Adenocarcinoma of the lung medical therapy metastatic cancer

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shanshan Cen, M.D. [2]

Local or Regional Recurrence

  • The algorithm bellow shows the approach for a local or regional recurrence of a non small cell lung cancers are based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[1]
 
 
 
 
 
 
 
 
What is the site of the recurrence?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bronchial obstruction
 
Mediastinal lymph node
 
Superior vena cava obstruction
 
Severe hemoptysis
 
Resectable tumor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Surgical correction of the obstruction: laser therapy, stent or any other surgical procedure
OR
Radiation therapy (external-beam or brachytherapy)
OR
Photodynamic therapy
 
Has the patient received radiation therapy?
 
Chemotherapy + radiation therapy
OR
External-beam radiation therapy
OR
Superior vena cava stent collocation
 
Surgery
OR
Radiation therapy (external-beam or brachytherapy)
OR
Laser therapy, photodynamic therapy or tumor embolization
 
Tumor resection (preferred option)
OR
Radiation therapy (stereotactic ablative radiation therapy or external-beam radiation therapy)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer systemic therapy (Click here for the treatment of metastatic disease)
 
Administer chemotherapy + radiation therapy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Are findings suggestive of disseminated disease present?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Click here for the treatment of metastatic disease
 
 
 
Observation
OR
Click here for the treatment of metastatic disease
 
 
 
 


Systemic Metastasis

  • The algorithm bellow shows the approach for systemic metastasis of a non small cell lung cancers are based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[1]
 
 
 
 
 
 
 
 
What are the characteristics of the metastasis?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diffuse brain metastasis
 
Bone metastasis
 
Localized symptoms
 
Solitary metastasis
 
Multiple metastasis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
External-beam radiation therapy (palliative)
 
External-beam radiation therapy (palliative) + limb stabilization (prevention of pathological fractures)
Denosumab or biophosphonate therapy should be considered
 
External-beamradiation therapy(palliative)
 
Click here for the treatment of stage IV M1b (solitary site metastasis)
 
Click here for the treatment of metastatic disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Click here for the treatment of metastatic disease
 
 
 
 
 
 
 
 
 

Medical Therapy for Metastatic Non Small Cell Lung Cancer

  • The algorithms for the treatment of metastatic non small cell carcinoma of the lung are based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[1]
 
 
 
 
 
 
 
 
 
What the specific subtype according to the specific histological characteristics of the tumor?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Squamous cell carcinoma
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is the patient a smoker or former smoker?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Perform specific EGFR and ALK mutation testing: What is the specific mutation?
 
 
 
 
 
Perform specific EGFR and ALK mutation testing: Is there a mutation in any of those genes present?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sensitizing EGFR mutation
 
ALK mutation
 
Negative EGFR and ALK
 
Click here for the squamous cell carcinoma specific treatment
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Click here for the sensitizing EGFR mutation specific treatment
 
Click here for the specific therapy for the ALK mutation specific treatment
 
Click here for the treatment of negative sensitizing EGFR and ALK mutation metastatic disease
 
 


Metastatic Adenocarcinoma, Large Cell Carcinoma and Not Specified Non-Small Cell Carcinoma

  • The algorithms for the treatment of metastatic adenocarcinoma, large cell carcinoma and not specified non small cell carcinoma of the lung are based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[1]

Positive Sensitizing EGFR Mutation

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Was the mutation discovered before the initiation of first line therapy?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initiate erlotinib or afatinib
 
 
 
Suspend or complete chemotherapy and initiate erlotinib or afatinib
OR
Add erlotinib or afatinib to chemotherapy regimen
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Did the tumor progress or respond?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor progression
 
 
 
Positive response or stable tumor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Symptomatic disease
 
 
 
 
 
Asymptomatic disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Systemic metastasis
 
 
 
 
 
Brain metastasis
 
Continue treatment
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Multiple metastasis
 
Single metastasis
 
Multiple metastasis
 
Single metastasis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Continue treatment, consider local therapy
 
Continue treatment, consider whole brain radiation therapy
 
Continue treatment, consider local therapy
 
Consider platinum based chemotherapy
with or without
Bevacizumab
AND/OR
Erlotinib
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If findings suggestive of progression of the disease are present, click here for the third line therapy
 
 
 
 
 
 
 


Positive ALK Mutation

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Was the mutation discovered before the initiation of first line therapy?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initiate crizotinib
 
 
 
Suspend or complete chemotherapy and initiate crizotinib
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Did the tumor progress or respond?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor progression
 
 
 
Positive response or stable tumor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Symptomatic disease
 
 
 
 
 
Asymptomatic disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Systemic metastasis
 
 
 
 
 
Brain metastasis
 
Continue treatment or change to certinib according to the degree of disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Multiple metastasis
 
Single metastasis
 
Multiple metastasis
 
Single metastasis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Continue treatment, consider local therapy
 
Continue treatment, consider whole brain radiation therapy
 
Continue treatment, consider local therapy
 
Initiate certinib
OR
Consider platinum based chemotherapy
with or without
Bevacizumab
AND/OR
Erlotinib
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If findings suggestive of progression of the disease are present, click here for the third line therapy
 
 
 
 
 
 
 


Negative EGRF and ALK or Unknown Mutation

 
 
 
 
 
 
 
 
What is the performance status (PS) of the patient?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0-1
 
2
 
3-4
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Doublet chemotherapy
OR
Bevacizumab + Chemotherapy
OR
Cetuximab/vinorelbine/cisplatin
 
Chemotherapy
 
Supportive care
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
What was the tumor response to the treatment?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Progression
 
 
 
 
 
Positive response or stable tumor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer 4-6 cycles and assess progression of the disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PS 0-2
 
PS 3-4
 
Tumor progression
 
 
Positive response or stable tumor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initiate docetaxel or pemetrexed or erlotinib or gemcitabine
 
Provide supportive care
 
Initiate docetaxel or pemetrexed or erlotinib or gemcitabine
 
 
Continuation maintenance (cetuximab or gemcitabine)
OR
Switch maintenance (erlotinib or decetaxel)
OR
Close observation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initiate docetaxel or pemetrexed or erlotinib or gemcitabine
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If findings suggestive of progression of the disease are present, click here for the third line therapy
 
 
 
 
 
 
 
 


Metastatic squamous cell carcinoma

  • The algorithm for the treatment of metastatic squamous cell carcinoma are based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[1]
 
 
 
 
 
 
 
 
What is the performance status (PS) of the patient?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0-1
 
2
 
3-4
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cisplatin based chemotherapy
OR
Cetuximab/vinorelbine/cisplatin
 
Chemotherapy
 
Suportive care
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
What was the tumor response to the treatment?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Progression
 
 
 
 
 
Positive response or stable tumor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer 4-6 cycles and assess progression of the disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PS 0-2
 
PS 3-4
 
Tumor progression
 
 
Positive response or stable tumor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initiate docetaxel or erlotinib or gemcitabine
 
Provide suportive care
 
Initiate docetaxel or erlotinib or gemcitabine
 
 
Continue treatment(cetuximab or gemcitabine)
OR
Switch mantainance (erlotinib or docetaxel)
OR
Close observation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initiate docetaxel or pemetrexed or erlotinib or gemcitabine
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If findings suggestive of progression of the disease are present, click here for the third line therapy
 
 
 
 
 
 
 
 


Third line therapy

  • The algorithm below shows the third line therapy for metastatic disease according to the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[1]
 
 
 
 
 
What is the performance status of the patient?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PS 0-2
 
 
 
PS 3-4
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If not previously used, administer any of the following:
  • Docetaxel
  • Erlotinib
  • Gemcitabine
  • Pemetrexed
 
 
 
Administer erlotinib or provide suportive care
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
What is the performance status of the patients after the treatment?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PS 0-2 (stable tumor)
 
PS 3-4 (tumor progression)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Provide supportive care or try experimental treatments
 
Provide supportive care
 
 
 
 


Multiple Lung Cancers

The algorithm for the treatment of multiple non small cell lung cancers are based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[2]

 
 
 
 
 
 
 
 
Is there suspicion of multiple lung cancers?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Perform the following tests:
 
Administer treatment according to the TNM stage of the tumor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is the disease is confined to the chest or is there systemic proliferation?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Disease confined to the chest
 
Systemic proliferation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assess the mediastinal lymph nodes in order to determine the N stage of the tumor
 
Click here for the treatment of systemic metastasis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
What is the N stage of the tumor?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N0-1
 
N2-3
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is the patient symptomatic?
 
Click here for the treatment of systemic metastasis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is the lesion a solitary nodule or are there multiple nodules?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Solitary nodule
 
Multiple nodules
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
What is the risk of turning into a symptomatic disease?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
High
 
Low
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is definitive local therapy possible?
 
 
 
Observation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Consider palliative chemotherapy with or without local Radiation therapy
 
Administer one of the following treatments:
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Click here for the treatment of systemic metastasis
 
 
 
Go to the appropriate algorithm according to the characteristics of the disease: local or regional recurrence or metastasis
 
 
 



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