Lecture 8: Lung Cancer

Lung Cancer

-the leading cause of cancer ___ in the US (15.6% 5-year survival)

-average age at diagnosis = 70 years

mortality

Lung Cancer Risk Factors

1. _____

2. radon, ionizing _____

3. ___

4. ___ exposure (rock miners, coal tars, petroleum, nickel, arsenic)

5. may be genetic predisposition

smoking, radiation, abestos, occupational

Smoking

-primary risk factors

-accounts for >85% of all lung cancer-related deaths

-risk for lung cancer goes exponentially up if patient exceeds ___ pack-year history

-risk decreases after smoking cessation, measurable difference after __ years

-80-90% reduction after __ years

-increased risk with second-hand smoke __-__ associated with living with a smoker

30, 5, 15, 20, 30

Lung Cancer Prevention

-no effective prevention at this time

-___ reduction/cessation decreases risk

smoking

Lung Cancer Screening

-low dose CT scans ONLY recommended for __ risk individuals

high

Lung Cancer Screening- High Risk Individuals

age ___-___ years of age

AND

≥___ pack-year smoking history

AND

currently smoking or quit

55-80, 20, 15

Lung Cancer Signs and Symptoms

-___ (most common symptom)

-___ (coughing up blood)

-____

-chest pain

-wheezing/stridor

-hoarseness

-pleural or pericardial effusion

-weight loss

cough, hemoptysis, dyspnea

Lung Cancer Sites of Metastasis

-___ ___

-___ (may result in liver dysfunction)

-___ (may result in neurologic defects)

-___ (may result in bone pain, fractures, and/or spinal cord compression)

-adrenal glands

lymph nodes, liver, brain, bone

Lung Cancer Diagnosis

-location of primary tumor

-evaluation of primary tumor (CXR, chest CT, PET scan)

-need to obtain tissue with __ or transthoracic needle ___

bronchoscopy, biospsy

2 types of Lung Cancer:

-__-___ ___ lung cancer (NSCLC)

-___ ___ lung cancer (SCLC)

non-small cell, small cell

NSCLC

-generally ___ growing

-low sensitivity to chemotherapy

-moderately sensitive to radiation

slow

NSCLC Types

1. _____ (most common, grew in "squishy"/visceral part of patients lungs, surgery is easier with this type)

adenocarcinoma

NSCLC Types

2. ____ ___ ___ (slower growing, clearly related to smoking, more favorable prognosis than adenocarcinoma, wraps around organs)

squamos cell carcinoma

NSCLC Types

3. ___ ___ ___

large cell carcinoma

TNM Staging System

T: tumor ___

N: degree of ___ ___

M: presence/absence of distant ___

size, nodule development, metastasis

NSCLC Stage I

-standard = ____ ___ (may be lung-sparing, lobectomy, pneumectomy, VATS)

-if not a surgical candidate, radiation can be used with curative intent

surgical resection

NSCLC Stage II

-standard = ____ ___

-if not a surgical candidate, radiation can be used with curative intent

-EVERYBODY with this stage should get ___ ___

-___ is a major concern

surgical resection, adjuvant chemotherapy, recurrence

NSCLC Stage II Adjuvant Chemotherapy Options

-platinum doublet: ____ + something else (paclitaxel)

cisplatin

NSCLC Stage IIIa

-controversial

-order of regimens under debate

-may use ____ chemo, ____, ____, and ___ chemo

neoadjuvant, radiation, surgery, adjuvant

NSCLC Stage IIIa Chemotherapy Options

-___-based chemotherapy (cisplatin) + "something else"

platinum

NSCLC Stage IIIb

-____ at the present time (cannot do surgery)

-___-based chemotherapy (cisplatin) + "something else"

-also use ____

-duration should not exceed __ cycles

unresectable, platinum, radiation, 8

NSCLC Stage IV

-___ (cannot do surgery)

-____

-goal is to improve QOL

unresectable, incurable

NSCLC Stage IV

-choice of chemo regimen depends on patient's ECOG ___ ___ (PS) and presence/absence of ___ ___

performance status, driver mutation

If tumor has ___ ___, we can use fancy targeted drugs and patient might not have to get chemo

driver mutations

ECOG Performace Status (PS)

___ = fully active (good!)

____ = ambulatory but restricted (good!)

___ = up and about more than 50% of waking hours (borderline)

___ = confined to bed more than 50% of waking hours (borderline)

____ = completely disabled (do not qualify for chemo)

____= dead

0, 1, 2, 3, 4, 5

NSCLC Stage IV- PS 0 or 1 - No driver Mutations

-platinum doublet (since this is palliative intent-we usually choose ___ because its gentler)

-___-___ cycles of platinum doublet is recommended, then take pictures of tumor

carboplatin, 4-6

NSCLC Stage IV- PS 2 or 3- No driver Mutations

-platinum agents are too toxic

-we use single ___-___ chemo agent (paclitaxel, doxetaxel, gemcitabine, vinorelbine, irinotecan, etoposide, vinblastine, pemetrexed)

-4-6 cycles recommended

non-platinum

Driver Mutations in NSCLC

If programmed death receptor ligands (PD, PDL) → use ___ ___ ___

immune checkpoint inhibitors

Driver Mutations in NSCLC

If mutated EGFR → use ___ ___ ___

anti-EGFR agent

Driver Mutations in NSCLC

If ALK, ROS1, others → use an agent ____ at specific ___

targeted, mutation

Pembrolizumab brand?

Keytruda

Pembrolizumab (Keytruda)

-immune checkpoint inhibitor antibody

-inhibits ___ receptor

-ultimately allows ___ cells to recognize tumor as foreign

PD-1, T

Pembrolizumab (Keytruda)

-can be used in 1st line setting if the tumor proportion score (TPS) ≥ ___%

1

Pembrolizumab (Keytruda)

If TPS 1-50% → Keytruda can be ___ with chemo

combined

Pembrolizumab (Keytruda)

If TPS ≥ 50% → Keytruda can be given as ___ agent, no chemo

single

Pembrolizumab (Keytruda)

-does not cause usual adverse effects of traditional chemo

-adverse effects = "-___" (autommine diseases, including colitis, pneumonitis, thyroiditis)

itis

EGFR Inhibitors

-__ ___ inhibitors that block epidermal growth factor receptor

tyrosine kinase

EGFR Inhibitors

-FDA approved as 1st line therapy alone or in combo with chemotherapy in patients with intracellular EGFR ___

mutation

Lung Cancer : can use EGFR inhibitor if intracellular EGFR is ___

Colon Cancer: can use EGFR inhibitor if extracellular EGFR is ____

mutated, unmutated

Different than colon cancer tx → the EGFR inhibitor we give for Lung Cancer is ____ (Tarceva)

erlotinib

EGFR Inhibitors in NSCLC

-dose = ____ daily

-best absorbed on __ stomach

-select toxicities include __ and diarrhea

-substrates of ___

PO, empty, rash, CYP3A4

If patients tumor has a driver mutation, there are many drugs they can use which are all ___

oral

Second Line Treatment for NSCLC Stage IV

-reassess ___ and patient goals

-is there a __ driver mutation?

-can use single agents we haven't tried before (nivolumab, EGFR inhibitor, other targeted agent, docetaxel, pemetrexed)

PS, new

Small Cell Lung Cancer (SCLC)

-___ proliferation

-highly ___ to radiation and chemotherapy

-___ disease at diagnosis (chemotherapy is mainstay, ___ has NO role)

-overall 5 year survival = 5%

rapid, sensitive, widespread, surgery

SCLC Staging

____ stage = confined to ipsilateral hemithorax, can be encompassed within one XRT field

____ stage = beyond ipsilateral hemithorax (distant metastases)

limited, extensive

Limited Stage SCLC

-goal of treatment = ___

-____-based regimens are standard first line therapy

-best data = cisplatin + etoposide + XRT

cure, platinum

Limited Stage SCLC

-____ + ___ ____ given at same time

-total of 4-6 cycles

-____ ____ ___ (PCI) should be considered for patients with complete response (we radiate their brain bc this cancer probs traveled there)

XRT, concurrent chemotherapy (platinum doublet), prophylactic cranial irradiation

Extensive Stage SCLC

-rarely curable

-we give ____-based chemo for 4-6 cycles (usually carboplatin because pallative intent)

-we rarely give radiation, only if used for ____ (eg if tumor is crushing windpipe or for brain metastasis)

-____ has no role

platinum, palliation, surgery

Chemotherapy: Extensive Stage

-______ + etoposide is preferred

-cisplatin + etoposide

-cisplatin + irinotecan

carboplatin

SCLC Recurrent Disease

-most patients will relapse or progress after initial treatment

-second line treatment provides ___

-second line treatment based on __ to relapse

-second line treatment is 1 single drug

palliation, time