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- Andersson, Yvette, et al.
(author)
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Do clinical trials truly mirror their target population? : An external validity analysis of national register versus trial data from the Swedish prospective SENOMIC trial on sentinel node micrometastases in breast cancer
- 2019
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In: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217. ; 177:2, s. 469-475
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Journal article (peer-reviewed)abstract
- Purpose: Increasing evidence suggests that completion axillary lymph node dissection (ALND) may be omitted in breast cancer patients with limited axillary nodal metastases. However, the representativeness of trial participants for the original clinical practice population, and thus, the generalizability of published trials have been questioned. We propose the use of background data from national registers as a means to assess whether trial participants mirror their target population and to strengthen the generalizability and implementation of trial outcomes.Methods: The Swedish prospective SENOMIC trial, omitting a completion ALND in breast cancer patients with sentinel lymph node micrometastases, reached full target accrual in 2017. To assess the generalizability of trial results for the target population, a comparative analysis of trial participants versus cases reported to the Swedish National Breast Cancer Register (NKBC) was performed.Results: Comparing 548 trial participants and 1070 NKBC cases, there were no significant differences in age, tumor characteristics, breast surgery, or adjuvant treatment. Only the mean number of sentinel lymph nodes with micrometastasis per individual was lower in trial participants than in register cases (1.06 vs. 1.09, p=0.037).Conclusions: Patients included in the SENOMIC trial are acceptably representative of the Swedish breast cancer target population. There were some minor divergences between trial participants and the NKBC population, but taking these into consideration, upcoming trial outcomes should be generalizable to breast cancer patients with micrometastases in their sentinel lymph node biopsy.
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| 2. |
- Andersson, Yvette, et al.
(author)
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Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes
- 2018
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In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 171:2, s. 359-369
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Journal article (peer-reviewed)abstract
- Purpose: The clinical significance of lymph node micrometastases and isolated tumor cells (ITCs) in breast cancer is still controversial. After a median follow-up of 52 months, a report from the Swedish Multicenter Cohort Study presented a worse cancer-specific and event-free survival for patients with micrometastases than node-negative individuals, but could not demonstrate a significant difference in overall survival (OS). Due to the tendency of breast cancer to relapse after more than 5-10 years, we now report the long-term survival of the cohort.Methods: Between September 2000 and January 2004, 3355 breast cancer patients were included in a prospective cohort. Sentinel lymph node biopsy was always performed. Patients were classified in four groups according to their overall nodal stage: node negative (N0, 2372), ITCs (113), micrometastases (123), and macrometastases (747). Kaplan-Meier survival estimates and Cox proportional hazard regression models were applied.Results: Median follow-up was 156 months. Ten-year cancer-specific survival and OS were significantly lower in case of micrometastases than in N0 (84.7 vs. 93.5%, p = 0.001, and 75.5 vs. 84.2%, p = 0.046, respectively). In case of macrometastases, corresponding survival rates were 82.8 and 74.3%. Only for those aged less than 50 years, cancer-specific survival and OS were significantly worse in case of ITCs than N0. Patients with micrometastases received less often chemotherapy than those with macrometastases (24.4 vs. 53.9%).Conclusions: Lymph node micrometastases in breast cancer have a prognostic significance. This study demonstrates a similar survival for patients with micrometastases and those with macrometastases, possibly due to systemic undertreatment.
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| 4. |
- de Boniface, J., et al.
(author)
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The generalisability of randomised clinical trials: an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer
- 2020
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In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 180:1, s. 167-176
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Journal article (peer-reviewed)abstract
- Purpose None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC). Methods In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1-T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are eligible interventions. Data from NKBC were extracted for the years 2016 and 2017, and patient and tumour characteristics compared with Swedish trial participants from the same years. Results Overall, 306 NKBC cases from non-participating and 847 NKBC cases from participating sites (excluding SENOMAC participants) were compared with 463 SENOMAC trial participants. Patients belonging to the middle age groups (p = 0.015), with smaller tumours (p = 0.013) treated by breast-conserving therapy (50.3 versus 47.1 versus 65.2%, p < 0.001) and less nodal tumour burden (only 1 macrometastasis in 78.8 versus 79.9 versus 87.3%, p = 0.001) were over-represented in the trial population. Time trends indicated, however, that differences may be mitigated over time. Conclusions This interim external validity analysis specifically addresses selection mechanisms during an ongoing trial, potentially increasing generalisability by the time full accrual is reached. Similar validity checks should be an integral part of prospective clinical trials. Trial registration: NCT 02240472, retrospective registration date September 14, 2015 after trial initiation on January 31, 2015
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