Nurse navigation, symptom monitoring and exercise in vulnerable patients with lung cancer: feasibility of the NAVIGATE intervention.

We developed the Navigate intervention to improve survival among vulnerable lung cancer patients. In this intervention-only study, we examined feasibility in terms of recruitment, retention, attendance, adherence, and acceptability to specify adjustments to study procedures and intervention components prior to a randomized trial. The Navigate intervention includes nurse navigation, patient-reported outcomes, and physical exercise. Patients ≥ 18 years old, diagnosed with non-small cell lung cancer at any stage, with performance status ≤ 2, eligible for cancer treatment and vulnerable according to a screening instrument were included. The recruitment goal of eligible patients was 40% while the retention goal was 85%. The predefined cut-offs for sufficient attendance and adherence were ≥ 75%. Acceptability was evaluated by semi-structured interviews with participants, nurse navigators, and physiotherapists. Seventeen (56%) out of 30 screened patients were considered vulnerable and eligible for the study, 14 (82%) accepted participation, and 3 (21%) were subsequently excluded due to ineligibility, leaving 11 patients. Four patients dropped out (36%) and four patients died (36%) during follow-up and 3 (27%) were retained. All 11 patients participated in nurse sessions (mean 16, range 1-36) with 88% attendance and dialogue tools being applied in 68% of sessions. Ninety-one percent of patients responded to PROs (mean of 9 PROs, range 1-24) with 76% of the PRO questionnaires used (attendance) and 100% adherence (completion of all questions in PRO questionnaires), and 55% participated in exercise sessions with 58% attendance and 85% adherence. We identified important barriers primarily related to transportation, but overall acceptability was high. The Navigate intervention was feasible with high participation, acceptability and satisfactory adherence. Retention and exercise attendance were low, which resulted in adjustments.Trial registration: The feasibility study was initiated prior to the multicenter randomized controlled trial registered by ClinicalTrials.gov (number: NCT05053997; date 23/09/2021).

Who are the vulnerable lung cancer patients at risk for not receiving first-line curative or palliative treatment?

BACKGROUND: To identify non-small-cell lung cancer (NSCLC) patients in need of comprehensive support, we examined the association between patient and disease-related factors of vulnerability related to not receiving guideline-recommended treatment. MATERIAL AND METHODS: We identified 14,597 non-small-cell lung cancer (NSCLC) patients with performance status <3 during 2013-2018 in the Danish Lung Cancer Registry. Multivariate logistic regression models were used to estimate Odds Ratios (ORs) and 95% confidence intervals (CIs) for receiving guideline-recommended treatment according to stage, comorbidities, age, performance status, long distance to hospital, cohabitation status, education and alcohol abuse. RESULTS: 21% of stage I-IIIA NSCLC patients did not receive curative treatment while 10% with stage IIIB-IV did not receive any oncological therapy. Factors associated with reduced likelihood of receiving curative treatment included: advanced stage (OR = 0.45; 95% CI = 0.42-0.49), somatic comorbidity (OR = 0.72; 95% CI = 0.63-0.83), age ≥ 80 years (OR = 0.59; 95% CI = 0.55-0.64), performance status = 2 (OR = 0.33; 95% CI = 0.28-0.39) and living alone (OR = 0.79; 95% CI = 0.69-0.90). Results were similar for stage IIIB-IV NSCLC patients, although a statistically significant association was also seen for long distances to the hospital (OR = 0.71; 95% CI = 0.58-0.86). CONCLUSIONS: Several factors are associated with not receiving guideline-recommended NSCLC treatment with age, performance status, comorbidity and stage being most predictive of no treatment receipt. Efforts should be made to develop support for vulnerable lung cancer patients to improve adherence to optimal first-line therapy.

Understanding quality data correctly: a randomized comparison of presentation formats among cancer patients and relatives.

Background: Patient representatives are increasingly engaged in quality in health care, and even though quality data are publicly available, correct interpretation may be challenging. We designed a randomized study with the primary aim to examine the association between preferred data presentation format and the interpretation of quality data among cancer patients and relatives.Material and methods: Surveys were distributed to the Danish Cancer Society Citizens' Panel between 31 March and 14 April 2019 and 55% completed the survey (N = 464) including six storyboards that presented authentic quality data in table format, league table and point estimates. The storyboards were randomized to expose participants to the data in the three different formats and in varying presentation order. Logistic regression models were used to calculate Odds Ratios (ORs) and 95% confidence intervals (CIs) for the association between preferred presentation format, health literacy, education and cohabitation status as exposures and interpretation of quality data as outcome.Results: The majority of participants (97%) had high literacy and 57% had a medium or long higher education. A total of 60% found the questions difficult or very difficult and 33% were not able to correctly interpret at least one format. Correct interpretation was associated with preferred league table (OR = 1.62; 95% CI = 1.04-5.52) and if the data was presented in the preferred format. Medium and long education were associated with correct interpretation of at least one format (OR = 1.93; 95% CI = 1.16-3.21 and OR = 3.89; 95% CI = 1.90-7.95, respectively) while health literacy and cohabitation status were not.Conclusions: More than one third of the participants were not able to correctly interpret the data and the understanding of quality data improved with longer education and if the data was presented in the preferred format. Decision-makers should carefully consider displaying quality data according to preferred presentation format and to guide interpretation for individuals with short education.

NAVIGATE: improving survival in vulnerable patients with lung cancer through nurse navigation, symptom monitoring and exercise - study protocol for a multicentre randomised controlled trial.

INTRODUCTION AND AIM: Low socioeconomic position (SEP) has been shown to be strongly associated with impaired lung cancer survival. Barriers related to receiving recommended treatment among patients with lung cancer with low SEP may include adverse health behaviour and limited physical and psychosocial resources influencing the ability to react on high-risk symptoms and to navigate the healthcare system. To address the underlying factors that drive both decisions of treatment, adherence to treatment and follow-up in vulnerable patients with lung cancer, we developed the Navigate intervention. The aim of this randomised controlled trial is to investigate the effect of the intervention on survival (primary outcome), lung cancer treatment adherence, health-related quality of life and other psychosocial outcomes as well as health costs and process evaluation (secondary outcomes) in a study population of vulnerable patients with lung cancer. METHODS AND ANALYSIS: This two-armed multicentre randomised trial will recruit patients from five lung cancer clinics in Denmark identified as vulnerable according to a screening instrument with nine clinical and patient-reported vulnerability criteria developed for the study. We will enrol 518 vulnerable patients >18 years old diagnosed with non-small cell lung cancer at all stages with a performance status <2. Participants will be randomly allocated to either standard treatment and intervention or standard treatment alone. The Navigate intervention is based on principles from motivational interviewing and includes three components of nurse navigation, systematic monitoring of patient-reported outcomes (PROs) and physical exercise in a person-centred delivery model. Data will be collected at baseline and 3, 6, 12 months after randomisation using questionnaires, clinical data and physical function tests. ETHICS AND DISSEMINATION: Ethics Committee, Region Zealand (SJ-884/EMN-2020-37380) and the Data Protection Agency in Region Zealand (REG-080-2021) approved the trial. Participants will provide written informed consent. Results will be reported in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05053997.

A case-control study of the joint effect of reproductive factors and radiation treatment for first breast cancer and risk of contralateral breast cancer in the WECARE study.

OBJECTIVE: To examined the impact of reproductive factors on the relationship between radiation treatment (RT) for a first breast cancer and risk of contralateral breast cancer (CBC). METHODS: The Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study is a multi-center, population-based case-control study where cases are women with asynchronous CBC (N = 1521) and controls are women with unilateral breast cancer (N = 2211). Rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression to assess the independent and joint effects of RT (ever/never and location-specific stray radiation dose to the contralateral breast [0, >0-<1Gy, ≥1Gy]) and reproductive factors (e.g., parity). RESULTS: Nulliparous women treated with RT (≥1Gy dose) were at increased risk of CBC compared with nulliparous women not treated with RT, although this relationship did not reach statistical significance (RR = 1.34, 95% CI 0.87, 2.07). Women treated with RT who had an interval pregnancy (i.e., pregnancy after first diagnosis and before second diagnosis [in cases]/reference date [in controls]) had an increased risk of CBC compared with those who had an interval pregnancy with no RT (RR = 4.60, 95% CI 1.16, 18.28). This was most apparent for women with higher radiation doses to the contralateral breast. CONCLUSION: Among young female survivors of breast cancer, we found some evidence suggesting that having an interval pregnancy could increase a woman's risk of CBC following RT for a first breast cancer. While sampling variability precludes strong interpretations, these findings suggest a role for pregnancy and hormonal factors in radiation-associated CBC.

Preventive drug therapy and contralateral breast cancer: summary of the evidence of clinical trials and observational studies.

Background: Breast cancer patients have a lifelong 2-4-fold increased risk of developing a second primary tumor in the contralateral breast compared with the risk for a first primary breast cancer in the general female population. Prevention of contralateral breast cancer (CBC) has received increased attention during recent decades. Here, we summarize and discuss the available literature on drug preventive therapy and CBC.Results: The endocrine-targetting drugs, tamoxifen and aromatase inhibitors are used as standard adjuvant treatment for estrogen receptor (ER)-positive breast cancer. Both are associated with relative risk reductions of CBC of up to 50%, but incur serious side effects. Several prescription drugs originally developed for other purposes, including bisphosphonates, statins, non-steroidal anti-inflammatory drugs, metformin, anti-hypertensives and retinoids, have shown anti-cancer activity in preclinical models. However, results of observational studies on CBC are sparse and inconsistent, with only statins demonstrating promise as preventive agents and a potential treatment option for ER-negative breast cancer patients.Conclusion: Future studies are needed to assess the effect of statins in risk reduction and to identify other drugs with chemopreventive potential against CBC. Eventually, efforts must be directed towards identifying those breast cancer patients likely to benefit most from specific preventive therapies.

Statin use and risk of contralateral breast cancer: a nationwide cohort study.

BACKGROUND: Statins have demonstrated antineoplastic effects in breast cancer cell lines, particularly in oestrogen receptor (ER)-negative cell lines. However, epidemiological studies have not supported a preventive effect of statin use against breast cancer. Therefore, we examined the association between statin use and contralateral breast cancer (CBC) risk among women with breast cancer. METHODS: We identified 52,723 women with non-metastatic breast cancer during 1996-2012 from the Danish Breast Cancer Group database. We defined time-varying post-diagnosis statin use as minimum two prescriptions lagged by 1 year. Cox regression analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CBC associated with statin use. RESULTS: Statin use was associated with a lower CBC risk (HR = 0.88; 95% CI = 0.73-1.05). The inverse association was strongest for long-term use overall (HR = 0.64; 95% CI = 0.43-0.96), although the HR specifically for long-term consistent use and high-intensity use approached unity. Among ER-negative breast cancer patients, statin use was associated with a CBC risk reduction (HR = 0.67; 95% CI = 0.45-1.00). CONCLUSIONS: We found some indication that statins reduce the risk of CBC. Further evaluations are needed to disentangle the equivocal results for long-term use and to establish if ER-negative breast cancer patients may benefit most from statin use.

Mortality after contralateral breast cancer in Denmark.

PURPOSE: How a second breast cancer diagnosis affects survival in comparison with unilateral breast cancer (UBC) is unclear. Prognostic factors for contralateral breast cancer (CBC) are also not well established. We aimed to investigate the survival pattern after CBC with particular focus on time between first and second breast cancer diagnosis and age at CBC diagnosis. METHODS: Within the nationwide Danish Breast Cancer Cooperative Group database, we identified 68,466 breast cancer patients diagnosed during 1978-2012. Patients who subsequently developed CBC were identified in a previously established database (N = 3004). Patients were followed for breast cancer-specific death in the Danish Register of Causes of Death until 2015. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard regression models. Cumulative breast cancer mortality from date of CBC was estimated using the Aalen-Johansen method. RESULTS: Compared with UBC patients, the rate of dying from breast cancer was more than twofold higher following a CBC diagnosis, after adjustment for age, period, tumor characteristics, and treatment of the first breast cancer (HR 2.48; 95% CI 2.31-2.66). Short time interval (< 5 years) was associated with higher breast cancer-specific mortality after CBC among patients < 70 years at CBC diagnosis compared with longer time intervals, but not among patients ≥ 70 years at CBC diagnosis. CONCLUSION: Breast cancer-specific mortality rates were markedly higher after compared with before a CBC diagnosis. We found higher breast cancer-specific mortality after CBC associated with a short interval between diagnoses among patients diagnosed with CBC before age 70 years.

Agreement between self-reported and register-based cardiovascular events among Danish breast cancer survivors.

PURPOSE: We examined the degree of over- and under-reporting of cardiovascular diseases (CVDs) among female breast cancer survivors comparing self-reports to diagnostic codes from the Danish National Patient Register (NPR). METHODS: The study comprised 357 Danish breast cancer patients from the WECARE study who completed a telephone interview concerning CVDs. Disease diagnoses for these women were obtained from the NPR. Agreement was calculated as the number of diagnoses that were both self-reported and in the NPR divided by (1) number of self-reported diagnoses (over-reporting) or (2) number of diagnoses in the NPR (under-reporting). RESULTS: In total, 68 women reported 96 specific cardiovascular outcomes of which 56 (58%) were found in the NPR. Ninety cardiovascular diagnoses were found in the NPR of which 56 (62%) were specifically reported at the interview. There was 80% agreement as to the occurrence of a cardiovascular diagnosis overall. Of 289 women reporting no CVD, 273 (94%) had no diagnoses in the NPR. CONCLUSIONS: Breast cancer survivors seem to report absence of CVD accurately, but they both over-report and under-report specific cardiovascular diagnoses. Using a broader definition of CVDs improves the agreement between self-reported and NPR data. IMPLICATIONS FOR CANCER SURVIVORS: Determining how cancer treatments affect the risk of cardiovascular morbidities is essential, and the development of high-quality methods for collecting such data is critical. While self-reported data are adequate for assessing the presence of any CVD condition, medical record review will yield higher quality data on specific CVD conditions.

Alcohol consumption and cigarette smoking in combination: A predictor of contralateral breast cancer risk in the WECARE study.

Alcohol drinking and, to a lesser extent, cigarette smoking are risk factors for a first primary breast cancer. Information on these behaviours at diagnosis may contribute to risk prediction of contralateral breast cancer (CBC) and they are potentially modifiable. The WECARE Study is a large population-based case-control study of women with breast cancer where cases (N = 1,521) had asynchronous CBC and controls (N = 2,212), matched on survival time and other factors, had unilateral breast cancer (UBC). Using multivariable conditional logistic regression to estimate rate ratios (RR) and 95% confidence intervals (CI), we examined the risk of CBC in relation to drinking and smoking history at and following first diagnosis. We adjusted for treatment, disease characteristics and other factors. There was some evidence for an association between CBC risk and current drinking or current smoking at the time of first breast cancer diagnosis, but the increased risk occurred primarily among women exposed to both (RR = 1.62, 95% CI 1.24-2.11). CBC risk was also elevated in women who both smoked and drank alcohol after diagnosis (RR = 1.54, 95% CI 1.18-1.99). In the subset of women with detailed information on amount consumed, smoking an average of ≥10 cigarettes per day following diagnosis was also associated with increased CBC risk (RR = 1.50, 95% CI 1.08-2.08; p-trend = 0.03). Among women with a diagnosis of breast cancer, information on current drinking and smoking could contribute to the prediction of CBC risk. Women who both drink and smoke may represent a group who merit targeted lifestyle intervention to modify their risk of CBC.

Systemic therapy for breast cancer and risk of subsequent contralateral breast cancer in the WECARE Study.

BACKGROUND: Treatment with tamoxifen or chemotherapy reduces the risk of contralateral breast cancer (CBC). However, it is uncertain how long the protection lasts and whether the protective effect is modified by patient, tumor, or treatment characteristics. METHODS: The population-based WECARE Study included 1521 cases with CBC and 2212 age- and year of first diagnosis-matched controls with unilateral breast cancer recruited during two phases in the USA, Canada, and Denmark. Women were diagnosed with a first breast cancer before age 55 years during 1985-2008. Abstraction of medical records provided detailed treatment information, while information on risk factors was obtained during telephone interviews. Risk ratios (RRs) and 95 % confidence intervals (CIs) for CBC were obtained from multivariable conditional logistic regression models. RESULTS: Compared with never users of tamoxifen, the RR of CBC was lower for current users of tamoxifen (RR = 0.73; 95 % CI = 0.55-0.97) and for past users within 3 years of last use (RR = 0.73; 95 % CI = 0.53-1.00). There was no evidence of an increased risk of estrogen receptor-negative CBC associated with ever use of tamoxifen or use for 4.5 or more years. Use of chemotherapy (ever versus never use) was associated with a significantly reduced RR of developing CBC 1-4 years (RR = 0.59; 95 % CI = 0.45-0.77) and 5-9 years (RR = 0.73; 95 % CI = 0.56-0.95) after first breast cancer diagnosis. RRs of CBC associated with tamoxifen or with chemotherapy use were independent of age, family history of breast cancer, body mass index and tumor characteristics of the first breast cancer with the exception that the RR of CBC was lower for lobular histology compared with other histologies. CONCLUSION: Our findings are consistent with previous studies showing that treatment with tamoxifen or chemotherapy is associated with a lower risk of CBC although the risk reduction appears to last for a limited time period after treatment is completed.

Incidence of metachronous contralateral breast cancer in Denmark 1978-2009.

BACKGROUND: Incidence of contralateral breast cancer (CBC) is much less studied than primary breast cancer. We aimed to assess incidence rates of CBC in relation to age, calendar period and time since first breast cancer. METHODS: Using the nationwide Danish Cancer Registry, we identified 85 863 women with a first primary invasive breast cancer without distant metastases in Denmark during 1978-2009. Among these, 3120 women developed metachronous CBC. Crude incidence rates for CBC were calculated by age and calendar period at first breast cancer as well as time since first breast cancer. Mutual adjustments were made by use of Poisson regression models. RESULTS: The incidence of CBC decreased with increasing age at first breast cancer. Before 1998, incidence rates of CBC showed little variation. The rates decreased by period of first primary from 546 per 10(5) person-years in 1993-97 to 328 per 10(5) person-years in 2003-09. After adjustment for age and calendar period, no clear trend was observed in the overall incidence according to time since first breast cancer. CONCLUSIONS: Occurrence of cancer in the contralateral breast seems to be rather independent of time passed since the first primary. The finding of a decreasing incidence of CBC after 1997 is likely to be due to more women receiving systemic adjuvant therapy such as tamoxifen and longer duration of this treatment as well as the introduction of aromatase inhibitors.

Risk for second primary non-breast cancer in pre- and postmenopausal women with breast cancer not treated with chemotherapy, radiotherapy or endocrine therapy.

INTRODUCTION: We investigated the risk for a second primary cancer in pre- and postmenopausal women with breast cancer treated by surgery alone, to assess the importance of non-treatment factors and menopausal status. PATIENTS AND METHODS: The cohort comprised 14,151 women with breast cancer diagnosed during 1977-2006, who did not receive radiotherapy or systemic adjuvant therapy. They were identified in the nationwide clinical database of the Danish Breast Cancer Cooperative Group. The women were followed for a second primary cancer other than breast cancer in the Danish Cancer Registry, and risk was quantified as standardised incidence ratios (SIRs). RESULTS: Women with breast cancer diagnosed before menopause had an 18% greater overall risk for a second primary non-breast cancer than the general female population (95% confidence interval [CI], 1.06-1.32). The excess was confined to cancers of the endometrium (1.5; 95% CI, 1.0-2.0) and ovaries (1.8; 95% CI, 1.2-2.4). Rare histological subtypes of breast cancer were associated with these two cancer sites. Women with breast cancer after menopause had no overall excess risk for a second cancer (SIR, 0.98; 95% CI, 0.92-1.04). CONCLUSION: An excess risk for second non-breast cancers related to non-treatment factors is seen primarily in breast cancer patients who were premenopausal at diagnosis.