bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective routine electronic symptom screening and use of evidence to improve cancer symptom management in Ontario, Canada.
Authors: Molloy Sean , Green Esther , Pereira Jose , Tabing Reena , Sawka Carol Anne
Published: March 2020

e20507

Background: Improving symptom management is a critical component of high quality care. Cancer Care Ontario (CCO) is working to improve through a standardized approach to symptom screening and assessment that leverages electronic tools along the cancer journey. Methods: CCO has developed a web-based application that allows patients to report their symptoms using the Edmonton Symptom Assessment System (ESAS). ESAS is a validated screening tool that asks patients to rate the severity of nine common cancer symptoms. The use of ESAS promotes a common language among patients and providers and across care settings. To support clinicians in determining follow-up to scores, CCO has developed symptom management guides. The guides represent current evidence and best practices and are available in various formats to help the care team assess and manage a patient’s cancer-related symptoms. Results: Since the program’s introduction in 2007, over 1.6 million ESAS screens have been performed across the province. In November 2012, over 53% of all Regional Cancer Centre patients were screened representing over 23,000 patients and nearly 35,000 ESAS screens. Symptom assessments collected from 45,000 cancer patients revealed that 75% of patients reported fatigue as a concern, 57% reported anxiety and 53% reported pain. Patients have indicated that they value this approach. Results from a 2012 survey of 3,320 patients show that 93% thought that indicating their symptom severity is important as it helps their health care providers know how they are feeling. Evidence from chart audit reviews demonstrates that symptom screening is linked to higher rates of documented clinical interventions but further research is needed to analyze its impact on outcomes. Conclusions: Lessons learned include the importance of leadership at all levels, clinician engagement in change, point of care decision support tools and the importance of engaging patients in the management of their symptoms. Patients are overwhelmingly in support of this approach to cancer symptom screening and their involvement is critical to its expansion across all settings of care.
Epoetin biosimilars in the management of chemotherapy-induced anemia in elderly patients: A subanalysis of the ORHEO study.
Authors: Kurtz Jean-Emmanuel , Soubeyran Pierre-Louis , Michallet Mauricette , Luporsi-Gely Elisabeth
Published: March 2020

e20513

Background: Chemotherapy-induced anemia (CIA) treatment requires transfusion, or epoietin administration. Elderly patients (pts) may experience severe complications from CIA, with fatigue and cardiovascular events. Methods: ORHEO (place of biOsimilaRs in the therapeutic management of anemia secondary to chemotherapy in HaEmatology and Oncology) was a post-marketing, observational, prospective, multicentric study. Adult CIA (Hb<110g/l) pts with solid tumors, lymphomas or myelomas and eligible for epoetin alpha biosimilar (EAB) treatment were included to receive EAB according to drugs approval recommendations. Recorded data included demographics, performance status, blood count and iron load profile. Safety (NCI-CTC V2.0) and efficacy were also assessed. The primary study endpoint was the rate of responders (defined as increase in Hb levels to 100 g/l or at least 10 g/l since inclusion visit, or reaching target Hb set at start of study, without any blood transfusions in the 3 weeks prior to measurement) at +3 months (M+3). Other endpoints included safety, patterns of treatment interruption and rate of responders at +6 months (M+6). Here we present data for the elderly (>= 70 years old) pts. Results: 1,009 pts (54.3% male, 45.7% female) >= 70 y.o. were included in this analysis. Median age was 77 y, range [70-93]. At baseline, 36.3, 57.8 and 3.4% of pts had respectively grade 1, 2 and 3 anemia. Iron supplementation was given in 9.9 (oral) and 16.0% (IV) of pts. At M+3, 84.0% of pts were responders (IC95% 81.4-86.3). Moreover, respectively 241 pts (23.8%) and 139 pts (13.7%) had stopped EAB permanently or temporarily, mainly because of efficacy (45.2 and 79.1% respectively); other reasons were side-effects (2.9 and 0.7% respectively), lack of efficacy (7.0 and 4.3%), and unspecified reason (44.8 and 15.8%). Similar results were observed at M+6 with 86.8% of responders. 17.0% of pts reported side effects (all grades); the most frequent were thromboembolic events (4.5%). No EAB-related death was reported. 94.6% of pts reported being satisfied with EAB therapy at M+3 and M+6 and willing to restart if needed. Conclusions: EAB therapy is efficacious on CIA management in elderly pts with low toxicity.
Robustness of circadian rest-activity rhythm for predicting efficacy of intravenous cetuximab (Cet) and hepatic artery infusion (HAI) of chronomodulated irinotecan, 5-fluorouracil and oxaliplatin (Chrono-Optiliv) for liver metastases from colorectal cancer (LM-CRC) (Optiliv translational study, NCT00852228).
Authors: Karaboué Abdoulaye , Innominato Pasquale F. , Bouchahda Mohamed , Mocquery Magali , Bossevot Rachel , Plessis Virginie , Bouchoucha Davina , Adam Rene , Levi Francis ,   ARTBC International Chronotherapy Group
Published: March 2020

e20519

Background: The rest-activity rhythm is a biomarker of the circadian timing system, whose disruption both accelerates cancer progression in experimental models (Filipski et al. JNCI 2002, 2005) and predicts for poor overall survival in cancer patients (pts) (Innominato et al. Cancer Res 2009; Int J Cancer 2012). Here we investigate the relevance of early signals of circadian disruption for the antitumor efficacy of intravenous Cet and chronomodulated triplet HAI in pts with unresectable and refractory LM-CRC. Methods: Rest-activity was monitored q1min using a wrist watch actigraph worn for three weeks, starting 1 week before HAI onset. A robust and validated parameter (I<O), the relative measure of activity In-bed vs Out-of-bed, was used to evaluate rest-activity patterns. Tumor response was evaluated using RECIST criteria. Results: 10M and 3F, aged 33-72 y (median, 60 y) had a good Performance Status (0, 10 pts; 1, 3 pts) and received one (7 pts), two or three (6 pts) prior chemotherapy lines. Pts displayed complete or partial response (1 CR, 6 PR), or stable disease (SD, 6 pts). Median I<0 was 95.4% (25-75% quartiles, 88.8-98.0) at baseline, 92.8% (89.4- 96.2) during the treatment week (p<0.001 vs “baseline”) and 95.0% (89.2- 97.6, NS) on the week after HAI. On this last week, I<O improved or recovered fully in 5 pts (38.5%), or partly in 3 pts (23.1%). Rest-activity rhythm disruption persisted in 5 pts (38.5%). An objective tumor response was achieved in 7/ 8 pts whose I<O improved or recovered (87.5%) while the poor I<O computed for 5 patients on the week after HAI predicted for SD only (p=0.003). This relation was independent of PS and prior chemotherapy lines (p=0.013). Conclusions: The robustness of the rest-activity rhythm during the first course of Chrono-Optiliv was an early signal that predicted subsequent antitumor activity. Further testing of this circadian biomarker is warranted as an early surrogate endpoint of antitumor efficacy of Chrono-Optiliv. Clinical trial information: NCT00852228.
Leucovorin (LV) pharmacokinetics in patients receiving high dose methotrexate (HDMTX), with or without glucarpidase treatment.
Authors: Schwartz Stefan , King Thomas , Ward Suzanne , Ogden Angela , Chauhan Nikhil , Howard Scott C.
Published: March 2020

e20521

Background: Glucarpidase is a recombinant form of carboxypeptidase G2 and hydrolyzes MTX into inactive metabolites and provides alternate clearance in pts with delayed elimination and acute kidney injury. It is administered with IV hydration, urinary alkalinization, and LV. The primary objective was to investigate whether glucarpidase reduces exposure to LV and its active metabolite (5EMeTHF) to below the level achieved in pts who have not received glucarpidase, by assessing the PK of the active L-isomer of LV (6S-LV) following administration of HDMTX and LV. Methods: Open-label, multicenter PK study in pts treated with HDMTX (≥1 g/m2) and LV (either ≥15 mg or ≥10 mg/m2) with subsequent glucarpidase where indicated for renal impairment (Arm A) or without glucarpidase (Arm B). Plasma samples for LV and 5EMeTHF were taken pre-LV and at 5, 30, 60, 120, and 180 min after LV to calculate the area under the concentration curve of 6S-LV over 0-3 hours (AUC0-3) following the LV dose. Results: 17 pts (8 Arm A, 9 Arm B) were analyzed. The median pre-glucarpidase methotrexate (MTX) plasma concentration was higher for Arm A 7.5 µmol/L) than B (1.1 µmol/L). Similarly, median LV doses were 89.88 mg/m2 (Arm A) and 13.51 mg/m2(Arm B). Mean 6S-LV AUC0-3 values (µmol*h/L) for Arm A were 8.70±5.56, compared with 1.31±0.78 for Arm B, consistent with Arm A receiving a higher LV dose than Arm B. Mean 6S-5MeTHF AUC0-3 values (µmol*h/L) were similar in arms A and B (0.68 and 0.73). When normalized for LV doses, mean 6S-LV AUC0-3values (µmol*h/L) were similar between arms:10.02±4.83 in Arm A versus 9.79±5.18 for Arm B. Conclusions: Glucarpidase does not reduce exposure to 6S-LV and 5-MeTHF to below the level achieved in patients with normal renal function who did not receive glucarpidase. Adequate LV exposure is achieved if LV dosing is based on pre-glucarpidase plasma MTX concentration for at least 48 hours after glucarpidase administration. Clinical trial information: NCT00634504.
Rapid assessment of frailty prior to treatment of elderly colorectal cancer patients.
Authors: Dhesy-Thind Sukhbinder K. , Meyers Brandon Matthew , Al-Shamsi Humaid Obaid , Papaioannou Alexandra , Zbuk Kevin M. , Pond Gregory Russell
Published: March 2020

e20522

Background: Frailty is traditionally assessed by a comprehensive geriatric assessment (CGA); there is no agreed upon standard for a CGA, and it is not feasible to implement in routine oncology practice. In contrast, the Edmonton Frailty Scale (EFS) is a simple questionnaire, requiring less than 5 minutes to complete, initially validated as a surrogate to the CGA in general medicine patients (Rolfson et al, 2006). We conducted a pilot study to establish if the EFS would add utility beyond clinician’s expertise. Methods: The EFS was administered to stage II-IV CRC patients ≥70 years, referred to a Medical Oncologist at a tertiary care centre. The EFS was completed by one of the investigators, with the treating oncology team blinded to results, and follow up of 14 months. Results: Forty-six patients were enrolled with the following characteristics: average age 76, 48% male, and 78% Zubrod performance status (PS) 0-1. The EFS was reproducible between visits (r = 0.81 [95%CI 0.64-0.9], p<0.01). No association existed for the EFS and receipt of chemotherapy for the study population as a whole, however none of the stage II patients had features requiring chemotherapy. Restricting the analysis to stage III/IV patients demonstrated a reduced likelihood of receiving chemotherapy with higher EFS scores (Odds ratio 0.56 per unit increment [95%CI 0.37-0.85] p<0.01). A similar effect was observed after multivariate analysis (adjusting for PS, age, stage and gender, Odds ratio 0.41 per unit increment [95%CI 0.18-0.96] p<0.05). The clinician’s qualitative impression was associated with the EFS (p<0.01). No association existed between the EFS and upfront dose reductions, choice of less toxic regimens, or hospitalization secondary to grade 3/4 toxicities. Conclusions: The EFS can identify patients that Oncologists may have thought were too frail for chemotherapy, independent of PS. The EFS has the potential to add a reproducible, and quantifiable measure of frailty to aid in decision making in oncology practice.
Second primary malignancies in acute myeloid leukemia.
Authors: Nepal Barsha , Ghimire Krishna Bilas , Shah Binay Kumar
Published: March 2020

e20529

Background: Long-term survival rate in acute myeloid leukemia (AML) patients younger than 60 yrs is higher than 40% (Mayer RJ, et al N Engl J Med 2004). Development of second primary malignancy (SPM) in these patients is unknown. We analyzed the incidence of SPM in these AML patients using SEER database. Methods: We analyzed the Surveillance, Epidemiology, and End Results (SEER*Stat) database: Incidence - SEER 13 Regs Research Data, Nov 2011 Sub, Vintage 2009 Pops (1992-2009) using multiple primary standardized incidence ratio (MP-SIR) session. We evaluated SPM incidence rate among adult AML patients (age 20-59 yrs) during the period 1992 - 2009. We used SEER*Stat software for statistical analysis. Results: Total number of AML patients (age 20-59 yrs) reported during 1992-2009 period was 5,544. Median age at the time of diagnosis of SPM was 54.33 yrs ( 22.33-72.42 yrs). Median follow up was 8.13 yrs (2months – 17.8 yrs) and median latency period was 51 months ( 2-193months). The total number of all site SPM among AML patients reported during same time period was 100 with observed/expected (O/E) ratio of 1.03, (95% CI: 0.84-1.26), excess risk of 1.62 per 10,000 population. Ninety patients with AML developed SPM; 86 AML patients developed only 1 SPM and 7 patients developed 2 SPMs. The risk of oral cavity and pharyngeal cancer was significantly increased in AML patients with O/E: 3.99, p<0.05 (95% CI: 1.99-7.15), excess risk of 3.98 per 10,000 population. Similarly, cancer of urinary system was significantly increased in AML patients with O/E: 2.26, p<0.05 (95% CI: 1.23-3.79), excess risk of 3.77 per 10,000 population. Conclusions: This study showed significantly higher risk of second primary malignancies of oral cavity/pharyngeal cancer, and of urinary system in AML patients. [Table: see text]
Efficacy of a one-year exercise program to prevent bone loss in postmenopausal women prescribed aromatase inhibitor therapy: An RCT.
Authors: Kilbreath Sharon , Refshauge Kathryn M. , Beith Jane McNeil , Ward Leigh C. , Clifton-Bligh Philip , Simpson Judy M. , Moore Katrina H. , Lee Mi-Joung , Nery Lisa
Published: March 2020

e20533

Background: The aim of this single blinded RCT was to determine the effect of exercise on bone mineral density (BMD) in postmenopausal women prescribed an aromatase inhibitor (AI) for the treatment of breast cancer. Methods: 66 sedentary, postmenopausal women, median age of 54.5 years, with early breast cancer and receiving an aromatase inhibitor participated. Women were stratified for taking tamoxifen prior to AI, and randomised to either the exercise (n = 27) or control (n = 39) group. All participants received daily vitamin D (1000 IU) and calcium carbonate (1200 mg) supplements and a booklet from Osteoporosis Australia outlining the benefits of exercise in preventing osteoporosis. The exercise group attended a gym three times per week for one year, supervised at regular intervals by a personal trainer, and were contacted weekly regarding progress and progression. Training sessions comprised warm-up, impact training, and resistance training. The control group was contacted monthly to monitor health status and to receive their supply of vitamins. The primary outcome was total hip BMD measured with a dual-energy X-ray absorptiometer. The secondary outcomes included trochanteric, femoral neck, lumbar spine and whole body BMD and t-scores. Results: Intention-to-treat analysis revealed that the change in BMD was not significantly different between groups. At baseline, the mean (SD) total hip BMD in the control group was 0.892 (0.115) g/cm2 and 0.878 (0.112) g/cm2 at 1 yr. In contrast, hip BMD in the Exercise group was 0.918 (0.119) g/cm2 at baseline and 0.910 (0.113) g/cm2at 1 yr. The mean (SD) change for both groups was <1%. The mean T-score of the hip for Controls at baseline was -0.42 (0.94) and -0.53 (0.91) at 1 year. The baseline T-score for the Exercise group was -0.20 (0.95) and -0.26 (0.93) at one year. The average compliance with attendance for the exercise group was 71% but ranged from 20 to 100%. Compliance with vitamins for both groups was high. Conclusions: A one year exercise program did not provide additional benefit to bone density in women on AIs compared to receipt of calcium and vitamin D and advice to exercise. Clinical trial information: (ACTRN12608000220369).
The incidence and impact of poor nutrition in gastrointestinal malignancies.
Authors: Guggenheim Douglas Eric , Ocean Allyson J. , Popa Elizabeta C. , Magli Amanda R , Karpenko Irene , Christos Paul J. , Rosales Veronica A. , Florendo Erika Ocampo , Ruggiero Joseph T. , Shah Manish A.
Published: March 2020

e20549

Background: The impact and significance of malnutrition in gastrointestinal oncology is understudied. The Subjective Global Assessment (SGA) is a validated clinical tool to assess nutritional status. We examined baseline SGA to determine its significance across GI malignancies. Our hypothesis is that malnutrition is prevalent in gastrointestinal malignancies and may significantly affect treatment-related morbidity. Methods: The Weill Cornell Medical Center GI registry is a prospective database to collect clinical standardized data from all patients who present for evaluation in the outpatient academic practice office. We examined baseline SGA score (A=well nourished, B=moderate malnutrition, C=severe malnutrition) in all patients newly diagnosed with a GI malignancy, and correlated with baseline patient demographics, tumor type, and dose reductions in the first 2 months of chemotherapy treatment by the chi-square test and t-test. Results: From May-Dec 2012, 101 newly diagnosed GI cancer patients referred to oncology were enrolled. 23% of patients were SGA-B/C, and significantly associated with race and albumin. Among upper GI patients with poor nutrition, 75.0% required dose reductions within the first 2 months of treatment, resulting in a mean percent dose received of 78.3 ± 19.1. Conclusions: Moderate to poor nutrition is prevalent in ~23% of patients with GI malignancies, and significantly more prevalent in upper GI and pancreatobililary cancers. Moderate malnutrition is associated with low albumin, and for upper GI patients, reduced chemotherapy delivery, suggestive of increased toxicity. [Table: see text]
Plasma vascular endothelial growth factor level and cognitive changes in breast cancer patients.
Authors: Ng Terence , Cheung Yin Ting , Ham Guo Maung Shwe , Kee Yuan Chuan , Ho Han Kiat , Fan Gilbert , Yong Wei Sean , Madhukumar Preetha , Ooi Wei Seong , Chay Wen Yee , Ng Raymond C.H. , Ng Quan Sing , Ang Soo Fan , Lo Soo Kien , Yap Yoon Sim , Dent Rebecca Alexandra , Chan Alexandre
Published: March 2020

e20566

Background: It is suggested that vascular endothelial growth factor (VEGF) induces neurogenesis in the brain and provides neuroprotectiveeffects. This study was designed to examine the relation between plasma VEGF level and cognitive functioning in breast cancer patients who have received chemotherapy. Methods: Early-stage breast cancer patients (stage I to III) who received anthracycline- and/or taxane-based chemotherapy were prospectively recruited at a single center. Perceived cognitive functioning (FACT-Cog) and computerized neuropsychological assessment (Headminder) were used to evaluate patients’ cognitive function at three time points: prior to chemotherapy (T1), at midpoint (T2), and end of chemotherapy (T3). Headminder evaluated four cognitive domains: Attention, Memory, Processing, and Response speed. Impairment in each domain were defined as a >2.5 reduction of the Z score from baseline, as calculated by the reliable change index for repeated cognitive measurements. Plasma VEGF levels were analyzed at each time point using the multiplex immunoassay. Spearman Correlation (rs) was utilized to correlate the change in plasma VEGF and neurocognitive functioning. Results: Thirty-six patients were recruited (median age: 51.5; Chinese: 80.6%; post-menopausal: 58.3%). Median plasma VEGF levels were T1: 19.2 pg/ml; T2: 26.5 pg/ml; T3: 21.9 pg/ml. Weak correlations were observed between the change in VEGF level and the change in FACT-Cog and Headminder scores for individual cognitive domain (Table). Conclusions: Results suggest a weak correlation between plasma VEGF level and cognitive functioning in the domains of attention, concentration, functional interferences, mental acuity and response speed. Larger sample size and longer follow up are required to further explore the findings. [Table: see text]
Recovery of complete antiemetic response with APF530 during treatment with moderately (MEC) and highly (HEC) emetogenic chemotherapy regimens in patients who failed palonosetron.
Authors: Arevalo-Araujo Roberto , O'Boyle Erin , Cooper William , Robertson Paul Alexander
Published: March 2020

e20569

Background: Several 5-HT3 antagonists are available to prevent chemotherapy-induced nausea and vomiting (CINV); when control is inadequate with one agent, another may be used. Using data from a randomized phase III trial (Grous et al. ASCO 2009, #9627), we examined the efficacy of APF530, a sustained delivery formulation of the 5-HT3antagonist granisetron, in patients (pts) who failed to achieve a complete response (CR; no emesis or rescue medication) with palonosetron (PALO) in preventing acute (0-24 h) and delayed (24-120 h) CINV in pts receiving MEC or HEC. Methods: 1,428 pts receiving single doses of MEC or HEC were randomized to APF530 250 mg (5 mg granisetron) subcutaneously (SC), APF530 500 mg (10 mg granisetron) SC, or PALO 0.25 mg intravenously (IV) in cycle 1 (C1). Prior to C2, pts who received PALO in C1 and remained on study were re-randomized to APF530 250 mg or 500 mg SC. CR rates in C2 were assessed for pts receiving APF530 500 mg who did not achieve CR in C1 with PALO. Results: 446 pts received PALO in C1 (208 MEC; 238 HEC). Of these, 194 (43.5%) were overall (0-120 h) failures (100/208 [48.1%] MEC; 94/238 [39.5%] HEC). Of 194 C1 PALO failures, 72 were re-randomized prior to C2 to APF530 500 mg (38 MEC; 34 HEC). Of 38 MEC PALO failures who received APF530 in C2, overall CR was 39.5% (57.9% acute; 38.2% delayed). Of 34 HEC PALO failures who received APF530 in C2, overall CR was 41.2% (58.3% acute; 45.5% delayed). In the acute phase, > 50% of MEC and HEC pts who failed PALO in C1 achieved CR to APF530 500 mg in C2. CR rate for pts receiving MEC or HEC was slightly less in the delayed vs acute setting. Conclusions: APF530 500 mg demonstrated substantial activity (ie, CR) in pts receiving MEC or HEC who had failed PALO in C1. Failure to achieve an initial CR to PALO 0.25 mg IV does not predict failure of APF530 500 mg SC in subsequent MEC or HEC cycles. Further studies are needed to confirm these observations. Clinical trial information: NCT00343460. [Table: see text]
A randomized trial of a nurse-led decision aid to inform patients with advanced cancer about palliative chemotherapy.
Authors: Ottevanger P. B. , Oostendorp Linda JM , Van Der Graaf Winette T.A. , Stalmeier Peep FM
Published: March 2020

e20583

Background: There is a lack of decision aids (DAs) for patients with advanced cancer considering palliative treatment. In this randomized study, we evaluated nurse-led DAs about second-line palliative chemotherapy for patients with advanced breast (BC) or colorectal cancer (CRC). Methods: Patients with advanced BC or CRC considering second-line treatment were randomized to receive only usual care (control group) or usual care plus a DA from a nurse (intervention group) (1:2 ratio). Using the DA, a nurse offered information on adverse events, tumor response, and survival. Patients completed a baseline questionnaire and two follow-up questionnaires 1 week and 8 weeks after the treatment-related information was provided. Outcome measures were well-being, coping, knowledge, and information and decision-related outcomes. Intent-to-treat analyses were performed using Chi Square tests, independent samples t-tests, and linear mixed models to examine differences between groups over time. Results: In all,128 patients participated in the study; median age 62 years (range 32-81), 37% male, 73% CRC. Of the 83 patients assigned to the intervention group, 77 received a DA. At the first follow-up, more patients receiving a DA preferred chemotherapy (96% vs. 84%; p=0.067). Seven weeks later, 88% of patients in the intervention group and 84% of patients in the control group had started chemotherapy (p=0.746). The only statistically significant effect was the stronger treatment preference of patients in the intervention group (3.0 vs. 2.5; p=0.030). The DAs did not negatively impact anxiety, depression, cancer worries, and hopelessness. Conclusions: It is possible to offer a DA with explicit information to patients with advanced cancer without negative impact on patients' well-being. Unexpectedly, this study did not show consistent effectiveness of the DAs. Our interpretation is that most patients receiving the DA had already decided to start chemotherapy. Clinical trial information: NTR1113.
Palliative benefit of novel cell-free and concentrated ascites reinfusion therapy (CART) for refractory ascites associated with cancerous peritonitis.
Authors: Matsusaki Keisuke , Yoshizawa Akitaka , Ohta Keiichiro
Published: March 2020

e20591

Background: Refractory ascites associated with cancerous peritonitis causes severe abdominal distention, dyspnea and appetite loss, resulting in loss of patients’ activities of daily living (ADL) and discontinuation of their treatment for cancer such as chemotherapy. To improve the symptoms, we have developed a novel cell-free and concentrated ascites reinfusion therapy (CART) which is modified from a conventional CART approved by the Ministry of Health, Labor and Welfare in Japan and examined the efficacy in a pilot study. Methods: 87 patients with cancerous ascites were enrolled and subjected to novel CART from April 2012 to November 2012. The response was assessed by improvement of their ADL. Patients were asked in the form of questionnaires about general malaise, abdominal distention, abdominal pain, nausea, dyspnea, sleep disturbance, appetite loss, disturbance in gait, discomfort and frustration before and after treatment and each point was scored on a scale of zero to ten (ten being severe). Abdominal and thigh circumferences were also examined before and after treatment to evaluate efficacy. This study was approved by the ethics review committee of Kaname-cho hospital. Results: On average, 8.3 ± 4.4 L (range 2.3-27.0) of cancerous ascites was filtrated and concentrated to 0.69 ± 0.28 L (range 0.2-1.6) by novel CART. Any severe adverse events except fever were not observed. After treatment, the scores of all points were significantly improved. For example, abdominal distention was improved by 8.1 ± 2.4 vs. 2.0 ± 2.4 (p<0.0001), dyspnea by 3.7 ± 3.3 vs. 1.3 ± 2.1 (p<0.0001), and appetite loss by 5.3 ± 4.3 vs. 3.1 ± 3.4 (p<0.0001). Abdominal and thigh circumferences were also decreased by -13.3 ± 7.5 cm (p<0.0001) and -2.7 ± 2.6 cm (p<0.0001), respectively. Conclusions: This novel CART system is capable to process over 20 L of cancerous ascites and immediately improve their ADL and edematous lesions. Some patients also restarted anticancer treatment such as chemotherapy. Taken together, this CART is safe and effective for palliative care of patients with cancerous ascites.
Clinical experience with uridine triacetate for 5-FU overexposure: An update.
Authors: Bamat Michael K. , Tremmel Robert , von Borstel Reid , Helton Joan
Published: March 2020

e20592

Background: 5-Fluorouracil (5-FU) is broadly used to treat solid tumors. It is typically administered by IV infusion, at or near its maximum tolerated dose, over several days. The use of infusion pumps increases the possibility of life-threatening or lethal toxicity due to errors in pump programming, infusion reservoir errors and dosage miscalculations. Partial or total dihydropyrimidine dehydrogenase (DPD) deficiency, which predisposes patients (up to 3% of the population) to impaired 5-FU elimination, can also result in serious or lethal toxicity, Uridine triacetate is an orally bioavailable direct biochemical antagonist of 5-FU toxicity that has been used successfully to treat patients in emergency overdose situations as well as patients with known or suspected overexposure to 5-FU due to DPD deficiency or other causes. Approximately 100 patients at excess risk of 5-FU toxicity due to 5-FU overdose, accidental Xeloda (capecitabine) ingestion, or possible DPD deficiency (rapid onset of severe toxicities) have been treated with uridine triacetate using a common treatment regimen and protocol. More than 80 of these cases have occurred since uridine triacetate data were presented at ASCO in 2009. Methods: Uridine triacetate was provided under emergency IND provisions or an expanded access protocol when requested by qualified clinical sites following 5-FU overexposures, most due to infusion pump errors. Patients received uridine triacetate (10g q6h for 20 doses) as soon as possible after recognition of the overdose or possible clearance defect. Clinical outcomes, including safety and resumption of chemotherapy, were monitored. Results: To date, 98 patients overexposed to 5-FU have been treated with uridine triacetate. 96 of these 98 patients recovered fully. Reductions in or absence of GI, hematologic, and other toxicities associated with 5-FU poisoning were observed. Adverse events attributable to urdine triacetate were infrequent and mild in severity. Conclusions: Uridine triacetate appears to be a safe and effective life-saving antidote for 5-FU overexposure in emergency situations.
Are validated symptom assessment instruments comprehensive? “Orphan” and “champion” symptoms.
Authors: Thomas Shirley , Walsh Declan , Aktas Aynur
Published: March 2020

e20597

Background: Cancer patients experience multiple symptoms which vary in prevalence, severity, distress and negative impact on life. Comprehensive assessment is essential. Many validated assessment tools are used. They have limitations; varied content, clinical utility, completion rates, and acceptability. The objectives of this study were: Compare common cancer multisymptom assessment instruments to a comprehensive checklist. Identify commonly assessed (“champions”) and frequently neglected (“orphans”) symptoms. Examine the clinical importance of “orphan” symptoms. Methods: A 46-symptom checklist was developed from available evidence. This was compared against the content of 6 commonly used, validated, multisymptom instruments. Those with ≤ 2 symptoms, cancer site-specific, and tumor response instruments were excluded. Results: Symptom numbers varied in the 6 instruments; median (range) 19 (3-32). Of the 46 checklist symptoms, only 28 were present in 1 or more of the instruments. “Orphans”: 18 of the 46 were not evaluated in any of the 6 (e.g., confusion, agitation, early satiety, indigestion, tremors). 12 of the 18 had prevalence rates >10%. These symptoms are also often rated moderate/severe and distressful. “Champions”: Only four checklist symptoms (pain, fatigue, dyspnea, anorexia) were present in all 6 instruments. Conclusions: Eighteen “orphan” symptoms (severe/distressing) were not captured by any tool. Only four “champion” symptoms were present in all validated tools. Unreported and misdiagnosed symptoms can bias our view of the cancer symptom experience. Validated cancer symptom assessment tools do not capture accurate, reliable comprehensive data on the cancer symptom experience. These challenge the validity and reliability of current symptom assessment tools in clinical research.
Risk of proteinuria with the new angiogenesis inhibitor axitinib in patients with cancer.
Authors: Kuei Andrew , Zhu Xiaolei , Wu Shenhong
Published: March 2020

e20602

Background: The use of axitinib, a potent inhibitor of vascular endothelial growth factor receptor (VEGFR), is associated with proteinuria, which may cause morbidity and treatment interruptions in cancer patients. We performed a systematic review and meta-analysis of published clinical trials to assess the overall risk of proteinuria with axitinib. Methods: Potentially relevant studies were identified by searching databases including Pubmed and abstracts presented at the American Society of Clinical Oncology annual meetings until June, 2012. Eligible studies included prospective clinical trials in cancer patients treated with axitinib containing data on proteinuria. Summary incidence, relative risk (RR), and 95% confidence interval (CI) were calculated using the fixed- or random-effects models. Results: A total of 1,671 patients with advanced renal cell carcinoma (RCC) and other solid tumors from 9 studies were included for analysis. The overall incidences of all-grade and high-grade (grade 3 or 4) proteinuria with axitinib were 22.7% (95% CI: 10.4-42.6%) and 3.8% (95% CI: 2.6-5.7%) respectively. The risk did not vary significantly with tumor types (P=0.13). There was no significant difference between RCC and non-RCC patients (P=0.45), although the incidence in RCC patients was higher (30.0%, 95% CI: 8.4-66.7 versus 17.5%, 95% CI: 7.4-36.3%). In comparison with a control (gemcitabine), axitinib significantly increased the incidence of high-grade proteinuria (3.3%, 95% CI: 1.6-6.5% versus 0.1%, 95% CI: 0-2.3%; P=0.031). When compared to another angiogenesis inhibitor sorafenib, axitinib did not have a significantly higher risk of all-grade (RR=1.48, 95% CI: 0.92-2.38, P=0.10) and high-grade proteinuria (RR=1.81, 95% CI: 0.68-4.85, P=0.24). Conclusions: There was a significant risk of proteinuria associated with the use of axitinib in cancer patients.
The effect of oral β-glucan on mucositis and leukopenia in colorectal cancer patients receiving adjuvant FOLFOX-4 combination chemotherapy.
Authors: Karaca Halit , Berk Veli , Inanc Mevlude , Dikilitas Mustafa , Ozkan Metin
Published: March 2020

e20603

Background: β-glucans have antibacterial, immunomodulator and anti-cancer effects. The present study aimed to determine the effect of oral β-glucan on mucositis and leukopenia in a group of colorectal cancer patients with a high risk for neutropenia and mucositis who received adjuvant FOLFOX-4 (oxaliplatin, 5-flourouracil, and folinic acid) combination chemotherapy. Methods: This retrospective study included 62 patients with colorectal cancer that underwent a FOLFOX-4 treatment regimen between July 2009 and July 2010. Ethics committee of Erciyes University approved the study design. Colorectal cancer patients treated with a FOLFOX-4 regimen were retrospectively evaluated in 2 equal groups: One group received β-glucan (treatment group), and the other did not (control group). In both groups the level of leucocytes, neutrophils, and platelets were evaluated before and 1 week after chemotherapy. The occurrence of oral mucositis and diarrhea was noted. Data were statistically analyzed. Results: There were 21 male and 10 female patients in the treatment group, and the median age was 61 years (range: 43-72 years). The control group included 17 male and 14 female patients, and the median age was 55 years (range: 30-78 years). There weren't any statistically differences in age or gender between the 2 groups. Leucocyte and neutrophil counts after chemotherapy in the treatment group were 7300/mm3 and 3800/mm3, respectively, and the reductions, as compared to baseline, were not significant (p = 0.673 and 0.784). The median platelet count was 264000/mm3 after chemotherapy in the treatment group and the reduction, as compared to baseline, was borderline significant (p = 0.048). In the control group the reduction in leucocyte, neutrophil, and platelet counts was statistically significant (median values were 5600/mm3, 2880/mm3, and 229000/mm3, respectively; p < 0.01). In addition, oral mucositis and diarrhea secondary to chemotherapy were less common in the treatment group (19% v.s 42%). Conclusions: β-glucan effectively suppressed the adverse effects of chemotherapy. We think that nutritional supplementation with β-glucan in cancer patients should be investigated further.
Effects of animal-assisted visits on quality of life during multi-modal radiation therapy: Chemotherapy regimens.
Authors: Fleishman Stewart Barry , Rosenwald Victoria , Homel Peter
Published: March 2020

e20607

Background: Animal-assisted visits (AAV) are known to affect blood pressure, mood and anxiety, yet their effects in cancer remained unexamined. Methods: 42 subjects signed IRB-approved informed consent to have AAVs daily during multi-modal chemotherapy and radiation therapy for head & neck cancer. 37 subjects completed at least baseline assessment visits for an intent to treat analysis. Assessments included FACT-Head and Neck scale; Satisfaction with AAV Intervention (SAAVI) assessing bi-weekly motivation to attend appointments, tolerance of waits, ability to withstand treatment, lingering effect of AAV after treatment and perception of social support. Subject characteristics: 25 (68%) male, mean age 57 years (57.22 ±8.44); (57%) white, 8 (22%) Hispanic, 6 (16%) black and 2 (5%) Asian. Cancer sites: oropharynx 23 (62%), hypopharynx 4 (11%), esophagus 3 (8%), laryngopharynx 2 (5%) and nasal cavity 2 (5%). Stage: stage II: 1 (3%), III: 6 (16%), IV: 30 (81%). All subjects received concomitant external beam radiation therapy with periodic cis-platin (23 pts, 57%), weekly carboplatin (7 pts; 16%) or cetuximab (5; 11%). Results: Comparing baseline, week 3 and week 7 assessments, FACT Physical Well-being (PWB; p<0.001) and Functional Well-Being (FWB; (p=0.003) showed significant declines; in contrast, Social Well-Being (SWB; p = 0.03) showed significant gains. Controlling for declines in PWB, increases in EWB were also significant (p = 0.004). Satisfaction was measured after the first and last AAV. Mean scores for satisfaction related to psychological symptoms, generally liking animals/pets, and positive attitudes towards pets at both times were significantly better than “Neutral” or “Unsure” (all p < 0.001), and did not change from first to last AAV. Mean scores for physical symptoms were not significantly different from “Neutral.” Conclusions: FACT analysis showed significant increase in EWB in the face of clinically evident and expected declines in PWB and FWB in spite of high symptom burden. The SAAVI assessment further supports the utility of the AAV intervention. Though self-selected for an affinity to pets and animals, subjects endorsed a high level of satisfaction with the intervention.
Assessment of the current implementation and barriers to uptake of the guidelines for the psychosocial care of adults with cancer according to cancer nurses in Australia.
Authors: Lawsin Catalina , McMillan Kirsty , Butow Phyllis , Turner Jane , Yates Patsy , Stephens Moira , Lambert Sylvie D. , White Kathryn
Published: March 2020

e20615

Background: The Clinical Practice Guidelines for the Psychosocial Care of Adults with Cancer (the Guidelines) were launched in 2003 to guide cancer care providers in the assessment of psychosocial issues and provision of evidence-based interventions. Despite multi-faceted Australia-wide dissemination efforts, the current study aimed to be the first to assess current implementation of the Guidelines across and barriers to uptake. Methods: A cross-sectional web-based survey was developed to assess clinical use of recommendations in the Guidelines in relation to the provision of psychosocial support, and assessment of distress and pain. Data was collected about perceived barriers to the provision of psychosocial support at participants’ place of employment, as well as roles and training needs. Cancer nurses were recruited through the Cancer Nurses Society of Australia, the Royal College of Nursing Australia, and the Haematology Society of Australia & New Zealand. Descriptive and correlational analyses were conducted. Results: Of 354 respondents, 266 completed the assessment. Relaxation training was the most prevalent form of psychosocial support (24%) and web-based support (20%) was the most common modality. While 26% of institutions had no systematic means of assessing distress amongst patients, those that did relied primarily on clinical interviews (37%). Once a patient was identified as distressed, most often the care coordinator was responsible for providing ensuing interventions. An organizational culture in which psychosocial issues are seen as less important than medical treatment (23%) and role ambiguity proved to be barriers to provision of psychosocial support, particularly when nurses did not perceive psychosocial support was beneficial and supervision was inadequate (R2= .313, F(1, 265) = 6.58, p < .001). Conclusions: Results confirmed that dissemination does not necessarily equal implementation. Clear pathways for assessment and treatment need to be established to reduce individual barriers and promote organizational cultures that appreciate the need to integrate psychosocial care in standard medical treatment.
End-of-life care planning in patients with recurrent gynecologic cancers.
Authors: Jones Nathan L , Galvin Shelley L , Vanderkwaak Timothy J , Hetzel David J. , Harkness Cameron Blair , Case Ashley S
Published: March 2020

e20648

Background: Gynecologic oncologists and associates must provide appropriate, acceptable, and patient-centered end-of-life care. Most women with terminal gynecologic cancers do not have do-not-resuscitate (DNR) orders upon hospital admission and many do not receive effective palliative care. Our objective was to assess quality care indicators involving end-of-life care among gynecologic oncology patients treated at our institution. Methods: An IRB-approved retrospective chart review was performed on all patients with recurrent gynecologic cancers and terminal diagnoses who died from January 2009 through October 2012. Data included intervals to death from: diagnoses, DNR status, Hospice/Palliative Care Medicine (HPCM) involvement, and other factors related to end-of-life care. Chi-squared and discriminate analyses were utilized. Results: Complete data were available for 130 of 345 (37.7%) patients. Disease sites included cervix 28 (21.5%), uterine 37 (28.5%), ovarian 51(39.2%), and vaginal/vulvar 14 (10.8%). Median age at diagnosis and death was 63 and 65 years. Relative to death, diagnoses occurred at a median of 1.65 (0.05-32) years prior. 83 (63.8%) patients were DNR at their last hospitalization, 84(64.6%) had HPCM involvement, and 18(13.8%) had an advance care plan. When HPCM was involved, 83.3% were DNR as compared to 28.3% without involvement (p=0.0001). Patients were also significantly more likely to have DNR status with diagnosis of ovarian cancer and as the duration of time between diagnosis and death increased (p=0.0001). The provider obtaining DNR was most often faculty over residents or HPCM (60.2%, 27.7%, 12%). DNR status was declared by 57 (68.7%) patients and 26 (31.3%) power of attorneys. Median duration from DNR to death was 14 days (0-308) and median duration from HPCM involvement to death was 22 days (0-391). Conclusions: DNR status is associated with ovarian cancer, HPCM involvement, and increasing time from diagnosis to death. Earlier intervention from providers or HPCM could allow for greater patient autonomy and fewer interventions at end-of-life.
A new molecular diagnostic tool for pneumocystis jirovecii-pneumonia (PjP) detection: Results from European multicenter clinical study CS-2011.
Authors: Karrasch Matthias , Schulte Berit , Autenrieth Ingo , Denis Olivier , Torres Antoni , Knabbe Cornelius , Luedke Gerd , Straube Eberhard , Keller Peter M. , Weile Jan
Published: March 2020

e20652

Background: Pneumocystis pneumonia (PCP) is a frequent and serious infectious complication in tumor patients. PCP is caused by Pneumocystis jirovecii, a fungal pathogen which is uncultivable in vitro. Highly-sensitive and time-efficient diagnostic tools are needed for early PCP treatment, especially in patients with impaired immune status. Methods: We evaluated a prototype of a new non-invasive molecular diagnostic tool (Unyvero System) using polymerase chain reaction (PCR) for P. jirovecii detection in respiratory samples (bronchoalveolar lavage fluid, tracheal aspirates, sputum) of hospitalized patients suffering from pneumonia. Results were obtained in an open-label, multicentric, non-randomized clinical study (CS-2011) conducted in 5 European hospitals. Unyvero system test results were compared to study site specific PCR results for P. jirovecii detection. Discrepant results were analysed for clinical relevance of molecular diagnostic tool results. Results: P. jirovecii was detected in 11 patients (1.49 %) out of 739 evaluable study patients: Of these, 8 cases (1.08 %) were detected only with the Unyvero System, 2 cases only with site-established techniques and 1 case with both methods. An independent academic cross-check of these 8 Unyvero System -positive cases showed that 5 cases were false positives due to signal reading failure. The remaining 3 cases could be confirmed as true positives by control PCP-PCR, indicating Unyvero P. jiroveciidetection results of 2 false negatives, 4 true positives and 5 false positives. Conclusions: The overall detection rate for P. jirovecii was low (11 out of 739) in this study population. Although more positive cases were found using the Unyvero System, it remains unclear if this was of clinical significance, especially as two clinically confirmed PCP cases could not be detected. The Unyvero System prototypes had a rate of 0.7% false positive results (5 out of 739 samples) which might have led to an overtreatment under real conditions. However, the correct detection of 4 positive cases within 3 hours might render the Unyvero System a valuable diagnostic future tool.
Trends in the use of bone agents in metastatic cancer.
Authors: Kogler Jurgen Wilhelm , Hrushesky William J. , Huff Dinah , Bobolts Laura Rose , Kumar Akhil , Shimp William S. , Krook James Edward , Fishman Val , Davis Sharon , Anthony Carol , Walton Robert , Fishman Marc L.
Published: March 2020

e20672

Background: Bone modifying agents have been shown to delay and/or prevent skeletal-related events for a range of cancers metastatic to the bone. Various studies have identified pamidronate, zoledronic acid, and denosumab as bone modifying agents, each of which confers clinical benefit. The convenience of administration and costs of these agents differ greatly. Administration spans vary from roughly 2 hours for IV pamidronate, 15 minutes for IV zoledronic acid, and minimal time for subcutaneous denosumab. The estimated cost for a single dose of pamidronate, zoledronic acid, and denosumab are $29, $890, and $1,712, respectively. Methods: All requests for pamidronate, zoledronic acid, and denosumab authorization submitted by practicing oncologists within southeast Florida were tabulated for 2010, 2011, and 2012. Comparisons for both frequency of use and cost over time were made using ANOVA and Chi Square; p<0.05 for significance. Trends were assessed by linear regression. Results: 895 requests for pamidronate, zoledronic acid, or denosumab were examined over this three year span. The use of bone modifying agents for metastatic cancer is increasing rapidly, as treatment request totaled 171, 269, and 455 for all three agents, pamidronate, zoledronic acid, or denosumab, in 2010, 2011, and 2012, respectively. Zoledronic acid requests significantly increased (p<0.001) per year between 2010 and 2011, as with 2011 and 2012. Denosumab requests are also increasing steadily and sharply in 2012. Conclusions: Each of these three agents has demonstrated clear efficacy in delaying or preventing second skeletal events among patients with metastatic cancer already involving bone. Toxicities among these three agents are comparable in the vast majority of eligible cancer patients. Relative costs should be carefully considered when choosing which agent to use as the use of these agents in general is increasing rapidly and will have a major impact upon overall cancer care costs. [Table: see text]