tbuckley/cabot-search huggingface dataset:
Pegylated liposomal doxorubicin for adjuvant treatment of breast cancer in patients refusing therapy with conventional doxorubicin.
Authors: P. Manente, G. Vicario, G. Sgarbossa, F. Girardi, M. Bortolin, E. Scelzi, L. Sartor, G. Vultaggio
Journal: Journal of Clinical Oncology (2010)

e11097 Background: Doxorubicin is a drug of primary importance in the adjuvant chemotherapy of breast cancer. The most frequent side effects besides myelotoxicity are alopecia and cardiotoxicity. The latter influences the treatment plan in pts candidated to treatment with potentially cardiotoxic drugs such as trastuzumab. Recently, women have a stronger consciousness on therapeutic options and theray-related side effects, due to improved access to press or internet, and ask the physician for less toxic treatment, to avoid cardiotoxicity and alopecia, due to availability of liposomal doxorubicin, less cardiotoxic (Doxil, Myocet) and devoid from effects on hair loss (Doxil). Liposomal doxorubicin is not a standard treatment for adjuvant CT in breast cancer. We report on our experience of use of Doxil (PLD) due to clear patient request. Methods: From June 2007 to December 2009, 30 patients have been treated with PLD. The reasons for this choice are: refusal of the risk of alopecia in 11 pts; refusal of the risk of cardiotoxicity in 13 pts; a treatment plan implying the use of trastuzumab in 6 pts. Median age was 47 (26-62); ECOG PS = 0; breast cancer stage I and II; 19 pts with N1 disease (2 with more than 3 positive nodes); 24 pts hormone receptor +; 7 pts HER-2 +. CT schedules: FDC (5-FU 600 mg/m2, Doxil 35 mg/m2, CTX 600 mg/m2) in 23 pts; DC (Doxil 40 mg/m2, CTX 600 mg/m2) in 7 pts. Results: All the pts have completed the CT for a total of 160 courses (6 courses in 19 pts; 4 courses in 11 pts), without any dose reduction, but with a 7-day delay in 32 courses due to grade 3 neutropenia. Alopecia G1 was observed in 1 pt and G2 in 2 pts. The most frequent side- effect has been Hand Foot Syndrome (HFS): G1 in 12 cases; G2-G3 in 16 cases; G3-G4 in 2 pts. We did not observed any cardiac dysfunction, evaluated through echocardiography. At the present time all the pts are alive, but 2 of them show progressive disease. Conclusions: Our data show that Doxil-based chemotherapy in the adjuvant setting is feasible, with an toxicity similar to that observed with conventional doxorubicin. Alopecia was sporadic and mild. We did not observed cardiotoxicity. HFS is the most frequent side effect, it was mild to moderate and easily manageable. No significant financial relationships to disclose.
A randomized phase 2 study of the thrombospondin-mimetic peptide ABT-510 in patients with previously untreated advanced renal cell carcinoma
Authors: S. W. Ebbinghaus, M. Hussain, N. M. Tannir, M. S. Gordon, A. A. Desai, R. A. Knight, D. M. Carlson, R. A. Figlin
Journal: Journal of Clinical Oncology (2005)

4607 Background: ABT-510 is a potent nonapeptide that mimics the antiangiogenic activity of the naturally occurring protein, thrombospondin-1. In 2 phase 1 studies in patients with solid tumors, ABT-510 was tolerated at doses up to 260 mg per day. The pharmacokinetic target of 100 ng/mL for >3 hours was achieved at doses ≥20 mg per day. Six of 13 patients (46%) with refractory renal cell carcinoma (RCC) were progression-free for 16 or more weeks on study. A phase 2 study evaluating the activity of ABT-510 in the first-line treatment of patients with advanced RCC has completed accrual. Methods: 103 patients were randomized to receive ABT-510 at 10 mg or 100 mg twice daily by subcutaneous injection. Dosing is continuous. The primary endpoint of the study is progression-free survival (PFS); secondary endpoints include response rate, overall survival, and performance status. Tumor progression is evaluated every 8 weeks by RECIST; safety is evaluated at every visit. Results: 103 patients are enrolled in the study; 42 remain active. Demographic data are available for 87 patients (55M/32F); the median age is 58 years (range 20–80), and the baseline ECOG Performance Score for all patients is 0 or 1. For the 88 patients with preliminary data, the 6-month progression-free rate is 24.6% (95% CI=11.9, 37.3). One confirmed partial response has been observed. The most frequent adverse events (AEs) include injection site reaction, asthenia, and pain. There were 314 reported AEs, of which 32 (10%) were serious adverse events (SAEs). 7 SAEs were possibly or probably drug-related. These included 2 events related to bleeding (hemoptysis, gastrointestinal hemorrhage) and 1 thrombotic event (deep vein thrombosis); other possibly or probably drug-related SAEs included dehydration, cardiogenic pulmonary edema, cardiomyopathy, and gastrointestinal ulcer. Conclusions: Based on these preliminary data, this was a well-tolerated therapy but provided no obvious improvement in efficacy compared to historical controls. Study of ABT-510 in combination with other antiangiogenic or targeted agents may be reasonable, given the excellent safety profile of ABT-510. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories, AstraZeneca, Merck, Pfizer Abbott Laboratories, Celegene, Eli Lilly, Novartis Abbott Laboratories
Results of the PRIMER 1 randomized study comparing p values (P), p values plus 95% confidence intervals (P+CI), vs. p values plus 95% confidence intervals plus confidence levels (P+CI+CL) for optimizing physician interpretation of published clinical research
Authors: T. P. Shakespeare, V. Gebski, J. Tang, K. Lim
Journal: Journal of Clinical Oncology (2004)

6092 Background: Correct interpretation of research results depends on the amount of information presented. There is little evidence to suggest that 95% confidence intervals (CI) actually facilitate interpretation compared to P values alone (P), and we have suggested that confidence levels (CL) may better improve interpretation (Lancet 2001; 357: 1349–53). Our aim was to determine which method of result presentation enabled physicians to best interpret published research. Methods: Physicians in 2 hospitals were randomly allocated one of 3 questionnaires, each using a different method to present the results of the same 5 artificial studies. The study results were presented with P, P+CI or P+CI+CL depending on the questionnaire (available at www.PRIMERcollaboration.com). Physicians classified study results depending on statistical and clinical significance. Study scenarios and correct answers were based on published reports. Results: Median age of the 71 participants was 37 (25–67): 45% were specialists, 55% trainees. 41% had training in statistics. 75% read 1–5 journal articles / month, 18% more than 5. 85% were involved in research; 69% had first author publications. 32% were journal reviewers / editors. The mean number of correct interpretations (out of 10) for the 3 randomized arms was 6.9 (P+CI+CL), 5.5 (P+CI) and 5.0 (P) (test for trend p=0.01). Interpretation of study results containing P+CI+CL was better than results reported with P alone (p=0.01). P+CI did not improve interpretation compared to P alone (p=0.5). Conclusions: Providing information using P+CI+CL when presenting the results of clinical studies led to significantly better interpretation by physicians, who are researchers, journal readers, reviewers and editors. The results of our study suggest researchers and journal editors should provide confidence levels in addition to the policy of providing 95% CIs and P values. A second study, PRIMER 2, is underway and will provide further evidence for reporting published research. No significant financial relationships to disclose.
Characteristics and prognostic factors of primary peritoneal cancer
Authors: L. T. Chuang, S. J. Lee, Q. Shi, G. Ramaswamy
Journal: Journal of Clinical Oncology (2004)

5136 Background: To compare the disease characteristics of primary peritoneal cancer (PPC) with that of ovarian cancer, and to determine the prognostic factors of peritoneal cancer. Methods: Between 1994 and 2001, histology, tumor grade, CA125 levels, lymph node status, the site(s) of metastatic disease and the residual diseases were recorded for all womwn with ovarian and PPC. Univariate and multivariate analysis were used to evaluate the effects of these prognostic factors on the outcomes of patients with PPC. Results: One-hundred ninety-three patients were analyzed. Twelve percent of patients had ovarian tumors of low malignant potential (LMP), 74% of patients had primary epithelial carcinoma of the ovary and 14% patients had PPC. The mean age of patients with PPC were older than those with ovarian cancer (70 vs. 59, respectively). More PPC were associated with advanced stages (Stage III, IV) and higher grade (95% Grade 3) compared to ovarian cancer where 66% were Stage III, IV and 68% were Grade 3. The predominant histologic cell type of PPC were of serous cell type (94%). There were no significant differences in the status of lymph nodes between the PPC and ovarian cancer. However, there were significant differences in the incidence of diaphragmatic spread (83% vs 59%, p<0.001) between the PPC and ovarian cancer. Similarly, PPC were more likely to be associated with residual tumor size>1cm than ovarian cancer (54% vs. 23%, p<0.001). Using multivariate analysis, stage, grade, ascites, and lymph node status of PPC do not seem to affect the survival, whereas degree of residual disease appear to be the most important prognostic factor for patients with PPC. Conclusions: Patients with PPC are more likely to have advanced stage disease which is higher in grade and more aggressive. The PPC are more likely to have ascites, diaphragmatic involvement, and larger residual tumors than that of ovarian cancer. The status of residual tumor size appear to be significant prognostic factors in predicting long term survivals. Therefore, aggressive tumor debulking including diaphragmatic resection may be important to improve survival of patients with PPC. No significant financial relationships to disclose.
Abstract 15833: Imaging-Assisted versus Conventional Blind Technique for Venous Access in Patients Undergoing Catheter Ablation of AF Under Therapeutic Warfarin: Differences Between Femoral and Internal Jugular Vein Accesses
Authors: Pasquale Santangeli, Luigi Di Biase, John David Burkhardt, Rodney Horton, Rong Bai, Sanghamitra Mohanty, Agnes Pump, Chintan Trivedi, G. Joseph Gallinghouse, Javier Sanchez, Shane Bailey, Salwa Beheiry, Richard Hongo, Steven Hao, William R. Lewis, Andrea Natale
Journal: Circulation (2012)
Supplementing the Role of Primary Care Physicians
Authors: Richard L. Brown
Journal: JAMA Internal Medicine (2016)

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
Deliver us from evil
Authors: Imre Loefler
Journal: BMJ (2006)

Randomised controlled trials examining the effectiveness of prayer as a life saving intervention have become commonplace. All suffer from methodological shortcomings. What is prayer? Whom do the prayers address? How does one make sure that the person who claims to have prayed has done so? How does one know that the prayer did not pray for the opposite outcome? Are there people who can pray better than others? Does prayer come in doses? And if …
CD133 expression in glioblastoma recurring after radiation therapy.
Authors: T. Cenci, R. Pallini, M. Martini, L. R. Vitiani, N. Montano, F. Pierconti, R. De Maria, L. Larocca
Journal: Journal of Clinical Oncology (2010)

2028 Background: Experimental data suggest that glioblastoma cells expressing the stem cell marker CD133 play a major role in radiochemoresistance and tumor aggressiveness. To date, there is no clinical evidence that the fraction of CD133+ cells in glioblastoma recurring after radiochemotherapy may be relevant for prognosis. Methods: Using immunohistochemistry, we assessed the expression of the stem cell marker CD133 in 37 glioblastoma tumors at first diagnosis and at recurrence after adjuvant radiochemotherapy. To rule out endothelial precursor cells, the tumor specimens were also assayed with anti-CD34 immunohistochemistry. To dissect putative neural stem cells embedded in the tumor tissue, we assessed CD133+/CD45-/CD34- cells isolated by FACS sorting for tumor-specific chromosomal aberrations using interphase fluorescence in situ hybridization. Results: We found that in recurrent glioblastoma the percentage of CD133+ cells was increased by 2 folds in average as compared with tumors at first diagnosis, though in some instances CD133 expression increased up to 10-20 folds. Endothelial precursors barely contributed to the CD133+ cell population. Unexpectedly, the increase of CD133 expression significantly associated with longer survival after tumor recurrence. Analysis of tumor-specific chromosomal aberrations revealed that the CD133+ cell compartment of recurrent glioblastoma is composed both by cancer stem cells and by non-tumoral neural stem cells. The latter cells represent 20 to 60 percent of the CD133+ cell population and their relative amount favorably affects survival of patients with recurrent glioblastoma. Conclusions: Our data suggest that CD133+ neural cells migrating from surrounding brain towards the tumor may exert an antitumorigenic effect. No significant financial relationships to disclose.
Microsatellite instability (MSI) and loss of heterozigocity (LOH) in the peripheral blood mononuclear cells (PBMC) of breast cancer (BC) patients receiving systemic chemotherapy
Authors: A. Del Giglio, F. L. A. Fonseca, A. Santana, M. A. S. Pinhal, I. Bendit, L. Megale, V. Arias
Journal: Journal of Clinical Oncology (2004)

9628 Background: Despite the consistent improvement in overall survival afforded by systemic adjuvant chemotherapy, about 1% of Breast Cancer (BC) patients develop secondary leukemias and/or myelodisplasia probably as a consequence of the genotoxic effects of this type of treatment. Methods: In order to evaluate if systemic chemotherapy could produce microsatelite instability (MSI), we studied 119 sequential blood samples from 30 previously untreated BC patients, collected at every three months intervals, before, during and after receiving systemic chemotherapy. After PCR amplification of the extracted DNA with specific primers for 6 microsatelite loci (BAT-26, BAT-40, MFD-28, MFD-41, TP53, PCR15.1, tp53ALU), the PCR products were denatured, subjected to SSCP and for microssatelite instability (MSI) and loss of heterozigocity (LOH). We also evaluated the expression of PCNA, hMLH1, hPMS1, hPMS2, hMSH2 and P-53 proteins in the PBMC by immunocytochemistry. Results: We observed MSI in 40 of the 119 samples and 27 out of 30 patients had MSI observed in at least one of their collected samples. We observed appearance of LOH at the PCR15.1 locus in 6 patients. We observed a significant correlation between the number of MSI events per sample and the use of chemotherapy ( p = 0.005) specially if it contained alquilating agents (p < 0.0001) . We also observed an inverse correlation between the number of MSI events per sample and the percentage of positive cells for MSH2 by immunocytochemistry (p = 0,0001). The percentage of positive MSH2 cells by immunocytochemistry was inversely correlated with the use of chemotherapy regimens containing alquilating agents (p = 0.019). Conclusions: We conclude that alquilating agent chemotherapy may induce MSI and LOH in PBMC from BC patients possibly through chemotherapy induced decrease in the expression of MSH2. These findings may be related to the generation of secondary leukemias and may also contribute to the intensification of the genetic instability of tumors and further resistance to treatment. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration FAPESP
Gene expression profiling in germ cell tumors
Authors: C. Pan, M. J. Brames, L. Debrolecki, C.-W. Lee, J. Huang, R. Hickey, L. Einhorn
Journal: Journal of Clinical Oncology (2004)

4522 Background: Germ cell tumors (GCT) are highly curable. Nevertheless, some patients relapse because of persistent tumor cells. Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry, a proteomic technology, can detect tumor-associated proteins and diagnose cancer based on the proteomic profiles of serum. We performed this study to detect serum tumor-associated proteins with SELDI-TOF and identify patients with viable tumor cells post GCT chemotherapy. Our long-term goal is to differentiate curable versus persistent tumor after chemotherapy. An additional goal is to identify those bio-markers associated with resistance to chemotherapy. Methods: SELDI-TOF analysis of serum was performed to determine the proteomic patterns. The training cohort included patients with active GCT and patients who were disease-free for more than 2 years (NED). Based on the proteomic patterns derived from the training cohort, a prediction system will be developed. The subsequent test cohort will include patients with masked disease status. It will be used to validate the accuracy of the prediction of disease status from the training cohort. Results: We plan to enroll 50 patients (25 NED, 25 active GCT) in the training cohort. Thus far, SELDI-TOF analysis has been performed in 20 patients from the training cohort (13 NED, and 7 GCT). Detail data analysis has been performed on 9 samples (5 NED, and 4 GCT). After baseline subtraction and noise reduction, total 2700 significant peaks were selected out of 56253 points. Nineteen peaks were found to differentiate patients with or without GCT when the absolute t-test value was set at 4. The proteomic patterns were highly homogenous in each group, but significantly different between the active GCT and NED groups. Conclusions: SELDI-TOF has the potential to differentiate patients with or without active GCT. It may be possible to identify those patients with residual disease after chemotherapy and better determine their subsequent therapy. No significant financial relationships to disclose.
BCIRG 007: Randomized phase III trial of trastuzumab plus docetaxel with or without carboplatin first line in HER2 positive metastatic breast cancer (MBC)
Authors: J. F. Forbes, T. Pienkowski, V. Valero, W. Eiermann, G. Von Minckwitz, M. Martin, M. Smylie, J. M. Crown, N. Noel, M. Pegram
Journal: Journal of Clinical Oncology (2006)

LBA516 Background: Based on preclinical synergism between docetaxel (T), carboplatin (C) and trastuzumab (H), BCIRG conducted a phase III trial for women with HER2+ MBC to evaluate efficacy and safety of H in combination with T or TC. Methods: 263 patients (pts) with HER2 FISH+ MBC were randomized to TH, (H with T 100 mg/m 2 ) or TCH, (H with T 75 mg/m 2 and C AUC=6). Chemo was given q3 wks for 8 cycles with wkly H at 2 mg/kg (loading dose of 4 mg/kg), followed by H q3 wks at 6 mg/kg until progression. Pts were stratified by centre and prior (neo) adjuvant taxane chemotherapy. Primary endpoint was TTP with 80% power (0.05 significance) to detect a 50% improvement in median TTP between the 2 arms. Secondary endpoints include overall survival, response rate, duration of response (DR), clinical benefit (CB) and safety. Results: 131 pts were treated in each arm. Pt characteristics were well balanced in both groups. Importantly, only 52% of pts received C at the protocol specified dose (RDI &gt; 0.9). Efficacy analysis was conducted at 204 events. There was no significant difference between TH and TCH in median TTP (11.1 vs 10.4 mos, p = 0.57), ORR (73% in both arms), DR (10.7 vs 9.4 mos) and CB (67% in both arms). The most common gr 3/4 toxicities were: infection (44% vs 30%), neutropenic infection (22% vs 12%), thrombocytopenia (2% vs 15%), febrile neutropenia (12% vs 13%) asthenia (5% vs 12%), anemia (5% vs 11%), and diarrhea (2% vs 9%). Two pts died (1.5%) due to sepsis in TCH. Absolute LVEF decline &gt; 15% were seen in 5.5% vs 6.7% of pts. One pt (0.8%) had a symptomatic CHF in TH arm Conclusions: The already effective TH regimen does not benefit from the addition of C, when the T dose in TH is 100 mg/m 2 and 75 mg/m 2 in TCH, in women with HER2+ MBC. No significant financial relationships to disclose.
Contrast-Enhanced Ultrasound for the Characterization of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma
Authors: Guang-Jian Liu, Wei Wang, Ming-De Lu, Xiao-Yan Xie, Hui-Xiong Xu, Zuo-Feng Xu, Li-Da Chen, Zhu Wang, Jin-Yu Liang, Yang Huang, Wei Li, Jin-Ya Liu
Journal: Liver Cancer (2015)

The ability of contrast-enhanced ultrasound (CEUS) to differentiate between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is still controversial. We reviewed the CEUS imaging of 819 patients (HCC=546, ICC=273) with an established pathological diagnosis. The enhancement patterns of lesions and the diagnostic performance of CEUS were analyzed.Arterial hyperenhancement followed by washout was observed in 92.3% (504/546) of the HCC lesions and 85.7% (234/273) of the ICC lesions on CEUS (p<0.05). Additionally, the ICCs presented contrast washout much earlier than the HCCs, with an average time of 27.5 seconds after injecting the contrast agent compared with 70.1 seconds for the HCCs (p<0.05). Peripheral rim-like enhancement was observed in 68.5% (187/273) of the ICCs, which was significantly more common than that in the HCCs (2.0%, 11/546) (p<0.05). When using arterial hyperenhancement with a washout phase later than 43 seconds after injecting the contrast agent and with no peripheral rim-like enhancement as the diagnostic criteria for HCC ≤5 cm in diameter, the area under the curve was 0.808, with 64.1% sensitivity, 97.4% specificity and 73.6% accuracy.Although ICC may show the typical enhancement pattern of HCC on CEUS, peripheral rim-like enhancement and quick contrast washout show high efficiency in the differentiation of HCC from ICC.