Küçük hücreli akciğer kanseri tanısı alan hastalarımızın prospektif incelemesi: Tek merkezli çalışma

Year 2020, , 1008 - 1012, 01.11.2020

Tibel Tuna , Levent Erkan , Oguz Uzun

https://doi.org/10.28982/josam.812077

Abstract

Amaç: Küçük hücreli akciğer kanseri en saldırgan akciğer kanseri türüdür. Küçük hücreli dışı akciğer kanserinin aksine son 30 yılda tedavide kaydadeğer bir ilerleme gösterilememiştir. Biz bu çalışmada SCLC hastalarının demografik, klinik, radyolojik özelliklerini, sigara ile ilişkisini, tedavi gecikmelerini, tedavi yanıtları, toksisiteleri, prognoza etki eden faktörleri ve yaşam sürelerini incelemeyi amaçladık.
Yöntemler: Samsun Ondokuz Mayıs Üniversitesi Tıp Fakültesi Göğüs Hastaıklarında 4 yıllık sürede küçük hücreli akciğer kanseri tanısı alan hastalar prospektif kohort çalışmamıza dahil edildi. Hastaların demografik özellikleri, semptomları, performans durumları, laboratuvar, radyolojik, bronkskopik bulguları, evreleme tetkikleri, semptom başlangıcından bölümümüze müracat, müracattan tanıya kadar geçen süreler, kemoterapi yanıt ve toksisiteleri kaydedildi. Takipler bölümümüzde yapıldı. Hastanemiz dışında vefat eden hastaların ölüm tarihleri nüfus müdürlüğünden alındı. Takipten çıkan, eksik verisi olan veya onam vermeyen hastalar çalışmadan çıkarıldı.
Bulgular: Çalışma grubu 88 hastadan oluşuyordu. Bu hastaların 82’si erkek, 6’sı kadındı. Ortalama yaş 61,16 idi. Başvuru anındaki esas semptomlar öksürük (%77), yorgunluk (%62), dispne (%60) olarak tespit edildi. Tanı anında hastaların %39’u sınırlı hastalık iken %61’i yaygın evrede idi. İlk semptomdan kliniğimize başvurana kadar geçen sure ortalama 30 gün, tanı konulmasına kadar geçen süre ise 10 gündü. 77 hastaya birinci basamak tedavi olarak cisplatin/carboplatin-etoposide, ikinci basamak tedavi olarak da irinotecan uygulandı. Genel ortalama yaşam süresi 355 (30,8) gün olup sınırlı hastalıkta 416 (47) gün, yaygın hastalıkta 29 (48) gün olarak bulundu (P=0,003). 6 aylık kümülatif survival %76 iken, 12 aylık kümulatif survival %44 idi. Tek değişkenli analalizlerde LDH seviyeleri artışı, performans skoru (PS) >1, yaygın hastalık ve kilo kaybı kötü prognostik faktörlerdi (P=0,042, 0,001, 0,003, 0,022). Çok değişkenli analizlerde ise serum LDH seviyeleri, performans skoru >1 ve yaygın hastalık bağımsız kötü prognostik faktörler olarak belirlendi.
Sonuç: Kadın hasta oranımız halen dünya ortalaması altında. Hastaların kabulünden tanı konulana kadar geçen süre çoğu gelişmiş ülkeden daha kısa olmasına rağmen tedaviye yanıt oranları ve yaşam süreleri dünyada bildirilenlerin alt sınırındaydı. Evre, PS, LDH bağımsız prognostik faktor olarak kullanılabilir.

Keywords

Küçük hücreli akciğer kanseri, Kemoterapi, Prognoz, Yaşam süresi

Prospective evaluation of patients with small cell lung cancer: A single center study

Abstract

Aim: Small cell lung cancer (SCLC) is the most aggressive form of lung cancer. No major treatment advances have occurred for SCLC over the past 30 years, unlike non-small cell lung cancer (NSCLC). We aimed to prospectively examine demographic, clinical, radiological properties, its association with cigarette smoking, delays in diagnosis, treatment responses, toxicities, prognostic factors, and survivals.
Methods: Patients diagnosed with small cell lung cancer during 4 years in Ondokuz Mayıs University, Department of Chest Diseases were included in our prospective cohort study. The demographic characteristics of the patients, symptoms, performance status, laboratory, radiologic, bronchoscopy findings, staging procedures, periods from the initiation of the symptoms to the admission of the patients to our department and definitive diagnosis, chemotherapy responses and toxicities were recorded. Follow-ups were performed in our clinic. Dates of deaths of patients who died outside our hospital were followed up from the records of census directorate. Patients that we lost to follow up, with missing data, or those who did not give consent for participation in the study were excluded.
Results: The study group consisted of 88 patients (82 males, 6 females). The mean age was 61.16 years. The main symptoms on admission were cough (77%), fatigue (62%), dyspnea (60%). Among all, 39% of patients had limited disease whereas the remaining 61% were extensive. The median delay between the occurrence of first symptom and the patient’s presentation to our clinic was 30 days and the median delay before diagnosis was 10 days. Seventy-seven patients were given cisplatin/carboplatin-etoposide as the first line and irinotecan as second line chemotherapy. Overall median survival was 355 (30.8) days, 416 (47) days in limited stage and 296 (48) days in the extensive stage (P=0.003). Six-month cumulative survival was 76%, and 12-month cumulative survival was 44%. Univariate analysis showed that increased LDH levels, performance score >1, extensive stage and weight loss were poor prognostic factors (P=0.042, 0.001, 0.003, 0.022). In multivariate analysis, serum LDH levels, performance score >1 and extensive disease were independent poor prognostic factors.
Conclusion: The ratio of our female patients is still much lower than the world average. Time from the admission of our patients to diagnosis was shorter than most of the developed countries. However, treatment response rates and survival periods were within lower limits of world reports. Stage, PS, LDH can be used as independent prognostic factors.

Keywords

Small cell lung cancer, chemotherapy, Prognosis, survival

References

• 1. Ettinger DS, Aisner J. Changing face of small-cell lung cancer: real and artifact. J Clin Oncol. 2006; 24:4526–7. doi: 10.1200/JCO.2006.07.3841.
• 2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10-29. doi: 10.3322/caac.20138.
• 3. Byers LA, Rudin CM. Small cell lung cancer: where do we go from here? Cancer.2015;121:664-72. doi: 10.1002/cncr.29098.
• 4. Oronsky B, Reid TR, Oronsky A, Carter CA. What's New in SCLC? A Review. Neoplasia. 2017;19(10):842–7. doi: 10.1016/j.neo.2017.07.007.
• 5. WHO, Handbook for reporting results of cancer treatment, in WHO Offset publication No.48. 1979; 745.Geneva.
• 6. Zelen M. Keynote address on biostatistics and data retrieval. Cancer Chemother Rep 3. 1973;4 (2):31-42.
• 7. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Dancey J, Arbuck S, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). European Journal Of Cancer. 2009;45:228–47. doi: 10.1016/j.ejca.2008.10.026.
• 8. Bozkurt B, Selçuk T, Fırat P, Kalyoncu AF, Artvinli M. 1972–2002 döneminde Hacettepe Üniversitesi Tıp Fakültesi Hastanesi’nde akciğer kanseri tanısı konulan hastaların histolojik ve epidemiyolojik değerlendirmesi. Toraks Dergisi. 2004;5(3):143-8.
• 9. Ferlay J, Autier P, Boniol M, , Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Annals of Oncology. 2007;18(3):581-92. doi: 10.1093/annonc/mdl498.
• 10. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71. doi: 10.3322/CA.2007.0010.
• 11. Bernhardt EB, Jalal SI. Small cell lung cancer Cancer Treat Res. 2016;170:301-22. doi: 10.1007/978-3-319-40389-2_14.
• 12. OU SH, Ziogas A, Zell JA. Prognostic factors for survival in extensive stage small cell lung cancer (ED-SCLC): the importance of smoking history, socioeconomic and marital statuses, and ethnicity. J Thorac Oncol. 2009 Jan;4(1):37-43. doi: 10.1097/JTO.0b013e31819140fb.
• 13. Yang P, Allen M, Aubry M, Wampfler J, Marks RS, Edell ES, et al. Clinical Features of 5,628 Primary Lung Cancer Patients. Chest. 2005;128:452-62. doi: 10.1378/chest.128.1.452
• 14. Wang S, Zimmermann S, Parikh K, Mansfield AS, Adjei AA. Current Diagnosis and Management of Small-Cell Lung Cancer Mayo Clin Proc. 2019 Aug;94(8):1599-1622. doi: 10.1016/j.mayocp.2019.01.034.
• 15. Salomaa ER, Sällinen S, Hiekkanen H, Lippo K. Delays in the diagnosis of lung cancer. CHEST 2005;128: 2282-88. doi: 10.1378/chest.128.4.2282.
• 16. Koyi H, Hillerdal G, Branden E. Patient’s and doctor’s delays in the diagnosis of chest tumors. Lung Cancer. 2002;35:53-7. doi: 10.1016/s0169-5002(01)00293-8.
• 17. Erbaycu AE, Özsöz A, Çakan A. Akciğer kanserinde tanı gecikmesine hastanın ve hekimin etkisi. Solunum Hastalıkları. 2005;16:161-65.
• 18. Özlü T, Bülbül Y, Öztuna F, Çan G. Akciğer kanseri tanısını ne kadar sürede koyabiliyoruz? Tüberküloz ve toraks dergisi. 2002;50:288-91.
• 19. Yılmaz A, Aybatlı A. Akciğer kanseri tanı ve tedavisinde gecikmeler. Toraks Dergisi. 2005;6(1):68-72.
• 20. Webb RW, Higgins CB, ed. Lung cancer and bronchopulmonary neoplasms. In:Thoracic imaging Pulmonary and cardiovascular radiology. Lippincott Williams and Wilkins: Philadelphia. 2005;3:75-9.
• 21. Rivera MP, Mehta AC; American College of Chest Physicians. Initial diagnosis of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition) Chest. 2007 Sep;132(3 Suppl):131S-148S. doi: 10.1378/chest.07-1357.
• 22. Cohen MH, Makuch R, Johnston-Early A, Ihde DC, Bunn PA Jr, Fossieck BE Jr et al. Laboratory parameters as an alternative to performance status in prognostic stratification of patients with small cell lung cancer. Cancer Treat Rep. 1981;65:187-95.
• 23. Bremnes M, Sundstrom S, Aasebø U, Kaasa S, Hatlevoll R, Aamdal S. The value of prognostic factors in small cell lung cancer: results from a randomised multicenter study with minimum 5 year follow-up. Lung Cancer. 2003;39:303–13. doi: 10.1016/s0169-5002(02)00508-1.
• 24. Quoix E, A Purohit, M Faller-Beau M, Moreau L, Oster JP, Pauli G. Comparative prognostic value of lactate dehydrogenase and neuron-specific enolase in small-cell lung cancer patients treated with platinum-based chemotherapy. Lung Cancer. 2000;30:127–34. doi: 10.1016/s0169-5002(00)00131-8.
• 25. Paesmans M, Sculier JP, Lecomte J, Thiriaux J, Libert P, Sergysels R,et al. Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years. Cancer 2000;89:523–33. doi: 10.1002/1097-0142(20000801)89:3<523:aid-cncr7>3.0.co;2-6.
• 26. Deng T, Zhang J, Meng Y, Zhou Y, Li W. Higher pretreatment lactate dehydrogenase concentration predicts worse overall survival in patients with lung cancer. Medicine Baltimore). 2018 Sep;97(38):e12524. doi: 10.1097/MD.0000000000012524.
• 27. Osterlind K, Hansen HH, Hansen M, Dombernowsky P, Andersen PK. Long-term disease-free survival in small-cell carcinoma of the lung: a study of clinical determinants. J Clin Oncol. 1986;4:1307–13. doi: 10.1200/JCO.1986.4.9.1307.
• 28. Li J, Dai CH, Chen P, Wu JN, Bao QL, Qiu H, et al. Survival and prognostic factors in small cell lung cancer. J Med Oncol. 2010 Mar,27(1):73-81. doi: 10.1007/s12032-009-9174-3.
• 29. Rawson N, Peto J, An overview of prognostic factors in small cell lung cancer. A report from the Subcommittee for the Management of Lung Cancer of the United Kingdom Coordinating Committee on Cancer Research. Br J Cancer. 1990;61(4):597-604. doi: 10.1038/bjc.1990.133.
• 30. Tamura M, Ueoka H, Kiura K, Tabata M, Shibayama T, Miyatake K et al. Prognostic factors of small-cell lung cancer in Okayama Lung Cancer Study Group Trials. Acta Med Okayama. 1998;52(2):105–11. doi: 10.18926/AMO/31310.
• 31. Arınç S, Gönlügür U, Devran O, Erdal N, Ece F, Ertugrul M et al. Prognostic factors in patients with small cell lung carcinoma. Med Oncol. Apr 2010. doi: 10.1007/s12032-009-9198-8.
• 32. Mao Y, Hu J, Ugnat AM, Semenciw R, Fincham S. Socioeconomic status and lung cancer risk in Canada. Int J Epidemiol. 2001;30:809–817. doi: 10.1093/ije/30.4.809.
• 33. Jackman DM, Johnson BE. Small cell lung cancer. Lancet. 2005;366:1385-96. doi: 10.1016/S0140-6736(05)67569-1.
• 34. Buccheri G, Ferrigno D. Prognostic factors in lung cancer: tables and comments. Eur Respir J. 1994;7(7):1350–64. doi: 10.1183/09031936.94.07071350.