tbuckley/cabot-search huggingface dataset:
Efficacy and safety of mFOLFIRINOX in patients with borderline resectable and locally advanced unresectable pancreatic cancer: Intention-to-treat population analysis.
Authors: Inhwan Hwang, Changhoon Yoo, Kyu-Pyo Kim, Jae Ho Byun, Jae Ho Jeong, Heung-Moon Chang, Baek-Yeol Ryoo
Journal: Journal of Clinical Oncology (2020)

720 Background: Borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAUPC) are heterogeneous disease entity with various prognosis. Based on the phase III PRODIGE trial, (m)FOLFIRINOX has been widely used for the management of patients with BRPC and LAUPC. Considering the lack of large phase 3 trial of (m)FOLFIRINOX for BRPC and LAUPC, real-life evidences of (m)FOLFIRINOX are needed. Methods: In this retrospective analysis, 199 patients who received at least one dose of (m)FOLFIRINOX between February 2013 and January 2017 were included. Endpoints of this study were objective response rates (ORR), surgical resection rate, progression-free survival (PFS) and overall survival (OS). Results: Median age was 60 years (range, 33-79) and 62.3% of patients were male. Pancreas head (n=112, 56.3%) was the most common primary tumor site, followed by body (n=42, 21.1%) and multifocal (n=34, 17.1%). By an independent radiology review, patients were classified to BRPC (n=75, 37.7%) and LAUPC (n=124, 62.3%). With median 40.3 months (95% CI, 36.7-43.8) of follow-up duration in surviving patients, ORR was 26.6% (n=53), median PFS and OS were 10.6 months (95% CI, 9.5-11.7) and 17.1 months (95% CI, 13.2-20.9), respectively. There was no difference in PFS and OS between BRPC and LAUPC (median PFS, 11.1 months [95% CI, 8.8-13.5] vs. 10.1 months [95% CI, 8.4-11.8], p=0.47); (median OS, 18.4 months [95% CI, 16.1-20.8] vs. 17.1 months [95% CI, 13.2-20.9], p=0.50). Curative-intent surgery (R0 and R1) was done in 63 patients (33.2%, 49 for R0 and 14 for R1) after treatment with (m)FOLFIRINOX. Resection rates were 58.2% in BRPC patients and 19.4% in LAUPC patients (p&lt;0.001). In patients who underwent curative-intent surgery, median disease-free survival since surgery was 10.4 months (95% CI, 8.3-12.5 ) and there was no difference according to the baseline disease extent (BRPC vs. LAUPC): 10.0 months (95% CI, 7.5-12.5) vs. 12.0 months (95% CI, 3.7-20.3), p=0.37. Conclusions: (m)FOLFIRINOX is effective therapy for BRPC and LAUPC patients. Significant proportion of patients could receive curative-intent surgery.
A well defect-suitable and high-strength biomimetic squid type II gelatin hydrogel promoted in situ costal cartilage regeneration via dynamic immunomodulation and direct induction manners
Authors: Meilu Dai, Baiyan Sui, Yujie Hua, Yiqing Zhang, Bingkun Bao, Qiuning Lin, Xin Liu, Linyong Zhu, Jiao Sun
Journal: Biomaterials (2020)
A new type of microscopy to help scientists examine skin cancers
Authors: J. Pérez‐Anker, S. Ribero, O. Yélamos, A. García‐Herrara, L. Alos, B. Alejo, M. Combalia, D. Moreno‐Ramírez, J. Malvehy, S. Puig
Journal: British Journal of Dermatology (2020)

Ex vivo (meaning that it takes place outside the body) confocal microscopy is an imaging technique which allows scientists to look at samples of skin that have been removed by biopsy (where a small tissue sample is removed surgically), and it is often used to diagnose skin cancers including basal cell carcinomas (BCC). There are two main types, fluorescence confocal microscopy (FCM) and reflectance confocal microscopy (RCM), allowing the visualization of different structures in the tissue sample. FCM requires a stain, a type of dye, to be added to the sample and has been used for the analysis of BCC during a type of surgery called Mohs micrographic surgery (MMS). MMS involves removing a thin layer of the tumour at a time with a very small margin of healthy skin around it, and each layer is immediately checked under the microscope. In RCM, a beam of light is focused on a small area of skin. Varying amounts of this light are reflected back depending on the structure of the cells. This creates a grey‐scale image of a section of the skin which allows doctors to see abnormalities. Recently, a new, faster ex vivo confocal microscope has been developed which uses reflectance and fluorescence simultaneously, providing high‐resolution images in both modes separately and in combination (fusion mode). In this study, the researchers, from Spain, explain which features of a BCC are seen using each of the methods, and if one of the methods is better than the others. They also wanted to develop a new staining protocol to improve the visualization of BCC under the different modes. The researchers used BCCs which were excised (removed) using Mohs surgery in their department. The specimens were first stained with acridine orange and then stained using both acetic acid and acridine orange. Most features were better visualized with the fusion mode using double staining. They also identified new ex vivo confocal microscopy features, dendritic and plump cells, which have not been previously reported. Their results suggest that some features (nuclei characteristics) are better visualized in FCM but others (cytoplasm and surrounding stroma) are better visualized in RCM. For this reason, using both reflectance and fluorescence at the same time, using fusion mode, seems to be beneficial. This summary relates to the study: Basal cell carcinoma characterization using fusion ex vivo confocal microscopy: a promising change in conventional skin histopathology
Tumor inflammatory signature as a biomarker of response to immunotherapy in lung cancer.
Authors: Sarabjot Pabla, Erik Van Roey, Jeffrey M. Conroy, Sean Glenn, Yirong Wang, Mary Nesline, Blake Burgher, Vincent Giamo, Jonathan Andreas, Felicia L. Lenzo, Carl Morrison
Journal: Journal of Clinical Oncology (2020)

47 Background: Tumor Inflammation signatures (TIS) comprising multiple immune genes have been shown to enrich for response to ICI. To study this immune phenotype in a large cohort of clinically evaluated patients, we studied gene expression data for a stable pan-cancer tumor inflammation profile and clinical response to ICI. Methods: 1323 FFPE tumors from 35 histologies were tested by RNA-seq, PD-L1 IHC and DNA-seq for TMB. Unsupervised analysis of the RNA-seq data revealed a cluster of 160 genes which separated inflamed from non-inflamed tumor microenvironments (TME). A TIS, algorithmically defined as the mean mRNA expression of the 160 genes was developed with each tumor assigned into a weak, moderate or strong inflammation group. PD-L1 IHC was performed using DAKO 22C3 antibody and considered positive if TPS ≥1%. TMB &gt; 10 mut/Mb was considered high. The TIS, PD-L1 and TMB were independently applied to 110 NSCLC cases for association with ORR to ICIs by RECIST criterion. Results: Unsupervised clustering identified 3 inflammation clusters in the 1323 samples; inflamed (n = 439; 33.2%), borderline (n = 467; 35.3%) and non-inflamed (n = 417; 31.5%). 160 genes are over-represented by T &amp; B-cell activation, IFNg, chemokine, cytokine and interleukin pathways. The TIS algorithm results in an inflammatory score that leads to 3 distinct groups of strong (n = 384; 29.0%), moderate (n = 354; 26.8%) and weak (n = 585; 44.2%) inflammation. Strongly inflamed tumors are over-represented by PD-L1+ tumors (240/384) whereas weakly inflamed tumors are significantly under-represented by PD-L1+ tumors (369/585; p = 1.02e-14). Strongly inflamed tumors presented with improved ORR to ICI in NSCLC (36.6%; 16/44; p = 0.051). Similar results were observed for overall survival for strongly inflamed tumors (median = 16 months; p = 0.0012) vs. weakly inflamed tumors (median = 8 months). ORR for PD-L1+ 33.96% (p = 0.026) and TMB high 21.43% (p = 0.83) were observed. Conclusions: Concurrent measurement of multiple markers led to a comprehensive, stable TIS that predicts host immune response. A strongly inflamed TIS was associated with higher ORR versus single biomarker PD-L1 and TMB in NSCLC.
<i>Withdrawn:</i> 基因是否重要?先天性黑素细胞痣的基因型‐表型与基因型结果的相关性
Authors: S. Polubothu, N. McGuire, L. Al‐Olabi, W. Baird, N. Bulstrode, J. Chalker, D. Josifova, D. Lomas, J. O'Hara, J. Ong, D. Rampling, P. Stadnik, A. Thomas, E. Wedgeworth, N.J. Sebire, V.A. Kinsler
Journal: British Journal of Dermatology (2020)

DOI: 10.1111/bjd.19296 S. Polubothu N. McGuire L. Al‐Olabi et al. Does the gene matter? Genotype‐phenotype and genotype‐outcome associations in congenital melanocytic naevi. https://onlinelibrary.wiley.com/doi/10.1111/bjd.18747 https://onlinelibrary.wiley.com/doi/10.1111/bjd.18762 (Mandarin) The above Plain Language Summary from the British Journal of Dermatology, published online on 03 February 2020 in Wiley Online Library (wileyonlinelibrary.com), and in print and online in issue 182.2, also translated into Mandarin in issue 182.2, has been withdrawn by agreement between the authors, the journal's editor‐in‐chief, John Ingram, the British Association of Dermatologists, and John Wiley & Sons Limited. Both the original Plain Language Summary and the Mandarin translation of the Plain Language Summary have been withdrawn. The Plain Language Summary incorrectly attributed authorship to the authors of the original article S. Polubothu N. McGuire L. Al‐Olabi, et al. The Plain Language Summary was written by a BJD in‐house dermatologist and not the authors. The authors of the original article were inserted to establish a link to the paper, and not to attribute authorship of the Plain Language Summary. The Plain Language Summary has now been withdrawn and replaced with a version provided by the authors. We apologise for this error, and have since changed the way our Plain Language Summaries are written and attributed.
Impact of inaccurate clinical staging for gastric cancer on patient survival outcomes.
Authors: Michelle Ju, Matthew R. Porembka
Journal: Journal of Clinical Oncology (2020)

345 Background: Accurate clinical staging (CS) in gastric cancer is critical for appropriate treatment selection and prognostication, but CS remains highly ineffective. Our study aims to evaluate the factors associated with inaccurate CS, the impact of inaccurate CS on patient outcomes, and effect of adjuvant therapy in patients with inaccurate CS. Methods: We conducted a retrospective review of the NCDB of patients diagnosed with clinical early-stage gastric adenocarcinoma based on AJCC 8th edition (cT1-2, N0, M0) between 2004-2016. Those who did not undergo upfront surgery or had missing pathologic staging data were excluded. Patients were classified into 3 groups: accurately staged (AS) if pathologic staging confirmed early-stage cancer, inaccurately staged with receipt of adjuvant therapy (IS+), and inaccurately staged with no receipt of adjuvant therapy (IS-). Logistic regression using stepwise selection was utilized to assess the impact of factors on CS accuracy and receipt of adjuvant therapies. Kaplan-Meier and Cox Proportional Hazard methods were used to compare survival outcomes. Results: Approximately 39% of patients (2841/7199) were understaged. T2 tumors, non-well differentiated tumors, and diffuse type histology were associated with increased likelihood of inaccurate CS. Age &gt;60, female sex, Asian/Black race, and non-cardia tumor location were associated with decreased likelihood of inaccurate CS. Only 44% of patients who were inaccurately staged received adjuvant chemotherapy/radiation. Age &gt;75 and fundus/body tumor location were associated with decreased likelihood of receiving adjuvant therapies, while more advanced pT and pN stage were associated with increased likelihood. Treatment facility type (community vs. academic) had no impact on likelihood of accurate CS or receipt of adjuvant treatment after inaccurate CS. 5-year overall survival was significantly different between groups (71.7% AS, 48.3% IS+, 51.1% AS-; p&lt;0.001). Conclusions: CS is inadequate, and understaging has detrimental effects on patient survival outcomes. Novel strategies for improved CS are needed to improve patient care.
Interim results from a phase Ib/II study of pepinemab in combination with avelumab in advanced NSCLC patients following progression on prior systemic and/or anti-PDx therapies.
Authors: Michael Rahman Shafique, Terrence Lee Fisher, Elizabeth E. Evans, John E. Leonard, Desa Rae Electa Pastore, Crystal L. Mallow, Ernest Smith, Andreas Schröder, Kevin M. Chin, J. Thaddeus Beck, Megan Ann Baumgart, Ramaswamy Govindan, Nashat Y. Gabrail, Rachel E. Sanborn, Alexander I. Spira, Nagashree Seetharamu, Yanyan Lou, Aaron Scott Mansfield, Jonathan Wade Goldman, Maurice Zauderer
Journal: Journal of Clinical Oncology (2020)

75 Background: Despite progress of immune checkpoint therapies, many cases of non-small cell lung cancer (NSCLC) are refractory or acquire resistance to current therapies. Antibody blockade of semaphorin 4D (SEMA4D, CD100) can overcome resistance mechanisms of immune exclusion and myeloid suppression. Importantly, combinations of anti-SEMA4D with various immunotherapies enhanced T cell infiltration and activity, as well as durable tumor regression in preclinical models. Pepinemab (VX15/2503) is a first-in-class humanized monoclonal antibody targeting SEMA4D. Methods: The CLASSICAL-Lung clinical trial (NCT03268057) evaluates the combination of pepinemab with anti-PD-L1 antibody avelumab to couple beneficial modifications of the immune microenvironment via pepinemab with immune activation via checkpoint inhibition. This ongoing study evaluates the safety, tolerability and efficacy of the combination in patients with advanced (stage IIIB/IV) NSCLC, including immunotherapy-naïve (ION) patients and patients whose tumors progressed during or following immunotherapy (IOF). Results: The combination was well tolerated with no major safety signals identified. Among 29 evaluable IOF patients, two experienced confirmed partial response (PR) with 63% and 52% tumor reduction on study following acquired resistance to prior treatment with pembrolizumab, 15 additional patients experienced stable disease, and at least 5 patients with durable clinical benefit of ≥ 23 weeks. Among 21 evaluable ION patients, 5 experienced PR, clinical benefit ≥ 1 year was observed in 3 patients, and Disease Control Rate was 81%. Analysis of pre- and on-treatment biopsies demonstrated increased CD8+ T cell density correlating with response, reduction or elimination of tumor in 11/13 biopsies from subjects with PR or SD. Conclusions: Interim analysis suggests the combination of pepinemab plus avelumab is well tolerated and shows initial clinical signals of antitumor activity. Updated clinical response data (minimum of 6 mo. follow-up), as well as additional immunophenotyping of both inflammatory and suppressive myeloid cells will be presented. Clinical trial information: NCT03268057.
Inquiry slams system’s “wilful blindness” that allowed rogue surgeon to carry on practising
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The healthcare system was “dysfunctional at almost every level” when it came to keeping patients safe from the rogue breast surgeon Ian Paterson, an independent inquiry has concluded.1

In its final report, published on Tuesday 4 February, the inquiry, led by the retired bishop Graham James, delivered a damning verdict on how Paterson, a former consultant surgeon at Heart of England NHS Foundation Trust in Birmingham, was able to continue working for more than a decade in the NHS and private sector despite numerous concerns raised about his professional competence and conduct.

Paterson was jailed for 15 years in 2017 after being convicted of 17 counts of wounding with intent and three counts of wounding in his treatment of 10 patients at private hospitals run by Spire Healthcare.2 The Court of Appeal later …
Out-of-pocket spending (OOPS) and financial toxicity survey for neuroendocrine tumor (NET) patients.
Authors: Aman Chauhan, Rohitashva Agrawal, Rebecca Edwins, Maryann Wahmann, Bob Wahmann, Lauren Corum, Lowell Brian Anthony
Journal: Journal of Clinical Oncology (2020)

632 Background: Incidence and prevalence of neuroendocrine tumors (NETs) are on the rise. However, with the increasing burden of the disease, there is a need to understand financial toxicity associated with NET management. Especially the out of pocket spending or expenses made by patients and family members, which affects the management and treatment adherence. We report results of our prospective online survey based study looking into determinants and the burden of financial toxicity in NET patients. Methods: We collaborated with NCAN (Neuroendocrine Cancer Awareness Network) a national NET patient support group for our prospective online questionnaire-based survey. After IRB approval, NCAN disseminated online link to the survey on their webpage. The survey had twenty-one questions with the goal of at least 200 complete responses. Results: We received 215 responses before we decided to stop the survey for analysis. The average age of the respondents was 58.4 years. 75% of respondents were females with most repsondents of the survey (37%) being graduates. About 41% of respondents had small bowel NET while 27% had pancreas NET as their NET diagnosis. The median income of the respondents was $65000/year. Median oncology visits were reported to be 4 per year. Median co-pay for the NET specialist visit was found to be $30. The median spending on travel for the physician`s appointment was $250 per visit to see NET specialists. Median monthly insurance premium was $300. Study participants reported spending $75 out of pocket on NET related care every month on top of insurance premiums. More than half of the respondents were on Somatostatin analogues only as their main treatment. About 21% mentioned that they were not able to get required treatment due to cost related issues. Conclusions: The preliminary analysis of the survey gave us an insight into financial toxicity related to NET management. Although most NETs are indolent, the chronic nature of disease and associated, symptom management is often time and resource-intensive. Many patients mentioned having issues with the coverage of insurance and having to travel a long distance to see a NET specialist, which demonstrate a lack of access to NET specialists.
The world-wide incidence of biliary tract cancer (BTC).
Authors: Huifen Wang, Ping Sun, Katherine Baria
Journal: Journal of Clinical Oncology (2020)

585 Background: Existing epidemiologic research for BTC is limited to certain subtypes, eg gallbladder cancer (GBC), or combines BTC with liver cancer, and only reports regional statistics. Main sources for global BTC epidemiology (particularly anatomic sites) are literature reviews, which can be subject to limitations like inconsistent classification of subtypes, and varying standard population adjustment and comparison timeframes. Given the increasing incidence of BTC, it is critical to monitor global epidemiology to provide insight to public health management and clinical program development. Methods: We evaluated BTC incidence in 15 countries using the Cancer Incidence in Five Continents database Volume XI (CI5 XI) from the International Agency for Research on Cancer. Most CI5 XI registries cover data from 2008-12 with some variations. Incidence was examined by country, region, and anatomic site (extrahepatic cholangiocarcinoma, ECC; intrahepatic cholangiocarcinoma, ICC; GBC; ampulla of Vater cancer, AVC; and unspecified BTCs). Incidence was adjusted to standard world population and reported as age-standardized rate (ASR; per 100,000 person-years) with standard error (SE). Results: The highest incidence of total BTC was in South Korea (SK; ASR = 3.00, SE = 0.02) and lowest in the UK (ASR = 0.66, SE = 0.01). Overall, BTC incidence was higher in Asian countries than Western, and in Asian-Americans than the general US population (ASR = 1.00, SE = 0.02 and 0.77, SE &gt; 0.01, respectively). In Thailand, BTC incidence was higher in the North than South (ASR = 1.93, SE = 0.05 and 1.05, SE = 0.03, respectively). GBC and ECC are the top common subtypes in most countries reported. SK had the highest incidence of all subtypes, with ASR &gt; 2 in GBC, ECC, and ICC. Outside of SK, GBC and ECC were most common in Japan (ASR = 1.93, SE = 0.02 and 2.66, SE = 0.03, respectively); ICC was most common in Thailand (ASR = 1.73, SE = 0.05) and high in France (ASR = 1.01, SE = 0.03). Conclusions: These registry data support past reports of higher BTC incidence in Asian vs Western countries as well as regional variation within countries. Data also suggests that high BTC rates in Asian populations may not be entirely geographical as Asian-Americans suffer a higher BTC incidence than the overall US population.
リチウム-ピロカルピン誘発慢性側頭葉てんかんによるP糖蛋白質を過剰発現しているラットにおけるフェニトイン耐性を克服するPluronicP85被覆ポリ(シアノアクリル酸ブチル)ナノ粒子【Powered by NICT】 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Fang Ziyan, Chen Shuda, Qin Jiaming, Chen Bao, Ni Guanzhong, Chen Ziyi, Zhou Jueqian, Li Ze, Ning Yuping, Wu Chuanbin, Zhou Liemin
Journal: Biomaterials (2016)
Informing metastatic colorectal cancer patients by quantifying multiple scenarios for survival based on real-life data.
Authors: Patricia Hamers, Marloes A.G. Elferink, Rebecca K. Stellato, Cornelis J. A. Punt, Anne Maria May, Miriam Koopman, Geraldine R. Vink
Journal: Journal of Clinical Oncology (2020)

32 Background: Reported median overall survival (mOS) in trials of metastatic colorectal cancer (mCRC) patients receiving systemic therapy has increased to over 30 months. When informing patients, many clinicians quote the mOS reported in these trials. It is uncertain whether trial results translate to real-life populations. Moreover, patients prefer presentation of multiple survival scenarios over presentation of just mOS. Therefore, we quantified multiple scenarios for survival time of real-life mCRC patients. Methods: Nationwide population-based data of all stage IV CRC patients diagnosed between 2008 and 2016 were obtained from the Netherlands Cancer Registry. We calculated percentiles (scenarios) of OS per year of diagnosis for the total population, and for treatment subgroups: 10th (best-case), 25th (upper-typical), 50th (median), 75th (lower-typical), and 90th (worst-case). Results: The total study population comprised 27,275 patients. Twenty-five percent these patients did not receive any antitumor treatment. From 2008-2016, mOS of the total population remained unchanged at approximately 12 months. OS improved only for the upper-typical and best-case patients; by 4.2 to 29.1 months (p&lt;0.001), and by 6.0 months to 62.0 months (p&lt;0.001), respectively. No clinically relevant change was seen among patients who received systemic therapy, with mOS close to 15 months and best-case scenario approximately 40 months. mOS and worst-case scenario for survival were highest in patients who underwent both metastasectomy and systemic therapy: around 48 and 15 months, respectively. A clinically relevant improvement in survival over time was observed only in patients who initially received metastasectomy without systemic treatment. Conclusions: In contrast to the wide belief that mOS of mCRC patients receiving systemic therapy has improved substantially, improvement could not be demonstrated in our real-life population. Clinicians should consider quoting multiple scenarios for survival based on real-life data, instead of point estimates from clinical trials, when informing patients about their life expectancy.