ABSTRACT
BACKGROUND: In recent years, there has been a change in the therapeutic landscape of desmoid-type fibromatosis (DF). Watchful waiting is now preferred over initial local treatments such as surgery and radiotherapy. Systemic treatment is considered for progressive or symptomatic disease. The aim of this study is to review real-life data on the use of sorafenib in DF. METHODS: We established a retrospective dataset of patients treated with sorafenib in our centre, Ghent University Hospital, for progressive DF. Patient demographics, disease characteristics, response to therapy using Response Evaluation Criteria in Solid Tumours 1.1 criteria and toxicity according to CTCAE v5.0 were assessed. RESULTS: Eleven patients with DF were treated with sorafenib between 2020 and 2024. Median treatment duration was 20.4 months (95% confidence interval [CI], 10.0-NR). 36.4% achieved partial response, 54.5% stable disease and 9.1% progressive disease. For three patients, the treatment is ongoing. The median time to objective response rate is 15.0 months (95% CI, 8.8-NR). The majority (81.8%) experienced grade 2 toxicity, and one third of patients grade 3 toxicity (36.4%). The most common all-grade adverse event was skin toxicity (hand-foot syndrome, pruritus and rash) (90.9%). Nine patients (81.8%) needed dose reduction with a median time to first reduction of 1.1 months (95% CI, 0.5-NR). One patient stopped treatment due to toxicity. INTERPRETATION: Real-life data on the use of sorafenib in the treatment of DF is consistent with published data in clinical trial setting. Sorafenib is an effective treatment option for progressive DF although associated with significant toxicity and the need for rapid dose reduction.
Subject(s)
Antineoplastic Agents , Fibromatosis, Aggressive , Sorafenib , Humans , Sorafenib/therapeutic use , Sorafenib/adverse effects , Female , Male , Fibromatosis, Aggressive/drug therapy , Fibromatosis, Aggressive/pathology , Middle Aged , Retrospective Studies , Adult , Aged , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Young Adult , Treatment OutcomeABSTRACT
BACKGROUND: The decreased perfusion of osteosarcoma in dynamic contrast-enhanced (DCE) MRI, reflecting a good histological response to neoadjuvant chemotherapy, has been described. PURPOSE: In this study, we aim to explore the potential of the relative wash-in rate as a prognostic factor for event-free survival (EFS). METHODS: Skeletal high-grade osteosarcoma patients, treated in two tertiary referral centers between 2005 and 2022, were retrospectively included. The relative wash-in rate (rWIR) was determined with DCE-MRI before, after, or during the second cycle of chemotherapy (pre-resection). A previously determined cut-off was used to categorize patients, where rWIR < 2.3 was considered poor and rWIR ≥ 2.3 a good radiological response. EFS was defined as the time from resection to the first event: local recurrence, new metastases, or tumor-related death. EFS was estimated using Kaplan-Meier's methodology. Multivariate Cox proportional hazard model was used to estimate the effect of histological response and rWIR on EFS, adjusted for traditional prognostic factors. RESULTS: Eighty-two patients (median age: 17 years; IQR: 14-28) were included. The median follow-up duration was 11.8 years (95% CI: 11.0-12.7). During follow-up, 33 events occurred. Poor histological response was not significantly associated with EFS (HR: 1.8; 95% CI: 0.9-3.8), whereas a poor radiological response was associated with a worse EFS (HR: 2.4; 95% CI: 1.1-5.0). In a subpopulation without initial metastases, the binary assessment of rWIR approached statistical significance (HR: 2.3; 95% CI: 1.0-5.2), whereas its continuous evaluation demonstrated a significant association between higher rWIR and improved EFS (HR: 0.7; 95% CI: 0.5-0.9), underlining the effect of response to chemotherapy. The 2- and 5-year EFS for patients with a rWIR ≥ 2.3 were 85% and 75% versus 55% and 50% for patients with a rWIR < 2.3. CONCLUSION: The predicted poor chemo response with MRI (rWIR < 2.3) is associated with shorter EFS even when adjusted for known clinical covariates and shows similar results to histological response evaluation. rWIR is a potential tool for future response-based individualized healthcare in osteosarcoma patients before surgical resection.
ABSTRACT
OBJECTIVE: To identify predictors of sexual satisfaction in patients with advanced cancer and their family caregivers. METHODS: Cross-sectional study using baseline survey data from a randomized controlled trial in six European countries. Patients with advanced cancer and their family caregiver completed measures on sexual satisfaction (one item from Functional Assessment of Cancer Therapy - General questionnaire for patients and Caregiver Quality of Life Index-Cancer scale for family caregivers) and health-related characteristics. Multivariable linear regressions were performed for all predictors (identified based on literature) with sexual satisfaction as dependent variable. RESULTS: The sample comprised 431 patient-family caregiver dyads. Patients with prostate or gynecological cancer reported lower sexual satisfaction (respectively B = -0.267 95% CI: -1.674, -0.594 and B = -0.196, 95% CI -2.103, -0.452). Higher emotional (B = 0.278, 95% CI 0.024, 0.057) physical (B = 0.305, 95% CI 0.012, 0.025) and social functioning (B = 0.151, 95% CI 0.001, 0.013), global health (B = 0.356, 95% CI 0.007, 0.013) and social wellbeing (B = 0.161, 95% CI 0.013, 0.082) among patients were associated with higher sexual satisfaction. Among family caregivers, sexual satisfaction was lower with increased age (B = -0.142, 95% CI -0.022, -0.004). Higher emotional functioning (B = 0.027, 95% CI 0.011, 0.043) and quality of life (B = 0.165, 95% CI -0.165, 0.716) were associated with higher sexual satisfaction in family caregivers. CONCLUSIONS: The results underscore that sexual wellbeing of patients and family caregivers is related to health related factors in physical, emotional, and social domains. Patients and family caregivers could benefit from a dyadic approach to address sexual wellbeing.
Subject(s)
Caregivers , Neoplasms , Quality of Life , Humans , Caregivers/psychology , Male , Female , Middle Aged , Cross-Sectional Studies , Europe , Neoplasms/psychology , Quality of Life/psychology , Aged , Adult , Surveys and Questionnaires , Personal Satisfaction , Orgasm , Sexual Behavior/psychologyABSTRACT
Despite optimal multimodal treatment including surgical resection, 50%-80% of high-grade soft tissue sarcoma (STS) patients metastasize. Here, we present a protocol for the generation and use of post-surgical minimal residual disease models to investigate metastatic relapse in STS patient-derived xenografts. We describe steps for orthotopic engraftment of high-grade STS patient-derived tumor tissue. We then detail procedures for primary tumor resection with broad, negative resection margins and follow-up until metastases using MRI. For complete details on the use and execution of this protocol, please refer to Fischer et al. (2023).1.
Subject(s)
Sarcoma , Soft Tissue Neoplasms , Humans , Neoplasm, Residual , Heterografts , Sarcoma/diagnostic imaging , Sarcoma/surgery , Sarcoma/pathology , Soft Tissue Neoplasms/diagnostic imaging , Soft Tissue Neoplasms/surgery , Soft Tissue Neoplasms/pathology , Magnetic Resonance ImagingABSTRACT
OBJECTIVE: To identify which dynamic contrast-enhanced (DCE-)MRI features best predict histological response to neoadjuvant chemotherapy in patients with an osteosarcoma. METHODS: Patients with osteosarcoma who underwent DCE-MRI before and after neoadjuvant chemotherapy prior to resection were retrospectively included at two different centers. Data from the center with the larger cohort (training cohort) was used to identify which method for region-of-interest selection (whole slab or focal area method) and which change in DCE-MRI features (time to enhancement, wash-in rate, maximum relative enhancement and area under the curve) gave the most accurate prediction of histological response. Models were created using logistic regression and cross-validated. The most accurate model was then externally validated using data from the other center (test cohort). RESULTS: Fifty-five (27 poor response) and 30 (19 poor response) patients were included in training and test cohorts, respectively. Intraclass correlation coefficient of relative DCE-MRI features ranged 0.81-0.97 with the whole slab and 0.57-0.85 with the focal area segmentation method. Poor histological response was best predicted with the whole slab segmentation method using a single feature threshold, relative wash-in rate <2.3. Mean accuracy was 0.85 (95%CI: 0.75-0.95), and area under the receiver operating characteristic curve (AUC-index) was 0.93 (95%CI: 0.86-1.00). In external validation, accuracy and AUC-index were 0.80 and 0.80. CONCLUSION: In this study, a relative wash-in rate of <2.3 determined with the whole slab segmentation method predicted histological response to neoadjuvant chemotherapy in osteosarcoma. Consistent performance was observed in an external test cohort.
Subject(s)
Bone Neoplasms , Osteosarcoma , Humans , Neoadjuvant Therapy/methods , Retrospective Studies , Treatment Outcome , Magnetic Resonance Imaging/methods , Osteosarcoma/diagnostic imaging , Osteosarcoma/drug therapy , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/drug therapyABSTRACT
OBJECTIVE: To determine the value of CT and dynamic contrast-enhanced (DCE-)MRI for monitoring denosumab therapy of giant cell tumors of bone (GCTB) by correlating it to histopathology. MATERIALS AND METHODS: Patients with GCTB under denosumab treatment and monitored with CT and (DCE-)MRI (2012-2021) were retrospectively included. Imaging and (semi-)quantitative measurements were used to assess response/relapse. Tissue samples were analyzed using computerized segmentation for vascularization and number of neoplastic and giant cells. Pearson's correlation/Spearman's rank coefficient and Kruskal-Wallis tests were used to assess correlations between histopathology and radiology. RESULTS: Six patients (28 ± 8years; five men) were evaluated. On CT, good responders showed progressive re-ossification (+7.8HU/month) and cortical remodeling (woven bone). MRI showed an SI decrease relative to muscle on T1-weighted (-0.01 A.U./month) and on fat-saturated T2-weighted sequences (-0.03 A.U./month). Time-intensity-curves evolved from a type IV with high first pass, high amplitude, and steep wash-out to a slow type II. An increase in time-to-peak (+100%) and a decrease in Ktrans (-71%) were observed. This is consistent with microscopic examination, showing a decrease of giant cells (-76%), neoplastic cells (-63%), and blood vessels (-28%). There was a strong statistical significant inverse correlation between time-to-peak and microvessel density (ρ = -0.9, p = 0.01). Significantly less neoplastic (p = 0.03) and giant cells (p = 0.04) were found with a time-intensity curve type II, compared to a type IV. Two patients showed relapse after initial good response when stopping denosumab. Inverse imaging and pathological findings were observed. CONCLUSION: CT and (DCE-)MRI show a good correlation with pathology and allow adequate evaluation of response to denosumab and detection of therapy failure.
Subject(s)
Bone Density Conservation Agents , Bone Neoplasms , Giant Cell Tumor of Bone , Radiology , Male , Humans , Denosumab/therapeutic use , Retrospective Studies , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/drug therapy , Neoplasm Recurrence, Local , Giant Cell Tumor of Bone/diagnostic imaging , Giant Cell Tumor of Bone/drug therapy , Giant Cell Tumor of Bone/pathology , RecurrenceABSTRACT
We report an exceptional case of a spindle cell mesenchymal tumor with S100 and CD34 co-reactivity, which harbored a SLMAP::RAF1 fusion. To the best of our knowledge, this is the second case of a spindle cell mesenchymal tumor with S100 and CD34 co-reactivity with this specific fusion. Remarkable is the presence of calcification and heterotopic ossification in the center of our lesion, a feature that, to our knowledge, has not been described yet in RAF1-rearranged spindle cell mesenchymal tumors.
Subject(s)
Choristoma , Ossification, Heterotopic , Sarcoma , Soft Tissue Neoplasms , Humans , Sarcoma/pathology , Ossification, Heterotopic/genetics , Soft Tissue Neoplasms/complications , Soft Tissue Neoplasms/genetics , Soft Tissue Neoplasms/pathology , Biomarkers, TumorABSTRACT
Background: eHealth programs could be a flexible and scalable resource to support and empower people with advanced cancer and their family caregivers. A face-to-face intervention that has demonstrated effectiveness is the "FOCUS" program, developed and tested in the USA. Recently the FOCUS program was translated and adapted to the European context as part of an international study in six European countries, resulting in the "FOCUS+" program. FOCUS+ served as the basis for development of the web-based iFOCUS program. Objective: We aim to (1) describe the development process of the iFOCUS program, (2) outline the challenges we encountered and how they were overcome, and (3) present findings regarding the acceptability and usability of iFOCUS. Methods: We used the four phased agile Scrum methodology to develop iFOCUS and applied set timeframes of rapid program development and evaluation (sprints). Five teams were involved in the development i.e. a core development group, a web development team, an international consortium, audio-visual experts, and potential end-users. Results: Development followed seven steps, integrated across the four phases of Scrum: (1) concept design, (2) development of mock-ups, (3) Feedback from the international consortium, (4) technical development of iFOCUS, (5) creating versions for the six participating countries, (6) preliminary testing of iFOCUS and (7) implementing the final version in a randomized controlled trial. User testing included 42 participants (twenty patient-family caregiver dyads and two bereaved family caregivers) who reviewed the iFOCUS program. Users found the iFOCUS program to be acceptable and usable. Feedback mainly focused on text size and fonts. Minor changes to the content, tailoring, and program flow were required. During development we encountered program specific and general challenges. Using the Scrum methodology facilitated iterative development to address these issues. For some challenges, such as tailoring, we had to make pragmatic choices due to time and resource limitations. Conclusions/discussion: The development of a tailored, self-managed psychoeducational eHealth program for people with advanced cancer and their family caregivers is an intense process and requires pragmatic choices. By keeping the emphasis on the target population during development, no specific remarks pertaining to advanced cancer were identified. Some challenges we encountered are common to eHealth development, others were related to program specific requirements. Using the Scrum methodology allows teams to efficiently collaborate during program development and increases the flexibility of the development process. Interpersonal contact between research staff and potential end-users is recommended during and after the development of eHealth programs.
ABSTRACT
BACKGROUND: Over the past decades, advancements in oncological treatments have led to major improvements in survival. Particularly for adolescents and young adults (AYAs), fertility is an important concern in cancer survivorship. The purpose of the review is to provide physicians with a practical overview of the current knowledge about the impact of systemic oncological treatments on the fertility of female and male AYAs. METHODS: A systematic review was performed based on relevant articles obtained from 4 databases up until 31 December 2022. RESULTS: The mechanisms of gonadotoxicity and the concurrent risk is described for the following categories: chemotherapy, targeted therapy and immunotherapy. For the category "chemotherapy", the specific effects and risks are listed for the different classes and individual chemotherapeutics. In the category "targeted therapy", a distinction was made between tyrosine kinase inhibitors (TKIs) and monoclonal antibodies. Information concerning immunotherapy is scarce. CONCLUSIONS: The effects of chemotherapy on fertility are well investigated, but even in this category, results can be conflicting. Insufficient data are available on the fertility effects of targeted therapy and immunotherapy to draw definitive conclusions. More research is needed for these therapies and their evolving role in treating cancers in AYAs. It would be useful to include fertility endpoints in clinical trials that evaluate new and existing oncological treatments.
ABSTRACT
BACKGROUND: Desmoid tumors are rare, locally aggressive, highly recurrent soft-tissue tumors without approved treatments. METHODS: We conducted a phase 3, international, double-blind, randomized, placebo-controlled trial of nirogacestat in adults with progressing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were assigned in a 1:1 ratio to receive the oral γ-secretase inhibitor nirogacestat (150 mg) or placebo twice daily. The primary end point was progression-free survival. RESULTS: From May 2019 through August 2020, a total of 70 patients were assigned to receive nirogacestat and 72 to receive placebo. Nirogacestat had a significant progression-free survival benefit over placebo (hazard ratio for disease progression or death, 0.29; 95% confidence interval, 0.15 to 0.55; P<0.001); the likelihood of being event-free at 2 years was 76% with nirogacestat and 44% with placebo. Between-group differences in progression-free survival were consistent across prespecified subgroups. The percentage of patients who had an objective response was significantly higher with nirogacestat than with placebo (41% vs. 8%; P<0.001), with a median time to response of 5.6 months and 11.1 months, respectively; the percentage of patients with a complete response was 7% and 0%, respectively. Significant between-group differences in secondary patient-reported outcomes, including pain, symptom burden, physical or role functioning, and health-related quality of life, were observed (P≤0.01). Frequent adverse events with nirogacestat included diarrhea (in 84% of the patients), nausea (in 54%), fatigue (in 51%), hypophosphatemia (in 42%), and maculopapular rash (in 32%); 95% of adverse events were of grade 1 or 2. Among women of childbearing potential receiving nirogacestat, 27 of 36 (75%) had adverse events consistent with ovarian dysfunction, which resolved in 20 women (74%). CONCLUSIONS: Nirogacestat was associated with significant benefits with respect to progression-free survival, objective response, pain, symptom burden, physical functioning, role functioning, and health-related quality of life in adults with progressing desmoid tumors. Adverse events with nirogacestat were frequent but mostly low grade. (Funded by SpringWorks Therapeutics; DeFi ClinicalTrials.gov number, NCT03785964.).
Subject(s)
Antineoplastic Agents , Fibromatosis, Aggressive , Gamma Secretase Inhibitors and Modulators , Tetrahydronaphthalenes , Adult , Female , Humans , Amyloid Precursor Protein Secretases/therapeutic use , Antineoplastic Agents/therapeutic use , Double-Blind Method , Fibromatosis, Aggressive/drug therapy , Gamma Secretase Inhibitors and Modulators/therapeutic use , Progression-Free Survival , Quality of Life , Tetrahydronaphthalenes/therapeutic use , Valine/analogs & derivativesABSTRACT
OBJECTIVE: To investigate pre-bereavement collaboration with healthcare professionals and its association with emotional well-being of family caregivers of people with serious illness post-bereavement. METHODS: Population-based cross-sectional survey of bereaved family caregivers of people with serious illness (N = 3000) who died two to six months before the sample was drawn (November 2019), identified through three sickness funds in Belgium. RESULTS: Response rate was 55%. As measured by the Positive and Negative Affect Schedule (PANAS), family caregivers scored lower on positive affect (PA) and higher on negative affect (NA) compared to a normative sample. Most family caregivers evaluated the pre-bereavement collaboration with healthcare professionals positively. Family caregivers' evaluation of collaboration with healthcare professionals pre-bereavement was positively associated with PA and negatively with NA, also when controlling for confounding effects of socio-demographic and clinical characteristics of the bereaved family caregiver and the deceased person. CONCLUSION: There is a positive association between perceived quality of collaboration at the end of life between healthcare professionals and family caregivers and post-bereavement emotional well-being of family caregivers. PRACTICE IMPLICATIONS: Our findings suggest the pertinence of attention from healthcare professionals to effective collaboration with family caregivers.
Subject(s)
Bereavement , Caregivers , Humans , Caregivers/psychology , Cross-Sectional Studies , Grief , Delivery of Health Care , Family/psychologyABSTRACT
We report an exceptional case of an undifferentiated round and spindle cell sarcoma, occurring in the periprostatic region of a 54-year-old male, with a 'high-grade endometrial stromal sarcoma-like' (HG-ESS) morphology and harboring a ZC3H7B::BCOR gene fusion identified by RNA-based next-generation sequencing. In this report, we describe the striking overlap of morphologic, immunohistochemical and molecular features of this current case and previously reported similar cases with ZC3H7B::BCOR fusion-positive HG-ESS, and discuss the differential diagnosis and possible pathogenesis of this unusual entity.
Subject(s)
Endometrial Neoplasms , Sarcoma, Endometrial Stromal , Sarcoma , Female , Male , Humans , Middle Aged , Endometrial Neoplasms/pathology , Sarcoma, Endometrial Stromal/genetics , Proto-Oncogene Proteins/genetics , Repressor Proteins/genetics , Sarcoma/diagnosis , Sarcoma/geneticsABSTRACT
OBJECTIVES: Ferric carboxymaltose (FCM) is increasingly used in the management of cancer-related anemia, yet it may cause hypophosphatemia. This retrospective study describes the incidence, evolution and risk factors of hypophosphatemia in a cohort of patients with solid tumors receiving FCM. METHODS: Serum phosphorus concentration was assessed longitudinally using a random intercepts model. The probability of developing hypophosphatemia, as graded by CTCAE version 4.0, was investigated using a multi-state model. Transition hazards were modeled non-parametrically and semi-parametrically by a Cox model. Causal marginal risk differences between baseline interventions on serum phosphorus and/or FCM dose were obtained via G-computation. RESULTS: In 174 ambulatory patients with solid tumors receiving FCM at two university hospitals between October 2020 and September 2021, the risk of developing moderate-to-severe hypophosphatemia was 36.0% (95% confidence interval (CI) 28.2-43.9%) and peaked within 16 days after first FCM administration. The average duration of moderate-to-severe hypophosphatemia was 12.4 days. After adjustment for confounders, lower baseline serum phosphorus (adjusted hazard ratio (aHR) 0.88 per 0.1 mmol/L increase, 95% CI 0.79-0.98) and higher FCM dose (first dose: aHR 1.12 per 1 mg/kg increase, 95% CI 1.01-1.25; second dose: aHR 1.06 per 1 mg/kg increase, 95% CI 1.00-1.13) significantly increased the hazard of moderate-to-severe hypophosphatemia. CONCLUSION: Approximately one out of three ambulatory patients with solid tumors may develop moderate-to-severe hypophosphatemia after FCM administration. Baseline serum phosphorus and FCM dose may be modifiable risk factors that should be considered for intervention in order to mitigate the risk of hypophosphatemia.
Subject(s)
Anemia, Iron-Deficiency , Hypophosphatemia , Neoplasms , Humans , Retrospective Studies , Incidence , Anemia, Iron-Deficiency/drug therapy , Anemia, Iron-Deficiency/epidemiology , Ferric Compounds/adverse effects , Hypophosphatemia/chemically induced , Hypophosphatemia/epidemiology , Hypophosphatemia/complications , Risk Factors , Neoplasms/complications , Neoplasms/drug therapy , Neoplasms/epidemiology , PhosphorusABSTRACT
OBJECTIVES: Family caregivers play a vital role in care for people with serious illness. Reliable population-level information on family caregiving is scarce. We describe the socio-demographic and family caregiving characteristics and experiences of family caregivers of people with serious illness in the adult population. METHOD: We performed a secondary analysis of the cross-sectional population-based 19th Social-Cultural Changes survey. A random sample of 2,581 Dutch-speaking people aged 18-95, living in Flanders or Brussels, were contacted for participation in the survey between March and July 2014 using a stratified two-step sample. Differences between groups are described using Pearson chi-square tests and analysis of variance. RESULTS: Response rate was 58.7% (1,515/2,581). Over a 12-month period, 7.6% of respondents provided family care for someone with a serious illness (n = 114). They were most often aged 55-74 (36.0%), women (57.9%), worked full-time (42.3%); 31.8% provided at least 10 h of family care each week. Family caregivers of people with serious illness, compared with family caregivers of people with other conditions, provided more medical and nursing care (33.3% vs. 22.5%, p = 0.027), and experienced a higher burden of family caregiving (p = 0.038) but a similarly high meaningfulness of family caregiving. SIGNIFICANCE OF RESULTS: A considerable part of the adult working population provides family care for someone with serious illness. While family caregiving for someone with serious illness shows similarities with family caregiving for people with other conditions in terms of caregiver characteristics and the impact of caregiving on work-life balance and the meaning derived from it, it is also associated with increased burden.
Subject(s)
Caregivers , Family Characteristics , Adult , Humans , Female , Cross-Sectional Studies , Surveys and Questionnaires , Family , Cost of IllnessABSTRACT
OBJECTIVE: A late conversation about palliative care needs can lead to suboptimal care in the final months/weeks of life. Insight into factors related to patients' communication about palliative care is needed. This study aims to identify the factors associated with starting/intending to start a conversation about palliative care with the physician. METHODS: We performed a cross-sectional interviewer-administered survey among people with incurable cancer. Purposive sampling was used, taking into account theoretically relevant heterogeneity. The questionnaire was developed based on the theory of planned behavior. Uni- and multivariable logistic regression analyses were performed. RESULTS: Out of 80 participants, ten (13%) started the palliative care conversation and 18 (23%) intended to do so. People holding a positive attitude towards starting/intending to start the conversation (odds ratio [OR] 4.74; 95% CI 2.35-9.54), perceiving more benefits of it (OR 2.60; 95% CI 1.37-4.96) and perceiving a positive attitude towards the behavior in family/friends (OR 2.07; 95% CI 1.26-3.41) and the physician (OR 2.19; 95% CI 1.39-3.45) were more likely to start/intend to start a palliative care conversation; people perceiving more disadvantages (OR 0.53; 95% CI 0.32-0.87) and barriers (OR 0.31; 95% CI 0.15-0.63) were less likely to do so. These factors explained 64% of the variance. CONCLUSIONS: Our findings show that psychological and perceived socio-environmental factors, particularly patients' attitudes, are associated with starting a conversation about palliative care. Theory-based interventions targeting these strong associations might have a high potential to empower people with cancer to take the initiative in communication about palliative care and to improve timely initiation of palliative care.
Subject(s)
Neoplasms , Palliative Care , Humans , Palliative Care/psychology , Cross-Sectional Studies , Quality of Life/psychology , Surveys and Questionnaires , Neoplasms/therapy , Neoplasms/psychology , CommunicationABSTRACT
PURPOSE: Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents. METHODS: SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of study treatment were included for safety analysis (ClinicalTrials.gov identifier: NCT02606461). RESULTS: Two hundred eighty-five patients were enrolled (selinexor, n = 188; placebo, n = 97). PFS was significantly longer with selinexor versus placebo: hazard ratio (HR) 0.70 (95% CI, 0.52 to 0.95; one-sided P = .011; medians 2.8 v 2.1 months), as was time to next treatment: HR 0.50 (95% CI, 0.37 to 0.66; one-sided P < .0001; medians 5.8 v 3.2 months). With crossover, no difference was observed in overall survival. The most common treatment-emergent adverse events of any grade versus grade 3 or 4 with selinexor were nausea (151 [80.7%] v 11 [5.9]), decreased appetite (113 [60.4%] v 14 [7.5%]), and fatigue (96 [51.3%] v 12 [6.4%]). Four (2.1%) and three (3.1%) patients died in the selinexor and placebo arms, respectively. Exploratory RNA sequencing analysis identified that the absence of CALB1 expression was associated with longer PFS with selinexor compared with placebo (median 6.9 v 2.2 months; HR, 0.19; P = .001). CONCLUSION: Patients with advanced, refractory DD-LPS showed improved PFS and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of CALB1 expression as a predictive biomarker for selinexor in DD-LPS is warranted.
Subject(s)
Hydrazines , Liposarcoma , Triazoles , Child , Double-Blind Method , Humans , Hydrazines/adverse effects , Liposarcoma/drug therapy , Liposarcoma/pathology , Triazoles/adverse effectsABSTRACT
OBJECTIVES: Facilitated advance care planning (ACP) helps family carers' to be aware of patient preferences. It can improve family carers' involvement in decision making and their overall experiences at the end of life, as well as, reduce psychological stress. We investigated the effects of the ACTION Respecting Choices (RC) ACP intervention on the family carers' involvement in decision making in the last 3 months of the patients' life and on the family carers' psychological distress after 3 months of bereavement. METHODS: Over six European countries, a sample of 162 bereaved family carers returned a bereavement questionnaire. Involvement in decision making was measured with a single item of the Views of Informal Carers-Evaluation of Services Short Form questionnaire. Psychological distress was measured with the Impact of Event Scale (IES). RESULTS: No significant effect was found on family carers involvement in decision making in the last 3 months of the patients' life (95% CI 0.449 to 4.097). However, the probability of involvement in decision making was slightly higher in the intervention arm of the study (89.6% vs 86.7%; OR=1.357). Overall, no statistical difference was found between intervention and control group regarding the IES (M=34.1 (1.7) vs 31.8 (1.5); (95% CI -2.2 to 6.8)). CONCLUSION: The ACTION RC ACP intervention showed no significant effect on family carers' involvement in decision making or on subsequent psychological distress. More research is needed about (1) how family carers can be actively involved in ACP-conversations and (2) how to prepare family carers on their role in decision making. TRIAL REGISTRATION NUMBER: International Standard Randomised Controlled Trial Number ISRCTN17231.
ABSTRACT
PURPOSE: This longitudinal survey study aimed to investigate the self-reported outcome measures of COVID-19 peritraumatic distress, depression, anxiety, stress, quality of life (QOL), and their associated factors in a cohort of cancer patients treated at a tertiary care hospital during the SARS-CoV-2 pandemic. METHODS: Surveys were administered at four time points between 1 April 2020 and 18 September 2020. The surveys included the CPDI, DASS-21, and WHOQOL-BREF questionnaires. RESULTS: Survey response rates were high (61.0% to 79.1%). Among the 355 participants, 71.3% were female, and the median age was 62.2 years (IQR, 53.9 to 69.1). The majority (78.6%) were treated with palliative intention. An important proportion of the participants reported symptoms of COVID-19 peritraumatic distress (34.2% to 39.6%), depression (27.6% to 33.5%), anxiety (24.9% to 32.7%), and stress (11.4% to 15.7%) at any time point during the study period. We did not find clinically meaningful mental health and QOL differences during the study period, with remarkably little change in between the pandemic's first and second wave. We found no consistent correlates of mental health or QOL scores, including cancer type, therapy intention, and sociodemographic information. CONCLUSION: This cohort of cancer patients showed considerable resilience against mental health and QOL deterioration during the SARS-CoV-2 pandemic.
ABSTRACT
BACKGROUND: Due to medical advances and an increasingly ageing population, the number of people living with a serious illness is rising. This has major implications for the burden on family members of assisting with care. Support of family caregivers by healthcare professionals is needed to ensure they can provide quality care for people with serious illness. AIM: To investigate how family caregivers of people with serious illness are supported by healthcare professionals in their caregiving tasks. DESIGN/PARTICIPANTS: Population-based cross-sectional survey of bereaved family caregivers of people with serious illness (N = 3000) who cared for a person who had died 2-6 months before the sample was drawn (November 2019), as identified through three sickness funds in Flanders, Belgium. The survey explored support from healthcare professionals for family caregivers 3 months prior to bereavement. RESULTS: Response rate was 55.0%. Most family caregivers received support from one or more healthcare professionals for family caregiving tasks, ranging from 71% for promoting social interaction to 95% for managing symptoms. The type of support mostly involved providing information. Use of palliative care services was the strongest predictor of such support across physical, psychosocial and practical tasks. CONCLUSION: Most family caregivers of those with serious illness get some form of support from healthcare professionals for their tasks. However, an empowering support strategy for example one aimed at increasing self-efficacy of the family caregiver is rare and end-of-life communication between healthcare professionals and family caregivers needs improvement.