bluuebunny/crossref_metadata_2025 huggingface dataset:
A clinical study of camrelizumab combined with chemotherapy and sequential apatinib in the second-line treatment of patients with advanced non-small cell lung cancer.
Authors: Pan Yueyin , Jiang Fengshou , Du Yingying , Wang Yong , Liu Hu , Wang Zishu , Liang Hui , Bi Minghong , Yao Yiwei
Published: June 2021

e21051

Background: Camrelizumab combined with chemotherapy has shown a higher efficiency and survival benefit in clinical studies of the first-line treatment of lung cancer. This study aims to observe the clinical efficacy and safety of camrelizumab combined with chemotherapy and sequential apatinib in the second-line treatment of patients with advanced non-small cell lung cancer in a real environment. Methods: This is a prospective, open, multi-center observational study that includes advanced lung cancer that is older than 18 years old, regardless of gender, with an ECOG score of 0-1, and recurrence or failure after first-line platinum-based dual-drug chemotherapy patient. Results: As of January 25, 2021, a total of 18 patients were enrolled, of which 12 were female (66.67%), 11 patients had an ECOG PS score of 1 point (61.11%), and 15 patients were stage IV (83.33%), patients, 5 patients with tissue poorly differentiation (27.78%), 55.56% of the patients had undergone immunohistochemical testing, and 66.67% of the patients had become positive for the gene. A history of radiotherapy accounted for 11.11%, and a history of surgery on the primary lesion accounted for 27.78%. Previous first-line chemotherapy options were pemetrexed combined with cisplatin (22.22%), pemetrexed combined with lobaplatin (22.22%), pemetrexed combined with carboplatin (11.11%), bevacizumab combined with Platinum dual-drug regimen (38.89%); Among the 10 patients with evaluable efficacy, 0 had CR, 2 had PR, 6 had SD, and 2 had PD. The ORR reached 20.00% and the DCR reached 80.00%. The overall incidence of adverse reactions is low, and the medication process is safe and controllable. Conclusions: In this second-line clinical study of lung cancer, most of the patients enrolled were patients with poor PS scores and later stages, but the effectiveness and safety of carrelizumab in patients with advanced lung cancer were still confirmed. The dominant population and the combined treatment plan are still being studied. Clinical trial information: ChiCTR2000034597.
Association of LRP1B mutants with immune biomarkers in Chinese non-small cell lung cancer patients.
Authors: Zhang Yi , Guo Taiyan , You Xia , Zhang Qin , Duan Qianqian , Qi Chuang
Published: June 2021

e21060

Background: LRP1B (low-density lipoprotein receptor-related protein 1B) is frequently mutated in non-small cell lung cancer (NSCLC). Previous studies showed LRP1B mutations were associated with prolonged survival in melanoma and NSCLC immunotherapy cohort. Higher tumor mutation burden was found in LRP1B mutated patients, suggesting potential benefit of immunotherapy. Herein, we investigate the relationship of LRP1B and immunotherapy biomarker in lager cohort of Chinese and Western NSCLC patients. Methods: Next-generation sequencing data and clinical data were collected from 1053 TCGA NSCLC patients (Western cohort). A 539-gene panel targeted sequencing assay was performed on FFPE tumor samples from 1056 Chinese pan-cancer patients (Chinese cohort). Both LRP1B mutation ratio and TMB were calculated on the two cohorts following the same criteria. TMB-H was defined as the top quartile of all TMB values. Results: In total, 208 (20%) of the 1056 Chinese patients and 385 (37%) of the 1053 Western patients had at least one mutation of LRP1B genes (LRP1B mutant group). The frequency of LRP1B mutation between Western cohort and Chinese cohort had significant difference (20% vs. 37%, p＜0.001). In both cohorts, TMB was higher in the LRP1B mutant group compared to non-LRP1B mutant group. In Chinese cohort, PD-L1 positive was not associated with LRP1B mutation. Patients with LRP1B mutation were associated with prolonged survival in Western immunotherapy cohort. Conclusions: Our study provided a landscape of LRP1B mutations in a much larger Chinese NSCLC group, which could be a valuable complement to TCGA dataset and previous study. Results of our study was consistent with previous studies. Both in Chinese and Western cohorts, the higher TMB in LRP1B mutant patients suggested potential efficacy from immunotherapy of LRP1B mutant group. This result and the potential predictive value of LRP1B in immunotherapy should be validation in a larger Chinese LRP1B mutant cohort in the further.
The efficacy and safety profile of anlotinib plus docetaxel as second-line treatment in advanced non-small cell lung cancer.
Authors: Xu Zhiqiao , Zhang Yan
Published: June 2021

e21068

Background: Docetaxel is a standard second line treatment in advanced NSCLC, but the treatment effect is limited. Previous studies, such as REVEL, demonstrated that anti angiogenic therapy combined with docetaxel had significantly therapeutic efficacy. Anlotinib is an oral multi target angiogenesis TKI targeting the VEGFR, FGFR, PDGFR and c Kit. The ALTER 0303 trial showed that anlotinib improved both PFS and OS in later-line treatment for advanced NSCLC, and this study aims to investigate the efficacy and safety of Anlotinib combined with docetaxel in second-line treatment in advanced non-small cell lung cancer (NSCLC). Methods: This is a single-center, single-arm clinical trial. A group of 30 patients of histologically or cytologically confirmed, locally advanced stage IIIB-IV NSCLC and with ECOG PS 0-1 were admitted to the Kaifeng Central Hospital Cancer Center. Patients who progressed after first-line treatment were treated with anlotinib (12 mg p.o., QD d1 to 14, q3w) combined with docetaxel (75mg/m2, iv, QD, d1 to 14, q3w) as the second-line therapy. The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: A total of 30 patients were enrolled from October 2018 to April 2020. At data cutoff (Sept. 30, 2020), 30 patients were available for efficacy analysis. The median progression-free survival (mPFS) was 7.5 months (2.0-18.5). Among these patients, there was 1 CR, 9 PR, 15 SD, 5 PD, resulting in the ORR = 33.33% and the DCR = 83.33%. The Cox multivariate analysis showed that stage is an independent risk factor affecting prognosis ( p= 0.003). The most common grade 3 AEs were leukopenia (23,3%), neutropenia (13.3%), hypertension (13.3%), which can be controlled, and no grade 4 or grade 5 AEs occurred. Conclusions: Second line anlotinib plus docetaxel showed clinical benefit in advanced NSCLC patients in terms of PFS, ORR and DCR, and the incidence of adverse reactions are tolerable. This combination might be a promising option for patients advanced NSCLC.
Efficacy of first-line treatments for patients (pts) with advanced EGFR mutated NSCLC: Network meta-analysis of TKI monotherapy and combinations trials.
Authors: Bogdanov Alexey , Moiseenko Fedor Vladimirovich , Zhabina Albina , Volkov Nikita , Artem'eva Elizaveta , Fedyanin Mikhail
Published: June 2021

e21120

Background: Various EGFR TKIs and several combinations are the standard of initial treatment for NSCLC with EGFR mutations. For this moment one size fits all approach is used. Due to the limited nature of this subgroup direct prospective survival comparison of various options is time and resource consuming. The main objective of this study was to compare available prospective trials in a network meta-analysis in order to determine the overall survival (OS) advantage. Methods: Using frequentist approach (netmeta R package) we performed a network meta-analysis of prospective randomized trials comparing having platinum doublet or 1G TKI as a control arm and 1G TKI, 2G TKI, 3G TKI, combination of chemotherapy (CT)+1G TKI, combination anti-VEGF/R+1G TKI as investigation arm in pts with EGFRmut NSCLC. Between trials we compared OS and progression free survival (PFS ) for overall population and subgroups by mutation, sex, age, smoking status. Results: 17 trials involved 4671 pts were considered eligible for meta-analysis. Trials investigated various combinations of TKIs in untreated EGFR mutated NSCLC: 8 had chemotherapy (CT) as control arm (ENSURE, EURTAC, IPASS, NEJ002, OPTIMAL CTONG-0802, WJTOG3405, LUX-Lung-3/6) and 9 with 1G TKIs as control arm (JO25567, NEJ026, 14034 H3E-CR-JIMIT, NEJ009, Noronha et. al, LUX-LUNG7, ARCHER1050, SWOGS1403, FLAURA). Compared to 1G TKIs improved OS was observed for combination of 1G TKI and CT (HR 0.64 (0.53– 0.78)), 3G TKIs (HR 0.80 (0.64-1.00)), 2G TKIs (HR 0.83 (0.72-0.96)) (The OS benefit was ranked No.1 for TKI+chemo (P-score – 0.96), No.2 – 3G TKI (P-score – 0.68), No.3 – 2G TKI (P-score – 0.64)) Addition of anti-VEGF/R therapy did not improve OS (HR 0.91 (0.68-1.21) over 1G TKIs alone. Importantly OS advantage remained significant in a subgroup of ex19del only for 2G TKIs (HR 0.71 (0.53-0.96)). No advantage for particular regimen was seen for L858R subgroup. 3G TKIs (HR 0.46 (0.27-0.78)), combinations with CT (HR 0.55 (0.40-0.75)) and anti-angiogenic agents (HR 0.57 (0.37-0.89), improved PFS over 1GTKIs, while 2G TKIs had a tendency for improving (HR 0.78 (0.58-1.06)). Conclusions: Our network meta-analysis showed that compared to initial treatment with 1G TKI monotherapy - 1G combination with CT, monotherapy with 3G and 2G may provide OS advantage. Still for ex19del subgroup OS benefit was significant only for 2G TKI. The availability of multiple first line options force the importance of stratification of patients for particular treatment type.
Associations between longitudinal pretreatment BMI and neutrophil/lymphocyte ratio(NLR) and progression-free(PFS) and overall survival(OS) in advanced NSCLC patients treated with single agent anti-PD-1/anti-PDL1 monoclonal antibodies(mAbs).
Authors: Randall Megan , Basu Sanjib , Kollipara Revathi , Batus Marta , Bonomi Philip D. , Moudgalya Hita , Borgia Jeffrey Allen , Fidler Mary J.
Published: June 2021

e21189

Background: Several parameters that have been associated with outcomes in patients with metastatic NSCLC treated with anti-PD1/PDL1 mAbs include tumor PD-L1 expression, tumor mutational burden, and baseline NLR. Further investigation into clinical correlates of benefit with immune checkpoint inhibitors remains an unmet need. Methods: The objective of this retrospective study was to examine the potential influence of pretreatment cachexia and chronic inflammation in patients with NSCLC that received second- or third- line single agent anti-PD1/PDL1 mAbs. Weight, BMI, and NLR, as well as longitudinal changes in these variables from at least six-weeks prior to initiation of treatment were correlated with progression-free and overall survival (PFS/OS). These associations were assessed using statistical methods for time-to-event analysis. Results: 192 patients were included: 59% female, 72% Caucasian, 18% African American, 79% current or former smokers. 185 patients had pretreatment NLR values and 63% and 42% had NLR ratios > 3.5 and > 5, respectively. 187 patients had pretreatment weight and BMI available. Of these, 63% had a loss in BMI prior to initiation of anti-PD1/PDL1 mAbs, 29% with > 5% loss. Any BMI loss as well as BMI loss > 5% over the time period prior to treatment initiation were associated with shorter PFS (p < 0.01, 2.1 vs 4.37 mos for loss > 5% vs ≤ 5%) and change in BMI assessed in continuous scale was also associated with PFS (HR = 0.94, p < 0.05). Similarly, any BMI loss and BMI loss > 5% were associated with shorter OS (p < 0.01. 7.33 vs 12.23 mos for loss > 5% vs ≤ 5%) and change in BMI and baseline BMI assessed in continuous scale were additionally associated with OS (HR = 0.97 and 0.94, p < 0.05). Baseline NLR > 5 was associated with shorter PFS (p < 0.01) and baseline NLR assessed in continuous scale was negatively associated (HR = 1.01, p < 0.05). Moreover, pre-treatment NLR > 5 and baseline NLR > 3.5 were associated with shorter OS (p < 0.05). Pre-treatment NLR, baseline NLR, and %change in NLR, assessed in continuous scale, were negatively associated with OS (HR = 1.04, 1.02, 1.12, p < 0.01). Conclusions: This retrospective study identified clinical features of NLR and BMI at treatment initiation and in the immediate pre-treatment period that were associated with PFS and OS on anti-PD1/PDL1 mAbs therapy. These parameters can easily be investigated in the front-line population. They may also have utility in identifying patients that would benefit from therapeutic strategies to reverse weight loss and inhibit immunosuppressive effects associated with elevated NLR in order to increase the effectiveness of immunotherapy.
Mir-34a as predictor of immunotherapy efficacy in NSCLC patients.
Authors: Monastirioti Alexia , Papadaki Chara , Rounis Konstantinos , Kalapanida Despoina , Makrakis Dimitrios , Vardakis Nikolaos , Mavroudis Dimitrios , Agelaki Sofia
Published: June 2021

e21191

Background: MicroRNAs are critical modulators of the immune response and regulate the expression of various immune checkpoints during immunotherapy. In the present study we evaluated the predictive significance of immune related miRNAs in the plasma of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors. Methods: Plasma was obtained from 62 NSCLC patients before the initiation of immunotherapy, administered as second- or third-line treatment. The expression profile of immune-related miR-34a, miR-146a, miR-155, miR-200b, miR-202 and miR-223 was assessed by RT-qPCR. Patients were classified in high and low expression groups according to the median value of each miRNA. Patients that had achieved partial response (PR) or stable disease (SD) were classified as responders, whereas patients with progressive disease (PD) were classified as non-responders. Results: No statistical correlations were observed among miRNA expression and clinical outcomes in the whole group of patients (N = 62). However, in the non-squamous subgroup (N = 36) lower miR-34a expression levels were observed in non-responders compared to responders (80% vs 20%; p = 0.029). Univariate binary logistic regression analysis revealed that only low miR-34a expression (HR: 8.000, 95% CI: 1.215-52.693; p = 0.031) was correlated with the probability of developing progressive disease as best response to immunotherapy. Patients with low miR-34a expression levels were associated with shorter progression free survival (PFS) and overall survival (OS) compared to patients with high 34a expression (1.97 vs 6.33 months; p = 0.042 and 2.93 vs 9,60 months; p = 0.012, respectively). Furthermore, low miR-34a expression emerged as an independent predictor of shorter PFS and OS (HR: 2.449; p = 0.049 and HR: 3.203; p = 0.016, respectively). No other correlations were observed among the rest of the miRNAs and clinical outcomes. Conclusions: Our findings suggest that circulating miR-34a may serve as a potential predictive biomarker in NSCLC patients treated with immunotherapy. These observations need to be further validated in a larger cohort of patients.
Genetic landscape of melanoma in China reveals enrichment of fusions in driver-negative melanoma.
Authors: Lin Xiaohua , Zhang Fan , Liu Jie , Niu Yanling , Wang Chunyang , Li Wei , Ma Tonghui
Published: June 2021

e21577

Background: Melanoma in China has unique characteristics, especially compared with those in euramerican white race. In european and american countries, nearly 90% of melanoma patients are cutaneous melanoma; while 60% of melanoma in China are acral melanoma, accompanied with a considerable proportion of mucosal melanoma. Mapping the mutation landscape of melanoma in China can provide an important basis for targeted therapy of melanoma patients. Methods: Tissue samples from 223 patients with melanoma were sequenced using multi-gene NGS panel Onco PanScan to detect somatic mutations in melanoma. Results: As a result, BRAF (24.2%) and NRAS (15.7%) were the top two most mutated driver genes. In BRAF, V600E was the most common mutation, which accounted for 80% of all BRAF mutations. And Q61R/K was the most common mutation in NRAS, which accounted for 68.6% of all NRAS mutations. As to CNVs, the most frequently amplified genes were CCND1 (23, 10.3%), CDK4 (18, 8.1%), MDM2 (17, 7.6%), FGF19 (16, 7.2%), FGF4 (13, 5.8%), FGF3 (12, 5.4%), KIT (12, 5.4%), RICTOR (12, 5.4%). At the same time, a small number of EGFR, HER2, MET, MYC amplifications were detected. Interestingly, a considerable proportion of CNVs were related with hyperprogressive disease, including amplification of MDM2, CCND1, FGF3, FGF4, FGF19. Except for SNVs and CNVs, 16 gene fusions were detected in 13 samples (5.8%), among which the frequency of fusions involving BRAF, ALK, RAF1 was 2.2% (5/223), 1.3% (3/223) and 1% (2/223) respectively. Among these 16 fusions, only 4 fusions (AGAP3-BRAF, GTF2I-BRAF, TPM3-ALK, DCTN1-ALK) were reported previously, leaving the remaining 12 fusions new detected. As was reported, AGAP3-BRAF fusion was the mechanism by which melanoma patients with BRAF V600E mutations developed resistance to vemurafenib; GTF2I-BRAF fusion mediated the activation of MAPK pathway in fibrous astrocytoma. At last, we also compared the frequency of fusion detected in driver-positive and driver-negative melanoma (no somatic mutations detected in BRAF, HRAS, KRAS, NRAS, NF1, KIT, GNAQ, GNA11), and the result showed the frequency of fusion detected in driver-negative melanoma was significantly higher (9/78, 11.5% vs. 4/145, 2.8%). Conclusions: Through DNA-based NGS, the mutation landscape of Chinese melanoma patients was depicted. BRAF was the most frequently mutated driver gene with the main mutation type of V600E (19.7%) which was significantly lower than that of white race in TCGA-SKCM database (44.2%). On the other hand, DNA-based NGS can detect potentially druggable fusions, and compared with driver positive melanoma patients, fusions were enriched in patients with no driver mutations detected. Perhaps for driver negative melanoma patients, RNA-based NGS should be used to detect more potential druggable fusions which would bring clinical benefit.
The predictive value of MAP2K1/2 mutations for efficiency of immunotherapy in melanoma.
Authors: Ye Ting , Zhang Jieying , Liu Xinyi , Yang Mengmei , Zhou Yuhan , Yuan Siyue , Chen Yaoxu , Gao Chan , Huang Mengli , Ye Chengzhi , Chen Jing
Published: June 2021

e21587

Background: Immunotherapies targeting immune checkpoint receptors have become the cornerstone of systemic treatment options for malignant melanoma. The response to these immunotherapies may correlate with driver mutations. MAP2K1/2 genes are mutated in approximately 10% of melanomas, however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. Methods: Six metastatic melanoma clinical cohorts treated with ICIs were included to investigate the association between clinical efficacy of immunotherapy and MAP2K1/2 mutations. Survival analyses were conducted in cohorts receiving two kinds of ICB agents, namely anti-CTLA-4 or anti-PD-1. RNA expression profiling from these cohorts and from the TCGA melanoma cohort were used to explore the potential mechanism related to immune activation. Results: In an independent anti-CTLA-4-treated cohort (n = 110), we found that MAP2K1/2 mutations are predictive of high objective response rate (17.6% vs 1.3%, p = 0.0185) and long progression-free survival [median OS, 49.2 months vs 8.3 months; hazard ratio (HR) = 0.37; 95% CI, 0.15–0.91; p = 0.0307] and overall survival (median PFS, 19.4 months vs 2.8 months; HR = 0.2; 95% CI, 0.05–0.83; p = 0.0262). This predictive value was further validated in a pooled anti-CTLA-4-treated cohort (n = 235) in terms of overall survival (median OS, 49.3 months vs 22.0 months; HR = 0.44; 95% CI, 0.22–0.91; p = 0.0255). However, no correlation between MAP2K1/2 mutations and overall survival was observed in the anti-PD-1-treated cohort (n = 285). Subgroup Cox regression analysis indicated that MAP2K-mutated patients receive less benefit from the anti-PD-1 monotherapy than from the anti-CTLA-4 treatment (median OS, 27.0 months vs 49.3 months; HR = 3.26; 95% CI, 1.18–9.02; p = 0.0225), which was contrary to the result obtained for the total population. Furthermore, transcriptome profiling analysis revealed that MAP2K-mutated tumors are enriched in CD8+ T cells, B cells, and neutrophil cells and also express high levels of CD33 and IL10, which might be the underlying mechanism for melanoma patients with MAP2K1/2-mutated benefit more from anti-CTLA-4 treatment. Conclusions: We identified mutations in MAP2K1/2 genes as the independent predictive factors for anti-CTLA-4 therapy in melanoma patients and found that anti-CTLA-4 treatment in patient harbouring MAP2K1/2 mutations might be more effective than the anti-PD-1 therapy.
Urinary biomarkers for monitoring treatment response in neuroblastoma patients.
Authors: Amano Hizuru , Hinoki Akinari , Uchida Hiroo , Yokota Kazuki , Ishigaki Takashi , Sakairi Minoru , Abe Mayumi , Takahashi Yoshiyuki , Narita Atsushi , Tainaka Takahisa , Shirota Chiyoe , Sumida Wataru , Makita Satoshi , Takimoto Aitaro , Kano Yoko , Yasui Akihiro , Okamoto Masamune , Nakagawa Yoichi
Published: June 2021

e22008

Background: Neuroblastoma is the most common extracranial solid tumor in children. Its heterogeneity may account for the non-uniform response to therapy; thus, accurate predictive biomarkers are required. We focused on urinary biomarkers since urine contains numerous low molecular weight metabolites that can be used as reliable and non-invasive biomarkers. We detected more than 2,000 metabolites by liquid chromatography-mass spectrometry (LC-MS) through a comprehensive analysis of metabolites in urine samples of patients with neuroblastoma and identified potential urinary biomarker candidates using the Wilcoxon rank-sum test and random forest. In this study, the levels of urinary biomarker candidates were compared between the responder and resistant groups to identify urinary biomarkers for monitoring treatment response. Furthermore, their effectiveness was compared with minimal residual disease (MRD) markers, which are currently considered to predict tumor relapse. Methods: Thirty-two patients with neuroblastoma were divided into two groups according to their responsiveness to therapy: the responder group, in which patients had no recurrence (60 urine samples from 24 patients) and the resistant group in which patients had a recurrence or died (18 urine samples from 8 patients). Levels of urinary metabolites (homovanillic acid [HVA], vanillylmandelic acid [VMA], 3-methoxytyramine sulfate [3-MTS], vanillactic acid [VLA], 3-methoxytyrosine [3-MTR]), and MRD markers (TH, PHOX2B, MK) were compared between the two groups during treatment. Results: The levels of five urinary metabolites (HVA, VMA, VLA, 3-MTR, 3-MTS) were significantly increased in the resistant group compared to that in the responder group. Conclusions: This study shows that three novel urinary metabolites (VLA, 3-MTR, 3-MTS) are significantly associated with the recurrence or death from neuroblastoma.
Noninvasive detection of chromosomal instability in plasma circulating cell-free DNA for early pan-cancer diagnosis using low-pass whole-genome sequencing.
Authors: Lv Ran , Lv Fang , Zhihua Pei , Yu Jianing , Zhao Xiuyu , Liu Yiqian , Zhang Yaxi , Chen Geng , Chen Weizhi , He Ji
Published: June 2021

e22509

Background: Genomic instability is a typical characteristic of the majority of cancers. Early non-invasive detection of cancer is the most effective way of improving the success of treatment and prognosis at present. Traditional tumor screening methods have limitations in terms of selection methods, sensitivity, specificity, cost, and comfortability. Furthermore, although traditional tumor screening is useful for common cancers, there is no available screening test for rare cancers. Here we developed a novel method for cancer detection with Low-Pass Whole Genome Sequencing (WGS) of cell-free DNA (cfDNA). Methods: The cfDNA samples from 52 healthy donors were first used to establish a blacklist of bins. Then the baseline was established to calculate the chromosomal instability score (CINscore). We optimized the parameters of our model using the following discovery datasets: healthy controls (n = 50), breast invasive carcinoma (BRCA) (n = 44), ovarian serous cystadenocarcinoma (OV) (n = 25), colon adenocarcinoma/rectum adenocarcinoma esophageal carcinoma (COREAD) (n = 52), hepatocellular carcinoma (HCC) (n = 43), Gastric adenocarcinoma (GAC) (n = 31); pancreatic adenocarcinoma (PAC) (n = 38), non-small cell lung cancer (NSCLC) (n = 45). Results: We further evaluated the performance of our method using the confirmation datasets of healthy controls (n = 30), BRCA (n = 20), prostate adenocarcinoma (PRAD) (n = 6), OV (n = 7), head and Neck squamous cell carcinoma (HNSC) (n = 10), Uterine Corpus Endometrial Carcinoma (UCEC) (n = 6), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) (n = 5), COREAD (n = 75), HCC (n = 50), GAC (n = 31), cholangiocarcinoma (CHOL) (n = 8), PAC (n = 10), NSCLC (n = 98), esophageal carcinoma (ESCA) (n = 10), and nasopharyngeal carcinoma (NAC) (n = 4). Overall, the area under the curve (AUC) for pan-cancer is 88.7%, and for BRCA, COREAD, HCC, NSCLC, and GAC are 91.7%, 90.0%, 94.5%, 83.4%, and 88.6%, respectively. Moreover, our approach achieved good performance on the the early stage samples of pan-cancer (AUC = 84.3%) as well as COREAD (AUC = 89.3%) and NSCLC (AUC = 79.0%). Conclusions: Collectively, we show that the CINscore inferred from low-pass WGS could be applied in early non-invasive detection of different cancers with high accuracy. Our approach may aid the improvement of the cancer diagnosis.
Impact of medical mistrust (MM) on perceptions of tumor genomic profiling (TGP) among African American (AA) cancer patients: Application of perceptual mapping (PM).
Authors: Hall Michael J. , D'Avanzo Paul , Chertock Yana , Brajuha Jesse A , Bass Sarah Bauerle
Published: June 2021

e22527

Background: TGP is widely used to identify targetable mutations for precision cancer treatment and clinical trials. Many patients have poor understanding of TGP and are unaware of possible secondary hereditary risks. Lack of clarity regarding the relevance of informed consent and genetic counseling further magnify risks for patients. AA patients have lower genetic knowledge and health literacy and higher MM than Caucasian patients, making them especially vulnerable in the clinical setting. Perceptions of TGP in AA cancer patients have not been well-characterized. Methods: 120 AA pts from 1 suburban and 1 urban site (Fox Chase Cancer Center[FCCC] and Temple University Hospital[TUH]) were surveyed. A k-means cluster analysis using a modified MM scale was conducted; chi-square analysis assessed demographic differences. Perceptual mapping (PM)/multidimensional scaling and vector modeling was used to create 3-dimensional maps to study how TGP barriers/facilitators differed by MM group and how message strategies for communicating about TGP may also differ. Results: Data from 112 analyzable patients from FCCC (55%) and TUH (45%) were parsed into less MM (MM-L, n = 42, 37.5%) and more MM (MM-H, n = 70, 72.5%) clusters. MM-L and MM-H clusters were demographically indistinct with no significant associations by sex (p = 0.49), education (p = 0.3), income (p = 0.65), or location (p = 0.43); only age was significant (older = higher MM, p = 0.006). Patients in the MM-H cluster reported higher concerns about TGP, including cost (p < 0.001), insurance discrimination (p < 0.001), privacy breaches (p = 0.001), test performance/accuracy (p = 0.001), secondary gain by providers (p < 0.001) and provider ability to explain results (p = 0.04). Perceptual mapping identified both shared and contrasting barriers between MM clusters (Table). Conclusions: More than 2/3 of AA patients comprised a MM-H cluster. Communication strategies should focus on concerns about family and how to discuss TGP with an oncologist. PM can identify distinct and shared information needs of vulnerable populations undergoing TGP. [Table: see text]
Assessment of solid tumor oncology perception and knowledge gain in internal medicine (IM) residents through oncology video library: Educational intervention in progress.
Authors: Raybould Alison L. , Sorah Jonathan D , Forster Moriah , Powell Jon , Poe Tim , Collichio Frances A.
Published: June 2021

e23000

Background: ACGME and internal surveys performed at the University of North Carolina (UNC) demonstrate that IM residents have historically been dissatisfied with their inpatient oncology experience. Other institutions have demonstrated that a resident oncology video library is feasible and effective in improving clinical knowledge, but formal protected time for module use limited engagement. We created an oncology video library targeted to the resident learner. To enhance impact, we incorporated dedicated time during elective rotations to access the modules. Methods: We performed a pre-survey using a Likert scale to assess resident knowledge perception of solid tumor cancers. We designed a curriculum based on the ABIM blueprint and those cancers frequently encountered on service. We filmed 21 videos of UNC oncologists discussing content they selected for the resident learner. To improve engagement, we provided a half-day of independent study during their outpatient oncology elective. As this study is ongoing, we plan to conduct a post-survey and post-test to evaluate long-term knowledge acquisition. Results: Twenty-seven of the 85 IM residents completed the pre-survey. Eleven (40.8%) reported feeling extremely or somewhat satisfied with inpatient oncology teaching; the remainder felt neutral (29.6%), somewhat (25.9%) or extremely dissatisfied (3.7%). Among oncologic emergencies, most residents felt comfortable managing hypercalcemia (88.9%) and cord compression (55.6%), but not SVC syndrome (29.6%). Prior to implementation of the videos, most reported little/no knowledge gain from their clinical rotations alone across nearly all 20 domains assessed. The only domain in which a majority (65.39%) reported some or significant knowledge gain was chemotherapy toxicities. These domains were selected as video lecture topics. In the five months since their release, each video has been viewed an average 21.5 times. The most viewed video (39 views) was on traditional chemotherapy pharmacology; the least viewed video (9 views) was on pancreas cancer. 28% of residents surveyed reported utilizing the videos, and for those who did access them, half (56.2%) felt that the time for the videos was sufficient, while the other half (43.8%) wished for more dedicated time. Conclusions: IM residents may benefit from an online video library to improve knowledge acquisition and perception of oncology rotations. However, to maximize impact, residents must be given adequate time separate from their service requirements to access the modules. This is a study in progress, and while initial data regarding video utilization appears promising, we await additional information to ascertain knowledge improvement.
A scoping review of oncology medical education interventions in low and middle income countries.
Authors: Karim Safiya , Sunderji Zahra , Jalink Matthew , Mohamed Sahar , Hammad Nazik , Berry Scott R.
Published: June 2021

e23004

Background: A large proportion of the global cancer burden occurs in low and middle income countries (LMICs). One of the significant barriers to adequate cancer control is the lack of an adequately trained oncology workforce. Medical education and training initiatives in oncology are necessary to tackle growing cancer incidence and mortality rates. We performed a scoping review of oncology medical education interventions in LMICs to understand the strategies used to train the global oncology workforce. Methods: We searched OVID MEDLINE and EMBASE databases between January 1, 1995 and March 4, 2020 using a standardized scoping review framework. Articles were eligible if they described an oncology medical education intervention within an LMIC with clear outcomes. Articles were classified based on the target population, the level of medical education, form of collaboration with another institution and if there was an e-learning component to the intervention. Results: Of the 806 articles screened, 25 met criteria and were eligible for analysis. The Middle East/Africa was the most common geographic area of the educational initiative (N=14/25). The majority of interventions were targeted towards physicians (n=15/25) and focused on continuing medical education (n=22/25). Twelve articles described the use of e-learning as part of the intervention. Twenty four articles described some form of collaboration, most commonly with an institution from a high-income country. Language barriers, technology, and lack of physical infrastructure and resources in the LMIC were the most common challenges described. The majority of the initiatives were funded through grants or charitable donations. Conclusions: There is a paucity of published interventions of oncology medical education initiatives in LMICs. Continued medical education initiatives and those targeted towards physicians are most common. There is a lack of collaboration between LMICs in these interventions. Further interventions are needed earlier during medical training and for non-physicians. In addition, increased use of e-learning interventions may overcome certain identified challenges. Encouragement of locally funded initiatives as well as scholarly evaluation and publication of these initiatives are important to improve cancer care in LMICs.
Mutational landscape of Chinese osteosarcoma patients.
Authors: Zheng Shuier , Zhou Chenliang , Qian Guowei , Zhou Yan , Shen Zan , Yin Yan , Mu Tianhao , Huang Tanxiao
Published: June 2021

e23512

Background: Osteosarcoma is the bone tumor which is still incompletely understood. This disease most commonly affects children, adolescents, and young adults. The next-generation sequencing technology is a powerful tool to investigate the genetic basis for this disease. Methods: 12 Chinese patients diagnosed with osteosarcoma were enrolled in this study. The tumor tissue or serial blood sample was collected for each individual and the next-generation sequencing was performed using Haplox 605-gene panel. Mutational landscape was analyzed in the cohort. To explore the biological function of the most frequently mutated genes, GO term and KEGG pathway enrichment analysis were performed. Results: In total, 54 genes related to cancer were detected mutated in these patients. The most frequent alterations were CNKN2A(5/12), CSMD3(3/12), FGFR1(3/12), FGFR3(3/12), FGF4(3/12), TP53(3/12), KRAS(3/12), JAK2(3/12). While CNKN2A works as the stabilizer of the tumor suppressor protein TP53, we found 5 patients were with CNKN2A deletion. Also, there were 3 patients with FGFR1 amplification, 3 patients with TP53 substitution, 3 patients with FGFR3 deletion, and 3 patients with CSMD3 substitution. For FGF4, there were 2 deletions and 1 substitution. For KRAS, there were 2 amplifications and 1 substitution. For JAK2, there were 2 deletions and 1 substitution. The enrichment analysis revealed that positive regulation of biological process, developmental process, and signaling were the most enriched (p < 10-6). Conclusions: Our study explored the most frequently mutated gene in Chinese osteosarcoma patients. Moreover, the enrichment analysis indicated that the genes were enriched in positive regulation of biological process, developmental process, and signaling.
A phase II study of anlotinib in the first-line treatment of locally advanced or metastatic soft tissue sarcoma.
Authors: Huang Xin , Ye Zhaoming , Li Tao , Wei Yongzhong , Wang Shoufeng , Liu Yunxia , Chen Jia
Published: June 2021

e23531

Background: Standard treatment for patients with unresectable locally advanced or metastatic soft-tissue sarcoma is chemotherapy based on anthracyclines, while the tolerance of chemotherapy is limited. We assessed if anlotinib, a multitarget tyrosine kinase inhibitor, is efficacy and safety for the first-line treatment of these patients. Methods: This is an open-label, single-arm, multicenter, phase II clinical trial (NCT03792542) including 44 planned subjects. Eligible patients were aged 18-70 years old, diagnosed with locally advanced or metastatic soft-tissue sarcoma and had at least one measurable lesion according to RECIST 1.1. Other inclusion criteria included ECOG PS 0̃2, chemotherapy and anti-angiogenesis treatment naïve. Patients were administrated 12mg anlotinib once daily for 14 days every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Safety assessment was done in patients who received at least one dose of anlotinib. Here we report the results of a planned interim analysis. Results: From April 2019 to December 2020, 29 patients (16 males and 13 females) were enrolled from 7 hospitals in China. The median age is 57 (range 23-69). Pathological types included liposarcoma (n = 8), undifferentiated pleomorphic sarcoma (n = 5), fibrosarcoma (n = 5), synovial sarcoma (n = 4), and others (n = 7). At the data cutoff date on December 31, 2020, the median duration of treatment was 5.3 months, and the median PFS was not reached. 26 patients were eligible for the evaluation of tumor response.1 achieved partial response (PR) and the objective response rate (ORR) was 3.85% (1/26). 24 had stale disease (SD) and the disease control rate (DCR) was 96.2% (25/26). The clinical benefit rate (CBR), defined as the proportion of patients who achieved durable disease control (CR/PR/SD) more than 4 and 6 months, were 65.4% (17/26) and 38.5% (10/26) respectively. Most adverse events (AE) were grade 1 or 2. The most common grade 3 AE was hypertension (17.2%). No grade 4 AEs or treatment related death occurred in this study through the last follow-up. Conclusions: This interim analysis showed anlotinib of promising efficacy and favorable tolerance in the first-line treatment of locally advanced or metastatic soft- tissue sarcoma. Clinical trial information: NCT03792542.
Antibiotic use during end of life in patients with advanced malignancy: A retrospective analysis.
Authors: Poojary Shamali , Deodhar Jayita , Chodankar Akanksha , Damani Anuja , Ghoshal Arunangshu , Muckaden Mary Ann
Published: June 2021

e24002

Background: Patients with advanced malignancy have complex symptoms towards end of life. Some of these symptoms include febrile illness and infections. Benefits of treating infection and fever with antibiotics should be weighed out with goals of care for these patients. This study aims to understand the frequency of use of antibiotics and its association with symptom control in the last two weeks of life in advanced cancer patients on best supportive care. Methods: This is an observational retrospective analysis of medical records maintained for advanced cancer patients who have been enrolled in home-based palliative care services. 8 months data was analyzed. Sociodemographic variables, cancer diagnoses, symptoms, use and type of antibiotics prescribed were noted. Relevant statistical analysis was done using IBM SPSS v 25. Results: Of 256 patients included in the analysis, 133 (52%) were male. 57 (22.3% ) patients had gastrointestinal (GI) cancer and 45 ( 17.6%) had lung cancer. 175 (68.4)% died at home and 50 (19.5%) in hospital. 9 (3.1 %) patients had fever. 10 (3.9%) patient had respiratory, and 18 (7%) had gastrointestinal symptoms, respectively. Other symptoms noted were wound infection (10,3.9%), skin and soft tissue (5,2%). Other symptoms noted were wound infection (10,3.9%), skin and soft tissue (5,2%). Only 2 patients had urinary tract symptom. 49 (19.1%) patients had received antibiotics in their last two weeks of life. Intravenous (IV) route of administration was slightly higher than oral (28 vs 21 patients).More than half the patients received 2 antibiotics. Amoxicillin/clavulanate was the most common oral antibiotic and Cefoperazone/ sulbactam was the most common IV antibiotic. Symptom relief was noted in 9 patients (18.4%) however it was statistically significant (p<0.001). Conclusions: Of 256 patients included in the study, 19% had received antibiotics in last two week of their life. Use of intravenous route for antibiotic administration was more than oral route. Gastrointestinal and respiratory symptoms were common cause for antibiotic prescription. Symptomatic benefit was noted with antibiotics use in these patients. Judicious use of antibiotics during end of life care should be considered.
Chemotherapy at the end of life: Do we know when to stop?
Authors: Barak Renana , Zagagi Yohay Einav , Waissengrin Barliz , Wolf Ido
Published: June 2021

e24005

Background: Aggressive end-of-life (EOL) care in cancer patients, especially the administration of chemotherapy, is considered a poor-quality measure, that may divert the treatment course from its' main palliative intent. Decisions taken at EOL are more than evidence-based and often rely on cultural and personal prospects. The universal and free Israeli health care system enables the administration of active treatment without financial or regulatory barriers, even at EOL. Two major advancements in recent years were the implementation of national at-home palliative care services and the approval of targeted and immunotherapies for advanced cancers. We hypothesized that these changes will reduce the use of chemotherapy at EOL. Methods: We sampled consecutive patients treated at a tertiary oncology center who died of advanced cancers between January 2019 to August 2020, and examined the administration of oncologic treatments near EOL. Results: A total of 294 patients were included. Their median age was 67 and 147 were men, 64% (189) of the patients received oncologic treatment during the last month before death, chemotherapy was administered in nearly two-thirds of the cases, 64% (121), followed by immunotherapy (21%, 40), targeted therapy (10%, 19) and a clinical trial (5%, 9). Neither age (P = 0.4), gender (P = 0.9), performance status (P = 0.8), disease duration (P = 0.5), and type of previous oncologic treatment (P = 0.3) were associated with aggressive EOL care. Conclusions: Our data demonstrate that in the absence of any regulatory or financial limitations, an aggressive EOL care may be administered to the majority of patients, regardless of age, performance status or disease duration. Despite increasing use of immunotherapy and targeted therapies and despite its’ toxicity profile and low beneficial effect at this stage, chemotherapy remained the most commonly used type of treatment. These data call for the implementation of educational measures and appropriate universal guidelines, aiming at improving quality of treatment at the EOL, focusing on quality of life rather than the elusive potential of extending life.
Evaluation of comprehensive geriatric assessment impact in oncological decision-making process.
Authors: Ejarque Clara , Villace Gallego Pablo , Andreu Pablo , Soriano Sandra , Rodríguez Marta , Medina Laura , Bonfill Teresa , Joaquin Julia Giner , Fernandez Paula Ribera , Macias Declara Ismael , Vilà Laia , Gallardo Diaz Enrique , Seguí-Palmer Miguel Angel
Published: June 2021

e24020

Background: Elderly patients (pts) diagnosed with cancer may present frailty conditions at baseline that could have a direct impact on tolerance and toxicity of oncological treatments (ttm). Comprehensive geriatric assessment (CGA) is considered a useful tool in the approach of these pts. CGA allows assessing functional reserve and potentially treatable comorbidities, leading to pt classification into 3 categories (fit, medium fit, unfit) before ttm decision. We evaluated the implantation of a CGA program in our center and its impact on ttm-decision and ttm-related toxicities. Furthermore, we evaluated survival outcomes. Methods: Retrospective, observational, single-institution analysis between 2017-2020. Pts ≥70 years with a cancer diagnosis and suspected frailty were evaluated by Oncogeriatry division before ttm decision. Pt characteristics at baseline (functional status [st], cognitive st, nutritional st, and comorbidity) were recorded. IBM SPSS Statistics software was used for statistical analysis. Variance analysis was calculated with Kolmogorov-Smirnov. Survival was calculated with Kaplan-Meier. Results: 147 pts were included (median [m] age 83 years). Referred pts presented good functional st (mBarthel Index 95), cognitive st (mMMSE 28, mMiniCog 3), and nutritional st (m abbreviated MNA13), and low comorbidity (mCharlson Index 1). After CGA, 49% pts were classified as fit, 28.6% as medium fit, and 22.4% as unfit. 71.4% pts received cancer-specific ttm (fit 91.6%, medium-fit 78.5%, unfit 18%). The correlation index between the initial ttm proposal and final ttm performed after CGA was 56.4% (76% in fit, 57.1% in medium-fit, and 12% in unfit). 18.4% of pts had ttm-related complications. 74 pts died during follow-up (34.7% fit, 59.5% medium fit, 72.7% unfit). 35.4% of deaths were related to cancer and 10.9% to comorbidity. Only 4 deaths were related to ttm. The median survival was 29 months (mo) in fit, 12.8 mo in medium-fit, and 8.5 mo in unfit pts. Conclusions: The majority of pts had preserved cognitive functions and low comorbidity, and were independent for daily-life activities. After CGA, almost 50% pts had modifications in their initial treatment strategy (higher rates in medium fit and unfit). Most fit pts received standard oncospecific ttm and had higher survival rates compared to unfit pts. These results show the relevance of geriatric approach in elderly cancer pts, which allows a personalized ttm.
Impact of adding plinabulin to pegfilgrastim for the prevention of TAC chemotherapy (Chemo) induced neutropenia (CIN), on patient quality of life (QoL).
Authors: Mohanlal Ramon , Lelorier Yvette , Mitchell Dominic , Huang Lan , Blayney Douglas W.
Published: June 2021

e24031

Background: Plinabulin is a novel non-G-CSF small molecule being developed for the prevention of chemotherapy in conjunction with pegfilgrastim and is administered via 30 min IV infusion, 30 min after chemo on Day (D) 1. The QoL was analyzed using the Functional Assessment of Cancer Therapy - General questionnaire (FACT-G) as part of a phase 3 (Ph3) clinical trial comparing pegfilgrastim alone versus pegfilgrastim and plinabulin for the prevention of neutropenia in newly diagnosed breast cancer patients being treated with Docetaxel (75 mg/m2), Doxorubicin (50 mg/m2), and Cyclophosphamide (500 mg/m2) (TAC) on D1 for four 21 D cycles and study treatment. Methods: The FACT-G was administered to patients in China and Ukraine using an ePRO app downloaded onto patients' phones as part of the Phase 3 PROTECTIVE-2 trial (NCT0329457) with TAC. Patients completed the FACT-G during each chemo cycle at D-1, D1, D8 and D15. Patients received reminders 1 hour before the required completion time and all entries were time stamped. The FACT-G measured the impact of cancer on four categories: Physical wellbeing, Social wellbeing, Emotional wellbeing and Functional wellbeing. Results: Compared to pegfilgrastim alone, patients on plinabulin + pegfilgrastim performed significantly better for Physical wellbeing on D8 and D15 of Cycle 2 (p < 0.0589 and p < 0.0039 respectively) and Cycle 3 (p < 0.0360 and p < 0.0343 respectively). Further analysis of the sub questions showed that both energy levels “I have a lack of energy” and pain”(I have pain” were significantly better for the plinabulin + pegfilgrastim combination versus pegfilgrastim alone (p < 0.0377 and p < 0.0420 respectively). Overall FACT-G completion compliance for the trial was 91%. Conclusions: The Physical wellbeing (in particular, pain and for energy levels) of patients receiving plinabulin in combination with pegfilgrastim for the prevention of TAC CIN, was significantly less impacted by chemo dosing compared to the pegfilgrastim alone arm. In addition, the results suggest that patients receiving the combination therapy recovered their pre-chemo Physical wellbeing levels more rapidly. Clinical trial information: NCT03531099.