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.

Palliative medical cancer treatment of the elderly.

Due to demographic changes the incidence of older patients with cancer will increase. The complexity of systemic treatment of cancer is also evolving. Older patients with cancer are underrepresented in clinical trials and do often not represent the older population treated in real-world setting. Knowledge on how to treat older patients with cancer is sparse and mostly based on pooled analyses from larger trials including older fit patients. Only few randomised trials include older patients with frailty. Clinical trials dedicated to older or frail patients with cancer are still an unmet need, as argued in this review.

Leave no one behind: A global survey of the current state of geriatric oncology practice by SIOG national representatives.

INTRODUCTION: The Sustainable Development Goals of the United Nations include a commitment to "leave no one behind" as a universal goal. To achieve this in geriatric oncology (GO) worldwide, it is important to understand the current state of GO at an international level. The International Society of Geriatric Oncology (SIOG) has several National Representatives (NRs) who act as SIOG's delegates in their respective countries. The NRs took part in this international survey exploring the state of GO practice, identifying barriers and solutions. MATERIALS AND METHODS: The NRs answered open-ended questions by email from February 2020 to October 2022. The questionnaire domains included the demographic information of older adults for their countries, and the NRs' opinions on whether GO is developing, what the barriers are to developing GO, and proposed actions to remove these barriers. The demographic data of each country reported in the survey was adjusted using literature and database searches. RESULTS: Twenty-one of thirty countries with NRs (70%) participated in this questionnaire study: 12 European, four Asian, two North American, two South American, and one Oceanian. The proportion of the population aged ≥75 years varied from 2.2% to 15.8%, and the average life expectancy also varied from 70 years to 86 years. All NRs reported that GO was developing in their country; four NRs (18%) reported that GO was well developed. Although all NRs agreed that geriatric assessment was useful, only three reported that it was used day-to-day in their countries' clinical practice (14%). The major barriers identified were the lack of (i) evidence to support GO use, (ii) awareness and interest in GO, and (iii) resources (time, manpower, and funding). The major proposed actions were to (i) provide new evidence through clinical trials specific for GO patients, (ii) stimulate awareness through networking, and (iii) deliver educational materials and information to healthcare providers and medical students. DISCUSSION: This current survey has identified the barriers to GO and proposed actions that could remove them. Broader awareness seems to be essential to implementing GO. Additional actions are needed to develop GO within countries and can be supported through international partnerships.

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

INTRODUCTION: 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). MATERIALS AND METHODS: 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. DISCUSSION: 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.

Quality of life in patients with cancer during the COVID-19 pandemic - a Danish cross-sectional study (COPICADS).

BACKGROUND: The COVID-19 pandemic is an international public health crisis. The risk of getting an infection with COVID-19 might impact the emotional well-being in patients with cancer. The aim of this study was to investigate quality of life (QoL) for patients with cancer during the COVID-19 pandemic. PATIENTS AND METHODS: A cross-sectional survey, including questions about demographics, concerns of COVID-19 impact on cancer treatment and outpatient clinic visits, and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire was sent to patients with cancer at the Department of Oncology, Odense University Hospital, Denmark. The survey was open from 15th May to 29th May 2020, and 4.571 responded. Results were compared to the Danish 'Barometer Study' conducted by the Danish Cancer Society to elucidate experiences with the Danish healthcare system prior to COVID-19 pandemic. RESULTS: In total, 9% of patients with cancer had refrained from consulting a doctor or the hospital due to fear of COVID-19 infection, and 80% were concerned about contracting COVID-19 to some extent. Seventeen patients were tested positive for COVID-19. The mean global QoL and emotional functioning (EF) scores were 71.3 and 82.8, respectively. In comparison to the 'Barometer Study', no clinical significant differences in QoL and EF scores were observed. Multivariate analysis demonstrated that being 'Concerned about contracting corona-virus' was correlated with lower QoL and EF scores. Factors associated with being concerned of contracting COVID-19 were comorbid conditions, incurable cancer, receiving medical cancer treatment and female gender. CONCLUSION: Danish patients with cancer during the COVID-19 pandemic did not have lower scores of QoL and emotional functioning compared to the Danish 'Barometer Study'. However, the study suggests that concerns of contracting COVID-19 was correlated with lower scores of QoL.

Efficacy and safety of immune checkpoint inhibitors in a Danish real life non-small cell lung cancer population: a retrospective cohort study.

Background: To investigate effect and toxicity of immune checkpoint inhibition (ICI) in a Danish real-life non-small cell lung cancer (NSCLC) population. By including patients underrepresented in clinical trials, such as those with brain metastasis (BM), higher age, more comorbidity and poorer performance status (ECOG), comparison of unselected patients to clinical trial populations is possible. Material and methods: Real life data were gathered from 118 consecutive NSCLC patients with incurable NSCLC treated with ICI at the Department of Oncology at the University Hospital of Odense, Denmark from September 2015 to April 2018. Immune-related adverse events (irAEs) grades 3-5 were registered prospectively during the same period. Additional patient related data were obtained retrospectively from patients' files. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier estimates, the log-rank test and cox regression analysis performed for factors affecting survival. Results: Median age for patients was 66 years (IQR 59-71) and 62 years (range: 55-64) for those with BM. Females 63%; adenocarcinoma (AC)/squamous/others 69%/23%/8%; ECOG ≥ 2 10%; bone/brain/liver metastases 36%/18%/15%; PD-L1 (TPS) <1%/ ≥ 1%/ ≤ 49%/ ≥ 50%/NR: 3%/14%/68%/15%; baseline autoimmunity 10%, Charlson's Comorbidity Index Score (CCIS) ≥ 2 39%, treatment line: 1st/2nd/ ≥ 3rd 39%/30%/31%. Median OS for patients receiving ICI in ≥2 line was 11.5 months versus not reached in first line (HR 2.6, [95% CI: 1.3-5.0], p = .005). For patients with BM, the median OS was 8.2 months (HR 1.38, [95% CI: 0.7-2.5], p = .37). Twenty-four percent of patients terminated ICI due to irAE grades 3-5 alone (grade 5, n = 1), which were not associated with higher age or BM. Conclusions: OS and PFS were comparable to clinical trial reports. Long-lasting remission is also possible in patients with BM. Real-life populations have higher rates of irAE grades 3 and 4 than reported in clinical trials, but it does not seem to impact median OS.

Long-term use of metformin and colorectal cancer risk in type II diabetics: a population-based case-control study.

In vitro and animal studies indicate that metformin prevents colorectal cancer (CRC). Epidemiological studies, however, have been equivocal. We undertook this study to assess whether metformin prevents CRC in individuals with type II diabetes. We performed a nested case-control study restricted to Danish citizens with type II diabetes. Data were collected from four Danish nationwide registries. Cases were type II diabetics with a primary CRC between 2000 and 2009, and controls were sampled among subjects with type II diabetes. Long-term exposure to metformin was defined by the redeeming of prescriptions for a cumulative dose of 2000 g within 5 years prior to the index date. To control for potential confounders, we used unconditional logistic regression. We generated adjusted odds ratios (OR) for the association between metformin and CRC and performed subanalyses for selected subgroups and for the dose-response relation. We identified 2088 cases and 9060 controls during the study period. The association between long-term metformin use and CRC gave an adjusted OR at 0.83 (95% CI 0.68-1.00). A protective effect on CRC with long-term use of metformin was only evident for women (OR 0.66 vs. 0.99 for men). There was a significant dose-response association of metformin use >250 defined daily dose (DDD) and for the duration of metformin use >1 year. We found an indication of a protective effect of long-term metformin use against CRC in type II diabetics, although this effect was only seen in women.

Bevacizumab in combination with cetuximab and irinotecan after failure of cetuximab and irinotecan in patients with metastatic colorectal cancer.

BACKGROUND: The efficacy and safety of concurrent administration of irinotecan with the two monoclonal antibodies cetuximab and bevacizumab as fourth line therapy in heavily pretreated patients with metastatic colorectal cancer were evaluated. PATIENTS AND METHODS: Patients with metastatic colorectal cancer who had progressed on therapy with 5-FU, oxaliplatin and irinotecan in the first and second line setting and on the combination of irinotecan and cetuximab in third line setting independent of their KRAS mutation status, were treated with irinotecan and cetuximab combined with bevacizumab in a dosage of 5 mg/kg. All drugs were administered every second week. RESULTS: From January 2007 to November 2008 27 patients were treated with cetuximab, irinotecan and bevacizumab. The triple-combination was well tolerated. Progression free survival (PFS) was 8.3 months and median overall survival (mOS) was 12.0 months. Two patients without KRAS mutation (7%) obtained a partial response and 17 (63%) had stable disease for at least two months. A retrospective KRAS mutation analysis revealed that there was a trend toward longer PFS and mOS in patients without KRAS mutations compared to patients with KRAS mutations with a PFS of 8.9 vs. 5.1 months and a mOS of 12.7 vs. 9.0 months. CONCLUSION: Bevacizumab is safe to add to irinotecan and cetuximab with a toxicity profile that seems to be similar to what would be expected from the agents alone. The results indicate that adding bevacizumab to irinotecan and cetuximab in a fourth line setting may induce a high rate of disease control in heavily pretreated patients with metastatic colorectal cancer.