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INTRODUCTION: Colorectal cancer is one of the most common malignant tumors and has a relatively poor prognosis. Lymph node involvement is considered the most important prognostic factor. MATERIALS AND METHODS: During a retrospective cohort study, 132 patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy followed by surgery for resectable rectal cancer from 2010 to 2015 in Sina hospital were reviewed. RESULTS: Multivariable analysis was performed and shown the clinical stage was not a representative factor for disease-free survival (P = 0.187), but Dworak Tumor Regression Grading were significantly associated with higher disease-free survival (P = 0.000) in stage II and stage III. The total number of retrieved lymph nodes and involved lymph nodes in the same clinical stage were statistically associated with higher mean disease-free survival in patients (P = 0.000 in both conditions). CONCLUSION: In the same clinical stage, increasing the Dworak Tumor Regression Grading reduced the risk of rectal cancer recurrence. Increasing total number of retrieved lymph nodes and involved lymph nodes, 2.14 times and 3.87 times increased the risk of recurrence, respectively.
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Adenocarcinoma/patología , Ganglios Linfáticos/patología , Terapia Neoadyuvante/normas , Recurrencia Local de Neoplasia , Neoplasias del Recto/patología , Adenocarcinoma/clasificación , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Quimioterapia/normas , Femenino , Humanos , Ganglios Linfáticos/efectos de los fármacos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Radioterapia/normas , Neoplasias del Recto/clasificación , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/terapia , Recto/patología , Estudios RetrospectivosRESUMEN
Among the different chemotherapies available, genotoxic drugs are widely used. In response to these drugs, particularly doxorubicin, tumor cells can enter into senescence. Chemotherapyinduced senescence (CIS) is a complex response. Long described as a definitive arrest of cell proliferation, the present authors and various groups have shown that this state may not be complete and could allow certain cells to reproliferate. The mechanism could be due to the activation of new signaling pathways. In the laboratory, the proteins involved in these pathways and triggering cell proliferation were studied. The present study determined a new role for anterior gradient protein 2 (AGR2) in vivo in patients and in vitro in a senescence escape model. AGR2's implication in breast cancer patients and proliferation of senescent cells was assessed based on a SWATHMS proteomic study of patients' samples and RNA interference technology on cell lines. First, AGR2 was identified and it was found that its concentration is higher in the serum of patients with breast cancer and that this high concentration is associated with metastasis occurrence. An inverse correlation between intratumoral AGR2 expression and the senescence marker p16 was also observed. This observation led to the study of the role of AGR2 in the CIS escape model. In this model, it was found that AGR2 is overexpressed in cells during senescence escape and that its loss considerably reduces this phenomenon. Furthermore, it was shown that the extracellular form of AGR2 stimulated the reproliferation of senescent cells. The power of proteomic analysis based on the SWATHMS approach allowed the present study to highlight the mammalian target of rapamycin (mTOR)/AKT signaling pathway in the senescence escape mechanism mediated by AGR2. Analysis of the two signaling pathways revealed that AGR2 modulated RICTOR and AKT phosphorylation. All these results showed that AGR2 expression in sera and tumors of breast cancer patients is a marker of tumor progression and metastasis occurrence. They also showed that its overexpression regulates CIS escape via activation of the mTOR/AKT signaling pathway.
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Neoplasias de la Mama/tratamiento farmacológico , Senescencia Celular/genética , Mucoproteínas/análisis , Proteínas Oncogénicas/análisis , Biomarcadores/análisis , Biomarcadores/sangre , Neoplasias de la Mama/genética , Línea Celular Tumoral/citología , Línea Celular Tumoral/metabolismo , Senescencia Celular/fisiología , Quimioterapia/normas , Quimioterapia/estadística & datos numéricos , Femenino , Humanos , Mucoproteínas/sangre , Proteínas Oncogénicas/sangreRESUMEN
BACKGROUND: Non-small-cell lung cancer (NSCLC) is a major health burden in many countries. This review aimed to evaluate the efficacy of traditional herbal medicine (THM) combined with first-line platinum-based chemotherapy (PBCT) for the treatment of advanced NSCLC. METHODS: From inception to April 2021, relevant studies were retrieved from 9 electronic databases. Randomized controlled trials (RCTs) comparing survival outcomes of THMâ+âPBCT treatment with PBCT treatment in patients with advanced NSCLC were reviewed. The risk of bias was evaluated using the Cochrane Risk of Bias Tool. Overall survival, 1-year survival, progression-free survival or time to progression, tumor response rate, and adverse effects were analyzed. RESULTS: Sixteen RCTs comprising 1445 patients were included. The meta-analysis indicated that THMâ+âPBCT treatment, compared to PBCT alone, could improve overall survival (median survival ratioâ=â1.24, 95% confidence intervals [CI] [1.11, 1.39], Pâ<â.001), progression-free survival/time to progression (median survival ratioâ=â1.22, 95% CI [1.09, 1.37], Pâ<â.001), and the 1-year survival rate (risk ratio [RR]â=â1.56, 95% CI [1.31, 1.86], Pâ<â.001). THMâ+âPBCT also led to a higher tumor response rate (RRâ=â1.39, 95% CI [1.22, 1.59], Pâ<â.001) and lower incidence of thrombocytopenia (RRâ=â0.72, 95% CI [0.56, 0.92], Pâ=â.009) and nausea/vomiting (RRâ=â0.35, 95% CI [0.21, 0.57], Pâ<â.001), while there was no significant effect observed on leukopenia (RRâ=â0.68, 95% CI [0.34, 1.36], Pâ=â.27). CONCLUSION: THM, when used in combination with PBCT, might increase survival and the tumor response rate while decreasing the side effects caused by chemotherapy in patients with advanced NSCLC. However, considering the limited methodological qualities of the included trials, more rigorous RCTs are needed.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Quimioterapia/normas , Medicina Tradicional/normas , Platino (Metal)/farmacología , Quimioterapia/métodos , Humanos , Medicina Tradicional/métodos , Platino (Metal)/uso terapéutico , Supervivencia sin Progresión , Análisis de SupervivenciaRESUMEN
OBJECTIVE: When treated for childhood cancers, at least 50% of children exposed to platinum agents have permanent hearing loss. We determined the relative risk of childhood hearing loss after in utero exposure to platinum chemotherapy in our registry cohort. METHOD: After exposure to platinum chemotherapy in utero, all children undergo routine newborn hearing screening. This consists of Otoacoustic Emissions. Children who failed this screen were evaluated by audiologists. For those children with hearing loss by Automated Auditory Brainstem Response, prenatal and postnatal treatment details were compared to platinum exposed children without hearing loss. RESULTS: Three hundred and seven children were exposed to chemotherapy in utero. Four children were diagnosed with hearing loss, all exposed to platinum agents. Chemotherapy exposures included: Cisplatin/Paclitaxel (2), Etoposide/Cisplatin/Bleomycin (1), Carboplatin/Paclitaxel (1) to treat ovarian (2), or cervical cancer (2). Of the 39 platinum exposed without hearing loss: 11 children were exposed to oxaliplatin, 16 were exposed to cisplatin and 12 to carboplatin in utero. Two hundred and sixty four women received non-platinum based chemotherapy for various cancers during pregnancy. Among these, there were no cases of hearing loss. There was a significant difference in hearing loss based on exposure to platinum agents in utero compared to non-platinum-containing chemotherapy regimens, 4/43 versus 0/264, p = 0.0003. There were no statistical differences in prenatal and postnatal treatment details, including: gestational age at diagnosis, at first chemotherapy treatment, at first platinum treatment, at delivery (<32 weeks, <35 weeks, <37 weeks), gender, birthweight, birthweight percentile, rates of intrauterine growth restriction, neonatal complications or use of postnatal antibiotics between the platinum exposed children with and without hearing loss. CONCLUSION: The only children in the registry exposed to chemotherapy who were diagnosed with hearing loss had been exposed to cisplatin or carboplatin in utero. No hearing loss occurred in children exposed to oxaliplatin, or non-platinum agents. Due to a concern for cisplatin ototoxicity, carboplatin is the preferred platinum agent for use in pregnancy when equivalent maternal survival can be expected for the particular cancer type. For newborns exposed to platinum agents in utero, newborn screening with an auditory emissions test at birth (OES) may not detect sensorineural hearing loss and auditory brainstem response testing is recommended, regardless of the newborn screening result.
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Exposición a Riesgos Ambientales/efectos adversos , Pérdida Auditiva/etiología , Platino (Metal)/efectos adversos , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Niño , Estudios de Cohortes , Quimioterapia/métodos , Quimioterapia/normas , Quimioterapia/estadística & datos numéricos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Femenino , Pérdida Auditiva/epidemiología , Humanos , Incidencia , Lactante , Recién Nacido , Platino (Metal)/administración & dosificación , EmbarazoRESUMEN
ABSTRACT: Currently, the impact of chemotherapy (CT) on survival outcomes in elderly patients with nasopharyngeal carcinoma (NPC) receiving radiation therapy (RT) remains controversial. This retrospective study aims to investigate survival outcomes in a cohort of elderly NPC patients receiving RT alone or together with CT.Clinical data on 529 NPC patients aged 65âyears and older extracted from the Surveillance, Epidemiology, and End Results registry (2004-2015) was collected and retrospectively reviewed. In this cohort, 74 patients were treated with RT alone and 455 individuals received RT and CT. We used propensity score matching with a 1:3 ratio to identify correlations between patients based on 6 different variables. Kaplan-Meier analysis was used to evaluate overall (OS) and cancer-specific survival (CSS). The differences in OS and CSS between the 2 treatment groups were compared using the Log-rank test and Cox proportional hazards models.The estimated 5-year OS and CSS rates for all patients were 49.5% and 59.3%, respectively. The combination of RT and CT provided longer OS than RT alone (53.7% vs 36.9%, Pâ=â.002), while no significant difference was observed in CSS (61.8% vs 51.7%, Pâ=â.074) between the 2 groups. Moreover, multivariate analysis demonstrated that the combination of CT and RT correlated favorably with OS and CSS. Subgroup analyses showed that the combination of RT and CT correlated better with both OS and CSS in patients with stage T3 or N2 or stage III.Among NPC patients aged 65âyears and older, treatment with RT and CT provided longer OS than RT alone. Furthermore, the combination of RT and CT showed a better correlation with OS and CSS in NPC patients with stage T3 or N2 or stage III.
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Quimioterapia/normas , Neoplasias Nasofaríngeas/terapia , Radioterapia/normas , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Quimioterapia/métodos , Quimioterapia/estadística & datos numéricos , Femenino , Geriatría/métodos , Humanos , Masculino , Neoplasias Nasofaríngeas/fisiopatología , Modelos de Riesgos Proporcionales , Radioterapia/métodos , Radioterapia/estadística & datos numéricos , Estudios Retrospectivos , Programa de VERFRESUMEN
The human body harbors a diverse microbiome that regulates host physiology and disease development. Several studies have also been reported where the human microbiome interferes with the efficacy of chemotherapeutics. Reports have also suggested the use of microbes in specific targeting and drug delivery. This review mainly focuses on the alteration in the efficacy of the drug by human microbiota. We have also discussed how the diversity in microbes can determine the therapeutic outcomes of a particular drug. The pathways involved in the alteration are also focused, with some highlights on microbes being used in cancer therapy.
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Microbiota , Preparaciones Farmacéuticas , Quimioterapia/normas , HumanosRESUMEN
BACKGROUND: Primary or acquired chemoresistance is a key link in the high mortality rate of ovarian cancer. There is no reliable method to predict chemoresistance in ovarian cancer. We hypothesized that specific methylation characteristics could distinguish chemoresistant and chemosensitive ovarian cancer patients. METHODS: In this study, we used 450 K Infinium Methylation BeadChip to detect the different methylation CpGs between ovarian cancer patients. The differential methylation genes were analyzed by GO and KEGG Pathway bioinformatics analysis. The candidate CpGs were confirmed by pyrosequencing. The expression of abnormal methylation gene was identified by QRT-PCR and IHC. ROC analysis confirmed the ability to predict chemotherapy outcomes. Prognosis was evaluated using Kaplan-Meier. RESULTS: In advanced high-grade serous ovarian cancer, 8 CpGs (ITGB6:cg21105318, cg07896068, cg18437633; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934, cg13270625) remained hypermethylated in chemoresistant patients. The sensitivity, specificity and AUC of 8 CpGs (ITGB6:cg21105318, cg07896068, cg18437633; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934, cg13270625) methylation to predict chemotherapy sensitivity were 63.60-97.00%, 46.40-89.30% and 0.774-0.846. PFS of 6 candidate genes (ITGB6:cg21105318, cg07896068; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934) hypermethylation patients was significantly shorter. The expression of NCALD and LAMA3 in chemoresistant patients was lower than that of chemosensitive patients. Spearman analysis showed that NCALD and LAMA3 methylations were negatively correlated with their expression. CONCLUSIONS: As a new biomarker of chemotherapy sensitivity, hypermethylation of NCALD and LAMA3 is associated with poor PFS in advanced high-grade serous ovarian cancer. In the future, further research on NCALD and LAMA3 will be needed to provide guidance for clinical stratification of demethylation therapy.
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Metilación de ADN/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Adulto , China , Metilación de ADN/fisiología , Quimioterapia/métodos , Quimioterapia/normas , Quimioterapia/estadística & datos numéricos , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/fisiopatología , PronósticoRESUMEN
BACKGROUND: Metronomic chemotherapy (MC) strategy has been used in breast cancer for more than a decade since it was first proposed. The purpose of this study is to systematically evaluate its efficacy and safety for breast cancer patients at various stages, as well as to clarify the most effective medication strategy when applying MC and discover its most sensitive subpopulation in breast cancer patients. METHOD: We will systematically retrieve random controlled trials evaluating the efficacy and safety of MC in breast cancer on PubMed, Cochrane Library, Embase, and web of science to perform this network meta-analysis. Markov chain Monte Carlo method based on Bayesian Theory will be used to conduct network meta-analysis and the efficacy and safety will be ranked by combining direct and indirect evidence in mixed treatment comparisons. We will assess the quality of literatures with the Cochrane Risk Bias Assessment Tool and assess the strength of the evidence using the GRADE methodology. Data analysis will be completed with the WinBUGS, R, Stata and RevMan softwares. RESULTS AND CONCLUSION: Through the analysis, we can obtain the ranking of efficacy and safety in different MC strategy, and reveal the specific breast cancer groups that are more sensitive to MC. We access the effectiveness by disease free survival, progress free survival, time to progress, objective response rate, and overall survival, and measure the toxicity by dose-limiting toxicity. The result of our study could provide evidence for clinicians to make a better choice when they consider MC. INPLASY REGISTRATION NUMBER: INPLASY202140142.
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Administración Metronómica , Neoplasias de la Mama/tratamiento farmacológico , Protocolos Clínicos , Quimioterapia/normas , Adulto , Teorema de Bayes , Quimioterapia/métodos , Femenino , Humanos , Metaanálisis como Asunto , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: It is important to assess the burden of chronic urticaria (CU) with real-life studies. The AWARE study was performed in 36 countries over two years in CU patients resistant to H1-antihistamines. OBJECTIVES: To correlate patient-reported outcomes and available therapeutic options in CU patients. MATERIALS & METHODS: The AWARE study was a prospective, non-interventional, international study that included adult patients who have had H1-antihistamine-resistant CU for at least two months. The primary endpoints were the evolution of disease activity (UAS7), urticaria control (UCT), dermatological quality of life (DLQI) and treatment satisfaction (visual analogic scale) during a two-year follow-up. The data from French centres are reported. RESULTS: Ninety-two patients were included (mean age: 47.8 years; women: 70.7%; mean disease duration: 6.5 years; angioedema: 34.1%). The percentage of patients with CU treatment increased from 56.5% at inclusion to 86.0% after two years (for patients with non-sedative H1-antihistamines from 52.2% to 74.4%, and omalizumab from 2.2% to 25.6%). During the follow-up, the percentage of patients with UAS7 score <6 increased from 12.5% to 60.9%, and patients with well-controlled CU (UCT score >12) increased from 11.1% to 62.2%. The negative impact on quality of life (DLQI >10) decreased from 34.1% to 10.5%. The mean score of patient satisfaction for treatment increased from 4.6 to 7.6. CONCLUSION: The management of CU patients resistant to H1-antihistamines was not optimal at inclusion with uncontrolled disease, impaired quality of life and insufficient treatment. After a two-year follow-up, disease symptoms and quality of life improved, but the therapeutic management could be further optimized.
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Antialérgicos/uso terapéutico , Urticaria Crónica/tratamiento farmacológico , Recursos en Salud/estadística & datos numéricos , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Omalizumab/uso terapéutico , Adulto , Costo de Enfermedad , Resistencia a Medicamentos , Quimioterapia/normas , Eficiencia , Femenino , Estudios de Seguimiento , Francia , Humanos , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Satisfacción del Paciente , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Ausencia por Enfermedad/estadística & datos numéricosRESUMEN
We aimed to compare the sperm quality in different cancer types and benign diseases before gonadotoxic treatment, and assess the usage rate of cryopreserved sperm for assisted reproductive treatment (ART). This retrospective study was conducted at two university clinics between January 2008 and July 2018. A total of 545 patients suffering from cancer or benign diseases were included in the study. The pretreatment sperm analyses were based on the World Health Organization (WHO) guidelines. Patients with testicular malignancy (TM) showed a significantly lower sperm count (median [interquartile range]: 18.7 × 106 [5.3 × 106-43.0 × 106] ml-1; P = 0.03) as well as total sperm count (42.4 × 106 [13.3 × 106-108.5 × 106] per ejaculate; P = 0.007) compared to other malignant and benign diseases. In addition, patients with nonseminomatous TM showed the lowest sperm count (14.3 × 106 [6.0 × 106-29.9 × 106] ml-1, vs seminomas: 16.5 × 106 [4.6 × 106-20.3 × 106] ml-1; P = 0.001). With reference to the WHO 2010 guidelines, approximately 48.0% of the patients with TM and 23.0% with hematological malignancies (HM) had oligozoospermia. During the observation period, only 29 patients (5.3%) used their frozen sperms for 48 ART cycles, resulting in 15 clinical pregnancies and 10 live births. The sperm quality varies with the type of underlying disease, with TM and HM patients showing the lowest sperm counts. Due to the observed low usage rate of cryopreserved sperm, further patient interviews and sperm analyses should be included in the routine oncologic protocols to avoid unnecessary storage expenses. However, sperm banking is worth the effort as it provides hope for men who cannot reproduce naturally after gonadotoxic treatment.
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Quimioterapia/normas , Neoplasias/tratamiento farmacológico , Preservación de Semen/estadística & datos numéricos , Adulto , Análisis de Varianza , Quimioterapia/métodos , Quimioterapia/estadística & datos numéricos , Humanos , Masculino , Neoplasias/fisiopatología , Estudios Retrospectivos , Preservación de Semen/métodos , Bancos de Esperma/organización & administración , Bancos de Esperma/estadística & datos numéricos , Resultado del TratamientoRESUMEN
BACKGROUND: In cardiovascular disease, prevention strategies targeting standard modifiable cardiovascular risk factors (SMuRFs; hypertension, diabetes, hypercholesterolaemia, and smoking) are crucial; however, myocardial infarction in the absence of SMuRFs is not infrequent. The outcomes of individuals without SMuRFs are not well known. METHODS: We retrospectively analysed adult patients with first-presentation ST-elevation myocardial infarction (STEMI) using data from the Swedish myocardial infarction registry SWEDEHEART. Clinical characteristics and outcomes of adult patients (age ≥18 years) with and without SMuRFs were examined overall and by sex. Patients with a known history of coronary artery disease were excluded. The primary outcome was all-cause mortality at 30 days after STEMI presentation. Secondary outcomes included cardiovascular mortality, heart failure, and myocardial infarction at30 days. Endpoints were also examined up to discharge, and to the end of a 12-year follow-up. Multivariable logistic regression models were used to compare in-hospital mortality, and Cox-proportional hazard models and Kaplan-Meier analysis for long-term outcomes. FINDINGS: Between Jan 1, 2005, and May 25, 2018, 9228 (14·9%) of 62 048 patients with STEMI had no SMuRFs reaching diagnostic thresholds. Median age was similar between patients with SMuRFs and patients without SMuRFs (68 years [IQR 59-78]) vs 69 years [60-78], p<0·0001). SMuRF-less patients had a similar rate of percutaneous coronary intervention to those with at least one modifiable risk factor, but were significantly less likely to receive statins, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockade (ARB), or ß-blockers at discharge. By 30 days after presentation, all-cause mortality was significantly higher in SMuRF-less patients (hazard ratio 1·47 [95% CI 1·37-1·57], p<0·0001). SMuRF-less women had the highest 30-day mortality (381 [17·6%] of 2164), followed by women with SMuRFs (2032 [11·1%] of 18 220), SMuRF-less men (660 [9·3%] of 7064), and men with SMuRFs (2117 [6·1%] of 34 600). The increased risk of 30-day all-cause mortality in SMuRF-less patients remained significant after adjusting for age, sex, left ventricular ejection fraction, creatinine, and blood pressure, but was attenuated on inclusion of pharmacotherapy prescription (ACEI or ARB, ß-blocker, or statin) at discharge. Additionally, SMuRF-less patients had a significantly higher rate of in-hospital all-cause mortality than patients with one or more SMuRF (883 [9·6%] vs 3411 [6·5%], p<0·0001). Myocardial infarction and heart failure at 30 days were lower in SMuRF-less patients. All-cause mortality remained increased in the SMuRF-less group for more than 8 years in men and up to the 12-year endpoint in women. INTERPRETATION: Individuals who present with STEMI in the absence of SMuRFs have a significantly increased risk of all-cause mortality, compared with those with at least one SMuRF, which was particularly evident in women. The increased early mortality rates are attenuated after adjustment for use of guideline-indicated treatments, highlighting the need for evidence-based pharmacotherapy during the immediate post-infarct period irrespective of perceived low risk. FUNDING: Swedish Heart and Lung Foundation, National Health and Medical Research Council (Australia).
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Quimioterapia/normas , Insuficiencia Cardíaca/mortalidad , Mortalidad Hospitalaria/tendencias , Infarto del Miocardio/mortalidad , Intervención Coronaria Percutánea/estadística & datos numéricos , Infarto del Miocardio con Elevación del ST/mortalidad , Antagonistas Adrenérgicos beta/uso terapéutico , Anciano , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/prevención & control , Quimioterapia/métodos , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/fisiopatología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia , Hipertensión/tratamiento farmacológico , Hipertensión/prevención & control , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Evaluación de Resultado en la Atención de Salud , Sistema de Registros , Estudios Retrospectivos , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/fisiopatología , Prevención del Hábito de Fumar/normas , Suecia/epidemiologíaRESUMEN
BACKGROUND: Bevacizumab-combined chemotherapy is a new regimen for advanced/recurrent endometrial cancer. AIMS: To evaluate the efficacy and safety of bevacizumab-combined chemotherapy in advanced/recurrent endometrial cancer. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Eligible studies were retrieved from Embase, PubMed, and Cochrane Library. The data of primary outcomes including progression-free survival and overall survival and secondary outcomes including overall survival, response rate, and adverse events (grade ≥2) were extracted, pooled, and used for the meta-analysis to compare the efficacy and safety of bevacizumab-combined chemotherapy with other treatments in patients with advanced/recurrent endometrial cancer. RESULTS: Notably, 2 randomized-controlled and 5 single-arm trials of bevacizumab-combined chemotherapy or bevacizumab single-agent therapy for endometrial cancer were included. Meta-analysis indicated that bevacizumab-combined chemotherapy significantly increased the progression-free survival rate (hazard ratio=0.82, 95% confidence interval=0.70, 0.97) and overall survival rate (hazard ratio=0.83, 95% confidence interval=0.70, 0.98) compared with chemotherapy alone. The rates of overall, complete, and partial response to bevacizumab-combined chemotherapy were 76%, 22%, and 21%, respectively. The 6 and 12-month disease-free progression rates after bevacizumab-combined chemotherapy were 79% and 62%, respectively. Anemia (23%), leukopenia (46%), neutropenia (51%), hypertension (16%), and fatigue (24%) were the general adverse events after bevacizumab-combined chemotherapy. CONCLUSION: Bevacizumab-combined chemotherapy may have a higher efficacy in improving the overall and progression-free survival in patients with advanced/recurrent endometrial cancers compared with chemotherapy alone.
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Bevacizumab/farmacología , Combinación de Medicamentos , Quimioterapia/normas , Neoplasias Endometriales/tratamiento farmacológico , Quimioterapia/métodos , Femenino , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricosRESUMEN
PURPOSE: This study aimed to compare the functioning, symptoms, and quality of life (QoL) of patients with breast or colon cancer before and after their first-cycle (FC) chemotherapy. DESIGN: One-group pretest/posttest design. METHOD: The study utilized the standardized Arabic-translated Quality of Life Questionnaire Version 3 from the European Organization for Research and Treatment of Cancer in measuring the functioning, symptoms, and QoL of 120 Saudi patients diagnosed with breast or colon cancer. Dependent t test was used in analyzing the presence of significant differences in mean scores before and after chemotherapy with periods ranging from 14 days to 21 days following the treatment protocol. RESULTS: The findings revealed significant differences in the functioning, symptoms, and QoL among patients with breast or colon cancer before and after FC chemotherapy (p < .001). Baseline scores showed higher physical, role, emotional, cognitive, and social functioning; lesser symptoms; lower financial difficulties; and better overall global health status compared to post-FC chemotherapy. CONCLUSION: Assessing the QoL of patients with breast or colon cancer undergoing FC chemotherapy is essential to establish a holistic care plan in supporting and alleviating the unfavorable effects of chemotherapy and implement patient-centered interventions that aid in the enhancement of their overall QoL.
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Neoplasias de la Mama/tratamiento farmacológico , Neoplasias del Colon/tratamiento farmacológico , Quimioterapia/psicología , Calidad de Vida/psicología , Adulto , Quimioterapia/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría/instrumentación , Psicometría/métodos , Arabia Saudita , Encuestas y CuestionariosRESUMEN
Standard treatment for classical Hodgkin lymphoma (cHL) is poorly tolerated in older patients and results disappointing. We assessed safety and efficacy of brentuximab vedotin (BV), in previously untreated patients with cHL unfit for standard treatment due to age, frailty or comorbidity. The primary outcome was complete metabolic response (CMR) by positron emission tomography/computed tomography after four BV cycles (PET4). The secondary outcomes included progression-free survival (PFS), overall survival (OS), and toxicity. In all, 35 patients with a median age of 77 years and median total Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score of 6 were evaluable for toxicity and 31 for response. A median of four cycles were given (range one-16). In all, 14 patients required dose reduction due to toxicity and 11 patients stopped treatment due to adverse events (AEs). A total of 716 AEs were reported, of which 626 (88%) were Grade 1/2 and 27 (77%) patients had at least one AE Grade ≥3. At PET4, CMR was 25·8% [95% confidence interval (CI) 13·7-42.2%] and objective response rate 83·9% (95% CI 63·7-90·8%). Median PFS was 7·3 months (95% CI 5·2-9·0), and OS 19·5 months. Our results suggest that BV monotherapy is tolerable but suboptimal in the front-line therapy of elderly or comorbid patients with cHL. Combining BV with other agents may be more effective. Trial Registration: Clinicaltrials.gov identifier: NCT02567851.
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Antineoplásicos Inmunológicos/uso terapéutico , Brentuximab Vedotina/uso terapéutico , Quimioterapia/normas , Fragilidad/epidemiología , Enfermedad de Hodgkin/tratamiento farmacológico , Factores de Edad , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/toxicidad , Biomarcadores de Tumor/metabolismo , Brentuximab Vedotina/administración & dosificación , Brentuximab Vedotina/efectos adversos , Brentuximab Vedotina/toxicidad , Comorbilidad , Relación Dosis-Respuesta a Droga , Quimioterapia/ética , Femenino , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/patología , Humanos , Masculino , Estadificación de Neoplasias/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Supervivencia sin Progresión , Seguridad , Resultado del Tratamiento , Reino Unido/epidemiologíaRESUMEN
Though the Quality Use of Medicines (QUM) principles have withstood the test of time, there are a number of challenges health care professionals face in today's society. An updated QUM framework would better reflect the current challenges we face.
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Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Quimioterapia/normas , Medicamentos Esenciales/uso terapéutico , Garantía de la Calidad de Atención de Salud , Anciano , Anciano de 80 o más Años , Australia , Depresión/psicología , Revisión de la Utilización de Medicamentos , HumanosAsunto(s)
Quimioterapia/métodos , Cuidados Preoperatorios/métodos , Radioterapia/métodos , Neoplasias Retroperitoneales/patología , Sarcoma/cirugía , Anciano , Estudios de Casos y Controles , Estudios de Cohortes , Quimioterapia/normas , Femenino , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Clasificación del Tumor/métodos , Estadificación de Neoplasias/métodos , Estudios Observacionales como Asunto , Readmisión del Paciente/estadística & datos numéricos , Cuidados Preoperatorios/mortalidad , Radioterapia/normas , Neoplasias Retroperitoneales/epidemiología , Estudios Retrospectivos , Sarcoma/mortalidad , Análisis de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
RATIONALE: Patients reporting high PD-L1 expression have shown to respond well to immunotherapy; however, some patients develop hyperprogressive disease upon initiation of immune checkpoint inhibitors. We report a patient with lung cancer and 100% PD-L1 expression who developed hyperprogressive disease while treated with pembrolizumab and responded well to salvage chemotherapy with carboplatin and pemetrexed. PATIENT CONCERNS: A 66-year-old African American female with 25-pack year smoking history, diabetes mellitus type 2, essential thrombocytosis, and a history of papillary thyroid carcinoma developed relapsed lung adenocarcinoma after 13 months of no evidence of disease. DIAGNOSIS: Surveillance imagine showed subcarinal and hilar lymphadenopathy, which was confirmed as recurrent lung adenocarcinoma via bronchoscopy. In addition, a brain scan showed a 5âmm enhancing left insular lesion. PD-L1 was reported as 100% expression. Staging was reported as stage IVB TxN3M1c lung adenocarcinoma. INTERVENTIONS: One fraction of radiation with a total dose of 20âGray was delivered to the left insular lesion. The patient initiated pembrolizumab (200âmg) every 3 weeks. She was then treated with salvage chemotherapy consisting of carboplatin (AUC 5) and pemetrexed (500âmg/m) every 3 weeks for 3 cycles. OUTCOMES: The brain lesion resolved after the radiation therapy. The patient developed hyperprogression with a large pericardial effusion and right pleural effusion after 2 treatments of pembrolizumab. Her PD-L1 expression decreased from 100% to 0% over a 10-week period. Salvage chemotherapy with carboplatin and pemetrexed resulted with 20 months of ongoing to evidence of disease. LESSONS: Immune checkpoint inhibitor-related hyperprogressive disease may respond to second-line salvage chemotherapy. Complete PD-L1 expression loss was observed after the patient's treatment and could be a marker of hyperprogressive disease or tumor immunoevasion.
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Antígeno B7-H1/análisis , Carcinoma de Pulmón de Células no Pequeñas/genética , Proteínas Serina-Treonina Quinasas/análisis , Quinasas de la Proteína-Quinasa Activada por el AMP , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antígeno B7-H1/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Quimioterapia/métodos , Quimioterapia/normas , Femenino , Expresión Génica/genética , Humanos , Proteínas Serina-Treonina Quinasas/genéticaRESUMEN
Importance: DNA repair gene aberrations occur in 20% to 30% of patients with castration-resistant prostate cancer (CRPC), and some of these aberrations have been associated with sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition platinum-based treatments. However, previous trials assessing platinum-based treatments in patients with CRPC have mostly included a biomarker-unselected population; therefore, efficacy in these patients is unknown. Objective: To characterize the antitumor activity of platinum-based therapies in men with CRPC with or without DNA repair gene alterations. Design, Setting, and Participants: In this case series, data from 508 patients with CRPC treated with platinum-based therapy were collected from 25 academic centers from 12 countries worldwide. Patients were grouped by status of DNA repair gene aberrations (ie, cohort 1, present; cohort 2, not detected; and cohort 3, not tested). Data were collected from January 1986 to December 2018. Data analysis was performed in 2019, with data closure in April 2019. Exposure: Treatment with platinum-based compounds either as monotherapy or combination therapy. Main Outcomes and Measures: The primary end points were as follows: (1) antitumor activity of platinum-based therapy, defined as a decrease in prostate-specific antigen (PSA) level of at least 50% and/or radiological soft tissue response in patients with measurable disease and (2) the association of response with the presence or absence of DNA repair gene aberrations. Results: A total of 508 men with a median (range) age of 61 (27-88) years were included in this analysis. DNA repair gene aberrations were present in 80 patients (14.7%; cohort 1), absent in 98 (19.3%; cohort 2), and not tested in 330 (65.0%; cohort 3). Of 408 patients who received platinum-based combination therapy, 338 patients (82.8%) received docetaxel, paclitaxel, or etoposide, and 70 (17.2%) received platinum-based combination treatment with another partner. A PSA level decrease of at least 50% was seen in 33 patients (47.1%) in cohort 1 and 26 (36.1%) in cohort 2 (P = .20). In evaluable patients, soft tissue responses were documented in 28 of 58 patients (48.3%) in cohort 1 and 21 of 67 (31.3%) in cohort 2 (P = .07). In the subgroup of 44 patients with BRCA2 gene alterations, PSA level decreases of at least 50% were documented in 23 patients (63.9%) and soft tissue responses in 17 of 34 patients (50.0%) with evaluable disease. In cohort 3, PSA level decreases of at least 50% and soft tissue responses were documented in 81 of 284 patients (28.5%) and 38 of 185 patients (20.5%) with evaluable disease, respectively. Conclusions and Relevance: In this study, platinum-based treatment was associated with relevant antitumor activity in a biomarker-positive population of patients with advanced prostate cancer with DNA repair gene aberrations. The findings of this study suggest that platinum-based treatment may be considered an option for these patients.
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Trastornos por Deficiencias en la Reparación del ADN/tratamiento farmacológico , Quimioterapia/normas , Compuestos de Platino/uso terapéutico , Neoplasias de la Próstata/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Docetaxel/uso terapéutico , Quimioterapia/métodos , Quimioterapia/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/uso terapéutico , Estudios RetrospectivosRESUMEN
BACKGROUND: At present, the effect of western-medicine (WM) therapy to treat diabetic peripheral neuropathy (DPN) is limited. Moxibustion is a representative external treatment in traditional Chinese medicine that has been beneficial to DPN. We aim to systematically assess the efficacy and safety of moxibustion in treating DPN, following PRISMA guidelines. METHODS: Eight electronic databases were searched to acquire information on eligible trials published from inception to June 1, 2019. We included randomized controlled trials (RCTs) applying moxibustion therapy with a minimum of 14-days treatment duration for DPN patients compared with placebo, no intervention, or conventional WM interventions. The primary outcomes in our study include the sensory-nerve conduction velocity (SNCV) and motor-nerve conduction velocity (MNCV). We used the Cochrane Collaboration Risk of Bias tool to assess the methodological quality of eligible RCTs. Statistical analyses were conducted using Review Manager 5.3. Risk ratios (RR) and mean differences (MD) were calculated with a 95% confidence interval (CI). The χ test was applied to assess the heterogeneity. RESULTS: In total, 11 RCTs were included that involved 927 DPN patients. Compared with the control group, there was an increase in median MNCV (MDâ=â6.26, 95% CI 2.64-9.89, Zâ=â3.39, Pâ=â.0007) and peroneal MNCV (MDâ=â6.45, 95% CI 5.30-7.61, Pâ<â.00001). There was also an increase in median SNCV (MDâ=â6.64, 95% CI 3.25-10.03, Pâ=â.0001) and peroneal SNCV (MDâ=â3. 57, 95% CI 2.06-5.09, Zâ=â4.63, Pâ<â.00001) in the treatment groups. The treatment groups receiving moxibustion therapy indicated a more significant improvement in total effectiveness rate (RRâ=â0.25, 95% CI 0.18-0.37, Zâ=â7.16, Pâ<â.00001). Toronto Clinical Scoring System indicated a significant decrease in the treatment groups (MDâ=â-2.12, 95% CI -2.82 to 1.43, Pâ<â.00001). Only 1 study reported that treatment groups experienced no adverse reactions. The other 10 studies did not mention adverse events. CONCLUSIONS: Moxibustion therapy may be an effective and safe option for DPN patients but needs to be verified in further rigorous studies.