bluuebunny/crossref_metadata_2025 huggingface dataset:
Current treatment patterns and associated outcomes in Waldenström macroglobulinemia (WM) and related hematologic malignancies: A systematic literature review (SLR).
Authors: Tang Boxiong , Yang H. Keri , Caver Tony E. , Karcher Rachel , Trautman Holly
Published: May 2019

e18235

Background: The objectives are to review published literature and identify unmet needs for WM-related treatment and outcomes. Methods: A SLR using PubMed was performed to identify WM-related studies published Jan. 2013-Sept. 2018. Inclusion criteria included interventional or observational clinical studies with N > 40, non-case reports or editorial review, English abstracts available. Results: Of 1146 evaluable publications, 59 were included (40 real-world data [RWD], 4 clinical trials, 15 guidelines). Specific guideline recommendations varied due to limited comparative Phase III trials. RWD on safety and efficacy of WM treatment primarily included retrospective, single-center chart reviews or database analyses in mainly US and European populations. RWD showed heterogeneous WM treatment patterns and outcomes: (1) first-line chemoimmunotherapy use often did not follow guidelines; and (2) overall and progression-free survival (OS; PFS) with front-line regimens were lower than reported in trials. Reduced adherence, discontinuations (DC), and extended holds ( > 8-14 days) with kinase inhibitors (KI; ibrutinib or idelalisib) were common and associated with poorer outcomes (e.g. reduced OS or PFS) ( Table). Common reasons for KI DC/hold included toxicity, procedure/surgery, patient-request, and low/no disease activity. Conclusions: This SLR identified potential unmet needs in current WM treatment associated with poorer clinical outcomes, including KI DC, holds, and reduced adherence. Deviations from treatment guidelines were also reported. Future comparative clinical and RWE studies are needed.[Table: see text]
Is a delay in ALK inhibitor initiation associated with poorer survival? A retrospective analysis based on real-world data.
Authors: Sheinson Daniel , Wong William Bruce , Wu Ning , Mansfield Aaron Scott
Published: May 2019

e18240

Background: The time between a patient’s positive biomarker test result and initiation of targeted therapy may vary due to a number of factors, including the use of chemotherapy prior to or after the biomarker test result. The objective of this study was two-fold: first, to investigate the impact of delayed ALK inhibitor (ALKi) therapy on overall survival (OS) and second, to examine the association between the use of chemotherapy prior to or after biomarker testing and OS. Methods: The Flatiron Health EHR-derived database was used to identify patients with ALK-positive (ALK+) advanced NSCLC diagnosed between 1/1/2011 - 9/30/2018. The median time from ALK+ test result to ALKi start was used to separate patients into early versus delayed treatment cohorts. To account for potential immortal time bias, times from ALK+ test result to ALKi start from the delayed cohort were sampled with replacement and used to create modified index dates among the early cohort. Cox proportional hazards models adjusting for baseline characteristics (i.e. ECOG) were used to assess the association between delayed ALKi start and OS and the use of chemotherapy with OS. Results: 422 patients with ALK+ aNSCLC were included in this analysis with a median time from test result to ALKi start of 3 weeks. 88 patients (20.9%) received chemotherapy prior to starting their ALKi. Delayed ALKi use was associated with a 2.3 fold increase in risk of mortality (HR [95% CI]: 2.30 [1.28, 4.15], p < 0.01). There was no difference in survival observed between those who had received chemotherapy prior to initiating their ALKi and those who did not receive chemotherapy (HR [95% CI]: 0.99 [0.62, 1.58]). Among those who initiated chemotherapy prior to their ALK+ test result, the continued use of chemotherapy prior to initiating an ALKi did not result in differences in OS compared to those who switched to an ALKi without continuing chemotherapy (HR [95% CI]: 1.03 [0.44, 2.41]). Conclusions: Delayed initiation of ALKi may result in poor outcomes in patients with ALK+ NSCLC. Receipt of chemotherapy prior to ALKi or the duration of chemotherapy did not impact survival. Future strategies to improve the time to therapy initiation may be useful in improving patient outcomes.
Employment outcomes and quality of life in patients with early breast cancer and their support persons: A dyadic study.
Authors: Veenstra Christine M , Wittmann Daniela , McLeod Chandler , Braun Thomas , Hawley Sarah T.
Published: May 2019

e18241

Background: Many women with breast cancer face job loss related to their diagnosis, but little is known about employment outcomes among their partners and other supporters. Moreover, virtually nothing is known about associations between patients’ quality of life and supporters’ employment status. Methods: Breast cancer patients reported to Georgia and LA SEER registries in 2014-15 (N = 2,502, 68% RR) and their key decision support person (DSP) were surveyed separately. 1234 DSPs responded (71% RR). Patients and DSPs were asked about employment impacts of the patient’s breast cancer. Patients’ quality of life (QOL) was measured with the PROMIS scale for global health. Descriptive analyses of employment outcomes (job loss, missed days due to cancer) were generated for patients and DSPs. Associations between patients’ QOL and employment status of patients and their DSPs were assessed using linear mixed model regression analyses stratified by dyad type (partner vs. non-partner DSP). Results: Among DSPs, 43% were partners. 57% were non-partners (daughters, other family, friends). 67% were employed at time of patient’s diagnosis. Among these, 11% were no longer employed at survey completion. 39% missed > 30 days work. Non-partner DSPs were as likely as partners to lose their job or miss work because of the patient’s cancer. 65% patients were employed at diagnosis. Compared to patients whose DSP was a partner, patients with non-partner DSP were more likely to lose their job (39% vs. 24%; p < 0.01) or miss > 30 days work (55% vs. 45%; p < 0.01). For patients with a partner DSP, both patient and DSP employment at diagnosis were associated with improved patient QOL (each associated with a QOL score 24% of 1 standard deviation higher; each p < 0.05). For patients with non-partner DSPs, only patient employment at diagnosis was associated with improved patient QOL (QOL score 51% of 1 standard deviation higher; p < 0.01). Conclusions: Both non-partner and partner DSPs faced negative employment impacts related to patients’ breast cancer. Job loss and > 30 days of missed work were more likely among patients with non-partner DSPs. Only the employment of partner DSPs at diagnosis positively contributed to patients’ QOL.
Population kinetics of progression free survival (PFS).
Authors: Stewart David J. , Bossé Dominick , Robinson Andrew George , Ong Michael , Brule Stephanie Yasmin , Fung-Kee-Fung Michael , Hilton John Frederick , Clemons Mark J. , Ocana Alberto
Published: May 2019

e18251

Background: We assessed drug type impact on whether PFS curves could be fit by 2 phase decay models on nonlinear regression analysis (NLRA). Methods: We digitized 894 published PFS curves for incurable cancers. We used GraphPad Prism 7 for 1 phase and 2 phase decay NLRA, with constraints Y0 = 100 and plateau = 0. We defined curves as fitting 2 phase models if each subpopulation was ≥1% of the entire population and if subpopulation half-lives differed by a factor of ≥2, or if log-linear plots demonstrated unequivocal 2 phase decay. Results: PFS curves for single agents showed either high (≥75%) or low ( < 30%) probability of 2 phase decay, depending on drug type (p < 0.0001, Table). 11/11 PD1/ipilimumab combinations had 2 phase decay vs 36/209 curves (17%) for all other combinations. Conclusions: Drugs have either high or low probability of PFS curve 2 phase decay. Clinical trial methods or some mechanisms of acquired resistance might contribute to 2 phase decay, but 2 phase decay also could indicate a dichotomous factor (eg gene mutation/deletion or complete pathway silencing) producing 2 distinct subpopulations with differing progression rates. Drugs with high 2 phase decay could be prime candidates for RNA & whole genome sequencing, pathway expression studies etc to identify dichotomous predictive factors. Further assessment is needed to better understand why some drugs behave differently when given in combinations vs as single agents. [Table: see text]
The Quality Oncology Practice Initiative Program: Experience in Spain.
Authors: Lopez Rafael , Anton Antonio , Aranda Enrique , Carrato Alfredo , Constenla Manuel , Cruz Juan Jesús , Díaz-Rubio Eduardo , Feyjoo Margarita , García Foncillas Jesús , Gascon Pedro , Guillem Vicente , Lugo Ilse , Camps Carlos
Published: May 2019

e18267

Background: Patient care quality is a discipline with enormous relevance in today’s healthcare. Quality Oncology Practice Initiative (QOPI) is a referral worldwide in quality for oncology practices. The ECO Foundation is a collaboration of experts representing the major Spanish hospitals in the pursuit of excellence in cancer treatment. ECO reached an agreement with QOPI to involve Spanish hospitals in the QOPI program. Methods: 7 rounds of data collection have taken place (Fall 2015 to Round 2 2018). Practices had to register online and submit data into the QOPI platform, and the ECO Foundation offered them the necessary support. 18 Spanish hospitals have participated in the 7 rounds, and 12 of them have repeated participation. Core, Lung Cancer and Breast Cancer modules were completed. Results: During the 7 rounds, 2341 charts were submitted by the Spanish practices. The percentage of participating practices that presented results higher than 70% was successively 64%, 50%, 75%, 100% in the three following rounds and 88% in the last round. For the 12 hospitals that repeated participation, 8 reported improvements at different degrees of their global scores. These hospitals specifically show an improvement in the QOPI measures related to the signed patient consent for chemotherapy and the documentation of the patient consent in the practitioner note, the chemotherapy intent documentation, the appropriate completion of the chemotherapy planning, the documentation of the number of chemotherapy cycles and the development and documentation of the pain assessment. On the other hand, regarding QOPI Certification, three Spanish hospitals have received this accreditation in September 2017 and one in June 2018. Conclusions: These preliminary results are a good starting point for the continued implementation of the QOPI program in Spain, thus providing a well-structured approach to analyze cancer care. The ECO Foundation will continue pursuing excellence and quality with further activities like the QOPI Certification program and Quality Training Program, with these performed for the first time in Spain in 2017 and 2018 respectively.
Lack of clinician knowledge of human papillomavirus (HPV) vaccination to prevent HPV-related cancers in men: An interview study.
Authors: Varga Stefan , May Suepattra Grace , Morais Edith , Shrestha Anshu , Huber Caroline , Tantri Anupama , Roach Meaghan , Phillips Matthew , Jena Anupam B.
Published: May 2019

e18273

Background: Human papillomavirus (HPV) has a well-established link to cervical cancer and anogenital and oropharyngeal malignancies. Recognition of the HPV-caused cancer burden in males has led to expansions of female-only HPV vaccination programs to all genders. This study explored drivers of and barriers to gender-neutral HPV vaccination (GNV) program adoption, implementation, and potential impacts on the HPV-caused cancer burden. Methods: We conducted in-depth interviews with academic oncologists as well as advocacy, public health, infectious disease, and policy experts in six countries (Argentina, Australia, Austria, Brazil, Canada and Italy) from April-August 2018. Using a semi-structured discussion guide, we sought to elicit expert perceptions on factors affecting uptake of HPV vaccination in males and subsequent effects on the incidence of HPV-associated cancer. Data were analyzed for key themes. Results: Eighteen experts participated in the study, including three academic oncologists and two doctoral level oncology researchers. A key theme from the analysis was the critical need to promote education and awareness about GNV across all healthcare providers to facilitate vaccine uptake and high GNV coverage rates. Participants reported a lack of awareness among segments of practitioners about the effectiveness of the HPV vaccine in preventing HPV infection and associated cancers in all genders. They also described strategies to overcome knowledge gaps, such as partnerships with oncologists, cancer advocacy organizations, and professional medical societies, emphasizing the key role that all health care providers can play in raising awareness of the importance of HPV vaccination for all genders. Conclusions: Findings from this study suggest the need to enhance healthcare provider education about GNV, and the importance of a multi-specialty approach to promoting HPV vaccination to prevent infection and HPV associated morbidity and mortality in all genders.
Initial breast cancer consult: Improving satisfaction and impact on distress.
Authors: Decker Veronica B. , Ivanov Olga
Published: May 2019

e18284

Background: Goals of this performance improvement project were to: (1) determine the impact of initial breast cancer consultation on distress and number of reported problems as measured by the NCCN Distress Thermometer and Problem List (DT and PL) questionnaire and to: (2) explore the relationship between pre-consult DT and PL scores and patients’ satisfaction with information received during the consult as measured by the EORTC QLQ-INFO25. Methods: (1) Immediately prior to, and after, initial consult with the breast cancer surgeon, 59 convenience-sampled women completed NCCN DT and PL questionnaires. (2) They then completed an EORTC QLQ-INFO25 questionnaire designed to measure information satisfaction. Participants were placed in quartile groups based on DT score and, likewise, grouped based on number of reported problems on the PL. Quartile groups were then analyzed to determine scale satisfaction with the information provided. Results: (1) Both DT and PL pre-post changes were significantly positive (DT: M = 5.4, SD = 3.0 versus M = 3.6, SD = 2.8; t-test p< .000); (PL: M = 5.3, SD = 4.4 versus M = 3.7, SD = 4.3; t-test p< .000). Except for the INFO25 RECLESS scale (less information desired), lower scores are better. (2a.) Generally, high distress and problems reported (i.e., scores increase), guarantees lower information satisfaction. (2b.) With one exception, the quartile range for each scale was consistently small. (2c.) Score trajectories for both DT and PL quartiles over the scales were similar. Conclusions: Although data suggests current consultation processes are significantly effective, there is room for satisfaction improvement. (2a.) Providers who continue to give the DT and PL prior to a consult, must ensure information satisfaction to pre-consult DT and PL high scorers. (2b.) Similar quartile scores for each scale suggests that individually tailoring the consultation based on pre-consult DT or PL scores alone (without satisfaction improvement efforts) may have minimal benefits. (2c.) Consult satisfaction improvement efforts should focus on the following scales: INFOCD (information on CD/tape/video); RECMORE (more information wanted); INFOTHSE (other services); INFOHELP (things you can do to help yourself get well); INFODIFP (different places of care); INFOTREAT (treatments), and; INFODIS (the disease).
Metabolites as mediator for alleviating adverse effects in chemotherapy: A new finding from a recent study of Japanese traditional Kampo medicine, rikkunshito (RKT).
Authors: Suzuki Hiroyuki , Inoue Takuya , Takagi Hironori , Watanabe Masayuki , Ozaki Yuki , Muto Satoshi , Okabe Naoyuki , Hasegawa Takeo , Shio Yutaka , Minemura Hiroyuki , Kanazawa Kenya , Ohbuchi Katsuya , Fukushima Takahisa
Published: May 2019

e18292

Background: In Japan, RKT is used for chemotherapy-induced anorexia. There is considerable variation in the therapeutic response to RKT. We assessed the efficacy of RKT on anorexia induced by cisplatin (CDDP) therapy in lung cancer patients (pts) from the clinical and the plasma metabolomics perspectives. Methods: The study was a double-blind, randomized trial evaluating pts with age ≥20 y with lung cancer assigned to receive regimen including CDDP, ECOG PS 0 to 1. Pts were administered RKT or placebo from the beginning of 1st course of chemotherapy (Day1) until just before starting the 2nd course (21 or 28 consecutive days). The clinical endpoints were the change in mean dietary intake in hospital (MDIH), QOL and nutritional indices. Plasma samples were collected at Day1, Day7 and Day22 (22nd or 29th day) for metabolome analyses. Results: 60 pts were enrolled between Nov 2014 and Aug 2017. 29 were allocated to RKT and 31 to placebo. The ANCOVA estimate of treatment effect in MDIH (baseline adjusted RKT-Placebo difference) was not significant (-6.7; 95% C.I. -61.1 to 47.8). Regarding QOL, there was no significant results in changes of QLQ-C30 Global Health Status. Among the related subscales, Pain in Day22 in PPS analysis was the only significant item (-17.0; -29.7 to -4.2). Regarding QLQ-LC13 , Alopecia in Day22 was the only significant item (-21.3; -36.9 to -5.8). The changes in nutritional indices did not show any significant difference, either. In metabolome analysis, CDDP drastically influenced metabolites, such as essential amino acids. RKT did not significantly change them compared to the placebo. In contrast, the changes of acetylglycine and arabinose in plasma strongly correlated with those in dietary intake and pain only in the RKT. Conclusions: In this exploratory study, no significant difference was observed in the MDIH. Although, pain and alopecia observed in QOL were significantly improved in the RKT. Some plasma metabolites were found to correlate with improvement in dietary intake or QOL. This is the first suggestive evidence that the efficacy of RKT would be variable depend on the metabolic profile. Clinical trial information: JAPIC CTI-142747.
Evaluation of inpatient cancer rehabilitation by routine electronic patient-reported outcome measures (ePROM): Improvement of quality of life (QoL) and psychological distress.
Authors: Licht Thomas , Nickels Alain , Riedl David , Rumpold Gerhard , Holzner Bernhard
Published: May 2019

e18294

Background: Many cancer survivors suffer from psychological distress and poor QoL. Cancer rehabilitation is aimed at improving their condition but the benefit remains controversial, we have thus investigated the outcome. Methods: ePROM were routinely integrated into the inpatient program of a cancer rehabilitation center in Austria. Hospital Anxiety and Depression Scale (HADS) was used to assess distress, and EORTC QLQ-C30 questionnaire for analysis of cancer-related symptoms and functions. Patients answered questions via internet prior to admission (T0). This allowed for allocation of physical therapies and 4-8 psychological counseling sessions according to their needs. Following informed consent, the outcome was investigated likewise by the time of discharge after 3 weeks (T1). Data were analyzed with SPSS software using ANOVA repeated measures. Results: 4198 patients (age 59.2±11.7 yr; range 18-91 years; 61.5% female) participated between January 2015, and August 2018. HADS identified a marked reduction of anxiety and depression, with distress levels similar to the normal population by T1. QLQ-C30 revealed significant increases for global QoL; physical, social, emotional and role functions. All recorded symptoms were improved, in particular fatigue, pain and insomnia. Moreover, subgroup analyses confirmed improvement for 11 investigated entities. Of notice, decrease of anxiety was most prominent in survivors of breast, head/neck and lung cancer patients (p < 0.001). No significant differences were observed between a subgroup of 1122 elderly ( > 70 yr), and younger patients except for the physical function, which improved significantly in older patients (p = 0.003). Conclusions: Our study shows that inclusion of ePROM into inpatient cancer rehabilitation helps allocate therapies according to individual needs. This large series demonstrates significant reduction of psychological distress and improvement of all parameters of QoL. [Table: see text]
Artificial intelligence-based clinical decision-support system improves cancer treatment and patient satisfaction.
Authors: Wang Zuochao , Yu Zhonghe , Zhang Xuejing
Published: May 2019

e18303

Background: Traditional diagnostic model for cancer heavily relies on physicians and their teams’ knowledge. However, under this diagnostic model, patients’ source of information is quite limited. Cancer patients usually fill with negative emotion. Lack of knowledge to the disease and treatment options further leads to less confidence to their treatment outcome. Methods: In order to improve their faith in getting proper treatment and the hope for surviving the deadly disease, we has introduced an artificial intelligence based clinical decision-support system, the Watson for Oncology (WFO), since May-2018. WFO is developed by IBM, it assesses information from a patient’s medical record, evaluates medical evidence, and displays potential treatment options. Our oncologist can then apply their own expertise to identify the most appropriate treatment options. We have generated a new 7-step consultation system with the help of WFO. That include 1: introduce the WFO to patients, 2: patients express their demands and expectations, 3: the oncologist presents patient’s medical condition, 4: discussion with other members in the consultation team, 5: input patients’ information into WFO system and review treatment options, 6: discuss and finalize treatment options with patients, 7: feedbacks form patients after consultation. 70 patients who were hospitalized from May-2018 to Dec-2018 were divided into two groups, 50 patients volunteered to be assigned to the new 7-step consultation system and 20 patients stayed with the traditional diagnostic method to find them treatment options. All patients were followed up by questionnaire. Results: The results showed that patients in the 7-step consultation group presented significantly higher satisfaction rate towards treatment options, confidence level to their health care workers, and willingness to follow the treatment option when compared to patients in the traditional diagnostic group. Conclusions: The WFO assisted 7-step consultation system not only provides a more efficient way to find treatment options, but also improves patients’ understanding to their disease and possible side effects towards the treatment. Most importantly, patients build stronger confidence with their health care team and are willing to believe they will benefit from the treatment plans.
Patient satisfaction with oncology clinical decision support in South Korea.
Authors: Lee Kyounga , Lee Seon Heui , Preininger Anita , Shim JungHo , Jackson Gretchen
Published: May 2019

e18329

Background: Watson For Oncology (WFO) is an artificial intelligence (AI) tool that presents therapeutic options to oncologists and patients at 9 hospitals in Korea. The earliest user is Gachon University Gil Medical Center (GMC), where the tumor board (MDT) is fully integrated with WfO (MDT-WfO). GMC patients and oncologists may select one of the treatment choices presented by MDT-WfO or choose to follow recommendations of one or more oncologists at GMC augmented by WfO (non-MDT-WfO). This study is aimed at determining the satisfaction of patients who pursue shared decision-making through the MDT-WfO approach. Methods: Cancer patients enrolled in this IRB-approved study and treated at GMC between March and September of 2018 were surveyed. All patients rated satisfaction levels from 1-10 after treatment decision-making was completed, with 1 indicating the lowest level of satisfaction and 10 the highest. For each question, the average satisfaction score for patients in the MDT-WfO group was compared to the mean for patients in the non-MDT-WfO group, with a t-test for significance. Results: There were 9 cancer types treated at GMC from March through September of 2018. Of the of 290 patients enrolled in this study, 130 (44.8%) selected MDT-WfO and 160 (55.2%) did not. Overall, patients that interacted with MDT-WfO viewed GMT more positively (86.9%) after treatment decisions had been made than patients in the non-MDT-WfO group (71.3%).Although patients did not report significantly differing levels of satisfaction for most survey questions, there was a significant difference in terms of satisfaction with the explanation they received from the medical staff. Satisfaction level for this item was 9.52 with MDT-WfO and 9.22 points without ( p = 0.029). Conclusions: Patients reported greater satisfaction in the explanations they received in the MDT-WfO group, consistent with their more positive impression of GMT after treatment decisions were made. More studies are needed to determine if the increase in the level of satisfaction for this item is due to explanations from MDT unrelated or related to WfO. More studies on how WfO is used differently by the tumor board and individual oncologists may provide a unique perspective on how WfO is integrated into the MDT.
The ability of isolated fine needle aspiration of lymph nodes to provide complete diagnostic information without necessitating additional diagnostic procedures: A retrospective cohort study.
Authors: Tidwell Nathan , Barnett Taylor Leslie , Thrun Connor H , Graham Brendan C , Graham Lindsey Jean
Published: May 2019

e18341

Background: Diagnostic fine needle aspiration (FNA) of pathologically enlarged lymph nodes is a relatively safe, quick, and well-tolerated procedure that can be quickly analyzed to identify the presence of malignant cells. Though proven very useful to assess for the presence or absence of malignancy for staging purposes, the procedure’s ability to provide adequate tissue to appropriately diagnose a new malignancy and perform all necessary predictive and prognostic studies has not been explored. Methods: We retrospectively reviewed clinical records of patients who underwent FNA of a pathologically enlarged lymph node for the purpose of obtaining a tissue diagnosis at our institution between January 2010 and December 2015. We then assessed the percentage of patients that required a second diagnostic procedure independent of the FNA result. Procedures done for therapeutic purposes (such as resection) were not counted as a second procedure. We also collected data on the type of procedure used to obtain FNA, patient history of malignancy, and whether the diagnosis was benign or malignant. Results: We identified 594 FNA procedures that fit the study criteria. Of these, 277 (46.6%) required an additional diagnostic procedure. Among the 277 that required a second procedure, 237 (85.6%) were benign and 40 (14.4%) were malignant on primary FNA (P < 0.0001). Of the 237 benign FNAs that required a second procedure, 84 (35.5%) had the diagnosis changed to malignant after the second procedure (P < 0.001). There was no difference between procedure used to obtain the FNA (bronchoscopy, endoscopy, percutaneous) or patient age in the need for a second procedure. Conclusions: Though fine needle aspiration is a useful procedure for establishing the presence or absence of metastatic disease, our analysis suggests that the ability of the procedure to reliably diagnose or provide sufficient tissue for ancillary testing is limited. Nearly half of the patients in this study were subjected to the risks, cost, and diagnostic delay associated with a second procedure.
Perspectives and practices of oncology providers in addressing financial toxicity.
Authors: Ragavan Meera Vimala , Parikh Divya Ahuja , Patel Manali I.
Published: May 2019

e18342

Background: Few studies have evaluated the perspectives and clinical practices of oncology providers in regards to assisting patients with financial toxicity. Our study sought to assess providers’ attitudes regarding their role in addressing patients’ financial concerns, understand practice patterns in discussing cost of care, and obtain feedback on potential interventions to help address existing barriers. Methods: We developed an 18-question electronic, anonymous survey informed by an extensive literature search and piloted with three physicians with health services research experience. We emailed the survey to 75 attending physicians in Medical Oncology, Hematology, and Radiation Oncology, 117 advance practice practitioners (APPs) and 46 trainees. Responses during the study period 12/12/2018-1/31/2019 were analyzed. Results: A total of 71 (response rate of 30%) participants completed the survey, including 31 attending physicians, 28 APPs, and 12 trainees. Sixty-two percent of participants agreed that oncology providers should openly discuss cost of care with patients. There was wide variation in opinion around whether providers should offer the same treatment recommendations to all patients regardless of cost, with one third stating they agreed, one third stating they disagreed, and one third stating they were neutral. Sixty-one percent of participants did not use any cost-effectiveness tools in decision making. Sixty-three percent of respondents stated that a gap in knowledge of out of pocket costs was the number one barrier to helping patients avoid financial toxicity. The highest ranked intervention of those listed was a guide on available resources for patients with financial needs, voted for by 70% of respondents. Conclusions: Providers identified many barriers at our institution to discussing cost of care, including lack of transparency of out of pocket costs and lack of awareness of available resources. Providers were overwhelmingly interested in incorporating institutional resources and cost-effectiveness tools into their clinical practices. These findings can inform provider-level interventions to better address the financial burden patients face with their cancer care.
Efficacy of a stepped collaborative care intervention for comorbid cancer and depression: Health care utilization and costs.
Authors: Richards Geena , Steel Jennifer Lynne , Geller David A. , Billiar Timothy , Procopio Judith , Kucinski Barbara , Murphy Emily , Tsung Allan , Marsh Wallis , Antoni Michael , Vodovotz Yoram , Spring Michael , Pathak Ritambhara , Cheng Hannah , Sidleck Blake
Published: May 2019

e18348

Background: The aims of this study were to test the efficacy of a stepped collaborative care intervention for comorbid cancer and depression on outcomes including complication rates, health care utilization and costs. Methods: Patients diagnosed with cancer were enrolled in a randomized controlled trial testing the efficacy of a stepped collaborative care intervention. Patients were administered a battery of questionnaires prior to randomization. Rates and severity of surgical complications, health care utilization and costs were collected for a one-year period after randomization. Descriptive statistics, Chi-square analyses, and Ordered Restricted Inference analyses were performed. Results: Of the 100 patients, the mean age was 64.0 (SD = 10.3), the majority of the patients were male (51%), Caucasian (89%), diagnosed with hepatocellular or cholangiocarcinoma (47%) and stage III and IV (60%). For patients less than 75 years, patients randomized to the collaborative care intervention had lower rates of complications after surgery [Χ2= 5.45, P = 0.02]. We observed that 16% of patients randomized to the collaborative care intervention had complications versus 66.7% of the patients in the screening and referral arm. For patients who survived 6 months or less, those who were randomized to the collaborative care intervention had lower rates of 90-day readmissions than patients randomized to the screening and referral arm [Χ2= 4.0, P = 0.046]. The patients randomized to the collaborative care intervention did not have any readmissions while 2 patients in the screening and referral arm were readmitted. Patients randomized to the collaborative care intervention arm had lower median costs associated with the loss of workforce productivity ($2340 versus $3001; P = 0.07), hospital costs ($13,008 versus $21,109, P = 0.09), and cost per hospital registration ($1158 versus $2219, P = 0.07) when compared to the screening and referral arm. Conclusions: The stepped collaborative care intervention not only reduced depressive symptoms, but patients randomized to this intervention had lower complication rates, health care utilization, loss of work productivity, and hospital related costs. Clinical trial information: NCT02939755.
Social values and cancer funding priorities: Empirical evidence for cancer policy.
Authors: Denburg Avram
Published: May 2019

e18352

Background: Achieving value in health care requires knowledge of public values and priorities. To better understand public values for resource allocation on cancer care, we conducted a population-based stated preference survey with a nested randomized controlled moral reasoning intervention. Our objective was to generate evidence to inform economic evaluation and policymaking on cancer care priority-setting and payment reform in developed health systems. Methods: We conducted a population-based stated preference survey of societal views on the prioritization of health resources between children and adults, administered to a nationally representative sample (n = 1,556) of Canadian adults. Allocative preferences were elicited across a range of hypothetical treatment scenarios and scored on a visual analogue scale. Participants were randomized to a moral reasoning intervention (n = 773) or a control group (n = 783). Those randomized to the intervention group were exposed to a moral reasoning exercise prior to each choice task. The exercise presented participants with a list of ethical principles relevant to health care resource allocation and tasked them to select the top principles guiding their choice. The main outcomes were the difference in mean preference scores by group, scenario, and participant demographics. Results: Multiple regression analyses demonstrated a consistent aggregate preference by participants to allocate scarce health system resources to children. Exposure to the moral reasoning exercise weakened but did not eliminate allocative preference for children, as compared to control (difference 0.72, SE 0.14, p < 0.0001). Younger respondent age (-0.71, SE 0.14, p < 0.0001) and parenthood (-0.40, SE 0.11, p < 0.0002) were associated with greater preference for children. The top three principles guiding participants’ allocative decisions were treat equally (54.3-63.9%), relieve suffering (39.6-66.1%), and rescue those at risk of dying (37-40.8%). Conclusions: Our results demonstrate a significant preference by participants to allocate health care resources to children, but one attenuated by exposure to a range of ethical principles to guide decision-making. It also evinced strong support for humanitarian principles to guide health care resource allocation. Definitions of value in health care based primarily on the magnitude of clinical benefit and cost-effectiveness may exclude moral considerations that the public values.
Impact of solid tumor brain metastases on end-of-life healthcare utilization.
Authors: Ray Emily Miller , Dunham Lisette , Reeder-Hayes Katherine Elizabeth , Sanoff Hanna Kelly
Published: May 2019

e18373

Background: Patients with brain metastases (BMets) represent a subset of cancer patients who may experience high costs and frequent healthcare utilization. This study aims to assess whether patients with BMets have higher likelihood of low-value healthcare utilization at the end of life compared to other patients with metastatic cancer. Methods: Using the Cancer Information and Population Health Resource, linking North Carolina Medicare and Medicaid and cancer registry data, we conducted an observational cohort study of decedents with metastatic cancer with or without BMets. The cohorts included adults with melanoma, renal cell carcinoma, breast cancer, or lung cancer, diagnosed 2003 to 2014. Multivariate logistic regression, adjusting for demographics, cancer type, systemic treatment, comorbidity, frailty, and hospice use, was used to examine the impact of BMets on emergency department (ED) use, hospitalization, and intensive care (ICU) in the 30 days prior to death. Results: Relative to patients without BMets, patients with BMets were more likely to experience a hospitalization (12.9% vs 9%, p < 0.001), but experience no difference in ED or ICU use. In adjusted analyses, BMets patients receiving systemic treatment were particularly high risk for hospitalization (OR 1.823, CI 1.504, 2.209). Black race; receipt of systemic therapy near the end of life; and Charlson comorbidity score of 3+ confers increased risk of ED use, hospitalization, and ICU use (Table). Utilization did not vary by cancer type. Conclusions: Patients with BMets are high risk for hospitalization at the end of life. Further study is needed to determine if targeted health system interventions can decrease hospitalizations in this patient group. [Table: see text]
Health-related quality of life (HRQoL) in patients with advanced melanoma receiving immunotherapies across real-world clinical practice settings.
Authors: Joseph Richard Wayne , Liu Frank Xiaoqing , Shillington Alicia C. , Macahilig Cynthia , Diede Scott J. , Dave Vaidehi , Harshaw Qing , Saretsky Todd L , Pickard Alan S
Published: May 2019

e21004

Background: Pembrolizumab (PEMBRO) and combination ipilimumab + nivolumab (IPI+NIVO) are FDA-approved immunotherapies for advanced melanoma (AM). HRQoL was better maintained with PEMBRO vs IPI in KEYNOTE-006. CheckMate-067 reported no clinically meaningful HRQoL differences with IPI+NIVO vs IPI. As randomized trial data are lacking, we compared HRQoL outcomes in AM between PEMBRO and IPI+NIVO in real-world clinical settings. Methods: A prospective, observational study was conducted with sponsor blinded to sites, and sites blinded to sponsor; nine oncologists from 9 US academic centers and affiliated satellite clinics enrolled AM patients (pts) age ≥18 years initiating first-line PEMBRO or IPI+NIVO between June 2017 – March 2018. The European Organization for the Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ C30) and EQ-5D-5L were administered at baseline and weeks 6, 12, 18, and 24 following therapy. Least squared (LS) mean changes in HRQoL scores from baseline were compared using mixed-effects models for repeated measures, adjusting for baseline covariates. Results: A total of 225 PEMBRO and 187 IPI+NIVO pts were enrolled, with > 95% questionnaire completion rates through week 24. At baseline, PEMBRO pts were more likely > age 65 (49% vs 37%, p = .011), stage IV disease (92% vs 85%; p = .002), and higher comorbidity index (1.0 vs 0.6; p < .001) compared with IPI+NIVO pts. Adjusted EORTC global health status/quality of life (GHS) LS mean changes from baseline showed greater improvement with PEMBRO vs. IPI+NIVO at 12, 18 and 24 weeks. At week 24, PEMBRO pts achieved a 3.3-point improvement (95% CI = 0.8, 5.7) and IPI+NIVO pts had no significant change (1.0, 95% CI = -1.6, 3.5), with a LS mean difference of 2.3 points (p = .037; 95% CI = 0.14, 4.51). At week 24, the EQ-5D visual analogue scale increased 1.0 (95% CI, -1.2, 3.2) for PEMBRO vs IPI+NIVO which decreased 0.9 (95% CI = -3.2, 1.3), with a statistically significant LS mean difference of 2.0 (95% CI = 0.4, 3.9; p = .045). Conclusions: Results from 2 measures suggest HRQoL was maintained vs. baseline in both PEMBRO and IPI+NIVO pts, with a significant between-group difference favoring PEMBRO in GHS over 24 weeks.
Safety and interim results from a phase II, single-arm study of atezolizumab and bevacizumab in Merkel cell carcinoma (MCC).
Authors: Ferrarotto Renata , Mata Javier , Mott Frank , Bhosale Priya , Rubin M. Laura , Altan Mehmet , Dervin Shannon , Yun Cindy , Yao James C. , Halperin Daniel M.
Published: May 2019

e21006

Background: MCC is an aggressive neuroendocrine carcinoma of the skin. Avelumab (anti-PD-L1) was FDA approved for the treatment of metastatic MCC based on an overall response rate (ORR) of 32% in chemotherapy-refractory pts. In first line, responses to PD1/PD-L1 have been reported in 56-62% of pts. Atezolizumab (Atezo) targets PD-L1 and bevacizumab (bev) inhibits VEGF. Pre-clinical data suggests atezo + bev improves antigen-specific T-cell migration, and encouraging clinical activity of this regimen has been reported in renal cell and hepatocellular carcinoma. Here we report safety and interim results of atezo + bev in MCC. Methods: In this phase II single-arm study the efficacy and safety of atezo + bev was evaluated in pts with recurrent/metastatic PD-1/PD-L1-inhibitor naive MCC. Patients were treated with atezo 1200 mg + bev 15 mg/kg IV Q3W. Primary endpoint was ORR (RECIST 1.1) by blinded independent radiologist. Secondary endpoints included ORR by iRECIST, PFS, DOR, DCR, OS, and safety. Results: 11 pts enrolled. Median age was 70 (range:57-84), (7) 63% were male, and 7 (63%) had been treated with curative intent. Five (45%) pts had received platinum/etoposide (2 in the neo-adjuvant setting and 3 in first-line). Median follow-up is 9.7 months (range:2.8-15.9). Adverse events (AEs) that occurred in > 1 pt: hypertension (7), proteinuria (3), fatigue (2), peripheral edema (2), epistaxis (2), and transaminitis (2). Grade 3 AEs: hypertension (2), proteinuria (1), and auto-immune hepatitis (1); all manageable. Only 1 subject discontinued treatment due to toxicity (auto-immune hepatitis). There were no grade > 3 AEs. Objective response occurred in 7 (64%) pts, including 3 (27%) complete responses (CR). One partial response was unconfirmed (patient discontinued treatment after 1 dose of atezo/bev due to grade 3 hepatitis). 4 pts remain on treatment (1 pt with CR withdrew consent for further therapy and has not recurred). Median PFS is 6.3 months (95% CI:4.5-NA). Conclusions: Atezo + bev was well tolerated in MCC pts. Safety was consistent with that of the individual agents. Activity is encouraging with 64% ORR (27% CR rate) and mPFS of 6.3 months. Clinical trial information: NCT03074513.
A phase II study of capecitabine (Cape) or 5-fluorouracil (5-FU) with pegylated interferon alpha-2b (Peg-IFNA-2b) in unresectable/metastatic cutaneous squamous cell carcinoma (CSCC).
Authors: Muzaffar Jameel , Khushalani Nikhil I. , Russell Jeffery Scott , Parameswaran Janaki , Kirtane Kedar , De La Iglesia Janis , Slebos Robbert , Chung Christine H.
Published: May 2019

e21020

Background: Patients (pts) with unresectable/metastatic CSCC have a poor prognosis, and until recently had limited treatment options. Based on encouraging efficacy in case report series, we conducted a phase 2 trial to evaluate the efficacy of CAP or 5-FU in combination with Peg-IFNA-2b in advanced CSCC. Methods: Eligible pts with measurable unresectable/metastatic CSCC were treated with CAP (1000mg/m2 PO twice daily days 1-14) or 5-FU (800 mg/m2 IV days 1-4), and Peg-IFNA-2b (subcutaneously at 3ug/kg weekly) in a 21-day cycle for up to 9 cycles, intolerable toxicity or progression. The primary objective was to assess overall response rate (ORR) while secondary objectives were safety and survival. Exploratory correlative tissue immune markers were studied using multiplex immunohistochemistry (mIHC) on pre- and post-treatment optional tumor biopsies. Results: Poor accrual led to early study closure after enrolling 8 pts. All pts were male, median age was 73.5 yrs. The ORR was 25% (1 CR, 1 PR); 4 pts had SD, 1 with PD and 1 withdrew consent prior to first restaging. The pt with CR had previously progressed on anti-PD1 therapy; tissue mIHC from this pt showed an increase in CD8+ cells prior to starting trial therapy. Due to the low sample size the 6 and 12-month survival estimates for OS and PFS are the same, 87.5% and 50% for 6 and 12 months respectively. Grade ≥ 3 or higher toxicities included decreased WBC (n = 3), fatigue, failure to thrive, anemia (all n = 2), and neutropenia, dehydration, hand-foot syndrome (all n = 1). Dose reductions were frequently encountered. Conclusions: Combination CAP/5-FU plus Peg-IFNA-2b has activity in advanced CSCC but with considerable toxicity at studied doses. The small sample size precludes meaningful conclusions on efficacy, though the CR observed post-PD1 progression might warrant further investigation of this combination as a therapeutic strategy given the recent approval of cemiplimab in CSCC. Clinical trial information: NCT02218164.
Dendritic cell vaccination in metastatic uveal melanoma as compassionate treatment: Immunological and clinical responses.
Authors: Moreira Alvaro , Gross Stefanie , Uslu Ugur , Doerrie Jan , Kummer Mirko , Schliep Stefan , Sponagl Felix , Lischer Christopher , Erdmann Michael , Heinzerling Lucie , Schuler Gerold , Schuler-Thurner Beatrice
Published: May 2019

e21024

Background: Other than cutaneous melanoma, metastatic uveal melanoma (UM) is minimally responsive to checkpoint inhibitors. The prognosis remains very poor with mortality rates nearly unchanged over the last decades. The recently growing insight that immunotherapy significantly improves outcomes for cancer patients led to a re-emergence of vaccines including dendritic cell (DC) vaccines. Methods: We vaccinated an UM patient in a compassionate use setting and assessed the immunological and clinical responses. Based on this experience we performed individual compassionate treatments in other UM patients using DC loaded by peptide pulsing and/or mRNA transfection (autologous tumor RNA or RNA coding for tumor antigens). Results: The first patient was vaccinated in 2013 after a liver metastasis was resected and checkpoint blockade with ipilimumab was started. In 2014 the patient showed progression in the liver. We continued DC vaccination in shorter intervals and adapted antigen loading (with mRNA coding for an individual GNAQ driver mutation) accompanied by a further cycle of ipilimumab. Therapy resulted in complete remission of liver metastases, but the patient developed new skin metastases. Again the loading of DC was adapted (peptides of passenger mutations predicted after Next-Generation Sequencing) and infusions with pembrolizumab were started. Pathology from some regressing lesions showed a massive T cell infiltration and in parallel GNAQ mutation-specific T cells could be found in the patient’s blood. Skin metastases regressed and the patient is now free of detectable tumor after 65 months. Immune monitoring in the patient’s blood showed a vaccine-induced functional T cell response against the QNAQ-driver mutation. Three of other four patients are also still alive, one in complete remission under DC vaccination in combination with pembrolizumab, two of them showing measurable disease, and one deceased disease related after 28 months, resulting in a median OS of the five patients of 36.4 months. Immune monitoring in one of those patients showed a CD4+ and CD8+ INF-gamma T cell response against the autologous tumor RNA vaccine. No grade 3 or 4 toxicity occurred. Conclusions: The observed prolonged median OS and the fact that 2/5 patients remain disease-free is definitely encouraging. Vaccination immunotherapy with antigen-laden DC is a potential therapeutic option for patients with metastatic uveal melanoma. Combinations with checkpoint inhibitors proved promising, and should be further evaluated in clinical trials.