tbuckley/cabot-search huggingface dataset:
Prediction of survival in patients with epithelial ovarian cancer based on the timing and rate of normalization of CA125 levels during primary chemotherapy
Authors: K. S. Matthews, R. P. Rocconi, M. Kemper, K. E. Hoskins, W. K. Huh, W. Wang, J. M. Straughn
Journal: Journal of Clinical Oncology (2007)

5585 Objective: CA125 is the tumor marker used to evaluate response to chemotherapy in patients with epithelial ovarian cancer (EOC). The aim of this study was to determine if the timing of normalization or percent decrease in CA125 levels during primary chemotherapy could predict survival. Methods: Patients treated at our institution for EOC with primary taxane/platinum-based chemotherapy for 6 cycles between 1996 and 2005 were eligible. Patient demographics, chemotherapy administration, CA125 levels, and survival outcomes were abstracted. Progression-free- survival (PFS), overall survival (OS), and platinum sensitivity (&gt; 6 months from chemotherapy completion) were compared to CA125 levels during primary therapy. Baseline levels, change over time, and timing of CA125 normalization were calculated. Analyses were performed using Kaplan-Meier method and compared using the log-rank test, Chi-square test and Fischer’s exact test. Results: 269 patients with EOC were identified. When stratified by which cycle of chemotherapy achieved normalization, PFS ranged from 25 months at 1st cycle to 4 months at 6th cycle (p&lt; 0.001). OS showed a similar benefit from 74 months at 1st cycle to 22 months at 6th cycle (p&lt;0.001). Platinum sensitivity improved from 23% (normal CA125 after 6th cycle) to 72% (normal CA125 after 1st cycle) (p=0.003). Patients with normalization after the 3rd cycle or sooner compared to patients with normalization after the 4th cycle demonstrated improved PFS (19 vs. 6 months; p&lt;0.001), OS (48 vs. 27 months; p=0.001) and platinum sensitivity (78 vs. 22%; p&lt;0.001). Linear regression models of the slope of the decline of CA125 levels correlated with PFS (p=0.03); however, the models failed to predict an OS advantage. Conclusion: Earlier normalization of CA125 levels during primary chemotherapy for EOC predicts improvement in platinum sensitivity, PFS, and OS. This data provides prognostic information that may influence future decisions regarding chemotherapy. No significant financial relationships to disclose.
Phase II Study Of The c-MET Inhibitor ARQ 197 (Tivantinib) In Patients With Relapsed Or Relapsed/Refractory Multiple Myeloma (RRMM)
Authors: Robert Z. Orlowski, Shadia Zaman, Sheeba K. Thomas, Raymond Alexanian, Jatin J. Shah, Donna M. Weber, Michael Wang, Ashley N. Holloway, Veerabhadran Baladandayuthapani, Heather Yan Lin, Min Fu, Christine M. Stellrecht, Claudia Morales de Partovi, Varsha Gandhi
Journal: Blood (2013)
Comparison of 21-gene recurrence score (RS) in African-American (AA) and Caucasian (C) patients with hormone receptor (HR)-positive early-stage breast cancer.
Authors: K. M. Davis, A. B. Zelnak, S. Murali, D. Senior-Crosby, S. Gabram-Mendola, G. W. Carlson, W. C. Wood, C. Wang, T. M. Styblo, R. O'Regan
Journal: Journal of Clinical Oncology (2010)

557 Background: AA patients have a worse outcome from breast cancer than their C counterparts, which is partly explained by their propensity to develop triple negative breast cancers. Additionally, we (May SABCS 2008) and others (Sparano SABCS 2009) have demonstrated that AA patients have a significantly worse outcome than C patients from hormone receptor (HR)-positive early-stage breast cancers. Our hypothesis was that AA patients are more likely to develop breast cancers that are intrinsically resistant to endocrine agents (high risk RS ≥ 31, luminal B cancers) and less likely to develop hormone-sensitive (low/intermediate RS ≤ 30, luminal A cancers), compared to C patients. Methods: Patients with early-stage breast cancer in whom RS was sent from 4/2005 through 12/2009 were identified from a University and County Hospital. The analysis was limited to patients with HR-positive, HER2-negative, stage 1, 2a and 2b breast cancers. Results: We identified 270 patients who met the above criteria of whom 55 (20%) were AA and 215 (80%) were C. There were differences in stage between AA and C: stage 1 53% AA, 73% C; stage 2a 36% AA, 16% C; and stage 2b 11% AA, 11% C. Overall, there was no difference in the distribution of RS risk based on race: low risk (RS ≤ 18) 49% AA, 53% C; intermediate risk (RS ≥ 19, ≤ 30) 36% AA, 34% C; high risk (RS ≥ 31) 15% AA, 13% C (p = 0.86). There was no significant association between race and RS divided into low/intermediate risk (hormone- sensitive) and high risk (hormone-resistant; p = 0.7). Logistic regression models including race, stage and year of birth as variables also failed to demonstrate any significant association between race and RS risk. Conclusions: This analysis demonstrates no difference in RS risk between AA and C diagnosed with early stage HR-positive breast cancer. This suggests that the disparate outcomes noted for AA compared to C with HR- positive early-stage breast cancer can not be explained by an increase in hormone-resistant cancers in AA. The disparity could be explained by decreased compliance and/or differences in metabolism of endocrine agents and future research should focus on these areas. No significant financial relationships to disclose.
Evaluation of tyrosinase mRNA as a tumor marker in the blood of melanoma patients.
Authors: F A Jung, A C Buzaid, M I Ross, K V Woods, J J Lee, M Albitar, E A Grimm
Journal: Journal of Clinical Oncology (1997)

The value of tyrosinase messenger RNA (mRNA) detection in the peripheral blood by reverse-transcription polymerase chain reaction (RT-PCR) as a melanoma marker remains controversial. The purpose of this study was to compare the sensitivities of two different blood processing techniques for tyrosinase mRNA detection and evaluate its potential clinical value.A total of 50 patients with progressive stage IV melanoma was studied. Two blood processing methods were used: RNA extraction from the whole blood and RNA extraction from density gradient-isolated peripheral-blood mononuclear cells (PBMC). The RNA samples were tested with a sensitive nested-primer RT-PCR assay. RT-PCR results were also correlated with serum lactate dehydrogenase (LDH), treatment status, and presence of visceral versus nonvisceral metastases.Thirteen (26%) of the density gradient and five (10%) of the whole blood processed samples were PCR positive (P = .011). Serum LDH levels were found to be significantly higher in PCR-positive PBMC-processed patients (P = .015). There was no significant difference in the detection rates between visceral versus nonvisceral metastases or between prior treatment versus no prior treatment.Using a density gradient method to process the blood samples resulted in a higher detection rate of tyrosinase mRNA than extracting the RNA from the whole blood. However, the relatively low sensitivity in patients with disseminated and progressive disease compared with other reports suggests that tyrosinase mRNA may be of limited value in the management of malignant melanoma.
A prognositc index predicts outcome following gemcitabine for patients with metastatic pancreatic cancer
Authors: A. Sawaki, N. Mizuno, K. Takahashi, T. Nakamura, M. Tajika, H. Kawai, Y. Kanemitsu, A. A. S. Salem, K. Yamao
Journal: Journal of Clinical Oncology (2005)

4119 Background: Chemotherapy with gemcitabine(GEM) has been shown to be an effective agent in metastatic pancreatic cancer(MPC) with improvement of both quality of life and survival. While median survival time of MPC patients treated with GEM is reported to be about 5 months, some of them live longer than median time and others do much shorter. Methods: To determine the outcome of patients with MPC treated with GEM and to identify factors that predict treatment outcome, retrospective study was preformed on patients with MPC who received GEM in a dose of 1000mg/m2 weekly×3 followed by 1week rest at our hospital between April 2001 and October 2004. Data regarding patient factors, tumor factors obtained by computed tomography and survival data were collected. Sixty-six consecutive patients were identified and they were pathologically diagnosed as adenocarcinoma without prior chemotherapy or surgery. Results: The median age was 60 years (range 36–78 years), 60.6% were male and 39.4% were female. Multivariate analysis showed that ECOG (Eastern Cooperative Oncology Group) performance status (p=0.046), primary tumor location (head, body and tail) (p=0.017) and C-reactive protein (p=0.002) were important independent predictive factors. A prognostic index was derived from these factors. The prognostic score was calculated using the formula of prognostic score=(1 if PS=0 or 1, and 2 if PS=2 and 5 if PS=3)+(3 if primary site at head, 1 if body or tail)+(1 if CRP<1, 6 if CRP>3, 3 if others). According to the calculated score, we divided them into three groups (class1; score=3 or 4, class3; score>8, class2: all others) and median survivals were 265, 155, 65 days for class 1–3, respectively (265 vs 155 vs 65; p<0.0001). The internal validated c-index (ROC area under the curve) of this model was 0.711. Conclusions: These classifications are valid when applied to patients with MPC. Patients in class 1 have good prognosis, class 2 are likely to benefit for GEM and should be considered for trials that aim to improve their survival. Class 3 patients are unlikely to benefit from GEM. No significant financial relationships to disclose.
Erratum: Corrigendum: Regulating anxiety with extrasynaptic inhibition
Authors: Paolo Botta, Lynda Demmou, Yu Kasugai, Milica Markovic, Chun Xu, Jonathan P Fadok, Tingjia Lu, Michael M Poe, Li Xu, James M Cook, Uwe Rudolph, Pankaj Sah, Francesco Ferraguti, Andreas Lüthi
Journal: Nature Neuroscience (2015)
Final results of a phase Ib trial of PR104, a pre-prodrug of the bioreductive prodrug PR104A, in combination with gemcitabine (G) or docetaxel (D) in patients with advanced solid tumors.
Authors: M. B. Jameson, M. J. McKeage, R. K. Ramanathan, J. Rajendran, Y. Gu, W. R. Wilson, T. J. Melink, N. S. Tchekmedyian
Journal: Journal of Clinical Oncology (2010)

2554 Background: PR104 is a nitrogen mustard pre-prodrug activated by hypoxia or the reductase AKR-1C3. When activated, PR104 exerts cytotoxicity through DNA crosslinking. Preclinical studies support combining PR104 with G or D. The MTD of single agent Q3wk PR104 is 1100 mg/m2 with dose-limiting toxicity (DLT) of neutropenia. Methods: Patients (pts) for which treatment with single agent G or D was considered reasonable were eligible. PR104 was combined with either G (800 mg/m2) or D (60 or 75 mg/m2) in 4 separate groups. Grp A received PR104 + G on days 1 and 8; Grp B received PR104 + D (60 mg/m2) on day 1; Grp C received PR104 + D (60 mg/m2) on day 1 with GCSF; Grp D received PR104 + D (75 mg/m2) on day 1 with GCSF. All groups were retreated on a 21 day cycle. Plasma pharmacokinetics was assessed with cycle 1. At selected sites tumor hypoxia was evaluated with F18-fluoro-misonidazole positron emission tomography (FMISO-PET). Results: 42 pts: 23 F/19 M; median age 61 (range 27-87); median of 2 prior chemotherapy regimens (range 0-3); NSCLC (10 pts), pancreatic and prostate (4 pts each), sarcoma and melanoma (3 pts each), and other solid tumors (18 pts) received a median of 3 treatment cycles (range 1-23). Grps A (6 pts) and B (6 pts), defined MTDs for PR104 at ≤200 mg/m2 with myelotoxicity as DLT. Grp C (21 pts) defined an MTD of 770 mg/m2 for PR104. The DLTs in 2/6 pts at 1,100 mg/m2 were grade 4 thrombocytopenia and grade 3 fatigue. Two pts had a partial response (nasopharyngeal and H&N cancer) and 10 pts (5 with NSCLC) had stable disease (≥6 cycles). Grp D (6 pts restricted to ≤1 prior chemotherapy) received PR104 at 770 mg/m2 + D at 75 mg/m2 with GCSF, no DLT were observed. PR104 was rapidly converted to the alcohol PR104A and further metabolized to the glucuronide PR104G and the cytotoxic hydroxylamine PR104H. Tumor hypoxia was detectable in 11/17 baseline scans. Conclusions: The MTD ofPR104 with G or D in the absence of concomitant GCSF is ≤200 mg/m2. With GCSF, PR104 can be administered at a dose of 770 mg/m2 (70% of its single agent MTD) with D (60 or 75 mg/m2). A randomized phase II trial of PR104 + D (60mg/m2) with GCSF was initiated in relapsed NSCLC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Proacta Proacta Proacta Proacta
Oligoclonal TCRBV Gene Usage in B-Cell Chronic Lymphocytic Leukemia: Major Perturbations Are Preferentially Seen Within the CD4 T-Cell Subset
Authors: Mohammad-Reza Rezvany, Mahmood Jeddi-Tehrani, Anders Österborg, Eva Kimby, Hans Wigzell, Håkan Mellstedt
Journal: Blood (1999)
SNPs associated with the genetic predisposition to develop therapy-related acute myelogenous leukemia after chemotherapy for breast cancer
Authors: V. Guillem, M. Mata, A. Lluch, M. Gonzalez, J. Esteve, J. Nomdedeu, M. Calasanz, A. Cervantes, I. Chirivella, M. Tormo
Journal: Journal of Clinical Oncology (2006)

8536 Background: t-AML is a syndrome occurring after exposure to chemo or radiotherapy. Since for similar treatments only some patients ends developing a secondary leukemia, it has been proposed a genetic predisposition associated to this syndrome. Methods: To analyse single nucleotide polymorphisms (SNPs) on genes that could be involved on risk of developing t-AML by means of RFLP and SNP genome screening using high density microarrays .Two groups of individuals were genotyped: Group A, composed by patients that develop t-AML after chemotherapy for breast cancer (BC) and Group B (control), formed by chemotherapy treated BC patients that after a period of more than 10 years have not developed t-AML. We have studied 12 polymorphisms on genes from drug detoxification pathways (NOQ1, GSTP1), DNA repair (XPC[3 ], XRCC1[2 ], NBS1, ERCC5 and XRCC3) and DNA synthesis (MTHFR[2 ]), in which the nucleotide change implies a change in the protein sequence (n A =16, n B =18) . Alternatively, for each patient, more than 10.000 SNPs were genotyped by means of of high density microarrays (Affymetrix) (n A =12, n B =18). The alele frequencies for each SNP between two groups were compared. Results: In RFLP study, we observe two SNPs on MTHFR gene displaying remarkably different allele frequencies between BC patients (Table). In microarray study, we found 12 SNPs with differences of allele frequency higher that 45% between A and B groups, located 6 on chromosome 8. Conclusions: The results suggest that the MHFTR gene is a candidate for being studied by its possible relation with the genetic predisposition to develop t-AML after BC treatment although its functional implication with the disease must still be elucidated. Moreover, data from SNP arrays suggest that the genome regions marked by those 12 SNPs, specially those on chromosome 8, are candidate for being studied by its possible relation with the genetic predisposition to develop t-AML after BC treatment. Financed by FIS G03/008. [Table: see text] No significant financial relationships to disclose.
Health care disparity: An analysis of breast, colon, and lung cancer
Authors: S. Dubey, A. Griffin, J. Hwang
Journal: Journal of Clinical Oncology (2009)

6579 Background: Lung cancer patients are associated with feeling of guilt about their disease (Schmidt ASCO 2006) and less likely to be referred to specialists (Wassenaar ASCO 2006). They are also commonly affected by smoking related comorbidities. A study was undertaken to evaluate whether treatment differences between lung and other cancers exist. Methods: Public access data for the year 2005 from the National Cancer Data Base (NCDB) was analyzed. Treatment data were categorized by institution (teaching/research [TR] versus community cancer center [CC]) and tumor type (non-small cell lung cancer-NSCLC, breast, colon cancer). Descriptive analysis was performed with student T tests for proportions. Results: The analysis included 18,960 NSCLC patients from a CC and 33,924 from a TR. More patients at TR than CC had surgery: Stage I 65% vs 52% (p &lt; 0.001), Stage II 35% vs 22% (p &lt; 0.001), respectively. The frequency of chemoradiation for stage I and II was higher in CC than TR: stage I 6% vs 3% (p = 0.10), stage II 19% vs 9% (p = 0.004). The frequency of no first course treatment at initial presentation at CC and TR were the following: stage I 15% vs 6%, stage II 18% vs 8%, stage III 21% vs 19%, stage IV 30% vs 24%. For breast and colon cancer, no major differences in no first course treatments were seen between TR and CC in a stage based analysis. More patients with NSCLC (21.2%) did not receive first course treatment in comparison to breast (3.4%, p &lt; 0.001) or colon cancer (7.8%, p &lt; 0.001). These differences were maintained in stage based analysis of the three tumor types. Conclusions: NSCLC patients are at higher risk of not receiving treatment as opposed to those with breast and colon cancer. While medical comorbidities in lung cancer patients may affect these treatment decisions, we noted a higher incidence of no first course treatment in CC than TR centers. For stage I and II, the frequency of no first course treatment in a CC was twice that of a TR. Such institution based differences were not noted in breast and colon cancer. No significant financial relationships to disclose.
Neoadjuvant immunotherapy for prostate cancer with GM-CSF and tumor infiltration by antigen presenting cells
Authors: L. Fong, V. Dao, S. O'Brien, J. Simko, V. K. Weinberg, C. Ryan, J. E. Rosenberg, A. M. Lin, P. Carroll, E. J. Small
Journal: Journal of Clinical Oncology (2008)

3063 Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth factor for antigen presenting cells that may enhance anti-tumor immune responses. Although this cytokine is being evaluated in immunotherapy trials for different malignancies, the impact of GM-CSF dose and schedule has not been directly addressed. Because systemic GM-CSF could potentiate anti-tumor immunity by enhancing presentation of endogenous tumor antigens, we examined whether increasing duration of GM-CSF treatment prior to radical prostatectomy could alter the composition of antigen presenting cells within the prostate tissue. Methods: A phase I trial in patients with localized prostate cancer was performed in subjects who were planned to undergo radical prostatectomy (RP). Two cohorts of 6 patients were sequentially accrued and treated with either 2 weeks or 3 weeks of daily GM-CSF (sargramostim, Bayer) 250 mg/m2/d SC. Patients were monitored for toxicity as well as for changes in circulating immune cells. RP tissues were assessed for immune cells by flow cytometry or immunohistochemistry (IHC) and digital slide scanning. In addition, IHC was also performed on RPs from untreated control Gleason grade- matched patients. Results: 12 patients were treated with neoadjuvant GM-CSF for either 2 weeks or 3 weeks. While significant leukocytosis was observed with treatment, no dose-limiting toxicities were encountered. As expected, circulating monocytes and dendritic cells (DC) were expanded following treatment. Compared to RPs from 11 untreated control patients, there was an increase in prostate-resident CD1a+ interstitial DC (Kruskal-Wallis test: p = 0.04). The increase was most pronounced in the 3-week treatment cohort. Moreover, tumor-resident DC expressed higher levels of the activation markers CD83 and 86 compared to DC residing in adjacent normal prostate and benign prostatic hypertrophy tissue. Conclusions: Systemically administered neoadjuvant GM-CSF can enhance the frequency of DC in prostate cancer. These effects appear to be dose dependent as they were most pronounced with 3 weeks of treatment. The composition of resident DC and monocytes also differs between malignant, benign, and hypertrophic prostate tissue. No significant financial relationships to disclose.
Phase II trial of 21-day regimen of irinotecan and carboplatin for chemonaive or relapsed small-cell lung cancer: Long-term survival
Authors: G. Q. Chen, M. Huynh, L. Fehrenbacher, A. M. Davies, H. West, P. Gordon, M. Pan, M. Russin, P. N. Lara, D. R. Gandara, D. H. Lau
Journal: Journal of Clinical Oncology (2008)

19009 Background: The regimen of irinotecan and platinum is a promising treatment for metastatic small-cell lung cancer (SCLC) (Noda et al. NEJM, 346:85, 2002). We conducted a multi-institution trial to evaluate the efficacy and toxicity of a novel 21-day schedule of irinotecan and carboplatin in chemonaive patients with extensive SCLC (arm A) and previously chemotherapy-treated patients with relapsed SCLC (arm B). We are updating long-term survival data 5 years after initiation of the trial. Methods: According to a 2-stage phase II design, 80 patients (40 in arm A and 40 in arm B) have been enrolled with the following characteristics: male/female, 39/41; median age, 65 years; performance status (PS), 0–1 (85%), 2 (15%). Dosing schemas were based on population-based maximum tolerated doses determined in a previous intrapatient dose-escalation trial at our institution (Wild et al. Oncology 17:11–16, 2003). Chemonaive patients with extensive disease (arm A) were treated with irinotecan 200 mg/m2 and carboplatin AUC of 5; while patients with previously chemotherapy-treated and relapsed disease (arm B) received irinotecan 150 mg/m2 and carboplatin AUC of 5, every 21 days for 6 cycles. Results: The most common grade 3/4 toxicities are presented in the Table. Among 69 assessable patients, response rates of 69% and 49% were observed for arm A and arm B, respectively. By intent-to-treat Kaplan-Meier analysis, the median survival is 10 months for both Arm A and B. 1-year and 2-year survivals are 35.0% and 12.5% for Arm A and 30.3% and 11.4% for Arm B, respectively. Conclusions: This 21-day regimen of irinotecan and carboplatin is feasible and particularly promising for treatment of relapsed SCLC. Growth factor support with G-CSF is recommended with the regimen. (Supported by Pfizer Inc. and NCI K24CA10014) Toxicity Arm A (%) N = 37 Arm B (%) N = 33 Total (%) N = 70 Neutropenia 19 (51) 16 (48) 35 (50) Thrombocytopenia 8 (22) 5 (15) 13 (19) Anemia 4 (11) 4 (12) 8 (11) Diarrhea 9 (24) 5 (15) 14 (20) Nausea/emesis 3 (8) 5 (15) 8 (11) Treatment death 2 (5) 1 (3) 3 (4) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology
Learn fast by using<i>BJSM's</i>multiple choice questions
Authors: Babette M Pluim
Journal: British Journal of Sports Medicine (2015)

BJSM Education offers four types of interactive online modules to improve your knowledge and expertise.

If you just want a quick bite of knowledge, go to our Image Quizzes at http://bjsm.bmj.com/site/image-quiz. The site gives you the opportunity to study an image of a real-life case, identify the most likely diagnosis and read up on the subject. We have cases on injuries of the ankle, lower leg, knee, upper leg, hip, shoulder and skin, but we are looking for much more! …