bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trabectedin in pretreated pediatric patients with relapsed or progressive advanced sarcomas: Toxicity and efficacy.
Authors: Palomo Colli Miguel Angel , Medina Sanson Aurora , Lezama -Valle Pablo , Sadowinski Pine Stanislaw , Pérez Villanueva Heynar 
Published: March 2020

e20005 Background: Patients with advanced or metastatic soft tissue and bone sarcomas whose disease progresses after standard chemotherapy (CT) have few options and limited life expectancy. Trabectedin, an alkaloid derived from the sea squirt Ecteinascidia turbinate, has proven activity against some soft tissue (STS) and bone sarcomas. In pediatric patients there is limited information about its efficacy and toxicity profile. Purpose: To describe the toxicity and efficacy of trabectedin in a group of relapsed/refractory pediatric sarcomas. Methods: From January 2009 to December 2011, four relapsed/refractory pediatric sarcoma patients were treated with trabectedin in the Hospital Infantil de Mexico Federico Gomez. Trabectedin was administered as a 24-hour IV infusion every 21 days. Dose levels were 1.3-1.5 mg/m2. All received dexamethasone premedication. Grade 3-4 toxicity was evaluated according to the NCI criteria. Results: Diagnoses included a metastatic Ewing sarcoma, a triton tumor (TT), a metastatic alveolar soft tissue sarcoma and a phylodes sarcoma. All had previously failed to 2 or 3 CT regimens. In 3 patients radiotherapy had also been used and multiple surgical procedures were performed to treat recurrences, before trabectedin. A total of 13 courses of trabectedin were administered. Nausea/vomiting and fatigue were seen in 61.5% of the courses. Laboratory abnormalities included anemia (30.6%), neutropenia (15.3%), ALT (15.3%), AST (15.3%) and GGT (7.7%) elevations and lipasemia/amilasemia (7.7%). One patient presented significant transaminasemia, pancreatitis (probably steroid-related) and died after the first course due to IDC. The TT case, who had a massive unresectable lesion, exhibited a significant response, although her tumor progressed after 4 cycles and eventually died; none of the other patients responded to trabectedin. Conclusions: Trabectedin was generally well tolerated; however we faced a fatal event that might be not trabectedin related. The response observed in the TT case is an interesting finding considering the poor CT response of this aggressive tumor.
Long-term complications after staging laparotomy for Hodgkin lymphoma.
Authors: Rymeski Beth A , Burns Karen Cristly , Nagarajan Rajaram , Correll Judy , Kent Debra A. , O'Brien Maureen Megan , Perentesis John Peter , Dasgupta Roshni 
Published: March 2020

e20007 Background: There are over 164,000 long-term survivors of Hodgkin lymphoma in the US. Awareness of the potential for preventable high risk late complications is critical for avoiding early mortality and insuring quality of life. We sought to identify key late complications in patients who had undergone staging laparotomy Methods: Retrospective review of hospital records and database of cancer survivors at our institution. Results: 95 patients with HL were identified; of these 24 patients with HL underwent staging laparotomy from 1971-1994. 18 patients had complete data available with median age at diagnosis of 13.7 years and median follow-up of 27.9 years. 16 patients underwent splenectomy, 12 patients received chemotherapy and 17 received XRT. Six patients (33%) had findings of intra-abdominal disease on laparotomy. Three patients (17%) required four repeat laparotomies for bowel obstruction more than 10 years after staging laparotomy. Of the 3 patients requiring repeat laparotomy for bowel obstruction, one had radiation to the inguinal region, one had mantle radiation (patient with 2 bowel obstructions requiring laparotomy and lysis of adhesions), and one had unknown radiation therapy history. In contrast, there were no cases of bowel obstruction in the other 71 patients who did not receive initial staging laparotomy. There were no documented cases of post-splenectomy sepsis and all post splenectomy patients received some prophylactic antibiotics. Conclusions: This is the first study to examine long term complications after staging laparotomy in a longitudinal cohort of survivors of HL. In long term follow-up, patients who underwent staging laparotomy for HL appear to have an increased incidence of repeat laparotomy, 3-4 fold higher than the expected rate of post laparotomy bowel obstruction incidence in the literature. Otherwise, the long term outcome of splenectomy in these patients appears to be very good with no episodes of post splenectomy sepsis, These findings underscore the importance of a high index of suspicion for bowel obstruction and related complications in HL survivors who had previous abdominal operative procedures. This work also underscores the importance of long term follow-up and screening in this population.
A cholesterol derivative (oxysterol; 24-ethyl-cholestane-3β, 5α, 6α-triol) with high antitumor activity against a variety of sarcomas.
Authors: Habib Nabil , Daaboul Hamid Elia , Hage Georges , Jabbour Abdo , Khalife Riad , Kassem Nader 
Published: March 2020

e20500 Background: Oxygenated derivatives of cholesterol, oxysterols, have different physicochemical properties acting on cell membranes. Agents belonging to this class of compounds have been found to induce apoptosis and to harbor antitumor activity demonstrated in vitro and in vivo. 24-ethyl-cholestane- 3β, 5α, and 6α-triol is a new oxysterol developed in our lab. Unlike other derivatives, it is, to our knowledge, the first tested in the clinic. Methods: We have previously reported encouraging and rapid results observed in patients suffering from a variety of solid tumors with an improvement of their quality-of- life and without side- effects. We have treated eight patients suffering from different types of sarcomas on a compassionate basis because we did not have any ongoing trial in sarcomas. Furthermore, most of these patients would not have been eligible for a clinical trial because of their bad performance-status. Three patients were suffering from carcinosarcomas, one from angiosarcoma, one from osteosarcoma, one from chondrosarcoma, one from undifferentiated sarcoma and one from Ewing sarcoma. Most of them were pretreated with chemotherapy and radiotherapy and most of them were in bad clinical conditions. Seven patients were females and one male with ages ranging from 21 to 82 (median age 55y). Results: None of these 8 patients experienced any side-effect despite the fact that one of them was taking a mild chemotherapy in association with oxysterol. This patient was excluded from the evaluation of the response to therapy. Among the 7 patients evaluable for response, we observed 4 complete responses (one of them confirmed by PET scan), two stable diseases and one progressive disease. The complete responses were observed in one osteosarcoma, one Ewing sarcoma, one angiosarcoma and one carcinosarcoma. As with our previous experience with this drug, no clinical or biological side-effect was observed and symptom control was achieved rapidly in all 6 symptomatic patients. Conclusions: We believe that this new compound deserves to be tested in phase II trials in patients suffering from sarcomas.
Marginal resection for osteosarcoma: Long-term outcomes.
Authors: Yamamoto Norio , Takeuchi Akihiko , Shirai Toshiharu , Hayashi Katsuhiro , Kimura Hiroaki , Igarashi Kentaro , Tsuchiya Hiroyuki 
Published: March 2020

e20505 Background: When a favorable response to chemotherapy is clinically obtained, we usually perform intentional marginal resection, which preserves the surrounding areas that are normally resected, such as ligament, nerves, blood vessels, and epiphysis region. We report on the long-term outcomes of osteosarcoma patients who underwent the combination therapy and subsequently underwent intentional marginal resection. Methods: The subjects were 43 patients with osteosarcoma. The mean age was 15 years and the mean follow-up period was 101 months. Tumors were Enneking’s surgical stage IIB in 36 patients and IIIB in 7 patients. The patients received preoperatively 3-5 courses of intraarterial fusion of caffeine combined with CDDP and ADM. The effectiveness of chemotherapy was evaluated using plain x-ray, angiography, MRI, and thallium scintigraphy. If the results of two or more imaging examinations showed effectiveness of the treatment, the patient was considered to have a complete response or partial response. Results: The treatment was effective in 14 patients (Grade III) and 29 patients (Grade IV) by histological evaluation (Rosen & Huvos) that correlated with the results of imaging evaluation. Limb function was evaluated according to ISOLS scoring system, excellent is 32 patients (74.4%), good in 7 patients (16.3%), fair in 3 patients (7.0%), and poor in 1 patient (2.3%). Local recurrence was observed in only 2 patients (4.7%). For stage IIB patients, both 5- and 10-year cumulative survival rates were 93.8%. The outcome (IIB + IIIB) was CDF in 26 patients, NED in 8 patients, AWD in 1 patient, and DOD in 7 patients. Conclusions: It is important to minimize surgical margin and to preserve healthy tissue and important structures for improving the function of the affected limb and providing optimal quality of life for the osteosarcoma patients. In the present study, intentional marginal resection was performed in osteosarcoma patients who were clinically obtained favorable responses to a combination of chemotherapy and caffeine administration. They had a good clinical course and there was no negative effect on the survival rate or local recurrence rate.
Risk of disease recurrence and mortality in gastrointestinal stromal tumor (GIST) patients receiving short-term versus long-term imatinib adjuvant therapy: A chart review analysis.
Authors: Conley Anthony Paul , Guerin Annie , Sasane Medha , Gauthier Genevieve , Schwiep Frances , Keir Christopher Hunt , Wu Eric Q. 
Published: March 2020

e20511 Background: The benefits of long-term (36 months) use of adjuvant imatinib (IM) in high risk GIST patients (pts) have been demonstrated in a recent multicenter, prospective clinical trial that compared efficacy and safety of 3 years vs 1 year IM treatment. However, in clinical practice, there is no consensus on the optimal IM treatment duration after surgery. The objective of this retrospective observational study was to compare the risk of recurrence and survival among primary resectable Kit positive GIST pts treated with adjuvant IM for a short vs an extended period of time in a real-world setting. Methods: Information on adult pts with primary resectable Kit positive GIST initiating imatinib ≤84 days after surgery was collected from 248 U.S. oncologists using an online data collection form. Detailed pt information following first GIST diagnosis, including demographic, GIST-related characteristics (e.g., risk profile), comorbidity profile, IM treatment characteristics, disease recurrence and mortality was collected for pts with short-term (6-12 months) and long-term IM use (≥24 months). Disease recurrence and mortality rates were estimated from the 1st surgery date to the 1st evidence of recurrence, mortality, or end of observation period. Multivariate Cox proportional hazard models were used to compare recurrence and mortality rates between short vs long term IM use pts. Results: Among the 246 short-term and 395 long-term IM pts, the median follow up was 884 and 963 days, respectively. The average age was similar [59.0 (10.4) vs 58.1 (9.5); p=.23] but short-term pts had less males [57.7% vs 69.6% (p<.01)] and a lower Miettinen risk score [0.3 vs 0.4, p< .01)] than long-term pts. Disease recurrence [7.3 vs 1.8%, (p< .01)] and mortality rates [6.9% vs 2.3%, (p < .01)] were also higher in short- vs long-term pts. The adjusted risk of recurrence was 4.77 times [95% CI: 1.98 – 11.48, (p<.01)] higher and mortality risk was 3.44 times [CI: 1.53 – 7.75, (p<.01)] higher in short- vs long-term pts. Conclusions: Use of IM over an extended period of time is associated with a reduction in long-term risk of disease recurrence and mortality.
Prognostic relevance of induced and spontaneous apoptosis of disseminated tumor cells in primary breast cancer patients.
Authors: Hartkopf Andreas D. , Banys Malgorzata , Gebauer Gerhard , Krawczyk Natalia , Hahn Markus , Neubauer Hans , Wallwiener Markus , Taran Florin-Andrei , Wallwiener Diethelm , Fehm Tanja N. 
Published: March 2020

e21003 Background: An imbalance between cell proliferation and programmed cell death leads to tumor growth. Although most cytostatic agents used in systemic therapy of breast cancer induce an apoptosis in tumor cells leading to their destruction, a high ratio of apoptotic cells in primary breast cancer is correlated with poor prognosis. The purpose of this study was to investigate the incidence and prognostic significance of apoptotic disseminated tumor cells (DTC) in bone marrow (BM) of primary breast cancer (PBC) patients. Methods: PBC patients who underwent primary surgery (PS) or were treated with neoadjuvant chemotherapy (NACT) between 01/2003 and 12/2007 were included into this prospective study. BM aspirates were analyzed by immunocytochemistry (M30 antibody) using ACIS system (Chromavision) according to the ISHAGE evaluation criteria. Patients without DTC in the BM were excluded from the study. Survival data were evaluated after a median follow up of 44 months. Results: BM aspirates of 383 PBC patients were analyzed. DTC were M30 positive in 82 of 298 (27%) patients who underwent PS and 41 of 85 (48%) patients treated with NACT. After NACT, the incidence of apoptotic cells in patients with complete/partial remission as compared to patients with stable/progressive disease was 63%/53% vs. 31%/0% (p=0.034). In the NACT group, M30-positive patients suffered less likely of a relapse than those without apoptotic DTC (7% vs. 23% of the events, p = 0.049). Inversely, overall survival in the PS group was significantly shorter in M30-positive as compared to M30-negative patients (75 months, 95% CI: 68-81 months vs. 84 months, 95% CI: 81-86 months; p = 0.008). Conclusions: Apoptotic DTC can be detected in breast cancer patients before and after systemic treatment. The presence of apoptotic DTC in BM of breast cancer patients can reflect the effects of neoadjuvant treatment. Spontaneous and chemotherapy-induced apoptosis may have different prognostic implications.
Activation by zoledoronic acid and IL-18 of γδ T cells from early-stage breast cancer patients in the context of helper NK cells.
Authors: Sugie Tomoharu , Murata-Hirai Kaoru , Iwasaki Masashi , Morita Craig T , Li Wen , Okamura Haruki , Minato Nagahiro , Toi Masakazu , Tanaka Yoshimasa 
Published: March 2020

e21004 Background: Human γδ T cells display potent cytotoxicity against various tumor cells pretreated with zoledronic acid (Zol). Zol has shown benefits when added to adjuvant endocrine therapy for patients with early-stage breast cancer or to standard chemotherapy for patients with multiple myeloma. Although γδ T cells may contribute to this additive effect, the responsiveness of γδ T cells from early-stage breast cancer patients has not been fully investigated. In this study, we determined the number, frequency, and responsiveness of Vγ2Vδ2 T cells from early- and late-stage breast cancer patients and examined the effect of IL-18 on their ex vivo expansion. Methods: Breast cancer patients (n=80) were enrolled after institutional review board approval and with written informed consent. Peripheral blood mononuclear cells (PBMC) were purified and stimulated with Zol/IL-2 or Zol/IL-2/IL-18 for 2 to 10 days. The expanded cells were assessed on flow cytometry and the production of IFN-γ and TNF-α measured through ELISA. Results: The responsiveness of Vγ2Vδ2 T cells from patients with low frequencies of Vγ2Vδ2 T cells was significantly diminished. IL-18, however, enhanced ex vivo proliferative responses of Vγ2Vδ2T cells and helper NK cells (CD3-CD56brightCD11c+CD14-CD16+NKGD2+NKp44low) from patients with either low or high frequencies of Vγ2Vδ2 T cells. Cell-to-cell contact between γδ T and helper NK cells appeared to promote expansion of γδ T cells. Exogenous IL-18 markedly enhanced IFN-γ and TNF-α production from PBMC stimulated by Zol/IL-2, whereas the addition of an anti-IL-18Rα mAb reduced cytokine production. Conclusions: These results demonstrate that Zol elicits immunological responses by γδ T cells from early-stage breast cancer patients and IL-18 enhances proliferative responses and effector functions of γδ T cells in the context of helper NK cells.
A gene expression signature that distinguishes malignant from benign thyroid nodules.
Authors: Tian Song , DiCarlo John , Yu Jiaye , Quellhorst George J , Blanchard Raymond K , Fahey Thomas J , Crowley Michael J , Slepushkina Nadejda , Devgan Vikram , Zeng Xiao 
Published: March 2020

e21011 Background: Thyroid nodules can be detected in as high as 67% of the population. Distinguishing thyroid cancers from benign lesions is crucial for determining an appropriate treatment plan. For years a gene expression signature for discriminating malignant from benign thyroid nodules has been sought by clinicians. In this study, multivariate bioinformatics tools were used to generate a qPCR based gene expression signature for determining malignancy in thyroid nodules. Methods: Multiple mathematical models, such as Random Forest, Support Vector Machine (SVM), and Nearest Shrunken Centroid (NSC), were used to analyze published microarray data sets and select 366 putative classifier (biomarker) mRNA targets. The selected 366 genes were further evaluated for their expression pattern by real-time PCR using a panel of 49 pathology assessed thyroid nodule samples (fresh frozen, 23 malignant and 26 benign). Results: Using the qPCR data set, Random Forest was compared with SVM and NSC classifier methods and was found to be more successful in finding genes with better discriminative powers. A Random Forest method identified a panel of 7 genes together with 5 reference genes as a gene expression signature for thyroid malignancy, which led to the development of a companion classifying algorithm to provide a probability score to assess malignancy of thyroid nodules. In our limited sample set, this signature was shown to distinguish malignant and benign thyroid nodules with 92% accuracy and 100% specificity. Conclusions: Our results suggest that a combination of multiple bioinformatics analysis tools is the proper approach for biomarker candidate selection from high-throughput gene expression data. As demonstrated here, panel of 12 genes and a companion classification algorithm has the potential to successfully discriminate malignant thyroid nodule with high accuracy and specificity. This panel of twelve genes is for molecular biology applications only.
Gene expression panel (TheraPrint) analyzed as predictors of response to neoadjuvant chemotherapy (NCT) in patients (pts) with stage II-III and inflammatory breast cancer (BC).
Authors: De Snoo Femke , Peeters Justine , Robinson Kim , Stork-Sloots Lisette , Simon Iris , Somlo George 
Published: March 2020

e21013 Background: TheraPrint is a microarray-based gene expression panel of 125 genes identified as potential targets for prognosis and therapeutic response. These genes may hold the key to a greater level of personalized prognosis and therapy for BC pts. The aim of the current study was to assess the clinical relevance of the TheraPrint genes for either predictive and/or prognostic value in 2 patient cohorts treated with NCT. Methods: The 1st patient cohort are 68 Stage II-III BC pts treated with NCT. Expression data from Agilent full genome arrays, containing the MammaPrint, BluePrint and TheraPrint diagnostic profiles/probes (Somlo et al, 2009). Median FU 2.3 years. The 2nd patient cohort are 230 Stage I-III BC pts treated with NCT. Expression data from Affymetrix probe sets was publically available (Iwamoto et al, 2011). Median FU 5.2 years. To identify genes that are differentially expressed between responders (pCR/RCBI) and non-responders, a supervised analysis was performed. The analysis was performed across all pts and also within groups of HER2+ and HER2-. Univariate t-tests were performed, with results filtered by permutation p-value (p<0.05) and fold change of >1.5. Global test was also reported. In addition, survival data analysis was performed across all pts. Results: Overlapping genes between the 2 datasets that were significantly differentially expressed between responders and non-responders include: BCL2 (down-regulated) and CDH3, GRB7, KRT6B, KRT17 (up-regulated). When analysing the HER2- subgroup, 3 genes turned out to be differentially expressed between responders and non-responders in the 2 datasets: FLT1, PIK3R1 (down-regulated) and KRT6B (up-regulated). For the HER2+ subgroup, only one gene overlapped for the 2 datasets: IL2RA (up-regulated). The top canonical pathways for the significant genes have been analyzed, and in addition correlation of the TheraPrint gene expression with survival for these pt groups. Conclusions: This study has identified several genes from a panel of 125 TheraPrint genes with statistically significant correlation between expression and response to NCT.
Risk of venous thromboembolism in cancer patients treated with cisplatin: A systematic review and meta-analysis.
Authors: Seng Sonia Maria , Liu Ziyue , Chiu Sophia , Proverbs-Singh Tracey , Sonpavde Guru , Choueiri Toni K. , Tsao Che-Kai , Yu Menggang , Hahn Noah M. , Oh William K. , Galsky Matt D. 
Published: March 2020

e21016 Background: Several reports suggest that cisplatin is associated with an increased risk of thromboembolism (TE). However, patients with solid tumors have multiple risk factors for TE and the excess risk of venous thromboembolic events (VTEs) with cisplatin-based chemotherapy as compared with non-cisplatin-based chemotherapy has not been well described. We performed a systemic review and meta-analysis of randomized controlled trials (RCTs) evaluating the incidence and risk of VTE associated with cisplatin-based chemotherapy. Methods: PubMed was searched for articles published from January 1, 1990 until December 31, 2010.The primary aim was to evaluate the association between treatment with cisplatin and VTEs in patients with cancer. Clinical trials that met the following criteria were included in the meta-analysis: (1) prospective randomized phase 2 and 3 trials of patients with cancer; (2) randomization to treatment with cisplatin versus a non-cisplatin containing chemotherapy regimen (3) available data on venous thromboembolic events. Data on all grade venous thromboembolic events was extracted. Study quality was calculated utilizing Jadad scores. Incidence rates, relative risks, and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses included the impact of publication year, tumor type, and cisplatin dose. Results: A total of 8216 patients with a variety of advanced solid tumors from 38 RCTs were included for analysis. Among patients treated with cisplatin-based chemotherapy, the summary incidence of VTE was 1.64% (95% CI, 1.06–2.25). Patients treated with cisplatin-based chemotherapy had a significantly increased risk of VTE with a relative risk of 1.65 (95% CI, 1.25–2.18; P = .01) compared with controls. Exploratory subgroup analysis revealed the highest relative risk of VTE in patients receiving a weekly equivalent cisplatin dose >30 mg/m2 (2.64; 95% CI, 1.18–5.77; P = .02) and in studies reported during 2000-2010 (1.70; 95% CI, 1.27–2.28; P = .01). Conclusions: Cisplatin chemotherapy is associated with a significant increase in the risk of VTE in patients with advanced solid tumors compared with non-cisplatin chemotherapy.