Akciğer adenokarsinom nedeniyle cerrahi rezeksiyon yapılan hastalarda postoperatif adjuvan tedavi zamanlamasının sağ kalıma etkisi
The effect of postoperative adjuvant therapy timing on survival in patients undergoing surgical resection due to lung adenocarcinoma
Yazar: ALİ OSMAN TAŞ
Danışman: PROF. DR. OZAN YAZICI
Gazi Üniversitesi / Tıp Fakültesi / İç Hastalıkları Ana Bilim Dalı / Tıbbi Onkoloji Bilim Dalı
Derece: Tıpta Uzmanlık, 2024
Konu: İç Hastalıkları = Internal diseases

Özet:
Akciğer kanseri, dünya genelinde kanser insidansının ve mortalitesinin 
yaygın nedenlerinden biridir. Akciğer adenokarsinomu, çoğu ülkede akciğer 
kanserinin en yaygın histolojik alt tipidir ve tüm akciğer kanserlerinin yarısını 
oluşturmaktadır. Akciğer adenokarsinomu nüks potansiyeline sahip olup, bu 
tümörlerin doğru tanımlanması ve uygun adjuvan tedavinin seçilmesi postoperatif 
tedavi etkinliğini artıracaktır. Cerrahi, erken evre akciğer adenokarsinom tedavisi 
için birincil terapötik seçeneği oluşturur. Adjuvan kemoterapi erken evre küçük 
hücreli dışı akciğer karsinomu olan kötü prognozlu hastalarda sağ kalım üzerine 
önemli rol oynamaktadır. Adjuvan kemoterapi endikasyonları netleştirilmiş olsa da 
cerrahi rezeksiyondan sonraki uygun zamanlama tam olarak tanımlanmamıştır. 
Cerrahi rezeksiyon sonrası adjuvan kemoterapinin en uygun başlama zamanının 
belirlenmesi, hastaların tedaviye en iyi yanıtı vermelerini sağlamak ve nüks riskini 
azaltmak açısından kritik bir öneme sahiptir. Biz de bu çalışmada, akciğer kanseri 
nedeniyle opere edilen ve adjuvan tedavi alan hastaları değerlendirerek, adjuvan 
tedavi zamanının sağ kalım üzerine olan etkisini incelemeyi amaçladık. 

Gazi Üniversitesi Tıp Fakültesi İç Hastalıkları Medikal Onkoloji Bilim 
Dalı'nda son 10 yıl içerisinde 18 yaş ve üzeri, akciğer kanseri tanısı alan tüm 
hastalar değerlendirmeye alındı.  Histopatolojik tanısı küçük hücreli dışı akciğer 
karsinomu, Tümör-Nod-Metastaz (TNM) evrelemesine göre Evre I-II-IIIA olan, 
cerrahi geçirmiş ve sonrasında adjuvan kemoterapi veya kemo-radyoterapi alan 
hastalar seçildi. Hastaların demografik ve histopatolojik özellikleri, hastalıksız sağ 
kalım ve genel sağ kalım süreleri kaydedilerek adjuvan tedavi verilme sürelerinin 
bu parametreler ile ilişkisi incelendi. Adjuvan tedavi ve cerrahi arasında geçen 
sürenin sağ kalım sürelerine olan etkileri Kaplan-Meier testi ve log-rank testi ile 
değerlendirildi. Tek değişkenli analiz log-rank testi, çok değişkenli analiz için cox
regresyon modeli kullanıldı. Kategorik değişkenlerin değerlendirilmesinde Chi-Square testi uygulandı. İstatistiksel analizlerde p değerinin 0.05'ten küçük olması 
anlamlı olarak kabul edildi. 

Çalışmamızda histopatolojik bulgular ve adjuvan tedavi süresi ile 
hastalıksız sağ kalım arasındaki ilişki incelendiğinde patolojik lenf nodu 
değerlendirilmesi ve adjuvan tedaviye ilk 28 gün içerisinde başlanan hasta grupları 
arasında istatiksel olarak anlamlı ilişki saptandı.  Tek değişkenli analizde anlamlı 
çıkan bu iki parametre çok değişkenli analiz yapıldığında hem patolojik lenf nodu 
varlığının hem de adjuvan tedavi başlangıç süresinin prognostik olduğu saptandı 
(sırasıyla p = 0.07 ve p = 0.026). Aynı şekilde histopatolojik bulgular ve adjuvan 
tedavi süresi ile genel sağ kalım arasındaki ilişki incelendiğinde patolojik evre 
değerlendirmesi ile adjuvan tedaviye ilk 28 gün içerisinde başlanan hasta grupları 
arasında istatiksel olarak anlamlı ilişki saptandı. Tek değişkenli analizde istatiksel 
anlamlı olarak bulunan bu iki parametre ile çok değişkenli analiz yapıldığında hem 
patolojik evrede hem de adjuvan tedavi başlangıç süresinin prognostik olduğu 
saptandı (sırasıyla p = 0.020 ve p = 0.023). 

Sonuç olarak, çalışmamızda küçük hücreli dışı akciğer kanseri olan 
hastalara cerrahi sonrasında adjuvan kemoterapinin ilk 28 günlük süreçte 
verilmesinin hastalıksız sağ kalıma ve genel sağ kalıma olumlu etkisi olduğunu 
gösterdik. Çalışmamız adjuvan tedavinin zamanında başlatılmasının önemini 
vurgulamaktadır. Küçük hücreli dışı akciğer kanseri olan hastalarda erken tedavi 
verilmesinin prognoza etkisi ve cerrahiden kaynaklanan adjuvan tedavi 
gecikmesinin etkilerini açıklığa kavuşturmak için daha fazla sayıda hasta içeren 
araştırmaya ihtiyaç vardır.

Abstract:
Lung cancer is a prevalent cause of cancer incidence and mortality 
worldwide. Lung adenocarcinoma is the most common histological subtype of lung 
cancer in many countries, constituting half of all lung cancers. Lung 
adenocarcinoma has the potential for recurrence, and accurate identification of 
these tumors and the selection of appropriate adjuvant therapy will enhance 
postoperative treatment effectiveness. Surgery represents the primary therapeutic 
option for early-stage lung adenocarcinoma. Adjuvant chemotherapy plays a 
significant role in improving survival in patients with poorly prognostic early-stage 
non-small cell lung carcinoma. Although the indications for adjuvant chemotherapy 
have been clarified, the optimal timing after surgical resection has not been 
precisely defined. Determining the most appropriate timing for starting adjuvant 
chemotherapy after surgical resection is critical for ensuring the best response to 
treatment and reducing the risk of recurrence. 
In this study, we aimed to evaluate the impact of the timing of adjuvant 
treatment on survival by assessing patients who underwent surgery for lung cancer 
and received adjuvant therapy.All patients aged 18 and older diagnosed with lung 
cancer in the last 10 years in the Department of Medical Oncology, Faculty of 
Medicine, Gazi University were included in the study. Patients with non-small cell 
lung carcinoma, stages I-II-IIIA according to tumor-node-metastasis (TNM) 
staging, who underwent surgery and subsequently received adjuvant chemotherapy 
or chemo-radiotherapy, were selected. The demographic and histopathological 
characteristics of patients were recorded, and the relationship between the timing 
of adjuvant treatment and disease-free survival and overall survival was examined. 
The effects of the time between adjuvant treatment and surgery on survival were 
evaluated using the Kaplan-Meier test and log-rank test. The log-rank test was used 
for univariate analysis, and the Cox regression model was employed for 
x 
multivariate analysis. The Chi-Square test was applied for the evaluation of 
categorical variables. A p-value less than 0.05 was considered statistically 
significant. 
In our study, when the relationship between histopathological findings and 
the duration of adjuvant treatment and disease-free survival was examined, a 
statistically significant relationship was found between the assessment of 
pathological lymph nodes and patient groups starting adjuvant treatment within the 
first 28 days. This relationship remained significant in multivariate analysis for both 
the presence of pathological lymph nodes and the timing of adjuvant treatment (p 
= 0.07 and p = 0.026, respectively). Similarly, when the relationship between 
histopathological findings and the duration of adjuvant treatment and overall 
survival was examined, a statistically significant relationship was found between 
the evaluation of pathological stage and patient groups starting adjuvant treatment 
within the first 28 days. In multivariate analysis, both pathological stage and the 
timing of adjuvant treatment were found to be prognostic (p = 0.020 and p = 0.023, 
respectively). 
In conclusion, our study demonstrated a positive effect on disease-free 
survival and overall survival when adjuvant chemotherapy was administered within 
the first 28 days after surgery for non-small cell lung cancer. Our study emphasizes 
the importance of timely initiation of adjuvant treatment. Further research with a 
larger number of patients is needed to clarify the impact of early treatment in 
patients with non-small cell lung cancer and the effects of delays in adjuvant 
treatment due to surgery on prognosis.Lung cancer is a prevalent cause of cancer incidence and mortality 
worldwide. Lung adenocarcinoma is the most common histological subtype of lung 
cancer in many countries, constituting half of all lung cancers. Lung 
adenocarcinoma has the potential for recurrence, and accurate identification of 
these tumors and the selection of appropriate adjuvant therapy will enhance 
postoperative treatment effectiveness. Surgery represents the primary therapeutic 
option for early-stage lung adenocarcinoma. Adjuvant chemotherapy plays a 
significant role in improving survival in patients with poorly prognostic early-stage 
non-small cell lung carcinoma. Although the indications for adjuvant chemotherapy 
have been clarified, the optimal timing after surgical resection has not been 
precisely defined. Determining the most appropriate timing for starting adjuvant 
chemotherapy after surgical resection is critical for ensuring the best response to 
treatment and reducing the risk of recurrence. 
In this study, we aimed to evaluate the impact of the timing of adjuvant 
treatment on survival by assessing patients who underwent surgery for lung cancer 
and received adjuvant therapy.All patients aged 18 and older diagnosed with lung 
cancer in the last 10 years in the Department of Medical Oncology, Faculty of 
Medicine, Gazi University were included in the study. Patients with non-small cell 
lung carcinoma, stages I-II-IIIA according to tumor-node-metastasis (TNM) 
staging, who underwent surgery and subsequently received adjuvant chemotherapy 
or chemo-radiotherapy, were selected. The demographic and histopathological 
characteristics of patients were recorded, and the relationship between the timing 
of adjuvant treatment and disease-free survival and overall survival was examined. 
The effects of the time between adjuvant treatment and surgery on survival were 
evaluated using the Kaplan-Meier test and log-rank test. The log-rank test was used 
for univariate analysis, and the Cox regression model was employed for multivariate analysis. The Chi-Square test was applied for the evaluation of 
categorical variables. A p-value less than 0.05 was considered statistically 
significant. 
In our study, when the relationship between histopathological findings and 
the duration of adjuvant treatment and disease-free survival was examined, a 
statistically significant relationship was found between the assessment of 
pathological lymph nodes and patient groups starting adjuvant treatment within the 
first 28 days. This relationship remained significant in multivariate analysis for both 
the presence of pathological lymph nodes and the timing of adjuvant treatment (p 
= 0.07 and p = 0.026, respectively). Similarly, when the relationship between 
histopathological findings and the duration of adjuvant treatment and overall 
survival was examined, a statistically significant relationship was found between 
the evaluation of pathological stage and patient groups starting adjuvant treatment 
within the first 28 days. In multivariate analysis, both pathological stage and the 
timing of adjuvant treatment were found to be prognostic (p = 0.020 and p = 0.023, 
respectively). 
In conclusion, our study demonstrated a positive effect on disease-free 
survival and overall survival when adjuvant chemotherapy was administered within 
the first 28 days after surgery for non-small cell lung cancer. Our study emphasizes 
the importance of timely initiation of adjuvant treatment. Further research with a 
larger number of patients is needed to clarify the impact of early treatment in 
patients with non-small cell lung cancer and the effects of delays in adjuvant 
treatment due to surgery on prognosis.