Download Lung Cancer

Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung Cancer
台北榮總肺癌診療共識
V.2.0 2008
台北榮總肺癌團隊
Revised on 2008/02/25
Released on 2008/03/17
台北榮總肺癌團隊
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
台北榮總肺癌團隊
Lung Cancer
台北榮總肺癌多專科團隊核心人員
彭瑞鹏
蔡俊明
李毓芹
賴信良
陳育民
邱昭華
胸外
許文虎
吳玉琮
放射
許明輝
吳美翰
病理
周德盈
李永賢
放療
顏上惠
陳一瑋
胸腔
內科
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung Cancer
台北榮總肺癌團隊
Lababede, O. et al. Chest 1999;115:233-235
NSCLC
TNM
Staging
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
台北榮總肺癌團隊
Lung Cancer
Regional Lymph Node Classification for Lung Cancer Staging
How to Approach
- Mediastinoscopy
- EUS-FNA
- EBUS-TBNA
-VATS
- Extended mediastinoscopy
- Mediastinotomy
- VATS
- Mediastinoscopy; EUS-FNA, EBUS-TBNA
- EUS-FNA
- VATS
- EBUS-TBNA
- VATS (limited to 10 and 11)
N1=Ipisilateral hilar nodes
N2=Subcarinal, ipisilateral mediastinal nodes
N3=Contralateral hilar/ mediastinal, or
supraclavicular or scalene nodes
EUS: Endoscopic Ultrasound; EBUS: Endobronchoscopic ultrasound; FNA: Fine
Needle Aspiration; TBNA: Transbronchoscopic Needle Aspiration; VATS: Video
Clifton F. Mountain, CHEST1997
Assisted Thoracoscopic Surgery
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung Cancer
台北榮總肺癌團隊
Summary of Evaluation and Treatment
• PFT: Necessary for all operable stages
• PET (PET/CT) : recommend for all clinical stages, except
– stage IV, disseminate M1
• Mediastinoscopy: recommend for all clinical stages, except
– Peripheral T1
– Stage IV, disseminate M1
• Brain MRI: recommend for
– Stage II T1-2, N1, non-squamous histology
– Stage II T3, N0
– All stage III
– Stage IV, solitary M1
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
台北榮總肺癌團隊
Lung Cancer
Routine PET plus selective Mediastinoscopy
- Stage I and II (T1-2 N0-1) lesion
Chest CT scan
PET
Central located tumor or
mediastinal nodes > 1cm
Mediastinal nodes uptake
and
or
Negative
Positive
Mediastinoscopy
negative
Surgical resection
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung Cancer
Stage IIIA (T1-3, N2)
Stage IIIB (T4, N0-1)
台北榮總肺癌團隊
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung Cancer
台北榮總肺癌團隊
 正子掃描（PET/CT SCAN）：肺癌clinical stage 的pretreament workup，至於安排時間點是在胸腔電腦斷層
（chest-CT）後。
 除非Chest CT或PET SCAN都無縱膈腔異常發現且主要病
灶在週邊(peripheral IA lesion)可以不做縱膈腔鏡外，否則
縱膈腔鏡仍是評估縱膈腔淋巴結的gold standard
 Brain MRI取代brain CT建議在clinical stage II
nonsquamous cell type及stage III以上的病人安排。
 術中病理檢查若有R1 (microscopic residual tumor) 或
R2(macroscopic residual tumor)，應視實際情形考慮
reresection /（+chemotherapy）或是chemoradiation /
（+ chemotherapy）。
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
NSCL-1
Lung Cancer
台北榮總肺癌團隊
From NCCN guideline, V.2.2008
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
NSCL-2
Lung Cancer
台北榮總肺癌團隊
From NCCN guideline, V.2.2008
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
NSCL-3
Lung Cancer
台北榮總肺癌團隊
From NCCN guideline, V.2.2008
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
NSCL-4
Lung Cancer
台北榮總肺癌團隊
From NCCN guideline, V.2.2008
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
NSCL-5
Lung Cancer
台北榮總肺癌團隊
From NCCN guideline, V.2.2008
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
NSCL-6
Lung Cancer
台北榮總肺癌團隊
From NCCN guideline, V.2.2008
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
NSCL-7
Lung Cancer
台北榮總肺癌團隊
From NCCN guideline, V.2.2008
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
NSCL-8
Lung Cancer
台北榮總肺癌團隊
From NCCN guideline, V.2.2008
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
NSCL-9
Lung Cancer
台北榮總肺癌團隊
From NCCN guideline, V.2.2008
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
NSCL-10
Lung Cancer
台北榮總肺癌團隊
From NCCN guideline, V.2.2008
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
NSCL-11
Lung Cancer
台北榮總肺癌團隊
From NCCN guideline, V.2.2008
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
NSCL-12
Lung Cancer
台北榮總肺癌團隊
From NCCN guideline, V.2.2008
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
NSCL-13
Lung Cancer
台北榮總肺癌團隊
From NCCN guideline, V.2.2008
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
NSCL-14
Lung Cancer
台北榮總肺癌團隊
From NCCN guideline, V.2.2008
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
NSCL-15
Lung Cancer
台北榮總肺癌團隊
From NCCN guideline, V.2.2008
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung Cancer
台北榮總肺癌團隊
PRINCIPLES OF SURGICAL RESECTION
•
•
•
•
•
非緊急狀況下，術前所需影像學檢查應完備。
是否可切除(resectablility)之決定建議應由有經驗之胸腔腫
瘤外科醫師來決定。
如生理狀況許可(physiologically feasible) ，應採取
lobectomy或pneumonectomy。
如生理狀況受限制(physiologically compromised) ，應採
局部切除(Limited resection-segmentectomy or wedge
resection) 。
在不違背標準腫瘤手術原則下，可採用VATS (Videoassisted thoracic surgery) 。
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung Cancer
台北榮總肺癌團隊
PRINCIPLES OF SURGICAL RESECTION
•
N1&N2 node resection and mapping (minimum of three
N2 stations sampled or complete lymph node dissection)
•
如內科狀況無法開刀(medically inoperable) ，clinical
stage I& II病人應接受potential curative radiotherapy。
•
假如解剖位置適當與邊緣可切除乾淨(anatomically
appropriate and margin-negative resection) ，採取肺葉
保存術式比全肺切除好( lung sparing anatomic resectionsleeve lobectomy preferred over pneumonectomy) 。
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung Cancer
台北榮總肺癌團隊
PRINCIPLES OF PATHOLOGICAL REVIEW
•
•
•
•
Pathological review的目的包括:
classify lung cancer; determine the extent of invasion;
establish status of cancer involvement of surgical
margins; determine molecular abnormalities (EGFR)
所有手術病理報告都應該有肺癌WHO分類。
Bronchioloalveolar carcinoma (BAC): 越來越多證據顯
示EGFR mutation與bronchioloalveolar differentiation相
關；Pure BAC應無stroma、pleura與lymphatic spaces
之侵犯。
Nonmucinous BAC: TTF-1 (+) CK7 (+) CK20 (-)
Mucinuous BAC: TTF-1 (-) CK7 (+) CK20 (+)
TTF-1: Thyroid transcription factor-1
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung Cancer
台北榮總肺癌團隊
PRINCIPLES OF PATHOLOGICAL REVIEW
•
•
•
•
TTF-1對區分原發或轉移肺腫瘤很重要。大部分原發肺腫瘤
TTF-1為陽性，轉移為陰性反應。
Primary lung adenocarcinoma: TTF-1(+) CK7(+) CK20(-)
Metastatic colorectal carcinoma: TTF-1(-) CK7(-) CK20(+)
EGFR mutation之有無與預後相關；如TKI 對exon19
deletion效果良好。
K-ras與吸煙相關；K-ras與EGFR mutation為mutually
exclusive；亦即有K-ras mutation對TKI治療效果不佳(Kras with intrinsic resistance to TKI) 。
TKI: Tyrosine Kinase Inhibitor
EGFR: Epidermal Growth Factor Receptor
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung Cancer
Radiation Fields for lung cancer
2D technique
台北榮總肺癌團隊
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung Cancer
3D conformal technique
台北榮總肺癌團隊
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung Cancer
台北榮總肺癌團隊
 按2008年NCCN guideline的精神，其所建議的
放射治療已非傳統二次元定位的方式，而是因
應放射治療技術的進步，以電腦斷層評估腫瘤
的位置、體積和淋巴結引流的三次元定位方式，
來決定照射的角度、劑量和範圍。
 美國NCCN所建議的放射照射劑量並不完全適用
於國人，本共識以依國內病人狀況要做適度的
調整 。
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung Cancer
台北榮總肺癌團隊
Recommended Radiation Doses for NSCLC
(Modified doses for domestic patients)
Treatment Plan
Preoperative
Total Dose
Fraction Size
45-50 Gy
1.8 - 2 Gy
50 Gy
54-60 Gy
60-66 Gy
Up to 70 Gy
1.8 - 2 Gy
1.8 - 2 Gy
1.8 - 2 Gy
1.8 - 2 Gy
Postoperative
1.
2.
Negative margin
Extracapsular nodal extension
or microscopic positive margin
3. Gross residual tumor
Definitive
1. Without concurrent
chemotherapy
2.
Up to 70 Gy for volume< 25%
Up to 60-66 Gy for volume
between 25-36%
With concurrent chemotherapy Up to 60-66 Gy
(Mainly paclitaxel + carboplatin)
Palliative (for primary lung lesion;
SVC syndrome, obstructive
pneumonitis, etc.)
30-50Gy
1.8 - 2 Gy
1.8 - 2 Gy
1.8 - 2 Gy
2-2.5 Gy
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
台北榮總肺癌團隊
Lung Cancer
Dose Volume Data for Radiation Pneumonitis (Modified for domestic patients)
RT +/Induction Chemotherapy
Parameter
MLD
Concurrent Chemotherapy
Range
Pneumonitis
(%)
Range
Pneumonitis
(%)
< 10 (Gy)
10-20
21-30
> 30
0-10
9-16
24-27
24-44
< 16.5 (Gy)
≧16.5
11-13
36-45
≦ 42 (%)
> 42
3
38
< 20 (%)
21-25
26-30
>31
9
18
51
85
LP(5)
LP(20)
< 20 (%)
20-31
≧ 32
0-2 (%)
7-15
13-48
LP(30)
≦ 8 (%)
>8
6 (%)
24
MLD-Mean Lung Dose, LP: percentage of lung that received radiation (Gy)
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung Cancer
台北榮總肺癌團隊
同步化學併放射治療(CCRT)原則
◎ NSCLC Dose: up to 60-66Gy/1.8-2Gy/day
◎ Limited SCLC
1.年齡小於等於70歲，PS：0~1，接受CCRT DOSE：50~60 Gy/1.8Gy/day
排程：放療自開始持續做至50~60 Gy，而化學治療自開始先做三個療程後休
息，須重新評估病患治療反應，之後再依實際情形安排接續的治療。
如有CR 加做预防性全腦放射治療 (prophylactic cranial irradiation, PCI)
DOSE： 30Gy/ 2Gy/ day x15 fractions(一天一次共十五次）
如有PR 持續化學治療，但不做PCI
2.年齡大於70歲，PS：0~1，採用接續性化放療(sequential chemoradiotherapy)
DOSE：50~60 Gy/1.8Gy/day
排程：連續的三個療程的化學治療後休息，在二週內重新評估
如有CR 加做PCI, DOSE： 30Gy/ 2Gy/ day x15 fractions(一天一次共十五次）
如有PR 加做胸腔的放療及三個療程的化學治療，但不做PCI
3.如有PD 接受第二線化療。
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
台北榮總肺癌團隊
Lung Cancer
肺癌化學治療用藥準則 – 非小細胞肺癌
◎ 第一線
- Gemcitabine (GC-G)
G (1000-1250mg/m2) + Cisplatin (60-75mg/m2), Q3-4W.
（ 臨床試驗病例除外 ）
◎ 第二線
- Docetaxel
1. Docetaxel (60 - 75mg/m2)-D1, Q3W.
2. Docetaxel (30 - 35mg/m2)-D1,8, Q3W.
- Vinorelbine (NC-N)
Vinorelbine (25-30 mg/m2) + Cisplatin (60-75 mg/m2), Q3-4W.
※Oral Vinorelbine 劑量 = (IV Vinorelbine劑量) x 2.5
- Paclitaxel (TaC or TaC-Ta-Ta)
1. Paclitaxel (160-175 mg/m2)-D1 + Cisplatin (60- 75 mg/m2)-D1, Q3W.
2. Paclitaxel (60-80 mg/m2) -D1,8,15 + Cisplatin (60-75 mg/m2) -D1,
Q4W.
- Docetaxel (TC or TC-T)
1. Docetaxel (60-75 mg/m2)-D1 + Cisplatin (60-75 mg/m2)-D1, Q3W.
2. Docetaxel (30-35 mg/m2)-D1,8 + Cisplatin (60-75 mg/m2)- D1,Q3W.
※ 備註:
1. Elderly or poor performance status：cisplatin omited
2. Cisplatin 若改成 Carboplatin, 劑量為 (CCr+25) x AUC,
AUC = 4-6
3. Bevacizumab 7.5 mg/Kgw 可與 Gemcitabine/cisplatin或
paclitaxel/carboplatin可並用於第一線化學治療
- Alimta
1. Alimta (500mg/m2)-D1,Q3W.
◎ 第三線
- Iressa 250 mg, QD.
- Tarceva 150 mg, QD (self pay)
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
台北榮總肺癌團隊
Lung Cancer
肺癌化學治療用藥準則 – 小細胞肺癌
（ 臨床試驗病例除外 ）
◎ Standard regimens (PVP):
1. Cisplatin (60-75 mg/m2) + VP-16 (60-80 mg/m2) D1,2,3/ Q3W
2. Carboplatin (AUC=5)D1 + VP-16 (60-80 mg/m2) D1,2,3/ Q3W
◎ Relapsed regimens:
1. Ifosfamide 1000 mg/m2 D1-3 + oral VP16 50 mg D1-10/ Q3W
2. Topotecan 1.5 mg/m2 D1-3 + epirubicin 30 mg/m2 D1/ Q3W
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
台北榮總肺癌團隊
Lung Cancer
Chemotherapy Regimens for Adjuvant Therapy-Cisplatin base
Published Chemotherapy Regimens
Schedules
NC-N
Vinorelbine (25-30 mg/m2)-D1,8 + Cisplatin (60-75 mg/m2)-D1
Q3W for 4 cycles
GC-G
G (1000-1250mg/m2)-D1,8 + Cisplatin (60-75mg/m2)-D1
Q3W for 4 cycles
TC
Docetaxel (60-75 mg/m2)-D1 + Cisplatin (60-75 mg/m2)-D1
Q3W for 4 cycles
TC-T
Docetaxel (30-35 mg/m2)-D1,8 + Cisplatin (60-75 mg/m2)- D1
Q3W for 4 cycles
TaC
Paclitaxel (160-175 mg/m2)-D1 + Cisplatin (60- 75 mg/m2)-D1
Q3W for 4 cycles
TaC-Ta-Ta
Paclitaxel (100 mg/m2) -D1,8 + Cisplatin (60-75 mg/m2) -D1
Q3W for 4 cycles
Chemotherapy Regimens for Adjuvant Therapy- Alternative
Cisplatin 若改成 Carboplatin, 劑量為 (CCr+25) x AUC, AUC = 4-6
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
台北榮總肺癌團隊
Lung Cancer
Chemotherapy Regimens for Neoadjuvant Therapy
G-G-GC
Published Chemotherapy Regimens
Schedules
Gemcitabine 1000mg/m2 day 1, 8, 15; Cisplatin
90mg/m2 day 15
Q4W for 3 cycles
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung
Cancer Cancer
Primary
Tracheal
台北榮總肺癌團隊
Staging
Proposed TNM classification and staging for primary tracheal carcinoma*
*Ref: Paolo Macchiarini, Lancet Oncol 2006; 7: 83–91
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
WORKUP
CLINICAL
STAGE
ADDITIONAL EVALUATION
(as clinically indicated)
•Multidisciplinary
evaluation is encouraged
•PET/CT scan
•
•
•
H&P
CBC, platelet
Chemistry
profile
Smoking
cessation
counseling
PFT
Chest CT scan
Bronchoscopy
Brain MRI
•
•
•
•
•
Stage I-III,
IVA
Stage IVB
Metastatic
cancer
a
台北榮總肺癌團隊
Cancer
PrimaryLung
Tracheal
Cancer
•Consider 3D-CT
reconstruction (multi-planar
reconstruction, volume
rendering technique,
minimal intensity projector)
Medical fit for
a
surgery,
resectable
Medical unfit for
surgery,
or
b
unresectable,
or
surgery not
elected and
patient medically
able to tolerate
chemotherapy
Medical unfit for
surgery and
patient unable to
tolerate
chemotherapy
See Primary
Treatment
(TRACH-1 )
See Primary
Treatment
(TRACH-2 )
See Primary
Treatment
(TRACH-2 )
See Primary
Treatment
(TRACH-3)
Medically able to tolerate major thoracic surgery
Unresctable tumor: greater than 50% of tracheal length involved by tumor, “frozen”mediastinum, poor
general condition of patient, distant metastases in squamous cell carcinoma; Oncologist 1997;2;245-253
b
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung
Cancer Cancer
Primary
Tracheal
PRIMARY
TREATMENT
Medically fit for
surgery, a
resectable
a
c
Surgery
台北榮總肺癌團隊
ADJUNCTIVE/ADJUVANT
TREATMENT
Radiation
c
•Complete resection (R0):
50Gy over tumor bed and adjacent mediastinum
c
•Incomplete resection with residual margin
R1:
R2:
>60Gy over tumor bed and 50Gy over adjacent
mediastinum
Medically able to tolerate major thoracic surgery
R0=No cancer at resection margins, R1=Microscopic residual cancer, R2=Macroscopic residual cancer
TRACH-1
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung
Cancer Cancer
Primary
Tracheal
台北榮總肺癌團隊
PRIMARY TREATMENT
Medical unfit for
surgery,
or
b
unresectable,
or
surgery not elected
and patient
medically able to
tolerate
chemotherapy
Medical unfit
for surgery
and patient
unable to
tolerate
chemotherapy
RT, 60Gy + concurrent
chemotherapy (Cisplatinbased) (preferred)
or
Best supportive care
Best Supportive Care
•Obstruction: stent, laser,
photodynamic therapy, RT
(external 30-50Gy or brachytherapy)
•Pain control: RT and/or medications
•Nutrition
RT 60-66Gy
or
Best supportive care
b Unresctable
tumor: greater than 50% of tracheal length involved by tumor, “frozen”mediastinum, poor
general condition of patient, distant metastases in squamous cell carcinoma; Oncologist 1997;2;245-253
TRACH-2
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung
Cancer Cancer
Primary
Tracheal
台北榮總肺癌團隊
SALVAGE THERPAY
Karnofsky
performance
score > 60
or
ECOG
performance
score≦2
RT, 60Gy + concurrent
chemotherapy (Cisplatinbased) (preferred)
or
Chemotherapy
or
Best supportive care
Stage IVB
Metastatic cancer
Best Supportive Care
Karnofsky
performance
score ≦ 60
or
ECOG
performance
score≧3
Best supportive care
•Obstruction: stent, laser,
photodynamic therapy, RT
(external 30-50Gy or brachytherapy)
•Pain control: RT and/or medications
•Nutrition
TRACH-3
Taipei VGH Practice Guidelines:
Oncology Guidelines Index
Lung Cancer
本治療指引將每六個月檢討修訂一次
預定下次修訂日期: 97年9月
台北榮總肺癌團隊