Small cell lung cancer (SCLC) is an aggressive form of lung cancer associated with smoking. It is highly responsive to chemotherapy but has a high relapse rate and poor prognosis. SCLC is classified into limited stage, which can be treated with radiation, or extensive stage, which has spread. Treatment involves chemotherapy, often with cisplatin and etoposide, and concurrent radiation therapy for limited stage disease. Despite initial response, SCLC often recurs, necessitating additional chemotherapy regimens. Supportive care focuses on smoking cessation and management of paraneoplastic syndromes. Prognosis remains poor due to the aggressiveness of SCLC.

1. Small Cell Lung
Cancer
DR. MYAT SU AUNG
Radiation Oncology Department
Yangon General Hospital

2. Epidemiology
• aggressive subset of neuroendocrine tumors (NETs)
• 15% to 20% of all lung carcinomas
• More than 95% of cases are associated with a history of
tobacco exposure
• Multimodality therapy in SCLC improves survival
• SCLC is highly responsive to chemotherapy,
• But unfortunately exhibits a high rate of relapse and thus poor
prognosis.

3. Pathology
Three groups:
1. Classical small cell carcinoma
2. Large cell neuroendocrine tumor
3. Combination of small cell carcinoma, with areas of non–small
cell lung carcinoma (NSCLC)

4. • Cellular morphology under light microscopy shows small round
blue cells with scant cytoplasm, fine granular chromatin, and
indistinct nucleoli.
• Immunohistochemical stains indicating the presence of small
cell carcinoma include:
• Keratin
• Tissue transcription factor-1 (TTF-1)
• Epithelial membrane antigen
• Immunohistochemical markers of neuroendocrine differentiation
include:
• Synaptophysin
• Chromogranin
• Neuron-specific enolase

5. Clinical Presentation
• Present as a large hilar mass and bulky mediastinal lymphadenophathy
cough, dyspnoea
• 70% of SCLCs are metastatic at diagnosis
• Symptoms of metastasis
• SCLC is the most common solid tumor associated with paraneoplastic
syndromes:
• SIADH, ACTH production syndrome, and Eaton–Lambert syndrome.

7. Initial Evaluation
• History and physical examination
• Complete blood picture
• Electrolytes, liver function test, calcium, LDH
• BUN, creatinine
• Chest/liver/adrenal CT with contrast
• Brain MRI or CT with contrast
• PET/CT scan
• Smoking cessation counseling and intervention

8. Staging
Limited stage
• AJCC (7th edition) Stage I-III (T any, N any, M0) that can be safely
treated with definite radiation doses.
• Excludes T3-4 due to multiple lung nodules that are too extensive or
have tumor/nodal volume that is too large to be encompassed in a
tolerable radiation plan.
Extensive stage
• AJCC (7th edition) Stage IV (T any, N any, M 1a/b), or
• T3-4 lung nodules that are too extensive or have tumor/nodal volume
that is too large to be encompassed in a tolerable radiation plan.

9. The American Joint Committee on Cancer
(AJCC) Staging, Seventh edition (2010)

10. Primary tumor (T)
T x Primary tumor cannot be assessed, or tumor proven by the
presence of malignant cells in sputum or bronchial washings,
but not visualized by imaging or bronchoscopy
T3 Tumor > 7 cm
or
one that directly invades any of the following:
 parietal pleural (PL3) chest wall (including superior sulcus
tumors), diaphragm, phrenic nerve, mediastinal pleura, and
parietal pericardium;
 or tumor in the main bronchus (less than 2 cm distal to the
carina*) but without involvement of the carina; or
 associated atelectasis or obstructive pneumonitis of the entire
lung or separate tumor nodule(s) in the same lobe
T 0 No evidence of primary tumor
T is Carcinoma in situ
T 1 Tumor 3 cm or less in greatest dimension, surrounded by lung
or visceral pleura, without bronchoscopic evidence of invasion,
more proximal than the lobar bronchus (i.e., not in the main
bronchus)
T1a:
Tumor ≤2 cm in greatest dimension T4 tumor of any size that invades any of the following:
 mediastinum,
 heart,
 great vessels,
 trachea,
 recurrent laryngeal nerve,
 esophagus,
 vertebral body,
 carina,
 separate tumor nodule(s) in a different ipsilateral lobe
T1b: Tumor > 2 cm but ≤3 cm in greatest dimension
T 2 Tumor > 3 cm but ≤7 cm
Or
tumor with any of the following features (T2 tumors with these
features are classified T2a if 5 cm or less);
 involves main bronchus, 2 cm or more distal to the carina;
 invades visceral pleura (pl1 or pl2);
 associated with atelectasis or obstructive pneumonitis that
extends to the hilar region but does not involve the entire
lung
T2a: Tumor > 3 cm but ≤ 5 cm in greatest dimension
T2b: Tumor >5 cm but ≤ 7 cm in greatest dimension

11. Region lymph nodes (N)]
Nx Regional lymph nodes can’t be assessed
N0 No regional LN metastasis
N1 Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including
involvement by direct extension
N2 Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)
N3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular
lymph node(s)
Distant metastasis (M)
M0 No distant metastasis
M1 Distant metastasis
M1a: Separate tumor nodule(s) in a contralateral lobe tumor with pleural nodules or malignant pleural (or pericardial)
effusion
M1b: Distant metastasis

13. 5 year survival Medain survival
IA 50-70% IA 5-10 yr
IB 40-60% IB 3-7 yr
IIA 55% IIA 3-4 yr
IIB 40% IIB 1.5- 3 yr
IIIA 20-25% IIIA 14-23 months
IIIB 7-9% IIIB 10-16 months
Superior sulcus : 3year 50% IV
6-18 months (best supportive care 3-6
months; 8-10 months with chemo)
Handbook of Evidence-based Radiation Oncology. 2nd Edition. 2010.

14. Prognostic Factors
Adverse prognostic factors include
• Poor performance status (PS) (Eastern Cooperative Oncology Group PS [ECOG
PS] = 3 to 4)
• Weight loss
• High disease burden (high LDH levels)
Favorable prognostic factors in limited stage disease include
• Female gender
• Normal LDH
• Stage I disease
Favorable prognostic factors in metastatic disease include
• One metastatic site
• Normal LDH

15. Initial Evaluation
Staging
Initaial treatment
Response assessment folllowing initial treatment
Complete response, Partial Response, stable disease, Progressive disease
Adjuvant Treatment
Surveillance
Relpase or progressive disease
Subsequent treatment/Pallitive therapy
General Outline of NCCN
Guidelines

16. Clinical Stage T1-1, N0
Pathological mediastinal staging
negaitve
Lobectomy and
mediastinal lymph node
dissection or sampling
N0 Systemic therapy
N1
Concurrent systemic
therapy + mediastinal RT
Pathological mediastinal
staging positive
Or
Medically inoperable
Or decision made not to
persue surgical resection
Limited stage in excess of T1-2, N0
Good PS (0-2) Systemic therapy + Concurrent RT
Poor PS (3-4) due to SCLC
Systemic therapy ± RT (concurrent or
sequential)
Poor PS (3-4) not due to SCLC
Individualized treatment including
supporting care
Limited Stage

17. Extensive stage
Without localized
symptomatic
sites or brain
metastases
Extensive stage
+ localized
symptomatic
sites
Extensive stage
with brain
metastasis

18. Without localized
symptomatic sites
or brain
metastases
- Good PS (0-2)
- Poor PS (3-4)
Due to SCLC
Combination of
systemic therapy
including
supportive care
Poor PS (3-4) not
due to SCLC
Individualized
therapy including
supportive care

19. Extensive stage + localized
symptomatic sites
- SVC syndrome
- Lobar obstruction
- Bone metastases
Systemic therapy ± RT to
symptomatic sites
If high risk of fracture due
to osseous structural
impairment , consider
orthopedic stabilization
and palliative external-
beam RT
Spinal cord compression
RT to systemic sites before
systemic therapy unless
immediate systemic
therapy is required

20. Extensive stage with
brain metastasis
Asymptomatic
May administer systemic
therapy first, with whole-
brain RT after systemic
therapy
Symptomatic
Whole-brain RT before
systemic therapy, unless
immediate systemic
therapy is indicated

21. Response assessment following Initial
Therapy
• Chest x-ray
• Chest/liver/adrenal CT with contrast
• Brain MRI or CT with contrast, if prophylactic cranial irradiation
(PCI) to be given
• Complete blood picture
• Electrolytes, LFTs, Cal

22. Complete response or partial response
Stable Disease
Primary progressive disease

23. Complete response or partial response
Limited stage
PCI
Extensive Stage
PCI ± thoracic RT
After recovery from primary therapy:
- Oncology follow-up visits every 3-4 mth during 1-2 yr, every 6 mth during 3-5 yr, then annually
- New pulmonary nodule should initiate workup for potential new primary
- Smoking cessation intervention
Stable Disease

24. Primary progressive
disease
PS 0-2
Subsequent systemic therapy
Or
Palliative symptom management, including localized RT to symptomatic sites
Response
Continue until two cycles beyond best response or progression or
development of unacceptable toxicity
Progression
No response or
unacceptable toxicity
PS 3-4
Palliative symptom management, including localized RT to
symptomatic sites

25. Principle of Surgical Resection
• Stage I SCLC is diagnosed in less than 5% of patients with
SCLC
• Disease in excess of T1-2, N0 not benefit from surgery
• Prior to resection
• To rule out occult nodal disease

26. Principle of Supportive Care
• Smoking cessation advice, counseling, and pharmacotherapy
• Granulocyte colony-stimulating factor (G-CSF) or granulocyte-
macrophage colony-stimulating factor (GM-CSF) is not
recommended during concurrent systemic therapy plus radiotherapy
(Bunn PA, Crowley J, Kelly K, et al. Chemoraditherapy with or without granulocyte-macrophage colony-
stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized
study of the Southwest Oncology Group. J Clin Oncol 1995;13:1632-1541.)
• Treatment of Syndrome of inappropriate antidiuretic hormone
• Treatment of Cushing’s syndrome
• Pain management
• Nausea/vomiting
• Psychological distress

27. Principle of systemic therapy
Systemic therapy as primary or adjuvant
therapy
Limited stage (maximum of 4-6 cycles)
- Cisplatin and etoposide
- Carboplatin and etoposide
- During systemic therapy + RT, cisplatin/etoposide is
recommended
- Use of myeloid growth factor is not recommende during
concurrent systemic therapy plus radiotherapy
Extensive stage (maximum of 4-6 cycles)
- Carboplatin and etoposide
- Cisplatin and etoposide
- Carboplatin and irinotecan
- Cisplatin and irinotecan

28. Subsequent systemic therapy
• Clinical trial preferred
Relapse > 6 mth
• Original regimen
Relpase ≤ 6 mth
• Topotecan
• Irinotecan
• Paclitaxel
• Docetaxel
• Temozolamide
• nivolumab ± ipilimumab
• Vinorelbine
• Oral etoposide
• Gemcitabine
• Cyclophosphamide/doxorubicin/vincristine (CAV)
• bendamustine

29. Response assessment
• Limited-stage
• Adjuvant therapyAfter completion of initial therapy
• Systemic therapy alone or sequential systemic therapy
followed by RT after every 2 cycles of systemic therapy
and at completion of therapy
• Extensive-stage
• After 2-3 cycles of systemic therapy and at completion of
therapy
• Subsequent systemic therapy
• After 2-3 cycles of systemic therapy and at completion of
therapy

30. Principle of Radiation Therapy
General Principle
• Has a potential role in all stages of SCLC, as part of either
definite or palliative therapy
• To maximize tumor control and to minimize treatment toxicity
• Critical components of modern RT
• Appropriate simulation
• Accurate target definition
• Conformal RT planning
• Ensuring accurate delivery of the planned treatment

31. Limiting Stage
Timing
• RT should start early, with cycle 1 or 2 of systemic therapy
• A shorter time from the start of any therapy to the end of RT is significantly
associated with improved survival
Target definition
• Based on the pretreatment PET scan and CT scan
• Systemic therapy before RT gross tumor volume (GTV) limited to post
induction systemic therapy volume
Doses and schedule
• Optimal schedule of RT have not been established.
• 45Gy in 3 wks (1.5 Gy twice daily) is superior to 45Gy in 5 weeks (1.8 Gy daily)
• Once daily RT  higher doses of 60-70Gy

32. Extensive Stage
Consolidative thoracic RT
• Well tolerated
• Results in fewer systemic chest recurrences and improves long
term survival

33. Prophylactic Cranial Irradiation(PCI)
• In patients with limited stage disease who have a good
response to initial therapy, prophylactic cranial radiotherapy
(PCI) reduces the incidence of brain metastases and increases
overall survival
• In patients with extensive stage disease reduces the incidence
of brain metastases
• Dose – 25 Gy in 10 daily fractions
• Shorter course of extensive disease e.g., 20 Gy in 5 fractions
• Not recommended in patients with poor performance status or
impaired neurocognitive functioning

34. Brain metastasis
• Whole brain radiation therapy rather than stereotatic
radiotherapy
• Recommended dose for WBRT – 30 Gy in 10 fractoins

35. Lung Neuroendocrine Tumors
Low-grade neuroendocrine carcinoma(typical carcinoid)
Intermediate-grade neuroendocrine carcinoma (atypical
carcinoid)
High-grade neuroendocrine carcinoma (large-cell
neuroendocrine carcinoma)
High-grade neuroendocrine carcinoma (small cell carcinoma)
Combined SCLC and NSCLC

36. High-grade neuroendocrine carcinoma (large-cell
neuroendocrine carcinoma)
• NCCN Guidelines for NSCLC
High-grade neuroendocrine carcinoma (small cell carcinoma)
Combined SCLC and NSCLC
• NCCN Guidelines for SCLC

37. Low-grade neuroendocrine carcinoma(typical carcinoid)
Stage I-II
Surgery: lobectomy or
other anatomic resection
+ mediastinal lymph node
dissection or sampling
Stage IIIA
Surgical candidate
Non surgical candidate
Cisplatin/etoposide
+ RT
Stage IIIB (except
T4 due to multiple
lung nodules)
Cisplatin/etoposide +
RT
Stage IIIB (T4
due to multiple
lung nodules)or
stage IV
Consider observation for
asymptomatic, low-bulk
disease or systemic
therapy
Follow-up every 6-12 mths post treatment up to 10 yrs
- H&P
- Chest CT annually
Biochemial evaluation

38. Intermediate-grade neuroendocrine carcinoma(Atypical carcinoid)
Stage IIIA
Surgical candidate
Non surgical
candidate
Cisplatin/etoposide
+ RT
Stage IIIB (except
T4 due to multiple
lung nodules)
Cisplatin/etoposide +
RT
Stage IIIB (T4
due to multiple
lung nodules)or
stage IV
systemic therapy
Stage I-II
Surgery: lobectomy or other
anatomic resection + mediastinal
lymph node dissection or sampling
Stage I
observe
Stage II, III
Cisplatin/etoposide ± RT
Follow-up every 6-12 mths post treatment up to 10 yrs
- H&P
- Chest CT annually
Biochemial evaluation

39. Principle of Systemic Therapy
High-Grade NET (Atypical Carcinoid
• Cisplatin/etoposide (preferred)
• Capecitabine + temozoalmide
• Temozolamide
• Sunitinib
• Everolimus
• Consider octreotide or lanretide, if octreoride
scan positive or symptoms of carcinoid
syndrome
Low-Grade NET (Typical Carcinoid
• Capecitabine + temozoalmide
• Everolimus
• Cisplatin/etoposide
• Temozolamide
• Sunitinib
• Consider octreotide or lanretide, if
octreoride scan positive or symptoms of
carcinoid syndrome

40. THANK YOU