| 51. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Effect of selective serotonin reuptake inhibitors use on endocrine therapy adherence and breast cancer mortality : a population-based study
- 2016
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Ingår i: Breast Cancer Research and Treatment. - : Kluwer Academic/Plenum Publishers. - 0167-6806 .- 1573-7217. ; 159:2, s. 293-303
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to investigate whether the concomitant use of selective serotonin reuptake inhibitors (SSRI) with tamoxifen influences the risk of death due to breast cancer, and we also investigated the association between SSRI use and adherence to oral endocrine therapy (ET). We analyzed data from BCBaSe Sweden, which is a database created by the data linkage of Registries from three different regions of Sweden. To investigate the association between ET adherence and SSRI use, we included all women who were diagnosed with non-distant metastatic ER-positive invasive breast cancer from July 2007 to July 2011 and had at least one dispensed prescription of oral tamoxifen or aromatase inhibitor. To investigate the role of concurrent administration of SSRI and tamoxifen on breast cancer prognosis, we performed a nested case-control study. In the adherence cohort, 9104 women were included in the analyses. Women who received SSRI, either before or after breast cancer diagnosis, were at higher risk for low adherence to ET. However, when the overlapping period between SSRI use and ET was >50 %, no excess risk for low adherence was observed. Non-adherence (<80 %) to ET was significantly associated with worse breast cancer survival (OR 4.07; 95 % CI 3.27-5.06). In the case-control study, 445 cases and 11125 controls were included. The concomitant administration of SSRI and tamoxifen did not influence breast cancer survival, neither in short-term (OR 1.41; 95 % CI 0.74-2.68) nor in long-term SSRI users (OR 0.85; 95 % CI 0.35-2.08). Concomitant SSRI and tamoxifen use does not seem to increase risk for death due to breast cancer. Given the positive association between continuing antidepressive pharmacotherapy for a longer period of time and adherence to ET, it is essential to capture and treat depression in breast cancer patients to secure adherence to ET.
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| 52. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Improved survival without increased toxicity with influenza vaccination in cancer patients treated with checkpoint inhibitors
- 2021
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Ingår i: Oncoimmunology. - : Taylor & Francis. - 2162-4011 .- 2162-402X. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- In international guidelines, influenza vaccination is recommended to cancer patients receiving antitumor treatment. Whether this recommendation should include patients treated with the recently introduced and now widely used checkpoint inhibitors (CPIs) is unclear. The immune hyperactivation after vaccination in a patient on CPI treatment may strengthen the antitumor immunity and improve patients´ prognosis. On the other hand, the hyperactivation might increase the risk for immune-related adverse events (IRAEs). Furthermore, there is a risk for decreased antitumor effect by the phenomenon of antigenic competition. Only results from few studies addressing survival have been reported and the results from studies on IRAEs are contradictory. We performed a multi-center retrospective cohort study at three Swedish centers in patients with metastatic cancer. All patients previously not treated with CPIs and who received monotherapy with a PD-1 or PD-L1 blocker between January 1st, 2016 until May 31st, 2019 were included. The most common type of malignancy was melanoma (47.8%) followed by non-small cell lung cancer (31.0%). Statistically significant longer PFS and OS were observed in multivariate analyses at 6-month landmark time in the vaccinated compared to the non-vaccinated group after adjustment for age, gender, comorbidity, performance status, CNS metastasis and line of treatment (p = .041 and 0.028, respectively). Furthermore, the incidence of any IRAE grade was comparable between vaccinated and non-vaccinated group (p = .85). In conclusion, the current study indicates that survival improves with influenza vaccination while not increasing the risk for side effects in cancer patients treated with checkpoint inhibitors. Hence, our results strongly support influenza vaccination in cancer patients receiving checkpoint inhibitors.
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| 53. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Lessons learned from an unsuccessful decentralized clinical trial in Oncology
- 2024
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Ingår i: npj Digital Medicine. - : Springer Nature. - 2398-6352. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Decentralized clinical trials have gained in popularity over the last years due to their advantages related to broadening recruitment strategies and resource saving possibilities. As more clinical trials adopt decentralized strategies, it is essential to share the knowledge about both successful and unsuccessful efforts in the research community. In the present commentary, we explore potential reasons that led to early termination of a decentralized clinical trial in Oncology.
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| 54. |
- Valachis, Antonis, 1984-
(författare)
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Meta-analysis of randomized clinical evidence of chemotherapy, radiotherapy and endocrine therapy in breast cancer
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in females worldwide. Despite the growing body of randomized controlled trials (RCTs) regarding the use of various treatment strategies (chemotherapy, endocrine therapy, radiotherapy) in breast cancer, the efficacy of some strategies remains unclear and questionable. A meta-analysis, by combining the results of all available trials that studied the same question, could help to reduce the level of uncertainty and provide reliable conclusions about the role of various therapeutic choices for breast cancer patients.Objective: The purpose of this thesis was to identify controversial therapeutic strategies in the treatment of breast cancer and to perform, when possible, meta-analyses to find out which of these strategies are valuable in breast cancer therapy. We conducted 7 separate meta-analyses in order to answer to 7 different clinical questions. We choose 7 topics with controversial results in the therapeutic strategy of breast cancer patients, namely the role of bisphosphonates as antitumor therapy and as preventive agents against fractures in adjuvant setting, the risk of osteonecrosis of the jaw (ONJ) with the use of bisphosphonates in adjuvant setting, the use of fulvestrant in advanced breast cancer, the safety of partial breast irradiation (PBI) compared with whole-breast radiotherapy (WBRT), the role of bevacizumab in advanced breast cancer and finally the value of trastuzumab as neoadjuvant therapy in Her2-positive breast cancer patients.Materials and Methods: In all 7 meta-analyses we used the same basic principles of meta-analysis, with some minor but necessary changes in order to fit our methodology to specific aims of each trial. In general, we conducted systematic reviews of all English and non-English medical literature using MEDLINE, the Cochrane Controlled Trials Register and ISI Web of Knowledge. We set no year restriction. The references of all eligible trials were also searched in order to find any potentially eligible trial that it was not identified by our searching algorithm. Abstracts of major meetings were also searched. Eligible studies were identified according to prespecified criteria for each meta-analysis. Data extraction was conducted independently by two investigators. In case of discrepancy, consensus was reached by involvement of a third investigator. When data on the outcome were not available from trials, we contacted the primary investigators of the eligible trials. Data synthesis was perfomed by choosing the appropriate effect size measure (Odds Ratio, Risk Ratio or Hazard Ratio) for each outcome and by combining the results using fixed- or random-effects models.Results: Regarding bisphosphonates in adjuvant setting, pooled results showed no statistical significant differences with the use of bisphosphonates in early breast cancer versus non-use for the overall number of deaths (summary OR, 0.708; 95% CI, 0.482–1.041; p-value =0.079), disease recurrences(summary OR, 0.843; 95% CI, 0.602–1.181; p-value =0.321), and bone metastases (summary OR, 0.925; 95% CI, 0.768–1.114; p-value =0.413). Subgroup analyses for disease recurrences according to the type of bisphosphonate used showed a statistically significant lower risk for disease recurrences with zoledronic acid (6 trials, OR, 0.675; 95% CI, 0.479–0.952; p-value = 0.025). In addition, bisphosphonates did not reduce fracture rate (OR=0.99, 95% CI=0.73–1.34) neither in postmenopausal women (OR=0.82, 95% CI=0.55–1.20) nor in women with breast cancer receiving aromatase inhibitors (OR=0.79, 95% CI=0.53–1.17). Overall, treatment with bisphosphonates was significantly associated with the occurrence of osteonecrosis of the jaw (ONJ) (OR = 3.23, 95% CI = 1.7–8) compared with no use but it was a rare event, occurring in 13 (0.24%) of the 5,312 patients receiving bisphosphonates.Considering fulvestrant, we found no difference between fulvestrant versus other hormonal agents regarding overall survival (HR: 1.047, 95% CI: 0.688–1.592; p-value = 0.830) and time to tumor progression (HR: 0.994, 95% CI: 0.691–1.431; p-value = 0.975).Partial breast irradiation (PBI) did not influence survival (OR 0.912, 95% CI, 0.674–1.234, p-value = 0.550) compared with WBRT but it was found to lead to statistically significant higher risk for developing local recurrences (pooled OR 2.150, 95% CI, 1.396–3.312; p-value = 0.001) and axillary recurrences (pooled OR 3.430, 95% CI, 2.058–5.715; p-value < 0.0001).The combination of bevacizumab and chemotherapy resulted in a statistically significant improvement in progression-free survival compared with chemotherapy alone (HR = 0.70, 95% CI = 0.60–0.82, p-value = 9.3x10-6), especially when bevacizumab was combined with taxanes. However, the pooled HR for overall survival did not show significant advantage for the use of bevacizumab compared to placebo arm (pooled HR = 0.90, 95% CI 0.80–1.03, p-value = 0.119).Finally, the use of trastuzumab as neoadjuvant therapy lead to higher absolute pathologic complete response (pCR) rate (38% in trastuzumab arm in comparison with 21% in no trastuzumab arm) (RR 1.85, 95% CI: 1.39-2.46; p-value < 0.001). Two out of 217 (0.9%) patients in the trastuzumab arms presented congestive heart failure compared with none in the chemotherapy alone arms.Conclusions: The meta-analysis of bisphosphonates in adjuvant breast cancer therapy showed that currently available randomized evidence does not support the hypothesis that using bisphosphonates in adjuvant treatment of early breast cancer alters the natural course of the disease. In addition bisphosphonates do not seem to prevent bone fractures. However, ONJ is a rare event in breast cancer patients treated with adjuvant use of bisphosphonates.Our meta-analysis of fulvestrant suggests that fulvestrant 250 mg is similar to other hormonal agents with respect to efficacy measures with equal or even better tolerability profile compared with other hormonal agents.Our meta-analysis of PBI, despite the fact that it is based on limited randomized evidence, suggests that PBI is a safe treatment modality as it does not seem to jeopardize survival compared with standard WBRT. Nevertheless, the issue of locoregional recurrence needs to be further addressed.The results of the meta-analysis of bevacizumab show that the addition of bevacizumab to chemotherapy offers a statistically significant improvement in progression free survival in patients with metastatic breast cancer but does not benefit overall survival. In addition, clinical significance of this improvement is questionable. As a result, bevacizumab treatment cannot be suggested for treatment of 1st line metastatic breast cancer,Finally, the meta-analysis of trastuzumab as neoadjuvant treatment underscores the beneficial effects of trastuzumab treatment in neoadjuvant regimens among HER2-positive breast cancer patients in terms of pCR. Of interest, no additional cardiotoxicity was documented in the trastuzumab arms.
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| 55. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Overall survival of patients with metastatic breast cancer in Sweden : a nationwide study
- 2022
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 127:4, s. 720-725
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Tidskriftsartikel (refereegranskat)abstract
- Background: Breast cancer is the most common cancer among women in Sweden. Whereas survival for the overall breast cancer population is well-documented, survival of patients with metastatic breast cancer (MBC) is harder to quantify due to the lack of reliable data on disease recurrence in national cancer registers.Methods: This study used machine learning to classify the total MBC population in Sweden diagnosed between 2009 and 2016 using national registers, with the aim to estimate overall survival (OS).Results: The total population consisted of 13,832 patients-2528 (18.3%) had de novo MBC whereas 11,304 (81.7%) were classed as having a recurrent MBC. Median OS for patients with MBC was found to be 29.8 months 95% confidence interval (CI) [28.9, 30.6]. Hormone-receptor (HR)-positive MBC had a median OS of 37.0 months 95% CI [35.9, 38.3] compared to 9.9 months 95% CI [9.1, 11.0] for patients with HR-negative MBC.Conclusion: This study covered the entire MBC population in Sweden during the study time and may serve as a baseline for assessing the effect of new treatment strategies in MBC introduced after the study period.
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| 56. |
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| 57. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Treatment patterns, risk for hospitalization and mortality in older patients with triple negative breast cancer
- 2021
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Ingår i: Journal of Geriatric Oncology. - : Elsevier. - 1879-4068 .- 1879-4076. ; 12:2, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the treatment patterns, potential risk factors for hospitalization within one year from diagnosis, and causes of death in older patients with triple negative breast cancer (TNBC).MATERIALS AND METHODS: We performed a registry-based cohort study using the BCBaSe database which links cases of breast cancer from three Swedish healthcare regions with socioeconomic factors, hospitalizations and causes of death. Women ≥70 years old with non-metastatic TNBC, between 1/12007 and 31/122012 were included (n = 413).RESULTS: In total, 168 patients (40.7%) received chemotherapy after surgery and 123 patients (30.0%) in the whole cohort had at least one hospitalization within one year from diagnosis. The risk of hospitalization overall was increased in the group receiving chemotherapy (Odds Ratio 2.35, 95% Confidence Intervall: 1.30-4.26) mainly due to toxicities. Cumulative incidence of breast cancer mortality was comparable among different age groups (70-74 vs. 75-79 vs. ≥ 80 years old) whereas non-breast cancer mortality was higher in patients ≥80 years old. Stage at diagnosis and comorbidities were independently associated with both breast cancer-specific- and overall mortality whereas age was only associated with overall mortality.CONCLUSIONS: The use of chemotherapy in older patients with TNBC was associated with age, tumor stage, and comorbidities. Chemotherapy use was also associated with increased risk for hospitalization within one year from diagnosis. Although the impact of chemotherapy on mortality was analyzed in a multivariate manner showing neither increased or decreased mortality, no firm conclusion can be drawn due to unmeasured confounders.
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| 58. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Use of classifiers to optimise the identification and characterisation of metastatic breast cancer in a nationwide administrative registry
- 2021
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 60:12, s. 1604-1610
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Tidskriftsartikel (refereegranskat)abstract
- Bakground: The prognosis for patients with metastatic breast cancer (MBC) is substantially worse when compared with patients with earlier stage disease. Therefore, understanding the differences in epidemiology between these two patient groups is important. Studies using population-based cancer registries to identify MBC are hampered by the quality of reporting. Patients are registered once (at time of initial diagnosis); hence only data for patients with de novo MBC are identifiable, whereas data for patients with recurrent MBC are not. This makes accurate estimation of the epidemiology and healthcare utilisation of MBC challenging. This study aimed to investigate whether machine-learning could improve identification of MBC in national health registries.Material and methods: Data for patients with confirmed MBC from a regional breast cancer registry were used to train machine-learning algorithms (or 'classifiers'). The best performing classifier (accuracy 97.3%, positive predictive value 85.1%) was applied to Swedish national registries for 2008 to 2016.Results: Mean yearly MBC incidence was estimated at 14 per 100,000 person-years (with 18% diagnosed de novo and 76% of the total with HR-positive MBC).Conclusion: To our knowledge, this is the first study to use machine learning to identify MBC regardless of stage at diagnosis in health registries covering the entire population of Sweden.
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| 59. |
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| 60. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Use of subcutaneous and intravenous trastuzumab : real-world experience from three hospitals in Sweden
- 2019
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Ingår i: Future Oncology. - : Future Medicine Ltd.. - 1479-6694 .- 1744-8301. ; 15:23, s. 2733-2741
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Tidskriftsartikel (refereegranskat)abstract
- Aim: We aimed to describe the use of subcutaneous (sc.) trastuzumab use in a real-world setting.Patients & methods: This retrospective cohort study evaluated electronic medical records of patients with early breast cancer and trastuzumab use from January 2010 to February 2018 in three hospitals in Sweden.Results: In total, 363 patients received trastuzumab during study period. Of these, 217 (59.8%) patients started treatment with sc. trastuzumab and 146 (40.2%) with intravenous trastuzumab. After sc. trastuzumab approval, use of sc. trastuzumab increased from 70.2% in 2014 to 100% in 2017. Since 2013, 34 of 35 (97.4%) patients who started with intravenous trastuzumab switched to sc. formulation.Conclusion: Trastuzumab sc. quickly became the prevailing formulation for treatment in HER2-positive early breast cancer.
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