tbuckley/cabot-search huggingface dataset:
Tandem high-dose chemotherapy with stem cell rescue followed by risk-adapted radiation in children with high-risk cerebral primitive neuroectodermal tumor: Results of the prospective SFCE-trial PNET HR+5.
Authors: Christelle Dufour, Marie-Bernadette Delisle, Anne Geoffray, Agnes Laplanche, Didier Frappaz, Celine Icher, Anne-Isabelle Bertozzi, Pierre Leblond, Francois P. Doz, Nicolas Andre, Pascale Schneider, Emilie De Carli, Claire Berger, Odile Lejars, Pascal B. Chastagner, Anne Pagnier, Christine Soler, Natacha Entz-Werle, Dominique Valteau-Couanet
Journal: Journal of Clinical Oncology (2014)

10007 Background: To assess the 3-year progression-free survival (PFS) rate of patients with newly diagnosed high-risk medulloblastoma (MB) or supratentorial primitive neuroectodermal tumor (sPNET) between 5-20 years treated according to the prospective multicenter trial PNET HR+5. Methods: Children received as postoperative induction chemotherapy two cycles of etoposide (500mg /m²) - carboplatine (800mg/m²), followed by two courses of thiotepa (600mg/m² per course) with autologous stem cell rescue. Risk-adapted conventional radiotherapy (RT) was delivered around day 45 after second transplantation. Craniospinal RT dose was 36 Gy for patients with metastatic disease or with unfavourable histology (anaplastic MB, large cell MB, MB with myc amplification) followed by a tumor bed boost of 18 Gy. Patients with localized sPNET received focal RT at the dose of 54 Gy. Maintenance treatment with 6 cycles of temozolomide was planned to start between 1-3 months after the end of RT. Results: From January 2009 to February 2012, 64 patients (MB=51; sPNET=13) between 5 and 19 years (median age, 9 years) were enrolled. Five patients didn’t received RT due to progressive disease. Maintenance treatment was administered in 44 patients. The median follow-up was 32 months (range, 16-54 months). The 3-year PFS and overall survival (OS) were 80% (95% CI: 68-88%) and 85% (95% CI: 74-92%), respectively. The 3-year PFS was 79% (95% CI: 65-88%) for children with MB and 85% (95% CI: 58-96%) for those with sPNET. No major unexpected toxicities and no treatment-related deaths were reported. Conclusions: This treatment based on high-dose chemotherapy and conventional RT resulted in a high overall survival rate in children and adolescent with newly diagnosed high-risk cerebral PNET. Clinical trial information: NCT00936156.
Impact Of Consolidation With Bortezomib-Thalidomide-Dexamethasone (VTd) Upfront In Multiple Myeloma (MM) With Partial Response (PR) At Completion Of Induction With Vtd
Authors: Xavier Leleu, Guillemette Fouquet, Benjamin Hebraud, Sylvain Garciaz, Anne-Marie Stoppa, Murielle Roussel, Denis Caillot, Marie-Lorraine Chretien, Bertrand Arnulf, Raphael Szalat, Laurent Garderet, Lina Benajiba, Brigitte Pegourie, Caroline Regny, Bruno Royer, Alexis Caulier, Cyrille Touzeau, Benoit Tessoulin, Jean Paul Fermand, Thierry Facon, Michel Attal, Herve Avet-Loiseau, Philippe Moreau
Journal: Blood (2013)
Reducing radiotherapy delays after surgery for breast cancer in five radiotherapy departments
Authors: S. P. Woynar, P. Burban, E. Le Prisé, P. Romestaing, C. Maylin, V. Mazeau, M. Cauterman, V. Vendrely
Journal: Journal of Clinical Oncology (2007)

17011 Background: An interval superior to 8 weeks between surgery and radiotherapy increases the risk of recurrence for patients with early stage breast cancer treated with conservative surgery and breast irradiation and without chemotherapy. Five French radiotherapy departments launched simultaneously a quality improvement project aimed at reducing the delay to radiotherapy for all types of cancers concerned. Breast cancer radiotherapy delays were used as the principal proxy to evaluate overall progress. Methods: Teams focused their efforts on reducing the interval between the first appointment with the radio-oncologist and the start of the radiotherapy, interval on which they had control. Between May and December 2005, consultancy firms financed by the Ministry of Health, helped the teams (radio-oncologists, physicists, radiographers and nurses) to realize an organizational audit: identifying the processes of treatment, analysing the patient flow and the staff and equipment capacity. Concerning breast cancer, target intervals were set based on the 8 weeks standard. An action plan that included matching capacity and demand (better allocation of staff time during the week), standardising treatment processes and patient programming was implemented between January and December 2006. Results: The five radiotherapy departments reduced the delays to radiotherapy for breast cancers as well as for the majority of the other cancer types. Concerning breast cancer, the average of the five departments intervals between the first appointments and the start of the radiotherapy dropped from 4.9 weeks to 2.3 weeks, reducing in the same time the interval between surgery and radiotherapy. Furthermore, the teams’ cohesion, motivation and sense of responsibility increased, key elements for the sustainability of the improvements. These results were obtained without an increase of the departments resources. Conclusion: By redesigning their organisation with a patient centred goal, the five radiotherapy departments were able to meet the standards of practice. Following these results, ten new departments have joined the program financed by the Ministry of Health. No significant financial relationships to disclose.
Abstract 15483: Red Cell Distribution Width as an Independent Predictor of Exercise Intolerance and Ventilatory Inefficiency in Patients with Chronic Heart Failure
Authors: Jong-Chan Youn, Sung-Jin Hong, Sungha Park, Sang-Hak Lee, Yangsoo Jang, Seok-Min Kang
Journal: Circulation (2012)

Background: Peak oxygen uptake (peak VO2) and ventilatory efficiency (VE/VCO2 slope) have proven to be strong prognostic markers in patients with chronic heart failure (CHF). Recently, increased re...
Metastatic neuroblastoma (NB) to the central nervous system (CNS): Improved outcome with combined modality including 131-I-8H9 or 131-I-3F8 radioimmunotherapy (RIT) delivered through the cerebrospinal fluid (CSF)
Authors: K. Kramer, S. Modak, B. H. Kushner, M. Souweidane, S. Wolden, J. Humm, P. Zanzonico, P. Smith-Jones, S. Larson, N. Cheung
Journal: Journal of Clinical Oncology (2007)

2022 Background: NB metastatic to the CNS (NB-CNS) is difficult to control. We describe a salvage regimen incorporating intra- Ommaya RIT delivered to the CSF. Methods: 37 patients (pts) with NB-CNS (parenchymal masses and/or leptomeningeal [LM] carcinomatosis) treated at MSKCC from 1988 through 2006 were reviewed. Nine (group #1) of 37 pts developed NB-CNS metastasis (median age 3.8 years) and were treated with a salvage regimen: resection of parenchymal masses, 2160 cGy craniospinal irradiation (CSI), intravenous irinotecan and oral temozolomide, and RIT with 131 I-8H9 and or 131 I-3F8 targeting tumor associated antigens on phase I/II studies. Immunotherapy (intravenous anti-GD2 monoclonal antibody 3F8 plus subcutaneous GM-CSF) was also given for systemic control. Survival was compared to the other 28 (group #2) pts who developed NB-CNS (median age 4.2 years) treated with combinations of surgery, chemotherapy, and radiation but without CSI + RIT. Results: All 37 pts had high risk disease at initial diagnosis of NB. 9 of 9 group #1 pts had marrow and/or bony involvement; 6 of 9 had MYCN amplification and 5 of 9 had serum LDH &gt;1500 U/ml. All had intensive chemotherapy and radiotherapy prior to CNS relapse. Despite this, the CNS salvage regimen was well-tolerated. Myelosuppression following CSI and chemotherapy was common; 2 pts received stem cell support. All 9 pts in the RIT group are alive and well, disease-free at 3+, 11+, 15+, 18+, 18+, 20+, 22+, 31+, 42+ months since CNS relapse. In contrast, pts in group #2 had a median time to death of 5.5 months, (p&lt;0.0001) for survival by Kaplan-Meier analysis. Conclusion: Similar to CNS metastases in most other solid tumors, conventional therapies have been ineffective for NB-CNS. The addition of RIT using 131 I-3F8 or 131 I-8H9 is well-tolerated and improves the prognosis for these high risk patients. No significant financial relationships to disclose.
A unique microRNA signature associated with nucleophosmin mutations in normal karyotype acute myeloid leukemia
Authors: R. Garzon, S. Volinia, B. Falini, C. M. Croce
Journal: Journal of Clinical Oncology (2007)

7015 Background: Nucleophosmin (NPM) mutations are present in about 30 to 50 % of the patients with normal karyotype acute myeloid leukemia (NK-AML). The mutant NPM protein shows aberrant cytoplasmic location and is frequently associated with FLT3 mutations. Little is know, however how NPM mutants promote leukemia. To obtain insights about the biology of NPM+ AML we investigated the expression of microRNAs in NK-AML patients characterized for NPM mutations. Methods: We studied 85 adult NK-AML patients characterized for NPM, FLT3 ITD and FLT3 D835 mutations using a miRNA microarray platform containing 345 mature and precursors miRNAs. Mutation analysis for NPM, FLT3 ITD and FLT3 D835 were carried out in most of the patients as previously described (Falini, Blood 2006). The distribution of the mutations were as follows: NPMc+ (54 patients), NPMc- (31), FLT3 ITD+ (27), FLT3 ITD-(51) and FLT3 D835+ (21) and FLT3 D835-(26). Data were analyzed after background subtraction and normalization with a set of housekeeping genes using Significance Analysis of Microarrays and Predictive Analysis of microarrays. The results were validated using miRNA q-RT-PCR. Results: We identified a strong miRNA signature that distinguishes NPMc+ cases with high accuracy and includes the up-regulation of miR-10a, miR-10b and several let-7 family members. Many of the down-regulated miRNAs including miR-134, miR-194, miR-204, miR-526 and miR-28 are predicted to target many HOX genes suggesting that NPM mutants may induce HOX genes through the down-modulation of miRNA regulators of these genes. The signatures associated with FLT3 mutations were not accurate to predict this abnormality. However, when we analyzed the subgroup of NPMc+ FLT3 ITD + cases a distinctive signature was found with respect to other NPMc+ FLT3 negative cases. Conclusions: A unique miRNA signature is associated with NPMc+ mutations in AML. FLT3 ITD and FLT3 D835 are not clearly associated to any characteristic miRNA signature when analyzed individually. However the subgroup of NPMc+ FLT3 ITD has a distinctive miRNA signature. This data provide with new insights about the pathogenesis of NPMc+ AML that could be exploited to generate novel therapeutic strategies for one of the most common mutations in AML. No significant financial relationships to disclose.
Progression-free survival (PFS) as a new endpoint for designing phase II trials in patients with refractory germ cell tumors (GCT).
Authors: D. R. Feldman, S. Patil, M. J. Trinos, M. Carousso, M. S. Ginsberg, J. Sheinfeld, D. F. Bajorin, G. J. Bosl, R. J. Motzer
Journal: Journal of Clinical Oncology (2010)

4583 Background: Refractory GCT patients have a poor prognosis and limited treatment options. Identification of novel active agents is a priority but may be impaired by use of response as the main endpoint in phase II trials. Improved endpoints may hasten the development of new effective agents. Methods: We retrospectively reviewed the characteristics and outcome of refractory GCT patients enrolled in 7 single-agent phase II trials conducted at MSKCC between 1990 and 2008. Study agents included: suramin, all- transretinoic acid, topotecan, pyrazoloacridine, temozolamide, ixabepilone, and sunitinib. For patients treated on more than 1 study, baseline characteristics and outcome to the first trial therapy were used. The major endpoints evaluated were response, PFS, and overall survival (OS). Results: 90 patients (M:F 87:3) were treated, including 4 patients enrolled on more than 1 study. The median age was 35 (range 17-64) and primary tumor site was testis in 65, mediastinum in 17, retroperitoneum in 4, and other in 4. 86 patients had non-seminoma and 4 had pure seminoma. Best responses were 1 (1%) partial response (ixabepilone), 15 (17%) stable disease, and 74 (82%) progressive disease. Median PFS and OS were 1.0 month (95%CI: 0.8-1.3) and 4.7 months (95%CI: 3.5-6.4), respectively. 86 patients died; of the remaining 4 patients, 1 was rendered disease-free by salvage resection of a lung nodule, 1 achieved a durable complete response to single agent paclitaxel, and the other 2 have been lost to follow-up. The 12- and 16-week PFS rates were 9% and 6% respectively. Conclusions: Patients with refractory GCT progress rapidly when treated with ineffective agents. PFS may be a useful endpoint for designing phase II trials testing novel agents in this population. A 12-week PFS endpoint (with comparison to the 9% benchmark rate reported herein) is recommended. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Lilly, Pfizer Bristol-Myers Squibb, Genentech, Lilly, Pfizer
Induction (Ind), gemcitabine (G), docetaxel (D) and cisplatin (C) plus concurrent (Con) chemotherapy with thoracic radiotherapy (TRT) in stage III non-small cell lung cancer (NSCLC)
Authors: S. de Santis, V. Donato, C. Caruso, M. R. Migliorino, B. Tedesco, R. Belli, S. Valentino, F. De Marinis
Journal: Journal of Clinical Oncology (2008)

7589 Background: New Phase III Intergroup Trial RTOG 0412 was testing induction chemoradiotherapy with cisplatin and docetaxel followed by surgical resection in stage IIIA N2. Our Institution demonstrated in a phase I study that the doses of induction chemotherapy GDC triple are D (30 mg/m2), C (35 mg/m2) and G (1,000 mg/m2) every 3 weeks. In present phase II trial we evaluated toxicity and activity of GDC Ind plus Con with TRT in stage III NSCLC. Methods: Chemotherapy-naïve pts with stage IIIA-N2 and IIIB (T4, N1-N2 only, except malignant pleural effusion) NSCLC were eligible. All drugs, G (1,000 mg/m2), C (35 mg/m2), D (30 mg/m2), were given on days 1 and 8, q21 days up to 2 cycles followed by Con: for stage IIIA, N2 non-bulky C 50 mg/m2 on days 1 and 8 q21 days for 2 cycles, and D 20 mg/m2/week x5; for stage IIIA N2 bulky and IIIB, C 50 mg/m2 on days 1 and 8, and etoposide 50 mg/m2 day 1 through 5, q28 days for 2 cycles. Patient with resectable disease at reevaluation after TRT 45 Gy on T and N fields, underwent surgical resection. Otherwise completed TRT (uninterrupted) till to 61,2 Gy. Results: From Jan ‘06 to Sep ‘07 43 eligible pts were enrolled. The characteristics were: median age 58 years (range 40–75), male/female ratio 32/11, 8 pts never smokers, stage IIIA N2 non-bulky/N2 bulky/IIIB 6/14/23. All pts had ECOG PS 0–1 at study entry. Histology was: 10 adenocarcinoma, 17 squamous-cell, 14 undifferentiated and 2 with mixed histology. 60% of 42 evaluable pts for response had an OR after Ind. Nineteen responding patients, including 9 IIIB cases and 10 IIIA, underwent radical surgery. The pathologic CR rate in the mediastinal lymph nodes has been obtained in 58%. Fourteen patients (33%) were not resectable and received full dose TRT. Ind therapy was well tolerated with 7 pts experiencing disease progression. Gr 3 toxicities during Con therapy were anemia (15%), neutropenia (16%), esophagitis (9%), fatigue (9%). The PFS and MST are not mature enough to estimate as only 14 deaths have occurred. Conclusions: These preliminary data suggest that this Ind chemotherapy and Con chemoradiotherapy regimens are active and well tolerated in locally advanced NSCLC. Response to induction chemotherapy may have major prognostic significance. No significant financial relationships to disclose.
Routine versus clinically indicated post-treatment surveillance in head and neck cancer.
Authors: N. M. Iyengar, J. K. Salama, K. Stenson, D. J. Haraf, E. A. Blair, E. E. Vokes, E. E. Cohen
Journal: Journal of Clinical Oncology (2010)

5601 Background: Recurrence surveillance practices in post-therapy head and neck cancer (HNC) patients vary widely with no established standard of care. Published guidelines recommend conflicting frequency and methods by which to detect recurrence. We describe our experience with post-therapy screening by computed tomography (CT) in a multicenter setting. Methods: 345 patients at 5 centers with stage II through IV squamous cell HNC were treated by curative intent with chemoradiation therapy. All patients underwent routine post-therapy CT surveillance. Treatment failure was identified by routine detection (RD) or by additional clinical detection (CD) not found by routine surveillance. We retrospectively analyzed the impact of RD versus CD on subsequent treatment plan and clinical outcomes. Results: 56 patients were found to have pathologically confirmed tumor recurrence. 30 of these patients continued to receive care at an associated center with available follow-up data; 16 were identified by CD and 14 by RD. 12 patients (86%) in the RD group were initially diagnosed with stage IV HNC versus 9 patients (56%) in the CD group. After initial therapy, 8 patients (57%) in the RD group and 10 patients (63%) in the CD group achieved complete radiographic response. The average number of months to detection of therapy failure was 8.5 (median 7) and 17 (median 6.5) in the RD and CD groups, respectively. The average number of post-therapy CT scans in both groups was similar: 3 in the RD group and 4 in the CD group, out of which an average of 3 were done by routine surveillance. Distant metastases were identified more frequently in the RD group. Of patients with stage IV HNC, 5 (36%) in the RD group and 7 (44%) in the CD group planned for further therapy. Treatment of recurrence in less aggressive HNC was also similar in both groups. Tumor recurrence portended poor survival in both groups with no statistically significant difference - 12 patients (86%) in the RD group and 9 patients (56%) in the CD group died from HNC (p = 0.17). Conclusions: Recurrence in stage IV HNC was identified more frequently and earlier by routine surveillance, but treatment and survival patterns in this subgroup were similar whether detected by routine or clinically-indicated radiography. No significant financial relationships to disclose.
Importance of time-related factors on outcome in patients treated with surgery and postoperative radiation therapy for locally advanced squamous cell carcinoma of head and neck
Authors: C. Le Tourneau, M. Velten, G. M. Jung, G. Bronner, H. Flesch, C. Borel
Journal: Journal of Clinical Oncology (2005)

5542 Background: To determine the effect of treatment time-related factors on outcome in patients treated with surgery and postoperative radiation therapy (RT) for locally advanced squamous cell carcinoma of head and neck (SCCHN). The site of the primary tumor was the buccal cavity (38), the oropharynx (151), the larynx (24) and the hypopharynx (95). Univariate and multivariate analysis were performed. Methods: A retrospective study was performed on 308 consecutive patients treated from 1990 to 1998 with surgery and postoperative RT (>= 55 Gy) for SCCHN. Time-related factors considered were interval from surgery to the start of RT, RT duration and total time from surgery to completion of RT (total treatment time). Other variables considered were pT and pN stages, margin status, capsule rupture, tumor site, age and gender. Results: Median follow-up was 36 months. From univariate analysis of overall survival (OS), statistically prognostic factors were pT (p<0.0001) and pN (p=0.008) stages, RT duration (p=0.01), total treatment time (p=0.02) and age (p=0.01). OS at 5 years were 42% and 27% respectively when total time treatment was under and over 100 days. OS at 5 years were 43% and 28% respectively when RT duration was under and over 52 days. Nevertheless, time- related factors were not associated with locoregional control and metastase free survival (MFS) in univariate analysis. From multivariate analysis, only the interval from surgery to the start of RT (p=0.03) was an independent time related factor for MFS. Conclusions: Our results indicate that a short total treatment time and a short RT duration is associated with improved OS. No significant financial relationships to disclose.
Polysomnographic measures of sleep moderate the relationship between depression and pain
Authors: K. P. Parker, D. L. Bliwise, J. Dalton, W. Harris, S. Jain, M. Kohles-Baker, M. Ribeiro, C. Vena, B. Viswanathan
Journal: Journal of Clinical Oncology (2006)

8526 Background: We explored the effects of polysomnographic measures of nocturnal sleep on depression and pain in advanced cancer patients taking opioids. Methods: The sample included 72 subjects (solid tumor, Stages III/IV) with a mean age of 55.9 (9.1); 39 were male. All were taking opioids. Subjects underwent ambulatory polysomnography for 48 hours in their homes. Nocturnal sleep parameters included total sleep time (minutes); sleep efficiency (SE; %); sleep latency (SL; minutes); rapid-eye-movement sleep latency (REML; minutes); the percentages (%) of non-rapid eye movement (NREM) Stages 1, 2, and slow wave sleep (SWS, 3 &amp; 4), and REM sleep; and the number of awakenings &gt; 60 seconds. Subjects kept an opioid diary, data from which were converted into a mean hourly morphine equivalent dose (HMED). Subjects also completed the Brief Pain Inventory (BPI) and the Beck Depression Inventory (BDI). Descriptive, correlation, and regression procedures were used for data analysis. Results: Subjects had a mean nocturnal sleep period of 400.1 ± 97.4 minutes. The SL was normal at 26.5 ± 42.6 minutes but the SE was low (77.5 ± 13.2%). Most sleep was light NREM Stages 1 and 2 with decreased amounts of deep SWS (0.3 ± 2.7%) and REM sleep (14.4 ± 8.5%). The REML was prolonged at 149.1 ± 105.1 minutes. The mean BPI scores for pain intensity and interference were 4.4 ± 1.4 and 5.0 ± 2.1, respectively. The mean BDI score was 13.7 ± 7.9. The average HMED was .59 ± .1. Controlling for age and gender, regression analyses revealed that SWS and REM sleep moderated the relationship between depression and pain. Those with more SWS had lower depression levels in spite of higher pain intensity (t = -2.8, p = .007) while those with more REM sleep had lower depression levels despite higher pain interference (t = -2.0, p = .045). Controlling for pain intensity and interference, HMED was positively associated with Stage 1 % (r = .36, p = .001) and the number of nocturnal awakenings &gt; 60 seconds (r = .28, p = .019). Conclusions: Opioids may lighten and disrupt sleep altering sleep cycle progression. The resulting decrements in SWS and REM sleep may lead to increased depression and enhanced pain. Consideration of the timing and dosing of opioids in relationship to nocturnal sleep may decrease depression and subsequently optimize pain management. No significant financial relationships to disclose.
FOXA1 and PR predict ipsilateral event risk and identify a group with strong radiation response in ductal carcinoma in situ (DCIS)
Authors: Steven P. Linke, Troy M. Bremer, Pat Whitworth, Aflred Lui, Jess Savala, Yelina Noskina, Todd Barry, Stephen Lyle, Stephanie C. Walters, Cherie Taglienti, Karl Simin, Wenjing Zhou, Karin Jirstrom, Rose-Marie Amini, Fredrik Warnberg
Journal: Cancer Research (2015)

FOXA1 and PR predict ipsilateral event risk and identify a group with strong radiation response in ductal carcinoma in situ (DCIS)
Early decrease of serum biomarkers of type II collagen degradation (Coll2-1) and joint inflammation (Coll2-1NO2) by hyaluronic acid intra-articular injections in patients with knee osteoarthritis
Authors: Yves Henrotin, T Conrozier, Michelle Deberg, A Walliser-Lohse, P Richette, D Mulleman, B Maillet, F Rannou, C Piroth, P Hilliquin, E Vignon, X Chevalier
Journal: Annals of the Rheumatic Diseases (2011)