bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between homologous recombination deficiency (HRD) gene mutations and the efficacy of venadaparib in combination with irinotecan as third- or fourth-line treatment in patients with metastatic gastric cancer (mGC).
Authors: Ryu Min-Hee , Kim Hyung-Don , Oh Do-Youn , Lee Keun-Wook , Rha Sun Young , Kim Seung Tae , Lee Won Sik , Hong Min Ju , Lee Myongjae , Roh Eun-Jihn , Ha Kyoung Soo
Published: July 2024

e16057

Background: Tumors with homologous recombination deficiency (HRD) have been suggested to be associated with a favorable response to poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitors. The aim of this exploratory analysis was to evaluate the association between the presence of HRD gene mutations and the efficacy of venadaparib, a novel PARP inhibitor, plus irinotecan in patients with mGC who had failed at least at least 2 lines of therapy. Methods: This was an exploratory analysis from a multi-national, phase 1b trial of venadaparib plus irinotecan in patients with mGC (NCT04725994). Tumor response was evaluated according to RECIST v. 1.1. Genomic analysis was conducted using ctDNA (GuardantOMNI Gene Panel version 1.0, Redwood City, CA) on Day 1 pre-dose. Results of the exploratory genomic analysis, which includes pathogenic or deleterious mutations of following genes: BRCA1/2, ATM, ATR, PALB2, RAD51, RAD51B/C/D, CHEK1/2, POLD1/2/3/4, BARD1, BRIP1, were analyzed with the efficacy outcomes. Results: In the dose-finding part of the clinical study, 26 patients were enrolled:13 had received two prior treatments and 13 had received three prior treatments, respectively. Of the 26 patients enrolled, 7 (26.9%) had mutations involved in HRD (4 with ATM, 1 with BRCA2, 1 with BARD1, and 1 with ATR mutations, respectively), and were treated with varying doses of venadaparib plus irinotecan. Among the 7 patients with a mutation in HRD genes, an objective response rate (ORR) was 57.1%, and median progression free survival (mPFS) was 5.6 months (95% confidence interval [CI] 1.2–not reached). For those without a mutation in HRD genes (n = 19), 1 patient achieved partial response and 13 achieved stable disease as best response with a mPFS of 4.0 (95% CI 2.9-5.5) months. Conclusions: Venadaparib in combination with irinotecan showed promising efficacy outcomes in patients with mGC, especially for those with mutations of HRD-related genes. Further development of this combination may consider a biomarker-based approach. Clinical trial information: NCT04725994 . [Table: see text]
Effectiveness and safety analysis of serplulimab-based regimens in patients with HER2-negative advanced gastric cancer from a real-world retrospective study.
Authors: Ding Qian , Wu Mengyao , Yu Danlei , Sun Di , Li Na , Tao Min , Zhu Hong
Published: July 2024

e16058

Background: Immune checkpoint inhibitors (ICIs) combined with chemotherapy are currently the preferred regimen for the treatment of HER-2 negative advanced gastric cancer. Serplulimab, an anti-PD-1 inhibitor, has been conditionally approved for the treatment of adult advanced gastric cancer. Because of the diverse nature of patients (pts), patient-centered, individualized treatment require accumulation of experience for real-world applications. Methods: We retrospectively studied 42 HER2-negative advanced gastric adenocarcinoma pts whose safety profiles of regimen containing serplulimab could be evaluated from April 2022 to October 2023 in the First Affiliated Hospital of Soochow University. Individualized treatment regimens mainly included serplulimab combined with one or two selected drug(s) from platinum, taxanes, and fluoropyrimidines. Results: Cut-off on January 30th, 2024, 30 pts (71.4%) received serplulimab based regimens as the first line (1L), 12 pts (28.6%) received the second or more line (≥2L) therapy. The characteristics were as follows: the median age, 66 years (range 35-80 years); male/female 33 (78.6%)/9(21.4%); ECOG performance status 0-1/38, ≥2/4. The median follow-up was 5.7 months (range 0.2-22.3 mos). A total of 227 cycles of treatment was administrated with a median of 4 cycles (range 1-17). Among the pts evaluable for RECIST 1.1, ORR and DCR were 42.9% and 69.0% respectively. There were 3 pts with 3 or more metastatic lesions achieved PR. Nine 1L pts and one 2L pt receiving serplulimab combined with dual chemotherapy containing platinum achieved disease control more than a year. We also tracked 11 pts who experienced grade 1-2 immune-related adverse events (irAEs) reaped over 6 months PFS. Two of four pts who stopped immunotherapy but maintained 1 or 2 cycles of original combined chemotherapy obtained PFS for more than a year. Median PFS and DoR have not reached. The most common grade 3/4 AEs was myelosuppression (7.1%), increased aminotransferases (4.7%) and elevated creatinine (2.3%). 15 (35.7%) pts experienced immune-related adverse events (irAEs) of any grade including aminotransferase elevation, increased creatinine, but no grade 3 or higher irAEs observed. Conclusions: The real-world data analysis shows that serplulimab-based flexibly combination according to patient status, achieving tumor control in diverse pts while ensuring drug safety. We successfully validated the effectiveness and safety of chemo-immunotherapy strategy in real-world practice. [Table: see text]
Efficacy, safety and DNA methylation analysis of cadonilimab combined with taxane and cisplatin as the first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC): An open-label, multicenter phase II trial– Updated results from AK104-IIT-014.
Authors: Qu Wang , Gao Jing , Zhang Bo , Liu Yun , Guo Yijia , Yang Mudan , Huang Jing
Published: July 2024

e16064

Background: Immune checkpoint inhibitors combined with chemotherapy has become the current first-line standard treatment for advanced ESCC, while still having a lot of room for improvements in objective responses and survival. Cadonilimab, a bispecific antibody simultaneously targeting PD-1 and CTLA-4, may further boost anti-tumour activity with a satisfied safety profile. Here, we present the updated data for the safety and efficacy of Cadonilimab combination therapy as the first-line treatment in advanced ESCC. Methods: Treatment-naïve patients (pts) with unresectable locally advanced or metastatic ESCC were eligible for inclusion. Cadonilimab (10mg/kg, iv, d1, q3w) combined with paclitaxel or nab-paclitaxel (175 mg/m2, iv, d1, q3w) and cisplatin (65 to 75 mg/m2, iv, d1, q3w) were administrated for up to 6 cycles, then Cadonilimab (10mg/kg, iv, d1, q3w) monotherapy continued as maintenance until progressive disease or unacceptable toxicity, with a maximum of 24 months. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Plasma cell-free DNA samples were collected before and after treatment and prepared for DNA methylation level sequencing. Results: At updated analysis (cut-off: February 5, 2024), 35 pts were enrolled with a median age of 61 years (range 44-75), 82.9% were male, 57.1% had PD-L1 CPS<10 and 88.6% had distant metastases. In the efficacy-evaluable population (n = 29), 5 pts reached complete response (CR), 21 pts had partial response (PR) and 3 pts had stable disease (SD). The ORR was 89.7% (95%Cl: 71.5%-97.3%) and the DCR was 100.0% (95%Cl: 85.4%-100.0%). Among evaluable pts with PD-L1 CPS≥10 and PD-L1 CPS<10, the ORR were 100.0% (12/12) and 81.3% (13/16), respectively. SEPT9 methylation was significantly higher in patients with CR or PR compared to patients with SD (33.28% vs 3.87%, p < 0.001). The median PFS and OS was still not reached. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 9 (25.7%) pts. The most common TRAEs were neutropenia (17.1%), leukopenia (5.7%) and hyponatremia (5.7%). Immune-related adverse events were observed in 9 pts (25.7%). Three pts (8.6%) suffered from serious adverse events, and no grade 5 TRAEs or death were observed. Conclusions: The updated results suggested that bispecific antibody AK104 combined with taxane and cisplatin as first-line treatment showed promising anti-tumor activity and manageable safety in patients with advanced ESCC. DNA methylation level might be a potential biomarker for guiding patient outcomes. Follow-up is ongoing for survival analysis. Clinical trial information: NCT05522894 .
The clinical significance of PRMT8 expression in esophageal squamous cell carcinoma and the influence on prognosis.
Authors: Liu Sihan , Zuo Jing , Zhang Xue
Published: July 2024

e16066

Background: Protein arginine methyltransferase 8 (PRMT8), a member of protein arginine methyltransferases, is an enzyme catalyzing the methylation of arginine residuals of histones and non-histone proteins to serve as one of many critical post-translational modications (PTMs). Esophageal squamous cell carcinoma (ESCC) is the third most common cancer type of the gastrointestinal tract with poor prognosis. Abnormal arginine methylation modifications are closely associated with the development of ESCC and can exert oncogenic effects by regulating a variety of cellular processes. However, the expression of PRMT8 in ESCC and its influence on prognosis is currently unknown. Methods: After passing the application and obtaining the approval of the hospital ethics review committee and obtaining the informed consent of all patients and their families, we collected 46 cases of renal cell carcinoma diagnosed in the Fourth Hospital of Hebei Medical University from 2018 to 2023, and postoperative pathological reports of all patients confirmed to be ESCC. We followed the selected patients and obtained complete data. All the pathological specimens of the selected patients were resectioned and then subjected to immunohistochemical examination to observe the expression differences of PRMT8 in ESCC, and parallel semi-quantitative analysis. Finally, the data of the patients were statistically built. Results: PRMT8 is mainly stained on the plasma membrane of tumor cells. The difference in expression levels between ESCC and normal tissue adjacent to the cancer was statistically significant (P < 0.01). This study found that the patient’s gender, age, tumor side have no correlation with the expression levels of PRMT8 (P > 0.05), while the three indicators of tumor size, TNM stage, and lymph node metastasis are positively correlated with the expression levels of PRMT8 and the difference is statistically significant (P < 0.01). Moreover, the positive staining of PRMT1 in ESCC was significantly correlated with poor prognosis of ESCC patients. Conclusions: The expression of PRMT8 is highly expressed in ESCC and associated with aberrant clinicopathological characteristics and poor prognosis. PRMT8 is a potential target for the stratification and treatment of ESCC.
Concordance of PD-L1 combined positive score (CPS) analysis between primary gastric cancer and matched peritoneal metastasis.
Authors: Massa Valentina , Salani Francesca , Grelli Giada , Genovesi Virginia , Vivaldi Caterina , Signorini Francesca , Ugolini Clara , Filice Maria Elena , Bernardini Laura , Cesario Silvia , Caccese Miriam , Graziani Jessica , Bartalini Linda , Berra Dario , Mangogna Francesco , Nardini Vincenzo , Masi Gianluca , Fornaro Lorenzo
Published: July 2024

e16068

Background: Peritoneum represents one of the most common metastatic sites of gastroesophageal adenocarcinoma (GEA) and is associated with poor prognosis. Programmed death-ligand 1 (PD-L1) expression is a recognized predictive biomarker of response to immune checkpoint inhibitors (ICIs) in the first-line setting. However, data from pivotal trials showed poorer clinical efficacy of ICIs in the sub-set of patients with peritoneal involvement, regardless of PD-L1 score magnitude. Here, we investigated the temporal and spatial heterogeneity of PD-L1 expression between primary tumor and matched peritoneal metastasis. Methods: PD-L1 expression according to CPS was determined by immunohistochemistry using VENTANA PD-L1 (SP263) assays on formalin-fixed paraffin-embedded (FFPE) tumor tissues derived from 22 patients treated at our institution for advanced GEA from September 2015 to August 2023. Concordance rate of PD-L1 expression between primary tumor and matched peritoneal metastasis using PD-L1 CPS cut-off of 1 and 5 was reported (spatial heterogeneity); additionally, concordance between PD-L1 value before and after the administration of systemic treatments was analyzed (temporal heterogeneity). Results: 12(54.5%)/5(22.7%) primary tumor samples and 12(54.5%)/1(4.5%) peritoneal metastases showed PD-L1 CPS ≥ 1/ ≥ 5, respectively. Concordance of PD-L1 CPS between primary and peritoneal specimens was 54.5% and 72.7% according to CPS cuts-off of 1 and 5, respectively, highlighting marked spatial heterogeneity. High concordance rate (94%) was reported between negative PD-L1 CPS primary tumor samples and matched peritoneal metastases, against the cut-off of CPS ≥ 5; in contrast, none of the positive primary tumor samples retained PD-L1 expression in the peritoneum. Evident temporal heterogeneity of PD-L1 expression was also observed, with 56% concordance against CPS ≥ 5 in the pre- versus post-treatment comparison. Conclusions: PD-L1 expression in GEA is characterized by spatial and temporal heterogeneity which is more prominent for lower CPS cut-offs values. This evidence could hamper its role as predictive biomarker for ICIs. The high intra-patient discordance rate of PD-L1 CPS expression between positive primary tumor samples and matched peritoneal metastases suggests that peritoneal specimens should not be recommended as the preferred source for PD-L1 assessment.
Life expectancy of patients with early gastric cancer who underwent curative gastrectomy: Comparison with the general population using the Korean Statistical Information Service database.
Authors: Ko ChangSeok
Published: July 2024

e16077

Background: Although clinical trials have reported the long-term survival of patients with early gastric cancer, data comparing their life expectancy with that of the general population is scarce. Our study estimated these patients’ life expectancy and analyzed the differences in life expectancy between patients with early gastric cancer and the general population. Methods: We enrolled patients who underwent curative gastrectomy and were diagnosed with pathologic stage 1 gastric cancer at Asan Medical Center from the gastric cancer registry. We determined patients’ survival status through the national health insurance system. Their life expectancy was analyzed and compared with that of the general population, utilizing data from the Korean Statistical Information Service database. Results: This cohort comprised 8,637 patients and 64.7% were men. Approximately 17.3% of participants were aged 70 years and older. Approximately 20% of patients underwent total gastrectomy. Life expectancy was favorable among women. Across all age groups, women’s life expectancy generally exceeded 80 years. Male patients showed a reduced life expectancy, typically 4-10 years shorter than their female counterparts. The average life expectancy of male patients aged over 80 years who underwent total gastrectomy was about 5 years, whereas that of their female counterparts was approximately 7 years. Female patients undergoing distal gastrectomy did not demonstrate a statistically significant variance in life expectancy compared to the general population. Conclusions: This study provided comprehensive life expectancy data, organized by age, sex, and type of gastrectomy in a large stage 1 gastric cancer cohort. Elderly patients undergoing total gastrectomy with limited life expectancy may benefit from considering alternative treatment options instead of total gastrectomy.
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.
Relapse Hodgkin lymphoma autologous stem cell transplant long term follow up.
Authors: Abedrabo Sabree
Published: July 2024

e19031

Background: Autologous Stem Cell Transplantation (ABMT) is a standard treatment approach for patients with relapsed Hodgkin’s Lymphoma (HL). We wish to report long term (>10 year) outcomes for patient’s with HL treated with ABMT at our institution. Methods: We treated 35 patients over a 30 year time period (1992-2022). Of these 35 patients, there were 19 males and 16 females with a median age of 41 years (range 21-70 years) and a median performance status of 1 (0-1). The preparative regimen was carmustine, etoposide, and melphalam (CEM, 1992-2005) and BCNU, etoposide, cytarabine and melphalan (BEAM, 2006 to present). Bretuximab was added to BEAM in 2018 as post-transplant consolidation therapy in 13 patients. All patients underwent mobilized peripheral blood stem collections with high dose filgrastim, and starting in 2008 were mobilized with both filgrastim and plexiform. The required stem cell product was at a minimum of 2 million CD34+ cells per kilogram of body weight. Results: Fifteen patients received CEEM and 9/15 (60%) achieved a complete response (CR). Twenty patients received BEAM and 16/20 (80%) achieved a CR, p=0.27 (Fisher’s exact test). The median time to hematological recovery was 12 days (range 8-21). Treatment related complications included: S. epidermis sepsis (3 patients), E. coli sepsis (3 patients), and esophageal perforation that lead to death in 1 patient. With a median follow up 13 years (range 1-23 years), the actual 10 year disease free survival (DFS) is 52% and overall survival (OS) is 64%. The actuarial DFS and OS at 15 years are 52% and 64% respectively. Six patients are in continuous CR for greater than 20 years. Long term complications at greater than 15 years include: cardiomyopathy (5 patients), breast cancer (1 patient), and liposarcoma (1 patient). Conclusions: Patients with relapsed HL can achieve long term curative outcomes when treated with ABMT with most frequent long term complication being cardiomyopathy.
Effects and outcomes of tumor lysis syndrome in patients admitted with Hodgkin and non-Hodgkin lymphoma: A National Inpatient Sample study (2019-2020).
Authors: Gaddam Mrunanjali , Iqbal Rabia , Jayakumar Jayalekshmi , Ginjupalli Manasa , Vachhani Bhavyakumar , Sanka Sujana , Thanneeru Priya , Sekandlapuram Rohit , Sanghvi Ankushi , Hotwani Priya , Nanavaty Dhairya , Kumar Vikash , Singh Surbhi , Colon Ramos Ana , Clement Jincy
Published: July 2024

e19032

Background: Tumor Lysis Syndrome (TLS) is a life-threatening oncologic emergency. The newer advancement in therapeutic approaches in oncology has widened the range of malignancies associated with TLS. A lot of literature on the incidence of TLS in various solid malignancies exists. However, the effects of TLS on hematological malignancies, especially Hodgkin’s Lymphoma (HL) and Non-Hodgkin’s Lymphoma (NHL) have rarely been analyzed. Our study aims to identify the impact of TLS in patients hospitalized with HL and NHL and draw a comparison between HL and NHL. Methods: We analyzed the National Inpatient Sample database from 2019 - 2020 to identify patients > 18 years old with a primary diagnosis of HL and NHL. We compared the TLS prevalence and all-cause in-hospital mortality, length of hospital stay (LOS), and total costs in patients admitted with HL and compared it with NHL. Categorical variables were compared using the chi-square test, and the t-test compared continuous variables. Multivariable regression analyses were performed adjusting for demographics, hospital-level characteristics, and relevant comorbidities. Results: Among 24,550 Hodgkin’s Lymphoma (HL) hospitalizations and 108,060 Non-Hodgkin’s Lymphoma (NHL) hospitalizations, TLS was diagnosed in 0.69% of HL patients and 0.89% of NHL patients. In-hospital mortality was significantly higher in both HL (44.1%) and NHL (28.3%) patients with TLS compared to those without TLS (HL: 4.5%, NHL: 5.1%). Multivariate regression analysis revealed that TLS presence increased the chance of mortality among both HL (OR 17.9) and NHL (OR 7.3) patients. TLS also significantly impacted secondary outcomes including Acute Kidney Injury (AKI) and Hyperkalemia in both HL and NHL patients. No statistically significant differences were found in the odds of cardiac arrhythmias between HL and NHL patients with TLS (Table). TLS was associated with longer Length of Stay and higher total hospital costs in both HL and NHL patients compared to those without TLS. Conclusions: TLS is significantly associated with increased mortality in patients with HL and NHL, more in HL compared to NHL. In patients with HL, and NHL, TLS is an independent risk factor for in-patient mortality, the longer LOS, and the total cost, thereby incurring an increased burden on healthcare resources. Our study aims to highlight the need for greater vigilance in this vulnerable group when TLS occurs. [Table: see text]
Real-world adherence and healthcare resource utilization of Bruton tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma.
Authors: Shah Bijal D. , Furnback Wesley , Esselman Kaitlyn , Chuang Po-Ya , Xue Mei , Yang Keri
Published: July 2024

e19048

Background: This study aimed to examine treatment adherence and healthcare resource utilization (HCRU) of BTKi treatment in mantle cell lymphoma (MCL). Methods: The Symphony Integrated Dataverse (IDV) was used to conduct a retrospective observational study. Adult patients with MCL initiating their first BTKi or second BTKi (after ibrutinib) between 01/2020 and 10/2023 were included in the study. The index was defined as the date of BTKi initiation. Patients without 30 days of continuous enrollment pre- and post-index date were excluded. Patients were followed until the end of the study period or lost to follow-up. Adherence was evaluated by compliance and persistence. Compliance was calculated as the proportion of days covered >0.80 using 30-day intervals from initiation to 1 year. Persistence was measured as the proportion of patients who remained in treatment among patients with sufficient follow-up periods. HCRU was measured by all-cause outpatient visits, inpatient services, and other medical/hospital services per-patient-per-month (PPPM) during BTKi treatment. Results: Among 2,122 patients who were first-time BTKi users, there were significant differences for mean age at index (acalabrutinib=70; ibrutinib=68; zanubrutinib=70, P<.0001), commercial insurance (acalabrutinib=34%; ibrutinib=42%; zanubrutinib=47%, P<.0001), and baseline atrial fibrillation (acalabrutinib=1.94%; ibrutinib=1.24%; zanubrutinib=3.47%, P=0.0232). A total of 228 patients switched from ibrutinib to acalabrutinib or zanubrutinib. Adherence results suggested zanubrutinib had numerically better 1-year compliance ( P=0.2176) and treatment persistence at 1 and 2 years ( P=0.2687; P=0.6270) for patients who switched from ibrutinib to zanubrutinib or acalabrutinib (Table). HCRU showed that the mean (SD) outpatient visits (1.12 [1.67] vs 1.62 [3.17]; P=0.1755) and inpatient services (0.22 [0.68] vs 0.68 [3.12]; P=0.1693) were lower in patients switched from ibrutinib to zanubrutinib than acalabrutinib. Conclusions: In this study, zanubrutinib was associated with a trend towards improved compliance, persistence, and HCRU when used as the first BTKi and after prior ibrutinib. [Table: see text]