tbuckley/cabot-search huggingface dataset:
A phase I study of TRC105 (Anti-CD105 [endoglin] antibody) in metastatic castration resistant prostate cancer (mCRPC).
Authors: Fatima H Karzai, Andrea Borghese Apolo, David Adelberg, Ravi A. Madan, James L. Gulley, Philip M. Arlen, Howard L. Parnes, Ann Pierpoint, David R. Kohler, Jane B. Trepel, Douglas K. Price, Seth M. Steinberg, William Douglas Figg, William L. Dahut
Journal: Journal of Clinical Oncology (2012)

3043 Background: Pre−clinical and clinical evidence demonstrates an important role for angiogenesis in mCRPC biology. CD105 (endoglin) is a transmembrane protein expressed on the surface of proliferating vascular endothelial cells. The expression of CD105 is required for the formation of new blood vessels. TRC105 is a human/murine chimeric IgG1 kappa monoclonal antibody that binds to human CD105 (endoglin). It inhibits angiogenesis and tumor growth through inhibition of endothelial cell proliferation, antibody-dependent cellular cytotoxicity, and induction of apoptosis. The primary objective is to evaluate safety and identify the maximum tolerable dose (MTD) of TRC105. Secondary objectives include the assessment of TRC105 pharmacokinetics, PSA response rate, evaluation of progression free survival (PFS), overall response rate (ORR) and overall survival (OS). Methods: Patients with an ECOG performance status (PS) ≤ 2, progressive mCRPC and either chemotherapy-naïve or post-docetaxel treatment were eligible. Six cohorts of patients, on escalating dose levels, receive TRC105 intravenously at doses of 1, 3, 10, 15, or 20 mg/kg IV every 2 weeks (cohorts 1, 2, 3, 5, and 6) or 10 mg/kg IV weekly (cohort 4) on a 4 week cycle. Response is assessed with imaging studies every 2 months for the first four months and then every 3 months thereafter. Results: Sixteen patients are enrolled in cohorts 1-5. Median age is 65 (range 48-87), median ECOG PS is 1 (range 0−2), median Gleason score is 8 (range 6−10), median on−study PSA is 147.5 (range 0.1-3373), and median number of prior (non-hormonal) therapies is 3 (range 0−6). Median time on study is 16 weeks (range 8-28 weeks). One patient experienced a dose limiting toxicity (grade 4 vasovagal episode) in cohort 5. PSA declines were seen in 6 patients ranging from 20% to 57% from baseline. Ten out of 12 patients with measurable soft tissue disease achieved stable disease for at least two cycles. Conclusions: TRC105 is tolerated up to 15 mg/kg every two weeks with early evidence of clinical activity in mCRPC. An additional cohort (6), with dosage of 20 mg/kg, is currently under investigation. Accrual is ongoing to evaluate ORR, PFS, and OS in the phase II portion of this study.
Is chemoradiation feasible for child nasopharyngeal carcinoma ?
Authors: H. Jouhadi, S. Sahraoui, A. Acharki, N. Tawfiq, A. Benider
Journal: Journal of Clinical Oncology (2005)

8558 Background: Nasopharyngeal cancer is the first head and neck cancer in morocco. Children form is frequent representing 5 to 7% of all cases and is histologically dominated by the undifferentiated carcinoma (WHO 3). There is a high incidence of locoregionally advanced disease: stage IVa and IVb (AJCC/UICC 1997) represents 97% of total recruitment. Classical treatment is neoadjuvant chemotherapy (3 courses of BEP protocol) followed by radiotherapy for nasopharynx tumour and cervical nodes. Therapeutic results are characterised by a high rate of failure. For stage IVb failure is due to distant metastasis wich occur in 30 to 40% of cases needing more systemic therapy. For stage IVa the major cause of failure is local relapse wich occur in 40 to 50% of cases requiring more intensive local treatment strategies. The aim of this prospective study is to analyse for stage IVa the benefit for local control of adjunction of low dose weekly cisplatine concomitantly to radiotherapy. Tolerance of this protocol was also analysed. Methods: Between January 1999 and December 2002, a total of 31 previously untreated, histologically confirmed NPC childs, were treated in our center with a new protocol. The protocol is based on 3 courses of neoadjuvant chemotherapy (B.E.P)followed by a concomitant radiochemotherapy wich associate radiotherapy to a total dose of 65 to 70 gray and low dose of cisplatine (20 mg/m2) delivered on a weekly schedule. Eligibility criteria were: histologically confirmed undifferentiated carcinoma of nasopharynx, stage IVa, age less than 18 years and informed consent of patients, parents with approbation of ethic groupe. There were 19 female and 12 male patients and their ages ranged from 10 to 17 years. Results: The minimal follow up was 2 years. The 2 year disease free survival was 67% and the 2 year loco regional free survival was 77%. All patients completed radiotherapy. According to NCI toxicity criteria, acute mucositis (due to radiation) grade 3 was observed in 3% and grade 2 in 22%. Xerostomia grade 1 was observed in 32%. Conclusions: This protocol is tolerated and feasible. The 2 years DFS is increased with this protocol to 67%. These results will certainly change management of child nasopharyngeal carcinoma No significant financial relationships to disclose.
Progressive clonal cytogenetic changes associated with myeloma relapse after allogeneic transplantation following reduced intensity conditioning
Authors: C. K. Lee, M. Zangari, A. Fassas, M. Cottler-Fox, F. van Rhee, R. Thertulien, G. Talamo, B. Barlogie, G. Tricot
Journal: Journal of Clinical Oncology (2005)

6663 The aim of the study is to identify patterns of relapse after reduced intensity conditioning allotransplant (RIC Allo) for high-risk patients with multiple myeloma. Data on relapse were analyzed on 60 consecutive patients (median age 52, range 38 to 68 years), who received grafts from a sibling (n = 49) or unrelated donor (n = 11). Twenty-six patients with chemosensitive disease and high-risk presentation received RIC Allo as consolidation after a single autologous transplant (AT). The remaining 34 patients had either relapsed after (n = 31) or were refractory (n = 3) to prior AT. Fifty-three patients (88%) showed abnormal chromosomes, including 42 with chromosome 13 abnormalities (CA 13) and 25 with hypodiploid chromosomes. Thirty-six patients achieved a complete remission (CR) or near CR, 11 partial remission (PR) and 6 had progressive disease (PD). Twenty-two patients (cumulative incidence 41%) had relapse in a median time of 165 days (range, 37 to 789 days). Of these, 11 patients showed progressive clonal cytogenetic changes at the time of relapse in a median of 167 days (range, 37 to 350 days). Relapse without cytogenetic changes occurred relatively late (median 221, range 62 to 789 days) with a delay in the cumulative incidence curve. Inability to achieve CR or nCR after RIC Allo was the only factor significantly associated with more cases of relapse with cytogenetic changes: 82% (cytogenetic changes+) vs. 27% (cytogenetic changes-), p < 0.05. Pre-transplant disease characteristics, prior donor lymphocyte infusion or development of chronic graft versus host disease did not influence the incidence of cytogenetic changes in relapse. The current data suggests that there may be diverse mechanisms of relapse of myeloma after RIC Allo, possibly related to clonal cytogenetic changes. No significant financial relationships to disclose.
Colorectal cancer: Comparative effects of a autologous hemoderivative vaccine with a CEA vaccine and/or an autologous [CD4+CD25+] vaccine
Authors: E. M. Lasalvia-Prisco, E. Garcia-Giralt, S. Cucchi, J. Larrañaga
Journal: Journal of Clinical Oncology (2005)

2596 Background: In advanced cancer from different primary tumors, our team (E. Lasalvia-Prisco et al, Cancer Biology & Therapy, 2003*; ASCO 2003; ASCO 2004) has reported anti-tumoral effect of an immunotherapy procedure using as immunogen a hemoderivative prepared from autologous blood (AHD). Further studies have suggested that AHD, as polyvalent immunogen, elicits an immune response against tumor-associated antigens released by tumor cells to the blood (i.e. CEA) and an autoimmune response against regulatory or tolerance cells [CD4+CD25+]. Methods: Patients.- Metastatic colorectal adenocarcinoma patients (n= 66), chemotherapy-resistant, high CEA plasma levels, PS<3 were 2-group randomized. Group 1 (n=33), AHD vaccination as has been described*. Group 2 (n=33), 3 successive vaccination procedures: (2a) first 2 months, same procedure than group 1 but CEA instead of AHD as immunogen; (2b) following 2 months, CEA was substituted by an autologous hemoderivative prepared as AHD but from autologous [CD4+CD25+] cells (Wan Fal Ng preparation method) and (2c) last 2 months, regular AHD as immunogen. Assessment.- After each 2-month vaccination, lymphocyte proliferation assays measured as thymidine-H3 incorporation (LPAs) were performed in all patients. Peripheral blood mononuclear cells (PBMC) were used as responder cells and every used immunogen was tested as challenger. Results: When challenged with CEA, LPAs were positive (challenged > 4 x control) in 16/33 pts of group 1, 0/33 of 2a, 0/33 of 2b and 12/33 of 2c. When challenged with AH [CD4+CD25+], LPAs were positive in 15 /33 pts of group 1, 0/33 of 2a, 2/33 of 2b and 10/33 of 2c. When challenged with AHD, LPAs were positive in 17 /33 pts of group 1, 0/33 of 2a, 3/33 of 2b and 16/33 of 2c. All Specificity Controls with [CD4+CD25-] were negative. Group 1 and 2c positive responses were significant (p<0.001). Conclusions: AHD induced a sensitization, at least, to blood-released CEA tumor marker and the autologous regulatory cell population [CD4+CD25+]. The blockage of the tolerance system of regulatory cells could explain the efficacy of the anti-tumoral immune response elicited by the tumor-associated antigens released to the blood. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PharmaBlood
Thermal ablation for the treatment of bone metastases (BM) in patients (pts) with metastatic renal cell carcinoma (mRCC): Experience from IGR.
Authors: Margarida Matias, Frederic Deschamps, Laurence Albiges, Yohann Loriot, Christophe Massard, Karim Fizazi, Thierry De Baere, Bernard J. Escudier
Journal: Journal of Clinical Oncology (2015)

437 Background: Local treatment of BM in mRCC pts comprises different approaches including thermal ablation techniques as well as radiofrequency ablation (RFA) and cryotherapy. We report our experience for the treatment of BM of mRCC pts using thermal ablation. Methods: The medical records of all pts with mRCC submitted to thermal ablation of BM from Feb 2008 to Oct 2013 were retrospectively analyzed. Intention of treatment was recorded in 3 categories: complete treatment of all BM in pts with oligometastatic disease or prevention of skeletal related events (SRE) risk and/or pain relief in pts with multimetastatic disease. The local control rate and prognostic factors for local failure (LF) were analyzed including patient characteristics, extension of disease, BM characteristics and type of treatment. Results: 22 pts with BM of mRCC were treated by thermal ablation techniques, with 32 procedures (3 pts had &gt;=3 BM treated). Histology of primary tumor was clear cell in 20 and chromophobe carcinoma in 2 pts. At time of BM treatment, Heng prognostic score was good, intermediate and poor in 36, 59 and 5% of pts. Median age was 67 yrs (48-85). A majority of men were treated (16/22=73%). In 34%, pts had BM synchronous with the primary. BM presented cortical bone erosion in 69% and neurological structures in the vicinity in 50%. Intention of treatment was complete control of BM in 43% and prevention of risk of SRE and/or pain relief in 57% of pts. Cryotherapy was performed in 72% and RF in 28% of cases. Concomitant cimentoplasty and arterial embolization was performed in 70% and 30% respectively. Pain relief was achieved in 81% of pts. LF occurred in 19% of pts (n=6) (95% CI: 4-33%). The median follow-up was 13.4 months (95% CI: 11-21). Median OS was not reached. 86% of pts are still alive at 12 months. The unfavorable prognostic factors for LF were BM size &gt;50 mm (p=0.035) and neurological structures in the vicinity (p=0.0083). Conclusions: Thermal ablation techniques are treatment options that should be considered in the curative and palliative treatment of BM in pts with mRCC. When indications are carefully discussed, these techniques have the potential to achieve good local control and acceptable survival.
A population-based, case-control study of MC1R variants, ultraviolet light exposure, and melanoma.
Authors: E. Ng, E. Vega-Saenz de Miera, B. Tan, W. Gai, J. D. Goldberg, I. Osman, M. Berwick, D. Lazovich, D. Polsky
Journal: Journal of Clinical Oncology (2011)

8504 Background: Allelic variants of the melanocortin-1 receptor gene (MC1R) are associated with increased melanoma risk, with red hair variants ("R") conferring greater risk than non-red hair variants (
Malignant pleural mesothelioma (MPM): Retrospective analysis of clinicopathologic and survival data of the Veterans Affairs Cancer Registry (VACCR).
Authors: S. Subbiah, T. Tashi, R. Thota, A. R. Sama, P. T. Silberstein, W. Gonsalves
Journal: Journal of Clinical Oncology (2011)

e18002 Background: Malignant pleural mesothelioma(MPM) is a lethal disease and little is known about the outcomes of this disease in the veteran population. We plan to examine the clinicopathological and treatment factors associated with survival in this population. Methods: Retrospective analysis of 928 patients with pleural mesothelioma in the VACCR between 1995 and 2009 was done. Demographic data, tobacco and asbestos exposure, grade, stage, therapy and survival data were extracted. Variables were analyzed with Kaplan-Meier, and Cox models. Results: Median age was 71 yrs with Caucasians being 87.6%, AfricanAmericans were 8.72% and other races making up 3.66% of 928 patients with MPM. Stage at presentation were, stage I - 17.07%, stage II -10.1%, stage- III 18.7%, stage - IV 30.6% and unknown accounted for 23.4%.Histology was available for 218 (Epitheliod 72.4%, Fibrous 17.43%, Mixed 22.01%) grade for 86 ( 1: 12.7%, 2: 5.8%, 3: 66.2%, 4: 16.2%).Tobacco and asbestos exposure rates were 66.7% and 29.95% respectively. Median overall survival was 7.13 mos ( 6.33-7.83).Stage specific survival were I - 9.6 mos (7.36-10.9), II - 10.26 mos (7.96-13.47), III - 6.7 mos (5.6-9.1), IV - 5.3 mos (4.7-6.63), unknown stage - 6.86 mos (5.63-8.96). Non-Metastatic MPM patients who underwent surgery alone or surgery with adjuvant chemotherapy or radiation therapy had superior outcomes compared with patients who received non – surgical treatment (11.7mos vs 7.5 mos, P= 0.003) .Using a Cox proportional hazard model age <65 yrs (P=0.024), histology ( Epitheliod p<0.0001 ) and metastatic disease( P=0.001) were identified as independent prognostic factors. Conclusions: MPM has a uniformly poor prognosis in all stages. Younger age, histology, stage of disease and receipt of surgical therapy are associated with improved outcomes whereas race, grade, asbestos or tobacco exposure did not impact the survival. These prognostic factors should be taken into account when starting or evaluating treatment modalities.
Results of Phase II trial of AUY922, a novel heat shock protein inhibitor in patients with metastatic gastrointestinal stromal tumor (GIST) and imatinib and sunitinib therapy.
Authors: Nai-Jung Chiang, Kun-Huei Yeh, Chang-Fang Chiu, Jen-Shi Chen, Chueh-Chuan Yen, Kuan-Der Lee, Yu-Lin Lin, Li-Yuan Bai, Ming-Huang Chen, Jen-Shi Lin, Youngsen Yang, Kun-Ming Rau, Hui-Hua Hsiao, Yan-Shen Shan, Li-Tzong Chen
Journal: Journal of Clinical Oncology (2016)

134 Background: Our preclinical studies showed that AUY922 treatment could induce downregulation of KIT protein and apoptosis in both imatinib-sensitive and -resistant GIST cells (Autophagy 2013). This prospective, phase II trial evaluated the efficacy and safety of AUY922 in patients with metastatic GISTs after failure or intolerance to imatinib and sunitinib in an Asian population. Methods: Based on the MTD defined in previous phase I study, infusion 70 mg/m 2 of AUY922 was given once weekly, 4 weeks as a cycle. The primary endpoint was disease control rate (DCR, objective response + stable disease ≥ 16 weeks), assessed by computed tomography (CT) scan according to RECIST v1.1 every 8 weeks. Metabolic response was assessed by positron emission tomography (PET)-CT scans performed at baseline and after 4 weeks of treatment. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of informed consent. Results: Between 2011.10 and 2015.01, 25 evaluable patients were enrolled. DCR at 16 weeks was 20% but none had partial response. According to the EORTC-defined PET response criteria, ten patients (40%) had metabolic partial response ( &gt; 25% decrease of SUV from baseline) at 4 weeks after AUY922 treatment. At a median follow-up time of 7.8 months (range, 2.0-33.4 months), median progression-free survival (PFS) was 2.4 months (95% confidence interval (CI), 1.6-3.2 months) and median overall survival was 9.6 months (95% CI, 0-21.1 months). Metabolic partial responders had a trend of better PFS (3.8 vs. 1.9 months in non-responders, P = 0.09). The common adverse events (AEs) were fatigue (82%), visual disturbances (70%), diarrhea (55%). Grade 3/4 AEs included visual field darkening (3.7%), blurred vision (7.4%) and diarrhea (7.4%). Treatment interruption and dose modification were frequently required (62%) in patients with more than 8 weeks of treatment because of grade 2-3 visual field darkening. Conclusions: AUY922 showed modest antitumor activity in heavily pretreated GIST patients. Clinical relevant ocular toxicity was unexpectedly high in current study cohort; its correlation with PK will be further explored. Clinical trial information: NCT 01389583.
Feasibility testing of ecomapping in neuro-oncology caregivers to identify social support networks.
Authors: Echo L. Warner, Kathrine Parnell, Adam Louis Cohen, Howard Colman, Maija Reblin
Journal: Journal of Clinical Oncology (2014)

66 Background: The role of family caregivers (FCGs) is expanding in the U.S. health care system, but caregiver burden may adversely affect health. A functional social network of friends, family, and other acquaintances may alleviate FCG burden and improve FCG health by providing support resources. Ecomaps are visualizations that are created to organize and depict information on the size, quality and function of a person’s social network; and, thus, may be a useful tool for highlighting existing support and identifying where additional support is needed. Our objective was to test the feasibility of ecomapping to identify support networks within a sample of neuro-oncology caregivers. Methods: Participants included 4 spouse caregivers of neuro-oncology patients undergoing treatment at a national cancer hospital. Semi-structured interviews were conducted in person (n=3) and by phone (n=1). Participants either completed or were sent example ecomaps and, using the “think-aloud” approach, were asked to describe their social network. Participants were also asked about the process and usefulness of the ecomap. Interviews were recorded and transcribed and then content analyzed by two members of the research team. Results: All participants were female, mean age 35.5 (SD=5.5) years, caring for husbands whose mean age was 38.2 (SD=7.4) years. The mean length of relationship was 13 years (SD=2.2). All participants found ecomapping to be feasible, acceptable, and useful for identifying sources and types of social support. Network structure and sources of support varied by participant but consistently included religious networks and family. Quality and types of support also varied; each participant identified strengths and weaknesses within their networks. Participants were in favor of using ecomaps to explore their support networks with providers in a clinical setting and desired clinical guidance on developing and interpreting their ecomap. Conclusions: Despite a small sample, this pilot shows evidence for the feasibility and utility of ecomapping. This cost-effective tool could be more widely implemented to identify and harness existing social support and improve neuro-oncology caregiver quality of life.
Clinical response rate at primary tumor site (PTS) following a novel induction chemotherapy (IC) regimen of weekly nanoparticle albumin-bound (<i>nab</i>-)paclitaxel and cetuximab with every-3-week cisplatin and 5-FU (ACCF) versus docetaxel, cisplatin, 5-FU, and cetuximab (TPF + C) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).
Authors: D. Adkins, J. Ley, B. Nussenbaum, J. Diaz, R. Paniello, W. L. Thorstad, H. A. Gay, J. Subramanian, T. M. Wildes, J. Mathai, T. Rachocki, D. I. Kuperman
Journal: Journal of Clinical Oncology (2011)

5560 Background: Achievement of a complete (CR) or partial (PR) response at the PTS to IC with cisplatin and 5-FU correlates with disease control after subsequent definitive radiation-based therapy (RT) in patients with HNSCC. The likelihood of CR/PR after IC is high in T1/2 and low in T3/4 tumors. SPARC, an albumin binding protein that is commonly overexpressed in HNSCC, may facilitate preferential accumulation of nab-paclitaxel at PTS compared to other formulations of taxanes. Methods: The primary objective of the prospective phase II trial was to determine the clinical CR and PR rate at the PTS to an IC regimen of weekly nab-paclitaxel (100 mg/m2) and cetuximab (250 mg/m2) with every 3 week cisplatin (75 mg/m2) and 5-FU (750 mg/m2 per day x3 CIVI) (ACCF) given for two cycles in patients with HNSCC. PTS response assessment was performed by clinical exam using categorical outcomes [CR: 100%↓, near CR: 95%↓, PR: 50-94%↓, or progression]. All patients were treated with a third cycle of ACCF, then definitive chemo-RT. These outcomes were compared to retrospective data from a cohort of 58 patients treated with TPF+C. Results: Thirty patients were enrolled on the prospective trial and all were evaluable for the primary objective. Most (73%) had bulky T3/4primary tumors. PTS response to ACCF is shown in the table: CR/near CR: 16 patients (53%) and PR: 14 patients (47%). In the retrospective analysis, most (83%) had bulky primary tumors. The PTS response to TPF+C was CR: 15 patients (27%), PR: 31 patients (56%), and progression: 9 patients (16%). Conclusions: ACCF is a novel IC regimen that resulted in a high likelihood of a favorable (CR/PR) PTS response in patients with high T stage HNSCC. These outcomes compare favorably to our historical experience with TPF+C. Outcome Prospective ACCF (n=30) Retrospective TPF+C * (n=58) Primary site OP L HP OC 22 7 0 1 37 13 6 2 T stage 1 2 3 4 0 8 11 11 1 9 20 28 PTS response CR Near CR PR Progression Not evaluable 13 3 14 0 0 15 0 31 9 3 * PTS assessment by exam and/or imaging.