tbuckley/cabot-search huggingface dataset:
Paclitaxel-carboplatin (P-C) regimen for metastatic breast cancer (MBC): Single-institution retrospective evaluation.
Authors: M. Zambetti, G. Goisis, A. Moliterni, A. Marchianò, D. Scaramuzza, M. L. Carcangiu, G. Saibene, G. Mariani, G. V. Bianchi, P. Valagussa, L. Gianni
Journal: Journal of Clinical Oncology (2011)

1113 Background: Clinical data on P-C activity in MBC across molecular subgroups are limited. Methods: The present retrospective evaluation reports on the efficacy of P-C regimen delivered to 114 consecutive patients presenting with the following characteristics: previous 0-2 CT lines for MBC; evaluable or measurable disease; PS 0-1; assessment of ER, PgR and HER2 status. Previous chemotherapy with taxanes were given to 52% and with anthracyclines to 91% of women (adiuvant and/ or metastatic setting). Selected doses were: P, 80 mg/m2; CBDCA, AUC=2, d 1 and 8, q3 wks. The median number of administered cycles was 6 (2-12). 22 of 31 HER2+ women were given concomitant trastuzumab (T). In the absence of progression after a minimum of 6 P-C cycles, 64 patients were given either endocrine therapy (35), or T (11), or other regimens (18). Recist criteria were independently assessed by three investigators. Results: 53 clinical responses (CR + PR) were observed (46%), and were more frequent when P-C was given as 1st and 2nd instead of 3rd line. Objective response (OR) rate was higher for soft tissue and visceral (56 and 46%) than for bone lesions (26%). Response rates according molecular subgroups are reported in the table. OR for HER2+ vs HER2-: 68 vs 39% (p=0.024) and for HR+ vs HR-: 44 vs 51% (p=0.62). Side effects were reported as G£1 in 58% and G3 in 12% of women. Ten patients (9%) discontinued treatment because of toxicity. Conclusions: Present results indicate: 1) clinical activity across molecular subgroups; 2) higher therapeutic efficacy among HER2+/ trastuzumab-treated patients, 3) good tolerability. HR+/HER2- HR+ /HER2+ HR-/HER2- HR-/HER2+ Pts (#) 60 19 23 12 OR (CR + PR) (%) 37 68 (+T=73) 43 67 (+T=73) PD (%) 37 21 43 17 TTP, median (mos) 8 14 5 14 2y TTP (%) 18 22 (+T=40) 10 17 (+T=18) OS, median (mos) 42 55 26 46 2y OS (%) 70 70 (+T=80) 50 61 (+T=67)
Modafinil for fatigue associated with docetaxel-based chemotherapy: A randomized controlled trial.
Authors: Elizabeth J. Hovey, Paul L. De Souza, Gavin M. Marx, Tal Rapke, Phillip Parente, Andrew Hill, Antonino Bonaventura, Antonio Michele, Paul Stanley Craft, Ehtesham A. Abdi, Andrew R. Lloyd
Journal: Journal of Clinical Oncology (2012)

e15152 Background: Docetaxel is the standard of care for castrate-resistant prostate cancer, but is associated with a high level of fatigue, limiting dosage and leading to premature withdrawal from therapy. Methods: A multicenter, randomized, double-blind, placebo-controlled, parallel group study in patients with metastatic prostate or breast cancer suffering significant chemotherapy-related fatigue whilst undergoing docetaxel-based chemotherapy. Patients were enrolled at the start of their 3 rd or subsequent cycles of docetaxel which was continued for up to four further cycles (defined here as ‘treatment periods’). Patients were randomized 2:1 to receive modafinil 200mg daily or placebo for 15 days during each treatment period. Fatigue was evaluated by the MD Anderson Symptom Inventory (MDASI). The primary endpoint was MDASI area under the curve (AUC) during the first 7 days of study medication for the first two treatment periods (possible range 0-70). Other validated tools were used to record disturbances in sleep, mood and functional status. Results: Eighty-three patients (65 with prostate cancer) were randomized and received at least one dose of study medication. The number of grade 3 or 4 adverse events (AEs) was 16/55 (29.1%) in the modafinil group and 5/28 (17.9%) in the placebo group. The toxicity profile was largely consistent with docetaxel-based chemotherapy and with previously reported AEs associated with modafinil use in the community; 11 AEs were possibly related to docetaxel; 1 to modafinil and 9 to neither treatment. Conclusions: Assessing and managing chemotherapy-related fatigue remains a major challenge. Despite not reaching the primary endpoint, there was a consistent trend towards improvement of chemotherapy-related fatigue in the modafinil arm. Further studies are needed to better address the significant symptom of docetaxel-related fatigue. Funding sanofi-aventis; Study ID NCT00917748. [Table: see text]
Blood Pressure and LV Remodeling Among American-Style Football Players
Authors: Jeffrey Lin, Francis Wang, Rory B. Weiner, James R. DeLuca, Meagan M. Wasfy, Brant Berkstresser, Gregory D. Lewis, Adolph M. Hutter, Michael H. Picard, Aaron L. Baggish
Journal: JACC. Cardiovascular imaging (2016)
Advanced well-differentiated/dedifferentiated liposarcomas: Role of chemotherapy and survival.
Authors: M. Toulmonde, A. Italiano, N. Penel, A. Cioffi, A. Le Cesne, N. Isambert, E. Bompas, F. Duffaud, A. Patrikidou, R. G. Maki, J. Coindre, J. Blay, B. Bui Nguyen
Journal: Journal of Clinical Oncology (2011)

10071 Background: Data regarding the role of systemic therapy in patients (pts) with advanced well-differentiated/dedifferentiated liposarcomas (WLPS/DDLPS) are limited. Methods: From 2000 to 2010, 166 pts with a confirmed diagnosis of WDLPS/DDLPS were referred to one of the 8 participating institutions, and their medical records reviewed. Results: Median age was 63 years (range 34-84). Thirty pts had WDLPS and 136 pts had DDLPS. Primary tumor sites were: retroperitoneum n=120 (73%), limb n=19 (11%), other n=27 (16%). 111 pts (67%) had metastatic disease (peritoneal sarcomatosis n=75; lung n=30, liver n=19, bone n=5) and 55 pts (33%) had locoregional unresectable disease. 27 pts (16%) had ≥ 2 metastatic sites. 103 pts (62%) received 1st line single agent chemotherapy. 131 pts (79%) received a 1st line anthracycline-containing regimen (doxorubicin n=64, doxorubicin + ifosfamide and/or dacarbazine: n=45, other: n=22). Non-anthracycline regimens were: metronomic cyclophosphamide or etoposide: n=17; trabectedin: n=4, others: n=14. RECIST objective response was observed in 18 pts (11%), all treated with anthracyclines. Response rate was higher in pts receiving combination chemotherapy: 17% vs 7%, p=0.03. 62 pts (37%) had stable disease > 6 months. Median progression-free survival (PFS) was 5.2 months (95% CI: 3.4-7.0). On multivariate analysis, performance status (PS) ≥ 2 was the sole factor significantly associated with poor PFS (Hazard ratio [HR]= 2.2; 95% CI 1.4–3.5; p<0.0001). 77 pts (46%) received further lines of systemic treatments (median: 1, range 1-5). Median overall survival (OS) was 15.4 months (95% CI: 10.7-20.1). On multivariate analysis, PS ≥2 (HR=2.1; 95% CI 1.1–3.9; p=0.026) and lymphopenia <1000/mm3 (HR= 2.2; 95% CI 1.2–3.9; p = 0.01) were the sole factors significantly associated with poor OS. Conclusions: Chemotherapy is associated with a non-progression rate of about 50% in pts with advanced WDLPS/DDLPS. Combination chemotherapy gives higher response rate than single agent but appears to have no impact on PFS or OS. OS of pts with advanced WDLPS/DDLPS is poor, even if visceral metastatic disease is less frequent than in other sarcomas. Best supportive care should be considered in pts with poor PS.
The efficacy and safety of degarelix, a GnRH receptor antagonist: A multicenter, randomized, maintenance dose-finding phase II study with Japanese prostate cancer patients.
Authors: S. Ozono, T. Ueda, S. Hoshi, A. Yamaguchi, H. Maeda, Y. Fukuyama, Y. Ohashi, T. Tsukamoto, S. Naito, H. Akaza
Journal: Journal of Clinical Oncology (2011)

154 Background: Degarelix, a GnRH receptor antagonist inducing rapid, profound and sustained suppression of serum testosterone levels, without testosterone surge, was evaluated in a phase II dose finding study in Japan. Methods: A total of 278 patients with adenocarcinoma of the prostate were randomized and 273 patients (any stage; median age, approx. 76 years; median testosterone, 4.46 ng/mL; median prostate-specific antigen (PSA) level, 22.8 ng/mL) received study treatment. Degarelix was administered subcutaneously at an initial dose of 240 mg followed by monthly maintenance doses of either 80 mg or 160 mg. The treatment continued for 12 months in the study. Results: The primary endpoint was the proportion of patients with testosterone suppression to castrate level of ≤0.5 ng/mL during 12 months treatment. Both dose regimens of 80 mg and 160 mg kept 94.5% and 95.2% of patients on castrate level respectively throughout the treatment period. At 3 days of treatment, approximately 99% of the patients reached the castrate level without testosterone surge. The percentage change in serum PSA reduction exceeded 76% at 4 weeks. The overall tumor response rates (proportion of patients with complete and partial responses) were from 77.4% to 90.8% across the groups. Eighteen patients (6.6%) withdrew from the study due to adverse events. The most common adverse events were injection site reactions; other adverse events included pyrexia, weight increased, hypertension and hot flush. Degarelix appeared well tolerated. Conclusions: With an initial dose of 240 mg followed by monthly maintenance doses of 80 mg or 160 mg, Degarelix resulted in a rapid profound and sustained testosterone suppression to castrate level and PSA reduction without testosterone surge for 12 months. Degarelix was well tolerated. The maintenance doses of 80 mg and 160 mg had similar efficacy and safety profiles. The study shows results similar to those from the degarelix pivotal phase III study (CS21). Assessment of risk-benefit would support the recommendation of the maintenance dose of 80 mg as a safe and effective monthly dose for the treatment of prostate cancer. [Table: see text]
Frequency, Characteristics, and Reversibility of Peripheral Neuropathy (PN) in the APEX Trial.
Authors: J.F. San Miguel, P. Richardson, P. Sonneveld, M. Schuster, D. Irwin, E. Stadtmauer, T. Facon, J. Harousseau, D. Ben-Yehuda, S. Lonial, H. Goldschmidt, D. Reece, J. Blade, M. Boccadoro, J. Cavenagh, W. Dalton, A. Boral, D. Schenkein, K. Anderson
Journal: Blood (2005)
A Doctor’s Prescription for Health Care Reform: The National Medical Association Tackles Disparities, Stigma, and the Status Quoby Rahn Kennedy Bailey, M.D., D.F.A.P.A. Bloomington, Ind., WestBow Press, 2013, 126 pp., $16.95 (paperback).
Authors: Felton Earls
Journal: American Journal of Psychiatry (2016)
Use of <i>TMPRSS2-ERG</i>gene rearrangement and quantitative <i>ERG</i> expression to predict clinical recurrence after radical prostatectomy.
Authors: S. M. Falzarano, C. Magi-Galluzzi, W. F. Novotny, T. Maddala, D. B. Cherbavaz, C. Millward, E. A. Klein
Journal: Journal of Clinical Oncology (2011)

4541 Background: The association of TMPRSS2-ERG fusions and ERG expression in prostate cancer (PC) with adverse clinical outcomes has been controversial, with mixed results in the literature. We conducted a study to test whether tumor-derived gene expression profiles, including the presence of TMPRSS2-ERG fusions and ERG gene expression, are associated with clinical recurrence (cR) after radical prostatectomy (RP). Methods: All patients with clinical stage T1/T2 prostate cancer treated with RP at CC from 1987 to 2004 were identified (n~2,600). A cohort sampling design was used to select 127 patients with cR and 374 patients without cR after RP. For each patient a primary Gleason pattern (GP) sample, secondary (or highest) GP sample, and an adjacent nontumor (NT) tissue sample were evaluated. Surgical Gleason Score (GS) and clinical data were centrally reviewed. RNA was extracted from 6 manually dissected 10 μm formalin-fixed paraffin-embedded sections obtained from RP specimens and expression of TMPRSS2-ERGa, TMPRSS2-ERGb, ERG and reference genes were quantified using RT-PCR. Times to cR, PSA recurrence, and PC death were analyzed using Cox PH regression. Results: Blocks from 441 patients were evaluable. Median F/U was 5.8 years. Patients were mostly Caucasian (83%), clinical stage T1 (66%), had baseline PSA <10 ng/mL (82%), and surgical Gleason score ≤7 (87%). 848 tumor samples and 410 nontumor samples were assessed. TMPRSS2-ERGa and/or TMPRSS2-ERGb fusions were present in 51.8% of tumor samples and 7.5% of nontumor samples. There was 89% concordance for TMPRSS2-ERG fusion status between the 2 tumor samples for each patient overall, and 82% concordance in the subset of patients for whom the two specimens were sampled from 2 distinct foci. We did not find an association between TMPRSS2-ERG a/b gene rearrangement or ERG expression with cR, PSA recurrence, PC death, or surgical GS (p > 0.2). Conclusions: This study was notable for the large number of cR events, use of a standardized quantitative assay, and rigorous central review of pathology and clinical data. We did not find an association of TMPRSS2-ERG gene rearrangements or ERG expression with aggressiveness of prostate cancer post RP.
Expression (Exp) of FIP200 and Rb in breast cancer (BreastCA) metastasis (met) to the brain.
Authors: N. Hashemi Sadraei, M. Burgett, M. S. Ahluwalia, R. Tipps, D. Khosla, R. Weil, A. Nowaki, R. Prayson, T. Shi, C. Gladson
Journal: Journal of Clinical Oncology (2011)

222 Background: BreastCA is the 2nd leading cause of cancer deaths in women in the US. Although the outcome for BreastCA with brain met remains poor, there is significant variation in overall survival (OS). Yet, there are no markers or models to predict OS. FIP200 regulates several pathways. In the nucleus, it inhibits cell proliferation by promoting Rb-1 and p21, and in the cytoplasm it promotes cell survival by inhibiting Pyk2 and regulating autophagy. It has been reported that FIP200 gene is deleted or mutated in 20% of primary BreastCAs, and its Exp is correlated with Rb1 levels. FIP200 Exp, its cellular localization, and gene alterations have not been examined in brain met of any cancer. Methods: Brain met tissues of 21 BreastCA patients (pts) biopsied in our institution between 8/2000 and 3/2010 were obtained and Exp of FIP200 and Rb1 were analyzed. Biopsies were selected based on tissue adequacy and prior diagnosis (Dx) of invasive intra-ductal BreastCA. Immunohistochemistry (IHC) was used to evaluate the localization and Exp levels of FIP200 and Rb1 which in turn were tested as predictors of OS. Genetic alterations in FIP200 and Rb1 were examined after DNA extraction. Results: Median time from Dx to met was 23 (range 0-245) months (mos), and median OS from Dx was 43 (range 6-264) mos. Nuclear Exp of Rb1 in &lt; 30% vs. ≥ 30% of cells were seen in 11 vs. 10 pts. Median OS was 39 (range 6-264) mos for Rb1 Exp &lt; 30% and 47 (range 20-190) mo for Rb1 Exp ≥ 30%. Nuclear Exp of FIP200 in &lt;20% vs. ≥ 20% of cells were seen in 13 vs. 8 pts. Median OS was 39 (range 6-264) mo for FIP200 nuclear Exp &lt;20% and 45 (range 43-122) mo for FIP200 Exp ≥ 20%. DNA analysis of 11 pts for copy number variations and loss of heterozygocity (LOH) showed no deletion mutations in FIP200 or Rb1, loss of p53 in 4 of 11, ErbB2 (Her-2) amplification in 4 of 11, and no EGFR gene mutations. Conclusions: The nuclear Exp of Rb1 in brain met from invasive intra-ductal BreastCA may be linked OS. An expanded study is underway to define whether nuclear FIP200 in &gt;20% of cells correlates with nuclear Rb and OS in BreastCA.
Correlation of FDG-PET-CT with Bone Marrow Aspiration and Biopsy at the Initial Staging in Follicular Lymphoma: Can We Omit Bone Marrow Biopsy in Some?
Authors: Manju Sengar, Hasmukh Jain, Venkatesh Rangarajan, Archi Agrawal, Hari Menon, Sridhar Epari, Tanuja Shet, Sumeet Gujral, Uma Dangi, Siddhartha Laskar, Nehal Khanna
Journal: Blood (2014)
BRAF and KRAS mutations in penile cancer and their correlation with clinical features.
Authors: C. M. Valverde, J. Hernandez-Losa, C. Ferrandiz-Pulido, R. Morales, C. Suarez, I. de Torres, C. Serrano, J. Carles
Journal: Journal of Clinical Oncology (2011)

221 Background: Penile cancer is a rare disease in developed countries. While surgery may be curative for patients with localized disease, for metastatic patients systemic chemotherapy may offer palliation with usually short-lived responses. Thus, new options in this setting are needed. Retrospective series have reported EGFR overexpression in more than 90% of the cases and also interesting results of EGFR directed therapies in these patients have been comunicated. The role of KRAS status or other molecular markers as prognostic or predictive factors remains unclear. The aim of this study was to determine the prevalence of BRAF and KRAS somatic mutations in penile cancer and their correlation with clinicopathologic features. Methods: We analyzed 28 samples collected from de archives of the Pathology Department at our institution from 1996 to 2009. The DNAs were extracted from FFPE blocks by Biorobot EZ1 following the manufacturer protocol of the EZ1-DNA Tissue kit (Qiagen). KRAS and BRAF mutations were amplified with specific primers, and sequenced by Sanger with Bigdye terminator v3.1 Cycle Sequencing Kit. Medical records were reviewed for clinical data. Results: No BRAF mutations were found, but we identified somatic missense mutations in the KRAS gene (all activating G12D mutations) in 6/27 samples (22%, one not evaluable). Median age at diagnosis (73 vs. 71), grade and histologic subtype did not differ between wt and mutated (mt) patients. There was a trend toward a more advanced stage at diagnosis in mt versus wt : 33 versus 47% stage I, 16 versus 9% stage II and 50 versus 38% stage III respectively. 2/6 mt patients died (due to other causes) as did 5/21 wt patients (3 of them because of disease progression). Conclusions: BRAF mutations seem not involved in the EGFR pathway in penile carcinomas. The prevalence of KRAS mutations was unexpectedly high in our series and mt patients tended to be diagnosed at a more advanced stage. Unfortunately, no correlation was found with other clinicopathologic features, including overall survival in our small series. These results suggest a role of KRAS mutation in the development of these carcinomas and support the importance to determine KRAS status in patients to be treated with anti-EGFR based therapies. No significant financial relationships to disclose.
A phase II study evaluating the toxicity and efficacy of single-agent temsorilmus (TEM) in chemotherapy-naive castration-resistant prostate cancer (CRPC): First report of suggested activity.
Authors: Chadi Nabhan, Kimberly Kruczek, Kathy Tolzien, Angel G. Galvez, Timothy M. Lestingi
Journal: Journal of Clinical Oncology (2012)

165 Background: PTEN tumor suppressor gene is mutated in CRPC allowing for downstream protein activation including mammalian target of rapamycin (m TOR) leading to tumor cell growth and survival. We investigated TEM; an mTOR inhibitor, in chemotherapy-naïve CRPC patients (pts). Methods: Eligible pts received TEM at 25 mg weekly until disease progression. Responses were assessed every 8 weeks and toxicity every 4 weeks using CTCAE v.3. Quality of life (QOL) data were collected every cycle using two previously validated scales. Primary end point: Clinical Benefit (CB) [sum of complete response (CR), partial response (PR), and stable disease (SD)]. Secondary end points: Toxicity, time to next treatment (TTNT), time to radiographic and PSA progression (TTP and TTP-PSA respectively), impact on QOL, and overall survival (OS) Results: To date, 18 pts have been enrolled. Median age was 75 (57–89) with Gleason ≥7 in 14 (77%), and median PSA 211.3 (10.8-1,449). Ten pts (55.5%) had bone and visceral disease. Median time on androgen deprivation therapy (ADT) was 60 months (17–240). Previous therapy included: surgery 3, brachytherapy 3, external radiation 5, ADT 7. All pts were evaluable for toxicity and 16 for response. Six pts (33%) were taken off study without progression (2 withdrew, 3 persitsant thrombocytopenia, 1 non-compliance). Biochemical response data was available for 15 pts (2 not evaluable, 1 refused), of which 4 (26%) had PSA decline and 1 (6%) had &gt;50% drop in PSA. TTP-PSA was 2 months (2-12). Sixteen pts were evaluable by RECIST; 2 PR and 9 SD for a CB of 69% (11 of 16). TTP or event (toxicity that took pts off study was an event) was 3 months (3–10) and TTNT was 4 months (2–11). With a median follow up of 18 months, 8 pts (44%) remain alive for a median OS of 13 months. Most commonly reported grade 3/4 toxicities: Thrombocytopenia (22%), hyperglycemia, hypophosphatemia, and fatigue (17% each), pneumonia and anemia (12% each). TEM did not impact QOL adversely without treatment-related mortality. Conclusions: TEM has activity in CRPC; some pts have CB without adverse impact on QOL. TEM should be further investigated in combination therapy in CRPC.
Compassionate Use Program (CUP) with Ruxolitinib in Mexican Patients with Primary Myelofibrosis (PMF), Post – Polycythemia, Vera Myelofibrosis (PPV – MF), and Post–Essential Thrombocythemia Myelofibrosis (PET – MF)
Authors: Pablo Vargas, Roberto Ovilla, Martha Alvarado, Manuel Lopez, Rafael Hurtado Monroy, Juan_Carlos Solis, Alejandro Limon, Gladys Agreda, Salvador Silva, Juan Julio Kassack, Saida Zavala, Carlos Aguilar, Enrique Baez, Esperanza Barrera, Antonio Osuna, Javier Morales, Aquileo Herrera
Journal: Blood (2012)
The association of PTEN loss on outcome in patients with early high-risk prostate cancer (CaP) treated with adjuvant docetaxel following radical prostatectomy (RP).
Authors: D. Keizman, Z. Zhang, V. J. Sinibaldi, A. DeMarzo, B. Gurel, T. Lotan, J. Hicks, E. Rosenbaum, E. S. Antonarakis, J. J. Kim, M. A. Carducci, M. A. Eisenberger
Journal: Journal of Clinical Oncology (2011)

4576 Background: Loss of the PTEN tumor suppressor and subsequent activation of the PI3K pathway is common and has potential clinical and therapeutic value in CaP. We examined the PTEN status of primary tumors in pts who underwent adjuvant docetaxel tx in a prospective clinical trial. Methods: Of the 77 pts enrolled in a prospective multi-institutional adjuvant docetaxel trial (TAX 2501, J Urol 2007), we prospectively collected 56 primary tumor pathology specimens suitable for analysis of PTEN status by immunoreactivity (IHC) and/or fluorescence in situ hybridisation (FISH) assay. Protocol defined progression included a PSA of ≥ 0.4 ng/ml, radiological/pathological evidence of recurrent disease or death from any cause. Univariate and multivariable analyses based on the Cox proportional hazards regression model were used to analyze the independent association of PTEN and other known prognostic factors with progression free survival (PFS). Results: PTEN loss was observed in 37/56 pts (66%). Pts with PTEN loss vs detectable PTEN were balanced regarding clinical stage, combined Gleason score, seminal vesicles and surgical margins involvement, and lymph nodes status. Pts with a detectable PTEN had a significantly higher pre-RP PSA (median 14 vs 8.6 ng/ml, p=0.015). 41/56 (73.2%, median followup of 37.5 months, range 10.4 to 44.5) progressed with an overall median PFS of 13 months (mos) (95% CI 9.8-15.8). Independent prognostic factors of progression by multivariate analysis were: seminal vesicles involvement (HR 2.19, p=0.024), combined Gleason score 9-10 (HR 2.46, p=0.027) and PTEN loss (HR 2.36, p=0.037). PFS on pts without PTEN loss (median not reached at a followup time of 37.5 mos, range 10.4 – 44.5 mos) was significantly longer (log rank test, p = 0.026) compared to those with undetectable PTEN (median PFS 12.9 mos, 95% CI 9.7-15.3). Conclusions: PTEN loss may be an independent prognostic factor associated with poorer outcome of pts with early high risk CaP treated with adjuvant docetaxel following RP. These findings may have important prognostic and therapeutic implications in CaP.