bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synovial sarcoma: Retrospective analysis of treatment outcome and prognostic factors
Authors: Memon M. A. , Allam A. A. , El-Enbaby A. M. , El-Sebaie M. , Khafaga Y. M. , Schultz H. , El-Weshi A. 
Published: March 2020

20517 Introduction and Objectives: Synovial Sarcoma (SS) account for approximately 10 % of soft tissue sarcoma. Despite numerous case reports and several relatively large series, debate still exists about the prognostic factors for this disease, the biologic behavior and role of adjuvant chemotherapy. The purpose of this study is to analyze the variable prognostic factors that may affect the treatment outcome in patients with SS. Patient and Methods: Sixty-six patients with SS (36 males and 30 females) were seen in institution between January 1985 and December 2000. Median age at diagnosis was 29 years. Site of involvement include, lower extremities 43/66 cases; (65%), upper extremity 16/66 (24%), trunk 3/66 (5%), others 4/66 (include larynx, thyroid, neck, and hypopharynx).Tumor size: = 10 cm 42/66 (64%), = 10 cm 24/66 (36%). Patients with stage III and IV disease represented 58% of all patients (38/66), stage I and II 42%(28/66). All patients underwent surgery and adequate resection margins(= 2 cm) were achieved in 52% of cases. Histopathology: Biphasic 36/66, Monophasic 16/66, spindle cell 12/66 and not otherwise specified 2/66. Radiation therapy was given 44/66 cases (67%). Chemotherapy was delivered to 11/66 patients (17%). Results: With a median follow up of 50 months, the 5-year overall survival (OS) for all patients was 45%, while the 5- year relapse free survival (RFS) for patients treated with radical intent was 32%. Prognostic factors that significantly affected OS on univariate analysis were tumor size (≤ 10 cm vs > 10cm), tumor stage (stages I and II vs stage III), adequacy of surgical resection and local control. On multivariate analysis, tumor size and local control were the only independent factors that did affect OS. For RFS, sex, tumor size, tumor grade, tumor stage, and adequacy of surgical resection were the prognostic factors of significance on univariate. Tumor stage and sex were the only independent prognostic factors of significance on multivariate analysis for RFS. Conclusion: Tumor size, stage, grade, and adequacy of surgical resection are the main prognostic factors affecting OS and RFS. These parameters can help to identify the high risk patient who may qualify for aggressive treatment. No significant financial relationships to disclose.
The utility of the MDASI-BT in assessing symptoms in patients with brain metastases
Authors: Armstrong T. S. , Mendoza T. , Gning I. , Smith M. L. , Gilbert M. R. , Weinberg J. , Cleeland C. 
Published: March 2020

2052 Background: Symptom occurrence has been shown to predict treatment course and survival in patients with solid tumors. The M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) was recently validated in patients with primary brain. This study evaluated the reliability and validity of the MDASI-BT as well as symptom severity and prevalence in patients with brain metastases. Methods: Patients diagnosed with systemic cancer with brain metastases participated in this cross-sectional study. Data collection included demographic and clinical factors, and the MDASI-BT (0–10 scale). The average for the 22 symptoms and 6 interference items scores the MDASI-BT was computed. Construct validity was assessed using confirmatory factor analysis, and known-group validity was evaluated by detecting group differences due to disease severity and performance status. For reliability, Cronbach’s alpha values were computed for each subscale. Results: A sample of 124 patients participated, of which 53.2% females. Participants were primarily white (79.8%) and married (78.2%), with a variety of solid tumor malignancies represented. Factor analysis revealed six underlying constructs including affective, cognitive, focal neurologic deficit, constitutional, gastrointestinal, and interference with life. This solution explained 68.4% of the variance, and satisfied Harman’s criteria for model fit. Known-group validity was established for the MDASI-BT using the Karnofsky performance status (KPS). Mean symptom scores were 1.2 and 2.6, and mean interference were 1.8 and 4.3, for patients with good (90–100) and poor KPS (80 and below) respectively (p<0.001). These subscales were also sensitive to opioid analgesic use with group differences of 1.5 and 2.2 (p<0.001). Cronbach’s alpha was 0.9 for each of the two subscales. Fatigue, sleep disturbance, drowsiness, distress, and dry mouth were the most severe symptoms. Conclusions: The MDASI-BT demonstrated validity and reliability in patients with brain metastases and can be used to identify symptom occurrence related to the tumor and therapies. No significant financial relationships to disclose.
Gemcitabine in heavily pretreated adult soft tissue sarcoma patients
Authors: Schoeler D. , Kunitz A. , Reichardt P. 
Published: March 2020

20524 Background: The number of effective cytotoxic agents in treatment of advanced soft tissue sarcoma (STS) is limited when patients have failed anthracyclin and ifosfamide therapy. There are inconsistent data in phase I / II studies and retrospective analyses evaluating the efficiacy of gemcitabine (G, 900mg/m2, d1+8, q3w) or combination of gemcitabine and docetaxel (GD, G: 900mg/m2, d1+8, D: 100 mg/m2, d8, q3w). Methods: Between 2002 and 2006 we retrospectively analyzed 14 females and 6 males with heavily pretreated advanced soft tissue sarcoma (1–5 pretreatments) who were treated in our department (Charité Campus Virchow-Klinikum) with G (n=10) or GD (n=10) depending on their performance status. The following histology types were represented: leiomyosarcoma (10), liposarcoma (3), MPNST (3), synovial sarcoma (2), undifferentiated sarcoma (1), malignant large cell sarcoma (1). Results: A total of 99 cycles (range 1 to 15) were applied. Best response was partial remission (PR=20%, G: n=2, GD: n=2) and was achieved in four patients, among them three leiomyosarcoma and one MPNST. In six cases disease stabilization was achieved for up to 15 month (SD=30%, G: n=2, GD: n=4). Four patients had progressive disease after 2–3 cycles of gemcitabine based therapy (PD=20%, G: n=0, GD: n=4). In another six cases only day one of the first cycle (G alone) was administered because of serious problems due to pretreatment and poor performance status (e.g. prolonged thrombopenia and neutropenia Grade IV, gemcitabine-induced vasculitis, gastrointestinal bleeding due to tumor localization, pneumonia, rapid tumor progression). Conclusions: Gemcitabine-based therapy for heavily pretreated STS patients in our retrospective analysis has a significant overall response rate. In patients considered unfit for GD combination, single agent G treatment remains an option with moderate effiacy. No significant financial relationships to disclose.
Treatment of adult rhabdomyosarcoma
Authors: Staddon A. P. , King J. J. , Ogilvie C. M. , Hartner L. , Fox E. J. , Lackman R. D. 
Published: March 2020

20526 Background: Adult rhabdomyosarcomas are rare tumors that are clinically aggressive with high rates of metastasis. This study aimed to determine short-term patient outcomes and responses to chemotherapy using doxorubicin, ifosfamide, and vincristine in the treatment of adult rhabdomyosarcomas. Methods: After IRB approval, 13 adult rhabdomyosarcoma patients (8 males, 5 females) were identified from 1998 until 2006. Of these patients, 6 had metastatic disease on presentation, 4 had neoadjuvant treatment, and 3 had adjuvant treatment. One patient with metastatic disease refused treatment. Twelve patients were treated with doxorubicin, ifosfamide, and vincristine initially with 2 patients also receiving cyclophosphamide and VP-16. The standard regimen was doxorubicin 25 mg/m2 D1- 3, ifosfamide 2.5 gm/m2 D1–4, and vincristine 1.4 mg/m2 D1,8 every 21 days. The majority of patients received 6 cycles of chemotherapy. Average age was 48 years (20 to 73 years). Seven had pleomorphic subtype, 3 alveolar, and 2 embryonal. The primary tumor was in the upper extremity in 4 patients, lower extremity in 5, chest wall in 2, and cervix in 1. Outcome measures were response to chemotherapy, disease status at last follow-up, and survival from the initiation of treatment. Results: Of the 5 treated patients with metastatic disease on presentation, 1 had a complete response (CR) and has no evidence of disease (NED) post-resection at 14 months. 1 had progression and is alive with metastasis at 5 months. 3 patients had a partial response (PR) with later progression and died of disease at 8, 14, and 24 months. Of the 4 patients treated neoadjuvantly, 3 are currently alive NED at 7, 10, and 10 months (2 had pathologic CR and 1 had PR) and 1 patient had a PR with later progression and died at 19 months. Of the 3 patients treated with adjuvant chemotherapy, all 3 are alive NED at 2, 17, and 37 months. Median overall survival was 12 months with 8/12 (67%) alive at last follow-up and 7/12 (58%) alive NED at a median of 10 months. Conclusions: Treatment of adult rhabdomyosarcoma using doxorubucin, ifosfamide, and vincristine shows significant activity with some pathologic CRs and a 58% disease-free survival rate at a median of 10 months. No significant financial relationships to disclose.
Does neo-adjuvant chemotherapy increase the risk of infection after limb salvage surgery for bone tumors?
Authors: Sankaranarayanan S. , Sokolovskiy V. , Voloshin V. , Aliev M. , Zubikov V. , Nisichenko D. , Sokolovskiy A. 
Published: March 2020

20532 Background: Neo-adjuvant chemotherapy is commonly used to eradicate the micro metastases and to prepare the patient for limb-salvage surgery. It helps the surgeon to get good oncological margin intraoperatively. Methods: Between the period of 1992 - 2005, 321 patients underwent limb salvage surgery for bone tumors at the Department of General Oncology (Bone & Soft tissue tumors), N. N. Blokhin Russian Cancer Research Center & Moscow Regional Clinical Research Institute, Moscow, Russian Federation. 230/321 patients (Group A) received neo-adjuvant chemotherapy. The course of chemotherapy ranges from 2 to 11 cycles. 95/321 patients (Group B) did not receive neo-adjuvant chemotherapy. The histological diagnoses were: 155 - High grade osteosarcoma, 38 - Giant cell tumor, 36 - Malignant fibrous histiocytoma, 29 - Chondrosarcoma, 25 - Periosteal osteosarcoma, 21 - Metastasis from other organs and 17 - Ewing's tumor. Results: In Group A, 27 patients (11.7%) and in Group B, 7 (7.3%) had infection of endoprosthetic bed. Suppression of the immune system by chemotherapeutic agents is the main reason for the higher incidence of infection in Group A. All the 27 patients in Group A and 2 patients in Group B had revisional endoprosthetic replacement. In group A 7/27 and in Group B none of the 7 patients died of post operative infection. The follow-up ranged from 1 - 13 years (mean follow-up 6 years). Discussion: In our opinion, it has a major disadvantage, i.e. it increases the risk of postoperative infection. How best to combine this drug is still unknown. In the future, therapy for bone tumors should be enhanced by advances in pharmacology, immunology, and molecular genetics that will lead to more efficacious, specific and less toxic treatments. An interdisciplinary team approach is needed in order to advance the goal of local tumor control, limb salvage with optimum extremity function, minimal morbidity and improved long term survival. No significant financial relationships to disclose.
A case report of sarcoma regression in a patient with MDS treated with lenalidomide
Authors: Shammo J. M. , Kassar M. , Robin I. , Knight R. 
Published: March 2020

20535 Background: Lenalidomide is an immunomodulatory drug recently approved for the treatment of MDS patients with del 5q cytogenetic abnormality. Here we describe a case of sarcoma regression in a patient with MDS who had been treated with lenalidomide. Method: An 84 year old man was diagnosed with low risk MDS in November 2002, he was transfusion dependent requiring 2–4 units of blood a month. He was enrolled on the MDS 002 trial in February 2004. He became transfusion independent by cycle 4. Results: In March 2005 he developed abdominal pain and a CT of the abdomen revealed a 2 x 2 cm mass involving the lesser curvature of the stomach. An MRI of the abdomen followed, confirming the presence of an enhancing gastric lesion, a biopsy of the mass revealed low grade malignant sarcoma. The patient was a poor surgical candidate and the decision was made to follow the progression of the mass with repeat imaging. In October 2005 a repeat MRI failed to visualize the previously noted mass, a recent CT performed in December 2006 was also negative for the presence of the mass. A potential therapeutic role for lenalidomide in this case which may have led to the regression of the sarcoma is possible although spontaneous regression can not be ruled out. It is not known if the mass was present at the time of enrollment on the clinic trial, it is also not clear as to why the patient presented with abdominal pain several months into the clinical trial. There had been several case reports in the literature describing similar results with thalidomide in patients with soft tissue sarcoma however, to our knowledge this clinical observation has never been reported with lenalidomide previously. Conclusion: This observation merits consideration for prospectively evaluating the efficacy of lenalidomide in patients with sarcoma for whom limited therapeutic options currently exist. No significant financial relationships to disclose.
Phase I study of erlotinib and CCI-779 (temsirolimus) for patients with recurrent malignant gliomas (MG) (NABTC 04–02)
Authors: Robins H. I. , Wen P. Y. , Chang S. M. , Kuhn J. , Lamborn K. , Cloughesy T. , Glibert M. R. , Yung W. K. , Dancey J. , Prados M. D. 
Published: March 2020

2057 Background: Glioblastomas (GBM) frequently have amplification/mutation of EGFR and inactivation of PTEN. Although single agent EGFR and mTOR inhibitors have only modest activity, there is a rationale for combinations of these agents. Methods: The North American Brain Tumor Consortium (NABTC) is conducting a phase I/II study of the EGFR inhibitor erlotinib in combination with the mTOR inhibitor CCI-779 in recurrent MG. Eligibility criteria were histologically proven GBM and anaplastic gliomas (AG), radiologic progression, > 18 yrs old, KPS > 60, adequate bone marrow reserve and organ function. Patients (pts) must not be receiving enzyme inducing antiepileptic drugs. The dose of erlotinib was fixed at 150 mg/d. Patients initially received CCI-779 50 mg intravenously once weekly and the dose was adjusted based on toxicities. Dose-limiting toxicities (DLT), determined during the first 4 weeks of therapy, were defined as any grade (G) 4 hematologic toxicity except for G3 thrombocytopenia, and any G3 or unacceptable G2 non-hematologic toxicities. Escalation was performed in groups of 3. The maximum tolerated dose (MTD) was defined as the dose at which DLTs occurred in no more than 1/6 pts. Results: To date 22 eligible pts have been enrolled (15 GBM; 7 AG). Patient characteristics were 12 male, 10 female; median age: 54 (26–74); median KPS 90 (70–100); median prior chemotherapy regimens 1 (0–3). Two of 3 pts receiving 50 mg of CCI-779 developed DLTs (intolerable G2 rash & mucositis, & G3 liver function abnormalities; G3 rash & dehydration). Three of 6 pts receiving 25 mg of CCI-779 weekly experienced DLTs (G3 rash; G3 rash, diarrhea, dehydration; G3 mucositis & infection). Two of 6 patients receiving weekly 15 mg of CCI-779 experienced G3 rash. The protocol was amended to define a DLT only if > G3 toxicities persisted despite maximal therapy. Six additional pts were treated at 15 mg of CCI-779. One of 6 pts developed a G3 rash. Conclusions: The combination of erlotinib and CCI-779 was associated with a higher than expected incidence of rash and mucositis. The MTD for this combination is likely to be 150 mg/d of erlotinib and 15 mg/d of CCI-779. Final pharmacokinetics and response data will be presented. No significant financial relationships to disclose.
A phase I trial of sorafenib (BAY 43–9006) for patients with recurrent or progressive malignant glioma (NABTT 0401)
Authors: Nabors L. B. , Rosenfeld M. , Chamberlain M. , Phuphanich S. , Batchelor T. , Supko J. , Desideri S. , Xiaobu Y. , Wright J. , Grossman S. 
Published: March 2020

2058 Background: Sorafenib (BAY 43–9006) is a small molecule inhibitor of multiple kinases to include raf, VEGF receptors, and PDGF receptors. The molecule has demonstrated anti-proliferative and anti-angiogenic activity in a number of in vitro and in vivo model systems. Methods: In this multi-institutional trial, we have conducted a phase I dose-escalation study to determine the maximum tolerated dose (MTD) of sorafenib in patients with recurrent malignant glioma. Cohorts of 3 patients, stratified based on the use of enzyme inducing anticonvulsants (EIAC) or not (non-EIAC), have completed enrollment through the following dose levels: 200 mg, 400 mg, 600 mg, and 800 mg. Therapy has been given as a twice daily oral administration with cycles of 28 day duration. Results: A total of 35 patients have been enrolled and are evaluable for toxicity. Treatment related dose-limiting toxicity (DLT) was defined as any grade 3 or 4 non-hematological toxicity, and grade 4 hematological toxicity (platlets and ANC) or febrile neutropenia of any duration. The following DLTs were observed: one grade 3 hand-foot-syndrome at the 400 mg BID (EIAC), one grade 3 puritis 400 mg BID (non-EIAC) dose level, grade 3 hand/foot syndrome 800 mg BID (EIAC and non-EIAC arms), grade 3 hypophosphatemia 800 mg BID (EIAC), and grade 3 joint pain 800 mg BID (EIAC). A MTD of 600 mg BID has been defined for the EIAC arm with 3/6 DLTs at 800 mg BID. A MTD has not been defined and enrollment has been completed through the 800 mg BID dose level for the non-EIAC. Of the enrolled patients, 20 are with glioblastoma multiforme (GBM), 8 with anaplastic astrocytoma (AA), and 7 with anaplastic oligodendroglioma (AO). Conclusions: The MTD for sorafenib is 600 mg BID for patients on EIAC. Sorafenib is well tolerated with limited toxicities to doses of 800 mg twice daily in patients with recurrent malignant glioma not on EIAC (non-EIAC arm). No significant financial relationships to disclose.
A phase I trial using the proteasome inhibitor bortezomib and concurrent temazolomide and radiotherapy for high grade gliomas
Authors: Dicker A. , Werner-Wasik M. , Machtay M. , Mallon G. , Ramirez M. , Andrews D. , Curran W. J. 
Published: March 2020

2061 Background: Improving the response of patients with high-grade astrocytomas continues to remain a challenge despite advances in chemoradiation. Preclinical studies have demonstrated the importance of the NF-kappaB pathway treatment resistance and enhancement of radiosensitivity by proteasome inhibition. This open-label, phase I study evaluated the safety of 3 dose levels (0.7, 1.0, 1.3 mg/m2/dose) of intravenously administered bortezomib, a reversible proteasome inhibitor with unique properties in combination with chemoradiation. Methods: Eligible patients had a diagnosis of high-grade glioma. Other requirements included performance status 0–1 and adequate hematologic reserve. Previous radiotherapy and/or chemotherapy was allowed. Patients received fraction sizes of XRT that ranged from 1.8–3.5 Gy/day for total doses between 35–66 Gy. During radiotherapy, temozolomide was administered continuously at a daily dose of 75 mg/m2. The starting dose level of bortezomib was 0.7 mg/m2/ days 1, 4, 8, 11 of 21-day cycle for up to 2 cycles. This was followed by 1.0 mg/m2 and 1.3 mg/m2 dose levels. The primary endpoint of the study was dose-limiting toxicity (DLT), defined as any Grade 4–5 toxicity or Grade 3 toxicity(ies) requiring hospitalization and/or XRT interruption. Response was also assessed (1-month post-XRT brain MRI). Results: A total of 27 patients were enrolled. There were no DLTs observed in any dose groups. Grade 1 and 2 toxicities consisted of stomatitis, erythema, and alopecia. Of 24 patients evaluable for response, 1 patient had no evidence of disease, 3 patients had a PR; 9 patients had stable disease and 11 patients had progressive disease. Conclusions: Bortezomib can be combined at full dose with concurrent temozolomide and radiation therapy with minimal adverse effects. Correlative translational endpoints are still pending. The results observed justify further evaluation in a phase II setting. [Table: see text]
A phase I study of SDX-102 for the treatment of patients with MTAP-deficient recurrent malignant gliomas
Authors: Phuphanich S. , Chamberlain M. , Mikkelsen T. , Ye X. , Grossman S. A. , Batchelor T. , Lesser G. , Fisher J. D. , Desideri S. 
Published: March 2020

2063 Background: De novo purine biosynthesis entails two metabolic pathways of which one pathway is frequently impaired in cancer due to gene deletion of the rate limiting enzyme, methythioadenosine phosphorylase (MTAP). In MTAP-deficient cancers, SDX-102 inhibits purine biosynthesis by blocking the remaining synthetic pathway. This study was to determine the maximum tolerated dose (MTD), toxicity and pharmacokinetic activity of SDX-102 in the treatment of recurrent MTAP-deficient malignant gliomas. Methods: Eligible patients had recurrent supratentorial MTAP-deficient malignant gliomas treated previously with surgery, radiation and = 2 regimens of chemotherapy. Dose escalation was conducted separately for patients taking enzyme inducing anti-seizure drugs (EIASD+) and for those not (EIASD-). The starting dose in both groups was 80 mg/m2/day continuous infusion for 5 days every 3 weeks, cycle length was 3 weeks. Dose escalation was in a stepwise fashion in cohorts of three patients, up to a maximum dose of 125 mg/m2/day. Results: 118 patients were screened of which 39 (33%) had MTAP-deficient tumors. 21 patients (14 males/7 females) were enrolled between 9/17/04 and 3/17/06. Median age was 50 years (23–76); median KPS was 90 (60–100); 16 patients (76%) had GBM. Two dose levels of SDX-102 were tested in the EIASD+ group: 80 mg/m2/day (n=4) and 100 mg/m2/day (n=3), 3/3 dose limiting toxicity (DLT) were noted with grade 3 mucositis at 100 mg/m2/day , so in the EIASD+ group the MTD was 80 mg/m2/day. Three dose levels were tested in the EIASD- group: 80 mg/m2/day (n=4), 100 mg/m2/day (n=7), 1/3 patients had DLT (Grade 4 mucositis) at 100 mg/m2/day and the cohort was expanded for additional 3 patients without DLT noted; and 125 mg/m2/day (n=3) amongst whom no DLT was observed. No MTD was determined in the EIASD- group because the MTAP assay became unavailable through the sponsor. There were a range of 1–14 cycles administered in this patient population. Conclusions: SDX-102 infusion is safe and feasible in patients with recurrent MTAP-deficient malignant gliomas. The MTD in EIASD+ patients is 80 mg/m2/day. The EIASD-group MTD has not been determined however the highest dose tested is 125 mg/m2/day. No significant financial relationships to disclose.