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Chung Shan Medical University Hospital 肺癌治療指引 Clinical Guideline 2012 version 6.0
中中 山山 醫醫 學學 大大 學學 附附 設設 醫醫 院院
肺肺 癌癌 診診 療療 指指 引引
本臨床指引參考台灣國家衛生研究院、與美國NCCN版本
肺癌多專科醫療團隊編修
癌症委員會主任委員 癌症委員會執行長 癌症防治中心主任 團隊負責人
2018/01/11Version12.0
2016/12/15Version11.0
2015/11/24 Version10.0
2014/12/09 Version 9.0 2013/12/24 Version 8.0
2012/12/11 Version 7.0
2012/01/03 Version 6.0 2010/08/05 Version 5.0
2009/12/15 Version 4.0
2008/05/27 Version 3.0
2008/02/05 Version 2.0 2007/11/13 Version 1.0
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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FINDINGS FOLLOW-UP
Incidental
finding: solid
nodule(s)
on chest CT
Low risk
High risk
8 mm
6–8 mm
No routine follow-up
CT at 6–12 mo Stable Consider CT
at 18–24 mo
Consider CT at 3 mo,
PET/CT, or biopsy
8 mm
CT at 6–12 mo
(optional) Stable No routine
follow-up
CT at 6–12 mo Stable Repeat CT at 18–24 mo
Consider CT at 3 mo,
PET/CT, or biopsy
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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FINDINGS FOLLOW-UP
Incidental
finding:
subsolid
nodule(s)
on chest CT
Solitary pure
ground-glass
nodules
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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目錄 一、非小細胞肺癌治療指引………………………………………………………………………………………………………………P4
二、小細胞肺癌治療指引…………………………………………………………………………………………………………………P28
三、肺癌輔助化學治療……………………………………………………………………………………………………………………P35
四、肺癌化學治療和胸部放射線治療……………………………………………………………………………………………………P38
五、射頻燒灼術(RFA)的適應症 …………………………………………………………………………………………………………P40
六、安寧緩和照護原則……………………………………………………………………………………………………………………P41
七、參考文獻………………………………………………………………………………………………………………………………P41
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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非小細胞肺癌治療指引
DIAGNOSIS INITIAL EVALUATION CLINICAL STAGE
H&P (include
performance status
+ weight loss)
cessation
Counseling(optional)
Non-Small
Cell Lung
Cancer
(NSCLC)
See Pretreatment Evaluation (Page 3)
Stage IA, peripheral b (T1abc, N0)
Mediastinal CT (lymph nodes < 1 cm)
Stage IIB d (T3 invasion, N0) c,
Stage IIIA d (T4 extension, N0-1; T3, N1)
Stage IVA (M1b) Limited metastasis with respectable lung lesion sites and definitive therapy
For thoracic disease feasible
Stage IB, peripheralb ( T2a,N0); centralb( T1abc-T2a, N0) Stage II (T1abc-T2ab, N1;T2b,N0); Stage IIB(T3,N0) c ;StageIIIA(T3,N1) Mediastinal CT (lymph nodes < 1 cm)
Stage IIIA d (T1-3, N2) Stage IIIB (T3,N2)
Separate pulmonary nodule(s) (Stage IIB, IIIA, IV)
Multiple Lung Cancers
Stage IIIB d (T1-2, N3); Stage IIIC(T3,N3)mediastinal CT positive Contralateral (lymph nodes ≥ 1 cm) or palpable
supraclavicular lymph nodes
Stage IIIB d (T4 extension, N2-3) on CT Stage IIIC(T4,N3)
Stage IVA (M1a) (pleural or pericardial effusion) e
Stage IVB (M1bc) Disseminated metastasis
See Pretreatment Evaluation (Page 12)
See Pretreatment Evaluation (Page 12)
See Pretreatment Evaluation (Page 13)
See Pretreatment Evaluation (Page 12)
See Pretreatment Evaluation (Page 11)
See Pretreatment Evaluation (Page 3)
See Pretreatment Evaluation (Page 5)
See Pretreatment Evaluation (Page 7)
See Pretreatment Evaluation (Page 7) See Pretreatment Evaluation (Page 9) aSee Principles of Pathological Review (NSCL-A).
bBased on the CT of the chest: Peripheral = outer half of lung. Central = inner (central) half of lung. c T3, N0 related to size or satellite nodules. d For patients considered to have stage IIB and tumors, where more than one treatment modality (surgery, radiation therapy. or chemotherapy) is usually considered, a multidisciplinary evaluation should be performed e Most pleural effusions associated with lung cancer are due to tumor. There are few patients in whom multiple cytopathologic examinations of pleural fluid are negative for tumor and fluid is non-blood and not an exudate. When these elements and clinical judgment dictate the effusion is not related to the tumor, the effusion should be for excluded as a staging element. Pericardial effusion is classified using the same criteria. Note: All recommendations are category 2A unless otherwise indicated.
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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CLINICAL
ASSESSMENT
PRETREATMENT EVALUATION
c T3,N0 related to size or satellite nodules.
d Positive PET scan findings need pathologic or other radiologic confirmation.
*Optional;
# See RT guideline
Stage IA
(peripheral T1abc, N0)
Stage IB
(peripheral T2a, N0)
Stage I (central T1abc-T2a,
N0)
Stage II (T1abc-2ab,
N1;T2b,N0)
Stage IIB (T3, N0) c
Stage IIIA (T3, N1)
PFTs (if not previously done)
Bronchoscopy *
Mediastinoscopy (category 2B) *
Thoracoscopy *
PET /CT scan d *
Negative
mediastinal
nodes
See Initial Treatment
and Adjuvant Treatment (Page 4)
Definitive RT including
Stereotactic ablative RT(SABR)
See
Stage IIIA /IIIB(Page 7) or
Stage IIIB/IIIC (Page 11)
Medically
inoperable
Positive
mediastinal
nodes
PFTs (if not previously done)
Mediastinoscopy *
Thoracoscopy* PET /CT scan d *
Brain CT/MRI *
(Stage II, IIIA) (Stage IB [optional])
Durvalumab
Note: All recommendations are category 2A unless otherwise indicated.
Negative
mediastinal
nodes
Positive
mediastinal
nodes
Resectable
Medically
inoperable
See Initial Treatment
and Adjuvant Treatment (Page 4)
N0
N1
Definitive
RT including
SABR
Definitive
chemoradiation
Consider adjuvant
chemotherapy
(category 2B) for high- risk stages IB-IIB
Resectable
See
Stage IIIA /IIIB(Page 7) or
Stage IIIB/IIIC (Page 11)
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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INITIAL TREATMENT FIDINGS AT SURGERY ADJUVANT TREATMENT
Surgical Exploration e and resection
Stage IA
(T1abc, N0)
Stage IB T2a, N0 Stage IIA
(T2b, N0)
Stage IIB (T1abc-2a; N1) Stage IIB
(T3, N0; T2b, N1)
Stage IIIA (T1-2,N2;T3,N1)
Stage IIIB(T3,N2)
Margins
Negative (R0)
Margins positive
(R1, R2) f
Margins
Negative (R0) f
Margins positive (R1, R2) f
Margins
Negative (R0) f
Margins positive
(R1, R2) f
Mediastinal lymph node
dissection
Observe or
Chemotherapy (category 2B) in high risk patients h
Reresection or Concurrent or Sequential Chemoradiatiotherapy i or UFT or Chemotherapy or
Radiotherapy i
Follow up or UFT v Chemotherapy (category 2B) in high risk patients h
Reresection + chemotherapy j or Chemotherapy and / or Radiotherapy
Chemotherapy (category 1) j
Chemotherapy (category 1) j or
Chemotherapy and / or Radiotherapy i j (category 2B)
Resection + chemotherapy j or
Chemotherapy and / or Radiotherapy i j
Chemotherapy (category 1) ± Mediastinal Radiotherapy i
or RT i + chemotherapy j (category 2B)
No adverse factors g
Adverse factors g
Margins negative
(R0) f
Margins positive (R1, R2) f
Chemotherapy and /or radiotherapy i
e See Principles of Surgical Resection (Page 19).
f R0=no residual tumor, R1=microscopic residual tumor, R2=macroscopic residual tumor.
g Adverse factors include: inadequate mediastinal lymph node dissection, extracapsular spread, multiple positive hilar nodes, close margins. h High risk patients is defined as poorly differentiated tumor, lymphatic or/and vascular invasion, wedge resection, minimal ma rgins. i See RT Guideline. j See Principles of Systemic Therapy for Non-Small Cell Lung Cancer (Page 20). v As adjuvant chemotherapy and pathology confirm with NSCLC adenocarcinoma and tumor should to be equal or bigger than 3 cm (T2) and limit to take for 2 years.
Note: All recommendations are category 2A unless otherwise indicated.
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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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 * Mediastinoscopy*
Brain CT/MRI*
MRI of spine + thoracic inlet for Superior sulcus lesions
abutting the spine or
subclavian vessels*
PET scan d *
Superior sulcus tumor
Chest wall
Proximal airway
or mediastinum
Metastatic disease See Treatment for Metastasis (Page 13)
Treatment (Page 6)
Treatment (Page 6)
Treatment (Page 6)
d Positive PET scan findings need pathologic or other radiologic confirmation.
* Optional
Note: All recommendations are category 2A unless otherwise indicated.
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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CLINICAL PRESENTATION INITIAL TREATMENT ADJUVANT
TREATMENT
Concurrent or Sequential
chemoradiation i,l
Superior sulcus tumor k
(T3 invasion,
N0-1)
Superior sulcus
tumor k
(T4 extension,
N0-1)
Chest wall,
proximal airway or mediastinum
(T3 invasion, N0-1;
Resectable T4,
extension, N0-1)
Marginally
Resectable e
Unresectable
Concurrent or Sequential
chemoradiation i
Definitive concurrent or Sequential
chemoradiation i
Surgery e (preferred)
or
Chemotherapy or
Concurrent
or Sequential chemoradiation i
Surgery e
Margins negative
(R0) f
Margins positive
(R1, R2) f
Resectable
Unresectable
Surgical
reevaluation m
Surgery + chemotherapy
Surgery + chemotherapy
Complete definitive RT i +
chemotherapy j
Chemotherapy j
Reresection + chemotherapy j
or Chemotherapy and /or
Radiotherapy i + chemotherapy j
e See Principles of Surgical Resection (Page 19). f R0=no residual tumor, R1=microscopic residual tumor, R2=macroscopic residual tumor.
i See RT guideline.
j See Principles of Systemic Therapy for Non-Small Cell Lung Cancer (Page 20).
k It is difficult to distinguish between T3 and T4 superior sulcus tumors.
l Rusch VW, Giroux DJ, Kraut MJ, et al. Induction chemoradiation and surgical resection for non-small cell lung carcinomas of the superior sulcus:
Initial results of the Southwest Oncology Group trial 9416 (Intergroup trial 0160). J Thorac Cardiovasc Surg 2001; 121(3):472-483.
m RT should continue to definitive dose without interruption if patient is not a surgical candidate.
Note: All recommendations are category 2A unless otherwise indicated.
Stage IIIA (T4, N0-1)
Unresectable
Definitive concurrent
chemoradiation (category 1)
Durvalumab
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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CLINICAL
ASSESSMENT
PRETREATMENT EVALUATION MEDIASTINAL BIOPSY FINDINGS
AND RESECTABILITY
Separate pulmonary
nodules
Stage IIB,
IIIA, IV
Stage ⅢA (T1-2, N2)
Stage IIIB
(T3, N2)
PFTs (if not
previously done)
Bronchoscopy* Pothologic mediastinal
lymph node evaluationh*
Brain CT/MRI*
PET scan i *
PFTs (if not previously
done) Bronchoscopy
Pothologic mediastinal
lymph node evaluationh*
Brain CT/MRI *
Bone scan
PET scan i *
N2, N3 nodes negative
N2 nodes positive
N3 nodes positive
Metastatic disease
Separate pulmonary nodule(s), same lobe (T3, N0-1)
or ipsilateral non-primary lobe (T4, N0-1)
Stage IV (N0, M1a): Contralateral lung
(solitary nodule)
Extrathoracic metastatic disease
See Treatment (Page 8)
See Treatment (Page 8)
See Stage ⅢB (Page 11)
See Treatment for Metastasis(Page 13)
See Treatment (Page 9)
See Treatment (Page 9)
See Treatment for Metastasis (Page 13)
or distant disease (Page 15)
hMethods for evaluation include mediastinoscopy, mediastinotomy and CT-guidebiopsy.
i Positive PET scan findings need pathologic or other radiologic confirmation. If PET scan positive in the
mediastinum, lymph node status needs pathologic confirmation;
*Optional
Note: All recommendations are category 2A unless otherwise indicated.
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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MEDIASTINAL BIOPSY FINDINGS
INITIAL TREATMENT ADJUVANT TREATMENT
T1-3,N0-1
(including T3 with multiple
nodulesin
same lobe)
T1-2,
T3(≧7cm) N2 nodes
postivei
T3(invasion), N2 nodes
postive
Brain CT/MRI*
PET scan d (if
not previously
done; considered
if any)
Brain CT/MRI * PET scan d (if not
previously
done; considered
if any)
Resectable
Medically inoperable
Negative for M1 disease
Positive
Negative for
M1 disease
Positive
Surgical resection e + mediastinal
lymph node
dissection
See Treatment according
to clinical stage(Page 2)
Induction
chemotherapy ± RT i
or Definitive concurrent
N0-1
N2
See Initial treatment of M1 disease
(Page 13)
Definitive concurrent or Sequential
chemoradiation i
See Initial treatment of M1 disease
(Page 13)
Margins
negative (R0) f
Margins positive
(R1, R2) f
Chemotherapy j (category 1)
+ RT or Chemotherapy j
Concurrent or Sequential chemoradiation I or
Chemotherapy and / or
Radiotherapy i
See Page(Page 3 or 4)
No
progression
Progression
Surgery
± chemotherapy j (category 2B)
± RT i (if not given)
Chemotherapy and / or Radiotherapy i
d Positive PET scan findings need pathologic or other radiologic confirmation. e See Principles of Surgical Resection (Page 19). f R0=no residual tumor, R1= microscopic residual tumor, R2=macroscopic residual tumor. i Positive PET scan findings need pathologic or other radiologic confirmation. If PET scan positive in the mediastinum, lymph node status needs pathologic confirmation; j See Principles of Systemic Therapy for Non-Small Cell Lung Cancer (Page ).
* Optional
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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CLINICAL PRESENTATION ADJUVANT TRETMENT
Separate pulmonary nodule(s), same lobe (T3, N0-1), or ipsilateral non-primary lobe
(T4, N0-1)
Stage IVA (N0, M1a): Contralateral lung
(solitary nodule)
Suspected multiple lung cancers (based on the presence of biopsy- proven synchronous lesions or history of
lung cancer)v,w
Surgeryj
N0–1
N2
Treat as two primary lung
tumors if both curable
• Chest CT with contrast • PET/CT scan (if not previously done)i
• Brain MRI
See Evaluation (Page 2)
Disease outside
of chest
No disease outside of
chest
Margins negative (R0)q
Margins positiveq
R1q
R2q Concurrent
chemoradiationk,p
Chemoradiationk
(sequentialn or concurrentp)
Sequential chemotherapyn
(category 1) + RTk
Chemotherapyn See (Page 14)
See (Page 14)
See (Page 14)
See (Page 14)
See Systemic Therapy for Metastatic Disease(Page 17)
Pathologic mediastinal lymph node
evaluationh
N0-1
N2-3
See Initial Treatment(Page 10)
See Systemic Therapy for Metastatic
Disease(Page 16)
h Methods for evaluation include mediastinoscopy, mediastinotomy, EBUS, EUS,
and CT-guided biopsy. i Positive PET/CT scan findings for distant disease need pathologic or other
radiologic confirmation. If PET/CT scan is positive in the mediastinum, lymph
node status needs pathologic confirmation. j See Principles of Surgical Therapy (NSCL-B).
k See Principles of Radiation Therapy (NSCL-C).
n See Chemotherapy Regimens for Neoadjuvant and Adjuvant Therapy (NSCL-D).
p See Chemotherapy Regimens Used with Radiation Therapy (NSCL-E).
q
R0 = no residual tumor, R1 = microscopic residual tumor, R2 = macroscopic
residual tumor. v Lesions with different cell types (eg, squamous cell carcinoma, adenocarcinoma)
may be different primary tumors. This analysis may be limited by small biopsy
samples. However, lesions of the same cell type are not necessarily metastases. w
For guidance regarding the evaluation, workup, and management of subsolid
pulmonary nodules, please see the diagnostic evaluation of a nodule suspicious
for lung cancer.
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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CLINICAL PRESENTATION INITIAL TREATMENT
Multiple
lesions
Multiple lung
cancers
Asymptomatic
Symptomatic
Solitary lesion (metachronous
disease)
Low risk of
becoming
symptomaticx
High risk of
becoming
symptomaticx
Observation Surveillance(Page 14)
Parenchymal sparing
resection (preferred)j,y
or Radiationk
or
Ablation
Definitive
local therapy
possible
Definitive local therapy
not possible
Consider palliative chemotherapy ± local
palliative therapy
See Systemic Therapy
for Metastatic Disease
(Page 16)
j See Principles of Surgical Therapy (NSCL-B). k See Principles of Radiation Therapy (NSCL-C). x Lesions at low risk of becoming symptomatic can be observed (eg, small subsolid nodules with slow growth). However, if the lesion(s) becomes symptomatic or becomes high risk for
producing symptoms (eg, subsolid nodules with accelerating growth or increasing solid component or increasing FDG uptake, even while small),treatment should be considered. y Lung-sparing resection is preferred, but tumor distribution and institutional expertise should guide individual treatment planning.
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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CLINICAL
ASSESSMENT
PRETREATMENT EVALUATION INITIAL TREATMENT
N3 negative
Stage IIIB
(T1–2, N3)
Stage IIIC
(T3, N3)
• PFTs (if not previously
done) • PET/CT scan i (if not
previously done)
• Brain MRI
• Pathologic confirmation of N3 disease by either:
Mediastinoscopy
Supraclavicular lymph node biopsy
Thoracoscopy Needle biopsy
Mediastinotomy
N3 positive
Metastatic disease
See Initial treatment for stage I–
IIIA(Page 8)
Definitive concurrent chemoradiationk,p,t
(category 1)
See Treatment for Metastasis limited sites (Page 13) or
distant disease (Page 14)
i Postive PET/CT scan findings for distant disease need pathologic or other radiologic confirmation. If PET/CT scan positive in the mediastinum, lymph node status needs pathologic confirmation.
k See Principles of Radiation Therapy (NSCL-C).
p See Chemotherapy Regimens Used with Radiation Therapy (NSCL-E).
t If full-dose chemotherapy is not given concurrently with RT as initial treatment, give additional 2 cycles of full-dose chemotherapy.
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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CLINICAL
ASSESSMENT
PRETREATMENT EVALUATION INITIAL TREATMENT
PET scand (if not
previously done)
Brain MRI * Pathologic confirmation
of N2-3 disease by
either: Bronchoscopy
(TBNA)
Mediastinoscopy
Supraclavicular lymph node biopsy
Thoracoscopy
Needle biopsy
Mediastinotomy
Stage IIIB
(T4 ,N2) Stage IIIC
(T4,N3)
Stage IVA M1a:
pleural or
pericardial
effusion
Thoracentesis or
pericardiocentesis if indicated ±
thoraccoscopy if
thoracentesis
indeterminate
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)
Negative n
Positive n Local therapy if necessary (eg, pleurodesis, ambulatory small catheter drainage,
pericardial window) + treatment as for stage
IV disease (Page 17)
See Treatment according to TNM stage
See Treatment Stage IIIA (Page 6)
Definitive concurrent chemoradiation i (category 1)
Concurrent chemoradiation i
(category 1)
See Treatment for Metastasis(Page 14)
d Positive PET scan findings need pathologic or other radiologic confirmation. If PET scan positive in the mediastinum, lymph node status needs pathologic confirmation. i See RT guideline. n Most pleural effusions associated with lung cancer are due to tumor. There are few patients in whom multiple cytopathologic examinations of pleural fluid are negative for tumor. Fluid
is non-bloody and not an exudates. When these elements and clinical judgment dictate the effusion is not related to the tumor, the effusion should be excluded as a staging element. Pericardial effusion is classified using the same criteria.
* Optional
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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CLINICAL ASSESSMENT PRETREATMENT EVALUATION INITIAL TREATMENT
Brainbb
Stage IVA, M1b: limited
sitesaa
• Bronchoscopy • Brain MRI • PET/CT scani (if not previously done)
Adrenal
Surgical resection,j followed by whole brain RTk (WBRT) (category 1) or stereotactic radiosurgeryk (SRS) or SRS + WBRTk (category 1 for one metastasis) or
SRSk alone
Local therapy for adrenal lesioncc (if lung lesion curable, based on T and N stage) (category 2B)dd or See Systemic Therapy for
Metastatic Disease (Page 17)
T1-2, N0-1;
T3, N0
T1-2, N2; T3, N1-2; Any T, N3;
T4, Any N
Surgical resection of lung lesionj or SABR of lung lesion or
Chemotherapyee
Chemotherapyee
Surgical resection of lung lesionj or SABR of
lung lesion
See Systemic Therapy for Metastatic Disease
(Page 17)
Pathologic diagnosis by needle or resection
h Methods for evaluation include mediastinoscopy, mediastinotomy, EBUS, EUS, and CT-guided biopsy. i Positive PET/CT scan findings for distant disease need pathologic or other radiologic confirmation. If PET/CT scan is positive in the mediastinum, lymph node status needs
pathologic confirmation. j See Principles of Surgical Therapy (NSCL-B). k See Principles of Radiation Therapy (NSCL-C).
aa Aggressive local therapy may be appropriate for selected patients with limited-site oligometastatic
bb See NCCN Guidelines for Central Nervous System Cancers.
cc May include adrenalectomy or RT (including SABR).
dd Patients with N2 disease have a poor prognosis and systemic therapy should be considered.
eeSee Systemic Therapy for Advanced or Metastatic Disease (NSCL-F).
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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THERAPY FOR RECURRENCE AND METASIS
Locoregional recurrence
Distant
metastases
Endobronchial
obstruction
Resectable recurrence
Mediastinal lymph node recurrence
Superior vena cava
(SVC) obstruction
Severe hemoptysis
Localized symptoms
Diffuse brain metastases
Bone metastasis
Solitary metastasis
Disseminated metastases
No prior RT
Prior RT
Concurrent chemoradiationk,p
Systemic therapyee
• Laser/stent/other surgery j
• External-beam RT or brachytherapy
• Reresection (preferred)j
• External-beam RT or SABRk,l
• Concurrent chemoradiationk,p
(if not previously given) • External-beam RT
k
• External-beam RT or
brachytherapyk
• Embolization
• Surgery
Palliative external-beam RTk
Palliative external-beam RTk,bb
• Palliative external-beam RTk + orthopedic
stabilization, if risk of fracture • Consider bisphosphonate therapy or denosumab
See pathway for Stage IV, M1b, solitary site (Page 13)
See Systemic Therapy for Metastatic Disease (Page 17)
No evidence of disseminated
disease
Evidence of disseminated
disease
Observation or Systemic therapyee
(category 2B)
See Systemic Therapy for Metastatic Disease
(Page 17)
See Systemic Therapy for Metastatic Disease
(Page 17)
j See Principles of Surgical Therapy. l Interventional radiology ablation is an option for selected patients.
p See Chemotherapy Regimens Used with Radiation Therapy.
bb See NCCN Guidelines for Central Nervous System Cancers.
ee See Systemic Therapy for Advanced or Metastatic Disease.
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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No Yes
Treatment Paradigm for Advanced NSCLC, 2015
1st-line
Advanced Stage IV
Adenocarcinoma
Large cell
NSCLC NOS
Suitable for standard
chemotherapy
EML4-ALK translocation
EGFR
mutation
Non-SqCC
NO or unknown
Non-alimta
Non-avastin
PT-based doublets
No
Yes
Yes
EGFR
TKI
Relapse
2nd
line Suggest Rebiopsy
Alimta
platinum
suggested
±Avastin
Platinum-
based doublet
+/- Avastin
BSC or
single agent
chemotherapy
or EGFR TKI
Maintenance Tx
Relapse
EGFR TKI: Erlotinib, gefitinib, afatinib
Chemotherapy: docetaxel, pemetrexed other single agent ReTx w EGFR TKI for still sensitive mt
1st-line
Yes
Crizotinib
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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NSCLC maintenance therapy(MT)> suggested flow
NSCLC(EGFR-Wild Type)
Histology Non-squamous squamous
1st line Platinum -Pemetrexed Platinum doublet
Disease-control after 1st line
High probability for 2nd
line
Good response Good PS
Low probability for 2nd
line
SD/PR still bulky Low PS
Poor tolerance or
Indolent disease
Good tolerance or
Rapid disease Poor tolerance or
Indolent disease
Good tolerance or
Rapid disease
Close follow up
Continuation MT
Close follow up Switch MT (pemetrexed, erlotinib)
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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SYSTEMIC THERAPY FOR METASTATIC
DISEASE
HISTOLOGIC SUBTYPE
ALK positive
Squamous cell
carcinoma
·Establish histologic
subtype with adequate tissue for molecular
testing (consider rebiopsy if
appropriate)
·Smoking cessation
counseling
·Integrate palliative
careb
·Adenocarcinoma
·Large Cell
·NSCLC not otherwise
specified (NOS)
Metastatic
Disease
·Consider EGFR mutation and ALK
especially in never smokers or small biopsy
specimens, or mixed
histology
Consider ROS1 testing
Consider BRAF testing
·EGFR ± ALK testing
should be conducted as part of multiplex/next-
generation sequencing
PD-L1 testing
Sensitizing EGFR mutation and ALK ,ROS1, BRAF PD-L1negative or unknown
See First-Line
Therapy(Page
18)
See First-Line
Therapy(Page
19)
See First-Line
Therapy(Page
20)
·EGFR mutation testing (category 1)
·ALK testing (category
1)
ROS1 testing
BRAF testing
·EGFR ± ALK testing should be conducted as
part of multiplex/next-
generation sequencing
• PD-L1 testing
See First-Line
Therapy(Page 18)
See First-Line
Therapy(Page 19)
See First-Line
Therapy(Page 21)
Sensitizing EGFR mutation
positive
ALK positive
Both sensitizing EGFR mutation andALK ,
ROS1, BRAF PD-L1are negative or unknown
ROS1 positive
PD-L1 positive and EGFR, ALK, ROS1,BRAF
negative or unknown
ROS1 positive
BRAF V600Epositive
PD-L1 positive and EGFR, ALK, ROS1
BRAF
negative or unknown
BRAF V600Epositive
Sensitizing EGFR mutation
positive
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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AENOCARCINOMA, LARGE CELL, NSCLC NOS: SENSITIZING EGFR MUTATION POSITIVE
FIRST-LINE THERAPY
Sensitizing
EGFR
mutation
positive
EGFR mutation discovered prior to first-line
chemotherapy
Progression
EGFR mutation discovered during first-line
chemotherapy
Gefitinib
Erlotinib or
Afatinib (category 1)
Or
Osimertinib
Interrupt or complete
planned chemotherapy, start
gefitinib, erlotinib or
afatinib or osimertinib May add EGFR TKI to
current
chemotherapy (2B)
Symptomatic
Asymptomatic
Brain
Systemic
Isolated Lesion
Multiple lesions
Consider local therapy Osimertinib and continue gefitinib
Consider WBRT and Osimertinib continue gefitinib, erlotinib or afatinib
Isolated Lesion
Multiple lesions
Consider local therapy and continue gefitinib, erlotinib or afatinib
See First-line therapy options for Adenocarcinoma(Page 20) or Squamous cell carcinoma(Page 21) ± Gefitinib or erlotinib or PD-L1 expression positive (≥50%)
• Consider local
therapy
• Osimertinib
or Continue gefitinib, erlotinib or afatinib
Progression, See First-line therapy options for Adenocarcinoma (Page 20) or Squamous cell carcinoma
(Page 21)
T790M
testing
T790M+
T790M-
Osimertinib
(if not previously
given)
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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ADENOCARCINOMA, LARGE CELL, NSCLC NOS: ALK POSITIVE
ALK
POSITIVE
Alectinib
Preferred
or
Crizotinib
Or
Ceritinib
ALK rearrangement
discovered prior
to first-line chemotherapy
ALK rearrangement
discovered during first-
line chemotherapy
FIRST-LINE THERAPY
Progression
Symptomatic
Asymptomatic
Brain
Systemic
Isolated Lesion
Multiple lesions
Consider local therapy
and continue crizotinib
or • Ceritinib or alectinib Or brigatinib
Consider WBRT and
continue crizotinib
or • Ceritinib or alectinib Or brigatinib Isolated
Lesion
Multiple lesions
Consider local therapy and continue crizotinib
Consider platinum doublet ± bevacizumab Ceritinib or alectinib Or brigatinib
• Consider local therapy Continue crizotinib
or • Ceritinib or alectinib Or brigatinib Symptomatic
systemic progression after local therapies and/ or after switching to ceritinib. See First- line therapy options for Adenocarcinoma (Page 20) or Squamous cell carcinoma (Page 21)
or PD-L1
expression
positive
(≥50%)
Complete planned
chemotherapy,
including
maintenance
therapy, or
interrupt,
followed by
alectinib or
ceritinib
or crizotinib
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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ROS1 REARRANGEMENT POSITIVEa SUBSEQUENT THERAPY
ROS1
rearrangement
positive
Progression
FIRST-LINE THERAPY
Crizotinib
(preferred)
Or
Ceritinib
See First-line therapy options
or
PD-L1 expression positive
(≥50%)
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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BRAF V600E MUTATION POSITIVE
FIRST-LINE THERAPY
SUBSEQUENT THERAPY
BRAF V600E
mutation
positive
Dabrafenib + trametinib
Or
See Initial cytotoxic
therapy options
Progression
See Initial cytotoxic therapy options
Progression
Dabrafenib + trametinib
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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PD-L1 EXPRESSION POSITIVEa
SUBSEQUENT THERAPY
FIRST-LINE THERAPY
See First-line therapy
options for
Adenocarcinoma or
Squamous cell carcinoma
Pembrolizumab
(category 1)
Progression
PD-L1
expression
positive (≥50%)
and EGFR, ALK,
ROS1,BRAF
negative
or unknown
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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ADENOCARCINOMA, LARGE CELL, NSCLC NOS: EGFR MUTATION AND ALK NEGATIVE OR UNKNOWN
Systemic immune checkpoint
inhibitors (preferred)
pembrolizumab (category 1)
or atezolizumab
If not already given:
Docetaxel
or Pemetrexed
or Erlotinib, Gefitinib
or Gemcitabine
or Ramucirumab+docetaxel
or Nivolumab
Best supportive care
or Erlotinib, Gefitinib
Doublet Chemotherapy (category 1) or Bevacizumab + chemotherapy (if criteria met)
qq
Chemotherapy Best supportive care
FIRST-LINE THERAPY
PS 0-1
PS 2
PS 3-4
Continuation maintenance bevacizumab (category 1)
pemetrexed (category 1)
bevacizumab + pemetrexedrr gemcitabine (category 2B) or
Switch maintenance (category 2B)
pemetrexed or erlotinib or
Close observation
Progression
Response or stable disease
Tumor response evaluation
4-6 cycles (total)
Progression
Response or stable disease
Tumor response evaluation
SECOND-LINE THERAPY
PS 0-2
PS 3-4
See Second-line therapy, above
Progression, see Second- line therapy, above
Progression, see Third-line therapy
qq Criteria for treatment with bevacizumab + chemotherapy: non-squamous NSCLC,and no recent history of hemoptysis. Bevacizumab should not be given as a single agent, unless as maintenance if initially used with chemotherapy.
rr If bevacizumab was used with a first-line pemetrexed/platinum chemotherapy regimen.
*Erlotinib has been removed in NCCN guideline 2017 V2
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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Continuation maintenance gemcitabine (category 2B)
or Switch maintenance (category 2B)
erlotinib or docetaxel or Close observation
Tumor response evaluation
Progression
Response or stable disease
SECOND-LINE THERAPY
Progression, see Second- line therapy, above
PS 0-2
PS 3-4
Best supportive care
Doublet chemotherapy
FIRST-LINE THERAPY
PS 3-4
PS 0-1
SQUAMOUS CELL CARCINOMA
Chemotherapy
Progression
Response or stable disease
4-6 cycles (total)
Tumor Response evaluation
Systemic immune checkpoint
inhibitors (preferred)
• Nivolumab (category 1)or
pembrolizumab (category 1)
or atezolizumab
or Other systemic therapy: If not already given: Nivolumab orDocetaxel orErlotinib or Gemcitabine or Ramucirumab+ docetaxel
Progression, see Third line therapy
Best supportive care or Erlotinib
See Second-line therapy, above
PS 2
*Erlotinib has been removed in NCCN guideline 2017 V2
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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ADENOCARCINOMA, LARGE CELL, NSCLC NOS, or SQUAMOUS CELL CARCINOMA : THIRD-LINE THERAPY
THIRD-LINE THERAPY
PS 3-4
Best supportive care or Clinical trial
PS 0-2
PS 3-4
PS 0-2
Progression
Progression
If not already given: Docetaxel or Pemetrexed (nonsquamous) or
Gefitinib
(nonsquamous) Erlotinib or Gemcitabine
Erlotinib
or
Gefitinib
(nonsquamous) or Best supportive care
Best supportive care
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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小細胞肺癌治療指引 Treatment outline for SCLC
INITIAL
DIAGNOSIS
STAGING WORK-UP CLINICAL STAGE INITIAL THERAPY
DIAGNOSIS
IAG
STAGING
CT chest
MRI brain
Bone scan Bone marrow biopsy
LIMITED STAGE
Etoposide+cisplatin
or carboplatin (4-6 cycles)
Concomitant thoracic
irradiation as early as
possible
EXTENSIVE STAGE
Etoposide+cisplatin
or carboplatin (4-6 cycles)
COMPLETE RESPONSE
Prophylactic cranial irradiation
Observe for progression
PARTIAL RESPONSE
Prophylactic cranial
irradiation
Observe for progression
PROGRESSION(Performance Status 0-2)
Topotecan or
Cyclophosphamide/doxorubicin/vincristine
LONG-TERM REMISSION
Surveilance for second
primary cancer
Smoking cessation
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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DIAGNOSIS INITIAL EVALUATIONa STAGE
•H&P
•Pathology review
•CBC with differential, platelets
•Electrolytes, liver function tests
(LFTs), Ca, LDH
•BUN, creatinine
•Chest/liver/adrenal CT with IV contrast whenever possible
•Brain MRIa,b (preferred) or CT with
IV contrast whenever possible
•PET-CT scan (if limited stage is
suspected)a,c
•Smoking cessation counseling
and intervention
Small cell or combined small
cell/non-small cell
lung cancer on
biopsy or cytology of primary or
metastatic site
Limited stage
(See ST-1 for TNM
Classification)
Extensive stage (See ST-1 for TNM
Classification)
See Additional
Workup (SCL-2)
See Initial
Treatment (SCL-4)
aIf extensive stage is established, further staging evaluation is optional. However, brain imaging, MRI (preferred), or CT with IV contrast should be obtained in all patients.
bBrain MRI is more sensitive than CT for identifying brain metastases and is preferred over CT.
cIf PET/CT is not available, bone scan may be used to identify metastases. Pathologic confirmation is recommended for lesions detected by PET/CT that alter stage.
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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STAGE ADDITIONAL WORKUP
Limited stage (See ST-1 for TNM
Classification)
•If pleural effusion is present, thoracentesis is recommended; if
thoracentesis inconclusive,
consider thoracoscopyd
•Pulmonary function tests (PFTs) (if clinically indicated)
•Bone imaging (radiographs or MRI) as appropriate if PET-CT
equivocal
•Unilateral marrow aspiration/biopsy in select
patientse
Clinical stage
T1-2, N0
Limited stage in
excess of T1-T2, N0
Bone marrow biopsy, thoracentesis, or bone studies
consistent with malignancy
PET-CT scanf
(if not previously
obtained)
Pathologic
mediastinal
stagingg,h
See Initial
Treatment (SCL-3)
See Initial
Treatment (SCL-3)
See Extensive-Stage
Disease (SCL-4)
dWhile most pleural effusions in patients with lung cancer are due to tumor, there are a few patients in whom multiple cytopathologic examinations of pleural fluid are negative for tumor and fluid is non-bloody and not an exudate. When these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging element. Pericardial effusion is classified using the same criteria.
eSelection criteria include: nucleated red blood cells (RBCs) on peripheral blood smear, neutropenia, or thrombocytopenia.
fPET-CT scan to identify distant disease and to guide mediastinal evaluation, if not previously done. gSee Principles of Surgical Resection (SCL-A).
hMediastinal staging procedures include mediastinoscopy, mediastinotomy, endobronchial or esophageal ultrasound-guided biopsy, and video-assisted thoracoscopy.
If endoscopic lymph node biopsy is positive, additional mediastinal staging is not required.
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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TESTING RESULTS INITIAL TREATMENTj ADJUVANT TREATMENT
Pathologic mediastinal stagingg,h,i
negative
Clinical stage
T1-2, N0
Limited stage in
excess of T1-2, N0
Pathologic
mediastinal stagingg,h
positive or medically
inoperable or decision made not to pursue
surgical resection
Good PS (0-2)
Poor PS (3-4)
due to SCLC
Poor PS (3-4) not
due to SCLC
Chemotherapyl + concurrent
RTm (category 1)
Chemotherapyl ± RTm
Individualized treatment
including supportive carej
Good performance
status (PS 0-2)
Poor PS (3-4)
due to SCLC
Poor PS (3-4) not
due to SCLC
Lobectomyg,k (preferred) and
mediastinal lymph
node dissection
or sampling N+
N0
Concurrent chemotherapyl+
mediastinal RTm
Chemotherapyl
Chemotherapyl + concurrent
thoracic RTm (category 1)
Chemotherapyl ± RTm
Individualized treatment
including supportive carej
See Response
Assessment +
Adjuvant Treatment
(SCL-5)
See Response
Assessment +
Adjuvant Treatment
(SCL-5)
gSee Principles of Surgical Resection (SCL-A).
hMediastinal staging procedures include mediastinoscopy, mediastinotomy, endobronchial or esophageal ultrasound-guided biopsy, and video-assisted thoracoscopy. If endoscopic lymph node biopsy is positive, additional mediastinal staging is not required.
iPathologic mediastinal staging is not required if the patient is not a candidate for surgical resection or if non-surgical treatment is pursued. jSee Principles of Supportive Care (SCL-B). kSelect patients may be treated with chemotherapy/RT as an alternative to surgical resection.
lSee Principles of Chemotherapy (SCL-C). mSee Principles of Radiation Therapy (SCL-D).
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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STAGE INITIAL TREATMENTj
Extensive stage
without localized
symptomatic sites
or brain
metastases
Extensive stage
(See ST-1 for TNM
Classification)
Extensive stage + localized
symptomatic sites
Extensive stage with
brain metastases
• Good PS (0-2)
• Poor PS (3-4)
due to SCLC
• Poor PS (3-4)
not due to SCLC
• SVC syndrome • Lobar obstruction
• Bone metastases
Spinal cord
compression
Asymptomatic
Symptomatic
Combination chemotherapyl including supportive carej
See NCCN Guidelines for Palliative Care
Individualized therapy including
supportive carej
See NCCN Guidelines for Palliative Care
Chemotherapyl ± RTm to symptomatic sites If high risk of fracture due to osseous
structural impairment, consider
orthopedic stabilization and
palliative external-beam RTm
RTm to symptomatic sites before
chemotherapy unless immediate
systemic therapy is required. See NCCN Guidelines for Central
Nervous System Cancers
May administer chemotherapy first, with
whole-brain RTm after chemotherapyl
Whole-brain RTm before chemotherapy,l
unless immediate systemic therapy is indicated
See Response
Assessment + Adjuvant Treatment
(SCL-5)
jSee Principles of Supportive Care (SCL-B).
lSee Principles of Chemotherapy (SCL-C).
mSee Principles of Radiation Therapy (SCL-D).
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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RESPONSE ASSESSMENT FOLLOWING
INITIAL THERAPY
ADJUVANT TREATMENT SURVEILLANCE
• Chest x-ray (optional)
• Chest/liver/adrenal CT with IV contrast whenever possible
• Brain MRIb (preferred) or CT
with IV contrast whenever
possible, if prophylactic cranial irradiation (PCI) to be
given
• Other imaging studies,
to assess prior sites of involvement, as clinically
indicated
• CBC, platelets • Electrolytes, LFTs, Ca, BUN,
creatinine
Complete response or
Partial response
Stable
Disease
Primary progressive
disease
Limited
stage After recovery from primary
therapy:
• Oncology follow-up visits every
3-4 mo during y 1-2, every 6 mo during y 3-5, then annually
At
bloodwork as clinically indicated • New pulmonary nodule should
initiate workup for potential new
primary
• Smoking cessation intervention • PET/CT is not recommended for
routine follow-up
See Subsequent Therapy/
Palliative Therapy (SCL-6)
For Relapse, see Subsequent
Therapy (SCL-6)
Extensive
stage
PCIm,n,
(category 1)
PCIm,n,
+thoracicRTm,o
bBrain MRI is more sensitive than CT for identifying brain metastases and is preferred over CT. mSee Principles of Radiation Therapy (SCL-D). nNot recommended in patients with poor performance status or impaired neurocognitive function. oSequential radiotherapy to thorax in selected patients with low-bulk metastatic disease and complete response (CR) or near CR after systemic therapy.
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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PROGRESSIVE DISEASE SUBSEQUENT THERAPY/PALLIATIVE THERAPY
Relapse or primary
progressive disease
PS 0-2
PS 3-4
Subsequent chemotherapyl (category
1 for topotecan, see SCL-C) or
Palliative symptom management,
including localized RT to
symptomatic sites
Palliative symptom management, including localized RT to
symptomatic sites
Continue until two cycles
beyond best response or progression of disease
or development of
unacceptable toxicity
• Palliative symptom
management, including localized RT
to symptomatic sites
• Consider subsequent
chemotherapyl if still
PS 0-2
ISee Principles of Chemotherapy (SCL-C).
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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肺癌輔助化學治療 chemotherapy regimen for adjuvant therapy
※Note: Cisplatin 75-80 mg/m2, no less than 60 mg/m2
Published Chemotherapy Regimens Schedule
Cisplatin 75-80 mg/m 2 day 1;
Vinorelbine 25 mg/m 2 iv days 1 + 8 or
oral Vinorelbine 60-80 mg/m 2 days 1 + 8
Every 21 days for 4 cycles a
Other Acceptable Cisplatin- based Regimens (健保不給付) Schedule
Cisplatin 80 mg/m 2 on day 1
Gemcitabine 1000 mg/m 2 on days 1, 8,15
Every 28 days for 4 cycles d
Cisplatin 75 mg/m 2
Docetaxel 66 mg/m2 d1 or 33 mg/m2 d1 , 8
Every 21 days for 4 cycles e
Subsequent chemotherapy:
˙Clinical trial preferred
˙Relapse<2-3mo,PS 0-2:
Topotecan po orIV Temozolomide
Oral etoposide
Paclitaxel
Docetaxel
Irinotecan
Gemcitabine
Ifosfamide
Relapse>2-3 mo up to 6 mo:
Topotecan po orIV (Category 1) Temozolomide
Oral etoposide
Paclitaxel
Docetaxel
Irinotecan
Gemcitabine
Vinorelbine
Cyclophosphamide/doxorubicin/
Vincristine(CAV)
Relapse>6 mo:original regimen
Consider dose reductions versus growth
factors in the poor performance status patient
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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Chemotherapy Regimens for patients with comorbidities
or patients not able to tolerate cisplatin
Schedule
Gemcitabine 1000 mg/m 2 on days 1, 8, 15 Carboplatin AUC 5 on day 1
Every 28 days for 4 cycles f
Paclitaxel 175 mg/m2 on day 1 Carboplatin AUC 6 on day 1
Every 21 days for 4 cycles d
Docetaxel 66 ~ 72 mg/m2 d1 or 33 ~36 mg/m2 d1, 8 Carboplatin AUC 6
Every 21 days for 4 cycles e
REFERENCES a Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-lung cancer. N Engl J Med
2005;352:2589-2597. d Ohe Y, Ohashi Y, Kubota K, et al. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus
gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol 2007;18:317-323. Epub 2006 Nov 1. e Fossella F, Pereira JR, von Pawel J, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus
vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol 2003;21(16):3016-24. Epub 2003 Jul 1.
f Danson S, Middleton MR, O'Byrne KJ, et al. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer 2003;98(3):542-553.
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Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0
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Small cell lung cancer Limited stage
Cisplatin + Etoposide +/- R/T
Cisplatin 60-80 mg/m2 d1
Etoposide 60-80 mg/m2 d1, 2, 3
Q3-4w x 4 cycles
Minoru Takada et al. Phase III Study of Concurrent Versus Sequential Thoracic Radiotherapy in Combination With Cisplatin and Etoposide
for Limited-Stage Small-Cell Lung Cancer: Results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol 2002;14:3054.
Small cell lung cancer Extensive stage
Cisplatin (Carboplatin) + Etoposide
Etoposide 80 mg/m2 d1, 2, 3
Cisplatin 80 mg/m2 d1 or
Carboplatin AUC = 5 d1
Q3-4w x 4 cycles
Okamoto H et al. Randomized phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elder ly or poor-risk
patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer 2007; 97:162. Ihde DC et al. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with
extensive-stage small cell lung cancer. J Clin Oncol 1994; 12:2022.
Topotecan
Topotecan 1.5 mg/m2 d1-5
Q3w
von Pawel J et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 1999;17:658.
Irinotecan
Irinotecan 100 mg/m2 d1
Qw
Masuda N et al. CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol 1992;10:1225.
http://www.ncbi.nlm.nih.gov/pubmed?term=Masuda%20N%5BAuthor%5D&cauthor=true&cauthor_uid=1321891
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化學治療和胸部放射線治療 Concurrent Chemotherapy/RT Regimens* Good PS
〃Paclitaxel 45-50 mg/m 2 weekly over 1 hour
Carboplatin AUC = 2 mg/mL/min over 30 min weekly or cisplatin 25 mg/m2 day 1,8,15,29, 36 and 42 over 1 hour weekly
〃Docetaxel 20 mg/m 2 weekly over 1 hour
Cisplatin 20-25 mg/m2 over 1 hour weekly or Carboplatin AUC = 2 mg/mL/min over 30 min weekly day 1, 8,15, 29, 36 and 42
〃Navelbine 15 mg/m 2 iv D1, D8 Q3wks
Cisplatin 30 mg/m2 iv D1,8 Q3wks
〃Oral Navelbine 30- 40 mg/m 2 D1, D8 Q3wks
Cisplatin 30 mg/m2 iv D1,8 Q3wks
〃Cisplatin 40 mg/m2 on days 1,8,29, and 36; etoposide 40mg/m2 days 1-5, 29-33; concurrent thoracic RTa 64-70 Gy/6-7wks (preferred)*
〃Cisplatin 80 mg/m2 on days 1 and 29; vinblastine 5 mg/m2/weekly x 5; concurrent thoracic RTb 64-70 Gy/6-7wks (preferred)
〃Carboplatin AUC 5 on day 1, pemetrexed 500 mg/m2 on day1 every 21 days for 4 cycles;
〃Cisplatin 75 mg/m2 on days 1, pemetrexed 500 mg/m2 on day1 every 21 days for 3 cycles;
RT Regimens:*once-daily RT,higher doses of 60-70Gy. *on 45Gy(BID) in 3 weeks to 70Gy in 7 weeks
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REFERENCES aAlbain KS, Crowley JJ, Turrisi AT III, et al. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: A Southwest Oncology Group Phase II Study, SWOG 9019. J Clin Oncol 2002;20:3454-3460.
bCurran WJ Jr, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011;103:1452-1460.
cGovindan R, Bogart J, Stinchcombe T, et al. Randomized phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small-cell lung cancer: Cancer and Leukemia Group B trial 30407. J Clin Oncol
2011;29:3120-3125. dVokes EE, Senan S, Treat JA, Iscoe NA. PROCLAIM: A phase III study of pemetrexed, cisplatin, and radiation therapy followed by
consolidation pemetrexed versus etoposide, cisplatin, and radiation therapy followed by consolidation cytotoxic chemotherapy of choice in locally advanced stage III non-small-cell lung cancer of other
than predominantly squamous cell histology. Clin Lung Cancer 2009;10:193-198. *Randomized data supports full dose cisplatin over carboplatin-based regimens. Carboplatin regimens have not been adequately tested. gScagliotti GV, Turrisi III AT: Docetaxel-based combined-modality chemoradiotherapy for locally advanced non-small cell lung cancer
(review). The Oncologist 2003; 8:361-374 hVokes EE, Herndon II JE, Green MR, et al: Randomi zed Phase II Study of Cisplatin With Gemcitabine or Paclitaxel or Vinorelbine as
Induction Chemotherapy Followed by Concomitant Chemoradiotherapy for Stage IIIB Non–Small-Cell Lung Cancer: Cancer and Leukemia Group B Study 9431 J Clin Oncol 2002; 20:4191-4198
iKrzakowski M, Provencio M, Riggi M, et al: Oral Vinorelbine and Cisplatin as Induction Chemotherapy and Concomitant Chemo-Radiotherapy in Stage III Non-small Cell Lung Cancer Final Results of an International Phase II Trial. J Thorac Oncol. 2008;3: 994–1002
Sequential Chemotherapy/RT Regimens
〃Paclitaxel→ 175 mg/m2 every 3 weeks over 3 hours, 2 cycles
Carboplatin AUC 6, 2 cycles or cisplatin 75- 80 mg/m2
〃followed by thoracic RT 60~70 Gy/ 2 Gy per fractions c.d beginning on day 42 d Sterotatic Body Radrosurgery:SBRT, 10~12Gy×4 or
other regimens in clinical trials.
〃Cisplatin 80 mg/m2 on days 1 and 29; vinblastine 5 mg/m2/weekly on days 1, 8, 15, 22,and 29; followed by RTb
REFERENCES
bCurran WJ Jr, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011;103:1452-1460.
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c Belani CP, Choy H, Bonomi P, et al. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol 2005;23(25):5883-5891.
d NCCN 2011,version 2 Concurrent Chemotherapy/RT Followed by Chemotherapy
〃Paclitaxel 45-50 mg/m2 weekly; carboplatin AUC 2, concurrent thoracic RT followed by 2 cycles of paclitaxel 175 mg/m2 and carboplatin
AUCe
〃Cisplatin 40 mg/m2 on days 1,8,29, and 36; etoposide 40 mg/m2 days 1-5, 29-33; concurrent thoracic RT followed by cisplatin 40mg/m2
and etoposide 40 mg/m2 x 2 additional cycles (category 2B)a
*This regimen can be used as neoadjuvant chemoradiotherapy. Cisplatin and etoposide is the preferred regimen. If weekly carboplatin and paclitaxel is used because the patient is not able to tolerate concurrent full-dose cisplatin and radiotherapy, the treating physician should
consider 2 cycles of full-dose platinum therapy after local treatment is completed. eBelani CP, Choy H, Bonomi P, et al. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-
cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005;23:5883-5891.
PCI:Prophylactic Cranial Irradiation
The preferred dose for PCI to the whole brain is 25 Gy in 10 daily fractions .A shorter course (eg, 20Gy in 5 fractions) may be appropriate in Selected patients with extensive-stage disease.
Thermo-Ablation Therapy 溫度燒融治療(TAT)的原則
包括: 射頻燒融治療 Radiofrequency Ablation(RFA) & 微波燒融治療 Microwave Ablation(MWA)
1.溫度燒融治療(TAT)是局部治療的一種選擇;它可提供原發或轉移性肺部腫瘤的局部燒融控制,其治療的併發症與副作用小,
費用相對經濟,可適用於心肺功能不良及老年等不宜手術切除病人之局部控制治療。
2.溫度燒融治療(TAT)中 RFA 的有效燒融病灶大小為 2 公分以下; 腫瘤大小 2-5 公分則以 MWA 為宜。
3.對於早期(stage 1~2)NSCLC, 不適合開刀或是拒絕開刀的, TAT 可做為治療的選項(若適合開刀, 仍以開刀做為第一治療選項)。
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4.對於晚期(stage 3~4)NSCLC, TAT 可做為局部控制的一個手段, 若病情需要, 可合併藥物及電療。
5.對於局部控制, 放射線療法和 TAT 兩者並用也許會有加成效果。
6.對於 NSCLC 復發的病人, TAT 可做為局部控制的一個手段。 對於小於五個的多發性肺部轉移腫瘤, 可以重複多次 TAT 治療。
7.若預期局部控制的效果不好 (如肋膜積水,縱膈腔腫瘤)則不建議使用 TAT 治療。
安寧緩和照護原則 若預期疾病難以治癒時,病人存活期小於 6 個月便適合安寧療護(Pomeranz & Brustman, 2005;Waldrop & Rinfrette, 2009) 。
若藉由症狀、檢驗數據、及確切的腫瘤診斷,證實臨床上該惡性腫瘤已經廣泛侵犯、或進展快速;功能分數(Palliative
Performance Scale)低於 70%;拒絕進一步腫瘤治癒性治療,或者在治療之下仍持續惡化者,即可轉介緩和醫療團隊(彭等,
2006)
参考文獻
1. National Comprehensive Cancer Network (NCCN) Practice Guide-lines in Lung Cancer 2014 v2 版
2. Percutaneous RFA of clinical stage I NSCLC J Thorac Cardiovasc Surg. 2011 ;142:24-30. Thermal Ablation of Lung Tumors Surg
Oncol Clin N Am. 2011
3. Hiraki, Takao ;Gobara, Hideo ;Mimura, Hidefumi ;Matsui, Yusuke ;Toyooka, Percutaneous radiofrequency ablation of clinical stage I non-
small cell lung cancer , July 1, 2011 J Thorac Cardiovasc Surg 142(1),Pages: 24-30.
4.國民健康局民國 97 年癌症登記報告
5. Chemotherapy regimens references
6. Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-lung cancer. N Engl J Med
2005;352:2589-2597.
7. Belani CP, Choy H, Bonomi P, et al. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-
cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol 2005;23(25):5883-5891.
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8.Ohe Y, Ohashi Y, Kubota K, et al. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus
gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol
2007;18:317-323. Epub 2006 Nov 1.
9. Fossella F, Pereira JR, von Pawel J, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus
vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol 2003;21(16):3016-24. Epub
2003 Jul 1.
10.Danson S, Middleton MR, O'Byrne KJ, et al. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or
mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer 2003;98(3):542-553.
11.Scagliotti GV, Turrisi III AT: Docetaxel-based combined-modality chemoradiotherapy for locally advanced non-small cell lung cancer
(review). The Oncologist 2003; 8:361-374
12.Vokes EE, Herndon II JE, Green MR, et al: Randomi zed Phase II Study of Cisplatin With Gemcitabine or Paclitaxel or Vinorelbine as
Induction Chemotherapy Followed by Concomitant Chemoradiotherapy for Stage IIIB Non–Small-Cell Lung Cancer: Cancer and
Leukemia Group B Study 9431 J Clin Oncol 2002; 20:4191-4198
13.A Systematic Review of Radiofrequency Ablation for Lung Tumors Ann Surg Oncol. 2008 P.1765~1774
14.Long-term outcome of image-guided percutaneous RFA of lung metastases an open-labeled prospective trial of 148 patients Ann
Oncol. 2010 P. 2017~2022
15.Lung RFA for the Treatment of Unresectable Recurrent NSCLC After Surgical Intervention Cardiovasc Intervent Radiol. 2011
16.Arriagada R,Le Chevalier T,Riviere A,et al. Patterns of failure after prophylactic cranial irradiation in small-cell lung cancer:analysis
Of 505 randomized patients. Annals of oncology 2002;13:748-754.
17.Auperin A, Arriagada R, Pignon JP, et al.Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission.
Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999;341:476-484.
18.Slotman B,Faivre-Finn C,Kramer G, et al.Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007;357:
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