tbuckley/cabot-search huggingface dataset:
Comprehensive genomic sequencing of high-grade neuroendocrine neoplasms.
Authors: Thomas Yang Sun, Paul Van Hummelen, Brock Martin, Charlie Xia, Hojoon Lee, Lan Zhao, Kathleen Hornbacker, Hanlee Ji, Pamela L. Kunz
Journal: Journal of Clinical Oncology (2020)

624 Background: Grade 3 neuroendocrine neoplasms (G3 NENs), if poorly differentiated, have a median survival of only 10-19 months. Little is known regarding their underlying genomics. Methods: We applied multiomics analysis to 46 cases of G3 NEN that included copy number analysis, whole exome, and transcriptomic sequencing. Results: Of the 46 unique cases, 17 were lung, 16 gastroenteropancreatic (GEP), 13 other; 5 well-differentiated, 39 poorly differentiated and 2 mixed. Using a multivariate Cox model, we found histology characteristics (including differentiation, Ki67 and mitotic index) did not correlate with changes in overall survival (OS). The clinical variables that did correlate with OS included: number of lines of treatment (hazard ratio for death [HR], 0.72; p &lt; 0.05), GEP primary site (HR, 5.36; p &lt; 0.005), and non-resected primary tumor (HR, 14.52; p &lt; 0.001). Two copy number changes were associated with worse prognosis: focal deletion 22q13 (HR, 10.23; p &lt; 0.005), and arm amplification 19q (HR, 7.09; p &lt; 0.01). The median OS of the top quartile compared to the rest for 22q13 deletion carriers was 9.9 months vs. 24 months, and for 19q amplification carriers was 8.7 months vs. 36.7 months. We estimated a median tumor mutation burden (TMB) of 3.7 mutations/Mb, with 20% (8/40) of patients showing high TMB ( &gt; 10 mutations/Mb). The top five mutated genes were USH2A, RB1, APC, TP53, and MUC16. We also observed high transcriptomic similarity across all NENs regardless of their site of origin. Conclusions: We identified two copy number changes that can serve as predictive biomarkers in G3 NENs, as they confer an increased risk of death by as high as 10x to the carriers. Further, G3 NENs are characterized by a distinct group of somatic mutations, and a significant number have high tumor mutation burden. Lastly, G3 NENs across different organs were relatively homogeneous in expression profile.
ドキソルビシン(DOX)抵抗性腫瘍もつマウスにおけるPEGリポソーマルDOXのin vivo抗腫瘍作用:血管内皮細胞に対する細胞毒性作用の関与
Authors: Ogawara Ken-ichi, UN Keita, Tanaka Ken-ichi, Higaki Kazutaka, Kimura Toshikiro
Journal: Journal of Controlled Release (2009)
Forging a New Frontier: Providing Palliative Care to People With Cancer in Rural and Remote Areas
Authors: Marie Bakitas, Kristen Allen Watts, Emily Malone, J. Nicholas Dionne-Odom, Susan McCammon, Richard Taylor, Rodney Tucker, Ronit Elk
Journal: Journal of Clinical Oncology (2020)

Mounting evidence supports oncology organizations' recommendations of early palliative care as a cancer care best practice for patients with advanced cancer and/or high symptom burden. However, few trials on which these best practices are based have included rural and remote community-based oncology care. Therefore, little is known about whether early palliative care models are applicable in these low-resource areas. This literature synthesis identifies some of the challenges of integrating palliative care in rural and remote cancer care. Prominent themes include being mindful of rural culture; adapting traditional geographically based specialty care delivery models to under-resourced rural practices; and using novel palliative care education delivery methods to increase community-based health professional, layperson, and family palliative expertise to account for limited local specialty palliative care resources. Although there are many limitations, many rural and remote communities also have strengths in their capacity to provide high-quality care by capitalizing on close-knit, committed community practitioners, especially if there are receptive local palliative and hospice care champions. Hence, adapting palliative care models, using culturally appropriate novel delivery methods, and providing remote education and support to existing community providers are promising advances to aid rural people to manage serious illness and to die in place. Reformulating health policy and nurturing academic-community partnerships that support best practices are critical components of providing early palliative care for everyone everywhere.
A nationwide population-based study comparing survival in unresectable advanced or synchronous metastatic esophageal and gastric adenocarcinoma.
Authors: Marieke Pape, Pauline A.J. Vissers, David Bertwistle, Laura McDonald, Hanneke W.M. Van Laarhoven, Rob H. A. Verhoeven
Journal: Journal of Clinical Oncology (2020)

308 Background: Similarities between esophageal and gastric adenocarcinomas have been identified in terms of genomic characteristics. There is however no consensus on the combined or stratified inclusion of esophageal adenocarcinoma (EAC) within gastric cancer (GC) clinical trials. The aim of our study was to compare patient and tumor characteristics, first-line treatment regimens and overall survival (OS) of patients with EAC and GC. Methods: We selected patients with unresectable advanced and/or synchronous metastatic EAC (n = 1554) or GC (including junction tumors; n = 2095) diagnosed in the period 2015-2017 from the nationwide Netherlands Cancer Registry. Patients with a positive HER2 test result and/or receiving trastuzumab as a first-line treatment were excluded. Data on OS were analyzed using Kaplan-Meier curves with Log-Rank test. Results: The EAC patient population had significantly more male patients (83% vs 66%), lower median age (68 vs 71 years) and higher median BMI (25.4 vs 24.5). Significant differences in location of metastases were identified, with higher percentages in non-regional lymph nodes (48% vs 28%), liver (50% vs 35%), lung (21% vs 9%) and bone (19% vs 7%) and lower in peritoneum (5% vs 42%), in EAC versus GC patients respectively. EAC patients more often received any type (supportive or active systemic) of treatment (76% vs 60%). Median OS was longer in EAC than GC patients (EAC: 4.8 vs GC: 4.1 months; p &lt; 0.01). The percentages of patients receiving first-line systemic treatment were equal in both groups (43%). The number of patients receiving CapOx or FOLFOX was not significantly different (43% vs 47%). Carboplatin+paclitaxel was more frequently given in EAC versus GC (34% vs 3%), while EOX or ECC was given less frequently (12% vs 30%). No significant difference was observed in median OS between EAC and GC patients receiving first-line active systemic treatment (8.0 vs 7.6 months; p = 0.28). Conclusions: Patient characteristics, tumor characteristics, treatment regimens and OS differ between EAC and GC patients. Despite these differences, in patients receiving first-line active systemic treatment no significant differences in OS were found.
Menopausal Estrogen-Alone Therapy and Health Outcomes in Women With and Without Bilateral Oophorectomy
Authors: JoAnn E. Manson, Shari S. Bassuk
Journal: Annals of Internal Medicine (2020)

Letters4 February 2020Menopausal Estrogen-Alone Therapy and Health Outcomes in Women With and Without Bilateral OophorectomyJoAnn E. Manson, MD, DrPH and Shari S. Bassuk, ScDJoAnn E. Manson, MD, DrPHBrigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (J.E.M.)Search for more papers by this author and Shari S. Bassuk, ScDBrigham and Women's Hospital, Boston, Massachusetts (S.S.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0680 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Women who have had early bilateral oophorectomy may be at increased risk for premature coronary heart disease, osteoporosis, and other adverse health outcomes. As Dr. Sarrel notes, current guidelines recommend treating these women with estrogen therapy until at least the average age of natural menopause (that is, 51 years). We agree. After that age, some women may experience a favorable benefit–risk ratio by continuing this therapy at least through their 50s if they have vasomotor symptoms or other indications for treatment and do not have contraindications. Clinical decision making about the use of estrogen therapy must weigh patient-specific ... Author, Article, and Disclosure InformationAffiliations: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (J.E.M.)Brigham and Women's Hospital, Boston, Massachusetts (S.S.B.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-0274. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMenopausal Estrogen-Alone Therapy and Health Outcomes in Women With and Without Bilateral Oophorectomy JoAnn E. Manson , Aaron K. Aragaki , Shari S. Bassuk , Rowan T. Chlebowski , Garnet L. Anderson , Jacques E. Rossouw , Barbara V. Howard , Cynthia A. Thomson , Marcia L. Stefanick , Andrew M. Kaunitz , Carolyn J. Crandall , Charles B. Eaton , Victor W. Henderson , Simin Liu , Juhua Luo , Thomas Rohan , Aladdin H. Shadyab , Gretchen Wells , Jean Wactawski-Wende , Ross L. Prentice , and Menopausal Estrogen-Alone Therapy and Health Outcomes in Women With and Without Bilateral Oophorectomy Philip Sarrel Metrics Cited byRecent Progress on Luminescent Metal-Organic Framework-Involved Hybrid Materials for Rapid Determination of Contaminants in Environment and Food 4 February 2020Volume 172, Issue 3Page: 227KeywordsCoronary heart diseaseDecision makingDisclosureEstrogensMenopauseOophorectomyOsteoporosis ePublished: 4 February 2020 Issue Published: 4 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The clinical utility of the 2017 Fukuoka Guidelines and 2015 American Gastroenterological Association Guidelines for the management of intraductal papillary mucinous neoplasms.
Authors: Gandhi Lanke, Donald Campbell, Emmanuel Coronel, Manoop S. Bhutani, Brian Weston, William A. Ross, Michael Paul Kim, Graciela M. Nogueras-Gonzalez, Matthew H. G. Katz, Jeffrey H. Lee
Journal: Journal of Clinical Oncology (2020)

640 Background: Mucinous cystadenocarcinoma are malignant and mucinous pancreatic cysts (PC) have malignant potential. The management of PC remains controversial despite consensus guidelines. This study aims to evaluate the clinical utility of the 2017 Fukuoka Guidelines (FG) and 2015 American Gastroenterological Association Guidelines (AGA-G) for the management of PC. Methods: 212 patients who underwent EUS for PC between 2010 and 2017 were identified. The FG and AGA-G were used to define worrisome and high-risk cyst features. Receiver Operating Characteristic (ROC) curve was used to define sensitivity (SN), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV). Results: 141 of 212 patients had IPMNs.EUS-FNA was performed in 76.5% with no reported complications. Median follow-up was 4.2 years. The majority of the IPMNs were in the pancreatic head (44.7%) or body (39.7%) while only 15.6 % were in the tail. Using the FG, 46.1% had at least one worrisome feature (FG-W) and 7.1% had at least one high risk feature (FG-HR). Using the AGA-G, 28.4% had at least one HR feature (AGA-HR1) and 1.4% patients had two or more risk factors (AGA-HR2). A change in cyst character (increase of &gt; 5 mm in 2 years, development of a solid component, or new pancreatic duct dilation) was noted in 43.2% patients. The median time to cyst change was 21 months. For prediction of cyst changes, the FG-W had a SN of 45.8%, SP of 55.4%, PPV 45%, and NPV 56%. FG-HR had a SN of 14.3%, SP of 53.2%, PPV 1.7%, and NPV 91.8%. AGA-HR1 had a SN of 35.3%, SP of 51.5%, PPV 20%, and NPV 69.9%. AGA-HR2 had a SN of 0%, SP of 54.2%, PPV 0%, and NPV 97.3%. No difference was seen in cyst change or development of high risk or worrisome features with CEA &gt; 192 vs. &lt; 192 (p = 0.99). During follow up, 14 patients died, but only one patient died of pancreatic cancer. Conclusions: FG and AGA-G are difficult to validate because malignant cyst transformation is rare. There was no correlation between any cyst characteristics on EUS and cyst changes. FG-W had the best performance in predicting changes. Surgical candidates should be carefully selected, as these guidelines have a limited clinical utility.
Association of <i>KRAS</i> and <i>BRAF</i> mutations with progression-free survival (PFS) with second-line FOLFIRI +/- regorafenib in metastatic colorectal cancer (mCRC).
Authors: Federico Innocenti, Sara R. Selitsky, Joel S. Parker, James Todd Auman, Kelli Hammond, Sushant A. Patil, Hanna Kelly Sanoff, Michael Sangmin Lee
Journal: Journal of Clinical Oncology (2020)

196 Background: LCCC1029 was a 2:1 randomized phase II trial of 2nd-line FOLFIRI plus either regorafenib or placebo in mCRC. The addition of regorafenib improved PFS (median PFS 6.1 vs 5.3 mo, HR 0.73, 95% CI 0.53-1.01). However, the effect of somatic mutations on regorafenib activity has not been tested. Methods: We performed whole exome sequencing on archival primary tumor tissue and paired normal tissue in 85 patients of LCCC1029. We compared PFS and OS using Kaplan-Meier method and log-rank tests, and hazard ratios (HR) were estimated using Cox proportional hazards method. Results: Among the 85 subjects, 54 (64%) had tumors wild-type (WT) for KRAS and BRAF, 26 (31%) had tumors with KRAS mutations in exons 2-4, and 5 (6%) had tumors with BRAF V600E. The addition of regorafenib to FOLFIRI improved PFS in the KRAS/ BRAF WT subgroup (median PFS 8.0 vs 4.9 mo, HR 0.68, 95% CI 0.48-0.97, log-rank p=0.028), but not in the KRAS mutant subgroup (median PFS 6.8 vs 5.5 mo, HR 0.90, 95% CI 0.61-1.35, log-rank p=0.617) or the BRAF mutant subgroup (log-rank p=0.156). In all of these subgroups, the addition of regorafenib was not associated with significant difference in OS. BRAF V600E was prognostic and associated with significantly worse OS (median OS 8.4 vs 18.0 mo, HR 2.59, 95% CI 1.01-6.66, log-rank p=0.04). Conclusions: The addition of regorafenib to FOLFIRI improves PFS among the subgroup of patients with KRAS and BRAF dual WT CRC, but not among the KRAS mutant subgroup. These results indicate that the addition of anti-angiogenic therapy to second-line chemotherapy backbones may be more effective in KRAS/ BRAF WT tumors in particular. More confirmatory studies are needed to corroborate this finding.
Seroprevalence of hepatitis E virus among blood donors on Corsica, France, 2017
Authors: Lisandru Capai, Nathanaël Hozé, Jacques Chiaroni, Sylvie Gross, Rachid Djoudi, Rémi Charrel, Jacques Izopet, Frédéric Bosseur, Stéphane Priet, Simon Cauchemez, Xavier de Lamballerie, Alessandra Falchi, Pierre Gallian
Journal: Eurosurveillance (2020)

BackgroundHepatitis E virus (HEV) is an emerging zoonotic pathogen and an important cause of acute viral hepatitis in European countries. Corsica Island has been previously identified as a hyperendemic area for HEV.AimOur aim was to characterise the prevalence and titres of IgG antibodies to HEV among blood donors on Corsica and establish a model of the annual force of infection.MethodsBetween September 2017 and January 2018, 2,705 blood donations were tested for anti-HEV IgG using the Wantai HEV IgG enzyme immunoassay.ResultsThe overall seroprevalence was 56.1%. In multivariate analysis, seroprevalence was higher in men than in women (60.0% vs 52.2%; p < 0.01), increased with age and was significantly higher among donors born on Corsica (60.6% vs 53.2%; p < 0.01). No significant difference was observed between the five districts of the island. IgG anti-HEV titres were mostly low (70% of positive donors had titres < 3 IU/mL). In Corsican natives, increasing seroprevalence by age could be explained by models capturing a loss of immunity (annual probability of infection: 4.5%; duration of immunity: 55 years) or by age-specific probabilities of infection (3.8% for children, 1.3% for adults).ConclusionWe confirmed the high HEV seroprevalence on Corsica and identified three aspects that should be further explored: (i) the epidemiology in those younger than 18 years, (ii) common sources of contamination, in particular drinking water, that may explain the wide exposure of the population, and (iii) the actual protection afforded by the low IgG titres observed and the potential susceptibility to secondary HEV infection.
Improved surgical margins with neoadjuvant versus adjuvant chemotherapy in clinical stage I resectable pancreatic adenocarcinoma: A National Cancer Database study.
Authors: Geoffrey Bellini, Samit Kumar Datta, Nicholas Sich, Maharaj Singh, James Leighton Weese, Federico Augusto Sanchez, Nalini Guda, Wesley Allan Papenfuss, Aaron Chevinsky
Journal: Journal of Clinical Oncology (2020)

651 Background: A strengthening consensus exists for neoadjuvant therapy (NAT) in borderline resectable pancreatic adenocarcinoma (PA), but the utilization of NAT in resectable stage I PA remains controversial. Many cancer centers are using NAT for these patients (pts), but others continue to offer upfront surgery and adjuvant therapy (AT). We hypothesized that NAT would improve margin negative resection in clinical stage I resectable PA. Methods: We utilized the IRB approved 2016 national cancer database for pancreas to establish a cohort of stage I PA pts. We divided this subset into pts who underwent NAT vs AT. We compared demographics. Primary endpoint was surgical margins. Results: 10,453pts from 2004 to 2016 had clinical stage I resectable PA: 8483pts (81.1%) AT and 1970pts (18.9%) total or partial NAT. There was a statistical difference in age (64.9 ± 9.9years NAT and 66.2 ± 9.9years AT, p&lt;0.001), but no difference in Charlson comorbidity score (p=0.1693). NAT pts had significantly higher margin negative resection rates (84.5%) than AT pts (79.4%) (p&lt;0.0001). Final pathologic staging was available for 10,237 pts: 8369 (81.8%) AT and 1868 (18.2%) NAT. Significantly fewer pts were upstaged on final pathology to stage II or greater (73.5%) in the NAT group than the AT group (84.1%) (p&lt;0.001). Conclusions: NAT leads to significantly higher margin negative rates for resectable clinical stage I PA than surgery followed by AT. The majority of pts for both groups were upstaged suggesting that we continue to clinically understage the majority of pts. Overall, total or partial NAT for clinical stage I resectable PA provides a better chance for margin negative resection. Further study in the form of a randomized control trial is necessary. [Table: see text]
John Andrew Kennedy
Authors: Ross Lorimer, Frank Dunn
Journal: BMJ (2020)

John Andrew Kennedy (“JAK”), who has died at the age of 84, was a distinguished physician, innovative cardiologist, accomplished sportsman, and dedicated family man.

John was the son of John and Christina. He was born and brought up in Stirling and educated at Stirling High School. John proudly referred to himself as a “True Son of the Rock.” His father died from cardiovascular disease when John was just 15 years old, and it is likely that this was a factor in his decision to study medicine and then cardiology. He entered the University of Glasgow in 1953, graduating in 1959. During that time he was awarded the McFarlane and Burns prizes in medicine and the McEwan medal in …
Long-term safety and efficacy of lanreotide treatment in Japanese patients with neuroendocrine tumors: Final analysis of a phase II open-label extension study.
Authors: Tetsuhide Ito, Seiichi Hisamatsu, Akihiro Nakajima, Akira Shimatsu
Journal: Journal of Clinical Oncology (2020)

621 Background: Lanreotide autogel 120mg (lanreotide) was approved in Japan in July 2017 for the treatment of gastroenteropancreatic neuroendocrine tumors (NETs) based on the results from an international phase III study (CLARINET study) and a Japanese single-arm phase II study. The CLARINET extension study demonstrated long-term efficacy and safety of lanreotide treatment; however, no Japanese patients were included in the study. To describe the safety and efficacy of long-term lanreotide treatment for NETs in Japanese patients, the final analysis of the Japanese phase II study and its extension study was performed. Methods: This open-label extension study (Study 002, JapicCTI-142698) enrolled patients who completed 48 weeks of treatment with 4-weekly subcutaneous lanreotide in an open-label phase II study in Japanese patients with NETs (Study 001, JapicCTI-132375). Study 002 had the same design as Study 001. Results: Of the 32 patients who started treatment with lanreotide, 17 completed Study 001 and enrolled in Study 002. In the safety analysis set (n = 17), 16 patients (94.1%) developed adverse events (AEs) that were considered drug-related (adverse drug reactions; ADRs), most commonly faeces pale (n = 5; 29.4%), injection site induration (n = 4; 23.5%), flatulence and diabetes mellitus (both n = 3; 17.6% each). No patient permanently discontinued lanreotide or died as a result of an AE. Four patients had a total of eight serious AEs; of these, two events of bile duct stones were considered to be ADRs. In the efficacy analysis set (n = 28), the median lanreotide exposure over Studies 001 and 002 was 52.7 weeks (range: 12–181 weeks). The best overall response was partial response in 2 patients (7.1%; reached at 60 and 108 weeks), stable disease in 20 patients (71.4%) and progressive disease in 6 patients (21.4%). Conclusions: No unexpected serious AEs developed during prolonged use of lanreotide. Lanreotide was effective over long-term treatment in Japanese patients with NETs. Clinical trial information: JapicCTI-132375, JapicCTI-142698.