chung shan medical university hospital...

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

Chung Shan Medical University Hospital 肺癌診療指引 Clinical Guideline 2018 version12.0

- 1 -

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


- 2 -

FINDINGS FOLLOW-UP

Incidental

finding:

subsolid

nodule(s)

on chest CT

Solitary pure

ground-glass

nodules


- 3 -

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


- 4 -

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 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.


- 5 -

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


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)


- 6 -

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.



- 7 -

CLINICAL

ASSESSMENT

PRETREATMENT

EVALUATION

CLINICAL EVALUATION

Stage IIB

(T3 invasion, N0)

Stage IIIA

(T4, extension, N0-1; T3, N1)


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



- 8 -

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.


Stage IIIA (T4, N0-1)

Unresectable

Definitive concurrent

chemoradiation (category 1)

Durvalumab


- 9 -

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 Stage ⅢB (Page 11)

See Treatment for Metastasis(Page 13)



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



- 10 -

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


- 11 -

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.


- 12 -

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.


- 13 -

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.


- 14 -

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


- 15 -

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).


- 16 -

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)


(Page 17)


(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.


- 17 -

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


- 18 -

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)


- 19 -

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


- 20 -

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)


- 21 -

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


- 22 -

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%)


- 23 -

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


- 24 -

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


- 25 -

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



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


- 26 -

Continuation maintenance gemcitabine (category 2B)

or Switch maintenance (category 2B)

erlotinib or docetaxel or Close observation


Progression


SECOND-LINE THERAPY

Progression, see Second- line therapy, above

PS 0-2

PS 3-4


Doublet chemotherapy

FIRST-LINE THERAPY

PS 3-4

PS 0-1

SQUAMOUS CELL CARCINOMA

Chemotherapy

Progression


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


- 27 -

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



- 28 -

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


- 29 -

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.


- 30 -

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.


- 31 -

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).


- 32 -

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).


- 33 -

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.


- 34 -

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).


- 35 -

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


- 36 -

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.


- 37 -

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


- 38 -

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


- 39 -

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.


- 40 -

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)。


- 41 -

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）

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