bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival differences in patients with brain metastases according to breast cancer subtypes
Authors: Nam B. , Lee K. , Kim T. , Ro J. 
Published: March 2020

11507 Background: Brain metastases (BM) occur in as many as one-third of patients with metastatic breast cancer (MBC). Incidences and prognoses by triple receptor subtypes in BM have not been well delineated. Methods: Retrospectively, prognoses were assessed according to clinical characteristics, triple receptor subtypes, and receipt of trastuzumab therapy by univariate and multivariate analyses. ER/PR/HER2 were tested by IHC with HER2 FISH for IHC 2+ and for all 118 consecutive primary BC. Results: Between 8/2001 and 4/2006, 138 of 805 pts (17.1%) with MBC presented with BM at NCC Korea. More pts with triple negative and HER2+ tumors developed BM (see table ). The median age was 47 years. They were single (9%), multiple (80%), or leptomeningeal disease with or without multiple BM (11%). As initial therapy, 104 pts received WBRT, 8, intrathecal therapy (IT), 9, WBRT with IT, and 17 others. Of 56 HER2+ pts, 45 received trastuzumab either before (n=25) or after (n=13), or continuously before and after BM diagnosed (n=7). By 10/2006, 117 pts died with a median survival of 4.5 months. Multivariate analyses indicated age, tumor receptor subtypes, leptomeningeal presentation and number of extracranial disease sites as significant factors. Receipt of trastuzumab therapy after BM was a significant variable for survival in HER2+ diseases (3.8 vs. 13.4 mo, p=0.0000). Pts with triple negative subtype lived shortest compared with other types (p=0.0035). Conclusions: More pts with triple negative and HER2+ disease developed BM. HER2+ disease gained a significant survival benefit by trastuzumab therapy. Supported by NCC Grant 0610240 and 0510520. [Table: see text] No significant financial relationships to disclose.
Cardiotoxicity of weekly trastuzumab (T) plus epirubicin (E) and paclitaxel (P) for HER2-positive locally advanced (LA) and/or metastatic (M) breast cancer (BC): A feasibility phase II study
Authors: Nisticò C. , Bria E. , Cuppone F. , Carpino A. , Vaccaro V. , Barberi S. , Sperduti I. , Giannarelli D. , Cognetti F. , Terzoli E. 
Published: March 2020

11509 Background: The introduction of T for patients (pts) overexpressing HER-2 changed the natural history of BC. The adjunction of T to anthracyclines and taxanes for both LABC and MBC provided a significant incidence of unexpected cardiotoxicity. Given the low cardiac toxicity in our previous experience with weekly ET in unselected MBC pts, a feasibility phase II study aimed to cardiotoxicity was planned. Methods: Pts affected by untreated LABC/MBC overexpressing HER-2 by FISH/CISH amplification or 3-positive Dako- Test, underwent weekly T (4–2 mg/kg/week), day 1, and E (25 mg/m2/week) plus P (80 mg/m2/week), day 2, plus G-CSF support, for 16/24 consecutive weeks in absence of progression or toxicity, in LA/M pts, respectively. Pts with significant cardiac disease/L-FEV<50% were excluded. Primary endpoint was the rate of pts with L-FEV reduction >10% after 12 weeks. An optimal 2-stage Simon design was applied. With a power of 90% at a 5% significance level, assuming a toxicity rate of 30% as unacceptable, and less than 10% as acceptable, an initial group of 15 pts was required; with 11 pts with no toxicity, a second step with further 21 pts (total 36) was planned. Non-cardiac toxicity and activity were evaluated as secondary end-points. Results: From May 2004 to November 2006, 15 pts entered the study. Patient characteristics: median age=47 (range 37–69); LABC/MBC=4/11; positive hormonal receptor 8/7; menopausal pre/post=7/8; PS 0/1=14/1; number of met sites 1/2/3=7/6/2. Median baseline- and post-week-12-L-FEV was 69% (range 64–77) and 65% (range 61–76), respectively. With a median number of courses of 13 (range 8–24), 3 pts had a >10% L-FEV reduction (20%), with an overall median L-FEV reduction of 5.2%. No EKG alteration or specific symptoms were registered. With a 17-months median follow-up, 13 pts were evaluable for response. Eight response (61.5%, 95% CI 9- 87) were documented, with a median response duration of 9 months. No grade 3–4 toxicity were registered, with the exception of severe alopecia. Conclusions: The weekly administration of T plus E and P is extremely tolerable, also with regard to L-FEV reduction. The low L- FEV reduction rate allowed entering the second step of the study. No significant financial relationships to disclose.
Longitudinal analysis of trastuzumab use in metastatic breast cancer
Authors: Hammerman A. , Klang S. , Liebermann N. , Ben-Baruch N. 
Published: March 2020

11513 Background: Six years after including Trastuzumab in the Israeli ‘National Health Basket‘ (NHB) for metastatic breast cancer (MBC), we evaluated its ‘real-life‘ use in terms of duration of treatment (DOT) and survival after initiation of treatment. Methods: The computerized database of Clalit Health Services’ (CHS), the largest Israeli sick fund, was used to determine DOT and survival (at Dec. 31, 2005), in all CHS patients with MBC that started Trastuzumab therapy during years 2000–2003. Results: * At Dec. 31, 2005. ** However, most received AC as adjuvant. Conclusions: A longitudinal analysis of Trastuzumab use shows a difference of 40–100% between the median and mean DOT. This difference is attributed to a sizeable proportion (∼15%) of patients that are “long-term responders” and are treated for more than 24 months. In these patients, we can assume that the HER-2 amplification is an essential transforming event. We recommend investigating the molecular characteristics of long-term responders. [Table: see text] No significant financial relationships to disclose.
Single-agent docetaxel (TXT) as first-line treatment in metastatic breast cancer (MBC)
Authors: Guarneri D. , Ratti R. , Venturino A. , Addamo G. , Coccorullo Z. , Colloca G. , Campora E. 
Published: March 2020

11515 Background: Historically anthracyclines have been considered the most active agents in metastatic breast cancer (MBC). Docetaxel (TXT) has challenged this belief. Aims: Evaluate response rates, toxicity and time to progression in patients with MBC receiving single agent TXT as first line treatment. Methods: MBC patients received first line single agent treatment according to one of the following schedules: TXT 35 mg/m2 iv weekly for 6 wks q 8 wks (Group 1) or TXT 100 mg/m2 iv day 1 q 3 weeks (Group 2). Adjuvant chemotherapy was FAC (600,50,600) day 1 q 21 days for 6 courses in all cases so treated. Results: Conclusions: It appears that results with single agent TXT obtained in clinical practice are comparable to those reported in Phase II-III trials (Group 1 and Group 2, respectively ) using the same regimens. [Table: see text] No significant financial relationships to disclose.
Fixed dose rate (FDR) gemcitabine as radiosensitizer for newly diagnosed glioblastoma multiforme (GBM): Preliminary results of a phase II study
Authors: Fabi A. , Felici A. , Mirri M. A. , Metro G. , Vidiri A. , Pace A. , Carosi M. A. , Cognetti F. , Occhipinti E. , Carapella C. M. 
Published: March 2020

12502 Background: In a previous phase I study (ASCO 2006), where FDR Gemcitabine at 10/mg/m2/min was tested in association with radiotherapy (RT) for the treatment of newly diagnosed GBM, a maximum tolerated dose of 175 mg/m2/wk was identified. Methods: After surgery for GBM (either citoreduction or sterebiopsy), patients were treated with fractionated focal RT at a daily dose of 2.0 Gy per fraction, five days per week for six weeks (total dose of 60 Gy). FDR Gemcitabine at 175 mg/m2/wk was given concomitantly starting 24–72 hours prior to RT and then for the whole duration of RT. An MRI performed at 7 and 40 days from the end of chemo-radiotherapy was used for activity assessment. Standard oral temozolamide 150–200 mg/m2 was administrated following the combined treatment. Results: From 07/2004 16 patients (9 male, 7 female) have been enrolled. Characteristics of patients were: median age 57 years (42–72), median KPS at baseline 90 (70–100), surgery/stereobiopsy 14/2. Median time from diagnosis to initiation of Gemcitabine was 45 days (28–54). Among the 14 evaluable patients 3 (21.4%) partial responses, 7 (50%) stable disease and 4 (28.5%) progressive diseases were recorded. At a median follow up of 18 months (2–33) time to progression was 6 months (1.5–24). Toxicity was manageable with only one G3 neutropenia and hypertransaminasemia in two patients respectively. Grade 1 hypertransaminasemia was registered in 6 patients (43%). Conclusions: These preliminary results show that in patients with newly diagnosed GBM, radiosensitizing FDR Gemcitabine at 175 mg/m2/wk is a well tolerated regimen with an interesting activity. Accrual is ongoing and final results will be presented at the meeting. No significant financial relationships to disclose.
The role of MGMT promotor hypermethylation as a predictive factor for response to temozolomide in recurrent high-grade glioma
Authors: Sadones J. , Michotte A. , Chaskis C. , In ’t Veld P. , Califice S. , Bierau K. , Svensson C. , De Grève J. , Neyns B. 
Published: March 2020

12509 Background: Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltransferase) DNA-repair gene by promotor hypermethylation (MGMT-meth) compromises DNA repair of high-grade glioma (HGG) and has been associated with a survival benefit in patients treated with temozolomide (TMZ) for newly diagnosed glioblastoma multiforme (GBM). It remains undetermined if the MGMT-meth status correlates with response to temozolomide at recurrence and whether extended dosing of TMZ (known to deplete MGMT in peripheral blood mononuclear cells) can overcome resistance in unmethylated HGG. Methods: We are investigating the MGMT-meth status on glioma tissue samples collected at diagnosis from 64 patients (pts). Fifty pts were treated at the time of recurrence with conventional TMZ (5 out of 28d regimen) and 14 pts with extended dosing of TMZ (100 mg/m2/d, 21 out of 28d regimen). Following DNA isolation from archival glioma tissues by phenol/chloroform extraction and a bisulphite conversion of genomic DNA, real-time methylation-specific PCR quantification of the methylation status of the MGMT promotor region is performed by OncoMethylome Sciences S.A. (according to OMS proprietary methodology). Results: At present, results have been obtained for 15 pts (13 M/ 2 W, median age: 46y). From 3 pts a biopsy at recurrence was available for analysis. The result was discordant with the MGMT-meth status at diagnosis in 2 pts (1x meth to unmeth and 1x unmeth to meth). Of the 6 (40%) pts with MGMT-meth gliomas, none had immediate progression on TMZ (respectively 4x SD, 1x CR, 1x PR). Of the 9 pts with an unmethylated MGMT promotor, 4 pts had immediate progression on TMZ and 5 pts had SD (of which 4 had been treated with the 21/28d regimen). All pts, except one, with MGMT-meth had a TTP that was above the median of our study population. The two pts with an MGMT-unmeth status that had a TTP above the median had received the extended dosing regimen. Conclusions: Our preliminary data indicate that MGMT promotor hypermethylation at diagnosis might correlate with sensitivity to TMZ in the recurrent setting. Extended dosing of TMZ might be more active against MGMT-unmethylated glioma. Final data from this study will be available for presentation at the meeting. No significant financial relationships to disclose.
Can a conventional schedule of radiation therapy be administered to elderly patients with glioblastoma multiforme?
Authors: Manfrida S. , D’Agostino G. R. , Anile C. , Mantini G. , Colicchio G. , Gambacorta M. A. , De Renzi F. , Valentini V. , Smaniotto D. , Balducci M. 
Published: March 2020

12516 Background: We retrospectively evaluate the tolerance and the efficacy of a conventional schedule of radiotherapy in elderly patients with glioblastoma multiforme (GBM). Methods: Eighty-three consecutive patients affected by glioblastomas were treated between 2001 and 2006. We divided our series in two groups: patients under 65 years (n=52) and patients ≥ 65 years old (n=31). In the elderly group, median age was 68 years (range, 65–80). 17 patients (54,8%) were female, 14 male (45,2%); 20 patients (64,5%) <70 years, 11 patients (35,5%) ≥70 years. Among the younger patients, median age was 51 years (range 25–64), male/female ratio 32/20 (61.5%/38.5%).Twenty-seven out of 31 elderly patients (87,1%) were treated with conformal radiotherapy (CRT, 5940 cGy, 180 cGy/day; CTV2: tumor bed + residual tumor if present + oedema, 3960 cGy; CTV1: tumor bed + residual tumor if present + margins, 1980 cGy). Four out of 31 patients received an intensification dose of xxxx cGy by stereotactic conformal radiotherapy (SRT, 12,9%); among the younger patients, 25/52 were treated with CRT (48,1%) and 27/52 with SRT (51,9%). Concomitant and adjuvant chemotherapy was administered by temozolomide (TMZ).Toxicity was evaluated according to RTOG score. Survival analysis were performed using Kaplan-Meier method and log-rank testing was used for comparison of groups. Results: In the elderly group, neurological acute toxicity was observed in 6/31 patients (19,4%), with grade 3 in two patients. In the under 65 group, 5/52 patients (9,6%) had neurotoxicity (Grade 3 in two patients).This difference was not statistically different.At a median follow-up period of 28 months (range, 3–61), median progression-free survival (PFS) was 11 months in the ≥65 group and 10 months in the under 65 group; median overall survival (OS) was respectively 17 months and 22 months. 1- year survival was respectively 77.6% and 74.5%. Conclusions: In our analysis age did not seem to be a limiting factor in the choice of the therapeutic strategy for patients with glioblastoma multiforme. No significant financial relationships to disclose.
Re-irradiation using high precision radiotherapy and concomitant temozolomide in patients with recurrent glioma: Re- challenge with radio-chemotherapy
Authors: Combs S. E. , Schulz-Ertner D. , Welzel T. , Bischof M. , Debus J. 
Published: March 2020

12517 Background: This study was aimed to assess the toxicity and efficacy of radiochemotherapy (RCHT) with temozolomide performed as re-irradiation in patients with recurrent glioma. Patients and Methods: We treated 17 patients with RCHT for recurrent glioma between July 2005 and December 2006. Nine patients were female, eight were male. Pathology evaluation revealed WHO grade II astrocytoma in 5, anaplastic astrocytoma in 4 and glioblastoma multiforme (GBM) in 7 patients. One patient suffered from gliosarcoma. Median age at primary diagnosis was 33 years (range, 6–60 years). In 4 patients surgery had been performed as total resection, subtotal resection in 9 and as a biopsy in 4 patients. Median doses of radiotherapy (RT) of 60 Gy had been applied. Prior treatment with temozolomide either as RCHT or as chemotherapy alone for tumor progression had been performed in 8 patients. The median time interval between primary RT and re-irradiation was 29.5 months (range 5–180 months). Re-irradiation was performed as high precision radiotherapy using fractionated stereotactic radiotherapy (FSRT) in 16 patients with a median total dose of 36 Gy (range, 28–36 Gy); in one patients stereotactic radiosurgery (SRS) was applied for a very small lesion with a single dose of 18Gy/80% isodose. The target volume was defined as the area of contrast enhancement on T1-weighed MRI-scans including a safety margin of 0.5 to 1 cm. Chemotherapy was applied concomitantly in a median dose of 50 mg/m2 per day (median of 100mg TMZ qd); in 14 patients RCHT was followed by adjuvant cycles of temozolomide. Results: Treatment could be completed in all patients without interruptions due to side effects; no severe acute or long-term toxicities were observed. One patient with recurrent GBM showed tumor progression during therapy and treatment was stopped at 32 Gy out of 36 Gy. Progression-free survival was 56% at 6 months after FSRT; survival after FSRT was 75% at 6 months. Median overall survival was 39 months, with 92% at 1 and 2 years. Conclusions: High-precision RT and concomitant temozolomide is safe and effective when performed as re-irradiation in recurrent glioma. The data demonstrate that re-challenge with temozolomide justifies further evaluation. No significant financial relationships to disclose.
Efficacy of different regimens of adjuvant radiochemotherapy for glioblastoma
Authors: Scheda A. , Finjap K. , Lohr F. , Tuettenberg J. , Brockmann M. , Wenz F. , Wenz F. 
Published: March 2020

12531 Background: Purpose/Objective(s): We retrospectively analyzed the impact of different temozolomide (TEM) regimens in a group of patients treated for glioblastoma compared to patients only receiving postoperative radiotherapy. Methods: Between 01/2000 and 12/2003, 75 consecutive patients underwent radiotherapy. 52 patients received exclusively radiotherapy, 17 patients radio-chemotherapy with low-dose TEM (20 mg/m2) given in 2 daily single doses in combination with an inhibition of cyclooxygenase-2, 6 patients radio-chemotherapy with high-dose TEM (50mg/m2) followed by adjuvant TEM (150–200mg/m2) for 5 days during each 28-day cycle up to 6 cycles. Patients were monitored with MRI every 8 weeks. Aggressive treatment for recurrent disease consisted of re-operation, re-irradiation (fractionated stereotactic radiotherapy 12 x 3 Gy) and/or chemotherapy. Results: The groups treated with high-dose TEM and low dose TEM showed the longest overall survival (OS) (median OS 21 months and 17 months, respectively). Median OS of 9 months for the radiation alone group was condiserably shorter. The same positive trend on prolonged OS was confirmed when either only patients submitted to maximally radical resection or for patients with KPS>70 were considered. No statistically significant difference was observed in terms of progression free survival (PFS). Conclusions: Patients treated with adjuvant TEM either inside or outside study protocols had survival times similar to other reports or randomized studies. The absence of influence of TEM on PFS could either depend on the unavoidable drawbacks and bias of retrospective investigations or on the definition of relapse used. Aggressive and early treatment for recurrent disease results in median survival times approaching 2 years. No significant financial relationships to disclose.
Second surgical intervention and continuous adjuvant therapy with temozolomide improved survival time in patients with GBM
Authors: Urs Sebastian H. 
Published: March 2020

12536 Background: GBM is among the most debilitating malignant disease. A combination of surgery followed by concurrent radiochemotherapy (RCT) followed by adjuvant TMZ improves overall survival (OS) & progression-free survival (PFS). This retrospective exploratory analysis evaluated the effect of different TMZ treatment regimens & repeated surgical interventions on clinical outcome in patients with GBM. Methods: 28 pts with WHO Grade IV GBM diagnosed between 1998–2005 (age: 27–68 years) underwent maximum resection feasible, followed by RT (40–80Gy). 18 pts received standart adjuvant TMZ 150–200 mg/m2 /d, d1–5/ 28d (TMZ-S) after initial surgery. 10 patients received no further treatment, until relapse. Results: 2/28 pts have not yet relapsed and continue to receive adjuvant TMZ-S (>40 cycles, PFS 5.2 + yrs & >73 cycles; PFS 7.5+ yrs). In the 26 relapsed pts, PFS was 13.1 ± 13.0 mos (n=16, range: 2 - 48 ) in pts receiving TMZ-S compared to 9.5 ± 11.7 mos (n=10; range: 0.5 - 41) in pts with no adjuvant TMZ. At relapse, 12 had a second surgery with additional TMZ-S or TMZ 75 mg/m2/d, d1–14/21days (TMZ-LD) . 14 pts did not have a second surgery and were further treated with either TMZ-S or TMZ-LD. OS was 30.6 ± 13.7 mos in pts who received adjuvant TMZ-S followed by a change to TMZ-LD at relapse (n=5) compared to 18.3 ± 20.0 mos in pts who continued TMZ-S after relapse (n=6). Overall, the longest OS was observed in pts who received adjuvant TMZ-S with a second surgery followed by TMZ-LD at relapse (n= 2: PFS 57 & 59 mo). The shortest OS was observed in pts who had neither adjuvant TMZ-S nor additional surgery (n=5; 3–15 mos). A single outlier in this group was a pt with an OS of 58 mos. Conclusion: Best outcome in our pts with relapsed GBM was observed in those who received initial resection/RT followed by adjuvant TMZ-S with subsequent re-resection and TMZ- LD at relapse. Pts unable to undergo re-resection appeared to still benefit from a change to TMZ-LD at relapse. No significant financial relationships to disclose.
Open-label study to assess effect of omeprazole (O) on pharmacokinetics of bortezomib (B) in subjects with advanced solid tumors, NHL, or multiple myeloma
Authors: Quinn D. I. , Nemunaitis J. , Fuloria J. , Britten C. D. , Gabrail N. Y. , Yee L. , Acharya M. , Chan K. C. , Bishop P. , Dudov A. P. 
Published: March 2020

13000 Background: Omeprazole (O), an over-the-counter proton pump inhibitor, is also a potent inhibitor of cytochrome P450 (CYP) 2C19, an enzyme responsible for the metabolism of many drugs including bortezomib (B; VELCADE®). This study sought to evaluate potential drug interactions between omeprazole and bortezomib. Methods: Between January 2005 and August 2006, 18 men and 9 women were randomized to receive B 1.3 mg/m2 iv alone on Days 1, 4, 8, and 11 of a 21-day cycle or B + O 40 mg (2 x 20 mg capsules) on the mornings of Days 6–10 and the evening of Day 8 in Cycle 1, crossing over to receive the other treatment in Cycle 2. Baseline plasma samples were collected before B administration on Day 1 Cycle 1 and Day 8. Results: 17 patients completed both cycles and were evaluable for pharmacokinetics (PK) analysis. The PK of bortezomib with and without omeprazole overlapped and the peak concentrations and time to reach peak concentrations were similar (Table). As observed in other studies of B, there was a high degree of inter-subject variability (B alone, %CV = 64.7; B + O %CV = 60.3); however, differences in mean exposure values between treatments were within the degree of inter- subject variation. There was no increase in adverse events related to bortezomib as a result of treatment with O. In both groups over 95% of patients had over 80% 20S proteasome inhibition. No meaningful relationships were apparent among CYP gene polymorphisms (2C19, 2D6, 3A4, 3A5) and PK endpoints (AUC8 and Cmax) or pharmacodynamic (PD) endpoints (AUE72 and Emax) in either group or both groups combined. Conclusion: Addition of O to B did not alter PK, PD or safety parameters. Clinically significant drug interaction is unlikely when B is co-administered with O or other CYP2C19 inhibitors. [Table: see text] No significant financial relationships to disclose.