Publication: Metastatik kolorektal kanserinde kemoterapi öncesi timidin kinaz aktivite düzeylerinin prognostik önemi
Abstract
Giriş ve amaç: Serum timidin kinaz 1 (TK1) tümör hücre proliferasyonunun duyarlı bir belirtecidir. Hematolojik ve erken evre solid organ tümörlerinde tedaviye yanıtı ve hastalıksız sağkalımı tahmin etmede kullanılabileceği bildirilmiştir ancak TK1 aktivite düzeyini metastatik solid organ tümörlerinde prognostik bir risk faktörü olarak inceleyen fazla sayıda çalışma yoktur. Bu çalışmada palyatif kemoterapi alan metastatik kolorektal kanserli (MKRK) hastalarda serum TK aktivite düzeylerinin prognostik öneminin araştırılması amaçlandı. Gereç ve yöntem: Çalışmamızda hastanemiz medikal onkoloji polikliniklerine başvuran ardışık 46 metastatik MKRK’ li hastanın tedavi öncesi ve 2. Kür öncesi serum TK1 aktivite düzeyleri yüksek duyarlılığa sahip radyoaktif olmayan DiviTum kitleri kullanılarak ölçüldü. Kontrol grubu olarak 10 sağlıklı gönüllü alındı. Serum TK1 aktivite düzeyi, performans statüsü, yaş,cinsiyet, kilo kaybı, hematolojik ve biyolojik parametreler, serum CEA ve CA 19.9 düzeyleri ile sağkalım süresi arasında ki ilişkileri incelendi. Bulgular: Çalışma grubu ile sağlıklı gönüllülerin serum TK1 aktivite düzeyleri karşılaştırıldığında hasta grubunun serum TK1 aktivite düzeyleri anlamlı olarak yüksek saptandı (sırasıyla 162.1± 27.8 vs 32.97±7.307; p<0.03). Çok değişkenli analizde serum TK1 düzeyleri ve kemoterapi öncesi kilo kaybı; bağımsız prognostik risk faktörleri olarak saptandılar (sırası ile p=0.001 ; 0.018). ROC eğrisi analizi ile TK1 aktivite düzeyinin kestirim değeri progresyonsuz sağkalım (PSK) ve genel sağkalım (GSK) için sırası ile 65 ve 230 Du/ L olarak saptandı. TK1 aktivite düzeyi 65 Du/ L’nin altında olan hasta grubunun PSK anlamlı olarak uzun saptandı (624 vs 231 gün; p <0.0001). TK1 aktivite düzeyi 230 Du/ L'nin üzerinde olan hasta grubunun genel sağkalım süresi anlamlı olarak daha kısa idi (p<0.0001) .Kemoterapi öncesi ve 1.kür sonrası bakılan serum TK1 aktivite düzeyleri kemoterapi öncesi bakılan değerlerden anlamlı olarak yüksek saptandı(p< 0.36) ancak farkın büyüklüğü ile sağkalım arasında anlamlı bir ilişki saptanamadı (p=0.6). Sonuç: Bu çalışmada kemoterapi öncesi yüksek TK1 aktivite düzeyinin MKRK’de sağkalımla anlamlı olarak ilişkili olduğu gösterilmiştir. Elde ettiğimiz sonuçlar serum TK1 aktivite tayininin metastatik solid tümörlerde prognozu tahmin eden bağımsız bir marker olma özelliğinin doğrulanması yolunda yeni bir adım olarak kabul edilebilir. Anahtar sözcükler: Metastatik kolorektal kanser, kemoterapi, timidin kinaz, progresyonsuz sağkalım, genel sağkalım
Aim and background: Serum thymidine kinase 1 (TK1) is a sensitive marker of tumor cell proliferation. It has been reported as a predictive factor for response rate and disease free survival for hematological and early stage solid organ tumors but its importance as a prognostic factor in metastatic solid organ malignancies is not well studied. In this study we aimed to investigate the prognostic significance of serum TK1 activity in metastatic colorectal cancer (MCRC) patients receiving palliative chemotherapy. Method: We prospectively measured serum TK1 activity immediately before the first and second cycle of the treatment in 46 consecutive metastatic MCRC patients. 10 healthy volunteers were also included as a control group. TK1 activity was measured by means of high sensitive non-radioactive DIVITUM assay. The patients’ performance status, age, gender, weight loss, hematological and biochemical parameters, serum CEA and CA 19.9 levels and serum TK1 activity levels relation with survival were analyzed. Results: The mean TK1 level in the study group was significantly higher than the controls (162.1± 27.8 vs 32.97±7.307; p<0.03, respectively). In multivariate analysis adjusted for known clinicopathological risk factors, serum tumor markers, hemoglobin levels and trombosit count TK1 levels before chemotherapy and weight loss remained as independent prognostic factors ( p=0.001; 0.018, respectively). Patients with TK1 activity level above 65 Du/ L and 230 Du/ L had a longer PFS (624 vs. 231 days) and OS time respectively (p <0.0001 for each cut off value). Although the mean TK1 levels before second cycle of chemotherapy was higher than baseline TK1 levels significantly no significant relationship between the magnitude of difference and survival time was detected (p=0.6). Conclusion: In this study we demonstrated that in the setting of MCRC a significant relation between TK1 levels and survival exists. We consider our results a step further for validation of serum TK1 activity level as an independent prognostic factor in metastatic solid organ tumors. Key words: metastatic colorectal cancer, chemotherapy, progression free survival, overall survival, thymidine kinase.
Aim and background: Serum thymidine kinase 1 (TK1) is a sensitive marker of tumor cell proliferation. It has been reported as a predictive factor for response rate and disease free survival for hematological and early stage solid organ tumors but its importance as a prognostic factor in metastatic solid organ malignancies is not well studied. In this study we aimed to investigate the prognostic significance of serum TK1 activity in metastatic colorectal cancer (MCRC) patients receiving palliative chemotherapy. Method: We prospectively measured serum TK1 activity immediately before the first and second cycle of the treatment in 46 consecutive metastatic MCRC patients. 10 healthy volunteers were also included as a control group. TK1 activity was measured by means of high sensitive non-radioactive DIVITUM assay. The patients’ performance status, age, gender, weight loss, hematological and biochemical parameters, serum CEA and CA 19.9 levels and serum TK1 activity levels relation with survival were analyzed. Results: The mean TK1 level in the study group was significantly higher than the controls (162.1± 27.8 vs 32.97±7.307; p<0.03, respectively). In multivariate analysis adjusted for known clinicopathological risk factors, serum tumor markers, hemoglobin levels and trombosit count TK1 levels before chemotherapy and weight loss remained as independent prognostic factors ( p=0.001; 0.018, respectively). Patients with TK1 activity level above 65 Du/ L and 230 Du/ L had a longer PFS (624 vs. 231 days) and OS time respectively (p <0.0001 for each cut off value). Although the mean TK1 levels before second cycle of chemotherapy was higher than baseline TK1 levels significantly no significant relationship between the magnitude of difference and survival time was detected (p=0.6). Conclusion: In this study we demonstrated that in the setting of MCRC a significant relation between TK1 levels and survival exists. We consider our results a step further for validation of serum TK1 activity level as an independent prognostic factor in metastatic solid organ tumors. Key words: metastatic colorectal cancer, chemotherapy, progression free survival, overall survival, thymidine kinase.