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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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Outline l.jpg
Outline

  • Small Cell Lung Cancer


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SCLC - Background

  • SCLC Incidence:

    • ACS 2007: All Lung CA incidence: 213,000

    • 13% of all lung CA (~27,000)


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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


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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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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- Cushing’s 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)

    • doesn’t 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%)


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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 @ BID: <36Gy

  • Lung V20 < 20-30%

  • Heart D50 < 25-40Gy


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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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2 y

5 y

Turrisi – Survival



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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)


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Turrisi - Conclusions

  • BID more effective than QD

    • Benefit: 10% absolute increase in overall survival @ 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% @ 3yrs.

  • Better if PCI <4mo from chemo start

  • 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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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


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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


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Which of the following statements does following patient presentations would be classified as limited-stage small cell lung cancer?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 following patient presentations would be classified as limited-stage small cell lung cancer?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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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.


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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.


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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


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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


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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.


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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.


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Which of the following symptoms is most common in patients presenting with primary tracheal malignancies?

A.Dyspnea

B. Hemoptysis

C. Hoarseness

D. Pneumonia


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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


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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.


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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.


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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


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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


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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


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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


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Regarding lung cancer patients: (True or False?) below:

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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Regarding lung cancer patients: (True or False?) below:

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


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