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Melody Mendenhall, RN, MSN, NP-CUCLA Hematology and Oncology
Lung Cancer/Phase I Clinical Trials Team
MANAGEMENT OF LUNG CANCER
OBJECTIVES
Identify the incidence of lung cancer in the US Identify risk factors associated with lung cancer Review Diagnostic Techniques/Staging Distinguish the different histological types of
lung cancer Discuss standard treatment/novel therapy Identify nursing implications in a patient with
lung cancer
ANATOMY OF THE LUNGS
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LYMPH NODES
Lung cancer is the most common cause of cancer death in the US and worldwide
Around 160,000 will die of lung cancer in 2016
1 in 7 smokers will die of lung cancer 1 year survival – <50% overall 5 year survival – 17% overall
BACKGROUND
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RISK FACTORS
• SMOKING• SECOND HAND SMOKE• OCCUPATIONAL EXPOSURE
• ASBESTOS• RADON
• PAST MEDICAL HISTORY• CELL MUTATIONS• CHRONIC LUNG DISEASE
SCREENING
• Based on National Lung Cancer Screening Trial
• 55-74 years old• 30 pack-year smoking
history• Current smoker or quit
within 15 years• Annual low-dose chest
CT scan
CLINICAL PRESENTATION
PRIMARY TUMOR/INTRATHORACIC SPREAD Asymptomatic Cough Shortness of breath Chest DiscomfortHemoptysis Pancoast Tumor/Horner’s Syndrome SVCO/SVCS Laryngeal Nerve Paralysis
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CLINICAL PRESENTATION
EXTRATHORACIC SPREAD Palpable Lymph nodesBone Pain/Fracture Liver Enzyme Abnormalities/Jaundice Focal Neuro deficits/seizures/confusion/headache Spinal Cord Compression**Weight Loss/Fatigue/Fever/Anorexia
ONCOLOGIC EMERGENCY: SVCS
Obstruction of SVC Facial/Neck Swelling,
neck vein distension, *dyspnea, lightheadedness, nausea
CT chest Treatment: Radiation,
chemotherapy, anticoagulation, vascular stent
ONC EMERGENCY: PULMONARY EMBOLISM
Hypercoaguable state in patients with metastatic lung cancer
Presentation: Dyspnea, sudden onset cough, chest pain, tachypnea, tachycardia
CT Angiogram is standard for dx Treatment with thrombolytics (?),
anticoagulation. Anticoagulation for six months.
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ONC EMERGENCY: SPINAL CORD COMPRESSION
Presentation: Back pain, radiating pain, lower extremity weakness, loss of sensation, loss of bowel or bladder control
MRI is standard testing Treat with radiation/surgery
ONCOLOGIC EMERGENCY: HYPERCALCEMIA
Osteolytic metastases, parathyroid hormone related peptide (PTHrP), tumor secretion of 1, 25 dihydroxyvitamin D (lymphomas)
Altered mental status, constipation, abdominal pain, polyuria, polydypsia, fatigue, muscle weakness, nausea, anorexia
Mild: <12mg/dL; Moderate 12-14mg/dL, severe >14mg/dL
Other labs: PTHrP, Ca++, PTH, Vitamin D Treatments: Saline (with or without diuretics),
calcitonin, bisphosphonates, denosumab, dialysis
ONCOLOGIC EMERGENCY: SIADH
ADH increased by tumor production of ADH, pulmonary disease, pain, drugs
Renal tubules more permeable to H20, decreased urine output, increased urine sodium, increased urine osmolality. Results in increased blood volume, dilutional hyponatremia
Confusion, fatigue, lethargy, seizures Treat with fluid restriction, saline, hypertonic
saline, treating underlying condition
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DIAGNOSTICS
CXR, CT Scan, PET/CT Imaging of Brain- MRI Needle Biopsy, Bronchoscopy, Thoracentesis,
VATS, biopsy of metastatic lesion Mediastinoscopy
Lung Cancer Subtypes
Non-Small Cell Lung Cancer
(NSCLC) ~85%
http://www.nci.nih.gov/cancertopics/pdq/treatment/non-small-cell-lung. Accessed 02/05/07.
Small Cell Lung
Cancer(SCLC) ~15%
Large Cell Carcinoma10%-15%
Adenocarcinoma35%-40%
Squamous Cell Carcinoma25%-30%
SMALL CELL LUNG CANCER
One Side of the Lung Ipsilateral Lymph nodes 1/3 Small Cell Cancers Presentation
Cough Shortness of breath Fatigue Weight Loss/Anorexia *SVCS
LIMITED STAGE EXTENSIVE STAGE
Both sides of the lungs Contralateral Lymph nodes Distant Metastasis 2/3 Small Cell Cancers Presentation
Limited stage Symptoms Jaundice Pain *Weight Loss/Anorexia Stridor Pain/Fracture Neurological Symptoms Blood Clot
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SMALL CELL LUNG CANCER TREATMENT
Rare patients are surgical candidates, small tumor size
Cisplatin and Etoposide 2nd line topotecan, irinotecan, nivolumab +/-
ipilumumab (now part of NCCN guidelines) For limited stage disease, combine with
radiation Prophylactic whole brain radiotherapy in limited
stage patients with complete response
NSCLC
Adenocarcinoma 35-40% Driving mutations are most commonly found in
adenocarcinomas Squamous Cell Carcinoma
25-30% Large Cell Carcinoma/NSCL NOS
10-15 Treatments vary widely depending on
staging/histology/molecular testing- constantly evolving
TNM STAGING
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TNM STAGING
TNM STAGING
STAGE I-II NSCLC
Surgery Radiation is an option, for patients who are not
surgical candidates Adjuvant therapy, chemotherapy for stage II and
high-risk IB (large tumor size, vascular invasion, unknown lymph node status)
Radiation for patients with positive surgical margins
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ADJUVANT THERAPY
ADVANCED NSCLC. STAGE III
Mediastinal LN involvement
Supraclavicularor scalene LN
Primary tumor invades local structures (heart, spine,greatvessels, etc)
STAGE III TREATMENT OPTIONS
Surgery if possible, sometimes neo-adjuvant chemotherapy is an option
Chemo/Radiation vs sequential chemotherapy and radiation
Drugs typically given with concurrent radiation are Taxol/Carboplatin (weekly) or Carboplatin/Etoposide.
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ADVANCED NSCLC. STAGE IV
M1a Pleural or pericardial effusion Tumor with pleural nodulesNodule in the contralateral lung
M1b Cancer spread outside of the chest
Chemotherapy vs. Supportive Care
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TREATMENT PARADIGMS AFTER 2004 Determination of histology at diagnosis is mandatory.
There are differences in survival between platinum based doublets.
Three drugs may be better than two, in specific populations.
Maintenance therapy is a novel strategy and an option.
Targeted therapies have become the first line standard of care for driving mutations
Immunotherapy has become a very important treatment option
P=0.03 P=0.05
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Targeted Agents
TARGETED THERAPIES
Targeting Vascular Endothelial Growth Factor(VEGF)Bevacizumab- first line (non-squamous only), Carbo/TaxolRamicirumab- second line (all histologies), docetaxel
Targeting Epidermal Growth Factor Receptor (EGFR) Monoclonal antibody against EGFR Tyrosine kinase inhibitors (erlotinib, afatinib),
osirmertinib for 2nd line (T790m mutation)
Targeting Anaplastic Lymphoma Kinase (ALK) crizotinib
ANGIOGENESIS
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PHASE III TRIAL IN NON-SQUAMOUSNSCLC: ECOG 4599 (N=855)
EligibilityNo previous chemotherapy
Non-squamous cellNo hx of hemoptysisNo CNS metastases
CPPaclitaxel 200 mg/m2
Carboplatin AUC 6(Q3 weeks) x 6 cycles
CPBCP x 6 cycles
+Bevacizumab (15 mg/kg)
Q3 weeks to DP
No crossover tobevacizumab
Stratification Variables:RT vs. no RTStage IIIB or IV vs. recurrentWt loss <5 % vs. > 5%Measurable vs. non-measurable
Sandler, et al. NEJM 355:2542-2550, 2006
Sandler, et al. NEJM 355:2542-2550, 2006
2-year survival 23 vs. 15%
HR=0.80
BEVACIZUMAB
RAMICIRUMAB
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ONCOGENE ADDICTION
Some cancers may be driven by a single mutation, without which the cancer cells dies.
Lung Cancer Mutation Consortium
INCIDENCE OF SINGLE DRIVER MUTATIONS
Chemotherapy
vs.
Targeted Agent
For 1st Line Therapy
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IPASS STUDYGefitinib vs. Carbo/Taxol in First Line Therapy in Asian Patients
Mok, ESMO 2008
Advanced NSCLCNo prior therapy
Never or light ex-smokersN+ 1217
Carbo-Taxol IVEvery 3 weeks
Iressa 250 mg/day
RANDOMI
ZATI
ON
Primary EndpointPFS
Secondary:ORROSQOLSafetyDisease-related symptoms
TYROSINE KINASES AND TKI’S
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CLINICAL RESPONSESAND RESISTANCE
ALK INHIBITOR: CRIZOTINIB
~250 kb ~300 kb
t(2;5) ALK genebreakpoint region
2p23 regionTelomere Centromere
3’ 5’
FISH ASSAY FORALK REARRANGEMENT*
Break-apart FISH assay for ALK-fusion genes1
ALK 29.3
EML4 42.3
ALK break-apart FISH assay[Courtesy John Iafrate, Massachusetts General Hospital]
1Shaw AT et al. J Clin Oncol 2009;27:4247–4253
1Shaw AT et al. J Clin Oncol 2009;27:4247–4253
q36.1
q36.3q37.2
q34
q32.1
q32.3
q33.2
q31.3
q24.3
q24.1
q23.2q22.2q22.1
q21.2q14.3
q14.1
q12.3q12.1
p12
p13.2p14
p16.1
p16.3
p22.1
p23.2
p22.3
p24.1
p24.3
p25.2
q36.1
q36.3q37.2
q34
q32.1
q32.3
q33.2
q31.3
q24.3
q24.1
q23.2q22.2q22.1
q21.2q14.3
q14.1
q12.3q12.1
p12
p13.2p14
p16.1
p16.3
p22.1
p23.2
p22.3
p24.1
p24.3
p25.2
Split signalNon-split signal
*Assay is positive if rearrangements can be detected in ≥15% of cellsFISH = fluorescence in situ hybridization
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TARGETS UNDER DEVELOPMENT
KRAS mutation ROS1 fusion: sensitive to crizotinib RET fusion PI3K/mTOR pathway MET: overexpression vs mutation:
Crizotinib, met antibodies
IMMUNOTHERAPY/CHECKPOINT INHIBITORS
IMMUNE CHECKPOINT INHIBITION
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PDL1 STAINING
IMMUNOTHERAPIES IN NSCLC
Opdivo (nivolumab) approved for 2nd line treatment in squamous cell NSCLC March 2015
Keytruda (pembrolizumab) approved for 2nd line treatment in PDL1 positive (any histology) patients Oct 2, 2015
Opdivo (nivolumab) expanded for use in any histology NSCLC Oct 9, 2015
Tencentriq (atezolizumab) PDL1 inhibitor approved for 2nd
line NSCLC in October 2016 Ketyruda (pembrolizumab) approved for 1st line NSCLC in
patients who are PDL1 high (>50%) in October 2016 Many immunotherapy combinations are currently being
studied.
CHECKPOINT INHIBITOR SIDE EFFECTS
Immune-related side effects, very different than chemotherapy
Most common side effects are fatigue, thyroid dysfunction, and rash.
Other side effects include pneumonitis, colitis, pancreatitis, hepatitis, adrenalitis, hypophysitis, type 1 diabetes
Treatment may include withholding treatment and administration of steroids
Side effects can quickly become life threatening
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PNEUMONITIS
STAGE IV TREATMENT SUMMARY: 1ST LINE
- Targeted therapy if applicable (EGFR, ALK, ROS1) Examples: erlotinib, afatinib, crizotinib
- -Chemotherapy - Pembrolizumab for PDL1-high patients
STAGE IV SUMMARY- SECOND LINE AND BEYOND
-Newer generation targeted therapies osimertinib, alectinib
PD1 inhibitors Second-line chemotherapy Clinical trials Targeted therapies (including clinical trials) can
be guided by genomic testing of either tumor specimen or circulating tumor cells
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CHEMOTHERAPY REGIMENS
Alimta (pemetrexed) + Carboplatin or Cistplatin Non-squamous histology
Gemzar (gemcitabine) + platinum Taxotere (docetaxel) + platinum +/-ramicirumab Taxol (paclitaxel) + platinum +/- bevacizumab
(adenocarcinoma only) Etoposide + platinum Gemcitabine + vinorelbine
NURSING IMPLICATIONS
Diagnosis (supportive care, emotional support) Treatment decision making (education) Surgery Radiation Chemotherapy Follow-up
CASE STUDY
64 year-old female, who has never smoked presents to her dermatologist for an enlarging skin nodule on her scalp. A biopsy is taken and consistent with adenocarcinoma- lung primary.
Further imaging shows multiple right lung nodules, enlarged right paratracheal and subcarinal lymph nodes
MRI of the brain is negative Molecular studies: EGFR, ALK, KRAS negative PDL1 testing = 80%
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QUESTIONS
What is her Stage? What is first line therapy for her? What are some nursing considerations for a
patient like this What is an appropriate second line therapy
CASE STUDY
75 year-old male with metastatic squamouscell carcinoma who has been on pembrolizumab for 4 months, with a good response to treatment. His labowork has been normal.
He comes to clinic for treatment and his LFTsare mildly elevated- AST 80, ALT 104, Alk Phos180, normal bilirubin
QUESTIONS
Is this cause for concern? Why or why not? What, if any, actions need to be taken? Should treatment be withheld?
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THANK YOU FOR YOUR ATTENTION!