tbuckley/cabot-search huggingface dataset:
A phase I dose-escalation study of LY2523355, an Eg5 inhibitor, administered either on days 1, 5, and 9; days 1 and 8; or days 1 and 5 with pegfilgrastim (peg) every 21 days (NCT01214642).
Authors: K. C. Shih, J. R. Infante, K. P. Papadopoulos, J. C. Bendell, A. W. Tolcher, H. A. Burris, M. Beeram, L. Jackson, R. Arcos, E. H. Westin, D. Farrington, A. McGlothlin, S. Hynes, J. Leohr, J. T. Brandt, A. Nasir, A. Patnaik
Journal: Journal of Clinical Oncology (2011)

2600 Background: LY2523355 is an allosteric inhibitor of Eg5 which selectively inhibits bipolar mitotic spindle formation. The objective of this Phase 1 study is to determine the Phase 2 dose and schedule of LY2523355 that can be safely administered to patients with advanced malignancies. Methods: Study I1Y-MC-JFBB is an open-label, dose-escalation study in patients with advanced malignancy. The study consists of a 3+3 dose escalation phase followed by a dose confirmation phase. Eligible patients receive LY2523355 as a 1 hr infusion on either Days 1, 5, and 9; Days 1, and 8; or Days 1, and 5 with peg on Day 6; of a 21-day cycle. Due to the multiple doses per cycle schedule, the traditional maximum tolerated dose (MTD) definition was conservatively modified to include dose omissions (DO) and dose reductions (DR) in addition to standard dose limiting toxicities (DLT). Patients were assessed every 2 cycles per RECIST criteria. IHC expression of pHH3, Ki-67, and Eg5 was quantified in serial skin biopsies. Results: 46 patients have been enrolled in the study as of October 2010. The most frequent AEs (≥10%) reported include neutropenia, fatigue, nausea, vomiting, rash and anorexia. Toxicities qualifying as DLT or DR/DO were neutropenia or febrile neutropenia. To date, 16 patients have had stable disease for greater than 2 cycles. Single and multiple dose pharmacokinetics (PK) of LY2523355 and metabolite were characterized. LY2523355 clearance was dose-independent and exposure increased in a dose-dependent manner. There was negligible intra- and inter-cycle accumulation of LY2523355. Several PK and other parameters were examined for correlation with DR/DO/DLT for the Days 1, 5 and 9 and the Days 1 and 8 schedules but none were identified as significant. Eg5 inhibitor treatment-related dose and exposure dependent changes in pHH3, and Eg5 expression in skin have been demonstrated. Conclusions: Recently, the MTD for the Days 1, 5 and 9; and Days 1 and 8 schedules has been established at 8 mg/m2/d. This dose has shown a PD response in surrogate skin biopsies for both schedules. Dose escalation and expansion on the Days 1, and 5 plus peg is on-going.
Is there a predictive value for measurement of tumor percentage and the number of tumor foci after prostatectomy?
Authors: Reemt Hinkelammert, Okyaz Eminaga, Axel Semjonow
Journal: Journal of Clinical Oncology (2013)

159 Background: The prognostic relevance of tumor volume (TV), tumor percentage (TP) and number of tumor foci (NF) as predictors of biochemical recurrence (BCR) in prostate cancer (PCA) following radical prostatectomy (RPE) is controversial. Methods: The cohort consisted of 758 referred subjects who underwent RPE between 2000 and 2005 at the University of Muenster. The mean time of follow up was 62 months. TV, TP and NF were estimated visually with the assistance of a pathologic mapping grid for embedded RPE specimens. In addition, TV and TP were assessed in a categorized fashion by using medians as cut points. Subgroup analyses for high (i.e. any of the following: &gt; pT2, Gleason score ≥ 8, PSA &gt; 20 ng/ml) and low risk (not high risk) patients were performed. Univariate and multivariate Cox propotional hazard analyses for BCR were performed. Results: TV, TP, and NF were strongly related to tumour stage, Gleason score, surgical margin status (SM) and preoperative prostate specific antigen (PSA). In univariate analysis all pathologic parameters including TV, TP, and NF were predictive for BCR. In multivariate analysis only TP, tumour stage, Gleason score, and PSA level were independent predictors. In subgroup analysis, TP was an independent predictor for BCR in the high risk group, but not in the low risk group. Conclusions: TP, but not TV or NF was found to be an independent predictor for BCR in patients after RPE. TP seems to be more relevant in high risk patients.
A Genome-Wide Association Study of the Alloimmunization Responder Phenotype in Sickle Cell Disease.
Authors: Daniel A Dworkis, Nadia Timofeev, Jacqueline N. Milton, Stephen W Hartley, Mayetri Gupta, Paola Sebastiani, Clinton T. Baldwin, Efthymia Melista, Jason Parente, Karen Quillen, Martin H Steinberg
Journal: Blood (2009)
A randomized phase III trial of adjuvant chemotherapy with cisplatin and vindesine followed by UFT for completely resected pathologic (p-) stage IIIA-N2 non-small cell lung cancer (NSCLC): West Japan Study Group for Lung Cancer Surgery (WJSG) - the 5<sup>th</sup> Study
Authors: F. Tanaka, N. Tsubota, S. Namikawa, M. Ohta, M. Yamakido, S. Hitomi, H. Wada
Journal: Journal of Clinical Oncology (2005)

7262 Background: Recent clinical evidence has shown that postoperative administration of UFT, an oral 5-fluorouracil derivative agent, is an effective chemotherapy regimen for early-stage NSCLC (NEJM 2004 and ASCO 2004), but not for advanced disease. This trial was conducted to determine whether a cisplatin-based doublet (cisplatin and vindesine, PV) followed by UFT was superior to UFT alone as an adjuvant therapy for pIIIA-N2 NSCLC. Methods: Patients who underwent complete resection for pIIIA-N2 adenocarcinoma (Ad) or Squamous cell carcinoma (Sq) without any preoperative therapy were randomized to either receive 1 or 2 cycles of cisplatin (80mg/m2, day1; q4weeks) and vindesine (2–3mg/body, days 1, 8, and 15) followed by UFT (400mg/body, daily for one year) administration (PVUft group) or UFT (400mg/body, daily for one year) administration alone (UFT group). Results: Between March/1991 and March/1994, 58 eligible patients (mean age, 61 years; male percentage, 57%; Ad percentage, 78%; pT1/T2/T3, 38%/55%/7%) were randomized. Among 28 patients assigned to PVUft group, 27 (96%) and 15 (26) patients completed 1 and 2 cycles of PV, respectively; one patient did not received PV. There was no significant difference in the mean UFT dose administered to patients between both groups. Chemotherapy was well tolerated and there was no-chemotherapy related death. The 5-year overall survival rates for PVUft and UFT groups were 46% and 47%, respectively (p=0.401); the 5-year recurrence-free survival rates were 31% and 18%, respectively (p=0.163). Conclusions: No significant survival advantage was achieved by addition of PV over UFT administration alone for pIIIA-N2 NSCLC patients, whereas patients who received PV followed by UFT seemed somewhat favorable prognosis. New platinum doubles followed by UFT might be a candidate of postoperative regimen in future adjuvant trials for pIIIA-N2 NSCLC. No significant financial relationships to disclose.
Myocardial Dysfunction in Tetralogy of Fallot and Its Association With Outcome
Authors: Craig S. Broberg
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Daily patient-reported assessment of pain, anxiety, or distress, problems or concerns, and need to see physician during 100 courses of radiation therapy.
Authors: David D. Howell, Colette M. Wilson, William Andrew Moore
Journal: Journal of Clinical Oncology (2014)

193 Background: Patients (pts) undergoing radiation therapy (RT) treatment (Rx) may have pain, anxiety or distress (AoD), or other problems at the time of initiation of RT. Pts may also develop or have an exacerbation of one or more problems during RT. While undergoing RT, pts are seen weekly by the treating physician (MD), and seen daily by the treating radiation therapy technologists (RTT). Pts can develop problems between weekly MD visits which may benefit from expedited interventions. A protocol was developed where pts would be asked four questions each treatment day by the RTT: 1) Are you having pain, and if so, how would you rate it on a scale of zero to 10? (PainQ) 2) Are you having anxiety or distress today? (ADQ) 3) Are you having new problems or concerns? (ProConQ) 4) Do you want to see the physician today? (CMDQ) This information was charted, and used in pt management. Methods: 100 consecutive pt charts were reviewed for demographics including gender, age, primary malignancy, region treated, number of Rx and radiation dose. Daily answers from the four question instrument were also reviewed for each pt course of RT. Results: Of the 100 pt, 56 were male. Disease distribution: Breast-22; Prostate-20; Head and Neck-20; Lung-13; Brain-7; Other-18. For the ADQ, 83 did not report anxiety or distress; 17 reported AoD on 1-2 occasions. For the ProConQ, 35 reported none, 34 reported yes on 1-2 occasions, 22 reported yes on 3-5 occasions, and 9 reported yes on &gt;5 occasions. 29 reported yes on 2 days in a row, and 15 reported yes on 3 days in a row. For the PainQ, 31 reported no pain throughout their course of RT, with 22, 23, and 25 reporting pain of any magnitude for 1 to 5, 6 to10, and &gt;10 days, respectively. 22 reported pain level &gt; 6 on at least one occasion. For CMDQ, 26 pts did not request to see the MD greater than the usual weekly visit, 71 and 3 requested to see the MD an additional 1 to 5, and 6 to 10 times. Conclusions: A simple four question daily query of pts undergoing a course of RT is feasible, and may prompt the need for evaluation and interventions between scheduled MD visits. This may facilitate more expeditious interventions for Rx related toxicity and treatment-dependent or independent symptoms or needs.
Lower rates of acute gastrointestinal toxicity with pencil beam proton therapy relative to IMRT in neoadjuvant chemoradiation for rectal cancer.
Authors: Sonny Batra, Lauren Comisar, John Nicholas Lukens, Maura Kirk, Stefan Both, James McDonough, Najjia N. Mahmoud, Bruce J. Giantonio, Edgar Ben-Josef, James M. Metz, John Peter Plastaras
Journal: Journal of Clinical Oncology (2015)

696 Background: Preoperative chemoradiotherapy (CRT) is standard treatment for locally advanced rectal cancer (LARC). GI toxicity leading to ED visits, hospitalization, and need for IV hydration remains a management challenge. Previous studies have established volume of bowel receiving low dose radiation (V15) as the strongest predictor of GI toxicity. We have previously shown pencil beam scanned proton therapy (PBSPT) is dosimetrically superior to IMRT in LARC with respect to low dose to the bowel. This studycompares the toxicity of patients treated with PBSPT and IMRT in neoadjuvant treatment of LARC. Methods: A retrospective review was conducted of patients treated at the University of Pennsylvania with neoadjuvant 5-FU or capecitabine CRT. Patient and tumor characteristics, treatment, and toxicity data were collected. PBSPT (50.4 Gy RBE to standard volumes) was delivered using either two opposed lateral fields or posterior oblique fields with a patient supine or prone. These patients were registered on a prospective registry study. IMRT plans were delivered with 7-9 field IMRT or volumetric arc therapy in the supine or prone position. Statistical analysis was performed using STATA v12.0. Results: Between 3/2009 and 6/2014, 39 patients treated with IMRT and 26 patients treated with PBSPT were studied. Continuous-infusion 5-FU was administered in 31 (79%) IMRT patients and 16 (62%) PBSPT patients (p = 0.162); the remainder received capecitabine. PBSPT patients had significantly lower rates of acute Grade ≥ 2 diarrhea, 12% versus 39% with IMRT (p = 0.022). On multivariable analysis incorporating the type of chemotherapy, use of PBSPT remained a significant predictor of lower rate of Grade ≥ 2 diarrhea (OR = 0.20, 95% CI 0.05 - 0.82, p = 0.025). There was also a borderline significant reduction in Grade ≥ 2 fatigue with the use of PBSPT, occurring in 8% versus 29% of IMRT patients, p = 0.057. Conclusions: These preliminary results indicate PBSPT is associated with significant reduction in acute Grade ≥ 2 diarrhea compared to IMRT. PBSPT may play an important role in the treatment of LARC, a disease with high cure rate where radiation toxicity should be minimized.
A randomised phase II study of gemcitabine versus mitomycin C versus gemcitabine/mitomycin C in patients with advanced pancreatic cancer
Authors: G. Tuinmann, L. Mueller, D. Hossfeld, C. Bokemeyer
Journal: Journal of Clinical Oncology (2008)

15658 Background: The prognosis of patients with advanced pancreatic cancer remains poor. However, chemotherapy can improve life quality and median survival. We have shown that the combination of gemcitabine and mitomycine has a tolerable toxicity profile. It can be easily administred in an outpatients setting. Based on our previous results a multicenter randomised phase II study was initiated. Primary aim was to demonstrate a longer progression free survival time for patients, who were treated with the combination of Gemcitabine (GEM)/Mitomycin C (MMC) compared to those receiving monotherapy with either agent. Secondary aims were response rates, toxicity and influence on life quality. Methods: Recruitment started in 02/04. Meanwhile 69 patients (of planned 138 in total) were enclosed. Patients older than 18 years with stage III or IV pancreatic adecarcinoma were randomised into ARM A (24 patients; GEM 800mg/m2, d 1,8,15 + MMC 6mg/m2, d1; q29), into ARM B (23 patients; MMC 10mg/m2 d1, q29) or ARM C (22 patients; GEM 1000mg/m2 d 1,8,15). Altogether 6 cycles were scheduled in all treatment arms. Results: Mean age was 64 years. 10% of the patients had locally advanced and 90% metastatic tumors. A medium of 3 cycles were given in ARM A, and a medium of 2 cycles in both ARMs B and C. Medium time to progression was 3 months in ARM A, 1.7 months in ARM B and 1.8 months in ARM C. Medium overall survival times were 7 months in ARM A, 3,1 months in ARM B and 2.8 months in ARM C. Hemotological toxicity was moderate with no grade 4 toxicity. Grade 3 thrombopenia (15%) did not result in bleeding complications and there was no case of neutropenic fever or sepsis in patients with grad 3 leukopenia (7%). There were no cases of HUS. Pneumonitis 1° and 2° occurred in 2 patients (Arm A). 5 patients are alive (ARMs A+C: 3 patients, ARM B; 1 patient) with a medium follow up of 4 months. Conclusions: Due to the limited number of patients no definite conclusions can be drawn. However the interim analysis shows that the combination of GEM/MMC is a safe and beneficial treatment modality in patients with advanced pancreatic cancer. Additionally the monotherapies of MMC vs. GEM are not significantly different. A statistical analysis and an update will be presented at the meeting. No significant financial relationships to disclose.
David Howel Bayton
Authors: Evan Aled Bayton
Journal: BMJ (2017)

After Swansea Grammar School, David Howel Bayton studied at St Thomas’ Hospital, at a time when many of his contemporaries were former servicemen. He greatly valued the experience of life that he heard from these men. He represented St Thomas’ at football and cricket and also acted as fixtures secretary for the teams. On qualifying he considered a career in paediatrics and took a post as house surgeon at the Royal Manchester Children’s Hospital, Pendlebury, later transferring to the HP post. He did national service in the Royal Army Medical Corps at …
Prostate-specific mRNA detection in whole blood as an analytically validated prognostic biomarker for patients with castration-resistant prostate cancer (CRPC).
Authors: Aseem Anand, Daniel Costin Danila, Glenn Heller, Amrita Herkal, Chintan Patel, Raya Khanin, Nikolaus Schultz, Hans Lilja, Martin Fleisher, Howard I. Scher
Journal: Journal of Clinical Oncology (2013)

5032 Background: Detection of prostate-specific transcripts in blood has been associated with survival, but validated assays are lacking. We analytically validated a qPCR-based assay in CLIA environment to detect prostate cancer enhanced transcripts in whole blood and determine its prognostic significance relative to circulating tumor cell (CTC) enumeration. Methods: Blood was collected from patients with progressive CRPC in PAXgene tubes for total RNA extraction. Five genes overexpressed in prostate tissue, KLK3, KLK2, HOXB13, GRHL2, and FOXA1, were analyzed by RT-qPCR. Each qPCR-reaction was performed in 6 replicates and detection thresholds for each gene were chosen by receiver operator curve analysis. Detection rates were compared to enumeration using CellSearch in an independent data set of 97 CRPC patients and survival associations explored by concordance probability estimate (CPE). Results: Two or more genes were detected by qPCR in 53% (51 of 97, 95% CI 43-63%) of patients, and unfavorable CTC counts (≥5cells) were seen in 46% (45 of 97, 95% CI 36–56%). Transcripts were detectable in 21% (11 of 52, 95% CI 8–35%) of patients with favorable CTC counts (≤4). Similar to CTC enumeration, transcript detection predicted overall survival in a proportional hazards model. The predictive accuracy of qPCR detection in combination with CTC enumeration had a CPE of 0.752 (SE=0.038). Conclusions: This validated RT-qPCR assay detects prostate-specific mRNA in whole blood in more patients than CellSearch, is prognostic for survival, and may assess patient risk in conjunction with CTC enumeration. Its clinical utility will be prospectively explored. Supported by NCI SPORE in Prostate Cancer (P50 CA92629); the Department of Defense Prostate Cancer Research Program; Prostate Cancer Foundation; Mr. William H. and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research and The Experimental Therapeutics Center; DoD Prostate Cancer Research Program Physician Research Award W81XWH-09-1-0307.
Comparison of predictive and prognostic impact of molecular subtypes and central grade regarding taxane-based therapy in intermediate-risk breast cancer: Results from the EC-Doc trial.
Authors: U. Nitz, O. Gluz, C. Liedtke, J. B. Huober, A. Hartmann, R. E. Kates, H. H. Kreipe, E. Pelz, W. Kuhn, N. Harbeck
Journal: Journal of Clinical Oncology (2011)

10625 Background: Patients with hormone receptor positive breast cancer and 1-3 positive lymph nodes (LN) belong to the intermediate risk-group. Among these patients chemo-endocrine therapy may be considered according to the St. Gallen guidelines. We compared evidence-based cut-offs of Ki-67 for definition of molecular subtypes to central grade regarding their predictive value for benefit from taxane-based chemotherapy. Methods: The EC-Doc trial randomized 1950 patients with 1-3 positive LN to 6x CEF/CMF vs. 4xEC-4xDoc. Significantly better DFS and OS favoring EC-Doc have been previously reported (Nitz et al., SABCS 2008). Protein expression data (ER, PR, HER2[+FISH], Ki-67, Ck 5, and EGFR) and central histology/grade were available for 772 patients. Molecular subgroups were classified using Ki-67 cut-off’s of 13.25% and 20% (due to correlation with genomic grade index [GGI]). GGI analysis is planned. Results: The entire and the investigated study populations did not differ regarding baseline characteristics. After median follow up of 64 months, both DFS (5y 90% vs. 80%, p=0.006) and OS (5y 95% vs. 92%, p=0.022) rates significantly favored EC-Doc vs. CEF also in this cohort. 5-y DFS was longest in luminal A and shortest in basal-like tumors (97% vs. 72%, p<0.001). Both Ki-67 cut-offs (13.25% and 20%) used for defining luminal B subtype were predictive for taxane benefit. However, only Ki-67 cut-off of 20% was significant regarding interaction with therapy (HR=0.467, p=0.02) in multivariate analysis including central grade, age, nodal status, tumor size, molecular subtypes, therapy, and predictive interactions between all factors and therapy. Only central grade (HR=4.315, p<0.001) and luminal A subtype (HR=0.343, p<0.001) were shown as significant prognostic factors for the whole collective. Conclusions: These data provide evidence that luminal B subtype defined by HR positive and KI-67>20% or HER2+ is the only predictive factor for taxane benefit in intermediate risk BC and that both central grade and luminal A subtype are strong prognostic markers. These results are currently validated within the prospective WSG PlanB trial.
Two-year outcomes of a prospective study of proton therapy for breast cancer regional nodal irradiation.
Authors: Julie Ann Bradley, Roi Dagan, Meng Wei Ho, Michael Scott Rutenberg, Zuofeng Li, Nancy P. Mendenhall
Journal: Journal of Clinical Oncology (2015)

65 Background: Through improved nodal coverage and decreased dose to the heart and lung, proton therapy (PT) may improve the therapeutic ratio for treatment of breast cancer requiring regional nodal irradiation (RNI). The purpose of this study is to report 2-year disease control and toxicity. Methods: From May 2012 to February 2014, 18 women (stage IIA-IIIB) were prospectively enrolled on a pilot study. Median age was 51.8 yrs (range, 42-73), with equal division between breast-conserving therapy (BCT) and mastectomy and right- and left-sided cancers. Median number of positive nodes among the 16 node-positive patients was 2 (range, 1-14). Five patients had ≥ 10 nodes positive on axillary dissection (N3a). Treatment targets (clinical target volumes for breast/chest wall, supraclavicular, axillary, internal mammary nodes) and organs at risk were delineated on CT scans. PT alone was used for 10 patients (9 postmastectomy; 1 postBCT) and combined proton-photon in 8 (all BCT). Toxicity was prospectively recorded using CTCAE v4.0. Results: Median follow-up was 1.9 yrs (range, 0.3 – 1.7). Two-year overall survival was 94% and locoregional control was 100%. Two-year distant metastases-free survival was 76%. No grade 4+ toxicity developed. Two patients developed grade 3 cellulitis. One patient had a reconstructive failure associated with postsurgical cellulitis. A right-sided patient was diagnosed with congestive heart failure 2 months after completing PT after diagnosis of a pulmonary embolus 1 month prior. She had elevated B-type natriuretic peptide before PT after adriamycin-based chemotherapy. Mean heart dose was 0 Gy and cardiac V5 0%. Grade 2 toxicities included pneumonitis in 1 patient who received concurrent chemotherapy, fatigue (n = 1), breast atrophy after removal of a 10x6x3cm lumpectomy cavity (n = 1), and lymphedema in 1 patient with &gt; 20 nodes surgically excised. One patient with a history of rib fractures developed an ipsilateral rib fracture 7 months after PT. Conclusions: For women with locally advanced breast cancer, PT for RNI has proven feasible after either mastectomy or BCT. PT allows for highly conformal radiation delivery without compromise of target coverage or excess exposure of normal tissue. Clinical trial information: NCT01365845.