bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with utilization of palliative care among hospitalized patients with cholangiocarcinoma.
Authors: Ibodeng Gogo-Ogute , Jackson Inimfon , Guarin Geneva , Thanikachalam Kannan
Published: June 2023

e24159

Background: Cholangiocarcinoma has a rising incidence and a low 5-year survival rate. Patients with this malignancy have a very high symptom burden, however, there are only a few studies reported on the prevalence of palliative care utilization in this population. This study examines the prevalence, sociodemographic, hospital-level, and patient-related factors associated with the utilization of palliative care among hospitalized patients with cholangiocarcinoma in the United States. Methods: Data from the National Inpatient Sample, 2016–2020, were used to conduct retrospective cohort analyses. Descriptive analyses were performed to evaluate the prevalence of palliative care consultations among hospitalized patients with a diagnosis of cholangiocarcinoma. Multivariable logistic regression models were used to examine the factors associated with the receipt of palliative care in this population. Results: Approximately 17.9% of our cohort received palliative care during their hospital stay. Cholangiocarcinoma patients aged 65 years and older were more likely to receive palliative care (AOR: 1.19; 95% CI: 1.06–1.32) compared to those less than 65 years. Female patients had 10% higher odds (95% CI: 1.02–1.18) of palliative care utilization relative to their male counterparts. Compared to patients on Medicare, those with Medicaid (AOR: 1.50; 95% CI: 1.29–1.75), private (AOR: 1.27; 95% CI: 1.13–1.42) or other insurance types (AOR: 2.31; 95% CI: 1.95–2.75) were more likely to receive palliative care during their hospital stay. While patients who had elective admissions were less likely (AOR: 0.45; 95% CI: 0.40–0.51) to utilize palliative care relative to those admitted non-electively, those admitted to urban teaching hospitals had 25% higher odds (AOR: 1.29; 95% CI: 1.06–1.57) of palliative care utilization when compared to patients admitted to rural hospitals. Additionally, hospitalized patients with a diagnosis of intrahepatic cholangiocarcinoma had 1.39 times higher odds (95% CI: 1.25–1.55) of receiving palliative care when compared to patients diagnosed with extrahepatic cholangiocarcinoma. Other factors associated with palliative care utilization were hospital region, Charlson comorbidity index and patient disposition. Conclusions: Palliative care consultations among hospitalized patients diagnosed with cholangiocarcinoma remain suboptimal. Our study highlights some of the sociodemographic and hospital-level barriers to the utilization of palliative care services which should guide healthcare providers on areas to improve upon with the goal of improving access to palliative care among hospitalized patients with cholangiocarcinoma.
Platelet decline rate as the indication of using recombinant human thrombopoietin to prevent chemotherapy induced thrombocytopenia: A prospective, randomized, controlled study.
Authors: Wang Zhongliang , Ye Ting , Fan Li , Zhang Jieying , Cao Rubo , Liu Yanshen , Peng Ling , Chen Jing
Published: June 2023

e24171

Background: Doxorubicin combined with ifosfamide is the common regimen for patients with sarcoma, which will induce severe thrombocytopenia. Sarcoma patients especially those with rapid platelet count decline after receiving this regimen could not avoid severe thrombocytopenia, even Recombinant Human Thrombopoietin(rhTPO) was used when the platelet count decreased to 75,000/μL according to current guidelines. The present study aimed to test the efficiency and safety of using rhTPO to prevent severe thrombocytopenia when rapid platelet count decline occurred. Methods: Our previous data showed those patients with rapid platelet count decline more than 40% within 3 days after administration of doxorubicin combined with ifosfamide were more likely to develop severe thrombocytopenia. In this prospective study, 53 patients with this characteristic were randomly assigned to prevention group (starting rhTPO immediately after enrollment) or treatment group (starting rhTPO when platelet count was less than 75,000/μL after chemotherapy). rhTPO was administrated with 300IU/kg·d until the platelet count increased to 100,000/μL or by 50,000/μL. Incidence and duration of grade 3 to 4 thrombocytopenia, proportion of platelet transfusion and adverse reactions were collected and analyzed. Results: The incidence of grade 3 to 4 thrombocytopenia in the prevention group and the treatment group was 63% and 81% respectively (p = 0.224), however the incidence of grade 4 thrombocytopenia in the former was significantly lower than that in the latter(22% versus 50% , p = 0.047).The duration of grade 3 to 4 thrombocytopenia in the prevention group had a declining trend compared with the treatment group( 2.6±2.8d versus 3.7±3.3d, p = 0.198). There was no difference in the proportion of platelet transfusion between the two groups. No rhTPO related toxicities of grade 3 to 4 were observed in both groups. Conclusions: For sarcoma patients treated with doxorubicin combined with ifosfamide, rapid platelet count decline more than 40% within 3 days after chemotherapy can be used as an indicator for the prophylactic administration of rhTPO, which can significantly reduce the probability of grade 4 thrombocytopenia without increasing toxicity. Clinical trial information: ChiCTR1900022667 .
Effects of the coronavirus disease 2019 pandemic on anxiety and spirituality in patients with cancer undergoing chemotherapy: A cross-sectional study.
Authors: Barbosa Oliveira Francisca Fernanda , Sant'Ana Rosane Oliveira , Matos Carlos Anna Clara Aragão , Crispim André Alves , Coelho Lívia Moreira Caetano , Nóbrega Malta Cássia Emanuella , Borges Maria Marcela Fontes , Souza Thuany Pinto Rocha de , Silva-Fernandes Isabelle Joyce de Lima , Picanço-Albuquerque Clarissa Gondim , Silva Lúcio Flávio Gonzaga , Silva Paulo Goberlanio de Barros
Published: June 2023

e24200

Background: The objective of this study was to evaluate anxiety and spirituality levels in oncology patients during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This short-term cross-sectional study applied a previously validated General Anxiety Disorder-7 (GAD7) scale and spirituality inventory to 230 patients undergoing antineoplastic chemotherapy during the second wave of COVID-19 in Brazil. The means ± SD of the scales were calculated and correlated (Spearman's rho). After categorization, chi-square and multinomial regression models were used to identify risk factors (p < 0.05). Results: The levels of anxiety (6.16±5.11) and spirituality (17.22±2.66) were moderately and inversely correlated (p = 0.001, r = -0.212). Women (p = 0.025), fatigue (p = 0.048), and insomnia (p = 0.001) were associated with an increased incidence of anxiety; however, spirituality was associated with a reduced incidence of fatigue (p = 0.032). Death of family or friends due to COVID-19 increased the risk of high levels of anxiety (p < 0.05), while in multivariate analysis, insomnia (p = 0.030) and sleep difficulty (p = 0.031) were also directly associated with anxiety and spirituality reduced the interruption of chemotherapy during the COVID-19 pandemic (p = 0.036). Conclusions: Fear of the COVID-19 pandemic altered the psychoemotional environment of patients undergoing chemotherapy, resulting in increased levels of anxiety. However, spirituality was an important coping strategy in patients undergoing cancer treatment.
Oncology literacy: Educational book for children, families and health professionals.
Authors: Mozzilli Simone Lehwess , Andrade Verônica , Oliveira Milena , Salvetti Marina
Published: June 2023

e24208

Background: With the progress of technology, not only the range of treatments and procedures increases, but also the amount of information and the complexity of the language. Appropriate materials are needed especially when stakeholders have different specificities, but need to speak the same language to understand each other and facilitate engagement in treatment. The aim of this study was to evaluate Beabook, an educational book designed for children with cancer, their family members and health professionals. Methods: The educational book, which has more than 150 terms from the oncology environment and is in more than 200 hospitals and institutions in Brazil, was scored using SAM - Suitability Assessment of Materials, a grading scale to evaluate suitability of health information materials based on categories: content, literacy demand, graphics, layout and typography, learning stimulation and motivation, and cultural appropriateness. Results: The book was analyzed by 61 participants, including children (n = 12) undergoing cancer treatment, remission, palliative care and cured, validating with a score of 26 (maximum scale score - 100%), family members (n = 20): mothers, fathers, siblings, uncles, with a score of 25.6 (98.4%) and health professionals (n = 29): doctors, nurses, psychologists, nutritionists, physiotherapists among others, with score of 25.4 (97.6%), resulting in a final score of 25.6 (98.6%), which represents material above expectations, fully adequate. Conclusions: An educational book suitable for different groups with different perspectives is of great importance in an environment where information is often omitted with the intention of protecting children, ludic communication is confused with fanciful stories and professionals do not have support materials to learn to communicate with patients and families. Studies prove that a unified, standardized and adequate language between stakeholders increases engagement and empowerment, being important mainly in the health area, where helping in the diagnosis and treatment does not imply only in the provision of clinical resources but in the guidance and sharing of information that demystify and build new representations.
Impact of breast cancer on employment in Mexico.
Authors: Villarreal-Garza Cynthia , Gonzalez-Sanchez David G. , Ramirez Arantxa , Vazquez Juarez Daniela , Platas Alejandra , Platas Ana Laura
Published: June 2023

e24219

Background: Women constitute 40% of the workforce in Mexico and are essential contributors to the household and national income. Understanding how BC impacts an individual’s work-life and how the workplace supports patients’ journeys is important to understand the economic burden of this disease. This study focuses on the changes in the employment status of Mexican BC patients after their initial treatment. Methods: An online survey was created and distributed throughout Médicos Investigadores en la Lucha Contra el Cáncer, a BC NGO, social media networks from July to November 2022. Patients with BC who had completed initial treatment and lived in Mexico were invited to participate. The survey consists of multiple-choice questions and the opportunity to explain certain responses. Results were analyzed and visualized using Excel and RAWGraphs. Results: A total of 73 participants completed the survey. The average age (range) of participants was 46 years old (26-66) and 50.7% reported living as a couple. 84% of patients had completed high school or higher education. Most participants had stage 2 (34%) or stage 3 disease (33%). Table 1 describes the employment status of the other 73 participants before, during, and after initiating treatment. 53% considered having the support of their colleagues and employer during their initial treatment. The rest considered that their work environment was indifferent (21%), offered no support (14%), or decided not to disclose their diagnosis (12%). Additionally, some patients commented about workplace discrimination because of their disease: “Customers wouldn’t purchase clothes because my lack of a breast disgusted them” (after a radical mastectomy) and “I was forced to quit because “it was better for me” and they were afraid I would infect them.” Financial necessity (45%) and a return to normalcy (33%) were the main motivators to return to work, and 14% did not wish to continue working at the time of the survey. Conclusions: After their initial treatment, the majority of patients in this study underwent changes in employment status or stop working altogether. A considerable portion of the participants did not feel supported by their workplace and some even faced discrimination due to their disease. Future studies need to be conducted to understand the physical and psychological aspects, and the employer and societal factors that limit cancer survivors’ successful return to work in Mexico. Advocacy and reform must be undertaken to decrease workplace discrimination and balance work-life and breast cancer care. [Table: see text]
Interpersonal concerns of young adult surgical oncology patients with advanced cancer diagnoses: A mixed methods study.
Authors: Sun Beatrice J. , Pang Emily , Lee Byrne
Published: June 2023

e24225

Background: Incidence of cancer in young adults (YA) is increasing. YA patients with advanced cancer are more likely than elderly counterparts to undergo elective or palliative surgeries. A diagnosis of advanced malignancy poses unique social and emotional burdens on YA. This study aims to understand the experiences of YA cancer patients in managing interpersonal relationships and social expectations. Methods: This mixed-methods study consisted of cross-sectional patient quality of life (QOL) surveys (Functional Assessment of Cancer Therapy: General [FACT-G]), caregiver QOL surveys (Caregiver QOL – Cancer [CQOLC]), and semi-structured qualitative interviews with patients. Participants were YA ages 18-45 years with advanced-stage cancers, recruited from surgical oncology clinic at a tertiary academic institution. Interviews were transcribed and analyzed by two independent reviewers to describe themes (italicized) on social and interpersonal impacts of patients’ cancer diagnosis. Results: Interviews and patient surveys were conducted with 18 YA patients. Median time since cancer diagnosis was 15 months, 44% of patients had metastatic disease at diagnosis, and 89% of patients had previously undergone both chemotherapy and surgery for cancer treatment. 56% of patients identified their spouse or significant other as the person they were closest to, and 28% were closest to a parent or sibling. 56% of patients had children of their own who lived in the household. Median FACT-G scores were 23/28 for social/family well-being (IQR: 18-25) and 13/28 for emotional well-being (IQR: 8-17). Caregiver surveys were completed for 12 of 18 patients, revealing that most developed a closer relationship with their loved one (67%) and felt informed about their disease (92%). Qualitative interview analysis revealed themes of: information-sharing about cancer, where patients shared concerns of withholding prognostic information to give loved ones hope; impacted relationships with friends and colleagues, as patients struggled with who to disclose their cancer diagnosis to; social/physical perceptions by others, as patients worried about changes in their physical appearance (e.g. weight loss) as a result of cancer; financial concerns as a result of treatment and its future impact on the patient’s loved ones. Conclusions: This mixed methods study highlights the interpersonal concerns of YA with advanced cancers. At a phase where identity formation, social perceptions, and personal relationships may be threatened by cancer, unique psychosocial and emotional challenges arise. Programmatic changes are needed to provide appropriate support, resources, and empathetic care to this distinct population of cancer patients.
Characterization of pre-malignant lesions in patients with pediatric neurofibromatosis type 1 using a novel whole-body magnetic resonance imaging technique.
Authors: Baca Nicole M. , Majlessipour Fataneh (Fae) , Xie Yibin , Posadas Edwin Melencio
Published: June 2023

TPS10637

Background: Neurofibromatosis Type 1 (NF-1) patients can develop benign tumors, plexiform neuromas (PN), that may transform into malignant peripheral nerve sheath tumors (MPNST)(Tucker, et al. 2009). MPNST are rare; but in NF1, the lifetime incidence is 8-13% and MPSTs present at younger ages(Miettinen, et al. 2017). MPNST are aggressive tumors requiring full resection for best outcomes (Mautner, et al. 2008). Emerging data suggests whole-body MRI (WB-MRI) can identify NF patients with higher PN tumor burden and maybe at risk of developing MPNST. We have created a rapid, motion-robust quantitative WB-MRI technique that is likely suitable for pediatric patients. High-resolution multiparametric tissue mapping, including T1, T2, and ADC (apparent diffusion coefficient), are acquired concurrently in a single scan, as shown in prior studies (Christodoulou, et al. 2018, Ma, et al. 2020, Nguyen, et al. 2016, Wang, et al. 2020). This project will evaluate the feasibility and reproducibility of novel WB-MRI for the characterization of pre-malignant lesions in NF-1 patients. Methods: Trial Design: Pilot study of novel WB-MRI technique in pediatric NF-1 patients with a goal of 15 patients between the ages of 5-17 years. Trial MRI scans are performed at baseline, 1 month, and then 12 months (+/-3 months). A clinical 3T MR scanner (Siemens MAGNETOM Vida) performs a head-to-knee WB-MRI in 70 minutes. Signal-to-noise ratio (SNR) and imaging quality scores will be evaluated. The lesion volume and mean T1/T2/ADC are measured for each lesion on the corresponding quantitative maps based on manual ROI’s (regions of interest). To assess scan-rescan reproducibility, image quality metrics (SNR and quality score), lesion identification, and lesion characteristics (T1, T2, and ADC) will be compared between the baseline and the 1-month scan using a Bland-Altman analysis and Schuirman’s equivalence. The coefficient of variation (CV = 100 [SD/mean] %) values for each of the quantitative values will be calculated. To evaluate for lesion characterization, changes in the mean in each MRI quantitative metrics (T1, T2, and ADC) will be measured for each lesion on the baseline and 12-month visit. Spaghetti plots will be used to visualize the change over time, and the difference in mean will be tested using an appropriate parametric or nonparametric test depending on the results of tests on normality and homoscedasticity. Intervention: WB-MRI at baseline, 1 month, and 12 months (+/-3 months) Eligibility: 5 to 17 years old not requiring sedation; Clinically or molecularly diagnosed NF-1 including mosaic/segmental subjects; Not Eligible: allergy to animal dander, animal-instigated asthma, pregnant, breastfeeding, or have intrauterine device; Current Enrollment (February 2023): 5 subjects (One unable to finish a non-sedated MRI). Clinical trial information: NCT04763109 .
UCLA B-13: A phase 1b trial evaluating the safety of ribociclib, tucatinib, and trastuzumab in patients with metastatic, HER2+ breast cancer and a multicenter, randomized, open-label, phase 2 study of preoperative treatment with ribociclib, trastuzumab, tucatinib, with or without fulvestrant versus docetaxel, carboplatin, trastuzumab, and pertuzumab in HR+/HR-, HER2+ breast cancer.
Authors: McAndrew Nicholas Patrick , Hurvitz Sara A. , Tetef Merry L. , Kivork Christine , Ikenouye Larissa , Slamon Dennis J.
Published: June 2023

TPS1116

Background: Overexpression of the HER2 protein is an important prognostic and predictive biomarker in about 20% of breast cancers, and while trastuzumab-based regimens are still considered standard of care in the early and metastatic settings, these regimens require chemotherapy co-administration. Pre-clinical mouse models suggest that a tucatinib/CDK 4/6 inhibitor combination regimen may be equally effective as standard regimens. Thus, finding more effective/tolerable therapies for this disease remains an area of unmet need. This randomized, open label, phase II clinical trial will explore the safety and efficacy of two novel, chemotherapy free combination drug regimens, given neoadjuvantly, in patients with anatomic stage I-III, HER2+ breast cancer. Methods: Phase 1b dose escalation trial: To establish the safety profile of the combination of ribociclib and tucatinib, an initial dose-finding phase 1b trial will be performed in patients with metastatic HER2+ breast cancer before moving into the larger phase 2 trial. 3-6 patients will be assigned sequentially to groups of increasing doses of ribociclib (200mg-600 mg) with fixed doses of tucatinib (300mg) and trastuzumab (SOC dosing) for a total of four 28-day cycles. The recommended phase 2 dose will be established when 6 patients have been treated at the highest dose level cohort. As of January 2023, 1 participant has been enrolled in dose level 1. Phase 2 neoadjuvant trial: Following MTD determination and approval from regulatory boards and funding partners, a total of 100 patients will be enrolled in the phase 2 portion of the study. Enrollment will be stratified by hormone receptor status. Patients will be randomized 1:1 (25 in each group) to receive six cycles of one of the following regimens: ribociclib/trastuzumab/tucatinib/+/- fulvestrant (28 day cycles) or docetaxel/carboplatin/trastuzumab/pertuzumab (SOC, 21 day cycles), preceded by one run-in cycle of trastuzumab/pertuzumab. To assess for changes in predictive molecular biomarkers, biopsies pre-and-post cycle 1 will be planned in all arms. Early imaging response assessments in the experimental arms will be planned after 2 cycles. Other endpoints include safety, changes in Ki67 expression, RCBi, biomarker analysis, and health-related quality of life. Clinical trial information: NCT05319873 .
The ARETHA study: A phase 2 randomized control trial of eribulin with evexomostat (SDX-7320) or placebo for patients with metastatic triple-negative breast cancer (TNBC) and metabolic dysfunction.
Authors: Shen Sherry , Solomon Verna , Williams Dominiq , Robson Mark E. , Norton Larry , Traina Tiffany A. , Iyengar Neil M.
Published: June 2023

TPS1131

Background: The prognosis for advanced/metastatic TNBC remains poor and novel therapeutic strategies are urgently needed. Insulin resistance and obesity contribute to TNBC progression and are independent predictors of worse survival. Methionine aminopeptidase 2 (MetAP2/p67) is overexpressed in many tumor types including breast. MetAP2 inhibitors exhibit broad anti-tumor activity and attenuate the effects of metabolic dysfunction on tumor growth. Evexomostat (SDX-7320) is a second-generation MetAP2 inhibitor that improved insulin sensitivity, reduced fat mass, and normalized adipokine levels in preclinical models of obesity and reduced tumor growth in TNBC preclinical models. In phase 1 trials, evexomostat monotherapy partially restored insulin sensitivity, reduced adipokines, and showed anti-metastatic effects in patients with advanced solid tumors. The goal of this phase 2 study is to test whether evexomostat prevents worsening of insulin resistance and augments tumor response in patients with metastatic TNBC and metabolic dysfunction in combination with eribulin chemotherapy, a standard of care treatment option after prior anthracycline and taxane exposure. Methods: This is a single-center phase 2 randomized control trial of evexomostat, a MetAP2 inhibitor, and eribulin chemotherapy. Key eligibility criteria include metastatic TNBC, measurable disease or ≥1 predominantly lytic bone lesion, baseline hemoglobin A1c >5.5% and/or BMI ≥30 kg/m2, and ≤2 prior lines of therapy in the advanced/metastatic setting. Patients with uncontrolled or insulin-dependent type II diabetes, or who require combination antihyperglycemic therapy are excluded. During the safety run-in period, 15 patients will be assigned to receive evexomostat 49 mg/m2 Q2 weeks and eribulin 1.4 mg/m2 on days 1 & 8 of a 21-day cycle. Upon safety confirmation, an additional 40 patients will be randomized 2:1 to receive evexomostat or placebo with eribulin. The primary endpoint is metabolic efficacy assessed by change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score. Secondary endpoints include objective response rate, progression-free survival, safety and tolerability, patient-reported outcomes, and changes in metabolic markers and body composition. Historically, HOMA-IR scores double during chemotherapy, and this trial will test whether evexomostat attenuates the expected HOMA-IR rise. This trial will have >90% power to detect a difference between a 1.5-fold change in HOMA-IR in the control arm vs. no change in the evexomostat arm while controlling the Type I error at 5%. As of Feb 2022, 3 patients are enrolled; total accrual of 61 patients is planned with a goal of 55 evaluable patients. Clinical trial information: NCT05570253 .
Comprehensive 0utcomes for After Cancer Health: COACH.
Authors: Lally Robin Mary , Schmidt Rachael , Tlusty Gisele , Jackson Mariah Kay , Arthur Elizabeth , Barr Austin , Flora Laura , Hammer Marilyn J. , Jones Jessica Trevino , Lynch Kelly Debra , Krok-Schoen Jessica L. , Loftis Jennifer , Saligan Leorey , Starkweather Angela , Vazquez Michael , Whisenant Meagan , Wright Alexi A. , Brassil Kelly Jean
Published: June 2023

TPS12141

Background: The landscape for cancer survivors continues to evolve as individuals live longer following primary therapy. For some, treatment is complete; for others, active surveillance or maintenance therapy may be indicated. Individual survivorship needs are diverse, influenced by tumor and treatment type, as well as social determinants of health. Digital interventions may support survivors in achieving personalized health goals throughout survivorship. The Comprehensive Outcomes for After Cancer Health (COACH) Study (NCT05349227) explores the feasibility of a digital health coaching (DHC) program for individuals enrolled with diverse tumor types and geographic regions. Methods: COACH is a multi-center, randomized, wait-list control trial enrolling 550 individuals ≥18 years old who are within 1-year of completion of primary cancer therapy at enrollment. Up to 100 participants, will be recruited at each of 6 study sites, of which 3 are currently enrolling. Consented individuals are randomized to 6 months of DHC or 6 months of data collection only, then cross-over for follow-up to 12-months. Both groups wear an activity tracker; complete patient reported outcome measures; and provide fecal specimens. The DHC program includes weekly Health Advisor calls and supplemental delivery of evidenced-based content via text, email or mobile platform. Topics fall in health domains of physical, mental/emotional, financial, social, and sexual, and emphasize nutrition, physical activity, sleep, and screening for recurrent or de novo cancer. Feasibility for this study is defined as a retention rate greater than or equal to 70%, and acceptability will be defined as less than or equal to 20% scoring “not at all helpful.” Trends over time will be assessed using linear mixed models using time as a fixed effect, as well as any covariates and interactions of interest. Descriptive statistics will be used to evaluate exploratory endpoints. A cross-cohort end-point related to physical function as measured by the PROMIS Physical Function 10a, will also be evaluated. To date, 72 individuals have enrolled, with Nebraska as the lead site, including 71 women, with a mean age of 61.78 (Range 33-74), from the U.S. Midwest (n = 57) and Northeast (n = 15). 4 identify as African American/Black, 68 as White. 50 have a breast, 13 ovarian, 8 endometrial, 1 gastric diagnosis. Nine have completed the first 6 months of the study. The study is novel in the breadth of data collected and potential to understand variability in patient experiences and provide insights into the feasibility, acceptability, and efficacy of a DHC intervention supporting individuals after primary cancer treatment. Clinical trial information: NCT05349227 .
Empathic communication skills training: Randomized controlled trial to reduce lung cancer stigma in lung cancer care.
Authors: Ostroff Jamie S. , King Jennifer C. , Ciupek Andrew , Nichols Brittney , Malling Charlotte , Rosenthal Lauren , Banerjee Smita C.
Published: June 2023

TPS12152

Background: Stigma is commonly experienced by people diagnosed with lung cancer and is often triggered during clinical encounters with their oncology care provider (OCP), particularly associated with routine assessment of smoking history. Lung cancer stigma is associated with gaps in quality of care as well as poorer psychological and physical health-related outcomes for patients. The overall objective of this multi-site national clinical trial is to test whether an OCP-facing training intervention in empathic communication skills (ECS) reduces stigma and distress and promotes patient engagement. Our prior pilot work has demonstrated that the ECS intervention is both feasible and efficacious to reduce stigma during clinical encounters. Methods: This NCI-funded multi-site national trial employs a cluster randomized design comparing usual care (waitlist control) with ECS training (intervention). With outreach and site recruitment support provided by GO2 for Lung Cancer and the American Cancer Society, community oncology sites (n = 16) nationwide will be randomized 1:1 to each arm. 9-11 OCPs will be recruited per site with 6 unique patients per OCP enrolled (total 54-66 patients/site). Statistical analysis will evaluate the effect of ECS training on primary OCP outcomes (e.g., empathic skill uptake) and secondary patient-reported outcomes (e.g., psychological distress). The 2.5 hour ECS training is delivered live using a videoconference platform. The didactic content covers knowledge and consequences of stigma on patients with lung cancer and in-depth review of specific ECS strategies. Participants then engage in experiential small-group role-play sessions with trained patient actors, where they are given tailored feedback by trained facilitators and their peers. Eligible sites must have at least 15 OCPs and clinic volume of at least 20 new patients with lung cancer per month. Eligible OCPs (physicians, NPs and PAs) must currently be treating and conducting outpatient clinic consultations with at least 1 patient with lung cancer per week. Eligible patients must be receiving treatment for lung cancer, English and/or Spanish speaking, currently or formerly smoking, and have had no more than 5 prior visits with the participating OCP. Currently, this trial is open to accrual and has 5 sites across the nation completing paperwork for activation. Clinical trial information: NCT05456841 .
Mixed-methods clinical trial to evaluate the feasibility of the CURATE.AI optimised digital cognitive rehabilitation therapeutic (COR-Tx) in patients post brain radiotherapy.
Authors: Raczkowska Marlena N. , Remus Alexandria , Vijayakumar Smrithi , Kwek Siong Peng , Lee V Vien , Tadeo Xavier , Ng Grady , Lau Ni Yin , Leong Qiao Ying , Chai Qian Yee , Aliyah Fatin , Blasiak Agata , Chia Wei Tsau David , Asplund Christopher L. , Ho Dean , Vellayappan Balamurugan A.
Published: June 2023

TPS1615

Background: Cognitive decline may be exacerbated, in brain tumour patients, by prior radiotherapy (RT). Traditional interventions to mitigate this typically involve fixed dose or intensity pharmacological and/or cognitive rehabilitation therapies that often elicit sub-optimal or no response, due to the dynamically evolving patient state and low adherence. Personalised digital therapeutics (DTx) may be more effective for this population. Further, gamification has previously shown to induce positive health behavioural change and improve intervention adherence. To this end, we have developed the CURATE.AI COR-Tx platform, a gamified DTx, that combines a previously validated, small-data artificial intelligence-derived dose optimisation technology with digital multitasking cognitive training. This novel DTx dynamically personalises treatment by using the patient’s own longitudinal performance data to generate an evolving digital avatar that guides training intensity throughout the intervention. Herein, we aim to evaluate feasibility, user experience and usability of the DTx platform in brain tumour patients post-RT. Methods: This is a prospective, mixed-methods, interventional, single-arm, decentralised feasibility clinical trial. The primary objective is to evaluate feasibility of the CURATE.AI COR-Tx platform as both a digital intervention (DI) and digital diagnostic (DD) for cognitive function in 15 patients with brain tumour post-RT. The personalised and home-based DI involves completing three 12-min sessions per week for 10 weeks, starting 1 month post-RT. Cognitive function will be assessed via a combined non-digital cognitive evaluation and a DD session at five time points: prior to RT, pre- & post-DI and 16- and 32-weeks post-DI. Feasibility outcomes relating to acceptability, demand, implementation, practicality and limited efficacy testing and additional secondary and exploratory outcomes relating to usability and user experience will be collected by the clinical team and through semi-structured patient interviews and a study team focus group discussion at study completion. We will adopt a mixed-methods approach for data analysis. Feasibility of the CURATE.AI COR-Tx platform will be evaluated through thematic analysis for qualitative outcomes (acceptability and practicality), and descriptive and correlational analysis for quantitative outcomes (demand and implementation). We will adopt the CONSORT traffic light system to decide on future expansion into a large-scale randomised control trial. This trial began in April 2021 and has enrolled 14 of planned 15 patients at the time of submission. Clinical trial information: NCT04848935 .
A first-in-human study of XTX301, a masked, tumor-activated interleukin-12 (IL-12), in patients with advanced solid tumors.
Authors: Knecht John George , Gupta Anurag , Duncan Meghan , Crowe David , Patel Ekta , O'Neil Jennifer , Lee George , Luptakova Katarina , Gutierrez Martin
Published: June 2023

TPS2672

Background: Interleukin-12 (IL-12) is a proinflammatory cytokine that has shown promise as an immunotherapy for cancer. Although it has demonstrated potent antitumor activity in mouse models of cancer, development of IL-12 in the clinical setting has been limited by severe toxicities with systemic administration. XTX301 is a half-life extended, masked and tumor-activated IL-12. XTX301 is designed to be pharmacologically inactive in non-tumor tissue when circulating systemically, and unmasked by matrix metalloproteases (MMPs) preferentially active in the tumor microenvironment (TME). The masking domain is engineered to be removed via cleavage at a protease cleavage site in the XTX301 linker by MMPs. XTX301 is designed to produce a localized anti-tumor immune response while limiting exposure of the active form of XTX301 in non-tumor tissue, and thereby improving the therapeutic index of IL-12. Using a murine analog of XTX301 (mXTX301), tumor growth inhibition was demonstrated in vivo in murine models with a single dose of mXTX301. In mouse tumors, mXTX301 stimulated the infiltration of cytotoxic CD8+ T cells and induced pro-inflammatory gene expression signatures. Preclinical data have demonstrated tumor-selective activity of mXTX301 in mice with limited and reversible peripheral toxicities of XTX301 in non-human primates [Malkova et al., AACR 2023]; these data are supportive of further clinical development. Methods: XTX301-01 trial (NCT05684965) is a first-in human, multicenter, Phase 1, open label study to establish the safety and tolerability of monotherapy XTX301, and to determine a recommended phase 2 dose (RP2D). Additional objectives include assessment of pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity and anti-tumor activity of XTX301. The study will enroll patients with solid tumors, including lymphoma, that have locally advanced or metastatic disease and have failed standard therapy, standard therapy does not confer survival benefit, or standard therapy is not available. Patients in part 1A will receive XTX301 monotherapy every 3 weeks via intravenous infusion in an outpatient setting, using a 3+3 dose escalation design. The starting dose for XTX301 is 5 ug/kg. Part 1B will further examine multiple doses of XTX301 as monotherapy in patients with select advanced solid tumors to further characterize PK, PD and dose response relationships. Part 1B will require mandatory fresh tumor biopsies before and after initiation of study drug administration to fully characterize the PD profile and PK of XTX301 in the tumor. Enrollment to the study is planned to begin in the first quarter of 2023. Clinical trial information: NCT05684965 .
A prospective observational study investigating the impact of immune checkpoint inhibitors for cancer on fertility in males and females of child-bearing age (immuno-fertility).
Authors: Keogh Rachel J , O'Reilly David , Marks Sam Jonathan , Horan Maebh , Elebert Rachel , Glover Louise , Milewski Maciej , Egan Keith , Hennessy Bryan T , Grogan William , Morris Patrick G. , Breathnach Oscar S. , Murphy Adrian Gerard , Wingfield Mary , Crosby David A , Naidoo Jarushka
Published: June 2023

TPS2679

Background: Anti-PD-1/PD-L1/CTLA4 agents have revolutionized the treatment landscape of many cancer types, resulting in durable responses. With recent approvals in the adjuvant setting, the long-term consequences of immune checkpoint inhibitors (ICIs) such as the impact on fertility are of increasing clinical relevance. The impact of ICI therapy on fertility is poorly understood. Based on published data, we hypothesize that patient fertility may be affected by ICIs via several mechanisms, including: endocrine dysfunction, direct impact on gametogenesis, or autoantibody formation. Methods: We designeda prospective, multi-center translational study that aims to identify the effects of ICIs on fertility. We aim to recruit 88 patients over 3-4 years. Participants of child-bearing age as defined by study protocol who are due to start ICIs for any solid tumour malignancy, will be eligible. The primary endpoint of the study is a change in anti-Müllerian hormone level and antral follicle count in females, and a change in sperm concentration, motility, morphology in males measured before and serially during ICI therapy (up to 24 months). Secondary endpoints include analysis of FSH, LH, testosterone levels, the proportion of patients with a persistent change in any one reproductive parameter as assessed at follow-up visits, frequency of oligo/amenorrhoea in females and immunologic changes in seminal fluid in males. Conclusions: ICIs have led to a significant improvement in the long-term survival in selected patients with cancer. This study will elucidate the effects of ICIs on both male and female fertility over time, and provide useful information to guide patients and their care teams regarding long-term effects of ICIs on fertility. Recruitment is ongoing.
TROPION-Lung04: Phase 1b, multicenter study of datopotamab deruxtecan (Dato-DXd) in combination with immunotherapy ± carboplatin in advanced/metastatic non-small cell lung cancer (mNSCLC).
Authors: Borghaei Hossein , Waqar Saiama Naheed , Bruno Debora S. , Kitazono Satoru , Wakuda Kazushige , Spira Alexander I. , Olivares Jairo , Mak Gabriel , Lovick Susan , Goodwin Louise , Papadopoulos Kyriakos P.
Published: June 2023

TPS3158

Background: Datopotamab deruxtecan (Dato-DXd) is a TROP2-directed antibody drug conjugate that has shown encouraging preliminary activity and safety in patients (pts) with lung or breast cancers. The TROPION-Lung04 study was designed to assess the safety, tolerability, and antitumor activity of Dato-DXd in combination with immunotherapy ± carboplatin in pts with advanced or metastatic NSCLC. Methods: TROPION-Lung04 (NCT04612751) is a Phase 1b, multicenter, open-label, 2-part, dose escalation/confirmation and expansion study in ≈232 pts without actionable genomic alterations. In Part 1 (dose escalation/confirmation), pts will be enrolled to 1 of up to 11 cohorts. Details of cohorts 1–4 (Dato-DXd [4 or 6 mg/kg] + durvalumab [1120 mg Q3W] ± up to 4 cycles of carboplatin [AUC 5] Q3W) were previously described (Borghaei H, et al. JTO 2021;16(10):S1098-S1099). Cohorts 5–11 were recently added to evaluate Dato-DXd in combination with bispecific immunotherapies AZD2936 (anti-PD-1/TIGIT) and MEDI5752 (anti-PD-1/CTLA-4) in treatment-naïve pts. Pts in cohorts 5–8 will receive Dato-DXd (4 or 6 mg/kg) + AZD2936 ± carboplatin; pts in cohorts 9–11 will receive Dato-DXd + MEDI5752 ± carboplatin. Cohorts 5 and 6 will recruit pts with PD-L1 tumor proportion score (TPS) ≥50% in Parts 1 and 2A, and PD-L1 TPS 1–49% in Part 2B. Cohorts 7–11 will recruit pts with PD-L1 TPS < 50% only. Dose confirmation in Cohorts 5–11 will be guided by an mTPI-2 design where a minimum of 6 and a maximum of 9 pts will be assessed for dose-limiting toxicities (DLTs) during Cycle 1; if the DLT incidence meets prespecified toxicity criteria, Part 2 dose expansions may be opened. Pts may continue Dato-DXd or immunotherapy treatment until disease progression (per RECIST v1.1) or unacceptable toxicity. Study endpoints are shown in the table. Enrolment across all combination cohorts is ongoing. Clinical trial information: NCT04612751 . [Table: see text]
First-in-human clinical trial design of a first-in-class theranostic approach with a peptide-based radioligand targeting CA IX-expressing tumors.
Authors: Feldman Darren R. , Tran Ben , Emmett Louise , Hofman Michael S , Olivier Pierre , Mahammedi Hakim , Galetic Ivana , Pokorska-Bocci Anna , Bouisset Florilene , Gollmer Kathrin , Pavlyuk Mariya , Tauchmanova Libuse , Herrmann Ken
Published: June 2023

TPS3160

Background: Expression of carbonic anhydrase IX (CA IX), a cell surface glycoprotein, can be induced by a state of hypoxia or by mutation of the Von Hippel-Lindau tumor suppressor gene. CAIX expression in tumors is often associated with progressive disease and overall poor outcomes in various solid cancers. Notably, high CA IX expression has been observed in 83%, 40%, and 29% of clear cell renal cell carcinoma (ccRCC), pancreatic ductal adenocarcinoma (PDAC), and colorectal cancer (CRC) specimens, respectively1. CA IX may therefore represent a valuable therapeutic target. DPI-4452 is a first-in-class cyclic peptide that binds with high affinity to CA IX. Radiolabeling DPI-4452 with gallium-68 ([68Ga]Ga-DPI-4452) or lutetium-177 ([177Lu]Lu-DPI-4452) is an innovative theranostic approach for identifying and treating patients (pts) with CA IX-expressing tumors. Pre-clinical data has shown that [177Lu]Lu-DPI-4452 is taken up by tumors and induces dose-dependent growth inhibition in ccRCC and CRC xenograft mouse models1,2. Methods: We present the design of a Phase I/II study (NCT05706129) of [68Ga]Ga-DPI-4452 and [177Lu]Lu-DPI-4452 in pts with unresectable locally advanced or metastatic ccRCC, CRC or PDAC. The study is comprised of three phases: imaging (Part A), dose-escalation (Part B), and expansion (Part C). In Part A, pts will receive a single intravenous (IV) 185 MBq dose of [68Ga]Ga-DPI-4452. Safety, tolerability, pharmacokinetics (PK), dosimetry and imaging characteristics of [68Ga]Ga-DPI-4452 will be evaluated using positron emission tomography/computed tomography (CT) at four timepoints on Day 1. All pts will be followed for seven days post-injection for safety observations. In Part B, based on [68Ga]Ga-DPI-4452 uptake, pts will receive sequential, escalating doses of IV [177Lu]Lu-DPI-4452 on Day 1 of each 28-day cycle for up to eight cycles. During Cycle 1, each pt will undergo up to four whole-body planar imaging and single photon emission CT/CT analyses for dosimetry over seven days. In Part B, the recommended Phase 2 dose of [177Lu]Lu-DPI-4452 will be determined, guided by a Bayesian Logistic Regression model. Safety, PK, and dosimetry will be assessed to minimize any radiation-induced toxicity and to optimize absorbed radiation dose in the tumor. Upon completion of Part B, Part C will enroll up to three cohorts of pts with CA IX-positive ccRCC, CRC or PDAC to assess preliminary efficacy of [177Lu]Lu-DPI-4452, with a primary endpoint of objective response rate, as measured by RECIST v1.1. References Wiedemann N et al. J Nucl Med 2022;63(Suppl 2):4048. Attinger A et al. Eur J Nucl Med Mol Imaging 2022;49(Suppl 1):S1–S751. Clinical trial information: NCT05706129 .
MOUNTAINEER-03: Phase 3 study of tucatinib, trastuzumab, and modified FOLFOX6 as first line treatment in HER2+ metastatic colorectal cancer.
Authors: Bekaii-Saab Tanios S. , Van Cutsem Eric , Tabernero Josep , Siena Salvatore , Yoshino Takayuki , Nakamura Yoshiaki , Raghav Kanwal Pratap Singh , Cercek Andrea , Heinemann Volker , Adelberg David E. , Ramos Jorge , Yang Shan , Andre Thierry , Strickler John H
Published: June 2023

TPS3631

Background: The current standard of care (SOC) for the treatment of metastatic colorectal cancer (mCRC) is multi-agent chemotherapy, with or without a VEGF or EGFR inhibitor. Human epidermal growth factor receptor-2 (HER2) is a validated clinical target in breast and gastric cancers. HER2 amplification occurs in 3%–5% of patients with mCRC; the rate of HER2 amplification can increase to approximately 10% in patients with RAS/BRAF wild-type mCRC tumors. Tucatinib (TUC)—a highly selective, HER2-directed tyrosine kinase inhibitor—is approved in multiple regions for HER2-positive (HER2+) metastatic breast cancer, approved in the US for HER2+ metastatic colorectal cancer, and under investigation in gastrointestinal cancers. MOUNTAINEER (NCT03043313) evaluated the safety and efficacy of TUC and trastuzumab (Tras) in patients with treatment-refractory RAS wild-type, HER2+ mCRC. Results from the primary endpoint analysis showed clinically meaningful activity, with a confirmed objective response rate (ORR) per blinded independent central review (BICR) of 38.1% (95% confidence interval [CI] 27.7, 49.3) and median duration of response per BICR of 12.4 months (95% CI 8.5, 20.5). Results also demonstrated TUC + Tras was well tolerated, with a low discontinuation rate (5.8%) and no deaths due to adverse events. MOUNTAINEER-03 will further investigate TUC in combination with modified FOLFOX (mFOLFOX) and Tras in patients with RAS wild-type HER2+ mCRC. Methods: MOUNTAINEER-03 (NCT05253651) is a global, open-label, randomized, phase III study for first-line treatment of HER2+ and RAS wild-type mCRC. Approximately 400 patients will be randomized 1:1 to the TUC experimental arm (TUC [300 mg orally twice daily] + Tras + mFOLFOX) or the SOC arm (mFOLFOX alone or in combination with either bevacizumab or cetuximab). HER2 status is determined centrally with tissue-based HER2 immunohistochemistry and in situ hybridization assays. Eligible patients must not have received prior treatment in the metastatic setting but may have received adjuvant treatment if completed > 6 months prior to enrollment. Patients must be ≥18 years old with an Eastern Cooperative Oncology Group Performance Status of ≤1 and RAS wild-type mCRC. Patients with treated stable central nervous system metastases are eligible. Randomization is stratified by primary tumor location (left-sided vs other) and liver metastases (presence/absence). The primary endpoint is progression-free survival per RECIST v1.1 assessed by BICR. Key secondary endpoints are overall survival and confirmed ORR per RECIST v1.1 assessed by BICR. Enrollment is ongoing in North America, Asia, Australia, and Europe. Clinical trial information: NCT05253651 .