Cancer patients' trust as a motivator to seek a second opinion and its effects on trust

OBJECTIVE: Cancer patients may seek a second opinion (SO) driven by reduced trust in their own providers. Their trust may be diminished or reinforced through the SO. This study aimed to assess (1) what proportion of patients seek SOs motivated by lacking trust and how trust changes over time; (2) whether patients' trust differs by the outcome of the SO (i.e. similar/different opinion); and (3) how communication during the SO affects trust. DESIGN: A longitudinal mixed methods study including self-report assessments before (T0), immediately following (T1), and two months after the SO (T2). SO consultations (N = 62) were audio recorded, and patient-oncologist communication about the referring oncologist was coded. MAIN OUTCOME MEASURES: Patient-reported motives and their trust in referring oncologists. RESULTS: Reduced trust motivated 21% of patients to seek a SO. Most patients criticised their referring oncologist. Consulting oncologists generally defended their colleagues, but such affirmation was unrelated to patients' subsequent trust. Over time, trust did not change substantially. Yet, it was restored in patients motivated by impaired trust, and remained low for patients receiving a different medical outcome. CONCLUSION: Patients need support to more constructively discuss their treatment relationship. Oncologists need support in providing independent SOs without harming trust relations

Whole genome sequencing in (recurrent) glioblastoma: challenges related to informed consent procedures and data sharing

Increased use of whole genome sequencing (WGS) in neuro-oncology for diagnostics and research purposes necessitates a renewed conversation about informed consent procedures and governance structures for sharing personal health data. There is currently no consensus on how to obtain informed consent for WGS in this population. In this narrative review, we analyze the formats and contents of frameworks suggested in literature for WGS in oncology and assess their benefits and limitations. We discuss applicability, specific challenges, and legal context for patients with (recurrent) glioblastoma. This population is characterized by the rarity of the disease, extremely limited prognosis, and the correlation of the stage of the disease with cognitive abilities. Since this has implications for the informed consent procedure for WGS, we suggest that the content of informed consent should be tailor-made for (recurrent) glioblastoma patients

Perfusion imaging with arterial spin labeling (ASL)-MRI predicts malignant progression in low‑grade (WHO grade II) gliomas

PURPOSE: Predicting malignant progression of grade II gliomas would allow for earlier initiation of treatment. The hypothesis for this single-centre, case-control study was that the perfusion signal on ASL-MRI predicts such malignant progression in the following 12 months. METHODS: Consecutive patients with the following criteria were included: ≥ 18 years, grade II glioma (biopsied or resected) and an ASL-MRI 6-12 months prior to malignant progression (cases) or stable disease (controls). Malignant progression was defined either radiologically (new T1w-contrast enhancement) or histologically (neurosurgical tissue sampling). Three controls were matched with each case. Some patients served as their own control by using earlier imaging. The ASL-MRIs were reviewed by two neuroradiologists and classified as positive (hyper-intense or iso-intense compared to cortical grey matter) or negative (hypo-intense). In patients with epilepsy, a neurologist reviewed clinicoradiological data to exclude peri-ictal pseudoprogression. The statistical analysis included diagnostic test properties, a Cohen's Kappa interrater reliability coefficient and stratification for previous radiotherapy. RESULTS: Eleven cases (median age = 48, IQR = 43-50 years) and 33 controls (43, 27-50 years) were included. Malignant progression appeared at 37 months (median, IQR = 17-44) after first surgery. Thirty ASL-MRIs were assessed as negative and 14 as positive. None of the MRIs showed signs of peri-ictal pseudoprogression. ASL significantly predicted subsequent malignant progression (sensitivity = 73%; specificity = 82%; OR = 12; 95%-CI = 2.4-59.1; p = 0.002). The interrater reliability coefficient was 0.65. In stratified analysis, ASL-MRI predicted malignant progression both in patients with previous radiotherapy and in those without (Mantel-Haenszel test, p = 0.003). CONCLUSION: Perfusion imaging with ASL-MRI can predict malignant progression within 12 months in patients with grade II glioma

Venous thromboembolism and intracranial hemorrhage after craniotomy for primary malignant brain tumors: a National Surgical Quality Improvement Program analysis

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), frequently complicates the postoperative course of primary malignant brain tumor patients. Thromboprophylactic anticoagulation is commonly used to prevent VTE at the risk of intracranial hemorrhage (ICH). We extracted all patients who underwent craniotomy for a primary malignant brain tumor from the National Surgical Quality Improvement Program (NSQIP) registry (2005–2015) to perform a time-to-event analysis and identify relevant predictors of DVT, PE, and ICH within 30 days after surgery. Among the 7376 identified patients, the complication rates were 2.6, 1.5, and 1.3% for DVT, PE, and ICH, respectively. VTE was the second-most common major complication and third-most common reason for readmission. ICH was the most common reason for reoperation. The increased risk of VTE extends beyond the period of hospitalization, especially for PE, whereas ICH occurred predominantly within the first days after surgery. Older age and higher BMI were overall predictors of VTE. Dependent functional status and longer operative times were predictive for VTE during hospitalization, but not for post-discharge events. Admission two or more days before surgery was predictive for DVT, but not for PE. Preoperative steroid usage and male gender were predictive for post-discharge DVT and PE, respectively. ICH was associated with various comorbidities and longer operative times. This multicenter study demonstrates distinct critical time periods for the development of thrombotic and hemorrhagic events after craniotomy. Furthermore, the VTE risk profile depends on the type of VTE (DVT vs. PE) and clinical setting (hospitalized vs. post-discharge patients)

Focused Ultrasound-Enhanced Liquid Biopsy: A Promising Diagnostic Tool for Brain Tumor Patients

The performance of minimally invasive molecular diagnostic tools in brain tumors, such as liquid biopsy, has so far been limited by the blood-brain barrier (BBB). The BBB hinders the release of brain tumor biomarkers into the bloodstream. The use of focused ultrasound in conjunction with microbubbles has been shown to temporarily open the BBB (FUS-BBBO). This may enhance blood-based tumor biomarker levels. This systematic review provides an overview of the data regarding FUS-BBBO-enhanced liquid biopsy for primary brain tumors. A systematic search was conducted in PubMed and Embase databases with key terms "brain tumors", "liquid biopsy", "FUS" and their synonyms, in accordance with PRISMA statement guidelines. Five preclinical and two clinical studies were included. Preclinical studies utilized mouse, rat and porcine glioma models. Biomarker levels were found to be higher in sonicated groups compared to control groups. Both stable and inertial microbubble cavitation increased biomarker levels, whereas only inertial cavitation induced microhemorrhages. In clinical studies involving 14 patients with high-grade brain tumors, biomarker levels were increased after FUS-BBBO with stable cavitation. In conclusion, FUS-BBBO-enhanced liquid biopsy using stable cavitation shows diagnostic potential for primary brain tumors. Further research is imperative before integrating FUS-BBBO for liquid biopsy enhancement into clinical practice

Comparison of 2-Hydroxyglutarate Detection With sLASER and MEGA-sLASER at 7T

The onco-metabolite 2-hydroxyglutarate (2HG), a biomarker of IDH-mutant gliomas, can be detected with 1H MR spectroscopy (1H-MRS). Recent studies showed measurements of 2HG at 7T with substantial gain in signal to noise ratio (SNR) and spectral resolution, offering higher specificity and sensitivity for 2HG detection. In this study, we assessed the sensitivity of semi-localized by adiabatic selective refocusing (sLASER) and J-difference MEsher-GArwood-semi-LASER (MEGA-sLASER) for 2HG detection at 7T. We performed spectral editing at long TE using a TE-optimized sLASER sequence (110 ms) and J-difference spectroscopy using MEGA-sLASER (TE = 74ms) in phantoms with different 2HG concentrations to assess the sensitivity of 2HG detection. The robustness of the methods against B0 inhomogeneity was investigated. Moreover, the performance of these two techniques was evaluated in four patients with IDH1-mutated glioma. In contrary to MEGA-sLASER, sLASER was able to detect 2HG concentration as low as 0.5 mM. In case of a composite phantom containing 2HG with overlapping metabolites, MEGA-sLASER provided a clean 2HG signal with higher fitting reliability (lower %CRLB). The results demonstrate that sLASER is more robust against field inhomogeneities and experimental or motion-related artifacts which promotes to adopt sLASER in clinical implementations

Conventional MRI Criteria to Differentiate Progressive Disease from Treatment-Induced Effects in High-Grade (WHO Grade 3-4) Gliomas

BACKGROUND AND OBJECTIVES: Posttreatment radiologic deterioration of an irradiated high-grade (WHO grade 3-4) glioma (HGG) may be the result of true progressive disease or treatment-induced effects (TIE). Differentiation between these entities is of great importance but remains a diagnostic challenge. This study assesses the diagnostic value of conventional MRI characteristics to differentiate progressive disease from TIE in HGGs. METHODS: In this single-center, retrospective, consecutive cohort study, we included adults with a HGG who were treated with (chemo-)radiotherapy and subsequently developed a new or increasing contrast-enhancing lesion on conventional follow-up MRI. TIE and progressive disease were defined radiologically as stable/decreased for ≥6 weeks or Response Assessment in Neuro-Oncology progression and histologically as TIE without viable tumor or progressive disease. Two neuroradiologists assessed 21 preselected MRI characteristics of the progressive lesions. The statistical analysis included logistic regression to develop a full multivariable model, a diagnostic model with model reduction, and a Cohen kappa interrater reliability (IRR) coefficient. RESULTS: A total of 210 patients (median age 61 years, interquartile range 54-68, 189 male) with 284 lesions were included, of whom 141 (50%) had progressive disease. Median time to progressive disease was 2 (0.7-6.1) and to TIE 0.9 (0.7-3.5) months after radiotherapy. After multivariable modeling and model reduction, the following determinants prevailed: radiation dose (odds ratio [OR] 0.68, 95% CI 0.49-0.93), longer time to progression (TTP; OR 3.56, 95% CI 1.84-6.88), marginal enhancement (OR 2.04, 95% CI 1.09-3.83), soap bubble enhancement (OR 2.63, 95% CI 1.39-4.98), and isointense apparent diffusion coefficient (ADC) signal (OR 2.11, 95% CI 1.05-4.24). ORs >1 indicate higher odds of progressive disease. The Hosmer & Lemeshow test showed good calibration ( p = 0.947) and the area under the receiver operating characteristic curve was 0.722 (95% CI 0.66-0.78). In the glioblastoma subgroup, TTP, marginal enhancement, and ADC signal were significant. IRR analysis between neuroradiologists revealed moderate to near perfect agreement for the predictive items but poor agreement for others. DISCUSSION: Several characteristics from conventional MRI are significant predictors for the discrimination between progressive disease and TIE. However, IRR was variable. Conventional MRI characteristics from this study should be incorporated into a multimodal diagnostic model with advanced imaging techniques. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with irradiated HGGs, radiation dose, longer TTP, marginal enhancement, soap bubble enhancement, and isointense ADC signal distinguish progressive disease from TIE

Potential Adverse Outcomes of Shared Decision Making about Palliative Cancer Treatment: A Secondary Analysis of a Randomized Trial

Background: While shared decision making (SDM) is advocated for ethical reasons and beneficial outcomes, SDM might also negatively affect patients with incurable cancer. The current study explored whether SDM, and an oncologist training in SDM, are associated with adverse outcomes (i.e., patient anxiety, tension, helplessness/hopelessness, decisional uncertainty, and reduced fighting spirit). Design: A secondary analysis of a randomized clinical trial investigating the effects of SDM interventions in the context of advanced cancer. The relations between observed SDM (OPTION12), specific SDM elements (4SDM), oncologist SDM training, and adverse outcomes were analyzed. We modeled adverse outcomes as a multivariate phenomenon, followed by univariate regressions if significant. Results: In total, 194 patients consulted by 31 oncologists were included. In a multivariate analysis, observed SDM and adverse outcomes were significantly related. More specifically, more observed SDM in the consultation was related to patients reporting more tension (P = 0.002) and more decisional uncertainty (P = 0.004) at 1 wk after the consultation. The SDM element “informing about the options” was especially found to be related to adverse outcomes, specifically to more helplessness/hopelessness (P = 0.002) and more tension (P = 0.016) at 1 wk after the consultation. Whether the patient consulted an oncologist who had received SDM training or not was not significantly related to adverse outcomes. No relations with long-term adverse outcomes were found. Conclusions: It is important for oncologists to realize that for some patients, SDM may temporarily be associated with negative emotions. Further research is needed to untangle which, when, and how adverse outcomes might occur and whether and how burden may be minimized for patients. Observed shared decision making was related to more tension and uncertainty postconsultation in advanced cancer patients However, training oncologists in SDM did not affect adverse outcomes. Further research is needed to untangle which, when, and how adverse outcomes might occur and how burden may be minimized

Prevalence and Predictors of Physician-Patient Discordance in Prognostic Perceptions in Advanced Cancer

BACKGROUND: Discordance between physicians' and patients' prognostic perceptions in advanced cancer care threatens informed medical decision-making and end-of-life preparation, yet this phenomenon is poorly understood. We sought to: (1) describe the extent and direction of prognostic discordance, patients' prognostic information preferences in cases of prognostic discordance, and physicians' awareness of prognostic discordance; and (2) examine which patient, physician, and caregiver factors predict prognostic discordance. MATERIALS AND METHODS: Oncologists and advanced cancer patients (median survival ≤12 months; n = 515) from 7 Dutch hospitals completed structured surveys in a cross-sectional study. Prognostic discordance was operationalized by comparing physicians' and patients' perceptions of the likelihood of cure, 2-year mortality risk, and 1-year mortality risk. RESULTS: Prognostic discordance occurred in 20% (likelihood of cure), 24%, and 35% (2-year and 1-year mortality risk) of physician-patient dyads, most often involving patients with more optimistic perceptions than their physician. Among patients demonstrating prognostic discordance, the proportion who preferred not knowing prognosis varied from 7% (likelihood of cure) to 37% (1-year mortality risk), and 45% (2-year mortality risk). Agreement between physician-perceived and observed prognostic discordance or concordance was poor (kappa = 0.186). Prognostic discordance was associated with several patient factors (stronger fighting spirit, self-reported absence of prognostic discussions, an information source other than the healthcare provider), and greater physician-reported uncertainty about prognosis. CONCLUSION: Up to one-third of the patients perceive prognosis discordantly from their physician, among whom a substantial proportion prefers not knowing prognosis. Most physicians lack awareness of prognostic discordance, raising the need to explore patients' prognostic information preferences and perceptions, and to tailor prognostic communication