common diseases of the lung and pleural cavity · ginsberg rj, et al. cancer: principles and...

Lung cancer

ร.ศ.น.พ. ธีรวิทย ์ พนัธ์ุชยัเพชร ภาควิชาศลัยศาสตร์ คณะแพทยศาสตร์ศิริราชพยาบาล

International variation in

age-standardized lung cancer

incidence rates per 100,000

population in 2002

new case=1.35 m

dead = 1.18 m

5 year relative survival

M<14%, F<18%

Youlden et al. (J Thorac Oncol. 2008;3: 819–831)

M

F

5.5

6.4

6.7

10

10.8

15

19.1

21.2

21.5

34.9

0 10 20 30 40

Larynx

Oral cavity

Lymphoma

Bladder

Esophagus

Liver

Colorectal

Prostate

Stomach

Lung

Incidence rates (per 100,000)

World Age-adjusted Incidence Rates for Most Common Sites in Men

World Age-adjusted Incidence Rates for

Most Common Sites in Women

4.5

4.8

5.5

6.4

6.5

10.4

11.1

14.4

16.2

35.7

0 10 20 30 40

Esophagus

Lymphoma

Liver

Uterus

Ovary

Stomach

Lung

Colorectal

Cervix

Breast

Incidence rates (per 100,000)

World Age-adjusted Death Rates for Most

Common Sites in Men

3.6

3.8

3.9

4.3

8

8.8

9.8

14.4

15.6

31.4

0 10 20 30 40

Lymphoma

Bladder

Leukemia

Pancreas

Prostate

Esophagus

Colorectal

Liver

Stomach

Lung

Death rates (per 100,000)

World Age-adjusted Death Rates for Most

Common Sites in Women

2.8

3.3

3.7

3.8

5.5

7.6

7.8

8

9.5

12.5

0 5 10 15

Leukemia

Pancreas

Esophagus

Ovary

Liver

Colorectal

Stomach

Cervix

Lung

Breast

Death rates (per 100,000)

Estimated New Cancer Cases and Deaths by Sex, United States, 2012.

Estimated new cases and deaths from lung cancer ( USA) New cases: 219,440.

Deaths: 159,390. 5-year relative survival rate (1995 – 2001)= 15.7%. Local recurrence =49% Regional metastasis = 16% Distant metastasis = 2% (American Cancer Society.: Cancer Facts and Figures 2009)

American Cancer Society. Cancer Facts & Figures–2001

Ginsberg RJ, et al. Cancer: Principles and Practices of Oncology. 6th ed. 2001;925-983.

LUNG CANCER Risk factors—smoking

has been implicated in:

• 80% of lung cancer deaths in men

• 75% of lung cancer deaths in women

• 17% of lung cancer cases in nonsmokers

• 28% of all cancer deaths

35-year old male who smokes 25 cigarettes per day:

• 13% risk of dying from lung cancer before age 75

• 10% risk of dying from coronary disease

• 28% risk of dying from smoking-related disease

Smoking

Figlin RA, et al. Cancer Treatment. 1995;385-413.

Ginsberg RJ, et al. Cancer: Principles and Practices of Oncology. 6th ed. 2001;925-983.

LUNG CANCER Risk factors other than smoking

• Asbestos

• Radon (from mining or indoor exposure)

• Other “occupational carcinogens”

Chloromethyl ether

Chromium

Nickel

Arsenic

• Diet (vitamins A, C, E, -carotene deficiencies)

• Genetic/familial factors

NCCN guideline on lung cancer

screenining (version 1.2012)

• Risk factors for lung cancer

• Recommend high-risk for screening

• Evaluation & follow-up of nodules

• Accuracy of LDCT & image modalities

• Benefits & Risks of screening

Lung cancers screening : Risk asessments

a) encourage quit smoke

b) high radon exposure

c) lung carcinogen:

asbestos, arsenic, nickel,

beryllium, cadmium, chromium, sillica

diesel fumes

d) lung cancer, lymphomas, cancers of

head & neck, smoking-related cancers

e) Second hand smoke: variable exposure:

It is not independent risk factor for lung

cancer screening.

Recommendation for lung cancer screening

LDCT= Spiral(herical) Low-

dose computed tomography 100-120kVP & 40-60mAs

Additional risk factors:

cancer history,

lung disease history,

family history of lung cancer,

radon exposure, occupational exposure

High risk:

# Age 55-74 y and >30 pack

year history of smoking and

smoking cessation < 15 y

(category 1)

# Age > 50 y and >20 pack

year history of smoking and

one of additional risk

factors(other than second-

hand smoke)

(category 2B)

Risk status

Routine lung cancer screening is not recommended.

f evaluated mediastinum or lymph node prefered standard dose CT with contrast.

g benign pathern: calcification, fat in nodule, feathure suggested inflammatory process, multiple nodules

m new nodule > 3 mm in mean diameter

l rapid increase in size suspeced inflammatory process.

n PET/CT for lesion greater than 8 mm.

Risks/Benefits of lung cancer screening

WHO histologic classification of Lung Cancer (1999)

• Preinvasive lesion Squamous dysplasia/carcinoma in situ

Atypical adenomatous hyperplasia

Diffus idiopathic pulm.neuroendocrine cell hyperplasia

• Invasive malignant Squamous cell (papillary, clear cell, small cell, basaloid) (30%)

Small cell (combined SCLC) (15-20%)

Adenocarcinoma (acinar, papillary, bronchioloalveolar, solid with mucin formation, mucinous, signet ring, clear cell) (30-50%)

Large cell (neuroendocrine, basaloid, lymphoepithelioma-like, clear cell, large cell with rhabdoid phenotype) (5-10%)

Adenosquamous (1.5%)

Carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements(spindle,giant cell, carcinosarcoma, pulm. Blastoma)

Carcinoid tumor (typical,atypical) (1%)

Carcinomas of salvary gland type (mucoepidermoid, adenoid cystic)(0.1%)

Unclassified carcinoma

International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma in resection specimens

Pre-invasive lesions

• Atypical adenomatous hyperplasia(AAH)

• Adenocarcinoma in situ

(≤3 cm formerly BAC) =AIS

Nonmucinous

Mucinous

Mixed mucinous/nonmucinous

Minimally invasive adenocarcinoma

(≤3 cm lepidic predominant tumour,

with ≤5 mm invasion) = MIA

Nonmucinous

Mucinous

Mixed mucinous/nonmucinous

Invasive adenocarcinoma

• Lepidic predominant

(formerly nonmucinous BAC pattern,

with >5 mm invasion)

• Acinar predominant

• Papillary predominant

• Micropapillary predominant

• Solid predominant with mucin

production

• Variants of invasive adenocarcinoma

Invasive mucinous adenocarcinoma

(formerly mucinous BAC)

Colloid

Fetal (low and high grade)

Enteric

SCLC: Staging

• Limited Stage

tumor involvement of one lung, the mediastinum and ipsilateral and/or contralateral supraclavicular lymph nodes or disease that can be encompassed in a single radiotherapy port.

• Extensive Stage

Ihde DC, et al. Cancer: Principles & Practice of Oncology. 1997;911-948.

Lassen U, et al. Cancer Treatment. 1995;414-420.

Soriano AF, et al. Current Cancer Therapeutics. 1998;177-191.

SMALL CELL LUNG CANCER Survival by stage

Median Survival – Median Survival – 5-Year Survival

Untreated Patients Treated Patients (%)

(wk) (mo)

Limited disease 12 14-20 10%-20%

Extensive disease 5 8-12 3%-5%

NSCLC

Survival for Resected Patients (TMN staging 1986)

Stage Descriptors 5-yr Survival%

I T1-2 N0 M0 60 – 80

II T1-2 N1M0 25 – 50

IIIA T3 N0-1 M0

T1-3 N2 M0

25 – 40

10 – 30

IIIB Any T4 or

Any M3 M0

<5

IV Any M1 <5

Staging (1997) TNM Subset 5-year survival

Clinical staging Pathologic staging

IA T1N0M0 61% 67%

IB T2N0M0 38% 57%

IIA T1N1M0 34% 55%

IIIA T1-3N2M0 13% 23%

T3N1M0 9% 25%

IIIB T4N0-2M0 7% <10%

T1-4N3M0 3%

IV Any T Any N M1 1%

IIB T2N1M0 24% 39%

T3N0Mo 22% 38%

IASLC: analysis: NSCLC 68,463,SCLC 13,032 from 1990-2000……New Lung cancer staging 2010

• T1 ….. T1a (≤2 cm in size) & T1b (>2–3 cm)

• T2 …...T2a (>3–5 cm in size) & T2b (>5–7 cm)

• T2 (>7 cm in size) …..T3.

• Multiple tumor nodules in the same lobe = T4 ….T3

• Multiple tumor nodules in the same ~ different lobe = M1 ….T4

• M1 …..M1a & M1b.

• Malignant pleural and pericardial effusions = T4 …..M1a.

• Separate tumor nodules in the contralateral lung = M1a …..M1b

*Sarcomas and other rare tumors are not included

New lung cancer staging system(AJCC and UICC2010 )

for

NSCLC, SCLC Carcinoid tumors

Classification of visceral pleural invasion (VPI)

PL category Definition T status

PL0

Tumor within the subpleural

parenchyma or, invading

superficially into the pleural

connective tissue below the

elastic layer.

PL0 is not a T descriptor

and the T component

should be assigned on

other features.

PL1 Tumor invades beyond the elastic

layer.

pT2 Indicates

VPI

PL2 Tumor invades to visceral pleural

surface.

PL3 Tumor invades the parietal pleura. pT3

Classification of visceral pleural invasion (VPI)

The 7th edition of the “TNM Classification of Malignant Tumors”

new lung cancer staging system(AJCC and UICC2010 ) 6th ed 7th ed

N0 N1 N2 N3 T/M descriptors

T1 (=2cm) T1a IA IIA IIIA IIIB

T1 (>2 cm =3 cm) T1b IA IIA IIIA IIIB

T2 (>3 cm =5 cm) T2a IB IIA IIIA IIIB

T2 (>5 cm = 7 cm) T2b IIA IIB IIIA IIIB

T2 (>7 cm)

T3

IIB IIIA IIIA IIIB

T3 (direct invasion) IIB IIIA IIIA IIIB

T4 (same lobe nodules) IIB IIIA IIIA IIIB

T4 (extension) T4

IIIA IIIA IIIB IIIB

M1 (ipsilateral nodules) IIIA IIIA IIIB IIIB

T4 (pleural effusion) M1a

IV IV IV IV

M1 (contralateral nodules) IV IV IV IV

M1 (distant) M1b IV IV IV IV

Definitions of second primary, satellite nodules and metastasis

Type Definition

Satellite nodule

Same histology

And same lobe as primary cancer And no systemic metastasis

MPLCs

Same histology, anatomically separated

Tumors in different lobes And no N2-3 involvement And no systemic metastasis

Same histology, temporally separated

=4-yr interval between tumors

And no systemic metastasis from either tumor

Different histology

Or different molecular genetic features

Or arising separately from foci of CIS

Metastasis

Same histology With multiple systemic metastasis

Same histology, in different lobes

And presence of N2-3 involvement Or < 2-yr interval

Diagnosis

• Sputum cytology + 60-70%

• Bronchoscopy central lesion +90%

mid lung lesion +50%

Peripheral lesion +25%

• TNA or FNA under fluoroscopy or CT guide

sensitivity 75-80%, specificity 100%

result possibility cancer 20-30%

Non-Invasive Staging for Lung Cancer (ACCP:2007)

mediastinal lymph node metastasis?

sensitivity specificity

CT scan 51% 85%

PET scan 74 % 85%

EUS-guided FNA

With enlarged nodes on CT 90 % 97%

Without enlarged nodes on CT 58 %

EBUS 92 - 96 %

FDG-PET scan

False-negative ….. small tumors(<1cm)

False-positive …..benign inflammatory diseases

Unreliable for brain metastasis

For detection of mediastinal metastases:

sensitivity = 91%

specificity = 86%

For detecting distant metastases:

sensitivity = 82%

specificity = 93%

Invasive mediastinal staging

Mediastinoscopy Anterior Mediastinotomy (Chamberlain Procedure)

VATS

International Association for the Study of Lung Cancer

(IASLC) & European Society of Thoracic Surgeons

Systematic nodal dissection (SND): to dissect and

remove all mediastinal tissue containing the lymph

nodes within anatomic landmarks. Excision of at least

three mediastinal nodal stations, including the subcarinal

node, is recommended as a minimum requirement. “Systematic sampling” refers to a routine biopsy of lymph nodes at some levels of nodal station.

Lymphatic drainage of the lung

Lardinois D, De Leyn P, Van Schil P, et al. ESTS guidelines for intraoperative lymph node

staging in non-small cell lung cancer. EurJ Cardiothorac Surg 2006;30:787–792.

Performance Status Eastern Cooperative Oncology Group/ Zubrod Scale

0=minimal symptoms; fully functional

1= symptomatic; able to carry out all ordinary tasks

2= < or = 50% waking hours in bed

3= 50% waking hours in bed

4= bedridden; often moribund

Principles of surgical therapy of lung cancer

• Anatomic pulmonary resection

• Sublobar resection:

segmentectomy & wedged excision:

margin>2 cm.or > size of the nodule

N1-2 sampling if technical feasible(add no risk)

for poor lung reserve or major co-morbid

Peripheral nodule<2cm. With:

Pure AIS

Nodule has 50% ground glass on CT

a long doubling time(>400d) from Imaging

• VATS approach is acceptable. (no compromise standard

oncologic & dissection principles)

• Lung sparing anatomic resection(sleeve lobectomy

preferred over pneumonectomy) if complete resection.

• Enbloc resection for T3(extention) & T4 local invasion if potential complete resection.

• Pathology:close or positive margin:risk of local

recurrence

• N1-2 dissection(minimal three N2 sampling or complete

dissection)

Principles of surgical therapy of NSCLC

Principles of surgical therapy of NSCLC

• Complete resection:

systemic dissection or sampling

free margin

no extracapsular nodal extension

highiest mediastinal node negative

• Incomplete resection:

margin positive,

extracapsular nodal extension

unremoved positive nodes

positive pleural or pericardial effusions

• R0 = complete resection

• R1 = microscopic positive resection • R2 = macroscopic residaul tumors

Post NSCLC resection management

• Pathologic stage II or greater:

should be referred to medical oncologist for evaluation.

• Consider referral to medical oncologist for

resected stageIB.

• Consider referral to radiation oncologist for resected stageIIIA.

The role of surgery in stageIIIA (N2 dis).

• ?N2…Radiologic & invasive staging before Rx.

• EUS/EBUS before Rx

• Intraop. Occult N2: standard resection.

• Mediastinoscopy before planned resection

• Single node size < 3 cm may considered resection.

• PET/CT for restaging after induction therapy.

• Negative mediastinum after neoadjuvant Rx: better prognosis

• After neoadjuvant Rx:evaluation of the mediastinum

Radiographic methods ..unreliable

EBUS(+/-EUS) for pre treatment evaluation

Remediastinoscopy is difficult & lower accuracy.

Reserve mediastinoscopy for nodal restaging

Principles of surgical therapy of SCLC

• Stage I, SCLC < 5% of all SCLC

• Staging > IB, do not benefit from surgery.

• Stage I should undergo standard evaluation &

invasive mediastinal staging before surgery.

• PCI(Prophylatic cranial irradiation) can improve

disease-free & overall survival.

• PCI is not recommended in poor performance

status & impaired mental function. Standard evauation= CT chest,upper abdomen,brain imaging,PET/CT

Postop.complete resection: without nodal metastasis …potop. Chemotherapy.

with nodal metastasis…concurrent chemo-radiation.

Early stage Lung cancer:

severe dysplasia,

carcinoma in situ (CIS),

carcinoma in sputum cytology(normal CXR)

Treatment: Photodynamic therapy under autofluorescent bronchoscopy guide

Superficial squamous cell carcinoma who are not surgical candidates

Treatment: photodynamic therapy,

electrocautery,

cryotherapy, brachytherapy

Diagnosis and Management of Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)2007

clinical stage I and II NSCLC

surgical resection:

conventional surgical resection,

lobectomy or greater resection (1A)

comorbid disease or decreased pulmonary

function, sublobar resection is recommended (1B) stage I and II NSCLC, it is recommended

that intraoperative systematic mediastinal

lymph node sampling or dissection be per- formed for accurate pathologic staging. (1B)


stage I NSCLC the use of VATS by surgeons

experienced in these techniques is an acceptable

alternative to open thoracotomy.(1B)

centrally or locally advanced NSCLC in whom a

complete resection can be achieved with either tech-

nique, sleeve lobectomy is recommended over pneumonectomy.(1B)


completely resected stage IA NSCLC, the use of

adjuvant chemotherapy is not recommended for

routine use outside the setting of a clinical trial.(1A) completely resected stage IB NSCLC, the use of

adjuvant chemotherapy is not recommended for routine use. (1B)


In NSCLC patients with N2 disease identified

preoperatively (IIIA), induction therapy followed by

surgery is not recommended except as part of a clinical

trial.(1C)

Post induction chemoradiotherapy for stageIIIA,N2 dis. Pneumonectomy is not recommended.(1B) Incomplete resection of stageIIIA,N2 dis.

Postoperative platinum-based chemoradiotherapy is recommended. (1C)


In selected patients with clinical T4N0-1 NSCLC due to

satellite tumor nodule(s) in the same lobe, Surgery is

not recommended if there is N2 involvement.. (1C)

StageIIIB,T4(satellite)N0, no mediastinal or distant

metastasis: Lobectomy is the recommended.(1B)


Pancoast tumor with mediastinal nodes or distant

metastasis is contraindicated to resection.(1C)

Potential resectable, nonmetastatic Pancoast tumor

with good PS

Preop. concurrent chemoradiotherapy is recommended prior to resection.(1B) Complete or incomplete resected Pancoast tumor:

postoperative radiotherapy is not recommended

because of no survival benefit.(2C)


Intraoperative found a second cancer in a different lobe,

resection of each lesion is recommended.(1C)

Metachronous NSCLC with mediastinal nodes metastasis is a contraindication to resection.(1C)


Isolated brain metastasis with mediastinal nodes involvement is

a contraindication to resection. (1C)

In resectable N0,1 or previously complete resected primary

NSCLC with isolated brain metastasis:

Resection or radiosurgical ablation of an isolated brain

metastasis is recommended.(1C)

After curative resection of an isolated brain metastasis,

adjuvant whole-brain radiotherapy is suggested.(2B)

After curative resections of both the isolated brain metastasis

and the primary tumor, adjuvant chemotherapy may be

considered.(2C)


Isolated adrenal metastasis with mediastinal nodes

metastasis is a contraindication to resection.(1C)

In resectable N0,1 primary NSCLC, with isolated adrenal

metastasis:

Resection of both primary tumor and adrenal metastasis

is recommended.(1C) Isolated adrenal metastasis in previously complete

resected primary NSCLC and disease-free interval is > 6

months:

Resection of an isolated adrenal metastasis is recommended.(1C) Diagnosis and Management of Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)2007

In suspected BAC who are good surgical candidates

and CT shows a pure ground-glass appearance:

Sublobar resection may be appropriate if intraoperative

pathologic confirms pure BAC without evidence of invasion, and surgical margins are free of disease.(1B) In stage I,SCLC who are being considered for curative

resection:

Invasive mediastinal staging and extrathoracic imaging

(head CT/MRI, abdominal CT plus bone scan) followed

by a platinum-based chemotherapy should be offered.

(1A) Diagnosis and Management of Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)2007

1. VATS can be recommended to reduce overall postoperative

complications ( IIa, level A ).

2. VATS can be recommended to reduce pain and overall

functionality over the short term ( IIa, level B ).

3. VATS can be recommended to improve delivery of adjuvant

chemotherapy delivery ( IIa, level B ).

4. VATS can be recommended for lobectomy in clinical stage I and

II NSCLC patients, with no proven difference in stage-specific

5-year survival compared with open thoracotomy ( IIb, level B ).

Robert J. Downey, Davy Cheng,Kemp Kernstine,Rex Stanbridge,Hani Shennib,Randall Wolf,Toshiya Ohtsuka,Ralph Schmid,David Waller, Hiran Fernando,Anthony Yim,and Janet Martin (Innovations 2007;2: 293–

302)

A Consensus Statement of ISMICS 2007 Video-Assisted Thoracic Surgery for Lung Cancer Resection

VATS versus Open Thoracotomy: A Comparison

THORACOTOMY VATS

Size of incision 10-14 inches approx. 1 inch

Average hospital stay 10-12 days Less than 2 days

Return to work/normal routine 6-8 weeks 7-10 days

Major Complications 30 percent less than 5 percent

http://www.ctsnet.org/graphics/experts/Thoracic/Yim/Fig3a_large.jpg

http://www.ctsnet.org/graphics/experts/Thoracic/Yim/Fig3b_large.jpg

http://www.ctsnet.org/graphics/experts/Thoracic/Yim/Fig3c_large.jpg

Less postop. Pain

Shorten hospiyal stay

Rapidly recover

Cosmetic Minimal trauma immunological advantage

Simultaneous Stapling lobectomy

The Valley Hospital New Jersy

Open? or VATS?

Multiple or Single port VATS? Rib spreading or Not?

common diseases of the lung and pleural cavity · ginsberg rj, et al. cancer: principles and...

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