tbuckley/cabot-search huggingface dataset:
Clinicopathologic characteristics and management trends of cutaneous melanoma among older patients: A National Cancer Data Base (NCDB) analysis.
Authors: Vijaya Raj Bhatt, Rajesh Shrestha, Jairam Krishnamurthy, Kailash Mosalpuria, Fausto R. Loberiza, Apar Kishor Ganti, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2014)

9059 Background: The incidence and mortality of elderly melanoma are expected to increase. Prior studies have shown poor outcomes in elderly melanoma patients. Methods: This is a retrospective study of adult patients diagnosed with cutaneous melanoma between 2000 and 2011 in the NCDB. NCDB contains ~70% of new cancer diagnosis from >1,500 American College of Surgeons-accredited cancer programs in the US and Puerto Rico. Characteristics and management of elderly melanoma (≥60 years) was compared to younger patients (20-59 years) using Chi-square test. Results: Of 476,623 total cases, 54% (n=258,153) were diagnosed among older patients. The annual incidence in the older patients increased by 174% (15,910 in 2000 vs. 27,669 in 2011). The majority were white (96%), males (65%), early-stage disease (75% stage 0-II), superficial spreading melanoma histology (39%), and received care in non-academic centers (70%). Elderly patients, compared to younger patients, were more likely to be male, and have in-situ melanoma, less likely to have nodal metastases, receive care in academic centers, undergo wide excision or major amputation for stage I-III disease and systemic therapy for stage III and IV disease (all p<.0001; Table). Conclusions: Our study demonstrates a near-doubling of the incidence of melanoma in elderly in the last decade, which disproportionately affects white men. To our knowledge, this is the largest study to demonstrate that the elderly melanoma patients are less likely to receive care in academic centers, undergo wide-excision for stage I-III disease and receive systemic therapy for Stage III-IV. Particularly, the utilization of systemic therapy was markedly lower. All or some of these health care discrepancies may contribute to decreased survival of elderly patients with melanoma. Characteristics of melanoma patients1. Variables 20-59 yrs (%) ≥60 yrs (%) Men 49 65 In-situ melanoma 21 28 Lentigo maligna 4 13 Superficial spreading melanoma 26 16 Nodal metastases in stage I-III 9 7 Care in academic centers 35 30 Wide excision or amputation, stage I-III 72 68 Systemic therapy, stage III 45 18 Systemic therapy, stage IV 50 30 1P-values for all the comparisons are <0.0001.
Pancreatic circulating tumor cells: Where are they?
Authors: Leila Khoja, Christy Mitchinson, Damien Brown, Cong Zhou, Karen Morris, Derek O'Reilly, Rahul Deshpande, Nicola de Liguori Carino, Glen Clack, Andrew M. Hughes, Juan W. Valle, Caroline Dive
Journal: Journal of Clinical Oncology (2012)

e21037 Background: We previously demonstrated that circulating tumor cell (CTC) numbers in advanced pancreatic carcinoma were low in contrast to other epithelial carcinomas. We hypothesized that pancreatic CTCs may sequest in the liver and conceived a study to explore CTC number in the peripheral and portal circulations of patients undergoing Whipple’s surgery. Methods: Seventeen patients undergoing Whipple’s surgery were recruited prospectively after informed written consent. Blood was collected intra-operatively from the portal vein prior to tumor mobilization and from the peripheral circulation. Paired samples were analysed for CTC number (CellSearch system, Veridex, USA), and M30/M65 biomarkers of cell death. Results: Of 17 patients 6 had cholangiocarcinomas and 11 had pancreatic adenocarcinomas (5 inoperable). CTC number in the portal circulation was consistently higher than in the peripheral circulation. All patients with cholangiocarcinoma had no CTCs in the peripheral circulation but two patients had 139 and 21 CTCs in the portal circulation. Five patients with pancreatic carcinoma had no CTCs in the peripheral circulation but 1 CTC in 2 patients, 4 CTCs in 2 patients and 32 and 731 CTCs were seen in 2 other patients in the portal circulation. Five patients had no CTCs in both circulations and the remaining patient had 1 CTC in the peripheral circulation and 4 CTCs in the portal circulation. Where present, circulating tumour microemboli were detected in the portal circulation only. M65 levels were higher in the portal circulation indicating higher levels of cell death. M30 levels did not differ significantly between circulations but appeared to correlate with portal CTC number. Conclusions: This is the first study to enumerate CTCs in peripheral and portal circulations in pancreato-biliary carcinomas. Higher CTC numbers are present in the portal circulation suggesting CTC sequestration in the liver. Five patients with pancreatic cancer (2 of whom were inoperable) had no CTCs in either circulation, a finding consistent with the poor vascularity and dense stromal characteristics of this carcinoma. Nonetheless the portal circulation may be a potential source for CTC characterisation including genomic analysis to further define tumor biology.
Patient experience and attitudes toward addressing the cost of breast cancer care.
Authors: Blair Billings Irwin, Yousuf Zafar, Ivy Altomare, Gretchen Genevieve Kimmick, P. Kelly Marcom, Kevin Houck, Jeffrey M. Peppercorn
Journal: Journal of Clinical Oncology (2013)

6551 Background: The American Society of Clinical Oncology has suggested that patient-physician discussion of costs is a component of high quality care. Little data exists on patients’ experience confronting costs or attitudes on how cost should be addressed. Methods: We distributed a self-administered anonymous paper survey to consecutive patients with breast cancer presenting for a routine visit within 5 years of diagnosis at an academic center. Survey questions addressed financial distress, experience and preferences concerning discussions of cost, and views on cost control. Results are primarily descriptive, with comparison among patients on the basis of disease stage using Fisher’s exact test. All p-values are 2-sided. Results: We surveyed 134 patients (response rate 86%). Median age was 61. 72% stage I-III disease, and 28% (n=36) had stage IV disease. 44% (n=57) reported at least a moderate level of financial distress. Only 14% (n=18) reported ever discussing costs with their doctor, though 94% (n=121) felt doctors should talk to patients about costs. 53% (n=69) felt doctors should discuss direct costs with patients but only 38% (n=49) felt doctors should consider costs to society or insurance companies in their decision-making. Patients with metastatic disease were significantly less likely than those with earlier stage disease to want doctors to consider societal costs (33% (n=24) vs 6% (n=2), p&lt;0.01). 88% (n=114) reported concern over costs of cancer care, but there was no consensus on how to control costs. Only 3% (n=4) favored greater cost sharing and 9% (n=11) supported greater means testing. A minority (33%, n=43) supported reducing drug costs through government price controls (33% n=43). The majority endorsed generic substitution (59%, n=75) and preferential selection of drugs which prolong survival 53% (n=69). Conclusions: Although many patients with breast cancer want to discuss costs of care with their doctors, there is little consensus on the ideal content of these discussions. Few patients support consideration of societal costs in clinical decision-making. Further research is needed to evaluate the potential for patient-physician discussions of cost to contribute to affordable high quality cancer care.
Randomized controlled phase II trial of simvastatin (SIM) as prophylaxis against radiation (RT)-induced skin toxicity (tox) in breast cancer (BC).
Authors: Shibu Joseph, Glenys Round, Jenny May Boyd, Michael B. Jameson
Journal: Journal of Clinical Oncology (2015)

e12045 Background: Statins reduce BC recurrence in retrospective clinical studies and inhibit early and late skin tox of RT in some preclinical studies. RT induces endothelial cell activation and expression of E-selectin, which binds neutrophils and monocytes, contributing to skin inflammation. Statins inhibit RT induction of E-selectin and interrupt the inflammatory cascade at an early stage. This study explored the efficacy of SIM in reducing acute skin tox of adjuvant RT in BC patients (pts). Methods: Randomised open-control phase 2 trial of SIM 40mg daily during and for 3 weeks after RT. Eligibility: women with resected invasive BC or in-situ carcinoma (CIS); RT to whole breast +/- regional nodes; RT schedules 50Gy/25 #, 45Gy/20#, 42.5Gy/16 # or 40Gy/15# +/- boost; no concurrent chemotherapy; no prior statins within 6 weeks. Stratification by surgery, boost and fraction size ≤ 2 Gy vs > 2 Gy). Primary endpoint: incidence of > grade 1 (RTOG) acute RT-related skin tox (blinded assessment). Secondary endpoints included time to skin tox, need for topical treatment, compliance with SIM, SIM-related tox, breast discomfort and fatigue. Statistical design: 130 pts gives 90% power (1p = 0.20) to detect a reduction in > grade 1 acute skin tox from 55% to 35%. Results: 81 pts were recruited over 19 months, median age 55 (range 31-84) years, 75 with invasive BC, 58 N0, 65 treated by breast-conserving surgery and 39 had prior chemotherapy. RT (+ boost) was given as 40Gy/15# in 63 (25) pts and 50Gy/25# in 18 (5) pts. 41 pts were randomised to SIM, 39 to control and 3 withdrew consent before starting RT or SIM. Blinded analysis after completion of RT by 55 pts showed much less skin tox than expected so recruitment was halted for futility. By ITT analysis > grade 1 skin tox was seen in 18% of controls and 24% with SIM 2 weeks after RT (Fisher’s exact test p = 0.57), and at any time in 39% of controls and 49% with SIM (p = 0.49). No subgroups appeared to benefit from SIM though it was well-tolerated. Conclusions: The rate of > grade 1 skin tox from RT was not reduced by SIM in this cohort, though the incidence was lower than expected in controls compared to a previous study conducted up to 2009, possibly due to change in RT fractionation. Clinical trial information: ACTRN12612000662864.
Local and systemic antitumor effects of activated autologous dendritic cells for intratumoral injection: A phase I/II trial.
Authors: Vivek Subbiah, Ravi Murthy, Omar Kayaleh, Marnix Leo Bosch
Journal: Journal of Clinical Oncology (2014)

TPS3133 Background: Dendritic cells (DC) are antigen presenting cells proficient in inducing de novo immune responses, and the presence of intratumoral DCs confers a survival advantage to patients, likely due to an improved balance between the immune system and the growing tumor lesion. We have initiated a Phase I/II clinical trial to exploit this finding, by using partially activated autologous DCs (aDC; DCVax-Direct) for intratumoral injection in inoperable tumors for which limited treatment options exist. These aDC retain antigen uptake and presentation capability and are conditioned to complete the maturation process following injection, resulting in initiation of a broad anti-tumor immune response. Preclinical animal data have demonstrated that these aDC can mobilize both local and systemic immune responses, and effectively clear both injected (local) and non-injected (distal) inoperable tumor lesions. Methods: The Phase I component of the trial aims to enroll 6 patients each in following indications: colorectal cancer, lung cancer, breast cancer with brain metastases, pancreatic cancer, melanoma and ‘other’. Patients must have had at least one recent anti-tumor treatment other than active immune therapy prior to enrollment into the trial. A dose escalation across indications investigates the safety of 3 dose levels. The aDC are injected intratumorally, using imaging guidance, at days 0, 7 and 14, followed by injections at 8 and 16 weeks. Initial DLT assessments are done following the first three injections. Tumor biopsies are taken at the time of injections to assess local effects on the injection of aDC, and tumor response is assessed using both RECIST and Immune Related Response Criteria, starting 8 weeks after the first injection. The first dose cohort of the Phase I component has completed DLT assessments, and the second dose cohort’s enrollment is nearly complete. In addition, the “other” cohort of multiple cancers has been fully enrolled. Correlative immune-biomarkers studies to evaluate response and/or resistance mechanisms are planned. The Phase II component will enroll 24 patients in a selected indication, based on the results obtained in Phase I. Clinical trial information: NCT01882946.
Immunotherapy with Autologous Anti-CD19 Chimeric Antigen Receptor T Cells Followed By Allogeneic Hematopoietic Stem Cell Transplantation Has Remarkably Improved Leukemia-Free Survival in Refractory/Relapsed B-Cell Acute Lymphoblastic Leukemia
Authors: Yan-Li Zhao, Tong Wu, De-Yan Liu, Jian-Ping Zhang, Zhi-Jie Wei, Yue Lu, Xing-Yu Cao, Min Xiong, Jia-Rui Zhou, Rui-Juan Sun, Shu-Quan Ji, Chun-Rong Tong, Dao-Pei Lu
Journal: Blood (2016)
Challenges and opportunities in understanding dementia and delirium in the acute hospital
Authors: Thomas A. Jackson, John R. F. Gladman, Rowan H. Harwood, Alasdair M. J. MacLullich, Elizabeth L. Sampson, Bart Sheehan, Daniel H. J. Davis
Journal: PLoS Medicine (2017)

In an Essay, Andrew Jackson and colleagues discuss challenges in the diagnosis and management of older people with dementia and delirium in acute hospitals.
Dovitinib plus fulvestrant in postmenopausal endocrine resistant HER2-/ HR+ breast cancer: A phase II, randomized, placebo-controlled study.
Authors: Fabrice Andre, Patrick Neven, Antonino Musolino, Luciano Latini, Mario Campone, Javier Cortes, Carlos H. Barrios, Matthew Squires, Yong Zhang, Stephanie Deudon, Alejandro Javier Yovine, Kimberly L. Blackwell
Journal: Journal of Clinical Oncology (2013)

TPS651 Background: Overcoming endocrine resistance (ER) is a critical goal in the treatment of hormone receptor−positive (HR+) breast cancer (BC). Emerging in vitro evidence suggests that amplification and overexpression of fibroblast growth factor receptor 1 (FGFR1) is associated with ER. Up to 8% pts with HR+/ human epidermal growth factor receptor 2 negative (HER2–) BC have amplification of the FGFR1 gene. Dovitinib (DOV), a potent inhibitor of FGFR, vascular endothelial growth factor receptor, and platelet-derived growth factor receptor demonstrated antitumor activity in heavily pretreated BC pts with FGF-pathway amplification (FGFR1, FGFR2, or FGF3). The objective of this study is to determine if DOV plus fulvestrant (FUL) can improve outcomes in postmenopausal pts with endocrine resistant HER2-/HR+ BC. Methods: This multicenter, randomized, double-blind, placebo-controlled, ph II trial (NCT01528345) will enroll postmenopausal pts with HER2–/HR+ locally advanced or metastatic BC (N=150) progressing within 12 months of completion of adjuvant endocrine therapy or after ≤ 1 prior endocrine therapy in the advanced setting. Pts will be randomized 1:1 (stratified by FGF amplification and presence of visceral disease) to receive intramuscular FUL (500 mg q4w [with an additional dose 2 weeks after the initial dose]) plus oral DOV (500 mg, 5 days on/2 days off) or matching placebo until disease progression, unacceptable toxicity, death, or discontinuation (any reason). Crossover is not permitted. Primary endpoint is progression free survival (investigator’s assessment; RECIST v1.1). Secondary endpoints include overall response rate (investigator’s assessment; RECIST v1.1), duration of response, overall survival, time to deterioration of ECOG performance status, pt-reported outcome scores over time, safety, and assessment of plasma pharmacokinetic concentrations of FUL and DOV. Additionally, the pharmacodynamic effect of DOV on FGFR-associated angiogenic pathways in tumor specimens and potential predictive biomarkers of response to DOV will be explored. As of 21 Jan 2013, 128 pts had molecular screening; 73 pts are enrolled (of these 9 pts are FGF amplified). Clinical trial information: NCT01528345.
Phase I study of defactinib combined with pembrolizumab and gemcitabine in advanced cancer.
Authors: Andrea Wang-Gillam, Albert C. Lockhart, Benjamin R. Tan, Rama Suresh, Preet Paul Singh, Kian-Huat Lim, Katrina Pedersen, Manik A. Amin, William G. Hawkins, David G DeNardo
Journal: Journal of Clinical Oncology (2017)

TPS505 Background: Focal adhesion kinase (FAK) is consistently hyperactivated in pancreatic ductal adenocarcinoma (PDAC), and FAK signaling is a key driver in forming its fibrotic and proinflammatory tumor microenvironment. Inhibition of FAK signaling leads to significant reduction of pancreatic tumor growth in animal models. Indeed, tumors treated with FAK inhibitors displayed markedly reduced tumor fibrosis and decreased immunosuppressive myeloid cells. Furthermore, our preclinical work has demonstrated that FAK- and PD-1 inhibitors elicit significant tumor regression, and the maximal response was achieved by combining FAK- and PD-1 inhibitors with gemcitabine, suggesting the need for a cytotoxic agent to bolster antigen presentation (Jiang H et al, Nature Medicine 2016). Defactinib is an orally available, potent ATP-competitive, FAK inhibitor with a recommended phase II dose (RP2D) of 400 mg twice daily. Methods: Eligible patients will be treated according to the dose escalation schema. A 3+3 design is used until the first occurrence of dose-limiting toxicity, and then switches to a continuous assessment design. The study has an expansion portion (group A and B) at the RP2D. Group A includes metastatic PDAC patients who are stable at least 4 months on front-line nab-paclitaxel/gemcitabine, and group B includes metastatic PDAC patients progressed on ≥ 1 chemotherapy line. Key eligibility criteria include patients with advanced solid tumors (dose escalation portion) or advanced PDAC (expansion cohort); age ≥18 years; ECOG score ≤1; normal organ function; and no history autoimmunity. The primary endpoint is to determine the RP2D. Secondary endpoints include objective response rate, progression-free survival and overall survival. The exploratory endpoints include developing a molecular and immune signature for treatment response. This trial is actively enrolling and funded by Precision Medicine Research Associate and Barnes Jewish Foundation. Clinical trial information: NCT02546531. [Table: see text]
Sofosbuvir faces fresh patent challenge in Europe
Authors: Ned Stafford
Journal: BMJ (2017)

The medical aid charity Doctors Without Borders (Medecins Sans Frontieres) and other non-governmental organisations have begun a new legal challenge aimed at revoking the European patent for the blockbuster hepatitis C treatment sofosbuvir, to allow the sale in Europe of cheaper generic versions of the drug.

The patent is held by the US drug firm Gilead Sciences, which markets sofosbuvir under the highly profitable brand name Sovaldi. Sofosbuvir is also a component of Harvoni and Epclusa, two other hepatitis C treatments marketed in Europe by Gilead Sciences.

The new patent challenge, filed on 27 March 2017 at the European Patent Office in Munich, is the second major challenge to one of Gilead’s European patents for sofosbuvir. The first challenge was filed in 2015 by several groups, …
Direct access screening colonoscopy as a safe and effective approach to increasing colorectal cancer screening.
Authors: Joaquin J Estrada, Ana M Bedon, Jan P Kaminski, Gabriel Rodriguez, Mahmoud Ali, Andrew Albert
Journal: Journal of Clinical Oncology (2017)

540 Background: This year 135,000 patients will be diagnosed with colorectal cancer (CRC) and it is the second leading cause of cancer deaths in the US. CRC is largely preventable when screening is conducted. Nearly 60% of patients over 50 report never receiving any form of CRC screening. Colonoscopy remains the gold standard for CRC screening. Unfortunately, several barriers exist to obtaining this life-saving screening option (i.e. access to gastroenterologists, patient anxiety and lack of knowledge about the procedure). Our Direct Access Screening Colonoscopy program (DASC) has provided a successful solution to address many of these deterrents. Methods: In July 2015, the DASC program was launched at Advocate Illinois Masonic Medical Center. A nurse navigator telephonically completes health questionnaires and if patients were determined to be without significant comorbidities, they would be enrolled in the program. Prior to the procedure, the nurse would address all questions, instructions and bowel preparations. Patients that were not eligible for the program were navigated to a gastroenterologist for a formal evaluation. A retrospective review of all patients that underwent screening colonoscopy from July 2015 to July 2016 was conducted. Data collected included patient demographics, quality of preparation, Adenoma Detection Rate (ADR), patient satisfaction, and complications. Results: A total of 644 patients were referred for DASC. 373 patients (58%) were eligible for inclusion within the program. At the time of submission, 289 completed their colonoscopy. 201 patients (70%) had a normal colonoscopy. 88 patients were found to have at least one adenoma (ADR- 30%). No patients experienced any complications following DASC. Patient satisfaction scores were significantly higher for those who underwent DASC. The overall screening rate nearly doubled after implementation of the DASC program (30% vs 59%). Conclusions: Direct Access Screening Colonoscopy is a novel method to that increased the overall screening rate for CRC by almost 100%. It is a safe and effective alternative to the conventional process of obtaining a colonoscopy and can positively impact patient satisfaction and outcomes.
Inflammasome Activation Triggers Caspase-1-Mediated Cleavage of cGAS to Regulate Responses to DNA Virus Infection
Authors: Yutao Wang, Xiaohan Ning, Pengfei Gao, Shuxian Wu, Mengyin Sha, Mengze Lv, Xiang Zhou, Juyi Gao, Run Fang, Guangxun Meng, Xiaodong Su, Zhengfan Jiang
Journal: Immunity (2017)