bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathological correlation (CC) and outcome of breast cancer patients (pts) with resected brain metastasis (BM)
Authors: Ibrahim N. K. , Nguyen G. , Suki D. , Hennessy B. , Montero A. , Sarriera J. E. , Symmans F. , Valero V. , Sawaya R. , Aldape K. 
Published: March 2020

656 Background: We aimed at determining the pathologic features of metastatic breast lesions to the brain, and their correlation with the primary tumor, and their effect on postneurosurgical survival (PNS). Methods: Tissue samples from 123 pts who underwent surgical resection of BM at MDACC between 1984–2004, were examined for estrogen receptor-α (ER) by IHC and HER2 by FISH or IHC. Pts’ medical records were retrospectively reviewed for CC. Results: Median (med) age at BM diagnosis was 51 years. The med time from primary diagnosis to BM was 33 months (Range (R)0–304). Infiltrating ductal cancers were found in 89%. ER was negative and HER2 amplified in 73% and 37% of BM, respectively; ER-/Her2- was seen in 43%, ER-/Her2+ in 30%, ER+/Her2+ in 6%. Concordance of ER and HER2 status between primary and BM were both 88% (p=NS, for discordance). ER positivity was associated with a longer primary diagnosis to BM interval [med 39 months (R, 0–213) vs. 29 months (R, 0–304) in the ER- pts; p=0.02]; HER2 amplification was not (p=0.82). The med PNS was 11.2 months (R, 9.0–13.5) for 112 pts with no pre- craniotomy brain radiation. Pts with ER+ metastases experienced apparent longer PNS survival than ER- pts [med 18.9 months (95% CI, 4.8–33.1) vs. 9.9 months (95% CI, 7.6–12.1 months), respectively, p=0.06], as did those with HER2-amplified BM [med 13.8 months vs. 9.9 months, respectively; p=0.10]. Pts aged 45 to <60 years had significantly longer pns survival (med 15.5 months) than younger or older pts (med 9.5 and 5.1 months, respectively), p≤.05 for all pair- wise comparisons. In mutivariate analyses correcting for age, functional status, and systemic tumor burden, neither ER nor HER2 status were independent predictors of pns. Of the 38 patients with HER2-amplified tumors and no pre- craniotomy radiation, 14 received trastuzumab (Tz) prior to initial neurosurgery. These 14 pts had longer PNS compared to those with HER2-amplified tumors not receiving Tz [median, 25.4 months vs. 10.7 months, respectively, p=NS). Conclusions: ER and HER2 positivity were highly concordant between primary and BM. Resected BM were more likely to be ER- or HER2-amplified. ER positivity and HER2 amplification were not significant independent predictors of PNS, though both showed a strong trend in univariate analyses. Middle age group pts had the best PNS survival. No significant financial relationships to disclose.
Darbepoetin alfa for treating anemia in low-risk myelodysplastic syndrome patients: Interim results after 27/28 weeks
Authors: Paquette R. , Gabrilove J. , Lyons R. , Mushtaq C. , Sekeres M. , Lam H. , Dreiling L. 
Published: March 2020

6564 Background: Patients (pts) with myelodysplastic syndrome (MDS) disorders often develop anemia, resulting in increased transfusions and fatigue. Using the erythropoiesis-stimulating agent (ESA) epoetin alfa to treat anemia in low-risk MDS pts results in an average response rate of 30% (40% when used with G-CSF). Pilot studies suggest that 150 or 300 mcg/week (wk) darbepoetin alfa (DA) can raise hemoglobin (Hb) levels in anemic MDS pts. Methods: This fully enrolled (n = 209), phase 2, single-arm, 52-wk ongoing study is examining DA 500 mcg every 3 weeks (Q3W) for treating anemic pts (Hb ≤ 11 g/dL) with low- or intermediate-risk MDS (IPSS definition). The study’s primary endpoint is the proportion of pts achieving an erythroid response by 13 wks. Other endpoints include the proportion of pts achieving an erythroid response by 27/28 wks and change in both Hb levels and FACT-F scores. Results are stratified by whether pts received ESA therapy before enrollment: ESA-naïve (ESA-N) vs ESA-treated (ESA-T). Results: Previous interim data suggested that low-risk MDS pts can achieve a major erythroid response after 13 wks of DA 500 mcg Q3W. This is the first reported summary of results from a planned interim analysis after 27/28 wks of treatment (n = 129). Of 84 ESA-N pts, 51% were men, 86% were white, and the average (SD) age was 74.1 (9.7) years; the 45 ESA-T pts had similar demographics. During 27/28 wks of treatment, a majority of pts achieved a major erythroid response. ESA-N pts had a mean (SD) 1.2 (1.4) g/dL rise in Hb levels from BL and a clinically significant increase in FACT-F score from BL ( Table ). Of the 129 pts analyzed after 27/28 wks, 83% reported an adverse event (AE) and none reported serious treatment-related AEs or thrombotic events (of 189 pts analyzed after 13 wks, 1 pt reported a serious treatment-related AE). Conclusions: These interim results suggest that DA 500 mcg Q3W is well tolerated and can raise Hb levels in anemic, low-risk MDS pts. Final 27/28-wk data from all enrolled pts (n = 209) will be shown. [Table: see text] [Table: see text]
A study of factors determining outcome of patients receiving third line chemotherapy for metastatic breast cancer: The Royal Marsden Hospital experience
Authors: Kuciejewska A. , Banerji U. , Walsh G. , Ashley S. , O’Brien M. , Johnston S. , Smith I. 
Published: March 2020

657 Background: Metastatic breast cancer is increasingly treated with multiple lines of chemotherapy. We studied the factors determining the outcome of patients receiving third line chemotherapy for metastatic breast cancer Methods: This is retrospective study of 149 consecutive patients from the Royal Marsden Hospital chemotherapy database recorded to have received third line chemotherapy for metastatic breast cancer. The chemotherapy regimens and best response to chemotherapy for all three lines of chemotherapy were recorded. The time to progression (TTP) and survival after third line chemotherapy were also studied. Chi square and log rank tests were used to analyse differences in response rates (RR) and (TTP)/survival respectively. Results: 149 patients were studied with a median age of 52 (range 25 -80). The median TTP and survival was 4 months (range 1–25) and 8 months (range 1–52) respectively. Eighteen different chemotherapy regimens were used. The RR for third line chemotherapy was 30.2% (45/149). There was no significant difference in the TTP and survival of patients treated with different chemotherapy regimens (p= 0.82 and 0.44) respectively. We identified a subgroup of patients who had a poor outcome after third line chemotherapy. These patients did not respond to the first two lines of chemotherapy and had a response rate of 20.2% (10/49) compared to the rest of the cohort, 35% (35/100), p= 0.068. The TTP (3 Vs 4 months, p = 0.033) and survival, (6 Vs 9 months, p = 0.027) of this subgroup was significantly shorter than the rest of the cohort. The median time to death after progression in this subgroup was 2 months. Conclusions: The chemotherapy regimen used does not influence RR, TTP or survival in patients receiving third line chemotherapy for metastatic breast cancer. Patients not responding to the first two lines of chemotherapy have a significantly shorter TTP and survival. Best supportive care or experimental chemotherapy should be considered as options for these patients. No significant financial relationships to disclose.
Prognostic significance of bcl-2 expression in stage III breast cancer patients who received doxorubicin and cyclophosphamide followed by paclitaxel as adjuvant chemotherapy
Authors: Lee K. , Kim B. , Lee S. , Han W. , Kim D. , Im S. , Kim T. , Park I. A. , Noh D. , Bang Y. 
Published: March 2020

670 Background: Bcl-2 is an anti-apoptotic marker and regulated by hormonal receptor pathways in breast cancer. We performed this study to assess the prognostic significance of ER, PR, p53, c-erbB2, bcl-2, Ki-67, and EGFR as a marker for relapse in breast cancer patients who received same adjuvant therapy in a single institution. Methods: A cohort of 154 curatively resected breast cancer patients who had 4 lymph nodes or more and received doxorubicin and cyclophosphamide followed by paclitaxel (AC/T) as adjuvant chemotherapy was analyzed for clinicopathologic characteristics including disease-free survival (DFS). Patients with ER and/or PR expression received 5 years of tamoxifen following AC/T. The markers were analyzed by immunohistochemistry. Results: Median f/u duration was 25 months and 32 patients (20.8%) had recurrences. Stage (IIIa vs. IIIc) affected recurrences significantly, however, types of surgery, histology, histologic grade, presence of endolymphatic emboli, or close resection margin did not. Among the immunohistochemical markers, bcl-2 expression was the only one to be associated significantly with prolonged DFS (median 54 mo in bcl-2 (−) vs. not reached in bcl-2 (+); p=0.016). Furthermore, bcl-2 was an independent prognostic factor for DFS in multivariate analysis. Bcl-2 expression was significantly correlated with ER expression (p<0.001), and inversely correlated with c-erbB2 overexpression (p=0.027). Patients with both ER and bcl-2 expression had a longer DFS compared to the other patients (not reached vs. 54 mo, p=0.019). Patients with bcl-2 expression had a significantly longer DFS even in ER (+) subgroups (not reached vs 54 mo; p=0.011). Patients with c-erbB2 overexpression, ER (−) and bcl-2 (−) had a shorter DFS than the others (38 mo vs. not reached; p=0.029). Conclusions: In our homogenous patient cohort, bcl-2 expression was correlated with ER expression, and inversely correlated with c-erbB2 overexpression. Bcl-2 was an independent prognostic factor for DFS in curatively resected stage III breast cancer patients. No significant financial relationships to disclose.
Same day administration of pegfilgrastim with dose dense doxorubicin in early breast cancer patients
Authors: Vance K. T. , Carpenter J. 
Published: March 2020

671 Background: Pegfilgrastim is indicated to decrease the incidence of febrile neutropenia in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy. In licensing studies, patients received a single dose of pegfilgrastim on day 2 of each chemotherapy cycle, which added an extra visit for day 2 administration. We administered pegfilgrastim to a series of early breast cancer patients on the same day of chemotherapy. We reviewed charts retrospectively to assess both efficacy and safety. Methods: Data on blood counts, toxicity and chemotherapy dosing was collected from July 1, 2003 to May 6, 2005 for all patients with early breast cancer who received sequential or combination doxorubicin, cyclophosphamide and paclitaxel on a 14 day schedule. Herceptin was given with paclitaxel and/or cyclophosphamide in 2 patients. Results: 64 patients with a median age of 50 years (range 22–67 years) were treated. 14 patients had stage I disease, 39 stage II and 11 stage III disease. Forty-one patients were treated postoperatively and 23 preoperatively. 211 cycles of doxorubicin were administered. After administration of doxorubicin, pegfilgrastim 6 mg s.c. was given on the same day. The lowest absolute neutrophil count on day 14 after doxorubicin was 1693/mm3 with no episodes of febrile neutropenia. The highest absolute neutrophil count was 23,671/mm3. The only dose reductions were five doxorubicin doses for grade 1–2 mucositis. Grade 1–2 nausea and vomiting was the most common toxicity seen after doxorubicin. Grade 1 bone pain was the most common side effect seen after pegfilgrastim occurring in 13/64 patients. There was no grade 3 or 4 toxicity of any kind. Conclusion: Pegfilgrastim administered on the same day as doxorubicin on a 14 day schedule was both safe and effective. Side effects were mild and included bone pain most likely attributable to pegfilgrastim. Neither granulocytopenia nor febrile neutropenia were seen and no treatments were delayed or postponed. Pegfilgrastim given on the same day as chemotherapy was effective in maintaining adequate granulocyte counts to allow treatment 14 days later and to avoid infection from granulocytopenia. Toxicity from pegfilgrastim was mild and tolerable. [Table: see text]
Lung Adjuvant Cisplatin Evaluation (LACE): A pooled analysis of five randomized clinical trials including 4,584 patients
Authors: Pignon J. P. , Tribodet H. , Scagliotti G. V. , Douillard J. Y. , Shepherd F. A. , Stephens R. J. , Le Chevalier T. 
Published: March 2020

7008 Background: Several recent trials have shown a benefit of adjuvant cisplatin-based chemotherapy on overall survival (OS) in patients with non-small cell lung cancer (NSCLC). The aim of the Lung Adjuvant Cisplatin Evaluation (LACE) is to identify treatment options associated with a higher benefit, or groups of patients benefiting more from adjuvant chemotherapy. Methods: Individual patient data were collected and pooled from the five largest trials (ALPI, ANITA, BLT, IALT and JBR10) of cisplatin-based chemotherapy in completely resected patients, conducted after the NSCLC-meta-analysis (BMJ 1995, update ongoing). The interactions between patient subgroups or treatment types and chemotherapy effect on OS were analysed using hazard ratios (HR) and logrank tests stratified by trial. Results: With a median follow-up of 5.1 years, the overall HR of death was 0.89 (95% confidence interval [CI]: 0.82–0.96; p<0.005) corresponding to a 5-year absolute benefit of 4.2% with chemotherapy. There was no heterogeneity of chemotherapy effect among trials. The benefit varied with stage (test for trend, p=0.046) with the HR for stage I-A 1.41 [95% CI: 0.96–2.09], stage I-B 0.93 [0.78–1.10], stage II 0.83 [0.73–0.95] and stage III 0.83 [0.73–0.95]. The effect of chemotherapy did not vary significantly (test for interaction, p=0.10) with the associated drugs: vinorelbine (HR=0.80 [0.70–0.91]) etoposide/vinca-alcaloide (0.93 [0.80–1.07]) or other (0.98 [0.84–1.14]). There was no interaction between chemotherapy and sex, age, planned radiotherapy or planned total dose of cisplatin. Conclusions: Adjuvant cisplatin-based chemotherapy improves survival in patients with NSCLC. This benefit depends on stage and is greatest in patients with stages II and III. Our analysis suggests that platinum-based adjuvant chemotherapy may not benefit stage I-A patients. Results of disease-free survival will be presented at the meeting. Supported by PHRC and LNLCC [Table: see text]
Immunohistochemical staining of the Excision Repair Cross-Complementing 1 (ERCC1) protein as predictor for benefit of adjuvant chemotherapy (CT) in the International Lung Cancer Trial (IALT)
Authors: Soria J. , Haddad V. , Olaussen K. A. , Fouret P. , Dunant A. , Filipits M. , Popper H. H. , André F. , Le Chevalier T. , Brambilla E. 
Published: March 2020

7010 Background: Adjuvant cisplatin-based chemotherapy improves survival in patients with completely resected non-small-cell lung cancer, but no clinical or biological predictor of the benefit of CT has yet been validated in large trials. ERCC1 is a highly conserved excision nuclease within the nucleotide excision repair (NER) pathway and is essential for efficient repair of DNA-adducts induced from alkylating agents. Methods: Using a standard protocol of immunohistochemistry, we evaluated ERCC1 expression in 783 resected tumor tissues from patients enrolled in the IALT. For each case, a semi-quantitative histology score (H-score) was calculated on the basis of both the percentage of positive tumor nuclei and staining intensity. The median value of H-scores was a priori chosen as the cut-off point to classify ERCC1 positive and negative tumors. Overall survival was analyzed with a Cox model adjusted on clinical and pathological factors. Results: After immunostaining, 761 out of 783 cases (97%) were of sufficient quality for analysis. For 335 patients (44%), ERCC1 status was positive (H-score exceeding 1.0, i.e. tumors with a staining intensity score of 2 and 50% or more positive nuclei or a staining intensity score of 3 and 10% or more positive nuclei). The benefit of cisplatin-based adjuvant CT was correlated with the ERCC1 status (test for interaction, P<0.009). Patients with ERCC1-negative tumors randomized to CT had significantly prolonged survival compared with patients with ERCC1-negative tumors randomized to observation (adjusted hazard ratio for death, 0.67; 95% confidence interval [0.51–0.89], P<0.006). There was no survival difference with CT among ERCC1 positive patients (adjusted hazard ratio for death, 1.18; [0.87–1.61], P=0.29). When analyzing only patients randomized to observation, the subgroup with ERCC1 positive tumors had a better survival compared to those with ERCC1 negative tumors (0.65; [0.48–0.89], P<0.008). Conclusions: Patients with completely resected NSCLC and ERCC1-negative tumors derive a substantial benefit from adjuvant cisplatin-based CT. Unrestricted grants: Eli-Lilly, PHRC, Cancéropôle Rhône-Alpes, Austrian Science Fund No significant financial relationships to disclose.
A phase II trial of ZD6474 plus docetaxel in patients with previously treated NSCLC: Follow-up results
Authors: Heymach J. V. , Johnson B. E. , Prager D. , Csada E. , Roubec J. , Pesek M. , Spasova I. , Hou J. , Kennedy S. , Herbst R. S. 
Published: March 2020

7016 Background: ZD6474, a once-daily oral agent, targets key signaling pathways in cancer by inhibiting VEGF, EGF and RET receptor tyrosine kinases. ZD6474 in combination with docetaxel (Doc) was assessed in patients (pts) with refractory non-small-cell lung cancer (NSCLC). Methods: Pts eligible for this randomized, double-blind study had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of 1st-line platinum-based chemotherapy. The primary objective was to determine whether once-daily oral ZD6474 (100 or 300 mg) + Doc (75 mg/m2 i.v. infusion every 21 days) prolonged progression-free survival (PFS) vs Doc alone (80% power to detect 50% prolongation at P<0.2). Overall survival was a secondary objective. Results: A total of 127 pts (73 male/54 female; median age 59 yrs, range 29–82) received ZD6474 100 mg + Doc (n=42), ZD6474 300 mg + Doc (n=44) or Doc (n=41). The study met its primary objective of PFS prolongation with the addition of ZD6474: median PFS was 19 wks for ZD6474 100 mg + Doc (HR=0.64; P=0.074); 17 wks for ZD6474 300 mg + Doc (HR=0.83; P=0.461); and 12 wks for Doc. A total of 64 pts (50%) presented with histology other than adenocarcinoma, including 37 with squamous, and 13 pts (10%) entered with CNS metastases. Exploratory subgroup analyses suggest advantages in PFS for ZD6474 + Doc vs Doc both for adenocarcinoma and for other lung cancer histologies. Common adverse events (AEs) included diarrhea, rash and asymptomatic QTc prolongation, all responded to standard management or dose interruption/reduction. Four pts with squamous experienced hemoptysis (ZD6474 100 mg + Doc, n=2 CTC grade 1/2; Doc, n=2 CTC grade 3/4). No fatal episodes of hemoptysis or any CNS hemorrhage AEs were reported in pts receiving ZD6474. Overall survival data were immature at the time of PFS analysis, and a mature survival analysis will be conducted at ∼75% of deaths (anticipated April 2006, and will be presented at the meeting). As of December 2005, 40/127 (31%) pts were alive, 5 of whom continue to receive ZD6474. The minimum follow-up of pts still alive was 17 months. Conclusions: ZD6474 + Doc prolonged PFS vs Doc alone, and these promising data have led to the initiation of Phase III evaluation of ZD6474 + Doc in 2nd-line NSCLC. [Table: see text]
Multi-center, double-blind, randomized, placebo-controlled phase II study to assess the efficacy of recombinant MAGE-A3 vaccine as adjuvant therapy in stage IB/II MAGE-A3-positive, completely resected, non-small cell lung cancer (NSCLC)
Authors: Vansteenkiste J. , Zielinski M. , Dahabre J. , Linder A. , Malinowski W. , Jassem J. , Lopez-Brea M. , Passlick B. , Lehmann F. , Brichard V. 
Published: March 2020

7019 Background: About half of the patients with completely resected early-stage NSCLC will relapse. Adjuvant chemotherapy reduces the number of relapses at the expense of substantial toxicity. Activity of MAGE-A3 vaccination (i.e. recombinant MAGE-A3 protein and a potent GSK immunological adjuvant) has been proven in advanced melanoma. As about 35% of NSCLCs express the MAGE-A3 antigen, post-operative MAGE-A3 vaccination may be a targeted, well tolerated, and effective adjuvant therapy. Methods: Patients with completely resected, MAGE-A3 positive (assessed by quantitative RT-PCR), stage pIB or pII were 2:1, double-blind, randomly assigned to postoperative MAGE-A3 vaccination or placebo. Vaccination was started ≥6 weeks after surgery, with 5 vaccinations at 3-week intervals, followed by 8 vaccinations every 3 months. Randomization was stratified for stage (IB vs. II), histology (squamous vs. other), and lymph node procedure (sampling vs. dissection). Other anti-cancer adjuvant therapy was not allowed. Primary endpoint was time-to-recurrence, other endpoints were recurrence rates at different times, and survival. A sample size of 180 patients (120 active, 60 placebo) was chosen, to achieve 48% power (α=10%) to detect a 10% difference, assuming a 40% recurrence rate at month 30 in the placebo group (log rank test). A thorough interim efficacy analysis by an independent statistician (blinded to investigators and sponsor) is planned for 18 months after completion of recruitment. Results: 35% of 1,089 biopsies from 59 sites were MAGE-A3 positive. In two years, 182 patients were randomized (121 stage IB, 61 stage II). Overall, treatment was well tolerated, with high protocol compliance. Data collection for the interim efficacy analysis was initiated on December 19th, 2005. Median follow-up was 21 months, with 62 recurrences recorded. Conclusions: This study confirms expression of MAGE-A3 antigen in 35% of early NSCLC cases, and demonstrates good tolerability of postoperative MAGE-A3 vaccination. Efficacy results of the interim analysis will be available in February 2006. [Table: see text]