Miller, Robert C.

Radiation oncology is poised for a decade of unusually rapid technological and biological change. Six innovations are converging on the clinic: FLASH radiotherapy, adaptive radiotherapy with advanced imaging, artificial intelligence and machine learning in treatment planning, theranostics with targeted radionuclide therapy, spatially fractionated radiotherapy using GRID and LATTICE techniques, and continuing enhancements in particle therapy with protons and heavy ions. Each is biologically compelling, but they will not reach patients at the same speed or in equal numbers. This review proposes an evidence-and-capital framework for evaluating these innovations along four axes – physical principle, biological rationale, current clinical evidence, and dominant adoption barrier – and ranks them by anticipated population-level impact over the next five years. Capital intensity emerges as the principal determinant of diffusion: innovations layered onto existing linear accelerators (artificial intelligence, spatially fractionated radiotherapy) or onto existing nuclear medicine infrastructure (theranostics) will scale globally, whereas innovations requiring new bunkers, magnetic-shielded vaults, or dedicated accelerators (adaptive radiotherapy, FLASH, particle therapy) will remain concentrated in well-resourced centres. A low anticipated diffusion ranking is not a judgement on intrinsic clinical value: several capital-intensive modalities deliver substantial benefit for selected patients even where population-level reach is limited, and the framework distinguishes throughout between intrinsic efficacy and expected accessibility. The resulting equity gap is not primarily a scientific problem but an infrastructural one. Recognising this asymmetry should inform departmental investment, training curricula, multinational cooperative-group trial design, and health-system policy on capital subsidy and consortium models. The framework is intended for radiation oncologists, medical physicists, and cancer scientists evaluating where to invest finite institutional resources.

Background: Biobanks often lack standard mechanisms to keep donors connected to their biospecimens, reflecting a broken feedback loop that compromises trust, engagement, and scientific progress. Decentralized biobanking empowers patients to track their donations throughout the research journey, supporting personalized feedback and research collaboration via a privacy-preserving blockchain network. This case study explores operational feasibility of implementing decentralized biobanking for a large breast cancer biobank at a US academic medical center. Methods: A mixed-methods case study of the groundwork, implementation, and stakeholder feedback for a real-world decentralized biobanking app pilot was conducted. Biobank members were recruited from February to April 2023. Operational feasibility was assessed via analysis of institutional stakeholder perspectives, pilot engagement, and de-bi app activity. Findings: Physicians and other biobank stakeholders surfaced challenges surrounding managing expectations, balancing empowerment with clinical and research workflows, and navigating power dynamics between patients, physicians, scientists, and leadership. A total of 1080 participants enrolled over 10 weeks, including nearly 10% of the biobank with about 4000 biospecimens. During the pilot, biobank enrollment increased 65% versus the prior year, and there were no biobank withdrawals during or within 1 year following the pilot ( p < 0.001 for both). The app, which facilitated biospecimen tracking and research engagement, was downloaded by 405 users. A total of 140 users tested the blockchain component, with 89% successfully claiming a nonfungible token representing their unique, immutable connection and access to donated biospecimens. Feedback was solicited to inform potential process improvements and risk assessments related to public relations, systems infrastructure, and ethical governance, illuminating next steps. Conclusions: We established operational feasibility for the first step toward decentralized biobanking, informed by requirements to manage expectations, workflows, and power dynamics. Our technical solution demonstrated robust participant engagement and compatibility with established biobanks, suggesting potential to build trust and align incentives and identifying next steps for communications, sustainability, and governance.

212 Background: Endometrial cancer significantly impacts the Appalachian population compared to the overall United States population. Evidence supports that this difference may be due to health disparities, which includes access to affordable healthy food, obesity, and metabolic syndromes in addition to care disparities. Methods: We queried the Kentucky Cancer Registry’s online public Cancer Incidence and Mortality Registry to determine changes in age adjusted invasive corpus uteri cancer incidence and mortality rates in Appalachian (AK) and Non-Appalachian Kentucky (NAK) counties over time. Incidence rate ratios were used to analyze the difference in endometrial cancer incidence and mortality between AK and NAK populations across several time periods. The z-test for two population proportions was used to analyze differences in incidence and mortality between AK and NAK. Results: Incidence of endometrial cancer was higher in AK vs. NAK at the beginning (P < 0.002) and end (P < 0.001) of the period examined, although there was no statistically significant difference in mortality between AK vs NAK. Incidence and mortality increased in both AK (P < 0.01) and NAK (P < 0.001) across the period studied. Conclusions: Incidence in endometrial cancer in Appalachian Kentucky was significantly higher than non-Appalachian Kentucky, although mortality was not higher in the final years studied. Lower socioeconomic status, access to affordable nutritious foods, and health likely contributed to an increased incidence of endometrial cancer. With an increase in chronic diseases such as obesity prevailing in AK, there is increased exposure to unopposed estrogen, which increases the risk for developing endometrial cancer and may be reflected in these results. Education and lack of access to healthcare also are contributing factors. Although the cancer care disparities seen in Appalachia are commonly viewed as byproducts of the region’s unique culture, they can also be viewed as local expression of challenges in global oncology facing resource poor, rural regions around the world. Efforts to reduce the risk in Appalachia will require addressing the underlying problems seen in other communities worldwide with rising endometrial cancer incidence – poverty, health literacy, obesity, rising rates of diabetes, exercise and environmental pollution. Year Incidence AK (/100,000) Incidence NAK (/100,000) % Higher Incidence AK Mortality AK (/100,000) Mortality NAK (/100,000) % Higher Mortality AK 2001-2005 25.3 21.0 20.5% 1.6 1.6 0.0% 2006-2010 27.2 22.1 23.1% 1.5 1.6 -6.3% 2011-2015 30.3 24.7 22.7% 2.0 1.7 17.6% 2016-2020 31.8 26.0 22.3% 2.5 2.6 -3.8%

e13809 Background: Endometrial cancer significantly impacts the Appalachian population compared to the overall United States population. Evidence supports that this difference may be due to health disparities, which includes access to affordable healthy food, obesity, and metabolic syndromes in addition to care disparities. Methods: We queried the Kentucky Cancer Registry’s online public Cancer Incidence and Mortality Registry to determine changes in age adjusted invasive corpus uteri cancer incidence and mortality rates in Appalachian (AK) and Non-Appalachian Kentucky (NAK) counties over time. Incidence rate ratios were used to analyze the difference in endometrial cancer incidence and mortality between AK and NAK populations across several time periods. The z-test for two population proportions was used to analyze differences in incidence and mortality between AK and NAK. Results: Incidence of endometrial cancer was higher in AK vs. NAK at the beginning (P < 0.002) and end (P < 0.001) of the period examined, although there was no statistically significant difference in mortality between AK vs NAK. Incidence and mortality increased in both AK (P < 0.01) and NAK (P < 0.001) across the period studied. Conclusions: Incidence in endometrial cancer in Appalachian Kentucky was significantly higher than non-Appalachian Kentucky, although mortality was not higher in the final years studied. Lower socioeconomic status, access to affordable nutritious foods, and health likely contributed to an increased incidence of endometrial cancer. With an increase in chronic diseases such as obesity prevailing in AK, there is increased exposure to unopposed estrogen, which increases the risk for developing endometrial cancer and may be reflected in these results. Education and lack of access to healthcare also are contributing factors. Although the cancer care disparities seen in Appalachia are commonly viewed as byproducts of the region’s unique culture, they can also be viewed as local expression of challenges in global oncology facing resource poor, rural regions around the world. Efforts to reduce the risk in Appalachia will require addressing the underlying problems seen in other communities worldwide with rising endometrial cancer incidence – poverty, health literacy, obesity, rising rates of diabetes, exercise and environmental pollution. Year Incidence AK (/100,000) Incidence NAK (/100,000) % Higher Incidence AK Mortality AK (/100,000) Mortality NAK (/100,000) % Higher Mortality AK 2001-2005 25.3 21.0 20.5% 1.6 1.6 0.0% 2006-2010 27.2 22.1 23.1% 1.5 1.6 -6.3% 2011-2015 30.3 24.7 22.7% 2.0 1.7 17.6% 2016-2020 31.8 26.0 22.3% 2.5 2.6 -3.8%

e15673 Background: Since the late 1990s, both the incidence and mortality of invasive colorectal cancer (CRC) have decreased across the United States, including in Kentucky. Despite this, CRC incidence and mortality are above national average in Kentucky. Over the last two decades, a disparity in CRC incidence and mortality has emerged between Appalachian Kentucky (AK), a distinct eastern region, and Non-Appalachian Kentucky (NAK). This disparity is attributed to differences in social and structural determinants of health (SSDH) between these populations. Methods: Age-adjusted CRC incidence and mortality rates (2016-2020) for both Kentucky and the U.S. were obtained from the National Cancer Institute’s public database. Data from the Kentucky Cancer Registry were used to compare CRC incidence and mortality rates in AK and NAK counties from 1994-2021. Incidence rate ratio analyses across discrete time periods demonstrated statistical differences between these regions. Results: Compared to national data (2016-2020), Kentucky's CRC age-adjusted incidence and mortality rates were significantly higher: 45.9 vs. 36.5/100,000, 25.8%, for incidence, and 16.2 vs. 13.1/100,000, 23.7%, for mortality (both p < 0.0001). From 1995-2003 incidence and 1994-2003 mortality of CRC, were higher in NAK, these rates eventually decreased and equalized between NAK and AK. By 2010-2015 both incidence and mortality rates were higher in AK, 55.8 vs 48/100,000, 16.3%, (p = < 0.0001) and 20.1 vs 15.8/100,000, 27.2%, (p = < 0.0001) respectively. The most recent data (2016-2021) shows that these significant disparities persist, with AK’s incidence and mortality 51.8 vs 44.1/100,000, 17.5% (p = < 0.0001) and mortality 19.0 vs 15.1/100,000, 25.8% (p = < 0.0001) higher, respectively. Conclusions: While CRC rates have decreased nationwide and in Kentucky, a pronounced gap in both incidence and mortality has developed between Appalachian and Non-Appalachian Kentucky. Appalachian counties—which are more rural and impoverished—face greater barriers to accessing preventive healthcare, contributing to this disparity. Additionally, AK has higher rates of obesity, poverty, smoking, and lower educational attainment and screening rates. Recent public health efforts, such as promoting stool-based screening and increasing preventive care discussions, aim to reduce these disparities. However, delays in CRC screenings during the COVID-19 pandemic— resulting in approximately 1.7 million missed colonoscopies nationally— may have skewed the most recent data, necessitating further analysis in the coming years.

33 Background: Since the late 1990s, both the incidence and mortality of invasive colorectal cancer (CRC) have decreased across the United States, including in Kentucky. Despite this, CRC incidence and mortality are above national average in Kentucky. Over the last two decades, a disparity in CRC incidence and mortality has emerged between Appalachian Kentucky (AK), a distinct eastern region, and Non-Appalachian Kentucky (NAK). This disparity is attributed to differences in social and structural determinants of health (SSDH) between these populations. Methods: Age-adjusted CRC incidence and mortality rates (2016-2020) for both Kentucky and the U.S. were obtained from the National Cancer Institute’s public database. Data from the Kentucky Cancer Registry were used to compare CRC incidence and mortality rates in AK and NAK counties from 1994-2021. Incidence rate ratio analyses across discrete time periods demonstrated statistical differences between these regions. Results: Compared to national data (2016-2020), Kentucky's CRC age-adjusted incidence and mortality rates were significantly higher: 45.9 vs. 36.5/100,000, 25.8%, for incidence, and 16.2 vs. 13.1/100,000, 23.7%, for mortality (both p<0.0001). From 1995-2003 incidence and 1994-2003 mortality of CRC, were higher in NAK, these rates eventually decreased and equalized between NAK and AK. By 2010-2015 both incidence and mortality rates were higher in AK, 55.8 vs 48/100,000, 16.3%, (p=<0.0001) and 20.1 vs 15.8/100,000, 27.2%, (p=<0.0001) respectively. The most recent data (2016-2021) shows that these significant disparities persist, with AK’s incidence and mortality 51.8 vs 44.1/100,000, 17.5% (p=<0.0001) and mortality 19.0 vs 15.1/100,000, 25.8% (p=<0.0001) higher, respectively. Conclusions: While CRC rates have decreased nationwide and in Kentucky, a pronounced gap in both incidence and mortality has developed between Appalachian and Non-Appalachian Kentucky. Appalachian counties—which are more rural and impoverished—face greater barriers to accessing preventive healthcare, contributing to this disparity. Additionally, AK has higher rates of obesity, poverty, smoking, and lower educational attainment and screening rates . Recent public health efforts, such as promoting stool-based screening and increasing preventive care discussions, aim to reduce these disparities. However, delays in CRC screenings during the COVID-19 pandemic— resulting in approximately 1.7 million missed colonoscopies nationally— may have skewed the most recent data, necessitating further analysis in the coming years.

132 Background: Cervical cancer continues to affect the Appalachian population to a higher degree than the rest of the American population. Researchers believe the increased prevalence of cervical cancer in the Appalachian area is due to health disparities across the area. Methods: We queried the Kentucky Cancer Registries online public Cancer Incidence and Mortality Inquiry System to determine changes in age adjusted invasive cervical cancer incidence and mortality rates in Appalachian (AK) and Non-Appalachian Kentucky (NAK) counties over time. Incidence rate ratios were used to analyze the difference in cervical cancer incidence and mortality between Appalachian KY and non-Appalachian KY populations across several time periods. Results: In 1995-1999, there was a statistically significant difference in cervical cancer incidence between AK and NAK 14.8 vs. 12.7/100,000 people (p= 0.0035) and mortality 4.6 vs. 4.0/100,000 (p=0.0471). The cervical cancer incidence was 16.9% higher in AK versus NAK and mortality was 18.4% higher in AK versus NAK. In 2016-2020, there was a statistically significant difference in cervical cancer incidence between AK and NAK 12.1 vs. 8.9/100,000 people (p≤ 0.0001) and mortality between AK and NAK 3.6 vs. 2.3/100,000 people (p= 0.0001). The cervical cancer incidence was 36% higher in AK versus NAK and mortality was 55.7% higher in AK versus NAK. Conclusions: Disparities between in Appalachian Kentucky and Non-Appalachian Kentucky in cervical cancer incidence and mortality not only have persisted since the 1990’s, but they have widened proportionally over time as survival gains have lagged in Appalachia. The observed cervical cancer outcome disparities are likely contributed to by not only the lack of general health education in the region, but more importantly barriers to care access contributing to a lower use of Pap testing in the area. Higher rates of poverty, increased rates of smoking and HPV infection also likely play a role. Research has been conducted to observe identified opportunities for intervention and begin collaborative efforts in the region engineered towards a cervical cancer risk reduction program, but the need for improvement clearly remains. Cervical cancer mortality rates in Appalachian Kentucky vs. non-Appalachian Kentucky, 1995-2020. Appalachia Non-Appalachia Population at Risk Deaths Crude Rate/100,000 Age-Adjusted Rate 95% Confidence Interval Population at risk Deaths Crude Rate/100,000 Age-Adjusted Rate 95% Confidence Interval 1995-1999 2928468 145 5 4.6 [3.9-5.4] 7209127 301 4.2 4 [3.6-4.5] 2000-2004 2962204 102 3.4 3.2 [2.6-3.9] 7485965 214 2.9 2.7 [2.3-3.1] 2005-2009 2986284 117 3.9 3.5 [2.9-4.2] 7833348 225 2.9 2.6 [2.3-3.0] 2010-2015 3577269 141 3.9 3.4 [2.8-4.0] 9803897 277 2.8 2.5 [2.2-2.9] 2016-2020 2941022 121 4.1 3.6 [3.0-4.4] 8378683 221 2.6 2.3 [2.0-2.7]

Granulomatous dermatitis is a common tissue reaction pattern seen in the skin or systematically in various presentations. Granulomatous dermatitis can be subclassified into infectious and non-infectious categories. This article focuses on a patient with non-infectious granulomatous dermatitis followed for many years. Past medical history included bilateral total shoulder arthroplasty complicated by prosthetic joint infections. In its early stages, the axillary rash was painful and had many fluid-filled blisters. Ultimately, the histology of the rash deemed the lesion non-infectious and mostly due to an inflammatory process. Specifically, ionizing radiation was used for this patient. The category of granulomatous processes is broad and there are many subtypes. Other treatment options for non-infectious granulomatous processes may include corticosteroids, phototherapy, and interferon-gamma injections. The differential for granulomatous processes is extensive and treatment should be decided on a case-by-case basis.