tbuckley/cabot-search huggingface dataset:
Usefulness of denosumab to nonsquamous non-small cell lung cancer patients with bone metastases.
Authors: Hibiki Udagawa, Seiji Niho, Keisuke Kirita, Shigeki Umemura, Shingo Matsumoto, Kiyotaka Yoh, Hironobu Ohmatsu, Koichi Goto
Journal: Journal of Clinical Oncology (2015)

9609 Background: Denosumab reduces the incidence of the skeletal-related events (SRE) in patients with bone metastases (BM) from solid tumors. However, there have been no detailed reports about the efficacy of Denosumab to the untreated non-squamous non-small cell lung cancer (NSCLC) patients with BM. Methods: The medical records of patients less than 75 years of age, with BM from non-squamous NSCLC and treated with platinum-doublet or EGFR-TKI as 1st-line systemic chemotherapy at our institution from May 2010 to April 2014 were retrospectively reviewed. The overall survival (OS), progression-free survival (PFS) of platinum-based chemotherapy and/or EGFR-TKI and time to SRE (radiation or surgery to bone, spinal cord compression or pathologic fracture) were analyzed according to the treatment for the BM (Denosumab, Zoledronic Acid or no treatment). Results: A total of 149 patients were eligible. Fifty-two patients received Denosumab (Dmab-group), 51 received Zoledronic Acid (ZA-group) and 46 did not receive the treatment for the BM (Non-group). The frequency of the prior SRE in the Non-group was lower than the Dmab-Group and ZA-group (21.7%, 44.2% and 43.1%, respectively), but there was no difference of other clinicopathological characteristics among 3 groups. The OS in the Dmab-group was significantly longer than that in the ZA-group or Non-group (25.4 months vs 13.9 months, 11.2 months, respectively; p = 0.01). In the multivariate analysis, Dmab-group was significantly associated with a favorable survival [vs ZA-group; p < 0.01, HR 0.365 (95 %CI, 0.209-0.621). vs Non-group; p < 0.01, HR 0.388 (95%CI, 0.213-0.691)]. The Dmab-group showed significantly longer PFS for patients treated with platinum-based chemotherapy than the ZA-group or Non-group (5.1 months vs 3.3 months, 4.3 months, respectively; p = 0.046). No significant difference in the PFS for patients treated with EGFR-TKI or time to SRE was observed among 3 groups. Conclusions: Our results suggest that Denosumab may improve overall survival compared with Zoledronic Acid or no treatment for BM in patients with non-squamous NSCLC and BM.
Analysis of the contemporary use of high-dose chemotherapy (HDCT) in germ cell tumors (GCT) in Europe: Early findings of an ongoing EBMT-sponsored study.
Authors: Andrea Necchi, Manuela Badoglio, Rosalba Miceli, Jean-Henri Bourhis, Daniele Laszlo, Emmanuelle Nicolas-Virelizier, Patrick Wuchter, Peter Dreger, William Hermann Kruger, Ali Unal, Antonio Campos, Juan Montoro, Daniele Raggi, Patrizia Giannatempo, Alessandro M. Gianni, Paolo Pedrazzoli, Francesco Lanza
Journal: Journal of Clinical Oncology (2014)

e15536 Background: HDCT with CD34+ cell rescue is steadily utilized in GCT worldwide, as its role in the salvage setting has been recognized. The most effective regimen was carboplatin and etoposide (CE) for 2-3 courses. To explore patterns of care/outcomes in “real world” patients (pts), we initiated a retrospective study in the EBMT network. Methods: Data were collected so far from 9 European centers. Eligibility included adult males and females with GCT, treatment with HDCT and CD34+ cell rescue. The study was limited to the years 2002-2012. A subset of pts with complete data on prognostic factors (IGCCCG category, line of HDCT [2nd vs >2nd], response to induction prior to HDCT, and regimen) was subjected to regression analysis. Results: By 10/2013, 185 pts have been enrolled. Median age was 31 years (IQR: 26-39), 176 were male, 9 female. 152 pts (82%) required one mobilization attempt, 28 pts (15%) two, and the remaining three. 21 different mobilization regimens were used. All pts mobilized with GCSF (14 with GCSF only without CT), and 9 (4.8%) required the use of plerifaxor. Median number of CD34+ cells infused per transplant was 3.6x10^6/Kg (IQR: 2.6-6). 15 different HDCT regimens were administered as single (n=64), double (n=60), or triple (n=61) courses. The multivariable analysis for PFS in a subset of 63 patients with full available data revealed that salvage HDCT regimen trended for significance in favor of ICE (ifosfamide, carboplatin, etoposide; HR: 0.95, 95%CI, 0.92-4.14, p=0.080) and was significant for OS (HR: 2.88, 95%CI, 1.11-7.51, p=0.030). Progressive disease prior to HDCT trended for significance for OS (HR: 2.26, 95%CI, 0.93-5.48, p=0.070). Among the 185 pts, exploratory univariable analysis for PFS/OS was not significant for HDCT regimen (p=0.084 and p=0.086). Two patients (1%) died for secondary leukemia. Conclusions: The contemporary use of HDCT in GCT in Europe is highly heterogeneous and harmonizing treatment pathway outside of clinical trials is an essential prerequisite to improve the outcome. The study is also aimed to register all prospective data on transplants in GCT and to validate the best HDCT regimen in a multinational setting.
CNS-directed chemotherapy including high-dose chemotherapy with autologous stem cell transplantation (HD-ASCT) for CNS relapse of aggressive lymphomas: Final analysis of a phase II study.
Authors: Agnieszka Korfel, Gerald Illerhaus, Mathias Haenel, Robert Moehle, Roland Schroers, Thomas Elter, Marcel Reiser, Martin H. Dreyling, Jan Eucker, Christian Winfried Scholz, Bernd Metzner, Alexander Roeth, Josef Birkmann, Uwe S. Schlegel, Peter Martus, Eckhard Thiel, Lars Fischer
Journal: Journal of Clinical Oncology (2012)

8031 Background: The outcome of patients with CNS relapse of aggressive lymphoma (secondary CNS lymphoma, SCNSL) is poor with no standard therapy established thus far. Here we present the final analysis of a prospective multicenter phase II study using an intensive induction regimen followed by high-dose chemotherapy and autologous stem-cell transplantation. Methods: Adult immunocompetent patients ≤65 years with SCNSL were eligible. Induction chemotherapy consisted of two cycles MTX/IFO (methotrexate 4g/m 2 iv. d1, ifosfamide 2g/m 2 iv. d3-5 and i.th. liposomal cytarabine 50mg d6) and one cycle AraC/TT (cytarabine 3g/m 2 d1-2, thiotepa 40mg/m2 iv. d 2 and i.th. liposomal cytarabine 50mg d3). Then, patients without progression received high-dose chemotherapy with carmustine 400mg/m2 iv. d -5, thiotepa 2x5mg/kg iv. d -4 to -3 and etoposide 150mg/m 2 iv. d -5 to -3 followed by ASCT d0. Results: Thirty eligible patients (median age 58 years) were enrolled. Three patients had T-cell and 27 aggressive B-cell lymphoma. Pre-treatment was CHOP-like in 29 patients, including rituximab in 26. CNS relapse occurred after a median of 8.5 (3-80) months and was intracerebral in 23 and meningeal in13 patients (combined in 7); 6 had concomitant systemic lymphoma. After induction therapy CNS response was found in 22 (73%) patients (8xCR, 14xPR), 3 patients had SD, 4 patients PD and 1 patient no response evaluation. HD-ASCT was performed in 24 patients; resulting in 15 CR (63%), 2 PR (8%) and 7 PD (29%). Myelotoxicity was the most frequent WHO grade 3-4 adverse event with infections in 8/30 pts on MTX/IFO (27%), 5/23 (22%) on AraC/TT and 11/20(55%) on HD-ASCT. One patient died due to septic diverticulitis and one developed persisting fecal incontinence. The median follow up was 21 months. The median PFS was 12.1 months (95% CI 6.4-17.7) in all patients and 30.4 (95%CI 2.5-58.3) months after HD-ASCT, the median overall survival was 27.4 months and not reached, respectively. Conclusions: This first prospective study on SCNSL demonstrates that lasting remissions can be achieved with CNS-directed HD-ASCT in a large proportion of patients and probably cure in some.
Sleep-disordered breathing in chronic heart failure is highly variable when measured remotely using a novel non-contact biomotion sensor
Authors: Kenneth McDonald, Rory O'Hanlon, Henry Oluwasefunmi Savage, Rami N. Khushaba, Michael Colefax, Steven Farrugia, Faizan Javed, Klaus Schindhelm, Ian Wilcox, Martin R. Cowie
Journal: European Journal of Heart Failure (2017)
Centralized independent disease status adjudication for maintenance treatment evaluation in advanced ovarian cancer setting: A critical analysis of the MIMOSA trial experience.
Authors: Simona Scartoni, Jacobus Pfisterer, Paul Sabbatini, Jonathan S. Berek, Monica Bertolotti, Mariapaola Contini, Goso Cristina, Isabella Otranto, Lorenzo Melani, Giulia Poggiali, Carlo Alberto Maggi, Angela Capriati, Cecilia Simonelli
Journal: Journal of Clinical Oncology (2013)

e16510^ Background: Progression free survival (PFS) is an accepted surrogate of Overall Survival (OS) often used as the primary endpoint in phase III trials evaluating maintenance treatment in advanced ovarian cancer (AOC). Methods: We compare the centrally assessed PFS (PFS-CA) vsthe locally assessed PFS (PFS-LA) data collected in the Mimosa Trial, a randomized, double blind, placebo controlled, Phase III study of Abagovomab maintenance therapy in AOC patients in complete response after standard chemotherapy. PFS was assessed at pre-fixed time points by pelvis/abdomen CT scan, which were centrally and blinded reviewed by trained radiologists for radiological assessment (RA) of recurrence status and date (PFS-RA). An independent blinded committee, including one radiologist and one oncologist, reviewed all the CT scans and any additional imaging records AND/OR clinical data (when locally required for patients’management) to adjudicate the recurrence status and date (PFS-CA). PFS-CA was used for the primary analysis; sensitivity analyses were carried out on PFS-LA as well as on the strictly defined PFS-RA data. Results: 888 patients were randomized 2:1 to receive Abagovomab or placebo. In the ITT population (n = 886) time to PFS-CA was 403 and 402 days in Abagovomab and placebo group, respectively; in the sensitivity analyses time to PFS-LA was 407 and 409, and finally time to PFS-RA was 414- 487 days respectively, without any statistically significant differences between groups or PFS assessments. Conclusions: No differences were seen in PFS assessed centrally or locally when RA and clinical data are considered, whereas a slightly longer PFS was observed when it was assessed exclusively by the independent radiological review although this is not statistically different. The centralised independent assessment of recurrence status for ovarian cancer patients treated in the remission setting appears not to add value to the local blinded assessment. Clinical trial information: NCT00418574.
R-CVP versus R-CHOP versus R-FM as first-line therapy for advanced-stage follicular lymphoma: Final results of FOLL05 trial from the Fondazione Italiana Linfomi (FIL).
Authors: Massimo Federico, Stefano Luminari, Alessandra Dondi, Stefano Sacchi, Vito Franco, Stefano Pileri, Marco Lombardo, Giuseppe Rossi, Luca Arcaini, Teodoro Chisesi, Mario Petrini, Sara Galimberti, Umberto Vitolo, Francesco Di Raimondo, Luigi Rigacci, Angelo Michele Carella, Francesco Angrilli, Roberto Freilone, Andres Ferreri, Maura Brugiatelli
Journal: Journal of Clinical Oncology (2012)

8006 Background: The optimal chemotherapy regimen for patients with advanced, active follicular lymphoma (FL) has not been established yet. We conducted a randomized trial comparing R-CVP with R-CHOP and R-FM. Methods: Previously untreated patients with advanced FL were randomly assigned to receive 8 doses of rituximab associated to 8 cycles of CVP, or 6 cycles of CHOP or FM (fludarabine 25 mg/m2 day 1-3, mitoxantrone 10 mg/m2 day 1). No maintenance therapy was allowed. The principal study end point was Time to Treatment Failure (TTF). Events in TTF were failure of induction therapy, progressive or relapse disease and death from any causes. In order to show a hazard ratio between each experimental arms and standard arm of 0.53 we planned to accrue 534 patients (178 per arm) with 4 years of accrual and 1 year of follow-up. Statistical tests were two-sided with an alpha error of 0.05, adjusted by Bonferroni for multiple arm comparison, and power of 90%. Results: Between March 2006 and September 2010, 534 patients were enrolled; 30 were subsequently excluded due to violation of inclusion criteria. Median patient age was 56 years (range 30-75), 63% of patients had stage IV disease, 37% had 3-5 FLIPI and 27% 3-5 FLIPI2 scores. At the end of induction treatment the overall response rate (CR+ PR) for the whole group was 91% (p=0.247). After a median follow-up of 34 months 208 events for TTF were recorded; 3-year TTF was 46%, 64% and 61% for patients treated with R-CVP, R-CHOP and R-FM respectively (R-CHOP vs R-CVP p=0.007; R-FM vs R-CVP p=0.021; R-FM vs R-CHOP p=0.969). The 3-year overall survival rate (OS) was 98%, 95% and 93% for R-CVP, R-CHOP and R-FM group, respectively (P=NS). Patients treated with R-FM had a higher rate of g III-IV neutropenia (64% vs 28% R-CVP, p&lt;0.001; and vs 50% R-CHOP, p=0.015). During follow-up second malignancies were registered as late events in 23 patients (2%, 3% and 8% in R-CVP, R-CHOP and R-FM, respectively). Conclusions: This trial showed that R-CVP was associated with an inferior 3-year TTF and PFS compared with R-FM and R-CHOP. OS was similar among study arms but R-FM showed a higher rate of secondary tumors.
Structural variations in mammary carcinomas and their detection in cell-free plasma DNA in a clinical dog model.
Authors: Silvia Hennecke, Kirsten Bornemann-Kolatzki, Howard B. Urnovitz, Stefan Neumann, Bertram Brenig, Ekkehard Schütz, Julia Beck
Journal: Journal of Clinical Oncology (2013)

1537 Background: Mammary tumors are the most frequent cancers in female dogs exhibiting a variety of histopathological differences to which a dearth of information about their genomic status exists. Massive parallel sequencing (MPS) of tumor, white blood cell and associated cell-free DNA from plasma revealed the utility of the dog in modeling the dynamics of cell-free cancer DNA. Methods: Five tumors of three different histological subtypes were evaluated. MPS of tumors was performed in comparison to the respective white blood cell DNA of each animal. Copy number and structural variations were evaluated and those only present in tumors were validated using digital droplet PCR (ddPCR). Results: Using mate-pair sequencing chromosomal aneuploidies were found in two tumors, frequent smaller deletions were found in one, inter-chromosomal fusions in one other, whereas noteworthy one tumor was devoid of any of these anomalies. The detected structural variations affect several known cancer associated genes such as BRCA1, cMYC, and KIT. One deletion of the proximal end of CFA27, harboring the tumor suppressor gene PFDN5 was detected in four of the five tumors. Using ddPCR, this deletion was validated and detected in 50% of tumors (N=20).One breakpoint specific ddPCRs was established for each of four tumors. In all cases tumor specific DNA was detected in the plasma prior to surgery and accounted for 1 to 24 % of the cfDNA. In one animal the ddPCR detected tumor specific DNA in cfDNA still present &gt;1 year after surgery; subsequently a lung metastasis was found as cause. Furthermore, paired-end sequencing of extracted cfDNA and subsequent depth of coverage analysis proved that copy-number variations of the tumor are reflected by the cfDNA. Conclusions: The similarities of patterns of copy-number imbalances (e.g. chromosomal and segmental aneuploidy subtypes) of canine and human mammary cancers and their correlation in cfDNA supports the use of the dog as a model for using MPS for screening and discovery of individual cancer biomarkers. The ddPCR technology offers rapid, cost effective and sensitive confirmation and monitoring. The possibility exists that ddPCR can be expanded to screening for common cancer related variants.
Preoperative hepatic and regional arterial chemotherapy in the prevention of liver metastasis after colorectal cancer surgery
Authors: J. Xu, Y. Zhong, W. Niu, X. Qin, Y. Wei, L. Ren, J. Wang, J. Chen, S. Qian
Journal: Journal of Clinical Oncology (2009)

4090 Background: To investigate whether preoperative hepatic and regional arterial chemotherapy are able to prevent liver metastasis and improve overall survival in patients receiving curative colorectal cancer resection. Methods: Patients with Stage II or Stage III colorectal cancer (CRC) were randomly assigned to receive preoperative hepatic and regional arterial chemotherapy (PHRAC group, n=256) or surgery alone (control group, n=253). The primary endpoint was disease-free survival, whereas the secondary endpoints included liver metastasis-free survival and overall survival. Results: There were no significant differences in overall morbidity between PHRAC and Control groups. During the follow-up period (median, 42 months), the median liver metastasis time for patients with stage III CRC was significantly longer in the PHRAC group (16±3 months v.s. 8±1 months, P=0.01). In stage III patients, there was also significant difference between the two groups with regard to the incidence of liver metastasis (18.9% vs 27.3%, P=0.01), 5-year disease-free survival (70.2% vs 52.0%, P=0.0076), 5-year overall survival (80.3% vs 69.5%, P=0.020) and the median survival time (40.1± 4.6 months vs 36.3 ± 3.2 months, P=0.03). In the PHRAC arm, the risk ratio of recurrence was 0.63 (95% CI, 0.51–0.79, P=0.0001), of death was 0.50(95% CI, 0.32–0.67; P=0.005), and of liver metastasis was 0.70 (95% CI, 0.52–0.86; p=0.01). In contrast, PHRAC seemed to be no benefit for stage II patients. Toxicities, such as hepatic toxicity and leucocyte decreasing, were mild and could be cured with medicine. Conclusions: Preoperative hepatic and regional arterial chemotherapy, in combination with surgical resection, could be able to reduce and delay the occurrence of liver metastasis and therefore improve survival rate in patients with stage III colorectal cancer. No significant financial relationships to disclose.
Utilidad de las endoprótesis esofágicas en el tratamiento de las complicaciones postquirúrgicas tras la esófago-gastrectomía parcial
Authors: C Huertas Nadal, TM Leyanira Del Valle, CL Rosales Alexander, M Albert Carrasco, H Uchima Hoecklin, M Hombrados Verde, M Figa Francesch, X Aldeguer Manté
Journal: Endoscopy (2015)

Introducción: La estenosis y/o dehiscencia postesofaguectomía se produce en un 4%-30%. La colocación de stents se acepta como terapia electiva aunque faltan estudios aleatorizados.
Erlotinib after initial platinum-doublet chemotherapy in patients with epidermal growth factor receptor (<i>EGFR</i>) wild-type (WT) non-small cell lung cancer (NSCLC): Results of a combined patient-level analysis of the BR.21 and SATURN trials.
Authors: Raymond U Osarogiagbon, Federico Cappuzzo, Tudor-Eliade Ciuleanu, Larry Leon
Journal: Journal of Clinical Oncology (2013)

8080 Background: Two double-blind, prospective, randomized, placebo-controlled trials demonstrated survival benefit in unselected populations with advanced NSCLC in the 2nd/3rd line (BR.21) and maintenance setting (SATURN). The efficacy of erlotinib in patients with EGFR WT NSCLC has been questioned. We examined the impact of erlotinib vs placebo in confirmed EGFR WT patients in both studies. Methods: Combined re-analysis of progression-free survival (PFS) (from date of randomization to investigator-assessed progression or death from any cause), and overall survival (OS) (from date of randomization to death from any cause) in patients with known WT EGFR. PFS and OS were estimated by Kaplan-Meier curves and compared by 2-sided log-rank test. Cox proportional hazards model was used to estimate hazard ratios (HR) adjusted for potential confounders. Sensitivity analyses assessed comparability of patients with known and unknown EGFR mutation status to determine generalizability of the two study populations. Results: 74% of the BR.21 population (n=150) and 89% of the SATURN population (n=388) with known EGFR mutation status had WT EGFR. PFS and OS for individual and combined analyses are shown (Table). Adjusting for non-randomized therapy after study therapy discontinuation, HR for OS was 0.74 (0.61–0.91); p&lt;0.01. Baseline characteristics were similar for patients with known and unknown EGFR status, suggesting generalizability of the EGFR WT data. Erlotinib benefit was sustained in all clinical subsets. Conclusions: Erlotinib provided a consistent and significant improvement in survival for patients with EGFR WT NSCLC in both studies, individually and in combination. The benefit of erlotinib does not appear to be limited to patients with activating EGFR mutations. [Table: see text]
Curative treatment in gallbladder cancer: Adjuvant or multimodal concepts—Evidence from data of 975 cases of The German Registry of Incidental Gallbladder Carcinoma.
Authors: Thorsten Oliver Goetze, Salah-Eddin Al-Batran, Vittorio Paolucci
Journal: Journal of Clinical Oncology (2017)

367 Background: Incidental gallbladder cancer (IGBC) in T1b-3 stage do profit from radical cholecystectomy but nevertheless the cure rate in T2-3 carcinomas is disappointing. For improvement, following questions are of interest. What is significant regarding adjuvant or multimodal aspects? Which technique of liver resection (LR) and lymph- node dissection (LAD) is meaningful? Role of lymph node ratio (LNR)? Answers based on the data of 975 IGBC of the GR- platform. Methods: For data analysis we used the German- Registry- platform (GR). The GR is a network of more than 300 clinics in Germany. More than 1000 cases of IGBC are registered and to the knowledge of the authors the largest prospective gallbladder registry worldwide. Results: To date more than 1000 IGBC in the GR have been registered, n = 975 analyzed. In 44 of 119 T1b cases there was an IRR, with a significant survival benefit for T1b after IRR. There was also a significant survival benefit for the 244 T2 and 86 T3 with IRR of the 492 T2 and 228 T3 tumors. Comparison of LR showed good results for the wedge resection technique (WRT) in T1b and T2. For T3 more radical techniques showed better results. In 233 patients the LNR could be calculated. Statistic indicates that LNR has a significant influence on prognosis. The results show that the referral of patients from a LV to a HV has no practical relevance. In n = 433 T2 / T3 patients there are data calculated about adjuvant therapy, with a highly significant survival benefit after adjuvant therapy in T2 and a trend for a survival benefit in T3 carcinomas. Positive effect of adjuvant therapy exists in the subgroup with and without re- resection but was more evident in patients without radical resection. Conclusions: IGBC's up to T1b needs radical surgery. The WRT is attractive for T1b / T2 IGBC. LAD and LNR are of prognostic relevance. In 433 T2-3 IGBC's, adjuvant therapy has a positive effect, especially in cases without radical surgery. Regimen will be discussed at the meeting. For further improvement in T2-3 IGBC a multimodal therapy (GAIN-) trial has already been planned by the investigator of the GR under the support of the GR- platform with more than 300 clinics in Germany.