bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of inpatient palliative care consultation for patients with brain and spine metastases.
Authors: Howell Elizabeth , Price Meghan , Dalton Tara , Williamson Theresa , Kamal Arif , Goodwin Rory
Published: May 2020

e24117

Background: Patients diagnosed with brain and/or spine metastases (BSM) face high symptom burden and complex clinical decision-making. Through expertise in pain and symptom management, facilitation of end-of-life planning, and caregiver support, specialty Palliative Care (PC) can provide a crucial component of the care for these patients. No prior study has formally evaluated the rates of inpatient PC referral in BSM patients, nor the patient-specific factors that may affect consultation rates within this context. Methods: Analysis was performed of the rates of PC consults in a cohort of BSM inpatients admitted to three tertiary medical centers: one major academic center and two smaller affiliate centers. Patients were identified using a combination of ICD-9 and -10 codes and surgical provider lists to aggregate brain and spine metastases patient cohorts at each institution. Patient demographics, surgical status, and readmission data were collected. PC utilization was assessed by flagging encounters within which an inpatient consult to PC was placed. Results: 2608 total discharges were analyzed, with 2397 brain metastasis and 301 spine metastasis discharges. Average rate of inpatient PC consultation over the 3.5 year study period was 13.6% for brain metastasis patients and 11.0% for spine metastases patients. Rates of PC utilization differed significantly by patient race (11.6% in white vs. 17.0% in non-white patients, p = 0.02). Patients who received surgery had significantly lower rates of PC consultation in both brain (3.5% vs 15.6%, p < 0.001) and spine (5.5% vs 14.1% p < 0.001) cohorts. The large academic center had the lowest utilization as compared to two smaller affiliate centers, with 6.4% of brain and 7.6% of spine metastasis patients receiving PC consults. For both cohorts, Neurology was the discharging service with the highest rates of PC utilization, consulting PC for 37.7% of brain and 42.9% of spine metastasis patients respectively. Over time, PC utilization increased for brain, but not spine, metastasis patients. Conclusions: Despite their high symptom burden and low overall survival, BSM patients have low rates of inpatient PC consultation. Utilization appears to vary by patient demographics and surgical status, as well as discharging service and practice setting. These single-institution patterns may ultimately provide a microcosm for national patterns and trends at similar institutions, and further work is needed to identify the specific barriers to optimally utilizing specialty PC in this population.
Early referral to palliative care: Where are we in Brazil?
Authors: Santos Andre Filipe Junqueira , Monteiro Aurélio , Duarte Carolina Sarmento , Silva Carolina Gomes Jacobina , Gomes Sarah Ananda , Vieira Clarissa Miranda
Published: May 2020

e24118

Background: The American Society of Clinical Oncology (ASCO) recommends that patients with advanced cancer receive dedicated palliative care services concurrently with active treatment within 8 weeks of diagnosis and maintaining follow up for at least 12 weeks. The adherence to these standards in Brazil is unknown. Objective: To evaluate adherence to ASCO recommendations of early referral to a palliative care team at a multicentric outpatient oncological clinic in Brazil using the following indicators: (i) whether patients were enrolled in palliative care services within 8 weeks of diagnosis and (ii) whether patients were followed up for a minimum of 12 weeks. Methods: All palliative care physicians within a network of 15 outpatient oncology clinics (Oncoclinicas Group) prospectively recorded time to care post-diagnosis with advanced cancer by ASCO guidelines and duration of follow up time throughout the 1-year duration of the study. The number of patients enrolled in care within 8 weeks of diagnosis and followed for at least 12 weeks was recorded. An initial goal of adherence was set at 50% for each indicator. Results: Of 1016 patients, we studied 579 data numbers. 26% of patients were referred within 8 weeks of their advanced cancer diagnosis and 23% were followed for 12 weeks or more. Conclusions: These data indicate that even with a recognition of ASCO recommendations for timely palliative care referral, patients in Brazil are often seeing palliative care teams too late. The possible main causes of this late referral in Brazil are: (i) lack of adequate knowledge about the real meaning of palliative care and (ii) a lack of understanding of how a multidisciplinary team acts positively in the patient's experience. We believe that the best way to change this reality is through continuing education about Palliative Care, reinforcing the intention of continuous care: strengthening bonds, facilitating communication, reaching better symptoms control and practicing patient-centered care.
Changes in physical activity from pre-diagnosis to first five years post-diagnosis: A prospective cohort study in Chinese breast cancer patient.
Authors: Lei Yuanyuan , Yeo Winnie , Ho Suzanne C. , Cheng Ashley Chi Kin , Kwok Carol
Published: May 2020

e24121

Background: The diagnosis of cancer can motivate patients to change their physical activity habits. No data has reported level of physical activity before and after breast cancer diagnosis in Chinese women. Methods: In an on-going prospective cohort study which involved 1462 Chinese women with early-stage breast cancer, a validated modified Chinese Baecke questionnaire was used to assess physical activity at baseline, 18-, 36- and 60-month after diagnosis. At baseline, patients recalled their habitual physical activity in the preceding 12 months before cancer diagnosis. At 18-, 36- and 60-month follow-up, patients reported their habitual physical activity over the previous 12 months. The level of physical activity at post-diagnosis was defined as the average value assessed at 18-, 36- and 60-month follow-up. Results: Breast cancer patients significantly increased level of physical activity, with median value of 0.6, 5.3, 4.4 and 3.9 MET-hours/week at baseline, 18-, 36- and 60-month follow-up. The average level of physical activity at post-diagnosis was also significantly higher than that at pre-diagnosis ( P < 0.001), with median value of 5.8 MET-hours/week. However, there was no significant difference between any two follow-ups at post-diagnosis. The proportions of participant who met the exercise recommendation (according to WCRF/AICR, 10 MET-hours/week) were low at pre- and post-diagnosis, being 20.7% and 35.1%, respectively. Compared to pre-diagnosis, most of the patients improved or had no change on level of recreational physical activity at post-diagnosis, with the respective proportion being 48.2% and 43.8%. Multivariate analysis showed that higher increase in physical activity after cancer diagnosis was observed among breast cancer patients who were married or cohabitation, unemployed (compared to full time) and had no comorbidity (compared to patients who had one comorbidity). Conclusions: Chinese breast cancer patients reported significant and long-term changes in physical activity after cancer diagnosis, which was in line with current recommendation. However, the proportion of patients who met the exercise recommendation for cancer survivors was still low. Empowering patients on the importance of durable high level of physical activity in breast cancer survivorship is warranted.
Developing survivorship services in Ghana and Tanzania.
Authors: Dharsee Nazima Jaffer , Addai Beatrice W , Murray Lisa , Shewbridge Amanda , Aresu Maria , Stanway Susannah Jane , Small Sheila , o'Gara Geraldine , Wiafe Seth A , Wiseman Theresa
Published: May 2020

e24132

Background: The incidence of breast cancer is increasing in low- & middle- income countries (LMICs). Alongside attempts to reduce the disparity in cancer survival between high-income countries (HIC) & LMICs, it is important that survivorship is well understood and managed in an evidence based, resource and culturally sensitive manner. This project aimed to develop knowledge, skills and services concerning living with and beyond breast cancer primary treatment. Methods: This 3-phase study used mixed methods. Phase 1 used participant observation and focus group interviews (FGIs) to scope experience, resources, current practice, and challenges to implementing a recovery package. In Phase 2 nurses used the adapted Holistic Needs Assessment (HNA) with 500 women in Tanzania and Ghana, who were also offered a recovery care plan and treatment summary following their breast cancer primary treatment. Data was entered into a macro database & analysed using descriptive statistics. Phase 3 was the development of a culturally sensitive “Foundations in Cancer Care” training toolkit for nurses. The toolkit was based on a “train the trainer” model and included slides, an existing palliative care toolkit and exercises. The training programme consisted of 5 days teaching covering theory and practice. Data collection included: Initial FGIs to ascertain learning needs, confidence in knowledge & skills, assessed pre & post teaching course, and course evaluation. Data were analysed using descriptive statistics. Results: In Phase 1 six themes were identified concerning experience of breast cancer which included cultural beliefs & practices and access to treatment & support. Phase 2 data from Tanzania showed a similar level of unmet need at the end of treatment to a previous similar published analysis from the UK. Data from Ghana showed a much higher level of unmet need. Evaluation following Phase 3 showed a positive change in nurses’ confidence in their knowledge. Conclusions: This mixed methods three-phase study has documented experience, resources and current practise around breast cancer survivorship in two African centers treating breast cancer. The feasibility of using HNA to identify unmet needs in these women has been demonstrated and needs the identified. Results from the HNA informed a training toolkit which was implemented and positively received and could be adapted for use in other LMICs.
Growth differentiation factor 15 (GDF-15) as a key regulator of cachexia induced by platinum-based chemotherapy.
Authors: Breen Danna , Beaumont Kevin , Bennett Donald , Brosnan Julia , Calle Roberto A , Chabot Jeffrey , Collins Susie , Esquejo Ryan , Joaquim Stephanie , Joyce Alison , Kim Hanna , Lin Laura , Pettersen Betty A , Qiao Shuxi , Rossulek Michelle I , Walters Karen , Weber Gregory , Wu Zhidan , Zhang Bei Betty , Birnbaum Morris J
Published: May 2020

e24162

Background: Platinum-based drug use in cancer treatment is restricted by dose-limiting side effects, including nausea/emesis, anorexia and weight loss that reduce patient quality of life and limit treatment adherence. Cisplatin increases GDF-15, a cytokine that induces aversion, anorexia and weight loss in preclinical models. GDF-15 signals through the hindbrain receptor glial cell-derived neurotrophic factor receptor alpha-like (GFRAL) and cisplatin-induced weight loss was attenuated in a GFRAL knockout mouse. Methods: In the current study, using mouse and/or nonhuman primate models, we examined whether GDF-15 inhibition via a potent and selective monoclonal antibody (mAB1) prevents platinum-induced emesis, anorexia, weight loss, with increased survival. Results: Circulating GDF-15 levels in NSCLC and colorectal cancer were higher (~1.5 fold) in patients on platinum therapy compared to non-platinum-based therapy. Higher levels of circulating GDF-15 were also associated with greater weight loss in colorectal cancer patients prior to receiving FOLFOX as part of cancer treatment. In wildtype mice, cisplatin, oxaliplatin and carboplatin each increased circulating GDF-15 (≥ 5-fold) and induced anorexia, skeletal muscle wasting, and weight loss. These effects were prevented in GDF-15 knockout mice, however only a partial blockade of carboplatin was observed. The GDF-15 neutralizing efficacy of mAB1 was confirmed by reversing AAV-GDF-15-induced weight loss in wildtype mice. In nonhuman primates, cisplatin treatment for 5 days (96% of the daily recommended clinical dose) also increased circulating GDF-15 ( > 5-fold), and induced anorexia and emesis. Treatment with mAB1 resulted in no detectable circulating levels of free GDF-15 and attenuated both cisplatin-induced anorexia and emesis. In a mouse cachectic tumor model (subcutaneous; NSCLC patient derived xenograft), cisplatin inhibited tumor growth; however, GDF-15 levels remained elevated and additional weight loss occurred compared to control. When mAB1 was given in combination with cisplatin, weight loss was reversed and tumor growth inhibition was maintained, resulting in greater survival compared to cisplatin alone. Conclusions: Taken together, these data support that GDF-15 inhibition with mAB1 holds the potential as an effective therapeutic approach to alleviate GDF-15 mediated emesis, anorexia and weight loss, with the aim to enable optimal cancer treatment as well as to improve patient quality of life and potentially survival.
Pastoral care of cancer patients: Defining utilization of services at a comprehensive cancer center.
Authors: Palmer Elizabeth , Paredes Anghela , Hyer Madison , Pawlik Timothy M.
Published: May 2020

e24171

Background: Addressing the religious/spiritual needs of patients is an important component of comprehensive cancer care. Patients often report that providers infrequently engage them about their needs during treatment. In addition, providers cite inadequate training as a significant barrier to providing spiritual care. While patients may benefit from the presence of a spiritual care specialist during cancer treatment, the utilization and content of these services are not well defined. We sought to characterize utilization of pastoral care (PC) services, as well as delineate differences in PC utilization among patients with cancer. Methods: Data on patients being treated for cancer at a Comprehensive Cancer Center between 2015-2018 were obtained from the electronic medical record. Overall utilization, type of PC services utilized, as well as factors associated with use of PC were assessed. Analyses included descriptive statistics and logistic regression. Results: Among 14,322 cancer patients, roughly one-third (n = 5166, 36.1%) had at least one PC encounter during their cancer treatment. Interventions most frequently provided by PC included supportive presence (93.5%) and active listening (86.6%), while the most frequently explored topics were treatment expectations (59.8%), issues with faith/beliefs (42.9%), and available coping mechanisms (35.4%). Patients diagnosed with colorectal (OR:1.42, 95%CI:1.07-1.89), liver (OR:2.41, 95%CI:1.80-3.24), or pancreatic cancer (OR:1.43, 95%CI:1.02-2.00) were more likely to utilize PC services compared with other cancers. Patients that identified as Catholic (OR:1.47, 95%CI:1.17-1.84) or Christian (OR:1.73, 95%CI:1.39-2.15) were more likely to request PC services (both p < 0.001) than individuals who had no religious preference/affiliation. Among surgical patients (n = 1,174), the majority of encounters with PC services were in the postoperative setting (n = 801, 70.6%). Patients most often reported that PC helped with verbalization of their feelings (93.6%) and helped reduce stress (76.9%). Conclusions: Over one-third of patients with cancer interacted with PC and received services that often addressed both psychosocial and spiritual concerns. Overall PC utilization and types of PC services rendered varied relative to demographic and religious factors. Providers should be aware of varying patient religious/spiritual needs so as to optimize the entire cancer care experience for patients.
Delay discounting as a predictor of adjuvant endocrine therapy adherence among breast cancer survivors.
Authors: Vaughn Jennifer , Ammerman Chesley , Stein Jeffrey
Published: May 2020

e24172

Background: Despite the demonstrated mortality benefit, 30-70% of hormone-responsive breast cancer (BC) survivors struggle to adhere to adjuvant endocrine therapy (ET). Little is known about patient-specific behavioral traits and their role in ET non-adherence. To gain a survival benefit, patients must adhere to ET for years. In contrast, the benefits of discontinuing ET (i.e., avoiding toxicity) are immediate. Thus, adherence requires one’s behavior to be guided by future outcomes, rather than immediate gratification. We therefore hypothesized that ET adherence may be related to the behavioral economic process of delay discounting (DD; i.e. devaluation of delayed outcomes), which provides a measure of how individuals value the future. Methods: BC survivors (age 18-80) prescribed adjuvant ET within the last 5 years were recruited. ET adherence was measured by pill count and self-report. DD was measured using two methods: monetary DD was measured using a validated task in which participants made repeated, hypothetical choices between a larger amount ($100 or $1000) available after a time delay or half of this amount ($50 or $500) available now. Across trials, the delay to the larger amount is titrated based on previous choices until reaching a delay at which the participant becomes indifferent to waiting for the larger reward. Cancer DD was measured using an investigational task adapted from the adjusting-delay task described above. This task presented repeated, hypothetical choices between preventing BC recurrence after varying time delays and avoiding ET side effects immediately. Results: Eighty nine BC survivors participated. Average pill count adherence was near 50%, but self-reported adherence was near 100%. Monetary DD was significantly associated with pill counts; adherence improved with increasing log indifference delays (standardized b 0.328, p = 0.005). Self-report adherence (categorized as discontinued/never started, suboptimal, and perfect) was significantly associated with Cancer DD and income (OR 3.764, p < 0.001 and OR 1.01, p = 0.04, respectively) but not monetary DD (OR 0.978, p = 0.951). No association was found between ET non-adherence and medication type, side effect severity, menopausal status, age, education or minority status. Conclusions: DD may promote ET non-adherence among BC survivors. Behavioral therapies which reduce DD may provide a targeted strategy to improve adherence. More research is needed to develop tools that reliably assess ET adherence and that tailor DD assessments to the cancer survivor population.
Surviving metastatic non-small cell lung cancer (mNSCLC): The lived experience and supportive care needs of patients (pts) receiving immunotherapy (IT) or targeted therapy (TT).
Authors: Lai-Kwon Julia Elizabeth , Heynemann Sarah , Flore Jacinthe , Duffy Mary , Kokanovic Renata , Jefford Michael
Published: May 2020

e24185

Background: IT and TT have improved survival for many pts with mNSCLC. However, the lived experience of these pts is under-studied. We conducted a single centre, qualitative study to understand concerns and supportive care needs of this novel survivor population. Methods: Eligible pts had mNSCLC, aged >18, English speaking and > 6 months post initiation of IT/TT without progressive disease. Semi-structured interviews were conducted focusing on physical, psychological, social and functional impacts of diagnosis, therapy and prognosis. Interviews were audio-recorded and transcribed. The framework method of analysis was used. Results: 20 pts were interviewed between May-December 2019; median age 62 years (range 34-83), 13 (65%) female; median time since diagnosis of mNSCLC 27 months (range 10-108). 12/20 (60%) had tumours with a targetable molecular alteration (EGFR/ALK/BRAF). 6 were receiving IT, 11 TT, 2 IT and chemotherapy, 1 IT and TT. Dominant themes included: the experience of chronic toxicities (cutaneous, gastrointestinal, fatigue); psychological concerns (living with uncertainty, fear of cancer progression [FCP], scan-related anxiety, stigma around smoking, loneliness) and coping strategies (living in the present, practising self-care with exercise and meditation, early discussions with their treating team regarding future treatment options, and accessing psychology services); the desire for tailored information (internet resources, support groups, challenges in accessing pertinent information); and the desire for assistance with practical issues (financial planning, returning to work, challenges of long-term clinical trial participation, difficulty planning for the future). Conclusions: Longer term survivors of mNSCLC report significant physical, psychological and functional concerns and unmet needs. Self-management strategies for chronic toxicities, professional psychological services to manage FCP and scan-related anxiety, and tailored information regarding work and financial planning may mitigate these concerns. Future work should examine these issues in a larger population.
Understanding therapy preferences of cancer patients with the use of therapy preference scale.
Authors: Dhakal Prajwal , Wichman Christopher S , Pozehl Bunny J , Vose Julie , Bociek Gregory , Bhatt Vijaya Raj
Published: May 2020

e24186

Background: Patients’ (pts) preferences, crucial in selecting an appropriate treatment (tx), are understudied in cancer pts. We developed a novel self-reported questionnaire “Therapy Preference Scale” (TPS) (J Geriatr Oncol. 2019:677-679, J Clin Oncol 2019 37: e23179-e23179). Our single-center prospective observational study utilized TPS to gain in-depth understanding of pts’ preferences of various aspects of cancer tx. Methods: Eligible pts were adults aged ≥19 y with a diagnosis of cancer. Pts were asked to complete TPS; this 30-item scale captures pts’ rating of the importance of safety, efficacy and other characteristics of cancer tx (on a scale of 0-10), and importance of one over the other aspects of tx (using a 4-item Likert scale). Demographics, cancer-specific and therapy-related data were collected. Descriptive statistics were used for analysis. Results: Total 100 pts were enrolled- 52% were receiving cancer tx; 40% had completed tx; 8% were newly diagnosed and had not yet started tx. Pts were willing to accept short term SE for increased life expectancy but valued maintenance of cognition, functional ability and QoL. 70% valued maintaining cognition, functional ability and quality of life (QoL) than increased life expectancy; 75% would accept cancer tx if it improved QoL but 88% would reject a harsh tx for improved life expectancy of ≤6 months. Conclusions: Avoiding long term side effects (SE), life threatening infections, tx burden and financial toxicity were most important to pts. Harsh tx with ≤6 months improvement of life was unacceptable. These findings will help physicians understand pt preferences and guide selection of tx that will meet pts’ goals of care, and may also have implications for insurance policies and drug approval. [Table: see text]
Communicating cancer and its treatment to Australian Aboriginal patients with cancer: A qualitative study.
Authors: Olver Ian N. , Gunn Kate M , Knott Vikki E , Chong Alwin , Spronk Kristiaan , Cunningham Joan
Published: May 2020

e24188

Background: To enable clinicians to effectively communicate about cancer and its treatment to Aboriginal and Torres Strait (Aboriginal) people with cancer who need to make informed choices about the Western medicine offered, we sought strategies from health professionals with experience in that field. Methods: Semi-structured interviews were conducted face-to face or via telephone with the experienced health professionals and audio-recorded. Thematic analysis using a bottom up, essentialist/realist approach was employed to analyse the data, when data saturation was reached. Results: The 23 health professionals interviewed were medical and radiation oncologists, oncology nurses and Aboriginal health workers. Twelve were female, 11 were male with 5 identifying as Aboriginal. Six themes emerged. (1) Create a safe environment, engender trust and build rapport. This involves avoiding assumptions, allowing time, considering the physical environment, asking about home and family, being aware of gender issues and noting non-verbals. (2) Employ specific strategies to explain cancer, treatment and its side effects by using simple language, employing visual aids such as drawings, metaphors and relatable analogies such as trees with roots, weeds, abandoned rusty cars and blocked pipes. Use repetition and ensure alignment with patient needs. Warning about upcoming sensitive issues minimised the chance of disengagement. (3) Obtain support from those who can assist in communication. This includes interpreters, aboriginal liaison officers and health workers, and patient escorts. (4) Consider the culture which involves collective decision-making, strong connection to country and community, with cultural obligations and unique understanding of cancer which can involve curses, shame and utilise bush medicine. (5) Develop personal qualities of good communicators, including showing respect, patience, empathy, honesty, being person centred and embracing personal reflection. (6) Understand the contextual complexity of multiple languages, possible disengagement with treatment, difficulty maintaining contact with patients, conflicts between Western medicine and Aboriginal culture and late stage presentations. Be aware of practitioner bias. Conclusions: These insights will help foster more positive interactions with the health system and promote optimal outcomes for Aboriginal people with cancer and enable the creation of educational modules for inexperienced clinicians.
S1801: A randomized phase II trial of adjuvant versus neoadjuvant pembrolizumab (PEM) for melanoma.
Authors: Patel Sapna Pradyuman , Othus Megan , Moon James , Tetzlaff Michael T. , Buchbinder Elizabeth Iannotti , Sondak Vernon K. , Lowe Michael C. , Campos Danae , Sharon Elad , Korde Larissa A. , Carson William Edgar , Ribas Antoni , Grossmann Kenneth F.
Published: May 2020

TPS10090

Background: Although long term outcomes for most patients with early-stage melanoma is excellent following surgery, patients who have high-risk features such as lymph node involvement have poorer outcomes. Adjuvant therapy (AT) is currently considered for patients with stage III melanoma and selected patients with resected stage IV melanoma. Currently, AT for melanoma is anti-PD-1 or targeted therapy in the presence of a BRAF mutation. At this time we are not able to predict which patients will derive benefit from AT and experience cure. While curative surgery is the goal of early treatment of primary melanoma, some cases with bulky nodal involvement are at high risk of local or distant recurrence despite upfront surgery. Neoadjuvant treatment (NAT) offers the benefit of an early on-treatment pathological sample that can be profiled for biomarkers and correlated with survival. Treating with anti-PD1 while tumor transiently remains in the body may generate a stronger immune response from tumor-infiltrating lymphocytes against in vivo tumor antigens compared to the traditional adjuvant setting where antigen is presented by microscopic residual tumor burden. Pilot studies using NAT with have been initiated in melanoma. Multidisciplinary coordination in these cases is paramount. In these studies, an improvement in relapse-free survival and overall survival has been observed; additionally, pathologic response rates to NAT have been estimated in small studies. Methods: S1801 is a randomized phase II study of AT versus NAT with PEM (NCT03698019). Patients with measurable, clinically detectable and resectable cutaneous, acral, and mucosal melanomas without brain metastasis are eligible. Patients are randomized 1:1 to the AT or the NAT. Patients getting AT receive surgery first followed by 18 doses of PEM 200 mg IV every 3 weeks. Patients getting NAT receive 3 doses of pre-operative PEM followed by surgery and then 15 doses of adjuvant PEM. Radiation may be given on either arm after surgery, at the investigator’s discretion. Primary endpoint is event-free survival measured from the date of randomization to the date of first documented progression that renders the patient unable to receive planned protocol surgery, failure to begin AT within 84 days of surgery, relapse after surgery, or death due to any cause. Safety monitoring is conducted with disease progression and toxicity thresholds. The key Translational Medicine objective of this trial is to determine the pathologic response rate to NAT with 3 doses of PEM. Enrollment is at 94 of a planned 500 patients. Clinical trial information: NCT03698019.
A phase I dose-escalation trial of alpha-tocopheryloxyacetic acid and concurrent trastuzumab in patients with treatment refractory HER2+ metastatic breast cancer.
Authors: Gwin William R , Childs Jennifer , Higgins Doreen , Burton Kellie Ann , Kuano Kristin , Corulli Lauren , Dai James , Akporiaye Emmanuel T , Disis Mary L.
Published: May 2020

TPS1103

Background: Metastatic HER2+ breast cancer, while initially responsive to trastuzumab, pertuzumab, and TDM-1, eventually progresses. The FDA recently approved trastuzumab deruxtecan, showing benefit in progression free survival but not in overall survival to date. Thus, additional therapies are needed for patients who progress on these HER2 directed agents. In metastatic HER2+ breast cancer, HER2-specific Th1 immune responses and higher CD4+ Th1 and CD8+ TIL levels are associated with a survival benefit. As this Type 1 immunity occurs in a minority of patients, additional immune modulation is needed. Alpha-tocopheryloxyacetic acid (α-TEA) has been reported to augment Type 1 immunity through increasing activated effector memory CD4+ and CD8+ T cells and decreasing immune suppressive CD4+CD25+ regulatory T cells in the tumor microenvironment. When given concurrently with an anti-HER2 antibody (7.16.4) in a pre-clinical tumor model, α-TEA synergized with 7.16.4 to induce tumor regression. We hypothesize that α-TEA and trastuzumab combination therapy in metastatic HER2+ breast cancer will be well tolerated, induce a clinical response, and augment anti-tumor Th1 immunity. Methods: Trial Design: Phase I dose escalation trial of α-TEA in combination with trastuzumab. Patients with metastatic HER2+ breast cancer will receive one of four doses sequentially of α-TEA: 0.6 mg/kg, 1.2 mg/kg, 2.4 mg/kg, and 4.8 mg/kg. Toxicity is assessed at baseline and through end of study. Blood and tumor tissue will be collected for immunologic monitoring and evaluation. Clinical response will be evaluated according to RECIST 1.1. Eligibility : Patients with progressive metastatic HER2+ breast cancer who have previously progressed on trastuzumab/pertuzumab and TDM-1. Specific Aims: Determine: (1) safety of four escalating doses of α-TEA with concurrent trastuzumab, (2) clinical response rate of α-TEA with concurrent trastuzumab (3) if concurrent α-TEA and trastuzumab increases activated effector memory CD4+ and CD8+ T cells, and (4) if concurrent α-TEA and trastuzumab increase the number of HER2-specific T cells. Statistical Methods: (1) The sample size of 24 and cohort size of 6 are determined by simulation experiments and practical consideration, (2) clinical response will be evaluated; overall PFS and OS will be calculated, (3) activated effector memory CD4+ and CD8+ T-cells will be analyzed (4) HER2-specific IFN-g/IL-10 ratios will be evaluated. Targeted Accrual : Twenty-four (24) patients. Clinical trial information: NCT04120246 .
Building resilient oncologists: A feasibility study of a resiliency curriculum for hematology oncology fellows.
Authors: Chatwal Monica Sheila , Vinci Christine , Reich Richard R. , Boulware David C. , Fan Wenyi , Reagan Angela , Gray Jhanelle Elaine
Published: May 2020

TPS11043

Background: Rates of burnout and career dissatisfaction have declined slightly, but remain high among oncologists (Berg, AMA 2020). As hematology oncology fellows prepare to join this workforce, the ACGME now mandates wellness be a part of their training curriculum. Yet, there are few, if any, structured and effective programs specifically for these trainees. Based on feedback from our prior mindfulness-based wellness curriculum, we created a more varied and comprehensive resiliency program with the use of our institutional resources to incorporate and evaluate as part of our fellowship curriculum (ASCO, Abstract 10508), and potentially expand to other fellowships. Methods: This is a single-center, non-randomized, pilot project to assess the feasibility, acceptability, and impact of a resiliency training program. All hematology oncology fellows at our institution were eligible for enrollment, and participation was voluntary. A total of seven monthly, 1 hour sessions were conducted through the academic year. Each session focused on a particular topic - alternative forms of wellness through art and music, self care, mindfulness and stretching, reflective writing, and healthy boundaries and work life integration - which have all been studied individually in wellness and burnout with positive results. Sessions were co-led by a peer and “expert” guest speakers from our training institution. Participants completed questionnaires pre and post-program, and feedback evaluations after each session. Questionnaires included the Perceived Stress Scale (PSS), Five Facet Mindfulness Questionnaire (FFMQ), Connor Davidson Resiliency Scale (CDRS-10), and modified Maslach Burnout Inventory (MBI), as well as demographics and open response questions. The primary aim was feasibility (enrollment, completion, and compliance rates), and the secondary aim was acceptability (usefulness of the intervention). Examination of stress, mindfulness, resiliency, and burnout were exploratory. Enrollment and data collection are complete, with 18 of 29 (62%) eligible participants consented. Data analysis is in process.
B-TREUH: A single-arm phase II pilot study of euthyroid hypothyroxinemia in metastatic breast carcinoma.
Authors: Trehan Shruti , Cheng Suzan S. , Hercbergs Aleck
Published: May 2020

TPS1115

Background: It is estimated that there are approximately 155,000 people living with metastatic breast cancer in the US. Studies exploring the connection between hypothyroidism or hyperthyroidism and breast cancer have yielded varying results with up to 33% prevalence of thyroid disease in these patients. L-thyroxine (T4) is the most commonly prescribed agent in the US to manage hypothyroidism. However, there are data suggesting that T4 is a pro-oncogenic agent with proposed mechanisms such as stimulation of mitogenesis, angiogenesis, resistance to apoptosis. In addition, T4 May counter anti-PDL-1 and radiation effects. Triiodothyronine (T3), which is deiodinated form of T4 and also commercially available, is felt to be less oncogenic and less mitogenic. Therefore, exogenous supplementation of T3 would decrease the T4 levels creating the desired state of EUTHYROID HYPOTHYROXINEMIA. The study hypothesizes that replacing L-thyroxine (T4) with Triiodothyronine (T3) in hypothyroid patients with metastatic breast carcinoma, while they simultaneously continue to receive standard systemic therapy, with titrating T3 dose to achieve a state of Euthyroid Hypothyroxinemia would result in improved disease outcomes. Methods: Eligible participants are adults with metastatic breast carcinoma with estimated life expectancy of > 3months, hypothyroidism, and with normal TSH on L-thyroxine (T4). Following consent, participants will discontinue L-thyroixne (T4) and initiate Triiodothyronine (T3) dose based on current T4 dose after an appropriate washout period. Drug titration will be in accordance with thyroid function testing to maintain levels of free T4 at < 50% normal range. The treatment period will continue for 9 months with periodic assessment of disease status, quality of life (FACT-B) and laboratory measures. The primary endpoint is the progression free survival at 12 months while the secondary endpoints are prevalence of hypothyroidism in the cohort, overall survival, quality of life, and duration of time to achieve the Euthyroid Hypothyroxinemia state. Given many uncertainties to calculate power precisely, the sample size is estimated to be approximately 30 patients. Clinical trial information: NCT03787303 .
A phase II/III randomized, blinded study of tozuleristide for fluorescence imaging detection during neurosurgical resection of pediatric primary central nervous system (CNS) tumors: PNOC012 (Pacific Pediatric Neuro-oncology Consortium).
Authors: Leary Sarah , Blatt Jason E. , Cohen Alan R. , Cohen Kenneth J. , Cole Bonnie , Governale Lance , Gupta Nalin , Hauptman Jason S. , Jackson Eric M. , Kebriaei Meysam A. , Kline Cassie , Kobets Andrew , Lee Amy , Miller Dennis Michael , Mueller Sabine , Ojemann Jeff , Prados Michael , Rahman Maryam , Wright Jason N. , Bendel Anne Elizabeth ,   BB-006/PNOC012 Study Group
Published: May 2020

TPS2575

Background: Tozuleristide (also known as BLZ-100 or Tumor Paint) is a fluorescent imaging drug designed to specifically label and accumulate in tumor tissue, thus enabling more precise surgical tumor resection intraoperatively. Tozuleristide achieves tumor targeting through the peptide portion of the molecule, a modified chlorotoxin peptide, and its imaging properties from a coupled near-infrared fluorescent dye, an indocyanine green. Tozuleristide has been studied in 4 Phase 1 studies, including a trial in pediatric brain cancer subjects. No tozuleristide SAEs or dose limiting toxicity were observed in the 97 subjects treated in the Phase 1 program at doses up to 30 mg in adults or 17.3 mg/m2 in pediatrics (Hansen S et al, WMIC 2018, P196). Eighty percent of pediatric subjects receiving tozuleristide had tumors considered fluorescence positive, including high and low grade glioma, ependymoma, and medulloblastoma. Methods: This study randomizes subjects in a 1:10 ratio to standard of care or tozuleristide arms. The primary efficacy objectives and endpoints are based on equivocal regions of tissue encountered in surgery. Prior to fluorescence assessment, the surgeon assesses the suspected nature of the tissue (more likely tumor/less likely tumor). Tissue specimens of equivocal regions are collected for blinded central pathology assessment. Sensitivity and specificity of the surgeon’s designation, fluorescence assessment, and ratios of surgeon to fluorescence assessments comprise the primary efficacy analyses. Tozuleristide is given as an IV bolus dose of 15 mg/m2 to pediatric subjects 1 to 36 hours prior to surgery. Subjects must have a MRI documented lesion consistent with a CNS tumor for which resection is planned. Measures of safety include adverse events, laboratory measures of hematology, liver and kidney function and changes in vital signs and ECGs. Pharmacokinetic blood samples are collected up to 3 hr post dose. Fluorescence imaging is assessed during surgery using an investigational “Canvas System” imaging device attached to a surgical microscope. Collected pathology specimens will also be subjected to further genetic, molecular and pathology studies, including fluorescence assessment of frozen tissue sections. SAEs and patient reported outcomes are collected for 3 months. The SMC for the study last reviewed the data for this study in July 2019 and recommended the trial continue as planned. Clinical trial information: NCT03579602 .
GBM AGILE: A global, phase II/III adaptive platform trial to evaluate multiple regimens in newly diagnosed and recurrent glioblastoma.
Authors: Buxton Meredith Becker , Alexander Brian Michael , Berry Donald A. , Cavenee Webster K. , Colman Howard , De Groot John Frederick , Ellingson Benjamin M. , Gordon Gary B. , Khasraw Mustafa , Lassman Andrew B. , Li Wenbin , Lim Michael , Mellinghoff Ingo K. , Perry James R. , Sulman Erik P. , Tanner Kirk , Weller Michael , Wen Patrick Y. , Yung W. K. Alfred , Cloughesy Timothy Francis ,   GBM AGILE Investigators
Published: May 2020

TPS2579

Background: Glioblastoma (GBM) is an aggressive brain tumor with few effective therapies and is invariably fatal. Developing new therapies for patients with GBM requires focused interaction between industry, academia, nonprofits, patient advocacy, and health authorities, and novel approaches to clinical trials. Industry is wary of developing drugs for GBM due to the high failure rate and high cost of drug development. GBM Adaptive Global Innovative Learning Environment (GBM AGILE) Trial was designed by over 130 global key opinion leaders in consultation with health authorities to provide an optimal mechanism for phase II/III development in GBM. The Sponsor of GBM AGILE is the Global Coalition for Adaptive Research (GCAR), a non-profit organization. GCAR’s mission is to speed the discovery and development of treatments for patients with rare and deadly diseases by serving as sponsor of innovative trials. Methods: GBM AGILE is an international, seamless phase II/III platform trial designed to evaluate multiple therapies in newly diagnosed and recurrent GBM. Its goals are to identify effective therapies for GBM and match effective therapies with patient subtypes, with data generated to support regulatory filing for new drug applications. Bayesian response adaptive randomization is used within subtypes of the disease to assign participants to investigational arms based on their performance. The primary endpoint is overall survival. The trial is being conducted under a master Investigational New Drug Application/Clinical Trial Agreement and Master Protocol, allowing multiple drugs/drug combinations from different pharmaceutical companies to be evaluated simultaneously and/or over time. The plan is to add experimental therapies as new information is identified and remove therapies as they complete their individual evaluation against a common control. GBM AGILE received IND approval from the FDA in April 2019, enrolling its first patient in June 2019. Site activation is ongoing in the US, with approximately 40 US planned. The trial received CTA approval from Health Canada in January 2020. Expansion to Europe, China, and Australia is also underway. Clinical trial information: NCT03970447 .
Phase I trial of drug resistant immunotherapy: A first-in-class combination of MGMT-modified γδ t cells and temozolomide chemotherapy in newly diagnosed glioblastoma multiforme.
Authors: Lamb Lawrence S. , Gibbs Shirley , Pillay Thriumaine , Beelen Melissa , Ho William , Nabors Louis B.
Published: May 2020

TPS3150

Background: Temozolomide (TMZ) transiently upregulates GBM-specific stress-induced NKG2D ligands that are targeted by innate immune effector cells. Leveraging this effect is problematic, however, due to the lymphodepleting effects of TMZ.Genetic modification of ex vivo expanded and activated with an MGMT-expressing lentivector allows simultaneous chemotherapy and γδ T cell therapy that targets the tumor when NKG2DL are maximally expressed. We have termed this Drug Resistant Immunotherapy (DRI). Patient-derived xenograft mouse models of both primary and recurrent GBM treated with DRI have shown a significant survival advantage that were otherwise impervious to either cell therapy or TMZ. These preclinical findings and associated safety data provide the rationale to initiate a Phase I trial of DRI in primary GBM. Methods: This first in human study will evaluate the safety and optimal dosing frequency of the DRI with TMZ (NCT04165941).Eligibility criteria include the following: GBM eligible for resection, ≥18y, adequate organ and marrow function, and KPS≥70. Six to 12patients with newly diagnosed GBM are being enrolled in a 3 + 3 design into 1 of 2 fixed dose levels (DL) of DRI. Following tumor resection and immediately prior to induction chemo/radiotherapy, an apheresis product is collected and γδ T cells expanded in Zoledronic Acid (Novartis) and rhIL-12 (Miltenyi) and transduced with a P140K-MGMT lentivector (Miltenyi Lentigen, Gaithersburg, MD), harvested, and cryopreserved. At initiation of maintenance phase TMZ therapy, patients receive 150mg/m2 intravenous TMZ concurrently with intracranial injection of 1 x 107 γδ T cells (DL1) delivered through a Rickham reservoir previously inserted into the tumor cavity at resection. The patient then receives 4 daily doses of oral TMZ followed by 24d rest. Treatment cycles escalate from 1 to 3 (DL2) DRI doses following a safety observation period and absence of dose limiting toxicity. Maintenance TMZ treatment will continue for 6 cycles. Safety evaluations consist of routine laboratory analyses, clinical measurements (physical exams, vital signs), neurological function and evidence DRI γδ T cell related toxicity. Peripheral blood will be obtained for comprehensive immuno-phenotyping and T cell function analysis. Clinical benefit of DRI will be characterized by evaluating responses (CR, PR, SD and PD) and determining progression-free, median, and overall survival. As of February 2020, enrollment into DL 1 is ongoing. Clinical trial information: NCT04165941 .
A phase Ib study of nivolumab in patients with autoimmune disorders and advanced malignancies (AIM-NIVO).
Authors: Ileana Dumbrava Ecaterina Elena , Suarez-Almazor Maria E. , Painter Jeane , Johanns Tanner , Dougan Michael L. , Cappelli Laura , Bingham Clifton O. , Wang Yinghong , Gupta Sarthak , Warner Blake M , Rahma Osama E. , Naidoo Jarushka , Ott Patrick Alexander , Hafler David A , Kluger Harriet M. , Khosroshahi Arezou , Katsumoto Tamiko R , Kummar Shivaani , Sharon Elad , Tawbi Hussein Abdul-Hassan
Published: May 2020

TPS3158

Background: Immune checkpoint inhibitors (ICI) such as anti-PD-1/PD-L1 antibodies have become a pivotal approach to cancer therapy. Nivolumab is an anti-PD1 antibody approved for an increasing number of solid tumors and hematological malignancies. However, patients (pts) with history of autoimmune disorders are excluded from the majority of clinical trials testing ICI. Consequently, the risks of flares and worsening of pre-existing autoimmune disorders in pts with tumor types who otherwise stand to benefit from ICI therapy are largely unknown, posing a challenge for oncologists. We are conducting a phase Ib study to test the hypothesis that nivolumab can be safely administered to pts with varying severity of Dermatomyositis, Systemic Sclerosis, Rheumatoid Arthritis, Systemic Lupus Erythematosus, Inflammatory Bowel Disease, Multiple Sclerosis, Sjögren's Syndrome and Other Autoimmune Disorders (AIM-Nivo). Methods: AIM-Nivo is an open-label, multi-center ongoing phase Ib study with nivolumab 480mg IV every 28 days in pts with autoimmune diseases and advanced malignancies (NCT03816345). The study has autoimmune disease-specific cohorts overseen by a multidisciplinary group of experts. The primary objective is to assess the overall safety and toxicity profile of nivolumab in pts with autoimmune disorders and advanced malignancies. Secondary objectives are to evaluate the antitumor efficacy, the impact of nivolumab on the autoimmune disease severity indices, and to explore potential biomarkers of response, resistance or toxicity. Key overall inclusion criteria include age ≥18 years, histologically confirmed advanced malignancies in which ICI are approved or have shown clinical activity. Key overall exclusion criteria include prior therapy with anti-PD-1/PD-L1 antibodies. Specific eligibility criteria are defined for each disease-specific cohort. For each autoimmune disorder, severity level of the disease as defined by disease-specific severity indices will be assessed, and up to a total of 12 pts will be included in each disease cohort at each severity level. Primary endpoints are dose-limiting toxicities, adverse events (AEs) and serious AEs. Continuous monitoring of toxicity will be conducted. Key secondary endpoints are best objective response, progression free and overall survival and cohort specific tumor tissue, blood and non-tumor tissue-based biomarkers. The AIM-Nivo trial opened in May 2019 and is enrolling pts through the National Cancer Institute Experimental Therapeutics Clinical Trials Network (ETCTN). Clinical trial information: NCT03816345 .