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Animal brain-tumor models have demonstrated a synergistic interaction between radiation therapy and a ketogenic diet (KD). Metformin has in-vitro anti-cancer activity, through AMPK activation and mTOR inhibition. We hypothesized that the metabolic stress induced by a KD combined with metformin would enhance radiation’s efficacy. We sought to assess the tolerability and feasibility of this approach. A single-institution phase I clinical trial. Radiotherapy was either 60 or 35 Gy over 6 or 2 weeks, for newly diagnosed and recurrent gliomas, respectively. The dietary intervention consisted of a Modified Atkins Diet (ModAD) supplemented with medium chain triglycerides (MCT). There were three cohorts: Dietary intervention alone, and dietary intervention combined with low-dose or high-dose metformin; all patients received radiotherapy. Factors associated with blood ketone levels were investigated using a mixed-model analysis. A total of 13 patients were accrued, median age 61 years, of whom six had newly diagnosed and seven with recurrent disease. All completed radiation therapy; five patients stopped the metabolic intervention early. Metformin 850 mg three-times daily was poorly tolerated. There were no serious adverse events. Ketone levels were associated with dietary factors (ketogenic ratio, p

Purpose Diagnosing primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is challenging because it is a clinicopathologic entity that shares characteristics with other lymphomas and lacks pathognomonic features. We sought to investigate the fidelity between a working diagnosis of PMBCL at our institution and the clinicopathologic criteria established within the 2017 World Health Organization (WHO) classification. Patients and Methods Medical records and archived tissue of patients treated for stage I-II PMBCL from 1998 to 2018 were retrospectively reviewed for clinical and pathologic conformity with current WHO criteria. Disease was characterized as definitely PMBCL if all of the following were present: anterior mediastinal mass with or without lymph node involvement, no extranodal disease, B-cell antigen expression, Epstein-Barr virus negativity, and at least one supportive feature: female gender under age 40, bulky primary tumor, CD30 weakly positive, compartmentalizing alveolar fibrosis, lack of surface immunoglobulin expression, and MUM1 or CD23 positivity. Disease without supportive features or other pathologic findings more suggestive of other entities was characterized as equivocal for PMBCL. Lack of an anterior mediastinal mass, presence of distant lymph node involvement or extranodal disease, lack of B-cell antigen expression, or Epstein-Barr virus positivity were characterized as definitely not PMBCL. Clinical management and outcomes were also assessed. Results Of 63 patients treated for presumed stage I-II PMBCL, 58 (92%) met the criteria for PMBCL. The most common reason for a discordant diagnosis was lack of an anterior mediastinal mass (n = 3). Two additional patients were characterized as having disease equivocal for PMBCL. In retrospect, one patient most likely had a mediastinal gray zone lymphoma due to CD15 positivity and another diffuse large B cell, not otherwise specified, at pathologic review. Five-year progression-free and overall survival were 67% (95% confidence interval, 54-77) and 81% (95% confidence interval, 68-89), respectively, for all patients. Conclusion Despite the complexity of the clinicopathologic criteria of PMBCL, most patients (92%) who were treated for stage I-II PMBCL at our institution appear to have been accurately diagnosed.

There is currently a lack of consensus as to what defines exercise and resistance training in the cancer setting and whether current studies comply with exercise guidelines. This study aimed to quantify the available research studies using resistance training exercise interventions in the breast cancer setting for future clinical trial utilization. We systemically reviewed all available resistance exercise studies during and after breast cancer treatment in an attempt to quantify to the prescribed dose and whether regimens aligned with general exercise guidelines to improve functional mobility, body composition, and metabolic function. They were then compared with recommendations set forth by the national committees that create evidence-based exercise guidelines. Fifty studies met the initial criteria, with 35 meeting analysis criteria for evaluation. Fifteen studies evaluated an exercise regimen during cancer treatment, and 20 evaluated a regimen after treatment. The average adherence rates were 84% for all studies. Only 23 studies listed specific exercises used within the protocol. Most exercise regimens relied on open chain movements and machine exercises. Around half of studies met criteria to achieve hypertrophy, and 66% met American College of Sports Medicine exercise guidelines for cancer patients. A minority of breast cancer studies implementing a resistance training exercise regimen prescribed a regimen or specific dose that follows general exercise guidelines. This study highlights a potential deficiency in exercise programs designed for patients with breast cancer, and these findings should be considered in future study design.

We evaluated daily setup reproducibility of deep inspiration breath hold (DIBH) using mega voltage (MV) imaging for left breast cancer radiation therapy. Analysis of 109 left breast cancer patients across UPMC Hillman Cancer Center network treated using DIBH technique with daily MV imaging was done. Patient characteristics, MV imaging procedure used and inter-fraction directional shifts were collected. For the statistical analyses, we separated all patients into 2 groups in each of the following 3 categories; (1) obese (BMI ≥ 30) vs nonobese, (2) mastectomy vs lumpectomy, (3) internal mammary node (IMN) treatment vs no IMN treatment. The group mean inter-fraction directional shifts were as following: (1) 0.7 mm (superior), 0.8 mm (inferior); (2) 0.65 mm (left), 0.64 mm (right); (3) 0.89 mm (anterior), 0.83 mm (posterior). Also, any directional shift ≥ 2 mm, ≥ 3 mm, ≥ 4 mm, ≥ 5 mm, ≥ 10 mm was found to be 52.9%, 37.6%, 30.9%, 21.9%, 3.7% of total fractions, respectively. In the stratified analysis, obese patients had larger directional shifts (p0.05) and highly associated with number of fractions for ≥ 5 mm in any directional shift compared to nonobese patients (29% vs 17%; p = 0.04). DIBH setup for left breast cancer treatment at our large cancer center network was reproducible with any mean directional shifts less than 1.0 mm using MV imaging. Daily imaging would be more beneficial for obese patients compared to nonobese patients.

There is increasing interest in the use of a ketogenic diet for various adult disorders, however, the ability of adults to generate ketones is unknown. Our goal was to challenge the hypothesis that there would be no difference between adults and children regarding their ability to enter ketosis. Methods: Two populations were studied, both treated with identical very low-carbohydrate high-fat diets: a retrospective series of children with epilepsy or/and metabolic disorders (2009–2016) and a prospective clinical trial of adults with glioblastoma. Dietary intake was assessed based upon written food diaries and 24-h dietary recall. Ketogenic ratio was calculated according to [grams of fat consumed]/[grams of carbohydrate and protein consumed]. Ketone levels (β-hydroxybutyrate) were measured in blood and/or urine. Results: A total of 168 encounters amongst 28 individuals were analyzed. Amongst both children and adults, ketone levels correlated with nutritional ketogenic ratio, however, the absolute ketone levels in adults were approximately one quarter of those seen in children. This difference was highly significant in a multivariate linear regression model, p &lt, 0.0001. Conclusions: For diets with comparable ketogenic ratios, adults have lower blood ketone levels than children, consequently, high levels of nutritional ketosis are unobtainable in adults.

Technological advancements in the capabilities of modern smartphones offer tremendous potential to generate big data from small devices that could influence oncologists' decision-making. Here we describe the value of patient-generated health data (PGHD) that can be captured using mobile devices. We comment on the current use of smartphones in oncology clinical research and describe how smartphones will bring big data into the oncology clinic by enabling continuous patient monitoring, information sharing, and personalized clinical decision making in cancer care. Lastly, we describe practical considerations about how we can access and store PGHD in the future, describing how to harness the clinical value of PGHD and comment on the emerging applications for digital biomarkers captured by smartphones.

Purpose Current standard of care for patients with breast cancer with a positive node on sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy is axillary dissection with irradiation of the regional nodes, but it is unknown whether axillary lymph node dissection (ALND) can be safely omitted if complete axillary radiation is delivered instead. Methods and Materials We identified 161 patients found to have a positive sentinel lymph node on SLNB after neoadjuvant chemotherapy for breast cancer between December 2006 and October 2017, who were treated with or without completion ALND. Local, regional, and distant recurrence and overall survival were analyzed using the Kaplan-Meier method. Patient, disease, and treatment factors potentially predictive of each outcome were entered into Cox regression analysis. Results Median follow-up was 28.8 months (range, 2.5-137.0). The 3-year regional control rate did not differ according to extent of axillary surgery (92.6% for SLNB alone vs 96.4% for SLNB with ALND, P = .616). Regional recurrence occurred as part of first recurrence in 9 patients (5.6%). Five patients failed in axillary levels 1 or 2, 6 failed in axillary level 3 or supraclavicular nodes, and 2 failed in internal mammary nodes, with some patients failing in multiple regional nodal areas. Extent of axillary dissection (SLNB only vs SLNB plus ALND) did not predict for disease control or survival. Patients who underwent ALND were significantly more likely to have lymphedema (25.0% vs 9.4%, P = .021). Conclusions Careful selection of patients with a positive sentinel node on SLNB after neoadjuvant chemotherapy for omission of completion ALND in favor of irradiation of the undissected axilla does not compromise local, regional, or distant control or overall survival and results in lower rates of lymphedema.

Multifocal pattern of regression after neoadjuvant chemotherapy has been identified as a risk factor for ipsilateral breast tumor recurrence (IBTR). We aimed to determine the significance of multifocal regression as a predictor of IBTR after neoadjuvant chemotherapy and breast conservation therapy in the modern era.We retrospectively reviewed 346 patients treated between November 2009 and June 2017. Pattern of regression was categorized as pathologic complete response (pCR), unifocal (tumor present as a cohesive mass), limited multifocal (single cells or clusters of cells concentrated in 1 portion of the fibrotic area), or diffuse multifocal (cells spread over entire fibrotic area). IBTR was defined as new ipsilateral invasive or noninvasive breast tumor after breast conservation therapy. Predictive factors were analyzed using Cox regression.Incidence of multifocal regression was 25.7% for the overall cohort and 12.2% for estrogen receptor (ER) negative/progesterone receptor (PR) negative/human epidermal growth factor receptor 2 (HER2) positive, 17.5% for triple-negative, 36.9% for ER+ or PR+/HER2-, and 38.5% for triple-positive (P .001). With a median follow-up of 41.1 months, 4-year IBTR-free survival after pCR or unifocal regression versus multifocal regression was 94.1% versus 90.9% (P = .411). Pattern of regression (P = .010; compared to pCR, hazard ratio [HR] of 11.2 for diffuse multifocal regression, 1.65 for limited multifocal regression, and 3.81 for unifocal regression), phenotype (P = .001; compared to ER+ or PR+/HER2-, HR of 30.67 for ER-/PR-/HER2+, 25.30 for triple-negative, and 1.60 for triple-positive), and lack of nodal pCR (P = .004; HR of 3.78) predicted for IBTR on multivariate Cox regression. On multivariate subset analysis, pattern of regression and lymphovascular space invasion predicted for IBTR in hormone receptor-negative patients, but pattern of regression was not associated with IBTR for hormone receptor-positive patients.Multifocal regression, hormone receptor-negative phenotype, and lack of nodal pCR predict for increased risk of IBTR after neoadjuvant chemotherapy. Although more common in hormone receptor-positive disease, multifocal regression was associated with worse outcome only in hormone receptor-negative patients.

Purpose Underutilization of hypofractionated whole-breast irradiation (HF-WBI) in large-breasted women may be partially explained by concerns about dose heterogeneity. Although modern planning may mitigate this issue, validated dosimetric guidelines are lacking. Our clinical pathway mandates hypofractionation, guided by institutional dosimetric criteria for plan evaluation. We examined acute radiation dermatitis rates with HF-WBI in large-breasted patients when our guidelines are followed and evaluated factors predictive for dermatitis. Methods and Materials Patients with whole-breast clinical target volumes (WB-CTV) of ≥1000 cm3 treated with HF-WBI were reviewed. WB-CTV V105, V107, and V110 were assessed. Our guidelines recommend limiting V105 to Results From 2012 to 2017, 505 breasts in 502 patients were treated with HF-WBI. The median WB-CTV was 1261.3 cm3 (interquartile range [IQR], 1115.3-1510.0). Most plans (99%) delivered 42.56 Gy in 16 fractions. A cavity boost of 10 Gy in 4 fractions was delivered in 99% of plans. Electrons were used in 69% of boost plans. Three-dimensional field-in-field technique was used in 68% of plans and inverse-planned intensity modulated radiation therapy in 32%. The median WB-CTV V105 was 9.7% (IQR, 5.6%-13.3%); the median WB-CTV V107 was 0.8% (IQR, 0.0%-2.5%). The WB-CTV V110 was 0% in 97.4% of plans (median, 0.0%; IQR, 0.0%-0.0%). Grade 1, 2, and 3 dermatitis rates were 55.0%, 40.8%, and 3.4%, respectively. On multivariate analysis, age >64 years (P = .016; odds ratio [OR] 4.0; 95% confidence interval [CI], 1.3-12.3), WB-CTV >1500 cm3 (P = .006; OR, 4.3; 95% CI, 1.5-12.3), body mass index ≥34 (P = .044; OR, 3.9; 95% CI, 1.0-14.5), and WB-CTV V105 >10% (P = .011; OR, 5.3; 95% CI, 1.5-19.3) predicted for grade 3 dermatitis. Conclusions With our institutional dosimetric guidelines, grade 3 dermatitis rates with HF-WBI in large-breasted women was

Purpose: The machine learning–based automated treatment planning (MLAP) tool has been developed and evaluated for breast radiation therapy planning at our institution. We implemented MLAP for patient treatment and assessed our clinical experience for its performance. Methods and Materials: A total of 102 patients of breast or chest wall treatment plans were prospectively evaluated with institutional review board approval. A human planner executed MLAP to create an auto-plan via automation of fluence maps generation. If judged necessary, a planner further fine-tuned the fluence maps to reach a final plan. Planners recorded the time required for auto-planning and manual modification. Target (ie, breast or chest wall and nodes) coverage and dose homogeneity were compared between the auto-plan and final plan. Results: Cases without nodes (n = 71) showed negligible (

Background Obesity and low muscle mass are associated with worse outcomes of breast cancer patients. We conducted a controlled trial to study the impact of a ketogenic diet (KD) based on natural foods versus an unspecified standard diet (SD) on body composition in breast cancer patients undergoing radiotherapy. Methods Patients with non-metastasized breast cancer were allocated to either the KD (N = 32) or the SD (N = 31) during radiotherapy. Body composition was measured weekly by bioimpedance analysis. Blood parameters and quality of life were assessed before, during, and at the end of radiotherapy. Results A total of 29 KD and 30 SD patients completed the study. During radiotherapy, mean and median fasting BHB concentrations in the KD group were 0.72 and 0.49 mmol/l (range 0.06–4.9) which was significantly higher than those in the SD group (p −16). There was a very small and insignificant increase in body weight and fat mass in the SD group, as well as a decrease of fat free mass. In contrast, patients in the KD group lost body weight and fat free and skeletal muscle mass quickly after diet onset, which for the most part was related to water losses. The KD did not cause further substantial changes in fat free or skeletal muscle mass, but was associated with a gradual decrease of 0.4 kg body weight and fat mass per week (p p = 6.3 × 10−5). Global quality of life remained stable in the SD group but increased in the KD group from a score of 66.7 to 75.0 (p = 0.20). Conclusions In breast cancer patients undergoing curative radiotherapy, a KD based on natural foods is feasible. After initial water losses, the KD tends to reduce body weight and fat mass while preserving fat free and skeletal muscle mass. Trial registration ClinicalTrials.gov identifier: NCT02516501, registered on August 06, 2015.

Background: Osteolytic lesions are present in 75% of patients with multiple myeloma (MM) and frequently require palliation with radiation therapy (RT). Prior case series of patients with MM with bone pain undergoing palliative RT suggests doses ≥12 Gy (equivalent dose in 2Gy fractions, EQD2) provide excellent bone pain relief. However, recent advances in care and novel biologic agents have significantly improved overall survival and quality of life for patients with MM. We hypothesized that lower-dose RT (LDRT, EQD2

Purpose Regional nodal irradiation (RNI) improved disease-free survival by 3% to 5% in 2 large randomized trials, but this small absolute advantage relies on accurate contouring and dose delivery. We audited our network to determine compliance on regional nodal coverage, contouring, and dosimetric parameters with respect to accepted guidelines. Methods and Materials In our network, we have established a clinical pathway for patients with node-positive breast cancer that guides indications for RNI and dosimetric goals. We reviewed records of 183 patients with nodal macrometastases after upfront surgery or involved nodes of any size after neoadjuvant chemotherapy. Radiation treatment plans were examined to determine lymph node volumes treated, whether nodes were contoured, quality of nodal contours, and whether target coverage and normal organ dosimetric constraints were met when RNI was delivered. Results Despite the presence of macrometastases on sentinel lymph node biopsy, no lymph nodes were treated in 2.2% (4 of 183). Of 179 patients who received nodal irradiation, 18 received radiation to axillary levels 1 and 2 only, and 161 patients received RNI. Overall, regional nodes were not treated despite strong indications in 7.6% (14 of 183). Treated nodes were not contoured for 2.2% (4 of 179), and lymph node contours were unacceptable in 15.4% (27 of 175). Of patients receiving RNI, 14.9% (24 of 161) did not have adequate nodal target volume coverage, mean heart dose was >4 Gy for 3.1% (5 of 161), and lung V20 Gy was >35% for 8.7% (14 of 161). Conclusions Adherence to indications for regional nodal treatment was high, but nodes were either not contoured or had unacceptable contour quality in 18% of plans, and coverage was inadequate in 15%. Because the small disease-free survival advantage seen in trials may be decreased with these deviations, routine clinical practice requires detailed peer review to fully translate results of clinical trials.

In our manuscript, we present the food choices available at vending machines in government-run Veterans Affairs Hospitals. The data in this article includes both a quantification of the beverages and packages foods available, along with a comparison of recommendations and sugar content to the government-issued USDA Dietary Guidelines 2015–2020. For further discussion on the results of this study, refer to the full manuscript “Lead by Poor Example: An Assessment of Snacks, Soda, and Junk Food Availability in Veterans Affairs Hospitals” (Champ et al., 2018) [1] .

INTRODUCTION A growing body of preclinical data suggests that statins may exert potent antitumor effects, yet the interactions of these medications with standard therapies and clinical outcomes in this population is less clear. We assessed the impact of statin use on outcomes in patients with advanced-stage pancreatic adenocarcinoma undergoing various treatments. MATERIALS AND METHODS After institutional review board approval, we conducted a retrospective-cohort study consisting of 303 newly diagnosed advanced-stage pancreatic adenocarcinoma patients to determine the impact of statin use on outcomes. Univariate and multivariable Cox proportional hazard regression models were utilized to estimate hazard ratios (HRs). Time-to-event was estimated using Kaplan-Meier survival analysis for overall survival, distant metastasis, and locoregional failure. Baseline and active statin usage were assessed and to mitigate risk of immortal time bias, subanalysis excluding patients with under 6 months of follow-up was conducted. RESULTS Both prior (P=0.021) and active (P=0.030) statin usage correlated with improved survival in this cohort. Surgery, chemoradiation, and statin use improved 2-year survival rates (84.1% vs. 55.0%; P

Purpose Accurate evaluation of patients' health status is a key component of the workup, treatment, and follow-up of cancer patients. Assessments by clinicians (eg, performance status, toxicity grade) and patients (eg, quality of life) play a critical role in current practice but have significant limitations. Technological advances now provide an opportunity to track a new class of objective measures of patient activity, such as daily step counts. Here, we describe recent efforts to incorporate this technology into the field of oncology. Design We conducted a structured literature search using MEDLINE electronic database to identify published observational studies of tracking steps in cancer patients and trials of exercise programs for cancer survivors incorporating pedometers until February 2016. Results Data indicate that physical activity information may supplant existing scales for the assessment of cancer patients' functional capacity. Conclusion Objective activity monitoring is poised to revolutionize the way health care providers assess cancer patients at the time of diagnosis, during treatment, and in the survivorship setting.

Purpose The American College of Surgeons Oncology Group trial Z0011 demonstrated that axillary node dissection (ALND) can be omitted in patients managed with breast conserving surgery and 1 to 2 positive sentinel lymph nodes (SLNs) without adverse effects on locoregional recurrence or disease-free survival (DFS). We investigated patients with breast cancer for whom clinicopathologic features were underrepresented in the Z0011 trial and analyzed radiation therapy treatment patterns and clinical outcomes. Methods and materials We retrospectively reviewed records of patients who underwent a lumpectomy and SLN biopsy with positive SLNs but not an ALND and completed adjuvant radiation therapy. Eligible patients had T3 tumors, >2 positive SLNs, invasive lobular carcinoma, estrogen receptor negative status, extranodal extension, Nottingham Grade 3, or were age Results We identified 105 women treated between July 2011 and July 2016 with a median follow-up time of 48.5 months (Range, 11-83 months). There were 40 women with an extranodal extension (38.9%) and 42 women with grade 3 disease (40.0%). Nineteen patients received whole breast irradiation alone (18.1%) and 86 patients were treated with modified tangent fields including the superior axilla level I/II (81.9%). Thirty-three patients (31.4%) also received a 3rd supraclavicular, nodal-directed field. Among the 86 patients who received axillary nodal irradiation, nodal volume contouring was performed in 77 patients (89.5%). Fifty-one patients (48.6%) also received adjuvant chemotherapy. The overall rates of 4-year DFS and locoregional control (LRC) were 94.3% and 98.1%, respectively. Off all patients, 1 patient experienced an internal mammary nodal recurrence, another patient a contralateral breast tumor, and two patients distant metastases. There were no axillary or ipsilateral breast tumor recurrences. Conclusions This retrospective analysis of women who were underrepresented or excluded from the Z11 trial and underwent a lumpectomy and SLN biopsy with positive SLNs demonstrated comparable rates of LRC and DFS. The high rates of LRC and DFS suggest that completion ALND may be safely omitted in this patient population but larger data sets and longer follow-up times are needed to confirm this finding.

Background: Food recommendations to improve cancer prevention are generally based on epidemiologic data and remain inconsistent. These epidemiologic studies, while controversial, have generally produced results that caution against the consumption of high-fat foods, including eggs, red meat, and full-fat dairy, such as butter and cheese. Yet, limited data exist assessing the quality of individual sources of these foods and the effect each has after its consumption. This study set out to assess the impact sources of food within the same groups from animals raised differently on variables associated with health in human studies. Methods and Materials: A search was conducted through MEDLINE, Embase, and PubMed. In total, twenty-nine studies met inclusion criteria, measuring physiologic changes in humans after consuming animal products following animal diet manipulation. A meta-analysis was attempted to assess the differences between the cohorts in these studies, but was aborted due to poor study quality, vast differences in study design, and a limited number of studies. Results: Studies varied by animal, animal diet manipulation, food product, and overall design. Significant differences were present between groups eating the same food (cheese, beef, eggs, and butter) from animals raised differently, including levels of: conjugated linoleic acid, omega-3 fatty acids (alpha linoleic acid [ALA], docosahexaenoic acid [DHA], and eicosapentaenoic acid [EPA]), and inflammatory factors (triacyl glycerol [TAG], interleukin-6 [IL-6], interleukin-8 [IL-8], tumor necrosis factor [TNF], and C-reactive protein [CRP]). Lipid levels were minimally affected. Conclusions: This work highlights differences in human health markers after consumption of the same foods from animals raised differently. Overall, lipid levels remained relatively neutral, but significant changes in inflammatory and other serum markers and phospholipids were present. Future studies and dietary recommendations should consider how animals are raised, as this can produce different effects on health markers.

Radiation therapy (RT) is often delivered after lumpectomy for women with breast cancer. A common perceived side effect of RT is fatigue, yet its exact effect on activity levels and sleep is unknown. In this study we analyzed the change in activity levels and sleep using an activity tracking device before, during, and after RT for women with early stage breast cancer and ductal carcinoma in situ who underwent adjuvant RT.After institutional review board approval, activity levels were quantified before, during, and after RT with measurements of steps, miles walked, calories burned, and sleep metrics in 10 women fitted with activity trackers. All data were uploaded and tabulated on a secure database. Multivariable linear regressions were used to evaluate changes in these variables over time during the RT course.Median step count was 5047 per day (range, 2741-15,508) and distance traveled was 1.6 miles per day (range, 0.9-5.3). Step count, distance, and calories decreased by an average of 54 steps per day, 0.02 miles per day, and 3 calories per day (median calories 1822; range, 1461-2712) during RT, respectively. These changes were statistically significant (P .001), but not clinically relevant. There was no significant change in sleep (average 6.8 hours per night; range, 5.5-8.3).RT has a minimal effect on activity or sleep in women undergoing treatment for breast cancer. Activity levels varied greatly between patients in a population of women undergoing hypofractionated RT. Because increased activity levels correlate with improved outcomes, further studies evaluating attempts to increase physical activity during as well as after treatment with radiation are warranted.

Background Studies demonstrate safety of omitting axillary nodal dissection for early-stage breast cancer with positive sentinel lymph node (+SLN) biopsy, although trial designs differed in radiation therapy (RT) fields. Regional nodal irradiation was separately shown to improve outcomes in high-risk patients. This led to lack of consensus in RT volumes. Clinical pathways (CPs) standardize care where practice varies unnecessarily. We evaluated the impact of changes to a CP guiding postoperative RT in women with +SLNs on practice patterns throughout a network. Methods and materials We implemented a CP for management of breast cancer with postoperative RT designed to promote uniform nodal treatment. The CP recommended modified tangents (MTs) including level I/II nodes for women with micrometastases (pN1mi). For women with macrometastases (pN1a), CPs recommended including level I/II LN in MT and a third supraclavicular node (SCN) LN ± internal mammary nodes for women with adverse factors present. Results RT fields of 233 women undergoing breast-conserving surgery with +SLN but not axillary nodal dissection were retrospectively reviewed: 25% had pN1mi disease and 75% pN1a. Of 127 women treated before CP changes, 35% with pN1mi and 22% with pN1a were treated with whole-breast irradiation alone. Following CP changes, 106 women were treated: 5% with whole-breast irradiation alone, 58% with MT, and 38% with MT + SCN field. Utilization of MT was associated with CP changes. Utilization of a third SCN field was associated with CP changes, pN stage, extracapsular extension, and total number of adverse factors. Conclusions CPs translate published data and institutional experience into management plans that promote evidence-based care and eliminate unnecessary practice variations. Recognizing that postoperative RT treatment volumes were heterogeneous, we modified the CP based upon the latest evidence for regional nodal irradiation, after which we found increased compliance and consistency with quality guidelines, which will also aid in tracking outcomes in future investigations.

Purpose: Our purpose was to describe preliminary dosimetric and clinical results of a recumbent total skin electron beam therapy (TSEBT) technique and compare this to a conventional standing TSEBT technique. Methods and Materials: A customized treatment platform with recessed side wheels was constructed and commissioned for patients to be treated in a recumbent position. Dosimetric and clinical information was collected for patients treated with this new recumbent technique in addition to that of a cohort of patients treated contemporaneously using the conventional standing method. Dose delivery and clinical outcomes were compared for patients treated with the recumbent and standing techniques. Results: Between 2017 and 2019, 27 patients were treated with TSEBT with the recumbent (n = 13) or conventional standing technique (n = 14) at our institution. Measured dose at 15 body sites could be directly compared. Of these, 10 showed no significant difference between the two techniques while five sites showed significant differences in median measured dose, including the top of left shoulder, right biceps, bend of left elbow, upper back, and medial right thigh (P < .003). Measured dose was significantly higher with the standing technique at these sites with the exception of the upper back. Rates of complete response (25% vs 23%), partial response (50% vs 69%), and stable disease (17% vs 8%) were similar between the standing and recumbent cohorts, respectively (P = .78). Conclusions: We have developed, commissioned, and implemented a floor-based, recumbent technique that allows for treatment of patients who would otherwise not be eligible for TSEBT. Dosimetric and clinical measurements suggest that this technique is a viable alternative to the standing method.

INTRODUCTION Studies have consistently identified an increased risk of pancreatic cancer in diabetics, yet the role hyperglycemia may play in predicting prognosis is less clear. This work aims to evaluate the impact of glycemic state and antidiabetics on outcomes after systemic and local treatment for locoregionally advanced pancreatic cancer. MATERIALS AND METHODS This retrospective study consisted of 303 patients with newly diagnosed advanced-stage pancreatic cancer treated from 2004 to 2014. Kaplan-Meier survival analysis method was used to estimate time to event for overall survival, distant metastasis, and locoregional control. Blood glucose values (n=8599) were assessed both as continuous and categorical variables in univariate and multivariable Cox proportional hazard regression models to estimate hazard ratios (HRs) and identify independent prognostic factors. A 6-month conditional landmark analysis excluding patients with

Over the past decade, significant data have shown that obese men experience a survival detriment after treatment for prostate cancer. While methods to combat obesity are of utmost importance for the prostate cancer patient, newer data reveal the overall metabolic improvements that accompany increased activity levels and intense exercise beyond weight loss. Along these lines, a plethora of data have shown improvement in prostate cancer-specific outcomes after treatment accompanied with these activity levels. This review discusses the metabolic mechanisms in which increased activity levels and exercise can help improve both outcomes for men treated for prostate cancer while lowering the side effects of treatment.

203 Background: Previous studies have demonstrated an association between body mass index (BMI) and survival after breast cancer diagnosis, but the direction and strength of this relationship is inconsistent. Comorbidities that are more common in patients who are obese (BMI≥30) – including diabetes (DM), hypertension (HTN), and hyperlipidemia (HLD) – are often conflated with obesity with regard to their effects on breast cancer outcomes. We sought to determine the effect of BMI on overall survival (OS) among women with breast cancer after controlling for obesity-associated conditions. Methods: Women≥18y diagnosed with stage 0-IV breast cancer at an academic institution from Jan 2014-Jul 2016 and with known BMI at diagnosis were identified. χ2 and ANOVA tests were used to compare intergroup differences. BMI was categorized as normal (

Objectives Calorie restriction (CR) >20% has been hypothesized to aid cancer prevention and treatment. Yet, to our knowledge, there is a lack of reported studies in humans describing tolerance, adherence, or efficacy, and unpublished and incomplete dietary studies may indicate lack of tolerability and compliance. The aim of this study was to assess registered clinical trials using CR for cancer treatment and prevention, rates of completion, and published reports to determine whether barriers to publication may be indicative of either negative studies, or incompletion due to unreported compliance issues. Methods Current registered clinical trials assessing CR in cancer prevention and treatment were assessed at clinicaltrials.gov and the International Clinical Trials Registry at the World Health Organization. Assessment of study completion and publication was calculated and compared with methods of CR used, as were rates of inactive and incomplete studies, dormant studies, time of dormancy, type of study, and generalizable conclusions. Results Twenty-nine trials were registered assessing CR in cancer treatment or prevention. Of these studies, 18 met initial criteria, and only 4 had completed and published results. Three of these tested a CR regimen incorporating exercise or intermittent restriction. Target CR ranged from 500 to 1000 kcal/d, with one study aim of 20% CR; no study reported rates of actual calorie intake. The majority of dormant and unpublished studies (69%) used general dietary CR and was without update ranging from 265 to 2518 d. Only one study reported on the side effects of the CR regimen; compliance and adherence to the regimen was described in the four completed studies that reported results. Only two studies were registered as pilot studies testing the feasibility of CR. Conclusions Poor completion and lack of reporting of results is apparent in the majority of studies assessing CR for cancer prevention or treatment. These findings should be considered during the design of future studies assessing dietary strategies for cancer prevention or treatment.

IMPORTANCE: Observational data linking physical activity and exercise exposure with either reduced risk or progression of cancer has fueled interest in the initiation of large-scale definitive trials to test the effects of exercise therapy on disease outcomes. However, several major knowledge gaps impede the rational and optimal design of such trials. OBSERVATIONS: Critical prerequisites underpinning the success of several recent contemporary anticancer agents have included adequate demonstration of antitumor activity (in phase 1/2 trials) as well as identification of essential prerequisites (e.g., biologically effective dose, predictors of response) permitting optimal design of definitive trials. The existing evidence base investigating exercise as a candidate anticancer preventive or treatment strategy is predominantly confined to observational data – data with several inherent limitations. Consequently, the antitumor activity of exercise remains unclear and perhaps more importantly, such data is not sufficient to accurately derive the dose, prescription regimen, or patients most likely to benefit from exercise. In adherence with translational frameworks for lifestyle therapy development, we highlight the urgent need for early phase 1/2-equivalent trials to fill current knowledge gaps to optimize the development and potential efficacy of exercise therapy. CONCLUSIONS AND RELEVANCE: Exercise therapy has significant promise to be a highly efficacious, low-toxicity, and cost-effective therapy to improve cancer outcomes. However, the majority of non-traditional therapies in cancer prevention and prognosis fail in definitive trials. We contend these failures provide critical lessons for the continued development of exercise as a candidate anticancer therapy.

Objective The Veterans Health Administration is the largest integrated health care system fully funded through the US government; however, compliance with government dietary recommendations within Veterans Affairs (VA) hospitals is not well known. The aim of this study was to determine which foods are available at VA hospitals and whether these foods comply with government recommendations. Methods Process verification for a Freedom of Information Act request was used to assess government-run inpatient and outpatient VA hospital facilities by accessing the location, quantity, and contents of vending machines. These foods and beverages were then quantified and compared with the US Department of Agriculture Dietary Guidelines for Americans 2015-2020 (eighth edition). Results Of the beverages supplied, 49% contained >55 g of sugar, supplying >10% of daily calories in added sugar in a single serving. Of all beverages, 50% contained >50 g of added sugar (range 17-77 g per bottle/can). The 65 available food items were comprised of 28% candy, 14% potato chips/puffed corn snacks, 11% pastries/frosted baked goods, 11% crackles/pretzels, and 8% nuts/trail mix, and the remainder consisted of jerky, pork rinds, gum, and popcorn. Nuts/trail mix and granola-items meeting nutritional guidelines-comprised five and three options in total, respectfully. Conclusions All VA Hospitals contain vending machines providing a majority of soda, candy, and junk foods that directly conflict with healthy food choice recommendations from US governing health bodies. Few sources meeting US dietary guidelines are available in vending machines at these government-run facilities, which serve as poor examples for patients who are attempting to follow a healthy diet.

Introduction: Epidemiologic data indicate diabetes confers an augmented risk of lung cancer development, yet the relationship between hyperglycemia, metabolic agents, and prognosis is unclear. We analyzed the impact of hyperglycemia, anti-diabetic agents, and statins on outcomes in non-small cell lung cancer (NSCLC) patients undergoing chemoradiation. Method and Materials: In total, data from 170 patients with stage III NSCLC treated at the University of Pittsburgh Medical Center between 2001 and 2014 were obtained for analysis. Kaplan-Meier survival analysis was used to estimate time-to-event for overall survival (OS), disease-free survival, distant metastasis (DM), and loco-regional control (LRC). Blood glucose values (n = 2870), statins, and diabetic medications were assessed both continuously and categorically in univariable and multivariable Cox proportional hazard regression models to estimate hazard ratios and identify prognostic factors. Results: Tumor volume was a negative prognostic factor for OS, disease-free survival, DM, and LRC (p = 0.001). Tumor stage and treatment time were associated with increased all-cause mortality. Any glucose measurement ≥ 130 mg/dl during treatment (2-year estimate 49.9 vs. 65.8%, p = 0.095) was borderline significant for decreased LRC, with similar trends on multivariable analysis (HR 1.636, p = 0.126) and for OS (HR 1.476, p = 0.130). Statin usage was associated with improved 2-year LRC (53.4 vs. 62.4%, p = 0.088) but not with improvements in survival. Other glycemic parameters, comorbid diabetes diagnosis, or anti-diabetic medications were not significantly associated with outcomes. Conclusions: There were trends for blood glucose value over 130 mg/dl and statin nonuse being associated with inferior prognosis for LRC in stage III NSCLC patients; glycemic state, statin usage, and glucose-modulating medications were not associated with survival outcomes in multivariable analysis in this retrospective database.

Background Ketogenic therapy in the form of ketogenic diets or calorie restriction has been proposed as a metabolic treatment of high grade glioma (HGG) brain tumors based on mechanistic reasoning obtained mainly from animal experiments. Given the paucity of clinical studies of this relatively new approach, our goal is to extrapolate evidence from the greater number of animal studies and synthesize it with the available human data in order to estimate the expected effects of ketogenic therapy on survival in HGG patients. At the same time we are using this analysis as an example for demonstrating how Bayesianism can be applied in the spirit of a circular view of evidence. Results A Bayesian hierarchical model was developed. Data from three human cohort studies and 17 animal experiments were included to estimate the effects of four ketogenic interventions (calorie restriction/ketogenic diets as monotherapy/combination therapy) on the restricted mean survival time ratio in humans using various assumptions for the relationships between humans, rats and mice. The impact of different biological assumptions about the relevance of animal data for humans as well as external information based on mechanistic reasoning or case studies was evaluated by specifying appropriate priors. We provide statistical and philosophical arguments for why our approach is an improvement over existing (frequentist) methods for evidence synthesis as it is able to utilize evidence from a variety of sources. Depending on the prior assumptions, a 30–70% restricted mean survival time prolongation in HGG patients was predicted by the models. The highest probability of a benefit (> 90%) for all four ketogenic interventions was obtained when adopting an enthusiastic prior based on previous case reports together with assuming synergism between ketogenic therapies with other forms of treatment. Combinations with other treatments were generally found more effective than ketogenic monotherapy. Conclusions Combining evidence from both human and animal studies is statistically possible using a Bayesian approach. We found an overall survival-prolonging effect of ketogenic therapy in HGG patients. Our approach is best compatible with a circular instead of hierarchical view of evidence and easy to update once more data become available. Electronic supplementary material The online version of this article (10.1186/s12976-018-0084-y) contains supplementary material, which is available to authorized users.