Associated Factors to Efficacy and Tolerance of Immunotherapy in Older Patients with Cancer Aged 70 Years and Over: Impact of Coprescriptions.

BACKGROUND: Immunotherapy with immune checkpoint blockers (ICB) significantly improves the prognosis for an increasing number of cancers. However, data on geriatric populations taking ICB are rare. OBJECTIVE: This study aimed to identify factors associated with the efficacy and tolerance of ICB in an older population. PATIENTS AND METHODS: This retrospective monocentric study included consecutive patients aged ≥ 70 years with solid cancer who received ICB between January 2018 and December 2019. Efficacy was assessed by progression-free survival (PFS) and tolerance was defined as cessation of immunotherapy due to the occurrence of any adverse event. RESULTS: One hundred and five patients (65.7% men) were included, mainly at the metastatic stage (95.2%); 50.5% had lung cancer. Most (80%) patients were treated with anti-PD1 (nivolumab, pembrolizumab), 19.1% with anti-PD-L1 (atezolizumab, durvalumab, and avelumab) and 0.9% with anti-CTLA4 ICB (ipilimumab). Median PFS was 3.7 months [95% confidence interval (CI) (2.75-5.70)]. PFS was shorter in univariate analysis when ICB was taken concomitantly with an antiplatelet agent (AP) [hazard ratio (HR) = 1.93; 95% CI (1.22-3.04); p = 0.005]. Tolerance was lower in univariate analysis for lung cancer [odds ratio (OR) = 3.03; 95% CI (1.07-8.56), p < 0.05] and in patients taking proton pump inhibitors (PPI) [OR = 5.50; 95% CI (1.96-15.42), p < 0.001]. There was a trend toward poorer tolerance among patients living alone [OR = 2.26; 95% CI (0.76-6.72); p = 0.14]. CONCLUSIONS: In older patients taking ICB for solid cancers, concomitant AP may influence efficacy and concomitant PPI may influence tolerance. Further studies are needed to confirm these results.

Quality of life and perceived burden of the primary caregiver of patients aged 70 and over with cancer 5 years after initial treatment.

PURPOSE: Long-term effects of being the primary caregiver of an older patient with cancer are not known. This study aimed to assess health-related quality of life (HRQoL) in primary caregivers of patients aged 70 and older with cancer, 5 years after initial treatment. Secondly, to compare the HRQoL between former primary caregivers whose caregiving relationship had ceased (primary caregiver no longer directly assisting the patient because of patient death or removal to another city or admission to an institution) and current caregivers, and to determine the perceived burden of the primary caregivers. METHODS: Prospective observational study including primary caregivers of patients aged 70 and older with cancer. HRQoL and perceived burden were assessed using the SF-12 and Zarit Burden Interview (ZBI) at baseline and 5 years after initial treatment. RESULTS: Ninety-six caregivers were initially included; at 5 years, 46 caregivers completed the SF-12 and ZBI between June 15 and October 26, 2020. Primary caregiver's HRQoL scores had significantly decreased over time for physical functioning (mean difference = -10, p=0.04), vitality (MD= -10.5, p=0.02), and role emotional (MD= -8.1, p=0.01) dimensions. The comparison at 5 years according to caregiving status showed no difference for all HRQoL dimensions. There was no decrease in perceived burden at 5 years. CONCLUSION: Some dimensions of HRQoL decreased at 5 years with a stable low perceived burden. TRIAL REGISTRATION: NCT04478903.

[Inappropriate admissions of Ehpad residents to emergency departments]. / Admissions inappropriées des résidents d'Ehpad aux urgences.

After a review of inappropriate admissions of residents of residential care facilities for the dependent elderly (Ehpad) to the emergency room, we propose ways to reduce them. They include giving the coordinating physician a clinical role, organizing continuity and permanence of care in all Ehpad, signing agreements between Ehpad and hospital for direct hospitalization and collaboration with mobile teams and geriatric hotlines, generalizing the level of medical intervention in Ehpad, and deepening the training of Ehpad caregivers in geriatrics.

Interest of individual breast cancer screening by mammography in women aged over 75 years / Intérêt du dépistage individuel du cancer du sein par mammographie chez la femme âgée de plus de 75 ans

Organized breast cancer screening in France is recommended for women up to 74 years of age, while the frequency and severity of this cancer increases after 75 years. The aim of this work is to assess the potential benefits of extending organized screening. Methodology: Retrospective study of a continuous monocentric series of women over 75 having undergone surgery for breast cancer. The following variables were studied: addressing after screening or not, age at diagnosis, UICC stage and therapeutic measures (surgery by lumpectomy or mastectomy, lymph node dissection, adjuvant treatment with chemotherapy, radiotherapy or hormone therapy). Results: 185 women aged 82.8 ± 5.2 years [extreme ages 75 to 95] were included in the study. 136 (73.5%) breast cancers were discovered after palpation and 49 (26.5%) after screening mammography. The distribution by stage was: I - 38.8%, II - 39.5%, III - 15.1% and stage IV - 7%. 164 (87.7%), patients received surgical treatment: 115 lumpectomies (61.2%) and 49 mastectomies (26.5%). 51 (27.6%) patients underwent lymph node dissection. The distribution of adjuvant treatments was: chemotherapy 21.1%, radiotherapy 68.6%, or hormone therapy (79.5%), sometimes combined. Women not screened are older than women screened (84 ± 5.3 versus 79.5 ± 3.6 years; p < 0.0001). Cancers are diagnosed at a more advanced stage in non-screened patients compared to screened patients (p < 0.0001). While there is a higher proportion of stage I among screened patients (75.5%), stage II is the most frequent in women not screened (47%). Stage I and II are the majority in the latter (72%). In multivariate analysis with adjustment for age, screening made it possible to make a diagnosis at a less advanced stage (stage I-II vs II-IV: OR = 5.593; 95% CI [1.575­19.866]; p = 0.0078) and to have conservative surgery more often (lumpectomy vs mastectomy: OR = 2.645; 95% CI [1.079­6.493]; p = 0.0333) without more recourse to surgery (OR = 1.856 95% CI [0.207­16.612]; p = 0.58). After adjusting for age and stage, screening was no longer a determining factor in the choice of type of surgery (OR = 1.934; 95% CI [0.753­4.975]; p = 0.170). Conclusion: At the age when organized breast cancer screening in France stopped, there was a decrease in survival, a diagnosis at a higher stage and an increase in co-morbidities. Our study shows a change in management with heavier treatment, more complications and a greater loss of autonomy without screening. This pleads for a continuation beyond 75 years of the practice of mammography screening for breast cancer in elderly women.

Le dépistage du cancer du sein par mammographie est recommandé jusqu'à 74 ans alors que fréquence et gravité de ce cancer augmentent après 75 ans. Le but de ce travail est d'évaluer les bénéfices potentiels de l'extension du dépistage individuel par mammographie. Méthodologie: Étude rétrospective d'une série continue monocentrique de femmes de plus de 75 ans ayant consulté pour cancer du sein. Résultats: Cent-quatre-vingt-cinq femmes âgées (82,8 ± 5,2 ans [75-95]) ont été inclues. Cent-soixante-quatre (87,7 %) patientes ont bénéficié d'une chirurgie (115 tumorectomies (61,2 %), 49 mastectomies (26,5 %) et 51 curages ganglionnaires (27,6 %) avec traitement adjuvant (chimiothérapie 21,1 % ; radiothérapie 68,6 % ; ou hormonothérapie 79,5 %). Quarante-neuf cancers du sein ont été découverts après dépistage individuel par mammographie (26,5 %) chez des femmes moins âgées (79,5 ± 3,6 vs 84 ± 5,3 ans ; p < 0,0001), à un stade moins avancé (stade I-II vs III-IV : OR = 5,6 [1,5­19,8] ; p = 0,0078) avec une chirurgie plus conservatrice (tumorectomie vs mastectomie : OR = 2,6 [1,1­6,5] ; p = 0,0333). Conclusion: Le dépistage individuel du cancer du sein par mammographie permet une prise en charge moins lourde, à un stade moins avancé et devrait être poursuivi après 75 ans.

Cervical cancer in older women: Does age matter?

OBJECTIVES: Cervical cancer is frequently diagnosed in older women, but few studies have focused on cervical cancer in this specific population. The objectives of this study were to provide an overview of the demographic profile and therapeutic care of women with cervical cancer, and to identify whether age is a prognostic factor. STUDY DESIGN: Retrospective population-based study from a gynecological cancer registry in a French Regional University Hospital and Comprehensive Cancer Center. 292 women diagnosed with cervical cancer between January 1, 2005, and December 31, 2015, were included. They were classified into younger women (YW), that is, under 70 years of age (N = 228), and older women (OW), that is, aged 70 years or more (N = 64). MAIN OUTCOME MEASURES: The primary outcome was overall survival (OS). Cox proportional hazards models were developed to assess the impact of age on OS. RESULTS: Compared with YW, larger proportions of OW had comorbidities (14% vs 7% with a score ≥ 2 on the Charlson Comorbidity Index, P <0.001) and more advanced tumors (37.3% vs 19.7% with FIGO IV, P <0.001); the OW group had a lower treatment rate (81.3% vs 95.6%, P <0.001), and a smaller proportion had undergone surgery (37.5% vs 81.7%, P<.001) but a larger proportion had radiotherapy (67.2% vs 49.6%, P = .01). One-year, 5-year and 10-year OS rates were: 91.6%, 74.1% and 63.9% for YW, and 69.9%, 36.4% and 12.3% for OW, respectively (P <0.001). The hazard ratio for death was twice as high in OW compared with YW with cervical cancer (HR = 2.19 [1.41 - 3.40], P <0.001), independently of FIGO stage, histology, and comorbidities. CONCLUSIONS: The prognosis for cervical cancer depends on age. Screening with the G8 tool followed by a comprehensive geriatric assessment could lead to more suitable treatment being offered to older patients.

Prescription of Blood Lymphocyte Immunophenotyping in the Diagnosis of Lymphoid Neoplasms in Older Adults.

Lymphoid neoplasms are a heterogeneous group of lymphoid neoplastic diseases with multiple presentations, and varying prognoses. They are especially frequent in older patients (OPs) and the atypism of this frail elderly population can make the diagnostic process even more difficult. Blood lymphocyte immunophenotyping (BLI) is essential in rapid noninvasive diagnosis orientation and guides complementary investigations. To our knowledge, BLI prescription has never been evaluated in OPs. We hypothesized that, when there is a suspicion of lymphoid neoplasm in the geriatric population, a BLI is performed in view of various clinical or biological abnormalities. This study aimed to: (1) describe the characteristics of hospitalized OPs having undergone BLI for suspected lymphoid neoplasm, (2) identify the causes leading to BLI prescription, and (3) identify the most profitable criteria for BLI prescription. This was a descriptive retrospective study on 151 OPs aged ≥75 years who underwent BLI over a 2-year period. Regarding BLI prescriptions, eight had lymphocytosis, constituting the "lymphocytosis group" (LG+), while the 143 others had BLI prescribed for reasons other than lymphocytosis (LG-), mainly general weakness and anemia. In the LG-, we compared OPs with positive and negative BLI results. The criteria found to be profitable for BLI prescription were lymphadenopathy, splenomegaly, lymphocytosis, and thrombocytopenia. BLI identified circulating lymphoid neoplasms (positive BLI) in 21/151 OPs, mainly marginal zone lymphoma and chronic lymphocytic leukemia. In polymorbid OPs, as per our study population, the diagnostic and therapeutic complexity explained in part the sole use of indirect and minimally invasive diagnostic techniques such as BLI.

Criteria for taking an advance decision to limit the transfer to intensive care of patients aged 75 and over, hospitalised in an acute geriatric unit.

OBJECTIVE: Due to the diversity of the elderly population and medical practices, the decision to transfer elderly patients to an intensive care unit is complex. This study aimed to identify the criteria used to take an advance decision to limit transfer to an intensive care unit of patients hospitalised in an acute geriatric unit. METHODS: This retrospective study included, over a ten-month period, patients >75 years and hospitalised in an acute geriatric unit. They were divided into two groups according to whether or not an advanced decision to limit transfer to an intensive care unit had been taken. RESULTS: In total, 906 elderly patients were included in the study. Of them, 446 had no advance decision to limit transfer to an ICU. Univariate analysis showed a correlation between an advance decision to limit transfer to an ICU and a Mini Mental State Examination (MMSE) score of less than 20/30. Malnutrition had no impact on the advance decision. In multivariate analysis, the factors associated with an advance decision to limit transfer to an ICU were an age > 85 years, a hospitalisation in the last six months (Odds Ratio (OR) = 1.72, Confidence Interval (CI) 95% [1.23-2.39]), residence in a nursing home (OR = 1.93, 95% CI [1.18-0.16]) and the presence of bedsores (OR = 2.44, 95% CI [1.20-0.98]). A zero Charlson score was associated with the absence of an advance decision to limit transfer to an ICU (OR = 0.42, 95% CI [0.26-0.67]). CONCLUSION: Some criteria are common to geriatricians, intensive care doctors and emergency physicians, while others are discordant, illustrating differences in physicians' practices.

[Criteria of early limitation of transfer in intensive care unit of patients aged 75 and over hospitalized in an acute geriatric unit]. / Critères de limitation anticipée du transfert en réanimation des patients âgés de 75 ans et plus hospitalisés dans un service de gériatrie aiguë.

Because of heterogeneity of the elderly population and medical practices, the decision of admission of elderly patients (EP) in intensive care unit is more complex. This study aimed to determine the decision criteria for an early limitation of transfer in intensive care unit (ELTICU) of patients hospitalized in an acute geriatric unit. This retrospective study included, over a 10-month period, patients ≥75 years and hospitalized in an acute geriatric unit. They were divided into 2 groups according to whether or not an ELTICU decision was taken. In total, 906 EP were included among them 446 with no ELTICU decision. Univariate analysis showed a correlation between ELTICU and a Mini Mental Status score of less than 20/30. Malnutrition had no impact on ELTICU decision. In multivariate analysis, the factors associated with an ELTICU decision were an age ≥ 85 years, an hospitalization in the last 6 months (Odds Ratio (OR) = 1.72, Confidence Interval (CI) 95% [1.23-2.39]), life in a nursing home (OR = 1.93, 95% CI [1.18-3.16]) and the presence of bedsore(s) (OR = 2.44, 95% CI [1.20-4.98]). A null Charlson score was associated with the absence of an ELTICU decision (OR = 0.42, 95% CI [0.26-0.67]). Some criteria are shared between geriatricians, resuscitators and emergency physicians, while others are discordant, illustrating differences in physicians' practices.

Analysis of COVID-19 in Professionals Working in Geriatric Environment: Multicenter Prospective Study.

Healthcare workers (HCWs) are exposed to a higher risk of coronavirus disease (COVID-19) contamination. This prospective multicenter study describes the characteristics of HCWs tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) while working in a geriatric environment. We also compared HCWs with a positive reverse transcription polymerase chain reaction (RTPCR) assay (RTPCR+ group) and those with a negative test result (RTPCR- group). Between 15/5/2020 and 15/9/2020, 258 HCWs, employed in the acute geriatric unit (AGU), geriatric rehabilitation unit (GRU) or nursing home of three hospitals in Burgundy (France) were invited to complete an online survey. Among the 171 respondents, 83 participants, with mean age 42 years and 87.9% female, were tested for SARS-CoV-2 infection. Among these 83 participants, COVID-19 was confirmed in 38 cases (RTPCR+ group) of which 36 were symptomatic, and the RTPCR assay was negative in 45 cases (RTPCR- group) of which 20 participants were symptomatic. A total of 22.9% (of 83) had comorbidities, 21.7% were active smokers, and 65.1% had received the flu vaccine. A total of 37.3% worked in AGU, 19.3% in GRU and 16.9% in nursing homes. The most common symptom described was headache (23.2%), followed by fatigue or cough (12.5% each), and fever or myalgia (10.7% each). There were more participants with normal body mass index (p = 0.03) in the RTPCR+ group. In contrast, there were more users of non-steroidal anti-inflammatory drugs (p = 0.01), active smokers (p = 0.03) and flu vaccinated (p = 0.01) in the RTPCR- group. No difference was found between the two groups for the type of work (p = 0.20 for physicians and p = 0.18 for nurses). However, acquiring COVID-19 was significantly associated with working in AGU (p < 0.001) and nursing homes (p = 0.001). There were significantly more users of surgical masks (p = 0.035) in the RTPCR+ group and more filtering facepiece-2 mask users (p = 0.016) in the RTPCR- group. Our results reflect the first six months of the COVID-19 pandemic in France. Further studies are needed to evaluate and track the risks and consequences of COVID-19 in HCWs.

Level of Medical Intervention in Geriatric Settings: Decision Factors and Correlation With Mortality.

OBJECTIVES: Level of medical intervention (LMI) has to be adapted to each patient in geriatric care. LMI scales intend to help nonintensive care (NIC) decisions, giving priority to patient choice and collegial discussion. In the present study, we aimed to assess the parameters associated with the NIC decision and whether these parameters differ from those associated with in-hospital mortality. DESIGN: Prospective observational study. SETTING AND PARTICIPANTS: All consecutive patients from a French 62-bed acute geriatric unit over 1 year. METHODS: Factors from the geriatric assessment associated with the decision of NIC were compared with those associated with in-hospital and 1-year mortality, in univariate and multivariate analyses. RESULTS: In total, 1654 consecutive patients (median age 87 years) were included. Collegial reflection led to NIC decision for 532 patients (32%). In-hospital and 1-year mortality were 22% and 54% in the NIC group vs 2% and 27% in the rest of the cohort (P < .001 for both). In multivariable analysis, high Charlson Comorbidity Index [odds ratio (OR) 1.15, 95% confidence interval (CI) 1.06-1.23, per point], severe neurocognitive disorders (OR 2.78, 95% CI 1.67-4.55), dependence (OR 1.92, 95% CI 1.45-2.59), and nursing home residence (OR 2.38, 95% CI 1.85-3.13) were highly associated with NIC decision but not with in-hospital mortality. Conversely, acute diseases had little impact on LMI despite their high short-term prognostic burden. CONCLUSIONS AND IMPLICATIONS: Neurocognitive disorders and dependence were strongly associated with NIC decision, even though they were not significantly associated with in-hospital mortality. The decision-making process of LMI therefore seems to go beyond the notion of short-term survival.

Atypical Presentation of Bacteremic Urinary Tract Infection in Older Patients: Frequency and Prognostic Impact.

In older patients, urinary tract infection (UTI) often has an atypical clinical presentation, making its diagnosis difficult. We aimed to describe the clinical presentation in older inpatients with UTI-related bacteremia and to determine the prognostic impact of atypical presentation. This cohort study included all consecutive patients older than 75 years hospitalized in a university hospital in 2019 with a UTI-related gram-negative bacillus (GNB) bacteremia, defined by blood and urine cultures positive for the same GNB, and followed up for 90 days. Patients with typical symptoms of UTI were compared to patients with atypical forms. Among 3865 inpatients over 75 with GNB-positive urine culture over the inclusion period, 105 patients (2.7%) with bacteremic UTI were included (mean age 85.3 ± 5.9, 61.9% female). Among them, UTI symptoms were reported in only 38 patients (36.2%) and 44 patients (41.9%) had no fever on initial management. Initial diagnosis of UTI was made in only 58% of patient. Mortality at 90 days was 23.6%. After adjustment for confounders, hyperthermia (HR = 0.37; IC95 (0.14-0.97)) and early UTI diagnosis (HR = 0.35; IC95 (0.13-0.94)) were associated with lower mortality, while UTI symptoms were not associated with prognosis. In conclusion, only one third of older patients with UTI developing bacteremia had UTI symptoms. However, early UTI diagnosis was associated with better survival.

Direct Oral Anticoagulants versus Vitamin K Antagonists in Patients Aged 80 Years and Older.

The effectiveness of direct oral anticoagulants (DOAC) is non-inferior to vitamin K antagonists (VKA) to treat atrial fibrillation and venous thromboembolism (VTE). In this cross-sectional study, we compared older persons taking DOACs to those taking VKAs. We included ambulatory individuals ≥80 years, affiliated to Mutualité Sociale Agricole of Burgundy, who were refunded for a medical prescription in September 2017. The demographic conditions, registered chronic diseases (RCD), and number and types of prescribed drugs were compared in the DOAC group and VKA group. Of the 3190 included individuals, 1279 (40%) were prescribed DOACs and 1911 (60%) VKAs. Individuals taking VKAs were older than those taking DOACs (87.11 vs. 86.35 years). In the DOAC group, there were more women (51.92% vs. 48.25%) (p = 0.043), less RCD (89.60% vs. 92.73%) (p = 0.002), less VTE (1.80% vs. 6.59%), less severe heart failure (58.09% vs. 67.87%), less severe hypertension (18.22% vs. 23.60%), less severe kidney diseases (1.49% vs. 3.82%), and fewer drugs per prescription (6.15 vs. 6.66) (p < 0.01 for all). The DOAC group were also less likely to be taking angiotensin receptor blockers (10.79% vs. 13.97%), furosemide (40.81% vs. 49.66%) or digoxin (10.32% vs. 13.66%) than the VKA group (p = 0.009, p < 0.001, and p = 0.005). DOACs were less prescribed than VKAs. Individuals taking VKAs were older and had more severe comorbidities and more drugs per prescription than those taking DOACs.

Not COVID-19, Don't Overlook Pneumocystis in Patients on Gefitinib!

An 82-year-old woman treated for advanced lung cancer with gefitinb was admitted to the emergency unit complaining of dyspnea. Chest computed tomography found abnormalities classified as possible diffuse COVID-19 pneumonia. RT-PCR for Sars-Cov-2 was twice negative. PCR for Pneumocystis jirovecii was positive on bronchoalveolar lavage. The final diagnosis was Pneumocystis jirovecii pneumonia. Therefore, physicians must be careful not to misdiagnose COVID-19, especially in cancer patients on small-molecule therapeutics like gefitinib and corticosteroids.

The Pivotal Role of Viruses in the Pathogeny of Chronic Lymphocytic Leukemia: Monoclonal (Type 1) IgG K Cryoglobulinemia and Chronic Lymphocytic Leukemia Diagnosis in the Course of a Human Metapneumovirus Infection.

BACKGROUND: Type-1 cryoglobulinemia (CG) is a rare disease associated with B-cell lymphoproliferative disorder. Some viral infections, such as Epstein-Barr Virus infections, are known to cause malignant lymphoproliferation, like certain B-cell lymphomas. However, their role in the pathogenesis of chronic lymphocytic leukemia (CLL) is still debatable. Here, we report a unique case of Type-1 CG associated to a CLL transformation diagnosed in the course of a human metapneumovirus (hMPV) infection. CASE PRESENTATION: A 91-year-old man was initially hospitalized for delirium. In a context of febrile rhinorrhea, the diagnosis of hMPV infection was made by molecular assay (RT-PCR) on nasopharyngeal swab. Owing to hyperlymphocytosis that developed during the course of the infection and unexplained peripheral neuropathy, a type-1 IgG Kappa CG secondary to a CLL was diagnosed. The patient was not treated for the CLL because of Binet A stage classification and his poor physical condition. CONCLUSIONS: We report the unique observation in the literature of CLL transformation and hMPV infection. We provide a mini review on the pivotal role of viruses in CLL pathophysiology.