癌症診療準則與核心測量 : 肺癌 台中榮總胸腔內科陳焜結醫師 2009 年台灣地區主要癌症死亡原因 * 每十萬人口死亡率 癌症部位 人數 死亡率 * 肺癌 7951 34.5 肝癌 7759 33.6 結腸直腸癌 4531 19.4 乳癌 1588 13.9 胃癌 2282 9.9 口腔癌 2249 9.7 總計 39917 173.0
台灣肺癌的流行病學 No. 1 cause of cancer death in women No. 2 cause of cancer death in men Around 8000 death/yr due to lung cancer Highest rate of increase in cancer mortality M/F ratio around 2:1 High incidence of adenocarcinoma 肺癌危險因子 抽菸 二手菸 三手菸 空氣污染 : 石化燃料燃燒的產物等 氡 (Radon) 石棉 砷 Berryllium 鉻 鎳等 慢性肺病變如慢性發炎 COPD 肺纖維化 肺癌家族病史
國人肺癌之現況 肺癌就其生物特性和臨床表現分為小細胞肺癌和非小細胞肺癌兩大類, 後者主要包括腺癌 鱗狀細胞癌與大細胞癌三種類型 在臺灣, 前者約佔 12-15%, 後者共約 85-88% 小細胞肺癌生長快速, 很快就會發生擴散轉移, 但是它對化學及放射線治療相當敏感, 因此治療以全身性的化學藥物療法為主, 有八成以上的反應率 可惜的是經治療緩解後, 大多數病例在兩年內會復發, 復發後即對治療發生抗性 96 年癌症登記年報 - 肺癌
96 年肺症年齡別死亡率
早期肺癌篩檢 使用胸部 X 光及痰細胞學檢查不建議用於大規模早期肺癌篩檢 低劑量電腦斷層可用於高危險群族群篩檢找到早期肺癌, 但是否能降低肺癌的死亡率仍待驗證
肺癌的診斷 1). 病史詢問與理學檢查 2). 影像學檢查 a). 胸部 X 光片或超音波檢查 b). 胸部電腦斷層掃描 c). 核磁共振 d). 核子醫學掃描 e). 正子攝影 Symptoms at diagnosis of NSCLC Cough Dyspnea Weight loss Chest pain Hemoptysis Bone pain Fatigue Dysphagia Wheezing and stridor None (2-5%)
Presentation of Lung Cancer Frequency of Metastatic Involvement by Lung Cancer
肺癌的診斷 : 影像檢查 胸部 X 光 電腦斷層 (CT scan) 及核磁共振 (MRI) 胸部及腹部超音波 全身骨骼掃描 (Bone Scan) 正子攝影 (PEC scan or PET-CT scan) 其他
Chest Sonography
核子醫學掃描 正子攝影
PET SCAN 肺癌的診斷 : 病理診斷最重要 1. Sputum cytology or pleural effusion cytology 2. CT-guided or Sono-guided aspiration or biopsy 3. Bronchoscopy 4. Mediastinoscopy & Mediastinectomy 5. Lymph node biopsy or aspiration 6. Thoracoscopy 7. Open lung biopsy 8. Distant metastasis (skin, liver )
Sputum Cytology Chest Sonography
Chest Sonography CT guided Biopsy
LT VOCAL CORD PARALYSIS EBUS: Endobronchoscopic ultrasound
縱膈腔鏡 核心測量指標 : 診斷 (1) 有組織或細胞學診斷步驟的比例
Histological Types of Lung Cancer Relative Incidence
Gender Difference in Lung cancer Travis et al, J Clin Oncol 2005
Staging of Lung cancer Introduction- AJCC TNM for cancer staging developed by Pierre Denoix (1943-1952) In 1953, TNM for classification of cancer accepted by UICC In 1968, 1st edition of UICC staging manual TNM classification of Malignant tumor
Previous Staging system for lung cancer Small Dataset - The Mountain dataset In 1973, A Clinical Staging System for Lung cancer -- based on 2155 cases In 1986, A new International Staging System for lung cancer based on 3753 cases In 1997, Revisions in the International Staging System for lung cancer -- based on 5319 cases Surgically oriented Lack of validation Not International Advance technologies in clinical staging Past editions of the AJCC Cancer Staging Manual Edition 1 published 1977 and went into effect 1978 Edition 2 published 1983 and went into effect 1984 Edition 3 published 1988 and went into effect 1989 Edition 4 published 1992 and went into effect 1993 Edition 5 published 1997 and went into effect 1998 Edition 6 published 2002 and went into effect 2003
The 7th edition of TNM in Lung Cancer Tx T0 Primary tumour cannot be assessed, or malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy No evidence of primary tumor Tis Carcinoma in situ T1 T2 T1a T1b T2a T2b Tumour 3 cm, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus) Tumor 2 cm Tumor > 2cm - 3 cm 7cm Tumour >3 cm; or tumour with any of the following features: Involves main bronchus, 2 cm or more distal to the carina Invades visceral pleura Associated with atelectasis or obstructive pnemonitis that extends to the hilar region but does not involve the entire lung Tumor > 3cm - 5 cm Tumor > 5cm - 7 cm
Staging Manual in Thoracic oncology 2009 T3 T4 Tumour more than 7 cm or one that directly invades any of the following: chest wall (including superior sulcus tumours), diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium; or tumour in the main bronchus less than 2 cm distal to the carina1 but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung or separate tumour nodule(s) in the same lobe as the primary. Tumour of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, oesophagus, vertebral body, carina; separate tumour nodule(s) in a different ipsilateral lobe to that of the primary
Staging Manual in Thoracic oncology 2009 Staging Manual in Thoracic oncology 2009
N1 N2 N3 M1 Ipsilateral peribronchial, ipsilateral hilar Subcarinal, ipsilateral mediastinal Contralateral mediastinal or hilar, scalene or supraclavicular Distant metastasis M1a M1b Separate tumour nodule(s) in a contra-lateral lobe; pleural nodules or malignant pleural or pericardial effusion Distant metastasis J. Thorac. Oncol. 2009;4:568-577
Staging Manual in Thoracic oncology 2009 Staging Manual in Thoracic oncology 2009
Staging Manual in Thoracic oncology 2009 Invasion of visceral pleura (T2) is defined as invasion beyond the elastic layer including invasion to the visceral pleural surface. Tumour with direct invasion of an adjacent lobe, across the fissure or by direct extension at a point where the fissure is deficient, should be classified as T2a Staging manual in Thoracic oncology, 2009
Stage Grouping of Lung cancer N0 N1 N2 N3 T1a Ia IIa IIIa IIIb T1b Ia IIa IIIa IIIb T2a Ib IIa IIIa IIIb T2b IIa IIb IIIa IIIb T3 IIb IIIa IIIa IIIb T4 IIIa IIIa IIIb IIIb M1a or M1b IV Change in stage classification T and M descriptors N0 N1 N2 N3 6th Edition 7th Ed Stage Stage Stage Stage T1 (<=2cm) T1a IA IIA IIIA IIIB T1 (>2-3cm) T1b IA IIA IIIA IIIB T2 (>3, <=5cm) T2a IB IIB IIA IIIA IIIB T2 (>5-7cm) T2b IB IIA IIB IIIA IIIB T2 (>7cm) IB IIB IIB IIIA IIIA IIIB T3 invasion T3 IIB IIIA IIIA IIIB T4 (same lobe nodules) IIIB IIB IIIB IIIA IIIB IIIA IIIB T4 (extension) T4 IIIB IIIA IIIB IIIA IIIB IIIB M1 (ipslilateral lung) IV IIIA IV IIIA IV IIIB IV IIIB T4 (pleural effusion) M1a IIIB IV IIIB IV IIIB IV IIIB IV M1 (contralateral lung) IV IV IV IV M1 (distant) M1b IV IV IV IV
Staging of Small-cell Lung Cancer Limited disease (30-40%) Primary tumor confined to one hemithorax Ipsilateral hilar lymph nodes Ipsilateral and contralateral supraclavicular lymph nodes Ipsilateral and contralateral mediastinal lymph nodes Ipsilateral pleural effusion, independent of cytology Extensive disease (60-70%) Metastatic lesions in the contralateral lung Distant metastatic involvement (eg. brain, bone, liver) Treatment of Lung cancer Surgery Radiotherapy Chemotherapy Targeted therapy Combined therapy
Treatment of NSCLC Current Treatment of NSCLC Stage Primary Adjuvant Outcome treatment therapy IA Surgery 5 yr SR > 60-70% IB II C/T 5 yr SR > 40-50% IIIA (resectable) C/T+ Surgery Or Surgery+C/T C/T ±RT 5 yr SR > 15-30% IIIA (unresectable) IIIB (N3) CCRT or C/T R/T None 5 yr SR > 10-20% IV IV C/T (with targeted therapy); EGFR- TKI in selected population None Median survival: 10-12 Mo 1 yr SR, 40-50% 2 yr SR, 15-20%
Stage I-II NSCLC Surgical resection is standard of care Lobectomy is preferred Limited resection (segmentectomy or wedge resection) is an option for patients with compromised function. VATS is acceptable Intraoperative systematic mediastinal lymph node sampling or dissection for accurate pathologic staging SURGERY FOR LUNG CANCER Pneumonectomy Lobectomy Segmentectomy Lung-conserving procedures Sleeve lobectomy Bilobectomy
Sleeve RUL Lobectomy Lung Function Test before Operation of NSCLC FEV1 > 2 liters Pneumonectomy FEV1 < 2 liters Perfusion/Ventilation Scan If residual FEV1 > 0.8 liters Lobectomy If residual FEV1 around 0.8 liters Consider Segmentectomy If residual FEV1 < 0.8 liters Poor surgical candidates Exercise Pulmonary Function Test: May be indicated
VATS Benefits of VATS Fewer complication Less pain Better shoulder ROM Better PFT Better quality of life, earlier recovery Less pneumonia Easier for octogenarians Less cost Receive more adjuvant chemotherapy Less impact on immunotherapy Principles and Practice of lung cancer 4th ed.
Indications VATS lobectomy Clinical stage I lung cancer Tumor size <6cm Physiologic operability Contraindication Nodal disease densely adherent to vessels Chest wall or mediastinal invasion Neoadjuvant C/T and R/T Five-Year Survival Rates by Revised TNM Classification of NSCLC Stage TNM classification 5-year survival% Clinical Patholigical IA T1N0M0 61 67 IB T2N0M0 38 57 IIA T1N1M0 34 55 IIB T2N1M0,T3N0M0 24 39 IIIA T1-3N2M0, T3N1M0 13 23 IIIB T4AnyNM0, AnyTN3M0 5 NA IV Any TAnyNM1 1 NA
Adjuvant chemotherapy in Stage I- II patients Not recommended in stage IA NSCLC after completely resection Selective in Stage IB NSCLC after complete resection(e.g. tumor size >4cm) Recommended in Stage II NSCLC with good performance status after complete resection Platinum-based doublet Stage I-II patients Not candidates for surgery Curative radiotherapy is recommended
Adjuvant Radiotherapy in Stage I-II patients Not recommended for stage I patients with complete resection Decrease local recurrence but not survival benefit for stage II NSCLC, not recommended Lobectomy in Stage I patients had a higher 5-year survival rate ; Ann Thorac Surg 1995;60:615-622
; Ann Thorac Surg 1995;60:615-622 核心測量指標 診斷 (3) 手術治療的病人接受心肺功能檢查的比例 治療 (1) 病理第 I~II 期之非小細胞肺癌病患進行腫瘤完全切除性手術 ( 包含肺葉切除或肺切除 ) 的比例 治療 (2) 病理第 I~II 期之非小細胞肺癌病患接受肺楔狀或肺節切除的比例 治療 (3) 病理第 I- II 期之非小細胞肺癌病患完成組織淋巴結系統性取樣或摘除的比例
Treatment of Stage III NSCLC Multidisciplinary therapy (local +systemic) Concurrent or Sequential chemoradiotherpy Surgery with adjuvant chemotherapy/radiotherapy Neoadjuvant chemo(radio)therapy with Surgery Treatment of advanced or metastatic NSCLC Chemotherapy and targeted therapy provided survival benefit and better quality of life
1.5M HR: 0.73, p<0.0001 10% Survival in trials of supportive care versus supportive care plus chemotherapy (only trials using regimens based on cisplatin). BMJ 1995;311:899-909. JCO 2008;26:4617-4625
Classification of Chemotherapy Agents ALKYLATING AGENTS ANTI- METABOLITES MITOTIC INHIBITORS ANTIBIOTICS OTHERS BUSULFAN CYTOSINE ETOPOSIDE BLEOMYCIN L-ASPARAGINASE CARMUSTINE ARABINOSIDE TENIPOSIDE DACTINOMYCIN HYDROXYUREA CHLORAMBUCIL FLOXURIDINE VINBLASTINE DAUNORUBICIN PROCARBAZINE CISPLATIN FLUOROURACIL VINCRISTINE DOXORUBICIN TOPOTECAN CYCLOPHOSPHAMIDE MERCAPTOPURINE VINDESINE MITOMYCIN-C IRINOTECAN IFOSFAMIDE METHOTREXATE TAXOIDS MITOXANTRONE MELPHALAN GEMCITABINE VINORELBINE PLICAMYCIN ZD0473 PEMETREXED DISODIUM (ALIMTA) 常用於治療非小細胞肺癌的化學治療藥物 Cisplatin or Carboplatin Gemcitabine (Gemzar) Paclitaxel (Taxol) Docetaxel (Taxotere) Vinorelbine (Navelbine) Pemetrexed (Alimta) Irrinotecan Etoposide
Targeted therapy in Lung cancer Gefitinib: EGFR-TKI Erlotinib: EGFR-TKI Bevacizumab: Antiangiogenesis Cetuximab Treatment of SCLC Limited stage: Chemoradiotherapy is standard of care Cisplatin+Etoposide + Radiotherapy Extensive stage: Chemotherapy Cisplatin(or carboplatin)+etoposide Cisplatin+Irinotecan Prophylatic cranial irradiation
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