-
predicts EGFR TKI sensitivity (erlotinib)
EGFR exon 19 deletion/exon 21 L858R mutation
-
poor survival and predictive of lack of benefit from platinum/vinorelbine chemotherapy or EGFR TKI thereapy
K-ras mutations
-
a very big risk after lung cancer
development of a secondary malignancy
-
rapidly growing cells with scant cytoplasm
typically in central airways
association with paraneoplastic syndromes
strong dose response association with cigarettel smoking
Small cell carcinoma
-
arise in proximal segmental bronchi and present clinically in lung periphery
tend to be slow growing
strong dose response relation to tobacco exposure
comprised of sheets of epithelial cells that frequently include keratin
can be associated with a parathyroid hormone like factor -- hypercalcemia
squamous cell
-
types of non-squamos, non small cell carcinoma
- adenocarcinoma
- bronchioalveolar
- large cells
- others
-
most frequent in US and in nonsmokers
mostly in our area
adenocarcinoma
-
relatively uncommon
found among nonsmoking females of asian descent that harbor unique EGFR mutations
responds to erlotinib
bronchioalveolar carcinoma -- subtype of adenocarcinoma
-
peripheral tumors and lack definite evidence of squamous or glandular maturation
large cell
-
indicated by pleural or chest wall pain, cough, restrictive dyspenea
Peripheral primary tumor growth
-
indicated by dysphagia, nerve paralysis syndromes, SVC, pericardial tamponade, pleural effusion, paraneoplastic syndromes
regional or metastatic tumor growth
-
stage of localized advanced disease
stage III
-
advanced disease
stage IV
-
disease that is confined to ipsilateral hemithorax and can be encompassed by a single radiation port
it is no necessary to radiate the whole lung area
limited stage small cell carcinoma
-
all other disease, including metastatic sites, pleural or cardiac effusion
can spread quickly
most people have it before they discover disease
extensive disease small cell carcinoma
-
improves delivery of external beeam radiotherapy and reduce toxicity
3D-CRT, IMRT
-
Adverse effects of radiation therapy
- acute effects start 2nd or 3rd week
- esophagitis, fatigue, nausea, pneumonitis, blood counts, superficial infections
-
adverse effects: follicular rash, diarrhea, interstitial lung disease, conjuctivitis, keratitis, corneal ulcerations
avoid concomitant 3A4 inducers
potential increased risk of bleeding with warfarin and NSAIDS
erlotinib and gefitinib
-
adverse effects: follicular rash, diarrhea, hypomagnesia, hypersensitivity rxns, and interstitial lung disease
cetuximab
-
criteria for cetuximab
- EGFR positive disease, ECOG perfomance status 0-2, no known brain metastases, no prior chemo o ranti EGFR therapy
- no k-ras
-
folic acid needed
premetrexed
-
4 major treatment modalities
- surgery
- radiation therapy
- EGFR inhibitors
- Cytotoxic Agents
-
For Non-small Cell Carcinomas resectable disease:
Tx of choice for stage I and II
Size of primary tumor adn extent of lymph node involvment is important
surgery
-
chemo recommended as adjuvant therapy for Non-small Cell Carcinomas resectable disease
- cisplatin based and XRT at discretion of investigator
- paclitaxel/carboplatin only recommended if patients cannot tolerate cisplatin
-
For Non-small Cell Carcinomas, postoperative __________ reduces local recurrences, increases toxicity, but controversial whether it improves OS
adjuvant radiation therapy
-
Tx options for Non-small Cell Carcinomas that is locally advanced
- surgery
- neoadjuvant -- radiation, chemo
- adjuvant -- radiation, chemo
-
when in radiation used for Non-small Cell Carcinomas with locally advanced disease as neoadjuvant therapy?
with those who are not candidates for chemotherapy
-
chemo for Non-small Cell Carcinomas with locally advanced disease as neoadjuvant therapy
preoperative chemo and radiation recommended for patients with resectable tumors
generally involves cisplatin and a second drug(etoposide, vinorelbine, vinblastine) or paclitaxel plus carboplatin
-
radiation as adjuvant therapy for Non-small Cell Carcinomas with locally advanced disease?
if surgical margins positive for tumor cells
may improve control for patients who have been completely resected
-
chemo for Non-small Cell Carcinomas locally advanced as adjuvant therapy?
may reduce distant recurrence in those that have been completely resected
administered to those who did not recieve preoperative radiation, or in pts with positive tumor margins
-
tx options for Non-small Cell Carcinomas with advanced, unresectable, or metastatic disease
- surgery
- radiation -- palliation
- controll of obstructed airways
- concurrent chemo
- EGFR inhibitors
-
concurrent chemo for Non-small Cell Carcinomas that are advanced, unresectable, or metastatic
platinum based chemo plus XRT provides a modest survival advantage
-
chemo for Non-small Cell Carcinomas that are advanced, unresectable, or metastatic
- overall: platinum based 2 drug chemo
- chemo provides modest sruvival advantage and is cost effective
-
indicated for tx of pts with locally advanced or metastatic NSCLC after failure of at least one prior chemo regimen
data suggests it is limited to people harboring specific EGFR activating mutations and absence of K-ras mutations
Erlotinib
-
For NSCLC _______ showed improved OS vs vinorelbine an cisplatin +/- cetuximab, but increase in grade 3 or 4 neutropenia and grade 2 follicular rash
Cetuximab
-
associated with best survival outcomes for metastatic NSCLC
platinum based combnation regimens
-
1st line therapy for chemo for Non-small Cell Carcinomas that are advanced, unresectable, or metastatic with a perfomance status of 0-1
- - chemo + bevacizumab: if non squamous cell NSCLC, no untreated CNS metastases, and no history of hemoptysis
- - cisplatin plus pemetrexed if non-squamous cell histology
- - cetuximab/vinorelbine/cisplatin if meets criteria for cetuximab
-
1st line therapy for chemo for Non-small Cell Carcinomas that are
advanced, unresectable, or metastatic with a perfomance status of 0-2
cetuximab/vinorelbine/cisplatin if meets criteria for cetuximab
-
what are the requirement for cetuximab?
- EGFR positive disease
- performance status of 0-2
- no know brain metastases
- no prior chemo or anti-EGFR therapy
-
for what NSCLC patients is maintenance therapy an option?
those who have recieved 4-6 cycles of chemo with stable non-progressive disease
-
2nd line and subsequent therapy for chemo for Non-small Cell Carcinomas that are
advanced, unresectable, or metastatic
- docetaxel: PS 0-2
- pemetrexed: PS 0-2
- erlotinib: PS 0-3
-
Median survival with extensive disease without tx is about 5 weeks
Dissemination of disease almost always has occured by diagnosis
Brain metastasis common
Small Cell Carcinoma
-
Tumor regression occurs in approximately 90% witih newly diagnosed SCLC
Adds to survival benefit in limited stage disease
Radiation therapy
-
SCLC is very sensitive to _______ _________. Can cure a small fraction of patients with _____ ______ disease
- Combination chemo
- Limited stage disease
-
1st line therapy of SCLC
- Limited stage: chemo (x 4 cycles) plus chest radiotherapy
- Exstensive stage: chemo
-
preferred with cuncurrent radiation therapy in limited stage SCLC
EP (cisplatin + etoposide)
-
For SCLC, alternating non-cross resistant regimens is not ______ ______.
______ _______ may be acceptable for patients at increased risk for toxicity but do not yeild comparable results. Original regimen can be used if relapse is > than __ _______
- proven superior
- single agents
- 6 months
-
duration of tx of SCLC is limited to about ___ ______
6 months
-
For all lung cancer, _____ _________ can be used for brain metastases, SCLC, symptomatic local or weight bearing bone lesions, and hemoptysis
radiation therapy
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