bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2-positive breast cancer cells percentage and progression to trastuzumab treatment in metastatic patients
Authors: García-García Y. , Martínez-Fernández A. , Muñoz Mateu M. , Fernández-Ruiz P. , García-Albéniz X. , Mármol-Casas M. , Domingo-Doménech J. , Pineda-Losada E. , Visa-Turmo L. , Gascón Vilaplana P. 
Published: March 2020

11510 Background: Immunohistochemistry (IHC) assay for HER2 in breast cancer (BC) identify patients (pts) who are at benefit from Trastuzumab (T) therapy. The percentage (%) of positive cells is not known to have prognostic significance. Methods: We analyze pts that received T as a treatment for metastatic BC in our center, in monotherapy or in combination with other agents, and to ascertain whether the % of her-2 positive cells can be a predictive factor of response to therapy with T. We define HER-2 positive cells according to the Envision method 3+, valuating the percentage of cells with positive result. If the result of the IHC was 2+, we use fluorescence in situ hybridation (FISH). For a total of 36 patients treated, the results of the % were available only for 21 patients. The median of positive cells was 90% (range 30–100%) and it was taken to define low percentage of positive cell tumors (LPPCT) or high percentage of positive cells tumors (HPPCT). We evaluated the initial response (disease progression-stability versus parcial-complete response), the time to progression (TTP) and the overall survival (OS) of pts on T. We used the log-rank test to determinate the TTP and Fisher’s exact text to determinate the initial response and the OS on therapy with T. Results: TTP to T was significantly higher in LPPCT (median 19 months, CI 10–28) than in HPPCT (median 13 months, CI 7–19) (p=0.037). We didn’t find significant differences regarded to baseline characteristics of the patients, response nor OS. Conclusions: We find that the % of HER2-positive cells is significantly correlated with the TTP in patients on T therapy. The percentage of HER2-positive cells can be at clinical interest as a predictive factor of response to her-2 targeted therapy and it must be confirmed with a large number of pts. No significant financial relationships to disclose.
Bevacizumab, a monoclonal antibody to the vascular endothelial growth factor (VEGF), and irinotecan for treatment of recurrent primary malignant brain tumors in adults
Authors: Lassen U. , Grunnet K. , Kosteljanetz M. , Hasselbalch B. , Laursen H. , Poulsen H. S. 
Published: March 2020

12503 Background: The prognosis of recurrent malignant brain tumors is poor, and no efficacious therapy exists in patients previously treated with radiotherapy and standard chemotherapy. Bevacizumab (B) binds to VEGF and inhibits tumor angiogenesis, and treatment with this drug might induce tumor regression and prolongation of life. Irinotecan (I) is a topoisomerase 1 inhibitor with modest effect on recurrent primary brain tumors. The combination of B and I in recurrent malignant gliomas was presented at ASCO 2006 and showed very encouraging responses. Methods: We report confirmatory results of the combination of B and I in a consecutive series of patients with primary malignant brain tumors recurring after standard primary and secondary treatment (surgery, radiotherapy and standard or secondline chemotherapy).With standard inclusion criteria, including PS 0–2, patients received B as 10mg/kg, and I 125 mg/m2 in patients not treated with enzyme inducing antiepileptic drugs (EIAED) or 340 mg/m2 in patients treated with EIAED every other week until progression or non-manageable toxicity. Response evaluation was performed by MacDonald criteria and MRI scans. Results: The results of 31 patients is presented, 15 with grade IV tumors (Glioblastoma multiforme), 7 with grade III anaplastic astrocytomas, 5 with anaplastic oligodendrogliomas, 1 with anaplastic ependymoma, 1 with hemangiopericytoma, 1 with prolactinoma, and 1 with medulloblastoma. Four patients had complete response, 3 grade IV tumors and 1 anaplastic oligodendroglioma. One patient had partial response (> 50% tumor reduction), 12 had stable disease (3 had tumor reduction between 31 - 45 %). 14 progressed. No grade 4 toxicity was observed and most patients experienced grade 1–2 toxicity. Two tromboembolic events and 1 intestinal perforation were observed. Conclusion: The combination of B and I is safe, induces tumor regression in a substantial number of patients, and can be used as treatment to patients recurring after standard treatment. No significant financial relationships to disclose.
Temozolomide and irinotecan for relapsed glioma: Charing Cross Hospital experience
Authors: Young A. G. , Mulholland P. J. , Waldman A. D. , Roncaroli F. , O’Neill K. S. , Davidson S. J. , Glaser M. G. , Brock C. S. , Newlands E. S. 
Published: March 2020

12504 Background: Patients (pts) with relapsed glioma have poor prognosis with few treatment options. Methods: Retrospective analysis was made of toxicity and outcome in pts with relapsed glioma treated between 2001–06 with temozolomide (TMZ, 75mg/m2/day, D1–21) & irinotecan (IRINO, 125mg/m2, D1, 8, 15), q35. Toxicity was graded using NCI-CTC version 2.0. Progression free survival (PFS) was calculated from start of TMZ/IRINO to relapse. Results: 24 pts (M:F, 15:9) were treated, comprising glioblastoma multiforme (GBM) (n=11); anaplastic astrocytoma (AA) (n=7); astrocytoma (n=4); oligoastrocytoma (n=2). Primary treatment following biopsy (n=12) or debulking surgery (n=12) was radiotherapy (RT) alone (n=12) or in combination with TMZ (n=12) (Stupp et al, 2005). At relapse, 10/24 pts received TMZ/IRINO as second-line therapy following TMZ+RT. 12/24 pts received third-line TMZ/IRINO, after TMZ alone (n=9), or TMZ/procarbazine (PCB) (n=2) or IRINO alone (n=1). 2/24 pts received fourth-line TMZ/IRINO, after TMZ then IRINO (n=1) & after TMZ/PCB then IRINO (n=1). 19/21 pts took enzyme-inducing antiepileptic drugs (EIAED). EIAEDs can potentially reduce IRINO exposure. 218 chemotherapy cycles (median, 5; range 1–42+) were given. Grade (G) 3 or 4 hematological toxicities were leucopenia (G3, n=3, 1.4%), neutropenia (G3, n=3, 1.4%; G4, n=1, 0.5%), lymphopenia (G3, n=64, 29%). 5 pts (20.8%) had cotrimoxazole prophylaxis; 1 pt developed PCP on it. 1 pt developed G3 urogenital sepsis. There were no other G3 or G4 toxicities. 13 cycles were delayed due to G2 infection (5.9%). 3 pts had dose reductions.1 pt died from AML; in retrospect symptoms appear to pre-date treatment start. Overall median PFS was 6 months (mo) (range 1.5–39.75+ mo). Overall 2 yr PFS was 28% (95%CI: 10–47%). Median PFS was: GBM 2.5mo (range 1.5–27.25+ mo); AA 11.5 mo (range 2–33.5+ mo). Median 2yr PFS was: GBM 27% (95%CI: 1–53%); AA 14% (95%CI: 0–40%) Conclusions: TMZ/IRINO is well tolerated in heavily pre- treated pts & warrants further evaluation. Long PFS was seen in pts with relapsed GBM & AA. Importantly, re-challenge including TMZ can induce durable response. [Table: see text]
NT-3/TRK-C regulated proteins in the biology of medulloblastoma
Authors: Gruber-Olipitz M. , Strobel T. , Quehenberger F. , Grotzer M. A. , Lubec G. , Slavc I. 
Published: March 2020

12519 Background: Medulloblastoma (MB) is the most common malignant childhood brain tumor. Because of its high risk of leptomeningeal dissemination, standard postoperative treatment includes craniospinal irradiation and chemotherapy. Such treatment produces significant sequelae including neurocognitive dysfunction, endocrine and growth disturbances. These therapy-induced morbidities warrant a novel less toxic approach possibly targeting key molecules within specific pathways of medulloblastoma biology. Recent reports identified high neurotrophin receptor TrkC mRNA expression as a powerful independent predictor of a favorable survival outcome in MB patients. However, the role of activated TrkC receptors in the development and biology of MB remains unclear. Methods: To determine downstream effector proteins of TrkC signaling, the medulloblastoma cell line DAOY was stably transfected with a vector containing the full-length TrkC cDNA sequence or an empty vector control. Accounting for the complexity of ligand-induced changes in cellular pathways and effector proteins, we investigated proteomic changes at multiple time points for up to 48 hrs following neurotrophin-3 induced TrkC receptor activation. Results: We identified 18 proteins differentially expressed: Caldesmon; Cathepsin D; Metastasis inhibition factor nm23; Multidrug resistance-associated protein Mgr1-Ag; Vimentin; Vinculin; Superoxide dismutase (Mn); Glutathione S-transferase P; Stathmin, Lamin A/C, Valosin-containing protein, Annexin A1; ULIP protein; DJ-1 protein; Fascin; Mitofilin; Heterogeneous nuclear ribonucleoprotein H and K. Conclusion: The proteins affected play substantial roles in differentiation, migration, invasion, proliferation, apoptosis and drug resistance. Almost all of the proteins have been described as being essential in the pathogenesis of different solid tumors, but have not been related to MB pathogenesis so far. No significant financial relationships to disclose.
Comparison of chemotherapy regimens for malignant gliomas with positive MGMT protein expression: Experience of 51 cases
Authors: Zhang J. , WU Q. , Chen Z. 
Published: March 2020

12522 Background: To compare the efficacy and toxicity of three chemotherapy regimens for MGMT positive gliomas. Methods: Fifty-one patients with histologically confirmed malignant gliomas and MGMT positive expression were enrolled in this study. The glioma tissues were examined for MGMT protein expression by immunohistochemistry. The patients were treated with: 1, regimen contained of nitrosourea (nitrosourea group) 11 cases; 2, regimen contained of temozolomide (temozolomide group) 18 cases; regimen contained of neither nitrosourea nor temozolomide(no alkylating agent group) 22 cases. Response to chemotherapy was evaluated according WHO criteria, and toxicity was evaluated according National Cancer Institute (NCI) criteria. Results: The overall objective response rate (CR + PR) for 51 cases with MGMT position gliomas was 20%, and disease control rate (CR+PR+SD) was 59%. The objective response rate and disease control rate in nitrosourea group, temozolomide group, and no alkylating agent group were 0%,18.2%,16.7% and 61.1%,31.8%,77.3%, respectively. There was significant difference between no alkylating agent group and nitrosourea group (P<0.05). Hematological toxicity and nausea/vomiting were main side-effect observed in nitrosourea group. While there was comparative lower incidence of side-effect in temozolomide group. Hematological toxicity, nausea/vomiting, and alopecia were main side-effect observed in no alkylating agent group. Though there was higher incidence of 3–4 grade hematological toxicity in this group, but it could recovered by oneself in one week or through treatment with G-CSF for 3–5 days. Conclusions: Regimen contained no alkylating agent group can obtain higher response rate and thus is worth of recommending to patients with MGMT positive gliomas. However, since modest response rate and good toleration, regimen with temozolomide shouldn’t be given up in MGMT position gliomas. Nevertheless, It is necessary to discover more efficiency way of using temozolomide. Nitrosourea should not be recommended to MGMT position glioma patients. No significant financial relationships to disclose.
Adjuvant chemotherapy with temozolomide and radiation therapy in patients with high grade gliomas
Authors: Pedersini R. , Vattemi E. , Lusso M. , Baier S. , Campello M. , Broger M. , Schwarz A. , Maffei M. , Lukas P. , Graiff C. 
Published: March 2020

12534 Background: Temozolomide, a novel alkylating agent, has shown activity in the treatment of patients with high-grade gliomas. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant chemo- radiotherapy according to Stupp regimen. Methods: We reviewed our experience with a combination of radiotherapy (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). Results: 43 patients , median ECOG PS= 0, were treated with concomitant RT and Temozolomide at our institution since March 2004. Median age was 63 (range 33–73), with 62% over 60 years. All patients had histologically confirmed high grade gliomas: glioblastoma multiforme (32), grade III oligodendroglioma (3), grade III oligoastrocytoma (2), grade III astrocytoma (6). 2/43 patients underwent only a biopsy, the remaining underwent debulking surgery. At a median follow-up of 17 months, the median progression-free survival (PFS) was 6 mo and median overall survival (OS) was 12 mo. Median PFS and median OS were similar in elderly ( = 60 years). Treatment was well tolerated. Only one patient had grade IV haematological toxicity. One patient discontinued treatment due to hepatotoxicity. Conclusions: Our findings confirm the results of the EORTC trial(Stupp R et al., 2005) No significant financial relationships to disclose.
Phase I study of the antifolate pralatrexate given with vitamin B12 and folic acid supplementation in patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: Azzoli C. G. , Krug L. , Miller V. , Bekele S. , Tyson L. , Dunne M. , Huntington M. , Saunders M. , Kris M. G. 
Published: March 2020

13006 Background: Pralatrexate is a novel antifolate that has shown promising activity in the treatment of pts with previously- treated NSCLC at doses of 135–150 mg/m2 IV every other week (q2w). [Krug, Clin Cancer Res 9(6), 2003; 6(9), 2000] The addition of vitamin B12 and folic acid supplementation may mitigate toxicity from pralatrexate and improve efficacy by allowing higher doses to be delivered. Methods: This study is designed to determine the maximum tolerated dose (MTD) of pralatrexate in combination with vitamin B12 and folic acid supplementation in pts with NSCLC. Key eligibility criteria include confirmed stage IIIB or IV NSCLC; at least 1 prior chemotherapy regimen; Karnofsky performance status (KPS) = 70%; and no other active concurrent malignancy. Using a rapid escalation design, pralatrexate was initially administered at a dose of 150 mg/m2 IV q2w, escalating by 40 mg/m2 increments in successive cohorts, with one patient per cohort if no dose limiting toxicity (DLT) is encountered. All pts receive vitamin B12 1 mg intramuscular q 8–10 weeks and folic acid 1 mg by mouth once a day beginning at least 7 days prior to pralatrexate. All patients undergo pharmacokinetic testing following their first and second dose of pralatrexate. Results: Between 1/05–12/06, a total of 9 pts have been treated at the following dose levels: 150 (n=1), 190 (n=1), 230 (n=1), and 270 (n=6). Patient characteristics include: 2 male/7 female; median age 63 (range 52–73); KPS 80–90%; all pts had stage 4 NSCLC; 5 pts received 1 prior regimen and 4 pts received 2 or more prior regimens. Grade 3 esophagitis was a DLT in one patient at the 270 mg/m2 dose. Three other patients experienced grade 1–2 mucositis at this dose level without limiting drug delivery. The trial is ongoing, and enrollment is planned at 310 mg/m2 q2w to determine the MTD. Conclusions: When given in combination with vitamin B12 and folic acid supplementation, pralatrexate has been well tolerated in this pt population, with an MTD at least twice as high as achieved in previous phase 1 testing without supplementation. We plan to conduct a phase 2 trial of pralatrexate with vitamin B12 and folic acid supplementation to see if a higher dose will improve efficacy. No significant financial relationships to disclose.
Ifosfamide given once every other week: A clinical and pharmacological study
Authors: Cacheux W. , Gourmel B. , Alexandre J. , Germann N. , Rabillon F. , Goldwasser F. 
Published: March 2020

13008 Background. Ifosfamide (IFM) is a bi-functional alkylator with wide spectrum of activity in solid tumors and has an auto-inductive liver metabolism through P450 cytochromes. Auto-induction might permit a better therapeutic index for combination therapy. Methods. A phase I trial with interpatient dose escalation of a single dose of IFM given every 2 wks in advanced solid tumor pts. IFM, its dechloroethylated and active 4-hydroxy metabolites, were measured at cycle 1 & 2 at the end of infusion, 2 and 5h later, using gas chromatography. IFM elimination was considered as following a monocompartimental model kinetics. Results From January 2004 to June 2006; 20 pts of PS<2 were included :10 F, 10 M, median age 61 years (39–78), median previous chemotherapies: 2 (0–5). Primary tumor was most often ovarian (5), peritoneal (3), sarcoma (2), melanoma (2), or miscellaneous (8). 10 pts received 2.5g/m2 and other 10 pts received 3g/m2. A total of 79 cycles were evaluable for toxicity. median number of cycles: 4 (1–8). No Grade (Gr) 3–4 hematologic toxicity, no alopecia. Gr2 nausea and fatigue were the most common toxicities at 3g/m2. No toxicity-related fatal event was noted. One objective response was noted in pancreatic cancer pt and one sustained CA125 decline in a heavily pretreated ovarian cancer pt. A slight (7–10%) but reproducible decrease of AUC was detectable at cycle 2, at both dose levels, related to auto-inductive metabolism (see table below). The other PK results are available and will be presented (Table). Intra individual variations (large SD) were noticed for each pharmacokinetic (PK) parameter. Conclusions: A slight non dose- dependent but rather patient-dependent auto-induction of IFM metabolism was detected. The toxicity profile allows the development of every 2 wks IFM-based combination therapies. [Table: see text] No significant financial relationships to disclose.
Importance of timing of PET scan after therapy in oncology
Authors: Mullai N. , Baker W. , Simons L. 
Published: March 2020

13014 Background: Growth factors are routine after systemic chemotherapy both as primary and secondary prophylaxis. Similarly PET scan is increasingly used for initial staging and follow-up of response. Timing of both is important since false positive results are noted due to high sensitivity of the test. Methods: Records of four patients with super positive PET scan with diffuse uptake in the axial skeleton were analyzed for the timing of administration of white cell growth factor before imaging and confirmation of bone finding with a follow- up bone scan to rule out mets. Results: Two patients were treated for stage IIIB/IV non-small cell lung cancer, one patient with breast cancer was receiving adjuvant treatment for stage IIIA breast cancer, and the last patient was treated for metastatic pancreatic cancer. All had negative scans for bone mets before the start of treatment. PET scan was done for staging in one patient and evaluation of abnormal CT scan in another, and follow-up of response in two patients. It was inadvertently obtained 10–14 days after the filgrastim/pefilgrastim administration. Based on the unusual uptake in bony skeleton, bone scan was ordered to rule out bone mets in all four patients. Since their bone scans were negative for metastatic disease they were continued on their treatment plan as scheduled. Conclusions: PET scan has been sparingly used until 1990’s due to high cost. Currently Medicare has approved it for wider indications. PET scan in general has high sensitivity and low specificity and false positive results are more common from metabolically active infection and inflammation. Granulocyte colony stimulating factor used with cancer treatments can increase the FDG uptake in PET scan. Diffuse increased uptake in bone marrow by PET scan can be seen in reactive marrow following growth factor therapy. Usually FDG uptake is modest with SUV of less than 3, uniform and diffuse if due to growth factor stimulation in contrast to greater intensity with SUV around 6 with non uniform distribution. Awareness of this pitfalls associated with PET scan allows image interpretation accurately. PET-CT fusion may increase the diagnostic specificity. However timing of the scan in relation to growth factor administration may also help to avoid the unnecessary anxiety and further follow up testing which adds to the health care costs. No significant financial relationships to disclose.
A phase I study of modified irinotecan (CPT-11) plus cisplatin (CDDP) [m-IP] against paclitaxel/carboplatin [TC] -resistant and recurrent ovarian cancer
Authors: Suzuki T. , Morishita M. , Matsuura M. , Fujimoto T. , Tanaka R. , Ito E. , Ebina Y. , Saito T. 
Published: March 2020

13015 Background: CPT-11/CDDP is effective regimen for ovarian cancer. Particularly against ovarian cancer resistant to prior chemotherapy, a 40% response rate was reported (Sugiyama T Cancer Letters, 1998). However, every 4 weeks treatment with CPT-11 day 1, 8, and 15, administration on day 15 was skipped in about 60% due to toxicity, and the relative dose intensity of IP was 66.7% in non-small cell lung cancer (Saito H Am J Clin Oncol 2006). We planed Phase I study, in consideration of the effect of prior chemotherapy in TC-resistant ovarian cancer, a modified CPT-11 (day 1, 8) and CDDP (day 1) for every 4 weeks treatment (m-IP). The aim of this study conducted to examine the dose limiting toxicity (DLT), to evaluate the maximum tolerated dose (MTD), and define the recommended dose (RD) for a phase II study. Methods: Patients with TC-resistant ovarian cancer having a PS 0–1, age 30–75 years, normal organ functions, and written informed consent. CPT-11 was administered intravenously over 90 minutes on day 1 and day 8, plus CDDP was day 1, repeated every 4 weeks. The dose escalation schedule was defined: Doses of CPT-11/CDDP (mg/m2) were 60/60 at level 1, 70/60 at level 2 and 70/70 at level 3. DLT were determined as Grade 4 hematological toxicity and = Grade 3 non-hematological toxicity occurred, and when dosing on day 8 was delayed for more than 8 days due to toxicity. Results: Nine patients were enrolled (level 1/2/3: 3/3/3). DLTs, at level 1 and 2, no patients developed. At level 3, grade 3 nausea and vomiting and delayed treatment on day 8 due to anorexia, were observed in all of 3 patients. Therefore, MTD was determined to be level 3 and RD was determined to be level 2 (CPT-11: 70mg/m2, CDDP: 60mg/m2). Major =Grade 3 toxicities observed were leukopenia, neutropenia, nausea, and vomiting. No Grade 4 hematological toxicities were observed. Diarrhea was mild. Antitumor effect at RD was observed in 1 patient with CR, 1 patient with PR and 1 patient with PD. Conclusions: The MTD of m-IP was CPT-11 70mg/m2 and CDDP 70mg/m2 (level 3), the RD was CPT-11 70mg/m2 and CDDP 60mg/m2 (level 2). Preliminary response are promissing associated with tolerable toxicity for TC-resistant and recurrent ovarian cancer. A Phase II study is currently conducted. No significant financial relationships to disclose.