bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enrichment of somatic mosaic states involving DNA damage response and repair genes in patients treated with 177Lutetium.
Authors: Kusne Yael , Mosalem Osama M , Lasho Terra L. , Pritzl Stephanie L , Finke Christy , Hobday Timothy J. , Starr Jason S. , Bekaii-Saab Tanios S. , Halfdanarson Thorvardur Ragnar , Sonbol Mohamad B. , Orme Jacob , Childs Daniel S , Sartor Oliver , Patnaik Mrinal 
Published: July 2024

3020 Background: Radioligand therapy (RLT) use has been increasing with the approval of 177Lu-Dotatate for metastatic neuroendocrine tumors (NET) & 177Lu-PSMA-617 for metastatic castration resistant prostate cancer (mCRPC). Therapy-related myeloid neoplasms [tMN, including myelodysplastic syndrome (MDS) & acute myeloid leukemia, (AML)] have been reported after 177Lutetium (177Lu) for NET with rates of 2-20% & median time from first 177Lu to tMN of 2.8yrs [4-12]. Clonal hematopoiesis (CH) is a risk factor for tMN, with the spectrum of CH depending on selection pressures. To describe the prevalence of therapy selected CH & tMN, we performed a retrospective analysis of patients (pts) who had a bone marrow biopsy (BMB) post-177Lu. Methods: After IRB approval, we queried the electronic health record for pts with BMB post-177Lu. Pt demographics, treatment history, labs & BMB results were collected. Results: Fifty-seven pts met criteria, 41 (72%) with NET & 16 (28%) with mCRPC. . Median age at BMB was 68yrs (range, 28-85). Of the 57pts, prior treatments included: radiation (RT) in 21 (37%), temozolomide in 14 (25%), taxane in 15 (26%), & platinum agents in 10 (18%). The median number of 177Lu cycles was 4 (range, 1-11).Cytogenetics were available in 84% (n = 48) & were normal in 60% (n = 29). Of those with abnormal cytogenetics (n = 18, 38%), the most common abnormalities involved chromosome (chr) 7 (n = 12, 26%), chr 5 (n = 7, 15%), chr 20 (n = 5, 11%) and complex karyotypes in 7 (15%), with 3 (17%) of these patients having no mutations. Diagnoses were assessable in 49 (86%) pts: 15 (31%) with undefined cytopeniasand 16 (33%) with tMDS. Metastatic carcinoma was identified in 17 Fifty-one percent (n = 29), at a median of 0.5yrs (range, 0.04-2.6) after hematologic diagnosis. Conclusions: The enrichment of CH involving the DDR pathway in recipients of 177Lu underscores the impact of RLT on bone marrow progenitors.
Multicentric retrospective study on the treatment characteristics, efficacy and safety of eribulin in Slovenian patients with breast cancer.
Authors: Dobovisek Luka , Borstnar Simona , Ravnik Maja , Privsek Nina 
Published: July 2024

e13123 Background: Eribulin mesylate (eribulin) is a microtubule inhibitor and a synthetic analog of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Eribulin was approved based on the randomized Phase 3 EMBRACE clinical trial, which showed an improvement in survival compared to chemotherapy (CT) of the physician's choice. The efficacy and safety of eribulin treatment in real-world settings has been reported in several studies: Korean and Chinese multicenter retrospective studies and a meta-analysis from 2020. Methods: We included all patients treated with eribulin between January 24, 2013 and September 14, 2022 at the Institute of Oncology Ljubljana (85.4% of patients) and University Medical Centre Maribor (14.6%). Clinical data were collected retrospectively from paper and electronic patient records. The primary endpoints were median progression-free survival (PFS), overall survival (OS), response rates and safety. We performed a descriptive statistical analysis and a survival analysis using the Kaplan-Meier method. Results: 205 patients, whose average age was 58.6 (29-88) years, were included in the study. The majority (79%) had a hormone receptor (HR+) positive tumor, 12.2% were HER2 positive and 16.6% were triple negative. 32/205 (15.6%) were primary metastatic. Of the remaining 173 patients, 160/173 (92.4%) received adjuvant therapy, of which 15% received hormone therapy, 23.1% received CT and 61.9% received both. At the start of treatment with eribulin, 84.9% had visceral tumors and 14.6% had tumors in the CNS. The median number of all treatment lines was 6 (range 2–15) and the median number of CT lines was 4 (0–13). The ECOG performance status was: 0 in 4.9%, 1 in 53.2%, 2 in 35.1% and 3 in 4.9% and 4 in 0.5% of patients. The objective response rate was 7.3% and clinical benefit was achieved in 27.3%. The median CT line in which eribulin was used was the fourth (1–10). Eribulin was used as the last CT line in half of the patients. The median PFS was 3.01 months (95% confidence interval 2.56–3.47) and the median OS was 6.68 months (95% confidence interval 5.60–7.77). Patients who received eribulin in the first 3 lines of treatment had a better OS than those who received eribulin in later lines. Adverse events (AEs) occurred in 52.7%. Eribulin therapy was discontinued due to AEs in 18.5% of patients. The most common AE was fatigue (25.9%), followed by neuropathy and neutropenia (22.9% and 18%). Conclusions: In our retrospective analysis, we found significantly worse results of treatment with eribulin than in previous studies. In our population, eribulin was used in the late stages of treatment and in older patients with poorer performance status. The proportion of patients with visceral and CNS tumors was higher. The side effects were comparable.
First-line TQB2450 plus anlotinib combined with paclitaxel and cisplatin for advanced esophageal squamous cell carcinoma (ESCC): Update results of a multicenter phase II trial.
Authors: Wang Junsheng , Li Ning , Guo Yanzhen , Cheng Yufeng , Li Baosheng , Luo Suxia 
Published: July 2024

e16011 Background: PD-1 inhibitor combined with chemotherapy are the standard first-line treatment for advanced ESCC. Anlotinib, a multitargeted tyrosine kinase inhibitor (TKI), has been demonstrated favorable efficacy and manageable toxicity as both first-line treatment when combined with TP and second-line monotherapy in advanced ESCC. TQB2450 is a novel humanized anti-PD-L1 monoclonal antibody. We conducted a phase II trial to evaluate the efficacy and safety of alotinib combined with TQB2450, cisplatin, and paclitaxel as first-line treatment for advanced ESCC. Here is the update results. Methods: Eligible patients (pts) with previously untreated unresectable locally advanced or metastatic ESCC received TQB2450 (1200mg, iv, d1, q3w) plus anlotinib (10mg, po, d1~14, q3w) combined with paclitaxel (135mg/m2, iv, d1, q3w) and cisplatin (60~75mg/m2, iv, d1~3, q3w) for 4 - 6 cycles as initial therapy. Patients without progressive disease (PD) continued to receive same dose of anlotinib plus TQB2450 as maintenance therapy until PD or unacceptable toxicity. The primary endpoint was PFS (RECIST version 1.1). Secondary endpoints included iPFS (iRECIST), ORR (RECIST version 1.1), DCR, DOR and safety. Results: At the data cutoff date of November 14, 2023, 50 pts were enrolled with a median age of 64 years (range 41-74), male (39/50, 78%) and ECOG PS 1 (38/50, 76%). Among 43 tumor response evaluable pts , 4 achieved complete response, 32 had partial response and 8 had stable disease. The ORR was 72.00% (95% CI: 57.51, 83.77) and the DCR was 84.0% (95% CI: 70.89, 92.83). The 12-month PFS rate was 66.84% (95% CI: 48.73, 79.79) and the 12-month OS rate was 74.22% (95% CI: 59.06, 84.46), but the median PFS and OS was not reached. The incidence of ≥G3 treatment emergent adverse events was 78%, mainly included neutropenia (44%, 22/50), leukopenia (24%, 12/50) and hypertension (20%, 10/50). 20 pts (48%, 24/50) occurred serious AEs. Conclusions: The combination of TQB2450 plus anlotinib, paclitaxel and cisplatin, demonstrated encouraging efficacy and manageable toxicity in patients with advanced ESCC when used as first-line treatment. Clinical trial information: NCT05013697 .
Intratumoral and fecal microbiota to reveal microbial markers associated with gastric carcinogenesis.
Authors: Wang Yiwen , Han Wenjie , Wang Yue , Sun Tao , Xu Junnan , Han Li , Liu Xiaolin 
Published: July 2024

e16014 Background: The relationship between dysbiosis of the gastrointestinal microbiota and gastric cancer (GC) has been extensively studied. However, microbiota alterations in GC patients vary widely across studies, and there are still no diagnostic biomarkers for early GC that can be replicated in multiple populations. Therefore, this study aimed to characterize the gastrointestinal microbial communities associated with gastric carcinogenesis. The diversity results showed significant differences in GC patients' intratumoral microbiota compared with the non-GC population. Methods: 1,642 gastric tissue samples and 394 fecal samples were tested using 16s rRNA amplicon sequencing. After identifying taxa with differential biomarkers, we built a random forest model to distinguish gastric cancer from normal controls. We validated the generalizability and specificity of the model using an external cohort. In addition, we used the KEGG database for predictive analysis of colony correlation functions. Results: The positive correlation between GC-enriched bacteria increased, and the positive correlation between GC-depleted bacteria decreased compared to healthy individuals. Functional analysis revealed that carbohydrate and iron metabolism pathways significantly enriched in the GC phase. In addition, we explored non- Helicobacter pylori ( HP) commensals, which play an essential role in HP-negative and HP-positive GC. Finally, random forest models were constructed using the specific taxa associated with GC obtained from the Lefse analysis, and it was found that the combination of Lactobacillus and Streptococcus included alone could well discriminate between GC patients and healthy individuals in fecal samples (area under the curve (AUC) = 0.7949). We also validated it in an independent cohort (AUC = 0.7712). Conclusions: This study demonstrates the validity of GC-specific microbial markers across multiple populations, which may contribute to early non-invasive diagnosis of GC.
Triple combination treatment of trastuzumab, chemotherapy and immune checkpoint inhibitor in HER2 positive unresectable, locally advanced, metastatic gastric and esophageal adenocarcinoma: A systematic review and meta-analysis.
Authors: Revillas Lorenz Fort Estrada , Dy Carlos , Lalusis John Kelvin 
Published: July 2024

e16071 Background: The current standard of care for unresectable, locally advanced or metastatic HER2 positive gastric, esophageal and gastroesophageal junction adenocarcinomas is the combination of the anti HER 2 antibody trastuzumab and cytotoxic chemotherapy. In recent years, the addition of immune checkpoint inhibitors to this combination has been studied to determine if it can improve clinical outcomes for this disease. This systematic review and meta-analysis evaluated high-quality data from clinical trials to determine the role and efficacy of this triple combination treatment. Methods: A systematic search of English-language articles on PubMed, Cochrane and Google scholar was done to identify randomized trials (RCTs) investigating the use of triple combination treatment of anti-Her 2 antibody, chemotherapy and immune checkpoint inhibitor in the treatment of unresectable, locally advanced, or metastatic HER2 overexpression positive gastric, esophageal and gastroesophageal junction adenocarcinoma. Quality of the studies was assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Inverse variance was the statistical method used with random effects as the analysis model in the production of the Forest plot and calculation of risk ratio (RR) at 95% confidence intervals (CI). Results: Four (4) RCTs (N = 866) were included for quality assessment and data extraction. Two (2) of these RCTs (N = 80) were single arm studies which both showed favorable outcomes in terms of objective response rate and progression free survival. The two (2) other RCTS (N = 786), each had two arms (triple regimen versus comparator) and were used in the meta-analysis. Risk of bias was low and heterogeneity was low (I2 below 50%). Pooled results showed that in patients given triple combination regimen, there is statistically significant improvement in progression free survival (RR 1.55 95% CI 1.20-2.00, p 0.0007). There is also an increase in overall response rate in favor of the triple combination regimen, albeit not statistically significant (RR 1.31 95% CI 0.99-1.74, p = 0.06). Conclusions: The addition of an immune checkpoint inhibitor to the current standard of care of anti Her 2 antibody and chemotherapy provides meaningful results in terms of tumor response and progression free survival in Her 2 positive locally advanced or metastatic gastric and esophageal adenocarcinomas. More robust trials, and data on overall survival supporting the use of this triple regimen may help re-shape the current standard of care for this disease.
Combining nimotuzumab with PD-L1 inhibitors and chemotherapy to treat esophageal cancer: A retrospective study.
Authors: Chen Size , Lin Yiguang , Dong Jiayi , Song Minghan , Lijuan Shao 
Published: July 2024

e16072 Background: Combining immunotherapy with targeted therapy and/or chemotherapy has been shown to have superior clinical benefits in cancer treatment. The combination of immunotherapy, targeted therapy, and chemotherapy may be an option for esophageal cancer. This study assessed retrospectively the efficacy and safety of nimotuzumab combined with the PD-L 1 inhibitor and chemotherapy in the treatment of patients with esophageal cancer. Methods: All enrolled patients were from the First Affiliated Hospital of Guangdong Pharmaceutical University between September 2021 and August 2023. All patients received intravenous nimotuzumab (200 mg/w) combining with PD-L1 inhibitors (Tirelizumab; Caralizumab; Sintilimab; Pembrolizumab; Nivolumab and Penpulimab, 6 cycles in total) and chemotherapy (albumin paclitaxel 150mg/m2, cisplatin 25mg/m2, for 1-3 days per cycle, for a total of 6 cycles). The primary endpoint was overall survival (OS). Secondary endpoints consisted of the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety. Efficacy was assessed according to the criteria of RECIST 1.1 and while adverse events (AEs) were graded according to CTCAE 5.0. Following treatment, patients’ general condition, levels of lymphocytes, IL-6, hs-CRP, PCT, CYFRA21, NSE(E), and SCC were monitored regularly. Results: A total of18 patients diagnosed with EC were enrolled in the study. The majority of the patients were male (16/18), 17 (94.4%) patients diagnosed with esophageal squamous cell carcinoma. Lymphatic metastasis occurred in 13 (72.2%) patients and 5 (27.8%) patients experienced distant metastases. Six (33.3%) patients received radical surgery and five (27.8%) patients did not receive systematic antitumor therapy in the past. 17 (94.4%) patients diagnosed with esophageal squamous cell carcinoma (ESCC). No patient achieved complete response (CR) and 6 (33.3%) patients achieved partial response (PR). The ORR and DCR were 33.3% and 83.3%, respectively. The median OS was not achieved, the 12-month OS rate was 84.8%, 24-month OS rate was 74.2%. The median PFS was 7.9 months, the 12- and 24-month PFS rates were 44.0% and 36.7%, respectively. The incidence of Grade ≥ 3 AEs was 43.85%, including anemia (18.8%), lymphopenia (18.8%) and rash (6.3%). Conclusions: This combinational treatment regimen results in a significant improvement in OS compared to the combination of PD-L1 inhibitors and chemotherapy without increased AEs. Compared to other combinations of targeted drugs with PD-L1 inhibitors and chemotherapy, the use of nituzumab significantly prolonged mPFS and increased OS rates at 12 and 24 months.
Phase 2 study of concurrent cisplatin, capecitabine and celecoxib with radiotherapy in patients with carcinoma of the oesophagus.
Authors: Srivastava Kirti , Khalid Bushra , Tuteja Jasmeet Singh , Verma Mranalini , Bhatt Madan Lal Brahma 
Published: July 2024

e16078 Background: Oesophageal cancer is the fourth common cause of cancer-related deaths in India. Definitive Chemoradiotherapy is standard for non-metastatic Squamous cell carcinoma of the oesophagus cancer. Chemoradiotherapy when given as definitive treatment is more effective than radiotherapy or chemotherapy alone. This treatment is usually offered to patients who are unsuitable for surgery. Unsuitability for surgery might be due to the extent of disease precluding the likelihood of a curative resection, or because the patient is physiologically not fit for surgery because of comorbidities or poor performance status. The aim of the present study was to analyse the effect of definitive concurrent chemo-radiotherapy in oesophageal cancer patients and assessment of toxicity profile and response. Methods: In the present Phase II study total 22 patients were recruited who had non-metastatic histologically confirmed carcinoma of the oesophagus selected for definitive chemoradiotherapy were enrolled. Chemotherapy consisted of three-weekly cycles of Inj. Cisplatin 60 mg/m2 given on D1, Tab. Capecitabine 625 mg/m2 given BD on D1-D21, and Tab. Celecoxib 200mg given BD on D1-D21. The planned protocol involved four cycles of concurrent chemotherapy. Radiotherapy in a dose of 50.4 Gy in 28 fractions was initiated on D1 of the second cycle of concurrent chemotherapy, or latest by D1 of the third cycle of concurrent chemotherapy. Results: In this Phase 2 study, 22 patients with a mean age of 55.68 ± 11.23 years, were treated. The tumor length averaged 6 ± 2.25 cm, with most common Stage III (52.17%), followed by Stage II (34.78%), Stage I (8.69%), and Stage IVA (4.34%). Grade 3 dysphagia was predominant (56.52%), followed by Grade 2 (34.78%), Grade 1 (4.35%), and Grade 4 (4.35%). During treatment, notable grade 1-2 toxicities included esophagitis(68%), fatigue(63%), nausea (54%), neutropenia (31%), anemia (22%), mucositis(18%), diarrhoea(13%), dermatitis(9%). There was gradual decline in the severity of dysphagia of all patients. Of the 8 patients evaluated for response with a median follow up of 12 months, the complete response rate was 25%, partial response rate was 25% and 37.5% showed stable disease whereas 12.5% developed progressive disease. The median overall survival is yet to be estimated. Conclusions: A notable clinical response, indicating a substantial treatment effect was observed. While some treatment-related toxicities were present, This approach shows potential in the treatment of oesophageal carcinoma. However, this study is still ongoing and it would be hasty to draw definitive conclusions.
Real-world treatment switching and sequencing to next line of therapy of zanubrutinib, acalabrutinib, and ibrutinib in CLL/SLL.
Authors: Pinilla-Ibarz Javier , Xue Mei , Wu Elizabeth , Esselman Kaitlyn , Furnback Wesley , Challagulla Swetha , Yang Keri 
Published: July 2024

e19022 Background: Evaluating use of Bruton tyrosine kinase inhibitors (BTKis) for the treatment of CLL/SLL is crucial to understand real-world outcomes of these therapies in diverse populations. The objective of this study was to evaluate real-world switching and sequencing to next line of therapy in patients (pts) initiating BTKis as first-line (1L) or second-line (2L) CLL/SLL treatment. Methods: A retrospective study was conducted using IntegraConnect PrecisionQ to identify adult pts with ≥1 diagnosis for CLL/SLL initiating zanubrutinib (zanu), acalabrutinib (acala), or ibrutinib (ibru) in 1L or 2L between 1/1/2020-2/28/2023 (index period). Index date was defined as date of BTKi initiation. Pts were required to be continuously enrolled for ≥30 days pre- and post-index date. Treatment switching was measured as pts initiating another treatment within same line or advancing to next line of therapy within 90 days. Sequencing to next line of therapy was calculated from time to next treatment Kaplan-Meier curve, censoring patients at end of follow-up, and reported as proportion of pts receiving next line of therapy at 180 days. Results: 2,816 pts initiated a 1L BTKi (zanu=157; acala=1,238; ibru=1,421) and 1,253 initiated a 2L BTKi (zanu=107; acala=672; ibru=474). No major differences were observed in baseline demographic and clinical characteristics among 1L and 2L BTKi cohorts. Median follow-up in 1L was 123 days for zanu, 406 days for acala, and 637 days for ibru. Regardless of line of therapy, switching rate at ≤60 days and 61-89 days was statistically significantly lower for pts receiving zanu vs acala and ibru (P<0.0001, both 1L and 2L) (Table). Proportion of pts receiving next line of therapy at 180 days was lower for zanu vs acala and ibru (1L P=0.2958; 2L P<0.0001) (Table). Conclusions: Zanu pts had significantly lower switching rate within 90 days and lower proportion of pts receiving next line of therapy at 180 days when compared with acala and ibru in 1L and 2L. Longer follow-up and larger zanu sample size are required for a comprehensive assessment of treatment outcomes associated with use of BTKis in CLL/SLL. [Table: see text]
Risk of stroke in patients with atrial fibrillation and chronic lymphocytic leukemia.
Authors: Yetiskul Ekrem , Rizvi Taqi , Khan Shahkar , Khan Salman , Alomari Omer , Agarwal Alaukika , Asmar Samer , Sah Sajan , Khattar Georges , Grabie Yisroel , Saliba Fares , Matra Amanda Marie , Mokhtar Asmaa , Dhar Meekoo , Bershadskiy Alexander , Khan Danyal F. , Mustafa Ahmad , Spagnola Jonathan , Parikh Valay K. 
Published: July 2024

e19030 Background: There has been a noticeable increase in the incidence of Atrial Fibrillation (AF) in patients with Chronic lymphocytic leukemia (CLL), especially patients treated with first-line therapy medications such as ibrutinib. However, these patients' risk of thromboembolic events is not well defined. Methods: Data for hospitalized patients with AF was obtained from The National Inpatient Sample (NIS) database from 2016-2018. Baseline risk factors were identified using ICD-10 codes. Patients who were already on anticoagulation were excluded. A logistic regression model was used to establish the relationship between variables and to adjust for underlying risk factors. The primary outcome was ischemic stroke between CLL and non-CLL patient cohorts. Results: The total number of patients was 1784456, out of which 1171644 patients were included in the study. There were 1165283 patients without CLL and 6361 with CLL. AF patients with CLL had more males (62.5% vs. 37.5%; P<.001), were older (74.6 vs. 78.82; P<.001), and had a lower prevalence of diabetes, hypertension, coronary artery disease, and hyperlipidemia. Pre-match analysis showed a lower rate of stroke in patients with AF and CLL compared to those without CLL (2.7% vs 4.2%; p<0.001). Post-match analysis revealed similar results with a lower risk of strokes in patients with CLL (4% vs 2.7%; p<0.001). Binary logistic regression analysis for primary and secondary outcomes revealed similar results pre-match and post-match. Patients who have AF and CLL had lower rates of stroke compared to those without CLL (OR: 0.647(0.530–0.790); p<0.001). Conclusions: AF patients with CLL were associated with a lower risk of ischemic stroke compared to those without CLL despite a higher risk profile as assessed by traditional risk factors. These findings should be considered while making decisions for therapies for the prevention of thromboembolic events.