tbuckley/cabot-search huggingface dataset:
Income-inequality and rate of doctors per inhabitant and their influence on esophageal cancer mortality in Brazil.
Authors: Jean Henri Schoueri, Luis Eduardo Werneck De Carvalho, Isabella Batista Martins Portugal, Manuela de Almeida Roediger, Edige Felipe de Sousa Santos, Laercio da Silva Paiva, Luiz Carlos de Abreu, Fernando Luiz Affonso Fonseca, Vânia Barbosa do Nascimento, Fernando Adami
Journal: Journal of Clinical Oncology (2021)

e16089 Background: There are substantial disparities in esophageal cancer mortality across different social groups, including sex, race/ethnicity, geographical location and socio-economic status. Methods: This is an ecological study with secondary data from 2016 to 2018 that evaluated the effects of income-inequality and number of doctors per inhabitant on esophageal cancer mortality in Brazil and its Federative Units. The amount of deaths and the overall number of doctors were obtained from the Department of Informatics of the Unified Health System. Mortality was estimated per 100,000 individuals and age-standardized through the World Health Organization’s population, whereas the rate of doctor per inhabitant was calculated per 1,000 inhabitants. Income-Inequality was measured by the Gini index, obtained from the United Nations Development Programme. Linear regression was performed by the stepwise backward method. Results: Sex, Gini index values and oncology surgeons were all related to lower mortality rates (p &lt; 0.05), whereas clinical oncologists and general surgeons were both associated with higher mortality (p &lt; 0.05). Conclusions: Esophageal cancer mortality rates were influenced by both the type and amount of doctors per inhabitant of any given administrative region in Brazil, however there was no association found with regards to income inequality.[Table: see text]
Patterns of lung cancer in people living with human immunodeficiency virus (HIV): A retrospective, single-center study in Washington, D.C.
Authors: Margaret Pruitt, Rajesh Naidu Janapala, Faysal Haroun
Journal: Journal of Clinical Oncology (2021)

e21154 Background: Lung cancer is the leading cause of cancer death and the most common non-acquired immune deficiency syndrome defining malignancy in people living with HIV (PLWH). Disparities in outcomes have been observed despite lung cancer mortality reportedly decreasing in the general population over the last decade due to lower rates of smoking and the advent of novel therapies. To better understand the current trend in lung cancer in PLWH, we explored demographic characteristics, comorbidities, and lung cancer pathology and molecular data in this population. Methods: A retrospective search of patient charts was conducted from 2004 to January 2021 using billing codes for HIV and primary lung cancer. Patients who had incorrect HIV or primary lung cancer diagnoses were excluded. Results: The search yielded 45 patients, of which 11 were excluded as described above: 66% were males, 82% African American, and 18% Caucasian. About two-thirds of patients were living in zip codes with predominantly low to medium household incomes. The median pack years of patients diagnosed with Stage I or II non-small cell lung cancer (NSCLC) was 40, Stage III or IV NSCLC was 20, early stage small cell lung cancer (SCLC) was 30, and late stage SCLC was 60. The median time between HIV and lung cancer diagnoses was 21.7 years for Stage I or II NSCLC, 17.1 years for Stage III or IV NSCLC, 15.2 for early stage SCLC, and 13.3 for late stage SCLC. Of 26 patients with viral load (VL) data, 21 (80.7%) had VL less than 500 when lung cancer was diagnosed. Of the 33 charts with available pathology data, there were 16 adenocarcinomas, 6 squamous carcinomas, 3 adenosquamous carcinomas, 1 large cell neuroendocrine cancer, 4 SCLCs, 1 mesothelioma, and 2 unspecified NSCLCs. Of 19 patients with a histologic grade, 11 had a high-grade tumor (57.9%). For the NSCLCs, 8 were Stage I (28.5%), 2 Stage II (7.1%), 8 Stage III (28.5%), 9 Stage IV (32.1%), and 1 with an unspecified stage. One SCLC was early stage and the remaining 3 were late stage. Five patients had brain metastasis. Molecular data or PDL-1 expression was available for 10 adenocarcinomas (62.5%), 1 adenosquamous (33%), 3 squamous carcinomas (50%), and the large cell neuroendocrine cancer. An EGFR mutation was detected in 2 cancers. ALK rearrangement was found in 1. Other mutations were detected. Two cancers were in each PDL1 expression category: &lt; 1%, 1-50%, and &gt; 50%. Conclusions: Our study suggests that PLWH with lung cancer continue to have high rates of smoking. Viral load was well controlled. A range in stages of lung cancer was observed including earlier stages. Although molecular data was limited, available EGFR and ALK gene alterations, and PD-L1 expression prevalence were on par with that of the general population. With advancements in lung cancer treatment, additional research is needed in the PLWH population to better understand and mitigate disparities.
Safety and Efficacy of Thiotepa Based Conditioning Regimen in Patients Undergoing Allogeneic Stem Cell Transplantation: A Retrospective Single Center Experience
Authors: Jean Elcheikh, Radwan Massoud, Nour Moukalled, Basel Haffar, Ammar Zaherddine, Charafeddine Maya, Rami Mahfouz, Ali Bazarbachi
Journal: Blood (2017)
血液透析(HD)患者における、リポタンパクリパーゼ(LPL)活性の増加を伴う、脂質異常を改善するトリアセチルセルロース(CTA)透析
Authors: Otsubo Y, Tabe T, Masuda T, Toyama M, Yamaguchi H, Uruta Y, Uchida Y, Yamashita W, Arima T
Journal: Journal of the American Society of Nephrology (1994)
Multimodal circulating tumor DNA (ctDNA) colorectal neoplasia detection assay for asymptomatic and early-stage colorectal cancer (CRC).
Authors: Jeeyun Lee, Hee C Kim, Seung Tae Kim, Yupeng He, Paul Sample, Yoshiaki Nakamura, Victoria M. Raymond, Ariel Jaimovich, AmirAli Talasaz
Journal: Journal of Clinical Oncology (2021)

3536 Background: To improve average risk CRC screening compliance, additional options are needed, especially options that address patient and provider reported barriers such as time and convenience. LUNAR-2 is a multimodal blood-based colorectal neoplasia detection assay incorporating ctDNA assessment of somatic mutations and tumor derived methylation and fragmentomic patterns, aimed to maximize sensitivity for early stage CRC detection. We evaluated this test in a large patient cohort with newly diagnosed CRC. Methods: Individuals diagnosed with CRC between 2013-2016 consented to provide blood samples prior to surgical resection. Those treated with neoadjuvant chemotherapy were excluded. Isolated plasma samples (median 3mL from EDTA) from 434 individuals were analyzed with LUNAR-2 (Guardant Health, USA) and included in the analysis. Median age at CRC diagnosis was 63 years (range 28 - 89) and 41% were female. Control samples were from 271 age-matched cancer free individuals. “ctDNA detected” and “ctDNA not detected” results were generated by a model trained on a separate sample set (N=614) from both cancer free individuals and those with CRC. Calling threshold was determined based on this held-out set to target 90% specificity. ctDNA results and clinical characteristics were correlated. Results: Overall CRC sensitivity was 91% (393/434), with high sensitivity across all stages; 88% Stage I/II, 93% Stage III (Table). Specificity was 94% (255/271). There was no difference in sensitivity when excluding those with early (&lt;45 years) or late (&gt;84 years) onset CRC (90% sensitivity; 388/429; p=0.95; 88% Stage I/II, 93% Stage III). There were no differences in sensitivity for asymptomatic CRC (88%) compared to symptomatic CRC (91%; p=0.4; Table). However, higher cell-free DNA tumor fractions were observed in the symptomatic cohort. Sensitivity for detection of right-sided and left-sided CRC was similar (93% vs. 90%; p=0.5; Table). Conclusions: In this large early-stage CRC cohort, multimodal ctDNA assessment has high sensitivity for CRC detection with high specificity. Equivalent sensitivity in the asymptomatic cohort suggests this test will have clinically meaningful performance in an average risk screening population. A prospective registrational study is ongoing to evaluate the test in an average risk CRC screening cohort.[Table: see text]
Anlotinib in radioiodine-refractory differentiated thyroid carcinoma: A subanalysis based on ALTER01032 study for patients with poor baseline characteristics.
Authors: Yihebali Chi, Ming Gao, Yuan Zhang, Feng Shi, Ying Cheng, Zhuming Guo, Minghua Ge, Jianwu Qin, Jiewu Zhang, Zhendong Li, Xiaohong Zhou, Rui Huang, Xiaohong Chen, Hui Liu, Ruochuan Cheng, Zhengang Xu, Xiangqian Zheng, Dapeng Li, Pingzhang Tang
Journal: Journal of Clinical Oncology (2021)

6022 Background: Anlotinib (anlo), a multikinase inhibitor, has demonstrated a significant survival benefit in treating locally advanced or metastatic radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC) with a nearly 4 folds prolongation in median progression-free survival (mPFS) (HR = 0.21, p &lt; 0.0001) compared with placebo in a randomized, placebo-controlled phase 2 study (ALTER01032, NCT02586337). Older age, bone metastasis, structural progression within a short time are generally indicated as negative prognostic factors for thyroid cancer. This subanalysis explored the outcomes of patients (pts) enrolled in ALTER01032 study with these poor baseline characteristics. Methods: 113 pts were enrolled, 76 in anlo arm and 37 in placbo arm. The primary endpoint is PFS. Pts with older age (≥ 55), bone metastasis or radiographic documented disease progression within 3 months (mo) before enrollment were selected. The PFS and overall survival (OS) for these pts were estimated and compared. Since 64.9% pts in placebo arm received crossover treatment with open label anlo after progression while only 3 pts in anlo arm received post-study treatment, the penitential bias for OS from imbalance of subsequent treatment was adjusted by a two-stage estimation method. Results: The results of subanalysis were summarized in the table below. Pts with poor baseline characteristics showed higher risk of progression and death. Significant PFS prolongation was shown across all subgroups in pts received anlo compared with their counterparts who received placebo ( P &lt; 0.05). In pts with bone metastasis or structural progression within 3 mo, anlo treatment achieved significant OS benefit ( P &lt; 0.05). Also, in older pts, a trend of OS improvement was observed (HR = 0.85 (95% CI 0.37, 1.97)). Most pts in placebo arm received crossover anlo. After adjustment, a near-significant decrease of death risk was observed in older pts received anlo compared with those received placebo (HR = 0.48 (95% CI 0.20, 1.13)). Conclusions: This subanalysis showed anlo effectively improved both PFS and OS of pts with RAIR-DTC who have poor baseline characteristics above. Interestingly, although most pts in placebo arm received crossover anlo, they still have higher risk of death, indicating the importance of earlier treatment for these pts. Clinical trial information: NCT02586337. [Table: see text]
Urine Cultures at the Onset of Febrile Neutropenia (FN) in Patients with Haematological Malignancies Rarely Impact Antibiotic Management in the Absence of Urinary Symptoms
Authors: Sam Grigg, Patrick Date, Eliza A Hawkes, Douglas Johnson, Zoe Loh, Ortis Estacio, Andrew P Grigg
Journal: Blood (2017)
<i>NTRK, RET, BRAF,</i> and <i>ALK</i> fusions in thyroid fine-needle aspirates (FNAs).
Authors: Lori J. Wirth, Mimi I-Nan Hu, Steven G. Waguespack, Chrysoula Dosiou, Paul Ladenson, Masha J. Livhits, Peter M. Sadow, Jeffrey Krane, Brendan C. Stack, Mark Zafereo, Syed Z. Ali, Steven P Weitzman, Yangyang Hao, Joshua Babiarz, Giulia Kennedy, Richard Kloos
Journal: Journal of Clinical Oncology (2021)

6083 Background: Receptor tyrosine kinase (RTK) fusions may be targeted by small molecule inhibitors to treat various advanced tumors, including thyroid cancer. Clinical trials have studied selective inhibitors of ALK, BRAF, NTRK and RET, leading to several FDA-approved therapies. The Afirma Genomic Sequencing Classifier (GSC) classifies cytologically indeterminate thyroid nodules as molecularly benign or suspicious. The Xpression Atlas reports 905 genomic variants and 235 fusion pairs on GSC Suspicious, Suspicious for Malignancy (SFM), and Malignant FNA samples at the time of diagnosis. Here we report the prevalence of these fusion genes in real-world clinical practice. Methods: We analyzed anonymized data from 50,644 consecutive Bethesda III-VI nodule FNA samples submitted to the Veracyte CLIA laboratory for molecular testing using whole transcriptome RNA sequencing (RNA-Seq). Gene pairs are listed alphabetically. Results: 32,080 Bethesda III/IV nodules were classified as GSC Benign and 278 were Parathyroid Classifier positive. No ALK, BRAF, NTRK1/3, or RET fusions were identified among these samples. Among 16,594 Bethesda III/IV GSC Suspicious FNAs, 3% (n = 529) were positive for ALK, BRAF, NTRK1/3 or RET fusions. Among the 1,692 Bethesda V/VI FNAs, the proportion of positive nodules was 8% (n = 135). Among these combined cohorts of Bethesda III/IV GSC Suspicious and Bethesda V/VI, the most common gene fusions observed for each of the 5 studied RTK genes was: ETV6/NTRK3 (n = 164, 72% of NTRK3 fusions), CCDC6/RET (n = 104, 55% of RET), BRAF/SND1 (n = 32, 20% of BRAF), ALK/STRN (n = 20, 37% of ALK), and NTRK1/TPM3 (n = 14, 50% of NTRK1). BRAF showed the highest diversity of fusions, with 80 gene partners. Different gene partners with RET, ALK, NTRK1, and NTRK3 numbered 25, 11, 9, and 5 , respectively . Conclusions: Whole-transcriptome RNA-seq on small sample thyroid FNA specimens can identify clinically relevant ALK, BRAF, NTRK, and RET fusions across Bethesda categories. The prevalence ranges from 3% in Bethesda III/IV Afirma GSC Suspicious specimens to 8% among Bethesda V/VI specimens. Future studies need to determine if detection of precision medicine candidates by pre-operative FNA can optimize initial treatment, predict response to treatment, and prioritize selective targeted therapy should systemic treatment be needed.[Table: see text]
The SARS-CoV-2 B.1.351 lineage (VOC β) is outgrowing the B.1.1.7 lineage (VOC α) in some French regions in April 2021
Authors: Bénédicte Roquebert, Sabine Trombert-Paolantoni, Stéphanie Haim-Boukobza, Emmanuel Lecorche, Laura Verdurme, Vincent Foulongne, Mircea T. Sofonea, Samuel Alizon
Journal: Eurosurveillance (2021)

To assess SARS-CoV-2 variants spread, we analysed 36,590 variant-specific reverse-transcription-PCR tests performed on samples from 12 April–7 May 2021 in France. In this period, contrarily to January–March 2021, variants of concern (VOC) β (B.1.351 lineage) and/or γ (P.1 lineage) had a significant transmission advantage over VOC α (B.1.1.7 lineage) in Île-de-France (15.8%; 95% confidence interval (CI): 15.5–16.2) and Hauts-de-France (17.3%; 95% CI: 15.9–18.7) regions. This is consistent with VOC β’s immune evasion abilities and high proportions of prior-SARS-CoV-2-infected persons in these regions.
Treatment changes in prostate cancer patients on active treatment during the COVID-19 pandemic in a community cancer center in New York City.
Authors: Rose Snyder, Trishala Meghal, Andrew Wood, Ariel Schulman, Kevin Douglas Becker, Yiwu Huang, Jay Steven Lipshitz, Lan Mo, Yiqing Xu
Journal: Journal of Clinical Oncology (2021)

e18750 Background: The surge of the SARS coronavirus-2 (COVID-19) pandemic posed great challenges in the oncology community for optimal management of cancer patients. We sought to analyze the treatment changes experienced by the prostate cancer patients in March, April and May 2020 and to compare these treatment decisions to the published guidelines. Methods: We focused on patients currently receiving androgen deprivation therapy (ADT) with leuprolide acetate, and/or oral anti-androgen agents (Androgen receptor axis targeted agent, ARAT), or chemotherapy. Electronic medical records were reviewed, and the oncologists and nurse practitioners were interviewed to understand the decision-making process. Results: Seventy-five patients were included, median age 72 years old (range 47-95). All were taking ADT, and 21 were also taking ARAT, and 3 were also receiving chemotherapy. The incidence and indications for their ADT treatments and schedule changes are shown in the table below. Twenty-seven patients (36%) experienced delays in their ADT treatment, and the percentage of treatment change was similar in categories of metastatic hormone sensitive prostate cancer (mHSPC), metastatic castration resistant cancer (mCRPC), biochemical recurrence as well as stage IVA post surgery. Four patients were receiving neoadjuvant ADT planned prior to definitive radiation, and none had schedule change. One patient with mHSPC and 2 patients with mCRPC continued chemotherapy as planned. One patient declined recommended chemotherapy for mCRPC. Two patients were given q 3 months dose of ADT instead of q 1m, while all the rest were already receiving q3 months dosing. Among the 27 patients who had schedule change, 12 (44.4%) patients had a discussion with their providers first, and 15 patients (55.6%) did not keep their treatment appointment. Conclusions: About one third of patients changed ADT injection schedule with a similar percentage in patients with mHSPC, or mCRPC or Biochemical recurrence, or IVA after surgery. Every 3 months dosing of ADT recommended by NCCN significantly decreases exposure to COVID -19, delaying or skipping treatment was still encountered due to health concern or travel limitations. On the other hand, all patients receiving neoadjuvant ADT, or chemotherapy stayed on schedule. Although NCCN guideline recommended delaying myelosuppressive therapy, palliative chemotherapy for symptomatic, refractory patients may still be a priority.[Table: see text]
Noninvasive detection of chromosomal instability in plasma circulating cell-free DNA for early pan-cancer diagnosis using low-pass whole-genome sequencing.
Authors: Ran Lv, Fang Lv, Pei Zhihua, Jianing Yu, Xiuyu Zhao, Yiqian Liu, Yaxi Zhang, Geng Chen, Weizhi Chen, Ji He
Journal: Journal of Clinical Oncology (2021)

e22509 Background: Genomic instability is a typical characteristic of the majority of cancers. Early non-invasive detection of cancer is the most effective way of improving the success of treatment and prognosis at present. Traditional tumor screening methods have limitations in terms of selection methods, sensitivity, specificity, cost, and comfortability. Furthermore, although traditional tumor screening is useful for common cancers, there is no available screening test for rare cancers. Here we developed a novel method for cancer detection with Low-Pass Whole Genome Sequencing (WGS) of cell-free DNA (cfDNA). Methods: The cfDNA samples from 52 healthy donors were first used to establish a blacklist of bins. Then the baseline was established to calculate the chromosomal instability score (CINscore). We optimized the parameters of our model using the following discovery datasets: healthy controls (n = 50), breast invasive carcinoma (BRCA) (n = 44), ovarian serous cystadenocarcinoma (OV) (n = 25), colon adenocarcinoma/rectum adenocarcinoma esophageal carcinoma (COREAD) (n = 52), hepatocellular carcinoma (HCC) (n = 43), Gastric adenocarcinoma (GAC) (n = 31); pancreatic adenocarcinoma (PAC) (n = 38), non-small cell lung cancer (NSCLC) (n = 45). Results: We further evaluated the performance of our method using the confirmation datasets of healthy controls (n = 30), BRCA (n = 20), prostate adenocarcinoma (PRAD) (n = 6), OV (n = 7), head and Neck squamous cell carcinoma (HNSC) (n = 10), Uterine Corpus Endometrial Carcinoma (UCEC) (n = 6), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) (n = 5), COREAD (n = 75), HCC (n = 50), GAC (n = 31), cholangiocarcinoma (CHOL) (n = 8), PAC (n = 10), NSCLC (n = 98), esophageal carcinoma (ESCA) (n = 10), and nasopharyngeal carcinoma (NAC) (n = 4). Overall, the area under the curve (AUC) for pan-cancer is 88.7%, and for BRCA, COREAD, HCC, NSCLC, and GAC are 91.7%, 90.0%, 94.5%, 83.4%, and 88.6%, respectively. Moreover, our approach achieved good performance on the the early stage samples of pan-cancer (AUC = 84.3%) as well as COREAD (AUC = 89.3%) and NSCLC (AUC = 79.0%). Conclusions: Collectively, we show that the CINscore inferred from low-pass WGS could be applied in early non-invasive detection of different cancers with high accuracy. Our approach may aid the improvement of the cancer diagnosis.
The efficacy and safety of anlotinib in refractory/recurrent/advanced pediatric solid tumors: A retrospective study.
Authors: Suying Lu, Ye Hong, Huimou Chen, Liuhong Wu, Jia Zhu, Juan Wang, Feifei Sun, Zijun Zhen, Yi Que, Lian Zhang, Xiaofei Sun, Junting Huang, Yizhuo Zhang
Journal: Journal of Clinical Oncology (2021)

11556 Background: Refractory and recurrent advanced pediatric solid tumors are short of effective treatment and with a dismal outcome, thus an urgent need for novel and effective treatment. The aim of the study is to evaluate the efficacy and safety of anlotinib, a novel and oral multi-target receptor tyrosine kinase inhibitor, in refractory or recurrent advanced pediatric solid tumors. Methods: The retrospective, single-institutional, observed study was conducted in Sun Yat-sen University cancer center in China. Refractory, recurrent, or advanced pediatric solid tumors patients treated with anlotinib between 2018 to 2020 were evaluated. Results: Forty-one patients and thirty patients were enrolled in the study to evaluated efficacy and safety, respectively. The objective response ratio (ORR) was 12.2% (95%CI 1.7-22.7): complete response (n = 0) and partial response (n = 5) (Table). The disease control rate (DCR) was 65.9% (95%CI 50.7-81). The median progression-free survival (PFS) was 2.87 months (95%CI 0.86-4.88). According to anlotinib treatment schedule, all patients were divided into three groups: anlotinib monotherapy (A, n = 16), anlotinib combined with immune checkpoint inhibitor treatment (A + ICI, n = 6), anlotinib combined with salvage chemotherapy (A + SC, n = 19). The ORR, DCR and median PFS for three groups were 6.3% (95%CI 7.1-19.6), 56.3% (95%CI 28.9-83.6), 2.43months, 16.7% (95%CI 26.2-59.5), 66.7% (95%CI 12.5-120.9), 1.13months, 15.8% (95%CI 2.3-33.8), 73.7% (95%CI 51.9-95.5), 2.87months, respectively. There was no significantly difference between three groups in aforementioned response index. The incidence rates of any grade and grade 3-4 adverse events were 80% and 20%, respectively. Bleeding (20%), hand-foot syndrome (13.3%), and diarrhea (13.3%) were the most common adverse events. Grade 3-4 adverse events include hypertension, hand-foot syndrome, diarrhea, anemia, and thrombocytopenia. There was no adverse events-related death. Conclusions: For heavily pretreated pediatric solid tumors, anlotinib may be an effective treatment with tolerable adverse events. Further prospective randomized controlled clinical study is warranted.[Table: see text]