tbuckley/cabot-search huggingface dataset:
ROCHOP study: A phase III randomized study of CHOP compared to romidepsin-CHOP in untreated peripheral T-cell lymphoma.
Authors: Richard Delarue, Pier Luigi Zinzani, Mark S. Hertzberg, Won Seog Kim, Dolores Caballero, Antonio Pezzutto, Marc Andre, Maria Gomes Da Silva, Philippe Gaulard, Bertrand Coiffier
Journal: Journal of Clinical Oncology (2013)

TPS8616 Background: Peripheral T-cell lymphomas (PTCL) account for 10-15% of lymphomas. They share an aggressive clinical behaviour and a poor prognosis when treated by CHOP-like regimen which is nevertheless consider as a standard because others regimens failed to demonstrate survival advantage. Romidepsin is a histone deacetylase inhibitor with promising results in PTCL. First trials showed a response rate of 38% in heavily pre-treated PTCL patients. These results were confirmed with 15% of patients reaching a CR/CRu, 89% of them without disease progression at 13 months. Adverse events include gastrointestinal, hematologic and asthenic conditions. A phase I study of romidepsin combined with CHOP was conducted by LYSA. A total of 18 patients were included. The recommended dose was 12 mg/m² administered at day 1 and day 8 of each cycle. Methods: Ro-CHOP study is an international phase III study comparing 6 cycles of CHOP21 with 6 cycles of romidepsin-CHOP21 (EUDRACT 2012-001580-68). Primary endpoint is Progression-Free Survival assessed independently. Secondary objectives include overall survival, other efficacy parameters, analysis of response rate according to 18 FDG-PET, safety, quality of life and biological ancillary studies. A total of 420 subjects aged from 18 to 80 years will be enrolled in the study. Main inclusion criteria are untreated PTCL whatever Ann Arbor stage and a performance status of 0-2. Main exclusion criteria are other subtypes of lymphoma, HTLV1 positivity, any cardiac abnormality, poor renal, hepatic and marrow functions unless related to lymphoma. Patients are randomized 1:1 between the two regimens. A stratification is performed with IPI score, age and histology. The first patient has been included in January 2013. A recruitment of 10.5 patients per month is anticipated, with a total duration of the study of 60 months. An update on enrolment will be presented at the meeting. Clinical trial information: 2012-001580-68.
Genetic Profiling of Adult Acute Lymphoblastic Leukemia Cells by Single Nucleotide Polymorphism Oligonucleotide Microarray.
Authors: Ryoko Okamoto, Seishi Ogawa, Tadayuki Akagi, Motohiro Kato, Masashi Sanada, Carl W. Miller, Norihiko Kawamata, Claudia Haferlach, Torsten Haferlach, H. Phillip Koeffler
Journal: Blood (2007)
Improvement in sexual function after ovarian cancer: Sexual therapy and rehabilitation after treatment for ovarian cancer (START-OC).
Authors: Sharon L. Bober, Christopher J. Recklitis, Alexis L. Michaud, Alexi A. Wright
Journal: Journal of Clinical Oncology (2017)

210 Background: Sexual dysfunction is a distressing long-term effect after ovarian cancer (OC), affecting up to 90% of survivors for years. Despite its prevalence, treatment-related sexual dysfunction is underrecognized and undertreated for OC survivors. We developed and tested a brief, psychoeducational intervention for managing sexual dysfunction after OC. Methods: 45 OC survivors with sexual dysfunction received a single half-day group intervention that included sexual health education, relaxation and cognitive behavioral therapy (CBT) skills to address sexual symptoms and a single tailored telephone booster call 4 weeks post-group. Assessment measures were completed at 4 time points: Baseline 1, Baseline 2 (after an 8 week no-treatment run-in period), and 2 and 6 months post-intervention. The Female Sexual Function Index (FSFI) assessed sexual functioning and the Brief Symptom Inventory (BSI-18) captured psychological distress. Results: Analyses examined changes from Baseline 1 to subsequent time points. Between Baseline 1 and 2 there were no significant changes on study measures, indicating no natural improvement during the run-in period. In contrast, Total FSFI scores improved significantly from Baseline 1 to the 2 month (n = 45, p &lt; .005) and 6 month (n = 35, p &lt; .05) follow-ups. Effect sizes were moderately large indicating a significant improvement in women’s sexual function post- intervention (d = .5) that was sustained for at least 6-months (d = .4). BSI-18 scores were also significantly improved at the 2 -month (p &lt; .005) and 6 month (p &lt; .01) time-points, compared to Baseline 1. Conclusions: Improvements in overall sexual functioning and psychological distress were observed 2 months post-intervention and maintained at 6 month follow-up, suggesting preliminary efficacy of the intervention in reducing sexual dysfunction in OC survivors. Next steps include collection of additional follow-up data on participants. A randomized trial of START-OC is warranted. Clinical trial information: NCT02287519.
Patient selection using novel RNA-based approaches: Early experience from a phase I study with the pan-FGFR inhibitor BAY 1163877 in patients with urothelial bladder cancer.
Authors: Markus Joerger, Martin H. Schuler, Philippe Alexandre Cassier, Sandra Hildebrandt, Simone Behre, Corinna Helmbrecht, Stephanie Kerpen, Dirk Zielinski, Stuart Ince, Matthias Ocker, Peter Ellinghaus
Journal: Journal of Clinical Oncology (2017)

386 Background: FGFRs play a role in a variety of malignancies, including urothelial bladder cancer (UBC). Whereas genetic alterations of FGFRs in UBC are known, non-genetic and epigenetic activation of FGFR gene expression have also been described. BAY 1163877 is an oral inhibitor of FGFRs 1-3 with antitumor activity in FGFR mRNA overexpressing xenograft models not limited to DNA alterations. We report the results from a phase I expansion cohort in UBC patients pre-screened for treatment with BAY 1163877 based on FGFR1-3 mRNA overexpression and/or activating mutations in the FGFR3 gene. Methods: FGFR mRNA levels were assessed in paraffin-embedded archival or fresh biopsy specimens by RNAscope and NanoString technology and activating mutations by RT-PCR-based mutation assay. Tumor response to treatment was assessed by RECIST, v1.1. Adverse events were assessed using CTCAE v4.03 criteria. Results: A total of 80 patients from multiple indications were enrolled in the phase I study; 800 mg BID was established as the recommended phase 2 dose. Sixty seven UBC patients were screened, with 31 tumor biopsies (46%) determined to overexpress FGFR mRNA: 2 patients each with FGFR1 and FGFR2, and 27 patients with FGFR3. Of the 27 patients with FGFR3 mRNA overexpression, 5 had in parallel an activating mutation in FGFR3 gene. Eight UBC patients met eligibility criteria and entered treatment; all had elevated FGFR3 mRNA expression and 4 had alterations in FGFR3 DNA (3 mutations and 1 translocation). Seven patients (87.5%) had tumor shrinkage in target lesions as best response, with 3/8 partial responses (PR; 37.5%). One patient with a PR presented with elevated FGFR3 mRNA without evidence of aberrant DNA. BAY 1163877 was generally well tolerated and AEs manageable with dose modification. The most common AEs in the overall population were increased phosphorus (66% all grade, 1 grade-3 event) and diarrhea (33% all grade, 2 grade-3 events). Conclusions: Selection of patients for treatment with BAY 1163877 based on FGFR mRNA expression levels in archival tissue was feasible. BAY 1163877 had a favorable safety profile and promising anti-tumor activity in UBC patients. Clinical trial information: NCT01976741.
Does menopausal status influence the symptom experience of women prior to breast cancer surgery?
Authors: Melissa Mazor, Steven M. Paul, Christine Miaskowski
Journal: Journal of Clinical Oncology (2017)

149 Background: Breast cancer treatments can change women’s hormonal milieu and alter their symptom experience. Little is known about associations between menopausal status and menopausal symptoms in women with breast cancer prior to treatment with surgery, chemotherapy, and/or hormonal therapy. The purpose of this study was to evaluate for differences in menopausal symptom experience between pre- and post-menopausal women prior to breast cancer surgery. Methods: A total of 312 women with breast cancer completed the Menopausal Symptoms Scale, a self-report measure that evaluates the occurrence, severity, and distress of 46 common symptoms associated with menopause. Results: Of the 312 patients enrolled, 37.4% (n=116) were premenopausal and 62.6% (n=196) were postmenopausal. No differences were found in the total number of symptoms reported between premenopausal (x̅ = 13.3±7.8) and postmenopausal (x̅ = 12.0±8.6; t = 1.35, p=.177) patients. Premenopausal patients reported higher occurrence rates for tearful/crying spells, painful/tender breasts, anxiety, lost interest in things, anger, tension, lost sexual interest, fatigue or tiredness, impatience, headache, and nervousness (p&lt;.05 for all). Premenopausal patients reported lower occurrence rates for joint pain/stiffness (p=.011), difficulty falling asleep, vaginal dryness, daytime sweats, and hot flashes (p&lt;.01 for all). A significant interaction was found between age and menopausal status. In the premenopausal group, as age increased, these women were significantly more likely to have hot flashes (p=.033). In the postmenopausal group, as age increased, these women were significantly less likely to have hot flashes, wake during the night, have headaches, and report nervousness (p&lt;.01 for all). In the bivariate and multivariate analyses, none of the symptom severity or distress scores were significantly different between the pre- and post-menopausal patients. Conclusions: Findings from this study suggest that, regardless of menopausal status, women report a high occurrence of menopausal symptoms. The association between menopausal symptom occurrence and menopausal status depends on the specific menopausal symptom and the patient’s age. Clinical trial information: NCT00769821.
Patterns of ipilimumab (IPI) usage and health care resource utilization in a retrospective analysis of patients (pts) with melanoma covered in a large U.S. claims database.
Authors: Eric D. Whitman, Xiting Cao, Kendall Lee Stevinson, Ashwini Arunachalam, Panagiotis Mavros
Journal: Journal of Clinical Oncology (2015)

e20028 Background: In 2011, the FDA approved the anti–CTLA-4 antibody IPI for the treatment of unresectable or metastatic melanoma. Real-world data on the use of IPI are lacking. Using the Truven Health MarketScan commercial and Medicare supplemental database, we retrospectively examined patterns of IPI usage and health care resource utilization among IPI-treated pts. Methods: Subjects included in the analysis had a confirmed melanoma diagnosis, were aged ≥ 18 y, had ≥ 1 claim with a National Drug Code (NDC) or J code for IPI between Mar 1, 2011, and Mar 31, 2013, and were continuously enrolled in the database during the 6-mo period before the earliest code for IPI. Pts were followed until Dec 31, 2013. Health care resource utilization included inpatient admissions, outpatient visits, imaging procedures, therapeutic interventions, and diagnostic procedures. Concomitant medication usage and known complications associated with IPI were also examined. Results: A total of 805 pts met the inclusion criteria and were included in the analysis. Mean age was 59.0 y, and 63% of pts were men. 44% of pts received 4 IPI doses; 49% received ≤ 3 doses, and 7% received ≥ 5 doses. Median duration between doses was 21 d in pts who received ≤ 4 doses. Within 24 wk of the first IPI dose, newly initiated therapies included corticosteroids in 30%; anti-emetics in 22%; anti-infectives in 14%; antidiarrheals, antidepressants, and hormone/synthetic substances in 4%; and infliximab in 1%. Pulmonary, gastrointestinal, dermatologic, and endocrine complications were reported for 64%, 60%, 43%, and 23% of pts, respectively. The proportion of pts with concomitant medication use and complications increased from doses 1-3, but decreased for those who received 4 doses. 45% of pts had ≥ 1 hospitalization. Hospitalization rate was 0.51 per 100 patient days; the average duration per admission was 7.7 d. 23% of pts had ≥ 1 emergency department visit. Conclusions: This analysis reveals real-world patterns of IPI usage in pts with advanced melanoma. Data suggest that many IPI-treated pts require concomitant medications and experience complications known to be associated with IPI.
Demographics, tumor characteristics, and clinical outcomes associated with somatic mutations in 201 cancer-related genes in advanced melanoma patients (pts).
Authors: Michael A. Davies, Aron Joon, Roland L. Bassett, Jason Roszik, Alan Siroy, Lauren Elaine Haydu, Ken Chen, Franceso Stingo, Veera Baladandayuthapani, Kenna Rael Shaw, Funda Meric-Bernstam, Michael T. Tetzlaff, Jeffrey E. Gershenwald, Scott Eric Woodman, Alexander J. F. Lazar
Journal: Journal of Clinical Oncology (2015)

9057 Background: Cutaneous melanomas (CM) have a high rate of somatic mutations. We analyzed the prevalence and correlations of mutations in 201 cancer-related genes to identify clinically significant molecular events in a cohort of pts with advanced melanoma. Methods: Next generation sequencing (NGS) of all exons of 201 cancer-associated genes was performed on tumor and germline DNA from pts with a known primary non-acral CM enrolled in an IRB-approved research protocol. Demographics, primary tumor characteristics, date of diagnosis of stage IV disease, and overall survival (OS) were collected for all pts. The significance of associations between these characteristics and somatic mutations was analyzed by a variety of statistical methods. Results: NGS was performed on 106 advanced melanoma pts with a known non-acral primary CM. Genes with a mutation rate > 10% (n = 74) were assessed for clinical associations. NF1 (OR 12.9, p = 0.002) and PCLO (OR 3.1, p = 0.01) mutations were associated with male gender, while BRAF V600 mutations were more common in women (OR 0.38, p = 0.03). BRAF mutations were associated with younger age at diagnosis (p < 0.0001), and 12 genes were associated with older age. Mutations in 5 genes were associated with increased primary tumor Breslow thickness, most significantly MET (mean 8.3 vs 3.5 mm, p = 0.005). Among all pts with NGS data with distant metastases (n = 88), NRAS mutation was associated with significantly shorter OS from the diagnosis of stage IV (HR 3.2, p = 0.007), while mutations in BRAF (HR 0.35, p = 0.02) and 12 other genes were associated with significantly longer OS (HR 0.12 to 0.40). Among stage IV pts without BRAF V600 mutations (n = 52), NRAS mutation was again a significant predictor of shorter OS (HR 2.8, p = 0.04), and mutations in 12 other genes correlated with increased OS (HR 0.11 to 0.37). Conclusions: Somatic mutations in several genes in advanced non-acral CM pts were significantly associated with disease characteristics and clinical outcomes, and merit analysis in additional cohorts of pts. Analysis of copy number variations will be included in the final report for the cohort.
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Standard Reporting and Evaluation Guidelines
Authors: Emanual Maverakis, Elizabeth A. Wang, Kanade Shinkai, Surakameth Mahasirimongkol, David J. Margolis, Mark Avigan, Wen-Hung Chung, Jennifer Goldman, Lois La Grenade, Munir Pirmohamed, Neil H. Shear, Wichittra Tassaneeyakul, Wolfram Hoetzenecker, Jettanong Klaewsongkram, Ticha Rerkpattanapipat, Wiparat Manuyakorn, Sally Usdin Yasuda, Victoria R. Sharon, Andrea Sukhov, Robert Micheletti, Jeff Struewing, Lars E. French, Michelle Y. Cheng
Journal: JAMA Dermatology (2017)

Toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS) are rare, acute, life-threatening dermatologic disorders involving the skin and mucous membranes. Research into these conditions is hampered by a lack of standardization of case reporting and data collection.To establish a standardized case report form to facilitate comparisons and maintain data quality based on an international panel of SJS/TEN experts who performed a Delphi consensus-building exercise.The elements presented for committee scrutiny were adapted from previous case report forms and from PubMed literature searches of highly cited manuscripts pertaining to SJS/TEN. The expert opinions and experience of the members of the consensus group were included in the discussion.Overall, 21 out of 29 experts who were invited to participate in the online Delphi exercise agreed to participate. Surveys at each stage were administered via an online survery software tool. For the first 2 Delphi rounds, results were analyzed using the Interpercentile Range Adjusted for Symmetry method and statements that passed consensus formulated a new case report form. For the third Delphi round, the case report form was presented to the committee, who agreed that it was "appropriate and useful" for documenting cases of SJS/TEN, making it more reliable and valuable for future research endeavors.With the consensus of international experts, a case report form for SJS/TEN has been created to help standardize the collection of patient information in future studies and the documentation of individual cases.
Driving up the adenoma detection rate: is it time to make a U-turn?
Authors: Jonah Cohen, Mandeep Sawhney
Journal: Endoscopy (2017)

Colon cancer is the second most common cause of cancer-related death for both men and women in the United States [1]. Colonoscopy with polypectomy has been proven to substantially reduce the incidence and mortality associated with the disease [2], but colonoscopy appears to be less effective in preventing right-sided colon cancers [3] [4] [5] [6]. Studies have shown that interval colon cancers are almost twice as likely to occur in the right colon, and may represent a biologically distinct subset with regard to demonstrating higher rates of microsatellite instability and CpG island methylator phenotype [7]. Studies have also suggested that polyps with advanced histology are smaller in size, and more likely to be sessile in the right colon than in the left colon [8] [9]. Furthermore, the right colon is technically more difficult to examine during colonoscopy [10]. Repeat examination of the right colon to improve the detection of polyps is therefore considered. The repeat examination can be done in a standard forward-view manner, or the colonoscope can be retroflexed in the cecum and the right colon examined in a retroflexed manner. Retroflexion has the theoretical advantage of being able to visualize the back-side of haustral folds and flexures, mucosa that can be difficult to examine in the forward-view position. Retroflexion however is not always possible, because of colon anatomy, a looped position of the colonoscope, and operator inexperience; and it is also associated with a small risk of perforation [11].
Richard R. Rubin, PhD: An Ambassador for Behavioral Science in Diabetes
Authors: Mark Peyrot
Journal: Diabetes Care (2017)

Richard Roy Rubin, PhD, (“Dick” to many of his friends) was born in Lima, Peru, to Goldie (Possoff) and Morton Rubin. Goldie attended Temple University, while Morton attended Penn State and Massachusetts Institute of Technology (MIT), where he specialized in southern hemisphere weather. Morton’s job of forecasting weather for Pan American-Grace Airways (Panagra) afforded the young couple the opportunity to relocate several times in their early years. They were living in Lima when Richard was born in 1943 and in Santiago, Chile, when Richard's brother John was born in 1946. It was back to the U.S. (Waltham, MA) in 1948, where sister Mary Sue was born the following year. The now-complete family moved to Pretoria, South Africa, in 1954. Mary Sue relates that one of Richard's favorite memories was when Morton took the boys to Kruger National Park, about 250 miles from Pretoria, where they slept in thatched huts and listened to lions, hyenas, and other wildlife throughout the night. Though Morton and Goldie were of Lithuanian and Ukrainian descent and spoke English and Yiddish, all the family members became quite fluent in Spanish during their years in South America. The family came back to the U.S. in 1955 and eventually settled in Bethesda, MD, in 1959.

That same year, after 16 months of research in Antarctica, Morton Rubin arrived home to find his 9-year-old daughter in the hospital with a diagnosis of type 1 diabetes. Richard remembered it as a devastating blow to the family (Mary Sue was the first in her extended family to be diagnosed with the disease [1]). Mary Sue’s diagnosis, and later Richard's own son’s diagnosis, would be reason enough to turn his career path to the field of diabetes. In 1961, Richard moved to Baltimore to attend Johns Hopkins University (JHU).

Initially, …
Customization of treatment for patients with esophageal adenocarcinoma (EAC) who achieve clinical complete response (cCR) after chemoradiation using initial standardized uptake value (iSUV) of <sup>18</sup>f-fluorodeoxyglucose PET.
Authors: Akihiro Suzuki, Lianchun Xiao, Takashi Taketa, Mariela A. Blum, James Welsh, Steven H. Lin, Brian Weston, Jeffrey H Lee, Manoop S. Bhutani, David C. Rice, Reza J. Mehran, Dipen M Maru, Jeremy J. Erasmus, Wayne Lewis Hofstetter, Stephen Swisher, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2012)

4069 Background: Patients with localized esophageal adenocarcinoma (EAC) receive preoperative chemoradiation followed by surgery (trimodality [TM] therapy) or definitive chemoradiotherapy (bimodality [BM] therapy) based on comorbidities and tumor geography. However, we cannot individualize recommendations beyond these parameters. We hypothesized that iSUV could customize therapy. Methods: Data source was our prospective database of fully staged EAC patients (2002-2010). All patients had a cCR (post-chemoradiation negative biopsy and post-chemoradiation physiologic uptake on PET). iSUV cut-point was derived by recursive partitioning. Results: For 323 cCR patients, the median follow-up was 40.8 months. 206 (63.8%) patients had TM and 117 (36.2%) had BM therapy. Median OS of TM patients and BM patients were 94.8 months (95 % CI; NA-NA) and 36.5 months (95% CI; 30.5-42.4; p&lt;0.001), respectively. Similar differences were observed in RFS (p&lt;0.001). The median iSUV was 9.4 (range, 0-58.0). Intriguingly, TM patients with iSUV of &gt;6 had a better OS (94.8 months; 95% CI; 39.1-150.5) and RFS (94.8 months; 95% CI; 18.2-171.4) compared to BM patients with iSUV of &gt;6 OS (31.4 months; 95% CI; 21.0-41.9; p=&lt;0.001) and RFS (17.2 months; 95% CI; 14.5-19.8; p&lt;0.001). However, the prognosis of TM and BM cCR patients with iSUV &lt;6 was similar (OS, p=0.62 and RFS, p=0.46). The pathological CR (pathCR) rate in TM patients was similar irrespective of iSUV of ≥6 (27.1%) vs. iSUV &lt;6 (28.6%; p=0.85). Conclusions: Our unique data provide an insight into the fate of cCR EAC patients by iSUV. Patient with iSUV ≥6 dramatically benefit from surgery and TM therapy is encouraged. iSUV and pathCR do not correlate. iSUV can customize therapy of localized EAC patients.