台北榮總肺癌診療共識 V.2.0 2008

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 胸腔內科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

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

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 Assisted Thoracoscopic Surgery Clifton F. Mountain, CHEST1997

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

or Positive negative Surgical resection Mediastinoscopy 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 Negative

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 NSCLC(Modified doses for domestic patients)

Dose Volume Data for Radiation Pneumonitis (Modified for domestic patients) MLD-Mean Lung Dose, LP: percentage of lung that received radiation (Gy)

◎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。同步化學併放射治療(CCRT)原則

◎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 – 非小細胞肺癌（臨床試驗病例除外）

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 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

Primary Tracheal Cancer Staging Proposed TNM classification and staging for primary tracheal carcinoma* *Ref: Paolo Macchiarini, Lancet Oncol 2006; 7: 83–91

Primary Tracheal Cancer WORKUP CLINICAL STAGE ADDITIONAL EVALUATION (as clinically indicated) Medical fit for surgery, resectable See Primary Treatment (TRACH-1 ) a Medical unfit for surgery, or unresectable, or surgery not elected and patient medically able to tolerate chemotherapy • Multidisciplinary evaluation is encouraged • PET/CT scan • Consider 3D-CT reconstruction (multi-planar reconstruction, volume rendering technique, minimal intensity projector) b See Primary Treatment (TRACH-2 ) • H&P • CBC, platelet • Chemistry profile • Smoking cessation counseling • PFT • Chest CT scan • Bronchoscopy • Brain MRI Stage I-III, IVA Medical unfit for surgery and patient unable to tolerate chemotherapy See Primary Treatment (TRACH-2 ) Stage IVB Metastatic cancer See Primary Treatment (TRACH-3) 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

Primary Tracheal Cancer PRIMARY TREATMENT ADJUNCTIVE/ADJUVANT TREATMENT Radiation c • 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 Medically fit for surgery, resectable c a Surgery 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

Primary Tracheal Cancer PRIMARY TREATMENT Medical unfit for surgery, or unresectable, or surgery not elected and patient medically able to tolerate chemotherapy RT, 60Gy + concurrent chemotherapy (Cisplatin-based) (preferred) or Best supportive care b • Best Supportive Care • Obstruction: stent, laser, photodynamic therapy, RT (external 30-50Gy or brachytherapy) • Pain control: RT and/or medications • Nutrition Medical unfit for surgery and patient unable to tolerate chemotherapy 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

Primary Tracheal Cancer SALVAGE THERPAY Karnofsky performance score > 60 or ECOG performance score≦2 RT, 60Gy + concurrent chemotherapy (Cisplatin-based) (preferred) or Chemotherapy or Best supportive care Stage IVB Metastatic cancer • Best Supportive Care • Obstruction: stent, laser, photodynamic therapy, RT (external 30-50Gy or brachytherapy) • Pain control: RT and/or medications • Nutrition Karnofsky performance score ≦ 60 or ECOG performance score≧3 Best supportive care 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

台北榮總肺癌診療共識 V.2.0 2008