bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of National Comprehensive Cancer Network (NCCN) guideline adherence for lung cancer in a community teaching hospital during COVID-19 pandemic.
Authors: Paravathaneni Mahati , Thota Vihitha , Baralo Bohdan , Mulla Sana , Choi Eugene Jinkyu , Thirumaran Rajesh 
Published: June 2021

e20589 Background: Coronavirus disease 2019 (COVID-19) evolved into a worldwide pandemic leading to devastating complications. In healthcare, significant changes were made to reallocate resources to cater to an increasing number of hospital admissions and prevent infection spread. Reallocation of the health care staff led to the scarcity of care in outpatient facilities, including infusion centers, until the widespread adoption of Telehealth. Treating lung cancer patients with immunochemotherapy and radiotherapy has been incredibly challenging due to the pandemic, especially in regard to balancing malignancy treatment with limiting exposure of vulnerable patients to acute life-threatening infection. In addition, being unable to provide appropriate treatment to cancer patients can result in decreased functional capacity, loss of treatment window, and increased mortality. A multidisciplinary approach can prevent these outcomes by anticipating challenges early and streamlining resources appropriately to provide better patient care. In this study, we aimed to assess the adherence of NCCN guidelines for lung cancer at a community hospital in Philadelphia during the pandemic. Methods: A retrospective chart review was performed of patients diagnosed and receiving active treatment for primary lung cancer between March 1, 2020, and December 31, 2020, at Mercy Catholic Medical Center. Fifty cases of primary lung cancer undergoing active treatment were identified. Type and staging of lung cancer, NCCN guidelines’ adherence, COVID-19 exposure, and missed treatments were reviewed and analyzed. Results: Of the 50 cases reviewed, 92% had non-small cell lung cancer (NSCLC), and 8% had small cell lung cancer (SCLC). Among NSCLC, 72% had adenocarcinoma, 12% had squamous cell carcinoma, and 8% had large cell carcinoma. Stage IV lung cancer consisted of 46%, followed by 34% of stage I, 14% of stage III, and 6% of stage II. NCCN guideline-directed treatment was initiated in 88% (44/50) of the total patients, with the remaining 12% of the patients either refusing treatment (8%) or were lost to follow-up (4%). COVID-19 infection was diagnosed in 35% of the patients, of which 60% missed less than two chemotherapy sessions and 40% of COVID-19 positive patients who required hospitalization missed more than two cycles. 28% of patients missed treatment sessions due to other factors. This resulted in 61% (27/44) of patients having a disruption in NCCN guideline-directed treatment at some point during the pandemic. Conclusions: Our study results reflect upon the need for developing effective strategies in managing cancer patients. When possible, switching to oral regimens, redefining regimen administration intervals, postponing invasive investigations for asymptomatic patients, and utilizing telemedicine as appropriate should be considered.
Identification of RET fusion as mechanisms of resistance to EGFR tyrosine-kinase inhibitors.
Authors: Bing Zhongxing , Wang Weiran , Wang Danhua , Ma Tonghui 
Published: June 2021

e21074 Background: Responses to EGFR-targeted therapy are generally temporary, due to inevitable drug resistance. Although RET fusions have been identified in resistant EGFR-mutant non–small cell lung cancer (NSCLC), their characteristics acquired resistance to EGFR tyrosine-kinase inhibitors (TKIs) are rarely investigated. Methods: We retrospectively reviewed next-generation sequencing data of EGFR+ lung cancer patients, and 8 patients were identified coexisting of EGFR mutations and RET fusion. Their treatment history was collected. Results: The co-occurrence of RET fusion with EGFR oncogenic variations was observed in eight patients, and all of the 8 patients have received previous EGFR-TKI treatment. EGFR mutations were including 4 L858R mutations, 4 exon 19 deletions, and 6 T790M mutations. And the partner genes of RET identified by NGS were including TRIM33 (2/8), GPRC6A (1/8), TLN1 (1/8), KIAA1598 (1/8), SPECC1 (1/8), TRIM24 (1/8) and CCDC6 (1/8). The allelic fractions (AFs) of first-generation EGFR-TKI sensitizing mutations were higher than AFs of EGFR T790M mutations as well as AFs of RET fusion. These RET fusions are fused with rare partner genes, rather than the most common KIF5B in lung cancer. Conclusions: This study extended the knowledge of RET fusion as resistance mechanism to EGFR TKIs in lung cancer. The detection of RET fusions may uncover potential resistance mechanisms of EGFR TKIs, which might inform therapeutic strategies, such as combination-therapy approaches.[Table: see text]
Comprehensive T-cell receptor repertoire of Chinese lung cancer patients related with age.
Authors: Yang Huaxia , Li Xiaoguang , Liu Xinyu , Wang Yadong , Xue Jianchao , Jia Ziqi , Yang Xiaoying , Xu Huihui , Bing Zhongxing , Guo Chao , Tian Zhenyu , Gao Chao , Gu Dejian , Chen Rongrong , Xia Xuefeng , Li Shanqing , Liang Naixin 
Published: June 2021

e21076 Background: Cancer is most commonly diagnosed disease worldwide and also a leading cause of death. Cancer is more common in older people, but it can also be found in younger people. As the importance of T cell receptor (TCR) repertoire gains appreciation, particularly given their potential utility for cancer immunotherapeutic prognostication, the characteristics of TCR repertoire are needed. We detected the complementarity determining region 3 (CDR3) by TCR sequence to describe the correlation between diversity and clonality in human’s immune system and age. Methods: The TCRβ repertoire of 47 stage Ia lung cancer patients were analyzed. Genomic DNA was extracted from peripheral blood or tissue, and used to amplified and sequenced the CDR3 region of rearranged TCRβ genes. Finally, we got the relative frequencies of patients T cell clones. Shannon index was calculated on the clonal abundance of all productive TCR sequences. Simpson index also was calculated to measure the clonality of TCR repertoire. MOI was a measure of the similarity in the T cell repertoire between tissue and blood taking into account the specific rearrangements and their respective frequencies. Results: In tissue, the Simpson index ranged from 0.00075 to 0.11466 (mean = 0.01343); Shannon index ranged from 2.91 to 8.95 (mean = 6.26). The age ranged from 27 to 78 (median = 63). Patients were divided into two groups based on median age. The older showed higher Shannon index (p = 0.005) but lower Simpson index (p = 0.0072) than younger patients in tissue. Further, the higher Shannon index was found in younger group in blood(p = 0.0411). Interestingly, the MOI of the older group was significantly higher than that of the younger group (p = 0.0181), suggesting that the older group had a relatively better TME immune response. Then, the usage of V and J gene segments were analyzed. Through statistical analysis and the frequencies of V and J gene usage, we identified that more V and J gene usage were different in older and younger patients. The TRBJ1-1 and TRBJ1-2 were more common in younger patients and TRBJ2-1 and TRBJ2-2 were more common in older patients. There was also more V gene usage different in both groups. Conclusions: Given that the use of certain TRBV regions is predominant in tumor tissues, our results suggested that there may be differences in immune responses of TME to tumors in younger and older patients.
Comparing active immunotherapy efficacy of PD-L1 ≥ 50% NSCLC patients: A systematic review and meta-analysis.
Authors: Hu Yi , Zhao Xiaochen , Bai Yuezong , Cui Longgang , Zhang Fan 
Published: June 2021

e21139 Background: Several therapies based on immune checkpoint inhibitors (ICIs) have been approved as the 1L standard of care for PD-L1≥ 50% advanced non-small cell lung cancer (NSCLC). However, little is known about the difference in efficacy between different strategies. We conducted a systematic review and meta-analysis to help clinicians choose more reasonable treatment options. Methods: We searched PubMed, Cochrane library, Embase and major conference proceedings from January 2010 to December 2020 for randomized controlled trials that had available subgroup hazard ratios (HRs) for overall survival according to PD-L1≥ 50%. Only drugs met primary outcome or approved by FDA were included for analysis. The primary outcome was the difference in overall survival (OS). HRs and 95% CI were calculated for the pooled OS using a random-effects model. p<0.05 was considered as statistical difference. Results: A total of 10 randomized controlled trials were included for this meta-analysis. The pooled HR and 95% CI for monotherapy, ICI plus chemotherapy and ICI plus ICI were 0.64 (0.55, 0.74), 0.64 (0.51, 0.79) and 0.70 (0.55, 0.90), respectively. There was no statistical differences between ICI monotherapy and ICI plus chemotherapy (HR 1.00, 95% CI 0.77- 1.30), between ICI monotherapy and ICI plus ICI (HR 0.91, 95% CI 0.69- 1.22) or between ICI plus chemotherapy and ICI plus ICI (HR 0.91, 95% CI 0.66- 1.27). Conclusions: For PD-L1≥ 50% NSCLC patients, active ICI monotherapies showed no different efficacy when compared with ICI combination therapies.
Primary and secondary resistance mechanisms in first, second and third generation tyrosine kinase inhibitors in EGFR mutant non-small cell lung cancer patients.
Authors: Suryavanshi Moushumi , Mattoo Sakshi , Sharma Sanjeev Kumar , Mehta Anurag , Batra Ullas 
Published: June 2021

e21142 Background: Different molecular mechanisms of on target and off target primary and secondary resistance have been observed in EGFR mutant NSCLC patients after first(1st), second(2nd) and third (3rd) generation of tyrosine kinase inhibitors(TKIs). Next generation sequencing(NGS) offers a comprehensive method of detecting these mechanisms to decide next line of treatment. Methods: We retrospectively analyzed 430 samples of NSCLC for primary and secondary resistance to 1st, 2nd and 3rd TKIs. NGS was performed using thermofischer Ion Torrent Oncomine Focus 52 gene Assay. These cases were divided into 4 groups.1)Primary resistance to first and second generation TKIs 2)Primary resistance to 3rd generation TKI 3)Secondary resistance to 1st and 2nd generation TKI 4) Secondary resistance to 3rd generation TKI.Last group was further subgrouped into A when 3rd generation TKI was offered as second line after 1st or 2nd generation TKIs on detection of T790M and subgroup B when it was given as first line. Results: Group1 had 13 cases. There were 2 cases of complex EGFR exon 19 mutation p.Glu746_Leu747delinsValPro, 4 cases of EGFR exon 20 insertion, 1 case of dual EGFR L833V & H835L mutation, 2 cases with EGFR amplification with EGFR exon 19 del and PIK3CA C420_P421del along with EGFR exon 19 del. Four cases had no additional abnormality. Group 2 had 5 cases:1 case had L858R and E709A dual mutation, 2 cases had KRAS G13C and KRAS G12V along with EGFR exon 19 del. One case had EGFR amplification and one case had MET amplification along with EGFR exon 19 del respectively.Group 3 had 34 cases including 10 cases of EGFR L858R and 24 cases of exon 19 deletion.T790M mutation was detected in 8 patients, MET amplification in 7 cases,one case had both T790M and MET amplification. One case lost the primary EGFR exon 19 del. Others mutations detected were KRAS G13C, PIK3CA H1047R, TP53 R213Q and TP53 C242fs. Group3 had 15 cases with 7 cases in subgroup A and 9 cases in subgroup B. In subgroup A T790M mutation was lost in 6 out of 7 cases.One case which lost T790M developed ALK translocation.One case of EGFR exon 19 del retained EGFR T790M with EGFR C797S in cis allele. Other mutations detected were PIK3CA E542K and KRAS G12C. In subgroup B one case showed EGFR C797S(both cis and trans) besides the primary EGFR exon 19 del. One case showed BRAF G469A along with EGFR exon 19 del. Other mutations detected were CTNNB1 D32N, KRAS G12V, and PIK3CA E542K. Conclusions: Primary and secondary acquired resistance is unavoidable in EGFR mutant advanced NSCLC on any generation of TKIs. NGS offers an advantage in diagnosing mechanism of resistance for further choice of therapy.
Interprofessional care team practices and perspectives on immuno-oncology (IO) therapies for metastatic non-small cell lung cancer (mNSCLC): Insights from a nationwide survey.
Authors: Farris Breanne Y. , Jacobson Anne , Carter Jeffrey D. , Heggen Cherilyn , Socinski Mark A. 
Published: June 2021

e21147 Background: Appropriate molecular testing, biomarker-directed treatment selection, and management of immune-related adverse events (irAEs) are essential best practices for managing patients with mNSCLC who are eligible for IO therapies. Identifying real-world challenges among mNSCLC care teams is necessary to inform educational interventions that support optimal care. Methods: From 10/2020 to 01/2021, 75 health care professionals (HCPs) who treat mNSCLC completed surveys assessing practice patterns, challenges, and confidence related to the use of IO therapies. To reflect current real-world practice across treatment settings, surveys were administered at 10 clinics nationwide and through a large oncology practice network. Results: Participants represented the interprofessional mNSCLC care team: oncologists (50%), primary care physicians (23%), advanced practice professionals (13%), and nurses (13%). Nearly one-third reported that PD-L1+ mNSCLC presented greater management challenges than other mNSCLC sub-types. Regarding patients who are eligible for IO therapies, the most commonly reported challenges were applying pathology results to treatment decisions (29%), differentiating IO therapies (19%), and managing irAEs (19%). Case-based questions revealed gaps in care relative to guidelines: 65% incorrectly identified which patients should be tested for PD-L1; 49% failed to identify the most appropriate IO regimen based on case details; and 65% failed to identify an inappropriate strategy for managing mild irAEs (Table). Further, HCPs reported inappropriate reasons to exclude patients from IO therapy and suboptimal use of supportive care measures. Confidence gaps echoed these challenges; most HCPs reported less-than-high confidence in their ability to apply molecular test results to treatment decisions (80%), differentiate IO therapies based on PD-L1 expression (65%), or coordinate irAE care (85%). Conclusions: In current real-world practice, mNSCLC care teams report challenges in biomarker testing and interpretation; differentiation of IO therapies based on patient, disease, and treatment factors; and irAE management. These identified gaps represent key opportunities for future interventions to improve mNSCLC care. [Table: see text]
Back to the well: Can patients with advanced non-small cell lung cancer benefit from changing PD-1/PD-L1 inhibitors after progression?
Authors: Newman James , Lee Chung-Shien , McGovern Kerri , Seetharamu Nagashree 
Published: June 2021

e21194 Background: Immune checkpoint inhibitors (ICIs) have transformed the standard of care of non-small cell lung cancer (NSCLC) and are capable of inducing a sustained response in a cohort of patients. For those who progress while on ICIs and do not have a targetable mutation, options are typically reduced to chemotherapeutic regimens which have a higher probability of toxicity. In patients with a suboptimal performance status or those who are opposed to receiving chemotherapy and are not eligible or interested in clinical trials, treatments are unfortunately limited. Patients who progress on one ICI do not receive a different ICI as part of standard care in subsequent lines of therapy. Data behind switching ICIs, particularly to those with a different mechanism of action (ie anti-PD-1 followed by anti-PD-L1 or vice versa), are lacking. We evaluated the efficacy of receiving a 2nd ICI in patients with NSCLC. Methods: A single-center, IRB-approved retrospective analysis was conducted of NSCLC patients treated with two different ICIs from March 2015 to July 2020. ICIs were given either in combination with chemotherapy or as monotherapy. Patient and tumoral characteristics, including PD-L1 status (if available) and sequence of ICIs, were captured. A positive PD-L1 was defined as PD-L1 expression > 0%. Progression-free survival (PFS) of each ICI (defined as PFS1 and PFS2) were calculated in months (m) for each patient. Median PFS2 was compared between groups stratified by a cutoff median PFS1 of 3m, sequence of PD-1 and PD-L1 inhibitors, and PD-L1 positive and negative subsets. Mood’s median test was used to compare medians. Results: 26 patients were included in the final analysis. 19/26 patients had a PFS1 > 3m. For this cohort, the median PFS2 was 2.5m (Range: 0.1-36.2) compared to median PFS2 of 1.6m (Range: 0.6-15.9) in patients with PFS1 < 3m (p=0.1847). 15 patients received a PD-1 inhibitor followed by a PD-L1 inhibitor. In this subgroup, the median PFS2 was 1.2m (Range: 0.2-36.2). Alternatively, 7 patients received a PD-L1 inhibitor followed by a PD-1 inhibitor and the median PFS2 in this cohort was 2.3m (Range: 0.1-15.9) (p=0.6471). PD-L1 data was available for 19 patients. 8/19 patients with positive PD-L1 had a median PFS2 of 3.6m (Range: 0.2-13.3) compared to median PFS2 of 1.3m (Range: 0.1-36.2) in patients with negative PD-L1 (p=0.2599). Conclusions: Treatment with a 2nd ICI can potentially provide a modest benefit in patients with advanced NSCLC, and some may even experience a very prolonged response. PFS1, sequence of PD-1/PD-L1 inhibitors, and PD-L1 expression did not show any significant correlation with PFS2. Using a 2nd ICI should be considered for advanced NSCLC patients with diminished performance status or limited treatment options.
Spectrum of BRAF mutations in Indian patients with NSCLC: A molecular kaleidoscope.
Authors: Sharma Mansi , Nathany Shrinidhi , Soni Satyajeet , Jain Arpit , Mehta Anurag , Jain Parveen , Batra Ullas 
Published: June 2021

e21199 Background: Mutations in the BRAF gene (0.8%-8% cases of NSCLC) comprise a molecularly heterogeneous group, with the canonical V600E mutation as well as myriad variants. Traditionally, diagnostics utilize modalities like mutation specific IHC or allele specific real-time PCR for detection of V600E variant and may underestimate the true prevalence of non-V600E variants. Broader panel next generation sequencing (NGS) testing may be a better modality for detecting them and this may have potential therapeutic implications. This retrospective study of patients with BRAF mutated NSCLC looked at their molecular and clinicopathologic spectrum. Methods: 260 patients underwent panel based NGS testing between 2017-2020. BRAF mutant cases, detected at any point during the course of their disease, were reviewed for clinical, pathologic, molecular features; as well as associated treatment and outcomes. Results: BRAF alterations were seen in 14/260 (5.38%) patients. Median age of the cohort was 62 years (range: 39-86 years) with a female predilection (8/14, 57.1%). BRAF V600E mutation was seen in 6 (42.9%) patients and 8 (57.1%) harbored a non-V600E alteration; the spectrum of which included G466E, G469A, N581I, V600_K601delins, D594G, L597Q, G649V and a TRIM24-BRAF fusion. All patients were never smokers with an adenocarcinoma histology.11 (78.6%) patients had extra thoracic metastases, and 2 (14.3%) cases had metastases to the brain at diagnosis. 11/14 (78.6%) patients had presence of liver metastases (V600E vs non V600E: 43% vs 57%, p = 0.09). 11 patients took treatment at our centre and two patients received anti-BRAF therapy. One patient with V600E mutation received vemurafenib. The other patient with a nonV600E mutation (V600_601delins, detected on NGS) received combination dabrafenib-trametinib with an ongoing partial response at 6 months. 8 patients received chemotherapy and median PFS was 4.8 months, similar for all mutation types. Median OS for the entire cohort was not reached owing to high censorship. Conclusions: This single centre study depicts distinct clinicopathologic features in Indian patients with BRAF mutant NSCLC. The higher prevalence of non-V600E mutation may be attributed to increased use of broader panel based NGS testing as opposed to sequential single gene testing. One of the patients with a non-V600E mutation responded to targeted therapy, hence clinicians should be aware of this spectrum of potentially targetable BRAF mutations.
Overweight or obese patients may take longer to respond and be less responsive to immune checkpoint inhibitors in non-small cell lung cancer: A retrospective review.
Authors: Palmer John P. , Cao Yenong , Ibrahim Samer , Dhawan Natasha , Afzal Muhammad Zubair , Shirai Keisuke 
Published: June 2021

e21209 Background: Immune checkpoint inhibitors (ICI) are now the standard of care in the treatment of non-small cell lung cancer (NSCLC). ICIs may be used as monotherapy or in combination with chemotherapy. Increased recruitment of inflammatory cells in the tumor micro-environment is associated with a poor response to ICIs. Although obesity is a risk factor for many types of cancers, including lung cancer, it is associated with a low systemic inflammation state. This creates an effect known as the “obesity paradox,” resulting in better treatment-related outcomes in overweight and obese patients receiving ICIs. However, in obese patients, the neutralizing interleukin (IL) - 1β level is high, which can decrease the responsiveness to ICI. We aim to study the effect of increased weight on treatment-related outcomes in NSCLC patients receiving ICI. Methods: We conducted a retrospective analysis on 178 NSCLC patients treated with ICIs, such as pembrolizumab, nivolumab, ipilimumab/nivolumab or atezolizumab, alone or in combination with chemotherapy. Overweight was defined as having a BMI of 25 – 29.9 while obesity was defined as having a BMI of ≥ 30. Overall survival (OS), progression free survival (PFS), best radiographic response, and the time to achieve radiographic response were evaluated. Cox regression univariate and multivariate analyses were performed. Logistic regression and Chi-square tests were applied. Results: Of the 178 patients with NSCLC, 81% had adenocarcinoma, and 19% had squamous, adenosquamous, or large cell carcinoma. The majority of patients were female (56.2% vs. 43.8%). Overall, 48.6% patients were overweight or obese. The objective response rate (ORR) was 45.1% and the disease control rate (DCR) was 75.8%. The ORR was 37% in overweight/obese patients compared to 52% in patients with a normal weight (p = 0.06). The DCR was 76% vs. 73.9%, (p = 0.7). The median time to achieve the best radiographic response was 3.7 months in overweight/obese patients compared to 2.5 months in those of normal weight (p = 0.2). A considerably higher proportion of the patients progressed in overweight/obese category (80.7% vs. 69.3%, P = 0.08). However, there was no significant difference in median PFS between the two categories (7.4 vs. 8.1 months, P = 0.2). The overall survival was not significant different between both categories (15.9 vs. 16.8 months, P = 0.5). Conclusions: Our study suggests that obesity and overweight status can result in a low response rate to ICIs in NSCLC patients and can delay the time to achieve the best radiographic response per RECIST criteria. However, we did not observe any significant impact on the overall or progression-free survival. A large, population-based study will help to elucidate the impact of weight on the responsiveness to ICI.