Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): a phase IIIb trial.

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is the standard of care for some patients with advanced ovarian cancer. We evaluated the efficacy and safety of PARP inhibitor rechallenge. PATIENTS AND METHODS: This randomized, double-blind, multicenter trial (NCT03106987) enrolled patients with platinum-sensitive relapsed ovarian cancer who had received one prior PARP inhibitor therapy for ≥18 and ≥12 months in the BRCA-mutated and non-BRCA-mutated cohorts, respectively, following first-line chemotherapy or for ≥12 and ≥6 months, respectively, following a second or subsequent line of chemotherapy. Patients were in response following their last platinum-based chemotherapy regimen and were randomized 2 : 1 to maintenance olaparib tablets 300 mg twice daily or placebo. Investigator-assessed progression-free survival (PFS) was the primary endpoint. RESULTS: Seventy four patients in the BRCA-mutated cohort were randomized to olaparib and 38 to placebo, and 72 patients in the non-BRCA-mutated cohort were randomized to olaparib and 36 to placebo; >85% of patients in both cohorts had received ≥3 prior lines of chemotherapy. In the BRCA-mutated cohort, the median PFS was 4.3 months with olaparib versus 2.8 months with placebo [hazard ratio (HR) 0.57; 95% confidence interval (CI) 0.37-0.87; P = 0.022]; 1-year PFS rates were 19% versus 0% (Kaplan-Meier estimates). In the non-BRCA-mutated cohort, median PFS was 5.3 months for olaparib versus 2.8 months for placebo (HR 0.43; 95% CI 0.26-0.71; P = 0.0023); 1-year PFS rates were 14% versus 0% (Kaplan-Meier estimates). No new safety signals were identified with olaparib rechallenge. CONCLUSIONS: In ovarian cancer patients previously treated with one prior PARP inhibitor and at least two lines of platinum-based chemotherapy, maintenance olaparib rechallenge provided a statistically significant, albeit modest, PFS improvement over placebo in both the BRCA-mutated and non-BRCA-mutated cohorts, with a proportion of patients in the maintenance olaparib rechallenge arm of both cohorts remaining progression free at 1 year.

INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line.

BACKGROUND: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). METHODS: Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). RESULTS: The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP). CONCLUSIONS: This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01379989.

Holmes-Adie syndrome as an early manifestation of systemic lupus erythematosus. / Síndrome de Holmes-Adie como primera manifestación de lupus eritematoso sistémico.

Lupus is an autoimmune disease with multiple manifestations and multiorgan damage. Neuro-ophthalmic disorders are the less common ophthalmological manifestations of lupus. Adie's tonic pupil is mostly idiopathic and may rarely be caused by autoimmune disorders. The combination of abnormal pupil size and a decrease or loss of deep tendon reflexes is usually called Holmes-Adie syndrome. A case is reported of Holmes-Adie syndrome as an early manifestation of systemic lupus erythematosus.

Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease. / Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert.

BACKGROUND AND OBJECTIVES: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1. MATERIAL AND METHODS: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide. RECOMMENDATIONS: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives. CONCLUSION: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up.

Usefulness of omalizumab in rapid drug desensitization in patients with severe anaphylaxis induced by carboplatin: open questions

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Safe and successful protocol for desensitization to abiraterone

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Allergic reaction to undeclared lupin in a chocolate

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Pseudomyxoma peritonei treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: results from a single centre

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare, slowly progressive disease whose prognosis depends primarily on the completeness of cytoreduction. The value of intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and of additional factors predicting long-term outcome and disease-free survival (DFS) remains poorly understood. This study aims to analyse survival rates and prognostic factors in patients undergoing maximal cytoreduction and HIPEC. METHODS: Thirty patients were selected from a prospective database of records for patients undergoing cytoreduction and HIPEC with mitomycin C or paclitaxel. Overall survival (OS), DFS, and the prognostic factors influencing them, were examined using multivariate analysis. RESULTS: Median follow-up was 44 months (range, 8-144). Histological classification of PMPs was DPAM in 6/30 of cases, PMCA-I in 10/30 and PMCA in 14/30. Complete cytoreduction (CC-0 and CC-1) was achieved in 28/30 of patients and CC-2 in 2/30. Median OS was 111 months (range 0-230) and five-year OS rate was 67%. Median DFS was 53.5 months (range 0-120) and 5-year DFS rate was 44%. Incomplete cytoreduction, lymph node involvement and PCI>20 were associated with poor prognosis for OS, while lymph node involvement, elevated CA-125 levels, unfavourable histology and previous chemotherapy were associated with poor outcomes for DFS. There was morbidity of Grade 3 or higher in 9/30. Post-operative mortality occurred in 1 case. CONCLUSION: Cytoreduction plus peritonectomy procedures combined with HIPEC is a safe treatment and could improve survival rates. Since the optimal cytoreduction is the primary prognostic factor, patients should be centralised under the care of experienced teams (AU)

[Recurrent signet-ring cell gastric carcinoma evidenced by FDG-PET]. / Recurrencia de un carcinoma gástrico de células en anillo de sello demostrada por PET-FDG.

OBJECTIVE: To present the case report of a patient with undifferentiated and diffuse signet-ring cell gastric carcinoma in which FDG-PET evidenced recurrent disease. MATERIALS AND METHODS: The patient was diagnosed of a stage III gastric carcinoma in 1994 and was treated with a subtotal gastrectomy. In February 2003, recurrent disease was detected in mediastinal and left supraclavicular lymph nodes. The patient was treated with chemotherapy and radiotherapy, reaching a complete response. After 6 months free of disease, he presented an elevation of the tumor markers with negative results in conventional imaging methods (upper digestive endoscopy, bone scintigraphy, and CT). An FDG-PET scan was performed to rule out recurrent disease. RESULTS: FDG-PET detected pathologic findings suggestive of malignant disease in right supraclavicular and mediastinal lymph nodes. These findings were confirmed by clinical follow-up and with another CT scan performed 4 months later. CONCLUSIONS: In this case report we stress the importance of early recurrence by FDG-PET in a non-intestinal gastric carcinoma. This is of interest given the greater difficulty to detect mucous secreting and/or producing carcinomas with the PET-FDG.

[Alcohol consumption in schoolchildren: motivations and attitudes]. / Consumo de alcohol en escolares: motivaciones y actitudes.

OBJECTIVE: To determine the levels of alcohol consumption among 8th grade (EGB) students in Cuenca, including the predisposing circumstances and factors as well as the children's motivation and attitudes. DESIGN: Descriptive observation study of a cross-sectional [correction of crossover] design. SETTING: Primary Care: the school population of the city of Cuenca. PATIENTS AND OTHER PARTICIPANTS: 672 school-children of both sexes in 8th grade (EGB). MEASUREMENTS AND MAIN RESULTS: An anonymous questionnaire with 30 closed questions was administered. 60% of the school-children had consumed alcohol on some occasion. In 54.94% of cases, friends first invited them to drink alcohol; in 33.59%, a family member. 1.4% of the children admitted to drinking alcohol daily (2.1% of boys against 0.7% of girls). 57.3% of fathers, 24.3% of mothers, 25.8% of brothers and 38% of friends consumed alcohol habitually. 36.9% of the children did not think that alcohol was a drug. CONCLUSIONS: The levels of alcohol consumption in the section of the population studied were high. Children began early and had easy access to alcoholic drinks. The level of consumption in their family and social environment was very high and was related to children's consumption. These results highlight the need for a preventive programme.