Incidence and imaging characteristics of difficult to detect retrospectively identified brain metastases in patients receiving repeat courses of stereotactic radiosurgery.

PURPOSE: During stereotactic radiosurgery (SRS) planning for brain metastases (BM), brain MRIs are reviewed to select appropriate targets based on radiographic characteristics. Some BM are difficult to detect and/or definitively identify and may go untreated initially, only to become apparent on future imaging. We hypothesized that in patients receiving multiple courses of SRS, reviewing the initial planning MRI would reveal early evidence of lesions that developed into metastases requiring SRS. METHODS: Patients undergoing two or more courses of SRS to BM within 6 months between 2016 and 2018 were included in this single-institution, retrospective study. Brain MRIs from the initial course were reviewed for lesions at the same location as subsequently treated metastases; if present, this lesion was classified as a "retrospectively identified metastasis" or RIM. RIMs were subcategorized as meeting or not meeting diagnostic imaging criteria for BM (+ DC or -DC, respectively). RESULTS: Among 683 patients undergoing 923 SRS courses, 98 patients met inclusion criteria. There were 115 repeat courses of SRS, with 345 treated metastases in the subsequent course, 128 of which were associated with RIMs found in a prior MRI. 58% of RIMs were + DC. 17 (15%) of subsequent courses consisted solely of metastases associated with + DC RIMs. CONCLUSION: Radiographic evidence of brain metastases requiring future treatment was occasionally present on brain MRIs from prior SRS treatments. Most RIMs were + DC, and some subsequent SRS courses treated only + DC RIMs. These findings suggest enhanced BM detection might enable earlier treatment and reduce the need for additional SRS.

Time from biopsy to radical prostatectomy by race in an equal-access healthcare system: Results from the SEARCH cohort.

BACKGROUND: We previously showed that within an equal-access health system, race was not associated with the time between prostate cancer (PC) diagnosis and radical prostatectomy (RP). However, in the more recent time-period of the study (2003-2007), Black men had significantly longer times to RP. We sought to revisit the question in a larger study population with more contemporary patients. We hypothesized that time from diagnosis to treatment would not differ by race, even after accounting for active surveillance (AS) and the exclusion of men at very low to low risk of PC progression. METHODS: We analyzed data from 5885 men undergoing RP from 1988 to 2017 at eight Veterans Affairs Hospitals from SEARCH. Multiple linear regression was used to compare time from biopsy to RP and to examine the risk of delays (>90 and >180 days) between races. In sensitivity analyses we excluded men deemed to have initially chosen AS based on having >365 days from biopsy to RP and men at very low to low PC risk for progression according to National Comprehensive Cancer Network Clinical Practice Guidelines. RESULTS: At biopsy, Black men (n = 1959) were younger, had lower body mass index, and higher prostate specific antigen levels, (all p < 0.02), compared to White men (n = 3926). Time from biopsy to RP was longer in Black men (mean days: 98 vs. 92; adjusted ratio of mean number of days, 1.07 [95% confidence interval: 1.03-1.11], p < 0.001); however, there were no differences in delays >90 or >180 days after adjusting for confounders (all p ≥ 0.286). Results were similar following the exclusion of men potentially under on AS and at very low and low risk. CONCLUSIONS: In an equal-access healthcare system, we did not find evidence of clinically relevant differences in time from biopsy to RP in Black versus White men.

Are higher pre-diagnosis follicle stimulating hormone levels associated with long-term prostate cancer risk?

BACKGROUND: Follicle stimulating hormone (FSH) is a pituitary hormone that helps regulate testosterone homeostasis. Although it is generally accepted that FSH levels increase with LHRH-agonist therapy for prostate cancer (PC), the specific impact of FSH levels on risk of PC diagnosis is largely unknown. The objective of this study was to perform a population-level analysis to assess the association between FSH levels and PC diagnosis. METHODS: All men (n = 386,018) who had a pre-PC diagnosis FSH level and complete data were identified within the Veterans Affairs Health System between 1999 and 2018. The association between FSH level and time from FSH test to PC diagnosis was tested using stratified Cox proportional hazards models. Multivariable models were adjusted for age, year, race, body mass index, and Charlson comorbidity index. Due to nonproportional hazards over time, time to PC was modeled separately: ≤4 years after an FSH test and >4 years following an FSH test. RESULTS: Median age at first FSH level was 64 years (interquartile range [IQR]: 54-72), median year of FSH was 2010 (IQR: 2005-2014), and 70% of the cohort was white. Median follow-up was 76 months (IQR: 38-126) during which 17,519 men (4.5%) were diagnosed with PC. On multivariable analysis, in the first 4 years after FSH test, there was no association between FSH and time to PC diagnosis. Starting from 4 years after FSH test, on multivariable analysis, a higher FSH level was associated with lower risk of PC with continuous modeling, but found no association with log continuous and categorical modeling. CONCLUSIONS: In this population-level study among male veterans receiving an FSH test for an unknown clinical indication, associations between FSH levels and PC risk were inconsistent and likely driven by selection bias and confounding variables. Future studies should consider different study designs.

Prostate weight and prostate cancer outcomes after radical prostatectomy: Results from the SEARCH cohort study.

BACKGROUND: Smaller prostates have been linked to unfavorable clinical characteristics and poor short-term outcomes following radical prostatectomy (RP). We examined the relation between prostate weight at RP and prostate cancer (PC) outcomes post-RP. METHODS: Men in the SEARCH cohort undergoing RP between 1988 and 2017 (N = 6242) were studied for PC-specific mortality (PCSM) as the primary outcome, and for biochemical recurrence (BCR), castration-resistant PC (CRPC) and metastasis as secondary outcomes. Hazard ratios (HR) and 95% confidence intervals (CI) were determined for associations between prostate weight and outcomes using Fine-Gray competing risk regression multivariable analyses. Sensitivity analyses were also carried out following exclusion of: (i) men with extreme prostate weights (<20 g and ≥100 g); and (ii) men with elevated prostate specific antigen (PSA) levels. RESULTS: Median values for age, pre-RP PSA and prostate weight were 63 years, 6.6 ng/ml, and 42.0 g, respectively. During a median follow-up of 7.9 years, 153 (3%) died from PC, 2103 (34%) had BCR, 203 (3%) developed CRPC, and 289 (5%) developed metastases. Prostate weight was not associated with PCSM in the main analyses (multivariable HR = 1.43; 95% CI: 0.87-2.34) or in sensitivity analyses. Prostate weight was inversely associated with BCR in the main analyses (multivariable HR = 0.70; 95%CI: 0.61-0.79) which was unchanged in sensitivity analyses. HRs for prostate weight and CRPC and metastasis were elevated but statistical significance was not attained. Similar results were observed in sensitivity analyses. CONCLUSIONS: Inconsistent results for prostate weight and short-term vs longer-term outcomes highlight the need to better understand the complex biology leading to prostate size and the relevance of prostate size as a predictor of PC outcomes.

The influence of low-carbohydrate diets on the metabolic response to androgen-deprivation therapy in prostate cancer.

BACKGROUND: Prostate cancer (PC) is the second most lethal cancer for men. For metastatic PC, standard first-line treatment is androgen deprivation therapy (ADT). While effective, ADT has many metabolic side effects. Previously, we found in serum metabolome analysis that ADT reduced androsterone sulfate, 3-hydroxybutyric acid, acyl-carnitines but increased serum glucose. Since ADT reduced ketogenesis, we speculate that low-carbohydrate diets (LCD) may reverse many ADT-induced metabolic abnormalities in animals and humans. METHODS: In a multicenter trial of patients with PC initiating ADT randomized to no diet change (control) or LCD, we previously showed that LCD intervention led to significant weight loss, reduced fat mass, improved insulin resistance, and lipid profiles. To determine whether and how LCD affects ADT-induced metabolic changes, we analyzed serum metabolites after 3-, and 6-months of ADT on LCD versus control. RESULTS: We found androsterone sulfate was most consistently reduced by ADT and was slightly further reduced in the LCD arm. Contrastingly, LCD intervention increased 3-hydroxybutyric acid and various acyl-carnitines, counteracting their reduction during ADT. LCD also reversed the ADT-reduced lactic acid, alanine, and S-adenosyl methionine (SAM), elevating glycolysis metabolites and alanine. While the degree of androsterone reduction by ADT was strongly correlated with glucose and indole-3-carboxaldehyde, LCD disrupted such correlations. CONCLUSIONS: Together, LCD intervention significantly reversed many ADT-induced metabolic changes while slightly enhancing androgen reduction. Future research is needed to confirm these findings and determine whether LCD can mitigate ADT-linked comorbidities and possibly delaying disease progression by further lowering androgens.

Severe Hypocalcemia After Thyroidectomy: An Analysis of 7366 Patients.

OBJECTIVE: The aim of the study was to determine severe hypocalcemia rate following thyroidectomy and factors associated with its occurrence. BACKGROUND: Hypocalcemia is the most common complication after thyroidectomy. Severe post-thyroidectomy hypocalcemia can be life-threatening; data on this specific complication are scarce. METHODS: Patients who underwent thyroidectomy in the American College of Surgeons-National Surgical Quality Improvement Program thyroidectomy-targeted database (2016-2017) were abstracted. A severe hypocalcemic event was defined as hypocalcemia requiring intravenous calcium, emergent clinic/hospital visit, or a readmission for hypocalcemia. Multivariable regression was used to identify factors independently associated with occurrence of severe hypocalcemia. RESULTS: Severe hypocalcemia occurred in 5.8% (n = 428) of 7366 thyroidectomy patients, with 83.2% necessitating intravenous calcium treatment. Rate of severe hypocalcemia varied by diagnosis and procedure (0.5% for subtotal thyroidectomy to 12.5% for thyroidectomy involving neck dissections). Overall, 38.3% of severe hypocalcemic events occurred after discharge; in this subset, 59.1% experienced severe hypocalcemia despite being discharged with calcium and vitamin D. Severe hypocalcemia patients had higher rates of recurrent laryngeal nerve injury (13.4% vs 6.6%), unplanned reoperations (4.4% vs 1.3%), and longer hospital stay (30.4% vs 6.2% ≥3 days (all P < 0.01). After multivariate adjustment, severe hypocalcemia was associated with multiple factors including Graves disease [odds ratio (OR) = 2.06], lateral neck dissections (OR: 3.10), and unexpected reoperations (OR = 3.55); all P values less than 0.01. CONCLUSIONS: Severe hypocalcemia and suboptimal hypocalcemia management after thyroidectomy are common. Patients who experienced severe hypocalcemia had higher rates of nerve injury and unexpected reoperations, indicating surgical complexity and provider inexperience. More biochemical surveillance particularly a parathyroid hormone-based protocol, fine-tuned supplementation, and selective referral could reduce occurrence of this morbid complication.

Family history of prostate cancer and prostate tumor aggressiveness in black and non-black men;results from an equal access biopsy study.

PURPOSE: To test for racial differences in associations between family history (FH) of prostate cancer (PC) and prostate cancer aggressiveness in a racially diverse equal access population undergoing prostate biopsy. SUBJECTS/PATIENTS AND METHODS: We prospectively enrolled men undergoing prostate biopsy at the Durham Veterans Administration from 2007 to 2018 and assigned case or control status based on biopsy results. Race and FH of PC were self-reported on questionnaires. Logistic regression was used to test the association between FH and PC diagnosis overall and by tumor aggressiveness [high- (Grade Group 3-5) or low-grade (Grade Group 1-2) vs. no cancer], overall, and stratified by race. Models were adjusted for age and year of consent, race, PSA level, digital rectal exam findings, prostate volume, and previous (negative) biopsy receipt. RESULTS: Of 1,225 men, 323 had a FH of PC and 652 men were diagnosed with PC on biopsy. On multivariable analysis, FH was associated with increased odds of high-grade PC in black (OR 1.85, p = 0.041) and all men (OR 1.56, p = 0.057) and was unrelated to overall or low-grade PC diagnosis, overall, or stratified by race (all p ≥ 0.325). In sensitivity analyses among men without a previous biopsy, results were slightly more pronounced. CONCLUSION: In this setting of equal access to care, positive FH of PC was associated with increased tumor aggressiveness in black men, but not non-black men undergoing prostate biopsy. Further research is required to tease apart the contribution of genetics from increased PC awareness potentially influencing screening and biopsy rates in men with FH.

Monocyte counts and prostate cancer outcomes in white and black men: results from the SEARCH database.

PURPOSE: Circulating inflammatory markers may predict prostate cancer (PC) outcomes. For example, a recent study showed that higher peripheral blood monocyte counts were associated with aggressive PC in Asian men undergoing radical prostatectomy (RP). Herein, we investigated whether peripheral monocyte count can predict long-term PC outcomes after RP in black and white men. METHODS: We retrospectively reviewed data on 2345 men undergoing RP from 2000 to 2017 at eight Veterans Affairs hospitals. Data on monocyte count within 6 and 12 months prior to surgery were collected. The study outcomes were biochemical recurrence (BCR), castration-resistant PC (CRPC), metastasis, all-cause mortality (ACM), and PC-specific morality (PCSM). Cox-proportional hazard models were used to assess the associations between pre-operative monocyte count and the above-mentioned outcomes accounting for confounders. RESULTS: Of 2345 RP patients, 972 (41%) were black and 1373 (59%) were white men. In multivariable analyses, we found no associations between monocyte count and BCR among all men (HR: 1.36, 95%CI 0.90-2.07) or when analyses were stratified by race (HR: 1.30, 95%CI 0.69-2.46, in black men; HR:1.33, 95%CI 0.76-02.33, in white men). Likewise, no overall or race-specific associations were found between monocyte count and CRPC, metastases, ACM, and PCSM, all p ≥ 0.15. Results were similar for monocyte count measured at 12 months prior to RP. CONCLUSION: In black and white PC patients undergoing RP, peripheral monocyte count was not associated with long-term PC outcomes. Contrary to what was found in Asian populations, monocyte count was not associated with PC outcomes in this study.

Association of body composition with odds of breast cancer by molecular subtype: analysis of the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Nigerian Women (MEND) study.

BACKGROUND: The association between obesity and breast cancer (BC) has been extensively studied among US, European and Asian study populations, with often conflicting evidence. However, despite the increasing prevalence of obesity and associated conditions in Africa, the continent with the highest age-standardized BC mortality rate globally, few studies have evaluated this association, and none has examined in relation to molecular subtypes among African women. The current analysis examines the association between body composition, defined by body mass index (BMI), height, and weight, and BC by molecular subtype among African women. METHODS: We estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between measures of body composition and BC and molecular subtypes among 419 histologically confirmed cases of BC and 286 healthy controls from the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Women of Nigerian Descent (MEND) case-control study. RESULTS: Higher BMI (aOR: 0.79; 95% CI: 0.67, 0.95) and weight (aOR: 0.83; 95% CI: 0.69, 0.98) were associated with reduced odds of BC in adjusted models, while height was associated with non-statistically significant increased odds of BC (aOR: 1.07, 95% CI: 0.90, 1.28). In pre/peri-menopausal, but not post-menopausal women, both higher BMI and weight were significantly associated with reduced odds of BC. Further, higher BMI was associated with reduced odds of Luminal A, Luminal B, and HER2-enriched BC among pre/peri-menopausal women, and reduced odds of triple-negative BC among post-menopausal women. CONCLUSIONS: Higher BMI and weight were associated with reduced odds of BC overall and by molecular subtype among West African women. Larger studies of women of African descent are needed to definitively characterize these associations and inform cancer prevention strategies.

Abdominal and pelvic adipose tissue distribution and risk of prostate cancer recurrence after radiation therapy.

BACKGROUND: Fat distribution varies between individuals of similar body mass index (BMI). We hypothesized that visceral obesity is more strongly associated with poor prostate cancer outcomes than overall obesity defined by BMI. MATERIALS AND METHODS: We quantified abdominal visceral and subcutaneous fat area (VFA and SFA), and pelvic periprostatic adipose tissue area (PPAT), using computed tomography scans from radiation-treated prostate cancer patients at the Durham North Carolina Veterans Administration Hospital. Multivariable-adjusted Cox regression examined associations between each adiposity measure and risk of recurrence, overall and stratified by race and receipt of androgen deprivation therapy (ADT). RESULTS: Of 401 patients (59% black) treated from 2005 to 2011, 84 (21%) experienced recurrence during 9.3 years median follow-up. Overall, obesity defined by BMI was not associated with recurrence risk overall or stratified by race or ADT, nor was any measure of fat distribution related to the risk of recurrence overall or by race. However, higher VFA was associated with increased risk of recurrence in men who received radiation only (hazard ratio [HR], 1.79; 95% confidence interval [CI], 0.87-3.66), but inversely associated with recurrence risk in men treated with radiation and ADT (HR, 0.49; 95% CI, 0.24-1.03; P-interaction = .002), though neither association reached statistical significance. Similar patterns of ADT-stratified associations were observed for PPAT and SFA. CONCLUSIONS: Associations between abdominal and pelvic adiposity measures and recurrence risk differed significantly by ADT receipt, with positive directions of association observed only in men not receiving ADT. If confirmed, our findings suggest that obesity may have varying effects on prostate cancer progression risk dependent on the hormonal state of the individual.

Sleep quality and prostate cancer aggressiveness: Results from the REDUCE trial.

BACKGROUND: Disrupted sleep has been associated with increased risk of certain cancers. Little data exist in prostate cancer. We tested the association between sleep quality and prostate cancer diagnosis overall and by tumor grade in the Reduction by Dutasteride of Prostate Cancer Events chemoprevention trial. We hypothesized that worse sleep quality would be associated with increased tumor aggressiveness. METHODS: At baseline, 5614 men completed a validated six-item questionnaire on sleep quality. We generated a composite score categorized into tertiles to measure overall sleep quality and assessed each sleep quality question individually. Logistic regression was used to test associations between baseline sleep quality and overall, low-grade and high-grade prostate cancer diagnosis at 2-year study-mandated biopsy. Models were stratified by nocturia. RESULTS: Overall sleep quality was unrelated to overall or low-grade prostate cancer. Worse overall sleep quality was associated with elevated odds of high-grade prostate cancer (odds ratio [OR]T3vsT1 1.15; 95% confidence interval [CI]: 0.83-1.60 and ORT2vsT1 1.39; 95% CI: 1.01-1.92). Men reporting trouble falling asleep at night sometimes vs never had elevated odds of high-grade prostate cancer (OR: 1.51; 95% CI: 1.08-2.09) while trouble staying awake during the day was associated with decreased odds of low-grade prostate cancer (OR: 0.65; 95% CI: 0.49-0.86). Results were similar within strata of nocturia severity. CONCLUSIONS: Overall, associations between sleep quality and prostate cancer were inconsistent. However, there was some evidence for a positive association between insomnia and high-grade prostate cancer, and an inverse relationship between daytime sleepiness and low-grade prostate cancer; findings that should be validated by future studies.

Obesity, race, and long-term prostate cancer outcomes.

BACKGROUND: The authors previously found that obesity was linked with prostate cancer (PC)-specific mortality (PCSM) among men who underwent radical prostatectomy (RP). Herein, in a larger RP cohort, the authors investigated whether the association between obesity and long-term PC outcomes, including PCSM, differed by race. METHODS: Data from 5929 patients who underwent RP and were in the Shared Equal Access Regional Cancer Hospital (SEARCH) database were analyzed. Prior to RP, body mass index (BMI) was measured and recorded in the medical records. BMI was categorized as normal weight (<25 kg/m2 ), overweight (25-29.9 kg/m2 ), and obese (≥30 kg/m2 ). The authors assessed the association between BMI and biochemical disease recurrence (BCR), castration-resistant prostate cancer (CRPC), metastasis, and PCSM, accounting for confounders. RESULTS: Of the 5929 patients, 1983 (33%) were black, 1321 (22%) were of normal weight, 2605 (44%) were overweight, and 2003 (34%) were obese. Compared with white men, black men were younger; had higher prostate-specific antigen levels; and were more likely to have a BMI ≥30 kg/m2 , seminal vesicle invasion, and positive surgical margins (all P ≤ .032). During a median follow-up of 7.4 years, a total of 1891 patients (32%) developed BCR, 181 patients (3%) developed CRPC, 259 patients (4%) had metastasis, and 135 patients (2%) had died of PC. On multivariable analysis, obesity was found to be associated with an increased risk of PCSM (hazard ratio, 1.78; 95% confidence interval, 1.04-3.04 [P = .035]). No interaction was found between BMI and race in predicting PCSM (P ≥ .88), BCR (P ≥ .81), CRPC (P ≥ .88), or metastasis (P ≥ .60). Neither overweight nor obesity was associated with risk of BCR, CRPC, or metastasis (all P ≥ .18). CONCLUSIONS: Obese men undergoing RP at several Veterans Affairs hospitals were found to be at an increased risk of PCSM, regardless of race.

Recurrent Laryngeal Nerve Injury After Thyroid Surgery: An Analysis of 11,370 Patients.

BACKGROUND: Recurrent laryngeal nerve (RLN) injury is a well-known, potentially serious complication of thyroid surgery. We investigated factors associated with RLN injury during thyroid surgery using a multi-institutional data set. MATERIALS AND METHODS: Patients who underwent either lobectomy or total thyroidectomy were abstracted from the American College of Surgeons National Surgical Quality Improvement Program thyroidectomy-specific database (2016-2017). Baseline and operative factors associated with RLN injury ≤30 d of surgery were analyzed using bivariate and multivariate methods. Secondary complications of interest included unplanned reintubation and hypocalcemia. RESULTS: RLN injury occurred in 6.0% (n = 677) of the 11,370 patients included in the study. The RLN injury rate varied significantly based on the primary indication for surgery, from 4.3% in patients undergoing surgery for a single nodule to 9.0% in patients undergoing surgery for differentiated cancer (P < 0.01). RLN injury occurred more often in thyroidectomies than lobectomies (6.9% versus 4.3%, P < 0.01) and in surgeries without intraoperative nerve monitoring (6.5% versus 5.6%, P = 0.01). After multivariate adjustment, RLN injury was independently associated with age ≥65 y [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.3-2.0], total thyroidectomy (OR = 1.4, 95% CI 1.1-1.6), and diagnosis of thyroid malignancy (OR = 2.1, 95% CI = 1.6-2.7) (all P < 0.001) but not intraoperative RLN monitoring (OR = 0.9, 95% CI = 0.7-1.0, P = 0.06). CONCLUSIONS: In this large multi-institutional study, RLN injury ≤30 d of surgery occurred in nearly 6% of thyroid surgeries. This comprehensive analysis of RLN injury can be used to guide informed consent discussions and aid surgeons in identifying candidates who may be at higher risk for injury.

Implementation of a Surgical Oncology Disparities Curriculum for Preclinical Medical Students.

BACKGROUND: Underinsured and uninsured surgical-oncology patients are at higher risk of perioperative morbidity and mortality. Curricular innovation is needed to train medical students to work with this vulnerable population. We describe the implementation of and early educational outcomes from a student-initiated pilot program aimed at improving medical student insight into health disparities in surgery. MATERIALS/METHODS: First-year medical students participated in a dual didactic and perioperative-liaison experience over a 10-month period. Didactic sessions included surgical-skills training and faculty-led lectures on financial toxicity and management of surgical-oncology patients. Students were partnered with uninsured and Medicaid patients receiving surgical-oncology care and worked with these patients by providing appointment reminders, clarifying perioperative instructions, and accompanying patients to surgery and clinic appointments. Students' interest in surgery and self-reported comfort in 15 Association of American Medical Colleges core competencies were assessed with preparticipation and postparticipation surveys using a 5-point Likert scale. RESULTS: Twenty-four first-year students were paired with 14 surgical-oncology patients during the 2017-2018 academic year. Sixteen students (66.7%) completed both preprogram and postprogram surveys. Five students (31.3%) became "More Interested" in surgery, whereas 11 (68.8%) reported "Similar Interest or No Change." Half of the students (n = 8) felt more prepared for their surgery clerkship after participating. Median self-reported comfort improved in 7/15 competencies including Oral Communication and Ethical Responsibility. All students reported being "Somewhat" or "Extremely Satisfied" with the program. CONCLUSIONS: We demonstrate that an innovative program to expose preclinical medical students to challenges faced by financially and socially vulnerable surgical-oncology patients is feasible and may increase students' clinical preparedness and interest in surgery.

Patterns of response and progression in bone and soft tissue during and after treatment with radium-223 for metastatic castrate-resistant prostate cancer.

BACKGROUND: Radium-223 improves survival and time to first symptomatic skeletal event in symptomatic bone predominant metastatic castrate-resistant prostate cancer (mCRPC). The imaging response to radium-223 has not been well characterized. METHODS: To describe patterns of response and progression with radium-223, we performed a retrospective review of all mCPRC patients who received radium-223 at Duke from 1 June 2013 to 1 June 2015. Radionuclide bone scans obtained at baseline, during, and after treatment were reviewed by two radiologists. The automated bone scan index (aBSI) was generated at each time point using EXINI boneBSI version 2.4. Computed tomography (CT) and magnetic resonance imaging (MRI) clinical radiology reports were reviewed to evaluate for soft tissue, visceral, epidural, and bone progression. Clinical data were abstracted from the electronic health record. RESULTS: We identified 61 men who received at least one dose of radium-223 at Duke during the study period (median, 5 doses; range, 1-6). Among men with imaging during treatment, 2 of 14 (14.3%) had resolution of greater than or equal to 1 lesion on bone scan, 4 of 14 (28.6%) had zero new bone lesions, 10 of 14 (71.4%) had greater than or equal to 1 new bone lesion, 14 of 26 (53.9%) progressed on CT. After radium-223, 6 of 39 (15.4%) had resolution of 1 to 4 bone lesions, 15 of 39 (38.5%) demonstrated zero new bone lesions, 24 of 39 (61.5%) progressed on bone scan, 15 of 37 (40.5%) progressed on CT, and 10 of 34 (29.4%) progressed on both bone scan and CT. No men with zero new bone lesions after radium-223 ultimately progressed in bone alone and only 3 of 15 eventually demonstrated any progression in the bone. aBSI decreased significantly from baseline to after radium-223 among men with zero new bone lesions (median change in aBSI -0.23 [IQR, -1.5, 0.02]) and increased significantly for men with greater than or equal to 1 new postradium bone lesions (median change in aBSI 1.41 [IQR, -0.05, 3.63] [P = 0.018]). CONCLUSIONS: Bone and soft tissue progression during and following radium-223 is common in heavily pretreated men with mCRPC. However, stable disease and responses were observed in a subset of patients and may be associated with durable treatment response in the bone. Prospective studies are needed to further investigate the change in aBSI as a biomarker of bone scan response/stabilization and progression following treatment with radium-223.

Interplay between exercise and BMI; results from an equal access, racially diverse biopsy study.

PURPOSE: It is unclear if exercise and BMI interact to influence prostate cancer (PC) risk. We hypothesized BMI is linked with increased aggressive PC risk but this link will be attenuated with increased exercise. METHODS: Men undergoing prostate biopsy completed a questionnaire and metabolic equivalent (MET) hours of exercise was calculated. Of 695 men, 349 had PC; 161 low-grade, and 188 high-grade. We assessed the link between exercise and PC risk, high-grade PC (Gleason 7-10), and low-grade PC (Gleason 2-6) using logistic and multinomial logistic regression. Analysis was stratified by BMI. Link between BMI and PC risk and aggressive PC was similarly tested. RESULTS: On multivariable analysis, there was no link between exercise and PC diagnosis in the entire cohort (p trend = 0.18-0.71) or across BMI groups (p trend = 0.15-0.97). For the entire cohort, higher BMI was linked with increased risk of high-grade PC (OR 1.06, p = 0.008). When stratified by exercise groups, the trend for higher BMI and increased risk of high-grade PC remained (OR 1.03-1.15, p = 0.02-0.66). There were no interactions between exercise and BMI in predicting PC risk (all p ≥ 0.31). CONCLUSIONS: Regardless of exercise, higher BMI was linked with higher risk of aggressive PC, while exercise was unrelated to PC risk. Confirmatory studies are needed.

Adequacy of Lymph Node Yield for Papillary Thyroid Cancer: An Analysis of 23,131 Patients.

BACKGROUND: Threshold numbers for defining adequacy of lymph node (LN) yield have been determined for evaluation of occult nodal disease during papillary thyroid cancer (PTC) surgery. This study assesses the prevalence of adequate LN yield and estimates its association with patient clinicopathologic characteristics. MATERIALS AND METHODS: Adult patients with cN1 pT1b or pT2 and cN0 or cN1 pT3 M0 PTC ≥1 cm who received surgery with ≥1 LN resected were identified from the National Cancer Database, 2004-2015. Adequate yield was defined as removing ≥6, 9, and 18 LNs for pT1b, pT2, and pT3 stages, respectively, based on recently published literature. Univariable and multivariable logistic regression were used to determine factors associated with adequate yield. RESULTS: A total of 23,131 patients were included; 7544 (32.6%) had adequate LN yield. Rate of adequate yield increased from 19.9% to 36.6% over time. After adjustment, patients at academic facilities were more likely to have adequate yield than those at community centers [OR 1.94 (95% CI 1.55-2.41), P < 0.001]. Patients with more advanced tumors were less likely to have adequate yield (pT1b: 75.9% versus pT2: 64.5% versus pT3: 24.6% adequate LN yield, P < 0.001). Patients with adequate LN yield were 0.89 times likely to receive radioactive iodine compared with those with inadequate yield [OR 0.98 (95% CI 0.81-0.98), P = 0.02]. CONCLUSIONS: The rate of adequate LN yield has increased over time, but only a minority of lymphadenectomies performed for PTC can be defined as adequate. Disparities still exist based on patient and facility characteristics; patients with more advanced tumors appear less likely to have adequate LN yield.

A DIRECT COMPARISON OF THE ATA AND TI-RADS ULTRASOUND SCORING SYSTEMS.

Objective: This study compares the American Thyroid Association (ATA) classification system with the 2017 American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) for predicting cancer risk in thyroid nodules. Methods: This is a retrospective review of ultrasound imaging of all adult patients with thyroid nodules >5 mm who underwent thyroidectomy at a tertiary care hospital in 2016. We assessed the ability of either system to predict malignancy based on surgical histopathology. Sensitivity, specificity, negative predictive values (NPV) and positive predictive values (PPV), and area-under-the-curve (AUC) were calculated and compared using McNemar's, Fisher exact, or DeLong's tests. Results: Three hundred and twenty-three nodules from 213 adults were included. Median patient age was 55 years; 75.6% were female. 27.2% nodules were malignant. Both ATA and ACR TI-RADS provide effective diagnostic performance, a sensitivity of 77.3% versus 78.4%, respectively, a specificity of 76.6% versus 73.2%, respectively, a PPV of 55.3% versus 52.3%, respectively, and a NPV of 90% for both. The level of agreement between the two classification systems was almost perfect (weighted Kappa statistic = 0.93, AUC 0.77 ATA versus 0.76 TI-RADS [P = .18]). However, of the 40 (TI-RADS level 3) TR3 nodules (<2.5 cm), 10% were malignant, and of the 31 (TI-RADS level 4) TR4 nodules (<1.5 cm), 38% were malignant. Conclusion: The ATA and TI-RADS classification systems appear to have similar diagnostic value for predicting thyroid cancer. However, subanalysis of TR3 and TR4 nodules with consideration of size criteria showed that there is a higher risk of missing a malignancy if the ACR TI-RADS recommendation is followed. These results should be validated in a different patient cohort with a lower incidence of cancer. Abbreviations: ACR = American College of Radiology; ATA = American Thyroid Association; FNA = Fine Needle Aspiration; κ = weighted Kappa statistic; NPV = negative predictive values; PPV = positive predictive values; TI-RADS = Thyroid Imaging Reporting and Data System; TR1 = TI-RADS level 1; TR2 = TI-RADS level 2; TR3 = TI-RADS level 3; TR4 = TI-RADS level 4; TR5 = TI-RADS level 5.

USING THE ATA AND ACR TI-RADS SONOGRAPHIC CLASSIFICATIONS AS ADJUNCTIVE PREDICTORS OF MALIGNANCY FOR INDETERMINATE THYROID NODULES.

Objective: Thyroid nodules with indeterminate cytology pose management challenges in clinical practice. The aim of this study was to determine the efficacy of ultrasound features in navigating clinical decision making in thyroid nodules with indeterminate cytology. Methods: We retrospectively reviewed ultrasound imaging from 186 adult patients with thyroid nodules and indeterminate cytology who underwent thyroidectomy at a quaternary hospital from 2010-2017. All nodules were classified based on the American Thyroid Association (ATA) and 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). Nodules were included if good quality pre-operative ultrasound imaging and surgical pathology were available. Results: A total of 202 thyroid nodules were included. The median age was 57 years; 82.8% were female. Risk of malignancy (ROM) in resected nodules with Bethesda 3 and 4 cytology was 19.4% and 30.3%, respectively. ATA high-suspicious and TI-RADS 5 nodules had high ROM, 100% in both systems for Bethesda 3 nodules; 66.7% and 50.0%, respectively, for Bethesda 4 nodules. For ATA very-low suspicious/TI-RADS 1 and 2, ROM was 0%. ROM in ATA low-suspicious/TI-RADS 3 nodules with Bethesda 3 cytology was lower (15.2% and 16.0%, respectively) than Bethesda 4 cytology (33.8% and 34.3%, respectively). ATA intermediate-suspicious/TI-RADS 4 nodules with Bethesda 4 cytology had a lower ROM (11.1% and 18.2%, respectively) than Bethesda 3 cytology (28.6 % and 31.6%, respectively). Conclusion: Using either the ATA or the TI-RADS system to risk-stratify nodules with indeterminate cytology may help clinicians plan better for additional diagnostic testing and treatment. Abbreviations: ACR = American College of Radiology; ATA = American Thyroid Association; AUS = atypia of undetermined significance; FLUS = follicular lesion of undetermined significance; FN = follicular neoplasm; PPV = positive predictive value; ROM = risk of malignancy; SFN = suspicious for follicular neoplasm; TI-RADS = Thyroid Imaging Reporting and Data System.