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1.
Acta Oncol ; 63: 28-34, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38353407

RESUMO

BACKGROUND: This study compares the characteristics, referral and treatment patterns and overall survival (OS) of gastrointestinal stromal tumor (GIST) patients treated in reference and non-reference centers in the Netherlands. PATIENTS AND METHODS: This retrospective cohort study on patients diagnosed between 2016 and 2019, utilises data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Database. Patients were categorized into two groups: patients diagnosed in or referred to reference centers and patients diagnosed in non-reference centers without referral. RESULTS: This study included 1,550 GIST patients with a median age of 67.0 in reference and 68.0 years in non-reference centers. Eighty-seven per cent of patients were diagnosed in non-reference centers, of which 36.5% (493/1,352) were referred to a reference center. Referral rates were higher for high-risk (62.2% [74/119]) and metastatic patients (67.2% [90/134]). Mutation analysis was performed in 96.9% and 87.6% of these cases in reference and in non-reference centers (p < 0.01), respectively. Systemic therapy was given in reference centers versus non-reference in 89.5% versus 82.0% (p < 0.01) of high-risk and in 94.1% versus 65.9% (p < 0.01) of metastatic patients, respectively. The proportion of positive resection margins and tumor rupture did not differ between reference and non-reference centers. Median OS was not reached. CONCLUSION: A substantial amount of metastatic GIST patients in non-reference centers did not receive systemic treatment. This might be due to valid reasons. However, optimisation of the referral strategy of GIST patients in the Netherlands could benefit patients. Further research is needed to explore reasons for not starting systemic treatment in metastatic GIST patients.


Assuntos
Antineoplásicos , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Humanos , Tumores do Estroma Gastrointestinal/terapia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Antineoplásicos/uso terapêutico , Estudos Retrospectivos , Encaminhamento e Consulta , Países Baixos/epidemiologia , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/terapia
2.
Support Care Cancer ; 32(5): 324, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700723

RESUMO

PURPOSE: To identify elements of timely integration of palliative care (PC) into hospital oncology care from best practices. Thereafter, to assess the level of consensus among oncology and PC specialists and patient and relative representatives on the characteristics of timely integration of PC. METHODS: A three-round modified Delphi study was conducted. The expert panel consisted of 83 healthcare professionals (HCPs) from 21 Dutch hospitals (43 physicians, 40 nurses), 6 patient and 2 relative representatives. In the first round, four elements of integrated PC were considered: (1) identification of potential PC needs, (2) advance care planning (ACP), (3) routine symptom monitoring and (4) involvement of the specialist palliative care team (SPCT). In subsequent rounds, the panellists assessed which characteristics were triggers for initiating an element. A priori consensus was set at ≥ 70%. RESULTS: A total of 71 (78%) panellists completed the first questionnaire, 65 (71%) the second and 49 (54%) the third. Panellists agreed that all patients with incurable cancer should have their PC needs assessed (97%), symptoms monitored (91%) and ACP initiated (86%). The SPCT should be involved at the patient's request (86%) or when patients suffer from increased symptom burden on multiple dimensions (76%). Patients with a life expectancy of less than 3 months should be offered a consultation (71%). CONCLUSION: The expert panel agreed that timely integration of PC into oncology is important for all patients with incurable cancer, using early identification, ACP and routine symptom monitoring. Involvement of the SPCT is particularly needed in patients with multidimensional symptom burden and in those nearing death.


Assuntos
Técnica Delphi , Neoplasias , Cuidados Paliativos , Humanos , Cuidados Paliativos/métodos , Cuidados Paliativos/organização & administração , Neoplasias/terapia , Masculino , Países Baixos , Feminino , Pessoa de Meia-Idade , Inquéritos e Questionários , Planejamento Antecipado de Cuidados/organização & administração , Adulto , Prestação Integrada de Cuidados de Saúde/organização & administração , Prestação Integrada de Cuidados de Saúde/métodos , Consenso , Fatores de Tempo , Equipe de Assistência ao Paciente/organização & administração
3.
Support Care Cancer ; 32(5): 279, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38594390

RESUMO

PURPOSE: This study aims to (1) explore the prevalence of patient-reported financial difficulties among GIST patients, differentiating between those currently undergoing tyrosine kinase inhibitor (TKI) treatment and those who are not; (2) investigate associations between financial difficulties and sociodemographic and clinical characteristics, work, cancer-related concerns, anxiety and depression and (3) study the impact of financial difficulties on health-related quality of life. METHODS: A cross-sectional study was conducted among Dutch GIST patients diagnosed between 2008 and 2018, who were invited to complete a one-time survey between September 2020 and June 2021. Patients completed nine items of the EORTC item bank regarding financial difficulties, seven work-related questions, the Hospital Anxiety and Depression Scale, Cancer Worry Scale and EORTC QLQ-C30. RESULTS: In total, 328 GIST patients participated (response rate 63.0%), of which 110 (33.8%) were on TKI treatment. Patients currently treated with TKIs reported significantly more financial difficulties compared to patients not on TKIs (17.3% vs 8.7%, p = 0.03). The odds of experiencing financial difficulties was 18.9 (95% CI 1.7-214.7, p = 0.02) times higher in patients who were less able to work due to their GIST diagnosis. Patients who experienced financial difficulties had significantly lower global quality of life and functioning, and more frequently reported psychological symptoms as compared to patients who did not report financial difficulties. CONCLUSION: Even in a country where the costs of TKIs and follow-up care are covered by health insurance, financial difficulties can be present in GIST patients, especially in patients on TKI treatment, and may negatively influence the quality of life.


Assuntos
Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Humanos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/epidemiologia , Estudos Transversais , Qualidade de Vida , Países Baixos/epidemiologia , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias Gastrointestinais/patologia
4.
Int J Gynecol Cancer ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38909994

RESUMO

BACKGROUND: Vulvar squamous cell carcinoma (VSCC) is a rare cancer for which the cornerstone of treatment is surgery with high complication rates. The unmet need is a less radical and more effective treatment for VSCC. PRIMARY OBJECTIVES: To investigate the impact of mono-immunotherapy pembrolizumab as neoadjuvant treatment for primary resectable VSCC patients. STUDY HYPOTHESIS: Some primary VSCC patients display a specific immune profile which is associated with better survival. In other tumors, this profile is associated with a better response to programmed cell death protein 1 (PD-1) checkpoint blockade which may reinvigorate tumor-specific T cells. This potentially results in a reduced tumor load and less radical surgery and/or adjuvant treatment in patients with this immune profile. TRIAL DESIGN: This is an investigator-initiated, prospective, single arm, multicenter, phase II clinical trial. INCLUSION CRITERIA: Patients with VSCC clinical stage International Federation of Gynecology and Obstetrics (FIGO) I-III (2021) eligible for primary surgery, with at least one measurable lesion of at least one dimension ≥10 mm in the largest diameter, are included in this study. MAIN EXCLUSION CRITERIA: Patients not suitable for surgery and/or previously treated with immunomodulatory agents, and/or who suffer from comorbidities that may interfere with PD-1 blockade, are excluded from the study. ENDPOINTS: The clinical efficacy of neoadjuvant pembrolizumab in VSCC is measured by an objective change in tumor size according to the Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) and documented by calipers using standardized digital photography with a reference ruler. In addition, the activation, proliferation, and migration of T cells in the tumor will be studied. The secondary endpoints are pathological complete responses at the time of surgery, feasibility, and safety. SAMPLE SIZE: 40 patients with FIGO I-III (2021) primary VSCC will be enrolled. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The intervention phase started in July 2023 and will continue until July 2025. The expected completion of the entire study is July 2026. TRIAL REGISTRATION NUMBER: NCT05761132.

5.
Acta Oncol ; 62(12): 1616-1624, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37856077

RESUMO

BACKGROUND: There are two main coping styles regarding information seeking under medical threat; monitoring (information-seeking) and blunting (information-avoiding). The aim of this study is to (1) determine factors associated with a monitoring or blunting coping style in gastro-intestinal stromal tumour (GIST) patients and (2) investigate its association with psychological distress, cancer-related concerns, health-related quality of life and satisfaction with healthcare. METHODS: In a cross-sectional study, Dutch GIST patients completed the shortened version of the Threatening Medical Situations Inventory to determine their coping style, the Hospital Anxiety and Depression Scale, Cancer Worry Scale, EORTC QLQ-C30 and part of the EORTC QLQ-INFO25. RESULTS: A total of 307 patients were classified as blunters (n = 175, 57%) or monitors (n = 132, 43%). Coping style was not associated with tumour or treatment variables, but being a female (OR 2.5; 95%CI 1.5-4.1; p= <.001) and higher educated (OR 5.5; 95%CI 2.5-11.9, p= <.001) were associated with higher odds of being a monitor. Monitors scored significantly lower on emotional functioning (mean = 86.8 vs mean = 90.9, p=.044), which is considered a trivial difference, more often experienced severe fear of cancer recurrence or progression (53.0% vs 37.7%, p=.007), and had more concerns about dying from GIST in the future (60.6% vs 47.4%, p=.025). Compared to blunters, monitors were less satisfied with the received healthcare and information, and would have liked to receive more information. CONCLUSION: GIST patients with a monitoring coping style experience a higher emotional burden. Additionally, monitors exhibit a greater need for information. Although this need for information could potentially result in fears and concerns, recognising it may also create an opening for tailored communication and information.


Assuntos
Tumores do Estroma Gastrointestinal , Angústia Psicológica , Humanos , Feminino , Qualidade de Vida , Estudos Transversais , Satisfação do Paciente , Recidiva Local de Neoplasia , Adaptação Psicológica , Satisfação Pessoal
6.
Palliat Support Care ; 21(4): 616-627, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36177886

RESUMO

OBJECTIVES: It is widely acknowledged that co-occurring symptoms in patients with a psychosocial and spiritual aspects should also be considered. However, this multidimensional approach is difficult to integrate into daily practice, especially for generalist clinicians not specialized in palliative care. We aimed to identify the barriers and facilitators to multidimensional symptom management. METHODS: Focus group meetings were conducted with the following stakeholders: (1) patient representatives, (2) generalist community nurses, (3) generalist hospital nurses, (4) general practitioners, (5) generalist hospital physicians, and (6) palliative care specialists. Audiotapes were transcribed verbatim and thematically analyzed. RESULTS: Fifty-one participants (6-12 per group) reported barriers and facilitators with 3 main themes: multidimensional symptom assessment, initiating management of nonphysical problems, and multidisciplinary collaboration. As barriers, generalist clinicians and palliative care specialists reported that generalist clinicians often lack the communication skills to address nonphysical problems and are unaware of available resources for multidimensional symptom management. Palliative care specialists felt that generalist clinicians may be unaware that assessing nonphysical problems is important and focus on pharmacological interventions. Generalist nurses and palliative care specialists indicated that hierarchical difficulties between them and generalist physicians are barriers to multidisciplinary collaboration. Reported facilitators included using symptom assessment scales and standardized questions on nonphysical problems. SIGNIFICANCE OF RESULTS: Generalist clinicians can be supported by improving their communication skills, increasing their awareness of available resources for multidimensional symptom management, and by using a standardized approach to assess all 4 dimensions of palliative care.


Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Cuidados Paliativos , Humanos , Cuidados Paliativos/métodos , Grupos Focais , Defesa do Paciente
7.
BMC Cancer ; 22(1): 247, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247992

RESUMO

BACKGROUND: Effective systemic treatments have revolutionized the management of patients with metastatic melanoma, including those with brain metastases. The extent to which these treatments influence disease trajectories close to death is unknown. Therefore, this study aimed to gain insight into provided treatments and healthcare consumption during the last 3 months of life in patients with melanoma brain metastases. METHODS: Retrospective, single-center study, including consecutive patients with melanoma brain metastases diagnosed between June-2015 and June-2018, referred to the medical oncologist, and died before November-2019. Patient and tumor characteristics, anti-tumor treatments, healthcare consumption, presence of neurological symptoms, and do-not-resuscitate status were extracted from medical charts. RESULTS: 100 patients were included. A BRAF-mutation was present in 66 patients. Systemic anti-tumor therapy was given to 72% of patients during the last 3 months of life, 34% in the last month, and 6% in the last week. Patients with a BRAF-mutation more frequently received systemic treatment during the last 3 (85% vs. 47%) and last month (42% vs. 18%) of life than patients without a BRAF-mutation. Furthermore, patients receiving systemic treatment were more likely to visit the emergency room (ER, 75% vs. 36%) and be hospitalized (75% vs. 36%) than those who did not. CONCLUSION: The majority of patients with melanoma brain metastases received anti-tumor treatment during the last 3 months of life. ER visits and hospitalizations occurred more often in patients on anti-tumor treatment. Further research is warranted to examine the impact of anti-tumor treatments close to death on symptom burden and care satisfaction.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Melanoma/tratamento farmacológico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Assistência Terminal/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Serviços Médicos de Emergência/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Melanoma/genética , Melanoma/patologia , Pessoa de Meia-Idade , Mutação , Países Baixos , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Resultado do Tratamento
8.
BMC Cancer ; 22(1): 511, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524239

RESUMO

BACKGROUND: Acquired resistance to approved tyrosine kinase inhibitors limits their clinical use in patients with gastrointestinal stromal tumor (GIST). This study investigated the safety, tolerability and efficacy of alpelisib, a phosphatidylinositol 3-kinase inhibitor, used in combination with imatinib in patients with advanced GIST who had failed prior therapy with both imatinib and sunitinib. METHODS: This phase 1b, multicenter, open-label study consisted of 2 phases: dose escalation and dose expansion. Dose escalation involved 200 mg once daily (QD) alpelisib, initially, followed by 250 and 350 mg. These were combined with 400 mg QD imatinib until maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) of alpelisib in combination with imatinib was determined. This MTD/RP2D dose was tested to evaluate the clinical activity of this combination in dose expansion. RESULTS: Fifty-six patients were enrolled, 21 and 35 in the dose escalation and expansion phases, respectively. The MTD of alpelisib given with imatinib was determined as 350 mg QD. Combination treatment showed partial response in 1 (2.9%) and stable disease in 15 (42.9%) patients. Median progression-free survival was 2 months (95% CI 1.8-4.6). Overall, 92.9% patients had adverse events (AEs) while 46.4% had grade 3/4 AEs, hyperglycemia being the most common (23.2%). CONCLUSIONS: The MTD of alpelisib was estimated as 350 mg QD when used in combination with imatinib 400 mg QD after oral administration in patients with advanced GIST. The safety and tolerability profile of this combination was acceptable; however, the combination did not demonstrate sufficient clinical activity to justify additional clinical testing. TRIAL REGISTRATION: ClinicalTrials.gov NCT01735968 (date of initial registration 28/11/2012).


Assuntos
Tumores do Estroma Gastrointestinal , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Tiazóis , Resultado do Tratamento
9.
Gynecol Oncol ; 166(1): 148-153, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35644730

RESUMO

OBJECTIVE: Patients with advanced ovarian cancer have a poor prognosis and can experience debilitating symptoms in the last phase of life. Several analyses, mainly performed in the United States (US), show high rates of chemotherapy administration and hospital visits near the end-of-life in this patient category. No large European studies are available, while the organisation of palliative care differs between the US and Europe. We aimed to analyse the intensity of inpatient care near the end-of-life in the Netherlands and perform a cross-study comparison with previous reports. METHODS: All patients with ovarian cancer that died in 2016 and 2017 were identified from the Vektis database, a data warehouse including all insurance declarations in the Netherlands. For the last 6 months of life the following parameters of aggressive care were extracted: administration of chemotherapy, emergency room (ER) visits, surgical procedures, hospital and intensive care unit (ICU) admissions. The intensity of inpatient care was compared to previously reported European and US data. RESULTS: Data on medical care use was available for 1775 patients. During the last 6 months of life, half of the ovarian cancer patients were admitted to hospital. Chemotherapy administration near the end-of-life was infrequent: 12% in the last month of life. Surgery and ICU admissions in the final 6 months of life were rare (<10%). Our cohort showed the lowest percentages of all five indicators of aggressive care reported thus far. CONCLUSION: Aggressive medical care use in the final 6 months of life in this Dutch cohort of ovarian cancer patients was lower than in other previously reported cohorts.


Assuntos
Neoplasias Ovarianas , Assistência Terminal , Carcinoma Epitelial do Ovário , Morte , Feminino , Humanos , Países Baixos/epidemiologia , Neoplasias Ovarianas/terapia , Sistema de Registros , Estudos Retrospectivos , Assistência Terminal/métodos , Estados Unidos/epidemiologia
10.
Support Care Cancer ; 30(3): 2307-2315, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34727226

RESUMO

CONTEXT: Taste, smell, and mouthfeel disturbances are underrated and underreported, but important side effects of anti-cancer medication. These symptoms are associated with a lower quality of life (QoL). The prevalence and the impact of taste, smell, and mouthfeel disturbances on daily life in patients with a gastrointestinal stromal tumor (GIST) are largely unknown. OBJECTIVES: This exploratory study assessed the prevalence and type of taste, smell, and mouthfeel disturbances and their impact on daily life and QoL in patients with a GIST treated with a tyrosine-kinase inhibitor (TKI). METHODS: Patients currently treated with TKIs for GIST completed a standardized questionnaire. The questionnaire addressed changes in taste, smell, and mouthfeel and, if changes occurred, impact on daily life and QoL. Statistics are descriptive. RESULTS: A total of 65 GIST patients on TKI treatment completed the questionnaire. Of these patients, 79%, 12%, and 9% currently used imatinib, sunitinib, and regorafenib respectively. Taste, smell, and mouthfeel disturbances were reported by 25 (38%), 15 (23%), and 36 (55%) patients respectively. Salty and sweet tastes were mostly affected, respectively in 14 and 13 patients. A dry mouth was experienced by 29 (45%) patients. Taste disturbances were more often reported to have impact on daily life and QoL (80% and 60%) than smell (47% and 31%) and mouthfeel disturbances (47% and 30%). CONCLUSION: Taste, smell, and mouthfeel disturbances are frequent side effects of TKIs in GIST patients. Daily life and QoL are affected in a considerable number of those patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NL7827 (2019-06-25).


Assuntos
Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Inibidores de Proteínas Quinases/efeitos adversos , Qualidade de Vida , Olfato , Paladar , Tirosina
11.
Support Care Cancer ; 30(6): 5137-5146, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35233640

RESUMO

PURPOSE: Treatment with the tyrosine kinase inhibitor (TKI) imatinib in patients with gastrointestinal stromal tumours (GIST) causes symptoms that could negatively impact health-related quality of life (HRQoL). Treatment-related symptoms are usually clinician-reported and little is known about patient reports. We used survey and online patient forum data to investigate (1) prevalence of patient-reported symptoms; (2) coverage of symptoms mentioned on the forum by existing HRQoL questionnaires; and (3) priorities of prevalent symptoms in HRQoL assessment. METHODS: In the cross-sectional population-based survey study, Dutch GIST patients completed items from the EORTC QLQ-C30 and Symptom-Based Questionnaire (SBQ). In the forum study, machine learning algorithms were used to extract TKI side-effects from English messages on an international online forum for GIST patients. Prevalence of symptoms related to imatinib treatment in both sources was calculated and exploratively compared. RESULTS: Fatigue and muscle pain or cramps were reported most frequently. Seven out of 10 most reported symptoms (i.e. fatigue, muscle pain or cramps, facial swelling, joint pain, skin problems, diarrhoea, and oedema) overlapped between the two sources. Alopecia was frequently mentioned on the forum, but not in the survey. Four out of 10 most reported symptoms on the online forum are covered by the EORTC QLQ-C30. The EORTC-SBQ and EORTC Item Library cover 9 and 10 symptoms, respectively. CONCLUSION: This first overview of patient-reported imatinib-related symptoms from two data sources helps to determine coverage of items in existing questionnaires, and prioritize HRQoL issues. Combining cancer-generic instruments with treatment-specific item lists will improve future HRQoL assessment in care and research in GIST patients using TKI.


Assuntos
Tumores do Estroma Gastrointestinal , Estudos Transversais , Fadiga/epidemiologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Mesilato de Imatinib/efeitos adversos , Cãibra Muscular , Inibidores de Proteínas Quinases/efeitos adversos , Qualidade de Vida , Inquéritos e Questionários
12.
BMC Palliat Care ; 21(1): 51, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413862

RESUMO

BACKGROUND: A high percentage of people dying at home, and a low percentage of people being admitted to hospital and dying there are regarded as indicators of appropriate care at the end of life. However, performance standards for these quality indicators are often lacking, which makes it difficult to state whether an indicator score falls between the ranges of good or poor quality care. The aim of this study was to assess quality indicators concerning place of death and hospital care utilization in people with diseases relevant for palliative care, and to establish best practice performance standards based on indicator scores in 31 regions in the Netherlands. METHODS: A retrospective nationwide population-based observational study was conducted, using routinely collected administrative data concerning persons who died in 2017 in the Netherlands with underlying causes relevant for palliative care (N = 109,707). Data from four registries were linked for analysis. Scores on eight quality indicators concerning place of death and hospital care utilization were calculated, and compared across 31 healthcare insurance regions to establish relative benchmarks. RESULTS: On average, 36.4% of the study population died at home (range between regions 30.5%-42.6%) and 20.4% in hospital (range 16.6%-25.5%). Roughly half of the population who received hospital care at any time in the last year of life were found to (also) receive hospital care in the last month of life. In the last month, 32.0% of the study population were admitted to hospital (range 29.4-36.4%), 5.3% to an Intensive Care Unit (range 3.2-6.9%) and 23.9% visited an Emergency Department (range 21.0-27.4%). In the same time period, less than 1% of the study population was resuscitated in hospital or received tube or intravenous feeding in hospital. CONCLUSIONS: The variation between regions points towards opportunities for practice improvement. The best practice performance standards as set in this study serve as ambitious but attainable targets for those regions that currently do not meet the standards. Policymakers, healthcare providers and researchers can use the suggested performance standards to further analyze causes of variance between regions and develop and test interventions that can improve practice.


Assuntos
Assistência Terminal , Morte , Humanos , Cuidados Paliativos , Estudos Retrospectivos
13.
Gynecol Obstet Invest ; 87(6): 389-397, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36450222

RESUMO

OBJECTIVES: Ovarian cancer has the worst overall survival rate of all gynecologic malignancies. For the majority of patients, the 5-year overall survival rate of less than 50% has hardly improved over the last decades. To improve the outcome of patients with all subtypes of ovarian cancer, large-scale fundamental and translational research is needed. To accommodate these types of ovarian cancer research, we have established a Dutch nationwide, interdisciplinary infrastructure and biobank: the Archipelago of Ovarian Cancer Research (AOCR). The AOCR will facilitate fundamental and translational ovarian cancer research and enhance interdisciplinary, national, and international collaboration. DESIGN: The AOCR biobank is a prospective ovarian cancer biobank in which biomaterials are collected, processed, and stored in a uniform matter for future (genetic) scientific research. All 19 Dutch hospitals in which ovarian cancer surgery is performed participate and collaborate in the AOCR biobank. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients of 16 years and older with suspected or diagnosed ovarian, fallopian tube, or primary peritoneal cancer are recruited for participation. Patients who agree to participate give written informed consent for collection, storage, and issue of their biomaterials for future studies. After inclusion, different blood samples are taken at various predefined time points both before and during treatment. In case of a diagnostic paracentesis or biopsy, the residual biomaterials of these procedures are stored in the biobank. During surgery, primary tumor tissue and, if applicable, tissue from metastatic sites are collected and stored. From each patient, a representative histological hematoxylin and eosin stained slide is digitalized for research purposes, including reassessment by a panel of gynecologic pathologists. Clinical and pathological data are obtained on a per-study basis from Dutch registries. Research proposals for the issue of biomaterials and data are evaluated by both the Archipelago Scientific Committee and the Steering Committee. Researchers using the biomaterials from the AOCR biobank are encouraged to enrich the biobank with data and materials resulting from their analyses and experiments. LIMITATIONS: The implementation and first 4 years of collection are financed by an infrastructural grant from the Dutch Cancer Society. Therefore, the main limitation is that the costs for sustaining the biobank after the funding period will have to be covered. This coverage will come from incorporation of budget for biobanking in future grant applications and from fees from external researchers and commercial parties using the biomaterials stored in the AOCR biobank. Moreover, we will apply for grants aimed at sustaining and improving research infrastructures and biobanks. CONCLUSIONS: With the establishment of the Dutch nationwide, interdisciplinary Archipelago of Ovarian Cancer Research infrastructure and biobank, fundamental and translational research on ovarian cancer can be greatly improved. The ultimate aim of this infrastructure is that it will lead to improved diagnostics, treatment, and survival of patients with ovarian cancer.


Assuntos
Bancos de Espécimes Biológicos , Neoplasias Ovarianas , Humanos , Feminino , Pesquisa Translacional Biomédica , Estudos Prospectivos , Neoplasias Ovarianas/cirurgia
14.
Cancer Metastasis Rev ; 39(3): 999-1013, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32367253

RESUMO

Response evaluation for cancer treatment consists primarily of clinical and radiological assessments. In addition, a limited number of serum biomarkers that assess treatment response are available for a small subset of malignancies. Through recent technological innovations, new methods for measuring tumor burden and treatment response are becoming available. By utilization of highly sensitive techniques, tumor-specific mutations in circulating DNA can be detected and circulating tumor DNA (ctDNA) can be quantified. These so-called liquid biopsies provide both molecular information about the genomic composition of the tumor and opportunities to evaluate tumor response during therapy. Quantification of tumor-specific mutations in plasma correlates well with tumor burden. Moreover, with liquid biopsies, it is also possible to detect mutations causing secondary resistance during treatment. This review focuses on the clinical utility of ctDNA as a response and follow-up marker in patients with non-small cell lung cancer, melanoma, colorectal cancer, and breast cancer. Relevant studies were retrieved from a literature search using PubMed database. An overview of the available literature is provided and the relevance of ctDNA as a response marker in anti-cancer therapy for clinical practice is discussed. We conclude that the use of plasma-derived ctDNA is a promising tool for treatment decision-making based on predictive testing, detection of resistance mechanisms, and monitoring tumor response. Necessary steps for translation to daily practice and future perspectives are discussed.


Assuntos
DNA Tumoral Circulante/sangue , Neoplasias/genética , Neoplasias/terapia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Humanos , Biópsia Líquida , Mutação , Neoplasias/sangue , Neoplasias/patologia , Valor Preditivo dos Testes
15.
Support Care Cancer ; 29(10): 5691-5699, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33629188

RESUMO

PURPOSE: Taste and smell alterations (TAs and SAs) are often reported by patients with cancer receiving systemic antitumor therapy and can negatively impact food intake and quality of life. This study aimed to examine the occurrence of TAs and SAs and investigate the impact of TAs on overall liking of oral nutritional supplements (ONS) with warming and cooling sensations. METHODS: Patients receiving systemic antitumor therapy completed a questionnaire on sensory alterations and evaluated overall liking of 5 prototype flavors of Nutridrink® Compact Protein (hot tropical ginger (HTG), hot mango (HM), cool red fruits (CRF), cool lemon (CL), and neutral (N)) on a 10-point scale via a sip test. Differences between patients with and without TAs were investigated using permutation analysis. RESULTS: Fifty patients with various cancer types and treatments were included. Thirty patients (60%) reported TAs and 13 (26%) experienced SAs. Three flavors were rated highly with a liking score > 6 (CRF 6.8 ± 1.7; N 6.5 ± 1.9; HTG 6.0 ± 2.0). Larger variation in ONS liking scores was observed in patients with TAs with or without SAs (4.5-6.9 and 4.6-7.2, respectively) vs. patients without TAs (5.9-6.5). TAs were associated with increased liking of CRF (Δ = + 0.9) and N (Δ = + 1.0) flavors. CONCLUSIONS: TAs and SAs are common in patients with cancer undergoing systemic antitumor therapy. Patients with TAs were more discriminant in liking of ONS flavors compared to patients without TAs, and sensory-adapted flavors appeared to be appreciated. The presence of TAs should be considered when developing or selecting ONS for patients with cancer. TRIAL REGISTRATION: Registration at ClinicalTrials.gov (NCT03525236) on 26 April 2018.


Assuntos
Neoplasias , Paladar , Humanos , Neoplasias/tratamento farmacológico , Qualidade de Vida , Autorrelato , Olfato
16.
Psychooncology ; 29(3): 539-549, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31785043

RESUMO

OBJECTIVE: Unmet health care needs require additional care resources to achieve optimal patient well-being. In this nationwide study we examined associations between a number of risk factors and unmet needs after treatment among women with breast cancer, while taking into account their health care practices. We expected that more care use would be associated with lower levels of unmet needs. METHODS: A multicenter, prospective, observational design was employed. Women with primary breast cancer completed questionnaires 6 and 15 months post-diagnosis. Medical data were retrieved from medical records. Direct and indirect associations between sociodemographic and clinical risk factors, distress, care use, and unmet needs were investigated with structural equation modeling. RESULTS: Seven hundred forty-six participants completed both questionnaires (response rate 73.7%). The care services received were not negatively associated with the reported levels of unmet needs after treatment. Comorbidity was associated with higher physical and daily living needs. Higher age was associated with higher health system-related and informational needs. Having had chemotherapy and a mastectomy were associated with higher sexuality needs and breast cancer-specific issues, respectively. A higher level of distress was associated with higher levels of unmet need in all domains. CONCLUSIONS: Clinicians may use these results to timely identify which women are at risk of developing specific unmet needs after treatment. Evidence-based, cost-effective (online) interventions that target distress, the most influential risk factor, should be further implemented and disseminated among patients and clinicians.


Assuntos
Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Adulto , Idoso , Neoplasias da Mama/terapia , Feminino , Humanos , Mastectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Avaliação das Necessidades/normas , Estudos Prospectivos , Fatores de Risco , Apoio Social , Inquéritos e Questionários
17.
Support Care Cancer ; 28(7): 3023-3032, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31511981

RESUMO

PURPOSE: We examined distress levels, problems, referral wish, and supportive health care use in a cross-sectional group of breast cancer survivors at two-time points with a 1-year time interval. Also, factors related to continuing elevated distress were explored. METHODS: Breast cancer survivors, 1-5 years after chemotherapy completion, filled in the Dutch Distress Thermometer/Problem List (DT/PL) and questions on background characteristics at study inclusion (T1). DT/PL responses and health care use were discussed during semi-structured interviews. One year later, re-assessment took place (T2). The data were analyzed by descriptive and univariate analyses. Continuing elevated distress was defined as a DT score ≥ 5 at T1 and T2. RESULTS: Seventy-three survivors completed all questionnaires (response = 84.6%). Eighteen (25%) experienced continuing elevated distress. Fatigue (T1 N = 48 (66%); T2 N = 41 (56%)) and lack of physical fitness (T1 N = 44 (60%); T2 N = 36 (49%)) were most often reported. Time since diagnosis, health care use, and practical, social, emotional and physical problems were significantly associated with continuing elevated distress. Between diagnosis and T1, N = 49(67%) used supportive healthcare services, mostly a psychologist and/or a physical/lymphedema therapist, and between T1 and T2, 39 (53%) did. At T1, 8 (11%) expressed a referral wish and at T2, 11 (16%) did. CONCLUSIONS: Screening and management of distress, problems, and referral wish are important, even years after chemotherapy completion as a substantial proportion of breast cancer survivors continue to report elevated distress and problems. Special attention should be paid to survivors reporting physical problems, especially fatigue and lack of physical fitness, since these problems are most strongly related to continuing elevated distress.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Estresse Psicológico/etiologia , Estudos Transversais , Fadiga/etiologia , Fadiga/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Cuidados Paliativos , Encaminhamento e Consulta , Fatores Sociológicos , Estresse Psicológico/diagnóstico , Estresse Psicológico/psicologia , Inquéritos e Questionários
18.
Oncologist ; 24(6): e387-e390, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30670599

RESUMO

In patients with a suspected malignancy, standard-of care management currently includes histopathologic examination and analysis of tumor-specific molecular abnormalities. Herein, we present a 77-year-old patient with an abdominal mass suspected to be a gastrointestinal stromal tumor (GIST) but without the possibility to collect a tumor biopsy. Cell-free DNA extracted from a blood sample was analyzed for the presence of mutations in GIST-specific genes using next generation sequencing. Furthermore, liquid biopsies were used to monitor the levels of mutant DNA copies during treatment with a tumor-specific mutation droplet digital PCR assay that correlated with the clinical and radiological response. Blood-based testing is a good alternative for biopsy-based testing. However, it should only be applied when biopsies are not available or possible to obtain because overall, in only 50%-85% of the cell-free plasma samples is the known tumor mutation detected.


Assuntos
DNA Tumoral Circulante/sangue , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Mesilato de Imatinib/uso terapêutico , Mutação , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Feminino , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/sangue , Tumores do Estroma Gastrointestinal/patologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Biópsia Líquida , Reação em Cadeia da Polimerase/métodos , Prognóstico
19.
Pharmacogenomics J ; 19(5): 473-479, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30713339

RESUMO

Imatinib has a mild toxicity profile, although severe adverse events may develop. In this pharmacogenetic pathway analysis the need for dose reduction and cessation of therapy was tested for an association with single nucleotide polymorphisms (SNPs) in genes related to imatinib pharmacology. Retrospective data from 315 patients with a gastrointestinal stromal tumor who received imatinib 400 mg o.d. was associated with 36 SNPs. SNPs that showed a trend in univariate testing were tested in a multivariate model with clinical factors and correction for multiple testing was performed. Dose reduction was associated with carriership of the A-allele in rs2231137 in ABCG2 (OR 7.35, p = 0.0002) and two C-alleles in rs762551 in CYP1A2 (OR 7.12, p = 0.001). Results remained significant after correction for multiple testing. Therapy cessation did not show an association with any of the tested SNPs. These results may help identifying patients at increased risk for toxicity who could benefit from intensified follow-up.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Citocromo P-450 CYP1A2/genética , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Mesilato de Imatinib/administração & dosagem , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Gastrointestinais/genética , Tumores do Estroma Gastrointestinal/genética , Humanos , Mesilato de Imatinib/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
20.
Ther Drug Monit ; 41(5): 561-567, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31568233

RESUMO

BACKGROUND: Oral anticancer drugs show a high interpatient variability in pharmacokinetics (PK), leading to large differences in drug exposure. For many of these drugs, exposure has been linked to efficacy and toxicity. Despite this knowledge, these drugs are still administered in a one-size-fits-all approach. Consequently, individual patients have a high probability to be either underdosed, which can lead to decreased antitumor efficacy, or overdosed, which could potentially result in increased toxicity. Therapeutic drug monitoring (TDM), personalized dosing based on measured drug levels, could be used to circumvent underdosing and overdosing and thereby optimize treatment outcomes. METHODS: In this prospective clinical study (www.trialregister.nl; NL6695), the feasibility, tolerability, and efficacy of TDM of oral anticancer drugs will be evaluated. In total, at least 600 patients will be included for (at least) 23 different compounds. Patients starting regular treatment with one of these compounds at the approved standard dose can be included. PK sampling will be performed at 4, 8, and 12 weeks after the start of treatment and every 12 weeks thereafter. Drug concentrations will be measured, and trough concentrations (Cmin) will be calculated. In cases where Cmin falls below the predefined target and acceptable toxicity, a PK-guided intervention will be recommended. This could include emphasizing compliance, adapting concomitant medication (due to drug-drug interactions), instructing to take the drug concomitant with food, splitting intake moments, or recommending a dose increase. DISCUSSION: Despite a strong rationale for the use of TDM for oral anticancer drugs, this is currently not yet widely adopted in routine patient care. This prospective study will be a valuable contribution to demonstrate the additional value of dose optimization on treatment outcome for these drugs.


Assuntos
Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Administração Oral , Interações Medicamentosas/fisiologia , Monitoramento de Medicamentos/métodos , Humanos , Oncologia/métodos , Estudos Prospectivos , Resultado do Tratamento
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