bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of triple antiemetic therapy (palonosetron, dexamethasone, aprepitant) for chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based, moderately emetogenic chemotherapy.
Authors: Miya Toshimichi , Kobayashi Kunihiko , Hino Mitsunori , Ando Masahiro , Takeuchi Susumu , Seike Masahiro , Kubota Kaoru , Gemma Akihiko
Published: February 2017

226

Background: Chemotherapy-induced nausea and vomiting (CINV) is a major adverse toxicity of cancer chemotherapy. Recommended treatments for prevention of CINV vary among guidelines, and optimal care for CINV caused by moderately emetogenic chemotherapy has not been established. This study assess efficacy and safety of triple antiemetic therapy consist palonosetron, dexamethasone and aprepitant for carboplatin-based chemotherapy. Methods: Chemotherapy-naïve patients with lung cancer scheduled for a first course of a carboplatin-containing regimen formed the study cohort. Patients were pretreated with antiemetic therapy consist palonosetron (0.75 mg, i.v.) and dexamethasone (9.9 mg, i.v.) on day 1, and aprepitant (125 mg, p.o.) on day 1 followed by 80 mg on days 2 and 3. Primary endpoint was the proportion of patients who did not experience vomiting and did not require rescue medication (complete response (CR)) in the acute phase (0-24 h), late phase (24-168 h) and overall. Secondary endpoint was the proportion of patients who experienced no vomiting episodes and no more than mild nausea without the need for rescue medication (complete control (CC)). Results: Prevalence of a CR during the acute phase, delayed phase, and overall was 100%, 91.9% and 91.9%, whereas that of CC was 100%, 84.4% and 84.4%, respectively. Most common adverse events were mild constipation; severe adverse events related to antiemetic treatment were not observed. Prevalence of a CR during the acute phase, delayed phase, and overall was 100%, 91.9% and 91.9%, whereas that of CC was 100%, 84.4% and 84.4%, respectively. Most common adverse events were mild constipation; severe adverse events related to antiemetic treatment were not observed. Conclusions: Triple antiemetic therapy comprising palonosetron, dexamethasone and aprepitant shows excellent effects in preventing CINV in patients receiving a carboplatin-containing regimen. Clinical trial information: UMIN000017877.
Toxicities of the anti-PD-1 immune checkpoint antibody nivolumab in the acute inpatient setting.
Authors: Brito-Dellan Norman
Published: February 2017

227

Background: Knowledge of immune-system regulation led to the discovery of immune checkpoints molecules, which have demonstrated anti-tumor activity across various malignancies. These advances represent a new set of challenges for clinicians, including non-oncologists treating the cancer patient, who must develop a working knowledge of the mode of action of these agents, their unique response kinetics, and how to diagnose and effectively manage their toxicities. Nivolumab is a monoclonal immune checkpoint antibody that binds to the PD-1 receptor on T-cells, blocking PD-1 pathway-mediated anti-tumor immune response inhibition. Methods: Review of current literature and analysis of 3 cases of patients with Nivolumab-related toxicities at a major cancer center. Results: Case #1: 74 years-old female with NSCLC who was started on nivolumab after developing disease progression with various regimens. Nivolumab was held 4 months later due to development of erythematous, edematous papules and plaques, with overlying ulcerations and crust in forearms, thighs and trunk. Also, paronychias and loss of nail beds in both great toes. She developed no new lesions after discontinuation of immunotherapy. Case #2: 71 years-old male with right lung NSCLC, started on Nivolumab after evidence of disease progression after completion of carboplatin/paclitaxel. Four months later developed grade 2 Nivolumab-induced pneumonitis; this was withheld and ultimately discontinued due to persistent pneumotoxicity in spite of corticosteroids. Case #3: 41 years-old male with synchronous right lung ALK-positive adenocarcinoma, on crizotinib, and left lung squamous cell carcinoma, on nivolumab. He developed nivolumab-induced ANCA-negative glomerulonephritis, which was discontinued while continuing the crizotinib. His renal function normalized 3 months later, with GFR going from 14 to 122. Conclusions: Most adverse events with the anti-PD-1 agent Nivolumab are generally reversible after discontinuation of therapy, yet some high-grade immune-related adverse events require management with corticosteroids and other immune modulating agents. Further research is needed.
OAMs at the end: The end of the beginning or the beginning of the end?
Authors: Hargadon Annemarie P , Galligan Barbara Marie , Shah Chintan , Zhao Iris Chen , Paciotti Brian , Fairman Nathan , Tran Quy
Published: February 2017

229

Background: In 2001, after three months of review, the FDA approved the oral anticancer agent imatinib, making it the fastest approval in FDA history. Since then, the FDA has approved over 40 oral anti-cancer medications (OAMs) and the number continues to rise, transforming cancer care, improving survival in specific cancers and providing new hope. However, the rapid development of OAMs has produced uncertainty over the best use of these new medications, particularly at the end of life. ASCO guidelines recommend against prescribing intravenous chemotherapy within two weeks of expected death, but no such guidelines have yet been developed for OAMs. We describe one institution’s experience in prescribing OAMs at the end of life. Methods: An interdisciplinary team of pharmacy, oncology and palliative care specialists undertook an IRB-approved retrospective electronic health record review of patients who died between 1/1/2012 and 12/31/2015 and had been on one of seven oral anti-cancer medications (erlotinib, sunitinib, pazopanib, crizotinib, sorafenib, afatinib, regorafenib). From this cohort, descriptors such as diagnosis, stage, prior lines of therapy, ECOG, BMI and albumin were extracted. Results: There were at total of 62 patients who were on at least one of the seven drugs and died during the specified time period. Of these 62 patients, only 2 (3%) had a first prescription for an OAM in the last 30 days of life. Over 90% of the patients that were not prescribed an OAM within 30 days of death were patients with Stage IV disease with a median age of 66 and had an average of 3 prior lines of therapy. Consistent with prognostic models, these patients all had declining albumin, BMI and performance status. Conclusions: Oncologists at this institution rely on prognostic data to gauge when to recommend stopping IV chemotherapy before the last two weeks of life. Extrapolating from ASCO guidelines on the use of IV chemotherapy, these oncologists generally refrain from prescribing OAMs in the last 30 days of life. Unless strong data shows definitive benefit for the use of OAMs, we propose ASCO guidelines recommend not using OAMs during the last two weeks of life.
Characteristics and outcomes of psychology referrals in palliative care.
Authors: Ann-Yi Sujin , Bruera Eduardo , Agosta Monica T. , Guzman Diana , Najera John M. , Raznahan Monica , Williams Janet L. , Carmack Cindy L.
Published: February 2017

230

Background: Despite high distress, a small percentage of cancer patients are referred for psychological care. MD Anderson’s interdisciplinary Palliative Care team recruited 2 clinical psychologists in 9/2013. The demand for services exceeded capacity; thus a 3rd psychologist and 3 counselors were added in 6/2015. Methods: Retrospective review of 2827 unique patients (6451 total contacts) from 9/1/2013 to 2/29/2016, including billable (psychologists) and non-billable (counselors) services. Results: Psychologists saw 1958 unique patients (4987 contacts): 1662 (85%) inpatients and 296 (15%) outpatients. Mean inpatient and outpatient session length was 37 (SD = 15) and 51 (SD = 19) minutes, respectively. 865 (44%) patients had 1 session, 507 (26%) had 2, and 585 (30%) had 3 or more. At first visit, DSM-5 diagnoses were: 1681 (86%) adjustment disorders and 226 (12%) major mood or anxiety disorders. Most first visits included assessment (N = 1666; 85%); other services were also provided: 1545 (79%) supportive expressive counseling; 300 (15%) family counseling; 114 (6%) cognitive-behavioral therapy (CBT); and 40 (2%) relaxation skills. From 6/2015-2/2016, counselors saw 869 unique patients (1464 contacts): 759 (87%) outpatients, 99 (11%) inpatients, and 11 (1%) outreach through web-based video or phone. Mean session length for outpatient, inpatient, and outreach was respectively, 37 (SD = 17), 34 (SD = 18), and 17 (SD = 8) minutes. 560 (64%) patients had 1 session, 166 (19%) had 2, and 143 (17%) had 3 or more. Services at first visit included: 994 (93%) supportive expressive counseling; 654 (61%) assessment; 139 (13%) relaxation skills; 99 (9%) CBT; and 73 (7%) acceptance and commitment therapy (ACT). Conclusions: The 128% increase in psychology services after expanding providers underscores the value placed by the Palliative Care team. With the majority receiving only 1 session, results indicate the need to improve screening for earlier referral, allowing for more sophisticated services such as CBT and ACT, which are most effective for major mood or anxiety disorders and may prevent adjustment disorders from progressing to greater clinical distress. Our new efforts at outreach could also enhance access and types of services provided.
Effect of early integrated palliative care on family caregivers (FC) outcomes for patients with gastrointestinal and lung cancer.
Authors: El-Jawahri Areej , Jackson Vicki A. , Greer Joseph A. , Pirl William F. , Park Elyse R. , Back Anthony , Muzikansky Alona , Kamdar Mihir , Rinaldi Simone , Jacobsen Juliet , Fishbein Joel , Eusebio Justin , VanDusen Harry , Nipp Ryan David , Ryan David P. , Temel Jennifer S.
Published: February 2017

234

Background: Patients with newly diagnosed advanced cancers who receive early palliative care (PC) integrated with oncology care report improvement in their quality of life (QOL) and mood. While a telephone-based psycho-educational intervention for FC decrease depression, the impact of early, integrated outpatient PC models on FC outcomes remains unknown. Methods: We conducted a randomized trial of early PC integrated with oncology care versus oncology care alone for newly diagnosed patients with incurable lung and gastrointestinal cancers and their FC. Eligible FC were relatives or friends who would likely accompany the patient to clinic visits. FC were eligible to enroll up to 4 weeks after patient enrollment. The intervention entailed at least monthly patient visits with PC from the time of enrollment. FC were not required to attend these visits. We used the Medical Outcomes Study Health Survey Short Form-36 to examine QOL and the Hospital Anxiety and Depression Scale to examine mood at baseline, weeks 12 and 24. We used the two-sample t-test to examine changes in QOL and mood from baseline to week 12 and week 24. Results: We enrolled 350 patients and 275 (78.6%) of potentially eligible FC (control n = 138, intervention n = 137) between 5/2/2011 to 7/20/2015. FC outcomes missing data rate at 12 and 24 weeks were 16.8% and 33.8% respectively. At 12 weeks, FC of patients receiving early PC reported higher vitality (1.1 vs. -3.2, p = 0.05) and social functioning (-3.0 vs. -3.8, p = 0.02), and lower depression symptoms (-0.45 vs. 0.24, p = 0.03) compared to FC of patients assigned to usual care. At 24 weeks, FC of patients assigned to early PC had lower depression symptoms (-0.37 vs. 0.28, p = 0.05), but no differences in vitality or social functioning compared to those receiving usual care. No differences in other SF-36 subscales or anxiety were noted at 12 and 24 weeks. Conclusions: Early involvement of PC for patients with newly diagnosed lung and gastrointestinal cancers leads to improvements in FC depression and aspects of QOL. This work demonstrates that the benefits of early, integrated palliative care models in oncology care extend beyond patient outcomes and positively impact the experience of FC. Clinical trial information: NCT01401907.
Spirituality, religiosity, spiritual pain, and quality of life among Latin American patients with advanced cancer (LAAdCa): A multicenter study.
Authors: Delgado-Guay Marvin Omar , Palma Alejandra , Duarte Eva Rossina , Grez Monica , Tupper Laura , Liu Diane D , Ferguson Andrea Octavia , Bruera Eduardo
Published: February 2017

246

Background: The associations between spirituality (S), religiosity (R), spiritual pain (SP), symptom, coping and quality of life (QOL) have not been well characterized in LAAdCa. The main purpose of this Multicenter study was to analyze these associations. Methods: We interviewed 325 LAAdCa at a Palliative Care clinic in Chile, Guatemala, and USA. They completed FICA (S/R assessment), ESAS–FS (including SP), PSWQ (Worry), B-COPE and B-R-COPE (coping), FACIT-sp-ex (Spiritual Well-being). Results: Median age 58 (range: 19-85), 60% women, 62% Catholic, 30% Christian not Catholics, and 2% with no religion. 97% of LAAdCa considered themselves spiritual and 89% religious, median 7(IQR: 5-10) and 7(5-9) respectively. Median Importance of S/R in life (score 0 = none, 10 = very important) was 10 (IQR:8-10). The frequency and associations among the importance of S/R and different items were: helps them to cope with their illness (98%, r = 0.73; p < 0.0001), is a source of strength and comfort (99%, r = 0.79; p < 0.0001), and has a positive effect in physical symptoms (81%, r = 0.40; p < 0.0001), emotional symptoms (84%, r = 0.42, p < 0.0001), and helps to their caregivers to cope with pts' illness (100%, r = 0.66, p < 0.0001). 60% of LAAdCa reported that their S/R needs had not been supported by the medical team. 24% had received pastoral attention inside the hospital. 162/311 (52%) of LAAdCa reported spiritual pain (median 6; IQR: 5-8). Spiritual pain significantly correlated with worse pain (p = 0.02), fatigue (p = 0.0002), depression (p < 0.0001), anxiety (p < 0.0001), Financial distress (p < 0.0001), worry (p < 0.001), behavioral disengagement (p = 0.01), FACIT-sp-Ex (p = 0.0002), negative religious coping strategies (p < 0.0001), caregiver’s SP (p = 0.02), caregiver’s depression (p < 0.0001), caregiver’s anxiety (p = 0.0007), and worse caregiver’s QOL (p = 0.001). Conclusions: Majority of LAAdCa considered themselves spiritual and religious. S/R help to deal with their illness and correlates with less emotional distress, positive coping strategies and QOL. Still more than 50% LAAdCa reported SP and their S/R needs are not totally supported by the medical team. More research is needed.
Scrambler therapy for the treatment of chronic post-mastectomy pain (cPMP) in breast cancer survivors.
Authors: Smith Thomas J. , Loprinzi Charles L. , Cheville Andrea L.
Published: February 2017

253

Background: cPMP is chronic pain in the front thorax, axilla, and/or upper half of the arm beginning after mastectomy or lumpectomy persisting > 3 months after treatment and presents with pain, allodynia and disability. cPMP occurs in half of all patients with breast cancer and is severe in 13% (Gartner R JAMA 2009). Epidural bupivacaine, memantine, gabapentin or venlafaxine may help prevent cPMP, but there are no established proven treatments. (Shen J, Up to Date 2016) Scrambler therapy (ST) is an FDA-cleared treatment for neuropathic pain supported by multiple trials in over 800 patients with cancer pain, chemotherapy induced neuropathic pain, back pain, and post herpetic neuropathy (PHN). (Majithia N JSSC 2016) Methods: We treated 2 women with cPMP with standard ST, with repeated treatment if the pain returned. ST was done with ECG pads above and below the pain for 45 minutes daily, until pain resolved, and repeated if/when pain recurred. Results: Case 1: A 60 year-old woman had bilateral mastectomy 2 years prior with cPMP like “a barbed wire bra”. Before treatment, her pain was 8, which decreased to 0-2 after 5 treatments. Her pain returned 4 months later and was successfully retreated. She resumed a more normal life and was able to taper and eventually stop her opioids. Case 2: A 56 year-old woman had deep aching cPMP for a year following chemo, Mastectomy, and RT. Her pain was 10, decreased to 0-1/10. Her pain returned 1 month later; 3 treatments reduced her pain from 4/10 to 0/10 and improved her quality of life, which lasted for several months until cancer recurrence. Conclusions: Scrambler therapy successfully treated cPMP in 2 patients with improved pain and quality of life, and enabled one patient to stop her opioids in line with new CDC guidelines. Scrambler therapy appears to hold promise, as it does in chemotherapy-induced neuropathy, failed back syndrome, PHN, low back pain and other conditions; prospective trials are indicated to further evaluate this treatment modality. [Table: see text]
The effectiveness of nutritional-sensitive approach to restore physical activity in cachexic female palliative patients: A randomized controlled trial.
Authors: Kapoor Neha
Published: February 2017

258

Background: Loss of lean body mass, body fat along with inflammation characterizes cachexia in patients with cancer. Nutrition intervention with counseling may ameliorate undernutrition and metabolic alterations. The aim of this study was to improve nutritional status and quality of life by providing nutrients dense natural food (IAtta) along with counseling. Methods: Female patients with cancerwith symptoms of cachexia were randomly distributed into placebo (n = 75) and intervention group (n = 75). Patients were recruited from the palliative clinic, Oncology department in AIIMS, New Delhi, India. In addition to nutritional counseling, patients were instructed to consume 100g nutritional supplement on daily basis with their normal dietary intake and for six months period. The intervention group received 100g of IAtta while placebo group received 100g of whole wheat flour. Body weight – BW; mid upper arm circumference - MUAC, physical activity level - PAL, quality of life – QoL domains and total body water (TBW) were assessed at baseline, three months and after six months. Study variables were analyzed using repeated-measures ANOVA and the Friedman test (P-value < 0.05; 95% confidence interval). Results: After 6 months,patients in group IAtta had significant improvement in PAL and QoL domain (global health status, p < 0.001 and fatigue, p = 0.001). Despite the decrease in BW from 43.3 ± 7.0 to 41.6 ± 5.7 Kg (p = 0.014), TBW and MUAC (p = 0.068) were maintained. Conversely, the QoL in placebo group did not improve (global health status, p = 0.74) neither their PAL. Moreover, significant increase in TBW (due to water retention) and BW (from 42.6±7.1 to 43.5±7.4 Kg, p = 0.001). Conclusions: Nutrition-sensitive approach (IAtta meal), along with nutrition counseling, improve quality of life and physical activity in female cachexia palliative patients with cancer. Clinical trial information: NCT02561143. [Table: see text]
Critical conversations in gynecologic oncology: Pilot study of communication skills training for fellows and advanced practice providers.
Authors: Lefkowits Carolyn , Bevis Kerri S. , Carey Elise , Arnold Robert , Podgurski Lisa
Published: February 2017

29

Background: Good communication is crucial to good patient care. Gynecologic oncology providers often face challenging communication scenarios, including giving serious news and discussing goals of care. Communication skills training (CST) has been shown to improve skill acquisition among providers of multiple specialties, but it has not been described in providers from gynecologic oncology or any surgical oncology specialty. Methods: We conducted a two-day CST workshop, based on the VitalTalk© model, with four faculty members (2 gynecologic oncologists and 2 palliative care physicians) and 10 gynecologic oncology provider participants (5 fellows and 5 advanced practice providers). Using didactics, demonstrations and practice sessions with simulated patients we focused on giving serious news and discussing goals of care. Pre and immediate post-workshop surveys evaluated acceptability of the workshop, perceived impact of preparedness to address challenging communication scenarios and anticipated impact on clinical practice. We compared pre and post-workshop prevalence of score of 4 or 5 out of 5 on a Likert scale for preparedness to handle 14 challenging communication scenarios. Results: Participants reported statistically significant increase in preparedness to handle 13 out of 14 challenging communication scenarios. Among those 13 topics, magnitude of improvement in proportion of participants rating preparedness 4 or 5 out of 5 ranged from 40-100% (all p < 0.05). All participants would recommend the course to others and all strongly agreed that this training should be required of all gynecologic oncology clinicians. Conclusions: Participants felt strongly that the workshop provided high quality education relevant to their practice. As a result of the workshop, participants reported statistically significantly increased preparedness to handle challenging communication scenarios. CST is feasible and has high perceived effectiveness for clinicians in the primarily surgical oncologic specialty of gynecologic oncology.
Decision support needs-assessment in newly diagnosed malignant glioma.
Authors: Ronan Lara Kunschner , Fadul Camilo E. , Wishart Heather
Published: February 2017

33

Background: Diagnosis of malignant glioma is catastrophic and standard treatment options remain non-curative. Patients are not guaranteed a good outcome, have significantly decreased QOL and exposure to risk. Shared decision making, is believed to diffuse decisional distress accompanying complex situations. Methods: Semi-structured interviews explored patient, caregiver and physician perceptions of standard of care treatment recommendations following diagnosis. Cognitive, neurological and functional ability was evaluated with neurological examination, Karnofsky Performance Scale (KPS), Trail-Making Test and The Hopkins Verbal Learning Test (HVLT). Physical and emotional distress was scored with the FACT-BR and the MD Anderson Symptom Inventory (MDASI). Results: Common themes emerging from patients’ interviews were identified, characterized and evaluated in comparison to those of treating physicians and caregivers. Several themes pertained to existential concerns, all of which were underappreciated by the physicians and to a lesser extent caregivers. Physicians emphasized the potential advantages of improved survival within a limited lifespan, but this advantage was perceived by patients as a binary life or death construct without differentiation of prognostic subtleties. Physicians and caregivers perceived shared decision making to be occurring to a greater degree than did patients. Cognitive and language dysfunction were not significant barriers to communication in this group of patients. Conclusions: Although physicians believed that shared decision making was occurring, there was poor patient comprehension of the complex situation and patients did not feel empowered or capable to make independent decisions. Patients endorsed moderate to severe distress in the setting of these treatment decisions. Improved physician-patient communication and patient education is needed to support engagement of patients and caregivers in therapy, to address the overwhelming existential crisis that patients face, and to avoid shepherding patients into treatments that are poorly understood, insufficiently explained for informed consent purposes, or accompanied by unrealistic expectations.
Making treatment decisions at end of life in a comprehensive cancer center.
Authors: Beck Anna Catherine , Ellington Lee , Mooney Kathi
Published: February 2017

51

Background: End of life treatment decisions are challenging for cancer patients and oncology providers. Patients must understand their prognosis and options, deciding if and when to increase palliative care and decrease tumor-focused therapy. Cancer centers committed to offering clinical trials and evaluate new therapies add complexity to these decisions. To better define crucial points for decision making, we reviewed the care patients received during the last 6 months of life at one comprehensive cancer center. Methods: A retrospective chart review was conducted of the 301 cancer patients who died during one calendar year and were treated at the Huntsman Cancer Institute. We abstracted the care documented from all clinic visits, phone calls and hospitalizations including referrals and resources utilized during the last 6 months of life. Results: Men and women were equally represented with a mean age of 61at death and a median survival of 13 months after diagnosis. Over 1780 outpatient visits were documented during the last 6 months of life with treatment decision conversations noted at 68% of visits. Results of these discussions included new chemotherapy initiated at 26% of visits, treatment termination at 19% of visits, palliative therapy only at 9% of visits, and no treatment change at 47% of visits. Of the 64% of patients receiving chemotherapy in the last 6 months, 32% continued therapy in the last 30 days of life. Similarly, 34% of patients received radiation therapy in the last 30 days. Hospice was used by 59% of patients, with a mean length from referral to death of 29 days. Conversations about hospice occurred in 65% of patients with a mean/median of 2 conversations/patient. Approximately 37% of these conversations resulted in hospice enrollment, 49% deferred a decision and in 14% the patient requested additional treatment. Conclusions: Defining optimal timing for stopping cancer directed therapy is challenging in medical and radiation oncology, with 1in 3 patients continuing treatment in the last month of life. Goals of care and hospice conversations were required on multiple occasions, underscoring the need for oncology providers to have highly honed communication skills to minimize futile care and maximize palliative care.
Experience with palliative sedation (PS) in an inpatient oncology setting.
Authors: Prado Bernard Lobato , Gomes Diogo Bugano Diniz , Uson Junior Pedro Luiz Serrano , Taranto Patricia , Franca Monique Sedlmaier , Eiger Daniel , Mariano Rodrigo COUTINHO , Hui David , Del Giglio Auro
Published: February 2017

63

Background: Palliative sedation (PS) is an intervention to treat refractory symptoms and to relieve suffering at the end of life. Its prevalence and practice patterns vary widely. Methods: This is a retrospective study of the use of PS in cancer patients who died at our comprehensive cancer center between March 1, 2012 and December 31, 2014. PS was defined as the use of continuous infusion of midazolam or neuroleptics for refractory symptoms as stated in the progress notes. Patients who died in the ICU were excluded. The aim of our study was to evaluate PS practice patterns, describing its frequency, clinical indications and outcomes. Results: During the study period, 556 cancer patients died at the institution and 203 (36.5%) received PS. Main reasons for exclusion were death in the ICU (168 patients) and no use of midazolam or neuroleptics (77 patients). Patients who received PS as compared to those not sedated were younger (67.8 vs. 71.5 years-old, p = 0.007) and more likely to have a primary diagnosis of lung cancer (23% vs. 15% p < 0.001). Patients receiving PS were more likely to be seen by oncology/hematology rather than other specialties (70% vs 45% p < 0.001) and more likely to have a longer hospital stay from admission to death (47.9 days vs 26.2 days p < 0.001). Only 25 patients (12%) were seen by a dedicated palliative care team. The most common indications for sedation were dyspnea (51.5%) and delirium (19.5%) and the most common dugs used were midazolam (52.9%) or midazolam and a neuroleptic (39.2%). Median initial midazolam infusion rate was 0.75 mg/h (interquartile range – IQR - 0.6-1.5) and final rate was 1.5 mg/h (IQR 0.9-3.0). Median time from sedation to death was 27 hours (IQR 12-58). Conclusions: Palliative sedation is a common practice at our hospital and it is not associated with shortening of hospital stay. Further research is needed to identify factors that may affect the frequency and outcomes associated with palliative sedation.
Patient reported outcomes (PROs) in patients with human papilloma virus (HPV) positive versus negative head and neck cancer (HNC).
Authors: Bauman Jessica Ruth , El-Jawahri Areej , Quinn Karen , Arcikowski Lisa , Chan Gina , Viscosi Elene , Doherty Carol , Clark John Ross , Wirth Lori J. , Temel Jennifer S.
Published: February 2017

87

Background: HNC caused by HPV has become an epidemic. Treatment for HNC results in a tremendous symptom burden. The impact of HPV-status on quality of life (QOL) and how this effects illness perception and mood has not been described. We sought to explore differences in PROs in patients with HPV + vs. - HNC. Methods: This is a secondary analysis of data from a prospective, longitudinal intervention study of 60 patients with newly diagnosed HNC undergoing concurrent chemoradiation. 30 control patients received standard care followed by 30 intervention patients who received an educational intervention. Satisfaction (information satisfaction questionnaire (ISQ)), mood (Hospital Anxiety and Depression Scale (HADS)), illness perception (Brief Illness Perception Questionnaire (IPQ)), and QOL (MD Anderson Symptom Inventory- Head and Neck (MDASI-HN)) were evaluated at baseline and 3 weeks. Data were analyzed using linear regression models controlling for the effect of the intervention to assess the association between HPV status and changes in PROs. Results: From 8/2014 to 10/2015, we enrolled 60 patients (2 excluded for hospitalization or care elsewhere). 29/58 (50%) had HPV + HNC. 40 (69%) were men. 54 (93%) had stage III/IV disease. Compared to patients with HPV - HNC, patients with HPV + HNC reported an increase in symptom burden, symptom interference, and depressive symptoms, as well as a more threatening illness perception from baseline to 3 weeks. There were no differences in anxiety or satisfaction. Table 1 details the regression models. Conclusions: Patients with HPV + HNC have a larger decrement in QOL during treatment than patients with HPV - HNC, which corresponds to a more threatening illness perception and more depressive symptoms. Interventions tailored to symptom management and mood should be developed for this unique population. [Table: see text]
Oncologists' dispositional affect and likelihood of end-of-life discussions.
Authors: Pirl William F. , Lerner Jennifer , Traeger Lara , Greer Joseph A. , El-Jawahri Areej , Temel Jennifer S.
Published: February 2017

9

Background: Oncologist-patient end-of-life (EOL) discussions are associated with less aggressive care at EOL. Prior research on EOL discussions has not explored the role of oncologists’ dispositional affect, trait patterns of emotional responses. Affect could possibly facilitate or hinder broaching difficult EOL topics. We examined associations between oncologists’ disposition for experiencing positive and negative affect and likelihood of EOL discussions reported by their patients with advanced cancers. Methods: 350 patients with incurable lung and GI cancers were enrolled in a randomized trial of early palliative care within 8 weeks of diagnosis. Oncologists providing care for participants completed a measure of dispositional affect, Positive and Negative Affect Schedule (PANAS). Positive and negative affect scales were analyzed dichotomously (above/below sample median). At 24 weeks in the trial, patients reported if they had ever discussed with their oncologist the care they would want to receive if they were dying (yes/no). Associations between oncologists’ affect and patient-reported EOL discussions were tested with multilevel models clustered by oncologist, adjusting for patient age, cancer type, and randomization. Results: At 24 weeks, 57/242 (23.6%) patients reported having had EOL discussions. The PANAS was completed by 17/19 (89%) oncologists with patients in the trial. Patients treated by oncologists with higher negative affect reported more EOL conversations, but this did not reach statistical significance: OR = 1.76 [.81, 3.83], p = .15. Patients treated by oncologists with higher positive affect also reported more EOL conversations, but this did not reach statistical significance: OR = 1.66 [.83, 3.35], p = .15. However, patients treated by oncologists with both higher positive and higher negative affect were over 3 times as likely to report having had EOL discussions: OR = 3.22 [1.02, 10.23], p = .046. Conclusions: Patients treated by oncologists with greater propensity to experience both positive and negative affect were more likely to report EOL discussions compared to those treated by oncologists who experience lower levels of affect. More research is needed to better understand these relationships.
Factors associated with quality of life in a cohort of patients with palliative advanced cancer from a developing country: Relevance of perception of cancer curability.
Authors: Perez-Cruz Pedro Emilio , Langer Paola , Carrasco Escarate Cecilia , Bonati Pilar , Batic Bogomila , Tupper Satt Laura , Gonzalez Otaiza Marcela
Published: February 2017

93

Background: Improving quality of life (QOL) is a key goal in palliative care for patients with advanced cancer. Most studies about QOL in palliative care patients have been performed in the developed world. However, little is known about the factors that influence patients QOL in developing countries. The aim of this study is to describe factors associated with QOL in a cohort of patients with advanced cancer who were enrolled in the outpatient clinic public hospital in Santiago, Chile. Methods: Patients with advanced cancer admitted to the National Program of Palliative Care at a public Hospital in Santiago, Chile were prospectively enrolled in a study to assess QOL longitudinally. QOL was assessed with the EORTC-QLQ-PAL 15 questionnaire. Demographics, symptom intensity, depression and anxiety were assessed. Descriptive statistics and regression analysis were performed. Information about cancer curability and perception of personal health were also included. Results: In this preliminary report, the first 37 patients were included. Baseline characteristics were: mean patient age was 64, 21 (57%) females, 14 (38%) had GI cancer, 7 (19%) lung cancer, 4 (11%) breast cancer and 12 (22%) other. Mean (SD) QOL was 63 (34) in a 0 to 100 scale. QOL was not associated with age, gender, functionality, depression, anxiety, spiritual pain or financial distress. QOL was negatively associated with total symptom burden (coef -.53, p = .48), and positively associated with believing that cancer was curable (coef 33.3, p = .003). In a multivariate analysis, QOL was independently associated with both lower overall symptom burden (coef -.55, p = .38) and believing that cancer was curable (coef 28.6, p = .009). Conclusions: In palliative care patients with advanced cancer from a developing country, QOL was associated with lower overall symptom burden and with believing that cancer was curable. Further studies are needed to explore whether clarifying prognostic information about cancer curability in developing countries may impact patients’ QOL.
Post-prostatectomy salvage radiation therapy in prostate cancer upon identification of biochemical failure.
Authors: Peddada Suneal Gopal , Oliver Craig , Phelps Angela , Stokes Steven H. , Adkison Jarrod Bartlett
Published: February 2017

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Background: Prostate Specific Antigen (PSA) values post-prostatectomy are used as an indication for salvage radiation therapy. It has been suggested that initiation of therapy at lower PSA values lead to better outcomes. This study investigates outcomes of salvage radiation therapy at specific PSA thresholds. Methods: One hundred two prostate cancer patients were treated with salvage radiotherapy at our institution with curative intent, 19 of whom had Gleason score ≤6, 52 of whom had Gleason 7, and 31 with Gleason ≥8. Median follow-up after radiotherapy was 51 months. The median PSA prior to salvage radiotherapy was 0.33 ng/mL, and the median time from prostatectomy to radiotherapy was 24.6 months. Positive margins were identified in 52 patients, and perineural invasion was positive in 83. The median dose delivered was 64.8 Gy. Results: The 5-year actuarial freedom from biochemical failure rates for NCCN low, intermediate, and high risk groups were 100%, 77%, and 62%, p=0.2449. The 5-year actuarial freedom from biochemical failure rates for Gleason score ≤6, Gleason 7, and Gleason ≥8 patients were 87%, 72%, and 49%, p=0.0187. Patients with pre-radiotherapy PSA ≤0.5 ng/mL had better 5-year biochemical control relative to patients with higher pre-radiotherapy PSA, 76% versus 51%, p=0.0211. The pathological margin status did not predict for biochemical control after salvage radiation across the different Gleason grades. Very few interval biochemical failures are observed after the 5-year point of follow-up. The 5-year overall survival for the entire cohort is 92%, with prostate cancer specific survival of 96%. Conclusions: Salvage radiotherapy demonstrated favorable efficacy with durable PSA control and few failures 5 years post radiation. Initiation of salvage radiotherapy for PSA ≤0.5 ng/mL demonstrated improved biochemical control, supporting the adoption of early referral to radiation oncology once post-prostatectomy biochemical failure is identified. [Table: see text]
Risk factors for significant prostate cancer in radical cystoprostatectomy specimen: A retrospective analysis.
Authors: Thissen Andrea Katharina , Porres Daniel , Pfister David J. K. P. , Heidenreich Axel
Published: February 2017

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Background: Prostate cancer (Pca) has been found incidentally in radical cystoprostatectomy (RCP) specimens in 27-70%. We evaluated histopathological features and clinical outcome of patients with incidental Pca undergoing RCP for urothelial bladder cancer and identified potential risk factors for the presence of significant Pca, being defined as Gleason Score ≥7b, primary tumor ≥T2c or Pca volume ≥0.5cm3. Methods: A retrospective analysis of patients who underwent RCP between 01/2005-03/2015 was performed with regard to clinical data and pathohistological features. Whole mount serial sections of specimens were examined in the same urological and pathological institution. Pca grade, p-stage, cancer volume and surgical margins were recorded. Preoperative PSA values and follow-up were analysed. Results: We identified 71 patients with incidental Pca with a mean age of 71.7 years (47-84 years). 33/71 patients (46.5%) had significant Pca (28.2% ≥T2c, 4.2% GS ≥7b [+≥T2c], 14.1% cancer volume ≥0.5cm3[+≥T2c]). Other features were as follows: pT2a, n=36 (50.7%); pT2b, n=2 (2.8%); GS 6, n=50 (70.4%); GS 7a, n=18 (25,3%). All patients were R0 and N0 for Pca. Mean preoperative PSA level was 2.7ng/ml. None of the patients developed biochemical recurrence (median follow-up: 29.5 [1-124 months]). Patients with significant Pca were older than those with insignificant Pca (median age 71.2 years vs 70.1 years) and had higher preoperative PSA levels: 90% of patients with a PSA level of 4-10ng/ml had a ≥T2c Pca, while 81.5% of patients with PSA levels of 0-1ng/ml had a pT2a Pca. P-stages in patients with PSA values between 1-4ng/ml were found to be equally distributed between pT2a-pT2c. Conclusions: The occurence of incidental Pca is a common finding in patients undergoing RCP, with a considerable proportion having the characteristics of significant Pca. Potential risk factors for significant Pca are older age and PSA levels >4ng/ml. However, none of the patients experienced biochemical relapse or Pca-related death during the follow-up. In line with published data, incidental Pca does not impact on the oncological outcome of patients undergoing RCP. The prognosis is primarily determined by bladder cancer.
Active surveillance: How to measure, manage, and improve.
Authors: Gaylis Franklin , Cohen Edward , Calabrese Renee , Prime Hillary , Dato Paul , Kane Christopher J.
Published: February 2017

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Background: Active surveillance (AS) is an important strategy to limit the overtreatment of low risk prostate cancer (PCa). A best practice was established for AS inclusion criteria and follow-up, aimed to measure past AS adoption rates, institute the best practice, then measure AS adoption. Methods: Patient biopsy and treatment data was retrieved from an integrated EMR (Allscripts). AS adoption rates were calculated using 4 methods: 1) All newly diagnosed PCa patients; 2) Newly diagnosed PCa patients treated at Genesis Healthcare Partners (GHP); 3) Patients eligible for AS treatment according to the National Comprehensive Cancer Network (NCCN) (very low risk and low risk categories) guidelines and treated at GHP; and 4) Patients eligible for AS treatment according to the UCSD/GHP best practice and treated at GHP, according to the following inclusion criteria: Stage T1c; PSA Density (PSAD) < 0.15 ng/mL/cc and absolute PSA level < 10 ng/mL; Gleason ≤6; ≤3 cores (+); No individual core with >50% involvement. Between 2013 and 2014, GHP physicians underwent an educational training program on the UCSD/GHP best practice. Comparative report cards on AS adoption were sent to all physicians. Results: See Table. Conclusions: AS adoption improved in those patients considered most eligible (according to evidence based guidelines) for AS following institution of an educational program and comparative reporting in a community practice. Selection criteria appear to significantly impact AS adoption rates. [Table: see text]
Does variation in prostate volume calculated with MRI versus TRUS lead to reclassification of men based on current PSA density threshold for active surveillance criteria? Result from a prospective cohort.
Authors: Rai Samarpit , Patel Amil , Pavan Nicola , Soodana-Prakash Nachiketh , Balise Raymond R , Nahar Bruno , Satyanarayana Ramgopal , Parekh Dipen , Punnen Sanoj
Published: February 2017

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Background: PSA density (PSAD) is a strong predictor of aggressive prostate cancer (PCa) and is often used as a selection criterion for active surveillance. However, measurement of PSAD can vary depending on the modality used to estimate prostate volume (PV). We analyzed a prospective cohort of men undergoing MRI−US fusion biopsy to assess the variation in PV obtained with both imaging modalities, and investigate the impact of this variation on PSAD measurement in order to determine if it led to re-classification of patients above or below the current threshold of PSAD used in clinical practice (0.15 ng/mL/cc). Methods: All men were consecutively enrolled in this prospective study and had their PV measured on MRI prior to prostate biopsy (PB), and on Trans-Rectal Ultrasound (TRUS) at the time of PB. PSAD was calculated by dividing the last PSA prior to biopsy by the PV ascertained with each imaging modality. We used paired t-tests and Wilcoxon signed−rank tests to compare the difference in PV and PSAD obtained with TRUS and MRI. We also categorized PSAD measurements on each imaging modality above and below a cut-off of 0.15 ng/mL/cc. We used the McNemar’s test for paired proportions to estimate the significance of discordance in PSAD categorization based on each imaging modality. Results: Of the 124 men, the mean PV assessed with MRI (70 cc) was 7 cc more on average (SD: 11, median = 4 cc) than that obtained with TRUS (63 cc) (P < 0.0001). Furthermore, the mean PSAD obtained with MRI (0.17 ng/mL/cc), was 0.01 ng/mL/cc lower (SD: 0.07, median = 0.01) than that obtained with TRUS (0.18 ng/mL/cc) (P < 0.0001). 118 (95%) men had concordant PSAD values assessed with either imaging modality using the cut-off of 0.15 ng/mL/cc. All 6 (5%) men with discordant PSAD values who were above the cut-off with PV obtained via TRUS were reclassified as being below the cut-off with PV assessed via MRI (P < 0.01). Conclusions: MRI can overestimate PV compared to TRUS. This may translate to reclassification of men around the currently used PSAD threshold and have implications for treatment decision making and selection of patients for active surveillance.
Gene expression profiling of prostate tissue based on variable expression of 5-alpha reductase 2.
Authors: Salari Keyan , Bechis Seth , Ge Rongbin , Hong Jian , Otsetov Aleksander , Wang Zongwei , Wu Chin-Lee , Tabatabaei Shahin , Olumi Aria F.
Published: February 2017

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Background: Androgen signaling plays a central role in the pathophysiology of both benign and malignant prostatic disease. We previously showed that some men carry epigenetic modifications of the 5-alpha reductase (AR) promoter that modulate gene expression, raising the hypothesis that there may be molecular heterogeneity underlying the variability in clinical response to 5-AR inhibitors for management of benign and malignant prostatic diseases. In this study, we performed whole-genome expression profiling of prostatic tissue based on variable expression of 5-AR2 to determine whether molecular subtypes of clinical relevance could be identified. Methods: Prostatic tissue specimens were obtained from 22 patients with symptomatic BPH undergoing prostate debulking surgery. 5-AR2 protein expression was measured by immunohistochemistry, and 5-AR2 promoter methylation determined by PCR. RNA was extracted from each specimen and whole-genome expression profiling was performed using Illumina Human BeadChip Arrays. Gene expression data was analyzed by unsupervised hierarchical clustering and Gene Set Enrichment Analysis. Results: Unsupervised hierarchical clustering identified two subtypes of patients with distinct gene expression signatures. Among the most differentially expressed genes were several notable androgen-regulated genes, including TMPRSS2, NKX3-1, AZGP1, KLK3 (encoding the PSA protein) and multiple other members of the kallikrein family of serine proteases (all P< 0.001, FDR < 0.02). Multiple gene sets composed of androgen-regulated genes and androgen receptor target genes were found to be significantly enriched in one of the two subtypes. Interestingly, patients from this Androgen-Up subtype were also noted to have a higher frequency of 5-AR2 promoter methylation (though not statistically significant). Conclusions: Our findings suggest that there are distinct molecular subtypes among prostatic tissues with variable expression of 5-AR2, driven by differences in androgen gene regulation. These differences may partially explain the variable response to 5-AR inhibitors and thereby inform clinical strategies for devising therapies for benign and malignant prostatic disease.