1. Small cell lung carcinoma is a highly aggressive malignancy associated with tobacco exposure. It is characterized pathologically by small, round, blue cells with scant cytoplasm and fine chromatin. 2. Prognostic factors include stage, performance status, gender, and normal LDH levels. Staging workup involves imaging of the chest, abdomen, brain and bone as well as biopsy of suspicious lesions. 3. Treatment depends on stage - limited stage receives chemotherapy with thoracic radiation while extensive stage receives chemotherapy alone with consideration of prophylactic cranial irradiation for those who respond to initial treatment. The standard chemotherapy regimen is etoposide and platinum.

1. SMALL CELL CARCINOMA LUNG
Kanmani Velarasan
CMC Vellore

2. INTRODUCTION
 Highly aggressive malignant epithelial tumor
• Tobacco exposure - >95% cases
• Screening – not recommended

3. PATHOLOGY(WHO 1999)
• Small round blue cell tumor with scant
cytoplasm, fine granular nuclear chromatin
and indistinct nucleoli.
• Immnoreactive to Keratin, EMA and
TTF1(80%).
• Majority stain for Synaptophysin,
chromogrannin A, NSE and CD56

4. PROGNOSTIC FACTORS
• Stage
• Performance status
• Female gender
• Normal baseline LDH value

6. STAGING WORKUP
• History, physical examination, lab and
radiological evaluation.
• Clinical examination – Special attention to
paraneoplastic syndromes.
• All patients regardless of stage – Image brain.
• CT of chest & abdomen and bone scan
• Staging should not delay onset of treatment
more than 1 week

7. • PET-CT - 9% patients are up- and 4%
downstaged.
• PET-CT findings which could impact treatment
decisions should be pathologically confirmed.
• In case of abnormal blood count or signs of
blood–bone marrow barrier rupture (e.g.
peripheral blood erythroblasts), a BM
aspiration and biopsy indicated

8. • Solitary metastasis – Pathological confirmation
should not delay treatment start.
• Solitary metastatic lesion’s size should be re-
evaluated after two cycles.
• Alternatively, an initial second radiological
method is recommended.
• If a pleural or pericardial effusion is the only site
of M1, no malignant cells are identified in the
pleural fluid, treatment should be according to an
M0 status

9. Pleural effusion
• If effusion is too small or
1. 3 cytopathologic examination are negative
2. Fluid is not bloody or not exudate
3. Clinical judgement – that effusion not related
to cancer

11. STAGE (VALSG system)
LIMITED STAGE DISEASE
• Disease confined to
ipsilateral hemithorax,
which can be safely
encompassed within a
tolerable radiation field.
EXTENSIVE STAGE DISEASE
• Disease beyond ipsilateral
hemithorax which may
include malignant pleural
or pericardial effusion or
hematogenous metastasis

15. Management of localised disease
(T1-4, N0-3 M0)
• Median survival - 15–20 months
• 2-year survival rates - 20%–40%
• 5 year survival - 20%–25%
• 5% of patients with SCLC present as T1, 2 N0,1
M0 tumours (5-year survival rates in the
order of 50%)

16. • Surgical approach in this group of patients is
justified after ruling out mediastinal lymph node
involvement (CT scan, PET-CT scan or EBUS
and/or mediastinoscopy if enlarged) .
• Postoperatively, four cycles of adjuvant
chemotherapy should be administered.
• In case of unforeseen N2 or N1 or who have not
undergone systematic nodal dissection,
postoperative radiotherapy should be considered.
• There is no role for surgery after induction
chemotherapy in N2 disease

17. • General condition of the patient - concurrent
treatment or lung constraints -- chest
irradiation may be postponed until the start of
the third cycle of chemotherapy

18. Management of metastatic disease
• Outcomes remain poor with a median
progression-free survival (PFS) of only 5.5 months
and a median OS of <10 months
• 4–6 cycles of etoposide plus cisplatin or
carboplatin are recommended
• Patients in a reasonably good PS with any
response to first-line treatment should be
evaluated for PCI

20. THORACIC RADIATION THERAPY
FOR SMALL CELL LUNG CANCER
EVIDENCE

21. • Pignon et al – Chemoradiotherapy arm vs
chemotherapy alone arm – 5.4% difference in
3 year survival. Local failure – 52% vs 77%
• 25-30% reduction in local failures and 5-7%
improvement in 2 year survival

22. ROLE OF CHEMORT IN LOCALISED
DISEASE
• JCOG Trial – Concurrent Vs Sequential
chemotherapy and radiation
Concurrent CRT – Longer median
survival(27 months Vs 20 months)
• NCIC – Early Vs Late concurrent CRT
Early CRT – Improved median survival(21 Vs 16
months)

23. TIMING
• Fried et al – Early thoracic RT with cycle 1 or 2-
Improved 2yr OS – benefit more pronounced
with platinum based chemotherapy.
• Pijls et al – higher survival rates when thoracic
RT started within 30 days of initiation of
chemotherapy

24. DOSE & FRACTIONATION
• Highly radiosensitive – Hence role of hyper
fractionation.
• Inter group trial 0096 (Turrisi et al) – Once
daily RT Vs Twice daily RT
1. In twice daily arm - OS significantly higher(26
% Vs 16 % at 5 yr), Lower local recurrence
rate(36% Vs 52%)
2. Increased grade3 Esophagitis(26 % Vs 11%)
3. No difference in late toxicity.

25. • Optimal dose and fractionation remains to be
defined.
• Dose escalation trial – RTOG 0239(50.4 Gy to
64.8 Gy).
• CALGB 39808 – Tested 70 Gy in 35 fractions.
• CONVERT TRIAL – 45 Gy in 30 fractions BD Vs
66 Gy in 33 fractions in OD

26. RADIOTHERAPY VOLUME
• SWOG TRIAL – Pre induction Vs Post induction
volume.
No difference in local recurrence rate (32% Vs
28%)
No elective nodal irradiation as most
intrathoracic failures occur in post chemoRT
field.

27. FIELD
• 1.5 cm of margin between GTV and PTV
• Dose to Spinal cord limited to 41 Gy in the
twice daily arm.

28. DOSE CONSTRAINTS (RTOG 0538
PROTOCOL)
• Spinal cord – <41 Gy(BD arm) and <50.5Gy
(OD arm)
• Lungs – V20 <40%, MLD - <20 Gy
• Esophagus - < 34 Gy
• Heart – 60 Gy < 1/3, 45 Gy <2/3 and 40 Gy <
100% of heart

29. THORACIC RT FOR METASTATIC
DISEASE
• Systemic therapy – Essential element.
• Jeremic et al – Patient with partial response
1. ChemoRT Vs Further chemotherapy.
2. Higher OS in the ChemoRT arm (9% Vs 5% at
5 yrs)
• RTOG 0937 and CREST trial – Role of thoracic
RT studied

30. PROPHYLACTIC CRANIAL RT
• Brain metastasis at diagnosis - 10-14 % (Seute
et al)
• Meta-analysis – PCI Vs Observation
PCI decreased the incidence of brain
metastasis(59 % Vs 33 % at 3 yrs) and improved
OS(21 % Vs 15 %).

31. • Preferred regimen : 25 Gy in 10 fractions (less
neurologic toxicity)
• EORTC trial – PCI found to be beneficial in
extensive stage (Incidence decreased 15% Vs
40% and 1 yr OS 27% Vs 13 %)

32. CHEMOTHERAPY
• EP regimen – standard of care
• Carboplatin can be substitute for cisplatin
(Skarlos et al , Ann oncol 1994)
• Role of maintenance chemotherapy – Not
beneficial
• Chemotherapy intensification – not beneficial
in extensive stage and also have greater
toxicity

33. PARANEOPLASTIC SYNDROMES
• Neurological
• ACTH ( Cushing’s syndrome )
• Vasopressin ( SIADH )
POORER SURVIVAL (esp Cushing’s syndrome)

34. PARANEOPLASTIC SYNDROMES
• Cushing’s syndrome – 3-7% patients ,
secondary to ACTH production
• Present with hypertension, edema ,
hyperkalemia and weakness.
• At high risk of opportunistic infections
• Advisable to treat with Metyrapone or
ketaconazole prior to chemotherapy

35. • SIADH : secondary to vasopressin production
• Presents with hyponatremia
• Fluid restriction, saline infusion and
demeclocycline
• Endocrine syndromes parallel cancer control

36. • Neurologic syndromes – Autoimmune in origin
• Lambort eaten myasthenic syndrome –
Autoantibodies against presynaptic motor
terminal(Calcium channels)
• Presents with proximal leg weakness
• Encephalomyelitis, cerebellar degeneration
(anti Hu antibodies ANNA -1) and stiff man
syndrome (anti amphiphysin antibodies)

37. • Neurologic syndromes – reported to have
better survival
• Frequently experience progressive neurologic
decline

38. ROLE OF TARGETED AGENTS
• Angiogenesis : Elevated VEGF – poorer
outcomes. Bevacizumab was tried . High rates
of tracheo oesophageal fistula.
• Thalidomide – No significant difference . More
thrombotic events
• Vandetanib – oral small molecule TKI. No
difference in PFS or OS
• Sorafenib – Low response rates

39. • c – Kit : Transmembrane receptor. Imatinib
showed no activity
• Apoptosis : cell line studies showed inhibition
of bcl2 may increase efficacy
• Oblimersen , a bcl 2 antisense oligoucleotide,
addition found to have no benefit

40. • MMP’s inhibitor: MMP overexpression
facilitates metastasis . Marimastat – no
improvement in survival.
• EGFR mutation – rare
• Insulin growth factor receptor 1 – Important
role in growth, division and apoptosis.
Promising area of research.

41. SALVAGE THERAPY
• Relapse or progress less than three months –
response to next line < 10%
• > 3 months – Expected response upto 25%.
• Agents in phase 2 trial – Docetaxel,
Etoposide(oral), gemcitabine, paclitaxel,
toptecan and vinorelbine
• Single agent Topotecan – US FDA approved
(O Brien et al JCO 2006) – 2.3 mg /m2 D1-D5
Q21 days

42. FOLLOW UP

43. A QUICK GLANCE

49. REFERENCES
• PEREZ
• DEVITA
• NCCN
• MDACC
• ESMO GUIDELINES