bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase III randomized multicenter trial of surgical resection, BCNU-impregnated wafers, and irradiation versus surgical resection and irradiation alone for treatment of operable, solitary brain metastasis from systemic cancer
Authors: Newton H. B. , Volpi C. , Burkart J. , Miner M. E. , Gahbauer R. , Pearl D. K. , Ryken T. , Albright R. E. , Quigley M. 
Published: March 2020

11513 Background: Metastatic brain tumors (MBT) are the most frequent complication of systemic cancer. With conventional radiotherapy, survival remains poor, ranging from 24 to 32 weeks. Recent randomized trials suggest that surgical resection and irradiation of solitary MBT can extend survival and improve neurological quality of life. However, the role of chemotherapy remains unclear. A phase I/II trial demonstrated that interstitial chemotherapy with BCNU-impregnated wafers was well tolerated in this cohort, with an extended median survival and infrequent local recurrences. Methods: A randomized, multicenter phase III trial was begun to evaluate the ability of BCNU-impregnated wafers to improve survival and local time to progression in comparison to surgical resection and irradiation alone, with an expected accrual of 170 patients. Eligible patients were adults with systemic cancer of the lung or breast, with a solitary, accessible MBT that did not cross the midline or violate the ventricular system. Results: A total of 22 patients (female - 14; 20 with lung cancer), median age 60 years (range 39–77), were enrolled and randomized before the study was closed due to slow accrual. Each patient had undergone maximal surgical resection of the MBT and radiation therapy (35 Gy); wafers were placed in 12 patients (range 2–8 wafers). The median overall survival for the wafer and non-wafer groups were 35.0 and 47.4 weeks, respectively (log rank test, p = 0.54), with a 6-month survival rate of 67% and 56%, respectively (Fishers exact test, p = 0.67). Wafer placement was well tolerated. Conclusions: In this small cohort limited by slow accrual, the use of BCNU-impregnated wafers did not improve survival over surgical resection and irradiation alone. The wafers were well tolerated and did not adversely impact on quality of life. Although animal studies and phase I/II data are suggestive of activity, a large, multicenter, phase III comparative trial will be necessary to determine the efficacy of BCNU-impregnated wafers in patients with solitary, resectable MBT. [Table: see text]
Identification of prognostic factors in patients with brain metastases: A review of 493 patients
Authors: Baltalarli B. P. , Yalman D. , Akagündüz O. , Ozsaran Z. , Anacak Y. , Ozkok S. , Esassolak M. , Aras A. , Haydaroglu A. 
Published: March 2020

11516 Background: Choice of treatment for an individual patient with brain metastases is based on a number of factors: number and localization of brain metastases, systemic tumor activity, performance score, and age are major determinants for selection of treatment modality. Future trials in patients with brain metastases depend on selection of patients with favorable prognosis to allow adequate long-term follow-up to draw conclusions about survival and late toxicity, further stressing the importance of prognostic parameters. Our aim is to report the outcome of patients with brain metastases from solid tumors treated with whole brain radiotherapy (WBRT) in a single institution and identify the prognostic subgroups who will benefit from treatment. Methods: The records of 493 patients with brain metastases who had been admitted for WBRT in the Department of Radiation Oncology in Ege University Hospital between January 1997 and December 2002 was retrospectively evaluated. WBRT at this institution comprised of parallel opposed lateral fields, dosed to the midplane in a cobalt 60 teletherapy device. Radiotherapy fractionation were 10 fr. × 3 Gy, 5 fr × 4 Gy and 2 fr. × 8 Gy. Survival was calculated using the Kaplan-Meier method. Cox regression modeling was used for multivariate analysis and prognostical factors were determined on the basis of log rank test (SPSS 10.00 version). Results: Clinical response evaluation revealed that 254 patients (51%) had response to tretament whereas 104 patients (21.1%) had stable response and the other 43 patients (8.7%) had progressive disease.The median survival was 3 months (1–62 months) and 6 months survival was 41% and one year survival was 19%. Univariate analysis revealed that prognostical factors for survival were younger age (age <57) (p=0.043), female gender (p=0.019) and operation (p=0.0004), and for multivariant analysis female gender (p=0.027) and operation were determined (p=0.000). Conclusion: The prognosticators for survival in this retrospective analysis for patients with brain metastases are age, gender and operation. These factors affecting survival must be taken into consideration when the therapeutic management is to be made. And they may allow better selection of individual treatments. No significant financial relationships to disclose.
Remarkable response of adult-onset ganglioneuroblastoma in the advanced stage to unrelated cord blood transplantation: Case report
Authors: Takahashi T. , Morii T. , Amano I. , Tanaka H. , Tojo T. , Taniguchi S. , Kimura H. 
Published: March 2020

11524 Background: Adult-onset ganglioneuroblastoma (GNB) is a rare disease that carries the gravest prognosis. In this case report, we discuss a case of adult-onset GNB in the advanced stage which has responded favorably to unrelated cord blood transplantation (UCBT). Methods: The patient was a 22-year-old male. Posterior mediastinal tumor was excised and a diagnosis of GNB was made. The severity of GNB was classified as stage IV because bone metastasis affected the entire body. Three courses of combination chemotherapy using cisplatin (CDDP), cyclophosphamide (CY), vincristine sulfate (VCR) and pirarubicin hydrochloride-adriamycin (THP-ADR) turned out to be ineffective. Local radiation therapy to control the tumor metastasis to the right great wing of the sphenoid bone resulted in augmentation of the tumorous lesion. Then, bone marrow destructive pretreatment consisting of anticancer therapy [etoposide (VP-16) and thiotepa] and total body irradiation (TBI, 12Gy) was followed by UCBT. Cyclosporin and mycophenolate mofetil were administered to prevent graft versus host disease (GVHD). Results: The blood type compatible two-loci HLA mismatch transplant had 3.2x107 nucleated cells/kg. After the cord blood transplantation, the patient suffered complications such as acute GVHD (grade III), veno-occlusive disease (VOD) and viral hemorrhagic cystitis. Neuron-specific enolase (NSE), a GNB tumor marker, gradually decreased from 220 ng/ml to the normal level. The bone metastatic tumors were reduced in a stepwise manner. Fluorodeoxyglucose-positron-emission tomography (FDG-PET) scan demonstrated complete disappearance of abnormal accumulation. Three hundred days have passed since the unrelated cord blood transplantation. The patient is surviving and in the disease-free state. Conclusion: The remarkable response of adult-onset GNB in the advanced stage to UCBT has demonstrated the definite graft versus tumor (GVT) effect of UCBT on GNB. UCBT is regarded as a promising therapeutic intervention in solid tumors that are not associated with blood disorder. No significant financial relationships to disclose.
Chemoradiotherapy in multicentric glioblastoma multiforme—A clinical study
Authors: Papaiah Susheela S. , Bahl A. , R P. , Sharma D. , Julka P. , Rath G. 
Published: March 2020

11525 Background: Glioblastoma multiforme constitutes 40% of primary brain tumors. Multicentric Glioblastoma multiforme is rare about 3%.No definite guidelines is available in literature for management of these tumors. Methods: All Multicentric Glioblastoma multiforme were analyzed retrospectively from Jan 2003 to July 2005 for clinical behavior and response to chemoradiotharpy. Either Temozolamide or Carboplatin or Paclitaxel is used concurrently with radiation. Radiation dose 60 Gy/30 fractions over 6 weeks by bilateral parallel opposed fields was delivered using Cobalt-60 machine. Results: 27 cases were found, Male: Female 24:3, KPS 60 [40–70], Majority of them are symptomatic for 4 months, main symptoms were seizures, headache, vomiting, neurological deficite. 89% of them underwent one form of other surgical intervention. 11% were diagnosed on basis of radiological findings. 85% were supratentorial, 15% were both supra and infratentorial, one of which had spinal cord lesion. 6 [22%] patients did not receive any treatment. Among 21 patients 4 were treated only with radiotherapy, 17 with concurrent Chemoradiotherapy [Paclitaxel-8, Temozolamide-7 and Carboplatin-2]. 5 patients did not complete treatment. Among 16 patients only 6 came for first follow up, 5 of were concurrent Chemoradiotherapy [Temozolamide-4, Paclitaxel-l and RT alone 1]. At the end of 3 months only 2 patients with Temozolamide were alive. Conclusions: Multicentric Glioblastoma multiforme is an aggressive disease. Concurrent Chemoradiotherapy with Temozolamide has better role. No significant financial relationships to disclose.
Combined focal radiotherapy (FRT) and temozolomide (TEM) in the management of high grade malignant gliomas (HGMG): Romanian single centre experience
Authors: Bujor L. , Oprea C. , Pop M. , Perin R. , Vasile C. 
Published: March 2020

11526 Background: Standard treatment of HGMG is surgical resection followed by adjuvant FRT; chemotherapy is under investgation in postoperative setting combined with external FRT. The phase III study of Stupp et al favours the combined TEM and FRT for newly diagnosed HGMG with encouraging results in terms of both survival and disease free survival. We present the experience achieved in our centre with 18 consecutive patients with HGMG treated with FRT and TEM either concomitant or sequential. Methods: In the period January 2004–January 2006 eighteen consecutive adult patients age range 25–72 years, median 55 years, sex ratio M/F 10/8 with histologically proven HGMG have been refferd in our centre for adjuvant treatment. Most of the patients had deep situated tumors that precluded complete resection which has been performed in 6 out of 18 patients. For the remaining patients stereotaxic biopsy was the procedure of diagnosis. A maximum dose of 60 Gy FRT was delivered with dual energy photon (6–15 MV) linear accelerator over six weeks in 30 sessions. TEM was administered concomitant in continuous low daily doses 75 mg/sqm in five patients (all males) followed by maintenance 150–200 mg/sqm for up to six cycles. For three patients TEM was co-administered for two cycles of 200 mg/sqm during the days 1–5 and 29–33 of radiotherapy course and whereas for the remaining patients the TEM was given sequentially after the completion of FRT up to six cycles in 5/28 days schedule. Results: With a median follow-up of 11.5 months the overall survival was 9.7 months and the survival rate of 78.5%. Clinical examination was performed every week during FRT with neurological improvement and a decrease in the need of anticonvulsivants in all patients. According to CTC criteria no grade 3 and 4 grade toxicities were recorded. After the completion of FRT imaging evaluation (CT/MRI) was performed at 6 weeks time period with tumor regression in 75% of the patients and early recurrence in only 2 cases. Conclusions: Concomitant FRT and TEM is a safe and promising treatment in newly diagnosed cases of HGMG. Our preliminary experience confirms the data from literature and we will present updated results by the ASCO meeting time. No significant financial relationships to disclose.
Phase I dose and schedule finding study of pegylated liposomal doxorubicin (D) and weekly docetaxel (T)
Authors: Shaye O. S. , El-Khoueiry A. B. , Garcia A. , Wei D. , Groshen S. , Cole S. E. , Gitlitz B. J. , Chung C. T. , Lenz H. J. , Iqbal S. 
Published: March 2020

12012 Background: The combination of D and T has many potential applications, particularly in breast and ovarian cancers. A phase 3 trial is examining D + T versus T in first-line metastatic breast cancer ( NCT00091442 ). D has better tumor localization and penetration in solid tumors than conventional doxorubicin. In previous studies, the maximum tolerated dose (MTD) of the combination was identified as D 30 mg/m2 and T 75 mg/m2 q4 weeks (wks), with a recommended dose and schedule of D 30 mg/m2 and T 60 mg/m2 q3wks without G-CSF. We conducted a phase I study to determine the MTD of D with weekly T. Our hypothesis was that the lower incidence of myelosuppression with weekly T would allow for higher doses of both drugs. Methods: There were 2 schedules. Arm A: D q4wks starting at 25 mg/m2 with weekly T for 3 wks starting at 30 mg/m2. Arm B: D q2wks starting at 15 mg/m2 with weekly T for 3 wks starting at 30 mg/m2. One cycle was 28 days. Standard 3+3 design was used with MTD defined as the highest dose level causing dose limiting toxicity (DLT) in ≥ 2/6 patients (pts). Results: 32 pts were treated; 13 females, 19 males, median age of 60 years. Median number of cycles administered was 2 (1–13) with a median follow-up of 11.5 months. Tumor types included lung (16%), thyroid (9%), esophagus (9%), nasopharynx, breast, colorectal, stomach and kidney (6% each). Arm A (13 pts) was closed after 2/7 evaluable pts at dose level 2 (D 33mg/m2; T 30 mg/m2) experienced DLT in the form of grade 3 stomatitis. The most common grade 3/4 toxicities were neutropenia (3/13), stomatitis (3/13) and fatigue (3/13). Arm B accrued 19 pts. The trial was closed at the highest planned dose in Arm B (D 20mg/m2 q2wks and T 35 mg/m2 weekly) with only 1/6 evaluable pts experiencing DLT in the form of grade 4 fatigue and weakness. The most common grade 3/4 toxicities in Arm B included neutropenia (5/19 pts), fatigue (5/19 pts) and stomatitis (2/19 pts). There was no grade 3/4 hand-foot syndrome or cardiotoxicity. 2 partial responses were observed in nasopharyngeal and salivary gland carcinomas, with 13 pts achieving stable disease. Conclusions: The combination of D q2 wks and T weekly for 3/4 wks is well tolerated and results in a higher dose intensity of both drugs than in previously evaluated regimens. [Table: see text]
A phase I clinical study of biweekly carboplatin and gemcitabine in patients with advanced solid tumors
Authors: Kumar P. , Keshtgarpour M. , Kumar H. , Dudek A. 
Published: March 2020

12024 Background: Carboplatin (CBDCA) and gemcitabine (GEM) in combination is used commonly in lung cancer and is administered on a 21 day cycle. The purpose of this study was to determine the maximum tolerated dose (MTD) of CBDCA and GEM administered on a biweekly schedule and to assess safety and efficacy of this schedule. Methods: GEM was given intravenously (IV) over 30 minutes followed by CBDCA also given IV over 30 minutes. This combination was given on day 1 every 2 weeks. The dose levels examined are shown in the Table . A total of 26 patients were studied (18 male, 8 female) with median age of 56 (range 41–83 years); ECOG performance status of 24 patients were 0 (5), 1 (16), 2 (2), 3 (1); prior chemotherapy ranged from 0 to 4 regimens; median number of cycles administered per patient was 3 (range 1–9) with a total of 81 cycles. The primary tumors were lung (11), melanoma (4), head and neck (3), squamous cell penile/toe (2), bladder (2), kidney (1), gastric (1), esophageal (1) and ovary (1). Results: No DLTs were seen in any of these patients and the MTD was not reached. Delay in treatment was seen in total of 6 cycles due to myelosuppression and 1 cycle due to nausea and anorexia. Grade 3/4 hematological toxicity rates: anemia - 3/81 cycles (3.7%), neutropenia - 20/81 cycles (25%), and thrombocytopenia - 4/81 cycles (5%). Non-hematological toxicity was mild. The median time to progression was 40 days (range 4–133) and of 18 evaluable patients partial response or stable disease was seen in 7 (38.8%). Conclusions: Even at maximum tested dose of GEM at 2000 mg/m2 and CBDCA at AUC of 3.0, this schedule is well tolerated. Hematological toxicity such as neutropenia and thrombocytopenia was minimal. We plan to study this schedule of GEM and CBDCA in appropriate tumor types in combination with biologic agents. [Table: see text] [Table: see text]
Ex vivo generation and expansion of autologous anti-tumor CTL lines for adoptive cell therapy in patients with solid tumors
Authors: Pedrazzoli P. , Tunin I. , Tullio C. , Montini E. , Schiavo R. , La Grotteria M. , Locatelli F. , Maccario R. , Siena S. , Montagna D. 
Published: March 2020

12516 Background: Ex-vivo generation of cytotoxic T cell (CTL) lines able to selectively kill autologous tumor cells (TC) is crucial for adoptive cell therapy of cancer. We have described the ex vivo generation of anti-tumor HLA-restricted CTL using CD8-enriched blood mononuclear cells (PBMC) and dendritic cells, pulsed with apoptotic TC as source of tumor antigens (Montagna, Int J Cancer 2004). These cells possess a marked cytotoxicity against TC but very low levels of cytotoxicity against autologous non-malignant controls, suggesting their safe in vivo use. Aim of this study was to evaluate the possibility of generating a large number of anti-tumor CTL lines, in compliance with good manufacture procedure (GMP), to be utilized for adoptive cell therapy. Methods: Four patients with advanced, pretreated solid tumors have been evaluated: 2 sarcoma, 1 renal carcinoma and 1 ovarian carcinoma. Tumor sample was obtained during surgical procedures planned for therapeutic purposes, while PBMC were obtained by a single apheresis. All reagents employed for cultures were produced under GMP. Based on our reported method, the current protocol included two or three rounds of tumor-specific stimulation, followed by two rounds of antigen-independent expansion. Results: We have obtained, after the first round of expansion and in total, a range of 0.5–2×109 and 5–20×109 CTL, respectively. Such large amounts of anti-tumor CTL were generated even if a low number of viable TC was available. In 3 out of 4 anti-tumor CTL lines, >85% of effector cells were CD3+/CD8+. Conclusions: We demonstrated the feasibility of obtaining, in GMP conditions, large quantities of anti-tumor specific CTL suitable for in vivo use. A phase I protocol of lymphoablative therapy followed by CTL transfer in vivo has been designed and submitted for approval to the competent regulatory agency. No significant financial relationships to disclose.
Safety and pharmacokinetics (PK) of AMG 706, panitumumab, and gemcitabine/cisplatin (GC) for the treatment of advanced solid malignancies
Authors: Crawford J. , Burris III H. A. , Stein M. , Stephenson J. , Gilbert J. , Underwood S. , Sun Y. , Yang L. , Wiezorek J. , Schwartzberg L. S. 
Published: March 2020

13005 Background: AMG 706 is an investigational, oral, multi-kinase inhibitor with both antiangiogenic and direct antitumor activity targeting vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and Kit receptors. Panitumumab is a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFr) and has shown efficacy and tolerability in pts with solid tumors. The primary objectives of the first part of this multicenter, 2-part, dose-finding study were to establish the safety and tolerability of AMG 706 + panitumumab with GC. Secondary objectives included PK of all agents. Methods: Pts were sequentially enrolled in 1 of 5 AMG 706 dose cohorts: no AMG 706, 50 mg, 75 mg, 100 mg, and 125 mg QD; all pts received panitumumab (9 mg/kg i.v. on day 1), G (1250 mg/m2 i.v. on days 1 and 8), and C (75 mg/m2 i.v. on day 1) Q3W. Pts had advanced cancer for which GC is indicated, ECOG of 0 or 1, no symptomatic or untreated CNS metastases, no history of venous thrombosis, and no more than 1 prior chemotherapy regimen for advanced disease. Results: As of 8/05, 15 pts were enrolled (n = 7, no AMG 706; n = 8, AMG 706 50 mg QD). Baseline characteristics included 8M/7F, median (range) age of 61 (32, 72) years, 9 with ECOG 0 and 6 with ECOG 1. Tumor types included: non-small cell lung (8), pancreatic (3), esophageal (2), ovarian (1), and unknown (1). Safety for all 15 pts is presented (see table ). The PK of AMG 706 at 50 mg when coadministered with panitumumab/GC was similar to the PK for AMG 706 monotherapy at the same dose. Conclusions: These data suggest that AMG 706 can be safely combined with panitumumab and GC with no effect on the PK of AMG 706 at 50 mg QD. Updated safety and PK data will be presented. [Table: see text] [Table: see text]
Evaluation of platinum-based chemotherapy, glutathione metabolic genes, and survival in advanced non small cell lung cancer: A NCCTG 97–24–51 based study
Authors: Yang P. , Mandrekar S. J. , Hillman S. L. , Allen K. L. , Sun Z. , Wampfler J. , Cunningham J. M. , Jett J. R. , Adjei A. A. , Perez E. A. 
Published: March 2020

13013 Background: The glutathione metabolic pathway is directly involved in the inactivation of platinum compounds. Our earlier work indicated that genotypes corresponding to varied glutathione-related enzyme activities may predict survival in patients with advanced lung cancer. Herein, we evaluated the role of glutathione-related genotypes on clinical outcomes in stage IIIB/IV non-small cell lung cancer patients who were stable or responding from one prior platinum-based chemotherapy. Methods: DNA samples from patients who had tumor regression or stable disease after treatment with one platinum based chemotherapy regimen were analyzed using 6 polymorphic DNA markers that encode 5 important enzymes in the glutathione metabolic pathway. The contrasting genotypes used in the analysis were GCLC (homozygous repeat 77 vs. heterozygous 7*), GPX1 (CC vs. other), GSTP1-I105V (AA vs. other), GSTP1-A114V (CC vs. other), GSTM1 (null vs. present), and GSTT1 (null vs. present). Multivariable Cox proportional hazards models adjusted for age, gender, treatment arm, ECOG performance status, stage, and prior tumor response, were used to evaluate the prognostic significance of the genotypes at each locus. Results: Data from 112 patients with a median follow-up of 10.6 (range: 0.4–56.3) months was used. No significant difference in time to disease progression was observed for any of the genotypes. Among the 6 genomic DNA markers, the GCLC genotype was an important prognostic factor for overall survival after adjusting for other factors. In particular, patients carrying a 77 repeat genotype (homozygous) had a significantly worse survival (Hazard ratio = 1.67, 95% CI: 1.05–2.63). Conclusions: Genotypes of glutathione-related enzymes, especially GCLC, may be used as host factors in predicting patients’ prognosis after platinum-based chemotherapy. Further investigation to define and measure the effects of these genes in chemotherapeutic regimens is needed. (This work was partly supported by NIH research grants CA77118, CA80127, and CA84354.) No significant financial relationships to disclose.