| 1. |
- Brun, Eva, et al.
(författare)
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Early prediction of treatment outcome in head and neck cancer with 2-18FDG PET
- 1997
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 36:7, s. 741-747
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Tidskriftsartikel (refereegranskat)abstract
- The development of alternative treatment regimens in clinical oncology has increased the need for early prediction of cancer therapy outcome. The aim of this study was, early in the treatment phase, to identify patients with advanced head and neck cancer, responding or not responding to initiated therapy. The tumour metabolic rate of glucose (MRgl) examined by 2-18FDG-PET was determined in 17 patients before and after the first weeks of either radiotherapy (16-35 Gy) or one course of combination chemotherapy. Metabolic values uptake values normalized to plasma activity integrals--were correlated to loco-regional outcome, as evaluated 5-6 weeks after completion of treatment. Initial low tumour MRgl (<20 micromol/min/100 g tissue), in primary lesions or regional metastases, predicted a local complete response. When a high initial tumour MRgl was found, the magnitude of the reduction of MRgl in the second PET examination might be an adjunct in predicting local tumour response.
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| 2. |
- Kjellén, Elisabeth, et al.
(författare)
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A Phase I/II Evaluation of Metoclopramide as a Radiosensitiser in Patients with Inoperable Squamous Cell Carcinoma of the Lung
- 1995
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 31:13-14, s. 2196-2202
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Tidskriftsartikel (refereegranskat)abstract
- The feasibility of administering metoclopramide (MCA) as a radiosensitizer has been evaluated in 23 patients with a pathological or cytological diagnosis of a squamous cell carcinoma of the lung, clinically evaluated as inoperable. All patients received 40-60 Gy radiotherapy fractionated into 1.8 Gy fractions 5 times per week (Monday-Friday). Two MCA treatment regimens were used: (i) MCA at 2 mg/kg administered by intravenous infusion 1-2 h prior to radiotherapy 3 times per week (Monday, Wednesday, Friday); and (ii) MCA at 1 mg/kg administered by intravenous infusion 1-2 h prior to radiotherapy 5 times per week (Monday-Friday). 11 of the 23 patients treated with radiotherapy and MCA had none to mild pneumonitis or fibrosis and another 8 of the 23 had moderate levels. No patient had their therapy interrupted due to radiation-related side-effects. The MCA-related side-effects were as expected, i.e. 78% of the patients experienced sedation/tiredness and 48% expressed restlessness/anxiety symptoms. Both the total dose and serum levels of MCA were significantly associated to the MCA side-effect profile. Tumour response, duration of tumour response and survival were significantly positively correlated to the total and weekly doses of MCA administered to the patients during their radiotherapy treatment. These favourable phase II data have justified the initiation of a phase II/III randomised multicentred trial being carried out in Europe to evaluate MCA as a radiosensitiser.
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| 3. |
- Lindholm, C-E, et al.
(författare)
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Prognostic factors for tumour response and skin damage to combined radiotherapy and hyperthermia in superficial recurrent breast carcinomas
- 1995
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Ingår i: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 11:3, s. 337-355
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Tidskriftsartikel (refereegranskat)abstract
- Prognostic factors for complete tumour response and acute skin damage to combined hyperthermia and radiotherapy were analysed in material of patients with breast cancer, recurrent in previously irradiated areas. Radiotherapy was given daily to a total absorbed dose of 30.0 Gy in 2 weeks or 34.5 Gy in 3 weeks. The first radiotherapy schedule was combined with heat twice weekly, a total of four heat treatments (schedule A). The second radiotherapy schedule was combined with heat either once or twice a week resulting in a total of three (schedule B) or six (schedule C) heat treatments. Heat was induced with microwaves (2450, 915 or 434 MHz) via external applicators and always given after the radiotherapy fraction. The complete response (CR) rate in evaluable patients was 71% (49/69). There was no significant difference in CR rate between the three different hyperthermia schedules. The CR rates were 74% (14/19), 65% (15/23) and 74% (20/27) for schedules A, B and C respectively. The only factor predicting CR, evaluated both uni- and multivariately, was the CRE-value for the present radiotherapy dose (p = 0.02). If only tumours treated with 915 MHz were taken into account, however, then the highest minimum temperature at a given heat session predicted complete response (p = 0.03). This was true also in a multivariate analysis of this subgroup of tumours. A Kaplan-Meier analysis (log rank test) showed no significant difference in duration of CR between the different treatment schedules. Cox's proportional hazards method revealed three significant factors: tumour size (negatively correlated, p = 0.007), the time interval between the diagnosis of the primary tumour and the present treatment (p = 0.02) and the average temperature (0.03). Maximum acute skin reactions in the treatment field were scored according to an ordinal scale of 0-8, modified after WHO 1979. Twenty-six treatment areas (32%) expressed more severe skin damage (score > or = 5) in terms of desquamation with blisters (14%) and necrosis or ulceration (19%). Factors correlated with skin damage were the size of the lesion area (p = 0.011), the highest average maximum temperature during a given heat session (p = 0.03) and the fractionation schedule of hyperthermia (p = 0.05). The extent of previous radiotherapy absorbed dose, previous surgery in the treated area or previous chemotherapy had no significant influence on the acute skin reactions.
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| 4. |
- Rojas, A, et al.
(författare)
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Nicotinamide as a repair inhibitor in vivo: studies using single and fractionated X-ray doses in mouse skin and kidneys
- 1996
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Ingår i: Radiation Research. - 0033-7587. ; 145:4, s. 419-431
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitors of adenosine diphosphoribosyl transferase, like nicotinamide, 3-aminobenzamide and other analogues, can inhibit repair of radiation-induced sublethal and/or potentially lethal damage in some in vitro systems. Therefore, we have tested the effect of nicotinamide on repair parameters in vivo in two rodent normal tissues. In skin, the sensitivity to dose fractionation (1, 2, 5 or 10 X-ray fractions in 5 days) was monitored by defining the alpha/beta ratio in the presence or absence of nicotinamide (0.5 mg g-1) in air or carbogen. Pre- and postirradiation sensitization were investigated using an X-ray schedule of 5 fractions/5 days in carbogen alone or combined with nicotinamide given 1 h before, immediately after or 8 h after irradiation. Also, changes in the steepness of the underlying X-ray survival curve for the target skin clonogens, reflected by a change in the alpha/beta ratio, were investigated using the neutron top-up design. Underlying survival curves for oxygen +/- nicotinamide were obtained over the X-ray dose range 2.5 to 25 Gy, by administering single X-ray doses and following these with single top-up doses of d(4)-Be neutrons. Finally, in mouse kidney, recovery half-times (t1/2) were obtained by determining the time-dependent disappearance of X-ray damage using a split-dose design of two 6-Gy fractions separated by an interval which varied from 0 to 48 h and followed by two top-up doses from a neutron beam. No increase in alpha/beta for epidermal damage was seen with nicotinamide alone and, although sensitization was observed when the drug was given 1 h before irradiation, no postirradiation sensitization was detected. In kidney, there was no significant difference in the proportion of total repairable damage or in the half-life of recovery between treatments given with or without nicotinamide. Therefore, no decrease in normal tissue tolerance should be observed with the use of nicotinamide in clinical radiotherapy resulting either from reduced sparing with dose fractionation or from an increase in residual damage when shortening the interfraction interval. Finally, unless repair of radiation damage in normal tissues in vivo differs markedly from that of tumors, it is unlikely that the large sensitization seen in rodent tumors at 1.5 to 2 Gy per fraction, with carbogen and nicotinamide, can be attributed to nicotinamide acting as a repair inhibitor.
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| 5. |
- Zätterstrom, Ulf K, et al.
(författare)
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Radiation effects on S-phase duration, labelling index, potential doubling time and DNA distribution in head and neck cancer xenografts
- 1995
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 34:2, s. 205-211
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Tidskriftsartikel (refereegranskat)abstract
- The effect of irradiation on S-phase duration (Ts), labelling index (LI), potential doubling time (Tpot), and cell cycle phase distributions was determined by DNA flow cytometry in xenografted human squamous cell carcinoma of the head and neck (SCCHN). Tumours were treated with a single dose of 3 Gy, and excised at intervals over a 90-h period. Six hours before each excision the tumours were labelled in vivo with bromodeoxyuridine (BrdUrd). Although the growth rate of irradiated tumours was comparable with that of untreated controls, analysis of BrdUrd uptake revealed a transient reduction of LI and a prolongation of Ts in irradiated tumours. Maximum mean Tpot was 931 days in irradiated tumours as compared to 13 days in untreated controls. The variations in Ts, LI and Tpot all occurred within the first hours after irradiation; during the remainder of the observation time, the values of the variables did not differ from those of untreated controls. In irradiated tumours the distribution of cells according to DNA content changed significantly on three occasions during the observation period: 1) Parallel to the initial lowering of LI and prolongation of Ts there was a transient increase in the proportion of cells in G0/G1 and a decrease in the proportion of cells in S and G2; 2) At 18 h, the most pronounced cell cycle phase redistribution occurred when the G0/G1 fraction decreased and the S and G2 phase fractions increased; 3) At 66 h (i.e., approximately one cell cycle later), the pattern was the same as that after 18 h. The findings suggest that the transient prolongation of DNA replication seen in SCCHN cells immediately after a single radiation dose is a symptom of DNA damage inflicted during late G1 or early S-phase, and that this disturbance in DNA synthesis is associated with the subsequent accumulation of cells in G2 phase.
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