| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Ring, A., et al.
(författare)
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Bridging The Age Gap: observational cohort study of effects of chemotherapy and trastuzumab on recurrence, survival and quality of life in older women with early breast cancer
- 2021
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 125, s. 209-219
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy. Methods: A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage. Results: Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19–0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20–0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08–0.49];BCSS: HR 0.12 [95% CI 0.03–0.44]).Transient negative quality-of-life impacts were observed. Conclusions: Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient. Trial Registration: ISRCTN 46099296. © 2021, The Author(s).
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| 3. |
- Simpson, J., et al.
(författare)
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Evolution of structure and shapes in Er 158 to ultrahigh spin
- 2023
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Ingår i: Physical Review C. - 2469-9985. ; 107:5
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Tidskriftsartikel (refereegranskat)abstract
- The level structure of Er158 has been studied using the Gammasphere spectrometer via the Cd114(Ca48,4n) reaction at 215 MeV with both thin (self-supporting) and thick (backed) targets. The level scheme has been considerably extended with more than 200 new transitions and six new rotational structures, including two strongly coupled high-K bands. Configuration assignments for the new structures are based on their observed alignments, B(M1)/B(E2) ratios of reduced transition probabilities, excitation energies, and comparisons with neighboring nuclei and theoretical calculations. With increasing angular momentum, this nucleus exhibits Coriolis-induced alignments of both neutrons and protons before it then undergoes a rotation-induced transition from near-prolate collective rotation to a noncollective oblate configuration. This transition occurs via the mechanism of band termination around spin 45ħ in three rotational structures. Two distinct lifetime branches, consistent with the crossing of a collective "fast"rotational structure by an energetically favored "slow"terminating sequence, are confirmed for the positive-parity states, and similar behavior is established in the negative-parity states. Weak-intensity, high-energy transitions are observed to feed into the terminating states. At the highest spins, three collective bands with high dynamic moments of inertia and large quadrupole moments were identified. These bands are interpreted as triaxial strongly deformed structures and mark a return to collectivity at ultrahigh spin.
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| 4. |
- Wyld, L., et al.
(författare)
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Improving outcomes for women aged 70 years or above with early breast cancer: Research programme including a cluster RCT
- 2022
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Ingår i: Programme Grants for Applied Research. - 2050-4322. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: In breast cancer management, age-related practice variation is widespread, with older women having lower rates of surgery and chemotherapy than younger women, based on the premise of reduced treatment tolerance and benefit. This may contribute to inferior outcomes. There are currently no age-and fitness-stratified guidelines on which to base treatment recommendations. Aim: We aimed to optimise treatment choice and outcomes for older women (aged > 70 years) with operable breast cancer. Objectives: Our objectives were to (1) determine the age, comorbidity, frailty, disease stage and biology thresholds for endocrine therapy alone versus surgery plus adjuvant endocrine therapy, or adjuvant chemotherapy versus no chemotherapy, for older women with breast cancer; (2) optimise survival outcomes for older women by improving the quality of treatment decision-making; (3) develop and evaluate a decision support intervention to enhance shared decision-making; and (4) determine the degree and causes of treatment variation between UK breast units. Design: A prospective cohort study was used to determine age and fitness thresholds for treatment allocation. Mixed-methods research was used to determine the information needs of older women to develop a decision support intervention. A cluster-randomised trial was used to evaluate the impact of this decision support intervention on treatment choices and outcomes. Health economic analysis was used to evaluate the cost-benefit ratio of different treatment strategies according to age and fitness criteria. A mixed-methods study was used to determine the degree and causes of variation in treatment allocation. Main outcome measures: The main outcome measures were enhanced age-and fitness-specific decision support leading to improved quality-of-life outcomes in older women (aged > 70 years) with early breast cancer. Results: (1) Cohort study: The study recruited 3416 UK women aged > 70 years (median age 77 years). Follow-up was 52 months. (a) The surgery plus adjuvant endocrine therapy versus endocrine therapy alone comparison: 2854 out of 3416 (88%) women had oestrogen-receptor-positive breast cancer, 2354 of whom received surgery plus adjuvant endocrine therapy and 500 received endocrine therapy alone. Patients treated with endocrine therapy alone were older and frailer than patients treated with surgery plus adjuvant endocrine therapy. Unmatched overall survival and breast-cancer-specific survival were higher in the surgery plus adjuvant endocrine therapy group (overall survival: Hazard ratio 0.27, 95% confidence interval 0.23 to 0.33; p < 0.001; breast-cancer-specific survival: Hazard ratio 0.41, 95% confidence interval 0.29 to 0.58; p < 0.001) than in the endocrine therapy alone group. In matched analysis, surgery plus adjuvant endocrine therapy was still associated with better overall survival (hazard ratio 0.72, 95% confidence interval 0.53 to 0.98; p = 0.04) than endocrine therapy alone, but not with better breast-cancer-specific survival (hazard ratio 0.74, 95% confidence interval 0.40 to 1.37; p = 0.34) or progression-free-survival (hazard ratio 1.11, 95% confidence interval 0.55 to 2.26; p = 0.78). (b) The adjuvant chemotherapy versus no chemotherapy comparison: 2811 out of 3416 (82%) women received surgery plus adjuvant endocrine therapy, of whom 1520 (54%) had high-recurrence-risk breast cancer [grade 3, node positive, oestrogen receptor negative or human epidermal growth factor receptor-2 positive, or a high Oncotype DX® (Genomic Health, Inc., Redwood City, CA, USA) score of > 25]. In this high-risk population, there were no differences according to adjuvant chemotherapy use in overall survival or breast-cancer-specific survival after propensity matching. Adjuvant chemotherapy was associated with a lower risk of metastatic recurrence than no chemotherapy in the unmatched (adjusted hazard ratio 0.36, 95% confidence interval 0.19 to 0.68; p = 0.002) and propensity-matched patients (adjusted hazard ratio 0.43, 95% confidence interval 0.20 to 0.92; p = 0.03). Adjuva t chemotherapy improved the overall survival and breast-cancer-specific survival of patients with oestrogen-receptor-negative disease. (2) Mixed-methods research to develop a decision support intervention: An iterative process was used to develop two decision support interventions (each comprising a brief decision aid, a booklet and an online tool) specifically for older women facing treatment choices (endocrine therapy alone or surgery plus adjuvant endocrine therapy, and adjuvant chemotherapy or no chemotherapy) using several evidence sources (expert opinion, literature and patient interviews). The online tool was based on models developed using registry data from 23,842 patients and validated on an external data set of 14,526 patients. Mortality rates at 2 and 5 years differed by < 1% between predicted and observed values. (3) Cluster-randomised clinical trial of decision support tools: 46 UK breast units were randomised (intervention, n = 21; usual care, n = 25), recruiting 1339 women (intervention, n = 670; usual care, n = 669). There was no significant difference in global quality of life at 6 months post baseline (difference-0.20, 95% confidence interval-2.7 to 2.3; p = 0.90). In women offered a choice of endocrine therapy alone or surgery plus adjuvant endocrine therapy, knowledge about treatments was greater in the intervention arm than the usual care arm (94% vs. 74%; p = 0.003). Treatment choice was altered, with higher rates of endocrine therapy alone than of surgery in the intervention arm. Similarly, chemotherapy rates were lower in the intervention arm (endocrine therapy alone rate: Intervention sites 21% vs. usual-care sites 15%, difference 5.5%, 95% confidence interval 1.1% to 10.0%; p = 0.02; adjuvant chemotherapy rate: Intervention sites 10% vs. usual-care site 15%, difference 4.5%, 95% confidence interval 0.0% to 8.0%; p = 0.013). Survival was similar in both arms. (4) Health economic analysis: A probabilistic economic model was developed using registry and cohort study data. For most health and fitness strata, surgery plus adjuvant endocrine therapy had lower costs and returned more quality-adjusted life-years than endocrine therapy alone. However, for some women aged > 90 years, surgery plus adjuvant endocrine therapy was no longer cost-effective and generated fewer quality-adjusted life-years than endocrine therapy alone. The incremental benefit of surgery plus adjuvant endocrine therapy reduced with age and comorbidities. (5) Variation in practice: analysis of rates of surgery plus adjuvant endocrine therapy or endocrine therapy alone between the 56 breast units in the cohort study demonstrated significant variation in rates of endocrine therapy alone that persisted after adjustment for age, fitness and stage. Clinician preference was an important determinant of treatment choice. Conclusions: This study demonstrates that, for older women with oestrogen-receptor-positive breast cancer, there is a cohort of women with a life expectancy of < 4 years for whom surgery plus adjuvant endocrine therapy may offer little benefit and simply have a negative impact on quality of life. The Age Gap decision tool may help make this shared decision. Similarly, although adjuvant chemotherapy offers little benefit and has a negative impact on quality of life for the majority of older women with oestrogen-receptor-positive breast cancer, for women with oestrogen-receptor-negative breast cancer, adjuvant chemotherapy is beneficial. The negative impacts of adjuvant chemotherapy on quality of life, although significant, are transient. This implies that, for the majority of fitter women aged > 70 years, standard care should be offered. Limitations: As with any observational study, despite detailed propensity score matching, residual bias cannot be excluded. Follow-up was at median 52 months for the cohort analysis. Longer-term follow-up will be required to validate these findings owing to the slow time course of oestrogen-receptor-positive breast cancer. Future work: The online algorithm is now available (URL: Https://ag gap.shef.ac.uk/; accessed May 2022). There are plans to validate the tool and incorprate quality-of-life and 10-year survival outcomes.
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| 5. |
- Holmes, G. R., et al.
(författare)
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Cost-Effectiveness Modeling of Surgery Plus Adjuvant Endocrine Therapy Versus Primary Endocrine Therapy Alone in UK Women Aged 70 and Over With Early Breast Cancer
- 2021
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Ingår i: Value in Health. - : Elsevier BV. - 1098-3015. ; 24:6, s. 770-779
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Approximately 20% of UK women aged 70+ with early breast cancer receive primary endocrine therapy (PET) instead of surgery. PET reduces surgical morbidity but with some survival decrement. To complement and utilize a treatment dependent prognostic model, we investigated the cost-effectiveness of surgery plus adjuvant therapies versus PET for women with varying health and fitness, identifying subgroups for which each treatment is cost-effective. Methods: Survival outcomes from a statistical model, and published data on recurrence, were combined with data from a large, multicenter, prospective cohort study of over 3400 UK women aged 70+ with early breast cancer and median 52-month follow-up, to populate a probabilistic economic model. This model evaluated the cost-effectiveness of surgery plus adjuvant therapies relative to PET for 24 illustrative subgroups: Age {70, 80, 90} × Nodal status {FALSE (F), TRUE (T)} × Comorbidity score {0, 1, 2, 3+}. Results: For a 70-year-old with no lymph node involvement and no comorbidities (70, F, 0), surgery plus adjuvant therapies was cheaper and more effective than PET. For other subgroups, surgery plus adjuvant therapies was more effective but more expensive. Surgery plus adjuvant therapies was not cost-effective for 4 of the 24 subgroups: (90, F, 2), (90, F, 3), (90, T, 2), (90, T, 3). Conclusion: From a UK perspective, surgery plus adjuvant therapies is clinically effective and cost-effective for most women aged 70+ with early breast cancer. Cost-effectiveness reduces with age and comorbidities, and for women over 90 with multiple comorbidities, there is little cost benefit and a negative impact on quality of life. © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research
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| 6. |
- Morgan, J. L., et al.
(författare)
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Observational cohort study to determine the degree and causes of variation in the rate of surgery or primary endocrine therapy in older women with operable breast cancer
- 2021
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983. ; 47:2, s. 261-268
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the UK there is variation in the treatment of older women with breast cancer, with up to 40% receiving primary endocrine therapy (PET), which is associated with inferior survival. Case mix and patient choice may explain some variation in practice but clinician preference may also be important. Methods: A multicentre prospective cohort study of women aged >70 with operable breast cancer. Patient characteristics (health status, age, tumour characteristics, treatment allocation and decision-making preference) were analysed to identify whether treatment variation persisted following case-mix adjustment. Expected case-mix adjusted surgery rates were derived by logistic regression using the variables age, co-morbidity, tumour stage and grade. Concordance between patients’ preferred and actual decision-making style was assessed and associations between age, treatment and decision-making style calculated. Results: Women (median age 77, range 70–102) were recruited from 56 UK breast units between 2013 and 2018. Of 2854/3369 eligible women with oestrogen receptor positive breast cancer, 2354 were treated with surgery and 500 with PET. Unadjusted surgery rates varied between hospitals, with 23/56 units falling outside the 95% confidence intervals on funnel plots. Adjusting for case mix reduced, but did not eliminate, this variation between hospitals (10/56 units had practice outside the 95% confidence intervals). Patients treated with PET had more patient-centred decisions compared to surgical patients (42.2% vs 28.4%, p < 0.001). Conclusions: This study demonstrates variation in treatment selection thresholds for older women with breast cancer. Health stratified guidelines on thresholds for PET would help reduce variation, although patient preference should still be respected. © 2020 The Authors
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| 7. |
- Lewis, M. C., et al.
(författare)
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Decay of a 19(-) isomeric state in Lu-156
- 2018
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 98:2
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Tidskriftsartikel (refereegranskat)abstract
- A multiparticle spin-trap isomeric state having a half-life of 179(4) ns and lying 2601 keV above the yrast 10(+) state in Lu-156 has been discovered. The Lu-156 nuclei were produced by bombarding isotopically enriched Cd-106 targets with beams of Ni-58 ions, separated in flight using the gas-filled separator RITU and their decays were measured using the GREAT spectrometer. Analysis of the main decay path that populates yrast states observed previously suggests a spin-parity assignment of 19(-) for the isomeric state, which is consistent with isomeric states identified in the N = 85 isotones. Comparison with other decay paths in Lu-156 indicates that the [pi h(11/)(2)(-1) circle times nu h(9/2)]10(+) state at the bottom of the yrast sequence is likely to be the a-decaying isomeric state, with the [pi h(11/)(2)(-1) circle times nu f(7/2)]9(+) state lying 62 keV above it. The relative ordering of the lowest-lying 9(+) and 10(+) states is inverted in Lu-156 compared with its odd-odd isotones.
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| 8. |
- Parr, E., et al.
(författare)
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Fine structure in the alpha decay of high-spin isomers in Lu-155 and Hf-156
- 2018
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 98:2
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Tidskriftsartikel (refereegranskat)abstract
- Fine structure in the a decay of high-spin isomers in Lu-155( 25/2(-)) and Hf-156(8(+))has been studied for the first time using alpha gamma- coincidence analysis. Three new a decays from Lu-155(25/2(-)) and two from Hf-156(8(+)) have been identified, populating seniority s > 1 states in the N = 82 nuclei Tm-151 and Yb-152, respectively. The reduced hindrance factors of the a decays support the previous configuration assignments of the populated states. This is the first observation of states with excitation energy greater than 1.5 MeV being populated following a decay in nuclei outside of the Pb-208 region.
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| 9. |
- Hartley, D. J., et al.
(författare)
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Persistence of collective behavior at high spin in the N=88 nucleus Tb-153
- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:5
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in the N = 88 nucleus Tb-153 were observed up to spin similar to 40 in an experiment utilizing the Gammasphere array. The Tb-153 states were populated in a weak alpha 4n evaporation channel of the Cl-37 + Sn-124 reaction. Two previously known sequences were extended to higher spins, and a new decoupled structure was identified. The pi h(11/2) band was observed in the spin region where other N = 88 isotopes exhibit effects of prolate to oblate shape changes leading to band termination along the yrast line, whereas Tb-153 displays a persistent collective behavior. However, minor perturbations of the very highest state in both signatures of this h(11/2) band are observed, which perhaps signal the start of the transition towards band termination.
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| 10. |
- Mustafa, M., et al.
(författare)
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Diverse collective excitations in Er-159 up to high spin
- 2011
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 84:5
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Tidskriftsartikel (refereegranskat)abstract
- A spectroscopic investigation of the gamma decays from excited states in Er-159 has been performed to study the changing structural properties exhibited as ultrahigh spins (I > 60 (h) over bar) are approached. The nucleus of Er-159 was populated by the reaction Cd-116(Ca-48, 5n gamma) at a beam energy of 215 MeV, and the resulting gamma decays were studied using the Gammasphere spectrometer. New rotational bands and extensions to existing sequences were observed, which are discussed in terms of the cranked shell model, revealing a diverse range of quasiparticle configurations. At spins around 50 (h) over bar, there is evidence for a change from dominant prolate collective motion at the yrast line to oblate non-collective structures via the mechanism of band termination. A possible strongly deformed triaxial band occurs at these high spins, which indicates collectivity beyond 50 (h) over bar. The high-spin data are interpreted within the framework of cranked Nilsson-Strutinsky calculations.
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