Phase I study of peposertib and avelumab with or without palliative radiotherapy in patients with advanced solid tumors.

INTRODUCTION: We report results from a phase I, three-part, dose-escalation study of peposertib, a DNA-dependent protein kinase inhibitor, in combination with avelumab, an immune checkpoint inhibitor, with or without radiotherapy in patients with advanced solid tumors. MATERIALS AND METHODS: Peposertib 100-400 mg twice daily (b.i.d.) or 100-250 mg once daily (q.d.) was administered in combination with avelumab 800 mg every 2 weeks in Part A or avelumab plus radiotherapy (3 Gy/fraction × 10 days) in Part B. Part FE assessed the effect of food on the pharmacokinetics of peposertib plus avelumab. The primary endpoint in Parts A and B was dose-limiting toxicity (DLT). Secondary endpoints were safety, best overall response per RECIST version 1.1, and pharmacokinetics. The recommended phase II dose (RP2D) and maximum tolerated dose (MTD) were determined in Parts A and B. RESULTS: In Part A, peposertib doses administered were 100 mg (n = 4), 200 mg (n = 11), 250 mg (n = 4), 300 mg (n = 6), and 400 mg (n = 4) b.i.d. Of DLT-evaluable patients, one each had DLT at the 250-mg and 300-mg dose levels and three had DLT at the 400-mg b.i.d. dose level. In Part B, peposertib doses administered were 100 mg (n = 3), 150 mg (n = 3), 200 mg (n = 4), and 250 mg (n = 9) q.d.; no DLT was reported in evaluable patients. Peposertib 200 mg b.i.d. plus avelumab and peposertib 250 mg q.d. plus avelumab and radiotherapy were declared as the RP2D/MTD. No objective responses were observed in Part A or B; one patient had a partial response in Part FE. Peposertib exposure was generally dose proportional. CONCLUSIONS: Peposertib doses up to 200 mg b.i.d. in combination with avelumab and up to 250 mg q.d. in combination with avelumab and radiotherapy were tolerable in patients with advanced solid tumors; however, antitumor activity was limited. GOV IDENTIFIER: NCT03724890.

[Cervical necrotizing cellulitis caused by spider bite]. / Celulitis necrosante cervical por picadura de arácnido.

Foremost causes of originating shallow painful inflammations on the neck are: boils, carbuncle or infected dermoid cysts and atheroma. When remembering other possible inflammatory sources in this site we cont with insects bites through scarces in our environment. We report one case of spider's bite (Loxoceles rufecens) originating a necrotic neck cellulitis and remind also the several clinical symptoms of arachnid bites scarce in our environment.

[Retroauricular approach to complete obliteration of the external ear canal caused by osteoid osteoma]. / Abordaje retroauricular en la obliteración completa del conducto auditivo externo por un osteoma osteoide.

Osteoid osteoma of the temporal bone is an infrequent benign bone tumor. The suspected diagnosis is based on clinical findings (occasionally pain, cosmetic deformities, repeated external otitis and conductive hearing loss), otoscopy, the radionuclide bone scan, and computerized tomography. Histopathology confirms the diagnosis of osteoma. Pain responds to acetylsalicyclic acid. Treatment is surgical excision by curettage and eburnation of the bone margins using an endaurul approach. We report a complete obliteration of the outer ear canal by an osteoid osteoma in a 32-year-old patient. A postauricular approach was required because of the large size of the tumor.

[Results of treating cervical metastases of an unknown primary tumor. A report of 29 cases]. / Resultados del tratamiento de las metástasis cervicales de primario no filiado. A propósito de 29 casos.

A retrospective study was made of 29 patients with cervical metastasis of an unknown primary tumor. Sixteen patients received local treatment with surgery and radiotherapy (group A) and 13 patients were treated with induction chemotherapy, surgery and radiotherapy (group B). All patients responded. Local recurrence occurred in 21.4% of group A and 20% of group B. The frequency of distant metastases was similar (18.8% vs 15.4%). The mean survival time of 68 months in group A was longer than the 40 months of group B, and the a 2-year survival rate was 81% in group A and 67% in group B. The 5-year survival was better in group B (56% vs 40%). The primary tumor was identified twice as often in the patients who received only local treatment (group A 37.5% and group B 15.4%). Detection of the primary tumor was the only factor that significantly influenced patient survival.

[Postoperative complication in stapedectomy: excessive introduction of the prothesis in the oval window]. / Complicación postoperatoria en la estapedectomía: excesiva introducción de la prótesis en la ventana oval.

Postoperative failures and complications detected in patients who undergo surgery for otosclerotic disease are not uncommon in stapes surgery. Prosthesis displacement and incus necrosis are the most common findings in review stapedectomy. We report the case of a patient who had tinnitus, vertigo, and non-recovery of air conduction thresholds without neurosensorial lesions after stapes surgery. The suspected diagnosis of excessive introduction of the prosthesis in the oval window was confirmed by computed tomography, which showed the radio-opaque image of the McGee metal prosthesis. The prosthesis replacement and literature review are discussed.

[Evaluation of informed consent in ear, nose, and throat practice]. / Valoración del consentimiento informado en ORL.

The patient has a right to information about his or her disease and therapeutic options. A retrospective study was made of the opinion that 40 patients who underwent ear, nose and throat surgery had of this information. After receiving verbal and written information, they completed a questionnaire. Only 1 patient (2.9%) wanted no information, 100% wanted information about the evolution of the disease without treatment, 20.6% were more alarmed after receiving information, and 41.1% thought that written information was essential.

[Bilateral recurrent nerve paralysis secondary to Ludwig's angina]. / Parálisis recurrencial bilateral secundaria a angina de Ludwig.

Although the incidence of Ludwig's angina has diminished, it still occurs. This disease can have life-threatening complications, including deep neck infection and mediastinitis. We report a case of Ludwig's angina with bilateral vocal cord paralysis secondary to cervical spread of infection.

[Radiotherapy alone versus neo-adjuvant chemotherapy and irradiation in the treatment of carcinoma of the cavum]. / Radioterapia exclusiva frente a quimioterapia neoadyuvante más radioterapia en el tratamiento de los carcinomas de cávum.

Radiation therapy is the usual treatment for nasopharyngeal carcinoma. However, in recent years the use of neoadyuvant chemotherapy in the treatment of local and regionally advanced carcinoma has been investigated. We report the results of a retrospective study of two treatments used in our center. The study included 68 patients: 34 (group A) who received radiotherapy alone and 34 (group B) who received neoadyuvant chemotherapy before radiotherapy. In group A, 70.6% achieved a complete clinical response: 23.5% relapsed: 5 patients presented distant metastases. Survival rates at 5 and 10 years were 53% and 27% respectively; the disease-free survival was 71.4% at 5 years and 54% at 10 years. In group B, the complete clinical response rate to neoadyuvant chemotherapy was 35.3%, which increased to 73.5% when the treatment was complemented with radiotherapy. The relapse rate was 14.7%; the survival rates at 5 and 10 years were 49.5% and 49%, respectively; and the disease-free survival was 77.2% at 5 and 10 years.

[Primary health care in otorhinolaryngology. Descriptive study]. / Asistencia primaria en otorrinolaringología. Estudio descriptivo.

We present a one-year study describing the ENT pathology seen in a rural ENT clinic. The study included 1,516 patients whose characteristics are described (age, sex, diagnosis, and others).

[Nasal septum cyst of odontogenic origin]. / Quiste en septum nasal de origen odontógeno.

Cysts in the nasal septum are unusual, and the presence of a dental cyst is even rarer. A cyst of dental origin was produced by dental root fracture in the nasal septum. The differential diagnosis and management are discussed.

[Metastasis of breast carcinoma in parotid. A case report and review of the literature]. / Metástasis de carcinoma de mama en parótida: a propósito de un caso y revisión de la bibliografía.

Breast cancer is a systemic illness that sometimes affects the ENT area. We report a case of parotid tumor with progressive growth, which rarely originals in the ENT area. We review the literature and discuss the treatment.

Cardiotocografía en las pacientes de alto riesgo obstétrico: comparación de los monitores ante e intraparto / m

Se estudian 100 pacietnes de alto riesgo obstétrico a quienes se les realiza monitoreo anteparto seriado sin test de sobrecarga, y comparamos aquéllos que precedían a la semana del parto, con controles intraparto registrados con el electrodo interno de forma espiral de Hon. Se observa la frecuente aparición de registros posiblemente normales y anormales en estos casos, así también encontramos que entre los registros anteparto normales presentaron el 35 por ciento alteraciones de la frecuencia cardíaca fetal durante el trabajo de parto y a medida que se incrementa la frecuencia de la gravedad de los hallazgos precoces, mucho más frecuente es la presencia de alteración de la frecuencia cardíaca fetal intraparto. Hallamos además, que en todos los tipos de registro la desaceleración más frecuente fue la variable y que la incidencia de meconio en estos casos durante el trabajo de parto fue de 50 por ciento