Rucaparib in recurrent ovarian cancer: real-world experience from the rucaparib early access programme in Spain - A GEICO study.

BACKGROUND: Rucaparib is a poly(ADP-ribose) polymerase inhibitor approved in Europe as maintenance therapy for recurrent platinum-sensitive (Pt-S) ovarian cancer (OC). The Rucaparib Access Programme (RAP) was designed to provide early access to rucaparib for the above-mentioned indication, as well as for patients with BRCA-mutated Pt-S or platinum-resistant (Pt-R) OC and no therapeutic alternatives. METHODS: In this observational, retrospective study we analysed the efficacy and safety of rucaparib within the RAP in Spain. Hospitals associated with the Spanish Ovarian Cancer Research Group (GEICO) recruited patients with high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer treated with rucaparib 600 mg twice daily as maintenance or treatment (Pt-S/Pt-R) in the RAP. Baseline characteristics, efficacy, and safety data were collected. RESULTS: Between July 2020 and February 2021, 51 patients treated in 22 hospitals in the RAP were included in the study. Eighteen patients with a median of 3 (range, 1-6) prior treatment lines received rucaparib as maintenance; median progression-free survival (PFS) for this group was 9.1 months (95% confidence interval [CI], 4.2-11.6 months). Among 33 patients (median 5 [range, 1-9] prior treatment lines) who received rucaparib as treatment, 7 and 26 patients had Pt-S and Pt-R disease, respectively. Median PFS was 10.6 months (95% CI, 2.5 months-not reached) in the Pt-S group and 2.2 months (95% CI, 1.1-3.2 months) in the Pt-R group. Grade ≥ 3 treatment-emergent adverse events were reported in 39% of all patients, the most common being anaemia (12% and 15% in the maintenance and treatment groups, respectively). At data cut-off, 5 patients remained on treatment. CONCLUSION: Efficacy results in these heavily pre-treated patients were similar to those from previous trials. The safety profile of rucaparib in real life was predictable and manageable.

Activation of MET pathway predicts poor outcome to cetuximab in patients with recurrent or metastatic head and neck cancer.

BACKGROUND: Activation of the MET oncogene promotes tumor growth, invasion and metastasis in several tumor types. Additionally, MET is activated as a compensatory pathway in the presence of EGFR blockade, thus resulting in a mechanism of resistance to EGFR inhibitors. METHODS: We have investigated the impact of HGF and MET expression, MET activation (phosphorylation), MET gene status, and MET-activating mutations on cetuximab sensitivity in recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) patients. RESULTS: A single-institution retrospective analysis was performed in 57 patients. MET overexpression was detected in 58% patients, MET amplification in 39% and MET activation (p-MET) in 30%. Amplification was associated with MET overexpression. Log-rank testing showed significantly worse outcomes in recurrent/metastatic, MET overexpressing patients for progression-free survival and overall survival. Activation of MET was correlated with worse PFS and OS. In multivariate logistic regression analysis, p-MET was an independent prognostic factor for PFS. HGF overexpression was observed in 58% patients and was associated with MET phosphorylation, suggesting a paracrine activation of the receptor. CONCLUSIONS: HGF/MET pathway activation correlated with worse outcome in recurrent/metastatic HNSCC patients. When treated with a cetuximab-based regimen, these patients correlated with worse outcome. This supports a dual blocking strategy of HGF/MET and EGFR pathways for the treatment of patients with recurrent/metastatic HNSCC.

Atezolizumab Combined With Platinum and Maintenance Niraparib for Recurrent Ovarian Cancer With a Platinum-Free Interval >6 Months: ENGOT-OV41/GEICO 69-O/ANITA Phase III Trial.

PURPOSE: To evaluate atezolizumab combined with platinum-based chemotherapy (CT) followed by maintenance niraparib for late-relapsing recurrent ovarian cancer. METHODS: The multicenter placebo-controlled double-blind randomized phase III ENGOT-OV41/GEICO 69-O/ANITA trial (ClinicalTrials.gov identifier: NCT03598270) enrolled patients with measurable high-grade serous, endometrioid, or undifferentiated recurrent ovarian cancer who had received one or two previous CT lines (most recent including platinum) and had a treatment-free interval since last platinum (TFIp) of >6 months. Patients were stratified by investigator-selected carboplatin doublet, TFIp, BRCA status, and PD-L1 status in de novo biopsy and randomly assigned 1:1 to receive either atezolizumab or placebo throughout standard therapy comprising six cycles of a carboplatin doublet followed (in patients with response/stable disease) by maintenance niraparib until progression. The primary end point was investigator-assessed progression-free survival (PFS) per RECIST v1.1. RESULTS: Between November 2018 and January 2022, 417 patients were randomly assigned (15% BRCA-mutated, 36% PD-L1-positive, 66% TFIp >12 months, 11% previous poly [ADP-ribose] polymerase inhibitor after frontline CT, and 53% previous bevacizumab). Median follow-up was 28.6 months (95% CI, 26.6 to 30.5 months). Atezolizumab did not significantly improve PFS (hazard ratio, 0.89 [95% CI, 0.71 to 1.10]; P = .28). Median PFS was 11.2 months (95% CI, 10.1 to 12.1 months) with atezolizumab versus 10.1 months (95% CI, 9.2 to 11.2 months) with standard therapy. Subgroup analyses generally showed consistent results, including analyses by PD-L1 status. The objective response rate (ORR) was 45% (95% CI, 39 to 52) with atezolizumab and 43% (95% CI, 36 to 49) with standard therapy. The safety profile was as expected from previous experience of these drugs. CONCLUSION: Combining atezolizumab with CT and maintenance niraparib for late-relapsing recurrent ovarian cancer did not significantly improve PFS or the ORR.

Mediastinitis After Congenital Heart Surgery: Epidemiology, Clinical Features and Outcomes.

Mediastinitis after surgery for congenital heart disease has a great impact on morbidity and mortality. However, there are scarce studies focused on the epidemiology of postsurgical mediastinitis in pediatric patients. In this 18-year period retrospective study, the cumulative incidence of mediastinitis was low: 0.64%, (95% confidence interval: 0.36-1.1). Gram-negative bacilli were common (35%). The mortality rate was 7.1%, associated with fungal infection.

Comprehensive Approach to Genomic and Immune Profiling: Insights of a Real-World Experience in Gynecological Tumors.

Gynecological cancer accounts for an elevated incidence worldwide requiring responsiveness regarding its care. The comprehensive genomic approach agrees with the classification of certain tumor types. We evaluated 49 patients with gynecological tumors undergoing high-throughput sequencing to explore whether identifying alterations in cancer-associated genes could characterize concrete histological subtypes. We performed immune examination and analyzed subsequent clinical impact. We found 220 genomic aberrations mostly distributed as single nucleotide variants (SNV, 77%). Only 3% were classified as variants of strong clinical significance in BRCA1 and BRCA2 of ovarian high-grade serous (HGSC) and uterine endometrioid carcinoma. TP53 and BRCA1 occurred in 72% and 28% of HGSC. Cervical squamous cell carcinoma was entirely HPV-associated and mutations occurred in PIK3CA (60%), as well as in uterine serous carcinoma (80%). Alterations were seen in PTEN (71%) and PIK3CA (60%) of uterine endometrioid carcinoma. Elevated programmed death-ligand 1 (PD-L1) was associated with high TILs. Either PD-L1 augmented in deficient mis-matched repair (MMR) proteins or POLE mutated cases when compared to a proficient MMR state. An 18% received genotype-guided therapy and a 4% immunotherapy. The description of tumor subtypes is plausible through high-throughput sequencing by recognizing clinically relevant alterations. Additional concomitant assessment of immune biomarkers identifies candidates for immunotherapy.

Uso de ivabradina en el tratamiento de la taquicardia ectópica de la unión tras cirugía cardiaca / Use of ivabradine in pediatric post-operative junctional ectopic tachycardia

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Biweekly docetaxel and gemcitabine as neoadjuvant chemotherapy in stage II and III breast cancer patients: preliminary results of a phase II and pharmacogenomic study.

The purpose of this study is to evaluate the efficacy and safety of a biweekly neoadjuvant docetaxel/gemcitabine regimen in patients with histologically confirmed stage II and III breast cancer. In addition, a cDNA microarray study attempted to correlate pretreatment gene-expression profile with clinical and pathologic responses. Docetaxel 65 mg/m(2) was given in a 60-minute intravenous infusion followed by gemcitabine 2,500 mg/m(2) in a 30-minute intravenous infusion every 2 weeks for six cycles; prophylaxis with growth factors was allowed. Four cycles of standard AC (doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2)every 21 days) was routinely delivered to all patients postsurgery. Thirty patients are accrued on-study so far. The overall response rate for 24 evaluable patients was 79% (95% confidence interval, 9.7 to 53.5) with six complete responses and 13 partial responses. One patient (4%) out of 23 achieved a pathologic complete response in the breast at the time of definitive surgery. Breast conservation procedure was possible in 14 patients (61%). A total of 161 cycles has been delivered. Grade 1/2 alopecia and a mild grade 1/2 LDH increase were the most frequently reported adverse events (78% and 55% of cycles, respectively). Grade 3/4 neutropenia was reported in 18 cycles (11%). These preliminary results show that biweekly docetaxel and gemcitabine is an optimal regimen as neoadjuvant treatment of stage II and III breast cancer. In spite of the large tumor size, breast conservation was possible in 61% of the patients. In general, toxicity was very manageable.

Nodular lung schistosomiais lesions after chemotherapy for dysgerminoma.

We report an unusual case of pulmonary schistosomiasis in a traveler to Mali that was diagnosed 16 months after primary infection, one month after she finished chemotherapy for a malignant tumor. Serologic analysis showed marked eosinophilia. Our case emphasizes the need to detect parasitic infections in cancer patients with unexplained eosinophilia, particularly in immigrants and travelers to tropical countries.

Cuidados al final de la vida en la unidad de cuidados intensivos pediátricos. Empleo de técnicas de investigación cualitativa para el análisis del afrontamiento de la muerte y situaciones críticas / End-of-life care in the pediatric intensive care unit. Use of qualitative research techniques for analyzing coping with death and critical situations

Fundamento: En la última década, se aprecia un creciente interés por los aspectos más humanos de la enfermedad que se traduce en un acercamiento a la familia y a su sufrimiento. Objetivo: Conocer en profundidad la experiencia de los profesionales y de los padres de niños ingresados en la unidad de cuidados intensivos pediátricos (UCIP). Material y métodos: Se organizaron grupos focales (GF) de padres de hijos fallecidos o con secuelas graves ingresados en la UCIP los años 1999-2002. Asimismo, se desarrollaron reuniones de GF de profesionales. Se revisó desde el ingreso hasta la muerte y el seguimiento del duelo. Se recogieron las inquietudes y las necesidades expresadas por el personal sanitario. Resultados: Se contactó con 133 familias (40% de hijos fallecidos y 60% de hijos con secuelas), de los que acudieron un 75% y un 44%, respectivamente. Las madres acudieron más (61%) en el caso de fallecidos, y las parejas (51%), en el caso de niños con secuelas. Asimismo, se organizaron GF con 22 personas (5 médicos, 11 enfermeras y 5 auxiliares de enfermería). Se recogieron los principales problemas, discrepancias y soluciones. Se instauraron medidas de mejora acordes con la información recibida. Conclusiones: La aplicación de GF ha permitido el acercamiento a las necesidades y problemas más importantes de los padres de niños que ingresan en la UCIP, así como de los profesionales. Esta información ha facilitado la implantación de medidas de mejora de una forma realista y ajustada a estas necesidades

Background: In the last 10 years, there has been increasing concern for a more human approach to illness, which has led to a better understanding of families and their suffering. Objective: To gain greater insight into the experience of the parents of children admitted to the PICU and of the health workers in these units. Material and methods: Focus groups (FG) composed of parents with children who had died or who were having serious sequels were organized in the PICU from 1999-2002. Likewise, FG meetings with health professionals were set up. The period from admission to death and support for grieving families were reviewed. At the same time, the concerns and needs mentioned by health professionals were collected. Results: A total of 133 families were contacted by surface mail (40% had children who had died and 60% had children with sequels who survived); of these, 75% of the families in the first group and 44% of those in the second group attended the FG. Attendance by mothers (61%) was more frequent in the case of death, and attendance by couples (51%) was more frequent in children with sequels. Focus groups were organized with 22 health professionals (five physicians, 11 nurses and five nurses' aids). The main problems, discrepancies and solutions identified by the distinct groups were recorded. Improvement measures were implemented according to the available information. Conclusions: The use of FG allowed us to approach to the most important needs and problems of parents with children admitted to the PICU, as well as those of the heath workers in the unit. This information allowed improvement measures adjusted to these needs to be implemented in a realistic manner