RESUMEN
PD-L1 tumor expression is a widely used biomarker for patient stratification in PD-L1/PD-1 blockade anticancer therapies, particularly for lung cancer. However, the reliability of this marker is still under debate. Moreover, PD-L1 is widely expressed by many immune cell types, and little is known on the relevance of systemic PD-L1⺠cells for responses to immune checkpoint blockade. We present two clinical cases of patients with non-small cell lung cancer (NSCLC) and PD-L1-negative tumors treated with atezolizumab that showed either objective responses or progression. These patients showed major differences in the distribution of PD-L1 expression within systemic immune cells. Based on these results, an exploratory study was carried out with 32 cases of NSCLC patients undergoing PD-L1/PD-1 blockade therapies, to compare PD-L1 expression profiles and their relationships with clinical outcomes. Significant differences in the percentage of PD-L1⺠CD11b⺠myeloid cell populations were found between objective responders and non-responders. Patients with percentages of PD-L1⺠CD11b⺠cells above 30% before the start of immunotherapy showed response rates of 50%, and 70% when combined with memory CD4 T cell profiling. These findings indicate that quantification of systemic PD-L1⺠myeloid cell subsets could provide a simple biomarker for patient stratification, even if biopsies are scored as PD-L1 null.
Asunto(s)
Antígeno B7-H1/antagonistas & inhibidores , Biomarcadores de Tumor/metabolismo , Inmunoterapia , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antígeno B7-H1/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/metabolismoRESUMEN
PURPOSE: This study aims to determine the incidence of nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC), under medical practice conditions and the accuracy with which physicians perceive CINV. METHODS: Chemotherapy-naive patients receiving MEC between April 2012 and May 2013 were included. Patients completed a diary of the intensity of nausea and number of vomiting episodes. Complete response and complete protection were assessed as secondary endpoints. RESULTS: Of 261 patients included, 240 were evaluated. Median age was 64 years, 44.2 % were female and 11.2 % were aged less than 50 years; 95.3 % of patients received a combination of 5-hydroxytryptamine 3 (5-HT3) antagonist + corticosteroid as antiemetic treatment. Vomiting within 5 days of chemotherapy administration occurred in 20.8 %, nausea in 42 % and significant nausea in 23.8 % of patients. An increase in the percentage of patients with significant nausea (from 9.4 to 21.7 %) and vomiting (from 9.2 to 16.5 %) was observed from the acute to the delayed phase. Complete response was 84.2 % in the acute phase, 77 % in the late phase and 68.9 % in overall period. Complete protection was 79.5 % in the acute phase, 68.8 % in the late phase and 62.4 % throughout the study period. Physicians estimated prophylaxis would be effective for 75 % of patients receiving MEC, compared with 54.1 % obtained from patients' diary. CONCLUSION: Despite receiving prophylactic treatment, 31 % of patients did not achieve a complete response and 38 % complete protection. In general, nausea was worse controlled than vomiting. The results also showed the late phase was worse controlled than the acute phase in all variables. Healthcare providers overestimated the effectiveness of antiemetic prophylaxis.
Asunto(s)
Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Náusea/epidemiología , Vómitos/epidemiología , Antineoplásicos/uso terapéutico , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Incidencia , Quimioterapia de Inducción , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Médicos , Estudios Prospectivos , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológicoRESUMEN
OBJECTIVE: This study evaluates satisfaction with care (SC) in cancer patients treated at a Spanish day hospital to identify SC determinants and assess the relationship between SC and quality of life. METHODS: One hundred seventy-six patients with different tumour sites and disease stages completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the Cancer Outpatient Satisfaction with Care questionnaire for chemotherapy (OUT-PATSAT35 CT), the Oberst patients' perception of care quality and satisfaction scales, and an item on intention to recommend the hospital. Frequencies in the SC instruments, Spearman correlations between each scale of the OUT-PATSAT35 CT and overall satisfaction and between the subscales of OUT-PATSAT35 CT and of QLQ-C30 were calculated, and the determinants of patients' SC were calculated through multivariate regression models. RESULTS: Satisfaction with care was high: mean scores were >70 in all OUT-PATSAT35 CT areas except doctor availability and environment. These scores were in line with the other SC instruments. Correlation with overall satisfaction was high and statistically significant (p < 0.01) for all subscales, especially for the nurses domain, which also had higher SC scores. Correlations between the EORTC QLQ-C30 and the OUT-PATSAT35 CT were low (≤ 0.35). Younger patients and those with breast cancer showed significantly lower satisfaction in most subscales. Unmarried patients and patients that had undergone surgery reported lower satisfaction only in specific subscales. CONCLUSIONS: Satisfaction with care among cancer patients treated at the day hospital is high. Nurses play a key and successful role. Age and tumour location revealed stronger relationships with SC. Correlations between SC and quality of life indicate that these concepts are complementary.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Pacientes Ambulatorios/estadística & datos numéricos , Satisfacción del Paciente/estadística & datos numéricos , Calidad de Vida/psicología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estado de Ejecución de Karnofsky , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias/psicología , Pacientes Ambulatorios/psicología , Relaciones Profesional-Paciente , Psicometría , Calidad de la Atención de Salud , Reproducibilidad de los Resultados , Factores Sexuales , Factores Socioeconómicos , España , Encuestas y CuestionariosRESUMEN
PURPOSE: The OUT-PATSAT35 CT questionnaire evaluates satisfaction with care expressed by cancer outpatients receiving chemotherapy. This study assesses the psychometric properties of the OUT-PATSAT35 CT when applied to a sample of Spanish patients. METHODS: One hundred seventy-six patients with different tumour sites and disease stages completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-C30, the OUT-PATSAT35 CT, the Oberst patients' perception of care quality and satisfaction scales (OS) and the item on intention to recommend the hospital (IR). Psychometric evaluation of the structure, reliability and validity of the questionnaire was conducted. RESULTS: Multitrait scaling analysis showed that 32 of 34 item-scale correlation coefficients met the standards for convergent validity and that many of them met the standards for discriminant validity. Cronbach's coefficients were good (0.78-0.97) for all scales except doctor availability and environment. Correlations between the QLQ-C30 and the OUT-PATSAT35 CT were low (≤0.40). Correlations between IR and the OUT-PATSAT35 CT were moderate, and correlations between this questionnaire and the OS were fairly low. Areas whose contents were more related had higher correlation coefficients (>0.50) and vice versa (<0.1). Male patients, elderly patients, those with higher education levels, those with higher scores in four OS and patients who had not received surgery showed higher satisfaction with care in several OUT-PATSAT35 CT areas. CONCLUSIONS: The OUT-PATSAT35 CT is a reliable and valid instrument when applied to a sample of Spanish cancer patients. These results are in line with those of the validation study conducted by the authors of the questionnaire and with the validation study for Spain of the OUT-PATSAT35 RT.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Pacientes Ambulatorios/estadística & datos numéricos , Satisfacción del Paciente/estadística & datos numéricos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/psicología , Pacientes Ambulatorios/psicología , Relaciones Profesional-Paciente , Psicometría/instrumentación , Reproducibilidad de los Resultados , Factores Sexuales , España , Encuestas y CuestionariosRESUMEN
OBJECTIVE: We assessed trabectedin in patients with advanced uterine leiomyosarcoma (uLMS) in real-life clinical practice given according to the marketing authorization. METHODS: Thirty-six women from 11 tertiary hospitals across Spain who received trabectedin after anthracycline-containing regimen/s were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). RESULTS: Median PFS and overall survival (OS) since starting trabectedin treatment were 5.4 (95%CI: 3.5-7.3) and 18.5 months (95%CI: 11.5-25.6), respectively. Median OS was significantly higher (P = 0.028) in patients receiving trabectedin in ≤ 2nd line (25.3 months) than in ≥ 3rd (15.1 months) and with ECOG performance status ≤ 1 at trabectedin start (19.8 months) than ECOG 2-3 (6.0 months, P = 0.013). When calculating OS since diagnosis, patients had longer OS with localized disease at diagnosis (87.4 months) vs. locally advanced (30.0 months) or metastatic (44.0 months, P = 0.041); and patients who received adjuvant therapy (87.4 months) compared with those who did not (30.0 months, P = 0.003), especially when receiving radiochemotherapy (106.7 months, P = 0.027). One patient (2.8%) had a complete response (CR) and nine patients (25.0%) achieved a partial response (PR) for an objective response rate of 27.8% with median response duration of 11 months (range: 4-93). Eighteen patients (50.0%) had disease stabilization for a disease control rate (DCR) of 77.8%. More patients receiving trabectedin in 1st-line of advanced disease achieved CR (16.7%) and PR (50.0%) than those in ≥ 2nd line/s (0.0% and 20.0%), whereas the DCR was similar across treatment lines. Reversible neutropenia was the most common grade 3/4 laboratory abnormality (19.4%). CONCLUSIONS: Trabectedin confers clinical benefit in patients with recurrent/metastatic uLMS, given after failure to an anthracycline-based regimen being comparable to those reported in clinical trials and with a manageable safety profile.
RESUMEN
The majority of lung cancer patients progressing from conventional therapies are refractory to PD-L1/PD-1 blockade monotherapy. Here, we show that baseline systemic CD4 immunity is a differential factor for clinical responses. Patients with functional systemic CD4 T cells included all objective responders and could be identified before the start of therapy by having a high proportion of memory CD4 T cells. In these patients, CD4 T cells possessed significant proliferative capacities, low co-expression of PD-1/LAG-3 and were responsive to PD-1 blockade ex vivo and in vivo. In contrast, patients with dysfunctional systemic CD4 immunity did not respond even though they had lung cancer-specific T cells. Although proficient in cytokine production, CD4 T cells in these patients proliferated very poorly, strongly co-upregulated PD-1/LAG-3, and were largely refractory to PD-1 monoblockade. CD8 immunity only recovered in patients with functional CD4 immunity. T-cell proliferative dysfunctionality could be reverted by PD-1/LAG-3 co-blockade. Patients with functional CD4 immunity and PD-L1 tumor positivity exhibited response rates of 70%, highlighting the contribution of CD4 immunity for efficacious PD-L1/PD-1 blockade therapy.
Asunto(s)
Antígeno B7-H1/inmunología , Linfocitos T CD4-Positivos/inmunología , Inmunidad Celular , Memoria Inmunológica , Inmunoterapia , Neoplasias Pulmonares , Proteínas de Neoplasias/inmunología , Receptor de Muerte Celular Programada 1/inmunología , Células A549 , Anciano , Linfocitos T CD4-Positivos/patología , Femenino , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana EdadRESUMEN
Immunotherapy has radically transformed the management of metastatic malignant melanoma. Ipilimumab, a CTLA-4-targeted monoclonal antibody, was the first immunotherapeutic drug to reach a survival benefit compared with traditional chemotherapy. PD-1 targeted therapies, pembrolizumab and nivolumab, have demonstrated, in recent clinical trials, to be even more effective and safer. PD-1 and CTLA-4 blockade combination appears to improve the outcomes achieved so far, although increasing toxicity. However, many questions concerning the optimal timing of administration or the most adequate sequence of treatment are yet to be answered.
RESUMEN
Gastrointestinal stromal tumours (GIST) are the most common mesenchymal neoplasm of the gastrointestinal tract. Rectum localisation is infrequent for these neoplasms, accounting for about 5% of all cases. Distant metastases of GIST are also rare. We present a patient with special features: the tumour is localised in rectum and it has an uncommon metastatic site, the skull, implying a complex differential diagnosis approach.