bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of melanoma brain metastases treated with stereotactic radiosurgery with and without concurrent immune checkpoint therapy.
Authors: Yang Jessica , Dercle Laurent , Yaeh Andrew M. , Yeh Randy , Manson Daniel K. , Saad Shumaila , Jeffrey Bruce N. , Sisti Michael B. , McKhann Guy M. , Wang Tony J. C. , Schwartz Lawrence H. , Carvajal Richard D.
Published: September 2018

e21026

Background: Evidence supports a synergistic effect between immunotherapy and radiotherapy. In this single-institution study, we compared outcomes of patients (pts) with melanoma brain metastases (BMs) who received Gamma Knife Radiosurgery (GKRS) with and without concurrent immune checkpoint blockade (ICB). Methods: Using an IRB-approved protocol, we identified pts with melanoma BMs who received GKRS from 5/2000 to 8/2016. Treatment was deemed concurrent if patients had GKRS within 4 weeks of ICB. Irradiated lesion control, tumor growth rate (TGR; percent change in product diameters per month), distant brain control, overall response rate (ORR) by modified WHO criteria, best response, and overall survival (OS) were compared. Results: 28 pts were identified: 17 (34 BMs total) received GKRS alone; 11 (23 BMs total) received concurrent GKRS/ICB. ICB included: ipilimumab (n = 3), anti-programmed death-1 (anti-PD-1) therapy (n = 4), and combined ipilimumab + nivolumab (n = 4). In comparing baseline characteristics between the GKRS alone and GKRS/ICB groups: median age was 65 v. 59 years, proportion of males was 53% v. 73%, 41% v. 45% had prior neurosurgery, and median number of prior systemic therapies was 1 v. 0. There was no difference in irradiated lesion control (6-month control rate 86% v. 96%; n = 57; p = 0.65), median TGR (-14% [range -100% to +61%] v. -20% [range -71% to 0%]; n = 42 lesions, p = 0.38), or distant brain control (6-month control rate 68% v. 60%; p = 0.51; median follow-up 8.6 months v. 8.0 months) with GKRS/ICB v. GKRS alone. The ORR with GKRS alone v. GKRS/ICB was 61% v. 47% (p = 0.33), and the median maximum reduction in BM bidimensional measurement was -69% v. -45% (p = 0.43). Median OS from the date of GKRS was not reached for the GKRS/ICB group and was 16.6 months for the GKRS alone group (p = 0.03). Conclusions: There was no difference in local lesion control, TGR, or distant brain control with concurrent GKRS/ICB compared to GKRS alone, but the study was limited by small patient numbers and biased by closer follow-up in the GKRS/ICB group. OS was longer with concurrent ICB, likely reflecting the survival improvement with immune checkpoint inhibitors.
Frequency and outcomes of melanoma subtypes in a diverse population: The Los Angeles County – University of Southern California (LAC-USC) Medical Center experience.
Authors: In Gino Kim , Yang Dongyun , Thomas Jacob Stephen , Pham Anthony , Basu Arnab , Mehta Arjun Ajay , Miller Kimberly Ann , Cockburn Myles , Hu James
Published: September 2018

e21063

Background: Melanoma is a biologically heterogeneous disease that varies by ethnicity and histology. While superficial spreading (SSM) histology is the most common subtype in non-Hispanic whites (NHW), acral lentiginous (ALM) and other subtypes occur more frequently in Hispanics, Asians and African Americans. There are no known risk factors for ALM, and further investigation is warranted. Methods: We retrospectively reviewed a database of melanoma patients diagnosed between 2001-2016 at LAC-USC. Overall survival (OS) was estimated using Kaplan-Meier methodology, and comparisons performed using log-rank testing. Fisher’s exact test was used to evaluate associations between relevant clinicopathological variables. A p-value < 0.05 was considered statistically significant. Results: Among 272 melanoma patients, there were 140 Hispanics (51.5%), 105 NHW (38.6%), 14 Asians, and 4 African Americans. The most frequent histology among Hispanics was ALM (30.7%), while SSM was the most frequent among NHW (33.3%). BRAF V600 mutations were found in 34.5% (10/29) and 58.8% (10/17) of Hispanics and NHW, respectively. A total of 52 patients with ALM were identified, including 43 Hispanics (82.7%). There was a significant association between no prior history of non-melanoma skin cancer (NMSC) and ALM (p < .0001). Median Breslow thickness for ALM was 4.2 mm, and 32.7% were ulcerated. The rate of BRAF V600 mutations among 13 ALM patients tested was 0%. NRAS mutations were found in 3 ALM patients; KIT amplification/mutations were found in 2 ALM patients. Conclusions: We identified a population enriched for Hispanic patients with ALM. We found an association between no prior NMSC and ALM, suggesting that UV exposure is not a causative risk factor. BRAF mutations are less common amongst Hispanics, and nearly absent in ALM. Survival differences were not statistically significant, but cannot be ruled out due to low number of patients in this early study. [Table: see text]
Retrospective analysis of ipilimumab-induced diarrhea and/or colitis: A single centre review.
Authors: Iafolla Marco Adelmo James , Pond Gregory Russell , McWhirter Elaine
Published: September 2018

e21064

Background: Ipilimumab is an effective medication in advanced melanoma but can cause severe diarrhea and colitis. This study identified the rate of ipilimumab-induced diarrhea/colitis at the Juravinski Cancer Centre (JCC), its associated factors for development, overall survival (OS) and progression free survival (PFS). Methods: The Ontario Patient Information System was used to retrospectively identify all melanoma patients at the JCC who were treated with ipilimumab 3 mg/kg IV every 3 weeks (September 2012 to June 2016). Patient demographics, medical history, prior melanoma treatments, diagnosis of ipilimumab-induced diarrhea/colitis, interventions to treat the diarrhea/colitis, and OS and PFS were collected. Descriptive statistics summarized characteristics and outcomes. Kaplan-Meier methods estimated time to event outcomes. Cox regression evaluated whether markers were prognostic for time to diarrhea/colitis diagnosis. Results: 71 patients were treated with ipilimumab at the JCC, of which 22 patients (31%) developed diarrhea/colitis of any Grade; 4 patients developed Grade 1, 5 patients Grade 2, 6 patients Grade 3, 3 patients Grade 4, and 4 patients had unclear Grade. 11 patients required prednisone 1-2 mg/kg and 2 patients required anti-TNF treatment to treat their diarrhea/colitis; 1 patient required colectomy due to perforation. 10 patients required treatment discontinuation due to diarrhea/colitis. Whole cohort median OS and PFS was 340 days (95% CI 205, 519) and 110 days (95% CI 91, 138), respectively. Univariate analysis showed that only inadequate hematologic function at time of first ipilimumab application was prognostic of diarrhea/colitis (HR = 6.42, 95% CI 1.44, 28.62; p = 0.015). Conclusions: Our OS, PFS, and rate of all grade ipilimumab-induced diarrhea/colitis are similar to published data, however our rate of Grade > 2 is larger. Additional work is needed to identify risk factors for the development of this immune related adverse event.
Whole-body MRI (WB MRI) including diffusion weighted (DW) imaging for the surveillance of melanoma patients at high risk for recurrence following surgery or systemic therapy.
Authors: Jansen Yanina , Willekens Inneke , Brussaard Carola , Neyns Bart
Published: September 2018

e21072

Background: Patients (pts) with locally advanced melanoma have a high risk of recurrence following complete surgical resection of macrometastases. Recent therapeutic progress has led to a growing number of stage IV pts achieving a durable complete remission (CR). For both populations no standards are established for surveillance with medical imaging. This prospective study explored the usefulness of surveillance by WB MRI for the early detection of melanoma recurrences. Methods: Pts with advanced melanoma (AJCC stages IIIb/-c or -IV) who were disease free following resection of macrometastases (cohort 1) and pts in CR following immunotherapy (cohort 2) were included. All pts underwent WB MRI, includingT1, Short Tau Inversion Recovery and DW imaging, Q4 mths the first 3 years of follow-up and Q6 mths in the following 2 years. Results: From Oct 2014 to Jan 2017, 43 pts were included (26 pts in cohort 1; 17 in cohort 2). 4 Pts were excluded (pacemaker [1pt], claustrophobia [1 pt], clinical recurrence before the first MRI [2 pt]). Mean follow-up was 103 wks (range 14–127). In total, 182 WB MRIs were performed (median number per pt: 4.5 [range 3-7]). A total of 16 pts were diagnosed with suspected lesions on WB MRI. Of these, 8 pts were diagnosed with melanoma recurrences (7 pts in cohort 1 and 1 pt in cohort 2). A total of 8 suspected lesions (8 Pts) identified on MRI (4 lymph node, 1 muscle, 1 bone, and 2 liver lesion) were considered to be of non-neoplastic origin based on additional diagnostic imaging and follow-up. No invasive procedures resulting in a false negative result were triggered by MRI. In 2 pts from cohort 2 a solitary subcutaneous metastasis was first detected by clinical examination (1 could be identified on MRI retrospectively, 1 was found in between MRIs). WB MRI was safe without any clinically meaningful ( > gr1) adverse event. Conclusions: Exploration of WB MRI for the surveillance of melanoma patients following resection of melanoma macrometastases or CR on systemic therapy indicates that it is a safe and sensitive imaging technique sparing patients cumulative exposure to x-rays and contrast media. Clinical trial information: NCT02907827.
Use of intermediate clinical endpoints (ICE) as a primary efficacy endpoint in malignant melanoma.
Authors: Narayanan Siva , Shao Dong , Shah Anshul , Ramesh Vidya
Published: September 2018

e21075

Background: Melanoma incidence in the US has seen a considerable increase, from 17.8 (1997) to 24.0 (2013) per 100,000, with localized melanoma accounting for 84% of all cases. Early detection and treatment can improve outcomes considerably, resulting in a 99% survival rate. The FDA, within its accelerated approval program, accepts ICE as a primary endpoint, shortening time for patient access to life saving medications. Our objective was to study use of ICE as a primary endpoint for therapies targeting non-metastatic/early-stage malignant melanoma. Methods: A systematic review was conducted in PubMed to identify clinical trials using ICE as a primary endpoint in early stage (non-metastatic, stage I or II) malignant melanoma. An additional search was conducted in clinicaltrials.gov to identify ICE as a primary endpoint in on-going malignant melanoma trials (assess evidence body being built). Searches were limited to the English language, between November 2011 and October 2016. Studies reporting only overall survival (OS) as the primary endpoint were excluded. Results: Of the 226 titles and abstracts screened from PubMed, seven trials were included in the analysis. Of 440 records screened from www.clinicaltrials.gov, one was included, resulting in eight studies of randomized phase 3 trials. Relapse-free survival (RFS) and disease-free survival (DFS) were reported in 3 trials each, and represent the most frequently reported primary ICE (38% each). RFS/DFS is defined as the time from randomization to recurrence of disease or death, and combined, encompass 75% of reported ICE. Other ICE reported were distant metastasis free interval (DMFI, 1 trial) and lymphnode field relapse (1 trial). One trial reported OS as a co-primary endpoint. Conclusions: Definitions of the most observed ICE in malignant melanoma, namely, RFS and DFS, appear to overlap, warranting further investigation into consolidation of outcomes to better assess the value of intermediate endpoints in early stage malignant melanoma. Findings indicate a slow, but growing body of evidence supporting ICE as a primary endpoint in malignant melanoma, bringing focus to prevention or delay of disease progression to alleviate patient burden.
Interleukin-2 (IL-2) and 5-(3,3-dimethyle-1-triazeno) imidazole-4-carboxamide (DTIC) for adjuvant therapy in resected high-risk primary and regionally metastatic melanoma.
Authors: Gosain Rahul , Gill Amitoj , Gragg Hana , Bycroft Ryan Glenn , Rai Shesh , Pan Jianmin , Chesney Jason Alan , Miller Donald M.
Published: September 2018

e21076

Background: High-dose interferon (IFN) and ipilimumab currently are the only approved adjuvant therapies for high-risk melanoma patients. We analyze the recurrence free survival (RFS), overall survival (OS), and toxicity profile of Interleukin-2 (IL-2) and 5-(3,3-Dimethyle-1-Triazeno) Imidazole-4-Carboxamide (DTIC) combination for resected high-risk primary and regionally metastatic melanoma patients as an alternative adjuvant therapy. Methods: Patients with stage IIB, IIC and stage III melanoma that were treated and received adjuvant IL-2/DTIC combination therapy at a single institution in the year 2000 to 2010 were retrospectively reviewed. No evidence of residual disease was noted prior to therapy. Regimen consisted of subcutaneous IL-2 at 12 x 106 units on days 1 through 4 every month and DTIC 750mg/m2 on day 1 of each cycle every 28 days for 6 cycles. Individual medical records were accessed to collect the data and the Kaplan-Meier method was used to estimate RFS and the OS. Results: Of the 112 patients included, all underwent surgery and then received adjuvant treatment. 109 patients were followed and 3 were lost to follow-up. 59% of the patients were male, 41% were female. 79 (70.5%) of the patients were alive at the time of analysis and 57 patients were currently event free. 69 (61.61%) of the patients completed all 6 months of adjuvant combination treatment with 22.3% of the patients requiring DTIC and 15.2% of the patients’ required IL-2 dose reduction. 2-year OS (from the day of surgery) was 92.85% (95% CI of 86.29-96.53) with RFS of 66.31% (95% CI of 56.92-74.49) and 5-year OS was 75.57% (95% CI of 64.72-83.50) with RFS of 53.05% (95% CI of 41.91-62.58). Conclusions: With little improvement in the RFS from IFN and high toxicity profile with ipilimumab, neither of these treatment regimens seem to be an ideal option. In our retrospective analysis, combination therapy with IL-2/DTIC appears to be beneficial and well tolerated as an alternative adjuvant treatment for patients with high-risk melanoma, but this observation requires further prospective validation.
Patient centered outcomes for skin cancer treatment: A single day Delphi process to assess the importance of treatment themes to a representative panel of skin cancer patients.
Authors: Maher Ian , Alam Murad , Bordeaux Jeremy S , Cartee Todd , Baum Christian , Rossi Anthoy , Lawrence Naomi , Behera Anit , Armbrecht Eric S.
Published: September 2018

e21079

Background: Increased emphasis is being placed on patient centered outcomes. There is little existing literature on the patient population's prioritization of outcomes in skin cancer care. A PCORI-supported Patient Outcomes Summit was organized to address this. Methods: Patients were recruited from patient support groups, solicitation of ASDS member practices, as well as personal recruitment of patients from the practices of the investigators. A one-day Patient Outcome Summit was convened in Arlington, VA in August 2016. Patients attendees were given orientation to existing outcomes for skin cancer as well as the Delphi process. They then participated in a two round Delphi process by run non-physician facilitators (AB and EA). Group discussion was used to solicit outcomes for inclusion in the rating rounds. Outcomes were then rated anonymously on a 1 (lowest relevance) to 9 (highest relevance) scale. Patients were then able to view the anonymous feedback of the group and rerate the items as they deemed fit based on the group feedback. Results: 21 patients participated in the Delphi process (5 men and 21 women). 10 were melanoma and 11 were non-melanoma patients. 56 treatment related outcomes and themes were identified. The ten most highly rated themes are shown in the table. Conclusions: The first ever skin cancer patient outcome summit was convened to address the lack of patient-centered data in the skin cancer literature and guide measure development. Some traditional outcomes (recurrence) were identifiend. However, the majority of the themes rated most important by the patient attendees center around inclusion of the patient in the decision making process and the physician-patient communication. Increased emphasis and education in these domains may drive increased patient satisfaction in skin cancer care. [Table: see text]
Setting and timing of end-of-life care in cancer patients.
Authors: De Carlo Elisa , Gerratana Lorenzo , Cinausero Marika , Vitale Maria Grazia , Buoro Vanessa , Bonotto Marta , Ermacora Paola , Sacco Cosimo Stanislao Pio , Puglisi Fabio , Fasola Gianpiero
Published: September 2018

e21502

Background: Limited data are available on how the setting and timing of palliative care (PC) referral can affect end-of-life (EoL) care and survival in cancer patients (pts). The aim of our study was to evaluate the impact of PC referral (hospice and/or home-care services) versus family physician care (FP-C), in terms of both EoL quality of care and survival in cancer pts. Methods: The study included 337 cancer pts who died between January 2015 and February 2016. We retrieved data on type of EoL care and on poor quality of care indicators in the last 30 days of life. Palliative Care Survival (PCS) was defined as the interval between timing of PC referral and death. The survival after treatment (Treatment-Free Survival, TFS) was defined as the interval between the last administration of anticancer therapy and death. Results: FP-C court included 89 pts and PC services court 248 pts. The 248 PC pts were divided in three groups: 99 assisted by both PC services, 58 only by home-care and 91 only by hospice care. The median PCS was 24 days. TFS was significantly longer for the three groups assisted by PC (105, 95, and 82 days respectively) than for that assisted only by FP-C (49 days, p < 0.0001). Compared to PC services, FP-C was associated with higher frequency of poor quality of care indicators, such as emergency room visits (p < 0.0001), hospitalizations (p < 0.0001), hospital death (p < 0.0001) and chemotherapy administration (p < 0.0001). In addition, earlier PC referral (30-60 and > 60 days before death) versus late referral ( < 30 days before death) was associated with a lower frequency of poor quality indicators. Variables such as age, sex and primary tumor were not associated with a different quality of care. Conclusions: Pts referred to PC services, compared to pts referred only to FP-C, had improved EoL survival and quality of care. A better definition of PC referral timing can affect the quality of EoL care in cancer pts.
A practical clinical score to predict early death after a comprehensive geriatric assessment (CGA) in elderly cancer patients: A prospective cohort study with 608 patients.
Authors: Telles O Lima Jurema , Bergmann Anke , Mello Maria Julia Gonçalves , Cavalcanti Zilda , Bezerra Mirella Rebello , Sales Letícia telles , Thuler Luiz Claudio Santos
Published: September 2018

e21537

Background: Components of the comprehensive geriatric assessment (CGA) correlate with risk of early mortality in elderly cancer patients (ECP). However, its complexity and the time required for its administration. The aim of this study was to determine the impact of each CGA domain on overall survival(OS) and to first step for the development of a prognostic scoring system to stratify ECP. Methods: a prospective cohort study. Participants with a recent diagnosis of cancer were from eight hospitals and one cancer center in Brazil and were recruited during their first medical appointment at the outpatient oncologic clinic. A basal CGA was done before the care decision (ADL, Charlson Comorbidity Index- CCI, Karnofsky Performance status – KPS, GDS15, IPAQ, MMSE, MNA, MNA-SF, PS, PPS, Polipharmacy, QLQc30, TUG). During the follow up of six months, information about the treatments performed and early death was collected. OS was estimated using the Kaplan–Meier method, and survival curves were compared using the Log rank test for categorical variables. A multivariate Cox proportional hazards model was used to select early death risk factors. A clinical score considering the number of risk variables was created. Results: From 2015-2016, 608 ECP, mean age 71.9 (SD ±7.4; range 60-96), 50.7% male, were enrolled. 100 (16.4%) ECP died in less than six months of follow-up. In our multivariate model, controlled by age, site of cancer and cancer stage, the remaining significant risk factors were malnutrition/nonutrition determined by MNA (HR 3.3, 95%CI 1.81-5.99, p < 0.001), KPS < 50% (HR 2.44, CI 1.56-3.81, p < 0.001) and CCI > 2 (HR 1.6, CI 1.09-2.52, p = 0.018). The risk for early death according to the number of risk variables: three (HR 12.99, CI 5.69-29.60, p < 0.001), two (HR 5.65, CI 2.61-12.24, p < 0.001) or one (HR 2.7, CI 1.28-5.87, p = 0.009). Conclusions: a practical clinical score using three instruments of the CGA (MNA, KPS and CCI) can predict independent the risk for an early death in ECP. The development of a practical system for risk scoring, incorporating few clinical prognostic factors, helps to stratify patients into risk groups and to plan a personalized care.
Prospective validation of a novel geriatric screening tool, the Korean cancer study group geriatric score (KG)-7, in older patients with advanced cancer undergoing 1st line palliative chemotherapy.
Authors: Kim Jin Won , Kim Se Hyun , Lee Yun-Gyoo , Hwang In Gyu , Song Hong-Suk , Koh Su-Jin , Ko Yoon Ho , Shin SeongHoon , Woo In Sook , Hong Soojung , Kim Tae Yong , Baek Ji Yeon , Kim Hyun Jung , Kim Hyo Jung , Lee Myung Ah , Kwon Jung Hye , Hong Yong Sang , Ryoo Hun-Mo , Lee Kyung Hee , Kim Jee Hyun
Published: September 2018

e21540

Background: Full geriatric assessment is time-consuming and labor intensive, and most screening tools were developed in Western countries, which cannot reflect differences in some domains such as nutrition deficit, in Asians. Methods: This prospective study to validate a novel geriatric screening tool, the Korean Cancer Study Group Geriatric Score (KG)-7, was conducted as a substudy of a multicenter study for the prediction tool of toxicity in older cancer patients receiving 1st line chemotherapy (KCSG PC13-09). Abnormal GA was defined as deficits in at least 2 out of 6 domains [activities of daily living (ADL), Korean-instrument ADL (K-IADL), Mini-Mental Status Examination in the Korean version of the Consortium (MMSE-KC), Short-Form Geriatric Depression Scale (SGDS), the Mini Nutritional Assessment (MNA), Timed Get Up and Go test (TGUG)]. KG-7 questionnaire was answered before full GA. We compared the performance of KG-7 with G-8 score, obtained from MNA, by calculating AUC of accuracy, and also sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV). Results: Baseline GA and KG-7 results of 301 patients were collected. Median age was 75 years old (range 70-93). Eighty six (28.6%) and 124 patients (41.2%) showed dependent ADL and IADL, respectively. Impairment for domains of MMSE, SGDS, MNA, and TGUG was identified in 166 (55.1%), 132 (43.9%), 230 (76.4%), and 52 patients (17.3%), respectively. Abnormal GA was documented in 221 patients (73.4%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, the AUC was 0.741 (95% CI, 0.683-0.800), and the SE, SP, PPV, and NPV were 75.6%, 58.7%, 84.3%, and 44.9%, respectively. Abnormal KG-7 score was shown in 198 patients (66.9%). With the ≤ 14 cut-off value of G-8 for abnormal GA, the G-8 showed a SE, SP, PPV, and NPV of 93.6%, 28.0%, 79.2%, and 60.0% with AUC of 0.766 (95% CI, 0.703-0.829). Abnormal G-8 score was shown in 260 patients (88.1%). Conclusions: KG-7 could identify patients with abnormal GA with comparable performance with G-8 and can be a useful screening tool for Asian countries with limited resources and high patient volume.
Association between health status and social integration/loneliness in survivors of adolescent and young adult (AYA) cancers.
Authors: Huang I-Chan , Jones Conor , Srivastava Deo Kumar , Hudson Melissa M. , Robison Leslie L. , Krull Kevin R.
Published: September 2018

e21563

Background: AYA cancer survivors are at risk of various adverse health outcomes, but the relation between health status, social integration (i.e., social network and support) and loneliness is understudied. Methods: 102 AYA survivors (mean age = 25 years; diagnoses = leukemia 27%; lymphoma 24%; brain tumors 9%; solid tumors 41%) and 102 age-sex-matched controls were recruited from a community-based online panel. Participants reported social network information (e.g., contact frequency, resources for health counseling) for up to 25 of closest friends/relatives, which was used to create a functional social network index. UCLA Loneliness Scale, Duke-UNC Functional Social Support Questionnaire and PROMIS Health Profile were used to measure loneliness, social support and health-related outcomes (physical functioning, depression, anxiety, fatigue and pain), respectively. Multiple linear regression was used to compare functional social network, social support and loneliness between survivors and controls, and to assess the relation between health outcomes and perceived loneliness. Results: Compared to controls, survivors of lymphoma (b = 1.98; p = 0.005), leukemia (b = 1.67; p = 0.012) and solid tumors (b = 1.22; p = 0.030) had a higher functional social network index. However, social support did not differ between survivors and controls (p’s > 0.05). Brain tumor survivors (b = 15.65; p = 0.006) and solid tumor survivors (b = 10.83; p < 0.001) had more loneliness than controls. Compared to low loneliness controls, high loneliness survivors had significantly lower physical functioning (b = -7.72; p < 0.001) and higher anxiety (b = 8.35; p < 0.001), depression (b = 10.57; p < 0.001), fatigue (b = 5.52; p = 0.011) and pain (b = 6.37; p < 0.001) after adjusting for age, sex, education, social integration, and number of self-reported chronic health conditions. Conclusions: Loneliness is significantly associated with poor health-related outcomes in AYA survivors, which is independent of the influence of social integration. Future research is warranted to understand the relation between health status and social interactions among AYA survivors to inform intervention-based strategies.
Utility of a novel smartphone application for breast cancer survivors.
Authors: Kell Malcolm R. , Barry Mitchell
Published: September 2018

e21577

Background: Breast cancer survivorship aims to improve quality of life and reduce the risk of relapse after diagnosis and treatment. Smartphone applications are now widely used and facilitate many daily activities. Excercise and diet are key components of survivorship and modification of both can improve longterm breast cancer outcome. We have developed a smartphone application focused on enhancing excercise and diet following breast cancer diagnosis; Breast Cancer Survivor. Methods: A Smartphone application was developed with Portable Medical Technology, Ireland (https://itunes.apple.com/ie/app/breast-cancer-survivor/id1043485265?mt = 8). We focused on improving excercise and caloric balance to reduce body mass index. The appliction measured excercise, intensity and distance, to calculate individual energy expenditure and set a target aimed at reducing BMI by 10% over 8 weeks. In additon to excercise we gave dietry advice to focus on caloric intake. We have examined both national and international usage of the application after it was realeased free of charge, for the initial 6 months after release. Results: 770 users donwloaded and used Breast Cancer Survivor in the initial 6 months. Majority of users were in Ireland (38% n = 534), United Kingdom (24.6% n = 339) and United States of America ( 10.7% n = 147). 1376 session of use were recorded and off these 44.2% (n = 608) were return users. BCS app was used for an average of 2.2 minutes per session.Following initial release and local media coverage usage peaked at 401 sessions and then plateaued at 118 sessions after 6 months with only social media coverage. Conclusions: Smartphone application is an effective lifestyle modification, targeting breast cancer survivors. Breast Cancer Survivor has been widely used with only limited promotion. Breast cancer survivorship can be promoted with a smartphone application.
Metastatic Breast Cancer Collateral Damage (MBCCD) project: Addressing unique needs and identifying patients at highest risk.
Authors: DeHart Jessica Noelle Clague , Stanton Annette , Eshraghi Leah , Cooper Ortner Heather , Williamson Timothy , Jorge Alexandra , Obidegwu Nwamaka , Love Susan M.
Published: September 2018

e21592

Background: From The Health of Women (HOW) Study™, we found that participants living with metastatic breast cancer (MBC) had a considerably diminished quality of life (QoL) compared to those with less advanced breast cancer. When faced with MBC, managing and minimizing collateral damage (CD) resulting from sequential and often continuous treatments is crucial to improving QoL. The aim of the MBCCD Project was to characterize the unique experience of MBC in order to identify and address potential areas of need in this underserved population. Methods: We crowdsourced input and gathered free-text data from 353 MBC patients to document the breadth of CD affecting QoL. We then developed a new questionnaire using validated QoL scales and PROMIS measures, along with a novel assessment of Living with MBC derived from the crowdsourcing data, which, in some cases, included verbatim statements from patients. Results: Among the 515 MBC respondents, the median age was 57 years (28-86 years), and the majority was female (99%) and non-Hispanic White (91%). Patients retrospectively reported a significant decline in overall QoL after MBC diagnosis (Before MBC: 51% excellent and1% poor/extremely poor; After MBC diagnosis: 12% excellent and15% poor/extremely poor; p < 0.05). As expected, considerable CD was reported in every aspect of the patients’ lives—physical, social, financial and psychological. MBC patients who were younger ( < 50 years), had lower financial status, and/or reported having children under the age of 18 years living at home were identified as being at highest risk of significant CD in every category (p < 0.05). Contrary to common belief in the clinical setting, CD did not vary as a function of treatment type or metastatic location. Conclusions: Findings illustrate the need for dynamic and personalized strategies targeting CD to improve the health and well-being of MBC patients. Within each area of CD, critical needs and subsets of patients at highest risk were identified. Next steps include increasing diversity and working with MBC advocates and provider-survivor collaborators to develop recommendations that maximize benefit to MBC patients while remaining feasible for providers.
Does screening for anxiety and depression efficiently identify patients who want help?
Authors: Jacobs Linda A. , Blauch Abigail N. , Pucci Donna A. , DeMichele Angela , Palmer Steven C
Published: September 2018

e21604

Background: Screening cancer patients for psychosocial difficulties is recommended as a means of identifying individuals in need of assistance and improving outcomes. Although screening may identify individuals at risk for difficulties, it is unclear if screening a) identifies those willing to accept assistance or b) may have the consequence of rationing care away from those who want assistance but screen negatively. We examined these issues in a sample of breast cancer (BC) survivors. Methods: Consecutive non-metastatic BC survivors > 1 year from end of treatment completed an online assessment including the Hospital Anxiety and Depression Scale and patients' desire for assistance with Anxiety and Depression prior to their survivorship visit. Results: Participants (N = 260) were predominately white (81.5%), college educated (81.2%), married/partnered (74.6%), and had an annual income of $60,000 or greater (69.3%). Most were diagnosed Stage I (48.3%) or Stage II (33.5%) BC, and underwent surgery (100%), chemotherapy (60.9%), and/or XRT (70.1%). Mean depression (M = 3.89; SD = 3.73) and anxiety (M = 6,63; SD = 4,47) scores were low and below the established cut point of 8 (all t > -5.0; all p < .001 ), although 20.7% and 42.3% screened positively for depression or anxiety, respectively. Screening positive for depression or anxiety was significantly associated with a desire for intervention (all X2> 22.0; all p < .001 ). However, only a minority of those screening positive for depression (32.1%) or anxiety (34.5%) desired intervention. The number of individuals screening negative but desiring intervention compared to those screening positive and desiring intervention was 76% for depression and 50% for anxiety. Conclusions: Most BC survivors screening positive for depression or anxiety do not desire intervention, at least within the cancer setting. In absolute numbers those screening negative, desire intervention relative to those screening positive at rates of 50-76%, representing a missed opportunity to improve outcomes. Screening without exploring desire for intervention may over identify individuals who do not desire help while missing a relatively large number of those who possibly may.
Quality of life and satisfaction with care in a contemporary cohort of pancreatic cancer patients.
Authors: Abdel-Rahman Omar , Renouf Daniel John , Schaeffer David F. , Cheung Winson Y.
Published: September 2018

e21623

Background: Pancreatic cancer patients face significant disease- and treatment-related morbidity while management is frequently complex. With recent advances in radiation and surgery and the introduction of new systemic therapy regimens, understanding these patients’ quality of life (QOL) and their satisfaction with the care that they currently receive is essential to inform the design of future care delivery models. Methods: Pancreas Centre BC was established in British Columbia in 2012 to promote efficient triage, rapid access to multidisciplinary care, and early involvement of palliative care, if necessary. Consecutive pancreatic cancer patients who were referred to and seen at Pancreas Centre BC completed the EORTC-QLQ C30 and PAN26 questionnaires before and after surgery as well as surveys focused on the levels of satisfaction with their disease management. Using independent samples t-tests, we correlated clinical characteristics with QOL and satisfaction scores. Results: In total, 167 patients were included: median age was 63 years, 45% were men, and 70% were ECOG 0/1. The majority had early stage disease (78%), pancreatic head tumors (53%), adenocarcinoma histology (68%), and adjuvant gemcitabine (75%). Baseline mean QOL scores were 63, 90, 83, 58 and 92 (out of 100) in the overall, physical, emotional, cognitive and social domains, respectively. Advanced age ( > 70 years), weight loss ( > 10 kg), and poor ECOG were independently associated with lower overall QOL rating (all p > 0.05). Surgery had a positive impact on all functional domains where we observed a mean improvement in QOL scores ranging from 8 to 17 points (all p > 0.05). In terms of satisfaction, 94% of patients rated their overall care as good to excellent. Likewise, 80% of patients were very or mostly satisfied with the amount of information they received and 84% of patients rated the healthcare information they received as very or mostly helpful. Conclusions: Despite the morbidity of pancreatic cancer, patients referred to and seen at a tertiary pancreatic cancer center reported good QOL and satisfaction levels, suggesting that the centralization of pancreatic cancer care may be an effective model to address the high priority needs of this population
Feasibility of monitoring of body temperature for patients undergoing stem cell transplant or intensive chemotherapy.
Authors: Dambrosio Nina , Gannon John , Eager Jon , Sylvan David , De Lima Marcos J.G. , Levitan Nathan , Malek Ehsan
Published: September 2018

e21630

Background: Early detection of fever and prompt use of broad-spectrum antibiotics is crucial in neutropenic patients (pts). Episodic monitoring of temperature serves as standard-of-care (SOC) method in inpatient settings may suffer from delay in fever detection, whereas self-reported fever can be less reliable in the outpatient setting. Therefore, a continuous real time method of body temperature measurement may serve as a clinical decision support tool to improve outcomes. In this study, we proposed to test a device that continuously monitors body temperature. Methods: Pts admitted for stem cell transplant or high dose chemotherapy for leukemia were included. Body temperature was measured every 4 hours as SOC throughout hospital stay. Temperature Rise (TR) was defined as spikes above 100.4 °F. We used TempTraq patch (Blue Spark, Ohio), a FDA class II device, to monitor body temperature in real time. It transmits the data to a receiver (iPad or Smartphone) via Bluetooth to display body temperature data with the ability to set alerts. A questionnaire was designed to capture patient’s adherence, compliance and satisfaction. Results: The patches were applied every 24 hours on 10 pts throughout hospital stay. Body temperature was recorded remotely with 10 minutes intervals (14, 342 temperature measurements). There were 23 episodes of TR among all pts by SOC method, 21 of them were detected by the patch with a median of 140.1 minutes (range: 30-180 minutes) sooner than SOC. The patch data was successfully transmitted and displayed on the study iPad invariably. Ten out of 10 pts were able to wear the patch daily through hospital admission and felt the patch was easy to apply. Nine out of 10 pts felt the patch was comfortable and did not irritate their skin. Eight out of 10 pts were interested in wearing the patch for temperature monitoring in future. Eight out of 10 pts were completely satisfied with the patch. Conclusions: Our data suggest that real time body temperature measurement by the patch sensor used in this study is feasible and convenient. Also, it is able to detect the rise in temperature earlier in majority of cases. Further studies to assess reliability of this device in outpatient setting are warranted.
Association of paclitaxel to lipid nanoparticles in the treatment of bone metastasis in patients with solid tumors.
Authors: Graziani Silvia Regina , Vital Carolina Graziani , Morikawa Aleksandra Tiemi , Fernandes Hezio Jadir , Naime Fauzia de Fátima , Fonseca Ricardo Oliveira Da , Dias Carla Andressa Rodrigues , Almeida Ligia Rabello De , Neto Raphael Francisco Azuaga , Yamada Karina Emi , De Abreu Maria Stella Sa Granja , Pontes Tatiana Caldeira , D'Alvia Thiago , Ferreira Rafael Sanches , Eyzaguirre Velasquez Arianne Renata , Orias Valéria Urresti , Vanderlinde Fabiano Garcia , de Almeida Leandro Maritan , Diniz Paula Calixto Batistela , Maranhão Raul Cavalcante
Published: September 2018

e21631

Background: Bone metastasis occurs in more than 65-90% patients with hormone-dependent solid tumors, as breast and prostate cancer, with slow evolution, being not responsive to standard chemotherapeutic agents, which restricts treatment options. Previously, we have shown that lipid nanoparticles resembling LDL-cholesterol-like are uptake in malignant tissues and capable of delivery anti-cancer drugs, after intravenous injection. The delivery of drug drastically reduced toxicity. The objective of this study was to evaluate the clinical responses to treatment with paclitaxel associated to nanoparticles, laboratory toxicity and pain scale in patients with breast and prostate carcinoma, previously treated with conventional schemes chemotherapy and not eligible for subsequent treatment. Methods: We included six patients with prostate carcinoma, and ten patients with breast carcinoma (age 68 ± 4 and 55 ± 7 years, respectively). All patients had advanced clinical staging IV at diagnosis (TNM-UICC classification). Treatment consisted in the combination of paclitaxel to lipid nanoparticles (dose: 175 mg/m2 body surface), intravenous, every 21 days, without premedications. Biochemistry determinations were performed before onset and every three weeks during treatment. To assess pain, we used the Verbal Analogue Scale (from zero to 10) and the use of opioids in the treatment period. Results: Total of 64 cycles were performed without clinical or laboratory toxicity. At the beginning of treatment the pain score was 8 (range 6-9), after six weeks it reduced to a mean of 6 (range 4-8) and after 18 weeks reduced to 4 (range 2-8). Six patients required 180 mg/day of morphine, but after 12 weeks the dose was reduced to 60 mg/day. Six patients progressed after three cycles requiring use of potent analgesic. Conclusions: The notable absence of toxicity and significant improvement in pain indicate paclitaxel associated to lipid nanoparticles as a promising option in chemotherapy regimens.
Neurotoxicity associated with anti-PD1 therapy: A multi-center case series.
Authors: Smith Jess Louise , Menzies Alexander M. , Cohen Justine Vanessa , Lioret Margarida Mut , Ozgun Alpaslan , Spain Lavinia , Park John J. , Johnson Douglas Buckner , McQuade Jennifer Leigh , Feng Sophie , Sandhu Shahneen Kaur , Atkinson Victoria , Tsai Katy K. , Long Georgina V. , Larkin James M. G. , Eroglu Zeynep , Sullivan Ryan J. , Henderson Andrew , Carlino Matteo S.
Published: September 2018

e21641

Background: The anti-PD1 antibodies (PD1) pembrolizumab and nivolumab are now FDA-approved in multiple malignancies. With increased use, rarer immune-related adverse events (irAEs) not well characterized in clinical trials are being identified, including neurotoxicities. Methods: Patients (Pts) who developed neurotoxicites while being treated with PD1 (alone or in combination) were retrospectively identified from 10 cancer centers. Data regarding treatment, toxicity and outcome were examined. Results: 40 pts (38 melanoma and 2 non-small cell lung cancer pts) developed neurotoxicity; 14 on anti-PD1 monotherapy, 23 in combination or sequence with ipilimumab, and 3 on blinded trials or in combination with interferon. The overall response rate was 90% and median progression free survival was not reached. The median time from treatment initiation to development of neurotoxicity was 7 weeks (range 1-86.5 weeks). 8 pts had died, 5 from disease progression and, 2 from neurotoxicity. 26 pts (65%) developed other irAEs. 27 (67.5%) pts developed toxicities affecting the peripheral nervous system including motor sensory neuropathies (6), sensory neuropathies (4), and Myasthenia Gravis (3). 13 (32.5%) pts developed central nervous system toxicities including aseptic meningitis (6) and encephalitis (4). 24 (60%) pts were treated with steroids alone. 9 pts required further immunomodulation including IVIG (7), plasmapheresis (3), MMF (1) and rituximab (1). 17 (43%) had complete resolution of symptoms, 5 (13%) had stable or worsening neurological disease, and 22 ( 55%) were improving at the time of datacut . 10 pts were retreated with PD1, of which 2 developed exacerbation of prior neurological symptoms. Conclusions: While rare, a variety of neurotoxicities can occur with PD1 treatment. Management may require immunomodulation beyond corticosteroids. Given the high response rate observed in this cohort, such toxicities and their management do not appear to negatively impact treatment response.
A pilot study of lactoferrin in patients with self-reported, chemotherapy-induced taste and smell abnormalities.
Authors: Lesser Glenn Jay , Case Doug , Wang Aili , Dietrich Andrea , Duncan Susan
Published: September 2018

e21643

Background: Taste and smell abnormalities (TSA) are common in patients receiving chemotherapy and may lead to food avoidance, altered nutritional intake, treatment delay or withdrawal, diminished socialization and impaired overall quality of life. Lipid peroxidation of mucosal cell membranes in the oral cavity is one cause of TSA and lactoferrin (LFN), an iron-binding protein normally present in saliva, is an effective scavenger of lipid byproducts that can decrease metallic flavor in healthy volunteers. Methods: Eligible patients with colorectal or pancreatic adenocarcinoma and self-reported TSA while on an oxaliplatin-containing chemotherapy regimen were treated with LFN 250mg three times daily for 4 weeks and then followed for an additional 4 weeks off study drug. A second identical IRB-approved pilot trial enrolled patients with solid tumors, lymphoma or myeloma with self-reported TSA while receiving chemotherapy. The primary outcome was the change in self-reported TSA following 4 weeks of LFN as measured by a validated taste and smell questionnaire (TSQ) consisting of taste (score 0-10) and smell (score 0-6) subscales, which are combined to yield a total composite score (0-16, 0 = no TSA). The TSQ was assessed at 0, 4 and 8 weeks along with the FAACT (FACT–G + anorexia subscale), salivary protein and metals analyses, and the Brief Smell Identification test (B-SIT). Results: 26 total pts were enrolled (14 Males; mean age 60.5 years; range 32-79), and 19 and 17 pts remained on study with analyzable data at 4 and 8 weeks. Baseline mean taste, smell and composite TSQ scores for the 26 enrolled patients were 6.5, 3.1 and 9.6 units. After 4 weeks of LFN treatment, the mean overall TSQ score improved by 1.7 units (p = .018) while the taste and smell subscales improved by 0.6 (p = .062) and 1.1 units (p = .042) respectively. At 8 weeks, the mean TSQ score improved from baseline by 3.8 units (p < .0001) while the taste and smell subscales improved by 1.9 (p = .001) and 1.8 (p = .003) units. No significant change from baseline was recorded in the FAACT or the B-SIT at 4 or 8 weeks. Conclusions: These pilot data suggest that further evaluation of LFN in patients with self-reported TSA is warranted. A randomized trial is in development. Clinical trial information: NCT01941810, NCT01596634.