bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of life (QoL) and content validity in objective tumor response.
Authors: Twelves Christopher , Awada Ahmad , Kaufman Peter Andrew , Yelle Louise , Perez Edith A. , Velikova Galina , Wanders Jantien , Olivo Martin S. , He Yi , Dutcus Corina , Simons W. Robert , Cortes Javier 
Published: March 2020

1055^ Background: Key properties of QoL instruments in a clinical trial setting are reliability, the ability to detect a change, and content validity. Using data from the Study 301 phase III breast cancer trial, we report here content validity and ability to detect a change for the EORTC QLQ-C30 and breast cancer-specific QLQ-BR23 questionnaires. Methods: Patients with locally advanced or metastatic breast cancer were randomized to 21-day cycles of either eribulin mesylate 1.4 mg/m2 given on Days 1 and 8, or capecitabine 1.25 g/m2BID orally on Days 1-14. QoL questionnaires were completed at baseline and at 6 weeks, 3, 6, 12, 18, and 24 months. Objective tumor response was evaluated (complete response [CR]; partial response [PR]; stable disease [SD]; progressive disease [PD]). Univariate and multivariate longitudinal analyses using weighted generalized estimating equations were employed to assess the responsiveness of the QoL scales to objective tumor response. Results: 1,102 patients were randomized (554 eribulin, 548 capecitabine). Global health status (GHS)/QoL scores were low at baseline (55). GHS/QoL scores were highest for patients with CR (70.8), followed by those patients with PR (63.5), SD (60.5), and PD (58.1). Physical functioning followed the same pattern: CR (98.3); PR (79.1); SD (72.8); PD (71.0). Role and social functioning scores were also responsive. Pain increased, while fatigue and body image worsened, with poorer tumor responses. Using the weighted generalized estimating equations, there were improvements in physical (34.78; p<0.01), cognitive (27.29; p<0.01), and social (22.04; p<0.01) functioning, and future perspective 11.47 (p<0.01), in patients who responded (CR and PR) to treatment compared with non-responders. Pain decreased significantly by 28.62 (p<0.01) on a 0-100 scale. Patients who responded also gained appetite and had fewer breast symptoms. Conclusions: These results suggest content validity of the EORTC QLQ-30 and QLQ-BR23 questionnaires as they correlate with changes in objective tumor assessments. Clinical trial information: NCT00337103.
Clinicopathologic predictors (CP) of survival in patients with endometrial stromal sarcomas (ESS) treated with multi-modality therapy.
Authors: Dalia Samir , Conley Anthony Paul , Fisher Kate , Lee Ji-Hyun , Wenham Robert Michael , Apte Sachin , Gonzalez Ricardo Jorge 
Published: March 2020

10556 Background: ESS is a rare uterine neoplasm in which there is minimal data about CP prognostic markers. Our study aims to determine the association of CP variables on overall survival (OS). Methods: Patients at Moffitt Cancer Center between January 1, 1990 and April 30, 2012 with the diagnosis of ESS were identified using our institutional database. Vital status, demographics, and therapeutic information were recorded. Survival time was estimated using the Kaplan-Meier method, and Cox proportional hazard model was used to identify potential risk factors for the time to event data. A p value < 0.05 was significant. Results: 64 patients were identified. 11 were excluded for incomplete records or inaccurate pathology, and 53 patients were analyzed. Median OS was 214 months (95% Confidence Interval (CI) 60-338). Median follow up was 133 months (95% CI 84-182). Mean age was 53±14 years, 45 (85%) underwent oophorectomy at or prior to diagnosis, 12 (23%) were diagnosed with metastatic disease, 37 (70%) were low grade, 19 (36%) were FIGO stage III-IV. Mean BMI was 29±8 kg/m2, 23 (43%) received adjuvant therapy (adjT) of any type (hormonal, chemotherapy, or radiation) and 16 (30%) received hormonal therapy at any time (HRT). 27 (51%) patients had ER or PR testing and 19 (70%) were ER(+), 20 (74%) were PR (+). The sample size was too small for multi-variable analysis. The Table shows the results of select univariable analysis and OS. Conclusions: Age, initial tumor size, ER and PR status had the greatest impact on survival while BMI, FIGO stage, AdjT or HRT did not. The association between survival and ER or PR status was seen independent of if a patient received HRT. Multicenter collaborative efforts are needed in order to further study the effects of ER and PR status on survival in ESS. [Table: see text]
Recombinant adenoviral human p53 gene combined with radiotherapy in treatment-advanced sarcoma.
Authors: Geng Jianhao , Xiao Shaowen , Zhang Shenwen 
Published: March 2020

10557 Background: Advanced soft tissue sarcoma generally are resistant both chemo- and radiotherapy. P53 gene has multiple anti-tumor functions including sensitizing tumor cells to chemo- or radiotherapy. Methods: Thirty-six patients with advanced, unresectable soft tissue sarcoma, with an age of 48.3±19.1 years old, 19 males and 17 females, were treated with combination of p53 gene and radiotherapy. Recombinant adenoviral human p53 gene (rAd-p53) was given through intratumoral injection at a dose of 2 x 1012 rAd-p53 viral particles (VP) once per week for 4-9 times. If tumors spread to the peritoneal cavity with or without malignant peritoneal effusions, 2 x 1012 VP diluted into 500 ml of physiological saline was infused into abdominal cavity, once a week for 4 times. Intensity modulated radiation therapy were given at a total dose of 20 – 70 Gy in 2-7 weeks. Results: The overall response rate at 3 months after treatment was 44.4% (16/36, 2/36 in CR and 14/36 in PR). Twenty patients (55.5%) were stable. The tumor in two patients was successfully resected after the combined therapy. Medium overall survival and progress free survival time were 17.8 and 13.5 months, respectively. The survival rates of one year, two years three years, and 5 years were 58.3%, 25.0%, 13.9%, and 8.3%, respectively. Mild or medium fever was observed in all patients after application of rAd-p53. No serious adverse events or complications observed. Conclusions: Combination of local p53 gene and radio-therapy is effective and safe treatment regimen for advanced soft tissue sarcoma.
Expression of neurotrophins and their receptors in adult sarcomas.
Authors: Malenke Elke , Dorn Christiane , Wirths Stefan , Mueller Martin Rudolf , Kanz Lothar , Kopp Hans-Georg 
Published: March 2020

10562 Background: Neurotrophins (NT) influence proliferation, survival, death, and differentiation by binding Tropomyosin-related kinase (Trk) receptors and p75NTR(CD271). While the three Trk-receptors TrkA, TrkB, and TrkC display specific binding to their ligands, i.e. TrkA to NGF (nerve growth factor), TrkB to BDNF (brain-derived neurotrophic factor), NT4/5 (neurotrophin 4/5) and TrkC to NT3 (neurotrophin 3), CD271 shows low affinity to all neurotrophins. Notably, CD271 has been suggested as marker for the prospective isolation of bone marrow mesenchymal stromal cells (MSC), and rhabdomyosarcomas have previously been found to express neurotrophins and NT receptors. Methods: RNA was isolated from sarcoma cell lines and freshly obtained sarcoma (src) cells from patients after surgical resection. RNA was reverse transcribed and cDNA products underwent PCR analysis with specific primers. Furthermore, cell lines from the same primary tissues were established and treated with doxorubicin. Effects of K252a (Trk receptor inhibitor), Pep5 (CD271-Inhibitor), and neurotrophins on sarcoma cell proliferation and survival were analyzed. Results: An array of freshly obtained clinical src samples (n=10 each subtype) was screened for expression of NT3, NT4/5, BDNF, NGF as well as TrkA, TrkB, TrkC, and CD271. Interestingly, src subtype-specific expression patterns were observed. In the established cell lines, K252a increased doxorubicin-induced tumor cell death, while CD271-Inhibitor Pep5 enhanced proliferation in doxorubicin treated cells, especially under serum free conditions and when combined with BDNF and NGF. Conclusions: NT and NT receptors are expressed on all adult src samples screened in this study. Chemotherapy resistant liposrc as well as myxofibrosrc samples displayed the strongest expression of NT3 as well as TrkB, TrkC, and CD271. The concomitant expression of NT and their receptors suggests autocrine self-stimulation, which may propagate survival, proliferation, and treatment resistance. NT receptor tyrosine kinases may represent an interesting therapeutic target in adult src.
Two doses of NGR-hTNF (N) given alone or in combination with doxorubicin (D) in soft tissue sarcomas (STS).
Authors: Ferrari Stefano , Casali Paolo Giovanni , Blay Jean-Yves , Tonini Giuseppe , Le Cesne Axel , Ali Nasim , Perfetti Vittorio , Palmerini Emanuela , Palassini Elena , Ray-Coquard Isabelle , Vincenzi Bruno , Domont Julien , Marchesi Emanuela , Marrari Andrea , Cassier Philippe Alexandre , Silletta Marianna , Stacchiotti Silvia , Lambiase Antonio , Bordignon Claudio 
Published: March 2020

10568 Background: N, a tumor-targeted antivascular agent, displays a biphasic dose response curve with activity shown at low dose (LD) or high dose (HD). Vascular effects involve at LD an early vessel stabilization that enhances intratumor D uptake followed by late vessel damage and at HD a rapid vessel disruption. Methods: STS patients (pts), stratified by prior D dose (> vs ≤ 300 mg/m2), were randomized to N alone given at LD (0.8 μg/m2) in arm A and at HD (45 μg/m2/d1/q1w) in B, or combined with D (60 mg/m2/d1/q3w/6 cycles) at LD in arm C and at HD in D. Primary aim of this 4-arm phase II trial was progression free survival (PFS) with CT scans performed q6w until progressive disease (PD). Using 2-stage design, each regimen was rejected if ≤ 2/14 and ≤ 7/24 pts were PD free at 3 months after 1st and 2nd stage, respectively (β=20%, α=10%, n=96). Secondary aims: adverse events (AEs), response rate by RECIST criteria and early metabolic response (MR), as quantified by fractional change in SUV using FDG-PET according to EORTC criteria Results: 66 pts have been enrolled and 55 were included in 1st study stage analysis: median age: 57 yrs; male: 30; PS ≥ 1: 26; leiomyosarcomas: 12; median prior lines: 3 (range, 0-7). In all, 488 weekly cycles were given (mean, 9; range, 1-45). Main grade 3/4 AEs were: neutropenia 18%, chills 7%. After first study stage, primary endpoint was met only in arm C (LD N + D), with 7/14 pts PD free at 3 months. Median PFS was 1.3 months (95% CI, 1.1-1.5) for arm A, 1.5 (1.1-1.8) for B, 4.5 (3.6-5.4) for C and 1.3 (1.1-1.5) for D (p=.01 for trend). By RECIST, there were no objective responses and 20/48 (42%) evaluable pts had stable disease (SD), including 1/12 in arm A, 6/12 in B, 9/12 in C and 4/12 in D. Median SD duration in arm C was 5.5 months (95% CI, 3.7-7.3). By FDG-PET imaging done after 3 weeks, 7/30 (23%) assessable pts had partial MR (4 SD/3 PD per RECIST), with mean change in SUV of -34% (SD, ± 12), while 18 pts (60%) had stable MR (7 SD/11 PD per RECIST), with mean change in SUV of 2% (± 11). Median PFS was 4.2 months in pts who achieved partial MR and 1.5 months in pts who did not (HR=0.67). Complete follow-up for arm C and central histology/radiology review are under way. Conclusions: LD NGR-hTNF plus D is safe, with promising activity as measured by FDG-PET. Clinical trial information: NCT00484341.
Epithelioid haemangioendothelioma.
Authors: Yousaf Nadia , Benson Charlotte , Al-muderis Omar , Fisher Cyril , Judson Ian Robert 
Published: March 2020

10569 Background: Epithelioid haemangioendothelioma (EHE) is a rare vascular tumour which can arise in any site. There is little published data about the clinical behaviour and management of these tumours. Methods: A retrospective review of the management of patients with histologically proven EHE presenting to the Royal Marsden Hospital from January 1999 to January 2012. Demographics, site, treatment and survival outcomes were collected. Results: 28 patients (21 females) were identified with a mean (SD) age of 44 (17). 20 patients presented with diffuse disease involving one or more organs at presentation. The predominant site of disease was identified as liver n=8, mediastinum n=6, lung n= 2, limb n=1, pancreas n=1, spleen n=1, back n=1, abdominal wall n=1, oesophagus n=1, neck n=1, pelvis n=1, not known n=2. Median overall survival (Interquartile range) [OS (IQR)] in months was the longest in 10 patients who had localised operable disease at presentation, 116 (71). Amongst those with inoperable disease (n=16), patients with liver disease had the longest OS (IQR), 18 (43) months and those with lung and mediastinal disease had the shortest OS (IQR), 10 (2.5) and 11 (17) months respectively. A variety of treatment modalities were used for patients with inoperable disease and these are summarised in the Table. Conclusions: The clinical behaviour of EHE can vary depending on the site of disease. Surgery, if feasible, has the best outcome. In those with inoperable disease a period of observation to assess the clinical behaviour of the tumour is recommended. Non-steroidal anti-inflammatory drugs are a reasonable, relatively non-toxic first line treatment option. The use of anti-angiogenic drugs merits further exploration. [Table: see text]
Identification of potential molecular biomarkers for response of soft tissue sarcoma to eribulin: Translational results of EORTC trial 62052.
Authors: Wozniak Agnieszka , Wiemer Erik A.C. , Burger Herman , Allemeersch Joke , van Eijsden Rudy , Mathijssen Ron H.J. , Sleijfer Stefan , Smid Marcel , Floris Giuseppe , Marreaud Sandrine , Nzokirantevye Axelle , Sciot Raf , Schoffski Patrick 
Published: March 2020

10573 Background: The phase II study EORTC 62052 demonstrated potential antitumor activity of eribulin, a tubulin-interacting cytotoxic agent, which is a synthetic analogue of the natural compound halichondrin B, in patients with various subtypes of metastatic soft tissue sarcoma (STS) including leiomyo- (LMS) and adipocytic (ADI) sarcomas, but not synovial sarcomas (SYN) and other sarcoma histotypes (OTH) (Schöffski P et al. Lancet Oncol. 2011;12:1045). In addition to histotypes, we aimed to identify potential biomarkers responsible for eribulin sensitivity or resistance to eribulin using gene expression and miRNA profiling. Methods: From 68 consenting patients archived tumor tissue was collected, including 22 LMS, 15 ADI, 10 SYN and 21 OTH sarcoma histotypes. Total RNA was isolated from 65 samples and analyzed using GeneChip Human Exon ST Array (for mRNA expression) and Taqman Low Density Array (for miRNA). Progression free survival (PFS) at week 12 (RECIST 1.0) was the primary endpoint of the clinical trial and used for correlative studies. Eighteen out of 56 (32.1%) evaluable patients in this analyzed subset had non progressive disease at week 12 (“responders”). Results: Overall expression of 62 transcripts including ALS2CR11 (uncorrected p<0.001) and 26 miRNAs (p<0.05) differed significantly between non-responders and responders. Additional transcripts and miRNAs were identified when considering the different histological groups (Table). Conclusions: The level of (mi)RNA expression in soft tissue sarcoma samples may predict response of soft tissue sarcoma to eribulin. Further validation studies are required. [Table: see text]
Incidence and predictive factors of late relapse in patients with soft tissue sarcomas: Implications for prolonged follow-up.
Authors: Toulmonde Maud , Le Cesne Axel , Mendiboure Jean , Blay Jean-Yves , Piperno-Neumann Sophie , Chevreau Christine , Delcambre Corinne , Penel Nicolas , Terrier Philippe , Ranchere-Vince Dominique , Lae Marick , Le Guellec Sophie , Michels Jean-Jacques , Robin Yves Marie , Italiano Antoine 
Published: March 2020

10574 Background: There is no consensus on how to follow soft-tissue sarcoma (STS) patients after their initial management. In particular, the incidence of late relapse which would justify prolonged surveillance is unknown. Methods: Follow-up data were reviewed from 719 patients with localized STS, included in the French Sarcoma Group database from January 1990 to June 2005, and who achieved complete remission maintained for at least five years after their initial management. The outcomes of interest were the cumulative probabilities of late (> 5 years) local and metastatic relapse with death as a competing event. Estimations and 95% confidence intervals (CIs) were computed with the cumulative incidence function. Patients who did not experience the event of interest or death over the course of the study were censored at their last follow-up. Results: 67 (9.3%) and 42 (5.8%) patients had late local and metastatic relapse respectively. On univariate analysis, internal trunk location, liposarcoma histological subtype, tumor size > 10 cm, R1 margins, no adjuvant radiotherapy were significantly associated with increased risk of late local relapse. On multivariate analysis, internal trunk location (HR= 3.9, 95% CI 2.2-6.7, p<0.001) and tumor size > 10 cm (HR= 2.1, 95% CI 1.1-4, p=0.03) were the two factors independently associated with local relapse. On univariate analysis, leiomyosarcoma histological subtype, and grade > 1 were significantly associated with increased risk of late metastatic relapse. On multivariate analysis, grade > 1 (HR= 4.7, 95% CI 1.1-21, p=0.04) was the sole factor independently associated with the risk of late metastatic relapse. Conclusions: Late relapse of STS (> 5 years after initial management) is relatively uncommon. However, its existence and our results emphasize the critical role of long-term follow-up to detect late local recurrence in patients with retroperitoneal or very large STS and late metastatic recurrence in patients with high grade disease.
Safety of trabectedin (T) in elderly patients (pts) with advanced soft tissue sarcoma (STS).
Authors: Sanfilippo Roberta , Baldi Giacomo Giulio , Fumagalli Elena , Marrari Andrea , Bertulli Rossella , Palassini Elena , Stacchiotti Silvia , Libertini Michela , Casali Paolo Giovanni 
Published: March 2020

10576 Background: T is a marine-derived cytoxic alkaloid approved in the European Union for further-line chemotherapy of advanced STS. Most common side effects are fatigue, neutropenia and transient transaminitis. Overall the drug is well tolerated with no cumulative toxicity. Studies in elderly pts are lacking. Methods: We retrospectively reviewed all pts ≥65 year-old, with pre-treated advanced STS, who received T at our Institution from January 2002 to January 2013, focusing on tolerability. All patients received premedication with dexamethasone 4 mg p.o. bid 24 hours prior to T administration. Treatment toxicity was graded according to CTCAE (v 4.0). Results: Fourty-two pts were identified (males = 22, females = 20; median age = 69 years, range 65-82; ECOG PS 0 = 1 pt, 1= 38 pts and 2-3= 3 pts; main histotypes = 22 liposarcoma: 12 myxoid-round cell liposarcoma, 10 well/dedifferentiated liposarcoma, 17 leiomyosarcoma, 2 synovial sarcoma, 4 others; disease extent = 34 metastatic and 8 locally advanced; median line of administration of T= 3rd, range 1st-5th; median T dose = 2.2 mg, range = 2.7-1.7 mg). A total of 319 cycles were administered (median 6, range = 1-23). Starting dose was 1.3 mg/mq in 37 pts and 1.1 mg in 5 pts. The most common side effects were: fatigue (all grades: 19% of cycles), reversible myelosuppression, mainly neutropenia (grade 3-4: 50%), transient transaminitis (grade 3-4: 21%). Eighteen pts needed a dose reduction: inter-cycle transient transaminitis (3 pts), neutropenia ( 13 pts), asthenia (2 pts). In 7 patients, cycles needed to be delayed as well. Three pts interrupted T due to toxicity: grade 3 thrombocytopenia in 1 pt and grade 4 neutropenia in 2 pts. Conclusions: This retrospective analysis confirms that T is well tolerated in elderly pts. No major differences were found in the safety profile compared to historical controls, except a higher incidence of myelosuppression, which however was not influential on subsequent T administration.
Targeted radiofrequency ablation of metastatic posterior vertebral body lesions in patients with soft tissue sarcomas.
Authors: Ley Jessica C. , Jennings Jack , Baker Jonathan C , Hillen Travis , Van Tine Brian Andrew 
Published: March 2020

10585 Background: Metastatic spinal lesions can be debilitating with significant impact on patients quality of life. Concern for damage to adjacent neural elements during treatment exist due to high radiation doses required to treat certain radioresistant spinal lesions such as soft tissue sarcoma. Radiofrequency ablation (RFA) of metastatic lesions has been shown to be effective in bone. Spine anatomy presents challenges for minimally invasive (MI) treatment of posterior vertebral body lesions. Targeted RFA (t-RFA) using a novel tumor ablation system, designed for spinal anatomy is evaluated in patients with symptomatic posterior vertebral wall spinal lesions. Methods: Five patients with metastatic leiomyosarcoma or liposarcoma and posterior vertebral body spine lesions, treated by prior radiation with continued progression of lesion size and pain received t-RFA, using a novel spinal tumor ablation system (STAR, DFINE), which contains an articulating bipolar, extensible electrode for navigation. Device thermocouples (TC) permit real time monitoring of the ablation zones to determine size. Sequential post-procedural pain scores, PET and contrast enhanced magnetic resonance imaging, and histopathology of treated area was performed. Results: No complications or thermal injury occurred. Intra-procedural imaging demonstrated the articulated, bipolar instrument was able to navigate to posterior lesions. Post-ablation MRI demonstrated lesion necrosis within a discrete ablation zone. No evidence of malignancy by PET or histopathology was noted through 10 months. All patients reported post procedural pain relief. Systemic therapy was not interrupted. Conclusions: Navigational t-RFA proved a safe and effective, non-ionizing palliative therapy alternative for radio-resistant lesions . Post-ablation imaging and histology confirmed metastatic lesions were necrotic and included in ablation zone with tumor control 10 mos post treatment. Ablation zone was very consistent with real time temperature readings. t-RFA permitted MI targeted treatment of lesions within close proximity of spinal cord, not controlled by systemic therapy. Prospective clinical trial is under preparation.