İnopere serviks kanserli hastalarda küratif üç boyutlu konformal radyoterapi ve kemoradyoterapi sonuçları ve akut-kronik yan etkilerin retrospektif değerlendirilmesi
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Tarih
2019
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Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Merkezlerin kliniklerinde uyguladıkları tedavi protokollerinin sonuçlarının değerlendirilmesi tedavi kalitesinin arttırılmasını ve hastalara verilen hizmetin geliştirilmesini sağlayacaktır. Bu amaçla Ege Üniversitesi Tıp Fakültesi (EÜTF) Radyasyon Onkolojisi Anabilim Dalı'nda inoperabl serviks kanseri tanısı ile üç boyutlu konformal eksternal radyoterapi tekniği ile tedavi uygulanan olguların tedavi sonuçları, prognostik faktörler ve yan etki sonuçları ile yan etki gelişimi ile ilişkili olabilecek faktörler incelenmiştir. Gereç ve Yöntem: EÜTF Radyasyon Onkolojisi Anabilim Dalı'nda 2005-2015 yılları arasında küratif tedavi edilen ve üç boyutlu konformal radyoterapi uygulanan 274 hasta retrospektif olarak incelenmiş sağkalım analizleri için Kaplan Meier, sağkalım ile ilişkili prognostik faktörler için ise tek değişkenli analizde log-rank, çok değişkenli analizde cox regresyon testi uygulanmıştır. Yan etki gelişimi ile ilişkili olabilecek faktörler ki-kare testi ile incelenmiştir. Analizde p değeri < 0.05 olanlar anlamlı kabul edilmiştir. Bulgular: Çalışmamızda median takip süresi 62.3 ay (3-170) olup evre IIB çoğunluğunu (%63.9) oluşturmaktaydı. Olguların %91'i kemoradyoterapi (KRT) ile tedavi edilmiş, %86'sına brakiterapi yapılabilmiş, görüntü rehberliğinde brakiterapi (3B-BRT) 54 (%19.7), konvansiyonel brakiterapi (2B-BRT) 182 (%66.7) olguda uygulanmıştır. Serimizin 10 yıllık genel sağkalım, hastalıksız sağkalım, lokal-bölgesel kontrol ve uzak metastazsız sağkalım oranları sırasıyla %53, %62, %77 ve %72 olarak saptanmıştır. Hastalık yinelemesi görülen 90 olguda (%32) en sık yineleme paterni uzak metastazdır ve en sık uzak metastaz yeri paraaortik bölgedir. Çok değişkenli analizde tedaviye 3. ay yanıtı (p<0.0001) ve skuamoz hücreli karsinom dışı histopatoloji tüm sağkalımlarla ilişkili önemli prognostik faktörler olarak bulunmuştur. Lenf nodu metastazı sayısının ≥3 olması (p=0.042) ve üst pelvik yerleşimli (ana iliak) lenf nodu metastazının (p=0.025) uzak metastazsız sağkalım ile ilişkili olduğu gösterilmiştir. Radyoterapi öncesinde hemoglobin (Hb) düzeyinin <10 mg/dl olması genel sağkalım ve hastalıksız sağkalımı olumsuz etkilemektedir. Eş zamanlı kemoterapi (p<0.0001) ve ≥4 kür uygulanması genel sağkalımı arttırmaktadır (p<0.0001). En sık görülen derece ≥3 akut yan etki lökopenidir (%34). Hb düzeyi <10 mg/dl olması, eş zamanlı kemoterapi uygulanması derece ≥3 akut hematolojik yan etki gelişimi ile ilişkili bulunmuştur. Kronik genitoüriner (GÜS) ve gastrointestinal sistem (GİS) yan etkiler birlikte değerlendirildiğinde derece ≥3 yan etki %13 olguda izlenmiştir. Vücut kitle indeksinin (VKİ) < 18.5 olması kronik ciddi GÜS (p=0.001), brakiterapi dozunun 4x7 Gy olması kronik ciddi GİS (p=0.023) yan etki gelişimi ile ilişkili bulunmuştur. Brakiterapi tekniğinin (3B-BRT vs 2B-BRT) ciddi kronik yan etki gelişimi ile ilişkisi gösterilememiştir. Sadece 3B-BRT ile tedavi edilen olgular değerlendirildiğinde kronik derece 3-5 GÜS, GİS ve GİS+GÜS yan etkiler sırasıyla %5.7, %13.5 ve %20.8 bulunmuştur. Sonuç: Sağkalım sonuçlarımız literatür ile uyumlu olup uzak metastaz en sık görülen yineleme şeklidir ve tedavi başarısını etkilemektedir. Özellikle lenf nodu metastazı sayısı ve yerleşiminin paraaortik metastaz ve uzak metastaz gelişimi ile ilişkili olduğu bilinmekte, yüksek riskli olgularda profilaktik paraaortik ışınlamanın uzak metastazları azaltma üzerindeki etkisini araştıran randomize çalışmaların sonuçları beklenmektedir. Kronik yan etkiler açısından serimizin sonuçları diğer çalışmalarda belirtilen oranlarda olmasına karşın, 3B-BRT uygulanan olgular ayrı olarak incelendiğinde artmış derece ≥3 geç yan etki oranları izlenmiştir. Geç yan etki sonuçlarının dozimetrik verilerin de olduğu başka bir çalışma ile araştırılması uygun olacaktır.
Purpose: Evaluation of treatment protocol outcomes for individual centres leads to treat patients with better treatment quality and improve the services. For this aim clinical outcomes of three dimentional conformal curative intent radiotherapy for inoperabl cervical cancer, prognostic factors, side effects and also side effects releated risk factors have been evaluated for patients treated in Ege University School of Medicine (EUTF) Department of Radiation Oncology. Material-methods: Between 2005 and 2015, 274 patients diagnosed as inoperabl cervix cancer and treated in EUTF Department of Radiation Oncology Clinic with curative intent conformal radiotherapy were retrospectively evaluated. Kaplan Meier test was used for survival analysis and prognostic factors releated with survival results was calculated univariate analysis with log-rank test, mutlivariate analysis cox regression test. Ki-square test was used for analyses of side effects related factors. Results were considered istatistically significant when p value was less then 0,05. Results: The median follow up time was 62.3 months (3-170) and most of the patients were staged as IIB (63.9%). Patients treated with chemoradiotherapy and brachytherapy were respectively 91% and 86%, for those whom brachytherapy applied, brachytherapy technique with image guided was 54 (19.7%) and 182 (66.7%) with convantional. For our serial, 10 years overall survival, disease free survival, locoregional control and distant metastasis free survival rate were found respectively 53%, 62%, 77% and 72%. Disease recurrence was seen in 90 (32%) patients and distant metastasis was the most frequent recurrence patern and paraaortic region was the most frequent distant metastasis site. Multivariate analyses results showed that treatment response at 3rd month (p<0.0001) and non-squamous carcinoma histology were related with all survival types as prognostic factors. Pelvic metastatic lymph node number ≥3 (p=0.042) and common iliac lymph node metastasis (p=0.025) were associated with distant metastasis. The presence of initial (before radiotherapy) hemoglobin level <10 mg/dl effected overall survival and disease free survival poorly. Overall survival was improved with concurrent chemotherapy (p<0.0001) and ≥4 cycles was associated with better overall survival outcome (p<0.0001). The most frequent acute grade ≥3 side effect was leucopenia (34%). Acute grade ≥3 hematological side effect related factors were found as initial Hb level <10 mg/dl and concurrent chemoradiotherapy. When late genitourinary (GUS) and gastrointestinal (GIS) side effects evaluated together, grade ≥3 side effect rate was 13%. Body mass index <18.5 was associated with late severe genitourinary side effect (p=0.001) and bracyhtherapy dose applied as 4x7 Gy was related with severe gastrointestinal late side effect (p=0.023). Brachytherapy tecnique could not found as severe chronic side effect related factor. Conclusion: Our serial survival results were similar when compared with literature and most frequent recurrence pattern was distant metastases that effected treatment outcomes. Paraaortic metastasis related factors were known as number of lmyph node metastasis and common iliac location, and ongoing randomised study results are going to lead profilactic paraaortic irradiation for high risk patients to prevent distant metastasis. Severe chronic side effect rates were correlated with other serials, whereas subgroup of patients treated with 3D-BRT were found with increased severe late side effect when compared with other studies. This fact should be evaluated with another study which analyses dosimetric data and severe late side effects correlation.
Purpose: Evaluation of treatment protocol outcomes for individual centres leads to treat patients with better treatment quality and improve the services. For this aim clinical outcomes of three dimentional conformal curative intent radiotherapy for inoperabl cervical cancer, prognostic factors, side effects and also side effects releated risk factors have been evaluated for patients treated in Ege University School of Medicine (EUTF) Department of Radiation Oncology. Material-methods: Between 2005 and 2015, 274 patients diagnosed as inoperabl cervix cancer and treated in EUTF Department of Radiation Oncology Clinic with curative intent conformal radiotherapy were retrospectively evaluated. Kaplan Meier test was used for survival analysis and prognostic factors releated with survival results was calculated univariate analysis with log-rank test, mutlivariate analysis cox regression test. Ki-square test was used for analyses of side effects related factors. Results were considered istatistically significant when p value was less then 0,05. Results: The median follow up time was 62.3 months (3-170) and most of the patients were staged as IIB (63.9%). Patients treated with chemoradiotherapy and brachytherapy were respectively 91% and 86%, for those whom brachytherapy applied, brachytherapy technique with image guided was 54 (19.7%) and 182 (66.7%) with convantional. For our serial, 10 years overall survival, disease free survival, locoregional control and distant metastasis free survival rate were found respectively 53%, 62%, 77% and 72%. Disease recurrence was seen in 90 (32%) patients and distant metastasis was the most frequent recurrence patern and paraaortic region was the most frequent distant metastasis site. Multivariate analyses results showed that treatment response at 3rd month (p<0.0001) and non-squamous carcinoma histology were related with all survival types as prognostic factors. Pelvic metastatic lymph node number ≥3 (p=0.042) and common iliac lymph node metastasis (p=0.025) were associated with distant metastasis. The presence of initial (before radiotherapy) hemoglobin level <10 mg/dl effected overall survival and disease free survival poorly. Overall survival was improved with concurrent chemotherapy (p<0.0001) and ≥4 cycles was associated with better overall survival outcome (p<0.0001). The most frequent acute grade ≥3 side effect was leucopenia (34%). Acute grade ≥3 hematological side effect related factors were found as initial Hb level <10 mg/dl and concurrent chemoradiotherapy. When late genitourinary (GUS) and gastrointestinal (GIS) side effects evaluated together, grade ≥3 side effect rate was 13%. Body mass index <18.5 was associated with late severe genitourinary side effect (p=0.001) and bracyhtherapy dose applied as 4x7 Gy was related with severe gastrointestinal late side effect (p=0.023). Brachytherapy tecnique could not found as severe chronic side effect related factor. Conclusion: Our serial survival results were similar when compared with literature and most frequent recurrence pattern was distant metastases that effected treatment outcomes. Paraaortic metastasis related factors were known as number of lmyph node metastasis and common iliac location, and ongoing randomised study results are going to lead profilactic paraaortic irradiation for high risk patients to prevent distant metastasis. Severe chronic side effect rates were correlated with other serials, whereas subgroup of patients treated with 3D-BRT were found with increased severe late side effect when compared with other studies. This fact should be evaluated with another study which analyses dosimetric data and severe late side effects correlation.
Açıklama
Anahtar Kelimeler
İnopere Serviks Kanseri, Kemoradyoterapi, Yan Etki, Inoperabl Cervix Cancer, Chemoradiotherapy, Side Effect
