Lung Cancer
*HYA* *Paraneoplastic syndromes (PNPS) * NSCLC (1) What is the only paraneoplastic syndrom that is common in NSCLC? (2) What paraneoplastic syndrome is common in Squamous Cell CA? (3) Clubbing of the fingers and toes? - which *NSCLC*? *(summary of the PNPS on slide)*
(1) *Cancer Cachexia* -general state of ill health involving *marked weight loss and muscle loss*- this results in depression as well (2) *Hypercalcemia* - ectopic production of *PTHrp* - acts on bones to stimulate osteoclasts (bone resorption) & promotes PO4 wasting via kidneys - *stones, bones, groans, psychotic overtones* (abdomen / bone pain and confusion) (3) Hypertrophic pulmonary osteoarthropathy (HPO) - more common in adeno & large cell CA than SCC
*HYA:* 3 common paraneoplastic syndromes (PNPS) in *SCLC* *(summary of the PNPS on slide)*
(1) *Syndrome of inappropriate antidiuretic hormone (SIADH)* - hyponatremia (confusion) (2) *Lambert-Eaton myasthenic syndrome (LEMS):* - igG against presynaptic Ca2+ channels reduces the release of ACh release (despite normal ACh vesicles, normal presynaptic conc, and normal post-synaptic recpetors) (3) *Cushing's syndrome: Ectopic ACTH production* - ↑ ACTH → ↑ cortisol = progressive obesity / hyperglycemia / osteoporsis
(1) What is more sensitive for lung screening? (2) What imaging lead to *high rates of false-positives*? (3) What are the indications for a low dose CT chest image? *- Review size of nodule- *
(1) *low-dose computerized tomography (LDCT) is Significantly more sensitive than chest radiograph* for identifying small asymptomatic lung cancers (2) CXR & LDCT (3) any smoker or former smoker with 30+ pack year history, aged 55-77 years.
(1) How can a tumor's metabolic activity be measured using the standardized uptake value (SUV) ? (2) Why is a *tissue diagnosis* necessary? *HYA* (3) What can be used to diagnose with central tumors? (4) Percutaneous transthoracic *FNA (fine needle aspiration)* of pulmonary nodules can be useful in some clinical settings (usually performed under fluoroscopic or CT guidance). What occurs if you have negative results with FNA? *HYA* (5) How would one screen for mediastinal LN?
(1) PET-CT scan - uptake is flurodeoxyglucose (FDG) (2) *Tissue Diagnosis:* -determines NSCLC or SCLC - r/o nonmalignant process - r/o lung mets from primary tumor @ another site (*Info is crucial for Tx planning*) (3) *Central Tumors* - sputum cytology - flexible fiberoptic bronchoscopy (4) negative results on FNA must be considered interdeterminate (NOT negative) until the diagnosis is est. by another method (5) Mediastnoscopy or *endobronchial ultrasound (EBUS)*
(1) How does one treat Small Cell Lung Cancer? (2) What should you always image if you believe someone has SCLC? - besides the chest- *-Review limited stage (LS) SCLC-*
(1) SCLC is Highly responsive to chemotherapy and radiotherapy - usually relapses within 2 yrs despite treatment (2) Brain *NOTES:* - SCLC is a disseminated disease in most patients at presentation and is very responsive to chemotherapy. Thus systemic chemotherapy is an integral part of the initial treatment. -Most patients with LS-*SCLC will have clinical or pathologic evidence of mediastinal lymph node disease*. - Careful staging, including *invasive staging of the mediastinum and MRI of the brain*, is indicated to identify the small fraction of patients with LC-SCLC who do not have mediastinal or metastatic disease.
Most common type of lung NSCLC in *never smokers?* *2011: New classification system:* (1) *Preinvasive:* - atypical adenamtous hyperplasia (atypical ____ = Clara cells) - _______ ; lesions < 3 cm and without invasive characteristics (2) *Minimally invasive:* - lesions 3 cm or smaller and are predominantly ______ pattern, invasion <5mm at most (3) *Invasive:* - __ % of all cases of adenocarcinoma-Lepidic, Acinar, papillary, micropapillary, or solid with mucin production
*Adenocarcinoma* (in general most common histologic subtype of lung cancer) - more likely to have *distant mets* than squamous cell CA *2011: New classification system:* (1) *Preinvasive:* - type II pneumocytes, adenocarcinoma in-stiu (2) *Minimally invasive* - lepidic pattern (3) *Invasive:* - 90%
In *adenocarcinoma* what type of mutations are seen in never smokers and what type in smokers? Squamous Cell carcinoma occur do to the amplification of what gene? Is Adenocarcinoma or Squamous Cell Carcinoma recommended for routine screening after being diagnosed?
*Adenocarcinomas:* *Never smokers:* (*tyrosine kinases*) - EGFR ( 40% of adenocarcinomas in Asians), ALK (*gene rearrangments*) *Smokers:* - KRAS Squamous Cell Carcinoma: - fibroblast growth factor receptor (FGFR) *NOTES:* -It is noteworthy that EGFR and KRAS mutations and ALK gene rearrangements are usually mutually exclusive.
What are the sites of metastasis from lung cancer? Review slide of the symptoms included with each organ (esp. know the bolded)
*METS sites:* - *adrenal > 50%* (*asymptomatic*) - liver 30-50% - *brain* 20% - bone 20% Remember these are all *M1* because they are traveling from the lungs!
How does one treat Extensive SCLC?
*NOTES:* OVERVIEW :THE WHOLE PATIENT Treatment of lung cancer, whether with surgery, chemotherapy, radiation therapy or a combination of these, can be associated with *substantial toxicity*. (do least amount of harm) Patients with significant impairment due to their lung cancer or comorbid conditions may not be able to withstand resection or alternatively aggressive chemoradiotherapy. Performance status can be assessed by a variety of methods including the *Karnofsky Performance Status (KPS) and the Eastern Cooperative Oncology Group Performance Scale (ECOG PS).*
Review the Flow Chart of *Dx of NSCLC*:
*NOTES:* -Only a minority of patients with non-small cell lung cancer (NSCLC) have pathologic stage I and II disease when diagnosed = aggressive therapy -Surgery is the standard treatment for medically operable patients with clinical stage I and II NSCLC, in whom there is no evidence of mediastinal involvement prior to surgical resection.
What does Adenocarcinoma -in-stiu look like? *-preinvasive-*
*NOTES:* -adenocarcinoma in situ is composed of *well-differentiated columnar cells* (see arrow above) that proliferate along the framework of alveolar septa, a so-called lepidic growth pattern.
What are the different types of NSCLC? - 80-85% of cancer *Neuroendocrine* derived cancer are what?
*NSCLC:* (1) Adenocarcinoma - *peripheral* , smokers / non-smokers - multiple variants - 40% (2) Squamous cell carcinoma - *central*, smokers (3) Large cell Carcinoma - *peripheral*, (prior) smokers *Neuroendocrine:* - Small cell lung cancer (SCLC) - Large cell neuroendocrine (LCNE) - Carcinoid
Are these* Gene Function Lost:* found in NSCLC or SCLC? *P53* *Rb* *LKB1* *Genes on short arm chromosome 3 (3p)*
*P53* - *NSCLC & SCLC* (correlated w/ cig smoking) *Rb* - not expressed in 90% of *SCLC* *LKB1* - NSCLC Genes on short arm chromosome 3 (3p) - 50% SCLC & 90% NSCLC
Highest frequency of Squamous cell carcinoma is what? What does the histology show? - highlighted on slide-
*TP53 mutations* (also seen in Li-Fraumeni syndrome) *NOTES:* Classifications: (1) Pre-invasive -Squamous dysplasia -Squamous cell carcinoma-in-situ (2) Invasive
*HYA:* *Solitary Pulmonary Nodule (SPN):* What must the size be of the SPN that is identified on CT scan? Descirbe the different paths that can be taken? (chart) - Benign on CT scan? - Compare to old CXR or CT scan? - No old CXR or CT scan?
- *SPN 8-30mm* identified on radiograph *NOTES:* -CT = computed tomography; FNA = fine-needle aspiration; PET = positron emission tomography
Horner syndrome? *Hint from First Aid:* Pam is Horny
- ptosis - anhidrosis - misosis caused by extension of the tumor into the paravertebral sympathetic nerves
*Pancoast syndrome:* characterized by _____ in an ulnar distribution, is caused by tumor invasion of _____ in the superior sulcus.
- shoulder pain radiating to the arm - C8 and T1
*Lung Cancer Stats:* Average age at diagnosis of lung cancer is what? Highest incidence seen in what race? Most common risk factor? - what contributes to a 4 fold increase to lung Ca with smoking? How does one find pack years? What is and is not a risk factor for mesothelioma?
70 yoa (2 out of 3 ppl dx with Lung Ca are 65 yrs or older) African American males RF = cigarette smoking (est. responsible for 85-90% of lung cancer) -4 fold increase asbestos Pack years = # of packs per day x # of yrs smoked (pts w/ 20-30 pack yrs increased risk of lung Ca) RF for mesothelioma is asbestos NOT smoking
When do you stop treating lung cancer aggressively? What do patients have that are staged as a *pathologic STAGE III*? The difference between *Clinical stage & Pathologic stage* is staging before surgery & biopsy is done. (clinical = before, pathologic = after)
Based on anything below Red line so after *Stage IIB* Patients with mediastinal lymph involvement *NOTES:* -Only a minority of patients with non-small cell lung cancer (NSCLC) have *pathologic stage I and II disease when diagnosed. In contrast to locally advanced (stage III) and disseminated (stage IV) disease, early stage disease is frequently curable with aggressive therapy*. - *Pathologic staging of the mediastinum* is required prior to definitive treatment for clinical stage I and II disease, either as a separate procedure or as the initial step in a planned surgical resection. *Patients with mediastinal lymph involvement are restaged as pathologic stage III and are treated accordingly*.
How can one manage pain in cancer patients? *- ask cancer patients about their pain regularly- *
Can treat pain with *ASA NSAIDs, & Acetaminophen* if it is on a *schedule* - start as early as possible before the pain sets in *NOTES:* - review other considerations
___ modifications involving *changes in DNA methylation* are common in lung cancer; include hypomethylation, dysregulation of DNA methyltransferase I, and hypermethylation.
Epigenetics *NOTES:* - Epigenetics refers to a change in gene expression that is heritable but does not involve a change in DNA sequence. -
What nerves passes through the aortico-pulmonary window (susceptible to injury secondary to mediastinal lymph node involvement)? - Injury causes what? Tumor invasion of the mediastinum can cause paralysis of the ____ which in turn can cause *elevation of the hemidiaphragm*. - remember can do the *sniff test*
Left recurrent laryngeal nerve - Injury results in vocal cord paralysis + subsequent hoarseness. phrenic nerve
What are the different variants of adenocarcinomas? -*LAPS*
Lepidic, Acinar, Papillary, Solid
Does smoking cessation reduce risk to that of a never smoker? What fraction of smokers develop bronchial malignancy? What else can cause bronchial malignancy?
NO, it will gradually reduce the risk for the development of lung cancer but never to that of a non-smoker. 11-15% of heavy smokers 2nd hand smoke, Radon, asbestos, ionizing radiation (imaging) - Lung CA susceptibility probably has genetic basis- *NOTES:* - coach your smoking pts to quit; quitting even after dx of lung CA can be beneficial to pts (smoking alters the metabolism of chemotherpay drugs) - avg dose of millirems (mrems- 1/1000 of a rem) per person per year is *620*- jet plan has as little as 0.5 mrem per hour in air and CT scans has 800 mrem-
What type of cancer can occur in *never-smokers*? What are the genetic alterations? Is there criteria to select patients for more intense screening program ?
NSCLC occur in never-smokers (10-15%) *EGFR & ALK* - incidence increases with age, no clear change in risk has occurred over time, no clear gender bias exists. - *females higher risk in East Asian countries (CHINA)* NO
What are the 2 histologic groups of lung cancer?
Non-small cell lung cancer (NSCLC) - 80-85% and small cell lung cancer -10-15 % Most lung cancer originate from the bronchial epithelium & are termed carcinomas Less common (<5%) pulmonary neoplasms (not carcinomas) --i.e. *Carcinoid tumors*
*Treatment options of NSCLC:* Initial Treatment of *localized disease* is the (*the same or different*) for all 3? Based on the above answer what are the treatment(s)?
Same Tx: - *early stage disease* = *surgical resection* = best opportunity for cure -*More extensive intrathoracic disease* = *concurrent chemoradiotherapy* - Advanced disease: managed *palliatively with systemic therapy and/or local palliative modalities* (cannot cure)
*Lung Cancer Epidemiology:* (T/F) Lung cancer is the leading cause of cancer mortality* globally and in the U.S.*?
True:; #1 globally and US for mortality. Also #2 cancer incidence in U.S. (Prostate #1 men and Breast #1 women) *NOTES:* -The incidence and mortality related to lung cancer in men have declined during the last two decades in Western countries but continue to increase in the developing world. - *Most dramatic increases in lung cancer incidence & death globally are in CHINA* - *5 yr survival rate* is @ 17%;
Undifferentiated malignant epithelial tumor that lacks cytologic features of other forms of lung cancers? 1 histological variant is more like SCLC is + staining for what?
large cell carcinoma (high mitotic rate and necrosis) chromogranin A, synaptophysin *NOTES:* -Difficult to diagnose accurately due to abundance of *necrotic tissue and poor degree of differentiation* (need an adequate tissue specimen) - Expresses few or none of the markers of adenocarcinoma (TTF-1, napsin-A) or squamous cell carcinoma (p63)
What is *superior vena cava syndrome*?
swelling of the face and arm, superficial venous engorgement (caused by either a central tumor in the right lung or mediastinal lymphadenopathy)
T/F SCLC has been declining in the past 30 years? SCLC Pathology:
true; # of adults that smoke have decreased (smoking is strongly associated with SCLC; very rare in never smokers) SCLC Pathology: - high grade *neuroendocrine tumor* - high degree of *mitosis and abundance of necrosis* - need immunostaining for *TTF-1, chromogranin A, synaptophysin, &CD56*