1. Small Cell Lung Cancer
Sam Wang

2. Outline
Small Cell Lung Cancer

3. SCLC Incidence: SCLC - Background
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

9. 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

10. 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

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

12. Recommend also use TNM staging, as for NSCLC
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

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

14. 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

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

16. 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)

17. Treatment – Extensive Stage
Chemo
RT for palliation only

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

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

20. 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

21. Turrisi - Esophagitis worse in BID arm

22. Turrisi – Survival
2 y
5 y

23. Turrisi – Overall Survival
P=0.04
2-year
5-year
Daily
41%
16%
Twice-daily
47%
26%

24. 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)

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

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

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

28. 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%.

29. Quiz

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. 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

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. 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.

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. 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.

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. 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

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 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.

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

41. 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

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

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

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. 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.

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. 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

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

49. Identify each of the nodal stations for lung cancers listed below:
Low paratracheal
Subcarinal
Hilar
A. High mediastinal.
B. Low paratracheal.
C. Subcarinal
D. Hilar
E. Subaortic

50. 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.
406. The incidence rate for non-smell cell lung cancer patients developing another lung cancer is 1-2% per year.
True

51. Regarding lung cancer patients: (True or False?)
407. To treat the second primary lung cancer, surgery is not a viable modality.
False
408. Aerodigestive cancers do occur among smokers who have lung cancers.
True