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OBJECTIVE: The objective of this study is to determine the prevalence and predictors of sickness absence (SA) and disability pension (DP) in women with metastatic breast cancer (mBC). METHODS: Data were obtained from Swedish registers concerning 1,240 adult women diagnosed 1997-2011 with mBC, from 1 year before (y-1) to 2 (y1) and 2 (y2) years after diagnosis. SA and DP prevalence was calculated. Odds ratios (AOR) were determined for factors associated with using long-term (SA > 180 days or DP > 0 days) sickness benefits. RESULTS: Prevalence of SA and DP was 56.0% and 24.8% during y-1, 69.9% and 28.9% during y1, and 64.0% and 34.7% during y2, respectively. Odds of using long-term sickness benefits were higher y1 and y2 in patients using long-term sickness benefits the year before diagnosis (AOR = 3.82, 95% CI 2.91-5.02; AOR = 4.31, 95% CI 2.96-6.29, respectively) and y2 in patients with mBC diagnosis 1997-2000 (AOR = 1.84, 95% CI 1.10-3.08) and using long-term sickness benefits the year after diagnosis (AOR = 22.10, 95% CI 14.33-34.22). CONCLUSIONS: The prevalence of sickness benefit utilisation was high and increased after mBC diagnosis, particularly for patients using long-term sickness benefits prior to diagnosis. Additional study is needed to determine factors that might reduce the need for sickness benefits and enhance work ability in these patients.
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Neoplasias da Mama , Pessoas com Deficiência , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Estudos de Coortes , Feminino , Humanos , Pensões , Fatores de Risco , Licença Médica , Suécia/epidemiologiaRESUMO
OBJECTIVE: We aimed to determine the longitudinal prevalence and the predictors of sickness absence (SA) and disability pension (DP) in breast cancer (BC) women who eventually developed relapse. METHODS: A total of 1293 BC women, who were ages 20-63 years, diagnosed between 1996 and 2011 and by 2016 had all developed relapse, were identified in Swedish registers and were followed from two years before to five years after their primary diagnosis, while they were relapse-free. Annual prevalence of SA and DP was calculated. Logistic regression was used to estimate adjusted odds ratios (AOR) for long-term SA (>30 days) at one (y1) and three (y3) years post-diagnosis. RESULTS: Prevalence of long-term SA was 68.1% in y1 and 16.3% in y5. Prevalence of DP progressively increased from 16.3% in y1 to 29.0% in y5. Predictors of long-term SA included age <50 years (y1:AOR = 1.79 [1.39-2.29]), TNM stage III (y1:AOR = 1.54 [1.03-2.31]; y3:AOR = 2.21 [1.32-3.72]), metastasis (y1:AOR = 1.64 [1.26-2.12]; y3:AOR = 1.51 [1.05-2.18]), comorbidity (y1:AOR = 2.41 [1.55-3.76]; y3 AOR = 4.62 [2.49-8.57]) and any combination of radiotherapy, chemotherapy and hormonal therapy (y1:AOR = 2.05-5.71). CONCLUSION: Among BC women who later developed relapse, those who had higher stages of BC, had comorbidity and received neoadjuvant and/or adjuvant therapy were at significantly higher risk of needing long-term SA after their diagnosis.
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Neoplasias da Mama , Pessoas com Deficiência , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Comorbidade , Feminino , Humanos , Recém-Nascido , Pensões , Recidiva , Fatores de Risco , Licença Médica , Suécia/epidemiologiaRESUMO
Anaplastic and poorly differentiated thyroid cancer (ATC, PDTC) are rare and highly aggressive tumors that historically have been associated with a short life expectancy and low chance of cure. Molecular pathology and the introduction of highly effective targeted drugs have revolutionized the possibilities of management of patients with ATC and PDTC, with BRAF and MEK inhibitors as the most prominent example. Here we provide updated recommendations regarding diagnostics and management, including primary surgical management and targeted therapies based on specific molecular pathological findings.
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Terapia de Alvo Molecular , Proteínas Proto-Oncogênicas B-raf , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/diagnóstico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/patologia , Carcinoma Anaplásico da Tireoide/genética , Carcinoma Anaplásico da Tireoide/diagnóstico , Inibidores de Proteínas Quinases/uso terapêutico , Antineoplásicos/uso terapêuticoRESUMO
INTRODUCTION: Cancer is a leading cause of morbidity and mortality worldwide, and coordinated research efforts are vital to improve global outcomes. Clinical or translational research is usually planned, coordinated and executed by clinical researchers. With this survey we aimed to identify the main hurdles in front of young clinical investigators in oncology. METHODS AND MATERIALS: An anonymized survey was distributed using social media between April and November 2022. Target population were health-care professionals in the field of oncology - physicians, nurses and researchers. We divided participants according to working experience (<40 vs. >40 years of age) and country of practice (Europeans vs. non-Europeans). RESULTS: We received 121 responses from participants practicing in 36 countries. Eighty-seven (72%) of the participants were under 40 years. Eighty-nine (74%) were from European countries and thirty-two (26%) were from non-European. Experienced and European professionals were more likely to be involved in all different aspects of clinical trials. The main source of funding - independently of geographic location - were industry grants. Investigators out of Europe have less participation in international grants. Over 50% of participants dedicate time for clinical research from their personal time and are not paid for it. Almost 50% of investigators don't have access to an experienced mentor in their institution. CONCLUSION: The majority of respondents to our survey are active clinical researchers. Our data indicate that access to education and training as well as possibilities for appropriate networking, and specifically lack of mentorship, are key limiting factors in developing clinical research by healthcare professionals.
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Oncologia , Pesquisadores , Humanos , Inquéritos e Questionários , Adulto , Pesquisa Biomédica , Feminino , Masculino , Europa (Continente) , Apoio à Pesquisa como Assunto , Pessoa de Meia-Idade , MentoresRESUMO
Human epidermal growth factor receptor 2 (HER2) is a major prognostic and predictive marker overexpressed in 15-20% of breast cancers. The diagnostic reference standard for selecting patients for HER2-targeted therapy is based on the analysis of tumor biopsies. Previously patients were defined as HER2-positive or -negative; however, with the approval of novel treatment options, specifically the antibody-drug conjugate trastuzumab deruxtecan, many breast cancer patients with tumors expressing low levels of HER2 have become eligible for HER2-targeted therapy. Such patients will need to be reliably identified by suitable diagnostic methods. Biopsy-based diagnostics are invasive, and repeat biopsies are not always feasible. They cannot visualize the heterogeneity of HER2 expression, leading to a substantial number of misdiagnosed patients. An alternative and highly accurate diagnostic method is molecular imaging with radiotracers. In the case of HER2, various studies demonstrate the clinical utility and feasibility of such approaches. Radiotracers based on Affibody® molecules, small, engineered affinity proteins with a size of ~6.5 kDa, are clinically validated molecules with favorable characteristics for imaging. In this article, we summarize the HER2-targeted therapeutic landscape, describe our experience with imaging diagnostics for HER2, and review the currently available clinical data on HER2-Affibody-based molecular imaging as a novel diagnostic tool in breast cancer and beyond.
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Patients with HER2-low metastatic breast cancer (mBC), defined as an immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification, may benefit from HER2 antibody-drug conjugates. Identifying suitable candidates is a clinical challenge because of spatial and temporal heterogeneity in HER2 expression and discrepancies in pathologic reporting. We aimed to investigate the feasibility and safety of HER2-specific PET imaging with [68Ga]Ga-ABY-025 for visualization of HER2-low mBC. Methods: A prospective pilot study was done with 10 patients who had HER2-low mBC, as part of a phase 2 basket imaging study with [68Ga]Ga-ABY-025 in HER2-expressing solid tumors. Patients were recruited at the Breast Clinic at the Karolinska University Hospital, Stockholm, Sweden. PET/CT images were acquired 3 h after injection of 200 MBq of [68Ga]Ga-ABY-025. The SUVmax was used to quantify tracer uptake. Ultrasound-guided tumor biopsies were guided by results from the HER2 PET. The main outcome-the safety and feasibility of HER2 PET in patients with HER2-low mBC, measured the occurrence of possible procedure-related adverse events. Results: Ten patients with HER2-low mBC underwent [68Ga]Ga-ABY-025 PET/CT with paired tumor biopsies. No adverse events occurred. In all patients, [68Ga]Ga-ABY-025-avid lesions with substantial intra- and interindividual heterogeneity in tracer uptake were noted. In 8 of 10 patients with ABY-025-avid lesions, the HER2-low status of the corresponding lesions was confirmed by IHC or in situ hybridization. Two patients had an IHC score of 0 in the tumor biopsies:1 in a cutaneous lesion with a low SUVmax and 1 in a liver metastasis with a high SUVmax but a "cold" core. Conclusion: The visualization of HER2-low mBC with [68Ga]Ga-ABY-025 PET/CT was feasible and safe. Areas of tracer uptake showed varying levels of HER2 expression on IHC. The observed intra- and interindividual heterogeneity in [68Ga]Ga-ABY-025 uptake suggested that HER2 PET might be used as a tool for the noninvasive assessment of disease heterogeneity and has the potential to identify patients in whom HER2-targeted drugs can have a clinical benefit.
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Neoplasias da Mama , Fragmentos de Peptídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptor ErbB-2 , Proteína Estafilocócica A , Humanos , Projetos Piloto , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Feminino , Pessoa de Meia-Idade , Idoso , Radioisótopos de Gálio , Adulto , Estudos Prospectivos , Compostos Radiofarmacêuticos , Tomografia por Emissão de PósitronsRESUMO
Physical exercise both during and after curative cancer treatment has been shown to reduce side effects. Evidence in the metastatic cancer setting is scarce, and interventions that improve health-related quality of life (HRQOL) are much needed for patients with metastatic breast cancer (MBC). The multinational randomized controlled PREFERABLE-EFFECT trial assessed the effects of exercise on fatigue and HRQOL in patients with MBC. In total, 357 patients with MBC and a life expectancy of ≥6 months but without unstable bone metastases were recruited at eight study centers across five European countries and Australia. Participants were randomly assigned (1:1) to usual care (control group, n = 179) or a 9-month supervised exercise program (exercise group, n = 178). Intervention effects on physical fatigue (European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-FA12 scale) and HRQOL (EORTC QLQ-C30 summary score) were determined by comparing the change from baseline to 3, 6 (primary timepoint) and 9 months between groups using mixed models for repeated measures, adjusted for baseline values of the outcome, line of treatment (first or second versus third or higher) and study center. Exercise resulted in significant positive effects on both primary outcomes. Physical fatigue was significantly lower (-5.3 (95% confidence interval (CI), -10.0 to -0.6), Bonferroni-Holm-adjusted P = 0.027; Cohen's effect size, 0.22) and HRQOL significantly higher (4.8 (95% CI, 2.2-7.4), Bonferroni-Holm-adjusted P = 0.0003; effect size, 0.33) in the exercise group than in the control group at 6 months. Two serious adverse events occurred (that is, fractures), but both were not related to bone metastases. These results demonstrate that supervised exercise has positive effects on physical fatigue and HRQOL in patients with MBC and should be recommended as part of supportive care.ClinicalTrials.gov Identifier: NCT04120298 .
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BACKGROUND: Regular exercise has been shown to have beneficial health effects in cancer survivors, including improving quality of life and other important health outcomes. However, providing people with cancer with easily accessible, high-quality exercise support and programs is a challenge. Therefore, there is a need to develop easily accessible exercise programs that draw upon the current evidence. Supervised, distance-based exercise programs have the benefit of reaching out to many people whilst providing the support of an exercise professional. The aim of the EX-MED Cancer Sweden trial is to examine the effectiveness of a supervised, distance-based exercise program, in people previously treated for breast, prostate, or colorectal cancer, on health-related quality of life (HRQoL), as well as other physiological and patient-reported health outcomes. METHODS: The EX-MED Cancer Sweden trial is a prospective randomised controlled trial including 200 people that have completed curative treatment for breast, prostate, or colorectal cancer. Participants are randomly allocated to an exercise group or a routine care control group. The exercise group will participate in a supervised, distanced-based exercise program delivered by a personal trainer who has undertaken specialised exercise oncology education modules. The intervention consists of a combination of resistance and aerobic exercises with participants completing two 60-min sessions per week for 12 weeks. The primary outcome is HRQoL (EORTC QLQ-C30) assessed at baseline, 3- (end of intervention and primary endpoint) and 6-months post-baseline. Secondary outcomes are physiological (cardiorespiratory fitness, muscle strength, physical function, body composition) and patient-reported outcomes (cancer-related symptoms, fatigue, self-reported physical activity), and self-efficacy of exercise. Furthermore, the trial will explore and describe the experiences of participation in the exercise intervention. DISCUSSION: The EX-MED Cancer Sweden trial will provide evidence regarding the effectiveness of a supervised, distance-based exercise program for survivors of breast, prostate, and colorectal cancer. If successful, it will contribute to the implementation of flexible and effective exercise programs as part of the standard of care for people following cancer treatment, which is likely to contribute to a reduction in the burden of cancer on the individual, health care system and society. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT05064670. Registered on October 1, 2021.
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Neoplasias Colorretais , Próstata , Masculino , Humanos , Qualidade de Vida , Estudos Prospectivos , Suécia , Exercício Físico , Terapia por Exercício/efeitos adversos , Terapia por Exercício/métodos , Neoplasias Colorretais/terapia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Expanding therapeutic possibilities have improved disease-related prospects for breast cancer patients. Pathological analysis on a tumor biopsy is the current reference standard biomarker used to select for treatment with targeted anticancer drugs. This method has, however, several limitations, related to intra- and intertumoral as well as spatial heterogeneity in receptor expression as well as the need to perform invasive procedures that are not always technically feasible. MAIN BODY: In this narrative review, we focus on the current role of molecular imaging with contemporary radiotracers for positron emission tomography (PET) in breast cancer. We provide an overview of diagnostic radiotracers that represent treatment targets, such as programmed death ligand 1, human epidermal growth factor receptor 2, polyadenosine diphosphate-ribose polymerase and estrogen receptor, and discuss developments in therapeutic radionuclides for breast cancer management. CONCLUSION: Imaging of treatment targets with PET tracers may provide a more reliable precision medicine tool to find the right treatment for the right patient at the right time. In addition to visualization of the target of treatment, theranostic trials with alpha- or beta-emitting isotopes provide a future treatment option for patients with metastatic breast cancer.
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BACKGROUND: The Affibody molecule, ABY-025, has demonstrated utility to detect human epidermal growth factor receptor 2 (HER2) in vivo, either radiolabelled with indium-111 (111In) or gallium-68 (68Ga). Using the latter, 68Ga, is preferred due to its use in positron emission tomography with superior resolution and quantifying capabilities in the clinical setting compared to 111In. For an ongoing phase II study (NCT05619016) evaluating ABY-025 for detecting HER2-low lesions and selection of patients for HER2-targeted treatment, the aim was to optimize an automated and cGMP-compliant radiosynthesis of [68Ga]Ga-ABY-025. [68Ga]Ga-ABY-025 was produced on a synthesis module, Modular-Lab PharmTracer (Eckert & Ziegler), commonly used for 68Ga-labelings. The radiotracer has previously been radiolabeled on this module, but to streamline the production, the method was optimized. Steps requiring manual interactions to the radiolabeling procedure were minimized including a convenient and automated pre-concentration of the 68Ga-eluate and a simplified automated final formulation procedure. Every part of the radiopharmaceutical production was carefully developed to gain robustness and to avoid any operator bound variations to the manufacturing. The optimized production method was successfully applied for 68Ga-labeling of another radiotracer, verifying its versatility as a universal and robust method for radiosynthesis of Affibody-based peptides. RESULTS: A simplified and optimized automated cGMP-compliant radiosynthesis method of [68Ga]Ga-ABY-025 was developed. With a decay corrected radiochemical yield of 44 ± 2%, a radiochemical purity (RCP) of 98 ± 1%, and with an RCP stability of 98 ± 1% at 2 h after production, the method was found highly reproducible. The production method also showed comparable results when implemented for radiolabeling another similar peptide. CONCLUSION: The improvements made for the radiosynthesis of [68Ga]Ga-ABY-025, including introducing a pre-concentration of the 68Ga-eluate, aimed to utilize the full potential of the 68Ge/68Ga generator radioactivity output, thereby reducing radioactivity wastage. Furthermore, reducing the number of manually performed preparative steps prior to the radiosynthesis, not only minimized the risk of potential human/operator errors but also enhanced the process' robustness. The successful application of this optimized radiosynthesis method to another similar peptide underscores its versatility, suggesting that our method can be adopted for 68Ga-labeling radiotracers based on Affibody molecules in general. TRIAL REGISTRATION: NCT, NCT05619016, Registered 7 November 2022, https://clinicaltrials.gov/study/NCT05619016?term=HER2&cond=ABY025&rank=1.
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Pharmacogenomics is an emerging field in oncology, one that could provide valuable input on identifying patients with inherent risk of toxicity, thus allowing for treatment tailoring and personalization on the basis of the clinical and genetic characteristics of a patient. Cardiotoxicity is a well-known side effect of anthracyclines and anti-HER2 agents, although at a much lower incidence for the latter. Data on single-nucleotide polymorphisms related to cardiotoxicity are emerging but are still scarce, mostly being of retrospective character and heterogeneous. A literature review was performed, aiming to describe current knowledge in pharmacogenomics and prediction of cardiotoxicity related to breast cancer systemic therapies and radiotherapies. Most available data regard genes encoding various enzymes related to anthracycline metabolism and HER2 polymorphisms. The available data are presented, together with the challenges and open questions in the field.
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Enhanced screening and efficient cancer treatments have led to a growing number of cancer survivors. In Sweden over 500 000 individuals have or have had cancer [1]. Cancer survivors can experience a wide range of disease and treatment related symptoms, that profoundly affect their health related quality of life. For example, women treated for breast cancer have on average 25 percent lower physical fitness compared to women without a cancer diagnosis. Recent evidence suggests that exercise has a positive effect on physical fitness, muscle strength, cancer related fatigue and quality of life among cancer survivors. An effective exercise prescription for health related outcomes in adult cancer survivors includes aerobic training at a moderate intensity for a total of 150 minutes per week. Adding resistance training two times per week has additional effects on muscle strength and physical functioning. Supervised exercise programs seem to be more effective than unsupervised or home based programs.
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Neoplasias da Mama , Sobreviventes de Câncer , Adulto , Neoplasias da Mama/terapia , Exercício Físico/fisiologia , Feminino , Humanos , Força Muscular , Qualidade de VidaRESUMO
INTRODUCTION: In early breast cancer, neoadjuvant chemotherapy (NACT) is increasingly used. The proof of efficacy is pathologically complete response (pCR), i.e. the absence of invasive tumour in breast and lymph nodes at surgery. Today, pCR is a common endpoint in pharmaceutical trials since it is significantly associated with survival especially in triple-negative and HER2-positive subtypes. Apart from the mitigation of treatment-related toxicity and symptoms, physical exercise mediates anti-tumoral systemic effects associated with tumour regression in preclinical and clinical models. The aim of Neo-ACT is to test the hypothesis that physical exercise can improve pCR rates in breast cancer patients receiving NACT. METHOD: The Neo-ACT trial is a prospective clinical trial, randomising T1-3N0-2 breast cancer patients planned for NACT to either a home-based physical exercise intervention supported by a mobile application or routine care. The primary endpoint is pCR; secondary endpoints are patient-reported quality of life, toxicity-related outcomes, and oncological outcomes such as Residual Cancer Burden, objective radiological tumour response, as well as overall, breast cancer-specific and disease-free survival at 2, 5 and 10 years. The intervention consists of a combination of high-intensity interval and resistance training of progressing intensity, and includes at least 150 min of moderate to vigorous physical activity per week, inclusive of two weekly 60-min exercise sessions. In order to show an improvement in pCR of 10%, a total of 712 participants need to be included in the analysis. The Neo-ACT has been registered at clinicaltrials.gov on January 11, 2022 (NCT05184582). EXPECTED RESULTS: If Neo-ACT can prove the oncological efficacy of physical exercise, implementation of training programmes into NACT schedules will be pursued. The use of a digitally led exercise intervention aims to test the potential of such a strategy for use in rural areas and areas of limited resources.
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Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Exercício Físico , Feminino , Humanos , Preparações Farmacêuticas , Estudos Prospectivos , Qualidade de VidaRESUMO
Breast cancer is the most common form of cancer among women in Sweden. Several decades ago it was recognized that the Human epidermal growth factor receptor 2 (HER2) is involved in a critical growth system for breast cancer cells. Overexpression of HER2 (immunohistochemistry [IHC] 2+/3+, in situ hybridization [ISH] positive) is present in 15 percent of all breast cancers. HER2-low breast cancer has been discovered as a separate entity; the most commonly used definition so far is IHC 1+/2+ and ISH negative, but general consensus is still lacking. Clinical studies with the HER2 antibody drug conjugate trastuzumab deruxtecan (Enhertu) have shown impressive antitumor activity among women with advanced HER2-low breast cancer and this is expected to become part of routine treatment in the near future. Research is needed to establish refined ways to define HER2-low breast cancer, and a possible role lies in new imaging methods such as HER2 positron emission tomography (PET) with a [68Ga]Ga-ABY-025 tracer.
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Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Imuno-Histoquímica , Tomografia por Emissão de Pósitrons/métodos , Suécia/epidemiologiaRESUMO
BACKGROUND: Cancer treatment-related morbidity relevantly compromises health status in cancer survivors, and efforts to optimise health-related outcomes in this population are vital to maximising healthy survivorship. A pre-treatment assessment - and possibly preventive management strategies - of cancer patients at increased risk for cardiovascular disease (CVD) seems a rational approach in this regard. Definitive evidence for such strategies is largely lacking, thereby impeding the formulation of firm recommendations. RESULTS: The current scoping review aims to summarise and grade the evidence regarding strategies for prediction and prevention of CVD in adults in relation to oncological treatments. We conducted a scoping literature search for different strategies for primary prevention, such as medical and lifestyle interventions, as well as the use of predictive risk scores. We identified studies with moderate to good strength and up to now limited evidence to recommend primary preventive strategies in unselected patients treated with potentially cardiotoxic oncologic therapies. CONCLUSION: Efforts to minimize the CVD burden in cancer survivors are needed to accomplish healthy survivorship. This can be done by means of robust models predictive for CVD events or application of interventions during or after oncological treatments. Up to now there is insufficient evidence to implement preventive strategies in an unselected group of patients treated with potential cardiotoxic oncological treatments. We conclude that randomised controlled trials are needed that evaluate medical and lifestyle interventions in groups at increased risk for complications, in order to be able to influence chronic illness risks, such as cardiovascular complications, for cancer survivors.
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BACKGROUND: Adjuvant systemic breast cancer treatment improves disease specific outcomes, but also presents with cardiac toxicity. In this post-hoc exploratory analysis of the OptiTrain trial, the effects of exercise on cardiotoxicity were monitored by assessing fitness and biomarkers over the intervention and into survivorship. Methods; Women starting chemotherapy were randomized to 16-weeks of resistance and high-intensity interval training (RT-HIIT), moderate-intensity aerobic and high-intensity interval training (AT-HIIT), or usual care (UC). Outcome measures included plasma troponin-T (cTnT), Nt-pro-BNP and peak oxygen uptake (VO2peak), assessed at baseline, post-intervention, and at 1- and 2-years. RESULTS: For this per-protocol analysis, 88 women met criteria for inclusion. Plasma cTnT increased in all groups post-intervention. At the 1-year follow-up, Nt-pro-BNP was lower in the exercise groups compared to UC. At 2-years there was a drop in VO2peak for patients with high cTnT and Nt-pro-BNP. Fewer patients in the RT-HIIT group fulfilled biomarker risk criteria compared to UC (OR 0.200; 95% CI = 0.055-0.734). CONCLUSIONS: In this cohort, high-intensity exercise was associated with lower levels of NT-proBNP 1-year post-baseline, but not with cTnT directly after treatment completion. This may, together with the preserved VO2peak in patients with low levels of biomarkers, indicate a long-term cardioprotective effect of exercise. TRIAL REGISTRATION: Clinicaltrials. govNCT02522260 , Registered 13th of august 2015 - Retrospectively Registered.
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Cardiovascular toxicity is one of the most devastating complications of cancer treatment and can arise during or shortly after treatment, or even several years later. Identification of the left ventricular ejection fraction (LVEF) is the most common method to screen for toxic effects on the heart; however, this approach underestimates cardiac damage and additional strategies for the monitoring of treatment-induced cardiotoxicity are being explored. Guidelines for monitoring have been formulated for several cancer treatments; however, appropriate underlying evidence is still largely absent. In this Review, we summarise conventional and contemporary methods for early detection of cardiotoxicity and designate a level of evidence for the basis of each method.
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Antineoplásicos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/diagnóstico , Coração/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Diagnóstico Precoce , HumanosRESUMO
Purpose: We evaluate longitudinal changes in symptom clusters and core burdensome symptoms in breast cancer patients who participated in the OptiTrain trial. Methods: 240 women were randomized to 16 weeks of supervised exercise (RT-HIIT or AT-HIIT) or usual care (UC) during adjuvant chemotherapy. Symptom clusters were composed using the Memorial Symptom Assessment Scale (MSAS), assessed at baseline, 16 weeks and 12 months later. Three symptom clusters were formed. Results: Three symptom clusters were identified: "emotional," "treatment-related toxicity," and "physical," with core burdensome symptoms present over time. At 16 weeks, the reported burdens of "feeling sad" (RT-HIIT vs UC: effect size [ES] = -0.69; AT-HIIT vs UC: ES = -0.56) and "feeling irritable" (ES = -0.41 RT-HIIT; ES = -0.31 AT-HIIT) were significantly lower in both intervention groups compared with UC. At 12 months, the AT-HIIT group continued to have significantly lower scores for the core burdensome symptoms "feeling sad" (ES = -0.44), "feeling irritable" (ES = -0.44), and "changes in the way food tastes" (ES = -0.53) compared with UC. No between-group differences were found for physical symptoms. Conclusion: We identified 3 symptom clusters in breast cancer patients during and after adjuvant chemotherapy, composed of "emotional," "treatment-related toxicity," and "physical" symptoms. After treatment completion up to 12 months post-baseline, patients in the physical exercise groups reported lower symptom burden scores for emotional symptoms, compared with UC. Our findings indicate a preserved and long-term beneficial effect of physical exercise on self-reported emotional well-being in chemotherapy-treated breast cancer patients.
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Adaptação Psicológica , Antineoplásicos , Neoplasias da Mama , Quimioterapia Adjuvante/psicologia , Efeitos Psicossociais da Doença , Treinamento Intervalado de Alta Intensidade/métodos , Qualidade de Vida , Treinamento Resistido/métodos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/psicologia , Neoplasias da Mama/reabilitação , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Exercício Físico/fisiologia , Exercício Físico/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Desempenho Físico Funcional , Angústia PsicológicaRESUMO
AIMS: Heart failure (HF) patients diagnosed with breast cancer (BC) may have a higher risk of death, and different HF presentation and treatment than patients without BC. METHODS AND RESULTS: A total of 14 998 women with incident HF (iHF) or prevalent HF (pHF) enrolled in the Swedish HF Registry within and after 1 month since HF diagnosis, respectively, between 2008 and 2013. Patients were linked with the National Patient-, Cancer-, and Cause-of-Death Registry. Two hundred and ninety-four iHF and 338 pHF patients with BC were age-matched to 1470 iHF and 1690 pHF patients without BC. Comorbidity and treatment characteristics were compared using the χ2 tests for categories. Cox proportional hazard models assessed the hazard ratio (HR) and 95% confidence intervals (95% CIs) of all-cause and cardiovascular mortality among HF patients with and without BC. In the pHF group, BC patients had less often myocardial infarction (21.6% vs. 28.6%, P < 0.01) and received less often aspirin (47.6% vs. 55.1%, P = 0.01), coronary revascularization (11.8% vs. 16.2%, P < 0.01), or device therapy (0.9% vs. 3.0%, P = 0.03). After median follow-up of 2 years, risk of all-cause mortality (iHF: HR = 1.04, 95% CI = 0.83-1.29 and pHF: HR = 0.94, 95% CI = 0.79-1.12), cardiovascular mortality (iHF: HR = 0.94, 95% CI = 0.71-1.24 and pHF: HR = 0.89, 95% CI = 0.71-1.10), and HF mortality (iHF: HR = 0.80, 95% CI = 0.34-1.90 and pHF: HR = 0.75, 95% CI = 0.43-1.29) were similar for patients with and without BC in the iHF and pHF groups. CONCLUSION: Risk of all-cause and cardiovascular mortality in HF patients did not differ by BC status. Differences in pre-existing myocardial infarction and HF treatment among pHF patients with and without BC may suggest differences in pathogenesis of HF.
Assuntos
Neoplasias da Mama/complicações , Insuficiência Cardíaca/epidemiologia , Vigilância da População , Sistema de Registros , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Causas de Morte/tendências , Feminino , Seguimentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Humanos , Prevalência , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Suécia/epidemiologiaRESUMO
Anaplastic thyroid carcinoma (ATC) exhibits an exceedingly poor prognosis, and the current treatment options are, for most cases, palliative by nature. Few reports of long-time survivors exist, although in these patients, tumors often were limited to the thyroid and/or regional lymph nodes. We describe a 64-year-old male who developed a rapidly growing mass in the left thyroid lobe. A fine-needle aspiration biopsy (FNAB) was consistent with ATC, and the patient underwent preoperative combined chemo- and radiotherapy followed by a hemithyroidectomy. The ensuing histopathological investigation was consistent with ATC adjoined by an oxyphilic well-differentiated lesion, likely a Hürthle cell carcinoma. Tumor margins were negative, and no extrathyroidal extension was noted. Focused next-generation sequencing analysis of the primary tumor tissue identified a TP53 gene mutation but could not identify any potential druggable targets. Additional Sanger sequencing detected a C228T TERT promoter mutation. The tumor was found to be microsatellite stable and displayed PDL1 expression in 80% of tumor cells. Following a CT scan 1 month postoperatively, metastatic deposits were suspected in the lung as well as in the left adrenal gland, of which FNAB verified the latter. Remarkably, upon radiological follow-up, the disease had gone into apparent complete remission. The patient is alive and well with no signs of residual disease after 12 months of follow-up. We here summarize the clinical, histological, and molecular data of this highly interesting patient case and review the literature for possible common denominators with other patients with disseminated ATC.