Küçük Hücreli Akciğer Kanseri
Özet
Küçük Hücreli Akciğer Kanseri (KHAK), dünya genelinde azalan bir insidansa rağmen ciddi bir sağlık sorunu olmaya devam etmektedir. Genellikle sigara içicilerde görülür ve hızlı büyüme oranı, erken metastaz eğilimi ile bilinir. Klinik olarak öksürük, nefes darlığı ve kilo kaybı gibi belirtilerle başlar, tanısı ışık mikroskobuyla koyulurken nöroendokrin belirteçler tanıda destekleyicidir.
Tedavide sınırlı evrede cerrahi, kemoterapi ve radyoterapi kombinasyonları uygulanırken, yaygın evrede platin bazlı kemoterapi ve immünoterapiler ön plandadır. Torasik radyoterapi ve profilaktik kraniyal ışınlama, belirli hastalarda tedavinin etkinliğini artırır. Prognostik faktörler arasında hastalık evresi, performans durumu ve kilo kaybı önemlidir. Tedaviye rağmen çoğu hasta nüks yaşar ve medyan sağkalım süresi sınırlıdır.
KHAK hastalarının takibi, tedavi sonrası nüks ve metastazları erken saptamak için kritik önemdedir. Tedavi sonrası izlem, erken nüksleri ve metastazları saptamak için düzenli görüntüleme yöntemleriyle yapılmalıdır. Sınırlı evrede takip, ilk 1–2 yılda her 3 ayda bir, sonraki yıllarda ise 6 aylık periyotlarla anamnez, fizik muayene ve toraks-batın BT gibi görüntüleme yöntemlerini içerir. Beyin metastazlarının yaygınlığı nedeniyle ilk yıllarda sık beyin MR’ı önerilir. Yaygın evrede ise 2-3 ayda bir sık takip gereklidir. Takip sırasında yeni akciğer nodülleri veya beyin metastazları gelişimi yakından izlenir. Profilaktik kraniyal ışınlama (PKI) uygulanmayan hastalarda beyin MR takibi daha da önem taşır. Takip, tedavi yanıtlarını değerlendirmenin yanı sıra hastaların yaşam kalitesini artırmayı ve ilerleyen hastalıkların erken yönetimini sağlamayı amaçlar. Modern izlem stratejileri ile sağkalım oranlarında artış hedeflenmektedir.
Small Cell Lung Cancer (SCLC) remains a significant global health issue despite a decreasing incidence worldwide. It is predominantly observed in smokers and is characterized by a high growth rate and early tendency for metastasis. Clinically, it often presents with symptoms such as cough, shortness of breath, and weight loss. Diagnosis is primarily established through light microscopy, with neuroendocrine markers serving as supportive diagnostic tools.
For limited-stage SCLC, treatment typically involves a combination of surgery, chemotherapy, and radiotherapy. In extensive-stage disease, platinum-based chemotherapy and immunotherapies are the primary options. Thoracic radiotherapy and prophylactic cranial irradiation (PCI) are employed in select patients to enhance treatment efficacy. Prognostic factors include disease stage, performance status, and weight loss. Despite treatment, most patients experience relapse, and the median survival remains limited.
Follow-up for SCLC patients is critical for the early detection of recurrence and metastases after treatment. Post-treatment surveillance includes regular imaging studies. For limited-stage disease, follow-up involves history-taking, physical examination, and imaging studies such as chest and abdominal CT scans every three months during the first 1–2 years and every six months thereafter. Due to the high prevalence of brain metastases, frequent brain MRI is recommended in the early years. In extensive-stage disease, closer follow-up every 2–3 months is required. During follow-up, the development of new lung nodules or brain metastases is carefully monitored. Brain MRI is particularly important in patients who did not receive PCI.
The purpose of follow-up is not only to evaluate treatment responses but also to enhance patients’ quality of life and ensure early management of disease progression. Modern follow-up strategies aim to improve survival outcomes through early detection and timely intervention.
Referanslar
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence ve mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71(3):209–249.
Subramanian J, Govindan R. Lung cancer in never smokers: a review. J Clin Oncol 2007; 25:561.
Wang Q, Gümüş ZH, Colarossi C, et al. SCLC: Epidemiology, Risk Factors, Genetic Susceptibility, Molecular Pathology, Screening, and Early Detection. J Thorac Oncol 2023; 18:31
Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol 2015; 10:1243.
Travis WD. Lung cancer pathology: current concepts. Clin Chest Med 2020;41:67-85. doi:10.1016/j.ccm.2019.11.001. PMID: 32008630.
Moran CA, Suster S, Coppola D, et al. Neuroendocrine carcinomas of the lung: a critical analysis. Am J Clin Pathol 2009;131:206-221. doi:10.1309/AJCP9H1OTMUCSKQW. PMID: 19141381.
Thunnissen E, Borczuk AC, Flieder DB, et al. The use of immunohistochemistry improves the diagnosis of small cell lung cancer ve its differential diagnosis. An international reproducibility study in a demanding set of cases. J Thorac Oncol 2017;12(2):334–346.
Baine MK, Hsieh M-S, Lai WV, et al. SCLC subtypes defined by ASCL1, NEU¬ROD1, POU2F3, ve YAP1: A comprehensive immunohistochemical ve histo¬pathologic characterization. J Thorac Oncol 2020;15(12):1823–1835.
George J, Lim JS, Jang SJ, et al. Comprehensive genomic profiles of small cell lung cancer. Nature 2015; 524:47.
Kaye FJ. RB and cyclin dependent kinase pathways: defining a distinction between RB and p16 loss in lung cancer. Oncogene 2002; 21:6908.
Sculier JP, Evans WK, Feld R, et al. Superior vena caval obstruction syndrome in small cell lung cancer. Cancer 1986;57:847–851.
Verbalis JG, Grossman A, Hoybye C, et al. Review ve analysis of differing regu¬latory indications ve expert panel guidelines for the treatment of hyponatremia. Curr Med Res Opin 2014;30:1201–1207.
Zelen M. Keynote address on biostatistics ve data retrieval. Cancer Chemo¬ther Rep 1973;4(2):31–42.
Paesmans M, Sculier JP, Lecomte J, 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.
Martínez-García E, Irigoyen M, González-Moreno O, et al. Repetitive nicotine exposure leads to a more malignant and metastasis-prone phenotype of SCLC: a molecular insight into the importance of quitting smoking during treatment. Toxicol Sci 2010; 116:467.
Gronowitz JS, Bergström R, Nôu E, et al. Clinical ve serologic markers of stage ve prognosis in small cell lung cancer. A multivariate analysis. Cancer 1990;66(4):722–732.
Paesmans M, Sculier JP, Lecomte J, 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(3):523–533.
Shepherd FA, Laskey J, Evans WK, et al. Cushing’s syndrome associated with ectopic corticotropin production ve small-cell lung cancer. J Clin Oncol 1992;10(1):21–27.
Lassen U, Osterlind K, Hansen M, et al. Long-term survival in small-cell lung cancer: Posttreatment characteristics in patients surviving 5 to 18+ years–an analysis of 1,714 consecutive patients. J Clin Oncol 1995;13(5):1215–1220.
Hiltermann TJN, Pore MM, van den Berg A, et al. Circulating tumor cells in small-cell lung cancer: A predictive ve prognostic factor. Ann Oncol 2012;23(11):2937–2942.
Vallières E, Shepherd FA, Crowley J, et al. The IASLC Lung Cancer Staging Project: proposals regarding the relevance of TNM in the pathologic staging of small cell lung cancer in the forthcoming (seventh) edition of the TNM classification for lung cancer. J Thorac Oncol 2009; 4:1049.
Wakeam E, Acuna SA, Leighl NB, et al. Surgery Versus Chemotherapy and Radiotherapy For Early and Locally Advanced Small Cell Lung Cancer: A Propensity-Matched Analysis of Survival. Lung Cancer 2017; 109:78.
Rossi A, Di Maio M, Chiodini P, et al. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin Oncol 2012; 30:1692.
Kubota K, Hida T, Ishikura S, et al. Etoposide and cisplatin versus irinotecan and cisplatin in patients with limited-stage small-cell lung cancer treated with etoposide and cisplatin plus concurrent accelerated hyperfractionated thoracic radiotherapy (JCOG0202): a randomised phase 3 study. Lancet Oncol 2014; 15:106.
Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet 2019; 394:1929.
Warde P, Payne D. Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis. J Clin Oncol 1992; 10:890.
Kies MS, Mira JG, Crowley JJ, et al. Multimodal therapy for limited small-cell lung cancer: a randomized study of induction combination chemotherapy with or without thoracic radiation in complete responders; and with wide-field versus reduced-field radiation in partial responders: a Southwest Oncology Group Study. J Clin Oncol 1987; 5:592.
Simone CB 2nd, Bogart JA, Cabrera AR, et al. Radiation Therapy for Small Cell Lung Cancer: An ASTRO Clinical Practice Guideline. Pract Radiat Oncol 2020; 10:158.
Perry MC, Eaton WL, Propert KJ, et al. Chemotherapy with or without radiation therapy in limited small-cell carcinoma of the lung. N Engl J Med 1987; 316:912.
Rosenthal S, Tattersall MH, Fox RM, et al. Adjuvant thoracic radiotherapy in small cell lung cancer: Ten year follow-up of a randomized study. Lung Cancer 1991; 7:235.
Takada M, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol 2002; 20:3054.
IMFINZI (durvalumab) injection, for intravenous use. United States prescribing information. Revised December 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761069s049lbl.pdf (Accessed on December 06, 2024).
NCCN guidelines. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site (Accessed on April 04, 2013).
Hochstenbag MM, Twijnstra A, Wilmink JT, et al. Asymptomatic brain metastases (BM) in small cell lung cancer (SCLC): MR-imaging is useful at initial diagnosis. J Neurooncol 2000; 48:243.
Arriagada R, Le Chevalier T, Borie F, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. J Natl Cancer Inst 1995; 87:183.
Aupérin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999; 341:476.
Meert AP, Paesmans M, Berghmans T, et al. Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis. BMC Cancer 2001; 1:5.
Xu J, Yang H, Fu X, et al. Prophylactic Cranial Irradiation for Patients with Surgically Resected Small Cell Lung Cancer. J Thorac Oncol 2017; 12:347.
Zhu H, Guo H, Shi F, et al. Prophylactic cranial irradiation improved the overall survival of patients with surgically resected small cell lung cancer, but not for stage I disease. Lung Cancer 2014; 86:334.
Yang Y, Zhang D, Zhou X, et al. Prophylactic cranial irradiation in resected small cell lung cancer: A systematic review with meta-analysis. J Cancer 2018; 9:433.
Wolfson AH, Bae K, Komaki R, et al. Primary analysis of a phase II randomized trial Radiation Therapy Oncology Group (RTOG) 0212: impact of different total doses and schedules of prophylactic cranial irradiation on chronic neurotoxicity and quality of life for patients with limited-disease small-cell lung cancer. Int J Radiat Oncol Biol Phys 2011; 81:77.
Daly ME, Ismaila N, Decker RH, et al. Radiation Therapy for Small-Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline. J Clin Oncol 2021; 39:931.
Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007; 357:664.
Slotman BJ, Mauer ME, Bottomley A, et al. Prophylactic cranial irradiation in extensive disease small-cell lung cancer: short-term health-related quality of life and patient reported symptoms: results of an international Phase III randomized controlled trial by the EORTC Radiation Oncology and Lung Cancer Groups. J Clin Oncol 2009; 27:78.
Johnson BE, Patronas N, Hayes W, et al. Neurologic, computed cranial tomographic, and magnetic resonance imaging abnormalities in patients with small-cell lung cancer: further follow-up of 6- to 13-year survivors. J Clin Oncol 1990; 8:48.
Herskovic AM, Orton CG. Elective brain irradiation for small cell anaplastic lung cancer. Int J Radiat Oncol Biol Phys 1986; 12:427.
Sheline GE, Wara WM, Smith V. Therapeutic irradiation and brain injury. Int J Radiat Oncol Biol Phys 1980; 6:1215.
Ahles TA, Silberfarb PM, Herndon J 2nd, et al. Psychologic and neuropsychologic functioning of patients with limited small-cell lung cancer treated with chemotherapy and radiation therapy with or without warfarin: a study by the Cancer and Leukemia Group B. J Clin Oncol 1998; 16:1954.
Agra Y, Pelayo M, Sacristan M, et al. Chemotherapy versus best supportive care for extensive small cell lung cancer. Cochrane Database Syst Rev 2003; :CD001990.
Giordano KF, Jatoi A, Adjei AA, et al. Ramifications of severe organ dysfunction in newly diagnosed patients with small cell lung cancer: contemporary experience from a single institution. Lung Cancer 2005; 49:209.
Lowenbraun S, Bartolucci A, Smalley RV, et al. The superiority of combination chemotherapy over single agent chemotherapy in small cell lung carcinoma. Cancer 1979; 44:406
Horn L, Mansfield AS, Szczęsna A, et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med 2018; 379:2220.
Durvalumab injection, for intravenous use. United States Prescribing Information. US National Library of Medicine. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761069s018lbl.pdf (Accessed on March 31, 2020).
Takahashi T, Yamanaka T, Seto T, et al. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 2017.
Albain KS, Crowley JJ, Livingston RB. Long-term survival and toxicity in small cell lung cancer. Expanded Southwest Oncology Group experience. Chest 1991; 99:1425.
National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Small cell lung cancer. v1.2016. https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf (Accessed on June 21, 2016).
O'Brien ME, Ciuleanu TE, Tsekov H, et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol 2006; 24:5441.
von Pawel J, Schiller JH, Shepherd FA, et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 1999; 17:658.
Masuda N, Fukuoka M, Kusunoki Y, et al. CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol 1992; 10:1225.
LeChevalier T, Ibrahim N, Chomy P, et al. A phase II study of irinotecan in patients with small cell lung cancer progressing after initial response to first line chemotherapy (abstract). Proc Am Soc Clin Oncol 1997; 16:450a.
DeVore R, Blanke C, Denham C, et al. Phase II study of irinotecan in patients with previously treated small cell lung cancer (abstract). Proc Am Soc Clin Oncol 1998; 17:451a.
Naito Y, Yamada K, Imamura Y, et al. Rechallenge treatment with a platinum-based regimen in patients with sensitive relapsed small-cell lung cancer. Med Oncol 2018; 35:61.
Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med 2023; 389:2063.
Dowlati A, Hummel HD, Champiat S, et al. Sustained Clinical Benefit and Intracranial Activity of Tarlatamab in Previously Treated Small Cell Lung Cancer: DeLLphi-300 Trial Update. J Clin Oncol 2024; 42:3392.
Virgo KS, McKirgan LW, Caputo MC, et al. Post-treatment management options for patients with lung cancer. Ann Surg 1995;222:700–710.
Altorki N, Kent M, Pasmantier M. Detection of early-stage lung cancer: computed tomographic scan or chest radiograph? J Thorac Cardiovasc Surg. 2001;121:1053–7.
Manapov F, Klocking S, Niyazi M, et al. Timing of failure in limited disease (stage I-III) small-cell lung cancer patients treated with chemoradiotherapy: a retrospective analysis. Tumori 2013;99:656-660.
