tbuckley/cabot-search huggingface dataset:
Analysis of long-term treatment outcomes and toxicty of HL
Authors: J. Y. Ngeow, R. Quek, M. Tao, H. C. Tan, L. Lim, I. Tan, R. Kaneswaran, S. T. Lim
Journal: Journal of Clinical Oncology (2009)

e19536 Background: Prognosis of patients with Hodgkin lymphoma (HL) has substantially improved but therapy of HL can however contribute to delayed toxicity. Long term treatment outcomes of HL in our local population were evaluated. Methods: Clinical and treatment data was prospectively collected from all patients with a histological diagnosis of HL. Patients were all fully staged with CT scan and bone marrow biopsy. Results: On the basis of 217 patients seen at the National Cancer Centre Singapore between 1990–2008, we found that there was a peak in young adulthood with 103 patients who were diagnosed before the age of 30 (48%), median age of presentation 32 (range 17–84). Patients who were young (&lt; 30 years) were more likely to present with nodular sclerosis HL (p=0.0001). Treatment outcomes were comparable to other published series, 85% of cases received ABVD based treatment. 5 year OS for early stage HL was 92% and 88% for advanced stage HL. Overall FFTF was 93% at 5 years. Of note, comparing patients with early stage (Stage I/ II) HL (n=114) who had ABVD 4 cycles followed by involved field radiotherapy (IFRT) with those who received 6–8 cycles of ABVD, there was no difference in OS, FFTF (p= 0.99, 0.48 respectively). Bulky early stage HL who received 6 cycles of ABVD and IFRT had better FFTF rates than those who had just 4 cycles of ABVD followed by IFRT (p=0.06). In contrast, patients patients with advanced HL (Stage III/ IV) (n=70) who completed 6–8 cycles of ABVD did not benefit from additional IFRT even in the presence of bulky disease (n=15). Acute toxicities included that of bleomycin induced pneumonitis (BIP) seen in 15% of cases. Neither the omission of bleomycin nor the presence BIP adversely affected treatment outcomes. Hematological malignancies were seen in 1% of survivors appearing after a median of 7.3 years. Hypothyroidism was noted in 3% of cases. Conclusions: 1) Epidemiology of HL in Singapore is increasingly similar to that of developed countries with a peak in young adults. 2)Young age was predictive of a nodular sclerosis subtype 3) Abbreviated chemotherapy using 4 cycles of ABVD followed by IFRT performed similarly to 6 cycles of ABVD in early stage HL, but in patients with bulky disease this may not be sufficient. 4) BIP occurred in 15% of cases. BIP and the omission of bleomycin did not adversely affect treatment outcomes. No significant financial relationships to disclose.
Pancreatic Cancer: Challenge and Inspiration
Authors: Susan E. Bates
Journal: Clinical Cancer Research (2017)

The recent enthusiasm over new discoveries in cancer immunotherapy has made it painfully evident how difficult progress in the therapy of pancreatic cancer has been and how very difficult it remains. If you are lucky (25% of those diagnosed), you are able to undergo curative resection to then recover and sustain 6 months of adjuvant chemotherapy followed by intensive surveillance to detect a likely recurrence (median survival of 28 months in the most recent ESPAC-4 study). If unlucky, and the disease is metastatic, median survivals have yet to exceed 12 months. To date, all preclinical insights have met an unforgiving reality test when they arrived in the clinic. Indeed, several meta-analyses have shown the difficulty of improving over gemcitabine monotherapy; almost 14,000 patients across 47 trials invested in developing current best therapies (1–5). These numbers from investigators around the world are a testament to the efforts expended. We can argue that the majority of these studies have tried to make incremental changes, usually by adding an existing agent with supporting data that all too often was at best modest. But we can also argue that at present, our knowledge about pancreatic cancer is rapidly expanding, and novel insights may yet bring a change. In this spirit, this CCR Focus aims to highlight new discoveries in pancreatic cancer genetics, including the foundational mutational signatures at the DNA level, bring new understanding to the tumor microenvironment and how normal components of pancreatic inflammatory response have been appropriated to maintain the malignant phenotype, investigate the failure of immunotherapy in pancreatic cancer to date and propose strategies to bring the immune system to bear in therapy, and outline novel approaches ongoing in the clinic. Guest Editors Dan Von Hoff and John Chabot and I have assembled a group of experts in the field to frame these discoveries and insights. As with every issue of CCR Focus, the goal is to inform the interested nonexpert and to encourage and stimulate the experts working in the field, and thus contribute to the search for new therapies for our patients.Susan E. BatesDeputy Editor, CCR FocusColumbia University Medical CenterSee all articles in this CCR Focus section, “Pancreatic Cancer: Challenge and Inspiration.”
Response by Sörensen et al to Letters Regarding Article, “Prediabetes and Type 2 Diabetes Are Associated With Generalized Microvascular Dysfunction: The Maastricht Study”
Authors: Ben M. Sörensen, Alfons J.H.M. Houben, Remy J.H. Martens, Coen D.A. Stehouwer
Journal: Circulation (2017)
Risk factors for MERS coronavirus infection in dromedary camels in Burkina Faso, Ethiopia, and Morocco, 2015
Authors: Eve Miguel, Véronique Chevalier, Gelagay Ayelet, M.Nadji Bencheikh, Hiver Boussini, Daniel Ka Chu, Ikhlass El Berbri, Ouaffa Fassi-Fihri, Bernard Faye, Getnet Fekadu, Vladimir Grosbois, Boon C. Ng, Rushika Perera, Timothy Y. C So, Adama Traore, Françoise Roger, Malik Peiris
Journal: Eurosurveillance (2017)

Understanding Middle East respiratory syndrome coronavirus (MERS-CoV) transmission in dromedary camels is important, as they consitute a source of zoonotic infection to humans. To identify risk factors for MERS-CoV infection in camels bred in diverse conditions in Burkina Faso, Ethiopia and Morocco, blood samples and nasal swabs were sampled in February–March 2015. A relatively high MERS-CoV RNA rate was detected in Ethiopia (up to 15.7%; 95% confidence interval (CI): 8.2–28.0), followed by Burkina Faso (up to 12.2%; 95% CI: 7–20.4) and Morocco (up to 7.6%; 95% CI: 1.9–26.1). The RNA detection rate was higher in camels bred for milk or meat than in camels for transport (p = 0.01) as well as in younger camels (p = 0.06). High seropositivity rates (up to 100%; 95% CI: 100–100 and 99.4%; 95% CI: 95.4–99.9) were found in Morocco and Ethiopia, followed by Burkina Faso (up to 84.6%; 95% CI: 77.2–89.9). Seropositivity rates were higher in large/medium herds (≥51 camels) than small herds (p = 0.061), in camels raised for meat or milk than for transport (p = 0.01), and in nomadic or sedentary herds than in herds with a mix of these lifestyles (p &lt; 0.005).
The great NHS debate
Authors: Elizabeth Loder
Journal: BMJ (2017)

In recent days The BMJ has been filled with commentary and debate about the future of the NHS. NHS England’s updated delivery plan calls for many changes in the way healthcare is provided and the priority attached to specific services. Without extra money, this is a zero sum game. More resources devoted to integrated care, extended hours for GPs, and improved mental health and cancer services mean fewer resources for other things. For example, the 18 week waiting time target for elective surgery has been abandoned (doi:10.1136/bmj.j1652).

A House of Lords inquiry into NHS sustainability concludes that a plan of …
Lingering Questions Concerning Specific Dietary Fats and Mortality—Reply
Authors: Dong D. Wang, Walter C. Willett, Frank B. Hu
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Omalizumab is effective in symptomatic dermographism—results of a randomized placebo-controlled trial
Authors: Marcus Maurer, Andrea Schütz, Karsten Weller, Nicole Schoepke, Adriane Peveling-Oberhag, Petra Staubach, Sabine Müller, Thilo Jakob, Martin Metz
Journal: Journal of Allergy and Clinical Immunology (2017)
Analysis of over 2,400 modern phase I cancer trials: Composition, outcomes, and use of surrogate endpoints
Authors: T. G. Roberts, B. H. L. Goulart, S. C. Stallings, L. Squitieri, B. A. Chabner, S. N. Finkelstein, J. W. Clark
Journal: Journal of Clinical Oncology (2004)

2084 Background: There has been no comprehensive analysis of phase I cancer trials since 1991, despite the transition from cytotoxic to targeted drugs. Trends in response rates (RR) and toxic death rates (TDR) for modern phase I trials are therefore unknown. We set out to perform the most extensive outcomes analysis to date of phase I cancer trials. Methods: We analyzed the composition and outcomes of all phase I cancer trials submitted to ASCO for years 1991 through 2002. For trials testing unapproved, single-agents in solid tumors, we reviewed published reports and performed patient-level analysis. The major outcomes variables included overall response rate (RR) and toxic death rate (TDR). Because of changes in phase I trial design, we also analyzed the use of biomarkers (BM) and surrogate endpoints (SE). Results: The overall data set included 2,439 trials. Composition and outcomes varied by year of submission to ASCO (Table). Over the period of analysis, phase I trials have become significantly more international, more complex in design, and more likely to identify a commercial sponsor. Drugs under investigation have become more likely to be given by the oral route, less likely to be produced by recombinant technology, and less likely to be cytotoxic. The strongest predictor for inclusion of a BM or SE was NIH sponsorship (odds ratio: 2.9). The overall RR and TDR for single-agent studies published in final form was 3.96% and 0.6%, respectively. Both RR and TDR fell significantly over the period. In linear regression models, RR fell from 8.0% in 1991 to 2.4% in 2001; but the fall in TDR was more pronounced over the same period. Significantly higher RRs and TDRs were seen among cytotoxic drugs as compared to targeted and biologic agents. Conclusions: The composition of phase I cancer trials submitted to ASCO is changing. Although overall RRs have declined, the risk/benefit ratio for patients may be improving. No significant financial relationships to disclose.
Predictors of significant emotional distress in cervical cancer patients.
Authors: Kathryn Osann, Susie Hsieh, Edward L. Nelson, David Cella, Lari B. Wenzel
Journal: Journal of Clinical Oncology (2013)

6632 Background: Cervical cancer patients experience serious quality of life (QOL) disruptions, which may include persistent emotional distress. Predictors of persistent or significant depression and anxiety are examined in this study. Methods: A randomized trial tested the efficacy of a psychosocial telephone counseling intervention designed to improve QOL and decrease emotional distress.The FACT-Cx Trial Outcome Index (FACT-Cx-TOI), depression and anxiety (PROMIS short forms) were collected at baseline (T1), 4 months (T2) and 9 months (T3) post enrollment. Multivariate linear and logistic regression models were used to identify predictors of distress at follow-up. Tested predictors included demographic information, stage, treatment assignment, and baseline FACT-Cx TOI and PROMIS scores. Results: 115 women were randomized to PTC and 89 to usual care, with 82% compliance for T2 and 75% at T3. PTC patients experienced a significantly greater reduction in depression from T1 to T2 compared to UC (p=0.014). At baseline, 45% of participants reported depression T-scores above 55 (0.5 SD above the US general population average), and 26% reported levels greater than 60 (&gt;1 SD worse than average). PTC patients were significantly less likely to have depression scores &gt;55 at T2, and significantly more likely to improve by ≥5 points at T2 after adjusting for baseline and disease characteristics. Participation in PTC, higher baseline depression and higher baseline TOI were significant independent predictors of improvement in depression from T1 to T2. Conclusions: Early identification of patients with poor QOL and significant depression can inform supportive care interventions, with potential to improve health outcomes. Funding Source: NCI R01 CA118136-01. Clinical trial information: NCT00496106.
The Drug Repurposing Hub: a next-generation drug library and information resource
Authors: Steven M Corsello, Joshua A Bittker, Zihan Liu, Joshua Gould, Patrick McCarren, Jodi E Hirschman, Stephen E Johnston, Anita Vrcic, Bang Wong, Mariya Khan, Jacob Asiedu, Rajiv Narayan, Christopher C Mader, Aravind Subramanian, Todd R Golub
Journal: Nature Medicine (2017)
Use of the word “death” in cancer care.
Authors: Amitoj Singh Gill, Shruti Bhandari, Rahul Gosain, Joseph Abraham, Stefan Terwindt, Robert Paul Stephan, Kenneth David Miller
Journal: Journal of Clinical Oncology (2014)

e20510 Background: Anecdotally, some medical oncologists are hesitant to use the words “Death” or “Dying” in talking to patients with advanced cancer. Patients report that dying may not be discussed with their doctor until death is imminent. The purpose of this pilot study was to evaluate oncologists’ use of the word “Death” in cancer care, what other words they use in referring to death, and when in a patient’s clinical course these discussions occur. Methods: A survey, designed in collaboration with MDoutlook, was emailed to a group of medical oncologists. Questions included demographics, medical training, and practice setting. Participants were asked to describe their use of the word “death”, other terminology they prefer, and the timing of these discussions. Results: Of the 93 medical oncologists that responded, 61% were male and 39% female, with a median of 24 years of practice post-training (Range: 2-49). Approximately 27% of oncologists used the terms “Death” or “Dying” either “all the time” or ”very often”, 36% used it ”often” and 37% used it “infrequently” or ”never”. Use of the terms “Death” or “Dying” was more common among male oncologists as compared to female oncologists (p=0.01) but was not significantly associated with age (p=0.6) and years of practice(p=0.3). When asked more specifically about patients with a prognosis of less than 1 year, 45% of oncologists report that they talk about death or dying during a first visit, 24% discuss death during the first month of care, 20% talk about death after a patient’s initial response to treatment and only 5% in the last month of life. Other words used by these oncologists to tell patients about death are, “I think the time is limited” (23.3%), “It is time to consider transitioning to hospice“ (20%), “You're recent scans show that the cancer is getting worse“ (15.5%), “You're disease has progressed“(11%). Among this group of oncologists, 60% report that patient ask, “How long will I live?” very often or all the time. Conclusions: End of life discussions can be difficult for both oncologists and patients. Over one third of oncologists surveyed use the specific words “Death” or ”Dying” either infrequently or never. Euphemisms are frequently used which may not optimally help patients and families make end of life decisions.
Phase I clinical trial of imexon: A mitochondrial thiol oxidant
Authors: R. T. Dorr, T. Dragovich, E. Hersh, K. Patrick
Journal: Journal of Clinical Oncology (2004)

3181 Background: Imexon is a thiol-binding small molecule which induces mitochondrial oxidation, a loss of membrane potential and cytochrome C, leading to apoptosis (Blood 97: 3544–50, 2001). In rodents and dogs the drug is schedule dependent favoring daily dosing with an MTD of 450mg/M2/day. Previous phase I trials showed that fixed IV doses of 100–200 mg produced minimal GI toxicities and a few objective responses: 1 CR each in NSCLC and melanoma, and 1 PR in breast cancer (Cancer Treat Sympos 1:27–35, 1985). New supplies of imexon were synthesized under a RAID grant from the NCI, allowing for a phase I dose-escalation study to be performed in patients with advanced, refractory cancers. Methods: An accelerated titration dose escalation design was chosen for the phase 1 trial using a starting dose of 20 mg/M2/day for 5 consecutive days, repeated every other week for one month. One patient per dose level is accrued until any grade 2 or greater drug-related toxicity occurs, then a standard 3 patient cohort will be used to define the MTD as any grade 3 toxicity occurring in 2/6 patients at a dose level. The primary endpoint is to establish the MTD and safety of this schedule. Secondary endpoints include imexon pharmacokinetics and RBC glutathione (GSH) levels as a possible biomarker of activity. Laboratory studies have shown a transient, dose-dependent decrease in GSH in RBC's when imexon is added to whole human blood. Results: Three dose-escalation steps have been performed without reaching the MTD. The current dose level is 80mg/M2/day. No drug-related grade 3 toxicities have occurred and the only complaints have been mild nausea. Further accrual is targeting melanoma and pancreatic cancer patients wherein orphan drug designations have been obtained for the drug from the FDA. Conclusions: The prior fixed doses of imexon do not approximate the MTD of the drug given on a daily x 5 schedule. The lack of myelosuppression, and the newly discovered mechanism of thiol oxidation makes imexon an attractive agent with to combine with other cytotoxic drugs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AmpliMed Corp. AmpliMed
Contents, Vol. 16, 1968
Authors: J Uesch, San Francisco, Cal Schmale, N Rochester, Waldau Spoerri, M Boss, Zürich Hohberger, Arnhem Van Der Horst, W Lvarez, Iii Chicago, Uppsala Annell, Zagreb Betlheim, Merida Brachfeld, Kobenhavn Bruel, Zurich Brun, Havana Bustamente, Wien Caruso, Milano Cazzullo, Paris Chertok, Anvers Ellaert, Athen Racoulides, Bonnevalle Ey, Zurich Ierz, Lisboa Fontes, London Foulkes, Wien Frankl, Wien Hoff, Glasgow Kissen, Amsterdam Lampl-Deg Root, Tübingen Langen, Paris Lebovici, Zürich Maeder, Jyväskylä Mäki, Basel Meng, Heidelberg Mitscherlich, Zürich Moor, G Moreno, Athen Philippopoulos, Marseille Schächter, Berlin Schultz, Anibal Lima, Paulo Säo, New Slavson, N York, Genève Spitz, Wien Strotzka, F Völgyesi, Budapest Wanecek, Wien Warner, Montreal Wittkower, E Carp, B Stokvis
Journal: Psychotherapy and Psychosomatics (1968)
Neoadjuvant chemoradiation therapy with gemcitabine and accelerated hyperfractionaed radiation for potentially resectable pancreatic cancer: A dose-finding study
Authors: S. Nakamori, E. Tanaka, S. Marubashi, A. Miyamoto, H. Nagano, K. Dono, K. Umeshita, M. Sakon, M. Monden
Journal: Journal of Clinical Oncology (2004)

4217 Background: Gemcitabine (GEM) has potential activity in advanced pancreatic cancer and is a portent radiosensitizer. Although neoadjuvant chemoradiation therapy with GEM is one of the promissing treatment modalities for potentially curative advanced pancreatic cancer, the tolerability and safety have been not well examined. Methods: Sequential dose-escalation of GEM (400 mg/m2 to 800 mg/m2: 0.5 hours i.v. infusion on day 1 and 7) and concomitant accelerated hyperfractionaed irradiation (1.5 Gy x2/day, 5 days/weeks, total dose 30Gy or 36 Gy) was performed for patients with potentially resectable pancretic cancer (Stage III or IV) as follows; Level 1: GEM 400 mg/m2, 30Gy, Level 2: GEM 400 mg/m2, 36Gy, Level 3: 600 mg/m2, 36 Gy, Level 4: 800 mg/m2, 36 Gy. After 3–4 weeks' rest, patients were re-evaluated for resectabilty. Minimum 3 patients were included per dosage level and recommend dose (RD) was determined. Results: A total 15 patients (2 tage III and 13 stage IV) were enrolled. Nine patients of the first 3 dose leves did not demostrated severe toxity. Leukopenia and neutropenia of grade 4 occurred in 1 of 6 patient at level 4. Clinical effects determined by CT scan included one PR, 13 SD and one PD. Reduced CA19–9 level less than a half of that at starting time was observed 12 of 15 patients. Two patients (13%) did not underwent lapalotomy due to the progressed local disease or vessel abnormality. 13 patients (87%) underwent laparotomy. Of 13 patients who have undergone laparotomy, 11 patients (85%) underwent R0 resection without any complications. 2 patients underwent paliative surgery due to M1 disease revealed at lapalotomy. During observed period (6 to 24 months), 3 patients had liver metastasis, wherase no aparent local recurrence was observed among the 11 patients who have undergone R0 resection. Conclusion: The preoperative combination of GEM and accelerated hyperfractionaed irradiation for potentially resectable pancreatic cancer is feasible and tolerated at therapeutic doses. The RD of GEM is 800 mg/m2 combined with total dose 36 Gy accelerated hyperfractionaed irradiation in this study. No significant financial relationships to disclose.
A phase II/III randomized study in advanced non-small cell lung cancer (NSCLC) with first line combination versus sequential gemcitabine and docetaxel: Interim study results
Authors: A. Mueller, N. Thatcher, C. Kortsik, G. Koschel, W. Spengler, L. Pilz, J. Mezger, C. Manegold
Journal: Journal of Clinical Oncology (2004)

7095 Background: Single-agent gemcitabine (G) and docetaxel (D) are not cross-resistant and are effective in chemotherapy-naïve and pretreated patients (pts). The study objective was to compare clinically, relevant hematologic toxicity among pts treated with G and D either in combination or sequentially. Methods: Pts on this open, randomized, multi-center trial are stratified and proceed from a sequential 4-step phase II study finally into phase III, with 327 evaluable pts planned per treatment arm. G/D is given in doses of 1000 mg/m2 /75 mg/m2/q3w in 2 study arms: A (G: days 1,8 + D: day 8 for 6 cycles) and B (G: days 1,8 for 3 cycles followed by D: day 1 for 3 cycles). Pts in Arm B switch to D earlier, upon tumor progression during treatment with G. NCI-CTC grade 3–4 thrombocytopenia/transfusion, or anemia/blood transfusion, or febrile neutropenia/antibiotics i.v. were assessed. Results: The table below shows the characteristics and interim results for 105 pts. Conclusion: These interim data suggest that sequential treatment is as tolerable and effective as combined treatment. The study continues. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly; Lilly/Aventis Lilly/Aventis Eli Lilly and Company Limited UK; Aventis Pharma Ltd UK
The Role of Aggression in Human Pathology
Authors: O.W. Schonecke, W. Schüffel, N. Schäfer, K. Winter, J.J. Groen, A. Lange, P. Visser, G. Mulder, P.C. Kuiper, H. Musaph, W. Schüffel, O.W. Schonecke, J.J. Diamant, J. Bastiaans
Journal: Psychotherapy and Psychosomatics (1972)