bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell sequencing to elucidate the disparities in the immune microenvironment between PIK3CA mutants and wild types.
Authors: Xu Qin , Zhu Fei , Liu Jing , Chang Lele , Li Li , Zhu Mingxuan , Zhang Huiqi , Luo Lan , Zang Lele 
Published: July 2024

e17524 Background: In patients with cervical cancer, PIK3CA exhibits the highest mutation rate, with the predominant oncogenic alteration reported to occur in 40% of cases. Recent studies in cervical cancer have indicated that the mutation status of PIK3CA is prominently associated with a diminished overall survival. Nevertheless, in our preceding study entitled 'Efficacy and Safety of Sintilimab Plus Anlotinib for PD-L1–Positive Recurrent or Metastatic Cervical Cancer: A Multicenter, Single-Arm, Prospective Phase II Trial', the prognosis for the mutant group surpassed that of the non-mutant group. Therefore, distinguishing the differences in the immune microenvironment between PIK3CA mutant and wild-type cervical cancer patients is of great significance. Methods: We used Single-cell RNA sequencing (scRNA-seq) to analyze the tissue samples of 7 cervical cancer patients with PIK3CA mutations and 9 with wild-type. Results: We partitioned cells from both the mutated and wild-type forms of cervical cancer into nine distinct clusters. To better understand the transcriptional heterogeneity of tumor-infiltrating T lymphocytes, we re-clustered 45,574 NK/T cells into 9 clusters. A specific cell cluster, designated as CD8+ ISG15, exhibited a significant enrichment in interferon-induced genes, including ISG15, IFIT3, IFIT1, RSAD2, and IFI6. To explore intergroup differences, we performed differential analysis on the proportions of mutations and non-mutations in different subgroups. We found significant differences in CD8+ ISG15 between the mutant group and the widegroup. ISG15 plays a pivotal role in antiviral responses, and as research advances, it has been identified as a potential prognostic biomarker and therapeutic target for cancer, beyond its antiviral function. A growing body of studies indicates that ISG15 is overexpressed in the majority of tumors, however, the influence of high ISG15 expression on the overall survival of cancer patients is dependent on the cancer type. In our single-cell analysis of cervical cancer, we observed that the CD8+ ISG15 subgroup specifically expresses ISG15, and the prevalence of this subgroup is significantly greater in the PIK3CA wild-type group compared to the mutant group. Consequently, the CD8+ ISG15 subgroup is perceived as a significant subset within the cervical cancer immune microenvironment for regulating anti-tumor responses. Conclusions: We defined the CD8+ ISG15 cell cluster present in the cervical cancer immune microenvironment using scRNA-seq, and found that its proportion is significantly lower in the PIK3CA mutant group than in the wild-type group. Combined with existing research, this suggests that this subgroup plays an important role in immune regulation within the cervical cancer immune microenvironment.
Sintilimab and anlotinib combination therapy in PD-L1-positive recurrent/metastatic cervical carcinoma: A 3-year follow-up of ALTER-C201 study.
Authors: Xu Qin , Liu Jing , Chang Lele , Zhu Fei , Zhu Mingxuan , Zhang Huiqi 
Published: July 2024

e17526 Background: Sintilimab plus Anlotinib has been shown to be effective in advanced cervical cancer in the ALTER-C201 Study. Here, we report an updated, post-hoc analysis of overall survival from ALTER-C201 Study, after 3 years of follow-up. Methods: ALTER-C201 study was a multicenter, single-arm, prospective phase II trial. Patients with PD-L1–positive (Combined Positive Score ≥ 1) R/M CA who progressed after at least one prior systemic chemotherapeutic regimen or could not tolerate chemotherapy were eligible for the phase II trial. The patients received 200 mg sintilimab once on day 1 and 10 mg anlotinib once daily on days 1-14 every 3 weeks. The second endpoint was OS. The post-hoc analysis included Duration of Response (DoR), second progression-free survival (PFS2), as well as the efficacy of other treatments received by patients after disease progression. Results: Between December 2019 and December 2020, 42 patients were enrolled. We followed up for 38.0 (range, 0.6 - 44.0) months. The median overall survival was 17.59 months (95% CI, 12.831-36.163). Through multivariable analysis, it was found that PIK3CA (HR 3.430; 95%CI 1.040 - 11.310; P = 0.043) and KMT2C (HR 0.236; 95%CI 0.056 - 0.998; P = 0.049) are independent prognostic factors associated with overall survival (OS). In post-hoc analysis, the median DoR was 19 months (95%CI, 8.66 - not reach). Thirteen patients who experienced disease progression were subsequently treated with other anti-tumor therapies. Among them, nine received chemotherapy, three received radiotherapy, four received combination therapy with immune checkpoint inhibitors. The median PFS2 was 23.56 months (95%CI, 14.045 - not reach). The overall response rate (ORR) was 53.84%, with 2 patients (15.38%) achieving complete response (CR) and 5 patients (38.46%) achieving partial response (PR), Among the 4 patients who received immune checkpoint inhibitors, 3 of them achieved a partial response (PR). Conclusions: Sintilimab plus Anlotinib showed durable antitumor activity in patients with heavily pre-treated, PD-L1-positive advanced cervical cancer. PIK3CA and KMT2C may serve as potential prognostic biomarkers, but further studies are needed to validate their effectiveness. Patients who experience progression after treatment with the sintilimab plus anlotinib may still benefit from treatment with chemotherapy or combination therapy of other immune checkpoint inhibitors. Clinical trial information: ChiCTR1900023015.
Weekly BH009 in patients with squamous cell carcinoma of the head and neck (SCCHN) and ovarian cancer: Interim phase I results.
Authors: Wang Jing , Han Yaqian , Wang Ruoyu , Li Xiang , Kang Yu , Cheng Xiaobo , Chai Ranran , Jin Guanqin , Wei Xiaohua , Sun Qun 
Published: July 2024

e17545 Background: BH009 is a novel polysorbate 80-free formulation of docetaxel that will eliminate hypersensitivity reactions associated with polysorbate 80. BH009 has completed a bioavailability study compared to Taxotere and was found to have a better safety profile to Taxotere with the potential for higher doses. As a result, we conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD), and the safety profile of a weekly BH009 regimen in the treatment of patients with advanced SCCHN and Ovarian cancer. Methods: This phase I study assessed safety of BH009 in patients with advanced SCCHN and Ovarian cancer. BH009 was administered at escalating doses (starting dose 40 mg/m2) as a 1-h i.v. infusion for three consecutive weeks every 28 days without dexamethasone premedication. Results: Up to January 2024, 11 patients were treated with BH009 (4 at 40 mg/m2, 7 at 50 mg/m2). 2 patients with SCCHN, and 9 patients with ovarian cancer. 100% of ovarian cancer patients were recurrent platinum-resistant ovarian cancer (PROC) patients. 82% (9/11) of patients had received prior taxanes, of whom 33% (3/9) had received prior docetaxel. There were no DLT observed in 40 mg/m2 dose groups, and one DLT was observed in the 50 mg/m2 group (grade 3 febrile neutropenia). The MTD for BH009 is expected to exceed 50 mg/m2, which would be higher than that of Taxotere under the same dosing regimen (≥50mg/m2 vs 42mg/m2*), and the overall tolerability was better than Taxotere. In this study, treatment-related adverse events (TRAEs) occurred in 100% (11/11) patients. The most common grade 3/4 TRAEs were Leukopenia (36%, n=4), Anaemia (36%, n=4), and Neutropenia (55%, n=6). Non-hematologic toxicities were generally mild with no grade 4 toxicity observed. No AEs that led to death were related to BH009. Up to January 2024, the DCR is 50% (3/6) after 2 courses of treatment. The ORR in 6 evaluable patients was 33% (2/6, 1 patient with SCCHN at 40 mg/m2, 1 patient with ovarian cancer at 50 mg/m2). One patient (17%, 1/6) with ovarian cancer at 50 mg/m2 dose group received a complete response to the target lesion and the non-target lesion was partially responded after 2 courses of BH009, and this patient had been previously treated with docetaxel, carboplatin, and bevacizumab. Conclusions: The weekly BH009 for three consecutive weeks every 28 days is a feasible schedule with a favorable toxicity profile, and the overall tolerability is better than Taxotere. BH009 has the potential to increase the dose of administration and improve the clinical efficacy. Dose escalation is ongoing. Clinical trial information: NCT06232863 . [Table: see text]
Analysis of glycemia during olaparib therapy in patients with ovarian cancer.
Authors: Stanislawiak-Rudowicz Joanna , Szalek Edyta , Czyrski Andrzej , Grzeskowiak Edmund , Madry Radoslaw 
Published: July 2024

e17559 Background: Olaparib (poly(ADP-ribose) polymerase inhibitor) is a relatively new anticancer drug and some of its metabolic side effects, such as its effect on blood glucose, are not yet well defined. The aim of the study was a retrospective analysis to investigate olaparib-induced changes in glucose levels in patients with ovarian cancer (OC). Methods: The study was conducted on 32 OC patients with normoglycemia (3.9–5.5 mmol/l) confirmed before olaparib treatment. The fasting glucose (FG) levels were estimated after I (one month), II (two months), and III (three months) courses of olaparib treatment. The severity of hyperglycemia was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Results: During treatment with olaparib, grade 1 hyperglycemia was found in 18 patients (56.2%), therefore hemoglobin A1C level measurement was recommended. The number of patients with impaired fasting glucose (5.6–6.9 mmol/l), characteristic of a pre-diabetic state, was 17 (53.1%), while glycemia indicative of diabetes (≥7.0 mmol/l) were found in 1 patient (3.1%). The statistically significant increase in glycemia was observed after I course of treatment (p< 0.0001), then after the second (p=0.0003), and III course (p=0.0025). Conclusions: During olaparib therapy, hyperglycemia was observed in 56.2% of the analyzed OC patients, implying the need for glycemic monitoring during monthly routine check-ups to implement effective behavioral and therapeutic management.
Efficacy of compound pholcodine syrup and compound codeine phosphate oral solution on lung cancer cough.
Authors: Yu Huiqing , Chen Mengting , Zhang Junhui , Yang Hong 
Published: July 2024

e20548 Background: To assess the therapeutic effect of compound pholcodine syrup and compound codeine phosphate oral solution on lung cancer cough. Methods: A total of 60 patients with diagnosed middle-advanced stage lung cancer accompanied with lung cancer cough from Jan, 2022 to May, 2022 were enrolled . According to the method of random number table, the patients were divided into two groups: observation group and control group. Observation group received compound pholcodine syrup treatment, while control group received compound codeine phosphate oral solution treatment. The dosage of the two drugs was 15 ml each time, 3 times a day, and the treatment course was 5 days. The antitussive effectiveness, cough severity and quality of life , were observed and compared between the two groups before and after the 3 days and 5 days treatment, respectively. Results: All 60 patients completed the treatment. Both two groups were effective in controlling lung cancer cough. After the 3 days treatment, the antitussive effective rates of the observation group and the control group were 83.3% (25/30) and 73.3% (22/30), respectively, with no statistical significance ( P= 0.347). After the 5 days treatment, the antitussive effective rates of observation group and control group were 90.0% (27/30) and 86.6% (26/30), respectively, with no statistical significance ( P= 0.687). There was no significant difference in the composition of patient cough severity between observation group[moderate and severe cough, 56.7% (17/30) ] and control group [moderate and severe cough, 67.7% (20/30) ]. After 3 days treatment, cough symptoms were relieved in both groups. Patients with mild cough accounted for 73.3% (22/30) in the observation group and 56.7% (17/30) in the control group, the difference was not statistically significant ( P= 0.331). What's more, after 5 dyas treatment, there was also no significant difference( P= 0.067)between observation group[mild cough, 86.7%(26/30)] and control group [mild cough, 66.7%(20/30)] . In the meantime, there were no significant differences in the physiological score, psychological score, social score and total score of the Leicester Cough Questionnaire in Mandarin-Chinese scale before the treatment, after 3 days and 5 days treatment between the two groups (all P > 0.05). Patients in the observation group had a lower incidence of xerostomia (0.0% vs 20.0 %, P= 0.024) and constipation (0.0% vs 20.0 %, P= 0.024) than control group. Conclusions: Compound pholcodine syrup and compound codeine phosphate oral solution are effective in treating lung cancer cough with similar antitussive effectiveness. Compound pholcodine syrup has a lower incidence of xerostomia and constipation than control group, which indicates that the security may be better. Clinical trial information: ChiCTR2300076684.
Predictors of immediate and delayed cutaneous hypersensitivity reactions to paclitaxel.
Authors: Trager Megan Hannah , Kuo Alyce Mei-Shiuan , Dusza Stephen W. , Park Vivian , Geskin Larisa J. , Guyer Autumn , Abuhadra Nour , Gucalp Ayca , Lacouture Mario E. 
Published: July 2024

e24101 Background: Paclitaxel is one of the first-line treatments for breast, ovarian, and lung cancers. However, its use is limited by the high frequency of hypersensitivity reactions. The purpose of the current study was to assess clinical factors associated with immediate and delayed hypersensitivity reactions to paclitaxel and characterize delayed hypersensitivity reactions to paclitaxel in patients with breast cancer. Methods: We conducted a retrospective chart review of patients who received paclitaxel (Taxol) or nab-paclitaxel (Abraxane) between 1/1/2017 and 1/1/2022 at Memorial Sloan Kettering Cancer Center. Results: In total, 12,274 patients were identified who were treated with paclitaxel. Of these, 6,165 had breast cancer and 1,233 were seen by a dermatologist. 734 patients (11.9%) developed an immediate hypersensitivity reaction to paclitaxel. Age (p < 0.001), race (p < 0.001), and prior history of allergy based on prior ICD-10 code (p = 0.05) were significantly associated with immediate hypersensitivity reactions. Patients who developed an immediate HSR (mean 52.5 ± 12.5 years versus 54.8 ± 12.9 years) tended to be younger, on average, than those who did not experience a reaction. Compared to White patients, Black patients were 37% less likely (OR = 0.63; 95% 0.48 – 0.83) and Asian patients were 70% more likely (OR = 1.70; 95% 1.37 – 2.12) to experience a hypersensitivity reaction. 147 patients (4.0%) had a delayed hypersensitivity reaction (cutaneous rash). Delayed hypersensitivity reaction included toxic erythema of chemotherapy, urticaria, morbilliform, maculopapular, and pruritus phenotypes. The most common phenotypes were maculopapular (52%) and urticaria (36%). The majority had not been treated with nab-paclitaxel prior to rash (86%). Race (p < 0.001) and history of allergy (p < 0.001) were associated with development of a cutaneous reaction. Asian patients were almost twice as likely (OR = 1.99; 95% CI: 1.51 - 2.61, P < 0.001) as White patients to present with a delayed HSR to paclitaxel. Patients with an immediate hypersensitivity reaction were more likely to develop a delayed cutaneous reaction (OR = 1.80; 95% confidence interval: 1.27-2.55) than those who did not get an immediate HSR, controlling for breast cancer stage and patient race. Conclusions: In conclusion, risk factors identified for development of immediate hypersensitivity reactions in this study were younger age, Asian race, and history of allergy. Patients who developed an immediate hypersensitivity reaction were more likely to develop a delayed hypersensitivity reaction. Risk factors for development of the rash included Asian race and history of allergy. Awareness of these clinical factors which are associated with development of a rash could guide providers in choosing treatment with paclitaxel or nab-paclitaxel.
Real world data of safety of immune-checkpoint inhibitors in patient with cancer at tertiary care hospital in Saudi Arabia.
Authors: Alanazi Ahmed , Alzaharani Iman , Bashir Mohammed Salman , AlNajjar Fouad H. 
Published: July 2024

e24104 Background: Immune checkpoint inhibitors (ICIs) become an integral part of many cancer therapies, such as melanoma, esophageal carcinoma, breast cancer and other malignancies. Immune checkpoint inhibitors work by activation the immune system that blocks negative regulators expressed on immune or tumor cells. Accordingly, the mechanism of action of ICI may cause autoimmunity-like symptoms called immune-related adverse events (irAEs) that affect many organs in body like skin, liver, lung, endocrine and gastrointestinal tract. These irAEs may reduce the organ function, quality of life and it may cause death. The present work addressed the knowledge gap in understanding real-world outcomes of irAEs associated with ICIs. Real-world patients are more diverse than clinical trial. Methods: This retrospective cohort study investigated the use of immune checkpoint inhibitor (ICI) therapy in an oncology and hematology patients treated at King Fahad Medical City (KFMC) comprehensive cancer center between February 2021 and February 2023. Adult patients (≥ 18 years old) diagnosed with any malignancy or hematological disorder who received at least one dose of ICI therapy during the study period have been included. Patients younger than 18 years old have been excluded. Demographic, clinical, and treatment data have been extracted from the electronic medical records (EMR). The study protocol has been reviewed and approved by the KFMC Institutional Review Board (IRB). The trial still undergoing not yet finished. Results: A total of 44 patients were included by the time preliminary data analysis was conducted on January 1st, 2024. All Patient included were receiving Pembrolizumab 44 patients. In regards to demographics, 27 (61.4%) of the patients were female. Breast cancer was the most common diagnosis (34.1%), followed by non-small cell lung cancer (22.7%). Among patients undergoing ICI, 34.1% had at least one Emergency Room (ER) visit. Notably, 25% of these patients had 1-2 ER visits. The most common reason for ER visits was patient complaints of GI toxicity related to ICI, including nausea, vomiting, and diarrhea (colitis). 12 (26.8%) patients required hospitalization, and 9 (20.5%) stayed for more than seven days.The time to first adverse event of ICI therapy was most commonly seen after nine weeks in 8 (18.2%) patients. Hypothyroidism was the most common adverse event (11.4%), followed by gastrointestinal toxicity (6.8%). Skin, grade 2 hepatotoxicity, and renal toxicity were also reported in 1 (2.3%) patient respectively. Conclusions: Overall, this initial analysis suggests that while ICI known to offers promising potential, it also carries the risk of various adverse events, including a significant rate of ER visits and hospitalizations. Further investigation with larger patient cohorts is warranted to confirm these findings and optimize IO therapy management.
Acute pancreatitis secondary to tamoxifen-induced hypertriglyceridemia: A systematic review.
Authors: Hussain Ali , Zareef Sumaira , Isaac Sangeetha , Arora Aakriti , Valasapalli Srijan , Paracha Munizay , Tasleem Azka , Mainkar Nayan , Muzaffar Mahvish 
Published: July 2024

e24105 Background: Tamoxifen can cause paradoxical effects on lipid metabolism and increase triglyceride levels. Acute pancreatitis (AP) can culminate in increased severity and morbidity. A multitude of secondary etiologies may lead to hypertriglyceridemia (HTG), including alcohol, pregnancy, diabetes mellitus, or medications. Tamoxifen is known to cause HTG, but AP as a sequel to this complication remains exceedingly rare. Methods: We performed a systematic search of MEDLINE, Cochrane, Embase, and Google Scholar by using MeSH terms and keywords "tamoxifen," "acute pancreatitis," and "hypertriglyceridemia" from tamoxifen approval in 1977 to December 2023. A total of 26 cases were identified. The diagnosis of AP was established on meeting two of the three Revised Atlanta Classification criteria. Results: A total of 17 case reports fulfilled our inclusion criteria. The mean age of included patients was 35.84 ± 5.99 years. Clinical presentation was mainly related to vomiting (65%), abdominal pain (59%), nausea (47%), and epigastric discomfort (18%). HTG (55%), diabetes mellitus (27%), and hypertension (18%) were major comorbid conditions. The mean onset delay was 11.81 ± 14.75 months, and the tamoxifen dose was 20 mg per day. AP was categorized into mild (35%), moderate (35%), or severe (30%) forms. Treatment mainly consisted of conservative measures, but intravenous insulin (24%) and plasmapheresis (6%) were used in severe cases. The overall mortality rate was 6%. Conclusions: Tamoxifen-induced hypertriglyceridemic pancreatitis is a potential complication of tamoxifen therapy. The findings underscore the need for regular monitoring of serum lipids in these patient patients, especially those with pre-existing HTG or other comorbid conditions that increase their risk of developing hypertriglyceridemic pancreatitis. By implementing these recommendations, clinicians can help reduce morbidity and mortality associated with this condition. [Table: see text]