Barriers to receipt of novel oral oncolytics: A single-institution quality improvement investigation.

INTRODUCTION: Novel oral oncolytic agents have become the standard of care and first-line therapies for many malignancies. However, issues impacting access to these drugs are not well explored. As part of a quality improvement project in a large tertiary academic institution, we aim to identify potential barriers that delay treatment for patients who are prescribed novel oral oncolytics. METHODS: This was a retrospective review of adults who were newly prescribed a novel oral oncolytic for Food and Drug Administration-approved indications at a single tertiary care center. Patients were identified via electronic prescription data (e-Scribe). Demographics, insurance information, and prescription dates were extracted from the electronic medical record and pharmacy claims data. Statistical analyses were performed to determine whether time-to-receipt was associated with insurance category, pharmacy transfers, cost assistance, and drug prescribed. RESULTS: Of the 270 successfully filled prescriptions, the mean time-to-receipt was 7.3 ± 10.3 days (range: 0-109 days). Patients with Medicare experienced longer time-to-receipt (9.1 ± 13.1 days) compared to patients with commercial insurance (4.4 ± 3.3). Uninsured patients experienced the longest time-to-receipt (15.7 ± 7.8 days) overall. Pharmacy transfers and cost assistance programs were also significantly associated with longer time-to-receipt. Ten prescriptions remained unfilled 90 days after the study period and were considered abandoned. CONCLUSION: Insurance has a significant effect on the time-to-receipt of newly prescribed novel oral oncolytics. Pharmacy transfers and applying for cost assistance are also associated with longer wait times for patients. Our retrospective analysis identifies areas of improvement for future interventions to reduce wait times for patients receiving novel oral oncolytics.

Papiledema como primera manifestación de trombosis de senos venosos en un paciente pediátrico. Reporte de caso y revisión de literatura / Papilledema as an initial finding in venous sinus thrombosis in a child. Case report and literature review

Introducción: la trombosis de senos venosos (TSV) en niños, sin factores de riesgo es una patología rara pero potencialmente fatal. La cefalea es el síntoma principal y muy pocos pacientes se presentan sin este. El papiledema como hallazgo inicial se presenta sólo en el 9% de los pacientes. Presentamos el caso de una menor de 13 años, sin factores de riesgo para TSV, cuya manifestación inicial fue el papiledema en ausencia de cefalea. Objetivo: describir el caso clínico de una paciente menor de edad sin comorbilidades, factores de riesgo ni cefalea, con papiledema como única manifestación de TSV. Diseño de estudio: reporte de caso. Resumen del caso: menor de 13 años, sin antecedentes, con cuadro clínico de 12 horas de evolución de dolor en ojo derecho de instauración progresiva, tipo punzada, asociado a visión doble y un episodio emético. Al examen físico con agudeza visual (AV) 20/20 en ambos ojos, con papiledema; sin hallazgos positivos al examen neurológico ni en otros sistemas. Conclusión: La TSV en pacientes pediátricos sin factores de riesgo ni cefalea es rara. El papiledema es uno de los hallazgos principales de esta patología y en pocas ocasiones es la manifestación inicial. Es importante conocer los síntomas y signos oft almológicos de la TSV, ya que pueden ser el único hallazgo en esta patología.

Background: venous sinus thrombosis (VST) in children, without risk factors, is a rare but potentially fatal pathology. Headache is the main symptom and only few patients present without it. Papilledema as an initial finding occurs only in 9% of patients. We present the case of a 13 years old girl, without risk factors for VST, with papilledema as initial manifestation in the absence of headache. Objective: to describe a clinical case of with venous sinus thrombosis without comorbidities or risk factors, who had papilledema as first symptom. Study design: case report and literature review. Case summary: 13 years old girl, without medical history, with a clinical picture of 12 hours of right eye progressive pain, prick type, associated with double vision and an emetic episode. Physical examination with visual acuity (VA) 20/20 in both eyes and papilledema; without positive findings in the neurological examination or in other systems. Conclusion: venous sinus thrombosis in pediatric patients without risk factors or headache is rare. Papilledema is one of the main fi ndings of this pathology and in few cases it is the initial manifestation. It is important to know the symptoms and ophthalmological signs of VST because it could be the only finding in this pathology.

A pilot study of durvalumab and tremelimumab and immunogenomic dynamics in metastatic breast cancer.

Immune checkpoint inhibitors produce modest responses in metastatic breast cancer, however, combination approaches may improve responses. A single arm pilot study was designed to determine the overall response rate (ORR) of durvalumab and tremelimumab, and evaluate immunogenomic dynamics in metastatic endocrine receptor (ER) positive or triple negative breast cancer (TNBC). Simon two-stage design indicated at least four responses from the first 18 patients were needed to proceed with the second stage. T-cell receptor (TCR) sequencing and immune-gene expression profiling were conducted at baseline and two months, whole exome sequencing was conducted at baseline. Eighteen evaluable patients were accrued (11 ER-positive; seven TNBC). Only three patients had a response (ORR = 17%), thus the study did not proceed to the second stage. Responses were only observed in patients with TNBC (ORR = 43%). Responders versus non-responders had upregulation of CD8, granzyme A, and perforin 1 gene expression, and higher mutational and neoantigen burden. Patients with TNBC had an oligoclonal shift of the most abundant TCR-beta clonotypes compared to those with ER-positive disease, p = 0.004. We conclude responses are low in unselected metastatic breast cancer, however, higher rates of clinical benefit were observed in TNBC. Immunogenomic dynamics may help identify phenotypes most likely to respond to immunotherapy.

Resección de melanoma palpebral por técnica de Mohs y reconstrucción palpebral: Reporte de caso / Resection of melanoma of the eyelid by Mohs technique and eyelid reconstruction. Case Report

Objetivo: Describir el cuadro clínico de un paciente con diagnóstico de melanoma in situ en párpado inferior del ojo derecho con compromiso de conjuntiva tarsal y de vía lagrimal, llevado a cirugía micrográfica de Mohs diferida y posteriormente reconstrucción de párpado inferior e intubación de la vía lagrimal. Diseño: Reporte de caso. Estudio descriptivo y retrospectivo. Metodología: Con el propósito de comparar la técnica quirúrgica empleada y otras posibilidades de manejo satisfactorio, se realizó la búsqueda, revisión y análisis de literatura referente al diagnóstico patológico y al tratamiento quirúrgico descrito. Descripción: Paciente de 69 años quien presento cuadro clínico de tres años de evolución de lesión palpebral melanótica con compromiso de borde palpebral y conjuntiva tarsal. La biopsia inicial reportó lentigo solar. Por el crecimiento y pigmentación progresiva de la lesión se realizó una segunda biopsia que confirmó el diagnóstico de melanoma in situ. Se decidió llevar el paciente a cirugía micrográfica de Mohs diferida y posterior reconstrucción palpebral por parte de cirujano oculoplástico. Discusión: El melanoma es un tumor maligno desarrollado a partir de la degeneración de los melanocitos. Es además la primera causa de muerte por lesiones malignas en la piel y su tasa de incidencia ha incrementado significativamente en la última década. Una gran variedad de métodos se ha utilizado para el manejo del melanoma de la región periocular, que incluyen desde la escisión quirúrgica hasta métodos destructivos como la crioterapia, radioterapia y tratamientos tópicos. La escisión quirúrgica tiene la ventaja de retirar los melanocitos alterados profundos, facilitando la detección del melanoma invasivo y permitiendo una evaluación histológica de los márgenes, disminuyendo el riesgo de recurrencia por la extracción incompleta de la lesión.

Objective: Describe the patient's clinical case of a melanoma diagnosis situated in the inferior eyelid of the right eye, compromising the tarsal conjunctiva and the lacrimal system. Th e patient was taken to a deferred Mohs micrographic surgery and eventually inferior eyelid reconstruction and intubation of the lachrymal system. Design: Case Report. A descriptive and retrospective study. Methodology: For the purpose of comparing the used surgical technique with other possible satisfactory methodologies, we conducted thorough research and analysis of literature referring to the pathological diagnosis and surgical treatment described. Description: A 69-year-old patient with a clinical case of 3 years of pigmented palpebral lesion compromising the eyelid and tarsal conjunctiva. The initial biopsy showed solar lentigo. Because of progressive growth and pigmentation, a second biopsy was performed, confirming the melanoma diagnosis compromising the inferior eyelid, palpebral border, inferior tarsal conjunctiva and punctum of the right eye. The patient was taken to a deferred Mohs micrographic surgery and palpebral reconstruction. Discussion: Melanoma is a malignant tumor developed from melanocyte degeneration. It is also the fi rst cause of death from malignant skin lesions and its incidence rate has been increasing signifi cantly over the last decade. There has been a variety of methods used to treat periocular melanoma including everything from surgical excision to destructive methods such as, cryotherapy, radiotherapy, and topical treatments. The surgical excision has the advantage of removing the deeply altered melanocytes, facilitating the detection of invasive melanoma and allowing histological evaluation of the margins, which diminishes the risk of reoccurrence from an incomplete extraction of the lesion.

Cilindros retrocorneanos: un hallazgo poco usual de la queratitis por sífilis / Retrocorneal cylinders: an unusual fi nding of syphilitic keratitis

Objetivo: Describir el caso de una paciente con una presentación inusual de queratitis intersticial por sífilis. Diseño: Estudio descriptivo, retrospectivo, reporte de caso. Metodología: Se realizó una revisión de la historia clínica del paciente y de la literatura con referencia al diagnóstico. Resultados: Paciente femenina de 67 años quien consulta por cuadro de 4 días de evolución de disminución progresiva y dolorosa de agudeza visual en ojo derecho. En el examen oftalmológico se evidenció una lesión cilíndrica, ramificada en cámara anterior, con adherencias al endotelio corneano, edema y leucoma corneano por lo cual se diagnosticó queratitis intersticial por sífilis; se confirmó por serología y se realizó el manejo correspondiente. Conclusiones: Aunque la queratitis intersticial por sífilis tiene baja incidencia y prevalencia en la actualidad, debe tenerse en cuenta dentro de los diagnósticos diferenciales en pacientes que presenten queratitis estromal no ulcerativa y así mismo, debe hacerse estudio serológico en todos los casos de queratitis estromal bilateral cuya causa no esté definida ya que puede ser la única manifestación de la enfermedad. Un hallazgo clínico raro es la aparición de cilindros, rollos o membranas retrocorneales. El conocimiento de todas las formas de presentación, aún las más infrecuentes, como en nuestro caso es importante en el diagnóstico y manejo de esta patología.

Objective: Describe the case of a patient with an unusual presentation of syphilitic interstitial keratitis. Design: A descriptive, retrospective study and case report. Methodology: A literature review was made about the pathology and specific diagnosis. Results: A 67-year-old female patient was seen for a 4-day course of progressive and painful decrease of visual acuity in the right eye. During the ophthalmologic examination, a cylindrical and branching lesion with adhesions to the corneal endothelium was noted, corneal edema and leukoma was also founded. Diagnosis of interstitial syphilitic keratitis was made; the clinical picture was confi rmed by serology and the patient was managed accordingly. Conclusions: Although syphilitic interstitial keratitis has low incidence and prevalence, this disease must be considered into the differential diagnosis of patients with non-ulcerative stromal keratitis and a serology study must be done in all cases of bilateral stromal keratitis, as it may be the only manifestation of the disease. An unusual finding is the appearance of cylinders, rolls or retrocorneal membranes. Knowledge of all forms of presentation, even the most infrequent, as in this case, is important in the diagnosis and management of this condition.

Pemetrexed in the treatment of relapsed/refractory primary central nervous system lymphoma.

BACKGROUND: Despite initial treatment with high-dose methotrexate-based regimens, many patients with primary central nervous system lymphoma (PCNSL) relapse and die from their disease. No standard of care exists at progression or relapse, but chemotherapy and in some cases radiation are usually used. Pemetrexed is a multitargeted antifolate, similar to methotrexate, but with a broader spectrum of activity. Because methotrexate is an integral part of PCSNL treatment, the authors assessed the antitumor activity and safety of pemetrexed in recurrent PCNSL. METHODS: Patients with relapsed/refractory PCNSL were enrolled in this trial. Treatment consisted of pemetrexed 900 mg/m(2) given every 3 weeks with low-dose dexamethasone, folate, and B12 supplementation. Each cycle was 6 weeks, and follow-up imaging was done before each new cycle. Treatment was continued until complete remission, progression, or toxicity. RESULTS: Eleven patients were treated, with a median age of 69.8 years and Karnofsky performance status of 70%; 10 of 11 patients had failed prior high-dose methotrexate. The median number of pemetrexed cycles given was 5, with an associated overall response rate of 55% and disease control rate of 91%. The 6-month progression-free survival (PFS) was 45%, median PFS was 5.7 months, and median overall survival was 10.1 months. Toxicities were primarily hematologic and infectious. CONCLUSIONS: Pemetrexed has single-agent activity in relapsed/refractory PCNSL. Toxicities were seen likely because of the higher than standard dose used. Further investigation of this agent or other multitargeted antifolates in PCNSL is warranted to determine optimal dose and efficacy in a more homogeneous population.

Inflamación idiopática de la órbita en la infancia / Idiopathic orbital inflammation in childhodd

Niño de dos años con inflamación idiopática de la órbita que ingresó por edema, rubor y calor en párpados izquierdos. Fue tratado con antibióticos de amplio espectro sin mejoría. Por empeoramiento del cuadro se llevó a cirugía para biopsia del tejido señalado en las imágenes diagnósticas. Por el aspecto macroscópico se inició una prueba terapéutica con corticoesteroides con excelente respuesta. El informe histopatológico reveló inflamación idiopática de la órbita que tiene múltiples diagnósticos diferenciales, los cuales requieren tratamientos diferentes. Se descartaron así otras patologías que pueden comprometer la vida del paciente...

Two-year old boy with idiopathic orbital inflammation admitted with left eyelids edema, redness and heat. He received broad-spectrum antibiotic therapy showing no improvement. He was taken to the operating room due to worsening of the condition´s status and an image guided biopsy of the tissues was conducted. Based on the macroscopic aspect, a therapeutic test with corticosteroids was initiated with an excellent response. The histopathology report revealed idiopathic orbital inflammation which has multiple differential diagnoses that require different treatments. Other potentially life-threatening conditions were out ruled this way...

Efecto supresivo de los ciclos cortos de glucocorticoides utilizados en asma sobre el eje hipotálamo-hipófisis-suprarrenal

Para aclarar el efecto supresivo que podrían tener los ciclos cortos de glucocorticoides sobre el eje hipotálamo-hipófisis-suprarrenal (H-H-S) se realizó un estudio prospectivo experimental, controlado, incluyendo en forma aleatoria 49 niños que consultaron al servicio de urgencias por presentar crisis asmática, y a quienes se les administró un ciclo corto de prednisolona a dosis de 1 mg/Kg/día durante 5 días. Se tomó una muestra para la medición del cortisol sérico inicial fue de 32 más o menos 24.2 microgr/dl, y el cortisol sérico posterior a la corticoterapia fue de 5.8 más o menos 3.3 microgr/dl. Aplicando la prueba t-student se encontró una diferencia significativa con p<0.0001. 35 pacientes (71.4 por ciento) tuvieron cortisol sérico bajo, lo que sugiere supresión del eje H-H-S. En tres pacientes (6.1 por ciento) se encontraron valores en el límite inferior normal. Los demás pacientes evidenciaron valores séricos normales. En conclusión, los ciclos cortos de glucocorticoides en niños pueden ocasionar supresión del eje H-H-S.