate and faucial pillars (1.8 Gy/day) than in head and neck tumors (up to 1 Gy/day).

Animals↗
PubMed1990

Evaluation of radiotherapy in high-risk breast cancer patients: report from the Danish Breast Cancer Cooperative Group (DBCG 82) Trial.

The role of postmastectomy irradiation together with systemic treatment was evaluated in high-risk patients included in the Danish Breast Cancer Cooperative Group (DBCG) protocol 82. As of June 1989, a total of 1473 pre- and menopausal patients were randomized to postmastectomy irradiation + CMF versus CMF alone (protocol 82-b). A total of 1202 postmenopausal patients were randomized to postmastectomy irradiation + Tamoxifen versus Tamoxifen alone (protocol 82-c). At 5 years the actuarial loco-regional recurrence rate was significantly lower in the irradiated patients (82-b: 9% vs 28%, 82-c: 6% vs 36%). Further, disease-free survival was significantly improved in both pre- and postmenopausal irradiated patients compared with those who had only systemic treatment (82-b: 54% vs 47%, 82-c: 52% vs 38%). At present, overall survival is significantly different in 82-b patients (68% vs 63%) but not in post-menopausal 82-c patients (62% vs 61%). Thus, adjuvant systemic treatment alone (chemotherapy or tamoxifen) did not prevent loco-regional recurrences in high-risk patients after mastectomy and axillary lymph node sampling. However, a longer observation time is necessary to evaluate the consequence of primary optimal loco-regional tumor control in high-risk breast cancer patients with respect to overall survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Squamous cell carcinoma of the oropharynx: an analysis of 213 consecutive patients scheduled for primary radiotherapy.

Radiotherapy was administered to 213 consecutively treated patients with oropharyngeal squamous cell carcinoma. The classification (Union Internationale Contre le Cancer, 1982) showed primary tumors (T1, 13%; T2, 51%; T3, 34%; T4, 2%) and regional lymph nodes (N0, 38%; N1, 38%; N2, 4%; N3, 20%). The 10-year actuarial value for local control was 48%; for regional control, it was 66%. Distant failure occurred in 20 patients. The 10-year actuarially corrected survival rate was 40% (stage I, 57%; stage II, 51%; stage III, 43%; stage VI, 21%). Locoregional tumor control was significantly influenced by irradiation parameters (total dose and treatment time), tumor volume, sex, and hemoglobin value. It is concluded that local control of the tumor while still in the T position is the parameter most crucial to success. This end point is currently being aimed at evaluating primary surgery and testing a radiation technique with larger total doses and shrinking fields and a new radiosensitizer, while at the same time investigating the influence of hemoglobin concentration.

Adult↗
PubMed1989

Clinical radiobiology of malignant melanoma.

Tumor-control probability (TCP) was analyzed in a series of 121 patients having 239 histologically proven recurrent or metastatic malignant melanomas. These were treated with fractionated radiotherapy with various doses per fraction, total doses, and overall times. Cutaneous lesions (127, 53%) were treated with electron beams, and more deeply seated tumors (112, 47%) with 60Co or 4-8 MV X-rays. The fraction size was highly variable, and this permitted determination of the alpha/beta ratio in the multifraction linear-quadratic model, which was estimated at 0.57 Gy with 95% confidence limits [-1.07, 2.5] Gy. Treatment time had no demonstrable influence on TCP. Thus this tumor exhibits the fractionation sensitivity characteristic of a late-responding normal tissue, suggesting that an adequate fractionation schedule for malignant melanomas would be characterized by larger-than-conventional doses per fraction, possibly about 6 Gy per fraction. This is consistent with the conclusions of other authors. Tumor size, evaluated as mean tumor diameter, S, had a major impact on TCP: the number of target cells increased as a power function of S with exponent 0.72 (95% confidence limits [0.49, 0.94]. In fact, a considerable amount of the heterogeneity in the dose-response data could be removed by accounting for size. Thus, the weak or absent dose response became highly significant. When a patient had multiple lesions, the responses of these to radiotherapy tended to be similar, thus implying that results were significantly influenced by a "hidden parameter" (such as inherent radiosensitivity or immunological status). A test of the predictive value of the TCP-model was performed in a different series of 183 cutaneous and lymph node malignant melanomas. The observed dose-response relationship in this data set was in good agreement with the model prediction. A chi-square test for goodness-of-fit showed that the variation between predicted and observed results could be explained by the binomial variation on quantal response data.

Cobalt Radioisotopes↗
PubMed1989

Latent-time estimation for late cutaneous and subcutaneous radiation reactions in a single-follow-up clinical study.

In this paper, an analysis of the fractionation sensitivity and latency of subcutaneous fibrosis and telangiectasia in a clinical series is presented. The series comprised 163 breast cancer patients who, from 1978 to 1980, received postmastectomy irradiation delivered in 12 fractions, with 2 fractions per week over a period of 37 to 46 days. The total dose was specified either as a maximum absorbed dose of 51.36 Gy, or as a minimum target dose of 36.6 Gy specified at the level of the mid-axilla. From 1981 to 1982, 66 patients received a minimum target dose of 40.92 Gy in 22 fractions administered as 5 fractions per week over 29 to 35 days. Late complications were evaluated prospectively at a single follow-up after a minimum observation time of 16 months. The clinical endpoints analyzed were subcutaneous fibrosis and telangiectasia. The data were analyzed using a mixture model that incorporates both dose fractionation and latency effects. The length of time to expression of 90% of the ultimate frequency of moderate or severe complications was 3.2 years (95% confidence limits (c.l.) [2.3,3.9] years) and 4.7 years (95% c.l. [4.0,4.8] years) for fibrosis and telangiectasia respectively, while the alpha/beta ratios were 1.9 Gy (95% c.l. [0.8,3.0] Gy) and 3.7 Gy (95% c.l. [0.2,47] Gy), respectively. For subcutaneous fibrosis the time to reach a specific grade of reaction increases with the grade, thus being consistent with the clinical impression that fibrosis progresses in severity over time. If latency and censoring effects are unaccounted for, serious underestimates of the ultimate frequency of radiation complications in groups with incomplete follow-up may result.

Breast Neoplasms↗
PubMed1989

Fractionation sensitivity of a functional endpoint: impaired shoulder movement after post-mastectomy radiotherapy.

A clinical radiobiological study of the fractionation sensitivity of impaired shoulder movement after postmastectomy radiotherapy is presented. From 1978 to 1980, 163 breast cancer patients received postmastectomy irradiation delivered in 12 fractions, 2 fractions per week, over a period of 37 to 46 days. The total dose was specified either as a maximum absorbed dose of 51.36 Gy, or as a minimum target dose of 36.6 Gy specified at the level of midaxilla. From 1981 to 1982, 66 patients received a minimum target dose of 40.92 Gy in 22 fractions with 5 fractions per week over a period of 29 to 35 days. The treatment technique remained essentially unchanged during the whole period of 1978 to 1982. Maximal flexion and abduction of the arm were measured with unfixed scapula. A relative score, indicating the grade of impaired shoulder movement on a nominal scale from 0-3, was established by comparison with the mobility of the contralateral arm. In addition, working ability and pain at movement and at rest were evaluated. These performance parameters significantly correlated with the grade of impaired shoulder movement. The occurrence of moderately or severely impaired shoulder movement was analyzed using a mixture model incorporating dose-fractionation, latency, and predisposing clinical factors. The risk of shoulder problems was significantly higher among patients above 60 years of age. The analysis pointed to subcutaneous fibrosis as a disposing factor and indicates that postoperative physical exercise programs are beneficial. Arm edema had no statistically significant influence on shoulder performance. The alpha/beta ratio was estimated at 3.5 Gy with 95% confidence limits (c.l.) [0.7, 6.2] Gy. The length of time to expression of 90% of the ultimate frequency of moderate and severe shoulder impairment was estimated at 3.9 years with 95% confidence limits [3.1, 4.6] years. The nominal standard dose (NSD) formalism failed to produce isoeffective total doses with respect to impaired shoulder movement in the two fractionation schedules. Although the deleterious effects of larger-than-conventional dose fractions have been documented in a number of clinical series, this study represents the first quantitation of the fractionation sensitivity of a functional clinical endpoint.

Adult↗
PubMed1989

Fractionation parameters for human tissues and tumors.

Time-dose factors such as fractionation sensitivity (alpha/beta) can sometimes be estimated from clinical data, when there is a wide variation in dose, fraction size, treatment time, etc. This report summarizes estimates of fractionation parameters derived from clinical results. Consistent with the animal data, alpha/beta is higher for acutely responding than for late-responding normal tissues. While many human tumors seem to be characterized by high alpha/beta values, there are exceptions (e.g. melanomas). Repair kinetics may be slower in human than in rodent skin and mucosa, but there are no hard and fast estimates of the repair halftime. Regeneration in head and neck tumors is equivalent to a daily dose of 1 Gy or less, while in the mucosa it is equivalent to approximately 1.8 Gy/day.

DNA Repair↗
PubMed1988

Some methodological problems in estimating radiobiological parameters from clinical data. Alpha/beta ratios and electron RBE for cutaneous reactions in patients treated with postmastectomy radiotherapy.

A number of biological, dosimetric, and statistical problems encountered in the determination of alpha/beta ratios and the relative biological efficiency (RBE) of high energy electrons are discussed. The analysis is based on isoeffect dose determination from logit analysis of dose-response data. Monte Carlo simulations of the logit analysis show that the estimated isoeffect dose may be treated as a normally distributed random variable. Under this assumption, formulae for the standard error of the derived radiobiological parameters are presented. The importance of specifying not only parameter estimates but also their confidence limits is emphasized. As a practical example, the dose-response relationships for severe erythema and subcutaneous fibrosis are discussed in two series of patients treated with postmastectomy irradiation with electrons and photons in two fractionation schedules. Because of a different dose per fraction in the electron and photon fields, a determination of RBE requires a fraction size correction. This is performed using the alpha/beta formalism. The present analysis suggests a high energy electron RBE for severe erythema of 0.93 (95% confidence limits 0.89 and 0.96) and for subcutaneous fibrosis of 0.84 (95% confidence limits 0.77 and 0.92).

Breast Neoplasms↗