bluuebunny/crossref_metadata_2025 huggingface dataset:
Ipilimumab versus placebo after complete resection of stage III melanoma: Initial efficacy and safety results from the EORTC 18071 phase III trial.
Authors: Eggermont Alexander M. , Chiarion-Sileni Vanna , Grob Jean Jacques , Dummer Reinhard , Wolchok Jedd D. , Schmidt Henrik , Hamid Omid , Robert Caroline , Ascierto Paolo Antonio , Richards Jon M. , Lebbe Celeste , Ferraresi Virginia , Smylie Michael , Weber Jeffrey S. , Maio Michele , Konto Cyril , Karra Gurunath Ravichandra , de Pril Veerle , Suciu Stefan , Testori Alessandro
Published: February 2017

LBA9008

Background: Ipilimumab (Ipi), a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 to augment antitumor immune responses, is an approved treatment for advanced melanoma. Here, we report the results of a phase III trial designed to evaluate Ipi as an adjuvant therapy for resected stage III melanoma at high risk of recurrence. Methods: In this randomized, double-blind trial, eligible patients (pts) included those ≥18 yrs of age who underwent complete resection of stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis). 951 pts were randomized (stratified by stage and region) 1:1 to receive Ipi 10 mg/kg (n=475) or placebo (Pbo, n=476) every 3 wks for 4 doses, then every 3 mos for up to 3 yrs until completion, disease recurrence, or unacceptable toxicity. The primary endpoint was recurrence-free survival (RFS), analyzed on the intent-to-treat population. 512 RFS events (recurrence or death) were needed to provide 90% power to detect an Ipi vs Pbo hazard ratio (HR) of 0.75 (2-sided α=5%). Results: Overall, 20%/44%/36% of pts had stage IIIA/IIIB/IIIC, 42% ulcerated primary, and 58% macroscopic lymph node involvement. At a median follow-up of 2.7 yrs, Ipi significantly improved RFS vs Pbo. RFS benefit was consistent across subgroups (e.g., stage IIIB or IIIC, ulcerated primary). Most common grade 3/4 immune-related adverse events (irAEs) in the Ipi and Pbo arms were gastrointestinal (15.9% vs 0.8%), hepatic (10.6% vs 0.2%), and endocrine (8.5% vs 0%). Most irAEs were managed and resolved using established algorithms. Of 471 pts who started Ipi, 245 (52%) discontinued treatment due to AEs [182 (38.6%) within 12 weeks]; 5 (1.1%) died due to drug-related AEs. Conclusions: In this phase III trial, Ipi as adjuvant therapy provided a clinically and statistically significant improvement in RFS vs Pbo for pts with stage III melanoma at high risk of recurrence. AE profile was generally consistent with that observed in advanced melanoma, although with a higher incidence of endocrinopathies. Clinical trial information: NCT00636168. EudraCT Number: 2007-001974-10. [Table: see text]
Managing comorbidities in oncology: A multisite randomized controlled trial of continuing versus discontinuing statins in the setting of life-limiting illness.
Authors: Abernethy Amy Pickar , Kutner Jean , Blatchford Patrick Jud , Ritchie Christine , Fairclough Diane , Hanson Laura , Bull Janet ,   PCRC Investigators
Published: February 2017

LBA9514

Background: For patients with life-threatening illness such as advanced cancer, optimal management of longstanding medications prescribed for comorbid illness is uncertain. Risks may outweigh benefits; e.g., benefits from HMG Co-A reductase inhibitors (“statins”) may take years to accrue and may not be relevant for a person with limited prognosis. Is it safe to discontinue statins for the patient with less than a year to live? Methods: This was a multicenter, unblinded pragmatic trial. At enrollment, participants were randomized (1:1) to discontinue or continue their statin medication. Eligible patients were adults with advanced life-limiting illness on a statin for ≥3 months for primary or secondary prevention, a life expectancy of greater than one month, and evidence of recent deterioration in performance status. Outcomes measured at baseline and at least monthly included survival, cardiovascular-related events, quality of life (QOL), symptoms, and polypharmacy. Rate of death within 60 days of randomization was the primary outcome. Results: 381 patients were enrolled (189 discontinue statins; 192 continue statins). Mean age was 74 years (SD 12); 22% were cognitively impaired; 49% had cancer as the primary diagnosis; and, 69% had used statins for >5 years. Rate of death within 60 days was not statistically different between groups (discontinue vs. continue, 23.8% vs. 20.3%, 90% CI -3.5% to 10.5%, p=0.36). The group discontinuing statins had longer median time-to-death (229 days [90% CI 186–332] vs. 190 days [90% CI 170-257]; p=0.60). Total QOL was significantly better among the group discontinuing statins (McGill QOL: 7.11 vs. 6.85, p=0.037) and there were fewer symptoms in this group (Edmonton Symptom Assessment Scale: 25.2 vs. 27.4, p=0.128). People in the discontinue statins group took significantly fewer medications (10.1 vs. 10.8, p = 0.034). Few participants in either group experienced cardiovascular events (13 vs. 11). Conclusions: In the setting of life-limiting illness such as advanced cancer, it is unlikely that harm will accrue when statins being used for primary or secondary prevention are discontinued; these patients may even benefit. Clinical trial information: NCT01415934.
Impact of breast cancer diagnosis and treatment on sexual dysfunction.
Authors: Assad Hadeel , Badhwar Gauri , Bhama Sameeksha , Vakhariya Cynthia , Goodman Judie R.
Published: February 2017

125

Background: Sexual dysfunction is a common and under acknowledged disorder in women with breast cancer. Sexual dysfunction in this scenario may be related to multiple factors: psychological distress due to diagnosis, physical decline due to treatment, change in hormonal milieu and/or poor body image. Methods: We assessed the changes in sexual activity after breast cancer diagnosis and treatment in 45 women using an anonymous questionnaire. Data was analyzed via descriptive statistics and paired sample t-test. Results: The age of women in our study ranged between 33-73 years with an average age of 51.6 years. Most of the subjects (89%) had completed chemotherapy and/or radiation therapy however 52% were still on hormonal treatment. Women who were more sexually active prior to breast cancer diagnosis were more likely to experience sexual dysfunction (p = 0.001). Overall, 45% of the women with breast cancer experienced a decline in their sexual health. A greater decline occurred after breast cancer treatment (chemotherapy and/or hormonal therapy) than after diagnosis (p < 0.05). Fifty percent had a decrease in libido and sexual arousal, 40.5% had difficulty in reaching sexual orgasm, and 29% had dyspareunia. Sexual difficulties were addressed by the treating oncologist in 3 out of the 45 women. Conclusions: The data reveals that sexual dysfunction is prevalent in breast cancer survivors. Its onset in concomitance with the diagnosis of breast cancer reflects the psychosocial impact of such a diagnosis. The further decline in sexual health after treatment emphasizes the important adverse effects of chemotherapy and hormone therapy in terms of vaginal dryness, dysparunia and sexual well-being. Despite its prevalence, sexual dysfunction is not commonly addressed in women with breast cancer. [Table: see text]
Ph IB study of LEE011 and BYL719 in combination with letrozole in ER+, HER2- breast cancer.
Authors: Munster Pamela N. , Hamilton Erika Paige , Estevez Laura G. , De Boer Richard H. , Mayer Ingrid A. , Campone Mario , Asano Shizuka , Bhansali Suraj , Zhang Vickie , Hewes Becker , Juric Dejan
Published: February 2017

143

Background: Activation of the PI3K/AKT/mTOR and cyclin D–CDK4/6–INK4–Rb pathways has been implicated in endocrine therapy resistance in pts with advanced HR+ breast cancer (BC). BYL719 (BYL), an α-isoform selective PI3K inhibitor and LEE011 (LEE), a CDK4/6 inhibitor have demonstrated clinical activity in pts with advanced HR+ BC and advanced solid tumors, respectively. In preclinical HR+ BC models, the combination of LEE, BYL, and letrozole (LET) had enhanced antitumor activity vs either agent alone. Here we report results from Arm (A)1 (LEE + LET) and A2 (BYL + LET) of the Ph Ib part of a Ph Ib/II, 3-arm study of LEE, BYL, and LET in pts with advanced ER+ BC (CLEE011X2107/NCT01872260). Methods: Postmenopausal women with advanced ER+, HER2− BC receive daily oral doses of LEE (3-wks on/1-wk off; A1) or BYL (continuous; A2), plus fixed, daily LET (2.5 mg, continuous), as part of a 28-day cycle. Primary objective: determine the MTD and/or RP2D of A1 and A2. Dose escalation is guided by a Bayesian Logistic Regression Model using the escalation with overdose control principle and real-time PK. Safety and preliminary efficacy are also assessed. Results: As of March 28, 2014, 10 pts have been treated with 600 mg LEE + LET (A1), and 7 pts with 300 mg BYL + LET (A2). One DLT was observed (A1: Grade [G]4 neutropenia; data cut-off: May 15). Common (all grade >30%) study drug-related AEs (all grade/G3–4) were: A1: neutropenia (90%/50%) and nausea (40%/0%); A2: hyperglycemia (57%/14%), decreased appetite, diarrhea, and nausea (43%/0% each). PK for LEE and BYL on Days 1 and 21, and LET on Day 1, are comparable to historic single-agent data. PK of LET at steady state is being evaluated. In A1, 6 pts had known responses: 1 PR, 2 SD, 1 NCRNPD, and 2 PD. In A2 5 pts had known responses: 2 SD, and 3 NCRNPD. Conclusions: LET plus LEE or BYL had an acceptable safety profile and preliminary signs of clinical activity have been observed. Upon determination of the MTD/RP2D in A1 and A2, enrollment into A3 (LEE + BYL + LET) will commence. The randomized Ph II part of the trial will compare LET + LEE or BYL with LET + LEE + BYL. MONALEESA-2 (CLEE011A2301/NCT01958021), a Ph III, randomized, double-blind, placebo-controlled study of LEE + LET in untreated advanced HR+ BC is currently recruiting pts. Clinical trial information: NCT01872260.
Patient-reported outcomes (PROs) from TH3RESA, a phase 3 study of trastuzumab emtansine (T-DM1) versus treatment of physician’s choice (TPC) in patients with pretreated HER2-positive advanced breast cancer.
Authors: Bartley Karen , Wildiers Hans , Kim Sung-Bae , Krop Ian E. , Kang Jennifer , Yu Ron , Leung Abraham C. F. , Trudeau Caroline , Gonzalez-Martin Antonio
Published: February 2017

153

Background: Progression-free survival and objective response rate were significantly improved with T-DM1 vs TPC in TH3RESA. The impact of treatment on quality of life is a key aspect in determining treatment value. Here we present the PRO results from the TH3RESA study. Methods: Patients were randomized 2:1 to T-DM1 (3.6 mg/kg every 21 days) or TPC. Patients were asked to complete the EORTC QLQ-C30 (a 30-item questionnaire assessing symptom bother, functioning and health status) and the EORTC QLQ-BM22 (a 22-item survey evaluating pain from bone metastases) at the start of each cycle. Data from patients with a baseline and ≥1 post-baseline assessment were included; a clinically meaningful difference was defined as ≥10 points. Time to pain progression (TPP) was assessed using the Kaplan-Meier method and Cox proportional-hazards models. Results: A greater proportion of patients in the T-DM1 arm (n=297) vs. the TPC arm (n=117) experienced a clinically meaningful improvement in global health status (57.8% [95% CI; 52.0–63.3] vs. 47.1% [95% CI; 38.4–56.4]). The most bothersome symptoms in the T-DM1 arm as measured by the EORTC QLQ-C30 were fatigue and pain. Over the first 10 T-DM1 treatment cycles, 19–30% of patients reported being impacted “quite a bit” or “very much” by fatigue, and 16–25% by pain. Nausea/vomiting and diarrhea were perceived as more tolerable, with 1–5% and 1–4% of patients reporting “quite a bit” or “very much” impact, respectively. TTP was 2.9 months in the T-DM1 arm vs 3.6 months in the TPC arm, but was not significantly different (HR 1.12 [95% CI; 0.82–1.52], p = 0.495). Mean baseline EORTC QLQ-BM22 pain scores were similar in the T-DM1 (n = 306) and TPC arms (n = 130); (25.4 ± 23.8 [SD]) and (27.3 ± 24.4), respectively. There were no clinically meaningful changes in pain levels from baseline over time in either arm. Conclusions: For patients on T-DM1, the most impactful symptoms were fatigue and pain, while the least bothersome were diarrhea and nausea/vomiting; distribution of severity of impact was relatively stable over the first 10 cycles of treatment. TPP was similar between the T-DM1 and TPC arms. Clinical trial information: NCT01419197.
Qatar experience of standard risk breast cancer screening program (BCSP).
Authors: Bujassoum Salha M. , Alassam Reena , Bugrein Hekmat
Published: February 2017

18

Background: Qatar has one of the highest age-adjusted breast cancer incidences in the Arab world. Although this is much lower than the incidence in the West. Breast-cancer incidence in Qatar was 45 per 100,000 in 2003 to 2007.These higher incidence rates in Qatar are mainly due to the growing population. The prevalent age group, for Qatari and non-Qatari patients, was age 40 to 50. This suggests that the age-specific incidence of breast cancer in Qatari women is unlike the pattern usually seen in Western nations where median age at diagnosis is 61 years, moreover the diagnosis is often at advanced stages of breast cancer. These factors led to establishment the first hospital based (BCSP) in Qatar. It uses a distributed model of mammography service. The program launched 2008, accepts eligible asymptomatic women at ages 40 to 69. Methods: Retrospective study was done during the period from April 2008 to December 2013. Our aim is to describe our experience of (BCSP) in Qatar and to monitor performance indicators. Our (BCSP) includes an office call and recall as well as triple assessment. We also discuss positive cases in multidisciplinary meeting. Results: Total number of screened women was 4,264 with an increasing participation, year by year. Out of these, Qatari patient’s accounts for 1,145, and non Qatari for 3,119. The age group of cases was (43 to 51). Total breast biopsies were 82, of which 45 were positive of breast carcinomas, (37) invasive ductal carcinoma, (8) noninvasive ductal carcinoma. The invasive cancer detection rate was 8.2 %. The positive predictive value (PPV) was 46%. Sensitivity value has improved from 51% in 2008 to 70% in 2012 as well as specificity value that has increased from 77% in 2008 to 83% in 2012. Conclusions: Public acceptance of (BCSP) in Qatar gradually increased and detection rates are higher than western countries. We’re detecting biologically aggressive tumors at younger age groups. We’ve a unique population and we need to utilize our data and evidence based medicine to guide policy makers and women to make the correct decision towards (BCSP).
A program evaluation of best practice methods to assess integrated health needs for breast cancer survivors.
Authors: Gilmore Katherine Ramsey , Damani Shamsha , King Rachel M , Nelson Bonnie , Austin Allica , Scroggs Sally , Bevers Therese Bartholomew , Zandstra Frances Ann
Published: February 2017

111

Background: A fundamental tenet of survivorship care is to identify and deliver a wide range of supportive care services. Survivors rely on clinicians to provide integrated care personalized to their own supportive care needs. Yet there is lack of evidence demonstrating which method is “best practice” when assessing survivor’s needs. The aim of our Plan-Do-Study-Act quality improvement project was to determine the best method to identify survivors’ supportive care needs and coordinate services. Methods: We used the appointment list of the Breast Survivorship Clinic to identify 114 adult survivors seen for their initial survivorship visit between January-March 2014. Survivors were asked to complete a questionnaire assessing their needs related to: 1) energy-balance, 2) complementary medicine, 3) lymphedema, 4) psychosocial concerns, 5) sexual health, and 6) tobacco use. Survivors were randomly assigned into 3 groups to identify the best method to assess their health care needs: 1) Mail, 2) Secure Electronic Messaging, and 3) Navigation Visit with Health Educator (HE). Questionnaires for the mail and electronic messaging groups were distributed before being seen in the clinic. Navigation participants completed the questionnaire during the visit with HE. Descriptive statistics were used to describe and compare group characteristics. Results: A total of 114 patients were randomized to complete the assessment by either mail (N=28), secured electronic message (N=50), or during the navigation visit (N=36). The in-person, navigation visit had the highest completion rate (78%) compared to secured message (22%), and mail (7%). An overwhelming majority of survivors’ in the navigation group (93%) indicated they had needs in in at least one of the 6 domains. The top two needs across all groups were nutrition and physical activity. Conclusions: This evaluation suggests the use of a health navigator to guide the survivor through the needs assessment was the most successful way to assess needs of long-term breast cancer survivors. Enhanced navigation during a cancer survivor’s visit can be used to tailor integrative health services, which can improve their well-being and mental health outcomes.
Multidisciplinary breast clinic: Impact on patient satisfaction, timeliness, and guideline concordant care.
Authors: Gomez Caitlin Laurel , Dawson Nicole Ann , Dvorak Robyn Lynn , Foster Nova , Hoyt Anne , Hurvitz Sara A. , Kusske Amy , Tseng Charles Y. , McCloskey Susan Ann
Published: February 2017

124

Background: After recent implementation of a multidisciplinary breast clinic (MDC) for newly diagnosed women at our institution, we sought to examine the impact of MDC on patient satisfaction, timeliness and guideline concordant care. Methods: Women with newly diagnosed breast cancer at our institution are referred to MDC where they are seen by a team of breast specialists for initial consultation. The MDC model is further facilitated by a patient navigator/coordinator who serves as a single point of contact across disciplines and through the continuum of care. We deployed patient satisfaction surveys querying helpfulness of the care coordinator and satisfaction with seeing breast cancer specialty physicians together in one visit. We further retrospectively analyzed timeliness of care and guideline concordant care since MDC implementation. Results: Patient satisfaction survey response rate was 42% (n=133).On a scale of 1 (very poor) – 5 (excellent), 93% of respondents rated helpfulness of care coordinator as excellent and seeing specialty physicians together in one visit as excellent. 99% of respondents rated these factors as either excellent (5) or good (4). Regarding timeliness, among 202 women with newly diagnosed, non-metastatic breast cancer seen in MDC between June 2012 and April 2014, mean time from neoadjuvant chemotherapy to surgery was 43.1 days (range 26-78 days), from surgery to adjuvant radiation was 39.2 days (range 22-79 days), from surgery to adjuvant chemotherapy was 40.6 days (range 19-89 days), and from adjuvant chemotherapy to radiation was 34.9 days (range 13-67 days). All timeliness metrics well exceeded established national standards of 60-90 days. Regarding guideline concordant care, 94% and 90% respectively received indicated radiation therapy and chemotherapy in accordance with National Comprehensive Cancer Network (NCCN) Guidelines. Those not receiving guideline concordant care either declined, were of advanced age, or had prohibitive co-morbidities. Conclusions: The MDC model, which emphasizes care coordination via a team approach and patient navigation, is associated with excellent patient satisfaction and timely, guideline concordant breast cancer care.
Individual attributions of living longer with HER2+ metastatic breast cancer: Findings from a community web-based survey.
Authors: Mayer Musa , Sussman Matthew , Masaquel Anthony , Kamath Tripthi , Lai Catherine , Tripathy Debu , Hurvitz Sara A. , Menzin Joseph
Published: February 2017

197

Background: Advances in targeted therapy have led to an increase in the median overall survival in patients with HER2+ metastatic breast cancer (MBC). However, patient attributions related to living longer have not been studied. Methods: A one-time, web-based survey was administered through multiple US-based breast cancer organizations. The inclusion criteria were being female, age 18+, having HER2+ MBC, and living in the US. The surveys included health related quality of life (HRQL), symptom burden, activities of daily living, satisfaction with medical care, work productivity, and attributes of living longer. To assess beliefs about length of survival with HER2+ MBC, participants were asked to rate the importance of 16 items. Descriptive results were stratified by time since metastatic diagnosis and HRQL. Results: Of 560 attempted surveys, 365 (65%) participants met inclusion criteria. Mean (SD) age was 53.6 (10.5) years, 93% were white, and 27% reported having participated in a clinical trial. 59% of respondents reported living ≥4 years since HER2+ MBC diagnosis. Common reasons patients gave for living longer included: choosing the right doctor/medical team (91%), having a positive outlook on life (79%), and learning about the disease or treatments (79%). Women with <4 years since HER2+ MBC diagnosis were more likely to report having a positive outlook on life (85% vs 76%), using complementary and alternative medicine (45% vs 36%) and exercising regularly (74% vs 66%) compared with those having ≥4 years since diagnosis. Women reporting a better compared with a poorer HRQL reported more frequent regular exercise (73% vs 49%) and more often had a positive outlook on life (86% vs 64%). Conclusions: To our knowledge, this is the first study of women with HER2+ MBC and their attributions about length of survival. Having the right medical team, remaining positive, and being educated about the disease and its treatments were most important to participants. Women reporting better quality of life were more likely to report multiple attributions of living longer. HRQL and patient perceptions about their survival are important factors that should be considered in providing patient-centered care.
Daily rounds on inpatient oncology floor by inpatient hospitalist oncologist and reduced length of stay.
Authors: Mekan Sabeen Fatima , Loen Dan , Raptis George , Budman Daniel R.
Published: February 2017

228

Background: Hospitalist services have expanded recently resulting in improved patient care and reduced length of stay compared with traditional inpatient services. Methods: We implemented an inpatient oncology hospitalist service with consistent daily rounding by the same team on all patients on the oncology floor in July 2012 and compared the impact on inpatient length of stay (LOS), inpatient mortality, cost saving, 30 day readmission rate and patient satisfaction scores before and after. Data was collected from hospital administration from patient medical and billing records. Results: The changes had an immediate effect on LOS which reduced from 7.30 days to 6.38 days over the next 6 months and further trended down to 6.20 over the next 11 months. Total number of discharges increased from 839 from Jan-Jun 2012 to 947 in Jan-Jun 2013. Decrease in LOS occurred in almost all groups including patients with and without cancer. However, the greatest reduction occurred in patients who were admitted with primary diagnosis related to complications of their cancer from 11.2 days to 9.0 days from Jan-Jun 2012 to Jan-Jun 2013. Inpatient mortality decreased from 37 to 30 from Jan-Jun 2012 to Jan-Jun 2013 and discharges to hospice increased from 42 to 65 patients. The 30 day readmission rate increased slightly from 196 to 222 patients. The most common admission diagnoses remained relatively constant. The payer mix of the patients, administrative structure and staffing on the floor remained unchanged during this time period. Patient satisfaction measured by the overall Press-Ganey scores remained unchanged. Conclusions: Daily consistent rounding of inpatient hospitalist service had a significant positive impact on all patients especially patients admitted with oncologic diagnoses. It also resulted in decrease in inpatient mortality and increased the number of discharges to hospice without significant increase in readmission rate.
Patient-reported outcomes (PROs) from the systemic therapies for HER2-positive metastatic breast cancer (MBC) registry study (SystHERs): Eliciting the patient experience.
Authors: Hurvitz Sara A. , Jahanzeb Mohammad , Kaufman Peter , Mason Ginny , Mayer Musa , Rugo Hope S. , Tripathy Debu , Ogale Sarika , Masaquel Anthony , Yoo Bongin , Beattie Mary , Cobleigh Melody A.
Published: February 2017

286

Background: Patients with HER2-positive MBC are, on average, living longer. Data are limited on patient-reported quality of life (QoL) and economic burden during these extended survival periods. In accordance with guidelines for comparative effectiveness research in oncology (Basch et al, 2012), SystHERs, initiated in 2012, includes PROs to capture the patient experience. Here we report baseline (at enrollment) PRO results from SystHERs. Methods: SystHERs is a US-based prospective observational cohort study that aims to enroll 1000 patients with HER2-positive MBC within 6 months of metastatic diagnosis. Patients will be followed for 5–8 years.PROs, including QoL, economic burden, and symptoms related to neuropathy, alopecia, and cognition, are collected at baseline and ~90-day intervals during clinic visits, including after disease progression. Results: As of Feb 17, 2014, 319 patients were enrolled, and baseline data from 306 eligible patients are reported. Median time to enrollment since MBC diagnosis was 2.4 months. At least 1 PRO item was completed by 90% of eligible patients. Scale reference ranges (higher scores indicate better status) and median scores at baseline were: overall HRQoL (0–100)=80.0; FACT-B Trial Outcome Index (0–96)=58.0, and the Rotterdam Activities of Daily Living Scale (0–100)=85.7. One hundred patients (40.3%) were employed. These patients reported on average 36% work time missed (absenteeism) and 30% decreased on-the-job effectiveness (presenteeism) due to MBC. Patients reported a median out-of-pocket MBC-related expenditure of $735 in the past 3 months (range $0–11,700). Of this, the median deductible and copay-related cost was $350. Conclusions: To our knowledge, this is the only HER2-positive MBC patient registry that includes comprehensive PROs to supplement clinical data. To date, participation in PROs is high at baseline (90%).QoL and economic burden were consistent with other studies (Cortés et al, 2013; Zafar et al, 2013). Baseline results for ~500 patients are expected by the time of the congress presentation and will include data on symptoms related to neuropathy, alopecia, and cognition. Clinical trial information: NCT01615068.
Point-of-care clinical decision support for cancer symptom management: Results of a group randomized trial.
Authors: Cooley Mary E. , Blonquist Traci , Catalano Paul , Lobach David , Braun Ilana , Halpenny Barbara , McCorkle Ruth , Rabin Michael , Johns Ellis , Finn Kathleen , Abrahm Janet , Berry Donna Lynn
Published: February 2017

1

Background: Integration of palliative care into oncology is recommended for quality care. Clinicians may benefit from assistance in assessing and managing multiple symptoms. Palliative care clinicians have the expertise but may not be available or are not consulted early in the course of a patient’s disease. Clinical decision support (CDS) offers an innovative way to deliver symptom management and trigger palliative care referrals at the point-of-care. Methods: Twenty clinicians and their patients were randomized to usual care (UC) or CDS using the symptom assessment and management intervention (SAMI), which provided tailored suggestions for pain, fatigue, depression, anxiety and/or dyspnea. One-hundred seventy-nine patients completed a Web-based symptom assessment prior to each visit for 6 months. A tailored report provided a longitudinal symptom report and suggestions for management were provided to clinicians in the SAMI arm prior to the visit. Standardized questionnaires were administered to patients at baseline, 2, 4 and 6 months later to measure communication about symptoms and health-related quality of life (HR-QOL). The treatment outcome index (TOI) was the primary outcome for HR-QOL. Management of the target symptoms was assessed through chart review. Linear mixed models and logistic regression were used for analyses. Results: Patient characteristics were: mean age of 63 years, 58% female, 88% white, and 32% had < HS education. No differences were noted in communication between patients and their clinicians. Significant differences were noted in physical well-being (p = 0.007, 0.08 adjusted for baseline) and a clinically significant difference in the TOI (62 vs. 68) at 4 months in SAMI as compared to UC. The odds of managing depression (1.6, 90% CI, 1.0-2.5), anxiety (1.7, 90% CI, 1.0-3.0) and fatigue (1.6, 90% CI, 1.1-2.5) were higher in SAMI as compared to UC. The odds of palliative care consults for pain (3.2, 90% CI, 0.7-13.4) appear to be higher in SAMI as compared to UC. Conclusions: Enhanced HR-QOL was noted among patients in the SAMI arm at 4 months. SAMI increased management of depression, fatigue and anxiety and appeared to increase palliative care consults for pain. Clinical trial information: NCT00852462.
Which patients experience improved quality of life (QOL) and mood from early palliative care (PC)?
Authors: Nipp Ryan David , Greer Joseph A. , Traeger Lara , Gallagher Emily R. , Park Elyse R. , Jackson Vicki A. , Pirl William F. , Temel Jennifer S.
Published: February 2017

16

Background: Prior research has demonstrated improved patient outcomes with early PC integrated with standard oncology care (SC), but it is not clear if these associations exist in all patient demographic groups. This study examined whether early integrated PC was associated with improvements in QOL and mood in different demographic groups. Methods: This is a secondary analysis of data from a randomized controlled trial of 151 patients with newly diagnosed metastatic non-small-cell lung cancer presenting to an outpatient cancer center from June 2006 to July 2009. Patients received either early PC integrated with SC or SC alone. QOL (Functional Assessment of Cancer Therapy–Lung [FACT-L] and Trial Outcome Index [TOI]) and mood (Hospital Anxiety and Depression Scale depression subscale [HADS-D] and Patient Health Questionnaire 9 [PHQ-9], scored categorically) were assessed at baseline and 12 weeks. Data were analyzed to assess relationships between outcome variables and patient demographic characteristics (age and gender). Results: At baseline, QOL and mood outcomes did not differ significantly between treatment groups for age or gender. At 12 weeks, the PC group showed better QOL and lower rates of depressive symptoms for males and those < age 65. In comparison, QOL and mood did not differ significantly between study groups for females and those ≥ age 65. Conclusions: Males and patients < age 65 experienced improved QOL and mood with early, integrated PC. However, these outcomes did not differ significantly between treatment groups for patients ≥ age 65 or for females. Further research should confirm these findings and tailor interventions to meet the unique needs of all patients with cancer. [Table: see text]
Bone health in prostate cancer patients: A survivorship issue requiring intervention.
Authors: Dawson George A. , Greener Anne , Reyes-Dawson Dalila , Malhotra Sheetal , Weinbrom Sarah , Jain Anudh , Reddy Sadhana , Kelly Maria D.
Published: February 2017

247

Background: In general, men are not routinely screened for bone health. Prostate cancer patients are at an increased risk because of treatment with androgen deprivation therapy (ADT). Unlike other patients diagnosed with a malignancy, they may survive a long time. Some risk factors include inadequate calcium, vitamin D deficiency, tobacco use and alcohol abuse. We implemented a pre-ADT program to mitigate the effects of ADT on bone health. This study evaluates the pre-existing risk factors and bone health by baseline DEXA scans pre-ADT initiation. Methods: We completed a chart review of 182 veterans referred to Radiation Oncology for curative treatment of prostate cancer from 2009 to 2013. Of those, 160 patients underwent baseline DEXA scans. Clinical variables analyzed were demographics, tobacco and alcohol use, vitamin D levels, incidence of AODM (adult onset diabetes mellitus), and calcium or vitamin D intervention. Descriptive statistics and bivariate analysis including Chi Square tests and odds ratios were carried out. Results: The mean age of the study participants was 66.6 years (range 47-82.8 years). Baseline DEXA scans were abnormal in 63% of patients, showing osteoporosis and/or osteopenia. Vitamin D levels were abnormal in 61% of patients- 26% of whom had normal DEXA scans. Twenty percent had a history of alcohol abuse, and 56% used tobacco; 33% had AODM. Smokers with an abnormal Vitamin D level were at increased risk of bone disease as compared to non smokers (OR 3.23, 95% CI 1.35-7.69 p<0.01). Variables significantly impacting bone health were age (OR 1.087, p=0.012, 95% CI 1.018-1.161) and Tobacco use (OR 0.424, p=0.045, 95% CI 0.183-0.980). Almost 90% of the patients in this study had intermediate risk prostate cancer with an expected cancer specific survival of 85 to 90% at 5 to 10 years. Conclusions: Pre-ADT screening confirms the risk of underlying bone disease in this veteran population with an expectation of long term survival. Guidelines for treatment and prevention of bone disease should be implemented in all patients over age of 50. Particular attention should be paid to patients who underwent ADT. This can affect the quality of life in this group of cancer survivors.
Impact of a nurse practitioner-staffed, symptom-management clinic on emergency department utilization in a large community oncology cancer institute.
Authors: Sivendran Shanthi , Holliday Rachel , De la Torre Kristen , Newport Kristina Braine
Published: February 2017

58

Background: Emergency department (ED) utilization among oncology patients is a source of patient distress as well as a financial burden to the health care system. Effective outpatient symptom management can potentially reduce ED utilization. In this analysis, we review ED utilization prior to and post the institution of a nurse practitioner staffed symptom management clinic in a large community oncology practice. Methods: In April 2014 a symptom management clinic staffed by a nurse practitioner five days a week was established at our outpatient cancer institute to increase patient access to acute symptom management. ED utilization 6 months prior to and post starting this clinic was measured. Only patients who received chemotherapy within 30 days of an ED visit were included in this analysis. Results: Between October 2013 and September 2014, a total of 420 visits to the ED were documented. A total of 196 visits occurred in the 6 months prior to establishing the clinic. There was an increase in visits to 224 after instituting the clinic. The median number of monthly visits was 34.5 (range 24-38) prior to the clinic and increased to 38 (range 30-43) after establishing the clinic. Conclusions: In our practice, a nurse practitioner led symptom management clinic did not reduce ED utilization in patients receiving chemotherapy. Based on published studies, other factors may need to be incorporated into our cancer institute to effectively reduce ED utilization. These include standardizing symptom assessment and management, patient and caregiver education on how to effectively manage symptoms at home, and improved coordination with supportive services.
Facilitators and barriers to advance care planning in oncology.
Authors: Paladino Joanna , Bernacki Rachelle , Hutchings Mathilde , Billings J. Andrew , Block Susan
Published: February 2017

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Background: For seriously ill patients to plan for the end of life, they need to discuss with their clinicians their prognosis, values, and goals, yet such conversations often begin very late in the course of illness. To promote early advance care planning (ACP) in oncology, facilitators and barriers to these conversations need to be identified. Objectives: 1. To determine the effectiveness of “triggers” that remind oncologists to complete ACP discussions with outpatients whom they expect might die within a year. 2. To prospectively evaluate clinician-identified barriers to these conversations. Methods: A cluster-randomized controlled trial. The intervention includes: clinician identification of patients at high risk of death within a year; 2½ hour training program on the use of the Serious Illness Conversation Guide; an email trigger/reminder, immediately before an outpatient visit, for the oncologist to conduct an ACP discussion using the Conversation Guide; clinician reports of why they deferred such conversations. Results: Eighty-eight enrolled oncology clinicians (MDs, NPs, PAs) screened 15,576 patients and identified 1,743 for whom they would not be surprised about death within a year. To date, 332 patients have consented to enrollment; 104 patients and 40 clinicians entered the intervention arm; 124 subsequent visits were triggered, resulting in 62 completed conversations. 79% of the conversations occurred after 1 trigger; 92% by the second trigger. Of the 62 triggered visits that did not result in an immediate conversation, clinicians identified the following reasons: 26% not enough time; 20% clinician attitudes about the impact and timing of such conversations (i.e., they take away hope, patient not sick enough); 46% immediate patient issues making conversation inappropriate (i.e., patient acutely ill, anxious, depressed, or not ready); and 8% “other.” Conclusions: An email trigger in the outpatient oncology clinic is highly effective in promoting ACP conversations for trained clinicians. The majority of clinician-identified barriers to such discussions reflect beliefs about the impact and timing of the discussion and concerns about the patient’s immediate condition; time constraints only account for about a quarter of delays. Clinical trial information: NCT01786811.
Helping cancer-family caregivers with end-of-life home symptom management: Initial evaluation of an automated symptom monitoring and coaching system.
Authors: Mooney Kathi , Berry Patricia , Wong Bob , Donaldson Gary
Published: February 2017

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Background: Family caregivers face the task of providing end of life care (EOL) in the home setting and need effective caregiving support. Although not previously tested in EOL care, automated symptom monitoring has shown promise for cancer patients on active treatment. This study tests an automated monitoring and coaching system for family caregivers during home hospice. Methods: Family Caregivers (FC) of hospice cancer patients (PT) (N=243 dyads) were monitored daily using an automated telephone symptom monitoring system, and randomly assigned to receive the symptom care intervention (SC) (N=119) or usual care (UC) (N=124). All FCs called the monitoring system daily, reporting by proxy, past 24 hour presence, severity and FC distress on 11 common PT symptoms (0–10 scale). In addition, FCs reported their own fatigue, sleep, mood and anxiety severity (0-10 scale). The SC intervention FCs received automated tailored symptom care coaching based on reported patterns; in addition symptoms moderate or greater generated alerts to their hospice nurse. Results: Most FCs and PTs were White (95; 94%), 66% of FCs and 48% of PTs were female with the Mean age for FCs 60 and 73 for PTs. Most frequent PT symptoms were fatigue (70%), pain (64%), poor appetite (54%), anxiety (39%), and change in thinking (38%). PT symptom severity levels were highly related to FC distress. Preliminary analyses indicates that FC vitality (FC combined symptoms) improved more in the SC group (p=.003, mixed effects model). Furthermore PT symptom severity, categorized as Mild (<=3), Moderate (4-6), or Severe (>=7), provided strong preliminary evidence of SC intervention benefit in each of the first four weeks in hospice care and overall (p=.003). Rapid onset of the SC benefit was suggested by Kaplan-Meier analysis of time to first all-zero symptom profile (p=.06 log-rank). The benefit of the SC intervention continued throughout the hospice stay until the last several days of life when there was no difference with UC. Conclusions: This is the first reported evaluation of automated symptom monitoring in home EOL care and provides strong preliminary evidence of benefit for cancer family caregivers and patients. Clinical trial information: NCT02112461.
Quantification of HER2 from gastroesophageal cancer (GEC) FFPE tissue by mass spectrometry (MS).
Authors: Hembrough Todd A. , Henderson Les , Rambo Brittany , Liao Wei-Li , Thyparambil Sheeno , Bangali Kathleen , Uzzell Jamar , Darfler Marlene , Krizman David , Xu Peng , Xiao Shu-Yuan , Zhao Lei , Burrows Jon , Catenacci Daniel Virgil Thomas
Published: February 2017

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Background: Trastuzumab had a survival benefit in ‘HER2 positive’ GEC, determined by IHC/FISH. These companion diagnostics have limitations. IHC is semi-quantitative, subjective, and sensitive to antigen instability in FFPE; FISH is laborious, expensive, and subjective. Gene amplification may not correlate to protein expression. Moreover these are low throughput assays. There is increased recognition of profound interpatient molecular heterogeneity with several putative biomarkers, and only scarce tissue to assess for each one. We sought to evaluate our MS platform on GEC FFPE tissues for HER2 status compared to IHC/FISH. We also applied the “GEC-plex” of 11 other potentially predictive/prognostic markers for GEC. Methods: We utilized trypsin digestion mapping of rHER2 to identify unique peptides for SRM development. Stable isotope-labeled peptides were synthesized as internal standards, and standard curves were generated in a complex eukaryotic matrix (PC3 cells) to determine LOD, LLOQ, accuracy, precision and linearity of the assays. The assay was run on 17 GEC cell lines, in parallel with FISH/IHC, and expression thresholds were established for HER2+/HER2-; the sensitivity/specificity of the established cutoffs were then tested prospectively in FFPE GEC tissues on 10uM FFPE LCM slides (n=121). HER2 stability from FFPE sections was assessed by assaying 33 freshly cut FFPE samples; the adjacent sections were processed one year later. Results: The HER2 peptide chosen (ELVSEFSR) had a LOD of 100 amol and CV<20%. HER2 MS on GEC cell lines revealed concordance with FISH (HER2:CEP17) ratio (R2=0.96). The analysis suggested HER2 expression > 750 amol/ug was indicative of HER2 amplification. The assay was stable in archival FFPE sections (R2=0.76). For GEC FFPE cases, ‘any’ HER2 expression was seen in 69.4% of cases; 8.2% showed HER2 > 750 amol (10/121) - all were HER2 amplified. No cases <550 amol/ug were HER2 amplified. IHC/FISH results for cases with 550-750 amol/ug demonstrated a heterogeneous ‘equivocal’ zone, not unlike ‘IHC 2+’, which may require FISH confirmatory testing. Conclusions: ‘GEC-plex’ has a quantitative, sensitive, and specific HER2 assay that can be multiplexed along with other GEC biomarkers.
Arginine deiminase: A novel radiosensitizer in pancreatic cancer in vitro and in vivo.
Authors: Deorukhkar Amit , Diep Nga , Chatterjee Dev , Diagaradjane Parmeswaran , Bomalaski John S. , Krishnan Sunil
Published: February 2017

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Background: The benefits of chemoradiation therapy in patients with locally advanced pancreatic cancer (LAPC) are limited due to the inherent radioresistance of pancreatic cancer (PC) and high systemic toxicity of current radiosensitizers (e.g., gemcitabine). Hence, the search for newer radiosensitizers with unique anticancer properties continues. Single amino acid arginine starvation is a new promising therapeutic approach for solid tumors (e.g., PC), that are auxotrophic for non-essential amino acids. Arginine degrading enzyme, arginine deiminase (ADI), deprives cells of arginine and thereby exerts its anti-proliferative effects, especially in cancer cells deficient in enzyme argininosuccinate synthase (ASS1). Here we evaluate the effects of ADI-polyethylene glycol formulation (ADI-PEG20) as a radiosensitizer in PC. Methods: The toxicity of ADI-PEG20 in vitro was evaluated using XTT. Effect of ADI-PEG20 as radiosensitizer was determined by clonogenic cell survival. For in vivo, mice with PC tumor xenografts (Panc1), randomized into four groups, were treated with vehicle (PBS), ADI-PEG20 (5 IU/mouse; twice weekly), radiation (IR; 2 Gy × 5 times), and ADI-PEG20 with IR. Tumors were measured following treatment and the tumor re-growth delay time for each group was calculated. Immunohistochemical analysis of Ki-67 and VEGF was done on tumor tissues (paraffin sections) by routine immunofluorescence. Results: ADI-PEG20 selectively sensitized ASS1 deficient PC cells to IR at low, non-toxic concentrations (0.04 and 0.08 μg/mL for 72 h; DER at 10% SF for Panc1 was 1.39 and 1.52; for Miapaca-2, 1.09 and 1.25 respectively), but not ASS1 positive cells (L3.6pl). In vivo, ADI-PEG20 profoundly sensitized PC cells to IR. IR treatment alone delayed the tumor doubling time (7.6 ± 1.7 days compared to the non-treated controls); however, combining ADI-PEG20 with IR delayed the tumor growth by an additional 10 ± 1.3 days (p<0.05). Immunohistochemical analysis of tumor tissues suggested that ADI-PEG20 with IR down-regulates the expression of Ki-67 and VEGF. Conclusions: ADI-PEG20 potently radiosensitizes PC cells in vitro and in vivo. The detailed molecular mechanism of this radiosensitization warrants further investigations.
Patient-reported satisfaction with symptom control during lanreotide autogel/depot (LAN) treatment for carcinoid syndrome (CS) in gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients: Symnet, a large multinational, cross-sectional, observational study.
Authors: Ruszniewski Philippe B. , Caplin Martyn E , Valle Juan W. , Lombard Bohas Catherine , Maisonobe Pascal , Atlan Philippe ,   SYMNET Study Group
Published: February 2017

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Background: Somatostatin analogs are used to reduce the incidence and severity of symptoms of CS in GEP-NET patients. How this impacts on patients’ satisfaction needs further investigation. Methods: At routine clinic visit, GEP-NET patients with CS-related diarrhea and > 3 months LAN treatment completed questionnaires (including Likert scales) on satisfaction with diarrhea control (primary endpoint) and other symptoms following treatment. Investigators also recorded, based on chart reviews, demographic parameters, disease history, diarrhea characteristics and symptom changes for analysis of predictive factors for satisfaction. NCT01234168. Results: Of the study population (n=273), 56% were male, 57% were aged >60 yrs, mean time since diagnosis was 4.4 yrs, 66% had small bowel primary tumor, and 80% had liver metastases. Within the prior 3 mo, 66% had surgery and 23% other anti-tumor therapy. Mean LAN treatment duration was 21.7 mo and median dose on visit day 120 mg/mo. The study showed most patients (76%) were “completely” or “rather satisfied” with their diarrhea control. Similar satisfaction (73%) with flushing control was also reported. Most patients (79%) reported an overall improvement in their diarrhea with LAN treatment, and more had no or mild impact on daily activities during treatment (75%) than before (33%). Investigators identified a clinically relevant decrease in daily stool frequency from treatment initiation to current visit (median of 4 to 2). Furthermore, statistically significant decreases (McNemar paired tests, p<0.001) were seen in no. of patients with urgency (73-41%), leakage (21-9%), and associated pain (37-14%). Baseline stool leakage and localization of primary outside small bowel were factors associated with satisfaction with diarrhea control. Conclusions: Patient-reported information indicates that LAN-treated GEP-NET patients achieve good and sustained control of CS symptoms. Analyses of predictive factors could help identify patients who may benefit the most of LAN. Clinical trial information: NCT01234168.