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