Diabetes and pancreatic cancer risk in a multiracial cohort.

AIMS: To determine the relationship of diabetes with pancreatic cancer incidence among African American and Whites of similar socio-economic status. METHODS: Using the Southern Community Cohort Study, we conducted a follow-up during 2002-2015 of pancreatic cancer incidence of 73,378 mostly low-income participants aged 40-79 years; 15,913 reported diabetes at baseline. Multivariable Cox analysis controlling for sex, family history of pancreatic cancer, BMI, smoking status, alcohol consumption, education, income and other important covariates, and with age as the timescale was used. RESULTS: Totally, 265 incident pancreatic cancer cases were observed. Pancreatic cancer risk was increased among those with diabetes (HR 1.54, CI 1.16-2.05), with similar increases among African Americans (HR 1.51, CI 1.08-2.11) and Whites (HR 1.78, CI 1.00-3.16). No trend in risk was observed for diabetes duration among those with diabetes, with HRs of 1.39 (0.91-2.11), 2.31 (1.51-3.54) and 1.23 (0.80-1.89) for <5, 5-9 and 10+ years duration, respectively. African Americans were at increased risk of pancreatic cancer (HR = 1.40, 95% CI 1.05-1.87), which persisted after adjusting for diabetes (HR 1.36, CI 1.02-1.81). The effect sizes for other pancreatic cancer risk factors with pancreatic cancer were similar by diabetes status, although a stronger association with low BMI was evident among those with diabetes. CONCLUSIONS: Diabetes increases pancreatic cancer risk similarly among African Americans and Whites in this Southern U.S.

Hepatitis C Virus Infection Preceding an Outbreak of Human Immunodeficiency Virus Among Persons Who Inject Drugs-Kanawha County, West Virginia, 2019-2021.

Of 65 cases during a human immunodeficiency virus (HIV) outbreak among persons who inject drugs (PWID) in West Virginia (2019-2021), 61 (94%) had hepatitis C diagnosed a median of 46 months prior to HIV diagnosis. Hepatitis C diagnosis among PWID should trigger improved access to prevention and treatment services.

Standardized flattening filter free volumetric modulated arc therapy plans based on anteroposterior width for total body irradiation.

In this work, the feasibility of using flattening filter free (FFF) beams in volumetric modulated arc therapy (VMAT) total body irradiation (TBI) treatment planning to decrease protracted beam-on times for these treatments was investigated. In addition, a methodology was developed to generate standardized VMAT TBI treatment plans based on patient physical dimensions to eliminate plan optimization time. A planning study cohort of 47 TBI patients previously treated with optimized VMAT ARC 6 MV beams was retrospectively examined. These patients were sorted into six categories depending on height and anteroposterior (AP) width at the umbilicus. Using Varian Eclipse, clinical 40 cm × 10 cm open field arcs were substituted with 6 MV FFF. Mid-plane lateral dose profiles in conjunction with relative arc output factors (RAOF) yielded how far a given multileaf collimator (MLC) leaf must move in order to achieve a mid-plane 100% isodose for a specific control point. Linear interpolation gave the dynamic MLC aperture for the entire arc for each patient AP width category, which was subsequently applied through Python scripting. All FFF VMAT TBI plans were then evaluated by two radiation oncologists and deemed clinically acceptable. The FFF and clinical VMAT TBI plans had similar Body-5 mm D98% distributions, but overall the FFF plans had statistically significantly increased or broader Body-5 mm D2% and mean lung dose distributions. These differences are not considered clinically significant. Median beam-on times for the FFF and clinical VMAT TBI plans were 11.07 and 18.06 min, respectively, and planning time for the FFF VMAT TBI plans was reduced by 34.1 min. In conclusion, use of FFF beams in VMAT TBI treatment planning resulted in dose homogeneity similar to our current VMAT TBI technique. Clinical dosimetric criteria were achieved for a majority of patients while planning and calculated beam-on times were reduced, offering the possibility of improved patient experience.

Extended SSD VMAT treatment for total body irradiation.

In this work, we develop a total body irradiation technique that utilizes arc delivery, a buildup spoiler, and inverse optimized multileaf collimator (MLC) motion to shield organs at risk. The current treatment beam model is verified to confirm its applicability at extended source-to-surface distance (SSD). The delivery involves 7-8 volumetric modulated arc therapy arcs delivered to the patient in the supine and prone positions. The patient is positioned at a 90° couch angle on a custom bed with a 1 cm acrylic spoiler to increase surface dose. Single-step optimization using a patient CT scan provides enhanced dose homogeneity and limits organ at risk dose. Dosimetric data of 109 TBI patients treated with this technique is presented along with the clinical workflow. Treatment planning system (TPS) verification measurements were performed at an extended SSD of 175 cm. Measurements included: a 4-point absolute depth-dose curve, profiles at 1.5, 5, and 10 cm depth, absolute point-dose measurements of an treatment field, 2D Gafchromic® films at four locations, and measurements of surface dose at multiple locations of a Alderson phantom. The results of the patient DVH parameters were: Body-5 mm D98 95.3 ± 1.5%, Body-5 mm D2 114.0 ± 3.6%, MLD 102.8 ± 2.1%. Differences between measured and calculated absolute depth-dose values were all <2%. Profiles at extended SSD had a maximum point difference of 1.3%. Gamma pass rates of 2D films were greater than 90% at 5%/1 mm. Surface dose measurements with film confirmed surface dose values of >90% of the prescription dose. In conclusion, the inverse optimized delivery method presented in the paper has been used to deliver homogenous dose to over 100 patients. The method provides superior patient comfort utilizing a commercial TPS. In addition, the ability to easily shield organs at risk is available through the use of MLCs.

Evaluation of target and cardiac position during visually monitored deep inspiration breath-hold for breast radiotherapy.

A low-resource visually monitored deep inspiration breath-hold (VM-DIBH) technique was successfully implemented in our clinic to reduce cardiac dose in left-sided breast radiotherapy. In this study, we retrospectively characterized the chest wall and heart positioning accuracy of VM-DIBH using cine portal images from 42 patients. Central chest wall position from field edge and in-field maximum heart distance (MHD) were manually measured on cine images and compared to the planned positions based on the digitally reconstructed radiographs (DRRs). An in-house program was designed to measure left anterior descending artery (LAD) and chest wall separation on the planning DIBH CT scan with respect to breath-hold level (BHL) during simulation to determine a minimum BHL for VM-DIBH eligibility. Systematic and random setup uncertainties of 3.0 mm and 2.6 mm, respectively, were found for VM-DIBH treatment from the chest wall measurements. Intrabeam breath-hold stability was found to be good, with over 96% of delivered fields within 3 mm. Average treatment MHD was significantly larger for those patients where some of the heart was planned in the field compared to patients whose heart was completely shielded in the plan (p < 0.001). No evidence for a minimum BHL was found, suggesting that all patients who can tolerate DIBH may yield a benefit from it.

Erythrocyte omega-6 and omega-3 fatty acids and mammographic breast density.

Diets low in omega-6 (n-6) polyunsaturated fatty acids (PUFAs) and high in omega-3 (n-3) PUFAs may protect against breast cancer development. Associations of PUFA intake with mammographic density, an intermediate marker of breast cancer risk, have been inconsistent; however, prior studies have relied on self-reported dietary PUFA intake. We examined the association between circulating erythrocyte n-6 and n-3 PUFAs with mammographic density in 248 postmenopausal women who were not taking exogenous hormones. PUFAs in erythrocytes were measured by gas-liquid chromatography, and mammographic density was assessed quantitatively by planimetry. Spearman's correlation coefficients and generalized linear models were used to evaluate the relationships between PUFA measures and mammographic density. None of the erythrocyte n-6 or n-3 PUFA measures were associated with percent density or dense breast area.

Cancer incidence in elderly West Virginians.

West Virginia has one of the oldest populations in the nation. Cancer is a common disease among the elderly. With the projected growth of the elderly population (defined as 65 years and older), cancer will become a major public health burden. This article provides a summary of cancer incidence in elderly West Virginians. Incidence data were obtained from the West Virginia Cancer Registry. Approximately 6,262 elderly persons are diagnosed with some form of reportable cancer in West Virginia each year. Among those aged 65 and older, the four leading primary cancer sites in the order of their relative frequency were lung and bronchus cancer (21.8%), prostate cancer (14.6%), colorectal cancer (12.7%), and female breast cancer (9.6%). In general, the burden of cancer was greater in elderly men than in elderly women. Knowledge of the epidemiology of cancer in the elderly can potentially help guide statewide cancer prevention and control efforts and be used for anticipating future health care needs in the state.

Advanced automated treatment planning for total body irradiation: Implementation and effects on standardization.

PURPOSE: This work describes the automation of our volumetric modulated arc therapy (VMAT) total body irradiation (TBI) treatment planning. It also aims to determine if plan standardization is impacted by automation. METHODS: We introduced automated beam placement for TBI in March 2021. For manual beam placement pre-2021, Python-modified DICOM files were imported to pre-set cumulative meterset weights, with other parameters selected by dosimetrists. Our automated planning script automates these processes and sets gantry stop angles and isocentre placement. To determine the impact of automation on plan standardization, we performed a retrospective review of a matched cohort of 168 patients. Plan parameters were compared with an external standard, and passing rates compared between patient cohorts. The dosimetric impact was investigated by comparing a Body-5 mm homogeneity index (HI = D2%/D98%) and mean lung dose (MLD) between cohorts. RESULTS: Results are listed for manual and automated groups respectively. Median (range) passing rates were 97.7% (96.1-100) and 99.2% (98.3-100). Automated plans had a significantly higher passing rate (p â‰ª 0.05) and smaller variance (p = 0.001). Most failures were attributed to human error. Automated plans also had more consistent parameter identifiers. After considering dimensional outliers, median (range) Body-5 mm HI were 1.18 (1.14-1.23) and 1.18 (1.15-1.26), and mean ± standard deviation MLD were 103.8 ± 1.3% and 104.1 ± 0.9%. Variances were not significantly different between Body-5 mm HI (p = 0.092) but were for MLD (p = 0.013). CONCLUSIONS: Implementation of automated planning in TBI resulted in significantly improved plan standardization. The decrease in variance of the MLD for the automated planning group points towards a potential dosimetric benefit of automation.

Nonsteroidal anti-inflammatory drug use and serum total estradiol in postmenopausal women.

Laboratory and epidemiologic evidence suggest that nonsteroidal anti-inflammatory drug (NSAID) use may be inversely related to the risk of breast cancer; however, the mechanism by which NSAIDs may protect against the development of this disease is uncertain. The objective of this observational study was to assess the relationship between current NSAID use and endogenous estradiol levels, an established breast cancer risk factor. To evaluate this aim, we conducted a cross-sectional investigation among 260 postmenopausal women who were not recently exposed to exogenous hormones. Information on current NSAID use (aspirin, cyclooxygenase-2 inhibitors, and other NSAIDs combined) was collected using a questionnaire at the time of blood draw. Estradiol was quantified in serum by radioimmunoassay. General linear models were used to evaluate the association between NSAID use and serum total estradiol. The age-adjusted and body mass index-adjusted geometric mean serum estradiol concentration among NSAID users (n = 124) was significantly lower than nonusers of NSAIDs (n = 136; 17.8 versus 21.3 pmol/L; P = 0.03). Further adjustment for additional potential confounding factors did not substantially alter estimates (17.7 versus 21.2 pmol/L; P = 0.03). To our knowledge, this report is the first to examine the relationship between NSAID use and serum estradiol in postmenopausal women. These cross-sectional findings suggest that NSAID use may be associated with lower circulating estradiol levels, potentially representing one mechanism through which NSAIDs exert protective effects on breast cancer.

Radiation therapy for deep periocular cancer treatments when protons are unavailable: is combining electrons and orthovoltage therapy beneficial?

Deep periocular cancers can be difficult to plan and treat with radiation, given the difficulties in apposing bolus to skin, and the proximity to the retina and other optic structures. We sought to compare the combination of electrons and orthovoltage therapy (OBE) with existing modalities for these lesions. Four cases-a retro-orbital melanoma (Case 1) and basal cell carcinomas, extending across the eyelid (Case 2) or along the medial canthus (Cases 3-4)-were selected for comparison. In each case, radiotherapy plans for electron only, 70% electron and 30% orthovoltage (OBE), volumetric-modulated arc therapy (VMAT), conformal arc, and protons were compared. Dose-volume histograms for planning target volume coverage and selected organs at risk (OARs) were then calculated. The V90% coverage of the planning target volume was >98% for electrons, VMAT, conformal arc and proton plans and 90.2% and 89.5% in OBE plans for Cases 2 and 3, respectively. The retinal V80% was >98% in electron, VMAT and proton plans and 79.4%; and 87.1% in OBE and conformal arcs for Case 2 and 91.3%, 36.4%, 56.9%, 52.4% and 43.7% for Case 3 in electrons, OBE, VMAT, conformal arc and proton plans, respectively. Protons provided superior coverage, homogeneity and OAR sparing, compared with all other modalities. However, given its simplicity and widespread availability, OBE is a potential alternative treatment option for moderately deep lesions where bolus placement is difficult.

Effects of a vegetarian diet and treatment preference on biochemical and dietary variables in overweight and obese adults: a randomized clinical trial.

BACKGROUND: A vegetarian diet may lead to numerous health benefits, including weight loss. OBJECTIVE: We examined the joint effects of personal preference of dietary treatment and a calorie-restricted, low-fat lactoovovegetarian diet (LOV-D) compared with a standard calorie-restricted, low-fat omnivorous diet (STD-D) on changes in weight, total cholesterol, ratio of LDL to HDL cholesterol (LDL:HDL cholesterol), triacylglycerols, insulin resistance, and macronutrient intake during an 18-mo study. DESIGN: This was a randomized clinical trial of 176 overweight and obese adults who were recruited and randomly assigned first to 1 of 2 preference conditions (yes or no). If assigned to Preference-No, they were randomly assigned to 1 of the 2 diet conditions (STD-D or LOV-D). If assigned to Preference-Yes, they were assigned to the diet they indicated as preferred at screening. The 12-mo intervention was followed by a 6-mo maintenance phase. RESULTS: Participants were mainly women (86.9%) and white (70.5%); 75% completed the 18-mo study. A significant interaction between preference and dietary treatment was not observed for any of the outcome variables. However, participants in the Preference-No groups significantly decreased their triacylglycerols (P = 0.04). The only effect observed for diet was a borderline significant decrease in LDL:HDL cholesterol for the LOV-D group (P = 0.06). Within the LOV-D groups, those who were 100% adherent to the LOV-D had significant and marginally significant reductions in monounsaturated fat (P = 0.02) and total fat (P = 0.05) intakes at 18 mo. CONCLUSIONS: Our findings suggest that neither prescribing a vegetarian diet nor allowing persons to choose their preferred diet had a significant effect on outcome measures. However, all participants had a significant reduction in total energy and fat intakes and an increase in energy expenditure, which was reflected in reduced body weight. This clinical trial was registered at www.clinicaltrials.gov as NCT00330629.

Survival was Significantly Better with Surgical/Medical/Radiation Co-interventions in a Single-Institution Practice Audit of Frameless Stereotactic Radiosurgery.

PURPOSE: To audit outcomes after introducing frameless stereotactic radiosurgery (SRS) for brain metastases, including co-interventions: neurosurgery, systemic therapy, and whole brain radiotherapy (WBRT). We report median overall survival (MS), local failure, and distant brain failure. We hypothesized patients treated with SRS would have clinically meaningful improved MS compared with historic institutional values. We further hypothesized that patients treated with co-interventions would have clinically meaningful improved MS compared with patients treated with SRS alone. METHODS: One hundred twenty patients (N = 120) with limited intracranial disease underwent 130 frameless SRS sessions from April 2010 to May 2013. Median follow-up was 11 months. MS was measured from brain metastases diagnosis, local failure, and distant brain failure from the time of first SRS. RESULTS: Practice pattern during the first year of the study favored upfront WBRT (79%) over SRS (21%) while upfront SRS (45%) was almost as common as upfront WBRT (55%) in the last year of the study. MS was 18 months; 37% received SRS alone as initial radiotherapy (MS 12 months); 63% received WBRT prior to SRS (MS 19 months); 50% received systemic therapy post-SRS (MS 21 months); and 26% had tumor resection then SRS to the surgical cavity (MS 42 months). Local failure occurred in 10% of lesions and radio-necrosis occurred in 4%. Differences in distant brain failure among patients treated with upfront SRS (40% rate), WBRT followed by SRS (33% rate) or systemic therapy post-SRS (37% rate) were not statistically significant. CONCLUSION: Frameless SRS effectively treats surgical cavities, persistent tumors post-WBRT, and can be used as an upfront treatment of brain metastases. Surgery, systemic therapy, and WBRT are associated with longer MS. Patients can live for years while receiving multiple therapies. Systemic therapy for patients with brain metastases is increasingly common, palliative care occurs earlier and improves survival, and WBRT use is not routine. Modern series sometimes produce unexpectedly good results. Classification and treatment protocols are evolving. This practice audit is note-worthy for (i) high median overall survival, (ii) systemic therapy after radiosurgery for patients with tumors treated by radiosurgery, (iii) distant brain failure not significantly related to WBRT, and (iv) neurosurgery, systemic therapy, and WBRT are independently associated with improved MS.

Cardiac dose reduction with deep inspiration breath hold for left-sided breast cancer radiotherapy patients with and without regional nodal irradiation.

BACKGROUND: Deep inspiration breath hold (DIBH) reduces heart and left anterior descending artery (LAD) dose during left-sided breast radiation therapy (RT); however there is limited information about which patients derive the most benefit from DIBH. The primary objective of this study was to determine which patients benefit the most from DIBH by comparing percent reduction in mean cardiac dose conferred by DIBH for patients treated with whole breast RT ± boost (WBRT) versus those receiving breast/chest wall plus regional nodal irradiation, including internal mammary chain (IMC) nodes (B/CWRT + RNI) using a modified wide tangent technique. A secondary objective was to determine if DIBH was required to meet a proposed heart dose constraint of Dmean < 4 Gy in these two cohorts. METHODS: Twenty consecutive patients underwent CT simulation both free breathing (FB) and DIBH. Patients were grouped into two cohorts: WBRT (n = 11) and B/CWRT + RNI (n = 9). 3D-conformal plans were developed and FB was compared to DIBH for each cohort using Wilcoxon signed-rank tests for continuous variables and McNemar's test for discrete variables. The percent relative reduction conferred by DIBH in mean heart and LAD dose, as well as lung V20 were compared between the two cohorts using Wilcox rank-sum testing. The significance level was set at 0.05 with Bonferroni correction for multiple testing. RESULTS: All patients had comparable target coverage on DIBH and FB. DIBH statistically significantly reduced mean heart and LAD dose for both cohorts. Percent reduction in mean heart and LAD dose with DIBH was significantly larger in the B/CWRT + RNI cohort compared to WBRT group (relative reduction in mean heart and LAD dose: 55.9 % and 72.1 % versus 29.2 % and 43.5 %, p < 0.02). All patients in the WBRT group and five patients (56 %) in the B/CWBRT + RNI group met heart Dmean <4 Gy with FB. All patients met this constraint with DIBH. CONCLUSIONS: All patients receiving WBRT met Dmean Heart < 4 Gy on FB, while only slightly over half of patients receiving B/CWRT + RNI were able to meet this constraint in FB. DIBH allowed a greater reduction in mean heart and LAD dose in patients receiving B/CWRT + RNI, including IMC nodes than patients receiving WBRT. These findings suggest greatest benefit from DIBH treatment for patients receiving regional nodal irradiation.

Cobalt, linac, or other: what is the best solution for radiation therapy in developing countries?

The international growth of cancer and lack of available treatment is en route to become a global crisis. With >60% of cancer patients needing radiation therapy at some point during their treatment course, the lack of available facilities and treatment programs worldwide is extremely problematic. The number of deaths from treatable cancers is projected to increase to 11.5 million deaths in 2030 because the international population is aging and growing. In this review, we present how best to answer the need for radiation therapy facilities from a technical standpoint. Specifically, we examine whether cobalt teletherapy machines or megavoltage linear accelerator machines are best equipped to handle the multitudes in need of radiation therapy treatment in the developing world.

A framework for the implementation of new radiation therapy technologies and treatment techniques in low-income countries.

We present a practical, generic, easy-to-use framework for the implementation of new radiation therapy technologies and treatment techniques in low-income countries. The framework is intended to standardize the implementation process, reduce the effort involved in generating an implementation strategy, and provide improved patient safety by reducing the likelihood that steps are missed during the implementation process. The 10 steps in the framework provide a practical approach to implementation. The steps are, 1) Site and resource assessment, 2) Evaluation of equipment and funding, 3) Establishing timelines, 4) Defining the treatment process, 5) Equipment commissioning, 6) Training and competency assessment, 7) Prospective risk analysis, 8) System testing, 9) External dosimetric audit and incident learning, and 10) Support and follow-up. For each step, practical advice for completing the step is provided, as well as links to helpful supplementary material. An associated checklist is provided that can be used to track progress through the steps in the framework. While the emphasis of this paper is on addressing the needs of low-income countries, the concepts also apply in high-income countries.

Implementation of a high-dose-rate brachytherapy program for carcinoma of the cervix in Senegal: a pragmatic model for the developing world.

West Africa has one of the highest incidence rates of carcinoma of the cervix in the world. The vast majority of women do not have access to screening or disease treatment, leading to presentation at advanced stages and to high mortality rates. Compounding this problem is the lack of radiation treatment facilities in Senegal and many other parts of the African continent. Senegal, a country of 13 million people, had a single (60)Co teletherapy unit before our involvement and no brachytherapy capabilities. Radiating Hope, a nonprofit organization whose mission is to provide radiation therapy equipment to countries in the developing world, provided a high-dose-rate afterloading unit to the cancer center for curative cervical cancer treatment. Here we describe the implementation of high-dose-rate brachytherapy in Senegal requiring a nonstandard fractionation schedule and a novel treatment planning approach as a possible blueprint to providing this technology to other developing countries.

Assessing the burden of HPV-related cancers in Appalachia.

Appalachia is a geographic region with existing cancer disparities, yet little is known about its burden of HPV-related cancers outside of cervical cancer. We assessed the burden of HPV-related cancers in three Appalachian states and made comparisons to non-Appalachian regions. We examined 1996-2008 cancer registry data for Ohio, Kentucky, West Virginia and the Surveillance, Epidemiology and End Results (SEER) 9 program. For each gender, we calculated age-adjusted incidence rates per 100,000 population for each HPV-related cancer type (cervical, vaginal, vulvar, penile, anal and oral cavity and pharyngeal cancers) and all HPV-related cancers combined. Incidence rates among females for all HPV-related cancers combined were higher in Appalachian Kentucky [24.6 (95% CI: 23.5-25.7)], West Virginia [22.8 (95% CI: 22.0-23.6)] and Appalachian Ohio [21.9 (95% CI: 21.0-22.8)] than SEER 9 [18.8 (95% CI: 18.6-19.0)]. Similar disparities were found among females when examining cervical and vulvar cancers separately. Among males, Appalachian [21.3 (95% CI: 20.2-22.4)] and non-Appalachian [21.9 (95% CI: 21.2-22.7)] Kentucky had higher incidence rates for all HPV-related cancers combined than SEER 9 [18.3 (95% CI: 18.1-18.6)]. The incidence rate of all HPV-related cancers combined was higher among males from Appalachian Ohio compared with those from non-Appalachian Ohio [17.6 (95% CI: 16.8-18.5) vs. 16.3 (95% CI: 16.0-16.6)]. Our study suggests that HPV-related cancer disparities exist in Appalachia beyond the known high cervical cancer incidence rates. These results have important public health implications by beginning to demonstrate the potential impact that widespread HPV vaccination could have in Appalachia.