Lung Cancer

Dr. Suneet Khurana

Lung Cancer

Etiology of Lung Cancer

Tobacco Smoking x 13.3

times (10 – 20) (78-90%)

2nd hand smoke (15%)

Asbestos x 5 – 90 times

Radon (2-3%)

Arsenic

Ionizing radiation

Beryllium, Nickel, Copper

Chromium, Cadmium

Diesel Exhaust

Polycyclic aromatic

hydrocarbons

Epidemiology of Lung Cancer

Epidemiology

Epidemiology

Symptoms - Signs of Lung Cancer

Symptom / Signs

Cough 74%

Dyspnea 37%

Hemoptysis 57%

Recurrent Pneumonia

Chest Pain, Wheezing 25%

Dysphagia

Laryngeal Nerve Paralysis 18%

Horners Syndrome

Pancoast Syndrome

Superior Vena Cava Syndrome

Atelectasis

Pleural Effusion

Pathological Classification

Non Small Cell Lung Cancer

(NSCLC)

Small Cell Lung Cancer

(SCLC)

Squamous Cell Carcinoma 25 – 30% Oat Cell Carcinoma

Adenocarcinoma 35-40% Intermediate Cell Carcinoma

Large Cell Carcinoma 10-15% Combined Cell Carcinoma

TNM Staging (AJC CS ERR)

Primary Tumor -T

T1 Tumor <3cm without invasion more proximal than lobar bronchus

T2 Tumor >3cm OR

of any size with any of the following

- Invades Visceral Pelura

- Atelectasis of less than entire lung

- Proximal extent of at least 2cm from carina

T3 Tumor of any size with any of the following

- Invasion of Chest Wall

- Invasion of Diaphragm, Mediastinal Pleura, Pericardium

- Atelectasis involving entire lung

- Proximal extent within 2cm of carina

T4 Tumor of any size with any of the following

- Invasion of mediastinum

- Invasion of heart or great vessels

- Invasion of vertebral body

- Presence of malignant pleural or pericardial effusion

- Satellite tumor nodes within same lobe as primary tumor

TNM Staging

Nodal Involvement - N

N0 No regional node involvement

N1 Involvement of ipsilateral hilar or ipsilateral peribronchial nodes

N2 Involvement of ipsilateral mediastinal or subcarinal nodes

N3 Involvement of contralateral mediastinal or hilar nodes OR

Ipsilateral or contralteral scalene or supraclavicular nodes

Metastasis - M

M0 Distant Metastasis absent

M1 Distant Metastasis present

Stage I

Stage IA T1 N0 M0

Stage IB T2 N0 M0

Stage II

Stage IIA T1 N1 M0

Stage IIB T2 N1 M0, T3 N0 M0

Stage IIIa

Stage IIIA T3 N1 M0, T1-3 N2 M0

Stage IIIb

Stage IIIB Any T N3 M0, T4 Any N M0

Stage IV

Stage IV Any T Any N M1

Investigations for Lung Cancer

Investigations

Diagnostic Tests Staging Tests

Chest X-Ray CT Scan - Chest, Brain, Abdomen

Bronchoscopy PET Scan

Ultrasound Guided Biopsy Bone Scintigraphy

CT guided Biopsy Mediastinoscopy

Bone Marrow Biopsy

Chest X-Ray – Diagnostic

Fiberoptic Bronchoscopy - Diagnostic

Bronchoscopy Video

Ultrasound Guided Biopsy - Diagnostic

CT Guided Biopsy - Diagnostic

CT Scan - STAGING

PET Scan for STAGING

Fused PET and CT Scan

Mediastinoscopy for STAGING

Bone Scintigraphy for STAGING

Bone Marrow Aspiration - STAGING

Current Treatments for NSCLC

Treatment Options

SURGERY

RADIOTHERAPY

CHEMOTHERAPY

TARGETED THERAPY

Treatment by Stages of Cancer

Stage Description Treatment Options

Stage Ia – Ib Tumor localized in lung Surgical resection

Stage IIa – IIb Tumor spread to local lymph nodes Surgical resection

Stage IIIa Tumor spread to regional lymph

nodes in trachea, chest above

diaphragm

Chemotherapy followed

by radiation or surgery

Stage IIIb Tumor spread to contra lateral

lymph nodes

Combination of

Chemotherapy and

Radiation

Stage IV Tumor metastasis to organs outside

chest

Chemotherapy and or

palliative care

Surgery – Wedge, Lobectomy, Pneumonectomy

Radiation Therapy Treatment of stage I and stage II

NSCLC, radiation therapy alone is considered when surgical resection is not possible.

Role of radiation therapy as surgical adjuvant therapy after resection of the primary tumor is controversial.

Radiation therapy reduces local failuresin completely resected (stages II and IIIA) NSCLC but has not been shown to improve overall survival rates.

Radiation therapy alone used as local therapy has been associated with 5-year survival rates of 12-16% in early-stage NSCLC (ie, T1 and T2 disease).

No randomized trials have directly compared radiation therapy alone with surgery in the management of early-stage NSCLC

Chemotherapy

Only 30% of patients with NSCLC become eligible for surgical resection

50% of patients who undergo resection experience either a local or systemic relapse of cancer

80% of patients with NSCLC end up taking some sort of chemotherapy

Combination chemotherapy has better survival rates than single agent chemotherapy, which has potentially no role in curative therapy of NSCLC.

Adjuvant chemotherapy (after surgery) has failed to elicit any benefits, however neoadjuvant chemotherapy (given prior to surgery) has improved survival in patients with Stage IIIa disease.

Chemotherapeutic AgentsDrug Mechanism of Action Toxicity

Cisplatin / Carboplatin Causes intrastrand and interstrand cross-

linking of DNA, - strand breakage

Tinnitus, Hearing Loss,

Toxic Neuropathy,

Myelotoxic

Vinorelbine It inhibits tubulin polymerization during G2

phase of cell division

Granulocytopenia,

Constipation, Fatigue

Gemcitabine Antimetabolite that acts as inhibitor of DNA

synthesis

Myelosuppression, Flu

like symptoms,

Hemolytic Uremic

Syndrome, Lung

toxicity

Paclitaxel Inhibits tubulin depolymerization in spindle

during cell division

Myelosuppression,

neuropathy,

hypersensitivity

Pemetrexed disodium Disrupts folate-dependent metabolic

processes essential for cell replication.

Fatigue,

myelosuppression,

Infection, GI toxicity

Docetaxel Inhibits cancer cell growth by promoting

assembly and blocking disassembly of

microtubules

Myelosuppression, fluid

retention, HSN rxns

Etoposide Causes single strand breaks in DNA, inhibits

repair of DNA

Myelosuppression,

Transient Hypotension

Targeted Therapy

What are “targeted therapies”?

Cytotoxic vs. Cytostatic

Primarily target malignant cells

Target molecules involved in:

◦ cell growth signal transduction

◦ angiogenesis

◦ metastasis

Generally less toxic at therapeutic doses

Many are oral agents

Targeted Therapies

Targets the HER2 receptor that is

over-expressed in 25% of breast cancers

Targeted Therapies

Targets the VEGF and inhibits angiogenesis in NSCLC and colorectal cancer

Epidermal Growth Factor Receptor EGFR

EGFR is over-expressed in:

• many tumour types

including NSCLC

Tyrosine Kinase Inhibitor