NEOADJUVAN KEMOTERAPİ SONRASI OPERE OLAN EVRE III AKCİĞER KANSERLİ HASTALARIN KLİNİK SONUÇLARI: KEMOTERAPİ REJİMİNİN ETKİSİ

Giriş: Neoadjuvan tedavi, küçük hücreli dışı akciğer kanseri (KHDAK) tedavisinde en tartışmalı konulardan birisidir. Bu çalışmada, neoadjuvan kemoterapiden sonra opere edilen evre III KHDAK'li hastaların, kemoterapi protokollerine göre uzun dönem klinik sonlanımlarının karşılaştırılmasını amaçladık. Gereç ve Yöntem: 2014-2017 arasında; kurumumuzda neoadjuvan kemoterapi sonrası opere olan 30 hasta çalışmaya alındı. Hastalara, 3 siklus indüksiyon kemoterapi verildi. İndüksiyon tedavisinin tamamlanmasının ardından tüm hastalara pnömonektomi, lobektomi veya bilobektomi ve lenf nodülü diseksiyonu uygulandı. Genel sağkalım (OS) ve progresyonsuz sağkalımı (PFS) hesaplamak için Kaplan-Meier yöntemi kullanıldı. Tek değişkenli ve çok değişkenli analizlerin, progresyonsuz ve genel sağkalım üzerindeki etkisini değerlendirmek için Cox regresyon analizi yapıldı. Tüm analizler SPSS 23 (IBM SPSS, Armonk, NY, ABD) ile gerçekleştirilmiştir. Bulgular: Neoadjuvan kemoterapi protokolleri histolojik alt tiplere göre seçilmiştir. En çok tercih edilen rejim, skuamöz kanser alt tipi için cisplatin ve gemsitabin kombinasyonu (% 47.1) ve adenokanser için cisplatin ve dosetaksel (% 66.7) idi. Tüm çalışma popülasyonu için progresyonsuz sağkalım 31 ay ve median genel sağkalım 42 aydı. PFS (p: 0.363) ve OS (p: 0.604) kemoterapi rejimleri ile korelasyon göstermedi. Sonuç: Bulgularımız, KHDAK hastalarında kemoterapi rejimlerinin prognostik değere sahip olmadığını göstermektedir, ancak bu bulguları doğrulamak için büyük ölçekli çalışmalara ihtiyaç vardır.

CLINICAL OUTCOMES OF PATIENTS WITH STAGE III LUNG CANCER OPERATED AFTER NEOADJUVANT CHEMOTHERAPY: EFFECT OF CHEMOTHERAPY REGIMEN

Introduction: The neoadjuvant therapeutic approach remains one of the most debated topics in NSCLCtreatment. In this study, we aimed to evaluate patients with stage III NSCLC retrospectively, who were operatedafter neoadjuvant chemotherapy in a single instution and compare the long term clinical outcomes according tothe chemotherapy protocols.Material and Method: Between 2014 and 2017; 30 patients who had surgery for NSCLC after neoadjuvantchemotherapy at our institution were included. Patients received 3 cycles of one of the induction chemotherapyschedules. Following completion of induction therapy, all patients underwent resection of the primary tumor, interms of pneumonectomy, lobectomy, or bilobectomy and lymph node dissection. Kaplan-Meier curves were usedto calculate the overall survival (OS) and progression free survival (PFS). Univariate analyses and multivariateanalyses were performed by the Cox proportional hazards model to assess the influence of variables onprogression free and overall survival. All analyses were performed with SPSS version 23 (IBM SPSS, Armonk,NY, USA).Results: Neoadjuvant chemotherapy protocols were chosen according to histological subtype. The mostpreferred regimen was cisplatin plus docetaxel (66.7%) for adenocancer subtype and cisplatin and gemcitabinecombination(47.1%) for squamous cancer subtype. Progression free survival was 31 months and the medianoverall survival for the whole study population was 42 months. Neither PFS (p: 0.363) nor OS (p:0.604) did notcorrelate with chemotherapy regimens.Conclusion: Our results suggest that chemotherapy regimens do not have prognostic value in NSCLC patientswho but large scale trials are needed to confirm this findings.

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Andre F, Grunenwald D, Pignon JP, Dujon A, Pujol JL, Brichon PY, et al. Survival of patients with resected N2 non-small- cell lung cancer: evidence for a subclassification and implications. J Clin Oncol 2000; 18(16): 2981–9.
Lewis J, Gillaspie EA, Osmundson EC, Horn L. Before or After: Evolving neoadjuvant approaches to locally advanced non- small cell lung cancer. Frontiers in Oncology 2018; 8: 5.
Biesma B, Manegold C, Smit HJ, Willems L, Legrand C, Passioukov A, et al. Docetaxel and cisplatin as induction chemotherapy in patients with pathologically-proven stage IIIA N2 non-small cell lung cancer: a phase II organization for research and treatment of cancer (EORTC 08984). Eur J Cancer 2006; 42(10): 1399–406.
Garrido P, Gonzalez-Larriba JL, Insa A, Provencio M, Torres A, Isla D, et al. Long-term survival associated with complete resection after induction chemotherapy in stage IIIA (N2) and IIIB (T4N0-1) non small-cell lung cancer patients: the Spanish Lung Cancer Group Trial 9901. J Clin Oncol 2007; 25(30): 4736–42.
Chaft JE, Rusch V, Ginsberg MS, Paik PK, Finley DJ, Kris MG, et al. Phase II trial of neoadjuvant bevacizumab plus chemotherapy and adjuvant bevacizumab in patients with resectable nonsquamous non-small-cell lung cancers. J Thorac Oncol 2013; 8(8): 1084–90.
Ou W, Li N, Wang SY, Li J, Liu QW, Huang QA, et al. Phase 2 trial of neoadjuvant bevacizumab plus pemetrexed and carboplatin in patients with unresectable stage III lung adenocarcinoma (GASTO 1001). Cancer 2016; 122(5): 740–7.
Burdett S, Stewart LA, Rydzewska L. A systematic review and meta-analysis of the literature: chemotherapy and surgery versus surgery alone in non- small cell lung cancer. J Thorac Oncol 2006; 1(7): 611–21.
NSCLC Meta-analysis Collaborative Group: Preoperative chemotherapy for non-small cell lung cancer: A systematic review and meta-analysis of individual participant data. Lancet 2014; 383(9928): 1561-71.
Vokes EE, Herndon JE II, Crawford J, Leopold KA, Perry MC, Miller AA, et al. Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small cell lung cancer: Cancer and leukemia group B study 9431. J Clin Oncol 2002; 20(20): 4191-98.
O'Brien ME, Splinter T, Smit EF, Biesma B, Krzakowski M, Tjan-Heijnen VC, et al. Carboplatin and paclitaxel (Taxol) as an induction regimen for patients with biopsy proven stage IIIA N2 non-small cell lung cancer. An EORTC phase II study (EORTC 08958). Eur J Cancer 2003; 39(10): 1416-22.
Zarogoulidis K, Kontakiotis T, Hatziapostolou P, Fachantidou E, Delis D, Goutsikas J, et al. A Phase II study of docetaxel and carboplatin in the treatment of non-small cell lung cancer. Lung Cancer 2001; 32(3): 281-7.
De Marinis F, Nelli F, Migliorino MR, Martelli O, Cortesi E, Treggiari S, et al. Gemcitabine, paclitaxel, and cisplatin as induction chemotherapy for patients with biopsy-proven stage IIIA(N2) nonsmall cell lung carcinoma: a phase II multicenter study. Cancer 2003; 98(8): 1707–15.
Cappuzzo F, Selvaggi G, Gregorc V, Mazzoni F, Betti M, Rita Migliorino M, et al. Gemcitabine and cisplatin as induction chemotherapy for patients with unresectable stage IIIA-bulky N2 and stage IIIB non small cell lung carcinoma: an Italian Lung Cancer Project Observational Study. Cancer 2003; 98(1): 128–34.
Burkes RL, Shepherd FA, Blackstein ME, Goldberg ME, Waters PF, Patterson GA, et al. Induction chemotherapy with mitomycin, vindesine, and cisplatin for stage IIIA (T1-3, N2) unresectable non-small-cell lung cancer: final resultsof the Toronto phase II trial. Lung Cancer 2005; 47(1): 103–9.
Martin J, Ginsberg RJ, Venkatraman ES, Bains MS, Downey RJ, Korst RJ, et al. Long-term results of combined modality therapy in resectable non-small cell lung cancer. J Clin Oncol 2002; 20(8): 1989-95.
Garrido P, González-Larriba JL, Insa A, Provencio M, Torres A, Isla D, et al. Long-term survival associated with complete resection after induction chemotherapy in stage IIIA (N2) and IIIB (T4N0-1) non small cell lung cancer patients: The Spanish Lung Cancer Group Trial 9901. J Clin Oncol 2007; 25(30): 4736-42.
Krzakowski M, Provencio M, Utracka-Hutka B, Villa E, Codes M, Kuten A, et al. Oral vinorelbine and cisplatin as induction chemotherapy and concomitant chemo-radiotherapy in stage III non-small cell lung cancer: Final results of an international phase II trial. J Thorac Oncol 2008; 3(9): 994-1002.
Martini N, Kris MG, Flehinger BJ, Gralla RJ, Bains MS, Burt ME, et al. Preoperative chemotherapy for stage IIIa (N2) lung cancer: The Sloan-Kettering experience with 136 patients. Ann Thorac Surg 1993; 55(6): 1365-73.
Kumar P, Herndon J, Elias AD, Sugarbaker DJ, Green MR. Comparison of pre-operative thoracic radiation therapy (TRT) to pre-operative chemotherapy (CT) in surgically staged IIIA(N2) non-small cell lung cancer (NSCLC): Initial results of cancer and leukemia group B (CALGB) phase III protocol 9134. Int J Radiation Oncol Biol Phys 1997; 39(2): 195.
Eberhardt W, Wilke H, Stamatis G, Stuschke M, Harstrick A, Menker H, et al. Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a phase II trial. J Clin Oncol 1998; 16(2): 622–34.
Gilligan D, Nicolson M, Smith I, Groen H, Dalesio O, Goldstraw P, et al. Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review. Lancet 2007; 369(9577): 1929–37.
Evans NR III, Li S, Wright CD, Allen MS, Gaissert HA.The impact of induction therapy on morbidity and operative mortality after resection of primary lung cancer. J Thorac Cardiovasc Surg 2010; 139(4): 991–6.