bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isatuximab plus carfilzomib and dexamethasone in east Asian patients with relapsed multiple myeloma: IKEMA subgroup analysis.
Authors: Kim Kihyun , Min Chang Ki , Koh Youngil , Ishizawa Kenichi , Kim Sung-Hyun , Ito Shigeki , Junji Tanaka , Uchiyama Michihiro , Kawano Yawara , Kim Jin Seok , Moreau Philippe , Martin Thomas G. , Dong Yvonne , Risse Marie-Laure , Suzuki Kenshi 
Published: June 2021

e20015 Background: The Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) plus carfilzomib and dexamethasone (Kd) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed multiple myeloma (RMM) (hazard ratio [HR] 0.53; 99% confidence interval [CI] 0.32–0.89; P= 0.0007). We evaluated the efficacy and safety of Isa-Kd in the East Asian patients (19 Japanese, 27 Korean). Methods: RMM pts who received 1-3 prior lines of therapy were stratified to receive Isa-Kd or Kd. Isa-Kd arm received Isa (10 mg/kg intravenously) weekly for 4 weeks, then every 2 weeks. Both arms received K (20 mg/m2 days 1-2, 56 mg/m2 thereafter) twice-weekly for 3 of 4 weeks, and d (20 mg) twice-weekly. Treatment continued until disease progression or unacceptable adverse events (AE). The primary endpoint was prolongation of PFS. Key secondary endpoints included; very good partial response or better (≥VGPR), complete response (CR) rate and minimal residual disease negativity (MRD–) rate. Results: East Asian pts (25 Isa-Kd, 21 Kd) were randomized. Pt characteristics were similar in the East Asian subgroup compared with the intent to treat (ITT) population (N = 302). Median age (Isa-Kd 64.0 [range 45–83] years vs Kd 60.0 [range 33–73] years); median prior lines Isa-Kd 2.0 (range 1–3) vs Kd 1.0 (range 1–3); refractory to lenalidomide 16.0% Isa-Kd vs 47.6% Kd; refractory to PI 20.0% Isa-Kd vs 33.3% Kd; high-risk cytogenetics 48.0% Isa-Kd vs 42.9% Kd. After a median follow-up of 20.7 months, the addition of Isa to Kd improved ≥VGPR, CR and MRD– rates (Table). The HR 0.64 (95%CI: 0.231-1.764) for disease progression or death favored Isa-Kd. Grade ≥3 AEs were observed in 79.2% Isa-Kd vs 55.0% Kd pts, serious TEAEs in 45.8% Isa-Kd vs 50.0% Kd; TEAEs leading to treatment discontinuation were lower in the Isa-Kd group (4.2% Isa-Kd vs 10.0% Kd). Overall, 64.0% Isa-Kd vs 42.9% Kd pts were still receiving treatment. Conclusions: Efficacy and safety results of Isa-Kd in East Asian pts are consistent with the results of the overall IKEMA population, in which significantly better efficacy (PFS, CR, ≥VGPR and MRD– rate) was reported in favor of Isa-Kd without an increase in the number of patients with serious TEAEs or discontinuations. Isa-Kd is a potential treatment option for East Asian pts with RMM. Clinical trial information: NCT03275285. [Table: see text]
Distinct clinical characteristics and prognosis of ground-glass opacity-type lung cancer: A systematic review and meta-analysis.
Authors: Chongxi Ren , Ruisheng Yin , Hongqiao Wang , Hongchen Wang , Tong Zhou , Fengying Li , Xin Wang , Meng Li , Hongxia Qi , Sheng Li , Haixia Ren , Xuefeng Li , Fengyan Li , Juan Wang , Fengshuo Yang 
Published: June 2021

e20505 Background: Lung ground-glass opacity (GGO), a hazy increased opacity on computed tomography with preservation of bronchial and vascular margins, has been shown to be associated with early-stage lung cancer. With the increasing prevalence of ground-glass opacity-type lung cancer (GGO-LC), more researches have focused on the diagnosis and treatment of this early stage lung cancer; however, the clinical characteristics and survival outcomes of this disease has not yet been fully elucidated. Aim: To analyze and review the clinicopathological characteristics for GGO-LC and to identify the optimal treatment strategies in this select population. A systematic review and meta-analysis of the literature were carried out. The study was registered (CRD42021228774). Methods: We did a systematic review and meta-analysis of observational studies published from database inception to June 30, 2020, which reported on clinicopathological characteristics, management and survival outcomes in patients with GGO-LC. Studies were identified by searches in PubMed, MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and by hand searching of previous publications. We extracted the general information to perform the meta-analysis, mainly focusing on age, gender, and smoking status. We also extracted treatment and prognosis information to assess the effect of treatment strategies on overall survival (OS). Robustness of pooled estimates from random-effects models was considered with sensitivity analyses, meta-regression, and subgroup analyses. All statistical analyses were performed with Stata 16.0. Results: Data on 9444 patients in 27 observational studies were included. GGO-type lung cancer was typically characterized as non-invasively or minimally invasively low-grade adenocarcinomas. Therapeutic intervention for these early stage lung cancers was an important opportunity for decreasing overall mortality of lung cancer. The final pooled analysis showed that the average age at diagnosis, female proportion and non-smoking proportion of patients with GGO-LC was 57.7 (95% CI, 53.9-61.5, P < 0.001, I2 = 92.9%), 0.591 (95% CI, 0.563-0.619, P < 0.001, I2 = 86.7%), and 0.631 (95% CI, 0.556-0.706, P < 0.001, I2 = 98.3%), respectively. The pooled overall survival rate was 96.2% (95% CI, 0.954 to 0.970, P < 0.001, I2 = 78.9%). The results showed that the majority of GGO-LC patients had good survival outcomes, presenting a significant proportion of young, female and non-or light smokers. Conclusions: From our analysis, it demonstrates that the patients with GGO-LC may be relatively young females and non-or light smoking history, and had better prognosis. However, there are some limitations in the present study, and more evidence is necessary to wait for more results from RCT to draw a valid conclusion.
Does multiplicity of synchronous multiple lung primaries (SMLPs) affect prognosis.
Authors: Xue RuoBing , Maharaj Satish , Kumar Rohit , Kloecker Goetz H. 
Published: June 2021

e20530 Background: SMLPs are detected more commonly due to advancements in screening technology. Their workup and classification; however, are still lacking a clear standard. T stage of the largest lesion has been used as the major prognostic marker. This; however, does not take the number of SMLPs and their genomic drivers into consideration. This study aims to identify and review common risk factors associated with SMLPs and determine whether the number of primaries influence the prognosis. Methods: A systematic review of the literature published between 2000 and 2021 was conducted through PubMed and Medline by using the combination of keywords, including: “synchronous multiple primary lung cancer”, “simultaneous multifocal lung cancer”, “synchronous solitary lung metastasis”, “risk factor” and “prognosis”. A total of fifty studies were identified, among them only sixteen retrospective research articles and two review articles were relevant to the study at hand. Results: Sixteen retrospective studies including a total of 1685 eligible patients were reviewed. Thirteen of these studies reported the main histology type to be adenocarcinoma with a ratio ranging from 35% to 96.8%. Eight studies have reported the numbers of synchronous primary lung cancers, including one study found 11 SMLPs. Among these, one study by van Rens found number of SMLPs impact prognosis adversely compared to a single lung cancer. However, three other studies demonstrated multiple SMPLs do not adversely affect survival (Finley et al, 2010; Kocaturk et al, 2011; Li et al, 2020). Four of the sixteen studies analysed the effect of multiple lobes involvement and distance between tumors, with varying conclusions; two studies reported no difference in prognosis while one study revealed worse survival with multiple lobe involvement and one study found favorable outcome. Most studies confirm the usual prognostic factors for SMLPs, including: gender, smoking, type of surgery, comorbidities and adjuvant therapy. The median 5 year OS reported for SMLPs is 66%, with a wide range from 19% to 95.8%.The 3 year OS is 75% in most studies. Conclusions: The data on how the number of SMLPs affects the prognosis is uncertain. The current recommendation to base the decision for adjuvant therapy on the highest T stage is not supported by prospective evidence or consistent among published case series. Considering the recent approval of targeted therapies in early stage lung cancers, a better prognostic scoring system for SMLPs is required.
Concurrent chemoradiotherapy with weekly cisplatin in stage III unresectable non-small cell lung cancer (NSCLC): A local experience with LATAM patients.
Authors: Salinas Carlos , Pinto Negrete Felipe Eduardo , Saavedra Maria Paz , Orlandi Francisco J 
Published: June 2021

e20535 Background: Lung cancer is the leading cause of cancer related death worldwide and so is expected in Chile in 2021 accoding to Globocan, with a 12.4% mortality rate last year. Among NSCLC, 35 to 40% present as locally advanced disease, most of them non surgical candidates. Current standard of treatment is platinum-based doublet with concurrent Radiotherapy plus adyuvant durvalumab since 2018. Still many controversies related to different approaches are not settled. Few literature is available concerning a less aggressive approach in order to achieve a more tolerable treatment for the patient preserving effectiveness. Many patients compromise the treatment compliance due to early toxicities. We present our preliminary results of local data consisting in weekly cisplatin plus concurrent standard dose of radiotherapy. Methods: We performed a retrospective review of local database for stage III unresectable NSCLC between 2013 to 2019. Baseline clinical data , treatment modality, toxicities and response rates were recorded for all patients. Outcomes were analyzed by measuring overall response rate (ORR) , progression free (PFS) and overall survival (OS). Toxicities were assessed by CTCAE v5.0 and treatment response by RECIST 1.1 criteria. Results: 54% of the patients were men, 68%ECOG 0 and 32% ECOG 1. Mean BMI of 26 kg / m2. 100% smokers with average 39 packages per year and 71% had some other comorbidity;. 26% had emphysema. Histologic confirmation of 74%adenocarcinom and as. 26% squamous cell carcinoma. Staging analysis showed 23% stage IIIA, 54% stage IIIB, and 23% stage IIIC. Only 6 patients received adjuvant treatment before being diagnosed with stage III disease. Chemoradiotherapy is carried out as follows: 86% cisplatin (median 54.4 mg/m2) as a single weekly dose combined with standard radiotherapy of 60 Gy /30 Fr in a concurrent modality in ???. 74.2% completed follow up after CRT and the remaining 50% received adyuvant durvalumab. 71% of the patients reported some degree (mild, moderate or severe?) of toxicity related to the treatment; 37.1% grade 2 actinic pneumonitis, 11.4% grade 2 actinic esophagitis and 11.4% grade 1 acute renal failure among the most significant. No CTCAE 5.0 grade 4 and 5 toxicities were reported. 82.8% progressed in 15 months average (mean??); with 17% with current stable disease. The ORR was 48,5%. The mOS was 23 months (95% CI [16,7-29,3]) and the mPFS was 10 months (95% CI [8.25-11.75]. Conclusions: Since PACIFIC trial, stage III unresectable NSCLC have experienced a pivotal change in management. Unfortunately, our Public Health Insurance System does not cover access for all pts. This approach reaches similar results described in earlier trials published in the area and could be an option in certain clinical settings.
Incidence of pneumonitis among limited-stage small cell lung cancer patients exposed to concurrent chemoradiation: A systematic literature review and meta-analysis.
Authors: Zu Ke (Kirsten) , Kuang Yuting , Nevo Arianna , Pietanza Maria Catherine , Liu Mike , Deitz Anne , Uyei Jennifer , Darpan Darpan 
Published: June 2021

e20592 Background: Concurrent chemoradiation (cCRT) has been the standard first line treatment for patients with limited-stage small cell lung cancer (LS-SCLC) for decades. Despite continued progress in refining chemotherapy and radiation modalities, the prognosis for LS-SCLC remains unsatisfactory with cCRT alone. Recent clinical trials have sought to further improve survival by combining cCRT and other newly developed therapeutic agents in treating LS-SCLC. Severe (grade 3 or higher) pneumonitis is one of the major toxicities related to cCRT. The objective of this study was to establish a benchmark rate of pneumonitis in LS-SCLC patients receiving first line cCRT. Methods: A systematic literature review and meta-analysis was performed in accordance with Cochrane, PRISMA, and Food and Drug Administration guidelines to summarize and quantify the incidence of grade 3−5 and fatal pneumonitis (including radiation pneumonitis) in patients with LS-SCLC exposed to cCRT alone. MEDLINE, Embase, and the Cochrane Central Register were searched from 2014 to July 16, 2020 to identify relevant randomized controlled trials (RCTs) and non-RCT studies (observational studies or non-randomized trials). The study quality of included RCTs and non-RCT studies was evaluated using the Revised Cochrane Risk of Bias Tool for Randomized Trials (RoB2) and the Newcastle-Ottawa scale, respectively. The incidence of pneumonitis across studies was pooled using a frequentist method with correction for zero events, using the metafor package in R 3.6.1. Results: Thirteen studies (4 RCTs, 9 non-RCTs) were included in the review. Patient populations were comparable across studies and the median follow-up ranged from 20−59 months. All patients received etoposide with either cisplatin or carboplatin, and radiation doses, given once or twice daily, ranging from 40−72 Gy. While all RCTs were open-label studies that could have some deviations from the intended interventions, this did not impact the reported incidence of pneumonitis. All non-RCTs were of high quality. Ten studies were included in the meta-analysis (3 RCTs, 7 non-RCTs; 1,539 patients). The pooled incidence of grade 3−5 pneumonitis was 3.28% [95% confidence interval (CI): 1.52−5.04%] in RCTs from random-effects model, and 6.34% [95% CI: 3.64−9.04%] in non-RCTs from fixed-effects model. The pooled incidence risk of grade 5 (fatal) pneumonitis was 0.29% [95% CI: 0.00−0.62%] in RCTs and 0.88% [95% CI: 0.02−1.74%] in non-RCTs, both from fixed-effects model. Conclusions: In LS-SCLC patients exposed to cCRT, the incidence of grade 3−5 pneumonitis and fatal pneumonitis ranges from 3.28−6.34% and 0.29−0.88%, respectively. These results can be used to understand the safety of other therapeutic agents with regard to pneumonitis when used in combination with cCRT to treat patients with LS-SCLC.
Distinct subset of immune cells assessed by multiplex immunohistochemistry correlates with immune phenotype classified by an artificial intelligence-powered tissue analyzer in advanced non-small cell lung cancer.
Authors: Choi Yoon-La , Park Sehhoon , Pereira Sergio , Park Seonwook , Ma Minuk , Shin Jiwon , Shin Jisoo , Paeng Kyunghyun , Yoo Donggeun , Ock Chan-Young , Lee Se-Hoon 
Published: June 2021

e21012 Background: Pathologic classification of immune phenotype is challenging since there is no consensus on how to assess spatial relations of tumor-infiltrating lymphocyte (TIL) on cancer epithelium (CE) and cancer stroma (CS) in whole-slide images (WSI). We previously suggested that the artificial intelligence (AI)-powered tissue analyzer, Lunit SCOPE IO, can classify immune phenotype, and that its predictions are correlated with the clinical outcome of immune checkpoint inhibitor (ICI) in non-small cell lung cancer (NSCLC). In this study, we designed a pathologic validation of immune phenotype using multiplex immunohistochemistry. Methods: Lunit SCOPE IO was developed based on a 2.8 x 109 micrometer2 area of CE or CS, and 5.9 x 106 TILs from 3,166 H&E Whole-Slide Image (WSI) of multiple cancer types, annotated by board-certified pathologists. H&E WSIs were divided into 1 mm2-sized tiles, where we classified immune phenotype (IP) based on TIL density on CE and TIL density on CS. Representative IP was determined based on the overall proportion of tile-level IPs in each WSI. Multiplex immunohistochemistry (mIHC) staining with CD3, CD8, CD20, CD68, FOXP3, CK, and DAPI was performed in NSCLC tumor tissues (n = 99) treated with immune checkpoint inhibitors (ICI) at the Samsung Medical Center. A normalized number of cells expressing each marker was calculated by dividing the total number of marker-positive cells by the number of DAPI-positive cells in each WSI. Results: The proportions of inflamed IP, immune-excluded IP, and immune desert IP in the analysis set were 46.5%, 29.3%, and 24.2%. respectively. Median progression-free survival of ICI was 6.4 m in inflamed IP, 1.9 m in immune-excluded IP, and 1.6 m in immune-desert IP (hazard ratio of inflamed versus others: 0.43, confidence interval 0.27-0.68, P = 0.000188). Multiplex IHC results showed that the normalized CD3-positive cells and CD8-positive cells, which play a role of anti-tumor activity, were highly enriched in inflamed IP compared to those in other IPs (CD3: fold change [FC] 1.57, P = 0.0182; CD8: FC 1.24, P = 0.0697), whereas FOXP3-positive cells, linked to the immunosuppressive activity, were enriched in immune-excluded IP (FC 1.26, P = 0.0656). We also noted that CD68-positive cells were significantly enriched in immune-desert IP (FC 1.76, P = 0.00467). Conclusions: The immune cell subset in WSI is distinct according to the immune phenotype, as CD3- or CD8-positive cells are enriched in inflamed IP rather than immune-excluded IP as classified by AI-powered TIL analysis of H&E image.
Patient-derived lung cancer organoids for the selection of therapeutic options in an ALK-rearranged tumor.
Authors: Jimenez Munarriz Beatriz , Dantes Zahra , De Castro Javier , Navarro Paloma , Yagüe Monica , Barquin Arantzazu , Rodriguez-Moreno Juan Francisco , Sevillano Elena , Ruiz Sergio , del Barrio Anabel , Ledo Gema García , Dorta Miriam , Lorduy Ana Collazo , Calvo Emiliano , García-Donas Jesús , Serrano Sandra , Manjunath Apoorva , Ferreira Luciana , Hefel Barbara , Remon Jordi 
Published: June 2021

e21014 Background: ALK rearrangements are key targets in non-small-cell lung cancer (NSCLC). Unfortunately, the optimal sequential strategy of ALK-tyrosine kinase inhibitors (TKI) remains to be defined. Testing drug sensitivity in patient derived organoids (PDOs) could support a rational drug selection in this setting. Methods: We designed an observational study assessing the correlation between drug sensitivity of PDOs established in Invitrocue and the clinical outcome in our institution. To date, forty cases have been included, of which nine were lung cancers. Results: PDO was sucessfully established in 7/9 cases (77%). Three patients did not receive any of the drugs tested in vitro due to clinical deterioration. One patient was deemed as sensitive to carboplatin but tumor showed to be resistant. A meaningful correlation was observed in an oncogenic addicted tumor. A 54-year-old never-smoker man who had been diagnosed with lung adenocarcinoma stage IVa (T3N1M1a). He received standard first-line therapy with platinum-based chemotherapy, immunotherapy and antiangiogenics achieving tumor progression. A next-generation sequencing (NGS) panel revealed the presence of the EML4-ALK fusion variant 3a/b. The patient started alectinib but showed progression after 12 months. A second NGS panel did not identify any new ALK resistance mutation but acquiring TP53. Treatment was switched to brigatinib with no response. Finally, fresh tumor tissue was obtained from a liver biopsy to establish PDOs and drug sensitivity to 8 compounds was tested. The In vitro results demonstrated no activity of lorlatinib but a strong response to crizotinib. The patient started Crizotinib 250mg BID achieving partial response after 8 weeks and treatment duration of 6 months. A third liver biopsy for PDOs and NGS revealed acquired ALK C1156Y and I1171T mutations that confer resistance to crizotinib but sensitive to ceritinib, respectively. Conclusions: We present clinical evidence that PDOs are an alternative tool in oncogenic addicted tumors helping to guide treatment decisions and increasing a more personalized sequential treatment approach.
Prospective correlation between the patient microbiome with response to and development of immune-mediated adverse effects to immunotherapy in lung cancer.
Authors: Chau Justin , Yadav Meeta , Liu Ben , Furqan Muhammad , Dai Qun , Shahi Shailesh , Gupta Arnav , Nace Mercer Keri , Eastman Evan , Abu Hejleh Taher , Chan Carlos Hou Fai , Weiner George J. , Cherwin Catherine , Lee Sonny T.M. , Zhong Cuncong , Mangalam Ashutosh , Zhang Jun 
Published: June 2021

e21024 Background: Though the gut microbiome has been associated with immunotherapy (ICI) efficacy in certain cancers, similar correlations between microbiomes at other body sites with treatment response and immune related adverse events (irAEs) in lung cancer (LC) patients receiving ICIs have not been made. We designed a prospective cohort study conducted from 2018-2020 at a single-center academic institution to assess for correlations between the microbiome in various body sites with treatment response and development of irAEs in LC patients treated with ICIs. Methods: Patients with histopathologically confirmed, unresectable/advanced/metastatic LC planned to undergo ICI-based therapy were enrolled between September 2018 and June 2019. Patients must have had measurable disease, ECOG 0-2, and good organ function to be included. Data was collected for analysis from January 2019 to October 2020. Nasal, buccal and gut microbiome samples were obtained prior to ICI initiation, at development of irAEs, improvement of irAEs to grade 1 or less, and at disease progression. 16S rRNA sequenced data was mapped to the SILVA 13.2 database; operational taxonomic unit clusters were analyzed using MicrobiomeAnalyst and METAGENassist. Results: 37 patients were enrolled, and 34 patients were evaluable for this report. 32 healthy controls (HC) from the same geographic region were included to compare baseline gut microbiota. Compared to HC, LC gut microbiota exhibited significantly lower α-diversity. The gut microbiome of patients who did not suffer irAEs were found to have relative enrichment of Bifidobacterium ( p = 0.001) and Desulfovibrio ( p = 0.0002). Responders to combined chemoimmunotherapy exhibited increased Clostridiales ( p = 0.018) but reduced Rikenellaceae ( p = 0.016). In responders to chemoimmunotherapy we also observed enrichment of Finegoldia in nasal microbiome, and increased Megasphaera but reduced Actinobacillus in buccal samples. Longitudinal samples exhibited a trend of α-diversity and certain microbial changes during the development and resolution of irAEs. Conclusions: This pilot study identified significant differences in the gut microbiome between HC and LC patients, and correlates specific bacterial genera to ICI response and irAEs in LC. In addition, it suggests potential predictive utility in nasal and buccal microbiomes, warranting further validation with a larger cohort and mechanistic dissection using preclinical models. Clinical trial information: NCT03688347.