高雄市立小港醫院 ( 委託財團法人高雄醫學大學經營 ) 107 年癌症診療指引 目 診療指引修訂實證文獻參考來源 Page 1 錄 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

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1 發行日期 :2018 年 7 月 發行版次 : 第 1 版 編輯人員 : 侯明鋒 莊捷翰 吳政毅 王遜模 陳煌麒 蔡東霖 鐘堉緁 梁博程 林宜竑 陳映哲 蘇家弘 王秋 麟 張慧名 沈榮宗 楊凱富 唐世豪 方本詞 李欣樺 黃憶如 艾紀瑩 王亞婷 黃惠娟 洪麗君 黃麗如 賴妙君 張玲瑄

2 高雄市立小港醫院 ( 委託財團法人高雄醫學大學經營 ) 107 年癌症診療指引 目 診療指引修訂實證文獻參考來源 Page 1 錄 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 Gynecologic Cancer 婦癌 Cervical Cancer 子宮頸癌 Endometrial Cancer 子宮內膜癌 Ovarian cancer 卵巢癌 A A-1 A-24 A-30 A-32 B B-1 C C-1 C-14 C-34 D D-1 E E-1 E-10 E-19

3 Cancer of the Head and Neck 頭頸癌 Cancer of the Oral Cavity 口腔癌 Nasopharyngeal carcinoma 鼻咽癌 Urinary tract cancer 泌尿道癌 Bladder cancer 膀胱癌 Prostate cancer 攝護腺癌 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 F F-1 F-3 G G-1 G-14 H H-1 H-4

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5 Cancer of the Lung Treatment Guideline KMHK 初訂日期 97 年 1 月 1 日 修訂日期 年 6 月 5 日

6 肺癌修訂記錄 修訂日期 修訂內容摘要 修訂頁次 版本 97 年 98 年 99 年 100 年 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 年 *non-small cell lung cancer 1. 修訂 non-small cell practice guideline 圖表中 initial evaluation 項目將原有的 CXR Abdominal sonography 刪除 2.stage I II 的 treatment plan 改為 consult chest surgery to evaluate the indication f surgery ± chemotherapy chemadiation 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 Metastatic disease 改為 N2 的 treatment plan 4. 修訂 small cell practice guideline 圖表中 initial evaluation 項目將原有的 CXR Abdominal sonography 刪除 A 年 *non-small cell lung cancer 1. 新增 surgical explation and resection + mediastinal LN dissection systematic LN sampling 後 stage IA 到 IIIA 的 margin positive 與 negative 的治療 2. 修訂 stage IIIA 中 N2-metastatic 的 treatment 3. 新增 stage IIIB 治療流程之圖表 4. 修訂 NSCLC 中新增 stage IV,M1a 與 M1b 的 pretreatment evaluation 圖表 5. 新增 EGFR mutation 之治療流程 6.perfmance status 0-4 建議治療方式圖表 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 3. 新增 CCRT 原則 A-2 A-3 A-2 A-3 A-4 A-5 3.0

7 肺癌修訂記錄 修訂日期 修訂內容摘要 修訂頁次 版本 103 年 *non-small cell lung cancer 新增 stage IIB stage IIIA 為 unresectable disease 治療流程 A-6 2. 新增 stage IIIA (N2 N3 nodes negative N2 nodes positive) 治 療流程 A-7 3. 新增 suspected multiple lung cancers 治療流程 4. 新增 metastatic disease 在 adrenal 的治療流程 A-8~A-9 5. 修訂 EGFR mutation positive 治療流程 6. 新增 ALK positive 治療流程 A-10~A 新增 EGFR mutation and ALK negative unknown 治療流程 8. 新增 squamous cell carcinoma first-line therapy 治療流程 A 新增 third-line therapy 治療流程 104 年 1. 修改 Sensitizing EGFR mutation positive,positive 可選這三個藥物 Erlotinib Afatinib Gefitinib A-14 A-4~ A 年 多專科會議討論檢視後未修改 106 年 1. 非小細胞肺癌初步評估加入肺功能 心臟超音波 腹部超音波 腫瘤指數 ( 可考慮 ) 2. 針對高風險 IB-II 期給予輔助型化療 (1) 分化不佳 (2) 血管侵犯 (3) 腫瘤 >4 公分 (4) 臟層肋膜侵犯 (5)Wedge resection (6) 未明淋巴結 3. 全部 Reresection 修改為 resection 4. 非小細胞肺癌, 為分散肺腫瘤, 同側肺葉 (T3, N0) 或同側非原發肺葉 (T4,N0) 手術後為 N0-1, 可行化療 5. 非小細胞肺癌, 第 IV, M1b 期 : 獨立腫瘤, 轉移至其他部位可參考 A-14, 刪除轉移針對腎上腺部分 6. 原 EGFR ± ALK testing should be conduced as part of multiplex/next-generation sequencing 刪除, 修改為 PDL-1 testing 7. 在一線化療前或期間發現 ALK 受體重組, 先行含鉑的化療, 若有 A-7 A-8~9 A-12 A-14 A-15 A-16 A-17 A-18 A-19 A

8 肺癌修訂記錄 修訂日期 修訂內容摘要 修訂頁次 版本 惡化, 可使用 crizotinib, 若有副作用或持續惡化多新增 ceritinib (zykadia 立克癌 ) 之藥物選擇 107 年. 原考慮雙白金類 ±Bevacizumab(Avastin 癌思停 ), 改 Avastin± 雙白金類 1. 修改成 AJCC 8th 版 A-1 A-2 A

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

10 Non-Small Cell Lung Cancer 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 stereotactic ablative radiotherapy (SABR) (refer to KMUH) See stage IIIA (A-7) stage IIIAB(A-10) *Brain MRI 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/ EBUS/EUS(refer to KMUH) *PET/CT scan(refer to KMUH) *Brain MRI (stage II, stage IB) Negative mediastinal nodes Positive mediastinal nodes Operable Medically inoperable See initial treatment and adjuvant treatment(a-3) N0 N1 Definitive RT including SABR Definitive chemadiation See stage IIIA (A-7) stage IIIAB(A-10) Adjuvant C/T f high risk stages IBII A-2

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

12 Non-Small Cell Lung Cancer 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 + thacic inlet f superi sulcus lesions abuttling the spine subclavian vessels (option) *PET/CT scan (refer to KMUH) Superi sulcus tum See A-5 Chest wall See A-5 Proximal airway See A-5 mediastinum Unresectable disease See A-5 Metastatic disease See A-12 A-13 A-4

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

14 Non-Small Cell Lung Cancer 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 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) 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) Extrathacic metastatic disease See A-12 A-13 A-6

15 Non-Small Cell Lung Cancer 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 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 Chemadiation (sequential concurrent) Concurrent chemadiation See A-13 See A-13 T1-2, T3( 7cm), N2 nodes positive *Brain MRI *PET/CT(refer to KMUH) Negative f M1 disease Definitive concurrent chemadiation induction chemotherapy No apparent progression Progression Surgery±chemotherapy±RT Local RT±chemotherapy Systemic See A-12 A-13 Positive See A-12 A-13 T3(invasion), N2 nodes positive *Brain MRI *PET/CT(refer to KMUH) Negative f M1 disease Positive Definitive concurrent chemadiation See A-12 A-13 A-7

16 Non-Small Cell Lung Cancer Clinical Presentation Initial Treatment Adjuvant Treatment N0-1 Chemotherapy See A-13 Separate pulmonary nodule(s), same lobe (T3, N0) ipsilateral nonprimary lobe (T4, N0) Surgery Margin negative (R0) Chemotherapy See A-13 N2 Margins positive (R1,R2) Concurrent chemadiation (if tolerated) See A-13 Stage IV ( N0, M1a) Contralateral lung (solitary nodule) Treat as two primary lung tums if both curable See A-1 Suspected multiple lung cancers (based on the presence of biopsy-proven synchronous lesions histy 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 A-8

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

18 Non-Small Cell Lung Cancer 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 -Thacoscopy N3 positive Definitive concurrent chemadiation - Needle biopsy - Mediastinotomy - Endoscopic ultrasound (EUS) biopsy(refer to KMUH) Metastatic disease See A-12 A-13 - Endobronchial ultrasound (EBUS) biopsy(refer to KMUH) A-10

19 Non-Small Cell Lung Cancer Clinical Assessment Pretreatment Evaluation Initial Treatment Ipsilateral mediastinal node negative (T4, See A-7 Contralateral 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 -Thacoscopy -Needle biopsy node negative Contralateral mediastinal node positive (T4, N3) Ipsilateral mediastinal node positive (T4, N2) Definitive concurrent chemadiation Definitive concurrent chemadiation -Mediastinotomy -EUS biopsy (refer to KMUH) -EBUS biopsy (refer to KMUH) Metastatic disease See A-12 A-13 Stage IV, M1a: Pleural pericardial effusion Thacenfesis pericardiocentesis ± thacoscopy if thacentesis indeterminate Negative Positive See A-7 Local therapy if necessary (e.g. pleurodesis, ambulaty small catheter drainage, pericardial window) + See A-12 A-13 A-11

20 Non-Small Cell Lung Cancer Clinical Assessment Pretreatment Evaluation Initial Treatment Surgical resection of lung lesion Chemotherapy Stereotactic ablative Stage IV, M1b: Solitary site *Pathologic mediastinal lymph node evaluation *Bronchoscopy *Brain MRI *Bone scan(refer to KMUH) Brain Surgical resection followed by whole brain RT (WBRT) stereotactic radiosurgery (SRS) SRS + WBRT (categy 1 f one metastasis) SRS alone T1-2, N0-1; T3, N0; T1-2, N2; T3, N1-2; Any T, N3; T4, Any N radiotherapy (SABR) of lung lesion Chemotherapy See A-14 Surgical resection of lung lesion SABR of lung lesion *PET/CT scan (refer to KMUH) Other site See A-14 A-12

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

22 Non-Small Cell Lung Cancer Systemic Therapy f Metastatic Disease Evaluation Histologic Subtype Metastatic disease *Establish histologic subtype with adequate tissue f molecular testing (consider rebiopsy if appropriate) *Smoking cessation advice, *Adenocarcinoma *Large cell *NSCLC not otherwise specified (NOS) *EGFR mutation testing *ALK testing * PDL-1 testing Sensitizing EGFR mutation positive ALK positive Sensitizing EGFR mutation and ALK negative unknown See A-15 See A-16 See A-17 counseling *Intergrate palliative care Squamous cell carcinoma *Consider EGFR mutation and ALK testing especially in nerver smokers small biopsy, specimens, mixed histology * PDL-1 testing See A-18 A-14

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

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

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

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

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

28 AJCC8th TNM (Tum-Node-Metastasis) Stage: Definition of Primary Tum(T) T Categy TX T0 Tis T1 T1mi T1a T1b T1c T2 T Criteria Primary tum cannot be assessed, tum proven by the presence of malignant cells in sputum bronchial washings but not visualized by imaging bronchoscopy No evidence of primary tum Carcinoma in situ Squamous cell carcinoma in situ (SCIS) Adenocarcinoma in situ (AIS): adenocarcinoma with pure lepidic pattern, 3 cm in greatest dimension Tum 3 cm in greatest dimension, surrounded by lung visceral pleura, without bronchoscopic evidence of invasion me proximal than the lobar bronchus (i.e., not in the main bronchus) Minimally invasive adenocarcinoma: adenocarcinoma ( 3 cm in greatest dimension) with a predominantly lepidic pattern and 5 mm invasion in greatest dimension Tum 1 cm in greatest dimension. A superficial, spreading tum of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tums are uncommon. Tum> 1 cm but 2 cm in greatest dimension Tum> 2 cm but 3 cm in greatest dimension Tum > 3 cm but 5 cm having any of the following features: Involves the main bronchus regardless of distance to the carin, but without involvement of the carina Invades visceral pleura (PL1 PL2) Associated with atelectasis obstructive pneumonitis that extends to the hilar region, involving part all of the lung T2 tums with these features are classified as T2a if 4 cm if the size cannot be determined and T2b if > 4 cm but 5 cm. A-20

29 T2a T2b T3 T4 Tum> 3 cm but 4 cm in greatest dimension Tum> 4 cm but 5 cm in greatest dimension Tum > 5 cm but 7 cm in greatest dimension directly invading any of the following: parietal pleural (PL3), chest wall (including superi sulcus tums), phrenic nerve, parietal pericardium; separate tum nodule(s) in the same lobe as the primary Tum > 7 cm tum of any size invading one me of the following: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina; separate tum nodule(s) in an ipsilateral lobe different from that of the primary Definition of Regional Lymph Node(N) N Categy N Criteria NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in ipsilateral peribronchial and/ ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension N2 Metastasis in ipsilateral mediastinal and/ subcarinal lymph node(s) N3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral contralateral scalene, supraclavicular lymph node(s) Definition of Distant Metastasis(M) M Categy M0 M1 M Criteria No distant metastasis Distant metastasis A-21

30 M1a M1b M1c Separate tum nodule(s) in a contralatearl lobe; tum with pleural pericardial nodules malignant pleural pericardial effusion. Most pleural (pericardial) effusion with lung cancer are a result of the tum. In a few patients, however, multiple microscopic examinations of pleural (pericardial) fluid are negative f tun, and the fluid is nonbloody and not an exudates. If these elements and clinical judgment dictate that the effusion is not related to the tum, the effusion should be excluded as a staging descript. Single extrathacic metastasis in a single gan (including involvement of a single nonregional node) Multiple extrathacic metastases in a single gan in multiple gans AJCC PROGNOSTIC STAGE GROUPS T N M GROUP TX N0 M0 Occult carcinoma Tis N0 M0 0 T1mi N0 M0 IA1 T1a N0 M0 IA1 T1a N1 M0 IIB T1a N2 M0 IIIA T1a N3 M0 IIIB T1b N0 M0 IA2 T1b N1 M0 IIB T1b N2 M0 IIIA T1b N3 M0 IIIB T1c N0 M0 IA3 T1c N1 M0 IIB T1c N2 M0 IIIA A-22

31 T1c N3 M0 IIIB T2a N0 M0 IB T2a N1 M0 IIB T2a N2 M0 IIIA T2a N3 M0 IIIB T2b N0 M0 IIA T2b N1 M0 IIB T2b N2 M0 IIIA T2b N3 M0 IIIB T3 N0 M0 IIB T3 N1 M0 IIIA T3 N2 M0 IIIB T3 N3 M0 IIIC T4 N0 M0 IIIA T4 N1 M0 IIIA T4 N2 M0 IIIB T4 N3 M0 IIIC Any T Any N M1a IVA Any T Any N M1b IVA Any T Any N M1c IVB A-23

32 Small Cell Lung Cancer Diagnosis Initial Evaluation Stage Small cell combined small cell/non-small cell lung cancer on biopsy cytology of primary 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) CT 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-25 *Bone scan (refer to KMUH) *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-27 A-24

33 Small Cell Lung Cancer Stage Additional Wkup *If pleural effusion is present, thacentesis is recommended; if Clinical stage (T1-2, N0) PET/CT (if not previous obtained) Pathologic mediastinal staging is considered See A-26 Limited stage (T any, N any, M0; except T3-4 due to multiple lung nodules that do not fit in a tolerable radiation field) thacentesis inconclusive, consider thacoscopy *Pulmonary function tests (PFTs) (if clinically indicated) *Bone imaging(radiographs MRI) as Limited stage in excess of T1-2, N0 See A-26 appropriate if PET-CT equivocal *Unilateral marrow aspiration/biopsy in select patients Bone marrow biopsy, thacentesis, bone studies See A-27 consistent with malignancy A-25

34 Small Cell Lung Cancer Testing Results Initial Treatment Adjuvant Treatment Pathologic mediastinal staging negative Lobectomy (preferred) and mediastinal lymph node dissection sampling N0 N+ Chemotherapy Concurrent chemotherapy + Clinical stage T1-2, N0 Pathologic mediastinal Good perfmance status (PS 0-2) mediastinal RT Chemotherapy + concurrent thacic RT See A-28 staging positive medically inoperable Po PS (3-4) due to SCLC Chemotherapy ± RT Po PS (3-4) not Individualized treatment due to SCLC including supptive care Good perfmance status (PS 0-2) Chemotherapy + concurrent thacic RT See A-28 Limited stage excess T1-2, N0 Po PS (3-4) due to SCLC Chemotherapy ±RT Po PS (3-4) not due to SCLC Individualized treatment including supptive care A-26

35 Small Cell Lung Cancer Stage Initial Treatment Extensive stage without localized symptomatic *Good PS (0-2) *Po PS (3-4) due to SCLC Combination chemotherapy including supptive care See NCCN Palliative Care Guidelines sites brain metastases *Po PS (3-4) not due to SCLC Individualized therapy including supptive 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 cd compression Chemotherapy± RT to symptomatic sites If high risk of fracture due to osseous structural impairment, consider palliative external-beam RT and thopedic stabilization RT to symptomatic sites befe chemotherapy unless immediate systemic therapy is required. See A-28 Extensive stage with Asymptomatic May administer chemotherapy first, with whole-brain RT after chemotherapy brain metastases Symptomatic Whole-brain RT befe chemotherapy, unless immediate systemic therapy is required A-27

36 Small Cell Lung Cancer Response Assessment Following Initial Therapy Adjuvant Treatment Surveillance After recovery from primary therapy: *Oncology follow-up visits every 3-4 mo *Chest x-ray (optional) *Chest/liver/adrenal CT with IV contrast whenever possible *Brain MRI (preferred) CT with IV contrast whenever possible, if prophylactic cranical irradiation (PCI) to be given *Other image studies, to assess pri sites of involvement, as clinically Complete response partial response Stable disease Limited extensive stage: PCI during y 1-2, at least every 6 mo during y 3-5, then annually -At every visit: H&P, chest imaging, bloodwk as clinically indicated *New pulmonary nodule should initiate wkup f potential new primary *Smoking cessation intervention *PET/CT is not recommended f routine follow-up See A-29 indicated *CBC, platelets *Electrolytic, LFTs, Ca, BUN, creatinine Primary progressive disease See A-24 A-28

37 Small Cell Lung Cancer Progressive Disease Subsequent Therapy/Palliative Therapy PS 0-2 Subsequent chemotherapy (categy 1 f topotecan) palliative symptom management, Continue until two cycles beyond best response progression of disease development of unacceptable toxicity Palliative symptom management, including localized RT to symptomatic sites including localized RT to Relapse primary symptomatic sites progressive disease PS 3-4 Palliative symptom management, including localized RT to symptomatic sites A-29

38 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 chemadiotherapy),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 superi outcome but at the cost of an increased toxicity. 2.Platinum-based regimen is preferred 3.Reference regimens with combination of platinum Etoposide Vinelbine Vinblastine A-30

39 4.Alternative regimens with combination of platinum Paclitaxel -Docetaxel -Pemetrexed 5.High-risk drugs f CCRT Gemcitabine -EGFR-TKI (gefitinib, erlotinib) - Bevacizumab -Doxubicin A-31

40 參考文獻 1. Small Cell Lung Cancer NCCN V from 2. Non-Small Cell Lung Cancer NCCN V4.2017from 3. Paumier, A. and C. Le Pechoux, Radiotherapy in small-cell lung cancer:where should it go Lung Cancer, : Sensen, M., M. Pijls-Johannesma, and E. Felip, Small-cell lung cancer:esmo Clinical Practice Guidelines f diagnosis, treatment and follow-up. Ann Oncol, Suppl 5: v Khan, A.J., P.S. Mehta, T.W. Zusag, et al., Long term disease-free survival resulting from combined modality management of patients presenting with oligometastatic, non-small cell lung carcinoma (NSCLC). Radiother Oncol, :

41 Cancer of the Esophagus Treatment Guideline KMHK 初訂日期 : 年 1 月 1 日 修訂日期 : 年 6 月 5 日

42 食道癌修訂記錄 修訂日期修訂內容摘要修訂頁次版本 104 年第一版依照 NCCN guideline 制定本院治療準則 年多科會議討論檢視後未修改 106 年 1.Endoscopic mucosal resection (EMR) 修改為 Endoscopic resection (ER) 並加入建議 A 分期為 T1a T1b 之附註 (A-29) 2. 分期 Stage I-III (locegional disease)adenocarcinoma See ESOPH-10 改為 See A 分期 Stage IV (metastatic disease) Squamous cell carcinoma See ESOPH-9 改為 See A Multidisciplinary evaluation-consider nasogastric J-tube f preoperative nutritional suppt 增加 PEG 亦可 suppt preoperative nutrition (A-30) 5. 刪除 Squamous cell carcinoma Stage I-III (locegional disease) Medically unfit f surgery surgery not...(a-30) 6. 新增 Non-surgical candidate(refer to KMUH) (A-30) 7. 修改 Squamous cell carcinoma (A-31) Tis 建議行 Endoscopic therapies Esophagectomy A-30 A-31 T1a 建議行 Endoscopic therapies (preferred) esophagectomy T1b, N0 建議行 Eesophagectomy T1b, N+, T2-T4a, N0- N+ 建議行 Chemadiation (Refer to KMUH) esophagectomy T4b(Refer to KMUH) 8. 刪除 A-32 A-33 A-34 頁數全部內容 9.Palliative/Salvage therapy 更改為 Palliative therapy(a32) 10.Esophageal Cancer (squamous cell carcinoma) recurrent Palliative therapy See A-32 ESOPH-9 改為 See A Esophageal Cancer (squamous cell carcinoma) Unresectable locally advanced,

43 食道癌修訂記錄 修訂日期修訂內容摘要修訂頁次版本 107 年 locally recurrent metastatic disease Karnofsky perfmance sce 60% ECOG perfmance sce 2 修改建議 cheotherapy/radiotherapy 更改為 Systemic therapy and/ best supptive care(a33) 12. Esophageal Cancer (squamous cell carcinoma) Unresectable locally advanced, locally recurrent metastatic disease,ecog perfmance sce 2, 改為 3 建議 Best supptive care(a33) 13. Esophageal Cancer Adenocarcinoma Stage I-III (locegional disease) See ESOPH-11 改為 See A35 新增 Non-surgical candidate(refer to KMUH) 移除 Medically unfit f surgery... (A-34) 14. Esophageal Cancer (Adenocarcinoma) Tis T1a 建議行 Endoscopic therapies(preferred) Esophagectomy(A-35) T1b, N0 建議行 Eesophagectomy T1b, N+, T2-T4a, N0- N+ 建議行 Chemadiation (Refer to KMUH) esophagectomy T4b(Refer to KMUH) 1. 刪除 T4b 之 (Refer to KMUH) 改為 Chemadiation Chemotherapy Radiation Best suppt care And/ hospice care clinical trial (refer to KMUH) 加入 R/T 說明 A-33 A-34 A-35 A-31 A

44 Esophageal Cancer Wkup Clinical stage Histologic classification Squamous cell carcinoma See A33 *H & P *Upper GI endoscopy and biopsy * Chest/abdomen CT with al and IV contrast *PET-CT evaluation if no evidence of M1 disease(refer to KMUH) *CBC and chemistry profile Stage I-III (locegional disease) Adenocarcinoma See A37 *Endoscopic resection (ER) is essential f the accurate staging of early stage cancers(t1a T1b) *Nutritional assessment and counseling *Biopsy of metastatic disease as clinically indicated *HER2-neu testing if metastatic adenocarcinoma is documented/suspected *Bronchoscopy, if tum is at above the carina with no evidence of Squamous cell carcinoma See A36 M1 disease *Assign Siewert categy *Smoking cessation advice, counseling, and pharmacotherapy Stage IV (metastatic disease Adenocarcinoma Palliative therapy A-32

45 Esophageal Cancer Histology Clinical stage Additional Evaluation (as clinically indicated) Squamous cell carcinoma Stage I-III (locegional disease) *Multidisciplinary evaluation -Consider nasogastric J-tube PEG f preoperative nutritional suppt Medically fit f surgery See A34 Non-surgical candidate(refer to KMUH) A-33

46 Esophageal Cancer Histology Tum classifications Primary treatment options f medically fit patients Tis Endoscopic therapies Esophagectomy T1a Endoscopic therapies (preferred) esophagectomy Squamous cell carcinoma T1b, N0 Eesophagectomy T1b, N+, T2-T4a, N0- N+ Chemadiation esophagectomy T4b Chemadiation Chemotherapy Radiation Best suppt care And/ hospice care clinical trial (refer to KMUH) 說明 : 因本院無放射治療設備, 故治療需放射線治療及同步化學治療病患協助轉診至高醫或他院治療 A-34

47 Esophageal Cancer Follow-up f squamous cell carcinoma Recurrence Palliative therapy *H & P -if asymptomatic: H & P every Locegional only recurrence: pri esophagectomy, no pri chemadiation Concurrent chemadiation (fluopyrimidine- taxane-based) preferred surgery chemotherapy best supptive care Recurrence See A mo f 1-2y, every 6-12 mo f 3-5y, then annually * Chemistry profile and CBC, as clinically indicated *Imaging study *Upper GI endoscopy and biopsy *Dilatation f anastomotic stenosis *Nutritional assessment and counseling Locegional only recurrence: pri chemadiation, no pri esophagectomy Resectable and medically operable Unresectable medically inoperable esophagectomy Recurrence See A36 See A36 Metastatic disease A-35

48 Esophageal Cancer F squamous cell carcinoma Perfmance status Palliative therapy Unresectable locally advanced, locally recurrent metastatic disease Karnofsky perfmance sce 60% ECOG perfmance sce 2 Systemic therapy and/ best supptive care Karnofsky perfmance sce<60% ECOG perfmance sce 3 Best supptive care A-36

49 Esophageal Cancer Histology Clinical status Additional evaluation (as clinically indicated) Adenocarcinoma Stage I-III (locegional disease) *Multidisciplinary evaluation -Consider nasogastric J-tube PEG f preoperative nutritional suppt -Laparoscopy (optional) if no evidence of M1 disease and tum is at esophagogastric junction(egj) Medically fit f surgery See A38 Chemadiation Chemotherapy Radiation Best suppt care And/ hospice care clinical trial (refer to KMUH) A-37

50 Esophageal Cancer Tum classification Primary treatment options f medically fit patients Tis Endoscopic therapies(preferred) Esophagectomy T1a T1b,N0 Esophagectomy Adenocarcinoma Chemadiation T1b,N+ T2-T4a, N0-N+ Esophagectomy T4b Chemadiation Chemotherapy Radiation Best suppt care And/ hospice care clinical trial (refer to KMUH) 說明 : 因本院無放射治療設備, 故治療需放射線治療及同步化學治療病患協助轉診至高醫或他院治療 A-38

51 Esophageal Cancer Follow-up f adenocarcinomas Recurrence Palliative/salvage therapy *H & P -if asymptomatic: H & P every 3-6 mo f 1-2y, every 6-12 mo f 3-5y, then annually * Chemistry profiles and CBC, as clinically indicated *Imaging studies *Upper GI endoscopy and biopsy *Dilatation f anastomotic stenosis *Nutritional assessment and counseling Locegional only recurrence: Pri esophagectomy, no pri chemadiation Locegional only recurrence: Pri chemadiation, no pri esophagectomy Metastatic disease Resectable and medically operable Unresectable medically inoperable Surgery Chemotherapy Best supptive care Esophagectomy Palliative therapy Recurrence Palliative therapy A-39

52 參考文獻 1. Esophagus Cancer V from 2. van Hagen P, Hulshof MC, van Lanschot JJ, et al.preoperative chemadiotherapy f esophageal junctional cancer. N Engl J Med 2012;366: Tepper J, Krasna MJ, Niedzwiecki D, et al. Phase III trial of trimodality therapy with cisplatin, fluouracil, radiotherapy,and surgery compared with surgery alone f esophageal cancer: CALGB J Clin Oncol 2008;26: Bedenne L, Michel P, Bouche O, et al. Chemadiation followed by surgery compared with chemadiation alone in squamous cancer of the esophagus: FFCD J Clin Oncol 2007;25:

53 Cancer of the Liver Treatment Guideline KMHK 初訂日期 :97 年 1 月 1 日 修訂日期 :107 年 6 月 15 日

54 肝癌修訂記錄 修訂日期修訂內容摘要修訂頁次版本 97 年肝癌診療指引新制訂 98 年 99 年 100 年 101 年 多科會議討論檢視後未修改多 多科會議討論檢視後未修改多 多科會議討論檢視後未修改多 多科會議討論檢視後未修改多 102 年 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

55 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 105 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 (Tum-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 f staging and treatment assignment in patients diagnose with HCC accding to the BCLC proposal 流程圖 3. 新增 BCLC classification 診療指引 1. 刪除 : 做多次稀釋檢查 (multipledilution). 術前建議評估 -Lung function test Chest x-ray B-2 B-3 B-4 B-6~7 B-8~9 B B B-7 B-8 B-2 B4 B7 5.0

56 106 年 107 年 Cardio echo 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 ) 1. 刪除 Child-pugh C 的治療中的標靶治療 2. 非常早期 (0) 新增治療方式為切除 局部消除治療 1. 新增九 姑息性治療 ( 一 ) 經導管動脈栓塞術 ( 二 ) 放射性治療 ( 三 ) 化學或標靶治療 2. ( 三 ) 化學或標靶治療動脈內灌注化學治療 全身靜脈化學治療 --- 建議轉高醫接受此治療 肝癌治療準則 2. 1.AJCC7th 修改為 AJCC8th

57 一 肝癌診斷導引 疑似病例 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 B-1 進入肝癌治療規劃

58 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 )Perfmance :WHO Perfmance 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 ( 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 B-2

59 九 姑息性治療 : ( 一 ) 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 ( 二 ) 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 ( 三 ) 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 1 2 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 十 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 ( 一 ) 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 ( 二 ) 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

60 十一 -1 肝癌治療流程圖 : 確診病例 肝功能及影像學評估分 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 Childpugh C 標靶治療 放射線治療 臨床試驗 動脈或全身化學治療 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 醫師評估後無法行 curative 治療 支持性療法 支持性療法 B-4

61 Hepatocellular carcinoma 十一 -2 肝癌治療流程圖 : TNM Directed T1 T2 T3 T4 N1 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 systemic Chemotherapy Single may try curative therapy B-5

62 Hepatocellular carcinoma 十二 HCC Post- treatment Follow Up Flowchart ( 一 ) 追蹤影像 : OP RFA PEI TACE(TAE) ( 首次療程 ) 2 個月內 F/U Abd echo CT 1 年內 F/U Abd echo CT MRI 需 3 次或以上 ( 二 ) 追蹤 AFP elevated: 第一次治療前 AFP>20ng/ml 的肝癌病人有行 ( 首次療程 ) OP RFA PEI TACE(TAE) 2 個月內 F/U AFP elevated 1 年內 F/U AFP elevated 需 3 次或以上 B-6

63 Hepatocellular carcinoma 十三 分期 :1.Strategy f staging and treatment assignment in patients diagnose with HCC accding to the BCLC proposal Hepatocellular carcinoma Stage:0 PST:0 child-turcotte-pugh:a stage:a-c PST:0-2 child-turcotte-pugh:a B stage:d PST:>2 child-turcotte-pugh:c Very early stage(0) Early stage:a single nodule< 5cm 3 nodules 3cm PST:0 Intermediate stage: B Multinodular, PST:0 Advanced stage:c ptal invasion N1,M1, PST:1-2 Terminal stage:d single< 2cm carcinoma in situ single 3 nodules 3cm TAE TACE Supptive Increased ptal pressure yes care and elevated bilirubin level Association disease no Safenib resection no Liver transplantion(clt LDLT) yes PEI RFA target therapy B-7

64 2. AJCC8th TNM (Tum-Node-Metastasis) Stage: TX T0 T1 T1a T1b T2 T3 T4 Primary Tum (T) Primary tum cannot be assessed No evidence of primary tum Solitary tum 2cm, >2cm without vascular invasion Solitary tum 2cm Solitary tum >2cm without vascular invasion Solitary tum >2cm with vascular invasion, multiple tums,none>5cm Multiple tums,at least one of which is >5cm Single tum multiple tums of any size involving a maj branch of the ptal vein hepatic vein, tum(s) with direct invasion of adjacent gans other than the gallbladder with perfation of visceral peritonem. NX N0 N1 Regional Lymph Nodes (N) Regional lymph nodes cannot be assessed No regional lymph node metastasis Regional lymph node metastasis M0 M1 No distant metastasis Distant metastasis Distant Metastasis (M) A NATOMIC S TAGE / P ROGNOSTIC G ROUPS CLINICAL PATHOLOGIC GROUP T N M GROUP T N M IA T1a N0 M0 IA T1a N0 M0 IB T1b N0 M0 IB Tb N0 M0 II T2 N0 M0 II T2 N0 M0 IIIA T3 N0 M0 IIIA T3 N0 M0 IIIB T4 N0 M0 IIIB 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 B-8

65 3. Barcelona-Clinic Liver Cancer (BCLC) classification Stage Tum Features Child-Pugh Sce Perfmane Status Stage 0 Single 2cm Carcinoma in situ Stage A Single 5cm 3 Stage B Stage C nodulars 3cm Single>5cm Multinodulars Ptal invasion N1,M1 Test Child-Pugh A 0 Child-Pugh A-B 0 Child-Pugh A-B 0 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 Sce Total bilirubin (mg/dl) < >3.0 Albumin (g/dl) > <2.8 Ascites None Easily controlled Poly controlled Encephalopathy None Gr1~2 Gr3~4 Prothrombin time ( >nmal time,sec ) <4 sec 4-6 sec >6 sec Total sce: Child A: 5-6 Child B: 7-9 Child C: B-9

66 ( 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 control 3.Pre-treatment Note (1)Primperan 1Amp+N/S 50ml IVD prevent of vomiting befe C/T. (2)Infusion f at least one hour (3)Treatment cycle maybe combined continued when treatment cycle completed Chemotherapy drugs: way be used single 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)Leucovin(15-100mg)/m 2 (7)VP-16(50-100mg)/m 2 (8)Experiment agent Targeting therapy 5.Current used Regimens Intra-hepatic and Subselective intra-atic infusion B-10

67 Regimen I (A) Continuous infusion of 5FU (50~250mg) a day using a ptable pump Regimen I (B) Intermittent one shot of Epirubicin (10~20mg) + Mitomycin C(2~8mg) Regimen I (C) Continuous infusion of 5FU (50~250mg) a day using a ptable 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) --- Subselective intra-atic --- RegimenⅣ Day1 VP-16(50mg~mg) 30min + Cisplatin(150mg~mg) 30min + Epirubicin (60mg~mg) 30min Day2 5FU(500mg- mg) 24hr 一天, 每 15 天為 1 cycle( 每 15 天打一次 ) Regimen I(A) ---Intra-hepatic artery Chemotherapy A 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 D5W 150cc keep 150CC/hr 5 days 4weeks 5FU(50-500mg) + Leucovin ( mg)in N/S D5W 250cc keep 50CC/hrf total 5hr 5 days 4weeks B-11

68 Regimen I(C) Cisplatin(2-40mg) in N/S D5W 150cc keep 150CC/hr 5 days 4weeks Mitomycin-C(2-10mg) in N/S D5W 150cc keep 150CC/hr 5 days 4weeks 5FU(50-500mg) + Leucovin ( mg)in N/S D5W 250cc keep 50CC/hrf total 5hr 5 days 4weeks --- Intra-hepatic artery Chemotherapy B--- Regimen I(A) Cisplatin(2-40mg) in N/S D5W,50CC KEEP 100CC/HR 5 days 5FU(50-500mg) in N/S D5W 250cc KEEP 10CC/HR 5 days 與 Leucovin ( mg)+n/s100cc KEEP 5CC/HR 5 days 同步使用 Regimen I(B) Cisplatin(2-40mg) in N/S D5W 50CC KEEP 100CC/HR 5 days Mitomycin-C (2-10mg) in N/S D5W 50CC KEEP 100CC/HR 5 days 5FU(50-500mg) in N/S D5W 250cc KEEP 10CC/HR 5 days 與 Leucovin ( mg)+n/s100cc KEEP 5CC/HR 5 days 同步使用 Systemic Chemotherapy therapy (concesus Date: ) (1) Doxubicin( Epirubcin) is current acceptable mono-chemotherapy (2) Encourage patents who are suitable f chemotherapy enter clinical trial (3) All other therapy stated as experiment therapy. B-12

69 (1) 5FU 200mg-400mg qd in divided dose --- Systemic al chemotherapy --- Systemic Chemotherapy therapy (1) Nexavar(safenib) 2# -4#/day in divided dose 參考文獻 1. Hepatobiliary Cancer NCCN V from 2. Song MJ. Hepatic artery infusion chemotherapy f advanced hepatocellular carcinoma.(2015) Wld J Gastroenterol ; 21(13): Tsai W-L, Lai K-H, Liang H-L, Hsu P-I, Chan H-H, et al. (2014) Hepatic Arterial Infusion Chemotherapy f Patients with Huge Unresectable Hepatocellular Carcinoma. PLoS ONE 9(5), Wang.S-N, Chuang. S-C, Lee. K-T,(2014) Efficacy of safenib as adjuvant therapy to prevent early recurrence of hepatocellular carcinoma after curative. 5. Xiao C, Hai-Peng, Mei L, Liang Q.Advances in non-surgical management of primary liver cancer. Wld J Gastroenterol 2014 November 28; 20(44): B-13

70 Cancer of the Colon Treatment Guideline KMHK 初訂日期 :97 年 1 月 1 日 修訂日期 :107 年 7 月 10 日

71 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 f 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 Stage III 門診第一線用藥準則 (1): 5FU 500 mg/m 2 + Leucvin 100mg/ m 2 Weekly f 6 of 8 weeks 改 Weekly f 6 of 8 weeks2-3 cycle (4)High Risk Stage II 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 posteri local excision + post-op radiotherapy and chemotheraopy 刪除 chemotheraopy 新增 LAR 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 APR (8) 直腸癌 Stage B3, C3 T4 N0-2 M0 治療準則 Pre-op chemotherapy + radiotherapy, then AP low anteri resection ± intraoperative brachytherapy 改 Pre-op chemotherapy + radiotherapy, then OP low anteri resection ±then RT (1) 修訂 Pedunculated Sessile polyp(adenoma [tubular, Tubulovillous, Villous]) with Invasive cancer 治療準則 (2) 修訂 Colon cancer Appropriate f Resection(non- metastatic) 治療準則 C-3 C-4 C-6 C-7 C-11 C-12 C-12 C-14 C-6 C

72 (3) 修訂 Patient appropriate f intensive therapy (metastasis) 治療準則 C-10~ 年 (1) 修訂 Pedunculated Sessile polyp(adenoma [tubular, Tubulovillous, Villous]) with C Invasive cancer 治療準則 (2) 修訂 Suspected proven metastatic adeno- carcinoma fm large bowel (Duke`s D stage C-3 IV) 治療準則 C-4 (3) 修訂 Colon cancer Appropriate f Resection(non- metastatic) 治療準則 C-5 (4) 修訂大腸癌 MONITORING/SURVEILANCE Abdominal CT sonography 2 years: Q6m 改 Q3-6m C-6 (5) 修訂直腸癌 MONITORING/SURVEILANCE Pelvis CT/MRI sonography 2 years: Q6m 改 Q3-6m C-8 (6) 修訂結腸癌第四期合併肝轉移追蹤準則 C-9~10 (7) 修訂結腸癌 (Adjuvant therapy) 治療準則 C-12~13 (8) 修訂 Patient appropriate f intensive therapy (metastasis) 治療準則 C-14 (9) 修訂 Rectal Cancer T3 N0 M0(high risk),t1-3 N1-2 M0 治療準則 (10) 修訂 Rectal Cancer stage B3,C3 T4N0-2M0 stage D Any T and N M1 治療準則 104 年 (1) 增訂大腸直腸癌目的 參考文件 範圍 定義 內容 C (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 文獻查證 C-18~ 年 (1) 修訂大腸直腸癌治療準則 年 7 月 21 日 (1) 增訂 colon cancer colectomy with en bloc removal of regional lymph node Observe C (2) 刪除 colon cancer wkup PET-CT scan 核子醫學須轉至高醫 C-4 增加 colon cancer surgery colostomy C-5 C-7 C-11 (3) 增加 colon cancer treatment FOLFIRI ±Panitumumab cetuximab C-8

73 C-9 (4) 增加 colon cancer therapy after second progression 可用 Stivarga C-14 (5) 增加 rectum cancer findings fragmented specimen margin cannot be assessed unfavable histological C-17 features 可 operation 或 observe (6) 刪除 rectal cancer patients with medical contraindication to combined modality therapy C-20 (7) 刪除 primary treatment 5-FU/RT 或轉介高醫 C-22 (8) 刪除 rectal cancer resectable 後續 wkup C-24 (9) 增加 rectal cancer therapy after second progression 可用 Stivarga C-25 (10) 增加大腸直腸癌化療藥物 Vectibix Stivarga Ziv-aflibercept C 年 7 月 10 日 (1) 增加 4.14 RAS 基因突變測試 (RAS test):ras 基因突變也可以評估轉移性結大腸直腸癌 (mcrc) 患者 C-2 對 EGFR 標靶治療的主要預測因子之一 (2) 增加 T3, N0, M0 (no high risk features) 治療藥物 UFUR C-5 (3) 刪除 Neoadjuvant therapy (f 2-3 months) C-7,C-23 (4) 增加 FOLFIRI ± (bevacizumab ziv-aflibercept ramucirumab ) C-11,C-24,C-25 (5) 刪除 Irinotecan ± (bevacizumab ziv-aflibercept ) C-11,C-24,C-25 (6) 刪除 Irinotecan + (cetuximab panitumumab) [RAS WT only] C-12,C-25 (7) 更新 AJCC 分期為 8TH C-28 (8) 更新參考文獻 National Comprehensive Cancer Netwk. Clinical Practice Guideline in Oncology: Colon C-31 Cancers V (9) 更新參考文獻 National Comprehensive Cancer Netwk. Clinical Practice Guideline in Oncology: Rectal C-31 Cancers V

74 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. 定義 : 泛指臨床科醫療人員皆可參考適用 4. 內容 : 4.1. 大腸直腸癌診斷及評估 4.2. 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 4.3. 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 4.4. 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 4.5. 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 4.6. 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 4.7. 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 4.8. 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 4.9. 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 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 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 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 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 C-1

75 4.14. RAS 基因突變測試 (RAS test):ras 基因突變也可以評估轉移性結大腸直腸癌 (mcrc) 患者對 EGFR 標靶治療的主要預測因子之一 *intraoperative radiation therapy(iort),if available, should be considered f patients with T4 recurrent cancers as an additional boost. C-2

76 Cancer of the Colon Treatment Guideline 結腸癌治療準則 Clinical presentation wkup findings surgery Pedunculated sessile polyp (adenoma) with invasion cancer Pathology review Colonoscopy Marking of cancerous polyp site (at time of colonoscopy within 2 wks) Single specimen completely removed with favable histological features and clear margins Fragmented specimen margin cannot be assessed unfavable histological features Pedunculated polyp with invasive cancer Senssile polyp with invasive cancer Observe Observe ( 告知觀察, 有較高機會復發或轉移 ) Radical colectomy Radical colectomy Observe See pathologic stage adjuvant therapy(c-5) and surveillance(c-9) C-3

77 Cancer of the Colon Treatment Guideline 結腸癌治療準則 Clinical presentation wkup findings surgery Resectable Non-obstructing Radical colectomy Colon cancer Appropriate f resection (non-metastatic) Colonoscopy CBC,chemistry profile,cea Chest X-ray Abdominal pelvic CT Resectable obstructing Radical colectomy radical colectomy with diversion Diversion colostomy Radical colectomy See pathologic stage adjuvant therapy (C-5) and surveillance (C-11) Locally unresectable medically inoperable Discuss with patient, may consider systemic therapy (C-12,C-13) C-4

78 Cancer of the Colon Treatment Guideline 結腸癌治療準則 Pathologic stase Adjuvant treatment Tis; T1, N0, M0 T2, N0, M0 Observation See Surveillance(C-9) T3, N0, M0 (no high risk features) Observation UFUR 5-FU/leucovin Capecitabine See Surveillance(C-9) T3, N0, M0 with high risk f systemic recurrence T4, N0, M0 UFUR Capecitabine. 5-FU/leucovin FOLFOX XELOX Observation See Surveillance(C-9) T any,n1-2,m0 FOLFOX XELOX Capecitabine 5-FU/leucovin UFUR See Surveillance(C-9) C-5

79 Cancer of the Colon Treatment Guideline 結腸癌治療準則 Clinical presentation Wkup Findings Suspected proven metastatic synchronous adenocarcinoma from large bowel (Any T, any N,M1) colonoscopy chest X-ray abdominal/pelvic CT CBC, chemistry profile Determination of RAS gene status Multidisciplinary team evaluation including a surgeon experienced in the resection of hepatobiliary and lung metastases Synchronous liver only and/ lung only metastases Synchronous abdominal/peritoneal metastases Resectable potential resectable (C-7) See Treament (C-8) Synchronous unresectable metastases See Systemic Therapy (C-15,C-16) C-6

80 Cancer of the Colon Treatment Guideline 結腸癌治療準則 Treatment Therapy after resection Synchronous staged colectomy with liver lung resection Neoadjuvant therapy FOLFOX XELOX FOLFIRI ±bevacizumab FOLFIRI FOLFOX ± panitumumab cetuximab [RAS WT only] followed by synchronous staged colectomy and resection of metastatic disease Colectomy, followed by chemotherapy FOLFOX XELOX FOLFIRI ±bevacizumab FOLFIRI FOLFOX ± panitumumab cetuximab [RAS WT only]and staged resection of metastatic disease FOLFOX XELOX FOLFIRI ± bevacizumab FOLFIRI FOLFOX ± panitumumab cetuximab [RAS WT only] See Surveillance (C-9) C-7

81 Cancer of the Colon Treatment Guideline 結腸癌治療準則 Finding Primary treatment Nonobstructing See Systemic Therapy (C-15,C-16) Synchronous abdominal/ Peritoneal merastases Obstructing Colon resection Diverting colostomy Bypass surgery See Systemic Therapy (C-15,C-16) C-8

82 Cancer of the Colon Treatment Guideline 結腸癌治療準則 surveillance StageⅠ, II, III Histy and physical every 3-6 mo f 2 y, then every 6 mo f a total of 5 y CEA every 3-6 mo f 2 y, then every 6 mo f a total of 5 y Chest/abdominal/pelvic CT every 6-12 mo f a total of 5 y Colonoscopy in 1 y except if no preoperative colonoscopy due to obstructing lesion, colonoscopy in 3-6 mo Serial CEA elevation documented recurrence Stage IV Histy and physical every 3-6 mo f 2 y, then every 6 mo f a total of 5 y CEA every 3-6 mo x 2 y, then every 6 mo x 3-5 y Chest/abdominal/pelvic CT scan every 3-6 mo x 2 y, then every 6-12 mo f a total of 5 y Colonoscopy in 1 y except if no preoperative colonoscopy due to obstructing lesion, colonoscopy in 3-6 mo C-9

83 Cancer of the Colon Treatment Guideline 結腸癌治療準則 Recurrence wkup Serial CEA elevation physical exam colonoscopy chest/abdominal/ pelvic CT Abdominal echo bone scan if necessary Negative findings Conside PET-CT Scan 轉介高醫檢查 Negative findings Positive findings See treatment f documented metastases, below Documented metastases by CT, MRI, PET Resectable Unresectable See Systemic Therapy (C-15,C-16) Observation See Systemic Therapy (C-15,C-16) C-10

84 Cancer of the Colon Treatment Guideline 結腸癌治療準則 Unresectable metastases Primary treatment Previous adjuvant FOLFOX within 6-12 months Previous adjuvant FOLFOX me then 6-12 months Previous 5-FU/LV capecitabine NO previous chemotherapy FOLFIRI±Bevacizumab ziv-aflibercept ramucirumab FOLFIRI±panitumumab cetuximab [RAS WT only] See Systemic Therapy (C-15,C-16) Re-evaluate f conversion to resectable every 2-3 mo Resection Converted to resectable Remains unresectable See Systemic Therapy(C-15,C-16) Observation See Systemic Therapy(C-15,C-16) C-11

85 Cancer of the Colon Treatment Guideline 結腸癌治療準則 Systemic treatment Initial therapy Subsequent Therapy Therapy after second progression FOLFOX±Bevacizumab XELOX±Bevacizumab FOLFOX+panitumumab cetuximab [RAS WT only] FOLFIRI ± (bevacizumab ziv-aflibercept ramucirumab ) FOLFIRI + (cetuximab panitumumab) [RAS WT only] Regafenib Best supptive care Patient Appropriate F Intensive therapy FOLFIRI±Bevacizumab FOLFIRI+ panitumumab cetuximab [RAS WT only] FOLFOX ± bevacizumab XELOX ± bevacizumab Regafenib Best supptive care 5-FU/leucovin Capecitabine± Bevacizumab FOLFOX ± Bevacizumab XELOX ± Bevacizumab Regafenib Best supptive care FOLFIRI ± (bevacizumab ziv-aflibercept ramucirumab) FOLFOX XELOX Regafenib Best supptive care FOLFOXIRI± Bevacizumab Regafenib Best supptive care C-12

86 Cancer of the Colon Treatment Guideline 結腸癌治療準則 Systemic treatment Initial therapy Therapy after first progression Patients not appropriate f intensive therapy Infusional 5-FU + leucovin ±bevacizumab Capecitabine ± bevacizumab (Cetuximab panitumumab) [RAS WT only] Improvement in function status No improvement in function status Consider initial therapy as above Best supptive care C-13

87 Cancer of the Rectum Treatment Guideline KMHK 初訂日期 :97 年 1 月 1 日修訂日期 :107 年 7 月 10 日 C-14

88 Cancer of the Rectum Treatment Guideline 直腸癌治療準則 Clinical presentation Wkup Findings Pedunculated polyp with invasive cancer Observe Pedunculated polyp sessile polyp(adenoma) with invasive cancer Pathology review Colonscopy Marking of cancerous polyp site(at time of colonscopy within 2 wks if deemed necessary by the surgeon) Single specimen, completely removed with favable histological feature and clear margins Fragmented specimen margin cannot be assessed unfavable histological features Sessile polyp with invasive cancer Transanal excision if appropriate Transabdominal resection Observe ( 會告知僅觀察有較高機會復發或轉移 ) Observe ( 會告知僅觀察有較高機會復發或轉移 ) Transanal excision if appropriate Transabdominal resection C-15

89 Cancer of the Rectum Treatment Guideline 直腸癌治療準則 Clinical presentation Wkup Clinical stage T1-2, N0 (C-17) Rectal cancer appropriate f resection Biopsy Pathology review Chest X-ray Colonscopy Abdominal/pelvic CT MRI CEA Colonoscopy marking if small tum T3, N0 (C-18) T any, N1-2 (C-18) T4 and/ locally unresectable (C-18) T any, N any, M1 Resectable metastases (C-19) Suspected proven metastatic adenocarcinoma See management of suspected proven metastatic synchronous adenocarcinoma (C-20) C-16

90 Cancer of the Rectum Treatment Guideline 直腸癌治療準則 Clinical primary treatment stage Adjuvant treatment (6mo perioperative treatment preferred) ct1,n0 Transanal local Excision, if Appropriate T1,Nx; Margins negative T1Nx,margin involve T1,Nx;with high risk feature T2,Nx Observe RT Trans-abdominal resection pt1-2, N0, M0 pt4,n0,m0 pt1-4,n1-2,m0 Observe 5FU ± Leucovin FOLFOX Capecitabine ± oxaliplatin, then infusion 5FU/RT bolus 5FU/ Leucovin/RT Capecitabine/ RT, then 5FU± Leucovin FOLFOX Capecitabine ± oxaliplatin Continuous 5FU/RT bolus 5FU/ Leucovin/RT Capecitabine/ RT follow by 5FU ± Leucovin FOLFOX Capecitabine ± oxaliplatin pt1-2, N0, M0 Observe pt3, N0,M0 6mo Continuous 5FU ± Leucovin UFUR FOLFOX Capecitabine ± oxaliplatin ct1-2,n0 Trans-abdominal resection pt4,n0,m0 pt1-4,n1-2,m0 5FU ± Leucovin FOLFOX Capecitabine ± oxaliplatin, then infusion 5FU/RT, bolus 5FU/ Leucovin/RT Capecitabine/ RT, then 5FU± Leucovin FOLFOX Capecitabine ± oxaliplatin Continuous 5FU/RT bolus 5FU/ Leucovin/RT Capecitabine/ RT follow by 5FU±Leucovin FOLFOX Capecitabine ± oxaliplatin pt3, N0,M0 6mo Continuous 5FU ± Leucovin UFUR FOLFOX Capecitabine ± oxaliplatin C-17

91 Cancer of the Rectum Treatment Guideline 直腸癌治療準則 Clinical stage Primary treatment Adjuvant treatment (6mo perioperative treatment preferred) T3, N0, M0 T any,n1-2 Preoperation infusional 5FU/RT Capecitabine/RT bolus 5FU/ Leucovin/RT Transabdominal resection pt1-2,n0,m0 Transabdominal resection Observe 5FU±Leucovin FOLFOX Capecitabine ± oxaliplatin pt3,n0,m0 pt1-3,n1-2 Reconsider: 5FU ± Leucovin FOLFOX Capecitabine ± oxaliplatin, infusion 5FU/RT, bolus 5FU/ Leucovin/RT Capecitabine/ RT, then 5FU ± Leucovin FOLFOX Capecitabine ± oxaliplatin T4 and/ Locally unresectable Infusion IV 5FU/RT bolus 5FU/ Leucovin/RT Capecitabine/RT UFUR/RT Resection, if possible Any T 5FU ± Leucovin FOLFOX Capecitabine ± oxaliplatin C-18

92 Cancer of the Rectum Treatment Guideline 直腸癌治療準則 Clinical stage Primary treatment Adjuvant treatment (6mo perioperative treatment preferred) T any, N any, M1 Resectable synchronous metastatic Combination chemotherapy (FOLFIRI FOLFOX XELOX) ± bevacizumab FOLFIRI ± (cetuximab panitumumab) [RAS WT only] Staged synchronous resection of metastases+ rectal lesion pt1-2,n0,m1 pt3, any N, M1 any T, N1-2, M1 Stage synchronous resection of metastases + rectal lesion Infusion IV 5FU pelvic RT bolus 5FU+leucovin/Pelvic RT capecitabine/rt See Systemic Therapy(C-25, C-26) Consider infusion IV 5-FU/Pelvic RT bolus 5-Fu + leucovin/pelvic RT capecitabine/rt 5-FU ± leucovin FOLFOX capecitabine ± oxaliplatin,then infusional 5-FU/RT bolus 5-FU/leucovin/RT, then 5-FU ± leucovin FOLFOX capecitabine ± oxaliplatin Infusional IV 5-FU/pelvic RT bolus 5-FU/leucovin/pelvic RT capecitabine/rt Staged synchronous resection of metastases +rectal lesion See Systemic Therapy(C-25, C-26) C-19

93 Cancer of the Rectum Treatment Guideline 直腸癌治療準則 Clinical stage Primary treatment ct Any, N Any, M1 Unresetable synchronous metastases Medically inoperable Symptomatic Combination systemic chemotherapy (C-25, C-26) Resection of involved rectal segment Diverting colostomy Asymptomatic See Systemic Therapy(C-25, C-26) Reassess response to derermine resectabilty C-20

94 Cancer of the Rectum Treatment Guideline 直腸癌治療準則 Stage I, II, III Histy and physical every 3 6 mo f 2 y, then every 6 mo f a total of 5 y CEA every 3 6 mo f 2 y, then every 6 mo f a total of 5 y Chest/abdominal/pelvic CT every 6 12 mo (categy 2B f frequency <12 mo) f a total of 5 y Colonoscopy in 1 y except if no preoperative colonoscopy due to obstructing lesion, colonoscopy in 3 6 mo Serial CEA elevation documented recurrence Stage IV Histy and physical every 3 6 mo f 2 y, then every 6 mo f a total of 5 y CEA every 3 6 mo x 2 y, then every 6 mo x 3 5 y Chest/abdominal/pelvic CT scan every 3 6 mo (categy 2B f frequency <6 mo) x 2 y, then every 6 12 mo f a total of 5 y Colonoscopy in 1 y except if no preoperative colonoscopy due to obstructing lesion, colonoscopy in 3 6 mo C-21

95 Cancer of the Rectum Treatment Guideline 直腸癌治療準則 Recurrence Wkup Treatment Serial CEA elevation Physical exam Colonoscopy Chest/abdominal/pelvic CT Consider PET-CT scan (PET-CT scan 須至高醫檢查 ) Negative findings Positive findings Consider PET-CT scan Reevaluate chest/abdominal/ pelvic CT in 3mo See treatment f lsolated pelvic/anastomotic recurrence documented metachronous, below Negative findings Positive findings See treatment f lsolated pelvic/anastomotic recurrence documented metachronous, below Isolated pelvic/ana stomotic recurrence Potentially resectable Resection Preoperative 5-FU+RT Chemotherapy + RT Resection ± IORT Chemotherapy+RT if not given previously Unresectable Chemotherapy+RT Resectable See primary treatment (C-23) Documented Metachronous Metastases by CT,MRI and/ biopsy Unresetable (potentially convertible unconvertible) See primary treatment (C-24) C-22

96 Cancer of the Rectum Treatment Guideline 直腸癌治療準則 Resectable metastases Primary treatment Resection See Systemic Therapy (C-25) Observation Neoajdvant chemotherapy Resectable No progression Repeat neoadjuvant chemotherapy FOLFOX Progression See Systemic Therapy(C-25) Observation *6-12 個月內有化學治療者, 無效換化療藥物 C-23

97 Cancer of the Rectum Treatment Guideline 直腸癌治療準則 Unresectable metastases Primary treatment Previous adjuvant FOLFOX within 6-12 months Previous adjuvant FOLFOX me then 6-12 months Previous 5-FU/LV capecitabine NO previous chemotherapy FOLFIRI±Bevacizumab ziv-aflibercept ramucirumab FOLFIRI±panitumumab cetuximab [RAS WT only] See Systemic Therapy (C-25,C-26) Re-evaluate f conversion to resectable every 2-3 mo Resection Converted to resectable Remains unresectable See Systemic Therapy(C-25,C-26) Observation See Systemic Therapy(C-25,C-26) C-24

98 Cancer of the Rectum Treatment Guideline 直腸癌治療準則 Systemic treatment Initial therapy Subsequent Therapy Therapy after second progression FOLFOX±Bevacizumab XELOX±Bevacizumab FOLFOX+panitumumab cetuximab [RAS WT only] FOLFIRI ± (bevacizumab ziv-aflibercept ramucirumab ) FOLFIRI + (cetuximab panitumumab) [RAS WT only] Regafenib Best supptive care Patient Appropriate F Intensive therapy FOLFIRI±Bevacizumab FOLFIRI+ panitumumab cetuximab [RAS WT only] FOLFOX ± bevacizumab XELOX ± bevacizumab Regafenib Best supptive care 5-FU/leucovin Capecitabine ± Bevacizumab FOLFOX ± Bevacizumab XELOX ± Bevacizumab Regafenib Best supptive care FOLFIRI ± (bevacizumab ziv-aflibercept ramucirumab) FOLFOX XELOX Regafenib Best supptive care FOLFOXIRI± Bevacizumab Regafenib Best supptive care C-25

99 Cancer of the Rectum Treatment Guideline 直腸癌治療準則 Systemic treatment Initial therapy Therapy after first progression Patients not appropriate f intensive therapy Infusional 5-FU + leucovin ±bevacizumab Capecitabine ± bevacizumab (Cetuximab panitumumab) [RAS WT only] Improvement in function status No improvement in function status Consider initial therapy as above Best supptive care C-26

100 SURVEILLANCE Pretreatment 2 years 2-5 years >5 years Physical exam, including DRE ˇ Q3-6m Q6-12m Q12m Stool occult blood test ˇ Q12m CBC ˇ Q3-6m Q6m Q12m CEA ˇ Q3-6m Q6m Q12m Chest X-ray ˇ Q6m Q6-12m Q12m Abdominal CT sonography (f colon cancer) Pelvis CT / MRI sonography (f rectal cancer) ˇ Q3-6m Q6-12m ˇ Q3-6m Q6-12m Colonscopy ˇ In 1 year In 3 year Q5Y C-27

101 AJCC 8th Table 1. Definitions f T, N, M T TX T0 Tis T1 T2 Primary Tum Primary tum cannot be assessed No evidence of primary tum Carcinoma in situ: intramucosal carcinoma (involvement of lamina propria with no extension through muscularis mucosae) Tum invades the submucosa (through the muscularis mucosa but not into the muscularis propria) Tum invades the muscularis propria T3 Tum invades through the muscularis propria into the pericolectal tissues T4 Tum invades the visceral peritoneum invades adheres to adjacent gan structure T4a Tum invades through the visceral peritoneum (including gross perfation of the bowel through tum and continuous invasion of tum through areas of inflammation to the surface of the visceral peritoneum) N NX N0 N1 N2 T4b Tum directly invades is adheres to adjacent gans structures N1a Regional Lymph Nodes Regional lymph nodes cannot be assessed No regional lymph node metastasis No regional lymph nodes are positive, but there are tum deposits in the subserosa, mesentery, nonperitonealized pericolic, perirectal/mesectal tissues One regional lymph node is positive N1b Two three regional lymph nodes are positive N1c No regional lymph nodes are positive, but there are tum deposits in the subserosa, mesentery, nonperitonealized pericolic, perirectal/ mesectal tissues N2a N2b Four me regional lymph nodes are positive Four to six regional lymph nodes are positive Seven me regional lymph nodes are ositive M Distant Metastasis M0 No distant metastasis by imaging, etc.; no evidence of tum in distant sites gans M1 Metastasis to one me distant sites gans peritoneal metastasis is identified M1a Metastasis to one site gan is identified without peritoneal metastasis M1b Metastasis to two me sites gans is identified without peritoneal metastasis M1c Metastasis to the peritoneal surface is identified alone with other site gan metastases Table 2. AJCC Prognostic Stage Groups T N M Stage 0 Tis N0 M0 Stage I T1-T2 N0 M0 Stage IIA T3 N0 M0 Stage IIB T4a N0 M0 Stage IIC T4b N0 M0 Stage IIIA T1-T2 N1/N1c M0 T1 N2a M0 Stage IIIB T3-T4a N1/N1c M0 T2-T3 N2a M0 T1-T2 N2b M0 Stage IIIC T4a N2a M0 T3-T4a N2b M0 T4b N1-N2 M Stage IVA Any T Any N M1a Stage IVB Any T Any N M1b Stage IVC Any T Any N M1c C-28

102 大腸直腸癌化療藥物 5-FU/leucovin-5-FU/LV (slv5fu2) UFUR Xeloda XELOX Leucovin 400mg/m2 in N/S 250ml Tegafur 200 mg PO BID. Capecitabine mg/m 2 PO BID Oxaliplatin 85 mg/m2 in 5%G/w IVD 2hrs Tegafur 100 mg PO TID. x 14 days, 7 days off Cycled every ml IVD 2hrs. 5-FU 400mg/m2 in N/S 250ml IVD 2hrs weeks Capecitabine mg/m2 PO 5-FU 2400mg/m2 in N/S 500ml IVD keep 46hrs BID x 14 days, 7 days off Repeat every 2 weeks. FOLFOX4 mfolfox6 FOLFIRI FOLFOXIRI Oxaliplatin 85 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Leucovin 200mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 (Oxaliplatin 和 Leucovin 同時滴 ) 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 5-FU 600mg/m 2 in N/S 500ml IVD 22hrs on Day 1 and Day 2 Oxaliplatin 85 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Leucovin 400mg/m 2 in N/S 250ml IVD 2hrs(Oxaliplatin 和 Leucovin 同時滴 ) 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs 5-FU 2400mg/m 2 in N/S 500ml IVD keep 46hrs Irinotecan 180 mg/m 2 IV in N/S 500 ml IVD 2hrs Leucovin 400mg/m 2 in N/S 250ml IVD 2hrs(Irinotecan 和 Leucovin 同時滴 ) 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs 5-FU 2400mg/m 2 in N/S 500ml IVD keep 46hrs Repeat every 2 weeks Irinotecan 165 mg/m 2 IV day 1, Oxaliplatin 85 mg/m 2 IV day 1, Leucovin 400mg/m 2 IV day 1, 5-FU 3200mg/m 2 IV over 48hrs. Continuous infusion startimg on day 1. cetuximab (KRAS/NRAS WT only) Cetuximab 400 mg/m2 IV over 2 hours first infusion, then 250 mg/m2 IV over 60 minutes weekly Cetuximab 500 mg/m2 IV over 2 hours, day 1, every 2 weeks ziv-aflibercept Ziv-aflibercept 4 mg/kg IV over 60 minutes, day 1 Repeat every 2 weeks panitumumab (KRAS/NRAS WT only) Panitumumab 6 mg/kg IV over 60 minutes, day 1 Repeat every 2 weeks bevacizumab Bevacizumab 5 mg/kg IV, day 1 Repeat every 2 weeks Regafenib Ramucirumab Regafenib 160 mg PO daily days 1 21 Repeat every 28 days Ramucirumab 8 mg/kg over 60 minutes, day 1 Repeated every 2 weeks C-29

103 Dosing Schedules f Concurrent Chemotherapy/RT RT + continuous infusion 5-FU RT + Capecitabine RT + 5-FU/leucovin RT + UFUR 5-FU 225 mg/m2 over 24 hours Capecitabine# 825 mg/m2 twice 5-FU 400 mg/m2 IV bolus + Tegafur 200 mg PO BID. 5 7 days/week during RT daily 5 d/wk + RT x 5 weeks leucovin 20 mg/m2 IV bolus during RT f 4 days during week 1 and 5 of RT C-30

104 參考文獻 1. National Comprehensive Cancer Netwk. Clinical Practice Guideline in Oncology: Colon Cancers V National Comprehensive Cancer Netwk. Clinical Practice Guideline in Oncology: Rectal Cancers V Hofheinz R, Wenz FK, Post S, et al. Chemadiotherapy with capecitabine versus fluouracil f locally advanced rectal cancer: A randomized, multicentre, noninferiity,phase 3 trial. Lancet Oncol 2012;13: 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: 5. TCOG 大腸癌工作群編撰小組 (2010) 大腸癌臨床診療指引 苗栗縣 國家衛生研究院 C-31

105 Cancer of the Gastric Treatment Guideline KMHK 初訂日期 :97 年 1 月 1 日 修訂日期 :107 年 7 月 10 日

106 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 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 ECF if received preoperatively Chemadiation ( Fluopyrimidine-based) f selected patients 改 UFUR follow C up (2)T3,T4 Any T,N+ 治療 ECF if received preoperatively RT, Gy + concurrent C-15 5-FU-based radiosensitization + 5-FU ± leucovin 改 Adjuvant Chemotherapy(ECF EOX FOLFOX4 Xeloda UFUR TS1) 103 年 (1) 因本院沒有再做 Laparoscopic staging 故 Wkup 診斷為 Locegional ( M0 ) 之後 Multidisciplinary Evaluation C-22 C C 年 (1) 增訂目的 參考文件 範圍 定義 內容 C 年 (1) 增訂胃癌簡易版治療準則 Stage 3 Stage 4 C-37-C (2) 修訂胃癌診療指引共識 106 年 7 月 21 日 (1) 修訂 Gastric cancer primary treament Locegional disease 需同時接受 platinum-based C 類的 Chemotherapy C-43 (2) 新增標靶藥物 Ramucirumab (CYRAMZAR) 是種 anti-veegfr2 藥物 ( 血管內皮生長 C-35 因子接受器第二型拮抗劑 ) 可合併紫杉醇 Paclitaxel 使用

107 107 年 7 月 10 日 (1) 更新 AJCC 分期為 8th (2) 更新參考文獻 National Comprehensive Cancer Netwk. Clinical Practice Guideline in Oncology: Gastric Cancers V C-43,C-44 C

108 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. 定義 : 3.1 權責 : 臨床科學相關科系醫療人員 3.2 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 3.3 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 4. 內容 : C-34

109 4.1 胃癌簡易版治療準則 AJCC/ 治療 OP C/T R/T Target Hospice Stage 0 Stage 1 ESD ( 轉高醫 ) EMR Gastrectomy ESD ( 轉高醫 ) EMR Gastrectomy Stage 2 Gastrectomy Preoperative Chemotherapy: 1. Fluouracil+ Cisplatin 2. Cisplatin+Capecitabine( 口服 ) 3. Oxalipltin+Capecitabine( 口服 ) 4. Oxalipltin+Fluouracil+Leucovin 5. TS-1(Tegafur/gimeracil/oteracil) ( 排除 T1 ) Stage 3 Gastrectomy Preoperative Chemotherapy: 1. Fluouracil+ Cisplatin 2. Cisplatin+Capecitabine( 口服 ) 3. Oxalipltin+Capecitabine( 口服 ) 4. Oxalipltin+Fluouracil+Leucovin 5. TS-1(Tegafur/gimeracil/oteracil) IIIA 或 IIIB Stage 4 Gastrectomy 1. Fluouracil+ Cisplatin 2. Epirubicin+Cisplatin+Xeloda( 口服 ) 3. Epirubicin+Oxaliplatin+Xeloda( 口服 ) 4. Epirubicin+Oxaliplatin+Fluouracil 5. Oxalipltin+Fluouracil+Leucovin CCRT CCRT Trastuzumab Ramucirumab Symptomatic care C-35

110 Cancer of the Gastric Treatment Guideline 胃癌治療準則 WORKUP CLINICAL STAGE ADDITIONAL EVALUATION H&P Upper GI endoscopy and biopsy Chest /abdomen/pelvic CT with ctis ct1a Medically fit Non-surgical candidate al and IV contrast PET-CT evaluation(if need) CBC and comprehensive Medically fit, potentially resectable Multidisciplinary review preferred See C-37 chemistry profile Endoscopic ultrasound (EUS) if no evidence of M1 disease(optional 轉介高醫執行 ) Locegional (cm0) Surgically unresectable Consider laparoscopy with cytology Biopsy of metastatic disease (if clinically indicated) H.pyli test Non-surgical candidate Stage IV (cm1) Palliative Management (see C-42) C-36

111 Cancer of the Gastric Treatment Guideline 胃癌治療準則 CONCLUSIONS OF MULTIDISCIPLINARY FINAL STAGE h PRIMARY TREATMENT ctis ct1a Non-surgical candidate Medically fit Medically fit, potentially resectable ct1b ct2 higher, Any N ER ER Surgery Surgery Surgery Perioperative chemotherapy Preoperative chemadiation Surgery Endoscopic surveillance Surgical Outcomes F Patients Who Have Not Received Preoperative Therapy (see C-38) Surgical Outcomes F Patients Who Have Received Preoperative Therapy (see C-39) Locegional disease (cm0) Surgically, unresectable Chemadiation Systemic therapy Palliative Management (see C-42) Post-Treatment Assessment/ Additional Management (see C-40) Non-surgical candidate Chemadiation (Definitive) Palliative Management (see C-42) Post-Treatment Assessment/ Additional Management (see C-40) Metastatic disease (cm1) Palliative Management (see C-42) C-37

112 Cancer of the Gastric Treatment Guideline 胃癌治療準則 SURGICAL OUTCOMES/CLINICAL PATHOLOGIC FINDINGS (Patients Have Not Received Preoperative Chemotherapy Chemadiation) R0 resection p TUMOR CLASSIFICATION ptis pt1, N0 pt2, N0 POSTOPERATIVE MANAGEMENT Surveillance Surveillance Chemotherapy (fluopyrimidine-based) ± RT pt3, pt4, Any N Any pt, N+ Chemotherapy (fluopyrimidine-based) ± RT (FOLFOX4 XELOX Xeloda UFUR TS1) Follow-up (see C-41) R1 resection Chemotherapy (fluopyrimidine-based) ± RT R2 resection pm1 Chemotherapy (fluopyrimidine-based) ± RT Palliative Management (see C-42),as clinically indicated Palliative Management (see C-42) C-38 * 放射線治療需轉介

113 Cancer of the Gastric Treatment Guideline 胃癌治療準則 SURGICAL OUTCOMES/CLINICAL TUMOR POSTOPERATIVE MANAGEMENT PATHOLOGIC FINDINGS CLASSIFICATION h (Patients Have Received Preoperative Chemotherapy Chemadiation) Node negative Observation until progression R0 resection (yp Any T, N0) (if received preoperative chemadiation) Node positive (yp Any T, N+) Chemotherapy If received preoperatively Follow-up R1 resection Chemadiation (fluopyrimidine-based), only if not received preoperatively Chemotherapy,if received preoperatively Consider re-resection (see C-41) R2 resection Chemadiation (fluopyrimidine-based) only if not received preoperatively Palliative Management (see C-42), as clinically indicated ypm1 Palliative Management (see C-42) C-39 * 放射線治療需轉介

114 Cancer of the Gastric Treatment Guideline 胃癌治療準則 POST-TREATMENT ASSESSMENT OUTCOME ADDITIONAL MANAGEMENT Unresectable disease Non-surgical candidate j following primary treatment Restaging : Chest/abdomen/pelvic CT with al and IV contrast CBC and comprehensive chemistry Profile PET/CT scan as clinically indicated Resectable and medically operable Unresectable Medically inoperable and/ Metastatic disease Surgery (preferred), if appropriate Follow-up (see C-41) Palliative Management (see C-42) C-40

115 Cancer of the Gastric Treatment Guideline 胃癌治療準則 FOLLOW-UP/SURVEILLANCE RECURRENCE H&P every 3-6 mo f 1-2y, every 6-12 mo f 3-5y, then annually CBC and chemistry Profile as indicated Abdominal CT with contrast upper GI endoscopy, as clinically indicated Monit f nutritional deficiency (eg, B 12 and iron) in surgically resected patients and treat as indicated Locegional recurrence Metastatic disease Resectable and medically operable Unresectable medically inoperable Consider surgery Palliative Management (seec-42) See Palliative Management (see C-42) See Palliative Management (see C-42) C-41

116 Cancer of the Gastric Treatment Guideline 胃癌治療準則 PERFORMANCE STATUS PALLIATIVE MANAGEMENT Karnofsky perfmance sce 60% ECOG perfmance sce 2 Systemic therapy n Palliative/Best supptive care t Unresectable locally advanced, Locally recurrent metastatic disease Karnofsky perfmance sce<60% ECOG perfmance sce 3 Palliative/Best supptive care t C-42

117 American Joint Committee on Cancer (AJCC) TNM Staging Classification f Carcinoma of the Stomach (8th ed., 2017) Definition of Primary Tum (T) ***Intramural extension to the duodenum esophagus is not considered invasion of an adjacent structure, but is classifi ed using the depth of the greatest invasion in any of these sites. T Categy TX T0 Tis T1 T1a T1b T2 T3 T4 T4a T4b T Criteria Primary tum cannot be assessed No evidence of primary tum Carcinoma in situ: intraepithelial tum without invasion of the lamina propria, high-grade dysplasia Tum invades the lamina propria, muscularis mucosae, submucosa Tum invades the lamina propria muscularis mucosae Tum invades the submucosa Tum invades the muscularis propria* Tum penetrates the subserosal connective tissue without invasion of the visceral peritoneum adjacent structures**, *** Tum invades the serosa (visceral peritoneum) adjacent structures**, *** Tum invades the serosa (visceral peritoneum) Tum invades adjacent structures/gans Definition of Regional Lymph Node (N) N Categy N Criteria NX Regional lymph node(s) cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in one two regional lymph nodes N2 Metastasis in three to six regional lymph nodes N3 Metastasis in seven me regional lymph nodes N3a Metastasis in seven to 15 regional lymph nodes N3b Metastasis in 16 me regional lymph nodes Definition of Distant Metastasis (M) M Categy M Criteria M0 No distant metastasis M1 Distant metastasis *A tum may penetrate the muscularis propria with extension into the gastrocolic gastrohepatic ligaments, into the greater lesser omentum, without perfation of Definitions of Histologic Grade (G) the visceral peritoneum covering these structures. In this case, the tum is classified as T3. If there is perfation of the visceral peritoneum covering the gastric ligaments the omentum, the tum should be classifi ed as T4. **The adjacent structures of the stomach include the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, and retroperitoneum. G GX G1 G2 G3 G Definition Grade cannot be assessed Well differentiated Moderately differentiated Poly differentiated, undifferentiated C-43

118 Clinical Staging (ctnm) ct cn M Stage 0 Tis N0 M0 Stage I T1 N0 M0 T2 N0 M0 Stage IIA T1 N1, N2, N3 M0 T2 N1, N2, N3 M0 Stage IIB T3 N0 M0 T4a N0 M0 Stage III T3 N1, N2, N3 M0 T4a N1, N2, N3 M0 Stage IVA T4b Any N M0 Stage IVB Any T Any N M1 Pathological (ptnm) pt pn M Stage 0 Tis N0 M0 Stage IA T1 N0 M0 Stage IB T1 N1 M0 T2 N0 M0 Stage IIA T1 N2 M0 T2 N1 M0 T3 N0 M0 Stage IIB T1 N3a M0 T2 N2 M0 T3 N1 M0 T4a N0 M0 Stage IIIA T2 N3a M0 T3 N2 M0 T4a N1 N2 M0 T4b N0 M0 Stage IIIB T1 N3b M0 T2 N3b M0 T3 N3a M0 T4a N3a M0 T4b N1 N2 M0 Stage IIIC T3 N3b M0 T4a N3b M0 T4b N3a N3b M0 Stage IV Any T Any N M1 Post Neoadjuvant Therapy (yptnm) yp T yp N M Stage I T1 N0 M0 T2 N0 M0 T1 N1 M0 Stage II T3 N0 M0 T2 N1 M0 T1 N2 M0 T4a N0 M0 T3 N1 M0 T2 N2 M0 T1 N3 M0 Stage III T4a N1 M0 T3 N2 M0 T2 N3 M0 T4b N0 M0 T4b N1 M0 T4a N2 M0 T3 N3 M0 T4b N2 M0 T4b N3 M0 T4a N3 M0 Stage IV Any T Any N M1 C-44

119 參考文獻 1. National Comprehensive Cancer Netwk. Clinical Practice Guideline in Oncology: Gastric Cancers V Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone f treatment of HER2-positive advanced gastric gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010;376: 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 C-45

120 Cancer of the Breast Treatment Guideline KMHK 初訂日期 :97 年 1 月 1 日 修訂日期 :107 年 7 月 20 日

121 乳癌修訂紀錄 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 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 1. 修訂 Lobular carcinoma in situ 流程圖 D invasive breast cancer wkup 新增 FDG PET/CT(optional f T3,N1,M0) 項目 3. 新增 principles of radiation therapy 說明 4. 修改 systemic adjuvant treatment hmone recept positive HER2 negative disease 流程圖 5. 修改 treatment of recurrent stage IV disease 流程圖 6. 刪除 follow-up therapy f hmone treatment of recurrence / stage IV disease 中 no response to hmonal therapy 打 chemotherapy 的流程圖 7. 新增 principles of HER-2 testing 流程圖 D-4 D-10 D-13 D-23 D-26 D 年 8. 刪除 pagets disease 流程圖 1. 刪除 margin status in DCIS 說明圖 2. 刪除 principles of breast reconstruction following mastectomy principles of radiation therapy 說明圖 3. 刪除 systemic adjuvant treatment favable histologies 圖表 4. 刪除 principles of HER-2 testing 圖 5. 新增 surgical axillary staging - stagei,iia,iib,iiia T3,N1, M0 圖表 刪除 summary of adjuvant therapy 圖表 7. 修改 adjuvant endocrine therapy 之流程圖 D-20

122 乳癌修訂紀錄 修訂日期 修訂內容摘要 修訂頁次 版本 8. 刪除 AJCC TNM staging 圖表 103 年 1. 修訂 Ductal carcinoma in situ 診斷治療流程圖,DCIS 不分腫瘤大小, 後續治療方法皆相同 D 修訂 Invasive breast cancer stage I, IIA, IIB, IIIA 之評估方法需檢驗 alkaline phosphatase D-2 3. 修訂 Invasive breast cancer-hmone recept positive, Her2 negative 治療流程圖, 增加若病理分期為 pn0 或 pn1mi 且腫瘤 >0.5cm 之後續治療 D-3 4. 修訂 Invasive breast cancer 之 preoperative chemotherapy guideline,stage IIA, IIB, IIIA 之評估方法可檢驗 alkaline phosphatase D 年 1. 修訂 Invasive breast cancer 之 systemic treatment of recurrent stage Ⅳ- ER and PR negative, ER and/ PR positive and endocrine refracty; HER2 negative and ER and PR negative; HER2 positive 之治療流程圖 D 年 4. 修訂 Invasive breast cancer-adjuvant endocrine therapy 之治療流程圖 1. (optional f stage I, lla llb, indicated if elevated alkaline phosphatase, abnmal LFTs, if T3, N1, M0) 改為 (optional f stage I, lla llb ⅢA, indicated if elevated alkaline phosphatase, abnmal LFTs, if T3, N1, M0) 2. FDG PET/CT (optional f T3, N1,M0)(categy2B) 刪除 D18 D 年 1. 修訂 Invasive breast cancer:systemic Treatment of Recurrent Stage IV Disease ER and PR negative, ER and/ PR positive and endocrine refracty; HER2 negative 建議直接行 chemotherapy±avastin 2.Invasive breast cancer: ER and PR negative; HER2 positive 建議直接行 Trastuzumab ±Chemotherapy Trastuzumab+ Pertuzumab+ Chemotherapy D3 D18 7.0

123 乳癌修訂紀錄 修訂日期 修訂內容摘要 修訂頁次 版本 107 年 1. 頁碼及參考文獻修訂 2.Invasive Breast Cancer: WORKUP (1)Abdominal CT US MRI (optional)(indicated if elevated alkaline phosphatase, abnmal LFTs, 新增 abnmal symptoms, abnmal physical exam of the abdomen (2) 新增 *Chest CT (optional)(if pulmonary symptoms present) 3.Invasive Breast Cancer: RT to whole breast with without boost to tum bed consideration of, 新增 accelerated partial breast Irradiation (APBI) 4.Invasive Breast Cancer: (1)Negative axillary nodes and tum 5 cm and axillary margins close(<1mm) 修訂為 Negative axillary nodes and tum 5 cm and negative margins but < 1mm (2)Margins positive 新增 Re-excision to negative margin is preferred. If not feasible, then post C/T strongly consider RT to chest wall ± infraclavicular ± supraclavicular area ± internal mammary nodes. 5.Invasive Breast Cancer: Node (+) (one me metastasis > 2 mm to one me ipsilateral axillary lymph nodes) Adjuvant ebdocrine therapy + adjuvant chemotherapy with trastuzumab 修訂為 Adjuvant ebdocrine therapy + adjuvant C/T pertuzumab with trastuzumab 6.Invasive Breast Cancer: pn1mi Consider adjuvant endocrine therapy 修訂為 Adjuvant endocrine therapy± adjuvant C/T 7.Invasive Breast Cancer: (1)pN0 pn1mi Tum cm, Tum > 1 cm 後方合併成一格, 修訂為 Consider adjuvant C/T with trastuzumab (2)Node (+) (one me metastasis > 2 mm to one me ipsilateral axillary lymph nodes) Adjuvant C/T with trastuzumab 修訂為 Adjuvant C/T with trastuzumab+ BINV-1 BINV-2 BINV-3 BINV-4 BINV-5 BINV pertuzumab BINV-8 8.Invasive Breast Cancer: Wkup 新增 *Chest CT(optional) BINV-10

124 乳癌修訂紀錄 修訂日期 修訂內容摘要 修訂頁次 版本 9.Invasive Breast Cancer: Adjuvant Treatment 新增 2.If HER2 (+) complete up to one year of HER2 targeted therapy with trastuzumab ± pretuzumab, maybe administered concurrently with RT and with endocrine therapy if indicated. 10.Invasive Breast Cancer: Wkup 新增 *Chest CT(optional) 11.Invasive Breast Cancer: (Adjuvant Treatment 分成兩部分, 分別為 Additional C/T + endocrine therapy if ER(+) and/ PR(+) complete up to one year of trastuzumab ± pertuzumab therapy if HER2(+) 12.Invasive Breast Cancer: Recurrence Wkup Initial Wkup Stage IV Disease 修訂為 Recurrence / Stage IV Disease Wkup 13.Invasive Breast Cancer: (1) Pri endocrine therapy within 1y 新增 Non visceral crisis C/T Hmone ±CDK4/6 inhibit (2) No pri endocrine therapy within 1y 新增 Non visceral crisis Hmone ± Herceptin C/T+Herceptin 14.Invasive Breast Cancer: (1) Chemotherapy ±Avastin 修訂為 Consider endocrine therapy, if not endocrine refracty C/T (2) ER and PR (-); ER/PR (+) and endocrine refracty and HER2 (+) 分為兩部分, 分別為 BINV-15 Pertuzumab + Trastuzumab + taxance (preferred) Ado-trastuzumab eutansine(tdm1) Trastuzumab + C/T 15.Invasive Breast Cancer: (1) Postmenopausal Aromatase inhibit f 5 y 新增 consider tamoxifen f 5y to complete 10y (2) Premenopausal No further endocrine therapy another Tamoxifen 5y 修訂為 No further endocrine therapy Tamoxifen f 5y to complete 10y (3) Aromastse inhibit f 5 y Tamoxifen f 2-3y Aromastse inhibit f 2-3 y 新增 Aromatase inhibit f additional 5y (4) Tamoxifen f y Aromastse inhibit f 5y 修訂為 Aromastse inhibit f 5y Tamoxifen f 5y to complete 10y BINV-11 BINV-12 BINV-13 BINV-15 BINV-16 BINV-19

125 乳癌修訂紀錄 修訂日期 修訂內容摘要 修訂頁次 版本 (5) Tamoxifen f 5y 10y 修訂為 Tamoxifen f 5y Up to 10y 16. 新增 Breast cancer IORT Guidelines from Kaohsiung Medical University Chung-Ho Memial Hospital IORT-1

126 Lobular Carcinoma In Situ DIAGNOSIS WORKUP RISK REDUCTION SURVEILLANCE Biopsy was ce needle biopsy (less than surgical Perfm surgical excision LCIS without other cancer Counseling regarding risk reduction,see NCCN Guidelines f Breast Cancer Risk Reduction Surveillance as per *NCCN Guidelines f Breast Cancer Risk Reduction * NCCN Guidelines f Breast Cancer Screening and Diagnosis LCIS Stage0, Tis,N0,M0 *Histy and physical *Diagnosis bilateral mammogram biopsy) Ductal carcinoma in situ (DCIS) See NCCN Guidelines f DCIS (DCIS -1) *Pathology review Initial biopsy was surgical biopsy Invasive breast See NCCN Guidelines f cancer Invasive breast (BINV-1) LCIS-1

127 Ductal Carcinoma In Situ (DCIS) Diagnosis Wkup Primary Treatment DCIS Postsurgical Treatment Surveillance Follow-up DCIS Stage 0 Tis, N0, M0 *Histy and physical exam *Diagnostic bilateral mammogram, sonography, *Pathology review *Determination Of Tum Estrogen recept (ER) status Lumpectomy without lymph node dissection + RT Total mastectomy without lymph node dissection ± reconstruction Postsurgical Treatment Adjuvant treatment: Consider tamoxifen f 5 years f: -Patients treated with breast-conserving therapy (lumpectomy) and RT, especially f those with ER (+) DCIS -The benefit of tamoxifen f ER (-) DCIS is uncertain -Patients treated with excision alone Risk reduction therapy f contralateral breast: -Counseling regarding consideration of tamoxifen f risk reduction *Interval histy and physical exam every 6 mo f 5 y, then annually *Mammogram every 12 mo DCIS-1

128 Invasive Breast Cancer CLINICAL STAGE WORKUP Stage I T1, N0, M0 Stage IIA T0, N1, M0 T1, N1, M0 T2, N0,M0 Stage IIB T2, N1, M0 T3, N0, M0 Or Stage IIIA T3, N1, M0 *Histy and physical exam *Diagnostic bilateral mammogram,+/- ultrasound *Pathology review *Determination of tum estrogen/progesterone recept (ER/PR) status and HER-2 status *Breast MRI (optional) *CBC *Liver function tests and alkaline phosphatase *Bone scan (optional) (Indicated if localized symptoms elevated alkaline phosphatase if T3, N1, M0) *Abdominal CT US MRI (optional) (indicated if elevated alkaline phosphatase, abnmal LFTs, abnmal symptoms, abnmal physical exam of the abdomen) *Chest CT (optional)(if pulmonary symptoms present) See Locegional Treatment (BINV-2) *Bone scan 本院無設備, 需轉介至高醫檢查 BINV-1

129 Invasive Breast Cancer LOCOREGIONAL TREATMENT OF CLINICAL STAGE I, IIA, OR IIB DISEASE OR T3, N1, M0 4 positive RT to whole breast with without boost to tum bed, infraclavicular region and axillary nodes supraclavicular area, Strongly consider RT to internal mammary nodes, RT should follow C/T when C/T is indicated Lumpectomy with surgical axillary staging 1-3 positive axillary nodes RT to whole breast with without boost to tum bed, strongly consider RT to infraclavicular region and supraclavicular area, internal mammary nodes, RT should follow C/T when C/Tis indicated See BINV-4~7 Negative axillary nodes RT to whole breast with without boost to tum bed consideration of accelerated partial breast irradiation (APBI) in selected patients. RT should follow C/T when C/T is indicated Total mastectomy with surgical axillary staging ± reconstruction See Locegional Treatment (BINV-3) If T2 T3 and fulfills criteria f breast conserving therapy except f size Consider Preoperative Chemotherapy Guideline(BINV-10) BINV-2

130 Invasive Breast Cancer LOCOREGIONAL TREATMENT OF CLINICAL STAGE I, IIA, OR IIB DISEASE OR T3, N1, M0 4 positive axillary nodese Post C/T RT to chest wall + infraclavicular and supraclavicular area, internal mammary nodes Total mastectomy 1-3 positive axillary nodes Post C/T strongly consider RT to chest wall + infraclavicular and supraclavicular area, internal mammary nodes with surgical axillarystaging ± reconstruction Negative axillary nodes and tum > 5 cm Post C/T RT to chest wall ± infraclavicular and supraclavicular area ± internal mammary nodes See BINV-4~7 Margins positive Re-excision to negative margin is preferred. If not feasible, then post C/T strongly consider RT to chest wall ± infraclavicular ± supraclavicular area ± internal Negative axillary nodes mammary nodes and tum 5 cm and negative margins but<1mm Consider RT to chest wall Negative axillary nodes and tum 5 cm and margins 1mm No RT BINV-3

131 Invasive Breast Cancer SYSTEMIC ADJUVANT TREATMENT - HORMONE RECEPTOR (+)-HER2 (+)DISEASE Tum 0.5 cm Microinvasive pn0 pn1mi Consider adjuvant endocrine therapy Adjuvant endocrine therapy Adjuvant C/T with trastuzumab followed by endocrine therapy pt1, pt2, pt3; and pn0 pn1mi ( 2 mm axillary node metastasis) Tum cm Adjuvant endocrine therapy ± adjuvant C/T with trastuzumab ER(+) Histology: and/ Ductal, NOS PR(+) and Her2(+) Lobular Mixed Metaplastic Tum >1 cm Adjuvant endocrine therapy + Adjuvant C/T with trastuzumab Node (+) (one me metastasis >2 mm to one me ipsilateral axillary lymph nodes) Adjuvant ebdocrine therapy + adjuvantc/t± pertuzumab with trastuzumab BINV-4

132 Invasive Breast Cancer SYSTEMIC ADJUVANT TREATMENT - HORMONE RECEPTOR (+)-HER2 (-)DISEASE pn0 Consider adjuvant endocrine therapy pt1, pt2, pt3;and pn0 pn1mi( 2 mm axillary node Tum 0.5 cm Microinvasive pn1mi Adjuvant endocrine therapy ± adjuvant C/T ER(+) and/ PR(+) Histology: Ductal, NOS Lobular metastasis Tum >0.5 cm Adjuvant endocrine therapy ± adjuvant C/T and Mixed Her2 (-) Metaplastic Node (+) (one me metastasis >2 mm to one me ipsilateral axillary lymph nodes) Adjuvant endocrine therapy + adjuvant C/T BINV-5

133 Invasive Breast Cancer SYSTEMIC ADJUVANT TREATMENT - HORMONE RECEPTOR (-)-HER2 (+)DISEASE pn0 pt1, pt2, pt3; Tum 0.5 cm Microinvasive pn1mi Consider adjuvantc/twith and pn0 pn1mi ( 2 mm axillary Tum cm, trastuzumab node metastasis) ER(-) and PR(-) and Her2(+) Histology: Ductal, NOS Lobular Mixed Metaplastic Node (+) (one me Tum >1 cm metastasis>2 mm to one Adjuvant C/T with trastuzumab+ me ipsilateral axillary pertuzumab lymph nodes) BINV-6

134 Invasive Breast Cancer SYSTEMIC ADJUVANT TREATMENT - HORMONE RECEPTOR (-)-HER2 (-)DISEASE pn0 No adjuvant therapy Tum 0.5 cm pt1, pt2, pt3; Microinvasive pn1mi Consider adjuvant C/T and pn0 pn1mi ( 2 mm axillary Tum cm, ER(-) Histology: node metastasis) and PR(-) Ductal, NOS Lobular Tum >1 cm Consideradjuvant C/T and Her2(-) Mixed Metaplastic Node (+) (one me metastasis >2 mm to one me ipsilateral AdjuvantC/T axillary lymph nodes) Mixed lobular and ductal carcinoma as well as metaplastic carcinoma should be graded based on the ductal component and treated based on this grading. The metaplastic mixed component does not alter prognosis. There are insufficient data to make chemotherapy recommendations f those over 70 y old. Treatment should be individualized with consideration of combid conditions. BINV-7

135 Invasive Breast Cancer Preoperative Chemotherapy Guideline Clinical Stage Wkup Stage IIA T2, N0,M0 Stage IIB T2, N1, M0 T3, N0, M0 Stage IIIA T3, N1, M0 and Fulfills criteria f breast conserving surgery except f tum size *Histy and physical exam *Diagnostic bilateral mammogram, ultrasound as necessary *Pathology review *Determination of tum (ER/PR) status and HER-2 status *Breast MRI (optional) *CBC *Liver function tests and/ alkaline phosphatase *Bone scan (optional) (indicated if localized symptoms elevated alkaline phosphatase if T3, N1, M0) *Abdominal CT US MRI (optional) (indicated if elevated alkaline phosphatase, abnmal LFTs, abdominal symptoms, abnmal physical examination of the abdomen) *Chest CT(optional) See BINV-9 *Bone scan 本院無設備, 需轉介至高醫檢查 BINV-8

136 Invasive Breast Cancer Preoperative Chemotherapy Guideline Primary Treatment Desires breast preservation Ce biopsy of breast tum, consider FNA of clinically(+) axillary lymphnode(s) sentinel lymph nodeprocedure ifclinically (-) axillary lymphnode(s) Localizationo f tum bedf futuresurgical management Preoperative C/T (endocrinetherapy alone may be considered f recept(+) disease in postmenopausal patients) No response after 3-4 cycles Progressive disease Partial response, lumpectomy Partial Consider AlternativeC/T No response after 3-4 cycles Progressive disease Partial response, lumpectomy not possible See Mastectomy Pathway (BINV-10) response, lumpectomy possible See Lumpectomy Pathway(BINV-10) Complete response Does not desire breast See Stage I and II breast cancer preservation (BINV-3) See Surgical Axillary Staging A number od combination and single agent chemotherapy regimens have activity in preoperative setting.in general those chemotherapy recommended in the adjuvant settingconsidered in preoperative setting.if treated with hmonal therapy.an aromatase inhibit is preferered f postmenopausal women. BINV-9

137 Invasive Breast Cancer Preoperative Chemotherapy Guideline Local Treatment Adjuvant Treatment Mastectomy and surgical axillary staging ± reconstruction. If sentinel lymph node biopsy perfmed prec/t and negative findings, may omit axillary lymph node dissection Lumpectomy with surgical axillary staging. If sentinel lymph node biopsy perfmed PreC/T and negative findings, may omit axillary lymph node dissection Consider additional C/T 1. Adjuvant RT post-mastectomy is based on prec/t tum characteristics and endocrine therapy if ER(+) and / PR(+) 2. If HER2 (+) complete up to one year of HER2 targeted therapy with trastuzumab± pretuzumab, maybe administered concurrently with RT and with endocrine therapy if indicated. See Surveillance/ Follow-up (BINV-13) 1.Chemotherapy and hmonal therapy used as adjuvant therapy should be given sequentially with hmonal therapy following chemotherapy. The benefits of chemotherapy and of hmonal therapy are additive. However, the absolute benefit from chemotherapy may be small. The decision to add chemotherapy to hmonal therapy should be individualized, especially in those with a favable prognosis and in women age 60y where the incremental benefit of chemotherapy may be smaller. Available data suggest sequential concurrent hmonal therapy with RT is acceptable. 2.Axillary staging may include sentinel node biopsy level l/ll dissection. 3.Whole breast irradiation with boost (by photons, brachytherapy electron beam) to tum bed. Boost to tum bed is especially encouraged in those 50 y of age younger. If internal mammary lymph nodes are clinically pathologically positive, RT should be given to the internal mammary nodes, otherwise the treatment to the internal mammary nodes is at the discretion of the treating radiation oncologist. CT treatment planning should be utilized in all cases where RT is delivered to the internal mammary lymph node field. BINV-10

138 Invasive Breast Cancer Locally Advanced Invasive Breast Cancer Clinical Stage Wkup Stage IIIA T0, N2, M0 T1, N2, M0 T2, N2,M0 T3, N2,M0 Stage IIIB T4, N0, M0 T4, N1, M0 T4, N2,M0 Stage IIIC Any T, N3, M0 *Histy and physical exam *Diagnostic bilateral mammogram, ultrasound as necessary *Pathology review *Prechemotherapy determination of tum ER/PRrecept statusand HER-2 statusb *Breast MRI (optional) *CBC *Liver function tests *Chest CT(optional) *Abdominal CT US MRI *Bone scan See Preoperative Chemotherapy and Locegional Treatment (BINV-12) Stage IV Any T, any N, M1 See Initial Wkup f Stage IV Disease (BINV-13) BINV-11

139 Invasive Breast Cancer Preoperative Chemotherapyf Locally Advanced Invasive Breast Cancer Locegional Treatment Adjuvant Treatment Response Total mastectomy + level I/II axillary dissection + RT ± reconstruction lumpectomy + surgical axillary staging + RT Additional C/T + endocrine therapy if ER(+) and/ PR(+) complete up to one year of trastuzumab ± pertuzumab Preoperative C/T preferred therapy if HER2(+) See Response - See above Surveillance/ pathway Follow-up No responseres Consider additional systemic C/T and/ preoperative RT No response Individualized treatment (BINV-13) BINV-12

140 Invasive Breast Cancer Surveillance/Follow-up Recurrence / Stage IV Disease Wkup *Interval histy and physical exam every 4-6 mo f 5 y, then every 12 mo *Mammogram every 12 mo *Women on tamoxifen :annual gynecologic assessment every 12 mo if uterus present *Women on an aromatase inhibit whoexperience ovarian failure secondary totreatment should have moniting of bone health *Assess and encourage adherence to adjuvant endocrine therapy *Histy and Physical exam *CBC *Liver function tests *Chest imaging *Bone scan *X-rays of symptomatic bones and longand weight-bearing bones abnmal onbone scan *Consider abdominal CT MRI *Biopsy documentation of first recurrence, if possible *Consider determination of tum ER/PRand HER-2 status if unknown, iginally (-) not over-expressed *PET scan (optional) Local disease only Systemic disease Treatment of Recurrence/ Stage IV Disease (BINV-14) BINV-13

141 Invasive Breast Cancer SystemicTreatment of Recurrent Stage IV Disease Initial treatment with lumpectomy + RT Total mastectomy + axillary lymph node staging if level I/II axillary dissection not previously done Localonly recurrence Initial treatment with mastectomy + level I/II axillary dissection and pri RT Surgical resection if possible Initial treatment with mastectomy Surgical resection if possible + RT no pri RT Consider Axillary recurrence Surgical resection if possible + RT if possible systemic therapy Regional only local and regional recurrence Supraclavicular recurrence Internal mammary node recurrence RT if possible Systemic disease Bone disease present Add denosumab (prolia), zoledronic acid, pamidronate (Aredia) ER and/ PR (+) ; HER2 (-) ER and/ PR(+) ; HER2 (+) ER and PR (-), ER and/ PR (+) and endocrine refracty ; HER2 (-) See BINV-15 See BIVN-16 Bone disease not present ER and/ PR (-) ER and/ PR (+) and endocrine refracty ; HER2 (+) BINV-14

142 Invasive Breast Cancer SystemicTreatment of Recurrent Stage IV Disease ER and/ PR(+); HER2 (-)(+) Pri endocrine therapy within 1y Visceral crisis Consider initialc/t ER and/ PR(+); HER2 (-) ER and/ PR (+); HER2 (+) No pri endocrine therapy within 1y Non visceral crisis Visceral crisis C/T Hmone ± CDK4/6 inhibit Consider initial C/T See BINV-17 Non visceral crisis Hmone ± Herceptin C/T + Herceptin BINV-15

143 Invasive Breast Cancer SystemicTreatment of Recurrent Stage IV Disease ER and PR (-), ER and/ PR (+)andendocrine refracty; HER2 (-) ER/PR(-), ER/PR (+) and endocrine refracty and HER2 (-) Consider endocrine therapy, if not endocrine refracty C/T No response to 3sequential regimens ECOG perfmancestatus 3 Consider no furthercytotoxic therapy; transition to palliative care ER and PR (-), ER and/ PR(+) and endocrine refracty; HER2 (+) ER and PR (-); BINV-15 ER/PR (+) and endocrine rfracty and HER2 (+) Pertuzumab + Trastuzumab + taxance (preferred) Ado-trastuzumab eutansine HER 2 targeted therapy No response to 3 sequential regimens ECOG perfmance status 3 Consider no further cytotoxic therapy ; transition to palliative care (TDM1) Trastuzumab + C/T BINV-16

144 Invasive Breast Cancer Follow-up Therapyf Hmone Treatmentof Recurrence/Stage IV Disease Continue endocrine No clinical benefit after Yes C/T therapy until progression unacceptable toxicity Progression 3consecutive hmonal therapy regimens Symptomatic visceral disease No Trial of new Endocrine therapy BINV-17

145 Invasive Breast Cancer Surgical Auxiliary Stage- Stage I,IIA,IIB,IIIA; T3,N1,M0 FNA ce biopsy (+) Axillary dissection level I/II Clinically node (+) at time of diagnosis FNA ce biopsy (-) Clinical stage I,IIA,IIB Sentinel node (-) No further surgery and IIIA T3,N1,M0 Clinically node(-) at time of diagnosis Sentinel node mapping and excision Sentinel node (+) Meets ALL of the following criteria: *T1 T2 tum *1 2 positive SLNs *Breast conserving therapy *Whole breast RT planned Yes to all Axillary dissection level I/II consider no further surgery *No nooadjuvant C/T No Sentinel node not identified Axillary dissection level I/II BINV-18

146 Invasive Breast Cancer AdjuvantEndocrine Therapy Premenopausal at diagnosis Tamoxifen f 5 y ± ovarian suppression ablation Postmenopausal Premenopausal Aromatase inhibit f 5 y consider tamoxifen f 5y to complete 10y No further endocrine therapy Tamoxifen f 5y to complete 10y Aromastse inhibit f 5 y Aromatase inhibit f additional 5y Tamoxifen f 2-3y Aromastse inhibit to complete 5y of endocrine therapy up to 5y of an aromastase inhibit Aromastse inhibit f 2-3 y Tamoxifen to complete 5y of endocrine therapy Postmenopausal at diagnosis Tamoxifen f y Aromastse inhibit f 5y Tamoxifen f 5y to complete 10y Women with a contraindication to aromatase inhibits,who decline aromatase inhibits, who are intolerant of the aromastase inhibits Tamoxifen f 5y up to 10y BINV-19

147 Breast cancer IORT Guidelines I. Tum Type: DCIS, Invasive ductal carcinoma, Lobular carcinoma, Mucinous carcinoma, Medullary carcinoma Primary recurrent (single previouswhole breast irradiation)tum II. Tum size: Clinical tum size < 3cm III. Sentinel LNs (f primary tum IORT): Negative: IORT 20 Gy to tum bed Positive: IORT 20 Gy to tum bed + EBRT 40 Gy/15 fx EBRT 50 Gy/25 fx to whole breast, axillary and supraclavicle lymphatic drainage area of the involved side FpT1-2N0-1(LNs1-2),luminaltype,andfthosewhefuse whole breast irradiation ->might consider IORT to tumour bed andaxillary LNs f 20Gy,each. IV. Exclusion criteria: DCIS with extensive intraductal component (EIC) IDC with multiple foci >= 3foci Caution should be taken when 2 foci areseparated f longdistance IORT-1

148 參考文獻 1.Breast Cancer NCCN V from 2. Robert NJ,Dieras V,Glaspy J,et al.ribbon-1:randomized,double-blind,placebo-controlled,phase III trial of chemotherapy with without bevacizumab f firsy-line treatment of human epidermal growth fact recept 2-negative,locally recurrent metastatic breast cancer.j Clin Oncol 2011;29: Blackwell KL,Burstein HJ,Stniolo AM,et al.overall survival benefit with lapatinib in combination with trastuzumab f patients with human epidermal growth fact recept 2-positive metastatic breast cancer:final result from the EGF Study. J Clin Oncol 2012;30: Badwe R, Parmar V, Hawaldar R, et al. Surgical removal of primary breast tum and axillary lymph nodes in women with metastatic breast cancer at first presentation: a randomized controlled trial. Presented at:2013[abtract]. San Antonio Breast Cancer Symposium 2013:Abstract S Smerage JB, Barlow WE, Htobagyi GN, et al. Circulating tum cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol 2014;32: Breast Guideline( 高醫 IORT)

149 Cancer of the Cervical Treatment Guideline KMHK 初訂日期 : 97 年 1 月 1 日 修訂日期 : 107 年 6 月 5 日

150 子宮頸癌修訂紀錄 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 E3~ 年 104 年 105 年 1. 子宮頸癌診療指引新制訂 1. 新增子宮頸篩檢凖則多專科會議討論檢視後未修改多專科會議討論檢視後未修改多專科會議討論檢視後未修改 1.stage Ia1 做 simple Hysterectomy 或 Conization;stage Ia2 以上評估是否可開刀做 radical hysterectomy 且要評估 lymph node 情形, 決定是否要做化療及放射線治療 多專科會議討論檢視後未修改多專科會議討論檢視後未修改 1.IB1 2A1 之前沒辦法手術病人就 R/T, 最新指引是考慮 risk fact 較高病人會將 concurrent chemadiotherapy 加進去 年 根據 NCCN 最新版次, 團隊成員進行導讀及共識討, 決議今年暫不修訂, 維持去年版本 106 年 1. 新增子宮頸癌治療前檢查 2. 新增子宮頸癌 IA1 Surveillance 之時程 E-1 E 年 1.Stage IA IB 內容字眼上做少許變動修改 E-2 6.0

151 Cervical Cancer 子宮頸癌治療前檢查 必要檢查 : 1. 病史及理學檢查 2. ( 血液常規 ) 全血球計數 ; 常規生化檢驗 3. 子宮頸切片之組織病理檢查 4. 詳細的內診檢查 5. 胸部 X 光 選擇性檢查 : 1. 血清腫瘤標記檢驗 ( 如 CA-125 CEA SCC) 2. 膀胱或直腸鏡檢 3. 腹部或婦產科超音波檢查 4. 骨轉移攝影 5. 正子攝影 6. 子宮頸錐狀手術 ( 當子宮頸切片之組織病理檢查結果為微侵襲癌者 ) 7. 腎盂攝影 (IVP) 或腹部及骨盆電腦斷層或核磁共振檢查 E-1

152 Cancer of the Cervical Treatment Guideline STAGING TREATMENT Completed Simple Hysterectomy Stage IA Stage IA1 (Microinvasive), LVSI(-) Childbearing Not completed Conization +Surveillance (q3-6months/2 years q6-12months/3-5years q12months/>5 years) -Stage IA2, -Stage IA,LVSI(+) Operable Ye No RH + PLND Pelvic EBRT+Brachytherapy Stage IB Tum size Histology (Biopsy) paraatic nodes (MRI CT PET) Stage IB1 < 4 cm and StageIIA1 Squamous cell ca Adeno ca. Small cell ca. Stage IB2 > 4 cm and StageIIA2 enlarged paraatic LN pelvic LN Operable Operable Preop CCRT Cisplatin + 5 FU No Ye No Ye Good response Po response Pelvic+EBRT +Brachytherapy RH + PLND CCRT(Cisplatincontaining RH + PLND Histology(surgical specimen) Tum size > 4cm LVI (+) Deep stromal invasion Lymph node (+) Positive margin Parametrial invasion RH + PLND No Ye Completed RT + chemotherapy Obs Pelvic paraatic RT+chemo -therapy E-2 說明 : 因本院無放射治療設備, 故治療需放射線治療及同步化學治療病患協助轉診至高醫或其他院治療

153 Cancer of the Cervical Treatment Guideline STAGING Stage II A1, II A2 Operability Yes No TREATMENT RH + PLND Concurrent chemotherapy and radiation Histology(surgical specimen) Tum size >4cm LVI(+) Deep stromal invasion Lymph node(+) Positive margin Parametrial invasion No Yes Surveillance Pelvic Paraatic RT + chemotherapy Stage IIB, III, IVA Concurrent chemotherapy and radiation (pelvic paraatic) Stage IVB Palliation (chemotherapy / and radiation) Yes Chemotherapy, palliation Recurrent Ca.. with Distant intra-abdominal paraatic metastases No Pri treatment Pelvic RT Ye Central Side wall Pelvic exenteration RT Chemotherapy No Completed RT ± Chemotherapy E-3 說明 : 因本院無放射治療設備, 故治療需放射線治療及同步化學治療病患協助轉診至高醫或其他院治療

154 Cancer of the Cervical Treatment Guideline FINDINGS ON INITIAL SCREENING/ PAPTEST COLPOSCOPY FINDINGS CERVICAL BIOPSY FINDINGS Nmal Repeat Pap test at 6 mo FOLLOW-UP TREATMENT If LSIL persists f 24 mo,consider treatment CIN I Repeat Pap test every 6 mo If returns to nmal, Pap test every 12 mo If Pap test indicates HSIL Colposcopy CIN II CKC LEEP Cryotherapy Laser Satisfacty colposcopy Cervical biopsy CIN III CKC LEEP Cryotherapy Laser Total hysterectomy Microinvasive NCCN Cervical Cancer Treatment Guidelines Invasive NCCN Cervical Cancer Treatment Guidelines LSIL/ASCUS Negative Cervical intraepithelial neoplasia (CIN) I ECC FINDINGS Positive Negative Positive Negative CIN I CIN II III CIN I CIN II III Repeat Pap test at 6mo Repeat Pap test at 6mo Repeat Pap test at 6mo Repeat Pap test at 6mo CKC LEEP CKC LEEP Unsatisfacty colposcopy Cervical biopsy +ECC CIN II Positive CIN II III CKC LEEP Negative CKC LEEP Cryotherapy Laser CKC=Cold-knife conization ECC=Endocervical curretage LEEP=Loop electrosurgical excision procedure CIN III Cancer Positive Negative CIN II III CKC LEEP Total hysterectomy after CKC LEEP f definitive diagnosis CKC LEEP Cryotherapy Laser Total hysterectomy KMU Cervical Cancer Treatment Guidelines E-4

155 Cervical Screening 子宮頸篩檢準則 FINDINGS ON INITIAL SCREENING/ PAPTEST COLPOSCOPY FINDINGS CERVICAL BIOPSY FINDINGS Nmal Review screening Pap test FOLLOW-UP If high grade, consider LEEP f definitive TREATMENT If LSIL persists f 24 mo,consider treatment CIN I Repeat Pap test every 6 mo If returns to nmal,pap test every 12 mo If Pap test indicates HSIL Colposcopy CIN II CKC LEEP Cryotherapy Laser Satisfacty colposcopy Cervical biopsy CIN III CKC LEEP Cryotherapy Laser Consider Total hysterectomy Microinvasive NCCN Cervical Cancer Treatment Guidelines Invasive ECC FINDINGS NCCN Cervical Cancer Treatment Guidelines HSIL Negative Positive f dysplasia Negative Repeat Pap test at 6mo CKC LEEP CIN I Positive f dysplasia CIN I, II, III) CKC LEEP Negative Repeat Pap test at 6mo Unsatisfacty colposcopy CKC=Cold-knife conization ECC=Endocervical curretage LEEP=Loop electrosurgical excision procedure Cervical biopsy +ECC CIN II CIN III Cancer Positive f dysplasia CIN I, II, III) Negative Positive f dysplasia CIN I, II, III) Negative CKC LEEP CKC LEEP Cryotherapy Laser CKC LEEP Total hysterectomy after CKC LEEP f definitive diagnosis CKC LEEP Cryotherapy Laser Total hysterectomy KMU Cervical Cancer Treatment Guidelines E-5

156 Cervical Screening 子宮頸篩檢準則 FINDINGS ATTREATMENT FOLLOW-UP POST-TREATMENT After CKC LEEP f CIN Negative margins margin status unknown Cryotherapy Laser Nmal (no dysplasia) CIN I CIN II CIN III Margin CIN I Pap test at 6 mo mo Pap test at 6 mo Pap test at 6 mo Pap test at 6 mo Pap test at 6 mo Consider ECC (categy 2B) Nmal Negative ASCUS LSIL HSIL Resume annual PAP testing Repeat Pap test at 6 mo Repeat Pap test at 6 mo Repeat Pap test at 6 mo Consider colposcopy Colposcopy Negative ASCUS LSIL HSIL Resume annual PAP testing Repeat Pap test at 6 mo Repeat Pap test at 6 mo Consider colposcopy Colposcopy Positive margins Margin CIN II,III Pap test at 6 mo Consider ECC (categy 2B) Negative ASCUS HSIL LSIL Repeat Pap test at 6mo Repeat Pap test at 6mo Colposcopy Total hysterectomy Negative Resume annual PAP testing E-6

157 Cervical Screening 子宮頸篩檢準則 FOLLOW-UP OF CERVICAL BIOPSY/ENDOMETRIAL BIOPSY FINDINGS FOLLOW-UP Negative No further evaluation of endometrium Endometrial biopsy Hyperplasia Atypical hyperplasia Consider dilatation and Curettage(D&C) D&C CIN I,II III See E7 f Follow-up of CKC AGCUS AGCUS with endometrial cells Fav endometrial cells Age > 40yr Endometrial cancer risk facts f Colposcopy ECC and endometrial biopsy ECC Cancer Nondiagnostic Nmal CIN I, II, III KMU Endometrial Cancer Treatment Guidelines Consider repeat depending on ECC/ cervical biopsy findings consider transvaginal ultrasound f metrial endo stripe thickness Individualized follow-up based on review of AGCUS smear CKC If CKC Adenocarcinoma in situ/ glandular intraepitheli al neoplasia Consider referral to gynecologic oncologist Negative margins Negative margins, fertility desired Hysterectomy (standard preferred) Pap test with ECC at 6 mo Requires consent / counseling Recommend hysterectomy when childbearing completed AGCUS fav cervical neoplasia Colposcopy ECC f Endometrial Cancer Risk Facts:Obesity,estrogen replacement therapy,polycystic ovarian disease, tamoxifen,anovulation Cervical biopsy Adenocarcinoma in situ Cancer Nmal Adenocarcinoma in situ CIN I CKC KMU Endometrial/Cervical Cancer Treatment Guidelines Individualized follow-up based on review of AGCUS smear CKC Repeat Pap test at 6 mo if ECC negative Cancer Positive margins KMU Cervical Cancer Treatment Guidelines Total hysterectomy Repeat CKC at 3 mo If fertility desired, consent / counseling required Recommend hysterectomy when childbearing completed CIN II, III (squamous) CKC E-7

158 分期 Cervix Uteri Definition of Primary Tum (T) T Categy FIGO Stage T Criteria TX Primary tum cannot be assessed T0 No evidence of primary tum T1 I Cervical carcinoma confined to the uterus (extension to cpus should be disregarded) T1a IA Invasive carcinoma diagnosed only by microscopy. Stromal invasion with a maximum depth of 5.0 mm measured from the base of the epithelium and a hizontal spread of 7.0 mm less. Vascular space involvement, venous lymphatic, dose not affect classification. T1a1 IA1 Measured stromal invasion of 3.0 mm less in depth and 7.0 mm less in hizontal spread T1a2 IA2 Measured stromal invasion of me than 3.0 mm and not me than 5.0 mm, with a hizontal spread of 7.0 mm less T1b IB Clinically visible lesion confined to the cervix microscopic lesion greater than T1a/IA2. Includes all macroscopically visible lesions, even those with superficial invasion. T1b1 IB1 Clinically visible lesion 4.0 cm less in greatest dimension T1b2 IB2 Clinically visible lesion me than 4.0 cm in greatest dimension T2 II Cervical carcinoma invading beyond the uterus but not to the pelvic wall to lower third of the vagina T2a IIA Tum without parametrial invasion T2a1 IIA1 Clinically visible lesion 4.0 cm less in greatest dimension T2a2 IIA2 Clinically visible lesion me than 4.0 cm in greatest dimension T2b IIB Tum with parametrial invasion T3 III Tum extending to the pelvic sidewall* and/ involving the lower third of the vagina and/ causing hydronephrosis nonfunctioning kidney T3a IIIA Tum involving the lower third of the vagina but not extending to the pelvic wall T3b IIIB Tum extending to the pelvic wall and/ causing hydronephrosis nonfunctioning kidney T4 IV Tum invading the mucosa of the bladder rectum and/ extending beyond the true pelvis (bullous edema is not E-8

159 sufficient evidence to classify a tum as T4) *The Pelvic sidewall is defined as the muscle, fascia, neurovascular structures, and skeletal ptions of the bony pelvis. On rectal examination, there is no cancer-free space between the tum and pelvic sidewall. Definition of Regional Lymph Node (N) N Categy FIGO Stage N Criteria NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N0(i+) Isolated tum cells in regional lymph node(s) no greater than 0.2 mm N1 Regional lymph node metastasis Definition of Distant Metastasis(M) M Categy FIGO Stage M Criteria M0 No distant metastasis M1 IVB Distant metastasis (including peritoneal spread involvement of the supraclavicular, mediastinal, distant lymph node; lung; liver; bone ) E-9

160 參考文獻 1.J Clin Oncol.2002 Apr 1;20(7): Randomized trial of cisplatin and ifosfamide with without bleomycin in squamous carcinoma of the cervix: a gynecologic oncology group study 2. Am J Obstet Gynecol 2007;197:503.e1-503.e6 3. Comparison of carboplatin- and cisplatin-based concurrent chemadiotherapy in locally advanced cervical cancer patients with mbidity risks.nam EJ, Lee M, Yim GW, Kim JH, Kim S, Kim SW, Kim JW, Kim YT Oncologist. 2013;18(7): Moe DH, Blessing JA, McQuellon RP, et al. Phase III study of cisplatin with without paclitaxel in stage IVB, recurrent, persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol 2004;22: Kitagawa R, Katsumata N, Shibata T, et al. A randomized,phaseiii trial of paclitaxel plus carboplatin (TC) versus paclitaxel plus cisplatin(tp) in stage IVb, persistent recurrent cervical cancer: Japan Clinical Oncology Group study (JCOG0505) [abstract]. J Clin Oncol 2012;30(Suppl 15):Abstract 5006.

161 Cancer of the Endometrial Treatment Guideline KMHK 初訂日期 : 97 年 1 月 1 日 修訂日期 :107 年 6 月 5 日

162 子宮內膜癌修訂紀錄修訂日期修訂內容摘要修訂頁次版本 104 年 105 年 子宮內膜癌診療指引新制訂 1.Endomctrial 改為 Endomctrial fractional biopsy 2.f 改為 f cancer cell 3.Hysteroscopel 改為 Hysteroscopic biopsy 4.Surgical staging 刪除 5.Medically 改為 Medically inoperable 6.Medically 改為 Medically operable 7.Cytology 改為 Peritoneal washings f cytology Stage 改為 Stage IA 8.Cytology 刪除 9.adwquately debulking 改為 adequately debulking 10.Inadwquately debulking 改為 inadequately debulking E7~10 E7 E7 E7 E7 E7 E7 E7 E7 E10 E10 E 年 多專科會議討論檢視後未修改 107 年 Potential adverse risk fact 增加.Lower uterine surface E involvement.cervical involvement.glandular involvement 1.Pelvic RT+Vaginal brachytherapy 改為 Vaginal brachytherapy and/ pelvic RT E12 2.Chemotherapy and/ tum-directed RT 改為 C/T and/ EBRT ± brady 3.Pelvic 改為 Pelvic node positive

163 Endometrial Cancer 子宮內膜癌治療前檢查 必要檢查 : 1. 病史及理學檢查 2.( 血液常規 ) 全血球計數 ; 常規生化檢驗 3. 子宮頸內頸 / 子宮內膜刮除術之組織病理檢查 4. 胸部 X 光 5. 腹部及骨盆核磁共振檢查或電腦斷層 選擇性檢查 : 1. 腹部超音波檢查 2. 膀胱或直腸鏡檢 3. 血清腫瘤標記檢驗 ( 如 CA-125) 4. 正子攝影 5. 疑子宮頸侵犯 : 子宮頸切片檢查 E-10

164 Cancer of the Endometrial Treatment (+) f cancer cell Medically inoperable Medically operable Primary radiation Primary surgery Endomctrial fractional biopsy (+) f cancer (-) f cancer cell Hysteroscopic biopsy (-) f cancer Follow-up G1 G2 G3 Adverse risk(-) observe Observe Vaginal Observe Vaginal Completely surgical staging:.ath+bso.peritoneal washings f cytology.pelvic lymphadenectomy.para-atic lymphadenectomy(optional) Stage IA Adverse risk(+) Observe Vaginal brachytherapy Observe brachytherapy Observe Vaginal Brachytherapy and/ pelvic RT Observe brachytherapy Observe Vaginal Brachytherapy and/ pelvic RT Observe Potential adverse risk fact:.age.positive lymphovascular invasion.tum size.lower uterine surface involvement.cervical involvement.glandular involvement Stage IB Adverse risk(-) Adverse risk(+) Vaginal brachytherapy Observe Vaginal Brachytherapy and/ pelvic RT Vaginal brachytherapy Observe Vaginal Brachytherapy and/ pelvic RT Vaginal Brachytherapy and/ pelvic RT Observe pelvic RT and/ vaginal brachytherapy +chemotherapy E-11

165 Cancer of the Endometrial Treatment Guideline Completely surgical staging:.ath+bso.cytology.pelvic lymphadenectomy.para-atic lymphadenectomy (optional) Stage II Stage IIIA Stage IIIB G1 G2 G3 Vaginal brachytherapy and/ pelvic RT Vaginal brachytherapy and/ pelvic RT Pelvic RT±Vaginal brachytherapy±chemotherapy Chemotherapy+RT Or tum-directed RT+ Chemotherapy Or Pelvic RT+Vaginal brachytherapy Chemotherapy+RT Or tum-directed RT+ Chemotherapy Or Pelvic RT+Vaginal brachytherapy Chemotherapy+RT Or tum-directed RT+ Chemotherapy Or Pelvic RT+Vaginal brachytherapy C/T and/ EBRT ± brady Chemotherapy and/ tum-directed RT + brady Stage IIIC1 Pelvic node positive Chemotherapy and/ tum-directed RT ± brady Stage IIIC2 Para-atic node positive ± Pelvic node positive Chemotherapy and/ tum-directed RT ± brady Stage IVA and B Debulking and with no gross residual disease microscopic abdominal disease Chemotherapy ± RT ± brady Stage I with positive cytology Large tum High grade Deep myometrium Invasion Adjuvant chemotherapy E-12

166 Cancer of the Endometrial Treatment Guideline Stage IA G1-2 (<50% myometrial invasion LSVI(-),tum<2cm) Observe Incomplete surgical staged Radiologic image Negative Observation vaginal brachytherapy+pelvic RT Stage IA G1-2 ( LSVI(+),tum>2cm) Stage IA G3 Stage IB Stage II Suspicious/Positive Surgical restaging pathologic Conirmation of metastaic disease Adjuvant treatment f complete surgically staged E-13

167 Cancer of the Endometrial Treatment Guideline Observe Biopsy:.Papillary serous carcinoma.clear cell carcinoma.carcinosarcoma Completely surgical staging as ovarian cancer:.ath+bso.omentectomy.peritoneal biospy.pelvic lymphadenectomy Stage IA Chemotherapy ± brady Tum-directed radiotherapy + brady.para-atic lymphadenectomy Stage IB.Maximal tum debulking Stage II Chemotherapy ± EBRT Stage III ±vaginal brachytherapy Stage IV E-14

168 分期 Cpus Uteri- Carcinoma and Carcinosarcoma Definition of Primary Tum (T) T Categy FIGO Stage T Criteria TX Primary tum cannot be assessed T0 No evidence of primary tum T1 I Cervical carcinoma confined to the cpus uteri, including endocervical glandular involvement T1a IA Tum limited to the endometrium invading less than half the myometrium T1b IB Tum invading one half me of the myometrium T2 II Tum invading the stromal connective tissue of the cervix but not extending beyond the uterus. Dose NOT include endocervical glandular involvement. T3 III Tum involving serosa, adnexa, vagina, parametrium T3a IIIA Tum involving the serosa and/ adnexa (direct extension metastasis) T3b IIIB Vaginal involvement (direct extension metastasis) parametrial involvement T4 IVA Tum invading the bladder mucosa and/ bowel mucosa (bullous edema is not sufficient evidence to classify a tum as T4) Definition of Regional Lymph Node (N) N Categy FIGO Stage N Criteria NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N0(i+) Isolated tum cells in regional lymph node(s) no greater than 0.2 mm N1 IIIC1 Regional lymph node metastasis to pelvic lymph nodes N1mi IIIC1 Regional lymph node metastasis (greater than 0.2 mm but not greater than 2.0 mm in diameter) to pelvic lymph nodes N1a IIIC1 Regional lymph node metastasis (greater than 2.0 mm in diameter) to pelvic lymph nodes N2 IIIC2 Regional lymph node metastasis to para-atic lymph nodes, with without positive pelvic lymph nodes N2mi IIIC2 Regional lymph node metastasis (greater than 0.2 mm but not greater than 2.0 mm in diameter) to para-atic E-15

169 lymph nodes, with without positive pelvic lumph nodes N2a IIIC2 Regional lymph node metastasis (greater than 2.0 mm in diameter) to para-atic lymph nodes, with without positive pelvic lymph nodes Gestational Trophoblastic Neoplasms Definition of Distant Metastasis(M) M Categy FIGO Stage M Criteria M0 No distant metastasis M1 IVB Distant metastasis (includes metastasis to inguinal lymph nodes, intraperitoneal disease, lung, liver, bone ) (It excludes metastasis to pelvic para-atic lymph nodes, vagina, uterine serosa, adnexa). Definition of Primary Tum (T) T Categy FIGO Stage T Criteria TX Primary tum cannot be assessed T0 No evidence of primary tum T1 I Tum confined to uterus T2 II Tum extends to other genital structures (ovary, tube, vagina, broad ligaments) by metastasis direct extension Definition of Distant Metastasis(M) M Categy FIGO Stage M Criteria M0 No distant metastasis M1 Distant metastasis M1a III Lung metastasis M1b IV All other distant metastases E-16

170 參考文獻 1.Cervical Cancer NCCN V from 2. NCCN Clinical Practice Guidelines in OncologyTM Ovarian Cancer (version ).2015 National Comprehensive Cancer Netwk,Inc. 3. Int J Gynecol Cancer May;22(4): Weekly paclitaxel-carboplatin regimen in patients with primary advanced recurrent endometrial carcinoma 4. Miller D, Filiaci V, Fleming G, et al. Randomized phase III noninferiity trial of first line chemotherapy f metastatic recurrent endometrial carcinoma: a Gynecologic Oncology Group study [abstract]. Gynecol Oncol 2012;125:771.

171 Cancer of the Ovarian Treatment Guideline KMHK 原訂日期 :97 年 1 月 1 日 修訂日期 : 年 6 月 5 日

172 卵巢癌修訂紀錄 修訂日期 修訂內容摘要 修訂頁次 版本 106 年 卵巢癌診療指引新制訂 年新增卵巢癌治療前檢查之必要檢查家族史及新增選擇性檢查 TPA LDH E 年 Suspicious Pelvic mass 修改 Wk Up 檢查項目 Pathologic staging stage Ia Ib 增加 Grade 3 clear cell E-20 E Clinical trial supptive care only recurrence therapy 治療增加 (1)complete remission and relapse<6 months after stopping chemotherapy (2)stage II,III and IV with partial response (3)progression following recurrence therapy f latinum-sensitive disease E-23 新增 Ovarian bderline epithelial tum 診療指引 E-25

173 Cancer of the Ovarian Pretreatment 卵巢癌治療前檢查 必要檢查 : 1. 病史及理學檢查 家族史 2. ( 血液常規 ) 全血球計數 ; 常規生化檢驗 3. 婦產科超音波檢查 4. 腹部及骨盆電腦斷層或核磁共振檢查 5. 胸部 X 光 6. 血清腫瘤標記檢驗 :CA-125 選擇性檢查 : 1. 血清腫瘤標記檢驗 :CA-129.CEA 2. 如年齡 <35 歲 :AFP.B-HCG TPA LDH 3. 腹部超音波檢查 4. 膀胱或直腸鏡檢 5. 正子攝影 6. 腹水或腫瘤組織細針穿刺採樣 E-19