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  • Küçük Resim
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    The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study
    (Springer, 2021) Akdeniz, Nadiye; Kaplan, Muhammet Ali; Uncu, Doğan; İnanç, Mevlüde; Kaya, Serap; Dane, Faysal; Küçüköner, Mehmet; Demirci, Ayşe; Bilici, Mehmet; Durnalı, Ayse Gök; Koral, Lokman; Şendur, Mehmet Ali Nahit; Erol, Cihan; Türkmen, Esma; Ölmez, Ömer Fatih; Açıkgöz, Özgür; Laçin, Şahin; Şahinli, Hayriye; Urakçı, Zuhat; Işıkdoğan, Abdurrahman
    Purpose We aim to compare the efficiency and toxicity of three different 5-fluorouracil (5-FU) administration types in 5-FU, leucovorin, and oxaliplatin (FOLFOX) combination treatment for adjuvant therapy in colorectal cancer (CRC). Methods Five hundred and seventy patients with stage III colorectal carcinoma who received different FOLFOX regimens after curative resection were included. Patients were divided into three groups as FOLFOX-4, modified FOLFOX-6 (mFOLFOX-6), and mFOLFOX-4 for comparison of toxicity and disease-free survival (DFS) and overall survival (OS) times. Results Three-year DFS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 65%, 72%, and 72%, respectively. Five-year OS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 69%, 75%, and 67%, respectively. There was no statistically significant difference between the three treatment groups in terms of DFS and OS (p = 0.079, and p = 0.147, respectively). Among grade 1-2 adverse events (AE), thrombocytopenia, neuropathy, and stomatitis were more common in the mFOLFOX-6-treated group. The frequency of grade 1-2 nausea and vomiting were similar in mFOLFOX-6 (36.3% and 24%, respectively) and mFOLFOX-4 (32.4% and 24.7%, respectively) groups but were higher than that in the FOLFOX-4 (19.5% and 11.3%, respectively) group. Among the most common grade 3-4 AE, neutropenia (53.4%, 9%, and 13.5%, respectively) and diarrhea (10.5%, 2.2%, and 2.4, respectively) were more common in FOLFOX-4. The rate of anemia and febrile neutropenia was similar in treatment groups (p = 0.063, and p = 0.210, respectively). Conclusion In the adjuvant treatment of stage III CRC patients, three different 5-FU administration types in FOLFOX combination treatment can be used with similar efficiency and manageable toxicity.
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    Comparison of three different chemotherapy regimens for concomitant chemoradiotherapy in locally advanced non-small cell lung cancer
    (Springer Japan Kk, 2020) Akdeniz, Nadiye; Kucukoner, Mehmet; Kaplan, Muhammet Ali; Urakci, Zuhat; Karhan, Ogur; Sezgin, Yasin; Bilen, Erkan
    Purpose The optimal chemotherapy regimen for concurrent chemoradiation in locally advanced non-small cell lung cancer (NSCLC) remains unclear. Cisplatin-etoposide regimen related toxicity is high, weekly regimens have been investigating. We aimed to compare the efficacy and safety of different concurrent chemotherapy regimens in the context. Methods A total of 225 patients with locally advanced, unresectable stage III NSCLC were included. Patients who were treated with weekly docetaxel-platin (DP), paclitaxel-platin (PP) and standard dose etoposide-platin (EP) chemotherapy regimens were selected and divided into groups for the comparison of toxicity, response rate, progression free survival (PFS), and overall survival (OS) times. Results There was a statistically significant difference between overall response rate of each treatment groups (DP: 96.1%, PP: 94% and EP: 76.7%,p < 0.001). The median PFS time of patients who were treated with DP, PP and EP was 16, 15 and 13.3 months, respectively (p = 0.435). The median OS time of patients treated with DP, PP and EP was 19.2, 29.7 and 28.3 months, respectively (p < 0.001). The rates of adverse events such as nausea, vomiting, neuropathy and anaphylaxis was similar. Grade 1-2 mucositis or esophagitis, anemia, pneumonitis were significantly higher in PP group than other groups. However, hematologic toxicities were higher in the EP group than other groups. Conclusions Compared to the weekly chemotherapy regimens with the standard dose, our study demonstrated similar PFS, but a prolonged OS with the EP regimen. The clinical response rate of weekly regimens was better than the full-dose regimen. Adverse events and toxicity rates were different and depended on the type of chemotherapy regimen used.
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    Öğe
    The effect of exercise on disease-free survival and overall survival in patients with breast cancer
    (Springer London Ltd, 2022) Akdeniz, Nadiye; Kaplan, Muhammet Ali; Kucukoner, Mehmet; Urakci, Zuhat; Lacin, Sahin; Ceylan, Emre Husnu; Isikdogan, Abdurrahman
    Background Positive effects of exercise in cancer patients have been reported. Aim To investigate whether intensity, duration, and timing of exercise affect disease relapse and mortality risk in patients with breast cancer (BC). Methods Patients with local or locally advanced stages of BC between January 2018 and January 2020 were recruited in the study. Sociodemographic and clinicopathological characteristics of patients were recorded. Exercise evaluation was performed by preparing a questionnaire and asking the patients face-to-face questions in the outpatient clinic. Results Risk of relapse was 58% lower in patients who exercised than inactive patients (p = 0.004). Patients who exercised for 2 to 5 days per week had a 63% lower relapse risk than inactive patients (p = 0.010). Risk of relapse was 66% lower in the patients who exercised for less than 1 h or 3 metabolic equivalent of task (MET)-hours per week when compared to inactive patients (p = 0.037). Similarly, relapse risk was 62% lower in patients who exercised between 1 to 3 h or 3 to 8.9 MET-hours per week than inactive patients (p = 0.026). Mortality risk was lower in patients who exercised than patients who did not (p = 0.027). A significantly decreased mortality risk was found in both groups that included patients who exercised for 1 to 5 days per week and patients who exercised for less than 3 h or 9 MET-hours per week when compared to inactive patients. Conclusion Exercise was associated with decreased relapse and mortality rates in patients with BC. Therefore, exercise should be recommended to BC patients as a significant component of the treatment.
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    The Efficacy and Safety of Treatment Regimens Used in the First-Line Setting in Metastatic Pancreatic Cancer Patients A Multicenter Real-Life Study
    (Lippincott Williams & Wilkins, 2022) Akdeniz, Nadiye; Kaplan, Muhammet Ali; Inanc, Mevlude; Uncu, Dogan; Ergun, Yakup; Kucukoner, Mehmet; Demirci, Ayse
    ObjectiveThe aim of the study is to compare the efficacy and safety of 3 chemotherapy regimens used as first-line treatments in the real-life management of metastatic pancreatic cancer.MethodsA total of 218 patients were included in this multicenter study. Gemcitabine (Gem, n = 71), gemcitabine-cisplatin (Gem-Cis, n = 91), and FOLFIRINOX (a combination of leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin [FFX], n = 56) treatments were compared.ResultsOverall response rate was significantly higher in the FFX group (50.0%) than in the Gem (28.2%) and Gem-Cis (27.5%) groups (P = 0.010). Median progression-free survival (8.4 vs 4.6 and 5.5 months, respectively, P < 0.001) and overall survival (16.4 vs 8.1 and 8.7 months, respectively, P = 0.002) were significantly longer in the FFX group than in the Gem and Gem-Cis groups. Toxicity of any grade was noted in 46 (64.8%), 56 (61.5%), and 49 (87.5%) patients in the Gem, Gem-Cis, and FFX groups, respectively (P = 0.003).ConclusionsIn our study, FFX regimen provides a significant advantage over the other treatment regimens in terms of response rates and survival. Treatment toxicity was more frequent but manageable with the FFX regimen.
  • Küçük Resim
    Öğe
    Evaluation of bleeding symptoms and laboratory parameters related to bleeding in sisters of patients with hemophilia A and B
    (Pergamon-Elsevier Science LTD, 2021) Akdeniz, Nadiye; Karakuş, Abdullah; Yıldız, İsmail; Ayyıldız, Mehmet Orhan
    Introduction: Our purpose was to determine the bleeding risk of obligate and potential carriers, highlight the prophylactic applications before interventions for families and physicians. Method: Forty-six sisters who had at least one family member with hemophilia A or B were included. Laboratory parameters were tested.Bleeding tendency interrogated by a detailed questionnaire.The results were compared with 43 healthy female controls. Results: Mean factor activity levels were significantly lower in sisters than control subjects (p = 0,004). Bleeding score was higher in sisters than controls (p = 0.001). Prolonged bleeding after minor injury was significantly higher in the sisters than control subjects (p = 0.008). Requiring further treatment due to prolonged bleeding after tooth extraction was significantly higher in sisters (p = 0.001). Sisters had postpartum hemorrhage lasting longer than 6 weeks than controls (p = 0.025). Menstrual period lasted longer in the sisters than controls (p < 0.001). Spontaneous epistaxis, oral and gingival bleeding were more frequently observed in sisters whose factor activity levels were 60 % or below (p = 0.014 and p = 0.047, respectively). There was no statistically significant difference between the severity of hemophilia in the affected family member and the factor levels in the sisters (p = 0.398).Spontaneous epistaxis has found to be significantly associated with the hemophilia severity in the family (p = 0.004). Conclusion: Clotting factor levels were found to be lower in the sisters and associated with spontaneous epistaxis, oral and gingival bleeding.Also, regardless of clotting factor levels, sisters significantly experienced more bleeding problems.Our study demonstrated the importance of taking precautions for prolonged bleeding in cases where medical interventions are inevitable in these patients.
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    Hemofili A ve B hastalarının kız kardeşlerinde kanama semptomları ve kanamaya yönelik laboratuvar parametrelerinin değerlendirilmesi
    (2016) Akdeniz, Nadiye; Ayyıldız, Mehmet Orhan
    Giriş ve amaç: Hemofili A (faktör 8 eksikliği ) ve B (faktör 9 eksikliği) genetik olarak X'e bağlı resesif geçiş gösterir ve erkekleri etkiler. Ancak bu kişilerin anneleri ve kızları genetik bozukluğun taşıyıcılarıdır. Hemofililer erkeklerde kanama eğilimi açısından çok iyi bilinmesine rağmen bayan taşıyıcılarda nadiren farkına varılmaktadır. Oysaki bayan taşıyıcılar karşımıza sadece artmış kanama eğilimi ile değil bazen sık ve aşırı kanama ile de gelebilmektedir. Çalışmadaki amacımız hemofilili hastaların kız kardeşlerindeki faktör düzeylerini ve kanama riskini belirleyip, müdahaleler öncesi profilaktik uygulamalar ve uzamış kanamalar açısından ailelerin ve hekimlerin dikkatini bu yöne çekmektir. Materyal ve metod: Hemofili hastalarının kız kardeşlerinde laboratuvar ve klinik kanama eğilimlerini belirlemek için çalışma dizaynı yapıldı. Çalışmaya ailesinde en az bir hemofili A veya B hastası olan, menarş gören 46 kız kardeş dahil edildi. Sağlıklı, hemofili A veya B taşıyıcısı olmadığı bilinen 43 kadın kontrol grubu olarak seçildi. Bu amaçla kız kardeşlerde laboratuvar olarak aPTT, tam kan, VWF, kanama zamanı ve erkek kardeşi hemofili A hastası olanlarda faktör 8, hemofili B hastası olanlarda faktör 9 düzeyleri çalışıldı. Kontrol grubu ile karşılaştırıldı. Kız kardeşlerin kişisel karakteristikleri, etkilenmiş olan aile bireylerinde hemofilinin karakteristikleri, zorunlu taşıyıcılarda hemofilili çocuk sayısı, spontan ve uyarılmış kanamalarda uzamış kanama eğilimlerine ilişkin detaylı öyküleri anket formu düzenlenerek sorgulandı. Aynı sorgulama kontrol grubunda da yapıldı. Bulgular: Kız kardeşlerin ailelerinde hemofili A olanların sayısı 39 (%84,8), hemofili B olanların sayısı 7 (%15,2) idi. Ailede hafif hemofilili hasta olan kız kardeş sayısı 6 (%13), orta hemofilili olan 4 (%8,7), ağır hemofilili olan 36 (%78,3) kişiydi. Hemofilili hastaların kız kardeşlerinin laboratuvar bulguları kontrol grubu ile karşılaştırıldığında ortalama faktör düzeyleri anlamlı olarak kız kardeşlerde düşük bulundu (sırasıyla 60,13±37,91%, 80,04±23,35 % , p: 0,004). Faktör 8 ve 9 ayrı ayrı değerlendirildiğinde kız kardeşlerde faktör 8 düzeyi kontrol grubuna göre anlamlı olarak düşük bulunurken (sırasıyla 53,77±32,07 %,75,06±20,55 %, p:0,001), faktör 9 düzeyleri arasında anlamlı farklılık saptanmadı (sırasıyla 90,36±50,41%, 110,71±15,02%, p:0,361). Kız kardeşlerin aPTT değerleri kontrol grubu ile karşılaştırıldığında kız kardeşlerde aPTT 'nin anlamlı olarak uzadığı görüldü (sırasıyla 30,5±4,08 sn, 27,2±3,13 sn, p: 0,000). Spontan burun kanaması ve ayrıca spontan deri morarmaları sorgulandığında kız kardeşlerden 13 'ünde (%28,3) tanımlanmış olup kontrol grubunda 7 'sinde (%16,3) spontan burun kanaması ve 8 'inde (18,6) spontan deri morarmaları tarif edilmiştir. Kız kardeşlerden 7 'sinde (%15,2) küçük yaralanmalar sonrası kanama 10 dakikadan uzun sürmüşken kontrol grubunda küçük yaralanmalar sonrası kanama 10 dakikadan kısa sürmüştür. Kız kardeşlerden diş çekimi yapılan 27 kişiden 12'sinde (%44,4), kontrol grubunda 31 kişiden 2 'sinde (%6,5) diş çekimi sonrası uzamış kanama nedeni ile ilave tedavi gerekmiştir. Kız kardeşlerden cerrahi yapılan 17 kişiden 6 'sının (%35,1) kontrol grubundan 22 kişiden 2 'sinin (%9,1) cerrahi sonrası uzamış kanama nedeni ile tedavi gereksinimi olmuştur. Doğum yapan 12 kız kardeşten 3 'ünün (%25) doğum sonrası kanaması 6 haftadan uzun sürmüştür. Kız kardeşlerden 15 'inde (%32,6) mensturasyon kanaması 7 günden uzun sürmekteyken kontrol grubunda bir kişi 7 günden uzun süren mensturasyon kanaması tarif etmiştir. Kırk altı kız kardeşten 21 'inin (%45,7) faktör düzeyi %5-40 arasında, 7 'sinin ( %15,2) faktör düzeyi %41-60 arasında ve 18 'inin (%39,1) faktör düzeyi %61 ve üzerinde bulundu. Pıhtılaşma faktör düşüklüğü ile spontan burun kanaması, ağız içi ve diş eti kanamaları arasında ilişki saptandı (p<0,05). Hemofili hastalarının kız kardeşleri, pıhtılaşma faktör düzeylerinden bağımsız olarak sağlıklı gruba göre daha fazla küçük yaralanmalar sonrası uzamış kanama, artmış yaralanma sıklığı, diş çekimi sonrası uzamış kanama nedeni ile ilave tedavi gereksinimi, uzamış menstural periyod kanaması ve doğum sonrası uzamış kanama tarif etmektedirler (p<0,05). Spontan burun kanaması (p:0,176), spontan deri morarmaları (p:0,284), operasyon sonrası uzamış kanamalarda (p:0,260) iki grup arasında anlamlı farklılık görülmedi. Ailedeki hemofili şiddeti ile faktör düzeyleri arasında istatiksel olarak anlamlı farklılık bulunmadı (p:0,398,). Ailedeki hemofili şiddeti ile spontan burun kanaması dışında kanamaya yatkınlık saptanmamıştır. Sonuç olarak; Hemofili hastalarının kız kardeşlerinde faktör düzeyleri daha düşük ve kontrol grubuna göre daha fazla küçük yaralanmalar sonrası uzamış kanama, artmış yaralanma sıklığı, diş çekimi sonrası uzamış kanama nedeni ile ilave tedavi gereksinimi, uzamış menstural periyod kanaması ve doğum sonrası uzamış kanamaları olmaktadır. Bu nedenle zorunlu ve olası taşıyıcılarda faktör düzeylerinin belirlenmesi medikal işlemler ve uzamış kanamalar açısından önemlidir. Anahtar sözcükler; Hemofili, hemofili hastalarının kız kardeşleri, pıhtılaşma faktörleri, kanama eğilimi, ailedeki hemofili şiddeti
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    Öğe
    Is fat mass more effective than body mass index (BMI) to predict toxicity in early breast cancer patients treated with doxorubicin and cyclophosphamide?
    (Amer Assoc Cancer Research, 2018) Kaplan, Muhammet Ali; Kavak, Hemrin; Urakci, Zuhat; Nas, Necip; Oruc, Zeynep; Yerlikaya, Halis; Akdeniz, Nadiye
    [Abstract Not Available]
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    Öğe
    KRAS codon 12 and 13 mutations may guide the selection of irinotecan or oxaliplatin in first-line treatment of metastatic colorectal cancer
    (Taylor & Francis As, 2019) Ergun, Yakup; Acikgoz, Yusuf; Bal, Oznur; Ucar, Gokhan; Dirikoc, Merve; Yildirim, Eda Caliskan; Akdeniz, Nadiye
    Background: In this study, we aimed to investigate the frequency, prognostic effect of codon, and amino acid-specific KRAS mutations in patients with metastatic colorectal cancer (mCRC) and their predictive effect on irinotecan and oxaliplatin during first-line treatment. Methods: The data of 304 mCRC patients were retrospectively evaluated between 2010 and 2018. Patients were categorized according to the most prominent codon and amino acid mutation and their prognostic features were analyzed. Results: In total, 274 patients were included in the study and 128 patients (47%) revealed KRAS mutation. Median follow-up time was 19.8 months (range; 1.6-96). The median overall survival rates for patients with codons 12 and 13 mutations were 25.4 and 22.2 months, respectively (p = 0.4). Moreover, the median overall survival for the codon 12 mutant patients who received irinotecan-based chemotherapy in the first-line treatment was 42.7 months, whereas for the codon 13 mutant and KRAS wild-type patients, it was 18.3 and 23.9 months, respectively (codon 12 vs. codon 13; HR: 0.31, p = 0.03, codon 12 vs. wild-type; HR: 0.45, p = 0.03). Conclusion: The significant survival advantage was observed in patients with codon 12 mutations who received irinotecan-based chemotherapy as a first-line treatment.
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    Öğe
    Meme kanserinde Brca-1 ve Brca-2’de sık görülen polimorfizm mutasyonların bölgemizde varlığı
    (Dicle Üniversitesi Tıp Fakültesi, 2019) Akkuzu, Mustafa Zanyar; Küçüköner, Mehmet; İrtegün, Sevgi; Urakçı, Zuhat; Kaplan, Muhammet Ali; Büyükbayram, Hüseyin; Işıkdoğan, Abdurrahman; Akdeniz, Nadiye
    Amaç: Meme kanseri kadınlar arasında en sık görülen ve en fazla ölüme neden olan kanser tipidir. Meme kanseri oluşumunda birçok tümör supresör gen, onkogen ve DNA tamir genleri rol oynamaktadır. Tümör supresör genlerden BRCA-1-2 meme kanserine yol açtığı bilinen genlerdir. Bu çalışmada ülkemizde başka bölgelerde yapılmış olan BRCA1-2 genlerinde ki sık görülen polimorfizm mutasyonların kendi bölgemizdeki sıklığı araştırıldı. Araştırmamızda Dicle Üniversitesi Onkoloji Bilim Dalında meme kanseri tanısı almış genç yaş (44 yaş altı) grubu 96 hastanın tümör dokusundan çalışıldı. BRCA-1 (rs16942, rs1799966) ve BRCA-2 (rs144848, rs1799944) genlerine ait polimorfik mutasyonları PCR özgül belirleme grubundan Hibridizasyon Prob Yöntemiyle “LightCycler” PCR cihazı kullanılarak belirlemeyi amaçladık. Bulgular: Çalışma hastalarının BRCA-1 genine ait rs16942’de 14 (%14,5) adet homozigot (GG), 55 (%57,3) adet heterozigot (AG) ; rs1799966’ da 18 (%18,7) adet homozigot (GG), 46 (%47,9) adet heterozigot (AG); BRCA-2 genine ait rs144848’ de 9 (%9,37) adet homozigot (TT), 25 (%26,04) adet heterozigot (GT); rs1799944’ de de 2 (%2,08) adet homozigot (GG), 3 (%3,12) adet heterozigot (AG) hastada polimorfik gen mutasyonları saptadık. Bu mutasyonların hastalık yaş grubu, evre, grade, ER pozitifliği ve HER-2 pozitifliği ile ilişkili olmadığını saptadık. Yaş ile mutasyon sıklığı bakıldığında 35 yaş altında, evre 2 ve evre 3’ de, grade 2 ve grade 3’de mutasyon oranları numerik olarak artmakla beraber p değerinin klinik bir anlamlılık yoktu. Sonuç: Bölgemiz açısından BRCA-1-2 polimorfizm mutasyonları önemli oranda olup hasta bireylerin ve ailelerin taranması önemlidir. BRCA-1/BRCA-2 deki bu polimorfizm mutasyonlarının yaş, evre, grade, ER durumu, HER durumu ile ilişkisinin olmadığını saptadık.
  • Küçük Resim
    Öğe
    Neoadjuvan kemoterapi alan luminal tip meme kanserli hastalarda patolojik tam yanıtı predikte eden faktörler
    (Dicle Üniversitesi Tıp Fakültesi, 2023) Urakçı, Zuhat; Akdeniz, Nadiye; Tunç, Sezai; Oruç, Zeynep; Küçüköner, Mehmet; Kaplan, Muhammet Ali; Büyükbayram, Hüseyin; Işıkdoğan, Abdurrahman
    Amaç: Luminal tip meme kanserinde birçok çalışma yapılmış olmasına rağmen günümüzde bu tip meme kanserinde patolojik tam yanıtı (pCR) predikte eden faktörler halen net olarak bilinmemektedir. Bu çalışmamızda neoadjuvan kemoterapi alan luminal tip meme kanserli hastalarda patolojik tam yanıtı predikte eden faktörleri incelemeyi amaçladık. Yöntemler: Çalışmaya Ocak 2010 ile Aralık 2018 arasında onkoloji merkezimizde neoadjuvan kemoterapi alan, luminal tip lokal ve lokal ileri evre meme kanserli, 18 yaşından büyük, 122 kadın hasta dahil edildi. Çalışmamızda neoadjuvan kemoterapi alan luminal tip meme kanseri tanılı hastalarda patolojik tam yanıtı predikte etme potansiyeli olan faktörleri retrospektif olarak inceledik. Bulgular: Hastaların menopozal durumu (p=0.638), tümör lokalizasyonu (sağ-sol) (p=0.791) ve tümör boyutu (p=0.861) ile pCR arasında istatistiksel olarak anlamlı ilişki izlenmedi. Patolojik tam yanıt ile invaziv duktal karsinom histolojisine sahip olma (p=0.001), östrojen reseptör (ER) negatifliği (p=0.034), insan epidermal büyüme faktörü reseptör-2 pozitifliği (HER2) (p=0.030) ve nod negatifliği (p=0.023) arasında istatistiksel olarak anlamlı ilişki saptandı. Patolojik tam yanıt ile hastalığın evresi (II-III) (p=0.051) ve Ki-67 düzeyi (<%20/ ≥%20) (p=0.060) arasında sınırda istatistiksel anlamlılık mevcuttu. Regresyon analizinde, diğer potansiyel prognostik faktörler ile birlikte değerlendirildiğinde, nod negatifliği ve ER negatifliği pCR’ı predikte eden bağımsız faktörler olarak saptandı (p=0.008, p=0.040, sırası ile). Patolojik tam yanıt elde edilen hasta grubuyla pCR sağlanamayan grup arasında hem hastalıksız sağkalım (DFS) hem de genel sağkalım (OS) açısından farklılık izlenmedi (p=0.315, p=0.576 sırası ile). Sonuç: Çalışmamızda ER negatifliği ve nod negatifliği pCR’ı predikte eden bağımsız faktörler olarak saptandı. Ki-67’nin %20 üzerinde olması pCR açısından sınırda anlamlılık göstermekteydi. Luminal tip meme kanserli hasta grubunda patolojik tam yanıt prognostik bir faktör olarak saptanmadı.
  • Küçük Resim
    Öğe
    Prognostic importance of primary tumor location in RAS mutant metastatic colorectal cancer
    (Dicle Üniversitesi Tıp Fakültesi, 2019) Akdeniz, Nadiye; Kaplan, Muhammet Ali; Küçüköner, Mehmet; Urakçı, Zuhat; Sezgin, Yasin; Ebinç, Senar; Bilen, Erkan; Karhan, Oğur; Laçin, Şahin; Büyükbayram, Hüseyin; Işıkdoğan, Abdurrahman
    Objective: The prognostic value of tumor location in patients with metastatic colorectal cancer (mCRC) was reported by recent analyses in RAS wild-type patients. However, there is no enough specific data regarding prognostic value of primary tumor location in RAS mutated mCRC patients. We aimed to find if there is any relation between tumor prognosis and primary tumor location in patients with RAS mutated mCRC. Method: This retrospective study included 57 patients with mCRC who were diagnosed and treated in our hospital between January 2011 and December 2017. Characteristics features of the patients were obtained from our institution patient medical records. Patients were included to the present study if KRAS or NRAS mutation was detected in tumor tissues.Results: Twenty-nine (50.9%) of patients were female and the median age of all patients was 52 (18-80) years. Forty (70.2%) of 57 patients were defined as left side (LS) and 17 (29.8%) of patients were located in the right side (RS). As first line systemic treatment, twenty-five (43.9%) patients had received oxaliplatin-based chemotherapy while 32 (56.1%) patients had received irinotecan-based chemotherapy. Tumor sidedness did not affect on progression-free survival (PFS) (mPFS, 10.9 months for LS vs 8.1 months for RS, p=0.400) and overall survival (OS) (mOS, 20.9 months for LS vs 20.8 months for RS, p=0.930).The patients who had oxaliplatin based chemotherapy regimens showed better OS rate than irinotecan based regimens (28.7months vs16.3 months, p=0.017, respectively). Conclusion: Our study results support the thought that claims the sidedness of primary CRC in metastatic setting does not have effect on PFS and OS in patients with RAS mutant mCRC. However, our findings also underline the necessity of studies with larger patient populations and subgroup analyzes to evaluate potential prognostic and molecular features to determine the standart approach to this specific subgroup of the disease.
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    Öğe
    Prognostic importance of tumor location and anti-EGFR therapy in patients with K-RAS wild type metastatic colorectal cancer
    (Imprimatur Publications, 2019) Kucukoner, Mehmet; Oztekin, Esen; Akdeniz, Nadiye; Morkuzu, Suat; Yerlikaya, Halts; Urakci, Zuhat; Kaplan, Muhammed Ali
    Purpose: To compare anti-EGFR and anti-VEGF agents in patients with K-RAS wild-type metastatic colorectal cancer (mCRC) with regards to tumor location. Methods: 450 patients diagnosed with mCRC, who applied to our center were included in this retrospective study. Of 450 patients, 303 underwent K-RAS mutation tests, assessed as having right-sided or left-sided mCRC and grouped according to localization of right and left colon. Sixty-five patients with K-RAS wild-type mCRC, who were treated with first-line anti-EGFR or anti-VEGF containing combination therapies of fluorouracil with leucovorin and either irinotecan or oxaliplatin were compared. Results: 393 (87%) out of 450 mCRC patients had left-sided colon cancers, and 57(13%) had right-side colon cancers. K-RAS analysis was performed in 303 of 450 patients with mCRC, 186 (61.4%) patients had K-RAS wild-type and 117 (38.6%) had K-RAS mutant. Median survival for right-sided cancers was 23.3 months and 29.4 months for left-sided cancers (p=0.309). Median progression-free survival (PFS) was 10.4 months (95% CI 7.3-13.4) in the anti-EGFR containing regimens group and 9.7 months (8.2-11.1) in the anti-VEGF containing regimens group (p=0.037); however, median overall survival (OS) was 18.4 months (95% CI 11.7-25.1) in the anti-EGFR containing regimens group and 19.3 months (95% CI 15.7-22.9) in the anti-VEGF containing regimens group (p=0.635). Conclusion: Addition of anti-EGFR in left sided K-RAS wild-type mCRC regarding PFS was beneficial, however there was no difference in terms of OS.
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    The prognostic role of baseline 18F-FDG PET/CT SUVmax and SUVmax change in patients with node-positive breast cancer receiving neoadjuvant chemotherapy
    (Ediciones Doyma, S.L., 2022) Can, Canan; Akdeniz, Nadiye; Kömek, Halil; Gündogan, Cihan; Urakçı, Zuhat; Işıkdoǧan, Abdurrahman
    Objective: This study aimed to determine the prognostic role of baseline maximum standardized uptake value (SUVmax) obtained by pretreatment PET/CT and the change in SUVmax (?SUVmax [%]) in patients with axillary lymph node–positive breast cancer receiving neoadjuvant chemotherapy (NAC). Methods: One hundred and eighty patients with baseline SUVmax and 121 patients with SUVmax measurement after treatment were evaluated in the study. The baseline SUVmax value of the breast (SUVmaxBI) and axilla (SUVmaxAI) and the change in the SUVmax of the breast (?SUVmaxB) and axilla (?SUVmaxA) were measured. The optimal cut-off value of SUVmax and ?SUVmax were determined by ROC curve analysis. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan–Meier curves. Results: ?SUVmaxB, pCRB, pCRA, and pCR parameters were found to be associated with relapse (p < 0.001, p = 0.033, p = 0.016, and p = 0.013, respectively). ?SUVmaxB and SUVmaxAI were associated with mortality (p = 0.001 and p = 0.006, respectively). Multiple Cox regression analyses revealed that ?SUVmaxB value was an independent prognostic factor for relapse and mortality (p = 0.013 and p = 0.010, respectively). Conclusion: The results showed that ?SUVmaxB was an independent prognostic factor for relapse and mortality in patients with axillary lymph node–positive breast cancer who received NAC.
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    The prognostic role of baseline F-18-FDG PET/CT SUVmax and SUVmax change in patients with node-positive breast cancer receiving neoadjuvant chemotherapy
    (Elsevier Espana SLU, 2022) Can, Canan; Akdeniz, Nadiye; Kömek, Halil; Gündoğan, Cihan; Urakçı, Zuhat; Işıkdogan, Abdurrahman
    Objective: This study aimed to determine the prognostic role of baseline maximum standardized uptake value (SUVmax) obtained by pretreatment PET/CT and the change in SUVmax ( ASUVmax [90]) in patients with axillary lymph node -positive breast cancer receiving neoadjuvant chemotherapy (NAC). Methods: One hundred and eighty patients with baseline SUVmax and 121 patients with SUVmax measurement after treatment were evaluated in the study. The baseline SUVmax value of the breast (SUVmaxBI) and axilla (SUVmaxAl) and the change in the SUVmax of the breast (ASUVmaxp,) and axilla (ASUVmaxA) were measured. The optimal cut-off value of SUVmax and ASUVmax were determined by ROC curve analysis. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan -Meier curves. Results: \SUVmax5, pCRB, pCRA, and pCR parameters were found to be associated with relapse (P<.001, P=.033, P=.016, and P=.013, respectively). ASUVmaxB and SUVmaxAl were associated with mortality (P=.001 and P=.006, respectively). Multiple Cox regression analyses revealed that \SUVmax5 value was an independent prognostic factor for relapse and mortality (P=.013 and P=.010, respectively). Conclusion: The results showed that ASUVmax5 was an independent prognostic factor for relapse and mortality in patients with axillary lymph node -positive breast cancer who received NAC. 0 2021 Sociedad Espanola de Medicina Nuclear e lmagen Molecular. Published by Elsevier Espana, S.L.U. All rights reserved.
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    Prognostic value of lymph node and spleen activity in [18F]FDG PET-CT in lung adenocarcinoma and squamous cell carcinoma
    (Dicle Üniversitesi Tıp Fakültesi, 2019) Kömek, Halil; Akdeniz, Nadiye; Urakçı, Zuhat; Can, Canan; Altındağ, Serdar
    Objective: We aimed to investigate the prognostic value of primary mass, spleen and lymph node metabolic activity in [18F]FDG PET-CT as well as the prognostic value of neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (TLR) in patients with lung adenocarcinoma and squamous cell carcinoma. Methods: Seventy-four patients, with pathological data, complete blood count and [18F]FDG PET-CT images, were retrospectively evaluated. Patients were grouped as lung adenocarcinoma (n = 32) or squamous cell carcinoma (n = 42). The time between [18F]FDG PET-CT imaging and death was calculated. Standardized uptake value (SUVmax) of primary lesion was calculated (lung or mediastinum). The SUVmax value of the spleen was used as an indicator of RES activity. Metabolic activity of lymph node was calculated from the lymph node having the highest activity independent of localization. Results: The SUVmax spleen/liver and SUVmax lymph node/liver ratios were significantly higher in the exitus subgroup of squamous cell carcinoma (p=0.025, p=0.043; respectively). The SUVmax lymph node/liver ratio was found to be a predictor for survival in squamous cell carcinoma (p=0.019, OR:1.282). The SUVmax spleen/liver and SUVmax lymph node/liver ratios were similar between subgroups of adenocancer. Conclusions: The SUV ratios of the spleen were not a predictor for survival in both groups. The SUVmax lymph node/liver ratio was found to be a predictor for survival in squamous cell carcinoma. However, NLR and PLR were not found to be prognostic factors.
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    Rare Breast Cancer Types: A Study About Characteristics, Outcomes, and Peculiarities
    (2020) Kaplan, Muhammet Ali; Karhan, Oğur; Urakçı, Zuhat; Ebınc, Senar; Akdeniz, Nadiye; Sezgin, Yasin; Nacir, Mustafa
    Objective: We aimed to explore different features of rarely seen breast cancer (BC) subtypes, including their stage, molecularsubtypes, treatment choices, and prognosis. Material and Methods: We retrospectively screened patients who were diagnosed with BC inour hospital between July 2010 and June 2018. A total of 97 patients who had micropapillary, cribriform, mucinous, papillary, tubular, apocrine, metaplastic, medullary, and myoepithelial subtypes of BC were finally included in the current study.Results: Ninety-four (96.9%) patients were females. Patients with cribriform and mucinous subtypes were in the younger median age of 41 and 45 years, respectively, whereaspapillary cases were reported in the oldest median age (64.5 years). Lymph node and TNM stages showed a statistical difference between thesubtypes (p=0.029 and p=0.008, respectively). Most of the cribriform (60%), metaplastic (66.7%), and papillary (70%) cases were diagnosedwithout lymph node involvement. Apocrine (79%) and micropapillary (75%) tumors mostly presented with nodal involvement. Whilemedullary (75%), tubular (66.7%), and cribriform (66.7%) carcinomas were more likely to be diagnosed at stage II, micropapillary (70.8%),and apocrine (62.5%) carcinomas were mostly diagnosed at stage III. Mucinous, tubular, and cribriform tumors were noticed in the luminalgroup. Medullary, metaplastic, apocrine, and papillary tumors included triple-negative subgroups. HER2-enriched tumors included apocrine(62.5%), medullary (50%), and micropapillary (25%) subtypes. Disease-free survival and overall survival of the patients showed marginal statistical significance according to tumor subtypes (p=0.086, p=0.085, respectively). Conclusion: In this study, we investigated important features, clinical behavior, management, and outcomes of several rare BC subtypes. We opine that the current study may prove instrumental andinformative for both daily clinical practice and future studies.
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    Rare occurrence of synovial sarcoma originating from dura mater
    (Istanbul Tip Fakultesi, 2019) Akdeniz, Nadiye; Küçüköner, Mehmet; Kaplan, Muhammet Ali; Urakçı, Zuhat; Yerlikaya, Halis; Karhan, Oğur; Teke, Fatma; Işıkdoğan, Abdurrahman
    Primary or metastatic dura mater sarcomas are rarely seen, and dural synovial sarcomas are quite rare. Here we report the case of a 60-year-old man who presented with headache, nausea, and vomiting and was found to have a 63×33×40-mm mass with solid and cystic components in parieto-occipital lobe. The mass was resected completely, with no residue detected on postoperative magnetic resonance imagining. On pathological evaluation, a vimentin-, S100-, transducer-like enhancer of split 1-, BCL-2-, and EMApositive and desmin-, PR-, CD99-, PANCK-, and GFAP-negative synovial sarcoma with Ki-67 proliferation index of 12% was detected. Postoperatively, chemotherapy has been started, and it will be followed by radiotherapy. Primary meningeal-derived sarcomas are rare, and differential diagnosis with other meningeal mesenchymal tumors is based on the findings of morphological and immunohistochemical analyses.
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    The role of basal 18F-FDG PET/CT maximum standard uptake value and maximum standard uptake change in predicting pathological response in breast cancer patients receiving neoadjuvant chemotherapy
    (Lippincott William & Wilkins, 2021) Akdeniz, Nadiye; Kömek, Halil; Küçüköner, Mehmet; Kaplan, Muhammet A.; Urakçı, Zuhat; Oruç, Zeynep; Işıkdoğan, Abdurrahman
    Objective The aim of this study was to determine the role of 18F-FDG PET/CT in predicting pathological response among patients diagnosed with local or locally advanced breast cancer and receiving neoadjuvant chemotherapy (NAC). Methods Basal SUVmax value were analyzed in 212 patients and 142 of these patients had posttreatment SUVmax value. Overall pathological complete response (pCR(C)) was defined as no evidence of residual invasive cancer in breast (pCR(B)) and axilla (pCR(A)). Basal SUVmax value of the breast (SUVmax(B)I) and axilla (SUVmax(A)I) and change in SUVmax of the breast (Delta SUVmax(B)) and axilla (Delta SUVmax(A)) were measured. The optimal cutoff value of SUVmax and Delta SUVmax were determined by receiver operating characteristic curve analysis. Results The number of patients with pCR(B) was 85 (40.1%), pCR(A) was 76 (42.5%) and pCR(C) was 70 (33%). In the artificial neural network-based analysis the Delta SUVmax(B) (100%) was the most important variable for predicting pCR(B). Delta SUVmax(A) (100%) was the most important variable in estimation of pCR(A). When pCR(C) was evaluated, the highest relation was found with Delta SUVmax(B). When the Delta SUVmax(B) cutoff value for pCR(B) and pCR(C) accepted as <=-87.9%, its sensitivity was 82.3 and 82.4%, and specificity was 72.5% and 65.9%, respectively (P < 0.001 and P < 0.001, respectively). When the Delta SUVmax(A) cutoff value for pCR(A) and pCR(C) accepted as <=-86.6%, its sensitivity was 94.3% and 97.6%, and specificity was 31.3% and 28.2%, respectively (P = 0.017 and P = 0.024, respectively). Conclusion Albeit varies according to the molecular subtypes of the breast cancer during NAC, Delta SUVmax value seems to be the most strong factor associated with pCR.
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    Role of volumetric parameters obtained from 68 Ga-PSMA PET/CT and 18F-FDG PET/CT in predicting overall survival in patients with mCRPC receiving taxane therapy
    (Springer, 2023) Guzel, Yunus; Komek, Halil; Can, Canan; Kaplan, Ihsan; Akdeniz, Nadiye; Kepenek, Ferat; Gundogan, Cihan
    ObjectiveThe aim of this study was to determine the prognostic role of volumetric parameters and Pro-PET scores obtained from (68) Ga-prostate-specific membrane antigen (PSMA) PET/CT and F-18-FDG PET/CT in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving taxane therapy.Materials and methodsThe study included 71 patients who underwent simultaneous PSMA and F-18-FDG PET/CT imaging between January 2019 and January 2022, had a Pro-PET score of 3-5 and had received taxane therapy after imaging. F-18-FDG tumor volume (TV-F) and PSMA tumor volume (TV-P) values of the lesions and total lesion glycolysis (TL-G) and total lesion PSMA (TL-P) values of the lesions were calculated on both imaging studies and the effects of these parameters on overall survival (OS) were investigated.ResultsThe median age of the patients included herein was 71 years (56-89) and the median prostate-specific antigen (PSA) level was 16.4 (0.01-1852 ng/dL). According to the Kaplan-Meier survival analysis, TTV-P >= 78.5, TTL-P >= 278.8, TTV-F >= 94.98, TTL-G >= 458.3, TTV-P + F >= 195.45, TTL-G + P >= 855.78, lymph node (L)TV-FDG >= 3.4, LFDG-SUVmax >= 3.2, LFDG-SUVmean >= 2.25, LFDG-SUVpeak >= 2.55, and bone (B)TV-F >= 51.15 values were found to be prognostic factors in predicting short OS. Multivariate Cox regression analysis showed that a Vscore >= 3 (95% confidence interval [CI]: 7.069-98.251, p < 0.001) and TTL-G + P >= 855.78 (95% CI: 4.878-1037.860, p = 0.006) were found to be independent prognostic factors in predicting short OS.ConclusionVolumetric parameters and Pro-PET scores obtained from (68) Ga-PSMA PET/CT and F-18-FDG PET/CT imaging have been shown to have an impact on OS in patients with mCRPC receiving taxane therapy.
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    Sunitinib or pazopanib: Is there any difference between tyrosine kinase inhibitors in the pre-nivolumab setting in metastatic renal cell carcinoma?
    (Cureus Inc., 2020) Uçar, Gökhan; Açıkgöz, Yusuf; Ergun, Yakup; Bal, Öznur; Yılmaz, Mesut; Karakaya, Serdar; Akdeniz, Nadiye; Köstek, Osman; Isak, Özlem Aydın; Şener, Görkem Yazıcı; Dirikoç, Merve; Esen, Selin Aktürk; Doğan, Mutlu; Uncu, Doğan
    Introduction Treatment options for metastatic renal cell carcinoma disease have been improved in recent years. However, there is still no optimal treatment sequence or combination for metastatic disease. We aimed to investigate whether patients differed in terms of disease outcomes regarding pre-nivolumab tyrosine kinase inhibitors (TKIs). Material and methods The analysis of patients was performed after all cohorts were sub-grouped into two groups according to pre-nivolumab TKIs as following the sunitinib arm and the pazopanib arm. Result A total of 75 patients were included in this study. The median follow-up time was eight months for all cohorts. The objective response rate was statistically significantly higher in the pazopanib arm as compared to the sunitinib arm (56% vs 30%, p=0.02). Progression-free survival was significantly higher in pazopanib than sunitinib (10.3 months vs 5.3 months, p=0.02). Multivariate analysis revealed that pazopanib treatment was associated with better progression-free survival (HR: 0.44, 95 CI; 0.22-0.91, p=0.02). While the median overall survival for patients who had received sunitinib was 11.0 months, it has not been reached the median in the pazopanib arm (11.0 months vs NR, p=0.051). Discussion We demonstrated significantly better progression-free survival and a higher objective response rate with nivolumab treatment in patients who had received pazopanib as compared with patients who received sunitinib in the pre-nivolumab period.