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Immune checkpoint therapy (ICT) has dramatically altered clinical outcomes for cancer patients and conferred durable clinical benefits, including cure in a subset of patients. Varying response rates across tumor types and the need for predictive biomarkers to optimize patient selection to maximize efficacy and minimize toxicities prompted efforts to unravel immune and non-immune factors regulating the responses to ICT. This review highlights the biology of anti-tumor immunity underlying response and resistance to ICT, discusses efforts to address the current challenges with ICT, and outlines strategies to guide the development of subsequent clinical trials and combinatorial efforts with ICT.
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Imunoterapia , Neoplasias , Humanos , Antígeno B7-H1 , Neoplasias/tratamento farmacológico , Ensaios Clínicos como Assunto , Inibidores de Checkpoint Imunológico/administração & dosagemRESUMO
Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for many cancer types. The clinical use of ICIs is increasing rapidly, including in combinations associated with increased risk of toxicities, termed "immune-related adverse events" (irAEs). Therefore, MD Anderson Cancer Center (MDACC) in Houston, Texas has proactively responded by developing a priority endeavor known as the Immuno-Oncology Toxicity (IOTOX) initiative. This strategic initiative aims to facilitate the seamless integration of key domains: (1) standardized clinical practice and innovative decision toolsets; (2) patient and provider education; and (3) a comprehensive clinical and translational research platform. The ultimate goal of this initiative is to develop and disseminate clinical best practices and biologic insights into irAEs to improve outcomes of patients with irAEs at MDACC and in the wider oncology community.
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Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/terapia , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Texas , Imunoterapia/métodos , Imunoterapia/efeitos adversosRESUMO
OPINION STATEMENT: Localized high-risk (HR) prostate cancer (PCa) is a heterogenous disease state with a wide range of presentations and outcomes. Historically, non-surgical management with radiotherapy and androgen deprivation therapy was the treatment option of choice. However, surgical resection with radical prostatectomy (RP) and pelvic lymph node dissection (PLND) is increasingly utilized as a primary treatment modality for patients with HRPCa. Recent studies have demonstrated that surgery is an equivalent treatment option in select patients with the potential to avoid the side effects from androgen deprivation therapy and radiotherapy combined. Advances in imaging techniques and biomarkers have also improved staging and patient selection for surgical resection. Advances in robotic surgical technology grant surgeons various techniques to perform RP, even in patients with HR disease, which can reduce the morbidity of the procedure without sacrificing oncologic outcomes. Clinical trials are not only being performed to assess the safety and oncologic outcomes of these surgical techniques, but to also evaluate the role of surgical resection as a part of a multimodal treatment plan. Further research is needed to determine the ideal role of surgery to potentially provide a more personalized and tailored treatment plan for patients with localized HR PCa.
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Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Antagonistas de Androgênios/uso terapêutico , Androgênios , Excisão de Linfonodo/métodos , Terapia Combinada , Prostatectomia/métodosRESUMO
INTRODUCTION: Paraneoplastic cerebellar degeneration (PCD) is a rare set of neurological disorders arising from tumor-associated autoimmunity against antigens within the cerebellum. Anti-Purkinje cell cytoplasmic antibody 1 (PCA-1), or anti-Yo, is the most commonly linked antibody and is classically associated with breast and ovarian cancers. METHODS: Medical records of patients at our institution who developed PCA-1 associated PCD were reviewed. Clinical information, including cancer history, cancer-directed treatment, and serum and CSF titers of PCA-1 antibody were extracted. CASES: We report a series of cases of PCA-1 associated PCD in patients with known breast or ovarian cancer diagnosis not receiving immunotherapy. These cases highlight aspects of PCA-1 paraneoplastic syndrome such as triggering by cytotoxic chemotherapy or surgery, the possibility of tumor recurrence and the association with development of a second cancer. DISCUSSION: Diagnosis of the syndrome requires neurological workup with lumbar puncture (LP) with cerebrospinal fluids (CSF) studies, serum and CSF paraneoplastic antibody panel, and neuroimaging. Inpatient admission for prompt workup and initiation of treatment is recommended. Treatment most commonly includes immunosuppression with corticosteroids, plasmapheresis, and/or intravenous immune globulin (IVIG); however, we postulate that other immune modulating treatments may warrant consideration. CONCLUSION: These cases highlight the need for early recognition of the syndrome in patients receiving nonimmune based chemotherapy, for prompt workup and treatment.
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Neoplasias Ovarianas , Degeneração Paraneoplásica Cerebelar , Anticorpos Antineoplásicos , Antígenos de Neoplasias , Autoanticorpos , Cerebelo , Feminino , Humanos , Recidiva Local de Neoplasia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/terapia , Degeneração Paraneoplásica Cerebelar/etiologia , Degeneração Paraneoplásica Cerebelar/terapiaRESUMO
Invagination of epithelial sheets to form furrows is a fundamental morphogenetic movement and is found in a variety of developmental events including gastrulation and vertebrate neural tube formation. The cephalic furrow is a deep epithelial invagination that forms during Drosophila gastrulation. In the first phase of cephalic furrow formation, the initiator cells that will lead invagination undergo apicobasal shortening and apical constriction in the absence of epithelial invagination. In the second phase of cephalic furrow formation, the epithelium starts to invaginate, accompanied by both basal expansion and continued apicobasal shortening of the initiator cells. The cells adjacent to the initiator cells also adopt wedge shapes, but only after invagination is well underway. Myosin II does not appear to drive apical constriction in cephalic furrow formation. However, cortical F-actin is increased in the apices of the initiator cells and in invaginating cells during both phases of cephalic furrow formation. These findings suggest that a novel mechanism for epithelial invagination is involved in cephalic furrow formation.
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Actinas/metabolismo , Encéfalo/embriologia , Forma Celular/fisiologia , Drosophila/embriologia , Epitélio/embriologia , Gastrulação/fisiologia , Morfogênese/fisiologia , Junções Aderentes/fisiologia , Animais , Encéfalo/ultraestrutura , Processamento de Imagem Assistida por Computador , Microscopia Confocal , Microscopia Eletrônica de Varredura , Imagem com Lapso de TempoRESUMO
Caffey disease, also referred to as infantile cortical hyperostosis, is a self-limiting inflammatory disease of bone, typically diagnosed in infancy (ages less than five months). This disease is characterized by asymmetric, often polyostotic bony hyperostosis and expansion, with a predilection for the mandible (70-90%). We present a unique case of a two-month-old boy with monostotic scapular hyperostosis. The disease is primarily diagnosed on plain film and further evaluated with bone scintigraphy or skeletal survey to identify the extent of osseous involvement. Accompanying MR imaging is not usually obtained due to lack of specificity and diagnostic utility, and when pursued, can potentially confound the diagnosis. MR findings of this case are presented to re-iterate the benignity of this disease process and obviate the need for further invasive procedures.
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Immune checkpoint therapies (ICT) can induce life-threatening immune-related adverse events, including myocarditis and myositis, which are rare but often concurrent. The molecular pathways and immune subsets underlying these toxicities remain poorly understood. To address this need, we performed single-cell RNA sequencing of heart and skeletal muscle biopsies obtained from living patients with cancers treated with ICTs and admitted to the hospital with myocarditis and/or myositis (overlapping myocarditis plus myositis, n = 10; myocarditis-only, n = 1) or ICT-exposed patients ruled out for toxicity utilized as controls (n = 9). All biopsies were obtained within 96 hours of clinical presentation. Analyses of 58,523 cells revealed CD8+ T cells with a cytotoxic phenotype expressing activation/exhaustion markers in both myocarditis and myositis. Furthermore, the analyses identified a population of myeloid cells expressing tissue-resident signatures and FcγRIIIa (CD16a), which is known to bind IgG and regulate complement activation. Immunohistochemistry of affected cardiac and skeletal muscle tissues revealed protein expression of pan-IgG and complement product C4d, which were associated with the presence of high-titer serum autoantibodies against muscle antigens in a subset of patients. We further identified a population of inflammatory IL1B+TNF+ myeloid cells specifically enriched in myocarditis and associated with greater toxicity severity and poorer clinical outcomes. These results provide insight into the myeloid subsets present in human immune-related myocarditis and myositis tissues and nominate new targets for investigation into rational treatments to overcome these high-mortality toxicities. See related Spotlight by Fankhauser et al., p. 954.
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Miocardite , Miosite , Humanos , Miocardite/imunologia , Miosite/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Idoso , Neoplasias/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Adulto , Receptores de IgG/metabolismo , Músculo Esquelético/imunologia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Análise de Célula ÚnicaRESUMO
BACKGROUND: Androgen signaling is central to prostate cancer and men's health. Prior data indicates that increasing body fat is unfavorable in the localized setting yet associated with favorable outcomes in men with metastatic disease. Understanding the biological links between adiposity and prostate cancer may optimize the therapeutic index with ASI. We hypothesized that host adiposity and androgen synthesis are linked to the efficacy and toxicity of ASI for men with metastatic castration-resistant prostate cancer (mCRPC). METHODS: A post-hoc analysis was done of NCT02703623 where men with mCRPC (n = 186) were treated for 8 weeks with abiraterone acetate, prednisone, and apalutamide (AAPA), and a satisfactory response was defined as a PSA decline >50%. Body composition was measured on baseline CT scans. Germline DNA WES was performed with a focus on variants in steroidogenic genes. Adipokine levels were measured in pre-treatment plasma. RESULTS: Germline polymorphisms in 3 genes involved in androgen synthesis (AKR1C3 rs12529, CYP17A1 rs6162, SRD5A2 rs523349) were associated with differences in body composition at baseline on ADT alone (prior to receipt of AAPA). Elevated subcutaneous adipose tissue index (SATi, p = 0.02), visceral adipose tissue index (VATi, p = 0.03), and BMI (p = 0.04) were associated with satisfactory response to AAPA. Leptin had positive correlation with VATi (r = 0.47) and SATi (r = 0.48). CONCLUSION: Inherited polymorphisms in androgen synthesis correlated with differences in body composition after exposure to ADT and warrant further investigation as candidate markers for body composition toxicity. Elevated subcutaneous and visceral adiposity were associated with improved response to ASI.
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Salvage therapy with high-dose chemotherapy (HDCT) and bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) has curative potential in patients with recurrent germ cell tumor. However, patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCTs) have had poor results with any form of salvage chemotherapy including HDCT. We switched from BMT to PBSCT in 1996. One hundred sixteen of 184 patients (63%) with recurrent or refractory germ cell tumors treated from 1996 to 2004 were alive and continuously disease-free. PMNSGCTs were excluded from that study because of poor results in the patient population with HDCT and BMTs. In 2006, we resumed treating patients with recurrent PMNSGCT with 2 consecutive courses of HDCT consisting of carboplatin 700 mg/m(2) × 3 plus etoposide 750 mg/m(2) × 3 and each followed by an infusion of autologous peripheral-blood hematopoietic stem cells with a second course 3 to 4 weeks later. Twelve patients were treated: 11 as initial salvage chemotherapy and 1 as fourth-line therapy. Eight of the 12 patients had major thoracic resections at the time of the relapse after initial chemotherapy. Three of the 12 patients achieved complete remission (CR; 10, 15, and 50 months' duration). One patient remains continuously with no evidence of disease (NED) at 50 months. An additional patient is currently NED at 52 months with HDCT and subsequent surgery. Median survival for the 12 patients was 11 months (range, 4-52 months). Results with tandem transplant for recurrent PMNSGCT remain poor compared to primary testis cancer, but durable CR and probable cure can be achieved in a small subset of patients with PMNSGCT. In our opinion, salvage surgical resection if anatomically feasible is the preferred option for patients with PMNSGT progressing after initial chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Mediastino/mortalidade , Neoplasias do Mediastino/terapia , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/terapia , Terapia de Salvação , Adolescente , Adulto , Antineoplásicos Fitogênicos/administração & dosagem , Transplante de Medula Óssea , Carboplatina/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Transplante de Células-Tronco de Sangue Periférico , Estudos Retrospectivos , Taxa de Sobrevida , Transplante AutólogoRESUMO
We investigated the prevalence of behavioural change taxonomies in systematic reviews and meta-analyses related to obesity management. In addition, we analysed the funding sources, author conflicts of interest statements, risk of bias, and favorability of the results in such studies to determine if there was a relationship between methodological quality and taxonomy use. We searched several databases including MEDLINE, Epistemonikos, Cochrane EDSR, Pubmed and Embase for systematic reviews and meta-analyses regarding the behavioural treatment of obesity. Screening and data extraction was performed in a masked, duplicate fashion. We performed statistical analyses to determine any significant association between use of taxonomy and study characteristics. Fifteen (of 186; 8.06%) systematic reviews used a taxonomy-nine used the BCTTv1, three used OXFAB, two used the CALO-RE and one used "Taxonomy of choice architecture techniques." Most interventions that referenced a taxonomy were self-mediated (6/60, 10%). Behavioural change taxonomies were mentioned in 10 (of 87, 11.49%) studies with a public funding source. Of the studies with favourable results, 14 studies (of 181, 7.73%) referred to a taxonomy. We found no statistically significant relationships between use of taxonomy and study characteristics. We found that systematic reviews regarding the management of obesity rarely mention a behavioural change taxonomy. Given the global burden of obesity, it is crucial that behavioural change techniques are reproducible and translatable. We recommend that researchers look further into how taxonomies affect the quality and reproducibility of behavioural interventions in an effort to improve patient outcomes.
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Manejo da Obesidade , Humanos , MEDLINE , Obesidade/terapia , Reprodutibilidade dos Testes , Revisões Sistemáticas como Assunto , Metanálise como AssuntoRESUMO
PURPOSE: Immune checkpoint inhibitors (ICIs) are frequently associated with adverse events, often affecting the gastrointestinal tract. We conducted this study to determine the characteristics and outcomes of cancer patients with pre-existing microscopic colitis (MC) who underwent ICI treatment. METHODS: In this retrospective study, we identified 10 patients with pre-existing MC who received ICIs at our center 01/2010-06/2020. Clinical characteristics and disease outcomes were recorded. RESULTS: Of 124 screened patients with MC before ICI exposure, 10 had sufficient data to be included in the study. Melanoma (40%) and lung cancer (30%) were the most prevalent cancer types, with 70% of stage IV cancer. Patients received either anti-programmed death 1 regimen (8, 80%) or anti-programmed death ligand 1 agent (2, 20%). Six patients (60%) had collagenous colitis, and 4 (40%) had lymphocytic colitis. The median time from MC diagnosis to ICI initiation was 4 years, with 1 patient on budesonide within 2 months of ICI initiation. Eight patients (80%) developed colitis exacerbations after ICI and required selective immunosuppression. One patient received a compassionate-use fecal transplantation. The median time from ICI to colitis exacerbation was 14 days, with 40% and 50% of patients experiencing grade 3 diarrhea and grade 2 colitis, respectively, leading to hospitalization in 3 patients. Six patients received steroids and vedolizumab with no colitis recurrence. Of 8 patients who had colitis exacerbation, 6 resumed ICI therapy afterward; with 5 receiving concomitant vedolizumab for secondary prophylaxis. CONCLUSION: Our findings suggest that ICI exposure increases the risk of exacerbation of underlying colitis necessitating and responding to potent immunosuppression therapy.
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Antineoplásicos Imunológicos , Colite Microscópica , Colite , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Receptor de Morte Celular Programada 1 , Estudos Retrospectivos , Antineoplásicos Imunológicos/efeitos adversos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Colite Microscópica/induzido quimicamente , Colite Microscópica/tratamento farmacológicoRESUMO
Given the central role of the androgen receptor (AR) in prostate cancer cell biology, AR-targeted therapies have been the backbone of prostate cancer treatment for over 50 years. New data indicate that AR is expressed in additional cell types within the tumor microenvironment. Moreover, targeting AR for the treatment of prostate cancer has established side effects such as bone complications and an increased risk of developing cardiometabolic disease, indicating broader roles for AR. With the advent of novel technologies, such as single-cell approaches and advances in preclinical modeling, AR has been identified to have clinically significant functions in other cell types. In this mini-review, we describe new cancer cell-extrinsic roles for AR within the tumor microenvironment as well as systemic effects that collectively impact prostate cancer progression and patient outcomes.
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Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Humanos , Masculino , Antagonistas de Receptores de Andrógenos , Osso e Ossos/metabolismo , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Receptores Androgênicos/metabolismo , Microambiente TumoralRESUMO
OBJECTIVES: Immune checkpoint inhibitors (ICI) can cause immune-related adverse events (irAEs) such as colitis. irAEs can be managed by selective immunosuppressive therapy (SIT) agents such as infliximab and vedolizumab. We aimed to elucidate the incidence of subsequent new irAEs after exposure to SIT by describing patients' clinical course. METHODS: We conducted a retrospective chart review of adult patients at a tertiary cancer center diagnosed with ICI-mediated colitis (IMC) treated with SIT from February 2013 through October 2021. Patients' clinical courses, treatments, and outcomes of new irAEs after SIT were collected and analyzed. RESULTS: The study included 156 patients. Most were male (67.3%), 44.8% had melanoma, and 43.5% received anti-PD1/L1 ICIs. For IMC treatment, 51.9% received infliximab and 37.8% received vedolizumab. Twenty-six patients (16.6%) resumed ICI treatment after their colitis event. Twenty-five patients (16%) developed a new irAE after receiving SIT. The most common new irAE involved skin (44%), and most (60%) were treated with steroids. Higher diarrhea grade and ≥2 doses of SIT were associated with lower incidence of post-SIT irAEs ( P =0.038, P =0.050). However, the type of SIT or individual dosage of infliximab did not affect the occurrence of subsequent irAEs. CONCLUSIONS: New irAEs usually occur more than 6 months after SIT completion for initial colitis event. Severe diarrhea grade and higher number of SIT infusions appeared to have protective effect to lower the occurrence of new irAEs. Otherwise, the type of SIT or individual dosage of infliximab did not affect the occurrence of subsequent irAEs.
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Antineoplásicos Imunológicos , Colite , Melanoma , Adulto , Humanos , Masculino , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Infliximab/efeitos adversos , Estudos Retrospectivos , Antineoplásicos Imunológicos/uso terapêutico , Melanoma/tratamento farmacológico , Colite/induzido quimicamente , Terapia de Imunossupressão/efeitos adversos , Diarreia/induzido quimicamenteRESUMO
Aggressive-variant prostate cancers (AVPCs) are a subset of metastatic castrate-resistant prostate cancers (mCRPCs) characterized by defects in ≥ two of three of TP53, RB1, and PTEN (AVPCm), a profile linked to lineage plasticity, androgen indifference, and platinum sensitivity. Men with mCRPC undergoing biopsies for progression were assessed for AVPCm using immunohistochemistry (IHC), next-generation sequencing (NGS) of solid tumor DNA (stDNA), and NGS of circulating tumor DNA (ctDNA) assays in CLIA-certified labs. Biopsy characteristics, turnaround times, inter-reader concordance, and inter-assay concordance were assessed. AVPCm was detected in 13 (27%) patients via IHC, two (6%) based on stDNA, and seven (39%) based on ctDNA. The concordance of the IHC reads between pathologists was variable. IHC had a higher detection rate of AVPCm+ tumors with the shortest turnaround times. stDNA had challenges with copy number loss detection, limiting its detection rate. ctDNA detected the greatest proportion of AVPCm+ tumors but had a low tumor content in two thirds of patients. These data show the operational characteristics of AVPCm detection using various assays, and inform trial design using AVPCm as a criterion for patient selection or stratification.
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BACKGROUND: The prostate tumor microenvironment (TME) is immunosuppressive, with few effector T cells and enrichment of inhibitory immune populations, leading to limited responses to treatments such as immune checkpoint therapies (ICTs). The immune composition of the prostate TME differs across soft tissue and bone, the most common site of treatment-refractory metastasis. Understanding immunosuppressive mechanisms specific to prostate TMEs will enable rational immunotherapy strategies to generate effective antitumor immune responses. Daratumumab (anti-CD38 antibody) and edicotinib (colony-stimulating factor-1 receptor (CSF-1R) inhibitor) may alter the balance within the prostate TME to promote antitumor immune responses. HYPOTHESIS: Daratumumab or edicotinib will be safe and will alter the immune TME, leading to antitumor responses in localized prostate cancer. PATIENTS AND METHODS: In this presurgical study, patients with localized prostate cancer received 4 weekly doses of daratumumab or 4 weeks of daily edicotinib prior to radical prostatectomy (RP). Treated and untreated control (Gleason score ≥8 in prostate biopsy) prostatectomy specimens and patient-matched pre- and post-treatment peripheral blood mononuclear cells (PBMCs) and bone marrow samples were evaluated. The primary endpoint was incidence of adverse events (AEs). The secondary endpoint was pathologic complete remission (pCR) rate. RESULTS: Twenty-five patients were treated (daratumumab, n=15; edicotinib, n=10). All patients underwent RP without delays. Grade 3 treatment-related AEs with daratumumab occurred in 3 patients (12%), and no ≥grade 3 treatment-related AEs occurred with edicotinib. No changes in serum prostate-specific antigen (PSA) levels or pCRs were observed. Daratumumab led to a decreased frequency of CD38+ T cells, natural killer cells, and myeloid cells in prostate tumors, bone marrow, and PBMCs. There were no consistent changes in CSF-1R+ immune cells in prostate, bone marrow, or PBMCs with edicotinib. Neither treatment induced T cell infiltration into the prostate TME. CONCLUSIONS: Daratumumab and edicotinib treatment was safe and well-tolerated in patients with localized prostate cancer but did not induce pCRs. Decreases in CD38+ immune cells were observed in prostate tumors, bone marrow, and PBMCs with daratumumab, but changes in CSF-1R+ immune cells were not consistently observed with edicotinib. Neither myeloid-targeted agent alone was sufficient to generate antitumor responses in prostate cancer; thus, combinations with agents to induce T cell infiltration (eg, ICTs) will be needed to overcome the immunosuppressive prostate TME.
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Antineoplásicos , Neoplasias da Próstata , Masculino , Humanos , Leucócitos Mononucleares/patologia , Antineoplásicos/uso terapêutico , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Imunossupressores , Microambiente TumoralRESUMO
Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03). Conclusions: Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality. Funding: National Cancer Institute and National Institutes of Health.
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COVID-19 , Linfopenia , Neoplasias , Humanos , COVID-19/complicações , COVID-19/terapia , Estudos Retrospectivos , SARS-CoV-2 , Sobrevivência , Fatores de Risco , Neoplasias/complicações , Neoplasias/epidemiologia , OxigênioRESUMO
The addition of atezolizumab (anti-PD-L1) to enzalutamide (androgen receptor antagonist) did not prolong survival in metastatic prostate cancer.1 Efficacy with immunotherapies in prostate cancer will require additional studies to elucidate and target mechanisms of resistance within the prostate tumor microenvironment.