SandboxAlonso

Stage IV

Is pleural or pericardial effusion present (suggestive of M1a) or are findings suggestive of systemic metastasis (M1b) present?

M1a

M1b: solitary site systemic metastasis

Perform the following tests: Perform thoracentesis and/or pericardiocenteis Perform a thoracoscopy if thoracocentesis is inconclusive

Perform the following tests: Brain MRI Bronchoscopy Mediastinal lymph node biopsy If not previously done, PET scan or CT scan

Is the liquid extracted positive for malignant cells?

Are findings suggestive of adrenal metastasis or brain metastasis?

Yes

No

Adrenal

Brain

Local therapy Ambulatory catheter drainage Pleurodesis Mediastinal window PLUS Therapy for metastatic disease (click here for the treatment of local and systemic metastasis and neoplastic recurrence)

Treat according to tumor stage: I II III

Perform a needle aspiration biopsy for metastasis confirmation

Surgical resection + adjuvant radiation therapy Radiation therapy alone: Sterotactic radio surgery + Whole brain radiation therapy OR Sterotactic radio surgery alone PLUS Pathologic evaluation of surgical piece and lymph nodes

If the lung disease is curable, administer local therapy for the adrenal lesion: Surgical adrenal resection OR Radiation therapy OR Administer therapy for metastatic disease in case of not curable lung lesions (click here for the treatment of local and systemic metastasis and neoplastic recurrence)

What is the TN stage of the lung tumor?

T1-2, No-1 T3, N0

T1-2, N2 T3, N1-2 N3, regardless of the T stage T4 regardless of the N stage

Surgical resection of lung tumor + adjuvant chemotherapy OR Neoadjuvant chemotherapy + surgical resection or stereotactic ablative radiation therapy OR Stereotactic ablative radiation therpay alone

Administer therapy for metastatic disease in case of not curable lung lesions (click here for the treatment of local and systemic metastasis and neoplastic recurrence)

Multiple lung cancers

Is there suspicion of multiple lung cancers?

Yes

No

Perform the following tests: If not previously done, PET scan or CT scan Contrast chest CT Brain MRI

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 tratments: Preferred option: Parenchymal sparing resection Radiation therapy Ablatipn therapy

Click here for the treatment of systemic metastasis

Click here for the follow-up recommendations and treatment of recurrence and metastasis

Follow-up

Controls of history + physical exam and chest CT with or without contrast every 6-12 months (first 2 years), then annual controls

Is there evidence of local or regional recurrence OR systemic metastasis?

Local or regional recurrence

Systemic metastasis

Local or regional recurrence

What is the site of the recurrence?

Bronchial obstruction

Mediastinal lymph node

Superior vena cava obstruction

Severe hemoptisis

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 radiotherapy or external-beam radiation therapy)

Yes

No

Administer systemic therapy

Administer chemotherapy + radiation therapy

Are findings suggestive of disseminated disease present?

Yes

No

Click here for the treatment of metastatic disease

Observation OR systemic therapy

Systemic metastasis

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-beam radiation 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

Metastatic disease

What the specific subtype according to the specific histological characteristics of the tumor?

Adenocarcinoma Large cell carcinoma of the lung Not specified non-small cell lung cancer

Squamous cell carcinoma

Perform specific EGFR and ALK mutation testing: What is the specific mutation?

Is the patient a smoker or former smoker?

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

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.

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

Chemotherapy followed by radiotherapy

The list bellow show the options for chemotherapy followed by radiation therapy based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.

• Cisplatin 100 mg/m² on days 1 and 29 + vinblastin 5 mg/m² per week on days 1, 8, 15, 22 and 29, then followed by radiation therapy.
• Paclitaxel 200 mg/m² administered for 3 hours in the first day + carboplatin AUC 6 administered in 1 hour and then every 21 days to a total of 2 cycles followed by thoracic radiation therapy.

Chemotherapy plus radiotherapy, followed by chemotherapy

The list bellow show the options for concomitant chemotherapy plus radiation therapy followed by chemotherapy based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.

• Cisplatin 50 mg/m² on days 1, 8, 29 and 36 + etoposide 50 mg/m² through day 1 to 5 and then 29 to 33 + thoracic radiation therapy, then followed by cisplatin 50 mg/m² + etoposide 50 mg/m² to a total of 2 cycles.
• Paclitaxel 45 to 50 mg/m² once a week + carboplatin AUC 2 + thoracic radiation therapy, then followed by Paclitaxel 200 mg/m² + carboplatin AUC 6 to a total of 2 cycles.

Radiation therapy regimens

Usual Dosages for Definitive Radiation Therapy

Administer fractions of 2 Gy over a period of 6 to 7.5 weeks to a total dose of 60 to 74 Gy.

Neoadjuvant Radiation Therapy Regimen

Administer fractions of 1.8 to 2 Gy over a period of 5 weeks to a total dose of 45 to 50 Gy.

Adjuvant Radiation Therapy Regimens

• Negative surgical piece margins: Administer fractions of 1.8 to 2 Gy over a period of 5 to 6 weeks to a total dose of 40 to 54 Gy.
• Positive surgical piece margins: Administer fractions of 1.8 to 2 Gy over a period of 6 weeks to a total dose of 54 to 60 Gy.
• Extracapsular nodal extension: Administer fractions of 1.8 to 2 Gy over a period of 6 weeks to a total dose of 60 to 70 Gy.
• Residual tumor: Administer fractions of 2 Gy over a period of 6 to 7 weeks to a total dose of 54 to 60 Gy.

Stereotactic Ablative Radiotherapy Usual Dosage

• Peripheral small tumors: 25 to 34 Gy not fractioned.
• Peripheral tumors and chest wall tumors larger than 1 cm: 45 to 60 Gy administered in 3 fractions.
• Central or peripheral tumors smaller than 5 cm: 48 to 60 Gy administered in 4 fractions.
• Central or peripheral tumors principally chest wall tumors smaller that 1 cm: 50 to 55 Gy administered in 5 fractions.
• Central tumors: 60 to 70 Gy administered in 8 to 10 fractions.

Palliative Radiation Therapy Regimens

Listed bellow are the recommended palliative radiation therapy regimens for patients with non-small cell lung cancer according to the 2014 NCCN Non-Small Cell Lung Cancer guidelines

• Obstructive disease: Administer fractions of 3 Gy over a period of 2 to 3 weeks to a total dose of 30 to 45 Gy.
• Bone metastases associated with soft tissue mass: Administer fractions of 4 to 3 Gy over a period of 1 to 2 weeks to a total dose of 20 to 30 Gy.
• Bone metastases not associated with soft tissue mass: Administer fractions of 8 to 3 Gy over a period of 1 to 14 days to a total dose of 8 to 30 Gy.
• Patients with poor performance status and symptomatic chest disease: Administer fractions of 8.5 Gy over a period of 7 to 14 days to a total dose of 17 Gy.
• Metastatic disease in patients who have a poor performance status: Administer fractions of 8 to 4 Gy over a period of 1 to 7 days to a total dose of 8 to 20 Gy.
• Whole brain radiation therapy regimens for metastases to the brain are the following Adapted from the 2014 NCCN Central Nervous System Cancers guidelines:

• 10 fractions of 3 Gy each to a total of 30 Gy.
• 15 fractions of 2.5 Gy each to a total of 37.5 Gy.
• 5 fractions of 4 Gy each to a total of 20 Gy. Good option for patients with poor performance status.

References

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