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(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN1

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines

)

Small Cell Lung Cancer

Version 3.2021 — March 23, 2021

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*Apar Kishor P. Ganti, MD, Chair †

Fred & Pamela Buffett Cancer Center

*Billy W. Loo, Jr., MD, PhD/Vice Chair §

Stanford Cancer Institute

Michael Bassetti, MD §

University of Wisconsin Carbone Cancer Center

Abigail Berman, MD, MSCE §

Abramson Cancer Center

at the University of Pennsylvania

Collin Blakely, MD †

UCSF Helen Diller Family

Comprehensive Cancer Center

Anne Chiang, MD, PhD †

Yale Cancer Center/Smilow Cancer Hospital

Thomas A. D'Amico, MD ¶

Duke Cancer Institute

Afshin Dowlati, MD †

Case Comprehensive Cancer Center/University

Hospitals Seidman Cancer Center and Cleveland

Clinic Taussig Cancer Institute

Robert J. Downey, MD ¶

Memorial Sloan Kettering Cancer Center

Martin Edelman, MD †

Fox Chase Cancer Center

Charles Florsheim

Patient Advocate

Kathryn A. Gold, MD †

UC San Diego Moores Cancer Center

Jonathan W. Goldman, MD † ‡ Þ

UCLA Jonsson Comprehensive Cancer Center

John C. Grecula, MD §

The Ohio State University Comprehensive

Cancer Center - James Cancer Hospital

and Solove Research Institute

Christine Hann, MD †

The Sidney Kimmel Comprehensive

Cancer Center at Johns Hopkins

Wade Iams, MD †

Vanderbilt-Ingram Cancer Center

Puneeth Iyengar, MD, PhD §

UT Southwestern

Simmons Comprehensive Cancer Center

Maya Khalil, MD †

O'Neal Comprehensive Cancer Center at UAB

Marianna Koczywas, MD † ‡ Þ

City of Hope

National Medical Center

Robert E. Merritt, MD ¶

The Ohio State University Comprehensive

Cancer Center - James Cancer Hospital

and Solove Research Institute

Nisha Mohindra, MD †

Robert H. Lurie Comprehensive

Cancer Center of Northwestern University

Julian Molina, MD, PhD ‡ Þ

Mayo Clinic Cancer Center

Cesar Moran, MD ≠

The University of Texas

MD Anderson Cancer Center

Saraswati Pokharel, MD ≠

Roswell Park Comprehensive Cancer Center

Sonam Puri, MD † ‡ Þ

Huntsman Cancer Institute

at the University of Utah

Angel Qin, MD †

University of Michigan Rogel Cancer Center

Chad Rusthoven, MD §

University of Colorado Cancer Center

Jacob Sands, MD †

Dana Farber/Brigham and Women's

Cancer Center

Rafael Santana-Davila, MD †

Fred Hutchinson Cancer Research Center/

Seattle Cancer Care Alliance

Michael Shafique, MD †

Moffitt Cancer Center

Saiama N. Waqar, MBBS, MSCI †

Siteman Cancer Center at Barnes-

Jewish Hospital and Washington

University School of Medicine

NCCN

Miranda Hughes, PhD

Jennifer Keller, MSS

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NCCN Guidelines Panel Disclosures

‡ Hematology/Hematology oncology

Þ Internal medicine

† Medical oncology

≠ Pathology

§ Radiotherapy/Radiation oncology

¶ Surgery/Surgical oncology

*Discussion writing committee member

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

NCCN Guidelines Index

Table of Contents

Discussion

Clinical Trials: NCCN believes that

the best management for any patient

with cancer is in a clinical trial.

Participation in clinical trials is

especially encouraged.

To nd clinical trials online at NCCN

Member Institutions, click here:

nccn.org/clinical_trials/member_

institutions.aspx.

NCCN Categories of Evidence and

Consensus: All recommendations

are category 2A unless otherwise

indicated.

See NCCN Categories of Evidence

and Consensus.

NCCN Categories of Preference:

All recommendations are considered

appropriate.

See NCCN Categories of Preference.

NCCN Small Cell Lung Cancer Panel Members

Summary of the Guidelines Updates

Initial Evaluation and Staging (SCL-1)

Limited Stage, Workup and Treatment (SCL-2)

Extensive Stage, Initial Treatment (SCL-5)

Response Assessment Following Initial Therapy and Surveillance (SCL-6)

Progressive Disease: Subsequent Therapy and Palliative Therapy (SCL-7)

Signs and Symptoms of Small Cell Lung Cancer (SCL-A)

Principles of Pathologic Review (SCL-B)

Principles of Surgical Resection (SCL-C)

Principles of Supportive Care (SCL-D)

Principles of Systemic Therapy (SCL-E)

Principles of Radiation Therapy (SCL-F)

Staging (ST-1)

Lung Neuroendocrine Tumors – See the NCCN Guidelines for Neuroendocrine and Adrenal

Tumors

The NCCN Guidelines

are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment.

Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical

circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network

(NCCN

) makes no representations or

warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN

Guidelines are copyrighted by National Comprehensive Cancer Network

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

NCCN Guidelines Index

Table of Contents

Discussion

UPDATES

Updates in Version 1.2021 of the NCCN Guidelines for Small Cell Lung Cancer from Version 4.2020 include:

SCL-5

• Term revised: whole-brain RT (WBRT)

brain RT. Also for SCL-E 3 of

• Initial Treatment revised for Extensive stage with brain metastases,

Asymptomatic: May administer systemic therapy rst, with whole-

brain RT (WBRT) before brain RT after completion of induction

systemic therapy

• Footnote r revised: For patients with asymptomatic brain

metastases receiving systemic therapy before WBRT Brain MRI

(preferred) or CT with contrast should be repeated after every 2

cycles of systemic therapy until brain RT is initiated or systemic

therapy is completed, whichever is rst and at completion of

therapy (see SCL-6). If brain metastases progress while on systemic

therapy, then initiate WBRT

brain RT should be initiated before

completion of systemic therapy. See Principles of Radiation Therapy

(SCL-F).

SCL-6

• Footnote removed: See Principles of Surgical Resection (SCL-C).

SCL-B 1 of 2

• Pathologic Evaluation, bullet 6 added: SCLC is often associated

with necrosis. However, necrosis, usually punctate, is also seen

in atypical carcinoid tumors. Counting mitotic gures helps to

distinguish these two entities.

SCL-C

• Bullet 3 added: Surgery may be considered for selected patients with

T3 (based on size), N0 SCLC, if invasive mediastinal lymph node

staging is negative.

• Bullet 5 revised: The benet of PCI is unknown in patients who

have undergone complete resection for pathologic stage I–IIA (T1–

2,N0,M0) SCLC; consider PCI or brain MRI surveillance for N0. These

patients...

SCL-E 1 of 5

• Primary or Adjuvant Therapy for Limited Stage SCLC, dosing

statement revised: Maximum of 4–6 cycles

Four cycles of systemic

therapy are recommended.

• Heading revised: Primary or Adjuvant

Therapy for Extensive Stage

SLCL

Dosing statement revised: Maximum of 4–6 cycles

Four cycles of

therapy are recommended, but some patients may receive up to 6

cycles based on response and tolerability after 4 cycles.

• Footnote removed: Regimen not recommended for relapsed disease

in patients on maintenance atezolizumab or durvalumab at time of

relapse. For patients who relapse after >6 months of atezolizumab

or durvalumab maintenance therapy, recommend re-treatment with

carboplatin + etoposide alone or cisplatin + etoposide alone.

Continued

Updates in Version 2.2021 of the NCCN Guidelines for Small Cell Lung Cancer from Version 1.2021 include:

SCL-E 2 of 5

• Nivolumab was moved from a category 2A to a category 3 recommendation.

Updates in Version 3.2021 of the NCCN Guidelines for Small Cell Lung Cancer from Version 2.2021 include:

SCL-D

• Bullet 3 added: Trilaciclib may be used as a prophylactic option to decrease the incidence of chemotherapy-induced myelosuppression

when administered before (or G-CSF may be administered after) platinum/etoposide ± immune checkpoint inhibitor-containing regimens or a

topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC).

SCL-E 2 of 5

• Pembrolizumab was revised from a category 2A to a category 3 recommendation.

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

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Discussion

SCL-E 2 of 5

• Other Recommended Regimens, regimen revised: Nivolumab ± ipilimumab

• Footnote b revised: Regimen not recommended for relapsed disease in patients on maintenance atezolizumab or durvalumab at time of

relapse. For patients who relapse after >6 months of atezolizumab or durvalumab maintenance therapy, recommend re-treatment with

carboplatin + etoposide alone or cisplatin + etoposide alone.

SCL-E 3 of 5

• Response Assessment, bullet 2 added: Response assessment after adjuvant therapy involves chest/abdomen/pelvic CT with contrast and

brain MRI (preferred) with contrast or brain CT with contrast (see SCL-6).

SCL-E 4 of 5

• Reference 18 revised: Hellmann MD, Ott PA, Zugazagoitia J, et al. Nivolumab (nivo) ± ipilimumab (ipi) in advanced small-cell lung cancer

(SCLC): First report of a randomized expansion cohort from CheckMate 032 [abstract]. J Clin Oncol 2017;35: Abstract 8503. Ready NE,

Ott PA, Hellmann MD, et al. Nivolumab monotherapy and nivolumab plus ipilimumab in recurrent small cell lung cancer: results from the

CheckMate 032 randomized cohort. J Thorac Oncol 2020;15:426-435.

• Reference 19 added: Chung HC, Lopez-Martin JA, Kao S, et al. Phase 2 study of pembrolizumab in advanced small-cell lung cancer (SCLC):

KEYNOTE-158. J Clin Oncol 2018;36: Abstract 8506.

SCL-F 2 of 5

• Extensive stage, sub-bullet 3 added: Based on two randomized trials, immunotherapy during and after chemotherapy is a rst-line approach,

but these studies did not include consolidative thoracic RT. Nevertheless, consolidative thoracic RT after chemoimmunotherapy can be

considered for selected patients as above, during or before maintenance immunotherapy (there are no data on optimal sequencing or

safety).

SCL-F 3 of 5

• Prophylactic Cranial Irradiation (cont.)

Bullet 5 added: Consider hippocampal-sparing PCI using IMRT.

Bullet 6 added: Current randomized trials are evaluating whether MRI surveillance alone is non-inferior to MRI surveillance plus PCI on

overall survival and whether hippocampal-sparing PCI reduces memory impairment compared to whole brain PCI in LS-SCLC and ES-

SCLC.

• Brain Metastases, bullet 1 revised by adding: A current trial is comparing SRS to hippocampal-sparing WBRT plus memantine in this setting.

UPDATES

Updates in Version 1.2021 of the NCCN Guidelines for Small Cell Lung Cancer from Version 4.2020 include:

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

SCL-1

• H&P

• Pathology review

• CBC

• Electrolytes, liver function tests

(LFTs), BUN, creatinine

• Chest/abdomen/pelvis CT with

contrast

• Brain MRI

a,d

(preferred) or CT with

contrast

• Consider PET/CT scan (skull base

to mid-thigh), if limited stage is

suspected or if needed to clarify

stage

a,e,f

• Smoking cessation counseling

and intervention. See the NCCN

Guidelines for Smoking Cessation.

• Molecular proling (only for never

smokers with extensive stage)

If extensive stage is established, further staging evaluation is optional. However, brain imaging MRI (preferred), or CT with contrast should be obtained in all patients.

See Signs and Symptoms of Small Cell Lung Cancer (SCL-A).

See Principles of Pathologic Review (SCL-B).

Brain MRI is more sensitive than CT for identifying brain metastases and is preferred over CT.

If 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.

Molecular profiling may be considered in never smokers with extensive-stage SCLC to help clarify diagnosis and evaluate for potential targeted treatment options.

DIAGNOSIS INITIAL EVALUATION

STAGE

Small cell lung

cancer (SCLC) or

combined SCLC/

non-small cell lung

cancer (NSCLC) on

biopsy or cytology

of primary or

metastatic site

Limited stage

(See ST-1 for TNM

Classication)

Extensive stage

(See ST-1 for TNM

Classication)

See Additional

Workup (SCL-2)

See Initial

Treatment (SCL-5)

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

Limited stage

(See ST-1 for TNM

Classication)

SCL-2

While 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.

Selection criteria include: nucleated red blood cells (RBCs) on peripheral blood smear, neutropenia, or thrombocytopenia suggestive of bone marrow infiltration.

See Principles of Surgical Resection (SCL-C).

Mediastinal 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.

Pathologic mediastinal staging is not required if the patient is not a candidate for surgical resection or if non-surgical treatment is pursued.

STAGE ADDITIONAL WORKUP

• If pleural eusion is present,

thoracentesis is

recommended; if

thoracentesis inconclusive,

consider thoracoscopy

• Pulmonary function tests

(PFTs) during evaluation

for surgery or denitive

radiation therapy (RT)

• Bone imaging (radiographs

or MRI) as appropriate if

PET/CT equivocal (consider

biopsy if bone imaging is

equivocal)

• Unilateral marrow

aspiration/biopsy in select

patients

Clinical stage

I–IIA (T1–2,N0,M0)

Limited stage

IIB–IIIC (T3–4,N0,M0;

T1–4,N1–3,M0)

Bone marrow biopsy,

thoracentesis, or bone studies

consistent with malignancy

Pathologic mediastinal

staging

i,j,k

See Initial

Treatment (SCL-3)

See Initial

Treatment (SCL-4)

See

Extensive-Stage

Disease (SCL-5)

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

SCL-3

TESTING RESULTS

INITIAL TREATMENT ADJUVANT TREATMENT

See Principles of Surgical Resection (SCL-C).

Mediastinal 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.

Pathologic mediastinal staging is not required if the patient is not a candidate for surgical resection or if non-surgical treatment is pursued.

Select patients may be treated with systemic therapy/RT as an alternative to surgical resection.

See Principles of Systemic Therapy (SCL-E).

See Principles of Radiation Therapy (SCL-F).

For patients receiving adjuvant systemic therapy ± RT, response assessment should occur only after completion of adjuvant therapy (SCL-6); do not repeat scans to

assess response during adjuvant treatment.

For patients receiving systemic therapy + concurrent RT, response assessment should occur only after completion of initial therapy (SCL-6); do not repeat scans to

assess response during initial treatment. For patients receiving systemic therapy alone or sequential systemic therapy followed by RT, response assessment by chest/

abdomen/pelvis CT with contrast should occur after every 2 cycles of systemic therapy and at completion of therapy (SCL-6).

Clinical stage

I–IIA (T1–2,N0,M0)

Pathologic mediastinal

staging

i,j

negative

Pathologic

mediastinal staging

i,j

positive

Lobectomy

i,l

(preferred) and

mediastinal lymph

node dissection or

sampling

N0 Systemic therapy

See Response

Assessment +

Adjuvant Treatment

(SCL-6)

Systemic therapy

± mediastinal RT

(sequential or

concurrent)

Medically inoperable or

decision made not to

pursue surgical resection

See SCL-4

Systemic therapy

+ concurrent RT

(See SCL-4)

Systemic therapy

+ mediastinal RT

(sequential or

concurrent)

See Response

Assessment +

Adjuvant Treatment

(SCL-6)

SABR

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

SCL-4

INITIAL TREATMENT

See Principles of Systemic Therapy (SCL-E).

See Principles of Radiation Therapy (SCL-F).

For patients receiving systemic therapy + concurrent RT, response assessment should occur only after completion of initial therapy (SCL-6); do not repeat scans to

assess response during initial treatment. For patients receiving systemic therapy alone or sequential systemic therapy followed by RT, response assessment by chest/

abdomen/pelvis CT with contrast should occur after every 2 cycles of systemic therapy and at completion of therapy (SCL-6).

See Principles of Supportive Care (SCL-D).

Good PS (0–2)

Poor PS (3–4)

due to SCLC

Poor PS (3–4)

not due to SCLC

Systemic therapy

concurrent RT

(category 1)

Systemic therapy

± RT

(concurrent or sequential)

See Response

Assessment +

Adjuvant Treatment

(SCL-6)

Limited stage

IIB–IIlC (T3–4,N0,M0;

T1–4,N1–3,M0)

Individualized treatment

including supportive care

See NCCN Guidelines for

Palliative Care

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

Extensive stage

(See ST-1 for TNM

Classication)

SCL-5

See Principles of Systemic Therapy (SCL-E).

See Principles of Radiation Therapy (SCL-F).

See Principles of Supportive Care (SCL-D).

Brain MRI (preferred) or CT with contrast should be repeated after every 2 cycles of systemic therapy until brain RT is initiated or systemic therapy is completed,

whichever is first (see SCL-6). If brain metastases progress while on systemic therapy, brain RT should be initiated before completion of systemic therapy.

See

Principles of Radiation Therapy (SCL-F).

During systemic therapy, response assessment by chest/abdomen/pelvis CT with contrast should occur after every 2–3 cycles of systemic therapy and at completion of

therapy (SCL-6).

STAGE INITIAL TREATMENT

Extensive stage

without localized

symptomatic sites

or brain metastases

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

Combination systemic therapy

including

supportive care

See NCCN Guidelines for Palliative Care

Individualized therapy including

supportive care

See NCCN Guidelines for Palliative Care

• Superior vena

cava (SVC)

syndrome

• Lobar obstruction

• Bone metastases

Spinal cord

compression

Systemic therapy

± RT

symptomatic sites

If high risk of fracture due to osseous

structural impairment, consider

orthopedic stabilization and

palliative external beam RT (EBRT)

to symptomatic sites before

systemic therapy unless immediate

systemic therapy is required.

See NCCN Guidelines for Central

Nervous System Cancers

Asymptomatic

Symptomatic

May administer systemic therapy before

brain RT

after completion of induction

systemic therapy

m,r

Brain RT

before systemic therapy,

unless immediate systemic therapy is

indicated

See Response

Assessment +

Adjuvant Treatment

(SCL-6)

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

SCL-6

RESPONSE ASSESSMENT FOLLOWING

INITIAL THERAPY

ADJUVANT

TREATMENT

SURVEILLANCE

See Signs and Symptoms of Small Cell Lung Cancer (SCL-A).

Brain MRI is more sensitive than CT for identifying brain metastases and is preferred over CT.

See Principles of Radiation Therapy (SCL-F).

See NCCN Guidelines for Survivorship.

Not recommended in patients with poor performance status or impaired neurocognitive function. Increased cognitive decline after PCI has been observed in older

adults (≥60 years) in prospective trials; the risks and benefits of PCI versus close surveillance should be carefully discussed with these patients.

The benefit of PCI is unknown in patients who have undergone complete resection for pathologic stage I–IIA (T1–2,N0,M0) SCLC. See Principles of Surgical

Resection (SCL-C).

Sequential RT to thorax in selected patients, especially with residual thoracic disease and low-bulk extrathoracic metastatic disease that has responded to

systemic therapy.

• Chest/

abdomen/

pelvis CT

with contrast

• Brain MRI

(preferred)

or CT with

contrast

• CBC

• Electrolytes,

LFTs, BUN,

creatinine

Complete

response

or partial

response

Limited

stage

Primary progressive disease

Limited

stage

After completion of initial

therapy:

• Oncology follow-up

visits every 3 mo during

y 1–2, every 6 mo during

y 3, then annually

After completion of initial

or subsequent therapy:

• Oncology follow-up

visits every 2 mo during

y 1, every 3–4 mo during

y 2–3, then every 6 mo

during years 4–5, then

annually

For

Relapse,

see

Subsequent

Therapy

(SCL-7)

See Subsequent Therapy/Palliative Therapy (SCL-7)

Extensive

stage

Prophylactic

cranial irradiation

(PCI)

n,u,v

(category 1)

• Consider PCI

n,u

or MRI brain

surveillance

• Consider

thoracic RT

n,w

Stable

disease

• Provide survivorship

care plan after

completion of initial

therapy

• At every visit: H&P,

chest/abdomen/pelvis;

blood work only as

clinically indicated

• MRI (preferred) or CT

brain with contrast every

3–4 months during y 1,

then every 6 months

during y 2 (regardless of

PCI status)

• New pulmonary nodule

should initiate workup

for potential new

primary

• Smoking cessation

intervention, see the

NCCN Guidelines for

Smoking Cessation

• PET/CT is not

recommended for

routine follow-up

After completion of initial therapy:

• Oncology follow-up visits every 3 mo during y

1–2, every 6 mo during y 3, then annually

After completion of initial or subsequent therapy:

• Oncology follow-up visits every 2 mo during y

1, every 3–4 mo during y 2–3, then every 6 mo

during years 4–5, then annually

Extensive

stage

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

SCL-7

See Principles of Systemic Therapy (SCL-E).

See Principles of Radiation Therapy (SCL-F).

See Principles of Supportive Care (SCL-D).

See NCCN Guidelines for Palliative Care.

Response assessment by chest/abdomen/pelvis CT with contrast should occur after every 2–3 cycles of systemic therapy.

PROGRESSIVE DISEASE SUBSEQUENT THERAPY/PALLIATIVE THERAPY

Relapse

or primary

progressive

disease

PS 0–2

PS 3–4

Subsequent

systemic therapy

m,y

Palliative symptom

management

q,x

including localized

to symptomatic

sites

Palliative symptom

management,

q,x

including

localized RT

to symptomatic sites

Continue until

progression

Development of

unacceptable

toxicity

Response

response or

unacceptable

toxicity

PS 0–2

PS 3–4

Palliative

symptom

management,

q,x

including

localized RT

symptomatic sites

• Consider

subsequent

systemic

therapy

m,y

• Palliative

symptom

management,

q,x

including

localized RT

to symptomatic

sites

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

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Discussion

SIGNS AND SYMPTOMS OF SMALL CELL LUNG CANCER

SCL-A

1 OF 2

Signs and Symptoms Due to Local Primary Tumor Growth

• Cough – endobronchial irritation, bronchial compression

• Hemoptysis – usually central or cavitary lesion

• Wheezing – partially obstructing endobronchial lesion

• Fever – postoperative pneumonia

• Dyspnea – bronchial obstruction, pneumonia, pleural eusion

Signs and Symptoms Due to Primary Tumor Invasion or Regional Lymphatic Metastases

• Hoarseness – left vocal cord paralysis due to tumor invasion or lymphadenopathy in the aortopulmonary window

• Hemidiaphragm elevation – due to phrenic nerve compression

• Dysphagia – due to esophageal compression

• Chest pain – involvement of pleura or chest wall, often dull and non-localized

• SVC syndrome – due to local invasion into mediastinum or lymphadenopathy in right paratracheal region

• Pericardial eusion and tamponade

• Cervical or supraclavicular lymph node enlargement

Signs and Symptoms Due to Extrathoracic (Hematogenous) Metastases

• Brain metastases:

Headache, focal weakness or numbness, confusion, slurred speech, gait instability, incoordination

• Leptomeningeal carcinomatosis:

Headache, confusion, cranial nerve palsy, diplopia, slurred speech, radicular back pain, spinal cord compression

• Adrenal metastases:

Mid-back or ank pain, costovertebral angle tenderness

Adrenal insuciency due to tumor involvement is rare

• Liver metastases:

Right upper quadrant pain or tenderness, jaundice, fatigue, fever, hepatomegaly

• Bone metastases:

Bone pain

Spinal cord compression – back pain, muscle weakness, numbness, paresthesia, loss of bowel and bladder control

• Constitutional:

Anorexia/cachexia – weight loss

Fatigue

Continued

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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Discussion

SIGNS AND SYMPTOMS OF SMALL CELL LUNG CANCER

SCL-A

2 OF 2

Signs and Symptoms of Paraneoplastic Syndromes

• Presence does not imply metastases or incurability

• Endocrine:

Due to ectopic peptide hormone production

Usually reversible with successful anti-tumor therapy

Syndrome of inappropriate antidiuretic hormone secretion (SIADH):

◊ Ectopic vasopressin (antidiuretic hormone, ADH) secretion

◊ Clinically signicant hyponatremia in 5%–10% of SCLC

◊ Malaise, weakness, confusion, obtundation, volume depletion, nausea

◊ Hyponatremia, euvolemia, low serum osmolality, inappropriately concentrated urine osmolality, normal thyroid and adrenal function

Cushing’s syndrome:

◊ Ectopic adrenocorticotropic hormone (ACTH) secretion

◊ Weight gain, moon facies, hypertension, hyperglycemia, generalized weakness

◊ High serum cortisol and ACTH, hypernatremia, hypokalemia, alkalosis

• Neurologic: All specic syndromes are rare

If paraneoplastic neurologic syndrome is suspected, consider obtaining comprehensive paraneoplastic antibody panel

Subacute cerebellar degeneration (anti-Yo antibody) – ataxia, dysarthria

Encephalomyelitis (ANNA-1 [anti-Hu] antibody) – confusion, obtundation, dementia

Sensory neuropathy (anti-dorsal root ganglion antibody) – pain, sensory loss

Eaton-Lambert syndrome (anti-voltage-gated calcium channel antibody) – weakness, autonomic dysfunction

Cancer-associated retinopathy (anti-recoverin antibody) – visual loss, photosensitivity

• Hematologic:

Anemia of chronic disease

Leukemoid reaction – leukocytosis

Trousseau’s syndrome – migratory thrombophlebitis

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Small Cell Lung Cancer

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and this illustration may not be reproduced in any form without the express written permission of NCCN.

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SCL-B

1 OF 2

PRINCIPLES OF PATHOLOGIC REVIEW

Pathologic Evaluation

• Pathologic evaluation is performed to determine the histologic classication of lung tumors and relevant staging parameters.

• The World Health Organization (WHO) tumor classication system provides the foundation for the classication of lung tumors, including

histologic subtype, staging factors, clinical features, molecular characteristics, genetics, and epidemiology.

1-3

• SCLC is a poorly dierentiated neuroendocrine carcinoma. Distinguishing SCLC from other neuroendocrine tumors, particularly typical and

atypical carcinoids, is important due to signicant dierences in epidemiology, genetics, treatment, and prognosis.

4-6

• SCLC can be diagnosed on good-quality histologic samples via high-quality hematoxylin and eosin (H&E)-stained sections or on well-

preserved cytologic samples.

SCLC is characterized by small blue cells with scant cytoplasm, high nuclear-to-cytoplasmic ratio, granular chromatin, and absent or

inconspicuous nucleoli.

SCLC cells are round, oval, or spindle-shaped with molding and high mitotic counts.

7-9

The most useful characteristics for distinguishing SCLC from large-cell neuroendocrine carcinoma (LCNEC) are the high nuclear-to-

cytoplasmic ratio and paucity of nucleoli in SCLC.

• Careful counting of mitoses is essential, because it is the most important histologic criterion for distinguishing SCLC from typical and

atypical carcinoids.

SCLC (>10 mitoses/2 mm

eld); atypical carcinoid (2–10 mitoses/2 mm

eld); typical carcinoid (0–1 mitoses/2 mm

eld)

Mitoses should be counted in the areas of highest activity and per 2 mm

eld, rather than per 10 high-power elds.

In tumors that are near the dened cutos of 2 or 10 mitoses per 2 mm

, at least three 2-mm

elds should be counted and the calculated

mean (rather than the single highest mitotic count) should be used to determine the overall mitotic rate.

1,2

• SCLC is often associated with necrosis. However, necrosis, usually punctate, is also seen in atypical carcinoid tumors. Counting mitotic

gures helps to distinguish these two entities.

• Combined SCLC consists of both SCLC histology and NSCLC histology (squamous cell, adenocarcinoma, spindle/pleomorphic, and/or large

cell). There is no minimal percentage of NSCLC histologic elements required; when any are present along with SCLC, this can be called

combined SCLC.

Immunohistochemical Staining

• Immunohistochemistry can be very helpful in diagnosing SCLC in limited samples.

5,7

Nearly all SCLCs are positive for cytokeratin antibody mixtures with broad reactivity, such as AE1/AE3 and CAM5.2.

1,10

The majority of SCLCs are reactive to markers of neuroendocrine dierentiation, including CD56/NCAM, synaptophysin, and

chromogranin A. Fewer than 10% of SCLCs are negative for all neuroendocrine markers.

Thyroid transcription factor-1 (TTF-1) is positive in 85% to 90% of SCLCs.

11-14

• Ki-67 immunostaining can be very helpful in distinguishing SCLC from carcinoid tumors, especially in small biopsy samples with crushed or

necrotic tumor cells in which counting mitotic gures is dicult.

4,5

The Ki-67 proliferative index in SCLC is typically 50% to 100%.

References on

SCL-B 2 of 2

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Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

PRINCIPLES OF PATHOLOGIC REVIEW

References

Travis WD, Burke AP, Marx A, Nicholson AG. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. Lyon: IARC Press. 2015.

Travis WD, Brambilla E, Burke AP, et al. Introduction to The 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart. J Thorac

Oncol 2015;10:1240-1242.

Travis WD, Brambilla E, Nicholson AG, et al and WHO Panel. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and

Radiologic Advances Since the 2004 Classification. J Thorac Oncol 2015;10:1243-1260.

Pelosi G, Rindi G, Travis WD, Papotti M. Ki-67 antigen in lung neuroendocrine tumors: unraveling a role in clinical practice. J Thorac Oncol 2014;9:273-284.

Pelosi G, Rodriguez J, Viale G, Rosai J. Typical and atypical pulmonary carcinoid tumor overdiagnosed as small-cell carcinoma on biopsy specimens: a major pitfall in

the management of lung cancer patients. Am J Surg Pathol 2005;29:179-187.

Rindi G, Klersy C, Inzani F, et al. Grading the neuroendocrine tumors of the lung: an evidence-based proposal. Endocr Relat Cancer 2014;21:1-16.

Travis WD. Advances in neuroendocrine lung tumors. Ann Oncol 2010;21:vii65-vii71.

Zakowski MF. Pathology of small cell carcinoma of the lung. Semin Oncol 2003;30:3-8.

Nicholson SA, Beasley MB, Brambilla E, et al. Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with surgical specimens. Am J Surg Pathol

2002;26:1184-1197.

Masai K, Tsuta K, Kawago M, et al. Expression of squamous cell carcinoma markers and adenocarcinoma markers in primary pulmonary neuroendocrine carcinomas.

Appl Immunohistochem Mol Morphol 2013;21:292-2977.

Ordonez NG. Value of thyroid transcription factor-1 immunostaining in distinguishing small cell lung carcinomas from other small cell carcinomas. Am J Surg Pathol

2000;24:1217-1223.

Kaufmann O, Dietel M. Expression of thyroid transcription factor-1 in pulmonary and extrapulmonary small cell carcinomas and other neuroendocrine carcinomas of

various primary sites. Histopathology 2000;36:415-420.

Lantuejoul S, Moro D, Michalides RJ, et al. Neural cell adhesion molecules (NCAM) and NCAM-PSA expression in neuroendocrine lung tumors. Am J Surg Pathol

1998;22:1267-1276.

Wick MR. Immunohistology of neuroendocrine and neuroectodermal tumors. Semin Diagn Pathol 2000;17:194-203.

SCL-B

2 OF 2

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Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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Discussion

• Stage I–IIA SCLC is diagnosed in less than 5% of patients with SCLC.

• Patients most likely to benet from surgery are those with SCLC that is clinical stage I–IIA (T1–2,N0,M0) after standard staging evaluation

(including CT of the chest and upper abdomen, brain imaging, and PET/CT imaging).

1,2

Prior to resection, all patients should undergo mediastinoscopy or other surgical mediastinal staging to rule out occult nodal disease. This

may also include an endoscopic staging procedure.

For patients undergoing denitive surgical resection, the preferred operation is lobectomy with mediastinal lymph node dissection.

• Surgery may be considered for selected patients with T3 (based on size), N0 SCLC, if invasive mediastinal lymph node staging is negative.

• Patients who undergo complete resection should be treated with postoperative systemic therapy.

Patients without nodal metastases

should be treated with systemic therapy alone. Patients with N2 or N3 nodal metastases should be treated with postoperative concurrent

or sequential systemic therapy and mediastinal RT. Patients with N1 nodal metastases may be considered for postoperative mediastinal

radiation.

• The benet of PCI is unknown in patients who have undergone complete resection for pathologic stage I–IIA (T1–2,N0,M0) SCLC; consider

PCI or brain MRI surveillance for N0. These patients have a lower risk of developing brain metastases than patients with more advanced,

limited-stage SCLC, and may not benet from PCI.

However, PCI may have a benet in patients who are found to have pathologic stage

IIB or III SCLC after complete resection; therefore, PCI is recommended in these patients after adjuvant systemic therapy.

4,5

PCI is not

recommended in patients with poor performance status or impaired neurocognitive function.

SCL-C

Lad T, Piantadosi S, Thomas P, et al. A prospective randomized trial to determine the benefit of surgical resection of residual disease following response of small cell

lung cancer to combination chemotherapy. Chest 1994;106:320S-3S.

Yang CJ, Chan DY, Shah SA, et al. Long-term survival after surgery compared with concurrent chemoradiation for node-negative small cell lung cancer. Ann Surg

2018;268:1105-1112.

Yang CE, Chan DY, Speicher PJ, et al. Role of adjuvant therapy in a population-based cohort of patients with early-stage small-cell lung cancer. J Clin Oncol

2016;34:1057-1064.

Yang Y, Zhang D, Zhou X, et al. Prophylactic cranial irradiation in resected small cell lung cancer: a systematic review with meta-analysis. J Cancer 2018;9:433-439.

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.

Le Péchoux C, Dunant A, Senan S, et al. Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in

complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 9901): a randomised clinical trial. Lancet

Oncol 2009;10(5):467-474.

PRINCIPLES OF SURGICAL RESECTION

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Small Cell Lung Cancer

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and this illustration may not be reproduced in any form without the express written permission of NCCN.

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Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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Discussion

• Smoking cessation advice, counseling, and pharmacotherapy

Use the 5 A’s Framework: Ask, Advise, Assess, Assist, Arrange (https://www.ahrq.gov/prevention/guidelines/tobacco/5steps.html)

See NCCN Guidelines for Smoking Cessation

• Granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) is not recommended during

concurrent systemic therapy plus RT (category 1 for not using GM-CSF).

• Trilaciclib may be used as a prophylactic option to decrease the incidence of chemotherapy-induced myelosuppression when administered

before (or G-CSF may be administered after) platinum/etoposide ± immune checkpoint inhibitor-containing regimens or a topotecan-

containing regimen for extensive-stage small cell lung cancer (ES-SCLC).

• SIADH

Fluid restriction

Saline infusion for symptomatic patients

Antineoplastic therapy

Demeclocycline

Vasopressin receptor inhibitors (ie, conivaptan, tolvaptan) for refractory hyponatremia

• Cushing’s syndrome

Consider ketoconazole. If not eective, consider metyrapone.

Try to control before initiation of antineoplastic therapy.

• Leptomeningeal disease: See NCCN Guidelines for Central Nervous System Cancers

• Pain management: See NCCN Guidelines for Adult Cancer Pain

• Nausea/vomiting: See NCCN Guidelines for Antiemesis

• Psychosocial distress: See NCCN Guidelines for Distress Management

• See NCCN Guidelines for Palliative Care as indicated

SCL-D

PRINCIPLES OF SUPPORTIVE CARE

Bunn PA, Crowley J, Kelly K, et al. Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell

lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol 1995;13:1632-1641.

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

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and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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Discussion

PRINCIPLES OF SYSTEMIC THERAPY

PRIMARY OR ADJUVANT THERAPY FOR LIMITED STAGE SCLC:

Four cycles of systemic therapy are recommended.

Planned cycle length should be every 21–28 days during concurrent RT.

During systemic therapy + RT, cisplatin/etoposide is recommended (category 1).

The use of myeloid growth factors is not recommended during concurrent systemic therapy plus RT

(category 1 for not using GM-CSF).

Preferred Regimens

• Cisplatin 75 mg/m

day 1 and etoposide 100 mg/m

days 1, 2, 3

• Cisplatin 60 mg/m

day 1 and etoposide 120 mg/m

days 1, 2, 3

Other Recommended Regimens

• Cisplatin 25 mg/m

days 1, 2, 3 and etoposide 100 mg/m

days 1, 2, 3

• Carboplatin AUC 5–6 day 1 and etoposide 100 mg/m

days 1, 2, 3

a,4

PRIMARY THERAPY FOR EXTENSIVE-STAGE SCLC:

Four cycles of therapy are recommended, but some patients may receive up to 6 cycles based on response and tolerability after 4 cycles.

Preferred Regimens

• Carboplatin AUC 5 day 1 and etoposide 100 mg/m

days 1, 2, 3 and atezolizumab 1,200 mg day 1

every 21 days x 4 cycles followed by maintenance atezolizumab 1,200 mg day 1, every 21 days (category 1, for all)

b,5

• Carboplatin AUC 5–6 day 1 and etoposide 80–100 mg/m

days 1, 2, 3 and durvalumab 1,500 mg day 1 every 21 days x 4 cycles followed by

maintenance durvalumab 1,500 mg day 1 every 28 days (category 1 for all)

b,6

• Cisplatin 75–80 mg/m

day 1 and etoposide 80–100 mg/m

days 1, 2, 3 and durvalumab 1,500 mg day 1 every 21 days x 4 cycles followed by

maintenance durvalumab 1,500 mg day 1 every 28 days (category 1 for all)

b,6

Other Recommended Regimens

• Carboplatin AUC 5–6 day 1 and etoposide 100 mg/m

days 1, 2, 3

• Cisplatin 75 mg/m

day 1 and etoposide 100 mg/m

days 1, 2, 3

• Cisplatin 80 mg/m

day 1 and etoposide 80 mg/m

days 1, 2, 3

• Cisplatin 25 mg/m

days 1, 2, 3 and etoposide 100 mg/m

days 1, 2, 3

Useful In Certain Circumstances

• Carboplatin AUC 5 day 1 and irinotecan 50 mg/m

days 1, 8, 15

• Cisplatin 60 mg/m

day 1 and irinotecan 60 mg/m

days 1, 8, 15

• Cisplatin 30 mg/m

days 1, 8 and irinotecan 65 mg/m

days 1, 8

Cisplatin contraindicated or not tolerated.

Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease

and/or concurrent use of immunosuppressive agents.

SCL-E

1 OF 5

Subsequent Systemic Therapy (SCL-E 2 of 4)

Response Assessment (SCL-E 3 of 4)

References

(SCL-E 4 of 4)

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Small Cell Lung Cancer

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and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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Discussion

SCLC SUBSEQUENT SYSTEMIC THERAPY:

Relapse ≤6 months

PS 0–2

Preferred Regimens

• Topotecan PO or IV

14-16

• Lurbinectedin

• Clinical trial

Other Recommended Regimens

• Paclitaxel

22,23

• Docetaxel

• Irinotecan

• Temozolomide

26,27

• Cyclophosphamide/doxorubicin/vincristine (CAV)

• Oral etoposide

28,29

• Vinorelbine

30,31

• Gemcitabine

32,33

• Bendamustine (category 2B)

• Nivolumab

b,d,17,18

(category 3)

• Pembrolizumab

b,d,19,20,21

(category 3)

Relapse >6 months

Preferred Regimens

• Original regimen

d,35,36

Other Recommended Regimen

• Lurbinectedin

Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or concurrent use of

immunosuppressive agents.

Subsequent systemic therapy refers to second-line and beyond therapy.

Regimen not recommended for relapsed disease in patients on maintenance atezolizumab or durvalumab at time of relapse.

PRINCIPLES OF SYSTEMIC THERAPY

SCL-E

2 OF 5

Consider dose reduction or growth factor support for patients with PS 2.

References

(SCL-E 4 of 4)

Response Assessment (SCL-E 3 of 4)

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and this illustration may not be reproduced in any form without the express written permission of NCCN.

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Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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Discussion

Response Assessment

• Limited stage

For patients receiving adjuvant therapy, response assessment should occur only after completion of adjuvant therapy; do not repeat scans

to assess response during adjuvant treatment.

Response assessment after adjuvant therapy involves chest/abdomen/pelvic CT with contrast and brain MRI (preferred) with contrast or

brain CT with contrast (see SCL-6).

For patients receiving systemic therapy + concurrent RT, response assessment should occur only after completion of initial therapy; do not

repeat scans to assess response during initial treatment.

For patients receiving systemic therapy alone or sequential systemic therapy followed by RT, response assessment by chest/abdomen/

pelvis CT with contrast should occur after every 2 cycles of systemic therapy and at completion of therapy.

• Extensive stage

During systemic therapy, response assessment by chest/abdomen/pelvis CT with contrast should occur after every 2–3 cycles of systemic

therapy and at completion of therapy.

For patients with asymptomatic brain metastases receiving systemic therapy before brain RT, brain MRI (preferred) or CT with contrast

should be repeated after every 2 cycles of systemic therapy and at completion of therapy.

• Subsequent systemic therapy

Response assessment by chest/abdomen/pelvis CT with contrast should occur after every 2–3 cycles of systemic therapy.

PRINCIPLES OF SYSTEMIC THERAPY

SCL-E

3 OF 5

References

(SCL-E 4 of 4)

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

Bunn PA, Crowley J, Kelly K, et al. Chemoradiotherapy with or without

granulocyte-macrophage colony-stimulating factor in the treatment of limited-

stage small-cell lung cancer: a prospective phase III randomized study of the

Southwest Oncology Group. J Clin Oncol 1995;13:1632-1641.

Faivre-Finn C, Snee M, Ashcroft L, et al. Concurrent once-daily versus twice-

daily chemoradiotherapy in patients with limited-stage small-cell lung cancer

(CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol

2017;18:1116-1125.

Turrisi AT 3rd, Kim K, Blum R, et al. Twice-daily compared with once-daily thoracic

radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin

and etoposide. N Engl J Med 1999;340(4):265-271.

Skarlos DV, Samantas E, Briassoulis E, et al. Randomized comparison of early

versus late hyperfractionated thoracic irradiation concurrently with chemotherapy

in limited disease small-cell lung cancer: a randomized phase II study of the

Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol 2001;12(9):1231-

1238.

Horn L, Mansfield A, Szczęsna A, et al. First-line atezolizumab plus chemotherapy

in extensive-stage small-cell lung cancer. N Engl J Med 2018;379:2220-2229.

6Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide

versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung

cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet

2019;394:1929-1939.

Okamoto H, Watanabe K, Nishiwaki Y, et al. Phase II study of area under the

plasma-concentration-versus-time curve-based carboplatin plus standard-dose

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1999;17(11):3540-3545.

Spigel DR, Townley PM, Waterhouse DM, et al. Randomized phase II study

of bevacizumab in combination with chemotherapy in previously untreated

extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin

Oncol 2011;29:2215-2222.

Niell HB, Herndon JE, Miller AA, et al. Randomized phase III Intergroup trial

of etoposide and cisplatin with or without paclitaxel and granulocyte-colony

stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer

and Leukemia Group B trial 9732. J Clin Oncol 2005;23:3752-3759.

Evans WK, Shepherd FA, Feld R, et al. VP-16 and cisplatin as first-line therapy

for small-cell lung cancer. J Clin Oncol 1985;3(11):1471-1477.

Schmittel A, Fischer von Weikersthal L, Sebastian M, et al. A randomized phase

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667.

Noda K, Nishiwaki Y, Kawahara M, et al. Irinotecan plus cisplatin compared

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Hanna N, Bunn Jr. PA, Langer C, et al. Randomized phase III trial comparing

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von Pawel J, Schiller JH, Shepherd FA, et al. Topotecan versus

cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent

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O’Brien ME, Ciuleanu TE, Tsekov H, et al. Phase III trial comparing supportive

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Eckardt JR, von Pawel J, Pujol JL, et al. Phase III study of oral compared with

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Antonia SJ, López-Martin JA, Bendell J, et al. Nivolumab alone and nivolumab

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Chung HC, Lopez-Martin JA, Kao S, et al. Phase 2 study of pembrolizumab in

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Smit EF, Fokkema E, Biesma B, et al. A phase II study of paclitaxel in heavily

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SCL-E

4 OF 5

PRINCIPLES OF SYSTEMIC THERAPY

References

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

Yamamoto N, Tsurutani J, Yoshimura N, et al. Phase II study of weekly paclitaxel for relapsed and refractory small cell lung cancer. Anticancer Res 2006;26:777-781.

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Einhorn LH, Pennington K, McClean J. Phase II trial of daily oral VP-16 in refractory small cell lung cancer: a Hoosier Oncology Group study. Semin Oncol

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Johnson DH, Greco FA, Strupp J, et al. Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin

Oncol 1990;8:1613-1617.

Jassem J, Karnicka-Mlodkowska H, van Pottelsberghe C, et al. Phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients. EORTC

Lung Cancer Cooperative Group. Eur J Cancer 1993;29A:1720-1722.

Furuse K, Kuboa K, Kawahara M, et al. Phase II study of vinorelbine in heavily previously treated small cell lung cancer. Japan Lung Cancer Vinorelbine Study Group.

Oncology 1996;53:169-172.

Van der Lee I, Smit EF, van Putten JW, et al. Single-agent gemcitabine in patients with resistant small-cell lung cancer. Ann Oncol 2001;12:557-561.

Masters GA, Declerck L, Blanke C, et al. Phase II trial of gemcitabine in refractory or relapsed small-cell lung cancer: Eastern Cooperative Oncology Group Trial 1597.

J Clin Oncol 2003;21:1550-1555.

Lammers PE, Shyr Y, Li CI, et al. Phase II study of bendamustine in relapsed chemotherapy sensitive or resistant small-cell lung cancer. J Thorac Oncol 2014;9:559-

562.

Postmus PE, Berendsen HH, van Zandwijk N, et al. Retreatment with the induction regimen in small cell lung cancer relapsing after an initial response to short term

chemotherapy. Eur J Cancer Clin Oncol 1987;23:1409-1411.

Giaccone G, Ferrati P, Donadio M, et al. Reinduction chemotherapy in small cell lung cancer. Eur J Cancer Clin Oncol 1987;23:1697-1699.

37 Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial.

Lancet Oncol 2020;21:645-654.

SCL-E

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PRINCIPLES OF SYSTEMIC THERAPY

References

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

SCL-F

1 OF 5

See Limited Stage (cont.), Extensive Stage, Normal Tissue Dose Constraints, Prophylactic Cranial Irradiation (SCL-F 2 of 5)

PRINCIPLES OF RADIATION THERAPY

General Principles:

• General principles of RT for lung cancer—including commonly used abbreviations; standards for clinical and technologic expertise and quality

assurance; and principles of RT simulation, planning, and delivery—are provided in the NCCN Guidelines for Non-Small Cell Lung Cancer (see

NSCL-C) and are applicable to RT for SCLC.

• RT has a potential role in all stages of SCLC, as part of either denitive or palliative therapy. Radiation oncology input, as part of a multidisciplinary

evaluation or discussion, should be provided for all patients early in the determination of the treatment strategy.

• To maximize tumor control and to minimize treatment toxicity, critical components of modern RT include appropriate simulation, accurate target

denition, conformal RT (CRT) planning, and ensuring accurate delivery of the planned treatment. A minimum standard is CT-planned 3D-CRT

conformal RT. Multiple elds should be used, with all elds treated daily.

• Use of more advanced technologies is appropriate when needed to deliver adequate tumor doses while respecting normal tissue dose constraints.

Such technologies include (but are not limited to) 4D-CT and/or PET/CT simulation, intensity-modulated RT (IMRT)/volumetric modulated arc therapy

(VMAT), image-guided RT (IGRT), and motion management strategies. IMRT is preferred over 3D conformal EBRT on the basis of reduced toxicity in

the setting of concurrent chemotherapy/RT.

Quality assurance measures are essential and are covered in the NCCN Guidelines for Non-Small Cell

Lung Cancer (see NSCL-C).

• Useful references include the ACR Appropriateness Criteria at: http://www.acr.org/quality-safety/appropriateness-criteria

General Treatment Information:

• Limited stage:

In patients with clinical stage I–IIA (T1–2,N0,M0) who have undergone lobectomy and are found to have regional nodal involvement on nal

pathology, postoperative RT is recommended in pathologic N2 and may be considered in pathologic N1 stage, either sequentially or concurrently

with chemotherapy. Principles of postoperative RT for NSCLC, including target volumes and doses, are recommended.

Selected patients with stage I–IIA (T1–2,N0,M0) SCLC who are medically inoperable or in whom a decision is made not to pursue surgery may be

candidates for stereotactic ablative RT (SABR) to the primary tumor followed by adjuvant systemic therapy. Principles of SABR for SCLC are similar

to those for NSCLC (see NCCN Guidelines for Non-Small Cell Lung Cancer: NSCL-C).

2-4

Timing: RT concurrent with systemic therapy is standard and preferred to sequential chemo/RT.

RT should start early, with cycle 1 or 2 of systemic

therapy (category 1).

A shorter time from the start of any therapy to the end of RT (SER) is signicantly associated with improved survival.

Target denition: RT target volumes should be dened based on the pretreatment PET scan and CT scan obtained at the time of RT planning. PET/

CT should be obtained, preferably within 4 weeks and no more than 8 weeks, before treatment. Ideally, PET/CT should be obtained in the treatment

position.

Historically, clinically uninvolved mediastinal nodes have been included in the RT target volume, whereas uninvolved supraclavicular nodes

generally have not been included. Consensus on elective nodal irradiation (ENI) is evolving.

Several more modern series, both retrospective and

prospective, suggest that omission of ENI results in low rates of isolated nodal recurrences (0%–11%, most <5%), particularly when incorporating

PET staging/target denition (1.7%–3%).

9-14

ENI has been omitted in current prospective clinical trials (including CALGB 30610/RTOG 0538 and the

EORTC 08072 [CONVERT] trial). Inclusion of the ipsilateral hilum in the target volume, even if not grossly involved, diers between these trials but

may be reasonable.

References

(SCL-F 4 of 5)

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

• Limited stage (cont.):

In patients who start systemic therapy before RT, the gross tumor volume (GTV) can be limited to the post-induction systemic therapy volume to

avoid excessive toxicity. Initially involved nodal regions (but not their entire pre-systemic therapy volume) should be covered.

11,15

Dose and schedule: For limited-stage SCLC, the optimal dose and schedule of RT have not been established.

◊ Based on the randomized phase III trial, INT 0096, 45 Gy in 3 weeks (1.5 Gy twice daily [BID]) is superior (category 1) to 45 Gy in 5 weeks (1.8 Gy

daily).

16,17

When BID fractionation is used, there should be at least a 6-hour interfraction interval to allow for repair of normal tissue.

◊ If using once-daily RT, higher doses of 60–70 Gy should be used.

18-21

The current randomized trial CALGB 30610/RTOG 0538 is comparing the

standard arm of 45 Gy (BID) in 3 weeks to 70 Gy in 7 weeks. The randomized, phase III European CONVERT trial did not demonstrate superiority

of 66 Gy (once daily) over 45 Gy (BID), but overall survival and toxicity were comparable.

• Extensive stage:

Consolidative thoracic RT is benecial for selected patients with extensive-stage SCLC with complete response or good response to systemic

therapy, especially with residual thoracic disease and low-bulk extrathoracic metastatic disease. Studies have demonstrated that consolidative

thoracic RT up to denitive doses is well-tolerated, results in fewer symptomatic chest recurrences, and improves long-term survival in some

patients.

23,24

The Dutch CREST randomized trial of modest-dose thoracic RT (30 Gy in 10 fractions) in patients with extensive-stage SCLC that

responded to systemic therapy demonstrated signicantly improved 2-year overall survival and 6-month progression-free survival, although the

protocol-dened primary endpoint of 1-year overall survival was not signicantly improved.

Subsequent exploratory analysis found the benet of

consolidative thoracic RT is limited to the majority of patients who had residual thoracic disease after systemic therapy.

Dosing and fractionation of consolidative thoracic RT should be individualized within the range of 30 Gy in 10 daily fractions to 60 Gy in 30 daily

fractions, or equivalent regimens in this range.

Based on two randomized trials, immunotherapy during and after chemotherapy is a rst-line approach,

27,28

but these studies did not include

consolidative thoracic RT. Nevertheless, consolidative thoracic RT after chemoimmunotherapy can be considered for selected patients as above,

during or before maintenance immunotherapy (there are no data on optimal sequencing or safety).

Normal Tissue Dose Constraints:

• Normal tissue dose constraints depend on tumor size and location. For similar RT prescription doses, the normal tissue constraints used for NSCLC

are appropriate (see NSCL-C).

• When administering accelerated RT schedules (eg, BID) or lower total RT doses (eg, 45 Gy), more conservative constraints should be used. When

using accelerated schedules (eg, 3–5 weeks), the spinal cord constraints from the CALGB 30610/RTOG 0538 protocol should be used as a guide: ie,

the maximum spinal cord dose should be limited to ≤41 Gy (including scatter irradiation) for a prescription of 45 Gy BID in 3 weeks and limited to ≤50

Gy for more protracted schedules.

Prophylactic Cranial Irradiation:

• In patients with limited-stage SCLC (LS-SCLC) who have a good response to initial therapy, PCI decreases brain metastases and increases overall

survival (category 1)

29,30

In patients with extensive-stage SCLC (ES-SCLC) that has responded to systemic therapy, PCI decreases brain metastases.

A randomized trial conducted by the EORTC found improved overall survival with PCI.

However, a Japanese randomized trial found that in

patients who had no brain metastases on baseline MRI, PCI did not improve overall survival compared with routine surveillance MRI and treatment

of asymptomatic brain metastases upon detection.

Surveillance imaging for brain metastases is recommended for all patients regardless of PCI

status.

SCL-F

2 OF 5

PRINCIPLES OF RADIATION THERAPY

See Prophylactic Cranial Irradiation (cont.), Brain Metastases (SCL-F 3 of 5)

References

(SCL-F 4 of 5)

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

Prophylactic Cranial Irradiation (cont.):

• The preferred dose for PCI to the whole brain is 25 Gy in 10 daily fractions. A shorter course (eg, 20 Gy in 5 fractions) may be appropriate

in selected patients with extensive-stage disease. In a large randomized trial (PCI 99-01), patients receiving a dose of 36 Gy had higher

mortality and higher chronic neurotoxicity compared to patients treated with 25 Gy.

33,34

• Neurocognitive function: Increasing age and higher doses are the most predictive factors for development of chronic neurotoxicity. In trial

RTOG 0212, 83% of patients older than 60 years of age experienced chronic neurotoxicity 12 months after PCI versus 56% of patients

younger than 60 years of age (P = .009).

Concurrent systemic therapy and high total RT dose (>30 Gy) should be avoided in patients

receiving PCI.

• Administer PCI after resolution of acute toxicities of initial therapy. PCI is not recommended in patients with poor performance status or

impaired neurocognitive functioning.

• When administering PCI, consider adding memantine during and after RT, which has been shown to decrease neurocognitive impairment

following whole brain radiation therapy (WBRT) for brain metastases.

The dose of memantine used on RTOG 0614 was as follows: week

1 (starting on day 1 of WBRT), 5 mg each morning; week 2, 5 mg each morning and evening; week 3, 10 mg each morning and 5 mg each

evening; and weeks 4–24, 10 mg each morning and evening.

• Consider hippocampal-sparing PCI using IMRT.

36,37,38,39

• Current randomized trials are evaluating whether MRI surveillance alone is non-inferior to MRI surveillance plus PCI on overall survival and

whether hippocampal-sparing PCI reduces memory impairment compared to whole brain PCI in LS-SCLC and ES-SCLC.

Brain Metastases:

• Brain metastases should typically be treated with WBRT; however, selected patients with a small number of metastases may be appropriately

treated with stereotactic radiotherapy (SRT)/radiosurgery (SRS).

A current trial is comparing SRS to hippocampal-sparing WBRT plus

memantine in this setting.

• Recommended dose for WBRT is 30 Gy in 10 daily fractions. Consider adding memantine during and after RT (see Prophylactic Cranial

Irradiation for memantine dosing).

• In patients who develop brain metastases after PCI, repeat WBRT may be considered in carefully selected patients.

41,42

SRS is preferred, if

feasible.

43,44

• For patients with a better prognosis (eg, ≥4 months), hippocampal-sparing WBRT using IMRT plus memantine is preferred because it

produces less cognitive function failure than conventional WBRT plus memantine.

Palliative Radiation for Extracranial Metastases:

• Common radiation dose-fractionation regimens (eg, 30 Gy in 10 fractions, 20 Gy in 5 fractions, 8 Gy in 1 fraction) used for palliation of other

solid tumors are appropriate for palliation of SCLC metastases in most patients.

• Conformal techniques, such as IMRT, and/or higher dose intensity approaches, including SABR or SRS, may be appropriate in selected

patients (eg, tumors with close proximity to organs at risk, re-irradiation, or better prognosis).

SCL-F

3 OF 5

PRINCIPLES OF RADIATION THERAPY

References

(SCL-F 4 of 5)

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

Chun SG, Hu C, Choy H, et al. Impact of intensity-modulated radiation therapy

technique for locally advanced non-small-cell lung cancer: a secondary analysis of

the NRG Oncology RTOG 0617 randomized clinical trial. J Clin Oncol 2017;35:56-

62.

Shioyama Y, Onishi H, Takayama K, et al. Clinical outcomes of stereotactic body

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of the Japanese Radiological Society Multi-Institutional SBRT Study Group

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Verma V, Simone CB 2nd, Allen PK, Lin SH. Outcomes of stereotactic body

radiotherapy for T1-T2N0 small cell carcinoma according to addition of

chemotherapy and prophylactic cranial irradiation: a multicenter analysis. Clin

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Verma V, Simone CB 2nd, Allen PK, et al. Multi-institutional experience of

stereotactic ablative radiation therapy for stage I small cell lung cancer. Int J

Radiat Oncol Biol Phys 2017;97:362-371.

Takada M, Fukuoka M, Kawahara M, 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;20:3054-3060.

Fried DB, Morris DE, Poole C, et al. Systematic review evaluating the timing of

thoracic radiation therapy in combined modality therapy for limited-stage small-cell

lung cancer. J Clin Oncol 2004;22:4837-4845.

De Ruysscher D, Pijls-Johannesma M, Bentzen SM, et al. Time between the first

day of chemotherapy and the last day of chest radiation is the most important

predictor of survival in limited-disease small-cell lung cancer. J Clin Oncol

2006;24:1057-1063.

Videtic GMM, Belderbos JSA, Kong F-MS, et al. Report from the International

Atomic Energy Agency (IAEA) consultants’ meeting on elective nodal irradiation

in lung cancer: small-cell lung cancer (SCLC). Int J Radiat Oncol Biol Phys

2008;72:327-334.

De Ruysscher D, Bremer RH, Koppe F, et al. Omission of elective node irradiation

on basis of CT-scans in patients with limited disease small cell lung cancer: a

phase II trial. Radiother Oncol 2006;80:307-312.

van Loon J, De Ruysscher D, Wanders R, et al. Selective nodal irradiation

on basis of (18)FDG-PET scans in limited-disease small-cell lung cancer: a

prospective study. Int J Radiat Oncol Biol Phys 2010;77:329-336.

Hu X, Bao Y, Zhang L, et al. Omitting elective nodal irradiation and irradiating

postinduction versus preinduction chemotherapy tumor extent for limited-stage

small cell lung cancer: interim analysis of a prospective randomized noninferiority

trial. Cancer 2012;118:278-287.

Shirvani SM, Komaki R, Heymach JV, et al. Positron emission tomography/

computed tomography-guided intensity-modulated radiotherapy for limited-stage

small-cell lung cancer. Int J Radiat Oncol Biol Phys 2012;82:e91-97.

Xia B, Chen G-Y, Cai X-W, et al. Is involved-field radiotherapy based on CT

safe for patients with limited-stage small-cell lung cancer? Radiother Oncol

2012;102:258-262.

Colaco R, Sheikh H, Lorigan P, et al. Omitting elective nodal irradiation during

thoracic irradiation in limited-stage small cell lung cancer - Evidence from a phase

II trial. Lung Cancer 2012;76:72-77.

Liengswangwong V, Bonner JA, Shaw EG, et al. Limited-stage small-cell lung

cancer: patterns of intrathoracic recurrence and the implications for thoracic

radiotherapy. J Clin Oncol 1994;12:496-502.

Turrisi AT, Kim K, Blum R, et al. Twice-daily compared with once-daily thoracic

radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin

and etoposide. N Engl J Med 1999;340:265-271.

Schild SE, Bonner JA, Shanahan TG, et al. Long-term results of a phase III trial

comparing once-daily radiotherapy with twice-daily radiotherapy in limited-stage

small-cell lung cancer. Int J Radiat Oncol Biol Phys 2004;59:943-951.

Choi NC, Herndon JE, Rosenman J, et al. Phase I study to determine the

maximum-tolerated dose of radiation in standard daily and hyperfractionated-

accelerated twice-daily radiation schedules with concurrent chemotherapy for

limited-stage small-cell lung cancer. J Clin Oncol 1998;16:3528-3536.

Miller KL, Marks LB, Sibley GS, et al. Routine use of approximately 60 Gy once-

daily thoracic irradiation for patients with limited-stage small-cell lung cancer. Int J

Radiat Oncol Biol Phys 2003;56:355-359.

Roof KS, Fidias P, Lynch TJ, et al. Radiation dose escalation in limited-stage

small-cell lung cancer. Int J Radiat Oncol Biol Phys 2003;57:701-708.

Bogart JA, Herndon JE, Lyss AP, et al. 70 Gy thoracic radiotherapy is feasible

concurrent with chemotherapy for limited-stage small-cell lung cancer: analysis

of Cancer and Leukemia Group B study 39808. Int J Radiat Oncol Biol Phys

2004;59:460-468.

Faivre-Finn C, Snee M, Ashcroft L, et al. Concurrent once-daily versus twice-

daily chemoradiotherapy in patients with limited-stage small-cell lung cancer

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2017;18:1116-1125.

SCL-F

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PRINCIPLES OF RADIATION THERAPY

References

(continued)

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

PRINCIPLES OF RADIATION THERAPY

References

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extensive stage small-cell lung cancer: a phase 3 randomised controlled trial.

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Slotman BJ, van Tinteren H, Praag JO, et al. Radiotherapy for extensive stage

small-cell lung cancer-Authors’ reply. Lancet 2015;385:1292-1293.

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chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med

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cancer in complete remission after chemotherapy and thoracic radiotherapy

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SCL-F

5 OF 5

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion

ST-1

Table 1 - Denition of small cell lung cancer consists of two stages:

(1) Limited-stage: Stage I-III (T any, N any, M0) that can be safely treated with denitive radiation doses. Excludes T3-4 due to multiple lung nodules that

are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan.

(2) Extensive-stage: Stage IV (T any, N any, M 1a/b/c), or T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is

too large to be encompassed in a tolerable radiation plan.

Table 2 - American Joint Committee on Cancer (AJCC) Eighth ed., 2017 Denitions of TNM

Continued

Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the AJCC Cancer Staging Manual, Eighth Edition

(2017) published by Springer International Publishing.

T Primary Tumor

TX Primary tumor cannot be assessed, or tumor proven by the presence of malignant cells in sputum or bronchial washings but not

visualized by imaging or bronchoscopy

T0 No evidence of primary tumor

Tis Carcinoma in situ

Squamous cell carcinoma in situ (SCIS)

Adenocarcinoma in situ (AIS): adenocarcinoma with pure lepidic pattern, ≤3 cm in greatest dimension

T1 Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more

proximal than the lobar bronchus (i.e., not in the main bronchus)

T1mi Minimally invasive adenocarcinoma: adenocarcinoma (≤3 cm in greatest dimension) with a predominantly lepidic pattern and ≤5 mm

invasion in greatest dimension

T1a Tumor ≤1 cm in greatest dimension. A supercial, spreading tumor of any size whose invasive component is limited to the bronchial

wall and may extend proximal to the main bronchus also is classied as T1a, but these tumors are uncommon.

T1b Tumor >1 cm but ≤2 cm in greatest dimension

T1c Tumor >2 cm but ≤3 cm in greatest dimension

T2 Tumor >3 cm but ≤5 cm or having any of the following features: (1) Involves the main bronchus, regardless of distance to the

carina, but without involvement of the carina; (2) Invades visceral pleura (PL1 or PL2); (3) Associated with atelectasis or obstructive

pneumonitis that extends to the hilar region, involving part or all of the lung. T2 tumors with these features are classied as T2a if ≤4

cm or if the size cannot be determined and T2b if >4 cm but ≤5 cm.

T2a Tumor >3 cm but ≤4 cm in greatest dimension

T2b Tumor >4 cm but ≤5 cm in greatest dimension

T3 Tumor >5 cm but ≤7 cm in greatest dimension or directly invading any of the following: parietal pleura (PL3), chest wall (including

superior sulcus tumors), phrenic nerve, parietal pericardium; or separate tumor nodule(s) in the same lobe as the primary

T4 Tumor >7 cm or tumor of any size invading one or more of the following: diaphragm, mediastinum, heart, great vessels, trachea,

recurrent laryngeal nerve, esophagus, vertebral body, or carina; separate tumor nodule(s) in an ipsilateral lobe dierent from that of

the primary

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

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Discussion

ST-2

Most pleural (pericardial) effusions with lung cancer are a result of the tumor. In a few patients, however, multiple microscopic examinations of pleural (pericardial) fluid are negative for

tumor, and the fluid is nonbloody and not an exudate. If these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a

staging descriptor.

Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the AJCC Cancer Staging Manual, Eighth Edition

(2017) published by Springer International Publishing.

Table 3. AJCC Prognostic Groups

T N M

Occult

carcinoma

TX N0 M0

Stage 0 Tis N0 M0

Stage IA1 T1mi N0 M0

T1a N0 M0

Stage IA2 T1b N0 M0

Stage IA3 T1c N0 M0

Stage IB T2a N0 M0

Stage IIA T2b N0 M0

Stage IIB T1a N1 M0

T1b N1 M0

T1c N1 M0

T2a N1 M0

T2b N1 M0

T3 N0 M0

Stage IIIA T1a N2 M0

T1b N2 M0

T1c N2 M0

T2a N2 M0

T2b N2 M0

T3 N1 M0

T4 N0 M0

T4 N1 M0

T N M

Stage IIIB T1a N3 M0

T1b N3 M0

T1c N3 M0

T2a N3 M0

T2b N3 M0

T3 N2 M0

T4 N2 M0

Stage IIIC T3 N3 M0

Stage IV

Any T

Any N

Stage IVA Any T Any N M1a

Any T Any N M1b

Stage IVB Any T Any N M1c

Table 2. Denitions for T, N, M (continued)

N Regional Lymph Nodes

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Metastasis in ipsilateral peribronchial and/or ipsilateral

hilar lymph nodes and intrapulmonary nodes, including

involvement by direct extension

N2 Metastasis in ipsilateral mediastinal and/or subcarinal

lymph node(s)

N3 Metastasis in contralateral mediastinal, contralateral hilar,

ipsilateral or contralateral scalene, or supraclavicular lymph

node(s)

M Distant Metastasis

MX Distant metastasis cannot be assessed

M0 No distant metastasis

M1 Distant metastasis

M1a Separate tumor nodule(s) in a contralateral lobe; tumor

with pleural or pericardial nodules or malignant pleural or

pericardial eusion

M1b Single extrathoracic metastasis in a single organ (including

involvement of a single nonregional node)

M1c Multiple extrathoracic metastases in a single organ or in

multiple organs

Prognostic Stage Groups

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

NCCN Guidelines Index

Table of Contents

Discussion

NCCN Categories of Evidence and Consensus

Category 1 Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2A Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2B Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.

Category 3 Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

All recommendations are category 2A unless otherwise indicated.

NCCN Categories of Preference

Preferred intervention

Interventions that are based on superior ecacy, safety, and evidence; and, when appropriate,

aordability.

Other recommended

intervention

Other interventions that may be somewhat less ecacious, more toxic, or based on less mature data;

or signicantly less aordable for similar outcomes.

Useful in certain

circumstances

Other interventions that may be used for selected patient populations (dened with recommendation).

All recommendations are considered appropriate.

CAT-1

NCCN Guidelines Version 3.2021

Small Cell Lung Cancer

(NCCN

and this illustration may not be reproduced in any form without the express written permission of NCCN.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

NCCN Guidelines Index

Table of Contents

Discussion