tbuckley/cabot-search huggingface dataset:
A phase Ib/IIa study of DX1002, a novel drug in patients with pretreated advanced hepatocellular carcinoma: Efficacy and safety analysis.
Authors: Min Yuan, Zhuqing Liu, Xianling Guo, Qing Xu
Journal: Journal of Clinical Oncology (2024)

3122 Background: Advanced hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options. DX1002 is a novel, specific, small-molecule, tubulin inhibitors, that targets the beta subunit of tubulin in tumor vascular endothelial cells. It has been designed to destroy tumor blood vessels which has been demonstrated in preclinical efficacy models. The objectives of this trial were to assess safety, tolerability and preliminary efficacy of DX1002 in patients (pts) with pre-treated advanced HCC or gastric cancer. Here, we present the results from the HCC subpart. Methods: This is a prospective, single-arm open-label multi-center phase Ib/IIa trial (CTR2400080296) to investigate DX1002 in patients with pre-treated advanced HCC or gastric cancer. Patients received DX1002 600 mg orally once daily, continuously in 28-day cycles until progressive disease or intolerable toxicity. Primary endpoints were safety and objective response rate (ORR); other endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), pharmacokinetics and safety. Results: From Jun-2021 to Jan-2024, 40 patients with advanced HCC were enrolled. The median age was 54 (36-71) years. As of 31-Jan-2024, of the 40 pts, 4 pts (10.0%) showed PR and 15 (37.5%) had SD. ORR was 21.1% and DCR was 47.5%. The median PFS was 3.55 (95% CI 2.89-8.31) months and median OS was 13.4 (95% CI 11.0-NA) months. Any-grade TRAEs occurred in 75% pts (30/40), with 22.5% Grade 3 (9/40). The most common TRAEs were Aspartate aminotransferase increased (22.5%), total bilirubin increased (20%), albuminuria (20%), Hypoalbuminemia (15%) and gamma-glutamyl transferase increased (15%). Four patients (10%) discontinued DX1002 due to TRAEs. No death-related cases occurred. Conclusions: Initial data shows DX1002 demonstrated manageable safety profile and promising anti-tumor potential in pre-treated advanced hepatocellular carcinoma. Further exploration of DX1002 in HCC is warranted. Clinical trial information: ChiCTR2400080296.
The reduction of LEDD leads to visual dysfunction in patients with PD after STN-DBS: a randomized clinical trial
Authors: Jinxing Sun, Shengmei Ma, Zhenke Li, Junheng Jia, Qianqian Wu, Ying Hou, Hong Wang, Qi Wang, Guangjian Zhang, Zhimin Zhao, Bin Huang, Xiangyu Ma, Xingang Li, Weiguo Li, Chao Zhang
Journal: International Journal of Surgery (2024)

Medication adjustment after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD) may influence visual function. However, no clinical trials have been designed specifically to investigate this effect. To compare the effects of levodopa-equivalent daily dose (LEDD) reduction and non-reduction on visual function in patients with Parkinson's disease (PD) following STN-DBS. This was a multi-center, prospective, randomized, double-blinded clinical trial. A total of 208 patients with Parkinson's disease were referred for DBS between June 2019 and July 2021 and analyzed between June 2023 and July 2023. STN-DBS was performed, and the LEDD was reduced in one study arm but not in the other. The primary outcome measure was visual impairment in Parkinson's disease questionnaire (VIPD-Q) with or without LEDD reduction 12 months postoperatively, and the secondary outcomes included retinal nerve fiber layer (RNFL) thickness, vessel density, eye-tracking system results, contrast sensitivity and visual field. During the short-term follow-up, DBS implantation and stimulation did not significantly affect visual function (VIPD-Q, baseline vs. 1 month, 9.269±8.385 vs. 8.938±7.666, Mann-Whitney U tests; P=0.6746). In the long-term follow-up, the reduction group demonstrated a significant decline in visual function, RNFL thickness, and vessel density after STN-DBS compared with the control group without STN-DBS (P<0.001). Visual dysfunction, particularly a thinner RNFL and lower vessel density, is related to LEDD reduction after STN-DBS. Prolonged administration of dopamine-mimetic drugs prevents visual symptoms. Thus, physicians should consider LEDD adjustment when patients report visual dysfunction before surgery or severe visual symptoms after STN-DBS.
Effect of perioperative medical therapy on prognosis in recurrent nasopharyngeal carcinoma: A comparative effectiveness research.
Authors: Xiaole Song, Hongmeng Yu, Li Yan, Xiaoshen Wang, Huankang Zhang
Journal: Journal of Clinical Oncology (2024)

e18051 Background: Transnasal endoscopic (TEN) surgery has evolved to be an important treatment for rNPC.The role of perioperative chemotherapy or immunotherapy has not been determined yet. Methods: Three single arm, prospective researches were pooled to analyze the comparative effectivenessof neoadjuvant, adjuvant therapy and surgery only in rNPC patients undergoing TEN surgery through 2019 to 2023. Data was collected including sex, age, TNM staging, treatment modality and internal carotid artery (ICA) management in three investigator initial trials (NCT05011227, ChiCTR1900026341, NCT05350891). The primary and secondary outcomes were overall survival (OS) and local recurrence free survival (LRFS). Statistical analysis was performed using SPSS 29.0 (IBM).Variables with two-sided P-values &lt;0.05 in log-rank tests were identified as significant. Multivariable Cox regression analysis was conducted to reveal the prognostic value of treatment modality. Results: Overall, 233 eligible participants were divided into three treatment groups (neoadjuvant, adjuvant, and surgery only group). The clinicopathological characteristics were balanced (Table). In a mean follow-up period of 605 days, the 1-year, 2-year OS rate were 91.9%, 83.3% respectively. According to Kaplan Merier survival analysis, immunotherapy± chemotherapy after surgery significantly improved OS compared with surgery only (P&lt;0.001). Although no significance (P=0.176) was noted in neoadjuvant compared with surgery only group, partially because of the small sample size, the 1-,3-year OS rate was much higher. When blended together, neoadjuvant+adjuvant group also won over surgery only group regarding OS (P&lt;0.001) and LRFS (P=0.002). Subgroup analysis also indicated that age≥52 (P=0.002), higher T staging (P&lt;0.001), and embolization of ICA (P&lt;0.001) were associated with worse prognosis. Sex showed no significant effect on survival (P=0.533). The above four factors were adopted for multivariate COX analysis, elucidating that age (P=0.005), T staging (P=0.024) and treatment modality (P=0.007) were independent predictor for OS, however, embolization of ICA (P=0.097) was not. Conclusions: Adjuvant therapy, as an independent predictor of OS, improved the overall survival in rNPC patients underwent TEN surgery. The efficacy of neoadjuvant therapy demanded solid evidence from larger sample size cohort. Clinical trial information: NCT05011227 , NCT05350891 , ChiCTR1900026341. [Table: see text]
Sacubitril/Valsartan Versus Enalapril in Chronic Chagas Cardiomyopathy
Authors: Edimar Alcides Bocchi, Luis E. Echeverria, Caroline Demacq, Pedro Gabriel Melo de Barros e Silva, Lilian Mazza Barbosa, Lu-May Chiang, Lucas Damiani, Carlos A. Morillo, Ruben Kevorkian, Felix Ramires, M. Cecilia Bahit, Ariana Ferrari, Adolfo Chavez-Mendoza, Jose Antonio Magaña-Serrano, John J.V. McMurray, Claudio Gimpelewicz, Renato D. Lopes
Journal: JACC Heart Failure (2024)

Chronic Chagas cardiomyopathy (CCC) has unique pathogenic and clinical features with worse prognosis than other causes of heart failure (HF), despite the fact that patients with CCC are often younger and have fewer comorbidities. Patients with CCC were not adequately represented in any of the landmark HF studies that support current treatment guidelines. PARACHUTE-HF (Prevention And Reduction of Adverse outcomes in Chagasic Heart failUre Trial Evaluation) is an active-controlled, randomized, phase IV trial designed to evaluate the effect of sacubitril/valsartan 200 mg twice daily vs enalapril 10 mg twice daily added to standard of care treatment for HF. The study aims to enroll approximately 900 patients with CCC and reduced ejection fraction at around 100 sites in Latin America. The primary outcome is a hierarchical composite of time from randomization to cardiovascular death, first HF hospitalization, or relative change from baseline to week 12 in NT-proBNP levels. PARACHUTE-HF will provide new data on the treatment of this high-risk population. (Efficacy and Safety of Sacubitril/Valsartan Compared With Enalapril on Morbidity, Mortality, and NT-proBNP Change in Patients With CCC [PARACHUTE-HF]; NCT04023227)
Neoadjuvant tislelizumab plus chemotherapy followed by salvage surgery and adjuvant tislelizumab for recurrent head and neck squamous cell carcinoma after radiotherapy: A single-arm, phase II trial.
Authors: Wenjie Wu, Lin Wang, Tong Zhang, Jie Zhang
Journal: Journal of Clinical Oncology (2024)

6070 Background: Locoregional recurrence remains a significant challenge in head and neck squamous cell carcinoma (HNSCC) after surgery and radiotherapy. Salvage surgery is the best option if negative margins can be achieved, and this can be strengthened in the era of immunotherapy. However, some relevant questions remain unanswered. The objectives of this prospective study were to evaluate the efficacy and safety of neoadjuvant tislelizumab plus chemotherapy followed by salvage surgery and adjuvant tislelizumab for recurrent HNSCC after radiotherapy. Methods: In this phase II, single-arm study, eligible pts 18 years of age or older with locoregional recurrent HNSCC after radiotherapy received neoadjuvant therapy with tislelizumab (200 mg), albumin-bound paclitaxel (260 mg/m 2 ), and cisplatin (60-75 mg/m 2 ) Q3W for 2 cycles, followed by salvage surgery and adjuvant tislelizumab (200 mg) Q3W for 6 cycles. The primary endpoint was major pathologic response (MPR) rate. Secondary endpoints included pathological complete response (pCR) rate, objective response rate (ORR), event-free survival (EFS), overall survival (OS) and safety. Results: Between March 2022 and September 2023, 34 pts were enrolled. Median age was 56 (30-75) yrs, 20.6% smoking history, 20.6% alcohol history and 61.8% male. All pts completed neoadjuvant therapy with an ORR of 35.3% (12/34) and DCR of 94.1% (32/34). Twenty-six pts (23 OSCC, 3 OPSCC) successfully underwent surgery with MPR rate 19.2% (5/26), of which the pCR rate was 15.4% (4/26). At median follow-up of 15.1 months, 1-year EFS was 63.4% and 1-year OS was 82.5% for per-protocol population. Twenty-five pts complained symptoms included pain, trismus, dysphagic, and speech disorders at baseline visit, and 84% (21/25) achieved remission after 2 cycles of neoadjuvant therapy. Grade 1-2 adverse events (AEs) with an incidence greater than 10% include 94.1% alopecia, 38.2% fatigue, 35.3% anorexia, 17.6% hypothyroidism and 14.7% anemia. Grade 3-4 adverse events (AEs) occurred in 1 pts (2.9%) with G3 hyperglycemia. Conclusions: Neoadjuvant and adjuvant tislelizumab with salvage surgery is well tolerated. The 1-year EFS and OS compared favorably with historical data. These encouraging results warrant further investigations. Clinical trial information: ChiCTR2100054296.
Neoadjuvant immuno-chemo-radiotherapy in operable esophageal and gastroesophageal junction adenocarcinoma with carboplatin, paclitaxel plus radiotherapy and avelumab (anti-PDL1 antibody): Neo-CREATE trial.
Authors: Amitesh Chandra Roy, Tim F Bright, Nimit Singhal, Matthew E. Burge, Eva Segelov, Andrew Mark Haydon, Lorraine A. Chantrill, Michael Michael, Caroline Connell, David Moffat, Richard John Woodman, Michael Michael, Erin Symonds, Timothy Jay Price, Alex Scott-Hoy, Alison Richards, Christos Stelios Karapetis
Journal: Journal of Clinical Oncology (2024)

4086 Background: Neoadjuvant CROSS regimen followed by adjuvant nivolumab or perioperative FLOT are current standards of care for patients with curable esophageal/ gastroesophageal (GEJ) junction adenocarcinoma. We hypothesized that adding avelumab to neoadjuvant chemo-radiation (CRT-A) before surgery can further improve outcomes. Methods: Patients with cT1-3 and N0/N1 M0 esophageal or GEJ adenocarcinomas eligible for curative surgery received weekly carboplatin and paclitaxel concurrently with radiotherapy (41.4 Gy in 23 fractions) and bi-weekly avelumab (5 doses). The trial had a run-in phase of 10 patients to evaluate feasibility and safety and a planned futility analysis after 15 patients have undergone surgery. The primary endpoint was pathological complete response (pCR) (Mandard criteria) by central pathology review, secondary endpoints were major histological response and survival outcomes. Using an A’hern single stage design for efficacy forty-seven patients were required to rule out a lower limit of a 20% pCR rate (p0) and to demonstrate an increase to a 40% pCR rate (p1), with 90% power and significance level α=0.05. Tissue, blood, and stool samples were collected for corelative analysis. Results: 48 patients were enrolled between Sept 2019 to Oct 2022 across seven Australian sites. Median age 65 [44-81], 95% were male (n=45), with majority of cancers being esophageal/GEJ type I (n = 35), with GEJ type II (n = 13). Forty-seven (97%) patients completed CRT -A and 46 (95%) had surgery. CRT-A was well tolerated, with two patients having &gt; grade 2 adverse event of interest in the form of myocarditis attributed to avelumab. Notable toxicities included grade 2-4 myocarditis (4%), anastomotic leak (4%), infection (6%) and diarrhoea (6%). In 44 evaluable patients, pCR was 23%. MHR was 58.3% (95% CI, 43.3%-72.1%), complete or near complete response (Tumor Regression Grade 1-2) was 31%. Overall, 1-yr disease free survival was 83.8% and OS was 91.2%. 1-yr disease free survival was 91.7% for patients with MHR vs 73.3% without MHR, p=0.20. Conclusions: Combining avelumab with neoadjuvant CRT is feasible in patients with acceptable tolerability in locally advanced esophageal/ GEJ adenocarcinoma. Avelumab with CRT is active however observed pCR rate does not represent a signal of substantial improvement compared to historical controls. Exploratory analysis suggests improved outcomes in patients with optimal tumour regression after neoadjuvant CRT-A. Exploratory biomarker work to corelate with outcomes is underway. Clinical trial information: ACTRN12619000288123.
Efficacy and safety of fruquintinib plus investigator's choice of chemotherapy as second-line therapy in metastatic colorectal cancer: Updated results of a multicenter, single-arm, phase 2 trial.
Authors: Wensi Zhao, Jun Li, Liping Li, Junping Huang, Wei Gong, Xiongjie Yu, Kefa Le, Linli He, Qi Han, Songlin Wang, Ze Tang, Wenbin Li, Xianliang Hua, Yongshun Chen
Journal: Journal of Clinical Oncology (2024)

3571 Background: Fruquintinib, a potent and highly selective vascular endothelial growth factor receptor (VEGFR) inhibitor, combined with investigator’s choice of chemotherapy as second-line therapy in patients (pts) with metastatic colorectal cancer (mCRC) showed promising efficacy in preliminary analysis (2023 ASCO Poster-3582) of the prospective, open-label, multicenter, single-arm phase 2 trial (ChiCTR2200059280). Here we reported the updated efficacy data. Methods: Pts with mCRC progressed after first-line prior systemic treatment were administered fruquintinib (5~3 mg, d1-21, q4w) and investigator’s choice of chemotherapy (fluorouracil ± irinotecan ± oxaliplatin, d1, q3w) for up to 8 cycles. Patients without disease progression (PD) were followed by fruquintinib maintenance until PD or unacceptable toxicities. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), overall survival (OS) and safety. Results: From November 2021 to November 2023, 100 pts were enrolled. Median age was 63 years (IQR, 56.5-71) and 61.0% were male. The left colon cancer involved in 77.0% pts. All pts had MSS/pMMR phenotype and 37.0% had RAS/BRAF-mutated tumors. 9.0% received prior anti-EGFR and 55.0% received anti-VEGF therapy. Most common sites of metastatic disease were liver (57.0%) and lung (41.0%). As of January 20, 2024, with a median follow-up of 9.3 mo, the median PFS was 6.9 mo (95%CI, 5.2-8.6), median OS was 20.1 mo (95%CI, 13.7-26.3). ORR was 26.0% (95%CI, 17.9-36.2), DoR was 11.3 mo (95%CI, 8.6-14.0), and DCR was 83.3% (95%CI, 74.0-89.9) in 96 efficacy-evaluable pts. The incidence of adverse events was comparable to the known toxicities associated with fruquintinib and chemotherapy. No treatment-related deaths occurred. Grade 3/4 adverse effects occurred in 33 pts (33.0%), and most commonly were neutropenia (21.0%), leukopenia (14.0%), thrombocytopenia (6.0%), proteinuria (5.0%), hypothyroidism (3.0%), diarrhea (2.0%), hand-foot syndrome (2.0%) and hypertension (1.0%). Conclusions: Fruquintinib combined with investigator’s chemotherapy followed by fruquintinib maintenance as second-line therapy showed satisfactory anti-tumor activity, prolonged PFS and OS, and manageable safety profiles in pts with mCRC. Further analysis of all pts with long-term follow-up will be presented in the future. Clinical trial information: ChiCTR2200059280.
Racial disparities and survival outcome of patients with locally advanced cervix cancer in the international randomised phase 3 OUTBACK trial (ANZGOG 0902, RTOG 1174, NRG 0274).
Authors: Yeh Chen Lee, Tara Castellano, Tashanna K. N. Myers, Elizabeth H Barnes, Dana Meredith Chase, Colleen McCormick, Katrina Diamante, Catherine M. Shannon, Warner King Huh, Jayanthi Sivasothy Lea, Joan L. Walker, William Small, Katherine Miller, Geetha Govindarajulu, Bradley J. Monk, Martin R Stockler, Kathleen N. Moore, Linda R. Mileshkin, Victoria Lin Bae-Jump
Journal: Journal of Clinical Oncology (2024)

1594 Background: OUTBACK was an international multi-center phase 3 trial investigating adjuvant chemotherapy following definitive chemoradiation in locally advanced cervix cancer. We analysed if baseline characteristics were associated with survival outcome. More specifically, we determined whether race held prognostic significance relative to established clinical factors. Methods: We compared baseline characteristics (encompassing demographics, biomarkers and participants’ self-ratings of EORTC QLQ-C30 scores) between racial groups using chi-squared tests. We then explored relationships between baseline characteristics and survival outcomes using univariable and multivariable Cox proportional hazards regression models with stepwise selection. Results: Black or African American participants accounted for 13% (n=121/919) of the OUTBACK study population. There were no evident differences in the proportion of Black or African American participants, as compared to other racial groups, across most baseline characteristics, except for country of residence (USA vs non-USA, p&lt;0.01). When examining the impact of race (Black or African American vs other racial groups) on survival outcomes in locally advanced cervix cancer, we found no evident associations with overall survival (HR 1.2; 95%CI,0.84 – 1.72; p=0.32) or progression free survival (HR 1.29; 95%CI, 0.95 – 1.75; p=0.10). Multivariable analysis identified several independent prognostic factors for overall survival, including performance status (HR 1.43; 95%CI, 1.04-1.95; p=0.03), FIGO stage (HR 2.02; 95%CI, 1.48-2.75; p&lt;0.01), nodal involvement (HR 1.59; 95%CI, 1.18-2.14; p&lt;0.01), and elevated white cell count (HR 1.68; 95%CI, 1.21-2.33; p&lt;0.01). Role function, social function, financial difficulties and eGFR showed significance in univariable analysis for overall survival but did not retain significance in multivariable analysis. These findings were consistent when examining progression-free survival. Conclusions: No discernible disparities in survival outcomes were observed between Black or African American participants and other racial groups undergoing primary treatment for locally advanced cervix cancer. The primary prognostic determinants for this disease continue to be cancer staging and clinical performance status. Enrolment into a clinical trial may have abrogated the historical disparities seen among ethnic and racial groups. Clinical trial information: 12610000732088.
Extracorporeal membrane oxygenation as life-saving bridge for patients with airway obstruction caused by neck and chest tumors to salvage procedure: an in-depth review
Authors: Shitong Su, Lianjing Liang, Zijian Liu, Ling Wang, Tong Zhang, Nianyong Chen
Journal: International Journal of Surgery (2024)

Narrowed or stenotic airways are frequently encountered in emergency practice. Neck and chest tumors-caused airway obstruction usually follow a severe clinical course, necessitating urgent ventilation as a bridge to perform emergency operations. In certain cases, traditional ventilation methods may not safely address complicated airway conditions. In such instances, special cardiopulmonary support becomes necessary to manage both hemodynamics and ventilation for patients. Extracorporeal membrane oxygenation (ECMO) is considered a last resort treatment for respiratory failure. When dealing with emergency difficult airway situations, ECMO offers certain advantages over conventional ventilation. However, its effectiveness in managing airway obstruction due to solid tumors located in the neck or chest is not well-established due to limited clinical practice. Published articles about this topic are still limited and primarily rely on case series and reports. As a result, they offer insufficient data and illustrations to fully elucidate emergency issues. In the present article, the authors summarize the existing literature concerning ECMO utility in managing patients with airway obstruction due to solid tumor located in the neck or chest based on PubMed, Web of Science, and other medical databases, to conduct an in-depth review. The authors conducted an analysis of 27 studies, including a total of 54 patients with airway obstruction caused by tumors. All patients underwent surgical relief of airway obstruction with ECMO as ventilatory support. Postoperatively, 87% of the patients (47/54) survived. 7.4% of the patients (4/54) died due to postoperative disease progression, unrelated to ECMO complications. The prognosis of 5.6% of the patients (3/54) could not be obtained. Additionally, the authors present an interesting case series (n=5) based on a real-world research to demonstrate the different outcomes among airway-obstructed patients due to neck and chest masses. In this series, four patients supported by ECMO were successfully discharged postoperatively, while one patient on conventional ventilation died due to respiratory collapse before surgery. Meanwhile, the authors share novel illustrations and clinical figures to supplement the understanding of this condition. The findings presented in this article provide a basis for further studies and can be used to improve management of the patients.