Real-World Patterns and Decision Drivers of Radiotherapy for Lung Cancer Patients in Romania: RADIO-NET Study Results.

Radiotherapy (RT) plays a crucial role in all stages of lung cancer. Data on recent real-world RT patterns and main drivers of RT decisions in lung cancer in Romania is scarce; we aimed to address these knowledge gaps through this physician-led medical chart review in 16 RT centers across the country. Consecutive patients with lung cancer receiving RT as part of their disease management between May-October 2019 (pre-COVID-19 pandemic) were included. Descriptive statistics were generated for all variables. This cohort included 422 patients: median age 63 years, males 76%, stages I-II 6%, III 43%, IV 50%, mostly adeno- and squamous cell carcinoma (76%), ECOG 0-1 50% at the time of RT. Curative intent RT was used in 36% of cases, palliative RT in 64%. Delays were reported in 13% of patients, mostly due to machine breakdown (67%). Most acute reported RT toxicity was esophagitis (19%). Multiple disease-, patient-, physician- and context-related drivers counted in the decision-making process. This is the first detailed analysis of RT use in lung cancer in Romania. Palliative RT still dominates the landscape. Earlier diagnosis, coordinated multidisciplinary strategies, and the true impact of the multimodal treatments on survival are strongly needed to improve lung cancer outcomes.

Real-World Testing Practices, Treatment Patterns and Clinical Outcomes in Patients from Central Eastern Europe with EGFR-Mutated Advanced Non-Small Cell Lung Cancer: A Retrospective Chart Review Study (REFLECT).

The targeted therapy with tyrosine kinase inhibitors (TKIs) against the epidermal growth factor receptor mutation (EGFRm) in advanced non-small cell lung cancer (NSCLC) changed the treatment paradigm. REFLECT study (NCT04031898) explored EGFR/T790M testing and treatment patterns in EGFRm NSCLC patients receiving first- or second-generation (1G/2G) EGFR TKIs as front-line (1L) in eight countries. Pooled data from Central Eastern Europe (CEE) countries from this study (Bulgaria, Poland, Romania, Slovenia) are presented here. This physician-led chart review study was conducted in patients with confirmed-EGFRm NSCLC initiating 1L 1G/2G EGFR TKIs between 2015-2018. The CEE cohort included 389 patients receiving 1L erlotinib (37%), afatinib (34%), and gefitinib (29%). Overall, 320 (82%) patients discontinued 1L, and 298 (77%) progression events were registered. Median progression free survival on 1L TKIs was 14.0 (95% CI: 12.6-15.6) months. Median overall survival from 1L start was 26.6 (95% CI: 24.1-29.0) months. Attrition rate between 1L and next line was 30%. Among patients with 1L progression, 200 (67%) were tested for T790M and 58% were positive. This first CEE analysis of treatments and outcomes in EGFRm NSCLC patients highlights the importance of using the most efficacious therapies currently available in 1L to reduce attrition and improve patient outcomes.

A randomized phase II trial of sequential gemcitabine plus vinorelbine followed by gemcitabine plus ifosfamide versus gemcitabine plus cisplatin in the treatment of chemo-naive patients with stages III and IV non-small cell lung cancer (NSCLC).

BACKGROUND: Third-generation platinum-based combinations are established as first-line treatment for advanced non-small cell lung cancer (NSCLC). Non-platinum regimens could be an alternative if they show similar efficacy with better tolerability. This randomized phase II trial compared the objective tumor response rate (ORR) of sequential gemcitabine plus vinorelbine followed by gemcitabine plus ifosfamide versus gemcitabine plus cisplatin. Secondary objectives included time to disease progression (TTP), overall survival and toxicity. METHODS: Chemo-naive patients with stages III and IV NSCLC and Karnofsky performance status >70 were assigned to receive either (a) gemcitabine 1000mg/m(2) plus vinorelbine 25mg/m(2) on days 1 and 8 for 2 cycles, followed by gemcitabine 1000mg/m(2) on days 1 and 8 plus ifosfamide 2000mg/m(2) on day 1 (GV-GI arm) for 2 cycles or (b) gemcitabine 1250mg/m(2) on days 1 and 8 with cisplatin 70mg/m(2) on day 1 (GC arm) for 4 cycles. RESULTS: Between July 2001 and January 2003, 102 patients were enrolled (50 on the GV-GI arm and 52 on the GC arm). Patient characteristics were balanced between arms (GV-GI arm: median age 59 years, 84% male, 22 stage IIIB, 24 stage IV, 4 stage IIIA; GC arm: median age 56 years, 87% male, 27 stage IIIB, 23 stage IV, 2 stage IIIA). Of the 101 patients evaluable for response, ORR was significantly higher on the GC arm than on the GV-GI arm (25% versus 6%, respectively; p=0.007). No complete responses occurred. TTP was longer on the GC arm than on the GV-GI arm (median 135 and 79 days, respectively), although this difference was not statistically significant (p=0.065). Survival was not significantly different between the arms (median 293 and 197 days, respectively; p=0.16). Although significantly more thrombocytopenia was reported on the GC arm (22% and 4%, respectively; p=0.02), it did not lead to more transfusions (15 transfusions in 5 patients versus 14 transfusions in 6 patients, respectively). There was no significant difference in other safety parameters between treatment arms. CONCLUSIONS: GC appears to produce better response in advanced NSCLC than GV-GI, with a trend towards longer TTP. Except for more thrombocytopenia with GC, similar toxicity profiles were observed.

Is the child an adult in miniature? Analysis of the role of regulatory decisions on antidepressive treatment for children and adolescents.

Depression in children and adolescents was accepted as an entity only 40 years ago, primarily because it was considered that children lacked the mature psychologic and cognitive structure necessary to experience the symptoms. There is a large body of evidence which confirmed the existence of disorder, but it was also shown that children and adolescents experience the whole spectrum of mood disorders, the incidence is increasing and the age at onset has fallen. Compared with adult depression, in children (6-12 years) and adolescents (13-18 years) a more insidious onset is seen, irritability is more frequent than sadness and association with other conditions (anxiety, conduct disorder, ADHD, learning disorder) is more often.

Humalog Mix 25 in patients with type 2 diabetes which do not achieve acceptable glycemic control with oral agents: results from a phase III, randomized, parallel study.

BACKGROUND: Humalog Mix 25 (Mix 25) is a premixed insulin mixture of 25% lispro and 75% neutral protamine lispro. Insulin lispro is an analog of human insulin. It is created when the amino acids at positions 28 and 29 of the B-chain of insulin are reversed. The natural sequence in human insulin at this position is proline at B28 and lysine at B29. The pharmacokinetic and pharmacodynamic profiles of insulin lispro indicate that it is more rapid acting, and therefore more physiological mealtime insulin than regular human insulin. OBJECTIVE: Primary objective of this study was to compare twice daily treatment with insulin lispro low mixture (Mix 25) to oral treatment with glibenclamide in patients with type 2 diabetes, with respect to the mean 2-hour postprandial blood glucose excursions after breakfast and dinner. SECONDARY OBJECTIVES: to compare the two treatments with regard to the following: hemoglobin A1c, fasting blood glucose, pre-dinner blood glucose, frequency of hypoglycemia, body weight, treatment satisfaction (by questionnaire). METHODS: The study described is a randomized, open-label, parallel group comparison of two treatment regimens in patients with type 2 diabetes. The study included two periods. The lead-in period lasted 10 +/- 7 days, all patients were taking glibenclamide. The treatment period lasted 16 weeks. Patients were randomized to receive either glibenclamide 15 mg daily or switch to Mix 25 before breakfast and dinner. Study design is illustrated in Fig. 1. Glycemic control was assessed by glycosylated hemoglobin (HbA1c) measurements, 4-point self monitoring blood glucose profiles, and patient reported hypoglycemia. One treatment satisfaction questionnaire (Appendix 1) was completed by each participant. RESULTS: 175 patients were included from the two participating countries (Romania--100 patients and Russia--75 patients). 85 were randomized to receive Mix 25 and 90 to glibenclamide arm. 172 patients were included in the efficacy analysis. Baseline patient characteristics did not show any differences between treatment groups for any of the demographic (age, gender, height, body weight, body mass index) or efficacy parameters (HbA1c or self monitored BG values). The mean age was 59.5 +/- 8.2 years, and 35.5% (61/172) were men. The mean body mass index was 27.2 kg/m2. The mean duration of type 2 diabetes was 10.2 +/- 6.6 years, and the mean duration of sulfonylurea treatment was 5.8 +/- 5.9 years. The mean HbA1c and fasting blood glucose levels were 10.07 +/- 1.4% and 11.6 +/- 2.8 mmol/L, respectively, in the glibenclamide group and 9.85 +/- 1.2% and 12.2 +/- 2.9 mmol/L, respectively, in the Mix 25 group. At the end point, all efficacy parameters were better improved in Mix 25 group (HbA1c, fasting blood glucose, 2-hour postprandial blood glucose). Mean HbA1c was significantly lower in the Mix 25 group than in the GB group (Mix 25, 8.5% +/- 1.3%; GB, 9.4 +/- 1.8%; P = 0.001). For all self-monitored blood glucose values (Fig. 2) a larger decrease from baseline was observed in the Mix 25 group: -1.4% versus -0.7% for HbA1c, (P = 0.004); -2.8 mmol/L versus -1.1 mmol/L for fasting blood glucose, (P < 0.01); -5.1 mmol/L versus -1.7 mmol/L for the morning 2-hour postprandial blood glucose, (P < 0.001); -2.2 mmol/L versus -0.8 mmol/L for the evening preprandial blood glucose, (P < 0.05); and 4.4 mmol/L versus -1.5 mmol/L for the evening 2-hour postprandial blood glucose, (P < 0.001). Percentage of patients experiencing at least 1 episode of hypoglycemia was--as predicted--higher in the Mix 25 group (44.7% versus 10.3%; P = 0.01). Patients expressed more satisfaction with Mix 25 than with GB, as measured by the weighted combined score on a treatment satisfaction questionnaire (2.0 +/- 1.3 vs 0.7 +/- 1.3). CONCLUSIONS: When glycemic control can no longer be achieved by oral antidiabetic agents, treatment with insulin should be considered as the next therapeutic option. Mix 25 provided good overall glycemic control, as well as patient treatment satisfaction.