The impact of hybrid capture-based comprehensive genomic profiling on treatment strategies in patients with solid tumors

Objective: The development of bioinformatics and comprehensive genomic profiling (CGP) has provided insights into the ap-plicability and functionality of the genomic alterations (GA). In this study, we evaluated the impact of CGP on the treatment plan and outcomes in a significant number of patients. Material and Methods: We carried out a retrospective case-control study on 164 adult patients with advanced solid tumors from 15 oncology centers in Türkiye. Results: In all cases, CGP was performed within 23.8 [standard deviation (SD)±32.1] months of initial diagnosis. Non-small cell lung carcinoma, breast cancer, unknown primary carcinoma, colorectal carcinoma, and sarcoma were among the most common tumor types, accounting for 61.5% of all cases. CGP was performed immediately after the diagnosis of advanced cancer in 13 patients (7.9%). In 158 patients (96.4%), at least one GA was found as per the CGP report. Also, in the reports, the average tumor mutational burden (TMB) and GAs were 7.3 (SD±8.7) mut/Mb and 3.5 (SD±2.0), respectively. According to CGP reports, 58 patients had 79 evidence-based drug suggestions for their particular tumor type, whereas 97 patients had 153 evidence-based drug suggestions for another tumor type. After the primary oncologist interpreted the CGP reports, significant changes were made to the treatment of 35 (21.3%) patients. Conclusion: We strongly believe that in the future, high-TMB or other tumor-agnostic biomarkers will become much more afford-able, and CGP will serve as one of the major decision-making tools for the treatment of patients along with pathological, radiological or lab-oratory tests

Metronomic Temozolomide (mTMZ) and Bevacizumab—The Safe and Effective Frontier for Treating Metastatic Neuroendocrine Tumors (NETs): A Single-Center Experience

Addressing the persistent challenges in treating metastatic neuroendocrine tumors (NETs) demands ongoing refinement and innovation in therapeutic strategies. This study investigates the potential advantages of combining metronomic temozolomide (mTMZ) with bevacizumab for patients diagnosed with metastatic NETs, particularly focusing on those with a Ki-67 index under 55%. Data from 30 patients were analyzed, using key performance indicators such as progression-free survival (PFS), overall survival (OS), and response rates to therapy, to gauge the treatment’s efficacy. The results were encouraging: the median PFS recorded was 16.3 months, and the OS was 25.9 months. The disease control rate (DCR) reached an impressive 86.7%, and the objective response rate (ORR) stood at 63.3%. The treatment regimen was well-tolerated, with no reported instances of grade 4 toxicities. Such a safety profile indicates that this regimen may be particularly advantageous for older, fragile patients who might struggle with conventional dosage levels. These initial findings suggest that the mTMZ and bevacizumab combination could potentially rival the conventional temozolomide–capecitabine therapy in managing metastatic NETs. We aimed to meticulously assess the efficacy of the mTMZ and bevacizumab combination in treating metastatic NETs. Given the initial promising results, a more conclusive understanding of its efficacy will require further research through larger, multicenter prospective clinical trials

Phytochelatin and proline-related genes expression in tomato exposed to heavy metals

Heavy metals are one of the abiotic stress factor for plants, they effect the plant life cycles binding to sulfhydryl groups in amino acids and proteins. The presence of heavy metal in plant tissues changes the plant’s molecular, biochemical and physiological responses such as variations in gene expression, enzyme activities and amino acid content. This study aimed to determine the expression of P5CS and PCS genes to investigate their roles in the leaves of tomato plants subjected to increasing doses of heavy metals. The cultivars of tomato (Solanum lycopersicum cv.) were cultivated in plastic pots containing peat and garden soil (1:1) under greenhouse conditions. Three weeks after the plantings, the tomato plants were exposed to 10, 20 and 50 ppm doses of CdCI2, CuSO4 and Pb(NO3)2 salts. The leaves of tomato were harvested for sampling two weeks after the treatments and total RNA was extracted by using the Plant RNA Mini-Preps Kit. The first-strand cDNA was synthesized from the isolated RNA; the expression of the selected genes was detected by using RTqPCR with SYBR Green RT-PCR kit. Also, free proline content and metal-chelating ability was identified spectrophotometrically. The application of heavy metals significantly increased the expression of PCS1 gene in the leaves of tomato compared to control plants. The most evident expressions were observed in plants given the high doses of heavy metals. Transcript expression of P5CS1 changed depending on heavy metal doses; treatments of Cu (20 and 50 ppm), Cd and Pb (10 and 20 ppm) remarkably increased P5CS1 expression. The metal-chelating potency of the extract of tomato leaves exposed to Pb and Cd was higher than that of untreated plants. The proline content in the leaf extract significantly increased with the addition of 10 and 20 ppm of Pb and Cd, but significantly decreased at high doses (50 ppm) (p<0.05). The metal-chelating activity was higher in intervention plants cultivated in Pb and Cd-containing soils than in control plants (p<0.05). The results showed that the proline content had a positive correlation with P5CS1 transcript expression when the tomato plant is subjected to the three heavy metals. In addition, there was a positive relation between the PCS gene expression and metalchelating ability of Cd-stressed plants. In this context, the gene expressions of PCS1 and P5CS1 related with the PCs and proline content, respectively were correlated in the leaves of tomato under heavy metal stress. To further define and elucidate the responses of plants under stress conditions, the expression of genes and their corresponding enzymes associated with PCs and proline metabolisms, such as P5CR, P5CDH, PDH, POX, ProT, ɣ- ECS, and PC synthase, should be studied together to reveal the depth of responses in tomato subjected to various environmental conditions

Relatıonshıp Between Teachers’ Opınıons And Organızatıonal Confıdence Levels Of Communıcatıon Skılls Of School Admınıstrators

Bu araştırma Uşak ilindeki ilköğretim okulları yöneticilerinin iletişim yeterliliklerine ilişkin öğretmen görüşleri ile öğretmenlerin örgütsel güven düzeyleri arasındaki ilişki durumunu belirlemek amacıyla gerçekleştirilmiştir.Bu amaç doğrultusunda yapılan araştırma 2011–2012 eğitim öğretim yılında Uşak merkezde yer alan ilköğretim okullarında görev yapan 297 öğretmenin katılımıyla gerçekleşmiştir.Araştırmada veriler kişisel bilgi formu, iletişim yeterlilikleri ölçeği ile okullarda örgütsel güven ölçeği yardımıyla toplanmıştır. Araştırmaya katılanların demografik özelliklerinin belirlenmesinde frekans ve yüzde istatistiklerinden, iletişim yeterliliğine ilişkin görüşler ve örgütsel güven düzeylerinin belirlenmesinde ortalama ve standart sapma istatistiklerinden faydalanılmıştır.Öğretmenlerin demografik özelliklerine göre yöneticilerin iletişim yeterlik düzeylerine ilişkin görüşleri ve örgütsel güven düzeylerinin farklılaşma durumunun incelenmesinde Mann Whitney U Ve Kruskal Whallis H testlerinden faydalanılmıştır.Öğretmenlerin okul yöneticilerinin iletişim yeterliliği düzeylerine ilişkin görüşleri ve örgütsel güven düzeyleri arasındaki ilişkilerin belirlenmesinde korelasyon analizinden, faydalanılmıştır. Araştırma sonucunda okul yöneticilerinin “anlama-empati kurabilme” ve “sosyal rahatlık” iletişim yeterlilikleri arttıkça, öğretmenlerin örgütlerine olan güven düzeylerinin arttığı sonucuna ulaşılmıştı

Fourth versus eighth week surgery after neoadjuvant radiochemotherapy in T3-4/N0+ rectal cancer: Istanbul R-01 study.

İstanbul Bilim Üniversitesi, Tıp Fakültesi.BACKGROUND AND PURPOSE: The optimum duration between neoadjuvant radiochemotherapy and transmesorectal excision in locally advancedrectal cancer has not been defined yet. This randomized study was designed to compare the efficacy of four-week versus eight-week delay beforesurgery. METHODS: One-hundred and fifty-three patients with locally advanced low- or mid-rectum rectal adenocarcinoma were included in this single center prospective randomized trial. Patients were assigned to receive surgical treatment after either four weeks or eight weeks of delay afterchemoradiotherapy. Patients were followed for local recurrence and survival, and surgical specimens were examined for pathological staging and circumferential margin positivity. RESULTS: 4-week and 8-week groups did not differ with regard to lateral surgical margin positivity (9.2% vs. 5.1%, P=0.33, respectively), pathological tumor regression rate (P=0.90), overall survival (5-year, 76.5% vs. 74.2%, P=0.60) and local recurrence rate (11.8% vs. 10.3%, 0.77). Overall survival was better in patients with negative surgical margins (78.8% vs. 53.0%, P=0.04). Local recurrence rate was significantly higher among patients with positive surgical margin (28.5% vs. 9.3%, P=0.02). CONCLUSIONS: Intentional prolongation of the chemoradiotherapy-surgery interval does not seem to improve clinical outcomes of patients with locally advanced rectal cancer. Surgical margin positivity seems to be more important with this regard

Neoadjuvant chronomodulated capecitabine with radiotherapy in rectal cancer: a phase II brunch regimen study

İstanbul Bilim Üniversitesi, Tıp Fakültesi.Purpose The aim of this study was to evaluate efficacy and safety of chronomodulated capecitabine administered according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer. Methods Eighty-five patients with stage II and III rectal cancer were included. Patients received capecitabine (1,650 mg/m2 per day; 60 % dose at 8:00 AM and 40 % dose at 12:00 noon) administered during pelvic radiation (total 50.4 Gy in 28 fractions, 1.8 Gy daily dose between 2:00 p.m. and 4:00 p.m.). After chemoradiotherapy, patients underwent surgery. The primary endpoints were pathological complete response (pCR) rate and toxicity. Results In 17 patients (20 %), total tumor regression was achieved according to Dworak pathological grading system. Grade III diarrhea occurred in nine patients (10.5 %), while only one patient had grade 3 thrombocytopenia. Grade II or III proctitis were seen in nine (10.5 %) subjects, and grade I or II cystitis in six (6.9 %). Only three patients (3.3 %) developed hand and foot syndrome (both grade I–II). There were no grade IV toxicities. Conclusions Brunch Regimen for locally advanced rectal cancer consisting of neoadjuvant chronomodulated capecitabine and concurrent radiation therapy is effective and well tolerated with good safety profile, particularly with regard to the occurrence of hand and foot syndrome, in patients with locally advanced rectal cancer

Neoadjuvant hyperfractionated-accelerated radiotherapy with concomitant chemotherapy in esophageal cancer: phase II study.

İstanbul Bilim Üniversitesi, Tıp Fakültesi.PURPOSE: Concomitant use of chemotherapy and a radiation dose schedule that is more efficient compared to conventional radiotherapy may provide better outcomes in patients with esophageal cancer. This study aimed to assess the efficacy and tolerability of neoadjuvant cisplatin-basedchemotherapy and hyperfractionated accelerated radiotherapy regimen in this group of patients. METHODS AND MATERIALS: A total of 20 newly diagnosed treatment-naïve esophageal cancer patients were included in the study. Neoadjuvantcisplatin and 5-FU were given with 28-day intervals in a total of three courses. Along with the third course of chemotherapy, hyperfractionated accelerated radiotherapy (HART) was given with the following dose schedule: 5760 cGy/36 fr/16 day. RESULTS: All patients could receive the planned RT dose of 5760 cGy. Odynophagia was the most frequent grade III acute toxicity (50%). None of the acute toxicity reactions required treatment discontinuation. Grade III or higher subacute/late toxicity occurred in 10 patients (75%) including 5 deaths, mostly esophageal. Radiologically, 8 patients (40%) had complete response, 8 (40%) had partial response, and 3 (15%) had stable disease, with only 1 patient (5%) having progressive disease. Seven patients underwent surgery. Overall, 8 patients (40%) had local control. The 5 years overall survival rate was 38.1%. CONCLUSIONS: Neoadjuvant hyperfractionated accelerated radiotherapy plus chemotherapy may help to target local disease control and increase survival in patients with esophageal cancer. Further studies to improve neoadjuvant and radical chemoradiotherapy dose schedules are warranted for maximum tumor control rates with minimal toxicity

Adjuvant chemoradiotherapy after D2 resection in gastric cancer: a single-center observational study.

İstanbul Bilim Üniversitesi, Tıp Fakültesi.Purpose: Previous studies demonstrated survival benefits in association with the addition of chemoradiotherapy after surgery in gastric cancer. This study aimed to examine the efficacy in terms of loco-regional control and survival and safety of 5-FU-based adjuvant chemoradiotherapy after D2 curative surgery