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OBJECTIVE: To assess the degree of openness of communication about illness and death between patients with advanced cancer and their relatives during the last three months of the patient's life, and its association with relatives' characteristics and bereavement distress. METHODS: We used data from bereaved relatives of patients with advanced cancer from the prospective, longitudinal, multicenter, observational eQuipe study. Univariate and multivariable linear regression analyses were used to assess the association between the degree of openness of communication (measured using the validated Caregivers' Communication with patients about Illness and Death scale), the a priori defined characteristics of the relatives, and the degree of bereavement distress (measured using the Impact of Event Scale). RESULTS: A total of 160 bereaved relatives were included in the analysis. The average degree of open communication about illness and death between patients with advanced cancer and their relatives was 3.86 on a scale of 1 to 5 (SE=0.08). A higher degree of open communication was associated with a lower degree of bereavement distress (p=0.003). No associations were found between the degree of open communication and the relatives' age (p=0.745), gender (p=0.196), level of education (p>0.773), (religious) worldview (p=0.435), type of relationship with the patient (p>0.548), or level of emotional functioning before the patient's death (p=0.075). CONCLUSIONS: Open communication about illness and death between patients and relatives seems to be important, as it is associated with a lower degree of bereavement distress. Healthcare professionals can play an important role in encouraging the dialogue. However, it is important to keep in mind that some people not feel comfortable talking about illness and death.
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Aflicción , Neoplasias , Humanos , Estudios Prospectivos , Pesar , ComunicaciónRESUMEN
BACKGROUND: Immune checkpoint inhibitors (ICIs) can induce durable disease control in metastatic urothelial cancer (mUC), but only 20-25% of patients respond. Early identification of a nondurable response will improve management strategies. OBJECTIVE: To investigate whether on-treatment circulating tumor DNA (ctDNA) measurements can predict ICI responsiveness in mUC patients. DESIGN, SETTING, AND PARTICIPANTS: This study consists of a discovery cohort of 40 mUC patients and a prospective multicenter validation cohort of 16 mUC patients. Plasma cell-free DNA was collected at baseline and after 3 and 6 wk on ICIs. The ctDNA levels were calculated from targeted sequencing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcome measurements were progression-free survival (PFS), overall survival (OS), and nondurable response (PFS ≤6 mo). Relationships with ctDNA were assessed using Cox regression. Changes in ctDNA level at 3 and 6 wk were categorized by an increase or decrease relative to baseline. RESULTS AND LIMITATIONS: In the discovery cohort, ctDNA was detected in 37/40 (93%) of patients at baseline. A ctDNA increase was observed in 12/15 (80%) and ten of 12 (83%) patients with a nondurable response at 3 and 6 wk, respectively. Of patients with a durable response (PFS >6 mo), 94% showed a decrease. A ctDNA increase at 3 wk was associated with shorter PFS (hazard ratio [HR] 7.8, 95% confidence interval [CI] 3.1-19.5) and OS (HR 8.0, 95% CI 3.0-21.0), independent of clinical prognostic variables. Similar results were observed at 6 wk. The 3-wk association with PFS was validated in a prospective cohort (HR 7.5, 95% CI 1.3-42.6). Limitations include the limited number of patients. CONCLUSIONS: Early changes in ctDNA levels are strongly linked to the duration of ICI benefit in mUC and may contribute to timely therapy modifications. PATIENT SUMMARY: Benefit from immunotherapy can be predicted after only 3 wk of treatment by investigating cancer DNA in blood. This could help in timely therapy changes for urothelial cancer patients with limited benefit from immunotherapy.
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ADN Tumoral Circulante , Neoplasias Pulmonares , Humanos , ADN Tumoral Circulante/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estudios Prospectivos , MutaciónRESUMEN
OBJECTIVE: Advanced cancer has a major impact on both patients and their relatives. To allow for personalized support, it is important to recognize which relatives will experience a decline in emotional functioning during the patient's last year of life, when this decline will occur, and what factors are associated with it. This study aimed to examine the trajectory of emotional functioning of relatives during that time and the characteristics associated with changes in this trajectory. METHODS: A prospective, longitudinal, multicenter, observational study in patients with advanced cancer and their relatives was conducted (eQuiPe). We analyzed relatives' changes in emotional functioning in the patient's last year using the EORTC QLQ-C30 and assessed associations with sociodemographic and care characteristics using multivariable mixed-effects analysis. RESULTS: 409 relatives completed ≥1 questionnaires during the patient's last year of life. Mean age was 64 years, 61% were female and 75% were the patient's partner. During this year, mean emotional functioning declined significantly over time from 73.9 to 64.6 (p = 0.023, effect size = 0.43). The type of relationship between relatives and patients (p = 0.002), patient' sleep problems (p = 0.033), and continuity of care (p = 0.002) were significantly associated with changes in emotional functioning. CONCLUSIONS: Relatives' emotional functioning declined during the patient's last year of life. Support for them, especially partners and relatives of patients with sleep problems, is important. Relatives who experienced more continuity of care had a less steep decline in emotional functioning.
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Neoplasias , Trastornos del Sueño-Vigilia , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Prospectivos , Calidad de Vida , Emociones , Neoplasias/terapia , Encuestas y CuestionariosRESUMEN
BACKGROUND: Manual data collection is still the gold standard for disease-specific patient registries. However, CAPRI-3 uses text mining (an artificial intelligence (AI) technology) for patient identification and data collection. The aim of this study is to demonstrate the reliability and efficiency of this AI-driven approach. METHODS: CAPRI-3 is an observational retrospective multicenter cohort registry on metastatic prostate cancer. We tested the patient-identification algorithm and automated data extraction through manual validation of the same patients in two pilots in 2019 and 2022. RESULTS: Pilot one identified 2030 patients and pilot two 9464 patients. The negative predictive value of the algorithm was maximized to prevent false exclusions and reached 94.8%. The completeness and accuracy of the automated data extraction were 92.3% or higher, except for date fields and inaccessible data (images/pdf) (10-88.9%). Additional manual quality control took over 3 h less time per patient than the original fully manual CAPRI registry (105 vs. 300 min). CONCLUSIONS: The CAPRI-3 patient-identification algorithm is a sound replacement for excluding ineligible candidates. The AI-driven data extraction is largely accurate and complete, but manual quality control is needed for less reliable and inaccessible data. Overall, the AI-driven approach of the CAPRI-3 registry is reliable and timesaving.
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INTRODUCTION: Prospective data about quality of life (QoL) in men with breast cancer (BC) are lacking. A prospective registry (EORTC10085) of men with all BC stages, including a QoL correlative study, was performed as part of the International Male Breast Cancer Program. METHODS: Questionnaires at BC diagnosis included the EORTC QLQ-C30 and BR23 (BC specific module), adapted for men. High functioning and global health/QoL scores indicate high functioning levels/high QoL; high symptom-focused measures scores indicate high symptoms/problems levels. EORTC reference data for healthy men and women with BC were used for comparisons. RESULTS: Of 422 men consenting to participate, 363 were evaluable. Median age was 67 years, and median time between diagnosis and survey was 1.1 months. A total of 114 men (45%) had node-positive early disease, and 28 (8%) had advanced disease. Baseline mean global health status score was 73 (SD: 21), better than in female BC reference data (62, SD: 25). Common symptoms in male BC were fatigue (22, SD: 24), insomnia (21, SD: 28), and pain (16, SD: 23), for which women's mean scores indicated more burdensome symptoms at 33 (SD: 26), 30 (SD: 32), and 29 (SD: 29). Men's mean sexual activity score was 31 (SD: 26), with less sexual activity in older patients or advanced disease. CONCLUSIONS: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses on impact of treatment on symptoms and QoL over time, may support tailoring of male BC management.
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Neoplasias de la Mama Masculina , Neoplasias de la Mama , Femenino , Humanos , Masculino , Anciano , Preescolar , Calidad de Vida , Neoplasias de la Mama Masculina/terapia , Estudios Prospectivos , Estado de Salud , Neoplasias de la Mama/terapia , Encuestas y CuestionariosRESUMEN
PURPOSE: To evaluate guideline adherence and variation in the recommended use of neoadjuvant chemotherapy (NAC) and the effects of this variation on survival in patients with non-metastatic muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: In this nationwide, Netherlands Cancer Registry-based study, we identified 1025 patients newly diagnosed with non-metastatic MIBC between November 2017 and November 2019 who underwent radical cystectomy. Patients with ECOG performance status 0-1 and creatinine clearance ≥ 50 mL/min/1.73 m2 were considered NAC-eligible. Interhospital variation was assessed using case-mix adjusted multilevel analysis. A Cox proportional hazards model was used to evaluate the association between hospital specific probability of using NAC and survival. All analyses were stratified by disease stage (cT2 versus cT3-4a). RESULTS: In total, of 809 NAC-eligible patients, only 34% (n = 277) received NAC. Guideline adherence for NAC in cT2 was 26% versus 55% in cT3-4a disease. Interhospital variation was 7-57% and 31-62%, respectively. A higher hospital specific probability of NAC might be associated with a better survival, but results were not statistically significant (HRcT2 = 0.59, 95% CI 0.33-1.05 and HRcT3-4a = 0.71, 95% CI 0.25-2.04). CONCLUSION: Guideline adherence regarding NAC use is low and interhospital variation is large, especially for patients with cT2-disease. Although not significant, our data suggest that survival of patients diagnosed in hospitals more inclined to give NAC might be better. Further research is warranted to elucidate the underlying mechanism. As literature clearly shows the potential survival benefit of NAC in patients with cT3-4a disease, better guideline adherence might be pursued.
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Terapia Neoadyuvante , Neoplasias de la Vejiga Urinaria , Humanos , Terapia Neoadyuvante/métodos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Vejiga Urinaria/patología , Cistectomía/métodos , Músculos , Quimioterapia Adyuvante , Invasividad Neoplásica , Estudios RetrospectivosRESUMEN
Objectives: Studies suggest that advance care planning (ACP) results in improved quality of life and reduced healthcare consumption. We assessed how the use of a structured advance care planning tool (ACPT) in oncology patients relates to their healthcare consumption before death, and to the match between preferred and actual place of death. Methods: We performed a pilot study at a teaching hospital in the Netherlands. Endpoints were 1) healthcare consumption at three and one month(s) before death, and 2) the match between preferred and actual place of death. Results: The study included 75 patients without an ACPT (group 1) and 59 patients with an ACPT (group 2) of whom the preferred place of care or death were documented at least three months before death in 15 patients (subgroup 2b). Compared to group 1, patients in group 2 had significantly more healthcare consumption. However, compared to group 1, patients in subgroup 2b underwent significantly less diagnostic (33.3% (n = 5) versus 69.3% (n = 52), p < 0.05) and laboratory tests (33.3% (n = 5) versus 62.7% (n = 47), p < 0.05) one month before death. Patients in subgroup 2b died at their preferred place more often (76.9%, n = 10) compared to patients in group 1 (58.3%, n = 7) (NS), which meant more deaths at home and less in-hospital-deaths. Conclusions: The results suggest that timely documentation of the preferred place of care or death in a structured ACPT may result in less healthcare consumption and a better match between the preferred and actual place of death.
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Planificación Anticipada de Atención , Neoplasias , Cuidado Terminal , Humanos , Proyectos Piloto , Estudios Retrospectivos , Calidad de Vida , Neoplasias/terapia , Cuidados PaliativosRESUMEN
OBJECTIVE: The death of a loved one is considered to be the most stressful of all life events. However, the impact of bereavement on quality of life varies between individuals. The aim of our study was to assess emotional functioning (EF), which is a domain of quality of life, of bereaved relatives after the death of their loved one and its associated factors. METHOD: A prospective, longitudinal, multicenter, observational study on quality of care and quality of life of patients with advanced cancer and their relatives was conducted (eQuiPe). The association between EF of relatives during bereavement and the following factors was investigated: gender, type of relationship, educational level, pre-bereavement emotional and social functioning and global quality of life, social support pre- and during bereavement, anticipatory complicated grief, support of healthcare professionals during bereavement, age of patient and bereaved relative and duration of survival after primary cancer diagnosis. RESULTS: 150 bereaved relatives completed the bereavement questionnaire. In 41% of the bereaved relatives EF was ≤71, indicating clinically relevant low EF. Multivariable logistic regression showed that females experienced more often emotional problems (OR = 2.82). Emotional functioning pre-bereavement (OR = 0.96) and social support during bereavement (OR = 0.97) were associated with low EF during bereavement. CONCLUSIONS: Almost half of the bereaved relatives of patients with advanced cancer experienced low EF and this was associated with low EF pre-bereavement and low social support during bereavement. Support for relatives should be initiated before the patient's death. Future research is needed to investigate the impact of such support on relatives' wellbeing during bereavement.
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Aflicción , Neoplasias , Familia/psicología , Femenino , Pesar , Humanos , Estudios Prospectivos , Calidad de VidaRESUMEN
OBJECTIVE: How patients and their partners cope with advanced cancer as a couple, may impact their emotional functioning (EF). The aim of this study was to assess dyadic coping (DC) of couples confronted with advanced cancer and its association with EF. METHODS: Actor-partner interdependence models were used to analyze baseline data of 566 couples facing advanced cancer participating in an observational study on quality of care and life. Measures included the DC Inventory and the European Organization for Research and Treatment of Cancer quality of life questionnaire (EOQLQ-C30). RESULTS: Negative DC (mean 86-88) was most often used and common DC (both mean 66) was least often used. We found small to moderate interdependence (r = 0.27-0.56) between patients' and partners' DC perceptions. Compared to partners, patients were more satisfied with their DC (p < 0.001). Partners' satisfaction with DC was positively associated with their own (B = 0.40, p < 0.001) and patients' (B = 0.23, p = 0.04) EF. We found positive actor (patients B = 0.37 B = 0.13, p = 0.04) and partner (both B = 0.17, p < 0.05) associations for negative DC in patients and partners. Partners' supportive DC was negatively associated with patients (B = -0.31, p = 0.03) and partners' EF (B = -0.34, p = 0.003). CONCLUSIONS: This study highlight the importance of DC (especially from the partners' perspective) for EF in advanced cancer but also identifies differences in the experience of patients and their partners. Future research is needed to understand the mechanisms of such relations and the common and unique support options that may facilitate adjustment in patients with advanced cancer and their partners.
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Neoplasias , Esposos , Adaptación Psicológica , Humanos , Relaciones Interpersonales , Neoplasias/psicología , Neoplasias/terapia , Satisfacción Personal , Calidad de Vida/psicología , Esposos/psicologíaRESUMEN
INTRODUCTION: The COVID-19 outbreak has affected care for non-COVID diseases like cancer. We evaluated the impact of the COVID-19 outbreak on prostate cancer care in the Netherlands. METHODS: Prostate cancer diagnoses per month in 2020-2021 versus 2018-2019 were compared based on preliminary data of the Netherlands Cancer Registry (NCR) and nationwide pathology network. Detailed data was retrieved from the NCR for the cohorts diagnosed from March-May 2020 (first COVID-19 wave) and March-May 2018-2019 (reference). Changes in number of diagnoses, age, disease stage and first-line treatment were compared. RESULTS: An initial decline of 17% in prostate cancer diagnoses during the first COVID-19 wave was observed. From May onwards the number of diagnoses started to restore to approximately 95% of the expected number by the end of 2020. Stage at diagnosis remainedstable over time. In low-risk localised prostate cancer radical prostatectomy was conducted more often in week 9-12 (21% versus 12% in the reference period; OR=1.9, 95% CI; 1.2-3.1) and less active surveillance was applied (67% versus 78%; OR=0.6, 95% CI; 0.4-0.9). In the intermediate-risk group, a similar change was observed in week 13-16. Radical prostatectomy volumes in 2020 were comparable to 2018-2019. CONCLUSION: During the first COVID-19 wave the number of prostate cancer diagnoses declined. In the second half of 2020 this largely restored although the number remained lower than expected. Changes in treatment were temporary and compliant with adapted guidelines. Although delayed diagnoses could result in a less favourable stage distribution, possibly affecting survival, this seems not very likely.
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COVID-19 , Neoplasias de la Próstata , COVID-19/epidemiología , Brotes de Enfermedades , Humanos , Masculino , Países Bajos/epidemiología , Prostatectomía , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapiaRESUMEN
CONTEXT: Palliative care aims to support patients' spiritual needs with the intention of promoting their spiritual well-being (SWB), an important dimension of quality of life. SWB is one of the less-studied dimensions of QoL, particularly in a secular country such as the Netherlands. OBJECTIVES: In this study we aimed to get a better understanding of SWB in Dutch patients with advanced cancer. We therefore examined its prominence and associated factors. METHODS: We used the baseline data of a cohort study on experienced quality of care and quality of life (eQuiPe study), which included 1,103 patients with advanced cancer. In addition to sociodemographic and religious/spiritual characteristics, study measures comprised the SWB subscales Meaning, Peace, and Faith of the revised FACIT-Sp-12, spiritual problems and needs (PNPCsv), quality of life (EORTC-QLQ-C30) and satisfaction with healthcare professionals' interpersonal skills (INPATSAT-32). RESULTS: On average, patients experienced quite a bit of Meaning (8.9, SD 2.3), a little bit to somewhat Peace (6.8, SD 2.7), and very low levels of Faith (2.9, SD 3.7). Two-thirds (71%) of patients reported one or more spiritual problems, for which the majority (54%) wanted to receive attention. In the final multivariable models, only a few factors were associated with SWB, such as greater spiritual needs with lower levels of Meaning and Peace. CONCLUSION: Dutch patients with advanced cancer experience medium to low levels of Meaning, Peace, and Faith. More attention for their SWB is warranted.
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Neoplasias , Calidad de Vida , Estudios de Cohortes , Humanos , Neoplasias/complicaciones , Neoplasias/terapia , Cuidados Paliativos , EspiritualidadRESUMEN
BACKGROUND: The COVID-19 pandemic has disrupted regular health care with potential consequences for non-COVID diseases like cancer. To ensure continuity of oncological care, guidelines were temporarily adapted. OBJECTIVE: To evaluate the impact of the COVID-19 outbreak on bladder cancer care in the Netherlands. METHODS: The number of bladder cancer (BC) diagnoses per month during 2020-2021 was compared to 2018-2019 based on preliminary data from the Netherlands Cancer Registry (NCR). Additionally, detailed data were retrieved from the NCR for the cohort diagnosed between March 1st-May 31st 2020 (first COVID wave) and 2018-2019 (reference cohort). BC diagnoses, changes in age and stage at diagnosis, and time to first-line treatment were compared between both periods. Changes in treatment were evaluated using logistic regression. RESULTS: During the first COVID wave (week 9-22), the number of BC diagnoses decreased by 14%, corresponding with approximately 300 diagnoses, but increased again in the second half of 2020. The decline was most pronounced from week 13 onwards in patients≥70 years and patients with non-muscle invasive BC. Patients with muscle-invasive disease were less likely to undergo a radical cystectomy (RC) in week 17-22 (ORâ=â0.62, 95% CIâ=â0.40-0.97). Shortly after the start of the outbreak, use of neoadjuvant chemotherapy decreased from 34% to 25% but this (non-significant) effect disappeared at the end of April. During the first wave, 5% more RCs were performed compared to previous years. Time from diagnosis to RC became 6 days shorter. Overall, a 7% reduction in RCs was observed in 2020. CONCLUSIONS: The number of BC diagnoses decreased steeply by 14% during the first COVID wave but increased again to pre-COVID levels by the end of 2020 (i.e. 600 diagnoses/month). Treatment-related changes remained limited and followed the adapted guidelines. Surgical volume was not compromised during the first wave. Altogether, the impact of the first COVID-19 outbreak on bladder cancer care in the Netherlands appears to be less pronounced than was reported for other solid tumors, both in the Netherlands and abroad. However, its impact on bladder cancer stage shift and long-term outcomes, as well as later pandemic waves remain so far unexamined.
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Treatment evaluation in metastatic castration-resistant prostate cancer is challenging. There is an urgent need for biomarkers to discriminate short-term survivors from long-term survivors, shortly after treatment initiation. Thereto, the added value of early RNA biomarkers on predicting progression-free survival (PFS) and overall survival (OS) were explored. The RNA biomarkers: KLK3 mRNA, miR-375, miR-3687, and NAALADL2-AS2 were measured in 93 patients with mCRPC, before and 1 month after start of first-line abiraterone acetate or enzalutamide treatment, in two prospective clinical trials. The added value of the biomarkers to standard clinical parameters in predicting PFS and OS was tested by Harell's C-index. To test whether the biomarkers were independent markers of PFS and OS, multivariate Cox regression was used. The best prediction model for PFS and OS was formed by adding miR-375 and KLK3 (at baseline and 1 month) to standard clinical parameters. Baseline miR-375 and detectable KLK3 after 1 month of therapy were independently related to shorter PFS, which was not observed for OS. In conclusion, the addition of KLK3 and miR-375 (at baseline and 1 month) to standard clinical parameters resulted in the best prediction model for survival assessment.
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Background: Intensive end-of-life care (i.e., the overuse of treatments and hospital resources in the last months of life), is undesirable since it has a minimal clinical benefit with a substantial financial burden. The aim was to investigate the care in the last three months of life (end-of-life [EOL]) in castration-resistant prostate cancer (CRPC). Methods: Castration-resistant prostate cancer registry (CAPRI) is an investigator-initiated, observational multicenter cohort study in 20 hospitals retrospectively including patients diagnosed with CRPC between 2010 and 2016. High-intensity care was defined as the initiation of life-prolonging drugs (LPDs) in the last month, continuation of LPD in last 14 days, >1 admission, admission duration ≥14 days, and/or intensive care admission in last three months of life. Descriptive and binary logistic regression analyses were performed. Results: High-intensity care was experienced by 41% of 2429 patients in the EOL period. Multivariable analysis showed that age (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.97-0.99), performance status (OR 0.57, 95% CI 0.33-0.97), time from CRPC to EOL (OR 0.98, 95% CI 0.97-0.98), referral to a medical oncologist (OR 1.99, 95% CI 1.55-2.55), prior LPD treatment (>1 line OR 1.72, 95% CI 1.31-2.28), and opioid use (OR 1.45, 95% CI 1.08-1.95) were significantly associated with high-intensity care. Conclusions: High-intensity care in EOL is not easily justifiable due to high economic cost and little effect on life span, but further research is awaited to give insight in the effect on patients' and their caregivers' quality of life.
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Uso Excesivo de los Servicios de Salud , Neoplasias de la Próstata Resistentes a la Castración , Cuidado Terminal , Humanos , Masculino , Países Bajos , Neoplasias de la Próstata Resistentes a la Castración/terapia , Sistema de Registros , Estudios Retrospectivos , Cuidado Terminal/métodosRESUMEN
PURPOSE: Advance Care Planning (ACP) is positively associated with the quality of care, but its impact on emotional functioning is ambiguous. This study investigated the association between perceptions of ACP involvement and emotional functioning in patients with advanced cancer. METHODS: This study analyzed baseline data of 1,001 patients of the eQuiPe study, a prospective, longitudinal, multicenter, observational study on quality of care and quality of life in patients with advanced cancer in the Netherlands. Patients with metastatic solid cancer were asked to participate between November 2017 and January 2020. Patients' perceptions of ACP involvement were measured by three self-administered statements. Emotional functioning was measured by the EORTC-QLQ-C30. A linear multivariable regression analysis was performed while taking gender, age, migrant background, education, marital status, and symptom burden into account. RESULTS: The majority of patients (87%) reported that they were as much involved as they wanted to be in decisions about their future medical treatment and care. Most patients felt that their relatives (81%) and physicians (75%) were familiar with their preferences for future medical treatment and care. A positive association was found between patients' perceptions of ACP involvement and their emotional functioning (b=0.162, p<0.001, 95%CI[0.095;0.229]) while controlling for relevant confounders. CONCLUSIONS: Perceptions of involvement in ACP are positively associated with emotional functioning in patients with advanced cancer. Future studies are needed to further investigate the effect of ACP on emotional functioning. TRIAL REGISTRATION NUMBER: NTR6584 Date of registration: 30 June 2017 IMPLICATIONS FOR CANCER SURVIVORS: Patients' emotional functioning might improve from routine discussions regarding goals of future care. Therefore, integration of ACP into palliative might be promising.
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Planificación Anticipada de Atención , Neoplasias , Humanos , Neoplasias/terapia , Percepción , Estudios Prospectivos , Calidad de VidaRESUMEN
BACKGROUND: The MINDACT trial showed excellent 5-year distant metastasis-free survival of 94·7% (95% CI 92·5-96·2) in patients with breast cancer of high clinical and low genomic risk who did not receive chemotherapy. We present long-term follow-up results together with an exploratory analysis by age. METHODS: MINDACT was a multicentre, randomised, phase 3 trial done in 112 academic and community hospitals in nine European countries. Patients aged 18-70 years, with histologically confirmed primary invasive breast cancer (stage T1, T2, or operable T3) with up to three positive lymph nodes, no distant metastases, and a WHO performance status of 0-1 were enrolled and their genomic risk (using the MammaPrint 70-gene signature) and clinical risk (using a modified version of Adjuvant! Online) were determined. Patients with low clinical and low genomic risk results did not receive chemotherapy, and patients with high clinical and high genomic risk did receive chemotherapy (mostly anthracycline-based or taxane-based, or a combination thereof). Patients with discordant risk results (ie, patients with high clinical risk but low genomic risk, and those with low clinical risk but high genomic risk) were randomly assigned (1:1) to receive chemotherapy or not based on either the clinical risk or the genomic risk. Randomisation was done centrally and used a minimisation technique that was stratified by institution, risk group, and clinical-pathological characteristics. Treatment allocation was not masked. The primary endpoint was to test whether the distant metastasis-free survival rate at 5 years in patients with high clinical risk and low genomic risk not receiving chemotherapy had a lower boundary of the 95% CI above the predefined non-inferiority boundary of 92%. In the primary test population of patients with high clinical risk and low genomic risk who adhered to the treatment allocation of no chemotherapy and had no change in risk post-enrolment. Here, we present updated follow-up as well as an exploratory analysis of a potential age effect (≤50 years vs >50 years) and an analysis by nodal status for patients with hormone receptor-positive and HER2-negative disease. These analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT00433589, and the European Clinical Trials database, EudraCT2005-002625-31. Recruitment is complete and further long-term follow-up is ongoing. FINDINGS: Between Feb 8, 2007, and July 11, 2011, 6693 patients were enrolled. On Feb 26, 2020, median follow-up was 8·7 years (IQR 7·8-9·7). The updated 5-year distant metastasis-free survival rate for patients with high clinical risk and low genomic risk receiving no chemotherapy (primary test population, n=644) was 95·1% (95% CI 93·1-96·6), which is above the predefined non-inferiority boundary of 92%, supporting the previous analysis and proving MINDACT as a positive de-escalation trial. Patients with high clinical risk and low genomic risk were randomly assigned to receive chemotherapy (n=749) or not (n=748); this was the intention-to-treat population. The 8-year estimates for distant metastasis-free survival in the intention-to-treat population were 92·0% (95% CI 89·6-93·8) for chemotherapy versus 89·4% (86·8-91·5) for no chemotherapy (hazard ratio 0·66; 95% CI 0·48-0·92). An exploratory analysis confined to the subset of patients with hormone receptor-positive, HER2-negative disease (1358 [90.7%] of 1497 randomly assigned patients, of whom 676 received chemotherapy and 682 did not) shows different effects of chemotherapy administration on 8-year distant metastasis-free survival according to age: 93·6% (95% CI 89·3-96·3) with chemotherapy versus 88·6% (83·5-92·3) without chemotherapy in 464 women aged 50 years or younger (absolute difference 5·0 percentage points [SE 2·8, 95% CI -0·5 to 10·4]) and 90·2% (86·8-92·7) versus 90·0% (86·6-92·6) in 894 women older than 50 years (absolute difference 0·2 percentage points [2·1, -4·0 to 4·4]). The 8-year distant metastasis-free survival in the exploratory analysis by nodal status in these patients was 91·7% (95% CI 88·1-94·3) with chemotherapy and 89·2% (85·2-92·2) without chemotherapy in 699 node-negative patients (absolute difference 2·5 percentage points [SE 2·3, 95% CI -2·1 to 7·2]) and 91·2% (87·2-94·0) versus 89·9% (85·8-92·8) for 658 patients with one to three positive nodes (absolute difference 1·3 percentage points [2·4, -3·5 to 6·1]). INTERPRETATION: With a more mature follow-up approaching 9 years, the 70-gene signature shows an intact ability of identifying among women with high clinical risk, a subgroup, namely patients with a low genomic risk, with an excellent distant metastasis-free survival when treated with endocrine therapy alone. For these women the magnitude of the benefit from adding chemotherapy to endocrine therapy remains small (2·6 percentage points) and is not enhanced by nodal positivity. However, in an underpowered exploratory analysis this benefit appears to be age-dependent, as it is only seen in women younger than 50 years where it reaches a clinically relevant threshold of 5 percentage points. Although, possibly due to chemotherapy-induced ovarian function suppression, it should be part of informed, shared decision making. Further study is needed in younger women, who might need reinforced endocrine therapy to forego chemotherapy. FUNDING: European Commission Sixth Framework Programme.
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Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Transcriptoma/genética , Adolescente , Adulto , Factores de Edad , Anciano , Antraciclinas/administración & dosificación , Neoplasias de la Mama/patología , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Taxoides/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
Circulating RNAs extracted from liquid biopsies represent a promising source of cancer- and therapy-related biomarkers. We screened whole blood from patients with metastatic castration-resistant prostate cancer (mCRPC) following their first-line treatment with abiraterone acetate and prednisone (AA-P) to identify circulating RNAs that may correlate with progression-free survival (PFS). In a prospective multicenter observational study, 53 patients with mCRPC were included after they started first-line AA-P treatment. Blood was drawn at baseline, 1, 3, and 6 months after treatment initiation. The levels of predefined circulating RNAs earlier identified as being upregulated in patients with mCRPC (e.g., microRNAs, long noncoding RNAs, and mRNAs), were analyzed. Uni- and multivariable Cox regression and Kaplan-Meier analyses were used to analyze the prognostic value of the various circulating RNAs for PFS along treatment. Detectable levels of kallikrein-related peptidase 3 (KLK3) mRNA at baseline were demonstrated to be an independent prognostic marker for PFS (201 vs 501 days, P = 0.00054). Three months after AA-P treatment initiation, KLK3 could not be detected in the blood of responding patients, but was still detectable in 56% of the patients with early progression. Our study confirmed that KLK3 mRNA detection in whole blood is an independent prognostic marker in mCRPC patients receiving AA-P treatment. Furthermore, the levels of circulating KLK3 mRNA in patients receiving AA-P treatment might reflect treatment response or early signs of progression.
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Acetato de Abiraterona/uso terapéutico , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/sangre , Calicreínas/genética , Biopsia Líquida/métodos , Metástasis de la Neoplasia , Prednisona/uso terapéutico , Antígeno Prostático Específico/genética , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , ARN Mensajero/sangre , Acetato de Abiraterona/administración & dosificación , Adulto , Anciano , Antineoplásicos/administración & dosificación , Estudios de Casos y Controles , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Pronóstico , Estudios Prospectivos , Neoplasias de la Próstata Resistentes a la Castración/genética , Resultado del TratamientoRESUMEN
AIM: Sunitinib is an oral tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST). Because of the large interpatient pharmacokinetic variability and established exposure-response and exposure-toxicity relationships in clinical trial patients, therapeutic drug monitoring (TDM) seems promising for optimizing sunitinib exposure. We aimed to investigate the relationship between sunitinib exposure and treatment outcome in a real-world patient cohort. METHODS: We performed a retrospective observational cohort study in 53 patients with metastatic RCC and 18 patients with metastatic GIST treated with sunitinib and receiving TDM-guided dosing. Time on treatment - as a surrogate for progression-free survival - in patients who achieved adequate sunitinib exposure was compared with patients who did not. Additionaly, the median sunitinib exposure was compared in patients with or without sunitinib-induced toxicity leading to dose reduction. RESULTS: The median time on treatment in patients with RCC who achieved adequate sunitinib exposure (n = 39) was 32 weeks, compared to 15 weeks in patients who did not achieve adequate sunitinib exposure (n = 12) (P = 0.244). In 29 patients (41%) with toxicity leading to dose reduction, sunitinib sum plasma trough concentration (Ctrough ) until dose reduction was significantly higher compared to patients without toxicity leading to dose reduction (median 60 ng/mL vs 44 ng/mL; P < 0.001) and reduced to comparable levels after dose reduction (44 ng/mL; P = 0.488). CONCLUSION: In our real-world patient cohort, patients with sunitinib-induced toxicity requiring dose reduction had significantly higher sunitinib exposure compared to patients without toxicity. The threshold for toxicity, however, was lower compared to that previously described in clinical trials.
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Antineoplásicos , Carcinoma de Células Renales , Tumores del Estroma Gastrointestinal , Neoplasias Renales , Antineoplásicos/efectos adversos , Carcinoma de Células Renales/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Humanos , Indoles/efectos adversos , Neoplasias Renales/tratamiento farmacológico , Pirroles/efectos adversos , Estudios Retrospectivos , Sunitinib/uso terapéutico , Resultado del TratamientoRESUMEN
PURPOSE: Patients with testicular germ cell tumor (TGCT) are at increased risk of developing a contralateral TGCT (CTGCT). Although some studies suggest that prior treatment with platinum-based chemotherapy affects CTGCT risk, a relationship between CTGCT risk and platinum dose has not previously been assessed. We analyzed the association between the number of platinum-based chemotherapy cycles and CTGCT risk. PATIENTS AND METHODS: The risk of developing a metachronous CTGCT was evaluated in a nationwide cohort of 4,755 patients diagnosed with primary TGCT in the Netherlands between 1989 and 2007. Standardized incidence ratios were computed to compare CTGCT incidence with expected TGCT on the basis of TGCT incidence in the general population. The cumulative incidence of CTGCT was estimated in the presence of death as competing risk. The effect of treatment with platinum-based chemotherapy on CTGCT risk was assessed using multivariable Cox proportional hazards regression models. RESULTS: CTGCT was diagnosed in 136 patients (standardized incidence ratio, 14.6; 95% CI, 12.2 to 17.2). The cumulative incidence increased up to 20 years after primary diagnosis, reaching 3.4% (95% CI, 2.8% to 4.0%) after 20 years of follow up. The risk of developing a CTGCT decreased with age (hazard ratio [HR], 0.93; 95% CI, 0.90 to 0.96), was lower after nonseminomatous germ cell tumor (HR, 0.58; 95% CI, 0.35 to 0.96) and decreased with every additional cycle of chemotherapy (HRper cycle, 0.74; 95% CI, 0.64 to 0.85). CONCLUSION: Approximately one in every 30 survivors of TGCT will develop a CTGCT, with CTGCT incidence increasing up to 20 years after a primary TGCT. Treatment with platinum-based chemotherapy shows a dose-dependent inverse association with CTGCT risk.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias Primarias Secundarias/epidemiología , Compuestos Organoplatinos/administración & dosificación , Neoplasias Testiculares/tratamiento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Primarias Secundarias/inducido químicamente , Neoplasias Primarias Secundarias/patología , Países Bajos/epidemiología , Compuestos Organoplatinos/efectos adversos , Pronóstico , Factores de Riesgo , Neoplasias Testiculares/patologíaRESUMEN
BACKGROUND: With the introduction of new therapeutic options, the landscape of metastatic bladder cancer (mBC) management is shifting. We describe current clinical practice and outcomes of mBC patients as a benchmark for translation of developments into clinical practice in the near future. PATIENTS AND METHODS: Nation-wide population-based cohort study including all patients diagnosed with synchronous metastatic bladder cancer in the Netherlands in 2016-2017, identified through the Netherlands Cancer Registry (NCR). Clinical data on patient and disease characteristics, treatments and survival from the NCR were supplemented with specific information from electronic health records and descriptively analyzed. This study was part of the Prospective Bladder Cancer Infrastructure. RESULTS: Synchronous metastatic bladder cancer was diagnosed in 636 patients in the Netherlands in 2016 and 2017. 35% (221 patients) received systemic treatment, of whom 88 received multiple treatment lines. Most common first-line regimen was carboplatin-based chemotherapy (49%), followed by cisplatin-based chemotherapy (41%) and immunotherapy (8%). Factors associated with systemic treatment were: young age, <2 comorbidities, adequate renal function and performance-status (WHO-0-1/Karnofsky-80-100), urothelial carcinoma and lymph node only metastases. Median overall survival was 4.4 months for the total cohort, and 12.3, 12.9 and 11.1 months for patients treated with first-line immunotherapy, cisplatin-based and carboplatin-based chemotherapy, respectively. CONCLUSIONS: Many mBC patients received no systemic treatment or received carboplatin-based chemotherapy, partly because of cisplatin-ineligibility. Observed survival corresponded relatively well with rates reported from trials among chemotherapy-treated patients. These data can serve as a benchmark for future studies evaluating the application of immunotherapy outside a trial setting.