bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurocognitive outcomes in adult survivors of neuroblastoma: A report from the Childhood Cancer Survivor Study.
Authors: Hesko Caroline , Liu Wei , Srivastava Deokumar , Brinkman Tara M. , Diller Lisa , Gibson Todd M. , Oeffinger Kevin C. , Leisenring Wendy , Howell Rebecca M. , Armstrong Gregory T. , Krull Kevin R. , Henderson Tara O.
Published: March 2020

11563

Background: Long-term survivors of neuroblastoma may be at risk for neurocognitive impairment due to young age at diagnosis and intensive multimodal therapies. Methods: 837 survivors of neuroblastoma (57% female; median [range] age 25 [17-58] years, age at diagnosis 1 [0-21] years) and 728 siblings (56% female; age 32[16-43] years) self-reported neurocognitive problems using a neurocognitive questionnaire. Impairment was defined as scores ≥90th percentile of siblings in emotional regulation (ER), organization, task efficiency (TE), and memory. Multivariable log-binomial models evaluated associations with treatment exposures, era and chronic conditions (Grade 2-4 CTCAE v5) adjusting for sex, age, and race. Analyses were stratified by age at diagnosis (≤1 and > 1 year) as proxy for risk group. Results: Rates of impairment were 19.7% (ER), 25.3% organization, 21.9% TE and 19.4% for memory. Survivors had 50% higher risk of impaired TE (≤1 year relative risk [RR] 1.48, 95% confidence interval [CI] 1.08-2.03; > 1 year: RR 1.58, CI 1.22-2.06) and ER (≤1 year RR 1.51, CI 1.07-2.12; > 1 year RR 1.44, CI 1.06-1.95) versussiblings. Among survivors ≤1 year at diagnosis, treatment with platinum (RR 1.74, CI 1.01-2.97), hearing loss (RR 1.95, CI 1.26-3.00), cardiovascular (RR 1.83, CI 1.15-2.89) and neurologic (RR 2.00, CI 1.32-3.03) conditions were associated with higher risk of impaired TE. Female sex (RR = 1.54, CI, 1.02-2.33), cardiovascular (RR 1.71, CI 1.08-2.70) and respiratory (RR 1.99, CI 1.14-3.49) conditions were associated with higher risk of impaired ER. Among survivors > 1 year at diagnosis those treated in 1970-79 vs. 1990-99 had 80% higher risk of impaired ER (RR 1.77, CI 1.02-3.06). Hearing loss (RR 1.56 (1.09-2.24), respiratory (RR 2.35, CI 1.60-3.45) and cardiovascular (RR 1.74, CI 1.12-2.69) conditions were associated with higher risk of impaired TE. Conclusions: Adult survivors of neuroblastoma are at-risk for neurocognitive impairment. Differences associated with age at diagnosis, chronic disease and treatment exposures may inform risk-stratified inventions to improve neurocognitive outcomes. Reduced risk in later eras may reflect improved supportive care and knowledge of late effects.
Polypharmacy risk among five-year cancer survivors.
Authors: Hsu Christine D. , Lund Jennifer Leigh , Nichols Hazel
Published: March 2020

11565

Background: Cancer survivors are increasing in the United States. Survivors often face cancer sequelae and side effects from treatment, which can arise during treatment or even months or years later. Survivors may therefore experience greater medication burden than the general population, increasing concerns for polypharmacy and risk of drug interactions and non-adherence. The objective of this study is to characterize prevalence of polypharmacy by cancer history in a nationally-representative sample of U.S. adults. Methods: Using National Health and Nutrition Examination Survey (NHANES) data from 2003-2014, we identified 32,330 individuals 20 years or older, 1,672 of whom had been diagnosed with cancer (excluding non-melanoma skin) at least five years before the survey. The association between cancer history and polypharmacy (5+ medications) was examined using Poisson regression models to calculate multivariable risk ratio (RRs) and 95% confidence intervals (CIs), adjusted for education, ethnicity, marital status, and age at survey. Results: Among five-year cancer survivors, 35% had a diagnosis within 5-9 years of the survey year, 26% within 10-14 years, 13% within 15-19 years, and 26% had a diagnosis 20 or more years before the survey year. Breast cancer was the most common type of cancer (23%), followed by cervical cancer (18%), prostate cancer (12%), and colon cancer (7%). Prevalence of polypharmacy was higher in cancer survivors (33.6%; 95% CI: 30.7-36.6%) than in those with no cancer history (13.0%, 95% CI: 12.4-13.7%) (RR: 1.32, 95% CI: 1.20, 1.45). Polypharmacy prevalence differed by age group (4.83% in 20-39 year olds; 40.37% in 40-64 year olds; 54.8% in 65 years and older), and within each age group, risk of polypharmacy was higher in cancer survivors than in those with no cancer history, with the most pronounced difference in cancer survivors 20-39 years old (RR: 2.93, 95% CI: 1.69-5.09), followed by 40-64 year olds (RR: 1.52, 95% CI 1.27-1.83) and those 65 years and older (RR: 1.17, 95% CI: 1.07-1.29). Conclusions: Cancer survivors are more likely to experience polypharmacy burden than those with no cancer history. Findings from this study can increase awareness about the unique challenges cancer survivors face and encourage medication reconciliation services.
Effect of race/ethnicity on long-term cytopenias and major infections in adolescent young adult breast cancer survivors.
Authors: Sauder Candice , Goldfarb Melanie , Gingrich Alicia , Li Qian , Wun Theodore , Keegan Theresa
Published: March 2020

11568

Background: Many Adolescent and Young Adult (AYA) Breast Cancer (BC) patients receive chemotherapy as part of their initial treatment. Long-term bone marrow suppression is a potential complication, but no studies have evaluated the impact of race/ethnicity on the development in AYA BC survivors. Methods: Female patients ages 15-39 diagnosed with BC during 1996-2012 and surviving ≥ 2 years were obtained from the California Cancer Registry and linked to statewide hospitalization data. We estimated the cumulative incidence of developing anemia, leukopenia, or major infection/sepsis (≥ 2 years after diagnosis), accounting for death as a competing risk, and examined the impact of race/ethnicity using multivariable Cox proportional hazards regression. Results: Of 14,729 patients, 48.8% were non-Hispanic white, 8.3% non-Hispanic black, 25.5% Hispanic, and 16.5% Asian/Pacific Islander. At diagnosis, 95.5% had local or regional disease (27.7% stage I, 49.4% stage II), and were mostly treated with surgery (96.2%) and chemotherapy (74.3%). The 10-year cumulative incidence of anemia (16.8% vs 11.7%), leukopenia (4.6% vs 2.1%), and major infection/sepsis (13.2% vs 7.9%) was greater following initial treatment with chemotherapy (p < 0.0001 for all vs no chemotherapy). In multivariable analyses controlling for sociodemographic factors, baseline comorbidities, treatment and stage, Blacks had the highest risk (vs. non-Hispanic whites) of medical late effects, including anemia [HR: 1.62, CI 1.41-1.86], leukopenia (HR: 1.53, CI 1.17-2.00), and major infection/sepsis (HR: 1.36, CI 1.16-1.60). Similarly, Hispanic and Asian/Pacific Islanders had a higher risk of developing anemia (HR: 1.16, CI 1.04-1.29; HR: 1.17, CI 1.03-1.33) and trended toward developing more leukopenia (HR: 1.24, CI 1.00-1.54; HR: 1.25, CI 0.98-1.61). Conclusions: AYAs of Black, Hispanic, and Asian/Pacific Islander race/ethnicity are at an increased risk of anemia and leukopenia after chemotherapy compared with non-Hispanic Whites. With improvements in prognostic testing resulting in potential decreased chemotherapy usage, there may be a decrease in long-term late effects for these young cancer survivors.
Total body irradiation (TBI) and risk of breast subsequent malignant neoplasm (SMN) after blood or marrow transplantation (BMT): A report from the BMT survivor study (BMTSS).
Authors: McDonald Andrew Michael , Chen Yanjun , Wu Jessica , Hageman Lindsey , Francisco Liton , Kung Michelle , Ness Emily , Battles Kevin , Landier Wendy , Salzman Donna E. , Weisdorf Daniel Jordan , Forman Stephen J. , Arora Mukta , Armenian Saro , Bhatia Smita
Published: March 2020

11572

Background: The association between TBI and breast SMN in BMT recipients is not clearly defined. We address this limitation to develop evidence for screening guidelines for those at risk. Methods: Study participants were drawn from BMTSS – a multi-site retrospective cohort of patients who had received BMT between 1974 and 2014 and survived ≥2y post-BMT. Participants completed the BMTSS survey that included sociodemographics and health conditions. Breast SMN was confirmed by pathology report review. Clinical characteristics, pre-BMT and BMT exposures were abstracted from medical records. Using multivariable Cox proportional hazards models, freedom from breast SMN was measured from birth and TBI was treated as a time-varying covariate in analyses stratified by type of BMT (allogeneic; autologous). Results: 1546 female participants (allogeneic 808; autologous 738) received BMT at a mean age of 43.1±17.6y and were followed for 9.4±7.7y; primary diagnoses: HL/NHL (28%), AML/MDS (27%), PCD (19%), other (28%). TBI was used in 671 patients (allogeneic 57%; autologous 30%). Patients with pre-BMT chest radiation (n = 45) were excluded from the analysis. A total of 38 cases of breast SMN were identified (allogeneic 19; autologous 19). Allogeneic BMT: exposure to TBI (HR = 3.4; 95%CI 1.1-10.9, p = 0.04) and age at BMT < 40y (HR = 4.0; 95%CI 1.3-12.8, p = 0.02) were associated with increased risk of breast SMN. Risk of breast SMN was higher and breast SMN developed earlier among those exposed to TBI before age 40y vs. those exposed after 40y (8.7% vs. 0% by attained age 50; 10.6% vs. 5.8% by attained age 60, p = 0.003). Autologous BMT: Age < 40y was associated with a 4.8-fold higher risk (95%CI 1.1-20.1, p = 0.03) of breast SMN. TBI was associated with a 2-fold higher risk (p = 0.2). The cumulative incidence of breast SMN among those exposed to TBI at age < 40y vs. age ≥40y was 5.1% vs. 2.4% by attained age 60 (p = 0.07). Conclusions: TBI is associated with breast SMN among allogeneic BMT recipients. The risk is especially high and occurs at a younger age, among those exposed at age < 40y. These findings provide evidence for initiating screening at a young age after exposure to TBI.
Comparison of the effectiveness of oral morphine versus oral tramadol on early pain control in opioid-naive patients with moderate cancer pain.
Authors: Shilpakar Ramila , Paudel Bishnu D. , Shah Aarati , Dulal Soniya
Published: March 2020

11581

Background: Adequate pain control, an essential part of cancer care remains a challenge in resource limited countries like Nepal. Early use of morphine for Moderate Cancer Pain (MCP) and not sequential World Health Organization (WHO) analgesic ladder seems reasonable in the setting of limited access to health care. The purpose of this study was to compare efficacy of oral Morphine (MOR) with oral Tramadol (TRM) in control of pain as well as physical wellbeing in patients (pts) with MCP using Edmonton Symptom Assessment Scale (ESAS). Methods: An IRB approved randomized phase II trial was performed in opioid-naive pts with MCP as defined by pain score in Numerical rating score (NRS)of 4-6.Patients were randomized to receive MOR syrup 5 mg 4 hourly or TRM 50 mg four times a day. Titration of dose was done in both groups for 3 days as per standard recommendation for MOR or till maximum recommended daily dose for TRM. MOR was changed to prolonged release form at Day 4.The primary endpoint was number of early responders, defined as pts with at least 20% reduction in pain intensity on NRS on Day 3. Secondary outcome was number of patients with highly meaningful pain reduction, defined as decrease in pain intensity on NRS by ≥ 5 and improvement in physical well-being with ESAS at Day 7. Results: 68 pts consented and were randomized, 34 in each arm. The primary endpoint occurred in 94.1% pts in MOR and 55.9% in TRM (p <0.001). Number of patients with highly meaningful pain reduction was significantly higher in MOR than in TRM (76.5% vs. 32.35%; p<0.001). Improvement in general physical wellbeing as assessed by ESAS was better in morphine group. No difference in adverse effects was noted between the treatment arms. Conclusions: In this study Morphine was superior to Tramadol in the control of pain with statistically significant difference in the primary and secondary endpoints. So, early use of morphine skipping the WHO sequential analgesic ladder for moderate cancer pain seems a higher value option in resource scarce country with limited access to healthcare.
Effect of patient education on palliative care knowledge and acceptability of outpatient palliative care service among gynecologic oncology patients.
Authors: Graul Ashley , Haggerty Ashley Ford , Stickley Carolyn , Kumar Pallavi , Morales Knashawn , Bogner Hillary , Burger Robert , Mark Morgan , Ko Emily
Published: March 2020

11583

Background: This was a randomized control trial to estimate the effect of an interventional video on improving palliative care knowledge and acceptability of outpatient services in gynecologic oncology patients. Methods: Women receiving active treatment for gynecologic malignancy (persistent or progressive disease despite primary treatment) were recruited at an academic tertiary care center from 2/2018 to 1/2019 and randomized to: palliative care educational video or non-directive cancer center informational video (control). The primary outcome was desire for referral to palliative care. Function and knowledge were assessed using the Functional Assessment of Cancer Therapy (FACT-G) and the Palliative Care Knowledge Scales. Data analyses were performed using t-tests, Wilcoxon rank sum or Fisher’s exact tests with significance level of α=0.05. Results: 111 women were enrolled. Demographic characteristics were equally distributed between groups (mean age 63.4 vs 65.4 years; 78% vs 82% Caucasian, 58% vs 68% stage III, 71% vs 64% ovarian cancer, 65% vs 72% platinum-sensitive). There was no statistical difference in knowledge scores or in desire for referral to palliative care (29% vs 27%; p=0.79). Secondary analysis showed a statistically significant increase in utilization of palliative care services compared to historic institutional data (8.8% to 29.7%; p=<0.001). Further, those that desired referral had significantly worse FACT-G scores at time of referral choice (table). Conclusions: Use of a palliative care educational video did not increase knowledge or acceptability of palliative care services within this RCT. However, the rate of patients seeking palliative care referral tripled compared to historic rates. Further studies should investigate whether discussion regarding palliative care services alone may increase desire for referral, and if use of Fact-G scores may identify patients in greatest need of services. [Table: see text]
Sex differences in adverse event reporting in SWOG chemotherapy, biologic/immunotherapy, and targeted agent cancer clinical trials.
Authors: Unger Joseph M. , Vaidya Riha , Albain Kathy S. , LeBlanc Michael Leo , Minasian Lori M. , Gotay Carolyn , Henry Norah Lynn , Fisch Michael Jordan , Ramsey Scott David , Blanke Charles David , Lyman Gary H. , Hershman Dawn L.
Published: March 2020

11588

Background: Women have more adverse events (AEs) from chemotherapy than men, but few studies have explored sex differences in biologic/immunotherapies (BIs) or targeted therapies. We examined subjective (symptomatic) and objective AEs by sex across different treatments. Methods: We analyzed drug-related severe (grade 3) or worse AEs by sex in SWOG phase II and III clinical trials conducted between 1980-2018, excluding sex-specific cancers. AE codes and grade were categorized using the Common Terminology Criteria for Adverse Events (CTCAE). Subjective or symptomatic toxicities were defined as those aligned with the NCI’s new Patient-Reported Outcome (PRO) CTCAE; lab-based or physician-determined AEs were designated as objective. Multivariable logistic regression was used, adjusting for age, race, and disease prognosis. Thirteen symptomatic and 19 objective AE categories were examined. Results: In total, 36,397 patients (women, 13,907 [38.2%]; men, 22,490 [61.8%]) experiencing 522,835 AEs on 297 trials with 385 treatment arms were analyzed. Overall, 29.1% (n = 10.860) had severe or worse toxicity. Women experienced an increased risk of severe symptomatic AEs for BIs (OR = 1.53, 95% CI: 1.32-1.78, p < .0001), chemotherapy (OR = 1.31, 95% CI: 1.24-1.39, p < .0001), and targeted therapies (OR = 1.23, 95% CI: 1.06-1.43, p = .008). Women also had an increased risk of severe objective AEs for BIs (OR = 1.53, 95% CI: 1.32-1.78, p < .0001), chemotherapy (OR = 1.35, 95% CI: 1.28-1.43, p < .0001), but not targeted therapies (OR = 1.08, 95% CI: 0.94-1.25, p = .28). Across all treatments, sex differences were greater for hematologic (OR = 1.29, 95% CI: 1.24-1.35, p < .0001) v. non-hematologic (OR = 1.13, 95% CI: 1.08-1.18, p < .0001) objective AEs. Conclusions: The greater severity of both symptomatic and objective – especially hematologic – AEs in women across multiple treatment paradigms indicates broad-based sex-differences exist. This could be due to AE reporting, pharmacogenomics of drug metabolism and disposition, total dose received, and/or adherence to therapy. Particularly large sex differences were observed for patients receiving BIs, suggesting studying AEs from these agents is a priority.
The effect of structured exercise during chemotherapy on chemotherapy-induced peripheral neuropathy (CIPN): A role for interoceptive brain circuitry.
Authors: Kleckner Ian , Gewandter Jennifer S. , Heckler Charles E. , Staples Susan , Colasurdo Ann , Lin Po-Ju , Shayne Michelle , Huston Alissa , Magnuson Allison , Tejani Mohamedtaki Abdulaziz , Dunne Richard Francis , Fung Chunkit , Lipe Brea , Passero Frank Charles , Mohile Nimish , Morrow Gary R. , Janelsins Michelle Christine , Mustian Karen Michelle
Published: March 2020

11590

Background: Over half of patients receiving “neurotoxic” taxane, platinum, or bortezomib chemotherapy experience CIPN—a dose-limiting toxicity involving numbness and pain in the extremities. There are no FDA-approved drugs for CIPN, but exercise may help. This randomized pilot study explored whether structured exercise during chemotherapy ameliorates CIPN symptoms and whether improvements involve changes in the brain’s sensory processing (interoceptive) circuitry. Methods: Nineteen patients scheduled to receive taxane, platinum, or bortezomib were randomized to exercise (home-based, low-moderate intensity, walking and resistance training; EXCAP) or nutrition education (control) for 12 weeks starting at their first infusion. At 0, 6, and 12 weeks, we assessed CIPN symptoms using the CIPN-20 questionnaire (sensory scale, ranges 9-36, higher is worse) and a finger tactile sensitivity task. We assessed resting functional connectivity between the insula and thalamus via fMRI at 0 and 12 weeks. We used linear regression to model each outcome, tested for an effect of exercise, and controlled for baseline value and age because controls were older. Given the pilot nature of this study we present effect sizes, not p-values. Results: The 19 patients were 65±11 years old, 52% women, with cancer: 42% breast, 32% gastrointestinal, 16% myeloma, and 10% genitourinary. Exercise mitigated CIPN symptoms per the CIPN-20 sensory scale. At 6 weeks, exercisers increased from 11.0 to 12.5 whereas controls increased from 11.0 to 15.5 (+1.5 vs. +4.5; ES = 0.81). At 12 weeks, exercisers increased from 11.0 to 14.8 whereas controls increased from 11.0 to 16.2 (+3.8 vs. +5.2, ES = 0.46). The finger-touching test corroborated results at 6 and 12 weeks (ES = 1.03 and 0.07). Exercisers showed better (reduced) insula-thalamus connectivity vs. controls (ES = 0.41). Reductions in connectivity were correlated with smaller increases in CIPN symptoms (r = 0.74). Conclusions: Exercise during neurotoxic chemotherapy mitigated CIPN symptoms, perhaps via improvements in interoceptive brain circuitry. Future work should test for replication with a larger sample. Clinical trial information: NCT03021174.
Physician concordance with update to ASCO guidelines for antiemetic use with carboplatin AUC ≥ 4.
Authors: Navari Rudolph M. , Ruddy Kathryn Jean , LeBlanc Thomas William , Clark-Snow Rebecca Anne , Wickham Rita S. , Binder Gary , Coberly Tammy Bratton , Potluri Ravi C. , Schmerold Luke M. , Roeland Eric
Published: March 2020

11595

Background: In 2017, NCCN (2/2017) and ASCO (8/2017) each amended antiemetic guidelines to classify carboplatin AUC ≥4 as highly emetogenic chemotherapy (HEC), recommending upfront triple prophylaxis with an NK1 receptor antagonist (RA) + 5HT3 RA + dexamethasone. Physician concordance with the new recommendations, and the consequences for avoidable post-chemotherapy acute care, merit study. Methods: In a large electronic health record database (IBM Explorys), we identified carboplatin courses of therapy (≥14-day cycles as a proxy for AUC ≥4) and courses with ≥7-day cycles of other HEC and non-HEC therapy from 4Q 2012 through August 2018. Guideline concordance, defined as triple prophylaxis at HEC initiation, was evaluated. We also assessed 30-day post-chemotherapy acute care (inpatient or emergency department) associated with nausea or vomiting (NV) or eight other toxicities deemed avoidable in the US Centers for Medicare & Medicaid’s new oncology outcome measure OP-35. Results: 11,554 carboplatin courses were identified. Before the guideline change, rates of upfront triple prophylaxis grew from 14% in 2013 to 16% in mid-2017. Rates then rose to 26% by 1Q 2018 before dropping to 21% by 3Q 2018; quarterly rates averaged 20% (range 15%-26%) following the guideline change. In 31% of carboplatin courses we noted 30-day acute care use, of which 75% involved ≥1 of the ten OP-35 toxicities. NV (with or without acute care use) was reported in 24% of courses, and 27% of total OP-35 acute care events involved NV. Rates for NV, and for OP-35-related and NV-related acute care after carboplatin, were similar to rates after other HEC chemotherapy, and higher than rates after other non-HEC IV chemotherapy or oral HEC/MEC agents. Conclusions: Use of upfront triple antiemetic prophylaxis has increased only marginally for carboplatin AUC ≥ 4 since its 2017 re-classification as HEC in national guidelines, perhaps due to low awareness of the change. Patients receiving carboplatin had similar rates of NV and related 30-day acute care events as seen for other HEC, confirming that the new HEC definition fits clinical experience. More triple prophylaxis use is needed to reduce NV and NV-related avoidable acute care seen with carboplatin AUC ≥ 4.
Effect of whey protein isolate supplementation on body composition, muscle strength, and treatment tolerance in malnourished advanced cancer patients undergoing chemotherapy.
Authors: Pedrazzoli Paolo , Cereda Emanuele , Cappello Silvia , Arcaini Luca , Borioli Valeria , Ferraris Elisa , Chiellino Silvia , Stella Giulia , Benazzo Marco , Ferrari Alessandra , Klersy Catherine , Caccialanza Riccardo
Published: March 2020

11598

Background: Malnutrition is frequent in cancer pts, particularly in advanced disease, which requires appropriate multidisciplinary interventions. We evaluated the benefit of whey protein isolate (WPI) supplementation in addition to nutritional counseling in malnourished cancer pts undergoing chemotherapy (CT). Methods: In a single-center, randomized, pragmatic, parallel-group controlled trial (ClinicalTrials.gov: NCT02065726), 166 malnourished advanced cancer pts undergoing CT were randomly assigned to receive nutritional counseling with (N=82) or without (N=84) WPI supplementation (20 grams/daily) for 3 months. Primary endpoint was the change in phase angle (PhA). Secondary endpoints included changes in standardized PhA (SPA), fat-free mass index (FFMI), body weight, muscle strength, quality of life and CT toxicity. Results: In pts with the primary endpoint assessed (modified intention-to-treat population), counseling plus WPI (N=66) resulted in improved PhA compared to nutritional counseling alone (N=69): mean difference, 0.48° [95%CI, 0.05 to 0.90] (P=0.027). Imputation of missing outcomes yielded consistent findings. WPI supplementation resulted also in improved SPA (P=0.021), FFMI (P=0.041), body weight (P=0.023), muscle strength (P<0.001) and in reduced risk of CT toxicity, particularly of severe (grade ≥3) events (Table). Conclusions: In malnourished advanced cancer patients undergoing CT and receiving nutritional counseling, 3-month supplementation with WPI resulted in improved body composition, muscle strength, body weight and reduced CT toxicity. Further trials in newly diagnosed specific cancer types are warranted. Clinical trial information: NCT02065726. [Table: see text]
Interim analyses of the efficacy of a collaborative care intervention for patients diagnosed with comorbid cancer and depression.
Authors: Steel Jennifer Lynne , Miceli Jessica , Hecht Carol Lynn , Tsung Allan , Marsh Wallis , Antoni Michael , Vodovotz Yoram , Peddada Shaymal , Spring Michael , Jackson Heather , Vanegas Yanet , Olejniczak Donna , Chen Qi , Geller David A.
Published: March 2020

11599

Background: There is an urgent need for evidence-based and scalable interventions to reduce depression, pain, and fatigue and improve quality of life in patients diagnosed with cancer. The aims of this study were to share the interim analyses of testing the efficacy of a stepped collaborative care intervention for patients diagnosed with cancers affecting the hepatobiliary and pancreatic system. Methods: Patients were screened for clinical levels of depression, pain, or fatigue and were enrolled in the study if they screened positive for depression, pain, and/or fatigue. After completing a baseline battery of instruments, patients were randomized to the stepped collaborative care intervention or the screening and referral arm. Post-treatment data was collected at 6 months and 12 months to assess efficacy and maintenance of change in depressive symptoms. Results: A total of 100 patients have completed the post-treatment assessment. Interim data analyses revealed that the mean age of patients was 64.0 years (SD = 10.3) and the majority of patient were male (51%), Caucasian (89%), diagnosed with liver cancer (47%) and stage III and IV (60%). Patients randomized to the stepped collaborative care intervention reported significant reductions in depressive symptoms (F(1,92) = 6.22, p = 0.014) and improvements in quality of life (F(1,92) = 7.36, p = 0.008) with moderate effect sizes (Cohen’s d = 0.547 and 0.652, respectively) at 6-months. The mean change in depressive symptoms from randomization to 6-month post- treatment was -4.3 (SD = 9.7) for the patients randomized to the collaborative care intervention and +0.71 (SD = 9.4) for the patients randomized to the screening and referral arm of the study. The mean change in quality of life from randomization to 6-month post-treatment was +4.5 (SD = 16.2) for the patients randomized to the collaborative care intervention and -4.4 (SD = 15.2) for the patients randomized to the screening and referral arm of the study. Conclusions: This promising evidence-based, scalable intervention to treat comorbid cancer and depression was shown to be effective in reducing depressive symptoms and improving quality of life in patients with cancer. Clinical trial information: NCT02939755.
Progress and trends in the utilization and adoption of palliative care in patients with terminal gynecologic cancer in the United States: A study of 4,264 women.
Authors: Milki Anthony , Mann Amandeep Kaur , Kapp Daniel Stuart , Chan John K.
Published: March 2020

11606

Background: To determine the factors associated with the utilization of palliative care (PC) in patients with metastatic gynecologic cancer who died while hospitalized. Methods: Data were extracted from the National Inpatient Sample (NIS) database for patients with cervical, uterine, and ovarian cancers from 2005 to 2011. Chi-squared and logistic regression models were employed for statistical analyses. Results: Of 4264 women with gynecologic cancer, 983 (23.0%) utilized PC (median age: 66 years). 2633 (61.8%), 1034 (24.3%), and 597 (14.0%) patients had ovarian, uterine, and cervical cancer, respectively. The majority were white (57.9%), and the remainder were black (12.6%), Hispanic (7.8%), and Asian (3.1%). 24.9, 23.9, 23.6, and 25.2% were low, low-middle, middle-high, and high with respect to median income. Medicare, Medicaid, and private insurance was found in 46.7, 10.8, and 37.6% of patients. 36.9, 21.0, 18.0, and 24.1% of patients were treated in hospitals in the South, West, Midwest, and Northeast. 11.3, 23.9, and 64.2% of patients were treated in small, medium, and large hospitals, designated as teaching (53.1%) and nonteaching (46.3%) institutions. The utilization of PC increased from 5.2% in 2005 to 30.4% in 2011. Older age (OR: 1.34; 95% CI: 1.10-1.64; P = 0.01), high SES (OR: 1.37; 95% CI: 1.09-1.72; P = 0.01), privately insured (OR: 1.81; 95% CI: 1.46-2.24; P < 0.001), treatment at Western (OR: 1.94; 95% CI: 1.56-2.41; P < 0.001) and Midwestern hospitals (OR: 1.43; 95% CI: 1.15-1.77; P = 0.001), and depression (OR: 1.34; 95% CI: 1.00-1.80; P = 0.05) were associated with higher PC use. However, race, cancer type, hospital teaching status, and hospital location were not associated with PC use. Conclusions: The use of inpatient palliative care has increased significantly over the study period. The lower utilization of palliative care for terminal illness associated with younger, lower socioeconomic status, Southern and smaller volume hospitals warrants further attention.
The individualized Goals of Care Discussion Guide: A simple tool to empower patients with metastatic breast cancer.
Authors: Peppercorn Jeffrey M. , Lei Yvonne Y. , Horick Nora , Quain Katharine M. , Dizon Don S. , Jimenez Rachel , Shin Jennifer Adrienne , Sepucha Karen , Perez Giselle Katiria
Published: March 2020

11622

Background: Individualized treatment planning is a critical part of quality cancer care, but how best to achieve this for patients with metastatic breast cancer (MBC) is unclear. We evaluated the feasibility, acceptability and impact of using a simple and scalable “Individualized Goals of Care Discussion Guide” (IGCDG) to facilitate patient-provider communication at the time of treatment decisions. Methods: We developed the IGCDG based on structured interviews with MBC patients and input from experts in cancer care, decision sciences, psychology and palliative care. We then conducted a single arm feasibility trial among patients with newly diagnosed or progressive MBC. Prior to clinic, patients received the IGCDG, an 8-page MBC informational brochure and 1-page questionnaire regarding treatment preferences, personal goals and priorities for care planning. The completed questionnaire was provided to the oncology team at the patient’s visit. Pre and post assessment included the Distress Thermometer (DT), Patient Satisfaction with Cancer Care Scale and the Control Preferences Scale. Feasibility was defined as: 1) accrual of > 50%, 2) attrition rate < 32%, and 3) < 50% of patients experiencing increased distress following the intervention. Results: Among 60 eligible patients, 42 participated (70% accrual), 40 completed all surveys (2% attrition), and only 7 (18%) reported increased distress. Mean age was 57 (range 31 – 79), 85% were white, 7% black, 5% Hispanic, 66% were college graduates, and 40% reported high baseline distress (DT > 4). Patient priorities for discussion included cancer directed therapy (70%), symptom management (70%), and prognosis/planning ahead (60%). At 2-month follow-up, 53% reported decreased distress compared to baseline. Satisfaction with cancer care was high at baseline and follow-up. Most patients preferred shared decision making (77%), and 79% reported decision roles concordant with preferences. Overall, 72% of participants found the IGCDG helpful, 93% found the questionnaire easy to complete, and 44% felt it improved communication with their doctor (49% unsure). Conclusions: Administration of the Individualized Goals of Care Discussion Guide is feasible and provides patients with MBC an opportunity to define their goals of care and priorities for discussion in clinic. Clinical trial information: NCT03375827.
Effectiveness of psychological distress reduction with cognitive behavioral therapy for oncological patients: A one-year follow-up study.
Authors: Rossi Alessandro , Marconi Maria , Mannarini Stefania , Minelli India , Anderboni Monica , Rossini Chiara , Di Lucca Giuseppe , Verusio Claudio
Published: March 2020

11624

Background: Distress has a negative impact on medical treatment (Di Matteo, Lepper & Croghan, 2006) and it is considered one of the most important indexes of psychological suffering in oncological patients (NCCN, 2015). Thus, the purpose of this study was to determine the long term effectiveness of brief Cognitive Behavioral Therapy for patients with cancer (CBT-C) compared with a control group (CG) of oncological patients without any psychotherapy intervention - at one year after a chemotherapy treatment. Methods: Participants ( n = 80; mean age = 63.3, SD = 13.4; 54 female) enrolled at the Oncology Day Hospital at the “Presidio Ospedaliero” of Saronno, ASST Valle Olona, Italy who undertook (CBT-C: n = 40) or non-undertook (CG: n = 40) a psychotherapy intervention. Individual psychotherapy sessions strictly followed the IPOS guidelines (Watson & Kissane, 2017). Participants were tested with the Psychological distress Inventory (PDI) at the baseline (T1; Cronbach α = .88) at the end of the chemotherapy treatment (T2; Cronbach α = .87), at the end of the psychotherapy intervention (T3; Cronbach α = .88), 6-month follow-up (T4; Cronbach α = .85), and 1-year follow-up (T5; Cronbach α = .84). Results: Multilevel growth curve modeling – controlling for age, number of sessions, type and localization of tumor – showed a sharper reduction of distress for CBT-C participants that continue after posttreatment until 1-year follow-up ( p < .001); whereas for CG participants it reduced more gradually from pretreatment to 1-year follow-up ( p < .001). The results revealed a significant difference between the linear slopes for each treatment condition ( p < .001). The overall Hedges’ g comparing the two groups for distress reduction between pretreatment and 1-year follow-up was 2.14 (p < .001) in favor of CBT-C. Conclusions: Given that psychological distress occurs frequently among oncological patients this study is into an important area of study. Results suggest that CBT-C is statistically and clinically effective in treating psychological distress 1 year after the chemotherapy treatment. These findings revealed a kind of long-term effectiveness psychological intervention able both to reduce psychological suffering and improve a better quality of life in oncological settings.
Till death do us part: Existential loneliness (EL), psychosocial distress, and survival of advanced cancer patients (ACPs), and their spousal caregivers (SCs).
Authors: Hlubocky Fay J. , Sher Tamara , Cella David , Ratain Mark J. , Daugherty Christopher
Published: March 2020

11628

Background: Terminally-ill ACP often experience existential suffering as they near the end-of-life. However, the specific impact of EL on ACP and SC psychosocial wellness and survival has yet to be identified. Methods: A prospective ACP cohort enrolled in phase I trials was assessed at baseline (T1) and at one month (T2) utilizing psychosocial measures: state/trait anxiety (STAI-S/T), depression (CES-D), quality of life/QOL (FACIT-Pal), and global health (SF-36). Semi-structured interviews evaluated the ACP-SC EL experience: cognitive awareness (e.g. death, terminal prognosis); and, emotions (physical isolation; emptiness; abandonment). Results: To date, 160 participants (80 Phase I ACP and 80 SC) have been separately interviewed at T1 and T2. Total population demographics include: median age 62 (28-78y); 50% male; 100% married; 89% Ca; 68% > HS educ; 58% GI dx; ACP median survival 8.3 months (.51-18.9) 55% income < $65,000 yr. At T1, 77% of ACP acknowledged a cognitive awareness of death, 72% reported physical isolation; 54% felt emotional emptiness. For SC at T1, 65% recognized a cognitive awareness of death; 89% felt isolated; and 82% sensed emotional abandonment. Over time, rates of EL remained consistent for ACP-SC with the exception of increased self-reported isolation at 79% and 92% respectively at T2. At T2, ACP with death cognitions had higher STAI-S (32±10 v. 30±11, p = 0.03) and CES-D scores (13±12 v. 11±10, p = 0.02). SC with self-reported abandonment had higher STAI-S anxiety (39±17 v. 35±13, p = 0.03) at T2. Regression analyses revealed ACP with EL death cognitions had poorer FACIT-Pal QOL over time. Moreover, SC with self-reported physical isolation at T2 was negatively associated with SF-36 scores. ACP with EL had shorter overall survival compared to ACP without EL (4.1 v. 6.9 months, p = 0.02). ACP and SC qualitative inquiry re EL exposed unique themes: difficulty articulating EL experience; acceptance of death; finding meaning within crisis. Conclusions: EL is negatively associated with QOL for ACP participating in Phase I trials. Supportive couples-based, dyadic psychological interventions at the end-of-life to assist with coping are warranted.
Off-the-shelf virus specific T-cells for therapy of adenovirus disease in immunosuppressed patients.
Authors: Rafei Hind , Imahashi Nobuhiko , Basar Rafet , Banerjee Pinaki Prosad , Daher May , Ganesh Christina , Hosing Chitra , Kaur Indreshpal , Kebriaei Partow , Khouri Issa F. , Mehta Rohtesh , Nieto Yago , Olson Amanda Leigh , Qazilbash Muzaffar H. , Spencer Bryan P , Srour Samer , Shpall Elizabeth J. , Champlin Richard E. , Marin David , Rezvani Katayoun
Published: March 2020

7008

Background: Adenovirus infection can cause significant morbidity and mortality in immunosuppressed patients. Cidofovir is commonly used, but its nephrotoxicity is concerning and efficacy limited. Another approach is to restore the anti-adenovirus immunity. Indeed, virus specific T-cells have been shown to be safe and effective in stem cell transplant recipients. Methods: Immunosuppressed pts with either adenovirus viremia or adenovirus-related end organ damage were enrolled. Most closely HLA-matched adenovirus cytotoxic T lymphocytes (CTLs) were generated by expanding donor derived T-cells with a peptide library derived from the hexon protein of adenovirus serotype 3 in the presence of IL-2 20 IU/ml, IL7 10 ng/ml, IL4 10 ng/ml. After receiving 2x105 /kg T cells, pts were monitored for response and adverse events. Results: Eight pts received adenovirus CTLs with one infusion. The Table summarizes their characteristics and responses. Seven pts had complete resolution of their symptoms (CR) and adenovirus becoming undetectable (ND). Those pts are alive to date. The remaining patient initially responded but then lost the response when started on high dose prednisolone for treatment of GVHD to which she eventually succumbed. Best response was achieved after a median time of 13 days [10-36]. No cytokine release syndrome occurred and we did not observe any side effect attributable to the CTLs. Conclusions: The use of off-the-shelf adenovirus CTLs is a feasible, safe, and effective approach to treat severe adenovirus infections in immunosuppressed pts. Clinical trial information: NCT03425526. [Table: see text]
Treatment-free remission (TFR) following frontline (1L) nilotinib (NIL) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP): 192-week data from the ENESTfreedom study.
Authors: Giles Francis J. , Masszi Tamas , Gómez Casares María Teresa , Hellmann Andrzej , Stentoft Jesper , Conneally Eibhlin , García Gutierrez Valentin , Gattermann Norbert , Le Coutre Phillipp D. , Martino Bruno , Saussele Susanne , Radich Jerald P. , Ross David M. , Saglio Giuseppe , Sondhi Manu , Acharyya Suddhasatta , Aimone Paola , Hochhaus Andreas
Published: March 2020

7013

Background: In ENESTfreedom (NCT01784068), which evaluated TFR following 1L NIL in CML-CP pts, 51.6% remained in TFR 48 wks after stopping treatment (primary endpoint) and durability of TFR was demonstrated at 144 wks. Data from longer follow-up (192 wks) evaluating maintenance of TFR are reported. Methods: Pts with MR4.5 ( BCR-ABL1IS ≤0.0032%) and ≥2y of 1L NIL entered a 1y consolidation; pts with sustained deep molecular response (MR) were eligible for TFR. NIL was resumed after loss of major MR (MMR; BCR-ABL1IS ≤0.1%). At the latest data cut-off (Sep 17 2018), all pts had completed ≥192 wks of TFR, resumed NIL, or discontinued the study. Results: By the data cut-off, of 190 pts entering TFR, 87 were ongoing, 91 had resumed NIL, and 12 had permanently discontinued. The TFR rate at 192 wks was 44.2% (84/190, 95% CI: 37.0–51.6%). Of 89 pts with successful TFR at 144 wks, 5 were not assessable for TFR at 192 wks as 2 had discontinued by 192 wks due to pt/physician decision, and 3 with MR4.5 previously did not have 192 wk PCR data. Of 91 pts who resumed NIL, 90 (98.9%) regained MMR and 84 (92.3%) regained MR4.5. 75/90 and 73/84 pts, respectively, had stable MMR and MR4.5 at 48 wks later. There were no cases of disease progression or new deaths. 10 deaths were reported in the 144-wk analysis, none due to CML. The 192-wk treatment-free survival rate was 48.7% (95% CI 41.4–55.6%). Of 89 pts remaining in TFR for > 144 wks (including 87 pts for > 192 wks), all-grade AE rates during consolidation and each subsequent 48 wk period of TFR were 84.3%, 77.5%, 70.8%, 48.3%, and 52.8%, respectively. All-grade musculoskeletal pain AE rates were 15.7%, 40.4%, 9.0%, 3.4% and 3.4%, respectively; cardiovascular event rates were low across these periods. Among pts who resumed NIL, most common AEs were nasopharyngitis (18.7%) and pruritus, fatigue, and increased lipase (14.3% each); the majority of AEs were grade 1/2. Conclusions: Results continue to support the long-term durability and safety of TFR at 192 wks after stopping 1L NIL; overall AE rates declined during the TFR phase and musculoskeletal pain AEs were transient. Pts should continue to be regularly monitored during TFR. Clinical trial information: NCT01784068.
Allogeneic hematopoietic stem cell transplantation contributes to eradication of minimal residual disease in adult Philadelphia chromosome-positive acute lymphoblastic leukemia patients treated with dasatinib.
Authors: Chang Jeremy , Akhtari Mojtaba
Published: March 2020

7024

Background: Philadelphia Chromosome-Positive (Ph+) disease is associated with a poor prognosis in acute lymphoblastic leukemia (ALL). Recent studies have shown that the eradication of minimal residual disease (MRD) in this population leads to improved survival outcomes. While hematopoietic stem cell transplantation (HSCT) has demonstrated clinical benefits in Ph+ ALL patients treated with the tyrosine kinase inhibitor (TKI) imatinib, its role is less clear with the use of more potent, newer-generation TKIs such as dasatinib. Methods: This was a retrospective study analyzing the impact of allogeneic HSCT on MRD status in Ph+ ALL patients treated with dasatinib. Patients were divided into 2 groups: those treated with chemotherapy plus dasatinib followed by allogeneic HSCT and those who received chemotherapy plus dasatinib alone. All patients underwent bone marrow biopsy with MRD analysis following induction therapy and subsequent re-evaluation of MRD status at day 100 post-transplant in the HSCT group and after further cycles of chemotherapy plus dasatinib in the non-transplant group. MRD-negative disease was defined as the absence of a BCR-ABL1 transcript by real-time quantitative polymerase chain reaction (qRT-PCR) with a sensitivity of 0.01%. Results: A total of 51 adult Ph+ ALL patients with MRD-positive disease following induction therapy were included. Twenty-seven patients (53%) were male and the median age at time of diagnosis was 42 years (range 23-68). There were 29 patients in the transplant group and 22 patients in the non-transplant group. When analyzing rates of MRD eradication, 18 (62%) patients in the transplant group were found to have MRD-negative disease at day 100 post-transplant compared to 7 (32%) patients in the non-transplant group who only received further cycles of chemotherapy plus dasatinib (risk ratio 0.56, 95% confidence interval 0.32-0.96, p = 0.048). Conclusions: In the era of newer-generation TKIs, allogeneic HSCT continues to have notable benefits in Ph+ ALL such as a significantly higher rate of MRD eradication as demonstrated in this study.
Mechanism of biologic therapy for pre B-cell acute lymphoblastic leukemia with CRLF2 overexpression.
Authors: Watson WayAnne , Stoian Cornelia , Coats Jacqueline S. , AlKashgari Hossam , Vidales Veriah , Baez Ineavely , Personius Juliette , Choi Hannah , Becerra Benjamin , Chavan Rishikesh , Kamal Muhammad Omair , Farzin Gohar Shadi , Payne Kimberly J
Published: March 2020

7035

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, of which pre B-cell ALL with CRLF2 overexpression is a high risk subtype. CRLF2 B-ALL is associated with poor outcome, increased rate of relapse, and health disparities in Hispanic children. Together with IL-7 receptor alpha (IL-7Rα), CRLF2 makes up a receptor complex that is activated by the cytokine, thymic stromal lymphopoetin (TSLP). Activation of the receptor complex leads to JAK2/STAT5 and PI3/AKT/mTOR signals that promote leukemia cell survival and proliferation. To study the role of TSLP in CRLF2 B-ALL, we developed a patient-derived xenograft (PDX) model of CRLF2 B-ALL that allows us to alter circulating levels of human TSLP (hTSLP). We generated PDX from CRLF2 B-ALL cells harvested from patient samples and compared leukemia burden in mice with varying levels of hTSLP. In PDX models with hTSLP levels at or below physiological levels in pediatric cancer patients, CRLF2 B-ALL cells grew robustly. However, in PDX with elevated levels of hTSLP, leukemia cells were essentially eliminated. Our objective is to elaborate on the mechanism of high dose hTSLP’s antileukemic effect. Methods: We performed TSLP dose response studies and used flow cytometry to evaluate the effect of TSLP on SOCS protein expression, CRLF2 signaling shutdown, and loss of TSLP receptor components. Results: CRLF2 B-ALL cells cultured with hTSLP showed a dose-dependent loss in the ability to induce STAT5 and S6 phosphorylation following hTSLP stimulation. This loss was correlated with the loss of IL-7Rα, and maintained for 24-48 hours following a pulse of high-dose, but not low-dose, hTSLP. The loss of signaling and surface IL-7Rα could be prolonged if high-dose hTSLP levels were maintained. Flow cytometry analysis showed that high-dose hTSLP upregulated SOCS1 and SOCS3 proteins in CRLF2 B-ALL cells. Whole genome microarray showed that SOCS1, SOCS2, SOCS3 and CISH mRNA were upregulated in primary CRLF2 B-ALL cells cultured with high dose hTSLP. Conclusions: These data support the hypothesis that TSLP exerts its anti-leukemia effects through shutdown of CRLF2-mediated signals and that these effects are at least partially mediated by the loss of the IL-7Rα component, and potentially through SOCS family proteins. These studies elucidate the mechanism of the human TSLP cytokine as a potential biologic therapy to treat CRLF2 B-ALL. Supported in part by 1R01CA209829 (KJP), 1R43CA224723 (KJP), ASH HONORS Award 2018-2019 (WBW), and Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship 2018-2019 (WBW).