bluuebunny/crossref_metadata_2025 huggingface dataset:
SAR-096: A phase II trial of ribociclib in combination with everolimus in advanced dedifferentiated liposarcoma (DDL), and leiomyosarcoma (LMS).
Authors: Movva Sujana , von Mehren Margaret , Handorf Elizabeth A. , Morgan Jeffrey A. , Nathenson Michael , Thornton Katherine Anne , Tetzlaff Eric Daniel , Barker Emma , Thibodeau Linda , Harley Allisa Cherae , King April , Veggeberg Rosanna , Leshner Juliet A. , Rink Lori , George Suzanne
Published: May 2020

11544

Background: Inhibition of CDK4 is being studied in a variety of sarcomas, especially dedifferentiated liposarcoma (DDL) where prolonged progression free survival has been noted. Exposure to CDK4 inhibitors in Rb+ leiomyosarcoma (LMS) cell lines leads to decreased cell proliferation, and increased senescence, and G0/G1-phase arrest. When combined, ribociclib a CDK4 inhibitor and everolimus, an mTOR inhibitor show synergistic growth inhibition in multiple tumor models. Methods: Patients (pts) were enrolled to one of two cohorts: DDL or Rb+ LMS. LMS pts were required to have 1 prior line of therapy; DDL pts required no prior therapy. There were no limits to prior therapies in either group. Progression on prior therapy and measurable disease by RECIST 1.1 was also required. Ribociclib was given at 300 mg daily for 21/28 days and everolimus was given continuously at 2.5 mg daily in 28 day cycles. The primary endpoint was progression free rate at 16 weeks. A Simon two-stage design was utilized and if at least 8 out of 24 pts were progression free at 16 weeks, the treatment was declared promising for the cohort. Here in we present data on the LMS cohort. Results: Twenty-four LMS pts, 83% (n = 20) female, 58% (n = 14) uterine primary were treated. Median prior lines of therapy was 3.5 (range 1-9). Of 22 pts with complete data, 6 (27.2%) met the primary endpoint of non-progression at 16 weeks. Median PFS was 19.6 weeks (range 2.8-84), with progression as best response occurring in 13 pts. There were no objective responses. Five pts who had progressive disease on multiple lines of therapy experienced prolonged progression free survival (23-84 weeks). Grade 3-4, toxicities included neutropenia (29%), thrombocytopenia (12.5%) and leucopenia (12.5%) being most common. Tissue samples pre and on therapy as well as blood were collected in 21 and 18 pts respectively to evaluate pharmacodynamic changes. Conclusions: Final data on the primary endpoint for the LMS cohort is pending; it is notable that several heavily pre-treated LMS pts experienced prolonged progression free survival for > 9 months. Updated results and biology correlatives will be presented. Clinical trial information: NCT03114527 .
A phase I trial of pomalidomide in combination with liposomal doxorubicin in patients with Kaposi sarcoma with or without other KSHV-associated diseases.
Authors: Ramaswami Ramya , Lurain Kathryn Anne , Widell Anaida , Goncalves Priscila Hermont , Ekwede Irene , Figg William Douglas , Peer Cody J. , Mangusan Ralph , George Jomy , Steinberg Seth M. , Khetani Vikram , Whitby Denise , Uldrick Thomas S. , Yarchoan Robert
Published: May 2020

11552

Background: Kaposi sarcoma herpesvirus (KSHV, also known as human herpesvirus 8 [HHV-8]), is the causative agent of Kaposi sarcoma (KS), a multicentric angioproliferative tumor, a form of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). KS can be difficult to treat when it occurs with KSHV-MCD or KICS; resulting in high mortality rates. Liposomal doxorubicin (LD) is an FDA-approved treatment for KS. Pomalidomide, an oral immunomodulatory drug, is safe and has demonstrated activity in KS, but the activity of the combination (pomalidomide+LD) in KS alone or with KSHV-associated diseases is unknown. Methods: The primary objective was to evaluate safety and tolerability of pomalidomide+LD in two groups of patients with KS requiring systemic therapy: Group I (GI)- KS alone; Group II (GII)- KS with concurrent KSHV-MCD or KICS. Patients received LD at 20 mg/m2 intravenously on day 1 of a 28-day cycle combined with pomalidomide once daily on days 1 to 21 at escalating dose levels (DL) (I - 2mg, II - 3mg, or III- 4mg) in a 3+3 design until plateau of response or other pre-specified criteria. Patients received 81mg of aspirin daily as thromboprophylaxis. KS responses were evaluated using the modified AIDS Clinical Trial Group criteria. Results: Thirty-four cisgender men, all with T1-stage KS [21 patients (62%) in GI and 13 patients (38%) in GII] were treated; 32 (94%) were HIV-infected and 22 (65%) had prior chemotherapy for KS (15/21 GI and 7/13 GII). There were no dose-limiting toxicities (DLTs) at DLIII for GI, and additional patients were treated at DLIII. In GII, grade 3 rash and pharyngeal edema were DLTs observed at 3mg of pomalidomide. Overall a median of 6 cycles were administered; the most common grade 3/4 toxicity was neutropenia. Among evaluable patients receiving >2 cycles,17/21 patients in GI had a response (all partial) (81% [95% confidence interval (CI) 58-95%]) and 5/10 patients in GII had a response (4 partial and 1 complete) (50% [95% CI 19-81%]). Conclusions: Pomalidomide+LD was well-tolerated and active in heavily pretreated patients with KS alone. In patients with KS and other KSHV-associated diseases, activity was noted but less well-tolerated. Clinical trial information: NCT02659930 .
Phase II study of eribulin and pembrolizumab in patients (pts) with metastatic soft tissue sarcomas (STS): Report of LMS cohort.
Authors: Nathenson Michael , Choy Edwin , Carr Neena D , Hibbard Hayley D , Mazzola Emanuele , Catalano Paul J. , Thornton Katherine Anne , Morgan Jeffrey A. , Cote Gregory Michael , Merriam Priscilla , Wagner Andrew J. , Demetri George D. , George Suzanne
Published: May 2020

11559

Background: Responses to single agent PD-1/PD-L1 inhibitors in STS remain limited with occasional responses in undifferentiated pleomorphic sarcomas (UPS), liposarcomas (LPS), and other sarcomas, and rare responses in leiomyosarcoma (LMS). Since cytotoxics and/or targeted therapies such as CDK4/6 inhibitors may alter the tumor microenvironment (TME) and potentiate the effect of immunotherapy, combination approaches may be needed to potentiate STS immunotherapy. The mechanism by which eribulin controls LPS may involve TME modification, and therefore it is attractive to test in combination with pembrolizumab in STS subtypes. This report summarizes the results from the LMS cohort from this ongoing trial. Methods: Pts treated with at least one prior therapy received eribulin 1.4mg/m2 (day 1, 8) and pembrolizumab 200mg (day 1), every 21 days. Pts continued therapy until progressive disease, death, or unacceptable toxicity. Primary endpoint was progression-free survival (PFS) at 12 weeks, with 60% PFS at 12 weeks required to deem the combination promising. Tumor assessments (RECIST 1.1) were performed at screening and every 6 weeks thereafter. Secondary endpoints included overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Results: Nineteen pts with LMS were enrolled from May 2019 to Sept 2019. The median age was 62 (range 48-80). Eleven (58%) patients had uterine LMS. The median # of prior therapies was 4 (range 1-7). The median follow-up was 19.7 weeks. The PFS at 12 weeks was 42.1% (90% CI: 27.0%-65.5%), with median PFS of 11.1 weeks. Median OS was not reached during the follow-up period. There was 1 partial response, and 5 confirmed stable disease for ORR of 5.3% and CBR of 26.3%, after 12 weeks. The rate of grade 3 or higher toxicity was 68% overall, most commonly neutropenia, anemia, weight loss, diarrhea, elevations of lipase, and alkaline phosphatase. These side effects were reversible. The most common adverse events were fatigue, neutropenia, anorexia, AST increase, and nausea. Conclusions: Eribulin and pembrolizumab in LMS did not meet the predefined endpoint for efficacy. The LPS and “other STS subtype” cohorts of this trial are actively enrolling. Clinical trial information: NCT03899805 .
Cost-utility analysis of surveillance strategies for soft tissue sarcoma recurrence.
Authors: Chau Bonny , Zimmermann Marita , Wagner Michael , Cranmer Lee D.
Published: May 2020

11565

Background: Soft tissue sarcomas (STS) are uncommon malignancies with significant biological and clinical variation. After primary curative therapy, patients enter a program of surveillance for recurrence with periodic chest x-rays (CXR) or computed tomography (CT). We compared costs and health outcomes of CXR and CT at a range of frequencies and durations of follow-up. Methods: We used a Markov model to simulate a cohort of 10,000 STS patients through their surveillance experience for lung metastasis after completion of definitive treatment for stage II or III primary disease. Health states in the model were no evidence of disease, recurrence, and death. We assessed the method of chest imaging, duration of follow-up, and interval (every 3 months or 6 months) of surveillance in the first 3 years. Cost effectiveness was assessed for each screening modality and screening frequency. Recurrence probabilities, utilities, treatment costs, and other parameters were from previously published data. Outcomes were costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER). Results: The initial evaluation comparing screening every 3 months for 3 years, every 6 months for years 4 and 5, and annually from years 6 to 10 resulted in 632,264 QALYs and $1,038,351,481 costs for CT, compared to 631,834 QALYs and $746,019,937 for CXR, resulting in an ICER of $679,322/QALY. In comparing screening intervals, less frequent screening intervals of every 6 months compared to every 3 months for the first three years using CT resulted in an ICER of $690,527/QALY and for CXR, the ICER was $271,423/QALY. In comparing screening duration between 6 years and 10 years of follow-up, strategies with longer follow-up resulted in slightly higher QALYs in each of the comparison scenarios, at a much higher cost. Conclusions: In our evaluation, more frequent screening the first 3 years and longer duration of surveillance resulted in higher QALYs in both screening modalities. However, in the comparisons the ICERs exceed common willingness to pay thresholds of $150,000/QALY gained; CXR is the more cost-effective imaging modality. Limitation of this model includes the simplification of disease progression and heterogeneity in STS.
Multisite randomized trial of integrated palliative and oncology care for patients with acute myeloid leukemia (AML).
Authors: El-Jawahri Areej , LeBlanc Thomas William , Kavanaugh Alison , Webb Jason , Jackson Vicki A. , Campbell Toby Christopher , O'Connor Nina , Luger Selina M. , Gafford Ellin , Gustin Jillian , Bhatnagar Bhavana , Fathi Amir Tahmasb , Hobbs Gabriela , Foster Julia , Nicholson Showly , Davis Debra M. , Addis Hilena , Vaughn Dagny , Horick Nora K. , Temel Jennifer
Published: May 2020

12000

Background: Patients with AML receiving intensive chemotherapy experience substantial decline in their quality of life (QOL) and mood during their hospitalization for induction chemotherapy and often receive aggressive care at the end of life (EOL). We sought to examine the effect of integrated palliative and oncology care on QOL, mood, post-traumatic stress (PTSD) symptoms, and EOL outcomes in patients with AML. Methods: We conducted a multi-site randomized trial of integrated palliative and oncology care (n = 86) versus usual oncology care (n = 74) for patients with AML undergoing intensive chemotherapy. Patients assigned to the intervention were seen by palliative care clinicians at least twice per week during their hospitalization for induction chemotherapy and all subsequent hospitalizations. Patients completed the Functional Assessment of Cancer Therapy-Leukemia, the Hospital Anxiety and Depression Scale, and the PTSD Checklist to assess their QOL, mood, and PTSD symptoms at baseline, weeks 2, 4, 12, and 24. The primary endpoint was QOL at week-2. We used analysis of covariance and mixed linear effect models, controlling for baseline scores, to assess the effect of the intervention on patient-reported outcomes. Results: Between 1/2017 and 7/2019, we enrolled 160/235 (68.1%) of eligible patients. Compared to those receiving usual care, intervention patients reported better QOL (107.59 vs. 116.45, P = 0.039) and lower depression (7.20 vs. 5.68, P = 0.021), anxiety (5.94 vs. 4.53, P = 0.018), and PTSD symptoms (31.69 vs. 27.79, P = 0.009) at week 2. Intervention effects were sustained up to week 24 for QOL (B = 2.35, P = 0.048), depression (B = -0.42, P = 0.039), anxiety (B = -0.38, P = 0.042), and PTSD symptoms (B = -1.43, P = 0.002). Among deceased participants, those receiving the intervention were more likely to report discussing their EOL care preferences with their clinicians (75.0% vs. 40.0%, P = 0.009) and less likely to receive chemotherapy in the last 30 days of life (34.9% vs. 65.9%, P = 0.008). There was no difference in hospice utilization or hospitalization at the EOL. Conclusions: The integrated palliative and oncology care model for patients with AML receiving intensive chemotherapy led to substantial improvements in patients’ QOL, psychological distress, and EOL care. Thus, palliative care should be considered a new standard of care for patients with AML. Clinical trial information: NCT02975869 .
Effects of YOCAS yoga, cognitive behavioral therapy, and survivorship health education on insomnia: A URCC NCORP Research Base Phase III RCT in 740 cancer survivors.
Authors: Mustian Karen Michelle , Lin Po-Ju , Culakova Eva , Bautista Javier , Xu Huiwen , Mohile Supriya Gupta , Janelsins Michelle Christine , Peppone Luke Joseph , Kleckner Amber , Kleckner Ian , Loh Kah Poh , Dunne Richard Francis , Gilmore Nikesha , Conlin Alison Katherine , Gococo Kim Ong , Jaslowski Anthony John
Published: May 2020

12005

Background: Insomnia, a prevalent and troublesome side effect experienced by cancer survivors, significantly impairs recovery and survival. We conducted a nationwide, multicenter, phase III, blinded, randomized controlled trial testing whether 1) yoga is superior to survivorship health education (SHE) and 2) yoga is non-inferior to cognitive behavioral therapy for insomnia (CBT-I) for treating insomnia in survivors. Methods: The trial was conducted via the University of Rochester Cancer Center NCI Community Oncology Research Program (URCC NCORP) Research Base. Participants were cancer survivors between 2-60 months post adjuvant therapy, with insomnia, no metastatic disease, and no yoga participation during the previous 3 months. Survivors were randomized into 1) YOCAS yoga (2x/wk; 75 min/sess for 4 wks with pranayama, asana, and dhyana, N = 251), 2) CBT-I (1x/wk, 90 min/sess for 8 wks with sleep hygiene, stimulus control, sleep restriction, and cognitive therapy, N = 238), or 3) SHE (2x/wk; 75 min/sess for 4 wks with ASCO-recommended survivorship education, N = 251). Insomnia was assessed pre- and post-intervention via the Insomnia Severity Index. Results: 740 eligible cancer survivors were enrolled (93% female, mean age = 56 + 11, 75% breast cancer). ANCOVAs with baseline values as covariates revealed YOCAS is significantly better than SHE for treating insomnia at post-intervention (CS = change score; CS mean diff = -1.43, SE = 0.42, p < 0.01). Yoga participants demonstrated greater improvements in insomnia from pre- to post-intervention (CS = -3.61, SE = 0.30) compared to SHE participants (CS = -2.19, SE = 0.33, all p < 0.01). Intent-to-treat analyses of non-inferiority (non-inferiority margin set at 1.15 a priori) showed YOCAS is inferior to CBT-I (CS mean diff = 3.52, CI = 2.55 - 4.50, p < 0.01). However, analyses of non-inferiority using the optimal treatment effect in fully compliant survivors were inconclusive regarding whether YOCAS is non-inferior to CBT-I for treating insomnia (CS mean diff = 2.20, CI = 0.42 - 3.98, p = 0.09). Significantly more survivors withdrew from CBT-I and SHE due, in part, to disliking the interventions compared to YOCAS (30%, 25%, and 16%, respectively, p < 0.01). Conclusions: YOCAS yoga is better than SHE and results are inconclusive as to whether yoga is non-inferior to CBT-I for treating insomnia among survivors. Clinicians should consider prescribing YOCAS and CBT-I for survivors reporting insomnia. Funding: NCI UG1CA189961, R01CA181064, T32CA102618. Clinical trial information: NCT02613364 .
Results of crossover phase II component of randomized placebo-controlled trial evaluating oral THC/cannabis extract for refractory chemotherapy-induced nausea and vomiting (CINV).
Authors: Grimison Peter S. , Stockler Martin R. , Kirby Adrienne , Walsh Anna , Lintzeris Nicholas , Cheung Yvonne , Mersiades Antony , Tognela Annette , Haber Paul , Simes John , Morton Rachael L. , Olver Ian N. , McGregor Iain , Gedye Craig , Fox Peter , Briscoe Karen P. , Aghmesheh Morteza , Abdi Ehtesham A. , Clarke Stephen John , Della-Fiorentina Stephen
Published: May 2020

12008

Background: The aim of this multi-centre, randomised, double-blinded, placebo-controlled, phase 2/3 trial is to determine efficacy of addition of oral cannabis in adults with any malignancy of any stage, experiencing CINV during moderate-highly emetogenic intravenous chemotherapy, despite guideline-consistent anti-emetic prophylaxis, requiring ≥ 2 chemotherapy cycles. Here we report the crossover phase 2 component results. Methods: Treatment consisted of 1 cycle of oral THC 2.5mg/CBD 2.5mg (TN-TC11M) capsules tds days -1 to 5 and 1 cycle matching placebo in a crossover design, then blinded patient preference for a 3rd cycle. Primary end-point is difference in proportion of patients with ‘complete response’ (no emesis & no use of rescue medications) during 0-120 hours from chemotherapy between cycles. 80 patients provides 80% power with 2p of 0.1 to detect a 20% difference. Results: 81 patients recruited (2016-9). 72 completing 2 cycles are included in efficacy analyses. 78 not withdrawing consent are included in safety analyses. Median age was 55 years (range 29-80), 78% were female, 42% report historic cannabis use, 55% were treated with curative intent. Most common regimens were AC (26%), FOLFOX (17%). All received steroids & 5-HT3 antagonist, 79% received NK-1 antagonist, 4% received olanzapine. Efficacy is shown in table. 83% preferred cannabis to placebo. Most common bothersome cannabinoid-related adverse events (cannabis, placebo) were sedation (19%,4%), dizziness (10%,1%), disorientation (3%,0%). No SAEs were attributed to THC/CBD. Conclusions: Addition of oral THC/CBD to standard anti-emetics was associated with less nausea & vomiting but additional side effects. Most preferred THC/CBD to placebo. Based on these positive results, the definitive parallel phase 3 trial component continues (additional n=170). Acknowledgements: Trial participants, investigators, research staff. Funding from NSW Government Dept of Health. Clinical trial information: ACTRN12616001036404 . [Table: see text]
Integrated geriatric assessment and treatment (INTEGERATE) in older people with cancer planned for systemic anticancer therapy.
Authors: Soo Wee-Kheng , King Madeleine , Pope Alun , Parente Phillip , Darzins Peteris , Davis Ian D.
Published: May 2020

12011

Background: Older people experience significant adverse effects of cancer and anti-cancer therapy due to age-related vulnerabilities, including medical, functional, cognitive, nutritional and psychosocial issues. Comprehensive geriatric assessment and management (CGAM) provides a powerful framework to assess an older person’s health status and offers a coordinated, person-centered approach to care. Despite its effectiveness, the uptake of CGAM in oncology has been limited due to a lack of randomized evidence in this setting. This study evaluated the effectiveness of CGAM in older people with cancer. Methods: INTEGERATE is a prospective, randomized, parallel group, open-label study in patients aged >70 years with cancer planned for chemotherapy, targeted therapy or immunotherapy. Patients were randomly assigned (1:1) to receive either geriatrician-led CGAM integrated with usual care (integrated oncogeriatric care) or usual care alone, using minimization to balance treatment intent, cancer type, age, sex and performance status. Health-related quality of life (HRQOL) was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-ELD14 at 0, 12, 18 and 24 weeks. The primary outcome was HRQOL measured by the validated Elderly Functional Index (ELFI) score. Major secondary outcomes included function, mood, nutrition, health utility, treatment delivery, healthcare utilization and survival. Results: Of the 154 patients who underwent randomization, 13 died by week 12 and 130 (92.2% of the remaining patients) completed at least two primary outcome assessments. For the primary outcome, patients in the intervention group had significantly better ELFI score than the usual care group across all followup timepoints, with a maximal difference at week 18 (estimated marginal mean ELFI score 72.0 vs 58.7, p= 0.001). In addition, significant differences favoring the intervention group over the usual care group were seen in HRQOL (domains: physical, role and social functioning; mobility, burden of illness and future worries), unplanned hospital admissions (-1.2 admissions per person-years, p< 0.001) and early treatment discontinuation (32.9% vs 53.2%, p = 0.01). Conclusions: Integrated oncogeriatric care led to improvements in HRQOL, unplanned hospital admissions and treatment discontinuation in older people receiving systemic anti-cancer therapy. Older people (>70 years) planned for anti-cancer therapy should receive CGAM to optimize their clinical care and health outcomes. Clinical trial information: ACTRN12614000399695 .
Impact of augmented intelligence (AI) on utilization of palliative care (PC) services in oncology.
Authors: Gajra Ajeet , Zettler Marjorie , Kish Jonathan , Miller Kelly , Frownfelter John , Valley Amy W. , Blau Sibel
Published: May 2020

12015

Background: Timely integration of palliative care in the management of patients with advanced cancer is a quality benchmark in oncology. However, PC is often underutilized as evidenced by delays in identification of appropriate patients, in referrals to a PC service, and in enrollment to hospice. Jvion has developed a prescriptive analytics solution, the Machine, which combines AI algorithms with machine learning techniques and applies them to clinical and exogenous datasets to identify patients with a propensity for poor outcomes. The Machine was applied to risk for patients’ mortality within next 30 days, and recommended patient-specific, dynamic, and actionable insights. Use of the Machine requires no additional documentation within the electronic health record (EHR) and the insights generated can be integrated back in to any EHR to help inform the care plan. Herein, we report the results of a study evaluating the impact of AI-driven insights on PC utilization at a large community oncology practice. Methods: All patients were scored weekly using the Machine PC vector. The Machine risk stratified the patients and generated recommendations for the provider to consider as they developed a care plan. Patients identified as “at risk” by the Machine were assessed for a supportive care visit (PC referral) and then were referred as deemed clinically appropriate. The average monthly rates of PC consults and hospice referrals were calculated 5 months prior to and for 17 months after the launch of the Machine in the practice. Results: The oncology practice has 21 providers managing an average of 4329 unique patients per month (PPM). The mean rate of PC consults increased from 17.3 to 29.1 per 1000 PPM pre and post Machine deployment respectively (+168%). The mean monthly rate of hospice referrals increased by 8-fold from 0.2 to 1.6 per 1000 PPM pre and post deployment respectively. Eliminating the first 6 months of Machine deployment to account for user learning curve, the mean rates of monthly PC consults nearly doubled over baseline to 33.0, and hospice referrals rose 12-fold to 2.4 per 1000 patients in months 7-17 post Machine deployment. Conclusions: This oncology practice found deployment of this novel AI solution to be feasible and effective at generating actionable insights. These AI driven insights could be incorporated into workflow and improved the decision-making for whether and when a patient should be referred to PC and/or hospice services for end of life care. Further study is needed to confirm the value of AI for management of cancer patients at end of life.
Predictive model of aromatase inhibitor non-adherence using patient-reported outcomes in women with breast cancer (SWOG S1105).
Authors: Hershman Dawn L. , Moseley Anna , Arnold Kathryn B , Hillyer Grace , Gralow Julie , Henry N.Lynn , Neugut Alfred I. , Ramsey Scott David , Unger Joseph M.
Published: May 2020

12019

Background: Non-adherence to aromatase inhibitors (AIs) for breast cancer is common and increases risk of recurrence. Few prospective studies have systematically evaluated factors associated with non-adherence. We analyzed baseline sociodemographic, prescription, and patient reported outcome (PRO) symptoms and quality-of-life to identify factors associated with non-adherence prospectively over 3-years. Methods: Patients enrolled in SWOG S1105 were required to have been on an AI for ≥30 days. Patients were assessed for non-adherence to AIs every 3 months for 36 months, with non-adherence defined as urine AI metabolite assay results satisfying any of the following: < 10 ng/mL, undetectable, specimen submitted outside of the ± 21 day follow-up appointment window, or no submitted specimen. At baseline patients were asked about insurance, pill number dispensed and medication cost, and they completed PROs focused on pain and endocrine symptoms (BPI (Brief Pain Inventory), FACT-ES (Endocrine Symptoms)), as well as their beliefs about medications (TSQM (Treatment Satisfaction Questionnaire for Medicine) and BMQ (Brief Medication Questionnaire)). PRO scales were split at the median creating high vs low binary predictors. We determined the association of baseline factors and non-adherence at 36 months. We also evaluated an adverse risk model for AI non-adherence by summing the number of statistically significant adverse factors associated with non-adherence. Logistic regression was used. Results: In total, 724 patients were registered from 40 institutions between May, 2012 and September, 2013. The median age was 60.9 years, and 64.5% were on AI < 12 months prior to registration. Overall, 35.9% were non-adherent at 36 months. Younger patients ( < 65 years) were less adherent (39% vs. 29% non-adherence, OR = 1.51, p = 0.02). Baseline scores on the BPI, FACT-ES, BMQ and TSQM were each statistically significantly associated with AI adherence. Non-adherence was significantly higher among patients scoring poorly on all 4 PRO instruments (65%) compared to those scoring poorly 0 or 1 PRO instruments (27%; OR, 4.68 [2.84-7.73], p < .0001). For each increase in the number of adverse risk PRO scores, the risk of non-adherence increased by 45% (OR = 1.45, p < .0001). Similar results were found when age was included in the score. Conclusions: Presence of multiple baseline risk factors identified through PRO instruments increases non-adherence to AI’s 4-fold. Use of PROs can identify patients for targeted interventions to improve adherence.
Impact of performance status on response and survival among patients receiving checkpoint inhibitors for advanced solid tumors.
Authors: Krishnan Mridula , Teply Benjamin A. , Yu Fang , High Robin
Published: May 2020

12028

Background: Clinical trials leading to the approval of immune checkpoint inhibition (ICI) have almost exclusively been performed in patients with good performance status (ECOG PS of 0-1). However, ICI remains an attractive option for patients with advanced tumors and poor performance status, considering their overall tolerability. While use of ICI in patients with poor PS (ECOG PS of 2 or greater) has been rapidly adopted, whether these patients derive the same benefits as expected in the studied populations is largely unknown. We therefore performed an institutional retrospective analysis of all patients treated with palliative single agent anti-PD1 or anti-PDL1 to determine response and survival for those with poor performance status. Methods: We retrospectively identified patients with advanced solid tumor malignancies who were treated with ICI monotherapy with palliative intent at our institution between 2015-2019. The primary objective was to compare overall survival (OS) for patients with good PS (ECOG PS 0-1) with those with poor PS (ECOG PS 2 or 3-4). The log-rank test compared the survival among patients with different ECOG PS. In addition, we used a proportional hazards model to assess association between ECOG PS and the OS with adjustment for age, gender, and smoking status. A secondary objective was to compare overall response rates (ORR) of the three ECOG PS groups which were evaluated with a binary rate model. Results: We identified 266 patients treated with ICI, 87 with NSCLC, 34 with melanoma, 33 with RCC, 24 with bladder cancer, 22 with head/neck cancer, and the rest with other histologies. 187 (70%) were ECOG PS 0-1, 62 (23%) were ECOG PS 2, and 17 (7%) were ECOG PS 3-4. 89 of these patients (33%) were still alive at time of last follow-up. Across all tumor types, patients with ECOG PS 0-1 had superior survival compared to ECOG PS 2 (median survival 12.4 months vs 4.6 months, HR 0.41, p < 0.001). Median survival for ECOG PS 3-4 was lower at 2.3 months. The ORR for ECOG PS 0-1 (23%) was significantly higher to that of ECOG PS 2 (6%, p = 0.02). ORR for ECOG PS 3-4 was 12%. Conclusions: Despite the appeal of ICI for patients with advanced malignancy and poor performance status, outcomes were poor. Survival and objective response rates for patients with ECOG PS 2 and higher were significantly worse than those with ECOG PS 0-1. ICI treatment comes with cost, including potentially forgoing early hospice referral or optimal support at the end of life. Prospective trials defining the activity and role of ICI in poor PS are urgently needed.
Prospective study comparing self-administered geriatric assessment to provider’s routine clinical assessment of older patients with metastatic breast cancer treated at community oncology practices.
Authors: Seedor Rino S. , Meeker Caitlin R. , Lewis Bianca , Handorf Elizabeth A. , Filchner Kelly A. , Winn Jennifer S. , Goldstein Lori J. , Dotan Efrat
Published: May 2020

12029

Background: Geriatric Assessment (GA) is recommended for evaluating an older cancer patient’s (pt) fitness for treatment. We conducted a prospective study evaluating the current gaps that exist in the assessment of older pts with metastatic breast cancer (MBC) in community practices (CP). Methods: Self-administered validated GA was compared to provider assessment (PA) of MBC pts ≥ 65-years-old treated at CP in the US. Providers were blinded to the GA results until their evaluation was completed. Differences in PA vs GA detected abnormalities were assessed using McNemar’s test. The effect of patient/provider factors on the rate of abnormalities not identified was assessed using regression models, clustering by provider and adjusting for the number of prior pts seen. Results: 100 pts were enrolled across 9 CP (median age 73.9, (65-90)). GA detected a total of 356 abnormalities in 96/100 (96%) pts, of which 223 required immediate interventions. African American and widowed/single pts were more likely to have abnormalities identified by GA. On average PA did not identify abnormalities detected by validated GA in 2 of 8 domains. 73% of functional status, 86% of social support, 44% of nutritional, and 96% of cognitive abnormalities detected by GA were not identified by PA (all P < 0.0001). Providers with more years of clinical experience were more likely to identify abnormalities (compared to < 5 years (y) in practice: 5-10 y in practice, p = 0.149; 11-15 y in practice, p = 0.028; > 15 y in practice, p = 0.017). GA had the most significant impact on pts with decreased ECOG PS (p = 0.045). Pts found to have an abnormal Timed Up and Go (TUG) test were more likely to have additional abnormalities in other domains (mean 4.3 vs 2.1, Wilcoxon p < 0.001), and more abnormalities not identified by the PA (p < 0.001). Providers were “surprised” by GA results in 33% of cases, mainly with cognitive or social support findings, and reported plans for management change for 40% of pts based on GA findings. Conclusions: Including a GA in the care of older pts with MBC in CP is beneficial as validated GA has a high detection rate of abnormalities not detected by PA.
Use of self-rated health to identify frailty and predict mortality in older adults with cancer. Results from the care study.
Authors: Al Obaidi Mustafa , Giri Smith , Mir Nabiel , Kenzik Kelly , McDonald Andrew Michael , Smith Crystal Young , Gbolahan Olumide B. , Paluri Ravi Kumar , Bhatia Smita , Williams Grant Richard
Published: May 2020

12046

Background: Poor self-rated health (SRH) is a known predictor of mortality in the general adult population, but little is known about its use in older adults with cancer. The purpose of this study was to examine the association and ability of SRH to identify frail older adults and assess its ability to predict mortality in older adults with cancer. Methods: Using participants from the Cancer & Aging Resilience Evaluation (CARE) Registry who had undergone a geriatric assessment, we examined SRH using a single-item from the Patient-Reported Outcomes Measurement Information System (PROMIS) global health scale. SRH scores were dichotomized into Poor (poor and fair) and Good (good, very good, and excellent). Multivariable logistic regression analyses were used to examine associations between SRH and frailty (based on frailty index) and specific geriatric impairments adjusting for age, sex, comorbidity, cancer type and stage. Finally, the impact of SRH on all-cause mortality was assessed with a multivariable cox regression model. Results: A total of 708 participants with malignancy were included, median age was 68y, 41.5% male, and 74.6% White. Colorectal cancer was the most common cancer (27.1%) and 48.2% of the participants had Stage IV disease. Poor SRH was reported by 42% of participants and was associated with significantly higher odds of frailty (adjusted Odds Ratio [aOR] = 21.8; 95%CI 13.7-34.8). Similarly, poor SRH was independently associated with higher odds of impairments in Activities of Daily Living (ADL) (aOR = 5.6, 95%CI, 3.6-8.9), independent ADL (aOR = 8.4, 95%CI, 5.8-12.4), cognition (aOR = 4.6, 95%CI 2.3-9.3), malnutrition (aOR = 4.5, 95%CI 3.2-6.4), falls (aOR = 3.6, 95%CI 2.4-5.4), anxiety (aOR = 4.6, 95%CI 2.9-7.3), and depression (aOR = 5.4, 95%CI 3.0-9.7). The SRH demonstrated high sensitivity (84.3%) and specificity (78.4%) for identifying frailty, with a positive predictive value of 67% and negative predictive value of 90.6%. The 1y survival rate in those with Poor SRH was significantly worse (64.7% vs 84.3%, log rank p value < 0.001). In a multivariate cox regression analysis, poor SRH remained an independent predictor of worse survival (adjusted Hazard Ratio 2.29 [1.6-3.2], p< 0.01) after adjusting for age, sex, race, cancer type, stage, comorbidity, and planned treatment. Conclusions: Poor SRH is highly associated with frailty and could be a simple tool to identify frail older patients with cancer at risk for adverse events and increased mortality.
Regaining a satisfactory quality of life and predicting functional decline after major cancer surgery in older adults: The Geriatric Oncology Surgical Assessment and Functional rEcovery after Surgery (GOSAFE) study.
Authors: Montroni Isacco , Ugolini Giampaolo , Saur Nicole , Spinelli Antonino , Rostoft Siri , Ercolani Giorgio , Jaklitsh Michael T. , Van Leeuwen Barbara , de Liguori Carino Nicola , Ferrari Giovanni , Ghignone Federico , Garutti Anna , Di Candido Francesca Rita , Somasundar Ponnandai , Foca Flavia , Vertogen Bernadette , Nanni Oriana , Audisio Riccardo ,   SIOG Surgical Task Force/ESSO GOSAFE Study Group
Published: May 2020

12051

Background: Older cancer patients value quality of life (QoL) and functional outcomes as much as survival but surgical studies lack specific data. The international, multicenter GOSAFE study (ClinicalTrials.gov NCT03299270) aims to evaluate patients’ QoL and functional recovery (FR) after cancer surgery and to assess predictors of FR Methods: GOSAFE prospectively collected functional and clinical data before and after major elective cancer surgery on senior adults (≥70 years). Surgical outcomes were recorded (30, 90, and 180 days post-operatively) with QoL (EQ-5D-3L) and FR (Activities of Daily Living (ADL), Timed Up and Go (TUG) and MiniCog), 26 centers enrolled patients from February 2017 to April 2019. Results: 942 patients underwent a major cancer resection. Median age was 78 (range 70-95); 52.2% males, ASA III-IV 49%. 934 (99%) lived at home, 51% lived alone, and 87% were able to go out. Patients dependent (ADL < 5) were 8%. Frailty was detected by means of G8 ≤14 in 68.8% and fTRST ≥2 in 37% of patients. Major comorbidities (CCI > 6) were reported in 36% and 21% had cognitive impairment according to MiniCog (2.2% self-reported). 25% had > 3 kg weight loss, 27% were hospitalized in the last 90 days, 54% had ≥3 medications (6% none). Postoperative overall morbidity was 39.1% (30 day) and 22.5% (90 day), but Clavien-Dindo III-IV complications were only 13.4% and 6.9% respectively. 30/90/180-day mortality was 3.6/6/8.9% (10/30/33% in patients with severe functional disability). At 3 months after surgery, QoL was stable/improved (mean EQ-5D index 0.78 was equivalent before vs. after surgery, while the EQ-5D VAS score > 60 raised from 74.3% at baseline to 80.2%, p < 0.01). 76.6% experienced postoperative FR/stability. Logistic regression analysis showed that ASA 3-4, CCI≥7 and CD III-IV complications are significantly associated with functional decline while a G8 > 14 has a positive association with functional recovery. Age is not associated with functional outcomes. Conclusions: The largest prospective study on older patients undergoing structured frailty assessment before and after major elective cancer surgery has shown that QoL remains stable/improves after cancer surgery. The majority of patients return to independence and G8 can predict functional recovery. Older patients with multiple comorbidities, high ASA score or postoperative severe complications are likely to functionally deteriorate after oncologic surgery Clinical trial information: NCT03299270 .
The impact of weight loss on physical function in overweight or obese breast cancer survivors.
Authors: Sheng Jennifer Y. , Santa-Maria Cesar Augusto , Blackford Amanda L. , Lim David , Carpenter Ashley , Smith Karen L. , Cohen Gary Irvin , Coughlin Janelle , Appel Lawrence J , Stearns Vered , Snyder Claire Frances
Published: May 2020

12053

Background: In the prospective POWER-remote trial, 51% and 12% of overweight/obese breast cancer survivors randomized to either a remotely delivered behavioral intervention or self-directed approach, respectively, lost ≥5% of baseline weight. We collected patient-reported outcomes (PROs) to examine the impact of >5% weight loss on symptoms, physical function (PF), and wellbeing. We hypothesized a priori that, regardless of study arm, those with ≥5% weight loss would have improved PF at 6 months v. those who did not. Methods: Women with stage 0-III breast cancer, who completed local therapy and chemotherapy, with a BMI ≥25 kg/m2 were randomized to the 12-month intervention or self-directed weight loss. POWER-remote consists of telephone coaching and online tracking of diet, activity and weight. Women in the self-directed arm received a lifestyle booklet. All women completed PROs at baseline, 6 and 12 months: PROMIS PF, pain, fatigue, anxiety, depression, sleep; FACT-endocrine symptoms; MOS-sexual function. PROs were summarized descriptively and changes within and between groups were tested with multivariable mixed effects models, adjusted for age and baseline weight. Results: From 2013-2015, 96 women enrolled; 83 were evaluable at 6 months. At 6 months, PF scores improved in those with ≥5% weight loss v. not. While endocrine symptoms, fatigue, and anxiety improved in the group who lost ≥5%, differences between groups were not statistically significant. There was no significant change in sexual function, depression, or sleep within or between groups. Similar findings were seen across domains at 12 months, except pain improved in the group losing ≥5%. Conclusions: For overweight/obese breast cancer survivors, PF and other PROs improved among patients who lost ≥5%. These results support the patient-centered benefits of weight loss in this population. Clinical trial information: NCT01871116 . [Table: see text]
Patterns of the risk for subsequent primary cancer among survivors of adult-onset cancers in the United States.
Authors: Sung Hyuna , Hyun Noorie , Yabroff K Robin , Jemal Ahmedin
Published: May 2020

12060

Background: The number of cancer survivors who develop new cancers is projected to grow in the US. Few studies, however, have provided a comprehensive overview of the contemporary pattern in the risk of subsequent primary cancer (SPC) among survivors of adult-onset cancers. Herein, we evaluate overall and type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer types and sex. Methods: We assessed the excess risk of SPCs among 1,442,374 persons aged 20-84 years who were diagnosed with first primary cancers from 1992-2010 and survived ≥5 years in the 12 Surveillance, Epidemiology, and End Results registries. We expressed the risks using excess absolute risk (EAR) per 10,000 person-years and standardized incidence ratio (SIR) by first primary cancer types and sex, compared to those expected in the general population. We also estimated percent contributions of each specific type of SPCs to the total EAR for all first primary cancers combined by sex. Results: The overall risk of SPCs was higher than expected for 24 of the 34 first primary types among male survivors and for 28 of the 35 first primary types among female survivors. The greatest SIR and EAR were estimated after laryngeal cancer in both men (SIR = 1.74, 95%CI = 1.67-1.82; EAR = 159.3, 95%CI = 143.6-175.5) and women (SIR = 2.48, 95% CI = 2.26-2.73; EAR = 202.7; 95%CI = 171.8-236). There were 290 type-specific associations with significantly higher risk of SPC, 36% of which being reciprocal, predominantly among smoking-associated, HPV-associated, and hematologic cancers. The SIRs in men ranged from 1.05 (95%CI = 1.00-1.10; EAR = 1.69) for lung/bronchus cancer after colorectal cancer to 73.9 (95%CI = 58.3-92.3; EAR = 23.3) for anal cancer after Kaposi sarcoma; and in women the SIRs ranged from 1.08 (95%CI = 1.02-1.15; EAR = 0.36) for pancreatic cancer after breast cancer to 19.9 (95%CI = 15.0-26.0; EAR = 39.5) for oral cavity/pharyngeal cancer after laryngeal cancer. For all first primary cancers combined, lung/bronchus cancer comprised the greatest proportion of the total EAR of SPCs, 34.6% in men and 29.1% in women, followed by urinary bladder (11.8%) and oral cavity/pharynx (7.5%) in men and by corpus uterus (12.9%) and colorectum (7.6%) in women. Conclusions: Despite the substantial heterogeneity in the risk of SPCs across the first primary types, only a few cancers comprised a considerable proportion of the total excess risk among survivors. Better understanding of contributing factors to these patterns will inform survivorship care plans and care delivery.
Fatigue in long-term survivors with ovarian cancer: Results of Expression VI – Carolin meets HANNA – Holistic analysis of Long-term survival with ovarian cancer—The international NOGGO, ENGOT and GCIG survey.
Authors: Woopen Hannah , Keller Maren , Braicu Elena Ioana , Zocholl Dario , Krabisch Petra , Boxler Tamara , Barretina-Ginesta Maria Pilar , Mendiola Cesar , Lafleur Judith , Reimer Daniel Uwe , Heinzelmann-Schwarz Viola A. , Samartzis Eleftherios Pierre , Vardar Mehmet Ali , Taskiran Cagatay , Vergote Ignace , Van Nieuwenhuysen Els , Sehouli Jalid
Published: May 2020

12065

Background: Long-term survivors (LTS) with ovarian cancer may be cured from cancer but frequently experience long-term toxicities such as fatigue with a huge impact on quality of life. Aim of this study was to evaluate factors associated with fatigue in LTS. Methods: Within the study “Carolin meets HANNA” ( www.carolinmeetshanna.com ) long-term survivors with ovarian cancer (LTS) were recruited since 11/2016. Long-term survival was defined as an ovarian cancer diagnosis more than eight years ago. Results: Until 12/2019 473 LTS could be recruited. 211 LTS (44.5%) have experienced fatigue. At the time point of recruitment in 23.4% (111 LTS) fatigue was still present. LTS with fatigue were not more frequently under current treatment compared to LTS without fatigue (p = 0.348). LTS with fatigue were not younger at initial diagnosis (50.4 vs. 51.9 years, p = 0.228). 58.6% of LTS with fatigue compared to 41.5% without fatigue have developed recurrent disease (p = 0.002) and LTS had more frequently more than one recurrence (66.1% vs. 51.7%, p = 0.055). Fatigue was associated with worse health status (2.9 vs. 2.2 on a scale from 1-5, p < 0.001). Fatigue was associated with medical complaints in general (82.0% vs. 43.0%, p < 0.001). Symptoms such as nausea and vomiting (p < 0.001), loss of appetite (p < 0.001), constipation (p < 0.001), diarrhea (p < 0.001), weight loss (p = 0.001) and bloating (p < 0.001) were more frequent in LTS with fatigue. This also accounts for cognitive disorders (39.6% vs. 10.5%, p < 0.001), depression (23.4% vs. 7.4%, p < 0.001), polyneuropathy (39.6% vs. 13.2%, p < 0.001) and cardiovascular disease (11.7% vs. 3.6%, p = 0.002). LTS with fatigue regard themselves more frequently as cancer patient (73.9% vs. 40.8%), p < 0.001). Conclusions: Fatigue is still very common in LTS despite the long survival time. Fatigue is associated with worsened health status and other long-term side effects underlining the impact on LTS. There is a high need for survivorship clinics that should ask for and, if necessary, should address still existing side effects such as fatigue.