bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eosinophil count and immune-related adverse events (irAEs) as predictive biomarkers of survival in patients with NSCLC treated with ICIs.
Authors: Giommoni Elisa , Pillozzi Serena , Ottanelli Carlotta , Cosso Federica , Caliman Enrico , Mazzoni Francesca , Fancelli Sara , Lavacchi Daniele , Brugia Marco , Pellegrini Elisa , Vannini Agnese , Napolitano Brunella , Fuccio Sanzà Roberta , Shabani Sonia , Zepponi Francesca , Pasqui Adriano , Zenoni Andrea , Antonuzzo Lorenzo 
Published: June 2023

e21144 Background: Immune Checkpoint Inhibitors (ICIs) changed the algorithm of treatment for Non-Small Cell Lung Cancer (NSCLC). Consequently, an increased incidence of specific immune-related adverse events (irAEs) were reported, although a clear relationship between toxicity and response to ICIs was not identified. To date no strong predictive factor of response to ICIs are univocally recognized in NSCLC. Methods: This is an observational, retro-prospective, monocentric study aimed to evaluate, in patients (pts) with NSCLC treated with ICIs, the predictive impact of selected blood biomarkers and the occurrence of irAEs on survival. Differential cells count, and specifically the Absolute Eosinophil Count (AEC, N°/μL), were registered at baseline to evaluate their impact on response to ICIs. Patients were divided in two groups: those with high AEC ( > 190/µL, group A), and those with low basal AEC ( < 190/µL, group B). Results: We enrolled 48 pts, median age was 70 years. All pts were treated with an ICI as single-agent: 5 (10%) with Nivolumab (N), 37 (77%) with Pembrolizumab (P), and 5 pts received Atezolizumab (A). Thirty-seven pts were treated in first-line setting, 9 pts in second-line, and 2 pts in successive lines. Of total, 63% pts (30/48) developed at least one irAE: an endocrine event occurred in 11 pts (23%), gastrointestinal toxicity in 10 pts (21%), dermatological events in 19 pts (40%), while a pulmonary irAE in 6 pts (13%). Progression free survival (PFS) was higher in group A than in group B (16 vs 9.5, p = 0.041) with a trend for a superior median Overall Survival (mOS) (median not reached vs 23 months, p = 0.07, respectively). At a median follow-up of 18 months (mos), pts who developed at least one irAE had a significant benefit in PFS (15mos vs 8mos, p = 0.027), reporting a trend for better PFS for pts with endocrine toxicities (p = 0.057) and GI- toxicities (p = 0.051) vs no toxicities. Pulmonary irAEs are significantly related to a better PFS: median not reached vs 12 mos, p = 0.025. Conclusions: In this real-life experience we observed that baseline AEC values correlates with PFS in pts with NSCLC treated with ICIs. Additional analyses are ongoing to identify appropriate cut-offs of AEC to better stratify patients. Moreover, our study underlines that the development of toxicities, in particular pulmonary ones, could be considered as a predictive indicator of response to ICIs in NSCLC. With all the limitations of being a small analysis, our real-life experience is innovative and explored prospectively the potential role of differential cell count and irAEs as predictive biomarkers of survival in NSCLC patients treated with ICIs.
Effect of immunotherapy cessation without disease progression on outcomes in patients with metastatic non-small cell lung cancer.
Authors: McKinley Blake , Li Shenduo , Wiest Nathaniel , Butts Emily , Pai Tanmayi , Wang Jing , Mosalem Osama M , Sacchi de Camargo Correia Guilherme , Patel Jaydeepbhai , Koshiya Hiren , Inampudi Jyothik Varun , Zhao Yujie , Manochakian Rami , Lou Yanyan 
Published: June 2023

e21156 Background: Immunotherapy (IO) is one of the major treatments for patients with metastatic non-small cell lung cancer (mNSCLC). IO may be discontinued in patients for many reasons, the most common being progression of disease (POD). For those patients who discontinued IO for reasons other than POD, such as immune-related adverse event (irAE), there is limited data that compare progression-free survival (PFS) and overall survival (OS) when IO is continued vs. stopped. Methods: We conducted a retrospective study of all patients with mNSCLC (stage IV) treated with IO at our institution from 2011 to 2022. Patients who discontinued IO due to POD were excluded from the analysis. The clinical outcomes, including PFS, OS, and irAE were investigated among patients with no POD who stopped IO prior to 6 or 12 months (m) vs. those that continued IO > 6 or 12m. Results: The analysis at the 6m timepoint included 92 patients, 82.6% were white, 50% were male, 67.4% had adenocarcinoma, and 82.6% used tobacco. The most common site of metastasis was bone (28.3%), followed by CNS (20.7%). 51.2% of patients had received IO as the first line systemic therapy and 32.6% received it as their second. Pembrolizumab was the most used IO (84.78%). Among these patients, 25 discontinued IO before 6m, and 67 patients continued IO beyond 6m. irAE, of any grade, occurred in 44.0% vs 37.3% when comparing IO discontinued with IO continued group at 6m. Patients who continued treatment beyond 6m had a longer duration of PFS (22.8m vs 11.8m, p = 1.14E-04) with a significant increase in OS (34.5m vs 14.0m, p = 1.34E-07). The analysis at the 12m timepoint included 71 patients, 87.3% were white, 46.5% were male, 78.9% had adenocarcinoma, and 80.3% used tobacco. The most common site of metastasis was bone (29.9%), followed by CNS (22.5%). 62.0% of patients had received IO as the first line systemic therapy and 28.7% received it as their second. Pembrolizumab was the most used IO (87.3%). Among these patients, 30 discontinued IO before 12m, and 41 patients continued IO beyond 12m. irAE, of any grade, occurred in 36.7% vs 41.5% when comparing IO discontinued with IO continued group at 12m. Similarly, patients who continued treatment beyond 12m had a longer duration of PFS (28.4m vs 14.2m, p = 1.91E-06) with a significant increase in OS (39.9m vs 17.6m, p = 3.45E-09). Conclusions: We observed that patients with mNSCLC and no POD, who continued IO beyond 6m and 12m, experienced a significant increase in PFS and OS than those who discontinued IO, with more significant increases in those who continued IO past 12m. These findings need to be verified in a larger cohort.
Immunologic constant of rejection as a predictive biomarker of immune checkpoint inhibitors efficacy in non-small cell lung cancer.
Authors: Mogenet Alice , Greillier Laurent , Denicolai Emilie , Barlesi Fabrice , Bertucci Francois , Finetti Pascal , Tomasini Pascale 
Published: June 2023

e21162 Background: Immune checkpoint inhibitors (ICI) transformed non-small cell lung cancer (NSCLC) prognosis but response rate remains disappointing. Besides PDL1 expression, tumor mutational burden, quantification of tumor infiltrating lymphocytes or methylation profile failed to confirm their predictive role. The ICR (Immunologic Constant of Rejection) signature is defined as an immune phenotype quantifying the expression of 20 genes all involved in cancer immunity. Our first objective was the assessment of ICR signature predictive value and our secondary objectives were to compare ICR signature with other published immune signatures and to assess the prognostic value of ICR signature. Methods: Our series included 77 paraffin-embedded (FFPE) tumors derived from NSCLC patients treated with ICI as a single agent in at least the second line setting. We also collected clinical and biological data from 4 public data sets to expand and confront our local data. Transcriptomic analysis was performed using nCountertechnology Dx analysis by Nanostring based on microscopic imaging counting relative abundance of hundreds of transcripts using the “nCounter PanCancer Immune Profiling Panel” including the 20 ICR genes. Results: We applied the ICR classification to a series of 44 local tumor samples enhanced with 118 samples from public datasets. Hierarchical clustering on both local cohort and public datasets allowed us to distinguish the four ICR classes, from ICR 1 (“cold” tumors) to ICR 4 (“hot” tumors). Among the 5 datasets, we did not observe any significant difference between ICR groups for age, sex and smoking status. We observed a relative homogeneity in Durable Clinical Benefit (DCB) rate among ICR groups 2 to 4 (median DCB above 20%) unlike ICR group 1 (median DCB under 10%) leading us to consider ICR as a binary signature (ICR 1 vs ICR 2-4). ICR signature indeed showed a significant association with DCB among the 5 pooled datasets (OR = 4.40 [95% Confidence Interval 1.44-13.45] p = 0.950) with uniform distribution between them. Then, we conducted a logistic regression univariate analysis of DCB among various previously published immune signatures and ICR signature was the only one to show a significant association with DCB in this analysis ( p = 0.007). Conclusions: We identified a feasible transcriptomic signature with a promising signal of ICI efficacy prediction in the so far disappointing immune biomarkers field. In a near future, predict ICI efficacy will be a major challenge with three pivotal questions. When, balanced with the new data on ICI use in early-stage lung cancer or widely pretreated patients. How, assessing various techniques to develop composite signatures to better consider every driver of immune response. What, considering the amount of potential new therapeutic targets, starting by the 20 genes of ICR signature.
Safety, tolerability, and quality of life (QoL) of single-agent plinabulin (Plin) for the prevention of docetaxel (Doc) chemotherapy (chemo)-induced neutropenia (CIN) in non-small cell lung cancer (NSCLC) patients (pts) from two randomized trials.
Authors: Blayney Douglas W. , Legaspi Gabrielle , Duprez Stephen , Huang Lan , Mohanlal Ramon W. 
Published: June 2023

e21168 Background: Plin, is a novel, non-G-CSF, small molecule agent with comparable CIN-preventive effects vs pegfilgrastim. In contrast to pegfilgrastim, Plin is given on the same day of chemo (30 mins after chemo), and does not cause bone pain, nor thrombopenia. In the two randomized controlled (placebo (Plac)/no treatment) cancer trials, Phase (Ph) 2 Study 101 and Ph3 Study 103, single-agent (SA) Plin reduced estimated Doc-induced mean duration of severe neutropenia by > 1 Day vs Plac. We conducted a post hoc analysis of safety, tolerability, and QoL in NSCLC pts from these trials. Methods: NSCLC pts in 2nd/3rd line, with at least 1 NCCN FN risk factor, were randomized to Doc (75 mg/m2) + Plin (n = 116; at the CIN dose of 20 mg/m2 or its pharmacokinetic equivalent), or Doc + Plac (n = 296) in trials 101 (NCT00630110) and 103 (NCT02504489). Doc was given on day (D) 1, and Plin was given twice per cycle, on D1 and D8 (Plin D1 and D8 dosing is supratherapeutic for CIN but facilitated a more robust safety/tolerability evaluation [the CIN Plin dose is D1 only]). Safety blood draws and AE collection on D1 and D8; tolerability; and QoL (pre-dose and D8) were evaluated over 4 cycles. All pts received dexamethasone premedication. QoL scores were obtained in study 103 only, with Plin (n = 80) and Plac (n = 234), by validated questionnaires (EORTC QLQ C30, to evaluate global health status/QoL; the combined symptom scales/items, and the lung cancer-specific QoL questionnaire QLQ-LC13). Results: QoL scores over 4 cycles between Plin and Plac were similar, indicating Plin was well-tolerated. Grade (Gr) 3/4 AEs of interest for Plin (+Doc) and Plac (+Doc) are summarized in the table. With Plin, AE frequency of diarrhea was slightly higher (5.2% vs 1%; 1 Gr4 case with Plin), but was manageable, and so was hypertension (11.2% vs 1.7%; all Gr3 cases) vs Plac. Hypertension occurred around the time of infusion and was short-lasting (~2-4 hours) and typically self-limiting. Plin had less AEs of neutropenia (16.4% vs 50.3%) and leukopenia (15.5% vs 38.5%) vs Plac. Conclusions: Plin is an effective agent for CIN, has a favorable safety, tolerability, and QoL profile, and has the advantage of dosing on the same day of chemo. Clinical trial information: NCT02504489 . [Table: see text]
Update on real-world efficacy of anlotinib in non-small cell lung cancer.
Authors: Gao Junzhen , Xu Yan , Liu Yonggang , Liang Li , Yu Yan , Zhao Dahai , Jin Jiahui , Wang Mengzhao 
Published: June 2023

e21173 Background: Anlotinib is a novel oral small molecule TKI with anti-tumor vascular generation and growth inhibition effects, targeting VEGFR, PDGFR, FGFR, and c-kit. It has been shown to be highly effective and low toxicity in the ALTER 0303 study and was approved by NMPA in 2018 for the treatment of NSCLC(non-small cell lung cancer)as third-line and above. Previous studies have shown that anlotinib can benefit patients with advanced NSCLC, especially those in the front-line(first-/second-line). This real-world study aims to update the efficacy of anlotinib in treating NSCLC and to screen the advantage population for anlotinib treatment from front-line/back-line (third-/above-line) treatment, pathological subtype, metastasis site, gene mutation, to provide more effective anlotinib treatment strategies. Methods: This is a multicenter, retrospective, real-world study. Patients with NSCLC who have received anlotinib are included, and subgroup analysis is performed based on pathological subtypes, clinical stages, gene mutations (EGFR mutant/wildtype), front-line/back-line treatments, exploring the impact of different factors on the PFS and OS of NSCLC patients using anlotinib. Results: As of September 2022, a total of 478 patients diagnosed with NSCLC were enrolled in the study, of which 434 were evaluable, with a median age of 63 years, 263 (60.6%) were male, adenocarcinoma in 292 (67.3%), squamous cell carcinoma in 75 (17.3%). At baseline, 59 patients (13.6%) had brain metastasis, 39 (9.0%) had liver metastasis, 127 (29.3%) had bone metastasis, 194 cases (44.7%) had genetic mutations, including 135 cases (31.1%) carrying EGFR mutations. 198 patients (45.6%) received anlotinib as front-line treatment, and 236 patients (54.4%) as back-line treatment. The median follow-up time was 5.09 months (95% Cl, 2.86-7.16), with a mPFS of 4.37 months (95% Cl: 3.78-5.45) in the overall population and a mOS of 20.34 months (95% Cl: 14.88-NA). Among the 138 patients who were evaluable for efficacy, 0 cases achieved complete response (CR), 6 cases partial response (PR), and 57 cases stable disease (SD). ORR was 4.3%, and DCR was 44.9%. The mPFS of front-line was longer than the back-line (5.45 vs 3.52 months), and front-line group had a longer mOS than back-line (NR vs 16.03 months). Subgroup analysis did not find any correlations between pathological subtype or EGFR mutations and patient PFS and OS. However, it was found that the presence of liver and bone metastasis at baseline was related to a shorter OS with anlotinib in the back-line (8.28 vs 16.23 months, p = 0.0253; 7.89 months vs NR, p < 0.001). Conclusions: Anlotinib shows well efficacy in NSCLC patients, prolonging progression-free survival (PFS) and overall survival (OS), especially for front-line patients, suggesting that these patients may be a preferred population for using anlotinib, providing effective evidence for the use of anlotinib treatment for NSCLC patients.
Correlation of drug susceptibility testing on short term cultures of CTCs positively with clinical outcomes in non-small cell lung cancer.
Authors: Kumar Prashant , Limaye Sewanti Atul , Kanakasetty Govind Babu , Balakrishnan Ajay , Joshi Asim , Govindan Sindhu , Venkataramanan R , Kuriakose Moni 
Published: June 2023

e21177 Background: Enumeration of circulating tumor cells (CTCs) is rapidly emerging as a minimally invasive and reliable technique for monitoring disease progression and patient’s response to treatment. However, its utility beyond enumeration in clinical management of cancer remains scarcely explored. Being biologically similar to both primary and secondary tumors, CTCs may help in identification of most efficacious therapies. In this study, we propose a method for short term culture of CTCs thereby allowing to evaluate the drug susceptibility testing in individual patients. Methods: We obtained peripheral blood samples from 20 advanced stage lung cancer patients undergoing treatment at Kidwai Memorial Institute of Oncology, Bangalore, India. These blood samples were processed and cultured on ellipsoidal microwells maintained at hypoxic conditions (1% O2). The CTC clusters were seeded onto 96 well plates coated with Matrigel and treated with the same drug regimen as the respective patients. The viability of the cells was measured using CellTitre-Glo. Results: Of the 20 samples, tight cluster formation was observed in four samples and drug susceptibility testing was performed. Based on clinical treatment received, we treated CTCs with combination of pemetrexed and carboplatin at respective Cmax concentrations of 5.68 and 3.68 µg/ml. The combination drug treatment resulted in decreased viability of CTCs to 30.7%. Notably, the CT scan images demonstrated significant reduction of pleural effusion in patient following treatment with carboplatin and pemetrexed, thus correlating with our in vitro drug susceptibility finding. Conclusions: In this proof of concept study, we demonstrate the feasibility of utilizing in vitro drug susceptibility testing on CTCs as an approach to guide patient specific chemotherapeutic treatment approaches, thus opening avenues for personalized treatments.
Auranofin and the efficacy of anti-PD1 immunotherapy.
Authors: Zhang Yan 
Published: June 2023

e21180 Background: Anti-PD-1 immunotherapy brings hope for the treatment of malignant tumors, but its overall response rate is low.Therefore, how to sensitize anti-PD-1 therapy to make more patients benefit from immunotherapy is an urgent clinical demand. Methods: PKCι, as a classical oncogenic gene that affects cell proliferation and differentiation, has recently been found to participate in the formation of tumor immunosuppressive microenvironment (TIME). TIME directly leads to resistance to anti-PD1 therapy, so by inhibiting the expression of PKCι to regulate the inhibitory tumor immune microenvironment and sensitize anti-PD1 therapy. Auranofin is a commonly used anti-inflammatory drug in clinic. Recently, it was found that it can inhibit the expression of PKCι and retard growth of tumor. Results: Our study found that interference with PKCι expression in tumor cells can reverse the immunosuppressive microenvironment and enhance the effect of anti-PD1 therapy. Auranofin (PKCι inhibitor) combined with anti-PD-1 immunotherapy has better anti-tumor effect than single drug therapy. Auranofin can inhibit the expression of PKCι and its downstream YAP1 and TNFα, reduce the recruitment of immunosuppressive cells such as MDSCs and Treg, promote the infiltration of effector T cells, ultimately reverse the inhibitory immune microenvironment and play a synergistic anti-tumor role. Conclusions: In summary, the combination of Auranofin and anti-PD-1 immunotherapy can reverse the TIME to sensitize the immune effect, play a synergistic anti-tumor effect, and provide a new idea and theoretical basis for immunotherapy of malignant tumors.
Long-term survival following adrenalectomy for secondary adrenal tumor (SATs): A systematic literature review and meta-analysis.
Authors: Alhajahjeh Abdulrahman Ahmad , Kong Joshua , Odisho Tanya , Maqsood Hannan Ahmad , Al-Share Bayan A , Shahait Awni , Shahait Mohammed 
Published: June 2023

e21181 Background: Secondary Adrenal tumors (SATs) are uncommon forms of cancer that occur as a result of metastasis from primary tumors (PT) elsewhere. A systemic review and metanalysis was conducted to assess characteristics and survival following adrenalectomy for SATs. Methods: A systematic literature search was performed (01/1990-12/2022) using several databases (PubMed, Embase, the Cochrane Library, the ASCO library). The inclusion criteria included a known previous PT and confirmed isolated adrenal metastasis either by biopsy or serial imaging (synchronous or metachronous) in patients who underwent adrenalectomy. The primary outcome of interest was the overall survival (OS) of patients following adrenalectomy of SAT. Metanalysis of pooled survival curves for OS was completed, and KM curves were used to create pseudo-individual patient data. Results: A total of 29 studies were analyzed, including 2,401 patients with SAT most of which underwent adrenalectomy. The average age of the group was 60.8 ±3.54years. Lung cancer was the most common PT (33.3%), followed by renal cancer (24.7%). About two thirds (67.7%) of patients had isolated metastasis. The average time from PT diagnosis to adrenal metastasis was 22.4 ±11.11 months. Data of 1,712 patients were used to estimate the combined 5-year OS. The median OS was 35.7 months [95% Confidence interval (CI): 29.1 - 50.4]. One, three, and five-year OS were 80.9% [95% CI: 75.6 - 84.6], 49.6% [95% CI: 43.4 - 56.8], and 38.2% [95% CI: 32.2 - 44.5], respectively. Conclusions: The results of this metanalysis and systematic literature review provide insight into the long-term survival of patients with secondary adrenal tumors who underwent adrenalectomy. The study highlights the need for further research to identify the risk factors that play a role in the clinical outcome of adrenalectomy in patients with adrenal metastasis.