bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of infusion duration on high-dose methotrexate (HDMTX) acute kidney injury (AKI).
Authors: Fox Elizabeth , Busch Christine , DeBernardo Alexander , Levin Kristin , Zhu Yan , Bagatell Rochelle , Balamuth Naomi Jill , Womer Richard B. , Balis Frank M. ,   Children's Hospital of Philadelphia Bone and Soft Tissue Tumor Program
Published: September 2018

e22013 Background: HDMTX AKI delays MTX excretion and increases the risk for severe systemic toxicity. MTX is thought to crystalize in renal tubules at urine [MTX] above the solubility limit, leading to AKI. Methods: Pharmacokinetic simulations of plasma and urine [MTX] at varying infusion durations (IDs) for 12 g/m2 MTX dose identified 12 h as the shortest duration with urine [MTX] below the solubility limit at pH 7.5. Using a randomized crossover design, we compared 4h and 12h IDs in patients with osteosarcoma treated with 12 g/m2 MTX. Urine AKI biomarkers (NAG, NGAL, KIM-1), urinalysis, and estimated glomerular filtration rate (GFR) were endpoints. [MTX] was measured in plasma using a commercial fluorescence polarization assay and in urine by HPLC. Results: Twelve patients, age 12.8 (5.6-19) y, received 12 g/m2 HDMTX over 4 h (40 infusions) and 12 h (35 infusions). At baseline (BL), GFR was 120 (100-175) mL/min/1.73m2; Median (range) NAG [21(5-64) U/gCr] and NGAL [11(0.7-325) µg/gCr] were normal and KIM-1 [0.9(0.4-6.3) µg/gCr] was elevated. Urine pH was maintained > 7 for all infusions. Proteinuria occurred during 93% of infusions. Table 1 compares 4h and 12h IDs. One patient had HDMTX AKI during a 12 h ID (data excluded from Table); end of infusion (EOI) [MTX] was 930 µM in plasma and 38 mM in urine. By 24h after the start of the HDMTX infusion, serum creatinine (sCr) was 1.4 mg/dL (3.5x BL), cystatin C was 1.0 (1.4x BL); NAG, NGAL and Kim-1 increased by > 350%. At 40h, plasma [MTX] was 40 µM; glucarpidase was administered. Plasma [MTX] < 0.1 µM was achieved at 310 h. Recovery to BL occurred at 20 d for sCr and 40 d for cystatin C. Conclusions: Transient proteinuria, increase in KIM-1 and NAG indicate acute proximal renal tubular damage in all HDMTX infusions regardless of ID. EOI urine [MTX] after 4 h or 12 h IDs did not exceed the solubility limit, including the patient with clinical HDMTX AKI. These results suggest that MTX crystallization in urine may not be the primary mechanism of HDMTX AKI. Clinical trial information: NCT01848457. [Table: see text]
A preliminary study of apatinib in Chinese patients with osteosarcoma.
Authors: Zhou Yong , Tang Fan , Min Li , Zhang Wenli , Shi Rui , Luo Yi , Duan Hong , Tu Chongqi 
Published: September 2018

e22500 Background: Osteosarcoma is the most common malignant tumor of bone that displays hyperproliferative characteristics and high vascularity, making vascular endothelial growth factor receptors (VEGFRs) become promising targets. Apatinib, a tyrosine kinase inhibitor targeting VEGFR-2, shows anti-cancer effects against a broad range of malignancies. This study reported the clinical experience of apatinib in osteosarcoma. Methods: We collected the medical data of osteosarcoma cases who received apatinib for at least one month in our hospital. The objective response rate (ORR), disease control rate (DCR), and 6-month progression-free survival (PFS) and overall survival (OS) rates were evaluated, and the safety profile was observed. The cut-off date of analysis was 01/17/2017. Results: Between May 2015 and Nov 2016, a total of 34 cases received apatinib with informed consent (4 as neoadjuvant, 1 as neoadjuvant and first line, 10 as first line, 15 as second line and 4 as third line). Among them, 18 (52.9%) cases suffered from pulmonary metastases before apatinib administration; 29 (85.3%) patients had an Eastern Cooperative Oncology Group performance status of 1–2. Initial dosages of 250, 425, and 500 mg/d were given to 5 (14.7%), 3 (8.8%), and 26 (76.5%) cases, respectively. Dosage adjustment occurred in only 8 (23.5%) patients. The median duration was 5.9 months (95%CI, 4.5–9.4 months). According to RECIST v1.1, complete response, partial response, stable disease and progressive disease were achieved in 1 (2.9%), 6 (17.6%), 25 (73.5%) and 2 (5.9%) patients, respectively. The ORR was 20.5%, and the DCR was 94.1%. Patients with pulmonary metastases showed a relatively better response to apatinib, as the ORR and DCR were 33.3% and 88.9%, respectively. As for safety analysis, the most 3 common adverse events (AEs) were hand-foot syndrome (HFS) (29, 85.3%), diarrhea (16, 47.1%), and decreased appetite (9, 26.5%). Nine grade III AEs were occurred including 3 HFS, 2 hypertension, 1 diarrhea, 1 oral mucositis, 1 proteinuria and 1 serious peeling. Conclusions: Apatinib seems to be effective in treating osteosarcoma with acceptable safety profile. Perspective clinical studies with adequate sample size are required to validate our results.
Pre-operative tomotherapy for retroperitoneal liposarcoma: Results of a phase II multicenter study.
Authors: Kantor Guy , Stoeckle Eberhard , Delannes Martine , Mahe Marc-Andre , Italiano Antoine , Kind Michèle , Dupouy Christine , Giraud Antoine , Antoine Mikael , Toulmonde Maud , Mervoyer Augustin , Ferron Gwennael , Bellera Carine A. , Sargos Paul 
Published: September 2018

e22501 Background: To evaluate efficacy and feasibility of radiotherapy (RT: high-level dose 54 Gy, with 30 fractions over / 6 weeks) followed by surgery, for retroperitoneal liposarcomas. Methods: Helical tomotherapy was used for pre-operative RT. Clinical Target Volume (CTV) and main organs at risk were systematically delineated with the surgeon. Surgery was planned 4 to 8 weeks after RT. Inclusion criteria were operable, biopsy-proven, retroperitoneal liposarcomas. Toxicity was graded according to CTCAE V3.0. Overall survival (OS) was estimated using Kaplan-Meier method. Due to competing risks, we estimated the cumulative incidence of loco-regional relapse; 95% confidence intervals are reported [95%CI]. Results: Patients:From 04/2009 to 09/2013, 48 patients were included. Mean age: 62 years (y) (36 to 82). All but 1 patient were OMS ≤ 2. Histological types were 20 well differentiated (WDLS) and 28 dedifferentiated liposarcomas. Mean CTV was 2954 cc. Treatment:1 patient did not have surgery. Dosimetric constraints were respected. Monobloc exerese was systematically achieved. Surgical margins were R0 (16; 34%), R1 (28; 60%), R2 (2; 4%) or missing (1; 2%). Oncological outcomes:Median follow-up was 4.7 y. Cumulative incidence of loco-regional relapse at 3 and 5 y was 17% [8%; 29%] and 31% [16%; 47%] respectively. Estimates were 5% and 35% for dedifferentiated liposarcoma and 26% and 26% for well differentiated liposarcoma. OS at 3 and 5 y was 81% [66%; 89%]) and 78% ([63%; 88%] respectively. Toxicity: 2 months after surgery, 10 grade 3 toxicities and 1 grade 4 toxicity were reported for 6 patients; 3 patients died within 6 months after surgery, 2 of which were related to treatment. After 1 y, no further severe toxicity was observed; 5 cases of second cancers were reported: 1 myeloid leukeamia, 2 pancreatic, 2 breast carcinomas. Conclusions: This trial highlights the feasibility of preoperative 54 Gy RT. Although efficacy data (local control and OS) are encouraging, high incidence rates of acute toxicities and second cancers should be considered. Preoperative RT for WDLS remains questionable. Results from ongoing EORTC phase III Strass trial may provide further level of evidence for this approach. Clinical trial information: NCT01841047.
Response of advanced soft tissue sarcoma to apatinib: A retrospective analysis.
Authors: Yang Wuwei , Zhu Baorang , Li Jing , Xie Qiaosheng , Diao Liyan , Gai Lvhua 
Published: September 2018

e22502 Background: Soft tissue sarcomas (STSs) are rare but malignant tumors with high risks of local recurrence and distant metastasis. Promising efficacy of apatinib was reported in several subtypes of STSs (Dong et al. 2016, Medicine 95: e4368; Ji et al. 2016, OncoTargets and therapy 9:643-647). We aimed to preliminarily assess the short efficacy and safety of apatinib, an oral tyrosine kinase inhibitor targeting VEFGR-2, in patients with advanced STS. Methods: The medical records of 31 patients who received apatinib between September 2015 and August 2016 were retrospectively reviewed to evaluate the short efficacy, time to progression (TTP) and safety. Results: Nineteen (61.3%) patients taken apatinib after failing second or even more lines of cytotoxic chemotherapy, 8 (25.8%) patients received apatinib as second-line therapy, and 4 (12.9%) cases who refused chemotherapy was given apatinib as first-line therapy. In the study cohort, one patient was treated with apatinib as adjunctive therapy after ablation, while the remaining 30 as salvage therapy. Administration was stopped in 6 cases due to adverse events (n = 3) or personal reasons (n = 3). As a result, 24 patients were eligible for tumor response to apatinib evaluation, and 25 patients were available for survival analysis. The objective response rate was 33.3% and clinical benefit rate was as high as 75.0%. The median TTP was 4.3 months (range, 1.8–11.6 months). Most of the AEs were at grade 1 or 2. The grade 3 AEs were hypertension (n = 2, 6.5%), hand-foot syndrome (n = 2, 6.5%), and diarrhea (n = 1, 3.2%). No grade 4 AE or drug-related mortality occurred. Conclusions: Apatinib showed promising efficacy and acceptable safety profile in metastatic or recurrent STS, giving rationale clinical evidence to conduct clinical trials.
A nonrandom association of sarcoidosis in patients with gastrointestinal stromal tumor and other sarcomas.
Authors: Espejo Freire Andrea Patricia , Ramdial Jeremy , Wilky Breelyn A. , Kerr Darcy , Trent Jonathan C. 
Published: September 2018

e22521 Background: Sarcoidosis can mimic metastatic cancer. Although sarcoidosis is associated with carcinomas, there are limited data supporting its association with GIST and other sarcomas. Prior reports on cancer related sarcoidosis are inconsistent in terms of prognosis; while some reports link sarcoidosis with a favorable prognosis, others associate it with recurrence and secondary malignancies. Here we describe a series of 7 patients with diagnosis of sarcoma and sarcoidosis seen at a single sarcoma center in South Florida. Methods: Seven patients with diagnosis of both sarcoma and sarcoidosis were identified over the period of 2007 to 2016. Data of presentation, treatment, histology and outcome was tabulated for analysis. The Standardized Incidence Ratio (SIR) was calculated for the state of Florida and for our hospital catchment area. Results: Of the seven patients, 4 cases were GIST, 1 case of unclassified spindled and epithelioid cell sarcoma that coexisted with tenosynovial giant cell tumor, 1 case of uterine leiomyosarcoma, and 1 case of myxofibrosarcoma. Sarcoidosis was diagnosed before sarcoma in 3 patients, after the diagnosis of sarcoma in 3 patients and at the same time of sarcoma diagnosis in 1 patient. All cases of sarcoidosis involved the lungs. From our series, 3 patients have shown no progression of sarcoma, 1 is alive with sarcoma, 2 died due to progression of sarcoma and 1 was lost to follow up. Statistical analyses showed a SIR = 268 (95% CI 106-503), when comparing to the expected incidence in the state of Florida and SIR = 831 (95% CI 329-1562), when comparing to the expected incidence in our catchment area. Conclusions: This case series points to a statistically robust, non-random, association between Sarcoma and Sarcoidosis that has not been previously described. Our study found the lung is not only the most common site of sarcoma metastasis but also the most common site of sarcoidosis. These results infer that patients with presumed metastatic sarcoma should be considered for a biopsy to rule out a benign process such as sarcoidosis. Additionally, the presence of sarcoidosis could be associated with risk of sarcoma. The mechanism of sarcoidosis-associated sarcoma is ongoing.
Metastatic soft tissue sarcomas (STS) in elderly patients: 18 years of monoinstitutional experience.
Authors: Comandone Alessandro , Boglione Antonella , Giubellino Elena , Bergnolo Paola , chiadò Cutin Simona , Dal Canton Orietta , Garetto Ferdinando , Ottaviani Davide , Piana Raimondo , Pochettino Paolo , Prati Veronica 
Published: September 2018

e22528 Background: Elderly people represent more than 50% of STS patients, but few data are available in this population and old patients in clinical studies are underrepresented or not included. Aim of this retrospective, monoinstitutional study is to describe the activity and feasibility of first and second line chemotherapy in elderly patients with metastatic STS. Methods: Patients older than 65, with metastatic STS of the scalp, trunk, girdles and extremities, treated and followed from February 1998 to December 2015 in an Italian referral Center for diagnosis and care of STS were included. Median Overall survival (OS) was the principal end point calculated from the start of chemotherapy to the last date of follow up or death. Response rate and toxicities related to type of administered chemotherapy were the secondary end points. Results: 134 patients (79 M, 55F) were considered, (65-70 y) 63%, (71- 75y) 25%, ( > 76 y)11% . STS histologies: mixoid and round cell liposarcomas (34%), leiomyosarcomas (25%), pleomorphic undifferentiated sarcomas (13%), Angiosarcoma (10%), Mixofibrosarcoma (6%), MPNST (4%), synovial sarcoma (2%), other histologies (6%). All the patients received at least one course chemotherapy (1-12). Mono CT was the preferred administered schedule (92%of cases). Median OS was 7.3 months; at the time of this analysis only 14 patients were alive (10%). In the first line therapy we recorded 1 CR, 14 PR and 43 SD. In second line therapy no CR, 4 PR, 23 SD. PR were recorded mainly in 65-70y old patients. Bad PS, low score in Comprehensive Geriatric Assesment (CGA), vulnerability, comorbidities, number of metastasis, were negative prognostic factors. No toxic death were recorded. 12% of the pts were recovered for febrile neutropenia, thrombocitopenia and mucositis . Conclusions: Our study confirms that elderly patients with metastatic STS is a difficult population to be treated. Only patients less aged, good PS, good GCA and 0-1 comorbidities can be treated with full dose of drug, generally with mono CT. Chemotherapy in elderly pts doesn’t produce a significant improvement in Median Survival and benefit observed support the routine use of citotoxic treatment in selected good performance status population.
Peritoneal metastatic desmoplastic small round cell tumor: A single institution experience.
Authors: Souza Juliana , Mendes Gelcio L. Q. 
Published: September 2018

e22541 Background: Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive tumor that usually occurs in young males. The treatment remains a challenge and despite multiple strategies the tumor leads to death in most cases. Methods: Patients with peritoneal and metastatic DSRCT treated at or referred to National Cancer Institute of Brazil with histological documented diagnosis between July 1997 and September 2014 were identified and their medical records were analyzed. Results: There were 17 patients, the median age of diagnosis was 14.8 years (range: 4-49), with male-female ratio of 3.25. The most common sites of metastasis were liver (n: 7; 53.8%), lung (n: 6; 35%) and both (n: 2; 11.7%). Eight patients (47%) received radiotherapy and 15 patients (88.2%) received chemotherapy, 13 received vincristine, cyclophosphamide, doxorubicin and regimen with or without ifosfamide and etoposide. The median number of cycles received was 12.9 (range:1-27). Three patients (17.6%) who underwent to surgery, received the three treatments. Two patients received only palliative care. After median follow-up of 74 months, 13 patients (76.4%) died, nine patients during the first 2 years. The median overall survival was 16 months. One 6-year old patient was alive after 74 months, after chemotherapy, radiotherapy and surgery. Conclusions: The DSCRT is a rare disease with poor prognosis and high morbidity, that demand an aggressive approach. However, most patients are diagnosed with advanced disease, receiving noncurative approach.
Retroperitoneal lipo-leiomyomata in a woman with history of breast cancer and antiestrogen therapy.
Authors: Moon Jung Joo , Mais Daniel D 
Published: September 2018

e22542 Background: Retroperitoneal lipo-leiomyomata are extremely rare. The usual-type retroperitoneal leiomyoma is itself a rare tumor that is mistaken preoperatively for malignant retroperitoneal tumors or thought of as an exophytic subserosal leiomyoma of the uterus. Lipo-leiomyoma is a variant of leiomyoma with an incidence in uterus ranging between 0.03% - 0.2%, but its presentation as a retroperitoneal mass has not been documented in literature yet. We present a unique case of retroperitoneal lipo-leiomyoma that presented as a diagnostic challenge due to its unique location and unusual histologic appearance. Methods: A 68-year-old female patient with a history of breast cancer diagnosed 4 years ago, currently on antiestrogen therapy (Fulvestrant) and Herceptin, presented to our university hospital with symptomatic left pelvic mass. An abdominal CT showed a heterogeneous low-density pelvic mass with foci of internal calcification and fat with surrounding intermixed intermediate and high density fluid in the expected location of the uterus. Results: A debulking surgery including radical hysterectomy was planned. Intraoperatively, a normal sized uterus was found, the myometrium of which contained multiple variable-sized intramural leiomyomata. In addition, a huge left retroperitoneal mass was found that had no connection to the uterus. Histopathological examination revealed abenign lipoleiomyomatous tumor, composed of an encapsulated proliferation of benign adipocytes and myoid cells intimately admixed. Immunohistochemistry confirmed myoid differentiation, with negative reactions for HMB45 and CKIT, and . MDM2 gene amplification by fluorescence in situ hybridization (FISH) was negative. Conclusions: Some unusually located extra-uterine leiomyomata have been reported; retroperitoneal leiomyoma being among them. Such a tumor with the added feature of lipomatous differentiation presents a differential diagnosis that includes leiomyosarcoma, liposarcoma, angiomyolipoma, and gastrointestinal stromal tumor. The association of an uncommonly located leiomyoma with subsequent lipomatous change withantiestrogen therapy is an unexplored issue that merits further investigation.
Effect of an anti-MARCKS peptide (BIO-11006) on metastasis of lung cancer in vivo.
Authors: Adler Kenneth B , Parikh Indu , Crews Anne , Fang Shijing , Yin Qi , Dickson Brian 
Published: September 2018

e23017 Background: We have previously reported that administration of peptides that inhibit the function of MARCKS (myristoylated alanine-rich C Kinase Substrate) inhibit metastasis of human lung cancer cells orthotopically-injected into the left lung of SCID mice (Chen et al: Oncogene 33:3696–3706, 2014; Chen et al: Am J Resp Crit Care Med 190:1127-1138, 2015). Methods: Here, we administered an anti-MARCKS peptide, BIO-11006, as an inhaled aerosol in 2 models of lung cancer in SCID mice: PC-9 cells orthotopically injected into the left lung, and A549 cells injected into the tail vein. In the orthotopic model, initiation of treatment with BIO-11006 at day 4 post injection of cells and treatment every day thereafter for 4 weeks resulted in dramatic attenuation of tumor metastasis into the lung, heart and diaphragm, with similar attenuation whether the peptides were administered IP or via inhaled aerosol. In additional studies with this model, we waited until day 26 post orthotopic cell injection, a time when there was already extensive metastasis to the lung and distal organs, to begin daily treatment with BIO-11006 via inhalation. Results: There was complete inhibition of further metastasis and primary tumor growth when the animals were examined at day 38 post orthotopic injection of cells. Similar results with the tail vein model were observed: when the peptide was administered by aerosol starting at day 3 post tail vein inoculation, metastasis observed 8 weeks later in distal organs was inhibited by ~ 95% by treatment with inhaled BIO-11006. When PC-9 cells were examined via confocal microscopy, BIO-11006 was seen to cause a cytoskeletal rearrangement so that the cells took on a morphology favoring adherence to the substrate rather than movement. Conclusions: The results suggest that inhaled BIO-11006, already completed in phase 2 clinical trials in patients with COPD, appears to have potent antimetastatic effects in two different mouse models of lung cancer. Clinical trials of inhaled BIO-11006 in patients with advanced lung cancer were initiated in January of 2017.
Sensitivity of TargetSelector in clinical experience in ctDNA profiling of NSCLC 2000 cases.
Authors: Singh Veena M. , Daher Anthony J. , Chen Jeffery J. , Arnold Lyle , Vibat Cecile Rose T. 
Published: September 2018

e23033 Background: Targeted cancer therapy relies on identifying specific DNA mutations from a patient’s tumor. Tyrosine kinase inhibitors (TKIs) tend to be effective for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutations, of which exon 19 deletions (Del19) and L858R are most common. Acquired resistance to TKI therapy is associated with a T790M mutation. Standard biomarker analyses may not reflect tumor heterogeneity; they entail tissue biopsies often with surgical complications. To address these limitations, Biocept developed a minimally invasive method to characterize cancer biomarkers in blood. Biocept's proprietary TargetSelector assays selectively amplify relevant mutations from circulating tumor DNA (ctDNA). Clinical validations demonstrated high concordances between molecular tests in blood vs tissue. As further validation, EGFR mutation detection frequencies were compared to US averages (mycancergenome.org). Here we analyze 2000 blood samples received at Biocept from 1Mar 2016 to 4Jan 2017 from late stage NSCLC patients. Methods: Blood was collected in Biocept OncoCEE BCT validated to preserve DNA ≤ 8 days. TargetSelector was used to detect ctDNA L858R, Del19 and T790M.EGFR allele copy numbers for wild type and each mutant were calculated. The prevalence of each mutation was compared to US averages. Results: Del19, L858R, and T790M mutations were detected in 12.9%, 8.5%, and 9.9% of the analyzed blood samples, respectively. This is concordant with US averages, which are 10% for each mutation. Median copy numbers/ml of blood were 30 for Del19 (range: 1 – 91974), 15 for L858R (range: 1 – 91200), and 10 for T790M (range: 1 – 137360). The median wild type EGFR copy number detected/ml blood was 2304 (range: 8 – 2498725). In ~80% of T790M cases, ≥ 1 concomitant activating mutation was detected. Conclusions: Biocept's TargetSelector detects EGFR mutations (Del19, L585R, and T790M) at a very high level of sensitivity down to 1 mutant copy/ml in advanced NSCLC patients at frequencies consistent with cited US rates. Moreover, the underlying activating mutation was detected in ~80% of T790M cases.