What patients with advanced cancer experience as helpful in navigating their life with a long-term response: a qualitative study.

PURPOSE: Despite improved survival for people with advanced cancer due to new medical treatments, a growing group of long-term responders (LTRs) has to learn to live with uncertainties that affect several life domains. At the core of their experience, they neither feel like a patient nor feel healthy. Despite growing awareness of LTRs' experiences, learning more about how they cope with their long-term response can provide insight into how to best support them. Our study aimed to gain a deeper understanding what LTRs experience as helpful in navigating life with a long-term response. METHODS: We conducted an exploratory qualitative study using thematic data analysis. Semi-structured in-depth interviews were conducted with 17 participants with advanced melanoma or lung cancer with confirmed response or long-term stable disease while on immuno- or targeted therapy. RESULTS: LTRs reported several strategies to navigate life with a long-term response, for example, by involving the social environment, seeing uncertainty as an opportunity, and being present in the moment. This helped them to reclaim a sense of control, alter their perspective, and reshape their lives according to their values. CONCLUSION: Using different coping strategies enables LTRs to acknowledge both their sick and healthy side. Striking a healthy balance between being oriented on feeling sick or feeling healthy can help LTRs and their close others to navigate life with a long-term response. Healthcare professionals can provide support by recognizing whether LTRs are oriented at feeling sick or healthy, and by actively involving close others during medical appointments.

Living in the twilight zone: a qualitative study on the experiences of patients with advanced cancer obtaining long-term response to immunotherapy or targeted therapy.

PURPOSE: The introduction of immunotherapy and targeted therapy has drastically improved the life expectancy of patients with advanced cancer. Despite improved survival, obtaining long-term response can be highly distressing and comes with uncertainties that affect several life domains. The aim of this study is to gain a deeper understanding of long-term responders' lived experiences with obtaining long-term response to immunotherapy or targeted therapy. METHODS: We conducted an exploratory qualitative study using thematic data analysis. Semi-structured in-depth interviews were conducted with 17 patients with advanced melanoma or lung cancer who had a confirmed response to or long-term stable disease while on immunotherapy or targeted therapy. RESULTS: Long-term responders are living in a twilight zone, where they neither feel like a patient, nor feel healthy. This impacts their self-image, interactions with their social environment, and feelings of uncertainty. Due to their uncertain life perspective, long-term responders are going back and forth between hope and despair, while they are longing for their 'old' life, several barriers, such as protective behavior of the social environment, force them to adjust to a life with cancer. CONCLUSION: Long-term responders are facing many challenges, such as searching for a renewed identity, dealing with ongoing uncertainty, and having to adapt to a new normal. This emphasizes the importance of providing this new patient group with tailored information and support. IMPLICATIONS FOR CANCER SURVIVORS: Healthcare professionals can support patients by normalizing their feelings and providing space for varying emotions. Using patient-tailored scan frequencies could help temper fear of progression.

Frailty and checkpoint inhibitor toxicity in older patients with melanoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) that range from mild to life-threatening. Age itself does not seem to be a predictor for the occurrence of irAEs. It is unknown whether frailty plays a role in the occurrence of irAEs. Therefore, the authors assessed whether irAEs and their sequelae occur more often in frail patients than in fit patients according to the Geriatric 8 (G8) assessment. METHODS: Patients with melanoma aged 70 years and older who were about to start ICI therapy and were screened with the G8 assessment were enrolled in this prospective, observational study. Patients were classified by the G8 as either fit or frail. The primary outcome was the occurrence of grade ≥3 irAEs. RESULTS: In total, 92 patients were included for statistical analyses, 26 (29%) of whom were classified as frail. Grade ≥3 irAEs occurred in 20% of patients. There was no significant difference in the occurrence of grade ≥3 irAEs between fit and frail patients (17% vs 27%; P = .26). Frail patients were admitted to the hospital because of irAEs significantly more often than fit patients (29% vs 54%; P = .02) and showed a trend toward increased length of hospitalization (5 vs 8 days; P = .06) and more frequent use of immunosuppressants or ICI discontinuation for irAEs (36% vs 58%; P = .06). CONCLUSIONS: Although frailty appears to be unrelated to the occurrence of severe irAEs, it is an indicator of irAE-related adverse sequelae, such as hospital admission. Screening for frailty can be of added value in the shared decision-making process for older patients who qualify for ICI treatment.

Predicting Anxiety in Hospitalized Cancer Patients.

CONTEXT: Anxiety in patients with cancer is highly prevalent; yet it remains underestimated and inadequately assessed. Little is known about predictors for anxiety in hospitalized patients with cancer. Insight in predictors should improve recognition and enable a targeted approach. OBJECTIVES: To determine the prevalence of anxiety and predictors for anxiety in hospitalized patients with cancer at different stages of disease. METHODS: A cross-sectional analysis of patients with cancer admitted to the Utrecht University Medical Center in 2015-2018 was conducted. The Utrecht Symptom Diary, an adapted Dutch version of the Edmonton Symptom Assessment System, was used to assess symptom burden on a numeric rating scale (0 = no symptom and 10 = worst possible symptom). Scores ≥4 were considered clinically relevant. All patients completed the Utrecht Symptom Diary as part of routine care. The first questionnaire after admission was selected. Using multivariable linear regression, the predictive value of potential predictors on anxiety was analyzed. RESULTS: In total, 2144 patients were included, of which 22% reported clinically relevant anxiety. The prevalence of anxiety was highest (36%) in patients receiving symptom-directed palliation only. In the total group, female gender, younger age, depressed mood, sleeping problems, dyspnea, and cancer of the head and neck were predictive of anxiety. Throughout all stages of disease, depressed mood was consistently the strongest predictor. CONCLUSION: We found a high prevalence of anxiety in hospitalized patients with cancer. It is recommended to explore anxiety in hospitalized patients with cancer, in particular when they experience depressed mood. Structural use of a symptom diary during hospitalization facilitates the recognition of anxiety and concurrent symptoms.

Predictive value of each geriatric assessment domain for older patients with cancer: A systematic review.

BACKGROUND: A geriatric assessment (GA) is increasingly used to help guide treatment decisions in older patients with cancer. However, there is no consensus regarding which domains should be included in the GA. In addition, the field of geriatric oncology moves very fast and as a result many new studies have been published since the last review in 2015. Therefore, the objective of this systematic review is to evaluate which domains of the GA could predict patient-related treatment outcomes of older patients with cancer and thereby should be included in a GA. METHODS: A systematic literature search was performed for publications in English or Dutch between September 2006 and July 2017 addressing the association between individual domains of the GA and mortality, postoperative complications, or systemic treatment-related outcomes in older patients with cancer. RESULTS: Eight different domains were evaluated in 46 publications, namely functional status, nutritional status, cognition, mood, physical function, fatigue, social support, and falls. All eight domains were predictive for at least one of the investigated outcomes but the results were quite variable across studies. Physical function and nutritional status were the domains most often associated with mortality and systemic treatment-related outcomes, and the domain physical function was most often associated with postoperative complications. CONCLUSION: Overall, this review demonstrates that the GA should minimally consist of physical function and nutritional status, when the aim is to predict patients-related outcomes of older patients with cancer, although the results are quite heterogeneous. For the other domains, the findings are too inconsistent to draw conclusions about their overall predictive ability.

Platelet function is disturbed by the angiogenesis inhibitors sunitinib and sorafenib, but unaffected by bevacizumab.

INTRODUCTION: At the clinical introduction of antiangiogenic agents as anticancer agents, no major toxicities were expected as merely just endothelial cells (ECs) in tumors would be affected. However, several (serious) toxicities became apparent, of which underlying mechanisms are largely unknown. We investigated to what extent sunitinib (multitargeted antiangiogenic tyrosine kinase inhibitor (TKI)), sorafenib (TKI) and bevacizumab [specific antibody against vascular endothelial growth factor (VEGF)] may impair platelet function, which might explain treatment-related bleedings. MATERIALS AND METHODS: In vitro, the influence of sunitinib, sorafenib, and bevacizumab on platelet aggregation, P-selectin expression and fibrinogen binding, platelet-EC interaction, and tyrosine phosphorylation of c-Src was studied by optical aggregation, flow cytometry, real-time perfusion, and western blotting. Ex vivo, platelet aggregation was analyzed in 25 patients upon sunitinib or bevacizumab treatment. Concentrations of sunitinib, VEGF, and platelet and EC activation markers were measured by LC-MS/MS and ELISA. RESULTS: In vitro, sunitinib and sorafenib significantly inhibited platelet aggregation (20 µM sunitinib: 71.3%, p < 0.001; 25 µM sorafenib: 55.8%, p = 0.042). Sorafenib and sunitinib significantly inhibited P-selectin expression on platelets. Exposure to both TKIs resulted in a reduced tyrosine phosphorylation of c-Src. Ex vivo, within 24 h sunitinib impaired platelet aggregation (83.0%, p = 0.001, N = 8). Plasma concentrations of sunitinib, VEGF, and platelet/EC activation markers were not correlated with disturbed aggregation. In contrast, bevacizumab only significantly impaired platelet aggregation in vitro at high concentrations, but not ex vivo. CONCLUSION: Sunitinib significantly inhibits platelet aggregation in patients already after 24 h of first administration, whereas bevacizumab had no effect on aggregation. These findings may explain the clinically observed bleedings during treatment with antiangiogenic TKIs.

Strategies for assessing and managing the adverse events of sorafenib and other targeted therapies in the treatment of renal cell and hepatocellular carcinoma: recommendations from a European nursing task group.

PURPOSE: As a group of European nurses familiar with treating patients with renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) using targeted/chemo- therapies, we aimed to review strategies for managing adverse events (AEs) associated with one targeted therapy, sorafenib. METHOD: Focusing on the AEs we considered the most difficult to manage (hand-foot skin reaction [HFSR], diarrhoea, fatigue and mucositis/stomatitis), we reviewed the literature to identify strategies relevant to sorafenib. Given the paucity of published work, this included strategies concerning targeted agents in general. This information was supplemented by considering the wider literature relating to management of these AEs in other tumour types and similar toxicities experienced during conventional anti-cancer therapy. Together with our own experience, this information was used to compile an AE management guide to assist nurses caring for patients receiving sorafenib. RESULTS: Our collated experience suggests the most commonly reported AEs with sorafenib and other targeted agents are HFSR, diarrhoea, fatigue, rash and mucositis/stomatitis; these generally have an acute (appearing at ∼0-1 months) or delayed onset (appearing at ∼3 months). Most management strategies in the literature were experience-based rather than arising from controlled studies. However, strategies based on controlled studies are available for HFSR and mucositis/stomatitis. CONCLUSIONS: Evidence, especially from controlled studies, is sparse concerning management of AEs associated with sorafenib and other targeted agents in RCC/HCC. However, recommendations can be made based on the literature and clinical experience that encompasses targeted and conventional therapies, particularly in the case of non-specific toxicities e.g. diarrhoea and fatigue.