Small cell lung carcinoma from anatomy to management including NCCN data and Trials

1. SCLC -ANATOMY TO
MANAGEMENT
Dr. Brijesh Maheshwari
Moderator-Dr.Pavan Kumar/Dr.
Rashika Sachan /Dr. Srinivas sir/
Dr. Prachi Upadhyaya

2.  Epidemiology & Risk Factors
 Clinical Presentation
 Histology
 Diagnostic workup
 Staging
 Surgery
 Radiotherapy with evidence
 NCCN flow chart for management
 Adverse factors
 Take home message

3. EPIDEMIOLOGY
 In the world, lung cancer accounts for 11.6% of total cases and 18% cancer related deaths.
 Of the 42000 patients in the UK and 225000 in the USA diagnosed with lung cancer every year,
15% have small-cell lung cancer and 30% of those have limited-stage disease(Lancet Oncol 2021; 18:
1116–25 Published Online June 19, 2021)
 Lung cancer is rare below age 40, with rates increasing until age 80, after which the rate tapers
off.
 Approximately two thirds of patients with SCLC have extensive stage or stage IV disease at
presentation

5. • In India, lung cancer constitutes 5.9 per cent of all new cancer cases and
8.1 per cent of all cancer related deaths in both sexes.
• Highest reported incidence: Mizoram; in both males and females.
• The time trends of lung cancer shows a significant rise in Delhi, Chennai
and Bengaluru in both sexes.
• The incidence and pattern of lung cancer differ as per geographic region
and ethnicity and largely reflect the prevalence and pattern of smoking.
Indian Scenario

6. RISK FACTORS
Majority (80–90%) by cigarette smoking.
-Cigarette smokers have a 10 fold or greater increase in risk.
-One genetic mutation is induced for every 15 cigarettes smoked.
- Cigarette smoking increases the risk of all the major lung cancer cell types.
- Environmental tobacco smoke (ETS) or second hand smoke is also an
established cause of lung cancer.
Radon exposure is now the 2nd cause of Lung cancer in USA

7. • Genetic predisposition
• Genetic trait : Li Fraumeni syndrome (P53 mutation)
• Gene polymorphisms:
• DNA repair genes : XRCC1
• COX 2
• Interleukin 6
• Dietary influence
• Folate & B12 deficiency
• Inadequate antioxidant consumption

8. • Occupational & Environmental exposure
• Asbestos exposure: Occupational or residential (silicate type fibers)
• Foundry workers and welders: Ni, Co, Cd
• Uranium mine workers: Inhaled Radon
• Air pollution:
• Diesel exhaust
• Metal fumes
• Air sulfate and PAH content

9. • Over 40 carcinogens have been identified in cigarette smoke.
• Examples include:
 Particulate phase carcinogens: Benzo-pyerene, Nicotine, Tobacco specific
nitrosamines, Nickel, Cadmium;
Gaseous phase carcinogens: Hydrazine and Vinyl Chloride.
• Carcinogens act by:
Mutating certain dormant Oncogenes (as Ras oncogene)  activating
them;
Mutating certain active Tumor suppressor genes ( as P53)  inhibiting
them.

10. HISTOLOGY
• SCLC is one of the small, round, blue cell tumors

11. Genes Somatically Altered in Different Histologic
Subtypes of Lung Cancer
Histology Oncogene Tumor-Suppressor genes
Adenocarcinoma EGFR
KRAS
ALK
TP53
CDKN2A/B(p16, p14)
LKB1
Squamous cell carcinoma EGFR
PIK3CA
IGF-1R
TP53
TP63
Small cell carcinoma MYC
BCL-2
TP53
RB1
FHIT
Large cell carcinoma not well studied not well studied
:Harrison's Principles of Internal Medicine, 18e

12. D/D of Round Blue Cell Tumor
1.carcinoid tumor 10.Neuroblastoma
2.Mesothelioma 11.Desmoplastic round cell
tumour
3.Medulloblastoma 12.Hepatoblastoma
4.merkel cell ca 13.Chromophobe RCC
5. mesenchymal chondrosarcoma 14.Retinoblastoma
6.synovial sarcoma 15.Rhabdomyosarcoma
7.Small cell lung cancer 16. Leiomyosarcoma
8.Small cell lymphoma 17. Wilms tumor
9.Ewing sarcoma/pnet

13. Clinical Features: Thoracic Disease
Local Symptoms Cough
Dyspnea
Chest Pain
Mediastinal Involvement Hoarseness
Retrosternal Chest pain
Vocal Cord Palsy
Horner's Syndrome
Superior Vena Caval Syndrome
Hemoptysis
Post obstructive Wheezing

14. Clinical Features: Extrathoracic
• Brain Metastasis:
• Approximately 50% of SCLC patients
develop brain metastases during the
course of their disease.
• Presentation varies:
• Discreet ICSOL(s)
• Leptomeningeal infiltration
• Unlike other metastasis Brain mets are
symptomatic in 90% at presentation

15. SUPERIOR VENA CAVA SYNDROME
• Results from obstruction of blood flow to the heart from the head and neck
regions and upper extremities.
• It occurs as a consequence of compression of the superior vena cava, either
from direct invasion by the primary tumor into the mediastinum or from
lymphatic spread with enlarged right paratracheal lymph nodes.
• It is commonly caused by SCLC but can result from any centrally located
tumor or mediastinal spread.

16. Features
1. Feeling of fullness in the head
2. Dyspnea
3. Cough
4. Dilated neck veins
5. Prominent venous pattern on the face and the chest
6. Upper extremity and facial edema
7. Papilledema
8. Facial cyanosis
9. Plethora
10. Conjunctival edema(possibly)

17. PARANEOPLASTIC SYNDROMES
 SIADH – Small cell carcinoma –
 It results into Hyponatremia
 Symptoms include-Headache, Muscle cramps, Anorexia & Decreased urine output
 Resolves within 1–4 weeks of initiating chemotherapy.
 Demeclocycline is the agent of choice.
 Cushing Syndrome-ACTH-producing tumors – Small cell-
 Symptoms-Muscle weakness, weight loss, hypertension, hirsutism & osteoporosis.
 Hypokalemic alkalosis and hyperglycemia are present.
 It has worse prognosis.

18.  Hypercalcemia -
 It is associated with secretion of:
 parathyroid hormone-related protein(PTHrp),
 calcitriol or
 other cytokines including osteoclast activating factors
 Clinical symptoms include
 Anorexia,
 Nausea, Vomiting,
 Abdominal Pain,
 Lethargy,
 Constipation,
 Polyuria and Polydipsia.
 Late symptoms- Renal failure, confusion and coma.

19.  Lambert-Eaton Myasthenic Syndrome(LEMS)
 It is characterized by muscle weakness of the limbs.
 Proximal muscles are affected; associated with difficulty in climbing chairs
and rising from a sitting position.
 Chemotherapy is the initial treatment of choice.
• Skeletal–
 Clubbing - 30% (usually NSCLCs)
 Hypertrophic primary osteoarthropathy - 1–10% (usually
adenocarcinomas).
 Periostitis

20. • Neurologic –
 Myopathic syndromes - 1%
 Myasthenic Eaton-Lambert syndrome and retinal blindness (SCLC).
 Peripheral neuropathies,
 Subacute cerebellar degeneration,
 Cortical degeneration, and
 Polymyositis
• Hematologic manifestations – 1-8%
 -Migratory venous thrombophlebitis (Trousseau's syndrome),
 -Nonbacterial Thrombotic (marantic) endocarditis with arterial emboli,
 -Disseminated intravascular coagulation
 -Thrombotic disease complicating cancer is usually a poor prognostic
sign.

21. Lung Cancer Mets
• Adrenals-50% of cancer
• Liver-30-50 %
• Brain-20%
• Bone-20%

22. DIAGNOSTIC WORK UP
• Complete history
• Complete physical examination
Chest-may show signs of-
I. Partial or complete obstruction of airways
II. Pneumonia
III. Pleural Effusion
Neck Examination- Signs of Supraclavicular lymphadenopathy
Abdominal examination- sign of hepatomegaly
Neurological examination- signs of Brain metastasis

23. BLOOD INVESTIGATIONS
• CBC- anemia due to metastatic disease
• LFT- May indicate Liver mets
• Increased ALP- May indicate Liver or Bone mets
• Increased Calcium ion levels -May indicate Bone mets or Paraneoplastic
syndrome

24. RADIOLOGIC EXAMINATION
• Chest Xray-initial imaging modality.
A tumor visible in chest X ray has usually completed 75% of it’s natural
history.
Current Xray should be compared with previous ones to determine if
lesion is-
New
Enlarging or
Stable

25. Chest X rays
Pleural Effusion
Phrenic Nerve
palsy
Mass
Collapse

26. • CT Scan-
CECT Chest + Upper Abdomen should be done so that Liver and Adrenals can be
visualized
In a patient with known lung cancer a lymph node is considered suspicious if it
measures >1cm in diameter on its short axis.
MRI Brain
All patients with SCLC, regardless of stage, should undergo brain MRI with
gandolinium or head CT with contrast to evaluate brain metastasis.

27. • PET or PET-CT SCAN
• It has become standard in the staging work up of lung cancer patients.
• The biggest advantage is the identification of suspicious lymph nodes or
distant metastasis.
• Kaeff et al (2001) prospectively evaluated the utility of PET-
They found that PET correctly upstaged 26% patients
and downstaged 10% patients.
• Additionally PET can detect malignant disease in lymph nodes of normal size.
• PET-CT is superior to CT or PET alone and can detect malignancies in
tumors as small as 0.5cm.

28. • Percutaneous Fine Needle Aspiration(FNA)-
 CT guided FNA done in lesions which cannot be reached by Bronchoscopy.
Overall diagnostic yield is 80%.
• Bronchoscopy-
• FOB is done and cytologic brushings, biopsies can be taken.

30. SPUTUM CYTOLOGY AND LUNG CANCER
• While this procedure has not been found to be
an effective screening test for lung cancer
when done on someone with symptoms, it can
sometimes result in a diagnosis of lung
cancer.
• Sputum Cytology-Sensitivity is 65%.

31. CT guided biopsy

32. • Endoscopic FNA-
• Endobronchial USG guided transbronchial needle aspiration(EBUS-TBNA) can be done for
ultrasound suspicious lymph nodes-
Paratracheal- Level 2 & 4
Subcarinal- Level 7
Hilar lymph node stations- Level 10

33. Thoracocentesis-
If on multiple taps; pleural fluid is consistently bloody or exudative ,it should
be considered malignant.

34. MEDIASTINOSCOPY AND MEDIASTINOTOMY
Chamberlain procedure or video-assisted thoracoscopic techniques

35. • Thoracoscopy
• Video assisted thoracoscopy
(VAT) is used for-
I. Diagnosis
II. Staging
III. Resection of lung cancer
• Peripheral nodules can be easily
seen and excised.
• It can also be used to reach
mediastinal nodes not accessible
by standard mediastinoscopy,
EBUS-TBNA or EUS-FNA
techniques.

36. Staging
• The VALSG (Veterans' Administration Lung Study Group) is the most commonly used
system
• Revised by Zelen M in 1973
• Depends on the ABILITY to safely encompass the entire tumor in a single Radiation
portal.

37. VALSG Definition
Limited disease patients are characterized by
• Disease confined to one hemithorax, although local extensions may be present;
• No extrathoracic metastases except for possible ipsilateral, supraclavicular nodes if
they can be included in the same portal as the primary tumor; and
• Primary tumor and regional nodes which can be adequately treated and totally
encompassed in portal.
Extensive disease patients a who cannot be classified as having limited disease, or
with malignant pleural effusion.

39. Tumor ≤ 3 cm in greatest dimension, surrounded by
lung or visceral pleura, without bronchoscopic
evidence o f invasion more proximal than the lobar
bronchus (i.e., not in the main bronchus)
T1mi- Minimally invasive adenocarcinoma: adenocarcinoma
(≤ 3 cm in greatest dimension) with a predominantly lepidic
pattern and ≤ 5 mm invasion in greatest dimension.
T1a- Tumor ≤ 1 cm in greatest dimension. A superficial,
spreading tumor o f any size whose invasive component is
limited to the bronchial wall and may extend proximal to the
main bronchus also is classified as T1a , but these tumors are
uncommon.
T1b- Tumor >1 cm but ≤ 2 cm in greatest dimension
T1c- Tumor >2 cm but ≤ 3 cm in greatest dimension

40. Tumor >3 cm but ≤ 5 cm or having any of the following features:
Involves the main bronchus regardless of distance to the carina, but without involvement of the carina
Invades visceral pleura (PL1 or PL2)
Associated with atelectasis or obstructive pneumonitis that extends to the hilar region, involving part or all of the lung
T2 tumors with these features are classified as T2a if ≤ 4 cm or if the size cannot be determined and T2b if >4 cm but ≤ 5
cm.

41. Tumor >5 cm but ≤ 7 cm in greatest dimension or
directly invading any of the following:
Parietal Pleura (PL3),
Chest Wall (Including Superior Sulcus Tumors),
Phrenic Nerve,
Parietal pericardium; or
Separate tumor nodule(s) in the same lobe as the
primary

42. Tumor >7 cm or tumor of any size invading one or more of
the following:
1. Diaphragm,
2. Mediastinum,
3. Heart,
4. Great Vessels,
5. Trachea,
6. Recurrent Laryngeal Nerve,
7. Esophagus,
8. Vertebral Body, Or
9. Carina;
10. Separate tumor nodule(s) in an ipsilateral lobe
different from that of the primary

43. • N0:
• No regional LN metastases
• N1:
• LN mets in ipsilateral peribronchial and/or
ipsilateral hilar and intrapulmonary nodes (Levels
10, 11, 12, 13, 14)
• N2:
• Ipsilateral mediastinal and/or subcarinal lymph
nodes
• N3:
• Contralateral mediastinal /hilar
• Ipsilateral or contralateral supraclavicular/ scalene
nodes

46. Stage IV A
Stage IV B

47. MANAGEMENT
RADIOTHERAPY
SURGERY CHEMOTHERAPY

48. TYPES

49. Radiotherapy Volumes
• Conformal RT is the current standard RT technique for both definitive and
postoperative radiotherapy.
• If conformal therapy facilities are available, conventional RT is not
recommended due to its high toxicity and inability to escalate total
radiation dose.
• Only the primary tumor and involved lymphatic regions are irradiated in
conformal therapy.

50. Dose and Fractionation
• SCLC is highly radiosensitive, suggesting that hyperfractionation could
be employed to reduce late normal tissue toxicity.
• It also has a high proliferative rate, arguing for accelerated treatment
to counteract repopulation.

52. Prophylactic Cranial Irradiation
• Brain metastases are present at diagnosis in approximately 20% of
patients with SCLC.
• The brain is also a frequent site of failure after chemotherapy for extensive
disease or chemoradiotherapy for limited-stage disease.
• Several randomized trials have addressed the value of PCI following a
response to initial therapy and have consistently demonstrated a decrease
in the incidence of brain metastases.

53. • 25 Gy in 10 fractions as the current preferred
regimen to deliver PCI.

60. SBRT
• High-dose focused radiation may provide high probability of local tumor
control when surgical approaches are not indicated – Medical inoperability
• Improved therapeutic ratio over fractionated RT courses
• High dose focused radiation promises similar tumor control where limited
surgical approaches are standard of care.

62. SBRT-Target volume considerations
• SBRT target volume definition in the absence of 4DCT Imaging
- Free breathing scan
• GTV is visible tumor
• PTV is GTV + 5 mm axial/10 mm cranio-caudal
• With 4DCT maximum intensity projection (MIP) used for planning

69. Adverse Prognostic Factors
• Age > 65
• Performance status > 2
• Advanced stage
• Presence of mediastinal lymphadenopathy
• Tumor hypercalcemia
• Surgical procedure : Limited resection
• Positive resection margins
• Biological markers:
• COX 2
• p 53
• EGFR
• erbB2

70. Take Home Message
• Accounts for 13% of all lung cancers.
• Tobacco consumption is the most common cause.
• It is a type of round blue cell tumor.
• SIADH is the most common Paraneoplastic Syndrome.
• Patients treated concurrently has longer median survival as compared to
patients treated sequentially.
• 45 Gy in 30 fractions twice daily is better than 66 Gy in 33 fractions once
daily.
• Intracranial metastasis occur in more than 50% of patients.

71. • PCI is a Category I recommendation for patients with limited
stage disease who attain a complete or partial response.
• PCI should not be given concurrently with systemic therapy or
high dose radiation therapy.
• Optimal dose of PCI is 25Gy in 10#.
• Cisplatin + Etoposide is the most commonly used
chemotherapy regimen.

73. THANK YOU