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Small Cell Lung Cancer

Small Cell Lung Cancer. Sam Wang. Outline. Small Cell Lung Cancer. SCLC - Background. SCLC Incidence: ACS 2007: All Lung CA incidence: 213,000 13% of all lung CA (~27,000). Natural History of SCLC.

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Small Cell Lung Cancer

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  1. Small Cell Lung Cancer Sam Wang

  2. Outline • Small Cell Lung Cancer

  3. SCLC - Background • SCLC Incidence: • ACS 2007: All Lung CA incidence: 213,000 • 13% of all lung CA (~27,000)

  4. Natural History of SCLC • SCLC is distinguished from NSCLC by its rapid doubling time, high growth fraction, and the early development of widespread metastases • Although considered highly responsive to chemotherapy and radiotherapy, SCLC usually relapses within two years despite treatment • Overall, only three to eight percent of all patients with SCLC (10 to 13 percent of those with limited disease) survive beyond five years

  5. SCLC Histology • SCLC is a “small blue round cell tumor” from neuroendocrine cells • Classifications: • oat cell (lymphocyte-like), fusiform, polygonal • OR classical, large cell neuroendocrine, combined SCLC/NSCLC • “crush” artifact • Immunohisto tests: • TTF1+ (adeno & SCLC)

  6. Lymph Node Stations 1 2 3a 3b 4 5 6 7 8 9 10 11-14 • highest mediastinal • upper paratracheal • pretracheal • retrotracheal • lower paratracheal • AP window • Para-Aortic (above 5) • subcarinal • esophageal • pulmonary ligament • hilar • interlobar, lobar, segmental, subsegmental

  7. Lymph Node Stations

  8. Clinical Presentation of SCLC • Smokers (almost exclusively) • Cough 75% • Hemoptysis in 50% • Dyspnea and chest pain 40% • Constitutional symptoms 10 to 15% • Clubbing 16 to 29% • pneumonia, weight loss

  9. SCLC Paraneoplastic Syndromes • SIADH • ectopic ACTH production- Cushing’s synd • Eaton-Lambert Myasthenic syndrome • proximal muscle weakness that improves on repetition (“facilitation”) • Hypercalcemia • Peripheral Neuropathy

  10. Workup • Labs: CBC, chem, LFTs, LDH • CT chest/abd/pelvis • Brain imaging (CT or MRI) (up to 30% have brain mets at presentation)

  11. SCLC Staging • Limited Stage (1/3) • confined to 1 hemithorax • disease fits within a tolerable radiation port • Extensive Stage (2/3) • doesn’t fit • Recommend also use TNM staging, as for NSCLC

  12. Where does SCLC metastasize to? “BALLS” • Brain (30%) • Adrenal (20-40%) • Liver (25%) • Lung • Skeleton (35%)

  13. Prognostic Factors • The host factors of poor performance status and weight loss • Stage (limited versus extensive). • In extensive disease, the number of organ sites involved is inversely related to prognosis • Metastatic involvement of the central nervous system, the marrow, or the liver is unfavorable compared to other sites, although these variables are confounded by the number of sites of involvement. • In most trials, women fare better than men, although the reasons for this are not known. • The presence of paraneoplastic syndromes is generally unfavorable

  14. Survival • Limited Stage: • Median OS: 14-24 months • 5-yr OS: 20% • Extensive Stage: • MedianOS: 6-11 months • 5-yr OS: 2%

  15. Treatment – Limited Stage SCLC • Concurrent chemoradiation • Chemo: cisplatin/etoposide q3wks • Radiation: 150 cGy BID to 4500 cGy (Turrisi) OR 180 QD to 50-70Gy. (54Gy?) • Sequential chemo, then RT. • If CR, then PCI • 2500/10, 3000/15, or 2400/8 • Auperin (NEJM 99)

  16. Treatment – Extensive Stage • Chemo • RT for palliation only

  17. Treatment Fields for SCLC • Cover primary disease & known positive LNs w/ 1.5-2cm margin. • Do you cover elective mediastinal nodes for SCLC? • Cord limit @ BID: <36Gy • Lung V20 < 20-30% • Heart D50 < 25-40Gy

  18. Turrisi (NEJM 340(4):265-271, 1999) “Twice-Daily Compared With Once-Daily Thoracic Radiotherapy In Limited Small-Cell Lung Cancer Treated Concurrently With Cisplatin and Etoposide”

  19. Turrisi - Methods • 419 pts (’89-’92) with LS-SCLC • Concurrent Chemo x4c (cis/etopo) q3w • Radiation • Group 1: 1.8 Gy QD to 45 Gy • Group 2: 1.5 Gy BID to 45 Gy • Bilateral mediastinal and ipsilateral hilar adenopathy • Prophylactic Cranial Irradiation if CR • 25 Gy/ 10 fx

  20. Turrisi - Esophagitis worse in BID arm

  21. 2 y 5 y Turrisi – Survival

  22. Turrisi – Overall Survival

  23. Turrisi – Local & Distant Failure • Local Failure • QD RT: 52% • BID RT: 36% (p=0.06) • Local and Distant Failure • QD RT: 23% • BID RT: 6% (p=0.01)

  24. Turrisi - Conclusions • BID more effective than QD • Benefit: 10% absolute increase in overall survival @ 5yrs • Cost: 15% increase in high grade esophagitis

  25. Turrisi - Criticisms • QD only went to 45 Gy • Fractionation still open question • New CONVERT trial: 66 Gy QD vs 45 BID • Starts Jan 2008.

  26. Auperin Meta-Analysis of PCI (NEJM 1999) • PCI for LS-SCLC if CR after chemo • Meta-analysis of 7 trials (1965-95) • Dose Fx: 800x1 to 4000/20. • Improved 3yr OS 20.7% v 15.3%. • Incidence of brain mets decreased from 58% to 33% @ 3yrs. • Better if PCI <4mo from chemo start • No assessment of neurocognitive fxn

  27. But what about PCI for ES-SCLC? • Slotman, EORTC, ASCO 2007 • RCT, 286 pts w/ ES-SCLC • If any response to chemo x4c, then randomized to +/- PCI • PCI reduced risk of symptomatic brain mets 14.6% v 40.4% at 1 yr. • Improved 1-yr OS 27.1% vs 13.3%.

  28. Quiz

  29. According to the original VA definition, which of the following patient presentations would be classified as limited-stage small cell lung cancer? A. A 3-cm left upper-lobe lung tumor and a right hilar lymph node B. A 3-cm left lower-lobe tumor with a malignant pleural effusion C. A 7-cm right upper-lobe lung tumor with a right hilar lymph node D. A 7-cm right upper-lobe lung tumor with a right anterior cervical lymph node

  30. According to the original VA definition, which of the following patient presentations would be classified as limited-stage small cell lung cancer? A. A 3-cm left upper-lobe lung tumor and a right hilar lymph node B. A 3-cm left lower-lobe tumor with a malignant pleural effusion C. A 7-cm right upper-lobe lung tumor with a right hilar lymph node D. A 7-cm right upper-lobe lung tumor with a right anterior cervical lymph node

  31. Which of the following statements does NOT describe a feature of small cell lung carcinoma? A. Most patients are smokers. B. Abundant mucin production is associated. C. Paraneoplastic syndromes are associated. D. A majority of cases have neurosecretory-type granules.

  32. Which of the following statements does NOT describe a feature of small cell lung carcinoma? A. Most patients are smokers. B. Abundant mucin production is associated. C. Paraneoplastic syndromes are associated. D. A majority of cases have neurosecretory-type granules.

  33. A patient presents with a 3-cm solitary small cell lung tumor in the right upper lobe. Results of other imaging studies are negative for metastatic or nodal disease. Mediastinal biopsy specimens are nondiagnostic. Which of the following statements about management options is FALSE? A. Surgery is contraindicated. B. Chemotherapy has a role. C. Radiation therapy may have a role. D. Concurrent chemoradiation therapy is an option.

  34. A patient presents with a 3-cm solitary small cell lung tumor in the right upper lobe. Results of other imaging studies are negative for metastatic or nodal disease. Mediastinal biopsy specimens are nondiagnostic. Which of the following statements about management options is FALSE? A. Surgery is contraindicated. B. Chemotherapy has a role. C. Radiation therapy may have a role. D. Concurrent chemoradiation therapy is an option.

  35. The addition of radiation therapy to the thorax improves survival for patients with limited-stage, small cell lung cancers. The median survival time for patients is how many months? A. 9 to 12 B. 14 to 18 C. 20 to 24 D. 26 to 30

  36. The addition of radiation therapy to the thorax improves survival for patients with limited-stage, small cell lung cancers. The median survival time for patients is how many months? A. 9 to 12 B. 14 to 18 C. 20 to 24 D. 26 to 30

  37. Which of the following statements about prophylactic cranial irradiation (PCI) for patients with small cell lung cancer is true? A. It may be considered for patients with a complete response to treatment. B. It should be delivered concurrently with chemotherapy. C. It is commonly administered at 2 Gy per fraction to 40 Gy in 4 weeks. D. There is no decrease in CNS failure for patients who receive PCI.

  38. Which of the following statements about prophylactic cranial irradiation (PCI) for patients with small cell lung cancer is true? A. It may be considered for patients with a complete response to treatment. B. It should be delivered concurrently with chemotherapy. C. It is commonly administered at 2 Gy per fraction to 40 Gy in 4 weeks. D. There is no decrease in CNS failure for patients who receive PCI.

  39. Which of the following symptoms is most common in patients presenting with primary tracheal malignancies? A.Dyspnea B. Hemoptysis C. Hoarseness D. Pneumonia

  40. Which of the following symptoms is most common in patients presenting with primary tracheal malignancies? A.Dyspnea B. Hemoptysis C. Hoarseness D. Pneumonia ??? NOT SCORED

  41. True or False: Abnormalities in p53 are moerree common in small cell lung cancer than in non-small cell lung cancer.

  42. True or False: Abnormalities in p53 are moerree common in small cell lung cancer than in non-small cell lung cancer. • TRUE

  43. When hyperfractionated radiotherapy is delivered concurrently with chemotherapy for limited stage small cell lung cancer, which one of the following is CORRECT? A. Local control is improved. B. Survival is improved. C. Brain metastasis is decreased D. Local control and survival are improved. E. Local control and survival are improved, while brain metastasis is decreased.

  44. When hyperfractionated radiotherapy is delivered concurrently with chemotherapy for limited stage small cell lung cancer, which one of the following is CORRECT? A. Local control is improved. B. Survival is improved. C. Brain metastasis is decreased D. Local control and survival are improved. E. Local control and survival are improved, while brain metastasis is decreased.

  45. In small cell lung cancer, the use of prophylactic cranial irradiation (PCI) for patients with a complete response to induction therapy has been shown to improve the absolute overall survival by which one of the following? A. 9.1% at 5 years B. 9.8% at 3 years C. 7.4% at 5 years D. 5.4% at 3 years E. 10.1% at 7 years

  46. In small cell lung cancer, the use of prophylactic cranial irradiation (PCI) for patients with a complete response to induction therapy has been shown to improve the absolute overall survival by which one of the following? A. 9.1% at 5 years B. 9.8% at 3 years C. 7.4% at 5 years D. 5.4% at 3 years E. 10.1% at 7 years

  47. Identify each of the nodal stations for lung cancers listed below: 401. 4 402. 7 403. 10 A. High mediastinal. B. Low paratracheal. C. Subcarinal D. Hilar E. Subaortic

  48. Identify each of the nodal stations for lung cancers listed below: 401. 4 Low paratracheal 402. 7 Subcarinal 403. 10 Hilar A. High mediastinal. B. Low paratracheal. C. Subcarinal D. Hilar E. Subaortic

  49. Regarding lung cancer patients: (True or False?) 404. The most common second cancer for non-small cell lung cancer patients is lymphoma. False 405. The most common second cancer for small cell lung cancer patients is liver cancer. False 406. The incidence rate for non-smell cell lung cancer patients developing another lung cancer is 1-2% per year. True

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