bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II clinical trial of chidamide in combination with toripalimab in patients with advanced soft tissue sarcoma.
Authors: Zhang Xing , Peng Ruiqing , Pan Qiuzhong , Xu Bushu , Hong Dongchun , Que Yi 
Published: June 2023

11566 Background: Chidamide is an oral subtype-selective histone deacetylase inhibitor which is effective on the patients with hematological tumors and reported to enhance the efficacy of checkpoint blockade therapies and regulate the host immune response. Here, we report preliminary results of Chidamide in combination with Toripalimab in soft tissue sarcoma (STS) patients. Methods: An open, single arm, phase II study of Chidamide with Toripalimab in patients with advanced soft tissue sarcoma after failure of standard treatment was conducted. Eligible patients could have any number of prior therapies, excluding HDAC inhibitors and immune checkpoint inhibitors treatment. All patients received Chidamide orally at 30mg twice weekly in combination with intravenous Toripalimab 240mg every 21 days until progression or unaccepted toxicity. The primary endpoint was RECIST1.1 objective response rate (ORR). The secondary endpoint included progression free survival (PFS), overall survival (OS), disease control rate(DCR) and safety. Results: Forty-six patients with advanced soft tissue sarcoma were enrolled. The median age of the patients was 47 years and the median prior lines of therapy were 3. The main subtypes included leiomyosarcoma (30.4%), well/dedifferentiated liposarcoma (30%), myxoid/round cell liposarcoma (7%), undifferentiated sarcoma(9%), and osteosarcoma (7%). Treatment was well tolerated with the most common adverse events mainly in grade Ⅰ and grade Ⅱ, including thrombocytopenia (43.5%), nausea(28.3%), neutropenia(23.9%), fatigue (17.4%) and hypothyroidism(15.2%). Among 46 efficacy-evaluable patients, the overall response rate and disease control rate were 23.9% and 80.4%, respectively. The median time to an initial response was 3 months (range, 2 to 14), and the 3-mon and 6-mon progression-free survival rate were 92.7% and 58.9%, respectively. Conclusions: Chidamide with Toripalimab every 21 days was well tolerated and showed promising efficacy in patients with advanced STS. Clinical trial information: NCT04025931 .
Efficacy of eribulin administered in combination with an immune checkpoint inhibitor (ICI) and anlotinib as salvage treatment for patients (pts) with advanced adult soft tissue sarcoma (STS).
Authors: Guo Xi , Zhou Yuhong , Zhuang Rongyuan , Zhang Chenlu , You Yang , Li Wei , Wang Zhiming 
Published: June 2023

11572 Background: Eribulin combined with a multi-targeted antiangiogenic tyrosine kinase inhibitor has shown efficacy in STS. ICIs have also exhibited improved survival in some STS subtypes. We investigated the efficacy and safety of triple combination therapy with eribulin, an ICI and anlotinib in the treatment of advanced STS in an adult Chinese population. Methods: This study retrospectively analyzed data from patients diagnosed with advanced STS who received combination therapy with eribulin, an ICI and anlotinib at the Department of Oncology, Zhongshan Hospital affiliated to Fudan University. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) by RECIST v1.1, disease control rate (DCR), and treatment-related adverse events (TRAEs) by CTCAE v5.0. Results: Medical records from 32 pts treated between August 15, 2020 and January 31, 2023 were included; the median age was 56 years, 71.8% (23/32) were female, 75.0% (24/32) had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, and 25.0% (8/32) had an ECOG PS of 2. Pts had received a median of 2 (range 0-6) prior regimens and the median follow-up was 4.1 months. Among the patients, 50.0% (16/32) had liposarcomas (including 1 with pleomorphic liposarcoma and 15 with dedifferentiated liposarcoma [DDLPS]), 31.3% (10/32) had leiomyosarcomas (LMS), 3 had undifferentiated pleomorphic sarcoma (UPS), and 1 each had angiosarcoma, rhabdomyosarcoma and desmoplastic small round cell tumor. In a preliminary analysis, 29 pts were evaluable for clinical activity; partial responses (PRs) were achieved in 3 pts (2 DDLPS, 1 UPS), the ORR and DCR were 10.3% (3/29) and 62.1% (18/29) respectively, and the median PFS was 5.7 months (95% CI 2.7-9.8). Of the 15 pts with DDLPS (median 1 prior line of therapy; median follow-up 6.3 months), 13 were evaluable for clinical activity; a PR was achieved by 15.4% (2/13), the DCR was 61.5% (8/13), the median PFS was 9.8 months (95% CI 1.8-28.5) and treatment was ongoing in 46.7% of pts (n = 7). Among the 9 evaluable pts with LMS, 0 achieved a PR, the DCR was 44.4% (4/9), median PFS was 3.9 months and 3 pts were still receiving treatment. In the overall cohort (n = 32), TRAEs of any grade occurred in 56.3% of pts (n = 18), the most common were myelosuppression (28.1%), fatigue (15.6%), fever (12.5%) and rash (12.5%). Grade 3/4 TRAEs occurred in 12.5% of pts, with no grade 5 events. Conclusions: This study demonstrates the potential efficacy of combination therapy with eribulin, an ICI and anlotinib in patients with advanced STS, especially in those with the DDLPS subtype. Our data suggest that this combination has good tolerability and a prospective trial is warranted. Clinical trial information: ChiCTR2100053594.
Reduced symptom burden after implementation of an electronic symptom management program.
Authors: Bian Jessica J , Ahrens Paige , Tramontano Angela , Cronin Christine , Wong Sandra L. , Osarogiagbon Raymond U. , Hazard-Jenkins Hannah W. , Dizon Don S. , Paudel Roshan , Schrag Deborah , Hassett Michael J. 
Published: June 2023

12006 Background: The SIMPRO consortium implemented an electronic patient reported outcomes (ePRO) symptom management program as part of routine clinical care for patients (pts) receiving systemic cancer therapy or surgery across six health systems including rural and community cancer centers. To evaluate impact of the Epic-integrated electronic symptom management (eSyM) program on quality of life, pre- and post-implementation surveys were sent to a subset of gastrointestinal, thoracic, and gynecologic medical oncology (MO) and surgical (Surg) patients at all sites. Methods: A survey assessing symptom burden, health literacy, and self-efficacy was administered to separate groups of MO and Surg pts before (Pre-Implementation) and after (Post-Implementation) eSyM deployment. A waiver of documentation of consent was obtained for participation. Questions were derived from validated instruments including PROMIS, a standardized measurement tool for patient-reported symptoms. Surveys were completed 30-90 days after surgery or start of systemic therapy. PROMIS item responses were scored individually then translated into standardized T-scores with a mean of 50 based on an established reference population. Mean T-scores for PROMIS depression, anxiety, fatigue, and pain interference were calculated. Higher T-score correlated with greater symptom burden. Comparison between groups utilized non-parametric Kruskal-Wallis testing. Results: The number of survey responses were 498 MO Pre-Implementation, 518 MO Post-Implementation, 566 Surg Pre-Implementation, and 507 Surg Post-Implementation. MO pts reported significantly lower PROMIS mean T-scores for depression, anxiety, fatigue, and pain interference after eSyM compared to a similar group of MO pts prior to eSyM. Surg pts reported lower T-scores for depression, anxiety, fatigue, and pain interference after eSyM compared to a similar group of Surg pts prior to eSyM, although reduction in pain interference was not statistically significant. Conclusions: eSyM deployment in MO was associated with a significant reduction in patient reported depression, anxiety, fatigue, and pain interference. Surgical pts after eSyM deployment reported significantly lower rates of depression, anxiety, and fatigue. External validation with PROMIS based surveys demonstrated small but meaningful benefits of ePRO symptom monitoring as part of routine clinical care across six diverse health systems. Clinical trial information: NCT03850912 . [Table: see text]
Fertility post immune checkpoint blockade.
Authors: Ogle Martinique , Harrold Emily , O'Brien Erin , Weiss Jill A. , Yaqubie Amin , Sinopoli Jenna Cohen , Postow Michael A. , Cercek Andrea 
Published: June 2023

12014 Background: Immune checkpoint blockade (ICB) is radically altering the treatment paradigm for a wide range of malignancies. Consequently, the proportion of ICB exposed pts will expand and the impact of ICB on fertility is of increasing importance. We sought to evaluate fertility outcomes post ICB exposure at our institution. Methods: Pts < 45 years old post ≥ 1 cycles of ICB at MSK who consented to the MSK-IMPACT protocol (NCT01775072) were screened for eligibility (n = 537). Pts in receipt of prior cytotoxic chemotherapy or tyrosine kinase, BRAF or MEK inhibitors were excluded. 96 eligible pts were emailed a 28-question survey; 65% were followed up by phone. Results: 50/96 pts responded to the survey, male to female ratio was 27:23. 5 pts were excluded from final analysis due to additional systemic agent use pre-conception. Median age at ICB exposure was 35 (range 19-44). 53% (25/45) of pts received ICB in the metastatic setting. 40% (17/42) of pts received fertility counseling pre-ICB use. There was no statistically significant difference between rates of fertility counseling in metastatic vs non-metastatic settings (p = 0.14). 7 pts (14%) conceived and 2 pts (4%) are currently trying to conceive children post ICB. 4 pts (3 female, 1 male) conceived children with reproductive technology. 3/4 pts used sperm or embryos frozen prior to ICB and IVF leading to successful pregnancies, 2 of which are currently ongoing. One patient froze embryos 6 months after 2 years of PD1 inhibitor (PD1i) monotherapy and embryo implantation led to a currently ongoing pregnancy. Notably this pt developed hypothyroidism with ICB use, controlled with levothyroxine, and has remained euthyroid during pregnancy to date. 3 pts (2 female, 1 male) receiving single agent PD1i in the localized setting conceived naturally at 2 yrs, 9 months and 2 months respectively post ICB. 4/8 pregnancies are currently ongoing without reported immunological complications. 3 deliveries have resulted in 4 children (including 1 set of twins). 1 of these pts had a 1st trimester miscarriage of unclear cause followed by successful pregnancy complicated by gestational diabetes. First pregnancies occurred a median of 1 year post ICB (range 2-24 months). No autoimmune conditions in progeny were reported. Conclusions: Successful conception occurred both naturally and with reproductive assistance technologies post ICB. Most pts did not receive fertility counseling pre-ICB use, possibly reflective of nascent appreciation of complete and durable ICB responses. There were no definite adverse immunological complications reported in pregnancy or progeny of these pts. As ICB indications expand prospective evaluation of ICB impact on fertility in pts desirous of a family is critical and consequently we are integrating longitudinal fertility analysis in neoadjuvant ICB protocols. [Table: see text]
Long-term outcomes of adolescents and young adults with testicular germ cell tumors: A population-based retrospective matched cohort study.
Authors: Ajaj Rand , Lau Cindy , Gupta Sumit , Baxter Nancy N. , Shaikh Furqan , Nathan Paul C. 
Published: June 2023

12016 Background: Testicular germ cell tumor (TGCT) survival exceeds 90%, but survivors of adult TGCT are at risk of developing late effects. Little is known about the risk for late effects in survivors of TGCT in children, adolescents, or young adults (CAYA). Methods: We identified all CAYA aged 11-21 years at TGCT diagnosis in Ontario, Canada, between 1992-2021. Those with complete treatment records were matched 1:5 by birth date and postal code at diagnosis to individuals from the general population (controls). Controls’ index date was defined as the diagnosis date of their survivor match. Participants were linked to health administrative databases to identify second malignant neoplasms (SMN); cardiovascular disease (CVD: congestive heart failure [CHF], myocardial infarction, coronary artery disease, pericardial disease, valvular abnormalities, arrhythmia, stroke, hypertension); renal disease (dialysis, kidney transplant); and hearing loss (physician-diagnosed hearing loss, hearing aid use). Cumulative incidences were compared between survivors and controls, and between chemotherapy and surgery treated survivors using Gray’s test. Cox proportional hazard models compared the risk of late effects between survivors and controls. Results: 521 TGCT survivors (296 chemotherapy treated, 225 treated with surgery only) were matched to 2605 controls. Median age at diagnosis/index date was 19 years. Survivors’ median follow-up time was 14.8 years (interquartile range: 10.7-21.7). Compared to controls, survivors had higher 15-year incidence and hazard ratio (HR) of all SMN (5.0% vs 0.5%; HR 8.4, p < .0001), non-testicular SMN (2.1% vs 0.5%; HR 3.8, p = 0.0003), dialysis (1.0% vs 0.04%; HR 12.4, p = 0.003), kidney transplant (0.4% vs 0.0%, p = 0.002), hearing loss (7.1% vs 3.1%; HR 1.8, p = 0.005), and hearing aid use (1.0% vs 0.2%; HR 4.1, p = 0.02). Survivors were at substantially increased risk of any CVD (8.2% vs 5.5%; HR 1.4, p < 0.03), CHF (1.2% vs. 0.2%; HR 5.0, p = 0.006), arrhythmia (1.8% vs 0.5%; HR 3.4, p = 0.002), and stroke (0.8% vs 0.05%; HR 8.7, p = 0.0006) despite no anthracycline exposure. Compared to surgery only treated survivors, chemotherapy treated survivors had higher 15-year incidence of any CVD (13.1% vs 2.0%, p < 0.0001), CHF (2.1% vs 0.0%, p = 0.03), arrhythmia (3.3% vs 0.0%, p = 0.02), stroke (1.4% vs 0.0%, p = 0.02), hypertension (7.4% vs 2.0%, p = 0.009), and hearing loss (10.2% vs 3.0%, p = 0.02). Conclusions: Survivors of TGCT during CAYA are at considerable risk for late effects affecting multiple organ systems. In addition to previously described morbidities like hearing loss, survivors (particularly those who received chemotherapy) are at higher risk of CVD. Despite excellent rates of cure, TGCT survivors diagnosed at a young age require life-long risk-directed follow-up to maximize their long-term health.
Social determinants of health burden among adolescent and young adult cancer patients and impact on overall survival.
Authors: Rodriguez Elizabeth , Tonn Tori , Jafry Midhat , Xiao Qian , Cuglievan Branko , Ahmed Sairah , Livingston J Andrew Andrew , Aune Gregory John , Albritton Karen H. , Flowers Christopher , Roth Michael , Hildebrandt Michelle Ann Theobald 
Published: June 2023

12017 Background: The 5-year survival rates for adolescents and young adults (AYA) with cancer have steadily improved, yet disparities by race/ethnicity persist. The drivers of these disparities remain unclear. Neighborhood socioeconomic deprivation has been linked to adverse health outcomes independent of the effects of individual-level measures of social determinants of health (SDOH). We evaluated the impact of neighborhood SDOH on overall survival (OS) in a diverse AYA cancer patient population treated in a single academic setting. Methods: This study utilized a multi-ethnic cohort of AYA cancer survivors (N=10,261) diagnosed between ages 15-39 seen at MD Anderson Cancer Center between 2000 and 2016. Patient demographics, zip code at presentation, cancer characteristics, and follow-up were obtained from our institutional tumor registry. Zip codes were linked to Area Deprivation Index (ADI) values, a validated neighborhood-level SDOH measure, with higher ADI representing worse SDOH. Results: The cohort included 6,361 (62%) non-Hispanic White, 1,112 (10.8%) non-Hispanic Black, and 2,133 (20.8%) Hispanic AYA cancer patients, with 655 (6.4%) of other ethnicities or missing information. The mean ADI value was significantly higher (p<0.05) for Black (61.7) and Hispanic (65.3) patients, compared to White (51.2) patients. Analysis of ADI by cancer type showed significant differences, mainly driven by the significantly higher ADI in patients with cervical cancer (62.3) than other cancer types. In contrast, AYA patients diagnosed with breast cancer (53.0) and CNS tumors (52.9) resided in neighborhoods with the lowest ADI values. ADI was a significant predictor of OS overall. In multivariable models that included gender, age at diagnosis, cancer diagnosis, and race/ethnicity, risk of death for AYA cancer patients residing in neighborhoods with ADI in the highest quartile was greater than that for patients in the lowest quartile (HR: 1.09, 95% CI: 1.00-1.19, p=0.043). Conclusions: Our results in this large multi-ethnic cohort indicate that non-White AYA patients with cancer more commonly live in neighborhoods associated with higher ADI compared to their White counterparts. Even when treated in the same academic setting, AYA cancer patients with higher ADI experienced worse OS across cancers. Although the magnitude of the effect was moderate, the presence of this effect within a tertiary cancer center with existing barriers to care suggests that ADI is a meaningful risk factor impacting survival. Further analysis is warranted to determine the generalizability of these findings to the patient population more broadly. However, the results provide intriguing evidence for potential interventions aimed at supporting AYA cancer patients from disadvantaged backgrounds.
Predicting therapy-induced cardiomyopathy in long-term survivors of childhood cancer: A report from the St. Jude Lifetime Cohort (SJLIFE) and the Childhood Cancer Survivor Study (CCSS).
Authors: Petrykey Kateryna , Wang Huiqi , Dixon Stephanie B , Im Cindy , Ehrhardt Matthew J. , Mulrooney Daniel A. , Sharafeldin Noha , Wang Xuexia , Jefferies John L. , Burridge Paul , Oeffinger Kevin C. , Gramatges Maria Monica , Bhatia Smita , Robison Leslie L. , Ness Kirsten K. , Hudson Melissa M. , Chow Eric Jessen , Armstrong Gregory T. , Yasui Yutaka , Sapkota Yadav 
Published: June 2023

12018 Background: Cancer-therapy-induced cardiomyopathy (CCM) is the leading noncancer cause of mortality among long-term survivors of childhood cancer, the prevalence of which increases with age. Early identification of survivors at risk provides opportunities for targeted prevention strategies. Here, we developed and validated a clinically applicable CCM prediction model based on survivor characteristics, treatment exposures and inherited genetic variation among long-term survivors of childhood cancer. Methods: Long-term survivors from SJLIFE (training cohort; n = 3,350; median age 34 years, range 8-72 years) and CCSS (validation cohort; n = 7,008; median age 36 years, range 11-64 years) were assessed by the five different general population polygenic risk scores (multiPRS) for dilated cardiomyopathy, hypertrophic cardiomyopathy, heart failure, ejection fraction and left ventricular end systolic volume. Multivariable logistic regression was used to predict 15-year risk of the CCM (defined as CTCAE grade ≥3 cardiomyopathy requiring heart failure medications or heart transplantation or leading to death). Model performance was assessed by the area under the receiver operating characteristic curve (AUC). Results: CCM was clinically identified in 150 (4.5%) SJLIFE and self-reported in 156 (2.1%) CCSS survivors, respectively. AUC of clinical models with attained age, sex, age at primary cancer diagnosis, cumulative anthracycline dose, mean heart radiation dose (heart RT), and genetic ancestry was 0.81 (95% CI, 0.78-0.85) in SJLIFE and 0.78 (95% CI, 0.74-0.81) in CCSS. Inclusion of cardiovascular risk factors (hypertension, dyslipidemia, and diabetes) significantly increased AUC to 0.83 (95% CI, 0.80-0.87; P= 0.011; SJLIFE) and 0.84 (95% CI, 0.80-0.87; P< 0.001; CCSS). The addition of the multiPRS further provided significant but modest increases in AUC in SJLIFE (0.84; 95% CI, 0.81-0.87; P= 0.022) and CCSS (0.85; 95% CI, 0.81-0.88; P= 0.031). In low-risk survivors (exposed to < 100 mg/m2 anthracyclines and < 15 Gray heart RT), we observed a possibly larger magnitude AUC increase after adding multiPRS, 0.73 (95% CI, 0.65-0.82) to 0.76 (95% CI, 0.68-0.83; P= 0.11) in SJLIFE and 0.77 (95% CI, 0.65-0.90) to 0.82 (95% CI, 0.69-0.94; P= 0.073) in CCSS. Conclusions: Inherited polygenic factors contributed significantly to improve CCM prediction over available clinical risk factors and may be of benefit to low-risk survivors for whom routine cardiac surveillance is not currently recommended.
Cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting: Results of a phase II/III, placebo-controlled, randomised trial.
Authors: Mersiades Antony , Kirby Adrienne , Stockler Martin R. , Tognela Annette , Olver Ian N. , Morton Rachael L. , Haber Paul , Walsh Anna , Lee Yvonne , Abdi Ehtesham A. , Della-Fiorentina Stephen , Aghmesheh Morteza , Fox Peter , Briscoe Karen P. , Sanmugarajah Jasotha , Marx Gavin M. , Kichenadasse Ganessan , Wheeler Helen , Simes John , Grimison Peter S. 
Published: June 2023

12019 Background: The aim of this multi-centre, randomised, placebo-controlled, phase II/III trial was to determine the efficacy of adding an oral THC/CBD (tetrahydrocannabinol/cannabidiol) cannabis extract in adults who experience CINV during moderate and highly emetogenic intravenous chemotherapy regimens despite guideline-consistent anti-emetic prophylaxis. The phase II crossover component has been published (Grimison et al, AnnOnc 2020). Here we report the definitive results from the combined phase II/III components with a planned sample size of 250 patients. Methods: For the definitive phase III component, participants were randomised 1:1 to receive, oral THC 2.5mg/CBD 2.5mg (Tilray TN-TC11M) capsules TDS days -1 to 5, or placebo (in addition to guideline-consistent anti-emetics including rescue medications) for cycles A, B and C. Primary endpoint was the difference in gaining a ‘complete response’ (no emesis and no use of rescue medications) during 0-120 hours from chemotherapy for cycle A. Results: Complete response was achieved in 24% and 8% with THC/CBD and placebo, respectively (absolute difference 16%, P-value 0.01). The study closed early due to slow accrual without knowledge of study outcomes, with a total of 147 patients recruited 2016-22 (pilot n=78, definitive n=69). Median age was 56 years (range 25 to 80), 78% were females, 39% reported historic cannabis use, 65% were treated with curative intent. Most common regimens were doxorubicin/cyclophosphamide (AC, 31%), and fluorouracil/oxaliplatin (FOLFOX, 17%), 97% received corticosteroid & 5-HT3 antagonist, 80% received NK-1 antagonist, 10% received olanzapine. Efficacy and safety are shown in the table. No SAEs were attributed to THC/CBD. Conclusions: Oral THC/CBD was associated with a significant increase in the proportion of patients achieving a complete response in chemotherapy-induced nausea and vomiting and was well tolerated, representing an effective new treatment in the management of this condition. Future analyses will report quality of life and cost-effectiveness. Funding from NSW Government Dept of Health. Drug supply by Tilray. Clinical trial information: ACTRN12616001036404 . [Table: see text]