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Biomedical subjects

G Lundell

Publications and source records attributed to G Lundell.

At least 37 records · Page 2Linked to original sources
PubMed1995

Different dose regimens of 5-fluorouracil and interferon-alpha in patients with metastatic colorectal carcinoma.

Three different 5-fluorouracil (5-FU)-interferon-alpha-2b (IFN)-containing regimens were designed for treatment of patients with advanced colorectal cancer. 87 patients with a Karnofsky index > or = 70 were included in three sequential non-randomised phase II trials. Regimen A consisted of 5-FU (750 mg/m2/day) given as a continuous infusion on days 1-5 followed by weekly 1-h intravenous infusions until week 8. IFN (5 MU) was given subcutaneously on days 1, 3 and 5 followed by injections (9 MU) every second day until week 8. The cycle was then repeated. Regimen B consisted of 5-FU (750 mg/m2/day) given as a continuous infusion on days 1-5 followed by 5-min intravenous injections on days 12 and 19. IFN (3 MU) was given subcutaneously on days 1-5 followed by injections (5 MU) on days 11-13 and 18-20. The cycle was repeated every fourth week. Regimen C consisted of 5-FU (750 mg/m2/day) given as a continuous infusion on days 1-5. IFN (3 MU) was given subcutaneously on days 1-5. The cycle was repeated every third week. The objective response rates (complete response (CR) and partial response (PR)) after approximately 4 months of therapy or longer were as follows: regimen A (n = 27) 22% (2 CR, 4 PR), regimen B (n = 33) 42% (4 CR, 10 PR) and regimen C (n = 27) 22% (1 CR, 5 PR). The corresponding response figures for previously untreated patients were regimen A 50%, regimen B 64% and regimen C 38%. Response durations varied from a few weeks up to 142 + weeks. Toxicities were generally mild and reversible, and the treatments were convenient for the patients and cost effective since the 5-day infusions could be given by a portable pump without hospitalisation. Our results are in agreement with those of others showing that 5-FU/IFN combinations can be highly effective in advanced colorectal cancer, and that a number of factors such as doses, dose intensities, infusion rates and timing of the two drugs may be crucial for the anti-tumour activity of this drug combination.

Adult↗
PubMed1994

Combined doxorubicin, hyperfractionated radiotherapy, and surgery in anaplastic thyroid carcinoma. Report on two protocols. The Swedish Anaplastic Thyroid Cancer Group.

BACKGROUND: Anaplastic carcinoma of the thyroid (ACT) rarely can be cured, but every effort should be made to improve prognosis and, above all, prevent death due to suffocation or large local tumor ulceration. METHODS: From 1984 to 1992, 33 consecutive patients with ACT were treated prospectively according to a combined treatment program consisting of hyperfractionated radiotherapy, doxorubicin, and debulking surgery. Preoperative radiotherapy was administered to a target dose of 30 Gy and postoperatively to a total dose of 46 Gy. Radiotherapy was performed 5 days a week. The daily fraction was 1.0 Gy x 2 until 1988, after which it was 1.3 Gy x 2. Otherwise, the therapy remained unchanged. Twenty milligrams of doxorubicin were administered intravenously per week. Debulking surgery was possible in 23 patients (70%). RESULTS: No patient failed to complete the protocol because of toxicity. There were no signs of local recurrence in 16 patients (48%). In only eight patients (24%) was death attributed to local failure. In four patients, survival with no evidence of disease exceeded 2 years. Improvement in local tumor control was marginally significant (P = 0.08) in the 17 patients treated in the latter part of the study, with no sign of local disease in 11 patients and deaths due to local failure in only 2 patients. The improved local control could not be attributed to any differences between the two series. CONCLUSION: Combination modality treatment of ACT is feasible and effective despite the patients' advanced age and locally advanced disease. There was a tendency for local control to be improved after accelerated radiotherapy.

Aged↗
PubMed1994

Does early administration of thyroxine reduce the development of Graves' ophthalmopathy after radioiodine treatment?

The roles of thyroid hormones and thyrotropin (TSH) in the development of Graves' ophthalmopathy are not clear. Some studies suggest a protective effect of thyroid hormones on experimental exophthalmos and an adverse effect of increased TSH levels. In September 1988 we introduced early thyroxine (T4) administration after 131I therapy for hyperthyroidism caused by Graves' disease. We carried out a retrospective study of records from all patients with this disease treated with 131I for 4 years. During the first 2 years 248 patients were treated (group A). They received T4 when the serum concentration of TSH and/or T4 indicated hypothyroidism. During the next 2 years 244 patients were treated (group B). They were all given 0.05 mg of T4 daily, starting 2 weeks after therapy, and 0.1 mg after a further 2 weeks. With a follow-up of 18 months, 45 patients (18%) in group A and 27 patients (11%) in group B developed or deteriorated in an already present ophthalmopathy (p = 0.03, relative risk = 1.64, 95% confidence interval = 1.05-2.55). Twenty-six patients in group A required specific therapy for the ophthalmopathy (e.g. antithyroid drugs, steroids, etc.) compared to 11 patients in group B (p = 0.02, relative risk = 2.33; 95% confidence interval = 1.18-4.60). Our results suggest that early administration of T4 after 131I therapy reduces the occurrence of Graves' ophthalmopathy.

Confidence Intervals↗
PubMed1994

Standardized precision radiotherapy in choroidal metastases.

Metastases in the choroid of the eye are frequent in patients with disseminated malignancy. We here report the results using the precision radiotherapy technique described by Schipper et al. to treat 14 of 17 consecutive patients (21 eyes) with symptoms from such metastases. A beam defining collimator was used and a lateral field was given with the treated eye individually fixed. Varying fractionations and doses were used. The biologically effective dose for early effects (BED3) was 47 to 90 Gy and for late effects (BED10) 28 to 59 Gy. In 14 eyes (82%) the metastases regressed completely. The visual acuity was stabilized or improved in all patients and none needed local surgery. Three patients developed signs of radiation retinopathy, but only in one case the visual function was compromised. With this standardized technique no individualized dose planning was needed, the risk of radiation cataract was minimized and a dry eye avoided.

Adolescent↗
PubMed1993

Mortality in patients treated for hyperthyroidism with iodine-131.

Causes of death were studied in 10,552 Swedish hyperthyroid patients treated with 131I diagnosed between 1950 and 1975. The patients were followed for an average of 15 years (range 0-35 years) and were matched with the Swedish Cause of Death Register. A total of 5,400 deaths were observed and the overall standardized mortality ratio was 1.47 (95% confidence interval (CI) 1.43-1.51). The standardized mortality ratio for females was 1.50 (95% CI 1.46-1.55) compared to 1.31 (95% CI 1.23-1.39) in males. The most common cause of death (61%) was from cardiovascular diseases (standardized mortality ratio 1.65; 95% CI 1.59-1.71). Significantly elevated risks were also seen for tumours, diseases of the endocrine system, respiratory system, gastro-intestinal system, and congenital malformations. In all causes of death, except tumours and trauma, decreasing standardized mortality ratios over time were seen. Patients followed for more than 10 years had significantly elevated risks for tumours, diseases of the endocrine, respiratory, and cardiovascular systems. Patients given higher 131I activity and younger patients had higher standardized mortality ratios than those given lower activity and older patients. The hyperthyroidism per se, rather than the 131I treatment, appeared to be the major explanation for the elevated mortality.

Adolescent↗
PubMed1993

Graves' ophthalmopathy and tobacco smoking.

We have studied the smoking habits in a group of patients with hyperthyroidism caused by Graves' disease. One hundred and seventy-one patients were randomized to different forms of treatment for hyperthyroidism and the outcome of this study concerning Graves' ophthalmopathy has been described previously. There were 89 smokers (52%) and 82 non-smokers (48%). Among the smokers there were 32 patients (19%) who developed ophthalmopathy or deteriorated in an already present ophthalmopathy and 57 patients who did not (33%), whereas among the non-smokers, 14 (8%) had ophthalmopathy during the study and 68 (40%) did not (p = 0.006). We could not obtain statistical significance when trying to demonstrate that smoking is a risk factor for the development of ophthalmopathy after treatment for hyperthyroidism. It was noted that smokers had higher pretreatment levels of thyrotropin-receptor antibodies (p = 0.027). In conclusion, these results support the previously described association between smoking and Graves' ophthalmopathy.

Adult↗
PubMed1992

Leukaemia incidence after iodine-131 exposure.

Leukaemia is one of the most prominent late effects of exposure to ionising radiation. We have studied the incidence of leukaemia among 46,988 Swedish patients exposed to iodine-131 (131I) for diagnostic reasons or to treat hyperthyroidism or thyroid cancer. The observed number of leukaemias was compared with that expected based on incidence data from the general population. The mean absorbed dose to the bone marrow was estimated as 14 mGy (range 0.01-2.226). 195 leukaemias occurred more than 2 years after exposure, and the standardised incidence ratio (SIR) was 1.09 (95% confidence interval 0.94-1.25). Similar, but again not significantly, increased risks were seen for chronic lymphocytic leukaemia (CLL) (SIR = 1.08), a malignant condition not found to be increased after irradiation, and for non-CLL (SIR = 1.09). The risk of leukaemia did not vary by sex, age, time, or radiation dose from 131I. One reason for the absence of a radiation effect, other than chance, includes the possible lowering of risk when exposure is protracted over time as occurs with 131I. Excess leukaemia risks of more than 25% could thus be excluded with high assurance in this population of mainly adults. These results should be reassuring to patients exposed to 131I in medical practice and to most individuals exposed to the fall-out from the Chernobyl accident.

Adolescent↗
PubMed1992

Occurrence of ophthalmopathy after treatment for Graves' hyperthyroidism. The Thyroid Study Group.

BACKGROUND: Ophthalmopathy caused by Graves' disease may first appear or worsen during or after treatment for hyperthyroidism. It is not known, however, whether choosing to treat hyperthyroidism with antithyroid drugs, iodine-131, or surgery affects the development or aggravation of Graves' ophthalmopathy. METHODS: We studied 168 patients with hyperthyroidism caused by Graves' disease, stratified into two age groups--20 to 34 years (54 patients, group 1) and 35 to 55 years (114 patients, group 2). The patients in group 1 were randomly assigned to treatment with methimazole for 18 months or subtotal thyroidectomy, and those in group 2 to either of these two treatments or to iodine-131 therapy. All the patients received thyroxine to avert hypothyroidism, except those treated with iodine-131, who received thyroxine only if hypothyroidism developed. The duration of follow-up was at least 24 months. RESULTS: Twenty-two patients (13 percent) had infiltrative Graves' ophthalmopathy at randomization. During follow-up, ophthalmopathy developed for the first time in 22 patients (13 percent) and worsened in 8 patients (5 percent). The frequency of the development or worsening of ophthalmopathy was similar among the patients in group 1 (medical therapy, 4 of 27 patients [15 percent]; and surgery, 3 of 27 patients [11 percent]). In group 2, ophthalmopathy developed or worsened in 4 of the 38 patients (10 percent) treated medically, 6 of the 37 patients (16 percent) treated surgically, and 13 of the 39 patients (33 percent) given iodine-131 (P = 0.02 for the comparison between the iodine-131 subgroup and the others combined). The risk of the development or worsening of ophthalmopathy increased as pretreatment serum triiodothyronine concentrations increased. CONCLUSIONS: As compared with other forms of antithyroid therapy, iodine-131 is more likely to be followed by the development or exacerbation of Graves' ophthalmopathy.

Adult↗
PubMed1992

Cancer mortality after iodine-131 therapy for hyperthyroidism.

Cancer mortality was studied in 10,552 Swedish hyperthyroid patients treated with 131I between 1950 and 1975. The patients were matched with the Swedish Cause-of-Death Register and the cases of 977 patients who died from cancer or leukemia were studied. The patients had been followed up for an average of 15 years (range 0 to 35 years), and the overall standardized mortality ratio (SMR) was 1.09 [95% confidence interval (CI) = 1.03 to 1.16], with a higher risk for women. The highest mortality was seen during the first year after exposure (SMR = 1.15) and decreased for the following 9 years (SMR = 1.04). The risk of dying from a cancer in the digestive tract and respiratory organs was significantly elevated more than 10 years after exposure, as was the overall cancer mortality (SMR = 1.14). No increased risk was seen for leukemia, bladder cancer or breast cancer. Younger patients and those receiving 131I at higher activity had higher SMRs than older patients and those receiving lower activity. Patients with toxic nodular goiter had higher risk than those with Graves' disease. The lack of increasing mortality over time and with increasing activity of 131I administered argues against a carcinogenic effect of 131I. However, in the case of cancers of the stomach, the 131I exposure could have contributed to the excess mortality from these cancers.

Age Factors↗
PubMed1992

Tumors after radiotherapy for thyroid cancer. A case-control study within a cohort of thyroid cancer patients.

A case-control study of Swedish thyroid cancer patients was conducted to evaluate the possible influence of 131I treatment and external radiotherapy on the risk of developing a subsequent cancer. Both cases and controls derived from a cohort of Swedish thyroid cancer patients treated with 131I (n = 834) or by other means (n = 1,121). Thirty-six breast, 13 stomach, 12 kidney, and 5 bladder cancers were found more than 2 years after 131I treatment/thyroid cancer diagnosis. Individual, absorbed dose in the organs was calculated by using ICRP tables, administered activity of 131I, and 24-h 131I uptake. In studying the effect of 131I and external radiotherapy no statistically significant dose-response relationships were found for cancers of the breast, stomach, bladder or kidney. When the absorbed dose from 131I was analyzed separately the risks remained essentially the same. The present follow-up time and the relatively low absorbed dose that the patients received from 131I and external radiotherapy necessitate studies with a longer follow-up time or a larger patient material before more firm conclusions can be made.

Adolescent↗
PubMed1992

Addition of nuclear DNA content to the AMES risk-group classification for papillary thyroid cancer.

BACKGROUND: The purpose of this study was to prospectively assess whether nuclear DNA content added prognostic value to existing risk factors in patients with papillary thyroid cancer. METHODS: Nuclear DNA content was measured both on the fine needle aspiration material and the surgical specimen in 73 patients with primary or recurrent papillary thyroid cancer. We modified the existing age of patient, presence of distant metastases, extent and size of the tumor (AMES) risk-group classification to include DNA ploidy with AMES (DAMES). Patients with euploid tumors that were AMES low risk were considered to be DAMES low risk; patients with euploid tumors that were AMES high risk became intermediate risk, and patients with aneuploid tumors that were AMES high risk became DAMES high risk. RESULTS: Forty-eight patients were in the DAMES low-risk group. Recurrences and/or distant metastases developed in only four (8%) of these patients. Twenty-two patients were in the DAMES intermediate-risk group. Twelve (55%) of the intermediate-risk group had residual, recurrent, or distant metastatic disease, with one death from cancer at 120 months. Three patients were in the DAMES high-risk group. Distant metastases developed in all three patients, who died within 24 months from thyroid cancer. A statistically significant difference existed in the development of recurrence/metastases or death from cancer in the DAMES high-risk group compared with the other risk groups combined. CONCLUSIONS: Nuclear DNA content adds prognostic value to the existing AMES risk-group classification. Because DNA analysis on fine needle aspiration correlated well with the surgical specimen DNA analysis, this modified classification can be used perioperatively to further individualize the treatment of patients with papillary thyroid cancer.

Adult↗
PubMed1991

Cancer risk after iodine-131 therapy for hyperthyroidism.

Cancer incidence was studied in 10,552 patients (mean age, 57 years) who received 131I therapy (mean dose, 506 MBq) for hyperthyroidism between 1950 and 1975. Follow-up on these patients was continued for an average of 15 years. Record linkage with the Swedish Cancer Register for the period 1958-1985 identified 1543 cancers occurring 1 year or more after 131I treatment, and the standardized incidence ratio (SIR) was 1.06 (95% confidence interval = 1.01-1.11). Significantly increased SIRs were observed for cancers of the lung (SIR = 1.32; n = 105) and kidney (SIR = 1.39; n = 66). Among 10-year survivors, significantly elevated risks were seen for cancers of the stomach (SIR = 1.33; n = 58), kidney (SIR = 1.51; n = 37), and brain (SIR = 1.63; n = 30). Only the risk for stomach cancer, however, increased over time (P less than .05) and with increasing activity administered (P = not significant). The risk for malignant lymphoma was significantly below expectation (SIR = 0.53; n = 11). Overall cancer risk did not increase with administered 131I dose or with time since exposure. The absence of any increase in leukemia adds further support to the view that a radiation dose delivered gradually over time is less carcinogenic than the same total dose received over a short time. Only for stomach cancer was a possible radiogenic excess suggested.

Adolescent↗
PubMed1991

External irradiation of growth hormone producing pituitary adenomas: prolactin as a marker of hypothalamic and pituitary effects.

Fifty-six patients with acromegaly were treated with external irradiation, 50 Gy, after unsuccessful pituitary surgery. A 50% reduction of pre-irradiation growth hormone levels was obtained in 51/56 patients. This level was reached after 26 +/- 14 months in 33 patients with prolactin levels less than 25 micrograms/l at diagnosis, after 21 +/- 17 months in 18 patients with prolactin greater than or equal to 25 micrograms/l, and after 20 +/- 21 months in 12 patients with prolactin greater than 40 micrograms/l at diagnosis. A further 50% decrease of growth hormone levels was obtained in 40/51 patients 42 +/- 22 months after radiotherapy, indicating that in clearly responsive patients, the growth hormone depression after radiotherapy follows a first order reaction. Four patients did not reach a 50% reduction of growth hormone levels 48-80 months after radiotherapy. During 10 years of follow-up, the growth hormone depression tended to be more pronounced in patients with mixed secretion of growth hormone and prolactin. The reduction of growth hormone levels was not correlated with the irradiated volume or the cumulative radiation effect. Within the first year, prolactin increased within the normal range in normoprolactinemic patients and remained so during follow-up. In hyperprolactinemic patients, prolactin decreased successively but to a lesser extent than growth hormone. Pituitary insufficiencies increased over time and three patients developed GH-insufficiency. Hypothalamic damage as indicated by prolactin changes was a regular phenomenon after radiotherapy.

Acromegaly↗
PubMed1991

Cancer risks in thyroid cancer patients.

Cancer risks were studied in 834 thyroid cancer patients given 131I (4,551 MBq, average) and in 1,121 patients treated by other means in Sweden between 1950 and 1975. Record-linkage with the Swedish Cancer Register identified 99 new cancers more than 2 years after 131I therapy [standardised incidence ratio (SIR) = 1.43; 95% confidence interval (CI) 1.17-1.75] vs 122 (SIR = 1.19; 95% CI 0.88-1.42) in patients not receiving 131I. In females treated with 131I overall SIR was 1.45 (95% CI 1.14-1.83) and significantly elevated were noted for tumours of the salivary glands, genital organs, kidney and adrenal gland. No elevated risk of a subsequent breast cancer or leukaemia was noted. SIR did not change over time, arguing against a strong radiation effect of 131I. Organs that were estimated to have received more than 1.0 Gy had together a significantly increased risk of a subsequent cancer following 131I treatment (SIR = 2.59; n = 18). A significant trend was seen for increasing activities of 131I with highest risk for patients exposed to greater than or equal to 3,664 MBq (SIR = 1.80; 95% CI 1.20-2.58). No specific cancer or group of cancers could be convincingly linked to high-dose 131I exposures since SIR did not increase after 10 years of observation. However, upper confidence intervals could not exclude levels of risk that would be predicted based on data from the study of atomic bomb survivors. We conclude that the current practice of extrapolating the effects of high-dose exposures to lower-dose situations is unlikely to seriously underestimate radiation hazards for low LET radiation.

Female↗
PubMed1990

Anaplastic thyroid carcinoma. Doxorubicin, hyperfractionated radiotherapy and surgery.

Sixteen consecutive patients with anaplastic carcinoma of the thyroid were prospectively treated according to a combined regimen consisting of hyperfractionated radiotherapy, doxorubicin and debulking surgery. The radiotherapy was preoperatively administered to a target dose of 30 Gy in 3 weeks, and postoperatively to an additional dose of 16 Gy in 1.5 weeks. Radiotherapy was administered twice daily, 5 days a week, with a target dose of 1 Gy per fraction and with a minimum interval of 6 hours. A dose of 20 mg doxorubicin was administered intravenously 1 to 2 hours before the first radiotherapy session every week. Debulking surgery was feasible in 9 patients. Local complete remission was achieved in 5 patients and 3 of these are still alive disease-free at 10, 30, and 30 months respectively after diagnosis. Only 6 patients succumbed to a local failure. This combination regimen was well tolerated despite the patients' high age and advanced disease.

Aged↗