Taipei VGH Practice Guidelines: Oncology Guidelines Index Lung Cancer 台北榮總肺癌診療共識 V.1.0 2011 台北榮總肺癌團隊 Revised on 2011/05/30 Released on 2011/05/31 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 台北榮總肺癌診療共識 • • • Multidisciplinary Team Taipei VGH Lung Cancer Panel Members TNM staging – Taipei VGH supplement to TNM staging – Table of stage grouping • Evaluation and treatment – – – – – – Stage o (Tis) Stage I (T1-2,N0) and Stage II (T1-2, N1) Stage IIB (T3,N0) and stage IIIA (T3,N1) Stage IIIA (T1-3,N3) and stage IIIB (T4, N0-1) Stage IIIB (T1-3,N3) Stage IIIB (T4,N2-3) (T4: pleural effusion or pericardial effusion) – Stage IV (M1: solitary site or disseminated) • • • • • • • Principles of Surgical Resection Principles of Pathology Principles of Radiation Therapy - Recommended Radiation Doses - Dose Volume Data for Radiation Pneumonitis • • Principles of CCRT Principles of Chemotherapy - Non-Small Cell Lung Cancer - Small Cell Lung Cancer • • • • Surveillance • Therapy for Recurrence and Metastases • Occult (Tx,N0,M0),Evaluation and Treatment Second Lung Primary, Evaluation, and Treatment Adjuvant Chemotherapy Neoadjuvant Chemotherapy Clinical Trials for Advanced/ Metastatic NSCLC Tracheal cancer References 關於此臨床指引:肺癌的診療仍在發展階 段,本指引主要在呈現目前肺癌診療的進 展與共識,醫師應鼓勵病患參與臨床試驗 ,使其有機會得到最好的治療。在本指引 中的化療用藥建議是基於現有的臨床證據, 和目前的衛生署或健保局規定無關。 Taipei VGH Practice Guidelines: Oncology Guidelines Index 台北榮總肺癌團隊 Lung Cancer 台北榮總肺癌委員會暨肺癌多專科團隊組織架構 癌委會 肺癌委員會暨肺癌多專科團隊 召集人:蔡俊明、許文虎 副召集人:賴信良、吳玉琮 個案管理師:宋易珍、洪秀瑩 非核心成員 核心成員 胸內 胸外 放射 病理 放療 核醫 藥劑部 骨科 營養 社工 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 李毓芹 蔡俊明 陳育民 邱昭華 胸外 許文虎 吳玉琮 放射 許明輝 吳美翰 陳俊谷 病理 周德盈 放療 顏上惠 陳一瑋 藍耿立 核醫 王世楨 林可瀚 胸腔 內科 賴信良 Taipei VGH Practice Guidelines: Oncology Guidelines Index Lung Cancer 台北榮總肺癌團隊 NSCLC &SCLC TNM Staging * MX has been removed by a general rule from UICC/AJCC. Taipei VGH Practice Guidelines: Oncology Guidelines Index Lung Cancer 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 Summary of Evaluation and Treatment • PFT: Necessary for all operable stages • PET (PET/CT) : recommend for all clinical stages, except – Wet IIIB or stage IV with disseminate M1 • Mediastinoscopy: recommend for all clinical stages, except – Peripheral T1N0 – Wet IIIB or stage IV with disseminate M1 p.s. N2 or N3 disease can be confirmed by other methods including mediastinotomy, thoracoscopy, EBUS-FNA, EUS-FNA, CT-guided-FNA, supraclavicle LN biopsy • Brain MRI: recommend for all clinical stages, except – Stage I – Wet IIIB or stage IV with disseminate M1 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.2.2009 Taipei VGH Practice Guidelines: Oncology Guidelines Index NSCL-2 Lung Cancer 台北榮總肺癌團隊 From NCCN guideline, V.2.2009 Taipei VGH Practice Guidelines: Oncology Guidelines Index NSCL-3 Lung Cancer 台北榮總肺癌團隊 From NCCN guideline, V.2.2009 Taipei VGH Practice Guidelines: Oncology Guidelines Index NSCL-4 Lung Cancer 台北榮總肺癌團隊 From NCCN guideline, V.2.2009 Taipei VGH Practice Guidelines: Oncology Guidelines Index NSCL-5 Lung Cancer 台北榮總肺癌團隊 From NCCN guideline, V.2.2009 Taipei VGH Practice Guidelines: Oncology Guidelines Index NSCL-6 Lung Cancer 台北榮總肺癌團隊 From NCCN guideline, V.2.2009 Taipei VGH Practice Guidelines: Oncology Guidelines Index NSCL-7 Lung Cancer 台北榮總肺癌團隊 From NCCN guideline, V.2.2009 Taipei VGH Practice Guidelines: Oncology Guidelines Index NSCL-8 Lung Cancer 台北榮總肺癌團隊 From NCCN guideline, V.2.2009 Taipei VGH Practice Guidelines: Oncology Guidelines Index NSCL-9 Lung Cancer 台北榮總肺癌團隊 From NCCN guideline, V.2.2009 Taipei VGH Practice Guidelines: Oncology Guidelines Index NSCL-10 Lung Cancer 台北榮總肺癌團隊 From NCCN guideline, V.2.2009 Taipei VGH Practice Guidelines: Oncology Guidelines Index 台北榮總肺癌團隊 Lung Cancer From NCCN guideline, V.2.2009 NSCL-11 Radiotherapy (2B) or or radiotherapy (2B) such as with surgery or radiotherapy Taipei VGH Practice Guidelines: Oncology Guidelines Index NSCL-12 Lung Cancer 台北榮總肺癌團隊 From NCCN guideline, V.2.2009 Taipei VGH Practice Guidelines: Oncology Guidelines Index 台北榮總肺癌團隊 Lung Cancer NSCL-13 EGFR-TKI regardless of PSb (category 2B) Therapy for recurrence and metastasis EGFR-TKI sensitive mutation (+)a EGFR mutation status known EGFR-TKI sensitive mutation (-) Stage IV PS= 0-1 Chemotherapy (category 1) or Bevacizumab + chemotherapy (if criteria met) PS= 2 Chemotherapy PS= 3-4 Best supportive care only (see NCCN palliative care guidelines) East Asian, never smoker & adnocarcinoma EGFR-TKI regardless of PSb (category 2B) EGFR mutation status unknown Others Switch to another EGFR-TKI (category 2B or 3) Progression after EGFR-TKI treatment a Tumors with EGFR gene deletion at exon 19 (747-750), mutation at L858R, L861Q and G719X are those usually sensitive to EGFR-TKI. is the preferred choice, but chemotherapy can be used if TKI is not available. b EGFR-TKI See NSCL-14 Taipei VGH Practice Guidelines: Oncology Guidelines Index NSCL-14 Lung Cancer 台北榮總肺癌團隊 From NCCN guideline, V.2.2009 Taipei VGH Practice Guidelines: Oncology Guidelines Index Lung Cancer 台北榮總肺癌團隊 From NCCN guideline, V.2.2009 NSCL-15 Or Gefitinib Or Gefitinib Gefitinib and Erlotinib in 2nd-line therapy : adenocarcinoma Gefitnib in 3rd-line therapy: adenocarcinoma; Erlotinib in 3rd-line therapy: NSCLC 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 • • • • 病理評估的目的包括: classify the lung cancer; determine the extent of invasion; establish the status of cancer involvement of surgical margins; determine the molecular abnormalities to predict for response to EGFR- TKI 。 手術病理報告應該有WHO肺癌組織分類。 Pure bronchioloalveolar carcinoma (BAC)應無stroma、pleura與 lymphatic spaces之侵犯。免疫染色: Non-mucinous BAC = TTF-1 (+) / CK7 (+) / CK20 (-); Mucinous BAC = TTF-1 (-) / CK7 (+) / CK20 (+) 。 免疫染色可幫助鑑別原發或轉移肺腺癌,區別腺癌及惡性間皮細胞 癌,決定腫瘤之神經內分泌分化。 EGFR: Epidermal Growth Factor Receptor TKI: Tyrosine Kinase Inhibitor 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腺癌很重要。大部分原發肺腺癌TTF-1為陽 性,轉移腺癌(甲狀腺癌除外)為陰性反應。 Primary lung adenocarcinoma: TTF-1(+) / CK7(+) / CK20(-) / CDX-2 (-) Metastatic colorectal carcinoma: TTF-1(-) / CK7(-) / CK20(+) / CDX-2 (+) EGFR mutation之有無與TKI治療之反應相關;如TKI 對exon21 mutation 與exon19 deletion之腫瘤治療效果良好。 K-ras與吸煙相關;K-ras與EGFR mutation為mutually exclusive;有Kras mutation對TKI治療效果不佳。 小細胞癌多數(95%)原發自肺,少數則來自肺外器官,二者有類似之臨 床和生物特性,極易廣泛轉移。小細胞癌細胞通常Keratin 及至少一種 之neuroendocrine differentiation markers (CD56, synaptophysin或 chromogranin A)呈陽性免疫染色。 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2009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. - Vinorelbine (NC-N) Vinorelbine (25-30 mg/m2 i.v. or 60-80 mg/m2 p.o.) + Cisplatin (60-75 mg/m2), Q3-4W. ◎ 第二線 - Docetaxel 1. Docetaxel (60 - 75mg/m2)-D1, Q3W. 2. Docetaxel (30 - 35mg/m2)-D1,8, Q3W. - Pemetrexed (500mg/m2)-D1,Q3W. - Paclitaxel (TaC or TaC-Ta-Ta) 1. Paclitaxel (160-175 mg/m2) + Cisplatin (60- 75 mg/m2), 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. - Pemetrexed (AC) Pemetrexed (500mg/m2) + Cisplatin (60-75mg/m2), Q3W. -Gefitinib 250 mg, QD. (if Adeno , EGFR sensitizing mutation(+) ) - Gefitinib 250 mg, QD. (if Adeno) - Erlotinib 150 mg, QD. (if Adeno) ◎ 第三線 - Erlotinib 150 mg, QD. (if NSCLC) ※ 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/kg 可與 chemotherapy 並用於第一線治療, 但限於non-squamous cell carcinoma, no hemoptysis, no untreated CNS mets 4. EGFR-TKI 可用於第一線治療, if EGFR-TKI sensitizing mutation(+) 5. Pemetrexate/cisplatin用於第一線治療以及 pemetrexate用於第二線 治療都僅限於non-squamous cell carcinoma * 病患若參加本院 IRB 同意 之臨床試驗,則依該臨床試驗 之治療計畫進行 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-platintinum based Published Chemotherapy Regimens Schedules Vinorelbine (25-30 mg/m2 i.v. or 60-80 mg/m2 p.o.)-D1,8 + Cisplatin (6075 mg/m2)-D1 Q3W for 4 cycles Other Acceptable Chemotherapy Regimens Schedules 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 TaC* Paclitaxel (160-175 mg/m2)-D1 + Cisplatin (60- 75 mg/m2)-D1 Q3W for 4 cycles NC-N Chemotherapy Regimens for Adjuvant Therapy-non platintinum based UFUR 300~400mg-QD (3 capsule QD) or 200mg BID (2 capsules BID) 2 years Chemotherapy Regimens for Adjuvant Therapy- Alternative Cisplatin 若改成 Carboplatin, 劑量為 (CCr+25) x AUC, AUC = 4-6 *Palitaxel+carboplatin regimen showed no survival benefit in stage IB patients 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 台北榮總肺癌診療共識 主要依據- 1.NCCN v3 2011 - 2.健保局最新給付標準 台北榮總肺癌團隊 Taipei VGH Practice Guidelines: Oncology Guidelines Index Lung Cancer 本治療指引將每年檢討修訂一次 預定下次修訂日期: 2012年05月 台北榮總肺癌團隊