Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study.

BACKGROUND: Lurbinectedin, a selective inhibitor of oncogenic transcription, has shown preclinical antitumor activity against homologous recombination repair-deficient models and preliminary clinical activity in BRCA1/2 breast cancer. PATIENTS AND METHODS: This phase II basket multitumor trial (NCT02454972) evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 21 patients with pretreated germline BRCA1/2 breast cancer. Patients with any hormone receptor and human epidermal growth factor receptor 2 status were enrolled. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Confirmed partial response (PR) was observed in six patients [ORR = 28.6%; 95% confidence interval (CI) 11.3% to 52.2%] who had received a median of two prior advanced chemotherapy lines. Lurbinectedin was active in both BRCA mutations: four PRs in 11 patients (36.4%) with BRCA2 and two PRs in 10 patients (20.0%) with BRCA1. Median DoR was 8.6 months, median PFS was 4.1 months and median OS was 16.1 months. Stable disease (SD) was observed in 10 patients (47.6%), including 3 with unconfirmed response in a subsequent tumor assessment [ORR unconfirmed = 42.9% (95% CI 21.8% to 66.0%)]. Clinical benefit rate (PR + SD ≥ 4 months) was 76.2% (95% CI 52.8% to 91.8%). No objective response was observed among patients who had received prior poly (ADP-ribose) polymerase inhibitors. The most common treatment-related adverse events (AEs) were nausea (61.9%), fatigue (38.1%) and vomiting (23.8%). These AEs were mostly grade 1/2. The most common grade 3/4 toxicity was neutropenia (42.9%: grade 4, 23.8%: with no febrile neutropenia). CONCLUSIONS: This phase II study met its primary endpoint and showed activity of lurbinectedin in germline BRCA1/2 breast cancer. Lurbinectedin showed a predictable and manageable safety profile. Considering the exploratory aim of this trial as well as previous results in other phase II studies, further development of lurbinectedin in this indication is warranted.

A phase II trial of erlotinib as maintenance treatment after concurrent chemoradiotherapy in stage III non-small-cell lung cancer (NSCLC): a Galician Lung Cancer Group (GGCP) study.

PURPOSE: This single arm, phase II study aims to evaluate the role of epidermal growth factor receptor-tyrosine-kinase inhibitor erlotinib as maintenance therapy following concurrent chemoradiotherapy (cCRT) in unresectable locally advanced non-small-cell lung cancer (NSCLC). METHODS: Patients with unresectable stage IIIA o dry IIIB NSCLC with no evidence of tumor progression after receiving a standard cCRT regimen with curative intent were included. Oral erlotinib 150 mg/day was administered within 4-6 weeks after the end of the cCRT for a maximum of 6 months if no disease progression or intolerable toxicity occurred. Primary end point was the progression-free rate (PFR) at 6 months. Secondary end points included time to progression (TTP) and overall survival (OS). RESULTS: Sixty-six patients were enrolled and received maintenance treatment with erlotinib [average: 4.5 months (95 % CI 4.0-5.0)]. PFR at 6 months was 63.5 % (41/66). With a median follow-up of 22.7 months (95 % CI 13.5-37.1), the median TTP was 9.9 months (95 % CI 6.2-12.1), and the median OS was 24.0 months (95 % CI 17.3-48.6). Most common adverse events (AEs) related to erlotinib were rash (78.8 %; 16.7 % grade 3), diarrhea (28.8 %; 1.5 % grade 3), fatigue (15.2 %; 1.5 % grade 3), anorexia (7.6 %; 1.5 % grade 3) and vomiting (4.6 %; none grade 3). Five patients (7.6 %) were withdrawn due to AEs. CONCLUSIONS: Erlotinib as maintenance therapy is an active treatment after cCRT in unselected patients with stage III NSCLC, reaching a 6-month PFR of 63.5 % and a median OS of 24 months. The safety profile of maintenance erlotinib was as expected and manageable.

Grosor corneal en una muestra de adultos de la población chilena / Corneal thickness in a sample of adults of the chilean population

The central corneal thickness (CCT) is crucial to the estimation of the intraocular pressure (IOP). There are variations among different populations. The objective of the present job was to determine de CCT in a sample of Chilean population. The sample was taken at random from patients attending the office of an ophthalmologist of the Clinical Hospital of the University of Chile. The patients age ranged between 15 and 65 years. We discarded patients with IOP over 21 mm Hg, Spherical Equivalent greater than 6 diopters or with ophthalmological local treatment. The CCT was measured using ulotrasonographyc pachymeter. We enrolled 127 patients and analized 253 eyes. The CCT average was 537,70 μm 39.34 um with an standard deviation of 32.09 um. The CCT of the studied population was less than the reported in Spanish populations in USA, greater Japanese and Afro-Americans and less than Europeans and Chinese. It is important to consider the ethnic variation of the CCT in our population regarding its effect in the correction of the IO.

A phase II randomized trial of gemcitabine-docetaxel versus gemcitabine-cisplatin in patients with advanced non-small cell lung carcinoma.

PURPOSE: To test efficacy and tolerability of non-platinum regimens for advanced non-small-cell lung cancer (NSCLC). METHODS: Chemonaive patients with measurable stage IIIB/IV NSCLC treated with gemcitabine and cisplatin (GC), or gemcitabine and docetaxel (GD), maximumsix cycles in a phase IIB trial. RESULTS: A total of 108 patients were randomized. Response rates (GC vs. GD, respectively): complete 3.6/2.0%, Partial 30.9/38.0%. Median Overall Survival (OS): 8.9 months in both groups (P = 0.53); and median time to progression (TTP): 6.2/5.5 months respectively (P = 0.61). Toxicities included (GC vs. GD, respectively): grade 3-4 neutropenia 49.1/41.2%; grade 3 thrombocytopenia 30.9/3.9%; grade 3 anemia 14.5/3.9%. Non-haematological toxicity was similar, except for nausea and vomiting, (16.3/2%); renal toxicity (3.7/0%) and hepatic toxicity (5.6/12.7%). CONCLUSIONS: With a higher overall response rate and lower toxicity, GD is a good first treatment option for advanced NSCLC.

Significados asociados a la actividad delictiva en hombres que se encuentran privados de libertad, en Centro de Detención Preventiva Santiago Sur / Meanings associated to criminal activities in men who are deprived of their liberty, in Centro de Detencion Preventiva Santiago Sur

El presente estudio pretende comprender los significados que las personas transgresoras de ley, le otorgan a su propia actividad delictiva, específicamente al robo, mediante la identificación y relación de los temas emergentes durante este estudio, con constructos teóricos. La identificación y comprensión de estos temas, se realiza en torno a una visión general de Terapia Ocupacional. Para abordar esta investigación, de carácter cualitativo, se contextualiza el tema a estudiar en Centro de Detención Preventiva Santiago Sur, siendo los participantes hombres entre 27 y 35 años, que cumplen condena por delito de robo. La información recopilada, se extrae a partir de cinco entrevistas semi estructuradas, para ser luego analizadas a través de la Teoría Fundada, que permite revisar los fenómenos emergentes y ponerlos en discusión con los planteamientos teóricos. Los hallazgos obtenidos, señalan que los significados asociados al robo, se pueden relacionar a distintos fenómenos como; factores psicosociales de riesgo, inicio delictual e influencia y pertenencia a redes sociales, conducta exploratoria, procesos psicosociales, interacción simbólica y mapa significativo propio, identidad personal, acción preconcebida y motivaciones del robo, autoconcepto y autoeficacia.

The following Seminar is orientated to understand the meanings that people outside the law give to their own criminal activities, primarily stealing, through the identification and connection between the emerging issues and the theoretical constructs made through this study. The identification and understanding of this topic is developed focusing on Occupational Therapy general views. To develop this qualitative research, the project takes place in Centro de Detención Preventiva ( Preventive detention center) Santiago Sur, Chile, with men between the ages of 27 and 35 years old, which are convicted for robbery. The information was collected from five semi-structured interviews, and analyzed with the Grounded Theory. This allows the review of emerging phenomena and compares them with the theoretical approach. The results indicate that the meanings related to stealing are correlated with different phenomena, like: psychosocial risk factors, criminal initiation and the influence of being part of social networks, exploratory behavior, psychosocial development, symbolic interaction and meaningful map, personal identity, premeditated action and motivation for stealing, self-concept and self-efficiency. After discovering and understanding the phenomena from the participant’s point of view, it is clear to see two different ways for understanding the act of stealing, which differ from the meaning that the person gives to the act. On one hand, they see themselves as thieves and participate with the role. And on the other, they do not see themselves as thieves, they find an identity with the job, becoming the main activity in their lives. The analysis and results of the meanings associated to the act of robbery can be interesting for Occupational Therapy. This research includes key elements for this discipline and its development, including the motivation and personal subjectivity, bounds, relationships and the context for their development, making all together the...

[Histiocytic necrotizing lymphadenitis: report of three cases]. / Tumor cervical por enfermedad de Kikuchi: Una entidad clínica a la que no estamos habituados. Caso clínico.

Histiocytic necrotizing lymphadenitis (HNL), also known as Kikuchi 5 disease is a rare condition of unknown etiology. Patients present with cervical lymph node enlargement, fever and malaise. The diagnosis is made by excision biopsy. However, this entity must be distinguished from both reactive processes and malignant tumors such as lymphoma. The clinical course is self limited with spontaneous resolution within a few months. We report three patients with the disease. A 37 year-old woman with a 4 months history of a painless submaxillary mass of 2.5 cm diameter, attached to the deep tissues of the neck. The mass was excised and the biopsy report was HNL. After 26 months of follow up, the patient is asymptomatic. A 30 year-old woman with a history of 2 months of a painless lateral cervical mass and aspiration biopsy was reported as suspicious for lymphoma. An excision biopsy was performed, that was reported as HNL. In both patients, lymphoma was ruled out by immunohistochemistry. A 33 year-old woman with a 3 weeks history of an asymptomatic lateral cervical mass. Biopsy was reported as HNL. This condition must be included in the differential diagnosis of cervical asymptomatic masses. The clinician must be aware of it to avoid long-term, costly treatments.

Tumor cervical por enfermedad de Kikuchi: Una entidad clínica a la que no estamos habituados. Caso clínico / Histiocytic necrotizing lymphadenitis: Report of three cases

Histiocytic necrotizing lymphadenitis (HNL), also known as Kikuchi 5 disease is a rare condition of unknown etiology. Patients present with cervical lymph node enlargement, fever and malaise. The diagnosis is made by excision biopsy. However, this entity must be distinguished from both reactive processes and malignant tumors such as lymphoma. The clinical course is self limited with spontaneous resolution within a few months. We report three patients with the disease. A 37 year-old woman with a 4 months history of a painless submaxillary mass of 2.5 cm diameter, attached to the deep tissues of the neck. The mass was excised and the biopsy report was HNL. After 26 months of follow up, the patient is asymptomatic. A 30 year-old woman with a history of 2 months of a painless lateral cervical mass and aspiration biopsy was reported as suspicious for lymphoma. An excision biopsy was performed, that was reported as HNL. In both patients, lymphoma was ruled out by immunohistochemistry. A 33 year-old woman with a 3 weeks history of an asymptomatic lateral cervical mass. Biopsy was reported as HNL. This condition must be included in the differential diagnosis of cervical asymptomatic masses. The clinician must be aware of it to avoid long-term, costly treatments.

Docetaxel-induced interstitial pneumonitis following non-small-cell lung cancer treatment.

Interstitial pneumonitis has been described infrequently following administration of docetaxel, used alone or in combination with other chemotherapeutic agents or concurrent irradiation, for non-small-cell lung cancer (NSCLC). This toxicity is of special relevance in NSCLC, as clinical severity and differential diagnosis may be especially challenging. It seems to be due to type I and type IV hypersensitivity reactions to the drug. Clinical and radiographic features are nonspecific and diagnosis is made by exclusion. The rate of grade III-IV docetaxel-induced pneumonitis, ranging from 7 to 47%, depends on several factors, including total dose, chemotherapy schedule and especially concomitant docetaxel treatment with gemcitabine and radiotherapy. Although the usual outcome is cure, it sometimes eventually progresses to pulmonary fibrosis despite steroid treatment. This toxicity must be taken into account when planning treatment strategies for NSCLC in order to reduce its rate and to achieve prompt diagnosis and treatment.

[Incidence of hypocalcemia after total thyroidectomy]. / Incidencia de hipocalcemia pos tiroidectomía total.

BACKGROUND: Postoperative hypocalcemia is one of the most common complications of thyroid surgery. It is related to the type of disease (malignant or benign), the number of identified parathyroid glands during the surgical procedure, and the surgeon's experience. Total thyroidectomy is the procedure of choice in our hospital for benign and malignant thyroid disease, but it can increase the incidence of complications. AIM: To evaluate the incidence of postoperative hypocalcemia in patients subjected to a total thyroidectomy. MATERIAL AND METHODS: Two studies were performed. A retrospective review of medical records of 448 patients subjected to total thyroidectomy, looking for serum calcium levels of less than 8 mg/dl and clinical signs of hypocalcemia. In a second study, 45 patients were followed with measurements of preoperative and postoperative serum calcium levels. RESULTS: In the retrospective study, only 136 records had reliable information. Clinical signs of hypocalcemia were registered in 14% of patients and a low serum calcium level was detected in 50%. In the prospective study, 42% of patients had a postoperative low serum calcium level and seven patients (15%) had symptoms. Patients were handled with oral calcium and calcitriol in some cases. Ninety nine percent of patients had normal serum calcium levels two moths after surgery. CONCLUSIONS: In this series, the rate of postoperative hypocalcemia after total thyroidectomy is similar to international reports.

Incidencia de hipocalcemia pos tiroidectomía total / Incidence of hypocalcemia after total thyroidectomy

Background: Postoperative hypocalcemia is one of the most common complications of thyroid surgery. It is related to the type of disease (malignant or benign), the number of identified parathyroid glands during the surgical procedure, and the surgeon's experience. Total thyroidectomy is the procedure of choice in our hospital for benign and malignant thyroid disease, but it can increase the incidence of complications. Aim: To evaluate the incidence of postoperative hypocalcemia in patients subjected to a total thyroidectomy. Material and methods: Two studies were performed. A retrospective review of medical records of 448 patients subjected to total thyroidectomy, looking for serum calcium levels of less than 8 mg/dl and clinical signs of hypocalcemia. In a second study, 45 patients were followed with measurements of preoperative and postoperative serum calcium levels. Results: In the retrospective study, only 136 records had reliable information. Clinical signs of hypocalcemia were registered in 14 percent of patients and a low serum calcium level was detected in 50 percent. In the prospective study, 42 percent of patients had a postoperative low serum calcium level and seven patients (15 percent) had symptoms. Patients were handled with oral calcium and calcitriol in some cases. Ninety nine percent of patients had normal serum calcium levels two moths after surgery. Conclusions: In this series, the rate of postoperative hypocalcemia after total thyroidectomy is similar to internaitonal reports.

Utilidad clínica del estudio de diseminación inicial en cáncer de mama estadios I y II / Clinical utility of initial dissemination study an patients with stage I or II breast cancer I

Se evalúa el rendimiento y utilidad clínica del estudio inicial de diseminación en nuestra serie de 616 casos de cáncer de mama, centrado especialmente en los estados I y II ( 374 casos ), buscando establecer si existe un subgrupo de mayor riesgo en el cual esté justificado el estudio inicial de diseminación. Se separaron las pacientes en 2 grupos de acuerdo a la palpación de ganglios axilares: sospechosos de metástasis (N1), no sospechosos (N0); comprobando que las pacientes N1 tenían un 5,99 por ciento de metástasis iniciales (13/217) versus un 2,3 por ciento (4/174) en las pacientes N0, (p=0,085); sin embargo durante el seguimiento de la serie (23 años) se comprobó que un porcentaje mayor de pacientes N1 desarrolló metástasis (50/ 204=24,5 por ciento) en relación a las pacientes N0 (25/170=14,7 por ciento) (p=0,0198); aunque no en todos estos casos los estudios iniciales fueron útiles para diagnosticar metástasis. En las pacientes que desarrollaron metástasis durante el seguimiento, los estudios iniciales de diseminación negativos, sirvieron de base comparativa a los estudios posteriores que mostraron metástasis, obteniéndose una utilidad clínica global para dichos estudios de un 24,4 por ciento (53/217) en las pacientes N1 versus un 14,4 por ciento (25/174) en las pacientes N0 (p=0,0154). En el 21 por ciento de las pacientes estado III, el estudio inicial de diseminación demostró metástasis. En 41 de 204 pacientes N1 (20 por ciento) la ecotomografía abdominal demostró colelitiasis, lo que se consideró un beneficio adicional del examen. Se concluye que el estudio inicial de diseminación es de utilidad clínica en pacientes con ganglios axilares palpables.

Gemcitabine, cisplatin and vinorelbine as induction chemotherapy followed by radical therapy in stage III non-small-cell lung cancer: a multicentre study of galician-lung-cancer-group.

PURPOSE: To determine the effectiveness of a gemcitabine-cisplatin-vinorelbine combination in patients with stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients (n=46) with stage III NSCLC and naive of therapy were recruited into the trial to receive gemcitabine (G, 1000 mg/m(2)) on days 1 and 8, cisplatin (C, 100 mg/m(2)) on day 1 and vinorelbine (V, 25 mg/m(2)) on days 1 and 8 every 21 days for three cycles. RESULTS: Two patients achieved complete response (CR) and 23 partial response (PR), overall response 52%. Subsequent radical surgery included nine patients of whom four were non-resectable and five were resected and with 1 CR. Radiotherapy was administered to 31 patients, and two achieved CR. The median time to progression and overall survival were 37 and 50 weeks, respectively. Grade 3-4 neutropenia and thrombocytopenia occurred in 35% of cycles, with two toxic deaths. Severe non-haematological toxicity was uncommon. CONCLUSIONS: This GCV combination is effective in patients with stage III NSCLC, and with an acceptable toxicity.

Phase II study of weekly irinotecan (CPT-11) as second-line treatment of patients with advanced colorectal cancer.

This phase II trial studied the antitumor effect and toxicity of weekly irinotecan (CPT-11, 125 mg/m(2) 60 min iv infusion, weekly for 4 wk plus 2 wk rest) as second-line chemotherapy in patients with advanced colorectal cancer (CRC) resistant or refractory to prior 5-fluorouracil (5-FU) therapy. Sixty-nine patients with adenocarcinoma (57% in the colon and 43% in the rectum) were enrolled. The median number of treatment cycles received per patient was 4 (range, 1-6). Overall response rate was 18% (95% CI, 9-26), with 4 complete responses (6%) and 8 partial responses (12%), and a median duration of response of 8.1 mo (95% CI, 4.2-12.1). Stable disease was observed in 19 patients (28%). The median time to disease progression was 5.2 mo (95% CI, 4.3-6.1), and the median overall survival was 13.3 mo (95% CI, 9.8-16.8 months). The toxicity profile was favorable: grade 3/4 delayed diarrhea was observed in 10 patients (14.5%) in one cycle each, and grade 3/4 neutropenia in 6 patients (8.7%) and 6 cycles (3.3%). No febrile neutropenia or infection was documented. Grade 3/4 nausea and vomiting were reported in 1 (1.4%) and 7 patients (10.1%), respectively. In conclusion, this phase II trial showed a response rate and a toxicity profile of weekly CPT-11 in line with the results of prior phase II studies.

Mediastinal non-seminomatous germ cell tumours (MNSGCT) treated with cisplatin-based combination chemotherapy.

BACKGROUND: Primary mediastinal non-seminomatous germ cell tumours (MNSGCT) constitute a rare malignancy. This study was performed to review our experience with cisplatin-based chemotherapy in patients with MNSGCT. PATIENTS AND METHODS: Patients with MNSGCT treated with cisplatin-based combination chemotherapy between 1978-1995 in three university hospitals in Spain were retrospectively studied. RESULTS: There were 25 males and two females with a median age of 26 years (range 4-71). Fifteen patients had disease confined to the mediastinum and 12 had metastatic disease. All patients were treated with cisplatin chemotherapy regimens (PVB: 7, BEP: 6, and other regimens 12) and considered for residual mass surgery (RMS) when indicated. Eleven patients (40.7%) were rendered disease-free with initial treatment: four with chemotherapy alone, one with surgery plus adjuvant chemotherapy and six with chemotherapy plus RMS. Three of these patients relapsed at two, six and seven months. The remaining 16 had unfavourable responses (five partial response, three no change, seven progressive disease and one toxic death). Eleven patients received salvage treatment but none of them achieved a durable response. After a median follow-up of 77 months (range 1-168), 10 patients remain alive. Actuarial survival at five years is 31.7%. No patients in this series developed a haematological malignancy. Chromosomal analysis showed that 2 out of 10 patients (20%) had a 47XXY karyotype. CONCLUSIONS: Only patients who achieved disease-free status are likely to be cured. Therefore, new up-front strategies are needed for the treatment of MNSGCT.

Acute tumor lysis syndrome complicating conditioning therapy for bone marrow transplantation in a patient with chronic lymphocytic leukemia.

We report a case of acute tumor lysis syndrome appearing during chemoradiotherapeutic conditioning for allogeneic bone marrow transplantation (BMT) in a patient with chronic lymphocytic leukemia. This complication appeared in spite of prophylactic therapy and although the outcome was satisfactory, the patient required temporary hemodialysis and strict supportive care. This case emphasizes the importance of recognizing that the acute tumor lysis syndrome is not confined to high-grade malignancies.