The S-REAL study: Spanish real-world data on unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy.

OBJECTIVES: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP). METHODS: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI). RESULTS: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients. CONCLUSIONS: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.

Updated Review and Clinical Recommendations for the Diagnosis and Treatment of Patients with Retroperitoneal Sarcoma by the Spanish Sarcoma Research Group (GEIS).

Soft tissue sarcomas (STS) are an uncommon and biologically heterogeneous group of tumors arising from mesenchymal cells. The incidence is estimated at five cases per 100,000 people per year. Retroperitoneal sarcomas (RPS) account for 10-15% of all STS, and their management depends on their anatomical characteristics and histotype. Due to their very low incidence, it is recommended that RPS be treated in reference centers and evaluated by an experienced multidisciplinary team (MDT). In Spain, the Spanish Group for Research in Sarcomas (GEIS) brings together experts from various specialties to promote research on sarcomas and improve treatment results. This paper summarizes the GEIS recommendations for the diagnosis, treatment, and follow-up of patients with RPS.

Identification of ALK-positive patients with advanced NSCLC and real-world clinical experience with crizotinib in Spain (IDEALK study).

OBJECTIVES: To determine the incidence of ALK translocations in patients with advanced/metastatic NSCLC in Spain, to describe the clinical characteristics of these patients, and to evaluate the effectiveness and safety of treatment with crizotinib in a real-world setting. METHODS: This is an observational prospective and retrospective cohort study to determine the incidence of ALK translocations and to analyze the effectiveness and safety of crizotinib in a real-world setting. Patient characteristics, treatment patterns, time to best overall response, duration of treatment, objective response rates (ORR), rates of adverse events (AE), progression free survival (PFS) and overall survival (OS) were evaluated in the ALK study cohort of patients treated with crizotinib (prospective and retrospective). ALK incidence and quality of life (QoL) questionnaires were measured from patients included in the prospective cohort. RESULTS: The incidence of ALK translocations was 5.5 % (31 of 559 patients). Compared with ALK-negative patients, ALK-positive patients were significantly younger, predominantly female, and non-smokers. In the crizotinib effectiveness and safety study, 91 patients (42 prospective, 49 retrospective) with ALK-positive NSCLC (43.9 % in first-line, 56.1 % in second or more lines) were included. The ORR was 59.3 % and the median duration of response was 13.5 months (IQR, 5.3-26.2). The median PFS was 15.8 months (95 % CI, 11.8-22.3) and the median OS was 46.5 months, with 53 patients (58.2 %) still alive at data cut-off date. Frequently reported AEs included elevated transaminases, gastrointestinal disorders, and asthenia. Most patients (76.5 %) reported improved or stable scores for global QoL during treatment. CONCLUSIONS: The observed incidence of ALK translocations in NSCLC patients is aligned with published reports. This analysis of the real-world clinical experience in Spain confirms the therapeutic benefit and safety of crizotinib in advanced/metastatic ALK-positive NSCLC. CLINICALTRIALS: gov: NCT02679170.

A Multicenter Analysis of the Outcome of Cancer Patients with Neutropenia and COVID-19 Optionally Treated with Granulocyte-Colony Stimulating Factor (G-CSF): A Comparative Analysis.

BACKGROUND: Approximately 15% of patients infected by SARS-CoV-2 develop a distress syndrome secondary to a host hyperinflammatory response induced by a cytokine storm. Myelosuppression is associated with a higher risk of infections and mortality. There are data to support methods of management for neutropenia and COVID-19. We present a multicenter experience during the first COVID-19 outbreak in neutropenic cancer patients infected by SARS-CoV-2. METHODS: Clinical retrospective data were collected from neutropenic cancer patients with COVID-19. Comorbidities, tumor type, stage, treatment, neutropenia severity, G-CSF, COVID-19 parameters, and mortality were analyzed. A bivariate analysis of the impact on mortality was carried out. Additionally, we performed a multivariable logistic regression to predict respiratory failure and death. RESULTS: Among the 943 cancer patients screened, 83 patients (11.3%) simultaneously had neutropenia and an infection with COVID-19. The lungs (26%) and breasts (22%) were the primary locations affected, and most patients had advanced disease (67%). In the logistic model, as adjusted covariates, sex, age, treatment (palliative vs. curative), tumor type, and the lowest level of neutrophils were used. A significant effect was obtained for the number of days of G-CSF treatment (OR = 1.4, 95% CI [1,1,03,92], p-value = 0.01). CONCLUSIONS: Our findings suggest that a prolonged G-CSF treatment could be disadvantageous for these cancer patients with infections by COVID-19, with a higher probability of worse outcome.

Simultaneous diagnosis of liver PEComa in a family with known Li-Fraumeni syndrome: a case report.

BACKGROUND: Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary disease. It is associated with the loss of function of the p53 protein and an increased risk of malignant tumor development at early age. The most frequently detected tumors include breast cancer, sarcomas, leukemia, brain tumors, and adrenocortical carcinomas. While sarcomas account for only 1% of solid tumors, they are more frequently detected in these families. CASE PRESENTATION: We report a simultaneous diagnosis of hepatic perivascular epithelioid cell tumor (PEComa), a very rare subtype of sarcoma, in two siblings with a LFS. CONCLUSIONS: The simultaneous diagnosis of PEComa in two siblings presented in this case allowed us to review the frequency of PEComa in this genetic syndrome previously reported, which was very little. Despite its rarity, PEComa must be considered in the differential diagnosis of new-onset liver lesions in patients who were previously diagnosed with LFS.

FGF21 and its Relationship with Inflammatory and Metabolic Parameters in HIV Patients after Antiretroviral Treatment.

BACKGROUND: Fibroblast Growth Factor 21 (FGF21) serum levels are associated with insulin resistance and metabolic syndrome in HIV patients. OBJECTIVE: To quantify FGF21 levels in HIV patients using antiretroviral therapy (ART) and to analyze a possible association between serum FGF21 levels and lipid profile, levels of proinflammatory cytokines, and atherogenic risk factors. MATERIALS AND METHODS: Twenty patients with HIV infection, who received ART in a scheme consisting of Tenofovir/Emtricitabine+Lopinavir/Ritonavir, were enrolled in this study. The serum levels of FGF21, inflammatory parameters (IL-6 and IL-1ß), glucose, cholesterol, triglycerides, and insulin were determined at baseline and after 36 weeks of treatment. The homeostatic model assessment for insulin resistance (HOMA-IR) and the atherogenic risk factor were also calculated. RESULTS: After 36 weeks, serum FGF21 levels decreased significantly (p=0.011), whereas IL-6 levels (r=0.821, p=0.0001) and the CD4+ T cell count (r=0.446, p=0.048), showed a positive correlation with the decrease in FGF21 levels. There was an increase in total cholesterol (r=-0.483, p=0.031), LDL (r=-0.496, p=0.026), VLDL (r=-0.320, p=0.045), and the atherogenic index factor (r=-0.539, p=0.014), these values showed a negative correlation with FGF21 levels. CONCLUSION: The decrease of serum FGF21 levels due to ART is associated with the alteration in lipid profile and an increased risk for cardiovascular diseases. These variations are predictors of inflammatory status in HIV patients using antiretroviral therapy.

Actualización en el manejo de sarcomas retroperitoneales y pélvicos; el papel de la cirugía compartimental / Update in pelvic and retroperitoneal sarcoma management: The role of compartment surgery

La cirugía de los sarcomas retroperitoneales debe ser compartimental «en bloque», lo que implica la resección de órganos adyacentes al tumor. Su empleo «de entrada» permite un elevado porcentaje de resecciones con márgenes negativos, lo que supone un mejor control local y mayor supervivencia en muchos pacientes. La preservación de órganos debe hacerse de forma personalizada, especialmente en la pelvis, y adaptarla a la agresividad histológica del tumor. La biopsia preoperatoria permite establecer el subtipo de sarcoma y una adecuada estrategia perioperatoria. Estos pacientes deben ser manejados por cirujanos expertos en centros de referencia, con unidades multidisciplinarias y comités oncológicos. El uso de quimioterapia y radioterapia aún no está bien definido, por lo que solo se recomienda en centros de referencia con ensayos clínicos. En la actualidad esta es la única opción para ofrecer las mejores tasas de morbimortalidad, y las posibles mejoras en la supervivencia de estos pacientes

Surgery for retroperitoneal sarcomas should be "en bloc" compartmental, which involves resection of unaffected organs. Its upfront use is key, providing a high percentage of resections with negative margins, resulting in a better local control and increased survival in many patients. Preservation of organs should be done in an individualized manner, especially in the pelvic location, and adapted to the histological aggressiveness of the tumor. Preoperative biopsy is able to establish the diagnosis of sarcoma subtype and consequently an adequate perioperative strategy. These patients should be managed by expert surgeons at referral centers with multidisciplinary units and oncology committees. The use of chemotherapy and radiotherapy is not yet well defined, so it is only recommended at referral centers with clinical trials. Currently, this is the only option to offer the best morbidity and mortality rates, as well as possible improvements in the survival of these patients

Update in pelvic and retroperitoneal sarcoma management: The role of compartment surgery. / Actualización en el manejo de sarcomas retroperitoneales y pélvicos; el papel de la cirugía compartimental.

Surgery for retroperitoneal sarcomas should be "en bloc" compartmental, which involves resection of unaffected organs. Its upfront use is key, providing a high percentage of resections with negative margins, resulting in a better local control and increased survival in many patients. Preservation of organs should be done in an individualized manner, especially in the pelvic location, and adapted to the histological aggressiveness of the tumor. Preoperative biopsy is able to establish the diagnosis of sarcoma subtype and consequently an adequate perioperative strategy. These patients should be managed by expert surgeons at referral centers with multidisciplinary units and oncology committees. The use of chemotherapy and radiotherapy is not yet well defined, so it is only recommended at referral centers with clinical trials. Currently, this is the only option to offer the best morbidity and mortality rates, as well as possible improvements in the survival of these patients.

Optimization of the Therapeutic Approach to Patients with Sarcoma: Delphi Consensus.

Soft tissue sarcomas (STS) constitute a heterogeneous group of rare solid tumors associated with significant morbidity and mortality. The evaluation and treatment of STS require a multidisciplinary team with extensive experience in the management of these types of tumors. National and international clinical practice guidelines for STS do not always provide answers to a great many situations that specialists have to contend with in their everyday practice. This consensus provides a series of specific recommendations based on available scientific evidence and the experience of a group of experts to assist in decision-making by all the specialists involved in the management of STS.

Pharmaceutical services in a Mexican pain relief and palliative care institute

Neither the purchase nor the distribution of pharmaceuticals in hospitals and community pharmacies in Mexico is under the care of pharmacists. Some are under control of physicians. This report presents the results of the implementation of some of pharmaceutical services for the Jalisco Pain Relief, and Palliative Care Institute (Palia Institute), under the direction of the Secretary of Health, Government of Jalisco. The services implemented were drug distribution system, Drug Information Service, Pharmacovigilance Program , and home pharmacotherapy follow-up pilot program for patients with advanced illness, with the ultimate using the appropriate medication. The drug distribution system included dispensing of opioid pain medications, antidepressants, anticonvulsants, NSAIDs, anxiolytic drugs, steroid drugs, laxatives, and anti-emetics. The frequently used drugs were morphine sulfate (62%), amitriptyline (6.4%), and dextropropoxyphene (5.8%). The Drug Information Service answered 114 consultations, mainly asked by a physician (71%) concerned with adverse drug reactions and contraindications (21%). The pharmacovigilance program identified 146 suspected adverse drug reactions and classified them reasonably as possible (27%), probable (69%), and certain (4%). These were attributed mainly to pregabalin and tramadol. The home pharmacotherapy follow-up pilot program cared patients with different cancer diagnoses and drug-related problems (DRP), which were identified and classified (according to second Granada Consensus) for pharmaceutical intervention as DRP 1 (5%), DRP 2 (10%), DRP 3 (14%), DRP 4 (19%), DRP 5 (24%), or DRP 6 (28%). This report provides information concerning the accurate use of medication and, above all, an opportunity for Mexican pharmacists to become an part of health teams seeking to resolve drug-related problems (AU)

En México, ni la compra ni la distribución de medicamentos en hospitales y farmacias comunitarias están bajo el cuidado de farmacéuticos. Unos cuantos están a cargo de médicos. Este artículo presenta los resultados de la implementación de algunos servicios farmacéuticos en el Instituto Jaliscience de Alivio al Dolor y Cuidados Paliativos (Instituto Palia), bajo la dirección de la Secretaría de Salud del Gobierno de Jalisco. Los servicios implementados fueron un sistema de distribución de medicamentos, un Servicio de Información de Medicamentos, un programa de Farmacovigilancia, y un programa piloto de seguimiento farmacoterapéutico domiciliario para pacientes con enfermedad avanzada, con el objetivo de utilizar la medicación apropiada. El sistema de distribución de medicamentos incluyó la dispensación de analgésicos opiáceos, antidepresivos, anticonvulsivantes, AINEs, ansiolíticos, esteroides, laxantes y antieméticos. Los más utilizados fueron sulfato de morfina (62%), amitriptilina (6,4%) y dextropropoxifeno (5,8%). El Servicio de Información de Medicamentos respondió a 114 consultas realizadas principalmente por un médico, concernientes a reacciones adversas (71%) y contraindicaciones (21%). El programa de Farmacovigilancia identificó 146 sospechas de reacciones adversas y las clasificó como posible (27%), probable (69%), y seguras (4%). Se atribuyeron principalmente a pregabalina y tramadol. El programa piloto de seguimiento farmacoterapéutico domiciliario atendió pacientes con diferentes diagnósticos de cáncer y se identificaron problemas relacionados con medicamentos que se clasificaron (según el Segundo Consenso de Granada) como PRM 1(5%), PRM 2 (10%), PRM 3 (14%), PRM 4 (19%), PRM 5 (24%), o PRM 6 (28%). Este artículo proporciona información relacionada al uso adecuado de medicamentos y, sobre todo ofrece una oportunidad para que los farmacéuticos mexicanos lleguen a ser parte del equipo de salud tratando de resolver los problemas relacionados con medicamentos (AU)

Pharmaceutical services in a Mexican pain relief and palliative care institute.

Neither the purchase nor the distribution of pharmaceuticals in hospitals and community pharmacies in Mexico is under the care of pharmacists. Some are under control of physicians. This report presents the results of the implementation of somef pharmaceutical services for the Jalisco Pain Relief, and Palliative Care Institute (Palia Institute), under the direction of the Secretary of Health, Government of Jalisco. The services implemented were drug distribution system, Drug Information Service, Pharmacovigilance Program, and home pharmacotherapy follow-up pilot program for patients with advanced illness, with the ultimate using the appropriate medication. The drug distribution system included dispensing of opioid pain medications, antidepressants, anticonvulsants, NSAIDs, anxiolytic drugs, steroid drugs, laxatives, and anti-emetics. The frequently used drugs were morphine sulfate (62%), amitriptyline (6.4%), and dextropropoxyphene (5.8%). The Drug Information Service answered 114 consultations, mainly asked by a physician (71%) concerned with adverse drug reactions and contraindications (21%). The pharmacovigilance program identified 146 suspected adverse drug reactions and classified them reasonably as possible (27%), probable (69%), and certain (4%). These were attributed mainly to pregabalin and tramadol. The home pharmacotherapy follow-up pilot program cared patients with different cancer diagnoses and drug-related problems (DRP), which were identified and classified (according to second Granada Consensus) for pharmaceutical intervention as DRP 1 (5%), DRP 2 (10%), DRP 3 (14%), DRP 4 (19%), DRP 5 (24%), or DRP 6 (28%). This report provides information concerning the accurate use of medication and, above all, an opportunity for Mexican pharmacists to become an part of health teams seeking to resolve drug-related problems.