bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the efficacy of chemoradiotherapy combined with immunotherapy for local-regional recurrent esophageal cancer patients after esophagectomy: A retrospective analysis.
Authors: Xu Qicen , Feng Dongjie , Xu Youtao , Zhu Zihao , Chen Yu , Zhao Lijun , Kong Cheng , Jiang Ming , Li Ming , Jiang Ning , Zhu Xiangzhi 
Published: July 2024

e16085 Background: Chemoradiotherapy has been the standard-of-care for esophageal cancer patients with local-regional recurrent disease after esophagectomy without prior chemoradiation. Recent studies have demonstrated that immune checkpoint inhibitors confer survival benefits to patients with esophageal cancer. However, the effectiveness of chemoradiotherapy combined with immunotherapy remains undetermined in patients experiencing local-regional recurrence. Methods: Esophageal cancer patients treated at our institution were screened retrospectively for the following inclusion criteria: histological confirmation of squamous cell carcinoma; loco-regional recurrence after surgery-based first-line treatment; received chemoradiotherapy combined with immunotherapy regimen after loco-regional recurrence. Patients with prior radiotherapy were excluded. The endpoints of the study were overall survival (OS) and progression-free survival (PFS). Loco-regional recurrence was defined as recurrences from below the hyoid to the lower margin of the first lumbar vertebra, including supraclavicular, mediastinal, abdominal lymph nodes, and the tumor bed. PFS was defined as the time from the date of postoperative recurrence until disease progression, recurrence, death, or the last follow-up day; OS was determined as the duration from postoperative recurrence to the date of death from any cause or the last follow-up date. Results: Between January 2020 and July 2023, 685 patients were screened and 61 patients were finally enrolled in this study. The median follow-up period was 14 months (2.9~45.5 months). Regarding the regions of recurrence, 31 patients experienced exclusive mediastinal recurrence, and 30 patients had recurrence beyond the mediastinum (supraclavicular lymph node [n = 21], abdominal lymph node [n = 8], both supraclavicular and abdominal lymph node [n = 1]). In these cases, 26 patients (43%) experienced recurrence after receiving chemoradiotherapy combined with immunotherapy (loco-regional failure [n = 15], distant metastasis [n = 3], and both loco-regional failure and distant metastasis [n = 8]). Fourteen (23%) patients died from disease progression. The median PFS was 18 months (95%CI, 9.6-26.4) and the median OS was not reached. The 2-year OS rate was 65%. In univariate analysis, patients with recurrence in supraclavicular/abdominal lymph nodes had a worse prognosis (P = 0.014, HR = 2.765). Conclusions: Chemoradiotherapy combined with immunotherapy showed a favorable efficacy in radiotherapy-free esophageal cancer patients experiencing loco-regional recurrence post-surgery. Additionally, the regions of recurrence may influence patient outcomes.
Camrelizumab combined with apatinib as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: A phase 2 trial.
Authors: Meng Xiangrui , Qi Yu , Shan Zhengzheng , Yang Yang , Fan Qingxia , Wang Feng 
Published: July 2024

e16087 Background: Increasing evidences prove the encouraging efficacy of neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma (ESCC). However, the safety of chemotherapy is still unsatisfactory. Previous studies have confirmed the good efficacy and tolerance of PD-1 inhibitors combined with angiogenesis inhibitors in advanced ESCC. This trial is to assess the effectiveness and safety of camrelizumab (PD-1 inhibitor) plus chemotherapy or apatinib (angiogenesis inhibitor) as neoadjuvant therapy for locally advanced ESCC. Methods: This was an open-label, non-randomized phase 2 trial of patients with stage cT2-4aN0-3M0 ESCC. Eligible patients were 18-75 years old, had ECOG PS score of 0-1. Patients received 2 cycles (1 cycle per 4 weeks) of camrelizumab (200 mg Q2W) and apatinib (250 mg QD). Surgery was performed within 4-6 weeks after neoadjuvant therapy. The primary endpoint was major pathological response (MPR) rate. Secondary endpoints included pathological complete response (pCR) rate, R0 resection rate, disease-free survival (DFS), overall survival (OS), and safety. Results: Between Feb 2022 and Dec 2023, 24 patients (19 males and 5 females) with a median age of 67 years were enrolled in the study. Twenty-one patients completed neoadjuvant therapy, the ORR was 50% and the DCR was 95%. Nineteen patients completed surgery and all patients (100%) reached R0 resection, 3 patients (3/19, 10.5%) reached pCR, 8 patients (8/19, 42.1%) reached MPR, and 13 patients (13/19, 68.4%) had TNM downstaging. The median follow-up was 11.9 months, and the median DFS had not yet reached. Any grade and grade ≥3 adverse events occurred in 87.5% and 8.3% of 24 patients, respectively. The most common AEs were increased alanine aminotransferase (8/24, 33.3%), increased alanine aminotransferase (7/24, 29.2%) and thrombocytopenia(7/24, 29.2%). No new safety signals or treatment-related deaths were observed. Conclusions: Neoadjuvant camrelizumab in combination with apatinib in patients with locally advanced ESCC showed promising pathological response and downstaging effect with acceptable security. The study enrollment is ongoing, and further survival and safety data will be reported in the future. Clinical trial information: NCT03917966 .
Tislelizumab combined with chemotherapy or radiotherapy as neoadjuvant therapy for resectable esophageal squamous cell carcinoma (TINES): A randomized, open, phase II study.
Authors: Zhang Yong , Che Shaomin , Chen Nanzheng , Li Xinju , Fu Junke , Yu Chenao , Wang Tianren , Liang Runjia , Xu Haozhen , Wu Qifei , Jia Zhuoqi , Zhu Cailin , Gong Tuotuo , Li Haijun , Zhang Boxiang , Hu Yunyun , Liu Yaqi 
Published: July 2024

e16090 Background: Although immunotherapy combined with chemotherapy has gradually been confirmed to improve the resectable esophageal squamous cell carcinoma (ESCC), it is necessary to explore other safe and efficient combination regimens. Radiotherapy could induce immunosensitization to improve the efficacy of PD-1 blocker, this study evaluated the efficacy and safety of tislelizumab combined with radiotherapy in resectable ESCC. Methods: 32 treatment-naïve patients with resectable ESCC (T2-4aNanyM0) were planed and randomized (1:1) to two arms for neoadjuvant therapy. Arm A received tislelizumab (200 mg on day 1), paclitaxel (150 mg/m2 on day 1) and cisplatin (75 mg/m2 on day 1) once every 3 weeks for 3 cycles, and arm B received radiotherapy with 41.4 Gy in 23 fractions combined with 3 cycles (200 mg, Q3W) of tislelizumab. Surgery was planned in 4-6 weeks post neoadjuvant therapy. Postoperative adjuvant tislelizumab was given to arms A and B for up to 14 cycles. The primary endpoint was pathological complete response (pCR) rate. The secondary endpoints included major pathological response (MPR) rate, disease-free survival, overall survival and safety. Results: Between October 2022 to January 2024, 22 patients were enrolled: arm A (n = 12) and arm B (n = 10). 15 patients were male and 7 patients were female. The median age was 65 years (range, 37 to 75 years). 8 patients were in stage II, 13 were in stage III and 1 was in stage IV. 18 (81.8%) patients from arms A and B completed neoadjuvant therapy, and 10 patients underwent surgery, 6 patients were awaiting preoperative evaluation, still 2 surgery cancelations due to patient withdrawal for symptom improvement. The pCR rate was higher in arm B (25.0%, 1/4) compared to arm A (16.7%, 1/6). MPR rates were 83.3% and 75.0% for arms A and B. During neoadjuvant treatment, no grade 3-5 treatment-related adverse events were observed. Conclusions: Tislelizumab plus chemotherapy or radiotherapy as neoadjuvant therapy demonstrated encouraging therapeutic effect for resectable ESCC.
Age and body composition of patients receiving treatment for locally advanced esophageal cancer.
Authors: Ricker Ansley Beth , Robinson Jordan , Shea Reilly , Cockerham Katelyn , Simpson Matigan , Squires Malcolm Hart , Salo Jonathan C. 
Published: July 2024

e16094 Background: Standard of care for locally advanced esophageal cancer consists of chemoradiation (chemoRT) followed by esophagectomy. Fewer patients in older populations with locally advanced esophageal cancer undergo esophagectomy when compared to their younger counterparts. Furthermore, frail patients frequently forgo surgery after chemoRT. The current study examined the relationship between age, body composition, and treatment decision-making in locally advanced esophageal cancer. Methods: Patients with clinical stage T2-4, N0-2, and M0 adenocarcinoma or squamous cell carcinoma of the mid or distal esophagus diagnosed between 2010-2021 were included from 11 hospitals across our healthcare system. Treatment decision-points included receipt of chemoRT versus non-curative therapy, unresectable disease after chemoRT defined by metastatic disease or upper mediastinal lymphadenopathy, and receipt of surgery stratified by histology. Sociodemographic data including age, race, sex, insurance status, socioeconomic status, body composition data from CT imaging (skeletal muscle gauge [SMG]), and outcome data were collected. Skeletal Muscle Gauge was calculated as the product of skeletal muscle cross-sectional area at L3 normalized for height and muscle density. Fisher's exact test was used for categorical variables and Kruskal-Wallis for continuous variables. Results: 513 patients were included in the analysis, of which 399 (78%) had adenocarcinoma and 114 (22%) had squamous cell carcinoma. Median age was 66. Of the 513 patients, 472 (92%) underwent chemoRT (366 [78%] adenocarcinoma, 106 [22%] squamous cell carcinoma). Patients who were over the age of 75 were less likely to undergo chemoRT when compared to their younger counterparts (85% vs. 94%, p = 0.002). After the completion of chemoRT, 419 (89%) patients were deemed resectable, 330 adenocarcinoma and 89 with squamous cell carcinoma. Among resectable patients with adenocarcinoma, those > 75 years old and lower SMG were less likely to receive surgery (p < 0.001 and p =0.001). Age and body composition associated with lower receipt of surgery in locally advanced esophageal cancer patients was significant on both univariate and multivariate analyses. Conclusions: Patients over 75 are less likely to undergo chemoRT and surgical resection for locally advanced esophageal cancer. Among patients with resectable disease who have completed chemoRT, those with unfavorable body composition as measured by low SMG on CT imaging are also less likely to undergo surgical resection. These measures may be helpful in surgical decision-making in patients with locally-advanced esophageal cancer. Further study is warranted to more precisely define the relationship between age, body composition, and risk of surgery in esophageal cancer.
Neoadjuvant nivolumab plus paclitaxel/cisplatin- chemo-radiotherapy (neo-NTP-CRT) followed by esophagectomy for locally advanced esophageal squamous cell carcinoma (ESCC): A phase II study.
Authors: Huang Ta-Chen , Guo Jhe-Cyuan , Lin Chia-Chi , Kuo Hung-Yang , Chuang Chien Huai , Cheng Jason, Chia-Hsien , Hsu Feng-Ming , Lee Jang-Ming , Huang Pei-Ming , Ko Kuan-Yin , Hsu Chih-Hung 
Published: July 2024

e16098 Background: Adjuvant nivolumab has shown efficacy in reducing recurrence in patients (pts) with locoregional esophageal cancer harboring pathologic residual disease following neoadjuvant chemoradiotherapy (CRT). However, the efficacy of adding nivolumab to neoadjuvant CRT remains unclear. Methods: We conducted a phase II trial of neoadjuvant nivolumab (240mg IV on D-14, 1, 15, 29), paclitaxel (50mg/m2 IV on D1, 8, 15, 22, 29), cisplatin (30mg/m2 IV on D1, 8, 15, 22, 29) and RT (45Gy given in 25 fractions) followed by esophagectomy 6 to 8 weeks after finishing CRT in pts with locally advanced ESCC, defined as clinical stage cT3-4aN0M0 or cT1-3N1-3M0 according to the AJCC Cancer Staging System 8th ed. (ClinicalTrials.gov Identifier: NCT05130684). The study, in a Simon’s two-stage design, used pathological complete response (pCR) rate as the primary endpoint. Secondary endpoints included feasibility, safety, recurrence free survival (RFS), progression free survival (PFS), and overall survival (OS). Results: Between Jan 2021 and Apr 2023, we enrolled a total of 17 pts. Fifteen were male. The median age was 52 years (range: 44~69). The clinical stage was I, II, and III in 1, 1, and 15 pts, respectively. All pts received neo-NTP-CRT with the following dose-intensities (mean dose intensity [range]): nivolumab (95% [50%~ 100%]), paclitaxel (75% [48%~ 100%], cisplatin (97% [80%~ 100%]), and radiotherapy (100%). Fourteen pts received esophagectomy, and 4 of them achieved pCR (24%). Because pCR for the first stage did not meet the efficacy criteria to move forward to second-stage, the enrollment was discontinued after enrolling 17 pts. During neo-NTP-CRT, the most common treatment-related adverse events (TRAEs) were leukopenia (76%), neutropenia (59%), thrombocytopenia (35%), and skin rash (35%); and the most common grade 3 and 4 TRAEs were leukopenia (24%), neutropenia (6%), and nausea and vomiting (6%). Among 14 pts receiving esophagectomy, 4 experienced surgical complications, including 2 with anastomotic leakage, 1 with subclavian artery rupture, and 1 with pneumonitis; one pt died 263 days after surgery, followed by a prolonged hospital stay due to refractory anastomotic leakage, infectious complications, and tumor progression. The median follow-up duration was 18 months. Median RFS, PFS and OS was 8, 12, and 16 months, respectively. Conclusions: Our data indicate that adding nivolumab to neoadjuvant paclitaxel and cisplatin-based CRT is feasible but does not improve pCR rate in locally advanced ESCC pts. Clinical trial information: NCT05130684 .
Gender disparity in enrollment in clinical trials for hairy cell leukemia (HCL) in the last 40 years.
Authors: Borja Montes Oscar Felipe , Escobar Gil Tomas , Epperla Narendranath , Andritsos Leslie Ann 
Published: July 2024

e19024 Background: Hairy Cell Leukemia (HCL) is a B-cell lymphoproliferative disorder characterized by infiltration of the bone marrow, liver, and spleen by malignant B cells with hairy cell cytoplasmic projections(1). There is a significant predominance of HCL in males, with a male-to-female ratio of 4:1, especially in Western countries. Differences have been found in the role of gender influencing the severity of the disease. The latest data had identified better outcomes in females with HCL(2). In the last 40 years of HCL research a distinct gender participation gap has surfaced, favoring males in the enrollment of clinical trials. Our study aims to investigate the contributing factors to this imbalance, such as physio-pathological reasons, socio-demographic characteristics, accessibility barriers, and awareness limitations. Methods: In this descriptive, retrospective study, we searched EMBASE, PUBMED, and ClinicalTrials.gov from January 1983 to December of 2023 for publications on randomized clinical trials (RCT) in Hairy Cell Leukemia. The number of participants in clinical trials, their gender, the country where the trial was conducted, year of publication was recorded and descriptive statistical analysis of all the variables was performed. Results: We identified 57 studies comprising 4595 individuals with different subtypes of HCL. Of the total RCT, 79.10% of the patients were male and 20.89% were female. 49.12% of the studies were performed in the United States, 38.59% in Western Europe, 5.26% in Eastern Europe, and the remaining in Japan, Australia, and Iran. 36.84% of RCT were performed between 2000 and 2010. The male-to-female ratio was 7.92 for RTC performed between 1983 to 1989, 3.81 for RCT performed between 1991 to 1999 and 3.36 for RCT performed between 2000 and 2010. Conclusions: Female patients with HCL were recently shown to have a significantly longer progression free survival than male patients. Our retrospective analysis confirms that there is smaller than expected percentage of female participants enrolled in HCL clinical trials published over the last four decades. When examining the male-to-female ratio over different time periods there was a notable decrease from RCTs performed in the 1980s compared to RTCs performed after 2000. The gender disparity observed in clinical trials where males may be overrepresented could be attributed to the predominantly higher prevalence of both newly diagnosed and relapsed HCL in males, making them more likely to be eligible for the RCT. Bridging this gender gap in trials is crucial to accurately reflect the efficacy of novel therapies in both males and females, enabling improved treatment design and better outcomes for all.
Therapeutic utilization in chronic lymphocytic leukemia: A cross-sectional analysis of the Lymphoma Coalition’s 2022 Global Patient Survey.
Authors: Kalloger Steve , Watson Amanda , Sajkowski Shawn , Warwick Lorna 
Published: July 2024

e19026 Background: Chronic Lymphocytic Leukemia (CLL) is a highly prevalent disease with heterogenous prognostic trajectories. With a multitude of treatment options, we sought to explore therapeutic utilization trends from a global perspective in order to gain a more in-depth understanding of how different treatment regimens are utilized in different health systems. Methods: In 2022, The Lymphoma Coalition designed and globally deployed a survey to patients with lymphoma and CLL in order to gather patient reported outcomes and patient reported experience measures. Data were collected and enumerated with relevant contingency analyses performed to determine associations with a particular treatment regimen in the context of CLL. Results: The entire cohort of patients with CLL was 1289. The median age of the cohort was 65 and ranged from 26 to 97 years old. Biological sex was equally distributed with 50.5% of respondent indicating that they were female. Respondents were derived from 29 countries. The top three contributors to each region were China (50%), Australia (25%) and New Zealand (18%) for Asia-Pacific (N = 227); France (50%), Italy (13%) and Sweden (7%) for Europe (N = 950); Canada (75%) and The United States (25%) for North America (N = 112). Of those, 636 indicated that they received at least one therapy. The use of chemo-immunotherapy was most common (42%) followed by targeted therapy (32%), immunotherapy alone (18%), and chemotherapy alone (16%). Neither age nor biological sex was a significant predictor of therapy. Europe had the highest rates of chemo-immunotherapy utilization (45%) with North America and Asia-Pacific indicating 32% respectively (p = 0.01). Targeted therapy was used at a higher rate in North America (45%) but failed to demonstrate a significant difference against Asia-Pacific and Europe (31%); (p=0.10). Both immunotherapy and chemotherapy alone failed to demonstrate significant differences across regions. Conclusions: The data support that the majority of patients with CLL who require treatment are most likely to receive combination chemo-immunotherapy utilizing rituximab. However, we acknowledge that the data presented here is two years old and that the use of targeted molecular therapy is likely increasing. We found it reassuring that we could not identify any biases in the administration of the therapeutic regimens across the demographics of age and biological sex. Our research in this space will continue as we have deployed the 2024 version of the Global Patient Survey and have focused on increasing respondent participation from North America. With this new data, we plan on producing a time-dependent model to investigate how emerging therapies enter and expand in the CLL therapeutic space.
Real-world comparison of time to next treatment for patients with high-risk CLL/SLL in first line of treatment.
Authors: Hou Jing-Zhou , Li John , Vasudevan Anupama , Gart Mike , Choksi Rushir J. , Blanc Simon 
Published: July 2024

e19027 Background: The International Workshop on CLL recommends testing patients (pts) with CLL/SLL for deletion 17p (del17p) and tumor protein (TP) 53 mutations for prognosis and treatment decisions. Both Bruton Tyrosine Kinase inhibitors (BTKi) and B-cell lymphoma 2 protein inhibitor (BCL2i) are approved as effective frontline therapies for CLL/SLL pts, particularly those with high-risk features such as del17p and TP53. However, there is no clinical study directly comparing the efficacy of BTKi and BCL2i. We sought to understand the real-world use of BTKi and BCL2i as well as the differences in time to next treatment, a surrogate for progression-free survival, among CLL/SLL pts who were identified as having either del17p or TP53 mutations and treated with a BTKi or BCL2i in the 1L setting. Methods: We used the Integra Connect PrecisionQ real-world de-identified database of over 3 million cancer pts across 500 sites of care to identify CLL/SLL pts for the analysis. We observed pts who started 1L treatment between 3/4/2016 and 12/4/2023. Risk status was captured via medical chart curation to determine the presence del17p or TP53 mutations. Time to next treatment was measured from the treatment start to the first of the initiation of a subsequent line of therapy or death. Descriptive analyses were used and time to next treatment was analyzed using a Kaplan Meier analysis. Results: We identified 295 CLL/SLL pts with high-risk features. The median (IQR) age of these pts at treatment start was 74 (66,81) years old, 62% were male, 77% identified as White, 8% as African American, and 15% as Other. Of these high-risk pts, 72% had only a deletion 17p, 13% had only TP53 mutation, and 15% had both. The percent of high-risk pts who received a BTKi in 1L was 69% with a median (IQR) age of 75 (65, 81) at treatment start, while 13% received a BCL2i in 1L with a median (IQR) age of 70 (64,77) at treatment start. The percent of pts who received neither a BTKi or BCL2i in 1L was 18% with median (IQR) age of 74 (68,80) at treatment start. The median time to next treatment for those who received a BTKi was 68.4 months (95% Confidence Interval [CI]: 48.4, NA) compared to 45.5 months (CI: NA, NA) for pts who received a BCL2i. The median (IQR) duration for patients treated with a BCL2i +/- obinutuzumab was 396 (285,603) days. The probability of pts who did not initiate a next treatment at 30 months was found to be 71% (95% CI, 64% to 78%) for those who received a BTKi (p <0.05) compared to 92% (95% CI, 83% to 100%) for those who received a BCL2i. Conclusions: The real-world data comparison of 1L treatment in high-risk pts with CLL/SLL shows that, after 30 months, the probability of not initiating the next treatment is 92% for those treated with a BCL2i compared to 76% for those treated with a BTKi. Additional follow-up and a larger sample may be needed to further validate these findings.