tbuckley/cabot-search huggingface dataset:
Sugemalimab in locally advanced and advanced Chinese NSCLC: A real-world retrospective study.
Authors: Jiayu Liu, Yan Wang, Qi Wang, Ke Yang, Tongji Xie, Dantong Sun, Lige Wu, Li Junling, Puyuan Xing
Journal: Journal of Clinical Oncology (2024)

e20575 Background: Lung cancer is a major cause of cancer deaths in China. Immunotherapy has emerged as a promising treatment approach for advanced NSCLC without sensitive mutations. Sugemalimab, a fully human immunoglobulin G4 monoclonal antibody, retains its Fc function, inducing antibody-dependent cellular phagocytosis. This study aims to evaluate the real-world effectiveness and safety of Sugemalimab in various treatment patterns, particularly with radiotherapy, in Chinese NSCLC patients with locally advanced or metastatic disease. Methods: We retrospectively evaluated locally advanced (LA-) and metastatic (m-) NSCLC patients (pts) treated with Sugemalimab in Cancer Hospital, Chinese Academy of Medical Sciences from Feb. 2022 to Sep. 2023. Demographic characteristics, clinical features, genetic landscape and therapy patterns were collected. We employed descriptive statistics to determine the Objective Response Rate (ORR) and Disease Control Rate (DCR), and used the Kaplan-Meier method for estimating Progression-Free Survival (PFS) and Overall Survival (OS). Safety profiles, including adverse events and immune-related pneumonitis, were similarly analyzed. Results: 76 pts with LA-NSCLC and mNSCLC were enrolled. Majority were male (92.1%) and smokers (84.2%) and ECOG PS 0-1 (78.9%). Median age was 66. Squamous-cell carcinoma was found in 44 pts (57.9%). The main metastatic sites were bone, brain, liver, lung and lymph node for mNSCLC pts. Genetic profiling in 39 pts revealed TP53 mutations in 19 (48.7%) and KRAS mutations in 10 (25.6%). A total of 38 pts (51.3%) received 1L Sugemalimab therapy, while 21 pts (27.6%) receiving 2L. Main treatment pattern was Sugemalimab plus platinum-based chemo. Radiotherapy (RT) was main local therapy approach, concurrent with Sugemalimab in 18 pts. Majority of pts received either volumetric modulated arc therapy or intensity-modulated radiation therapy to thoracic lesions. Tomotherapy was administered to brain metastases in 2 pts. The median follow-up time was 9.18m at this cut-off date. 16 pts receiving Sugemalimab plus chemo achieved objective response (ORR 44.4%) and DCR was 91.5% in 1L therapy. Median PFS (mPFS) has not been reached. PFS rate at 6m, 12m was 75.6%, 62.1% respectively. 1L OS was immature. For pts receiving additional thoracic RT concurrent with 1L systematic therapy, mPFS was still not mature. PFS rate was 82.4% at 6m and 74.9% at 12 m. Common RT-related side effects were radiation pneumonitis, radiation esophagitis and skin injury. None immune-related pneumonitis was found in this population. Only one case of immune-related pneumonitis was observed in a pts without RT. Conclusions: Our study demonstrated Sugemalimab-based therapy provide clinical benefits to LA-NSCLC and mNSCLC with good safety in real-world setting. The combination treatment of Sugemalimab with radiotherapy illustrates low pulmonary toxicity and superior tolerability.
Real-world data analysis of first-line targeted therapy for patients with non-small cell lung cancer with different EGFR mutation status in a tertiary care hospital.
Authors: Yang Peng, Ziyi Liao
Journal: Journal of Clinical Oncology (2024)

e20586 Background: Lung cancer is still the malignant tumor with the highest incidence and mortality rate in the world, of which non-small cell lung cancer (NSCLC) accounts for about 85%. The EGFR mutation rate in Asians is 30%-60%, with exon 19 deletion mutations and exon 21 L858R point mutations accounting for about 90% of EGFR mutations, which are the classic EGFR mutation types. The two have significant differences in clinical characteristics, and some clinical trials have shown differences in efficacy between different subgroups, but whether they exist in the real world needs to be further confirmed. Meanwhile, the efficacy of first-line targeted therapy in patients with coexisting mutant NSCLC harboring different EGFR classical mutations and whether there is a difference in different subgroups has not been conclusively determined. Methods: To collect general clinical data and their genetic test reports of NSCLC patients diagnosed with gene mutations who attended the Affiliated Hospital of North Sichuan Medical College from January 2019 to December 2021 for follow-up, with a follow-up date of June 30,2023, as the end date. Kaplan-Meier survival analysis and log-rank test were applied to compare:1)the median PFS in different subgroups of patients with no co-mutation classic EGFR mutation;2)the median PFS in patients with co-mutation classic EGRR mutation and no co-mutation classic EGFR mutation;3)the median PFS in different subgroups of patients with no co-mutation 19-Del/L858R and with co-mutation 19-Del/L858Rpatients;4)median PFS of patients between co-mutated 19-Del and L858R subgroups. Results: The median PFS of 19Del was significantly better than that of L858R in different subgroups of EGFR classical mutations (14.0 months vs. 8.1 months, p = 0.004 &lt; 0.05). The median PFS of EGFR classical mutation was significantly better than that of EGFR classical mutation with co-mutation,11.1months vs. 5.8 months, respectively, p &lt; 0.001. In different subgroups,19Del median PFS was superior to 19Del co-mutation (14.0 months vs. 6.1 months, p = 0.001 &lt; 0.05),and L858R median PFS was superior to L858R co-mutation (8.1 months vs. 5.8 months, p = 0.449 &gt; 0.05). 19Del co-mutation and L858R co-mutation median PFS were not observed in the analysis of the same simple 19del first-line targeted therapy survival benefit was significantly better than the similar survival benefit of L858R, whose median PFS was 6.1 months vs. 5.8 months, respectively, p = 0.449&gt;0.05, the difference was not statistically significant. Conclusions: The survival benefit of first-line targeted therapy for 19Del in the real world is superior to that of L858R, while the clinical benefit of first-line targeted therapy is poor for classical mutations in EGFR with co-mutations, and combinations with other therapeutic modalities should be considered.
Double lung transplantation in patients with recent history of malignancy.
Authors: Tarik Demir, Ankit Bharat, Liam IL-Young Chung, Wongi Woo, Carolyn Moloney, Chan Mi Jung, Rade Tomic, Young Kwang Chae
Journal: Journal of Clinical Oncology (2024)

e20614 Background: Recent history of malignancy has been considered as a contraindication for double lung transplantation (DLT) due to concerns for risk of cancer recurrence and worse outcomes. However, the relationship between the recent malignancy history and lung transplantation mortality remains unclear. Methods: Among patients treated with DLT between 09/2021 and 02/2024 in single institution, patients with a recent history of other cancers were included in this study. All patients had enrolled in cohort C of the DLT registry aimed for lung-limited malignancies (DREAM) study (NCT05671887). Exclusion criteria include extrapulmonary metastatic disease and medical ineligibility for DLT. All patients were followed up with computed tomography every 12 weeks. Results: Four patients were included; three (75%) patients with a histology of NSCLC (squamous cell, stage Ib-IIIb), and one (25%) with prostate adenocarcinoma (stage IIc). The median no-evidence-of-disease (NED) time was 19.5 months (0-41). Patients were aged 57-68, three (75%) were male. The indication for DLT was chronic obstructive pulmonary disease (1/4, 25%), interstitial lung disease (2/4, 50%), and idiopathic pulmonary fibrosis (1/4, 25%). All patients had high oxygen requirements before DLT. The median duration of the waitlist for DLT was sixteen days (3-61). There was no in-hospital mortality and the median hospital stay was 20.5 days (16-32). During a median follow-up of 2.5 months (range 0-9), rejection and post-transplant malignancy did not occur in any of the cases (Table 1). Conclusions: Four patients with history of cancers underwent DLT without significant complications. The median post-transplant follow-up was 2.5 months (0-9). Ongoing DREAM study cohort C will continue to investigate the role of DLT in patients with a recent history of malignancy. Clinical trial information: NCT05671887 . [Table: see text]
Comparison of clinical outcomes of stable disease with confirmed tumor reduction and RECIST partial response for tebentafusp in metastatic uveal melanoma (mUM).
Authors: Alexandra Ikeguchi, Takami Sato, Marcus O. Butler, Richard D. Carvajal, Joseph J Sacco, Alexander Noor Shoushtari, Jessica Cecile Hassel, Paul D. Nathan, Josep M. Piulats, Douglas Buckner Johnson, Jason J. Luke, Enrique Espinosa, Serge Leyvraz, Laura Collins, Ramakrishna Edukulla, Piruntha Thiyagarajah, Omid Hamid
Journal: Journal of Clinical Oncology (2024)

9529 Background: Tebentafusp (gp100 x CD3) has demonstrated an overall survival (OS) benefit in mUM. Benefit was observed in patients (pts) who achieved a RECIST v1.1 partial response (PR), stable disease (SD) and even progressive disease (PD) (Nathan 2021). In Phase (Ph) 1, some melanoma pts had SD with tumor reduction &gt; 10% that was confirmed at ≥ 1 subsequent scan (referred to as minor response, MR). In Ph 2, an analysis of MR was pre-specified as an endpoint and presented here. Methods: 127 HLA-A*02:01+ pts with previously treated mUM received weekly intravenous tebentafusp following intra-pt dose escalation of 20mcg Week 1, 30mcg Week 2 and 68mcg Week 3+ (NCT02570308; Carvajal 2022). Radiologic assessments were performed every 8 weeks until week 40, then q12 weeks. Tumor assessment was evaluated by a blinded independent review committee per RECISTv1.1. MR was prospectively defined as RECISTv1.1 best response of SD with reduction in sum of target lesions of -10% to -29% and which was confirmed ≥ 4 weeks later. ctDNA levels were assessed using a targeted mPCR-NGS assay for mutations in 15 genes including mUM oncogenes GNAQ, GNA11, SF3B1, CYSLTR2, PLCB4 and EIF1AX (Natera). Molecular response was defined as ≥ 0.5 log [68%] ctDNA reduction by week 9. Data cut off: Oct 2022. Median duration of follow-up was 46 months. Results: Of 127 pts, the clinical benefit rate of PR + SD was 50% (64/127). 25% (32/127) had any tumor reduction that was confirmed on ≥ 1 subsequent scan, including 6 PR (ORR 5%) and 26 SD (20%). 8/26 SD (6% of 127) met the pre-defined threshold for MR, most (5/8) had &gt;20% reduction. The median duration of response for PR and MR were 8.7 months and 10.6 months, respectively. The estimated percent of pts with PR and MR remaining in response at Month 20 were 20% and 33%, respectively. 3/6 PR pts were alive ≥ 3 years vs 3/8. 58% of PR + SD pts with evaluable ctDNA had a molecular response (26/45), including 2/4 PRs and 5/5 MRs. Conclusions: This Ph2 UM study prospectively confirmed that a subset of SD patients had tumor reduction over multiple scans. The frequency of minor response was similar to that of PR and had similar durability, OS and ctDNA molecular response. SD with confirmed tumor reduction is an emerging endpoint for the ImmTAC platform and will be studied in other trials (NCT05549297, NCT04262466). Clinical trial information: NCT02570308 .
The 15-gene expression profile test is independent from PRAME and 7-gene next-generation sequencing: Results from 3,267 clinically tested uveal melanomas.
Authors: Robert W. Cook, Katherina Alsina, Jennifer J. Siegel, Kristen M. Oelschlager, Sherri Borman
Journal: Journal of Clinical Oncology (2024)

9598 Background: The 15-gene expression profile (15-GEP) test is the gold standard in the US for metastatic risk prediction in uveal melanoma (UM). Studies have shown that the 15-GEP is superior to and independent of other clinicopathologic and molecular risk factors, including PRAME expression status and BAP1 mutation status. Supplemental tests for PRAME and the 7-gene NGS panel ( BAP1, SF3B1, EIF1AX, GNA11, GNAQ, CYSLTR2, PLCB4)are validated and can now be run clinically from the same biopsy specimen. However, the discordance between 15-GEP, PRAME and NGS in clinical specimens is unknown. This study aimed to determine whether PRAME status or DNA mutation status could be used to predict the 15-GEP result. Methods: Data from fine-needle aspiration biopsy or formalin-fixed paraffin-embedded UM specimens submitted for routine comprehensive clinical testing with all three commercial tests (15-GEP, PRAME, and NGS) between February 2018 and December 2023 were collected through an Institutional Review Board-approved protocol. Results: Overall, 3267 tumors with comprehensive molecular testing were analyzed. 15-GEP testing yielded 65.9% (n=2152/3267) Class 1 and 34.1% (n=1115) Class 2 tumors. While Class 2 tumors were more than twice as likely to be PRAME(+) vs Class 1, 54.3% (606/1115) of Class 2 cases were PRAME(–), and 20.9% (450/2152) of Class 1 cases were PRAME(+) resulting in a PRAME/15-GEP discordance rate of 32.3% (10-56/3267). Mutations in genes associated with increasing metastatic risk ( EIF1AX, SF3B1, and BAP1, respectively) were identified in 58.7% (1918/3267) of cases. Most EIF1AX mutations (569/623, 91.3%) occurred in Class 1 tumors that were PRAME(–), while most SF3B1mutations were found in Class 1, PRAME(+) tumors (244/404, 60.4%). Most BAP1 mutations (863/976, 88.4%) occurred in Class 2 (high risk) tumors, of which 53.9% (465/863) were PRAME(–). Importantly, 56.0% (1205/2152) of Class 1 tumors did not harbor detectable EIF1AX or SF3B1 mutations, and 22.6% (252/1115) of Class 2 tumors did not harbor a detectable BAP1 mutation, yielding an NGS/15-GEP discordance rate of 44.6% (1457/3267). Conclusions: The validated PRAME and NGS tests described here, which can be performed from the same initial biopsy sample taken for 15-GEP testing, provide results that are not systematically associated with 15-GEP class. Given that the 15-GEP has been shown to be superior to both PRAME and NGS in predicting metastatic outcomes, it is recommended that these supplemental tests only be considered in the context of a 15-GEP test result to prevent potentially over or under identifying high-risk biology. An ongoing prospective study with long term outcomes for over 1700 UM patients led by the Collaborative Ocular Oncology Group (COOG2) will provide insight into how best to effectively integrate these supplementary biomarkers with the 15-GEP class result.
The effect of an online micro CE/CME on the multidisciplinary care of patients with nonmelanoma skin cancer.
Authors: Michelle Arielle Worst, Andrew Small, Deborah Middleton, Yoji Yamaguchi, Meng Yuan, Sukhbir Bahra, Vishal A. Patel
Journal: Journal of Clinical Oncology (2024)

e21006 Background: Nonmelanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC), are the most common malignancies diagnosed in the US and worldwide. While most are successfully cured with local therapies or surgery alone, immunotherapy agents have been added to the arsenal for advanced tumors that are unresectable or unlikely to be cured with surgery alone. Thus, the multidisciplinary care model in this clinical setting has numerous advantages; however, many healthcare professionals (HCPs) may not fully recognize the role of their colleagues and their value in caring for affected patients. The objective of this study was to assess the educational impact of an online micro continuing [medical] education (CE/CME) activity on the knowledge and competence of HCPs’ with respect to the role and value of the multidisciplinary team in the optimal care of patients receiving immunotherapy for NMSC. Methods: The educational activity consisted of a collection of six online video-based micro-CE/CME-certified chapters, presented by six respected NMSC experts, allowing learners to choose their chapters for participation. Educational impact was assessed with repeated paired pre-/post-assessment study design, where individual participants served as their own control. A McNemar’s test assessed significant levels of changes reported with P values &lt;.05 considered statistically significant. The activity launched September 2023; data were collected until January 2024. Results: The educational activity resulted in overall statistically significant improvements in HCPs’ knowledge and competence after education by chapter and by HCP audience type ( P &lt; .01), including oncologists, dermatologists, surgeons, nurses, and pharmacists. Results presented below highlight the improvements in HCPs’ knowledge and competence by chapter. Conclusions: This analysis demonstrates the success of an online CE/CME activity with micro video chapters on improving HCPs’ knowledge and competence related to the value of the multidisciplinary team members in the comprehensive care of patients receiving immunotherapy for the treatment of NMSCs. Despite these significant improvements, additional educational activities are needed to address residual gaps and further increase HCPs’ ability and comfort in providing care in this clinical setting. [Table: see text]
Characteristics, treatment patterns, and prognostic factors in small cell lung cancer transformation of advanced non-small cell lung cancer with epidermal growth factor receptor mutation after tyrosine kinase inhibitor therapy.
Authors: Ying-Ting Liao, Chi-Lu Chiang, Ruei-Lin Sun, Yi-chen Yeh, Hsu-Ching Huang, Chia-I Shen, Yen-Han Tseng, Yung-Hung Luo, Yuh-Min Chen, Jacqueline Whang-Peng
Journal: Journal of Clinical Oncology (2024)

e20569 Background: Small cell lung cancer transformation in advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation following tyrosine kinase inhibitor (TKI) therapy poses a challenging clinical scenario. This study aims to explore the characteristics, treatment patterns, and prognostic factors associated with this transformation. Methods: A total of 41 patients with transformed SCLC (tSCLC) were included. Patient characteristics, treatment details, and laboratory data were collected. Re-biopsy specimens and subsequent treatments were analyzed. Statistical analyses were conducted to identify factors associated with treatment response and survival outcomes. Results: The median age of the patients was 61.7 years old, with a median time from TKI treatment to small cell transformation of 22.2 months. The majority were female (58.5%), never smokers (80.5%), with 53.7% having stage IVB disease prior to EGFR-TKI treatment. The most prevalent initial EGFR mutation was exon 19 deletion (56.1%), and afatinib (46.3%) was the most commonly used EGFR-TKI. EGFR mutation analysis was performed in 68.3% of the tSCLC specimen, and acquired T790M was detected in 7.1% of the patients. Treatment patterns after transformation included various systemic therapies, with the most (63.4%) receiving etoposide plus platinum (EP) based chemotherapy in the first line setting. Among all the patients, 56.1% received EGFR-TKI and 22% received immune checkpoint inhibitors (ICI) throughout the post-transformation treatment course. Anemia (Hgb &lt; 10g/dL) and ever use of EP were significant factors associated with post-transformation survival. The median progression-free survival (PFS) of the first line treatment was 3.27 months, and the overall survival (OS) was 10.43 months post transformation. Conclusions: Small cell lung cancer transformation in advanced NSCLC with EGFR mutation after TKI therapy is associated with diverse clinical characteristics and dismal outcomes. We presented the complexity of managing these cases in real-world practice. Anemia and ever use of EP affected post-transformation survival. Further research is warranted to optimize therapeutic strategies for this unique subset of patients.
Hidden advertisements included in cancer information posts: Insights from social listening.
Authors: Dalyong Kim, Joo Han Lim, Wonyoung Choi, Hyun Woo Lee, Ho Young Yoon, Kyung Han You, Sang-Cheol Lee
Journal: Journal of Clinical Oncology (2024)

e21017 Background: Access to cancer information on the Internet has proliferated, yet ensuring the accuracy and reliability of such information remains a challenge. The abundance of online content necessitates a comprehensive understanding of the prevailing landscape of cancer information dissemination. Methods: Cancer-related information was retrieved from search engine results pages of NAVER and Google, the most frequently used websites for information search in South Korea, during September and October 2023. Promoted posts and overt advertisements were excluded from the dataset. Posts featuring more than 50% of advertising content were categorized as fully hidden advertisements (HA), while those with lesser proportions were classified as partially HA. In cases where there was no advertising content but the hospital name or contact information was indicated for promotional purposes, it was classified as a simple HA. Topic modeling techniques were employed to analyze the content of HA posts, identifying prevalent themes and keywords indicative of promotional intent. Results: Of the collected posts, 48.6% were classified as HA. The publisher of the HA was 26.8% of oriental medicine/care hospitals, followed by general hospitals (25.3%), non-professional (21.3%), and small and medium-sized private hospitals (17.4%). In HA, 40.3% were full advertisements, 36.75% were partial advertisements, and the remainder were simple displays. By cancer type, 65.3% of posts about breast cancer were advertising posts, 55.2% were about colon cancer, and 53.7% were about stomach cancer. In the topic modeling analysis of HA, despite containing basic and theoretical information about cancer, HA subtly directs users towards advertising content, featuring terms related to private insurance and complementary medicine. Conclusions: The study elucidates the prevalence and characteristics of HA within cancer-related information available online, highlighting the need for heightened awareness. While it may not be inherently wrong, HA can impact user perception and decision-making processes. Additional research is underway to determine whether information classified as HA can be trusted. Addressing issues such as HA within cancer information will likely require cooperation between search engine platforms and government agencies.