Small Cell Lung Cancer

1
Small Cell Lung Cancer

• Sam Wang

2
Outline

• Small Cell Lung Cancer

3
SCLC - Background

• SCLC Incidence
• ACS 2007 All Lung CA incidence 213000
• 13 of all lung CA (27000)

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)

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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

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Lymph Node Stations
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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

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SCLC Paraneoplastic Syndromes

• SIADH
• ectopic ACTH production- Cushings synd
• Eaton-Lambert Myasthenic syndrome
• proximal muscle weakness that improves on
  repetition (facilitation)
• Hypercalcemia
• Peripheral Neuropathy

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Workup

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

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SCLC Staging

• Limited Stage (1/3)
• confined to 1 hemithorax
• disease fits within a tolerable radiation port
• Extensive Stage (2/3)
• doesnt fit
• Recommend also use TNM staging as for NSCLC

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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

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Survival

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

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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)

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Treatment Extensive Stage

• Chemo
• RT for palliation only

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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 _at_ BID
• Lung V20
• Heart D50

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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

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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

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Turrisi - Esophagitis worse in BID arm
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Turrisi Survival
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Turrisi Overall Survival
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Turrisi Local Distant Failure

• Local Failure
• QD RT 52
• BID RT 36 (p0.06)
• Local and Distant Failure
• QD RT 23
• BID RT 6 (p0.01)

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Turrisi - Conclusions

• BID more effective than QD
• Benefit 10 absolute increase in overall
  survival _at_ 5yrs
• Cost 15 increase in high grade esophagitis

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Turrisi - Criticisms

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

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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
  _at_ 3yrs.
• Better if PCI
• No assessment of neurocognitive fxn

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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.

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Quiz
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• 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.

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• 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
• 403. 10
• A. High mediastinal.
• B. Low paratracheal.
• C. Subcarinal
• D. Hilar
• E. Subaortic

49

• 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

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.
• False
• 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