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