Small Cell Lung Cancer

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Practice Essentials

Small cell lung cancer (SCLC), previously known as oat cell carcinoma, is considered distinct from other lung cancers, which are called non–small cell lung cancers (NSCLCs) because of their clinical and biologic characteristics. See the image below.



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High-power photomicrograph of small cell carcinoma on the left side of the image with normal ciliated respiratory epithelium on the right side of the ....

See Small Cell Lung Cancer: Beating the Spread, a Critical Images slideshow, to help identify the key clinical and biologic characteristics of small cell lung cancer, the staging criteria, and the common sites of spread.

Also, see the Clinical Presentations of Lung Cancer: Slideshow and Lung Cancer Staging -- Radiologic Options slideshows for additional information on SCLC staging and treatment.

SCLC is an aggressive subtype of lung cancer. Without treatment, in a few weeks it could be fatal. It is important to determine if the cancer is limited or at an extensive stage. Limited-stage cancer is treated with chemotherapy and radiation. Extensive-stage cancer is treated with chemotherapy alone.

SCLC is a neuroendocrine carcinoma that exhibits aggressive behavior, rapid growth, early spread to distant sites, exquisite sensitivity to chemotherapy and radiation, and frequent association with distinct paraneoplastic syndromes, including hypercalcemia, Eaton-lambert syndrome, syndrome of inappropriate diuretic hormone, and many others. (See Pathophysiology, Etiology, and Presentation.)[1, 2, 3]

Pathophysiology

Small cell lung carcinoma (SCLC) arises in peribronchial locations and infiltrates the bronchial submucosa. Widespread metastases occur early in the course of the disease, with common spread to the mediastinal lymph nodes, liver, bones, adrenal glands, and brain.

In addition, production of various peptide hormones leads to a wide range of paraneoplastic syndromes; the most common of these are the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and the syndrome of ectopic adrenocorticotropic hormone (ACTH) production. In addition, autoimmune phenomena may lead to various neurologic syndromes, such as Lambert-Eaton syndrome.

Etiology

The predominant cause of small cell lung cancer (SCLC) (and non-SCLC) is tobacco smoking. Of all histologic types of lung cancer, SCLC and squamous cell carcinoma have the strongest correlation to tobacco.[4, 5] Approximately 98% of patients with SCLC have a smoking history. Patients with SCLC should be encouraged to stop smoking, as smoking cessation is associated with improved survival.[6]

All types of lung cancer occur with increased frequency in uranium miners, but SCLC is the most common. The incidence of lung cancer is increased further in these individuals if they also smoke tobacco.

Exposure to radon, an inert gas that is a product of uranium decay, has also been reported to cause SCLC.

Epidemiology

Occurrence in the United States

Lung cancer overall is the second most common malignancy in both sexes in the United States, exceeded in frequency only by prostate cancer in men and breast cancer in women.[7, 8, 9, 10] Although less than half as many new cases of lung cancer than breast cancer are diagnosed in US women each year, almost twice as many US women die of lung cancer each year than from breast cancer.

The incidence of small cell lung cancer (SCLC) has declined over the last few years. SCLC once accounted for 20-25% of all newly diagnosed lung cancers; it now comprises only about 15% of all lung cancers.[11]

For 2016, the estimates for lung cancer overall are 224,390 new cases and 158,080 deaths in the United States.[10]

International occurrence

Globally, lung cancer is the most frequent malignancy in men (in Europe, lung cancer is second only to prostate cancer[12] ) and the fifth most common cancer in women. Although the incidence of lung cancer has been falling in the US, it is increasing at a staggering pace in developing countries due to the rising prevalence of tobacco use. According to World Health Organization (WHO) statistics, about 1.59 million deaths from lung cancer occur annually throughout the world.[13]

Separate worldwide data for small cell carcinoma are not available. The incidence of lung cancer started to decline among males in the early 1980s and has continued to do so over the past 20 years. In contrast, the incidence in women started to increase in the late 1970s and did not begin to decline until the mid-2000s.[7, 10]

Age-related demographics

As with other histopathologic types of lung cancer, most cases of SCLC occur in individuals aged 60-80 years.

Prognosis

Approximately 60-70% of patients with small cell lung cancer (SCLC) have clinically disseminated or extensive disease at presentation. Extensive-stage SCLC is incurable. When given combination chemotherapy, patients with extensive-stage disease have a complete response rate of more than 20% and a median survival longer than 7 months; however, only 2% are alive at 5 years.[14] For individuals with limited-stage disease that is treated with combination chemotherapy plus chest radiation, a complete response rate of 80% and survival of 17 months have been reported; 12-15% of patients are alive at 5 years.[15]

Genome-wide association studies have identified single-nucleotide polymorphisms (eg, within the promoter region of YAP1 on chromosome 11q22) that may affect survival in patients with SCLC.[16, 17]  

Indicators of poor prognosis include the following:

Patient Education

Because tobacco smoking is the predominant cause of lung cancer, the only means of decreasing the incidence of this disease overall, as well as that of small cell lung cancer (SCLC) specifically, is to decrease the prevalence of smoking. The evidence is clear that the declining incidence of lung cancer in men in the United States has coincided with a decrease in smoking among males.

Dexamethasone (Decadron, Dexamethasone Intensol, Dexasone)

Clinical Context:  Dexamethasone is a synthetic adrenocortical steroid with multiple indications. This agent is widely used in combination with serotonin (5-HT) receptor antagonists to prevent nausea and vomiting caused by highly emetogenic agents (eg, cisplatin).

Metoclopramide (Metozolv ODT, Reglan)

Clinical Context:  Metoclopramide is a dopamine antagonist that enhances the response to acetylcholine of tissue in the upper GI tract, causing antiemetic activity. At higher doses, metoclopramide blocks serotonin receptors in the chemoreceptor trigger zone of the central nervous system (CNS).

Ondansetron (Zofran, Zofran ODT, Zuplenz)

Clinical Context:  Ondansetron is a selective serotonin (5-HT3)-receptor antagonist that is used to prevent chemotherapy-induced nausea and vomiting.

Granisetron (Kytril, Granisol, Sancuso)

Clinical Context:  Granisetron is a selective 5-HT3-receptor antagonist that is used to prevent chemotherapy-induced nausea and vomiting.

Dolasetron (Anzemet)

Clinical Context:  Dolasetron binds to 5-HT3 receptors located on vagal neurons in the GI tract, blocking signals to the vomiting center, thus preventing nausea and vomiting.

Palonosetron (Aloxi)

Clinical Context:  Palonosetron is a selective 5-HT3 receptor antagonist with long half-life (40 h) that blocks 5-HT3 receptors peripherally and centrally in the chemoreceptor trigger zone. This agent is indicated for the prevention of chemotherapy-induced nausea and vomiting.

Cyclophosphamide (Cytoxan, Neosar)

Clinical Context:  Cyclophosphamide is chemically related to the nitrogen mustards. As an alkylating agent, the mechanism of action of its active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells. Fatal cardiotoxicity has been reported with coadministration of pentostatin.

Carboplatin (Paraplatin)

Clinical Context:  Carboplatin is a platinum alkylating agent that interferes with the function of DNA by producing interstrand DNA cross-links. It can be used for the treatment of small cell lung cancer (SCLC), which is an off-label indication. Carboplatin has black box warnings, including bone marrow suppression, anaphylactic reactions, and vomiting.

Cisplatin

Clinical Context:  Cisplatin is a platinum-containing compound that exerts an antineoplastic effect by covalently binding to DNA, with preferential binding to the N-7 position of guanine and adenosine. It can react with 2 different sites on DNA to produce cross-links. The platinum complex can also bind to nuclear and cytoplasmic protein. Cisplatin has black box warnings, including anaphylacticlike reactions, ototoxicity, and renal toxicity.

Ifosfamide (Ifex)

Clinical Context:  Ifosfamide is a nitrogen mustard alkylating agent that inhibits DNA and protein synthesis. Although not FDA approved, ifosfamide is often used as a treatment for relapsed SCLC.

Irinotecan (Camptosar)

Clinical Context:  Irinotecan binds reversibly to the topoisomerase I-DNA complex and prevents the ligation of the cleaved DNA strand. It has been used off label for the treatment of extensive-stage small cell lung cancer. Black box warnings for irinotecan include bone marrow suppression and diarrhea.

Topotecan (Hycamtin)

Clinical Context:  Topotecan inhibits topoisomerase I and thereby inhibits DNA replication. This agent may interact with other antineoplastic drugs to cause prolonged neutropenia and thrombocytopenia in addition to increasing morbidity/mortality. Topotecan is indicated for the treatment of relapsed or refractory small cell lung cancer (SCLC).

Doxorubicin (Adriamycin, Caelyx, Rubex)

Clinical Context:  Doxorubicin is an anthracycline antineoplastic that causes DNA strand breakage through its effects on topoisomerase II and through direct intercalation into DNA, which causes DNA polymerase inhibition. It has a labeled indication for the treatment of small cell lung cancer (SCLC). Doxorubicin has several black box warnings, including bone marrow suppression, myocardial toxicity, and secondary malignancy.

Vincristine (Oncovin)

Clinical Context:  Vincristine inhibits tubulin polymerization during mitosis. This agent is G2-phase specific. Vincristine may interact with mitomycin-C and cause an acute pulmonary reaction.

Vinorelbine (Navelbine)

Clinical Context:  Vinorelbine is a vinca alkaloid that inhibits tubulin polymerization during G2 phase of cell division, thereby inhibiting mitosis.

Paclitaxel (Taxol, Abraxane)

Clinical Context:  Paclitaxel promotes microtubule assembly, interferes with the G2 mitotic phase, and inhibits cell replication. It has an off-label indication for the treatment of small cell lung cancer (SCLC). Black box warnings for paclitaxel include bone marrow suppression and hypersensitivity reactions.

Docetaxel (Taxotere, Docefrez)

Clinical Context:  Docetaxel inhibits the depolymerization of tubulin, which inhibits DNA, RNA, and protein synthesis. It can be used for the treatment of relapsed SCLC, which is an off-label indication. Docetaxel has several black box warnings, such as bone marrow suppression, fluid retention, and hypersensitivity reactions. This drug is not recommended for use in certain patients with hepatic impairment. Patients undergoing docetaxel treatment should be premedicated with corticosteroids the day before administration, to help reduce fluid retention and hypersensitivity reactions.

Gemcitabine (Gemzar)

Clinical Context:  Gemcitabine is a pyrimidine analog. After intracellular metabolism to its active nucleotide, it inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA. Although use of this drug as a treatment for refractory or relapsed small cell lung cancer (SCLC) has not been approved by the US Food and Drug Administration (FDA), gemcitabine is often used for this purpose.

Etoposide (Toposar, VePesid)

Clinical Context:  Etoposide inhibits topoisomerase II and appears to cause DNA strand breakage. It has been shown to delay transit of cells through the S phase and arrest cells in the late S or early G2 portion of the cell cycle. Etoposide is used in combination chemotherapy for the treatment of small cell lung cancer (SCLC).

Teniposide (vm 26, Vumon)

Clinical Context:  Teniposide inhibits topoisomerase II and appears to cause DNA strand breakage, preventing mitosis. This agent is used in combination chemotherapy for the treatment of SCLC. Black box warnings for teniposide include myelosuppression and hypersensitivity reactions.

Author

Winston W Tan, MD, FACP, Associate Professor of Medicine, Mayo Medical School; Consultant and Person-in-Charge of Genitourinary Oncology-Medical Oncology, Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic Jacksonville; Vice Chairman of Education, Division of Hematology/Oncology, Mayo Clinic Florida

Disclosure: Nothing to disclose.

Coauthor(s)

Irfan Maghfoor, MD, Consulting Oncologist, Department of Oncology, King Faisal Specialist Hospital and Research Center, Saudi Arabia

Disclosure: Nothing to disclose.

Chief Editor

Nagla Abdel Karim, MD, PhD, Associate Professor of Medicine, Associate Director of Experimental Therapeutics, Division of Hematology/Oncology, University of Cincinnati Cancer Institute, Department of Internal Medicine, University of Cincinnati College of Medicine

Disclosure: Nothing to disclose.

References

  1. Boffetta P, Trichopoulos D. Cancer of the lung, larynx, and pleura. Adami H, Hunter D, Trichopoulos D, eds. Textbook of Cancer Epidemiology. 2nd ed. New York, NY: Oxford University Press; 2008. 349-67.
  2. Pietanza MC, Krug LM, Wu AJ, Kris MG, Rudin CM, Travis WD. Small Cell and Neuroendocrine Tumors of the lung. DeVita VT Jr, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology. 10th ed. Philadelphia, Pa: Wolters Kluwer Health; 2015. 536-59.
  3. Cascone T, Gold KA, Glisson BS. Small Cell Carcinoma of the Lung. Kantarjian H, Wolff R, eds. The MD Anderson Manual of Medical Oncology. 3rd ed. New York, NY: McGraw-Hill Education; 2016. 323-42.
  4. Wynder EL, Graham EA. Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma; a study of 684 proved cases. J Am Med Assoc. 1950 May 27. 143(4):329-36. [View Abstract]
  5. Pesch B, Kendzia B, Gustavsson P, Jockel KH, Johnen G,et al. Cigarette smoking and lung cancer--relative risk estimates for the major histological types from a pooled analysis of case-control studies. Int J Cancer. 2012 Sep 1. 131(5):1210-9. [View Abstract]
  6. Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ. 2010 Jan 21. 340:b5569. [View Abstract]
  7. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016 Jan-Feb. 66 (1):7-30. [View Abstract]
  8. Frank AL. Epidemiology of lung cancer. Roth JA, Ruckdeschel J, Weisenburger T, eds. Thoracic Oncology. Philadelphia, Pa: WB Saunders Co; 1989. 6-15.
  9. Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006 Oct 1. 24(28):4539-44. [View Abstract]
  10. American Cancer Society. Cancer Facts & Figures 2016. Available at http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf. Accessed: August 25, 2016.
  11. Small Cell Lung Cancer Treatment (PDQ®): Health Professional Version. National Cancer Institute. Available at http://www.ncbi.nlm.nih.gov/books/NBK65909/#CDR0000062945__1. July 7, 2016; Accessed: August 26, 2016.
  12. [Guideline] Früh M, De Ruysscher D, Popat S, Crinò L, Peters S, Felip E, et al. Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013 Oct. 24 Suppl 6:vi99-105. [View Abstract]
  13. World Health Organization. Cancer fact sheet no. 297. Updated February 2015. Available at http://www.who.int/mediacentre/factsheets/fs297/en/. Accessed: August 26, 2016.
  14. Jackman DM, Johnson BE. Small-cell lung cancer. Lancet. 2005 Oct 15-21. 366(9494):1385-96. [View Abstract]
  15. Janne PA, Freidlin B, Saxman S, Johnson DH, Livingston RB, Shepherd FA, et al. Twenty-five years of clinical research for patients with limited-stage small cell lung carcinoma in North America. Cancer. 2002 Oct 1. 95(7):1528-38. [View Abstract]
  16. Wu C, Xu B, Yuan P, Miao X, Liu Y, Guan Y, et al. Genome-wide interrogation identifies YAP1 variants associated with survival of small-cell lung cancer patients. Cancer Res. 2010 Dec 1. 70(23):9721-9. [View Abstract]
  17. Xun WW, Brennan P, Tjonneland A, Vogel U, Overvad K, el at. Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC). Mutagenesis. 2011 Sep. 26(5):657-66. [View Abstract]
  18. Hermes A, Waschki B, Reck M. Hyponatremia as prognostic factor in small cell lung cancer--a retrospective single institution analysis. Respir Med. 2012 Jun. 106(6):900-4. [View Abstract]
  19. Campling BG, Sarda IR, Baer KA, Pang SC, Baker HM, Lofters WS, et al. Secretion of atrial natriuretic peptide and vasopressin by small cell lung cancer. Cancer. 1995 May 15. 75(10):2442-51. [View Abstract]
  20. Shepherd FA, Laskey J, Evans WK, Goss PE, Johansen E, Khamsi F. Cushing's syndrome associated with ectopic corticotropin production and small-cell lung cancer. J Clin Oncol. 1992 Jan. 10(1):21-7. [View Abstract]
  21. Sher E, Gotti C, Canal N, Scoppetta C, Piccolo G, Evoli A, et al. Specificity of calcium channel autoantibodies in Lambert-Eaton myasthenic syndrome. Lancet. 1989 Sep 16. 2(8664):640-3. [View Abstract]
  22. American Cancer Society. Lung cancer (small cell): how is small cell lung cancer staged?. Available at http://www.cancer.org/cancer/lungcancer-smallcell/detailedguide/small-cell-lung-cancer-staging. 9/12/2014; Accessed: October 2, 2015.
  23. Micke P, Faldum A, Metz T, Beeh KM, Bittinger F, Hengstler JG, et al. Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer--what limits limited disease?. Lung Cancer. 2002 Sep. 37(3):271-6. [View Abstract]
  24. [Guideline] NCCN Clinical Practice Guidelines in Oncology: Small Cell Lung Cancer Vol 2. 2017. National Comprehensive Cancer Network. Available at http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. September 15, 2016; Accessed: September 25, 2016.
  25. Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010:299-330.
  26. [Guideline] National Collaborating Centre for Cancer. Lung cancer. The diagnosis and treatment of lung cancer. Publication no. 121. London, UK: National Institute for Health and Clinical Excellence; 2011.
  27. [Guideline] Wender R, Fontham ET, Barrera E Jr, Colditz GA, Church TR, Ettinger DS, et al. American Cancer Society lung cancer screening guidelines. CA Cancer J Clin. 2013 Mar-Apr. 63 (2):107-17. [View Abstract]
  28. [Guideline] Lung Cancer: Screening. U.S. Preventive Services Task Force. Available at http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/lung-cancer-screening. December 2013; Accessed: October 2, 2015.
  29. [Guideline] Detterbeck FC, Lewis SZ, Diekemper R, Addrizzo-Harris D, Alberts WM. Executive Summary: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May. 143 (5 Suppl):7S-37S. [View Abstract]
  30. [Guideline] Ung YC, Maziak DE, Vanderveen JA, Smith CA, Gulenchyn K, Evans WK, for the Lung Cancer Disease Site Group. 18-fluorodeoxyglucose positron emission tomography in the diagnosis and staging of lung cancer: a clinical practice guideline. Toronto, Ontario: Cancer Care Ontario; 2007.
  31. Thomson D, Hulse P, Lorigan P, Faivre-Finn C. The role of positron emission tomography in management of small cell lung cancer. Lung Cancer. 2011 Aug. 73(2):121-6. [View Abstract]
  32. Dresler CM, Olak J, Herndon JE 2nd, Richards WG, el at. Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion. Chest. 2005 Mar. 127(3):909-15. [View Abstract]
  33. Zakowski MF. Pathology of small cell carcinoma of the lung. Semin Oncol. 2003 Feb. 30(1):3-8. [View Abstract]
  34. Halvorsen TO, Sundstrøm S, Fløtten Ø, Brustugun OT, Brunsvig P, Aasebø U, et al. Comorbidity and outcomes of concurrent chemo- and radiotherapy in limited disease small cell lung cancer. Acta Oncol. 2016 Aug 23. 1-9. [View Abstract]
  35. Hanna NH, Einhorn LH. Small-cell lung cancer: state of the art. Clin Lung Cancer. 2002 Sep. 4(2):87-94. [View Abstract]
  36. Lally BE, Urbanic JJ, Blackstock AW, Miller AA, Perry MC. Small cell lung cancer: have we made any progress over the last 25 years?. Oncologist. 2007 Sep. 12(9):1096-104. [View Abstract]
  37. Leighl NB. Sunitinib: the next advance in small-cell lung cancer?. J Clin Oncol. 2015 May 20. 33 (15):1637-9. [View Abstract]
  38. Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, et al. Chemotherapy With or Without Maintenance Sunitinib for Untreated Extensive-Stage Small-Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase II Study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20. 33 (15):1660-5. [View Abstract]
  39. Amarasena IU, Walters JA, Wood-Baker R, Fong K. Platinum versus non-platinum chemotherapy regimens for small cell lung cancer. Cochrane Database Syst Rev. 2008 Oct 8. CD006849. [View Abstract]
  40. Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, et al. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1. 29(16):2215-22. [View Abstract]
  41. Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002 Jan 10. 346(2):85-91. [View Abstract]
  42. Jiang L, Yang KH, Guan QL, Mi DH, Wang J. Cisplatin plus etoposide versus other platin-based regimens for patients with extensive small-cell lung cancer: a systematic review and meta-analysis of randomised, controlled trials. Intern Med J. 2012 Dec. 42(12):1297-309. [View Abstract]
  43. Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1. 24(13):2038-43. [View Abstract]
  44. Schmittel A, Sebastian M, Fischer von Weikersthal L, et al. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011 Aug. 22(8):1798-804. [View Abstract]
  45. Rossi A, Di Maio M, Chiodini P, Rudd RM, Okamoto H, Skarlos DV, 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 May 10. 30(14):1692-8. [View Abstract]
  46. Klasa RJ, Murray N, Coldman AJ. Dose-intensity meta-analysis of chemotherapy regimens in small-cell carcinoma of the lung. J Clin Oncol. 1991 Mar. 9(3):499-508. [View Abstract]
  47. Arriagada R, Le Chevalier T, Pignon JP, Riviere A, Monnet I, Chomy P, et al. Initial chemotherapeutic doses and survival in patients with limited small-cell lung cancer. N Engl J Med. 1993 Dec 16. 329(25):1848-52. [View Abstract]
  48. Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, 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 Jul 15. 20(14):3054-60. [View Abstract]
  49. Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999 Jan 28. 340(4):265-71. [View Abstract]
  50. Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007 Aug 16. 357(7):664-72. [View Abstract]
  51. Schild SE, Foster NR, Meyers JP, Ross HJ, Stella PJ, et al. Prophylactic cranial irradiation in small-cell lung cancer: findings from a North Central Cancer Treatment Group Pooled Analysis. Ann Oncol. 2012 Nov. 23(11):2919-24. [View Abstract]
  52. Natale R, Lara P, Chansky K, et al. A randomized phase III trial comparing irinotecan/cisplatin (IP) with etoposide/cisplatin (EP) in patients (pts) with previously untreated extensive stage small cell lung cancer (E-SCLC). J Clin Oncol. 2008;26 (suppl):400s.
  53. Heigener D, Freitag L, Eschbach C et al. Topotecan/cisplatin (TP) compared to cisplatin/etoposide (PE) for patients with extensive disease-small cell lung cancer (ED-SCLC): final results of a randomised phase III trial. J Clin Oncol. 2008;26 (suppl):400s.
  54. Slotman BJ, van Tinteren H, Praag JO, Knegjens JL, El Sharouni SY, Hatton M, et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet. 2015 Jan 3. 385 (9962):36-42. [View Abstract]
  55. Harris S, Chan MD, Lovato JF, Ellis TL, Tatter SB, Bourland JD, et al. Gamma knife stereotactic radiosurgery as salvage therapy after failure of whole-brain radiotherapy in patients with small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2012 May 1. 83(1):e53-9. [View Abstract]
  56. GlaxoSmithKline. GSK receives approval for Hycamtin(R) (topotecan) capsules for the treatment of relapsed small cell lung cancer [press release]. October 15, 2007. Available at http://www.gsk.com/media/press-releases/2007/gsk-receives-approval-for-hycamtin-topotecan-capsules-for-the-treatment-of-relapsed-small-cell-lung-cancer.htm. Accessed: December 10, 2012.
  57. Jotte R, Conkling P, Reynolds C, Galsky MD, Klein L, Fitzgibbons JF, et al. Randomized phase II trial of single-agent amrubicin or topotecan as second-line treatment in patients with small-cell lung cancer sensitive to first-line platinum-based chemotherapy. J Clin Oncol. 2011 Jan 20. 29(3):287-93. [View Abstract]
  58. Schreiber D, Rineer J, Vongtama D, et al. Surgery for limited-stage small cell lung cancer, should the paradigm shift? A SEER-based analysis. J Clin Oncol (Suppl). 2008. 26:403s.
  59. Anraku M, Waddell TK. Surgery for small-cell lung cancer. Semin Thorac Cardiovasc Surg. 2006 Fall. 18(3):211-6. [View Abstract]
  60. [Guideline] Jaklitsch MT, Jacobson FL, Austin JH, Field JK, Jett JR, Keshavjee S, et al. The American Association for Thoracic Surgery guidelines for lung cancer screening using low-dose computed tomography scans for lung cancer survivors and other high-risk groups. J Thorac Cardiovasc Surg. 2012 Jul. 144 (1):33-8. [View Abstract]
  61. [Guideline] Rudin CM, Ismaila N, Hann CL, Malhotra N, Movsas B, Norris K, et al. Treatment of Small-Cell Lung Cancer: American Society of Clinical Oncology Endorsement of the American College of Chest Physicians Guideline. J Clin Oncol. 2015 Dec 1. 33 (34):4106-11. [View Abstract]

High-power photomicrograph of small cell carcinoma on the left side of the image with normal ciliated respiratory epithelium on the right side of the image.

High-power photomicrograph of small cell carcinoma on the left side of the image with normal ciliated respiratory epithelium on the right side of the image.

This coronal positron emission tomogram shows a large, focal, hypermetabolic area on the right that is consistent with a large mass in the central portion of the right upper pulmonary lobe. Multiple other smaller hypermetabolic areas suggest lymph-node metastatic disease in the chest, abdomen, and right supraclavicular region.