Small-cell carcinoma

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Small-cell carcinoma
Other namesSmall-cell lung cancer, or Oat-cell carcinoma
Small cell lung cancer - cytology.jpg
Micrograph of a small-cell carcinoma of the lung showing cells with nuclear moulding, minimal amount of cytoplasm and stippled chromatin. FNA specimen. Field stain.
SpecialtyOncology Edit this on Wikidata

Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung,[1] although it can occasionally arise in other body sites, such as the cervix,[2] prostate,[3] and gastrointestinal tract. Compared to non-small cell carcinoma, small cell carcinoma has a shorter doubling time, higher growth fraction, and earlier development of metastases.

10-year relative survival rate is 3.5%; however, women have higher 10-year survival rate, 4.3%, and men lower, 2.8%. [4]

Types of SCLC[edit]

Small-cell lung carcinoma has long been divided into two clinicopathological stages, including limited stage (LS) and extensive stage (ES). The stage is generally determined by the presence or absence of metastases, whether or not the tumor appears limited to the thorax, and whether or not the entire tumor burden within the chest can feasibly be encompassed within a single radiotherapy portal.[5] In general, if the tumor is confined to one lung and the lymph nodes close to that lung, the cancer is said to be LS. If the cancer has spread beyond that, it is said to be ES.

LS-SCLC[edit]

In cases of LS-SCLC, combination chemotherapy (often including cyclophosphamide, cisplatin, doxorubicin, etoposide, vincristine and/or paclitaxel) is administered together with concurrent chest radiotherapy (RT).

Chest RT has been shown to improve survival in LS-SCLC.

Exceptionally high objective initial response rates (RR) of between 60% and 90% are seen in LS-SCLC using chemotherapy alone, with between 45% and 75% of individuals showing a "complete response" (CR), which is defined as the disappearance of all radiological and clinical signs of tumor. However, relapse rate remains high, and median survival is only 18 to 24 months.

Because SCLC usually metastasizes widely very early on in the natural history of the tumor, and because nearly all cases respond dramatically to chemotherapy and/or radiotherapy, there has been little role for surgery in this disease since the 1970s.[6] However, recent work suggests that in cases of small, asymptomatic, node-negative SCLC's ("very limited stage"), surgical excision may improve survival when used prior to chemotherapy ("adjuvant chemotherapy").[7]

ES-SCLC[edit]

In ES-SCLC, platinum-based combination chemotherapy is the standard of care,[8] with radiotherapy added only to palliate symptoms such as dyspnea, pain from liver or bone metastases, or for treatment of brain metastases, which, in small-cell lung carcinoma, typically have a rapid, if temporary, response to whole brain radiotherapy.

Combination chemotherapy consists of a wide variety of agents, including cisplatin, cyclophosphamide, vincristine and carboplatin. Response rates are high even in extensive disease, with between 15% and 30% of subjects having a complete response to combination chemotherapy, and the vast majority having at least some objective response. Responses in ES-SCLC are often of short duration, and the evidence surrounding the risk of treatment compared to the potential benefit of chemotherapy for people who have extensive SCLC is not clear.[8]

If complete response to chemotherapy occurs in a subject with SCLC, then prophylactic cranial irradiation (PCI) is often used in an attempt to prevent the emergence of brain metastases. Although this treatment is often effective, it can cause hair loss and fatigue. Prospective randomized trials with almost two years follow-up have not shown neurocognitive ill-effects. Meta-analyses of randomized trials confirm that PCI provides significant survival benefits.[citation needed]

In August 2018, the FDA approved nivolumab to treat patients with metastatic small cell lung cancer (SCLC) who failed to respond to platinum-based chemotherapy and at least one other line of treatment. Nivolumab is approved in more than 60 countries. According to LUNGevity Foundation, “This approval marks a major milestone for the patients touched by this unrelenting disease and may motivate them to pursue further treatment where there previously were no other approved options.”[9]

In September 2018, the results from the global, randomized phase I/III IMpower 133 trial were announced at the World Congress on Lung Cancer in Toronto, ON. In this study, patients with ES-SCLC were treated with standard carboplatin plus etoposide and were randomized to receive atezolizumab or placebo. Atezolizumab was associated with a significant improvement in overall survival (HR for death = 0.70)[10]

Signs and symptoms[edit]

right side lung, side S2-S3 small cell carcinoma

Small-cell carcinoma of the lung usually presents in the central airways and infiltrates the submucosa leading to narrowing of bronchial airways. Common symptoms include cough, dyspnea, weight loss, and debility. Over 70% of patients with small-cell carcinoma present with metastatic disease; common sites include liver, adrenals, bone, and brain.

Due to its high grade neuroendocrine nature, small-cell carcinomas can produce ectopic hormones, including adrenocorticotropic hormone (ACTH) and anti-diuretic hormone (ADH). Ectopic production of large amounts of ADH leads to syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH).

Lambert-Eaton myasthenic syndrome (LEMS) is a well-known paraneoplastic condition linked to small-cell carcinoma.[11]

Small cell lung cancer[edit]

Histopathologic image of small-cell carcinoma of the lung. CT-guided core needle biopsy. H&E stain.

When associated with the lung, it is sometimes called "oat cell carcinoma" due to the flat cell shape and scanty cytoplasm. Caution is required when diagnosing SCLC, because small cell mesothelioma — an extremely rare subtype of lung cancer — can be mistaken for small cell lung cancer.[12]

It is thought to originate from neuroendocrine cells (APUD cells) in the bronchus called Feyrter cells (named for Friedrich Feyrter).[13] Hence, they express a variety of neuroendocrine markers, and may lead to ectopic production of hormones like ADH and ACTH that may result in paraneoplastic syndromes and Cushing's syndrome.[14] Approximately half of all individuals diagnosed with Lambert-Eaton myasthenic syndrome (LEMS) will eventually be found to have a small-cell carcinoma of the lung.[11]

Small-cell carcinoma is most often more rapidly and widely metastatic than non-small-cell lung carcinoma[15] (and hence staged differently). There is usually early involvement of the hilar and mediastinal lymph nodes. [14]

Combined small-cell lung carcinoma (c-SCLC)[edit]

Small-cell lung carcinoma can occur in combination with a wide variety of other histological variants of lung cancer,[16] including extremely complex malignant tissue admixtures.[17] [18] When it is found with one or more differentiated forms of lung cancer, such as squamous cell carcinoma or adenocarcinoma, the malignant tumor is then diagnosed and classified as a combined small cell lung carcinoma (c-SCLC).[16] C-SCLC is the only currently recognized subtype of SCLC.[16]

Although combined small-cell lung carcinoma is currently staged and treated similarly to "pure" small-cell carcinoma of the lung, recent research suggests surgery might improve outcomes in very early stages of this tumor type.

Smoking is a significant risk factor.

Symptoms and signs are as for other lung cancers. In addition, because of their neuroendocrine cell origin, small-cell carcinomas will often secrete substances that result in paraneoplastic syndromes such as Lambert-Eaton myasthenic syndrome.

Extrapulmonary small-cell carcinoma[edit]

Very rarely, the primary site for small-cell carcinoma is outside of the lungs and pleural space; in these cases, it is referred to as extrapulmonary small-cell carcinoma (EPSCC). Outside of the respiratory tract, small-cell carcinoma can appear in the cervix, prostate, liver, pancreas, gastrointestinal tract, or bladder.[19] It is estimated to account for 1,000 new cases a year in the U.S. Histologically similar to small-cell lung cancer, therapies for small-cell lung cancer are usually used to treat EPSCC.[20] First-line treatment is usually with cisplatin and etoposide. In Japan, first-line treatment is shifting to irinotecan and cisplatin.

When the primary site is in the skin, it is referred to as a Merkel-cell carcinoma.

Extrapulmonary small-cell carcinoma localized in the lymph nodes[edit]

This is an extremely rare type of small cell, and there has been little information in the scientific community. It appears to occur in only one or more lymph nodes, and nowhere else in the body. Treatment is similar to small cell lung cancer, but survival rates are much higher than other small-cell carcinomas.[21]

Small-cell carcinoma of the prostate[edit]

In the prostate, small-cell carcinoma (SCCP) is a rare form of cancer (approx 1% of PC).[22] Due to the fact that there is little variation in prostate specific antigen levels, this form of cancer is normally diagnosed at an advanced stage, after metastasis.

It can metastasize to the brain.[23]

Genetics[edit]

TP53 is mutated in 70 to 90% of SCLCs. RB1 and the retinoblastoma pathway are inactivated in most SCLCs. PTEN is mutated in 2 to 10%. MYC amplifications and amplification of MYC family members are found in 30% of SCLCs. Loss of heterozygocity on chromosome arm 3p is found in more than 80% of SCLCs, including the loss of FHIT.[24] One hundred translocations have so far been reported in SCLCs (see the "Mitelman Database"[25] and the Atlas of Genetics and Cytogenetics in Oncology and Haematology,[26]).

Diagnosis[edit]

When

  • Localized: the cancer is confined to the lung (aka: limited stage SCLC).
  • Regional: the cancer has spread to lymph nodes (or glands) within the chest (between limited and extensive stage SCLC). Lymph nodes act as a filtering system outside the lung, collecting cancer cells that are beginning to migrate out of the lung.
  • Distant: the cancer has spread (or metastasized) to other parts of the body (aka: extensive stage SCLC).[27]

Small-cell carcinoma is an undifferentiated neoplasm composed of primitive-appearing cells.

As the name implies, the cells in small-cell carcinomas are smaller than normal cells, and barely have room for any cytoplasm. Some researchers identify this as a failure in the mechanism that controls the size of the cells.[28]

Treatment[edit]

Small Cell Lung Cancer is most commonly treated with a combination of 2 drugs, which is more effective than one drug alone.

Chemotherapy[edit]

  1. Cisplatin and Etoposide,
  2. Carboplatin and Etoposide.

Immunotherapy[edit]

Recently, FDA approved two immunotherapies for small cell lung cancer:

1. Opdivo (Nivolumab) [29] [30], and

2. Tecentriq (Atezolizumab) [31][32]

Radiation Therapy[edit]

Chest radiation helps SCLC patients live longer by killing cancer cells and helping prevention of cancer recurrence.[33] Another type of radiation, prophylactic cranial radiation, prevents central nervous system recurrence and can improve survival in patients with good performance status who have had a complete response or a very good partial response to chemoradiation in LD or chemotherapy in ED.[34]

In case of relapse[edit]

If small cell lung cancer comes back after treatment, the following combination of drugs may be used:[35]

  1. Cyclophosphamide (Cytoxan, Procytox),
  2. Doxorubicin (Adriamycin) and
  3. Vincristine (Oncovin)
  4. Paclitaxel (Taxol)[36]

Current guidelines recommend that patients who relapse > 6 months from initial therapy should be retreated with the original chemotherapy regimen. For patients who relapse in < 6 months, single-agent chemotherapy either topotecan second-line therapy, or paclitaxel can be used.[37]

Several newer agents, including temozolomide and bendamustine, have activity in relapsed SCLC. Of note, temozolomide yielded a response rate of 38% for brain metastases due to SCLC.[37]

Prognosis[edit]

5-year survival rates for small cell lung cancer range between 3.6% and 32.2% for women, and between 2.2% and 24.5% for men. [38] Relative 5-year survival rate for both sexes has increased from 3.6% in 1975 to 6.7% in 2014. [39]

Small-cell carcinoma is very responsive to chemotherapy and radiotherapy, and in particular, regimens based on platinum-containing agents. However, most people with the disease relapse, and median survival remains low. The overall incidence and mortality rates of SCLC in the United States have decreased during the past few decades.[40]

Pie chart showing incidence of small-cell lung cancer (shown in red at right), as compared to other lung cancer types, with fractions of smokers versus non-smokers shown for each type.[41]

In limited-stage disease, relative 5-year survival rate (both sexes, all races, all ages) is 21.3%; however, women have higher 5-year survival rates, 26.9%, and men have lower survival rates, 21.3%. [42]

The prognosis is far more grim in extensive-stage small-cell lung carcinoma where 5-year relative survival rate (both sexes, all races, all ages) is 2.8%; however, women have higher 5-year survival rates, 3.4%, and men have lower 5-year survival rates, 2.2%.[43]

Long term survival of more than 5 years can be achieved with proper treatment. According to the 17th World Conference on Lung Cancer (WCLC), "patients who received chest radiation and prophylactic cranial irradiation along with a mean of five chemotherapy cycles could achieve a median survival of more than 5 years."[44] [45]

In some cases, long term survival of 10+ years is achieved with chemotherapy and radiation alone.[46][47]

5-year Survival Rates[edit]

The SEER database tracks 5-year relative survival rates based on age, gender, and race and is considered the most accurate source of survival information.[48] This database uses terms "Localized," "Regional," and "Distant" to describe various stages of small cell lung cancer.

5-year relative survival rate for "both sexes" and "all races" affected by

  • "Localized" small cell lung cancer is 28.5%;
  • "Regional" small cell lung cancer 14.9%; and for
  • "Distant" small cell lung cancer 2.9%.[49]

Survival Rates by Gender[edit]

Women affected by small-cell lung cancer tend to have higher 5-year survival rates than men. [50]

  • Localized: Women — 32.20% | Men — 24.50%
  • Regional: Women — 17.0% | Men — 12.30%
  • Distant: Women — 3.60% | Men — 2.20%

Survival Rates by Race, Gender, Age[edit]

5-year relative survival statistics are more accurate and in some cases higher when specific Race & Age range are combined with Gender and Stage at Diagnosis. For example,

  • Black / Female | Ages < 50 (at diagnosis) | Distant (ES SCLC) | = 7.00%.[51]
  • White / Female | Ages < 50 (at diagnosis) | Distant (ES SCLC) | = 6.10% [52]

National Cancer Institute's SEER maintains publicly accessible database for specific survival rates. [53]

Epidemiology[edit]

15% of lung cancers in the US are of this type.[54] Small cell lung cancer occurs almost exclusively in smokers; most commonly in heavy smokers and rarely in non-smokers.[55][56] According to available data, slightly more than 50% of all lung cancer types is caused by factors other than active smoking and occurs in never smokers.[57] About half of patients who are diagnosed with lung cancer have either never smoked (15%) or are former smokers (35%) who quit long time ago.[58]

Recalcitrant Cancer Research Act[edit]

In 2013, Congress passed the Recalcitrant Cancer Research Act, which mandated increased attention to certain recalcitrant cancers, including small cell lung cancer. That led to the National Cancer Institute supporting small cell–specific research through a consortium.

As a result, new experimental drugs for small cell lung cancer are currently being tested, including Iadademstat (ORY-1001) and Keytruda (pembrolizumab). [59][60][61][62]

Additional images[edit]

See also[edit]

References[edit]

  1. ^ "small-cell carcinoma" at Dorland's Medical Dictionary
  2. ^ Nasu K, Hirakawa T, Okamoto M, et al. (2011). "Advanced small cell carcinoma of the uterine cervix treated by neoadjuvant chemotherapy with irinotecan and cisplatin followed by radical surgery". Rare Tumors. 3 (1): 18–20. doi:10.4081/rt.2011.e6. PMC 3070456. PMID 21464879.
  3. ^ Capizzello A, Peponi E, Simou N, et al. (2011). "Pure small cellliterature review". Case Rep Oncol. 4 (1): 88–95. doi:10.1159/000324717. PMC 3072185. PMID 21475596.
  4. ^ [https://seer.cancer.gov/explorer/application.php?site=611&data_type=4&graph_type=6&compareBy=stage&chk_sex_1=1&chk_race_1=1&chk_age_range_1=1&chk_stage_101=101&advopt_precision=1&showDataFor=sex_1_and_race_1_and_age_range_1 SEER Cancer Stats (2016) | https://seer.cancer.gov/explorer/application.php?site=611&data_type=4&graph_type=6&compareBy=stage&chk_sex_1=1&chk_race_1=1&chk_age_range_1=1&chk_stage_101=101&advopt_precision=1&showDataFor=sex_1_and_race_1_and_age_range_1
  5. ^ Argiris A, Murren JR (2001). "Staging and clinical prognostic factors for small-cell lung cancer". Cancer J. 7 (5): 437–47. PMID 11693903.
  6. ^ Mountain CF (September 1978). "Clinical biology of small cell carcinoma: relationship to surgical therapy". Semin. Oncol. 5 (3): 272–9. PMID 211638.
  7. ^ Shepherd FA (February 2010). "Surgery for limited stage small cell lung cancer: time to fish or cut bait". J Thorac Oncol. 5 (2): 147–9. doi:10.1097/JTO.0b013e3181c8cbf5. PMID 20101141.
  8. ^ a b Pelayo Alvarez, Marta; Westeel, Virginie; Cortés-Jofré, Marcela; Bonfill Cosp, Xavier (27 November 2013). "Chemotherapy versus best supportive care for extensive small cell lung cancer". Cochrane Database of Systematic Reviews (11): CD001990. doi:10.1002/14651858.CD001990.pub3. PMID 24282143.
  9. ^ Immuno-Oncology News, "FDA Approves Opdivo for Certain Patients with Advanced Small Cell Lung Cancer" | https://immuno-oncologynews.com/2018/08/21/immunotherapy-opdivo-fda-approved-some-small-cell-lung-cancer-patients/
  10. ^ Horn, Leora; Mansfield, Aaron S.; Szczęsna, Aleksandra; Havel, Libor; Krzakowski, Maciej; Hochmair, Maximilian J.; Huemer, Florian; Losonczy, György; Johnson, Melissa L.; Nishio, Makoto; Reck, Martin; Mok, Tony; Lam, Sivuonthanh; Shames, David S.; Liu, Juan; Ding, Beiying; Lopez-Chavez, Ariel; Kabbinavar, Fairooz; Lin, Wei; Sandler, Alan; Liu, Stephen V. (6 December 2018). "First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer". New England Journal of Medicine. 379 (23): 2220–2229. doi:10.1056/NEJMoa1809064. PMID 30280641.
  11. ^ a b Titulaer MJ, Verschuuren JJ (2008). "Lambert-Eaton myasthenic syndrome: tumor versus nontumor forms". Ann. N. Y. Acad. Sci. 1132 (1): 129–34. Bibcode:2008NYASA1132..129T. doi:10.1196/annals.1405.030. PMID 18567862.
  12. ^ The Mesothelioma Center | https://www.asbestos.com/mesothelioma/small-cell/
  13. ^ Champaneria MC, Modlin IM, Kidd M, Eick GN (2006). "Friedrich Feyrter: a precise intellect in a diffuse system". Neuroendocrinology. 83 (5–6): 394–404. doi:10.1159/000096050. PMID 17028417.
  14. ^ a b Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). "Ch. 13, box on morphology of small-cell lung carcinoma". Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. ISBN 978-1-4160-2973-1.
  15. ^ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. p. 759. ISBN 978-0-7216-0187-8.
  16. ^ a b c Travis, William D; Brambilla, Elisabeth; Muller-Hermelink, H Konrad; et al., eds. (2004). Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart (PDF). World Health Organization Classification of Tumours. Lyon: IARC Press. ISBN 978-92-832-2418-1. Archived (PDF) from the original on 23 August 2009. Retrieved 27 March 2010.
  17. ^ Pelosi G, Sonzogni A, Galetta D, et al. (April 2011). "Combined small-cell carcinoma of the lung with quadripartite differentiation of epithelial, neuroendocrine, skeletal muscle, and myofibroblastic type". Virchows Arch. 458 (4): 497–503. doi:10.1007/s00428-010-1011-8. PMID 21210145.
  18. ^ Gotoh M, Yamamoto Y, Huang CL, Yokomise H (November 2004). "A combined small cell carcinoma of the lung containing three components: small cell, spindle cell and squamous cell carcinoma". Eur J Cardiothorac Surg. 26 (5): 1047–9. doi:10.1016/j.ejcts.2004.08.002. PMID 15519208.
  19. ^ Ismaili N (November 2011). "A rare bladder cancer – small cell carcinoma: review and update". Orphanet Journal of Rare Diseases. 6 (75): 75. doi:10.1186/1750-1172-6-75. PMC 3253713. PMID 22078012.
  20. ^ Extrapulmonary Small Cell Carcinoma at eMedicine
  21. ^ Cicin, Irfan; Usta, Ufuk; Karagol, Hakan; Uzunoglu, Sernaz; Kocak, Zafer (2009). "Extrapulmonary small cell carcinoma localized in lymph nodes: Is it a different clinical entity?". Acta Oncologica. 48 (3): 354–360. doi:10.1080/02841860802495370. PMID 18979286.
  22. ^ Nutting C, Horwich A, Fisher C, Parsons C, Dearnaley DP (June 1997). "Small-cell carcinoma of the prostate". Journal of the Royal Society of Medicine. 90 (6): 340–1. doi:10.1177/014107689709000615. PMC 1296316. PMID 9227387.
  23. ^ Erasmus CE, Verhagen WI, Wauters CA, van Lindert EJ (November 2002). "Brain metastasis from prostate small-cell carcinoma: not to be neglected". Can J Neurol Sci. 29 (4): 375–7. doi:10.1017/S0317167100002250. PMID 12463494.
  24. ^ "Lung: Translocations in Small Cell Carcinoma". atlasgeneticsoncology.org. Archived from the original on 30 January 2015. Retrieved 30 April 2018.
  25. ^ "Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer". Archived from the original on 2016-05-29.
  26. ^ "Atlas of Genetics and Cytogenetics in Oncology and Haematology". atlasgeneticsoncology.org. Archived from the original on 2011-02-23.
  27. ^ Lung Cancer - Cleveland Clinic | https://my.clevelandclinic.org/health/diseases/4375-lung-cancer
  28. ^ Leslie M (November 2011). "Mysteries of the cell. How does a cell know its size?". Science. 334 (6059): 1047–8. doi:10.1126/science.334.6059.1047. PMID 22116854.
  29. ^ "FDA Approves Opdivo for Small Cell Lung Cancer Treatment"
  30. ^ FDA Approves Opdivo (Nivolumab) for Small Cell Lung Cancer | https://www.cancer.org/latest-news/fda-approves-opdivo-nivolumab-for-small-cell-lung-cancer.html
  31. ^ FDA approves atezolizumab for extensive-stage small cell lung cancer | https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm633814.htm
  32. ^ Concurrent Tecentriq Adds First Survival Benefit Seen in Small Cell Lung Cancer in 20 Years | https://www.curetoday.com/articles/concurrent-tecentriq-adds-first-survival-benefit-seen-in-small-cell-lung-cancer-in-20-years
  33. ^ https://www.cancer.org/latest-news/study-chest-radiation-helps-small-cell-lung-cancer-patients-live-longer.html
  34. ^ https://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq
  35. ^ [[Treatment for Small Cell Lung Cancer, Canadian Cancer Society | http://www.cancer.ca/en/cancer-information/cancer-type/lung/treatment/treatment-for-small-cell-lung-cancer/?region=nu
  36. ^ Mouri, Atsuto; Yamaguchi, Ou; Miyauchi, Sachiko; Shiono, Ayako; Utsugi, Harue; Nishihara, Fuyumi; Murayama, Yoshitake; Kagamu, Hiroshi; Kobayashi, Kunihiko (January 2019). "Combination therapy with carboplatin and paclitaxel for small cell lung cancer". Respiratory Investigation. 57 (1): 34–39. doi:10.1016/j.resinv.2018.09.004. PMID 30528688.
  37. ^ a b Qin, Angel; Kalemkerian, Gregory P. (June 2018). "Treatment Options for Relapsed Small-Cell Lung Cancer: What Progress Have We Made?". Journal of Oncology Practice. 14 (6): 369–370. doi:10.1200/JOP.18.00278. PMID 29894661.
  38. ^ the SEER Cancer Statistics Review 1975-2015 | https://seer.cancer.gov/csr/1975_2015/browse_csr.php?sectionSEL=15&pageSEL=sect_15_table.13
  39. ^ https://seer.cancer.gov/archive/csr/1975_2015/browse_csr.php?sectionSEL=15&pageSEL=sect_15_table.13
  40. ^ [[https://www.oncolink.org/healthcare-professionals/nci/pqid-CDR00000629452 | National Cancer Institute: Small Cell Lung Cancer Treatment
  41. ^ Smokers defined as current or former smoker of more than 1 year of duration. See image page in Commons for percentages in numbers. Reference:
  42. ^ [2016 Cancer Stats by SEER | https://seer.cancer.gov/explorer/application.php?site=611&data_type=4&graph_type=6&compareBy=stage&chk_sex_2=2&chk_race_1=1&chk_age_range_1=1&chk_stage_104=104&advopt_precision=1&showDataFor=sex_2_and_race_1_and_age_range_1
  43. ^ [2016 Cancer Stats by SEER | https://seer.cancer.gov/explorer/application.php?site=611&data_type=4&graph_type=6&compareBy=stage&chk_sex_2=2&chk_race_1=1&chk_age_range_1=1&chk_stage_104=104&advopt_precision=1&showDataFor=sex_2_and_race_1_and_age_range_1
  44. ^ Medscape "Exceptional SCLC Survivors: 5-Year Median Survival", Dec 20, 2016. | https://www.medscape.com/viewarticle/873492
  45. ^ the SEER Cancer Statistics Review 1975-2015 | https://seer.cancer.gov/csr/1975_2015/browse_csr.php?sectionSEL=15&pageSEL=sect_15_table.13
  46. ^ https://www.self.com/story/lung-cancer
  47. ^ Extensive Stage SCLC survivor Montessa M. Lee was presenting during 2019 IASLC | https://www.iaslc.org/news/focus-immunotherapy-and-patient-perspective-highlight-iaslc-2019-small-cell-lung-cancer-meetin]]
  48. ^ 5-Year Relative Survival (Percent) 2008-2014 by Stage at Diagnosis | https://seer.cancer.gov/csr/1975_2015/browse_csr.php?sectionSEL=15&pageSEL=sect_15_table.13#table5
  49. ^ the SEER Cancer Statistics Review 1975-2015 | https://seer.cancer.gov/csr/1975_2015/browse_csr.php?sectionSEL=15&pageSEL=sect_15_table.13
  50. ^ "Browse the Tables and Figures - SEER Cancer Statistics Review (CSR) 1975-2015".
  51. ^ [SEER Database, Cancer Survival Rates | https://seer.cancer.gov/explorer/application.php?site=611&data_type=4&graph_type=5&compareBy=age_range&series=sex&chk_sex_3=3&chk_race_3=3&chk_age_range_9=9&chk_stage_106=106&advopt_precision=1&advopt_show_se=on&advopt_show_ci=on&showDataFor=race_3_and_stage_106]
  52. ^ [SEER Database, Cancer Survival Rates | https://seer.cancer.gov/explorer/application.php?site=611&data_type=4&graph_type=5&compareBy=age_range&series=sex&chk_sex_3=3&chk_race_8=8&chk_age_range_9=9&chk_stage_106=106&advopt_precision=1&advopt_show_se=on&advopt_show_ci=on&showDataFor=race_8_and_stage_106]
  53. ^ [SEER Small Cell Lung Cancer Survival Rates | https://seer.cancer.gov/explorer/application.php?site=611&data_type=4&graph_type=6&compareBy=stage&chk_sex_3=3&chk_race_1=1&chk_age_range_1=1&chk_stage_101=101&advopt_precision=1&showDataFor=sex_3_and_race_1_and_age_range_1]
  54. ^ World Cancer Report 2014. World Health Organization. 2014. pp. Chapter 5.1. ISBN 978-9283204299.
  55. ^ Ettinger, DS; Aisner, J (1 October 2006). "Changing face of small-cell lung cancer: real and artifact". Journal of Clinical Oncology. 24 (28): 4526–7. doi:10.1200/jco.2006.07.3841. PMID 17008688.
  56. ^ Muscat, JE; Wynder, EL (6 January 1995). "Lung cancer pathology in smokers, ex-smokers and never smokers". Cancer Letters. 88 (1): 1–5. doi:10.1016/0304-3835(94)03608-l. PMID 7850764.
  57. ^ Samet, J. M.; Avila-Tang, E.; Boffetta, P.; Hannan, L. M.; Olivo-Marston, S.; Thun, M. J.; Rudin, C. M. (14 September 2009). "Lung Cancer in Never Smokers: Clinical Epidemiology and Environmental Risk Factors". Clinical Cancer Research. 15 (18): 5626–5645. doi:10.1158/1078-0432.CCR-09-0376. PMC 3170525. PMID 19755391.
  58. ^ Lung Cancer Canada | http://www.lungcancercanada.ca/Lung-Cancer.aspx
  59. ^ Fred Hutch "A new focus on small cell lung cancer" | https://www.fredhutch.org/en/news/center-news/2019/02/q-a-with-david-macpherson-lung-cancer.html
  60. ^ Augert, Arnaud; Eastwood, Emily; Ibrahim, Ali H.; Wu, Nan; Grunblatt, Eli; Basom, Ryan; Liggitt, Denny; Eaton, Keith D.; Martins, Renato; Poirier, John T.; Rudin, Charles M.; Milletti, Francesca; Cheng, Wei-Yi; Mack, Fiona; MacPherson, David (5 February 2019). "Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition". Science Signaling. 12 (567): eaau2922. doi:10.1126/scisignal.aau2922. PMC 6530478. PMID 30723171.
  61. ^ Oryzon Genomics "ORY-1001 - Patient Info" | https://www.oryzon.com/en/patient/patient-information
  62. ^ Cure Magazine "Keytruda Shows Benefit in Small Cell Lung Cancer" | https://www.curetoday.com/articles/keytruda-shows-benefit-in-small-cell-lung-cancer

Washington, C. and Leaver, D. 2010. Principles and practice of radiation therapy. P 673. St. Louis, Mo.: Mosby Elsevier.

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