Non-Small Cell Lung Cancer:

Treatments That Work

Trevor Lever RN, MSN, OCN

Heather Smith MS, CMD, RT (R)(T)

Objectives

1. Define non-small cell lung cancer.

2. Discuss the risk factors for non-small cell lung cancer.

3. Discuss the signs and symptoms of non-small cell lung cancer.

4. Discuss different treatment options for non-small cell lung cancer.

5. Discuss the side effects of treatment.

Epidemiology Approximately 415,000 Americans living today have been diagnosed with

lung cancer at some point in their lives.

In 2016, an estimated 224,000 new lung cancer cases in the United States

– Representing 13% of all cancers.

Approximately 156,000 deaths from lung cancer.

In 2017, remains leading cause of death from cancer in both men and

women.

More deaths from lung cancer than colon, breast, and prostate combined.

Lung cancer’s 5-year survival rate (17.7%) is lower than other leading

cancer sites, such as colon (64.4%), breast (89.7%) and prostate (98.9%).

Albert & Samet, 2003, pp. 21-28

Albert & Samet, 2003, pp. 18-20

Diagnosis of Lung Cancer by Age

Albert & Samet, 2003, pp. 18-20

Albert & Samet, 2003, pp. 18-20

Lung Cancer Screening In 2013, the US Preventive Task Force recommended that people at high

risk for lung cancer undergo annual lung cancer screenings with low-dose

computed tomography.

Purpose: Annual LDCT screening can detect lung cancer at an early stage

in asymptomatic high-risk individuals. Lung cancer screening should be

thought of as a process rather than a single test.

Benefits vs. Harms

Patient Costs

Scientific Uncertainties

Alternatives

Richards, White, & Caraballa, 2014, pp.320-322

Lung Cancer Screenings

Who is eligible?

55-77 y/o.

Asymptomatic.

Current smoker or have quit smoking within the last 15 years.

Have a tobacco smoking history of at least 30 “pack years”

(an average of one pack a day for 30 years).

Written order from their physician or qualified non-physician

practitioner.

Richards, White, & Caraballa, 2014, pp.320-322

Definition

Any type of epithelial lung cancer other than small cell lung

cancer. Accounts for 85% of all lung cancers. Relatively

insensitive to chemotherapy, compared to small cell

carcinoma. Primarily treated by surgical resection with

curative intent (Stage I & II).

Lilenbaum, Jett, & Vora,, 2017, pp. 12-14

Histology

25% - 30% - Squamous Cell Carcinoma

30% - 35% - Adenocarcinoma

10% - 15% - Large Cell Carcinoma

Penfold, 2012 , pp. 7-8

Risk Factors

Smoking (major cause)

Genetics

Radon, non-industrial air pollution, industrial

exposure to chemicals

Asbestos

Mannino, Stoller, Midthun, & Vora, 2017, pp. 25-28

Signs and Symptoms

Cough – 50% to 70%

Hemoptysis – 25% to 50%

Dyspnea – 25%

Chest Pain – 20%

Usually present with suggestive metastatic disease

(skeletal pain/neurological signs & symptoms)

Pancoast Syndrome

Horner Syndrome

Hypercalcemia

Thomas & Gould, 2017, p. 15

Medical Management – Initial Workup

Thorough history

Physical examination/Neurologic examination

Radiologic studies

Lab studies

Pathologic evaluation of specimens

Staging

Thomas & Gould, 2017, p. 16-17

Thomas & Gould, 2017, p. 16-17

Thomas & Gould, 2017, p. 16-17

Stage 0. The cancer has not spread beyond the inner lining of

the lung.

Stage I. The cancer is small and has not spread to the lymph

nodes.

Stage II. The cancer has spread to some lymph nodes near the

original tumor.

Stage III. The cancer has spread to nearby tissue or to far away

lymph nodes.

Stage IV. The cancer has spread to other organs of the body,

such as the other lung, brain, or liver.

Stages

Thomas & Gould, 2017, p. 16-17

Thomas & Gould, 2017, p. 16-17

Treatment Algorithm for NSCLC

Pneumonectomy

Segmentectomy

LobectomySleeve Lobectomy

Wedge Resection

Treatment Strategies: SurgeryWest, Vallieres, & Schild, 2017, pp. 25-28

Treatment Strategies

Chemotherapy

Targeted Therapy/Immunotherapy

Chemotherapy

Neoadjuvant/Adjuvant/Concurrent therapy

Combination of 2 chemo drugs

Cisplatin, Carboplatin, Taxol, Abraxane, Taxotere,

Gemzar, Navelbine, Camptosar, Etoposide,

Vinblastine, Alimta

Lilenbaum, Jett, & Vora,, 2017, pp. 18-25

Chemotherapy: Side Effects Hair Loss

Mouth Sores

Loss of Appetite

Nausea and Vomiting

Diarrhea or Constipation

Infection

Easy Bruising or Bleeding

Fatigue

Peripheral Neuropathy

Lilenbaum, Jett, & Vora,, 2017, pp. 18-25

Targeted Therapy: Target Blood Vessel Growth

Avastin (bevacizumab)

Cyramza (ramucirumab)

**Targets VEGF**

(Vascular Endothelial Growth Factor)

**Prevents formation of new blood

vessels**

Lilenbaum, Jett, Schild, & Vora,, 2017, pp. 20-24

Side Effects: Avastin or Cyramza

High Blood Pressure

Fatigue

Bleeding

Low WBCs

Headaches

Mouth Sores

Loss of Appetite

Diarrhea

Perforations

Lilenbaum, Jett, Schild, & Vora,, 2017, pp. 20-24

Targeted Therapy: Drugs That Target Cells with

EGFR Changes

Tarceva (erolotinib)

Gilotrif (afatinib)

Iressa (gefitinib)

Tagrisso (osimertinib)

Portrazza (necitumunab)

**Targets Epidermal Growth Factor s

(EGRF)**

Lilenbaum, Jett, Schild, & Vora,, 2017, pp. 20-24

Side Effects: EGFR Inhibitors

Skin problems

Diarrhea

Mouth Sores

Loss of Appetite

Hepatotoxicity

Renal Failure

GI Perforation

Ocular Disorders

Embryo-Fetal Toxicity

QT Prolongation/Cardiomyopathy (Tagrisso)

Lilenbaum, Jett, Schild, & Vora,, 2017, pp. 20-24

Toxicity Management with EGFR Inhibitors

Rash: moisturize the skin twice daily, avoid hot showers, do not use products that are drying. For mild rash, use topical hydrocortisone or clindamycin 1% gel. For moderate rash, topical hydrocortisone, oral doxycycline or minocycline. If grade 3 or 4 rash occurs, hold treatment until improvement to grade 1, then titrate dosing.

Diarrhea: begin with diet changes, then use loperamide or lomotil. If diarrhea reaches a grade 3 , dosing is held. Emphasize the importance of good hydration.

Lilenbaum, Jett, Schild, & Vora,, 2017, pp. 20-24

Targeted Therapy: Drugs That Target Cells With

ALK Gene Changes

Xalkori (crizotinib)

Zykadia (ceritinib)

Alecensa (alectinib)

**ALK (anaplastic lymphoma kinase) gene rearrangement

produces an abnormal ALK protein (mutation) that causes the

cells to grow and spread.**

Lilenbaum, Jett, Schild, & Vora,, 2017, pp. 20-24

Side Effects: ALK Inhibitors

Nausea & Vomiting

Diarrhea

Constipation

Fatigue

Changes in Vision

Lilenbaum, Jett, Schild, & Vora,, 2017, pp. 20-24

Immunotherapy

Opdivo (nivolumab)

Keytruda (pembrolizumab)

*Target PD-1 receptors*

Lilenbaum, Jett, Schild, & Vora,, 2017, pp. 20-24

Side Effects: Immunotherapy

Flu-like symptoms

Fatigue

Rashes

Fever

Drops in blood pressure

Colitis

Pneumonitis

Hepatitis

Nephritis

Encephalitis

Lilenbaum, Jett, Schild, & Vora,, 2017, pp. 20-24

Management of Immune Related Reactions

Lilenbaum, Jett, Schild, & Vora,, 2017, pp. 20-24

Treatment Strategies

Radiation Therapy

Radiation Therapy

Simulation

Treatment Planning

Treatment Delivery

Simulation

LUNG SIMULATION

Retrospective Gating

Copyright ©2007, Varian Medical Systems, Inc. All rights reserved.

Isocenter Markings

Simple?—Not really

Treatment Planning(Medical Dosimetry)

Certified Medical Dosimetrists or Radiation Physicists

Treatment Algorithm for NSCLCThomas & Gould, 2017, p. 16-17

Appropriate staging and workup is vital prior to making treatment decisions

Stage I-II:◦ SBRT often a good alternative for non operable candidates if node negative

Stage IIIA◦ RT may be used after surgery, before surgery, or in lieu of surgery (50.4-54Gy)

Stage IIIB◦ RT and chemotherapy standard of care

◦ Concurrent has better outcomes than sequential but more toxic

◦ Need at least 60Gy

◦ Going above 60Gy is controversial and not standard

Stage IV◦ Palliative RT for brain metastases, bone mets, or obstructing central mass

SABR Fractionation Schedules NCCN 2016

Early Stage Medically Inoperable

Stereotactic Body Radiotherapy (SBRT)◦ AKA Stereotactic Radiosurgery (SRS)

◦ AKA Stereotactic Ablative Body Radiotherapy (SABR)

◦ Local Control: 90%

◦ Overall Survival at 5 years: approximately 50%

Conventionally fractionated radiotherapy◦ i.e. 60 Gray (Gy) in 30 fractions (or treatments)

◦ Better than no treatment, but not great results

◦ Median Overall survival: 1 year

◦ Local Control for stage I-II tumors: estimated 60% in 5 years

Lung Cancer Diagnosis

Do they need treatment?

◦ YES.

◦ Untreated lung cancer patients live on average for 7.15 months.

◦ Lung cancer is considered a terminal illness with a five-year survival rate of about 16%

Deductive Reasoning

Treatment Planning System

Retrospective Gating

Copyright ©2007, Varian Medical Systems, Inc. All rights reserved.

Removing Motion Artifacts

More Tumor Definition

Gating System

Motion ChartTracking signal

Gating interval set

using phase thresholdsGating interval

mapped to motion plot

Treatment

Beam On

Sui Shen, Ph.D.

AVG 30-70

MIP 30-70

SBRT Lung

SBRT LUNG

Comparison

Gated VMAT

Treatment

Treatment Console

Linear Accelerator

LUNG RADIOSURGERY TREATMENT

KV ORTHO SET CBCT

Beam Off, Beam On

LUNG SBRT FIDUCIALS

Imaging and Treatment

TRIGGERED IMAGING

Triggered images rate by:◦ Every expiration

◦ Gantry angle

◦ Amount of MU delivered

5mm margin circle follows fiducials in 360 degrees◦ Fiducials must fall within margin

Hold beam if out

LUNG SBRT TRIGGERED IMAGING

Future Trend??

SBRT for Surgically Operable Patients, not just inoperable patients.

References

Alberg, A., & Samet, J (2003). Epidemiology of Lung Cancer. Retrieved March 27, 2017 from

www.chestjournal.org

Welch, H.G., Wlolshin, S., Schwartz, L.M., Gordis, L., Getzche, P.C., Harris, R., Kramer, B.S.,

& Ramsphoff, D.F. (2007). Overstating evidence for lung cancer screening: The

International Early Lung Cancer Action Program Study. Retrieved March 26, 2017 from

www.archinternmed.com

Lilenbaum, R,C., Jett, J.R., & Vora (2017). Advanced non-small cell lung cancer: Subsequent systemic

therapy for previous treated patients. Retrieved March 29. 2017 from

www.uptodate.com

Thomas, K.W., & Gould, M.K. (2017). Overview of the initial evaluation, diagnosis, and staging of patients

with suspected lung cancer. Retrieved April 5, 2017 from www.uptodate.com

Thomas, R.B., White, M.C., & Caraballo (2014). Lung cancer screening with low-dose computed tomography

primary care providers. Retrieved March 31, 2017 from www.primarycare.theclinics.com

Mannino, D.M., Stoller, J.K., Midthun, D.E., Vora, S.R. (2017). Cigarette smoking and other possible risk

factors for lung cancer. Retrieved March 31, 2017 from www.uptodate.com

References (cont)

Herbst, R., Bajorin, D.F., Bleiberg, H., Blum, D., Hao, D., Johnson, B.E., Ozols, R.F., Demetri,

G.D., Ganz, P.A., Kris, M.G., Levin, B., Markman, M., Raghavan, D., Reaman, G.H.,

Sawaya, R., Schuchter, L.M., Sweetenham, J.W., Vahdat, L.T., Vokes, E.E., Winn, R.J., &

Mayer, R.J. (2006). Clinical cancer advances 2005: Major research advances in cancer

treatment, prevention, and screening – a report from the American Society of Clinical

Oncology, Journal of Clinical Oncology, 24(1), 190-205.

Wsst, H.J.., Vallieres, E., Schild, S.E. (2017). Management of stage I and stage II non-small cell

lung cancer. Retrieved April 7, 2017 form www.uptodate.com