bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring C-reactive protein facilitates early discontinuation of immune oncology without compromising outcomes in stage IV non-small cell lung cancer.
Authors: Fugere Tyler , Spradley Ples , Safar Ahmad Mazen 
Published: June 2021

e21107 Background: C-Reactive Protein (CRP) is a non-specific inflammatory marker and reflects tissue destruction seen in metastatic cancer (ca). We have observed a tight correlation with CRP trends mirroring ca activity, hence it may prove to be a valuable marker to monitor response to Immuno-Oncology (IO) in non-small cell lung cancer (NSCLC) patients (pts). Once CRP levels stabilized, IO discontinuation was offered, and consenting pts were closely observed. This strategy resulted in shortened IO duration and impressive treatment-free progression-free survival (tf-PFS). We sought to examine the validity of this strategy using the rate of return to any form of ca therapy within 6 months after stopping IO. Methods: We analyzed all pts of a single provider since 2016 with stage IV NSCLC who had CRP checked while on IO, totaling 23 pts. We excluded pts who stopped IO for reasons besides stable CRP values (5 progressed on IO, 3 died while on IO, 1 had side effects, 1 stopped for a clinical trial, 1 opted to complete 2 years of IO, and 2 are still on IO). Of the remaining 10 patient cohort, all pts were males treated at the VA with ages between 56-75 years at diagnosis. 50% of the cohort had adenocarcinoma and 50% had squamous cell carcinoma. Results: Using the CRP trend to shorten the duration of IO resulted in durable drug-free holidays with none of the cohort returning to any form of ca therapy within 6 months and comparable rates of overall survival (OS) despite shorter IO duration. In KEYNOTE-042, the median OS for pts on the pembrolizumab arm was 16.7 months in the overall population and 20 months in the TPS ≥50% subgroup. Pts were treated for up to 35 months. In our cohort, median OS was 38 months, with all pts currently still alive, and median number of doses of IO was 9 cycles, or approximately 7 months. Our pts had ongoing progression free survival (PFS) after stopping treatment, which we report as tf-PFS. The median tf-PFS of our cohort was 23.5 months. Conclusions: In pts with stage IV NSCLC treated with IO, CRP appears promising as a marker to tailor IO therapy addressing tumor and clinical heterogeneity. Responding pts with stable CRP levels can be safely taken off IO. CRP should be monitored with stable values indicating continued PFS. tf-PFS rather than PFS may serve as a surrogate for cure and carries significant impact for pts financially, socially, and psychologically. [Table: see text]
Efficacy of camrelizumab (SHR-1210) plus apatinib with or without stereotactic body radiotherapy (SBRT) as higher-line therapy for advanced EGFR-mutant non-small cell lung cancer (NSCLC).
Authors: Meng Rui , Wu Lu , Zhang Kai , Zhu KuiKui , Wu Gang , Liu Li 
Published: June 2021

e21128 Background: Despite the dramatic response of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) as first-line treatment for EGFR-mutant NSCLC, the development of resistance is inevitable. The application of third-generation EGFR TKIs is increasing, of which the resistance mechanism is unknow. To date, the optimal strategy has not been defined after failure of EGFR TKIs. Several studies reported the tumor immunogenicity is higher in patients with poor response to EGFR TKIs, suggesting that they may benefit from immunotherapy. Moreover, other studies showed that apatinib (a VEGFR2 TKI) and radiotherapy might augment anti-tumor activity of immunotherapy. In the present study, we reported the efficacy of camrelizumab (an anti-PD-1 antibody) plus apatinib with or without SBRT as higher-line therapy for EGFR-mutant NSCLC. Methods: In this single-arm trial, immunotherapy-naive, NSCLC patients aged 18-75 years, with EGFR-sensitizing mutations, and progression after at least one kind of EGFR TKI were enrolled. All patients received intravenous camrelizumab (200 mg, D1) plus oral apatinib (250mg daily, 5 days on, 2 days off) for a 21-day cycle until disease progression or intolerable toxicity. SBRT (24-30 Gy in three fractions) to at least one metastatic site was completed in some patients. SBRT was decided by the investigator, and patients should have at least one unirradiated lesion to monitor out-of-field response. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall response rate (ORR), and safety. Results: Up to Feb 1, 2021, 24 eligible patients were enrolled. Seven patients were excluded because of treatment discontinuation. Thirteen evaluable patients were included in the efficacy analysis. One had received osimertinib and three had received osimertinib after gefitinib resistance. All patients were previously treated with at least one lines of chemotherapy after EGFR TKI resistance. Eight patients received radiotherapy before enrollment. The median follow-up was 3.5 months (range: 0.7-7.8 months). The median number of cycles was 5 (3-11) PFS and OS data were immature. ORR and disease control rate was 15% (2/13) and 62% (8/13), respectively. Three received SBRT, with ORR of and no disease progression. Conclusions: Camrelizumab plus apatinib with or without SBRT as higher-line therapy showed benefit to patients with EGFR-mutant NSCLC. For patients treated with SBRT, the regimen may have better efficacy. Further investigation is warranted. Clinical trial information: ChiCTR1900028363.
Stereotactic body radiotherapy to the lung primary lesion improves the survival of patients with non-oligometastatic NSCLC harboring EGFR activating mutation with first-line EGFR-TKIs: A real-world study.
Authors: Liu Yongmei , Wei Hao , Zhou Xiaojuan , Yang Hui , Gong Youling , Wang Jin , Xu Yong , Zhou Lin , Xue Jianxin , Wen Zou Bing , Zhang Yan , Zhu Jiang , Peng Feng , Huang Meijuan , Lu You 
Published: June 2021

e21131 Background: This study aimed to explore the clinical value of SBRT for lung primary lesions of EGFR-mutant NSCLC patients with non-oligometastatic disease during first-line EGFR-TKI treatment. Methods: Patients with stage IV EGFR-mutant NSCLC and more than five metastases at diagnosis were identified. All patients were treated with first-line EGFR-TKIs and SBRT for their primary lesions. The primary end points were the progression-free survival-1 (PFS1, time of first TKI dose relative to disease progression based on RECIST), and PFS2 (time of first TKI dose relative to disease progression after SBRT). The secondary endpoints were overall survival (OS) and safety. Results: 79 patients were enrolled, including 45 patients who received SBRT for their primary tumor at the maximal response of EGFR-TKI (the preemptive RT group) and 34 patients who received SBRT for their primary tumor after the occurrence of oligo-progression (the delayed RT group). The preemptive RT group had a significantly better median PFS1 than the delayed RT group (22.3 months vs. 12.9 months, P = 0.0031). The median PFS2 in the preemptive RT and delayed RT groups were 22.3 and 28.9 months, respectively (P = 0.17). The median OS did not differ significantly between the preemptive RT group and the delayed RT group (46.6 versus 51.3 months, P = 0.54). No severe toxicities (≥ grade 3) were recorded. Conclusions: This real-world study showed that preemptive RT to lung primary tumors is a feasible option for patients with EGFR-mutant non-oligometastatic NSCLC who had stable disease during first-line EGFR-TKI treatment, with significantly improved PFS and OS.
Efficacy of various types of chemotherapy for advanced non-small cell lung cancer with EGFR exon 20 in-frame insertions.
Authors: Tang Haibo , Li Xiaoning , Cai Jianhong , Wu Xiaomin , Zheng Yating , Huang Mengli 
Published: June 2021

e21155 Background: Approximately 4% of epidermal growth factor receptor (EGFR)−mutated non-small cell lung cancer (NSCLC) present EGFR exon 20 in-frame insertions. These mutations confer intrinsic resistance to available EGFR tyrosine kinase inhibitors (TKIs), as they result in steric hindrance of the drug-binding pocket. Studies have shown that chemotherapy is superior to currently approved EGFR TKIs as a first-line or second-line treatment for EGFR exon 20 in-frame insertions. Nevertheless, the difference in the efficacy of different chemotherapy regimens in patients with EGFR exon 20 in-frame insertions remains unclear. Methods: Data from advanced NSCLC patients harboring EGFR exon 20 in-frame insertions from an independent cohort (Jenn-Yu Wu, 2019) was used to analyze the objective response rates (ORRs), disease control rates (DCRs), progression-free survival (PFS), and overall survival (OS) of different chemotherapy regimens. Results: Thirty-five advanced NSCLC patients harboring EGFR exon 20 in-frame insertions treated with chemotherapy were used to analyze, of which 7 received gemcitabine plus cisplatin (GC), 22 received pemetrexed plus cisplatin (PC), and 6 received taxol plus cisplatin (TC). ORRs were 31.82% for the patients received PC, 14.29% for GC, and 16.67% for TC. DCRs were 72.73% for the patients received PC, 42.86% for GC, and 16.67% for TC. Median PFS was numerically longer in patients who received PC chemotherapy (6.10 m; 95 % CI: 3.46–8.75) than GC (4.20 m; 95 %CI: 2.40–6.00; P = 0.14) or TC (3.40 m; 95 %CI: 1.96–4.84; P = 0.06). Median OS was significantly longer in patients who received PC chemotherapy (22.20 m; 95 % CI: 8.87–35.53) than GC (9.00 m; 95 %CI: 7.46–10.54; P = 0.04), and numerically longer than patients who received TC (8.10 m; 95 %CI: 0.00–22.62; P = 0.19). Conclusions: These results suggest that pemetrexed plus cisplatin may be the preferred chemotherapy for patients harboring EGFR exon 20 in-frame insertions, but further validation is needed in large clinical studies.
Does order matter? Real-world data on outcomes of successive regimens involving anti-PDx-1 in advanced and metastatic non-small cell lung cancer.
Authors: Hadley David , Gendy Shady 
Published: June 2021

e21159 Background: In 2020, 65% of newly diagnosed advanced (adv)or metastatic (met) NSCLC patients in US started first line (1L) systemic therapy on anti-PDx-1 regimen, 53% of second line (2L). Between broader approvals of anti-PDx-1, increasing use in different therapy lines, and in different regimen combinations, selecting initial and subsequent regimens can be challenging, especially with limited research on outcomes based on order. This analysis uses real-world data to summarize treatment decisions made in a network of oncology centers and relates them to time to second disease progression (PFS2) and overall survival (OS). PRA US medical & prescription claims – 2020 (Jan-Aug). Methods: Deidentified data on adv/met NSCLC patients were selected from Inteliquet’s Cancer Center Research Consortium partners, which comprises academic & community oncology practices as well as integrated delivery networks across the United States. Analysis was limited to patients who started 1L systemic treatment in 2017 & 2018 (index event), progressed and started 2L. Either 1L / 2L / both must have been anti-PDx-1 based regimen. Patients with known actionable driver mutations were excluded. Data from the following 24 months was used to identify regimens and time to progression. PFS2 and OS across the combined 1L and 2L treatment protocols were assessed by proportional hazards regression. The analysis was adjusted for age at diagnosis, gender, PS and treating organization. Results: 132 patients met the study criteria: 53% were female, the median age range at diagnosis was 60-69 years, and 73% were diagnosed with stage IV, and 76% had PS 0-2 at diagnosis. After 24 months, 86% were alive, all had one progression and 44% had a 2nd progression. The most frequently observed treatment patterns are summarized in the table. Conclusions: Same regimens in different order showed different outcomes. There is a significant benefit for both OS & PFS2 by starting with a platinum doublet followed by IO PT, versus the same start followed by IO MT. There is a significant disadvantage in OS by starting with IO MT followed by platinum doublet, versus the reversed order. 1L IO PT versus baseline showed non-significant improvement in PFS2, but not OS.[Table: see text]
Continuous infusion of Endostar combined with chemotherapy in patients with advanced or recurrent mucosal melanoma: A real-world cohort study.
Authors: Liu Xin , Jiang Shiyu , Zhang Xiaowei , Jin Feng , Cao Jun , Meng Yanchun , Xu Yu , Wang Chunmeng , Chen Yong , Yang Huijuan , Kong Yunyi , Luo Zhiguo , Hu Xichun 
Published: June 2021

e21517 Background: Mucosal melanoma is rare and has distinct clinical and genetic features. Even with advances in targeted and immune therapy, the survival of patients with advanced or recurrent mucosal melanomas remains poor. The standard treatment remains controversial and we conducted this real-world study aimed to test continuous intravenous Endostar infusion plus chemotherapy in patients with advanced or recurrent mucosal melanoma in the first-line setting. Methods: In total, all 43 patients with advanced or recurrent mucosal melanoma treated at Fudan University Shanghai Cancer Center between April 2017 and August 2020 were retrospectively included. Patients received dacarbazine plus cisplatin or temozolomide plus cisplatin regimens per the investigators’ preference. Endostar (105 mg/m2) was administered with continuous infusion for 168 hours (Civ 168h). Results: Of the 43 patients, 72.1% had metastatic disease, and 27.9% had locally advanced disease. The most common primary site was the gastrointestinal tract (51.2%), followed by the sinonasal tract (32.6%) and genitourinary tract (14.0%). The most commonly observed mutation was NRAS (23.1%), followed by BRAF (7.7%) and CKIT (5.1%). An objective response was observed in 12 (30.0%) of the 40 evaluable patients, and disease control was achieved in 31 (77.5%) patients. With a median follow-up of 17.6 months, the median progression-free survival (PFS) and overall survival (OS) were 4.9 and 15.3 months, respectively. Multivariate analysis indicated a high lymphocyte-to-monocyte ratio (LMR) was significantly correlated with favorable PFS (p = 0.012, hazard ratio [HR] 0.28, 95% CI: 0.10-0.76). Additionally, a high LMR (p = 0.023, HR 0.29, 95% CI: 0.10-0.84) and BRAF/KIT/RAS mutation (p = 0.028, HR 0.24, 95% CI: 0.07-0.86) were independently correlated with prolonged OS. Toxicity was manageable overall. Conclusions: Continuous Endostar infusion in combination with chemotherapy was effective and safe for the treatment of advanced or recurrent mucosal melanoma. Additionally, a high LMR was correlated with favorable PFS and OS in this patient population.
FAT4 mutation serve as a novel predictor of response to anti-PD-1/PD-L1 treatment in melanoma.
Authors: Zhang Jifa , Chen Dongsheng , Zhang Qin , Duan Qianqian , Yang Qidong , Li Si , Xiao Mingzhe 
Published: June 2021

e21553 Background: FAT4 functions as a tumor suppressor, and previous findings have demonstrated that FAT4 can inhibit the epithelial-to-mesenchymal transition (EMT) and the proliferation of gastric cancer cells. FAT4 is involved in the maintenance of PCP and inhibition of cell proliferation. FAT4 mRNA is repressed in breast cancer and lung cancer due to promoter hypermethylation. FAT4 gene is recurrently mutated in several types. Previous work suggested that FAT4 alterations may enrich for responses to immune checkpoint inhibitors (ICI), validation of function in melanoma is needed. Methods: Using 539-gene target-capture next generation sequencing, we analyzed the FAT4 mutation in 3547 tumor tissue or plasma ctDNA samples (including 122 melanoma) from different patients, and the public database of TACG was also compared. Data from Miao-249 study (n = 151, anti-PD-(L)1/CTLA-4 mono/ combined therapy) was retrieved and analysed. In survival analysis, Kaplan-Meier curves were compared by log-rank test, and the hazard ratio (HR) was determined through a multivariable Cox regression model. Results: In clinical cohort, the frequency of FAT4 mutation in 3547 tumor tissue or plasma ctDNA samples from different patients was 8.11 % (288 in 3547). Meanwhile, the frequency of FAT4 mutation in TCGA cohort was 10.08 % (1105 in 10953). In melanoma datebase, the frequency of FAT4 mutation in 122 melanoma tumor tissue or plasma ctDNA samples from different patients was 5.73 % (7 in 122). Meanwhile, the frequency of FAT4 mutation in melanoma in TCGA cohort was 38.2 % (169 in 422) We further analyzed Kaplan-Meier curves from Miao-249 study (n = 151, anti-PD-(L)1/CTLA-4 mono/ combined therapy). In Miao-249 melanoma cohort, mutation of FAT4 was associated with higher TMB (P = 0.032) and higher mutation count (P = 0.003) in melanoma. FAT4 mutation was associated with prolonged overall survival (OS) compared with FAT4 wt in melanoma (P = 0.0478). Conclusions: In our study, the frequency of FAT4 mutation in pan cancers and melanoma was investigated in clinical and TCGA cohort, which might provide useful information to guide precision medicine. FAT4 mutation may serve as a novel predictor of response to anti-PD-1/PD-L1 treatment in melanoma via upregulating TMB and mutation count.
Transcriptomic profiling of peripheral blood mononuclear cells in patients with multiple primary melanoma.
Authors: Karapetyan Lilit , Yang Xi , Mo Min , Wang Hong , Karunamurthy Arivarasan , Sander Cindy , Storkus Walter , Kirkwood John M. 
Published: June 2021

e21558 Background: Patients (PTs) with cutaneous melanoma (MEL) are at increased risk of developing subsequent MEL. The primary objective of the present study was to determine whether the peripheral blood gene expression profile (GEP) of PTs with multiple primary melanoma (MPM) differs from that of patients with single primary melanoma (SPM) and healthy controls (HCs). A secondary objective is to assess if the peripheral blood immune transcriptional profile varies in relation with clinical and immunopathological characteristics of MEL. Methods: Cases with MPM, SPM and HCs were retrieved from the University of Pittsburgh Human Biological Sample and Nevus Image Banking and Analysis Repository. NanoString PanCancer Immune Profiling of 770-immune related genes was used to define GEP in peripheral blood mononuclear cells (PBMCs). Quality control (QC), data normalization, and differential expression analyses were performed using the ROSALIND Analysis System. Genes with fold change ≥1.5 and p-value < 0.05 were considered as differentially-expressed between cohorts. Results: In total, 47 PTs including 10 with SPM, 40 with MPM, and 10 HCs, were included. GEP data from 3 cases did not meet QC requirements and were discarded. The majority of PTs had stage I/II disease (87.2%). The median Breslow thickness was 1 mm, ulceration was present in 6 (12.2%) MELs. Tumor-infiltrating lymphocytes (TILs) were absent, non-brisk, and brisk in 20%, 65%, 15% of cases, respectively. The expression of IFIT1, MX1, ISG15 was decreased in PTs with MPM in comparison to HCs. In comparison to SPMs, PTs with MPM demonstrated downregulation of B-cell receptor signaling pathway genes (CD19, CD22, CD79A, BLK). 14 genes involved in TNF-alpha effects on cytokine activity, cell motility, and apoptosis, and 12 genes in the IL18 signaling pathway were differentially expressed in PTs with Breslow thickness of >1mm vs ≤1mm. The top downregulated genes in >1mm thick MELs were CD83, VEGFA and CXCL3. Ulcerated MEL had decreased expression of CCL2, CCL3, CCL3L1, CCL4. Stage III MEL had decreased expression of GZMH, MHC Class II genes HLA-DMB, HLA-DRB3, lectin receptor family genes KLRC2 and KLRD1, as well as Type-1 immune-associated biomarkers IRF1, SYK, TBX21 in comparison to Stage I/II cases. Tumors deficient in TILs exhibited decreased expression of Granzyme A and B, T-box 21, and IL18RAP (enhances IL18R-mediated signaling) in peripheral blood. Tumors with brisk TILs had increased expression of the B-cell associated transcripts CD19, CD22, CD79A in peripheral blood. Conclusions: The GEP of PBMC's from PTs with MPM was similar overall to that of PTs with SPM/HC, with only a subset of genes exhibiting differentially expression in PTs with MPM vs. PTs with SPM and HCs. GEP varied in relation to Breslow thickness, stage, ulceration, and TIL content in MELs.
Effectiveness of surface mould brachytherapy in electron era.
Authors: Mehta Jyoti 
Published: June 2021

e21562 Background: In India, skin cancers constitute about 1-2% of all diagnosed cancers.Surgery stays main modality of treatment with adequate surgical margin shown excellent local control rates - generally 95%.However, conditions where surgery is not feasible, brachytherapy is alternative approach.Advanced technology improved the ability to deliver safe and effective radiotherapy, resulting in renewed interest in this modality.Brachytherapy has many advantages: they can deposit a significantly higher dose within a tumor, with better sparing of adjacent normal structures over external beam radiotherapy or electron therapy, which sometimes require irradiating a large volume of tissue in order to provide adequately coverage, which in term increase toxicity. The purpose of our paper is to find out the clinical outcomes of skin tumors and superficial tumours of head and neck region treated with Surface mould brachytherapy (SMB), in terms of survival and toxicity.We report on our institution’s experience with using Co-60 based HDR SMB for the treatment of skin and head and neck superficial malignancies. Methods: A retrospective review of all patients treated with surface mould Co-60-based HDR brachytherapy at our center.A total of 23 patients, with 23 lesions, were treated during this period, and included in the analysis. A total of three of these lesions were treated with a palliative intent, and were included. The most common fractionation scheme was 35 Gy in 10 fractions given daily (52%, n = 12), though a range of doses were used, from 8/2 fractions to 36 Gy/12 fractions. Results: Median age at diagnosis was 52 (range = 28-91). The majority were Squamous cell (43%, n = 10) or Basal cell carcinomas (34%, n = 8). Most lesions were located in the head and neck region. The most commonly used RT dose was 3GyX10 fractions; all patients had individualized CT-based planning.The 5-year overall survival (OS) was 86 %( twenty patients). Three patients were died. Most deaths were from unrelated causes. Response was assessed in OPD 2-4 months post-treatment. Our complete response (CR) rate was 73.9% (seventeen patients), with partial response in three patients; two patients could not be assessed for response and one patient died due to other medical condition. We report a 2-year local control (LC) rate of 91.3%, and local recurrence was found in two patients. The procedure was well tolerated, with no grade 3 or more acute or late toxicities. There was one case of grade 3 ulcer (CTCAE). The 100% isodose line median depth was 0.5 cm, and median surface dose = 126.5%. The median V90 = 92.3%. Conclusions: Surface mould brachytherapy is a safe, effective modality for treatment of skin malignancies or tumors. Brachytherapy was overall well tolerated, with no grade 3-5 acute or late toxicities. This treatment is a good alternative option for those patients unwilling or unable to undergo surgery for their skin malignancies