Non-Small Cell Lung Cancer Clinical Practice Guideline
PATHOLOGIC DIAGNOSIS OF NSCLC Non-Small Cell Lung Cancer (NSCLC) INITIAL EVALUATION Pathology review H&P (include perfmance status + weight loss) CBC/DC; SMAC Hepatitis profile Smoking cessation Chest CT and Abd echo Options (1) Bronchoscopy (2) Pul function (3) Chest MRI (4) PET-CT (5) Bone scan (6) Brain image CLINICAL STAGE Stage IA, peripheral c (T1ab, N0) Mediastinal CT negative (lymph nodes <1 cm) Stage I, peripheral c (T2a, N0); central c (T1ab-T2a, N0); Stage II (T1ab-T2ab, N1; T2b, N0); stage IIB (T3, N0) d Mediastinal CT negative (lymph nodes <1 cm) Stage IIB e (T3 invasion, N0); Stage IIIA e (T4 extension, N0-1; T3, N1) Stage IIIA e (T1-3, N2) Separate pulmonary nodule(s) (Stage IIB, IIIA, IV) Multiple lung cancers Stage IIIB e (T1-3, N3) mediastinal CT positive Contralateral (lymph nodes 1 cm) palpable supraclavicular lymph nodes Stage IIIB e (T4 extension, N2-3) on CT Stage IV (M1a) (pleural pericardial effusion) Stage IV (M1b) Solitary metastasis with resectable lung lesion Stage IV (M1b) Disseminated metastases NSCL-1
PRETREATMENT EVALUATION f CLINICAL ASSESSMENT Stage IA (peripheral T1ab, N0) PFTs (if not previously done) Bronchoscopy (intraoperative preferred) Pathologic mediastinal lymph node evaluation g (categy 2B) PET/CT scan h (if not previously done) Negative mediastinal nodes Positive mediastinal nodes Operable Medically inoperable See Initial Treatment and Adjuvant Treatment Definitive RT SABR i See Stage IIIA Stage IIIB Stage IB (peripheral T2a, N0) Stage I (central T1ab T2a, N0) Stage II (T1ab 2ab, N1; T2b, N0) Stage IIB (T3, N0) d PFTs (if not previously done) Bronchoscopy Pathologic mediastinal lymph node evaluation g PET/CT scan h (if not previously done) Brain MRI (Stage II, Stage IB [categy 2B]) Negative mediastinal nodes Positive mediastinal nodes Operable Medically inoperable See Initial Treatment and Adjuvant Treatment Definitive RT ± chemotherapy j See Stage IIIA Stage IIIB Note: Clini c a l s t a g e I A - I I B( T 3, N 0) 轉醫學中心執行縱膈腔淋巴結切片, 並評估是否可以進行手術切除如無法手術切除, 則轉回本院進行 Definitive RT ± chemotherapy NSCL-2
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 lymph node dissection systematic lymph node sampling Stage IB (T2a, N0); Stage IIA (T2b, N0) Stage IIA (T1ab-T2a, N1) Stage IIB (T3, N0; T2b, N1) Stage IIIA (T1-3, N2; T3, N1) Margins negative (R0) Margins positive (R1, R2) Margins negative (R0) Margins positive (R1, R2) Margins negative (R0) Margins positive (R1, R2) Observe Chemotherapy in high-risk patients Reresection (preferred) ± chemotherapy RT i,j ± chemotherapy j,p (chemotherapy f stage IIA) Chemotherapy Reresection + chemotherapy Chemadiation + chemotherapy Chemotherapy + RT Chemadiation + chemotherapy Surveillance Note: clinical stage IA IIIA 術後依病理報告, 決定 : (1) 觀察 ;(2) R/T;(3)C/T;(4)CCRT NSCL-3
CLINICAL ASSESSMENT PRETREATMENT EVALUATION CLINICAL EVALUATION Superi sulcus tum See Treatment (NSCL-5) Stage IIB (T3 invasion, N0) Stage IIIA (T4 extension, N0-1; T3, N1) Optional wk-up: PFTs (if not previously done) Bronchoscopy Pathologic mediastinal lymph node evaluation Brain MRI MRI of spine + thacic inlet f superi sulcus lesions abutting the spine subclavian vessels PET/CT scan (if not previously done) Chest wall Proximal airway mediastinum See Treatment (NSCL-5) See Treatment (NSCL-5) Unresectable disease See Treatment (NSCL-5) Metastatic disease See Treatment f Metastasis solitary site (NSCL-12) distant disease (NSCL-14) Note: clinical stage IIB (T3 invasion,n0); stage IIIA ( T4 invasion,n0-1; T3,N1) 的病患原則上皆先執行 (1) Definite R/T (2) C/T (3) CCRT 再行評估是否可做手術切除 接續下頁 NSCL-4
CLINICAL PRESENTATION Superi sulcus tum (T3 invasion, N0-1) Superi sulcus tum (T4 extension, N0-1) Chest wall, proximal airway mediastinum (T3 invasion, N0-1 T4 extension, N0-1) Marginally resectable Unresectable INITIAL TREATMENT Preoperative concurrent chemadiation Preoperative concurrent chemadiation Definitive concurrent chemadiation Surgery (preferred) Concurrent chemadiation Chemotherapy Surgical reevaluation Resectable unresectsble Margins negative (R0) ADJUVANT TREATMENT Surgery + chemotherapy Surgery + chemotherapy Complete definitive RT + chemotherapy Chemotherapy if not given as initial treatment Surveillance (NSCL-13) Reresection + chemotherapy if not Surgery given as initial treatment Margins positive (R1, R2) Chemadiation+ chemotherapy if not given as initial treatment Stage IIIA (T4, N0-1) Definitive concurrent Surveillance Unresectable chemadiation (NSCL-13) Note: 延續上頁 clinical stage IIB (T3 invasion,n0); stage IIIA ( T4 invasion,n0-1; T3,N1) 的病患原則上皆先執行 (1) Definite R/T (2) C/T (3) CCRT 再行評估是否可做手術切除如果無法手術切除, 則繼續完成先前之化 放療 ; 如果可以手術切除, 則於術後接受化療 NSCL-5
CLINICAL ASSESSMENT PRETREATMENT EVALUATION MEDIASTINAL BIOPSY FINDINGS AND RESECTABILITY Stage IIIA (T1 3, N2) Options: PFTs Bronchoscopy Pathologic mediastinal lymph node evaluation PET/CT scan Brain MRI N2, N3 nodes negative N2 nodes positive N3 nodes positive Metastatic disease See Treatment T 1-3, N0-1 (NSCL-7) See Treatment (NSCL-7) See Stage IIIB (NSCL-10) See Treatment f Metastasis solitary site (NSCL-12) distant disease (NSCL-14) Separate pulmonary nodule(s) (Stage IIB, IIIA, IV) Options: PFTs (if not previously done) Bronchoscopy Pathologic mediastinal lymph node evaluation Brain MRI PET/CT scan (if not previously done) Separate pulmonary nodule(s), same lobe (T3, N0) ipsilateral non-primary lobe (T4, N0) Stage IV (N0, M1a): Contralateral lung (solitary nodule) Extrathacic metastatic disease See Treatment (NSCL-8) See Treatment (NSCL-8) See Treatment f Metastasis solitary site (NSCL-12) distant disease (NSCL-14) Note: 轉醫學中心執行縱膈腔淋巴結切片, 並評估是否可以進行手術切除 如無法手術切除, 則轉回本院進行 Definitive RT ± chemotherapy NSCL-6
MEDIASTINAL BIOPSY FINDINGS INITIAL TREATMENT ADJUVANT TREATMENT T1-3, N0-1 (including T3 with multiple nodules in same lobe) Surgery Resectable Unresectable Surgical resection + mediastinal lymph node dissection systematic lymph node sampling See Treatment accding to clinical stage (NSCL-1) N0 1 N2 Margins negative (R0) Margins positive (R1, R2) n See NSCL-3 Chemotherapy + RT Chemadiation n + chemotherapy T1-2, T3 ( 7 cm), N2 nodes positive k Brain MRI PET/CT scan, if not previously done Negative f M1 disease Positive Definitive concurrent chemadiation No apparent Surgery Induction chemotherapy ± RT See Treatment f Metastasis solitary site (NSCL-12) distant disease (NSCL-14) progression Progression Local Systemic ± chemotherapy ± RT(if not given) RT(if not given) ± chemotherapy See Treatment f Metastasis solitary site (NSCL-12) distant disease (NSCL -14) T3 (invasion), N2 nodes positive Brain MRI PET/CT scan, if not previously done Negative f M1 disease Positive Definitive concurrent chemadiation See Treatment f Metastasis solitary site (NSCL-12) distant disease (NSCL-14) n The panel recommends concurrent chemadiation f R2 resections and sequential chemadiation f R1 resection NSCL-7 Note: 轉醫學中心執行縱膈腔淋巴結切片, 並評估是否可以進行手術切除
CLINICAL PRESENTATION N0 1 See NSCL-3 f T3 NSCL-5 f T4 Separate pulmonary nodule(s), same lobe (T3, N0) ipsilateral non-primary lobe (T4, N0) Stage IV (N0, M1a): Contralateral lung (solitary nodule) Surgery N2 Treat as two primary lung tums if both curable Margins negative (R0) Margins positive (R1, R2) n See Evaluation (NSCL-1) Chemotherapy + RT Chemadiation n + chemotherapy Surveillance (NSCL-13) Surveillance (NSCL-13) Suspected multiple lung cancers (based on the presence of biopsyproven synchronous lesions histy of lung cancer) Chest CT with contrast PET-CT scan (if not previously done) Brain MRI Disease outside of chest No disease outside of chest See Systemic Therapy f Metastatic Disease (NSCL-15) Pathologic mediastinal lymph node g evaluation See Systemic Therapy N2-3 f Metastatic Disease (NSCL-15) N0-1 See Initial Treatment (NSCL-9 ) n The panel recommends concurrent chemadiation f R2 resections and sequential chemadiation f R1 resections. NSCL-8
CLINICAL PRESENTATION INITIAL TREATMENT Low risk of becoming symptomatic Observation Surveillance (NSCL-13) Multiple lesions Multiple lung cancers Asymptomatic Solitary lesion (metachronous disease) High risk of becoming symptomatic Definitive local therapy possible Parenchymal sparing resection (preferred) Radiation Ablation Symptomatic Definitive local therapy not possible Consider palliative chemotherapy ± local palliative therapy See Systemic Therapy f Metastatic Disease (NSCL-15) I See Principles of Radiation Therapy (NSCL-B). NSCL-9
CLINICAL ASSESSMENT PRETREATMENT EVALUATION INITIAL TREATMENT Stage IIIB (T1 3, N3) PFTs (if not previously done) PET/CT scan (if not previously done) Brain MRI Pathologic confirmation of N3 disease by either: (optional) Mediastinoscopy Supraclavicular lymph node biopsy Thacoscopy Needle biopsy Mediastinotomy EUS/EBUS Bx N3 negative N3 positive Metastatic disease See Initial treatment f stage I IIIA (NSCL-7) Definitive concurrent chemadiation s See Treatment f Metastasis solitary site (NSCL-12) distant disease (NSCL-14) s If full-dose chemotherapy is not given concurrently with RT as initial treatment, give additional 4 cycles of full-dose chemotherapy. NSCL-10
CLINICAL ASSESSMENT Stage IIIB (T4 extension, N2 3) PRETREATMENT EVALUATION PET/CT scan (if not previously done) Brain MRI Pathologic confirmation of N2 3 disease by either: (optional) Mediastinoscopy Supraclavicular lymph node biopsy Thacoscopy Needle biopsy Mediastinotomy EUS/EUBS Bx Contralateral mediastinal node negative Contralateral mediastinal node positive (T4, N3) Metastatic disease Ipsilateral mediastinal node negative (T4, N0-1) Ipsilateral mediastinal node positive (T4, N2) INITIAL TREATMENT See Treatment f Stage IIIA (NSCL-7) Definitive concurrent chemadiation s Definitive concurrent chemadiation s See Treatment f Metastasis solitary site (NSCL-12) distant disease (NSCL-14) Stage IV, M1a: pleural pericardial effusion Thacentesis pericardiocentesis ± thacoscopy if thacentesis indeterminate Negative Positive See Treatment accding to TNM stage (NSCL-7) Local therapy if necessary (eg, pleurodesis, ambulaty small catheter drainage, pericardial window) + treatment as f stage IV disease (NSCL-12) s If full-dose chemotherapy is not given concurrently with RT as initial treatment, give additional 4 cycles of full-dose chemotherapy. NSCL-11
CLINICAL ASSESSMENT Stage IV, M1b: solitary site PRETREATMENT EVALUATION Pathologic mediastinal lymph node evaluation Bronchoscopy Brain MRI PET/CT scan (if not previously done) Brain y Adrenal Pathologic diagnosis by needle resection INITIAL TREATMENT Surgical resection, followed by whole brain RT (WBRT) (categy 1) stereotactic radiosurgery (SRS) SRS + WBRT (categy 1 f one metastasis) SRS alone T1-2, N0-1; T3, N0 Local therapy f adrenal T1-2, N2; lesion (if lung lesion curable, T3, N1-2; based on T and N stage) Any T, N3; T4, Any N See Systemic Therapy f Metastatic Disease (NSCL-15) Surgical resection of lung lesion Stereotactic ablative radiotherapy (SABR) of lung lesion Chemotherapy Chemotherapy Surgical resection of lung lesion See Systemic Therapy f Metastatic Disease (NSCL-15) NSCL-12
SURVEILLANCE Non-small cell lung cancer Guideline, version 2 2013/05 Locegional recurrence See Therapy f Recurrence and Metastasis (NSCL-14) No evidence of clinical/radiographic disease), stages I-IV: H&P and chest CT ± contrast every 6-12 mo f 2 y (categy 2B), then H&P and a non-contrastenhanced chest CT annually (categy 2B) Smoking cessation advice, counseling, and pharmacotherapy PET brain MRI is not indicated See Cancer Survivship Care (NSCL-G). Distant metastases See Therapy f Recurrence and Metastasis (NSCL-14) NSCL-13
THERAPY FOR RECURRENCE AND METASTASIS Non-small cell lung cancer Guideline, version 2 2013/05 Endobronchial obstruction Laser/stent/other surgery External-beam RT brachytherapy Photodynamic therapy Locegional recurrence Resectable recurrence Mediastinal lymph node recurrence Reresection (preferred) External-beam RT SABR Concurrent chemadiation (if RT not previously given) No evidence of disseminated disease Observation Systemic chemotherapy (categy 2B) Superi vena cava (SVC) obstruction Concurrent chemadiation (if not previously given) External-beam RT SVC stent Evidence of disseminated disease See Systemic Therapy f Metastatic Disease (NSCL-15) Severe hemoptysis External-beam RT brachytherapy Laser photodynamic therapy embolization Surgery Localized symptoms Palliative external-beam RT Distant metastases Diffuse brain metastases Bone metastasis Palliative external-beam RT Palliative external-beam RT + thopedic stabilization, if risk of fracture Consider bisphosphonate therapy denosumab See Systemic Therapy f Metastatic Disease (NSCL-15) Solitary metastasis See pathway f Stage IV, M1b, solitary site (NSCL-12) Disseminated metastases See Systemic Therapy f Metastatic Disease (NSCL-15) i NSCL-14
SYSTEMIC THERAPY FOR METASTATIC DISEASE --- HISTOLOGIC SUBTYPE EGFR mutation ALK negative See First-Line Therapy (NSCL-16) Adenocarcinoma Large Cell NSCLC NOS EGFR mutation testing ALK testing EGFR mutation positive See First-Line Therapy (NSCL -17) Metastatic Disease Establish histologic subtype with adequate tissue f molecular testing Smoking cessation counseling ALK positive See First-Line Therapy (NSCL-17) Squamous cell carcinoma EGFR mutation and ALK testing are not routinely recommended except in never smokers and small biopsy specimens ee See First-Line Therapy (NSCL -18) NSCL-15
. ADENOCARCINOMA, LARGE CELL, NSCLC NOS: EGFR MUTATION AND ALK NEGATIVE Non-small cell lung cancer Guideline, version 2 2013/05 FIRST-LINE THERAPY RESPONSE EVALUATION MAINTENANCE THERAPY PS 0-1 PS 2 PS 3-4 Doublet chemotherapy Bevacizumab + chemotherapy (if criteria met) Cisplatin/pemetrexed (if criteria met) Cetuximab/vinelbine/cisplatin Chemotherapy Best supptive care only (See NCCN Guidelines f Palliative Care) Tum response evaluation Progression Tum response stable disease 4-6 cycles (total) Tum response evaluation See Second-line Therapy (NSCL-19) Progression Tum response Continuation of current regimen until disease progression Continuation maintenance bevacizumab cetuximab pemetrexed bevacizumab + pemetrexed NSCL-16
ADENOCARCINOMA, LARGE CELL, NSCLC NOS: EGFR MUTATION OR ALK POSITIVE FIRST-LINE THERAPY EGFR mutation positive EGFR mutation discovered pri to first-line chemotherapy EGFR mutation discovered during first-line chemotherapy Erlotinib Switch maintenance: erlotinib May add erlotinib to current chemotherapy Progression Progression Symptomatic Asymptomatic Brain Systemic Isolated lesion Multiple lesions Isolated lesion Multiple lesions Consider local therapy and continue erlotinib Consider WBRT and continue erlotinib Consider local therapy and continue erlotinib Consider systemic therapy ± erlotinib Continue erlotinib ALK positive Crizotinib Progression See Second-line Therapy (NSCL-19) NSCL-17
SQUAMOUS CELL CARCINOMA FIRST-LINE THERAPY RESPONSE EVALUATION MAINTENANCE THERAPY PS 0-1 Doublet chemotherapy Cetuximab/vinelbine/ cisplatin Tum response evaluation Progression See Second-line Therapy (NSCL-19) Progression PS 2 Chemotherapy Tum response stable disease PS 3-4 Best supptive care 4-6 cycles (total) Tum response evaluation Tum response stable disease Continuation of current regimen until disease progression Continuation maintenance cetuximab gemcitabine Switch maintenance erlotinib docetaxel Close observation NSCL-18
ADENOCARCINOMA, LARGE CELL, NSCLC NOS, SQUAMOUS CELL CARCINOMA SECOND-LINE THERAPY THIRD-LINE THERAPY Perfmance status 0-2 Docetaxel Pemetrexed (nonsquamous) Erlotinib Platinum doublet ± bevacizumab (if erlotinib crizotinib given as first-line and nonsquamous histologic type) Progression Perfmance status 0-2 Perfmance status 3-4 If not already given: Docetaxel Pemetrexed (nonsquamous) Erlotinib Erlotinib Progression Best supptive care only Perfmance status 0-2 Perfmance status 3, 4 Best supptive care Clinical trial Best supptive care only Perfmance status 3-4 Erlotinib Best supptive care only SCL-19
CHEMOTHERAPY REGIMENS Non-small cell lung cancer Guideline, version 2 2013/05 癌別 :Non-small cell lung cancer Adjuvant 最近改版日期 2013/05 (1) Alimta ± Cisplatin regimen (every 21 days) -Alimta 500 mg/m2 IVD D1 -Cisplatin 50-100 mg/m2 IV D1 (2)Gemcitabine ± Cisplatin regimen (every 28 days) -Gemcitabine 1000mg/m2 IVD D1,8,15 -Cisplatin 50-100 mg/m2 IV D15 (3) Taxotere ± Cisplaitn regimen (every 28 days) -Taxotere 30-35 mg/m2 IV D1,8,15 處方內容 -Cisplatin 50-100 mg/m2 IV D15 (4) Taxol ± Cisplatin regimen (every 28 days) -Taxol 60-80 mg/m2 IV D1,8,15 -Cisplatin 50-100 mg/m2 IV D15 (5) Navelbine ± Cisplaitn regimen(every 28 days) -Navelbine 25-30 mg/m2 IVD1,8,15 Oral Navelbine 60mg/m2 D1,8,15 -Cisplatin 50-100mg/m2 IV D15 Neoadjuvant 最近改版日期 2013/05 (1) Alimta ± Cisplatin regimen (every 21 days) -Alimta 500 mg/m2 IVD D1 -Cisplatin 50-100 mg/m2 IV D1 (2)Gemcitabine ± Cisplatin regimen (every 28 days) -Gemcitabine 1000mg/m2 IVD D1,8,15 -Cisplatin 50-100 mg/m2 IV D15 (3) Taxotere ± Cisplaitn regimen (every 28 days) -Taxotere 30-35 mg/m2 IV D1,8,15 處方內容 -Cisplatin 50-100 mg/m2 IV D15 (4) Taxol ± Cisplatin regimen (every 28 days) -Taxol 60-80 mg/m2 IV D1,8,15 -Cisplatin 50-100 mg/m2 IV D15 (5) Navelbine ± Cisplaitn regimen(every 28 days) -Navelbine 25-30 mg/m2 IVD1,8,15 Oral Navelbine 60mg/m2 D1,8,15 -Cisplatin 50-100mg/m2 IV D15
CCRT 最近改版日期 2013/05 (1) Monotherapy : - weekly Gemcitabine 300-500mg/M2 (2) Combination: 處方內容 - weekly (Gemcitabine 300mg/M2 + Cisplatin20mg/M2 )