bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 vaccination in advanced skin cancer patients receiving systemic anticancer treatment: A prospective singlecenter study investigating seroconversion rates
Authors: Lodde Georg C. , Fiedler Melanie , Dittmer Ulf , Placke Jan-Malte , Jansen Philipp , Becker Jürgen C. , Zimmer Lisa , Livingstone Elisabeth , Schadendorf Dirk , Sondermann Wiebke , Ugurel Selma 
Published: August 2022

BackgroundCOVID-19 vaccination reduces risk of SARS-CoV-2 infection, COVID-19 severity and death. However, the rate of seroconversion after COVID-19 vaccination in cancer patients requiring systemic anticancer treatment is poorly investigated. The aim of the present study was to determine the rate of seroconversion after COVID-19 vaccination in advanced skin cancer patients under active systemic anticancer treatment.MethodsThis prospective single-center study of a consecutive sample of advanced skin cancer patients was performed from May 2020 until October 2021. Inclusion criteria were systemic treatment for advanced skin cancer, known COVID-19 vaccination status, repetitive anti-SARS-CoV-2-S IgG serum quantification and first and second COVID-19 vaccination. Primary outcome was the rate of anti-SARS-CoV-2-S IgG seroconversion after complete COVID-19 vaccination.ResultsOf 60 patients with advanced skin cancers, 52 patients (86.7%) received immune checkpoint inhibition (ICI), seven (11.7%) targeted agents (TT), one (1.7%) chemotherapy. Median follow-up time was 12.7 months. During study progress ten patients had died from skin cancer prior to vaccination completion, six patients were lost to follow-up and three patients had refused vaccination. 41 patients completed COVID-19 vaccination with two doses and known serological status. Of those, serum testing revealed n=3 patients (7.3%) as anti-SARS-CoV-2-S IgG positive prior to vaccination, n=32 patients (78.0%) showed a seroconversion, n=6 patients (14.6%) did not achieve a seroconversion. Patients failing serological response were immunocompromised due to concomitant hematological malignancy, previous chemotherapy or autoimmune disease requiring immunosuppressive comedications. Immunosuppressive comedication due to severe adverse events of ICI therapy did not impair seroconversion following COVID-19 vaccination. Of 41 completely vaccinated patients, 35 (85.4%) were under treatment with ICI, five (12.2%) with TT, and one (2.4%) with chemotherapy. 27 patients (65.9%) were treated non adjuvantly. Of these patients, 13 patients had achieved objective response (complete/partial response) as best tumor response (48.2%).Conclusion and relevanceRate of anti-SARS-CoV-2-S IgG seroconversion in advanced skin cancer patients under systemic anticancer treatment after complete COVID-19 vaccination is comparable to other cancer entities. An impaired serological response was observed in patients who were immunocompromised due to concomitant diseases or previous chemotherapies. Immunosuppressive comedication due to severe adverse events of ICI did not impair the serological response to COVID-19 vaccination.
Periodontal disease and cancer risk: A nationwide population-based cohort study
Authors: Kim Eun Hwa , Nam Sunghyun , Park Chung Hyun , Kim Yitak , Lee Myeongjee , Ahn Joong Bae , Shin Sang Joon , Park Yu Rang , Jung Hoi In , Kim Baek-Il , Jung Inkyung , Kim Han Sang 
Published: August 2022

BackgroundAlthough emerging evidence suggests that periodontitis might increase the risk of cancer, comorbidity and lifestyle behaviors, such as smoking and body mass index (BMI), may have confounded this reported association. This study aimed to investigate whether chronic periodontitis is associated with cancer risk using a large, nationwide database.MethodsWe conducted a population-based, retrospective cohort study using data from the Korean National Health Insurance Cohort Database obtained between January 2003 and December 2015. We included 713,201 individuals without a history of cancer who were followed up to 10 years. Confounding factors included demographic factors (age, sex, income, and residential area), lifestyle behaviors (smoking history and BMI), and comorbidities, such as hypertension, diabetes, heart failure, and pulmonary disease, using the Charlson Comorbidity Index. Multivariable Cox regression analysis was applied to estimate the adjusted hazard ratio (aHR) for cancer risk.ResultsOf the 713,201 participants, 53,075 had periodontitis and were placed in the periodontitis group; the remaining 660,126 individuals were included as the control group. Overall, the cumulative incidence of cancer in the periodontitis group was 2.2 times higher than that in the control group. The periodontitis group had an increased risk of total cancer compared to the control group after adjusting for age, sex, comorbidities, BMI, and smoking history (aHR, 1.129; 95% confidence interval [CI], 1.089-1.171; P&lt;0.0001). When examining specific cancer types, significant associations were also observed between periodontitis and stomach cancer (aHR, 1.136; 95% CI, 1.042-1.239; P=0.0037), colon cancer (aHR, 1.129; 95% CI, 1.029-1.239; P=0.0105), lung cancer (aHR, 1.127; 95% CI, 1.008-1.260; P=0.0353), bladder cancer (aHR, 1.307; 95% CI, 1.071-1.595; P=0.0085), thyroid cancer (aHR, 1.191; 95% CI, 1.085-1.308; P=0.0002), and leukemia (aHR, 1.394; 95% CI, 1.039-1.872; P=0.0270). There was no significant association between the development of secondary malignancy and periodontitis in cancer survivors who were alive 5 years after they were diagnosed with the primary malignancy.ConclusionsPeriodontal disease, including periodontitis, was associated with increased risk of cancer, which persisted after controlling for confounding factors. Further prospective research is warranted to establish a causal relationship.
Is ICI-based therapy better than chemotherapy for metastatic NSCLC patients who develop EGFR-TKI resistance? A real-world investigation
Authors: Cheng Yajie , Yang Bin , Ouyang Wen , Jie Chen , Zhang Wei , Chen Gang , Zhang Junhong , Yu Jing , Xie Conghua 
Published: August 2022

PurposeTo evaluate the outcomes of immune checkpoint inhibitor (ICI)-based treatments versus classical chemotherapy for metastatic non-small cell lung cancer (NSCLC) patients who develop epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance and to explore the population that may benefit from ICI-based therapy.Materials and methodsAll patients who had previously received EGFR-TKI therapy at two cancer centers in China and developed resistance to targeted therapies were included. Progression-free survival (PFS) and overall survival (OS) were utilized to evaluate the outcomes of the study cohort.ResultsA total of 132 patients were included. The median follow-up time for this cohort was 21.7 months (IQR, 14.8–28.8 months), calculated from the date of EGFR-TKI resistance. The median PFS and OS were 4.9 months (IQR, 2.8–9.2) and 13.5 months (IQR, 6.6–26.5 months), respectively. Multivariate analysis showed that ICI-based therapy could significantly improve OS when compared to the classic chemotherapy (hazard ratio [HR], 0.55; 95% CI, 0.34–0.88; P = 0.01) after adjusting for variables such as gender, age, mutation status, and brain or liver metastasis status. The combined modality of ICI plus chemotherapy could offer a long-term OS benefit in most subgroups, such as young (&lt;65 years) patients, and those without secondary T790M mutations or absence of liver and brain metastases, and the populations with good Eastern Cooperative Oncology Group (ECOG) scores.ConclusionFor patients presenting with EGFR-TKI resistance, ICI-based therapy could offer a more favorable survival than classical chemotherapy. The combination of ICI with chemotherapy may be the optimal modality for those with good ECOG PS scores.
Application of a combined radiomics nomogram based on CE-CT in the preoperative prediction of thymomas risk categorization
Authors: Dong Wentao , Xiong Situ , Lei Pinggui , Wang Xiaolian , Liu Hao , Liu Yangchun , Zou Huachun , Fan Bing , Qiu Yingying 
Published: August 2022

ObjectiveThis study aimed to establish a combined radiomics nomogram to preoperatively predict the risk categorization of thymomas by using contrast-enhanced computed tomography (CE-CT) images.Materials and MethodsThe clinical, pathological, and CT data of 110 patients with thymoma (50 patients with low-risk thymomas and 60 patients with high-risk thymomas) collected in our Hospital from July 2017 to March 2022 were retrospectively analyzed. The study subjects were randomly divided into the training set (n = 77) and validation set (n = 33) in a 7:3 ratio. Radiomics features were extracted from the CT images, and the least absolute shrinkage and selection operator (LASSO) algorithm was performed to select 13 representative features. Five models, including logistic regression (LR), support vector machine (SVM), random forest (RF), decision tree (DT), and gradient boosting decision tree (GBDT) were constructed to predict thymoma risks based on these features. A combined radiomics nomogram was further established based on the clinical factors and radiomics scores. The performance of the models was evaluated using receiver operating characteristic (ROC) curve, DeLong tests, and decision curve analysis.ResultsMaximum tumor diameter and boundary were selected to build the clinical factors model. Thirteen features were acquired by LASSO algorithm screening as the optimal features for machine learning model construction. The LR model exhibited the highest AUC value (0.819) among the five machine learning models in the validation set. Furthermore, the radiomics nomogram combining the selected clinical variables and radiomics signature predicted the categorization of thymomas at different risks more effectively (the training set, AUC = 0.923; the validation set, AUC = 0.870). Finally, the calibration curve and DCA were utilized to confirm the clinical value of this combined radiomics nomogram.ConclusionWe demonstrated the clinical diagnostic value of machine learning models based on CT semantic features and the selected clinical variables, providing a non-invasive, appropriate, and accurate method for preoperative prediction of thymomas risk categorization.
Selection of the surgical approach for patients with cStage IA lung squamous cell carcinoma: A population-based propensity score matching analysis
Authors: Shao Shengteng , Song Guisong , Wang Yuanyong , Yi Tengfei , Li Shuo , Chen Fuhui , Li Yang , Liu Xiaotong , Han Bin , Liu Yuhong 
Published: August 2022

BackgroundThis study aimed to conduct a comparative analysis of the survival rates after segmentectomy, wedge resection, or lobectomy in patients with cStage IA lung squamous cell carcinoma (SCC).MethodsWe enrolled 4,316 patients who had cStage IA lung SCC from the Surveillance, Epidemiology, and End Results (SEER) database. The Cox proportional hazards model was conducted to recognize the potential risk factors for overall survival (OS) and lung cancer-specific survival (LCSS). To eliminate potential biases of included patients, the propensity score matching (PSM) method was used. OS and LCSS rates were compared among three groups stratified according to tumor size.ResultsKaplan–Meier analyses revealed no statistical differences in the rates of OS and LCSS between wedge resection (WR) and segmentectomy (SG) groups for patients who had cStage IA cancers. In patients with tumors ≤ 1 cm, LCSS favored lobectomy (Lob) compared to segmentectomy (SG), but a similar survival rate was obtained for wedge resection (WR) and lobectomy (Lob). For patients with tumors sized 1.1 to 2 cm, lobectomy had improved OS and LCSS rates compared to the segmentectomy or wedge resection groups, with the exception of a similar OS rate for lobectomy and segmentectomy. For tumors sized 2.1 to 3 cm, lobectomy had a higher rate of OS or LCSS than wedge resection or segmentectomy, except that lobectomy conferred a similar LCSS rate compared to segmentectomy. Multivariable analyses showed that patients aged ≥75 and tumor sizes of &gt;2 to ≤3 cm were potential risk factors for OS and LCSS, while lobectomy and first malignant primary indicator were considered protective factors. The Cox proportional analysis also confirmed that male patients aged ≥65 to &lt;75 were independent prognostic factors that are indicative of a worse OS rate.ConclusionsThe tumor size can influence the surgical procedure recommended for individuals with cStage IA lung SCC. For patients with tumors ≤1 cm, lobectomy is the recommended approach, and wedge resection or segmentectomy might be an alternative for those who cannot tolerate lobectomy if adequate surgical margin is achievable and enough nodes are sampled. For tumors &gt;1 to ≤3 cm, lobectomy showed better survival outcomes than sublobar resection. Our findings require further validation by randomized controlled trial (RCT) or other evidence.
Effects of Wee1 inhibitor adavosertib on patient-derived high-grade serous ovarian cancer cells are multiple and independent of homologous recombination status
Authors: Roering Pia , Siddiqui Arafat , Heuser Vanina D. , Potdar Swapnil , Mikkonen Piia , Oikkonen Jaana , Li Yilin , Pikkusaari Sanna , Wennerberg Krister , Hynninen Johanna , Grenman Seija , Huhtinen Kaisa , Auranen Annika , Carpén Olli , Kaipio Katja 
Published: August 2022

ObjectiveA major challenge in the treatment of platinum-resistant high-grade serous ovarian cancer (HGSOC) is lack of effective therapies. Much of ongoing research on drug candidates relies on HGSOC cell lines that are poorly documented. The goal of this study was to screen for effective, state-of-the-art drug candidates using primary HGSOC cells. In addition, our aim was to dissect the inhibitory activities of Wee1 inhibitor adavosertib on primary and conventional HGSOC cell lines.MethodsA comprehensive drug sensitivity and resistance testing (DSRT) on 306 drug compounds was performed on three patient-derived genetically unique HGSOC cell lines and two commonly used ovarian cancer cell lines. The effect of adavosertib on the cell lines was tested in several assays, including cell-cycle analysis, apoptosis induction, proliferation, wound healing, DNA damage, and effect on nuclear integrity.ResultsSeveral compounds exerted cytotoxic activity toward all cell lines, when tested in both adherent and spheroid conditions. In further cytotoxicity tests, adavosertib exerted the most consistent cytotoxic activity. Adavosertib affected cell-cycle control in patient-derived and conventional HGSOC cells, inducing G2/M accumulation and reducing cyclin B1 levels. It induced apoptosis and inhibited proliferation and migration in all cell lines. Furthermore, the DNA damage marker γH2AX and the number of abnormal cell nuclei were clearly increased following adavosertib treatment. Based on the homologous recombination (HR) signature and functional HR assays of the cell lines, the effects of adavosertib were independent of the cells' HR status.ConclusionOur study indicates that Wee1 inhibitor adavosertib affects several critical functions related to proliferation, cell cycle and division, apoptosis, and invasion. Importantly, the effects are consistent in all tested cell lines, including primary HGSOC cells, and independent of the HR status of the cells. Wee1 inhibition may thus provide treatment opportunities especially for patients, whose cancer has acquired resistance to platinum-based chemotherapy or PARP inhibitors.
Sirolimus combined with interferon-alpha 2b therapy for giant hepatic epithelioid hemangioendothelioma: a case report
Authors: Liu Xiaolei , Zhou Ruiquan , Si Shuang , Liu Liguo , Yang Shiwei , Han Dongdong , Tan Haidong 
Published: August 2022

Hepatic epithelioid hemangioendothelioma (HEH) is a very rare tumor originated from vascular endothelial cells, with unpredictable malignancy. No standard treatment has been established yet. Although surgical resection and liver transplantation have been reported to be effective treatments with favorable long-term outcomes, the multiple intrahepatic lesions or extrahepatic metastasis makes these procedures unsuitable to most patients. Sirolimus was reported to be an effective drug for epithelioid hemangioendothelioma but only about 10% achieved partial response. Interferon-alpha 2b (IFN-a 2b) has also been used for the treatment of HEH, and the rate of tumor regression was more than 50%. Here, we report a HEH patient with giant intrahepatic tumor (&gt;15cm), who achieved partial response after the combined therapy of sirolimus and IFN-a 2b. The giant intrahepatic lesion (&gt;15 cm) regressed obviously after 8 months treatment and no severe adverse event was reported. The good response and safety of combined therapy with sirolimus and IFN-a 2b provide a promising guidance for future clinical study.
Colon cancer patient with long-term colon stent placement: Case report and literature review
Authors: Huang Qing , Zou Min-hong , Liang Wen-long , Wei Jian-chang , Xie Jie-feng , Li Yong-Qiang , Li Wang-lin , Cao Jie 
Published: August 2022

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer mortality globally. Large bowel obstruction (occurring in 15-30% of patients with CRCs) accounts for approximately 80% of medical emergencies related to CRC. Currently, there is no standard treatment of this condition. The European Society of Gastrointestinal Endoscopy (ESGE) recommends self-expandable metal stent (SEMS) as a bridge (two weeks) to surgery for left-sided obstructing colon cancer. In the present report, we describe an 81-year-old male with colon cancer who underwent colon stent placement for 32 months, but later underwent radical resection. A follow-up of more than four-months revealed that his condition was normal. The history as well as application and advantages of SEMS are discussed in this report.
Clinical relevance of the combined analysis of circulating tumor cells and anti-tumor T-cell immunity in metastatic breast cancer patients
Authors: Muraro Elena , Del Ben Fabio , Turetta Matteo , Cesselli Daniela , Bulfoni Michela , Zamarchi Rita , Rossi Elisabetta , Spazzapan Simon , Dolcetti Riccardo , Steffan Agostino , Brisotto Giulia 
Published: August 2022

BackgroundMetastatic breast cancer (mBC) is a heterogeneous disease with varying responses to treatments and clinical outcomes, still requiring the identification of reliable predictive biomarkers. In this context, liquid biopsy has emerged as a powerful tool to assess in real-time the evolving landscape of cancer, which is both orchestrated by the metastatic process and immune-surveillance mechanisms. Thus, we investigated circulating tumor cells (CTCs) coupled with peripheral T-cell immunity to uncover their potential clinical relevance in mBC.MethodsA cohort of 20 mBC patients was evaluated, before and one month after starting therapy, through the following liquid biopsy approaches: CTCs enumerated by a metabolism-based assay, T-cell responses against tumor-associated antigens (TAA) characterized by interferon-γ enzyme-linked immunosorbent spot (ELISpot), and the T-cell receptor (TCR) repertoire investigated by a targeted next-generation sequencing technique. TCR repertoire features were characterized by the Morisita’s overlap and the Productive Simpson Clonality indexes, and the TCR richness. Differences between groups were calculated by Fisher’s, Mann-Whitney or Kruskal-Wallis test, as appropriate. Prognostic data analysis was estimated by Kaplan-Meier method.ResultsStratifying patients for their prognostic level of 6 CTCs before therapy, TAA specific T-cell responses were detected only in patients with a low CTC level. By analyzing the TCR repertoire, the highest TCR clonality was observed in the case of CTCs under the cut-off and a positive ELISpot response (p=0.03). Whereas, at follow-up, patients showing a good clinical response coupled with a low number of CTCs were characterized by the most elevated TCR clonality (p&lt;0.05). The detection of CTCs≥6 in at least one time-point was associated with a lower TCR clonality (p=0.02). Intriguingly, by combining overall survival analysis with TCR repertoire, we highlighted a potential prognostic role of the TCR clonality measured at follow-up (p=0.03).ConclusionThese data, whether validated in a larger cohort of patients, suggest that the combined analysis of CTCs and circulating anti-tumor T-cell immunity could represent a valuable immune-oncological biomarker for the liquid biopsy field. The clinical application of this promising tool could improve the management of mBC patients, especially in the setting of immunotherapy, a rising approach for BC treatment requiring reliable predictive biomarkers.
Survival benefit of thermal ablation therapy for patients with stage II-III non-small cell lung cancer: A propensity-matched analysis
Authors: Yang Wei-Yu , He Yu , Hu Qikang , Peng Muyun , Zhang Zhe , Xie Shouzhi , Yu Fenglei 
Published: August 2022

BackgroundThermal ablation (TA) is considered a safe alternative to surgical resection for the treatment of non-small cell lung cancer (NSCLC). While previous studies have shown that TA is beneficial for stage I NSCLC patients, however, few have reported on TA efficacy in patients with stage II-III NSCLC. The current study investigated the impact of TA on the overall survival (OS) and cancer-specific survival (CSS) of patients with stage II-III NSCLC.MethodsData on patients with stage II-III NSCLC who did not undergo surgical resection between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM), Kaplan-Meier survival curves, and Cox regression were used for statistical analyses.ResultsA total of 57,959 stage II-III NSCLC patients who did not undergo surgical resection were included in this study, 261 of whom received TA. Overall, TA was associated with a longer OS (p = 0.035) and CSS (p = 0.005) than non-ablation. After 1:3 PSM, 252 patients receiving TA and 732 patients not receiving ablation were enrolled in the matched cohort. The OS (p = 0.047) and CSS (p = 0.029) remained higher in the TA group than in the non-ablation group after PSM. Cox regression analysis showed that age, sex, primary tumor site, pathological type, tumor size, radiotherapy, chemotherapy, and thermal ablation were independently associated with OS and CSS (p &lt;0.05). Subgroup analysis found that the advantages of TA were more pronounced among individuals ≥70 years of age, with tumor size ≤3.0 cm, or who did not receive radiotherapy.ConclusionTA could be an effective alternative treatment for stage II-III NSCLC patients unsuitable for surgical resection, particularly those ≥70 years of age, with tumor size ≤3.0 cm, or who have not received radiotherapy.