Beyond traditional therapies: clinical significance of complex molecular profiling in patients with advanced solid tumours-results from a Turkish multi-centre study.

OBJECTIVE: The objective of this multi-centre, real-world study was to examine the potential influence of comprehensive molecular profiling on the development of treatment decisions or adjustments for patients with advanced solid malignancies. We then evaluated the impact of these informed choices on patient treatment outcomes. METHODS: The study encompassed 234 adult patients (mean age: 52.7 ± 14.3 years, 54.7% women) who were diagnosed with solid tumours at 21 different medical centres in Turkey. Remarkably, 67.9% of the patients exhibited metastasis at the time of diagnosis. We utilized an OncoDNA (Gosselies, Belgium) platform (OncoDEEP) integrating next-generation sequencing with additional tests to harvest complex molecular profiling data. The results were analyzed in relation with two specific outcomes: (i) the impact on therapeutic decisions, including formulation or modifications, and (ii) associated treatment response. RESULTS: Out of the 228 patients with final molecular profiling results, 118 (50.4%) had their treatment modified, whilst the remaining 110 (47.0%) did not. The response rates were comparable, with 3.9 versus 3.4% for complete response, 13.6 versus 29.3% for partial response, 66.9 versus 51.7% for progressive disease and 15.5 versus 15.5% for stable disease for treatments informed and not informed by complex molecular profiling, respectively (P = 0.16). CONCLUSION: Our real-world findings highlight the significant impact of complex molecular profiling on the treatment decisions made by oncologists for a substantial portion of patients with advanced solid tumours. Regrettably, no significant advantage was detected in terms of treatment response or disease control rates.

[The effect of levosimendan and dobutamine treatment on QT dispersion in patients with decompensated heart failure: a prospective study]. / Levosimendan ve dobutamin tedavilerinin akut dekompanse kalp yetersizlikli hastalarda QT dispersiyonu üzerine etkisi: Prospektif bir çalisma.

OBJECTIVE: We investigated the effect of intravenous levosimendan on QT dispersion compared with intravenous dobutamine in patients with acute decompensated heart failure. METHODS: This prospective cohort study included 38 patients who were admitted with acute decompensated heart failure (New York Heart Association functional class III-IV). Twenty-five patients (11 men, 14 women; mean age 70.5 ± 11.13 years) were treated with levosimendan infusion and 13 patients (5 men, 8 women; mean age 71.08 ± 6.86 years) were treated with dobutamine infusion. Intravenous levosimendan was administered with an initial bolus dose of 12 µg/kg for 10 min, followed by a continuous infusion of 0.1 µg/kg/min for 1 hour and 0.1 µg/kg/min 23 hours. Intravenous dobutamine was administered with a continuous dose of 10 µg/kg /min for 24 hours. Transthoracic echocardiography was performed and electrocardiograms were obtained before and after drug infusions. QTc dispersion was defined as the difference between the maximum and the minimum QT intervals and the value was corrected for heart rate. Chi-square test, Wilcoxon test and Mann-Whitney U tests were used for data analysis. RESULTS: No significant differences were found before and after treatment of both levosimendan and dobutamine with respect to minimum QT intervals, maximum QT and QT dispersions. (Pretreatment and 24th hour values of levosimendan group were; 0.43 ± 0.04 s, 0.44 ± 0.04s; 0.49 ± 0.05s, 0.50 ± 0.05s; 0.06 ± 0.03s, 0.06 ± 0.03s; in dobutamine group values are - 0.39 ± 0.05 s, 0.41 ± 0.05s; 0.45 ± 0.05s, 0.48 ± 0.05s; 0.06 ± 0.04s, 0.06 ± 0.04s, respectively) (p>0.05). No side effects related to drugs were seen during follow-up in all two treatment groups. CONCLUSION: Our results suggest that, therapeutic doses of levosimendan infusion do not have a significant effect on QT parameters - the predictors of arrhythmias-, in patients with decompensated heart failure when compared with dobutamine infusion.

Primary adult soft tissue sarcomas: analysis of 294 patients.

We retrospectively analyzed 294 patients with primary soft tissue sarcoma followed between 1996 and 2002 in Ankara Oncology Hospital. There were 170 male and 124 female patients with the age range of 16-80 years. The primary tumor was in the extremity in 72.9% of the patients. We determined lung metastasis in 102 (85%) out of the 120 patients as distant metastasis. The most common adult sarcomas were liposarcoma (16.3%), malignant mesenchymal tumor (MMT) (13.9%), malignant fibrous histiocytoma (MFH) (11.2%), rhabdomyosarcoma (10.2%) and synovial sarcoma (10.2%). Seventeen patients (5.3%) had grade 1 tumor, 143 patients (52.2%) had grade 2 tumor, and 112 patients (41.4%) had grade 3 tumor. In 45 patients (15.3%), the grade of the tumors is unknown. The tumor size was 0 to <5 cm in 54 cases (19.4%), 5-10 cm in 117 cases (41.9%) and >10 cm in 108 cases (38.7%). In 15 cases (5.1%), tumor size was unknown. Ninety-five patients (32.4%) were treated with adjuvant chemotherapy, and 125 patients (42.7%)) were treated with palliative chemotherapy. Prognostic factors influencing the overall survival were tumor size, grade, adjuvant radiotherapy and chemotherapy. Adjuvant radiotherapy had influence on disease-free survival. While tumor grade and size showed a significant value for predicting local recurrence, grade, localization of tumor, adjuvant chemotherapy and radiotherapy had an impact on metastasis development. The 1-year overall survival for all patients was 73.4%, 3-year overall survival was 51.8%, and 5-year overall survival was 45.1%.