bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical response to imatinib mesylate in recurrent and metastatic gastrointestinal stromal tumors
Authors: Villalobos R. , Hernández G. , Martinez-Prieto M. , Silva A. 
Published: March 2020

20528 Background: We analyzed the efficacy and safety of imatinib mesylate in GIST (Gastrointestinal Stromal Tumors) in various anatomic sites. Methods: Out of 24 patients with recurrent or metastatic disease receiving treatment, clinical and tomographic evaluation was possible only in 21 pts. RECIST criteria were used to evaluate response and NCI guidelines were used for evaluation of toxicity. The treatment given between March 2003 and December 2006 was imatinib mesylate 200mg twice daily until disease progression or drug intolerance. All included patients had histopathologic confirmation and CD 117 positive inmunohistochemistry. Results: Patient characteristics were as follows: 19 females, 2 males, average age: 37.8 years (range: 36 - 80), Functional status according to ECOG: 0 in 19 pts, 1 in one patient and 3 in one patient. Anatomic sites were: 4 stomach, 7 small intestine, 3 rectum-sigmoid, 4 carcinomatosis from unknown primary, 2 peripancreatic and one esophageal. Nine patients had recurrent disease, 12 unresectable disease and 11 pts had liver metastases and 13 had retroperitoneal metastatic disease. Comorbidities: 3 pts with Type 2 Diabetes Mellitus one patient with Systemic Hypertension, and deep vein thrombosis each, two patients with a previous diagnosis of cancer: Thyroid and Lung Cancer respectively. Responses:2 (9.5%)CR, 6 (28.5%) PR, 12 (57.1%) stable disease, one (4.7%) pt. with progressive disease. Toxicity: one patient had rash, one patient presented bone pain, one patient with face discoloration, one with cephalea and nausea, and two patients with bipalpebral edema. Median duration for response was 5.7 months (range 2–30) at the moment. Conclusions: Efficacy of imatinib mesylate in recurrent and metastatic GIST's is high with overall response rates of 95% and adequate tolerance. Studies as adyuvant and second line therapy are needed in our population. No significant financial relationships to disclose.
Phase II trial of imatinib mesylate and hydroxyurea for adults with recurrent/progressive low-grade glioma
Authors: Bota D. A. , Desjardins A. , Quinn J. A. , Rich J. N. , Vredenburgh J. J. , Sathornsumetee S. , Goli K. , Salvado A. , Friedman H. S. , Reardon D. A. 
Published: March 2020

2053 Background: We evaluated the combination of imatinib mesylate and hydroxyurea in recurrent/progressive low-grade gliomas (LGG) following the encouraging response of this combination demonstrated among adults with recurrent malignant glioma. Methods: Key eligibility criteria: age over 18 yrs; histologically confirmed grade II LGG that is recurrent/progressive following at least prior surgical resection; Karnofsky = 60% and adequate organ function. Imatinib plus hydroxyurea were given on a continuous oral daily schedule for 28 day cycles; imatinib was administered at 400 mg daily to patients not on CYP3A-enzyme inducing antiepileptic drugs (EIAED) while those on EIAED received 500 mg twice a day. All patients received 500 mg twice a day of hydroxyurea. Patients were evaluated every other month with physical and MRI examinations. Results: Twenty-seven patients with recurrent or progressive LGG have enrolled including 17 with astrocytoma and 10 with oligodendroglioma. Eleven (40.7%) are on EIAED. Median age was 42 years (range 24–66 years). 26% of patients had received prior therapy other than surgery (XRT, n=2; chemotherapy, n=5). The most frequent toxicities possibly related to the study regimen were fatigue (grade 2, n=5; grade 3, n=1), neutropenia (grade 2, n=1; grade 3, n=2), anemia (grade 2, n=2), rash (grade 2, n=2), nausea (grade 3, n=1), anorexia (grade 2, n=1), and AST elevation (grade 2, n=1). There were no grade 4 or 5 treatment-related toxicities. Among patients evaluable for response, 17 (85%) achieved stable disease and 3 (15%) had progression. Twenty patients continue on study having received 2–16 months of therapy. Additional accrual and follow-up is ongoing. Conclusions: Continuous daily treatment of imatinib plus hydroxyurea is well tolerated and associated with encouraging preliminary activity among adults with recurrent/progressive LGG. [Table: see text]
High grade unclassified sarcoma of the broad ligament: A case report and literature review
Authors: Mauricio D. D. , Vanderlee G. 
Published: March 2020

20536 Background: The incidence of primary sarcoma of the broad ligament is very rare. From the first reported finding in 1968, there are only 17 documented cases worldwide of this very progressive and highly malignant gynecologic neoplasm. We present the 18th case of this aggressive tumor to add to the scarce knowledge about this disease and to contribute in characterizing its behavior and its reasonable management. Methods: Case report and case review/series Results: This is the 18th case of broad ligament sarcoma found on routine physical examination in a woman who had previous hysterectomy for benign leiomyoma. Treatment consisted of resection of the broad ligament mass, bilateral salpingo-oophorectomy, omental and peritoneal biopsies with pelvic cytology. She is disease-free on strict clinical surveillance. An updated extensive review of previous reports was done as well. Conclusions: The scarcity of the cases of leiosarcoma of the broad ligament prevents the understanding of its biologic nature. Thus, there were different approaches on its staging, surgical management and adjuvant therapy, and tumor surveillance producing unpredictable prognosis. It appears TAH-BSO with rigid disease follow-up and subsequent chemotherapy or radiotherapy prolongs survival. No significant financial relationships to disclose.
Plasma pharmacokinetics and cerebrospinal fluid concentrations of erlotinib in high-grade gliomas: A novel, phase I, dose escalation study
Authors: Buie L. W. , Lindley C. , Shih T. , Ewend M. , Smith J. K. , Skelton M. , Kwock L. , Morris D. , Tucker C. , Collichio F. 
Published: March 2020

2054 Background: Erlotinib (ERL) is an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. EGFR is overexpressed in glioblastoma multiforme (GBM). The primary objectives of this study were to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT) and to evaluate plasma and cerebrospinal fluid (CSF) ERL concentrations using a novel every 72 hour ERL dosing schedule. Methods: Patients = 18 years of age with GBM or high grade glioma with evidence of disease progression following first line therapy (surgery/XRT/chemotherapy) and Karnofsky performance status = 60 % were included. Patients were stratified based on use of enzyme-inducing antiepileptic drugs (EIAED). Patients not on EIAED were initiated on ERL 450 mg PO every 72h, while those on EIAED were initiated on 900 mg PO every 72 h. Results: Six patients have been enrolled and assessed for safety, 5 for plasma PK and 3 for CSF concentrations. For ERL, the area under the plasma concentration versus time curve (AUC) was greater and the half-life longer in patients not receiving EIAED. However, the AUC of OSI-420, the major metabolite of ERL, was lower in patients not receiving EIAED. The OSI-420 AUC: ERL AUC ratio was increased 3 fold among patients receiving EIAED, indicative of increased hepatic metabolism and increased clearance. CSF concentrations were detectable and ranged from 1 to 3% of peak plasma concentrations. Neither group has experienced a DLT or reached the MTD. The most common side effects (grade 1/2) have been diarrhea (83%), rash (100%) and fatigue (33%). To date, there has been 1 partial response, 1 patient with stable disease and 4 patients with disease progression. The partial response and stable disease have occurred in patients with GBM. Conclusions: ERL is a well tolerated therapy. Patient enrollment and subsequent dose escalation is ongoing and updated results will be presented at the ASCO 2007 meeting. [Table: see text] No significant financial relationships to disclose.
Pegylated liposomal doxorubicin in recurrent high-grade glioma: Comparison of clinical trial results and compassionate use
Authors: Glas M. , Koch H. , Hirschmann B. , Jauch T. , Steinbrecher A. , Bogdahn U. , Hau P. 
Published: March 2020

2073 Background: Results from prospective clinical studies may not always be reproduced in clinical practice. Therefore it is important to compare data from clinical trials with data from compassionate use of the same treatment. Here, we present patients with relapsed high-grade glioma treated outside a clinical trial with liposomal pegylated doxorubin (PEG-DOX). Methods: This data was documented prospectively and compared to our earlier published study results. Forty-nine patients with recurrent high-grade glioma (WHO III: n=18; IV: n=31) were treated with PEG-DOX (days 1 and 14/28, 20 mg/m2) alone or in combination therapy with temozolomide (TMZ) (days 1 to 5/28, 200 mg/m2). The clinical response rate, time to progression, progression free survival and overall survival were evaluated. Results: The overall response rate including disease stabilization was 53% (WHO III: 61; IV: 48). PFS-6 was 27% (WHO III: 33%; IV: 23%). The median OS after initiation of PEG-DOX was 35 weeks (WHO III: 68; IV: 31). Comparison of PEG-DOX monotherapy and combination therapy revealed no significant difference. Both regimens were well tolerated, with the main side effect being hematologic toxicity (grade 1–2: 8%, grade 3–4: 18%). Conclusion: These data compare favorably with published data and underline the potential of PEG-DOX in this setting. In addition, the prolonged median OS after initiation of PEG-DOX for grade III-tumors (68 weeks) merits additional focus. No significant financial relationships to disclose.
Correlation between VEGF expression and MVD in sporadic and NF2-related schwannomas
Authors: Ditomaso E. , Stemmer-Rachamimov A. , Potts A. , Drottar M. , Jain R. K. , Plotkin S. R. 
Published: March 2020

2083 Background: Neurofibromatosis 2 (NF2) is a tumor suppressor syndrome characterized by the presence of bilateral vestibular schwannomas (VS) and multiple meningiomas for which alternative treatments are desperately needed. Currently there are no well- tolerated agents that are clinically active. Previous groups have shown VEGF expression in small series of VS. In this study, we expand these findings and show a significant relationship between VEGF bound to the vascular endothelium and microvascular density (MVD) in NF2-related VS. This observation providing a strong rationale for the use of VEGF blockade in this patient population. Methods: Formalin-fixed, paraffin-embedded specimens were obtained from surgical resections of 22 patients with sporadic VS and from 21 patients with NF2 VS. Sections were stained with anti-VEGF polyclonal antibody and with anti-CD31 monoclonal antibody. Intensity of immunostaining of tumor cells for VEGF was scored in semi-quantitative fashion (0-none, +1-mild, +2-moderate, +3-strong); MVD was calculated by averaging the number of CD31-positive vessels in 5–15 high -powered fields (20x). MVD in tumors with and without VEGF bound to the vascular endothelium were compared using t-test. Results: Expression of VEGF was detected in all sporadic and NF2 VS. Strong expression of VEGF in tumor cells was more common in sporadic VS (45%) than in NF2-related VS (5%). In contrast, endothelial-bound VEGF was more common in NF2- related VS (75%) than in sporadic VS (45%). There was no difference in mean MVD between sporadic (6.2%) and NF2-related tumors (6.1%). However, in NF2-related VS, MVD was significantly greater in tumors with endothelial bound VEGF (7.4%) than without (4.6%) (p < 0.05). Conclusions: VEGF expression in tumor cells was universal in this series of sporadic and NF2-related VS. Although the intensity of VEGF expression appears greater in sporadic tumors, endothelial- bound VEGF is more common in NF2-related lesions and is associated with greater MVD. This finding indicates a potential activity of the VEGF angiogenic pathway in this patient population. Therefore anti-VEGF therapy, such as bevacizumab, sunitinib, or sorafinib, represents a rationale approach to treating NF2 patients with VS in which surgical approach is not possible or has failed. No significant financial relationships to disclose.
Analysis of MGMT promoter methylation status in high grade glioma patients with long term and conventional survival times: A retrospective study
Authors: Preusser M. , Hassler M. , Elandt K. , Gelpi E. , Hainfellner J. , Baur M. , Marosi C. 
Published: March 2020

2084 Background: Response to alkylating chemotherapy in patients with high grade gliomas (HGG) has been found correlated to epigenetic silencing of the DNA repair gene MGMT (O6-methylguanine-DNA methyltransferase) in the tumor tissue. Patients with HGG expressing a methylated MGMT promoter benefited from alkylating chemotherapy in terms of a prolonged survival as compared to patients with unmethylated MGMT promoter. Methods: Our study cohort comprised 47 patients with HGG, all treated with concomitant chemotherapy and radiotherapy in our institution. 23/47 patients (8 women, 15 men, aged 22.4–64.5 years, median 36.3) survived longer than 36 months (range of survival times 36–137 months, in median 46.9 months) and were defined as long term survivors (LS). 24/47 patients (5 women and 19 men, aged 18.3–73.3 years, median 47.7) with early tumor relapse who survived in median for 23.5 months were defined as HGG patients with conventional survival (CS). In all cases, we extracted DNA from formalin-fixed and paraffin-embedded tumor tissue samples. The methylation status of the MGMT promoter was determined by bisulfide modification of the DNA and methylation-specific polymerase-chain- reaction (MSP). MSP results were rated by 4 independent observers. Results: There was high interobserver agreement at interpretation of MSP results (range of kappa values: 0.71–0.87). Among LS, we found MGMT promoter methylation in 13/24 (81.5%) patients and an unmethylated MGMT promoter in 3 patients, whereas the MSP results were not interpretable in 7 patients of this patient subgroup. Among CS, we found promoter methylation in 16 patients (66.6%), unmethylated promoter in 6 patients and uninterpretable results in one patient. There was no statistically significant difference in MGMT promoter methylation rate between LS and CS. Conclusions: The proportion of gliomas with methylated MGMT promoter in this series is unexpectedly high, particularly for CS patients. Potential explanations for this finding are methodological differences due to the use of paraffin-embedded tumors instead of frozen tumor material as in most published series and a potential random accumulation of MGMT positive tumors in the patients with CS survival. No significant financial relationships to disclose.
Prognosis of sub-types of cancer of unknown primary (CUP) compared to metastatic cancer
Authors: Bishop J. F. , Tracey E. , Glass P. , Jelfs P. , Roder D. 
Published: March 2020

21010 Background: The aim is to study the clinical characteristics and outcomes of a complete cohort of presentations of Cancer of Unknown Primary (CUP) compared with patients presenting with metastatic cancer of known primary site. Methods: All persons diagnosed with cancer in New South Wales, Australia, from 1980 to 2004 were studied using a population based cancer registry. Patients classified as CUP were documented, compared to those with initial metastatic presentations of a known primary, for the same period. Results: There were 65,239 histologically or cytologically confirmed metastatic cancers presented. Of these 46,435 (77%) were metastatic with a known primary site and 13,280 (22%) were CUP. The median survival (ms) of all patients presenting with CUP was 3 months compared with 7 months for metastatic cancers of known primary site (p<0.0001). Patients with CUP with adenocarcinoma had significantly worse prognosis compared to metastatic adenocarcinoma of known primary site. However patients with squamous cell CUP had a significantly better outcome (ms 12 months) than metastatic squamous histology with a known primary site (ms 5 months, p<0.0001) with 31% of squamous cell CUP alive at 6 years. For those with CUP and adenocarcinoma the risk of dying was 80% greater compared to those with a known primary and adenocarcinoma (HR 1.8 95%CI 1.7–1.8). For those with CUP and squamous cell carcinoma the risk of dying was 50 % less (HR 0.49 95%CI 0.46–0.53). CUP with small cell, (HR 0.77 95%CI 0.71–0.85) and undifferentiated histology (HR 0.84, 95%CI 0.76–0.93) after controlling for sex and age, had a significantly better prognosis than other metastatic cancers. Germ cell CUP represented only 0.2% of all CUP presentations. Conclusions: CUP is a heterogeneous classification of cancer with a poorer prognosis overall when compared to metastatic cancer of known primary site especially if adenocarcinoma. However, squamous cell and small cell CUP had a better prognosis suggesting a need for specific and more focused treatment. Lack of trends for less CUP presentations compared to reducing metastatic cancer over this 24 year period suggests that CUP is in part a distinct clinico-pathological entity rather than a missed primary diagnosis. No significant financial relationships to disclose.
Low Foxp3 cells infiltrate is a marker of pathological complete response to neoadjuvant chemotherapy in breast carcinoma
Authors: Ladoire S. , Arnould L. , Apetoh L. , Coudert B. , Martin F. , Chauffert B. , Fumoleau P. , Ghiringhelli F. 
Published: March 2020

21011 Background: T cell infiltration is associated with tumor prognosis in many cancer types. To assess the capacity of neoadjuvant chemotherapy to impact on T cell infiltration in breast cancer, we investigated if pathological complete response (pCR) to neoadjuvant chemotherapy correlated with T cell infiltration Methods: CD3, CD8 and Foxp3 positive cells were detected by immunohistochemistry in a series of 56 breast cancer patients treated by neoadjuvant chemotherapy. Infiltrates were analysed before and after the end of the treatment. Cytotoxic cells were stained using anti-Granzyme b and TiA1 antibodies Results: Poor prognosis factors (negative hormonal receptors, high tumor grade and nodal involvement) correlated with a significant higher number of CD3, CD8 and Foxp3 cells infiltrates before chemotherapy. Chemotherapy only induced a decrease in the number of Foxp3 cells (p<0.01) while the level of CD8 and CD3 cells were maintained (p=0.8). pCR were observed in 12 patients who had a drastic decrease of Foxp3 positive cells (mean:1.6±1.4 versus 0.08 ± 0.2; p<0.001) while these cells remained elevated in non responders (mean: 1.5±1 versus 1 ± 1 p=0.2). Furthermore, using a cutoff criterion that combined high CD8 infiltration and no Foxp3 cell infiltration on surgical specimens we could predict pCR with a sensitivity of 75% and a specificity of 93%. Cytotoxic effector cells infiltrate was only enhanced in pCR. In multivariate analysis, only high tumor grade and low Foxp3 cell infiltration on final histological specimens were independent predictors of a pCR (HR (95% CI): 17,7394 (1,1 to 272,5) p=0.04 and 0,0132 (0,0002 to 0,9) p=0.04 respectively). The Kaplan Meier estimate of metastasis-free survival indicated a trend toward higher percentage of metastases-free patients in pCR and combined immunological criterion (Log rank test, p=0.1 and p = 0.12 respectively) Conclusions: These findings indicate that pathological complete response to neoadjuvant chemotherapy is associated with an immunological profile consisting in absence of immunosuppressive Foxp3 cells, presence of high number of CD8 T cells, and an increased number of cytotoxic cells. These results argue for the induction of an antitumor immune response by chemotherapy in this group of patients No significant financial relationships to disclose.
Molecular markers expression in mediastinal nodes from resected stage I non-small cell lung cancer (NSCLC): Prognostic impact and potential role as markers of occult micrometastasis
Authors: Massuti B. , Galbis J. , Alenda C. , Peiró F. M. , Martí J. , Baswitch B. , Rodriguez-Paniagua J. M. , Rosell R. , Taron M. , Benlloch S. 
Published: March 2020

21016 Background: 5-y surv in surgically resected St I NSCLC is 60–70% whereas in cases with affected lymph nodes (LN) it is < 50%. The main risk factor for recurrence is nodal disease. Current histopathologic analysis can miss occult micrometastases in nodal tissues at initial diagnosis. Detection of micromets with a more sensitive technique would be useful to define a high-risk population selecting patients (p) for postop treatment. We assessed the role of several genes mRNA expression in pathological negative LN from resected St I NSCLC p as markers of occult micromets and correlated the results with relapse, and survival. Methods: Paired tumor and histological negative LN (n=344) obtained by systematic mediastinal lymphadenectomy from 38 surgically resected St I NSCLC p were analyzed for the presence of 12 genes mRNA expression using RT-Q-PCR in an ABIPRISM 7500. RNA was extracted using ABIPRISM 6100. Specifically designed primers and probes were purchased from Applied Biosystems as Assay-on-demand; GADPH was used as an endogenous control. Samples were also analyzed by ICH for LN staging. Results: 38 NSCLC p; 12 adenoca, 16 squamous cell, 10 undifferentiated . From the 12 tested genes CEA and PLUNC were found with high expression in lung tissue and low or null expression in normal LN. We consider molecular + LN those in which expression of CEA or PLUNC was detected. In the 344 pathological negative LN, 13% (44/344) were positive for CEA, 16% (54/344) for PLUNC. The expression patterns were similar for both markers. At a median follow-up of 24 mo (9–46) 11 p had died from NSCLC and 1 had died without recurrence. None of the living p had tumor recurrence. For the prognostic assessment, molecular + LN were classified as N1 and N2. Median DFS was 15 ± 11.74 mo in p with N2 molecular + nodes was and has not yet reached in cases of molecular (-) LN (p=0.028). Median survival of p with N2 molecular positive nodes was 17.3 ± 5.7 mo and has not yet reached (p= 0.0083) for molecular (-) LN. Conclusions: CEA and PLUNC mRNA expression could be used as molecular markers of occult micrometastases in mediastinal LN showing a prognostic effect . CEA and PLUNC expression provides a tool for selecting high-risk p considered for adjuvant therapies No significant financial relationships to disclose.