Lung Cancer

Question 1

1. Describe the epidemiology of lung cancer, including incidence and prevalence.

Answer 1

worldwide it is the most common cancer, the incidence has steadily been increasing in all populations since the 1930s, rate of increase faster than any other cancer

Question 2

2. Be aware of temporal trends in lung cancer.

Answer 2

rates have begun to decline in men, but rates in women is only starting to plateau, Af-am men continue to see an increase.

Question 3

3. Contrast the epidemiology of lung cancer between genders.

Answer 3

incidence men to women is 1.7:1 which has changed from 4:1 ratio of the ’60s demonstrative of increasing tobacco use by women

Question 4

4. Identify the mortality trends of lung cancer.

Answer 4

lung cancer is the number one cancer killer in both men and women in the US; statistics related to cancer mortality in the US and world are largely driven by lung cancer mortality

Question 5

5. Recognize tobacco smoking is a risk factor for lung cancer.

Answer 5

cigarette smoking is the predominant cause of lung cancer (85-90% of lung caners)

vapor contains initiators, but no promoters where as the particulate phase contains both initiators and promotors

compared to non-smokers, average smokers <1pk/d have a 10 fold increase in risk, heavy smokers 2ppd have a 20 fold increase

Question 6

6. Define the relationship between asbestos and lung carcinoma.

Answer 6

non-smoking asbestos workers have a 5 fold increase in risk for lung cancer, those who smoke have a 50-90 fold increase in risk

other chemical carcinogens include nickel, chromates, mustard gas, arsenic, beryllium, halo ethers

Question 7

7. Recognize the relationship between radiation and lung carcinoma.

Answer 7

radon exposure increase risk for lung cancer (a mean level of 1.5 pCi/L in US home contributes to 0.3% lifetime risk for lung cancer)
it is the second cause behind tobacco exposure

Question 8

8. Identify how air pollution can contribute to lung carcinomas.

Answer 8

there is a slight urban preponderance, that maybe attributable to air polluion

Question 9

9. Define genetic predispositions associated with lung carcinoma.

Answer 9

genetic predisposition is not well defined, some studies have suggested that first degree relatives of lung cancer pro bands have an increased risk for developing lung cancer

Question 10

10. Explain the pathogenesis of tumor suppressor genes in lung carcinomas.

Answer 10

tumor suppressor genes are associated with lung cancer; frequency and type of mutations differ considerably between small SCLC and non-small cell lung cancer

Rb mutations are found in >95% of SCLC but in only a minority of NSCLC
p53 mutations are found in >90% of SCLC and >50% of NSCLC

Question 11

11. Describe the molecular biology of oncogenes in lung cancer.

Answer 11

K-ras mutation is more frequently found in smokers, those with adenocarcinoma and those with poorly differentiated tumors, but usually not present in SCLC

EGFR are other possible targets for therapy

Question 12

12. Define pathogenesis of lung cancer.

Answer 12

injury of bronchial mucosa causes squamous metaplasia to carcinoma and the genetic alterations increase

current hypothesis proposes chronic injury and genetic factors initiating a cascade of metaplasia and atypic mediated by growth factors

Question 13

13. Assess how dysfunctional cell kinetics can lead lung carcinoma.

Answer 13

average volume doubling time is 33 days for SCLC and 100 for large cell and squamous

proliferative index is 5% and the proliferative index can reach 25% or more in some small cell lung cancers

potential cell doubling time ranges from 4-12 days (estimate of the average cells speed in proliferation

not: short potential doubling time but long volume doubling time is explained by a high cell loss factor

Question 14

14. Illustrate anatomic and histologic properties of various types of lung cancer.

Answer 14

anatomic correlates: ¾ cancers arise near major bronchi, minority arise in the periphery and are usually adenocarcinoma or large cell

squamous cell carcinoma and small cell carcinoma typically arise in the central chest, close to or within the large and intermediate bronchi around the hill

histologic correlates: 6 types of epithelial cells: ciliated, brush, mucus-secreting goblet (adenocarcinoma), Kulchitsky (small cell carcinoma) and two types of small multi potential cells (metaplatic squamous epithelium)

Question 15

15. Describe the histologic classification of the various types of lung cancer.

Answer 15

4 common types:
small cell carcinoma 20-25%
squamous cell carcinoma 25-40%
adenocarcinoma 25-40%
large cell carcinoma 10-15%

(anything that is not small cell carcinoma is labeled “non-small cell lung cancer” and there can be mixed subtypes)

Question 16

16. Be aware of emerging trends in the histologic classification of lung cancer.

Answer 16

proportion of adenocarcinoma may have exceeded that of squamous cell carcinoma (females present with adenocarcinoma) and new more deeply inspired cigs are exposing peripheral lung (adenocarcinomas)

most lung cancers in non-smokers are adenocarcinomas

Question 17

17. Summarize typical symptoms and clinical presentation of lung carcinoma.

Answer 17

cough, hemoptysis, shortness of breath and chest pains

regional growth can cause hoarseness, plexopathy, effusion, pain, SOB, lung collapse, SVC syndrome (venous congestion of the head and arms- jugular distention)

metastases

Pancaost’s tumor (cancer in the apex with extension into the chest wall pleura and brachial plexus) includes a triad of symptoms: 1. Horner’s syndrome, 2. shoulder pain 3. pain and muscle wasting of the the distribution inferior brachial plexus (ulnar and interosseus)

Question 18

18. Illustrate radiologic findings present in lung carcinoma.

Answer 18

pulmonary nodule is detected as abnormal, especially an increase in size over time

Question 19

19. Describe the utility of various radiologic studies (PET, CT, bone scan, etc.) instating lung cancer.

Answer 19

definitive tissue diagnosis is key because tx. for small cell versus non small cell is different

central lesions tissue is collected with fiberoptic bronchoscopy, peripheral lesions use radiographilcally- guided percutaneous biopsy

PET: highly metabolically active tumor takes up glucose and it is the most accurate method of staging lung cancer patients

CT scans of the chest and abdomen (looking of liver and adrenal metastases (good anatomic definition and precise measurement)

CXR and bone scan, brain MRI not reliably imaged by PET or standard CT

Question 20

20 Contrast the staging for non-small cell lung cancer with that of small cell cancer.

Answer 20

TNM system is used for non-small cell lung cancer

small cell cancer, tumor within one hemithorax is reffered to as limited stage whereas tumor beyond this is referred to as extensive (TNM system not commonly used)

Question 21

21. Recognize the indications and contraindications to surgery to non-small cell lung cancer.

Answer 21

surgical resection is the treatment of choice if technically and medically possible (almost all stage I and II) best with limited pulmonary comorbidity and no mediastinal lymph involvement

contraindications: extrathroacic distant metastases, superior vena cava syndrome, vocal chord paralysis, malignant pleural effusion, cardiac tamponade, main stem pulmonary artery involvement, metals to the contralateral lung or mediastinal nodes, bilateral endobronchial tumors

Question 22

22. Cite general treatment regimens for small cell lung cancer.

Answer 22

majority of limited stage patients have micrometastitc disease at diagnosis, tx, with aggressive chemoradiotherapy with curative intent although recurrece is common

prophylactic cranial irradiation involves irradiating the brain int eh absence of proven metastases

extensive stage: all patients with extrathroracic extension, principal treatment is chemotherapy, however recurrence is the general rule (which must be treated with new class of drug)

Question 23

23. Describe the prognosis of lung carcinoma.

Answer 23

patients with higher stage disease have a predictably lower probability of surviving disease

overall 5 year survival rate is 5-15%, for small cell lung cancer, the 5 year survival has ben less than 5%

Question 24

Why is mortality so high with the majority of lung cancers?

Answer 24

majority of lung caner patients (both SCLC and NSCLC) recur after therapy and die from their disease, and the number one reason for this is the lack of an effective systemic therapy; chemotherapy almost always fails to provide durable control of the disease

Question 25

21. Cite general treatment regimens for non-small lung cancer according to stage.

Answer 25

Stage I solitary and resectable lung nodule without spread is removed with adjuvent chemo if larger than 4cm

Stage II larger more extensive primary tumor, or metastases to hilar lymph nodes, chemotherapy post surgery often used

Stage IIIA patients with ipsilateral mediastinal lymph node involvement which can be microscopic or bulky and surgery and radiation are debated

Stage IIIB extensive primary tumors or with contralateral mediastinal nodal involvement, treated with combo chemo and radiotherapy, post op tx. remains controversial

Stage IV: patients with extra thoracic metastatic disease, these patients are not curable and are treated with palliative intent, patents likely to benefit most form aggressive palliative therapy are those with the best performance status

Question 26

Describe some of the latest small molecule treatments that target lung cancer.

Answer 26

EGFR inhibitors such as erlotinib show efficacy in certain non-smokers with EGFR over expression

bevacizumab: antigeniogenic agent used in first-line therapy and part of maintenance strategy