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- Fransson, P., et al.
(författare)
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Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): patient-reported quality-of-life outcomes of a randomised, controlled, 3 trial
- 2021
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Ingår i: Lancet Oncology. - : Elsevier BV. - 1470-2045. ; 22:2, s. 235-245
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Tidskriftsartikel (refereegranskat)abstract
- Background The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was non-inferior to conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation and ultra-hypofractionation up to 6 years after treatment in the HYPO-RT-PC trial. Methods HYPO-RT-PC is a multicentre, open-label, randomised, controlled, non-inferiority, phase 3 trial done in 12 centres (seven university hospitals and five county hospitals) in Sweden and Denmark. Inclusion criteria were histologically verified intermediate-to-high-risk prostate cancer (defined as T1c-T3a with one or two of the following risk factors: stage T3a; Gleason score >= 7; and prostate-specific antigen 10-20 ng/mL with no evidence of lymph node involvement or distant metastases), age up to 75 years, and WHO performance status 0-2. Participants were randomly assigned (1:1) to conventional fractionation (78.0 Gy in 39 fractions, 5 days per week for 8 weeks) or ultra-hypofractionation (42.7 Gy in seven fractions, 3 days per week for 2.5 weeks) via a minimisation algorithm with stratification by trial centre, T-stage, Gleason score, and prostate-specific antigen. QOL was measured using the validated Prostate Cancer Symptom Scale (PCSS) and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years. The primary endpoint (failure-free survival) has been reported elsewhere. Here we report QOL, a secondary endpoint analysed in the perprotocol population, up to 6 years after radiotherapy. The HYPO-RT-PC trial is registered with the ISRCTN registry, ISRCTN45905321. Findings Between July 1, 2005, and Nov 4, 2015, 1200 patients were enrolled and 1180 were randomly assigned (conventional fractionation n=591, ultra-hypofractionation n=589); 1165 patients (conventional fractionation n=582, ultra-hypofractionation n=583) were included in this QOL analysis. 158 (71%) of 223 patients in the conventional fractionation group and 146 (66%) of 220 in the ultra-hypofractionation group completed questionnaires at 6 years. The median follow-up was 48 months (IQR 25-72). In seven of ten bowel symptoms or problems the proportion of patients with clinically relevant deteriorations at the end of radiotherapy was significantly higher in the ultra-hypofractionation group than in the conventional fractionation group (stool frequency [p<0.0001], rush to toilet [p=0.0013], flatulence [p=0.0013], bowel cramp [p<0.0001], mucus [p=0.0014], blood in stool [p<0.0001], and limitation in daily activity [p=0.0014]). There were no statistically significant differences in the proportions of patients with clinically relevant acute urinary symptoms or problems (total 14 items) and sexual functioning between the two treatment groups at end of radiotherapy. Thereafter, there were no clinically relevant differences in urinary, bowel, or sexual functioning between the groups. At the 6-year followup there was no difference in the incidence of clinically relevant deterioration between the groups for overall urinary bother (43 [33%] of 132 for conventional fractionation vs 33 [28%] of 120 for ultra-hypofractionation; mean difference 5.1% [95% CI -4.4 to 14.6]; p=0.38), overall bowel bother (43 [33%] of 129 vs 34 [28%] of 123; 5.7% [-3.8 to 15.2]; p=0.33), overall sexual bother (75 [60%] of 126 vs 59 [50%] of 117; 9.1% [-1.4 to 19.6]; p=0.15), or global health/QOL (56 [42%] of 134 vs 46 [37%] of 125; 5.0% [-5.0 to 15.0]; p=0.41). Interpretation Although acute toxicity was higher for ultra-hypofractionation than conventional fractionation, this long-term patient-reported QOL analysis shows that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after completion of treatment. These findings support the use of ultra-hypofractionation radiotherapy for intermediate-to-high-risk prostate cancer.
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- Widmark, A., et al.
(författare)
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Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial
- 2019
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 394:10196, s. 385-395
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Tidskriftsartikel (refereegranskat)abstract
- Background Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RTPC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation. Methods In this open-label, randomised, phase 3 non-inferiority trial done in 12 centres in Sweden and Denmark, we recruited men up to 75 years of age with intermediate-to-high-risk prostate cancer and a WHO performance status between 0 and 2. Patients were randomly assigned to ultra-hypofractionation (42.7 Gy in seven fractions, 3 days per week for 2.5 weeks) or conventional fractionated radiotherapy (78.0 Gy in 39 fractions, 5 days per week for 8 weeks). No androgen deprivation therapy was allowed. The primary endpoint was time to biochemical or clinical failure, analysed in the per-protocol population. The prespecified non-inferiority margin was 4% at 5 years, corresponding to a critical hazard ratio (HR) limit of 1.338. Physician-recorded toxicity was measured according to the Radiation Therapy Oncology Group (RTOG) morbidity scale and patient-reported outcome measurements with the Prostate Cancer Symptom Scale (PCSS) questionnaire. This trial is registered with the ISRCTN registry, number ISRCTN45905321. Findings Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionation (n=602) or ultra-hypofractionation (n=598), of whom 1180 (591 conventional fractionation and 589 ultra-hypofractionation) constituted the per-protocol population. 1054 (89%) participants were intermediate risk and 126 (11%) were high risk. Median follow-up time was 5.0 years (IQR 3.1-7.0). The estimated failure-free survival at 5 years was 84% (95% CI 80-87) in both treatment groups, with an adjusted HR of 1.002 (95% CI 0.758-1.325; log-rank p=0.99). There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy (158 [28%] of 569 patients vs 132 [23%] of 578 patients; p=0.057). There were no significant differences in grade 2 or worse urinary or bowel late toxicity between the two treatment groups at any point after radiotherapy, except for an increase in urinary toxicity in the ultra-hypofractionation group compared to the conventional fractionation group at 1-year follow-up (32 [6%] of 528 patients vs 13 [2%] of 529 patients; (p=0.0037). We observed no differences between groups in frequencies at 5 years of RTOG grade 2 or worse urinary toxicity (11 [5%] of 243 patients for the ultra-hypofractionation group vs 12 [5%] of 249 for the conventional fractionation group; p=1.00) and bowel toxicity (three [1%] of 244 patients vs nine [4%] of 249 patients; p=0.14). Patient-reported outcomes revealed significantly higher levels of acute urinary and bowel symptoms in the ultra-hypofractionation group compared with the conventional fractionation group but no significant increases in late symptoms were found, except for increased urinary symptoms at 1-year follow-up, consistent with the physician-evaluated toxicity. Interpretation Ultra-hypofractionated radiotherapy is non-inferior to conventionally fractionated radiotherapy for intermediate-to-high risk prostate cancer regarding failure-free survival. Early side-effects are more pronounced with ultra-hypofractionation compared with conventional fractionation whereas late toxicity is similar in both treatment groups. The results support the use of ultra-hypofractionation for radiotherapy of prostate cancer. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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- Andersson, P. S., et al.
(författare)
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TISSUE CHARACTERIZATION USING LASER-INDUCED FLUORESCENCE.
- 1987
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Ingår i: Conference on Lasers and Electro-Optics. - 0936659491 ; 14, s. 46-48
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Konferensbidrag (refereegranskat)abstract
- In cancer tumor detection, tissue autofluorescence and characteristic features of injected hematoporphyrin derivative (HPD) can be utilized. The authors have studied the importance of the excitation wavelength for the achievable contrast between tumor and surrounding tissue using a rat tumor model. They have also compared the relative merits of two HPD preparations for tumor fluorescence detection. The real-time capability of the fluorescence technique is discussed.
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- Holm, L, et al.
(författare)
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Identification of the minimal glycopeptide core recognized by T cells in a model for rheumatoid arthritis
- 2005
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Ingår i: Bioorganic & Medicinal Chemistry. - Oxford : Elsevier BV. - 0968-0896 .- 1464-3391. ; 13:2, s. 473-482
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Tidskriftsartikel (refereegranskat)abstract
- Collagen induced arthritis (CIA) is a common mouse model for rheumatoid arthritis. Two sets of truncated peptides derived from type II collagen have been prepared and tested for binding to A(q), a MHC-II molecule associated with development of CIA. Binding to A(q) correlated well with predictions from a computer-based model. T-cell hybridomas, obtained in CIA, were also used to study the ability of A(q) bound peptides to trigger a T-cell response. The minimal peptide epitope required for binding, as well as for giving a T-cell response, was determined to be CII260-267. In collagen this epitope is often glycosylated at hydroxylysine 264 and glycosylation has been shown to be an immunodominant feature in CIA. Synthesis and evaluation of CII260-267 carrying a beta-D-galactosyl moiety at position 264 revealed that this glycopeptide stimulated representative members from a panel of carbohydrate-specific T-cell hybridomas obtained in CIA.
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- Killander, F, et al.
(författare)
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No increased cardiac mortality or morbidity of radiotherapy in breast cancer patients after breast conserving surgery: 20 years follow-up of the randomised x trial.
- 2020
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 107:4, s. 701-9
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Tidskriftsartikel (refereegranskat)abstract
- Radiotherapy (RT) after breast conserving surgery reduces loco-regional recurrences and improves survival, but may cause late side effects. The main purpose of this paper was to investigate long-term side effects after whole breast RT in a randomised clinical trial initiated in 1991 and to report dose-volume data based on individual 3D treatment plans for organs at risk (OR).The trial included 1187 T1-2 N0 breast cancer patients randomised to postoperative tangential whole breast radiotherapy or no further treatment. The prescription dose to the clinical target volume was 48-54 Gy. We present 20 year follow-up on survival, cause of death, morbidity and later malignancies. For a cohort of patients (n=157) with accessible CT-based 3D treatment plans in Dicom-RT format, dose-volume descriptors for OR were derived. In addition, these were compared with dose-volume data for a cohort of patients treated with contemporary RT techniques.The cumulative incidence of cardiac mortality was 12.4 % in the control group and 13.0 % in the RT group (P= 0.8). There was an increase in stroke mortality, 3.4 % in the control group versus 6.7 % in the RT group (P=0.018). Incidences of contra lateral breast cancer and lung cancer were similar between groups. The median Dmean (range) heart dose for left-sided treatments was 3.0 Gy (1.1-8.1) and the corresponding value for patients treated in 2017 was 1.5 Gy (0.4-6.0).In this trial serious late side effects of whole breast radiotherapy were limited and less than previously reported in large meta-analyses. We observed no increased cardiac mortality in irradiated patients with doses to the heart were median Dmean 3.0 Gy for left-sided RT. The observed increase in stroke mortality may partly be secondary to cardiac side effects, complications to anticoagulant treatment, or to chance, rather than a direct side effect of tangential whole breast irradiation.
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- Lindqvist, Anna-Karin, et al.
(författare)
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Influence on spontaneous tissue inflammation by the major histocompatibility complex region in the nonobese diabetic mouse.
- 2005
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 61:2, s. 119-127
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the role of the major histocompatibility complex (MHC) region in the specificity of autoimmunity by analysing specifically the development of sialadenitis, but also insulitis, nephritis and autoantibody production in autoimmune-prone nonobese diabetic (NOD) mice where the MHC H2g7 haplotype had been exchanged for the H2q (NOD.Q) or H2p (NOD.P) haplotype. The exchange of H2 haplotype did not affect the frequency of sialadenitis because the H2q and H2p congenic NOD strains developed sialadenitis with the same incidence as NOD. However, the severity of sialadenitis varied among the strains, as NOD.Q > NOD > NOD.P. At 11–13 weeks of age, the NOD.Q (H2q) female mice developed more severe sialadenitis compared to NOD.P (H2p) (P = 0.038). At 20 weeks, the NOD (H2g7) female mice showed more severe sialadenitis than NOD.P (P = 0.049). This is in contrast to the development of insulitis in the present strains, because the incidence of insulitis was almost completely inhibited by the replacement of the H2g7 haplotype of NOD. The incidence of insulitis in NOD.Q was 11–22%, compared to 75% in NOD, which correlated well with lower titres of anti-glutamic acid decarboxylase (anti-GAD) antibodies in NOD.Q compared to NOD (P = 0.009). However, the introduction of the H2q haplotype into the NOD strain instead directed the autoimmune response towards the production of lupus types of autoantibodies, because the incidence of antinuclear antibodies (ANA) in NOD.Q was 89% compared with 11% in NOD.P and 12% in NOD mice, which in turn correlated with a high incidence of nephritis in NOD.Q compared to NOD. Consequently, we show that different haplotypes of MHC are instrumental in directing the specificity of the spontaneous autoimmune inflammation. This article is cited by:
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- Rojas, Ana Maria, et al.
(författare)
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Nicotinamide as a repair inhibitor in vivo: single and fractionated X-ray dose studies in mouse skin and kidneys
- 1996
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 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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