Monitoring Adolescent and Young Adult Patients With Cancer via a Smart T-Shirt: Prospective, Single-Cohort, Mixed Methods Feasibility Study (OncoSmartShirt Study).

Background: Wearables that measure vital parameters can be potential tools for monitoring patients at home during cancer treatment. One type of wearable is a smart T-shirt with embedded sensors. Initially, smart T-shirts were designed to aid athletes in their performance analyses. Recently however, researchers have been investigating the use of smart T-shirts as supportive tools in health care. In general, the knowledge on the use of wearables for symptom monitoring during cancer treatment is limited, and consensus and awareness about compliance or adherence are lacking. objectives: The aim of this study was to evaluate adherence to and experiences with using a smart T-shirt for the home monitoring of biometric sensor data among adolescent and young adult patients undergoing cancer treatment during a 2-week period. Methods: This study was a prospective, single-cohort, mixed methods feasibility study. The inclusion criteria were patients aged 18 to 39 years and those who were receiving treatment at Copenhagen University Hospital - Rigshospitalet, Denmark. Consenting patients were asked to wear the Chronolife smart T-shirt for a period of 2 weeks. The smart T-shirt had multiple sensors and electrodes, which engendered the following six measurements: electrocardiogram (ECG) measurements, thoracic respiration, abdominal respiration, thoracic impedance, physical activity (steps), and skin temperature. The primary end point was adherence, which was defined as a wear time of >8 hours per day. The patient experience was investigated via individual, semistructured telephone interviews and a paper questionnaire. Results: A total of 10 patients were included. The number of days with wear times of >8 hours during the study period (14 d) varied from 0 to 6 (mean 2 d). Further, 3 patients had a mean wear time of >8 hours during each of their days with data registration. The number of days with any data registration ranged from 0 to 10 (mean 6.4 d). The thematic analysis of interviews pointed to the following three main themes: (1) the smart T-shirt is cool but does not fit patients with cancer, (2) the technology limits the use of the smart T-shirt, and (3) the monitoring of data increases the feeling of safety. Results from the questionnaire showed that the patients generally had confidence in the device. Conclusions: Although the primary end point was not reached, the patients' experiences with using the smart T-shirt resulted in the knowledge that patients acknowledged the need for new technologies that improve supportive cancer care. The patients were positive when asked to wear the smart T-shirt. However, technical and practical challenges in using the device resulted in low adherence. Although wearables might have potential for home monitoring, the present technology is immature for clinical use.

Sexuality, intimacy, and body image among adolescents and young adults with cancer: a qualitative, explorative study.

AIM: The aim of this study was threefold: (1) to explore Danish adolescents and young adults' (AYAs) thoughts concerning sexual health particularly focusing on sexuality, intimacy, and body image throughout a cancer trajectory, (2) to investigate how AYAs experience healthcare professionals address of- and respond to sexual health issues, and (3) to identify AYAs' suggestions on how to support conversation about sexual health. METHODS: A qualitative, single-center study was conducted, including AYAs (18-29 years) diagnosed with cancer recruited at the University Hospital of Copenhagen, Rigshospitalet. Individual semi-structured interviews were conducted from January-February 2023, recorded, transcribed verbatim, and analyzed using thematic analysis. RESULTS: Twelve participants were interviewed, aged 20-29; five were diagnosed with hematological- and seven with oncological cancer. Our analyses yielded three themes: (1) sexuality and body image as part of the identity, (2) excluding relatives in conversations about sexual health, and (3) uncertainty how to discuss sexual health with healthcare professionals. Finally, the AYAs' suggestions to support conversations about sexual health were organized into six thematic categories. CONCLUSION: In this study, participants experienced altered sexual subsequent impacts on body image and self-esteem during their cancer trajectory. While some adapted to these changes, discussing them with healthcare providers was difficult, especially in the presence of relatives, as the AYAs wanted to shield them from additional concerns. To enhance support, AYAs suggest regular discussions on sexual health and the use of a dialog tool by healthcare professionals.

Development of an App for Symptom Management in Women With Breast Cancer Receiving Maintenance Aromatase Inhibitors: Protocol for a Mixed Methods Feasibility Study.

BACKGROUND: Patients with postmenopausal nonmetastatic estrogen receptor-positive breast cancer often experience a reduced quality of life after primary treatment. The disease and treatment trajectory consists of surgery followed by chemotherapy or radiation therapy. Upon this, maintenance hormone therapy with an aromatase inhibitor can result in several physical and psychosocial symptoms. Optimal symptom control during maintenance therapy is central to maintaining the patient's quality of life. OBJECTIVE: This study aims to (1) develop an electronic symptom management tool for patients with postmenopausal early breast cancer receiving maintenance aromatase inhibitors with an endocrine aspect and (2) assess the feasibility, acceptability, and usability of the pilot version of the Bone@BC app. Furthermore, longitudinally, symptom prevalence and quality of life for patients with postmenopausal nonmetastatic estrogen receptor-positive breast cancer will be explored. METHODS: This study follows a multistage research plan. In stage 1, a systematic literature review to establish an overview of aromatase inhibitor-related symptoms reported by postmenopausal women with nonmetastatic estrogen receptor-positive breast cancer will be completed. In stage 2, a comprehensive overview of symptoms related to aromatase inhibitors (letrozole, exemestane, and anastrozole) will be performed (eg, by reviewing medical leaflets and guidelines). In stage 3, an electronic app with a user-friendly Patient Concern Inventory list to comprise symptoms and concerns will be developed. Last, in stage 4, a convergent mixed methods feasibility study of the pilot version of the Bone@BC app will be conducted. A total of 45 patients with postmenopausal nonmetastatic estrogen receptor-positive breast cancer will use the app daily for symptom identification and respond to 6 serial patient-reported outcome measurements for 12 weeks. Finally, semistructured interviews will be performed. The primary outcome includes consent rate, attrition rate, retention rates, technical issues, and adherence, assessed using preestablished criteria on feasibility and a mixed methods approach for exploring acceptability. A patient advisory board consisting of 5 women with breast cancer is recruited to include their perspectives and experiences in the planning, organization, implementation, and dissemination of the research throughout the project. RESULTS: At the time of submitting this paper (January 2024), a total of 23 patients have been included in the stage 2 medical audit over the recruitment period of 3 months (November 2022 to February 2023), and 19 patients have been enrolled in stage 2, the semistructured patient interviews. CONCLUSIONS: This protocol describes a study investigating the feasibility, acceptability, and usability of the symptom management tool Bone@BC developed for patients with breast cancer with an endocrine aspect. TRIAL REGISTRATION: ClinicalTrails.gov NCT05367830; https://clinicaltrials.gov/ct2/show/NCT05367830. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49549.

Health-related Quality of Life in Patients with Previously Treated Advanced Urothelial Carcinoma from EV-301: A Phase 3 Trial of Enfortumab Vedotin Versus Chemotherapy.

BACKGROUND AND OBJECTIVE: In comparison to chemotherapy, enfortumab vedotin (EV) prolonged overall survival in patients with previously treated advanced urothelial carcinoma in EV-301. The objective of the present study was to assess patient experiences of EV versus chemotherapy using patient-reported outcome (PRO) analysis of health-related quality of life (HRQoL). METHODS: For patients in the phase 3 EV-301 trial randomized to EV or chemotherapy we assessed responses to the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, weekly for the first 12 wk, and then every 12 wk until discontinuation. We analyzed the QLQ-C30 change from baseline to week 12, the confirmed improvement rate, and the time to improvement or deterioration. KEY FINDINGS AND LIMITATIONS: Baseline PRO compliance rates were 91% for the EV arm (n = 301) and 89% for the chemotherapy arm (n = 307); the corresponding average rates from baseline to week 12 were 70% and 67%. Patients receiving EV versus chemotherapy had reduced pain (difference in change from baseline to week 12: -5.7, 95% confidence interval [CI] -10.8 to -0.7; p = 0.027) and worsening appetite loss (7.3, 95% CI 0.90-13.69; p = 0.026). Larger proportions of patients in the EV arm reported HRQoL improvement from baseline than in the chemotherapy arm; the odds of a confirmed improvement across ten QLQ-C30 function/symptom scales were 1.67 to 2.76 times higher for EV than for chemotherapy. Patients in the EV arm had a shorter time to first confirmed improvement in global health status (GHS)/QoL, fatigue, pain, and physical, role, emotional, and social functioning (all p < 0.05). EV delayed the time to first confirmed deterioration in GHS/QoL (p = 0.027), but worsening appetite loss occurred earlier (p = 0.009) in comparison to chemotherapy. CONCLUSIONS AND CLINICAL IMPLICATIONS: HRQoL with EV was maintained, and deterioration in HRQoL was delayed with EV in comparison to chemotherapy. Better results with EV were reported for some scales, with the greatest difference observed for pain. These findings reinforce the EV safety and efficacy outcomes and benefits observed in EV-301. PATIENT SUMMARY: Patients with previously treated advanced cancer of the urinary tract receiving the drug enfortumab vedotin maintained their HRQoL in comparison to patients treated with chemotherapy. The EV-301 trial is registered on ClinicalTrials.gov as NCT03474107 and on EudraCT as 2017-003344-21.

Experiences with Wearable Sensors in Oncology during Treatment: Lessons Learned from Feasibility Research Projects in Denmark.

BACKGROUND: The fraction of elderly people in the population is growing, the incidence of some cancers is increasing, and the number of available cancer treatments is evolving, causing a challenge to healthcare systems. New healthcare tools are needed, and wearable sensors could partly be potential solutions. The aim of this case report is to describe the Danish research experience with wearable sensors in oncology reporting from three oncological wearable research projects. CASE STUDIES: Three planned case studies investigating the feasibility of different wearable sensor solutions during cancer treatment are presented, focusing on study design, population, device, aim, and planned outcomes. Further, two actual case studies performed are reported, focusing on patients included, data collected, results achieved, further activities planned, and strengths and limitations. RESULTS: Only two of the three planned studies were performed. In general, patients found the technical issues of wearable sensors too challenging to deal with during cancer treatment. However, at the same time it was demonstrated that a large amount of data could be collected if the framework worked efficiently. CONCLUSION: Wearable sensors have the potential to help solve challenges in clinical oncology, but for successful research projects and implementation, a setup with minimal effort on the part of patients is requested.

DaBlaCa-17: nationwide observational study in Denmark on survival before and after implementation of neoadjuvant chemotherapy prior to cystectomy for muscle-invasive bladder cancer.

OBJECTIVE: To investigate the impact of neoadjuvant chemotherapy implementation with gemcitabine-cisplatin on survival outcomes for patients with muscle-invasive bladder cancer in Denmark. MATERIALS AND METHODS: Data were collected on all patients in Denmark undergoing radical cystectomy who were potential candidates for neoadjuvant chemotherapy from 2010 to 2015 (n = 851). A cohort before the implementation of neoadjuvant chemotherapy (Cohort 2010-12) was compared with a cohort after implementation (Cohort 2013-15). Patients in Cohort 2013-15 receiving neoadjuvant chemotherapy (+NAC, n = 213) were compared with patients in Cohort 2013-15 not receiving neoadjuvant chemotherapy (-NAC, n = 139). Pathological results after radical cystectomy and oncological outcomes were compared between the study cohorts. Overall survival, disease-free survival, and disease-specific survival were compared with Kaplan-Meier plots and with univariable and multivariable Cox regression. Kaplan-Meier estimates of overall survival were also performed separately for treating hospital and for pathological stage. RESULTS: Pathological T0 (pT0) was more frequent in patients who received neoadjuvant chemotherapy: 34% versus 18% when comparing Cohort 2013-15 with Cohort 2010-12 (p < 0.001), and 46% versus 16% in +NAC compared with -NAC (p < 0.001). Overall survival, disease-free survival, and disease-specific survival at 5 years after cystectomy were not improved in Cohort 2013-15 compared with Cohort 2010-12 with adjusted hazard ratios of 1.11 (95% confidence interval [CI]: 0.87-1.43), 1.02 (95% CI: 0.81-1.29), and 1.06 (95% CI: 0.80-1.41), respectively. CONCLUSIONS: This observational study found no improved survival in a national cohort of patients with muscle-invasive bladder cancer undergoing radical cystectomy after implementation of NAC. However, reservations should be made regarding the study design and the true effect of NAC on survival outcomes.

Glomerular filtration rate measurement during platinum treatment for urothelial carcinoma: optimal methods for clinical practice.

BACKGROUND: We assessed the accuracy of four estimated glomerular filtration rate (eGFR) methods: MDRD, Cockcroft-Gault, CKD-EPI, and Wright. METHOD: The four methods were compared to measure GFR (mGFR) in patients with urothelial urinary tract cancer (T2-T4bNxMx) receiving platinum-based chemotherapy at Rigshospitalet, Copenhagen, from January 2019 to December 2021. Using standardized assays, creatinine values were measured, and mGFR was determined using Technetium-99 m diethylenetriaminepentaacetic acid (Tc-99 m-DTPA) or Cr-51-ethylenediaminetetraacetic acid (Cr-51-EDTA) plasma clearance. Patients (n = 146) with both mGFR and corresponding creatinine values available were included (n = 345 measurements). RESULTS: The CKD-EPI method consistently demonstrated superior accuracy, with the lowest Total Deviation Index of 21.8% at baseline and 22.9% for all measurements compared to Wright (23.4% /24.1%), MDRD (26.2%/25.5%), and Cockcroft-Gault (25.x%/25.1%). Bland Altman Limits of agreement (LOA) ranged from - 32 ml/min (Cockcroft-Gault) to + 33 ml/min (MDRD), with CKD-EPI showing the narrowest LOA (- 27 ml/min to + 24 ml/min and lowest bias (0.3 ml/min). Establishing an eGFR threshold at 85 ml/min-considering both the lower limit of agreement (LOA) and the minimum cisplatin limit at 60 ml/min-allows for the safe omission of mGFR in 30% of patients in this cohort. CONCLUSION: CKD-EPI equation emerged as the most suitable for estimating kidney function in this patient group although not meeting benchmark criteria. We recommend its use for initial assessment and ongoing monitoring, and suggest mGFR for patients with a CKD-EPI estimated GFR below 85 ml/min. This approach could reduce costs and decrease laboratory time for 30% of our UC patients.

Machine learning applied in patient-reported outcome research-exploring symptoms in adjuvant treatment of breast cancer.

BACKGROUND: Patient-reported outcome (PRO) data may help us better understand the life of breast cancer patients. We have previously collected PRO data in a national Danish breast cancer study in patients undergoing adjuvant chemotherapy. The aim of the present post-hoc explorative study is to apply Machine Learning (ML) algorithms using permutation importance to explore how specific PRO symptoms influence nonadherence to six cycles of planned adjuvant chemotherapy in breast cancer patients. METHODS: We here investigate ePRO-data from the 347 patients. The ePRO presented 42 PROCTCAE questions on 25 symptoms. Patients completed the ePRO before each cycle of chemotherapy. Number of patients with completion of the scheduled six cycles of chemotherapy were registered. Two ML models were applied. One aimed at discovering the individual relative importance of the different questions in the dataset while the second aimed at discovering the relationships between the questions. Permutation importance was used. RESULTS: Out of 347 patients 238 patients remained in the final dataset, 15 patients dropped out. Two symptoms: aching joints and numbness/tingling, were the most important for dropout in the final dataset, each with an importance value of about 0.04. Model's average ROC-AUC-score being 0.706. In the second model a low performance score made the results very unreliable. CONCLUSION: In conclusion, this explorative data analysis using ML methodologies in an ePRO dataset from a population of women with breast cancer treated with adjuvant chemotherapy unravels that the symptoms aching joints and numbness/tingling could be important for drop out of planned adjuvant chemotherapy.

Patient-reported outcomes used actively in cancer patients undergoing antineoplastic treatment: A mini-review of the Danish landscape.

Introduction: Many studies using Patient-reported outcomes (PRO) data have been conducted to monitor symptoms and health-related quality of life during follow-up after cancer treatment. However new ways of using (e)PROs have emerged. We aimed to explore the Danish landscape of the use of PRO in a research setting, where PRO is used actively in cancer patients undergoing treatment, and give an overview of how it is embraced by patients and clinicians. Methods and materials: A literature search was performed in June 2023, using the keywords Denmark, cancer, and patient-reported outcomes. An expert on literature searches identified the search terms, and double screening was performed at both abstract and screening levels and full-text stage. The software tool Covidence was used. Results: 467 articles were retrieved and 19 studies were included. They described the type of ePRO instrument used and the application of active ePRO i.e. a dialogue tool in the clinical encounter, release of alerts to clinicians, and enhancement of self-management. Finally, a development in the use of active ePROs over time is elucidated and we show how it is embraced by patients and clinicians. Conclusion: This mini-review gives an overview of how ePRO solutions are tested in oncological research in Denmark and embraced by patients and clinicians. ePRO solutions in a Danish setting seem well-suited for self-management. However, if more impact is warranted, clinicians need to engage in reviewing and using ePROs. Moreover, for successful implementation, the integration of ePROs in electronic health records must be supported by IT specialists and management.

Patient Engagement in Research Scale (PEIRS-22): Danish translation, applicability, and user experiences.

BACKGROUND: Patient and Public Involvement (PPI) in health research is gaining increased attention and acceptance worldwide. Reliable measurements are crucial to accurately assess, monitor, and evaluate patient involvement efforts in research. The Patient Engagement in Research Scale (PEIRS-22) measures meaningful patient and family caregiver engagement in research. This study focuses on three primary objectives: (1) translation of the PEIRS-22 from English to Danish, followed by linguistic validation and cultural adaptation; (2) assessing the applicability of the Danish PEIRS-22; and (3) focus group interviews to explore the user experiences of PPI. METHODS: A three-phase multi-method study was conducted. In phase one, the PEIRS-22 was translated, linguistically validated and culturally adapted to Danish. In phase two individuals from three distinct patient cancer advisory boards responded to the Danish version of PEIRS-22 to assess its applicability. Three focus group interviews were conducted in phase three, involving individuals from three patient cancer advisory boards. RESULTS: The translation process resulted in a Danish version of PEIRS-22, conceptually and culturally equivalent to the English version. Overall, among individuals of the three advisory boards (n = 15) the applicability was found to be satisfactory, with no missing data and all items completed. The total PEIRS-22 score among the three advisory boards was 85.2 out of a possible 100, with higher scores indicating greater meaningful involvement. A nested sample of the three patient cancer advisory boards (n = 9) participated in focus group interviews. The analysis yielded four themes: (1) The Danish PEIRS-22 captured the intended cultural meaning and contributed to self-reflection, (2) Internal motivation is a driver for involvement (3), Involvement brought a personal sense of empowerment and (4) Meaningful involvement collaborations are fostered by a trustful atmosphere. CONCLUSIONS: The PEIRS-22 questionnaire has been translated, linguistically validated, and culturally adapted into Danish. We propose that the PEIRS-22 is now ready for use in Danish populations. This study provides a Danish version of the questionnaire that can be used to develop patient-centred practices and foster meaningful involvement and collaborations between patients and researchers in the field of cancer research in Denmark. Personal benefits of participating in PPI can vary, and we recommend using PEIRS-22 in conjunction with a qualitative approach to better explore perspectives on meaningful involvement. TRIAL REGISTRATION: The study was registered prospectively on October 22, 2022, by the Danish Data Protection Agency (jr. nr. P-2022-528).

Patient and public involvement (PPI) in research can improve research practices by ensuring that patients' voices are heard. Individuals' lived experiences and unique viewpoints can contribute to refining research aims, ensuring they align with the needs and priorities of the target population. There is a growing interest in inviting patients into the research team as patient partners, for example, by establishing patient advisory boards. PPI can also involve caregivers and other stakeholders who are not usually thought of as members of the research team. For that reason, broadening our understanding of establishing meaningful PPI starts with measuring patient and family caregiver involvement. As such, the Patient Engagement In Research Scale (PEIRS-22) has been developed in the English language to measure meaningful patient and caregiver involvement. In this study, we aimed to (1) create a Danish version of the PEIRS-22 that respects any unique feature of Danish people, (2) assess the applicability of the Danish PEIRS-22, and (3) via focus-group interviews explore the user experiences of PPI. The patients and caregiver who were interviewed as part of the translation process expressed that the PEIRS-22 was easy to understand and captured the intended meanings. Fifteen other patient partners responded to the Danish version of PEIRS-22, and nine of them participated in the focus group interviews. One result was that creating a trusting and social atmosphere within the research group is important for promoting a personal sense of involvement.

Development of Quality of Life in Adolescents and Young Adults With Cancer Using a Patient Support Smartphone App: Prepost Interventional Study.

BACKGROUND: Adolescents and young adults often experience existential concerns in addition to side effects during a cancer trajectory, which they often carry alone. Thus, cohesion with other adolescents and young adults with cancer is essential but difficult due to the relatively small, widely dispersed nationwide population. In cocreation, a smartphone app has been developed and includes an information bank, a symptom tracker, and a social community platform, aiming to improve the quality of life (QoL) in this patient group. OBJECTIVE: This nationwide, multicenter study aimed to investigate the QoL in adolescents and young adults undergoing a cancer trajectory as they used the app for 6 weeks. METHODS: Via youth support initiatives, participants were recruited from hospitals in all regions of Denmark. Inclusion criteria were patients with cancer aged 15-29 years who either initiated any cancer treatment or started follow-up after cancer treatment within 30 days. Participants used the adolescents and young adults cancer app for 6 weeks. Before and after the 6 weeks of app use, they completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). The participants were divided into a treatment and a follow-up group for analysis. A high score for a functional scale or the global health or overall QoL represents a high or healthy level of functioning or high QoL, respectively; however, a high score for a symptom scale or item represents a high level of symptomatology. RESULTS: Overall, 81 participants were recruited. However, 4 participants did not answer the questionnaire and 6 participants did not use the app. In the treatment group (n=36), significant improvement was found in 2 domains: "Role functioning" (baseline median 33.33, IQR 16.67-83.33 vs 6 weeks median 66.67, IQR 33.33-83.33; P=.04) and "Pain" (baseline median 33.33, IQR 16.67-50.00 vs 6 weeks median 16.67, IQR 0.00-33.33; P=.04). The "Global health/Overall QoL" scale remained stable (baseline median 58.33, IQR 45.83-77.08 vs 6 weeks median 62.50, IQR 41.67-75.00; P=.25). In the follow-up group (n=35), significant improvement was found in 3 domains: "Physical functioning" (baseline median 79.23, IQR 73.33-93.33 vs 6 weeks median 82.86, IQR 73.33-100.00; P=.03), "Cognitive functioning" (baseline median 62.38, IQR 50.00-83.33 vs 6 weeks median 69.52, IQR 50.00-100.00; P=.02), and "Social functioning" (baseline median 76.19, IQR 50.00-100.00 vs 6 weeks median 85.71, IQR 83.33-100.00; P=.05), as well as in the "Global health/Overall QoL" scale (baseline median 57.14, IQR 83.33-100.00 vs 6 weeks median 75.0, IQR 62.91-85.73; P<.001). CONCLUSIONS: In this study, we found an improvement in specific QoL scales for both participants in treatment and follow-up when using the app for 6 weeks. The global health or overall QoL score improved significantly in the follow-up group. In the treatment group, it remained stable. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/10098.

Nucleotide excision repair deficiency is a targetable therapeutic vulnerability in clear cell renal cell carcinoma.

Due to a demonstrated lack of DNA repair deficiencies, clear cell renal cell carcinoma (ccRCC) has not benefitted from targeted synthetic lethality-based therapies. We investigated whether nucleotide excision repair (NER) deficiency is present in an identifiable subset of ccRCC cases that would render those tumors sensitive to therapy targeting this specific DNA repair pathway aberration. We used functional assays that detect UV-induced 6-4 pyrimidine-pyrimidone photoproducts to quantify NER deficiency in ccRCC cell lines. We also measured sensitivity to irofulven, an experimental cancer therapeutic agent that specifically targets cells with inactivated transcription-coupled nucleotide excision repair (TC-NER). In order to detect NER deficiency in clinical biopsies, we assessed whole exome sequencing data for the presence of an NER deficiency associated mutational signature previously identified in ERCC2 mutant bladder cancer. Functional assays showed NER deficiency in ccRCC cells. Some cell lines showed irofulven sensitivity at a concentration that is well tolerated by patients. Prostaglandin reductase 1 (PTGR1), which activates irofulven, was also associated with this sensitivity. Next generation sequencing data of the cell lines showed NER deficiency-associated mutational signatures. A significant subset of ccRCC patients had the same signature and high PTGR1 expression. ccRCC cell line-based analysis showed that NER deficiency is likely present in this cancer type. Approximately 10% of ccRCC patients in the TCGA cohort showed mutational signatures consistent with ERCC2 inactivation associated NER deficiency and also substantial levels of PTGR1 expression. These patients may be responsive to irofulven, a previously abandoned anticancer agent that has minimal activity in NER-proficient cells.

Impact of multimorbidity and polypharmacy on mortality after cancer: a nationwide registry-based cohort study in Denmark 2005-2017.

BACKGROUND: Concurrent chronic diseases and treatment hereof in patients with cancer may increase mortality. In this population-based study we examined the individual and combined impact of multimorbidity and polypharmacy on mortality, across 20 cancers and with 13-years follow-up in Denmark. MATERIALS AND METHODS: This nationwide study included all Danish residents with a first primary cancer diagnosed between 1 January 2005 and 31 December 2015, and followed until the end of 2017. We defined multimorbidity as having one or more of 20 chronic conditions in addition to cancer, registered in the five years preceding diagnosis, and polypharmacy as five or more redeemed medications 2-12 months prior to cancer diagnosis. Cox regression analyses were used to estimate the effects of multimorbidity and polypharmacy, as well as the combined effect on mortality. RESULTS: A total of 261,745 cancer patients were included. We found that patients diagnosed with breast, prostate, colon, rectal, oropharynx, bladder, uterine and cervical cancer, malignant melanoma, Non-Hodgkin lymphoma, and leukemia had higher mortality when the cancer diagnosis was accompanied by multimorbidity and polypharmacy, while in patients with cancer of the lung, esophagus, stomach, liver, pancreas, kidney, ovarian and brain & central nervous system, these factors had less impact on mortality. CONCLUSION: We found that multimorbidity and polypharmacy was associated with higher mortality in patients diagnosed with cancer types that typically have a favorable prognosis compared with patients without multimorbidity and polypharmacy. Multimorbidity and polypharmacy had less impact on mortality in cancers that typically have a poor prognosis.

The iBLAD study: patient-reported outcomes in bladder cancer during oncological treatment: a multicenter national randomized controlled trial.

BACKGROUND: Patient-reported outcomes (PROs) are getting widely implemented, but little is known of the impact of applying PROs in specific cancer diagnoses. We report the results of a randomized controlled trial (RCT) of the active use of PROs in patients with locally advanced or metastatic bladder cancer (BC) undergoing medical oncological treatment (MOT) with focus on determining the clinical effects of using PROs during chemo- or immunotherapy compared to standard of care. METHODS: We recruited patients from four departments of oncology from 2019 to 2021. Inclusion criteria were locally advanced or metastatic BC, initiating chemo- or immunotherapy. Patients were randomized 1:1 between answering selected PRO-CTCAE questions electronically once weekly with a built-in alert-algorithm instructing patients of how to handle reported symptoms as a supplement to standard of care for handling of side effects (intervention arm (IA)) vs standard procedure for handling of side effects (control arm (CA)). No real-time alerts were sent to the clinic when PROs exceeded threshold values. Clinicians were prompted to view the completed PROs in the IA at each clinical visit. The co-primary clinical endpoints were hospital admissions and treatment completion rate. Secondary endpoints were overall survival (OS), quality of life (EORTC's QLQ-C30 and QLQ-BLM30) and dose reductions. RESULTS: 228 patients with BC were included, 76% were male. 141 (62%) of the patients had metastatic disease. 51% of patients in the IA completed treatment vs. 56% of patients in the CA, OR 0.83 (95% CI 0.47-1.44, p = 0.51). 41% of patients in the IA experienced hospitalization vs. 32% in the CA, OR 1.48 (95% CI 0.83-2.65, p = 0.17). OS was comparable between the two arms (IA: median 22.3mo (95% CI 17.0-NR) vs. CA: median 23.1mo (95% CI 17.7-NR). Patient and clinician compliance was high throughout the study period (80% vs 94%). CONCLUSIONS: This RCT did not show an effect of PRO on completion of treatment, hospitalizations or OS for BC patients during MOT despite a high level of patient and clinician compliance. The lack of real-time response to alerts remains the greatest limitation to this study.

Aromatase Inhibitor-Related Symptoms Reported by Postmenopausal Women with Nonmetastatic, Estrogen Receptor-Positive Breast Cancer: A Systematic Review.

PURPOSE: The objective of this systematic review was to establish an overview of aromatase inhibitor-related symptoms reported by postmenopausal women with nonmetastatic, estrogen receptor-positive breast cancer. DATA SOURCES: Eight databases (PubMed, Cochrane, Cumulative Index to Nursing and Allied Health Literature [CINAHL], Ovid EMBASE, Ovid MEDLINE, PsycINFO, Scopus, and Web of Science) were searched for trials published between January 2004 and November 2021. Inclusion criteria were studies exploring patient-reported aromatase inhibitor-related symptoms in postmenopausal women with nonmetastatic estrogen receptor-positive breast cancer. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Mixed Method Appraisal Tool were used to rate the quality of the trials included. Of 325 full-text papers, 10 were included. Patient-reported symptoms were clustered by using the European Organization for Research and Treatment of Cancer Quality of Life C30 questionnaire domains. Additional domains were used to cluster other symptoms mentioned: menopausal, sex-related, body alteration, and eye-related. The following clusters were the most frequently presented: sex-related (14 symptoms), pain (9 symptoms), insomnia (5 symptoms), and menopausal (5 symptoms). CONCLUSION: The target group reported a variety of symptoms related to aromatase inhibitors. No tools are currently available to measure all the symptoms reported, indicating a need to revise the tools to acknowledge additional symptoms. Prospective studies are needed to investigate the prevalence of aromatase inhibitor-related symptoms in women with breast cancer. IMPLICATION FOR NURSING PRACTICE: Identification of patient-reported clinically relevant symptoms can enable targeted symptom assessment and management strategies for women with breast cancer undergoing aromatase inhibitor treatment.

Symptom Patterns in Young Adults with Cancer: An App-Based Study.

OBJECTIVES: To investigate symptom patterns in young adults with cancer using a smartphone-based app. The authors sought to explore symptom frequency and severity, cluster patients based on their symptom severity, investigate the co-occurrence of severe symptoms, and explore the relationship between symptoms and activities. DATA SOURCES: Data were collected, using a mobile app, from 161 young adults with cancer (mean age 25.5 years, 75% female, 59% with solid cancer). Symptom frequency/severity was investigated with descriptive statistics. K-means clustering technique was used to cluster patients based on the average symptom severity. Co-occurrence of severe symptoms was investigated with the association rule technique. The relationship between symptom severity and likelihood of performing a physical/social activity was explored with mixed-effects logistic regression. CONCLUSION: The most frequently reported symptom was mood disturbance, followed by fatigue, which was also the most severe one. Two clusters of patients were identified, experiencing higher and lower severity for all symptoms. Severe appetite disturbances were frequently reported together with severe lack of energy and nausea. Severe lack of energy, either alone or together with mood disturbance, was often reported together with severe fatigue. Higher mood disturbance was associated with lower probability of performing physical and social activities. This study provides new insights into the symptom experience of young adults with cancer. IMPLICATIONS FOR NURSING PRACTICE: Using a symptoms-tracking app may be a valid strategy for healthcare professionals, nurses, and researchers to support patients in symptom monitoring and, consequently, to identify and implement tailored symptom-management strategies.

Research involvement and engagement of adolescent and young adults in a cancer trajectory: a 5-year experience from a patient support facility at a university hospital.

BACKGROUND: The purpose of this case study is to describe how a vulnerable group of patients can be included in research. The activities, challenges, lessons learned, and reflections on the importance of patient involvement in research for 5 years (2016-2021) at the adolescent and young adult (AYA) cancer support facility, Kræftværket, are reported. MAIN BODY: A patient panel at Kræftværket, the Youth Panel has multiple aims, one of which is the ability to perform patient involvement in research, with the goal of achieving research of high quality. We here describe how Patient and Public involvement (PPI) can be customized to AYAs in a cancer trajectory, who face many challenges, including those in the physical, psychological, and social domains. During 2016-2021, Youth Panel meetings were planned every third month but interrupted during the COVID-19 pandemic. With a flexible structure and a dynamic panel including 10-15 varying AYAs in a cancer trajectory, engagement and involvement have been maintained. Eight research topics were investigated, seven of which were discussed and confirmed to be important by the Youth Panel. Out of eight topics, three were raised by patients, and five by researchers. One was not discussed due to COVID-19. Some of the challenges we have experienced were related to the flexible meeting structure and the differing expectations and priorities as well as the impact of COVID-19. However, we experienced that patient involvement is possible in the field of AYA oncology if a trusting environment is created. A key finding in our case study was, that without a national Danish PPI program and no defined international standard for PPI in AYA cancer research yet, we were able to give patients the possibility to give input to researchers on topics where research is missing. CONCLUSION: Here, we demonstrate how patient involvement in research has been performed at an AYA cancer facility, Kræftværket, during a 5-year period. We encourage others to perform patient-involving research, even in challenging populations. Ideally this must follow international standards for PPI in AYA cancer research when such exist to improve research with crucial insight from patients.

In this paper, we describe patient involvement in research at Kræftværket, a youth support center and social organization for AYAs in a cancer trajectory. The center is located at The University Hospital Rigshospitalet in Copenhagen, Denmark. Youth panel meetings are Kræftværkets' most central patient involvement activity, and one of its aims is to facilitate high-quality patient-initiated research. AYA cancer patients are a vulnerable group facing huge psycho-social challenges and symptoms that make normal functioning difficult. Therefore, the youth panel is designed to be flexible in its structure, so participants do not have to commit themselves as permanent members. The youth panel meets four times a year, and during the period 2016­2021, it has been involved in eight research topics. Challenges include the flexible meeting structure, different expectations, and priorities as well as the impact of COVID-19. However, patient involvement has been possible because of a trusting environment with strong nurse-led support for the participants. We hope to encourage others to argue for and carry out meaningful patient-involving research to improve tomorrow's quality of AYA cancer care.

A multi-method approach to selecting PRO-CTCAE symptoms for patient-reported outcome in women with endometrial or ovarian cancer undergoing chemotherapy.

BACKGROUND: Women with endometrial or ovarian cancer experience a variety of symptoms during chemotherapy. Patient-Reported outcomes (PROs) can provide insight into the symptoms they experience. A PRO tool tailored to this patient population can help accurately monitor adverse events and manage symptoms. The objective of this study was to identify items in the National Cancer Institute's measurement system Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) appropriate for use in a PRO tool for a population of women with endometrial or ovarian cancer undergoing treatment with taxanes (paclitaxel or docetaxel) in combination with carboplatin. METHODS: A two-phase, sequential multi-methods approach was applied. In phase one, a comprehensive literature search was done to map the toxicity of the applied chemotherapeutics and phase III clinical studies. Phase two, which comprised selecting the PRO-CTCAE items, included discussions with and feedback from a patient advisory board, an additional literature search, and focus group interviews with senior oncologists and specialized oncology nurses. A national expert panel facilitated both phases in terms of carefully select items from the PRO-CTCAE library. RESULTS: Phase one identified 18 symptoms and phase two, three additional ones, leading to the inclusion of 21 PRO-CTCAE symptoms in the final PRO tool. Since PRO-CTCAE also contains one to three sub-questions on the frequency, severity, and interference with daily activities of symptoms, there were 44 potential items. CONCLUSIONS: This study describes taking a multi-method approach to selecting items from the PRO-CTCAE library for use in a population of women with endometrial or ovarian cancer undergoing chemotherapy. By systematically combining diverse approaches, we carefully selected 21 clinically relevant symptoms covered by 44 items in the PRO-CTCAE library. Future studies should investigate the psychometric properties of this PRO tool for women with endometrial or ovarian cancer.

Treatment Patterns and Efficacy of Chemotherapy After Pembrolizumab in Advanced Urothelial Cancer-a Real-World Study in the pre-Antibody-Drug Conjugate Era.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been established as a routine treatment in patients with metastatic urothelial cancer (mUC). However, there has been no standard of care after progression on ICIs. We investigated real-world treatment patterns and efficacy of chemotherapy (CHT) after pembrolizumab, in the era before introduction of maintenance avelumab and antibody-drug conjugates (ADC). PATIENTS AND METHODS: An observational, retrospective study was conducted at twelve Nordic centers. Patients with mUC were treated according to investigator´s choice of CHT after pembrolizumab. Primary endpoint was overall response (ORR) and disease control rate (DCR); secondary endpoints were progression-free (PFS) and overall survival (OS). RESULTS: In total, 102 patients were included whereof 23 patients received CHT after pembrolizumab as second line treatment (subcohort A) and 79 patients in third line (subcohort B). Platinum-gemcitabine combinations were the most common regimens in subcohort A, and vinflunine in subcohort B. The ORR and DCR were 36% and 47%, respectively. Presence of liver metastases was independently associated with lower ORR and DCR. The PFS and OS were 3.3 months and 7.7 months, respectively. Eastern Cooperative Oncology Group Performance Status (ECOG PS) and number of previous cycles of pembrolizumab were found to be independent prognostic factors associated with OS. CONCLUSION: In a real-world setting, CHT showed clinically meaningful response rates and survival in mUC patients after progression with pembrolizumab. Clinical benefit may primarily be achieved in patients with favorable ECOG PS, in patients treated with > 6 cycles pembrolizumab as well as in patients without presence of liver metastases.