bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of the multidisciplinary team (MDT) in the management of colorectal cancer (CRC).
Authors: Anghelone Annunziato , Bensi Maria , Barbaro Brunella , Calegari Maria Alessandra , Cina Caterina , Menghi Roberta , Lorenzon Laura , Pozzo Carmelo , Basso Michele , Schietroma Francesco , Valente Giustina , Lococo Filippo , Ardito Francesco , Cellini Francesco , Caira Giulia , Trovato Giovanni , D'Ugo Domenico , Giuliante Felice , Tortora Giampaolo , Salvatore Lisa 
Published: June 2022

e13641 Background: The management of CRC is complex, particularly in metastatic disease, where it is crucial the definition of disease burden, the assessment of radiological response and the identification of the right timing for potential radical surgery or loco-regional treatments. A correct CRC evaluation and the subsequent choice of the most appropriate treatment strategy, need, therefore, a MDT involving surgeons, oncologists, radiologists, radiation oncologists, endoscopists, gastroenterologists and pathologists. Based on such considerations, we investigated the impact of the MDT meeting in the management of CRC at our Institution. Methods: We retrospectively evaluated all the cases discussed at our MDT meeting between September 2019 and September 2021. We collected data, both pre- and post-MDT meeting, regarding radiology evaluation (disease control vs progression), surgical assessment (yes vs no) and radiotherapy evaluation (yes vs no). Primary endpoint was the overall rate of discrepancy in evaluation between pre- and post-MDT meeting. Results: Between September 2019 and September 2021, 696 cases were presented at our MDT meeting. The median age was 65 years (24-86), 391 (56%) patients were male and 553 (79%) patients had metastatic disease at diagnosis. After MDT meeting, a total of 214 decisions were modified, for an overall discrepancy rate of 31%. In particular, among 377 cases discussed for radiology evaluation, 110 decisions (29%) were modified after a central imaging review: 80 cases initially evaluated as progressed disease before MDT meeting were defined stable after MDT meeting, for a discrepancy rate of 73%. Regarding the 246 cases discussed for surgical assessment on primary tumor and/or metastatic sites, treatment strategy changed in 86 cases (35%). More specifically, 16 cases (19%), evaluated unresectable before MDT meeting, were then considered resectable after MDT meeting. Finally, among the 71 cases discussed for radiotherapy evaluation, treatment strategy changed in 18 cases (25%). Conclusions: Our analysis demonstrates a significant rate of discrepancy in radiology and/or surgical evaluation between pre- and post-MDT meeting. Our results show that a MDT allows a considerable modification in CRC management, maximizing the treatment strategy, in particular avoiding unnecessary changes in therapy and allowing surgery where possible.
Clinicians’ perspective on use of immune checkpoint inhibitors and related biomarkers for solid tumors.
Authors: Moser Kaitlynn , Lindpaintner Klaus , Soto Michelle , Geba Daniela , Allen Paul 
Published: June 2022

e13643 Background: Immune checkpoint inhibitors (ICIs) are a valuable treatment option for patients with malignant tumors, but only selected patients respond to ICIs. Available biomarkers are of limited use in guiding ICI therapy. We sought to examine clinicians’ perspective on the use of ICIs and biomarkers for treatment of malignant tumors and to identify unmet needs related to their use. Methods: We conducted in-depth telephone interviews of eight oncologists, and 100 oncologists completed online surveys. Results: Oncologists have a positive attitude toward use of ICIs, and 98% of them prescribe them in all approved indications. Clinicians report that only about half of the patients with solid tumors responded to treatment, overestimating the response rate to ICIs across most types of tumors they treat, compared with data in the literature. They ranked the lack of reliability of biomarkers to guide treatment (rating of 4.4 out of 7) as the top challenge with use of ICIs, followed by lack of overall efficacy and toxicity or occurrence of immune-related adverse events. The biomarkers most often used by survey participants were: a comprehensive panel including driver mutations and tumor mutational burden (69% of respondents), programmed cell death ligand-1 (PD-L1) expression (62%), and microsatellite instability (MSI) (56%). Oncologists indicated that they ordered biomarkers for each type of cancer according to their perceived usefulness of each biomarker in predicting the outcomes for ICI therapy, being more likely to use those perceived as useful or very useful. Conclusions: Clinicians indicate that more reliable therapy-response prediction biomarkers would have a great impact on treatment decisions for patients with solid tumors, reducing unnecessary treatments, side effects, and health care expenditures.
Assessment of telehealth experience among a head and neck oncology population.
Authors: Hung Kin Wai (Tony) , Cracchiolo Jennifer R. , Kim Soo Y , Gillespie Erin F. , Pfister David G. 
Published: June 2022

e13650 Background: Studies suggest that oncology patients are satisfied and sometimes prefer telehealth over an in-person visit; however, data are scarce on when patients find telehealth helpful. Such information would be key in understanding how telehealth can be optimally integrated into cancer care delivery. This study aims to identify factors that influence patient experience of telehealth among a multidisciplinary head and neck oncology population. Methods: From Mar 2020 to Dec 2020, we surveyed head and neck oncology patients at a comprehensive cancer center and 6 satellite sites in New York and New Jersey. We assessed patient experience of telehealth versus in-person visit (primary outcome) and their satisfaction with telehealth (secondary outcome). We conducted multivariate regression to analyze covariates that may influence their experience and satisfaction. Covariates included patient factors (age, gender, race, marital status, primary language, home state, home distance from center, current location at home or clinic), clinical factors (diagnosis, performance status, receiving chemotherapy or radiation), physician factors (profession, current location at main or regional campus), visit factors (type, length, billing level, month, first telehealth visit or not), and a technological factor (device type). Results: Among 1,071 completed surveys (response rate 24.0%), 551 first-unique surveys were analyzed. Surveyed patients were predominantly 60 years or older (64.1%), white (88.3%), married (73.8%), and lived within 50 miles from our cancer center (76.1%). Majority had diagnoses of head and neck cancers (65.7%), followed by thyroid cancers (23.8%), and skin cancers (10.5%). While most patients would recommend telehealth (82.4%), only half reported telehealth the same or better compared to in-person visits (55.7%), whereas the other half reported not as good or unsure (44.3%). In multivariate analyses, patients who found telehealth the same or better than in-person visits were more likely to have thyroid cancers (adjusted odds ratios [aOR]: 2.18, CI 95% 1.44 - 3.36) and have visits from July to December (aOR 1.61, CI 95% 1.14 - 2.27). Satisfaction with telehealth was higher among patients with thyroid cancers (aOR: 2.58, CI 95% 1.20 - 6.41), on visits when patients were at home (aOR 3.48, CI 95% 1.37 - 8.42) and when physicians were on campus (aOR 1.73, CI 95% 1.00 - 2.99). Conclusions: Patient experience with telehealth is diverse among the head and neck oncology population; while one-half found telehealth the same or better compared to in-person visits, the other half found it not as good or unsure. More favorable telehealth experience among patient subgroups highlights the multidisciplinary nature of head and neck oncology and improved acceptance of telehealth over time. Future research to optimize patient experience is needed to ensure successful integration of telehealth in head and neck oncology practices.
Anlotinib in combination with dose-intense temozolomide for the recurrent or progressive glioblastoma after STUPP regimen.
Authors: Yang Qun-ying , Guo Cheng-cheng , Mou Yong-gao 
Published: June 2022

e14014 Background: Nearly all patients (pts) with glioblastoma (GBM) will suffered relapse or disease progression after resection and adjuvant radiotherapy and temozolomide (TMZ). Anlotinib is a new multikinase inhibitors (MKI) blocking angiogenesis and tumor cell proliferation simultaneously and a prospective phase II study was performed to explore the potency of the combination anlotinib and TMZ for pts with relapse or progression GBM. Here, we reports the preliminary results of this study. Methods: This is a prospective, single-arm, open label, phase II study (NCT04547855). Eligible pts were diagnosed with histologically confirmed glioblastoma and experienced relapse or progression for the first time from surgery (including biopsy, partial resection and total resection) and radiotherapy-TMZ therapy (STUPP regimen). Other criteria included 18 to 75 years age, Karnofsky performance status (KPS) ≥ 60% and adequate organ function. The primary endpoint was progression free survival at 6 months (6m-PFS). All pts received orally TMZ (150 mg/m2) from D1-D7 every 2 weeks and anlotinib (12mg, QD) from D1-D14 every 3 weeks until disease progression or unacceptable toxicities. Results: From July 2020 to November 2021, 25 pts were enrolled. The median age was 49 (rang: 23, 62) and the median KPS was 80 (range: 60, 100). Most pts had poor prognostic factors that 17 pts (70.8%) had unmethylated MGMT promoter and 22 pts (91.6%) were IDH wild-type, which 24 pts detected IDH and MGMT status. At the data cutoff date on January 2022, the 6m-PFS was 25.2% and the median PFS was 4.2 months (95% CI, 3.4-5.0m). The median OS reached 9.1 months (95% CI, 8.1-10.2). Tumor response was assessed for all pts. 7 pts achieved partial response and the objective response rate was 28%. 10 pts had stable disease and the disease control rate was 68%. The most common grade 3 or worse adverse events (AEs) was lympyhopenia (48.0%), which may be caused by TMZ. No death was attributed to AEs. Conclusions: Combination of anlotinib and dose-intense temozolomide was tolerable in the treatment of recurrent or progressive glioblastoma. Preliminary results indicated that the efficacy was promising for those miserable pts with worse prognosis factors. Further investigation was ongoing. Clinical trial information: NCT04547855.
Detection of high-grade glioma clusters: Spatial case-control study using EMR data from 2010-2021.
Authors: Aulakh Sonikpreet , Kimble Wesley , Hendricks Brian 
Published: June 2022

e14016 Background: High-grade gliomas (HGGs), like Glioblastomas (GBMs), are the most common malignant intracranial tumors with dismal prognosis. Rural areas have higher HGG related mortality and lesser research advancements. The objective of this study was to identify zip codes with disproportionate risk of HGGs compared to other brain malignancies. Methods: Patients’ electronic health data for this case-control study was extracted from West Virginia University Hospital Systems, 2010-2021. HGG cases were defined using diagnoses codes ICD10-C71 and ICD9-191 (excluding low grade gliomas). The control group was defined by using diagnoses codes ICD10-D32, C79.3, C71 (excluding HGG cases) and ICD9-225.2, 225.4, 198.3, 191 (excluding HGG cases). Controls were exact matched four controls to every case based upon patient five-year age categories and gender. Clustering was assessed globally through difference in Ripley’s-K between cases and controls; and locally using scan statistics. Results: The locations of HGGs and other brain tumors were clustered in the northern and northeastern regions of WV. Global cluster analyses detected statistically significant dispersion of HGG cases compared to our control group. Local cluster analysis identified multi-zip code cluster of HGG patients in northeastern WV between 2010-2021. The average relative risk of HGG compared to other brain malignancies was 1.25, indicating a 25% increase in risk of HGGs compared to other brain cancers within this region. While the local cluster was not statistically significant, the zip code level estimates of relative risk within the cluster ranged from 0.00 to 5.01. This indicated that certain zip codes within the cluster had five times the risk of HGGs compared to non-HGG brain malignancies relative to zip codes outside of the cluster. Conclusions: Findings indicate community level disparities in risk of HGGs relative to other brain malignancies. Additionally, results suggest that HGG cases are seen across the state at a more dispersed pattern than for non-HGG related brain tumors. These overall spatial trends could potentially be attributable to differences in clinical practice, access to care, or social determinants of health throughout WV. Spatial multivariable modeling techniques are needed to identify the specific neighborhood level factors associated with disproportionate patterns of risk identified for WV HGG patients.
A phase II study of anlotinib combined with temozolomide in the treatment of patients with recurrent glioblastoma.
Authors: Xu Qingsheng , Chen Qun , Zheng Xiujue , Cai Jinquan , Zhan Renya 
Published: June 2022

e14021 Background: Glioblastoma (GBM) is a highly vascularized tumor and there are few treatment options after disease recurrence. This study assessed the efficacy and safety of anlotinib, a multitarget tyrosine kinase inhibitor, combined with temozolomide in the treatment of these patients. Methods: This is an open-label, single-arm, phase II trial (ChiCTR2000028957). Patients with histologically confirmed GBM with definite progression after surgery followed by radiotherapy and temozolomide chemotherapy were eligible for inclusion. Additional inclusion criteria were 1) 18-70 years old, 2) KPS≥60, 3) disease progression on MRI as defined by Response Assessment in Neuro-Oncology (RANO) criteria at least 12 weeks (wks) after completion of radiotherapy，4) antiangiogenic therapy naïve. All patients received temozolomide (150-200mg/m2, orally, QD, d1-5/4wks) and anlotinib (10mg, orally, QD, d1-14/3wks) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR, defined as partial and complete responses according to RANO criteria). Safety assessment was done in patients who received at least one dose of study agent. Results: Twenty-one patients (9 males and 12 females) were enrolled between May 2020 and July 2021, and the median age is 55 (range 27-68) years old. Molecular pathological types included MGMT promoter methylated (n = 5), IDH mutation (n = 5), 1p/19q codeletion (n = 8), and TERT promoter mutation (n = 12). Analyses included data collected through December 15, 2021. Tumor response occurred in 17 patients, of which 9 patients had a complete response, and ORR was 81.0% (17/21). There were also 3 patients achieved stable disease and the disease control rate was 95.2% (20/21). Median progression-free survival (PFS) was 13.2 months [95%CI 3.90-22.52], and the PFS at 6 months was 60.0%. The incidence of adverse events of grade 3 was 28.6%, with a higher incidence of elevated AST (25.0%) and ALT (20.0%), hypertension (16.7%), leukopenia (15.4%). No grade 4 or treatment related death occurred in this study through the follow-up. Overall, toxicities are mild and manageable. Conclusions: Anlotinib combined with temozolomide is efficacious and well-tolerated in recurrent GBM patients. Clinical trial information: ChiCTR2000028957.
The analysis of BRAF fusions in Chinese patients with glioma.
Authors: Cheng Chuandong , Ji Ying , Han Tiantian , Guo Didi , Sun Weijie , Lu Guanghua , Bu Fanfeng 
Published: June 2022

e14031 Background: KIAA1549-BRAF fusion is the most common genetic event in pilocytic astrocytoma (PA), and leads to activation of the mitogen activated protein kinase (MAPK) signaling pathway. KIAA1549-BRAF fusion has been considered to be a key variant of PA in WHO CNS5, however, fusions of BRAF with other partner genes leading to MAPK pathway activation, have been described rarely. Herein, we explore BRAF fusions profiles in Chinese glioma patients. Methods: Next generation sequencing of 131-gene profiling was performed to analyze BRAF fusions from 1955 Chinese brain tumor patients in 2019-2021. BRAF fusions were detected by following the standard operating procedure (SOP). We screened out the BRAF fusions, and calculated the mutation frequency and other rare BRAF gene fusions. Results: A total of 49 cases were detected with BRAF fusions, 36 cases were children (< 18 years old), and 13 cases were adults, with a mean age of 13 years (0-57 years). Interestingly, 39(80%) of them were KIAA1549-BRAF fusions, the most common fusion is between KIAA1549 exon 16 and BRAF exon 9 (exon 16–exon 9) followed by (exon 15–exon 9) and (exon 16–exon 11). And the other ten were rare fusions, including DENND2A-BRAF, MRPS33(Intergenic)- BRAF, BCAS1- BRAF, TMEM176B-BRAF, RNF130-BRAF, RIN2-BRAF, GNAI1-BRAF, EXOC4-BRAF, TNK2-BRAF. Most retained BRAF exons 9–18 (7/10, 70%). There was a significant statistical difference in age that the non- KIAA1549-BRAF fusions group was higher than the KIAA1549-BRAF fusions group (25 vs. 10, p < 0.005). Importantly, we identified new BRAF fusion variants resulting in RIN2-BRAF, EXOC4-BRAF, TNK2-BRAF and TMEM176B-BRAF rearrangements, which has not previously been reported in gliomas. Conclusions: We find new BRAF fusions in our 20% glioma patients. In addition, analysis of rare BRAF fusion may help guide diagnosis and develop potential targeted therapies of older PA.
A multi-modal deep learning model integrates clinical, pathomic, and radiomic features for glioma classification and grading.
Authors: Alessio Adam Michael , Khan Sameed , Patel Snehal 
Published: June 2022

e14038 Background: Histopathologic glioma diagnosis relies on the interpretation of the morphologic appearance of tumor cells. This conventional approach suffers from documented inter-pathologist disagreements with minor discordances in 36% and serious discordances in 8.8% of cases (Bruner JM et al. Cancer. 1997). Machine learning applied to automatically extracted pathomic features offers the potential to reduce this inter-reader variability and improve classification accuracy. The addition of clinical history and radiomic features may further improve performance. This work compares the performance of automatic pathomic and radiomic feature analysis to human histologic impressions for glioma classification according to the 2021 WHO scheme. Methods: We developed and evaluated models for predicting the 2021 WHO Glioma class using data from The Cancer Genome Atlas and The Cancer Imaging Archive. We used a cohort of 112 glioma cases with complete data of molecular markers, digital slides, and MRI images. Using molecular markers, we divided this cohort into 2021 WHO types, including 61 glioblastomas, 38 astrocytomas, and 13 oligodendroglioma. We extracted 374 pathomic features summarizing the tumor-rich region on each digital slide. Neural network models were developed with pathomic features alone or in combination with clinical factors (sex, age, and Karnofsky index) and 670 radiomic features obtained from multi-sequence MRI exams. Accuracy was estimated with 5-fold cross validation. Feature importance analysis was carried out with recursive feature elimination to identify the top pathomic and radiomic features related to the specific glioma diagnosis. Results: In this cohort, the conventional histologic impression, reliant on pathologist interpretation, was successful in identifying the WHO glioma class with an accuracy of 0.77 +/- 0.08. The use of pathomics features alone, representing a fully automatic approach, had an accuracy of 0.83 +/- 0.08. The use of pathomics and radiomics information increased the accuracy to 0.88 +/- 0.08. Feature importance analysis revealed that the most important pathomic features were related to nuclear size, nuclear hematoxylin staining intensity, and nuclear circularity. Conclusions: In this pilot study, our machine learning model with pathomic features achieved promising performance for glioma classification. Combining clinical and radiomic features further enhanced performance. We found that the pathomic features that most correlated with the pathologic classification are the same key features that pathologists use in their diagnostic evaluation. While molecular testing is now the definitive reference information for final glioma classification, this pilot study suggests that pathomics analysis could have a valuable role during a pathologist’s initial histologic review.
Clinical characteristics and treatment outcomes in patients with intracranial germ cell tumors: A single center analysis of 1448 patients in China.
Authors: Li Bo , Qiu Xiaoguang 
Published: June 2022

e14048 Background: To explore the clinical characteristics and treatment outcomes of patients with intracranial germ cell tumors (iGCTs). Methods: Clinical data of 1448 patients who were diagnosed with iGCTs based on histology and/or tumor marker elevation between 1990 and 2019 at Beijing Tiantan Hospital were studied retrospectively. Results: The median age was 12 years, and 74.3% of patients were male. In total, 32.6% of patients were of sellar origin, 32.3% were of pineal origin, 20.4% were of basal ganglia (BG) origin, and 14.7% were others. In nonmetastatic germinoma patients, multivariate analysis found that both whole-brain radiotherapy (p < 0.001) and craniospinal irradiation (p = 0.040) could significantly reduce the risk of relapse compared with focal radiotherapy. In nonmetastatic NGGCT patients, the disease control rate was similar among the above three radiation volumes. Among 87 relapsed patients, those with germinoma (n = 35) showed a significantly higher out-field relapse rate than patients with NGGCTs (54.3% vs. 32.7%, p = 0.003). In patients with NGGCTs (n = 52), the in-field (36.5%) and out-field (32.7%) relapse rates were similar. In terms of relapse sites, relapse at the parenchyma (36.4%) was documented only in patients with BG region involvement. In patients with sellar or pineal origin, > 80% of relapses were documented in ventricles and/or the spine. Conclusions: iGCT patients in our series showed unique characteristics. Considering both efficacy and potential adverse effects, the optimal radiation strategy in nonmetastatic germinoma patients should be minimum coverage of at-risk areas. In patients with nonmetastatic NGGCTs, the optimal radiation strategy needs further investigation.