¼±Åà - È­»ìǥŰ/¿£ÅÍŰ ´Ý±â - ESC

 

Lung cancer

1. °³¿ä

55-65¼¼¿¡ peak incidence¸¦ º¸ÀÌ¸ç ³²ÀÚ¿¡¼­ 25³âÀüºÎÅÍ ½ÃÀÛµÈ ±Ý¿¬³ë·ÂÀ¸·Î

Æó¾ÏÀ¸·Î ÀÎÇÑ age-adjusted cancer death rate´Â ´À·ÁÁö°í ÀÖ´Ù. ±×·¯³ª ºÒÇàÈ÷µµ

¿©¼º¿¡¼­´Â ¿ÀÈ÷·Á Áõ°¡Çϰí ÀÖ´Ù.

Áø´Ü´ç½Ã ´ÜÁö 15%¿¡¼­¸¸ local diseaseÀ̰í 25%´Â regional LN(+), 55%À̻󿡼­ distant

metastasis¸¦ º¸ÀδÙ.

* 5YSR

local disease = 50%

regional node = 20%

overall = 14%

5³â »ýÁ¸·üÀÌ 30³â »çÀÌ¿¡ 2¹è·Î Áõ°¡ÇÏ¿´´Âµ¥ ÀÌ´Â combined-modality tx°¡ ¹ßÀüÇÏ¿´±â

¶§¹®ÀÌ´Ù.

2. º´¸®

* WHO classification

i) squamous or epidermoid carcinoma

ii) small cell(=oat cell) carcinoma

iii) adenocarcinoma(including bronchioloalveolar)

iv) large cell carcinoma

- epidermoid & small cell ca : endobronchial growth

- adenoca & large cell ca : peripheral nodules or mass, pleural involvement

* Bronchioloalveolar carcinoma(BAC)

adenocarcinomaÀÇ subtypeÀ¸·Î clara cell(nonciliated bronchiolar epithelial cell)¿¡¼­

±â¿øÇÑ´Ù.

bronchioloalveolar epithelium¿¡¼­ »ý±â³ª mucous gland¿¡¼­ »ý±æ¼öµµ ÀÖ´Ù.

preexisting scar¿Í °ü·ÃÀÖÀ¸¸ç bronchogenic spreadÇÏ¿© multiple pul. nodulesÀ»

³ªÅ¸³½´Ù.

peripheral locationÇϸç mass°¡ Ä¿Áú¶§±îÁö Áõ»óÀÌ ¾ø´Ù.

ÀÏÂï Ç÷¾×°ú LN¸¦ ħ¹üÇϰí Áõ»óÀ» ÀÏÀ¸Å°±â Àü¿¡ ÀüÀ̰¡ »ý±â±â ½±´Ù.

: pleural invasion, scalene LN metastasis

- ´ã¹è¿ÍÀÇ °ü·Ã¼ºÀº controversial.

3. ¿øÀÎ

¨ç cigarette smoking

2PPD ¡¿ 20 yr : nonsmokerº¸´Ù cancer risk°¡ 60-70¹è ´õ ³ô´Ù.

±Ý¿¬ÀÌ ¾î·Á¿î ÀÌÀ¯´Â nicotine addictionµÇ±â ¶§¹®ÀÌ´Ù.

±Ý¿¬À» Çϸé Á¡Â÷ cancer risk°¡ ÁÙ¾îµéÁö¸¸ nonsmoker level±îÁö ¶³¾îÁöÁø ¾Ê´Â´Ù.

¨è oncogene

i) K-ras : adenocarcinoma

ii) myc family(c-, N-, L-)

c-myc change : Non-SCLC

all myc family : SCLC

iii) bcl-2, Her-2/neu, telomerase gene overexpression

cf. ras gene mutation : Non-small cell caÀÇ poor Px

c-myc gene amplification : small cell caÀÇ poor Px

¨é tumor suppressor gene

p53 & rb gene mutation : SCLCÀÇ 90%À̻󿡼­

4. ÀÓ»ó ¹ßÇö

1) Pancoast's(=sup. sulcus tumor, T3) syndrome

lung apex¿¡ epidermoid cancerÀÇ local extension¿¡ ÀÇÇÏ¿© C8, T1, T2 nerve¸¦ ħ¹ü.

±× °á°ú shoulder pain, ulnar radiating pain, 1st, 2nd ribÀÇ radiographic destructionÀ»

À¯¹ß.

Horner's syndrome°ú µ¿¹ÝµÇ±âµµ ÇÑ´Ù.

<Ä¡·á>

RTx + sugeryÀÇ combination Tx

preop staging(mediastinoscopy & CT)

-> tumor extent°áÁ¤, neurologic exam(NCV)

¸¸¾à mediastinoscopy (-)¶ó¸é µÎ°¡ÁöÀÇ ±ÙÄ¡Àû Á¢±ÙÀÌ °¡´ÉÇѵ¥

i) 3000 cGy/10ȸÈÄ 3-6ÁÖÈÄ en bloc resection

=> 3YSR = 42%(epidermoid ca), 21%(adeno, large cell ca)

ii) RTx alone

combination tx¿Í survival rate ºñ½ÁÇÏ´Ù.

2) SVC syndrome - SVC syndromeÆí ÂüÁ¶

3) pericardial & cardiac extension with resultant tamponade

arrhythmia or cardiac failure

lymphatic obstruction with resultant pleural effusion

lymphangitic spread through the lung with hypoxemia & dyspnea

4) Extrathoracic metastatic ds

autopsy»ó epidermoid ca >50%

adenoca : 80%

small cell ca :85%

5) Paraneoplastic syndromes

¨ç systemic sx : anorexia, cachexia, wt loss(>30%), fever, suppressed immunity

¨è endocrine syndrome(12%)

PTH or PTH-related peptide(squamous) -> Ca¡è, P¡é

SIADH or ANP(small cell) -> Na¡é

ACTH(small cell) -> ectopic cushing

¨é skeletal-connective tissue syndromes

clubbing(30%) - nonsmall cell

hypertrophic pul. osteoarthropathy(1-10%) - adenoca

¨ê neurologic-myopathic syndrome(1%)

Eaton-Lambert syndrome & retinal blindness (small cell)

peripheral neuropathy, subacute cerebellar degeneration,

cortical degeneration, polymyositis(all type)

¨ë coagulation, thrombotic, or other hematologic syndrome(1-8%)

migratory venous thrombophlebitis(Trousseau's syndrome)

nonbacterial thrombotic(marantic) endocarditis with arterial emboli

DIC with hemorrhage

anemia

granulocytosis, leukoerythroblastosis

¨ì cutaneous manifestation

dermatomyositis & acanthosis nigricans(¡Â1%)

renal manifestation of nephrotic syndrome or glomerulonephritis(¡Â1%)

5. Áø´Ü ¹× º´±â

1) Early diagnosis

high risk(45¼¼¡è, 40 cigarette/day¡è) + asymptomatic person¿¡¼­

sputum cytology & CXR·Î screeningÇÏ¿´À» ¶§ »ýÁ¸·ü Çâ»óÀÌ ¾ø¾ú´Ù.

ºñ·Ï screening´ç½Ã¿¡ 90%¿¡¼­ ¹«Áõ»óÀ̾úÁö¸¸ »ýÁ¸·üÀº nonscreened group°ú

Â÷À̰¡ ¾ø¾ú´Ù.

low dose spiral CT°¡ ´õ sensitiveÇÏÁö¸¸ false positive rate°¡ ³ô´Ù.

(25%°¡ abnormal test, ÀÌÁß 10%¸¸ÀÌ cancer)

Lung cancer screeningÀÇ survival benefit´Â ¾ÆÁ÷ ¾Ë·ÁÁöÁö ¾Ê°í ÀÖ´Ù.

2) Tissue diagnosis

i) FOB with biopsy

ii) mediastinoscopy¸¦ ÅëÇÑ node Bx

iii) surgical resection½Ã operative specimen

iv) percutaneous biopsy

v) fine-needle aspiration

vi) cell block(mal. effusion)

3) Staging

i) anatomic staging : resectability(lobectomy or pneumonectomy)

ii) physiologic staging : operability

(1) NSCLC : TNM staging system(Tab 88-3)

Áø´Ü½Ã 1/3 - curative tx°¡´ÉÇÒ Á¤µµ·Î localize(stage I, II, IIIAÀϺÎ)

1/3 - local or regional ds(IIIAÀϺÎ, IIIB)

1/3 - distant metastasis(IV)

(2) SCLC

¨ç Limited stage(30%) - one hemithorax & regional LN(mediastinal, contralateral hilar,

ipsilateral supraclavicular node)

limited stage¶õ tolerable RT port³»¿¡ tumor°¡ Á¸ÀçÇÒ¶§¸¦ ¸»ÇÑ´Ù. µû¶ó¼­

i) contralateral supraclavicular node

ii) recurrent laryngeal N. involve

iii) SVC obstructionÀº limited stageÀÌ´Ù.

¨è Extensive state(70%)

cardiac tamponade, malignant pleural effusion, bilateral pul. parenchymal involvement

(Àå±âµéÀÌ curative RT dose¿¡ tolerableÇÏÁö ¸øÇϹǷΠextensive stage¿¡ Æ÷ÇÔÇÑ´Ù)

4) General staging procedures

¨ç Hx, P/E, other medical problemÆò°¡, performance status, wt loss Hx

chest & abdomen CT½ÃÇà

PET : metastatic ds detectÇϴµ¥ sensitive

¨è BFS

¨é CXR & CT scan : tumor size, nodal involvement

old CXR : ºñ±³Çϴµ¥ À¯¿ë

CT : preop staging

- mediastinal node detect, pleural extension, occult abd ds(liver, adrenal gl),

curative RT planning(RT field decision)

¨ê mediastinoscopy

mediastinal nodal involvement°¡ Ä¡·á°áÁ¤¿¡ ¿µÇâÀ» ¹ÌÄ£´Ù¸é Á¶Á÷ÇÐÀûÀ¸·Î Áõ¸íµÇ¾î¾ß

ÇÑ´Ù.±×·¯¹Ç·Î LN sampleÀ» À§ÇØ mediastinoscopy or thoracoscopy¸¦ ½ÃÇàÇÏ¿© N2 or

N3 nodal involvementÀ¯¹«¸¦ È®Á¤ÇÒ¼ö ÀÖ´Ù.

¡Å clinical stage I, II, III NSCLCȯÀÚ¿¡¼­ curative surgical approach¸¦ °í·ÁÇÒ ¶§ ÇʼöÀûÀÌ´Ù.

¨ë small cell lung cancer¿¡¼­ÀÇ CT

RT planning, Ä¡·á¹ÝÀÀ Æò°¡

Ä¡·áÈÄ¿¡ tumor recurrence¸¦ º¸´Âµ¥ Áß¿ä

¨ì Brain CT or bone scan

sx & signÀÌ ÀÖ°í X-ray¿¡¼­ Àǽɽº·¯¿ï ¶§ ½ÃÇà

5) Staging of SCLC

i) Chest & abdominal CT ¡ñhepatic & adrenal involvement¡è

ii) Bronchoscopy with washings & Bx

iii) BRCT(10%¿¡¼­ meta)

iv) BM biopsy & aspiration : 20-30%¿¡¼­ meta(+)

v) Bone scan : Áõ»óÀÌ Àְųª ÀÇ½ÉµÉ ¶§ ½ÃÇà

* Spinal cord compression or leptomeningitis sx & sign(+)

=> spinal CT or MRI & CSF cytology½ÃÇàÇÏ¿© malignant cellÀÌ ³ª¿À¸é

RTx & intrathecal CTx(MTX)½ÃÇà.

6) Resectability & operability°áÁ¤

(1) Major contraindications of curative surgery or RT alone(NSCLC)

¨ç extrathoracic metastasis

¨è SVC syndrome

¨é vocal cord, phrenic N. paralysis

¨ê malignant pleural effusion

¨ë cardiac tamponade

¨ì carina·ÎºÎÅÍ 2cmÀ̳»(op·Î´Â not curable, but RT·Î´Â curable)

¨í contralateral lung metastasis

¨î bilateral endobronchial tumor(potentially curable by RT)

¨ï supraclavicular LN metastasis

¨ð contralateral LN metastasis

¨ñ main pul. a. involvement

(2) SCLC

´ëºÎºÐ unresectableÇÏÁö¸¸ resection°¡´ÉÇÏ´Ù¸é °í·ÁÇØº¼¼ö ÀÖ´Ù. (peripheral)

7) Physiologic staging

lung caȯÀÚ´Â ´Ù¸¥ medical problem»Ó¸¸ ¾Æ´Ï¶ó COPD¿Í °ü·ÃÇÑ ¹®Á¦, cardiopulmonary

problemÀ» °¡Áö°í ÀÖ´Ù.

preop conditionÀ» Çâ»ó½Ã۱â À§ÇØ ±³Á¤°¡´ÉÇÑ ¹®Á¦µé(anemia, electrolyte, fluid

disorders, infection, arrythmia)À» ±³Á¤ÇÑ´Ù.

Stop smoking

* thoracic surgeryÀÇ absolute CIx

i) nonambulatory performance status

ii) recent MI(<3mo) : ´ë·« 20%°¡ reinfarctionÀ¸·Î »ç¸Á,

6°³¿ù ÀÌ»ó Áö³­ past infarctionÀº relative CIx

* Other major CIx

i) uncontrolled major arrythmia

ii) maximum breathing capacity < 40%

iii) FEV1 < 1L

iv) CO2 retention(hypoxemiaº¸´Ù ´õ serious)

v) severe pul. hypertension

FEV1ÀÌ 1.1 ¡­ 2.4L : Á¶½É½º·± ÆÇ´Ü

FEV1 > 2.5L : pneumonectomy°¡´É

* borderline PFT, pul HTNÀǽɵǴ ȯÀÚ¿¡¼­

Ventilation-Perfusion scanÀ» ½ÃÇàÇÏ¿© physiologic operability¸¦ °áÁ¤ÇÒ¼ö ÀÖ´Ù.

ant & post. view¿¡¼­ °¢°¢ lungÀ» ÇÕÇÏ¿©

normal/total lung capacity ratio ¡¿ FEV1 > 1LÀ̸é pneumonectomy¿¡ tolerable

6. Ä¡·á Tab 88-5

1) NSCLC - localizing disease

¨ç Surgery

i) IA, IB, IIA, IIB(T2N1M0, T3N0M0) : pul resectionÀÌ choice

ii) IIIA : age, cardiopul fx, anatomy¸¦ °í·ÁÇÏ¿© °áÁ¤, resection°¡´ÉÇÏ´Ù¸é °í·Á.

complete resection½Ã 5YSR = 50%(N1 disease), 20%(N2 disease)

½ÇÁ¦ ´ëºÎºÐÀº N2ÀÌ´Ù.

* N2 disease¿¡ ´ëÇØ¼­ ¼ö¼úÀº controversialÇÏ¸ç ´ÙÀ½°ú °°ÀÌ 2 groupÀ¸·Î ³ª´­¼ö ÀÖ´Ù.

¤¡. "minimal" disease(only one node with microscopic foci)

¤¤. "advanced" bulky disease(more common) => CT»ó definite lesion, preop¿¡ ¹ß°ß

iii) N3 disease

contralateral or bilateral mediastinal node, extracapsular nodal involve or fixed node´Â

¼ö¼úÀÇ °í·Á´ë»óÀÌ ¾Æ´Ï´Ù.

chest wall direct extensionÀÇ °æ¿ì resection, carina±ÙóÀÇ °æ¿ì¿¡´Â tracheal sleeve

pneumonectomy, and sleeve lobectomy¸¦ ½ÃµµÇÒ¼ö ÀÖ´Ù.

iv) unresectable disease¿¡ ´ëÇÑ neoadjuvant (preoperative) chemotherapy

response rate 50-60%

¸¹Àº ȯÀÚ¿¡¼­ unresectable ds¸¦ resectable ds·Î Àüȯ½ÃŲ´Ù.

v) VATS(video-assisted thoracic surgery)

curative lung ca resectionÀ» À§Çؼ­ ÈçÈ÷ »ç¿ëµÇÁø ¾ÊÁö¸¸ poor lung fx°¡Áø peripheral

lesion¿¡ ´ëÇØ¼­ »ç¿ëÇÒ¼ö ÀÖ´Ù.

¨è occult & stage 0 carcinoma management

malignant cellÀÌ sputumÀ̳ª bronchial washing¿¡¼­¸¸ ¹ß°ßµÇ°í

CXR or CT»ó¿¡¼­ Á¤»óÀÏ ¶§ º´º¯À» localizeÇØ¾ß ÇÑ´Ù.

Àü½Å¸¶ÃëÇÏ¿¡ FOB·Î ÀÏ·ÃÀÇ differential brushing & Bx¸¦ ÅëÇÏ¿© 90%À̻󿡼­

º´º¯À» localizeÇÒ¼ö ÀÖ´Ù.

i) ÇöÀç recommendations

ºñ·Ï bronchial marginÀÌ positiveÀÌ´õ¶óµµ conservative surgical resection

(cancer remove & lung parenchyma conservation)

5YSR = ¡­60%

ÀÌÈÄ close F/UÇØ¾ß ÇÑ´Ù(¡ñ 2nd primary lung cancer incidence¡è, 5%/¸Å³â)

ii) one approach to in situ or multicentric lesions

= systemically administrated hematoporphyrin(tumor¿¡ localize & light sensitizer)

(Bronchoscopic phototherapy)

¨é SPN PET : 1.5cmÀÌ»óÀÏ ¶§ À¯¿ë

* Histologic diagnosis°¡ ÇÊ¿äÇÑ °æ¿ì

i) cigarette smoking Hx(+)

ii) 35¼¼ ÀÌ»ó

iii) relatively large lesion,

iv) calcification(-)

v) chest sx(+)

vi) associated atelectasis, pneumonitis or adenopathy

vii) old X-ray¿¡ ºñÇØ growth

* benign nature¸¦ ½Ã»çÇÏ´Â only 2 radiographic criterias

i) 2³âÀÌ»ó growth(-)

ii) Ư¡ÀûÀÎ calcification

: dense central nidus, multiple punctate foci, "bull's dye(granuloma),

"popcorn ball"(hamartoma)

¡Ø calcification´Üµ¶À¸·Î´Â malignancy¸¦ ¹èÁ¦ÇÏÁö ¸øÇÑ´Ù.

- 35¼¼ ¹Ì¸¸ÀÇ nonsmoker

= 3°³¿ù °£°ÝÀ¸·Î serial CT f/u -> ±×ÈÄ ¸Å³â

growth(+) -> Á¶Á÷Áø´Ü

- 35¼¼ ÀÌ»óÀ̰ųª smoking Hx(+)

= ¹Ù·Î Á¶Á÷ Áø´Ü

¨ê RT with curative intent

Stage III : 6%¿¡¼­ cure, 55-60Gy

* CHART(continuous hyperfractionated accelerated radiation therapy)

: 1.5Gy ¡¿ 3ȸ/day ¡¿ 12ÀÏ ¿¬¼Ó

=> 2YSR = 20-29%

¨ë combined-modality tx with curative intent

¨ì disseminated NSLCL

NSCLCÀÇ 70%°¡ unresectable -> poor prognosis

performance score: O(asymptomatic) 34ÁÖ

1(symptomatic, fully ambulatory) 25ÁÖ

2(in bed < 50%) 17ÁÖ

3(in bed > 50%) 18ÁÖ

4(bed ridden) 4ÁÖ

Áõ»óÀ» À¯¹ßÇÏ´Â primary tumor´Â primary tumor¿¡ ´ëÇØ RT¸¦ ½ÃÇàÇØ¾ß ÇÑ´Ù.

¿¹> bronchial obstruction with pneumonitis, hemoptysis, upper airway or SVC

obstruction

** RT°¡ Áõ»óÈ£Àü¿¡ µµ¿òÀÌ µÇ´Â °æ¿ì

hemoptysis(84%), SVC obstruction(80%), dyspnea(60%), atelectasis(6%),

cardiac tamponade(pericardiocentesis + RT), painful bony metastasis(66%),

brain or spinal cord compression(RT + dexa 25-100ng/d #4),

brachial plexus involvement

2) Small cell lung ca

combination CTx·Î median survival rate = 40-70ÁÖ

initial response : Ä¡·á½ÃÀÛÈÄ 6-12ÁÖ¿¡ °áÁ¤

¨ç CTx : 3ÁÖ °£°ÝÀ¸·Î 4-6 cycles

etoposide + cisplatin or carboplatin

other active regimen = etoposide, cisplatin & paclitaxel

¿ë·®À» Áõ·®Çϸé toxicity´Â Áõ°¡Çϳª survival benefit´Â ¾ø´Ù.

* oral etoposide : ³ëÀÎÀ̳ª very poor performance status¶§ initial tx·Î clinical benefitÀÌ

ÀÖ´Ù.

¨è Radiotherapy

i) Brain metastasis : high dose(40Gy) radiotherapy

ii) complete responseȯÀÚ¿¡¼­ÀÇ PCI(prophylactic crainal irradiation)

brain metastasis¸¦ ÀǹÌÀÖ°Ô °¨¼ÒÇÏ¿´À¸³ª »ýÁ¸·üÀÇ Çâ»óÀº ¹Ì¹ÌÇÏ¿´´Ù(5%)

(PCI¹ÞÁö ¾ÊÀº ȯÀÚ¿¡¼­ 2³âÀÌÈÄ 60-80%¿¡¼­ brain metastasis°¡ ¹ß»ýÇÏ¿´´Ù)

¨é combination-modality tx