A randomized phase II clinical trial of stereotactic body radiation therapy (SBRT) and systemic pembrolizumab with or without intratumoral avelumab/ipilimumab plus CD1c (BDCA-1)+/CD141 (BDCA-3)+ myeloid dendritic cells in solid tumors.

BACKGROUND: Radiotherapy (RT) synergizes with immune checkpoint blockade (ICB). CD1c(BDCA-1)+/CD141(BDCA-3)+ myeloid dendritic cells (myDC) in the tumor microenvironment are indispensable at initiating effector T-cell responses and response to ICB. METHODS: In this phase II clinical trial, anti-PD-1 ICB pretreated oligometastatic patients (tumor agnostic) underwent a leukapheresis followed by isolation of CD1c(BDCA-1)+/CD141(BDCA-3)+ myDC. Following hypofractionated stereotactic body RT (3 × 8 Gy), patients were randomized (3:1). Respectively, in arm A (immediate treatment), intratumoral (IT) ipilimumab (10 mg) and avelumab (40 mg) combined with intravenous (IV) pembrolizumab (200 mg) were administered followed by IT injection of myDC; subsequently, IV pembrolizumab and IT ipilimumab/avelumab were continued (q3W). In arm B (contemporary control arm), patients received IV pembrolizumab, with possibility to cross-over at progression. Primary endpoint was 1-year progression-free survival rate (PFS). Secondary endpoints were safety, feasibility, objective response rate, PFS, and overall survival (OS). RESULTS: Thirteen patients (10 in arm A, eight non-small cell lung cancer, and five melanoma) were enrolled. Two patients crossed over. One-year PFS rate was 10% in arm A and 0% in arm B. Two patients in arm A obtained a partial response, and one patient obtained a stable disease as best response. In arm B, one patient obtained a SD. Median PFS and OS were 21.8 weeks (arm A) versus 24.9 (arm B), and 62.7 versus 57.9 weeks, respectively. An iatrogenic pneumothorax was the only grade 3 treatment-related adverse event. CONCLUSION: SBRT and pembrolizumab with or without IT avelumab/ipilimumab and IT myDC in oligometastatic patients are safe and feasible with a clinically meaningful tumor response rate. However, the study failed to reach its primary endpoint. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT04571632 (09 AUG 2020). EUDRACT: 2019-003668-32. Date of registration: 17 DEC 2019, amendment 1: 6 MAR 2021, amendment 2: 4 FEB 2022.

Incidence of falls and fall-related injuries and their predictive factors in frail older persons with cancer: a multicenter study.

BACKGROUND: Falls and fall-related injuries are a major public health problem. Data on falls in older persons with cancer is limited and robust data on falls within those with a frailty profile are missing. The aim of this study is to investigate the incidence and predictive factors for falls and fall-related injuries in frail older persons with cancer. METHODS: This study is a secondary data analysis from data previously collected in a large prospective multicenter observational cohort study in older persons with cancer in 22 Belgian hospitals (November 2012-February 2015). Patients ≥70 years with a malignant tumor and a frailty profile based on an abnormal G8 score were included upon treatment decision and evaluated with a Geriatric Assessment (GA). At follow-up, data on falls and fall-related injuries were documented. RESULTS: At baseline 2141 (37.2%) of 5759 included patients reported at least one fall in the past 12 months, 1427 patients (66.7%) sustained an injury. Fall-related data of 3681 patients were available at follow-up and at least one fall was reported by 769 patients (20.9%) at follow-up, of whom 289 (37.6%) fell more than once and a fall-related injury was reported by 484 patients (62.9%). Fear of falling was reported in 47.4% of the patients at baseline and in 55.6% of the patients at follow-up. In multivariable analysis, sex and falls history in the past 12 months were predictive factors for both falls and fall-related injuries at follow-up. Other predictive factors for falls, were risk for depression, cognitive impairment, dependency in activities of daily living, fear of falling, and use of professional home care. CONCLUSION: Given the high number of falls and fall-related injuries and high prevalence of fear of falling, multifactorial falls risk assessment and management programs should be integrated in the care of frail older persons with cancer. Further studies with long-term follow-up, subsequent impact on cancer treatment and interventions for fall prevention, and integration of other important topics like medication and circumstances of a fall, are warranted. TRIAL REGISTRATION: B322201215495.

The genomic landscape of nonsmall cell lung carcinoma in never smokers.

Lung cancer is the number one cause of cancer-related death worldwide with cigarette smoking as its major risk factor. Although the incidence of lung cancer in never smokers is rising, this subgroup of patients is underrepresented in genomic studies of lung cancer. Here, we assembled a prospective cohort of 46 never-smoking, nonsmall cell lung cancer (NSCLC) patients and performed whole-exome and low-coverage whole-genome sequencing on tumors and matched germline DNA. We observed fewer somatic mutations, genomic breakpoints and a smaller fraction of the genome with chromosomal instability in lung tumors from never smokers compared to smokers. The lower number of mutations, enabled us to identify TSC22D1 as a potential driver gene in NSCLC. On the other hand, the frequency of mutations in actionable genes such as EGFR and ERBB2 and of amplifications in MET were higher, while the mutation rate of TP53, which is a negative prognostic factor, was lower in never smokers compared to smokers. Together, these observations suggest a more favorable prognosis for never smokers with NSCLC. Classification of somatic mutations into six-substitution type patterns or into 96-substitution type signatures revealed distinct clusters between smokers and never smokers. Particularly, we identified in never smokers signatures related to aging, homologous recombination damage and APOBEC/AID activity as the most important underlying processes of NSCLC. This further indicates that second-hand smoking is not driving NSCLC pathogenesis in never smokers.

Weekly carboplatin plus neoadjuvant anthracycline-taxane-based regimen in early triple-negative breast cancer: a prospective phase II trial by the Breast Cancer Task Force of the Belgian Society of Medical Oncology (BSMO).

AIM: To evaluate the pCR rate and toxicity of the addition of weekly carboplatin (Cp) to paclitaxel (wP) and dose-dense (dd) epirubicin/cyclophosphamide (EC) in an open-label phase II study in TNBC patients. METHODS: Patients were included if they had stage II and III TNBC and received wP (80 mg/m2/week) concurrent with weekly Cp (AUC = 2) for 12 weeks, followed by bi-weekly epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) plus granulocyte colony-stimulating factor (G-CSF) for four cycles, followed by surgery. The primary endpoint was the rate of pCR [(ypT0/isypN0)]. Secondary endpoints included safety and drug delivery. RESULTS: Sixty-three eligible patients were included. Median age was 51 years (range 29-74); 88.9% had stage II disease, 46% were clinically node positive, and 77.8% had grade 3 tumors. Fifty-four percent achieved a pCR. Twelve percent missed two or more doses of wP, whereas at least two cycles of EC were missed in 9.5%. The rate of tolerance without delays or dose reductions is very low (16%). Sixty-two percent had G3/4 neutropenia. Febrile neutropenia occurred in 18 patients of which more than eighty percent occurred during EC despite primary prophylaxis with G-CSF. Thrombocytopenia grade 3/4 was noticed in 11 pts. Three patients developed grade 3 peripheral neuropathy. CONCLUSION: The addition of weekly carboplatin to neoadjuvant paclitaxel and dd EC leads to a pCR rate comparable to prior studies (54%). However, hematological toxicity and febrile neutropenia rate was unexpectedly high. Future investigations could focus on reversing the sequence, which may lead to better hematological tolerability.

Retrospective comparison of two consecutive cohorts of adjuvant chemotherapy regimens of cyclophosphamide with either docetaxel or paclitaxel in older patients with early breast cancer.

Adjuvant chemotherapy with docetaxel/cyclophosphamide (TC) is adopted worldwide as a valuable option for elderly patients with high-risk early breast cancer. Some studies suggest that paclitaxel may have a better therapeutic ratio than docetaxel. Therefore we have implemented an adjuvant chemotherapy in which docetaxel was replaced by paclitaxel. We report here the retrospective analysis of that cohort and make a safety comparison with an earlier TC cohort in the same target population. This retrospective analysis demonstrates the feasibility of paclitaxel/cyclophosphamide as an alternative, better tolerated adjuvant regimen for elderly patients. Further evaluation and assessment of noninferiority to TC is warranted.

The prognostic value of 3 commonly measured blood parameters and geriatric assessment to predict overall survival in addition to clinical information in older patients with cancer.

BACKGROUND: The current study was performed to evaluate the prognostic value of laboratory parameters and geriatric assessment (GA) in addition to a baseline model with clinical information regarding overall survival (OS) in patients with cancer. METHODS: GA was systematically performed in patients aged ≥70 years. The baseline model consisted of age, tumor type, and stage of disease. The incremental prognostic values of the GA as a whole (10-item GA) and laboratory parameters were assessed separately and combined. The parameters included hemoglobin (Hb), albumin, C-reactive protein (CRP), and the Glasgow Prognostic Score (GPS). Analyses were conducted with continuous and dichotomized variables. Cox models were compared based on Akaike information criterion (ΔAIC) and their discriminatory ability was assessed using the concordance probability estimate (CPE). RESULTS: A total of 328 patients were considered for this analysis. The baseline model had a CPE of 0.725. The addition of CRP, albumin, and Hb combined resulted in the best performing model (ΔAIC: 40.12 and CPE: 0.757) among the laboratory parameters. However, the 10-item GA improved the baseline model even more (ΔAIC: 46.03 and CPE: 0.769). Similar results were observed in the analysis with dichotomous variables. The addition of the 3 laboratory parameters (CRP, albumin, and Hb) improved the CPE by 1.4% compared with the baseline model already extended with the 10-item GA. The CPE increase (1.7%) was the highest with the GPS in the analysis with dichotomous variables. CONCLUSIONS: GA appears to add slightly more prognostic information than laboratory parameters in addition to clinical information. The laboratory parameters have an additional prognostic value beyond clinical and geriatric information.

The added value of geriatric screening and assessment for predicting overall survival in older patients with cancer.

BACKGROUND: The aim of this study was to determine and compare the added prognostic value of screening tools, geriatric assessment (GA) components, and GA summaries to clinical information for overall survival (OS) in older patients with cancer. METHODS: A screening and a 10-item GA were systematically performed in patients ≥70 years old with cancer. Cox regression analyses were conducted to evaluate the added prognostic value for OS of screening tools, GA, and GA summaries to clinical information (age, stage, and tumor type) in 2 cohorts (A and B). Cox models were compared on the basis of the Akaike information criterion and the concordance probability estimate. The 2 cohorts for the analyses were similar but independent. RESULTS: A complete case analysis was available for 763 patients (median age, 76 years) in cohort A and for 402 patients (median age, 77 years) in cohort B. In both cohorts, most individual GA components were independent prognostic factors for OS. Nutritional status (assessed with the Mini Nutritional Assessment Short Form) and functional status (assessed with the Instrumental Activities of Daily Living) consistently displayed a strong capacity to predict OS. Less consistent results were found for screening tools. GA summaries performed the best in comparison with the screening tools and the individual GA components. CONCLUSIONS: Most individual GA components, especially nutritional status and functional status, are prognostic factors for OS in older patients with cancer. GA summaries provide more prognostic information than individual GA components but only moderately improve the prognostic baseline model with clinical information.

Shifts in subsets of CD8+ T-cells as evidence of immunosenescence in patients with cancers affecting the lungs: an observational case-control study.

BACKGROUND: Shifts in CD8+ T-cell subsets that are hallmarks of immunosenescence are observed in ageing and in conditions of chronic immune stimulation. Presently, there is limited documentation of such changes in lung cancer and other malignancies affecting the lungs. METHODS: Changes in CD8+ T-cell subsets, based on the expression of CD28 and CD57, were analysed in patients with various forms of cancer affecting the lungs, undergoing chemotherapy and in a control group over six months, using multi-colour flow cytometry. RESULTS: The differences between patients and controls, and the changes in the frequency of CD8+ T-cell subpopulations among lung cancer patients corresponded to those seen in immunosenescence: lower CD8-/CD8+ ratio, lower proportions of CD28+CD57- cells consisting of naïve and central memory cells, and higher proportions of senescent-enriched CD28-CD57+ cells among the lung cancer patients, with the stage IV lung cancer patients showing the most pronounced changes. Also observed was a tendency of chemotherapy to induce the formation of CD28+CD57+ cells, which, in line with the capacity of chemotherapy to induce the formation of senescent cells, might provide more evidence supporting CD28+CD57+ cells as senescent cells. CONCLUSION: Immunosenescence was present before the start of the treatment; it appeared to be pronounced in patients with advanced cases of malignancies affecting the lungs, and might not be averted by chemotherapy.

Fall predictors in older cancer patients: a multicenter prospective study.

BACKGROUND: In the older population falls are a common problem and a major cause of morbidity, mortality and functional decline. The etiology is often multifactorial making the identification of fall predictors essential for preventive measures. Despite this knowledge, data on falls within the older cancer population are limited. The objective of this study was to evaluate the occurrence of falls within 2 to 3 months after cancer treatment decision and to identify predictors of falls (≥1 fall) during follow-up. METHODS: Older patients (70 years or more) with a cancer treatment decision were included. At baseline, all patients underwent geriatric screening (G8 and Flemish Triage Risk Screening Tool), followed by a geriatric assessment including living situation, activities of daily living (ADL), instrumental activities of daily living (IADL), fall history in the past 12 months, fatigue, cognition, depression, nutrition, comorbidities and polypharmacy. Questionnaires were used to collect follow-up (2-3 months) data. Univariate and multivariate analyses were performed to identify predictors for falls (≥1 fall) during follow-up. RESULTS: At baseline, 295 (31.5%) of 937 included patients reported at least one fall in the past 12 months with 88 patients (29.5%) sustaining a major injury. During follow-up (2-3 months), 142 (17.6%) patients fell, of whom 51.4% fell recurrently and 17.6% reported a major injury. Baseline fall history in the past 12 months (OR = 3.926), fatigue (OR = 0.380), ADL dependency (OR = 0.492), geriatric risk profile by G8 (OR = 0.471) and living alone (OR = 1.631) were independent predictors of falls (≥1 fall) within 2-3 months after cancer treatment decision. CONCLUSION: Falls are a serious problem among older cancer patients. Geriatric screening and assessment data can identify patients at risk for a fall. A patient with risk factors associated with falls should undergo further evaluation and intervention to prevent potentially injurious fall incidents.

Recommended Physiotherapy Modalities for Oncology Patients with Palliative Needs and Its Influence on Patient-Reported Outcome Measures: A Systematic Review.

BACKGROUND: This review aims to explore the role of physiotherapy in early and traditional palliative care (PC) for oncology patients, focusing on its impact on six patient-reported outcomes (PROMs), namely fatigue, pain, cachexia, quality of life (QoL), physical functioning (PHF), and psychosocial functioning (PSF). The purpose is to assess the effectiveness of various physiotherapy interventions and identify gaps in the current research to understand their potential benefits in PC better. METHODS: A systematic literature search was conducted across PubMed, Embase, and Web of Science, concluding on 21 December 2023. Two independent reviewers screened the articles for inclusion. The Cochrane Risk of Bias Tool 2 was employed to assess the risk of bias, while the GRADE approach was used to evaluate the certainty of the evidence. RESULTS: Nine randomized controlled trials (RCTs) were included, with most showing a high risk of bias, particularly in outcome measurement and missing data. Cognitive behavioral therapy (CBT) was the only intervention that significantly reduced fatigue, enhanced PHF, and improved QoL and emotional functioning. Graded exercise therapy (GET) did not yield significant results. Combined interventions, such as education with problem-solving or nutritional counseling with physical activity, showed no significant effects. Massage significantly improved QoL and reduced pain, while physical application therapies were effective in pain reduction. Mindful breathing exercises (MBE) improved QoL but had a non-significant impact on appetite. The overall certainty of the evidence was low. CONCLUSIONS: Physiotherapy can positively influence PROMs in oncology PC; however, the low quality and high risk of bias in existing studies highlight the need for more rigorous research to confirm these findings and guide clinical practice.

The crosstalk between lung cancer and the bone marrow niche fuels emergency myelopoiesis.

Modest response rates to immunotherapy observed in advanced lung cancer patients underscore the need to identify reliable biomarkers and targets, enhancing both treatment decision-making and efficacy. Factors such as PD-L1 expression, tumor mutation burden, and a 'hot' tumor microenvironment with heightened effector T cell infiltration have consistently been associated with positive responses. In contrast, the predictive role of the abundantly present tumor-infiltrating myeloid cell (TIMs) fraction remains somewhat uncertain, partly explained by their towering variety in terms of ontogeny, phenotype, location, and function. Nevertheless, numerous preclinical and clinical studies established a clear link between lung cancer progression and alterations in intra- and extramedullary hematopoiesis, leading to emergency myelopoiesis at the expense of megakaryocyte/erythroid and lymphoid differentiation. These observations affirm that a continuous crosstalk between solid cancers such as lung cancer and the bone marrow niche (BMN) must take place. However, the BMN, encompassing hematopoietic stem and progenitor cells, differentiated immune and stromal cells, remains inadequately explored in solid cancer patients. Subsequently, no clear consensus has been reached on the exact breadth of tumor installed hematopoiesis perturbing cues nor their predictive power for immunotherapy. As the current era of single-cell omics is reshaping our understanding of the hematopoietic process and the subcluster landscape of lung TIMs, we aim to present an updated overview of the hierarchical differentiation process of TIMs within the BMN of solid cancer bearing subjects. Our comprehensive overview underscores that lung cancer should be regarded as a systemic disease in which the cues governing the lung tumor-BMN crosstalk might bolster the definition of new biomarkers and druggable targets, potentially mitigating the high attrition rate of leading immunotherapies for NSCLC.

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.

Phase I Study of [68Ga]Ga-Anti-CD206-sdAb for PET/CT Assessment of Protumorigenic Macrophage Presence in Solid Tumors (MMR Phase I).

Macrophages play an important role throughout the body. Antiinflammatory macrophages expressing the macrophage mannose receptor (MMR, CD206) are involved in disease development, ranging from oncology to atherosclerosis and rheumatoid arthritis. [68Ga]Ga-NOTA-anti-CD206 single-domain antibody (sdAb) is a PET tracer targeting CD206. This first-in-human study, as its primary objective, evaluated the safety, biodistribution, and dosimetry of this tracer. The secondary objective was to assess its tumor uptake. Methods: Seven patients with a solid tumor of at least 10 mm, an Eastern Cooperative Oncology Group score of 0 or 1, and good renal and hepatic function were included. Safety was evaluated using clinical examination and blood sampling before and after injection. For biodistribution and dosimetry, PET/CT was performed at 11, 90, and 150 min after injection; organs showing tracer uptake were delineated, and dosimetry was evaluated. Blood samples were obtained at selected time points for blood clearance. Metabolites in blood and urine were assessed. Results: Seven patients were injected with, on average, 191 MBq of [68Ga]Ga-NOTA-anti-CD206-sdAb. Only 1 transient adverse event of mild severity was considered to be possibly, although unlikely, related to the study drug (headache, Common Terminology Criteria for Adverse Events grade 1). The blood clearance was fast, with less than 20% of the injected activity remaining after 80 min. There was uptake in the liver, kidneys, spleen, adrenals, and red bone marrow. The average effective dose from the radiopharmaceutical was 4.2 mSv for males and 5.2 mSv for females. No metabolites were detected. Preliminary data of tumor uptake in cancer lesions showed higher uptake in the 3 patients who subsequently progressed than in the 3 patients without progression. One patient could not be evaluated because of technical failure. Conclusion: [68Ga]Ga-NOTA-anti-CD206-sdAb is safe and well tolerated. It shows rapid blood clearance and renal excretion, enabling high contrast-to-noise imaging at 90 min after injection. The radiation dose is comparable to that of routinely used PET tracers. These findings and the preliminary results in cancer patients warrant further investigation of this tracer in phase II clinical trials.

Linking clinical and population-based data in older patients with cancer in Belgium: Feasibility and clinical outcomes.

INTRODUCTION: Geriatric screening and geriatric assessment (GS/GA) have proven their benefits in the care for older patients with cancer. However, less is known about the predictive value of GS/GA for outcomes. To research this, clinical data on GS/GA can be enriched with population-based data. In this article we describe the methods and feasibility of data linkage, and first clinical outcomes (GS/GA results and overall survival). MATERIALS AND METHODS: A large cohort study consisting of patients aged ≥70 years with a new cancer diagnosis was established using linked data from clinical and population-based databases. Clinical data were derived from a previous prospective study where older patients with cancer were screened with G8, followed by GA in case of an abnormal result (GS/GA study; 2009-2015). These data were linked to cancer registration data from the Belgian Cancer Registry (BCR), reimbursement data of the health insurance companies (InterMutualistic Agency, IMA), and hospital discharge data (Technical Cell, TCT). Cox regression analyses were conducted to evaluate the prognostic value of the G8 geriatric screening tool. RESULTS: Of the 8067 eligible patients with a new cancer diagnosis, linkage of data from the GS/GA study and data from the BCR was successful for 93.7%, resulting in a cohort of 7556 patients available for the current analysis. Further linkage with the IMA and TCT database resulted in a cohort of 7314 patients (96.8%). Based on G8 geriatric screening, 67.9% of the patients had a geriatric risk profile. Malnutrition and functional dependence were the most common GA-identified risk factors. An abnormal baseline G8 score (≤14/17) was associated with lower overall survival (adjusted HR [aHR] = 1.62 [1.50-1.75], p < 0.001). DISCUSSION: Linking clinical and population-based databases for older patients with cancer has shown to be feasible. The GS/GA results at cancer diagnosis demonstrate the vulnerability of this population and the G8 score showed prognostic value for overall survival. The established cohort of almost 8000 patients with long-term follow-up will serve as a basis in the future for detailed analyses on long-term outcomes beyond survival.

End-of-Life Care in the Last Three Months before Death in Older Patients with Cancer in Belgium: A Large Retrospective Cohort Study Using Data Linkage.

This study aims to describe end-of-life (EOL) care in older patients with cancer and investigate the association between geriatric assessment (GA) results and specialized palliative care (SPC) use. Older patients with a new cancer diagnosis (2009-2015) originally included in a previous multicentric study were selected if they died before the end of follow-up (2019). At the time of cancer diagnosis, patients underwent geriatric screening with Geriatric 8 (G8) followed by GA in case of a G8 score ≤14/17. These data were linked to the cancer registry and healthcare reimbursement data for follow-up. EOL care was assessed in the last three months before death, and associations were analyzed using logistic regression. A total of 3546 deceased older patients with cancer with a median age of 79 years at diagnosis were included. Breast, colon, and lung cancer were the most common diagnoses. In the last three months of life, 76.3% were hospitalized, 49.1% had an emergency department visit, and 43.5% received SPC. In total, 55.0% died in the hospital (38.5% in a non-palliative care unit and 16.4% in a palliative care unit). In multivariable analyses, functional and cognitive impairment at cancer diagnosis was associated with less SPC. Further research on optimizing EOL healthcare utilization and broadening access to SPC is needed.

Long-term health-care utilisation in older patients with cancer and the association with the Geriatric 8 screening tool: a retrospective analysis using linked clinical and population-based data in Belgium.

BACKGROUND: Little evidence is available on the long-term health-care utilisation of older patients with cancer and whether this is associated with geriatric screening results. We aimed to evaluate long-term health-care utilisation among older patients after cancer diagnosis and the association with baseline Geriatric 8 (G8) screening results. METHODS: For this retrospective analysis, we included data from three cohort studies for patients (aged ≥70 years) with a new cancer diagnosis who underwent G8 screening between Oct 19, 2009 and Feb 27, 2015, and who survived more than 3 months after G8 screening. The clinical data were linked to cancer registry and health-care reimbursement data for long-term follow-up. The occurrence of outcomes (inpatient hospital admissions, emergency department visits, use of intensive care, contacts with general practitioner [GP], contacts with a specialist, use of home care, and nursing home admissions) was assessed in the 3 years after G8 screening. We assessed the association between outcomes and baseline G8 score (normal score [>14] or abnormal [≤14]) using adjusted rate ratios (aRRs) calculated from Poisson regression and using cumulative incidence calculated as a time-to-event analysis with the Kaplan-Meier method. FINDINGS: 7556 patients had a new cancer diagnosis, of whom 6391 patients (median age 77 years [IQR 74-82]) met inclusion criteria and were included. 4110 (64·3%) of 6391 patients had an abnormal baseline G8 score (≤14 of 17 points). In the first 3 months after G8 screening, health-care utilisation peaked and then decreased over time, with the exception of GP contacts and home care days, which remained high throughout the 3-year follow-up period. Compared with patients with a normal baseline G8 score, patients with an abnormal baseline G8 score had more hospital admissions (aRR 1·20 [95% CI 1·15-1·25]; p<0·0001), hospital days (1·66 [1·64-1·68]; p<0·0001), emergency department visits (1·42 [1·34-1·52]; p<0·0001), intensive care days (1·49 [1·39-1·60]; p<0·0001), general practitioner contacts (1·19 [1·17-1·20]; p<0·0001), home care days (1·59 [1·58-1·60]; p<0·0001), and nursing home admissions (16·7% vs 3·1%; p<0·0001) in the 3-year follow-up period. At 3 years, of the 2281 patients with a normal baseline G8 score, 1421 (62·3%) continued to live at home independently and 503 (22·0%) had died. Of the 4110 patients with an abnormal baseline G8 score, 1057 (25·7%) continued to live at home independently and 2191 (53·3%) had died. INTERPRETATION: An abnormal G8 score at cancer diagnosis was associated with increased health-care utilisation in the subsequent 3 years among patients who survived longer than 3 months. FUNDING: Stand up to Cancer, the Flemish Cancer Society.

Efficacy of a Flat Low Dose of Nivolumab in Advanced Cancer: A Retrospective Case Series.

BACKGROUND/AIM: Immunotherapy with PD-1/PDL1 blocking monoclonal antibodies has improved survival compared to the standard-of-care chemotherapy for several malignancies at different stages of these malignancies. Due to several reasons, many cancer patients in medical need have no access to these drugs. In this study, we aimed to investigate whether a low dose of nivolumab could also lead to a therapeutic response. PATIENTS AND METHODS: Patients with advanced cancer were treated with a flat low dose of 10 mg of nivolumab IV every two weeks at no drug cost. RESULTS: Disease control was noted in nine of the 18 patients. Two patients achieved complete remission, two had prolonged partial remission, and five had stable disease, of these only two experienced adverse events. CONCLUSION: A flat low dose of nivolumab may have clinical activity and is a cheap therapeutic option in patients in medical need for whom standard-dose immune checkpoint inhibitors are not accessible for any reason.

Functional status in older patients with cancer and a frailty risk profile: A multicenter observational study.

INTRODUCTION: Functional status (FS) and frailty are significant concerns for older adults, especially those with cancer. Data on FS (Activities of Daily Living [ADL]; Instrumental Activities of Daily Living [IADL]) and its evolution during cancer treatment in older patients and a frailty risk profile are scarce. Therefore, this study examines FS and its evolution in older patients with cancer and a frailty risk profile and investigates characteristics associated with functional decline. MATERIAL AND METHODS: This secondary data-analysis, focusing on FS, uses data from a large prospective multicenter observational cohort study. Patients ≥70 years with a solid tumor and a frailty risk profile based on the G8 screening tool (score ≤ 14) were included. A geriatric assessment was performed including evaluation of FS based on ADL and IADL. At approximately three months of follow-up, FS was reassessed. Univariable and multivariable logistic regression analyses were used to identify predictive factors for functional decline in ADL and IADL. RESULTS: Data on ADL and IADL were available at baseline and follow-up in 3388 patients. At baseline 1886 (55.7%) patients were dependent for ADL, whereas 2085 (61.5%) patients were dependent at follow-up. Functional decline was observed in 23.6% of patients. For IADL 2218 (65.5%) patients were dependent for IADL, whereas 2591 (76.5%) patients were dependent at follow-up. Functional decline in IADL was observed in 41.0% of patients. In multivariable analysis, disease stage III or IV, comorbidities, falls history in the past twelve months, and FS measured by IADL were predictive factors for functional decline in both ADL and IADL. Other predictive factors for functional decline in ADL were polypharmacy, Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) score 2-4, and cognitive impairment, and for functional decline in IADL were female sex, fatigue, and risk for depression. DISCUSSION: Functional impairments are frequent in older persons with cancer and a frailty risk profile, and several characteristics are identified that are significantly associated with functional decline. Therefore, FS is an essential part of the geriatric assessment which should be standard of care for this patient population. Next step is to proceed with directed interventions with the aim to limit the risk of functional decline as much as possible.