Brief Description of Epidemiology, Pathophysiology, Staging and Management of Small Cell Lung Cancer

1. Small Cell Lung Cancer
Dr. Yogesh Belagali MD
Medical Advisor- Oncotherapeutics

2. Index
• Introduction
• Epidemiology
• Pathophysiology
• Staging System
• Management of Limited Stage Disease
– Chemotherapy
– Radiotherapy
• Management of Extensive Stage Disease
– Chemotherapy
– Radiotherapy
• Summary

3. Introduction
• Most common cancer worldwide
– Estimated 1,600,000 new cases
– 1,380,000 deaths/year
• The term lung cancer, or bronchogenic
carcinoma, refers to malignancies that
originate in the airways or pulmonary
parenchyma.

4. Indian Scenario:2012
http://globocan.iarc.fr/Pages/fact_sheets_population.aspx
Cancer Incidence Mortality 5-year prevalence
Number (%)
ASR (W
)
Number (%)
ASR (W
)
Number (%) Prop.
Lung 70275 6.9 6.9 63759 9.3 6.3 32464 1.8 3.7
Incidence:
•Male: 11/1,00,000 (most
common)
•Female: 3.1/1,00,000 ( 4th )

5. Histology

6. NSCLC vs SCLC
NSCLC SCLC
Incidence 80% 16%
Origin Epithelial cells of the lung Nerve producing cells of the lung (bronchi)
Classification  Squamous cell
 Large cell
 Adenocarcinoma
 Limited stage
 Extensive stage
Metastatic
potential
Less than SCLC Rapid metastatic potential
Treatment  Surgery
 Chemotherapy
 Radiotherapy
 Chemotherapy
 Radiotherapy
5 year survival  Stage I : 57 – 67%
 Stage II : 39 – 55%
 Stage III : 5 – 25%
 Stage IV : < 1%
 Limited 20%
 Extensive < 1%

7. 5 Year Survival Rates – By Stage
• Non-Small Cell
Lung Cancer
• IA 58-73%
• IB 43-58%
• IIA 36-46%
• IIB 25-36%
• IIIA 19-24%
• IIIB 7-9%
• IV 2-13%
• Small Cell Lung
Cancer
• Limited 18-38%
• Extensive 1%

8. Patho physiology
• Small cells with scant
cytoplasm
• Ill- defined cell borders
• Finely granular nuclear
chromatin
• Absent or inconspicuous
nucleoli
• Extensive Necrosis
• High mitotic count

9. Staging system
• To determine whether thoracic radiation
should be incorporated in conjunction with
chemotherapy for localized disease
• Two types of classification
– The tumour-node-metastases (TNM)
classification
– The VA Lung Study Group (VALSG) limited
disease- extensive stage (LD-ED) system.
• Most Commonly used

10. • Limited stage disease (LD)
– Confined to the ipsilateral hemithorax
– All known disease can be encompassed within
a single radiation port
• Extensive stage disease (ED)
– Disease in the contralateral hemithorax and
distant metastases
Staging system

11. Management of Limited Stage
Disease

12. Limited Stage Disease
• Chemoradiotherapy is indicated as the
initial treatment.
• Four cycles of chemotherapy is the
mainstay of treatment for patients with
SCLC
• In addition to chemotherapy, there is a
significant role for radiation therapy (RT)

13. Chemotherapy
• Current Standard Regimen
– Cisplatin 80 mg/m2 IV on day 1
– Etoposide 1000 mg/m2 IV on day 1,2 & 3
•
• 21 day Cycle for Four Cycles

14. Other Chemotherapy Regimens
• Irinotectan + Cisplatin
• Paclitaxel + Etoposide + Carboplatin
• Carboplatin+ Etoposide + Vincristine for 6
cycles

15. • The timing of radiotherapy is best when it
is used concurrently with chemotherapy
early after the beginning of treatment
• 5-year survival rate of about 20% has
been reported for LD cases.
• Recommended dose: 45Gy twice daily
1.5Gy fractions over 3 weeks (accelerated
hyperfractionation)
Thoracic Radiotherapy

16. Thoracic radiotherapy
• Delivery at the second cycle of
chemotherapy
• For patients with either a PS or very bulky
disease, delay the initiation of RT until
the third cycle of chemotherapy

17. Role of PET in LD
• PET may have a role in designing radiation
treatment volumes
• PET- based involved nodal radiation results
in a low rate of isolated nodal failures (3%),
with a low percentage of acute esophagitis

18. Prophylactic cranial irradiation
(PCI)
• Used for the purpose of controlling
microscopic brain metastases in the
treatment of SCLC
• Rate of brain metastasis is significantly
reduced by PCI

19. PCI- Clinical Facts
• 2-year rate of brain metastasis decreases
from 67% in the control group to 40% in
PCI group (p<10 -13 )
• 2-year cumulative rate of brain metastasis
as an isolated first site of relapse decreased
from 45% to 19% (p<10 -6 )
• 2-year rate of OS increased from 21.5% to
29% in the control group (P=0.14).
Arriagada R, Le Chevalier T, Borie F, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer
in complete remission. J Natl Cancer Inst. 1995;87(3):183-190.

20. • Meta-analysis on 987 patients with SCLC
– PCI was associated with an absolute decrease
of 25.3% in the cumulative incidence of brain
metastasis at 3 years
– An absolute increase in OS of 5.4% at 3 years
• PCI has become standard practice for
patients with SCLC who have complete
remission after chemo radiotherapy of the
primary thoracic tumor
PCI- Clinical Facts
Auperin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in
complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med.
1999;341(7):476-484.

21. Recommended dose for PCI
• The standard dose of PCI should be 25
Gy in 10 fractions within 2 weeks
• A dose of 30 Gy over 3 weeks may be an
acceptable alternative

22. Extensive Stage Disease
• Systemic chemotherapy- Primary Modality
• Prophylactic cranial irradiation - in patients
who have responded to systemic
chemotherapy
• Thoracic radiation – increas3 the percentage
of long-term survivors.

23. Management of Extensive
Stage Disease

24. • Median survival for patients with ES-SCLC
is about 8 to 13 months
• Less than 5 percent of those with ES-SCLC
survive beyond two years

25. Chemotherapeutic Regimens
used in ED
• Platinum plus etoposide
– Cisplatin plus etoposide (PE)
– Carboplatin plus etoposide (CE)
• Cisplatin plus irinotecan
– Cisplatin (60 mg/m2 on day 1) plus irinotecan
(60 mg/m2 on days 1, 8, and 15) every four
weeks
– Significantly higher response rate compared
with the etoposide-based regimen (84 versus 68
%), longer median survival (12.8 versus 9.4
months)

26. • Carboplatin plus irinotecan
• Topotecan plus cisplatin
• Epirubicin plus cisplatin
• Paclitaxel + Cisplatin + Etoposide
Chemotherapeutic Regimens
used in ED

27. • Four Drug Regimen
– Etoposide (100 mg/m2 on days 1 to 3) plus
– Cisplatin (100 mg/m2 on day 2)
– Cyclophosphamide (400 mg/m2 on days 1 to 3)
– Epirubicin (40 mg/m2 on day 1)
• Administered every four weeks for six courses
• Significant increases in response rate (76
versus 61%) and survival (median 10.5 versus
9.3 months and one-year 40 versus 29 %)
Chemotherapeutic Regimens
used in ED

28. Thoracic Radiotherapy for ES-
SCLC
• Role of TRT in ES-SCLC is unclear
• It is typically not considered part of the
standard of care
• Some preliminary evidence suggests that
adding TRT to chemotherapy improves the
survival of patients with ES-SCLC
• PCI is recommended

29. Summary of SCLC Management
• T1N0, pathologic stage T1-T2N0 limited-
stage disease
– lobectomy and nodal dissection or nodal
sampling, followed by
– Chemotherapy, followed by
– PCI

30. • Nodal positive LS-SCLC (cT-1-4pN1-
3M0)
– Concurrent TRT.
– PCI should be recommended for patients with
good treatment response
– TRT should start concurrently during the 1st or
2nd cycle of chemotherapy
– 45 Gy given in BID 1.5 Gy fractions is the
preferred regimen
Summary of SCLC Management

31. • ES-SCLC
– TRT may be recommended in patients after
4-6 cycles of chemotherapy,
– Particularly when PCI is planned, and local
thoracic disease is remarkable, or causing local
symptoms
– 30-54 Gy in 2-3 Gy daily is the preferred
regimen.
Summary of SCLC Management