bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase II RCT of high-dose vitamin D supplementation and exercise for cancer treatment-induced bone loss in breast cancer patients on aromatase inhibitors.
Authors: Peppone Luke Joseph , Reschke Jennifer E , Janelsins Michelle Christine , Inglis Julia Ellen , Mustian Karen Michelle , Culakova Eva , Kleckner Amber , Kamen Charles Stewart , Lin Po-Ju , Dunne Richard Francis , Kleckner Ian , Huston Alissa , Shayne Michelle , Morrow Gary R.
Published: March 2020

11500

Background: Cancer-treatment-induced bone loss (CTIBL) is a side effect of aromatase inhibitors (AIs) and can result in osteoporotic fractures. Vitamin D (VITD) protects against postmenopausal bone loss but it is unclear if the recommended daily allowance (RDA: 600 IU/day) of VITD is sufficient to prevent CTIBL. This phase II RCT aimed to assess the feasibility, safety, and preliminary efficacy of high-dose VITD (with and without exercise) on bone mineral density (BMD) compared to the RDA. Methods: Non-metastatic breast cancer patients starting AIs with low VITD (<32 ng/ml) were randomized 1:1:1 into 3 arms: 1) placebo 2) high-dose VITD (50,000 IU/week) or 3) high-dose VITD + Exercise for Cancer Patients (EXCAP): a home-based, personalized walking and resistance band training program for 24 weeks. All subjects received the RDA of VITD 600 IU/day. Serum VITD and calcium levels were assessed at baseline, weeks 6, 12, 18, and 24. BMD was assessed at the hip via DXA at baseline and week 24. Results: Of the 116 subjects randomized (mean age = 60; 94% white; mean baseline VITD = 24.6 ng/mL), 90 provided fully evaluable data. Compliance (≥ 80% of instructed doses) exceeded 95% in all 3 arms with no between-group difference. ANCOVA showed significant differences between groups on final VITD levels (high-dose = 63.6 vs high-dose + EXCAP = 60.3 vs placebo = 32.0 ng/mL; p<0.001) without severe calcium toxicities, as indicated by final calcium level (high-dose = 9.4 vs high-dose + EXCAP = 9.5 vs placebo = 9.4 ng/mL; p = 0.78). The placebo group lost a significant amount of hip BMD (−1.7%; p < 0.01) while hip BMD was maintained in the high-dose (−0.1%; p = 0.77) and high-dose + EXCAP (−0.2%; p = 0.74) resulting in significant between-group differences for high-dose + EXCAP vs placebo (p = 0.04) and high-dose vs placebo (p = 0.05). Conclusions: This is one of the first studies to show our novel high-dose VITD intervention, with and without exercise, significantly reduced hip BMD loss in breast cancer patients on AIs. Moreover, high-dose VITD supplementation is safe and feasible in this population. A phase III RCT is needed to confirm these findings. Funding: K07CA168911. Clinical trial information: NCT01419730.
Candidate SNPs enhance prediction of cognitive impairment after blood or marrow transplantation (BMT) for hematologic malignancy (HM).
Authors: Sharafeldin Noha , Richman Joshua , Bosworth Alysia , Chen Yanjun , Singh Purnima , Patel Sunita K. , Wang Xuexia , Morse Emily , Mather Molly , Sun Can-Lan , Francisco Liton , Forman Stephen J. , Wong F. Lennie , Bhatia Smita
Published: March 2020

11520

Background: We tested the hypothesis that candidate genetic variants are associated with cognitive impairment in BMT recipients for HM, and that inclusion of genetic variants improves the performance of a risk prediction model that includes only clinical and demographic characteristics. Methods: We used standardized tests to assess cognitive function in 277 adult BMT recipients at City of Hope (COH). Global Deficit Score (GDS) ≥0.50 was used as indicator of cognitive impairment. Generalized estimating equation models and logic regression were used to identify single-SNP and gene-level associations with cognitive impairment post-BMT. Three risk prediction models were developed in the COH cohort using elastic net regression: Base Model (sociodemographics); Clinical Model (Base Model + clinical characteristics, therapeutic exposures and baseline cognitive reserve); Combined Model (Clinical + Genetic Model). The Genetic Model included significant SNPs in blood brain barrier, telomere homeostasis and DNA repair identified from single- and gene-level analyses. Models were validated in an independent cohort of long-term BMT survivors (BMTSS) with (n = 141) and without (n = 258) memory problems. Results: Training set (COH): The cohort included 58.5% males; 68.6% non-Hispanic whites; 46.6% allogeneic BMT recipients; median age at BMT: 51.6y. The mean area under the receiver operating characteristic curve (AUC) was: Base Model: 0.69 (95%CI: 0.63-0.75); Clinical Model: 0.77 (95%CI: 0.71-0.83); Combined Model: 0.89 (95%CI: 0.84-0.92). Test set (BMTSS): Median age at BMT was 45y; 53.5% were males; 88.4% non-Hispanic whites. Testing the models in BMTSS yielded mean AUC of 0.57 (95%CI: 0.49-0.63) in the Clinical Model and 0.72, (95%CI: 0.65-0.78) in the Combined Model. Conclusions: These findings provide evidence on the utility of a validated risk prediction tool that incorporates genetic factors that could identify BMT recipients at risk for cognitive impairment, providing opportunities for targeted interventions.
End-of-life care and immune checkpoint inhibitors.
Authors: O'Sullivan Hazel , Collins Dearbhaile , O'Mahony Deirdre , Power Derek , Bambury Richard , O'Reilly Seamus
Published: March 2020

11531

Background: In the era of cytotoxic chemotherapy, aggressive cancer treatment and hospitalization at the end of life (EOL) has been associated with a worse quality of death. Meanwhile, in the era of immunotherapy (IO), little is known of the impact of these novel agents on EOL care. The aim of this study was to evaluate the EOL care of metastatic cancer patients treated with immune checkpoint inhibitors. Methods: We conducted a retrospective analysis of patients prescribedPD1/L1 or CTLA-4 antibodies in Cork University Hospital (CUH) and Mercy University Hospital (MUH) between January 2013 to December 2018. Patients treated on a clinical trial were excluded. Results: We identified 224 patients treated with immune checkpoint inhibitors (outside of a clinical trial) in CUH and MUH over the described 6 year period. 108 of these patients were deceased, 102 electronic files were available for analysis. Of the 102 patients, 57 had metastatic melanoma, 33 non small cell lung cancer, 8 renal cell carcinoma, 4 had other advanced malignancies. 43% were female and 57% were male. 6% of patients had an ECOG performance status (PS) of 0 at diagnosis, 80% PS of 1 and 10% PS of 2. Median age at death was 62 years. 47 patients were treated with pembrolizumab, 26 nivolumab, 25 ipilimumab, 2 nivolumab/ipilimumab and 2 received atezolizumab. 29 patients received IO as first line treatment, 50 as second line, 17 as third line and 6 as fourth line. Median number of IO cycles received was 4 (range 1 - 41). Progression of disease (62%) and declining performance status (14%) were the most common reasons for discontinuation of IO treatment. 16 of the 102 patients received a further line of systemic therapy. Median time from last dose of IO to death was 57 days. 20 patients (20%) died within 30 days of last dose of IO. Of these 20 patients, the median number of cycles of IO received was 2 (range 1-7), 8 of these 20 patients received one cycle of IO only. 39 patients (38%) attended the ED in the last month of life. 47 (46%) patients had at least one hospital admission in the last month of life, the median hospital length of stay was 6 days (range 1-30) and 22 patients died in hospital. 94% of patients were referred to palliative care, the median time from palliative care referral to death was 64 days (range 1- 1010), 62% of patients died in hospice. Conclusions: Patients with advanced cancer treated with immunotherapy have high rates of hospital admissions and ED attendances despite early palliative care involvement. 20% of patients died within 30 days of IO. More research is needed to help physicians identify patients who are least likely to benefit from IO so as not to treat futile cases.
Immune checkpoint inhibitor use near the end of life.
Authors: Glisch Chad , Snyders Travis , Gilbertson-White Stephanie , Hagiwara Yuya , Milhem Mohammed M. , Lyckholm Laurel
Published: March 2020

11533

Background: Studies of chemotherapy near the end of life reveal increased costs, adverse effects and minimal clinical benefit. Immune Checkpoint Inhibitor (ICI) use near the end of life has not been described. We studied factors related to ICI use near the end of life. Methods: We conducted a single-institution retrospective chart review of patients who received ICI and died between August 2014 and December 2018. End of life ICI (EOL-ICI) was defined as treatment within the last 30 days of life and comparisons were made to patients who received treatment > 30 days from end of life (non EOL-ICI). Results: 441 patients were reviewed. Mean age was 64 and 182 (41%) were female. 294 (67%) received ICI within the last 90 days of life and 117 (27%) within the last 30 days of life. At time of last ICI, 145 (33%) had brain metastases and 416 (94%) were stage 4. The most common cancers were melanoma (124, 28%), NSCLC (118, 27%) and urothelial carcinoma (34, 8%). The EOL-ICI group had a higher proportion of patients with ECOG ≥3 at time of last treatment (22% vs. 7%, p = < .001), higher rate of death in hospital (32% vs. 18%, p = 0.003) and lower hospice enrollment (52% vs. 76%, p = < .001). The EOL-ICI group received fewer ICI doses (mean 5.1 vs 6.7, p = 0.016). A higher proportion of patients in the EOL-ICI group were just beginning treatment and received ≤ 3 doses (60% vs 40%, p < .001). There was no difference in mean age or presence of brain metastases between the groups. Even when the cutoff for EOL-ICI is extended from 30 to 90 days, there remain significant differences in ECOG, hospice enrollment and starting ICI but no difference in rate of dying in the hospital. Conclusions: One out of four patients studied received ICI within the last 30 days of life. EOL-ICI treatment is associated with higher rates of death in the hospital and lower hospice enrollment. Our results suggest that performance status is important when considering treatment with ICI. Use of ICI in the last 30 days of life had minimal clinical benefit and high cost.
Write to recover: The impact of group led creative writing on behavioral health outcomes in cancer patients.
Authors: Nesterova Darya , Zhu Junjia , Kramer Courtney , Vasekar Monali K. , Collins Jolene , Truica Cristina I. , Joshi Aditya , Hayes Michael , Saunders Erika , Drabick Joseph J. , Joshi Monika
Published: March 2020

11536

Background: The diagnosis of cancer can adversely affect mental wellbeing. In addition to treating cancer, the emotional wellbeing of patients must simultaneously be addressed. A previous pilot exploring the feasibility of creative writing workshop (CWW) in cancer patients showed apositive effect on patients’ mental health. Methods: To longitudinally evaluate the efficacy of CWW on mood, we conducted a phase II study with cancer patients (any stage, any cancer type); randomized 2:1 to CWW vs. active control (AC). Patients in the CWW arm attended at least 4, 1.5-hour bi-monthly CWW x 8 wks, whereas AC patients completed independent writing at home with the help of a book (bi-monthly x 8wks). We used validated tools, [Emotional Thermometer Scales (ETS), PHQ-9, GAD-7] to assess changes in overall mood, depression, and anxiety. Primary end point: a) ETS scores before and after intervention b) Changes in depression and anxiety based on PHQ-9 and GAD-7 scores. We present results from ETS scores. Descriptive statistics were generated for these quantitative scales measured in each group, pre and post intervention. Comparisons between groups (gp) were made using Wilcoxon Rank-sum tests. All tests were two sided and the statistical significance level used was 0.05. Results: Amongst evaluable patients, N of 50 (demographics in table below), twenty-six patients in the CWW gp attended at least one class and 19 attended at least 4 classes. Patients in CWW showed significant mood improvement vs. AC when comparing the final overall ETS (p=0.0063). Three of the five sub-scale ETS scores were significantly lower for the CWW vs. AC gp: anxiety (p=0.0027), depression (p=0.0009), and anger (p=0.0027). Conclusions: Group led CWW have a positive effect on mood. Our results suggest potential therapeutic benefit of this intervention on the emotional wellbeing of cancer patients. Larger studies are needed to evaluate the effect of CWW in cancer patients. Clinical trial information: NCT03536702. [Table: see text]
Functional impairment on admission and associated symptom burden and health outcomes among hospitalized patients with advanced cancer.
Authors: Lage Daniel E , El-Jawahri Areej , Fuh Charn-Xin , Newcomb Richard , Jackson Vicki , Greer Joseph , Temel Jennifer S. , Nipp Ryan David
Published: March 2020

11554

Background: Hospitalized patients with cancer often have impaired function, as measured by activities of daily living (ADLs), related to age, comorbidities, and both cancer and treatment-related morbidity. However, the relationship between functional impairment and patients’ symptom burden and clinical outcomes has not been well described. Methods: We prospectively enrolled patients with advanced cancer with unplanned hospitalizations at an academic medical center. Upon admission, nurses assessed patients’ ADLs (mobility, feeding, bathing, dressing, and grooming). We used the Edmonton Symptom Assessment Scale (ESAS) and Patient Health Questionnaire-4 to assess physical and psychological symptoms, comparing symptom burden between patients with and without ADL impairment. We used regression models adjusted for age, sex, education, Charlson comorbidity index, months since advanced cancer diagnosis, and cancer type to assess the relationship between any ADL impairment on admission and hospital length of stay, the composite outcome of death or readmission within 90 days of discharge, and survival. Results: Among 932 patients, 40.2% had at least one ADL impairment. Patients with ADL impairment were older (Mean = 67.2 vs 60.8 years, p < 0.001), had higher Charlson comorbidity index (Mean = 1.1 vs 0.7, p < 0.001), and higher physical symptom burden (ESAS Physical Mean = 35.2 vs 30.9, p < 0.001). Those with ADL impairment were more likely to have moderate to severe constipation (46.7% vs. 36.0%, p < 0.01), pain (74.9% vs. 63.1%, p < 0.01), drowsiness (76.6% vs. 68.3%, p < 0.01), as well as symptoms of depression (38.3% vs. 23.6%, p < 0.01) and anxiety (35.9% vs. 22.4%, p < 0.01). In adjusted models, ADL impairment was associated with longer hospital length of stay (B = 1.30, p < 0.01), higher odds of death or readmission within 90 days (odds ratio = 2.26, p < 0.01), and higher mortality (hazard ratio = 1.73, p < 0.01). Conclusions: Hospitalized patients with advanced cancer who have functional impairment experience a significantly higher symptom burden and worse health outcomes compared to those without functional impairment. These findings highlight the need to assess and address functional impairment among this population to enhance their quality of life and care.
Analysis of financial sustainability of survivorship clinics led by advanced practice providers.
Authors: Rodriguez Maria Alma , Palos Guadalupe R. , Gilmore Katherine Ramsey , Lewis-Patterson Paula A. , Chapman Patricia , Bi Weiqi
Published: March 2020

11560

Background: Disease specific Survivorship Care Clinics (SCs) have been established within a comprehensive cancer center. Clinics are staffed by Advanced Practice Providers (APPs), Physician Assistants and Advanced Practice Registered Nurses, with experience in the management of each disease type. To determine the sustainability of this model of survivorship care, we analyzed the professional fees’ revenue generated by APPs’ billings for 6 clinics and then compared the APPs’ salaries across all clinics. Methods: A retrospective analysis was conducted of 6 survivorship clinic’s patient volumes and clinic days supported by APPs from 9/1/16-4/30/17. The full FTE salary of the APPs, including benefits were prorated to the time dedicated to each of the SCs. Institutional financial data was used to align professional fees to actual reimbursements received. Salary recovery percentage was calculated as the ratio of reimbursement received to prorated FTE salary. Results: Table shows variation in APPs’ salary commensurate to FTE proportion. Results also indicate there was an average of 99% professional fee recovery. Clinics with an FTE proportion > 0.5 had recovery higher than the anticipated prorated salary, suggesting there is a threshold to maximize efficacy and sustainability. Conclusions: APPs professional fees for care provided to cancer survivors are reimbursable, across disease types or payers, and proportionally supports their salaries. Our findings suggest delivery models based on APPs to manage care of long-term survivors can be self-supporting.[Table: see text]
Return to work after breast cancer: Comprehensive longitudinal analyses of its determinants.
Authors: Dumas Agnes , Luis Ines Maria Vaz Duarte , Bovagnet Thomas , Di Meglio Antonio , El-Mouhebb Mayssam , Pinto Sandrine , Charles Cecile , Dauchy Sarah , Coutant Charles , Cottu Paul H. , Lesur Anne , Lerebours Florence , Tredan Olivier , Vanlemmens Laurence , Levy Christelle , Lemonnier Jerome , Mesleard Christel , Arveux Patrick , Andre Fabrice , Menvielle Gwenn
Published: March 2020

11564

Background: The interplay between breast cancer (BC) late effects, psychosocial and work-related factors in return to work (RTW) is not well understood. Previous reports were retrospective and did not combine all these features. Methods: We used data of a French prospective cohort study (CANTO, NCT01993498) of stage I-III BC patients (pts) including detailed clinical data of 1,874 pts working at diagnosis (dx) and ≥5 years younger than legal retirement age. The outcome was non-RTW 2 years after dx. Multivariable regressions were conducted to identify correlates of non-RTW. First, we examined the independent effect of treatments, toxicities (Common Toxicity Criteria Adverse Events), and patient reported outcomes (EORTC BR23 and FA12; Hospital Anxiety and Depression Scale) collected shortly after end of primary treatment. Then, in a restricted sample of 1,003 pts with working conditions (WC) information available, we fitted models to account for detailed pre-dx WC including type of contract, working hours, strenuous postures, supportive environment, degree of autonomy and perception of work. All models were adjusted for age, stage, marital status, socioeconomic status and comorbidities. Results: Two years after dx, 21% of pts did not work. Adjusted odds of non-RTW were increased among pts treated with combinations of chemotherapy (CT) and trastuzumab (TR) (e.g. OR of CT-TR = 2.20 [95% CI 1.24-3.88] and OR of CT-TR-hormonotherapy (HT) = 1.72 [1.13-2.63] vs. treated only with CT-HT), who had severe arm morbidity (OR = 1.73 [1.27-2.36] vs. no), severe emotional fatigue (OR = 1.55 [1.03-2.32] vs. no), anxiety (OR = 1.51 [1.02-2.23] vs. no), or depression (OR = 2.23 [1.27-3.94] vs no). In addition, we also found that the odds of non-RTW were increased among pts who had shift working hours (OR = 2.23 [1.32-3.76] vs. no), who did not work in a supportive environment before dx (OR = 2.24 [1.44-3.50] vs. supportive) and who perceived their job as boring (OR = 3.57 [1.71-7.46] vs. not boring). Conclusions: More than 1/5 of pts did not RTW 2 years after dx, with treatment (trastuzumab), clinical, psychological and work-related factors being associated with job reintegration. Multidisciplinary strategies are needed to support BC survivors.
Growth of palliative care (PC) in United States cancer centers: A national survey.
Authors: Hui David , De La Rosa Allison , Chen Joseph , Delgado-Guay Marvin , Heung Yvonne , Liu Diane D. , Hess Kenneth R. , Bruera Eduardo
Published: March 2020

11601

Background: Outpatient PC facilitates timely referral and improved outcomes for cancer patients. We examined the change in outpatient PC services at US cancer centers over the past decade. Methods: Between April and August 2018, we surveyed all 62 National Cancer Institute designated cancer centers (NCI-CCs) and a random sample of 61 out of 1306 non-NCI-CCs. Two surveys previously used in a national study (Hui et al. JAMA 2010) were sent to each institution: a 22-question executive survey inquired about PC infrastructure and attitudes toward PC and an 82-question PC program leader survey inquired about the PC structures, processes and outcomes in detail. Generalized linear mixed model and logistic regression were used to examine the change in availability of outpatient PC services between 2009 and 2018 among NCI-CCs and non-NCI-CCs, respectively. Results: Among NCI-CCs, 40/62 (65%) executives and 52/61 (85%) program leaders responded. Among non-NCI-CCs, 41/61 (67%) executives and 27/39 (69%) program leaders responded. For NCI-CCs, we observed a significant increase in outpatient PC clinic between 2009 and 2018 (59% v. 95%; OR 13.1, 95% CI 2.6-66.8; P = 0.004) but no significant change in inpatient consultation team (92% v. 90%), PC unit (26% v. 40), nor institute-run hospice (31% v. 18%). For non-NCI-CCs, there was a significant increase in outpatient PC clinics (22% v. 42%; OR 2.51, 95% CI 1.01, 6.26; P = 0.05) and decrease in institute-run hospice (42% v. 22%; P = 0.05) over the past decade but no significant change in inpatient consultation team (56% v. 68%) and PC unit (20% v. 17%). The median (IQR) duration from outpatient referral to death increased from 90 (84, 120) days to 180 (131, 220) days for NCI-CCs and from 41 (28, 54) days to 84 (48, 120) days for non-NCI-CCs, respectively. We also observed significant growth in staffing, service hours, number of referrals, fellowship programs and rotations for oncology fellows, although research activity remains low. Conclusions: Cancer centers reported significant growth in outpatient PC clinics and overall PC infrastructure since 2009. However, major gaps in structures and processes exist, such as the lack of outpatient clinics at non-NCI-CCs, absence of PC units and limited research.
The development of a nomogram to determine the risk for inappropriate opioid use in cancer patients.
Authors: Yennu Sriram J. , Dev Rony , Edwards Tonya , Arthur Joseph Anthony , Lu Zhanni , Erdogan Elif , Malik Jimi S. , Naqvi Syed M. , Wu Jimin , Liu Diane D. , Williams Janet L. , Hui David , Reddy Suresh , Bruera Eduardo
Published: March 2020

11602

Background: Non-Medical opioid use is a growing crisis. Cancer patients at risk of harmful use of prescribed opioids are frequently underdiagnosed. The aim was to develop a nomogram to predict the probability of occurrence of Inappropriate opioid use that is, presence of SOAPP ≥ 7) among patients receiving outpatient supportive care consultation at a comprehensive cancer center. Methods: 3588 consecutive cancer patients referred to a supportive care clinic from March 1, 2016 to July 15, 2018 were reviewed. Patients were eligible if they had diagnosis of cancer, and were on opioids for pain for at least a week. All patients were assessed using Edmonton Symptom Assessment Scale with spiritual pain and financial distress (ESAS-FS), MEDD (morphine equivalent daily dose), SOAPP-14 (validated questionnaire for assessment of risk of inappropriate opioid use, and CAGE-AID (screening questionnaire for alcoholism/substance use disorder). Patients at with SOAPP+ were defined by SOAPP score ≥7. A nomogram was devised based on the risk factors determined in the multivariate logistic regression model and it can be used to estimate the probability of inappropriate opioid use. Results: Median age was 62yrs. Median ESAS pain item score on consultation was 5, Median ECOG was 2.20.4% were SOAPP+ and 10.1% were CAGE-AID+. SOAPP+ was significantly associated with gender, race, marital status, smoking status, depression, anxiety, financial distress, MEDD and CAGE score. The C-index is 0.8(CI 0.78, 0.82). A nomogram was developed. For example, for a male Hispanic patient, who is married, never smoked, with the following ESAS scores: (depression = 3, anxiety = 3, financial distress = 8), CAGE score of 0, and MEDD of 20, the total score is 9+9+0+0+6+10+26+0+1 = 61. In the nomogram a score of 58 indicates the probability of inappropriate opioid use being 0.1 and a score of 88 indicates the probability of 0.2. Based on the patient’s total score of 61, the probability of his aberrant behavior is between 10% to 20% (close to 10%). Conclusions: A nomogram can predict the risk of inappropriate opioid use in cancer patients.
Effect on pain outcomes in patients treated for painful bone metastases with biopolar RFA: The OPuS One study.
Authors: Bagla Sandeep , Levy Jason , Hopkins Thomas ,   OPuS One Study Investigators
Published: March 2020

11605

Background: To report the preliminary outcomes from the prospective, nonrandomized, multicenter study of the OsteoCool Radiofrequency Ablation system used for the palliative treatment of patients with painful bone metastases (OPuS One Study). Methods: Subjects were prospectively enrolled (NCT03249584) from October 2017 through August 2018. Inclusion criteria were: 2 or less painful target sites involving the thoracolumbar spine, pelvis and/or sacrum, with a worst pain ≥4/10 measured by the Brief Pain Inventory (BPI) within the previous 24 hours. RFA was performed with the OsteoCool device (Medtronic) under imaging guidance and followed by cementoplasty at operator discretion. Subjects were evaluated prior to RFA, at discharge, 3 days, 1 week, and 1-, 3-, 6-, and 12-months. Demographics and disease characteristics were collected at baseline and outcomes were assessed using validated measures. Device-, procedure- and/or therapy-related adverse events (AEs) were collected. Results: At the time of the analysis, 37 subjects at 8 US centers underwent RFA. The mean age was 64 years (range 30-89) and 68% were female. Mean baseline BPI worst pain was 8.6. The most common histology was adenocarcinoma; breast (32%) and lung (24%) were reported as the most common primary cancer. Thirty-one subjects (84%) were treated for lesions involving the thoracolumbar spine, while 6 subjects (16%) were treated for lesions located the pelvis and/or sacrum. All RFA procedures were technically successful. Of the 14 subjects presenting at the 3-month visit, 93% did not undergo radiation therapy at the targeted site(s) between baseline and 3 months. Seventy-four percent (25/34) of subjects at 1 week and 93% (13/14) of subjects at 3 months reported a clinically significant change from baseline in worst pain of ≥ 2 points. One AE, drug hypersensitivity, resolved without intervention. All eleven deaths reported were attributed to the subjects underlying malignancy and not related to RFA. Conclusions: The preliminary results of the OPuS One study show rapid pain improvement at 1 week and sustained long-term relief through 3 months in patients with metastatic bone disease. Clinical trial information: NCT03249584.
Engaging care partners in breast cancer care and communication.
Authors: Aufill Jennifer , Wolff Jennifer L. , Echavarria Diane , Heughan JaAlah-Ai , Lee Kimberley T. , Bantug Elissa Thorner , Levy Howard , Dy Sydney M. , Wolff Antonio C.
Published: March 2020

11614

Background: Family is often overlooked in cancer care. Little is known about the patient preferences for involving family in communication, whether preferences may be elicited and supported at the point of care, and impact on care quality. Methods: We conducted a two-group pilot randomized controlled trial (NCT03283553) of patients on active treatment for breast cancer and the “care partner” who accompanies them to routine visits (n = 132 dyads). Intervention dyads (n = 69) completed a self-administered checklist to clarify the care partner role, establish a shared visit agenda, and facilitate access to the electronic health record (MyChart) patient portal. Control dyads (n = 63) received usual care. Intervention acceptability and short-term effects were assessed from post-visit surveys and MyChart utilization at 6 weeks. Results: At baseline, most patients (89.4%) but few care partners (1.5%) were registered for MyChart. Most patients (79.4%) wanted their care partner to have access to their records and 39.4% of care partners reported accessing it in the past year using the patient’s account login/password. In completing the checklist, intervention patients and care partners identified an active communication role for the care partner and similar issues for the visit agenda: topics most frequently selected were treatment goals/expectations (75.4% & 66.7%, respectively), symptoms/side effects (73.9% & 62.3%) and chances of cancer recurrence/spread (49.3% & 44.9%). More than 90% of intervention participants reported that completing the checklist was easy, useful, and recommended it to others. At 6 weeks, intervention (vs control) care partners were more likely to be registered for MyChart (75.4 % vs 1.6%; p < 0.001), to have logged in (43.5% vs 0%; p < 0.001) and viewed clinical visit notes (30.4% vs 0%; p < 0.001), but no more likely to have exchanged direct messages with the clinical team (1.5% vs 0%; p = 0.175). No difference in patient MyChart registration, use, or messaging was found at 6 weeks, but intervention patients more often viewed clinical visit notes (50.7% vs 9.5%; p < 0.001). Conclusions: A self-administered patient-family communication intervention affected online practices of patients and cancer care partners. Follow-up continues. Clinical trial information: NCT03283553.
A randomized phase II trial of CX-01 with standard therapy in elderly patients with acute myeloid leukemia (AML).
Authors: Kovacsovics Tibor , Levy Moshe Yair , Cook Rachel J. , Kolitz Jonathan E. , Westervelt Peter , Donnellan William Bruce , Stuart Robert K. , Reagan John Leonard , Tsai Michaela L. , Wieduwilt Matthew Joseph , Maris Michael B. , Stevens Don A. , Yang Jay , Arana-Yi Cecilia , Safah Hana , Marcus Stephen Garrett , Shami Paul J.
Published: March 2020

7001

Background: Elderly AML patients have poor outcomes irrespective of therapy. CX-01 is a low anticoagulant heparin derivative that retains heparin’s ability to alter the activity of the CXCL12/CXCR4 axis, P-selectin, extracellular histones, and Platelet Factor 4. A pilot study of CX-01 combined with standard therapy for AML led to a complete remission (CR) rate of 92% ( Blood Adv 2:381, 2018). We conducted a randomized, dose-finding study of the same combination in newly diagnosed elderly AML patients. Methods: 76 fit patients older than 59 were randomized to induction with idarubicin and cytarabine on a 7+3 schedule only (Group 1); 7+3 with a lower dose of CX-01 (0.125 mg/kg/hour) (Group 2); or 7+3 with a higher dose of CX-01 (0.25 mg/kg/hour) (Group 3). Patients in CR received consolidation therapy consisting of up to 3 cycles of intermediate dose cytarabine (1000 mg/m2 every 12 hours on Days 1, 3, 5) without or with the same dose of CX-01 for Groups 1, 2, and 3, respectively. CX-01 was given as a continuous infusion after a 4 mg/kg bolus until completion of chemotherapy. Results: 66 of 75 treated patients were evaluable for response. Ten patients were not evaluable due to withdrawal of consent (6 patients), introduction of midostaurin after its approval (3 patients), or death due to hepatic sinusoidal obstructive disease at Day 21 (1 patient in Group 2). We present results for evaluable patients and not on an intent to treat basis. Baseline characteristics were similar across groups. The composite CR rate (CR + CRi) was highest for patients in Group 3 with 89% patients achieving a composite CR as compared to 58% and 50% in Groups 1 and 2, respectively. Kaplan-Meier curves indicated a statistically significant improvement in event free survival (EFS) (P = 0.019) and a non-significant trend (P = 0.10) to improvement in OS in Group 3 as compared to Group 1. Groups 1 and 2 were comparable for EFS and OS. CX-01 was well tolerated without increased incidence of bleeding in Groups 2 and 3. Conclusions: The encouraging CR rate and EFS in elderly fit patients with newly diagnosed AML suggests that CX-01 may potentiate the efficacy of standard AML induction therapy. A randomized study to confirm these findings with the higher dose of CX-01 is warranted. Clinical trial information: NCT02873338.
Randomized phase II study of cladribine with simultaneous or delayed rituximab in patients with untreated hairy cell leukemia.
Authors: Chihara Dai , Arons Evgeny , Stetler-Stevenson Maryalice , Yuan Constance , Zhou Hong , Raffeld Mark , Xi Liqiang , Steinberg Seth M. , Wisch Laura , Feurtado Julie , James-Echenique Lacey , Braylan Raul , Calvo Katherine R. , Maric Irina , Dulau Alina , Kreitman Robert J.
Published: March 2020

7003

Background: Single-agent purine analog therapy, usually cladribine, has been the standard 1st-line therapy of hairy cell leukemia (HCL) for ~30 years. Relapse is attributed to minimal residual disease (MRD) persisting despite complete remission (CR). Rituximab can clear MRD, but there are no long-term data for how frequently and for how long this happens, or even how frequently MRD remains after cladribine. We therefore conducted a randomized phase II trial of 1st-line cladribine with concurrent vs delayed rituximab. Methods: The primary endpoint was to determine if 8 weekly doses of rituximab (375 mg/m2 iv) begun the same day as 5 daily doses of cladribine (0.15 mg/kg iv) reduce HCL MRD 6 months later compared to cladribine alone. Secondary endpoints included testing delayed rituximab, 8 weekly doses beginning if/when MRD is detected in blood (or if HCL-related cytopenias persist preventing consideration of CR) ≥ 6 months after cladribine. Both groups could receive a 2nd course of rituximab if the same situation recurred ≥ 6 months after starting the 1st course of rituximab. MRD was assessed in blood (PB) and bone marrow (BM) using flow cytometry (FC), consensus PCR, and immunohistochemistry. Results: Sixty-eight patients were randomized 1:1 to concurrent vs delayed arms. At 6 months after cladribine, 97% concurrent vs 24% delayed (p < 0.0001) patients were MRD-free by all tests. 100% concurrent vs 41% delayed patients were MRD-free by all tests except BMA FC (p < 0.0001). At a median follow-up of 87.3 months, delayed rituximab was required by 1 concurrent patient vs 27 courses in 21 delayed patients. MRD-free survival after 1st rituximab was not reached for 34 patients after concurrent rituximab, with 32 still MRD-free after a median of 72 months (94% MRD-free survival), compared to median MRD-free survival 60.1 months after delayed rituximab, with 10 (48%) of 21 remaining MRD-free (p < 0.0001, hazard ratio for concurrent rituximab 0.09). Conclusions: Achievement of MRD-free CR after 1st line cladribine for HCL is greatly enhanced by concurrent rituximab. Use of delayed rather than concurrent rituximab could achieve MRD-free CR but durability was clearly inferior to concurrent rituximab. Longer follow-up will determine if MRD-free survival leads to cures of HCL, increased CR duration, and/or less need for additional therapy. Clinical trial information: NCT00923013.
Frontline flumatinib versus imatinib in patients with chronic myeloid leukemia in chronic phase: Results from the China randomized phase III study.
Authors: Li Zhang , Meng Li , Zhang Yanli , Zhu Huanling , Cui Jiuwei , Sun Aining , Hu Yu , Jin Jie , Jiang Hao , Zhang Xi , Li Yan , Liu Qifa , Liu Li , Zhang Wanggang , Gu Jian , Qiao Jian-Hui , Liu Bingcheng , Zhang Fengkui , Guo Yong , Wang Jianxiang
Published: March 2020

7004

Background: Flumatinib (FM), a derivative of imatinib (IM), is a novel BCR-ABL1 tyrosine kinase inhibitor (TKI). The aim of this open-label phase III study was to validate the efficacy and safety of FM in comparison with IM as frontline treatment in Chinese patients with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CML-CP). Methods: Randomization was stratified by Sokal score with a 1:1 allocation to each arm. Primary endpoints were major molecular response (MMR = BCR-ABL IS≤0.1%) rates at 6 and 12 months. Molecular responses were assessed at a central laboratory blinded to treatment allocations during the study. Efficacy endpoints were analyzed for the intention-to-treat populations. This study is registered with ClinicalTrials.gov, number NCT02204644. Results: 400 eligible patients were randomized and patient characteristics at baseline were similar in each arm. The full analysis set (FAS) consisted of 393 patients who received FM 600 mg (n = 196) or IM 400 mg (n = 197) tablets once daily. Compared with IM, FM resulted significantly higher induction of MMR rate (%; 95%CI) at 6 month (33.7; 27.06-40.29 vs 18.3; 12.88-23.67; P = 0.0005) and 12 month (48.5; 41.47-55.47 vs 33.0; 26.43-39.56; P = 0.0021) and also at 3 month (8.2; 4.33- 12.00 vs 2.0; 0.06-4.00; P = 0.0058). Significantly more patients in the FM than in the IM arm achieved a complete molecular response (BCR-ABL IS≤0.0032%) at 12 months. Early molecular response (BCR-ABL IS ≤ 10%) at 3 months and early CCyR at 6 months were also significantly higher with FM than IM (82.1; 76.78-87.50 vs 53.3; 46.33-60.27; P < 0.0001 and 60.71; 53.88-67.55 vs 49.75, 42.76, 56.73; P = 0.0332). FM has a safety profile similar to IM. The rates of grade 3/4 TEAEs of FM were similar to IM, 56.57% (112 of 198) vs 41.38% (87 of 196). However, the frequencies of some nonhematological and hematological adverse events were significantly lower in the FM than in the IM arm, such as rash (4.59% vs 12.63%, P = 0.0064) and eyelid edema (0.51 vs 14.65, P < 0.0001); leukopenia (30.61 vs 62.63, P < 0.0001) and neutropenia (30.10 vs 59.60, P < 0.0001). No specific TEAE was identified in each arm. Conclusions: This phase III study met its primary endpoints. Our study results suggest that FM is comparable to IM in its safety and superior in its efficacy profile at 3, 6 and 12 month time points. These results support FM as a frontline treatment option for patients with newly diagnosed CML-CP. Clinical trial information: NCT02204644.
Correlation of BRAF V600E mutation with cardiac involvement assessed by heart imaging in a monocentric series of 205 patients with Erdheim-Chester disease.
Authors: Bravetti Marine , Azoulay Levi-Dan , Cohen-Aubart Fleur , Emile Jean-François , Amoura Zahir , Cluzel Philippe , Haroche Julien
Published: March 2020

7019

Background: Erdheim–Chester disease (ECD), an inflammatory myeloid neoplasm, is an histiocytosis associated with multisystem infiltration. Cardiovascular involvement in ECD is under-diagnosed and associated with poor outcome. The targetable BRAFV600Emutation is present in up to 70% of all ECD. Methods: Retrospective study of 205 patients (pts) with ECD who had cardiac imaging (195 MRI, 10 CT when MRI was contraindicated). We identified the types of lesions (infiltration, tumor, and effusion), localization (pericardial, myocardial, valvular) and consequences on cardiac function (coronary stenosis, atrial wall dyskinesia, diastolic and systolic functions). Results: 141 (68.8%) pts were male. 30 (14.6%) had mixed histiocytosis (mainly ECD + langerhans cell histiocytosis). BRAF mutation ( BRAFm) was found in 112 (54.6%) cases, while 59 pts (28.8%) were Wild Type (WT) and 34 pts (7.6%) had unknown BRAF status. Among the 205 cardiac imaging, 101 (49.3%) were abnormal. Cardiac involvement was found in 93 pts (49%). Among these, 72 had an impairment of the right ventricular atrioventricular sulcus (74%), 65 of the right atrium (RA) enclosure (69%). Alteration of Tricuspid Annular Plane Systolic Excursion was found in 15% and correlated with the size of the tumor. Pericardial involvement (effusion, thickening or contrast enhancement) was found in 59 pts (29%). Among BRAFm pts, 75 (67%) had a heart abnormality while 37 (33%) had normal imaging; Among WT pts 14 (23.7%) showed heart abnormality, whereas 45 (76.3%) had normal imaging (RR 2.8 (CI: 1.8-4.5); p = 1.8*10-7). A RA tumor was present in 51 (45.5%) BRAFm but only 6 (10.2%) WT pts respectively (RR 4.5 (CI : 2.0-9.8); p = 7*10-6). BRAFm was also associated with aortic infiltration (RR 1.76 (CI: 1.2–2.5)) and pericardial involvement (RR 2.12 (CI: 1.1–3.9), p = 0.0017). Conclusions: Cardiac infiltration is frequent in ECD (49.3%), especially RA tumor. BRAFm is associated with RA, aortic and pericardial involvements.
Time from randomization to first subsequent induction/salvage therapy (ST) in patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) treated with inotuzumab ozogamicin (InO) in the phase 3 INO-VATE trial.
Authors: Jabbour Elias , Stelljes Matthias , Advani Anjali S. , DeAngelo Daniel J. , Wang Tao , Neuhof Alexander , Vandendries Erik , Kantarjian Hagop M.
Published: March 2020

7025

Background: Additional salvage regimens are burdensome for R/R ALL patients (pts) due to therapy-associated toxicities, which may affect quality of life with poor efficacy. In INO-VATE (Kantarjian et al, NEJM 2016), pts receiving InO vs standard chemotherapy (SC) had significantly greater remission rates and longer overall survival; after study treatment discontinuation, overall fewer STs (mainly burdensome chemotherapies) were used in the InO group vs SC. Methods: Study design was published. Adults with CD22+ ALL who were due to receive 1st or 2nd salvage treatment were randomized 1:1 to InO (n = 164) or SC (n = 162). Time to the first ST (TST) was time from randomization to the start of the first ST. Pts who did not receive any ST were censored. Data cutoff: Jan 4, 2017. Results: Fewer InO pts had ST vs SC pts (Table). Among the censored pts, 83/108 (76.9%) in the InO vs 54/69 (78.3%) in the SC group died, 23/108 (21.3%) vs 5/69 (7.2%) were alive at the end of the study, and 2/108 (1.9%) vs 10/69 (14.5%) were no longer being followed for survival. TST was longer in pts receiving InO vs SC. Overall median (95% CI) TST was 18.8 (14.7–NA) vs 3.9 (2.4–5.1) months; hazard ratio (HR) = 0.34, 97.5% CI: 0.23–0.49, 1-sided P< 0.0001. For pts (InO: 85, SC: 126) who never received hematopoietic stem cell transplantation (HSCT) on study, fewer InO pts had ST vs SC pts; TST was significantly longer in InO vs SC. For pts (InO: 70, SC: 18) who had HSCT directly after salvage, TST was extended in InO vs SC. Conclusions: In this study, treatment with InO provided the benefit of extended TST, effectively allowing patients a longer time period until an ST was needed in both patients who proceeded to as well as those who did not proceed to HSCT. Clinical trial information: NCT01564784. [Table: see text]
Nonclinical safety assessment of AMG 553, an investigational anti-FLT3 CAR-T therapy.
Authors: Karbowski Christine M , Goldstein Rebecca , Frank Brendon , Kim Kei , Li Chi-Ming , Gibson Bradford , Homann Oliver , Hensley Kelly , Brooks Ben , Yan Qinghong , Hernandez Rocio , Adams Gregor , Boyle Michael C , Arvedson Tara Lynn , Lebrec Herve
Published: March 2020

7032

Background: FMS-like tyrosine kinase 3 (FLT3) is a tyrosine-protein kinase involved in hematopoiesis. In acute myeloid leukemia (AML), higher FLT3 transcript levels, independent of the presence of FLT3 mutations, correlate with higher leukocyte counts and higher degrees of bone marrow infiltration by leukemic cells. FLT3 protein is detectable on the cell surface of more than 80% of leukemia isolates from adult AML patients whereas FLT3 mutations are present only in approximately one third of patients. AMG 553 is a novel, investigational, adoptive cellular immunotherapy for the treatment of relapsed refractory AML, consisting of autologous T cells genetically modified ex vivo to express a transmembrane chimeric antigen receptor (CAR) to target FLT3 protein on the surface of AML cells irrespective of FLT3 mutational status. Methods: The nonclinical safety evaluation of AMG 553 includes assessment of FLT3 expression in normal tissues; in vitro assessment of cytotoxicity against human cells with or without FLT3 expression; toxicology studies in cynomolgus monkeys administered autologous T-cells transduced with an anti-FLT3 CAR or administered anti-FLT3 bi-specific T-cell engager (BiTE) antibodies. Results: Assessment of FLT3 expression in normal tissues indicates that FLT3 protein is detected on the cell surface of a subpopulation of human bone marrow hematopoietic stem and progenitor cells; expression in other tissues is cytoplasmic and not anticipated to be accessible to AMG 553. AMG 553-induced cytotoxicity was only observed in a percentage of primary bone marrow CD34+ cells. There was no evidence of CAR-T cell-mediated toxicity, expansion, or persistence in cynomolgus monkeys likely due to restricted cell surface FLT3 protein expression in healthy animals which demonstrates the limited value of such studies for this target. All findings in toxicology studies with anti-FLT3 BiTEs were consistent with the targeted killing of cells expressing FLT3 on the plasma membrane. Conclusions: The nonclinical safety data support AMG 553 as a novel therapeutic to target FLT3 protein on AML cells irrespective of FLT3 mutational status, while only affecting a percentage of normal hematopoietic stem and progenitor cells.
Phase II trial of CPX-351 (cytarabine:daunorubicin) liposome injection in patients with acute myeloid leukemia >60 years of age who have not been treated with intensive chemotherapy.
Authors: Ritchie Ellen K. , Lee Sangmin , Desai Pinkal M. , Ball Jeff , Samuel Michael S. , Curcio Tania , Miah Sumaiya , Roboz Gail J.
Published: March 2020

7044

Background: This study enrolled older patients without age limitation to intensive chemotherapy with CPX 351 allowing for prior treatment with low intensity regimens for MDS or AML. Methods: 30 patients aged ≥65yrs with diagnosed AML received up to two induction cycles and consolidation cycles of CPX-351 as a first intensive therapy. The primary efficacy endpoint was overall survival and the primary safety endpoint was 30-day mortality. Secondary efficacy endpoints included response rate and duration, and assessment of the relationship between cognitive function and treatment outcome. Although the primary efficacy endpoint data is pending, these interim results describe promising primary safety and efficacy endpoint results. Of the 30 patients enrolled, 10 patients (33.3%) were ≥75yrs old, 13 patients (43.3%) had had previous hematologic malignancies, 17 patients (56.6%) had adverse ELN risk stratification, and 16 patients (53.3%) had failed to respond to previous non-intensive treatments. In addition, all patients had an average of 2.1 co-morbid medical conditions. Results: 14 patients (47%) achieved best response criteria, with 12 patients (40.0%) achieving complete remission (CR) and 2 patients (6.6%) achieving complete remission with incomplete platelet or neutrophil recovery (CRi). 6 patients (20%) had a morphologic leukemia free state with pancytopenia and 10 patients had persistent disease. 8 patients (26.6%) went to stem cell transplant. 2 patients (6.6%) died within 30-days. Although final analysis on adverse events data is pending, 6 patients (20%) experienced a Grade 2 decrease in left ventricular ejection fraction (LVEF) at the end of first induction. Conclusions: These results suggest that in elderly AML patients regardless of age and prior treatment with non-intensive chemotherapy can be treated safely with CPX 351 with low 30 day mortality. CR in these patients is 40% with 26% going forward to stem cell transplant. Complete data will be assessed for OS and rate of MRD positivity. The relationship of cognitive and social factors to outcome will also be addressed.