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Öğe Effect of adjuvant chemotherapy in stage III cervical cancer patients treated with concurrent chemoradiation: A multicenter study(Karger, 2022) Atci, Muhammed Mustafa; Akagunduz, Baran; Demir, Metin; Dönmez Yilmaz, Binnur; Akin Telli, Tugba; Can, Orçun; Cil, Ibrahim; Goktas Aydın, Sabin; Ozyurt, Neslihan; Onder, Arif Hakan; Selvi, Oguzhan; Sakin, AbdullahIntroduction: A significant proportion of cervical cancer (CC) patients are diagnosed at a locally advanced stage. Concurrent chemoradiotherapy (CCRT) is the cornerstone of treatment for patients with locally advanced CC. However, the role of adjuvant chemotherapy (AC) after CCRT is controversial. In this study, we analyzed the efficacy of AC after CCRT in stage III CC patients. Methods: We performed a multicenter, retrospective analysis of 139 International Federation of Gynecology and Obstetrics stage III CC patients treated with CCRT of whom 45.3% received AC. Our goal was to determine the impact of AC on survival in these patients. Results: Five-year progression-free survival (PFS) was 37.5% and 16% in patients receiving CCRT with and without AC, respectively (p = 0.008). Median PFS was 30.9 months (CI 95% 14.8-46.9) and 16.6 months (CI 95% 9.3-23.9) in patients receiving CCRT with and without AC, respectively. Five-year overall survival (OS) was 78.2% and 28.4% in patients receiving CCRT with and without AC, respectively (p < 0.001). Median OS was 132.2 months (CI 95, %66.5-197.8) and 34.9 months (CI 95% 23.1-46.7) in patients receiving CCRT with and without AC, respectively. Conclusion: Our study suggests that AC provides OS and PFS benefit in stage III CC patients. Larger studies are needed to identify subgroups of patients who would benefit from AC.Öğe Efficacy of imatinib on advanced and refractory desmoid tumors: a retrospective study(Turkiye Klinikleri, 2022) Atçı, Muhammed Mustafa; Can, Orçun; Seçmeler, Saban; Sakin, Abdullah; Ay, Seval; Cihan, Sener; Selvi, Oğuzhan; Geredeli, CağlayanABS TRACT Objective: Our study aimed to analyze imatinib’s efficacy, tolerability, and safety in treating naive patients with unresectable and progressive desmoid tumors. Material and Methods: The data of patients who were ?18 years old diagnosed with desmoid tumors treated with imatinib were evaluated retrospectively regarding their demographic features, comorbidities, disease stage, pathological features of the tumor, response rates and progression-free survival (PFS). Results: In our study, 36 patients with advanced desmoid tumors receiving ima-tinib with a median age of 28 [interquartile range (IQR): 21-40] years-old of whom 58.3% were female were included. The patient’s complete response, partial response, stable disease, and progressive disease with imatinib 800 mg/day were 13.9%, 44.4%, 27.7%, and 13.9%, respec-tively. The Grade-3 adverse events, including neutropenia (n=3, 8.3%) and rash (n=3, 8.3%), were relieved after dose reduction. The median PFS was 29 months (95% confidence interval, 16-42 months) with imatinib, and only 3 (8.3%) patients were exitus due to disease progression during the follow-up (median: 43 months, IQR: 24.3-70.8). Conclusion: Our study provided clinical evidence of the efficacy and safety of imatinib in patients with desmoid tumors with real-world experience. However, appropriately designed randomized-controlled clinical trials are needed to explore the effectiveness of imatinib in desmoid tumors to provide an alternative management approach.Öğe Mitotic activity in gastrointestinal stromal tumors: Can we use phosphohistone h3 immunohistochemistry instead of hematoxylin and eosin for mitotic count?(KARE PUBL, 2022) Erhan, Selma Şengiz; Şensu, Sibel; Keser, Sevinç Hallaç; Kangal, Elis; Gül, Aylin Ege; Gundogan, Gokcen Alinak; Sakin, AbdullahObjectives: In gastrointestinal stromal tumors (GIST), malignancy potential is determined by the prognostic disease risk stratification based on mitosis, tumor size, and location. Phosphohistone H3 (PHH3) is an immunohistochemical marker showing mitotic activity in cells. In this study, we aimed to evaluate mitosis in GIST with PHH3, compare the results with hematoxylin and eosin (HE) stained slides, and examine its relationship with other prognostic data. Methods: Clinicopathological findings and survival were determined in GIST cases diagnosed between 2006 and 2017. The prognostic risk score was calculated according HE- and PHH3-based mitosis. The cases were classified as Group I: HE + and PHH3 + and Group II: HE + and PHH3-. They were also grouped as those diagnosed before and after 2012 and the staining results of HE and PHH3 were re-analyzed. Results: Ninety-eight cases were included in the study. Mitosis was detected with both HE and PHH3 in 63.3% of the cases (62/98 cases) (Group I) while in 36.7% of cases, it was detected with HE but not with PHH3 (Group II). In only two cases, the risk score changed with PHH3 (very low -> intermedier grade). The ratio of HE + and PHH3 + cases in 2012 and after was significantly higher than HE + and PHH3 - cases. A statistically significant relation was found between HE- and PHH3-based risk scores (p<0.05). There was a significant difference between HE-based risk score groups in terms of survival (p<0.05), while no difference was observed between the PHH3-based risk score groups (p>0.05). Conclusion: In GIST cases, PHH3 can be used to determine mitosis in more recent blocks, taking into account the technical conditions of the laboratory, but it does not seem to be superior to mitosis detected by HE. Research should continue on new survival determinants for GIST.Öğe The percentage of ALK-positive cells and the efficacy of first-line alectinib in advanced non-small cell lung cancer: is it a novel factor for stratification? (Turkish Oncology Group Study)(Springer, 2022) Kılıçkap, Saadettin; Paksoy, Nil; Bilgin, Burak; Sakin, Abdullah; Özcan, Erkan; Tatlı, Ali Murat; Hızal, Mutlu; Paksoy, Nail; Kahraman, SedatIntroduction: Alectinib is an effective second-generation ALK tyrosine kinase inhibitor (TKI) used in the first-line treatment of patients with advanced ALK-positive NSCLC. Recent studies demonstrated that the percentage of ALK-positive tumor cells in patient groups receiving crizotinib might affect outcomes. This study aimed to investigate whether the percentage of ALK-positive cells had a predictive effect in patients with advanced NSCLC who received first-line Alectinib as ALK-TKI. Materials and methods: This retrospective study included patients with advanced-stage NSCLC who received alectinib as a first-line ALK-TKI and whose percentage of ALK-positive cells was determined by FISH at 27 different centers. Patients who received any ALK-TKI before alectinib were not included in the study. Patients were separated into two groups according to the median (40%) value of the percentage of ALK-positive cells (high-positive group ? 40% and low-positive group < 40%). The primary endpoint was PFS, and the secondary endpoints were OS, ORR, and PFS of the subgroups based on different threshold values for the percentage of ALK-positive cells. Results: 211 patients were enrolled (48.3% female, 51.7% male) to study. 37% (n = 78) of the patients had received chemotherapy previously. After a median of 19.4 months of follow-up, the median PFS was not reached in the high-positive group (n = 113), but it was 10.8 months in the low-positive group (n = 98) (HR 0.39; 95% CI 0.25-0.60, p < 0.001). The median OS in the high-positive group was not reached, whereas it was 22.8 months in the low-positive group (HR 0.37; 95% CI 0.22-0.63, p < 0.001). ORR was significantly higher in the high-positive group (87.2 vs. 68.5%; p = 0.002). According to the cut-off values of < 20%, 20-39%, 40-59%, and ? 60%, the median PFS was 4.5, 17.1, and 26 months, respectively, and could not be reached in the ? 60% group. Conclusion: Our study demonstrated that the efficacy of alectinib varies significantly across patient subgroups with different percentages of ALK-positive cells. If these findings are prospectively validated, the percentage of ALK-positive cells may be used as a stratification factor in randomized trials comparing different ALK-TKIs.Öğe Real-life comparison of afatinib and erlotinib in non-small cell lung cancer with rare EGFR exon 18 and exon 20 mutations: a Turkish Oncology Group (TOG) study(Springer, 2022) Tatlı , Ali Murat; Erdem, Dilek; Göker, Erdem; Çelik, Emir; Demirci, Nebi Serkan; Sakin, Abdullah; Atçı , Muhammed Mustafa; Bayram, Ertuğrul; Akın Telli, Tuğba; Bilgin, Burak; Bilici, Ahmet; Akangündüz , Baran; Ballı, Sevinç; Demirkazık, Ahmet; Selçukbiricik, Fatih; Menekşe, Serkan; Çavdar, Eyyüp; Öztürk, Akın; Türkmen Bekmez, Esma; Turhal, Serdal; Kılıçkap, Sadettin; Yıldırım, Hasan Çağrı; Oyan, Başak; Aksoy, Asude; Paksoy Türköz, Fatma; Kut, Engin; Katgı, Nuran; Sakalar, Teoman; Akyol, Murat; Ellez, Halil İbrahim; Topçu, Atakan; Erdoğan, Atike Pınar; Pılancı, Kezban Nur; Hedem, Engin; Arak, Hacı; Akdeniz, Nadiye; Alan, Özkan; Yapar, Burcu; Nart, Deniz; Yumuk, Perran FuldenObjectives To compare the survival of frst- and second-generation tyrosine kinase inhibitors (TKIs) in patients with rare EGFR exon 18 and exon 20 mutation-positive non-small cell lung cancer (NSCLC). Materials and methods We retrospectively evaluated survival characteristics of 125 patients with EGFR exon 18 and exon 20 mutated NSCLC who received erlotinib or afatinib as frst line treatment between 2012 and 2021 from 34 oncology centres. Since exon 20 insertion is associated with TKI resistance, these 18 patients were excluded from the study. Results EGFR exon 18 mutations were seen in 60%, exon 20 mutations in 16%, and complex mutations in 24% of the patients with NSCLC who were evaluated for the study. There were 75 patients in erlotinib treated arm and 50 patients in afatinib arm. Patients treated with erlotinib had progression-free survival time (PFS) of 8.0 months and PFS was 7.0 months in the afatinib arm (p=0.869), while overall survival time (OS) was 20.0 vs 24.8 months, respectively (p=0.190). PFS of exon 18 mutated arm was 7.0 months, exon 20 mutated arm was 4.3 months, and complex mutation positive group was 17.3 months, and this was statistically signifcant (p=0.036). The longest OS was 32.5 months, seen in the complex mutations group, which was not statistically diferent than exon 18 and in exon 20 mutated groups (21.0 and 21.2 months, respectively) (p=0.323). Conclusion In this patient group, especially patients with complex mutations are as sensitive to EGFR TKI treatment similar to classical mutations, and in patients with rare exon 18 and exon 20 EGFR mutation both frst- and second-generation EGFR-TKIs should be considered, especially as frst- and second-line options.Öğe Real-world data on efficacy and safety of first-line alectinib treatment in advanced-stage, alk-positive non-small-cell lung cancer patients: A turkish oncology group study(Atypon, 2022) Hızal, Mutlu; Bilgin, Burak; Paksoy, Nail; Kılıçkap, Saadettin; Atcı, Muhammed Mustafa; Kahraman, Seda; Ayhan, Murat; Tural, Deniz; Yaman, Şebnem; Kutlu, Yasin; Korkmaz, Mustafa; Aksoy, Asude; Arak, Hacı; Korkmaz, Taner; Ak, Naziye; Akdeniz, Nadiye; Sakin, Abdullah; Fulden Yumuk, PerranAims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile.
