Publications by authors named "Ryan R Cook"

18 Publications

  • Page 1 of 1

Predictors of having naloxone in urban and rural Oregon findings from NHBS and the OR-HOPE study.

Drug Alcohol Depend 2021 Oct 21;227:108912. Epub 2021 Jul 21.

Public Health Division, Oregon Health Authority, 800 NE Oregon Street, Portland, OR, 97232, USA; Department of Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA. Electronic address:

Purpose: Naloxone is an opioid antagonist that can be effectively administered by bystanders to prevent overdose. We determined the proportion of people who had naloxone and identified predictors of naloxone ownership among two samples of people who inject drugs (PWID) who use opioids in Portland and rural Western Oregon.

Basic Procedures: We used data from participants in Portland's National HIV Behavioral Surveillance (NHBS, N = 477) and the Oregon HIV/Hepatitis and Opioid Prevention and Engagement Study (OR-HOPE, N = 133). For each sample, we determined the proportion of participants who had naloxone and estimated unadjusted and adjusted relative risk of having naloxone associated with participant characteristics.

Main Findings: Sixty one percent of NHBS and 30 % of OR-HOPE participants had naloxone. In adjusted analysis, having naloxone was associated with female gender, injecting goofballs (compared to heroin alone), housing stability, and overdose training in the urban NHBS sample, and having naloxone was associated with drug of choice, frequency of injection, and race in the rural OR-HOPE sample. In both samples, having naloxone was crudely associated with SSP use, but this was attenuated after adjustment.

Principal Conclusions: Naloxone ownership was insufficient and highly variable among two samples of PWID who use opioids in Oregon. People who use methamphetamine, males, and people experiencing homelessness may be at increased risk for not having naloxone and SSP may play a key role in improving access.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.108912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464511PMC
October 2021

HIV clinic-based buprenorphine plus naloxone versus referral for methadone maintenance therapy for treatment of opioid use disorder in HIV clinics in Vietnam (BRAVO): an open-label, randomised, non-inferiority trial.

Lancet HIV 2021 02;8(2):e67-e76

Hanoi Medical University, Hanoi, Vietnam.

Background: UNAIDS recommends integrating methadone or buprenorphine treatment of opioid use disorder with HIV care to improve HIV outcomes, but buprenorphine adoption remains limited in many countries. We aimed to assess whether HIV clinic-based buprenorphine plus naloxone treatment for opioid use disorder was non-inferior to referral for methadone maintenance therapy in achieving HIV viral suppression in Vietnam.

Methods: In an open-label, non-inferiority trial (BRAVO), we randomly assigned people with HIV and opioid use disorder (1:1) by computer-generated random number sequence, in blocks of ten and stratified by site, to receive HIV clinic-based buprenorphine plus naloxone treatment or referral for methadone maintenance therapy in six HIV clinics in Vietnam. The primary outcome was HIV viral suppression at 12 months (HIV-1 RNA ≤200 copies per mL on PCR) by intention to treat (absolute risk difference [RD] margin ≤13%), compared by use of generalised estimating equations. Research staff actively queried treatment-emergent adverse events during quarterly study visits and passively collected adverse events reported during HIV clinic visits. This study is registered with ClinicalTrials.gov, NCT01936857, and is completed.

Findings: Between July 27, 2015, and Feb 12, 2018, we enrolled 281 patients. At baseline, 272 (97%) participants were male, mean age was 38·3 years (SD 6·1), and mean CD4 count was 405 cells per μL (SD 224). Viral suppression improved between baseline and 12 months for both HIV clinic-based buprenorphine plus naloxone (from 97 [69%] of 140 patients to 74 [81%] of 91 patients) and referral for methadone maintenance therapy (from 92 [66%] of 140 to 99 [93%] of 107). Buprenorphine plus naloxone did not demonstrate non-inferiority to methadone maintenance therapy in achieving viral suppression at 12 months (RD -0·11, 95% CI -0·20 to -0·02). Retention on medication at 12 months was lower for buprenorphine plus naloxone than for methadone maintenance therapy (40% vs 65%; RD -0·53, 95% CI -0·75 to -0·31). Participants assigned to buprenorphine plus naloxone more frequently experienced serious adverse events (ten [7%] of 141 vs four of 140 [3%] assigned to methadone maintenance therapy) and deaths (seven of 141 [5%] vs three of 141 [2%]). Serious adverse events and deaths typically occurred in people no longer taking ART or opioid use disorder medications.

Interpretation: Although integrated buprenorphine and HIV care may potentially increase access to treatment for opioid use disorder, scale-up in middle-income countries might require enhanced support for buprenorphine adherence to improve HIV viral suppression. The strength of our study as a multisite randomised trial was offset by low retention of patients on buprenorphine.

Funding: National Institute on Drug Abuse (US National Institutes of Health).
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http://dx.doi.org/10.1016/S2352-3018(20)30302-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082651PMC
February 2021

Prostate-specific antigen kinetics and biochemical control following stereotactic body radiation therapy, high dose rate brachytherapy, and low dose rate brachytherapy: A multi-institutional analysis of 3502 patients.

Radiother Oncol 2020 10 11;151:26-32. Epub 2020 Jul 11.

Department of Radiation Oncology, University of California Los Angeles, Los Angeles, United States.

Background And Purpose: Stereotactic body radiation therapy (SBRT), low dose rate brachytherapy (LDR-BT) and high dose rate brachytherapy (HDR-BT) are ablative-intent radiotherapy options for prostate cancer (PCa). These vary considerably in dose delivery, which may impact post-treatment prostate-specific antigen (PSA) patterns and biochemical control. We compared PSA kinetics between SBRT, HDR-BT, and LDR-BT, and assessed their relationships to biochemical recurrence-free survival (BCRFS).

Methods And Materials: Retrospective PSA data were analyzed for 3502 men with low-risk (n = 2223; 63.5%), favorable intermediate-risk (n = 869; 24.8%), and unfavorable intermediate-risk (n = 410; 11.7%) PCa treated with SBRT (n = 1716; 49.0%), HDR-BT (n = 512; 14.6%), or LDR-BT (n = 1274; 36.4%) without upfront androgen deprivation therapy at 10 institutions from 1990 to 2017. We compared nadir PSA (nPSA), time to nPSA, achievement of nPSA <0.2 ng/mL and <0.5 ng/mL, rates of nPSA <0.4 ng/mL at 4 years, and BCRFS.

Results: Median follow-up was 72 months. Median nPSA and nPSA <0.2 ng/mL were stratified by risk group (interaction p ≤ 0.001). Median nPSA and time to nPSA were 0.2 ng/mL at 44 months after SBRT, 0.1-0.2 ng/mL at 37 months after HDR-BT, and 0.01-0.2 ng/mL at 51 months after LDR-BT (mean log nPSA p ≤ 0.009 for LDR-BT vs. SBRT or HDR-BT for low/favorable intermediate-risk). There were no differences in nPSA <0.4 ng/mL at 4 years (p ≥ 0.51). BCRFS was similar for all three modalities (p ≥ 0.27). Continued PSA decay beyond 4 years was predictive of durable biochemical control.

Conclusion: LDR-BT led to lower nPSAs with longer continued decay compared to SBRT and HDR-BT, but no differences in BCRFS.
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http://dx.doi.org/10.1016/j.radonc.2020.07.014DOI Listing
October 2020

Psychometric properties of measures of substance use: a systematic review and meta-analysis of reliability, validity and diagnostic test accuracy.

BMC Med Res Methodol 2020 05 7;20(1):106. Epub 2020 May 7.

Department of Family Medicine and Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.

Background: Synthesis of psychometric properties of substance use measures to identify patterns of use and substance use disorders remains limited. To address this gap, we sought to systematically evaluate the psychometric properties of measures to detect substance use and misuse.

Methods: We conducted a systematic review and meta-analysis of literature on measures of substance classes associated with HIV risk (heroin, methamphetamine, cocaine, ecstasy, alcohol) that were published in English before June 2016 that reported at least one of the following psychometric outcomes of interest: internal consistency (alpha), test-retest/inter-rater reliability (kappa), sensitivity, specificity, positive predictive value, and negative predictive value. We used meta-analytic techniques to generate pooled summary estimates for these outcomes using random effects and hierarchical logistic regression models.

Results: Findings across 387 paper revealed that overall, 65% of pooled estimates for alpha were in the range of fair-to-excellent; 44% of estimates for kappa were in the range of fair-to-excellent. In addition, 69, 97, 37 and 96% of pooled estimates for sensitivity, specificity, positive predictive value, and negative predictive value, respectively, were in the range of moderate-to-excellent.

Conclusion: We conclude that many substance use measures had pooled summary estimates that were at the fair/moderate-to-excellent range across different psychometric outcomes. Most scales were conducted in English, within the United States, highlighting the need to test and validate these measures in more diverse settings. Additionally, the majority of studies had high risk of bias, indicating a need for more studies with higher methodological quality.
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http://dx.doi.org/10.1186/s12874-020-00963-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203822PMC
May 2020

Rectal Microbiome Alterations Associated With Oral Human Immunodeficiency Virus Pre-Exposure Prophylaxis.

Open Forum Infect Dis 2019 Nov 29;6(11):ofz463. Epub 2019 Oct 29.

Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

Background: Oral daily tenofovir (TFV) disoproxil fumarate/emtricitabine (TDF/FTC) for human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is highly effective for HIVprevention, yet long-term effects are not fully understood. We investigated the effects of PrEP on the rectal microbiome in a cohort of men who have sex with men (MSM).

Methods: This cross-sectional analysis included HIV-negative MSM either on PrEP (n = 37) or not (n = 37) selected from an ongoing cohort using propensity score matching. Rectal swabs were used to examine microbiome composition using 16S ribosomal ribonucleic acid gene sequencing, and associations between PrEP use and microbiota abundance were examined. Hair specimens were used to quantify TFV and FTC exposure over the past 6 weeks on a subset of participants (n = 15).

Results: Pre-exposure prophylaxis use was associated with a significant increase in abundance (adjusted = .015). Similar associations were identified using least absolute shrinkage and selection operator (LASSO) regression, confirming the increase in and also showing increased , , and decreased . Increased was significantly associated with increasing TFV exposure.

Conclusions: Oral TDF/FTC for PrEP is associated with rectal microbiome changes compared to well matched controls, specifically increased and abundance. This study highlights the need for future investigations of the role of microbiome changes on HIV susceptibility and effectiveness of PrEP.
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http://dx.doi.org/10.1093/ofid/ofz463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105055PMC
November 2019

Alterations to the Gastrointestinal Microbiome Associated with Methamphetamine Use among Young Men who have Sex with Men.

Sci Rep 2019 10 16;9(1):14840. Epub 2019 Oct 16.

Department of Epidemiology, Fielding School of Public Health at the University of California, Los Angeles, USA.

Methamphetamine (MA) use is a major public health problem in the United States, especially among people living with HIV (PLWH). Many MA-induced neurotoxic effects are mediated by inflammation and gut microbiota may play a role in this process, yet the effects of MA on the microbiome have not been adequately explored. Therefore, we performed 16S rRNA gene sequencing on rectal swab samples from 381 men who have sex with men, 48% of whom were PLWH and 41% of whom used MA. We compared microbiome composition between MA users and non-users while testing for potential interactions with HIV and controlling for numerous confounders using inverse probability of treatment weighting. We found that MA use explained significant variation in overall composition (R = 0.005, p = 0.008) and was associated with elevated Finegoldia, Parvimonas, Peptoniphilus, and Porphyromonas and reduced Butyricicoccus and Faecalibacterium, among others. Genera including Actinomyces and Streptobacillus interacted with HIV status, such that they were increased in HIV+ MA users. Finegoldia and Peptoniphilus increased with increasing frequency of MA use, among others. In summary, MA use was associated with a microbial imbalance favoring pro-inflammatory bacteria, including some with neuroactive potential and others that have previously been associated with poor HIV outcomes.
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http://dx.doi.org/10.1038/s41598-019-51142-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795845PMC
October 2019

Prostate-only Versus Whole-pelvis Radiation with or Without a Brachytherapy Boost for Gleason Grade Group 5 Prostate Cancer: A Retrospective Analysis.

Eur Urol 2020 01 13;77(1):3-10. Epub 2019 Apr 13.

Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.

Background: The role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases.

Objective: To assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT).

Design, Setting, And Participants: We identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT).

Outcome Measurements And Statistical Analysis: Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment.

Results And Limitations: A total of 299 EBRT patients (41%) and 320 EBRT+BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2-0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6-1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7-1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4-1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3-1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2-1.2, p=0.1 for PCSS).

Conclusions: WPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted.

Patient Summary: When men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.
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http://dx.doi.org/10.1016/j.eururo.2019.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521828PMC
January 2020

Effects of HIV viremia on the gastrointestinal microbiome of young MSM.

AIDS 2019 04;33(5):793-804

Department of Epidemiology, Fielding School of Public Health at the University of California.

Objective: We employed a high-dimensional covariate adjustment method in microbiome analysis to better control for behavioural and clinical confounders, and in doing so examine the effects of HIV on the rectal microbiome.

Design: Three hundred and eighty-three MSM were grouped into four HIV viremia categories: HIV negative (n = 200), HIV-positive undetectable (HIV RNA < 20 copies/ml; n = 66), HIV-positive suppressed (RNA 20-200 copies/ml; n = 72) and HIV-positive viremic (RNA > 200 copies/ml; n = 45).

Methods: We performed 16S rRNA gene sequencing on rectal swab samples and used inverse probability of treatment-weighted marginal structural models to examine differences in microbial composition by HIV viremia category.

Results: HIV viremia explained a significant amount of variability in microbial composition in both unadjusted and covariate-adjusted analyses (R = 0.011, P = 0.02). Alterations in bacterial taxa were more apparent with increasing viremia. Relative to the HIV-negative group, HIV-positive undetectable participants showed depletions in Brachyspira, Campylobacter and Parasutterella, while suppressed participants demonstrated depletions in Barnesiella, Brachyspira and Helicobacter. The microbial signature of viremic men was most distinct, showing enrichment in inflammatory genera Peptoniphilus, Porphyromonas and Prevotella and depletion of Bacteroides, Brachyspira and Faecalibacterium, among others.

Conclusion: Our study shows that, after accounting for the influence of multiple confounding factors, HIV is associated with dysbiosis in the gastrointestinal microbiome in a dose-dependent manner. This analytic approach may allow for better identification of true microbial associations by limiting the effects of confounding, and thus improve comparability across future studies.
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http://dx.doi.org/10.1097/QAD.0000000000002132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422698PMC
April 2019

Content Validity of Anatomic Site-Specific Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Item Sets for Assessment of Acute Symptomatic Toxicities in Radiation Oncology.

Int J Radiat Oncol Biol Phys 2018 09 5;102(1):44-52. Epub 2018 Jun 5.

Department of Radiation Oncology, University of California, Los Angeles, California. Electronic address:

Purpose: To improve assessment of symptomatic toxicity in cancer clinical trials and complement clinician-based toxicity reporting, the US National Cancer Institute developed a measurement system called the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). The objective of this study was to examine the content validity of PRO-CTCAE in patients undergoing radiation therapy and to establish anatomic site-specific item sets for implementation in cancer research.

Methods And Materials: Patients receiving radiation to the brain, head and neck, breast, thorax, abdomen, or pelvis were recruited during the final week of radiation. Participants described side effects qualitatively and completed anatomic site-specific checklists indicating the presence or absence of symptomatic toxicities drawn from the PRO-CTCAE library. Items endorsed by ≥20% of participants were selected for inclusion. Symptomatic toxicities described qualitatively were content analyzed and summarized. Symptomatic toxicities not reflected in the PRO-CTCAE item library were tabulated.

Results: We conducted 389 interviews of patients receiving radiation to the brain (n = 46), head and neck (n = 69), breast (n = 134), thorax (n = 30), abdomen (n = 27), female pelvis (n = 36), or male pelvis (n = 47). Median age was 62 years; 62% were female. The 53 solicited PRO-CTCAE symptoms reflected all reported radiation-induced toxicities with the exception of phlegm/mucus production and mouth/throat pain with swallowing in patients receiving head and neck radiation, eye dryness/irritation in patients undergoing brain radiation, and obstructive urinary symptoms in men receiving pelvic radiation. The PRO-CTCAE items "skin burns" and "pain" require greater specificity to adequately reflect toxicities experienced during radiation.

Conclusions: PRO-CTCAE demonstrates strong content validity as a measure of symptomatic toxicities in patients receiving radiation. These results provide empirical support for the definition of site-specific PRO-CTCAE item sets to assess the symptomatic toxicities of radiation therapy. The site-specific PRO-CTCAE item sets developed herein are currently being deployed in our department via an electronic platform to capture treatment-related toxicity.
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http://dx.doi.org/10.1016/j.ijrobp.2018.04.048DOI Listing
September 2018

Optimal Treatment for High-Risk Prostate Cancer-Reply.

JAMA 2018 07;320(4):405

Department of Radiation Oncology, University of California, Los Angeles.

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http://dx.doi.org/10.1001/jama.2018.6721DOI Listing
July 2018

Clinical Outcomes for Patients With Gleason Score 10 Prostate Adenocarcinoma: Results From a Multi-institutional Consortium Study.

Int J Radiat Oncol Biol Phys 2018 07 5;101(4):883-888. Epub 2018 Apr 5.

Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, California.

Purpose: Gleason score (GS) 10 disease is the most aggressive form of clinically localized prostate adenocarcinoma (PCa). The long-term clinical outcomes and overall prognosis of patients presenting with GS 10 PCa are largely unknown because of its rarity.

Methods And Materials: The study included 112 patients with biopsy-determined GS 10 PCa who received treatment with radical prostatectomy (RP, n = 26), external beam radiation therapy (EBRT, n = 48), or EBRT with a brachytherapy boost (EBRT-BT, n = 38) between 2000 and 2013. Propensity scores were included as covariates for comparative analysis. Overall survival, prostate cancer-specific survival, and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method with inverse probability of treatment weighting to control for confounding.

Results: The median follow-up period was 4.9 years overall (3.9 years for RP, 4.8 years for EBRT, and 5.7 years for EBRT-BT). Significantly more EBRT patients than EBRT-BT patients received upfront androgen deprivation therapy (98% vs 79%, P < .01 by χ test), though the durations were similar (median, 24 months vs 22.5 months). Of the RP patients, 34% received postoperative EBRT, and 35% received neoadjuvant systemic therapy. The propensity score-adjusted 5-year overall survival rate was 80% for the RP group, 73% for the EBRT group, and 83% for the EBRT-BT group. The corresponding adjusted 5-year prostate cancer-specific survival rates were 87%, 75%, and 94%, respectively. The EBRT-BT group trended toward superior DMFS when compared with the RP group (hazard ratio, 0.3; 95% confidence interval 0.1-1.06; P = .06) and had superior DMFS when compared with the EBRT group (hazard ratio, 0.4; 95% confidence interval 0.1-0.99; P = .048).

Conclusions: To our knowledge, this is the largest series ever reported on the clinical outcomes of patients with biopsy-determined GS 10 PCa. These data provide useful prognostic benchmark information for physicians and patients. Aggressive therapy with curative intent is warranted, as >50% of patients remain free of systemic disease 5 years after treatment.
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http://dx.doi.org/10.1016/j.ijrobp.2018.03.060DOI Listing
July 2018

A Prospective Phase 2 Study Evaluating Safety and Efficacy of Combining Stereotactic Body Radiation Therapy With Heat-based Ablation for Centrally Located Lung Tumors.

Int J Radiat Oncol Biol Phys 2018 07 21;101(3):564-573. Epub 2018 Mar 21.

Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California. Electronic address:

Purpose: Stereotactic body radiation therapy (SBRT) and heat-based ablation (HBA) are both potentially safe and effective treatments for primary and metastatic lung tumors. Both are suboptimal for centrally located tumors, with SBRT having a higher risk of significant toxicity and HBA having lower efficacy. This study evaluates the safety and efficacy of combination SBRT-HBA to determine whether combined treatment can result in superior outcomes to each treatment alone.

Methods And Materials: Patients with 1 or 2 primary or metastatic lung tumors ≤ 5 cm in size were enrolled in a prospective phase 2 trial and treated with SBRT in 3 fractions followed by HBA. Tumors < 1 cm from the central bronchial tree received a total of 36 Gy, and tumors 1 to 2 cm away received 42 Gy. HBA was delivered within 10 days after SBRT. The primary endpoints were local control, toxicity, and degree of decline in lung function. The secondary endpoints were progression-free survival and overall survival.

Results: We treated 16 patients with 17 tumors. The median follow-up time was 26 months. Fifteen tumors were evaluable for local control. The 1- and 2-year actuarial local control rates were 93% and 81%, respectively. Three patients had grade ≥ 3 toxicity: bronchial stenosis, pain, and pulmonary hemorrhage. The percent predicted forced expiratory volume in 1 second and functional vital capacity decreased by 8% and 8.5%, respectively, at 3 months after treatment (P < .001 for both).

Conclusions: Combining SBRT and HBA for centrally located lung tumors offers reasonable local control and toxicity despite the anatomic challenges of this location. HBA may be a reasonable supplement to SBRT when trachea and bronchus, large vessel, or esophageal constraints cannot be met with full-dose SBRT and a biologically effective dose < 100 Gy is delivered because of an ultra-central location or large tumor size.
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http://dx.doi.org/10.1016/j.ijrobp.2018.03.011DOI Listing
July 2018

Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer.

JAMA 2018 03;319(9):896-905

Department of Urology, University of California, Los Angeles.

Importance: The optimal treatment for Gleason score 9-10 prostate cancer is unknown.

Objective: To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment.

Design, Setting, And Participants: Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013.

Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy.

Main Outcomes And Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis-free survival and overall survival were secondary outcomes.

Results: Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer-specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer-specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer-specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]).

Conclusions And Relevance: Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer-specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.
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http://dx.doi.org/10.1001/jama.2018.0587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885899PMC
March 2018

Psychosocial correlates of patient-provider family planning discussions among HIV-infected pregnant women in South Africa.

Open Access J Contracept 2017 3;8:25-33. Epub 2017 Apr 3.

Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.

Patient-provider family planning discussions and preconception counseling can reduce maternal and neonatal risks by increasing adherence to provider recommendations and antiretroviral medication. However, HIV-infected women may not discuss reproductive intentions with providers due to anticipation of negative reactions and stigma. This study aimed to identify correlates of patient-provider family planning discussions among HIV-infected women in rural South Africa, an area with high rates of antenatal HIV and suboptimal rates of prevention of mother-to-child transmission (PMTCT) of HIV. Participants were N=673 pregnant HIV-infected women who completed measures of family planning discussions and knowledge, depression, stigma, intimate partner violence, and male involvement. Participants were, on average, 28 ± 6 years old, and half of them had completed at least 10-11 years of education. Most women were unemployed and had a monthly income of less than ~US$76. Fewer than half of the women reported having family planning discussions with providers. Correlates of patient-provider family planning discussions included younger age, discussions about PMTCT of HIV, male involvement, and decreased stigma ( < 0.05). Depression was indirectly associated with patient-provider family planning discussions through male involvement ( = -0.010, bias-corrected 95% confidence interval [bCI] [-0.019, -0.005]). That is, depression decreased male involvement, and in turn, male involvement increased patient-provider family planning discussions. Therefore, by decreasing male involvement, depression indirectly decreased family planning discussions. Study findings point to the importance of family planning strategies that address depression and facilitate male involvement to enhance communication between patients and providers and optimize maternal and neonatal health outcomes. This study underscores the need for longitudinal assessment of men's impact on family planning discussions both pre- and postpartum. Increasing support for provision of mental health services during pregnancy is merited to ensure the health of pregnant women living with HIV and their infants.
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http://dx.doi.org/10.2147/OAJC.S134124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473338PMC
April 2017

Standard fractionation external beam radiotherapy with and without intraoperative radiotherapy for locally recurrent rectal cancer: the role of local therapy in patients with a high competing risk of death from distant disease.

Br J Radiol 2017 Aug 14;90(1076):20170134. Epub 2017 Jun 14.

2 Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.

Objective: We sought to evaluate the effectiveness and safety of utilizing radiotherapy (RT) with standard fractionation, with or without intraoperative RT (IORT), to treat locally recurrent rectal cancer (LRRC).

Methods: Retrospective review of 25 patients with LRRC treated with standard fractionation RT from 2005 to 2011. 15 patients (60%) had prior pelvic RT and 10 (40%) had synchronous metastases. The median equivalent dose in 2-Gy fractions was 30 and 49.6 Gy in patients with and without prior RT, respectively. 23 patients (92%) received concurrent chemotherapy and 16 (64%) underwent surgical resection. Eight patients (33.3%, four with and four without prior RT) received IORT. A competing risks model was developed to estimate the cumulative incidence of local failure with death treated as a competing event.

Results: Median follow-up was 36.9 months after the date of local recurrence. 3-year rates of overall survival (OS), local control (LC) and death with LC were 51.6%, 73.3% and 69.2%, respectively. On multivariable analysis, surgical resection was significantly predictive of improved OS (p < 0.05). If surgical resection were removed from the multivariable model, given the collinearity between IORT delivery and surgical resection, then IORT also became a significant predictor of OS (p < 0.05). Systemic disease at the time of local recurrence was not associated with either LC or OS. No patient had grade ≥3 acute or late toxicity.

Conclusion: RT with standard fractionation is safe and effective in the treatment of patients with LRRC, even in patients with significant risk of systemic disease and/or history of prior RT. Advances in knowledge: The utility of RT with standard fractionation, generally with chemotherapy, in the treatment of LRRC is demonstrated. In this high-risk cohort of patients with a 40% incidence of synchronous metastatic disease, surgical resection of the recurrence was the major predictor of OS, though a benefit to IORT was also suggested. No patients had grade ≥3 acute or late toxicity, though 40% had undergone prior RT, underscoring the tolerability of standard fractionation RT in this setting.
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http://dx.doi.org/10.1259/bjr.20170134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603953PMC
August 2017

Treatment trends for patients with brain metastases: Does practice reflect the data?

Cancer 2017 Jun 8;123(12):2274-2282. Epub 2017 Feb 8.

Department of Radiation Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.

Background: Published guidelines regarding the optimal treatment strategies for brain metastases focus on patients with ≤3 lesions. As delivery techniques for stereotactic radiosurgery (SRS) improve, radiation oncologists are increasingly using it for patients with >3 metastases. In the current study, the authors sought to characterize practice patterns among practitioners to identify areas of controversy.

Methods: A survey of practicing radiation oncologists was distributed via e-mail. Responses were collected from April 1 to May 5, 2016. Survey data were analyzed.

Results: A total of 711 currently practicing radiation oncologists responded, for a response rate of 12.5%. Specialists in central nervous system tumors (CNS specialists) were more likely to treat higher numbers of patients with brain metastases with SRS. There was a significant difference in the optimal "cutoff number" used when deciding how many lesions to treat with SRS versus whole-brain radiotherapy. Cutoff numbers were significantly higher for high-volume CNS specialists (≥10 patients/month) than for either low-volume CNS specialists (5-9 patients/month) or high-volume, non-CNS specialists (8.1 vs 5.6 and 5.1, respectively; P<.001). A majority of respondents (56%) identified patients with 4 to 6 brain metastases as being the most challenging patients to treat.

Conclusions: To the authors' knowledge, there appears to be no consensus regarding the optimal treatment strategy among patients with >3 brain metastases, and practice patterns are heterogeneous. Radiation oncologists, especially high-volume CNS specialists, are treating significantly more brain metastases with SRS than what currently is recommended by published consensus guidelines. Providers struggle with patients with a moderate intracranial disease burden. Further prospective studies are needed to support these practice patterns and guide decision making. Cancer 2017;123:2274-2282. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30607DOI Listing
June 2017

Treatment trends for patients with brain metastases: Does practice reflect the data?

Cancer 2017 Jun 8;123(12):2274-2282. Epub 2017 Feb 8.

Department of Radiation Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.

Background: Published guidelines regarding the optimal treatment strategies for brain metastases focus on patients with ≤3 lesions. As delivery techniques for stereotactic radiosurgery (SRS) improve, radiation oncologists are increasingly using it for patients with >3 metastases. In the current study, the authors sought to characterize practice patterns among practitioners to identify areas of controversy.

Methods: A survey of practicing radiation oncologists was distributed via e-mail. Responses were collected from April 1 to May 5, 2016. Survey data were analyzed.

Results: A total of 711 currently practicing radiation oncologists responded, for a response rate of 12.5%. Specialists in central nervous system tumors (CNS specialists) were more likely to treat higher numbers of patients with brain metastases with SRS. There was a significant difference in the optimal "cutoff number" used when deciding how many lesions to treat with SRS versus whole-brain radiotherapy. Cutoff numbers were significantly higher for high-volume CNS specialists (≥10 patients/month) than for either low-volume CNS specialists (5-9 patients/month) or high-volume, non-CNS specialists (8.1 vs 5.6 and 5.1, respectively; P<.001). A majority of respondents (56%) identified patients with 4 to 6 brain metastases as being the most challenging patients to treat.

Conclusions: To the authors' knowledge, there appears to be no consensus regarding the optimal treatment strategy among patients with >3 brain metastases, and practice patterns are heterogeneous. Radiation oncologists, especially high-volume CNS specialists, are treating significantly more brain metastases with SRS than what currently is recommended by published consensus guidelines. Providers struggle with patients with a moderate intracranial disease burden. Further prospective studies are needed to support these practice patterns and guide decision making. Cancer 2017;123:2274-2282. © 2017 American Cancer Society.
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June 2017
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