Real-world safety and effectiveness of maintenance niraparib for platinum-sensitive recurrent ovarian cancer: A GEICO retrospective observational study within the Spanish expanded-access programme.

AIM: To describe patient characteristics, effectiveness and safety in a real-world population treated with niraparib in the Spanish expanded-access programme. PATIENTS AND METHODS: This retrospective observational study included women with platinum-sensitive recurrent high-grade serous ovarian cancer who received maintenance niraparib within the Spanish niraparib expanded-access programme. Eligible patients had received ≥2 previous lines of platinum-containing therapy, remained platinum-sensitive after the penultimate line of platinum and had responded to the most recent platinum-containing therapy. Niraparib dosing was at the treating physician's discretion (300 mg/day fixed starting dose or individualised starting dose [ISD] according to baseline body weight and platelet count). Safety, impact of dose adjustments, patient characteristics and effectiveness were analysed using data extracted from medical records. RESULTS: Among 316 eligible patients, 80% had BRCA wild-type tumours and 66% received an ISD. Median niraparib duration was 7.8 months. The most common adverse events typically occurred within 3 months of starting niraparib. Median progression-free survival was 8.6 (95% confidence interval [CI] 7.6-10.0) months. One- and 2-year overall survival rates were 86% (95% CI 81-89%) and 65% (95% CI 59-70%), respectively. Dose interruptions, dose reductions, haematological toxicities and asthenia/fatigue were less common with ISD than fixed starting dose niraparib, but progression-free survival was similar irrespective of dosing strategy. Subsequent therapy included platinum in 71% of patients who received further treatment. CONCLUSION: Outcomes in this large real-world dataset of niraparib-treated patients are consistent with phase III trials, providing reassuring evidence of the tolerability and activity of niraparib maintenance therapy for platinum-sensitive recurrent ovarian cancer. GOV REGISTRATION: NCT04546373.

Keratograph 5M As A Useful And Objective Tool For Evaluating The Ocular Surface In Limbal Stem Cell Deficiency.

PURPOSE: In limbal stem cell deficiency, both the Ocular Surface Disease Index (OSDI) questionnaire and tear break-up time (BUT) are comparable between traditional methods and the Keratograph 5M. In this study, we aimed to correlate OSDI with Keratograph 5M interviewed OSDI, as well as slit-lamp tear BUT with Keratograph 5M noninvasive tear break-up time (NIKBUT) in limbal stem cell deficiency. PATIENTS AND METHODS: Thirty-eight limbal stem cell-deficiency patients (76 eyes) from Virgen Macarena-Rocio Hospital (Seville, Spain) underwent this diagnostic test study. All patients completed the traditional OSDI. We measured the BUT, performed a Keratograph 5M analysis of NIKBUT first (employed for the analysis) followed by the average NIKBUT, the level of dryness, and conducted the OSDI questionnaire through an interview. For each pair of tests, we analyzed the means and applied an intraclass correlation coefficient (r), creating a Bland-Altman plot for data dispersion. RESULTS: Average values were 47.5 points (±25.8), and 47.3 points (±27.5) for traditional OSDI and Keratograph OSDI, respectively (P =0.87); the r value indicates good agreement (0.72). The Bland-Altman plot followed a linear pattern, and the results were similarly distributed. The NIKBUT mean was shorter than the BUT mean (P = 0.007); the r value indicates moderate agreement (0.574). The Bland-Altman plot formed an almost horizontal line, with almost all values between the mean and two standard deviations. CONCLUSION: Keratograph 5M is useful for the evaluation of the ocular surface in limbal stem cell deficiency. NIKBUT can substitute BUT based on its advantages of being noninvasive, objective, with intraobserver and interobserver repeatability and reliability. The Keratograph 5M OSDI is comparable to the traditional questionnaire.

1H-NMR Urinary Metabolic Profile, A Promising Tool for the Management of Infants with Human Cytomegalovirus-Infection.

Congenital human cytomegalovirus (HCMV) infection is the most common mother-to-child transmitted infection in the developed world. Certain aspects of its management remain a challenge. Urinary metabolic profiling is a promising tool for use in pediatric conditions. The aim of this study was to investigate the urinary metabolic profile in HCMV-infected infants and controls during acute care hospitalization. Urine samples were collected from 53 patients at five hospitals participating in the Spanish congenital HCMV registry. Thirty-one cases of HCMV infection and 22 uninfected controls were included. Proton nuclear magnetic resonance (1H-NMR) spectra were obtained using NOESYPR1D pulse sequence. The dataset underwent orthogonal projection on latent structures discriminant analysis to identify candidate variables affecting the urinary metabolome: HCMV infection, type of infection, sex, chronological age, gestational age, type of delivery, twins, and diet. Statistically significant discriminative models were obtained only for HCMV infection (p = 0.03) and chronological age (p < 0.01). No significant differences in the metabolomic profile were found between congenital and postnatal HCMV infection. When the HCMV-infected group was analyzed according to chronological age, a statistically significant model was obtained only in the neonatal group (p = 0.01), with the differentiating metabolites being betaine, glycine, alanine, and dimethylamine. Despite the considerable variation in urinary metabolic profiles in a real-life setting, clinical application of metabolomics to the study of HCMV infection seems feasible.

In vivo confocal microscopy indicates an inverse relationship between the sub-basal corneal plexus and the conjunctivalisation in patients with limbal stem cell deficiency.

BACKGROUND/AIMS: Limbal stem cell deficiency (LSCD) is characterised by a marked decrease in limbal stem cells. It is classified primarily using subjective slit-lamp observations. In vivo confocal microscopy (IVCM) can non-invasively provide objective information on the condition of the limbal niche, the corneal epithelial basal cell density and the corneal sub-basal nerve plexus density (SND). We here used IVCM to evaluate changes in SND to improve LSCD classification. METHODS: We evaluated and classified 38 patients (76 eyes, 44 with LSC and 32 control eyes) using the Rama, López-García and Deng (clinical and confocal) classifications and evaluated the concordance of the confocal and clinical classifications. We constructed a logistic regression model using multivariate analysis to correlate different degrees of conjunctivalisation with IVCM parameters and used receiver operating characteristic (ROC) curve analysis to establish the SND cut-off value with maximum diagnostic sensitivity and specificity. RESULTS: The classification systems correlated moderately at best (kappa, 0.449). The corneal SND of cases (6469±6295 µm/mm2) was less (p<0.001) than in controls (20911±4142 µm/mm2). The SND, but not basal cell density, played a protective role against conjunctivalisation (OR, 0.069; 95% CI 0.008-0.619; p=0.01). An SND cut-off value of 17 215 µm/mm2 yielded a sensitivity and specificity of 95.5% and 90.6%, respectively, for LSCD diagnosis. CONCLUSION: The density of the corneal sub-basal nerve plexus was inversely related to conjunctivalisation in LSCD. Further studies are needed to verify this and to elucidate the directionality between these factors.

Combined Hamartoma of the Retina and Retinal Pigment Epithelium in a Patient with Gorlin Syndrome: Spontaneous Partial Resolution of Traction Caused by Epiretinal Membrane.

Purpose. To describe the case of spontaneous resolution of epiretinal membrane in a patient with Combined Hamartoma of the Retina and Retinal Pigment Epithelium (CHR-RPE), in the clinical context of Gorlin Syndrome (GS). Methods. Observational case report of a 12-year-old female patient is presented. The diagnosis of CHRRPE was made by OCT and fundus examination, which showed a mound of disorganized tissue originating from retina and retinal pigment epithelium. Epiretinal membrane (EM) was also detected. Genetic study was performed to confirm the diagnosis of GS. Results. The patient was observed for 39 months, showing spontaneous resolution of the traction caused by the EM and improvement in visual acuity (VA), which was 20/80 at initial presentation, rising to 20/40 after follow-up period. Conclusions. The presence of EM in CHR-REP is a cause of reduction of visual acuity. Management of this condition is controversial; however, we would like to highlight that spontaneous resolution of the traction caused by EM is possible, resulting in recovery of VA.

Association between serum levels of C-reactive protein and response to treatment of chemotherapy-induced anemia in patients with solid tumors: a multicenter, prospective, observational study.

Our objective was to determine the association between C-reactive protein (CRP) levels at initiation of anemia treatment and response in solid tumor patients with chemotherapy (CT)-induced anemia. This was a multicenter, prospective, observational study which included adult patients with solid tumor initiating treatment for CT-induced anemia. Data were collected up to 16 weeks, or until premature discontinuation. We included 98 patients (median age 62.5 years, 64 % males, 57 % with ECOG 0-1, 85.7 % at stages III-IV and 54.1 % undergoing palliative CT). Mean (SD) Hb levels at baseline were 10.3 (0.9) g/dL (85.7 % < 11 g/dL) and median (Q1; Q3) CRP was 16.4 mg/L (3.9; 77.8) (68 % ≥ 5 mg/L). A total of 96 % of patients initiated erythropoiesis-stimulating agents (ESA) and iron supplementation; 4 % initiated iron monotherapy. After a median of 85 days, 65 % of patients had Hb ≥ 11 g/dL (in absence of transfusion) (mean change: +0.86 g/dL, 95 % confidence interval (CI) 0.53-1.19). A total of 8 patients required transfusion. A significant correlation (r = -0.39, p = 0.003) was observed between baseline CRP and final Hb levels. In the multivariate linear regression analysis, the independent predictors of higher final Hb levels were a high baseline Hb (adjusted ß = +0.69 g/dL for each g/dL of baseline Hb, 95 % CI 0.17-1.21) and a low log baseline CRP (-0.62 for each log mg/L, 95 %CI -1.22 to -0.02). Our results suggest that, in patients with solid tumors and CT-induced anemia, high CRP levels at treatment initiation predict a poor response to treatment with ESA and iron, independently from anemia severity at therapy initiation and from other patient and disease characteristics.

Effectiveness of darbepoetin alfa in a cohort of oncology patients with chemotherapy-induced anaemia. Relationship between variation in three fatigue-specific quality of life questionnaire scores and change in haemoglobin level.

BACKGROUND: Cancer patients with chemotherapy-induced anaemia (CIA) often experience cancer-related fatigue (CRF). Darbepoetin alfa (DA) once every 3 weeks (q3w) is an effective and well tolerated erythropoiesis-stimulating agent. This study evaluated DA effectiveness and psychometric properties of the Functional Assessment of Cancer Therapy Fatigue-Subscale (FACT-F) and the Fatigue Symptom Inventory (FSI) in CIA patients. METHODS: This was a single-centre, prospective study in 100 patients with solid tumour and moderate to severe CRF (visual analogue scale [VAS-F] ≥ 30 mm) who received DA 500 µg q3w during chemotherapy (CT). Clinical data, VAS-F, FACT-F and FSI scores were collected at the beginning and at the end of CT (EOCT). RESULTS: Mean age was 62.7 years (SD: 12.1), 53.0% were women, 92.0% had ECOG 0-1 and 64% had stage IV tumours. Mean haemoglobin (Hb) significantly increased from baseline 10.2 g/dl to 11.3 g/dl at EOCT. Sixty-five percent of patients showed haematopoietic response at any study point (Hb ≥ 12 g/dl or an increase of ≥ 2 g/dl from baseline), 77% achieved Hb ≥ 11 g/dl and 7% required blood transfusions from week 5 to EOCT. CRF improvement was demonstrated by significant changes in VAS-F, FACT-F and FSI scores (decreases of 21.54, 3.56 and 12.97 points, respectively). FACT-F and FSI questionnaires showed high internal consistency (Cronbach's alpha of 0.98 and 0.98 for FACT-F and FSI, respectively, at the end of study) and satisfactory intra-class coefficients (FACT-F, r=0.73; FSI, r=0.83). There were significant correlations between scores and Hb changes (FACT-F, r=-0.44; FSI, r=-0.54). CONCLUSIONS: DA 500 µg q3w showed effectiveness in improving Hb and inducing a clinically significant decrease in CRF of patients with solid tumours undergoing CT. The three instruments, VAS-F, FACT-F and FSI, could be suitable for assessing CRF.

Quantification in the serum of the catalytic fraction of reverse telomerase: a useful prognostic factor in advanced non-small cell lung cancer.

The purpose of this analysis was to study the association between the quantity of free circulating DNA and clinical variables in 99 advanced non-small cell lung cancer patients (NSCLC). The quantification in the serum of the gene of the catalytic fraction of telomerase (hTERT) by RT-PCR was used as a reference of the total amount of free DNA in blood. Patients were treated with cisplatin and docetaxel. The median hTERT level for patients in stage IIIB was 70.7 ng/ml vs. 53.1 ng/ml in patients in stage IV (p= 0.35). There was no association between hTERT values and therapy response, 53.9 ng/ml in the complete response (CR) + partial response (PR) group vs. 54.1 ng/ml in the stable disease (SD) + progressive disease (PD) group (p=0.23). In the multivariate analysis, hTERT was an independent predictive variable for time to progression (TTP) Hazard ratio (HR) 2.0, CI 95% 1.2-3.4, p=0.009) and overall survival (OS) (HR 2.4 CI 95% 1.3-4.3, p=0.004). The analysis of TTP and OS with a cut-off of hTERT at 40 ng/ml revealed that patients about this level had statistically poorer TTP (4 vs. 7 months, p= 0.009) and OS (5 vs. 15 months, p<0.0001). In conclusion, in advanced NSCLC, high serum hTERT levels may be a poor prognostic indicator for TTP and OS.

Weekly paclitaxel as second/third-line treatment in advanced non-small cell lung cancer patients: efficacy and tolerability.

BACKGROUND: The aim of the present study was to evaluate the efficacy and toxicity of weekly paclitaxel as second- or third-line treatment in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: The outcome measured in 37 patients were: response rates, symptom relief (dyspnoea, asthenia and pain), toxicity, overall survival (OS) and time to progression (TTP). RESULTS: Objective response was seen in 8%, stable disease in 27% and disease progression in 62%. Three paclitaxel courses reduced the frequency of WHO grade 2-3 dyspnoea and asthenia from 38% and 43% to 13.5% and &1%, respectively. Moderate to severe pain (VAS score 3-8) was reduced from 35.1% to 24.3%. Median OS was 38 weeks and TTP 12 weeks. Haematological toxicity included anaemia (30% grade 2-3) and neutropenia (8% grade 3). Nonhaematological toxicity included peripheral neuropathy (41% grade 1-2). CONCLUSION: In the routine outpatient setting, weekly paclitaxel is feasible, active and well-tolerated as second/third-line chemotherapy in patients with advanced NSCLC.