Brentuximab vedotin with AVD for stage II-IV HIV-related Hodgkin lymphoma (AMC 085): phase 2 results from an open-label, single arm, multicentre phase 1/2 trial.

BACKGROUND: Brentuximab vedotin in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is approved in the upfront setting for advanced stage classical Hodgkin lymphoma (cHL). People living with HIV have been excluded from these studies. We aimed to understand the activity and safety of brentuximab vedotin-AVD in people living with HIV diagnosed with Hodgkin lymphoma, while focusing on HIV disease parameters and antiretroviral therapy (ART) interactions. METHODS: We present the phase 2 portion of a multicentre phase 1/2 study. Eligible patients were 18 years or older, had untreated stage II-IV HIV-associated cHL (HIV-cHL), a Karnofsky performance status of more than 30%, a CD4+ T-cell count of 50 cells per µL or more, were required to take ART, and were not on strong CYP3A4 or P-glycoprotein inhibitors. Patients were treated intravenously with 1·2 mg/kg of brentuximab vedotin (recommended phase 2 dose) with standard doses of AVD for six cycles on days 1 and 15 of a 28-day cycle. The primary endpoint of the phase 2 portion was 2-year progression-free survival (PFS), assessed in all eligible participants who began treatment. Accrual has been completed. This trial is registered at ClinicalTrials.gov, NCT01771107. FINDINGS: Between March 8, 2013, and March 7, 2019, 41 patients received study therapy with a median follow up of 29 months (IQR 16-38). 34 (83%) of 41 patients presented with stage III-IV and seven (17%) with stage II unfavourable HIV-cHL. 37 (90%) of 41 patients completed therapy, all 37 of whom achieved complete response. The 2-year PFS was 87% (95% CI 71-94) and the overall survival was 92% (78-97). The most common grade 3 or worse adverse events were peripheral sensory neuropathy (four [10%] of 41 patients), neutropenia (18 [44%]), and febrile neutropenia (five [12%]). One treatment-related death was reported, due to infection. INTERPRETATION: Brentuximab vedotin-AVD was highly active and had a tolerable adverse event rate in HIV-cHL and is an important therapeutic option for people with HIV-cHL. The complete reponse rate is encouraging and is possibly related to a unique aspect of HIV-cHL biology. Upcoming 5-year data will evaluate the sustainability of the outcomes obtained. FUNDING: National Institutes of Health and National Cancer Institute.

Cleaning the dose falloff with low modulation in SBRT lung plans.

Purpose.This dosimetric study is intended to lower the modulation factor in lung SBRT plans generated in the Eclipse TPS that could replace highly modulated plans that are prone to the interplay effect.Materials and methods.Twenty clinical lung SBRT plans with high modulation factors (≥4) were replanned in Varian Eclipse TPS version 15.5 utilizing 2 mm craniocaudal and 1 mm axial block margins followed by light optimization in order to reduce modulation. A unique plan optimization methodology, which utilizes a novel shell structure (OptiForR50) for R50%optimization in addition to five consecutive concentric 5 mm shells, was utilized to control dose falloff according to RTOG 0813 and 0915 recommendations. The prescription varied from 34-54 Gy in 1-4 fractions, and the dose objectives were PTV D95%= Rx, PTV Dmax< 140% of Rx, and minimizing the modulation factor. Plan evaluation metrics included modulation factor, CIRTOG, homogeneity index (HI), R50%, D2cm, V105%, and lung V8-12.8Gy(Timmerman Constraint). A random-intercept linear mixed effects model was used with a p ≤ 0.05 threshold to test for statistical significance.Results.The retrospectively generated plans had significantly lower modulation factors (3.65 ± 0.35 versus 4.59 ± 0.54; p < 0.001), lower CIRTOG(0.97 ± 0.02 versus 1.02 ± 0.06; p = 0.001), higher HI (1.35 ± 0.06 versus 1.14 ± 0.04; p < 0.001), lower R50%(4.09 ± 0.45 versus 4.56 ± 0.56; p < 0.001), and lower lungs V8-12.8Gy(Timmerman) (4.61% ± 3.18% versus 4.92% ± 3.37%; p < 0.001). The high dose spillage V105%was borderline significantly lower (0.44% ± 0.49% versus 1.10% ± 1.64%; p = 0.051). The D2cmwas not statistically different (46.06% ± 4.01% versus 46.19% ± 2.80%; p = 0.835).Conclusion.Lung SBRT plans with significantly lower modulation factors can be generated that meet the RTOG constraints, using our planning strategy.

The effect of anticonvulsants on survival among patients with GBM brain tumors undergoing radiation: A SEER-Medicare analysis.

BACKGROUND: Patients with glioblastoma multiforme (GBM) who undergo radiation often require anticonvulsants during treatment. The aim of this study was to determine the effects of anticonvulsants on GBM clinical outcomes. METHODS: A retrospective analysis was performed using the SEER-Medicare database. All patients with GBM who were treated with radiation and concurrently taking an anticonvulsant were included in final analysis. Each class of medication was further subdivided by mechanism of action. Descriptive statistics were performed for all variables. Kaplan Meier survival curves were generated for each class of medication and Cox regression analysis was performed to assess the effect of each individual variable on survival. RESULTS: There were 1561 patients available for final analysis. On multivariate Cox regression analysis, GBM patients taking sodium/calcium (Na/Ca) channel blocker anticonvulsants during radiation therapy demonstrated both improved overall survival (OS) (HR, 0.799; 95% CI [0.716, 0.891]; P < 0.001) and cancer specific survival (CSS) (HR, 0.814; 95% CI [0.727, 0.911]; P < 0.001). CONCLUSION: OS was significantly better in patients taking NA/Ca channel blockers among patients with GBM who were concurrently undergoing radiation therapy.

Statewide trends and factors associated with genetic testing for hereditary cancer risk in Arkansas 2013-2018.

BACKGROUND: Early identification of hereditary cancer risk would save lives, but genetic testing (GT) has been inadequate. We assessed i) trends for hereditary breast and ovarian cancer (HBOC), Lynch syndrome, and other GT and ii) factors associated with receipt of GT. METHODS: We used data from the Arkansas All-Payer Claims Database from January 2013 through June 2018 (commercial, Medicaid), December 2017 (state employee), or December 2016 (Medicare) and identified enrollees with ≥1 month of enrollment. Using Current Procedural Terminology (CPT-4) codes, rates for GT were calculated per 100,000 person-quarters and time series regressions estimated. Second, GT and covariate information for enrollees with 24 months of continuous enrollment were used to estimate separate logistic regression models for each GT category. RESULTS: Among 2,520,575 unique enrollees, HBOC testing rates were 2.2 (Medicaid), 22.0 (commercial), 40.4 (state employee), and 13.1(Medicare) per 100,000 person-quarters and increased linearly across all plans. Older age (OR=1.24; 95%CI 1.20 - 1.28), female sex (OR=18.91; 95%CI 13.01 - 28.86), higher comorbidity burden (OR=1.08; 95%CI 1.05 - 1.12), mental disorders (OR=1.53; 95%CI 1.15 - 2.00), and state employee coverage (OR=1.65; 95%CI 1.37 - 1.97) were positively associated with HBOC testing. Less than 1 of 10,000 enrollees received Lynch syndrome testing, while < 5 of 10,000 received HBOC testing. CONCLUSION: GT rates for hereditary cancer syndromes have increased in Arkansas but remain low. Receipt of GT was explained with high discrimination by sex and plan type. IMPACT: Expansion of GT for hereditary cancer risk in Arkansas is needed to identify high-risk individuals who could benefit from risk-reduction strategies.

#Brachytherapy: Physicians As Influencers on Instagram.

Purpose We aimed to evaluate brachytherapy-related posts on Instagram by identifying patient concerns, the content of related posts, and user outreach. Methods and materials A list of top posts from searching #brachytherapy on May 7, 2021, were generated on a mobile device and all data are representative as of May 7, 2021. Searching for #brachytherapy resulted in 1010 posts which were analyzed using Instagram. The content was categorized by source (physician, patient, hospital, or not otherwise specified), type (education or experiences), disease site (cervical, endometrial, other), and user influence (number of posts, number of followers). Patient posts were specifically analyzed and all captions and hashtags were reviewed. Results The distribution of users with brachytherapy-related posts was as follows: 23% patients, 15% physicians, 9% hospitals, 53% not otherwise specified. Physicians only made up 11% of posts analyzed while the majority, 79%, were from patients and other Instagram users. From the accounts linked to patients, 99% of them were experience-based and 1% were educational. Posts made by physicians were educational in content 66% of the time, with 34% of posts being experiences. The median number of followers from least to greatest were not otherwise specified (NOS) 450.5, patients (501), hospital-affiliated (527), and physicians (608). In gynecological cancer patients, the reported side effects were as follows: fatigue 31%, gastrointestinal (GI) 16%, genitourinary (GU) 16%, pain 28%, and anxiety 50%. Conclusion: This study shows the influential power physicians have on social media and the need for increased brachytherapy awareness on platforms such as Instagram. Patients have voiced apprehension to pursue radiation due to lack of information provided and fear of the unknown. With this concern in mind, physicians are responsible to increase the availability of knowledge to patients in a more relaxed environment than the clinic. With increased physician social media presence, patients will have another avenue for support and reliable source of treatment information.

Safety and Tolerability of Carboplatin and Paclitaxel in Cancer Patients with HIV (AMC-078), an AIDS Malignancy Consortium (AMC) Study.

BACKGROUND: Persons living with human immunodeficiency virus are an underserved population for evidence-based cancer treatment. Paclitaxel and carboplatin (PCb) is an active regimen against a variety of solid tumors, including several seen in excess in patients with HIV infection. We performed a pilot trial to evaluate the safety of full-dose PCb in people living with human immunodeficiency virus and cancer. METHODS: Eligible patients, stratified by concurrent antiretroviral therapy (ART) that included CYP3A4 inhibitors or not, received paclitaxel (175 mg/m2) in combination with carboplatin (target AUC 6) intravenously every 3 weeks for up to 6 cycles. RESULTS: Sixteen evaluable patients received 64 cycles of PCb, including 6 patients treated with CYP3A4 inhibiting ART (ritonavir). The adverse event profile was consistent with the known toxicity profile of PCb, with no differences between the 2 strata. There were 4 partial responses (25%, 95% CI: 7%-52%), and overall, CD4+ lymphocyte count was similar after completion of therapy (median: 310/µL) compared with baseline values (median: 389/µL). Pharmacokinetic studies in 6 patients revealed no significant differences in Cmax or AUCinf for paclitaxel between the 2 cohorts. CONCLUSION: Full doses of PCb chemotherapy are tolerable when given concurrently with ART in people living with human immunodeficiency virus with cancer, including patients receiving CYP3A4 inhibitors. CLINICALTRIALS.GOV IDENTIFIER: NCT01249443.

A dosimetric comparative analysis of Brainlab elements and Eclipse RapidArc for spine SBRT treatment planning.

Purpose. This is a dosimetric study comparing stereotactic body radiotherapy (SBRT) plans of spine tumors using Brainlab Elements Spine planning module against Eclipse RapidArc plans. Dose conformity, dose gradient, dose fall-off, and patient-specific quality assurance (QA) metrics were evaluated. Methods:Twenty patients were immobilized in supine position using half Vac-Lok. A prescription dose of 16 Gy in a single fraction was planned for Varian TrueBeam. Conformal arc plans were generated with Pencil beam (PB), MonteCarlo (MC) in Elements, and RapidArc with Acuros XB algorithm in Eclipse using identical treatment geometry.Results. Eclipse, Elements PB, and Elements MC generated dosimetrically conformal plans having Inverse Paddick Conformity Index (IPCI) <1.3. All plans satisfied the dose constraints to target and OARs. Elements PB had a sharper gradient than Elements MC with average GI of 3.67(95% CI: 3.52-3.82) and 4.06 (95% CI: 3.93-4.20) respectively. Eclipse plans were more homogeneous with mean HI = 1.22 (95% CI: 1.20-1.23) that is lower than others. Average maximum clinical target volume (CTV) doses were higher in Elements MC with 22.31 Gy (95% CI: 21.87-22.74), while PB plans have 21.15 Gy (95% CI: 20.36-21.96), respectively. Elements MC and PB plans had lower average dose to 0.35 c.c. of spinal cord (D0.35cc) of 7.60 Gy (95% CI: 7.18-8.02) and 8.42 Gy (95% CI: 7.83-9.01). All plans had >95% points passing the gamma QA criteria at 3%/2 mm.Conclusion. All treatment plans achieved clinically acceptable target coverage >95% and meet spinal cord dose limits. Smart optimization in Brainlab Elements spine module produced dosimetrically superior plans by better spinal cord sparing.

An Online Survey and Focus Groups for Promoting Cancer Prevention Measures.

In order to design a cancer prevention promotion program in the region, suggestions were solicited at a medical center. We hypothesized that a majority would be native to state, and would be able to articulate about the barriers that may exist. Through online survey and focus groups, suggestions were sought, and the knowledge and the compliance with cancer prevention recommendations were assessed to determine the participants' qualifications as potential educators. Sixty-five point two percent of participants (n = 1018) graduated from high school in Arkansas. The most commonly given suggestions were to provide education to increase awareness, to use social media for promotion, to improve access, and to reduce costs. Self-reported adherence rates to breast, cervical, and colorectal cancer screening were 82.6% (n = 954), 75.8% (n = 541), and 76.7% (n = 453), respectively. Having a personal history of cancer significantly increased colorectal cancer screening uptake (p = 0.04), but paradoxically decreased mammography uptake (p = 0.007). Salary of $40,000 and more and having a Bachelor's degree or higher were associated with higher compliance of Papanicolaou test only (p = 0.007 and p = 0.001, respectively). A majority (67.7%, n = 1056) of respondents expressed willingness to contribute to promoting cancer prevention measures, and 38.3% (n = 559) were willing to participate in focus groups. However, only 6.3% (n = 35) actually participated. The participants' knowledge and compliance appeared to be sufficient, but their follow through in focus group participation was poor.

Assessing the Feasibility of an Online Module for Promoting Cancer Prevention Measures.

OBJECTIVES: The aims of this pilot study were (1) to develop a cancer prevention module consisting of an animated video and a short questionnaire, (2) to assess new knowledge gained by the participants, and (3) to solicit feedback for improving the cancer prevention module. METHODS: Volunteers who previously agreed to be contacted regarding research studies were approached via email. After completing the cancer prevention module, a list of cancer prevention recommendations was provided. Newly gained knowledge was assessed, and feedback was solicited. RESULTS: Overall, 290 of 3165 individuals contacted completed the online module (9.2%), and 38.6% of the participants indicated that they learned something new about cancer prevention measures. A similar proportion, 41.4%, mentioned that they learned about measures that were recommended and due. Paradoxically, response rate was the lowest in the ≥50 year old age group although this group reported the highest rate of learning about new cancer prevention measures. Feedback was favorable in that 70.7% mentioned that the recommendations were helpful to them personally, 69.3% felt motivated to take action to reduce their risk of cancers, and 67% would recommend the online module to their friends and family. CONCLUSION: We developed an online cancer prevention module which seems to be suitable for promoting cancer prevention measures as feedback was favorable, and new knowledge was gained. Future efforts will focus on using the module to promote cancer prevention measures to the general public particularly for the ≥50 year age group.

Predicting risk of progression in relapsed multiple myeloma using traditional risk models, focal lesion assessment with PET-CT and minimal residual disease status.

Not available.

The Use of Crowdfunding to Support Radiation Therapy Cancer Treatments.

BACKGROUND/AIM: The purpose of this study was to assess patients' use of a crowdfunding platform to raise funds for radiation treatment and to better understand the direct and indirect costs associated with treatments. MATERIALS AND METHODS: The GoFundMe crowdfunding database was queried for four unique categories related to radiation treatment campaigns. Covariates identified included clinical and demographic variables, and associations between amount raised and these predictors were analyzed using a generalized linear model. RESULTS: While 56% percent of campaigns cited direct costs associated with treatment, 73.4% of campaigns cited indirect costs related to treatment. Indirect expenses related to travel (31.7%) as well as living expenses (29.2%) were cited most often across all four treatment categories. CONCLUSION: This study enhances understanding regarding patients use of crowdfunding for radiation treatment. Increased focus should be placed on discussing the indirect costs of care with patients and their families.

The Role of Radiotherapy Among Patients With Prostate Ductal Adenocarcinoma.

INTRODUCTION: The aim of this study was to perform a Surveillance, Epidemiology, and End Results (SEER) analysis on the effect of radiotherapy (RT) on survival among patients with prostate ductal adenocarcinoma (DA), a rare variant of prostate cancer. PATIENTS AND METHODS: Cases of T1 to 4 N0 M0 prostate DA diagnosed between 2004 and 2013 were extracted from SEER. The association between categorical variables and radiation therapy was assessed for statistical significance using the χ2 test or Fisher exact test. Difference in continuous variables across the RT groups was assessed for statistical significance using the 2-sample t test or non-parametric test. The distribution of overall survival (OS) and disease-specific survival (DSS) between the RT groups was assessed using the Kaplan-Meier method and the log rank test and after propensity matching. The association between hazards of death (HR) and covariates was examined using Cox proportional hazards model. A 2-sided P-value of .05 was used to determine statistical significance. RESULTS: A total of 205 patients met inclusion criteria. On univariate analysis, RT was associated with significant improvement in OS and DSS. On multivariate Cox regression, RT significantly decreased risk of death for both OS and DSS (HR, 0.516; 95% confidence interval [CI], 0.273-0.978 and HR, 0.232; 95% CI, 0.082-0.658, respectively). After propensity score matching, RT demonstrated a persistent improvement in both OS and DSS. CONCLUSIONS: RT decreased risk of death for both OS and DSS in patients with node-negative, nonmetastatic prostate DA on multivariable analysis. RT was also associated with improved OS and DSS after propensity matching.

Cleaning the dose falloff in lung SBRT plan.

PURPOSE: To investigate a planning technique that can possibly reduce low-to-intermediate dose spillage (measured by R50%, D2cm values) in lung SBRT plans. MATERIALS AND METHODS: Dose falloff outside the target was studied retrospectively in 102 SBRT VMAT plans of lung tumor. Plans having R50% and/or D2cm higher than recommended tolerances in RTOG protocols 0813 and 0915 were replanned with new optimization constraints using novel shell structures and novel constraints. Violations in the RTOG R50% value can be rectified with a dose constraint to a novel shell structure ("OptiForR50"). The construction of structure OptiForR50% and the novel optimization criteria translate the RTOG goals for R50% into direct inputs for the optimizer. Violations in the D2cm can be rectified using constraints on a 0.5 cm thick shell structure with inner surface 2cm from the PTV surface. Wilcoxon signed-rank test was used to compare differences in dose conformity, volume of hot spots, R50%, D2cm of the target in addition to the OAR doses. A two-sided P-value of 0.05 was used to assess statistical significance. RESULTS: Among 102 lung SBRT plans with PTV sizes ranging from 5 to 179 cc, 32 plans with violations in R50% or D2cm were reoptimized. The mean reduction in R50% (4.68 vs 3.89) and D2cm (56.49 vs 52.51) was statistically significant both having P < 0.01. Target conformity index, volume of 105% isodose contour outside PTV, normal lung V20, and mean dose to heart and aorta were significantly lowered with P < 0.05. CONCLUSION: The novel planning methodology using multiple shells including the novel OptiForR50 shell with precisely calculated dimensions and optimizer constraints lead to significantly lower values of R50% and D2cm and lower dose spillage in lung SBRT plans. All plans were successfully brought into the zone of no RTOG violations.

Hemophagocytic lymphohistiocytosis in adults.

Hemophagocytic lymphohistiocytosis (HLH) is an underrecognized disorder due to the variability of its presentation and the fact that in adults, its diagnosis is based on cumbersome, pediatric-based criteria. Data regarding demographics, underlying causes, clinical features, laboratory results, complications, treatments received, and clinical outcomes were collected and analyzed in 41 patients who were diagnosed and treated at University of Arkansas for Medical Sciences between 2007 and 2019. In this group, 51% were male, the median age at diagnosis was 47 years, and 85% (35/41) met the HLH-2004 diagnostic criteria (5/8 variables). When evaluating seven extended variables easily obtained by routine laboratory test, 93% (38/41) of patients met 8 out of 15 criteria. The overall mortality in our patient population was 54% (22/41). The 30-day and 1-year overall survival estimates were 0.73 (95% confidence interval 0.56, 0.84) and 0.46 (95% confidence interval 0.29, 0.62), respectively. Thirty-five patients (85.4%) received HLH-directed therapy, and 19 patients (46.3%) achieved remission. The most common regimen for treating HLH was dexamethasone plus etoposide (53.7%). The patients with malignancy-related HLH had a worse prognosis than those without underlying malignancy, with a 73.33% (11/15) vs 34.62% (9/26) mortality (P = 0.02). In conclusion, despite increasing recognition, HLH remains an enigmatic disorder with increased mortality, even more so with malignancy-associated HLH.

Consumption of Vitamin K and Vitamin A Are Associated With Reduced Risk of Developing Emphysema: NHANES 2007-2016.

Chronic obstructive pulmonary disease (COPD) comprising of emphysema and chronic bronchitis are the most common chronic respiratory diseases that impart a huge economic and clinical burden. Factors other than smoking and air pollutants can cause inflammation and emphysematous changes in the lung airspaces or alveoli have been understudied. Using a cross-sectional study design, we assessed the association of dark green vegetables, vitamin K and Vitamin A with emphysema status among adults at U.S. These nutrients have a role in lung biology. A complete case NHANES data (n = 17,681) was used. After adjusting for modifiable and non-modifiable confounders, consumption of recommended amounts of vitamin K was associated with 39% decrease in odds (Odds Ratio: 0.61; 95% CI: 0.40-0.92, P-val: 0.02) of emphysema. Similarly consumption of recommended amounts vitamin A dose was associated with 33% decrease in odds (Odds Ratio: 0.67; 95% CI: 0.44-1.00, P-val: 0.05) of emphysema. Vitamin K shows an inverse association suggesting that it may be important in slowing the emphysematous process. Vitamin A is important in maintaining the anti-inflammatory process. Together vitamin K and vitamin A are important in the lung health.

Regional trends in average years of potential life lost (AYPLL) secondary to prostate cancer deaths among Caucasians and African Americans treated by surgery or radiation.

PURPOSE: To study regional trends in average years of potential life lost (AYPLL) among Caucasians (CA) and African Americans (AA) with prostate cancer (Pca) who received radical prostatectomy or radiation therapy among four different regions in the US as well as across different tumor grades. Years of potential life lost is defined as the difference between a predetermined end-point age and the age at death for a death that occurred prior to that end age, hence the AYPLL is calculated by dividing the total YPLL by the total number of patients died. METHODS: The surveillance epidemiology and end results (SEER) database was used to identify Pca patients who were CA or AA and who have received radical prostatectomy or radiation therapy. Study duration was divided into four decades; 1973-1982 (D1), 1983-1992 (D2), 1993-2002 (D3), 2003-2012 (D4). Examined regions were; North East (NE), North central (NC), South and West. Tumor grade was classified into; well/moderately differentiated (WD/MD) and poorly/undifferentiated (PD/UD) groups. Differences in AYPLL among CA and AA in each of these variables were compared. RESULTS: Overall, compared to CA, AA were diagnosed and died earlier from Pca. AA had higher AYPLL to Pca than CA. In both tumor grade groups, progressive increase in AYPLL among AA compared to CA was noted over the last three decades. In the WD/MD group, except for the South region, the highest recorded difference in AYPLL between AA and CA was in D4. In the PD/UD group, a similar difference in AYPLL between AA and CA was noted in all regions. The difference in AYPLL was higher in the PD/UD group than the WD/MD group. CONCLUSIONS: Racial disparity between AA and CA existed across the examined regions. It is more pronounced in advanced tumor grades. The differences were more significant in the last decade.

Randomized controlled trial of belladonna and opiate suppository during intravesical onabotulinum toxin A injection.

BACKGROUND: Intravesical injection with onabotulinum toxin A injection can be performed in-office under local anesthesia. Rectally administered pain medication presents a potentially feasible and previously uninvestigated adjunct to office-based anesthesia protocols. OBJECTIVE: The primary aim of this study was to determine whether adding a belladonna and opiate suppository to standard lidocaine instillation resulted in reduction of bladder injection pain during onabotulinum toxin A injection procedure. STUDY DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study of patients undergoing onabotulinum toxin A bladder injection at a single clinic. Patients age ≥18 years, who met clinical criteria for invasive treatment of refractory urinary symptoms, had previously documented postvoid residual volumes <150 mL, and elected for in-office intravesical onabotulinum toxin A injection were eligible to participate. Participants were randomized by computer-generated block randomization to receive a belladonna and opiate (belladonna alkaloid with morphine 16.2/7.5 mg) or placebo suppository. Suppositories were placed immediately prior to lidocaine-based anesthesia, which all participants received. All participants underwent a standardized injection procedure using the same rigid cystoscope, needle type, and injection pattern (20 injections total). A 0-10 numeric rating scale was used to assess pain intensity before anesthesia and suppository, 40 minutes after administration of anesthesia and suppository, after first 10 bladder injections, and immediately after completion of 20 injections. Pain increase during procedure was calculated using the difference between score 40 minutes after administration of anesthesia and suppository and score after first 10 bladder injections. Postvoid residual were measured immediately postprocedure and 2 weeks later. Patient satisfaction with pain control was measured using a Likert scale. Our primary outcome was change in pain level from anesthetic baseline to midprocedure (score after first 10 bladder injections to score 40 minutes after administration of anesthesia and suppository). A final sample size of 26 patients was needed to have 80% power (alpha = 0.05) to detect a 50% reduction in bladder injection pain during the procedure as defined by our primary outcome. An intent-to-treat approach was used for all analyses. RESULTS: In all, 26 participants were enrolled and randomized with 13 in each study arm. Participants in the treatment group were slightly older than in the placebo group (P = .05); there were no statistically significant differences in medical comorbidities. Median score after first 10 bladder injections to score 40 minutes after administration of anesthesia and suppository for the placebo group and treatment group was 4 (range 1-10) and 5 (range 0,9), respectively (P = .94). Median scores immediately after completion of 20 injections for the placebo group and treatment group were 3 (range 0-10) and 2 (range 0,8), respectively (P = .29). There were no significant differences in preinjection pain scores reported before anesthesia and suppository and at 40 minutes after administration of anesthesia and suppository. Postprocedure postvoid residual >200 mL was noted in 5 (38%) of the placebo group and 3 (23%) of the treatment group (P = .67). Two-week postprocedure postvoid residual >200 mL was noted in 3 (25%) of the placebo group and 2 (15%) of the treatment group (P = .64) for an overall rate of 20%. Eleven (84%) participants in each group reported being "mostly satisfied" or "very much satisfied" with pain control. CONCLUSION: Belladonna and opiate suppository use did not significantly reduce bladder injection pain, or increase risk of urinary retention immediately postprocedure or 2 weeks later. Satisfaction with pain control among onabotulinum toxin A injection patients is high.

Very Large Metastases to the Brain: Retrospective Study on Outcomes of Surgical Management.

BACKGROUND: The incidence of brain metastases is rising. To our knowledge, no published study focuses exclusively on brain metastases larger than 4 cm. We present our surgical outcomes for patients with brain metastases larger than 4 cm. METHODS: This is a retrospective chart review of inpatient data at our institution from January 2006 to September 2015. Primary end points included overall survival, progression-free survival, and local recurrence rate. RESULTS: Sixty-one patients had a total of 67 brain metastases larger than 4 cm: 52 were supratentorial and 15 were infratentorial. Forty-three patients underwent surgical resection. Average duration of disease freedom after resection was 4.79 months (range, 0-30 months). Excluding patients with residual on immediate postoperative magnetic resonance imaging, the average rate of local recurrence was 7 months (range, 1-14 months). Overall survival after surgery excluding patients who chose palliation in the immediate postoperative period averaged 8.76 months (range, 1-37 months). Thirty-five of 43 patients (81.4%) had stable or improved neurologic examinations postoperatively. Six patients (13.95%) developed surgical complications. There were 3 major complications (6.98%): 2 pseudomeningoceles required intervention and 1 postoperative hematoma required external ventricular drain placement. There were 3 minor complications (6.98%): 1 self-limited pseudomeningocele, 1 subgaleal fluid collection, and 1 postoperative seizure. CONCLUSIONS: Surgery resulted in stable or improved neurologic examination in 81.4% of cases. On statistical analysis, significantly increased overall survival was noted in patients undergoing surgical resection, and those with higher Karnofsky Performance Scale and lower number of brain metastases at presentation. There is a need for further studies to evaluate management of brain metastases larger than 4 cm.

Prevalence and survival benefit of adjuvant chemotherapy in stage III colon cancer patients: Comparison of overall and age-stratified results by multivariable modeling and propensity score methodology in a population-based cohort.

BACKGROUND: Few population-based studies have assessed the effectiveness of adjuvant chemotherapy (ACT) in stage III colon cancer patients according to age. We sought to quantify the prevalence of ACT use and the absolute and relative survival benefit of ACT overall and by age in a population-based cohort. METHODS: Stage III patients with adenocarcinoma of the colon identified by the Georgia Comprehensive Cancer Registry for the years 2000-07 were eligible (final N=3057). We utilized Poisson regression to obtain adjusted mortality rates (MR) and Cox proportional hazards models to obtain adjusted hazard ratios (HRs) for 5-year overall survival. We evaluated control of confounding by comparing HRs obtained via multivariable modeling (MM), propensity score weighting (PSW), and propensity score matching (PSM). RESULTS: Just over one-third of colon cancer patients did not receive ACT, and the proportion increased with age. Overall, receipt of ACT conferred an absolute (MR difference [No ACT rate-ACT rate] 25.4 deaths/1000 person-years [py], 95% confidence interval [CI]: 19.1-32.7 deaths/1000 py) and relative (MM HR=0.67, 95% CI: 0.59-0.76) survival benefit. The survival benefit was demonstrated across age groups. MM and propensity score methods yielded highly similar HRs. CONCLUSION: Unless contraindicated, efforts to ensure receipt of ACT for stage III colon cancer patients up to 84 years of age are needed to improve the prognosis of patients with node-positive disease.