tbuckley/cabot-search huggingface dataset:
Phase II trial of combination therapy with intravenous bevacizumab (B), oral satraplatin (S), and prednisone (P) in docetaxel-pretreated (DP) metastatic castrate-resistant prostate cancer (CRPC).
Authors: U. N. Vaishampayan, L. K. Heilbrun, B. Dickow, E. I. Heath, D. W. Smith, K. Baranowski, M. L. Cher, I. Powell, J. E. Pontes, J. A. Fontana
Journal: Journal of Clinical Oncology (2011)

152 Background: Satraplatin is an oral platinum that has demonstrated efficacy and tolerability in metastatic CRPC. Bevacizumab has revealed safety and efficacy in advanced prostate cancer, and synergy was noted between platinum based chemotherapy and B. Methods: Primary endpoint was time to progression (TTP). Latter wasdefined per RECIST 1.0 or onset of a skeletal event, or &gt; 2 new areas of bone metastases. DP metastatic CRPC patients were eligible. S 80mg/m 2 orally on days 1-5, P 5 mg twice daily, and B 10mg/kg on day 1, and 15mg/kg on day 15 were administered in 35 day cycles. Results: 31 patients enrolled (13 African American and 18 Caucasian) to complete accrual. Median age was 67 years (range 50-85 years) and 21 patients (68%) were &gt; 65 years of age. Median pretherapy PSA was 180.7 ng/ml (range 4.7-1,433 ng/ml). 21 (68%) had bone pain, Gleason score was &gt; 8 in 20 (65%) patients. Pretherapy 12 patients had measurable disease progression, 17 (55%) had bone scan progression, and 8 had PSA only progression. 176 cycles have been administered; median 4 cycles (range 0-12 cycles). Grade 4 toxicities noted were, pulmonary embolism in 2 patients and thrombocytopenia in 1 patient. Grade 3 toxicities observed were neutropenia and hypertension in 3, anemia in 7 and , thrombocytopenia and diarrhea in 2 patients each. No treatment related deaths. 29 patients are response evaluable to date; 10 (34%) had a ≥30% PSA decline and 3 (10%) had a &gt; 90% PSA decline. Of 12 patients with MD, 2 had a response and 7 had stable disease. Median TTP was 7.4 months (90% CI 4.8-12.8 months) and median survival was 11.2 months (90% CI 9.1-18.3 months). 47% of patients were alive at 12 months. Genotype characterization for excision repair cross-complementation group 1 (ERCC1) polymorphism was performed in 17 patients with 9 having homozygous (CC), 3 with heterozygous, (CT) and 2 patients with absence of ERCC expression respectively. Conclusions: The combination was tolerable and revealed promising efficacy in metastatic CRPC. ERCC1 testing will be correlated with outcome endpoints. Supported in part by Genentech Inc and GPC Biotech. [Table: see text]
Long-term survival in patients with metastatic renal cell carcinoma (mRCC) in the era of new targeted therapies: Five-year follow-up in a single Spanish medical institution (Genito-Urinary Tumor Unit, University Hospital 12 de Octubre).
Authors: G de Velasco Oria, J Sepulveda, F Villacampa, I Ghanem, Daniel E. Castellano
Journal: Journal of Clinical Oncology (2012)

376 Background: Recently, new targeted therapies have proved the efficacy in patients with mRCC in terms of progression-free survival (PFS) and overall survival (OS). There is also growing evidence that successive targeted treatments has achieved objective responses and sustained time to progression. Here, we report data from our insitution analysing the OS benefit of continuing targeted therapy after disease progression. Methods: We identified 58 metastatic clear cell RCC patients who started targeted therapy between September 2005 and December 2008. The data were collected from our clinical trials registry. The patients were evaluated for differences in baseline characteristics and known prognostic factors (PFs) in metastatic RCC. We assessed overall survival for all patients. Results: We identified 58 pts, 24 are still alive (43%). Median age was 56 (range 31–78). ECOG PS 0/1/2: 33/24/1. 46% (27) had diagnosis to treatment intervals &lt; 1 year. Sites of metastatic disease included: lung 46%(26), bone 32%(19), hepatic 29%(17) and retroperitoneal 24%(14). Nephrectomy was pesented in 90% of all pts. The number of metastases location was: 1/2/3: 32%/11%/7%. The drugs administered are listed in table. Median number of treatments: 3 (range 1–7). The median overall survival (OS) was 44 months and the 3- year OS was 60.4%. Pts by MSKCC risk-group were: favourable prognostic (FP) 19%, intermediate prognostic (IP) 63%, poor prognostic (PP) 18%. The overall survival for FP group was not reached, and 3-year OS was 81%; for IP group the median survival time was 44 months and 3-year OS was 59%; and for PP group the median survival time was 25 months. Conclusions: The survival for patients with mRCC who receive multiple lines of targeted therapy has increased to close to 4 years. These results indicate a clear shift in the evolution of mRCC but lack a great deal about what the best sequence. Final analysis of the best sequence of treatment will be presented at the meeting. [Table: see text]
Neoadjuvant temsirolimus in high-risk renal cell carcinoma: Results from a single-center prospective study.
Authors: A. A. Sheikh, A. Gharajeh, S. J. Hotte, J. H. Pinthus, A. Kapoor
Journal: Journal of Clinical Oncology (2011)

387 Background: The current first-line treatment for advanced renal cell carcinoma (RCC) includes targeted therapy with or without cytoreductive radical nephrectomy. There is a paucity of data as to the effectiveness of adjuvant and neoadjuvant treatment before radical nephrectomy for localized high-risk or advanced disease. We initiated a trial of neoadjuvant Temsirolimus before radical nephrectomy for locally advanced and metastatic RCC examining tumor response and survival. Methods: Patients who presented with advanced RCC were offered enrolment into a prospective, single-centre, ethics approved trial with 12 weeks of temsirolimus before radical nephrectomy. Biopsy tissue was obtained at enrollment and at time of cytoreductive nephrectomy for diagnosis. Patients were administered 25 mg in temsirolimus on a weekly basis for 12 weeks, and then underwent radical nephrectomy. Computed tomography scans and biomarkers were obtained on enrolment, 6 weeks and 12 weeks (before nephrectomy). Ongoing outcome and survival data were analyzed. Results: Eight patients were enrolled into the trial. Patient #1 (10-cm renal mass with bulky adenopathy T2N2M0) had no evidence of disease (NED) at 6 months post-nephrectomy. Patient #2 (9-cm renal mass, bulky adenopathy, pulmonary metastases T2N2M1) also had NED at 6 months postnephrectomy. Patients #3 and #4 experienced regression of the primary mass and have recently undergone uneventful surgery with follow-up pending. Patients #5 and #6 expired prior to the full course of therapy, but had diagnoses other than RCC. Patient #7 experienced disease progression, however, this patient's nephrectomy was delayed by 3 months due to an unrelated myocardial infarct. Patient #8 experienced adverse events. Conclusions: Our findings suggest that neoadjuvant temsirolimus before radical nephrectomy for advanced RCC may improve disease regression post-surgery, and may lead to disease resolution in patients with low-volume disease. Randomized studies with longer term follow-up is necessary to assess overall progression-free survival and overall survival. [Table: see text]
Variation in the flowering gene SELF PRUNING 5G promotes day-neutrality and early yield in tomato
Authors: Sebastian Soyk, Niels A Müller, Soon Ju Park, Inga Schmalenbach, Ke Jiang, Ryosuke Hayama, Lei Zhang, Joyce Van Eck, José M Jiménez-Gómez, Zachary B Lippman
Journal: Nature Genetics (2016)
Neoadjuvant platin and bevacizumab in triple-negative breast cancer.
Authors: P. Kern, F. Otterbach, H. C. Kolberg, D. Pott, A. Kalisch, R. Kimmig
Journal: Journal of Clinical Oncology (2011)

e11591 Background: TNBC is associated with a high risk of relapse and metastasis despite higher primary tumour chemosensitivity than luminal A and B breast cancers. However achieving a pCR this triple negative paradox is reversed and it has been shown that in this group of no residual disease excellent long-term survival can be achieved, the pCR being a surrogate marker for long-term survival. Thus efforts are undertaken to enhance the pCR-Rate introducing Platin-analouges and angiogenesis inhibitors. Phenotypic and molecular similarities between TNBC and BRCA1-associated breast cancer suggest that TNBC may share the same sensitivity to platinum analogues as tumours associated with BRCA1 and VEGF is known to be elevated. Methods: This trial was initiated to asses the efficacy of platinum and taxane-based combination therapy compared to a standard chemotherapy with and without bevacizumab. 14 patients with primary breast cancer (all cT2, majority of them G3, and 5 of them basal-like type) received 6 cycles of carboplatin AUC 6 and docetaxel 75 mg/m2 q3w (T-Carb). This was compared in 15 patients (cT1c and cT2, G3) receiving 4 cycles epirubicin 90mg/m² + cyclophosphamide 600mg/m² +/- bevacizumab (8 out of 15: + bevacizumab). 5 patients received 12 cycles taxol 80mg/m² and 9 patients 4 cycles taxotere 100mg/m², 6 of them + bevacizumab. The primary endpoint was pathological complete response, secondary endpoint feasibility. Results: 9 out of 14 patients (T-Carb) experienced pathological complete response. 5 patients with residual disease 1 was ypT1mic, 3 ypT1b and 2 ypT1c. Within the reference group (epirubicin 90mg/m² + cyclophosphamide 600mg/m² +/- bevacizumab) 8 out of 15 patients reached complete response, 7 residual disease (1 was ypT1b, 3 ypT1c, 1 ypT3, 1 ypT4). Treatment was well tolerated, the only Grade III and IV toxicities in the TCarb group were neutropenia, vomiting, edema, joint pain and alopezia. Within the standard chemotherapy schedules (+/-bevacizumab) more patients suffered from Grade III and IV toxicities. Conclusions: The results show a high pCR-rate of 64 % with docetaxel and carboplatin as primary chemotherapy for TNBC with better feasiblity than in the standard chemotherapy arm (+/- bevacizumab).
Sentinel node biopsy (SNB) by indocyanin green (ICG) fluorescence imaging in patients with operative breast cancer.
Authors: K. Hisamatsu, T. Oikawa, S. Shiotani, S. Kuroki, Y. Hachitanda
Journal: Journal of Clinical Oncology (2011)

e11507 Background: Sentinel node biopsy (SNB) is standard method of breast cancer operation. There are two methods in detecting SNB using dye only and radioactive colloid with dye in Japan. We evaluated usefulness of SNB by indocyanin green (ICG) fluorescence imaging in operative breast cancer patients, retrospectively. Methods: From December 2006 to December 2010, 360 cases underwent breast cancer operation and within 253 (70%) casesin clinical node-negative cases underwent SNB by ICG fluorescence imaging. Dye was mixed 1ml ICG and 4ml Indigocarmine. Dye was injected subdermal in the areola. After one minute massage, subcutaneous lymphatic channel draining from the areola to the axilla was observed by Image processing and measuring system (PDE C9830, Hamamatsu Photonics Co). Skin incision was done at the point which fluorescence imaging disappeared. Results: SN was detected 238 cases, detective rate was 96%.The lymph node metastasis was detected 37 cases (15%). Author has been belonged at another hospital until August 2010 and SNB have been done radioactive colloid (phytate radilabelled by Tc98) with dye in this hospital. Radioactive colloid was injected subdermal around tumor at the morning of operation day and Indigocarmine was injected subdermal in the areola. From January 2001 to July 2010, 762 cases underwent breast cancer operation and within 614 (80%) casesin clinical node-negative cases underwent SNB. SN was detected 586 cases, detective rate was 95%. Conclusions: Two methods in detecting SNB using dye only and radioactive colloid with dye were same detection rate. These results suggest that Sentinel node Biopy (SNB) by Indocyanin green (ICG) fluorescence imaging was useful tool in operative breast cancer patients.
Relationship between taxane-induced neuropathy and clinical outcomes after adjuvant chemotherapy.
Authors: B. P. Schneider, M. Wang, V. Stearns, S. Martino, V. E. Jones, E. A. Perez, T. J. Saphner, A. C. Wolff, G. W. Sledge, W. Wood, N. E. Davidson, J. A. Sparano
Journal: Journal of Clinical Oncology (2011)

270 Background: Neuropathy is a common and potentially enduring and disabling complication of adjuvant taxane therapy. Recent studies have identified candidate host single nucleotide polymorphisms (SNPs) associated with taxane-induced neuropathy (Schneider et al. ASCO 2011, abstr. 1000). We therefore sought to determine whether neuropathy was associated with breast cancer recurrence. Methods: This study included 4,950 eligible women with axillary lymph node positive or high-risk node-negative breast cancer who received up to 4 cycles of AC (doxorubicin 60 mg/m 2 and cyclophosphamide 600 mg/m 2 ) every 3 weeks, followed by either: (1) paclitaxel 175 mg/m 2 every 3 weeks x 4 (P3), (2) paclitaxel 80 mg/m2 weekly x 12 (P1), (3) docetaxel 100 mg/m 2 every 3 weeks x 4 (D3), or (4) docetaxel 35 mg/m 2 weekly x 12 (D1). Chemotherapy doses were based on actual body weight. Cox proportional hazards model were used to determine the relationship between neuropathy and disease free survival (DFS) and overall survival (OS) treating neuropathy status as a time dependent covariate and using a landmark analysis. Results: Of 4,702 patients who received at least 1 taxane dose, grade 2-4 neuropathy developed in 20%, 27%, 16%, and 16% in the P3, P1, D3, and D1 arms, respectively. In a model including age, tumor size, nodal status, treatment arm, neuropathy, and the neuropathy- treatment interaction, there was no relationship between neuropathy and DFS and OS in the entire population, for any of the individual treatment arms, or for any breast cancer subtypes, whether analyzed as a time-dependent covariate or using a landmark analysis. Baseline covariates associated with an increase rate of neuropathy included black race (25% vs. 19% grade 2-4, p=0.02) and obesity (21% vs. 19%, p=0.04), but not age. Conclusions: There was no association between taxane-induced neuropathy and DFS or OS in patients treated with contemporary AC-taxane therapy, including weekly paclitaxel. These findings show that taxane-induced neuropathy is not associated with outcome, thus suggesting that validation of SNPs predictive of neuropathy may be useful in identifying patients at higher risk for neuropathy but not taxane benefit and thereby improve therapeutic individualization.
Relationship between lack of patient compliance with adjuvant therapy guidelines and recurrence in early breast cancer.
Authors: D. L. Citrin, R. Neelam, J. F. Grutsch, S. J. Mortensen
Journal: Journal of Clinical Oncology (2011)

215 Background: Modern treatment (Tx) of early stage breast cancer (BC) often requires a combination of surgery, radiation and adjuvant drugs (chemotherapy, hormones and/or Herceptin). Lack of patient compliance is often an issue, due to the prolonged nature of Tx and lack of perceived benefit when there is no clinically overt disease. Methods: We retrospectively evaluated consecutive patients with recurrent BC who had primary Tx for stage I-III BC elsewhere, and were seen at MRMC over an eighteen month period by DLC or RN following relapse. Patients with stage IV or inflammatory BC at initial diagnosis were excluded. All patients in this study were therefore considered failures of primary Tx. Results: A total of 215 patients (median age 44, range 27-74) were included in this study. Sites of recurrence were loco-regional 73, distant mets 117, both 25. 215 (60%) were found to have had inadequate Tx as per NCCN guidelines. The most common deviations from NCCN guidelines were due to patients’ refusal of chemotherapy or hormone therapy. Detailed information about nodal status was available for 208 patients (see table). The proportion of patients with 0-3 nodes positive who received inadequate primary Tx was statistically significantly greater than the proportion of patients with &gt; 3 nodes involved (Pearson Chi Square p &lt; 0.0001). Conclusions: This retrospective study suggests that patient compliance is a key factor in determining efficacy of primary Tx of early BC. [Table: see text]
Tracking Genetically Engineered Lymphocytes Long-Term Reveals the Dynamics of T-Cell Immunological Memory
Authors: Giacomo Oliveira, Eliana Ruggiero, Maria Teresa Lupo Stanghellini, Nicoletta Cieri, Mattia D'Agostino, Raffaele Fronza, Christina Lulay, Francesca Dionisio, Sara Mastaglio, Raffaella Greco, Jacopo Peccatori, Alessandro Aiuti, Luca Biasco, Attilio Bondanza, Antonio Lambiase, Catia Traversari, Luca Vago, Christof von Kalle, Manfred Schmidt, Claudio Bordignon, Fabio Ciceri, Chiara Bonini
Journal: Blood (2015)
May axillary dissection be avoided after micro metastases in sentinel lymph node analyzed by OSNA method?
Authors: A. Velasco, S. Morales, M. J. Panades, S. Gonzalez, F. Vilardell, C. Canosa, E. Iglesias
Journal: Journal of Clinical Oncology (2011)

18 Background: The study of the sentinel node biopsy is a common method to assess axillary involvement before surgical resection. The OSNA assay based on reverse transcriptase loop mediated amplification (RT-LAMP) and quantification of cytokeratin 19 (CK19) mRNA allows a rapid intra-operative detection of the metastases in the sentinel lymph node in breast cancer patients. Pathologists considered micro metastases when the size of the node involvement was between 0.2 and 2 mm and the OSNA method assess micro metastases when the copy number of CK19 is between 250 and 5000. Methods: From a total of 341 patients in which sentinel node had been analyzed, we studied a series of 32 patients whose sentinel nodes had micro metastases assessed by OSNA and who underwent subsequent axillary dissection. Median breast tumour size was 1.6 cm, 10 patients (31%) had less than 1 cm in size and only 6 patients (19%) had &gt;2 cm. 78% of patients shown positive oestrogen receptor and 14 patients (44%) had low Ki67 (&lt;14%). The CK19 mRNA was quantified in all patients (32) resulting in a median value of 540 (210-4800). Results: The median value of the nodes removed by axillary dissection was 14 (9-19). We found tumor invasion in none of them by histopathological conventional study. Conclusions: Since we have found no axillary involvement when the sentinel node have micro metastases analyzed by the OSNA method it seems that quantitative measure of CK19 by OSNA may be a useful procedure in order to avoid axillary dissection, although it would be necessary to perform larger studies to demonstrate this effect.
Fatigue, quality of life, and cognitive functions in metastatic kidney cancer patients with antiangiogenic treatment.
Authors: S. Noal, M. Lange, B. J. Escudier, E. Sevin, S. Dauchy, B. Clarisse, A. Daireaux, I. Leger, C. Rieux, F. Joly
Journal: Journal of Clinical Oncology (2011)

328 Background: Fatigue is commonly reported by patients under anti-angiogenic therapies, with sometimes cognitive complains. However, few studies have explored these problems. A longitudinal multicentric prospective study is ongoing in France on fatigue, cognitive functions, quality of life (QoL), anxiety and depression among metastatic kidney cancer patients receiving anti-angiogenic therapies. Objectives: The main objective is to assess fatigue. Secondary objectives are to assess cognitive functions, QoL, anxiety, and depression. Methods: Assessments are made at baseline, at 3 and 6 months. Evaluations were made by: autoquestionnaire MFI-20 to assess fatigue, FACT-G and FKSI to assess QoL, Spielberger's and Beck's questionnaires to assess respectively anxiety and depression. Cognitive functions were assessed by a neuropsychologist with the Working Memory Index (WAIS-III), Grober and Buschke test, Rey Complexe Figure test, verbal fluency and Trail Making test, exploring respectively working memory, episodic memory and executive functions. Preliminary results are presented. Results: 35 patients were enrolled, and 20 of them had the second assessment at 3 months. Most of patients received sunitinib (51%), others received bevacizumab and interferon, or sorafenib. At baseline, 45% of patients expressed general fatigue and 50% at 3 months (p=0.04). Other domains of fatigue (physical, mental, reduced activity and motivation) did not change over time. At baseline, few patients had cognitive disorders (working memory 6%; executive functions 0%; episodic memory 11%), with no decline at 3 months. However, there was an impairment of QoL in FKSI score (p=0.01) and of FACT-G physical well-being (p=0.01). No differences were found in social, emotional or functional well-being. There was no difference on depression nor on anxiety over time. Conclusions: Fatigue significantly increased during the first 3 months of anti-angiogenic treatment, with no impact on cognitive functions but a decline of QoL. These preliminary findings need to be confirmed by further follow-up and more patients. Final results will be provided with 120 patients. No significant financial relationships to disclose.
Expression and Prognostic Impact of Candidate Suppressor Sequence-Specific Single-Stranded DNA Binding Protein (SSBP2) in AML Using Reverse Phase Proteins Arrays (RPPA).
Authors: Steven M. Kornblau, YiHua Qiu, Wenjing Chen, Hong Liang, Farhad Ravandi, Kevin R. Coombes, Lalitha Nagarajan
Journal: Blood (2007)
Trametinib after disease reactivation under dabrafenib in Erdheim-Chester disease with both BRAF and KRAS mutations
Authors: Thierry M. Nordmann, Freimut D. Juengling, Mike Recher, Christoph T. Berger, Daniel Kalbermatten, Andreas Wicki, Aino Paasinen-Sohns, Gieri Cathomas, Alexandar Tzankov, Thomas Daikeler
Journal: Blood (2016)
Phase I Study of Cladribine (2-chlorodeoxyadenosie), Cytarabine and G-CSF Based Induction Therapy (CLAG) with ATRA (All-trans retinoic acid) and Midostaurin for Relapsed/Refractory AML,
Authors: Giridharan Ramsingh, Andrew Sprau, Peter Westervelt, Ali McBride, Keith E. Stockerl-Goldstein, Ravi Vij, Geoffrey L. Uy, Amanda Cashen, John F. DiPersio, Camille N. Abboud
Journal: Blood (2011)
Is systematic 10 core prostate needle biopsy enough for treatment determination of localized prostate cancer?
Authors: Ryo Kishimoto, Ryuta Tanimoto, Kensuke Bekku, Yasuyuki Kobayashi, Shin Ebara, Takashi Saika, Yasutomo Nasu, Hiromi Kumon
Journal: Journal of Clinical Oncology (2012)

163 Background: To evaluate whether the systematic 10 cores prostate needle biopsy is enough for determination of NCCN risk classification (NRC), we analyzed migration of Gleason score (GS), cancer location, and NRC between pre and postoperative periods in a cohort of patients who underwent radical prostatectomy. Methods: A total of 197 patients were included in this study. These patients were divided into three groups along the number of biopsy cores: less than 10 (L), 10, and more than 10 (M). We compared between three groups about Gleason score, cancer location and NCCN risk classification change (CC) between prostate biopsy and radical prostatectomy specimen. Statistical analysis were performed with chi-square test, and multiple logistic regression with p&lt;0.05, and Bonferroni correction with p&lt;0.017 considered significant difference. Results: The rate of CC in L, 10, M was 55.1%, 43.0%, 26.5%, respectively. On chi-square test rates of CC were significantly different between three groups (P=0.035), but rates of Gleason score and cancer location were not. On univariate analysis, PSA (Odds rate (OR) 0.872 p&lt;0.001), preoperative NRC (low vs. intermediate, and poor, OR 0.157 and 0.241, p&lt;0.001), prostate volume (normal vs. mild or moderate, OR 1.989 p=0.025), the number of biopsy cores (L vs. M, OR 0.293 p=0.011), GS (6 vs. 8, OR 2.374 p=0.021) were correlated with CC. On multivariate analysis, the most important independent predictive factors for CC were preoperative NRC (low vs. intermediate, p&lt;0.001, OR 0.198, 95% CI 0.09-0.45) and PSA (p=0.007, OR 0.903, 95%CI 0.83-0.98), but the number of biopsy cores was not associated CC significantly. Conclusions: Although multivariate analysis showed no significant difference, the more biopsy cores reduced the risk of CC. Systematic 10 core biopsy might be insufficient for accurate diagnosis and treatment decision of prostate cancer.