高雄市立小港醫院 ( 委託財團法人高雄醫學大學經營 ) 105 年癌症診療指引目錄 診療指引修訂實證文獻參考來源 Page 1 Cancer of the Lung 肺癌 Non-Small-Cell Lung Cancer 非小細胞肺癌 Small-Cell Lung Cancer 小細胞肺癌 C

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1 105 年 癌症診療指引

2 高雄市立小港醫院 ( 委託財團法人高雄醫學大學經營 ) 105 年癌症診療指引目錄 診療指引修訂實證文獻參考來源 Page 1 Cancer of the Lung 肺癌 Non-Small-Cell Lung Cancer 非小細胞肺癌 Small-Cell Lung Cancer 小細胞肺癌 CCRT 的原則 Esophageal Cancer 食道癌 Hepato-biliary Pancreatic Cancer 肝膽胰癌 Hepatoma 肝癌 Cancer of the Gastrointestinal Tract 胃腸癌 Colon Cancer 結腸癌 Rectum Cancer 直腸癌 Gastric Cancer 胃癌 Cancer of the Breast 乳癌 Breast Cancer 乳癌 A A-1 A-22 A-28 A-29 B B-1 C C-1 C-14 C-22 D D-1

3 Gynecologic Cancer 婦癌 Cervical Cancer 子宮頸癌 Endometrial Cancer 子宮內膜癌 Cancer of the Head and Neck 頭頸癌 Cancer of the Oral Cavity 口腔癌 Urinary tract cancer 泌尿道癌 Bladder cancer 膀胱癌 Prostate cancer 前列腺癌 Lymphoma 淋巴癌 Diffuse large B-cell Lymphoma 瀰漫性大型 B 細胞淋巴癌 Follicular Lymphoma 濾泡型淋巴癌 E E-1 E-7 F F-1 G G-1 G-16 H H-1 H-3

4 診療指引修訂實證文獻參考來源 1. Breast Cancer NCCN V from 2. Non Hodgkins Lymphomas NCCN V from 3. Gastric Cancer NCCN V from 4. Bladder Cancer NCCN V from 5. Prostate Cancer NCCN V from 6. Cervical Cancer NCCN V from 7. Small Cell Lung Cancer NCCN V from 8. Non-Small Cell Lung Cancer NCCN V from 9. Colon Cancer NCCN V from Hepatobiliary Cancer NCCN V from Oral Cancer NCCN V from Esophagus Cancer V from 朱晟瑋 李書欣 陳榮祥 李金德 柯成國 郭功楷 (2007).Rectus Abdominis MyocutaneousFlap for a Large Epigastric Soft Tissue Defect Following Resection of a Needle TractImplanted Hepatocellular Carcinoma-A Case Report. 中華民國癌 症醫學會雜誌,23(4), 張文燦 李金德 (2010). 肝癌患者接受肝臟移植後復發之可能原因. 高雄醫師會誌 JOURNAL OF KAOHSIUNG MEDICAL ASSOCIATION,18(2), 國家衛生研究院肝癌小組專家共事會議結論報告 AASLD (American Association for the Study of Liver Diseases 美國肝病研究學會 ) practice guideline Hepatology NCCN Clinical Practice in Oncology: Hepatobiliary Cancers V Fukumoto T, Ku Y Induction chetherapy for hepatocellular carcinoma. In: Induction chemotherapy. (K.R.Aigner and F.O. Stephens eds.) Springer-Verlag Berlin Heidelberg. pp Sugimachi, K., Shirabe, K., Taketomi, A., Soejima, Y., Iguchi, T., Takeishi, K., Maehara, Y. (2011). Prognostic significance of preoperative imaging in recipients of living donor liver transplantation for hepatocellular carcinoma. [Comparative Study Evaluation Studies Research Support, Non-U.S. Gov't]. Transplantation,91(5), Efficacy of pegylated liposomal doxorubicin in patients with advanced hepatocellular carcinoma. PA,Lind. 2, s.l.:acta Oncol, 2007, Vol Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359: Arii S, Sata M, Sakamoto M, Shimada M, et al. Management of hepatocellular carcinoma: Report of Consensus Meeting in the 45th Annual Meeting of the Japan Society of Hepatology (2009). Hepatology Research, 2010, Vol.40,I 高雄醫學大學附設中和紀念醫院肝癌治療指引 7.0 版 發行日期 :2016 年 10 月發行版次 : 第 1 版編輯人員 : 侯明鋒 吳政毅 陳煌麒 李憲斌 林宜竑 莊捷翰 王秋麟 沈榮宗 張美玉 許經偉 謝佳蓉 黃柏堯 艾紀瑩 王亞婷 洪迪娜 黃惠娟 陳宜欣 蔡郁棻

5 Cancer of the Lung 肺癌 Treatment Guideline KMHK

6 肺癌修訂記錄 修訂日期 修訂內容摘要 修訂頁次 版本 第一版依照 NCCN guideline 制定本院治療準則多專科會議討論檢視未修改 多專科會議討論檢視未修改 多專科會議討論檢視未修改 *non-small cell lung cancer 修訂 non-small cell practice guideline 圖表中 initial A-1 evaluation 項目將原有的 CXR Abdominal sonography 刪除 2.stage I or II 的 treatment plan 改為 consult chest surgery to evaluate the indication for surgery ± chemotherapy or chemoradiation 3. 修訂 non-small cell clinical presentation, 將原本 N0-2 改為 N0-1, 並將 treatment plan 中 refer to KMUH 刪除, 原先 的 N3 or Metastatic disease 改為 N2 的 treatment plan A 修訂 small cell practice guideline 圖表中 initial evaluation 項目將原有的 CXR Abdominal sonography 刪除 *non-small cell lung cancer 1. 新增 surgical exploration and resection + mediastinal LN dissection or systematic LN sampling 後 stage IA 到 IIIA 的 margin positive 與 negative 的治療 A-3 A 修訂 stage IIIA 中 N2-metastatic 的 treatment A-3

7 肺癌修訂記錄 修訂日期修訂內容摘要修訂頁次版本 3. 新增 stage IIIB 治療流程之圖表 A-4 4. 修訂 NSCLC 中新增 stage IV,M1a 與 M1b 的 pretreatment evaluation 圖表 A-5 5. 新增 EGFR mutation 之治療流程 A-6 6.performance status 0-4 建議治療方式圖表 A-7 7. 新增 AJCC TNM 分期表 *small cell lung cancer 1. 新增 SCLC 中 limited stage 與 extensive stage 圖表說明 2. 新增 biopsy 之 pathology 結果後續的治療流程 A-8~A-9 A-10~A-11 A 新增 CCRT 原則 *non-small cell lung cancer 1. 新增 stage IIB stage IIIA 為 unresectable disease 治療流程 A-14 A-4~ A 新增 stage IIIA (N2 N3 nodes negative or N2 nodes positive) 治療流程 A-7 3. 新增 suspected multiple lung cancers 治療流程 A-8~9

8 肺癌修訂記錄 修訂日期修訂內容摘要修訂頁次版本 4. 新增 metastatic disease 在 adrenal 的治療流程 A-12 A 修訂 EGFR mutation positive 治療流程 A 新增 ALK positive 治療流程 A 新增 EGFR mutation and ALK negative or unknown 治療流 程 A 新增 squamous cell carcinoma first-line therapy 治療流程 A 新增 third-line therapy 治療流程 1. 修改 Sensitizing EGFR mutation positive,positive 可選這三個藥物 Erlotinib Afatinib Gefitinib 多專科會議討論檢視後未修改 A-19 A

9

10 Non-Small Cell Lung Cancer A-1 Pathologic Diagnosis of NSCLC Initial Evaluation Clinical Stage Stage IA peripheral (T1ab,N0) Medistinal CT negative (lymph nodes <1cm) See A-2 Stage I, peripheral (T2a,N0): central (T1ab-T2a,N0) Stage II (T1ab-T2ab,N1; T2b,N0): Stage IIB (T3,N0) Medistinal CT negative (lymph nodes <1cm) See A-2 Non-Small Cell Lung Cancer(NSCLC) *Pathology review *H & P(include performance status+ weight loss) *BW, BL, BSA *CT chest and upper abdomen, including adrenals *WBC, DC, Hgb, platelets *Chemistry profile *HbsAg, Anti-HCV *Smoking cessation advice, counseling, and pharmacotherapy *Integrate palliative care Stage IIB (T3 invasive,n0) Stage IIIA (T4 extension,,n0-1;t3,n1) Stage IIIA (T1-3,,N2) Separate pulmonary nodule(s) (Stage IIB, IIIA, IV) Stage IIIB (T1-3,N3): Medistinal CT positive Contralateral (lymph nodes 1cm) or Palpable superaclavicular lymph nodes Stage IIIB (T4 extension,,n2-3) on CT See A-4 See A-6 See A-6 Multiple lung cancers See A-8 See A-10 See A-11 Stage IV (M1a)(pleural or pericardial effusion) See A-11 Stage IV (M1b)(pleural or pericardial effusion) Solitary metastasis with resectable lung lesion See A-12 Stage IV (M1b) disseminated metastases See A-14

11 Non-Small Cell Lung Cancer A-2 Clinical Assessment Pretreatment Evaluation Stage IA (peripheral T1ab,N0) *PFTs (If not previously done) *Bronchoscopy (intraoperative preferred) *Pathologic mediastinal lymph node evaluation *Bone scan (refer to KMUH) *PET/CT scan (refer to KMUH) Negative mediastinal nodes Positive mediastinal nodes Operable Medically inoperable See initial treatment and adjuvant treatment(a-3) Definitive RT or stereotactic ablative radiotherapy (SABR) (refer to KMUH) See stage IIIA (A-7) or stage IIIAB(A-10) Stage IB(pheripheral T2a,N0) Stage I(central T1ab-T2a,N0) Stage II(T1ab-T2ab,N1;T2b,N0) Stage IIB(T3,N0) *PFTs (If not previously done) *Bronchoscopy (intraoperative preferred) *Bone scan(refer to KMUH) *Mediastinoscopy and/or EBUS/EUS(refer to KMUH) *PET/CT scan(refer to KMUH) Negative mediastinal nodes Positive mediastinal nodes Operable Medically inoperable See initial treatment and adjuvant treatment(a-3) N0 N1 Definitive RT including SABR Definitive chemoradiation See stage IIIA (A-7) or stage IIIAB(A-10) Adjuvant C/T for high risk stages IB-II *Brain MRI (stage II, stage IB)

12 Non-Small Cell Lung Cancer A-3 Initial treatment Findings at surgery Adjuvant treatment Stage IA (T1ab,N0) Margins negative (R0) Margins positive (R1, R2) Observe Reresection (preferred) or RT Surgical exploration and resection + Stage IB (T2a,N0) Stage IIA (T2b,N0) Margins negative (R0) Margins positive (R1, R2) Observe or Chemotherapy for high risk patients Reresection (preferred) ±chemotherapy or RT ±chemotherapy (chemotherapy for stage IIA) mediastinal lymph node diseeection or systematic lymph node sampling Stage IIA (T1ab-T2a,N1) Stage IIB (T3,N0;T2b,N1) Margins negative (R0) Margins positive R1 Chemotherapy Reresection + chemotherapy or chemoradiation R2 Reresection + chemotherapy or Concurrent chemoradiation Stage IIIA (T1-3,N2;T3,N1) Margins negative (R0) Margins positive R1 Chemotherapy + RT or Sequential chemotherapy+rt (N2 only) Chemoradiation (sequential or concurrent) R2 Concurrent chemoradiation

13 Non-Small Cell Lung Cancer A-4 Clinical Assessment Pretreatment Evaluation Clinical Evaluation Stage IIB (T3 invasion, N0) Stage IIIA (T4 extension, N0-1; T3, N1) *PFTs (If not previously done) *Bronchoscopy * Pathologic mediastinal lymph node evaluation *Brain MRI *Bone scan(refer to KMUH) *MRI of spine + thoracic inlet for superior sulcus lesions abuttling the spine or subclavian vessels (option) *PET/CT scan (refer to KMUH) Superior sulcus tumor See A-5 Chest wall See A-5 Proximal airway or See A-5 mediastinum Unresectable disease See A-5 Metastatic disease See A-12 or A-13

14 Non-Small Cell Lung Cancer A-5 Clinical Presentation Initial treatment Adjuvant Treatment Superior suicus tumor (T3 invasion, N0-1) Preoperative concurrent chemoradiation Surgery+ chemotherapy Superior suicus tumor (T4 extension, N0-1) Possibly resectable Unresectable Preoperative concurrent chemoradiation Definitive concurrent Surgical reevaluation Resectable Unresectable Surgery+ chemotherapy Complete definitive RT + chemotherapy See A-13 chemoradiation Chest wall, proximal airway or mediastinum (T3 invasion, N0-1; Resectable T4 extension, N0-1) Concurrent chemoradiation or Chemorherapy Surgery Margins negative (R0) Margins positive(r1,r2) R1 R2 Chemotherapy Reresection+ chemotherapy or chemoradiation (sequential or concurrent) Reresection+ chemotherapy or Concurrent chemoradiation Stage III (T4, N0-1) Unresectable Definitive concurrent chemoradiation

15 Non-Small Cell Lung Cancer A-6 Clinical Assessment Pretreatment Evaluation Mediastinal Biopsy Findings and Resectability *PFTs (If not previously done) N2, N3 nodes negative See A-7 Stage IIIA (T1-3, N2) *Bronchoscopy * Pathologic mediastinal lymph node evaluation N2 nodes positive See A-7 *Bone scan(refer to KMUH) *PET/CT scan (refer to KMUH) N3 nodes positive See A-10 *Brain MRI Metastatic disease See A-12 or A-13 Separate pulmonary nodule(s) (Stage IIB, IIIA,IV) *PFTs (If not previously done) *Bronchoscopy * Mediastinoscopy(option) *Bone scan(refer to KMUH) *Brain MRI Separate pulmonary nodule(s), same lobe (T3, N0) or ipsilateral non-primary lobe (T4,N0) Stage IV (N0, M1a): Contralateral lung (solitary nodule) See A-8 See A-8 *PET/CT scan (refer to KMUH) Extrathoracic metastatic disease See A-12or A-13

16 Non-Small Cell Lung Cancer A-7 Mediastinal Biopsy Findings T1-3, N0-1 (including T3 with multiple nodules in same lobe Surgery Resectable Medically inoperable Initial Treatment Surgical resection + mediastinal lymph node dissection or systematic lymph node sampling See A-2 N0-1 N2 Adjuvant Treatment See A-3 Margins negative Margins positive Sequential chemotherapy + RT See A-13 R1 R2 Chemoradiation (sequential or concurrent) Concurrent chemoradiation See A-13 See A-13 T1-2, T3( 7cm), N2 nodes positive *Brain MRI *PET/CT(refer to KMUH) Negative for M1 disease Definitive concurrent chemoradiation or induction chemotherapy No apparent progression Progression Surgery±chemotherapy±RT Local RT±chemotherapy Systemic See A-12 or A-13 Positive See A-12 or A-13 T3(invasion), N2 nodes positive *Brain MRI *PET/CT(refer to KMUH) Negative for M1 disease Positive Definitive concurrent chemoradiation See A-12 or A-13

17 Non-Small Cell Lung Cancer A-8 Clinical Presentation Initial Treatment Adjuvant Treatment Separate pulmonary nodule(s), same lobe (T3, N0) or ipsilateral nonprimary lobe (T4, N0) Surgery Margin negative (R0) Margins positive (R1,R2) Chemotherapy Concurrent chemoradiation (if tolerated) See A-13 See A-13 Stage IV ( N0, M1a) Contralateral lung (solitary nodule) Treat as two primary lung tumors if both curable See A-1 Suspected multiple lung cancers (based on the presence of biopsy-proven synchronous lesions or history of lung cancer *chest CT with contrast *PET/CT(refer to KMUH) *Brain MRI Disease outside of chest No disease outside of chest See A-14 Pathological mediastinal lymph node evaluation N2-3 N0-1 See A-14 See A-9

18 Non-Small Cell Lung Cancer A-9 Clinical Presentation Initial Treatment Low risk of becoming symptomatic Observation See A-13 Multiple Asymptomatic lesions High risk of becoming symptomatic Definitive local therapy Parenchymal sparing resection (preferred) or Solitary lesion possible radiation or ablation Multiple lung cancers (metachronous disease Definitive local therapy Consider palliative chemotherapy ± local not possible palliative therapy Symptomatic See A-14

19 Non-Small Cell Lung Cancer A-10 Clinical Assessment Pretreatment Evaluation Initial Treatment *PFTs (If not previously done) *PET/CT scan (refer to KMUH) *Brain MRI N3 negative See A-7 *Bone scan(refer to KMUH) * Pathologic confirmation of N3 disease by either: Stage IIIB (T1-3, N3) -Mediastinoscopy -Superaclavicular lymph node biopsy -Thoracoscopy N3 positive Definitive concurrent chemoradiation - Needle biopsy - Mediastinotomy - Endoscopic ultrasound (EUS) biopsy(refer to KMUH) Metastatic disease See A-12 or A-13 - Endobronchial ultrasound (EBUS) biopsy(refer to KMUH)

20 Non-Small Cell Lung Cancer A-11 Clinical Assessment Pretreatment Evaluation Initial Treatment Ipsilateral mediastinal node See A-7 Contralateral negative (T4, N0-1) *PET/CT scan(refer to KMUH) mediastinal Stage IIIB (T4 extension, N2-3) *Brain MRI *Bone scan (refer to KMUH) * Pathologic confirmation of N2-3 disease by either: -Mediastinoscopy -Superaclavicular lymph node biopsy -Thoracoscopy - Needle biopsy node negative Contralateral mediastinal node positive (T4, N3) Ipsilateral mediastinal node positive (T4, N2) Definitive concurrent chemoradiation Definitive concurrent chemoradiation - Mediastinotomy - EUS biopsy (refer to KMUH) - EBUS biopsy (refer to KMUH) Metastatic disease See A-12 or A-13 Stage IV, M1a: Thoracenfesis or pericardiocentesis ± Negative See A-7 Pleural or pericardial effusion thoracoscopy if thoracentesis indeterminate Positive Local therapy if necessary (e.g. pleurodesis, ambulatory small catheter drainage, pericardial window) + See A-12 or A-13

21 Non-Small Cell Lung Cancer A-12 Clinical Assessment Pretreatment Evaluation Initial Treatment Surgical resection of lung lesion Chemotherapy or Surgical resection followed by whole brain RT (WBRT) or T1-2, N0-1; T3, N0; Stereotactic ablative radiotherapy (SABR) of lung lesion Surgical stereotactic radiosurgery (SRS) or resection of Stage IV, M1b: Solitary site *Pathologic mediastinal lymph node evaluation *Bronchoscopy *Brain MRI *Bone scan(refer Brain or SRS + WBRT (category 1 for one metastasis) or SRS alone T1-2, N2; T3, N1-2; Any T, N3; T4, Any N Chemotherapy See A-14 lung lesion or SABR of lung lesion to KMUH) *PET/CT scan (refer to KMUH) Adrenal Pathologic diagnosis by needle or resection Local therapy for adrenal lesion (if lung lesion curable, based on T and N stage) or see A-14

22 Non-Small Cell Lung Cancer Therapy for recurrence and metastasis A-13 Surveillance Endobronchial obstruction *Laser/stent/other surgery * External-beam RT or brachytherapy *Photodynamic therapy No evidence of clinical/radiographic disease (NED), stage I-IV. *History and physical and chest CT ± contrast every 6-12 mo for 2 y Locoregional recurrence Resectable recurrence Mediadtinal lymph node recurrence Superior vena cava (SVC) obstruction *Reresection (preferred) * External-beam RT or SABR No prior RT Prior RT Concurrent chemoradiation Systemic chemotherapy * Concurrent chemoradiation (if not previously given) *External-beam RT * SVC stent No evidence of disseminated disease Evidence of disseminated disease Observation or systemic chemorherapy See A-14 (category 2B), then H&P and a non-contrast- enchanced chest CT annually (category 2B) *Smoking cessation advice, Severe hemoptysis *External-beam RT or brachytherapy * Laser or photodynamic therapy or Embolization *Surgery counseling and pharmacotherapy *PET or brain MRI is not indicated Localized symptom Palliative external-beam RT for routine follow-up. Diffuse brain metastases Palliative external-beam RT See A-14 Distant metastases Bone metastasis Solitary metastasis * Palliative external-beam RT + orthopedic stabilization, if risk of fracture *Consider bisphosphonate therapy or denosumab See A-12 Disseminated metastases See A-14

23 Non-Small Cell Lung Cancer A-14 Systemic Therapy for Metastatic Disease Evaluation Metastatic disease *Establish histologic subtype with adequate tissue for molecular testing (consider rebiopsy if appropriate) *Smoking cessation advice, counseling *Intergrate palliative care Histologic Subtype *Adenocarcinoma *Large cell *NSCLC not otherwise specified (NOS) Squamous cell carcinoma *EGFR mutation testing *ALK testing * EGFR± ALK testing should be conducted as part of multiplex/next-generation sequencing Sensitizing EGFR mutation positive ALK positive *Consider EGFR mutation and ALK testing especially in nerver smokers or small biopsy, specimens, or mixed histology *EGFR± ALK testing should be conducted as part of multiplex/next-generation sequencing Sensitizing EGFR mutation and ALK negative or unknown See A-18 See A-15 See A-16 See A-17

24 Non-Small Cell Lung Cancer A-15 Adenocarcinoma, large cell, NSCLC NOS: sensitizing EFGR mutation positive First-line therapy Second-line therapy brain Isolated lesion Consider local therapy and continue erlotinib or afatinib or Gefitinib EGFR Multiple lesions Consider WBRT and continue erlotinib or afatinib or Gefitinib Sensitizing EGFR mutation positive mutation discovered prior to first-line chemotherapy EGFR mutation discovered during first-line chemotherapy Erlotinib or Afatinib or Gefitinib Interrupt or complete planned chemotherapy, start erlotinib or afatinib or Gefitinib or May add erlotinib or afatinib to Progre- ssion Symptomatic Asymptomatic systemic Isolated lesion Multiple lesions Continue erlotinib or afatinib or Gefitinib Consider local therapy and continue erlotinib or afatinib or Gefitinib Consider platinum double ± bevacizumab ± erlotinib Progre- ssion See A-19 current chemotherapy

25 Non-Small Cell Lung Cancer A-16 Adenocarcinoma, large cell, NSCLC NOS: ALK positive First-line therapy Second-line therapy Isolated lesion Consider local therapy and continue crizotinib brain ALK Multiple lesions Consider WBRT and continue crizotinib Sensitizing EGFR mutation positive rearrangement discovered prior to first-line chemotherapy ALK Crizotinib Progre- ssion Symptomatic systemic Isolated lesion Multiple lesions Consider local therapy and continue crizotinib Consider platinum double ± bevacizumab Progre- ssion See A-19 rearrangement discovered during first-line chemotherapy Interrupt or complete planned chemotherapy, start crizotinib Asymptomatic Continue crizotinib

26 Non-Small Cell Lung Cancer Adenocarcinoma, large cell, NSCLC NOS: EGFR mutation and ALK negative or unknown A-17 First-line Therapy Second-line Therapy PS 0-1 Doublet chemotherapy or Bevacizumab+ chemotherapy or Progression PS 0-2 If not already given: Docetaxel or Pemetrexed or Erlotinib or Gemcitabine See A-19 Erlotinib or Cetuximab/vinorelbine / cisplatin Tumor response evaluation PS 3-4 Best supportive care Progression See second-line therapy, above PS 2 PS 3-4 Chemotherapy Best supportive care Reaponse or stable disease 4-6 cycles (total) Tumor response evaluation Reaponse or stable disease Continuation maintenance *bevacizumab *cetuximab *pemetrexed *bevacizumab+ pemetrexed *gemcitavine or *Switch maintenance * pemetrexed or erlotinib or Close observation Progression, see secondline therapy, above

27 Non-Small Cell Lung Cancer A-18 Squamous cell carccinoma First-line Therapy Second-line Therapy 斯 If not already given: PS 0-1 Doublet chemotherapy or Cetuximab/vinorelbine / cisplatin Tumor response evaluation Progression PS 0-2 PS 3-4 Docetaxel or Erlotinib or Gemcitabine Best supportive care Progression See A-19 See second-line therapy, above Response 4-6 Tumor PS 2 PS 3-4 Chemotherapy Best supportive care or stable disease cycles (total) response evaluation Response or stable disease Continuation maintenance *cetuximab *gemcitavine or Switch maintenance or Close observation Progression, see secondline therapy, above

28 Non-Small Cell Lung Cancer A-19 Adenocarcinoma, large cell, NSCLC NOS, or Squamous cell carccinoma Third-line Therapy PS 0-2 If not already given: Docetaxel or Pemetrexed( non-squamous) or Progression PS 0-2 Best supportive care or Clinical trial Erlotinib or PS 3-4 Best supportive care Progression Gemcitabine Erlotinib PS 3-4 or Best supportive care

29 A-20 分期 TX T0 Tis T1 T1a T1b T2 T2a T2b T3 T4 NX N0 Primary Tumor (T) Primary tumor cannot be assessed No evidence of primary tumor The Carcinoma in situ Tumor 3 cm in greatest dimension, 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 is 2 cm in greatest dimension Tumor > 2 cm but 3 cm in greatest dimension Tumor >3 cm but 7cm or tumor with any of the following features ( T2 tumors with these features are classified T2a if 5cm) Involves main bronchus, 2 cm distal to the carina Invades visceral pleura(pl1 or PL2) Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung Tumor > 3 cm but 5 cm in greatest dimension Tumor > 5 cm but 7 cm in greatest dimension Tumor >7cm or one that directly invades any of the following: parietal pleural(pl3) chest wall (including superior sulcus tumors), diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium; or tumor in the main bronchus( < 2 cm distal to the carina*, but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung or separate tumor nodule(s) in the same lobe Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina; or separate tumor nodule(s) in a different ipsilateral lobe * The uncommon superficial tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to main bronchus, is also classified as T1a. Regional Lymph Nodes (N) Regional lymph nodes cannot be assessed No regional lymph node metastasis

30 N1 N2 N3 M0 M1 M1a M1b Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and intrapulmonary nodes including involvement by direct extension Metastasis in ipsilateral mediastinal and/or subcarinal lymph nodes(s) Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph nodes(s) Distant Metastasis (M) No distant metastasis (no pathologic M0; use clinical M to complete stage group) Distant metastasis Separate tumour nodule(s) in a contralateral lobe; Tumour with pleural nodules or malignant pleural( or pericardial) effusion. Distant Metastasis** ** Most pleural (and pericardial) effusions with lung cancer are due to tumor. In a few patients, however, multiple cytopathologic examinations of pleural (pericardial) fluid are negative for tumor, and the fluid is nonbloody and is not an exudate. Where these elements and clinical judgement dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging element and the patient should be classified as M0. A-21 T1a T1b T2a T2b T3 T4 N0 IA IB IIA IIB IIIA N1 IIA IIA IIB IIIA IIIA N2 IIIA IIIA IIIA IIIA N3 IIIB IIIB IIIB IIIB 1.J Thorac Oncol. 2007, 2: Staging Manual in Thoracic Oncology, IASLC, AJCC, 7 th edition.

31 Small Cell Lung Cancer A-22 Diagnosis Initial Evaluation Stage Small cell or combined small cell/non-small cell lung cancer on biopsy or cytology of primary or metastatic site *H & P *Pathology review * WBC, DC, Hgb, platelets *Electrolytes, liver function *BUN, creatinine *Chest/liver/adrenal CT with IV contrast whenever possible *Head MRI (preferred) or CT *Bone scan (refer to KMUH) Limited stage (T any, N any, M0; except T3-4 due to multiple lung nodules that do not fit in a tolerance radiation on field) See A-23 *PET/CT scan (if limited stage is suspected) (option) *Smoking cessation counseling and intervention Extensive stage (T any, N any, M1a/b; T3-4 due to multiple lung nodules) See A-25

32 Small Cell Lung Cancer A-23 Stage Additional Workup *If pleural effusion is present, Clinical stage (T1-2, N0) PET/CT (if not previous obtained) Pathologic mediastinal staging is considered See A-24 thoracentesis is recommended; if Limited stage (T any, N any, M0; except T3-4 due to multiple lung nodules that do not fit in a tolerable radiation field) thoracentesis inconclusive, consider thoracoscopy *Pulmonary function tests (PFTs) (if clinically indicated) *Bone imaging(radiographs or MRI) as appropriate if PET-CT equivocal *Unilateral marrow aspiration/biopsy in select patients Limited stage in excess of T1-2, N0 Bone marrow biopsy, thoracentesis, or bone studies See A-24 See A-25 consistent with malignancy

33 Small Cell Lung Cancer A-24 Testing Results Initial Treatment Adjuvant Treatment Pathologic mediastinal staging negative Lobectomy (preferred) and mediastinal lymph node dissection or sampling N0 N+ Chemotherapy Concurrent chemotherapy + Clinical stage T1-2, N0 Pathologic Good performance status (PS 0-2) mediastinal RT Chemotherapy + concurrent thoracic RT See A-26 mediastinal staging positive or medically inoperable Poor PS (3-4) due to SCLC Chemotherapy ± RT Poor PS (3-4) not Individualized treatment due to SCLC including supportive care Good performance Chemotherapy + concurrent status (PS 0-2) thoracic RT See A-26 Limited stage excess T1-2, N0 Poor PS (3-4) due to SCLC Chemotherapy ±RT Poor PS (3-4) not Individualized treatment due to SCLC including supportive care

34 Small Cell Lung Cancer A-25 Stage Initial Treatment Extensive stage without localized *Good PS (0-2) *Poor PS (3-4) due to SCLC Combination chemotherapy including supportive care See NCCN Palliative Care Guidelines symptomatic sites or brain metastases *Poor PS (3-4) not due to SCLC Individualized therapy including supportive care See NCCN Palliative Care Guidelines Extensive stage (T any, N any, M1a/b; T3-4 due to multiple lung nodules) Extensive stage + localized symptomatic sites *SVC syndrome *Lobar obstruction *Bone metastases Spinal cord compression Chemotherapy± RT to symptomatic sites If high risk of fracture due to osseous structural impairment, consider palliative external-beam RT and orthopedic stabilization RT to symptomatic sites before chemotherapy unless immediate systemic therapy is required. See A-26 Extensive stage with Asymptomatic May administer chemotherapy first, with whole-brain RT after chemotherapy brain metastases Symptomatic Whole-brain RT before chemotherapy, unless immediate systemic therapy is required

35 Small Cell Lung Cancer A-26 Response Assessment Following Initial Therapy Adjuvant Treatment Surveillance After recovery from primary therapy: *Oncology follow-up visits every 3-4 *Chest x-ray (optional) *Chest/liver/adrenal CT with IV contrast whenever possible *Brain MRI (preferred) or CT with IV contrast whenever possible, if prophylactic cranical irradiation (PCI) to be given *Other image studies, to assess prior sites of involvement, as clinically indicated Complete response or partial response Stable disease Limited or extensive stage: PCI mo during y 1-2, at least every 6 mo during y 3-5, then annually -At every visit: H&P, chest imaging, bloodwork as clinically indicated *New pulmonary nodule should initiate workup for potential new primary *Smoking cessation intervention *PET/CT is not recommended for routine follow-up See A-27 *CBC, platelets *Electrolytic, LFTs, Ca, BUN, creatinine Primary progressive disease See A-22

36 Small Cell Lung Cancer A-27 Progressive Disease Subsequent Therapy/Palliative Therapy PS 0-2 Subsequent chemotherapy (category 1 for topotecan) or palliative symptom management, Continue until two cycles beyond best response or progression of disease or development of unacceptable toxicity Palliative symptom management, including localized RT to symptomatic sites including localized RT to Relapse or primary symptomatic sites progressive disease PS 3-4 Palliative symptom management, including localized RT to symptomatic sites

37 A-28 NSCLC Dose: up to 60-66Gy/1.8-2Gy/day CCRT 的原則 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 Principles of chemotherapy regimen 1.Chemotherapy at systemic doses results in superior outcome but at the cost of an increased toxicity. 2.Platinum-based regimen is preferred 3.Reference regimens with combination of platinum Etoposide Vinorelbine or Vinblastine 4.Alternative regimens with combination of platinum Paclitaxel Docetaxel

38 Pemetrexed 5.High-risk drugs for CCRT Gemcitabine EGFR-TKI (gefitinib, erlotinib) Bevacizumab Doxorubicin A-29

39 Cancer of the Liver Treatment Guideline KMHK

40 肝癌修訂記錄 修訂日期修訂內容摘要修訂頁次版本 97 年 98 年 99 年 100 年 101 年 102 年 肝癌診療指引新制訂 多科會議討論檢視後未修改 多科會議討論檢視後未修改 多科會議討論檢視後未修改 多科會議討論檢視後未修改 診療指引 1. 原甲種胎兒蛋白 400ng/ml, 無其他癌症, 且無急性肝炎 發作或懷孕 修改為甲種胎兒蛋 400ng/ml, 腫瘤 >1cm, 無其他癌症, 且無急性肝炎發作或懷孕 2. 原甲種胎兒蛋白 :>400ng/ml, 但同時有其他癌症或急性發作 <400ng/ml, 影像學無法分辨良惡性 修改為甲種胎兒蛋白 : 400ng/ml, 腫瘤 1cm, 但同時有其他癌症或急性肝炎發作 <400ng/ml, 影像學無法分辨良惡性 3. 原有影像學或臨床資料足以診斷 修改為腫瘤 >1cm 有影像學或臨床資料足以診斷 肝癌治療前評估項目建議檢查清單 1. 病因 Option: 刪除 Anti-HDV 2. 肝癌標記刪除 Alk-p r-gt TPA 3. 肝癌分級影像學檢查 : 原腹部超音波, 有腹部電腦斷層 掃瞄或磁振掃瞄 ( 在開始治療之前 ), 血管攝影 ( 可與 治療同時安排 ) 等評估腫瘤大小 腫瘤侵犯 及腹部 淋巴節轉移之檢查 修改為腹部超音波, 有顯影之腹 部電腦斷層掃瞄或磁振掃瞄 ( 在開始治療之前 ), 血管 攝影 ( 可與治療同時安排 ) 等評估腫瘤大小 腫瘤侵 犯 及腹部淋巴節轉移之檢查 B-1 B

41 肝癌修訂記錄 修訂日期修訂內容摘要修訂頁次版本 103 年 104 年 肝癌各種治療法適應症指引 1. 手術切除符合條件新增主治醫師認為手術對病患病情控 制較有利時, 仍可與病人討論後採用手術治療 2. 局部消除治療 : 經皮藥物注射治療 (PEI): 大型肝癌一般不建議, 但可施行血管內肝癌注射者或特殊情況時亦可嘗試, 請會診肝癌團隊會議 修改為大型肝癌一般不建議, 但可施行血管內肝癌注射者或特殊情況時亦可嘗試, 可與其他治療併用為輔助治療 3. 新增微波凝固治療 (micro-wave) 治療 修訂肝癌治療流程圖如附件 新增分期 : 1.HCC Staging :BCLC 新增 TNM 路徑 2.AJCC 7th TNM (Tumor-Node-Metastasis) Stage 3.The Child-Pugh stage of Liver cirrhosis 修訂抗癌藥物處方 診療指引 1. 新增 TNM 治療路徑 診療指引 1. 新增術前建議評估 :Chest x-ray Cardio echo 2. 修訂 Strategy for staging and treatment assignment in patients diagnose with HCC according to the BCLC proposal 流程圖 3. 新增 BCLC classification B-2 B-3 B-4 B-6~7 B-8~9 B-5 B-2 B-7 B 年 診療指引 1. 刪除 : 做多次稀釋檢查 (multiple dilution) B 術前建議評估 -Lung function test Chest x-ray Cardio echo

42 肝癌修訂記錄修訂日期修訂內容摘要修訂頁次版本修改為開刀術前建議評估 -Lung function test Chest x-ray Cardio echo 3. 刪除 : ( 目前為每個月第二周禮拜二上午及第四周禮拜五下午 )

43

44 一 肝癌診斷導引 疑似病例 B-1 a. 影像學檢查 :Abdomen echo 或 CT 或 MRI b. 甲種胎兒蛋白檢查或 c. 組織學檢查 : 細針穿刺細胞學或切片病理學檢查 細胞學或病理診斷有且為確定診斷進入肝癌治療 細胞學或病理學檢查未能確診, 或因特殊原因未做細胞學或病理學檢查 未發現腫瘤 非惡性腫瘤或無法確定 甲種胎兒蛋白 400ng/ml, 腫瘤 1cm, 無其他癌症, 且無急性肝炎發作或懷孕 甲種胎兒蛋白 : 400ng/ml, 腫瘤 1cm, 但同時有其他癌症或急性肝炎發作 <400ng/ml, 影像學無法分辨良惡性 腫瘤 1cm 有影像學或臨床資料足以診斷 臨床資料不足以診斷 門診追蹤, 每 3 個月定期追蹤甲種胎兒蛋白及腹部超音波 重做細胞學或切片病理學檢查 肝癌團隊會議 進入肝癌治療規劃

45 B-2 二 肝癌治療前評估項目建議檢查清單 ( 一 ) 病因 : HBsAg Anti-HCV 飲酒及酗酒史 肝硬化家族史 Option: HBeAg HBeAb HBV-DNA HCV-RNA ( 二 ) 診斷依據 : 1. 腫瘤標記 : 甲種胎兒蛋白 (alpha-fetoprotein), 其他 CEA Ca 影像檢查 :CT 或做 MR with enhancement dynamic is phase 三 建議診斷 ( 依據共識會議診斷 ) ( 一 ) 細針抽吸細胞學診斷 ( 二 ) 管針切片病理學檢查 四 功能評估 : ( 一 )Liver function Evaluation: 膽色素 白蛋白 凝血酶原時間 GOT GPT 腹水 肝昏迷 ( 二 )Performance :WHO Performance Scale (ECOG) ( 三 )Routine exam: EKG BUN Creatinine CBC urine stool 開刀術前建議評估 -Lung function test Chest x-ray Cardio echo 五 肝癌分級 :Staging and TNM classification 影像學檢查含 : 1. 基本之胸 腹部 X 光片 2. 腹部超音波, 有顯影之腹部電腦斷層掃瞄或磁振掃瞄 ( 在開始治療之前 ), 血管攝影 ( 可與治療同時安排 ) 等評估腫瘤大小 腫瘤 侵犯 及腹部淋巴節轉移之檢查 3. 核醫科骨骼掃瞄 (Bone scan) 及正子電腦斷層掃描 PET( 高度懷疑儘可能檢查 ) --- 建議轉高醫接受此檢查 六 肝癌各種治療法適應症指引, 有任何不確定或疑慮者, 請會診肝癌團隊會議, 肝癌各種 治療可單獨使用或合併治療 七 手術切除 : 需符合下列條件 ( 一 ) 單一肝癌或多發位於同一肝葉且少於三個之肝癌 ( 二 ) 肝功能 Child pugh classification A, 或可施行小範圍切除之 Child pugh classification B

46 ( 三 ) 無其他不適合手術之病況 4. 主治醫師認為手術對病患病情控制較有利時, 仍可與病人討論後採用手術治療八 局部消除治療 : 最大直徑小於三公分, 少於三個之肝癌 ; 或單一 5 公分以下肝癌, 無嚴重出血傾向且可在超音波或電腦斷層導引下施 行者 肝能 child-pugh classification A 或 B, 及部分 C 者 ( 一 ) 經皮藥物注射治療 (PEI): 大型肝癌一般不建議, 但可施行血管內肝癌注射者或特殊情況時亦可嘗試, 可與其他治療併用為輔助 治療 ( 二 ) 高週波治療 (RFA) 及微波凝固治療 (micro-wave): 肝功能及血液凝固能力要求較經皮藥物注射治療為嚴格 大型肝癌雖亦可使用, 但最好在全身麻醉下施行, 需可承受麻醉者方可使用 ( 三 ) 經導管動脈栓塞術 : 為姑息性治療, 腫瘤數目範圍大小較無限制 肝功能 Child pugh A 及 B 之早期, 無主肝門靜脈侵犯者 ; 無肝 腦病變或嚴重腹水, 總膽色素需在 3mg/dl 以下, 但總膽管阻塞者例外 需先評估出血傾向及血液凝固時間 ( 四 ) 放射線治療 : 任何可定位之病灶均可施行, 通常為合併栓塞之輔助治療或在上述治療不適合時, 做為主要治療適應症如下 : 無法手術切除或經導管動脈栓塞術的原發部位, 肝癌轉移性病灶, 肝門靜脈侵犯, 總膽管侵犯 --- 建議轉高醫接受此治療 ( 五 ) 化學或標靶治療 : 無法施行根除性治療且無法或不適合栓塞之肝癌, 或併發多發轉移性病灶者 --- 建議轉高醫接受此治療 1. 動脈內灌注化學治療 2. 全身靜脈化學治療 3. 口服藥物化學治療 4. 標靶治療或實驗用藥 ( 六 ) 肝臟移植 : 需接受根除性治療, 但肝功能不足無法手術者, 而全身狀況可接受麻醉手術者, 需無遠處轉移且影像學上沒有血管侵 犯 --- 建議轉高醫接受此治療 1. 全肝 ( 屍肝移植 ): (1) 單一肝癌, 最大直徑小於 5 公分 (2) 多發性腫瘤, 小於或等於 3 顆, 最大直徑小於 3 公分 2. 活體肝臟移植 : (1) 單一肝癌, 最大直徑小於 6.5 公分 (2) 多發性腫瘤, 小於或等於 3 顆, 其中最大肝癌不大於 4.5 公分或三顆直徑總和不大小於 8 公分 B-3

47 九 -1 肝癌治療流程圖 : 確診病例 B-4 肝功能及影像學評估 1.Child-pugh C 或 Child-pugh A-B, 但肝癌位置 數目無法接受根治性治療 2. 全肝移植 ( 屍肝 ): 單一肝癌, 最大直徑 <5cm 或多發性腫瘤少於等於 3 個, 最大直徑 <3cm, 無血管侵犯及無遠處轉移 3. 活體肝臟移植 : 單一肝癌最大直徑不超過 6.5 公分, 多發性腫瘤不超過三顆, 三顆直徑不大於 8 公分 ( 其中最大肝癌不大於 4.5 公分 ) 單一肝癌 5cm 或 多發但少於 3 顆於同一肝葉或 無轉移或位於同一小葉或 無主要血管及門靜脈侵犯 治療後經醫師評估後可行 curative 治療 單一肝癌 >5cm 或 兩葉多發性肝癌, 或 主要門靜脈或其他主要血管侵犯, 或有遠處轉移病灶或 肝功能或全身狀況不適合施行根除性治療 非主門靜脈侵犯 Child-pugh A-B 經導管動脈腫瘤栓塞術 標靶治療 放射線治療 主門靜脈侵犯 Child-pugh A-B 標靶治療 放射線治療 臨床試驗 動脈或全身化學治療 Childpugh C 醫師評估後無法行 curative 治療 肝臟移植 * 手術切除 * 局部消除治療 * 酒精注射 * 高週波微波治療 支持性療法 支持性療法標靶治療

48 九 -2 肝癌治療流程圖 : B-5 TNM Directed T1 T2 T3 or T4 N1 or M1 1. 治癒性治療 : Resection Local ablation 2. 無法進行治癒性治療 : TACE 其他替代治療 腫瘤數 3 個以內儘可能治癒性治療 : TACE Combined Therapy TACE Combined therapy Irradiation Chemotherapy Targeting therapy Resection when possible Irradiation Targeting therapy Local or systemic Chemotherapy Single may try curative therapy

49 十 HCC Post- treatment Follow Up Flowchart ( 一 ) 追蹤影像 : B-6 OP RFA PEI TACE(TAE) ( 首次療程 ) 2 個月內 F/U Abd echo CT MRI 1 年內 ( 二 ) 追蹤 AFP elevated: F/U Abd echo CT MRI 需 3 次或以上 第一次治療前 AFP>20ng/ml 的肝癌病人有行 ( 首次療程 ) 2 個月內 F/U AFP elevated. 1 年內 F/U AFP elevated 需 3 次或以上

50 B-7 十一 分期 : 1.Strategy for staging and treatment assignment in patients diagnose with HCC according to the BCLC proposal

51 2.AJCC7th TNM (Tumor-Node-Metastasis) Stage: TX T0 T1 T2 T3a T3b T4 Primary Tumor (T) Primary tumor cannot be assessed No evidence of primary tumor Solitary tumor without vascular invasion Solitary tumor with vascular invasion or multiple tumors none more than 5 cm Multiple tumors more than 5 cm Single tumor or multiple tumors of any size involving a major branch of the portal vein or hepatic vein Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum. B-8 NX N0 N1 Regional Lymph Nodes (N) Regional lymph nodes cannot be assessed No regional lymph node metastasis Regional lymph node metastasis M0 M1 Distant Metastasis (M) No distant metastasis (no pathologic M0; use clinical M to complete stage group) Distant metastasis A NATOMIC S TAGE / P ROGNOSTIC G ROUPS CLINICAL PATHOLOGIC GROUP T N M GROUP T N M I T1 N0 M0 I T1 N0 M0 II T2 N0 M0 II T2 N0 M0 IIIA T3a N0 M0 IIIA T3a N0 M0 IIIB T3b N0 M0 IIIB T3b N0 M0 IIIC T4 N0 M0 IIIC T4 N0 M0 IVA Any T N1 M0 IVA Any T N1 M0 IVB Any T Any N M1 IVB Any T Any N M1

52 3.Barcelona-Clinic Liver Cancer (BCLC) classification Stage Tumor Features Child-Pugh Score Performane Status Stage 0 Single 2cm Carcinoma in situ Stage A Single 5cm or 3 nodulars 3cm Test Child-Pugh A 0 Child-Pugh A-B 0 B-9 Stage B Single>5cm or Child-Pugh A-B 0 Multinodulars Stage C Portal invasion N1,M1 Child-Pugh A-B 1-2 Stage D Any Child-Pugh C 3-4 *BCLC 期別摘錄規則依據行政院衛生署國民健康局書函 ( 發文字號 : 國健癌字第 號 ) 4.The Child-Pugh stage of Liver cirrhosis Score Total bilirubin (mg/dl) < >3.0 Albumin (g/dl) > <2.8 Ascites None Easily controlled Poorly controlled Encephalopathy None Gr1~2 Gr3~4 Prothrombin time ( >normal time,sec ) <4 sec 4-6 sec >6 sec

53 Total score: Child A: 5-6 Child B: 7-9 Child C: B-10

54 B-11 ( 十 ) 抗癌藥物治療處方 :--- 建議轉高醫接受此治療 1.When WBC<3000/UL,ANC<1500/mm,PLT< /UL use with caution!! 2.Emotic pervention or control 3.Pre-treatment Note (1)Primperan 1Amp+N/S 50ml IVD prevent of vomiting before C/T. (2)Infusion for at least one hour (3)Treatment cycle maybe combined or continued when treatment cycle completed Chemotherapy drugs: way be used single or in combination 4. 配制化學藥物溶液為 N/S D5W (1)5FU (50~500mg)/m 2 (2)Epirubicin (10~40mg)/m 2 (3)Mitomycin C(2~10mg)/m 2 (4)Cisplatin(2-40mg)/m 2 (5)Oncovin(2mg)/m 2 (6)Leucovorin(15-100mg)/m 2 (7)VP-16(50-100mg)/m 2 (8)Experiment agent or Targeting therapy 5.Current used Regimens Regimen I (A) Intra-hepatic and Subselective intra-aortic infusion --- Subselective intra-aortic --- Continuous infusion of 5FU (50~250mg) a day using a portable pump Regimen I (B) Intermittent one shot of Epirubicin (10~20mg) + Mitomycin C(2~8mg) Regimen I (C)

55 Continuous infusion of 5FU (50~250mg) a day using a portable pump Intermittent one shot of Epirubicin (10~20mg) + Mitomycin C(2~8mg) regimenⅡ Intermittent one shot of Oncovin(2mg) RegimenⅢ Intermittent one shot of Cisplatin(10-30mg) RegimenⅣ Day1 VP-16(50mg~mg) 30min + Cisplatin(150mg~mg) 30min + Epirubicin (60mg~mg) 30min Day2 5FU(500mg- mg) 24hr 一天 B-12 每 15 天為 1 cycle( 每 15 天打一次 ) Regimen I(A): --Intra-hepatic artery Chemotherapy A -- 1 st week 5FU(50-500mg) 2 nd week 5FU(50-500mg)+Epirubcin(10-40mg) 3 rd week 5FU(50-500mg) 4 th week 5FU(50-500mg)+Epirubcin(10-40mg)+Mitomycin-C (2-10mg) Regimen I(B): Cisplatin(2-40mg) in N/S or D5W 150cc keep 150CC/hr 5 days 4weeks 5FU(50-500mg) + Leucovorin ( mg)in N/S or D5W 250cc keep 50CC/hrfor total 5hr 5 days 4weeks Regimen I(C): Cisplatin(2-40mg) in N/S or D5W 150cc keep 150CC/hr 5 days 4weeks Mitomycin-C(2-10mg) in N/S or D5W 150cc keep 150CC/hr 5 days 4weeks 5FU(50-500mg) + Leucovorin ( mg)in N/S or D5W 250cc keep 50CC/hrfor total 5hr 5 days 4weeks -- Intra-hepatic artery Chemotherapy B--

56 Regimen I(A): Cisplatin(2-40mg) in N/S or D5W 50CC KEEP 100CC/HR 5 days 5FU(50-500mg) in N/S or D5W 250cc KEEP 10CC/HR 5 days 與 Leucovorin ( mg) +N/S100CC KEEP 5CC/HR 5 days 同步使用 Regimen I(B): Cisplatin(2-40mg) in N/S or D5W 50CC KEEP 100CC/HR 5 days Mitomycin-C (2-10mg) in N/S or D5W 50CC KEEP 100CC/HR 5 days 5FU(50-500mg) in N/S or D5W 250cc KEEP 10CC/HR 5 days 與 Leucovorin ( mg) +N/S100CC KEEP 5CC/HR 5 days 同步使用 B-13 Systemic Chemotherapy therapy (concesus Date: ) (1) Doxorubicin(or Epirubcin) is current acceptable mono-chemotherapy (2) Encourage patents who are suitable for chemotherapy enter clinical trial (3) All other therapy stated as experiment therapy Systemic oral chemotherapy (1) 5FU 200mg-400mg qd in divided dose Systemic Chemotherapy therapy (1) Nexavar(sorafenib) 2# -4#/day in divided dose

57 Colon Rectal Cancer Treatment Guideline KMHK

58 大腸癌修訂紀錄 修訂日期修訂內容摘要修訂頁次版本 97 年 98 年 99 年 100 年 101 年 102 年 大腸癌診療指引新制訂 多科會議討論檢視後未修改 多科會議討論檢視後未修改 多科會議討論檢視後未修改 (1) 大腸直腸癌 MONITORING/SURVEILANCE Colonscopy 2-5 years: Obstruction lesion for new lesion, Q3-6m,Q12m 改 Q5Y (2) 結腸癌追蹤準則 : 對於有高度復發危險者, 腹部及骨盆腔電腦斷層檢查, 連續執行三年改二年 (3)High Risk Stage II or Stage III 門診第一線用藥準則 (1): 5FU 500 mg/m 2 + Leucorvin 100mg/ m 2 Weekly for 6 of 8 weeks 改 Weekly for 6 of 8 weeks2-3 cycle (4)High Risk Stage II or Stage III IV 門診第一線用藥準則 (3): Capecitabine 1250 mg/m 2 劑量改 mg/m 2 bid(stage II 需自費 ) (5) 直腸癌治療準則 Lesion 5cm 改 8cm (6) 直腸癌 Stage B1 改 T2N0M0, 治療 Transanal or posterior local excision + post-op radiotherapy and chemotheraopy 刪除 chemotheraopy 新增 LAR or APR (7) 直腸癌 Stage B2 改 T3N0M0, Stage C 改 T1-3N1-2M0,Pre-operative chemotherapy (MMC and 5-FU) 改 LV and 5-FU 新增 LAR or APR (8) 直腸癌 Stage B3, C3 T4 N0-2 M0 治療準則 Pre-op chemotherapy + radiotherapy, then AP or low anterior resection ± intraoperative brachytherapy 改 Pre-op chemotherapy + radiotherapy, then OP or low anterior resection ±then RT (1) 修訂 Pedunculated or Sessile polyp(adenoma [tubular, Tubulovillous,or Villous]) with Invasive cancer 治療 準則 (2) 修訂 Colon cancer Appropriate for Resection(non- metastatic) 治療準則 (3) 修訂 Patient appropriate for intensive therapy (metastasis) 治療準則 C-3 C-4 C-6 C-7 C-11 C-12 C-12 C-14 C-6 C-7 C-10~

59 103 年 104 年 105 年 (1) 修訂 Pedunculated or Sessile polyp(adenoma [tubular, Tubulovillous,or Villous]) with Invasive cancer 治療 C-2 準則 (2) 修訂 Suspected or proven metastatic adeno- carcinoma form large bowel (Duke`s D or stage IV) 治療準則 C-3 (3) 修訂 Colon cancer Appropriate for Resection(non- metastatic) 治療準則 C-4 (4) 修訂大腸癌 MONITORING/SURVEILANCE Abdominal CT or sonography 2 years: Q6m 改 Q3-6m C-5 (5) 修訂直腸癌 MONITORING/SURVEILANCE Pelvis CT/MRI or sonography 2 years: Q6m 改 Q3-6m C-6 (6) 修訂結腸癌第四期合併肝轉移追蹤準則 C-8 (7) 修訂結腸癌 (Adjuvant therapy) 治療準則 C-9~10 (8) 修訂 Patient appropriate for intensive therapy (metastasis) 治療準則 C-12~13 (9) 修訂 Rectal Cancer T3 N0 M0(high risk),t1-3 N1-2 M0 治療準則 C-14 (10) 修訂 Rectal Cancer stage B3,C3 T4N0-2M0 stage D Any T and N M1 治療準則 (1) 增訂大腸直腸癌目的 參考文件 範圍 定義 內容 C-1 (2) 增訂大腸癌簡易治療指引 直腸癌簡易治療指引 C-2~3 (3) 增訂大腸直腸 AJCC 分期 化療藥物 文憲查證 C-18~21 (1) 修訂大腸直腸癌治療準則 COL-1~COL-13 REC-1~REC

60 C-1 1 目的 : 高雄市立小港醫院大腸直腸癌擬參考相關國內外治療指引與相關文獻, 依據現有的設施 健保給付制度, 大腸直腸癌團對相關研究成果與臨床經驗修訂完成 高雄市立小港醫院大腸直腸癌之診療共識 2 範圍 : 大腸直腸癌治療 3 參考文件 : 3.1 National Comprehensive Cancer Network. Clinical Practice Guideline in Oncology:Colon Cancers V National Comprehensive Cancer Network. Clinical Practice Guideline in Oncology:Rectal Cancers V 定義 : 泛指臨床科醫療人員皆可參考適用 5 內容 : 5.1 大腸直腸癌診斷及評估 5.2 糞便潛血反應 : 為大腸直腸癌篩檢廣泛使用之初步檢查方式, 以檢驗大便中是否有潛血反應 5.3 肛門指診 : 病人不需要任何準備, 由醫師戴手套以 Xylocaine Jelly 潤滑右手食指慢慢插入至直腸 7~8 公分, 直腸癌患者一半以上可以摸到硬塊, 是最簡單的檢查方法 5.4 肛門鏡檢 (Anoscopy): 長約 8 公分, 屬於硬的管狀器械, 由肛門插入以肉眼直接檢查 5.5 直腸乙狀結腸鏡檢 (Sigmoidoscopy): 此乃利用約 60 公分長的腸鏡, 從肛門進入直腸乙狀結腸作診斷, 約有 60% 的結腸癌可由此法發現, 檢查時應使肌肉放鬆, 採左側臥或膝胸臥式 5.6 結腸鋇劑灌腸攝影術 : 須做清潔灌腸後, 從肛門灌入鋇劑, 簡單省時, 對於結腸內之病灶, 雙對比鋇劑照影可偵測出較小的病變 5.7 大腸鏡檢查 (Colonoscopy): 須做清潔灌腸後, 由肛門進入結腸, 直接觀看整條大腸黏膜內部情形, 若發現瘜肉可同時切除, 如無法切除必須切片檢查, 且再確認其他結腸處有無同時發生之腫瘤病變 5.8 組織切片檢查 (Bioposy): 使用內視鏡檢查時對可疑的部分取出體外, 再作組織切片, 以判定是否為惡性腫瘤 亦可先行瘜肉切除再作切片, 以 確定是否有惡性變化及侵蝕至黏膜下肉層

61 C 腫瘤記號蛋白 (CEA): 又稱腫瘤胚胎抗原, 係從大腸直腸癌細胞分離出來的蛋白, 它在血中濃度會隨著大腸直腸癌的發生而升高, 臨床上腫瘤記 號蛋白用於手術後, 大腸直腸癌有否局部再發或遠端轉移之偵測參考 5.10 腹部及骨盆腔之電腦斷層掃描 (Abdominal and Pelvic CT): 藉由腹部及骨盆腔之電腦斷層掃描檢查, 可以整體評估腫瘤所在位置, 和腹腔與 骨盆腔內腫瘤細胞侵犯鄰近組織與器官的情形, 以及是否已有肝臟等部位之轉移 5.11 核磁共振掃描 (MRI): 與電腦斷層掃描同為影像學之檢查, 當上述影像學檢查無法確定診斷時, 或病人因腎功能不全或對於電腦斷層顯影劑過 敏時使用, 屬於第二線的檢查, 用來評估直腸癌局部侵犯深度及 CCRT 之反應 5.12 胸部 X 光檢查 (Chest X-ray ): 胸部 X 光片可以初步篩檢肺部有無病後灶, 評估腫瘤細胞是否已有肺部轉移的情形 5.13 全身正子攝影 (PET-CT): 利用腫瘤組織對放射性藥物 ( 氧化去氧葡萄糖 ) 的吸收與代謝, 轉換成體內分布影像, 並結合電腦斷層, 達到準確定 位的功能, 屬全身性的檢查 此檢查雖然比單獨電腦斷層掃描或單獨一正子放射更靈敏, 但仍有約 10 % 的偽陰性或偽陽性發生, 並非常規術 前檢查 5.14 治療準則 大腸癌簡易治療指引 AJCC/ 治療 OP C/T R/T Target 第 0 期 大腸鏡息肉切除或手術切除後觀察 第一期 (pt1-2n0) 手術 定期追蹤 第二期 low risk 手術 定期追蹤或輔助性化療 (pt3n0) High risk 手術 輔助性化療 第三期 (pt1-4,n1-2) 手術 輔助性化療

62 C-3 可切除 原發處和轉移處同時切除 術前化療再手術 化學治療 第四期 (M1) 不可切除 原發處切除 化學治療 轉移處切除 化學治療 + 標靶治療 + 放射線治療 再評估轉移處是否可切除 原發處有阻塞症狀時先行腸道切除 化學治療 + 標靶治療 + 放射線治療 *intraoperative radiation therapy(iort),if available,should be considered for patients with T4 or recurrent cancers as an additional boost. 直腸癌簡易治療指引 stage Op C/T R/T T/T 第 0 期 大腸鏡息肉切除或手術後觀察 第一期 (pt1-2,n0) 1. 經腹部手術 Stage I 觀察 2. 經肛門手術 T1 N0 Margin negative 觀察 T1,N0 with risk factor T2,N0 經腹部手術 第二期 (pt3-4,n0) 第三期 (Any pt,n1-2) 第三期 pt4 and /or 局部無法切除 1 根除性手術放射及化學治療 (CCRT) 術後輔助性化學治療 2 放射及化學治療 (CCRT) 根除性手術術後輔助性化學治療 放射及化學治療 (CCRT) 根除性手術術後輔助性化學治療

63 原發處和轉移處同時切除 第四期轉移型 ( 可切除 ) 術前化療再手術 原發處切除 化學治療 化學治療 轉移處切除

64 Colon Cancer Treatment Guideline 結腸癌治療準則

65

66 ( 須轉介高醫檢查 )is not routinely

67 ( 須轉介高醫檢查 )is not

68

69

70

71

72

73

74

75

76

77 Colon Cancer Treatment Guideline 結腸癌治療準則 (Follow up) MONITORING / SURVEILANCE Pretreatment 2 years 2-5 years >5 years Physical exam, including DRE ˇ Q3m Q6m Q12m Stool occult blood test ˇ Q12m CBC + panel A ˇ Q3-6m Q6m Q12m CEA ˇ Q3m Q6m Q12m Chest X-ray ˇ Q6m Q6m Q12m Abdominal CT or sonography (for colon cancer) Pelvis CT / MRI or sonography (for rectal cancer) ˇ Q3-6m Q12m ˇ Q3-6m Q12m Colonscopy ˇ Q12m Q5Y Q5Y

78 RECTAL CANCER

79 Rectal Cancer Treatment Guideline 直腸癌治療準則

80

81

82

83

84

85

86

87

88

89

90

91 大腸直腸癌 AJCC 分期

92

93 5.16 大腸直腸癌化療藥物 5-FU/LV (slv5fu2) 1 mfolfox6 2.3 FOLFIRI 4 XELOX 5.6 Xeloda 7 Leucovorin 400 mg/m2 5-FU 400 mg/m2 5-FU 2400 mg/m2 Oxaliplatin 85 mg/m2 Leucovorin 400 mg/m2 5-FU 400 mg/m2 5-Fu 2400 mg/m2 Irinotecan 180 mg/m2 Leucovorin 400 mg/m2 5-Fu 400 mg/m2 5-FU 2400 mg/m2 Oxaliplatin 130 mg/m2 Xeloda mg/m2 po Xeloda mg/m2 po UFUR 8.9 FOLFOX4 15 Avastin 10 Erbitux 11 UFUR mg po Oxaliplatin 85 mg/m2 Avastin 劑量 5mg/kg Erbitux 為水劑 500 Leucovorin 200 mg/m2 for 2days 5-FU 400 mg/m2 for 2days 5-Fu 600 mg/m2 for 2days mg/m2 CCRT: 1.RT+5-FU/Leuconvorin 12 : 5-FU400mg/m2 iv bolus + Leuconvorin20 mg/ m2 iv bolus for 4 day during week 1 and 5 of RT 2.RT+Capecitabine : Capecitabine 825mg/m2 twice daily 5 days/week + RT 5weeks

94 文獻查證 : 1 Haller DG, Rothenberg ML,Wong AO, et al. Oxaliplatin plus irinotecan compared with irinotecan alone as second-line treatment after single agent fluoropyrimidine therapy for metastatic colorectal carcinoma. J Clin Oncol 2008;26: Maindrault-Goebel F, degramont A, Louvet C, et al.evaluation of oxaliplatin dose intensity in bimonthly leucovorin and 48-hour 5-fluorouracil continuous infusion regimens (FOLFOX) in cancer. Annals of Oncology 2000;11: pretreated metastatic colorectal 3 Douillard JY, Siena S, Cassidy J, et al. Randomized,phase III trial of panitumumab with infusional fluorouracil,leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study.j Clin Oncol 2010;28: Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecanrefractory metastatic colorectal cancer. N Engl J Med 5 Emmanouilides C, Sfakiotaki G, Androulakis N, et al.front-line bevacizumab in combination with oxaliplatin,leucovorin and 5-fluorouracil (FOLFOX) in patients with metastatic colorectal cancer: a multicenter phase II study. BMC Cancer 2007;7:91. 6 Douillard JY, Siena S, Cassidy J, et al. Randomized,phase III trial of panitumumab with infusional fluorouracil,leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study.j Clin Oncol 2010;28: Falcone A, Ricci S, Brunetti I, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil,leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: The Gruppo Oncologico Nord Ovest. J Clin Oncol 2007;25(13): al, T. K. e. (2002). Efficacy of oral UFT as adjuvant chemotherapy to curative resection of colorectal cancer:multicenter prospective randomized trial. Langenbeck s Arch Surg, 386. doi: /s x 9 at, T. A. e. (2006). Adjuvant Chemotherapy with Uracil Tegafur for Pathological Stage III Rectal Cancer after Mesorectal Excision with Selective 10 Douillard JY, Siena S, Cassidy J, et al. Randomized,phase III trial of panitumumab with infusional fluorouracil,leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 2010;28: European studies showing equivalent efficacy for CapeOX used at a higher dose; however, European patients consistently tolerate capecitabine with less toxicity than American patients. 12 Tepper JE, O'Connell M, Niedzwiecki D, et al. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of Intergroup J Clin Oncol 2002;20: Roh MS, Yothers GA, O'Connell MJ, et al. The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04 [abstract]. J Clin Oncol 2011;29 (suppl):3503.available at: 14 Hofheinz R, Wenz FK, Post S, et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: A randomized, multicentre, noninferiority,phase 3 trial. Lancet Oncol 2012;13: National Comprehensive Cancer Network. Clinical Practice Guideline in Oncology: Colon & Rectal Cancers V National Comprehensive Cancer Network. Clinical Practice Guideline in Oncology: Colon & Rectal Cancer

95 Cancer of the Gastric Treatment Guideline KMHK

96 胃癌修訂紀錄 修訂日期修訂內容摘要 修訂頁次 版本 97 年 98 年 99 年 100 年 101 年 102 年 C 年 104 年 105 年 胃癌診療指引新制訂多科會議討論檢視後未修改多科會議討論檢視後未修改多科會議討論檢視後未修改多科會議討論檢視後未修改 (1)T2,N0 治療 Observe or ECF if received preoperatively or Chemoradiation ( Fluoropyrimidine-based) for selected patients 改 UFUR or follow up (2)T3,T4 or Any T,N+ 治療 ECF if received preoperatively or RT, Gy + concurrent 5-FU-based radiosensitization + 5-FU ± leucovorin 改 Adjuvant Chemotherapy(ECF EOX FOLFOX4 Xeloda UFUR TS1) (1) 因本院沒有再做 Laparoscopic staging 故 Workup 診斷為 Locoregional ( M0 ) 之後 Multidisciplinary Evaluation (1) 增訂目的 參考文件 範圍 定義 內容 (2) 增訂大腸癌簡易治療指引 直腸癌簡易治療指引 (3) 增訂大腸直腸 AJCC 分期 (1) 增訂胃癌簡易版治療準則 Stage 3 Stage 4 (2) 修訂胃癌診療指引共識 C-15 C-22 C-23 C-24 C-23 GAST-1 GAST-2 GAST-3 GAST-4 GAST-5 GAST-6 GAST

97 C-22 目的 : 根據國家衛生研究院 TCOG 所制定的胃癌治療準則, 同時會同各相關次專科根據國人胃癌現況加以修訂, 建立標準化流程, 以藉此提升本院 以及南台灣癌症照護品質 1. 範圍 : 適用本院臨床科醫師 2. 參考文獻 : 2.1.TCOG 胃癌工作群編撰小組 (2012) 胃癌臨床診療指引 苗栗縣 國家衛生研究院 2.2.National Comprehensive Cancer Network. Clinical Practice Guideline in Oncology:Gastric Cancer V 定義 : 4.1 權責 : 臨床科學相關科系醫療人員 4.2 修訂時機 : 定期修訂一次, 但當 TCOG 胃癌臨床診療指引有重大修訂或文獻有重大結論時, 可另行召開診治共識修訂會 4.3 修訂依據 : 主要以最新版的 TCOG 胃癌臨床診療指引為依據, 以最新文獻證據為輔, 並參考團隊診療資料庫的數據分析及研究成果 5. 內容 : 5.1 胃癌簡易版治療準則 AJCC/ 治療 OP C/T R/T Target Hospice Stage 0 ESD or EMR ( 轉高醫 )Gastrectomy Stage 1 ESD or EMR ( 轉高醫 )Gastrectomy Stage 2 Gastrectomy Preoperative Chemotherapy: 1.Fluorouracil+ Cisplatin 2.Cisplatin+Capecitabine( 口服 ) 3.Oxalipltin+Capecitabine( 口服 ) 4.Oxalipltin+Fluorouracil+Leucovorin Perioperative Chemotherapy: 1.Fluorouracil+ Cisplatin CCRT

98 C-23 2.Epirubicin+Cisplatin+Xeloda( 口服 ) 3.Epirubicin+Oxaliplatin+Xeloda( 口服 ) Stage 3 Gastrectomy Preoperative Chemotherapy: 1.Fluorouracil+ Cisplatin 2.Cisplatin+Capecitabine( 口服 ) 3.Oxalipltin+Capecitabine( 口服 ) 4.Oxalipltin+Fluorouracil+Leucovorin Perioperative Chemotherapy: 1.Fluorouracil+ Cisplatin 2.Epirubicin+Cisplatin+Xeloda( 口服 ) 3.Epirubicin+Oxaliplatin+Xeloda( 口服 ) 4.TS-1( 自費 ) Stage 4 Gastrectomy 1.Fluorouracil+ Cisplatin 2.Epirubicin+Cisplatin+Xeloda( 口服 ) 3.Epirubicin+Oxaliplatin+Xeloda( 口服 ) 4.Epirubicin+Oxaliplatin+Fluorouracil 5.Docetaxel+Cisplatin+Fluorouracil 6.Oxalipltin+Fluorouracil+Leucovorin 7. TS-1( 自費 ) 8.Paclitaxel,Taxol CCRT Trastuzumab Symptomati care

99 5.2 胃癌分期 C-24