bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between tobacco use, pain expression, and maladaptive coping among patients with advanced cancer.
Authors: Dev Rony , Kim Yu Jung , Reddy Akhila Sunkepally , Hui David , Tanco Kimberson Cochien , Liu Diane D , Park Minjeong , Williams Janet L. , Carmack Cindy L. , Bruera Eduardo
Published: February 2017

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Background: Cancer patients who smoke have been reported to have higher pain expression and increased risk for opioid abuse. The purpose of our study is to evaluate the association between tobacco use, symptom expression, and maladaptive coping in advanced cancer patients. Methods: We prospectively enrolled advanced cancer patients evaluated in an outpatient Supportive Care Center and collected data on patient demographics, cancer diagnosis, morphine equivalent daily dose (MEDD), cigarette smoking status using Behavioral Risk Factor Surveillance System, symptom expression as measured by Edmonton Symptom Assessment Scale, Cut down/Annoyed/Guilty/Eye opener (CAGE alcoholism questionnaire), short form Screener and Opioid Assessment for Patients with Pain (SOAP-SF) survey, and Brief COPE Questionnaire. Results: Among399 patients, 195 (49%) were never smokers, 158 (40%) former smokers, and 46 (11%) current smokers. The most common malignancies were gastrointestinal (21.1%) and breast (19.5%). Never smokers were more likely to be female (p = 0.005). Current smokers expressed significantly higher pain scores at consultation than former or never smokers [median 7 vs. 6 vs. 5, respectively (p = 0.015)], increased MEDD (median 90 vs. 60 vs. 50, p = 0.002), and more likely to screen CAGE positive (33% vs. 24% vs. 8.7%, p < 0.0001). Compared with former and never smokers, current smokers were significantly more likely to cope with substance use (p = 0.02), denial (p = 0.007), and self-blame (< 0.0001), while both current and former smokers significantly more likely to use venting (p = 0.04). In addition, current smokers compared with former and never smokers were significantly more likely screen positive (≥ 4) on the SOAP-SF survey (74% vs. 13% vs. 9.3%, p = < 0.0001) and clinicians rated patients to be at higher risk for maladaptive coping (6.5% vs 2.5% vs. 1.5%, p = 0.003). Conclusions: In advanced cancer, current and former smokers were significantly more likely to have higher pain expression, CAGE positivity, and increased MEDD at consultation. In addition, a history of current or past tobacco use in advanced cancer patients was associated with increased risk of maladaptive coping.
Assessment tools for palliative care.
Authors: Isenberg Sarina , Aslakson Rebecca , Dy Sydney Morss , Wilson Renee , Waldfogel Julie , Zhang Allen , Blair Alex B. , Robinson Karen
Published: February 2017

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Background: Recent reviews have not comprehensively addressed palliative care (PC) assessment tools. This project summarizes the extent of evidence about PC assessment tools for patients and families, and how tools have been used for clinical care, quality indicators, and evaluation of interventions. Methods: We searched MEDLINE, CINAHL, and Cochrane Database of Systematic Reviews for systematic reviews of assessment tools for PC, from January 2007 to March 2016. We searched the grey literature for domains without systematic reviews, and for domains with systematic reviews > three years old. Paired investigators independently screened search results and grey literature to determine eligibility, and assessed risk of bias of systematic reviews. The team selected the most recent and highest-quality systematic reviews for each domain. One investigator abstracted information, and a second investigator checked the information. Results: Using the National Consensus Project Palliative Care Guidelines domains, we included nine systematic reviews with 167 tools, and six tools from grey literature. Most tools were in physical, psychological, psychiatric, and social aspects of care, care at the end of life, and tools that cross domains (quality of life and caregiver-reported experience). Only two tools directly addressed spiritual aspects and none addressed cultural or patient-reported experience. Internal consistency reliability was evaluated for almost all tools; most reported construct validity; and few reported responsiveness (sensitivity to change). Few studies evaluated the use of assessment tools in quality indicators or clinical practice. A systematic review of 38 PC interventions and the assessment tools used found that at least 25 interventions included physical, psychosocial and psychiatric, and quality of life tools, but the tools varied extensively, and only nine included patient experience tools. Conclusions: Although assessment tools exist in many PC domains, tools are needed to assess spiritual and cultural aspects of care, and patient-reported experience. Research is needed concerning: tools in clinical practice and quality of care; comparison of existing tools; and evaluation and dissemination tools with evidence of responsiveness.
Changing the culture for psychosocial care: Does it need changing?
Authors: Carmack Cindy L. , Parker Patricia A. , Lambert Daphine , Ann-Yi Sujin , Valentine Alan D. , Fossella Frank V. , Bruera Eduardo , Williams Janet L. , Cohen Lorenzo
Published: February 2017

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Background: National organizations recommend routine screening for psychosocial distress in cancer patients. American College of Surgeons (ACoS) Commission on Cancer mandates screening for accreditation with requirements for timing/method/tool for screening; assessment/referral; and documentation. Methods: MD Anderson routinely screens patients for distress with policies and algorithms for the process. We sought to enhance this standard process by incorporating a dedicated psychosocial liaison in the clinic to ensure screening based on NCCN guidelines, follow-up with patients at the medical visit, and clear documentation and referral per ACoS standards. This study compared the standard process to the enhanced process (which occurred in parallel) through a 6-month retrospective chart review of Thoracic Center patients identified as distressed by either process. Results: The enhanced process utilized the Distress Thermometer (DT) cut-off > 4 resulting in optimal specificity (.77) and sensitivity (.64) compared to the standard process using > 6 (specificity = .87; sensitivity = .34). In the enhanced process (N = 71), 99% were seen during the clinic visit, compared to 13% in the standard process (N = 92) (Fishers Exact; P < .0001). In the standard process, 18% were contacted by phone, 10% were seen later while in-patient, and 33% received a phone message; for 26%, no note was dictated. In the enhanced process, there were high rates of documentation of assessments of suicide (100%), depressive symptoms (100%) and anxiety symptoms (96%) compared to the standard process where documentation occurred less often (suicide 5%; depressive symptoms 11%; anxiety symptoms 11%) (Fishers Exact; all P’s < .0001). Conclusions: Results support the institution’s recent practice change to > 4 on the DT. The enhanced process utilizing a psychosocial liaison facilitates screening at the clinic visit and can support existing mental health providers who may have competing responsibilities. Findings also suggest having standards for distress documentation. Overall, the enhanced process fully meets ACoS standards in all required areas.
A comparison of patients with liver cancer receiving palliative care at two Veterans Affairs (VA) Medical Centers.
Authors: Lee Sarah , Wang Zhen , Kothadia Sejal , Wang Yucai , Olson Ellen , Park Yeun-Hee Anna , Klein David , Zhong Fengming , Chang Victor Tsu-Shih
Published: February 2017

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Background: Liver cancer is a leading cause of death. Lack of data exists on palliative care in this group, and care varies by location. We aim to determine if there are differences in palliative care for patients (pts) with liver cancer by VA site. Methods: In an IRB approved protocol, we reviewed medical records of pts at 2 VA medical centers (S1, S2) with liver cancer, who were seen by Palliative Care between 2006 and 2012. Veterans were compared by 1) demographics: Karnofsky performance status > 50 (KPS), marital status, DNR/DNI, 2) palliative intervention: goals of care discussion, referrals to psychology and PT/OT, and 3) outcomes: ED visit within 1 month (mo) of death, ED visit within 6 mo of death, ICU within 30 days of death, and hospice as site of death, time from diagnosis to palliative care, and time from DNR to death. Chi-square, Fisher’s Exact, and T-test were performed with Stata. Results: here were 82 men, 30 from S1 and 52 from S2, median age 61 (35-87) and 63 (54-88) yrs, respectively. Pts were Caucasian 30 (36%), African American 47 (57%), and other 5 (0.1%). Cancer stages were locoregional 15 (50%), metastatic 13 (43%), and unknown 2 (0.1%) at S1 and 28 (54%), 20 (38%), 5 (0.1%) at S2. Differences were seen in KPS > 50: (S1, S2) [10 (33%), 15(29%) p = 0.010], married: (S1, S2) [7 (23%), 24(46%) p = 0.024], DNR/DNI: (S1, S2) [19 (63%), 13(25%), p = 0.001]. Regarding palliative intervention: goals of care discussion (S1, S2) [26 (87%), 44 (85%), p = 0.044], referral to psych (S1, S2) [16 (53%), 42 (81%) p = 0.014], referral to PT/OT (S1, S2) [17 (57%), 15 (29%), p = 0.007]. Finally in regards to outcome: ED visit within 1 mo of death (S1, S2) [7 (23%), 31 (60%), p = 0.001], ED visit within 6 mos of death (S1, S2) [18 (56%), 35 (67%) p = 0.031], ICU within 30 days of death (S1, S2) [0 (0%), 9 (17%) p = 0.019}, and hospice as site of death (S1, S2) [19 (63%), 21 (40%), p < .0001]. Other key differences included median number of days from diagnosis to initial palliative care consult (S1, S2) [97, 39, p = 0.001] and median number of days from DNR to death (S1, S2) [33, 14, p = 0.001]. Conclusions: Results show there are site-specific differences between VA medical centers. These data may be important in the comparison of other centers and provide a baseline for future studies.
Using touch-based technology to screen patients in the ICU.
Authors: Zachariah Finly , Loscalzo Matthew J. , Sidhu Rupinder , Horak David , Buga Sorin
Published: February 2017

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Background: The intensive care unit (ICU) is associated with high mortality rates, significant costs, along with occasionally futile and non-indicated care. Surveys of patients indicate the majority wish to focus on comfort and being at home at the end of life as opposed to the aggressive interventions received in the hospital. Although a small percentage of patients may be awake, medical teams look to the families to provide the direction of care for a patient in the ICU. City of Hope National Medical Center has utilized tablet-based screening of caregivers for years, and now in conjunction with delirium screening has started to roll out tablet-based screening for patients who are awake and do not have delirium. Methods: In parallel with a task force working to assess and address delirium in the hospital, team members from the Department of Supportive Care Medicine and the ICU developed and tested a survey on a tablet-based screening platform. Awake patients are screened for delirium using the confusion assessment method (CAM-ICU). If patients are awake and have a “negative” CAM-ICU, they are provided a tablet to take a five question survey. The questions were written to the sixth grade language level, reviewed by the Patient and Family Advisory Council and non-ICU patients commented on comprehension and emotional response prior to implementation in the ICU. The questions covered topics including orientation, symptoms to be addressed and confidence level in communicating wishes and values. Results: We have successfully administered tablet-based screening for five patients in the ICU, including one on a ventilator with a tracheostomy. Responses are electronically sent to the medical team. By the time of the conference, we will have screened over 50 patients, including patients who are intubated. Conclusions: Assessment of patient wishes and values should be done far before a patient enters the ICU. Unfortunately this does not always occur. This tablet-based screening pilot was a test of concept for feasibility. Although not ideal, capturing a patient’s values and wishes in the ICU has the potential to further assure care plans are individualized, minimize unwanted treatment options and facilitate possible transitions and improved care.
Oncology massage impact on patient with cancer and caregiver self-reported symptoms as part of an integrative oncology program at a comprehensive cancer center.
Authors: Lopez Gabriel , Milbury Kathrin , Spelman Amy , Wei Qi , Sumler Pamela A , Beinhorn Curtiss M , Bruera Eduardo , Cohen Lorenzo
Published: February 2017

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Background: Massage as a manual therapy has shown benefit for symptomatic relief in patients with cancer and their caregivers. We explored the impact of a single massage session on self-reported symptoms in an outpatient clinic at a comprehensive cancer center. Methods: Patients and caregivers received oncology massage treatments (30 or 60-min duration) at our Integrative Medicine Center outpatient clinic from Sep 2012-Jan 2015. Participants completed a modified Edmonton Symptom Assessment Scale (ESAS; 0-10 scale, 10 most severe) pre- and post-massage. ESAS individual items and subscales scores of Physical Distress (PHS), Psychological Distress (PSS), and Global Distress (GSD) were analyzed. We used paired t-tests with a Bonferroni correction (i.e., p < .001) to examine pre/post massage self-reported symptoms. Results: Initial massage visits for 164 patients and 39 caregivers were analyzed. Highest symptoms burden (means) at baseline for patients were Sleep 3.93, Fatigue 3.70, and poor sense of Well-Being 3.62; for caregivers Distress 4.14, Sadness 3.43, and Sleep 3.21. Although patients reported significantly more physical symptoms (F = 27.56, P < .0001) compared to caregivers at baseline, groups did not differ in regard to psychological symptom burden (P = .75). Massage therapy was associated with significant improvements in PHS, PSS, and GSD for both patients and caregivers at P < .0001. Including participants with symptom report ≥ 1, massage resulted in a clinically significant improvement (reduction ≥ 1) in pain, fatigue, sleep, distress, dry mouth, sadness, numbness, anxiety, wellbeing for patients; pain, fatigue, distress, sadness, numbness, anxiety, wellbeing for caregivers. Regarding massage duration, there were no significant effects for 30 vs 60-min duration on pre/post ESAS difference scores. Conclusions: A single 30- or 60-minute massage session resulted in acute relief of self-reported symptoms in patients and caregivers. Further study is warranted regarding optimal massage dose and frequency.
Effect of Edmonton Symptom Assessment Scale (ESAS) on symptom data collection in a radiation oncology department.
Authors: Savla Bansi , Venkat Puja , Yu Michael
Published: February 2017

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Background: ESAS has been used to examine quality of life and symptom burden of patients undergoing cancer treatment. The purpose of this study is to examine attitudes towards ESAS among patients in a Radiation Oncology clinic in conjunction with the perspective of cancer care professionals, to establish ideal implementation of this tool to improve patient care. Methods: Routine use of ESAS in a single Radiation Oncology Department was initiated in July 2015. Six months after implementation, an anonymous, electronic survey was administered to 50 healthcare providers within this department, including attending physicians, resident physicians, advanced practice nurses, physician assistants, and registered nurses. The survey collected information regarding the value of ESAS with regards to patient care, the numerical value at which an intervention is made, which clinical interventions had been implemented due to patient-reported scores on ESAS, which patient populations benefit from ESAS administration, and how frequently ESAS should be administered. Closed and open questions were included. Results: Out of 50 providers, 36 completed the survey. Of these, 31 reported finding ESAS useful. The most common intervention was questioning the patient further about symptoms (29/36.) ESAS data are being reviewed by clinical teams and stored as part of the patient’s medical record in order to compile longitudinal data. An anonymous paper survey is currently being administered to 50 patients at the end of their radiation treatment or at their first follow-up. The survey will collect information about how well symptoms are being communicated with the clinical team, if symptoms should be added to ESAS, how often ESAS should be administered, which specific clinical interventions were provided due to ESAS, and if ESAS improved the overall patient experience. Conclusions: Our survey from the clinical team supports that ESAS is a useful modality to assess patient symptoms and to improve management for patient symptoms effectively. Our ongoing patient survey will validate these findings. These two surveys will be used to improve systematic collection of symptom data for radiation oncology patients.
Validation of the Living With Cancer (LWC) PRO tool for identifying patients (pts) with cancer appropriate for end-of-life care consultations.
Authors: Paramanathan Dhakshila , Pecora Andrew , Schultz Eric , Noh Hyun gi , DeMarco Katherine , Contreras Jose , Choi Kelly , Goldberg Stuart L.
Published: February 2017

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Background: End-of-life care (EOLC) discussions for pts with advanced malignancies are often delayed resulting in unwanted, wasteful treatment. COTA Inc has developed a 7-item PRO instrument (LWC) to facilitate identification of pts in distress. A pilot study of 433 pts at a single institution was able to determine a threshold distress score (> 28) correlating with physician assessment of appropriateness for EOLC consultation (2015 ASCO Palliative Care Symposium). Methods: LWC explores 4 personhood and clinical domains (performance status, pain, burden, and depression). Each question presents a 5-level Likert scale supplemented by a pt derived weighting of importance. The PRO was completed by 700 pts at Regional Cancer Care Associates throughout NJ between Sept 2015 and Apr 2016. The primary oncologists separately/independently classified 611 pts as appropriate to continue therapy (Group 1) and 89 pts as appropriate to curtail therapy (Group 2). Results: A score of 29 on LWC (range 0-112) was the threshold achieving optimal sensitivity (51%) and specificity (78%) in identifying pts in Group 2 (51% of pts whose oncologists felt appropriate to curtail therapy scored > 29; 78% of pts whose oncologists felt appropriate to continue therapy scored < 29). The threshold had positive predictive value 25% and 8% false omission rate (1 - negative predictive value) (25% pts scoring > 29 should be in Group 2; 8% scoring < 29 should be in group 2). A score 29 was 2.3 times more likely in pts belonging to Group 2 (likelihood ratio), and was a predictor of physician category (logistic regression p < 0.0001). LWC had a Cronbach’s alpha coefficient 0.85, indicating internal consistency and ability to measure a single latent construct. 3 questions (Performance Status, Wants, and Lack of Pleasure) contained the most information (estimate the latent trait with precision) and had high discrimination parameters (discriminate between pts lacking latent trait and displaying latent trait). Conclusions: The LWC instrument is able to identify cancer pts for whom EOLC discussions may be appropriate. A study to determine the correlation between the threshold score, EOLC consultation rate and overall survival is underway.
Psychosocial distress screening in the health care safety net.
Authors: Albert Margot , Cimino Theora , Kinderman Anne , Safier Leslie , Harris Heather A.
Published: February 2017

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Background: Recognizing that psychosocial distress (PSD) is underestimated in patients with cancer, the Commission on Cancer mandated screening using a validated tool. Studies of PSD screening exist, but none to date in a diverse, multicultural safety net setting where patients face challenges such as homelessness, mental illness, and substance abuse, which may augment PSD. Methods: We performed a retrospective cohort study of patients with cancer offered PSD screening during 2015. Overall distress scores and problems in each domain were analyzed. Chart review identified potential predictors of distress including age, gender, race, language, housing, psychiatric illness, substance abuse, and cancer stage. Results: Of 177 eligible patients, 113 (64%) completed screening. The most common reasons patients were not screened were refusal, too symptomatic (physically or emotionally), or language barriers. Of screened patients, 40.7% were female, 57.5% male, and 1.7% transgender. 31% were Caucasian, 27% Asian/Pacific Islander, 25% Hispanic, and 17% African American. 35% were non-English speaking. 29% had history of mental illness and 34% of substance abuse. 23% were marginally housed or homeless. 63% reported moderate to severe levels of PSD as defined by the NCCN as ≥ 4. Patients with mental illness were nearly twice as likely to report PSD ≥ 4 (p = 0.012) and had higher mean PSD scores (5.78 vs. 4.03, p = 0.002). English speaking patients had a mean PSD score of 5.01 compared to 3.6 and 3.2 for Spanish and Chinese speaking patients, respectively (p = 0.02 for English v. Chinese) and more domains causing PSD (p = 0.028 for English v. Chinese). Lack of stable housing also correlated with more domains causing PSD (p = 0.05). Conclusions: This proved to be an ethnically diverse cohort with high rates of mental illness, substance abuse, and homelessness, with the majority reporting moderate to severe distress. Even with a small cohort, English language and mental illness were significant predictors of PSD, and housing status correlated with more domains contributing to PSD. Several other variables trended toward significance, suggesting a larger cohort may be needed to determine if additional characteristics predict higher levels of PSD.
Patient-specific meta-analysis (MA) of two validation studies to predict pathologic outcomes in prostate cancer (PCa) using a 17-gene genomic prostate score (GPS).
Authors: Cooperberg Matthew R. , Brand Timothy C. , Simko Jeff , Sesterhenn Isabell , Zhang Nan , Crager Michael , Maddala Tara , Lawrence H. Jeffrey , Febbo Phillip G. , Srivastava Shiv , Chan June M. , Cullen Jennifer , Carroll Peter
Published: February 2017

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Background: We validated a biopsy-based assay as a predictor of PCa aggressiveness in two independent patient cohorts. Using GPS with NCCN risk group, the test provides an estimate of likelihood of favorable pathology (LFP) in low-intermediate risk PCa based on data from the first validation study. The second study re-confirmed the association between GPS and LFP. We combined information from both studies to provide more precise estimates of LFP, and examined predictive models using GPS with other clinical risk tools. Methods: Patient-specific MA provides precision-weighted predictions for individual patients using data from multiple studies (Crager and Tang, J. Appl. Stat. 2014). MA was performed on the two validation studies (732 patients total) using GPS (scale 0-100) with CAPRA score, NCCN risk group, or AUA/EAU risk group as predictors of LFP (Gleason score 3+3 or 3+4, organ-confined disease). Decision curves were calculated using the MA risk estimates. Results: MA provided more precise estimates of LFP with narrower confidence intervals (CIs) than either study alone (median width 24% narrower than the smaller of the two individual study CIs). GPS added significant predictive value for LFP to each of the 3 clinical classifiers. A model utilizing GPS and CAPRA provided the most risk discrimination. In decision-curve analysis, greater net benefit was shown when combining GPS with each clinical classifier compared with the clinical classifier alone. Over a wide range of threshold probabilities, incorporation of GPS would be expected to lead to fewer treatments of patients with favorable pathology without increasing the number of patients with adverse pathology left untreated. The proportion of men with MA-estimated LFP > 80% was 31% with GPS and CAPRA, and 23% with GPS and NCCN risk group; 11% were identified with LFP > 80% using NCCN risk group alone. Conclusions: Patient-specific MA of two independent studies provided more precise risk estimates reflecting the complete body of evidence. GPS adds predictive value to three clinical risk tools. The MA-estimated LFP identified more patients with an LFP > 80% than identified by clinical classifiers alone.
Intraductal carcinoma and cribriform architecture as novel prognostic factors in patients with prostate cancer treated with dose-escalated radiotherapy.
Authors: Murgic Jure , Berlin Alejandro , Chua Melvin , Pintilie Melania , Bristow Robert G. , van der Kwast Theodorus
Published: February 2017

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Background: Intraductal carcinoma (IDC) and cribriform architecture (CA) represent distinct pathohistological variants of high-grade prostate cancer associated with aggressive disease and poor clinical outcome. We evaluated impact of IDC and/or CA (IDC/CA) as a prognostic marker in patients with prostate cancer who underwent contemporary image-guided, dose-escalated, intensity-modulated radiotherapy (IMRT). Methods: Radiotherapy and clinical records of 379 patients with localized prostate cancer treated from 2005 to 2012 with prostate IMRT with 78 Gy in 39 fractions were retrospectively reviewed. Original diagnostic prostate biopsy slides were centrally reviewed by an expert genitourinary pathologist and scored for presence of IDC/CA. The impact of IDC/CA and other pre-treatment and treatment-related factors on biochemical relapse-free survival (BRFS) was evaluated. Results: IDC/CA was present in 19.3% of patients. After median follow-up of 56 months, 39 (10.3%) and 10 (3.6%) patients experienced biochemical failure and distant metastasis, respectively. On univariate analysis, the presence of IDC/CA was associated with decreased BRFS (HR 4.1 (95% CI: 2.2-7.8), p < 0.0001) and metastasis-free survival (HR = 4.7 (95% CI: 1.4-15.6), p = 0.013). On multivariate analysis, IDC/CA was associated with decreased BRFS (HR = 2.3 (95% CI: 1.2-4.7), p = 0.02) together with NCCN risk group (overall p = 0.0004), Gleason score (overall p = 0.016) and percent of positive biopsy cores (HR = 5.78 (95% CI: 1.4-23.9), p = 0.015). Within intermediate risk patients, presence of IDC/CA was associated with decreased BRFS (HR = 3.3 (95%CI: 1.5-7.1), p = 0.031) and was able to further stratify GS 4+3 patients (HR = 4.5, (95% CI: 1.6-13.0), p = 0.0045). Conclusions: The presence of IDC/CA in the prostate biopsy has negative prognostic impact in patients treated with dose-escalated radiotherapy. Furthermore, the prognostic significance of IDC/CA, even among unfavorable intermediate-risk patients, suggests that these pathological features should be considered in existing risk stratification tools for this patient group.
Focal HIFU (high intensity focused ultrasound) treatment of unilateral localized prostate cancer: Hemiablation strategy—A prospective French multicentric study with 111 patients.
Authors: Pasticier Gilles , Crouzet Sebastien , Rouviere Olivier , Mege-Lechevallier Florence , Tonoli-Catez Helene , Chapelon Jean-Yves , Rischmann Pascal , Gelet Albert
Published: February 2017

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Background: Up to a third of patients with localized prostate cancer (LPCa) have unilateral disease that may be suitable for a treatment of one lobe. Our aim was to evaluate the ability of HIFU to achieve a local control of the tumor in patients with unilateral LPCa. Methods: The French Urological Association (AFU) conducted a multi-institutional study, to evaluate hemi-ablation with HIFU as a primary treatment for patients >50 years, T1C or T2A, PSA<10ng/ml, Gleason ≤7 (3+4), and unilateral disease. 111 patients were treated: mean age 64.8 ±6.18 years, mean PSA 6.23±2.5 ng/ml. Gleason sum was ≤6 in 73.9% and 7 in 26.1%.primary outcome was the negative biopsy rate. Secondary outcomes were genitourinary side effects measured using validated questionnaires. The tumor was localized using MRI followed by random and targeted transrectal biopsies. Only the pathological prostate lobe was treated using HIFU. Results: The PSA nadir value was 1.87±1.49 ng/ml and the PSA at 12 months was 2.49±2.1 ng/ml (median 1.89). Ninety patients out of 101 (89%) in whom control biopsies were performed, had histological absence of significant disease (Gleason 7 or presence of cancer core length >3mm): treated side 5%, untreated side 5.9%. However 32.6% of men had persistent cancer of any threshold. Additional therapies were proposed in 33 patients (29,7%): active surveillance (16 patients), Redo-HIFU (8 patients), external beam radiation therapy (3 patients), radical surgery (6 patients). The RTFS (radical treatment free survival rate defined as absence of whole gland therapy) at 2 Years was 89%. At 12 months pad free continence was preserved in 103/106 (97%) and erectile function (IIEF5 score ≥16) was preserved in 40 patients out of 51 patients (78%). Conclusions: HIFU hemi ablation strategy allows an encouraging local control of the cancer has minimal side effects compared with standard whole gland treatments and allows additional therapies if necessary. Clinical trial information: HIFU/AFU/08.06.
Utilization of radiotherapy for prostate cancer according to urologists’ practice patterns.
Authors: Williams Stephen Bentley , Huo Jinhai , Smith Benjamin D. , Hoffman Karen E.
Published: February 2017

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Background: Physician practices that offer ancillary medical services may refer their patients for such services, a process known as self-referral. Self-referral for radiation therapy according prostate cancer risk and cost of care is not known. We evaluated how utilization and cost of care differ for men diagnosed with prostate cancer in a self-referring urologic practice (SRP) compared to a traditional urologic practice. Methods: 17,982 men 66 years and older diagnosed with localized prostate cancer from 2006 to 2009 were identified from the Texas Cancer Registry. Disease was classified as favorable if low-grade and clinical T1 or T2. The diagnosing urologist was classified as being affiliated with a SRP if their practice owned a linear accelerator. Multilevel logistic regression models evaluated the odds of receiving a specific type of treatment adjusted for diagnosis year, age, comorbidities, race/ethnicity, income, education, clinical tumor stage, and tumor grade. Cost of care was calculated from Medicare expenditures within 12 months of diagnosis. Results: Diagnosis in a SRP increased from 2.2% of prostate cancers in 2004 to 24.5% in 2009 (p< 0.001). Men diagnosed in SRPs were more likely to receive upfront treatment (vs. watchful waiting/active surveillance) than men diagnosed by traditional practices (92.7% vs. 89%; AOR 1.61, p<0.001) and were more likely to be treated with external beam radiation (47.4% vs. 34.1%; AOR 1.59, P<0.001). This persisted for both favorable and unfavorable risk cancer. Men diagnosed in SRPs were more likely to receive upfront treatment (favorable: 92.9% vs. 87.1%; AOR 1.89, p<0.001; unfavorable: 97.9% vs. 95.0%; AOR 2.07, p=0.002) and more likely to be treated with EBRT (favorable: 41.2% vs. 31.1%; AOR 1.45, p=0.002; unfavorable: 49.0% vs. 38.1%; AOR 1.53, p<0.001). Median annual prostate cancer care cost was $2,460 (95% CI $1,663-$3,368) higher for men diagnosed by SRPs. Conclusions: Older men diagnosed with prostate cancer in SRPs are more likely to undergo upfront treatment and to receive radiation treatment. This may increase appropriate treatment of unfavorable disease but contribute to overtreatment of favorable disease.
Risk factors for disease progression after post-prostatectomy salvage radiation: Long-term results of a large institutional experience.
Authors: Rodin Danielle , Andersen Lars Wiuff , Buscariollo Daniela , Drumm Michael , Clayman Rebecca Helen , Galland Sigolene , Eidelman Alec , Feldman Adam S. , Lee Richard J. , Dahl Douglas M. , McGovern Francis J. , Olumi Aria F. , Niemierko Andrzej , Shipley William U. , Zietman Anthony L. , Efstathiou Jason A.
Published: February 2017

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Background: Salvage radiotherapy (SRT) has been successfully used to treat recurrent prostate cancer following radical prostatectomy (RP). The objective of this study was to identify risk factors for disease progression post-SRT. Methods: Retrospective review of 719 consecutive patients who had RP and received post-operative radiation (adjuvant/SRT) for recurrent prostate cancer from 1992-2013. Disease progression was defined by a prostate specific antigen (PSA) ≥0.2 ng/ml, local recurrence, nodal failure, or distant metastases. Analysis was restricted to patients treated after 2000, when the PSA detectability threshold decreased to 0.2. Univariable and multivariable Cox regression analysis with backwards selection was performed with the following variables: demographics (age, race), pathological features (Gleason score, positive margins, pT-stage), surgery type, radiation details, hormone therapy, and pre-SRT PSA. Secondarily, we included PSA velocity and doubling-time as continuous variables in the model. Results: 384 patients received SRT after 2000, of which 152 had disease progression, with a median time to recurrence of 6.2 years (95% CI 4.1-7.6 years). Multivariable analysis results are reported in the Table. Gleason score, T-stage, seminal vesicle invasion, and pre-SRT PSA were associated with progression. Pre-SRT PSA ≤ 0.3 conferred the lowest rate of disease progression. In a secondary model, PSA kinetics was evaluated in which doubling-time was associated with progression (HR 0.98 per month increase, 95% CI 0.96-1.00; p=0.03). Conclusions: The lowest rate of disease progression was found amongst patients treated with a PSA ≤ 0.3. A shorter DT may also be a useful predictor of disease progression after SRT. [Table: see text]
Genomic predictors of biochemical failure following radical prostatectomy.
Authors: Aneja Sanjay , Yu James B. , Glazer Peter
Published: February 2017

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Background: Although clinical correlates can help predict biochemical failure (BF), genomic correlates have yet to be identified. We hypothesized there would exist genomic profiles in patients who experience BF after radical prostatectomy (RP), for whom aggressive regional therapy may be more appropriate. Methods: Genes of interest were identified using the 25 most commonly mutated genes from the COSMIC dataset. The Cancer Genome Atlas (TCGA) was used to study normalized microarray gene expression data for patients who underwent RP for treatment of Gleason 7-10, T1/T2 N0 prostate adenocarcinoma. BF was considered PSA > 0.1 following prostatectomy. Clinical data of interest included age, pre-treatment PSA, Gleason score, pathologic T stage, and country of origin. A multi-level hierarchical logistic regression model clustered with random effects by pathologic T stage and country of origin was built to identify predictors of BF. Variances were used to estimate how genomic differences explained differences in BF. Results: We identified 296 patients with T1/T2 N0 prostate adenocarcinoma who underwent RP. Median age was 60 with a median follow up of 2.3 years. 59% (n = 177) had Gleason 7 disease and 54% (n = 154) had T1 disease. 40.8% (n = 121) of patients had BF following RP. After adjusting for clinical covariates, 4 genes were associated with differences in BF. Specifically, increased RNA expression of E2F3 (OR 1.11 p < .001), CTNNB1 (OR 1.49, p = .002), and AR (OR 1.21, p < .001) were seen in patients who experienced BF. Expression of TP53 (OR 0.75, p < .001) and Gleason 7 disease (OR 0.62 vs. Gleason 8-10, p < .001) were associated with decreased likelihood of BF. Clustering by pathologic T stage accounted for 10% of variance in BF indicating that the 4 genes augment clinical patient characteristics. Conclusions: Genomic data augments pre-treatment clinical data in the stratification of patients undergoing RP. RNA expression of E2F3, CTNNB1, AR and TP53 is associated with differences in BF following RP. Clinically, these genes could aid in identifying patients who may benefit from more aggressive therapy. Further studies of the relationship between these genes and the development of prostate cancer could aid in future targeted therapies.
Phase II study of lovastatin to prevent rectal injury from radiation therapy for prostate cancer.
Authors: Anscher Mitchell Steven , Chang Michael G. , Moghanaki Drew , Rosu Mihaela , Mikkelsen Ross , Holdford Diane , Skinner Vicki , Grob B Mayer , Sanyal Arun J. , Mukhopadhyay Nitai
Published: February 2017

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Background: Late radiation induced rectal injury remains an issue. Large population based studies indicate an incidence of at least 15%. Statins have been shown to reduce the risk of late radiation injury in animal models. The purpose of this study was to prospectively test lovastatin as a potential protector against radiation induced rectal injury, particularly bleeding. Methods: Eligible patients included men with adenocarcinoma of the prostate who were to be treated with radiation therapy with curative intent. Patients receiving primary radiation therapy (external beam alone, brachytherapy alone, or a combination of both) or post-prostatectomy radiation were eligible, as long as the minimum dose to the rectum was 60 Gy. Patients began lovastatin 20-80 mg/d on day 1 of radiation. Lovastatin was continued for 1 year and patients were followed for an additional year. Patients were seen at 1, 2, 4, 6, 9, 12, 18, 21 and 24 months after treatment. At each follow-up, they were assessed for GI, GU and erectile complications using both patient reported (IIEF, EPIC) and physician reported (CTCAE v3) instruments. The primary endpoint of the study was the incidence of rectal bleeding at 24 months (Grade 2 or higher). Results: From April 2007 through May 2013, 73 patients were enrolled. 21 patients either withdrew or were removed from the study due to noncompliance with the lovastatin regimen or toxicity from the drug. Patients who withdrew or were removed were replaced, in order to achieve the target number of 53 evaluable patients with complete 2-year follow-up. A total of 50 patients are evaluable. All but 2/50 evaluable patients achieved the 24-month follow-up goal. At 24 months, there were a total of 4 patients with rectal bleeding attributable to radiation; 3 were grade 2 and 1 was grade 3 (4/48=8%). Conclusions: The incidence of rectal bleeding at 2 years in this population of patients receiving lovastatin during and after radiation therapy for prostate cancer was less than expected based on historical controls. These data suggest that statins may be useful to protect patients from radiation induced rectal injury. Clinical trial information: NCT00580970.
Neurovascular bundle-sparing radiotherapy for prostate cancer using MRI-CT registration: A dosimetric feasibility study.
Authors: Cassidy Richard John , Yang Xiaofeng , Liu Tian , Nour Sherif , Jani Ashesh B.
Published: February 2017

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Background: Sexual dysfunction after radiotherapy for prostate cancer remains an important late adverse toxicity. The neurovascular bundles (NVB) that lie postero-laterally to the prostate are typically spared during prostatectomy, but in traditional radiotherapy planning they are not contoured as an organ-at-risk with dose constraints. Our goal was to determine the feasibility in sparing the NVB while still delivering adequate dose to the prostate. Methods: Twelve consecutive patients with intermediate- or high-risk prostate cancer (with no gross disease within 2mm of either NVB) who were treated with external beam radiotherapy, with the same primary PTV margins, to a dose of 79.2 Gy were evaluated. Pelvic MRI and simulation CT scans were registered using dedicated software to allow for bilateral NVB target delineation on T2-weighted MRI. A volumetric modulated arc therapy (VMAT) plan was generated using the NVB bilaterally with 2mm margin as an organ to spare (with goal of reducing V70Gy by 30%) and compared to the patient’s delivered plan. Dose-volume histogram (DVH) endpoints for NVB, rectum, bladder, and PTV79.2 were compared between the two plans using a 2-tailed paired t-test. Results: The V70 for the NVB was significantly lower on the NVB sparing plan (p <0.01), while rectum and bladder endpoints were similar. Target V100% was lower (but still > 95%), and V105 was higher for the NVB Sparing plans (p <0.01). The table summarizes the DVH comparisons between the two plans. Conclusions: “NVB-sparing” radiotherapy is dosimetrically feasible using VMAT technology; target coverage is acceptable without increased dose to other normal structures, but with higher target dose inhomogeneity. The clinical impact of “NVH-sparing” radiotherapy is currently under study at our institution. [Table: see text]
Expectant management of veterans with early-stage prostate cancer.
Authors: Filson Christopher Paul , Shelton Jeremy B. , Tan Hung-Jui , Kwan Lorna , Skolarus Ted A. , Saigal Christopher , Litwin Mark S.
Published: February 2017

13

Background: We evaluated the association between various factors and the use of expectant management (EM) among patients with prostate cancer treated in the Veterans Health Administration. Methods: We identified men diagnosed with prostate cancer in 2008. Outcome of interest was use of EM captured through an in-depth chart review. We fit multivariable regression models to examine associations between EM use and patient demographics, cancer severity, and facility characteristics. We then assessed regional variation across 52 facilities by generating predicted probabilities for receipt of EM. Results: Among our analytic cohort (n=6,540), 34% of men were treated expectantly. EM was more common among patients 75 and older (40% vs. 27% under 55 years, OR 2.57) and with low-risk tumors (49% vs. 20% high-risk, OR 5.35). There was no association between patient comorbidity and receipt of EM (p=0.90) (Table). There were also no significant associations between facility factors and receipt of EM (all p>0.05). Among ideal EM candidates, receipt of expectant management varied considerably across individual facilities (0 – 85%, p<0.001). Conclusions: Patient age and tumor risk were both more strongly associated with the use of expectant EM than patient comorbidity. Though its appears appropriate broadly, there was variation in EM between hospitals, apparently not attributable to facility factors. Research determining the basis of this variation—with a focus on providers—will be critical to help optimize prostate cancer treatment for veterans. [Table: see text]
Gleason <6 (G6) prostate cancer (PC) at radical prostatectomy (RP): Does a high-risk setting truly exist? A recursive partitioning analysis (RPA).
Authors: Smith Mark C , Russo James Kyle , Tracy Chad , Mitchell Darrion , Mott Sarah , Buatti John Michael , Watkins John Morgan
Published: February 2017

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Background: G6PC is associated with low rates of PSA failure (bF) after primary treatment. The present study seeks to determine whether a "high-risk" subpopulation of G6PC with lower PSA relapse-free survival (bRFS) may be identified within a large population of men with mature follow-up who underwent RP for curative-intent. Methods: Patients were retrospectively identified for inclusion by cT1-2 PC with PSA <30 at diagnosis, managed by RP alone, with final pathology demonstrating G6PC. Exclusion criteria were: pT3b or pN1, pre- or post-RP (adjuvant) radiotherapy (RT) or hormone therapy, or PSA follow-up (<12 months). The Kaplan-Meier method was employed for survival probability estimation. RPA by conditional inference analysis was applied to identify variables associated with bF. Results: From 2003-2009, 284 patients were eligible for this analysis. The median age was 60 yrs (range, 44-76), 233 (82%) were T1c, and median PSA was 5.3 (92% <10 ng/dL). The median biopsy to RP interval was 50 days (11-410, with 97% <180 days). Eighty patients (28%) had a positive margin (M+). At a median follow-up of 92.6 months (16.9-160.9, with 45% followed >8 years), 32 patients (11%) had bF, with estimated 5/8yr bRFS rates of 91%/89%. Univariate analysis identified M+, EPE, detectable initial post-RP PSA (at <26wks post-RP), longer biopsy to RP interval, and smaller RP specimen volume as significantly associated with bF, with M+ and longer biopsy to RP interval significant at multivariate analysis. RPA identified only M+ as a stratification factor, with 5/8yr bRFS estimates of 79/74% for M+ vs. 96/95% for M-. No other factors permitted further substratification of risk. Of note, 7 of 12 patients who underwent salvage RT alone remained disease-free at last follow-up, including 7 of 8 whose highest pre-salvage RT PSA was <0.6. Conclusions: G6PC managed by RP alone is generally associated with high rates of bRFS; however, in the M+ setting, irrespective of other clinical factors, early bF rates >20% are observed. Adjuvant RT should be considered in G6PC M+ cases; however, close surveillance with early salvage RT may be a reasonable alternative.
High-intensity focused ultrasound (HIFU) as salvage therapy for radio-recurrent prostate cancer: Predictors of disease response.
Authors: Dason Shawn , Allard Christopher Brian , Hoogenes Jen , Orovan William , Shayegan Bobby
Published: February 2017

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Background: Some patients with localized radio-recurrent prostate cancer (PCa) may have long-term recurrence-free (RFS) survival with salvage high-intensity focused ultrasound (HIFU). In this study, we describe our previously unreported oncologic outcomes and predictors of disease response after salvage HIFU. Methods: Participants were prospectively enrolled in this study from January 2005 to December 2014 if they had localized radio-recurrent prostate cancer. Participants had to meet both biochemical (PSA nadir+ 2ng/ml) and histologic (positive biopsy) definitions of recurrence. Study exclusion criteria included the receipt of prior salvage therapy, presence of metastastatic disease, and receipt of ADT in the 6-months prior to enrollment. Participants were treated with a single session of whole-gland HIFU ablation with the Ablatherm device (EDAP, France). The primary endpoint of this study was RFS, defined as a composite endpoint of PSA progression (PSA nadir + 2 ng/ml), receipt of any further salvage therapy, receipt of ADT, clinical progression, or death. Kaplan-Meier survival analysis was used to determine the primary end-point and stratifications were used to determine the significance of 6 pre-specified predictors of improved RFS (undetectable PSA nadir, low TRUS biopsy grade, >3 TRUS biopsy cores positive, pre-HIFU PSA<4ng/ml, receipt of prior ADT and presence of pre-HIFU palpable disease). Survival analysis was performed on participants with a minimum of 1-year follow-up. Results: Twenty-four participants were eligible for study inclusion with a median follow-up of 31.0 months. Median PSA at study entry was 4.02 ng/ml. Median time to PSA nadir was 3 months after treatment and median post-HIFU PSA nadir was 0.04 ng/ml. 2-year and 5-year RFS were 66.3% and 51.6% respectively. An undetectable PSA nadir was the only significant predictor of improved RFS (HR 0.07, 95% CI 0.02-0.29, log-rank P<0.001). No participants developed a rectourethral fistula. Conclusions: Salvage HIFU allows for disease control in select patients with localized radio-recurrent prostate cancer. An undetectable PSA nadir serves as an early predictor of disease response.