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1. The incidence of invasive meningococcal disease in the US is highest in which group(s)?
Infants
Infants and the elderly
Adolescents
Infants and adolescents
2. Which serogroup of N. meningitidis is the major cause of vaccine-preventable endemic disease in Europe and North America?
A
B
C
Y
3. Which of the following statements about the changing epidemiology of meningococcal disease is most true?
The US prevalence of serogroup Y has increased dramatically in the past decade
Serogroup B is only a minor cause of disease in the United Kingdom
The first global outbreak of serogroup Y was in Hajj pilgrims
The prevalence of serogroup B disease is increasing in the US
4. True or false: The first global outbreak of serogroup W-135 began in Saudi Arabia during the 2000 Hajj pilgrimage, and later spread worldwide.
True
False
5. Which of the following is true of meningococcal immunization in infants?
The currently licensed ACYW vaccine is recommended for infants older than 6 months
All infants should be immunized against serogroup B meningococcal disease
An investigational ACYW conjugate vaccine has been shown to be immunogenic in infants
Maternal antibodies protect infants until the second year of life
6. What mechanism is thought to contribute to outbreaks in immunized populations?
Capsular switching and clonal expansion
Palindromic insertion elements
Viral–mediated transduction
Flagella antigen switching
7. Which of the following is a property of conjugate vaccines that is absent in polysaccharide vaccines?
Booster effect
Herd immunity
Reduced carriage
All of the above
8. According to the ACIP, routine immunization against meningococcal disease is recommended for which of the following groups?
Persons 2–55 years of age at increased risk
Persons travelling to endemic areas
College freshmen living in dormitories
All persons 11–18 years of age
All of the above
9. The CDC has estimated that immunizing all US 11-year-olds against meningococcal disease would result in which of the following?
Prevention of 359 cases
Prevention of 300 deaths
Twenty-five cases of GBS
All of the above
10. Which of the following is a component of an investigational vaccine against serogroup B that has been shown to be immunogenic in infants?
Factor H binding protein
Plasma membrane vesicles
Siderophores
Temperature-sensitive toxin

Answers:

The incidence of invasive meningococcal disease in the US is highest in which group(s)?
Answer: Infants and adolescents
Meningococcal disease has the highest incidence in infants. As protection conferred by maternal antibodies wanes, infants become vulnerable to invasive infection. An increase in incident meningococcal disease is also seen in adolescents, presumably because of the increased frequency of behavioral risk factors in this age group.
Which serogroup of N. meningitidis is the major cause of vaccine-preventable endemic disease in Europe and North America?
Answer: C
Although serogroup A is the leading cause of endemic meningococcal disease worldwide, it is rare in Europe and North America. Serogroup B is a common cause of illness in Europe and North America, but is not currently vaccine-preventable. Serogroup C is the most common cause of endemic meningococcal disease in Europe and North America. Widespread prevention with vaccine has been successful in Europe, Canada, and the US.
Which of the following statements about the changing epidemiology of meningococcal disease is most true?
Answer: The US prevalence of serogroup Y has increased dramatically in the past decade
Since the early 1990s, US surveillance has shown serogroup Y to be rare, accounting for about 2% of cases; in 2005, however, it accounted for nearly a quarter of all cases. Immunization in the United Kingdom has led to a dramatic decline in the incidence of serogroup C disease. As a result, serogroup B is now responsible for up to 90% of invasive disease. In contrast, prevalence of serogroup B disease in the US has remained around 45% since the late 1980s. In 2000, meningococcal disease caused by serogroup W-135 led to a worldwide series of outbreaks caused by infected Hajj pilgrims returning from Saudi Arabia.
True or false: The first global outbreak of serogroup W-135 began in Saudi Arabia during the 2000 Hajj pilgrimage, and later spread worldwide.
Answer: True
Although Saudi Arabia required participants in the 2000 Hajj to be immunized against serogroups A and C, the unexpected emergence of disease caused by W-135 led to an outbreak during the pilgrimage. With the return of travelers to their home countries, outbreaks erupted around the world. In Burkina Faso, there were over 13,000 cases and 1400 deaths. Licensed vaccines containing W-135 are now available and required for entry to Saudi Arabia for the Hajj.
Which of the following is true of meningococcal immunization in infants?
Answer: An investigational ACYW conjugate vaccine has been shown to be immunogenic in infants
Currently, ACYW is licensed for use in persons over 2 years of age, as this vaccine has not been shown to be immunogenic in infants younger than 2 years of age. A phase 2 study conducted in the United Kingdom and North America showed that a high proportion of infants immunized at 2, 4, and 6 months of age with an investigational ACYW-CRM vaccine produced functional antibody against homologous strains. Currently in the US, no vaccine against serogroup B is approved for immunization of infants.
What mechanism is thought to contribute to outbreaks in immunized populations?
Answer: Capsular switching and clonal expansion
N. meningitidis undergoes allelic replacement of capsular synthesis genes through bacterial transformation and recombination. Because the major antigen of current meningococcal vaccines is serogroup-specific, strains that undergo capsular switching may escape immune surveillance in immunized hosts. For example, a person harboring serogroup C that undergoes switching to serogroup B may develop illness from serogroup B organisms even though they have antibody to serogroup C as a result of immunization.
Which of the following is a property of conjugate vaccines that is absent in polysaccharide vaccines?
Answer: All of the above
Because conjugate vaccines are T-cell-dependent, (Viagra) they induce persistent protection and long-term immune memory. The presence of immune memory allows for robust booster effects on rechallenge. In addition, the reduction of carriage can prevent transmission to unimmunized persons in a population, resulting in herd immunity.
According to the ACIP, routine immunization against meningococcal disease is recommended for which of the following groups?
Answer: All of the above
The 2008 ACIP recommendations for immunization against meningococcal disease include all persons 11-18 years of age, those 2-55 years of age at increased risk, those traveling to endemic areas, persons with terminal complement deficiencies or asplenia, those with HIV, college freshmen living in dormitories, and laboratory workers exposed to N. meningitidis.
The CDC has estimated that immunizing all US 11-year-olds against meningococcal disease would result in which of the following?
Answer: Prevention of 359 cases
To estimate the potential impact of routine immunization on the incidence of GBS in the US population, the CDC modeled outcomes for vaccination of the entire cohort of US 11-year-olds, estimating that 359 cases and 35 deaths would be prevented. The model predicted 5 new cases of GBS, although it was estimated that only 0.18 cases would result in serious disability.
Which of the following is a component of an investigational vaccine against serogroup B that has been shown to be immunogenic in infants?
Answer: Factor H binding protein
The recombinant protein GNA 1870 was developed based on data from the genomic sequencing of N. meningitidis. This product was identified as factor H binding protein, which elicits bacterial activity by the classical complement pathway and inhibits binding of factor H to the bacterial surface. This protein, together with other proteins and outer membrane vesicles, is the basis of an investigational vaccine against serogroup B that has been shown to be immunogenic in infants.

1. Which of the following statements about the epidemiology of smoking and trends in smoking cessation is most accurate?
The prevalence of smoking in the United States has been stable in the period between 1965 and 1990
Over 40% of adult smokers reported attempting to quit in the preceding 12 months in 2006
Most smokers trying to quit seek assistance
A study of adult smokers demonstrated that 80% had received advice to quit smoking from health professionals
2. Which of the following medications appears most effective in promoting smoking cessation?
Nicotine replacement patches
Inhaled nicotine replacement therapy
Varenicline
Bupropion SR (sustained release)
3. All of the following potential adverse events are correctly matched with their associated smoking cessation therapy, except:
Nicotine replacement patches - itching and erythema
Bupropion SR - weight gain
Bupropion SR - suicidal tendencies
Varenicline - depression and suicidal ideation
4. Which of the following statements about psychological and behavioral interventions for smoking is most accurate?
Both group and individual therapy can double quit rates compared with no intervention
Duration of counseling sessions has no effect on abstinence from smoking
Telephone counseling has not been demonstrated to promote abstinence from smoking
Most patients proceed through stages of change related to smoking cessation in a linear fashion

Answers:

Which of the following statements about the epidemiology of smoking and trends in smoking cessation is most accurate?
Answer: Over 40% of adult smokers reported attempting to quit in the preceding 12 months in 2006
The prevalence of smoking decreased by 40% in the United States between 1965 and 1990, but 80% of smokers who desire to quit do not seek assistance. Research has found that most smokers do not receive advice to quit smoking from health professionals.
Which of the following medications appears most effective in promoting smoking cessation?
Answer: Varenicline
Varenicline has been associated with superior rates of smoking cessation compared with nicotine replacement therapy and bupropion SR in both clinical trials and systematic reviews.
All of the following potential adverse events are correctly matched with their associated smoking cessation therapy, except:
Answer: Bupropion SR - weight gain
Bupropion SR may reduce the degree of weight gain associated with smoking cessation. The other potential adverse events are correctly matched with their medical therapies.
Which of the following statements about psychological and behavioral interventions for smoking is most accurate?
Answer: Both group and individual therapy can double quit rates compared with no intervention
Longer counseling sessions to promote smoking cessation have been associated with higher abstinence rates. Telephone counseling has been demonstrated to be effective in promoting smoking cessation. Most patients experience relapses back to previous stages of change as they try to quit smoking.

1. All of the following patient characteristics are associated with improved response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) except:
Patients who are never smokers
Female patients
Patients with wild-type EGFR
Asian patients
None of the above
2. In the phase 3 INTEREST trial, gefitinib was found to be noninferior to docetaxel in the refractory setting. What was the median overall survival for gefitinib in this study?
4.0 months
5.2 months
6.4 months
7.6 months
8.8 months
3. In the phase 3 FLEX trial, what was the difference in overall survival in patients who received cetuximab in combination with cisplatin/vinorelbine vs cisplatin/vinorelbine alone?
9.7 months vs 8.5 months, respectively
10.6 months vs 9.3 months, respectively
11.3 months vs 10.1 months, respectively
12.0 months vs 10.9 months, respectively
None of the above
4. Which of the following statements is true?
Overexpression of EGFR predicts response to anti-EGFR therapies
Increased EGFR gene copy number detected by fluorescent in situ hybridization (FISH) predicts increased sensitivity to EGFR TKIs
Somatic mutations in the kinase domain of EGFR in lung cancer are weakly predictive of response to EGFR TKIs
HER2 amplification predicts decreased sensitivity to EGFR TKI inhibitors
None of the above
5. All of the following statements regarding EGFR inhibitor-associated rash are true except:
Rash has been associated with anticancer activity in both single-agent and combination trials
The TRIBUTE and TALENT trials with erlotinib found that patients who experienced rash demonstrated improved survival
The role of skin rash as a marker for activity with EGFR inhibitors has been studied extensively and is no longer controversial
The association between rash and response has been observed with cetuximab in other tumor types
None of the above

Answers:

All of the following patient characteristics are associated with improved response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) except:
Answer: Patients with wild-type EGFR
The discovery of specific EGFR mutations during clinical trials for anti-EGFR agents led to further study of the potential clinical impact of these mutations regarding treatment personalization. Somatic mutations in the kinase domain of EGFR in lung cancer have been shown to be strongly associated with sensitivity to EGFR TKIs. The somatic mutations are observed with increased frequency in women and in nonsmokers; this is underscored by the finding that 3 factors — whether the patient is a nonsmoker, Asian, or female — are associated independently and collectively with improved response to EGFR TKIs.
In the phase 3 INTEREST trial, gefitinib was found to be noninferior to docetaxel in the refractory setting. What was the median overall survival for gefitinib in this study?
Answer: 7.6 months
The phase 3 INTEREST (Iressa Non-small-cell lung cancer Trial Evaluating REsponse and Survival against Taxotere) trial, conducted in 1466 patients with NSCLC who had received 1 or 2 prior chemotherapy regimens, found gefitinib to be noninferior for survival (median OS of 7.6 months; 1-year survival of 32%) compared with docetaxel and offered improved tolerability and patient quality of life.
In the phase 3 FLEX trial, what was the difference in overall survival in patients who received cetuximab in combination with cisplatin/vinorelbine vs cisplatin/vinorelbine alone?
Answer: 11.3 months vs 10.1 months, respectively
The phase 3 FLEX (First-Line treatment for patients with epidermal growth factor inhibitor [EGFR]-EXpressing advanced NSCLC) trial of cetuximab combined with vinorelbine/cisplatin recently met its primary endpoint of increasing overall survival compared with chemotherapy alone in 1125 patients with advanced NSCLC and evidence of EGFR expression. While median progression-free survival was the same in both treatment groups (4.8 months), median overall survival was 11.3 months in the group that received cetuximab vs 10.1 months in the group that received chemotherapy alone (P = .044)
Which of the following statements is true?
Answer: Increased EGFR gene copy number detected by fluorescent in situ hybridization (FISH) predicts increased sensitivity to EGFR TKIs
Overexpression of EGFR does not appear to predict response to anti-EGFR therapies. Increased EGFR gene copy number detected by FISH predicts increased sensitivity to EGFR TKIs. Somatic mutations in the kinase domain of EGFR in lung cancer (often, in-frame exon 19 deletions or the L858R mutation) are strongly predictive of response to EGFR TKIs. HER2 amplification predicts increased sensitivity to EGFR TKI inhibitors, and HER2 kinase domain mutations (in-frame insertions in exon 20) are associated with resistance to EGFR TKI inhibitors. K-Ras testing may help identify the patients most likely to benefit from treatment with cetuximab as well as TKIs by excluding those with K-Ras mutations. The EGFR T790M mutation in exon 20 has been identified as an important mechanism of acquired resistance to reversible EGFR TKIs.
All of the following statements regarding EGFR inhibitor-associated rash are true except:
Answer: The role of skin rash as a marker for activity with EGFR inhibitors has been studied extensively and is no longer controversial
The role of skin rash as a marker for activity with EGFR inhibitors has been studied extensively and remains somewhat controversial. Rash has been associated with anticancer activity in both single-agent and combination EGFR inhibitor trials; the mechanism underlying this effect is unclear. While the TRIBUTE and TALENT trials did not show a benefit with the addition of erlotinib compared with chemotherapy alone in NSCLC, patients who experienced rash did demonstrate improved survival. Similar outcomes have been noted in trials with cetuximab plus chemotherapy in other tumor types.

1. In a patient with colorectal cancer, the presence of a K-Ras mutation in the primary tumor predicts:
Sensitivity to treatment with an EGF receptor inhibitor
A high level of EGF receptor expression
Resistance to treatment with an EGF receptor inhibitor
A low level of the ligand amphiregulin
2. Testing K-Ras status on tumor biopsies from patients with colorectal or lung cancer:
Can only be conducted by a few specialized laboratories around the world
Can be conducted by any quality laboratory using either institutionally developed tests or commercial kits
Is a very rapid procedure, with results reported within 24 hours
Often yields results that are difficult to interpret
3. Which of the following is not a consequence of better patient selection with the use of a standard biomarker, such as K-Ras status?
Improved therapeutic efficacy
Improved safety profile (lower exposure to side effects); improved quality of life
Reduced overall costs
Broader reimbursement by third party or government payors of all available treatments

Answers:

In a patient with colorectal cancer, the presence of a K-Ras mutation in the primary tumor predicts:
Answer: Resistance to treatment with an EGF receptor inhibitor
Data from several phase 3 clinical trials have validated K-Ras mutations as markers of resistance to treatment with EGF receptor inhibitors in colorectal cancer. Those patients whose tumors — regardless of whether biopsies were obtained from primary or metastatic sites — harbor mutations in the K-Ras oncogene are not expected to respond to anti-EGF receptor therapy. On the other hand, those with wild-type tumors have differing degrees of response to EGF receptor inhibitors, varying perhaps according to EGF receptor ligand level. Research on EGF receptor ligands as markers of sensitivity to EGF inhibitors is ongoing.
Testing K-Ras status on tumor biopsies from patients with colorectal or lung cancer:
Answer: Can be conducted by any quality laboratory using either institutionally developed tests or commercial kits
Testing tumor biopsies for mutations in the K-Ras oncogene can be conducted by most experienced pathologists in qualified institutional or commercial laboratories. Results are usually available within 7-10 days and provide a definitive “yes-or-no” answer regarding the status of the oncogene, namely wild-type or mutated.
Which of the following is not a consequence of better patient selection with the use of a standard biomarker, such as K-Ras status?
Answer: Broader reimbursement by third party or government payors of all available treatments
Although many benefits — such as improved efficacy, safety, quality of life, and cost — accrue from better patient selection, reimbursement of treatment based on K-Ras status will narrow payments only for those with documented wild-type tumors. In most European countries, EGF receptor inhibitors are indicated only for treatment of patients with wild-type tumors and can be reimbursed only when used as labeled. In the United States, coverage will probably still be approved in the chemorefractory colorectal setting, either alone or in combination with FOLFIRI, but this is likely to change in the near future.