Is cancer associated with frailty? Results from a longitudinal study of old Danish twins.

BACKGROUND: While age is an important risk factor for both cancer and frailty, it is unclear whether cancer itself increases the risk of frailty. We aimed to assess the association between cancer and frailty in a longitudinal cohort of older Danish twins, taking familial effect into account. METHODS: Using the Danish Cancer Registry, cancer cases were identified among participants aged 70 and over in the Longitudinal Study of Aging Danish Twins (LSADT). Frailty was evaluated over 10 years of follow-up using the frailty index (FI) and defined as FI > 0.21. Stratified Cox regressions were performed on discordant twin pairs (pairs where one twin had incident cancer and the other was cancer-free), and on all LSADT individual twins (twin pairs and singletons) with no history of cancer. RESULTS: Among the 72 discordant pairs (n=144, median age at inclusion=75) included in the study, the median FI at inclusion was 0.08 for both cancer twins and cancer-free co-twins. From the stratified Cox regression, twins with cancer had an increased hazard of developing frailty (HR=3.67, 95%CI=1.02,13.14) compared to their cancer-free co-twins. The analyses on individual twins (n=4,027) provided similar results, showing an increased hazard of frailty in individuals with cancer (HR=2.57, 95%CI= 1.77,3.74) compared to those without cancer. CONCLUSIONS: We showed a higher risk of becoming frail following a cancer diagnosis in both discordant twin pairs and individual twins. These findings support the importance of monitoring of frailty in older adults with cancer through geriatric assessments and implementation of frailty interventions.

Association between Geriatric 8 frailty and health-related quality of life in older patients with cancer (PROGNOSIS-G8): a Danish single-centre, prospective cohort study.

BACKGROUND: Health-related quality of life (HRQoL) is highly valued among older adults with cancer. The Geriatric 8 screening tool identifies individuals with frailty, but its association with HRQoL remains sparsely investigated. Herein, we evaluate whether Geriatric 8 frailty is associated with short-term and long-term HRQoL in older patients with cancer. METHODS: In this Danish single-centre, prospective cohort study, patients aged 70 years and older, referred to oncological assessment for solid cancers, were screened with the Geriatric 8. Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Core 30 (QLQ-C30) and Elderly 14 (ELD14) questionnaires at baseline, 3 months, 6 months, 9 months, and 12 months. Patient characteristics were obtained from medical records. Differences in mean global health status and QoL (GHS), measured using the two seven-point Likert scale questions from the EORTC QLQ-C30 regarding overall health and QoL during the past week, between patients with frailty (defined as a Geriatric 8 score of ≤14) and without frailty within 12 months were the primary outcome. Secondary outcomes were differences in the mean EORTC Summary Score comprised of all questions from the QLQ-C30 except for those included in the GHS and a question concerning financial difficulties, and five functional (physical, role, and social functioning, maintaining purpose, and family support from the EORTC QLQ-C30 and the EORTC-QLQ-ELD14), and five symptom scales (fatigue, pain, mobility, future worries, and burden of illness from the EORTC-QLQ-C30 and the EORTC-QLQ-ELD14). Analyses were done using linear mixed models. All primary and secondary outcomes were adjusted for gender, treatment intent, and cancer type and the primary outcome was also assessed by means of a responder analysis. FINDINGS: Between June 1, 2020 and Oct 15, 2021, 1398 eligible patients were screened with the Geriatric 8 (908 [65%] with frailty and 490 [35%] without frailty) and provided medical record data. Of these patients, 707 (51%) also provided HRQoL data (437 [62%] with frailty and 270 [38%] without frailty). When adjusted, patients with frailty had poorer GHS (-15·1, 95% CI -18·5 to -11·6; p<0·0001) at baseline and throughout follow-up (3 months -7·4, -11·0 to -3·7, p=0·0001; 6 months -11·7, -15·5 to -7·9, p<0·0001; 9 months -10·4, -14·3 to -6·5, p<0·0001; 12 months -10·4, -14·6 to -6·2, p<0·0001) compared to patients without frailty. Adjusted summary scores were also poorer for patients with frailty (-9·9, 95% CI -12·1 to -7·6; p<0·0001) compared to patients without frailty at baseline and throughout follow-up (3 months -8·2, -10·5 to -5·8, p=0·0001; 6 months -9·0, -11·4 to -6·6, p<0·0001; 9 months -9·2, -11·7 to -6·8, p<0·0001; 12 months -8·9, -11·5 to -6·3, p<0·0001). Patients with frailty had significantly worse physical and role functioning, mobility, and fatigue outcomes, with no differences in family support within 12 months, at all timepoints. INTERPRETATION: Older patients with cancer and frailty have significantly poorer HRQoL than those without frailty within the 12 months following an oncology referral. Thus, by identifying and treating frailty, we can ultimately improve patient HRQoL. FUNDING: The Danish Cancer Society, Academy of Geriatric Cancer Research (AgeCare), Odense University Hospital, University of Southern Denmark, Dagmar Marshalls Fond, and Agnes and Poul Friis Fond.

Effect of comprehensive geriatric assessment on hospitalizations in older adults with frailty initiating curatively intended oncologic treatment: The PROGNOSIS-RCT study.

INTRODUCTION: Frailty constitutes a risk for unplanned hospitalizations in older adults with cancer. This study examines whether comprehensive geriatric assessment (CGA) as an add-on to standard oncologic care can prevent unplanned hospitalizations in older adults with frailty and cancer who initiate curative oncological treatment. MATERIALS AND METHODS: This randomized controlled trial included older adults aged ≥70 with frailty (Geriatric 8 [G8] ≤14), and solid cancers who initiated curative oncological treatment. Participants were randomized 1:1 to either standard oncologic care (control) or standard oncologic care supplemented with CGA-guided interventions (intervention). Baseline characteristics were retrieved prior to randomization. The primary endpoint, the between-group rate ratio of unplanned hospitalizations within six months of treatment initiation, was analyzed using negative binominal regression. Analyses were performed using an intention-to-treat approach, followed by per-protocol analysis, including participants receiving CGA within 30 days of randomization, and preplanned subgroup analyses based on treatment modality and Geriatric 8 screening. Secondary endpoints included acute hospital contacts, treatment adherence, and toxicity. RESULTS: From November 1, 2020 to May 31, 2023, 173 participants were enrolled. Median age was 75 (interquartile range 72-79), 51.5% were female, 58% had a G8 score > 12, and 84% had Eastern Cooperative Oncology Group performance status 0-1. The most common cancer sites were lung (23%), upper gastrointestinal (15%), and breast (13%). The rate (per person-years) of unplanned hospitalization was 1.32 in the intervention group and 1.81 in the control group, with a between-group rate ratio of 0.74 (95% confidence interval [CI] 0.45-1.23, P = 0.25) favoring the intervention. The between-group rate ratio increased in the per-protocol analysis (0.64 [95% CI 0.37-1.10, P = 0.10]). Similarly, no significant between group differences were found in treatment adherence, rate of acute hospital contacts, or toxicity. DISCUSSION: In this study, CGA did not significantly reduce the rate of unplanned hospitalizations. Furthermore, no between-group differences were found in treatment adherence, toxicity lead hospitalizations, or treatment completion in older adults with cancer and frailty. However, per-protocol analysis suggests that increasing adherence to CGA may improve the outcome. Larger studies ensuring higher CGA adherence are warranted to confirm our findings.

Association of cancer with functional decline at old age: a longitudinal study in Danish twins.

INTRODUCTION: There is evidence that older adults with cancer have a higher risk of functional decline than cancer-free older adults. However, few studies are longitudinal, and none are twin studies. Thus, we aimed to investigate the relationship between cancer and functional decline in older adult (aged 70+ years) twins. MATERIALS AND METHODS: Cancer cases in the Longitudinal Study of Aging Danish Twins were identified through the Danish Cancer Registry. Functional status was assessed using hand grip strength (6 years follow-up), and self-reported questions on mobility (10 years follow-up), and cut-offs were defined to assess functional decline. Cox regression models were performed for all the individual twins. In addition, we extended the analysis to discordant twin pairs (twin pairs with one having cancer and the other being cancer-free), to control to a certain extent for (unmeasured) shared confounders (genetic and environmental factors). RESULTS: The analysis based on individual twins showed that individual twins with cancer are at increased hazard of worsening hand grip strength (hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.04, 1.80) than cancer-free twins. Among the discordant twin pairs, twins with cancer had a higher hazard of worsening hand grip strength (HR 3.50, 95% CI 1.15, 10.63) than cancer-free cotwins. In contrast, there was no evidence of a difference between the hazard of experiencing mobility decline for twins with cancer compared with cancer-free twins, in both individual twins and discordant twin pairs analyses. DISCUSSION: Cancer was associated with hand grip strength functional decline in old individual twins and discordant pairs. Our results strengthen the importance of comprehensive geriatric assessment in older adults with cancer, as well as the importance of routine assessment of functional status. Promoting physical activity through exercise training programmes could enable the prevention of functional decline in older adults with cancer.

Geriatric screening and frailty intervention in older patients with cancer.

Frailty in older patients with cancer increases the risk of treatment related toxicity, mortality, physical decline, and quality of life. This review summarises various screening tools. Screening tools identifying frailty serve multiple purposes, providing awareness of health issues impacting oncologic treatment and prognosis and facilitating the delivery of a Comprehensive Geriatric Assessment (CGA). CGA is an overall health assessment and treatment targeting frailty. Providing CGA to older patients with cancer reduces the risk of toxicity and functional decline, increases treatment completion, and prevents loss of quality of life.

Effects of comprehensive geriatric assessment-guided interventions on physical performance and quality of life in older patients with advanced cancer: A randomized controlled trial (PROGNOSIS-RCT).

INTRODUCTION: Older patients with frailty starting oncological treatment are at higher risk of experiencing declining physical performance, loss of independence, and quality of life (QoL). This study examines whether comprehensive geriatric assessment (CGA)-guided interventions added to standard oncological care can prevent declining physical performance and QoL in older patients with frailty initiating palliative treatment. MATERIALS AND METHODS: Patients aged ≥70 years, with a Geriatric-8 score of ≤14, initiating palliative oncological treatment were enrolled in an open label randomized controlled trial and randomized 1:1 to receive either CGA-guided interventions in addition to oncological standard care or oncological care alone. Baseline characteristics, physical performance measures, and QoL questionnaires were retrieved before group allocation. CGA was performed using a fixed set of domains and validated tests by a geriatrician-led team. The primary endpoint, physical performance, was measured by the 30-s chair stand test (30s-CST) at three months. Additional outcomes included 30s-CST at six months, handgrip strength test, and QoL. Outcomes were analyzed using linear mixed regression models. The trial was registered at clinicaltrials.org (NCT04686851). RESULTS: From November 1, 2020 to May 31, 2022, 181 patients were included; 88 in the interventional arm and 93 in the control arm. Median age was 77 (interquartile range [IQR] 73-81) years, 69% were male, median Geriatric-8 score was 12 (IQR 10-13), 69% had a Performance Status of 0-1, and the median 30s-CST was 9 (IQR 5-11) repetitions. The between-group difference in 30s-CST at three months was 0.67 (95%CI: -0.94 - 2.29) and 1.57 (95%CI: -0.20 - 3.34) at six months, which were not statistically significant. Subgroup analysis including participants with a baseline Geriatric-8 of 12-14 found borderline significant between-group differences in 30s-CST scores at three and six months of 2.04 (95% confidence interval [CI]: -0.07 - 4.2, P = 0.06) and 2.25 (95%CI: 0.01-4.5, P = 0.05), respectively. No within-group or between-group differences in the summary score or the Elderly Functional Index score (measuring QoL) were found. DISCUSSION: This study did not find significant between-group differences in the 30s-CST in older patients receiving palliative care. However, a tendency towards improved physical performance was seen in the least frail. These patients may represent a target group wherein CGA interventions provide particular benefit.

The Pattern of Metastatic Breast Cancer: A Prospective Head-to-Head Comparison of [18F]FDG-PET/CT and CE-CT.

The study aimed to compare the metastatic pattern of breast cancer and the intermodality proportion of agreement between [18F]FDG-PET/CT and CE-CT. Women with metastatic breast cancer (MBC) were enrolled prospectively and underwent a combined [18F]FDG-PET/CT and CE-CT scan to diagnose MBC. Experienced nuclear medicine and radiology physicians evaluated the scans blinded to the opposite scan results. Descriptive statistics were applied, and the intermodality proportion of agreement was used to compare [18F]FDG-PET/CT and CE-CT. In total, 76 women with verified MBC were enrolled in the study. The reported number of site-specific metastases for [18F]FDG-PET/CT vs. CE-CT was 53 (69.7%) vs. 44 (57.9%) for bone lesions, 31 (40.8%) vs. 43 (56.6%) for lung lesions, and 16 (21.1%) vs. 23 (30.3%) for liver lesions, respectively. The proportion of agreement between imaging modalities was 76.3% (95% CI 65.2-85.3) for bone lesions; 82.9% (95% CI 72.5-90.6) for liver lesions; 57.9% (95% CI 46.0-69.1) for lung lesions; and 59.2% (95% CI 47.3-70.4) for lymph nodes. In conclusion, bone and distant lymph node metastases were reported more often by [18F]FDG-PET/CT than CE-CT, while liver and lung metastases were reported more often by CE-CT than [18F]FDG-PET/CT. Agreement between scans was highest for bone and liver lesions and lowest for lymph node metastases.

Obesity and Risk of Recurrence in Patients With Breast Cancer Treated With Aromatase Inhibitors.

Importance: Clinical studies confirm that obesity is a risk factor for recurrence in postmenopausal women with hormone receptor-positive (HR+) breast cancer. Evidence suggests that women with obesity do not obtain similar protection from aromatase inhibitors as women with healthy weight. Objective: To examine the associations of body mass index (BMI) with recurrence. Design, Setting, and Participants: The cohort study was conducted using data from the Danish Breast Cancer Group and enrolled postmenopausal women diagnosed with stage I to III HR+ breast cancer from 1998 through 2016. Data analysis was conducted from November 2022 to April 2023. Exposures: BMI was classified as (1) healthy weight (18.5-24.9), (2) overweight (25.0-29.9), (3) obesity (30.0-34.9), and (4) severe obesity (≥35.0) using the World Health Organization guidelines. Healthy weight was considered the reference group in statistical analyses. Main Outcomes and Measures: Follow-up began 6 months after breast cancer surgery and continued until the first event of recurrence, contralateral breast cancer, new primary malignant neoplasm, death, emigration, end of clinical follow-up at 10 years, or September 25, 2018. Cox regression was used to estimate crude and adjusted hazard ratios with 95% CIs, adjusting for patient, tumor, and treatment characteristics. Results: A total of 13 230 patients (median [IQR] age at diagnosis, 64.4 [58.6-70.2] years) with information on BMI were enrolled. There were 1587 recurrences with a median (IQR) potential estimated follow-up of 6.2 (3.6-8.5) years. Multivariable analyses revealed increased recurrence hazards associated with obesity (adjusted hazard ratio, 1.18 [95% CI, 1.01-1.37]) and severe obesity (adjusted hazard ratio, 1.32 [95% CI, 1.08-1.62]) vs patients with healthy weight. Patients with overweight had a greater risk, but the results were not statistically significant (adjusted hazard ratio, 1.10 [95% CI, 0.97-1.24]). Conclusions and Relevance: In this study, obesity was associated with an increased risk of breast cancer recurrence among postmenopausal patients with HR+ early-stage breast cancer treated with aromatase inhibitors. Physicians should be aware of the significance of obesity on breast cancer outcomes to secure optimal treatment benefit in all patients.

2-[18F]FDG-PET/CT is a better predictor of survival than conventional CT: a prospective study of response monitoring in metastatic breast cancer.

This study aimed to compare CE-CT and 2-[18F]FDG-PET/CT for response monitoring metastatic breast cancer (MBC). The primary objective was to predict progression-free and disease-specific survival for responders vs. non-responders on CE-CT and 2-[18F]FDG-PET/CT. The secondary objective was to assess agreement between response categorization for the two modalities. Treatment response in women with MBC was monitored prospectively by simultaneous CE-CT and 2-[18F]FDG-PET/CT, allowing participants to serve as their own controls. The standardized response evaluation criteria in solid tumors (RECIST 1.1) and PET response criteria in solid tumors (PERCIST) were used for response categorization. For prediction of progression-free and disease-specific survival, treatment response was dichotomized into responders (partial and complete response) and non-responders (stable and progressive disease) at the first follow-up scan. Progression-free survival was defined as the time from baseline until disease progression or death from any cause. Disease-specific survival was defined as the time from baseline until breast cancer-specific death. Agreement between response categorization for both modalities was analyzed for all response categories and responders vs. non-responders. At the first follow-up, tumor response was reported more often by 2-[18F]FDG-PET/CT than CE-CT, with only fair agreement on response categorization between the two modalities (weighted Kappa 0.28). Two-year progression-free survival for responders vs. non-responders by CE-CT was 54.2% vs. 46.0%, compared with 59.1% vs. 14.3% by 2-[18F]FDG-PET/CT. Correspondingly, 2-year disease-specific survival were 83.3% vs. 77.8% for CE-CT and 84.6% vs. 61.9% for 2-[18F]FDG-PET/CT. Tumor response on 2-[18F]FDG-PET/CT was significantly associated with progression-free (HR: 3.49, P < 0.001) and disease-specific survival (HR 2.35, P = 0.008), while no association was found for tumor response on CE-CT. In conclusion, 2-[18F]FDG-PET/CT appears a better predictor of progression-free and disease-specific survival than CE-CT when used to monitor metastatic breast cancer. In addition, we found low concordance between response categorization between the two modalities. TRIAL REGISTRATION: Clinical. TRIALS: gov. NCT03358589. Registered 30/11/2017-Retrospectively registered, http://www. CLINICALTRIALS: gov.

Breast cancer, breast cancer-directed radiation therapy and risk of hypothyroidism: A systematic review and meta-analysis.

OBJECTIVE: Breast cancer and breast cancer-directed radiation therapy (RT) may increase the risk of late effects, such as hypothyroidism. We conducted a systematic review and meta-analysis to investigate the association between breast cancer, RT, and risk of hypothyroidism in breast cancer survivors. METHODS: Through February 2022, we searched PubMed, EMBASE, and references of relevant articles, to identify papers on breast cancer and breast cancer-directed RT and subsequent risk of hypothyroidism. Articles were screened by title and abstract and reviewed for eligibility. We used a pre-formed data extraction sheet and identified key design elements that could potentially introduce bias. The main outcome was the confounder-adjusted relative risk (RR) of hypothyroidism in breast cancer survivors versus women without breast cancer, and in breast cancer survivors according to the receipt of RT to the supraclavicular lymph nodes. We used a random-effects model to calculate pooled RRs and associated 95% confidence intervals (95% CI). RESULTS: From 951 papers screened by title and abstract, 34 full-text papers were reviewed for eligibility. We included 20 studies published between 1985 and 2021-19 were cohort studies. Compared with women without breast cancer, the pooled RR of hypothyroidism in breast cancer survivors was 1.48 (95% CI: 1.17, 1.87), with highest risk associated with RT to the supraclavicular region (RR = 1.69, 95% CI: 1.16, 2.46). The most important limitations of the studies were small sample size yielding estimates with low precision, and lack of data on potential confounders. CONCLUSION: Breast cancer and radiation therapy to the supraclavicular lymph nodes is associated with an increased risk of hypothyroidism.

Response Monitoring in Metastatic Breast Cancer: A Prospective Study Comparing 18F-FDG PET/CT with Conventional CT.

This study aimed to compare contrast-enhanced CT (CE-CT) and 18F-FDG PET/CT for response monitoring in metastatic breast cancer using the standardized response evaluation criteria RECIST 1.1 and PERCIST. The objective was to examine whether progressive disease was detected systematically earlier by one of the modalities. Methods: Women with biopsy-verified metastatic breast cancer were enrolled prospectively and monitored using combined CE-CT and 18F-FDG PET/CT every 9-12 wk to evaluate response to first-line treatment. CE-CT scans and RECIST 1.1 were used for clinical decision-making without accessing the 18F-FDG PET/CT scans. At study completion, 18F-FDG PET/CT scans were unmasked and assessed according to PERCIST. Visual assessment was used if response criteria could not be applied. The modality-specific time to progression was defined as the time from the baseline scan until the first scan demonstrating progression. Paired comparative analyses for CE-CT versus 18F-FDG PET/CT were applied, and the primary endpoint was earlier detection of progression by one modality. Secondary endpoints were time to detection of progression, response categorization, visualization of changes in response over time, and measurable disease according to RECIST and PERCIST. Results: In total, 87 women were evaluable, with a median of 6 (1-11) follow-up scans. Progression was detected first by 18F-FDG PET/CT in 43 (49.4%) of 87 patients and first by CE-CT in 1 (1.15%) of 87 patients (P < 0.0001). Excluding patients without progression (n = 32), progression was seen first on 18F-FDG PET/CT in 78.2% (43/55) of patients. The median time from detection of progression by 18F-FDG PET/CT to that of CE-CT was 6 mo (95% CI, 4.3-6.4 mo). At baseline, 76 (87.4%) of 87 patients had measurable disease according to PERCIST and 51 (58.6%) of 87 patients had measurable disease according to RECIST 1.1. Moreover, 18F-FDG PET/CT provided improved visualization of changes in response over time, as seen in the graphical abstract. Conclusion: Disease progression was detected earlier by 18F-FDG PET/CT than by CE-CT in most patients, with a potentially clinically relevant median 6-mo delay for CE-CT. More patients had measurable disease according to PERCIST than according to RECIST 1.1. The magnitude of the final benefit for patients is a perspective for future research.

DPYD genotyping and dihydropyrimidine dehydrogenase (DPD) phenotyping in clinical oncology. A clinically focused minireview.

BACKGROUND: In clinical oncology, systemic 5-fluorouracil (5-FU) and its oral pro-drugs are used to treat a broad group of solid tumours. Patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency are at elevated risk of toxicity if treated with standard doses of 5-FU. DPYD genotyping and measurements of plasma uracil concentration (DPD phenotyping) can be applied as tests for DPD deficiency. In April 2020, the European Medicines Agency recommended pre-treatment DPD testing to reduce the risk of 5-FU-related toxicity. OBJECTIVES: The objective of this study is to present the current evidence for DPD testing in routine oncological practice. METHODS: Two systematic literature searches were performed following the PRISMA guidelines. We identified studies examining the possible benefit of DPYD genotyping or DPD phenotyping on the toxicity risk. FINDINGS: Nine and 12 studies met the criteria for using DPYD genotyping and DPD phenotyping, respectively. CONCLUSIONS: The evidence supporting either DPYD genotyping or DPD phenotyping as pre-treatment tests to reduce 5-FU toxicity is poor. Further evidence is still needed to fully understand and guide clinicians to dose by DPD activity.

Cancer-Related Reductions in Survival: Extent and Duration Evaluated Using a Large Cohort Study of Twins, 1943-2011.

BACKGROUND: The time during which there is an increased risk of death for cancer survivors was evaluated in a large twin study, which allows for matching on shared components such as age, genes, and socioeconomic factors in childhood. METHODS: By use of data from Danish registers, time to death from initial cancer was studied prospectively in twins in two different settings. The twins were diagnosed with at least one cancer in the period 1943 to 2011. Setting I included 5,680 same-sex twin pairs aged 6 and over, while Setting II included 3,218 twin individuals from age 70 and over. The study provides comparisons within twin pairs and across birth cohorts, age at diagnoses, and time at diagnosis. RESULTS: In 2001 to 2011, the 5-year mortality risk for a twin surviving cancer after the age of 70 was twofold that of the co-twin, regardless of sex and zygosity, and it was 1.5-fold if the twin survived the initial 9 months. After 5 to 6 years, the mortality risk corresponded to that of the co-twin. In previous decades, the excess hazard risk was considerably higher for both older and younger cohorts. There were no indications of change in relative survival across old birth cohorts. CONCLUSIONS: This large twin study suggested that for a cancer-treatment survivor diagnosed at age 70 or later, the additional mortality risk was largely absent 5 years later, by which time the survival relative to the co-twin was 60%. IMPACT: Elevated mortality risk after cancer is offset after 5 to 6 years.

Predictive value of geriatric oncology screening and geriatric assessment of older patients with cancer: A randomized clinical trial protocol (PROGNOSIS-RCT).

INTRODUCTION: Comprehensive geriatric assessment (CGA) has been shown to reduce frailty in older patients in general. In older patients with cancer, frailty affects quality of life (QoL), physical function, and survival. However, few studies have examined the effect of CGA as an additional intervention to antineoplastic treatment. This protocol presents a randomized controlled trial, which aims to evaluate the effects of CGA-based interventions in older patients with cancer and Geriatric 8 (G8) identified frailty. MATERIALS AND METHODS: This randomized controlled trial will include patients, age 70+ years, with solid malignancies and G8 frailty (G8 ≤ 14). Patients will be separated into two groups, with different primary endpoints, depending on palliative or curative antineoplastic treatment initiation, and subsequently randomized 1:1 to either CGA with corresponding interventions or standard of care, along with standardized antineoplastic treatment. A geriatrician led CGA with corresponding interventions and clinical follow-up will be conducted within one month of antineoplastic treatment initiation. The interdisciplinary CGA will cover multiple geriatric domains and employ a standard set of validated assessment tools. Primary endpoints will be physical decline measured with the 30-s Chair-Stand-Test at three months (palliative setting) and unplanned hospital admissions at six months (curative setting). Additional outcomes include QoL, treatment toxicity and adherence, occurrence of polypharmacy, potential drug interactions, potential inappropriate medications, and survival. The primary outcomes will be analyzed using a mixed model regression analysis (30-s chair stand test) and linear regression models (unplanned hospitalizations), with an intention to treat approach. Power calculations reveal the need to enroll 134 (palliative) and 188 (curative) patients. DISCUSSION: The present study will examine whether CGA, as an additional intervention to antineoplastic treatment, can improve endpoints valued by older patients with cancer. Inclusion began November 2020 and is ongoing, with 37 and 29 patients recruited April 15th, 2021. Registration:NCT04686851.

[Challenges in cancer treatment for the elderly].

About half of all Danish cancer patients are 70 years or older at diagnosis. The incidence is expected to increase further over the coming years because of an increasing longevity. Therefore, this review recommends that the Danish health care system develops and implement models to ensure optimal care for older adults with cancer. We are still in need of knowledge about the optimal treatment, rehabilitation, palliation and care for older adults with cancer. We encourage the Danish health authorities to formulate a national strategy for this area.

Benefits and harms of implementing [18F]FDG-PET/CT for diagnosing recurrent breast cancer: a prospective clinical study.

BACKGROUND: [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) has been implemented sporadically in hospital settings as the standard of care examination for recurrent breast cancer. We aimed to explore the clinical impact of implementing [18F]FDG-PET/CT for patients with clinically suspected recurrent breast cancer and validate the diagnostic accuracy. METHODS: Women with suspected distant recurrent breast cancer were prospectively enrolled in the study between September 2017 and August 2019. [18F]FDG-PET/CT was performed, and the appearance of incidental benign and malignant findings was registered. Additional examinations, complications, and the final diagnosis were registered to reflect the clinical consequence of such findings. The diagnostic accuracy of [18F]FDG-PET/CT as a stand-alone examination was analyzed. Biopsy and follow-up were used as a reference standard. RESULTS: [18F]FDG-PET/CT reported breast cancer metastases in 72 of 225 women (32.0%), and metastases were verified by biopsy in 52 (52/225, 23.1%). Prior probability and posterior probability of a positive test for suspected metastatic cancer and incidental malignancies were 27%/85% and 4%/20%, respectively. Suspected malignant incidental findings were reported in 46 patients (46/225, 20.4%), leading to further examinations and final detection of nine synchronous cancers (9/225, 4.0%). These cancers originated from the lung, thyroid, skin, pancreas, peritoneum, breast, kidney, one was malignant melanoma, and one was hematological cancer. False-positive incidental malignant findings were examined in 37/225 patients (16.4%), mainly in the colon (n = 12) and thyroid gland (n = 12). Ten incidental findings suspicious for benign disease were suggested by [18F]FDG-PET/CT, and further examinations resulted in the detection of three benign conditions requiring treatment. Sensitivity, specificity, and AUC-ROC for diagnosing distant metastases were 1.00 (0.93-1.0), 0.88 (0.82-0.92), and 0.98 (95% CI 0.97-0.99), respectively. CONCLUSION: [18F]FDG-PET/CT provided a high posterior probability of positive test, and a negative test was able to rule out distant metastases in women with clinically suspected recurrent breast cancer. One-fifth of patients examined for incidental findings detected on [18F]FDG-PET/CT were diagnosed with clinically relevant conditions. Further examinations of false-positive incidental findings in one of six women should be weighed against the high accuracy for diagnosing metastatic breast cancer. Trial registration Clinical.Trials.gov. NCT03358589. Registered 30 November 2017-Retrospectively registered, http://www.ClinicalTrials.gov.

Immediate evaluation of global longitudinal strain at initiation of trastuzumab treatment in breast cancer patients.

BACKGROUND: Global longitudinal strain (GLS) is recommended to detect subclinical changes preceding reduced left ventricular ejection fraction (LVEF) in trastuzumab related cardiotoxicity. Since the possibility to detect signs of acute myocardial deterioration at treatment initiation is not clarified, the objective of this study was to assess changes in GLS and biomarkers within the first 2 weeks of trastuzumab treatment. METHODS: In a prospective cohort study, 45 patients with non-metastatic breast cancer (age 54, LVEF 62.8%, GLS -19.9%, 40% hypertension) scheduled for trastuzumab treatment were included. Echocardiography and measurement of troponin and NT-proBrain-Natriuretic-Peptide were conducted before initiation of trastuzumab, at days 3, 7, and 14 and after 3, 6, and 9 months. RESULTS: A significant deterioration in LVEF from 62.8% (SD±3.6) to 58.4% (SD±4.1) (p < 0.0001), GLS from -19.9 (SD±2.1) to -18.1 (SD±2.5) (p = 0.004), s' (p < 0.0001), e' septal (p = 0.008), and s' RV (p < 0.0001) occurred at 9 months and was preceded by significant changes in these parameters within the first 14 days. After 14 days, 12 patients (27%) had a ≥10% deterioration in GLS, which was associated with significantly lower LVEF at 55.2% (SD±4.1) at 9 months compared to patients with < 10% early deterioration in GLS (LVEF = 59.5% (SD±3.5) (p = 0.001)). No difference in plasma concentrations of biomarkers was observed between the two groups. CONCLUSION: In this study deteriorations in key echocardiographic parameters within normal limits were detected during the first 2 weeks of trastuzumab treatment, and an early ≥10% deterioration in GLS was associated with a lower LVEF at 9 months.

Predictive Value of Geriatric Oncology Screening and Geriatric Assessment in Older Patients with Solid Cancers: Protocol for a Danish prospective cohort study (PROGNOSIS-G8).

INTRODUCTION: Older patients with cancer constitute a heterogeneous group with varying degrees of frailty; therefore, geriatric assessment with initial geriatric oncology screening is recommended. The Geriatric 8 (G8) and the modified Geriatric 8 (mG8) are promising screening tools with high accuracy and an association with survival. However, evidence is sparse regarding patient-centered outcomes. This protocol describes a study, which aims to address the predictive and prognostic value of the G8 and mG8, with quality of life (QoL) as the primary outcome. MATERIALS AND METHODS: In this single-center prospective cohort study, patients, age ≥70 years with solid malignancies, will be screened with the G8 and mG8 prior to receiving 1st line antineoplastic treatment. Patients will contribute medical record data including; cancer type, Charlson comorbidity index score, performance status, and treatment intent, type, and dosage, at baseline. Patients will complete QoL questionnaires (EORTC QLQ-C30 and ELD-14) at baseline, 3, 6, 9, and 12-months follow-up. Two functional measurements (the 30-s chair stand test and the handgrip strength test) will be conducted at baseline to assess the added predictive and prognostic value. At 12 months follow-up, initially administered treatment and treatment adherence will be recorded and assessed with generalized linear models, while overall survival and cancer-specific survival will be assessed using survival analysis models with time-varying covariates. The relationship between frailty (G8 ≤ 14, mG8 ≥ 6) and QoL within 12 months will be examined using mixed regression models. DISCUSSION: Geriatric oncology screening may identify a subgroup of older patients with frailty, at risk of experiencing diminishing QoL and poor treatment adherence. With the proposed screening program, patients who require treatment modification and additional support to maintain their QoL may be identified. It is our hope, that these insights may facilitate the formation of national guidelines for the treatment of older patients with cancer. Registration:NCT04644874.

FDG-PET/CT in high-risk primary breast cancer-a prospective study of stage migration and clinical impact.

PURPOSE: To investigate the clinical impact of FDG-PET/CT for staging and treatment planning in high-risk primary breast cancer. METHODS: Women with high-risk primary breast cancer were enrolled between September 2017 and August 2019 at Odense University Hospital, Denmark. Conventional mammography with/without MRI was performed before staging by FDG-PET/CT. We studied the accuracy of FDG-PET/CT for the detection of distant metastases, the effect on the change of treatment, and the prevalence of incidental findings. Biopsy and follow-up were used as a reference standard for the accuracy analysis. RESULTS: Of 103 women, 24 (23%) were diagnosed with distant metastases by FDG-PET/CT. Among these, breast surgery was omitted in 18 and could have been spared in six. Another sixteen (16%) patients were upstaged to more advanced loco-regional disease, leading to more extensive radiotherapy. Sensitivity and specificity for diagnosing distant metastases were 1.00 (95% confidence interval: 0.86-1.00) and 0.95 (0.88-0.99), respectively. Twenty-nine incidental findings were detected in 24 women (23%), leading to further examinations in 22 and diagnosis of eight (8/22, 36%) synchronous diseases: cancer (n = 4), thyroiditis (n = 2), aorta aneurysm (n = 1), and meningioma (n = 1). CONCLUSIONS: FDG-PET/CT had a substantial impact on staging and change of treatment in women with high-risk primary breast cancer, and further examination of incidental findings was considered clinically relevant. Our findings suggest that FDG-PET/CT should be considered for primary staging in high-risk primary breast cancer to improve treatment planning.