tbuckley/cabot-search huggingface dataset:
Explored prognostic factors for survival in patients with advanced GIST treated with standard dose imatinib (IM): Results from the BFR14 phase III trial of the French Sarcoma Group.
Authors: David Pérol, Isabelle Ray-Coquard, Binh Bui Nguyen, Antoine Adenis, Maria Rios, François Bertucci, Florence Duffaud, Didier Cupissol, Christine Chevreau, Emmanuelle Bompas, Julien Domont, Sylvie Chabaud, Jean-Yves Blay, Axel Le Cesne
Journal: Journal of Clinical Oncology (2012)

10092 Background: Factors predicting progression free survival (PFS) and overall survival (OS) of patients (pts) with advanced GIST treated with 400 mg daily dose IM included in the BFR14 study with a median follow up of 54 months (CI95%:47-61) was investigated evaluating added prognostic factors. Methods: 434 pts were included in this prospective multicenter trial from June 2002 to July 2009. After 1, 3 and 5 yrs of IM 400mg/day, pts free from progression were randomly offered to continue or interrupt (I arm) IM. Prognostic factors for overall survival were investigated in the entire cohort (randomized and not randomized pts) included in the BFR14. Survival was defined from the date of inclusion to the date of death for OS or to the first occurrence of disease progression under imatinib or death for PFS. A multivariate cox model including statistical significant baseline characteristics tested in univariate were included in a backward procedure d to identify independent prognostic factors for PFS then OS. Results: As of January 2012, there were 285 progressions (65%) and 161 deaths (37%). The median PFS of the entire cohort was 29 months (CI95%: 24-33) and the 4 and 5-yrs PFS were 31% and 24% respectively. A low tumour volume at inclusion, PS (0), sex (female), CD34 positivity on tumor cells were the four independent prognostic factors of a higher PFS. The 5-yrs OS was 54% (CI95%: 48-60). A higher OS was independently predicted by gender (female), PS (0), platelets count (&lt;400 giga/L) and CD34 expression on GIST cells. Median PFS and OS were slightly superior in this more recent series as compared to B2222 consistently with the improved outcome of patients with low tumor volume. Conclusions: OS and PFS are predicted by gender, PS and CD34 expression in this large series of pts treated with standard dose IM. The biological significance of CD34 expression on tumor cells has to be explored in GIST.
Evaluation of Minimal Residual Disease As a Surrogate Endpoint for Event Free Survival in Childhood B-Lineage Acute Lymphoblastic Leukemia
Authors: Maria Grazia Valsecchi, Meenakshi Devidas, Ausiliatrice Lucenti, Martin Schrappe, Giovanni Cazzaniga, Anja Moricke, Claus R. Bartram, Georg Mann, William L. Carroll, Eric Larsen, Naomi Winick, Giuseppe Basso, Valentino Conter, Martin Zimmermann, Stefan Sushu, Andrea Biondi, Stephen Hunger, Stefania Galimberti
Journal: Blood (2016)
Final results from phase II study of volociximab, an α5β1 anti-integrin antibody, in refractory or relapsed metastatic clear cell renal cell carcinoma (mCCRCC)
Authors: S. Yazji, R. Bukowski, V. Kondagunta, R. Figlin
Journal: Journal of Clinical Oncology (2007)

5094 Background: A critical survival step for proliferating endothelial cells is the ligation of fibronectin in the extracellular matrix to integrin a5β1. Voloxicimab, a chimeric monoclonal antibody, blocks fibronectin binding to a5β1, and induces apoptosis of proliferating endothelial cells. Voloxicimab activity is independent of growth factor stimulus, suggesting that a5β1 signalling occurs downstream of growth factor signalling, and is possibly a final common pathway for the development of neovasculature. Methods: This is a multicenter, open label, phase II study in mCCRCC. Patients (pts) received volociximab 10 mg/kg IV every 2 weeks until disease progression. Pts were evaluated for efficacy every 8 weeks using RECIST criteria. Results: A total of 40 pts were enrolled. All pts were evaluable for safety and efficacy. Median time since first diagnosis was 2.5 years. ECOG score was 0–1 in all pts. Prior nephrectomy occurred in 38 (95%) pts. Nineteen (47.5%) pts had ≥ 2 prior therapy. Twenty one (52.5 %) pts had prior anti agiogenic therapy. Other prior treatment included IL-2 in 15 (37.5%), interferon alpha in 7 (17.5 %), IL-2 + interferon in 2 (5%) pts. Most frequent side effects were fatigue in 27 (67.5%) pts, nausea 14 (35%) pts, dyspnoea 8 (20%) pts and arthralgia 7 (17.5%) pts, of which none were grade 3 or 4. Seven (17.5%) pts had SAEs. Stable disease (SD) was observed in 32 (80 %) pts including 1 confirmed PR. Duration of SD ranged from 2–22 months (mo). Fourteen (35%) pts had time to progression (TTP) between 5.8 to 22 mo: Four (10%) pts had TTP ≥ 14 mo (range 14- 22 mo), 8 (20%) pts had TTP ≥ 6 mo (range 6- 12 mo) and 2 (5%) pts had TTP = 5.8 mo. Median TTP was 4 mo. Median overall survival (OS) has not been reached after 22 mo. OS at 6 mo was 79% and 68% at 22 mo. Six (15%) pts died in the study, 5 (12.5%) pts due to progressive disease and 1 with arrhythmia (unrelated to volociximab). Conclusions: Volociximab is well tolerated at 10 mg/kg q2w. Stable disease is noted in 80 % of pts. Based on clinical activity, a randomized controlled trial is being planned. No significant financial relationships to disclose.
Long-term outcome of sunitinib in metastatic renal cell carcinoma: Single center experience.
Authors: Marco Maruzzo, Umberto Basso, Fable Zustovich, Pasquale Fiduccia, Antonella Brunello, Anna Roma, Patrizia Farina, Elisabetta Bezzon, Alberto Banzato, Filiberto Zattoni, Vittorina Zagonel
Journal: Journal of Clinical Oncology (2013)

e15606 Background: The multi-target tyrosine-kinase inhibitor sunitinib has been widely used in first or subsequent lines of treatment for metastatic renal cell carcinoma (mRCC). Since results of registrative clinical trials may be overestimated due to patient selection, outcome data of sunitinib in the routine clinical practice are warranted. Methods: We retrospectively reviewed clinical data of all consecutive mRCC patients starting sunitinib from March 2006 to September 2012 at our Institution. Results: Eligible were 106 pts, median age 63 years (range 27-89), 70% males, 89% clear cell histology, 87% prior nephrectomy. Sunitinib was prescribed either as first (70%) or second or further line of treatment after cytokines or targeted therapies. Patients received a median of 8 sunitinib cycles (1-49). Median PFS and OS in the first line were 15.0 mo (95% CI= 9.8-20) and 35 mo. PFS and OS in the second or further line were 15 mo (11.7-18.2) and 25 mo. Motzer risk score retained its prognostic relevance both in the first and in the second of further line. Patients who received at least 4 cycles at standard dose (50 mg/d 4 wks on/2wks off) had a significantly better PFS and OS compared to patients who did not (PFS 23.0 vs 12.0 mo p=0.012, OS 49.0 vs 16.0 mo p=0.006). First line pts progressing within three months from starting sunitinib were 18.9% (primary refractory), while 25.7% pts were treated for more than 24 mo (long term responders). Grade 3 or 4 toxicities have been recorded in 35% of pts but only 7 pts (6.6%) discontinued the treatment due to unacceptable toxicities. Conclusions: Sunitinib is active and feasible in a broader population of mRCC pts, with apparently superior PFS and OS results compared to pivotal trials. Better management of drug toxicities, less strict criteria for radiological progression, and availability of further sequential treatments may explain such results. Pts receiving at least 4 full dose cycles achieved statistically significant better outcomes.
Clinical Utility of 68Ga–Prostate-Specific Membrane Antigen PET/CT Scan on Postoperative Assessment of Juvenile Nasal Angiofibroma
Authors: Alok Thakar, Pirabu Sakthivel, Arun Prashanth, Rakesh Kumar, Suresh Chandra Sharma, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2019)

Abstract Prostate-specific membrane antigen (PSMA) is expressed on the endothelial cells of tumor-associated neovasculature of various nonprostatic benign and malignant neoplasms. Positive uptake on PET/CT imaging with 68 Ga-labeled PSMA is noted in a patient with juvenile nasal angiofibroma, and the same is noted to be absent following complete surgical excision. 68 Ga-PSMA PET/CT may be a useful tool for juvenile nasal angiofibroma recurrence identification and in differentiating recurrence from surgical site reparative tissue.
Characterization of the pathogenic mechanism of a novel BRCA2 variant in a Chinese family
Authors: A. Kwong, L. P. Wong, K. Chan, E. Ma, U. S. Khoo, J. M. Ford
Journal: Journal of Clinical Oncology (2007)

10541 Background: Despite the identification of a large number of sequences in BRCA1/2 mutation analyses, many genetic alterations are classified as variants of unknown significance (VUS). Increasing data demonstrates ethnic variation of BRCA mutation. We report a novel BRCA2 VUS in a Chinese family with multiple breast cancers and characterized it as pathogenic by RNA analysis. Method: Peripheral blood was collected from the breast cancer proband and her family who were suspected to have a pathogenic mutation due the segregation of the disease phenotype and the young age of presentation of breast cancer. DNA and RNA was extracted from the blood. The entire coding regions and flanking introns of BRCA1/2 were screened for germline mutations using full gene sequencing and Multiplex Ligation -dependent Probe Amplification. Variant DNA alteration leading to an aberrant BRCA transcript was demonstrated by RT-PCR of the RNA and Polyacrylamide Gel Electrophoresis. Abnormal bands were cloned and direct sequencing conducted. Results: A germline mutation c.7806–9T&gt;G was identified in the proband at the BRCA2 intron 16. This mutation was also found in 3 of her 4 sibling sisters with early breast cancer. The proband's mother harbored the same BRCA2 mutation in DNA extracted from archival gastric tumor tissues. Computational analyses showed that this mutation might give rise to a cryptic splice site for alternative RNA splicing. To confirm the pathogenicity, RT- PCR using specific primers flanking the cryptic splice site and sequencing was performed on RNA extracted from the proband's blood. Four different sizes of transcripts were found: wild type, r.7806_7874del , r.7806_7976del and r.7806–8_7806-lins. The latter 3 aberrant transcripts were not found in the 30 controls therefore polymorphism is unlikely. The r.7806–8_7806-lins transcript caused a frameshift which created a truncated protein; whereas the other two short transcripts produced shorter BRCA2 protein isoforms. Conclusion: We identified a novel BRCA2 VUS and classified it as pathogenic. Classification of VUS as neutral or pathogenic, particularly in ethnic groups where limited knowledge is known is a challenge. Research on the spectrum of mutations in diversed ethnic groups has important implications on management. [Genbank: DQ889340 ] No significant financial relationships to disclose.
Enhancing decision making for treatment options and active surveillance in prostate cancer.
Authors: Theresa Wicklin Gillespie, Jessica Lauren Rowell, Katharina V Echt, John Petros, Joseph Lipscomb, Laura Britan, Lindsey Allison Herrel, Michael Goodman
Journal: Journal of Clinical Oncology (2012)

e15187 Background: Prostate cancer (PCa), the most common malignancy among U.S. males, ranks second in tumor-specific mortality. African-Americans (AA) experience the highest rates of PCa mortality of any group. Many screen-detected PCa represent low-risk disease, and active surveillance (AS) may be a viable option in those cases; however, few men pursue AS. In December 2011, the NIH convened a State-of-the-Science Conference on the role of AS and issued a Draft Statement, highlighting knowledge gaps in treatment decision-making (DM) about AS. The purpose of this study was to determine strategies to enhance DM by men and their significant others (SO) about AS and other PCa therapies. Methods: This mixed methods design study (N=402, enrolled 2010-2011) investigated DM by men (N=204; 68% AA) with normal screening PSA and their SO (N=181; 65% AA) from 5 sites nationwide-51% from rural areas. Each site hosted 6 male and 6 SO focus groups. Data reported here include participant ranking of preferred source(s) for information about PCa therapies, including AS, and desired amount of treatment DM guidance. Results are from quantitative questionnaires analyzed using Fisher’s exact test, accompanied by two-sided p values, and qualitative data analysis utilizing Nvivo8. Results: A greater proportion of participants who were AA (62% vs 36%, p&lt;0.0001), those with lower health literacy (60% vs 47%, p=0.0144), and those self-identifying as having lower income levels (55% vs 43%, p=0.0372) preferred the primary care physician (PCP) vs. specialists or other health care providers as the main resource for DM related to AS and PCa. Qualitatively, PCPs were compared to “quarterbacks” who can solicit and coordinate information from the “whole team”. Over 90% of respondents overall indicated they would prefer major DM guidance (4/5 on scale of 1 to 5) from providers. Acceptance of AS as a treatment strategy was accompanied by themes of worry, insufficient provider-specific information, uncertainty, and need for care coordination. Conclusions: Men and their SO have important needs and preferences related to PCa DM in general, but AS in particular. Critical to better informed DM is more effective communication with providers, coordinated by an engaged PCP.
Planned interim analysis of the intergroup FFCD-GERCOR-FNCLCC-AERO phase III study comparing two sequences of chemotherapy in locally advanced or metastatic gastric cancers
Authors: R. Guimbaud, O. Bouché, C. Rebischung, F. Bonnetain, C. Louvet, F. Viret, T. André, E. Samalin, J. Gorent, J. Dutel, L. Bedenne
Journal: Journal of Clinical Oncology (2009)

4533 Background: There are several standard chemotherapies in locally advanced or metastatic gastric or cardia adenocarcinoma, including ECF. Methods: Patients (pts) with a gastric or cardiac adenocarcinoma, locally advanced or metastatic, not surgically curable, with a WHO PS ≤2 and evaluable or measurable lesions, were randomized (1:1) according to the following sequences: ECC (epirubicin 50 mg/m 2 D1+ cisplatin 60 mg/m 2 D1 + capecitabine 2000 mg/m 2 D2 to D15, every 3 weeks) in 1st line, then FOLFIRI (IRI 180 mg/m 2 D1, leucovorin 400 mg/m 2 D1, bolus 5FU 400 mg/m 2 D1 and continuous 5FU 2400 mg/m 2 in 46h, every 2 weeks) in 2 nd line (Arm A) vs the reverse sequence (Arm B) with a stratification for center, PS, adjuvant treatment, site, linitis and measurable disease. To show an improvement in median time to treatment failure for the 1 st line (TTF: time between randomization and progression, or treatment discontinuation or recurrence or death) of 15 to 20 weeks for arm B (α bilateral 5%; β 20 %), 381 failures and 416 pts are required in 4-year period. An interim analysis is planned when at least 190 failures are observed (ITT). TTF is estimated according to the Kaplan Meier method and compared with a Log-rank test. Results: In arm A and B, 174 and 175 pts were included respectively, between 17/06/05 and 21/12/07. Pts characteristics are: PS 1: 51%, med. age 60 years, gastric 67%, M+ 88%, resected primary tumor 27% and linitis 23%. In arms A and B respectively, 141 and 147 pts received at least one dose in 1 st line and 61 and 44 pts in 2 nd line. Toxicities during the first line is more frequent in the ECC than in the FOLFIRI arm: grade 3/4 (88 vs 68% - p ≤0.0001) and grade 3/4 hemato toxicities (69 vs 36% - p ≤0.001). In 2 nd line, toxicities frequency is not different in both arms. The median TTF in 1 st line (n = 310 pts) is 4.7 months [3.8 - 5.7] for ECC and 5.2 months [4.4–6.0] for FOLFIRI (Log Rank p = 0. 78). Regarding the 252 failures observed (67% of the required events), the significance level to reject H0 is p = 0.012 (EAST V5). Conclusions: It is not possible yet to conclude to the superiority of FOLFIRI in 1st line; the final analysis after observation of 381 failures is required. Regarding toxicity, hemato-toxicity is more frequent with ECC in 1st line. [Table: see text]
Private Equity Investment in Health Care—Reply
Authors: Suhas Gondi, Zirui Song
Journal: JAMA (2019)

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Induction chemotherapy (ICh) followed by concurrent chemoradiotherapy (ChR) in locally advanced squamous cell carcinoma of head and neck (SCCHN): Experience in a Mexican institute.
Authors: Miguel Angel Alvarez Avitia, Jose Luis Aguilar Ponce, Gisell Anaid Lara, Violeta Moreno Molina, Jaime G. De La Garza, Martin Granados-Garcia, Juan Cruz M, Andres Moran Mendoza, Abraham Ruiz
Journal: Journal of Clinical Oncology (2013)

e17031 Background: ICh has taken an important role in the treatment of locally advanced disease, but it has not been recognized in which patients (pts) may be the best option ICh followed by ChR or just ChR. We present our experience with ICh followed by ChR regimen in the National Cancer Institute of Mexico (INCan). Methods: We identified 69 patients (pts) diagnosed with locally and/or regionally advanced non-metastatic squamous cell cancer of head and neck, who were attended at the INCan from 2008-2012, in whom, the original treatment was ICh with two cycles of Paclitaxel (P), cisplatin (C) and 5Fluorouracil (5FU) scheme, followed by concurrent ChR with C. But only 35 pts of the original group accomplished the treatment. Results: 13 pts were women (37%) and 22 were men (63%).The median age at diagnosis was 59 years old. In stages III (28%), IVa (46%), and IVb (26%); AJCC, 2002. The subsites per pts. studied were: oral cavity 9 (25.7%), larynx 9 (25.7%), hypopharynx 7 (20%), paranasal sinuses 7 (20%) and oropharynx 3 (8.6%). The rate response was observed in 83%: complete objective rate response (CR) in13 pts (37%), partial response rate in 16 pts (46%) and progression rate in 6 pts. (17%). The mean survival was of 18.3 months (mth) (CI-95: 0.32-0.68).Median survival was not achieved in pts with CR with a median follow up of 2 yrs, pts with PR had a median survival of 15 mth (CI-95: 0.27-0.75) and the median progression was 11 mth (CI-95: 0.11-0.80). We have not got any CR with ICh only, but 13 patients obtained CR at the end of the ChR. Neither age, sex nor subsites were crucial to the clinical response. Conclusions: Our results cannot distinguish patients who might benefit from ICH. In the intention-to-treat population, more than a half of pts did not complete the proposed scheme. Recently, we reported a study using an alternative scheme: Cisplatin and gemcitabine concurrent with radiotherapy to treat pts with advanced SCCHN, and we found that this scheme of treatment is effective and well tolerated, with a 5 yr progression-free survival rate of 27.8 (CI-95: 0–61.5). Yet further studies are needed to compare ICh followed by RCh vs RCh to assess what the best treatment may be.
Image Gallery: Jacquet papulo‐erosive dermatitis in an adult
Authors: A.‐S. Darrigade, B. Milpied, J. Seneschal
Journal: British Journal of Dermatology (2019)

Funding sources: no external funding. Conflicts of interest: none to declare. Dear Editor, A 58‐year‐old man presented with scrotal ulcers that had appeared 10 days earlier. The patient was in severe social difficulties, had memory defect, praxis disorders and urinary incontinence. Clinically, ulcers were well‐demarcated, deep with elevated borders and slightly fibrinous (a,b, initial lesions). Common causes of genital ulcers were excluded and the skin biopsy showed a regenerative tissue. A diagnosis of Jacquet papulo‐erosive dermatitis was made. This entity has been mainly described in children representing a rare form of severe diaper dermatitis1 and is observed rarely in adults. The patient was treated with local ointment, petrolatum, daily toilet and the ulcers completely healed in 4 weeks (c, post‐treatment). ...
Abstract 17412: Paracrine Role of B Lymphocytes in Successful Bone Marrow Cell Therapy for Myocardial Infarction
Authors: Xiaoyin Wang, Hilda J Rodriguez, Melissa A Ruck, Kirstin Aschbacher, Michelle L Hermiston, Matthew L Springer
Journal: Circulation (2015)

Introduction: Treatment of myocardial infarction (MI) with bone marrow cells (BMCs) or cell-free BMC lysate substantially improves post-MI cardiac function in rodent experiments. However, clinical trials of BMC therapy have been less successful. While most mouse experiments use young healthy BMC donors, MI patients undergoing autologous cell therapy (i.e., receiving their own BMCs) are older and are post-MI. We have previously demonstrated that BMCs from aged and post-MI donor mice are therapeutically impaired, that donor MI induces inflammation leading to changes in BMC composition, and that BMCs from aged or post-MI mice have reduced levels of B cells, which reportedly can be a therapeutic BMC subpopulation. We recently observed that partial depletion of B cells from young healthy donor BMCs reduces the BMCs’ therapeutic effect, mimicking the effects of donor age or MI. Hypothesis: B cells play a crucial role in BMC therapy for MI, and B cell lysate is also therapeutic. Methods: We induced permanent coronary artery ligation MI, and implanted purified CD19+ bone marrow B cells from young healthy donors into the recipient infarct border zone 3 days post-MI via ultrasound guidance. CD3ε+ T cells and vehicle (HBSS) were injected as negative controls. A similar experiment was carried out with B cell lysate and T cell lysate. Results: In all groups, recipient left ventricular ejection fraction (EF) declined uniformly from baseline to day 2 post-MI, before cell injection. Injection of B cells significantly improved day 28 EF (p&lt;.0005 adjusted for multiple comparisons). In contrast, T cells provided little or no benefit relative to HBSS. Notably, B cell lysate, but not T cell lysate, increased EF comparably to intact B cells. *p&lt;.05 in figure. Conclusions: Bone marrow B cells play a crucial role in BMC therapy for MI via a paracrine mechanism. Reduction of bone marrow B cells by age or MI may explain why autologous BMC therapy in patients has not matched the success of rodent experiments.