tbuckley/cabot-search huggingface dataset:
Lenvatinib plus pembrolizumab versus lenvatinib in patients with unresectable hepatocellular carcinoma: A real world study.
Authors: I-Cheng Lee, Chi-Jung Wu, San-Chi Chen, Yee Chao, Yi-Hsiang Huang
Journal: Journal of Clinical Oncology (2021)

e16138 Background: The combination of lenvatinib (LEN) and pembrolizumab (PEMBRO) showed promising response rates and survival in a phase 1b trial for patients with unresectable hepatocellular carcinoma (HCC). Whether LEN plus PEMBRO provides better outcomes than LEN monotherapy remains unclear. The aim of this study was to compare the outcomes of LEN plus PEMBRO versus lenvatinib monotherapy in patients with unresectable HCC in the real world setting. Methods: A total of 123 patients with unresectable HCC were retrospectively enrolled, including 61 patients with LEN monotherapy and 62 patients with LEN plus PEMBRO. We evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) by RECIST 1.1 and modified RECIST (mRECIST) criteria. Results: One hundred and one (82.1%) patients were in BCLC stage C and 81 (65.9%) patients received LEN or LEN plus PEMBRO as first line setting. During a median follow-up period of 8.0 months, 71 (57.7%) and 31 (25.2%) of patients had disease progression and death, respectively. The median PFS was 8.4 and 4.9 months in the LEN plus PEMBRO and LEN monotherapy groups, respectively (p = 0.033). The median OS was not reached in the LEN-PEM group and was 17.2 months in the LEN monotherapy group (p = 0.064). Patients with LEN plus PEMBRO had higher objective response rate (ORR: 34.4% vs 23.7% by RECIST 1.1, p = 0.277; 57.4% vs 32.2% by mRECIST, p = 0.010) and higher disease control rate (83.6% vs 62.7% by RECIST 1.1, p = 0.017; 85.2% vs 62.7% by mRECIST, p = 0.009). In subgroup patients with BCLC stage C, LEN plus PEMBRO provided significantly longer PFS (9.1 vs 4.8 months, p = 0.008), higher ORR (60% vs 33.3%, p = 0.015) and higher DCR (88% vs 60.4%, p = 0.004) by mRECIST criteria. Conclusions: LEN plus PEMBRO provides significantly better ORR, DCR and PFS then LEN monotherapy for patients with unresectable HCC.
Minimal residual disease (MRD) in patients with resected stage I NSCLC: Results of the prospective adjuvant IFCT-0703 trial.
Authors: Damien Vasseur, Cécile Jovelet, Nathalie Cozic, Julien Mazieres, Fabrice Barlesi, Jaafar Bennouna, Radj Gervais, Lionel Moreau, Henri Berard, Olivier Molinier, Denis Moro-Sibilot, Pierre Jean Souquet, Elodie Amour, Franck Morin, Gerard Zalcman, Jean-Charles Soria, Virginie Westeel, Ludovic Lacroix, Benjamin Besse
Journal: Journal of Clinical Oncology (2021)

8526 Background: MRD aims to detect circulating biomarkers of micrometastatic disease and ultimately predict recurrences. The IFCT-0703 randomized phase II trial failed to show a benefit of 6 months adjuvant pazopanib (P) vs. placebo after resection of stage I NSCLC (7th TNM edition). The outcome of pts based on their MRD status has been evaluated. Methods: Blood samples were collected in EDTA tubes (Becton Dickinson Company) after surgery (T0), after 3 months (T3) of P or placebo and at the end of treatment (T6). Plasmas were obtained after double centrifugation of total blood. Total nucleic acid was extracted using the Maxwell RSC LV plasma kit (Promega) according to the manufacturer’s protocol. Samples were quantified using the QuBit dsDNA HS Assay kit on a QuBit 3.0 flurometer (Thermo Fisher Scientific). Molecular analysis was performed by next generation sequencing using the Oncomine Lung cfDNA Assay (ThermoFisher Scientific). Two MRD definitions were tested : 1) high level of DNA in the blood or 2) any mutation detected by the standard bioinformatic pipeline was considered present, whatever the allelic fraction. Results: 143 pts were randomized in 29 centers between March 2009 and August 2012, 71 and 72 in the placebo and P arms respectively. Among the 119 pts with evaluable T0 samples, 27 pts recurred and 14 died. Median DNA concentration ([DNA]) was 6.6 ng/ml and an increase of [DNA] of 10 ng/ml was found prognostic of poor DFS and OS, HR=1.4, 95%CI [1.14-1.72], p=0.0016 and HR=1.62, 95%CI [1.15-2.30], p=0.0057 respectively. In 81 pts with available T0-T6 samples, [DNA] variation had no different impact on DFS and OS, in the P arm and the placebo arm. ctDNA mutations (ctDNA+) were detected in 31/119 pts. ctDNA+ were more frequent in samples with high DNA quantity (p=0.0002). Genes mutated at T0 were TP53 in 16, NRAS in 6, MAP2K1 in 2, KRAS in 1, EGFR in 5, BRAF in 1, ALK in 2. 29 pts had 1 mutation, 2 had 2 mutations. DFS and OS were similar between pts with or without ctDNA+ : HR= 1.038 (95%CI 0.438-2.456, p=0.93) and 1.193 (95% CI 0.367-3.882, p=0.77) respectively. Among 27 pts with ctDNA+ at T0 and available sample at T6, 23 had no more mutations at T6. Two pts had a ctDNA+ only at T6 (not at T3), one of them had a recurrence at 7 months. Conclusions: Post-operative ctDNA mutations are found in 26.0% of the pts but their positivity had no impact on DFS or OS. In contrast, DFS and OS were poorer in pts with increased plasma DNA concentration. ctDNA mutations status do not recapitulate the complexity of MRD characterization. NGS will be performed on matched tissues in order to refine MRD definition. Clinical trial information: NCT00775307.
Overall survival differences between women and men with leiomyosarcomas.
Authors: Ashna Wadhawan, Arjun Khunger, Shenae Samuels, Jianli Niu, Jorge Adames, Candice Sareli, Luis E. Raez, Matthew Philip Salzberg, Michel Vulfovich, Atif Mahmoud Hussein
Journal: Journal of Clinical Oncology (2021)

e17562 Background: Leiomyosarcomas (LMS) are one of the most frequently occurring subtypes of soft tissue sarcomas and are associated with poor prognosis and high risk of recurrence even in the early stages of the disease. Primary management involves surgical excision followed by chemotherapy for all stages. We sought to determine the prognostic factors on associated with leiomyosarcoma survival. Methods: The National Cancer Database from 2004-2016 was utilized to obtain demographics, tumor characteristics and treatment factors of LMS. LMS was divided into three groups for analysis- women with uterine LMS, women with ex-uterine LMS and men with LMS. Univariate and backward stepwise multivariate logistic regression models were used to determine prognostic factors associated with long-term survival in each group. Kaplan-Meier method with log rank test was used to compare overall survival (OS) rates among the three groups. Results: A total of 23194 patients were identified. Only 18.7% of men with LMS utilized chemotherapy as compared to 47.4% women with uterine and 25.0% with ex-uterine LMS. Both men and women had comparable palliative care use- 3.9% in women with uterine LMS, 3.5% in women with ex-uterine LMS and 3.0% in men with LMS. There were statistically significant differences (P=0.000) between overall survival among the three groups. Median OS was highest among men with LMS (72m) followed by women with ex-uterine LMS (57.2m) and women with uterine LMS (36.7 m). On multivariate analysis, in women with uterine LMS, increasing age (OR =0.95, P=0.018), presence of lymphovascular invasion (OR=0.25, P=0.000) were associated with decrease in the likelihood of survival. In women with ex-uterine LMS, increasing age (OR=0.97, P=0.000), increasing stage (I-IV) (OR=0.56, P=0.000), presence of tumor (OR=0.39, P=0.001), those with residual tumor and surgical margins (OR=0.87, P=0.009), and patients who received systemic therapy and surgery (OR= 0.85, P=.0016) had a reduced likelihood of survival. In men with LMS, factors such as increasing age (OR=0.96, P=0.000), increasing number of regional lymph nodes (OR=0.91, P=0.027), having had a surgical diagnostic or staging procedure (OR= 0.69, P=0.004), increasing stage (OR = 0.64, P=0.005), and residual tumor or margins (OR=-0.76, P=0.013) were associated with reduced likelihood of survival. Results also suggest that increasing year of diagnosis was associated with an increased likelihood of survival (OR=1.51; P=0.000). Conclusions: Women were found to comprise almost two third of the patient population with LMS. Men were found to have longer survival than women with LMS, despite low utilization of chemotherapy. It may be due to poor prognosis of LMS in the female reproductive organs while LMS in the extremities has better prognosis. Future prospective trials should stratify based on sex and in women location.
Disparities in cancer prevalence in African Americans: A United States population study 2021.
Authors: Ahmad Nader Kassem, Akram Alkrekshi, Raul Arroyo Suarez
Journal: Journal of Clinical Oncology (2021)

6531 Background: African-Americans (AA) have the highest incidence and death rates from cancer and the shortest survival of all racial groups in the USA, as reiterated by the American Cancer Society’s Cancer Facts and Figures for AA from 2019. We studied cancer prevalence in AA compared to Caucasians, focusing on patients with above-normal Body Mass Index (BMI). Methods: Data was collected from Explorys, IBM, a national database including over 73 million patients. Patients were divided based on age (18-64 and ≥ 65 years; for female cancers 18-49 and ≥ 50 years), race (Caucasians and AA), and BMI (18.5 - &lt; 25 and ≥ 25.0 kg/m 2 ). The odds ratio (OR) and 95% confidence interval (CI) for multiple cancer rates in AA compared to Caucasians were calculated with P values &lt;0.001 considered significant. Results: N: Normal BMI EW: Excess weight (Females) C: Caucasian S: Significant NS: Non-significant. Conclusions: Our results show a significantly lower than expected prevalence of screenable cancers in AA compared to Caucasians, diverging widely from established incidence rates. The difference was more remarkable in pre-Medicare age (&lt; 65 years) and excess weight patients. These disparities are concerning for a compromised healthcare access contributing to underdiagnosis of cancer or shorter survival among AA in the US.[Table: see text]
Multifunctional magnesium incorporated scaffolds by 3D-Printing for comprehensive postsurgical management of osteosarcoma
Authors: Jing Long, Wei Zhang, Yingqi Chen, Bin Teng, Ben Liu, Huilin Li, Zhenyu Yao, Dou Wang, Long Li, Xue-Feng Yu, Ling Qin, Yuxiao Lai
Journal: Biomaterials (2021)
Retrospective analysis of multiparametric MRI to predict complete pathologic response after neo-adjuvant chemotherapy for muscle invasive bladder cancer.
Authors: Daan De Maeseneer, Pieter De Visschere, Mats Van den Broecke, Geert Villeirs, Sofie Verbeke, Karel Decaestecker, Sylvie Rottey
Journal: Journal of Clinical Oncology (2021)

e16535 Background: Muscle invasive bladder cancer (MIBC) is a life-threatening disease. Treatment is multimodal combining neo-adjuvant cisplatin-based chemotherapy (NAC) and radical cystectomy (RC). Accurately predicting complete pathologic response (pCR) using multiparametric MRI (mpMRI) could impact peri-operatively treatment. Methods: MIBC patients receiving NAC were evaluated at our institution with mpMRI before, after 2 cycles and after 4 cycles of dose dense MVAC (ddMVAC). Response after 4 cycles was retrospectively assessed using the method earlier described by Necchi et al with blinding of the readers for the pathological result of RC. Two radiologists independently evaluated 3 questions: residual disease at T1/T2-weighted images, presence of spots of restrictive diffusion within the bladder wall on diffusion-weighted imaging, and presence of focal contrast enhancement in the bladder wall on dynamic contrast enhanced images. Radiographic complete response (rCR) was defined as “No” on all three questions. Results: A total of 46 patients were identified having received ddMVAC for urothelial MIBC. Six patients did not undergo RC after NAC and were excluded from this analysis. Eleven out of 40 (28%) patients showed a complete pathologic response (ypT0). Baseline characteristics were similar compared to non-complete pathologic responders ( &gt; ypT0), with the exception of hydronephrosis (9% in ypT0 vs. 52% in &gt; ypT0). mpMRI questions could be assessed in 37 of 40 patients (93%). rCR was seen in 5 patients and was significantly associated with pCR (1-sided p value 0.021). Although sensitivity was low (36%), specificity was very high (96%) of this 3-step assessment. Positive likelihood ratio was 9.45, negative likelihood ratio 0.66. Concordance of assessment was very high. Conclusions: Using the 3-step imaging approach of Necchi et al, mpMRI can predict pCR after neo-adjuvant cisplatin-based chemotherapy with high specificity but low sensitivity. mpMRI should be included in future trials of multimodal management of MIBC and is an important predictive asset in routine clinical management.[Table: see text]
Development of β-globin gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell disease
Authors: Annalisa Lattanzi, Joab Camarena, Premanjali Lahiri, Helen Segal, Waracharee Srifa, Christopher A. Vakulskas, Richard L. Frock, Josefin Kenrick, Ciaran Lee, Narae Talbott, Jason Skowronski, M. Kyle Cromer, Carsten T. Charlesworth, Rasmus O. Bak, Sruthi Mantri, Gang Bao, David DiGiusto, John Tisdale, J. Fraser Wright, Neehar Bhatia, Maria Grazia Roncarolo, Daniel P. Dever, Matthew H. Porteus
Journal: Science Translational Medicine (2021)

Preclinical efficacy and safety data in mice provide support for ex vivo β-globin gene correction to treat patients with sickle cell disease.
Real-world treatment patterns among advanced HR+/HER2- breast cancer patients in the post-CDK4/6 inhibitor era: An analysis of administrative claims data.
Authors: Tirza Areli Calderón Boyle, Soham Shukla, Lindsey Powers Happ, Shan Zheng, Boris Gorsh
Journal: Journal of Clinical Oncology (2021)

e18695 Background: The treatment paradigm for advanced HR+/HER2- breast cancer has been rapidly evolving since the approval of the first CDK4/6 inhibitor in the U.S. in 2015. Available literature on real-world utilization of various treatment options available to these patients remains limited. The objective of this study was to describe how advanced HR+/HER2- breast cancer treatment patterns have changed over time since the approval of novel CDK4/6 inhibitors. Methods: IBM MarketScan Research Databases, a nationally representative source of U.S. insurance claims data, was used to identify women diagnosed with advanced breast cancer between January 2015 and December 2019 via ICD-9/10 codes. Algorithms were applied to capture patients with HR+/HER2- subtype and advanced disease diagnosis. Patients were indexed on their advanced breast cancer diagnosis date and were required to have six months continuous enrollment in the insurance claims database prior to and after the index date to ensure patients included in the cohort were alive and contributed at least 12 months of data for analysis. Lines of therapy (LOTs) were constructed and treatment patterns were reported over time. Descriptive analyses were conducted using Instant Health Data software. Results: A total of 4,128 women (mean age: 58 years, IQR: 50-64 years) had received at least one systemic breast cancer treatment and were included in the analysis. During a mean follow-up time of two years, nearly 29% of patients received at least four LOTs for advanced disease. A high number of unique regimens were reported in each LOT (30 in 1L, 48 in 2L, 53 in 3L and 50 in 4L+). The distribution of the top 1L regimens changed significantly over time (Table). CDK4/6 inhibitor use in the 2L setting also increased substantially from 43% in 2015 to 68% in early 2019, while chemotherapy and endocrine monotherapy utilization decreased. Conclusions: These data reflect a significant shift in the treatment landscape for HR+/HER2- advanced breast cancer patients in real-world practice since the availability of CDK4/6 inhibitors. However, there remains significant heterogeneity in the use of other treatments in these patients and in treatment sequencing, suggesting potential unmet need with current therapies. Further insight into patient, clinical and community-level factors guiding treatment decisions in the real world is needed. [Table: see text]
Vaccinating children against SARS-CoV-2: maximise uptake among adults while prioritising the most vulnerable
Authors: Elia Abi-Jaoude
Journal: BMJ (2021)

Lavine and colleagues call for a much needed reconsideration of the push to vaccinate children against SARS-CoV-2.1 In my (highly privileged) social circle in Toronto, most 12 year olds have already had their first vaccine. Meanwhile, the number of fully vaccinated Canadian adults, including those at risk, remains low. To spell out the concerns with vaccinating children against SARS-CoV-2:
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: Yoon-La Choi, Sehhoon Park, Sergio Pereira, Seonwook Park, Minuk Ma, Jiwon Shin, Jisoo Shin, Kyunghyun Paeng, Donggeun Yoo, Chan-Young Ock, Se-Hoon Lee
Journal: Journal of Clinical Oncology (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 10 9 micrometer 2 area of CE or CS, and 5.9 x 10 6 TILs from 3,166 H&amp;E Whole-Slide Image (WSI) of multiple cancer types, annotated by board-certified pathologists. H&amp;E WSIs were divided into 1 mm 2 -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&amp;E image.
Changes in T lymphocyte subsets in different tumors before and after radiotherapy: A meta-analysis.
Authors: Xiaoxia Zhu, Qin Wang, Shangbiao Li, Simiao Qiao, Zhihao Zheng, Xiaotong Duan
Journal: Journal of Clinical Oncology (2021)

2525 Background: Radiation therapy (RT) induces an immune response, but the relationship of this response with tumor type is not fully understood. Methods: We searched English-language electronic databases including PubMed, EMBASE, and the Cochrane Library to collect studies about the changes in CD3+ T lymphocytes, CD4+ T lymphocytes, and CD8+ T lymphocytes before and after radiotherapy in tumor patients from January 2015 to December 2019. The quality of the included literature was evaluated using the NOS scale provided by the Cochrane Collaboration, and statistical software RevMan 5.4 was used to analyze the included literature. p &lt; 0.05 was considered to indicate statistical significance. Results: A total of 17 studies in 15 articles involving 1735 tumor patients were included. All data were collected within 1 month before or after radiotherapy. Meta-analysis showed that numbers of CD3 + T lymphocytes were significantly reduced after radiotherapy compared with before treatment (standard mean difference [SMD]: -0.76; 95% CI [-1.46, -0.06]; p = 0.03), as were those of CD4 + T lymphocytes (SMD: -0.50; 95% CI: [-0.88, -0.12]; p = 0.01), but there was no statistically significant difference for CD8+ T lymphocytes (SMD: 0.19; 95% CI: [-0.23, 0.62]; p = 0.38). Subgroup analysis showed significant decreases in CD3+ T lymphocytes in liver cancer,esophageal cancer, head and neck cancer, pancreatic cancer and breast cancer after radiotherapy. Numbers of CD4+T lymphocytes increased after radiotherapy in breast cancer,and a decrease was observed in liver cancer, esophageal cancer, colorectal cancer, and head and neck cancer. CD8+ T lymphocyte numbers also increased compared with before radiotherapy in esophageal cancer, lung cancer, and colorectal cancer. But a decrease in liver cancer and head and neck cancer. Conclusions: Numbers of CD3+ and CD4+ T lymphocytes decreased after radiotherapy, whereas CD8+ T lymphocytes showed no significant change. Within 1 month of radiotherapy, the tumor microenvironment showed an immunosuppressive state. The degree of immune response induced by radiotherapy differed between tumor types.