bluuebunny/crossref_metadata_2025_split huggingface dataset:
The accuracy of the Psychological Distress Inventory – Revised (PDI-R) in identifying distress in oncological outpatients: A pilot study using a machine learning approach.
Authors: Rossi Alessandro Alberto , Marconi Maria , Mannarini Stefania , De Cicco Luigi , Verusio Claudio 
Published: June 2023

e24222 Background: Ever greater importance is given to psychological distress in oncological settings. Distress could have a severe adverse effect on adherence and compliance to therapies, medical treatments, and quality of life (NCCN, 2015). Moreover, psychological research is progressively increasing in oncological settings and psychological distress has rapidly gained popularity – leading to the development of scales aimed at its evaluation. In this regard, the revised version of the Psychological Distress Inventory – the PDI-R (Rossi et al., 2022) – has demonstrated excellent psychometric properties but its screening properties were limited to self-report questionnaires. Consequently, to fill this gap, this study aimed to evaluate the accuracy of the PDI-R in identifying the levels of distress of oncological outpatients compared to a diagnostic interview – using a machine learning approach. Methods: Oncological outpatients ( n = 603; mean age = 68.38, SD = 9.31; 316 males) were enrolled at the Presidio Ospedaliero of Saronno, ASST Valle Olona, Italy. Patients were tested with the PDI-R which is composed of 8 items that evaluate internal, external, and general distress. In this study, the PDI-R shows good internal consistency: McDonald’s omega = .922. Then, patients were interviewed by a psycho-oncologist who assessed distress levels of each patient. In accordance with the methodological procedures for the application of machine learning algorithms, patients were randomly divided into two different databases. The first database ( n = 400) was used to train the machine learning algorithm and the second one ( n = 203) was used to test the accuracy of its predictions. The k-nearest neighbors ( k-NN) algorithm was applied. Results: According to the clinical interview, the training database (mean age = 67.78, SD = 9.10; 212 males) shows that 76% of patients were without distress (or mild distress) and 24% had moderate or severe distress. Moreover, according to the clinical interview, the testing database (mean age = 69.58, SD = 9.62; 104 males) shows that 71% of patients were without distress (or mild distress) and 29% had moderate or severe distress. Using the 8 items of the PDI-R, the k-NN algorithm, correctly identified 193 subjects (144 true negatives and 49 true positives). At the same time, only 10 subjects (10 false negatives) were incorrectly classified – thereby showing a machine learning-based accuracy of 95%. Conclusions: These findings suggest that the PDI-R is a reliable self-report questionnaire with strong psychometric properties and high accuracy in identifying psychological distress. Its use in research and clinical practice is therefore recommended to increase the quality of both assessment and treatment of psychological distress in patients with oncological difficulties.
Exploring the unmet needs of Mexican women living with metastatic breast cancer: A patient survey.
Authors: Enriquez Luis Fernando , Reyes-Lizaola Sebastian , Vazquez Juarez Daniela , Platas Alejandra , Platas Ana Laura , Villarreal-Garza Cynthia 
Published: June 2023

e24223 Background: Breast cancer is the most prevalent form of cancer among women worldwide and the top cause of cancer-related fatalities. In Mexico, delayed diagnosis and referral contribute to a significant proportion of breast cancer patients being diagnosed with metastatic breast cancer (mBC) or experiencing distant recurrences. Patients with mBC face unique needs and concerns for their illness, which are frequently not attended to or covered. Gaining insight into their diagnostic experiences is crucial for enhancing the standard of care. The aim of this study is to explore the unmet needs of Mexican women living with mBC. Methods: An anonymous and voluntary survey was distributed to women diagnosed with mBC. The instrument employed was drawn from the European "Being There" study and underwent translation into Spanish in accordance with the current best practices for the translation and cultural adaptation of health measurement tools. The survey addressed various subjects including patient’s personal experiences concerning diagnosis and treatment, attitudes of healthcare providers toward cancer services, information available to patients, and patients' views on enhancing future care. Results: A total of 29 responses were received from women ranging in age from 26 - 74 years. Despite generally positive feedback on the care received (42% as excellent/very good, 55% as good/acceptable, and only 3% as bad), these women identified areas for improvement. Regarding their personal experience receiving information about their diagnosis and treatment, 86% reported receiving medical attention that helped them cope with their illness and 80% reported being convinced that the medical team was highly qualified and coordinated. However, only 55% of physicians and 44% of nursing staff displayed interest in the patients' goals and wishes after they received their diagnosis. Regarding the attitudes of healthcare providers in cancer services, 62% of the women believed that they should be more empathetic, 65% would like to see the same doctor/nurse/specialist on every visit, and 69% indicated that they would like them to show more interest in the challenges they face on a day-to-day basis. Table 1 summarizes the information that these women would like to receive about their treatment. Conclusions: In conclusion, this study provides insight into the experiences and unmet needs of women living with mBC in Mexico. While the care received by the women was generally positive, the study highlights the need for improvement in certain areas to address their unmet needs. The findings can be used to enhance the standard of care for women with mBC. [Table: see text]
Evaluation of palbociclib in combination with topotecan and cyclophosphamide in pediatric patients with recurrent or refractory neuroblastoma.
Authors: Laetsch Theodore Willis , Navid Fariba , Weigel Brenda , Fox Elizabeth , Hawkins Douglas S. , Muscal Jodi Ann , Juszczak-Kosela Katarzyna Alicja , Zhang Zhe , Macy Margaret E 
Published: June 2023

TPS10069 Background: Palbociclib is an orally administered, highly selective, reversible, small molecule cyclin-dependent kinases 4/6 (CDK4/6) inhibitor. Inhibition of CDK4/6 reduced growth of neuroblastoma cell lines. The phase 1 portion of the study, conducted and funded by Pfizer in collaboration with the Children's Oncology Group, established the recommended phase 2 dose (RP2D) of palbociclib with topotecan and cyclophosphamide (TOPO/CTX) in children with solid tumors. Per study protocol, if 2 or more patients from the phase 1 study show a confirmed objective response (OR) in a specific tumor type, an open-label, non-randomized tumor-specific cohort (TSC) may be opened. Methods: A neuroblastoma TSC has been opened to evaluate the preliminary antitumor activity of palbociclib with TOPO/CTX in the treatment of patients with recurrent/refractory neuroblastoma using a modified Simon’s 2-stage optimal design. Up to 21 patients will be enrolled and receive palbociclib with TOPO/CTX. The primary endpoint is OR, as assessed by investigator using International Neuroblastoma Response Criteria (INRC). Secondary efficacy endpoints include duration of response, progression-free survival, and overall survival. Key eligibility criteria include: recurrent/refractory neuroblastoma, measurable disease as defined by INRC, aged ≥2 and < 21 years at the time of study entry, adequate blood counts organ function, and performance status. Patients may have received prior TOPO and/or CTX, provided their disease did not progress on this regimen. Prior treatment with a CDK4/6 inhibitor is exclusionary. Patients will receive palbociclib at the RP2D of 75 mg/m2 orally once daily on days 1–14 of each 21-day treatment cycle. CTX (250 mg/m2) followed by TOPO (0.75 mg/m2) will be administered intravenously once daily on days 1–5. Concurrent radiotherapy or surgery for local control will be permitted. Treatment will continue until disease progression, patient and/or legal guardian refusal, unacceptable toxicity , or up to 24 months of treatment, whichever occurs first. Enrollment in the neuroblastoma TSC was initiated in December 2022 ( NCT03709680 ). Clinical trial information: NCT03709680 .
Update for NCI-COG Pediatric MATCH: Active trial cohorts for children, adolescents and young adults with refractory cancers.
Authors: Parsons Donald Williams , Janeway Katherine A. , Laetsch Theodore Willis , Irwin Meredith , Alva Elizabeth , Pratilas Christine A. , Franson Andrea Flynn , Patton David R. , Saguilig Lauren , Piao Jin , Alonzo Todd Allen , Berg Stacey L. , Fox Elizabeth , Hawkins Douglas S. , Mooney Margaret M. , Takebe Naoko , Tricoli James V. , Seibel Nita ,   NCI-COG Pediatric MATCH Team
Published: June 2023

TPS10071 Background: The National Cancer Institute–Children's Oncology Group Pediatric Molecular Analysis for Therapy choice (MATCH) trial seeks to facilitate evaluation of molecular-targeted therapies in biomarker-selected cohorts of childhood and young adult patients with cancer by screening tumors for actionable alterations. The Pediatric MATCH screening protocol and first seven treatment arms were activated in July 2017 for patients treated at COG sites across the United States; six additional treatment arms were activated between 2017 and 2020. In 2022 a major screening protocol amendment discontinued centralized tumor testing at MATCH laboratories and mandated use of molecular profiling reports from outside laboratories to determine treatment arm eligibility. Methods: The trial assigns patients aged 1 to 21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase 2 treatment arms of molecularly-targeted therapies based on the genetic alterations detected in their tumor. Starting in January 2022, a clinical tumor molecular profiling report from a CAP/CLIA-approved laboratory has been required for patients to enroll in the screening protocol. The treating site indicates which molecular alteration in the submitted report is believed to be actionable as well as the open Pediatric MATCH study arm for which the patient is proposed to be eligible. The submitted report is then reviewed by the study Molecular Review Committee to determine if an actionable alteration is present (based upon study-defined levels of preclinical and clinical evidence): if so, the patient is assigned to the relevant MATCH treatment arm. Other treatment arm eligibility requirements are typical of phase 2 pediatric trials including adequate patient performance status and standard washout periods for prior therapy. Each treatment arm follows a one (arms A, D, F, M, N) or two (arm K) stage design with a 20 patient primary cohort and option for histology-specific expansion cohort(s) if at least 3 objective responses are seen in a tumor histology. The primary endpoint is objective response rate; secondary endpoints include safety/tolerability and progression-free survival. Therapy is discontinued if there is evidence of progressive disease or drug related dose-limiting toxicity that requires removal from therapy; therapy may otherwise continue for up to 2 years. As of January 2023, 6 of the 13 Pediatric MATCH treatment arms remain open to enrollment (Table). Clinical trial information: NCT03155620 . [Table: see text]
Phase IIa study of αDC1 vaccines targeting HER2/HER3 combined with pembrolizumab in patients with asymptomatic brain metastasis from triple negative breast cancer or HER2+ breast cancer.
Authors: Gandhi Shipra , Forsyth Peter A. J. , Opyrchal Mateusz , Ahmed Kamran A. , Attwood Kristopher , Levine Ellis Glenn , O'Connor Tracey L. , Early Amy P. , Fenstermaker Robert Alan , Prasad Dheerendra , Takabe Kazuaki , Czerniecki Brian J. , Kalinski Pawel 
Published: June 2023

TPS1112 Background: Brain metastases develop in up to 50% patients (pts) with metastatic triple negative breast cancer (TNBC) and HER2+ BC, constituting an increasing source of morbidity and mortality. HER3, overexpressed in triple negative and HER2+ brain metastatic breast cancer (BMBC), is a resistance factor to HER2-targeted therapies and a driver of CNS metastasis. Disease progression is associated with loss of anti-HER2 and anti-HER3 immunity. Previously, we have demonstrated that glioma-specific peptide-loaded αDC1 which produce CXCL9, CXCL10, CXCL11, CCL5, the chemokines which attract CXCR3- and CCR5- expressing cytotoxic T-lymphocytes (CTLs) and T-helper 1 (Th1) cells, induce clinical responses and long-term disease stabilization in pts with aggressive recurrent primary brain tumors (Okada et al. JCO 2011. PMID: 21149657). We hypothesized that anti-HER2/3-loaded αDC1 in combination with PD1 blockade will result in strong Th1/CTL response against HER2/3 epitopes (Basu A et al. Cancer Immunol Res. 2022 PMID: 34785506), being effective against brain lesions and systemic disease. Methods: This is a phase II single-arm, non-randomized multicenter study (NCT04348747). Eligibility includes pts with triple negative and HER2+ BMBC ≥18 years, ECOG PS ≤1, normal marrow and organ function with asymptomatic untreated brain metastases ≥ 5 mm who will receive αDC1 q3 weeks x 3 along with pembrolizumab every 3 weeks. Thereafter, αDC1 booster doses (if available) would be administered every 3 months until disease progression, intolerable side effects or withdrawal from study, up to 24 months. Baseline and 9-week post-αDC1 peripheral biopsies (non-CNS) are required for six pts. 1 of the planned 21 pts have been enrolled and is undergoing treatment. Primary endpoint is CNS response rate (RR) by RANO-BM criteria. If no CNS response is observed after 12 pts, study will be terminated. If ≥ 1 response observed, then 9 more pts will be enrolled, for a total of 21 pts. If ≥ 3 CR are observed, the proposed therapy will be considered as promising for further evaluation. Secondary endpoints include non-CNS RR per RECIST v1.1, median CNS, non-CNS and overall progression-free survival, overall survival and safety. Exploratory endpoints include changes in intratumoral biomarkers (CTLs, PDL1, chemokines) in pre- and post-treatment peripheral tumor biopsies and immune changes in the blood. Clinical trial information: NCT04348747 .
VERITAC-2: A global, randomized phase 3 study of ARV-471, a proteolysis targeting chimera (PROTAC) estrogen receptor (ER) degrader, vs fulvestrant in ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer.
Authors: Campone Mario , Ma Cynthia X. , De Laurentiis Michelino , Iwata Hiroji , Hurvitz Sara A. , Wander Seth Andrew , Danso Michael A. , Lu Dongrui Ray , Perkins Smith Julia , Liu Yuan , Tran Lana , Anderson Sibyl , Hamilton Erika P. 
Published: June 2023

TPS1122 Background: ARV-471 is an oral PROTAC ER degrader that binds to and degrades wild-type ER and clinically relevant mutants. ARV-471 directly recruits the ubiquitin-proteasome system to degrade ER, whereas selective ER degraders (SERDs) indirectly cause ER degradation. In a first-in-human phase 1/2 study, ARV-471 monotherapy was well tolerated and showed clinical activity in heavily pretreated patients with ER+/HER2- advanced breast cancer. The phase 3 monotherapy dose (200 mg once daily [QD]) was chosen due to comparable efficacy and favorable tolerability relative to 500 mg QD and robust ER degradation in paired tumor biopsies. The randomized phase 3 VERITAC-2 study (NCT05654623) will compare efficacy and safety of ARV-471 vs the SERD fulvestrant in patients with ER+/HER2- advanced breast cancer after prior combination cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy and endocrine therapy (ET). Methods: Eligible patients (aged ≥18 years) have a confirmed diagnosis of ER+/HER2- locoregional recurrent or metastatic breast cancer not amenable to surgical resection or radiation; 1 prior line of combination CDK4/6 inhibitor therapy and ET; ≤1 additional line of ET; most recent ET given for ≥6 months before disease progression; and radiological disease progression during or after the last line of therapy. Prior chemotherapy in the locally advanced or metastatic setting and prior fulvestrant are not permitted. Patients (N~560) are randomized 1:1 to receive 200 mg ARV-471 orally QD continuously or fulvestrant intramuscularly on days 1 and 15 in the first 28-day cycle and on day 1 in subsequent cycles; patients are stratified by ESR1 mutation status and presence of visceral disease. The primary endpoint, progression-free survival, will be assessed by blinded independent central review in the intention-to-treat population and the ESR1 mutation sub-population. Secondary outcome measures include overall survival, antitumor activity (objective response rate, duration of response, and clinical benefit rate), safety, and quality of life assessments. Clinical trial information: NCT05654623 .
CAPTOR-BC: Comprehensive analysis of spatial, temporal and molecular biomarkers predicting response and resistance to first-line treatment with ribociclib + ET in HR+, HER2- advanced breast cancer.
Authors: Fasching Peter A. , Brucker Sara , Huebner Hanna , Thewes Verena , Volmer Lea Louise , Hartkopf Andreas Daniel , Kolberg Hans-Christian , Lex Benno , Aktas Bahriye , Ditsch Nina , Haeberle Lothar , Seitz Katharina , Anetsberger Daniel , Nabieva Naiba , Roos Christian , Belleville Erik , Schneeweiss Andreas , Mueller Volkmar , Janni Wolfgang , Fehm Tanja N. 
Published: June 2023

TPS1124 Background: The combination of an oral CDK4/6 inhibitor with endocrine therapy (ET) has become the standard first-line therapy for women with advanced HR+ HER2- breast cancer. In this context, the broadest clinical trial data are available for ribociclib, a highly selective CDK4/6 inhibitor, with three phase III trials (MONALEESA-2, -3 and -7) consistently showing a significant overall survival benefit compared to ET monotherapy regardless of treatment line, menopausal status or combination partner. However, de novo or acquired resistance to CDK4/6 inhibitors does occur and biomarkers predicting treatment response or providing information on resistance mechanisms are only beginning to be understood. Comprehensive identification and validation of biomarkers before and during ribociclib therapy is needed to better understand mechanisms leading to disease progression, which will be the first step towards developing novel therapies and optimizing treatment sequences. Methods: CAPTOR-BC (NCT054552213) is a single-arm, open-label phase IV study evaluating the combination of ribociclib and ET according to SmPC in the first-line treatment of HR+ HER2- advanced breast cancer to identify and validate molecular and non-molecular biomarkers predictive of drug response and resistance. First patient first visit occurred in October 2022 and at least 1000 patients across more than 75 sites in Germany will be enrolled until October 2025. Progression-free survival (PFS) and overall survival (OS) at 12 months are the co-primary endpoints, quality of life (QoL) and toxicity are secondary endpoints. Exploratively, a comprehensive multi-omics biomarker discovery and validation program is integrated into the study: Besides tumor tissue, liquid biopsies profiling circulating tumor (ct)DNA, ctRNA, whole blood RNA, proteins from serum and plasma, and circulating immune cells will be evaluated before, during and after treatment or upon progression to determine correlations with PFS, OS, QoL and adverse events. Clinical trial information: NCT05452213 .
A phase 1b/2 dose escalation and expansion study of OP-1250 in combination with ribociclib or alpelisib in patients with advanced and/or metastatic estrogen receptor–positive (ER+)/HER2-negative (HER2-) breast cancer.
Authors: Borges Virginia F. , Chan Arlene , Lin Nancy U. , Tonda Margaret Eleanor , Shilkrut Mark , Alemany Carlos A. 
Published: June 2023

TPS1127 Background: Therapies targeting the estrogen receptor (ER) are standard of care in the management of ER+/HER2- metastatic breast cancer (MBC) and when administered concurrently with cyclin-dependent kinase (CDK) inhibitors are the most effective first-line therapy. CDK 4/6 inhibitors plus endocrine therapy improve progression-free survival and, for some agents, overall survival for patients with MBC. However, most patients will acquire resistance, highlighting an unmet need for more effective endocrine options in ER+ disease. OP-1250 is a small molecule oral complete estrogen receptor antagonist (CERAN) and selective estrogen receptor degrader (SERD) that binds the ligand binding domain of ER and completely blocks ER-driven transcriptional activity. OP-1250 potently inactivates both wild-type and mutant forms of ER, the latter of which confers ligand independent activity as a mechanism of resistance to standard of care endocrine therapies. In preclinical studies, OP-1250 in combination with CDK4/6 inhibitors demonstrated synergistic activity in models of both wild-type ER and those with ESR1 (the gene that encodes ER) activating mutations, and in brain metastasis. OP-1250 is orally bioavailable with a favorable pharmacokinetic (PK) profile supportive of once-daily dosing, and a low probability of drug:drug interactions, making it an attractive agent for patients with ER+/HER2- MBC. Methods: The study (NCT05508906) is an open-label, multicenter, 2-part study of OP-1250 in combination with either the CDK4/6 inhibitor ribociclib or the PI3K inhibitor alpelisib for patients with MBC. Eligibility includes adults with evaluable (measurable or non-measurable) ER+/HER2- recurrent, locally advanced or MBC confirmed by histology/cytology, ≤2 prior hormonal regimens (prior CDK4/6 inhibitors allowed) and ≤ 1 prior line of chemotherapy. Patients in the alpelisib arm must have a PIK3CA mutation. A total of 30 patients will be enrolled in each arm. The dose escalation cohorts will evaluate the safety and PK of varied OP-1250 doses (30mg, 60mg, or 120mg) administered orally (PO) every day (QD) in combination with approved dosages of either ribociclib 600 mg PO QD or alpelisib 300 mg PO QD to identify the recommended phase 2 doses (RP2D). The dose expansion cohorts will assess additional safety and PK parameters and further explore the anti-tumor activity of OP-1250 in combination with ribociclib or alpelisib. Tolerability, safety and PK of OP-1250 in combination with ribociclib or alpelisib constitute the primary endpoints. Overall response rate, clinical benefit rate and duration of response are key secondary endpoints. Enrollment at approximately 20 sites in the United States and Australia is ongoing. Clinical trial information: NCT05508906 .