The University of Texas MD Anderson Cancer Center’s Moon Shots Program® is a collaborative effort to accelerate the development of scientific discoveries into clinical advances that save patients’ lives. The program was inspired by President John F. Kennedy’s speech in Houston in 1962, where he declared our nation’s mission to go to the moon. Launched in 2012, the Moon Shots Program® began under the leadership of then-President of the University of Texas MD Anderson Cancer Center, Dr. Ronald DePinho. During an interview describing the motivation behind the program, he stated, “Humanity urgently needs bold action to defeat cancer. I believe that we have many of the tools we need to pick the fight of the 21st century. Let us focus our energies on approaching cancer comprehensively and systematically, with the precision of an engineer, always asking … ‘What can we do to directly impact patients? ’”
Since its inception, the Moon Shots Program® has expanded to 13 multidisciplinary teams of clinicians and researchers tasked with developing comprehensive approaches to advance cancer prevention, early detection, and treatment to improve the lives of patients and reduce cancer mortality. In addition to launching innovative clinical trials and accelerating scientific research, the achievements of the Moon Shots Program® include public awareness campaigns for cancer prevention. These accomplishments include contributing to legislation banning teenage tanning bed use in Texas and other states, expanding a smoking cessation program, and expanding HPV vaccination efforts in the United States and globally. Furthermore, significant efforts have been made to detect cancer early when patient outcomes can be profoundly impacted. In this chapter, we highlight examples of the program’s success in reducing global cancer mortality, using three salient examples: promoting smoking cessation as part of the Lung Cancer Moon Shot, enhancing HPV vaccination as part of the HPV Moon Shot, and facilitating early detection of pancreatic cancer as part of the Pancreatic Cancer Moon Shot.
Lung Cancer Moon Shot: Smoking Cessation Initiatives
Smoking is a significant public health problem and is currently responsible for nearly 6 million premature deaths each year worldwide (including 480,000 in the United States alone), with estimates as high as 8 million deaths annually by the year 2030. Tobacco plays a causal role in at least 15 types of cancer , and accounts for 85% of lung cancer cases and approximately 30% of the attributable risk for overall cancer mortality. While there are several approved smoking cessation medications, including varenicline, bupropion, and several types of nicotine replacement therapy products (NRT), each with demonstrated efficacy against placebo, there is considerable heterogeneity in treatment response. Individual variation in response to medication, in particular, suggests that “one size does not fit all” and improving our understanding of individual-level predictors of treatment outcome is critical to the advancement of the field. One of our major challenges lies in determining how to optimize a smoker’s chance of achieving initial treatment success and what approaches should be taken at treatment failure. The potential to match smokers to a specific initial treatment based on factors observable prior to quitting (at baseline) has been investigated using a variety of behavioral, genetic, biological, affective, and neurobiological factors in an effort to predict the response to pharmacotherapy. However, matching patients to a “rescue” treatment after initial failure remains unclear, and there is little guidance for providers to select the optimal follow up treatment.
A second important challenge is the delivery of the most effective treatment to the largest group of smokers. National surveys show that less than one-third of smokers who attempt to quit actually receive counseling and pharmacotherapy. Traditional state “quitlines,” while offering a service to a large number of smokers at any one time, are highly underutilized and, in comparison to the most effective treatment approaches using both counseling and pharmacotherapy, are much less effective.
Smoking Cessation Solutions
To achieve the goal of changing clinical practice for smoking cessation, we initiated a series of prospective clinical trials and conducted an extensive analysis of genetic information from previously completed trials that collectively examined the relationship between specific individual-level predictors (behavioral, affective, neurophysiologic) and response to smoking cessation treatments. While each of these trials individually addressed specific research questions, the collective goal in this effort was to extract critical information from each trial regarding individual differences that can be used to predict, or personalize, response to various treatments, including pharmacotherapy and behavioral treatments. These factors include age, sex, motivation, nicotine dependence, affect, psychiatric comorbidity (depression), neural and behavioral indicators of brain deficits in reward, metabolic (nicotine metabolic ratio), and genetic profiles, and importantly, the specific treatment pathways (which medications or series of medications they use) before they successfully quit. In parallel, we also examined the optimal treatment configuration for delivering smoking cessation in the context of lung cancer screening, focusing on older age, heavy smokers who have not yet quit, and for whom additional genetic data on lung cancer risk will be available. We expect this study to provide additional individual-level information on predictors of treatment outcome for this unique population that can be related to lung cancer risk, and may further the development of a predictive algorithm.
In addition to identifying predictive markers of response, we have also worked to promulgate the basic cessation treatment model developed and refined within the MD Anderson Cancer Center Tobacco Treatment Program (TTP). TTP began modestly in 2006 with clinician referral, later incorporating automated referral using electronic health records. The program currently treats nearly 1200 new patients at MD Anderson and conducts more than 11,000 patient visits per year. The TTP is comprehensive, consisting of individualized smoking cessation counseling, over-the-counter and prescription pharmacotherapy, and the integrated assessment and treatment of mental health conditions and other psychosocial concerns. The TTP plan consists of an initial in-person consultation (60–90 min), plus 6–8 subsequent follow up treatment sessions conducted over an 8- to 12-week period, 95% of which were conducted by telephone. Treatment involves behavioral counseling for smoking cessation and other psychologic or psychiatric interventions, as needed, for related mental health issues. Counseling is based on the principles of motivational interviewing and social cognitive behavioral problem solving. Patients typically receive 10–12 weeks of pharmacotherapy, including nicotine replacement (patch or lozenge), bupropion, and varenicline, either alone or in various combinations. Each treatment plan is personalized in terms of counseling session number, duration, content, and choice of pharmacotherapy, which followed a previously defined protocol consistent with the National Comprehensive Cancer Network guidelines.
To determine the effectiveness of long-term abstinence and evaluate differences between patients with and without cancer, we analyzed data from more than 3000 individuals who received smoking cessation treatment through the MD Anderson TTP. Overall self-reported abstinence rates for the sample were 45.1% at 3 months, 45.8% at 6 months, and 43.7% at 9 months for the multiply imputed data (averaged over 10 imputed data sets), 41.1% at 3 months, 39.5% at 6 months, and 35.6% at 9 months for intention-to-treat (ITT); and 44.5% at 3 months, 45.6% at 6 months, and 43.7% at 9 months for respondents only. We also obtained expired carbon monoxide levels during all in-person visits. Congruence between self-reported, 7-day point prevalence abstinence and expired carbon monoxide was 93% for less than 8 ppm and 87% for carbon monoxide levels of less than 6 ppm. No significant differences in abstinence for the multiply imputed sample were found when comparing no cancer history versus cancer history at the 3-month (relative risk [RR], 1.03; 95% CI, 0.93–1.16; P = 0.55), 6-month (RR, 1.05; 95% CI, 0.94–1.18; P = 0.38), and 9-month (RR, 1.10; 95% CI, 0.97–1.26; P = 0.14) follow ups, as well as in the longitudinal models (RR, 1.06; 95% CI, 0.95–1.18; P = 0.27). In addition, no significant differences were noted in the comparisons of no cancer history versus those with and without smoking-related cancer (RR, 1.02; 95% CI, 0.90–1.14; P = 0.8) or patients with a history of cancer (RR, 1.04; 95% CI, 0.89–1.20; P = 0.64).
TTP dissemination occurs through two major initiatives within our Moon Shots Program®. First, we developed and oversaw the clinical content within an MD Anderson Cancer Center-certified tobacco treatment specialist training program (CTTS). This program successfully disseminates the TTP model to other health care systems and health care providers through direct training and supervision of counselors and providers from around the country. The second initiative provides clinical content and expertise for Project ECHO (Extension for Community Healthcare Outcomes), a telementoring program that provides expert consultation to providers across the country, based on the TTP treatment model.
HPV Cancer Moon Shot: The Global Burden of HPV-Associated Cancers
Human papillomavirus (HPV) infection causes nearly 5% of all new cancer cases globally, affecting the uterine cervix, vulva, vagina, anus, penis, and oropharynx. With approximately 530,000 new cases annually, cervical cancer is the most common HPV-associated cancer worldwide, compared to other HPV-associated cancers (113,000 annual cases). This global picture is driven by low- and middle-income countries (LMICs), where approximately 85% of new cases of cervical cancer occur mainly due to the lack of organized cervical screening and HPV vaccination programs ( Fig. 62.1 ). With the evolution of sexual practices in recent decades, an increasing incidence of HPV-related anal and oropharyngeal cancers has been observed. ,
Unlike LMICs, where cervical cancer is by far the most common HPV-related cancer, widespread screening programs in high-income countries (HICs) have dramatically reduced the burden of cervical cancer. To date, the burden of HPV-associated noncervical cancers outweighs that of cervical cancer in HICs. In the United States, where an average of 44,000 HPV-associated cancers are reported annually, oropharyngeal cancers (12,600) are more common than cervical cancers (9700).
HPV Vaccine Development, Evolution, and Recommendations
The discovery of HPV as the necessary cause of cervical cancer has led to the development of prophylactic HPV vaccines. The HPV vaccine is composed of self-assembled virus-like particles (VLPs) that form when a specific protein (the viral L1 major capsid protein) is produced by microorganisms (yeast for Gardasil, Merck) or insect cells (for Cervarix, GSK) through a fermentation process. These VLPs closely resemble native HPV particles and act as antigens that evoke the production of HPV-neutralizing antibodies in the human body. The vaccine does not contain DNA and is therefore considered noninfectious.
In 2006 the US Food and Drug Administration (FDA) approved the first commercially available prophylactic HPV vaccine, Gardasil (Merck & Co., USA), for the primary prevention of infections by HPV16 and HPV18, as well as HPV6 and HPV11, the two HPV genotypes that cause 90% of genital warts. In 2007 the Centers for Disease Control and Prevention’s Advisory Committee for Immunization Practices (ACIP) recommended routine HPV vaccination in women aged 9–26 years. In 2010 a second HPV vaccine for the primary prevention of infections by HPV16 and HPV18, Cervarix (GSK, Belgium), was approved by the FDA and recommended by the ACIP. Further, 4vHPV vaccination of males aged 9–26 years was approved by the US FDA in October 2009 and subsequently recommended by the ACIP in 2010.
In 2014 the FDA approved a second-generation vaccine, Gardasil 9 (9vHPV), which targets five additional HPV genotypes: HPV31, 33, 45, 52, and 58. Following this, the ACIP recommended in 2015 that routine HPV vaccination is initiated at 11 or 12 years of age but can be started as young as 9 years of age for females and males. Vaccination was also recommended for females and males aged 13–21 years and women aged 22–26 years who have not been vaccinated previously or who have not completed the three-dose series, and it was stated that males aged 22–26 years may be vaccinated. Since 2017 Gardasil-9 has been the only HPV vaccine available in the United States. In 2018 the FDA approved the use of the 9vHPV vaccine in adults aged 27–45 years, and in 2019 ACIP expanded its recommendation to this age group based on a shared clinical decision-making procedure.
Until 2016, the ACIP recommended a three-dose regimen for HPV vaccination (at M0, M1, and M6) regardless of age at initiation of HPV vaccination. In 2016 a two-dose (at M0 and M6) schedule was recommended for girls and boys who initiated the vaccination series at ages 9 through 14 years, but three doses remained the recommendation for persons who initiated the vaccination series at age ≥15 years and for immunocompromised persons.
Barriers to Implementation of HPV Vaccination
Despite progress achieved in recent years, HPV vaccination rates in the United States remain suboptimal. In 2018 only 51% of eligible adolescents were up to date on their vaccination schedule, far below the Healthy People 2020 goal of 80%, and below the rates achieved by other HICs, such as Australia, the United Kingdom, and Belgium. Many factors contribute to low HPV vaccination uptake in the United States. At the system or policy level, missed clinical opportunities to recommend and offer HPV vaccines constitute a major limiting factor. , This suggests the need for (i) health care organizations to use electronic office systems, including electronic health records and immunization information systems; (ii) the CDC to develop, test, disseminate, and evaluate the impact of integrated, comprehensive communication strategies for physicians and other relevant health professionals; (iii) Healthcare Effectiveness Data and Information Set quality measure for HPV vaccination to be expanded to males; and (iv) states to enact laws and implement policies that allow pharmacists to administer vaccines.
At the provider level, lack of high-quality recommendation for HPV vaccine to patients is a strong correlate of underutilization of HPV vaccine in the United States. At the individual or community level, people’s knowledge, perception, and acceptance of the HPV vaccine is limited. In a study assessing the reasons for not receiving HPV vaccine among eligible US adults, the most frequently reported reasons were as follows: did not know about the vaccine (18.5% [14.9–22.1]), provider did not recommend (14.1% [10.9–17.4]), vaccine not needed or necessary (13.8% [10.0–17.0]), not sexually active (13.7% [10.5–16.9]), and not required to get the vaccine (11.4% [8.5–14.3]) ( Fig. 62.2 ). In another US study examining beliefs about HPV vaccine effectiveness in preventing cervical cancer, only 29.8% of women believed that HPV vaccine is successful in preventing cervical cancer.
Global Examples of Vaccine Efficacy/Effectiveness and Success in Overcoming Barriers
Of the nearly 100 countries that have introduced HPV vaccination, only a few have achieved vaccination higher than 80% coverage. , This includes Australia in Oceania, Scotland in Europe, Bhutan in Asia, and Rwanda in Africa. Overall, analysis of the average reported coverage by delivery strategy shows that countries using school-based vaccination had, on average, 20% higher coverage than those providing vaccines through primary care or health centers.
In Australia, parental opinions were key drivers of vaccination, with HPV vaccination associated with the parent being the vaccine decision-maker and with previous completion of the childhood vaccination schedule. In Austria, where males and females are vaccinated, information on the vaccine from physicians was found to strongly influence vaccine uptake. In that country, higher paternal educational status has shown to significantly increase boy’s HPV vaccination but did not influence girl’s vaccination, suggesting that sex-specific strategies may be required. In 2011, following a national education and awareness campaign, Rwanda was the first LMIC to implement a national HPV vaccination program. Since then, Rwanda has achieved more than 90% coverage with 4vHPV vaccination every year, through school-based vaccination and community outreach to females absent from or not enrolled in school. The roll-out of HPV vaccination nationally through the Merck Donation Program (2011–2013) served as the “demonstration” necessary to become a GAVI-supported program in 2013.
In the United States, HPV vaccination rates vary widely across states ( Fig. 62.3 ). The states that have enacted the HPV vaccination mandate have achieved the highest coverage rates (Rhode Island, District of Columbia) and the largest annual increase in HPV vaccination rates (Virginia), and the most conservative and highly religious states (Wyoming, Mississippi, South Carolina, Utah, and Texas) exhibit the lowest HPV vaccination rates and/or a decrease in HPV vaccination uptake.