bluuebunny/crossref_metadata_2025_split huggingface dataset:
U.S. FDA analysis of enrollment of Asian patients from India in cancer clinical trials leading to approval from 2010 to 2022.
Authors: Srivastava Geetika , Leong Ruby , Nair Abhilasha , Kanapuru Bindu , Rizvi Fatima , Yang Felice , Lee Jennifer J. , Wedam Suparna B. , Dilawari Asma Ali , Fan Chaohong , Lee Sso , Andrada Frances , Lee Clara , Rivera Donna , Lemery Steven , Gao Jennifer , Kim Tamy , Pazdur Richard 
Published: July 2024

e13779 Background: There are an estimated 4.4 million Indian Americans (Asian Indian), constituting 1.35% of the United States (US) population. Indian Americans enrolled in clinical trials are identified under the broad race category of Asian which includes Asians within the US and outside of US (Ex-US). Although cancer is the leading cause of death for Asians in US, they are under-represented in cancer clinical trials. Enrollment of Asian patients from India (API) in multiregional oncology clinical trials may provide important data regarding intrinsic and extrinsic factors impacting the etiology of cancer as well as response to anti-cancer treatment in Indian Americans. Common cancers reported amongst Asians in US are breast, prostate, colorectal, and lung, and in India are breast, head and neck, cervical and lung. Methods: We analyzed data from ~96,000 patients in 164 cancer therapeutic trials that led to an FDA approval for breast, prostate, colorectal, lung, liver, gastric, head and neck and cervical cancer indications from 2010-2022, and identified country for enrollments for all Asians. Results: Descriptive statistics of Asian patients enrolled within US, Ex-US and from India enrolled in breast, prostate, colorectal, lung, liver, gastric, head and neck, and cervical cancer trials that led to an FDA approval from 2010-2022 are summarized (Table). Enrollment of Asian patients within US was ≤1% (except liver and cervical cancer), from India was ≤2.1% of all Asians enrolled outside of US and ≤0.7% of all enrolled patients. Conclusions: It is difficult to accurately characterize the exact number of Indian Americans enrolled but are likely under-represented in cancer clinical trials leading to FDA approval.Sponsors should collect more granular information regarding enrollment of Asian patients in clinical trials. Enrollment of patients from India is extremely low relative to the population size. Efforts to increase enrollment of Indian Americans as well as patients from India in oncology clinical trials can bolster the evidence that supports FDA drug approval and its applicability to Indian Americans. [Table: see text]
PENTA as a model for advanced integrated cancer management in low-resource settings.
Authors: Pino Luis Eduardo , Franco Andrea Isabel 
Published: July 2024

e13783 Background: Cancer models are reactive, fragmented, and volume-based care, in which the lack of coordination between different layers of care, along with clinical and quality variability, technological pressure, and dominant positions, result in high levels of inefficiency and waste, affecting economic sustainability and hence effective access. This is prohibitive for low-resource settings. Modern healthcare system models in this scenarios should focus on solve this problems. Comprehensive cancer management needs a reorientation towards value- and efficiency-generating architectures.Usual redesigns have focused on direct cost containment through intensified audits or new contracting and payment modalities between stakeholders. However, the real impact of these strategies is marginal, increasing sectoral mistrust and failing to meet the quintuple aim. PENTA is a comprehensive cancer management framework to optimize cancer patient care, with emphasis on clinical governance, data guidance, and clinical-administrative alignment. This is an operational model for stakeholders in low-resource settings. PENTA model has been successfully implemented in health insurance companies in Colombia and in private insurance branch in Peru. Methods: PENTA has been applied since 2020. We employed a work methodology based on the Agile-2 matrix, which allows for fluidity and lower resource consumption. This methodology is hybrid and its execution begins with an initial diagnosis of the process within the partner company. This diagnosis includes prioritizing interventions from each of the axes, but understanding that this is a systemic project that includes 5 fundamental axes. This axes must be worked on simultaneously and interdependently to achieve the greatest value. Axes are: 1. Smart Risk Management, 2. Advanced Clinical Gobernance, 3. Value Audit, 4. Technology Management and 5. Value-based Contracting Focus on managing inefficiencies and waste (optimization model), PENTA can generate early results across various dimensions such as clinical variability and technology costs. Structuring and using a cross-cutting data architecture is fundamental to the model's development into a data control tower. Results: Implementation of a data control tower for cancer cohorts , development of joint clinical pathways (insurer-payer) for prioritized diseases, clinical practice agreements with hierarchical positions on high-cost medications, implementation of mini health technology assessments (HTAs), and generation of new prospective payment modalities based on performance adjustment. The estimated savings generated are $1.5 million for the phase 2 in Colombia and $800,000 for the phase 1 in Peru. Conclusions: PENTA is an agile framework for cancer management that can be sucessfully adapted to low-resource settings.
A paradox of size: Case-volume, financial outcomes, and risk in the enhancing oncology model baseline period.
Authors: Indurlal Puneeth , Thomas Hope Ives , Altieri Jason , Garey Jody S. , Neeb Jessica , Staggs Stuart George , Wilfong Lalan S. 
Published: July 2024

e13809 Background: The Centers for Medicare and Medicaid Innovation’s (CMMI) Enhancing Oncology Model (EOM) is a risk-bearing, population-based value-based care (VBC) model requiring participating physician group practices (PGP) to take financial risk and performance accountability for episodes of care for seven common cancers. We studied the association between case volume, financial outcomes, and risk in the EOM. Methods: Using deidentified public use EOM baseline episode files (2016 - 2020), and the EOM Price Prediction Model provided by CMMI, we calculated the predicted baseline price (BP) per episode and savings (difference between baseline price and actual expenditures (AE)), grouped PGPs per baseline period by episode count (case volume), and evaluated the risk (variation of savings). ANOVA, F-test, and pair-wise tests were used to evaluate statistical significance. Results: Two-thirds of the 16,348 PGP appearances per time-period (n) had <72 episodes (average: 93.8, median: 36). Table 1 shows population and savings metrics. There was a significant effect of episode counts on savings (ANOVA/F-test: F(5,16342) = 24.5, p<0.0005). Post hoc pair-wise t-tests (Holm correction to adjust p) indicated groups with <72 episodes had increased risk (4.5:1, p<0.0005) and >361 episodes had the least risk (p<0.0005). Groups with <72 episodes had four times the median savings than groups with >361 episodes. Conclusions: As expected with the law of large numbers, groups with fewer episodes are exposed to higher risk and extremes of financial outcomes in EOM-like models while paradoxically generating better savings. The impact of case-mix differences among groups is apt for further exploration. Differences in PGP dynamics and provider like-mindedness with care transformation is one possible explanation for this paradox. Future models should incorporate risk mitigating modeling techniques (case-volume adjustments) or facilitate easier partnering arrangements to engage groups with fewer episodes. [Table: see text]
Impact of gadopiclenol on decision making in patients with brain metastases: A post-hoc study.
Authors: Giordano Frank Anton , Fleckenstein Jens , Eckl Miriam , Stieler Florian , Bendszus Martin , Essig Marco , Wenz Frederik , Sarria Gustavo R. 
Published: July 2024

e14003 Background: Gadopiclenol (Elucirem, Guerbet, France) is a new high relaxivity macrocyclic gadolinium-based contrast agent (GBCA), recently approved by the FDA and EMA at the dose of 0.05 mmol/kg. The aim of this post-hoc analysis was to evaluate the impact of contrast-enhanced MRI with gadopiclenol at 0.1 mmol/kg on decision making and radiotherapy (RT) treatment planning of brain metastases (BM). Methods: This is a post-hoc analysis of data from a phase IIb study where patients underwent two separate MRI examinations, one with gadopiclenol at 0.025, 0.05, 0.1 or 0.2 mmol/kg and one with gadobenate dimeglumine at 0.1 mmol/kg. MR images of patients who received both GBCAs at 0.1 mmol/kg, with ≥1 BM detected in either of the scans, were subjected to a blinded reader analysis and contouring by two radiation oncology experts. For each patient, treatment plans (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]) were determined for both MRIs, with the gross target volume (GTV) indicating the contrast-enhancing aspects of the tumor. Mean GTVs and normal tissue volumes receiving 12 Gy (V12), as well as the Dice similarity coefficient (DSC) were obtained for the paired contours. The Spearman´s rank (ρ) correlation was additionally calculated. Furthermore, three experts blindly evaluated the contrast enhancement of each lesion for contouring purposes and subjectively qualified them as “better”, in detriment of the counterpart, or “equal”. Results: In total, images from 13 adult patients were analyzed. MRI with gadopiclenol depicted additional BM as compared with gadobenate dimeglumine in 7 patients (54%). The treatment plan was changed in 2 patients (15%), from no treatment to SRS and from SRS to WBRT. Gadopiclenol depicted additional BM in these 2 patients (from 0 and 10 BM with gadobenate dimeglumine to 1 and 15 BM with gadopiclenol). The mean GTVs and V12 were comparable between gadopiclenol and gadobenate dimeglumine (p=0.694, p=1.974). The mean DSC was 0.70 (SD: 0.14, ρ0.82). From a total of 36 answers, contrast enhancement was qualified as better with gadopiclenol in 21 (58.3%) evaluations, better with gadobenate dimeglumine in 8 (22.2%) evaluations, while no difference was observed in 7 (19.4%) evaluations. Conclusions: Gadopiclenol at 0.1 mmol/kg improved BM detection and contrast enhancement with potential impact on RT treatment decisions.
The clinical significance and expression of MAGE-A3 in patients with esophageal squamous cell carcinoma.
Authors: Wang Lan , Zuo Jing , Wang Yudong , Feng Li , Fan Zhisong , Wang Long , Han Jing , Zhang Xue , Liu Jiayin , Li Dan , Jin Hui 
Published: July 2024

e16065 Background: More than half of esophageal cancer patients are diagnosed as advanced, and although immunotherapy has shown strong anti-tumor activity in esophageal cancer patients, the survival benefits are limited. Melanoma-associated antigen 3 (MAGE-A3) is a cancer testis antigen that is almost not expressed in normal tissues, but highly expressed in various malignant tumors, including esophageal cancer. MAGE-A3 has restrictive expression and good immunogenicity, making it an ideal immunotherapy target. This study aims to explore the expression and clinical significance of MAGE-A3 in esophageal squamous cell (ESCC) . Methods: 103 ESCC tissues and 77 adjacent cancerous tissues were collected, and the expression of MAGE-A3 was detected using immunohistochemistry. Furthermore, the relationship between MAGE-A3 and clinical pathological features was analyzed, and the prognostic significance of MAGE-A3 for ESCC patients was analyzed with overall survival (OS) as the endpoint. Results: The positive expression rate of MAGE-A3 in ESCC tissue was 68.0% (70/103), and the positive expression rate in adjacent tissues was 7.8% (6/77). The positive expression in ESCC was significantly higher than that in adjacent tissues. In ESCC, the expression of MAGE-A3 is associated with age, pathological grade, TNM staging, and lymph node metastasis. Both univariate and multivariate analyses showed that the expression of MAGE-A3 is an independent risk factor affecting the prognosis of ESCC patients. The high expression of MAGE-A3 predicted poor OS for ESCC patients. Conclusions: MAGE-A3 is highly expressed in ESCC and is associated with poor prognosis, and could be a potential prognostic marker and therapeutic target.
Sintilimab combined with definitive chemoradiotherapy in locally advanced esophageal squamous cell carcinoma: A single-arm, multicenter, phase 2 trial.
Authors: Lyu Jiahua , Li Tao , Liang Long , Li Churong , Jia Hongyuan , Qi Yunxiang , Zheng Xiumei , Fan Yu , Kuang Hao , Bai Hansong , Zhang Wanli , Lu Guangbing , Wang Gan 
Published: July 2024

e16120 Background: Sintilimab is a PD-1 inhibitor that is approved for the treatment of advanced esophageal squamous cell carcinoma, but its efficacy and safety in locally advanced disease is unclear. We administered sintilimab with definitive chemoradiotherapy to patients with unresectable locally advanced oesophageal squamous cell carcinoma, and aimed to investigate the efficacy and safety of this treatment pattern. Methods: We conducted a multicenter, phase 2 trial at three cancer centers in sichuan province. Patients aged 18-75 years with untreated, unresectable, stage II-IVA esophageal squamous cell carcinoma, with an ECOG performance status of 0-2, and adequate organ and bone marrow function were eligible for inclusion. Patients received concurrent thoracic radiotherapy (60·0 Gy in 30 fractions), chemotherapy (two cycles of intravenous Albumin-Bound Paclitaxel [180 mg/m2, day1] and cisplatin [25 mg/m2, day1-3]), and Sintilimab (200 mg intravenously every 3 weeks for up to 1 year, or until disease progression or unacceptable toxicity). The primary endpoint was the progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate, quality of life (not reported here), and safety. The trial is registered with ClinicalTrials.gov, NCT046 02013. Enrolment is completed and follow-up is ongoing. Results: Between Oct 19, 2020, and Dec 08, 2023, 52 patients were enrolled. The median age was 65 years (IQR 58-71), 11 (21.1%) of 52 patients had stage IVA disease, and 49 (94.2%) patients were male and 3 (5.8%) were female. 50 (96.2%) of 52 patients patients completed the planned chemoradiotherapy. After a median follow-up of 15.0 months (IQR 7·9-28·0), the median PFS was not reached. The 1-, 2- and 3-year OS rates were 93.7%, 84.0% and 45.0%, respectively.The most common grade 3 or worse adverse event was neutropenia (23 [44.2%] of 52). Eight (15.4%) had treatment-related pneumonitis, but no patient died. Conclusions: Combining toripalimab with definitive chemoradiotherapy provided encouraging activity and acceptable toxicity in patients with locally advanced oesophageal squamous cell carcinoma, and this regimen warrants further investigation. Clinical trial information: NCT04602013 .
Analysis of ctDNA assay as a strategy for watchful waiting in locally advanced esophageal cancer.
Authors: To Hao Q. Q , Menon Harry , Green Garrett Barnard 
Published: July 2024

e16126 Background: Standard treatment for locally advanced esophagogastric (EG) cancer is neoadjuvant chemoradiotherapy (CRT) followed by surgery. The treatment goal is curative in order to control the tumor in the thorax, prevent regional recurrence, and to help prevent or delay metastatic progression. Despite achieving pathologic complete response (pCR) after surgery, patients with supposed local control may have recurrence up to a third of the time. Circulating tumor DNA (ctDNA) is an evolving tool in the field of oncology used as an informative biomarker. We provide longitudinal, real world observation of ctDNA minimal residual disease (MRD) to predict pCR and risk of recurrence. Methods: 22 participants with newly diagnosed locoregional EG cancer were enrolled under single institution approved protocol [IRB#1864127-7]. CtDNA-based MRD levels were obtained by Natera SignateraTM bespoke mPCR-NGS assay. Additionally, Natera Altera TM was used as a non-invasive biopsy to provide the comprehensive tumor-specific genomic profile. We evaluated thirteen participants who underwent definitive surgery and those who did not. Non-invasive plasma samples were surveilled at various timepoints which included the time of diagnosis, during neoadjuvant CRT, after definitive surgery. The primary outcome is a comparison of assay recurrence (AR) to disease recurrence (DR) defined as radiologic or clinical disease recurrence in participants with locoregional disease. Exploratory endpoints examine the profile of tumor. Results: Baseline levels were detected (n = 22) at new diagnoses. Longitudinal results demonstrated ctDNA clearance in eight participants while undergoing neoadjuvant chemoradiaton. Residual ctDNA were found in five participants for which two had clinical disease recurrence. Esophagectomy was done in three participants achieving pCR. Post procedural ctDNA were detected in one participant. Conclusions: The clearance of ctDNA favors less clinical disease recurrence in this study. This may indicate that ctDNA clearance confers lower risk of relapase. However, a larger cohort prospective study will be needed to validate the application of ctDNA as an early biomarker. The future application of ctDNA can be used to identify patients who may benefit from a watchful waiting adjuvant strategy instead of proceeding with invasive esophagectomy.
Effects of Attractive Pickering emulsion gels loaded with oxaliplatin and lactate dehydrogenase inhibitors in hepatocellular carcinoma.
Authors: Ye Chanqi , Chen Ruyin , Li Qiong , Xu Shuaishuai , Ruan Jian 
Published: July 2024

e16235 Background: Oxaliplatin (OXA) can be used as a palliative treatment for advanced hepatocellular carcinoma (HCC). While most patients still have rapid disease progression after OXA due to the drug resistance. The lactate dehydrogenase A (LDHA) inhibitors can reduce the inflammation-induced effects, metastasis, and proliferation potential of cancer cells. The combination of OXA and LDHA inhibitor may be an effective treatment for HCC. Methods: We adopt the water-in-oil attractive Pickering emulsion gel (APEG) to deliver OXA and LDHA inhibitor, GSK2837808A (GSK). OXA is dissolved in water and GSK is dissolved in iodized oil. We injected OXA+GSK@gel into the peritumoral tissues of subcutaneously tumorigenic HCC model mice, then observe the tumor size. Next, we apply immunohistochemical staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay on the dissected tumors to explore the cell proliferation and apoptosis. Meanwhile, flow analysis on the dissected tumors is applied to investigate the tumor immune microenvironment in HCC. Results: This drugs-loaded APEG has good biocompatibility and can release OXA and GSK slowly. OXA+GSK@gel has significant anti-tumor effect on HCC model, which can effectively inhibit tumor cell proliferation and promote tumor cell apoptosis. Meanwhile, flow analysis confirm that it could activate the tumor immune microenvironment in HCC. The infiltration of CD8+ T cells was increased, thereby providing better anti-tumor effect. Conclusions: The results suggest that the APEGs loaded with OXA and GSK can effectively improve the delivery efficiency and enhance the anti-tumor therapy.
Laparoscopic versus open hepatectomy for exophytic hepatocellular carcinoma: A multicenter propensity-matched comparative study.
Authors: Kongying Lin , Diao Yong-Kang , Huang Bin , Lv Guo-Yue , Wang Xian-Ming , Gu Wei-Min , Chen Zhong , Liang Ying-Jian , Jia Hang-Dong , Wang Hong , Chen Ting-Hao , Tang Shi-Chuan , Xu Jia-Hao , Wang Ming-Da , Shen Feng , Zeng Yong-Yi , Yang Tian 
Published: July 2024

e16268 Background: As laparoscopic hepatectomy (LH) gains traction in the surgical management of hepatocellular carcinoma (HCC), its efficacy for exophytic HCC, a subtype with unique surgical challenges, remains under scrutiny. This study aims to compare the long-term outcomes of LH with traditional open hepatectomy (OH) in treating exophytic HCC. Methods: A multicenter retrospective analysis was conducted on patients with solitary exophytic HCC undergoing LH or OH at 10 hepatobiliary centers. Propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were employed to balance the LH and OH groups for overall survival (OS) and recurrence-free survival (RFS) comparisons. Multivariable Cox-regression analysis determined the independent impact of surgical approach on OS and RFS. Results: The study included 270 patients, with 132 undergoing OH and 138 LH. Post-PSM, 97 matched pairs were analyzed. In this cohort, LH was associated with significantly lower 5-year OS (36.1% vs. 53.5%, P = 0.021) and RFS (31.7% vs. 44.9%, P = 0.013) compared to OH. Additionally, LH patients exhibited a higher rate of abdominal seeding metastases (19.6% vs. 8.2%, P = 0.023). Multivariable analysis in the PSM cohort revealed LH as an independent factor for reduced OS (HR, 1.62; 95% CI, 1.06-2.47; P = 0.025) and RFS (HR, 1.79; 95% CI, 1.22-2.64; P = 0.003), corroborated by IPTW cohort findings. Conclusions: This study indicates that LH may be less favorable than OH for exophytic HCC, potentially contraindicating its use in such cases. These findings highlight the necessity for further prospective research to refine surgical protocols for exophytic HCC.
Long-term follow-up of patients with hairy cell leukemia treated with different modalities at a single institution: Real-life experience over 25 years.
Authors: Khan Muneer , Meseeha Marcelle , Richards Julie L. , Poulose Joyson , Talamo Giampaolo 
Published: July 2024

e19023 Background: Hairy cell leukemia (HCL) is an uncommon and indolent leukemia of mature B cells, accounting for 2% of all lymphoid neoplasms. We analyzed characteristics, treatment modalities, response rates, and survival of HCL patients followed at our institution. Methods: We retrospectively reviewed data from the medical records of 56 consecutive HCL patients evaluated in our Hematology/Oncology clinic between 1998 and 2023. Results: The median age at diagnosis was 59 years (range, 37-94). Forty-nine patients (87%) were male. First-line therapy was cladribine in 30 patients (54%), cladribine + rituximab in 6 patients (11%), observation in 5 patients (9%), and another modality (fludarabine, pentostatin, single agent-rituximab, and other) in the rest of patients. The median follow-up was 122 months (1-291). The overall response rate was 96%. CR and PR rates were 68% and 28%, respectively. Relapses were observed in 44% of patients. The median OS was not reached, and the median PFS was 181 months (95% CI, 128-252). The 5-year and 10-year PFS were 78% and 29%, respectively. Only 3 patients (5%) died as a result of HCL, either indirectly from immune suppression (pneumonia, 2 patients) or directly (cachexia in 1 patient, untreated because of advanced age and comorbidities). Conclusions: Treatment with purine analogues such as cladribine, plus or minus rituximab, achieves deep and durable responses in most HCL patients. Although relapses were commonly observed, the vast majority of HCL patients did not die as a result of HLC.