bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial of temozolomide and vinorelbine for patients with recurrent brain metastases
Authors: Iwamoto F. M. , Omuro A. M. , Raizer J. J. , Nolan C. P. , Hormigo A. , Lassman A. B. , Gavrilovic I. T. , Abrey L. E. 
Published: March 2020

2050 Background: Temozolomide has shown modest efficacy in the treatment of recurrent brain metastases. We designed a regimen combining temozolomide with vinorelbine, a lipophilic agent that crosses the blood-brain barrier, trying to improve efficacy. Methods: This is a phase II trial with 28-day cycles using temozolomide (150 mg/m2, days 1–7 and 15–21) and vinorelbine on days 1 and 8. We previously reported a phase I trial that established an MTD of 30 mg/m2 of vinorelbine in this combination, but the dose was decreased to 25 mg/m2 in this phase II trial. The phase II component was planned as a two-stage clinical trial. Since two or more responses were observed after the 20 initial patients, 15 more assessable patients were required. This design had a 91% probability to detect a true response rate of 20% or more. The primary endpoint was objective radiographic response. Secondary endpoints include OS, PFS and toxicity. Patients = 18 years old with KPS = 60, adequate organ function and progressive or recurrent brain metastases were eligible. Results: Thirty-six patients (13 men, 23 women) with a median age of 56 years (range, 38–76) and median KPS of 80 were enrolled. The primary tumor sites were lung (n=19), breast (n=11), colon (n=2), bladder (n=1), endometrium (n=1), head/neck (n=1) and kidney (n=1). Prior therapies included whole-brain radiation therapy (81%), chemotherapy (97%), radiosurgery (42%) and brain metastasis resection (47%). Objective radiographic response was 7% (1 CR and 1 minor response); 4 patients had SD and 23 PD. Three patients withdrew consent and did not undergo follow-up scans, 2 patients did not receive the planned treatment and 2 patients recently began treatment and have not been assessed. The median follow-up was 12.3 weeks and 72% of patients have died. Median PFS and OS were 8.3 weeks and 5 months, respectively. Grade 3/4 toxicities were mainly hematological and 3 patients were removed from the study due to myelosuppression. Conclusions: In this heavily pretreated population of patients with brain metastases, adding vinorelbine to temozolomide does not seem to improve response rates as compared to temozolomide alone. Single-agent temozolomide also has a more favorable toxicity profile. [Table: see text]
The use of in-vitro drug resistance levels as a predictor of outcome in soft tissue sarcoma
Authors: Schleicher L. , Hesdorffer M. , Taub R. 
Published: March 2020

20510 Background: We have assayed in-vitro drug resistance and immunohistochemical staining for drug resistance markers (MDR-1, MRP) in patients with metastatic soft tissue sarcoma patients. We looked at resistance to Cisplatin, Doxorubicin, and Ifosphamide, prior to beginning chemotherapy. The aim of this study was to investigate the validity of in-vitro drug resistance testing as a predictor of outcome. Methods: Viable tumor samples obtained at time of recurrence or metastasis from 13 patients with metastatic soft tissue sarcoma were tested by a semiquantitative 12 hour tritiated-thymidine uptake cell-proliferation assay (EDR test, Oncotech Inc., Tusin, California) for resistance to the chemotherapy drugs cisplatin, doxorubicin, and ifosphamide. The mean drug resistance level for these three drugs was plotted against survival in months, both from time of metastasis and time of initiation of chemotherapy. Mean resistance was also correlated with positive staining for either MDR-1 or MRP. Results: There was no relationship found between the mean drug resistance and survival, either from time of metastasis (correlation coefficient -0.0596) or time of initiation of chemotherapy (correlation coefficient - 0.1864). There was no correlation between mean drug resistance and; 1) presence of MDR-1 staining (correlation coefficient -0.1269), 2) presence of MRP staining (correlation coefficient -0.2175), 3) presence of either staining for MDR-1 or MRP (correlation coefficient -0.2636). Conclusions: 1) In-vitro drug resistance is not predictive of outcome in patients with soft tissue sarcoma. 2) There is no correlation between the mean drug resistance and positive staining for either MDR-1 or MRP. No significant financial relationships to disclose.
Contrast-enhanced ultrasonography (CEUS) in retroperitoneal liposarcomas
Authors: Brandi M. , Badalamenti G. , Sorrentino F. , Vizzini L. , Incorvaia L. , Rinaldi G. , Sanfilippo M. , Gebbia N. , Intrivici C. , Caruso G. 
Published: March 2020

20514 Background: CEUS with second-generation contrast agents has been proposed to monitor tumor response to imatinib in patients with metastatic GIST. There are no data in patients with other sarcomas. Our aim was to assess the value of CEUS as a marker of tumor response in retroperitoneal liposarcoma, in addition to its ability to render the baseline malignancy grade of the disease. Methods: CEUS was performed after a SonoVue injection (Bracco, Milano, Italia). SonoVue is a suspension of microbubbles of exafluoride sulphure gas (average diameter 3 μm) with a phospholipidic shell. A low mechanical index (MI<0.09) was used in order to minimize microbubbles rupture. Ultrasound device systems (Philips ATL HDI 5000, Bothel, Washington) with a broandband probe (2–5 Mhz) and specific contrast agent algorithms (Pulse Inversion Harmonic Imaging) were used. The use of this algorithm allowed a real time imaging of all vascular phases (arterial, portal and late). All patients underwent CT scan, PET tomography and routine blood examinations. Ten patients with retroperitoneal liposarcomas were enrolled in this study (5 high grade, 3 intermediate grade, 2 low grade). Results: Five males and five females with metastatic or relapsed disease were enrolled. Median age was 57 years (range 40–70). All underwent chemotherapy with Ifosfamide and Doxorubicin. In all patients there was a clear correlation between contrast enhancement and grading: in low-grade patients there was no contrast enhancement, while the highest level of enhancement was seen in undifferentiated sarcomas. With regard to tumor response to chemotherapy, only 4 patients were evaluable. One patient had a PR and 3 patients had PD. In the 3 patients with PD CEUS showed contrast enhancement, PET was uptaking, but CT scan did not detect any change. In the patient with a PR, strong decrease of tumor perfusion on CEUS and uptaking on PET was seen, again with no change on CT scan. Conclusions: These preliminary observations suggest that CEUS may be more useful than CT scan on assessing tumor response in retroperitoneal sarcomas, and may predict the baseline malignancy grade. Data on a larger number of patients will be presented. No significant financial relationships to disclose.
Endosialin/TEM1: Cellular localization and prevalence in soft-tissue tumors and carcinomas
Authors: Rouleau C. , Weber W. , Bagley R. , Morgenbesser S. D. , Kataoka S. , Honma N. , Hasegawa K. , Ishida I. , Thurberg B. L. , Teicher B. A. 
Published: March 2020

20520 Background: Tumors grow more slowly in endosialin/TEM1 KO mice compared to WT, suggesting that host endosialin/TEM1-positive stroma promotes malignancy (Nanda, PNAS, 2006). Methods: We surveyed 92 human clinical samples by IHC (52 epithelial tumors, 40 sarcomas) to measure the extent of endosialin/TEM1 expression and assess cellular localization. Expression was also studied in primary cell cultures and 49 cancer lines. Results: 46/52 adenocarcinomas and carcinomas (88.5%) expressed endosialin/TEM1 mainly in pericytes (7/7 bladder, 7/11 breast, 5/5 colon, 7/8 ovarian, 7/7 renal, 2/2 liver, 4/5 lung, and 7/7 gastric). In some tumors, endosialin/TEM1 was present in pericytes and in fibroblasts (2/7 bladder, 4/11 breast, 5/5 colon, 5/8 ovarian, 2/7 renal, 2/2 liver, 1/5 lung and 7/7 gastric cancers). 32/40 sarcomas (80%) expressed endosialin/TEM1 mainly in pericytes (10/11 synovial sarcomas, 9/10 malignant fibrous histiocytomas, 3/5 Ewing's sarcomas, 3/5 angiosarcomas, 3/4 rhabdomyosarcomas, 2/2 pleiomorphic sarcomas, 1/1 Kaposi's sarcoma, 0/1 leiomyosarcoma and 1/1 liposarcoma). Synovial sarcomas displayed intense fibroblast staining. Endosialin/TEM1 was expressed by sarcoma cells in a few samples. In culture, we previously showed expression in human fibroblasts, endothelial precursor cells, pericytes and mesenchymal stem cells (MSC). We now report that endosialin/TEM1 mRNA is present in MSC during osteogenic and adipogenic differentiation. In 49 human tumor lines, expression was restricted to sarcoma cells (7/15 sarcoma, 0/5 melanoma, 0/2 neuroblastoma, 0/4 breast, 0/1 ovarian, 0/3 prostate, 0/1 renal, 0/1 liver, 0/3 pancreatic, 0/6 colorectal and 0/8 hematopoietic cancer lines). Conclusions: Endosialin/TEM1 is frequently expressed in clinical cancer (85% of 92 samples), both in epithelial and mesenchymal tumors. Cellular expression is mesenchymal in clinical samples and in culture. In tissues, endosialin/TEM1 is present in pericytes and fibroblasts, with some expression in sarcoma cells. The importance of endosialin/TEM1-positive stroma in experimental animals and prevalence in patient samples warrant further investigation. Endosialin/TEM1 may be a useful therapeutic target. [Table: see text]
Multivisceral resections of gastrointestinal stromal tumors
Authors: Zhou Y. , Du C. , Fu H. , Zhao G. , Shi Y. 
Published: March 2020

20523 Background: Gastrointestinal stromal tumors (GISTs) with positive kit staining, although rare, are the most common mesenchymal neoplasms affecting the gastrointestinal tract. We present our experience in the treatment of disease involving adjacent organs with multivisceral resections. Methods: The clinicopathologic records of twenty-two patients with multivisceral resection, among 170 patients suffered from GISTs treated in our hospital from 1994 to 2005, were retrospectively reviewed. Nine primary tumors originated from the stomach, 4 from the small intestine, 6 from the colorectum, 1 from abdominal cavity, and 2 from the retroperitoneal area. Meanwhile complete follow-up records were available in 15 patients with median 5-year follow-up. Results: The patients included 9 men and 13 women, from 36 to 77 year old. The largest tumor diameter ranged from 2 to 20 cm. The types of multivisceral operation comprised splenectomy (n=8), coloectomy (n=6), nephrectomy (n=5), partial hepatectomy (n=1), duodenectomy (n=1), oophorectomy (n=1), pancreatectomy (n=1), and adrenalectomy (n=1). None of lymph node metastatsis was found in 7 patients with lymph node dissection with gastric GISTs (n=5) or small intestinal GISTs (n=2). The involved organs confirmed by the pathologic diagnosis included kidney (n=2), spleen (n=2), pancreas (n=2), mesentery (n=1), and omentum (n=1). There was no perioperative mortality in this series. Among follow up patients, 9 were alive and 5 were died from the tumor recurrence or metastasis. Among them, one person with gastrectomy, pancreatectomy, adrenalectomy is still alive under 2 year follow-up by imatinib mesylate therapy postoperatively. Conclusions: Complete surgical resection with a negative gross margin by en bloc resection of the involved organs remains the standard treatment for non-metastatic GISTs. Imatinib mesylate represents a major breakthrough in the treatment of advanced GISTs and is the first effective systemic therapy for the disease. No significant financial relationships to disclose.
Clinico-pathologic pattern of gastrointestinal stromal tumors (GIST) in southern India: A single-institution experience
Authors: Lamba M. , Mukherjee G. , Saini K. , Ramachandra C. , Rao C. , Kumar R. , Bapsy P. , Babu K. , Attili S. , Batra U. 
Published: March 2020

20531 Background: There have been major advances in understanding the behavioral pattern, pharmacological intervention, and clinical response of GIST; yet Indian data in this regard is sparse. This study analyses the clinico-pathologic features in 36 patients (21 male, 15 female) of GIST seen at our institution. Methods: GIST was defined as a mesenchymal spindle or epithelioid cell lesion arising in the GI tract with CD117 immuno-reactivity. Retrospective data from January 03 to March 06 was analyzed for age, tumor site, morphology, immuno- reactivity, prognostic factors, response to treatment (by RECIST), and recurrence or metastasis. All patients had surgery; those with residual, recurrent, or metastatic disease got imatinib till tumor progression. Results: GIST presented at a mean age of 48.2 yrs (SD 6.4, range 34–65). The mean tumor size was 13.9 cm (range 2–42). The most common site was the small intestine (ileum 8, jejunum 7, duodenum 4). 24 patients (66.7%) had localized disease at baseline. Of these, 14 had local recurrence after surgery, and were given imatinib. 5 of them are in complete remission, 4 had partial response (PR), 3 patients died, and 2 had stable disease. Most patients with recurrent GIST had a mitotic rate of >10/50hpf. 8 patients developed metastasis, and received imatinib. Of these, 2 got a PR, 3 had progressive disease and died, and 3 had stable disease. 12 patients (33.3%) had metastasis at baseline (to liver and abdominal cavity), and underwent debulking. Of these, 6 patients with stable disease are on treatment with imatinib, 3 died and 3 were lost to follow-up. Conclusions: Average age of presentation was less than in Western reports. The commonest site was the small intestine as opposed to stomach in western literature. Mitotic rate was a better prognostic factor than gross tumor size. GIST with a mixed cell morphology showed aggressive behavior. Imatinib mesylate is useful in the post-operative management of GIST. [Table: see text] No significant financial relationships to disclose.
Single center phase II trial analysing the role of imatinib/hydroxyurea in patients (pts) with pretreated non-progressive glioblastoma (GBM) as maintenance treatment
Authors: Dresemann G. , Hosius C. , Nikolova Z. , Letvak L. 
Published: March 2020

2055 Background: In GBM the highest malignant brain tumor with a median survival of about 15 months dysregulated signalling of platelet derived growth factor receptors (PDGF-Rs) is implicated in pathogenesis. I/HU showed impressive efficacy and tolerability in patients (pts) with recurrent progressing GBM. In 30 pilot pts with recurrent GBM the progression free survival (PFS) at 6 and 24 months (m) was 32% and 16% respectively. Disease stabilisation (SD) in 37% was an important result. SD for more than 2 years was possible. In GBM a short period of SD after primary or relapse treatment is typical. In this phase II study the efficacy of I/HU as maintenance treatment in pts with GBM in stage of SD was analysed. Methods: From December 2003 up to June 2005 30 GBM pts with documented SD for more than 6 weeks following prior treatment, including surgery, radiotherapy and at least one chemotherapeutic regimen were included,. No enzyme-inducing anticonvulsive drugs were allowed. I dose was 600 mg od, HU dose was 1000 mg (500 mg bid) as continuous oral treatment, pts were followed up by blood cell count weekly and magnetic resonance imaging every 6 weeks. Results: All 30 pts were eligible for safety and for 6, 12 and 18 m PFS and overall survival (OS); 25 pts were male, 5 pts female, median age was 44 years (32 to 71), 24 pts had primary (de novo) and 6 pts secondary GBM. All 30 pts had prior radiotherapy, 21 pts had prior temozolomide and 9 pts non- temozolomide containing regimens. 8 pts were free from relapse, 17 pts after first and 5 pts after second relapse. The median observation time is 28 m. 6, 12 and 18 m PFS was 60% (18/30), 40% (12/30) and 30% (9/30) respectively. 6, 12 and 18 m OS is 90% (27/30), 67% (20/30) and 53% (16/30) so far. PFS for more than 24 m occurred in 3/6 pts with secondary and in 2/24 pts with primary GBM. Toxicity was low (anemia grade 3: 2 pt; grade 2: 4 pts; leucocytopenia grade 3:2 pts; grade 2: 7 pts; thrombocytopenia grade 2: 4 pts), HU dose was reduced in 8 pts, I dose in 1 pt and G-CSF was given in 8 pts, no treatment related death occurred. Conclusion: I (600 mg/d)/ HU (1000 mg/d) was well tolerated in this study. Long-term disease stabilisation was possible - especially in pts with secondary GBM. Confirmation in further investigation is required. [Table: see text]
A phase II trial of thalidomide (Thal) and procarbazine (Pro) in adults with recurrent or progressive malignant gliomas (MG)
Authors: Lesser G. J. , Stieber V. , Case D. , Enevold G. , Rosdhal R. , Tatter S. , Ellis T. , McMullen K. , Shaw E. 
Published: March 2020

2067 Background: Thal and Pro are among the few agents with demonstrated activity against MG. A two-stage, phase II trial was initiated within the WFURB to establish the response rate of combination Thal-Pro in patients (pts) with recurrent or progressive MG. Methods: Eligibility included pt age = 18 with measurable tumor on contrast enhanced brain scans; KPS = 60; normal liver, kidney and hematologic function; and treatment with = 2 prior regimens. Pts were required to participate in the S.T.E.P.S. Program and mandated to comply with agreed upon measures to avoid conception. Protocol therapy included Pro 250mg/m2/d x 5d q 28days and Thal 200mg/day continuously. Intrapatient dose escalation of Thal was attempted (increase by 100mg/day weekly as tolerated) to a maximum of 800mg/day. All pts received daily pyridoxine(100mg), warfarin(1mg) and stool softeners/laxatives. MRI/CT scans were performed prior to each odd cycle (every 8 weeks) to assess response based upon changes in the products of the largest bidimensional tumor diameters. Quality of life questionnaires including the FACT-Br were performed at baseline and prior to each odd cycle in all treated pts. Results: 18 pts (11 male) were enrolled (median age 50, range 27–63). One pt refused any therapy and is excluded from the analysis. The 17 treated pts received 36 cycles (median 2) of therapy. The median maximum Thal dose achieved was 400mg (range 200–800). No complete or partial responses were seen; 1 pt (6%) experienced stable disease, 14 (82%) progressed as best response and 2 (12%) were not evaluable for response. Median time to progression was 2.1 months (95% CI, 1.5–2.5). 14 pts have died; median survival was 7.6 months (95% CI, 3.5–9.4). Grade 3/4 drug related toxicity was minimal. Conclusions: Despite modest individual response rates in multiple prior phase II and III trials, the combination of Pro and Thal demonstrated no efficacy in this trial and this combination is unworthy of further investigation in pts with MG. Supported by NCI 1 U10 CA81851 and Celgene. No significant financial relationships to disclose.
Clinical outcome of glioblastoma multiforme patients with long-term survival
Authors: Yoon H. , Hottinger A. F. , DeAngelis L. M. , Lassman A. B. , Abrey L. E. 
Published: March 2020

2069 Background: Glioblastoma multiforme (GBM) patients generally have a dismal prognosis with average survival of one year. Long-term survival of 3 years or more is rare and the clinical outcome of these patients has been poorly studied. Methods: Retrospective review of patients surviving 3 years or longer following diagnosis of GBM at our institution between 1985 and 2003. Clinical characteristics and long-term outcome were reviewed. Pathology was confirmed at our institution for all patients. Results: 39 long-term survivors of GBM were identified. Median age at diagnosis was 47 years (range: 14 - 69 years). Fifteen patients (pts) were older than 55 at time of diagnosis, and 5 were over 60. Presenting symptoms were headaches (56%), seizures (28%), hemiparesis (12%), aphasia (17%) or confusion (5%). Median KPS at diagnosis was 90 (range: 50–100). One patient (4%) underwent biopsy and X patients each (48%) underwent complete resection and incomplete resections. All patients received focal radiation therapy (RT) with a median dose of 5940 cGy (range: 4500 - 6120 cGy); 7 received concurrent temozolomide. Adjuvant chemotherapy in 35 pts consisted of temozolomide (54%), BCNU (38%), intra-arterial cisplatin (4%), or PCV (4%). Estimated median survival was 6.16 years (range: 3.1 - 18.2). After initial treatment, 11 pts had continuous clinical and radiographic remission, 28 relapsed, and 12 died. Median KPS at last follow-up was 70 (range 40 - 100). However, 19 pts (49%) developed delayed treatment-related complications at a median of 2.7 years (range: 1 -12 years) from initial diagnosis. Six (15%) developed RT necrosis (none of whom received concurrent temozolomide), 12 (31%) developed a subcortical dementia with associated leukoencephalopathy, and 9 (23%) developed strokes thought to be related to prior treatment. Conclusions: Long-term GBM survivors remain rare but occur in all age groups. These patients have a high risk of developing clinically significant long-term complications of their treatment. No significant financial relationships to disclose.
Irinotecan and bevacizumab in progressive primary brain tumors: The Cleveland Clinic experience
Authors: Kang T. , Jin T. , Peereboom D. 
Published: March 2020

2077 Background: High-grade gliomas are generally resistant to modern chemotherapy. In the case of glioblastoma multiforme, median overall survival has been less than 12 months and progression free survival of less than 4 months. For patients with recurrent GBMs, the 6 month progression free survival is 15–20%. The combination of irinotecan and bevacizumab is an active regimen in the treatment of this disease. Herein we report the experiences with this regimen at our institution with the objective of identifying a therapy with a better outcome than historical results. Methods: Single institutional, retrospective review of 27 patients with recurrent or progressive high grade gliomas treated at the Cleveland Clinic Brain Tumor Institute from 7/2005 through 10/2006. Patients had progressed on at least one prior chemotherapy. Patients with prior irinotecan or bevacizumab were excluded. Patients were analyzed on an intention-to-treat basis, and outcomes estimated by the Kaplan-Meier method. Results: The median age of the group was 46 years (range 5–69). The median number of prior therapies was 2 (range 1–10). Twenty of 27 patients have progressed (74%), and 11 of 27 patients have died (41%). Kaplan-Meier estimates for outcomes are summarized in the table . Progression-free survival at 6 months is 46 %, with median of 5.1 months. Overall survival at 6 months is 84%, with median of 12.6 months. In 7 patients, treatment was terminated early prior to progression. Significant toxicities include: one patient who developed hematuria, one patient with deep venous thrombosis and one patient who experienced intracranial hemorrhage. Conclusions: Our experience suggests that the combination of irinotecan and bevacizumab improves the 6-month progression-free survival when compared to historical figures. The rate of severe toxicities is consistent with prior reports and mandates careful selection of patients. Further randomized, phase 3 studies should be done to validate these results. [Table: see text] No significant financial relationships to disclose.