bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of COVID-19 on the survival outcome of lung cancer at a Canadian academic centre: A real-world data analysis.
Authors: Agulnik Jason S. , Kasymjanova Goulnar , Pepe Carmela , Friedmann Jennifer , Small David I. , Sakr Lama , Wang Hangjun , Spatz Alan , Cohen Victor 
Published: June 2023

e21200 Background: The Covid-19 pandemic directly affected the screening, diagnosis, and treatment of lung cancer patients. Our group recently reported that the rate of new lung cancer diagnoses declined during the first year and significantly increased during the second of COVID-19 pandemic. The effect of COVID-19 on lung cancer treatment outcomes in literature is still limited and mostly reported either as predictive survival using prioritization and modeling techniques. In this study, we aimed to quantify the effect of COVID-19 on lung cancer survival using real world data collected at the Jewish General Hospital, Montreal. Methods: This is a retrospective chart review study including patients diagnosed with lung cancer between March 2019 and March 2022. We compared 3 cohorts: Cohort1: 2019 (pre-COVID) Cohort2: 2020 (1st year of COVID) Cohort3: 2021 (2nd year of COVID). Results: A total of 417 patients were diagnosed and treated with lung cancer at our centre throughout the three-year study: 130 in 2019, 103 in 2020 and 184 in 2021. Although the proportion of advanced/metastatic stage lung cancer remained the same for the three cohorts, there was a significant increase in the late-stage presentation during the pandemic. The proportion of M1c (multiple extrathoracic sites) cases in Cohorts 2 and 3 was 57% and 51% respectively compared to 31% in cohort 1 (p < 0.05). Median survival for early and locally advanced stages of lung cancer was similar in the 3 cohorts. However, the subgroup of patients diagnosed in the advanced/metastatic stage had a significantly increased risk of death during the pandemic (cohorts 2 and 3). The 6-month mortality rate was 53% in 2021 compared to 47% in 2020 and 29% in 2019 (p = 0.004). The median survival in this subgroup of patients decreased significantly from 13 months in 2019 to 6 months in 2020 and 5 months in 2021 (Table 1). Conclusions: The present study represents the impacts of the COVID-19 on lung cancer survival outcome. The COVID-19 pandemic potentially caused the significant shift to M1c stage and contributed to an increase 6 month mortality rate and poorer overall survival in the advanced/metastatic lung cancer patients diagnosed and treated during the pandemic.[Table: see text]
Liquid and tissue profiling of somatic mutational landscape of non-small cell lung cancer from an Indian cohort.
Authors: Limaye Sewanti Atul , Disel Umut , Plowman Nick , Rohatgi Nitesh , Syed Nelofer , Limited Datar , Datta Vineet , Patil Darshana , Raut Nirmal Vivek , Raja Dr T , Kurzrock Razelle 
Published: June 2023

e21202 Background: Circulating tumor DNA (ctDNA) encompasses spatial and temporal heterogeneity, tumor evolution, and is ideal for repeat sampling and predictive therapeutic course corrections whereas tissue is the first choice for molecular profiling. We report the mutational landscape of an Indian NSCLC cohort, with focus on liquid biopsy and value addition offered by paired tissue and liquid profiling. Methods: The study comprised 507 tumor tissue and 1271 liquid biopsies from NSCLC patients. Evaluation of single nucleotide alterations, copy number alterations and fusions was conducted using targeted next generation sequencing with paired tissue and liquid profiling in a sub cohort (n = 45). Results: In tissue based analysis (n = 507), EGFR-sensitizing mutations were the most common alterations, detected in 41.4% of samples. Among these, Exon 19 deletion was seen in 46.3%, Exon 21 L858R in 23.9%, Exon 20 insertion in 4.6%, Exon 18 G719X in 3.7% and compound mutations in 5%. TP53, KRAS and PIK3CA mutations were detected in 34.5%,13.4% and 6.3% respectively. MYC was commonly amplified (15.4%) gene followed by PIK3CA (4.1%), CCNE1 (3.3%), EGFR (2.9%), and MET (2.9%) amplifications. Tissue fusion analysis (n = 398) detected ALK in 6.3%, ROS1 in 3.3%, and RET in 1.8%. METEx14 was detected in 4.5%. Liquid biopsy (n = 1271) showed comparable mutation spectrum as tissue, with the EGFR gene being the most altered (32.9%). Mutations in TP53 were observed in 26.4%, KRAS in 7.4%, PIK3CA in 4.4% and BRAF in 3%. In EGFR positive individuals, EGFR T790M was detected at higher frequency in liquid (16.7%) than tissue (8.6%), indicating this acquired resistance alteration being better captured in liquid biopsy than tissue due to tumor heterogeneity and tumor evolution. 2 liquid biopsy samples identified additional KRAS driver mutations not seen in the paired tissue analysis, highlighting the utility of simultaneous tissue and liquid analysis. Concurrent actionable alterations were detected in 11% of tissue and 5% of liquid samples. Conclusions: We report the largest liquid biopsy study reporting the genomic landscape from NSCLC cases of Indian origin along with tissue based molecular landscape. Presence of alterations like KRAS and EGFR T790M in liquid but absence in concurrent tissue biopsy shows utility of paired tissue and liquid biopsy profiling. Higher incidence of targetable and co-existing alterations in the Indian population highlight the utility of broad molecular profiling for successful utilization of targeted therapies. [Table: see text]
Class II and class III BRAF mutations in patients with advanced non-small cell lung cancer (NSCLC): Clinical characteristics, mutation patterns, and survival outcomes.
Authors: Rasokat Anna , Kron Anna , Nogova Lucia , Siebolts Udo , Scharpenseel Heather , Riedel Richard , Michels Sebastian Yves Friedrich , Fischer Rieke Nila , Eisert Anna , Prang Darinka , Beckers Frank , Kambartel Kato , Kaminsky Britta , Schaaf Bernhard , Schulte Wolfgang , Serke Monika Heidi , Merkelbach-Bruse Sabine , Buettner Reinhard , Wolf Juergen , Scheffler Matthias 
Published: June 2023

e21204 Background: Class II and class III BRAF mutations (i. e., non-V600X) in NSCLC differ from V600E in terms of dimerization and KRAS-dependency. Whereas V600X is effectively targetable by combined BRAF- and MEK-inhibition, no specific targeted approach for non-V600X exists, and a comprehensive description of the patient group is lacking. This retrospective cohort analysis presents clinical and genomic characteristics of a large cohort of patients with advanced BRAF nonV600X mutant lung cancer. Methods: Molecular data of 1411 lung cancer patients staged IIIb/IV and harboring BRAF mutations were linked to hospital registry data in the NGM (Network Genomic Medicine) database. Biospecimens were analyzed using next-generation sequencing (NGS). Results: 721 patients with BRAF non-V600X mutations were identified, of whom 10.5% had been diagnosed with squamous cell carcinoma (SCC) and 89.5% had non-squamous histology. Median age at diagnosis was 66 years (range: 34-81) and the cohort comprised 409 (56.7%) men and 312 (43.3%) women. 301 (41.8%) of the BRAF non-V600X alterations detected in this cohort are “activators” in the MAPK pathway (class II, including G469A/V/R, G464A/E/L/V, K601E/N, L597Q/R/V), while 310 (43.0%) function as “amplifiers” (class III, including mutants such as D594A/G/H/N, G466A/E/V, G469E, N581I/S/T in this cohort). While 21.5 % (155; SCC: 12.3%; non-SCC: 22.9%) of patients did not have any co-occurring mutations (55.6% of SCC and 37.1% of non-SCC patients respectively), TP53 was the most frequent co-mutation, detected in 56.6% (SCC: 74.0%; non-SCC: 53.8%) of patients. 16.4% (118) exhibited a KRAS co-mutation (SCC: 4; non-SCC: 109). A preliminary survival analysis suggests no significant difference in overall survival between these broad classes (HR 0.92, 95%-CI 0.62, 1.36). Conclusions: The study highlights the heterogeneity of patients with BRAF class II and class III regarding histology and co-mutational status, with both classes equally frequent. A more granular investigation of non-V600X alterations and their associated clinical outcomes under different treatment approaches is ongoing.
Patterns of actionable biomarker testing in lung cancer patients: Disparity or an opportunity for improvement.
Authors: Horn Robert Asa , Pawar Dushyant , Bharathidasan Kavya , Sekhon Jasmine Kaur , Rehman Shabnam 
Published: June 2023

e21211 Background: In 2018, lung cancer represented about 13% of new cancer diagnosis but was still the leading cause of cancer deaths at 25%. In the last five years, rates of new cases of lung cancer have decreased by 11% and survival has increased 21% nationally; largely due to advancements in screening, diagnosis and expanding treatment modalities, including targeted therapies geared toward specific molecular alterations. Despite these advancements, there are still shortcomings in terms of next generation sequencing (NGS) utilization for detection of molecular aberrations. A recent query of 37,925 patients with stage IV non-small cell lung cancer (NSCLC), diagnosed between 2010 and 2018 discovered that only 22% of all patients had any molecular testing. Only 3% of these patients received any form of targeted therapy. This further illustrates the ongoing gap between molecular diagnostics and its clinical utilization. Methods: Our project serves to assess this shortcoming in our patient population. In this retrospective chart review and quality improvement project, the goal was to identify the limitations that led to delays or omittance of timely NGS in patients with newly diagnosed NSCLC. Under an IRB approval, a system was created where once a biopsy was confirmed to be NSCLC, tissue was sent for NGS. Prior to this intervention, molecular testing had to be ordered by an Oncologist after the patient was seen in clinic, generally during their first outpatient appointment or when discussed in multidisciplinary meetings. Additionally, testing was shifted from individual molecular studies, which would frequently exhaust tissue sample, to only comprehensive panels. Results: The charts of 194 patients with newly diagnosed NSCLC between 2014 and 2022 were analyzed. Of these patients, 125 patients (64.4%) had completion of at least one molecular test. 36 patients (18.6%) had only been tested for programmed death-ligand 1 (PDL1) and 33 patients (17.0%) had no immunohistochemical or molecular testing following biopsy results. The time from biopsy to completion of molecular testing was compared to 34 patients following implementation of our protocol. The median time from biopsy to availability of results was 29 days before our intervention and decreased to 23 days afterwards. Additionally, molecular testing increased to 100% in our newly diagnosed NSCLC patient population. Conclusions: As the genomic revolution continues and the importance of targeted therapy for NSCLC in both the adjuvant and metastatic setting progresses, timely next generation sequencing will be paramount for optimal treatment selection. Our project shows that through the implementation of systems codeveloped between medical oncology and anatomic pathology, turnaround times of molecular testing can be greatly improved and widely implemented.
Oncomine Dx Express CE-IVD liquid biopsy assay for non-small cell lung cancer: Performance review and analytical validation.
Authors: Schageman Jeoffrey 
Published: June 2023

e21218 Background: Clinical diagnostics assays for oncology are becoming more readily available due to the advancement and democratization of Next-Generation Sequencing (NGS). Additionally, liquid biopsy can be used in NGS to detect genetic variants in circulating tumor DNA and RNA. Liquid biopsy is a less invasive option compared to traditional biopsy methods for early detection and continuous monitoring of cancer treatment outcomes. Here, we discuss screening of over 3,500 non-small cell lung cancer (NSCLC) samples, and the analytical validation of the Oncomine Dx Express Test (ODxET) and Genexus Dx Integrated Sequencer for detection of clinically significant variants in liquid biopsy samples. Methods: Our team screened over 3,500 NSCLC liquid biopsy samples in search of high priority clinical variants. Variants selected for analytical validation studies included ERBB2 exon 20 insertion, EGFR exon 20 insertion, EGFR exon 19 deletion, EGFR T790M, KRAS G12C, BRAF V600E, and RNA fusion isoforms including ALK, NTRK1/2/3, RET, and ROS1 oncogenic drivers. Over 550 screened samples were found to be positive for these variants of interest. This screening was performed on the Genexus Dx Integrated Sequencer according to the user guide. Results: The Genexus Dx Integrated Sequencer automates library preparation, sequencing, analysis, and reporting QC metrics and variant calls. Sequencing run setup is quick and straightforward, taking less than 15 minutes to start a run and just over 24 hours to go from nucleic acid to report. Limit of detection (LoD) for DNA SNVs, insertions, and deletions at 5 ng DNA input level ranged from 0.65% to 1.82% allelic frequency (AF), depending on the variant. The higher DNA input of 30 ng resulted in a lower LoD range, from 0.31% to 0.42% AF. RNA fusion and splice variant LoD at 5 ng sample input ranged from 9.9 to 19.6 molecular counts. The higher 30 ng input resulted in a lower LoD range for RNA variants as well, ranging from 6.4 to 8.0 molecular counts. In the analytical accuracy study, the false positive rate was found to be 0.2% for SNVs, 0% for insertions/deletions, and 0% for fusion targets. In the analytical reproducibility study, the average with-in run repeatability call rate (No Calls excluded) was 99.64% for DNA variants and 98.75% for RNA variants. Conclusions: Here, we demonstrated that the ODxET workflow on Genexus Dx Integrated Sequencer is a fast and efficient tool for testing clinical NSCLC liquid biopsy samples with high sensitivity and specificity.
Association of immune-related adverse events and improved treatment outcomes across race/ethnicity in a diverse patient population.
Authors: Jani Chinmay , Radwan Amr , Al Omari Omar , Patel Mohini , Burns Laura , Mackay Zoe , Li Liuping , Mahdaviani Kiana , Weinberg Janice , Everett Peter C. , Suzuki Kei , Mak Kimberley , Kulke Matthew H. , Tapan Umit 
Published: June 2023

e21220 Background: The development of immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICIs) has been associated with improved clinical outcomes in advanced non-small cell lung cancer (NSCLC). However, how this association extends across race and ethnicity remains uncertain. In this study, we evaluated the association between the development of irAEs and treatment outcomes across different racial and ethnic groups treated at a single institution. Methods: We performed a retrospective chart review to identify irAEs and treatment outcomes in patients with advanced NSCLC who had received treatment with ICIs at our institution between 2015-2020. The incidence of irAEs across racial subgroups was compared using logistic regression analysis. Cox regression analysis was carried out to evaluate the associations between the development of irAEs and treatment outcomes [Overall Survival (OS) and Progression Free Survival (PFS)] in these subgroups. Results: We identified a total of 138 NSCLC patients who received treatment with ICIs, of whom 50% (69) identified as non-Hispanic Black (NHB) and 50% (69) as others, including 34% (47) as non-Hispanic White. The overall incidence of irAEs in the cohort was 28%, with no significant difference between NHB and other racial groups (29% vs. 27.5%). However, females [OR 2.3 (1.1-4.8)] and patients who did not have Medicare or private insurance (i.e had Medicaid or MassHealth) were found to have a higher incidence of irAEs [OR 2.7 (1.2-5.7)]. With a median follow-up time of 363 days, the proportion of patients who were progression-free was greater in patients who had experienced irAEs than in those who did not experience irAEs [HR for time to progression 0.46 (0.23 – 0.92)]. The association between irAEs and improved PFS in NHB patients was similar to the overall population [median PFS 246 vs. 181; HR 0.87 (0.58-1.29)]. Higher ECOG status, higher Charlson Comorbidity Index and receiving ICIs as 2nd or subsequent line therapy were independently associated with worse PFS. Conclusions: Our single-institution study demonstrated a similar incidence of irAEs in patients with NSCLC across different racial and ethnic groups. As in prior studies, patients undergoing treatment with ICIs and experiencing irAEs had significantly better outcomes. We found that the association between the development of irAEs and improved treatment outcomes was independent of race and ethnicity, supporting the importance of making unbiased treatment recommendations without regard to these factors. [Table: see text]
piRNA-14633 underexpression as an independent prognostic marker in non-small cell lung cancer.
Authors: Peng Wei , Mei Jingfeng , Feng Jifeng 
Published: June 2023

e21223 Background: To determine the expression and function of piRNA-14633 in non-small cell lung cancer (NSCLC) samples were taken from cancer lesions (n = 30) and adjacent normal tissue (n = 30) in NSCLC patients. Methods: piRNA-14633 expression was determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The effect of piRNA-14633 overexpression was examined in vitro utilizing a human NSCLC cell line H1650 stably transfected with a recombinant lentivirus and compared to empty vector-transfected controls. piRNA-14633 overexpression was verified by RT-PCR. The expression of proteins involved in cell cycle regulation (CDK4) and apoptosis (Bcl-6) and cell migration (MMP-9) in cells was analyzed by Western blot. The effect of piRNA-14633 overexpression on cell viability and proliferation was assessed by an MTT assay cells. Flow cytometric analyses were used to evaluate the effect of piRNA-14633 expression on cell cycle distribution and apoptosis. The migration and invasion potential of piRNA-14633 cells was examined by plating cells in Matrigel-coated chambers. Results: The level of piRNA-14633 expression was found to be significantly lower in NSCLC tissue than normal tissues (P < 0.05). Decreased expression of piRNA-14633 was significantly correlated with lymph node metastasis, clinical stage, and histological grade of patients with NSCLC (P < 0.05). Meanwhile, loss of piRNA-14633 expression correlated significantly with poor overall survival time by Kaplan-Meier analysis (P < 0.05). The result of biological function shown that H1650 cell-transfected piRNA-14633 had a lower survival fraction, higher percentage of the G0/G1 phases, higher cell apoptosis, significant decrease in migration and invasion, and lower CDK4, Bcl-6, and MMP-9 expression compared with H1650 cell without piRNA-14633 (P < 0.05). Conclusions: Reduced piRNA-14633 expression is associated with increased disease severity, suggesting it is a negative regulator of NSCLC and can serve as a prognostic indicator.
Key factors associated with response in the treatment of liver metastatic melanoma by cryoablation combined with PD-1 blockade therapy: The Cryo-Fire-001 study.
Authors: Shen Lujun , Zhang Xiaoshi , Fan Weijun 
Published: June 2023

e21500 Background: Liver metastasis remains a challenge in the treatment of advanced stage melanoma through immunotherapy. Although our previous study showed cryoablation could enhance the efficacy of PD-1 blockade therapy in the treatment of melanoma patients with liver metastasis, the key factors correlated with survival and treatment response remains unknown. Methods: Between 2018 and 2022, 45 melanoma patients receiving combined PD-1 blockade therapy and cryoablation of liver metastasis were retrospectively analyzed. The technical parameters of cryoablation, the sequence of the combined treatment, tumor characteristics, important immune markers and their correlations with treatment response were evaluated. The associations between key factors and overall survival (OS) were determined by Cox regression. Results: Of the 45 patients, the 3-month overall response rate (RECIST 1.1 criteria) is 26.7%. Multivariate analysis showed the number of metastatic organs ( > 2 vs ≤2; HR 3.54; 95% CI 1.32-9.49; P = 0.012), pretreatment LDH level ( > 300 vs ≤300 U/L; HR 4.59; 95% CI 1.78-11.85; P = 0.002) and diameter of ablated lesion ( > 30 vs ≤30 mm; HR 3.27; 95% CI 1.17-9.15; P= 0.024) were independent unfavorable prognostic factors for OS. Further analysis showed patients with larger intrahepatic tumors ablated had larger tumor size (P < 0.001). A scatter plot by the two key variables showed patients with intrahepatic tumor size less than 45 mm and size of ablated lesion less than 30 mm had a marginally higher rate of 3-month response (10/28, 35.7%) compared to those not (2/17, 11.7%; P = 0.076). Large diameter of ablated lesion ( > 30 mm) require more ablation needles and cause greater elevation in the level of IL-6, CD8+T cell to Treg cell ratio and neutrophil to lymphocyte ratio after cryoablation while these changes disappeared when tested one month later. Conclusions: Fine selection based on baseline characteristics of patients and size of intrahepatic lesion for cryoablation are essential to achieve a high response rate during cryoablation-PD-1 combination treatment for liver metastatic melanoma.
Socioeconomic and demographic factors on academic center accessibility in sebaceous adenocarcinoma: An NCDB analysis.
Authors: Wu Xinxin , Swedek Michelle , Silberstein Peter T. , Vardell Victoria 
Published: June 2023

e21501 Background: Sebaceous adenocarcinoma (SA) is a rare, aggressive adnexal tumor shown to have both local and distant metastatic potential. The 5-year overall survival rate for this cancer is 78% for localized/regional disease and 50% for metastatic disease. Improved survival in other skin malignancies, such as melanoma, has been previously linked to treatment at academic cancer centers. The National Cancer Database (NCDB) was analyzed to determine variables impacting treatment at academic versus non-academic facility types in SA. Methods: A retrospective cohort analysis using the NCDB from 2004 to 2019 included patients diagnosed with histologically confirmed SA (N = 3,378). Socio-demographic factors (sex, age, race, Hispanic status, insurance type, urban/rural designation, facility location, education, income, distance from facility, and Charlson-Deyo score) were analyzed using Pearson Chi-squared tests and multivariate analysis of factors on academic center accessibility (facility type) was performed via binary logistic regression. A significance level of 0.05 was used. Results: The number of cases diagnosed with SA has steadily increased from 2004 to 2019 (152 and 287, respectively, R2 = 0.894). Most patients were male (59.1%), White (89.8%), not Hispanic (89.6%), insured (95.7%), and lived in an urban area (98.4%). There was a statistically significant difference between sex, race, insurance type, urban/rural designation, facility location, education, income, and distance from residence to the facility on academic facility type. Male patients were 1.3 times more likely to access academic centers compared to female patients (p < 0.001, CI = [0.681 - 0.911]). Patients with median household incomes in the top quartile were also 2.2 times more likely than those in the bottom quartile to receive treatment at an academic center (p < 0.001, CI = [1.676 - 2.992]). Conclusions: There has been an upward trend in the diagnosis of SA since 2004 with a predilection for White males. Female patients and patients with a lower income are less likely to receive treatment at an academic center. Given the rarity of the disease, this study serves as a valuable tool for understanding the factors associated with facility-type access. Future studies aim to determine the effect of academic center type on overall survival. Additional research is needed to understand the difference in treatment at academic versus non-academic facilities.