Journal of Geriatric Oncology

Do age and comorbidity impair recovery during two years after treatment for endometrial cancer?

A better understanding of the impact of age and comorbidity on health-related quality of life (HRQoL) may improve treatment decision-making in patients with endometrial cancer. We investigated whether either age or comorbidity is more strongly associated with changes in HRQoL over time. Endometrial cancer patients (n = 296) were invited to complete questionnaires after initial treatment and after 6, 12 and 24 months follow-up. Patients were divided into subgroups according to age (<60, 60-75 and ≥75 years) and according to comorbidity (0, 1, 2 or ≥3). HRQoL was measured with the five EORTC QLQ-C30 functioning scales. Linear mixed models were performed for the different subgroups to assess changes in HRQoL over time. HRQoL was also compared to longitudinal outcomes from an age- and gender-matched normative population. The first questionnaire was returned by 221 patients (75%) of whom six were excluded due to progressive disease. Changes in HRQoL were mainly associated with cumulative comorbidity burden and not with age. Patients with comorbidity reported deterioration of physical and role functioning between 12 and 24 months. Compared to the normative population, patients initially scored higher on physical and role functioning, but at 24 months outcomes were no longer different. Cumulative comorbidity burden was more strongly associated with deterioration of HRQoL than patient's age. Therefore, patients with endometrial cancer and multiple comorbid conditions require careful follow-up of HRQoL after treatment.

The pervasive impact of frailty on ovarian cancer care and the role of prehabilitation: Qualitative perspectives of key stakeholders

We performed a qualitative study to explore key stakeholders' perspectives about the impact of frailty on ovarian cancer care and evaluate a candidate prehabilitation intervention. We conducted semi-structured interviews with patient-caregiver dyads and multi-disciplinary clinicians. Patients were ≥ 50 years of age with a new diagnosis of advanced stage (III/IV) ovarian cancer who received cancer-directed treatment (chemotherapy and/or surgery) during the past year and met criteria as pre-frail or frail using the FRAIL scale. We used a semi-structured interview guide to elicit participants' views on frailty, nutrition, physical therapy, and a candidate prehabilitation intervention. We used inductive and deductive approaches to code and analyze interviews and identify emergent themes and patterns. Ten patients and caregivers (five dyads) and 10 providers were interviewed. We identified four themes: (1) frailty screening is essential to prevent over- and under-treatment, but underused; (2) stakeholders preferred a multidisciplinary approach to providing tailored care for frail patients over a candidate prehabilitation intervention; (3) patient, family caregiver, and clinician stakeholders reported multiple barriers to prehabilitation programs, including concerns about selection bias, and (4) frail patients and family members are vulnerable and require more psychosocial support. We identified significant barriers to prehabilitation interventions for frail patients with ovarian cancer; initiatives to increase frailty screening and provide tailored multi-disciplinary approaches may have a greater impact.

Impact of FRAilty screening and Geriatric assessment and INtervention in older patients with epithelial Ovarian Cancer: A multicenter randomized clinical trial protocol (FRAGINOC)

Radical surgery combined with chemotherapy is the only potential curative treatment of patients with advanced epithelial ovarian cancer (EOC). However, 43% of older Danish patients with EOC are not referred to surgery due to frailty, age, or fear of complications. Comprehensive geriatric assessment (CGA) has demonstrated ability to reduce frailty in older patients, but there is a knowledge gap regarding its effect before or during treatment in older adults with EOC. This protocol presents a randomized controlled trial (RCT), which evaluates the effect of CGA-based interventions including individualized physical exercise therapy in older adults with EOC during neoadjuvant chemotherapy (NACT). This RCT will include patients aged ≥70 years with primary EOC referred to NACT. Patients will be randomized 1:1 to intervention or standard of care, along with neoadjuvant antineoplastic treatment. Stratification for performance status and center of inclusion will be performed. In the intervention arm, a geriatrician will perform CGA and corresponding geriatric interventions and patients will undergo an individualized home-based exercise program managed by a physiotherapist. All patients will be evaluated with Geriatric-8, modified Geriatric-8, clinical frailty scale, and physical tests at randomization. Predictive values (positive/negative) will be evaluated for CGA detected impairments. The primary endpoint is the proportion of patients referred to interval debulking surgery (IDS). Secondary endpoints include the proportion who complete oncological treatment, improvements in physical tests, quality of life measured by European Organization for Research and Treatment of Cancer-Quality of Life questionnaires at inclusion, after three cycles of chemotherapy, and at end of chemotherapy treatment. Furthermore, the association between results of geriatric screening tests, CGA, and physical tests with complication rate and progression free survival will be examined. The primary outcome will be analyzed with logistic regression in the intention-to-treat population. Power calculations reveal the need to enroll 216 patients. The present study examines whether CGA-based interventions including individualized physical exercise can increase the referral rate for potential curative IDS in older patients with EOC. If successful, this will result in more patients undergoing surgery and completing chemotherapy, preventing complications, and ultimately improving quality of life and survival. The study setup may establish the basis for direct clinical implementation if proven effective.

Impact of age, comorbidity, and polypharmacy on receipt of systemic therapy in advanced cancers: A retrospective population-based study

Breast cancer associated pathogenic variants among women 61 years and older with triple negative breast cancer

Women with triple negative breast cancer (TNBC) have a high prevalence of BRCA1 mutations, and current clinical guidelines recommend genetic testing for patients with TNBC aged ≤60 years. However, studies supporting this recommendation have included few older women with TNBC. Genetic testing results from women aged >60 years with TNBC enrolled in the Clinical Cancer Genomics Community Research Network (CCGCRN) registry were included in this analysis. Prevalence of breast cancer-associated pathogenic variants (PVs) was compared across age groups. We identified 151 women with TNBC aged >60 years (median 65 years; SD 5.3). Of these, 130 (86%) underwent genetic testing, and a breast cancer-associated PV was identified in 16 (12.3%; 95% CI 7-19): BRCA1 (n = 6), BRCA2 (n = 5), PALB2 (n = 2), ATM (n = 1) and RAD51C (n = 2). We found no differences in the proportion of patients with close blood relatives with breast (≤50 years) or ovarian cancer (any age) between PV carriers (37.5%) and non-carriers (34.2%) (p = 0.79). Among PV's carriers, the proportion of older women with a BRCA1 PV was lower when compared to younger women (37.5% vs 77.2%; p 60 years with TNBC undergoing genetic testing, including greater representation of BRCA2. These results suggest that older women with TNBC should be offered genetic testing, and that their exclusion based on chronologic age alone may not be appropriate.

The influence of polypharmacy, potentially inappropriate medications, and drug interactions on treatment completion and prognosis in older patients with ovarian cancer

Older patients with cancer are at increased risk of exposure to polypharmacy (PP), potential drug interactions (PDIs), and Potentially inappropriate Medications (PIMs). Objectives of this study were to describe PP, PIMs, and PDIs, and to analyse the associations with completion of 1st line chemotherapy and prognosis in ovarian cancer (OC) patients. Registry-based study including a 10-year national cohort of patients diagnosed with epithelial OC in Denmark. Descriptive statistics, multivariate logistic regression analyses, Kaplan-Meier, and Cox regression analyses were performed to analyse the data. A total of 3795 patients were included and described. Further analyses were performed on 2219 patients registered with a date of surgery and combination chemotherapy with platinum and a taxane or platinum monotherapy. Exposure to ≥2 PDIs was associated with not completing chemotherapy, odds ratio (OR) 2.27 (1.18-4.37). Major and extensive PP were associated with increased mortality at 0-6 months after diagnosis, HR 3.15(1.59-6.22) and 5.43(2.34-12.6), respectively. PIMs were associated with increased mortality from six months after diagnosis. At 6-12 months: hazard ratio (HR) 1.50(1.06-2.11) and 2.38(1.25-4.50) with 1-2 and ≥ 3 PIMs, respectively. At 12 months: HR 2.08(1.31-3.29) with ≥3 PIMs. Age was not associated with treatment completion. Drug use influences treatment completion and prognosis in OC patients. A thorough review of patients' medications aiming to minimize the number of PIMs and PDIs might improve the course of these patients' disease.

Time trends assessment of cervical cancer characteristics in Guangzhou, 2010–2021: Is the age at diagnosis increasing over time?

Radiotherapy utilisation rates for patients with cancer as a function of age: A systematic review

There is an increasing incidence of cancer in older people, but limited data on radiotherapy uptake, and in particular, radiotherapy utilisation (RTU) rates. The RTU rate for older adults with cancer may be lower than recommended due to lower tolerance for radiotherapy as well as additional comorbidities, reduced life expectancy and travel for treatment. Radiotherapy use must be aligned with best available, age-specific evidence to ensure older adults with cancer receive optimal benefit without harms. A systematic review was conducted to synthesise the published data on the actual RTU rate for patients with cancer as a function of age. MEDLINE and EMBASE were systematically searched to identify relevant population-based and hospital-based cohort studies on radiotherapy utilisation for all age groups, published in English, from 1 January 1990 to 1 July 2020. We focused on the following common cancers in older adults for which radiotherapy is recommended: breast, prostate, lung, rectal cancer, glioblastoma multiforme (GBM), and cervical cancer. Age-specific radiotherapy utilisation data were extracted and analysed as a narrative synthesis. From 2606 studies screened, 75 cohort and population-based studies were identified with age-specific radiotherapy utilisation data. The total number of patients in the 75 studies was 4,792,138. The RTU rate decreased with increasing age for all tumour sites analysed, except for patients receiving curative radiotherapy as definitive treatment for prostate or cervical cancer. This reduction with increasing age was demonstrated in both palliative and curative settings. There is a global reduction in radiotherapy utilisation with increasing age for most tumour sites. The reduction in delivery of radiotherapy warrants further examination and evidence-based guidelines specific to this population.

Age and comorbidity in relation to treatment and survival outcomes in triple-negative breast cancer: A Swedish nationwide registry-based study

Impact of surgery and chemotherapy timing on outcomes in older versus younger epithelial ovarian cancer patients: A nationwide Danish cohort study

To explore differences in surgical complexity, chemotherapy administration, and treatment delays between younger and older Danish patients with epithelial ovarian cancer (EOC). We included a nationwide cohort diagnosed with EOC from 2013 to 2018. We described surgical complexity and outcomes, the extent of chemotherapy and treatment delays stratified by age (0 cm compared to younger patients. Furthermore, older patients were less often treated with chemotherapy. Older patients had PDS later than younger. We did not find any differences between age groups concerning treatment delays. Two-year cancer-specific survival differed significantly between age groups regardless of curatively intended treatment. This study demonstrates that older patients are treated less actively concerning surgical and oncological treatment than younger patients, leading to worse cancer-specific survival. Older patients do not experience more treatment delays than younger ones.

Frailty and treatment decisions in older patients with vulvar cancer: A single-center cohort study

Vulvar cancer is a disease that mainly affects older women. Frailty is an important predictor of outcomes and geriatric assessment can help tailor treatment decisions and improve outcomes. This study aims to assess the prevalence of frailty in older women with vulvar cancer, and how it relates to integrated geriatric care and treatment according to the oncological guidelines. A single-center cohort study was performed, among patients 70 years and older, who were diagnosed with vulvar cancer at Leiden University Medical Center, between January 2012 and May 2020. Data on geriatric assessment, treatment decision-making and treatment-related outcomes were collected. Our study included 114 patients. Mean age was 79.7 years, and 52 patients (45.6%) were frail. Of the frail patients, 42.0% were referred to a geriatrician. In eight of these cases, the geriatrician was actively involved in weighing the benefit and harm of standard oncological treatment versus de-escalated treatment. Frailty, higher age, impairment in the somatic domain, cognitive impairment, and functional dependency were associated with referral to a geriatrician and with active involvement of a geriatrician in decision making. In 26 of frail patients (50.0%) oncological treatment was de-escalated. Frailty, higher age, impairment in the somatic domain, cognitive impairment, and functional dependency were associated with de-escalation of treatment. De-escalated treatment did not compromise survival. Frailty is prevalent among older women with vulvar cancer and is associated with referral to a geriatrician and de-escalation of oncological treatment. While this reflects that it is deemed important to tailor treatment decision for frail patients, most frail patients are not routinely evaluated by a geriatrician. Further multidisciplinary collaboration and research is necessary to optimize tailored treatment decisions for this patient group.

Hospital use and cancer treatment by age and socioeconomic status in the last year of life: A Norwegian population-based study of patients dying of cancer

Real-world ovarian cancer care and its survival impact on older adults: An observational study from the Australian National Gynae-Oncology Registry (NGOR)

Women aged ≥70 years with ovarian cancer (OC) may experience variations in care compared to best practice guidelines, and their five-year survival is significantly lower compared to women aged <70 years. The National Gynae-Oncology Registry (NGOR) is Australia's first clinical quality registry (CQR) for gynaecological cancers, measuring patterns of care using 15 OC clinical quality indicators (CQIs) reflecting evidence-based practice. This study aimed to compare adherence to CQIs for older versus younger groups with newly diagnosed OC and evaluate differences in 5-year overall survival (OS). This is a multi-centre, observational study utilizing NGOR data for women with newly diagnosed OC at participating sites (May 2017 to July 2022). Demographics, CQIs, and clinical variables were compared between women aged ≥70 years (older group) and those aged <70 years (younger group). Five-year OS was estimated. A total of 1628 women were eligible. Median OS was 3.37 years (95 % CI: 3.05-3.86 years) in the ≥70 group versus not reached in the younger group aged <70 (95 % CQI: 5.95 - n/a years). Compared to the younger group, older women less frequently received first-line platinum-taxane doublet chemotherapy (69.1 % vs 91.6 %, p < 0.001) and first-line chemotherapy with a platinum-taxane doublet plus bevacizumab (18.9 % vs 29.9 %, p = 0.02). Older women were less likely to achieve primary surgery with no macroscopic residue (46.4 % vs 60.8 %, p = 0.03) and had lower clinical trial enrolment (15.5 % vs 21.7 %, p = 0.005). After adjusting for ECOG Performance Status, histological sub-type, cancer stage, and treatment group, five-year OS remained significantly lower in the older women with an adjusted HR for death 1.50 (95 % CI: 1.27-1.76, p = 0.001). Significant differences in care were observed in older women with OC, notably in achieving complete primary surgical cytoreduction, utilization of standard chemotherapy regimens, and trial enrolment. Survival for older women remains significantly lower than for younger women after adjustment. These findings highlight specific areas for potential quality improvement in the care of older Australian women with OC.

Relative dose intensity and overall treatment time in older patients with cervical cancer treated with concurrent chemoradiotherapy

Trends in the use of granulocyte colony stimulating factors for older patients with cancer, 2010 to 2019

Patient characteristics and health system factors associated with adjuvant radiation therapy receipt in older women with early-stage endometrial cancer

Among women with early-stage endometrial cancer (EC), age, stage, grade, and histology are used to determine fitness for adjuvant radiation therapy (RT) administration. We examined non-cancer factors associated with adjuvant RT receipt in older women with early-stage EC. Using data from the Surveillance Epidemiology and End Results cancer registry program linked with Medicare claims, we identified 25,654 women (aged ≥66 years) diagnosed with first primary stage I-II EC during 2004-2017 who underwent a hysterectomy. Diagnosis and procedure codes were used to identify adjuvant RT claims filed for the seven-month period post-hysterectomy. Multivariable log-binomial regression was used to estimate adjuvant RT prevalence associated with patient characteristics and health system factors after adjustment for age, frailty, and endometrial factors. Adjuvant RT was less commonly administered to Asian American and Pacific Islander patients than non-Hispanic White patients (Prevalence ratio [PR], 0.84; 95% confidence interval [CI], 0.73 to 0.97). Compared to women treated in the Northeast region, women treated other regions of the US were less likely to undergo adjuvant RT (PR, 0.75; 95% CI, 0.71 to 0.79). Residing in rural or high neighborhood-poverty counties was associated with lower adjuvant RT administration. Higher comorbidity score was not associated with reduced prevalence of adjuvant RT receipt; however, women with high probability of predicted probability of frailty were less likely to undergo adjuvant RT (PR, 0.67; 95% CI, 0.55 to 0.81) compared to women with low probability of frailty. Women who received lymph node assessment were more likely to undergo adjuvant RT compared to women who did not (PR, 1.43; 95% CI, 1.34 to 1.51). Women treated by a gynecologic oncologist were more likely to undergo adjuvant RT compared to women treated by a non-gynecologic oncologist (PR 1.09; 95% CI, 1.04 to 1.14). Adjuvant RT was more commonly administered to women treated in larger academic hospitals. Findings suggest that various non-cancer factors affect the delivery of adjuvant RT to older women with early-stage EC in real-world oncology practice. Advancing our understanding of factors associated with adjuvant RT administration may help expand equitable access to RT.