Impact of lymphopenia on efficacy of nivolumab in head and neck cancer patients

International audienceAbstractIntroductionLymphopenia has been correlated with poorer survival in patients with metastatic cancers treated with anti-PD-1 immunotherapy. Treatments such as chemotherapy, surgery or radiotherapy can induce lymphopenia. Radiation-induced lymphopenia is common and prolonged in head and neck cancer (HNSCC) patients. We evaluated the impact of lymphopenia, on efficacy of anti PD-1 nivolumab immunotherapy in HNSCC patients.MethodsA multicenter retrospective study included consecutive patients treated with nivolumab for recurrent/metastatic (R/M) HNSCC between January 2017 and June 2019. Lymphopenia was defined as lymphocyte counts below 1000 cells/mm3 upon initiation of nivolumab. Logistical regression was performed on factors associated with lymphopenia and ROC analyses assessed association between lymphopenia and survival.Resultsmedian age was 65. Of the 100 included patients, 60% had been treated by surgery, 67% had had first-line chemotherapy, and 89% loco-regional radiotherapy, 65% had concurrent chemotherapy with radiotherapy. Lymphopenia occurred in 56 (56%) patients upon initiation of nivolumab, with 29 (29%) patients having radiation-related lymphopenia. Prior locoregional radiotherapy was the only factor associated with lymphopenia upon initiation of nivolumab by logistical regression (OR 0.144 [0.029–0.706], p − 0.017). Lymphopenia upon initiation of nivolumab did not affect progression-free survival (PFS) (p − 0.815), overall survival (OS) (p − 0.783) or disease control rate (DCR) (p − 0.125). Locoregional symptomatology (HR − 2.37 [1.24–4.54], p − 0.009), metastatic symptomatology (HR − 4.74 [2.21–10.15], and persistent lymphopenia under nivolumab (HR 3.96 [1.19–13.17] p − 0.034) were associated with poorer OS in multivariate analysis.ConclusionsLymphopenia upon initiation of nivolumab was not associated with poorer survival in R/M HNSCC patients, but persistence of lymphopenia during immunotherapy might be a prognostic marker of patient survival

Bomarea pastazensis (Alstroemeriaceae), an exceptionally small new species from the eastern Andean slopes of Ecuador

Recent field research on the eastern slopes of the Andes resulted in the discovery of a new species of Bomarea from the Cerro Candelaria Reserve in the Tungurahua province of Ecuador. Bomarea pastazensis is the second smallest species in the genus and differs from the smallest by the presence of glutinous trichomes on the ovary, glabrous sepals, and greenish-yellow petals with purple spots. Based on IUCN guidelines, a preliminary conservation status is assigned as Vulnerable (VU)

Impact of electronic cigarettes on the oral cavity: scoping review

Esta revisão de escopo busca realizar um mapeamento global da literatura acerca dos impactos do cigarro eletrônico na cavidade oral. Nesse estudo, estudos piloto, quasi experimentais, estudos in-vitro, estudos controlados randomizados, estudos controlados e não randomizados e relato de caso serão incluídos sem restrições sobre o tipo de estudo, ano de publicação ou linguagem

Nutrient digestibility in horses of tropical grasses found in semi-arid areas of the Brazilian Northeast region assessed using mobile bags

ABSTRACT The present study used mobile bags to estimate horse nutrient digestibility of tropical grasses found in semi-arid areas of the Brazilian Northeast region. Five female mixed-breed horses with a mean weight of 400±23 kg were assigned to a 5×5 Latin square design with five periods of seven days and five grasses: Tifton 85 hay ( Cynodon spp. ), sixweeks threeawn ( Aristida adscensionis Linn.), Alexandergrass ( Brachiaria plantaginea (Link) Hitchc), capim-de-raiz ( Chloris orthonoton Doell), and Sabi grass ( Urochloa mosambicensis ). The nutrient content of forages was determined prior to inoculation in horses and after recovery of mobile bags from feces. The digestibility coefficients were determined from the difference between the inoculated and recovered material. The dry matter, organic matter, mineral matter, crude protein, neutral detergent fiber, and acid detergent fiber contents of the grass species were analyzed. Digestibility data were subjected to analysis of variance using the Statistical Analysis System (SAS, version 9.0) software. Higher dry matter digestibility coefficients were observed in Tifton 85 (74.61%), Alexandergrass (74.30%), and capim-de-raiz (68.88%) than in sixweeks threeawn (48.40%) and Sabi grass (52.89%). The highest crude protein digestibility coefficients were found for Alexandergrass (95.70%), Tifton 85 (93.50%), and sixweeks threeawn (93.35%). Sixweeks threeawn had lower apparent mineral matter digestibility than the other grasses. The digestibility coefficients of Alexandergrass and capim-de-raiz indicate that those grasses have potential to be used in equine feed.</div

The TRIPLEX study: use of patient-derived tumor organoids as an innovative tool for precision medicine in triple-negative breast cancer

Abstract 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

ORGAVADS: establishment of tumor organoids from head and neck squamous cell carcinoma to assess their response to innovative therapies

Abstract 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. </jats:sec