Taipei VGH Practice Guidelines: Oncology Guidelines Index Lung Cancer 台北榮總肺癌團隊台北榮總肺癌診療共識台北榮總肺癌診療共識 V.2.0

台北榮總肺癌團隊Lung CancerTaipei VGH Practice Guidelines:

Oncology Guidelines Index

台北榮總肺癌診療共識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



台北榮總肺癌多專科團隊核心人員台北榮總肺癌多專科團隊核心人員

胸腔內科

陳育民賴信良

李毓芹蔡俊明彭瑞鹏

胸外吳玉琮許文虎

放射吳美翰許明輝

病理李永賢周德盈

放療陳一瑋顏上惠

邱昭華



NSCLC TNM Staging

Lababede, O. et al. Chest 1999;115:233-235



Clifton F. Mountain, CHEST1997

Regional Lymph Node Classification for Lung Cancer StagingRegional Lymph Node Classification for Lung Cancer Staging

- Extended mediastinoscopy- Mediastinotomy- VATS

- EUS-FNA- VATS

- EBUS-TBNA- VATS (limited to 10 and 11)

- Mediastinoscopy- EUS-FNA- EBUS-TBNA-VATS

- Mediastinoscopy; EUS-FNA, EBUS-TBNA

N1=Ipisilateral hilar nodes

N2=Subcarinal, ipisilateral mediastinal nodes

N3=Contralateral hilar/ mediastinal, or

supraclavicular or scalene nodes

How to Approach

EUS: Endoscopic Ultrasound; EBUS: Endobronchoscopic ultrasound; FNA: Fine Needle Aspiration; TBNA: Transbronchoscopic Needle Aspiration; VATS: Video Assisted Thoracoscopic Surgery



Summary of Evaluation and TreatmentSummary 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



Routine PET plus selective MediastinoscopyRoutine PET plus selective Mediastinoscopy- Stage I and II (T1-2 N0-1) lesion- Stage I and II (T1-2 N0-1) lesion

PET

Mediastinal nodes uptakeCentral located tumor or mediastinal nodes > 1cm

Surgical resection

Negative

and

Positive

or

Chest CT scan

Mediastinoscopynegative



Stage IIIA (T1-3, N2)Stage IIIB (T4, N0-1)



正子掃描（ PET/CT SCAN）：肺癌 clinical stage 的pre-treament 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）。



NSCL-1 From NCCN guideline, V.2.2008













































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 (Video- assisted thoracic surgery) 。



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 resection-sleeve lobectomy preferred over pneumonectomy) 。



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



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(K-ras with intrinsic resistance to TKI) 。

TKI: Tyrosine Kinase Inhibitor

EGFR: Epidermal Growth Factor Receptor



Radiation Fields for lung cancer

2D technique



3D conformal technique



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。



Recommended Radiation Doses for NSCLCRecommended Radiation Doses for NSCLC (Modified doses for domestic patients)(Modified doses for domestic patients)

Treatment Plan Total Dose Fraction Size

Preoperative 45-50 Gy 1.8 - 2 Gy

Postoperative1. Negative margin

2. Extracapsular nodal extension

or microscopic positive margin

3. Gross residual tumor

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

Definitive

1. Without concurrent chemotherapy

2. With concurrent chemotherapy

(Mainly paclitaxel + carboplatin)

Up to 70 Gy for volume< 25%

Up to 60-66 Gy for volume between 25-36%

Up to 60-66 Gy

1.8 - 2 Gy

1.8 - 2 Gy

1.8 - 2 Gy

Palliative (for primary lung lesion; SVC syndrome, obstructive pneumonitis, etc.)

30-50Gy 2-2.5 Gy



Dose Volume Data for Radiation Pneumonitis Dose Volume Data for Radiation Pneumonitis (Modified for domestic patients)(Modified for domestic patients)

RT +/-

Induction Chemotherapy

Concurrent Chemotherapy

Parameter Range Pneumonitis

(%)

Range Pneumonitis

(%)

MLD < 10 (Gy)

10-20

21-30

> 30

0-10

9-16

24-27

24-44

< 16.5 (Gy)

≧16.5

11-13

36-45

LP(5) ≦ 42 (%)

> 42

3

38

LP(20) < 20 (%)

20-31

≧ 32

0-2 (%)

7-15

13-48

< 20 (%)

21-25

26-30

>31

9

18

51

85

LP(30) ≦ 8 (%)

> 8

6 (%)

24

MLD-Mean Lung Dose, LP: percentage of lung that received radiation (Gy)



同步化學併放射治療 (CCRT)原則

◎ NSCLC Dose: up to 60-66Gy/1.8-2Gy/day

◎ Limited SCLC1.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。



– 肺癌化學治療用藥準則非小細胞肺癌（臨床試驗病例除外）

◎ 第一線 - Gemcitabine (GC-G) G (1000-1250mg/m2) + Cisplatin (60-75mg/m2), Q3-4W.

- 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

◎ 第二線 - Docetaxel 1. Docetaxel (60 - 75mg/m2)-D1, Q3W. 2. Docetaxel (30 - 35mg/m2)-D1,8, Q3W.

- Alimta 1. Alimta (500mg/m2)-D1,Q3W.

◎ 第三線 - Iressa 250 mg, QD.

- Tarceva 150 mg, QD (self pay)



– 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



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



Chemotherapy Regimens for Neoadjuvant Therapy

Published Chemotherapy Regimens Schedules

G-G-GC Gemcitabine 1000mg/m2 day 1, 8, 15; Cisplatin 90mg/m2 day 15

Q4W for 3 cycles



StagingProposed TNM classification and staging for primary tracheal carcinoma*

Primary Tracheal Cancer

*Ref: Paolo Macchiarini, Lancet Oncol 2006; 7: 83–91



• H&P• CBC, platelet• Chemistry

profile• Smoking

cessation counseling

• PFT• Chest CT scan• Bronchoscopy • Brain MRI

Stage I-III, IVA

Stage IVB

Metastatic cancer

•Multidisciplinary evaluation is encouraged

•PET/CT scan

•Consider 3D-CT reconstruction (multi-planar reconstruction, volume rendering technique, minimal intensity projector)

Medical fit for surgery, resectable

Medical unfit for surgery, or 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-3)

WORKUP CLINICAL STAGE

ADDITIONAL EVALUATION (as clinically indicated)

Primary Tracheal Cancer

a

a Medically able to tolerate major thoracic surgery 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

b


Oncology Guidelines Index Primary Tracheal Cancer

Medically fit for surgery, resectable

PRIMARY TREATMENT

Surgery

ADJUNCTIVE/ADJUVANT TREATMENT

Radiation •Complete resection (R0): 50Gy over tumor bed and adjacent mediastinum •Incomplete resection with residual margin R1: R2: >60Gy over tumor bed and 50Gy over adjacent mediastinum

a

a Medically able to tolerate major thoracic surgery c R0=No cancer at resection margins, R1=Microscopic residual cancer, R2=Macroscopic residual cancer

TRACH-1

c

c



Medical unfit for surgery, or 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 (Cisplatin-based) (preferred) or Best supportive care

RT 60-66Gy or Best supportive care

PRIMARY TREATMENT

Best Supportive Care

•Obstruction: stent, laser, photodynamic therapy, RT (external 30-50Gy or brachytherapy) •Pain control: RT and/or medications•Nutrition

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

b



Stage IVB

Metastatic cancer

Karnofsky performance score > 60 or ECOG performance score 2≦

Karnofsky performance score 60 ≦ or ECOG performance score 3≧

SALVAGE THERPAY

RT, 60Gy + concurrent chemotherapy (Cisplatin-based) (preferred) or Chemotherapy or Best supportive care

Best supportive care

Best Supportive Care

•Obstruction: stent, laser, photodynamic therapy, RT (external 30-50Gy or brachytherapy) •Pain control: RT and/or medications•Nutrition

TRACH-3



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

Documents

Taipei VGH Practice Guidelines: Oncology Guidelines Index Lung Cancer 台北榮總肺癌團隊 台 北 榮 總 肺 癌 診 療 共 識 台 北 榮 總 肺 癌 診 療 共 識 V.2.0

Taipei VGH Practice Guidelines: Oncology Guidelines Index Lung Cancer 台北榮總肺癌團隊台北榮總肺癌診療共識台北榮總肺癌診療共識 V.2.0