bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of immune checkpoint inhibitors in PDL1-negative, low TMB, stable MSI metastatic solid tumours: Single centre study.
Authors: Moorthy Vijay , T P Sharafudheen , Kumar Delvin , Dasgupta Roshni , Naseer Mohammed , B.J Srinivas , Tripathi Priyank , Radheshyam Naik , Patil Shekar , Thungappa Satheesh Chiradoni , Nagaraj Madhu , Munaf Sajad , Naidu Srinivas , Shah Mansi , Sanghavi Niyati Prakash , Thippeswamy Ravi , krishna S Adithya , Reddy Spoorthi , Kumar Goutham , Vithal Yergolkar Abhijna ,   HCG BENGALURU
Published: June 2023

e14603 Background: Immune check point inhibitors clearly play a part in malignancies with elevated PDL1 expression, high TMB or unstable MSI. There is no information on PDL1 negative, low TMB/MSI stable metastatic solid tumours, however several treatment trials advise using immune check point inhibitors regardless of tissue agnostic indicators. Detailed subset analysis was not performed, though. This study examines the effectiveness of immunotherapy in metastatic solid tumours with PDL1 negative/TMB low/MSI stability. Methods: Study was carried out from Jan-2020 to Dec- 2022 (retrospective data from 2019 also included for analysis). Inclusion criteria: Metastatic solid tumours in patients who received immunotherapy. Exclusion criteria: PDL1>1% ( Either TPS/ CPS >1) by sp263 or 22c3 platforms, TMB> 10, Unstable MSI by IHC or by genomics. Patients who were diagnosed with melanoma, hepatocellular cancer, renal cell carcinoma were also excluded from the study. Response was initially assessed after 3 to 6 cycles of immunotherapy, analysed by PET CT scan. Data were analysed using standard statistical method. Results: After carefully applying exclusion criteria, a total of 40 patients were enrolled in the research, with a male to female ratio of 1.5. Overall response rate in all tumours was 17.5% (7/ 40) Immune checkpoint inhibitors' ORRs at various tumour locations. Among the responders head and neck tumours 2/4 (50%) and lung cancers (37.5%) had higher ORR who also had greater depth of response, living more than 2 years from diagnosis. There is no response observed in gastroesophageal (0/8) gynaecological malignancies (clear cell ovary (0/2), endometrial and cervical (0/3). A patient with urothelial carcinoma who also had a BRCA mutation and was one out of seven responded to IO. Conclusions: Regardless of the presence of PDL1 expression, high TMB, or MSI, adding immune checkpoint inhibitors to the treatment regimen for metastatic head and neck malignancies and lung tumours that lack driver mutations is obviously advantageous. On the other hand, immunotherapy had no effect on gastrointestinal, gynaecological, or urothelial tumours. To validate these findings, more research with several centres and a sizable sample size is necessary. It's interesting that one patient responded to immunotherapy with positive BRCA mutation. Investigating immunotherapy in HRR deficient tumours may shed further insights. [Table: see text]
Use of tumor mutational burden as a predictive marker of response to immuno-oncology agents: Initial experience at an academic center in Venezuela.
Authors: Borga Guillermo , Sucre Santiago , Sucre Oscar , Vivas Liliam , Salazar Hector , Sucre Carlos Eduardo 
Published: June 2023

e14613 Background: Tumor Genetic Profiling (TGP) is steadily becoming the mainstay of clinical practice, namely, the Tumor Mutational Burden (TMB) is believed to be a predictor of efficacy to treatment with Immune Checkpoint Inhibitors (ICI). Recent studies have demonstrated that a high-TMB score (TMB-H) is associated with higher response rates. In Venezuela, the evidence of mutational frequencies obtained by TGP is limited, herein we present our experience at a large educational institution. Methods: In this retrospective cohort, we included 80 subjects with different types of solid tumors to whom TGP was performed to determine TMB values, as well as other associated mutations, between January 2020 and December 2022. In a subgroup of subjects in which ICI therapy was formally indicated (n=21) we used the Objective Response Rate (ORR) as a primary endpoint, recorded as the percentage of patients who had a complete response (CR) or partial response (PR), based on the RECIST v1.1 criteria. Treatment options included Ipilimumab, Atezolizumab, Pembrolizumab and Nivolumab, as either monotherapy or in combination according to the corresponding NCCN guidelines. A TMB-H score was defined as greater than 10 mutations per megabase. Results: A TMB-H was found in 11 samples, subjects with lung cancer accounted for the majority of this finding (n=6). The most frequently reported mutations were BRCA 1-2 (n=9), KRAS (n=9), and EGFR (n=4). In the subgroup treated with ICI, the ORR of the group with TMB-H was 71.42%, while in those with low TMB it was 35.71%. The differences in response rates, with a 95% CI, yielded a p=0.122; which corresponds to a statistically non-significant outcome. Conclusions: This study constitutes the first country-level documentation of what is becoming a standardized practice, and contributes to the growing evidence regarding the use of TMB-H as a marker to predict response to treatment. Our small cohort demonstrated a high ORR to ICI when a TMB-H score is present, albeit to a non-statistically significant degree. We will continue to follow-up these patients, as well as to include newly sequenced samples for TGP, to give greater statistical power to these findings.
Effect of FAPα-expressing tumor cell vaccine with PD-1 mAb on its efficacy in mice colorectal cancer model.
Authors: Jia Hongyuan , Chen Meihua , Xiao Ling , Li Tao , Lang Jingyi 
Published: June 2023

e14615 Background: Colorectal cancer (CRC) is the third prevalent malignant tumor all over the world, and many cases are metastatic at diagnosis. Immunotherapy emerges a promising treatment in CRC. However, anti-PD-1 monotherapy alone has not yielded a clinical benefit in majority of these patients. Therefore, combination therapy is necessary to overcome this limitation. Previously, we have developed a FAPα-expressing tumor vaccine and demonstrated its anti-tumor effects by reversing of immunosuppressive tumor microenvironment (TME). In the current study, we hypothesized that combination therapy could enhance the effect of anti-PD1 therapy. Methods: FAPα-expressing CT26 cells were produced as previously described. To establish xenograft tumor model, CT26 cells were injected into left flank of BALB/c mice. Anti-PD-1 monoclonal antibodies(mAb) were injected intraperitoneally twice weekly up to 5 injections. FAPα-vaccines were injected subcutaneously around tumors weekly up to 3 injections. Histological sections of tumours were analysed by H&E staining and immunofluorescence. Flow cytometric analysis was done using an FACSCalibur (BD) and analyzed using FlowJo software (TreeStar). Gene expression profile in TME was analyzed by bulk RNA sequencing. Results: In mice xenograft CT26 tumor model, either anti-PD-1 immunotherapy or FAPα tumor cell vaccine produced suppression of CT26 tumor growth compared with the control group. However, combining anti-PD-1 mAb and FAPα-expressing tumor cell vaccine elicited the most remarkable anti-tumor effect and induced the most pronounced tumor growth suppression among all groups. In combination therapy group of the vaccine and PD-1 mAb, there were significantly more infiltrated lymphocytes and less FAPα+ fibroblasts. Flow cytometry demonstrated that the combination therapy promoted M1 macrophage polarization with a reduction of M2-like tumor associated macrophages (TAMs) and an increase of M1-like TAMs. This polarization was in consistent with the reduced level of IL-10 that is predominant cytokine secreted by M2 macrophages. A reduction of myeloid-derived suppressor cells (MDSCs) in the TME were also observed. Using bulk RNAseq we observed a set of immune related genes upregulated following combination therapy, including innate immune response, antigen presentation, lymphatic cells and recruitment and T cells activation. Decreased secretion of immune inhibitory chemokines (eg, CXCL12, IL-10, TGFβ) was also found by ELISA in tumors from mice treated with combination therapy. Conclusions: Our preliminary results suggested that combination therapy of FAPα-expressing tumor vaccine and anti-PD-1 therapy is a promising way to improve the efficacy of immunotherapy through modulation of immunosuppressive TME. In the future, more research is needed to further elucidate mechanism and clinical value of this combination approach.
Atezolizumab plus bevacizumab combined with transarterial embolization plus hepatic arterial infusion-chemotherapy for unresectable hepatocellular carcinoma with a diameter larger than 8 cm: A retrospective study.
Authors: Guo Wenbo , Cai Hongjie , Chen Song , Wu Zhiqiang , Wang Fan , Chen Ludan , Tang Shuangyan , Zhuang Wenquan 
Published: June 2023

e14617 Background: The combination of atezolizumab and bevacizumab (Atezo-Bev) has become the standard first-line therapeutic regimen for patients with unresectable hepatocellular carcinoma (uHCC), while the therapeutic effect is limited in patients with high-risk characteristics (vp3/vp4 portal vein tumor thrombus or high tumor burden). Locoregional therapy plays an important role in minishing tumor burden and synergistic antitumor effect with systemic therapy, including transarterial embolization (TAE) and hepatic arterial infusion chemotherapy (HAIC). Herein, this study aimed to assess the efficacy and safety of atezolizumab and bevacizumab combined with TAE and HAIC in unresectable hepatocellular carcinoma with high tumor burden. Methods: This retrospective study reviewed the medical records of patients who had primary uHCC with high tumor burden (maximum nodule diameter >8 cm) receiving Atezo-Bev plus TAE and HAIC from September 2019 to September 2022 in our medical center. HAIC involved oxaliplatin, fluorouracil and leucovorin (FOLFOX regimen). Progression-free survival (PFS), overall survival (OS), tumor response according to mRECIST, and treatment-related adverse events (AEs) were evaluated. Results: In total, 30 patients were included in this study with a median follow-up period of 11.4 months. Twelve patients (40%) died and all the remaining patients reached the end point of PFS at the cut-off follow-up time. The median PFS of the 30 evaluable patients was 6.8 months (95% CI, 2.6-11.1 months), and the survival rates at 3 months, 6 months, 9 months, and 12 months were 86.2%, 82.5%, 68.6%, and 60%, respectively, and the median OS was not estimated (NE). According to the mRECIST, the objective response rate (ORR) was 74.4% (95% CI, 59.3%-89.5%), and the disease control rate (DCR) was 93.3% (95%CI, 85.4%-98.6%) respectively. Extrahepatic metastasis was an independent risk factor associated with PFS.As for the safety, there was no treatment-related mortality throughout the study period. The most common AEs were fever (6.7%), and diarrhoea(6.7%), and grade 3/4 AEs occurred among 6 patients (20%). Conclusions: Atezo-Bev combined with TAE and HAIC may be safe and effective for uHCC patients with high tumor burden, while further prospectively clinical research is necessary to validate the efficacy and safety.
Immune checkpoint inhibitors-associated periodontitis: A propensity score-matched retrospective cohort study.
Authors: Hsia Yuanping , Chiang Cho Hsien , Chiang Cho Han , Chiang Cho Hung , Peng Cheng-Ming , Shiah Her-Shyong , Ma Kevin Sheng-Kai 
Published: June 2023

e14618 Background: Immune checkpoint inhibitors (ICIs) have been associated with a wide spectrum of immune-related adverse events (irAE) including oral mucositis and xerostomia. Periodontitis is another form of common oral pathology characterized by severe gingival inflammation but has not been investigated in patients receiving ICIs. We aimed to evaluate the risk of periodontitis associated with the use of ICI and to determine the clinical outcome of ICI-associated periodontitis. Methods: We conducted a 1:1 propensity score-matched retrospective cohort study involving patients receiving ICIs between January 2010 and November 2021. The primary outcome was periodontitis and the secondary outcomes were overall survival (OS), progression-free survival (PFS), and objective response rates. The propensity score matching was performed using basic demographics, underlying comorbidities, cancer type, and cancer therapy. The risk of periodontitis and associations between periodontitis and survival were evaluated using Cox proportional hazard analysis and Kaplan-Meier survival analysis. Results: We matched 868 patients receiving ICIs to patients who did not receive ICIs. Among ICI users, 41 (4.7%) patients developed periodontitis. The incidence rate of periodontitis was about 2-fold higher in ICI users than non-users (55.3 vs 25.8 per 100 patient-years; incidence rate ratio: 2.1 [95% CI: 1.4-3.3], p < 0.001). In Cox regression analyses, the use of ICI was associated with an 80-90% increased risk of periodontitis. The presence of immune-related periodontitis was associated with improved OS (median not reached vs. 17.8 months, p < 0.001), PFS (median 14.9 vs. 5.6 months, p = 0.009), and objective response rates (complete or partial response, 55% vs. 27%, p < 0.001). In Cox regression analyses, ICI use was associated with a 30-60% lower risk of all-cause mortality or disease progression. Conclusions: ICIs were associated with an increased risk of periodontitis. ICI-related periodontitis was associated with better survival outcomes and treatment responses.[Table: see text]
Biliary intervention combined with lenvatinib+ PD-1 inhibitor of Klatskin tumor complicated with malignant obstructive jaundice.
Authors: Fu Xiaobo , Mu Maoyuan , Qi Han , Jiang Weiwei , Chen Zixiong , Gao Fei 
Published: June 2023

e14620 Background: Hilar Cholangiocarcinoma (Klatskin tumor) is a rare and highly aggressive cancer that occurs at or near the junction of the right and left hepatic ducts. Gemcitabine + cisplatin has been established as an effective first-line treatment. However, this malignancy is commonly complicated by malignant biliary obstruction which may gradually damage patients’ liver function and may limit the chemotherapy. In addition, Cumulative clinical evidence showed that tyrosine kinase inhibitor (TKI) combined with immunotherapy is represented as a promising alternative. This study aimed to evaluate the clinical value of biliary intervention combined with the Lenvatinib+PD-1 inhibitor (Tislelizumab/Sintilimab) for the Klatskin tumor. Methods: From January 2020 to December 2022, 21 Klatskin tumor patients with malignant hilar biliary obstruction (MHBO) were included. All included patients received biliary decompression by metal stent + Iodine-125 seed strand (ISS) implantation. The number of 125I seeds to be implanted was determined according to the plan of the preoperative computerized treatment planning system (TPS). The procedure-related outcomes were evaluated regarding successful drainage and complications. In addition, the survival of patients who received successful biliary drainage and patients who received sequential systemic anticancer treatment were analyzed. Successful biliary drainage was defined as the serum total bilirubin level dropped by 75% of the preoperative value within 4 weeks. Major complications referred to those that result in death or serious adverse effects including sepsis, uncontrollable biliary or intestinal bleeding, and acute renal failure. The time between stent insertion and death was defined as patient survival. Results: 71.4% achieved successful drainage, significant improvements were observed from before to one month after the procedure in liver function values, including total bilirubin (TBIL), and direct bilirubin (DBIL) (all P<0.001). Minor complications occurred in 5 patients (23.8%) in all patients, including 1 patient (4.8%) who experienced cholangitis, and 4 patients (19%) who suffered abdominal pain. No major procedure-related complication was observed. The median overall survival(mOS) of 21 patients was 6.1 months. Patients who received successful biliary drainage (n=15) had longer mOS than those who received unsuccessful biliary drainage(n=6) [7.4 months vs. 3.5 months, respectively, P<0.001]. Patients who received sequential Lenvatinib+ Pembrolizumab after effective drainage(n=9) had longer mOS than those who only received palliative therapy(n=6) [7.4 months vs. 5.2 months, respectively, P=0.028]. Conclusions: Biliary intervention + ISS combined with the following Lenvatinib+ PD-1 inhibitor is safe and feasible for cholangiocarcinoma patients complicated with obstructive jaundice.
TIPS combined with lenvatinib and PD-1 inhibitor in patients with advanced HCC with symptomatic portal hypertension: A retrospective study.
Authors: Mu Maoyuan , Fu Xiaobo , Qi Han , Jiang Weiwei , Chen Zixiong , Gao Fei 
Published: June 2023

e14628 Background: Symptomatic portal hypertension (SPH) leads to a poor prognosis as a common complication in advanced hepatocellular carcinoma (HCC) patients due to cirrhosis or portal vein tumor thrombus. Although combined therapy including Lenvatinib and PD-1 inhibitors has shown valuable advantages in advanced HCC, the above strategy is limited by liver function impairment due to SPH complications such as variceal bleeding and refractory ascites. Transjugular intrahepatic portosystemic shunt (TIPS) directly relieves portal hypertension which may create a chance for advanced HCC patients with SPH to receive systemic therapy. Thus, TIPS plus following Lenvatinib and PD-1 inhibitor may serve as an effective anticancer modality. This study aimed to evaluate the efficacy and safety of TIPS combined with Lenvatinib and PD-1 inhibitor for advanced HCC patients with SPH. Methods: This retrospective study included thirteen advanced HCC with SPH patients who received TIPS combined with Lenvatinib and PD-1 inhibitor (Tislelizumab/Sintilimab) between January 2020 and January 2023. Main inclusion criteria: a confirmed HCC (BCLC stage C) based on the AASLD with either pathological or imaging findings; no previous systemic anticancer treatment; Child-Pugh score ≤10; ECOG status: 0-1. Portal hypertension with complications (variceal bleeding, refractory ascites). The outcome measures included objective response rate (ORR) (assessed with mRECIST v1.1), disease control rates (DCR), progression-free survival (PFS), overall survival (OS), SPH recurrence rate, and safety. Drug safety was investigated according to CTCAE (version 5.0). Results: With a median follow-up of 6.5 months (range 2.3-19.0), 13 patients with a median age of 57 years (range: 33-70) were evaluable for response and toxicity. 3 (23.1%) patients with Tislelizumab and 10 (76.9%) with Sintilimab. 7 (53.8%) patients were classified as Child-Pugh A class. According to mRECIST v1.1, ORR was 38.5% (95%CI, 11.8%-61.6%) with 1CR and 4 PR, and the DCR was 53.8% (95%CI, 21.3%-73.4%). The median overall survival (OS) was 16.5 months (95%CI,16.1-17.0). The prevalence of rebleeding, ascites and hepatic encephalopathy, was 7.7 %, 15.4%, and 7.7%, respectively. Treatment-related adverse events were confined to grades 1-2 occurring in 3/13 (23.1%) patients as rash (2, 15.4%) and fatigue (1, 7.7%). There were no treatment-related serious adverse events. Conclusions: TIPS combined with Lenvatinib and PD-1 inhibitor demonstrated a valuable anti-cancer strategy for advanced HCC patients with SPH based on the low recurrence rate of SPH and acceptable side effects.
Comparison of two ICI-based microtubule antagonist therapies for high-risk, non-muscle-invasive bladder cancer.
Authors: Niu Yuanjie , Hu Hailong , Li Hong Zheng , Shen Chong , An Zesheng , Wu Zhouliang , Zhang Zhe , Huang Shiwang , Zhao Gangjian , Guo Shizheng , Chen Houyuan , Jia Kaipeng 
Published: June 2023

e14629 Background: Patients with highly extensive non-muscle-invasive bladder cancer (NMIBC) whose invasion area is too vast to be removed through TURBT should receive radical cystectomy in clinical practice. Clinical practice showed that nab-paclitaxel (Nab-P) or RC48-ADC (Disitamab Vedotin, DV) in combination with tislelizumab (BGB-A317, immune checkpoint inhibitor, ICI) had good effects on these patients with acceptable adverse events (AEs). This study was to compare the efficacy and safety of these two regimens. Methods: Retrospectively collected and analyzed data from two single-center clinical trials. Eligible patients were aged 18 years or older with unresectable NMIBC who received their first dose of Nab-P/ICI or DV/ICI between July 2020 and December 2022. The primary outcome was the pathological complete response (pCR) rate in a propensity score matching (PSM) population that was performed matching using a 1:4 ratio for the DV/ICI and Nab-P/ICI groups by propensity score. The main secondary outcome was treatment-related adverse events (trAEs), assessed in all eligible populations. Results: The eligible population was 12 for DV/ICI and 69 for the control group (Nab-P/ICI). The PSM population was 12 for DV/ICI and 48 for Nab-P/ICI. pCR was 66.7% (39.1%-86.2%) for DV/ICI and 60.4% (46.3%-72.9%) for the Nab-P/ICI group (OR: 0.76; 95% CI: 0.23–2.78; Fisher's exact test P = 0.75) in the PSM population. The most common trAE in the Nab-P/ICI group was alopecia, and the incidence was significantly lower in DV/ICI (Fisher's exact test, P < 0.05). Grade 3–4 trAEs were observed at 8.70% and 8.33% in Nab-P/ICI and DV/ICI, respectively. No trAE-related deaths were reported. Conclusions: The pooled results of the two studies with the efficacy and safety data showed promising ICI-based microtubule antagonist regimens in pts with highly extensive non-muscle-invasive bladder cancer (NMIBC), and DV/ICI may be preferred by pts for the low incidence of alopecia in clinical practice.