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- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- Alkner, Sara, et al.
(författare)
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Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases - an open, multicentre, randomised non-inferiority phase 3 trial.
- 2023
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Ingår i: BMJ open. - 2044-6055. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- Modern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer. Therefore, there is a need to individualise regional RT in relation to the risk of recurrence.In this multicentre, prospective randomised trial, clinically node-negative patients with oestrogen receptor-positive, HER2-negative BC and 1-2 SLN macrometastases are eligible. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axilla level I-III, the supraclavicular fossa and in selected patients the internal mammary nodes. Both groups receive RT to the remaining breast. Chest-wall RT after mastectomy is given in the standard arm, but in the intervention arm only in cases of widespread multifocality according to national guidelines. RT quality assurance is an integral part of the trial.The trial aims to include 1350 patients between March 2023 and December 2028 in Sweden and Norway. Primary outcome is recurrence-free survival (RFS) at 5years. Non-inferiority will be declared if outcome in the de-escalation arm is not >4.5percentage units below that with regional RT, corresponding to an HR of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity and health-related quality of life. Gene expression analysis and tumour tissue-based studies to identify prognostic and predictive markers for benefit of regional RT are included.The trial protocol is approved by the Swedish Ethics Authority (Dnr-2022-02178-01, 2022-05093-02, 2023-00826-02, 2023-03035-02). Results will be presented at scientific conferences and in peer-reviewed journals.NCT05634889.
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- Alkner, Sara, et al.
(författare)
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The role of AIB1 and PAX2 in primary breast cancer: validation of AIB1 as a negative prognostic factor.
- 2013
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 24:5, s. 1244-1252
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe steroid-receptor coactivator amplified in breast cancer one (AIB1) is implicated to be a prognostic factor, although the results are not unanimous. Recently its effect was suggested to be modified by paired box 2 gene product (PAX2).Patients and methodsUsing immunohistochemistry (IHC) AIB1 and PAX2 were investigated in two cohorts of early breast cancer, including systemically untreated premenopausal lymph-node-negative women and pre- and postmenopausal women receiving tamoxifen.ResultsAIB1 scores were available for 490 patients and PAX2 scores were available for 463 patients. High AIB1 was a negative prognostic factor for distant disease-free survival (DDFS, P = 0.02) and overall survival (OS, P < 0.001) in systemically untreated women, while no prognostic effect was seen in the tamoxifen-treated cohort, indicating AIB1 to be a predictor of tamoxifen response. In systemically untreated patients, PAX2 was not a prognostic factor, nor did it modify the effect of AIB1. However, in ER-positive patients receiving tamoxifen, PAX2 appeared to be a positive prognostic factor in premenopausal patients, while a negative factor in postmenopausal. The interaction between the menopausal status and PAX2 was significant (P = 0.01).ConclusionsIn an independent cohort of low-risk premenopausal patients, we validate AIB1 as a negative prognostic factor, indicating AIB1 to be an interesting target for new anti-cancer therapies. The effect of PAX2 warrants further studies.
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- Andersén, Christoffer, 1991-, et al.
(författare)
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Deep learning based digitisation of prostate brachytherapy needles in ultrasound images
- 2020
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Ingår i: Medical physics. - : Wiley-Blackwell Publishing Inc.. - 2473-4209 .- 0094-2405. ; 47:12, s. 6414-6420
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To develop, and evaluate the performance of, a deep learning based 3D convolutional neural network (CNN) artificial intelligence (AI) algorithm aimed at finding needles in ultrasound images used in prostate brachytherapy.METHODS: Transrectal ultrasound (TRUS) image volumes from 1102 treatments were used to create a clinical ground truth (CGT) including 24422 individual needles that had been manually digitised by medical physicists during brachytherapy procedures. A 3D CNN U-net with 128x128x128 TRUS image volumes as input was trained using 17215 needle examples. Predictions of voxels constituting a needle were combined to yield a 3D linear function describing the localisation of each needle in a TRUS volume. Manual and AI digitisations were compared in terms of the root-mean-square distance (RMSD) along each needle, expressed as median and interquartile range (IQR). The method was evaluated on a dataset including 7207 needle examples. A subgroup of the evaluation data set (n=188) was created, where the needles were digitised once more by a medical physicist (G1) trained in brachytherapy. The digitisation procedure was timed.RESULTS: The RMSD between the AI and CGT was 0.55 (IQR: 0.35-0.86) mm. In the smaller subset, the RMSD between AI and CGT was similar (0.52 [IQR: 0.33-0.79] mm) but significantly smaller (p<0.001) than the difference of 0.75 (IQR: 0.49-1.20) mm between AI and G1. The difference between CGT and G1 was 0.80 (IQR: 0.48-1.18) mm, implying that the AI performed as well as the CGT in relation to G1. The mean time needed for human digitisation was 10 min 11 sec, while the time needed for the AI was negligible.CONCLUSIONS: A 3D CNN can be trained to identify needles in TRUS images. The performance of the network was similar to that of a medical physicist trained in brachytherapy. Incorporating a CNN for needle identification can shorten brachytherapy treatment procedures substantially.
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- Andersén, Christoffer, 1991-, et al.
(författare)
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Presults for the aI-Brachy study : Utilizing deep learning for needle reconstruction in prostate brachytherapy
- 2019
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Konferensbidrag (refereegranskat)abstract
- Purpose To develop a deep neural network for automatic reconstruction of needles in ultrasound images depicting the prostate during brachytherapy treatment of prostate cancer.Methods Ultrasound tomographies of the prostate from 907 treatments were used to train the artificial intelligent (AI) algorithm. The image matrices were downsampled to 128x128x128 and were used as in-data when training the AI, a 27 layer convolutional neural network. The needles were identified manually by medical physicists using conventional software. These reconstructions were used as gold standard when training the algorithm. An additional set of examinations were used for validation where the needle reconstructions by the AI were compared to the manual reconstructions. The root mean square deviation (RMSD) of needle position, including the central part (70 slices) of the needle was measured in order to avoid influence from artefacts around the needle tip. The result was also evaluated through visual inspection (see image). The times spent for manual vs. AI reconstruction were compared.Results RMSD for manual vs. AI reconstruction is on average (n=170) 1.18±1.0mm, whereas the difference between two manual operators is 0.02±0.06mm, which suggests that the AI is inferior to manual operators. The visual inspection, however, shows AI to be very accurate in positioning the needles. Manual reconstruction took approximately 11.0 minutes, whereas the time for the trained AI is negligible in comparison. Worth noticing regarding RMSD calculations is that, due to limited image resolution, small values may be under-estimated, hence overestimating the difference between the reconstruction methods.Conclusions The study implies that an AI may reconstruct needles for brachytherapy treatments of prostate cancer. The larger deviations between AI algorithm and manual operators, compared to between human operators appears to disagree with the high accuracy of the visual evaluation. However, visually, manual needle reconstructions appear to deviate more from the ultrasound image than do the AI reconstructions. This discrepancy is mainly caused by manual reconstruction software assuming straight needles, unlike the AI. We conclude that AI gives the opportunity to save a substantial amount of treatment planning time, when the patient is anesthetised. Further studies are needed to determine whether different reconstruction methods impact treatment plans.
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- Andersson, Lars Gustaf, et al.
(författare)
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Folkbildning och avantgarde - tidskriften Filmfront 1953 - 1956
- 2007
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Ingår i: Då och där, här och nu. Festskrift till Ingemar Oscarsson (Absalon - Skrifter utgivna vid Språk- och litteraturcentrum/Litteraturvetenskap). ; , s. 245-257
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- A short account of the Swedish film journal "Filmfront" and its connections to the experimental film movement and individuals like Peter Weiss.
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