[Experience of patients with immune-mediated inflammatory diseases seen in a multidisciplinary integrated care unit]. / Experiencia de los pacientes con enfermedades inflamatorias inmunomediadas atendidos en una unidad de atención integral multidisciplinar.

OBJECTIVE: To describe the aspects with the greatest impact on the satisfaction of patients treated in a multidisciplinary unit specialising in immune-mediated inflammatory diseases (IMIDs) and to identify areas for improvement in the care model. METHODS: Cross-sectional descriptive study using a satisfaction survey structured in three blocks: sociodemographic variables, functional aspects of the unit and satisfaction with the professionals. Immediate satisfaction was measured on aspects related to the care received, the physical structure and the likelihood of recommending the unit. RESULTS: A total of 168 patients completed the surveys, the mean score of overall satisfaction with the unit was 4.75 (SD:0.4). The regression model showed the relationship between overall satisfaction and unit signage (OR:3.558, p=0.045, 95% CI: 1.027-12.33), coordination between professionals (OR:9.043, p=0.000, 95% CI: 2.79-29.28) and participation in decision making (OR: 44.836, p=0.000, 95% CI: 5.49-365.97). In terms of immediate satisfaction, the overall Net Promoter Score (NPS) was 87 (excellent). The mean score for coordination with Primary Care was 4.54 (SD:0.8) and they scored waiting time to be seen with 4.49 (SD:0.8), so they have been considered an area for improvement The mean score for coordination with Primary Care was 4.54 (SD:0.8) and they scored waiting time to be seen with 4.49 (SD:0.8), so both were considered areas for improvement. CONCLUSIONS: Coordination between intra-centre professionals and patient participation in decision-making explain the excellent level of patient satisfaction. The monitoring of satisfaction has made it possible to implement immediate improvement actions.

Efficacy of immune checkpoint inhibitors in alveolar soft-part sarcoma: results from a retrospective worldwide registry.

BACKGROUND: Conventional cytotoxic drugs are not effective in alveolar soft-part sarcoma (ASPS). Immune checkpoint (programmed cell death protein 1/programmed death-ligand 1) inhibitors (ICIs) are promising drugs in ASPS. A worldwide registry explored the efficacy of ICI in ASPS. MATERIALS AND METHODS: Data from adult patients diagnosed with ASPS and treated with ICI for advanced disease in expert sarcoma centers from Europe, Australia and North America were retrospectively collected, including demographics and data related to treatments and outcome. RESULTS: Seventy-six ASPS patients, with a median age at diagnosis of 25 years (range 3-61 years), were registered. All patients received ICI for metastatic disease. Immunotherapy regimens consisted of monotherapy in 38 patients (50%) and combination in 38 (50%) (23 with a tyrosine kinase inhibitor). Among the 68 assessable patients, there were 3 complete responses and 34 partial responses, translating into an overall response rate of 54.4%. After a median follow-up of 36 months [95% confidence interval (CI) 32-40 months] since the start of immunotherapy, 45 (59%) patients have progressed on ICI, with a median progression-free survival (PFS) of 16.3 months (95% CI 8-25 months). Receiving ICI in first line (P = 0.042) and achieving an objective response (P = 0.043) correlated with a better PFS. Median estimated overall survival (OS) from ICI initiation has not been reached. The 12-month and 24-month OS rates were 94% and 81%, respectively. CONCLUSIONS: This registry constitutes the largest available series of ASPS treated with ICI. Our results suggest that the ICI treatment provides long-lasting disease control and prolonged OS in patients with advanced ASPS, an ultra-rare entity with limited active therapeutic options.

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.

Lenalidomide in combination with R-ESHAP in patients with relapsed or refractory diffuse large B-cell lymphoma: A phase 2 study from GELTAMO.

Diffuse large B-cell lymphoma (DLBCL) patients with relapsed or refractory (RR) disease have poor outcomes with current salvage regimens. We conducted a phase 2 trial to analyse the safety and efficacy of adding lenalidomide to R-ESHAP (LR-ESHAP) in patients with RR DLBCL. Subjects received 3 cycles of lenalidomide 10 mg/day on days 1-14 of every 21-day cycle, in combination with R-ESHAP at standard doses. Responding patients underwent autologous stem-cell transplantation (ASCT). The primary endpoint was the overall response rate (ORR) after 3 cycles. Centralized cell-of-origin (COO) classification was performed. Forty-six patients were included. The ORR after LR-ESHAP was 67% (35% of patients achieved complete remission). Patients with primary refractory disease (n = 26) had significantly worse ORR than patients with non-refractory disease (54% vs. 85%, p = 0.031). No differences in response rates according to the COO were observed. Twenty-eight patients (61%) underwent ASCT. At a median follow-up of 41 months, the estimated 3-year PFS and OS were 42% and 48%, respectively. The most common grade ≥3 adverse events were thrombocytopenia (70% of patients), neutropenia (67%) and anaemia (35%). There were no treatment-related deaths during LR-ESHAP cycles. In conclusion, LR-ESHAP is a feasible salvage regimen with promising efficacy results for patients with RR DLBCL.

Anthropogenic food subsidies reshape the migratory behaviour of a long-distance migrant.

Bird migratory journeys are often long and hostile, requiring high energetic expenditure, and thus forcing birds to pause between migratory flights. Stopover sites allow migrants to replenish fuel reserves and rest, being crucial for the success of migration. Worldwide, the increasing accumulation of waste on landfills and rubbish dumps has been described to provide superabundant food resources for many bird species not only during the breeding and wintering seasons but also during migration, being used as stopover sites. Using GPS-tracking data of juvenile white storks (Ciconia ciconia) during their first migration from the Iberia Peninsula to the sub-Saharan wintering grounds, we uncover the effects of stopping en route on individual migratory performance. Particularly, we examine the benefits of stopping at artificial sites (landfills and rubbish dumps) when compared to natural stopover sites (wetlands, agricultural or desert areas) and explore the influence of anthropogenic food resources on storks' migratory strategies. Overall, white storks spent up to one-third of the migration in stopovers. We found that birds that stopped for longer periods made more detours, increasing migration duration by half a day for each stopover day. Stopping more often did not reflect on increasing in-flight energetic efficiency nor the likelihood of completing the migration. Juvenile storks used artificial sites in 80 % of the stopover days, spending 45 % less time and 10 % less energy foraging than when using natural stopovers. While stopping in landfills did not translate into differences in migratory performance, individuals in poor body condition possibly rely on these sites to improve body weight before proceeding, enabling them to successfully complete migration. Artificial stopover sites are attractive and likely increase the number and duration of stops for white storks. Even though the consequences of arriving late at the wintering grounds are unknown, it can lead to cascading consequences, influencing individual fitness and population dynamics.

Primary intraosseous alveolar soft part sarcoma: Report of two cases with radiologic-pathologic correlation.

Alveolar soft part sarcoma (ASPS) accounts for less than 1 % of all soft tissue sarcomas. ASPS presents a poor prognosis and develops frequent metastases, especially in the lungs, brain and bones. Current therapies, such as surgery, radiotherapy and chemotherapy, are not fully effective and other alternative treatments are currently being studied. ASPS is predominantly found in the deep soft tissues of the lower extremities. To our knowledge, only thirteen primary intraosseous ASPS have been reported in the literature. In this study, we report two new cases of this exceedingly rare entity. Both cases already had multiple metastases since diagnosis; one of them represents the first case of a primary bone ASPS in the ulna and is also the primary intraosseous ASPS with the longest reported case of survival, after having maintained long periods of stabilization despite not having received any systemic treatment.

[Impact of the COVID-19 pandemic on patient safety incident and medication error reporting systems]. / Impacto de la pandemia COVID-19 en los sistemas de notificación de incidentes de seguridad del paciente y errores de medicación.

BACKGROUND AND AIM: To determine the impact of the COVID-19 pandemic on the epidemiology of safety incidents (SI) and medication errors (ME) reported to the CISEMadrid notification system in the hospital and primary care settings of the Madrid Health Service (SERMAS). MATERIALS AND METHODS: Observational and descriptive study with a retrospective analysis of data including all CISEMadrid notifications from 01-Jan-2018 to 31-Dec-2020, from 33 hospitals and 262 health care centres of the SERMAS. The two periods in 2020 with the greatest increase in COVID-19 cases were identified to compare incidents reported in the pre-pandemic and pandemic periods. RESULTS: 36,494 incidents were reported. Comparing both periods, an overall decrease in pandemic notifications of 60.7% was observed, being higher in primary care, falling to 33% of previous levels. The reduction in notifications was similar in the peaks and valleys of the waves. The three most frequent SIs in both periods and care settings were: diagnostic tests, medical devices/equipment/clinical furniture and organisational management/citations. In ME, dose failure and inappropriate selection were the most frequent in both settings and periods. There were no relevant differences in patient consequences in both periods. CONCLUSIONS: During the pandemic, patient safety notifications decreased although the most frequent types remained the same, as did their impact on the patient, both in hospitals and in primary care. The safety culture of organisations is a critical aspect for the maintenance of reporting systems.

Olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of BRCA status: a GEICO phase II trial (ROLANDO study).

BACKGROUND: There is limited evidence for the benefit of olaparib in platinum-resistant ovarian cancer (PROC) patients with BRCA wild-type tumors. This study investigated whether this combination of a DNA-damaging chemotherapy plus olaparib is effective in PROC regardless BRCA status. PATIENTS AND METHODS: Patients with high-grade serous or endometrioid ovarian carcinoma and one previous PROC recurrence were enrolled regardless of BRCA status. Patients with ≤4 previous lines (up to 5 in BRCA-mut) with at least one previous platinum-sensitive relapse were included; primary PROC was allowed only in case of BRCA-mut. Patients initially received six cycles of olaparib 300 mg b.i.d. (biduum) + intravenous pegylated liposomal doxorubicin (PLD) 40 mg/m2 (PLD40) every 28 days, followed by maintenance with olaparib 300 mg b.i.d. until progression or toxicity. The PLD dose was reduced to 30 mg/m2 (PLD30) due to toxicity. The primary endpoint was progression-free survival (PFS) at 6 months (6m-PFS) by RECIST version 1.1. A proportion of 40% 6m-PFS or more was considered of clinical interest. RESULTS: From 2017 to 2020, 31 PROC patients were included. BRCA mutations were present in 16%. The median of previous lines was 2 (range 1-5). The overall disease control rate was 77% (partial response rate of 29% and stable disease rate of 48%). After a median follow-up of 10 months, the 6m-PFS and median PFS were 47% and 5.8 months, respectively. Grade ≥3 treatment-related adverse events occurred in 74% of patients, with neutropenia/anemia being the most frequent. With PLD30 serious AEs were less frequent than with PLD40 (21% versus 47%, respectively); moreover, PLD30 was associated with less PLD delays (32% versus 38%) and reductions (16% versus 22%). CONCLUSIONS: The PLD-olaparib combination has shown significant activity in PROC regardless of BRCA status. PLD at 30 mg/m2 is better tolerated in the combination.

SEOM clinical guideline in ovarian cancer (2020).

Despite remarkable advances in the knowledge of molecular biology and treatment, ovarian cancer remains the leading cause of death from gynecologic cancer. In the last decade, there have been important advances both in systemic and surgical treatment. However, there is no doubt that the incorporation of PARP inhibitors as maintenance after the response to platinum-based chemotherapy, first in recurrent disease and recently also in first line, will change the natural history of the disease.The objective of this guide is to summarize the current evidence for the diagnosis, treatment, and follow-up of ovarian cancer, and to provide evidence-based recommendations for clinical practice.

Incidence of venous thromboembolic events in cancer patients receiving immunotherapy: a single-institution experience.

BACKGROUND: Cancer and cancer therapies have been associated with an increased incidence of venous thromboembolic events (VTE). However, the incidence of VTE in patients on immunotherapy has not been well characterized. The aim of this study was to assess the incidence of VTE in cancer patients receiving immunotherapy and ascertain its prognostic utility. MATERIALS AND METHODS: We conducted a single-institution retrospective study, including all cancer patients treated with anti-Programmed cell Death 1 (PD-1), anti-Programmed cell Death Ligand-1 (PD-L1), anti-Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4), a combination of anti-PD-1/anti-PD-L1 and anti-CTLA4 or a combination including any of these drugs with chemotherapy, antiangiogenic agents or both between June 2013 and April 2019 at La Paz University Hospital, Madrid (Spain). RESULTS: We selected 229 patients. VTE occurred in 16 of 229 patients (7%). VTE occurred more frequently in patients with lung cancer followed by melanoma. Female sex and melanoma were independently associated with an increased risk of VTE. 12 of 16 VTE (75%) were symptomatic. Progressive disease to immunotherapy [HR 31.60 (95% CI 11.44-87.22), p = 0.00], lung cancer [HR 2.55 (95% CI 1.34-4.86), p = 0.00] and melanoma [HR 2.42 (1.20-4.86), p = 0.01] were independently associated with shorter OS. VTE occurrence was not independently associated with shorter OS [HR 1.33 (95% CI 0.63-2.80), p = 0.44]. CONCLUSIONS: The incidence of VTE in cancer patients receiving immunotherapy in our study appeared to be similar to the incidence previously reported in other series of cancer patients treated with systemic therapies. VTE occurrence did not correlate with the prognosis. Further and prospective studies are needed to derive definitive conclusions.

Bevacizumab in recurrent ovarian cancer: could it be particularly effective in patients with clear cell carcinoma?

PURPOSE: Treatment of recurrent ovarian carcinoma is a challenge, particularly for the clear cell (CCC) subtype. However, there is a preclinical rationale that these patients could achieve a benefit from antiangiogenic therapy. To assess this hypothesis, we used the growth modulation index (GMI), which represents an intrapatient comparison of two successive progression-free survival (PFS). METHODS: We conducted a retrospective real-world study performed on 34 patients with recurrent ovarian cancer, treated with bevacizumab-containing regimens from January 2009 to December 2017. The primary endpoint was GMI. An established cut-off > 1.33 was defined as a sign of drug activity. RESULTS: 73.5% of patients had high-grade serous ovarian carcinoma (HGSOC), and 17.7% had CCC; 70.6% of patients received carboplatin/gemcitabine/bevacizumab, and 29.4% received weekly paclitaxel/bevacizumab. According to histological subtype, the overall response rate and median PFS were 52% and 14 months for HGSOC and 83.3% and 20 months for CCC, respectively. The overall population median GMI was 0.99; it was 0.95 and 2.36 for HGSOC and CCC, respectively. CCC subtype was significantly correlated with GMI > 1.33 (odds ratio 41.67; 95% confidence interval 3.6-486.94; p = .03). CONCLUSION: Adding bevacizumab to chemotherapy in recurrent CCC is associated with a remarkable benefit in this cohort. The efficacy of antiangiogenic drugs in CCC warrants further prospective evaluation.

The hallmarks of ovarian cancer: Focus on angiogenesis and micro-environment and new models for their characterisation.

Cancers develop by sustained growth, migration and invasion properties of tumour cells, supported by complex interactions with stromal cells within the tumour micro-environment. This review is focused on the latest discoveries regarding the highlighted role of angiogenesis and tumour micro-environment in ovarian cancer. This cancer milieu encompasses non-cancerous cells present in the tumour or nearby, including vessel-forming cells, fibroblasts and immune cells amongst others that work in a cooperative way with cancer cells, impacting tumour behaviour. Angiogenesis, migration and invasion, and more recently immune evasion, are cancer hallmarks clearly dependent on these supporting cells. Moreover, these stromal cells are more genetically stable than tumour cells and thus represent an attractive therapeutic target. A better understanding of the stromal cells function, and their complex interplay with cancer cells, will open additional areas to target, as the tumour-host interface.

Prognostic value of neutrophil-to-lymphocyte ratio and other inflammatory markers in patients with high-risk soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas (STS) have a high risk of relapse in spite of the use of (neo)adjuvant chemotherapy. In this context, looking for new prognostic biomarkers is an interesting field of research. Our aim is to analyze the prognostic impact of neutrophil-to-lymphocyte ratio (NLR) and other serum markers in patients with STS who received chemotherapy with curative intent. MATERIALS AND METHODS: This is a retrospective observational study. We included all patients with STS (primary tumor, local recurrence or resected metastatic disease) treated with high-dose ifosfamide and epirubicin with curative intent from January 2007 to December 2018. The pretreatment NLR and other serum markers were calculated, selecting the median as the cut-off value for the survival and multivariate analysis. RESULTS: Seventy-nine patients were included. Median NLR, platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) were 2.83, 174.05 and 3.25, respectively. Median progression-free survival (PFS) was significantly longer in patients with low NLR [not reached (NR) vs 21, 92 months, P < 0.01]. No significant differences were found for PFS regarding PLR or LMR. For overall survival (OS), a significant survival advantage was also found for patients with low NLR (NR vs 65.45 months, P = 0.01), without differences for PLR or LMR. In multivariate analysis, NLR remains an independent prognostic factor for PFS. CONCLUSION: In our cohort, low NLR was significantly associated with a longer PFS and OS, and is consolidated as an independent prognostic factor.

SEOM clinical guidelines for cervical cancer (2019).

Cervical cancer (CC) is the fourth most common cancer in women worldwide, strongly linked to high-risk human papilloma virus infection. In high-income countries, the screening programs have dramatically decreased the incidence of CC; however, the lack of accessibility to them in developing countries makes CC an important cause of mortality. Clinical stage is the most relevant prognostic factor in CC. The new FIGO staging system published in 2018 is more accurate than the previous one since it takes into account the lymph node status. In early stages, the primary treatment is surgery-with some concerns recently raised regarding minimally invasive surgery because it might decrease survival-or radiotherapy, whereas concomitant chemo-radiotherapy is the conventional approach in locally advanced stages. For recurrent or metastatic CC, the combination of chemotherapy plus bevacizumab is the preferred therapy. Immunotherapy approach based on checkpoint inhibitors is evolving as the election therapy following failure to platinum therapy.

[Perceived quality of care by frequent paediatric healthcare users: A qualitative approach]. / Calidad percibida en población hiperfrecuentadora infantil: una aproximación cualitativa.

INTRODUCTION: Assessing the perceived quality of a healthcare department by its users is essential in a quality management system. In Paediatric Emergency Departments (PED), the demand for urgent care has increased in recent years, as well as an increase in frequent attendance. Paying attention to the opinions of these habitual users by means of qualitative methodology is particularly suitable for assessing the quality of care and identifying opportunities to improve the PED. METHODS: Two focus groups were held with parents of patients (with and without a chronic disease) who visited the PED on 10or more occasions per year in a third level hospital. RESULTS: The participants were satisfied overall with the PED. The treatment received was very positively valued, and they never felt that they had received poorer care due to being frequent users. As main strengths, they also highlighted the professional expertise, the friendliness of staff, the quality of information given, the medication received on discharge from hospital, and the follow-up carried out by the PED. The major improvement opportunities identified included: the contagion risks, the lack of coordination between different levels of care, and the need to improve the inclusion of families in the health care process. CONCLUSIONS: Due to the contributions made by these parents, several improvement strategies have been introduced, such as the implementation of sharing information protocols in shift changes, professional training courses, the establishment of a liaison person between the PED and Primary Care, and a proposal to the Hospital Management Department to assess the identified needs.

[Evaluation of effectiveness of corrective measures arising from incident notifications in a paediatric emergency department]. / Evaluación de la efectividad de acciones correctivas derivadas de la notificación de incidentes en urgencias pediátricas.

OBJECTIVE: To analyse the effectiveness of corrective measures arising from the analysis of safety incident notifications in the Paediatric Emergency Unit. METHODS: A quasi-experimental, prospective, and single-centre study was carried out between 2015 and 2018. In the first phase, incidents notified throughout one year were analysed. Corrective measures were then implemented for 5 specific kinds of incidents. These incidents were finally compared to those notified within 12 months after the implementation of those measures. Results were expressed as relative risk and relative risk reduction. RESULTS: A total of 1587 safety incidents were notified (0.9% of patients treated) between January 2015 and December 2017. After implementation of corrective measures, there was a decrease in all kinds of incidents notifications analysed. The incidents related to patient identification were reduced by 60.9% (RR 0.39, 95% CI; 0.25-0.60), and those regarding communication between professionals were reduced by 74.5% (RR 0.25, 95% CI; 0.12-0.55). Incidents related to sedation and analgesic procedures totally disappeared. No significant reduction was found in incidents concerning the triage system, or in those related to rapid intravenous rehydration procedures. CONCLUSIONS: The implementation of improvement actions arising from the analysis of voluntary notification of incidents is an effective strategy to improve patient effective strategy to improve.

[Impact of a strategy to improve the quality of care and risk management in a paediatric emergency department]. / Impacto de una estrategia de mejora de calidad asistencial y gestión de riesgos en un servicio de urgencias pediátricas.

INTRODUCTION: Emergency departments are a high risk area for the occurrence of adverse events. The aim of this study is to analyse the impact of a strategy to improve the quality assurance and risk management in the notification of incidents in our Unit, and describe the improvement actions developed from the reported incidents. MATERIAL AND METHODS: A retrospective observational study was developed during one year, divided into two periods: P1 (Start: training session and implementation of the risk management process), and P2 (Start: feed-back session of incidents reported in P1 and improvement actions developed). In each period, the number of reported incidents in relation to the number of emergencies attended (‰) and the descriptive data of each incident were recorded. The improvement actions developed from the incidents reported in P1 were described. RESULTS: The number of notifications from P1 (4.1‰; 95%CI 3.2-5.0‰) increased in P2 (10.9‰; 95%CI 9.8-10.2‰, P<.001). The most frequent incidents in P1 were medication (33.3%), and identification errors (25.9%): both were significantly reduced in P2 (16.9%, P=.001 and 9.3%, P<.001, respectively). In P2, prescription errors of the P1 were reduced (35.9% vs 62.9%, P=.02). The factors of "Knowledge and training" (23.5%) were the most frequent in P1, decreasing in P2 (7.4%, P<.001). CONCLUSION: It is considered that the implementation of a risk management process, and the promotion of a safety culture, through training and feed-back sessions to all professionals, contributed to increase the volume of notifications in our Unit. The voluntary and anonymous reporting of incidents is useful to identify risks, and plan corrective measures, contributing to improve quality assurance and patient safety.

Safety and dose modification for patients receiving niraparib.

Background: Niraparib is a poly(ADP-ribose) polymerase inhibitor approved in the USA and Europe for maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In the pivotal ENGOT-OV16/NOVA trial, the dose reduction rate due to treatment-emergent adverse event (TEAE) was 68.9%, and the discontinuation rate due to TEAE was 14.7%, including 3.3% due to thrombocytopenia. A retrospective analysis was carried out to identify clinical parameters that predict dose reductions. Patients and methods: All analyses were carried out on the safety population, comprising all patients who received at least one dose of study drug. Patients were analyzed according to the study drug consumed (i.e., as treated). A predictive modeling method (decision trees) was used to identify important variables for predicting the likelihood of developing grade ≥3 thrombocytopenia within 30 days after the first dose of niraparib and determine cut-off points for chosen variables. Results: Following dose modification, 200 mg was the most commonly administered dose in the ENGOT-OV16/NOVA trial. Baseline platelet count and baseline body weight were identified as risk factors for increased incidence of grade ≥3 thrombocytopenia. Patients with a baseline body weight <77 kg or a baseline platelet count <150 000/µl in effect received an average daily dose ∼200 mg (median = 207 mg) due to dose interruption and reduction. Progression-free survival in patients who were dose reduced to either 200 or 100 mg was consistent with that of patients who remained at the 300 mg starting dose. Conclusions: The analysis presented suggests that patients with baseline body weight of <77 kg or baseline platelets of <150 000/µl may benefit from a starting dose of 200 mg/day. ClinicalTrials.gov ID: NCT01847274.

Analysis and design of fibers for pure-quartic solitons.

The recently discovered pure-quartic solitons, arising from the interaction of quartic dispersion and Kerr nonlinearity, open the door to unexplored soliton regimes and ultrafast laser science. Here, we report a general analysis of the dispersion and nonlinear properties necessary to observe pure-quartic solitons in optical platforms. We apply this analysis, in combination with numerical calculations, to the design of pure-quartic soliton supporting microstructured optical fibers. The designs presented here, which have realistic fabrication tolerances, support unperturbed pure-quartic soliton propagation providing access to an unmatched platform to study novel soliton physics.