RESUMEN
BACKGROUND: Solid cancer is an independent prognostic factor for poor outcome with COVID-19. As guidelines for patient management in that setting depend on retrospective efforts, we here present the first analyses of a nationwide database of patients with cancer hospitalized with COVID-19 in Belgium, with a focus on changes in anticancer treatment plans at the time of SARS-CoV-2 infection. METHODS: Nineteen Belgian hospitals identified all patients with a history of solid cancer hospitalized with COVID-19 between March 2020 and February 2021. Demographic, cancer-specific and COVID-specific data were pseudonymously entered into a central Belgian Society of Medical Oncology (BSMO)-COVID database. The association between survival and primary cancer type was analyzed through multivariate multinomial logistic regression. Group comparisons for categorical variables were carried out through a Chi-square test. RESULTS: A total of 928 patients were registered in the database; most of them were aged ≥70 years (61.0%) and with poor performance scores [57.2% Eastern Cooperative Oncology Group (ECOG) ≥2]. Thirty-day COVID-related mortality was 19.8%. In multivariate analysis, a trend was seen for higher mortality in patients with lung cancer (27.6% versus 20.8%, P = 0.062) and lower mortality for patients with breast cancer (13.0% versus 23.3%, P = 0.052) compared with other tumour types. Non-curative treatment was associated with higher 30-day COVID-related mortality rates compared with curative or no active treatment (25.8% versus 14.3% versus 21.9%, respectively, P < 0.001). In 33% of patients under active treatment, the therapeutic plan was changed due to COVID-19 diagnosis, most frequently involving delays/interruptions in systemic treatments (18.6%). Thirty-day COVID-related mortality was not significantly different between patients with and without treatment modifications (21.4% versus 20.5%). CONCLUSION: Interruption in anticancer treatments at the time of SARS-CoV-2 infection was not associated with a reduction in COVID-related mortality in our cohort of patients with solid cancer, highlighting that treatment continuation should be strived for, especially in the curative setting.
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COVID-19 , Neoplasias Pulmonares , Humanos , Bélgica/epidemiología , SARS-CoV-2 , Estudios Retrospectivos , Prueba de COVID-19 , Neoplasias Pulmonares/tratamiento farmacológico , Oncología Médica , Sistema de RegistrosRESUMEN
BACKGROUND: The viral pandemic coronavirus disease 2019 (COVID-19) has disrupted cancer patient management around the world. Most reported data relate to incidence, risk factors, and outcome of severe COVID-19. The safety of systemic anti-cancer therapy in oncology patients with non-severe COVID-19 is an important matter in daily practice. METHODS: ONCOSARS-1 was a single-center, academic observational study. Adult patients with solid tumors treated in the oncology day unit with systemic anti-cancer therapy during the initial phase of the COVID-19 pandemic in Belgium were prospectively included. All patients (n = 363) underwent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) serological testing after the first peak of the pandemic in Belgium. Additionally, 141 of these patients also had a SARS-CoV-2 RT-PCR test during the pandemic. The main objective was to retrospectively determine the safety of systemic cancer treatment, measured by the rate of adverse events according to the Common Terminology Criteria for Adverse Events, in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative patients. RESULTS: Twenty-two (6%) of the 363 eligible patients were positive for SARS-CoV-2 by RT-PCR and/or serology. Of these, three required transient oxygen supplementation, but none required admission to the intensive care unit. Hematotoxicity was the only adverse event more frequently observed in SARS-CoV-2 -positive patients than in SARS-CoV-2-negative patients: 73% vs 35% (P < 0.001). This association remained significant (odds ratio (OR) 4.1, P = 0.009) even after adjusting for performance status and type of systemic treatment. Hematological adverse events led to more treatment delays for the SARS-CoV-2-positive group: 55% vs 20% (P < 0.001). Median duration of treatment interruption was similar between the two groups: 14 and 11 days, respectively. Febrile neutropenia, infections unrelated to COVID-19, and bleeding events occurred at a low rate in the SARS-CoV-2-positive patients. CONCLUSION: Systemic anti-cancer therapy appeared safe in ambulatory oncology patients treated during the COVID-19 pandemic. There were, however, more treatment delays in the SARS-CoV-2-positive population, mainly due to a higher rate of hematological adverse events.
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COVID-19/diagnóstico , COVID-19/epidemiología , Neoplasias/terapia , Anciano , Atención Ambulatoria/estadística & datos numéricos , Bélgica/epidemiología , COVID-19/complicaciones , Instituciones Oncológicas , Estudios de Cohortes , Femenino , Personal de Salud/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Factores de Riesgo , SARS-CoV-2RESUMEN
Background: Immune checkpoint inhibitors (icis) are increasingly being used in clinical practice, improving outcomes for cancer patients. Preclinical models showed significant interaction between the gut microbiome (gm) and response to icis. However, that interaction remains unclear in clinical practice. Methods: We performed a systematic review in medline to determineâ whether antibiotics affect ici efficacy,â whether baseline gm composition and ici efficacy show any correlations,â whether baseline gm composition and emergence of immune-related adverse events (iraes) show any correlations, andâ whether gm manipulation can alleviate the iraes.Included publications had to be written in English or French and had to describe a quantifiable link between gm composition or its modification and the response to icis or the occurrence of iraes, or both. Results: Of 1451 articles published before December 2018, 13 publications met the inclusion criteria. Five full-text articles and two abstracts highlighted a negative effect of antibiotics on ici efficacy. The composition of the gm was associated with ici efficacy in five full-text articles and one abstract, and with iraes in two full-text articles. In 2 cases, fecal microbiota transplantation was reported to reduce immune colitis. Conclusions: If possible, antibiotics should be avoided before ici treatment because of their negative effect on ici anticancer efficacy. No specific commensal bacterium was associated with ici efficacy, but an intact gm with high bacterial diversity and a good ratio of "responder-associated" bacteria to "non-responder-associated" bacteria seem to be correlated with better patient outcomes. Fecal microbiota transplantation is a promising technique for reducing ici-associated colitis.
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Antineoplásicos Inmunológicos/uso terapéutico , Microbioma Gastrointestinal , Neoplasias/tratamiento farmacológico , Neoplasias/microbiología , Antibacterianos/uso terapéutico , Humanos , Resultado del TratamientoRESUMEN
Palmar fasciitis and polyarthritis syndrome (PFPAS) is an uncommon disorder characterized by diffuse inflammation of the palmar fascia, tendon sheaths, and joints of the fingers and wrists, which rapidly progresses to flexion contracture of the hands. This paraneoplastic syndrome, originally linked to ovarian carcinoma, has also been associated with multiple different malignancies. As PFPAS usually precedes the detection of cancer, its symptoms should raise the suspicion of an underlying malignancy and should be thoroughly investigated.
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Artritis/etiología , Carcinoma/complicaciones , Fascitis/etiología , Dermatosis de la Mano/etiología , Neoplasias Ováricas/complicaciones , Síndromes Paraneoplásicos/etiología , Anciano , Femenino , HumanosRESUMEN
BACKGROUND: Hypoxia can activate autophagy, a self-digest adaptive process that maintains cell turnover. Mammalian target of rapamycin (mTOR) inhibitors are used to treat cancer but also stimulate autophagy. METHODS: Human mammary cancer cells and derived xenografts were used to examine whether hypoxia could exacerbate autophagy-mediated resistance to the mTOR inhibitor rapamycin. RESULTS: Rapamycin exerted potent antitumour effects in MCF-7 and MDA-MB-231 mammary tumours through a marked inhibition of angiogenesis, but the autophagy inhibitor chloroquine (CQ) failed to further sensitise tumours to mTOR inhibition. Rapamycin treatment actually led to tumour reoxygenation, thereby preventing the development of autophagy. Chloroquine alone, however, blocked the growth of MCF-7 tumours and in vitro blunted the hypoxia-induced component of autophagy in these cells. Finally, when initiating CQ treatment in large, hypoxic tumours, a robust antitumour effect could be observed, which also further increased the antiproliferative effects of rapamycin. CONCLUSION: The mTOR inhibitor rapamycin significantly contributes to tumour growth inhibition and normalisation of the tumour vasculature through potent antiangiogenic effects. The resulting reduction in hypoxia accounts for a lack of sensitisation by the autophagy inhibitor CQ, except if the tumours are already at an advanced stage, and thus largely hypoxic at the initiation of the combination of rapamycin and CQ treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Autofagia/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Cloroquina/administración & dosificación , Sirolimus/administración & dosificación , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Animales , Neoplasias de la Mama/metabolismo , Hipoxia de la Célula/fisiología , Femenino , Humanos , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/metabolismo , Neoplasias Mamarias Experimentales/patología , Ratones Desnudos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Preclinical studies have shown that PTEN loss enhances sensitivity to mammalian target of Rapamycin (mTOR) inhibitors because of facilitated PI3K (phosphatidylinositol-3 kinase)/Akt activation and consecutive stimulation of the mTOR pathway. In patients with advanced transitional cell carcinoma (TCC) treated with the mTOR inhibitor everolimus, PTEN loss was, however, associated with resistance to treatment. METHODS: Transitional cell carcinoma specimens, human bladder cancer cells and derived mouse xenografts were used to evaluate how the PTEN status influences the activity of mTOR inhibitors. RESULTS: Transitional cell carcinoma patients with a shorter progression-free survival under everolimus exhibited PTEN deficiency and increased Akt activation. Moreover, PTEN-deficient bladder cancer cells were less sensitive to rapamycin than cells expressing wild-type PTEN, and rapamycin strikingly induced Akt activation in the absence of functional PTEN. Inhibition of Akt activation by the PI3K inhibitor wortmannin interrupted this rapamycin-induced feedback loop, thereby enhancing the antiproliferative effects of the mTOR inhibitor both in vitro and in vivo. CONCLUSION: Facilitation of Akt activation upon PTEN loss can have a more prominent role in driving the feedback loop in response to mTOR inhibition than in promoting the mTOR pathway. These data support the use of both PI3K and mTOR inhibitors to treat urothelial carcinoma, in particular in the absence of functional PTEN.
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Carcinoma de Células Transicionales/tratamiento farmacológico , Fosfohidrolasa PTEN/deficiencia , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Androstadienos/farmacología , Animales , Antineoplásicos/farmacología , Carcinoma de Células Transicionales/enzimología , Carcinoma de Células Transicionales/patología , Línea Celular Tumoral , Ensayos Clínicos Fase II como Asunto , Supervivencia sin Enfermedad , Interacciones Farmacológicas , Activación Enzimática/efectos de los fármacos , Everolimus , Femenino , Humanos , Ratones , Ratones Desnudos , Fosforilación , Sirolimus/administración & dosificación , Sirolimus/análogos & derivados , Neoplasias de la Vejiga Urinaria/enzimología , Neoplasias de la Vejiga Urinaria/patología , Wortmanina , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: This phase II study assessed the safety and efficacy of everolimus, an oral mammalian target of rapamycin inhibitor in advanced transitional carcinoma cell (TCC) after failure of platinum-based therapy. PATIENTS AND METHODS: Thirty-seven patients with advanced TCC received everolimus 10 mg/day until progressive disease (PD) or unacceptable toxicity. The primary end point was the disease control rate (DCR), defined as either stable disease (SD), partial response (PR), or complete response at 8 weeks. Angiogenesis-related proteins were detected in plasma and changes during everolimus treatment were analyzed. PTEN expression and PIK3CA mutations were correlated to disease control. RESULTS: Two confirmed PR and eight SD were observed, resulting in a DCR of 27% at 8 weeks. Everolimus was well tolerated. Compared with patients with noncontrolled disease, we observed in patients with controlled disease a significant higher baseline level of angiopoietin-1 and a significant early plasma decrease in angiopoietin-1, endoglin, and platelet-derived growth factor-AB. PTEN loss was observed only in patients with PD. CONCLUSIONS: Everolimus showed clinical activity in advanced TCC. The profile of the plasma angiogenesis-related proteins suggested a role of the everolimus antiangiogenic properties in disease control. PTEN loss might be associated with everolimus resistance.
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Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Transicionales/tratamiento farmacológico , Sirolimus/análogos & derivados , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos/efectos adversos , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/patología , Everolimus , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Sirolimus/efectos adversos , Sirolimus/uso terapéutico , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Nearly half of patients with colorectal cancer will have metastases in the course of their disease and the liver appears to be the most common location for metastases. For patients with confined hepatic colorectal metastases, complete surgical resection is the only chance for cure, with a 5-year postoperative survival rate between 35% and 50%. Over the past 5 years, combinations of chemotherapy with targeted therapies have succeeded in inducing tumoral response and have made curative surgery of initially unresectable liver metastases possible. However despite optimal preoperative treatment, disease in the majority of patients remains unresectable. For patients with liver-limited or liver-dominant metastatic colorectal cancer (mCRC), the current challenges are to explore different locoregional treatments to improve local control, overall survival (OS), and curative resection. In this way, liver-directed therapy, which is defined by injection, infusion, or embolization of chemotherapy or loaded radionuclide (with radioactive yttrium-90) microspheres into the arterial liver vasculature, has been an appealing investigational method for patients with liver-confined mCRC, in whom it has yielded reproducibly higher response rates (RRs) than conventional intravenous therapy. In this article, we propose to review, compare, and discuss the clinical benefit, the current indications, and the optimal use of liver-directed therapies for patients with liver-dominant mCRC.
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Antineoplásicos/uso terapéutico , Braquiterapia , Neoplasias Colorrectales/patología , Embolización Terapéutica , Neoplasias Hepáticas/terapia , Radioisótopos de Itrio/uso terapéutico , Arteria Hepática , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/secundarioRESUMEN
We report the case of a woman with a metastatic breast cancer, who started a third-line treatment with dasatinib, a new oral tyrosine kinase inhibitor, and who developed, one week later, a progressive breathless sensation. Workup demonstrated pleuropericardial effusion that turned out to be a side effect of this new investigational drug. Although this dasatinib-induced side effect is well known, this case clearly illustrates the importance of an accurate diagnosis and adequate treatment of complications of new agents which are easy to use since most of them are orally taken, and the difficulty to clearly separate drug origin and cancer morbidities. The patient recovered completely one month after discontinuation of dasatinib. In this report, we will review the differential diagnosis and management of pleuropericardial effusion.