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J Overgaard

Publications and source records attributed to J Overgaard.

At least 235 records · Page 13Linked to original sources
PubMed1988

Predictive value of flow cytometric DNA-analysis on fresh retinoblastoma tissue.

The cellular DNA content and the distribution of tumour cells in different phases of the cell cycles has been analysed in 8 consecutive enucleated eyes with retinoblastoma. All tumours had abnormal ploidy levels. The analysis did not reveal any specific pattern in 2 tumours which had metastasized compared to 6 local tumours. The flow cytometric analysis alone or in combination with histopathology appeared not to improve the classification of large retinoblastomas.

Child, Preschool↗
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↗
PubMed1988

Comparison of conventional and split-course radiotherapy as primary treatment in carcinoma of the larynx.

Based on our experience with conventional, daily irradiation, a split-course radiation schedule was introduced in 1978. The schedule, which was based on Cohen's models for squamous cell carcinoma and vascular damage respectively, predicted an improved tumour control and a reduced rate of late complications, e.g. late oedema, if the conventional, daily treatment was replaced by a split-course schedule. The schedule has later been abandoned, but the experience gained from split-course treatment at various dose levels has been analysed and the results compared with those obtained by conventional radiation. The data allowed construction of dose-response curves and estimation of iso-effect doses. Split-course treatment was associated with a significantly reduced therapeutic ratio because, disappointingly, it did not improve tumour control, and the severity of late complications grew. No late complications were avoided by introducing a 3-week pause in the radiation therapy regimen, nor was the tumour response improved despite a 12-Gy increase in total dose. This indicates a significant repopulation corresponding to more than 0.5 Gy/day, equivalent to an up to 100-fold increase of the number of clonogenic tumour cells during the pause--an increase that occurred despite the decrease, clinically, of the tumours during this period.

Carcinoma, Squamous Cell↗
PubMed1987

Experimental studies of photodynamic therapy in a retinoblastoma-like tumour.

Combination therapy with a purified hematoporphyrin derivative, Photofrin II, and red light (photodynamic therapy) was investigated in a retinoblastoma-like tumour growing in the eyes of rats in vivo and in cell cultures. There was a marked dose-response relationship between Photofrin II and the light energy both in vitro and in vivo. Up to 33% of the tumours could be controlled in vivo. In vivo/in vitro assays indicated Photofrin II uptake in the tumour cells in vivo in relation to the administered doses. Studies of cell death kinetics suggested that the mechanisms of photodynamic therapy were both a primary cell kill effect and a secondary tissue destruction, probably as a consequence of vascular damage.

Animals↗
PubMed1987

Orgotein in radiation treatment of bladder cancer. A report on allergic reactions and lack of radioprotective effect.

The possible protective effect of orgotein (a superoxide dismutase) on radiation cystitis and proctitis was studied in patients with carcinoma of the urinary bladder. A double-blind study in 60 patients was planned but due to unacceptable side effects only 30 patients were included. Radiation treatment was given with curative intent at a dose of 63 Gy in 30 fractions. Orgotein was injected 15 min after each daily radiation treatment at a dose of 4 or 8 mg. No effect of orgotein on tumour radiation response or on the acute radiation reactions in the bladder and rectum was detected. Marked subcutaneous infiltration and redness was seen at the local injection site in 5 patients. No general symptoms were observed. Intradermal tests and antibody titration tests showed that the local reactions were due to allergic reactions to the drug itself. The lack of radioprotective effect and the high frequency of unacceptable side effects makes orgotein an unsuitable drug in clinical radiation therapy.

Actuarial Analysis↗
PubMed1986

Postoperative radiotherapy in Dukes' B and C carcinoma of the rectum and rectosigmoid. A randomized multicenter study.

Results obtained during the first 5 years of a randomized study of postoperative radiotherapy (50 Gy) are presented. Criteria for randomization were fulfilled in 494 of 861 patients with Dukes' B and C tumors, when the trial was closed. Severe complications from radiotherapy approximated 10%. Probability of survival without local failure within 24 months was significantly higher after radiotherapy in patients with Dukes' C tumors, and the time of local failure was delayed 1 year. Patients with Dukes' B tumors had no benefit from radiotherapy. Risks of distant metastases and death were not influenced by radiotherapy in the main groups. Plasma-CEA measurements were evaluated blindly, and radiotherapy changed the critical levels of CEA for detection of recurrent cancer. It was concluded that patients with Dukes' C tumors may benefit from radiotherapy and plasma-CEA levels are influenced by radiotherapy, which may be important, when these are used in screening for recurrent cancer.

Actuarial Analysis↗
PubMed1986

Primary radiotherapy of larynx and pharynx carcinoma--an analysis of some factors influencing local control and survival.

An analysis of 950 patients with carcinoma of the larynx and pharynx was performed to identify factors of importance for local control and survival other than the TNM-classification. All patients were treated with primary radiotherapy, with doses ranging between 60-68 Gy in 6-7 weeks. The achievement of local-regional control by primary radiotherapy was highly correlated with disease-free survival (98% actuarial 5 year probability), which was significantly better than in patients who failed in the primary treatment but were salvaged by radical surgery. Furthermore, occurrence of distant metastases were almost all associated with failure to control the primary tumor. Sex was found to be a dominant prognostic factor, and in all sites and stages, women had a significantly better prognosis both with regard to local control and survival. The degree of histopathological differentiation was not significantly correlated with local control but with the incidence of distant metastases, which was significantly higher in patients with poorly differentiated tumors. In both males and females the pre-treatment hemoglobin concentration was correlated with the probability of primary tumor control and survival but only in patients with pharyngeal and to a lesser degree supraglottic tumors. In these groups, patients with hemoglobin levels above 13 g% (females) and 14.5 g% (males) had a significantly better prognosis than comparable patients with lower hemoglobin values. Such correlation could not be detected in patients with glottic tumors. The influence of tumor size was analyzed in a larger group of 1,060 patients with laryngeal carcinoma. In this group a notable correlation between tumor size and prognosis was observed within the various T-categories, indicating the tumor size as a significantly important parameter related to both probability of local control and survival. The study reveals that head and neck cancer is a heterogeneous disease and it is demonstrated that attention should be given to the various prognostic parameters since important therapeutic achievement is otherwise lost.

Carcinoma, Squamous Cell↗
PubMed1986

Interactions of radiation, cyclophosphamide and nimorazole in a C3H mammary carcinoma in vivo.

The combined effect of adjuvant Cyclophosphamide (CTX) and the hypoxic radiosensitizer, Nimorazole (NIM), on the radiation response was studied in a C3H mammary carcinoma in CDF1 mice. The effect of NIM and CTX alone or in combination without radiation was assessed by tumor growth delay measured by tumor growth time (TGT). Administration of CTX (100 mg/kg) increased the TGT from 5.2 days in untreated controls to 18.8 days. NIM (1000 mg/kg) had no effect on the TGT. The combined treatment with NIM given 4 hrs before CTX did not increase the TGT compared with CTX alone, which suggests that NIM does not potentiate CTX. The possible effect of an interaction between the therapeutic parameters was determined by administration of NIM, CTX, and radiation in different sequences to C3H mammary tumor bearing mice. The drugs were administered as single doses before or after graded single doses of irradiation. The end point was the radiation dose required to achieve local tumor control in 50% of the mice (TCD50). The enhancement ratio (ER)--defined as TCD50 for radiation alone relative to TCD50 for radiation combined with drug--was 1.2 for CTX given either 15 min before or 4 hrs after radiation. NIM given 30 min before radiation showed an ER of 1.6, but no enhancement was obtained when NIM was given after radiation. When NIM was given immediately after radiation, followed 4 hrs later by CTX, the ER was 1.2. However, applying NIM 30 min before radiation and CTX 3.5 hrs after radiation, the ER increased to 1.6. NIM given 30 min before, together with CTX given 15 min before radiation, showed an ER of 1.8. Our data suggest that: an improved tumor response may be expected when CTX is added to a radiation and hypoxic radiosensitizer treatment; this improvement is attributable to an additive effect based on the chemotherapy response alone rather than to chemopotentiation by the hypoxic radiosensitizer.

Animals↗
PubMed1986

The role of radiotherapy in recurrent and metastatic malignant melanoma: a clinical radiobiological study.

A review of the literature and our data has been completed to analyze the clinical radiobiology of malignant melanoma. Six hundred eighteen radiotherapy-treated malignant melanoma lesions were analyzed with regard to radiobiological parameters such as total dose, dose per fraction, treatment time, tumor volume, and various fractionation models. Forty-eight per cent of the treated tumors achieved complete response, which was persistent in 87% after 5 years. Neither total dose, treatment time, nor various modifications of the NSD concept showed any well-defined correlation with response. There was, however, a significant relationship between dose per fraction and response, and a high dose per fraction yielded a significantly better response (59% CR for doses greater than 4 Gy versus 33% CR for doses per fraction less than or equal to 4 Gy). The lack of treatment time influence allowed analysis of the data according to the linear-quadratic model, resulting in an alpha/beta ratio of 2.5 Gy. Using this ratio, an iso-effect for different fractionation schedules could be estimated by the extrapolated total-dose (ETD). The ratio was further improved when corrected for the tumor volume. Thus, an iso-effect formula for malignant melanoma could be calculated as: ETDvol (Gy) = D X [d + 2.5)/2.5) X M-.33, where D and d are total dose and dose per fraction in Gy, respectively, and M is the mean tumor diameter in cm. Based on a logit analysis, a complete response level of 50% appeared at an ETDvol value of 83 Gy. The formula is currently the best way to determine an optimal radiation schedule for an effective radiation treatment of malignant melanoma. The tumor response was further improved in 134 additional cases receiving adjuvant hyperthermia. Here, a thermal enhancement ratio (TER) of 2.0 was observed. In a group of 131 patients with only local or regional disease, a 5 year survival rate of 49% was observed in 77 patients with persistent local tumor control, but only 3% survived among the 54 patients in whom local therapy failed. It is therefore, highly important to the probability of survival in recurrent melanoma that proper local treatment be performed.

Follow-Up Studies↗
PubMed1986

Some factors of importance in the radiation treatment of malignant melanoma.

The results of radiotherapy in 204 lesions of malignant melanoma in 114 patients were analysed with regard to radiobiological parameters such as total dose, dose per fraction, treatment time, tumour volume and also by various fractionation models. Ninety-seven of 204 lesions showed a complete response (CR) which was persistent in 80. Neither total dose, treatment time nor various modifications of the nominal standard dose (NSD) concept showed any well-defined correlation with response. There was, however, a significant relationship between dose per fraction and response so that high doses per fraction yielded a significantly better response (24% CR for doses less than 4 Gy vs. 57% CR for doses greater than or equal to 4 Gy, p less than 0.001). The lack of influence of treatment time influence allowed an analysis of the data according to the linear-quadratic model yielding an alpha/beta ratio of 2.5 Gy. Using this ratio, an iso-effect for different fractionation schedules could be estimated by the extrapolated total dose (ETD). This was further improved when corrected for the other important parameter which was tumour volume. Thus, an iso-effect formular for malignant melanomas could be calculated as ETDvol = D X ((d + 2.5)/2.5) X M-0.33 where d is total dose and dose per fraction in Gy, respectively and M is mean diameter (cm). The 50% response for ETDvol was found to be 86 Gy. This formular seems to be currently the best way to determine an optimal radiation schedule for effective radiation treatment of malignant melanoma. Treatment of 45 patients with only local or regional disease showed 26 patients who achieved local tumour control with a 56% 3-year survival compared to no survivors among 19 patients in whom the disease could not be controlled locally. This indicated that proper attention should be given to the local treatment of recurrent melanoma since this has important implications for survival. Successful treatment of malignant melanoma may be possible when the special radiobiological features of the disease are taken into account.

Dose-Response Relationship, Radiation↗
PubMed1986

Effect of cancer chemotherapeutic drugs on radiation-induced lung damage in mice.

The effect of adriamycin (ADM), bleomycin (BLM), cyclophosphamide (CTX), 5-fluorouracil (5-FU), methotrexate (MTX), mitomycin C (MM-C) and cis-diamminedichloroplatinum(II) (cis-DDP) on the radiation-induced lung damage in mice was assessed by the ventilation rate (VR) and the lethality. Single drug doses were administered 15 min before graded single doses of irradiation and at different intervals from 28 days before to 28 days after fixed radiation doses. ADM, BLM and CTX administered 15 min before irradiation enhanced the radiation response with dose effect factors (DEF) of 1.46, 1.56 and 2.35, respectively. The effect of MM-C presented a complex picture. The drug had no effect at administration 15 min before 14-20 Gy, but enhanced the radiation response if given 15 min before 6-12 Gy (DEF = 1.57). The radiation-modifying effect of ADM, BLM, CTX and MM-C was most pronounced when the drugs were given 15 min before irradiation. The effect of ADM was present when administered from 7 days before to 7 days after irradiation. BLM and CTX enhanced the radiation response at administration from 24 h before to 3 days after irradiation, and the effect of MM-C was observed when the drug was given from 24 h before to 24 h after irradiation. 5-FU, MTX and cis-DDP had no effect on the radiation response at any of the investigated intervals.

Animals↗
PubMed1986

Intracranial glossopharyngeal schwannoma, a tumour imitating an acoustic schwannoma.

Neurinomas originating from the ninth cranial nerve are rarely observed. The early signs and symptoms of a glossopharyngeal neurinoma are rather discrete, and it can happen that a tumour here will often first be recognised with the signs and symptoms of an expanding posterior fossa lesion--thus often closely resembling an acousticus neurinoma.

Cranial Nerve Neoplasms↗
PubMed1986

Major or local surgery for cure in early rectal and sigmoid carcinoma--a prospective evaluation.

The results of different types of treatment for early cancer in 158 out of 1,300 patients with rectal and sigmoid cancer were evaluated in a prospective study from 1979 to 1984. Radical surgery was performed in 121 patients (mean age 66 years) with cancer Dukes' A (median diameter 3 cm), while 37 patients (mean age 71) with smaller cancers (median 2 cm) had polypectomy or local excision. Post-operative complications were significantly more frequent in the first group. No patients in any of the two groups with carcinoma in pedunculated adenomas or within the upper half of the submucosa or above 9 cm from the anal verge had recurrent cancer. CEA-measurements had no prognostic value. No difference was found in crude or cancer-related death between the two groups. The overall results support the use of local treatment in elderly patients with complicating disease, having small cancers, not penetrating the tunica muscularis externa of the rectosigmoid wall.

Adenoma↗