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1.
Anticancer Res ; 41(10): 5045-5052, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593453

RESUMO

BACKGROUND/AIM: To examine the association between sense of coherence (SOC) and health-related quality of life (HRQoL) in early breast cancer patients. PATIENTS AND METHODS: The study population included 406 disease-free breast cancer survivors who participated in 3-year and 5-year follow-ups of a randomized exercise intervention. SOC was assessed using the short version of the Orientation to life questionnaire (SOC-13) in the 3-year follow-up. HRQoL was self-reported using the EORTC QLQC30 questionnaire in both 3-year and 5-year follow-ups. The association between SOC and HRQoL was analyzed using the Spearman's rank correlation coefficient. RESULTS: SOC had a strong positive correlation with global HRQoL in both 3-year (rs=0.57, p<0.01) and 5-year (rs=0.51, p<0.01) follow-ups. CONCLUSION: This study provides evidence of SOC's predictive value for HRQoL in early breast cancer patients. SOC might be used for identifying patients who will profit most from psychosocial support and intervention during the rehabilitation period.


Assuntos
Adaptação Psicológica , Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Qualidade de Vida , Senso de Coerência/fisiologia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Inquéritos e Questionários , Taxa de Sobrevida
2.
Clin Breast Cancer ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34657816

RESUMO

BACKGROUND: The growing number of new breast cancer (BC) patients has indicated an urgent need for better tools to monitor patients. Due to the increasing number of unscheduled patient calls, two digital applications were implemented: a callback application (CA) and a digital cancer follow-up application (CFUA). The aim of this study was to evaluate the implementation and added value of digital applications for healthcare professionals in monitoring BC patients from 2012 to 2020. MATERIALS AND METHODS: As of the end of 2020, 1420 follow-up BC patients were enrolled in the CFUA, which covered 70% of the BC patients in the follow-up phase in the clinic. All unscheduled telephone calls and digital contacts were recorded from January 2015 to December 2020. RESULTS: The implementation of the CA revealed low telephone accessibility (56%), which was improved by 55% by the end of 2020 due to the implementation of the CFUA. In 2019, 59% of all phone service contacts were digitally prepared, and contact reasons were classified by the patients. One of the most important findings was that BC patient contacts more than tripled during the nine-year study period, and these patients could be treated by the same number of nurses due to the implementation of the CA and CFUA. Feedback from two nurses' surveys favored the use of the CFUA. CONCLUSION: Our study clearly demonstrates that new digital tools are useful in the challenge of a growing number of BC patients in surveillance who should be handled with limited health care resources.

3.
Eur Urol Open Sci ; 30: 47-62, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34337548

RESUMO

Background: Systematic identification of data essential for outcome prediction in metastatic prostate cancer (mPC) would accelerate development of precision oncology. Objective: To identify novel phenotypes and features associated with mPC outcome, and to identify biomarker and data requirements to be tested in future precision oncology trials. Design setting and participants: We analyzed deep longitudinal clinical, neuroendocrine expression, and autopsy data of 33 men who died from mPC between 1995 and 2004 (PELICAN33), and related findings to mPC biomarkers reported in the literature. Intervention: Thirty-three men prospectively consented to participate in an integrated clinical-molecular rapid autopsy study of mPC. Outcome measurements and statistical analysis: Data exploration with correction for multiple testing and survival analysis from the time of diagnosis to time to death and time to first occurrence of severe pain as outcomes were carried out. The effect of seven complications on the modeled probability of dying within 2 yr after presenting with the complication was evaluated using logistic regression. Results and limitations: Feature exploration revealed novel phenotypes related to mPC outcome. Four complications (pleural effusion, severe anemia, severe or controlled pain, and bone fracture) predict the likelihood of death within 2 yr. Men with Gleason grade group 5 cancers developed severe pain sooner than those with lower-grade tumors. Surprisingly, neuroendocrine (NE) differentiation was frequently observed in the setting of high serum prostate-specific antigen (PSA) levels (≥30 ng/ml). In 4/33 patients, no controlled (requiring analgesics) or severe pain was detected, and strikingly, 14/15 metastatic sites studied in these men did not express NE markers, suggesting an inverse relationship between NE differentiation and pain in mPC. Intracranial subdural metastasis is common (36%) and is usually clinically undetected. Categorization of "skeletal-related events" complications used in recent studies likely obscures the understanding of spinal cord compression and fracture. Early death from prostate cancer was identified in a subgroup of men with a low longitudinal PSA bandwidth. Cachexia is common (body mass index <0.89 in 24/31 patients) but limited to the last year of life. Biomarker review identified 30 categories of mPC biomarkers in need of winnowing in future trials. All findings require validation in larger cohorts, preferably alongside data from this study. Conclusions: The study identified novel outcome subgroups for future validation and provides "vision for mPC precision oncology 2020-2050" draft recommendations for future data collection and biomarker studies. Patient summary: To better understand variation in metastatic prostate cancer behavior, we assembled and analyzed longitudinal clinical and autopsy records in 33 men. We identified novel outcomes, phenotypes, and aspects of disease burden to be tested and refined in future trials.

4.
Cancers (Basel) ; 13(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34359796

RESUMO

In colorectal cancer (CRC), 20-50% of patients relapse after curative-intent surgery with or without adjuvant therapy. We investigated the lead times and prognostic value of post-adjuvant (8 months from randomisation to adjuvant treatment) serum CEA, CA19-9, IL-6, CRP, and YKL-40. We included 147 radically resected stage II-IV CRC treated with 24 weeks of adjuvant 5-fluorouracil-based chemotherapy in the phase III LIPSYT-study (ISRCTN98405441). All 147 were included in lead time analysis, but 12 relapsing during adjuvant therapy were excluded from post-adjuvant analysis. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired disease-free survival (DFS) with hazard ratio (HR) 5.21 (95% confidence interval 2.32-11.69); 3.72 (1.99-6.95); 2.58 (1.18-5.61), respectively, and elevated IL-6 and CRP with impaired overall survival (OS) HR 3.06 (1.64-5.73); 3.41 (1.55-7.49), respectively. Elevated post-adjuvant IL-6 in CEA-normal patients identified a subgroup with impaired DFS. HR 3.12 (1.38-7.04) and OS, HR 3.20 (1.39-7.37). The lead times between the elevated biomarker and radiological relapse were 7.8 months for CEA and 10.0-53.1 months for CA19-9, IL-6, CRP, and YKL-40, and the lead time for the five combined was 27.3 months. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired DFS. The lead time was shortest for CEA.

5.
JACC CardioOncol ; 3(2): 277-289, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34396335

RESUMO

Background: Radiation therapy (RT) results in myocardial changes consisting of diffuse fibrosis, which may result in changes in diastolic function. Objectives: The aim of this study was to explore RT-associated changes in left ventricular (LV) diastolic function. Methods: Sixty chemotherapy-naive patients with left-sided, early-stage breast cancer were studied with speckle tracking echocardiography at 3 time points: prior to, immediately after, and 3 years after RT. Global and regional early diastolic strain rate (SRe) were quantified, as were parameters of systolic function. Results: Regional changes in SRe, particularly the apical and anteroseptal segments, were observed over time and were more evident than global changes. The apical SRe declined from a median of 1.24 (interquartile range: 1.01 to 1.39) s-1 at baseline to 1.02 (interquartile range: 0.79 to 1.15) s-1 at 3 years of follow-up (p < 0.001). This decline was associated with the left ventricular maximal radiation dose (ß = 0.36, p = 0.007). The global SRe was <1.00 s-1 (SRedep) in 11 (18.3%) patients at baseline, 21 (35%) patients (p = 0.013) post-RT, and 17 (28.3%) patients (p = 0.051) at 3 years. SRedep post-RT was independently associated with baseline cardiac abnormalities (odds ratio: 0.26; 95% confidence interval: 0.08 to 0.84; p = 0.025); SRedep at 3 years of follow-up was associated with the baseline Charlson comorbidity index (odds ratio: 2.36; 95% confidence interval: 1.17 to 4.77; p = 0.017). Diastolic function abnormalities were evident even in patients with preserved global longitudinal strain at 3 years. Conclusions: RT resulted in changes in the SRe in the apical and anteroseptal segments over 3 years of follow-up. Changes in SRe apical segments were present even in patients with preserved systolic function and were independently associated with RT dose and cardiovascular comorbidities.

6.
Cancers (Basel) ; 13(14)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34298839

RESUMO

We studied the prognostic impact of tumor immunoglobulin kappa C (IGKC) mRNA expression as a marker of the humoral immune system in the FinHer trial patient population, where 1010 patients with early breast cancer were randomly allocated to either docetaxel-containing or vinorelbine-containing adjuvant chemotherapy. HER2-positive patients were additionally allocated to either trastuzumab or no trastuzumab. Hormone receptor-positive patients received tamoxifen. IGKC was evaluated in 909 tumors using quantitative real-time polymerase chain reaction, and the influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates. Interactions were analyzed using Cox regression. IGKC expression, included as continuous variable, was independently associated with DDFS in a multivariable analysis also including age, molecular subtype, grade, and pT and pN stage (HR 0.930, 95% CI 0.870-0.995, p = 0.034). An independent association with DDFS was also found in a subset analysis of triple-negative breast cancers (TNBC) (HR 0.843, 95% CI 0.724-0.983, p = 0.029), but not in luminal (HR 0.957, 95% CI 0.867-1.056, p = 0.383) or HER2-positive (HR 0.933, 95% CI 0.826-1.055, p = 0.271) cancers. No significant interaction between IGKC and chemotherapy or trastuzumab administration was detected (Pinteraction = 0.855 and 0.684, respectively). These results show that humoral immunity beneficially influences the DDFS of patients with early TNBC.

7.
BMC Palliat Care ; 20(1): 119, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34311739

RESUMO

BACKGROUND: Physicians' decision-making for seriously ill patients with advanced dementia is of high importance, especially as the prevalence of dementia is rising rapidly, and includes many challenging ethical, medical and juridical aspects. We assessed the change in this decision-making over 16 years (from 1999 to 2015) and several background factors influencing physicians' decision. METHODS: A postal survey including a hypothetical patient-scenario representing a patient with an advanced dementia and a life-threatening gastrointestinal bleeding was sent to 1182 and 1258 Finnish physicians in 1999 and 2015, respectively. The target groups were general practitioners (GPs), surgeons, internists and oncologists. The respondents were asked to choose between several life-prolonging and palliative care approaches. The influence of physicians' background factors and attitudes on their decision were assessed. RESULTS: The response rate was 56%. A palliative care approach was chosen by 57 and 50% of the physicians in 1999 and 2015, respectively (p = 0.01). This change was statistically significant among GPs (50 vs 40%, p = 0.018) and oncologists (77 vs 56%, p = 0.011). GPs chose a palliative care approach less often than other responders in both years (50 vs. 63% in 1999 and 40 vs. 56% in 2015, p < 0.001). In logistic regression analysis, responding in 2015 and being a GP remained explanatory factors for a lower tendency to choose palliative care. The impact of family's benefit on the decision-making decreased, whereas the influence of the patient's benefit and ethical values as well as the patient's or physician's legal protection increased from 1999 to 2015. CONCLUSIONS: Physicians chose a palliative care approach for a patient with advanced dementia and life-threatening bleeding less often in 2015 than in 1999. Specialty, attitudes and other background factors influenced significantly physician decision-making. Education on the identification and palliative care of the patients with late-stage dementia are needed to make these decisions more consistent.


Assuntos
Tomada de Decisões , Demência , Clínicos Gerais , Cuidados Paliativos , Assistência Terminal , Atitude do Pessoal de Saúde , Demência/terapia , Humanos , Padrões de Prática Médica , Inquéritos e Questionários
8.
Breast ; 59: 110-116, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34225091

RESUMO

OBJECTIVE: To investigate long-term health-related quality of life (HRQoL) changes over time in younger compared to older disease-free breast cancer survivors who participated in a prospective randomized exercise trial. METHODS: Survivors (aged 35-68 years) were randomized to a 12-month exercise trial after adjuvant treatment and followed up for ten years. HRQoL was assessed with the generic 15D instrument during follow-up and the younger (baseline age ≤ 50) and older (age >50) survivors' HRQoL was compared to that of the age-matched general female population (n = 892). The analysis included 342 survivors. RESULTS: The decline of HRQoL compared to the population was steeper and recovery slower in the younger survivors (p for interaction < 0.001). The impairment was also larger among the younger survivors (p = 0.027) whose mean HRQoL deteriorated for three years after treatment and started to slowly improve thereafter but still remained below the population level after ten years (difference -0.017, 95% CI: -0.031 to -0.004). The older survivors' mean HRQoL gradually approached the population level during the first five years but also remained below it at ten years (difference -0.019, 95% CI: -0.031 to -0.007). The largest differences were on the dimensions of sleeping and sexual activity, on which both age groups remained below the population level throughout the follow-up. CONCLUSIONS: HRQoL developed differently in younger and older survivors both regarding the most affected dimensions of HRQoL and the timing of the changes during follow-up. HRQoL of both age groups remained below the population level even ten years after treatment.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Neoplasias da Mama/terapia , Feminino , Humanos , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Sobreviventes
9.
BMC Public Health ; 21(1): 629, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789632

RESUMO

BACKGROUND: Physical activity (PA) is known to be associated with lipid profiles and the risk of both cardiovascular diseases and cancer. The aim of this study was to evaluate the association of objectively measured PA, sedentary behaviour (SB), amount of breaks during SB and number of daily steps with serum lipids in a healthy, Finnish, middle-aged, female population. METHODS: The participants (571) were recruited at mammography screening, target group was women aged 50-60 years. A measurement of PA was done with accelerometer, blood lipid profile was assessed, and questionnaires of participants characteristics were sent to participants. RESULTS: The participants with the highest number of daily breaks during SB (≥ 41) had the highest mean concentration of HDL-cholesterol (high density lipoprotein cholesterol, HDL-c) (1.9 mmol/l, standard deviation (SD) 0.4) and the lowest mean concentration of triglycerides (1.0 mmol/l, SD 0.5). HDL-c level was 0.16 mmol/l higher (p < 0.001) in the group with 28-40.9 breaks/day and 0.25 mmol/l higher (p < 0.001) among participants with ≥41 breaks/day than in the group with the fewest breaks during SB (< 28). Those with the most daily steps (≥ 9100) had the highest mean HDL-c level (1.9 mmol/l). HDL-c level was 0.16 mmol/l higher (p < 0.001) among the participants with 5600-9099 steps/day and 0.26 mmol/l higher (p < 0.001) among participants with ≥9100 steps/day than those with the fewest steps (< 5600). The number of daily steps was inversely associated with the triglyceride concentration. From wake-time, participants spent 60% in SB, 18% standing, 14% in light PA, and 9% in moderate-to-vigorous PA (MVPA). PA was associated with serum total cholesterol (TC), HDL-c and triglyceride levels. The mean HDL-c level was the highest in the lowest quartile of SB and in the highest quartile of MVPA. CONCLUSIONS: To our knowledge, this is the first study showing a high number of objectively measured breaks during SB is associated with a favourable effect on the level of serum lipids, which may later translate into cardiovascular health among middle-aged women. TRIAL REGISTRATION: This study was registered and approved by the Regional Ethics Committee of Tampere University Hospital in Finland (approval code R15137 ).


Assuntos
Exercício Físico , Comportamento Sedentário , HDL-Colesterol , Feminino , Finlândia , Humanos , Lipídeos , Pessoa de Meia-Idade
10.
Sci Rep ; 11(1): 4037, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597560

RESUMO

The treatment of patients with ERBB2 (HER2)-positive breast cancer with anti-ERBB2 therapy is based on the detection of ERBB2 gene amplification or protein overexpression. Machine learning (ML) algorithms can predict the amplification of ERBB2 based on tumor morphological features, but it is not known whether ML-derived features can predict survival and efficacy of anti-ERBB2 treatment. In this study, we trained a deep learning model with digital images of hematoxylin-eosin (H&E)-stained formalin-fixed primary breast tumor tissue sections, weakly supervised by ERBB2 gene amplification status. The gene amplification was determined by chromogenic in situ hybridization (CISH). The training data comprised digitized tissue microarray (TMA) samples from 1,047 patients. The correlation between the deep learning-predicted ERBB2 status, which we call H&E-ERBB2 score, and distant disease-free survival (DDFS) was investigated on a fully independent test set, which included whole-slide tumor images from 712 patients with trastuzumab treatment status available. The area under the receiver operating characteristic curve (AUC) in predicting gene amplification in the test sets was 0.70 (95% CI, 0.63-0.77) on 354 TMA samples and 0.67 (95% CI, 0.62-0.71) on 712 whole-slide images. Among patients with ERBB2-positive cancer treated with trastuzumab, those with a higher than the median morphology-based H&E-ERBB2 score derived from machine learning had more favorable DDFS than those with a lower score (hazard ratio [HR] 0.37; 95% CI, 0.15-0.93; P = 0.034). A high H&E-ERBB2 score was associated with unfavorable survival in patients with ERBB2-negative cancer as determined by CISH. ERBB2-associated morphology correlated with the efficacy of adjuvant anti-ERBB2 treatment and can contribute to treatment-predictive information in breast cancer.

11.
Clin Breast Cancer ; 21(3): e252-e270, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33229222

RESUMO

INTRODUCTION: Patient-reported outcomes (PROs) have become extremely important in following patients' health-related quality of life during cancer treatments. The aim of this study was to assess the usefulness of electronic PROs (ePROs) during adjuvant radiotherapy (RT) in patients with early breast cancer. MATERIALS AND METHODS: A registry trial was conducted with a total of 253 patients with breast cancer receiving RT. Adverse event data were collected from 9 items on the ePRO questionnaires that were administered before RT (N = 253), at the end of RT (± 3 days; N = 234), 1 month after RT (N = 230), and 3 months (N = 225) after RT. The patient characteristics and treatment details were collected from the medical records. RESULTS: The patients have started actively using the ePRO system, and the response rates were high (82.6%). During RT, 39.3% of the ePRO responses were about symptoms, and 60.7% were about treatment-related questions or advice. Patients treated with hypofractionated RT reported fewer local adverse events such as skin symptoms (P = .001) and pain (P = .002) than those who received conventional RT. One of the main findings of this study was that tiredness, fatigue, and anxiety were commonly reported on the patients' ePRO questionnaires, but they were rarely recorded in the medical records. CONCLUSION: Patients were motivated to use the ePRO system, and the response rates were high. Additionally, patients seemed to find that the ePRO system was an easy way to contact their own health care professionals. More attention should be paid to mental well-being during visits to the clinic.

12.
Anticancer Res ; 40(12): 6915-6921, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33288585

RESUMO

BACKGROUND/AIM: Our phase III trial showed that biweekly docetaxel (D) is better tolerated than triweekly D in metastatic castration-resistant prostate cancer (mCRPC). The safety of biweekly cabazitaxel (CBZ) post-docetaxel was studied in mCRPC. PATIENTS AND METHODS: Altogether, 60 patients received CBZ 16 mg/m2 i.v. on day 1 and day 14 of a 4-week cycle. The mean serum PSA levels were 305 ng/ml, and the mean age 67 years. The primary endpoint was safety according to CTCAEv4.0. RESULTS: A total of 255 4-week cycles of CBZ were administered. The most common grade 3/4 adverse events were neutropenia (16.7%), pain (13.3%), fatigue (10.0%), anemia (5.0%) and non-neutropenic infection (10.0%). PSA responses occurred in 10 patients (16.7%). Clinical benefit rate was 38.3% and median survival 10 months. CONCLUSION: Biweekly CBZ is a well-tolerated treatment resulting in meaningful benefits for heavily pretreated mCRPC patients.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Biomarcadores , Docetaxel/uso terapêutico , Esquema de Medicação , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Qualidade de Vida , Retratamento , Taxoides/efeitos adversos , Resultado do Tratamento
14.
Eur J Haematol ; 105(6): 712-721, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32632935

RESUMO

OBJECTIVES: Testicular diffuse large B-cell lymphoma (T-DLBCL) is a rare and aggressive extranodal lymphoma. We have previously shown that high content of tumor-infiltrating lymphocytes (TILs) and PD-1 expressing TILs associate with better survival in T-DLBCL. In this study, we have further characterized distinct TIL subtypes and their proportions in association with patient demographics and survival. METHODS: We used multiplex immunohistochemistry to characterize TIL phenotypes, including cytotoxic T-cells (CTLs; CD8+ , OX40+ , Granzyme B+ , Ki-67+ , LAG-3+ , TIM-3+ , PD-1+ ), CD4+ T-cells (CD3+ , CD4+ , TIM-3+ , LAG-3+ ), regulatory T-cells (Tregs; CD3+ , CD4+ , FoxP3+ ), and T helper 1 cells (Th1; CD3+ , CD4+ , T-bet+ ) in 79 T-DLBCLs, and correlated the findings with patient demographics and outcome. RESULTS: We observed a substantial variation in TIL phenotypes between the patients. The most prominent CD8+ TILs were Ki-67+ and TIM-3+ CTLs, whereas the most prominent CD4+ TILs were FoxP3+ Tregs. Despite the overall favorable prognostic impact of high TIL content, we found a subpopulation of T-bet+ FoxP3+ Tregs that had a significant adverse impact on survival. Lower content of CTLs with activated or exhausted phenotypes correlated with aggressive clinical features. CONCLUSIONS: Our results demonstrate significant variation in TIL phenotypes and emphasize the adverse prognostic impact of Tregs in T-DLBCL.


Assuntos
Linfócitos do Interstício Tumoral/patologia , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Linfócitos T Reguladores/patologia , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia , Progressão da Doença , Humanos , Imuno-Histoquímica , Imunofenotipagem , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Prognóstico , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
15.
BMC Cancer ; 20(1): 324, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295542

RESUMO

BACKGROUND: In this retrospective study, we evaluated the biochemical recurrence rate, metastatic disease progression, and prostate cancer-specific and overall survival in patients curatively treated with external beam radiotherapy (EBRT) for early prostate cancer (PC). We also examined the prognostic effect of comorbidity by Charlson Comorbidity Index (CCI) and overall performance status by Eastern Clinical Oncology Group (ECOG) score. METHODS: A total of 665 men treated between 2008 and 2013 were enrolled from Tampere University Hospital, Finland. Prostate-specific antigen (PSA) tests and hospital records were used to determine the 5-year survival for each aforementioned endpoint using a Kaplan-Meyer estimate. To analyze the impact of the selected prognostic factor, we used a Cox regression model to calculate the corresponding hazard ratio (HR) and 95% confidence interval (CI). RESULTS: With a median follow-up-time of 7.12 years, the 5-year overall survival (OS) after EBRT was 88.9% [86.5 -91.3%], prostate cancer-specific survival (PCSS) was 97.9% [96.7 -99.1%], metastasis-free survival (MFS) 94.8% [93.0 -96.6%] and biochemical recurrence-free survival (BRFS) 88.7% [86.2 -91.2%]. Both CCI (HR = 1.38, [1.25-1.51]) and ECOG score (HR = 1.63, [1.29-2.05]) declined OS, as well as Gleason score and T score (P <  0.05). Gleason score and T grade also associated to worse PCSS, MFS and BRFS. CONCLUSIONS: CCI and ECOG score are useful tools in evaluating the overall life expectancy of the patient after EBRT for PC. T-stage and Gleason score remain still the major prognostic factors.


Assuntos
Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Progressão da Doença , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Neoplasias da Próstata/metabolismo , Estudos Retrospectivos , Resultado do Tratamento
16.
In Vivo ; 34(2): 667-674, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32111767

RESUMO

BACKGROUND/AIM: As the number of breast cancer survivors is increasing, their long-term health-related quality of life (HRQoL) has become an important issue. The aim of the study is to follow up the HRQoL of breast cancer survivors (BCS) in a prospective randomized exercise intervention study and to compare HRQoL to that of the age-matched general female population. PATIENTS AND METHODS: Following adjuvant treatment, 537 patients aged 35-68 and capable of exercise training were randomized to a 12-month exercise trial. In 182 of those patients, HRQoL was measured by the generic 15D at baseline and followed up for five years. Furthermore, the HRQoL of all BCS answering the 15D at five-year follow-up (n=390) was compared to that of a representative sample of the general population. RESULTS: After five years, the BCS' mean HRQoL demonstrated a statistically and clinically significant impairment compared to that of the general population (difference -0.023, p<0.001). The mean HRQoL of BCS followed up from baseline until five years did not improve significantly (change=0.007, p=0.27), whereas the dimensions of usual activities (0.043, p=0.004), depression (0.038, p=0.007), distress (0.030, p=0.036), and sexual activity (0.057, p=0.009) did. CONCLUSION: The HRQoL of BCS was still impaired five years following treatment.


Assuntos
Neoplasias da Mama/terapia , Sobreviventes de Câncer/estatística & dados numéricos , Terapia por Exercício/métodos , Qualidade de Vida , Adulto , Idoso , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Estudos Prospectivos , Inquéritos e Questionários , Fatores de Tempo
17.
Int J Cancer ; 147(1): 266-276, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31904863

RESUMO

We investigated the value of reactive stroma as a predictor for trastuzumab resistance in patients with early HER2-positive breast cancer receiving adjuvant therapy. The pathological reactive stroma and the mRNA gene signatures that reflect reactive stroma in 209 HER2-positive breast cancer samples from the FinHer adjuvant trial were evaluated. Levels of stromal gene signatures were determined as a continuous parameter, and pathological reactive stromal findings were defined as stromal predominant breast cancer (SPBC; ≥50% stromal) and correlated with distant disease-free survival. Gene signatures associated with reactive stroma in HER2-positive early breast cancer (N = 209) were significantly associated with trastuzumab resistance in estrogen receptor (ER)-negative tumors (hazard ratio [HR] = 1.27 p interaction = 0.014 [DCN], HR = 1.58, p interaction = 0.027 [PLAU], HR = 1.71, p interaction = 0.019 [HER2STROMA, novel HER2 stromal signature]), but not in ER-positive tumors (HR = 0.73 p interaction = 0.47 [DCN], HR = 0.71, p interaction = 0.73 [PLAU], HR = 0.84; p interaction = 0.36 [HER2STROMA]). Pathological evaluation of HER2-positive/ER-negative tumors suggested an association between SPBC and trastuzumab resistance. Reactive stroma did not correlate with tumor-infiltrating lymphocytes (TILs), and the expected benefit from trastuzumab in patients with high levels of TILs was pronounced only in tumors with low stromal reactivity (SPBC <50%). In conclusion, reactive stroma in HER2-positive/ER-negative early breast cancer tumors may predict resistance to adjuvant trastuzumab therapy.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Trastuzumab/farmacologia , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Ensaios Clínicos Fase III como Assunto , Resistencia a Medicamentos Antineoplásicos , Feminino , Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ensaios Clínicos Controlados Aleatórios como Assunto , Células Estromais/enzimologia , Células Estromais/patologia , Transcriptoma , Fator de Crescimento Transformador beta1/metabolismo , Trastuzumab/uso terapêutico
18.
Breast ; 49: 183-186, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31862685

RESUMO

OBJECTIVES: To search for biomarkers of RT-induced cardiotoxicity, we studied the behavior of ST2 during RT and three years after RT, and the associations with echocardiographic changes. MATERIALS AND METHODS: We measured soluble ST2 (ng/ml) in serum samples from 63 patients receiving RT for early breast cancer. Sampling and echocardiography were performed at baseline, after RT and at the three-year follow-up. Patients were grouped by >15% (group 1) and ≤15% (group 2) relative worsening in global longitudinal strain (GLS). RESULTS: ST2 levels tended to increase during RT, from a median (interquartile range; IQR) of 17.9 (12.4-22.4) at baseline to 18.2 (14.1-23.5) after RT (p = 0.075). By the three-year follow up, ST2 levels increased to 18.7 (15.8-24.2), p = 0.018. The increase in ST2 level was associated with worsening cardiac systolic function at three-year follow-up, GLS (rho = 0.272, p = 0.034) and left ventricular ejection fraction (LVEF) (rho = â”€0.343, p = 0.006). Group 1 (n = 14) had a significant increase in ST2 levels from 17.8 (12.3-22.5) at baseline to 18.4 (15.6-22.6) after RT, p = 0.035 and to 19.9 (16.0-25.1) three years after RT, p = 0.005. ST2 levels were stable in group 2 (n = 47): 17.8 (12.3-22.0) at baseline, 17.7 (12.6-23.5) after RT and 18.0 (15.5-22.4) at three years. CONCLUSION: ST2 may be useful for determining which patients are at risk for long-term cardiovascular toxicity following adjuvant breast cancer RT, but prospective clinical studies are needed to confirm this hypothesis.


Assuntos
Neoplasias da Mama/radioterapia , Cardiotoxicidade/fisiopatologia , Ecocardiografia , Radioterapia Adjuvante/efeitos adversos , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/etiologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Volume Sistólico/efeitos da radiação , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda/efeitos da radiação
19.
Anticancer Res ; 39(11): 5867-5877, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704811

RESUMO

BACKGROUND/AIM: The aim of this study was to examine clonal heterogeneity, to test the utility of liquid biopsy in monitoring disease progression and to evaluate the usefulness of ex vivo drug screening in a BRAF L597Q-mutated colorectal cancer (CRC) patient developing metastases during adjuvant therapy. MATERIALS AND METHODS: Next generation sequencing (NGS) and droplet digital PCR (ddPCR) were performed in samples from tumor tissues and liquid biopsies. Live cancer cells from a metastatic lesion were used in ex vivo drug sensitivity assays. RESULTS: We found evidence of continued dependence of MEK/MAPK pathway activation, but different activating mutations in primary tumor and metastases. Liquid biopsy based BRAF L597Q ddPCR testing was a sensitive personalized biomarker predicting the rise of clinically aggressive metastatic disease. Ex vivo drug sensitivity assays with BRAF L597Q mutated cells showed response to MEK/MAPK targeted therapies. CONCLUSION: The rare BRAF L597Q mutation may be associated with aggressive tumor behavior in CRC. Liquid biopsy can be used to capture clinically relevant tumor features.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/secundário , MAP Quinase Quinase 1/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Mutação , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Capecitabina/administração & dosagem , Evolução Clonal , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , MAP Quinase Quinase 1/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Oxaliplatina/administração & dosagem , Prognóstico
20.
Anticancer Res ; 39(10): 5353-5359, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570429

RESUMO

BACKGROUND: Identification of genetic prognostic biomarkers, such as germline variants, are urgently needed to choose optimal treatment for metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: The prognostic value of anoctamin 7 (ANO7) rs77559646 on docetaxel response was tested in a prospective PROSTY randomized trial and a retrospective Auria Biobank set. The variant rs77559646 was genotyped and its association with progression-free survival (PFS) and overall survival (OS) was tested. RESULTS: In comparison with the non-carriers, the variant carriers had longer PFS (p=0.005) and OS (p=0.003) in the PROSTY cohort. In the retrospective cohort, there was a borderline association with PFS (p=0.09), but not in OS (p=0.9). In both cohorts, Cox regression multivariate models revealed that rs77559646 was an independent prognostic factor for favourable PFS. CONCLUSION: The rs77559646 was shown to be a prognostic germline biomarker for better response to docetaxel treatments. To our knowledge, this is the first time that a non-coding germline variant has been associated with chemotherapy of mCRPC.


Assuntos
Anoctaminas/genética , Antineoplásicos/uso terapêutico , Docetaxel/uso terapêutico , Variação Genética/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Idoso , Biomarcadores Tumorais/genética , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos
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