bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of nirogacestat in participants with poor prognostic factors for desmoid tumors: Analyses from the randomized phase 3 DeFi study.
Authors: Vincenzi Bruno , Bui Nam , Dileo Palma , Federman Noah , Riedel Richard F. , Van Tine Brian Andrew , Amoruccio Vincent , Lim Allison , Oton Ana B. , Kasper Bernd 
Published: June 2024

11556 Background: Desmoid tumors (DT) are rare, locally aggressive, soft-tissue tumors with a highly unpredictable natural course and substantial patient burden, including pain and functional limitations. Prognosis of DT is potentially dependent on multiple factors, including tumor location, size, patient’s age, mutational status, and presence of pain. Nirogacestat (niro), a targeted gamma secretase inhibitor, is the only treatment approved in the US for adults with progressing DT. In the phase 3 DeFi study, niro demonstrated significant and clinically meaningful improvement vs placebo (pbo) in the primary and key secondary endpoints of progression-free survival (PFS: HR, 0.29 [95% CI: 0.15-0.55]; P<.001), objective response rate (ORR: 41% vs 8%; P<.001), and patient-reported outcomes (pain, DT-specific symptom burden, physical and role functioning, and overall quality of life; P≤0.01, all). The objective of this analysis was to determine the effect of niro in patient subgroups that have been associated with poor prognosis (larger tumor size, younger age, CTNNB1 mutation types, and pain). Methods: DeFi (NCT03785964) was a global, multicenter, double-blind study to determine the efficacy, safety, and tolerability of niro in adults with progressing DT. Patients were randomized 1:1 to niro 150 mg (n=70) or pbo (n=72), taken twice-daily in 28-day cycles. Post hoc analyses of PFS and ORR were conducted in individuals stratified by patient- and tumor-related prognostic factors. Results: PFS and ORR improvement favored niro vs pbo regardless of the patient subgroup, including: baseline tumor size (≤10 cm, >10 cm); age (≤30 y, >30 y); CTNNB1 mutation type (S45F, T41A); and baseline pain (uncontrolled, controlled) (Table). Across the subgroups analyzed, PFS hazard ratio ranged from 0.18 to 0.39, with values <1 favoring niro over pbo. ORR risk difference (niro – pbo) ranged from 18.1% to 56.0%, with values >0 favoring niro. Conclusions: Niro demonstrated consistent improvement in PFS and ORR vs pbo in patients with characteristics implicated as poor prognostic factors for DT—including larger tumor size, younger age, CTNNB1 mutation types, and pain. These results indicate that niro can provide substantial benefit across the subgroups analyzed. Clinical trial information: NCT03785964 . [Table: see text]
Active surveillance in patients with extra-abdominal desmoid-type fibromatosis: A combined analysis of three prospective observational studies.
Authors: Colombo Chiara , Hakkesteegt Stefanie , Le Cesne Axel , Barretta Francesco , Blay Jean-Yves , Grunhagen Dirk J. , Penel Nicolas , Lam Laurent , Fiore Marco , Palassini Elena , Grignani Giovanni , Tolomeo Francesco , Collini Paola , Merlini Alessandra , Perrone Federica , Stacchiotti Silvia , Verhoef Cornelis , Bonvalot Sylvie , Gronchi Alessandro 
Published: June 2024

11573 Background: Three observational studies on active surveillance (AS) in patients with extra-abdominal desmoid-type fibromatosis (DTF) provided prospective evidence supporting AS as frontline approach. Identification of prognostic factors for failure of AS will help determine the appropriate treatment strategy. The aim of this study was to confirm previous findings and investigate the prognostic impact of clinical and molecular variables on a larger series. Methods: Data available on January 31st 2024 from 3 prospective observational studies in Italy, the Netherlands and France in which DTF patients were followed for ≥3 years during an initial AS approach were merged. Patients ≥18 years, with primary extra-abdominal sporadic DTF (abdominal wall, extremity, head & neck, trunk) and with CTNNB1 mutation (T41A, S45F, S45P, WT, “other”) available were eligible for the analyses. The primary study endpoint was treatment-free survival (TFS). Secondary endpoints included incidence of RECIST progression, spontaneous RECIST regression and regression post-RECIST progression. Results: Two hundred and eighty-two patients (n= 282) with median follow up of 53 months (IQ, 39-63) were included. Three-year and five-year TFS and crude cumulative incidences (CCI) of RECIST progression, RECIST regression and regression post-RECIST progression were 69% (64-75%) and 66% (61-73), 34% (95% CI 28-40) and 35% (30-41), 26% (95% CI 21-32) and 34% (29-41), and 35% (95% CI 26-47) and 40% (30-52), respectively. Larger initial tumour size (P=0.031), CTNNB1 mutation (S45F and “other” mutation P=0.049), and head/neck and extremity tumour locations (P=0.032) were associated with worse TFS at multivariable analysis (Table 1). Consistently smaller size and abdominal wall were associated with higher probability of initial spontaneous RECIST regression and a specular trend for mutation was also seen (Table). Conclusions: This study confirms that spontaneous regression occurs in a significant proportion of patients and two third are treatment free at 5 years. Initial size, CTNNB1 mutation and location should be factored in the initial decision-making process. [Table: see text]
Seven year update on SOC-1702: A phase 2 study using trabectedin (T) in combination with ipilimumab (I), nivolumab (N) and trabectedin (T) in previously untreated patients with advanced soft tissue sarcoma.
Authors: Gordon Erlinda Maria , Chawla Sant P. , Omelchenko Nadezhda , Jeffrey Samantha , Agarwal Anmol Dia , Kumar Vaishali , Chawla Neal Shiv , Chua Victoria , Quon Doris V. , Moradkhani Ania , Federman Noah 
Published: June 2024

11577 Background: Advanced soft tissue sarcoma is most often associated with a fatal outcome. This report is an update on the results of the SOC-1702 Phase 2 study for previously untreated STS. Methods: Objectives, Primary: Evaluate best response rate by RECIST v1.1; Secondary: Assess progression-free survival (PFS) at 6 months and overall survival. Patients and Methods: Eligible patients for this Phase 2 study are males or females ≥ 18 years of age with locally advanced unresectable or metastatic soft tissue sarcoma, previously untreated, with measurable disease by RECIST v1.1. Treatment protocol: (I) 1 mg/kg i.v. q 12 wks, (N) 3 mg/kg i.v. q 2 wks, (T) 1.2 mg/m2 CIV q 3 wks. Results: Efficacy: Ninety-one patients were evaluated for efficacy. These subjects completed at least two treatment cycles and had at least one follow-up CT scan. The best responses were 9CR, 14PR, 54SD and 14PD with 25% ORR, 85% DCR. PFS rate at 6 months was 56%; Median PFS was 7.4 (95% CI: 5.6-9.2) months; Median OS was 32.0 (95% CI: 19.8-44.2) months. The best responders (CR and PR) were patients with LMS, UPS, LPS, synovial sarcoma, myxofibrosarcoma, endometrial stromal sarcoma, clear cell sarcoma, DSRCT, and chondrosarcoma. Notably, out of the 91 patients who participated in the study between 2017 and 2022, 23 (25%) patients are still alive as of January 1, 2024, the data cut-off date. Safety: Grade 3/4 TRAEs related to Trabectedin include both hematologic and non-hematologic toxicities: fatigue, nausea, vomiting, fever, exhaustion, dehydration, asthenia, cellulitis of port, anemia, neutropenia, thrombocytopenia, transaminitis, elevated CK. There were no hematologic toxicities related to Nivolumab or Ipilimumab. Grade 3/4 TRAEs include decreased TSH, increased T4, increased TSH, transaminitis, hyponatremia, dehydration, pruritus, and psoriasis. Conclusions: Taken together we have confirmed that (1) Trabectedin in combination with Ipilimumab and Nivolumab is a safe and effective regimen for previously untreated advanced STS, and (2) Randomized studies are needed to confirm whether this regimen is superior to standard first line therapy for advanced soft tissue sarcoma. Clinical trial information: NCT03138161 .
A signal-finding study of nivolumab and relatlimab in patients with advanced chordoma.
Authors: Burkenroad Aaron , Singh Arun S. , Chmielowski Bartosz , Brackert Sandra , Federman Noah , Hagopian Anahis , Glaspy John A , Kendal Joseph , Wessel Lauren E , Hornicek Francis J. , Bernthal Nicholas M. 
Published: June 2024

11578 Background: Chordomas are derived from notochordal remnants and are typically treated with surgery and radiation therapy. For advanced chordomas, there are no approved systemic therapies. Preclinical evidence and anecdotal reports have indicated that the immune system is active in chordomas and that there may be a role for immunomodulation in treating this disease. Methods: This study is a single-arm, signal-finding trial in patients with advanced chordoma treated with the anti PD-1 antibody nivolumab (480 mg Q4 weeks up to 2 years) and the anti-LAG3 antibody relatlimab (160 mg Q4 weeks up to 2 years). The primary objective of this study was to assess the safety of nivolumab and relatlimab in subjects with progressive metastatic or locally advanced/unresectable chordoma. Secondary objectives were to ascertain the median progression free survival (PFS), response rate (RR), and the 4- and 6-month PFS by RECIST 1.1. Results: Out of a planned enrollment of 20 patients, 10 patients (8 Male, 2 Female) were consented and treated on trial. Enrolled patients had the following sites of involvement: 5 clival/c-spine, 4 sacral, and 1 thoracic. Nine had conventional subtype chordoma and 1 had chondroid subtype. Eight of the 10 patients had previous surgery, 6 had previous radiation therapy and 5 had 1-2 lines of prior systemic therapy, including one who received pembrolizumab. Pretreatment biopsies were obtained from 9 out of 10 patients and blood has been collected on all patients. Nine patients were evaluable for study outcomes. A total of 64 AEs (Grades 1-4) have been noted to date, with 6 events being classified as grade 3-4: nausea, facial pain, headache, and pulmonary embolism. Five serious adverse events (SAEs) were noted in patients on treatment: headache (2), asthma (1), myocarditis (1), and sepsis (1). The median PFS of the 9 evaluable patients was 21.4 weeks. At 4 months, 7 out of 9 patients were progression free (77.7%). At 6 months, 4 out of 9 patients remained progression free (44.4%) and had continued progression-free survival at 1 year. One out of 9 (9.1%) patients had a PR via RECIST 1.1. One patient discontinued treatment due to an adverse event (grade 1 myocarditis). Conclusions: This signal-finding study indicated that some patients with advanced chordomas can receive benefit with relatlimab in combination with nivolumab. The combination was well-tolerated and no new safety signals were found in this rare patient population. Correlative studies are ongoing. The study was closed for slow accrual. Clinical trial information: NCT03623854 .
Factors associated with sexual function and sexual satisfaction in young women with breast cancer.
Authors: Ferrigno Guajardo Ana , Fonseca Alan , Miaja Melina , Cruz-Ramos Marlid , Vaca-Cartagena Bryan , Mesa-Chavez Fernanda , Platas Alejandra , Rodriguez Ana Laura , Cabrera-Galeana Paula Anel , Mohar Alejandro , Villarreal-Garza Cynthia 
Published: June 2024

12062 Background: Young women with breast cancer (YWBC) are vulnerable to sexual dysfunction and dissatisfaction due to age-specific psychosocial concerns and treatment side effects. This study aimed to identify factors associated with sexual health in a prospective cohort of YWBC. Methods: Patients aged ≤40 yrs with non-metastatic BC from 3 referral centers completed emotional health, quality of life (QoL), and sexual health assessments at baseline, 6 mos, 1 yr, 2-3 yrs, and 4-5 yrs post-diagnosis. Sexual activity was defined as having had intercourse in the 4 wks preceding each assessment. Female sexual dysfunction (FSD) was defined as a total score <26.55 in the Female Sexual Function Index (FSFI), while hypoactive sexual desire disorder (HSDD) was defined as a score <5 in the desire subscale. Sexual enjoyment was classified with the Sexual Satisfaction Index (SSI), with <110 indicating dissatisfaction. Results: A total of 474 patients with a median age of 36 yrs were included, of which most were married/in a domestic partnership (65%), unemployed (61%), and had an educational level <high school (51%). Most had stage II (49%) or III (39%) disease. The most common molecular subtype was HR+/HER2- (53%), followed by HR-/HER- (26%) and HR+/HER2+ (14%). The prevalence of relevant outcomes at each assessment are shown in the Table. Factors associated with being sexually inactive were low educational level (χ2=7.7), being single (χ2=112.6), having children (χ2=8.12), and higher treatment side effects burden ( p=0.002). Factors associated with worse sexual function were being single (χ2=13.8), amenorrhea (χ2=40.8), HADS-D ≥8 (χ2=11.7), and HADS-A ≥8 (χ2=13.9). Factors associated with lower sexual satisfaction were low educational level (χ2=10.3), being single (χ2=15.5), having undergone bilateral oophorectomy (χ2=5.74), amenorrhea (χ2=8.48), HADS-D ≥8 (χ2=14.98,), and HADS-A ≥8 (χ2=13.91). Additionally, both FSFI and SSI scores directly correlated with QoL (QLQ SumScore) and body image (QLQ-BRBI), and inversely correlated with systemic therapy side effects (QLQ-BRST) ( p<0.001). When analyzing sexual health outcomes according to type of treatment (total vs partial mastectomy, chemotherapy vs no, hormone therapy vs no, anti-HER2 agent vs no), no significant differences were found. Conclusions: Sexual dysfunction and dissatisfaction are highly prevalent in YWBC the first 5 yrs post-diagnosis. As poor sexual health correlates with inferior QoL, patients at an increased risk might benefit from early targeted interventions. [Table: see text]
Trends and racial disparities in palliative care utilization among patients with prostate cancer: A ten-year retrospective study.
Authors: Ozogbo Stanley , Olafimihan Ayobami Gbenga , Jackson Inimfon , Nwachukwu Chiamaka Elsie , Olatunji Gbolahan , Kokori Emmanuel , Aderinto Nicholas , Nzeako Tochukwu , Kim James J. 
Published: June 2024

12068 Background: Due to improvements in cancer therapies and treatment strategies, survivorship among patients with prostate cancer continues to increase, thus necessitating the utilization of palliative care services for symptom management. We examined the prevalence, trends and predictors of palliative care utilization among hospitalized prostate cancer patients in the US. Methods: A retrospective longitudinal study using the Nationwide Inpatient Sample (NIS) database (2010-2019) was conducted. Using join point regression and multivariable logistic regression, trends and factors associated with palliative care receipt were assessed. Results: The overall prevalence of palliative care utilization in the cohort of over 2 million admissions with prostate cancer, was 5.3%. Over the decade, there was a significant increase in palliative care consultations from 2,970 to 7,509 per 100,000 prostate cancer hospitalizations (p-trend <0.001) with an average annual percentage change of 7.7% over the study period. Individuals ≥70 years with prostate cancer had higher odds (aOR): 1.06; 95% CI: 1.01-1.12) of receiving palliative care relative to those < 70 years. Compared to non-Hispanic whites, non-Hispanic blacks were less likely to receive palliative care services (aOR: 0.93; 95% CI: 0.88-0.98). Patients on Medicaid (aOR: 1.51; 95% CI: 1.38-1.65), private insurance (aOR: 1.3; 95% CI: 1.23-1.38) and other insurance types (aOR: 2.2; 95% CI: 1.85-2.55) had higher odds of palliative care utilization when compared to those on Medicare. Prostate cancer patients discharged to facilities or with home health care were more likely (aOR: 6.4; 95% CI: 6.03-6.8) to receive palliative care. Other factors associated with palliative care receipt were non-elective admissions, admission to urban, large and teaching facilities. Furthermore, longer length of hospital stays (≥5 days vs <5 days) was associated with higher utilization of palliative care (aOR: 1.08; 95% CI: 1.05-1.13). Conclusions: Though the trends in palliative care utilization have improved over the years, it remains suboptimal. Additionally, black patients were less likely to receive palliative care. Further studies are needed to explain these disparities and generate interventions to narrow the identified gaps. Addressing the highlighted sociodemographic and hospital-level disparities will ensure optimal utilization of palliative care in this patient population.[Table: see text]
Comparative analysis of efficacy and safety profiles between conventional pegfilgrastim and its biosimilar agents in patients receiving cytotoxic chemotherapy: A systemic review and meta-analysis.
Authors: Nasir Saad , Ali Insia , Naviwala Mohammad Saad Salim , Alidina Zayan , Idrees Hiba , Moosajee Munira 
Published: June 2024

12115 Background: While pegfilgrastim forms the cornerstone in chemotherapy-induced neutropenia prophylaxis, its newer biosimilar agents show potential as compelling options. However, despite head-to-head randomized clinical trials (RCTs) demonstrating comparable efficacy between these biosimilar agents of pegfilgrastim and the conventional pegfilgrastim, a lack of evidence exists to suggest definite clinical benefit. This could be attributed to the low statistical power in the clinical trials. Our systemic review and meta-analysis aim to pool the available evidence and provide a comprehensive understanding of the landscape in the prevention of chemotherapy-induced neutropenia. Methods: A literature search was conducted on online databases including, MEDLINE (PubMed), Embase, SCOPUS, and the Cochrane CENTRAL from their inception to October 2023 to identify phase II or III RCTs comparing the efficacy and safety profiles of the conventional pegfilgrastim and its biosimilar agents. Included studies reported at least one key outcome: the duration of severe neutropenia (DSN) in days after the first cycle of chemotherapy (primary outcome), incidence of febrile neutropenia (FN), and bone pain. Pooled risk ratios (RR) and weighted mean difference (WMD) with 95% confidence interval (CI) were calculated using a random-effects model. Heterogeneity was assessed using I2 statistics. Results: We identified 10 RCTs involving 2237 patients. Our analysis showed a statistically significant and favorable outcome for biosimilar agents in reducing DSN (WMD -0.08 days, 95% CI, -0.15, -0.01, P=0.03, I2=0%). No significant differences were observed in the incidence of FN (RR: 0.98, 95% CI, 0.62, 1.53, I2=0%) or bone pain (RR: 0.98, 95% CI, 0.82, 1.17, I2=0%). In the subgroup analysis based on the subtype of biosimilar agents, eflapegrastim had a statistically significant impact in decreasing DSN compared to the conventional pegfilgrastim (WMD -0.13 days, 95% CI -0.24, -0.03, P=0.01, I2=0%). Conclusions: Growing evidence supports cost-effective biosimilars of pegfilgrastim as comparable in efficacy and safety. Eflapegrastim emerges as a promising alternative, demonstrating a clinically meaningful benefit over the conventional pegfilgrastim.
Frequency of certain germline polymorphisms among ethnicities and adverse drug reaction risk associated with colorectal cancer therapies.
Authors: Jennissen Cathryn , Walker Jason , Elnashar Ghada , England Julie , Hawe Annmarie , Jhun Ellie H. , Tam Victor , Twist Greyson , Kasi Pashtoon Murtaza , Kelley James Michael 
Published: June 2024

12119 Background: Chemotherapy regimens used to treat colorectal cancer (CRC) often include a combination of a fluoropyrimidine (i.e., fluorouracil or capecitabine), folinic acid, irinotecan, and/or oxaliplatin as first-line therapy in metastatic disease. Adverse drug reactions (ADRs) related to these regimens, such as neutropenia, severe diarrhea, and mucositis, can be severe or even life-threatening. Fluoropyrimidine (FP) and irinotecan-related toxicities in CRC are associated with certain germline polymorphisms in DPYD (*2A, *13, HapB3, and c.2846A>T) and UGT1A1 (*28 allele), respectively. Clinically actionable recommendations are available per the FDA and the Clinical Pharmacogenetics Implementation Consortium (CPIC) for DPYD poor metabolizers (PMs) and intermediate metabolizers (IMs) due to increased risk for FP-induced ADRs. The FDA also provides dosing guidance for UGT1A1PMs in an effort to minimize irinotecan-induced toxicities. The objective of this research was to observe the frequency of DPYDvariants (*2A, *13, HapB3, c.2846A>T, c.557A>G), UGT1A1 variants (*6, *28), and associated phenotypes in various racial and ethnic groups. Methods: A retrospective analysis of 8,640 samples genotyped for DPYD and UGT1A1 was conducted (OneOme, Minneapolis, MN). Phenotype and carrier frequencies were analyzed and stratified by self-reported ethnicity and race. Results: DPYD variants with reduced or no function were observed in 6% of all samples tested where 6% of patients having clinically actionable IM or PM status. UGT1A1 carrier frequency was 56% with 12% of patients with clinically actionable PM status. Conclusions: A significant proportion of patients carry DPYD and/or UGT1A1 variants that result in decreased metabolism of FPs and irinotecan, respectively. In this large sample size, a 6% DPYD risk variant carrier frequency is significantly more than an estimated 2%, as previously reported. The FDA and CPIC provide clinically actionable recommendations for these commonly used colorectal and other gastrointestinal cancer therapies in an effort to avoid severe and even life-threatening toxicities that may be potentiated by these germline variations. [Table: see text]
Clinical Decision Support as a Prevention Tool for Medication Errors in the Operating Room: A Retrospective Cross-Sectional Study
Authors: Amici Lynda D. , van Pelt Maria , Mylott Laura , Langlieb Marin , Nanji Karen C. 
Published: June 2024

BACKGROUND:
Medication errors in the operating room have high potential for patient harm. While electronic clinical decision support (CDS) software has been effective in preventing medication errors in many nonoperating room patient care areas, it is not yet widely used in operating rooms. The purpose of this study was to determine the percentage of self-reported intraoperative medication errors that could be prevented by CDS algorithms.

METHODS:
In this retrospective cross-sectional study, we obtained safety reports involving medication errors documented by anesthesia clinicians between August 2020 and August 2022 at a 1046-bed tertiary care academic medical center. Reviewers classified each medication error by its stage in the medication use process, error type, presence of an adverse medication event, and its associated severity and preventability by CDS. Informational gaps were corroborated by retrospective chart review and disagreements between reviewers were resolved by consensus. The primary outcome was the percentage of errors that were preventable by CDS. Secondary outcomes were preventability by CDS stratified by medication error type and severity.

RESULTS:
We received 127 safety reports involving 80 medication errors, and 76/80 (95%) of the errors were classified as preventable by CDS. Certain error types were more likely to be preventable by CDS than others (P < .001). The most likely error types to be preventable by CDS were wrong medication (N = 36, 100% rated as preventable), wrong dose (N = 30, 100% rated as preventable), and documentation errors (N = 3, 100% rated as preventable). The least likely error type to be preventable by CDS was inadvertent bolus (N = 3, none rated as preventable).

CONCLUSIONS:
Ninety-five percent of self-reported medication errors in the operating room were classified as preventable by CDS. Future research should include a randomized controlled trial to assess medication error rates and types with and without the use of CDS.