tbuckley/cabot-search huggingface dataset:
Meta-analysis of randomized trials comparing cisplatin versus carboplatin-based regimens for the first-line therapy of metastatic transitional cell carcinoma of the urothelium (TCCU).
Authors: G. Sonpavde, M. D. Galsky, G. J. Chen, J. Bellmunt, B. J. Roth, R. Petrioli, T. E. Hutson, L. Dogliotti, R. Dreicer, W. K. Oh
Journal: Journal of Clinical Oncology (2011)

247 Background: Cisplatin-based chemotherapy is the first-line treatment standard for metastatic TCCU, although carboplatin is substituted for cisplatin-ineligibility, tolerability, and ease of administration. Since definitive data comparing cisplatin- versus carboplatin-based chemotherapy are lacking, a meta-analysis of published randomized trials was performed. Methods: PubMed was searched for articles published in the English language from 1966 until 2010 and abstracts presented at the American Society of Clinical Oncology Annual Meeting between 2000 and 2010 were searched to identify relevant trials. Eligible studies included prospective randomized trials evaluating cisplatin- versus carboplatin-based regimens in cisplatin-eligible patients with metastatic TCCU. Individual patient data were not available and progression and survival data were inconsistently reported. Therefore, the analysis focused on overall (OR) and complete response (CR). The Mantel-Haenszel method was used for combining trials and calculating pooled risk ratios (RR). Results: A total of 286 patients with metastatic TCCU from 4 randomized trials (3 phase II and 1 phase III trial) were included. Chemotherapy regimens included MVEC (methotrexate, vinblastine, epirubicin, cisplatin) vs. MVECa (methotrexate, vinblastine, epirubicin, carboplatin), MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) vs. MCAVI (methotrexate, carboplatin, vinblastine), MVAC vs. paclitaxel plus carboplatin, and gemcitabine plus cisplatin vs. gemcitabine plus carboplatin. Cisplatin-based chemotherapy was associated with a significant improvement in the likelihood of CR (RR=3.973 [95%CI: 1.562 – 10.110], p =0.004) and OR (RR=1.336 [95%CI: 1.043 – 1.712], p=0.025). Conclusions: Cisplatin-based as compared with carboplatin-based combination chemotherapy significantly increases the likelihoods of both OR and CR, in patients with metastatic TCCU. In the absence of definitive phase 3 trials, these results support cisplatin-based regimens as the preferred first-line treatment for cisplatin-eligible patients with metastatic TCCU. No significant financial relationships to disclose.
Renal cancer treatment in Spain: An online survey.
Authors: I. Duran, P. Sanchez Maurino, J. Garcia-Donas, D. R. Berthold
Journal: Journal of Clinical Oncology (2011)

397 Background: Renal cancer incidence has increased in the last decades. Many treatment options have also been developed in this period. Knowledge about oncologists' attitudes in the management of this disease could help to implement better treatment protocols. Methods: An online survey about therapeutic options for renal cancer was developed by an expert committee. Oncologists with expertise on the treatment of genitourinary malignancies that fulfilled all inclusion criteria in Spain were listed (n=200) and 80 were randomly selected to complete the survey. Survey items considered renal carcinoma management in the daily clinical practice. The questionnaire posed multiple tests, protocols, or therapeutic options. Results: From the 80 selected oncologists, 53 responded to the online survey (66% response rate). The mean number of newly diagnosed cases per year was 201 (SD: 12) patients of whom 15 corresponded to renal carcinoma. Seventy nine per cent of participants reported to apply a protocol for treatment decisions, being the NCCN recommendations the most frequently followed (54.7%). Surprisingly, local or European recommendations were scarcely used. When asked about management of metastatic disease, most physicians (83%) reported that they would use sunitinib as the preferred first line treatment for good or intermediate prognosis patients. If further treatment would be required, 69.8% (n=37) and 79.2% (n=42) of oncologists would recommend a change in the mechanism of action by switching to an mTOR inhibitor (everolimus) for first and further relapses, respectively. Regarding the management of first line non-clear cell histologies, almost half of the physicians would utilize a TKI, while 38% would prefer an mTOR inhibitor. Conclusions: NCCN are the most frequently followed recommendations. There is agreement among oncologists about which treatment should be used for renal carcinoma after first line treatment failure by switching the mechanism of action of the selected treatment. The management of non-clear cell patients remains a matter of debate with no consensus among the participants. No significant financial relationships to disclose.
Preliminary safety results of an Italian early-access program (EAP) with cabazitaxel plus prednisone (CbzP) in patients with docetaxel-refractory metastatic castration-resistant prostate cancer (mCRPC).
Authors: Sergio Bracarda, Giuseppe Di Lorenzo, Donatello Gasparro, Paolo Marchetti, Francesco Boccardo, Andrea Martoni, Giacomo Carteni, Giuseppe Fornarini, Valentina Baldazzi, Luigi Dogliotti, Caterina Messina, Michele Sisani
Journal: Journal of Clinical Oncology (2012)

253 Background: A significant number of docetaxel (D) refractory mCRPC patients (pts) have a life expectancy of &gt; 15 months and ask for additional efficacious treatments. In the phase 3 TROPIC trial treatment of mCRPC patients with CbzP who progressed during or after docetaxel resulted in a statistically significant overall survival benefit compared with mitoxantrone / prednisone (Lancet 2010). This survival benefit supported establishment of a global early access program (EAP), allowing pts with mCRPC to have access to the drug prior to its commercial availability. Here we describe preliminary safety results from the EAP in Italy. Methods: We report here the data of the first 16 mCRPC patients (out of the 123 enrolled by 19 Italian centers until Sept 2011 in EAP) treated with Cbz (25mg/m 2 Q3W) plus P(10mg bid). Results: Pts were median age 73.5 years (&gt;75 years 38%), ECOG PS-0 81.3% and had received a median of 7 prior cycles of D (median cumulative D dose 562.5mg). Median time from last D dose to inclusion was 7.1 months. Overall, 62.5% (10 Pts) had 2 or more metastatic sites (bone 94%, regional/distant lymph nodes 25% and 44%, lung 12.5%, other sites 19%). A limited number of relevant adverse events (AE) were observed. All grade AEs were seen in 14/16 pts (81.3%), with 4/16 pts experiencing grade 3/4 leukopenia, 8/16 pts grade 3 - 4 neutropenia, one patient with febrile neutropenia and one with hypertransaminasaemia. Grade 1-2 asthenia and fatigue were experienced respectively by 2 pts. No grade 3 / 4 diarrhea, vomiting or constipation were observed and no AEs results in death. All pts received at least 2 cycles of CbzP (2÷5) and only one patient permanently discontinued treatment (disease progression). Conclusions: This preliminary analysis of Italian pts enrolled in the EAP provides real world safety data and suggests a good safety profile of cabazitaxel even in heavily pretreated pts, which is in agreement with Italian experience in TROPIC. Results of the entire Italian cohort with a longer follow-up will be presented.
Intermittent androgen-deprivation therapy in the management of castrate-resistant prostate cancer (CRPCa): Results of a multi-institutional randomized prospective clinical trial.
Authors: M. Organ, L. Wood, D. Wilke, C. Skedgel, K. Thompson, S. North, T. Cheng, S. Winch, R. Rendon
Journal: Journal of Clinical Oncology (2011)

131 Background: Patients who develop CRPCa typically continue on androgen deprivation therapy (ADT). Whether these patients need to remain on ADT has not been well studied. We conducted a multicenter randomized trial to compare intermittent versus continuous approach to ADT in CRPCa patients. Overall survival, health related quality of life (QOL) and cost were the main endpoints. We hypothesized that the intermittent approach would be cost-saving while maintaining similar oncologic and QOL outcomes. Methods: CRPCa patients were randomized 1:2 to continuous or intermittent luteinizing hormone releasing hormone agonists (LHRHa). Patients were followed with clinical assessments, laboratory investigations, and QOL questionnaires (EORTC QLQ-C30 or PROSQOLI) every 2 months. If the serum testosterone rose above castrate levels (1.75nmol/L), LHRHa were re-initiated. The study was designed to close if &gt;50% of patients needed to restart ADT in the intermittent arm. Results: 31 patients were followed with a median follow-up of 26.8 months; 18 in the intermittent arm and 13 in the continuous. 12/18 patients on the intermittent arm were re-initiated on LHRHa at a median time of 17.9 months. There was no difference in overall or cancer-specific survival between the two arms. There was no statistically significant difference in QOL between the two arms at 0 and 12 months. The total mean costs at 24 months were significantly lower in the intermittent arm (3135 $CAD vs 8253 $CAD, p=0.0167) compared to the continuous arm largely due to the reduced costs of the LHRHa. Conclusions: We have observed that intermittent ADT in patients with CRPCa, using a testosterone of &gt;1.75 ngmol/L as a trigger to re-initiate LHRHa, results in a substantial cost savings with no negative impact on oncologic and QOL outcomes. These findings need to be corroborated in a study with a larger sample size. [Table: see text]
Comparing the treatment outcomes between unresectable and recurrent cases receiving gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer: Pooled analysis of two prospective studies.
Authors: Takashi Sasaki, Hiroyuki Isayama, Yukiko Ito, Ichiro Yasuda, Nobuo Toda, Hiroshi Yagioka, Saburo Matsubara, Keiji Hanada, Hiroyuki Maguchi, Hideki Kamada, Osamu Hasebe, Tsuyoshi Mukai, Sumihiro Okabe, Iruru Maetani
Journal: Journal of Clinical Oncology (2012)

331 Background: We previously conducted two prospective studies (phase II study and randomized phase II study) of gemcitabine (GEM) and S-1 combination chemotherapy. The purpose of this study was to clarify the difference of treatment outcomes between unresectable and recurrent cases receiving GEM/S-1 combination chemotherapy in patients with advanced biliary tract cancer. Methods: The data of two prospective studies were combined for the analysis. In these studies, GEM was administered intravenously at a dose of 1,000 mg/m 2 over 30 min on days 1 and 15, repeated every four weeks. S-1 was administered orally at a dose of 40 mg/m 2 b.i.d. on days 1-14. Tumor response was assessed every two cycles using RECIST version 1.0. The treatment was continued until disease progression, unacceptable toxicity or patient refusal occurred. Results: Fifty-five unresectable cases and ten recurrent cases were enrolled in this analysis. Patient characteristics were similar between each group except the baseline sum of longest diameter, which was used as a measurement of tumor volume (unresectable 9.0 cm vs recurrent 2.8 cm). Response rates of unresectable and recurrent cases were 25.5% and 40.0%, respectively. Dose intensities of each group were statistically different (gemcitabine 96.8% vs 83.5%, p=0.03; S-1 91.8% vs 75.9%, p=0.03). The median time-to-progressions of unresectable and recurrent cases were 5.7 months and 8.7 months, respectively (p=0.14). The overall survivals of each group were 9.6 months and 16.1 months (p=0.10). Conclusions: In recurrent cases, tumor volume was smaller and dose intensity was lower than that of unresectable cases. Recurrent cases showed better treatment outcome comparing to unresectable cases. Therefore, unresectable and recurrent cases should be analyzed separately in the future study.
Crystal structure of Pla l 1 reveals both structural similarity and allergenic divergence within the Ole e 1–like protein family
Authors: Teresa Stemeseder, Regina Freier, Sabrina Wildner, Julian E. Fuchs, Peter Briza, Roland Lang, Eva Batanero, Jonas Lidholm, Klaus R. Liedl, Paloma Campo, Thomas Hawranek, Mayte Villalba, Hans Brandstetter, Fatima Ferreira, Gabriele Gadermaier
Journal: Journal of Allergy and Clinical Immunology (2016)
Cost comparison of laparoscopic partial nephrectomy and robot-assisted laparoscopic partial nephrectomy.
Authors: R. L. O'Malley, T. Kowalik, M. H. Hayn, T. B. Collins, H. L. Kim, T. Schwaab
Journal: Journal of Clinical Oncology (2011)

402 Background: Although nephron-sparing surgery is the standard of care for the treatment of small renal masses, partial nephrectomy (PN) remains under-utilized. A potential reason for the discrepancy is the desire for minimally invasive surgical approaches but limitation of the advanced laparoscopic techniques needed to perform PN. Robot-assisted surgery has eased the transition to minimally invasive prostate surgery and may also do so for PN, although some believe costs may be prohibitive. The purpose of this investigation was to quantify the cost of robot-assisted PN (RAPN) compared to laparoscopic PN (LPN). Methods: An institutional renal tumor database was used to identify consecutive patients with normal renal function who underwent RAPN for a localized renal mass by a single surgeon who had performed &lt; 25 previously. The 35 RAPN patients were compared to the last 35 similar patients who underwent LPN by a surgeon who had performed &gt; 150 previous LPNs. Surgical outcomes were compared. Because room time, length of stay and Cxs were similar, cost was compared based only on the total operating room charges (ORC). Total ORC included surgeon and anesthesia fees, as well as labor and supply costs. The depreciation of the robot was included in the ORC as a higher per unit time charge than for LPN. Data on charges were available for the first 29 RAPN patients which were then compared to the last 29 LPN patients. Results: Dates of operation ranged from October 2008 to July 2009 for LPN and January 2010 to August 2010 for RAPN. Patient and tumor characteristics were similar between groups, except tumor size, which was larger in the RAPN group (3.6 ± 1.8 cm vs. 2.7 ± 0.9 cm, p = 0.007). Cxs, surgical and oncologic outcomes were similar. Mean ORC (IQR) for the LPN group was $28,606 (4,796) and for the RAPN group was $30,874 (20,389) representing a difference of $2,269. If you subtract an additional $858 for the average yearly inflation rate (3%), the difference is $1,411. Conclusions: RAPN is a safe option with perioperative outcomes similar to those of LPN performed by an experienced surgeon. A cost difference of $2,269 per procedure as estimated using ORC may decrease as the experience of the operating room staff and surgeon increase. No significant financial relationships to disclose.
Experience of the use of trabectedin in pretreated unresectable, advanced, or metastatic soft tissue sarcoma in nine centers in Lebanon on a compassionate-use basis.
Authors: G. Y. Chahine, M. Ghosn, J. G. Kattan, J. A. Makarem, R. Farah, F. G. Kamar, E. A. Tueni, M. Saade, W. Saad, M. Massoud
Journal: Journal of Clinical Oncology (2011)

e20533 Background: Soft tissue sarcoma (STS) comprises a large variety of rare malignant tumors. Development of distant metastasis is frequent, even in patients undergoing initial curative surgery. Trabectedin, a tetrahydroisoquinoline alkaloid isolated from the Caribbean marine tunicate Ecteinascidia turbinata, was approved in 2007 by EMEA for patients with advanced STS after failure of previous lines chemotherapy. In this study, we retrospectively analyzed 15 patients who had been treated with trabectedin between 2008 and 2010 in 9 centers in Lebanon on a compassionate use basis. Methods: Fifteen patients with advanced refractory sarcoma were treated with trabectedin on a named patient compassionate basis program. All patients had been heavily pre-treated with at least 2 previous lines of chemotherapy. Results: The patients received a median of three cycles of treatment. Five patients achieved stable disease. The estimated 3 month progression-free survival median was 48%. Four patients experienced early disease progression, and one patient died while on treatment. None of the deaths was due to treatment-related toxicity, but to disease progression. Conclusions: Trabectedin is a generally well tolerated and effective treatment for soft tissue sarcomas STS even in a heavily pre-treated patient population. Major toxicities include changes in liver function tests and nausea. Dose reductions usually allow continuation of treatment. Progression-free survival and overall survival were significantly prolonged in responders and seem not to be inferior to other clinically used second-line treatments.
Meta-analysis of impact of circumcision and vitamin D on occurrence of prostate cancer: Could they act by suppressing anaerobes colonizing areas of prostatic proliferative inflammatory atrophy?
Authors: R. Oliver
Journal: Journal of Clinical Oncology (2012)

259 Background: There is evidence that some false positive PSA tests can reflect prostatic inflammation that leads to Proliferative Inflammatory atrophy (PIA) that promotes malignant change. Report from circumcision trials in Africa suggest that dominant bacterial flora in un-circumcised men was anaerobes. As circumcised men have a lower incidence of PC this presentation reviews the literature on lack of circumcision and that on Vitamin D deficiency and as a cause of diminished host surveillance that could have potential to synergise as causes of PC. Methods: Three papers reporting incidence of PC in Jewish and non-Jewish men undergoing prostate biopsy for prostate symptoms and 7 series reporting case controlled studies published between 1952 and 2001 have provided data on circumcision and PC risk. There were 10 papers referred to in the IARC 2008 report on plasma 25-hydroxyvitamin D and PC. These have been reviewed together with 8 more published from 2008-10 and 3 that have examined impact of an index of life-time sun exposure on PC risk. Results: The 2 of 3 series of prostate biopsy reported 1951-65 demonstrated significant excess and 1 a non-significant excess of PC in the non-Jewish population. Of the 7 case controlled reported from 1971-2001, only 1 reported significant (OR 1.38) and 1 non-significant (OR 1.15) excess of lack of circumcision in those with prostate cancer, the remaining 6 studies having an excess cancer in those who have been circumcised (OR 0.50 – 0.82 pooled risk 0.70). Only 1 of the 18 plasma 25-OH Vit D series showed significant reduction of PC overall (6 did have reduction in prognostic subsets though 2 had higher incidence in the same sub-groups. In contrast all 3 series that have examined an index of life-time sun exposure showed significant reduction of PC (OR 0.18, 0.32 and 0.52 n= 850). Conclusions: The inconsistencies in the circumcision data suggest that it is not the surgery alone but the confounding variable of the hygiene rules that at least contribute to the reduced PC in Jewish men, and mirrors the similar differences seen in the protective value against AIDS of circumcision in Xhosa African and Asian Muslim men.
Biochemical outcomes for patients with intermediate-risk, organ-confined prostate cancer treated with I-125 interstitial brachytherapy monotherapy.
Authors: Anna Thi Huyen Tran, Paula Mandall, Ric Swindell, Peter Hoskin, David Bottomley, James Wylie
Journal: Journal of Clinical Oncology (2012)

192 Background: Treatment with low dose rate brachytherapy (LDR-BT) monotherapy is well established for low risk prostate cancer. The routine use of LDR-BT in intermediate risk (IR) is more controversial and is often combined with additional external beam radiotherapy (EBXRT). We report the biochemical outcome of a large cohort of patients with IR disease treated with LDR-BT monotherapy. Methods: A multi-institutional prospective database identified 615 patients with IR prostate cancer treated with I-125 interstitial BT between 2003–2007. IR was defined using Memorial Sloan-Kettering Cancer Centre (MSKCC) definition of either T2b, or Gleason score (GS) 7 or raised initial PSA (iPSA) 10.1-20ng/ml. Patients receiving additional EBXRT were excluded. Biochemical failure was defined by both ASTRO (3 rises past nadir) and Phoenix criteria (nadir plus 2). Kaplan-Meier methods were used to estimate biochemical no evidence of disease rates (bNED) and univariate analyses used to identify potential prognostic factors. Results: The median age was 64 years (range 49–82). Forty-three patients had stage T2b, 180 had iPSA 10.1-20 and 392 had GS 7 disease. Only 108 received androgen deprivation therapy (ADT) prior to implant. Median follow up was 5.0 years. The 5-year bNED rates (95% confidence interval) by ASTRO are 85.5% (82.0–88.3%) and for Phoenix 83.7% (80.0–86.7%). Use of ADT, GS 3+4 versus 4+3, and dosimetric indices were not significant prognostic variables. When stratified by risk factor (T2b, GS7 or raised iPSA) raised iPSA correlated to poorer outcome only by Phoenix criteria (by Phoenix p=0.001, by ASTRO p=0.311). Conclusions: We have demonstrated good biochemical control for IR patients treated with LDR-BT alone. No additional benefit was seen with the use of ADT. We believe LDR-BT alone is an effective treatment option in selected IR prostate cancer patients with comparable outcome to other treatment modalities such as surgery or EBXRT.
Mechanisms of Apoptosis Induction by BH3 Inhibitor ABT-737 in AML.
Authors: Michael Andreeff, Rooha Contractor, Peter P. Ruvolo, Xingming Deng, Ismael Samudio, Yue-Xi Shi, Teresa McQueen, Rui-Yu Wang, Wendy Schober, Xiaoyang Ling, Frank C. Marini, David Harris, Zeev Estrov, James McCubrey, W. Stratford May, Marina Konopleva
Journal: Blood (2005)
Promotes Gene Expression by Disrupting the DNA Binding of the AML1/ETO and HDAC1 Repressor Complex.
Authors: Shujun Liu, M. I. Klisovic, T. Shen, J. Yu, G. Dai, L. Huynh, T. Vukosavljevic, S. Whitman, D. Perrotti, G. Marcucci
Journal: Blood (2004)
Sequential RCHOP, Radioimmunotherapy and Rituximab Maintenance Improves Early Outcomes in Advanced Stage Follicular Lymphoma: 5 Year Outcomes from SWOG 0801
Authors: Paul M. Barr, Hongli Li, Richard Burack, Michael LeBlanc, Sonali M. Smith, Ajay K. Gopal, Justin D. Floyd, Daniel O. Persky, Oliver Press, Richard I. Fisher, Jonathan W. Friedberg
Journal: Blood (2016)
Drugging the Undruggable Ras — Immunotherapy to the Rescue?
Authors: Carl H June
Journal: New England Journal of Medicine (2016)

Metastatic gastrointestinal cancers that express products of mutant KRAS genes have one of the most dismal outcomes of all solid tumors and present an unsolved problem in cancer medicine. An activating point mutation in one of genes encoding Ras was the first somatic point mutation identified in a human cancer, and its discovery established the role of somatic mutations as the common driver of oncogenesis.1,2 The presence of a T-cell immune infiltrate in surgical specimens at the time of diagnosis is more prognostic of survival than anatomic Dukes staging,3 which suggests that natural immune surveillance can have a powerful . . .
Mucin 20 (MUC20) Modulates Proteasome Assembly Chaperones through the c-MET Pathway and Is a Biomarker of Proteasome Inhibitor Sensitivity in Myeloma
Authors: Huihan Wang, Veerabhadran Baladandayuthapani, Heather Yan Lin, Xiaobin Wang, Bingzong Li, Xing-Ding Zhang, Isere Kuiatse, Hua Wang, Dongmin Gu, Liye Zhong, Wencai Ma, Richard E. Davis, Robert Z. Orlowski
Journal: Blood (2014)