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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.

Roughly 50% of cancer cases occur in people aged 65 years or older. Older people are often diagnosed at a later stage and might receive less (intensive) treatment, which might affect the outcome. In addition, an older age might be associated with biological differences in tumour and microenvironment behaviour, a domain that has been poorly studied so far. In this narrative Review of published literature, we explored the reported differences in tumour biology according to age in five major cancer types: breast, colorectal, prostate, lung, and melanoma. Our literature search uncovered clear differences in tumour histology and subtype distribution in older people compared with younger patients, as well as age-specific patterns of tumour mutations and other molecular alterations. Several studies also indicate notable changes in tumour-infiltrating immune cells in tumours of older versus younger people, although this research is still in its infancy. More research is needed and might lead to a better understandingof the biology of ageing in relation to malignancy. This knowledge could provide new perspectives for more personalised cancer treatments, eventually improving the global outcomes of older patients with cancer, Roughly 50% of cancer cases occur in people aged 65 years or older. Older people are often diagnosed at a later stage and might receive less (intensive) treatment, which might affect the outcome. In addition, an older age might be associated with biological differences in tumour and microenvironment behaviour, a domain that has been poorly studied so far. In this narrative Review of published literature, we explored the reported differences in tumour biology according to age in five major cancer types: breast, colorectal, prostate, lung, and melanoma. Our literature search uncovered clear differences in tumour histology and subtype distribution in older people compared with younger patients, as well as age-specific patterns of tumour mutations and other molecular alterations. Several studies also indicate notable changes in tumour-infiltrating immune cells in tumours of older versus younger people, although this research is still in its infancy. More research is needed and might lead to a better understandingof the biology of ageing in relation to malignancy. This knowledge could provide new perspectives for more personalised cancer treatments, eventually improving the global outcomes of older patients with cancer.

Background The combination of CDK4/6 inhibitors and endocrine therapy is the current standard first-line therapy for patients with HR+/HER2- metastatic breast cancer (mBC). Preliminary data suggest that CDK4/6 inhibitors not only induce tumor response by blocking CDK-dependent cell growth but that they can also alter the host immune function and stimulate tumor cell-directed immunity. However, clinical data are scarce, and no data exist about the impact of age and frailty, which are known to impact host immunity (immunosenescence). Materials and methods This prospective ongoing study is evaluating the efficacy and toxicity of the CDK4/6 inhibitor ribociclib and letrozole in older (≥ 70 years) patients with HR+/HER2- mBC (RIBOB, NCT03956654). In the associated blood biomarker sub-study, we investigate the impact of ribociclib and letrozole on the immune subset composition. Immune cell subsets were analyzed using flowcytometry (BD FACSVerse™) of peripheral blood mononuclear cells isolated at baseline (before ribociclib administration) and after three months of ribociclib treatment. In total, six multicolor flow cytometry staining panels were set up to investigate the changes in the immune cell subsets (CD4+ T-cell subsets, CD8+ T-cell subsets, general immune cell subsets, T-regulatory cell subsets, T-cell activation status subsets, and myeloid-derived suppressor cells subsets). Frailty status was assessed at baseline using the G8 screening tool (range score: 0-17) as a proxy. The paired t-test and matched-pairs Wilcoxon signed-rank test are used to evaluate changes in immune subset composition between baseline and after three months. The unpaired t-test and Mann-Whitney U test are used to evaluate differences in immune subset composition between frail and fit patients. Results Immune cell subset distribution and evolution were available for 15 older patients (median age: 77 yrs.; IQR 74-83), 4 considered fit (G8-score >14), and 11 frail (G8-score ≤14). Firstly, we analyzed the difference in immune subset composition between baseline and three months for the whole cohort. There was a significant increase of naïve T-regulatory cells (p=0.0012) and a significant increase in CD8+ T-cell activation indicated by an upregulation of HLA-DR+ (p=0.0055) and CD38+ (p=0.0203). Secondly, the difference in immune subset composition between fit and frail persons was assessed showing a lower activation status of CD4+ and CD8+ T-cell subsets in frail persons at baseline, as assessed by several activation markers: CD4+PD1+ (p=0.0051), CD4+PD1+CD69+ (p=0.0013), CD8+PD1+ (p=0.0073), and CD8+PD1+CD69+ (p=0.0339). These significant differences between fit and frail disappeared after three months, largely because of increased T-cell activation in the frail subset. Conclusion Ribociclib plus letrozole treatment for three months results in an upregulation of the T-regulatory cells’ naïve subset, suggesting an expansion of the T-cell repertoire, which is compatible with immune cell activation. Furthermore, the activation status of the CD8+ T-cells was upregulated. These observations confirm recent findings reported by Scirocchi F. et al. (Lancet, 2022). In addition, frail older patients show a lower baseline T-cell activation status compared to fit older patients but seem to have increased T-cell activation after treatment exposure. In the future, correlations with treatment response will be evaluated when follow-up data matures. Our data encourage the further assessment of immune cell modulation in combination with CDK4/6 inhibitors in the treatment of patients with metastatic breast cancer. Citation Format: Yentl Lambrechts, Sigrid Hatse, Cindy Kenis, Lore Decoster, Evandro de Azambuja, Guy Jerusalem, Patrick Neven, Lissandra Dal Lago, Hannelore Denys, Peter Vuylsteke, Frank Cornelis, Kevin Punie, Giuseppe Floris, Christine Desmedt, Annouschka Laenen, Noam Pondé, Hans Wildiers. Ribociclib plus letrozole alters the immune subset composition in older (≥70 yrs.) patients with HR+/HER2- metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-29.

BackgroundBSMO 2014-01 is a published prospective phase 2 study investigating neoadjuvant weekly paclitaxel and carboplatin, followed by epirubicin and cyclophosphamide in 63 patients with triple-negative breast cancer. Pathological complete response (pCR) was observed in 54%. A secondary endpoint of the study was to correlate pCR rate to the presence of germline pathogenic variants in DNA damage response (DDR) genes or in core genes involved in Homologous Recombination (HR).MethodsPeripheral blood from 60 patients was collected for germline DNA analysis. Whole Exome Sequencing was performed; only rare variants (minor allelic frequency < 0.01) in 276 DDR genes were considered. The correlation between pCR rate and DDR or HR deficiency was analyzed using the Fisher's exact test. The same was done for the correlation between DDR gene mutations and the presence of hematologic toxicities. ResultsThirty-five out of 60 patients (58.3%) carried a protein disrupting germline mutation in a DDR gene. Twenty-four of these 35 patients (68.6%) had a pCR, while a pCR was observed in 40% without a DDR mutation (p=0.026). In 14/15 patients (93.3%) with a HR core gene mutation a pCR was obtained, while a pCR was present in 44.4% without a HR core gene mutation (p=0.0007). Eight of nine patients (88.9%) with a BRCA1 or BRCA2 pathogenic variant reached a pCR compared to 51% of the BRCA wild-type patients (p=0.035). ConclusionsThis is the first study to demonstrate that germline pathogenic variants in genes involved in HR core genes predicts for pCR after platinum-containing neoadjuvant chemotherapy.

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.

Background: BSMO 2014-01 is a published prospective phase 2 study evaluating the efficacy of neoadjuvant EC and PC in the treatment of TNBC patients. (1) The addition of weekly carboplatin to neoadjuvant paclitaxel and dose-dense EC lead to a pathologic complete response (pCR) of 54%, comparable to prior studies. A secondary endpoint was to correlate pCR to homologous recombination (HR) and DNA damaging repair (DDR) deficiency due to germline mutations. Methods: Sixty-three patients (pts) of which nine already identified with a BRCA 1/2 mutation were considered. Peripheral blood was collected in 52 pts after obtaining informed consent for a broad genomic DNA analysis. Whole Exome Sequencing was performed, and only rare variants (M.A.F. Citation Format: Christel Fontaine, Vincent Renard, Heidi Van den Bulck, Peter Vuylsteke, Philippe Glorieux, Catherine Dopchie, Lore Decoster, Ahmad Awada, Hans Wildiers, Sylvie De Brakeleer, Erik Teugels, Jacques De Grève. Evaluation of germline whole exome sequencing of early breast cancer patients with triple negative breast cancer (TNBC) included in a prospective study of neoadjuvant chemotherapy (NAC) with epirubicin and cyclophosphamide (EC) and carboplatin-paclitaxel (PC) (BSMO 2014-01) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-05.

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 GroupPerformance 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.

Medical writing and editorial assistance were provided by Tim Ibbotson, PhD, of ApotheCom (Yardley, PA, USA) and funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Statistical analysis was done by Herbert Thijs, Sofie Van Waes, and Filip Deforce (DICE). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. The authors thanks to Hermine Leroi for the operational support and assistance during this project. The authors thank Katrien Willaert for the initiation of the study and its study design.

BACKGROUND: The objective of this study was to evaluate if 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)-derived parameters are useful in predicting response and survival after programmed cell death protein 1 (PD-1) blocking immunotherapy in patients with advanced NSCLC characterized by a high programmed death-ligand 1 (PD-L1) expression (≥50%) on immunohistochemistry. PATIENTS AND METHODS: In 30 patients with advanced stage IV non-small-cell lung cancer (NSCLC) and high PD-L1 expression, 18F-FDG PET/CT parameters before start of treatment with PD-1 blocking immunotherapy were evaluated retrospectively. In 24 out of the 30 patients, 18F-FDG PET/CT was available 8 to 9 weeks after start of the treatment. Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and metabolic responses assessed on 18F-FDG PET/CT were compared. RESULTS: Median follow-up was 20 months (range, 4.2-37.6). Median PD-L1 expression was 80%. The objective response rate with RECIST 1.1 was 53.3%. Median progression-free survival (PFS) was 12.4 months (95% confidence interval [CI], 1.0-37.8), and median overall survival (OS) was 14.9 months (95% CI, 2.4-38.2). Baseline 18F-FDG PET/CT parameters did not differ between responders and non-responders (all P > .05). The maximum standardized uptake value (SUVmax) was the only 18F-FDG PET/CT parameter associated with PFS (P = .04), with a trend for OS (P = .06). At first evaluation, response according to total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) were associated with PFS and OS (both P < .0001). This was not the case for RECIST 1.1 (P = .29 for PFS and P = .38 for OS). CONCLUSION: Clinical response and survival were independent from metabolic tumor volume at baseline. Reduction of metabolic tumor volume after 8 to 9 weeks of treatment was a better predictor for prolonged survival than RECIST 1.1.

Background The median age of prostate cancer diagnosis is 66 years, and the median age of men who die of the disease is eighty years. The public health impact of prostate cancer is already substantial and, given the rapidly ageing world population, can only increase. In this context, the International Society of Geriatric Oncology (SIOG) Task Forces have, since 2010, been developing guidelines for the management of senior adults with prostate cancer. Material and methods Since prostate cancer and geriatric oncology are both rapidly evolving fields, a new multidisciplinary Task Force was formed in 2018 to update SIOG recommendations, principally on health status screening tools and treatment. The task force reviewed pertinent articles published between June 2016 and June 2018 and abstracts from European Association of Urology (EAU), European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO) and American Society of Clinical Oncology Genito-urinary (ASCO GU) meetings over the same period, using search terms relevant to prostate cancer, the elderly, geriatric evaluation, local treatments and advanced disease. Each member of the group proposed modifications to the previous guidelines. These were collated and circulated. The final manuscript reflects the expert consensus. Results The 2019 consensus is that men aged 75 years and older with prostate cancer should be managed according to their individual health status, and not according to age. Based on available rapid health screening tools, geriatric evaluation and geriatric interventions, the Task Force recommends that patients are classified according to health status into three groups: (1) ‘healthy’ or ‘fit’ patients should have the same treatment options as younger patients; (2) ‘vulnerable’ patients are candidates for geriatric interventions which—if successful—may make it appropriate for them to receive standard treatment and (3) ‘frail’ patients with major impairments who should receive adapted or palliative treatment. The 2019 SIOG Task Force recommendations also discuss prospects and unmet needs for health status evaluation in everyday practice in older patients with prostate cancer.

Tumor infiltrating lymphocytes (TIL), programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) expression are important prognostic markers. This study aimed to investigate these markers in lung adenocarcinoma (ADC) biopsies from patients with stage IIIB or IV ADC with little or no smoking history, to investigate their prognostic value and to correlate these results with the presence of driver mutations in the tumors. TIL were retrospectively evaluated on hematoxylin and eosin stained slides from 152 tumor samples. PD-1/PD-L1 expression was retrospectively evaluated with PD-1/PD-L1 immunohistochemistry (IHC) double staining on 74 tumor samples with sufficient residual tissue. PD-L1 expression was analysed on stromal cells of the tumor compartment, the tumor cells and TIL and PD-1 on TIL. Median overall survival (OS) was longer in patients with high stromal TIL infiltration compared to patients with low stromal TIL infiltration (68 weeks vs. 35 weeks respectively; p = 0.003). This was observed most prominently in KRAS mutant tumors (95 weeks vs. 12 weeks; p = 0.003). Only PD-L1 expression on tumor stromal cells influenced OS and indicated a worse prognosis (77 weeks vs 25 weeks; p = 0.013). Stromal TIL counts nor PD-1/PD-L1 expression levels were associated with the presence of driver mutations. The results of the current study reinforce the prognostic role of TIL in lung ADC, which is most prominent in KRAS mutant cancers. The results of the PD-1/PD-L1 analysis suggest that stromal cells can effectively suppress the anti-tumor immune response via the PD-L1 pathway.

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.

PURPOSE: Using the EORTC Global Health Status (GHS) scale, we aimed to determine minimal clinically important differences (MCID) in health-related quality of life (HRQOL) changes for older cancer patients with a geriatric risk profile, as defined by the geriatric 8 (G8) health screening tool, undergoing treatment. Simultaneously, we assessed baseline patient characteristics prognostic for HRQOL changes. METHODS: Our analysis included 1424 (G8 ≤ 14) older patients with cancer scheduled to receive chemotherapy (n = 683) or surgery (n = 741). Anchor-based methods, linking the GHS score to clinical indicators, were used to determine MCID between baseline and follow-up at 3 months. A threshold of 0.2 standard deviation (SD) was used to exclude MCID estimates too small for interpretation. Logistic regressions analysed baseline patient characteristics prognostic for HRQOL changes. RESULTS: The 15-item Geriatric Depression Scale (GDS15), Visual Analogue Scale (VAS) for Fatigue and ECOG Performance Status (PS) were selected as clinical anchors. In the surgery group, MCID estimates for improvement and deterioration were ECOG PS (5*, 11*), GDS15 (5*, 2) and VAS Fatigue (3, 9*). In the chemotherapy group, MCID estimates for improvement and deterioration were ECOG PS (8*, 7*), GDS15 (5, 4) and VAS Fatigue (5, 5*). Estimates with * were > 0.2 SD threshold. Patients experiencing pain or malnutrition (surgery group) or fatigue (chemotherapy group) at baseline showed a significantly stable or improved HRQOL (p

BACKGROUND: This study aims to investigate the occurrence of unplanned hospitalizations in older patients with cancer and to determine predictive factors. METHODS: A prospective Belgian multicentre (n = 22), observational cohort study was performed. Patients ≥70 years with a malignant tumor were included. Patients underwent G8 screening followed by geriatric assessment (GA) if abnormal at baseline and were followed for unplanned hospitalizations at approximately three months. Uni- and multivariable regression models were performed to determine predictive factors associated with unplanned hospitalizations in older patients with an abnormal G8. RESULTS: In total, 7763 patients were included in the current analysis of which 2409 (31%) patients with a normal G8 score and 5354 (69%) with an abnormal G8 score. Patients with an abnormal G8 were hospitalized more frequently than patients with a normal G8 (22.9% versus 12.4%; p

Purpose of review This review highlights the latest development in the use of geriatric assessment(GA) and frailty assessment for older adults with cancer. Recent findings From 2019, there were six large randomized controlled trials (RCTs) completed of GA for older adults with cancer, as well as several studies of frailty screening tools. Summary The findings in this review highlight the benefits of implementing GA, followed by interventions to address the identified issues (GA -guided interventions). Four of six RCTs that implemented GA for older adults with cancer showed positive impact on various outcomes, including treatment toxicity and quality of life. GA implementation varied significantly between studies, from oncologist acting on GA summary, geriatrician comanagement, to full GA by a multidisciplinary team. However, there were several barriers reported to implementing GA for all older adults with cancer, such as access to geriatrics and resource issues. Future research needs to elucidate how to best operationalize GA in various cancer settings. The authors also reviewed frailty screening tools and latest evidence on their use and impact.

The objective of this study was to evaluate ifIn 30 patients with advanced stage IV non-small-cell lung cancer (NSCLC) and high PD-L1 expression,Median follow-up was 20 months (range, 4.2-37.6). Median PD-L1 expression was 80%. The objective response rate with RECIST 1.1 was 53.3%. Median progression-free survival (PFS) was 12.4 months (95% confidence interval [CI], 1.0-37.8), and median overall survival (OS) was 14.9 months (95% CI, 2.4-38.2). BaselineClinical response and survival were independent from metabolic tumor volume at baseline. Reduction of metabolic tumor volume after 8 to 9 weeks of treatment was a better predictor for prolonged survival than RECIST 1.1.

Objectives To compare real life effectiveness and safety of nivolumab in patients with non-small cell lung cancer (NSCLC), according to age and Eastern Cooperative Group performance status (ECOG-PS). Methods We performed a retrospective analysis of patients treated with nivolumab for NSCLC within a Belgian compassionate use program from July 2015 until December 2016. Safety and effectiveness were compared between patients aged ≥70 years and

Advanced cancers are associated with a chronic inflammation, especially high interleukin-6 (IL-6) and with various levels of adipokines (leptin and adiponectin), while ghrelin counteracts the anorexigenic effect of leptin in cancer-induced anorexia-cachexia syndrome. We aimed to understand how IL-6, adipokines and ghrelin plasma levels could be influenced by cancer on the one hand, and by age, frailty, and nutritional status in old cancer patients on the other hand. Ninety-nine patients aged 79[76–83] years old were included. Sixty-six percent had advanced stages of cancer, and 34% had cachexia. Fifty percent were at risk of malnutrition, and 10% had overt malnutrition. None of the variables studied was significantly correlated with the advanced stage, or cachexia. In multiple regression, the only parameter significantly and positively associated with age was adiponectin (p = 0.008). Despite a high prevalence of frailty in our study, we did not find any independent association of frailty (assessed by G8) with IL-6, leptin, adiponectin, or ghrelin in multivariate analysis. We observed that a low albumin level was independently associated with a higher level of IL-6 (p < 0.0001), but not with the MNA score. However, leptin showed a positive correlation with BMI (p < 0.0001), confirming the persistence of a relationship between leptin and adiposity, even in older cancer patients. Finally, high IL-6 level was associated with a higher mortality rate (p = 0.027). In conclusion, IL-6, leptin, adiponectin, and ghrelin are not associated with advanced stages of cancer or cancer-induced cachexia in older subjects with cancer, but they are significantly correlated with anthropometric factors and body composition., SCOPUS: ar.j, info:eu-repo/semantics/published

Objectives: We aimed to determine the prognostic value of baseline Health-Related Quality Of Life (HRQOL) and geriatric assessment (GA) to predict three-month mortality in older patients with cancer undergoing treatment. Methods: Logistic regressions analysed HRQOL, as measured with the EORTC Global Health Status (GHS) scale, and geriatric information prognostic for early mortality controlling for oncology variables. The assessment was established with the odds ratio (OR), 95% confidence interval (CI) and level of significance set at p < 0.05. Discriminative power was evaluated with area under the curve (AUC). Results: In total, 6769 patients were included in the study, of whom 1259 (18.60%) died at three months. Our model showed higher odds of early death for patients with lower HRQOL (GHS, OR 0.98, 95% CI 0.98-0.99; p < 0.001), a geriatric risk profile (G8 Screening Tool, 1.94, 1.14-3.29; p = 0.014), cognitive decline (Mini Mental State Examination, 1.41, 1.15-1.72; p 0.001), being at risk for malnutrition (Mini Nutritional Assessment-Short Form, 1.54, 1.21-1.98; p = 0.001), fatigue (Visual Analogue Scale for Fatigue, 1.45, 1.16-1.82; p = 0.012) and comorbidities (Charlson Comorbidity index, 1.23, 1.02-1.49: p = 0.033). Additionally, older age, poor ECOG PS and being male increased the odds of early death, although the magnitude differed depending on tumor site and stage, and treatment (all p < 0.05). Predictive accuracy increased with 3.7% when including HRQOL and GA in the model. Conclusion: The results suggest that, in addition to traditional clinical measures, HRQOL and GA provide additional prognostic information for early death, but the odds differ by patient and tumor characteristics. (C) 2020 Elsevier Ltd. All rights reserved.

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.

Dacomitinib is a second-generation, irreversible EGFR tyrosine kinase inhibitor. We compared its efficacy and safety with that of the reversible EGFR tyrosine kinase inhibitor gefitinib in the first-line treatment of patients with advanced EGFR-mutation-positive non-small-cell lung cancer (NSCLC).In this international, multicentre, randomised, open-label, phase 3 study (ARCHER 1050), we enrolled adults (aged ≥18 years or ≥20 years in Japan and South Korea) with newly diagnosed advanced NSCLC and one EGFR mutation (exon 19 deletion or Leu858Arg) at 71 academic medical centres and university hospitals in seven countries or special administrative regions. We randomly assigned participants (1:1) to receive oral dacomitinib 45 mg/day (in 28-day cycles) or oral gefitinib 250 mg/day (in 28-day cycles) until disease progression or another discontinuation criterion was met. Randomisation, stratified by race and EGFR mutation type, was done with a computer-generated random code assigned by a central interactive web response system. The primary endpoint was progression-free survival assessed by masked independent review in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT01774721, and is ongoing but no longer recruiting patients.Between May 9, 2013, and March 20, 2015, 452 eligible patients were randomly assigned to receive dacomitinib (n=227) or gefitinib (n=225). Median duration of follow-up for progression-free survival was 22·1 months (95% CI 20·3-23·9). Median progression-free survival according to masked independent review was 14·7 months (95% CI 11·1-16·6) in the dacomitinib group and 9·2 months (9·1-11·0) in the gefitinib group (hazard ratio 0·59, 95% CI 0·47-0·74; p0·0001). The most common grade 3-4 adverse events were dermatitis acneiform (31 [14%] of 227 patients given dacomitinib vs none of 224 patients given gefitinib), diarrhoea (19 [8%] vs two [1%]), and raised alanine aminotransferase levels (two [1%] vs 19 [8%]). Treatment-related serious adverse events were reported in 21 (9%) patients given dacomitinib and in ten (4%) patients given gefitinib. Two treatment-related deaths occurred in the dacomitinib group (one related to untreated diarrhoea and one to untreated cholelithases/liver disease) and one in the gefitinib group (related to sigmoid colon diverticulitis/rupture complicated by pneumonia).Dacomitinib significantly improved progression-free survival over gefitinib in first-line treatment of patients with EGFR-mutation-positive NSCLC and should be considered as a new treatment option for this population.SFJ Pharmaceuticals Group and Pfizer.

Introduction: Overall prognosis of early TNBC remains inferior to that of other breast cancer subtypes. Neoadjuvant platinum added to taxanes-anthracycline regimen has been reported to potentially improve pathologic complete response (pCR) and survival in TNBC pts. Aim: To report the final results of the efficacy and toxicity of the addition of weekly Cp to P and dose dense (dd) EC on the pCR rate in an open-label phase II study in stage II/III TNBC pts. Patients and methods: In the BSMO study sixty three pts received dd P (80mg/m2/wk) concurrent with Cp (AUC=2) for 12 weeks, added to bi-weekly E (90mg/m2) and C (600mg/m2) for 4 cycles, followed by surgery and radiotherapy. The primary endpoint was pCR in the breast and axilla. Additionally actual drug dosing and toxicities were registered. A correlative assessment of germline mutations in HRD genes is ongoing. Pts were monitored for clinical response by magnetic resonance and mammography, and also for relapse free survival and time to treatment failure. The study sample size has been calculated according to the optimal Simon's two-stage design method. The target sample size was 63 patients with 80% power to detect a pCR rate of > or=47% (α= 0.05). Results: Sixty three eligible pts with operable, non-inflammatory stage II/III TNBC were included. Most pts were between 40 and 59 yrs old and had clinical stage II disease. Forty percent were clinically node + and 68% were G3. Seventy three percent received breast conserving surgery. Sixty percent (38 out of 63 pts) achieved a pCR breast/axilla. Sixteen percent (10pts) missed three or more doses of wP, whereas at least 1 EC cycle was skipped in 19% (12pts). Sixty five percent had G3/4 neutropenia. Investigator reported febrile neutropenia occurred in 18 pts (28.5%) of which more than eighty percent during the EC part despite primary prophylaxis. Thrombocytopenia G3/4 was noticed in 10 pts (16%). Only four pts (6%) developed grade 3 peripheral neuropathy. Conclusion: The addition of weekly carboplatinum to neoadjuvant paclitaxel and ddEC is feasible and a pCR rate in the breast and axilla as high as 60% compares nicely with the results achieved with the similar 3 weekly carboplatinum arm of the CALBG 40603 trial. Febrile neutropenia rate was higher than the 3-weekly carboplatin arm in CALGB40603 trial, but occurred mainly during the EC part, while other toxicities are comparable. Future research could focus on this combination in the reverse sequence (first ECdd), which may lead to a better global haematological profile. Citation Format: Fontaine C, Cappoen N, Renard V, Van Den Bulck H, Vuylsteke P, Glorieux P, Dopchie C, Decoster L, De Grève J, Awada A, Wildiers H. Final results of weekly (w) neoadjuvant carboplatin (Cp) added to paclitaxel (P) followed by epirubicin (E) and cyclophosphamide (C) in triple negative breast cancer (TNBC) patients (pts): A BSMO breast cancer task force phase II study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-09.

Gastric (G) and gastro-esophageal junction (GEJ) adenocarcinomas are of the most common and deadly cancers worldwide and affect mainly patients over 70 years at diagnosis. Older age has been associated in gastric cancers with distal tumour location, well-differentiated adenocarcinoma and microsatellite instability and is not identified itself as an independent prognostic factor. As immune checkpoint inhibitors recently changed the landmark of advanced G and GEJ adenocarcinomas treatment, we decided to perform a literature review to define the evidence-level of clinical data in older patients. This work underlined the lasting low -inclusion rate of older patients and -implementation rate of frailty screening tools in clinical trials in G/GEJ carcinomas. In the first-line metastatic setting, two prospective randomized phase III studies have specifically assessed the efficacy of chemotherapy in older patients with HER2-negative gastric cancers, demonstrating the feasibility of reduced dose oxaliplatin-based chemotherapy regimen in this population. Only few data are available in HER2-positive tumors, or in the second-line setting. Furthermore, no specific trial with immune checkpoint inhibitors was performed in older frail patients whereas their benefit/adverse events ratio make them attractive candidates in this patient's population. We conclude that older fit patients can be treated in the same way as younger ones and included in clinical trials. Improving the outcome of older frail patients should be the oncology community next focus by implementing targeted interventions before initiating cancer therapy and designing specific clinical trials. Frailty screening tools and geriatric data collection have to be implemented in routine-practice and clinical trials. ispartof: CANCER TREATMENT REVIEWS vol:100 ispartof: location:Netherlands status: published

Introduction This study aims to evaluate the relevance of geriatric assessment (GA) in older patients with colorectal cancer (CRC) and to study functional status (FS) and chemotherapy-related toxicity during treatment. Methods Patients with CRC aged ≥ 70 years were evaluated at baseline using a GA. Results were communicated to the treating physician. At 2 to 3 months follow-up, FS was reassessed, and chemotherapy-related toxicity was recorded. Results A total of 193 patients, with a median age of 77 years, were included. GA was abnormal in 75% and revealed unknown problems in 40%. Treatment was altered in 37% based on clinical assessment. GA led to geriatric interventions in 9 patients (5%) and additionally influenced treatment in 1 patient. At follow-up (n = 164), functional decline was observed in 29 patients (18%) for activities of daily living (ADL) and in 60 patients (37%) for instrumental activities of daily living (IADL). Baseline IADL, depression, fatigue, and cognition were predictors for ADL decline, whereas no predictors for IADL decline could be identified. In the 109 patients receiving chemotherapy, stage and baseline fatigue were predictive for grade 3/4 hematologic toxicity, and baseline ADL, fatigue, and nutrition were predictive for grade 3/4 nonhematologic toxicity. Conclusion Although GA identified previously unknown problems in more than one-third of older CRC patients, the impact on interventions or treatment decisions was limited. Baseline GA parameters may predict functional decline and chemotherapy-related toxicity. Education of physicians treating older patients with CRC is an essential step in the implementation of GA and subsequent interventions.

PURPOSE: Older patients with lung cancer are a heterogeneous population making treatment decisions complex. This study aims to evaluate the value of geriatric assessment (GA) as well as the evolution of functional status (FS) in older patients with lung cancer, and to identify predictors associated with functional decline and overall survival (OS). METHODS: At baseline, GA was performed in patients ≥70 years with newly diagnosed lung cancer. FS measured by activities of daily living (ADL) and instrumental activities of daily living (IADL) was reassessed at follow-up to define functional decline and OS was collected. Predictors for functional decline and OS were determined. RESULTS: Two hundred and forty-five patients were included in this study. At baseline, GA deficiencies were present in all domains and ADL and IADL were impaired in 51 and 63% of patients, respectively. At follow-up, functional decline in ADL was observed in 23% and in IADL in 45% of patients. In multivariable analysis, radiotherapy was predictive for ADL decline. No other predictors for ADL or IADL decline were identified. Stage and baseline performance status were predictive for OS. CONCLUSIONS: Older patients with lung cancer present with multiple deficiencies covering all geriatric domains. During treatment, functional decline is observed in almost half of the patients. None of the specific domains of the GA were predictive for functional decline or survival, probably because of the high impact of the aggressiveness of this tumor type leading to a poor prognosis.

OBJECTIVES: This study aims to evaluate the evolution of functional status (FS) 2 to 3months after initiation of chemotherapy, to identify factors associated with functional decline during chemotherapy treatment and to investigate the prognostic value of functional decline for overall survival (OS). PATIENTS AND METHODS: Patients ≥70years with a malignant tumor were included when chemotherapy was initiated. All patients underwent a geriatric assessment (GA) including FS measured by Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL). FS of patients was followed by repeating ADL and IADL to identify functional decline. RESULTS: From 10/2009 until 07/2011, 439 patients were included. At follow-up, ADL and IADL data were available for 387 patients. Functional decline in ADL and IADL was observed in 19.9% and 41.3% of the patients respectively. In multivariable logistic regression analysis, baseline factors associated with decline in ADL are abnormal nutritional status (OR:2.02) and IADL dependency (OR:1.76). Oncological setting (disease progression/relapse vs new diagnosis) (OR:0.59) is the only determinant of decline in IADL. Functional decline in ADL is strongly prognostic for OS (logrank p-value

Objective To better define the rare adverse event (AE) of diabetes mellitus associated with immune checkpoint inhibitors (ICIs). Design and methods We report the case of a lung cancer patient with diabetic ketoacidosis (DKA) and autoimmune thyroiditis during pembrolizumab treatment. We provide a systematic review of all published cases (PubMed/Web of Science/Cochrane, through November 2018) of autoimmune diabetes mellitus related to blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4)-, programmed cell death 1 (PD-1) receptor or its ligand (PD-L1) or combination (ICI) therapy. Results Our literature search identified 90 patient cases (our case excluded). Most patients were treated with anti-PD-1 or anti-PD-L1 as monotherapy (79%) or in combination with CTLA-4 blockade (15%). On average, diabetes mellitus was diagnosed after 4.5 cycles; earlier for combination ICI at 2.7 cycles. Early-onset diabetes mellitus (after one or two cycles) was observed during all treatment regimens. Diabetic ketoacidosis was present in 71%, while elevated lipase levels were detected in 52% (13/25). Islet autoantibodies were positive in 53% of patients with a predominance of glutamic acid decarboxylase antibodies. Susceptible HLA genotypes were present in 65% (mostly DR4). Thyroid dysfunction was the most frequent other endocrine AE at 24% incidence in this patient population. Conclusion ICI-related diabetes mellitus is a rare but often life-threatening metabolic urgency of which health-care professionals and patients should be aware. Close monitoring of blood glucose and prompt endocrine investigation in case of hyperglycemia is advisable. Predisposing factors such as HLA genotype might explain why some individuals are at risk.

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. ispartof: INTERNATIONAL JOURNAL OF CANCER vol:146 issue:11 pages:3207-3218 ispartof: location:United States status: published

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.

TPS2066 Background: Better knowledge on the evolving epidemiology and biology of CNS metastases are key elements for the development of new treatment strategies and identification of promising therapeutic targets. A multidisciplinary Brain Metastases Clinical Research Platform called BrainStorm was launched by the Jules Bordet Institute and the Oncodistinct network. The BrainStorm program includes mainly patients with non-CNS metastatic solid tumors with high risk of developing CNS metastases allowing to build a large database focusing on three time periods: before the diagnosis of CNS metastases (Part A), at diagnosis (Part B) and after the diagnosis of CNS metastases (Part C). Methods: Subjects with newly diagnosed non-CNS metastases or up to 24 months from diagnosis of non-CNS metastases from triple-negative and HER2-positive breast cancer, lung cancer and melanoma are eligible for part A of the program. Subjects presenting with a 1st CNS event and not yet enrolled (previously mentioned cohorts and a cohort of other tumor types) can enter directly in parts B and subsequently part C of the study. Eligible subjects are followed for 48 months for relevant clinical data, neurological examinations, quality of life, survival status, and undergo examinations and samplings (Table 1). A total of 280 subjects (40 per cohort) with a 1st CNS event will be enrolled. The main objectives of the program are to collect clinical and biological data with the aim to identify risk factors for CNS metastases development (Part A) and to better understand the biology of CNS metastases (brain and leptomeningeal –Parts B and C) aiming to discover new targets for therapy and intensify the multidisciplinary approach for the management of CNS metastases from solid tumors. The translational part of the program will evaluate among others the use of cerebrospinal fluid circulating tumor DNA (CSF-ctDNA) as a surrogate for CNS metastases in order to characterize its molecular landscape. Currently, the study is recruiting in several sites within the Oncodistinct network. The data collected will help to develop innovative multidisciplinary research projects that could be implemented in all parts of the BrainStorm program. Clinical trial information: NCT04109131. [Table: see text]

// Amir Noeparast 1 , Erik Teugels 1 , Philippe Giron 1 , Gil Verschelden 1 , Sylvia De Brakeleer 1 , Lore Decoster 1 , Jacques De Greve 1 1 Laboratory of Molecular Oncology and Department of Medical Oncology, Oncologisch Centrum, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium Correspondence to: Jacques De Greve, email: jacques.degreve@uzbrussel.be Keywords: non-V600 BRAF, lung cancer, impaired-kinase, Trametinib, Dabrafenib Received: October 08, 2015 Accepted: June 09, 2016 Published: August 26, 2016 ABSTRACT Approximately half of BRAF-mutated Non-small cell lung cancers (NSCLCs) harbor a non-V600 BRAF mutation, accounting for ~40,000 annual deaths worldwide. Recent studies have revealed the benefits of combined targeted therapy with a RAF-inhibitor (Dabrafenib) and a MEK-inhibitor (Trametinib) in treating V600 BRAF mutant cancers, including NSCLC. In contrast, sensitivity of non-V600 BRAF mutations to these inhibitors is not documented. Non-V600 mutations can either increase or impair BRAF kinase activity. However, impaired BRAF kinases can still activate the ERK pathway in a CRAF-dependent manner. Herein, beyond describing a cohort of BRAF mutant NSCLC patients and functionally analyzing 13 tumor-derived BRAF mutations, we demonstrate that both types of non-V600 BRAF mutations can be sensitive to clinically relevant doses of Dabrafenib and Trametinib in HEK293T cells, in lung epithelial cellular model (BEAS-2B) and in human cancer cell lines harboring non-V600 BRAF mutations. ERK activity induced by both types of these mutations is further reduced by combinatorial drug treatment. Moreover, the combination leads to more prolonged ERK inhibition and has anti-proliferative and pro-apoptotic effects in cells harboring both types of non-V600 BRAF mutations. This study provides a basis for the clinical exploration of non-V600 BRAF mutant lung cancers upon treatment with Trametinib and Dabrafenib.

BACKGROUND: In the general older population, geriatric assessment (GA)-guided treatment plans can improve overall survival, quality of life and functional status (FS). In GA-related research in geriatric oncology, studies mainly focused on geriatric screening and GA but not on geriatric recommendations, interventions and follow-up. The aim of this study was to investigate the adherence to geriatric recommendations and subsequent actions undertaken in older patients with cancer. PATIENT AND METHODS: A prospective Belgian multicenter (N = 22) cohort study included patients ≥70 years with a malignant tumor upon oncologic treatment decision. Patients with an abnormal result on the geriatric screening (G8 ≤14/17) underwent GA. Geriatric recommendations were formulated based on GA results. At follow-up the adherence to geriatric recommendations was documented including a description of actions undertaken. RESULTS: From November 2012 till February 2015, G8 screening was carried out in 8451 patients, of which 5838 patients had an abnormal result. Geriatric recommendations data were available for 5631 patients. Geriatric recommendations were made for 4459 patients. Geriatric interventions data were available for 4167 patients. A total of 12 384 geriatric recommendations were made. At least one different geriatric recommendation was implemented in 2874 patients. A dietician, social worker and geriatrician intervened most frequently for problems detected on the nutritional, social and functional domain. A total of 7569 actions were undertaken for a total of 5725 geriatric interventions, most frequently nutritional support and supplements, extended home care and psychological support. CONCLUSIONS: This large-scale Belgian study focuses on the adherence to geriatric recommendations and subsequent actions undertaken and contributes to the optimal management of older patients with cancer. We identified the domains for which geriatric recommendations are most frequently made and adhered to, and which referrals to other health care workers and facilities are frequently applied in the multidisciplinary approach of older patients with cancer. ispartof: ANNALS OF ONCOLOGY vol:29 issue:9 pages:1987-1994 ispartof: location:England status: published

With a median age of 70 years at diagnosis, lung cancer is a disease of older persons. As a consequence oncologists are confronted with an increasing older lung cancer population for which treatment decisions are needed. In the past years, the therapeutic landscape of advanced non-small cell lung cancer (NSCLC) has changed impressively with the introduction of targeted therapies and immunotherapy next to chemotherapy. Treatment choices for advanced NSCLC are mainly guided by different tumor-related characteristics. However, in older patients treatment decisions are more complex because of the scarcity of data from large randomized studies in older patients and the heterogeneity of this population with regards to different geriatric domains such as functional status, comorbidity and polypharmacy. The present manuscript reviews available data for the different treatment options for older patients with NSCLC as well as the use of geriatric assessment as an evaluation and guidance tool.

Introduction: AI’s are the preferred adjuvant hormonal treatment for postmenopausal(PM) estrogen receptor positive (ER+) disease because of the improved efficacy over tamoxifen in terms of disease free survival and reduction in distant recurrence. AI’s have been associated with increased bone loss by blocking peripheral tissue estrogen synthesis, arthralgia and a negative effect on lipid metabolism. In this prospective study we wanted to assess the amount of bone loss and the changes in lipid levels in early breast cancer(EBC) patients (pts) treated with 3yrs of extended letrozole as part of the SOLE study after 5 yrs of adjuvant AI. Objectives: the primary objective of the study is to calculate the mean percentage change in bone mineral density(BMD)(g/cm2) after 8 yrs of letrozole and to compare between the continuous(C) and intermittent(I) intake of letrozole. The secondary objectives are to correlate the mean change in BMD with the initial value, BMI and to describe the evolution of the lipid levels in both groups. Patients and methods: BMD was measured at the lumbar spine (L2-4) and hip by dual energy X-ray absorptiometry (DEXA) in PM pts. with ER+ EBC. We also measured the fasting lipid levels baseline and after 8 yrs of an AI. Differences between the two groups were assessed by the independent samples T-test and the correlation by the linear regression analysis. Results: Fifty four pts were included in the study with a mean age of 62.5 yrs(+/-8.6 yrs). Seventeen pts are too early to be evaluable, 8 pts stopped letrozole due to adverse events and 2 pts had no baseline DEXA values. Two pts received tamoxifen 2 to 5 yrs before inclusion in the SOLE study. The remaining 25 pts showed a mean change in BMD for the lumbar spine of -1.1 (10.6SD) and for the hip -4.4 (7.04SD). Currently 13 pts in the C arm demonstrated a mean decrease in BMD for the (LS) of -2.7(10.2SD), and for the hip of -2.7(5.5SD). Twelve pts included in the I arm experienced a mean increase in BMD for the LS of 0.65(SD11.2) and a mean decrease in BMD for the hip of -4.9(9.1SD). The difference between the two treatment groups was not significant for the LS measurements after 8yrs (p=0.4) nor for the hip (p=0.23) neither was it at baseline (p=0.9; 0.1). Only three pts had fractures due to trauma. The overall fracture rate was only 0.05%.There was no correlation with the BMI, but there was a significant correlation with baseline BMD.(p=0.002)The mean fasting cholesterol levels at 8yrs in the C arm was 214mg/dl(41.3SD) and in the I arm was 218mg/dl(35.6SD)and was not significantly different(p=0.8), nor was it at baseline(p=0.5). Conclusion: This first prospective long term BMD and lipid follow-up study in PM EBC pts taking adjuvant letrozole beyond 5 yrs shows a decline in BMD. Until now no significant differences were observed between continuous and intermittent letrozole. An updated and detailed follow-up on more patients will be presented. Citation Format: Christel Fontaine, Lore Decoster, Denis Schallier, Leen Vanacker, Jacques De Grève, Marian Vanhoeij, Guy Verfaillie, Jan Lamote. Prospective study of aromatase inhibitor-induced bone loss and lipid levels in early hormone sensitive breast cancer treated with AI during 8 years [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-11.