Cancer Research Priorities Research Articles

Colorectal cancer research priorities in Uganda: perspectives from local key experts and stakeholders.

The incidence of colorectal cancer (CRC) is increasing in Uganda but there is limited local research to guide policy and programming for CRC prevention and control. A stakeholder engagement workshop took place in Kampala on 19March 2024 to identify challenges and opportunities for CRC prevention and control in Uganda. A total of 30 stakeholders with expertise in CRC primary and secondary prevention, diagnosis, treatment, palliative care as well as cancer survivors participated in the workshop. Key challenges for primary prevention included low knowledge/awareness of CRC among the general population and health workers, and rising prevalence of CRC related risk factors. Limited CRC screening, diagnostic facilities and specialists were identified as barriers to diagnosis. Treatment related challenges included limited accessibility to surgical services and drugs, late-stage presentation leading to poor treatment response, treatment abandonment and drug related toxicity. Lack of universal health coverage policies, limited community-based cancer awareness programs, and lack of national cancer registries were cited as policy and economics challenges. Opportunities to address these challenges were discussed. Our findings highlight areas for further research and prioritization to address Uganda's growing CRC burden and may be applicable to other low-resource settings.

Autophagy is required for mammary tumor recurrence by promoting dormant tumor cell survival following therapy

BackgroundMortality from breast cancer is principally due to tumor recurrence. Recurrent breast cancers arise from the pool of residual tumor cells, termed minimal residual disease, that survive treatment and may exist in a dormant state for 20 years or more following treatment of the primary tumor. As recurrent breast cancer is typically incurable, understanding the mechanisms underlying dormant tumor cell survival is a critical priority in breast cancer research. The importance of this goal is further underscored by emerging evidence suggesting that targeting dormant residual tumor cells in early-stage breast cancer patients may be a means to prevent tumor recurrence and its associated mortality. In this regard, the role of autophagy in dormant tumor cell survival and recurrence remains unresolved, with conflicting reports of both pro-survival/recurrence-promoting and pro-death/recurrence-suppressing effects of autophagy inhibition in dormant tumor cells. Resolving this question has important clinical implications.MethodsWe used genetically engineered mouse models that faithfully recapitulate key features of human breast cancer progression, including minimal residual disease, tumor dormancy, and recurrence. We used genetic and pharmacological approaches to inhibit autophagy, including treatment with chloroquine, genetic knockdown of ATG5 or ATG7, or deletion of BECN and determined their effects on dormant tumor cell survival and recurrence.ResultsWe demonstrate that the survival and recurrence of dormant mammary tumor cells following therapy is dependent upon autophagy. We find that autophagy is induced in vivo following HER2 downregulation and remains activated in dormant residual tumor cells. Using genetic and pharmacological approaches we show that inhibiting autophagy by chloroquine administration, ATG5 or ATG7 knockdown, or deletion of a single allele of the tumor suppressor Beclin 1 is sufficient to inhibit mammary tumor recurrence, and that autophagy inhibition results in the death of dormant mammary tumor cells in vivo.ConclusionsOur findings demonstrate a pro-tumorigenic role for autophagy in tumor dormancy and recurrence following therapy, reveal that dormant tumor cells are uniquely reliant upon autophagy for their survival, and indicate that targeting dormant residual tumor cells by inhibiting autophagy impairs tumor recurrence. These studies identify a pharmacological target for a cellular state that is resistant to commonly used anti-neoplastic agents and suggest autophagy inhibition as an approach to reduce dormant minimal residual disease in order to prevent lethal tumor recurrence.

Tobacco-cannabis co-use among cancer patients and survivors: findings from 2 US cancer centers.

Cannabis use is prevalent among cancer patients and survivors and may provide some therapeutic benefits for this population. However, benefits may be attenuated when cannabis is co-used with tobacco, which is associated with more severe tobacco and cannabis use and adverse outcomes in noncancer populations. We compared cannabis use, primary mode of use, and therapeutic and/or nontherapeutic use among 3 groups of patients and survivors based on cigarette smoking status. Survey data was collected from patients and survivors with cancer (n = 1732) at 2 US National Cancer Institute-designated cancer centers in states with varying cannabis regulatory policy. Prevalence of cannabis use (prior to diagnosis, after diagnosis, before treatment, after treatment), primary mode of use, and therapeutic and/or nontherapeutic use were assessed by cigarette smoking status (current, former, never) within and across centers using weighted bivariate analyses and multivariable logistic regression, controlling for demographic and clinical variables. Current cigarette use was associated with greater rates of cannabis use prior to diagnosis, after diagnosis, during treatment, and after treatment within each center (all P < .001) and in pooled analyses across centers (all P < .001). Primary mode of use, knowledge of cannabis products, and therapeutic and/or nontherapeutic use also statistically differed by tobacco status and study site. Results illustrate the importance of conducting assessments for both tobacco and cannabis use among cancer patients during and after cancer treatment, regardless of the cannabis regulatory environment. Given previous data indicating harms from co-use and continued tobacco use during cancer treatment, this issue introduces new priorities for cancer care delivery and research.

Therapy-Induced Senescence: Novel Approaches for Markers Identification.

Therapy-induced senescence (TIS) represents a major cellular response to anticancer treatments. Both malignant and non-malignant cells in the tumor microenvironment undergo TIS and may be harmful for cancer patients since TIS cells develop a senescence-associated secretory phenotype (SASP) that can sustain tumor growth. The SASP also modulates anti-tumor immunity, although the immune populations involved and the final results appear to be context-dependent. In addition, senescent cancer cells are able to evade senescence growth arrest and to resume proliferation, likely contributing to relapse. So, research data suggest that TIS induction negatively affects therapy outcomes in cancer patients. In line with this, new interventions aimed at the removal of senescent cells or the reprogramming of their SASP, called senotherapy, have become attractive therapeutic options. To date, the lack of reliable, cost-effective, and easy-to-use TIS biomarkers hinders the application of recent anti-senescence therapeutic approaches in the clinic. Hence, the identification of biomarkers for the detection of TIS tumor cells and TIS non-neoplastic cells is a high priority in cancer research. In this review article, we describe the current knowledge about TIS, outline critical gaps in our knowledge, and address recent advances and novel approaches for the discovery of TIS biomarkers.

Summary and Roadmap of Breast Cancer Research in the Veterans Affairs.

Women are the largest growing population of Veterans within the U.S. Department of Veterans Affairs (VA) Health Care System. Among women Veterans, breast cancer is the most common malignancy (30% of all cancers), yet little is known about the unique needs of women Veterans with cancer and how to provide them with high quality care. The VA health care system has initiated multiple system-wide systemic efforts, including launching the Breast and Gynecologic Cancer System of Excellence (BGSOE) to address this knowledge gap. This report summarizes the outcomes of the inaugural 2023 VA Women's Cancer Research Conference, which assembled 37 multidisciplinary clinicians, scientists, the VA and civilian partners with a shared goal of advancing VA breast cancer research. Conference objectives were to build a collective vision for improving: (1) referral patterns for breast cancer treatment and patient-level outcomes and (2) molecular and genetic testing patterns across the breast cancer continuum among women Veterans. The meeting hosted 15 speakers at the Houston VA Medical Center. Future research priorities for women Veterans with cancer were identified from discussions and a post-conference survey. We then administered a 13-question post-conference survey to conference attendees. Respondents ranked the research priorities. The survey results show that the cross-cutting cancer research priorities designed to transform cancer care for women Veterans at the VA fit into 5 broad areas of study, including (1) care quality for treatment, (2) improving treatment, (3) care quality of molecular and genetic testing, (4) risk reduction through risk assessment and germline genetic testing, and (5) establishing strategic partnerships. Our data elucidate areas for further investigation to improve the delivery of cancer care.

Is there scope to do better? Clinical communication with adolescents and young adults with cancer-A scoping review.

How to communicate effectively with adolescent and young adults with cancer (AYACs) is a research priority. In a UK-wide survey of young people with cancer's research priorities, communication was a striking cross-cutting theme. It is increasingly recognised that AYACs have experiences and communication needs that differ significantly from those of younger children and older adults. The purpose of this review is to explore the features of effective clinical communication with AYACs. A literature search was undertaken to identify and map the available evidence using a broad scope to get an overview of the pertinent literature, identify knowledge gaps and clarify concepts. The searches yielded 5825 records, generating 4040 unique articles. These were screened and 71 full articles were read by four researchers with disagreements resolved by discussion leaving 29 included articles. Narrative synthesis was undertaken in relation to each of the research questions. Three key themes were identified: being an adolescent/young adult, supporters, and healthcare professionals (HCPs). AYACs need to feel that HCPs understand their unique perspective. They want to be involved, this changes over time and in different contexts. Supporters are a central tenet, are most often parents and undertake several roles which are not always universally supportive. HCPs enable involvement of AYACs, and this needs to be actively promoted. AYACs preference for their level of involvement requires continual assessment. The three themes are interlinked and exist within the wider scope of the triadic encounter and cancer experience. Supporters, most often parents were a key feature across the data and were seemingly paradoxical in nature. Triadic communication, the presence of a third person, is a central tenet of communication with AYACs and we propose a conceptual model to represent the nuances, components, and facets of this complex communication.

Cancer in general practice research priorities in Australia.

The Primary Care Collaborative Cancer Clinical Trials Group (PC4) is funded by Cancer Australia to support the development of new cancer in primary care research. We undertook a research prioritisation exercise to identify cancer research priorities in Australian general practice. We adapted the nominal group technique, including a literature search and stakeholder survey. An expert group from the Primary Care Collaborative Cancer Clinical Trials Group consolidated and ranked priorities. A second stakeholder survey reviewing the top 50 priorities informed a final prioritisation workshop. Overall, 311 priorities were identified across the cancer continuum. Nearly one-third of priorities were related to cancer survivorship and included strategies to detect recurrence, behavioural interventions and tools to assess physical and psychosocial aspects of survivorship. Prevention/early detection comprised 43.4% of priorities. Palliative care produced the least priorities (9.6%). Cross cutting research priorities (15.1%) included quality and models of care. This is the first study to identify cancer research priorities for general practice in Australia. It could be used to inform the development of targeted research and funding to improve the care and outcomes for Australians affected by cancer.

Demographic Analysis of Cancer Research Priorities and Treatment Correlations.

Understanding the diversity in cancer research priorities and the correlations among different treatment modalities is essential to address the evolving landscape of oncology. This study, conducted in collaboration with the European Cancer Patient Coalition (ECPC) and Childhood Cancer International-Europe (CCI-E) as part of the "UNCAN.eu" initiative, analyzed data from a comprehensive survey to explore the complex interplay of demographics, time since cancer diagnosis, and types of treatments received. Demographic analysis revealed intriguing trends, highlighting the importance of tailoring cancer research efforts to specific age groups and genders. Individuals aged 45-69 exhibited highly aligned research priorities, emphasizing the need to address the unique concerns of middle-aged and older populations. In contrast, patients over 70 years demonstrated a divergence in research priorities, underscoring the importance of recognising the distinct needs of older individuals in cancer research. The analysis of correlations among different types of cancer treatments underscored the multidisciplinary approach to cancer care, with surgery, radiotherapy, chemotherapy, precision therapy, and biological therapies playing integral roles. These findings support the need for personalized and combined treatment strategies to achieve optimal outcomes. In conclusion, this study provides valuable insights into the complexity of cancer research priorities and treatment correlations in a European context. It emphasizes the importance of a multifaceted, patient-centred approach to cancer research and treatment, highlighting the need for ongoing support, adaptation, and collaboration to address the ever-changing landscape of oncology.

Aligning Cancer Research Priorities in Europe with Recommendations for Conquering Cancer: A Comprehensive Analysis.

Improvements in cancer care require a new degree of collaboration beyond the purely medical sphere, extending deeply into the world of other stakeholders-preeminently patients but also the other stakeholders in the hardware and software of care. Cancer remains a global health challenge, necessitating collaborative efforts to understand, prevent, and treat this complex disease. To achieve this goal, a comprehensive analysis was conducted, aligning the prioritization of cancer research measures in 13 European countries with 13 key recommendations for conquering cancer in the region. The study utilized a survey involving both patients and citizens, alongside data from IQVIA, a global healthcare data provider, to assess the availability and access to single-biomarker tests in multiple European countries. The results revealed a focused approach toward understanding, preventing, and treating cancer, with each country emphasizing specific research measures tailored to its strengths and healthcare objectives. This analysis highlights the intricate relationship between research priorities, access to biomarker tests, and financial support. Timely access to tests and increased availability positively influence research areas such as cancer prevention, early detection, ageing, and data utilization. The alignment of these country-specific measures with 13 recommendations for conquering cancer in Europe underscores the importance of tailored strategies for understanding, preventing, and treating cancer.

Priorities for cancer research and innovation in Low- and middle-income countries

The World Bank classifies economies for analytical purposes into four income groups: low, lower-middle, upper-middle, and high-income. For this purpose, it uses gross national income (GNI) per capita data in U.S. dollars, converted from local currency using the World Bank Atlas (Figure 1), which is applied to smooth exchange rate fluctuations (1). Noncommunicable diseases (NCDs) were identified as one major challenge to sustainable development in low- and middle-income countries (LMICs). Most deaths globally are now due to NCDs, with cancer being responsible for at least 20 % of all mortality (2). Although the overall incidence of cancer is lower in LMICs compared with high-income countries (HICs), total cancer-related mortality is significantly higher in LMICs, especially for people ≤65 years of age; the more significant economic impact because of premature mortality and lost years of productivity is a particular problem for these limited resources environments (3). In 2020, 75 % of all global deaths attributable to NCDs, including cancer, occurred in LMICs, with nearly 50 % of deaths considered to be premature (4,5).

Moving forward through consensus: a national Delphi approach to determine the top research priorities in prostate cancer in Uganda

ObjectiveTo identify key areas for research in prostate cancer (PC) in the Ugandan context by establishing the major health system, socioeconomic and clinical barriers to seeking, reaching and receiving high-quality...

Redefining Cancer Research Priorities in Low- and Middle-Income Countries in the Post-COVID-19 Global Context: A Modified Delphi Consensus Process.

The post-COVID-19 funding landscape for cancer research globally has become increasingly challenging, particularly in resource-challenged regions (RCRs) lacking strong research ecosystems. We aimed to produce a list of priority areas for cancer research in countries with limited resources, informed by researchers and patients. Cancer experts in lower-resource health care systems (as defined by the World Bank as low- and middle-income countries; N = 151) were contacted to participate in a modified consensus-seeking Delphi survey, comprising two rounds. In round 1, participants (n = 69) rated predetermined areas of potential research priority (ARPs) for importance and suggested missing ARPs. In round 2, the same participants (n = 49) rated an integrated list of predetermined and suggested ARPs from round 1, then undertook a forced choice priority ranking exercise. Composite voting scores (T-scores) were used to rank the ARPs. Importance ratings were summarized descriptively. Findings were discussed with international patient advocacy organization representatives. The top ARP was research into strategies adapting guidelines or treatment strategies in line with available resources (particularly systemic therapy) (T = 83). Others included cancer registries (T = 62); prevention (T = 52); end-of-life care (T = 53); and value-based and affordable care (T = 51). The top COVID-19/cancer ARP was strategies to incorporate what has been learned during the pandemic that can be maintained posteriorly (T = 36). Others included treatment schedule interruption (T = 24); cost-effective reduction of COVID-19 morbidity/mortality (T = 19); and pandemic preparedness (T = 18). Areas of strategic priority favored by cancer researchers in RCRs are related to adaptive treatment guidelines; sustainable implementation of cancer registries; prevention strategies; value-based and affordable cancer care; investments in research capacity building; epidemiologic work on local risk factors for cancer; and combatting inequities of prevention and care access.

Prevalence, trends, and characteristics of trials investigating local therapy in contemporary phase 3 clinical cancer research.

Although most patients with cancer are treated with local therapy (LT), the proportion of late-phase clinical trials investigating local therapeutic interventions is unknown. The purpose of this study was to determine the proportion, characteristics, and trends of phase 3 cancer clinical trials assessing the therapeutic value of LT over time. This was a cross-sectional analysis of interventional randomized controlled trials in oncology published from 2002 through 2020 and registered on ClinicalTrials.gov. Trends and characteristics of LT trials were compared to all other trials. Of 1877 trials screened, 794 trials enrolling 584,347 patients met inclusion criteria. A total of 27 trials (3%) included a primary randomization assessing LT compared with 767 trials (97%) investigating systemic therapy or supportive care. Annual increase in the number of LT trials (slope [m]=0.28; 95% confidence interval [CI], 0.15-0.39; p<.001) was outpaced by the increase of trials testing systemic therapy or supportive care (m=7.57; 95% CI, 6.03-9.11; p<.001). LT trials were more often sponsored by cooperative groups (22 of 27 [81%] vs. 211 of 767 [28%]; p<.001) and less often sponsored by industry (5 of 27 [19%] vs. 609 of 767 [79%]; p<.001). LT trials were more likely to use overall survival as primary end point compared to other trials (13 of 27 [48%] vs. 199 of 767 [26%]; p=.01). In contemporary late-phase oncology research, LT trials are increasingly under-represented, under-funded, and evaluate more challenging end points compared to other modalities. These findings strongly argue for greater resource allocation and funding mechanisms for LT clinical trials. Most people who have cancer receive treatments directed at the site of their cancer, such as surgery or radiation. We do not know, however, how many trials test surgery or radiation compared to drug treatments (that go all over the body). We reviewed trials testing the most researched strategies (phase 3) completed between 2002 and 2020. Only 27 trials tested local treatments like surgery or radiation compared to 767 trials testing other treatments. Our study has important implications for funding research and understanding cancer research priorities.

Ethnically diverse communities and their priorities for cancer research.

e18602 Background: Ethnic minorities in the UK tend to have poorer access to healthcare, outcomes and experiences than the majority population. They are often underrepresented in health research. Experiencing disparities compounded by the lack of involvement in research widens the inequalities gap. Methods: Targeted community engagement was implemented in the highest areas of deprivation in the South West. The project team designed a series of questions and data was collected during outreach health checks and community events by members of the team based in the community. Information was collected from individuals and from groups. Results: Forty people, from culturally and linguistically diverse communities participated. We sought help from interpreters to ensure inclusivity and information was gathered in a cultural sensitive way. This was especially important due to the sensitivity in this topic area. Demographic information was collected from those that participated. The majority were women (n = 33), men (n = 7). In terms of ethnicity the majority described themselves as Black African/Caribbean (n = 31), Arab (n = 9) and Asian (n = 3). The age range was 25 - 64 years. Twelve people identified that their actual age was different to their recorded age on the NHS system. Fourteen people had been in the UK for less than 5 years and included those identifying themselves as refugees and asylum seekers. We conducted content analysis to identify and categorise the cancer research needs identified. Key themes identified included: Easier access to screening programmes; earlier diagnosis and how to initiate onward referral; research into cancer prevention and a more holistic approach to cancer care. Only one patient had clinical trials discussed. Conclusions: Community engagement offers the opportunity to identify cancer research priorities and discuss access to cancer prevention, cancer screening programmes, therapies and clinical trials. Through actively listening to our communities and the voices seldom heard about their experience of health and cancer care, we raise awareness and provide ongoing education to health care teams, on the delivery of care that is culturally sensitive, inclusive and more tailored to an individual. Increasing the diversity of the workforce may increase representation and greater advocacy of the communities. Engaging patients more in their own cancer care and decision-making may empower them to be more involved in their health. Our findings suggest that community engagement with people from diverse communities identify areas for improvement in their cancer care and experience. This includes how we might better engage with people from diverse backgrounds on clinical trials. Addressing the priorities identified from these communities is a first step in addressing the existing inequalities. Organisations need to actively engage, listen to and empower the communities that we serve.

Top 10 research priorities in colorectal cancer: results from the Colorectal Cancer Priority-Setting Partnership

Top 10 research priorities in colorectal cancer: results from the Colorectal Cancer Priority-Setting Partnership

Patients' and carers' priorities for cancer research in Aotearoa/New Zealand.

Discrepancies have been reported between what is being researched, and what patients/families deem important to be investigated. Our aim was to understand research priorities for those who live with cancer in Aotearoa/New Zealand, with emphasis on Māori. Adult outpatients with cancer and their whānau/family completed a survey (demographics, selecting keywords, free-text comments) at Christchurch hospital. Quantitative and qualitative data were evaluated using standard statistical and thematic analyses, respectively. We recruited 205 participants, including both tūroro/patients (n = 129) and their whānau/family/carer (n = 76). Partnership with Māori health workers enabled greater recruitment of Māori participants (19%), compared to the proportion of Māori in Canterbury (9%). Cancer research was seen as a priority by 96% of participants. Priorities were similar between Māori and non-Māori participants, with the keywords 'Cancer screening', 'Quality of Life' and 'Development of new drugs' chosen most often. Free-text analysis identified three themes; 'Genetics and Prevention', 'Early Detection and Treatment', and 'Service Delivery', with some differences by ethnicity. Cancer research is a high priority for those living with cancer. In addition, participants want researchers to listen to their immediate and practical needs. These findings may inform future cancer research in Aotearoa. Aotearoa (New Zealand) he aha ō whakaaro (what are your thoughts) hui (gathering) mate pukupuku (cancer) mokopuna (descendent) Ōtautahi (Christchurch) rongoā (traditional healing) tāne (male) te reo (Māori language) Te Whatu Ora (weaving of wellness, Health New Zealand) tikanga (methods, customary practices) tūroro (patients) (alternative terms used: whānau affected by cancer or tangata whaiora (person seeking health)) wahine (female) Waitaha (Canterbury) whakapapa (genealogy) whānau ((extended) family, based on whakapapa, here also carer).

Groundshot: a pan-European, patient-centred, and data-driven approach to tackling cancer

In 2017, inspired by the US Cancer Moonshot initiative, The Lancet Oncology published a Commission on cancer research priorities in the USA. Writing in a Comment reflecting on this Commission from a European perspective, Fortunato Ciardiello and Josep Tabernero remarked, “as scientists and doctors working in Europe, we…believe that The Lancet Oncology Commission presents research priorities that must also be discussed within the European Union (EU)...[because]…large disparities in national cancer research programmes and actions in cancer care still exist between EU countries.” This astute observation has become even more complicated in the intervening years because of the UK's exit from the EU (Brexit), the COVID-19 pandemic, the Russian invasion of Ukraine, the cost-of-living crisis, and the impending risk of a global recession.

CN75 The impact of cancer on financial and work-related needs: Lymphoma-specific concerns

Lymphoma survivors are at increased risk of unmet needs due to cancer, its treatment-related toxicities and extended survivorship. Despite the rapidly increasing numbers of lymphoma cancer survivors, their needs and research priorities are underserved and undervalued, therefore left unaddressed. This research aimed to establish an understanding of the unmet needs of people living with or beyond a lymphoma diagnosis.

PDL1 Positivity Rate Between Triple-negative and Non-luminal Her2+ Cases

Background: Triple-negative breast cancer cases with no available targeted therapy and advanced cases of luminal and HER2+ that become resistant to available state-of-the-art treatments are priorities in cancer research. Immune checkpoint blockade, particularly PDL1/PD1 inhibition, is suggested as a potential option for these patients suffering from several other types of cancers, such as melanoma. However, the exact subpopulation of breast cancer patients that overexpress PDL1 is yet to be completely identified. Additionally, reports on the value of PDL1 as a biomarker for the prognosis of cancer and its correlation with clinicopathological features of malignancy are diverse. Method: In this study, we performed immunohistochemistry on 60 breast cancer, including 22 triple-negative and 38 HER2+ cases, and 20 paired lymph node samples. Results: PDL1 expression was present in 21. 6% (13/60) of breast cancer samples. PDL1 expression is significantly associated with ER/PR negativity and the grade of the tumor. The association between PDL1 positivity and recurrence and the overall survival of patients was not significant. Conclusion: PDL1 expression is similar between triple-negative and non-luminal HER2+ cases, thus some of the advanced non-luminal HER2+ cases might be benefitted from immune checkpoint blockade.

Cancer Groundshot: Building a Robust Cancer Control Platform in Addition To Launching the Cancer Moonshot.

Cancer Groundshot is a philosophy that calls for prioritization of strategies in global cancer control. The underlying principle of Cancer Groundshot is that one must ensure access to interventions that are already proven to work before focusing on the development of new interventions. In this article, we discuss the philosophy of Cancer Groundshot as it pertains to priorities in cancer care and research in low- and middle-income countries and the utility of technology in addressing global cancer disparities; we also address disparities seen in high-income countries. The oncology community needs to realign our priorities and focus on improving access to high-value cancer control strategies, rather than allocating resources primarily to the development of technologies that provide only marginal gains at a high cost. There are several "low-hanging fruit" actions that will improve access to quality cancer care in low- and middle-income countries and in high-income countries. Worldwide, cancer morbidity and mortality can be averted by implementing highly effective, low-cost interventions that are already known to work, rather than investing in the development of resource-intensive interventions to which most patients will not have access (i.e., we can use Cancer Groundshot to first save more lives before we focus on the "moonshots").