bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minocycline to reduce cancer pain in patients with multiple myeloma: A phase II randomized trial.
Authors: Wang Xin Shelley , Cleeland Charles S. , Shi Qiuling , Prasad Seema , Bokhari Raza H , Orlowski Robert 
Published: September 2018

10100 Background: Patients with multiple myeloma (MM) experience substantial pain that may be from disease and/or post autologous stem cell transplant condition, and exacerbated by maintenance therapy. Minocycline is a readily available, low-cost antibiotic with anti-inflammatory properties. We conducted a phase II randomized, double-blinded, placebo controlled clinical trial to investigate the effect of minocycline in reducing patient-reported symptoms during maintenance therapy. Methods: Adults with MM scheduled for maintenance therapy at a single-institution were consented and randomized to receive either minocycline (100 mg twice daily) or placebo over the first 3 cycles maintenance therapy. Feasibility, toxicity, and patient-reported outcome data were prospectively collected. The MD Anderson Symptom Inventory-MM (0–10 scale) was used to assess pain and other symptoms weekly during 3 months trial. The longitudinal analysis for pain was compared between the minocycline and control groups to examine minocycline’s efficacy. Results: From April 2013 to Aug 2016, 88 patients were enrolled and 69 (78%) were evaluable: 33 were randomized to minocycline and 36 to placebo. There were no grade 3+ study medication-related adverse events. The worst 5 symptoms on MDASI-core during the trial were fatigue, pain, numbness/tinging, drowsiness, and disturbed sleep, followed by two MM module item bone aches and muscle weakness. Demographic and disease characteristics were not significantly different between groups. Longitudinal modelling of revealed a significant reduction on pain in minocycline group than placebo group (time and treatment group interaction, estimate=-0.068, P=.003). The favorite pain reduction in minocycline group vs placebo arm was represented by a moderate effect size (Cohen’s d =0.48). Conclusions: Minocycline during maintenance therapy for MM was feasible, had a low toxicity profile, and yielded a statistically significant positive signal on pain reduction. These preliminary results are encouraging and warrant a Phase III trial to test its efficacy. Clinical trial information: NCT01793051.
Phase II study of the effect of the topical corticosteroid fluocinonide in patients on endocrine therapy for breast cancer or breast cancer prevention with symptoms of vaginal dryness and dyspareunia.
Authors: Hobbs Evthokia A. , Lethert Kristine , Nauman Deirdre J. , Bucher Jenna , Latour Emile , Mori Motomi , Chui Stephen Y. , Kemmer Kathleen A. 
Published: September 2018

10105 Background: Gynecologic symptoms and sexual dysfunction from endocrine therapy are troublesome side effects for a significant number of patients. This study explored amelioration of vaginal dryness and dyspareunia with fluocinonide cream, a strong topical corticosteroid. Methods: A single-arm, open-label phase II trial of topical fluocinonide 0.05% cream to improve vaginal symptoms in women on endocrine therapy in the adjuvant setting for early stage breast cancer was performed. Patients with vaginal symptoms applied topical vaginal fluocinonide 0.05% cream twice a day for two weeks then once daily for two weeks. Patients were assessed for symptoms by weekly completion of the Mayo/North Central Cancer Treatment Group Patient Pretreatment Questionnaire. The primary outcome was a change from baseline in patient-reported effects of vaginal dryness and dyspareunia on a scale from 0 (no symptoms) to 4 (very severe symptoms) from time of enrollment and at 4 weeks. Secondary outcomes were decrease in vaginal itching and total vaginal index score. Comparisons were made with Wilcoxon sign rank test with 2.5% significance level. Results: Thirty-four women were accrued. At 4 weeks compared with baseline, vaginal dryness improved from a median score of 2 (moderate symptoms) to 0 (no symptoms) ( P < .001) and dyspareunia from 3 (severe symptoms) compared with 1 (mild symptoms) ( P = .002). Percentage of patients who had > 2 point improvement in vaginal dryness and dyspareunia was 69.0% and 75% respectively. Secondary analysis showed decrease in vaginal itching score from 1 to 0 ( P = .001) and vaginal index score of 6 to 1 ( P = .002). Twenty-one patients experienced low-grade toxicities which were mostly limited to skin irritation. Conclusions: Fluocinonide 0.05% cream improves vaginal dryness and dyspareunia experienced by women receiving endocrine therapy and has the potential to improve quality of life of cancer survivors and compliance of endocrine therapy. Clinical trial information: NCT00297011.
The impact of caregiver’s role preference on decisional conflicts and psychiatric distresses in decision making to help caregiver’s disclosure of terminal disease status.
Authors: Yoo Shin Hye , Yun Young Ho , Kim Kyoung-Nam , Lee Jung Lim , PARK Jeanno , Choi Youn Seon , Lim Yeun Keun , Kim Samyong , Jeong Hyun Sik , Kang Jung Hun , Oh Ho-Suk , Park Jichan , Kim Si-Young , Song Hong-Suk , Lee Keun Seok , Heo Dae Seog , Hong Young Seon 
Published: September 2018

10106 Background: A decision aid (DA) increases knowledge, decreases decisional conflicts and regrets and improves post-decision satisfaction, emotional distress. However, few DA trials have revealed whether decisional role preferences have an impact on patient-reported outcomes by decision making. The objective of this study was to investigate the impact of caregiver’s decisional role preference on decisional conflicts and psychiatric distresses in decision making. Methods: 406 of 444 caregivers of terminally ill cancer patients enrolled onto a previous trial determining the efficacy of the decision aid about disclosure of terminal disease status were included in this analysis. The analysis outcomes were change score of decisional conflicts using the Decision Conflict Scale (DCS) and depression and anxiety using the Hospital Anxiety and Depression Scale (HADS) at 1 and 3 months from baseline. Participants were divided into 4 groups: active caregiver who received DA (active-DA), active caregiver in control group (active-control), passive caregiver who received DA (passive-DA), and passive caregiver in control group (passive-control). Linear mixed model was conducted to find out the impact of caregiver’s decisional role preference on the DCS and the HADS. Results: Among 406 caregivers, 137 (33.7%) showed active role preference, and 269 (66.3%) showed passive role preference. In post-hoc analysis of adjusted differences of change scores between passive-DA and active-DA groups, non-significant differences were observed in DCS. However, at 3 months, change scores of HADS depression subscale increased as 4.43 (95% confidence interval (CI), 0.78-8.07; P< 0.007; effect size (ES) 0.71) and those of HADS anxiety subscales increased as 4.14 (95% CI, 0.37-7.91; P= 0.021; ES 0.61) in passive-DA group than in active-DA group, showing moderate to large difference. Conclusions: These findings suggest that information about decision making might be provided with tailored format for how much individual wish to involve in decision making.
Biomarker to cost-effectively harness the technical prowess of palliative radiation: Neutrophil lymphocyte ratio (NLR) and overall survival following palliative radiotherapy in an unselected real-world population of all tumor sites.
Authors: Sundar Santhanam , Price James , Clarke Kirsty , Wolfe Thomas , Thurairasa D , Shawcroft Ewan 
Published: September 2018

10111 Background: Single fraction radiotherapy (RT) is standard of care for palliation of pain from bone metastases (ASTRO IJROBP 2011 79:965). But costly, complex, multi-fraction RT is quite often used for palliation of symptoms from various organs. Health care costs are burgeoning (ASCO JCO 2012 30: 1715). Costs can be constrained by judiciously reducing use of unnecessary multi-fraction RT in pts with limited life expectancy. But radiation oncologists’ ability to predict survival is inaccurate. (Chow IJROBP 2005 61:870). Hence we assessed clinical utility of Neutrophil Lymphocyte ratio (NLR) - a routinely available biomarker. Methods: 233 patients (pts) undergoing palliative RT over a 3 month at Nottingham University Hospital. Predominant Tumour SITES: Lung 28% Breast 13% Prostate 13% Colorectal 9% Gastro-Oesophageal 5% Myeloma 5% Bladder 5%. Predominant HISTOLOGY: Adenocarcinoma 61% Squamous Cell 14%. NLR available for 158 pts. Results: A NLR of 4.5 was highly predictive of 90-day mortality & overall survival in an unselected real world population. (Table). No survival benefit seen for multi-fraction RT over single fraction RT across all tumour sites. On survival analysis by Cox regression, increased NLR was significant with a hazard ratio of 2.2 (95% CI 1.3 to 3.7) whereas total radiation dose, use of multiple fractions , age, serum haemoglobin, serum albumin & histology were not significant. Conclusions: In palliative care of advanced cancer, for pts with high NLR (>4.5), Single fraction RT should be the standard of care for palliation of symptoms. [Table: see text]
Safety and efficacy of same-day administration of pegfilgrastim in patients (pts) receiving chemotherapy for gastrointestinal (GI) malignancies.
Authors: Matera Robert M. , Relias Valerie , Saif Wasif M. 
Published: September 2018

10112 Background: Pegfilgrastim is typically administered 24 hours after chemotherapy per package insert; however some pts are unable or unwilling to return for this additional visit due to work or transportation especially with regimens consisting of infusional 5-FU. Same-day dosing eliminates need for this additional visit. Results from prior studies in other tumor types are inconclusive as few support same-day dosing whereas others show inferiority. Purpose of our study was to determine safety and efficacy of administering pegfilgrastim on same day as chemotherapy in pts with GI malignancies. Methods: A single-institution retrospective review was conducted of pts with GI malignancies who received chemotherapy and same-day pegfilgrastim (6 mg) within 1 hour of completion of chemotherapy from Jan 2014 through Jan 2017. Decision to administer pegfilgrastim was based on NCCN or ASCO recommendations. As per institutional guidelines, pts were counseled on risks of same-day pegfilgrastim prior to its administration. Data was collected on demographics, clinic notes and complete blood counts. Analyses included neutropenia, febrile neutropenia, hospitalization, use of antibiotics or bone pain. Results: A total of 536 chemotherapy cycles in 69 pts were analyzed. Median age was 60 years (range 32-87) with 46% of pts ≥ 65. Pts had an average of 4 risk factors for febrile neutropenia: advanced disease, gender, age > 65 and chemotherapy regimen. Most common malignancy was colon (48%), pancreas (17%) and gastric (17%). Most commonly used regimens included mFOLFOX6 (42%), FOLFIRINOX (23%) and FOLFIRI (12%). Median absolute neutrophil count nadir for all cycles was 4538/uL (range: 1160-25168). Grade 1 and 2 neutropenia developed in 6 of 536 (1%) cycles. Bone pain reported in 3 pts (4%). There were no episodes of grade 3 or 4 neutropenia or febrile neutropenia. None had dose reductions, chemotherapy delays, hospitalizations, or antibiotic use due to neutropenia. Conclusions: We believe our study is the first in GI malignancies to report that same-day pegfilgrastim administration may be as effective and safe as next-day administration, benefiting pts and might reduce costs.
Anticipative monitoring to improve chemotherapy induced nausea.
Authors: Elaidi Reza , Oudard Stephane , Aboudagga Hail , Thibault Constance , Waechter Lorraine , Stevens Jerome , Bonan Brigitte , Scotte Florian 
Published: September 2018

10120 Background: The PROCHE [Programme for optimisation of the chemotherapy network] initiative is an innovative oncology-monitoring program designed to reduce patient waiting time and chemotherapy wastage, ultimately improving patient care. Methods: Primary objective was to evaluate the incidence of nausea reported by grade (NCI-CTC AE: from 0 to 4) from 2008 to 2016. Association was quantified using Mantel-Haenszel khi2 and exact p-values. Secondary objective compared the 2009-2016 patients with the control patients of 2008 period. Results: Between Oct 2008 and Oct 2016, 3012 patients participated in the program, representing 36 803 questionnaires completed over the whole period. Nausea was, clinically and statistically, significantly improved during the whole follow-up period with a decrease of grade 3-4 from 0.6% to 0.08% and a decrease of grade 1-2 from 29.3% to 8.2%. The already adapted nausea management in 2008 with 70% of questionnaires reported no nausea improved to 92% in 2016, with a 10% improvement the year after program initiation. As MASCC propose to change guidelines with an improvement above 10%, such an organization may impact new recommendations. Conclusions: Anticipating anti-cancer treatment adaptation and prevention, following guidelines and using adapted antiemetics, explain these positive results. The PROCHE initiative improves chemotherapy induced nausea. [Table: see text]
Advanced cancer patients' self-reported perception of timeliness of their referral to outpatient supportive/palliative care and their survival data.
Authors: Wong Angelique , Hui David , Epner Margeaux , Balankari Vishidha Reddy , De la Cruz Vera J , Frisbee-Hume Susan , Cantu Hilda , Perez Zapata Kresnier , Liu Diane D , Williams Janet L. , Bruera Eduardo 
Published: September 2018

10121 Background: Palliative Care referral is often thought to be delayed as judged by health professionals and caregivers. However, no studies have ever examined patients’ perception of timeliness of referral. The primary objective of this study was to determine patients’ perception of the timeliness of their own referral to an outpatient palliative care clinic. We also examined the association between perceived timeliness and actual timing of referral. Methods: In this prospective survey, patients with advanced cancer were asked to rate their perceived timeliness of referral using a 5-point Likert scale ranging from much too early to much too late within 7-35 days after their first consultation visit at Supportive Care Center. They were also asked when they felt referral to Supportive Care should occur along 4 points in their disease trajectory. Actual timing of referral was assessed based on survival from the timing of completion of the survey. Results: 200 advanced cancer patients were surveyed. Median age was 64, 111 (55%) were female, and 35 (18%), 32 (16%) and 26 (13%) had gastrointestinal, lung and breast cancer, respectively. The median overall survival was 8.5 months. 144 (72%) patients perceived their referral was “just in time,” 42 (21%) felt it was “late/much too late,” and 14 (7%) felt it was much “too early/early.” 76/193 (39%) felt the referral should occur at the time of diagnosis of cancer, 32 (17%) when they start first-line chemotherapy, 46 (24%) at diagnosis of recurrent disease, 14 (7%) when there are no further treatment options, and 4 (2%) reported never. We found no significant difference in survival among patients who reported their referral was early, just in time, and late (median 9.8 vs. 8.3 vs. 9.0 months, P=0.43). Conclusions: Patients with advanced cancer were referred to our outpatient Supportive Care clinic a median of 8.5 months before death. A vast majority of patients perceived the timing of referral was appropriate, and many agreed that referral should occur early in the disease trajectory. The lack of association between perceived timeliness of referral and survival may be related to the ceiling effect and the small number of patients who felt their referral was late.
Evaluation of RAD1901, a novel investigational, selective estrogen receptor degrader (SERD), for the treatment of ER-positive (ER+) advanced breast cancer.
Authors: Bardia Aditya , Kabos Peter , Elledge Richard , Wang Dannie , Shen Jinshan , Garner Fiona , O'Neill Alison , Kaklamani Virginia G. 
Published: September 2018

1014 Background: The treatment of advanced ER+ breast cancer remains a clinical challenge with the majority of patients eventually progressing due to resistance to endocrine therapy. RAD1901 is a novel, nonsteroidal, oral SERD that has demonstrated dose dependent degradation of ER, and ER regulated genes in preclinical studies. In multiple in vivo patient derived xenograft models of breast cancer, including those harboring ESR1 mutations, RAD1901 demonstrated significant antitumor activity. Methods: In a phase-1 Study RAD1901-005 (ClinicalTrials.gov ID: NCT02338349), patients with advanced ER+ breast cancer were enrolled in dose escalation cohorts, followed by a safety expansion cohort. Key inclusion criteria include postmenopausal women aged 18 years or older, with advanced ER+, HER2- breast cancer, who have received ≤ 2 prior chemotherapy regimens in the metastatic setting and > 6 months of prior endocrine therapy. ESR1 mutation status was determined from circulating tumor DNA (ctDNA) samples. Clinical outcomes were evaluated based on RECIST v1.1 criteria. Results: As of January 25, 2017, total of 39 patients were enrolled at the 400 mg qd dose. Patients were heavily pre-treated (median lines of prior therapy = 3), with 38% and 41% having previously received fulvestrant and palbociclib/CDK4/6 inhibitor, respectively. RAD1901 was generally well-tolerated, with the most common adverse events being low grade nausea (Grade 3/4 = 0%) and dyspepsia (Grade 3/4 = 0%). ESR1 mutations, including D538G, Y537S/N/C, L536H/P/R, S436P and E380Q, were detected at baseline in 44% of patients and dynamic changes in the allele frequency of ESR1 mutations were observed in response to treatment. Confirmed partial responses were observed in patients with ESR1 mutations, and those who had previously received fulvestrant and palbociclib. Conclusions: RAD1901 has demonstrated evidence of single agent activity, with confirmed partial responses in heavily pre-treated patients with advanced ER+ breast cancer, including those with ESR1 mutations, warranting additional clinical development. Clinical trial information: NCT02338349.
Predicting sensitivity to palbociclib with early circulating tumor DNA dynamics in the PALOMA-3 trial.
Authors: O'Leary Ben , Hrebien Sarah , Morden James P , Beaney Matthew , Liu Yuan , Bartlett Cynthia Huang , Koehler Maria , Cristofanilli Massimo , Garcia-Murillas Isaac , Bliss Judith , Turner Nicholas C. 
Published: September 2018

1018 Background: Palbociclib improves progression free survival (PFS) in patients with advanced, hormone receptor positive, HER2-negative breast cancer. There are currently no biomarkers to predict sensitivity to palbociclib. We investigated if early circulating tumour DNA (ctDNA) dynamics could predict clinical outcome on palbociclib (Palbo) and fulvestrant (F) in the PALOMA-3 trial. Methods: Plasma samples were prospectively collected in PALOMA-3 for ctDNA analysis at baseline, cycle 1 day 15 (D15) and end of treatment (EOT), and were screened for PIK3CA and ESR1 mutations using digital PCR. The primary objective was to assess whether early dynamic changes in PIK3CA mutations would predict PFS in patients treated with Palbo + F. Suppression of PIK3CA ctDNA levels below an optimised cut-off at cycle 1 D15, relative to baseline levels, was termed a ‘circulating DNA ratio (CDR) response. Results: PIK3CA mutations were identified in 22.0% (100/455) of screened baseline samples with 52 of these randomised to Palbo + F and having matched D15 samples. Patients on Palbo + F with a CDR response had a median PFS of 11.2 months (95%CI 11.1 – undefined) whereas patients on Palbo + F without a CDR response had a median PFS of 4.1 months (95%CI 3.6 – 5.5) (HR for no CDR response 4.92, 95% CI 1.98 – 12.26, p = 0.0002). Overall, Palbo + F suppressed D15 PIK3CA ctDNA levels to a greater extent than placebo + F (p<0.0001). ESR1 mutations were identified in 25.6% (114/445) of screened baseline samples, 65 having matched D15 samples. ESR1 mutations showed greater ctDNA suppression than PIK3CA mutations, and were more frequently undetectable at EOT (25.8% ESR1 undetectable 8/31, v 2.6% for PIK3CA, 1/38, p=0.004). Clearance of ESR1 mutation at EOT was associated with early loss of ESR1at D15 (p = 0.027). Conclusions: Early circulating tumor DNA assessment may predict sensitivity to palbociclib and fulvestrant, and if validated by further analysis may allow treatment to be adapted prior to progression. ESR1 mutations are frequently lost after treatment with palbociclib and fulvestrant.
Health-related quality of life (HRQoL) of postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) treated with ribociclib + letrozole: Results from MONALEESA-2.
Authors: Verma Sunil , O'Shaughnessy Joyce , Burris Howard A. , Campone Mario , Alba Emilio , Chandiwana David , Manson Stephanie , Sutradhar Santosh C. , Monaco Mauricio , Janni Wolfgang 
Published: September 2018

1020 Background: In the MONALEESA-2 trial, ribociclib + letrozole significantly improved progression-free survival (PFS) and showed higher overall response rates vs letrozole alone in HR+, HER2– ABC. To place these clinical results in the context of patient experience, here we present key patient-reported outcomes (PROs) including HRQoL. Methods: 668 patients were randomized (1:1); 334 each to the ribociclib + letrozole and placebo + letrozole arms. PROs were evaluated during treatment and at progression using the EORTC QLQ-C30, QLQ-BR23, and EQ-5D-5L questionnaires. Changes from baseline in all subscales were analyzed using a linear mixed-effect model and time to 10% deterioration was compared between treatment arms using the stratified log-rank test. Results: Questionnaire compliance rates were high (≥90%). During treatment, HRQoL (global health status/QoL score) was maintained and similar in both treatment arms. At progression/end of treatment, HRQoL worsened numerically in both arms. Time to definitive 10% deterioration of HRQoL was similar between treatment groups, slightly favoring the ribociclib + letrozole arm (hazard ratio: 0.89; 95% confidence interval: 0.67–1.18). No statistically or clinically relevant differences were observed for key symptoms using EORTC QLQ-C30 including fatigue, nausea, and vomiting. There was a clinically relevant ( > 5 points) improvement in pain from baseline to post-baseline (up to Cycle 15) in the ribociclib + letrozole arm while there was only mild improvement ( < 5 points) observed in the placebo + letrozole arm. Conclusions: In addition to significantly improving PFS, ribociclib + letrozole maintains HRQoL when compared with letrozole + placebo. A numerical trend was observed favoring ribociclib + letrozole for pain reduction. Clinical trial information: NCT01958021.