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BACKGROUND: Patients with breast cancer (BC) exhibit circadian rhythm disruptions, mainly of rest-activity rhythm (RAR), of which sleep is an essential component, and cortisol rhythm. Sleep complaints such as insomnia and cognitive impairments are prevalent in BC. In general population, sleep is known to contribute greatly to cognition. Thus, improving RAR (and particularly sleep) could help limiting cognitive impairments in BC patients. It has recently been suggested that, in addition to its essential role in spatial memory, the vestibular system contributes to RAR synchronization. Its stimulation could therefore limit both sleep disturbances and spatial memory deficits in BC. OBJECTIVES: The main aim of the ICANSLEEP-2 study is to assess the effects of galvanic vestibular stimulation (GVS) on circadian rhythms. The secondary aim is to assess whether GVS improves sleep and spatial memory in BC patients. METHODS: Two groups with insomnia complaints (Insomnia Severity Index > 7) will be included: a patients' group with BC (n = 50) and a healthy control group without history of cancer (n = 25). There will be two assessment sessions, before and after 2 weeks of GVS. Patients will be randomly assigned to either a GVS group or a sham group (noneffective stimulation). Controls will receive GVS. GVS effects will be quantified and compared between groups. Assessments will include actigraphy, salivary cortisol, polysomnography, a cognitive test battery (including a computer-based task for spatial memory) and validated questionnaires (for psychological functioning and sleep complaints). DISCUSSION: Current methods for improving sleep in BC have had controversial outcomes regarding sleep structure. We expect GVS to offer a new mean of directly targeting RAR disruptions in BC patients, with beneficial effects on sleep structure. Given the crucial impact of sleep on cognitive functioning, notably spatial memory, improving sleep of BC patients should enhance their cognitive functioning. ETHICS AND DISSEMINATION: This study received ethical approval from the Ile de France IV institutional review board on 19 April 2022 (no. ID-RCB: 2022-A00437-36). The findings yielded by this protocol will be presented at various conferences and in peer-reviewed journals. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT05414357.
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Neoplasias de la Mama , Ritmo Circadiano , Sueño , Memoria Espacial , Humanos , Neoplasias de la Mama/complicaciones , Femenino , Ritmo Circadiano/fisiología , Memoria Espacial/fisiología , Sueño/fisiología , Persona de Mediana Edad , Adulto , Vestíbulo del Laberinto/fisiopatología , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatología , Terapia por Estimulación Eléctrica/métodosRESUMEN
Objective: This multicenter study aimed to retrospectively evaluate the impact of high boost simultaneous integrated boost (SIB) to pathologic lymph nodes compared to Sequential boost (Seq) in patients with locally advanced cervical cancer (LACC). Materials and methods: 97 patients with pelvic and/or para-aortic (PAo) node-positive LACC treated by definitive chemoradiation were included. Two groups were analyzed: Sequential boost group and simultaneous integrated boost (SIB) group. Endpoints were Distant Recurrence Free Survival (DRFS), Recurrence Free Survival (RFS), Overall Survival (OS), locoregional pelvic and PAo control and toxicities. Results: 3-years DRFS in SIB and Seq groups was 65% and 31% respectively (log-rank p < 0.001). 3-years RFS was 58% and 26% respectively (log-rank p = 0.009). DRFS prognostic factors in multivariable analysis were SIB, PAo involvement and maximum pelvic node diameter ≥ 2cm. Adenocarcinoma histology and absence of brachytherapy tended to be prognostic factors. SIB provided the best pelvic control at first imaging with 97%. There was no significant difference in terms of toxicities between groups. Conclusions: Nodal SIB seems to be unavoidable in the treatment of node-positive LACC. It provides the best DRFS, RFS and pelvic control without additional toxicity, with a shortened treatment duration.
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Importance: Whether F18-choline (FCH) positron emission tomographic (PET)/computed tomographic (CT) scan can replace Tc99m-sestaMIBI (MIBI) single-photon emission (SPE)CT/CT as a first-line imaging technique for preoperative localization of parathyroid adenomas (PTA) in patients with primary hyperparathyroidism (PHPT) is unclear. Objective: To compare first-line FCH PET/CT vs MIBI SPECT/CT for optimal care in patients with PHPT needing parathyroidectomy and to compare the proportions of patients in whom the first-line imaging method resulted in successful minimally invasive parathyroidectomy (MIP) and normalization of calcemia 1 month after surgery. Design, Setting, and Participants: A French multicenter randomized open diagnostic intervention phase 3 trial was conducted. Patients were enrolled from November 2019 to May 2022 and participated up to 6 months after surgery. The study included adults with PHPT and an indication for surgical treatment. Patients with previous parathyroid surgery or multiple endocrine neoplasia type 1 (MEN1) were ineligible. Interventions: Patients were assigned in a 1:1 ratio to receive first-line FCH PET/CT (FCH1) or MIBI SPECT/CT (MIBI1). In the event of negative or inconclusive first-line imaging, they received second-line FCH PET/CT (FCH2) after MIBI1 or MIBI SPECT/CT (MIBI2) after FCH1. All patients underwent surgery under general anesthesia within 12 weeks following the last imaging. Clinical and biologic (serum calcemia and parathyroid hormone levels) assessments were performed 1 and 6 months after surgery. Main Outcomes and Measures: The primary outcome was a true-positive first-line imaging-guided MIP combined with uncorrected serum calcium levels of 2.55 mmol/l or less 1 month after surgery, corresponding to the local upper limit of normality. Results: Overall, 57 patients received FCH1 (n = 29) or MIBI1 (n = 28). The mean (SD) age of patients was 62.8 (12.5) years with 15 male (26%) and 42 female (74%) patients. Baseline patient characteristics were similar between groups. Normocalcemia at 1 month after positive first-line imaging-guided MIP was observed in 23 of 27 patients (85%) in the FCH1 group and 14 of 25 patients (56%) in the MIBI1 group. Sensitivity was 82% (95% CI, 62%-93%) and 63% (95% CI, 42%-80%) for FCH1 and MIBI1, respectively. Follow-up at 6 months with biochemical measures was available in 43 patients, confirming that all patients with normocalcemia at 1 month after surgery still had it at 6 months. No adverse events related to imaging and 4 adverse events related to surgery were reported. Conclusions: This randomized clinical trial found that first-line FCH PET/CT is a suitable and safe replacement for MIBI SPECT/CT. FCH PET/CT leads more patients with PHPT to correct imaging-guided MIP and normocalcemia than MIBI SPECT/CT thanks to its superior sensitivity. Trial Registration: ClinicalTrials.gov Identifier: NCT04040946.
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Colina , Hiperparatiroidismo Primario , Paratiroidectomía , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Tecnecio Tc 99m Sestamibi , Humanos , Femenino , Masculino , Hiperparatiroidismo Primario/cirugía , Hiperparatiroidismo Primario/diagnóstico por imagen , Hiperparatiroidismo Primario/sangre , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Paratiroidectomía/métodos , Anciano , Radioisótopos de Flúor , Neoplasias de las Paratiroides/cirugía , Neoplasias de las Paratiroides/diagnóstico por imagen , Neoplasias de las Paratiroides/complicaciones , Adenoma/cirugía , Adenoma/diagnóstico por imagenRESUMEN
BACKGROUND: Elderly cancer patients often experience cognitive difficulties that can affect their quality of life and autonomy. However, they are rarely included in clinical trials, and only one study has explored the feasibility of cognitive training in this population. While digital cognitive training has been successful in improving cognition in younger patients, its feasibility in elderly patients requires evaluation. OBJECTIVES: This feasibility study primarily focused on evaluating patients' ability to use digital cognitive stimulation (usability). Secondary objectives were to evaluate acceptability, adherence, and satisfaction with regard to digital cognitive stimulation in elderly breast cancer patients. METHODS: Elderly breast cancer patients at least 70 years old who were receiving cancer treatment (chemotherapy, targeted therapy, and/or radiotherapy) were recruited. Cognitive complaints were evaluated at baseline using the Functional Assessment of Cancer Therapy-Cognitive Function scale (FACT-Cog). Participants were invited to attend three 20-minute sessions of digital cognitive stimulation using HappyNeuron PRESCO software App on tablets, with the first session being supervised by a neuropsychologist and the two others being performed independently either at home or at the cancer center. We hypothesized that participants would spend 10 of the 20 min of the given time with the tablet completing exercises (training time). Thus, the usability of digital cognitive stimulation was defined as completing at least three exercises during the training time (10 min) of one of the two training sessions in autonomy. The proportion of patients who agreed to participate (acceptability) and completion of planned sessions (adherence) were also estimated. Satisfaction was evaluated post-intervention through a self-report questionnaire. RESULTS: 240 patients were initially screened, 60% (n = 145) were eligible and 38% agreed to participate in the study. Included patients (n = 55) had a mean age of 73 ± 3 years, 96% an ECOG score of 0-1 and were undergoing radiotherapy (64%), and/or chemotherapy (47%) and/or targeted therapy (36%) for stage I-II breast cancer (79%). Most patients reported significant cognitive complaints (82%) and 55% had previous experience with digital tools (n = 30). The usability rate was 92%, with 46 out of 50 evaluable participants completing at least three exercises during the training time. The adherence rate was 88%, with 43/50 participants completing all planned sessions. Participants were largely satisfied with the cognitive intervention format (87%). They preferred to complete sessions at the cancer center under the supervision of the neuropsychologist than alone at home (90%). CONCLUSIONS: The high level of usability, adherence and satisfaction in this study shows for the first time the feasibility of digital cognitive stimulation in cancer patients older than 70 years. However, the intervention should be proposed only to patients reporting cognitive complaints and should be structured and supervised to improve acceptability and adherence. TRIAL REGISTRATION: ClinicalTrials identifier: NCT04261153, registered on 07/02/2020.
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Neoplasias de la Mama , Estudios de Factibilidad , Humanos , Neoplasias de la Mama/terapia , Femenino , Anciano , Anciano de 80 o más Años , Satisfacción del Paciente , Terapia Cognitivo-Conductual/métodos , Aplicaciones Móviles , Calidad de VidaRESUMEN
BACKGROUND: Many patients treated for breast cancer (BC) complain about cognitive difficulties affecting their daily lives. Recently, sleep disturbances and circadian rhythm disruptions have been brought to the fore as potential contributors to cognitive difficulties in patients with BC. Yet, studies on these factors as well as their neural correlates are scarce. The purpose of the ICANSLEEP-1 (Impact of SLEEP disturbances in CANcer) study is to characterize sleep using polysomnography and its relationship with the evolution of cognitive functioning at both the behavioral and the neuroanatomical levels across treatment in BC patients treated or not with adjuvant chemotherapy. METHODS: ICANSLEEP-1 is a longitudinal study including BC patients treated with adjuvant chemotherapy (n = 25) or not treated with adjuvant chemotherapy (n = 25) and healthy controls with no history of BC (n = 25) matched for age (45-65 years old) and education level. The evaluations will take place within 6 weeks after inclusion, before the initiation of chemotherapy (for BC patients who are candidates for chemotherapy) or before the first fraction of radiotherapy (for BC patients with no indication for chemotherapy) and 6 months later (corresponding to 2 weeks after the end of chemotherapy). Episodic memory, executive functions, psychological factors, and quality of life will be assessed with validated neuropsychological tests and self-questionnaires. Sleep quantity and quality will be assessed with polysomnography and circadian rhythms with both actigraphy and saliva cortisol. Grey and white matter volumes, as well as white matter microstructural integrity, will be compared across time between patients and controls and will serve to further investigate the relationship between sleep disturbances and cognitive decline. DISCUSSION: Our results will help patients and clinicians to better understand sleep disturbances in BC and their relationship with cognitive functioning across treatment. This will aid the identification of more appropriate sleep therapeutic approaches adapted to BC patients. Improving sleep in BC would eventually help limit cognitive deficits and thus improve quality of life during and after treatments. TRIAL REGISTRATION: NCT05414357, registered June 10, 2022. PROTOCOL VERSION: Version 1.2 dated March 23, 2022.
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Neoplasias de la Mama , Anciano , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante/efectos adversos , Ritmo Circadiano , Cognición , Estudios Longitudinales , Calidad de Vida , Sueño , Estudios de Casos y ControlesRESUMEN
INTRODUCTION: The Coronavirus (COVID-19) pandemic and its associated health restrictions have harmed the population psychologically. We aimed to compare the post-traumatic stress disorder (PTSD) symptoms and Quality of Life (QoL) in older French patients with cancer to the younger ones. MATERIALS AND METHODS: This longitudinal multicenter study named COVIPACT began in April 2020 during the first French lockdown and has included 579 outpatients receiving treatment for a solid or hematological malignancy. Data were collected every three months, namely at the first release period (M3), at the second lockdown (M6), at the second release period (M9), and finally at the last curfew period (M12) in France. Standardized validated self-questionnaires were used to assess PTSD symptoms (using the Event Scale-Revised self-questionnaire), insomnia (through the Insomnia Severity Index questionnaire), QoL (using the Functional Assessment of Cancer Therapy - General questionnaire), and cognitive complaints (through the Functional Assessment of Cancer Therapy - Cognition questionnaire). Student (or Wilcoxon) tests and Chi-squared tests were used for continuous or discrete variables, respectively. We conducted linear mixed model to study the change during follow-up. RESULTS: Out of 579 included patients, 157 (27%) were ≥ 70 years old at baseline, of whom 104 participated in the longitudinal study. At baseline, older patients reported fewer PTSD symptoms (17% versus 23%, p = .06), insomnia (17% versus 27%, p = .02), and cognitive complaint (3% versus 16%, p < .01) than younger patients. QoL at baseline was similar between age subgroups. We observed no significant difference in the trajectory of PTSD symptoms, insomnia, or emotional well-being between both groups during the follow-up. Cognitive complaints were lower at baseline in older patients but steadily increased during the follow-up and reached the same level as younger patients at one year. DISCUSSION: One in five older patients reported PTSD symptoms, evolving similarly to younger patients during the first year of the COVID-19 pandemic. While cognitive complaints tend to recover in a bell-shaped curve at one year in younger patients, the trend is increasing in older ones. Screening for PTSD symptoms and late cognitive impairment should be given special attention in older patients. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04366154.
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COVID-19 , Neoplasias , Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos por Estrés Postraumático , Humanos , Anciano , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/psicología , Calidad de Vida/psicología , Pandemias , COVID-19/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Estudios Longitudinales , Control de Enfermedades Transmisibles , Neoplasias/terapiaRESUMEN
BACKGROUND: Triple negative breast cancers (TNBC) account for approximately 15% of all breast cancers and are associated with a shorter median survival mainly due to locally advanced tumor and high risk of metastasis. The current neoadjuvant treatment for TNBC consists of a regimen of immune checkpoint blocker and chemotherapy (chemo-ICB). Despite the frequent use of this combination for TNBC treatment, moderate results are observed and its clinical benefit in TNBC remains difficult to predict. Patient-derived tumor organoids (PDTO) are 3D in vitro cellular structures obtained from patient's tumor samples. More and more evidence suggest that these models could predict the response of the tumor from which they are derived. PDTO may thus be used as a tool to predict chemo-ICB efficacy in TNBC patients. METHOD: The TRIPLEX study is a single-center observational study conducted to investigate the feasibility of generating PDTO from TNBC and to evaluate their ability to predict clinical response. PDTO will be obtained after the dissociation of biopsies and embedding into extra cellular matrix. PDTO will be cultured in a medium supplemented with growth factors and signal pathway inhibitors. Molecular and histological analyses will be performed on established PDTO lines to validate their phenotypic proximity with the original tumor. Response of PDTO to chemo-ICB will be assessed using co-cultures with autologous immune cells collected from patient blood samples. PDTO response will finally be compared with the response of the patient to evaluate the predictive potential of the model. DISCUSSION: This study will allow to assess the feasibility of using PDTO as predictive tools for the evaluation of the response of TNBC patients to treatments. In the event that PDTO could faithfully predict patient response in clinically relevant time frames, a prospective clinical trial could be designed to use PDTO to guide clinical decision. This study will also permit the establishment of a living biobank of TNBC PDTO usable for future innovative strategies evaluation. TRIAL REGISTRATION: The clinical trial (version 1.2) has been validated by local research ethic committee on December 30th 2021 and registered at ClinicalTrials.gov with the identifier NCT05404321 on June 3rd 2022, version 1.2.
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Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Medicina de Precisión , Estudios Prospectivos , Organoides , BiopsiaRESUMEN
BACKGROUND: Non-metastatic breast cancer treatment is mainly based on surgery, with or without chemotherapy, radiotherapy and/or hormone therapy. To reduce the risk of hormone receptor positive (HR+) disease recurrence, hormone therapy is prescribed for at least 5 years. It may induce adverse drug reactions (ADRs) as joint pain, sexual dysfunction, weight increase, fatigue, mood disorders and vasomotor symptoms. Around 30-40% of patients withhold hormone therapy within 5 years after initiation. Based on encouraging results of mobile health in patient follow-up, we developed a web-application addressed for breast cancer patients initiating adjuvant hormonal therapy and aimed to assess its impact on hormone therapy adherence, ADRs management, and health-related quality of life. METHODS: The WEBAPPAC trial is a randomized, open-label, prospective, single-center phase 3 study aiming to assess the interest of a web-application support as compared to standard management among breast cancer patients initiating hormone therapy. The main endpoint is the proportion of patients with hormone therapy adherence failure within 18 months after treatment start, in each arm. Eligible patients will be 1:1 randomized between the WEBAPPAC web-application support (experimental arm,) or standard support (control arm), with stratification on type of hormone therapy (Aromatase inhibitor or Tamoxifen). We plan to enroll 438 patients overall. Failure to hormone therapy will be assessed using the Morisky 8-item self-questionnaire (MMSA8), patient adherence logbook, and medical consultations. Secondary outcomes include hormone therapy adherence at 6 months, pain (Visual Analogue Scale and Brief Pain Inventory), quality of life (EORTC QLQ-C30 and BR23 self-questionnaires), anxiety and depression (Hospital and Depression Scale), and return to work and/or daily activities. The user experience with the WEBAPPAC web-application will be assessed using the System Usability Scale (SUS) questionnaire. DISCUSSION: Hormone therapy discontinuation or adherence failure in breast cancer patients may be indirectly related to an increased risk of recurrence. A better control of medication adherence, through the detection of side effects and some proposed actions trying to reduce them, appears therefore essential to limit the risk of disease recurrence. The WEBAPPAC web-application thus aims better monitoring and allowing higher level of responsiveness in case of ADRs, thus improving treatment adherence. TRIAL REGISTRATION: NCT04554927, registered September 18, 2020. PROTOCOL VERSION: Version 2.1 dated from December 21, 2021.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Calidad de Vida , Estudios Prospectivos , Recurrencia Local de Neoplasia , Cumplimiento de la Medicación , Adyuvantes Inmunológicos/uso terapéutico , Hormonas/uso terapéutico , DolorRESUMEN
INTRODUCTION: COVID-19 outbreak rapidly spread since early 2020 leading to the implementation of nationwide lockdowns. To cope with this sudden change, management guidelines were quickly published to adapt oncological care, with potential impact on cancer outcomes. METHODS: We conducted a retrospective comparative cohort study to assess the impact of the COVID-19 outbreak in 2020 on cancer outcomes in metastatic patients. Two cohorts of metastatic patients receiving intravenous (iv) therapy in a French oncological day care hospital were assessed: a 2020 cohort during the first French lockdown, and a 2018 historical cohort before the COVID-19 pandemic. We performed a propensity score analysis to match patients from the two cohorts. After one-year follow-up, we compared progression-free survival (PFS) and overall survival (OS) between cohorts. Adaptations of medical oncological treatments in 2020 were also analysed. RESULTS: The 376 patients of the 2020 cohort were matched with 376 of the 2018 cohort. No SARS-CoV-2 infection was observed in the 2020 cohort. The adjusted PFS was significantly shorter in 2020 compared to 2018 (HR = 1.23; 95% CI: 1.03-1.46), as well as among patients without treatment adaptation compared to matched patients of the 2018 cohort (HR = 1.33; 95% CI: 1.10-1.61). We did not observe any significant difference of PFS among the group with treatment adaptations. OS was not significantly different. CONCLUSION: Metastatic cancer patients treated during the first lockdown had a higher risk of disease progression 1 year after COVID-19 outbreak. However, oncological treatment adaptations or SARS-CoV-2 infections do not explain these results. A longer follow-up is needed to observe the impact on OS.
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BACKGROUND: Radiotherapy is one of the cornerstones of the treatment of Head and Neck Squamous Cell Carcinomas (HNSCC). However, radioresistance is associated with a high risk of recurrence. To propose strategies (such as combinations with drugs) that could over intrinsic radioresistance, it is crucial to predict the response to treatment. Patient-Derived Tumor Organoids (PDTO) are in vitro tridimensional microtumors obtained from patient' own cancer samples. They have been shown to serve as reliable surrogates of the tumor response in patients. METHODS: The ORGAVADS study is a multicenter observational trial conducted to investigate the feasibility of generating and testing PDTO derived from HNSCC for the evaluation of sensitivity to treatments. PDTO are obtained after dissociation of resected tumors remaining from tissues necessary for the diagnosis. Embedding of tumor cells is then performed in extracellular matrix and culture in medium supplemented with growth factors and inhibitors. Histological and immunohistochemical characterizations are performed to validate the resemblance between PDTO and their original tumor. Response of PDTO to chemotherapy, radiotherapy and innovating combinations are assessed, as well as response to immunotherapy using co-cultures of PDTO with autologous immune cells collected from patient blood samples. Transcriptomic and genetic analyses of PDTO allow validation of the models compared to patients' own tumor and identification of potential predictive biomarkers. DISCUSSION: This study is designed to develop PDTO models from HNSCC. It will allow comparing the response of PDTO to treatment and the clinical response of the patients from whom they are derived. Our aim is to study the PDTO ability to predict the clinical response to treatment for each patient in view of a personalized medicine as well as to establish a collection of HNSCC models that will be useful for future innovative strategies evaluation. TRIAL REGISTRATION: NCT04261192, registered February 7, 2020, last amendment v4 accepted on June, 2021.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/patología , Terapias en Investigación , Organoides/patologíaRESUMEN
BACKGROUND: Patients with cancer may be particularly vulnerable to psychological consequences of the COVID-19 pandemic. We studied the prevalence and evolution of posttraumatic stress symptoms (PTSS) in patients with cancer during the pandemic waves, and we investigated factors associated with high symptoms. METHODS: COVIPACT is a 1-year longitudinal prospective study of French patients with solid/hematologic malignancies receiving treatment during the first nationwide lockdown. PTSS were measured every 3 months from April 2020 using the Impact of Event Scale-Revised. Patients also completed questionnaires on their quality of life, cognitive complaints, insomnia, and COVID-19 lockdown experience. RESULTS: Longitudinal analyses involved 386 patients with at least one PTSS assessment after baseline (median age, 63 years; 76% female). Among them, 21.5% had moderate/severe PTSS during the first lockdown. The rate of patients reporting PTSS decreased at lockdown release (13.6%), increased again at second lockdown (23.2%), and slightly declined from the second release period (22.7%) to the third lockdown (17.5%). Patients were grouped into 3 trajectories of evolution. Most patients had stable low symptoms throughout the period, 6% had high baseline symptoms slowly decreasing over time, and 17.6% had moderate symptoms worsening during the second lockdown. Female sex, feeling socially isolated, worrying about COVID-19 infection, and using psychotropic drugs were associated with PTSS. PTSS were associated with impaired quality of life, sleep, and cognition. CONCLUSIONS: Approximately one-fourth of patients with cancer experienced high and persistent PTSS over the first year of the COVID-19 pandemic and may benefit from psychological support. CLINICALTRIALS: gov identifier: NCT04366154.
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COVID-19 , Neoplasias , Trastornos por Estrés Postraumático , Femenino , Humanos , Masculino , Persona de Mediana Edad , Control de Enfermedades Transmisibles , COVID-19/epidemiología , Estudios Longitudinales , Neoplasias/epidemiología , Pandemias , Estudios Prospectivos , Calidad de Vida/psicología , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/psicologíaRESUMEN
BACKGROUND: Previous reports showed limited efficacy of immune checkpoint inhibitors as single-agent treatment for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation or ALK/ROS1 fusion. We aimed at evaluating the efficacy and safety of immune checkpoint inhibitor combined with chemotherapy and bevacizumab (when eligible) in this patient subgroup. METHODS: We conducted a French national open-label multicentre non-randomised non-comparative phase II study in patients with stage IIIB/IV NSCLC, oncogenic addiction (EGFR mutation or ALK/ROS1 fusion), with disease progression after tyrosine kinase inhibitor and no prior chemotherapy. Patients received platinum, pemetrexed, atezolizumab, bevacizumab (PPAB cohort) or, if not eligible to bevacizumab, platinum-pemetrexed-atezolizumab (PPA cohort). The primary end-point was the objective response rate (RECIST v1.1) after 12 weeks, evaluated by blind independent central review. RESULTS: 71 patients were included in PPAB cohort and 78 in PPA cohort (mean age, 60.4/66.1 years; women 69.0%/51.3%; EGFR mutation, 87.3%/89.7%; ALK rearrangement, 12.7%/5.1%; ROS1 fusion, 0%/6.4%, respectively). After 12 weeks, objective response rate was 58.2% (90% confidence interval [CI], 47.4-68.4) in PPAB cohort and 46.5% (90% CI, 36.3-56.9) in PPA cohort. Median progression-free survival and overall survival were 7.3 (95% CI 6.9-9.0) months and 17.2 (95% CI 13.7-NA) months in PPAB cohort and 7.2 (95% CI 5.7-9.2) months and 16.8 (95% CI 13.5-NA) months in PPA cohort, respectively. Grade 3-4 adverse events occurred in 69.1% of patients in PPAB cohort and 51.4% in PPA cohort; Grade 3-4 atezolizumab-related adverse events occurred in 27.9% and 15.3%, respectively. CONCLUSION: Combination approach with atezolizumab with or without bevacizumab and platinum-pemetrexed achieved promising activity in metastatic EGFR-mutated or ALK/ROS1-rearranged NSCLC after tyrosine kinase inhibitor failure, with acceptable safety profile.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Femenino , Humanos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Pemetrexed , Platino (Metal)/uso terapéutico , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genéticaRESUMEN
BACKGROUND: Urothelial carcinoma (UC) is the ninth most commonly diagnosed cancer worldwide, with a 3.8/1 male to female ratio. Platinum-based chemotherapy is the first line standard of care for fit patients with advanced UC. However, despite a response rate (RR) for approximately half of patients receiving standard chemotherapy, durable responses are rare (median progression-free progression (PFS) around 8 months). Recently, immune checkpoint inhibitors (ICI) have emerged as new therapeutic options. Among them, Avelumab, an anti-PD-L1 antibody, was assessed in maintenance treatment, demonstrating an overall survival improvement in the JAVELIN Bladder-100 phase III trial. These findings led to its approval as first line maintenance therapy for patients with locally advanced or metastatic UC who have not progressed on prior platinum-containing chemotherapy. However, disease progression as best response was noticed for 37% of patients under Avelumab as maintenance treatment. UC has targetable genomic alterations, including DNA damage repair (DDR) alterations. DDR deficiency is known to major sensitivity to both platinum-based chemotherapy and PD-1/PD-L1 blockade and the combination of ICI and PARP inhibitors showed promising results. It therefore warrants to assess the interest of combining ICI plus PARP inhibitors as maintenance treatment in UC patients. METHODS: The TALASUR trial is a single-arm multicenter phase 2 study aiming to assess the antitumor activity of the combination of Avelumab with Talazoparib among patients with locally advanced/metastatic UC in maintenance therapy after platinum-based chemotherapy. The primary objective is to determine the efficacy of the combination, assessed through PFS. Secondary objectives are as follows: safety profile of the association, objective response, duration of tumoral response, disease control rate, time to subsequent therapy, quality of life. A blood and tumor collections will be also constituted. Patient will receive the combination therapy of daily oral Talazoparib (1 mg/day) and intra-venous Avelumab 800 mg on days 1 and 15, in a 28-day cycle. Fifty patients will be enrolled. DISCUSSION: Talazoparib with Avelumab combination may have additive activity when administrated jointly. We hypothesize that combination will increase the antitumor activity in UC first line maintenance setting with an acceptable safety profile. TRIAL REGISTRATION: NCT04678362, registered December 21, 2020. PROTOCOL VERSION: Version 1.3 dated from 2020 09 11.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Femenino , Humanos , Masculino , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Platino (Metal)/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Calidad de Vida , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Introduction: We aimed to study post-traumatic stress disorder (PTSD) symptoms in breast cancer (BC) patients during the coronavirus disease (COVID-19) pandemic. Materials and methods: We included BC patients receiving medical treatment during the first COVID-19 lockdown in France. PTSD symptoms were evaluated using the Impact of Event Scale-Revised (IES-R) questionnaire. Quality of life [Functional Assessment of Cancer Therapy-General (FACT-G)], cognitive complaints [Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog)], insomnia [Insomnia Severity Index (ISI)], and psychosocial experiences during lockdown were also evaluated. Multivariable logistic regression was used to identify clinical factors (from medical records) and psychosocial factors (from questionnaires) associated with PTSD symptoms. Results: Among the 253 included BC patients (mean age: 58), 46% had metastatic cancer and 52% were treated by chemotherapy alone. COVID-19-induced adjustments in medical oncology practices were experienced by 27% of patients (mainly teleconsultations). No case of COVID-19 was reported; 23% of BC patients had PTSD symptoms. Compared to other patients, patients with PTSD symptoms had more fears relative to COVID-19 infection (83 vs. 60%, p = 0.009), had more feeling of isolation (69 vs. 41%, p = 0.003), and had more prescription or increased use of psychotropic drugs (49 vs. 20%, p = 0.001). In the multivariable model adjusted for clinical factors, fears relative to COVID-19 and increased use of psychotropic drugs were independently associated with PTSD symptoms (OR [95% CI] = 3.01 [1.20-8.44] and 3.45 [1.48-8.17], respectively). Besides, patients with PTSD symptoms had poor quality of life (QoL), and more cognitive complaints and insomnia. Conclusion: Post-traumatic stress disorder symptoms were observed in 23% of BC patients during the first COVID-19 lockdown in France. Psychological supports are needed for patients treated during the COVID-19 pandemic.
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Background: Previous studies have revealed both sleep alterations and prospective memory (PM) impairments in breast cancer (BC) patients. PM refers to memory of intended actions and is crucial for daily living tasks and treatment compliance. As sleep is known to favor memory consolidation, one may expect that changes in sleep quality related to BC would have an impact on PM performance. This study aimed at assessing sleep-dependent consolidation of intentions using an ecological, virtual reality-based PM task in BC patients not treated with chemotherapy. Materials and methods: Thirty-seven early stages BC patients and 21 healthy controls (HC) participated in this study. PM was assessed using a virtual reality task, during which participants learnt a list of intentions and recalled them after a retention interval filled with a day awake or a night of sleep monitored by polysomnography. Sleep spindles and slow waves, brain oscillations involved in sleep-dependent memory consolidation, were quantified automatically using the Aseega software (Physip). Subjective sleep disturbances and markers of quality of life (psychological distress, fatigue, and well-being) were assessed by questionnaires. Results: Greater PM performance was observed after sleep than after an equivalent period of daytime wakefulness for both groups (HC and BC). PM performance after sleep did not differ significantly between groups. Yet, BC patients reported greater sleep disturbances than HC which were related with poorer intentions retrieval, greater psychological distress, fatigue and poorer well-being. The frequency of spindles was higher and the amplitude of slow waves lower in BC patients compared to HC. However, no significant association was observed between polysomnography parameters and PM scores in the whole sample of participants. Conclusion: Although subtle changes in brain oscillations involved in sleep-dependent memory consolidation were observed, these changes did not significantly impair overnight PM consolidation in BC patients. Nevertheless, poorer PM performance was associated with greater sleep complaints which in turn were related to poorer quality of life. Overall, these data suggest that sleep-dependent PM consolidation mechanisms are not altered in early stages BC patients not treated with chemotherapy. Further investigations are needed to understand the association between markers of quality of life and sleep-dependent memory consolidation.
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Rest-activity rhythm (RAR) disruptions are frequently associated with chemotherapy in breast cancer (BC), but they are less known in BC with endocrine therapy (ET). The aim of this ancillary study was to characterize the RAR and estimated sleep characteristics from actigraphy in BC patients either treated (ET+) or untreated with ET (ET-), compared to healthy controls (HC) and using a cross-sectional design. Eighteen ET+, 18 ET-, and 16 HC completed questionnaires and wore wrist actigraphs at home for 2 weeks. Parametric and nonparametric RAR, sleep parameters, and quality of life were compared between groups (p < .05). BC groups presented lower daytime activity than HC according to RAR analysis (mesor and M10 parameters). Compared to HC, ET- had lower inter-daily stability and ET+ had greater sleep complaints. Compared to ET-, ET+ had lower sleep efficiency, more time awake, and higher activity levels at night, as assessed with actigraphy. Our results suggest an effect of cancer independent of treatment on RAR in BC, highlighting the need for further investigation of this topic. In contrast, sleep as assessed with actigraphy seems modified only during ET which matches with patients' sleep complaints. Further longitudinal studies would aid in confirming the latter hypothesis.
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Neoplasias de la Mama , Actigrafía/métodos , Neoplasias de la Mama/tratamiento farmacológico , Ritmo Circadiano , Estudios Transversales , Femenino , Humanos , Calidad de Vida , Descanso , SueñoRESUMEN
BACKGROUND: Germ cell tumors and sex cord stromal tumors are rare cancers of the ovary. They mainly affect young women and are associated with a high survival rate. The standard treatment mainly involves conservative surgery combined with chemotherapy [bleomycin, etoposide and cisplatin (BEP)] depending on the stage and the prognostic factors, as for testicular cancers. As reported in testicular cancer survivors, chemotherapy may induce sequelae impacting quality of life, which has not yet been evaluated in survivors of germ cell tumors and sex cord stromal tumors. The GINECO-VIVROVAIRE-Rare tumor study is a two-step investigation aiming to assess i) chronic fatigue and quality of life and ii) long-term side-effects of chemotherapy with a focus on cardiovascular and pulmonary disorders. METHODS: Using self-reported questionnaires, chronic fatigue and quality of life are compared between 134 ovarian cancer survivors (cancer-free ≥2 years after treatment) treated with surgery and chemotherapy and 2 control groups (67 ovarian cancer survivors treated with surgery alone and 67 age-matched healthy women). Medical data are collected from patient records. In the second step evaluating the long-term side-effects of chemotherapy, a subgroup of 90 patients treated with chemotherapy and 45 controls undergo the following work-up: cardiovascular evaluation (clinical examination, non-invasive cardiovascular tests to explore heart disease, blood tests), pulmonary function testing, audiogram, metabolic and hormonal blood tests. Costs of sequelae will be also assessed. Patients are selected from the registry of the INCa French Network for Rare Malignant Ovarian Tumors, and healthy women by the 'Seintinelles' connected network (collaborative research platform). DISCUSSION: This study will provide important data on the potential long-term physical side-effects of chemotherapy in survivors of Germ Cell Tumors (GCT) and Sex Cord Stromal Tumors (SCST), especially cardiovascular and pulmonary disorders, and neurotoxicity. The identification of long-term side-effects can contribute to adjusting the treatment of ovarian GCT or SCST patients and to managing follow-up with adapted recommendations regarding practices and chemotherapy regimens, in order to reduce toxicity while maintaining efficacy. Based on the results, intervention strategies could be proposed to improve the management of these patients during their treatment and in the long term. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov : 03418844 , on 1 February 2018. This trial was registered on 25 October 2017 under the unique European identification number (ID-RCB): 2017-A03028-45. Recruitment Status: Recruiting. PROTOCOL VERSION: Version n° 4.2 dated from Feb 19, 2021. TRIAL SPONSOR: Centre François Baclesse, 3 avenue du Général Harris, F-14076 Caen cedex 05, France.
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Síndrome de Fatiga Crónica/etiología , Neoplasias Ováricas/tratamiento farmacológico , Calidad de Vida/psicología , Estudios de Casos y Controles , Síndrome de Fatiga Crónica/patología , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Encuestas y Cuestionarios , Tasa de SupervivenciaRESUMEN
Cancer-related cognitive impairment (CRCI) is a frequent side-effect of cancer treatment, with important consequences on patients' quality of life. Cognitive stimulation and physical activity are the most efficient in improving cognitive impairment, but they are challenging to generalize in hospitals' routine and to patients' needs and schedules. Moreover, the added value of a combination of these interventions needs to be more investigated. The Cog-Stim study is an interventional study investigating the feasibility of a web-based multimodal intervention (combining cognitive stimulation and physical activity for the improvement of cognitive complaints among breast-cancer patients currently treated with radiotherapy (n = 20). Patients will take part in a 12-week program, proposing two sessions per week of web-based cognitive stimulation (20 min/session with HappyNeuron®) and two sessions per week of web-based physical activity (30 min/session with Mooven® platform). Cognitive complaints (FACT-Cog) and objective cognitive functioning (CNS Vital Signs®), anxiety, depression (HADS), sleep disorders (ISI) and fatigue (FACIT-Fatigue) will be assessed before and after the intervention. The primary endpoint is the adherence rate to the intervention program. Patients' satisfaction, reasons for non-attrition and non-adherence to the program will also be assessed. The overall goal of this study is to collect information to develop web-based interventions for cognitive difficulties in supportive care units.
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BACKGROUND: The COVID-19 pandemic may induce post-traumatic stress disorder (PTSD) symptoms among patients with cancer, who also face adaptations to their treatment. The authors assessed the occurrence of PTSD symptoms, investigated pandemic-induced adjustments in medical oncology practice in patients with cancer, and explored risk factors for PTSD and the association between PTSD symptoms, insomnia, and quality of life (QoL). METHODS: This prospective French study was conducted in patients with solid/hematologic tumors who were receiving medical treatment in the day care departments of 2 cancer centers during the lockdown. Adjustments to medical oncology practice were collected from medical records. PTSD (measured using the Impact of Event Scale-Revised), insomnia (measured using the Insomnia Severity Index), QoL (measured using the Functional Assessment of Cancer Therapy-General instrument), and cognitive complaints (measured using the Functional Assessment of Cancer Therapy-Cognitive Function instrument) were collected through validated questionnaires. RESULTS: Clinical data and questionnaires were available for 734 and 576 patients, respectively. The median patient age was 64 years, and 69% of patients were women. Twenty-one percent of patients had PTSD. Twenty-seven percent (95% CI, 23%-30%) had an adjustment in their medical oncology program, including adjournments (29%), treatment interruptions (16%), modified treatment plans (27%), or adapted monitoring (27%). Women and patients experiencing an adjustment in oncology practice had a higher odds of PTSD (odds ratio= 2.10 [95% CI, 1.07-4.14] and 1.65 [95% CI, 1.03-2.63]; P < .05). PTSD symptoms were correlated with worse scores for QoL, cognition, and insomnia. CONCLUSIONS: Twenty-one percent of patients with cancer experienced PTSD symptoms associated with poor QoL during the first COVID-19-induced lockdown. Medical oncology practice was adjusted in approximately one-quarter of patients and was associated with the occurrence of PTSD symptoms. Psychosocial support should be offered in cancer centers to promote emotional resilience and avoid PTSD symptoms in patients.
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COVID-19 , Centros de Día , Neoplasias , Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos por Estrés Postraumático , Adulto , COVID-19/psicología , Control de Enfermedades Transmisibles , Femenino , Francia , Hospitales , Humanos , Masculino , Oncología Médica , Persona de Mediana Edad , Neoplasias/epidemiología , Neoplasias/psicología , Pandemias , Estudios Prospectivos , Calidad de Vida , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Trastornos por Estrés Postraumático/epidemiologíaRESUMEN
BACKGROUND: The common endocrine disorder primary hyperparathyroidism (PHPT) can be cured by surgery. Preoperative localization of parathyroid adenoma (PTA) by imaging is a prerequisite for outpatient minimally invasive parathyroidectomy (MIP). Compared to inpatient bilateral cervical exploration (BCE) which is performed if imaging is inconclusive, MIP is superior in terms of cure and complication rates and less costly. The imaging procedure F18-choline (FCH) PET/CT outperforms Tc99m-sestaMIBI (MIBI) SPECT/CT for PTA localization, but it is much costlier. The aim of this study is to identify the most efficient first-line imaging modality for optimal patient care in PHPT without added cost to society. METHODS: We will conduct a multicenter open diagnostic intervention randomized phase III trial comparing two diagnostic strategies in patients with PHPT: upfront FCH PET/CT versus MIBI SPECT/CT. The primary endpoint is the proportion of patients in whom the first-line imaging method results in successful MIP and cure. Follow-up including biological tests will be performed 1 and 6 months after surgery. The main secondary endpoint is the social cost of both strategies. Other secondary endpoints are as follows: FCH PET/CT and MIBI SPECT/CT diagnostic performance, performance of surgical procedure and complication rate, FCH PET/CT inter- and intra-observer variability and optimization of FCH PET/CT procedure. Fifty-eight patients will be enrolled and randomized 1:1. DISCUSSION: FCH PET/CT is a highly efficient but expensive imaging test for preoperative PTA localization and costs three to four times more than MIBI SPECT/CT. Whether FCH PET/CT improves patient outcomes compared to the reference standard MIBI SPECT/CT is unknown. To justify its added cost, FCH PET/CT-guided parathyroid surgery should lead to improved patient management, resulting in higher cure rates and fewer BCEs and surgical complications. In the previous phase II APACH1 study, we showed that second-line FCH PET/CT led to a cure in 88% of patients with negative or inconclusive MIBI SPECT/CT. BCE could be avoided in 75% of patients and surgical complication rates were low. We therefore hypothesize that upfront FCH PET/CT would improve patient care in PHPT and that the reduction in clinical costs would offset the increase in imaging costs. TRIAL REGISTRATION: NCT04040946 , registered August 1, 2019. Protocol version Version 2.1 dated from 2020/04/23.