Symptom Monitoring and Health-Related Quality of Life in Non-metastatic Breast Cancer Patients:A Systematic Review

Purpose of Review: This review aims to investigate the effect of patient-reported symptom monitoring, defined as the process of active and systematic reporting of symptoms initiated by the patient, on the health-related quality of life of breast cancer patients. Recent Findings: Evidence suggests that online patient-reported symptom monitoring has the potential to positively impact the health-related quality of life of non-metastatic breast cancer patients, who are receiving systemic therapy. However, there is a lack of literature specifically addressing patient-reported symptom monitoring and HRQoL in metastatic breast cancer patients. Summary: Additional research on symptom monitoring and HRQoL in breast cancer patients at all stages and during all phases in the disease trajectory, including its impact on personalized treatment, is needed before integration into routine care can be considered. Validated questionnaires and current implementation frameworks should be used to accelerate knowledge development about symptom monitoring for patients and their healthcare professionals, ultimately enhancing symptom self-management and the efficiency of breast cancer healthcare in the future.</p

Use of in vitro human keratinocyte models to study the effect of cooling on chemotherapy drug-induced cytotoxicity

A highly distressing side-effect of cancer chemotherapy is chemotherapy-induced alopecia (CIA). Scalp cooling remains the only treatment for CIA, yet there is no experimental evidence to support the cytoprotective capacity of cooling. We have established a series of in vitro models for the culture of human keratinocytes under conditions where they adopt a basal, highly-proliferative phenotype thus resembling the rapidly-dividing sub-population of native hair-matrix keratinocytes. Using a panel of chemotherapy drugs routinely used clinically (docetaxel, doxorubicin and the active metabolite of cyclophosphamide 4-OH-CP), we demonstrate that although these drugs are highly-cytotoxic, cooling can markedly reduce or completely inhibit drug cytotoxicity, in agreement with clinical observations. By contrast, we show that cytotoxicity caused by specific combinatorial drug treatments cannot be adequately attenuated by cooling, supporting data showing that such treatments do not always respond well to cooling clinically. Importantly, we provide evidence that the choice of temperature may be critical in determining the efficacy of cooling in rescuing cells from drug-mediated toxicity. Therefore, despite their reductive nature, these in vitro models have provided experimental evidence for the clinically-reported cytoprotective role of cooling and represent useful tools for future studies on the molecular mechanisms of cooling-mediated cytoprotection

Going beyond (electronic) patient-reported outcomes: harnessing the benefits of smart technology and ecological momentary assessment in cancer survivorship research

Rapid developments in digital mobile and sensor technology have facilitated the active and passive collection of detailed, personalized data in increasingly affordable ways. Researchers may be familiar with the daily diary, portable computers, or the pedometer for the collection of patientreported outcomes (PRO) in cancer survivorship research. Such methods, termed ecological momentary assessment (EMA), have evolved with technological advances, e.g., collecting data or providing interventions (ecological momentary intervention, EMI) via apps or devices such as smartphones. These smart technology-adapted sEMA/ sEMI methods are more widely used in affective disorders or addictive behavior research but are currently still under-utilized in cancer survivorship research. A recent scoping review on the use of active EMA among cancer survivors identified twelve articles published between 1993 and 2018. Most of the included studies in that review used portable computers. This commentary will discuss the utility of sEMA/sEMI in cancer survivorship research and call for action to advance this area of science

SYMptom monitoring with Patient-Reported Outcomes using a web application among patients with Lung cancer in the Netherlands (SYMPRO-Lung):Study protocol for a stepped-wedge randomised controlled trial

Introduction Lung cancer and its treatment cause a wide range of symptoms impacting the patients’ health-related quality of life (HRQoL). The use of patient-reported outcomes (PRO) to monitor symptoms during and after cancer treatment has been shown not only to improve symptom management but also to improve HRQoL and overall survival (OS). Collectively, these results favour implementation of PRO-symptom monitoring in daily clinical care. However, these promising outcomes have been obtained under trial conditions in which patients were selected based on stringent inclusion criteria, and in countries with a dissimilar healthcare system than in the Netherlands. The primary aim of the SYMptom monitoring with Patient-Reported Outcomes using a web application among patients with Lung cancer in the Netherlands (SYMPRO-Lung) study is to evaluate the effect of PRO-symptom monitoring during and after lung cancer treatment on HRQoL in daily clinical practice. Secondary objectives include assessing the effect of PRO-symptom monitoring on progression-free survival, OS, the incidence and grade of PRO symptoms, medication adherence, implementation fidelity and cost-effectiveness. Methods and analysis The SYMPRO-Lung study is a prospective, multicentre trial with a stepped wedge cluster randomised design. Study participants (n=292 intervention, n=292 controls) include patients with lung cancer (stages I–IV) starting treatment with surgery, systemic treatment, targeted treatment and/or radiotherapy. Every participating centre will consecutively switch from the control period to the intervention period, in which patients report their symptoms weekly via an online tool. In the intervention group, we evaluate two alert approaches: the active and reactive approach. If the symptoms exceed a predefined threshold, an alert is sent to the healthcare provider (active approach) or to the patient (reactive approach). Both the control and intervention group complete HRQoL questionnaires at 4 time points: at baseline, 15 weeks, 6 months and 1-year post treatment). Differences in HRQoL between the groups will be compared using linear mixed modelling analyses, accounting for within-centre clustering, potential time effects and confounding. Ethics and dissemination The study protocol was approved by the Institutional Review Board and the Medical Ethics Committee of the Amsterdam UMC (under number NL 68440.029.18) and the institutional review boards of the participating study sites. The dissemination of the results will be conducted through publication in peer-reviewed journals and through scientific conferences. Trial registration number Trial register identifier: Netherlands Trial register Trial NL7897. Date of registration: 24 July 2019. https://www.trialregister.nl/trial/7897

Development of an updated, standardized, patient-centered outcome set for lung cancer

BACKGROUND: In 2016, the International Consortium for Health Outcomes Measurement (ICHOM) defined an international consensus recommendation of the most important outcomes for lung cancer patients. The European Health Outcomes Observatory (H2O) initiative aimed to develop an updated patient-centered core outcome set (COS) for lung cancer, to capture the patient perspective of the impact of lung cancer and (novel) treatments using a combination of patient-reported outcome (PRO) instruments and clinical data as a means to drive value-based health-care. MATERIAL AND METHODS: An international, expert team of patient representatives, multidisciplinary healthcare professionals, academic researchers and pharmaceutical industry representatives (n = 17) reviewed potential outcomes generated through literature review. A broader group of patients/patient representatives (n = 31), healthcare professionals / academic researchers (n = 83), pharmaceutical industry representatives (n = 26), and health authority representatives (n = 6) participated in a Delphi study. In two survey rounds, participants scored the relevance of outcomes from a preliminary list. The threshold for consensus was defined as ≥ 70 % of participants scoring an outcome as 'highly relevant'. In concluding consensus-meeting rounds, the expert multidisciplinary team finalized the COS. RESULTS: The preliminary list defined by the core group consisted of 102 outcomes and was prioritized in the Delphi procedure to 64. The final lung cancer COS includes: 1) case-mix factors (n = 27); 2) PROs related to health-related quality of life (HRQoL) (n = 25); 3) clinical outcomes (n = 12). Patient-reported symptoms beyond domains included in the ICHOM lung cancer set in 2016 were insomnia, nausea, vomiting, anxiety, depression, lack of appetite, gastric problems, constipation, diarrhoea, dysphagia, and haemoptysis. CONCLUSIONS: We will implement the lung cancer COS in Europe within the H2O initiative by collecting the outcomes through a combination of clinician-reported measures and PRO measures. The COS will support the adoption and reporting of lung cancer measures in a standardized way across Europe and empower patients with lung cancer to better manage their health care

The PRO-RCC study:a long-term PROspective Renal Cell Carcinoma cohort in the Netherlands, providing an infrastructure for ‘Trial within Cohorts’ study designs

BACKGROUND: Ongoing research in the field of both localized, locally advanced and metastatic renal cell carcinoma has resulted in the availability of multiple treatment options. Hence, many questions are still unanswered and await further research. A nationwide collaborative registry allows to collect corresponding data. For this purpose, the Dutch PROspective Renal Cell Carcinoma cohort (PRO-RCC) has been founded, for the prospective collection of long-term clinical data, patient reported outcome measures (PROMs) and patient reported experience measures (PREMs).METHODS: PRO-RCC is designed as a multicenter cohort for all Dutch patients with renal cell carcinoma (RCC). Recruitment will start in the Netherlands in 2023. Importantly, participants may also consent to participation in a 'Trial within cohorts' studies (TwiCs). The TwiCs design provides a method to perform (randomized) interventional studies within the registry. The clinical data collection is embedded in the Netherlands Cancer Registry (NCR). Next to the standardly available data on RCC, additional clinical data will be collected. PROMS entail Health-Related Quality of Life (HRQoL), symptom monitoring with optional ecological momentary assessment (EMA) of pain and fatigue, and optional return to work- and/or nutrition questionnaires. PREMS entail satisfaction with care. Both PROMS and PREMS are collected through the PROFILES registry and are accessible for the patient and the treating physician.TRIAL REGISTRATION: Ethical board approval has been obtained (2021_218) and the study has been registered at ClinicalTrials.gov (NCT05326620).DISCUSSION: PRO-RCC is a nationwide long-term cohort for the collection of real-world clinical data, PROMS and PREMS. By facilitating an infrastructure for the collection of prospective data on RCC, PRO-RCC will contribute to observational research in a real-world study population and prove effectiveness in daily clinical practice. The infrastructure of this cohort also enables that interventional studies can be conducted with the TwiCs design, without the disadvantages of classic RCTs such as slow patient accrual and risk of dropping out after randomization.</p

Quality of life after patient-initiated vs physician-initiated response to symptom monitoring:the SYMPRO-Lung trial

BackgroundPrevious studies using patient-reported outcomes measures (PROMs) to monitor symptoms during and after (lung) cancer treatment used alerts that were sent to the health-care provider, although an approach in which patients receive alerts could be more clinically feasible. The primary aim of this study was to compare the effect of weekly PROM symptom monitoring via a reactive approach (patient receives alert) or active approach (health-care provider receives alert) with care as usual on health-related quality of life (HRQOL) at 15 weeks after start of treatment in lung cancer patients.MethodsThe SYMPRO–Lung trial is a multicenter randomized controlled trial using a stepped wedge design. Stage I-IV lung cancer patients in the reactive and active groups reported PROM symptoms weekly, which were linked to a common alerting algorithm. HRQOL was measured by the EORTC QLQ-C30 at baseline and after 15 weeks. Linear regression analyses and effect size estimates were used to assess mean QOL–C30 change scores between groups, accounting for confounding.ResultsA total of 515 patients were included (160 active group, 89 reactive group, 266 control group). No differences in HRQOL were observed between the reactive and active group (summary score: unstandardized beta [B] = 0.51, 95% confidence interval [CI] = -3.22 to 4.24, Cohen d effect size [ES] = 0.06; physical functioning: B = 0.25, 95% CI = -5.15 to 4.64, ES = 0.02). The combined intervention groups had statistically and clinically significantly better mean change scores on the summary score (B = 4.85, 95% CI = 1.96 to 7.73, ES = 0.57) and physical functioning (B = 7.00, 95% CI = 2.90 to 11.09, ES = 0.71) compared with the control group.ConclusionsWeekly PRO symptom monitoring statistically and clinically significantly improves HRQOL in lung cancer patients. The logistically less intensive, reactive approach may be a better fit for implementation

Minimal added value of wetting hair before scalp cooling to prevent chemotherapy-induced alopecia in cancer patients — results from the Dutch Scalp Cooling Registry

Purpose: Preventing chemotherapy-induced alopecia (CIA) is related to the degree of temperature reduction during scalp cooling. Wetting hair before scalp cooling reduces the scalp skin temperature. This observational study investigated the effects of wetting hair before scalp cooling on preventing CIA and on tolerance in cancer patients. Methods: This Dutch multi-center cohort study comprised 1825 patients receiving ≥1 cycle of docetaxel (D), 5-fluorouracil-epirubicin-cyclophosphamide (FEC), 5-fluorouracil-epirubicin-cyclophosphamide-docetaxel (FECD), paclitaxel (P), or paclitaxel-carboplatin (PC). Patients underwent scalp cooling with wet or dry hair. Primary and secondary outcomes were the effects of wetting hair on head cover use and tolerance, respectively. Results: None of the associations between wetting hair and head cover use in patients on D, FEC, P, or PC was significant; however, results all tended to be in favor of wetting hair. For FECD, univariate (p=0.005; OR=1.6; CI=1.1–2.1) and multivariable associations (p=0.007; OR=1.8; CI=1.2-2.6) were significant. Scalp cooling discontinuation due to intolerance differed significantly between groups that wetted hair or not (3% and 1% respectively; p=0.034). Conclusion: In a large patient group with mainly a European hair type and a high hair mass, no convincing evidence was found whether wetting hair prior to scalp cooling contributes to better prevention of CIA. Since it is argued that a higher reduction in scalp skin temperature by wetting hair contributes positively to scalp cooling efficacy, only a randomized controlled trial can provide an ultimate conclusion at the highest level of evidence. Until that time, healthcare professionals have to take into account that wetting hair may introduce lower compliance to the scalp cooling procedure