Bempegaldesleukin (BEMPEG; NKTR-214) efficacy as a single agent and in combination with checkpoint-inhibitor therapy in mouse models of osteosarcoma.

Survival of patients with relapsed/refractory osteosarcoma has not improved in the last 30 years. Several immunotherapeutic approaches have shown benefit in murine osteosarcoma models, including the anti-programmed death-1 (anti-PD-1) and anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) immune checkpoint inhibitors. Treatment with the T-cell growth factor interleukin-2 (IL-2) has shown some clinical benefit but has limitations due to poor tolerability. Therefore, we evaluated the efficacy of bempegaldesleukin (BEMPEG; NKTR-214), a first-in-class CD122-preferential IL-2 pathway agonist, alone and in combination with anti-PD-1 or anti-CTLA-4 immune checkpoint inhibitors in metastatic and orthotopic murine models of osteosarcoma. Treatment with BEMPEG delayed tumor growth and increased overall survival of mice with K7M2-WT osteosarcoma pulmonary metastases. BEMPEG also inhibited primary tumor growth and metastatic relapse in lungs and bone in the K7M3 orthotopic osteosarcoma mouse model. In addition, it enhanced therapeutic activity of anti-CTLA-4 and anti-PD-1 checkpoint blockade in the DLM8 subcutaneous murine osteosarcoma model. Finally, BEMPEG strongly increased accumulation of intratumoral effector T cells and natural killer cells, but not T-regulatory cells, resulting in improved effector:inhibitory cell ratios. Collectively, these data in multiple murine models of osteosarcoma provide a path toward clinical evaluation of BEMPEG-based regimens in human osteosarcoma.

Cirugía del carcinoma mamario revisión de 20 años / Surgery of breast cancer twenty years review

Exponer los diferentes tratamientos quirúrgicos del carcinoma de mama realizados en los últimos veinte años y las características clínico-patológicas tumorales. Estudio descriptivo, retrospectivo de pacientes vistos en el lapso comprendido entre junio de 1990 a diciembre de 2009. Se evaluó la procedencia, edad, mama afectada, cuadrante, forma de diagnóstico, tipo histológico, estadio clínico, tratamiento, intervalo libre de enfermedad, recidiva, tiempo de seguimiento. 446 casos, edad promedio 54,91 años (DS± 13,03, rango 22 - 91 años). La mama izquierda presentó lesión tumoral más frecuente. Predominó estadio II. Tipo histológico mayoritario fue carcinoma ductal infiltrante. Los casos avanzados recibieron quimioterapia neoadyuvante, la mayoría de los demás tratamiento adyuvante. El procedimiento quirúrgico fue variable entre mastectomía parcial oncológica, mastectomía radical modificada, cirugía oncoplástica, predominando la primera con 55,83%. El 4,41% de los pacientes presentó recidivas locales, intervalo libre de enfermedad fue 34,52 meses (DS ± 11,31 rango, 10 - 130) después del tratamiento quirúrgico. En relación al seguimiento, se mantienen 408 pacientes (91,47%), con una media de 54,34 meses (DS ± 48,21, rango 1-240 meses) fallecieron 78 pacientes, 22 por comorbilidad (5,39%) y 56 por el cáncer (13,72%), el tiempo de sobrevida fue 42,40 meses (DS ± 25,62, rango 10-132 m.). El carcinoma de mama presenta una historia natural variable, heterogénea, aún después del tratamiento quirúrgico y adyuvante, hay que evitar que la lesión neoplásica progrese a estadios avanzados, y podamos efectuar un diagnóstico temprano

Discuss the different surgical treatments of breast cancer conducted in the last twenty years and clinical and pathological tumor characteristics. We performed descriptive, retrospective study of patients by diagnosis of mammary carcinoma seen in June 1990 to December 2009. The variables were evaluated: origin, age, affected breast, quadrant, form of diagnosis, histological type, clinical stage, treatment, free interval of disease, recurrence, follow-up time. Review 446 cases, the average age was 54.91 years (STD +/- 13.03, range 22 to 91). The left breast made the tumor more frequently. More than half of patients were in stage II at diagnosis. The predominant histological type was infiltrating ductal carcinoma without other specification. More patients received neo-adjuvant and adjuvant chemotherapy. The surgicalprocedure varied between partial oncologic mastectomies, modified radical mastectomy, oncoplastic surgery, dominating the first one with 55.83 %. 4.41 % the patients had local relapses with a free interval disease of 34.52 months (STD +/- 11.31 r: 10-130) after surgical treatment. Follow-up has been achieving 408 patients (91.47 %), the average was 54.34 month (Std +/- 48.21, range 1-240 m). 78 patients died, 22 for comorbility (5.39 %) and 56 for the cancer (13.72%), the survival average time was 42.40 months (STD +/- 25.62, range 10-132 m). The breast cancer presents highly variable natural history even after surgical and the adjuvant treatment; we must prevent the neoplastic lesion to progress to advanced stages. Early diagnosis is very important