Molecularly matched targeted therapy: a promising approach for refractory metastatic melanoma.

BACKGROUND: Only a fraction of patients with metastatic melanoma derive durable benefit from approved treatments. The clinical impact of personalized medicine strategies for melanoma, apart from BRAF, NRAS, or CKIT targeting, has rarely been reported. MATERIALS AND METHODS: By means of the Group of Cutaneous Oncology of the French Society of Dermatology, we retrospectively included all patients with advanced melanoma aged 18 years and older for whom molecular testing identified one or more actionable molecular alterations and who accordingly received molecularly matched therapy. We excluded patients with only BRAF, NRAS, or CKIT alterations and patients who received molecularly matched therapy for less than 15 days. RESULTS: We included 26 patients with a median follow-up of 8 months (1-54), a median age of 63 years (24-89), and a sex ratio of 2.7. These patients had been heavily pretreated, and 64% had elevated LDH levels. The disease control rate was 38%, with 4 cases of partial response (overall response rate: 15%) and 6 of stable disease for at least 6 months. The median duration of treatment was 3.1 months (0.9-13.5). Among patients with disease control, the median duration of control was 6.6 months (2.6-13.5) and 3 cases were ongoing at the end of the study. Patients with controlled disease had GNA11, MAP2K1, FYCO1-RAF1, HRAS, ATM, CCND1, MDM2/CDK4, and CDKN2A/NRAS alterations. CONCLUSIONS: High-throughput sequencing followed by matched targeted therapy is a promising approach for patients with advanced melanoma refractory to approved treatments.

Cytidine deaminase status as a marker of response to azacytidine treatment in MDS and AML patients.

Azacitidine (Aza) is a mainstay of treatment for patients with acute myeloid leukaemia (AML) ineligible for induction chemotherapy and other high-risk myelodysplastic syndromes (MDS). Only half of patients respond, and almost all will eventually relapse. There are no predictive markers of response to Aza. Aza is detoxified in the liver by cytidine deaminase (CDA). Here, we investigated the association between CDA phenotype, toxicity and efficacy of Aza in real-world adult patients. Median overall survival (OS) was 15 months and 13 months in AML and high-risk MDS patients respectively. In addition, our data suggest that delaying Aza treatment was not associated with lack of efficacy and should not be considered a signal to switch to an alternative treatment. Half of the patients had deficient CDA activity (i.e. <2 UA/mg), with a lower proportion of deficient patients in MDS patients (34%) compared to AML patients (67%). In MDS patients, CDA deficiency correlated with longer landmark OS (14 vs. 8 months; p = 0.03), but not in AML patients. Taken together, our data suggest that CDA is an independent covariate and may therefore be a marker for predicting clinical outcome in MDS patients treated with Aza.

Anticancer drug delivery by focused ultrasound-mediated blood-brain/tumor barrier disruption for glioma therapy: From benchside to bedside.

The therapeutic management of gliomas remains particularly challenging. Brain tumors present multiple obstacles that make therapeutic innovation complex, mainly due to the presence of blood-tumor and blood-brain barriers (BTB and BBB, respectively) which prevent penetration of anticancer agents into the brain parenchyma. Focused ultrasound-mediated BBB disruption (FUS-BBBD) provides a physical method for non-invasive, local, and reversible BBB disruption. The safety of this technique has been demonstrated in small and large animal models. This approach promises to enhance drug delivery into the brain tumor and therefore to improve survival outcomes by repurposing existing drugs. Several clinical trials continue to be initiated in the last decade. In this review, we provide an overview of the rationale behind the use of FUS-BBBD in gliomas and summarize the preclinical studies investigating different approaches (free drugs, drug-loaded microbubbles and drug-loaded nanocarriers) in combination with this technology in in vivo glioma models. Furthermore, we discuss the current state of clinical trials and devices developed and review the challenges to overcome for clinical use of FUS-BBBD in glioma therapy.

Tocilizumab versus anakinra in COVID-19: results from propensity score matching.

Background: Tocilizumab and anakinra are anti-interleukin drugs to treat severe coronavirus disease 2019 (COVID-19) refractory to corticosteroids. However, no studies compared the efficacy of tocilizumab versus anakinra to guide the choice of the therapy in clinical practice. We aimed to compare the outcomes of COVID-19 patients treated with tocilizumab or anakinra. Methods: Our retrospective study was conducted in three French university hospitals between February 2021 and February 2022 and included all the consecutive hospitalized patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection assessed by RT-PCR who were treated with tocilizumab or anakinra. A propensity score matching was performed to minimize confounding effects due to the non-random allocation. Results: Among 235 patients (mean age, 72 years; 60.9% of male patients), the 28-day mortality (29.4% vs. 31.2%, p = 0.76), the in-hospital mortality (31.7% vs. 33.0%, p = 0.83), the high-flow oxygen requirement (17.5% vs. 18.3%, p = 0.86), the intensive care unit admission rate (30.8% vs. 22.2%, p = 0.30), and the mechanical ventilation rate (15.4% vs. 11.1%, p = 0.50) were similar in patients receiving tocilizumab and those receiving anakinra. After propensity score matching, the 28-day mortality (29.1% vs. 30.4%, p = 1) and the rate of high-flow oxygen requirement (10.1% vs. 21.5%, p = 0.081) did not differ between patients receiving tocilizumab or anakinra. Secondary infection rates were similar between the tocilizumab and anakinra groups (6.3% vs. 9.2%, p = 0.44). Conclusion: Our study showed comparable efficacy and safety profiles of tocilizumab and anakinra to treat severe COVID-19.

Molecular Imaging of Ultrasound-Mediated Blood-Brain Barrier Disruption in a Mouse Orthotopic Glioblastoma Model.

Glioblastoma (GBM) is an aggressive and malignant primary brain tumor. The blood-brain barrier (BBB) limits the therapeutic options available to tackle this incurable tumor. Transient disruption of the BBB by focused ultrasound (FUS) is a promising and safe approach to increase the brain and tumor concentration of drugs administered systemically. Non-invasive, sensitive, and reliable imaging approaches are required to better understand the impact of FUS on the BBB and brain microenvironment. In this study, nuclear imaging (SPECT/CT and PET/CT) was used to quantify neuroinflammation 48 h post-FUS and estimate the influence of FUS on BBB opening and tumor growth in vivo. BBB disruptions were performed on healthy and GBM-bearing mice (U-87 MG xenograft orthotopic model). The BBB recovery kinetics were followed and quantified by [99mTc]Tc-DTPA SPECT/CT imaging at 0.5 h, 3 h and 24 h post-FUS. The absence of neuroinflammation was confirmed by [18F]FDG PET/CT imaging 48 h post-FUS. The presence of the tumor and its growth were evaluated by [68Ga]Ga-RGD2 PET/CT imaging and post-mortem histological analysis, showing that tumor growth was not influenced by FUS. In conclusion, molecular imaging can be used to evaluate the time frame for systemic treatment combined with transient BBB opening and to test its efficacy over time.

Synthesis, In Vitro Antiproliferative Activity, and In Silico Evaluation of Novel Oxiranyl-Quinoxaline Derivatives.

The quinoxaline core is a promising scaffold in medicinal chemistry. Multiple quinoxaline derivatives, such as the topoisomerase IIß inhibitor XK-469 and the tissue transglutaminase 2 inhibitor GK-13, have been evaluated for their antiproliferative activity. Previous work reported that quinoxaline derivatives bearing an oxirane ring present antiproliferative properties against neuroblastoma cell lines SK-N-SH and IMR-32. Likewise, quinoxalines with an arylethynyl group displayed promising antineoplastic properties against glioblastoma and lung cancer cell lines, U87-MG and A549 respectively. Here, 40 new quinoxaline derivatives bearing an oxirane ring were synthesized using a tetrakis(dimethylamino)ethylene (TDAE) strategy and a Sonogashira cross-coupling reaction. Each reaction with TDAE furnished a pair of diastereoisomers cis and trans. These new compounds formed two series according to the substitution of position 2 on the quinoxaline core, with chlorine or phenylacetylene respectively. Each of these isomers was evaluated for antiproliferative activity against neuroblastoma cell lines SK-N-SH and IMR-32 by MTT assay. All cell viability assay results were analyzed using R programming, as well as a statistical comparison between groups of compounds. Our evaluation showed no difference in drug sensitivity between the two neuroblastoma cell lines. Moreover, trans derivatives were observed to display better activities than cis derivatives, leading us to conclude that stereochemistry plays an important role in the antiproliferative activity of these compounds. Further support for this hypothesis is provided by the lack of improvement in antineoplastic activity following the addition of the phenylacetylene moiety, probably due to steric hindrance. As a result, compounds with nitrofuran substituents from the TDAE series demonstrated the highest antiproliferative activity with IC50 = 2.49 ± 1.33 µM and IC50 = 3.96 ± 2.03 µM for compound 11a and IC50 = 5.3 ± 2.12 µM and IC50 = 7.12 ± 1.59 µM for compound 11b against SK-N-SH and IMR-32, respectively. Furthermore, an in silico study was carried out to evaluate the mechanism of action of our lead compounds and predict their pharmacokinetic properties.

Perfluorocarbon Nanodroplets as Potential Nanocarriers for Brain Delivery Assisted by Focused Ultrasound-Mediated Blood-Brain Barrier Disruption.

The management of brain diseases remains a challenge, particularly because of the difficulty for drugs to cross the blood-brain barrier. Among strategies developed to improve drug delivery, nano-sized emulsions (i.e., nanoemulsions), employed as nanocarriers, have been described. Moreover, focused ultrasound-mediated blood-brain barrier disruption using microbubbles is an attractive method to overcome this barrier, showing promising results in clinical trials. Therefore, nanoemulsions combined with this technology represent a real opportunity to bypass the constraints imposed by the blood-brain barrier and improve the treatment of brain diseases. In this work, a stable freeze-dried emulsion of perfluorooctyl bromide nanodroplets stabilized with home-made fluorinated surfactants able to carry hydrophobic agents is developed. This formulation is biocompatible and droplets composing the emulsion are internalized in multiple cell lines. After intravenous administration in mice, droplets are eliminated from the bloodstream in 24 h (blood half-life (t1/2) = 3.11 h) and no long-term toxicity is expected since they are completely excreted from mice' bodies after 72 h. In addition, intracerebral accumulation of tagged droplets is safely and significantly increased after focused ultrasound-mediated blood-brain barrier disruption. Thus, the proposed nanoemulsion appears as a promising nanocarrier for a successful focused ultrasound-mediated brain delivery of hydrophobic agents.

Acceptance, efficacy, and safety of COVID-19 vaccination in older patients with cancer.

PURPOSE: The COVID-19 vaccination campaign began in December 2020, in France, and primarily targeted the oldest people. Our study aimed to determine the level of acceptance of vaccination in a population of older patients with cancer. METHODS: From January 2021, we offered vaccination with the BNT162b2 COVID-19 vaccine to all patients 70 years and older referred to our geriatric oncology center in Marseille University Hospital (AP-HM) for geriatric assessment before initiation of an oncological treatment. Objectives were to evaluate acceptance rate of COVID-19 vaccination and to assess vaccine safety, reactogenicity, and efficacy two months after the first dose. RESULTS: Between January 18, 2021 and May 7, 2021, 150 older patients with cancer were offered vaccination after a geriatric assessment. The majority were men (61.3%), with a mean age of 81 years. The two most frequent primary tumors were digestive (29.4%) and thoracic (18%). The vaccine acceptance rate was 82.6% and the complete vaccination rate (2 doses) reached 75.3%. Among the vaccinated patients, 15.9% reported mild side effects after the first dose and 23.4% after the second dose, mostly arm pain and fatigue. COVID-19 cases were observed in 5.1% of vaccinated patients compared with 16.7% in unvaccinated patients. Of the 22 vaccinated patients who agreed to have their serum tested, 15 had antibodies against the spike protein at day 21 after the first dose. CONCLUSION: Our study showed a high acceptance rate of COVID-19 vaccination, with good tolerance in this frail population. These results highlight the benefits of organizing vaccination campaigns at the very beginning of oncological management in older patients. CLINICAL TRIAL REGISTRATION: This study was registered May 23, 2019 in ClinicalTrials.gov (NCT03960593).

Telemedication Reviews to Optimize Medication Prescription for Older People in Nursing Homes.

Introduction: Older people living in nursing homes (NH) are at a higher risk of preventable drug-related adverse events because of age-related physiological changes, polypathology, and polypharmacy. NH residents are particularly exposed to potentially inappropriate medications (PIMs). Many strategies have been developed to improve the quality and the safety of drug prescription in NH, including medication reviews (MRs). Methods: In the context of the application of telemedicine, we developed and are currently implementing a novel hospital expert-based MRs through tele-expertise (or "telemedication review," telemedication reviews hereafter [TMR]) in French NH residents. The impact of these TMR on unplanned hospitalizations 3 months after implementation is assessed. TMR consider all available sociodemographic, clinical, biological, and pharmaceutical data pertaining to the patient and are performed in accordance with their health care objectives. Results: The preliminary results for the 39 TMRs performed to date (September 2021) showed that a total of 402 PIMs were detected, and all residents had at least one PIM. We also present the feasibility and the usefulness of this novel TMR for NH, illustrating these preliminary results with two concrete TMR experiences. Among the 39 TMR performed, the average acceptance rate of expert recommendations made to general practitioners (GP) working in NH was ∼33%. Discussion and Conclusions: The success of this novel TMR depends on how the proposed prescription adjustments made by the hospital expert team are subsequently integrated into health care practices. The low acceptance rate by GP highlights the need to actively involve these professionals in the process of developing TMR, with a view to encouraging them to act on proposed adjustments.

Factors Associated With COVID-19 Hospitalizations and Deaths in French Nursing Homes.

OBJECTIVES: To describe the clinical characteristics and management of residents in French nursing homes with suspected or confirmed coronavirus disease 2019 (COVID-19) and to determine the risk factors for COVID-19-related hospitalization and death in this population. DESIGN: A retrospective multicenter cohort study. SETTING AND PARTICIPANTS: Four hundred eighty nursing home residents with suspected or confirmed COVID-19 between March 1 and May 20, 2020, were enrolled and followed until June 2, 2020, in 15 nursing homes in Marseille's greater metropolitan area. METHODS: Demographic, clinical, laboratory, treatment type, and clinical outcome data were collected from patients' medical records. Multivariable analysis was used to determine factors associated with COVID-19-related hospitalization and death. For the former, the competing risk analysis-based on Fine and Gray's model-took death into account. RESULTS: A total of 480 residents were included. Median age was 88 years (IQR 80-93), and 330 residents were women. A total of 371 residents were symptomatic (77.3%), the most common symptoms being asthenia (47.9%), fever or hypothermia (48.1%), and dyspnea (35.6%). One hundred twenty-three patients (25.6%) were hospitalized and 96 (20%) died. Male gender [specific hazard ratio (sHR) 1.63, 95% confidence interval (CI) 1.12-2.35], diabetes (sHR 1.69, 95% CI 1.15-2.50), an altered level of consciousness (sHR 2.36, 95% CI 1.40-3.98), and dyspnea (sHR 1.69, 95% CI 1.09-2.62) were all associated with a greater risk of COVID-19-related hospitalization. Male gender [odds ratio (OR) 6.63, 95% CI 1.04-42.39], thermal dysregulation (OR 2.64, 95% CI 1.60-4.38), falls (2.21 95% CI 1.02-4.75), and being aged >85 years (OR 2.36, 95% CI 1.32-4.24) were all associated with increased COVID-19-related mortality risk, whereas polymedication (OR 0.46, 95% CI 0.27-0.77) and preventive anticoagulation (OR 0.46, 95% CI 0.27-0.79) were protective prognostic factors. CONCLUSIONS AND IMPLICATIONS: Male gender, being aged >85 years old, diabetes, dyspnea, thermal dysregulation, an altered level of consciousness, and falls must all be considered when identifying and protecting nursing home residents who are at greatest risk of COVID-19-related hospitalization and death.

Development of a multi-functional preclinical device for the treatment of glioblastoma.

Glioblastoma multiforme (GBM) is one of the most common and aggressive malignant primary brain tumors in adults. The treatment of GBM is limited by the blood-brain barrier (BBB), which limits the diffusion of appropriate concentrations of therapeutic agents at the tumor site. Among experimental therapies, photo-thermal therapy (PTT) mediated by nanoparticles is a promising strategy. To propose a preclinical versatile research instrument for the development of new PTT for GBM, a multipurpose integrated preclinical device was developed. The setup is able to perform: i) BBB permeabilization by focused ultrasound sonication (FUS); ii) PTT with continuous wave laser; iii) in situ temperature monitoring with photo-acoustic (PA) measurements. In vivo preliminary subcutaneous and transcranial experiments were conducted on healthy or tumor-bearing mice. Transcranial FUS-induced BBB permeabilization was validated using single photon emission computed tomography (SPECT) imaging. PTT capacities were monitored by PA thermometry, and are illustrated through subcutaneous and transcranial in vivo experiments. The results show the therapeutic possibilities and ergonomy of such integrated device as a tool for the validation of future treatments.

Centenarians in nursing homes during the COVID-19 pandemic.

BACKGROUND: Centenarians are known to be successful agers compared to other older adults. OBJECTIVE: The objective of the present study was to compare coronavirus disease (COVID-19) symptoms and outcomes in centenarians and other residents living in nursing homes. Design-Setting-Subjects-Methods: A retrospective multicenter cohort study was conducted using data from 15 nursing homes in the Marseille area. Older residents with confirmed COVID-19 between March and June 2020 were enrolled. The clinical and biological characteristics, the treatment measures, and the outcomes in residents living in these nursing homes were collected from the medical records. RESULTS: A total of 321 residents were diagnosed with COVID-19 including 12 centenarians. The median age was 101 years in centenarians and 89 years in other residents. The most common symptoms were asthenia and fever. Three centenarians (25%) experienced a worsening of pre-existing depression (vs. 5.5% of younger residents; p = 0.032). Mortality was significantly higher in centenarians than in younger residents (50% vs. 21.3%, respectively; p = 0.031). A quarter of the younger residents and only one centenarian were hospitalized. However, 33.3% of the centenarians received treatment within the context of home hospitalization. CONCLUSION: Worsening of pre-existing depression seems to be more frequent in centenarians with COVID-19 in nursing homes. This population had a higher mortality rate but a lower hospitalization rate than younger residents.

Medication reconciliation in the geriatric unit: impact on the maintenance of post-hospitalization prescriptions.

Background Medication reconciliation prevents medication errors at care transition points. This process improves communication with general practitioners regarding the reasons for therapeutic changes, allowing those changes to be maintained after hospital discharge. Objective To investigate the impact of medication reconciliation in geriatrics on the sustainability of therapeutic optimization after hospital discharge. Setting This study was conducted in a geriatric unit in a University Hospital Centre in France. Method This was a retrospective study. For 6 months, all patients over 65 years who underwent the process of medication reconciliation performed by a clinical hospital pharmacist and a physician at admission and discharge, were included. A comparison between drug prescriptions at hospital discharge and the first prescription made outside the hospital was made to identify any differences. Main outcome measure The main outcome measures were the provision of the results of the medication reconciliation performed in the hospital to the relevant general practitioner, the subsequent acceptance of that information, the type of medication discrepancies one month after discharge and the therapeutic classes affected by the modifications. Results Among the 112 patients, medication reconciliation allowed us to identify and correct 87 unintentional discrepancies at admission (88% corrected) and 54 at discharge (92% corrected). Patients were discharged to homes or nursing homes (61%), geriatric rehabilitation units (38%) or psychiatric clinics (1%). A general practitioner wrote the first prescription renewal a mean of 36 ± 23 days after discharge, having been made aware of the medication reconciliation in only 24% of the cases (received and taken into account). The impact was a decrease in the number of patients with at least one discrepancy. Twenty-five percent of general practitioners who were aware about the medication reconciliation process accepted all therapeutic changes, while only 7% of those who were not informed did so (p = 0.02). The number of medication discrepancies observed was correlated with the number of medications for which prescriptions were renewed (p < 0.01). Conclusion Medication reconciliation involving therapeutic optimization and the justification of changes is essential to ensure the safety of the prescriptions written for patients. However, its impact after discharge is hampered by the fact that the results are often not received or taken into account by general practitioners. Taking medication reconciliation into account was associated with a significant increase in prescriptions that maintained therapeutic changes made in the hospital, confirming the positive impact of communication between care providers on therapeutic optimization.

Acceptability of a Novel Telemedication Review for Older Adults in Nursing Homes in France: A Qualitative Study.

PURPOSE: In France, polypharmacy among older people living in nursing homes (NH) is a major public health concern. In this context, the randomized controlled trial TEM-EHPAD was recently launched in various NH in southern France to evaluate the impact of implementing a novel telemedication review (TMR) on hospital admission rates of NH residents at high risk of iatrogenic disease. A qualitative study was integrated into the main trial study to assess general practitioners' (GP) and other NH healthcare professionals' (HP) acceptability of the proposed TMR before its implementation. MATERIAL AND METHODS: A qualitative study using face-to-face semi-structured interviews was conducted with 16 HP before the beginning of the intervention. A manual thematic analysis was performed on the transcribed interviews. RESULTS: Four main themes emerged from the thematic analysis: HP perceptions of the TMR, difficulties related to medication management for NH residents, HP perceptions of the roles of different professionals, and facilitators of good practices. Most participants were favorable to the TMR, but some GP expressed fears about loss of control over their prescription writing. CONCLUSION: This study fulfilled its objective to assess pre-intervention acceptability by GP and other HP. Results provided important information about how to adapt the TMR intervention to make it more acceptable to HP who will be involved in TEM-EHPAD. One of the main recommendations is the importance of providing participating GP with the opportunity to take part in the process of reviewing prescriptions.

Octogenarians treated for thoracic and lung cancers: Impact of comprehensive geriatric assessment.

BACKGROUND: Lung cancer affects older and older old adults and is the leading cause of death by cancer. Comprehensive Geriatric Assessment (CGA) is recommended before and during cancer treatment to guide therapy management in this population. METHODS: This study was conducted between September 2015 and January 2019 at Marseille University Hospital (AP-HM). During this period, all consecutive outpatients 70 years or older referred for a CGA before initiation of lung cancer treatment were enrolled. The objective of this study was to compare lung and thoracic cancer management of octogenarians (≥80 years) and their geriatric profile versus patients aged 70 to 79 years (<80 years). FINDINGS: In our study, 228 patients were recruited. The median age was 78.7 ± 5 years. There were 94 octogenarians (41.2%), 36.2% of them were diagnosed with stage IV neoplasm and the most common treatment was chemotherapy (43.6%). The logistic regression analysis highlights that handgrip strength was the most commonly impaired domain (OR 2.3; 95% CI [1.3-4.3]) in octogenarians and that they are more likely than their younger counterparts to be treated by targeted therapy (OR 9.8; 95% CI [1.0-92.9]). Overall survival (OS) was similar in both age groups (log rank = 0,95). INTERPRETATION: In our study, octogenarians and patients <80 years had equivalent survival, across the different thoracic cancer treatments and tumor stages. Measure of muscle strength in CGA could be very useful in a clinical setting to help improve the management of older old patients treated for lung or thoracic cancer.

Prognostic Value of the B12/CRP Index in Older Systemically Treatable Cancer Patients.

BACKGROUND: While comprehensive geriatric assessment (CGA) in older patients treated for cancer assesses several related domains, it does not include standardized biological tests. The present study aimed to: (1) assess the prognosis value of the B12/CRP index (BCI) in a population of systemically treatable older patients with cancer and (2) analyze the association between BCI value and pre-existing geriatric frailty. METHOD: We conducted a retrospective observational study between January 2016 and June 2020 at Marseille University Hospital. All consecutive cancer patients aged 70 years and over before initiating systemic therapy were included. RESULTS: Of the 863 patients included, 60.5% were men and 42.5% had metastatic stage cancer. Mean age was 81 years. The low-BCI group (≤10,000) had a significantly longer survival time than the mid-BCI (10,000 < BCI ≤ 40,000) and high-BCI (BCI > 40,000) groups (HR = 0.327, CI95% [0.26-0.42], p-value = 0.0001). Mid- and high-BCI (BCI > 40,000) values were associated with impaired functional status and malnutrition. CONCLUSION: A BCI > 10,000 would appear to be a good biological prognostic factor for poor survival times and pre-existing geriatric impairment in older cancer patients before they initiate systemic treatment.

Older Patients Treated for Lung and Thoracic Cancers: Unplanned Hospitalizations and Overall Survival.

BACKGROUND: Lung cancer affects older adults and is the leading solid tumor in terms of death. A Comprehensive Geriatric Assessment (CGA) is recommended before cancer treatment to guide therapy management. PATIENTS AND METHODS: This study was conducted between September 2015 and January 2019. During this period of time, all consecutive older outpatients referred for a CGA before initiation of lung or thoracic tumor treatment were included. The objectives were to describe the impact of geriatric factors on unplanned hospitalizations and overall survival (OS). The study was approved by a local ethics committee. RESULTS: Overall, 228 patients were recruited. The median age was 78.7 ± 5 years. The majority (82%) of patients were diagnosed with non-small-cell lung cancer, and the most common (40.4%) treatment was systemic therapy. In multivariate analysis, factors associated with unplanned hospitalizations within the first 3 months were male gender (adjusted odds ratio [aOR], 3.3; 95% confidence interval [CI], 1.5-7.2), systemic therapy (aOR, 2.6; 95% CI, 1.1-6.2), and fall history (aOR, 3.6; 95% CI, 1.6-8.2). Factors associated with a decrease in OS in the multivariate Cox model analysis were male gender (hazard ratio [HR], 3.9; 95% CI, 2.1-7.3), stage IV (HR, 1.6; 95% CI, 1.0-2.6), G8 ≤ 14 (HR, 3.5; 95% CI, 1.1-11.4), systemic therapy (HR, 2.6; 95% CI, 1.2-5.5), Eastern Cooperative Oncology Group performance status ≥ 2 (HR, 2.0; 95% CI, 1.2-3.4), and impaired handgrip strength (HR, 1.6; 95% CI, 1.0-2.5). CONCLUSION: G8 score and handgrip strength are important to predict OS in older adults treated for thoracic tumors. In the CGA, fall history was associated with unplanned hospitalization.

Medication Reconciliation Associated with Comprehensive Geriatric Assessment in Older Patients with Cancer: ChimioAge Study.

BACKGROUND: Polymorbidity induces polypharmacy in older patients may lead to potential drug-drug interactions (DDI) which can modify the tolerance and safety of oncological treatments and alter the intended therapeutic effect. The objective of our study was to describe the decision-making process for oncological treatment and related outcomes, in a population of older adults undergoing a comprehensive geriatric assessment (CGA) associated to a comprehensive medication reconciliation (CMR) prior to initiating oncological treatment. METHODS: ChimioAge is a prospective observational study conducted between 01/2017 and 07/2018 at Marseille University Hospital and approved by the French National Ethics Committee. It comprised all consecutive patients aged 70 years and over who were referred for a CGA as part of CMR, before initiating systemic treatment. RESULTS: One hundred and seventy-one cancer patients were included. Mean age was 79.2 years, over half had metastatic cancers, 75% had an ECOG performance status zero or one, and two-thirds were independent in daily activities. Two-thirds of the patients had polypharmacy and the CMR identified potential DDI with systemic treatment in 43.3% of patients. Following the CGA, the CMR and the hospital oncologists decision, 30% of the patients received adapted systemic treatment with reduced doses at initiation. They presented fewer toxicities - irrespective of grade and type - than patients who received standard treatment (p<0.001) and had comparable overall survival (Log rank p=0.21). CONCLUSION: This is one of the first studies to highlight the value in conducting CMR and a CGA simultaneously before initiating systemic treatment in older patients with cancer. These two evaluations could give oncologists decisive information to personalize cancer treatment of older patients and optimize treatment dose to offer the best efficacy and minimize toxicity.

Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France.

BACKGROUND: In France, the combination hydroxychloroquine (HCQ) and azithromycin (AZ) is used in the treatment of COVID-19. METHODS: We retrospectively report on 1061 SARS-CoV-2 positive tested patients treated for at least three days with the following regimen: HCQ (200 mg three times daily for ten days) + AZ (500 mg on day 1 followed by 250 mg daily for the next four days). Outcomes were death, clinical worsening (transfer to ICU, and >10 day hospitalization) and viral shedding persistence (>10 days). RESULTS: A total of 1061 patients were included in this analysis (46.4% male, mean age 43.6 years - range 14-95 years). Good clinical outcome and virological cure were obtained in 973 patients within 10 days (91.7%). Prolonged viral carriage was observed in 47 patients (4.4%) and was associated to a higher viral load at diagnosis (p < .001) but viral culture was negative at day 10. All but one, were PCR-cleared at day 15. A poor clinical outcome (PClinO) was observed for 46 patients (4.3%) and 8 died (0.75%) (74-95 years old). All deaths resulted from respiratory failure and not from cardiac toxicity. Five patients are still hospitalized (98.7% of patients cured so far). PClinO was associated with older age (OR 1.11), severity of illness at admission (OR 10.05) and low HCQ serum concentration. PClinO was independently associated with the use of selective beta-blocking agents and angiotensin II receptor blockers (p < .05). A total of 2.3% of patients reported mild adverse events (gastrointestinal or skin symptoms, headache, insomnia and transient blurred vision). CONCLUSION: Administration of the HCQ+AZ combination before COVID-19 complications occur is safe and associated with a very low fatality rate in patients.