tbuckley/cabot-search huggingface dataset:
A population-based study of morbidity after pancreatic cancer diagnosis.
Authors: Reith Sarkar, Katherine Elaine Fero, Neil Panjwani, Rayna Matsuno, James Don Murphy
Journal: Journal of Clinical Oncology (2018)

236 Background: Pancreatic cancer is characterized by early and relentless tumor spread. This leads healthcare providers to consider pancreatic cancer a “distant disease.” However, local tumor progression within the pancreas can lead to substantial morbidity. This study defines the long-term morbidity from local and non-local disease progression in a large population-based cohort. Methods: We identified 21,500 Medicare beneficiaries diagnosed with pancreatic cancer between 2000-2011 in the Survival, Epidemiology and End Results database. Hospitalizations identified from Medicare claims were attributed to complications either local (biliary, upper GI ulcer/bleed, pain, pancreatic, radiation toxicity) or non-local (thromboembolic events, any cytopenia, dehydration, nausea/vomiting/motility, malnutrition and cachexia, ascites, pathologic fracture, chemotherapy toxicity) in nature. Competing risk analyses were used to determine the cumulative incidence of complications from local, and non-local disease. Multivariable Fine-Gray models were used to identify the impact of chemotherapy or radiotherapy on the risk of hospitalization. Results: Of the total cohort 9,347 (43.5%) patients were hospitalized for a local complication, and 13,101 (52.4%) for a non-local complication. After adjusting for the competing risk of death, complication due to local disease at 24-months post-diagnosis was highest in non-metastatic non-resection (55.1%), followed by non-metastatic resection (44%) and metastatic (34.5%) patients. Non-local complications were highest in non-metastatic non-resection (60.6%), followed by metastatic (58.6%) and non-metastatic resection (52.5%) patients. Predictors of hospitalization for local and non-local complications included age, race-ethnicity, location, patient group, tumor size and diagnosis year. Radiation and chemotherapy had minimal impact on risk of hospitalization. Conclusions: Despite the widely-known predilection of distant disease spread in pancreatic cancer, local tumor progression also leads to substantial morbidity and hospitalization. Radiation and chemotherapy did not decrease the rates of hospitalization for local complications.
Pathologist characteristics associated with accuracy and reproducibility of melanocytic skin lesion interpretation
Authors: David E. Elder, Michael W. Piepkorn, Raymond L. Barnhill, Gary M. Longton, Heidi D. Nelson, Stevan R. Knezevich, Margaret S. Pepe, Patricia A. Carney, Linda J. Titus, Tracy Onega, Anna N.A. Tosteson, Martin A. Weinstock, Joann G. Elmore
Journal: Journal of the American Academy of Dermatology (2018)
Metastasis Seeding Cells: Lone Invaders or Mass Migrators?
Authors: Marco Gerlinger
Journal: Clinical Cancer Research (2018)

Lymph node metastases are among the best predictors of recurrence and of cancer-related death in early-stage colorectal cancers. Yet, despite their clinical and biological relevance, it remains elusive how lymph node metastases develop and whether metastatic seeding is a major bottleneck that restrains genetic heterogeneity of metastatic disease.
IMPACT OF CHRONIC KIDNEY DISEASE (CKD) ON IN-HOSPITAL AND 3-YEAR CLINICAL OUTCOMES IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION (AMI) TREATED BY CONTEMPORARY PCI AND OPTIMAL MEDICAL THERAPY (OMT): INSIGHTS FROM THE J-MINUET STUDY
Authors: Yukio Ozaki, Koichi Nakao, Kazuo Kimura, Ako Jynya, Teruo Noguchi, Satoshi Yasuda, Hiroshi Takahashi, Kunihiro Nishimura, Yoshihiro Miyamoto, Masaharu Ishihara
Journal: Journal of the American College of Cardiology (2018)
Myocardial Infarction After Vascular Surgery
Authors: Kamil Polok, Jakub Fronczek, Wojciech Szczeklik
Journal: JAMA Surgery (2018)

To the Editor The article by Juo et al1 addresses the important issue of temporal trends in perioperative myocardial infarction after high-risk vascular surgery. We congratulate the authors on their contribution; however, we have some reservations concerning the methods of this study.
AN INSIGHT INTO THE ETIOLOGY OF NEW INTRACARDIAC MASSES (GHOST) AFTER INFECTED LEAD EXTRACTION: A SINGLE-CENTER STUDY PERFORMED BY INTRACARDIAC ECHOCARDIOGRAPHY
Authors: Carlo Caiati, Paolo Pollice, Mario Erminio Lepera, Giovanni Luzzi, Stefano Favale
Journal: Journal of the American College of Cardiology (2018)
A phase 1 study of p53MVA vaccine in combination with pembrolizumab.
Authors: Vincent M. Chung, Ferdynand Kos, Nicola Hardwick, Yuan Yuan, Joseph Chao, Mengsha Li, Kathryn Zurcher, Paul Henry Frankel, Daneng Li, James Ross Waisman, Don J. Diamond
Journal: Journal of Clinical Oncology (2018)

206 Background: Mutations in the p53 gene are present in a majority of solid tumors, resulting in the accumulation of oncogenic and potentially immunogenic p53 protein within tumor cells. We have developed a genetically engineered Modified Vaccinia Ankara (MVA) virus to express wild type p53 transgene (p53MVA) as an immunotherapeutic strategy. We observed robust p53-specific CD8 + T cell responses which were further enhanced by anti-PD-1 treatment. This phase 1 study evaluates the safety and tolerability of the p53MVA vaccine in combination with pembrolizumab. Methods: Patients with non-small cell lung, head and neck squamous cell (HNSCC), hepatocellular (HCC), renal cell, melanoma, bladder, soft tissue sarcoma, triple-negative breast (TNBC), pancreatic (PDAC) and MSI high colorectal cancer failing or intolerant to standard treatment were eligible. Confirmation of p53 involvement by immunohistochemistry or mutational analysis was required for eligibility. A 3-at-risk rolling design was employed and patients received 5.6 x 10 8 pfu p53MVA for 3 doses in combination with 200 mg pembrolizumab for 7 doses every 3 weeks. Blood draws for immunological monitoring were obtained pre-treatment and up to week 19. Results: Two patients (TNBC and HNSCC) showed clinical benefit associated with durable p53-specific CD8 + T cell responses with gene expression pathway scores of T cell function and associated immune response categories elevated for more than 6 months. The TNBC patient had complete regression of cutaneous metastases and stable disease for &gt; 6 months. Two patients (TNBC and PDAC) were on study for 35 and 9 weeks respectively; however, p53-specific T cells were not generated. Four patients (HCC, PDAC and 2 with TNBC) had rapidly progressive disease. Conclusions: Targeting p53 antigen associated with cancer using a viral vaccine p53MVA in combination with PD-1 blockade represents a novel immunotherapeutic approach capable of stimulating systemic immune responses and associated clinical benefit. Clinical trial information: NCT02432963.
Patient groups unite to highlight Brexit concerns
Authors: Jacqui Wise
Journal: BMJ (2018)

Patients’ organisations from the UK and across Europe have written a joint letter urging Brexit negotiators to prioritise patients’ safety and access to treatment in the second phase of talks. The letter to EU chief Brexit negotiator Michel Barnier and UK state secretary for exiting the EU David Davis, from heads of 11 organisations, warns of the risk of drugs getting stuck at borders and delays to patients’ access to new treatments if collaborative research were to be curtailed and regulatory systems diverge.1 The letter, sent ahead of a European Council meeting on 22 March, sets out four priorities:
Promote GP careers to counter falling applicant numbers, says NHS England
Authors: Abi Rimmer
Journal: BMJ (2014)

Being a GP is a “phenomenal” job, and more must be done to promote it to doctors in training, said Mike Bewick, NHS England’s deputy medical director.

Bewick raised the issue during a speech at a Londonwide LMCs (local medical committees) conference on collaborative working on February 12. He said that evidence from local education and training boards showed that the number of doctors choosing general practice as a career was falling. He argued that this trend needed to be reversed and that general practice needed to be made “attractive again.”

“We …
Radium-223 and atezolizumab in platinum refractory urothelial carcinoma with bone metastases: NCT03208712.
Authors: Sarah Elizabeth Yentz, Melissa Andrea Reimers, Stephanie Daignault, Morand Piert, Ajjai Shivaram Alva
Journal: Journal of Clinical Oncology (2018)

TPS543 Background: Immunologically, radiation increases tumor antigen release, cytotoxic CD8+ T cell infiltration while reducing myeloid derived suppressor cells (MDSCs), with distant abscopal responses occasionally reported. Radium-223 is a systemically administered bone-targeted alpha emitter that causes double-stranded DNA breaks and may induce similar immune effects. Anti-PD(L1) immune checkpoint inhibitor monotherapy with Atezolizumab demonstrates objective responses in metastatic urothelial cancer. In mouse models, radiotherapy and checkpoint immune inhibitor in combination synergistically reduce tumor growth. We hypothesized that the combination of Atezolizumab and Radium-223 in metastatic urothelial cancer pts with bone metastases would target bone metastases more effectively and yield higher response rates. Methods: Eligibility criteria for this single-site, phase 2 trial of Radium-223 in combination with Atezolizumab include diagnosis of advanced urothelial carcinoma with ≥1 bone metastasis, RECIST 1.1 measurable disease, progression of disease after/on platinum-containing chemotherapy in the metastatic or perioperative setting, ECOG PS of 0-2 and adequate organ function. Twenty-two pts will be treated with Radium-223 at a dose of 55 kBq/kg IV and Atezolizumab 1200mg IV both on day 1 of 21 day cycles. Up to 6 doses of Radium-223 will be administered. Atezolizumab will be continued until lack of clinical benefit or intolerable toxicity for up to 17 cycles. Routine response assessment will be performed every 12 weeks. Primary endpoint is best overall response per RECIST 1.1. Secondary objectives are to determine the safety and tolerability; determine the overall survival, progression free survival, clinical benefit rate, complete response rate and duration of response; and changes in quality of life as assessed by the EORTC QLQ-C30 score. Exploratory objectives are PD-L1 status by IHC, changes in bone scan per EXINI bone scan index and efficacy measures by irRC. If ≥6 pts respond, corresponding to an ORR of 27% with 80% confidence limits of 15%-43%, further study of the combination would be warranted. Blood and archival tissue will be collected for correlative studies. Clinical trial information: NCT03208712.
Abstract P6-03-08: Detection ability of dedicated breast positron emission tomography for small-sized breast cancer
Authors: S Sueoka, N Masumoto, M Nishina, Y Kimura, E Suzuki, N Goda, S Sasada, K Kajitani, A Emi, R Haruta, T Kadoya, T Kataoka, M Okada
Journal: Cancer Research (2018)

Abstract Background: Whole body (WB) 18F-fluorodeoxyglucose positron emission tomography (PET) has a relatively poor spatial resolution (&amp;gt;1 cm), which limits the capability to detect small lesions. Therefore, small-sized breast cancers (≤1 cm) may not be visible on WBPET. To overcome these limitations, dedicated breast PET (DbPET) has been developed to improve spatial resolution. DbPET enables detailed high-resolution images within the breast. We aimed to determine whether DbPET can detect small-sized breast cancer compared to WBPET. Methods: We investigated 203 consecutive patients (217 tumors) (T1–3, N0–3a, M0) with breast cancer who underwent concurrent DbPET and WBPET between January 2016 and March 2017. All DbPET and WBPET images were semi-quantified based on standard uptake values. The diagnostic performance of each scanner was assessed in DbPET and WBPET. Tumors were classified based on pathological classification as follows: Tis, ductal carcinoma in situ (DCIS); T1a, ≤0.5 cm; T1b, 0.5–1 cm; and T1c, 1–2 cm; T2, 2–5 cm; T3, &amp;gt;5 cm. The sensitivities of DbPET and WBPET were compared in each size group. Results: Table 1 shows the detection rate of breast cancer in WBPET and DbPET The detection rate of breast cancer in WB- and Db-PET DbPETWBPETpTumor sizeDetection (-) n(%)Detection (+) n(%)Detection (-) n(%)Detection (+) n(%) Tis6(14.6)35(85.4)18(43.9)23(56.1)0.0030T1a2(8)23(92)7(28)18(72)0.0594T1b2(6.5)29(93.5)10(32.3)21(67.7)0.0077T1c5(8.2)56(91.8)11(18)50(82)0.1038T20(0)57(100)1(1.8)56(98.2)0.2375T30(0)2(100)0(0)2(100)-total15(6.9)202(93.1)47(21.7)170(78.3)&amp;lt;0.0001 . The overall detection rate in DBPET [93.1% (202/217)] was significantly higher than that of WBPET [78.3% (170/217)] (P &amp;lt; 0.001). For smaller tumors, DbPET was more sensitive than WBPET: Tis (85.4% vs. 56.1%), T1a (92% vs. 72%), T1b (93.5% vs. 67.7%), T1c (91.8% vs. 82%), T2 (100% vs. 98.2%), and T3 (100% vs. 100%). The sensitivity of DbPET was significantly higher than that of WBPET in Tis (P = 0.003) and T1b (P = 0.008) and tended to be higher than that of WBPET in T1a (P = 0.059). Conversely, no significant differences were observed in T1c (P = 0.103) and T2 (P = 0.238). Conclusion: The imaging sensitivity of DbPET was higher than that of WBPET. DbPET showed significant sensitivity in DCIS and tumors ≤1 cm, which is a weak point for WBPET. DbPET may serve as a new diagnostic modality to detect small-sized breast cancer. Citation Format: Sueoka S, Masumoto N, Nishina M, Kimura Y, Suzuki E, Goda N, Sasada S, Kajitani K, Emi A, Haruta R, Kadoya T, Kataoka T, Okada M. Detection ability of dedicated breast positron emission tomography for small-sized breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-03-08.
Intra-arterial idarubicin_lipiodol without embolisation in hepatocellular carcinoma: The LIDA-B phase I trial
Authors: Boris Guiu, Jean-Louis Jouve, Antonin Schmitt, Anne Minello, Franck Bonnetain, Christophe Cassinotto, Lauranne Piron, Jean-Pierre Cercueil, Romaric Loffroy, Marianne Latournerie, Maëva Wendremaire, Côme Lepage, Mathieu Boulin
Journal: Journal of Hepatology (2018)
Molecular profiles of small cell bladder and prostate cancer and comparisons with small cell lung cancer.
Authors: Nancy Ann Dawson, Daniel M. Geynisman, Earle Frederick Burgess, Bradley G. Somer, David Arguello, Ralph J. Hauke, Daniel A. Vaena, Derek Raghavan, Elisabeth I. Heath
Journal: Journal of Clinical Oncology (2018)

264 Background: Small cell bladder cancer (SCBC) and small cell prostate cancer (SCPC) are rare and aggressive cancers. Standard therapy remains a platinum agent combined with etoposide, with few options after recurrence. Advances in molecular genomics and drug development have altered our approach to cancer. These same novel approaches may alter how we approach SCBC and SCPC. The purpose of this study is to identify potential targets and compare molecular profiles of SCBC and SCPC to SCLC. Methods: In total, 21 SCBC and 19 SCPC were identified from a de-identified database (Caris Life Sciences). Specimens were evaluated for genetic aberrations (Sanger or next generation sequencing [NGS], ISH) and/or protein expression (immunohistochemistry [IHC]). Comparisons were made against a de-identified cohort of SCLC (n = 428). Results: Pathogenic/presumed pathogenic mutations in SCBC were found in TP53 (91.7%, 11/12), RB1 (18.2%, 2/11), PTEN (8.3%, 1/12), EGFR (7.7%, 1/13), and PIK3CA (7.1%, 1/14). SCPC genetic aberrations were detected in TP53 (72.7%, 8/11) and RB1 (25.0%, 2/8). No carcinomas in this cohort had a high mutational burden or MSI-high status (0%, 0/7). Amplified genes found in SCBC included DDR2 (50%, 1/2) and EGFR (25.0%, 1/4). In SCPC, gene amplification was found in AKT2 (20%, 1/5), CCNE1 (20%, 1/5), FGFR1 (20%, 1/5), and MYC (20%, 1/5). The highest protein expression rates in SCBC involved MRP1 (100%, 5/5), TOP2A (94.1%, 16/17), and RRM1 (81.3%, 13/16). The highest protein expression rates in SCPC were MRP1 (100%, 6/6), TUBB3 (100%, 9/9), and TOP2A (94.4%, 17/18). Comparisons between SCBC and SCPC with SCLC revealed more similarities than differences. Significant differences were found in RRM1 by IHC between SCBC and SCLC. Also, significant differences were found between SCPC and SCLC in AR and PTEN by IHC. Conclusions: Comparisons of GU small cell carcinomas reveal similarities to SCLC. Both TP53 and RB1 mutations were found in both SCBC and SCPC. Amplification in genes CCNE1 and FGFR1, frequently identified in SCLC, were also found in SCPC. The high protein expression in biomarkers like MRP1 may explain the poor response to cytotoxic chemotherapy. Prospective studies are urgently needed.
An Inflammatory Environment: Donor Granulocytes Mediate Endothelial Regeneration Following Transplantation
Authors: Michael D. Milsom
Journal: HemaSphere (2018)

The kinetics of hematopoietic reconstitution following stem cell transplantation is a clinically import parameter. While extensive research has focused on cell autonomous factors that can impact on reconstitution capacity of donor hematopoietic stem cells (HSCs), comparatively little work has focused on regeneration of the bone marrow niche components that are also damaged following treatment with myeloablative conditioning agents. In a recent article in Nature Medicine, the group of Daniel Lucas used the mouse transplantation model to explore the degree to which the bone marrow endothelial niche regenerates after total body irradiation, and whether this impacts upon hematopoietic reconstitution. Surprisingly, they found that donor bone marrow granulocytes were able to improve the recovery of endothelial cells following irradiation, resulting in enhanced hematopoietic engraftment (Fig. 1). On a mechanistic level, the authors discovered that the key signaling molecule mediating this effect was granulocyte-derived tumor necrosis factor-α (TNF-α), which has previously been ascribed both positive and negative effects on HSCs. Not only does this article uncover a completely new indirect mechanism via which TNF-α may impact on HSC biology, but it also highlights a potential novel approach to improve bone marrow transplantation by focusing on enhancing the recovery of the HSC niche.Figure 1: Immunofluorescence image showing the association between transferred granulocytes (white, Ly6G) with regenerating sinusoids (red, CD31/CD144) and arterioles (red and green, CD31/CD144 + Nestin-GFP bright ) in Nestin-gfp recipients 6 days after lethal irradiation and transplantation. Scale bar = 50 μm. Image provided by Daniel Lucas, University of Michigan School of Medicine.Link to article: https://www.nature.com/articles/nm.4448.
Surgical training posts could be reduced to avoid an oversupply of consultants
Authors: Abi Rimmer
Journal: BMJ (2016)

The number of trainees accepted into general surgical training could be reduced to avoid an oversupply of consultant surgeons, the Centre for Workforce Intelligence (CFWI) said.

It calculated that Health Education England would need to change the number of trainees entering general surgery specialty training level 3 (ST3) in 2018 to avoid a future oversupply. 

The CFWI said that if national recruitment …
Abstract P4-13-05: Detection of local recurrence in premenopausal patients treated with neoadjuvant chemotherapy and mastectomy with or without breast reconstruction
Authors: CE Jacobson, M Kozak, E Walck, E Hawley, K Horst
Journal: Cancer Research (2018)

Abstract Background: Women who undergo mastectomy for breast cancer treatment often undergo implant based or autologous reconstruction. There are limited data, however, as to whether reconstruction may interfere with detection of a locoregional recurrence. The goal of this study was to assess whether women who undergo reconstruction after mastectomy have an increased risk of local recurrence and/or longer time to local recurrence detection. Methods: One hundred and fifty-four premenopausal patients who underwent neoadjuvant chemotherapy followed by mastectomy were identified between 2005 and 2015. Patients with de novo Stage IV disease or insufficient medical records were excluded from analysis. Patient and treatment variables were collected, including clinical stage, type of chemotherapy, type of surgery and reconstruction, use of postmastectomy radiotherapy, and use of endocrine therapy. Local recurrence (LR) was defined as a chest wall or skin recurrence. Regional failure (RF) was defined as recurrence in the axilla, supraclavicular fossa, or internal mammary nodes. Results: The median follow up for this cohort was 49.9 months. Of the 154 patients, 71 (46%) underwent unilateral mastectomy and 83 (54%) underwent bilateral mastectomies. Thirty patients (19%) elected to forgo reconstruction while 78 (51%) received tissue expander/implant based reconstruction, 29 (19%) received autologous reconstruction, and 17 (11%) had unknown reconstruction histories. Patients who had reconstruction had an increased time to detection of a LR compared to those without reconstruction (p=0.048). However, controlling for the T and N stage of disease, Cox regression demonstrated no observable difference in risk for LR between patients who underwent reconstruction compared to those who didn't. There was no difference in detection of RF between those with and without reconstruction (p=0.092). Conclusions: Premenopausal patients treated with neoadjuvant chemotherapy followed by mastectomy with any type of reconstructive surgery had an increased time to local recurrence detection compared to those without reconstruction. There was no difference in the risk for local recurrence between those who underwent reconstruction compared to those who didn't. Citation Format: Jacobson CE, Kozak M, Walck E, Hawley E, Horst K. Detection of local recurrence in premenopausal patients treated with neoadjuvant chemotherapy and mastectomy with or without breast reconstruction [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-13-05.
A human bone marrow mesodermal-derived cell population with hemogenic potential
Authors: Saloomeh Mokhtari, Evan Colletti, Weihong Yin, Chad Sanada, Zanetta Lamar, Paul J. Simmons, Steven Walker, Colin Bishop, Anthony Atala, Esmail D. Zanjani, Christopher D. Porada, Graça Almeida-Porada
Journal: Leukemia (2018)