tbuckley/cabot-search huggingface dataset:
Survival outcomes of hepatic resection compared with transarterial chemoembolization or sorafenib for hepatocellular carcinoma with portal vein tumor thrombosis
Authors: Jung Min Lee, Byoung Kuk Jang, Yoo Jin Lee, Wang Yong Choi, Sei Myong Choi, Woo Jin Chung, Jae Seok Hwang, Koo Jeong Kang, Young Hwan Kim, Anil Kumar Chauhan, Soo Young Park, Won Young Tak, Young Oh Kweon, Byung Seok Kim, Chang Hyeong Lee
Journal: Clinical and Molecular Hepatology (2016)

Background/Aims: Treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remains controversial. We compared the outcomes of hepatic resection (HR), transarterial chemoembolization (TACE), and sorafenib therapy as treatments for HCC with PVTT. Methods: Patients diagnosed as HCC with PVTT between January 2000 and December 2011 who received treatment with sorafenib, HR, or TACE were included. Patients with main PVTT, superior mesenteric vein tumor thrombosis, or Child-Turcotte-Pugh (CTP) class C were excluded. The records of 172 patients were analyzed retrospectively. HR, TACE, and sorafenib treatment were performed is 40, 80, and 52 patients respectively. PVTT was classified as either involving the segmental branch (type I) or extending to involve the right or left portal vein (type II). Results: The median survival time was significantly longer in the HR group (19.9 months) than in the TACE and sorafenib groups (6.6 and 6.2 months, respectively; both p<0.001), and did not differ significantly between the latter two groups (p=0.698). Among patients with CTP class A, type I PVTT or unilobar-involved HCC, the median survival time was longer in the HR group than in the TACE and sorafenib groups (p=0.006). In univariate analyses, the initial treatment method, tumor size, PVTT type, involved lobe, CTP class, and presence of cirrhosis or ascites were correlated with overall survival. The significant prognostic factors for overall survival in Cox proportional-hazards regression analysis were initial treatment method (HR vs. TACE: hazard ratio=1.750, p=0.036; HR vs. sorafenib: hazard ratio=2.262, p=0.006), involved lobe (hazard ratio=1.705, p=0.008), PVTT type (hazard ratio=1.617, p=0.013), and CTP class (hazard ratio=1.712, p=0.012). Conclusions: Compared with TACE or sorafenib, HR may prolong the survival of patients with HCC in cases of CTP class A, type I PVTT or unilobar-involved HCC. Keywords: Hepatocellular carcinoma; Portal vein tumor thrombosis; Transarterial chemoembolization; Hepatic resection; Sorafenib
Multiple Myeloma: Advances Reported in 2013 Are Useful in the Clinic
Authors: Kenneth Anderson
Journal: Journal of the National Comprehensive Cancer Network (2014)

Studies on multiple myeloma reported in 2013 offer support for maintenance after induction and consolidation in newly diagnosed patients eligible for transplantation and for continued lenalidomide in patients not eligible for transplantation. The newest available agents, carfilzomib and pomalidomide, are approved to treat relapsed/refractory myeloma, and in combination they produce impressive response rates and durability. On the horizon, new classes of agents promise even more impressive gains in remission and survival.
Abstract 5115: An orthotopic lung tumor model for image-guided microirradiation in rats
Authors: Zhang Zhang, Michelle Wodzak, Olivier Belzile, Heling Zhou, Ralph Mason, Rolf Brekken, Rajiv Chopra, Michael D. Story, Robert Timmerman, Debabrata Saha
Journal: Cancer Research (2015)

Abstract Introduction: Studies have confirmed that a new lung cancer treatment called stereotactic body radiation therapy (SBRT) can cure certain patients with early stage tumors situated peripherally in their lungs, using a non-invasive, outpatient procedure. While nearly curative for peripheral lung tumors, SBRT also may present life-threatening toxicity for patients with centrally located lung tumors. Moreover, large, hypoxic tumors are at a further risk of radiotherapy failure with SBRT. The efficacy of SBRT application can be improved through the addition of agents designed to sensitize the tumor and/or protect normal tissue. To investigate and validate the response to SBRT, alone or in combination with radiomodulating compounds, it is necessary to develop a tumor model for image-guided high-dose irradiation of rodent tumors and normal tissues in a manner that closely mimics delivery of SBRT in humans. Therefore, the purpose of this study was to develop a rat orthotopic lung tumor model with a solitary intrapulmonary nodule to study the effects of high-dose radiation. Methods: Adult female athymic nude rats were anesthetized, intubated and then placed on a ventilator (Inspira, Harvard Apparatus, Holliston, MA) prior to surgery. A small incision (1.0 cm) was made between ribs 5 and 6 on the right side. The right lung was captured using a forceps, clamped with a carotid clamp and H460-luc/A549-luc NSCLC cells (one million cells and matrigel in 20 μl) were then injected into the right lung. The tumor growth was monitored by in vivo bioluminescent imaging (BLI) weekly. Other imaging modalities, including microCT, CBCT, and MRI, were also performed. At the end of study, the rats were sacrificed and lungs were harvested to confirm tumor location and size. Results: We achieved 100% survival from this surgical orthotopic implantation procedure. We also achieved &amp;gt;90% success in generating solitary lung tumors in the rats, whereas percutaneous orthotopic injection of tumor cells/chunks in our previous model met only 50 to 60% success in producing solitary tumors. Conclusion: This study presents a successful solitary lung tumor model in rodents which provides investigators a useful model to apply conformal radiation treatment, using a sophisticated treatment planning system and significantly preventing normal tissue damage. Citation Format: Zhang Zhang, Michelle Wodzak, Olivier Belzile, Heling Zhou, Ralph Mason, Rolf Brekken, Rajiv Chopra, Michael D. Story, Robert Timmerman, Debabrata Saha. An orthotopic lung tumor model for image-guided microirradiation in rats. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5115. doi:10.1158/1538-7445.AM2015-5115
A Method for Using Life Tables to Estimate Lifetime Risk for Prostate Cancer Death
Authors: Hyung L. Kim, Marvin R. Puymon, Maochun Qin, Khurshid Guru, James L. Mohler
Journal: Journal of the National Comprehensive Cancer Network (2010)

Prostate cancer can have a long and indolent course, and management without curative therapy should be considered in select patients. When counseling patients, a useful way to convey the risk for death from competing causes is to estimate their lifetime risk for dying from prostate cancer. Double-decrement life tables were constructed to calculate age-specific death rates using the death probabilities from the Social Security Administration life tables and Gleason score-specific mortality rates reported from a pre-PSA cohort study. The lifetime risk for prostate cancer death was calculated. Life tables provided life expectancy and risk for prostate cancer death based on age at diagnosis. For example, a 60-year-old patient with a Gleason score 6, 7, or 8 tumor had an overall life expectancy of 14.4, 10.2, or 6.6 years, respectively. The risk for prostate cancer death during the expected years of life was 33%, 49%, or 57%, respectively. If a 10-year lead-time bias was assumed for PSA detection, the risks for death from prostate cancer decreased to 16%, 26%, or 37%, respectively. If the patient was in the bottom quartile for overall health and disease was detected by prostate examination, the risk for death from prostate cancer was 21%, 32%, or 40%, respectively. A Web-based tool for performing these calculations is available at http://www.roswellpark.org/Patient_Care/Specialized_Services/Prostate_Cancer_Estimator.html. Life tables can be created to estimate overall life expectancy and risk for prostate cancer death, and to assist with decision-making when considering management without curative therapy.
A Case of Unusual Mast Cell Response With Interstitial Cystitis-Like Symptoms to Neoadjuvant Chemotherapy for Muscle-Invasive Transitional Cell Carcinoma of the Bladder
Authors: Venkata Pokuri, Norbert Sule, Yousef Soofi, Bo Xu, Khurshid Guru, Saby George
Journal: Journal of the National Comprehensive Cancer Network (2013)

Randomized trials support the use of neoadjuvant chemotherapy in muscle-invasive bladder cancer based on a noted survival advantage, which appeared to be strongly related to downstaging of the cancer to pT0 (complete pathologic response). This report presents a case of an unusual mast cell response along with bladder wall thickening after neoadjuvant chemotherapy. However, the final cystectomy specimen did not reveal any residual tumor (pT0). The authors hypothesize that neoadjuvant chemotherapy could have caused the diffuse mast cell response, and that this profound inflammatory response can be used as a biomarker of complete response to chemotherapy.
Measurements, composite scores and the art of ‘cutting-off’
Authors: Pedro M Machado
Journal: Annals of the Rheumatic Diseases (2016)

Measuring is an essential part of medicine, both in research as well as in clinical practice. Clinical reasoning itself is a mental exercise based on a succession of tests and assessments (signs and symptoms and their quantification, impact on the patient, findings from the physical examination, results from laboratory and imaging investigations, among others) that result in making a diagnosis and making therapeutic decisions.1 Lord Kelvin’s (1824–1907) quote from 1883 extracted from a lecture on ‘Electrical Units of Measurement’ also applies to modern medicine: ‘When you can measure what you are speaking about, and express it in numbers, you know something about it; but when you cannot measure it, when you cannot express it in numbers, your knowledge is of a meagre and unsatisfactory kind; it may be the beginning of knowledge, but you have scarcely, in your thoughts, advanced to the stage of science, whatever the matter may be’.

The use of general or disease-specific measuring tools has become routine in rheumatology. In addition to the critical need of these tools for drug development, they are also valuable for patient management. These tools vary from simple visual analogue scales or numerical rating scales, for example, for pain or global assessment of disease activity, to patient-reported outcomes based on multiple questions, such as the Health Assessment Questionnaire (HAQ) or the Bath Ankylosing Spondylitis Functional Index, to composite indices such as the 28-joint count Disease Activity Score (DAS28) and the Ankylosing Spondylitis Disease Activity Score, which combine patient-reported and/or physician-reported variables with the laboratory measurement of acute phase reactants (C reactive protein (CRP) or erythrocyte sedimentation rate). Composite measures can be particularly helpful and are more likely to give more complete and reliable information about a certain health outcome such as disease activity.

Cut-offs increase the interpretability of a measurement …
A systematic review and meta-analysis of low intensity CBT for psychosis
Authors: Cassie M. Hazell, Mark Hayward, Kate Cavanagh, Clara Strauss
Journal: Clinical Psychology Review (2016)

Sixteen sessions of individual cognitive behavior therapy for people with psychosis (CBTp) is recommended. However, access to CBTp is poor, so the potential of low intensity CBTp (fewer than 16 sessions of face-to-face contact) is being explored. A systematic review and meta-analysis was conducted of 10 controlled trials evaluating low intensity CBTp. Significant between-group effects were found on the primary outcome, symptoms of psychosis, at post-intervention (d=-0.46, 95% CI: -0.06, -0.86) and follow-up (d=-0.40, 95% CI: -0.06, -0.74). Study quality did not moderate post-intervention psychosis outcomes, nor did contact time/number of sessions or therapy format (individual versus group). Between-group effects on secondary outcomes (depression, anxiety and functioning) were not significant at post-intervention, but became significant at follow-up for depression and functioning outcomes (but not for anxiety). Overall, findings suggest that low intensity CBTp shows promise with effect sizes comparable to those found in meta-analyses of CBTp more broadly. We suggest that low intensity CBTp could help widen access. Future research is called for to identify mechanisms of change and to ascertain moderators of outcome so that low intensity CBTp targets key mechanisms (so that scarce therapy time is used effectively) and so that interventions offered are matched to patient need.
Antitumor activity and safety of pembrolizumab in patients (pts) with advanced squamous cell carcinoma of the head and neck (SCCHN): Preliminary results from KEYNOTE-012 expansion cohort.
Authors: Tanguy Y. Seiwert, Robert I. Haddad, Shilpa Gupta, Ranee Mehra, Makoto Tahara, Raanan Berger, Se-Hoon Lee, Barbara Burtness, Dung T. Le, Karl Heath, Amy Blum, Marisa Dolled-Filhart, Kenneth Emancipator, Kumudu Pathiraja, Jonathan D. Cheng, Laura Q. Chow
Journal: Journal of Clinical Oncology (2015)

LBA6008 Background: Pembrolizumab (MK-3475) is a humanized monoclonal antibody that blocks interaction of PD-1 with its ligands, PD-L1 and PD-L2, thereby promoting activity of tumor-specific effector T cells. KEYNOTE 012 (NCT01848834) had previously demonstrated clinical activity of pembrolizumab 10 mg/kg every 2 weeks in patients (pts) with recurrent/metastatic SCCHN enriched for PD-L1–positive tumors with a response rate of 20%. We now report on the larger SCCHN expansion cohort of KEYNOTE 012, irrespective of biomarker status using a 3-weekly fixed dose. Methods: Pts with advanced SCCHN irrespective of PD-L1 expression or HPV status received a fixed dose of 200 mg pembrolizumab, intravenously, every 3 weeks. Pts were evaluated every 8 weeks with radiographic imaging. The primary end point was overall response rate (ORR) per investigator assessment (RECIST 1.1). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were assessed according to CTCAE v4. PD-L1 was assessed retrospectively by immunohistochemistry. Results: 132 pts with recurrent/metastatic SCCHN were enrolled. Mean (SD) age was 58.9 (9.7) years; 83.3% were male; 56.8% had ≥ 2 lines of therapy for recurrent disease. 73/132 pts (55.3%) remain on treatment. Out of 132 treated pts, 99 pts were available for this preliminary efficacy analysis with a post-baseline scan or discontinued therapy prior to the scan due to clinical progression or AE. ORR (confirmed and unconfirmed) per RECIST 1.1 was 18.2% (95% CI, 11.1-27.2) with 18 partial responses and 31.3% with stable disease. Biomarker analysis is ongoing and results will be presented. Drug-related AEs of any grade occurred in 47% of all enrolled pts, and drug-related grade ≥ 3 AEs occurred in 7.6%. The most common drug-related AEs ( ≥ 5%) of any grade were fatigue (12.1%), decreased appetite (6.8%), pyrexia (6.1%), and rash (5.3%). Conclusions: Pembrolizumab given at a fixed dose of 200 mg every 3 weeks was well tolerated and demonstrated a clinically meaningful ORR of 18.2% in pts with recurrent/metastatic SCCHN. Clinical trial information: NCT01848834.
Therapeutic In Vivo Photochemistry: Photochemical Toxicity Studies in Humans&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Parrish, John A.
Journal: JNCI Journal of the National Cancer Institute (1982)

Therapeutic In Vivo Photochemistry: Photochemical Toxicity Studies in Humans Get access John A. Parrish, M.D. John A. Parrish, M.D. 3Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, Boston, Mass. 02114. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 69, Issue 1, July 1982, Pages 273–278, https://doi.org/10.1093/jnci/69.1.273 Published: 01 July 1982
Phase I trial of a PSMA DNA vaccine for patients(pts) with good risk renal cell carcinoma(RCC)
Authors: S. F. Slovin, R. J. Motzer, M. Jefferson, P. Gregor, J. D. Wolchok, M. Czarny, T. Curley, A. Delacruz, H. I. Scher
Journal: Journal of Clinical Oncology (2008)

16073 Background: Prostate Specific Membrane Antigen (PSMA) is a self antigen first identified as a marker for epithelial cells in the prostate but is expressed on the vascular endothelium of metastatic RCC. PSMA mRNA transcripts and protein expression have been seen in the endothelium of tumor-associated neovasculature of non-metastatic malignancies. No PSMA mRNA or protein expression has been found in vascular endothelial cells of corresponding benign tissues. The clinical importance of PSMA expression is supported by the observation that PSMA RNA detected by RT-PCR in the circulation of RCC pts correlates with disease progression. A phase I trial was designed using a xenogeneic murine versus human PSMA DNA vaccine to evaluate safety in pts with RCC. Eighteen pts with clear cell RCC status post nephrectomy, cytokine therapy, or post metastastectomy with high risk of recurrent disease were enrolled. Good risk pts were defined as having a KPS of >80%, prior nephrectomy, normal calcium and hemoglobin levels. Methods: Six pts each were assigned to dose levels (500, 1500 and 3000μg) and were randomized to receive 3 murine or 3 human PSMA DNA vaccines im every 3 weeks. After the third vaccine, pts were crossed-over to the other species for an additional 3 vaccines. If pts remained disease-free or had clinically responding disease, booster immunizations were administered bimonthly for up to 4 additional booster vaccinations at weeks 24, 32, 40 and 48. Results: Ten of 15 treated pts were evaluable. The vaccine was well-tolerated. One pt from the 500μg dose level who received the murine vaccine first, and 2 pts from the 1500μg dose and 1 pt from the 3000μg dose who received the human PSMA DNA vaccine first, remain on study at 167, 114, 125 and 68 weeks, respectively. FACS analysis of pts’ sera against 3T3 fibroblasts genetically transduced to secrete PSMA showed no reactivity at the 500μg dose level; 1 of 2 pts at 1500μg and 1 pt at the 3000μg dose showed reactivity against PSMA, respectively. Minimal activity was seen by ELISA. Conclusions: The vaccine was safe at all dose levels without autoimmunity. The 2 pts at the 1500μg dose level have stable lung lesions. Studies are ongoing to examine other parameters of immune responsiveness. Supported by the Byrne Foundation No significant financial relationships to disclose.
Toxicity and health-related quality of life (HRQoL) in node-negative breast cancer (BC) patients (pts) receiving adjuvant treatment with TAC (docetaxel, doxorubicin, cyclophosphamide) or FAC (5-fluorouracil, doxorubicin, cyclophosphamide): Impact of adding prophylactic growth factors (GF) to TAC. GEICAM Study 9805
Authors: M. Martin, A. Lluch, M. Á. Seguí, A. Antón, C. Fernández-Chacón, A. Ruíz, M. Ramos, E. Adrover, Á. Rodríguez-Lescure, A. Casado
Journal: Journal of Clinical Oncology (2005)

604 Background: Node-positive BC pts treated with TAC have a longer disease-free and overall survival but a higher rate of febrile neutropenia (FN) compared with pts treated with FAC. We evaluated the toxicity and HRQoL of both regimens and assessed the impact of adding prophylactic granulocyte GF to TAC.Methods: 1059 pts with operable, high-risk (St Gallen, 1998), node-negative BC, 18–70 yrs old, were randomized to FAC (F 500 mg/m2, A 50 mg/m2, C 500 mg/m2) or TAC (T 75 mg/m2, A 50 mg/m2, C 500 mg/m2) day 1 every 3wks for 6 cycles. After enrolling 224 pts, the study was amended to require prophylactic GF for pts subsequently treated with TAC, but not FAC. The EORTC QLQ-C30 was administered at baseline, after each chemotherapy cycle and 6, 12 and 24 months after completion of chemotherapy. Rates of FN (fever ≥gr 2 with gr 4 neutropenia), severe asthenia, gr 3–4 diarrhea, and gr 2–4 mucositis were analyzed. Results: 530 pts received TAC, 114 without GF [TAC] and 416 with GF [TAC+G]; 520 received FAC. During chemotherapy, HRQoL was worse with TAC than with FAC (p=0.008), with a maximum difference of 8.0 points during cycle 4. However, no statistically significant differences in HRQoL were observed between TAC+G and FAC, with 6.1 points as the highest difference during cycle 3. During the follow-up period, no statistically significant differences in HRQoL were observed among TAC alone, TAC+G and FAC. The incidence[95%CI] of: FN was 2.3%[1.0–3.6%] for FAC, 24.6%[16.7–32.5%] for TAC, and 5.8%[3.53–8.01%] for TAC+G; gr 3–4 diarrhea 0.8% FAC, 7.0% TAC, and 2.6% TAC+G (p=0.0415); severe asthenia 1.8% FAC, 20.2% TAC, and 5.5% TAC+G (p<0.0001); gr 2–4 mucositis 24.4% FAC, 35.1% TAC, and 23.3% TAC+G (p=0.011). Conclusions: TAC transiently worsens HRQoL compared with FAC during chemotherapy. However, BC pts treated with TAC plus GF support experience the same HRQoL as pts treated with FAC. The addition of GF to TAC significantly reduces the incidence of FN, gr 3–4 diarrhea, severe asthenia, and gr 2–4 mucositis compared with TAC alone. No significant financial relationships to disclose.
miR-223–IGF-IR signalling in hypoxia- and load-induced right-ventricular failure: a novel therapeutic approach
Authors: Lei Shi, Baktybek Kojonazarov, Amro Elgheznawy, Rüdiger Popp, Bhola Kumar Dahal, Mario Böhm, Soni Savai Pullamsetti, Hossein-Ardeschir Ghofrani, Axel Gödecke, Andreas Jungmann, Hugo A. Katus, Oliver J. Müller, Ralph T. Schermuly, Beate Fisslthaler, Werner Seeger, Ingrid Fleming
Journal: Cardiovascular Research (2016)

Pulmonary hypertension is a progressive disease with poor prognosis, characterized by pathological inward remodelling and loss of patency of the lung vasculature. The right ventricle is co-affected by pulmonary hypertension, which triggers events such as hypoxia and/or increased mechanical load. Initially the right ventricle responds with 'adaptive' hypertrophy, which is often rapidly followed by 'maladaptive' changes leading to right heart decompensation and failure, which is the ultimate cause of death. We report here that miR-223 is expressed in the murine lung and right ventricle at higher levels than in the left ventricle. Moreover, lung and right-ventricular miR-223 levels were markedly down-regulated by hypoxia. Correspondingly, increasing right-ventricular load by pulmonary artery banding, induced right-ventricular ischaemia, and the down-regulation of miR-223. Lung and right ventricle miR-223 down-regulation were linked with increased expression of the miR-223 target; insulin-like growth factor-I receptor (IGF-IR) and IGF-I downstream signalling. Similarly, miR-223 was decreased and IGF-IR increased in human pulmonary hypertension. Notably in young mice, miR-223 overexpression, the genetic inactivation or pharmacological inhibition of IGF-IR, all attenuated right-ventricular hypertrophy and improved right heart function under conditions of hypoxia or increased afterload. These findings highlight the early role of pulmonary and right-ventricular miR-223 and the IGF-IR in the right heart failure programme initiated by pulmonary hypoxia and increased mechanical load and may lead to the development of novel therapeutic strategies that target the development of PH and right heart failure.
An intervention to reduce the rate of hospital discharges against medical advice
Authors: S D Targum, A E Capodanno, H A Hoffman, C Foudraine
Journal: American Journal of Psychiatry (1982)

The initiation of a patient advocacy program in a private psychiatric hospital in 1980 was effective in significantly reducing the rate of hospital discharges against medical advice relative to the rate in 1979 and in 1978. There was also a concomitant increase in the rate of clinically approved discharges relative to that in 1979 and in 1978. The authors view the patient advocate as an objective intermediary who represents an acknowledgment of patients' rights and affords patients an opportunity to have some autonomy and an impact on the hospital system.