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BACKGROUND: The Dutch Committee for the Evaluation of Oncological Agents (cieBOM) assesses the clinical benefit of systemic anti-cancer treatments (SACTs). For SACTs tested in non-randomized trials (NRTs), cieBOM primarily utilizes response-related thresholds as assessment criteria. As sufficiency of NRT-based evidence for benefit assessments is questionable, this study investigated whether and how NRTs can be used to assess the clinical benefit of new SACTs initially appraised by cieBOM based on randomized controlled trials (RCTs). METHODS: Using the RCTs underpinning cieBOM recommendations issued between 2015 and 2017, we searched for matching NRTs and applied the NRT-related assessment criteria by cieBOM to them. We then compared the assessment outcomes to the respective RCT-based cieBOM recommendations. Further, we investigated how the assessments would change when applying different response-related thresholds and adding a progression-free survival (PFS) threshold. RESULTS: For 13 of the 37 eligible recommendations, a matching NRT was found. Two treatments were assessed positively and six negatively; five treatments were non-assessable. Two positive recommendations matched a positive NRT-based assessment; one matching negative assessment was found, and one treatment could not be assessed based on either trial results. Adding a > 6 months PFS threshold decreased the number of non-assessable NRTs (five to two). CONCLUSIONS: Limited publications and inconsistent data reporting hampered the viability of NRTs for clinical benefit assessments of SACTs beyond the scope of rare indications. Further, response-related assessment criteria alone might not fully grasp the clinical benefit of novel SACTs. NRT-based assessments should be considered with caution due to uncertainty of the trial results.
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Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
BACKGROUND: Sunitinib is an oral anticancer drug approved for the treatment of among others gastrointestinal stromal tumor (GIST). Previous analyses demonstrated an exposure-response relationship at the standard dose, and minimum target levels of drug exposure have been defined above which better treatment outcomes are observed. Therapeutic drug monitoring (TDM) could be used as a tool to optimize the individual dose, aiming at sunitinib trough concentrations ≥37.5 ng/ml for continuous dosing. Nonetheless, data on the added value of TDM-guided dosing on clinical endpoints are currently lacking. Therefore, we evaluate the effect of TDM in patients with advanced and metastatic GIST treated with sunitinib in terms of efficacy and toxicity. PATIENTS AND METHODS: A TDM-guided cohort was compared to a non-TDM-guided cohort in terms of median progression-free survival (mPFS) and overall survival (mOS). Also, mPFS between patients with and without dose-limiting toxicities (DLTs) was compared. Patients in the prospective cohort were included in two studies on TDM-guided dosing (the DPOG-TDM study and TUNE study). The retrospective cohort consisted of patients from the Dutch GIST Registry who did not receive TDM-guided dosing. RESULTS: In total, 51 and 106 patients were included in the TDM-guided cohort and non-TDM-guided cohort, respectively. No statistical difference in mPFS was observed between these two cohorts (39.4 versus 46.9 weeks, respectively; P = 0.52). Patients who experienced sunitinib-induced DLTs had longer mPFS compared to those who did not (51.9 versus 28.9 weeks, respectively; P = 0.002). CONCLUSIONS: Our results do not support the routine use of TDM-guided dose optimization of sunitinib in patients with advanced/metastatic GIST to improve survival.
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Antineoplásicos , Monitoramento de Medicamentos , Tumores do Estroma Gastrointestinal , Sunitinibe , Humanos , Sunitinibe/administração & dosagem , Sunitinibe/uso terapêutico , Sunitinibe/farmacologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Estudos Retrospectivos , Monitoramento de Medicamentos/métodos , Adulto , Resultado do Tratamento , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/mortalidade , Relação Dose-Resposta a Droga , Idoso de 80 Anos ou mais , Estudos Prospectivos , Intervalo Livre de ProgressãoRESUMO
BACKGROUND: Patient safety is crucial for quality of care. Preventable adverse events (AEs) occur in 1 of 20 patients in the hospital, but it is unknown whether this is different for patients with a condition relevant for palliative care. The majority of the limited available research on this topic is only focused on patients already receiving palliative care, and do not make comparisons with other patients at the end-of-life. We identified and compared the prevalence, preventability, nature and causes of AEs in patients with and without a condition relevant for palliative care. METHODS: A nationwide retrospective record review study was performed in 20 Dutch hospitals. A total of 2,998 records of patients who died in hospital in 2019 was included. Records were reviewed for AEs. We identified two subgroups: patients with (n = 2,370) or without (n = 248) a condition relevant for palliative care through the selection method of Etkind (2017). Descriptive analyses were performed to calculate prevalence, nature, causes and prevention strategies. T-tests were performed to calculate differences between subgroups. RESULTS: We found no significant differences between subgroups regarding AE prevalence, this was 15.3% in patients with a condition relevant for palliative care, versus 12.0% in patients without a condition relevant for palliative care (p = 0.148). Potentially preventable AE prevalence was 4.3% versus 4.4% (p = 0.975). Potentially preventable death prevalence in both groups was 3.2% (p = 0.938). There were differences in the nature of AEs: in patients with a condition relevant for palliative care this was mostly related to medication (33.1%), and in patients without a condition relevant for palliative care to surgery (50.8%). In both subgroups in the majority of AEs a patient related cause was identified. For the potentially preventable AEs in both subgroups the two most important prevention strategies as suggested by the medical reviewers were reflection and evaluation and quality assurance. DISCUSSION: Patient safety risks appeared to be equally prevalent in both subgroups. The nature of AEs does differ between subgroups: medication- versus surgery-related, indicating that tailored safety measures are needed. Recommendations for practice are to focus on reflecting on AEs, complemented with case evaluations.
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Cuidados Paliativos , Humanos , Países Baixos/epidemiologia , Estudos Retrospectivos , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Cuidados Paliativos/estatística & dados numéricos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Assistência Terminal/métodos , Assistência Terminal/normas , Assistência Terminal/estatística & dados numéricos , Adulto , Erros Médicos/estatística & dados numéricos , Segurança do Paciente/normas , Segurança do Paciente/estatística & dados numéricosRESUMO
AIM: Oxycodone is known to have numerous drug-drug interactions (DDIs) that can potentially decrease efficacy or lead to adverse drug reactions (ADRs). However, there is limited research on the frequency of DDIs associated with oxycodone, which is important in optimising pharmacovigilance and the need for additional research on certain DDIs. In this study, the frequency of pharmacologically and clinically relevant DDI perpetrators was studied in patients with cancer. METHODS: This was a cross-sectional study using hospital pharmacy records of patients with cancer who were prescribed oxycodone between September 2021 and September 2022. Medication records of patients prescribed oxycodone during a period of ≥ 5 consecutive days (= oxycodone treatment episodes) were reviewed to identify the concomitant use of pharmacologically relevant perpetrators, based on reference sources (Lexicomp®, Micromedex®, the Dutch Kennisbank and the Dutch Commentaren Medicatiebewaking). The clinical relevance was examined by a clinical pharmacologist and a medical oncologist. Additionally, the frequency of double interactions-concomitant oxycodone use with two CYP3A4 and / or CYP2D6 perpetrators-was studied. RESULTS: Overall, 254 oxycodone treatment episodes were included, of which 227 (89.4%) were found to contain at least one pharmacologically relevant DDI perpetrator. Of these, 210 (82.7%) were considered to be clinically relevant. A total of 80 different pharmacologically relevant perpetrators were identified, with 65 (81.3%) being considered clinically relevant. Double interactions were observed in 21 (8.3%) oxycodone treatment episodes. CONCLUSION: A high frequency of pharmacologically and clinically relevant perpetrators of oxycodone was observed in our cohort. Moreover, a high number of double interactions involving oxycodone was registered. More intense monitoring of DDIs may be needed to improve medication safety of patients with cancer taking oxycodone.
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Neoplasias , Oxicodona , Humanos , Oxicodona/efeitos adversos , Estudos Transversais , Relevância Clínica , Interações Medicamentosas , Neoplasias/tratamento farmacológicoRESUMO
Novel systemic therapies for advanced melanoma improve survival, but carry potential serious side effects and high costs. This study aimed to assess the timing and use of systemic therapies in the months before death. Patients diagnosed with advanced melanoma (July 2017-June 2020) who died before July 2020 were selected from the Netherlands Cancer Registry. We evaluated the timing of systemic therapies within 30 days and 3 months before death, and studied patient and tumor characteristics associated with systemic therapy use between diagnosis and death. Out of 1097 patients 68% received systemic therapy. Almost 25% and 10% started a new therapy within 90 days and within 30 days before death, respectively. Female sex, elevated LDH, BRAF mutation, poor ECOG performance status (≥3), and high comorbidity index reduced the odds of receiving immune therapy. Poor performance status and high comorbidity decreased the odds for both therapies. A considerable number of patients started systemic therapy shortly before death, emphasizing the importance of considering potential benefits and drawbacks through shared decision-making.
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Melanoma , Humanos , Feminino , Melanoma/tratamento farmacológico , Melanoma/genética , Estudos Retrospectivos , Imunoterapia , Morte , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
BACKGROUND: Quality of care at the end of life in hospitals is often perceived to be lower compared to the care that is provided to people who die in their own home. Documenting and measuring indicators of common end-of-life symptoms could help improve end-of-life care in hospitals. This study provided insight into quality indicators for the end-of-life care of patients who died in a Dutch hospital, and assessed differences between deceased patients who were admitted for palliative/terminal care versus patients admitted for other reasons. METHODS: In a retrospective record review study, trained nurses reviewed electronic health records (EHRs) of patients who died in 2019 (n = 2998), in a stratified sample of 20 Dutch hospitals. The nurses registered whether data was found in de EHRs about quality indicators for end-of-life care. This concerned: symptoms (pain, shortness of breath, anxiety, depressive symptoms), spiritual and psychological support and advance care planning. Multilevel regression analyses were performed to assess differences between patients who had been admitted for palliative/terminal care and patients admitted for other reasons. RESULTS: Common end-of-life symptoms were rarely measured using a standardized method (e.g. Numeric Rating Scale, Visual Analogue Scale or Utrecht Symptom Diary). The symptom burden of pain was measured using a standardized method more often (63.3%) than the symptom burden of shortness of breath (2.2%), anxiety (0.5%) and depressive symptoms (0.3%). Similarly, little information was documented in the EHRs regarding wish to involve a spiritual counsellor, psychologist or social worker. Life expectancy was documented in 66%. The preferred place of death was documented less often (20%). The documentation of some quality indicators differed between patients who were admitted for palliative/terminal care compared to other patients. CONCLUSION: Except for the burden of pain, symptoms are rarely measured with standardized methods in patients who died in Dutch Hospitals. This study underlines the importance of documenting information about symptom burden and aspects related to advance care planning, and spiritual and psychological support to improve the quality of end-of-life care for patients in hospitals. Furthermore, uniformity in measuring methods improves the possibility to compare results between patient groups and settings.
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Indicadores de Qualidade em Assistência à Saúde , Assistência Terminal , Humanos , Estudos Retrospectivos , Assistência Terminal/métodos , Cuidados Paliativos/métodos , Dor , Hospitais , Morte , Documentação , DispneiaRESUMO
BACKGROUND AND OBJECTIVE: Up to 90% of patients with castration-resistant prostate cancer (CRPC) will develop symptomatic bone metastases requiring pain medication, with opioids being the mainstay of therapy in treating moderate and severe pain. Enzalutamide is an androgen receptor antagonist for the treatment of CRPC and a strong inducer of cytochrome P450 (CYP)3A4. Hereby, enzalutamide potentially reduces the exposure of oxycodone, an opioid metabolized by CYP3A4 and CYP2D6. Our objective was to evaluate the potential drug-drug interaction of enzalutamide and oxycodone. METHODS: A prospective, nonrandomized, open-label, two-arm parallel study was performed. All patients received a single dose of 15 mg normal-release oxycodone. Patients in the enzalutamide arm (ENZ-arm) received enzalutamide 160 mg once daily. Plasma concentrations of oxycodone and its metabolites were quantified using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. RESULTS: Twenty-six patients (13 ENZ-arm; 13 control arm) were enrolled in the study. Enzalutamide decreased the mean AUC0-8 h and Cmax of oxycodone with, respectively, 44.7% (p < 0.001) and 35.5% (p = 0.004) compared with the control arm. The AUC0-8 h and Cmax of the active metabolite oxymorphone were 74.2% (p < 0.001) and 56.0% (p = 0.001) lower in the ENZ-arm compared with the control arm. In contrast, AUC0-8 h and Cmax of the inactive metabolites noroxycodone and noroxymorphone were significantly increased by enzalutamide. CONCLUSION: Co-administration of enzalutamide significantly reduced exposure to oxycodone and its active metabolite oxymorphone in men with prostate cancer. This should be taken into account when prescribing enzalutamide combined with oxycodone.
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Oxicodona , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Oximorfona/metabolismo , Cromatografia Líquida/métodos , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Espectrometria de Massas em Tandem/métodos , Analgésicos Opioides , DorRESUMO
BACKGROUND: Sex differences in cancer have gained attention in recent years. The role of sex as a prognostic factor in gastrointestinal stromal tumours (GIST) has not been well established. The aim of this research was to elucidate potential sex differences in GIST patients and the influence of sex on disease-specific survival (DSS). METHODS: A review of the literature was carried out to obtain an overview of all literature with sex as a covariate on GIST survival analyses. Furthermore, in the Dutch GIST Registry, GIST characteristics between males and females were compared and the influence of sex on DSS was analysed. RESULTS: A total of 118 articles from the review of the literature met our selection criteria; 58% of the articles found no sex difference in survival and 42% did find a sex difference. All differences favoured female patients, although there was substantial overlap of individual patients in the various reported groups. The Dutch GIST Registry cohort consisted of 1425 patients (46% female). Compared with female patients, male patients had larger tumours (mean 9.0 cm versus 7.9 cm) and higher mitotic rates (34.4% versus 28.0% >5 mitoses/5 mm2). GIST in males was more often metastasized at diagnosis (21.3% versus 13.7%) and incurable (38.5% versus 31.0%). Male patients less often received surgery of the primary tumour (71.7% versus 78.9%), but did experience more tumour ruptures (18.2% versus 13.3%). Male patients had a worse DSS than females. This was not statistically significant when corrected for differences in GIST characteristics. CONCLUSIONS: In case of sex differences in GIST in the literature, male patients have a worse outcome. In our Dutch GIST cohort a similar finding was made, but sex was shown not to be an independent factor. Male patients more often had aggressive GISTs, with larger tumours, higher mitotic rates, more tumour ruptures, and metastases, which could explain the sex differences in DSS.
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Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Humanos , Masculino , Feminino , Análise de SobrevidaRESUMO
BACKGROUND: Patients with advanced heart failure may benefit from palliative care, including advance care planning (ACP). ACP, which can include referral back to the general practitioner (GP), may prevent unbeneficial hospital admissions and interventional/surgical procedures that are not in accordance with the patient's personal goals of care. AIM: To implement ACP in patients with advanced heart failure and explore the effect of ACP on healthcare utilisation as well as the satisfaction of patients and cardiologists. METHODS: In this pilot study, we enrolled 30 patients with New York Heart Association class III/IV heart failure who had had at least one unplanned hospital admission in the previous year because of heart failure. A structured ACP conversation was held and documented by the treating physician. Primary outcome was the number of visits to the emergency department and/or admissions within 3 months after the ACP conversation. Secondary endpoints were the satisfaction of patients and cardiologists as established by using a five-point Likert scale. RESULTS: Median age of the patients was 81 years (range 33-94). Twenty-seven ACP documents could be analysed (90%). Twenty-one patients (78%) did not want to be readmitted to the hospital and subsequently none of them were readmitted during follow-up. Twenty-two patients (81%) discontinued all hospital care. All patients who died during follow-up (nâ¯= 12, 40%) died at home. Most patients and cardiologists indicated that they would recommend the intervention to others (80% and 92% respectively). CONCLUSION: ACP, and subsequent out-of-hospital care by the GP, was shown to be applicable in the present study of patients with advanced heart failure and evident palliative care needs. Patients and cardiologists were satisfied with this intervention.
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BACKGROUND: This study aimed to provide insights into the real-world use of palbociclib, dose reductions, and drug effectiveness in (older) patients with advanced breast cancer (BC). PATIENTS AND METHODS: Patients with advanced BC treated with palbociclib from 2017 to 2020 were included. The Kaplan-Meier method was used to calculate time to next treatment (TTNT) and overall survival (OS) for patients with or without dose reductions. These clinical outcomes were also compared in subgroup analyses for older patients (≥70 years) and younger patients (<70 years) and for patients discontinuing palbociclib early (<4 administrations). RESULTS: A total of 598 patients with advanced BC were included, with a median age of 64 years. Palbociclib dose reductions occurred in 33% of all patients. Early discontinuation of palbociclib without dose reductions occurred in 23% of the patients. Patients who required a palbociclib dose reduction were older (median age 67 years vs. 63 years). Patients with dose reductions had a significantly higher TTNT of 16.9 vs. 11.4 months (p < 0.001) and median OS of 29.7 vs. 21.9 months (p = 0.003) compared to patients without dose reductions. The TTNT in older patients was significantly longer (16.9 vs. 11.6 months, p = 0.013) than younger patients, but OS was similar (20.7 vs. 26.7 months, p = 0.051). CONCLUSION: Palbociclib dose reductions occurred in real-world practice similarly to the PALOMA-3 trial. Patients with dose reductions had no poorer outcomes compared to patients not requiring a dose reduction. Older patients treated with palbociclib had more frequent dose reductions, but this did not appear to affect OS.
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Neoplasias da Mama , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Redução da Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Piperazinas , Piridinas , Receptor ErbB-2RESUMO
BACKGROUND: Licensed systemic treatment options for platinum-sensitive recurrent ovarian cancer are platinum-based chemotherapy and maintenance treatment with bevacizumab and poly (ADP-ribose) polymerase inhibitors. For platinum-resistant disease, several non-platinum options are available. We aimed to assess the clinical benefit of these treatments according to the European Society of Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS). MATERIALS AND METHODS: A PubMed search was carried out including all studies evaluating systemic treatment of recurrent epithelial ovarian cancer, from 1990 onwards. Randomised trials with an adequate comparator and design showing a statistically significant benefit of the study arm were independently scored by two blinded observers using the ESMO-MCBS. RESULTS: A total of 1127 papers were identified, out of which 61 reported results of randomised trials of sufficient quality. Nineteen trials showed statistically significant results and the studied treatments were graded according to ESMO-MCBS. Only three treatments showed substantial benefit (score of 4 on a scale of 1-5) according to the ESMO-MCBS: platinum-based chemotherapy with paclitaxel in the platinum-sensitive setting and the addition of bevacizumab to chemotherapy in the platinum-resistant setting. The WEE1 inhibitor adavosertib (not licensed) also scores a 4, based on a recent small phase II study. Assessment of quality-of-life data and toxicity using the ESMO-MCBS showed to be complex, which should be taken into account in using this score for clinical decision making. CONCLUSION: Only a few licensed systemic therapies for recurrent ovarian cancer show substantial clinical benefit based on ESMO-MCBS scores. Trials demonstrating overall survival benefit are sparse.
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Recidiva Local de Neoplasia , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/tratamento farmacológico , Feminino , Humanos , Oncologia , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Qualidade de VidaRESUMO
Cancer therapies often cause changes in taste and smell. In this article, three patients treated with immunotherapy, chemotherapy and targeted therapy who experience changes in taste or smell are presented. These patients report lower quality of life and altered eating habits due to these changes. The prevalence and type of taste and smell changes is diverse among different cancer treatments and individual patients. In clinical practice, diagnosis is supported by questionnaires, taste strips or smell sticks. It is important to acknowledge the changes in taste and smell and inform the patient about these changes. More tools become available to provide patients with personalized advise to adjust their meals to their new sense of taste and smell at home. Furthermore, hospital cooks are implementing new strategies to adjust meals to taste and smell alterations and individual preferences. Smell training is an option for patients with severe smell disorders.
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Neoplasias , Transtornos do Olfato , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Transtornos do Olfato/etiologia , Transtornos do Olfato/terapia , Qualidade de Vida , Olfato , Paladar , Distúrbios do Paladar/etiologiaRESUMO
PURPOSE: To investigate the treatment goals of older patients with non-curable cancer, whether those goals changed over time, and if so, what triggered those changes. METHODS: We performed a descriptive and qualitative analysis using the Outcome Prioritization Tool (OPT) to assess patient goals across four conversations with general practitioners (GPs) over 6 months. Text entries from electronic patient records (hospital and general practice) were then analyzed qualitatively for this period. RESULTS: Of the 29 included patients, 10 (34%) rated extending life and 9 (31%) rated maintaining independence as their most important goals. Patients in the last year before death (late phase) prioritized extending life less often (3 patients; 21%) than those in the early phase (7 patients; 47%). Goals changed for 16 patients during follow-up (12 in the late phase). Qualitative analysis revealed three themes that explained the baseline OPT scores (prioritizing a specific goal, rating a goal as unimportant, and treatment choices related to goals). Another three themes related to changes in OPT scores (symptoms, disease course, and life events) and stability of OPT scores (stable situation, disease-unrelated motivation, and stability despite symptoms). CONCLUSION: Patients most often prioritized extending life as the most important goal. However, priorities differed in the late phase of the disease, leading to changed goals. Triggers for change related to both the disease (e.g., symptoms and course) and to other life events. We therefore recommend that goals should be discussed repeatedly, especially near the end of life. TRIAL REGISTRATION: OPTion study: NTR5419.
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Neoplasias/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Objetivos , Humanos , Masculino , Fatores de TempoRESUMO
In this questionnaire study, the attitude of dentists and students regarding the provision of oral care to palliative patients was investigated. The extent to which they would like to be involved in the care for this patient group was also investigated. The results showed that both research groups had relatively little affinity with palliative patients. In general, however, they do consider oral care to be important for this group and believe a dentist can play a role in the quality of life. About one third of both research groups, nevertheless, preferred not to be involved in the provision of oral care often. Besides, when it comes to providing oral care in nursing homes or at patients' homes, approximately one third of the respondents were not very willing or not willing at all to make house calls. Dentists and students are aware of the importance of oral care in the palliative stage of life, but they do not (yet) want to be responsible for the oral care themselves.
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Casas de Saúde , Qualidade de Vida , Odontólogos , Humanos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Standard treatment for colorectal peritoneal carcinomatosis typically involves cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and if possible, postoperative adjuvant chemotherapy. However, a substantial percentage of patients never receive adjuvant chemotherapy because of postoperative complications. Neoadjuvant chemotherapy could be beneficial in this setting, so we assessed its feasibility and safety when used before cytoreductive surgery and HIPEC. METHODS: In this non-randomized, single-center, observational feasibility study, patients were scheduled to receive six cycles of capecitabine and oxaliplatin before cytoreductive surgery and HIPEC. Computed tomography was performed after the third and sixth chemotherapy cycles to evaluate tumor response, and patients underwent cytoreductive surgery and HIPEC if there were no pulmonary and/or hepatic metastases. Postoperative complications, graded according to the Clavien-Dindo classification, were compared with those of a historic control group that received postoperative adjuvant chemotherapy. RESULTS: Of the 14 patients included in the study, 4 and 3 had to terminate neoadjuvant chemotherapy early because of toxicity and tumor progression, respectively. Cytoreductive surgery and HIPEC were performed in eight patients, and the timing and severity of complications were comparable to those of patients in the historic control group treated without neoadjuvant chemotherapy. CONCLUSION: Patients with peritoneal metastases due to colorectal carcinoma can be treated safely with neoadjuvant chemotherapy before definitive therapy with cytoreductive surgery and HIPEC. TRIAL REGISTRATION NUMBER: NTR 3905, registered on 20th march, 2013, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3905.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia do Câncer por Perfusão Regional , Neoplasias Colorretais/terapia , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Terapia Neoadjuvante , Neoplasias Peritoneais/terapia , Adulto , Idoso , Quimioterapia Adjuvante , Neoplasias Colorretais/patologia , Terapia Combinada , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/patologia , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: TKIs are a long-term treatment for GIST, and may have an impact on caregivers. MATERIAL AND METHODS: For this cross-sectional study, patients and caregivers were both included when patients had been treated with TKIs for at least six months. Caregivers completed questionnaires including demographics, distress (Hospital Anxiety and Depression scale), burden (Self-Perceived Pressure from Informal Care) general health (RAND-36), comorbidity (Self-administered Comorbidity Questionnaire), social support (Social Support List - Discrepancies) and marital satisfaction (Maudsley Marital Questionnaire). Patients completed similar questionnaires, without 'burden'. We conducted analyses to explore differences between caregivers with low/moderate versus high levels of burden and low versus high levels of distress. RESULTS: Sixty-one out of seventy-one eligible couples (84%) were included in the analysis. The median age of the caregivers was 60 years; 66% were female and 78% were the patients' spouse. The median age of the patients was 66 years; 43% were female. Caregivers experienced high levels of burden and distress in 10% and 23%, respectively. Caregivers with high levels of burden perceived significantly lower mental health, less vitality, lower general health and high levels of distress. Significantly higher levels of burden were found in non-spouses, caregivers of patients with more treatment-related side-effects, caregivers who spent more hours caring, and those caring for more than one person. For distress, caregivers with high levels of distress perceived significantly more burden, lower social functioning, more role physical and emotional problems, lower mental health, less vitality and lower general health. Furthermore, high levels of distress were found in caregivers of more dependent patients and those caring for more than one person. CONCLUSIONS: Caregivers of the patients with GIST treated with TKI are managing well. There is a small, vulnerable group of caregivers with high levels of burden and/or distress, show more health-related problems, both physical and mental, and require adequate support.
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Cuidadores/psicologia , Efeitos Psicossociais da Doença , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Estresse Psicológico/epidemiologia , Idoso , Esgotamento Psicológico/epidemiologia , Cuidadores/estatística & dados numéricos , Estudos Transversais , Feminino , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/psicologia , Tumores do Estroma Gastrointestinal/epidemiologia , Tumores do Estroma Gastrointestinal/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Tirosina Quinases/antagonistas & inibidores , Qualidade de Vida , Apoio Social , Estresse Psicológico/etiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: A cohort of 201 patients with small bowel gastrointestinal stromal tumors (GIST) treated between January 1st, 2009 and December 31st, 2016 in five GIST expertise centers in the Netherlands was analyzed. Goal of this study was to describe the clinical, surgical and pathological characteristics of this rare subpopulation of GIST patients, registered in the Dutch GIST registry. METHODS: Clinical outcomes and risk factors of patients with small bowel GIST who underwent surgery or treated with systemic therapy were analyzed. A classification was made based on disease status at diagnosis (localized vs. metastasized). RESULTS: 201 patients with small bowel GIST were registered of which 138 patients (69%) were diagnosed with localized disease and 63 patients (31%) with metastatic disease. Approximately 19% of the patients had emergency surgery, and in 22% GIST was an accidental finding. In patients with high risk localized disease, recurrence occurred less often in patients who received adjuvant treatment (4/32) compared to patients who did not (20/31, pâ¯<â¯0.01). Disease progression during palliative imatinib treatment occurred in 23 patients (28%) after a median of 20.7 (range 1.8-47.1) months. Ongoing response was established in 52/82 patients on first line palliative treatment with imatinib after a median treatment time of 30.6 (range 2.5-155.3) months. CONCLUSION: Patients with small-bowel GIST more frequently present with metastatic disease when compared to patients with gastric GIST in literature. We advocate for Prospective registration of these patients and investigate the use of surgery in patients with limited metastatic disease.
Assuntos
Antineoplásicos/uso terapêutico , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Gastrointestinais/terapia , Tumores do Estroma Gastrointestinal/terapia , Estadiamento de Neoplasias , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/epidemiologia , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Países Baixos/epidemiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida/tendências , Adulto JovemRESUMO
BACKGROUND: The magnitude of clinical benefit scale (MCBS) was introduced by the European Society of Medical Oncology (ESMO) to quantify the clinical benefit of therapeutic regimens and to prioritise therapies. It distinguishes curative from palliative treatments and ranks their benefit based on overall survival (OS), progression free survival (PFS), quality of life (QoL) and toxicity. Objective of this study on the first line treatment of ovarian cancer was to evaluate the evidence for the current standard of care using the ESMO-MCBSv1.1 with an emphasis on controversial therapeutic options: intraperitoneal chemotherapy, dose-dense paclitaxel and bevacizumab. METHODS: Phase III trials, published since 1992, investigating first line systemic treatment of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IIB-IV epithelial ovarian cancer were included. Since most studies included patients with FIGO stage IV disease or incomplete debulking, all treatments were judged to be palliative. Treatments were graded 5 to 1 on the ESMO-MCBSv1.1, where grades 5 and 4 represent a high level of clinical benefit. RESULTS: 55 studies met the inclusion criteria. ESMO-MCBS scores were calculated for eleven studies that showed a statistically significant benefit of the experimental treatment. Intraperitoneal (ip) cisplatin scored a 4 and 3, but two other studies were negative and therefore not scored on the ESMO-MCBS. Dose-dense paclitaxel showed substantial clinical benefit in one study (score 4), but three studies were negative. Addition of bevacizumab also scored a 4 in one study subgroup including high-risk patients but a 2 in another trial with a larger study population. CONCLUSION: Based on ESMO-MCBS scores, dose-dense paclitaxel and intraperitoneal chemotherapy cannot be recommended as standard treatment. Bevacizumab should be considered only in the high-risk population. The ESMO-MCBSv1.1. helps to summarise reported studies on controversial treatment regimens, and identifies their weaknesses.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Guias de Prática Clínica como Assunto/normas , Padrão de Cuidado , Feminino , Humanos , Qualidade de VidaRESUMO
PURPOSE: Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown. METHODS: In this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis. RESULTS: Of the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0-1.00) and 85.9% (75.4-92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20-2.92) or receiving a written TLD (HR 2.32, CI 1.11-4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former. CONCLUSION: Enhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life.